Pediatric Board Study Guide A Last Minute Review, 2nd Edition 2020

Osama I.
Naga
Editor
Pediatric Board
Study Guide
A Last Minute Review
Second Edition
123
Pediatric Board Study Guide
Osama I. Naga
Editor
Pediatric Board Study Guide

A Last Minute Review
Second Edition
With Best Regards

Dr. Alhaytham Dahdal
MBBS, MRCPCH UK, PABHS, PSCMS
Paediatric Senior Registrar
KSAFHNWR – Tabuk – KSA
For more books :
Alhaytham59@yahoo.com
nwafhpaededuc@gmail.com
Editor
Osama I. Naga, MD
Department of Pediatrics
Paul L. Foster School of Medicine
Texas Tech University Health Sciences Center
El Paso, TX
USA
ISBN 978-3-030-21266-7 ISBN 978-3-030-21267-4 (eBook)

https://doi.org/10.1007/978-3-030-21267-4
© Springer Nature Switzerland AG 2020

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is
concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction
on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation,
computer software, or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not
imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and
regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed
to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty,
expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been
made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
I owe my deepest gratitude to the contributors whose expertise
helped bring this pediatric resource to life.
To all the pediatricians who keep on learning for the sake

of the children!
Preface
The Pediatric Board Study Guide: A Last Minute Review provides the core material needed to
pass the General Pediatrics Certifying Examination by the American Board of Pediatrics
(ABP) and to meet the requirements required for the ABP Maintenance of Certification. This
book contains a total of 33 chapters; the first 31 chapters discuss all aspects of pediatric medi-
cine and are all updated according to the most recent content specifications provided by the
ABP. Chapter 32 reviews common pediatric radiology cases, while Chapter 33, the final chap-
ter, consists of high-yield last minute review cases.
The second edition is notably more comprehensive and detailed than the first. Improvements
over the previous edition include more illustrations and added chapters. Each chapter has been
either written or reviewed by an expert in that specific field from a top academic institution in
the United States. New chapters include Sports Medicine, Nutrition, Fluids and Electrolytes,
Ethics, Patient Safety and Quality Improvement, and Pharmacology. Finally, to make the chap-
ters even more incisive, “Pearls and Pitfalls” have been added at the end of each chapter.
The 80 clinical case scenarios in the Radiology Review (Chap. 32), with its distinct images
and radiological findings, should not only improve exam performance but also help the general
pediatrician to identify common radiological findings.
The final chapter, Last Minute Review, has been expanded in this new edition. These high-
yield cases are arranged in the same sequence as the book chapters and placed in a way that
allows the reader to discriminate among diseases and conditions, helping the test taker to dis-
tinguish between similar presenting cases on the exam. The final chapter allows the reader to
review in the shortest time possible more than 1700 critical facts for the pediatric board exam,
making it the ideal resource for the week prior to the exam.
This book is of particular interest to pediatricians, fellows, pediatric subspecialists prepar-
ing for the board examination or certification maintenance, pediatric residents preparing for
the in-service exam, daily rounds, and real-life clinical encounters.
About the ABP board-certifying exam

• The board exam is offered once a year, usually in October.
• The exam consists of four sections.
• There is a total of 330–350 multiple-choice questions with normally five answer choices for
each question.
• There are currently four sections with each section lasting 105 minutes. There is a 15-minute
break between the first two sections.
• After the second section, there is a 60-minute lunch break.
• There is another 15-minute break between section 3 and section 4
• The exam is scored from 0 to 300 with 180 being a passing score.
How to study for the ABP board-certifying exam

• Read the text of the Pediatric Board Study Guide: A Last Minute Review thoroughly mul-
tiple times throughout your residency.
• Chapters can be read sequentially or can be read in conjunction with a rotation.
vii
viii Preface
• For example, a resident doing a 1-month pediatric cardiology rotation could usefully read
in Chap. 19, Cardiology.
• After finishing a chapter, turn to Chap. 33 to review the Last Minute Review cases for that
particular specialty.
• Make sure to study the most recent self-assessment curricula of the Pediatric Review and
Education Program (PREP): https://shop.aap.org/professional-education/self-assessments.
• Simulate the test-taking experience by answering timed questions.
• Read the critiques/explanations after each question, including the PREP Pearls at the end of
each question.
• Read the new articles in Pediatrics in Review and answer their CME questions.
• Two to three months before the exam, read the Pediatric Board Study Guide one more time.
• One week before the exam, read for one final time Chap. 33, the Last Minute Review.
• Rest at least 24 hours before the exam.
The day of the exam

• Have a good breakfast.
• Arrive early to the testing center.
• Make sure to have all the documents with you (ID, exam ticket, etc.).
• Make sure to dress appropriately; sometimes the testing room may be cold.
• During the exam, make sure to answer all questions. Do not leave any question unanswered
even if you do not know the answer. There is no penalty for guessing.
• Pace yourself: once the time has expired in a section, you cannot go back.
El Paso, TX, USA Osama Naga

Contents
1 General Pediatrics�� 1

Osama I. Naga
2 Neonatology�� 35
Mamta Fuloria
3 Adolescent Medicine�� 81
Jessica Addison
4 Genetic Disorders�� 103
Golder N. Wilson, Osama I. Naga, and Vijay S. Tonk
5 Metabolic Disorders�� 143
Osama I. Naga
6 Mental and Behavioral Health�� 167
Mohamed Hamdy Ataalla
7 Emergency Medicine �� 197
Jo-Ann O. Nesiama, Jennifer McConnell, and Kenneth Yen
8 Critical Care �� 247
Manpreet K. Virk and M. Hossein Tcharmtchi
9 Infectious Diseases �� 267
Matthew B. Laurens
10 Hematology/Oncology�� 345
Arpan A. Sinha, Scott Moerdler, Ellen Fraint, Adit Tal, Nora E. Rahmani, and
Kerry Morrone
11 Allergy and Immunology�� 391
Maria I. Garcia Lloret and Caroline Y. Kuo
12 Endocrinology�� 417
Amr Morsi
13 Orthopedics�� 465
Amr Abdelgawad and Marwa Abdou
14 Sports Medicine�� 507
Daniel Murphy
15 Rheumatology�� 525
Amanda G. Brown, William Blaine Lapin, Andrea A. Ramirez, and Jennifer L.
Rammel
16 Neurology�� 551
Ivet Hartonian, Jong W. Yoo, and Jason T. Lerner
ix
x Contents
17 Ophthalmology�� 585
Kyle E. Miller and Shira L. Robbins
18 Ear, Nose, and Throat�� 611
Kara D. Meister and Anna H. Messner
19 Cardiology�� 643
Grace Kung, Allison Hill, and Jennifer Su
20 Pulmonology �� 691
Tanya Martínez-Fernández, Yadira Rivera-Sánchez, and Preeti Sharma
21 Nutrition�� 731
Susan S. Baker
22 Gastroenterology�� 757
Robert D. Baker
23 Nephrology�� 799
Beatrice Goilav
24 Fluids and Electrolytes�� 825
Benjamin Steinman and Beatrice Goilav
25 Urology�� 841
Catherine J. Chen and Micah A. Jacobs
26 Dermatology �� 855
Megan Craddock and Jennifer Ruth
27 Psychosocial Issues and Child Abuse �� 887
Sitratullah O. Kukoyi-Maiyegun
28 Ethics�� 903
Marwa Abdou
29 Research and Statistics�� 913
30 Patient Safety and Quality Improvement�� 921
Osama I. Naga
31 Pharmacology and Pain Management �� 927
Osama I. Naga
32 Radiology Review�� 947
Wendy G. Kim and Michael George
33 Last-Minute Review�� 1015
Osama I. Naga
Index�� 1137
Editor
Osama I. Naga, MD Department of Pediatrics, Paul L. Foster School of Medicine, Texas
Tech University Health Sciences Center, El Paso, TX, USA
xi
Contributors
Amr Abdelgawad, MD, MBA Department of Orthopaedic Surgery and Rehabilitation, Texas

Marwa Abdou, MD Department of Pediatrics, Texas Tech University Health Sciences Center,
El Paso, TX, USA
Jessica Addison, MD, MS Division of Adolescent/Young Adult Medicine, Department of
Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
Mohamed Hamdy Ataalla, MD Department of Child and Adolescent Psychiatry, Texas Tech
University Health Sciences Center, El Paso, TX, USA
Robert D. Baker, MD, PhD Department of Pediatrics, Jacobs School of Medicine and
Biomedical Sciences, University at Buffalo, State University of New York, Amherst, NY, USA
Susan S. Baker, MD, PhD Jacobs School of Medicine and Biomedical Sciences, University
at Buffalo, State University of New York, Buffalo, NY, USA
Amanda G. Brown, MD Division of Rheumatology, Department of Pediatrics, Baylor
College of Medicine, Houston, TX, USA
Catherine J. Chen, MD Department of Urology, University of Texas Southwestern Medical
Center, Dallas, TX, USA
Megan Craddock, MD Department of Dermatology and Pediatrics, Texas Children’s
Hospital, Baylor College of Medicine, Houston, TX, USA
Ellen Fraint, MD Division of Pediatric Hematology, Oncology, Marrow and Blood Cell
Transplantation, Department of Pediatrics, Children’s Hospital at Montefiore, Bronx, NY,
USA
Mamta Fuloria, MD Division of Neonatology, Department of Pediatrics, The Children’s
Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
Maria I. Garcia Lloret, MD, MSc Division of Pediatric Allergy/Immunology and
Rheumatology, Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA
Michael George, MD Department of Radiology, Boston Children’s Hospital, Harvard
Medical School, Boston, MA, USA
Beatrice Goilav, MD Pediatric Nephrology, Children’s Hospital at Montefiore, Albert
Einstein College of Medicine, Bronx, NY, USA
Ivet Hartonian, MD, MS Pediatric Neurology, Department of Pediatrics, Adventist Health
White Memorial, Los Angeles, CA, USA
Allison Hill, MD Division of Cardiology, Department of Pediatrics, Children’s Hospital of
Los Angeles, USC Keck School of Medicine, Los Angeles, CA, USA
xiii
xiv Contributors
Micah A. Jacobs, MD, MPH Department of Urology, University of Texas Southwestern

Medical Center, Dallas, TX, USA
Wendy G. Kim, MD Department of Radiology, Boston Children’s Hospital, Harvard Medical
School, Boston, MA, USA
Sitratullah O. Kukoyi-Maiyegun, MD Department of Pediatrics, Paul L. Foster School of
Medicine, Texas Tech University Health Science Center, El Paso, TX, USA
Grace Kung, MD Division of Cardiology, Department of Pediatrics, Children’s Hospital of
Caroline Y. Kuo, MD Division of Pediatric Allergy/Immunology and Rheumatology,
Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA
William Blaine Lapin, MD Division of Rheumatology, Department of Pediatrics, Baylor
Matthew B. Laurens, MD, MPH Division of Infectious Diseases and Tropical Pediatrics,
Department of Pediatrics, Center for Vaccine Development and Global Health, University of
Maryland School of Medicine, Baltimore, MD, USA
Jason T. Lerner, MD Pediatric Neurology, Department of Pediatrics, UCLA Mattel Children’s
Hospital, Los Angeles, CA, USA
Tanya Martínez-Fernández, MD Division Respiratory Medicine, Department of Pediatrics,
University of Texas Southwestern Medical Center/Children’s Medical Center Dallas, Dallas,
TX, USA
Jennifer McConnell, MD Division of Pediatric Emergency Medicine, Department of
Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA
Kara D. Meister, MD Department of Otolaryngology-Head & Neck Surgery, Pediatrics
Division, Lucile Packard Children’s Hospital, Stanford University, Stanford, CA, USA
Anna H. Messner, MD, FACS, FAAP Professor of Otolaryngology/Head & Neck Surgery,
Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA
Kyle E. Miller, MC(FS) USN, MD Department of Ophthalmology, Naval Medical Center
Portsmouth, Portsmouth, VA, USA
Scott Moerdler, MD Pediatric Hematology/Oncology Program, Department of Pediatrics,
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers
University, New Brunswick, NJ, USA
Kerry Morrone, MD Division of Pediatric Hematology, Oncology, Marrow and Blood Cell
USA
Amr Morsi, MD Division of Endocrinology, Department of Pediatrics, UPMC Children’s
Hospital of Pittsburgh, Pittsburgh, PA, USA
Daniel Murphy, MD, CAQ-Sports Medicine Department of Family and Community
Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Center, El Paso,
TX, USA
Osama I. Naga, MD Department of Pediatrics, Paul L. Foster School of Medicine, Texas
Contributors xv
Jo-Ann O. Nesiama, MD, MS Division of Pediatric Emergency Medicine, Department of

Violeta Radenovich, MD, MPH Children’s Eye Center of El Paso, Pediatric Ophthalmology,
Texas Tech University Health Science Center, El Paso, TX, USA
Nora E. Rahmani, MD Division of Pediatric Hematology, Oncology, Marrow and Blood
Cell Transplantation, Department of Pediatrics, Children’s Hospital at Montefiore, Bronx, NY,
USA
Andrea A. Ramirez, MD Division of Rheumatology, Department of Pediatrics, Baylor
Jennifer L. Rammel, MD Division of Rheumatology, Department of Pediatrics, Baylor
Yadira Rivera-Sánchez, MD Division Respiratory Medicine, Department of Pediatrics,
University of Texas Southwestern Medical Center/Children’s Medical Center Dallas, Dallas,
TX, USA
Shira L. Robbins, MD, FAAO, FAAP Department of Ophthalmology, Ratner Children’s Eye
Center, University of California San Diego, La Jolla, CA, USA
Jennifer Ruth, MD Department of Dermatology and Pediatrics, Dell Children’s Medical
Group, Austin, TX, USA
Preeti Sharma, MD Division Respiratory Medicine, Department of Pediatrics, University of
Texas Southwestern Medical Center/Children’s Medical Center Dallas, Dallas, TX, USA
Arpan A. Sinha, MBBS, MD Jimmy Everest Center of Pediatric Hematology and Oncology,
Department of Pediatrics, The University of Oklahoma Health Sciences Center, Oklahoma
City, OK, USA
Benjamin Steinman, DO Department of Pediatrics, The Children’s Hospital at SUNY
Downstate, SUNY Downstate Medical Center, Brooklyn, NY, USA
Jennifer Su, MD Division of Cardiology, Department of Pediatrics, Children’s Hospital of
Adit Tal, MD Division of Pediatric Hematology, Oncology, Marrow and Blood Cell
USA
Hina J. Talib, MD Division of Adolescent Medicine, Department of Pediatrics, Children’s
Hospital at Montefiore, Bronx, NY, USA
M. Hossein Tcharmtchi, MD Department of Pediatrics, Section of Critical Care, Baylor
College of Medicine, Texas Children's Hospital, Houston, TX, USA
Vijay S. Tonk, PhD Department of Pediatrics, Texas Tech University Health Sciences Center,
Lubbock, TX, USA
Manpreet K. Virk, MD Department of Pediatrics, Section of Critical Care, Baylor College
of Medicine, Texas Children’s Hospital, Houston, TX, USA
Dawn M. Wahezi, MD, MS Pediatric Rheumatology, Children’s Hospital at Montefiore,
Bronx, NY, USA
Golder N. Wilson, MD, PhD Department of Pediatrics, Texas Tech University Health
Sciences Center and KinderGenome Medical Genetics, Dallas, TX, USA
xvi Contributors
Kenneth Yen, MD, MS Division of Pediatric Emergency Medicine, Department of Pediatrics,

UT Southwestern Medical Center, Dallas, TX, USA
Jong W. Yoo, MD Pediatric Neurology, Department of Pediatrics, UCLA Mattel Children’s
Hospital, Los Angeles, CA, USA
Mohamed A. Zebda, DO, MPH Department of Pediatrics, Paul L. Foster School of Medicine,
Texas Tech University Health Sciences Center, Galveston, TX, USA
General Pediatrics
1
Osama I. Naga
GROWTH • 3–6 months: weight gain is approximately

15 g/day
Background • 6–12 months: weight gain is approximately
• Growth is affected by maternal nutrition and 10 g/day
uterine size • Birth weight is expected to double by
• Genetic growth potential is inherited from 5–6 months
parents and also depends on nutrition through-
out childhood Height [1]
• Growth is affected by growth hormone, thy- • The height of a newborn increases by 50% or
roid hormone, insulin, and sex hormones, all by 25.4 cm (10 in.) in the 1st year
of which have varying influence at different • The height of a newborn doubles within
stages of growth 3–4 years
• Deviation from normally expected patterns of • After 2 years the height increases by an aver-
growth often can be the first indication of an age 5–6 cm/year
underlying disorder • There is a range of pubertal peak growth
• Carefully documented growth charts serve as velocities of around 7–12 cm per year in boys
powerful tools for monitoring the overall and 6–10.5 cm per year in girls
health and well-being of patients
Measurements [2]
• Key to diagnosing abnormal growth is the
• The length or supine height should be mea-
understanding of normal growth, which can
sured in infants and toddlers < 2 years
be classified into 4 primary areas: fetal, post-
• Standing heights should be used if age
natal/infant, childhood, and pubertal
> 3 years
Weight • For children between 2 and 3 years of age, it is
• Healthy term infants may lose up to 10% of best to measure both supine length and stand-
birth weight within the first 10 days after birth ing height and compare the 2 measurements
• Newborns quickly regain this weight by • Plot gestational age rather than chronological
2 weeks of age age for preterm infants
• 0–3 months: weight gain is approximately • Specific growth charts are available for special
30 g/day populations, e.g., trisomy 21, Turner syndrome,
Klinefelter syndrome, and achondroplasia
O. I. Naga (*)
Department of Pediatrics, Paul L. Foster School of Medicine,
Texas Tech University Health Sciences Center, El Paso, TX, USA
e-mail: osama.naga@ttuhsc.edu
© Springer Nature Switzerland AG 2020 1

O. I. Naga (ed.), Pediatric Board Study Guide, https://doi.org/10.1007/978-3-030-21267-4_1
2 O. I. Naga
Head circumference Table 1.1 Difference between benign familial macroceph-

• Head circumference will increase by 12.7 cm aly and hydrocephalus
(5 in.) in the 1st year Benign familial
macrocephaly Hydrocephalus
Growth curve reading Family history of History of prematurity, IVH,
macrocephaly trauma, or CNS infection
• Shifts across 2 or more percentile lines may
Normal growth and Spasticity, gait disturbance,
indicate an abnormality in growth development cognitive deterioration,
• Weight loss is one of the first signs of malab- hypertonia
sorption and of cases of malnourishment or No signs of increased Bulging AF, ocular globes deviate
neglect ICP downward (sun-setting sign),
headaches, vomiting, irritability
• Primary linear growth problems often have
Reassurance Referral to neurosurgeon
some congenital, genetic, or endocrine
CNS Central nervous system, IVH Intraventricular hemor-
abnormalities (see also Chap. 12 rhage, ICP Intracranial pressure, AF Anterior fontanelle
Endocrinology)
• Genetic channeling: downward percentile
–– Full history, including prenatal, birth, past
crossing of a large baby born to short parents
medical, and family
or upward percentile crossing of a small baby
–– Head ultrasound is the study of choice if
born to tall parents typically accomplished by
anterior fontanelle is still open
9–12 months
–– Skull radiography
–– Brain magnetic resonance imaging (MRI)
if the anterior fontanelle is closed
Macrocephaly
Hydrocephalus (see Table 1.1)
Definition
• Head circumference 2 standard deviations above • Referral to a pediatric neurosurgeon
the mean
Causes icrocephaly (See Also Chap. 16

M
• Benign familial macrocephaly with enlarge- Neurology)
ment of subarachnoid space
• Hydrocephalus Definition
• Intracranial hemorrhage or mass • Head circumference 2 standard deviations
• Genetic causes e.g., Soto syndrome, or below the mean
“cerebral gigantism”
Causes
Benign familial macrocephaly (Table 1.1) • Congenital infections, e.g., TORCH (Toxo
• Most common cause (50%) plasmosis, Others, Rubella, Cytomegalovirus
• Autosomal dominant; usually seen in one or [CMV]), Herpes simplex), Zika virus
both parents • Maternal deprivation (folate deficiency, mal-
• Document parental head size nutrition, hypothyroidism)
• Reassure parents and child if child’s head size • Maternal hyperphenylalaninemia
is congruent with familial sizes • Toxic or metabolic disorders
• Periodic monitoring of the head size • Genetic conditions, e.g., trisomy 21, Cornelia
• Periodic monitoring of physical growth and de Lange syndrome
neurological development • Acquired or postnatal onset of microcephaly,
• If the child’s head size is not congruent with e.g., hypoxic-ischemic encephalopathy
familial sizes:
1 General Pediatrics 3
Plagiocephaly (Fig. 1.1) [3] • If more than one suture is involved, it is com-

monly associated with genetic disorders
Background • Asymmetric skull (head growth is limited in
• Deformational flattening from lack of changes the plane perpendicular to the fused suture)
in head positions is the most common cause • Bony ridging overlying the fused suture
of asymmetric head shape • Commonly associated with an increase in
Causes head size asymmetrically
• Positional or supine sleeping is the most com- • Scaphocephaly (elongated head) is the most
mon cause of plagiocephaly common type of craniosynostosis, due to
• Causes of persistent head tilt, e.g., congenital early fusion of the sagittal suture; ridging of
muscular torticollis, ocular torticollis, the sagittal suture is palpable
Klippel-Feil syndrome (See also Chap. 13
Orthopedics.) Secondary craniosynostosis
• Craniosynostosis • Primary failure of brain growth leads to early
fusion of sutures and microcephaly
Craniosynostosis (See Also Chap. 4 Genetic
Disorders) Deformational plagiocephaly (Fig. 1.2, Table 1.2)
• Anterior displacement of the occiput and the
Primary craniosynostosis frontal region on the same side (parallelogram)
• One or more sutures fuse prematurely while • Ear position is more anterior on the side of
the brain still increasing in size flattening in positional plagiocephaly
• If one suture is involved, it is usually isolated • Supine sleeping recommendations (“baby on
back”) have increased the prevalence of pos-
terior plagiocephaly
Diagnosis
• Neonatal examination to exclude syndromes
with cranial and brain anomalies
• Careful examination alone can make the
diagnosis
• Referral to a pediatric neurosurgeon if cranio-
synostosis is clinically suspected
• Plain skull radiography or CT scan can con-
firm the diagnosis of craniosynostosis if the
diagnosis is not clear
• Cranial CT scan with 3-dimensional recon-
struction is not required to make the diagno-
sis of craniosynostosis in most cases
Treatment
• Deformational plagiocephaly
–– Observation; usually resolves spontaneously
–– The helmet may be beneficial in severe
Fig. 1.1 A 5-month-old-boy with deformational plagio- cases of deformational plagiocephaly
cephaly, flattening on the left side, and ipsilateral frontal
bossing
4 O. I. Naga
a b
Fig. 1.2 (a) Deformational plagiocephaly; (b) Unilambdoid synostosis
Table 1.2 Difference between deformational plagiocephaly DEVELOPMENTAL MILESTONES

and plagiocephaly due to unilambdoid synostosis
Deformational Plagiocephaly due to
[4, 5]
plagiocephaly unilambdoid synostosis
Parallelogram-shaped Trapezoid-shaped head The American Academy of Pediatrics (AAP) rec-
head ommends that clinicians screen children for gen-
Occipital flattening on Occipital flattening on one side eral development using standardized, validated
one side tools at 9, 18, and 30 months and for autism at 18
Frontal bossing on the Frontal bossing on the
same side contralateral side
and 24 months or at any point when a caregiver or
Anterior displacement of Posterior displacement of the the clinician has a concern
the ear on the same side ear on the same side
Palpable suture, no Tools for screening
Absence of suture or palpable
palpable ridging ridging of fused lambdoid • Denver Developmental Screening Test
suture • Ages & Stages Questionnaires (ASQs)
• Modified Checklist for Autism in Toddlers
–– Treatment of underlying causes, e.g., con- (M-CHAT)
genital muscular torticollis or other causes
of head tilt
–– Emphasis on floor (“tummy”) time, occu- Newborn
pational/physical therapy
• Craniosynostosis Gross motor
–– Surgery, usually between 6 and 12 months • Lies in flexed position
• Turns head from side to side; head sags on • Begins to push up when lying on tummy
ventral suspension • Head lags when pulled to sitting position
Social/communication Fine motor

• Visual preference for human face • Hands unfisted 50% of the time
• Retains an object or finger if placed in the
Visual hand
• Able to fixate face on light in line of vision; • Brings hands to mouth, sucks on hand, and
“doll’s-eye” movement of eyes on turning the may hold hands together
body
• Responds to visual threats by blinking Social/communication/problem solving
• Visual acuity is 20/400 • Follows moving object 180°
Reflex • Able to fixate on the face and follow it briefly
• Moro, stepping, placing, and grasp reflexes • Tries to look at parents
are all active • Stares momentarily where object disappeared
• Smiles on social contact; listen to voice and
coos
1 Month • Turns toward sounds
Gross motor Language
• Legs more extended • Coos and makes gurgling sounds
• Head lifted momentarily to plane of body on • Begins to act bored (crying, fussy)
ventral suspension
• Chin up in the prone position
• Turns head in the supine position 3 Months
Fine motor Gross motor
• Hands fisted near the face • Lifts head and chest with arms in prone
• Sucks well position
• May roll to the side
Social/communication/problem-solving
• Begins to smile Fine motor
• Gazes at black-white objects • Brings hands together in the midline and to
• Watches person; follows moving object the mouth
• Body movements following the sound of • Inspects their own fingers
others • Bats at objects or toys
Language Social/communication/problem solving

• Startles to voice or sound • Follows parents across the room
• Expression of dislike for a taste or a loud
sound
2 Months • Regards hands and toys
Gross motor Language
• Raises head slightly farther in prone position • Regards and vocalizes to parents when
• Head sustained in plane of body on ventral talking
suspension • Chuckles
6 O. I. Naga
4 Months • Pushes down on legs when feet are on a hard

surface
Gross motor
• Holds head steady and no head lag when Fine motor
pulled from lying down to sitting position • Brings hands to mouth
(Fig. 1.3) • Uses hands and eyes together, such as seeing
• May be able to roll over from front to back a toy and reaching for it
• Pushes tummy, with elbows lifting the head • Shakes rattle
and chest (Fig. 1.4)
Social/communication/problem solving
• Responds to affection
• Begins to babble
• Laughs out loud
• Excited at sight of a bottle
• Recognizes familiar people and things at a
distance
• Likes to play with people and might cry when
playing stops
Language
• Vocalizes when alone
Reflexes
• Asymmetric tonic reflex is gone
• Palmar grasp is gone
6 Months
Gross motor
Fig. 1.3 Holds head steady and no head lag when pulled
from lying down to sitting position • Begins to sit with minimal support
• Rolls over from back to front and front to
back
• Supports weight on legs and might bounce
Fine motor
• Transfers objects from one hand to another
• Brings objects or food to the mouth
• Places hands on the bottle
• Bangs and shakes toys
• Rakes pellets
• Removes cloth on face
• Stranger anxiety
• Responds to own name
• Responds to sounds by making sounds show-
Fig. 1.4 Developmental milestone at 4 months: Pushes
tummy, with elbows lifting the head and chest ing joy and displeasure
Language • Attends to sounds and music

• Monosyllabic babble • Prefers mother
• Looks at self in mirror and smiles • Inhibits to “no”
Language
7 Months • More vowels and more variety of sounds
Gross motor 9 Months

• Sits steady without support (Fig. 1.5)
• Bounces when held upright Gross motor
• Puts arms out to the side for balance • Can get into sitting position from lying down
• Pulls to stand
Fine motor • Begins to crawl (Fig. 1.6)
• Radial palmar grasp • Bears walk with all limbs straight
Social/communication/problem-solving Fine motor
• Explores different aspects of toy and observes • Radial-digital grasps of a block
toy block in each hand • Bangs 2 blocks together
• Finds partially hidden toys or objects • Bites and chews cookie
• Looks from object to parents and back when • Inspects and rings a bell
wanting help • Pulls string to obtain a ring
• Looks at familial objects or toys
• Separation anxiety
• Recognizes familiar people
• May be afraid of strangers
Fig. 1.5 Developmental milestone at 7 months: Sits steady Fig. 1.6 Developmental milestone at 9 months: Begins to
without support crawl
8 O. I. Naga
• Uses sound to get attention

• Plays peek-a-boo
• Orients to name well
Language
• Says “mamama” and “bababa” nonspecific
• Copies sounds and gestures of others
12 Months
Gross motor
• Walks with one hand held
• Pulls up to stand, walks holding on to furni-
ture (“cruising”)
• May stand alone and make a few steps with-
out holding (Fig. 1.7)
Fine motor
• Fine pincer grasps of pellet
• Holds crayon and scribbles after
demonstration
• Attempts tower of 2 blocks
• Finger feeds part of a meal
• Takes off a hat
• Puts out arm or leg to help with dressing
• Rattles spoon in a cup
• Puts a toy in a container, takes it out of the
container
• Shows parents object to share interest
• Follows one-step command with a gesture
• Looks at the right picture or thing when it is
named Fig. 1.7 Developmental milestone at 12 months: May stand
• Points to get desired object (proto-imperative alone and make a few steps without holding
pointing) and to share interest
• Uses several gestures when vocalizing (e.g., 14 Months
waving, reaching)
Language Gross motor
• Says a few words, including “mama,” “dada,” • Walks well
and exclamations like “uh-oh!” • Stands without pulling
Fine motor • Gets an object from another room upon

• Imitates back and forth scribbling demand
• May add the third block to a 2-block tower
• Puts round peg in and out of a hole Language
• Removes socks and shoes • Uses 3–5 words
• Chews well • Mature jargoning with real words
• Puts a spoon in the mouth upside down
• Dumps pellet out of a bottle after a
demonstration 8 Months
1
Social/communication/problem-solving Gross motor

• Points at an object to express interest (proto- • Runs well
declarative pointing) • Creeps downstairs
• Purposeful exploration of toys through trial • Gets onto a chair without assistance
and error
Fine motor
• Follows one-step commands without gesture
• Throws a ball while standing
Language • Makes 4-block tower
• Names one object • Imitates vertical stroke
• Can help undress him/herself
• Eats with a spoon
15 Months • Matches pairs of objects
Gross motor Social/communication/problem-solving

• Stoops to pick up an object from the floor • Normal M-CHAT
• Runs stiff-legged • Plays simple pretend, such as feeding a doll
• Climbs on furniture and may be able to creep • Begins to have temper tantrum and shows
upstairs shame when does wrong
• Points to 2 of 3 objects when named and 3
Fine motor body parts
• Builds 3- to 4-block tower • Points to familiar people with the name
• Places 10 blocks in a cup • Understands “mine”
• Drinks from a cup
• Releases pellet into a bottle Language
• Eats with a spoon with some spilling • Uses 10–25 words
• Places circle in a single-shape puzzle • Imitates animal sounds
• Turns pages in a book • Names object in one picture on demand
• Hugs parents in reciprocation 4 Months
2
• Shows empathy (may cry when someone else
is crying) Gross motor
• Recognizes without demonstration that a toy • Walks upstairs and downstairs holding rail
requires activation, then hands it to an adult if • Kicks a ball
it cannot operate • Throws ball overhand
• Points to one body part • Stands on tiptoes
10 O. I. Naga
Fine motor • Knows own gender and age

• Makes a single line of blocks • Follows 3-step instructions or commands
• In drawing, imitates horizontal line • Fears imaginary things
• Begins to sort shapes and colors
• Opens door using the knob Language
• Takes off clothes without buttons • Uses words to describe what someone else is
• Pulls off pants thinking (“Dad thought I was crying”)
• Builds a tower of 6 blocks • Names body parts with function
• Parallel play • Uses 3-word sentences
• Says words like “I,” “me,” “we,” and “you”
Social/communication/problem-solving and some plurals (“cars”, “dogs,” “cats”)
• Begins to mask emotions for social etiquette • Names body parts by use
• Follows 2-step instructions or commands • 75% intelligible speech
such as “Sit on your chair and eat your food”
• Points to 5–10 objects in pictures
4 Years
Language
• Uses 2-word sentence Gross motor
• Uses 50 or more words • Balances on 1 foot for 8 seconds
• 50% intelligible speech • Hops and stands on 1 foot up to 2 seconds
Fine motor
3 Years • Throws ball overhand more than 3 yards
• Catches a bounced ball most of the time
Gross motor • Copies a square
• Walks up and down stairs, 1 foot on each step, • Goes to the toilet alone
no rails • Wipes after a bowel movement
• Climbs well • Draws man with 4 to 6 parts
• Pedals a tricycle (3-wheeled bike)
• Balances on 1 foot for 3 seconds Social/communication/problem solving
• Group play
Fine motor • Follows 3-steps commands and instructions
• Copies a circle with pencil or crayon • Tells story and accurately counts 4 pennies
• Can work toys with buttons, levers, and mov-
ing parts Language
• Screws and unscrews jar lids and turns door • Knows some basic rules of grammar, such
handle as correctly using “he,” “she,” “his,” “her”
• Understands what “2” means • 100% intelligible speech
• Imitates bridge of blocks
• Independent eating
• Puts on shoes without laces and able to unbut- 5 Years
ton clothing
Gross motor
• Draws man with 2 to 3 parts
• Walks downstairs with rail, alternating feet
Social/communication/problem-solving • Skips
• Understands long/short, big/small, more/less
Fine motor Following objects

• Copies a triangle • 1 month: Follows to the midline
• Cuts with scissors • 2 months: Follows past midline
• Builds stairs with blocks from model • 3 months: Follows 180°
• Dresses and undresses • 4 months: Circular tracking 360°
Social/communication/problem-solving Speech intelligibility

• Apologizes for mistakes • 50% intelligible at 2 years
• Draws man with 8 to 10 parts • 75% intelligible at 3 years
• Names 10 colors and counts to 10, counts 10 • 100% intelligible at 4 years
pennies correctly
Language: receptive
Language • 1 month
• Knows right from left –– Startles to voice or sound
• Asks questions about the meanings of words • 2 months
and responds to questions –– Alerts to voice or sound
• Repeats 6 to 8 words in sentences • 4 months
–– Orients head to the direction of a voice or
sound
6 Years • 8 months
–– Responds to parents
Gross motor • 9 months
• Tandem gait (heel-to-toe walks) –– Orients attentively to his or her name
• 10 months
Fine motor
–– Waves “bye-bye” in return
• Builds stairs from memory
• 12 months
• Copies a diamond shape
–– Follows one-step command with a gesture
• Writes first and the last name
• 14 months
Social/communication/problem-solving –– Follows one-step command without a gesture
• Has a best friend of same gender
Language: expressive
• Looks both ways at street when crossing
• Coos
• Draws man with 12–14 parts
–– 2 months (2–4 months)
• Able to do simple additions and subtractions
• Laughs out loud
Language –– 4 months
• Knows days of the week • Babbles
• Able to describe events in sequence –– 6 months
• “Mama” or “dada” nonspecific
–– 9 months
Key Points to Developmental • “Mama” and “dada” specific, plus a few words
Milestones –– 12 months
• Vocabulary of 10–25 words
Primitive reflexes –– 18 months
• Moro is absent around 3–4 months of age • Two-word sentences
• Palmar grasp absent around 2–3 months of age –– 2 years (18–24 months)
• Parachute starts around 6–9 months of age
12 O. I. Naga
Fig. 1.8 Fine motor

developmental milestones
and ability to draw at
different ages
16 months 18 months 2 years 3 years
4 years 41/2 years 5 years 6 years
• Three-word sentences • Smiles spontaneously at a pleasurable sight/

–– 3 years (2–3 year) sound
• Four-word sentences –– 4 months
–– 4 years (3–4 year) • Recognizes caregiver socially
–– 5 months
Drawing (Fig. 1.8) • Stranger anxiety
• Scribbles spontaneously –– 6 months
–– 16 months • Separation anxiety; gaze follows caregiver’s
• Imitates vertical lines pointing to object, “Oh, look!”
–– 18 months –– 9 months
• Imitates horizontal lines • Waves “bye-bye” in return
–– 2 years –– 10 months
• Circle • Shows objects to parents to share interests
–– 3 years –– 12 months
• Cross • Parallel play
–– 4 years –– 2 years
• Square • Reduction in separation anxiety
–– 4.5 years –– 28 months
• Triangle • Cooperative play
–– 5 years –– 3–4 years
• Diamond • Ties shoelaces
–– 6 years –– 5 years
• Distinguishes fantasy from reality
Social skills –– 6 years
• Reciprocal smiling
–– 2 months
• Follows the person who is moving across the Block play (Fig. 1.9)
room • Passes blocks
–– 3 months –– More than 6 months
15 mo 18 mo 2 years 3 years (bridge) 4 years (gate) 5 years (stairs)
Fig. 1.9 Fine motor skills and ability to use blocks at different ages
• Bangs blocks
–– 9 months
• Block in a cup
–– 12 months
• Tower 3 blocks Rake
–– 15 months
• Tower 4 blocks
–– 18 months
• Tower 6 blocks
–– 24 months
• Builds bridge with blocks
–– 3 years
Inferior pincer Fine pincer
• Builds gate with blocks
–– 4 years Fig. 1.10 Fine motor skills of catching an object at different
• Builds stairs from model ages
–– 5 years
Catching objects (Fig. 1.10) • Walks well

• Rakes –– 14 months
–– 5–6 months • Runs stiff-legged
• Radial-palmar grasp of pellet –– 15 months
–– 7–8 months • Runs well
• Inferior pincer grasp of pellet –– 18 months
–– 10 months • Kicks ball without demonstration
• Fine pincer grasp of pellet –– 2 years
–– 12 months • Skips and walks backward heel-toe
–– 5 years
Walking and running • Heel to toe walks (tandem gait)
• Independent steps –– 6 years
–– 12 months
14 O. I. Naga
Climbing stairs Table 1.4 Developmental red flags for language and social
• Creeps upstairs skills by age [4]
–– 15 months Age Language and social red flags
• Creeps downstairs Newborn Does not respond to loud sounds
2 months Does not alert to voice, lack of looking at faces
–– 18 months Does not watch things as they move
• Walks downstairs holding rail, both feet on 4 months Does not coo or make sounds
each step Does not smile at people
–– 2 years 6 months Does not turn toward sounds; no smiling,
• Goes up stairs, alternating feet, no rail laughing, or expression
9 months Does not babble (“mama,” “baba,” “dada”)
–– 3 years 12 Does not respond to name
• Walks downstairs with rail, alternating feet months Does not understand “no”
–– 5 years Indifferent or resistant attachment to the
Developmental red flags (Tables 1.3 and 1.4) [4] caregiver
Does not look where caregiver points
15 Does not use words “mama,” “papa,” “dada”
months Does not point to the desired object
Table 1.3 Developmental red flags for motor skills by 18 Does not gain new words
age [4] months Does not have at least 6 words
Age Motor red flags Does not point to show things to other or share
Newborn Hypotonia and feeding difficulty interest
2 months Unable to hold head up when pushing up 24 Unable to use two-word phrases (e.g., “drink
when on tummy months water”)
4 months Unable to hold head steady Unable to follow simple instructions
Unable to bring things to the mouth Unable to imitate actions or words
Persistent fisting (a predictor of Unable to maintain eye contact
neurological dysfunction) 36 Unable to use a three-word sentence
6 months Unable to pass an object from one hand to months Unable to pretend, play, or make-believe
another and does not try to reach an object 4 years Unable to speak clearly
Floppy like a rag doll Unable to answer simple questions
9 months Unable to sit, not rolling Unable to use pronouns (“I”, “me”, “you”,
12 months Unable to stand or bear weight on legs “he”, and “she”) correctly
when supported Ignores other children or does not respond to
Unable to crawl people outside the family
15 months Unable to do pincer grasps 5 years Unable to use plurals or past tense properly
18 months Unable to walk Unable to recognize shapes, letters, colors
24 months Unable to walk well Unable to brush teeth, use toilet, wash and dry
36 months Unable to climb stairs well and frequent hands, or get undressed without help
falling Unable to distinguish between reality and
4 years Unable to jump in place fantasy
5 years Unable to draw pictures, a cross, or a Shows extreme behavior (unusually fearful,
square aggressive, shy, or sad)
Poor balance 6–12 Unable retell or summarize a story
6–12 years Unable to skip or hop on one foot years Unable to name friends
Unable to write name Unable to recognize the feelings of others
All ages Loss of skills they once had All ages Loss of skills they once had
IMMUNIZATION [6, 7] –– Compare the risks of vaccines to the risks

of diseases they protect against, some of
(TABLE 1.5)
which can cause death or permanent
Responding to parents who refuse immuniza- disability
tion for their children • Refer parents to reputable sources and data-
• Listen to parents and address all their con- base about vaccines
cerns about vaccines • Discuss risks and benefits in each subsequent
• Explain all risks and benefits of the visit along with proper documentation
vaccinations: • Unimmunized children may be prevented
–– Unimmunized, delay in vaccination, and from attending schools during outbreaks of
use of alternative immunization schedules vaccine-preventable diseases
have caused a resurgence of many infec- • Advise parents to inform health-care provid-
tious diseases due to the loss of herd immu- ers that their child is not immunized during
nity, which puts many communities at risk acute illness (e.g., emergency room visit)
–– Vaccines are very safe, but they are not • Have parents sign vaccine refusal form in
risk-free, nor are they 100% effective every subsequent well visit
• Continued refusal after adequate discussion
Table 1.5 Immunization schedule summary should be respected unless the child is put at
Immunization significant risk of serious harm, e.g., refuses
schedule Vaccine rabies vaccines after the child was bitten by a
Birth HepB stray dog
2 months DTap, IPV, HepB, Hib, PCV, RV • In general, the pediatrician should not refuse
4 months DTap, IPV, HIB, PCV, RV
6 months DTap, IPV, HepB, Hiba, PCV, RVb,
a child care because caregivers reject vac-
Influenzac cines unless a strong sense of distrust devel-
12 months MMR, Varicella, Hib, PCV, HepA ops that impacts the child’s overall care
15–18 months DTap
18 months HepA (1st and 2nd dose must be 6 Recommended immunization schedule for chil-
months apart) dren and adolescents ages 18 years or younger,
4–6 years MMR, Varicella, DTap, IPV
11–12 years Tdap, MCV4 United States, 2018 (US Department of Health and
HPV (2-dose series 6–12 months Human Services, Centers for Disease Control and
apart)d Prevention) https://www.cdc.gov/vaccines/sched-
16 years Second dose of MCV4 ules/hcp/imz/child-adolescent.html
High risk PPSV23 2–18 years
MCV4 2–10 years
Meningococcal B (10 years and older)
DTaP Diphtheria and tetanus toxoids and acellular pertussis
Hepatitis B Vaccine (HepB)
vaccine, DTP Diphtheria, pertussis, and tetanus, HepA Hepatitis
A, HepB Hepatitis B, Hib Haemophilus influenzae type b (Hib) First dose of HepB is at birth
conjugate, HPV Human papillomavirus vaccine, IPV • Birth dose (monovalent HepB vaccine only)
Inactivated poliovirus vaccine, MCV4 Meningococcal conju-
gate ACWY vaccine, MMR Measles, mumps, and rubella, PCV Doses following birth dose
Pneumococcal conjugate vaccine, PPSV23 Pneumococcal • Administer the second dose 1–2 months after
polysaccharide vaccine, Tdap Tetanus and diphtheria toxoids
the first dose (minimum interval of 4 weeks)
and acellular pertussis vaccine, RV Rotavirus vaccine
a
Hib dose at 6 months is not required if using PedvaxHIB • Administration of four doses of HepB is per-
(Merck) missible if the combination is used after birth
b
Dose at 6 months is not required if using Rotarix (GSK) dose
c
Influenza every year beginning at 6 months
d
3 doses of HPV for persons initiating vaccination at age 15
years or older
16 O. I. Naga
• The final third or fourth dose in the HepB • If RotaTeq (RV5; Merck & Co.) is used,
series should not be administered before administer a 3-dose series at age 2, 4, and
6 months of age 6 months
• If any dose in the series was RotaTeq or vac-
Mother is HBsAg-negative cine product is unknown for any dose in the
• One dose within 24 h of birth for medically series, a total of 3 doses of RV vaccine should
stable infants ≥ 2000 g. For infants < 2000 g, be administered
administer one dose at chronological age
1 month or hospital discharge. Catch-up vaccination
• The maximum age for the first dose in the
Mother is HBsAg-positive series is 14 weeks, 6 days
• Give one dose HepB vaccine and 0.5 mL of • Vaccination should not be initiated in infants
hepatitis B immune globulin (HBIG) (at sep- of age 15 weeks, 0 days, or older
arate anatomic sites) within 12 h of birth, • The maximum age for the final dose is
regardless of birth weight. 8 months, 0 days
• Test for HBsAg and anti-HBs at age
9–12 months. If HepB series is delayed, test
1–2 months after final dose. DTaP/Tdap
Mother’s HBsAg status is unknown: DTaP (diphtheria and tetanus toxoids and acel-
• Give HepB vaccine within 12 h of birth, lular pertussis vaccine)
regardless of birth weight.
• For infants < 2000 g, give 0.5 mL of HBIG Administration
in addition to HepB vaccine within 12 h of • Minimum age 6 weeks (exception, DTaP-IPV
birth [Kinrix, GSK; Quadracel, Sanofi Pasteur],
• Give 3 additional doses of vaccine (total of 4 4 years)
doses) beginning at age 1 month • Not given to children 7 years and older
• Determine mother’s HBsAg status as soon as • Five-dose series DTaP vaccine at ages 2, 4, 6,
possible. If mother is HBsAg-positive, give 15–18 months, and 4–6 years
0.5 mL of HBIG to infants ≥ 2000 g as soon • The fourth dose may be administered as early
as possible, but no later than 7 days of age. as 12 months, if at least 6 months have elapsed
since dose 3
Catch-up vaccination
• An unvaccinated person should complete a Catch-up vaccination
three-dose series • The fifth dose of DTaP vaccine is not neces-
sary if the fourth dose was administered at
age 4 years or older
otavirus Vaccine (Two Available
R
in the USA) Tdap (tetanus and diphtheria toxoids and acel-
lular pertussis vaccine)
Minimum age is 6 weeks
• If Rotarix (RV1; GlaxoSmithKline [GSK]) is • Similar to DTaP but contain a smaller amount
used, administer a two-dose series at 2 and of pertussis antigen
4 months of age • Minimum age: 10 years for both Boostrix
(GSK) and Adacel (Sanofi Pasteur)
Administration • Family history of an adverse event after DTaP

• Administer one dose of Tdap vaccine to all administration
adolescents aged 11–12 years • Stable neurologic conditions (e.g., cerebral
palsy, well-controlled seizures, or develop-
Catch-up vaccination mental delay)
• A child 7 years and older who is not fully
immunized with DTaP vaccine should receive Haemophilus influenzae Type B (Hib) Conjugate
Tdap vaccine as one dose in the catch-up
series; if additional doses needed, use tetanus Vaccine
and diphtheria vaccine, adult/adolescent for- • Hib vaccine prevents invasive bacterial infec-
mulation (Td). tions usually caused by H. influenzae type b
• For children between 7 and 10 years who
receive a dose of Tdap as part of the catch-up Routine vaccination of Hib
series, an adolescent Tdap vaccine dose at • Administer a 2- or 3-dose Hib vaccine pri-
age 11–12 years should not be administered. mary series and a booster dose (dose 3 or 4,
Td should be administered instead, 10 years depending on vaccine used in primary series)
after Tdap dose. at age 12–15 months to complete a full Hib
vaccine series
DTaP inadvertently given after 7th birthday
• Child age 7–10 years: DTaP may count as Special situations
part of catch-up series. Routine Tdap dose at • Do not immunize immunocompetent children
11–12 should be administered 5 years of age or older, even if they never had
• Adolescent age 11–18 years: Count dose of Hib vaccine
DTaP as the adolescent Tdap booster. • Give one dose of Hib to unimmunized chil-
dren 5 years of age or older with HIV, func-
Absolute contraindication tional/anatomical asplenia
• History of encephalopathy within 7 days of • Give one dose of Hib to unimmunized children
dosing who are going for elective splenectomy, pref-
erably at least 14 days before the procedure
Relative contraindication • Children who are going for hematopoietic
• History of fever > 40.5 °C (105 °F) within stem cell transplant will need 3-dose series
48 h after prior dose with doses 4 weeks apart, starting 6–12 months
• Seizure within 3 days after successful transplant (regardless of Hib
• A shock-like condition within 2 days vaccination history)
• Persistent crying for more than 3 h within
2 days
Pneumococcal Vaccines
Vaccination may be administered under these
conditions 13-Valent pneumococcal conjugate vaccine
• Fever of < 105 °F (< 40.5 °C), fussiness, or (PCV13)
mild drowsiness after a previous dose of
DTaP Routine vaccination
• Family history of seizures • Administer a 4-dose series of PCV13 vaccine
• Family history of sudden infant death at ages 2, 4, and 6 months, and at age
syndrome 12–15 months
18 O. I. Naga
• PCV13 is recommended for all children Catch-up vaccination

younger than 5 years • Minimum age is 6 weeks
• The minimum interval between dose 1 to
Catch-up vaccination with PCV13 dose 2 and dose 2 to dose 3 is 4 weeks, the
• Administer 1 dose of PCV13 to all healthy minimum interval between dose 3 to dose 4
children aged 24–59 months who are not is 6 months
completely vaccinated for their age • The minimum age for final dose is 4 years
23-Valent pneumococcal polysaccharide vac-

cine (PPSV23) ral Poliovirus Vaccine (OPV)
O
• Protects children older than 2 years of age
against invasive disease caused by the 23 cap- • Live oral vaccine
sular serotypes contained in the vaccine • No longer used in the USA
Special situations: high-risk conditions (Table 1.6) Contraindication

• When both PCV13 and PPSV23 are indi- • Children with immunodeficiency
cated, administer PCV13 first • Children who live with adult HIV-infected or
• PCV13 and PPSV23 should not be adminis- immunocompromised
tered during same visit
Methods of vaccine administration (Table 1.7) Table 1.7 Methods of vaccine administration

Method of vaccine
administration Vaccine
Inactivated Poliovirus Vaccine (IPV) Oral Rotavirus
Oral polio vaccine (not used in the
Routine vaccination USA)
• Administer a 4-dose series of IPV at ages 2, Subcutaneous MMR
Varicella
4, 6–18 months, and 4–6 years IPV
• The final dose in the series should be admin- Intramuscular All other vaccines, including IPV
istered on or after the fourth birthday and at MMR Measles, mumps, and rubella, IPV Inactivated poliovi-
least 6 months after the previous dose rus vaccine
Table 1.6 PCV13 and PPSV23 administration to children with an underlying medical condition
PPSV23 PPSV23
Group and risks PCV13 Dose#1 Dose #2
Healthy children < 5 years Routine None None
Immunocompetent children and teens with 1 dose 8 weeks Age 2 years and older: None
underlying medical conditions, e.g., chronic heart before PPSV23a Administer 1 dose at
disease, chronic lung disease, (including asthma least 8 weeks after any
treated with high-dose, oral corticosteroids), diabetes prior PCV13 dose
mellitus, cerebrospinal fluid leak; cochlear implant
Children and teens with immunocompromising 1 dose 8 weeks Age 2 years and older: 1 additional dose at
conditions, nephrotic syndrome, malignant before PPSV23a Administer 1 dose at least 5 years
neoplasms, functional or anatomic asplenia least 8 weeks after any following the first
prior PCV13 dose PPSV23
PCV13 13-Valent pneumococcal conjugate vaccine, PPSV23 23-Valent pneumococcal polysaccharide vaccine
a
Children 2–5 years with any incomplete series of PCV13; not having received all doses in either the recommended series or
an age-appropriate catch-up series will need one PCV13 booster dose (if received 3 PCV13 doses series), and two PCV13
booster doses 8 weeks apart (if received < 3 PCV13 doses series), at least 8 weeks after any prior PCV13 dose
Influenza Vaccines –– Close contacts and caregivers of severely

immunosuppressed persons who require a
Minimum age protected environment
• 6 months: inactivated influenza vaccine (IIV) –– Pregnancy
• 2 years: live attenuated influenza vaccine –– Persons who have received influenza anti-
(LAIV) viral medications within the previous 48
• 18 years: recombinant influenza vaccine hours.
(RIV)
Routine vaccination
Measles, Mumps, and Rubella (MMR)
• 1 dose any influenza vaccine appropriate for Vaccine
age and health status annually (2 doses sepa-
Background
rated by at least 4 weeks for children
• MMR is a combination of 3 attenuated live
6 months–8 years who did not receive at least
viruses
2 doses of influenza vaccine before July 1,
• Not contraindicated in children with egg
2018)
allergy
Special situations
Routine vaccination
• Egg allergy, hives only
• Administer a 2-dose series of MMR vaccine
–– Give any influenza vaccine appropriate for
at ages 12–15 months and 4–6 years
age and health status annually
• Egg allergy more severe than hives (e.g., International travel to high-risk countries
angioedema, respiratory distress) • Age 6–11 months
–– Give any influenza vaccine appropriate for –– Administer 1 dose of MMR vaccine before
age and health status annually in medical departure from the USA
setting under supervision of health-care –– If the child remains in the high-risk area,
provider who can recognize and manage the second dose should be given at least
severe allergic conditions 4 weeks later
• LAIV should NOT be used in the following –– The dose before age of 12 months does not
conditions count towards the routine MMR vaccine
–– History of severe allergic reaction to any series
component of the vaccine (excluding egg) • Age 12 months and older
or to a previous dose of any influenza –– Administer 2 doses of MMR vaccine
vaccine 4 weeks apart before departure from the
–– Children and adolescents receiving con- USA
comitant aspirin or salicylate-containing
medications Catch-up vaccination
–– Children age 2–4 years with a history of • Ensure that all school-aged children and ado-
asthma or wheezing, those who are immu- lescents have had 2 doses of MMR vaccine;
nocompromised due to any cause (includ- the minimum interval between the 2 doses is
ing immunosuppression caused by 4 weeks
medications and HIV infection) • May not be given within 4 weeks of other live
–– Anatomic and functional asplenia, cochlear vaccines, but it can be given together or in
implants, cerebrospinal fluid-oropharyn- combination with varicella vaccine at the
geal communication same time
20 O. I. Naga
Contraindication Contraindication
• Anaphylactic reaction to neomycin or gelatin • Immunocompromised children
• Pregnancy; however, it is not an indication for • Pregnant women
abortion
• Immunodeficiency, e.g., AIDS; however, Vaccination may be administered under these
HIV-infected children can receive MMR live conditions
vaccine if not immunodeficient • Pregnancy of a recipient’s mother or other
close or household contact
Vaccination may be administered under these • Immunodeficient family member or house-
conditions hold contact
• Positive tuberculin skin test • Asymptomatic or mildly symptomatic HIV
• Simultaneous tuberculin skin testing infection
• Breastfeeding • Humoral immunodeficiency (e.g.,
• Pregnancy of recipient’s mother or other close agammaglobulinemia)
or household contact • Children with HIV or who live with an
• A recipient is female of childbearing age immunocompromised adult can take the
• Immunodeficient family member or house- vaccine
hold contact • The vaccine can be given to children who live
• Asymptomatic or mildly symptomatic HIV with a pregnant woman.
infection
• Allergy to eggs
aricella Zoster Immune Globulin
V
(VariZIG)
Varicella (VAR)
• Post-exposure to measles and varicella pro-
Background phylaxis (Table 1.8)
• Live attenuated virus vaccine contains a small
amount of neomycin and gelatin
• Two doses are recommended epatitis A (HepA) Vaccine
H
• Minimum age is 12 months, second dose at
4–6 years Routine vaccination
• The combination with MMR vaccine is now • Initiate the 2-dose HepA vaccine series
available (MMRV) at 12–23 months; separate the 2 doses by
6–18 months
Routine vaccination • Minimum age: 12 months for routine
• Administer a 2-dose series of VAR vaccine at vaccination
ages 12–15 months and 4–6 years
• The second dose may be given as early as Catch-up vaccination
3 months after the first dose (a dose given • Anyone 2 years of age or older may receive
after a 4-week interval may be counted) HepA vaccine if desired. Minimum interval
between doses is 6 months.
Catch-up vaccination
• Ages 7–12 years: Routine interval 3 months International traveling to countries with high or
(minimum interval, 4 weeks) intermediate endemic hepatitis A
• Ages 13 years and older: Minimum interval • Infants age 6–11 months: 1 dose before depar-
4 weeks ture; revaccinate with 2 doses, separated by
Table 1.8 Post-exposure to measles and varicella prophylaxis

Exposure of individuals
who have no evidence
of immunity Vaccine Immunoglobulin
Measles MMR vaccine within 72 hours of exposure Immunoglobulin can be given within 6 days
MMR vaccine should be offered at any interval of exposure to people at risk of severe
after exposure, as it may provide some protection illness or infants younger than 12 months;
MMR vaccination of infants 6–11 months if 6–11 months old, MMR vaccine can be
many measles cases appeared in infants < 12 given within 72 hours instead of
months immunoglobulin
Varicella To healthy individuals with no history of VariZIG within 10 days to the newborn
immunization who are 12 months or older within infant whose mother had chickenpox (not
3–5 days after varicella or herpes zoster exposure zoster) within 5 days before delivery or
within 48 hours after delivery
To immunocompromised children
MMR Measles, mumps, and rubella, VariZIG Varicella zoster immune globulin
6–18 months, between 12 and 23 months of Catch-up vaccination

age • Age 13–15 years: 1 dose now and booster at
• Unvaccinated age 12 months and older: first age 16–18 years (minimum interval, 8 weeks)
dose as soon as travel considered • Age 16–18 years: 1 dose
Post-exposure prophylaxis Special situations

• < 12 months: administer a single dose of Ig as • Anatomic or functional asplenia (including
soon as possible sickle cell disease), HIV infection, persistent
• ≥ 12 months: administer a dose of single- complement component deficiency, eculi-
antigen vaccine or Ig as soon as possible (the zumab use
efficacy of Ig or vaccine when administered
> 2 weeks after exposure has not been Menveo
established) • Dose 1 at age 8 weeks: 4-dose series at 2, 4,
6, 12 months
• Dose 1 at age 7–23 months: 2-dose series
Meningococcal Conjugate Vaccines (dose 2 at least 12 weeks after dose 1 and
after the 1st birthday)
Background • Dose 1 at age 24 months or older: 2-dose
• MCV4 or meningococcal conjugate vaccines series at least 8 weeks apart
(Men ACWY: Menactra, Sanofi Pasteur;
Menveo, GSK), reduce morbidity and mortal- Menactra
ity from meningococcal disease caused by • Persistent complement component deficiency:
serotypes A, C, W, or Y (does not cover for B –– Age 9–23 months: 2 doses at least 12 weeks
serotype) apart
–– Age 24 months or older: 2 doses at least
Routine vaccination 8 weeks apart
• Administer a single dose of Menactra or • Anatomic or functional asplenia, sickle cell
Menveo vaccine at age 11–12 years, with a disease, or HIV infection
booster dose at age 16 years –– Age 9–23 months: Not recommended
22 O. I. Naga
–– 24 months or older: 2 doses at least 8 weeks • Trumenba: 3-dose series at 0, 1–2, and 6 months
apart • Bexsero and Trumenba are not interchangeable
–– Menactra must be administered at least
4 weeks after completion of PCV13 series.
uman Papillomavirus (HPV)
H
Travel in countries with hyperendemic or epidemic Vaccines
meningococcal disease, including countries in the
African meningitis belt or during the Hajj Background
• Children age less than 24 months: • Prevent cervical cancer, precancerous genital
–– Menveo (age 2–23 months): lesions, and genital warts due to HPV type 6,
◦◦ Dose 1 at 8 weeks: 4-dose series at 2, 4, 11, 16, and 18
6, 12 months • 4vHPV (Gardasil, Merck & Co.) and 9vHPV
◦◦ Dose 1 at 7–23 months: 2-dose series (Gardasil 9)
(dose 2 at least 12 weeks after dose 1
and after the 1st birthday) Routine vaccination
–– Menactra (age 9–23 months): • Administer a 2-dose series of HPV vaccine
◦◦ Two-dose series (dose 2 at least 12 weeks on a schedule of 0 and 6–12 months to all
after dose 1; dose 2 may be administered adolescents aged 11 or 12 years
as early as 8 weeks after dose 1 in • The vaccination series can start at age
travelers) 9 years
• Children age 2 years or older: 1 dose of
Menveo or Menactra Catch-up vaccination
• For persons initiating vaccination at age
First-year college students who live in residential 15 years or older, the recommended immuni-
housing (if not previously vaccinated at age 16 zation schedule is 3 doses of HPV vaccine at
years or older) or military recruits: 1 dose of 0, 1–2, and 6 months
Menveo or Menactra
Special situations
Serogroup B meningococcal vaccines • History of sexual abuse or assault: Begin
• MenB vaccine may be administered based on series at age 9 years
individual clinical decision to adolescents not • Immunocompromised (including HIV) aged
at increased risk age 16–23 years (preferred 9–26 years: 3-dose series at 0, 1–2, and
age 16–18 years): (Bexsero, GSK; Trumenba, 6 months
Pfizer)
• Children 10 years or older who are at Vaccine content that may cause an allergic reac-
increased risk for serogroup B meningococ- tion (Table 1.9)
cal infections should be vaccinated, e.g.:
–– Asplenia (functional or anatomic)
–– Persistent complement deficiency
Common Adverse Reaction
–– Eculizumab use of Vaccines
Administration • Low-grade fever

• Bexsero: 2-dose series at least 1 month apart • Local reaction and tenderness
Table 1.9 Vaccine content that may cause an allergic • Fever of < 105 °F (< 40.5 °C); fussiness or
reaction mild drowsiness after a previous dose of DTP/
Contents in the vaccine DTaP
that may cause allergies Type of vaccine • Current antimicrobial therapy
Egg Influenza, yellow fever
• A family history of seizures, autism, or devel-
Egg allergy is no longer a
contraindication to influenza opmental delay
vaccine • Preterm birth (HepB vaccine is an exception
“In severe egg allergies (e.g., in certain circumstances)
angioedema, respiratory • Recent exposure to an infectious disease
distress) influenza vaccine can
be given under supervision of
• History of penicillin allergy, other non-vac-
health care provider who can cine allergies, relatives with allergies, or
recognize and manage severe receiving allergen extract immunotherapy
allergic conditions” • Positive purified protein derivative (PPD) test
Gelatin, neomycin MMR and varicella
Streptomycin, neomycin IPV and OPV Special considerations
MMR Measles, mumps, and rubella, IPV Inactivated poliovi- • If PPD not given with MMR on the same
rus vaccine, OPV Oral poliovirus vaccine
day, PPD test should wait for 4–6 weeks
(MMR may alter result if not done on the
Table 1.10 Contraindications to vaccinations
same day)
Vaccine Contraindications
Any vaccine Life-threatening allergic reaction after a
• If the infant vomited the rotavirus vaccine,
previous dose there is no need to re-administer the dose
Live vaccines, Known severe immunodeficiency again; complete the series normally
e.g., MMR, • Family history of intussusception or anaphy-
varicella, laxis is not a contraindication to give rotavi-
rotavirus
Rotavirus Personal history of intussusception (not rus vaccine
family history)
DTP, DTaP, or Encephalopathy not attributable to
Tdap another identifiable cause, within 7
days of administration of the previous PREVENTIVE MEDICINE [8]
dose
MMR Measles, mumps, and rubella, DTP Diphtheria, pertus- Newborn Screening
sis, and tetanus, DTaP Diphtheria and tetanus toxoids and
acellular pertussis vaccine, Tdap Tetanus and diphtheria tox-
oids and acellular pertussis vaccine
• All 50 states in the USA screen for:
–– Congenital hypothyroidism
Contraindications to Vaccinations –– Phenylketonuria
• Some states screen for more diseases, e.g.,
(Table 1.10)
metabolic and hemoglobinopathies
General conditions commonly misperceived as
History (initial/interval), length/height, and weight
contraindications (i.e., vaccination may be
• From birth and at all child well visits
administered under these conditions)
Head circumference measurements
• Mild acute illness with or without fever
• From birth and at all child well visits until
• Mild-to-moderate local reaction (i.e., swell-
24 months of age or at any time if any con-
ing, redness, soreness); low-grade or moder-
cern about the head growth
ate fever after the previous dose
24 O. I. Naga
Newborn Bilirubin Screening Vision Screening

• Screening for hyperbilirubinemia is recom- • Examination of eyes and visual system should
mended for all term and late preterm infants begin in the nursery and continue throughout
• Assessment of jaundice, risk factors for childhood and into adolescence
severe hyperbilirubinemia • Newborn infants should be examined using
• Measure total serum bilirubin or transcutane- inspection and red reflex testing to detect
ous bilirubin before discharging any newborn structural ocular abnormalities such as cata-
from the newborn nursery ract, corneal opacity, and ptosis before dis-
charge from the newborn nursery
• Instrument-based screening should be
Blood Pressure Screening attempted between 12 months and 3 years of
age and at annual well child visits until visual
• All children on yearly basis starting at 3 years acuity can be tested directly
of age • Visual acuity testing is now recommended for
• Blood pressure measurements at visits before children beginning at 3 years of age (if coop-
3 years if coexisting medical conditions asso- erative), 4, 5, 6, 8, 10, 12, and 15 years
ciated with hypertension
Screening tools
Pediatric cuff size (Fig. 1.11) • Ophthalmoscope
• Minimum bladder width • Photo-screening device
–– Bladder width should be at least 40% of • Lea symbols, Allen figures, HOTV letters,
mid arm circumference (MAC) Tumbling E, Snellen chart
• Bladder length
–– Bladder length should encircle 80–100% Cover and uncover test
of MAC, but no more than 100% • The child should be looking at an object from
a distance of 10 ft
Normal blood pressure (BP) • Movement in the uncovered eye when the
• < 90th percentile for age and sex opposite is covered or uncovered suggests
• Children whose BP is > 90th percentile for potential strabismus
age, sex, and height require further evaluation
Fig. 1.11 Pediatric cuff

size and accurate blood
pressure measurement:
Bladder width ≥ 40% of MAC
Relative sizes of patient’s
mid arm circumference,
cuff bladder width and
Bladder
length
Bladder length
encircling 80–100% of
mid arm circumference (MAC)
Hearing Screening • Screening tool at 18 and 24 months (See also

Chap. 6 Mental and Behavioral Health.)
Periodicity –– M-CHAT: Modified Checklist for Autism
• All newborns must receive newborn hearing in Toddlers (https://www.autismspeaks.
screening before discharge from the newborn org/screen-your-child; Autism Speaks)
nursery or NICU
• At age of 3–5 days, confirm initial screen was
completed, verify results, and follow-up as L ead Screening [9, 10]
appropriate
• Formal hearing screening is recommended at Ages of screening
age 4, 5, 6, 8, 10, and once between 11–14, • All Medicaid-eligible children and those whose
15–17, 18–21 years families receive any governmental assistance
must be screened at age 1 and 2 years
Goal of screening
• Identify hearing loss of 35 dB or greater in Elevated blood lead level (BLL)
500–4000 Hz range • There is no safe BLL
• Lead poisoning is diagnosed if the BLL is
Indication for hearing screening in special ≥ 5 mcg/dL (0.24 mmol/L)
situations • BLL for children 1–5 years old should be less
• Speech delay than 2 mcg/dL
• Parental expression of concern on hearing • An elevated capillary BLL should be con-
problem, language, or developmental delay firmed with a venous sample
• History of bacterial meningitis
• Neonatal CMV infection Risk factors for lead poisoning
• Head trauma • Living in or regularly visiting a house built
• Syndromes associated with hearing loss, e.g., before 1950 or remodeled before 1978
Alport syndrome • Other sibling or family member with a high
• Exposure to ototoxic medications lead level
• Immigrant or adopted children
• Use of folk remedies
Developmental Screening • Environment with high or unknown lead level
• Children eligible for Medicaid are at high
• Developmental screening at 9, 18, and risk
30 months of age
Effect of lead intoxication
• A decline in academic achievement, intelli-
Autism screening gence quotient (IQ) scores, attention-related
behaviors with BLL < 10 mcg/dL
• AAP Bright Futures recommends autism • Microcytic anemia
screening at 18 and 24 months of age –– Concomitant iron deficiency anemia;
• Repeat specific screening whenever parental increased lead absorption
concern raised • Abdominal colic
• Positive screening: If < 3 years of age, refer to • Constipation
early intervention (EI); if > 3 years of age, • Growth failure
refer to the school district for further • Dental caries
evaluation • Hearing loss
26 O. I. Naga
• Renal disease Urinalysis (UA) Screening

• Neurotoxicity
• Seizures • No routine screening recommended by AAP
• Encephalopathy Bright Futures at this time
• Death
Management of lead poisoning, any detectable Sexually Transmitted Diseases

or elevated BLL (Table 1.11)
• Recommendations for screening sexually
active adolescents for sexually transmitted
Iron Deficiency Anemia Screening infections vary with age, sex, and sexual
• AAP Bright Future recommends universal behavior.
anemia screening with determination of
hemoglobin concentration at 1 year of age
HIV Screening
Screening of high-risk children
• The US Preventive Services Task Force rec-
• Prematurity
ommends that clinicians screen for HIV
• Low birth weight
infection in all adolescents once between 15
• Early introduction of cow’s milk
and 18 years of age
• Strict vegans
–– Younger adolescents who are at increased
• Poverty
risk should also be screened
• Limited access to food
–– Risk factors, e.g., male-to-male sexual con-
• Associated medical conditions
tact, injection drug use, heterosexual contact
Table 1.11 Management of lead poisoning, any detectable or elevated blood lead level (BLL)
BLL Management Re-testing venous BLL
Any detectable or elevated Education Periodic follow-up
BLL Environmental investigations
BLL > 5 mcg/dL Education In 6–12 months if the child
Environmental investigations is at high risk
In 3–6 months if < 12
months old
BLL 5–14 mcg/dL Refer to local health authorities Re-test venous BLL within
CBC, CRP, and serum ferritin 1–3 months
Iron-rich food and vitamin C
BLL 15-44 mcg/dL In addition to previous steps of BLL 5–14 mcg/dL, if pica Re-test venous BLL within
for paint chips or mouthing behaviors, perform KUB; bowel 1–4 weeks
decontamination if foreign bodies containing lead are
visualized
BLL > 44 mcg/dL Perform chelation therapy Re-test venous BLL within
48 h if no symptoms
BLL > 69 mcg/dL Hospitalization and chelation therapy Re-test venous BLL within
24 h if no symptoms
Symptomatic lead Hospitalize for full investigations, decontamination, and Medical emergency
intoxication chelation therapy. PICU admission if lead encephalopathy Confirm with a stat BLL
CBC Complete blood count, CRP C-reactive protein, KUB Kidneys, ureters, and urinary bladder, abdominal radiograph,
PICU pediatric ICU
Screening test for HIV ral Health Screening

O
• Rapid HIV testing or HIV immunoassay
• The reactive test followed by confirma- • Perform dental risk assessment at 6 and
tory Western blot or immunofluorescent 9 months of age
assay • The AAP recommends repeat oral health
assessment at 12, 18, 24, and 30 months and
3, 4, 5, and 6 years of age if the child has not
Tobacco, Alcohol, And Substance Use yet established a dental home
• The AAP recommends the initial dental visit
• Annual screening for tobacco, alcohol, and at 12 months of age
substance use, beginning at age 11 years
Fluoride supplementation
epression Screening
D • Periodic application of fluoride varnish
between 6 months and 5 years of age
• Universal screening for depression annually • No fluoride should be given to an infant of
from age 12 to 21 years less than 6 months
• Screening for depression in children • If the fluoride in the water supply < 0.3 PPM
≥ 10 years and adolescents at high risk of begin supplementation at 6 months of age
depression • If fluoride in the water supply is > 0.6 PPM,
no need for taking extra fluoride
Tooth care
Tuberculosis (TB) Screening • Once tooth erupts, it should be brushed twice
daily with plain water
• The AAP/Bright Futures guidelines suggest
• Once the child reaches 2 years of age, brush
tuberculosis risk assessment by 1 month of
teeth twice daily with a pea-sized amount of
age; at ages 6, 12, and 24 months; and annu-
fluoride toothpaste
ally thereafter
• Daily flossing
Prevention of bacterial transmission ( Streptococcus

Dyslipidemia
mutans or S. sobrinus)
• Routine screening for dyslipidemia in all • Practice good oral hygiene and seek dental care
children once between 9 and 11 years and • Do not share utensils, cups, spoons, or tooth-
once between 17 and 21 years brushes with an infant
• Do not clean a pacifier by mouth before giv-
Screening methods ing it to an infant
• Non-fasting non-HDL-cholesterol
• Screen for dyslipidemia in a child between 2 Risk group infants should be referred to a dentist
and 8 years of age if parent has a total choles- as early as 6 months of age and no later than
terol of 240 mg/dL or higher: A fasting lipid 6 months after the first tooth erupts or 12 months of
profile should be obtained and then repeated age (whichever comes first) for the establishment
after 2 weeks to 3 months (See also Chap. 19 of a dental home. Examples of risk group infants:
Cardiology.)
• Children with special health-care needs
• Children of mothers with a high caries rate
28 O. I. Naga
• Children with demonstrable caries, plaque, Table 1.12 Routine screening in pediatrics
demineralization, and/or staining Ages to be Special
• Children who sleep with a bottle or are breast- Screening performed considerations
feed throughout the night Length/height From birth and in Repeat and confirm
and weight each well visit any abnormal
• Children in families of low socioeconomic reading
status Head From birth until the Repeat and confirm
circumference age of 2 years any abnormal
Summary of Routine screening in Pediatrics reading or any time
(Table 1.12) if any concern about
head size
Blood pressure 3 years of age, then Before 3 years of
yearly after age visits if any risk
WELL CHILD VISITS factor of
hypertension
Well Visit Schedule Hearing Newborn, 4, 5, 6, 8, Any time if any risk
10, and once at factor
Infancy 11–14, 15–17,
18–21 year
• Newborn Vision 3, 4, 5, 6, 8, 10, 12, Any time if any
• 3–5 days old 15 year concern
• 1, 2, 4, 6, and 9 months Developmental 9, 18, and 30 Any time if any
screening months concern
Early childhood Autism 18 and 24 months Any time if any
screening concern
• 12, 15, 18, 24, 30 months; 3 and 4 years
Depression 12 years of age, Any time if any
then yearly after signs of depression
Middle childhood Maternal 1, 2, 4, and Any time if any
• Yearly from 5 to 10 years depression 6-month visits signs of depression
Bilirubin Newborn Any time if
Adolescents indicated
• Yearly from 11 to 21 years Anemia 12 months Any time if
indicated
Lead 12 and 24 months if Any time if any risk
Counseling during each well visit is very Medicaid or high factor
important risk of prevalence
• Bath safety area
• Sun exposure Tuberculosis Risk assessment at Any time if any risk
• Fluoride supplementation 1, 6, 12, and 24 factor
months, and
• Nutrition annually thereafter
• Immunization Dyslipidemia 9–11, and once at Any time if
• Common cold management 17–21 years indicated
HIV Once between 15 Younger if
Age-appropriate anticipatory guidance, e.g.: and18 years increased risk of
• Feeding the newborn HIV infection
Oral health Perform dental risk Refer to establish a
• Dental care when the first tooth appears assessment at 6 and dental home at 12
• Dental appointment at 12 months if pediatric 9 months, fluoride months of age
dentist is available varnish every 3-6
• Limitations on screen time (TV, computer, months between 6
months and 5 years
phone)
of age
• Encourage reading to the child, and by the Anticipatory From birth and in Any time if parents
child guidance each well visit have a concern
• Helmet for bicycle • Children no longer need to use a booster seat

• Discussion about tobacco, alcohol, drug use, if the seat belts fit properly when the lap belt
and sex at age of 11 and up lays across the upper thighs (not the stomach)
and the shoulder belt lays across the chest
(not the neck)
ENVIRONMENTAL SAFETY
COUNSELING Car seat or bed screen before discharging a
pre-term baby from NICU [12]
Preventing Motor Vehicle Injuries in • Indications for screening
–– Infants < 37 weeks gestation
Children [11] –– At risk for obstructive apnea, bradycardia,
Children should be properly buckled up in a car or hypoxemia, including infants with hypo-
seat, booster seat, or seat belt, whichever is appro- tonia (e.g., Down syndrome), micrognathia
priate for their age, height, and weight (e.g., Pierre Robin sequence)
• All children aged 12 years and under should –– After cardiac surgery
be buckled in the back seat • Infants “fail” the screen if they have
• Airbags can kill young children riding in the –– Oxygen desaturation below 90% or 93%
front seat for more than 10 s
• Never place a rear-facing car seat in front of –– Apnea greater than or equal to 20 s
an airbag –– Bradycardia less than or equal to 80 beats
per minute
Rear-facing car seat
• Birth until 2–4 years of age
• Buckle children in a rear-facing car seat until Preventing Drowning
they reach the maximum weight or height
• Enclose pools entirely with fence and least
limit of their car seat
4 ft high and self-closing gate
• Keep children rear-facing as long as
• Wear life jackets on boats and when playing
possible
near water
Forward-facing car seat • Do not leave children unattended in baths
• After out-growing rear-facing car seat until at • Supervise closely (adults within one arm’s
least 5 years of age reach of a child in or near water)
Booster seat
• After outgrowing the forward-facing car seat P reventing Fire and Burns
until seat belts fit properly
• The recommended height for proper seat belt • Install a smoke detector on every level of the
fit is 57 in. (4 ft 9 in.) tall and 9–12 years of home and near sleeping areas
age • Reduce water heater temperature to 120 °F
• Do not drink hot fluids near children
Seat belt • Never leave the stove unattended
• Once seat belts fit properly without a booster
seat
30 O. I. Naga
Preventing Gun Accidents Preventing Bicycle Injuries [14]

• If parents choose to keep a firearm in the • Children between the ages of 5 and 14 years
home, the unloaded gun and ammunition are at the highest risk for bicycle injury
must be kept in separate locked cabinets • Head injuries account for the majority of
bicycle-related deaths and hospital
admissions
Preventing Poisoning • Children < 1 year should not ride in bicycle-
mounted carriers or trailers
• Keep all potential poisons in original contain- • Children < 3 years do not have the develop-
ers and out of reach mental skills necessary to ride a tricycle
• Keep all medications out of reach • Children aged 4–5 usually can ride a bicycle
• Place child-resistant caps on medications with training wheels and foot-operated
• Install carbon monoxide detectors on every brakes; they should not ride in traffic and
level of the home must always be supervised
• Keep the 24-h Poison Control number near • Children 6 years or older usually can ride a
the phone: 1-800-222-1222 (National Capital bicycle without training wheels and operate
Poison Center). hand brakes
• Online: webPoison Control. https://triage. • Children should not be permitted to ride in
webpoisoncontrol.org/#/exclusions traffic until they have demonstrated that they
can control the bicycle, understand and fol-
low the rules of the road, and exercise good
Preventing Threats to Breathing [13] judgment
• Reflectors are important to increase visibility
• Remove comforters, pillows, bumpers, and
in the dark; however, bicycling in the dark
stuffed animals from crib
should be discouraged
• The AAP recommends:
• Use bicycle lanes and bicycle paths
–– Hard candy and gum not be given to chil-
• Keep children < 10 years off the road
dren younger than age 5 years
–– Raw vegetables and fruit be cut up into
small pieces Bicycle helmets
–– Children should always be supervised while • Reduce the risk of head, brain, and severe
eating and that children be seated when eat- brain injuries for bicyclists of all ages
ing—not running, walking, or lying down • Should be encouraged for riders and passen-
–– Caregivers should be familiar with chok- gers of all ages, on every occasion that they
ing-related rescue maneuvers ride a bicycle
• Should fit properly and be worn in the proper
position
Preventing Falls • Only those that meet US Consumer Product
Safety Commission standards should be used
• No baby walkers with wheels
• Helmets that have been involved in a crash
• Baby walkers increase risk of falls and skull
should be discarded
fracture
• Helmets should be replaced every 5 years
Preventing Sunburn [15] Preventing Mosquito Bites [16]

• Sunburn increases risk of melanoma at all Example of effective repellents
ages • DEET (N,N-diethyl-3-methylbenzamide)
repels mosquitoes, ticks and other bugs; used
Sun avoidance on the skin only
• Wear protective clothing • Permethrin products (repel mosquitoes and
• Seek shade or reduce exposure to the sun ticks and can be used on clothing)
between 10:00 AM–2:00 PM, when sunlight • Picaridin (can be used on the skin or clothing)
intensity is greatest, especially in the
summer DEET
• Protective clothing such as long sleeves and • Repellents with 10–30% DEET should be
wide-brim hats should be worn while safe and effective when used according to the
outdoors directions on the product labels
• Repellents with 10% DEET concentration are
Sunscreens effective for periods of approximately 2 h
• Broad spectrum sunscreens with a sun pro- • Repellents with 24% DEET concentration are
tection factor (SPF) of at least 30 or higher on effective for periods of approximately 4 h
both cloudy and sunny days • Higher concentrations provide longer dura-
• Sunscreen rated SPF 30 filters 97% of UVB tions of protection
rays while SPF 50 blocks 98%. • Protection is shortened by swimming, wash-
• Sunscreens should be applied 15–30 min ing, rainfall, sweating, and wiping
before sun exposure to allow the formation of
a protective film on the skin Recommended age for repellents
• Reapply sunscreen every 2 h and after swim- • Children 2 months or older
ming or sweating • Children younger than 2 months of age should
not use products with DEET
Infants younger than 6 months
• For infants younger than 6 months, the Adverse effects
AAP recommends avoidance of sun expo- • Dermatitis, allergic reactions, and rare neuro-
sure and the use of clothing (e.g., light- toxicity from excessive absorption through
weight pants, long-sleeved shirts, brimmed the skin
hats) • Avoid using sunscreen products containing
• A minimal amount of sunscreen with an SPF DEET because of possibility of reapplication
of ≥ 15 may be applied to small areas (e.g., and excessive absorption of DEET
face, back of the hands) when adequate cloth- • Once the child is indoors, wash off the skin
ing and shade are not available with water to avoid excessive absorption
Complications of mosquito bites

rtificial Ultraviolet Rays (Tanning)
A • Urticarial reaction
• Large local reaction; itchy or even painful
• Artificial ultraviolet rays may cause sunburn, area of redness, warmth, swelling, and/or
skin dryness, pruritus, and photokeratitis induration that ranges from 2 cm to more than
• Long-term exposure may cause cataracts, 10 cm in diameter
skin aging, and cancer • Malaria and West Nile virus infections in
high-risk areas
32 O. I. Naga
• Bacterial cellulitis: Differential diagnosis

–– It is not common • Gastrointestinal causes (e.g., gastroesopha-
–– Malaise, chills, fever, and toxicity may be geal reflux disease [GERD], over- or under-
present feeding, milk protein allergy, early
–– The involved area is red, hot, swollen, and introduction of solids)
tender • Exposure to cigarette smoke and its metabolites
–– May take days to develop versus minutes • Food allergy
to hours in cases of local reaction
–– Without treatment, bacterial cellulitis will Management of infantile colic [17]
continue to get worse versus local reaction, • Parents need to be reassured that they have a
which will improve with time healthy infant
• Effective swaddling, and decreased stimula-
Prevention of large local reaction tion of the infant
• Mosquito avoidance • Hold and comfort, e.g., gentle rocking, danc-
• Prophylaxis with an oral non-sedating H1 ing with the baby, wind-up swing, or vibrat-
antihistamine ing chair
• Cautioning overtired and frustrated parents
Treatment of large local reactions never to shake their infant and giving them
• Antihistamines permission to allow the infant to cry are
• Ice in a wet washcloth for 20 min essential components of any treatment plan
• Topical hydrocortisone cream and can decrease the risk of child abuse
• Systemic glucocorticoids in severe cases • A breastfeeding mother should avoid caffeine
• Probiotics and/or simethicone may help (no
data to support the routine use of these
CRYING INFANT therapies)
Infantile Colic Dietary changes may include the following

• Elimination of cow’s milk protein in cases of
Background suspected intolerance of the protein
• Colic begins during the 2nd week of life, • In infants with suspected cow’s milk allergy,
peaks at 6 weeks, and resolves between 12 a protein hydrolysate formula is indicated
and 16 weeks • Soy-based formulas are not recommended,
• Equally common in both breast- and bottle- because many infants who are allergic to
fed infants cow’s milk protein may also become intoler-
• Average crying per day: 2.2 h ant of soy protein
• May cause parental anxiety and may increase
the risk of postpartum depression
Normal physical findings PEARLS AND PITFALLS

• Weight gain:
–– Infants with colic often have accelerated • Crossing percentiles in the growth curve for
growth; failure to thrive should make any child must be investigated initially by
one suspicious about the diagnosis of colic repeating the measurement to ensure
–– Exclusion of organic causes, e.g., infec- accuracy.
tion, occult fractures, or maternal drug • Rotavirus vaccine is contraindicated in infants
effects with personal history of intussusception or
• Should respond to comforting personal history of anaphylaxis to rotavirus
• Baby acts happy between bouts of crying vaccine.
• Family history of intussusception or anaphy- ineffective remedy for the treatment of infan-
laxis to rotavirus is not a contraindication to tile colic.
rotavirus vaccine. • There is no safe blood lead level (BLL). Any
• For any child with abnormal red reflex, or any detectable BLL must be managed and investi-
parental concern about white pupil reflex, the gated further.
most prudent action is to refer the patient for • Intake of milk above 16–24 oz is associated
a complete ocular examination. with increased risk of iron deficiency and
• Any new-onset strabismus is a red flag for subsequent anemia.
ocular or intracranial structural abnormalities • Growing pains is a diagnosis of exclusion,
e.g., brain tumor. requires that symptoms only occur at
• Screen all adolescents for HIV once between night, and that the patient has no limp, no
age 15 and 18 years. joint swelling, or symptoms during the
• To prevent drowning, children should be day.
supervised closely (adults within one arm’s
reach of a child in or near water).
• If parents choose to keep a firearm in the References
home, the unloaded gun and ammunition
must be kept in separate locked cabinets. 1. Braun LR, Marino R. Disorders of growth and
• Hard candy and gum should not be given to stature. Pediatr Rev. 2017;38(7):293–304.
children younger than age 5 years and raw 2. Nicol L, Allen DB, Czernichow P, Zeitler
vegetables and fruit should be cut into small P. Normal growth and growth disorders. In:
pieces. Kappy MS, Allen DB, Geffner ME, editors.
• Baby walkers with wheels increase risk of Pediatric practice endocrinology. New York:
falls and skull fracture. McGraw-Hill; 2010. p. 23–76.
• Bicycle helmets reduce the risk of severe 3. Losee JE, Mason AC. Deformational plagio-
head and brain injuries for bicyclists of all cephaly: diagnosis, prevention, and treatment.
ages. Clin Plast Surg. 2005;32(1):53–64, viii.
• Broad-spectrum sunscreens with SPF 30 or 4. Scharf RJ, Scharf GJ, Strousup
higher should be regularly used when per- A. Developmental milestones. Pediatr Rev.
forming outdoor activities in sunny weather, 2016;37(1):25–37; quiz 38, 47.
especially in regions with high levels of 5. Feigelman S. Growth, development, and behav-
insolation. ior. In: Kliegman RM, Stanton BF, Schor NF,
• Keep infants younger than 6 months away St. Geme III JW, Behrman RE, editors. Nelson
from the sun. textbook of pediatrics. 19th ed. Philadelphia:
• To prevent mosquito bites, repellents with Elsevier Saunders; 2011. p. 26–32.
10–30% DEET are recommended for chil- 6. U.S. Department of Health and Human
dren 2 months and older. Services Centers for Disease Control and
• Children younger than 2 months of age should Prevention. Recommended immunization
not use products with DEET. schedule for children and adolescents aged
• Infantile colic is a self-limited condition that 18 years or younger—United States 2019.
will spontaneously resolves between 12 and https://www.cdc.gov/vaccines/schedules/hcp/
16 weeks. imz/child-adolescent.html. Accessed 16 Feb
• Effective swaddling, gentle rocking, and 2019.8.
decreased stimulation of the infant are helpful 7. U.S. Department of Health and Human
measures in the management of infantile colic. Services. Centers for Disease Control and
• Simethicone, considered by many as a main- Prevention. Immunization schedules for health
stay of colic treatment, is a safe but relatively care professionals. 26 May 2016. https://www.
34 O. I. Naga
cdc.gov/vaccines/schedules/hcp/index.html. 13. Green SS. Ingested and aspirated foreign bod-

Accessed 29 Sep 2018. ies. Pediatr Rev. 2015;36(10):430–6.
8. Bright Futures/American Academy of Pediatrics. 14.
Gill AC. Bicycle injuries in children:
Recommendations for Preventive Pediatric Prevention. Post TW, editor. Waltham, MA:
Health Care (periodicity schedule). 2017. UpToDate Inc. http://www.uptodate.com.
https://www.aap.org/en-us/Documents/period- Accessed 14 Oct 2018.
icity_schedule.pdf. Accessed 23 Sep 2018. 15. Young AR, Tewari A. Sunburn. Post TW, edi-
9. Academy of Pediatrics. Committee on envi- tor. Waltham, MA: UpToDate Inc. http://www.
ronmental health. Lead exposure in children: uptodate.com. Accessed 14 Oct 2018.
prevention, detection, and management. 16. Breisch NL. Post TW, editor. Prevention of
Pediatrics. 2005;116(4):1036–46. arthropod and insect bites: repellents and other
10.
Lowry JA. Childhood lead poisoning: measures. Waltham: UpToDate Inc.. http://
Management. Post TW, editor. Waltham, MA: www.uptodate.com. (Accessed 14 Oct 2018
UpToDate Inc. http://www.uptodate.com. 17. Cohen GM, Albertini LW. Colic. Pediatr Rev.
Accessed 14 Oct 2018. 2012;33(7):332–3.
11.
U.S. Department of Health and Human
Services. Centers for Disease Control and
Prevention. Child passenger safety: get the Suggested Reading
facts. 11 2017. https://www.cdc.gov/motorve-
hiclesafety/child_passenger_safety/cps-fact- Kelly NR. Screening tests in children and adoles-
sheet.html. Accessed 29 Oct 2018. cents. Post TW, editor. Waltham, MA: UpToDate
12. Smith VC, Stewart J. Discharge planning for Inc. http://www.uptodate.com. Accessed on 14
high-risk newborns. Post TW, editor. Waltham, Oct 2018.
MA: UpToDate Inc. http://www.uptodate.com. Olney AH. Macrocephaly syndromes. Semin
Accessed 14 Oct 2018. Pediatr Neurol. 2007;14(3):128–35.
Neonatology
2
Mamta Fuloria
DEFINITIONS Very low birth weight (VLBW)

• BW < 1500 g
Live birth
• Live birth occurs when a fetus, whatever its Extreme low birth weight (ELBW)
gestational age, exits the maternal body and • BW of less than 1000 g (2 lb., 3 oz)
subsequently shows any signs of life, such as
Preterm
voluntary movement, heartbeat, or pulsation
• An infant born at < 37 weeks GA
of the umbilical cord, for however brief a
time and regardless of whether the umbilical Term
cord or placenta is intact • An infant born between the 37 0/7 and
41 6/7 weeks of gestation
Gestational age (GA)
–– Early term: Between 37 0/7 and 38 6/7 weeks
• The number of weeks in a pregnancy since
of gestation
the 1st day of the last menstrual period or the
–– Full term: Between 39 0/7 and 40 6/7 weeks
corresponding age of gestation as estimated
of gestation
by a more accurate method if available. Such
–– Late term: Between 41 0/7 and 41 6/7 weeks
methods include an early obstetric ultraso-
of gestation
nography or by adding 14 days to a known
duration since fertilization (in patients who Post-term
have undergone in vitro fertilization) • An infant born after 42 0/7 weeks of
gestation
Small for gestational age (SGA)
• Birth weight (BW) < 10th percentile for the
given GA
PRENATAL CARE
Large for gestational age (LGA)
• BW > 90th percentile for the given GA Routine Prenatal Laboratory Tests
Low birth weight (LBW) • Urine for protein, glucose, and bacteriuria
• BW < 2500 g regardless of the GA • Complete blood count (CBC)
• Blood type and Rh
M. Fuloria (*) • Red blood cell (RBC) antibodies
Division of Neonatology, Department of Pediatrics, The Children’s • Hepatitis B surface antigen
Hospital at Montefiore, Albert Einstein College of Medicine,
Bronx, NY, USA
• Rapid plasma reagin (RPR) or venereal dis-
e-mail: mfuloria@montefiore.org ease research laboratory test (VDRL)
36 M. Fuloria
Table 2.1 Significant fetal ultrasonographic anatomic find- • Multiple births

ings and postnatal management • Placental bleeding – placenta previa, placen-
Prenatal US tal abruption
finding Causes Postnatal evaluation • Uterine abnormalities
Dilated Hydrocephalus, Serial head US or
• Premature rupture of membranes
cerebral Dandy-Walker cyst, MRI, evaluation for
ventricles agenesis of corpus other system • Preterm delivery
callosum anomalies • Chorioamnionitis
Choroid Trisomy 18; can be Karyotype if • Maternal drug abuse, e.g., cocaine
plexus cyst a normal variant indicated, Head US or • Bacterial vaginosis
MRI scan, evaluation
for other system
anomalies
Known risk factors for prematurity
Nuchal pad Cystic hygroma, Evaluation for other • Placental bleeding
thickening Turner syndrome, system malformation, • Uterine abnormalities
trisomy 18 or 21 karyotype if indicated • Use of drugs such as cocaine
Dilated Ureteropelvic Renal ultrasound • Smoking
renal pelvis junction obstruction, between day 5 and 7
vesicoureteral and at 4–6 weeks of
• Alcohol intake
reflux, posterior age; voiding • Maternal chronic disease
urethral valve, cystourethrogram and • Premature rupture of membranes
ectopic ureterocele prophylactic antibiotic • Prior history of preterm delivery
if indicated • Chorioamnionitis
MRI magnetic resonance imaging, US ultrasonography
• Bacterial vaginosis
• Preeclampsia or hypertension
• Human immunodeficiency virus (HIV)
• Maternal age: < 18 years and > 35 years
screening
• Rubella antibodies Factors associated with high mortality rate in
• Blood work for neural tube defects and chro- preterm infants
mosomal abnormalities, if indicated • Younger GA
• Ultrasound at 18–20 weeks, if indicated • Male sex
(Table 2.1) • 5 min Apgar < 4
• Glucose challenge and/or glucose tolerance • Persistent bradycardia at 5 min
tests between 24 and 28 weeks gestation (for • Hypothermia
diagnosing gestational diabetes) • Intrauterine growth restriction
• Vaginal and rectal culture for group B strep-
tococcus (GBS) between 35 and 37 weeks
gestation, and intrapartum antibiotics if Umbilical Cord
indicated
• Education about nutrition, vitamins, and • Umbilical cord has two arteries and one vein
pregnancy course • Single artery umbilical cord can be associ-
• Prenatal care delayed until after the first tri- ated with other organ anomalies, e.g., heart
mester is associated with higher infant mor- and kidneys
tality rate • Umbilical cord length is about 55 cm; umbili-
cal cord < 40 cm is short and can be associ-
General neonatal risks ated with fetal complications, e.g., amniotic
• Delayed prenatal care band and arthrogryposis
• Maternal age: Teens and > 40 years of age • Longer cord more than 55 cm may be associ-
• Male infants have higher mortality rates than ated with knots, prolapse, or may entwine the
female infants fetus
2 Neonatology 37
Placenta • Variable deceleration is associated with

compression of the umbilical cord
• Placenta accreta: Develops when the chori- • Late deceleration is associated with utero-
onic villi attaches to the myometrium of the placental insufficiency. Thus, maternal
uterine wall rather than being restricted within hypotension, uterine hyperstimulation, pre-

the decidua basalis; may occur because of eclampsia, or any other factor that reduces
previous trauma, e.g., previous cesarean sec- uterine blood flow and limits effective oxy-
tion, and curettage genations of the fetus will result in late decel-
• Placenta increta: Develops when the chori- erations and decreased baseline variability.
onic villi invades into the myometrium –– Persistent late decelerations associated
• Placenta percreta: Develops when the chori- with decreased beat-to-beat variability is
onic villi invades through the myometrium, an ominous pattern
sometimes extending to nearby organs such as –– If late deceleration is not responding to
the bladder, resulting in serious bleeding oxygen supplementation, hydration, posi-
• Placental abruption: tion change, and discontinuation of labor
–– Develops when the placenta separates from stimulation, prompt delivery is indicated
the wall of the uterus, either partially or • Contraction stress test is performed to
completely, before birth of the infant determine how well a fetus will tolerate uter-
–– Hemorrhage into the decidua basalis occurs ine contractions during delivery. It is impor-
as the placenta separates from the uterus tant for testing the wellbeing of fetus, e.g., in
–– Vaginal bleeding usually follows, although uteroplacental insufficiency, IUGR
a concealed retroplacental hemorrhage is –– Contraction stress test measures the heart
possible rate in relation to uterine contraction by
giving oxytocin or nipple stimulation
• Biophysical profile test assesses fetal heart
C
esarean Section (C-section): rate, movement, breathing, muscle tone, and
Indications amniotic fluid volume. It does not assess fetal
growth
• Previous C-section
• Fetal distress Causes of abnormal alpha-fetoprotein (AFP)
• Dystocia during pregnancy
• Fetal malpresentation • Increased AFP
• Placenta previa –– Neural tube defect
• Placenta accreta, increta, and percreta • Anencephaly
• Other • Spina bifida
–– Abdominal wall defects
• Gastroschisis
Fetal Distress • Omphalocele
–– Cystic hygroma
Definitions –– Placental abnormalities
• Nonstress test is the most common nonin- –– Renal abnormalities, e.g.:
vasive test; it monitors fetal heart rate accel- • Polycystic kidney or absent kidney
erations that follow fetal movement over • Urinary obstruction
time –– Multiple pregnancy
• Early deceleration is associated with head • Decreased AFP
compression during uterine contraction, –– Incorrect GA calculation
resulting in vagal stimulation and slowing of –– Trisomy 21 (Down syndrome)
the heart rate –– Trisomy 18 (Edward syndrome)
38 M. Fuloria
DELIVERY ROOM CARE [1] –– Chest compressions are required if the

infant’s heart rate remains < 60 bpm despite
adequate ventilation for 30 s. Chest com-
Temperature control
pressions must always be accompanied by
• To minimize heat loss, the delivered infant is
PPV using 100% oxygen
first placed in a warmed towel or blanket
–– Pulse oximetry is used to continuously
• Raising the environmental (room) tempera-
monitor heart rate and oxygen saturation
ture to 26 °C (78.8 °F) will also help in reduc-
(SpO2)
ing neonatal hypothermia
–– Intubation or use of a laryngeal mask air-
• Other methods of warming infants:
way is needed if PPV is ineffective or pro-
–– Swaddle after drying
longed, or chest compressions are being
–– “Skin-to-skin” contact with mother
performed
–– Polyurethane bags or wraps in infants with
• If the heart rate remains < 60 bpm despite
BWs less than 1500 g
adequate ventilation and chest compressions:
–– Warming pads
–– Intravenous administration of epinephrine
Initial management—Once the infant is born: is indicated (epinephrine can also be given
• Dry the infant via the endotracheal tube if vascular access
• Clear the airway of secretions is not available)
• Provide warmth; place under radiant warmer –– Cannulation of the umbilical vein is the
• Neonatal resuscitation if indicated quickest means of obtaining intravenous
(IV) access in the newborn
Newborn resuscitation • For infants with labored breathing or persis-
• Pediatrician or provider skilled in neonatal tent cyanosis, and a heart rate ≥ 100 bpm:
resuscitation should be present and equip- –– Ensure the airway is optimally positioned
ment should be prepared prior to the birth of and cleared of secretions; pulse oximetry is
high-risk infants used to monitor SpO2
• Preterm infants very likely will need at least –– Supplemental oxygen is provided to tar-
some resuscitation, and they may develop geted preductal SpO2
complications from resuscitation more often • Infants who require resuscitation are at
than term infants risk of developing post-resuscitative
complications
Indications for resuscitation • After successful resuscitation, they require
• Apnea or poor respiratory effort placement in a setting in which close moni-
• Cyanosis toring and ongoing appropriate care can be
• Bradycardia provided
• Poor muscle tone
Withholding resuscitation
Resuscitation steps • Resuscitation efforts may be discontinued
• Initial care includes providing warmth to the after 10 min of resuscitation if the neonate
infant, clearing the airway, and drying and has demonstrated no signs of life (no heart-
stimulating the infant beat or no respiratory effort for greater than
• Apneic or gasping infant with a heart rate 10 min)
< 100 beats/min (bpm): • Resuscitation can be withheld if it is legally
–– Positive pressure ventilation (PPV) pro- acceptable and there is complete agreement
vided by bag-mask ventilation is initiated among parents and care providers that the
at a rate of 40–60 breaths/min neonatal outcome is dismal
2 Neonatology 39
NEWBORN NURSERY CARE Feeding

• Breastfed infants:
–– Should be fed as soon as possible after
Eye prophylaxis
delivery, preferably in the delivery room
• Ophthalmic erythromycin 0.5% ointment
–– Should receive at least 8–12 feeds per day
within 1 h after delivery
during the newborn hospitalization
• Prevent Neisseria gonorrhoeae ophthalmia
–– Rooming-in, skin-to-skin contact, frequent
neonatorum
demand feedings in the early postpartum
Hepatitis B prophylaxis period, and lactation support increase the
• Universal vaccination of newborns regardless rate of successful breastfeeding
of maternal hepatitis B virus surface antigen • Formula-fed infants
(HBsAg) status is recommended –– Healthy infants who are fed formula should
• The first dose of the hepatitis B vaccine be offered standard 19–20 kcal/oz. (20 kcal
(HBV) should be given within 24 h of deliv- per 30 mL) iron-containing infant formula
ery (See Chap. 1 General Pediatrics) –– Feeding on demand, but the duration
between feedings should not exceed 4 h
Vitamin K –– The volume of feedings should be at least
• Vitamin K 1 mg intramuscular (IM) injection 0.5–1 oz. (15–30 mL) per feed during the
in the first few hours after delivery prevents first few days of life
hemorrhagic disease of the newborn • Pasteurized human donor milk may be avail-
able in some nurseries for the healthy breast-
Umbilical cord care fed newborn who may require
• In developed countries where aseptic care is supplementation
routine in clamping and cutting of the umbil- • Weight loss—term infants may lose up to
ical cord, additional topical care beyond dry 10% of their BW in the first few days of life
cord care is not needed to prevent and typically regain their BW by 10–14 days
omphalitis
Hypoglycemia
Newborn screening • Glucose screening—healthy, asymptomatic
• All states in the USA require newborn screen- term infants born after an uncomplicated
ing for metabolic and genetic disorders pregnancy and delivery are at low risk for sig-
• Blood is collected for an initial screen nificant hypoglycemia. As a result, blood glu-
between 24 and 48 h of life. Some states also cose measurement is not routinely performed
require a second screen, which is usually col- in these neonates
lected between 7 and 14 days of age • Per American Academy of Pediatrics (AAP)
guidelines, glucose monitoring should be
Critical congenital heart defects screening performed for newborns with the following
• Pulse oximetry cardiac screening for all new- risk factors:
borns before discharge –– Preterm infants (infants of GA < 37 weeks)
–– Large for gestational age (LGA)
Hearing loss –– Small for gestational age (SGA)
• Universal newborn hearing screening is rec- –– Infants of diabetic mothers (IDM)
ommended to detect infants with hearing loss –– Post-term infants (GA > 42 weeks)
40 M. Fuloria
Hyperbilirubinemia MATERNAL CONDITIONS

• Visual assessment is not accurate for estimat-
ing the degree of hyperbilirubinemia remature Rupture of Membranes
P
• Use transcutaneous bilirubin or total serum
bilirubin measurement Background
• Infants should be routinely assessed every • Premature rupture of membranes (PROM)
8–12 h and at discharge for the presence of refers to a patient who is beyond 37 weeks
jaundice gestation and has presented with rupture of
• Assess pre-discharge bilirubin screen and membranes (ROM) prior to the onset of labor
risk factors together for prediction of devel- • Preterm premature rupture of membranes
opment or worsening of hyperbilirubinemia (PPROM) is ROM prior to 37 weeks
after discharge gestation
• Spontaneous preterm rupture of the mem-
24 h discharge criteria branes (SPROM) is ROM after or with the
• Full-term healthy infants between 37 and onset of labor occurring prior to 37 weeks
41 weeks gestation
• Normal spontaneous vaginal delivery • Prolonged ROM is any ROM that persists for
• Clinical course and physical examination at more than 24 h and prior to the onset of labor
discharge have not revealed abnormalities
• Stable state at least 12 h before discharge PROM at term (> 37 weeks gestation):
with normal vital signs Management
• At least two successful consecutive feedings • Evaluate the mother by speculum
• The infant has urinated regularly and passed examination
at least one stool spontaneously • Check fetal heart rate (FHR)
• Infant blood tests are available and have been • Identify fetal presentation
reviewed, such as cord or infant blood type • Most patients (90%) enter spontaneous labor
and direct Coombs test results, as clinically within 24 h when they experience ROM at
indicated term. However, most obstetricians induce
• Not at high risk to develop subsequent labor at this point. Evidence supports the idea
hyperbilirubinemia that induction of labor, as opposed to expect-
• Newborn metabolic and hearing screenings ant management, decreases the risk of chorio-
have been completed amnionitis without increasing the cesarean
delivery rate
Timing of the first well-child visit after hospital
discharge Preterm premature rupture of membranes
• For infants with a birth hospitalization less (PPROM):
than 48 h
–– An early follow-up visit is recommended Risks
within 48 h of discharge • Prematurity is the principal risk to the fetus
• For infants with a birth hospitalization greater • The risk of infection increases with the dura-
than 48 h tion of PPROM
–– An initial well-child visit within 3–5 days
after discharge is reasonable Expectant management
–– Infants at high risk of developing worsen- • The immature fetus may benefit from expect-
ing hyperbilirubinemia and breastfed ant management, even if for a short period, to
infants should be seen by their pediatrician allow for administration of steroids and
within 48 h of discharge antibiotics
2 Neonatology 41
Indications for delivery Management

• In certain circumstances (e.g., chorioamnion- • Early delivery, supportive care, and antibiotic
itis, advanced labor, fetal distress, and pla- administration
cental abruption with nonreassuring fetal • Pharmacotherapy for the mother includes:
surveillance), immediate delivery of the fetus –– Ampicillin and gentamicin
with PPROM is indicated –– Clindamycin or metronidazole when endo-
• If fetal lung maturity has been documented metritis is suspected
by either amniocentesis or collection of vagi- –– Vancomycin for penicillin-allergic patients
nal fluid, delivery should be facilitated –– Penicillin G: Used exclusively for GBS
intrapartum prophylaxis; if intraamniotic
Medications during expectant management infection is suspected, antibiotic coverage
• 48 h course of IV ampicillin and erythromy- should be broadened
cin followed by 5 days of amoxicillin and • Pharmacotherapy for the neonate
erythromycin is recommended during expect- –– Ampicillin and gentamicin
ant management • Supportive care of the neonate with sepsis
• In the absence of chorioamnionitis, some may include the following:
obstetricians give tocolysis, even with active –– Warmth, monitoring of vital signs
contractions after the steroid therapy is –– Preparedness to perform a full resuscitation,
started. The use of tocolysis should be con- including intubation and providing PPV
sidered only when a clear clinical benefit –– Treatment of hypovolemia, shock, and
exists, such as in transport of the mother to a respiratory and/or metabolic acidosis
tertiary institution with a newborn intensive –– Surfactant replacement therapy
care unit (NICU) –– Glucose homeostasis
• Magnesium sulfate given before anticipated –– Assessment and treatment of thrombocyto-
early preterm birth reduces the risk of cere- penia and coagulopathy, if present
bral palsy in surviving infants
Preeclampsia
Chorioamnionitis
Background Defined as the presence of:
• Inflammation of the fetal amnion and chorion
membranes due to a bacterial infection • Hypertension:
–– Systolic blood pressure (SBP) greater than or
Clinical presentation equal to 140 mm Hg or a diastolic blood pres-
• Maternal fever (intrapartum temperature sure (DBP) greater than or equal to 90 mm Hg
> 100.4 °F or > 37.8 °C) most frequently or higher, on two occasions at least 4 h apart
observed sign in a previously normotensive patient, or
• Significant maternal tachycardia (> 100 beats/ –– SBP greater than or equal to 160 mm Hg or
min) a DBP greater than or equal to 110 mm Hg
• Fetal tachycardia (> 160 beats/min) or higher
• Purulent or foul-smelling amniotic fluid or • Proteinuria:
vaginal discharge –– Proteinuria of ≥ 0.3 g in a 24-h urine speci-
• Uterine tenderness men, a protein (mg/dL)/creatinine (mg/dL)
• Maternal leukocytosis (total blood leukocyte ratio of ≥ 0.3, or a urine dipstick protein of
count > 15,000 cells/μL in the absence of cor- 1+ (if a quantitative measurement is
ticosteroid therapy) unavailable)
42 M. Fuloria
Preeclampsia with severe features is defined emergency setting, control of BP and seizures
as the presence of one of the following symptoms should be prioritized
or signs in the presence of preeclampsia: • Medications used for BP control include the
following:
• SBP of 160 mm Hg or higher or DBP of –– Hydralazine
110 mm Hg or higher, on two occasions at –– Labetalol
least 4 h apart while the patient is on bed rest –– Nifedipine
(unless antihypertensive therapy has previ- –– Sodium nitroprusside (in severe hyperten-
ously been initiated) sive emergency refractory to other
• Impaired hepatic function as indicated by medications)
abnormally elevated blood concentrations of –– Magnesium sulfate is the first-line treat-
liver enzymes (to double the normal ment for primary and recurrent eclamptic
concentration) seizures
• Severe persistent upper quadrant or epigastric
pain that does not respond to pharmacother-
apy and is not accounted for by alternative D iabetes Mellitus
diagnoses, or both
• Progressive renal insufficiency (serum creati- Background
nine concentration > 1.1 mg/dL or a doubling • Abnormal maternal glucose regulation occurs
of the serum creatinine concentration in the in 3–10% of pregnancies
absence of other renal disease) • Gestational diabetes mellitus (GDM) is
• New onset cerebral or visual disturbances defined as glucose intolerance with onset or
• Pulmonary edema first recognition during pregnancy
• Thrombocytopenia (platelet count < 100,000/ • GDM accounts for 90% of cases of DM in
μL) pregnancy
Risks of preexisting maternal DM on infants

Eclampsia • Growth restriction occurs with significant
frequency in pregnancies in women with pre-
• Defined as seizures that cannot be attributed existing type 1 DM
to other causes in a woman with • Double the risk of serious injury at birth, tri-
preeclampsia ple the likelihood of cesarean delivery, and
• HELLP syndrome (hemolysis, elevated liver quadruple the incidence of NICU admission
enzymes, low platelets) may complicate • Increased rate of miscarriage and birth defects
severe preeclampsia in diabetic women with suboptimal glycemic
control before conception
Management • A higher rate of congenital anomalies persists
• Delivery is the only cure for preeclampsia even with good glycemic control in the mother
• Patients with preeclampsia without severe • Anomalies involve the cardiovascular and
features are often induced after 37 weeks CNS systems; abnormalities of the skeletal,
gestation genitourinary, and gastrointestinal (GI) sys-
• In patients with preeclampsia with severe fea- tems are also seen
tures, induction of delivery should be consid-
ered after 34 weeks gestation. In these cases, Management
the severity of disease must be weighed • Insulin remains the standard medication for
against the risks of infant prematurity. In the treatment of diabetes during pregnancy, but
2 Neonatology 43
the oral agents glyburide and metformin are • Apgar score < 3 at 15 min has been associated
increasingly being used with high mortality and severe neurologic
• Mothers should keep the fasting blood sugar sequelae
value at 90–99 mg/dL, and keep 1-h, post-
meal values at < 140 mg/dL
• Before diabetic women become pregnant, Newborn Crying
they should have a glycosylated hemoglobin
• Weak cry or high-pitched cry is abnormal
(HbA1c) of < 6.5% and maintain the same
• Hoarseness can be caused by any process that
during pregnancy
affects the structure or function of the larynx
• The most common complication in a well
• Hoarse cry may indicate hypothyroidism or
controlled mother with DM is macrosomia
vocal cord paralysis
Temperature
NEWBORN EXAMINATION
• Persistent abnormal temperature in a normal
Apgar Score (Table 2.2) temperature environment must be investigated
• Hypothermia: Look for environmental fac-
• Dr. Virginia Apgar devised the Apgar score in tors, sepsis, hypoglycemia, hypothyroidism,
1952 as a simple and replicable method to low Apgar scores (hypoxia), intracranial
quickly and summarily assess the health of hemorrhage, drug withdrawal
newborn children immediately after birth • Hyperthermia: Look for environmental fac-
• The Apgar score alone cannot be considered tors (overheating from incubators, radiant
to be evidence of or a consequence of warmers or ambient environmental tempera-
asphyxia, does not predict individual neona- ture; excessive bundling or swaddling), mater-
tal mortality or neurologic outcome, and nal fever, maternal epidural anesthesia, sepsis,
should not be used for that purpose adrenal hemorrhage, or CNS disorders
• Apgar score at 1 min and 5 min does not cor-
relate well with long-term neurobehavioral
sequelae
SKIN
Table 2.2 Apgar score
• Aplasia cutis congenita (congenital absence
Score 0 1 2 of the skin):
A—Activity Absent Some flexion of Active
arms and legs
–– Absence of a portion of skin in a localized
P—Pulse Absent < 100 beats/min > 100 beats/ or widespread area at birth
(Heart rate) min –– Most commonly (70%) manifests as a soli-
G—Grimace No Grimace Cry or active tary defect on the scalp
(reflex response withdrawal –– Consider trisomy 13, especially if associ-
irritability)
A— Blue, pale Acrocyanotic Completely
ated with midline defect
Appearance pink • Acrocyanosis: Cyanosis of hands and feet
(skin color) when exposed to colder temperature; this can
R— Absent Slow and Good be a normal finding
Respiration irregular; respiratory • Generalized cyanosis: Significant hypox-
hypoventilation; effort, crying
weak cry emia (e.g., cardiac or respiratory) or
Apgar score is done at 1 min, 5 min routinely, and at 5-min intervals methemoglobinemia
thereafter until 20 min for infants with a score less than 7 • Pallor: Anemia or poor perfusion (e.g., pla-
cental abruption or placenta previa)
44 M. Fuloria
• Cutis marmorata (pale mottled skin): Cold J aundice

environment, sepsis, or hypothermia
–– While cutis marmorata is a relatively • If present on the 1st day of life, the infant
benign disorder, persistent cutis marmorata must be investigated for hemolytic anemia or
is associated with Down (trisomy 21), sepsis
Edward (trisomy 18), and Cornelia de
Lange syndromes
–– Cutis marmorata may also indicate poor
perfusion in infants developing sepsis. The HEAD
mottled appearance of the skin in cutis
marmorata usually disappears when the H ead Shape
newborn is warmed
–– The syndrome usually resolves within • Head shape and symmetry may vary, depend-
weeks to months of its presentation ing on the intrauterine position, presentation
–– No formal treatment is necessary at delivery, degree of molding, or the need for
• Plethora (very red skin): Polycythemia an instrument-assisted delivery
• Harlequin color change: Cutaneous condi- • Infants born by cesarean section often have a
tion seen in newborn babies characterized by symmetrical, round head when compared to
momentary red color changes of half the infants born vaginally whose head shape is
newborn, sharply demarcated at the body’s often elongated in the occipital area with
midline overriding sutures
• Harlequin ichthyosis: Most severe form of • Molding is temporary overlapping of bones
autosomal recessive congenital ichthyosis and must be distinguished from craniosynos-
that results in thickened keratin layer in fetal tosis. It typically resolves 2–3 days after birth
skin. The skin contains massive, diamond-
shaped plates that are separated by deep
ontanelles
F
cracks
• Ecchymoses: Usually due to birth trauma • Anterior fontanelle: Diamond shaped, open,
• Petechiae: Scattered localized petechiae are soft, and flat at birth; measures 4–6 cm at
common after delivery; however, extensive birth and usually closes at approximately
generalized petechiae must be investigated 18 months of age
for thrombocytopenia, sepsis, and other • Posterior fontanelle: Usually triangular,
causes < 0.5 cm at birth and closes shortly after birth:
–– Hypothyroidism must be considered if
posterior fontanelle is persistently opened
ubcutaneous Fat Necrosis
S
• Bulging fontanelle can be normal in a crying
of the Newborn (SCFN) infant, but may be associated with hydro-
cephalus, birth injury, intracranial bleeding,
• Uncommon disorder characterized by firm,
or infection. It may be present as a late sign of
mobile, erythematous nodules and plaques
increased intracranial pressure
over the trunk, arms, buttocks, thighs, and
• Large fontanelles may indicate hypothyroid-
cheeks of full-term newborns
ism, hydrocephaly, in utero malnutrition,
• Self-limited process that usually does not
rickets, or a genetic disorder
require treatment
• Depressed anterior fontanelle is a late sign
• May be complicated by hypercalcemia and
of dehydration
other metabolic abnormalities
2 Neonatology 45
Caput Succedaneum • Can extend to orbits and neck

• Usually secondary to rupture of emissary
• Definition: Diffuse subcutaneous edematous veins
swelling of soft tissue of the scalp that may • If massive, coagulopathy may be present
extend across the suture lines
• Causes: Secondary to the pressure of the Management
uterus or vaginal wall • Progressive after birth but typically resolves
• Outcome: Usually resolves within 48–72 h within 2–3 weeks
• Monitor BP, hematocrit, bilirubin, and signs
for hypovolemia, bleeding, and shock
Cephalohematoma
Background
• Subperiosteal hemorrhage that is soft, fluctu- raumatic Epidural, Subdural,
T
ant, cyst-like swelling with a well-defined and Subarachnoid Hemorrhage
outline
• Initially firm but becomes more fluctuant Risk factors
after 48 h • Large head
• Typically calcifies at the edges during • Prolonged labor in breech or precipitous
resolution delivery
• Cephalohematoma never extends across
suture line Important
• Child abuse must be suspected in all infants
Causes with subdural hemorrhage after the immedi-
• Difficult or instrument-assisted delivery ate neonatal periods
Management Diagnosis
• Radiograph or computed tomography (CT) • Suspect subdural hemorrhage if megaloceph-
scan should be obtained if skull fracture is aly, bulging fontanel, unexplained anemia
suspected and jaundice, or seizures
• Hemoglobin and bilirubin should be • CT scan and magnetic resonance imaging
monitored (MRI) are useful in the diagnosis
• Most cephalohematomas resolve within
2–3 weeks to several months
Skull Fractures
• Linear fracture: Linear fractures are benign
Subgaleal Hemorrhage and have excellent prognosis
• Depressed fracture: Ping-pong ball, usually
Background not associated with loss of bone continuity;
• Serious but less common complication, usu- prognosis is good if neurological exam is
ally associated with vacuum-assisted normal
delivery • Basilar fracture: Overall prognosis is
• Collection of blood between the aponeurosis guarded and there is significant risk of perma-
and the periosteum nent sequelae
46 M. Fuloria
EYES young child, includes epiphora, photophobia,

and blepharospasm. The cornea is enlarged
• Red reflex examination: and becomes progressively cloudy. A corneo-
–– Dark spots in the red reflex, a blunted red scleral junction more than 12 mm in diameter
reflex on one side, lack of a red reflex, and in the 1st year of life is highly suggestive of
the presence of a white reflex are all indica- glaucoma
tions for immediate ophthalmology
referral
–– White pupillary reflex (leukocoria):
Cataract, retinoblastoma, retinopathy of
EARS
prematurity, retinal coloboma, Coats dis- • Malformed ears and low set ears are associ-
ease, persistent fetal vasculature ated with many syndromes, look for urogeni-
–– Cataract: Galactosemia, intrauterine infec- tal malformation
tions (rubella); can be inherited as a domi- • Preauricular pits and tags: Renal ultra-
nant trait from an affected parent sound should be performed in any newborn
• Coloboma (hole in the structure of the eye with an ear anomaly accompanied by other
such as the lens, iris, retina, choroid, or optic dysmorphic features, family history of deaf-
disc) ness, maternal history of gestational diabetes,
–– CHARGE syndrome (Coloboma, Heart or a defined syndrome
defect, Choanal atresia, Retarded growth
and development, Genital abnormality, Ear
abnormality), and trisomy 13 (Patau
NOSE
syndrome)
• Brushfield spots: Small white spots on the • Nasal stuffiness after birth can be a sign of
surface of the iris arranged in a concentric drug withdrawal
ring around the pupil; seen in healthy chil- • Choanal atresia can be unilateral or bilateral
dren but are far more common in patients (respiratory distress and cyanosis while feed-
with Down syndrome ing if bilateral)
• Strabismus: Persistent strabismus must be • Snuffles (rhinorrhea) and saddle nose:
referred immediately; occasional eye devia- Usually associated with syphilis
tion can be normal in the first 4 months of life • Flattened nasal bridge: Can be a normal
• Eyelids: Ptosis could be a sign of Horner variant or associated with congenital syphilis,
syndrome or congenital myasthenia gravis. Down syndrome, or Williams syndrome
Check maternal history (for congenital myas-
thenia); check the arms and the clavicles
• Subconjunctival hemorrhage: Secondary
to rupture of small blood vessels near the sur- MOUTH
face of the bulbar conjunctiva. Can occur nor-
mally during labor and delivery and resolves • Epstein pearls: Small, opaque whitish-yel-
spontaneously over a period of time low papules that are firm in consistency and
• Blue sclera: Osteogenesis imperfecta or nor- are located on the mid-palatal raphe at the
mal variant junction of the hard and soft palate (Fig. 2.1)
• Congenital glaucoma: The classic triad of –– Represents keratin entrapment within the
manifestations, any one of which should soft and hard palate
arouse suspicion of glaucoma in an infant or –– Common and benign finding
2 Neonatology 47
• High arched palate: Usually associated with

syndromes
• Pierre Robin sequence: Triad of retrogna-
thia or micrognathia, glossoptosis, and air-
way obstruction
• Cleft lip and palate: Can be hereditary or
associated with syndromes
• Macroglossia: Can be congenital or acquired;
associated with hypothyroidism, Beckwith-
Wiedemann syndrome, Pompe disease, and
Down syndrome
Natal teeth
Fig. 2.1 Infant with Epstein pearl in the hard palate • Supernumerary: Usually very loose and
easy to remove with a little pinch
• True milk teeth: Usually hard and should
not be removed (Fig. 2.3)
Ankyloglossia or tongue-tie
• Caused by a short frenulum on the underside
of the tongue that prevents complete protru-
sion of the tongue
• Can interfere with breastfeeding and speech
articulation
• Frenulotomy is recommended if interfering
with feeding or speech
Fig. 2.2 Infant with Bohn nodules in the upper gums
• Bohn nodules: Grayish-white, firm nodules

frequently present on the buccal or lingual
aspects of the alveolar ridges (Fig. 2.2)
–– Exact etiology is unknown, but they are
thought to arise from remnants of the den-
tal lamina or from heterotopic salivary
glands
–– Benign finding that will disappear with
time
• Ranula: Translucent, firm papule or nodule
found on the anterior floor of mouth, lateral to Fig. 2.3 Infant with two true milk lower central incisor
lingual frenulum teeth, hard to move
48 M. Fuloria
NECK –– Moro response is asymmetrical, with no

active abduction of the ipsilateral arm
Brachial Plexus Injuries (BPI) –– Horner syndrome (i.e., miosis, ptosis, anhi-
drosis) may occur, a bad prognostic sign
Background usually associated with avulsion injury
• Erb’s palsy (Duchenne-Erb palsy): Upper –– Respiratory distress and elevation of dia-
trunk nerve injury (C5 and C6, ±C7), due to phragm may occur due to injury to phrenic
traction on the upper trunk; most common nerve
form • Erb’s palsy (C5-C6, ±C7)
• Klumpke palsy: Injury to the C8-T1 nerve –– Arm adducted and internally rotated; elbow
roots; results in weakness of the hand mus- extended and the forearm pronated; wrist
cles, absent grasp, and sometimes Horner flexed and the hand in a fist (waiter tip
syndrome position)
• Total brachial plexus injury involves both –– Absent Moro reflex, but grasp reflex is
upper and lower roots present on the affected side
• Most patients have the least severe form of –– In the 1st hours of life, the hand may appear
nerve injury (neuropraxia) and recover spon- flaccid, but strength soon returns
taneously or with supportive physical –– About 80% of patients with Erb’s palsy
therapy will show complete recovery within the
first 3 months, 90% recover by 12 months
Classification • Klumpke palsy (C8-T1)
• Purely neurapraxic lesions –– Rare
–– Stretching of nerve without disruption –– Absent grasp reflex on affected side
–– These lesions generally are reversible and –– Supinated arm, elbow bent, wrist extended,
do not leave sequelae and fingers flexed, “claw hand”
• Axonotmetic lesions –– One-third of cases associated with Horner
–– Due to nerve fibers (axons) disruption with syndrome
intact sheath –– Phrenic nerve injuries may be evident
–– Cause degeneration of the axon distal to
the injury Associated injuries
–– These injuries improve gradually over • The pediatrician must perform a careful
4–6 months, depending on the level of the examination of the infant with BPI to look for
lesion associated injuries
• Neurotmesis lesions • The most common associated (not causative)
–– The most severe form injuries:
–– Involves disruption of the axon and myelin –– Clavicular and humeral fractures
sheath (total severing, avulsion injury) –– Torticollis
–– Muscle atrophy from a neurotmesis lesion –– Cephalohematoma
begins 3–6 months after injury, and com- –– Facial nerve palsy
plete recovery is impossible (worst –– Diaphragmatic paralysis
prognosis)
Diagnosis
Clinical presentation • Chest radiography: Look for clavicular frac-
• Complete brachial plexus palsy (C5-T1) tures or elevation of diaphragm suggesting
–– Arm held limp at side phrenic nerve injuries and root avulsion
–– Deep tendon reflexes (DTRs) in the • High-resolution MRI is the study of choice
affected arm are absent for evaluating brachial plexus injuries
2 Neonatology 49
• MRI is indicated for preoperative planning in

severe cases requiring surgery
Management
• Rehabilitation must start immediately after
the diagnosis. Treatment is directed towards
preventing contractures:
–– Intermittent and partial immobilization:
The arm can be fixed across the child’s
chest by pinning of his/her clothing to pro-
vide more comfort
–– Active and passive range of motion
exercises
–– Dress the infant gently and avoid further
Fig. 2.4 Three-week-old infant with enlarged breast tissue,
traction on the arm resolved spontaneously after several weeks
–– Wrist extension splint is necessary to main-
tain proper wrist alignment and to reduce
the risk of progressive contractures
LUNG
–– Assessments every 3–4 weeks are
indicated Respiratory distress
• Persistence of symptoms beyond 1 month of • Normal respiratory rate is 40–60 breaths/min
age suggests that the injury may require • Respiratory rate persistently more than
treatment 60 breaths/min in the newborn period is
• Absence of full recovery by age of 3 months, abnormal
signs of root avulsion (Horner syndrome, • Grunting, nasal flaring, retractions, and tachy-
phrenic nerve involvement), total palsy, and pnea may be transient in the first few hours
Klumpke palsy are all indications for referral after birth—transient tachypnea of the new-
to orthopedics born (TTN). If it persists for more than 24 h,
other causes must be explored
Unilateral movement of the chest

CHEST • Phrenic nerve palsy
• Diaphragmatic hernia
• Fracture of the clavicle is very common; Cough
crepitation usually found during • Always abnormal in newborn
examination • Pneumonia must be considered
• Supernumerary nipple (polythelia) is fairly
common and considered minor anomaly
• Pectus excavatum is a congenital depression HEART
of the sternum and is usually insignificant
• Widely spaced nipples are seen in Turner • Point of maximal cardiac impulse (PMI):
syndrome Location is fourth to fifth intercostal space
• Breast hypertrophy and galactorrhea may be just medial to left mid-clavicular line
seen in both male and female infants (because • If PMI is displaced, chest radiograph is recom-
of maternal hormones); engorgement may mended to rule out pneumothorax, dextrocar-
increase during the first few days but then dia, diaphragmatic hernia, or space-occupying
usually resolves (Fig. 2.4) lesion
50 M. Fuloria
• Bradycardia: HR < 100 bpm is abnormal. Abdominal Masses

Look for sepsis, asphyxia, increased intracra-
nial pressure, hypothyroidism, congenital • Multicystic dysplastic kidney is the most
heart disease, and heart block (as may be seen common cause of an abdominal mass in the
in infants born to mothers with systemic lupus newborn period and is the most common cys-
erythematosus) tic malformation of the kidney in infancy
• Tachycardia: HR > 180 bpm. Look for fever, • Subcapsular hematoma of the liver (traumatic
hypovolemia, anemia, tachyarrhythmia, delivery)
hyperthyroidism, and drug withdrawal
Abdominal Wall Defects

Murmur
• Approximately 60% of infants will have a • Umbilical hernia and diastasis recti
murmur auscultated in the newborn period –– Usually benign and self-limited conditions
• Most murmurs in the neonatal period are –– Umbilical hernias are managed with obser-
benign. Benign murmurs are usually due to vation, as these defects typically close by
transient changes in the postnatal circulation age 4 or 5 years (Fig. 2.5)
(e.g., patent ductus arteriosus) –– Any defects that persist beyond this age or
• 8% of murmurs at birth are associated with the defect is larger than 2 cm should
congenital heart disease undergo surgical repair
• Murmurs usually require workup if the fol- • Omphalocele
lowing are present: –– Result of herniation of the intestine and
–– Persist after the first day of life other abdominal organs into the umbilical
–– Presence of cyanosis cord without returning into the abdominal
–– Evidence of poor perfusion cavity
–– Poor feeding –– The abdominal viscera are contained in a
translucent sac, which is composed of
Blood pressure amnion, Wharton jelly, and peritoneum
• SBP in term infants < 12 h usually between –– The umbilical vessels insert into the wall
60 and 90 mmHg of the sac, and not the abdominal wall
• BP in right arm and one leg must be deter-
mined; a pressure difference of more than
20 mmHg in favor of the arms may be consid-
ered evidence of coarctation of the aorta
• Absent/weaker pulse in the lower extremities
is a red flag for coarctation of the aorta
ABDOMEN
Liver/Spleen
• Liver is normally palpated 1–2 cm below the
right costal margin in the newborn
• Spleen is normally palpable not more than
1 cm below the left costal margin Fig. 2.5 Infant with a large umbilical hernia
2 Neonatology 51
–– Associated with syndromes and chromo- • Umbilical granuloma

somal abnormalities in > 50% of cases, –– Granulation tissue may persist at the base
including Beckwith-Wiedemann syndrome of the umbilicus after cord separation
(omphalocele, macroglossia, organomeg- –– Surface of an umbilical granuloma may be
aly, hypoglycemia, and increased risk of smooth or irregular and is often
childhood tumors such as Wilms tumor, pedunculated
neuroblastoma, and hepatoblastoma) –– The tissue is composed of fibroblasts and
• Gastroschisis capillaries and can grow to more than
–– Considered to be the result of a vascular 1 cm
accident of the omphalomesenteric artery, –– Small granulomas may be treated ade-
a failure of mesoderm formation, rupture quately with applications of topical silver
of the amnion around the umbilical ring nitrate. Larger granulomas or those refrac-
with herniation of the midgut, or abnormal tory to silver nitrate may require surgical
involution of the right umbilical vein with resection
body wall weakening –– Umbilical granulomas must be differenti-
–– Full thickness defect in the abdominal wall ated from umbilical polyps, which do not
with prolapse of the intestine through the respond to silver nitrate cauterization
defect • Omphalomesenteric duct remnants
–– No covering membrane on the defect –– Persistence of all or portions of the ompha-
–– Defect lies to the right of an intact umbili- lomesenteric duct can result in fistulas,
cal cord sinus tracts, cysts, congenital bands, and
• Prune belly syndrome (Eagle-Barrett mucosal remnants. The most common
syndrome) remnant is a Meckel diverticulum
–– Caused by laxity of the abdominal –– Patients with mucosal remnants can pres-
musculature ent with an umbilical polyp or an umbilical
–– Wrinkly folds of skin covering the cyst
abdomen –– The condition should be suspected in cases
–– Associated with GI and genitourinary tract of delayed separation of the cord or persis-
anomalies (obstructive uropathy) and pul- tent, large, umbilical granulomas with
monary hypoplasia associated drainage
–– Undescended testis in males • Delayed separation of the umbilical cord
• Urachal remnants –– The umbilical cord usually separates and
–– The urachus is a structure that connects the sloughs by the end of the second postnatal
dome of the bladder to the anterior abdom- week
inal wall at the level of the umbilicus –– Cord care involves keeping the area clean
–– With a patent urachus, a complete commu- and dry
nication between the bladder and umbili- –– A marked delay in cord separation raises
cus remains. Urine is noted to drain from the suspicion of leukocyte adhesion defi-
the umbilicus ciency (LAD), a rare disorder leading to
–– Remnants of this connection include a pat- defective neutrophil function
ent urachus, urachal sinus (free communi- • Single umbilical artery (SUA)
cation between the bladder and umbilicus), –– The normal umbilical cord has one vein
and urachal cyst and two arteries
–– Umbilical polyps can be observed in asso- –– SUA occurs in up to 2% of all live-born
ciation with a urachal remnant infants
52 M. Fuloria
–– SUA is thought to result from either apla- • Chordae: The skin on the underside of the
sia or atrophy of the second umbilical penis may be tethered to the scrotum, called
artery or from persistence of the normally chordae; this may be associated with
transient early embryonic SUA hypospadias
–– Associated structural or chromosomal • Hypospadias: Defect of the urethra in a male
anomalies are seen in 27% of infants with infant that involves an abnormally placed ure-
SUA, with renal malformations being the thral meatus. Instead of opening at the tip of
most common finding the glans, the urethra opens anywhere along a
–– A newborn with SUA should be examined line running from the tip along the ventral
thoroughly for dysmorphic features, aspect of the shaft to the junction of the penis
abdominal masses, and the presence of and the perineum
heart disease –– Infants with hypospadias should not be cir-
–– SUA is associated with an increased risk of cumcised because the foreskin is often
chromosome abnormalities such as trisomy used during surgical repair
13, trisomy 18, and triploidy • Epispadias: Meatal opening is on the dorsal
surface of the penis. It is less common than
hypospadias
• Mispositioned meatus: May be associated
GENITALIA with urethral or kidney abnormalities and
may result in poor urinary stream
Females
Testis
• Female infants have two orifices, one for the • Normally in the scrotum in term infants but
urethra just below the clitoris and the other may be palpated in the upper scrotum or in
for the vagina. The urethral orifice must be the inguinal canal
differentiated from the vagina • Cryptorchidism occurs in 3–5% of term
• Infants can have a creamy white to slightly male infants
blood-tinged discharge 2–3 days after birth, –– Undescended testicles may be true unde-
caused by withdrawal of maternal hormones scended testicles, ectopic testicles, or
• Imperforate hymen can result in hydrometro- retractile testicles
colpos, which usually presents as a bulging • Discoloration of the scrotum may be pres-
hymen especially with crying, or an abdomi- ent in a neonate born after breech presenta-
nal mass tion or may be caused by testicular torsion or
hematoma
• Testicular torsion can occur in infancy and
Males presents as an enlarged testicle with overly-
ing discoloration of the scrotum
Penis
• Term infant’s penile length is 2.5–3.5 cm
• Micropenis: Penile length < 2.5 cm is abnor- A mbiguous Genitalia (See Also
mal (hormonal workup is needed). Infants Chap. 12 Endocrinology)
should be observed for evidence of metabolic
derangements • Small penis, bifid scrotum, large clitoris, and
• Prepuce is usually adherent and should not be pigmented fused vulva are signs of ambigu-
forcibly retracted ous genitalia
2 Neonatology 53
• Initial screening • Indication for ultrasound or MRI

–– Chromosomal analysis –– Multiple dimples
–– Endocrine screening –– Dimple diameter more than 5 mm
–– Serum chemistries/electrolyte tests (possi- –– Dimple > 2.5 cm above the anus (the higher
ble CAH) the lesion, the higher the risk)
–– Androgen-receptor levels –– Dimple outside the sacrococcygeal region
–– 5-Alpha reductase type II level –– Marked by a tuft of hair, skin discoloration,
–– Abdominal ultrasound to evaluate for the or skin tag
presence of ovaries/uterus vs. testicles –– Base of the dimple cannot be visualized
–– Genetic and endocrinology consultations • Indications for referral to neurosurgery
–– Abnormal ultrasound or MRI, e.g., occult
spinal dysraphism; split cord malforma-
Anus tion, dermal sinus tract, tethered spinal
cord, and intraspinal lipoma
• The anus should be examined carefully to –– Other associated cutaneous findings, e.g.,
confirm it is not just a fistula hypertrichosis and hemangioma
• Presence of meconium does not rule out –– Abnormal neurologic examination
imperforate anus; meconium may pass from
the fistula
• Position of the anus should be determined
–– Mild mislocation of the anus may be associ- EXTREMITIES
ated with constipation later in life
• Meconium usually passes in the first 24 h of Developmental dysplasia of the hip (DDH)
birth and 99% of term infants will pass meco- • Ortolani and Barlow tests (See also Chap. 13
nium within the first 48 h Orthopedics) must be performed for all new-
• Impaction of meconium that causes intestinal borns before discharge from the newborn
obstruction is often associated with cystic nursery
fibrosis (CF)
Hemihypertrophy
• Wilms tumor occurs in association with either
isolated hemihypertrophy of the extremities
BACK or Beckwith-Wiedemann syndrome
Polydactyly
Sacral dimple
• Ulnar or postaxial polydactyly
• A pilonidal sinus (sacral dimple) may be
–– The most common and usually isolated
present at the base of the spine between the
condition
buttocks
–– Postaxial polydactyly more common than
–– Typically, benign
pre-axial polydactyly
–– Rarely, a true sinus tract associated with a
–– Usually autosomal dominant with incom-
myelomeningocele may be present
plete penetrance
–– May be associated with a tethered cord
• Radial or preaxial polydactyly
• Abnormal pigmentation, overlying hemangi-
–– Usually syndromic and associated with
oma, pigmented nevus, or a hair tuft over the
other anomalies
lower spine may be associated with vertebral
anomalies Assessment of gestational age (Table 2.3)
54 M. Fuloria
Table 2.3 Gestational age ranges according to the physical characteristics of newborn and maturity
Body parts Characteristics Weeks of gestation range
Vernix (waxy or cheese-like white Coat the entire body < 38 weeks
substance found coating the skin of Less coated areas 38–39 weeks
newborn babies) Scant 40–41 weeks
No vernix > 42 weeks
Lanugo (very fine, soft, unpigmented, Covers most of the body < 32 weeks
downy hair covers the body of a newborn) Disappears from face 33–37 weeks
Present on shoulders only 38–41 weeks
None present ≥ 42 weeks
Testes Palpable in inguinal canal < 36 weeks
Palpable in upper scrotum 36–39 weeks
Palpable in lower scrotum ≥ 40 weeks
Scrotum Few rugae < 36 weeks
More rugae 36–39 weeks
Rugae all over the scrotum 40–41 weeks
Pendulous scrotum ≥ 42 weeks
Labia and clitoris Prominent clitoris and labia minora Preterm
Labia majora is prominent Full-term
Sole creases No anterior sole creases < 32 weeks
1–2 anterior creases 32–33 weeks
2–3 anterior creases 34–35 weeks
2/3 of the anterior sole with creases 36–37 weeks
Heel creases present 38–41 weeks
Deeper creases over entire sole ≥ 42 weeks
• Maternal factors
NEONATAL CONDITIONS –– Chronic diseases—hypertension, chronic
renal disease, systemic lupus erythemato-
I ntrauterine Growth Retardation sus, DM
(IUGR) –– Preeclampsia early in gestation
–– Smoking, drugs, and alcohol
Definition –– Constitutionally small mother
• IUGR, which is defined as less than 10% of –– Malnutrition
predicted fetal weight for GA, may result in • Placental factors
significant fetal morbidity and mortality –– Placental infarction
• Second leading cause of perinatal mortality –– Small placenta
–– Chronic vascular disease
Causes –– Uteroplacental insufficiency
• Fetal factors:
–– Chromosomal abnormalities (aneuploidy) Symmetrical (proportional) vs. asymmetrical
–– Multifactorial congenital malformations— (relative head sparing) IUGR
cardiovascular abnormalities, renal agenesis • Symmetrical IUGR results from an early
–– Multiple gestation fetal insult caused by chemical exposure (e.g.,
–– Infections: Congenital cytomegalovirus, nicotine from cigarette smoking), viral infec-
toxoplasmosis, herpes simplex virus tion, or inherent developmental abnormalities
(HSV), rubella caused by aneuploidy
–– Aberrant genomic imprinting—uniparen- • Asymmetrical IUGR is likely to result from
tal disomy uteroplacental insufficiency
2 Neonatology 55
Diagnosis I nfant of Diabetic Mother (IDM)

• Although no single biometric or Doppler
measurement is completely accurate for help- Background
ing make or exclude the diagnosis of growth • About 3–10% of pregnancies are affected by
restriction, screening for IUGR is important abnormal glucose regulation and control. Of
to identify at-risk fetuses these cases, 80–88% are related to abnormal
glucose control of pregnancy or gestational
DM
Multiple Births • Hyperglycemia during pregnancy causes fetal
hyperglycemia and fetal hyperinsulinemia
Definition • Fetal congenital malformations are most
• Multiple births occur when multiple fetuses common when maternal glucose control has
are carried during a pregnancy with the sub- been poor during the first trimester of
sequent delivery of multiple neonates pregnancy
• Preconceptional glycemic control in women
Types
with diabetes cannot be overstated
• Dizygotic twins develop when two ova are
• Maternal hyperglycemia during late gestation
fertilized; dizygotic twins have separate
is more likely to lead to fetal macrosomia,
amnions, chorions, and placentas
hypoxia, polycythemia, and cardiomegaly
• Monozygotic twins develop when a single
with outflow tract obstruction
fertilized ovum splits after conception. An
early splitting (i.e., within 2–3 days after fer- Complications
tilization) of monozygotic twins produces • Fetal macrosomia
separate chorions and amnions (dichorionic –– Weight > 90th percentile for GA or
diamniotic). Monochorionic monoamniotic > 4000 g in the term infant occurs in
twins occur when the split takes place after 15–45% of diabetic pregnancies
the ninth day after fertilization. Cleavage of –– Most commonly observed as a conse-
the fertilized ovum between days 4 and 8 of quence of maternal hyperglycemia and
fertilization results in monochorionic diamni- fetal hyperinsulinemia
otic twins –– Infant may appear puffy, fat, ruddy, and
often hypotonic
Associated complications
–– LGA infants should be routinely screened
• Premature delivery
for hypoglycemia
• Malpresentation
• Impaired fetal growth
• Congenital abnormalities
–– Infants whose BW is below the tenth per-
• Umbilical cord compression and cord
centile are considered SGA
entanglement
–– Impaired fetal growth may occur in as
• Placental abruption
many as 20% of diabetic pregnancies
• Twin-twin transfusion syndrome
–– Maternal renovascular disease is a com-
• Fetal growth restriction
mon cause of impaired fetal growth in
• Conjoined twins
pregnancies complicated by maternal
–– Occur only in monoamniotic, monochori-
diabetes
onic twins
–– Perinatal asphyxia is more common in
–– Occur in 1/50,000 births
infants with impaired fetal growth
56 M. Fuloria
• Pulmonary disease • Thrombocytopenia

–– IDM are at increased risk of respiratory • Cardiovascular anomalies
distress syndrome that may present within –– Cardiomyopathy with ventricular hyper-
the first few hours after birth with tachy- trophy and outflow tract obstruction may
pnea, nasal flaring, intercostal retractions, occur in as many as 30% of IDMs
and hypoxia ◦◦ Cardiomyopathy may be associated with
–– Transient tachypnea of the newborn congestive failure with a weakly func-
–– Persistent pulmonary hypertension of tioning myocardium or may be related
newborn secondary to polycythemia may to a hypertrophic myocardium with sig-
occur nificant septal hypertrophy and outflow
• Metabolic and electrolyte abnormalities tract obstruction
–– Hypoglycemia is caused by hyperinsu- –– Echocardiography is indicated if cardio-
linemia due to hyperplasia of fetal pancre- megaly or hypoperfusion are present
atic beta cells consequent to maternal-fetal –– Increased risk of congenital heart defects,
hyperglycemia including (most commonly) ventricular
–– Hypoglycemia may present within the first septal defect (VSD) and transposition of
few hours of life and may persist for as the great arteries (TGA)
long as a week • Congenital malformations
–– Infant may present with no symptoms –– CNS malformations are 16 times more
–– Jitteriness, irritability, apathy, poor feed- likely in IDMs
ing, high pitched or weak cry, hypotonia, ◦◦ Risk of anencephaly is 13 times higher
or frank seizure activity may occur ◦◦ Risk of spina bifida is 20 times higher
• Hypocalcemia or hypomagnesemia –– Sacral agenesis; the risk of caudal dyspla-
–– Symptoms may include jitteriness or sei- sia is up to 600 times higher in IDM
zure activity –– Increased risk of renal abnormalities—
–– Hypocalcemia (levels < 7 mg/dL) is hydronephrosis, renal agenesis, and ure-
believed to be associated with a delay in teral duplication
parathyroid hormone synthesis after birth –– Increased risk of GI abnormalities—small
• Iron deficiency left colon syndrome, and duodenal or ano-
–– 5% of all IDMs demonstrate abnormalities rectal atresia
of iron metabolism at birth
–– Iron deficiency increases the infant’s risk
for neurodevelopmental abnormalities anagement of Hypoglycemia
M
• Polycythemia
–– Caused by increased erythropoiesis trig- • Screening policy for hypoglycemia after birth
gered by chronic fetal hypoxia is necessary to detect hypoglycemia
–– Clinically presents as “ruddy” appearance, • Initial feed within 1 h; screen glucose within
sluggish capillary refill, or respiratory 30 min
distress • Asymptomatic infant; birth—4 h of age:
–– Hyperviscosity due to polycythemia –– If initial blood glucose value is < 25 mg/dL
increases the risk for stroke, seizure, necro- –– Refeed and check blood glucose in 1 h
tizing enterocolitis, and renal vein –– If blood glucose is still < 25 mg/dL, imme-
thrombosis diate IV with 2 mL/kg infusion of 10%
• Hyperbilirubinemia dextrose followed by continuous infusion
–– Common, especially in association with of dextrose at an infusion rate of 5–8 mg/
polycythemia kg/min
2 Neonatology 57
◦◦ Failure to start maintenance dextrose • Unbound unconjugated bilirubin can cross

infusion may result in rebound hypogly- the blood-brain barrier and is toxic to the
cemia as a result of heightened pancre- CNS
atic insulin release triggered by the • Once unconjugated bilirubin reaches the
glucose infusion liver, it is conjugated by uridine diphosphate
◦◦ Once the infant’s glucose levels have glucuronosyl transferase (UGT1A1)
been stable for 12 h, IV glucose may be • Hepatic UGT1A1 increases dramatically in
tapered by 1–2 mg/kg/min the first few weeks after birth
◦◦ Achieve plasma glucose of 45–50 mg/dL • At 30–40 weeks gestation, UGT1A1 values
–– If blood glucose level is 25–40 mg/dL: are approximately 1% of adult values, rising
◦◦ Refeed; provide IV dextrose as needed to adult concentrations by 14 weeks of age
• Asymptomatic infant; 4–24 h of age: • Conjugated (direct) bilirubin is excreted into
–– Continue feeds every 2–3 h the intestine via the gallbladder and bile duct
–– If blood glucose is < 35 mg/dL: • Bacteria in the intestine can deconjugate bili-
◦◦ Refeed and check blood glucose in 1 h rubin, allowing it to be reabsorbed into the
◦◦ If blood glucose is still < 35 mg/dL, blood. The rest of the bilirubin is excreted
immediate IV therapy with 2 mL/kg with the stool
infusion of 10% dextrose followed by
continuous infusion of dextrose at an
infusion rate of 5–8 mg/kg/min hysiologic Jaundice
P
–– If blood glucose is 35–45 mg/dL, refeed;
provide IV dextrose as needed Background
–– Provide IV dextrose if infant develops • Unconjugated hyperbilirubinemia that occurs
symptoms of hypoglycemia after the first postnatal day
–– Jaundice that is visible during the first day
of life is pathologic
Hyperbilirubinemia – – Infants who present with jaundice after
3–4 days of life may also require closer
• Jaundice occurs in approximately 60% of scrutiny and monitoring
neonates born yearly in the USA –– In infants with severe jaundice or jaundice
• Most common condition that requires medical that continues beyond the first 1–2 weeks
attention and hospital readmission in newborns of life:
◦◦ Check for galactosemia and congenital
Pathophysiology hypothyroidism in newborn metabolic
• Hemolysis of RBCs→hemoglobin is released screen results
• Biliverdin is formed from heme through the ◦◦ Explore family history
action of heme oxygenase ◦◦ Evaluate infant’s weight curve
• Biliverdin reductase reduces biliverdin to ◦◦ Elicit mother’s impressions of the ade-
unconjugated (indirect) bilirubin quacy of breastfeeding
• Unconjugated bilirubin binds to albumin ◦◦ Assess stool color
and is transported to the liver • It can last up to 1 week
• Unconjugated bilirubin can become • Total serum bilirubin (TSB) concentration
unbound if albumin is saturated or if bilirubin peaks in the first 3–5 postnatal days in term
is displaced from albumin by medications infants
(e.g., sulfisoxazole, streptomycin, chloram- • A decline to adult values over the next several
phenicol, ceftriaxone, ibuprofen, salicylates) weeks
58 M. Fuloria
• TSB concentrations vary greatly in infants, • Cephalohematoma or significant bruising

depending on race, type of feeding, and • Poor feeding
genetic factors • Exclusive breastfeeding
• East Asian race (defined by mother’s descrip-
Physiologic jaundice occurs in infants for a tion) or Mediterranean descent
number of reasons: • Jaundice observed before discharge
• Increased breakdown of fetal erythrocytes • Macrosomic infant of a diabetic mother
due to: • Male gender
–– Shortened lifespan of fetal erythrocytes
(70–90 days)
–– Higher erythrocyte mass in neonates arly Onset Breastfeeding Jaundice
E
• Hepatic excretory capacity is low because of:
–– Low concentrations of the binding protein Background
ligandin in the hepatocytes • Early onset breastfeeding jaundice (manifests
–– Low activity of glucuronyl transferase, the in the first 3 days of life) is the most common
enzyme responsible for binding bilirubin cause of unconjugated hyperbilirubinemia
to glucuronic acid, thus making bilirubin
water soluble (conjugation) Causes
–– Thus, neonates have a high rate of bilirubin • Breastfeeding exaggerates physiologic jaun-
production and an impaired ability to dice in the first postnatal week because of
extract bilirubin from the body caloric deprivation, leading to an increase in
enterohepatic circulation
Clinical presentation • Mild dehydration and delayed passage of
• Jaundice meconium also plays roles
• The TSB concentration peaks at approxi-
mately 5.5 mg/dL (94.1 μmol/L) by the third Prevention
postnatal day in white and African American • Successful breastfeeding decreases the risk of
infants hyperbilirubinemia
• By 96 h of age, 95% of infants have TSB con- • Infants need to be fed at least 8–12 times in
centrations of < 17 mg/dL the first few days after birth to help improve
• Bilirubinemia > 17 mg/dL is not physiologic the mother’s milk supply
• The best way to judge successful breastfeed-
Risk factors for development of severe hyper- ing is to monitor infant urine output, stool
bilirubinemia in newborns > 35 weeks GA output, and weight
• Jaundice observed in the first 24 h of age • Newborns should have four to six wet diapers
• Predischarge TSB or transcutaneous bilirubin and three to four yellow, seedy stools per day
in the high-risk zone by the fourth day after birth
• Blood group incompatibility (ABO or Rh) • Breastfed infants should lose no more than
with positive direct antiglobulin test; other 10% of their body weight by the third or
known hemolytic disease such as glucose- fourth postnatal day
6-phosphate dehydrogenase deficiency • Formula supplementation may be necessary if
• GA of 35–36 weeks the infant has significant weight loss, poor urine
• Previous sibling requiring phototherapy output, poor caloric intake, or delayed stooling
2 Neonatology 59
• Water and dextrose solutions should not be J aundice in Premature Infants

used to supplement breastfeeding because
they do not prevent hyperbilirubinemia and • Hyperbilirubinemia is more common and
may lead to hyponatremia more severe in preterm infants and lasts
longer
• Sick preterm newborns are more likely to
Late Onset Breast Milk Jaundice have a delay in initiating enteral nutrition,
resulting in an increase in enterohepatic
Background circulation
• Thought to be a normal exaggeration of phys- • Kernicterus is extremely uncommon; how-
iologic jaundice in human milk fed infants ever, kernicterus does occur at lower TSB
• Indirect hyperbilirubinemia that develops in concentrations, even without acute neuro-
an otherwise healthy breastfed newborns logic signs
after the first 4–7 days of life and may persist • TSB values as low as 10–14 mg/dL (171.0–
for 6–12 weeks 239.5 μmol/L) have resulted in milder forms
• Exact mechanism is not entirely clear of bilirubin-induced neurologic dysfunction
• It is suggested that beta-glucuronidases and nonin preterm infants
esterified fatty acids in the human milk inhibit • Initiation of phototherapy according to the
enzymes that conjugate bilirubin in the liver weight of infants and associated complica-
tions is paramount (Table 2.4) [2]
Management
• Breastfeeding should be continued and par-
ents reassured
• Ensure there are no other causes of prolonged
Table 2.4 Suggested use of phototherapy and exchange
hyperbilirubinemia (e.g., galactosemia, hypo- transfusion in preterm infants < 35 weeks gestational
thyroidism, urinary tract infection (UTI), ageb
hereditary spherocytosis) Phototherapy Exchange
• If serum bilirubin levels continue to rise or transfusion
> 20 mg/dL, breastfeeding can be discontin- Initiate phototherapy Total serum
ued for 48 h to observe whether a decrease in Gestational age total serum bilirubin a
bilirubin
−1
TSB concentration occurs. Phototherapy may (wk) (mg dl ) (mg dl−1)
< 28 0/7 5–6 11–14
be considered: 28 0/7–29 6/7 6–8 12–14
–– During this time, the mother should con- 30 0/7–31 6/7 8–10 13–16
tinue to express milk to maintain her supply 32 0/7–33 6/7 10–12 15–18
and supplement the infant with formula 34 0/7–34 6/7 12–14 17–19
–– TSB concentrations usually peak between
a
Use the lower range of the listed total serum bilirubin (TSB) levels
for infants at greater risk for bilirubin toxicity (e.g., lower gesta-
12 and 20 mg/dL (205.2 and 342.1 μmol/L) tional age, serum albumin levels < 2.5 g/dL, clinically unstable
and should decrease by 3 mg/dL infants). Recommendations for exchange transfusion apply to
infants who are receiving intensive phototherapy but whose TSB
(51.3 μmol/L) per day. If this decrease levels continue to increase to the levels listed. For all infants, an
occurs, breastfeeding should be restarted exchange transfusion is recommended if the infant shows signs of
acute bilirubin encephalopathy (hypertonia, arching, retrocollis,
–– Phototherapy, if needed, can be adminis- opisthotonus, high-pitched cry)
tered with standard phototherapy units and bFrom Maisels et al. [2], with permission
biliblankets
60 M. Fuloria
Unconjugated Hyperbilirubinemia • Conjugated bilirubin level > 20% of the TSB

if the total is > 5 mg/dL
Causes Causes
• Increased bilirubin production • Biliary atresia
• Deficiency of hepatic uptake • Thyroid abnormalities
• Increased enterohepatic circulation • Galactosemia
• Glucose-6-phosphate dehydrogenase • Alagille syndrome
(G6PD) deficiency; more common in African • Choledochal cyst
American • Viral infections, e.g., cytomegalovirus (CMV),
• Blood group incompatibility human immunodeficiency virus (HIV)
• Structural defects in erythrocytes • Bacterial infections (UTI, syphilis); sepsis
• Impaired conjugation of bilirubin • Idiopathic neonatal hepatitis
• Prolonged parenteral nutrition
Gilbert syndrome
• Autosomal recessive condition in which
UGT1A1 activity decreases mildly in hepato- Kernicterus
cytes, typically resulting in a benign unconju-
gated hyperbilirubinemia Background
• The likelihood of severe hyperbilirubinemia • Kernicterus is brain injury caused by uncon-
is increased if the infant also has G6PD jugated bilirubin deposition in basal ganglia
deficiency and brain stem nuclei
• Bilirubin can cross the blood-brain barrier
Crigler-Najjar syndrome type 1 and enter the brain tissue if it is unconjugated
• Autosomal recessive and unbound to albumin, or if there is damage
• Severe deficiency of UGT1A1 results in to the blood-brain barrier
intense jaundice in the first days of life and • Acute bilirubin toxicity may occur in a term
persists thereafter. Bilirubin encephalopathy infant if there are no signs of hemolysis and the
develops in the first few days or month after TSB concentration is greater than 25 mg/dL
birth • Physicians should be concerned if the TSB
Crigler-Najjar syndrome type 2 concentration is above 20 mg/dL in a term
• Autosomal dominant infant who has hemolysis
• Bilirubin levels are generally < 20 mg/dL
• The incidence of bilirubin encephalopathy is Clinical presentation
low. • Bilirubin-induced neurologic dysfunction
(BIND) is the term applied to the spectrum of
neurologic abnormalities associated with
Conjugated Hyperbilirubinemia (See hyperbilirubinemia, approximately 15% of
Also Chap. 22 Gastroenterology) babies with BIND have no neurologic signs
• Clinical features have been well described
and can be divided into 3 stages:
Background • Phase 1 (first few days of life):
• Conjugated bilirubin concentration greater –– Decreased alertness
than 1 mg/dL when the TSB concentration is –– Hypotonia
< 5 mg/dL (85.6 μmol/L) or –– Poor feeding, poor suck
2 Neonatology 61
• A high index of suspicion of possible BIND A BO and Rh Incompatibility (See

at this stage that leads to prompt intervention Chap. 10 Hematology/Oncology)
can halt the progression of the illness, signifi-
cantly minimizing long-term sequelae • ABO incompatibility may occur if the moth-
–– Of note, seizure is not typically associated er’s blood type is O and the infant’s blood
with acute bilirubin encephalopathy type is A or B
• Phase 2 (variable onset and duration): • Infants should be assessed for jaundice at a
–– Hypertonia of the extensor muscles is a minimum of every 8–12 h after birth; earlier
typical sign. Patients present clinically assessment is indicated if cord bilirubin is
with retrocollis (backward arching of the > 1.5 mg/dL
neck), opisthotonus (backward arching of
the back), or both. Infants who progress to
this phase develop long-term neurologic Transcutaneous Bilirubin Devices
deficits
• Phase 3 (infants aged > 1 wk): Hypotonia is a • Newer devices used to detect transcutaneous
typical sign bilirubin (TcB) have been shown to correlate
well with TSB
–– Important to note that TcB assessments
Chronic Bilirubin Encephalopathy and clinical examination are unreliable
after phototherapy
• Clinical features evolve slowly over the first • Once TcB or TSB has been measured, the
several years of life in the affected infant result should be interpreted based on the
• The clinical features can be divided into nomogram
phases: –– The value should be plotted on the nomo-
–– First phase occurs in the first year of life: gram to assess the risk level and whether or
Hypotonia, hyperreflexia, and delayed not treatment is indicated
acquisition of motor milestones • AAP Subcommittee on Hyperbilirubinemia
–– Tonic neck reflex can be observed has recommended assessing TSB or TcB on
• Extrapyramidal abnormalities: Athetosis is all newborns before discharge [3]
the most common movement disorder,
although chorea can also occur
–– Upper extremities are usually more affected Management of Hyperbilirubinemia
than the lower ones; bulbar functions can
also be impacted Feeding
• Visual abnormalities: • More frequent feeding (breastfeeding or bot-
–– Ocular movements are affected, most com- tle feed) every 2–3 h
monly resulting in upward gaze
–– Horizontal gaze abnormalities Phototherapy
–– Gaze palsies • Phototherapy works by converting bilirubin
• Auditory abnormalities: into a water-soluble compound, lumirubin,
–– High frequency hearing loss which is excreted in the urine or bile
–– Delayed language acquisition • When bilirubin decreases to 13–14 mg/dL,
• Abnormalities of dentition: Dental enamel discontinue phototherapy
hypoplasia • Consider exchange transfusion if the TSB is
• Cognitive function is relatively spared, but not decreasing or is moving closer to the level
minor intellectual deficits can also occur for exchange transfusion
62 M. Fuloria
• Depending on the cause of hyperbilirubine- Treatment

mia, measuring TSB 24 h after discharge to • Treat with 1 mg IV vitamin K ± fresh frozen
check for rebound is an option plaza (FFP)
Complications of phototherapy Prevention

• Insensible water loss (increase fluid intake or • 1 mg vitamin K IM administration after birth
the volume and frequency of feeding)
• Phototherapy may be associated with loose
stool Respiratory Distress Syndrome (RDS)
• Retinal damage (covering the eye is routine (aka Hyaline Membrane Disease)
during phototherapy)
Background
Treatment of hyperbilirubinemia if bilirubin • The most common cause of respiratory fail-
level is not decreasing ure in the newborn
• Intravenous immunoglobulin • Occurs almost exclusively in premature
• Exchange transfusion infants
• The incidence and severity of RDS are related
inversely to the GA of the newborn infant
Hemorrhagic Disease • RDS develops in premature infants because
of the Newborn of impaired surfactant synthesis and secretion
leading to lung atelectasis
Background • RDS does not occur in all preterm babies
• Also referred to as vitamin K deficiency • Surfactant protein (SP) deficiency occurs in a
bleeding small group of term infants with severe respi-
–– Transient deficiency in vitamin ratory distress that leads to intractable respi-
K-dependent factors ratory failure and death
• Presents in three forms: –– SP-B deficiency is the most common form
–– Early (first 24 h): Associated with mater- and occurs as an autosomal recessive trait
nal use of drugs such as anticoagulants,
barbiturates, carbamazepine, phenytoin, Surfactant is stored in type II alveolar cells and
some cephalosporins, rifampin composed of
–– Classic (2–7 days of life): Associated with • Dipalmitoyl phosphatidylcholine
no vitamin K prophylaxis at birth • Phosphatidylglycerol
–– Late (after 1 week of age): Occurs in exclu- • Apoproteins (SP-A, B, C, and D)
sively breastfed infants who have not • Cholesterol
received adequate vitamin K prophylaxis,
and with vitamin K malabsorption, e.g., Risk factors
neonatal hepatitis, biliary atresia • Prematurity
• Maternal DM
Clinical presentation • C-section
• Bleeding can occur anywhere, e.g., GI, nasal, • Asphyxia
subgaleal, intracranial, circumcision bleeding, • Male gender
following cord separation, after phlebotomy • Hypothermia
• Multiple gestations
Diagnosis • Family history of a sibling who developed
• Elevated PT due to low vitamin K RDS
2 Neonatology 63
Factors that decrease the risk of RDS –– Poor lung expansion

• Premature rupture of membranes –– The appearance of GBS pneumonia on
• Maternal hypertension chest radiograph can be identical to that of
• Sub-acute placental rupture RDS
• Maternal use of narcotics • Blood gas
–– Hypoxia
Clinical presentation –– Metabolic acidosis
• Same as that seen in other conditions that –– Hypercarbia
cause respiratory distress • Fetal lung test for maturity prediction
• Tachypnea usually > 60 breaths/min –– Lecithin-to-sphingomyelin ratio and/or
• Expiratory grunting (from partial closure of –– Testing for the presence of phosphatidylg-
glottis) lycerol in amniotic fluid obtained by
• Subcostal and intercostal retractions amniocentesis
• Cyanosis
• Nasal flaring Management
• Extremely premature neonates may develop • Prenatal administration of steroids
apnea and/or hypothermia (betamethasone)
• Maintain core temperature
Diagnosis • Nasal continuous positive airway pressure
• Chest radiograph (Fig. 2.6) (CPAP) is often used for initial stabilization
–– Bilateral, diffuse, reticular granular, or in spontaneously breathing premature infants
ground glass appearance immediately after birth
–– Diffuse atelectasis and air bronchograms • Intubation and mechanical ventilation (MV)
(prominent air bronchograms represent in infants who do not respond to noninva-
aerated bronchioles superimposed on a sive ventilation strategies and surfactant
background of collapsed alveoli) therapy
• Surfactant prophylaxis may be considered in
infants < 27 weeks gestation
• Prophylactic surfactant may be considered
for neonates > 26 weeks but < 30 weeks ges-
tation if intubation is required or if the mother
has not received any prenatal steroids
• Many institutions practice only rescue
surfactant
• When possible, duration of MV should be
shortened by early extubation to CPAP after
surfactant administration, provided the new-
born is otherwise stable
• IV fluids if respiratory status is not stable:
10% glucose in the first 24 h
Fig. 2.6 Chest radiograph of premature newborn shows a • Parenteral nutrition should be provided to
bilateral and symmetrical diffuse ground glass lung appear- very preterm infants
ance with a hyperinflated thorax (due to intubation). Without • Treat with antibiotics until sepsis is ruled out
intubation, the thorax typically has a low volume. In some • Cardiac causes should be considered in wors-
patients, air-bronchograms can be seen. The patient has
venous and arterial umbilical catheters
ening cases despite appropriate therapy
64 M. Fuloria
Prenatal steroids –– Prominent perihilar vascular markings,

• Decreases the incidence and severity of RDS which correlates with the engorgement of the
• Usually given to women at 24–34 weeks ges- lymphatic system with retained lung fluid
tation with high risk for preterm birth, e.g., –– Fluid in the fissures
premature rupture of membrane –– Small pleural effusions may also be
present
ransient Tachypnea of the Newborn

T Treatment
(TTN) • Supportive care
• Supplemental oxygen may be required
Background • Antibiotics may be considered until sepsis
• TTN is a common, relatively benign self-lim- has been ruled out
ited disease in newborns • Provide IV hydration and nutrition
• Infants with TTN present within the first few
hours of life with tachypnea, increased oxy-
gen requirement, and arterial blood gases Persistent Pulmonary Hypertension
(ABGs) that do not reflect carbon dioxide of the Newborn (PPHN)
retention
• TTN is the result of a delay in clearance of Background
fetal lung fluid by the lymphatics and pulmo- • PPHN is defined as the failure of the normal
nary circulation, with resultant transient pul- circulatory transition that occurs after birth
monary edema –– Syndrome characterized by marked pul-
• Most common in infants delivered between monary hypertension that causes hypox-
37 and 42 weeks gestation emia secondary to right-to-left shunting of
• Common with C-section delivery in the blood at the foramen ovale and ductus
absence of labor arteriosus
• Other risk factors are male sex; perinatal • Most often recognized in term or near-term
asphyxia; umbilical cord prolapse; and mater- neonates but can also occur in preterm infants
nal complications such as asthma, diabetes, • Selective serotonin reuptake inhibitors
and anesthesia and analgesia during labor (SSRIs), commonly prescribed antidepres-
sants, have been reported to be associated
Clinical presentation with PPHN, especially during the third tri-
• Signs of respiratory distress (e.g., tachypnea, mester of pregnancy
nasal flaring, grunting, retractions, cyanosis • Genetic factors may increase susceptibility to
in extreme cases) become evident shortly pulmonary hypertension, e.g., polymor-
after birth phisms of the carbamoyl phosphate synthase
• The disorder is transient with resolution usu- gene and urea cycle enzyme genes
ally occurring within 72 h after birth • Higher frequency in babies with Down
• Extreme cases may exhibit cyanosis syndrome
• Prolonged course > 72 h or clinical deteriora-
tion may suggest other diagnosis Etiology and common associated conditions
• Idiopathic
Diagnosis • RDS
• Chest radiograph: • Polycythemia
–– Hyperinflation • Hypoglycemia
2 Neonatology 65
• Meconium aspiration • Minimize stimulation

• GBS pneumonia • Maintain a normal body temperature and cor-
• Sepsis rect electrolytes, glucose abnormalities and
• Diaphragmatic hernia metabolic acidosis
• Pulmonary hypoplasia • Maintain adequate systemic BP
• IDM • MV; avoid hyperventilation
• Down syndrome • Inhaled nitric oxide
• Extracorporeal membrane oxygenation
Clinical presentation (ECMO)
• Usually symptoms appear in the first 24 h
• Tachypnea
• Cyanosis econium Aspiration Syndrome
M
• Respiratory distress (grunting, flaring, retrac- (MAS)
tion, tachycardia)
• Profound and often labile hypoxemia Background
• Preductal and postductal oxygen saturation • Meconium aspiration is one of the most com-
gradient difference of at least 10% (with pre- mon etiologies of respiratory failure in
ductal saturations being higher) newborns
• Loud, single second heart sound (S2) • Because meconium is rarely found in the
• A harsh systolic murmur secondary to tricus- amniotic fluid prior to 34 weeks gestation,
pid regurgitation may be heard meconium aspiration primarily affects infants
• Systemic hypotension, shock, and evidence born at term and post-term
of poor perfusion may occur
Factors that increase the risk of meconium
Diagnosis aspiration
• Hypoxemia is universal and poorly respon- • Placental insufficiency
sive to 100% oxygen • Maternal hypertension
• Differential cyanosis: Higher oxygen satura- • Preeclampsia
tion in preductal blood (right radial artery) • Oligohydramnios
than that obtained from tibial arteries • Maternal drug abuse, especially of tobacco
(postductal) and cocaine
• Echocardiography is essential for distinguish- • Maternal infection/chorioamnionitis
ing congenital heart disease from PPHN, • Fetal hypoxia and acidosis
which is a diagnosis of exclusion
–– Right ventricular hypertrophy Clinical presentation
–– Bowing of the interventricular septum into • Cyanosis
the left ventricle • Nasal flaring
–– Tricuspid regurgitation • End-expiratory grunting
–– Right-to-left or bidirectional shunting at • Intercostal retractions
the patent foramen ovale and/or patent • Tachypnea
ductus arteriosus • Barrel chest in the presence of air trapping
• Auscultated rales and rhonchi (in some
Management cases)
• Treatment of the underlying cause is the most • Yellow-green staining of fingernails, umbili-
important step cal cord, and skin may be observed
66 M. Fuloria
Diagnosis neumothorax
P
• Chest radiograph and Pneumomediastinum
–– Air trapping and hyperexpansion from air-
way obstruction Background
–– Diffuse chemical pneumonitis (streaky, • Pneumothorax refers to the presence of air or
linear, or patchy infiltrates) gas in the pleural cavity between the visceral
–– Acute atelectasis and parietal pleura
–– Pneumomediastinum and other air leak • Pneumomediastinum is air in the mediasti-
syndromes num that may be confused with
pneumothorax
Prevention of MAS • Pneumothorax may be iatrogenic or
• AAP recommendations spontaneous
–– If the infant is not vigorous (defined as • Factors associated with pneumothorax:
depressed respiratory effort, poor muscle –– Overly vigorous resuscitation at birth
tone, and/or heart rate < 100 beats/min): –– RDS
Place the infant on a radiant warmer, clear –– MAS
the secretions with a bulb syringe, and pro- –– Pneumonia
ceed with the normal steps of newborn –– Pulmonary hypoplasia
resuscitation (i.e., warming, repositioning –– Assisted ventilation
the head, drying, and stimulating). If after
these initial steps the infant is still apneic Clinical presentation
or the heart rate is < 100 beats bpm, admin- • Depends on the severity and size of the
ister PPV to minimize the delay in initiat- pneumothorax
ing ventilation • Tension pneumothorax:
–– If the infant is vigorous (defined as normal –– Cyanosis
respiratory effort, normal muscle tone, and –– Hypoxemia
heart rate > 100 beats/min): Do not elec- –– Tachypnea
tively intubate. Clear secretions and meco- –– Sudden decrease in heart rate
nium from the mouth and nose with a bulb –– Hypotension
syringe and proceed with the normal steps –– Narrowed pulse pressure
of neonatal resuscitation –– Decreased breath sounds on the affected
–– Resuscitation should follow the same prin- side
ciples as for infants born through clear –– Shift of the maximal cardiac impulse away
amniotic fluid from the affected side
Management Chest radiograph

• Oxygen therapy • Shift of mediastinum away from the side of
• Surfactant therapy commonly used pneumothorax
• Noninvasive or invasive MV • Depressed diaphragm
• Supportive care—Maintain fluid and electro- • Displacement of the lung to the opposite side
lyte balance; maintain normal BP
• Inhaled nitric oxide Management
• ECMO if infant unresponsive to medical • Symptomatic tension pneumothorax is an
management emergency
2 Neonatology 67
–– Transillumination of the chest is useful for • The microorganisms most commonly associ-
immediate diagnosis ated with late onset infection include the
–– Limited time for chest radiograph following:
confirmation –– Coagulase-negative Staphylococcus
• If the patient is deteriorating rapidly: –– S. aureus
–– A 22–24-gauge needle or angiocath can be –– E. coli, Klebsiella, enterococci,
inserted for aspiration (thoracentesis). The Pseudomonas, Serratia
site of puncture should be at the second or –– Candida
third intercostal space along the midcla- –– GBS
vicular line
–– Thoracostomy or chest tube placement Risk factors
may be needed • Maternal GBS status
• Asymptomatic pneumothorax: 100% oxygen • Premature ROM
administration for 8–12 h may be considered. The • Prolonged ROM
rate of resolution of spontaneous pneumothora- • Maternal fever
ces is not improved with oxygen supplementa- • Maternal UTI
tion. Because of concerns regarding the risks of • Prematurity
hyperoxia, we do not routinely administer sup- • Chorioamnionitis
plemental oxygen above the concentration • Low BW
needed to maintain adequate saturation. • Male gender
• Intrapartum or postpartum instrumentation
Neonatal Sepsis Initial clinical presentations of infection

• In newborns, signs of infection are nonspe-
Background cific and can be subtle or dramatic (Table 2.5)
• Neonatal sepsis may be categorized as early
onset or late onset Common clinical manifestation of bacterial
• Newborns with early onset sepsis (< 72 h): sepsis
85% present within 24 h, 5% present at 24–48 h, • Pneumonia
and a smaller percentage present within 48–72 h. • Meningitis
Onset is most rapid in premature neonates • Bacteremia
• Late onset sepsis occurs at > 72 h–28 days of • Osteomyelitis
life and is acquired from the caregiving • UTIs
environment
Investigations
• The microorganisms most commonly associ-
• Cultures (blood, urine, cerebrospinal fluid)
ated with early onset infection include the
• CBC and differential (normal count does not
following:
rule out sepsis)
–– GBS
–– Neutropenia, especially an absolute neu-
–– Escherichia coli
trophil count < 1800 cells/mcL
–– Coagulase-negative Staphylococcus
–– Immature-to-total (I/T) neutrophil ratio
–– Staphylococcus aureus
> 0.15 in the first 24 h of life is suggestive
–– Haemophilus influenzae
of sepsis
–– Listeria monocytogenes
–– Thrombocytopenia
–– Enterococci
• C-reactive protein (CRP)
–– Haemophili and other Gram-negatives
• Procalcitonin
(Klebsiella, Enterobacter, Citrobacter,
• Coagulation studies
Acinetobacter, Pseudomonas)
68 M. Fuloria
Table 2.5 Initial clinical presentations of infection in new- • Begin antibiotics as soon as diagnostic tests
born infants are performed
Possible clinical presentation of –– Early onset sepsis: Ampicillin and
System neonatal sepsis gentamicin
General Temperature instability
• An infant with temperature instability needs
Hypoglycemia
Poor feeding thermoregulatory support with a radiant
Respiratory Apnea warmer or incubator
Tachypnea, nasal flaring, grunting,
retractions Medications
Cyanosis • The antibiotics commonly used to treat neo-
Cardiovascular Pallor, mottling, cold, clammy skin
Tachycardia, bradycardia,
natal sepsis include:
hypotension –– Ampicillin and gentamicin for early onset
Delayed capillary refill sepsis
Gastrointestinal Vomiting (bilious or nonbilious) –– Nafcillin/vancomycin and gentamicin/ceph-
Abdominal distension alosporins for late onset sepsis (antibiotic
Central nervous Seizures
system Tremor coverage should be directed at organisms
Abnormal reflexes implicated in hospital-acquired infections)
Irregular respiration • The choice of antibiotic agents should be
Full fontanel based on the specific organisms associated
High-pitched cry
with sepsis
Hematologic Pallor, jaundice
system Thrombocytopenia, bleeding,
petechiae, purpura
Renal Oliguria roup B Streptococcal Infection
G
Others Leukocytosis or leukopenia in Neonates
Elevated immature WBCs, e.g., bands
Elevated C-reactive protein
DIC
Background
Lactic acidosis • GBS, also known as Streptococcus agalac-
Hypoxemia tiae, is best known as a cause of postpartum
WBCs white blood cells, DIC disseminated intravascular coagulation infection and as the most common cause of
neonatal sepsis
• Lumbar puncture is warranted for early- and • Neonates can acquire the organism vertically
late onset sepsis in utero or from the maternal genital tract
• HSV PCR testing in suspected cases during delivery
• Chest radiograph –– Although the transmission rate from moth-
• MRI may be needed late in the course of ers colonized with S. agalactiae to neo-
complex neonatal meningitis to document nates delivered vaginally is approximately
obstructive hydrocephalus 50%, only 1–2% of colonized neonates go
• Head ultrasonography in neonates with men- on to develop invasive GBS disease
ingitis may reveal evidence of ventriculitis, • Preterm neonates have higher rates of GBS
abnormal parenchymal echogenicity, extra- late onset disease
cellular fluid, and chronic changes • Early onset GBS sepsis often presents within
• Serially, head ultrasonography can reveal the 24 h of delivery but can become apparent up
progression of complications to 7 days postpartum
• Late onset GBS sepsis is defined as infection
Management that presents between 1 week postpartum and
• When neonatal sepsis is suspected, treatment age 3 months
should be initiated immediately because of
the neonate’s relative immunosuppression
2 Neonatology 69
• Optimal timing of maternal GBS screening is • If the mother received IAP > 4 h before deliv-
between 35 and 37 weeks gestation ery and the infant is > 37 weeks and asymp-
• Adequate treatment of maternal GBS infec- tomatic, provide routine clinical care
tion does not rule out GBS infection in infants
Clinical presentation
Indication of intrapartum GBS prophylaxis • Early onset GBS infection manifests with
• Previous infant with invasive GBS disease bacteremia, sepsis, pneumonia, and
• GBS bacteriuria during any trimester of the meningitis
current pregnancy –– Most infants present early in the first
• Positive GBS vaginal-rectal screening culture 8–12 h
in late gestation during current pregnancy –– Respiratory distress (tachypnea, grunting,
–– Intrapartum antibiotic prophylaxis is not and retractions)
indicated in the two above circumstances if –– Cyanosis, apnea, poor perfusion, hypoten-
a cesarean delivery is performed before sion, and signs of sepsis can rapidly develop
onset of labor on a woman with intact –– Shock
amniotic membranes –– Death can occur
• Unknown GBS status at the onset of labor • Late onset GBS infection presents as:
(culture is not done, incomplete, or results –– Meningitis
unknown) and any of the following: –– Occult bacteremia
–– Delivery at < 37 weeks gestation –– Focal infections such as osteomyelitis or
–– Amniotic membrane rupture ≥ 18 h arthritis, facial cellulitis, submandibular cel-
–– Intrapartum temperature ≥ 100.4 °F lulitis, or cellulitis-adenitis in other regions
(≥ 38.0 °C)
–– Intrapartum nucleic acid amplification test Diagnosis
(NAAT) positive for GBS • Leukopenia or leukocytosis
• Bandemia
Secondary prevention of early onset GBS dis- • Thrombocytopenia
ease among newborns • Abnormal PT and PTT
• If no GBS prophylaxis was needed, the infant • Chest radiograph may show signs of
should be managed with routine newborn pneumonia
care • Abnormal CSF studies in cases of meningitis
• Full diagnostic evaluation and antibiotic ther- (See also Chap. 9 Infectious Diseases)
apy if any signs of neonatal sepsis at any time
• Blood culture, CBC with differential at birth Treatment
(limited evaluation), and antibiotic therapy if • Ampicillin and gentamicin are used empiri-
chorioamnionitis cally for treatment of GBS disease and substi-
• If intrapartum antibiotic prophylaxis (IAP) tuted with penicillin once the organism is
was not given ≥ 4 h before delivery and infant cultured from a sterile site
< 37 weeks gestation, or duration of rupture • Pneumonia and septicemia usually require
of membrane is ≥ 18 h, do a limited evalua- treatment for 10–14 days
tion and observe for at least 48 h or more in • Meningitis usually treated for 14–21 days
the hospital
• If IAP was not given ≥ 4 h before delivery, Prevention guidelines
infant > 37 weeks gestation and duration of • The drug of choice for intrapartum prophy-
rupture of membrane < 18 h, observe for at laxis remains intravenous penicillin, with
least 48 h or more in the hospital ampicillin as an acceptable alternative.
70 M. Fuloria
• Both agents are given every 4 h until delivery,

with at least one dose administered 4 h before
birth.
• Well-appearing infants whose mothers
received adequate intrapartum prophylaxis
should be observed for at least 48 h. No diag-
nostic testing required.
• Well-appearing infants > 37 weeks gestation
and none/inadequate maternal prophylaxis
with rupture of m embranes < 18 h before
delivery should be observed for 48 h. No
diagnostic testing required.
• Well-appearing infants with none/inadequate
maternal prophylaxis and either < 37 weeks
gestation or rupture of membranes > 18 h
before delivery should have limited evaluation
(blood culture, CBC with diff and platelets at
birth or 6–12 h) and be observed for 48 h.
Fig. 2.7 Chorioretinal scar of the right eye, due to toxoplas-
mosis. (Courtesy of Violeta Radenovich MD MPH,
Children’s Eye Center, Department of Ophthalmology, Texas
Congenital Toxoplasmosis Tech University, El Paso, Texas)
Background • Thrombocytopenia
• Risk of transmission exists with primary • Prematurity
infection but not if the infection is acquired • Cytopenias
before conception • Jaundice
• Infection in the first trimester is less frequent • Maculopapular rash
but results in more severe disease, including • Visual and learning disabilities
fetal death in utero or severe CNS involve-
ment, such as cerebral calcifications and Important
hydrocephalus • Approximately, 75% of congenitally infected
• Infection in the third trimester is more fre- infants are asymptomatic at birth, but up to
quent, and the infant appears normal at birth, 85% of children will develop visual and learn-
but the symptoms may appear later in life, ing disabilities later in life if they are not
e.g., chorioretinitis treated in infancy
• Treatment during pregnancy has been shown
to reduce the rate of transmission and seems Treatment
to reduce serious neurological sequelae • Pyrimethamine and sulfadiazine for 1 year
• Classic triad Congenital Syphilis
–– Chorioretinitis (Fig. 2.7)
–– Hydrocephalus Background
–– Intracranial calcifications • Congenital syphilis is more likely to occur
• Hydrops fetalis and death with maternal primary or secondary syphilis,
• IUGR if maternal disease is of unknown duration or
2 Neonatology 71
untreated, if < 4 weeks have elapsed between Treponema-specific tests

treatment and delivery, or if maternal plasma • Treponema pallidum immobilization, fluores-
nontreponemal titer (VDRL or RPR) is > 1:16 cent treponemal antibody absorption (FTA-
after therapy or delivery ABS), and T. pallidum particle agglutination
–– The transmission rate approaches 90% if (TPPA) are used to confirm a positive non-
the mother has untreated primary or sec- treponemal serology screening test
ondary syphilis • These test findings become positive soon
• Fetal infection can develop at any time during after infection and typically remain positive
gestation for life, despite adequate treatment
• These test results do not correlate with dis-
Clinical presentation ease activity and are not quantified
• Asymptomatic: 60% of infants born with
congenital syphilis are asymptomatic at birth Management
• Hepatomegaly: The most common physical • Treat congenital infection, either proven or
finding, reported in almost 100%, usually presumed, with 10–14 days of aqueous
with abnormal liver function crystalline penicillin G or penicillin G
• Signs of congenital syphilis are nonspecific procaine
and include: • Aqueous crystalline penicillin G is recom-
–– Prematurity and low BW mended if congenital syphilis is proved or is
–– Hepatomegaly with or without splenomegaly highly suspected
–– Hutchinson teeth, skeletal abnormalities, • Base dosage on chronological, not gesta-
e.g., periostitis or osteitis tional, age
–– Generalized lymphadenopathy • The recommended dosage of aqueous crys-
–– Maculopapular rash—also vesicular rash talline penicillin G is 50,000 U/kg IV every
and bullae—may develop. These lesions 12 h (1 week or younger), then every 8 h for
are highly contagious infants older than 1 week for a total of 10 days
–– Rhinitis (“snuffles”). Nasal secretions are of therapy
highly contagious • The dose for penicillin G procaine is
–– Thrombocytopenia 50,000 U/kg IM as a single daily dose for
–– Coombs negative hemolytic anemia with 10 days
hydrops
• Abnormal CSF examination is seen in half of
symptomatic infants but can also be found in Infection is suspected with the following:
10% of those who are asymptomatic • Physical or radiographic evidence of active
disease
Diagnosis • Serum quantitative nontreponemal titer at
• Nontreponemal serology screening tests: least four times greater than the maternal
RPR and VDRL are the best screening tools titer
• A fourfold or greater rise in titer in the infant • Reactive CSF VDRL test result or abnormal
compared to the mother signifies probable CSF cell count and/or protein levels
active disease • Positive IgM FTA-ABS test findings
• Fourfold increase in titer following therapy • Positive dark-field microscopy findings or
suggests reinfection or relapse and necessi- positive findings when staining for trepo-
tates reevaluation nemes in placenta or umbilical cord
72 M. Fuloria
ailure to Pass Meconium in the First

F Management
48 h of Life • Plain radiograph for any newborn who did
not pass stool within the first 48 h of life
Background • Hyperosmolar Gastrografin enemas are con-
• 97% of term infants and 76% of premature sidered the initial diagnostic procedure and
infants pass a stool in the first 24 h of life are often therapeutic in patients with meco-
• Almost every infant will have passed meconium plug syndrome
nium by 36 h (99.8%) of age. 99% of prema- • Rectal biopsy should be considered in all
ture infants pass a stool by 48 h these infants because of the high risk of
Hirschsprung disease (up to 38%)
Differential diagnosis
• Constipation
• Anorectal anomalies (imperforate anus) Meconium Ileus
• Meconium plug
• Meconium ileus Background
• Hirschsprung disease • Meconium ileus represents obstruction of the
• Ileal atresia small bowel caused by accumulation of sticky
• Incarcerated hernia and inspissated intraluminal meconium
• Malrotation • The third most common cause of neonatal
small bowel obstruction
• Accounts for about 30% of cases of intestinal
Meconium Plug Syndrome obstruction in newborns
• Meconium ileus occurs in 10–20% of patients
Background with CF
• A transient form of distal colonic or rectal –– In most cases, this results from intestinal
obstruction suspected to be related to tran- and pancreatic dysfunction associated with
sient decrease in intestinal motility CF
• Meconium plug syndrome is the most com- –– However, not all patients with meconium
mon form of functional distal obstruction in ileus have CF
newborns
• More common in infants of diabetic mothers Clinical presentation
• Usually occurs in the lower colon or anorec- • Abdominal distention, delayed passage of
tal region meconium, and bilious emesis
• Sometimes the impacted meconium can be
Common associated conditions palpated
• Small left colon syndrome • Massive distention, abdominal tenderness, or
• Magnesium sulfate therapy for preeclampsia abdominal erythema indicates the presence of
• Maternal drug abuse complications such as volvulus, intestinal
• CF necrosis, perforation, and meconium
• Hypothyroidism peritonitis
• Hirschsprung disease
Diagnosis
Clinical presentation • Abdominal radiographs: May reveal signs of
• Failure to pass meconium in the first 24–48 h either small or large bowel obstruction (dis-
• Relieved by passage of meconium plugs tended bowel, few air-fluid levels, and in the
2 Neonatology 73
right lower abdomen), meconium mixed with • Abdominal distention, abdominal tenderness,
air “soap bubble,” which has a ground-glass or both
appearance on plain film • Ileus/decreased bowel sounds
• The presence of calcifications, free air, or very • Abdominal wall erythema (advanced stages)
large air-fluid levels suggests complications • Hematochezia
• The small bowel is of narrow caliber below • Apnea, bradycardia
the plug and dilated above the plug • Labile body temperature
• Sweat test or genetic testing for all infants with • Lethargy
meconium ileus because of high risk of CF • Decreased peripheral perfusion
• Shock (in advanced stages)
Management • Cardiovascular collapse
• Simple meconium ileus may be successfully • Bleeding diathesis (consumption coagulopathy)
treated by administration of a diatrizoate
meglumine (Gastrografin) enema and IV flu- Diagnosis
ids; the success rate is 16–50% • Abdominal radiograph
• If the Gastrografin enema is unsuccessful, –– The mainstay of diagnostic imaging is
operative evacuation of the obstructing meco- abdominal radiography; radiographic appear-
nium by irrigation will be necessary ance of NEC depends on severity
• Complications such as atresia, perforation, –– Abnormal gas pattern
and meconium peritonitis always require –– Dilated loops
immediate surgery, including resection, intes- –– Thickened bowel walls (suggesting edema/
tinal anastomosis, and ileostomy inflammation)
–– Pneumatosis intestinalis (intramural air
bubbles) is a radiologic sign pathogno-
Necrotizing Enterocolitis (NEC) monic of NEC
–– Abdominal free air is ominous and usually
Background requires emergency surgical intervention
• NEC is the most common GI medical/surgi- –– Portal gas represents air present in the por-
cal emergency occurring in preterm neonates tal venous system. Its presence is consid-
• Acute inflammatory disease with variable ered to be a poor prognostic sign
damage to the intestinal tract, ranging from
mucosal injury to full-thickness necrosis and Laboratory studies
perforation • Hyponatremia
• NEC affects close to 10% of infants who • Metabolic acidosis
weigh less than 1500 g, with mortality rates • Thrombocytopenia
of 50% or more, depending on severity • Leukopenia or leukocytosis with left shift
• It can also be observed in term and near-term • Neutropenia
babies • Prolonged PT and activated PTT (aPTT),
• The main cause of NEC is still unclear, but decreasing fibrinogen, rising fibrin split prod-
the risk is higher in premature infants ucts (in cases of consumption coagulopathy)
Clinical presentation Management

• Feeding intolerance • Nothing by mouth and IV fluids
• Delayed gastric emptying, high gastric • Rapid nasogastric decompression
residuals • Start IV antibiotics after cultures are taken:
74 M. Fuloria
–– Frequently used regimen is ampicillin, Clinical presentation

aminoglycoside (e.g., gentamicin) or third- • Respiratory distress, tachypnea, grunting,
generation cephalosporin (cefotaxime), retraction, and cyanosis
piperacillin and tazobactam, and clindamy- –– Respiratory distress and cyanosis in the
cin or metronidazole first minutes or hours of life, although a
–– Vancomycin should be included if later presentation is possible
Staphylococcus coverage is deemed –– The respiratory distress can be severe and
appropriate may be associated with circulatory insuffi-
–– Medical management usually continues for ciency, requiring aggressive resuscitative
10–14 days with parenteral nutrition pro- measures
vided during that time • Scaphoid abdomen
• Consult with a pediatric surgeon at the earli- • Increased chest wall diameter
est suspicion of developing NEC • Heart sounds may be shifted to the right in
patients with left-sided CDH
Indication for surgery • Bowel sounds may be heard in the chest with
• Intestinal perforation with free air in the peri- a decrease in breath sounds bilaterally
toneal space • Associated anomalies: Dysmorphisms such as
• Peritoneal tap showing feces or pus craniofacial abnormalities, extremity abnor-
• Deteriorating clinical condition despite medi- malities, or spinal dysraphism may suggest
cal treatment syndromic congenital diaphragmatic hernia
• Compartment syndrome
Laboratory tests
Note: Patients who are extremely small and ill • ABG measurements to assess for pH, PCO2,
may not have the stability to tolerate laparotomy. and PaO2
If free air develops in such a patient, one may con- • Chromosome studies, including microarray
sider inserting a peritoneal drain under local anes- analysis, if associated anomalies
thesia in the NICU. • Levels of serum electrolytes, ionized calcium,
and glucose
• Continuous pulse oximetry is valuable in the
Congenital Diaphragmatic diagnosis and management of PPHN
Hernia (CDH)
Imaging studies
Background • Chest radiography to confirm diagnosis of
• Herniation of abdominal viscera into the tho- CDH and to rule out pneumothorax
racic cavity through a defect in the diaphragm • Cardiac and renal ultrasonography to rule out
• There is a variable degree of pulmonary associated anomalies
hypoplasia associated with a decrease in • Cranial sonography when an infant is consid-
cross-sectional area of the pulmonary vascu- ered for ECMO
lature and alterations of the surfactant –– Prognosis is worse if ECMO is required
system
• Approximately 85% are left-sided Delivery room management
• Approximately 50–60% are diagnosed • Avoiding mask ventilation and immediately
antenatally intubating the trachea
2 Neonatology 75
• Endotracheal intubation and MV: Required in • During cerebral hypoxia-ischemia, the uptake
infants with severe CDH who present in the of glutamate, which is the major excitatory
first hours of life neurotransmitter of the mammalian brain is
impaired
Management • Accumulation of Na+ coupled with the failure
• Placement of a sump/Replogle tube and con- of energy-dependent enzymes such as Na+/
necting it to continuous suction to prevent K+-ATPase leads to rapid cytotoxic edema
bowel distention and further lung and necrotic cell death
compression
• Avoiding high peak inspiratory pressures Diagnosis
with MV; synchronizing ventilation with the • Profound metabolic or mixed acidemia
infant’s respiratory effort (pH < 7) in an umbilical artery blood sample,
• Continuous monitoring of oxygenation, BP, if it was obtained
and perfusion • Persistence of an Apgar score of 0–3 for lon-
• Maintaining glucose and ionized calcium ger than 5 min
concentrations within reference range • Neonatal neurologic sequelae (e.g., seizures,
• Vasoactive agents (e.g., dopamine, dobuta- coma, hypotonia)
mine, milrinone) as needed • Multiple organ involvement (e.g., kidney,
• Echocardiogram is a critically important lungs, liver, heart, intestines)
imaging study, and it guides therapeutic deci-
sion by measuring pulmonary and systemic Clinical presentation
artery pressure • Mild hypoxic-ischemic encephalopathy
• Surgical correction –– Muscle tone may be slightly increased, and
deep tendon reflexes may be brisk during
the first few days
Hypoxic Ischemic Encephalopathy – – Poor feeding, irritability, excessive crying
(HIE) or sleepiness may be observed
–– The neurologic examination findings nor-
Background malize by 3–4 days of life
• Perinatal asphyxia, more appropriately • Moderately severe hypoxic-ischemic
known as hypoxic-ischemic encephalopathy encephalopathy
(HIE), is characterized by clinical and labora- –– The infant is lethargic, with significant
tory evidence of acute or subacute brain hypotonia and diminished deep tendon
injury due to asphyxia reflexes
• Birth asphyxia causes 23% of all neonatal –– The grasp, Moro, and suck reflexes may be
deaths worldwide sluggish or absent
–– The infant may experience occasional peri-
Pathogenesis ods of apnea
• Brain hypoxia and ischemia due to systemic –– Seizures may occur within the first 24 h of
hypoxemia, reduced cerebral blood flow, or life
both are the primary physiological processes –– Full recovery within 1–2 weeks is possible
that lead to hypoxic-ischemic encephalopathy and is associated with a better long-term
• Excitatory amino acid (EAA) receptor over- outcome
activation plays a critical role in the patho- • Severe hypoxic-ischemic encephalopathy
genesis of neonatal hypoxia-ischemia –– Stupor or coma is typical. The infant may
not respond to any physical stimulus
76 M. Fuloria
–– Breathing may be irregular, and the infant I ntraventricular Hemorrhage (IVH)

often requires ventilatory support and Leukomalacia
–– Generalized hypotonia and depressed deep
tendon reflexes are common Background
–– Neonatal reflexes (e.g., sucking, swallow- • A predominant disorder of preterm infants
ing, grasping, Moro) are absent • Originates in the periventricular subependy-
–– Skewed deviation of the eyes, nystagmus, mal germinal matrix with subsequent entrance
bobbing, and loss of “doll’s eye” (i.e., con- of blood into the ventricular system
jugate) movements
–– Pupils may be dilated, fixed, or poorly Risk factors
reactive to light • Extreme prematurity
–– Seizures • Hypoxic-ischemic insult
–– Irregularities of heart rate and BP are com- • Coagulopathy
mon during the period of reperfusion • Respiratory disturbances—hypercarbia,
injury hypocarbia, pneumothorax, hypoxemia, rapid
–– Death from cardiorespiratory failure alterations in blood gases
• Rapid volume expansion
Laboratory studies • Sudden elevation of arterial BP
• Serum electrolyte levels, renal, liver, and car-
diac function study Classification of IVH
• Coagulation system—includes PT, PTT, and • Grade I: Hemorrhage is confined to the ger-
fibrinogen levels minal matrix
• ABG—Blood gas monitoring is used to • Grade II: IVH without ventricular dilatation
assess acid base status and to avoid hyperoxia • Grade III: IVH with ventricular dilatation
and hypoxia, as well as hypercapnia and • Grade IV: Intraparenchymal hemorrhage
hypocapnia
Imaging studies • Sudden drop in hematocrit level
• Head imaging study, e.g., MRI of the brain or • Apnea
cranial ultrasonography • Bradycardia
• Electrocardiogram (ECG) • Acidosis
• Electroencephalogram (EEG) • Seizures
• Hearing test • Change in muscle tone
• Retinal and ophthalmic examination • Catastrophic syndrome (rapid onset stupor,
coma, respiratory abnormalities, seizures,
Management decerebrate posturing, fixed pupil to light,
• Fluid and ventilation management flaccid quadriparesis)
• Treatment of seizures
• Hypothermia therapy (selective brain cooling Diagnosis
or total body hypothermia) • Ultrasonography is the study of choice
–– Extensive experimental data suggest that • All infants younger than 30 weeks gestation
mild hypothermia (3°–4°C below baseline should be screened by cranial ultrasonogra-
temperature) applied no later than 6 h fol- phy at 7–14 days postnatal life and at
lowing injury is neuroprotective 36–40 weeks postmenstrual age. Instead of a
2 Neonatology 77
cranial ultrasound, some institutions prefer to Table 2.6 Teratogens

obtain a brain MRI at term corrected age Drug name Effect on fetus
• Serial ultrasonography is indicated weekly Phenytoin Broad, low nasal bridge
to follow for progression of hemorrhage and Midface hypoplasia and epicanthal fold
Distal digital or nail hypoplasia
the development of post-hemorrhagic Wide spaced eyes (hypertelorism)
hydrocephalus Intellectual disability
IUGR
Complication Cardiovascular abnormalities
• Obstructive hydrocephalus Bleeding (vitamin K deficiency)
• Nonobstructive hydrocephalus Valproic acid Neural tube defect (spina bifida)
Cardiac, renal, and limb anomalies
• Developmental impairment Carbamazepine Orofacial clefts
• Cerebral palsy (CBZ)
• Seizures Warfarin Bone stippling
Facial anomalies
Prognosis Fetal bleeding and death
Lithium Ebstein anomalies
• Grade I and grade II hemorrhage:
Hypothyroidism
Neurodevelopmental prognosis is excellent Nephrogenic diabetes insipidus
• Grade IV (severe with either periventricular Macrosomia
hemorrhagic (PVH) infarction and/or peri- Cocaine Limb defect or reduction
ventricular leukomalacia): Mortality Intracranial hemorrhage
Leukomalacia
approaches 80%. A 90% incidence of severe
Nonduodenal intestinal atresia
neurological sequelae including cognitive Gastroschisis (most likely due to
and motor disturbances disruption of omphalomesenteric artery)
Marijuana No specific feature to identify because
Prevention of possible poly-drug abuse
• Use of antenatal steroids Irritability
Tremulousness
• Avoid hypoxia-ischemia Abnormal response to visual stimuli
• Avoid large and rapid fluctuation of BP Cigarette Low birth weight for gestational age
• Avoid rapid infusion of volume expanders smoking
• Correct acid base abnormalities Danazol Virilization
• Correct coagulation abnormalities Tetracycline Retarded skeletal growth, pigmentation
of teeth, hypoplasia of enamel, cataract,
• Gentle handling of preterm babies limb malformations
Teratogens (Table 2.6) Clinical presentation

• Small for GA
• Short palpebral fissures (< 10% for age)
Fetal Alcohol Syndrome • Epicanthal folds
• Micrognathia
Background • Midface hypoplasia
• Adverse fetal, neonatal, and pediatric effects • Microphthalmia
occur with maternal alcohol consumption • Smooth philtrum
during pregnancy • Thin upper lip
• The greater the intake of alcohol, the more • Microcephaly
severe the signs • Irritability in infancy
• No safe amount of alcohol during pregnancy • Intellectual impairment (mild to moderate
has yet been determined intellectual disability)
78 M. Fuloria
• Cognitive impairment resuscitation skills, including endotracheal

• Hyperactivity in childhood or attention-defi- intubation.
cit/hyperactivity disorder (ADHD) • The most common form of esophageal atresia
• Skeletal abnormalities, e.g., radioulnar and tracheo-esophageal fistula is esophageal
synostosis atresia with a distal fistula (88% of cases),
• Hearing and visual abnormalities, e.g., deaf- where the upper esophagus ends in a blind
ness and strabismus pouch and the trachea is connected by a fis-
tula to the distal esophagus.
• Approximately 85% of congenital diaphrag-
matic hernias (CDH) are left sided; in these
PEARLS AND PITFALLS patients, there can be herniation of the small
• It is important to recognize that visual estima- or large bowel and other solid intra-abdominal
tion of the degree of jaundice can lead to organs. Patients with CDH who require
errors, particularly in darkly pigmented ECMO have worse prognosis than those who
infants. do not require ECMO.
• Infants < 38 weeks gestation, particularly • In newborns who present with bilious vomit-
those who are breastfed, are at higher risk of ing, one of the most important diagnoses to
developing hyperbilirubinemia and require exclude is malrotation with or without
closer surveillance and monitoring. volvulus.
• All bilirubin levels should be interpreted • Infants with volvulus constitute a surgical
according to the infant’s age in hours. A sys- emergency and require prompt medical and
tematic assessment for the risk of severe surgical intervention. Up to 80% of affected
hyperbilirubinemia should be performed on patients receive a diagnosis during the neona-
all infants before discharge. tal period, with 50% presenting in the first
• The most common bacterial pathogen for week after birth. If not recognized in a timely
early onset sepsis is GBS, followed by E. coli. fashion, volvulus can lead to catastrophic loss
• HSV PCR testing in the asymptomatic new- of bowel with resultant lifelong disability and
born should be delayed for 24–48 h after birth even death.
in order to differentiate viral replication in the • Gastroschisis presents as a full thickness
newborn from transient colonization of the defect in the abdominal wall with prolapse of
newborn at birth. the intestine through the defect. There is no
• The congenital infection most commonly covering membrane, and the defect lies to the
associated with hydrops fetalis is parvovirus right side of an intact umbilical cord.
B19. • In omphalocele, the defect is midline and the
• The most common cause of respiratory dis- prolapsed organs are always covered with a
tress in the term newborn is transient tachy- protective membrane consisting of amnion on
pnea of the newborn (TTN). This is a the outer surface, peritoneum on the inner
self-limited disorder and usually resolves surface, and Wharton jelly in between.
within 48 h. • Omphaloceles contain a variable amount of
• Nonvigorous newborns with meconium- intestine, often parts of the liver, and occa-
stained amniotic fluid do not require routine sionally other organs.
intubation and tracheal suctioning. However, • There is no evident genetic cause for gastros-
meconium-stained amniotic fluid is a perina- chisis; associated intestinal atresias may be
tal risk factor that requires the presence of present. In contrast, omphaloceles are associ-
one resuscitation team member with full ated with syndromes and chromosomal
2 Neonatology 79
abnormalities in over 50% of cases, including Campbel DE. Neonatology for primary care.
Beckwith-Wiedemann syndrome (omphalo- Elk Grove Village: American Academy of
cele, macroglossia, organomegaly, hypogly- Pediatrics; 2015.
cemia, and increased risk for childhood Gornall AS, Kurinczuk JJ, Konje JC. Antenatal
tumors such as Wilms tumor, neuroblastoma, detection of a single umbilical artery: does it
and hepatoblastoma). matter? Prenat Diagn. 2003;23:117–23.
Hibbs AM, Black D, Palermo L, Cnaan A, Luan X,
Truog WE, et al. Accounting for multiple births
in neonatal and perinatal trials: systematic review
and case study. J Pediatr. 2010;156:202–8.
References
Laptook A, Tyson J, Shankaran S, McDonald S,
1. Fernandes CJ. Neonatal resuscitation in the Ehrenkranz R, Fanaroff A, National Institute of
delivery room. In: Post TW, editor. UpToDate. Child Health and Human Development Neonatal
Waltham: UpToDate. http://www.uptodate.com. Research Network, et al. Elevated tempera-
Accessed 13 Jan 2019. ture after hypoxic-ischemic encephalopathy:
2. Maisels MJ, Watchko JF, Bhutani VK, Stevenson risk factor for adverse outcomes. Pediatrics.
DK. An approach to the management of hyper- 2008;122:491–9.
bilirubinemia in the preterm infant less than 35 Ment LR, Bada HS, Barnes P, Grant PE, Hirtz
weeks of gestation. J Perinatol. 2012;32:660–4. D, Papile LA, et al. Practice parameter: neuro-
3. American Academy of Pediatrics Subcommittee imaging of the neonate: report of the Quality
on Hyperbilirubinemia. Management of Standards Subcommittee of the American
hyperbilirubinemia in the newborn infant Academy of Neurology and the Practice
35 or more weeks of gestation. Pediatrics. Committee of the Child Neurology Society.
2004;114:297–316. Neurology. 2002;58:1726–38.
Norton ME, Scoutt LM, Feldstein VA, editors.
Callen’s ultrasonography in obstetrics and gyne-
Suggested Reading cology. 6th ed. Philadelphia: Elsevier; 2017.
Wyckoff MH, Aziz K, Escobedo MB, Kapadia
Barnes-Powell LL. Infants of diabetic mothers: the VS, Kattwinkel J, Perlman JM, et al. Part 13:
effects of hyperglycemia on the fetus and neo- neonatal resuscitation: 2015 American Heart
nate. Neonatal Netw. 2007;26:283–90. Association guidelines update for cardiopul-
monary resuscitation and emergency cardio-
vascular care. Circulation. 2015;132(18 Suppl
2):S543–60.
Adolescent Medicine
3
Jessica Addison
PHYSIOLOGICAL CHANGES Menarche: Time of first menstrual bleeding

• Menarche usually starts 2–3 years after breast
AND DEVELOPMENT DURING development
ADOLESCENCE • The first menstrual bleed is often not associ-
ated with ovulation
uberty Sequence in Girls
P • Girls who develop earlier (or later) than their
peers in school may face psychological
• Puberty for girls generally lasts an average of challenges
4 years (1.5–8 years)
Thelarche: Appearance of breast tissue

uberty Sequence in Boys
P
• Enlargement of the breast is the earliest sign
of puberty • Puberty in boys usually lasts an average of
• Mean age 9.7 years (7.8–11.6 years) in 3 years (2–5 years)
Caucasian girls
• Mean age 8.8 years (6.1–10.1 years) in Increase in testicular volume
African-American girls • Enlargement of the testicles is the earliest
sign of puberty
Pubarche: The appearance of pubic hair; first • The mean age is 11.4 years (9.5–13.5 years)
appearance of axillary hair, apocrine body odor, • Expected growth: Volume ≥ 4 mL and length
and acne ≥ 2.5 cm
Peak height velocity Penile growth
• Occurs about 6 months prior to menarche • Growth in length rather than width. Pubic
• Occurs at a mean age of 11.5 years in girls hair is getting darker and coarser
• Approximately 8.3 cm/year
Pubarche
• Appearance of axillary hair, apocrine body
odor, acne, and voice changes
J. Addison (*)
Division of Adolescent/Young Adult Medicine, Department of Peak height velocity
Pediatrics, Boston Children’s Hospital, Harvard Medical School, • Occurs at a mean age of 13.5 years in boys
Boston, MA, USA
e-mail: Jessica.Addison@childrens.harvard.edu
• Is approximately 9.5 cm/year

82 J. Addison
Table 3.1 Tanner staging [1, 2]

Stage Pubic hair Male genitalia Female breasts
1 No pubic hair No signs of puberty testicular No breast tissue
volume < 4 mL
2 Sparse hair that are straight Enlargement of the scrotum and Breast tissue formation (breast bud)
and lack pigment testes. Reddening of scrotum Widening of areola
3 Coarse, dark, curly hair Elongation of penis Continued enlargement of breast and
areola with no separation of contour
4 Pubic hair dense, curly, Continued growth of testes and Areola and nipple project above breast
pigmented (does not reach penis tissue (secondary mound)
medial thigh)
5 Adult hair growth Testicular volume > 20mL Adult pattern
Pubic hair spreads to the
medial thigh
Skeletal growth • Smoking and illicit drugs

• The growth spurt in girls occurs earlier than • Obesity
in boys, sexual maturity rating (SMR) II–III • Gynecomastia
for girls vs. SMR IV for boys • Mental health
• Girls reach their final height earlier than boys
(average 16 years for girls vs. 18 years for Cognitive development [3]
boys) • Early adolescence (10–13 years old): Concrete
thinking, egocentrism, and impulsive behavior
Tanner staging (Table 3.1) [1, 2] • Middle adolescence (14–16 years old):
Abstract thinking
Hematological changes • Late adolescence (17–21 years old):
• In boys, blood volume, red blood cell (RBC) Becoming a separate entity from family
mass, hemoglobin, and hematocrit all increase
during puberty under the effect of testoster- Identity development
one (this is not the case with girls) • Early: Privacy, self-exploration, testing
authority, and lack of impulse control
Risks and conditions associated with death dur- • Middle: Feelings of omnipotence, immortal-
ing adolescence ity, and engaging in risk-taking behavior
• Unintentional injuries such as motor vehicle • Late: Rational and realistic conscience with
accidents are the leading causes of adolescent the ability to delay gratification, to compro-
morbidity and mortality mise, and to set limits
• Suicide is the second leading cause of death
among adolescents Management of poor self-image
• Most of the adolescent’s medical care is • Perception of self is shaped by personal goals,
received in the emergency department life experiences, ethnicity, religion, and sex-
ual identity
Reasons for hospitalizations • Risk factors for poor self-image: Neglect and
• Number 1: Pregnancy abuse, mental health problems, poverty, wit-
• Number 2: Mental disorders nessing or experiencing trauma
• Number 3: Injuries • Signs of poor self-esteem/self-image: Mood
changes, poor school performance, substance
Common problems abuse, risk-taking behaviors
• Pregnancy • Management: Family support and acceptance,
• Acne focusing on individual strengths, emphasizing
3 Adolescent Medicine 83
that adolescence is a time of self-growth and • Discussing sexuality will not cause adoles-
discovery and that they are not alone cents to become sexually active if they have
not started already
Psychological separation from the family and
peer group relationships [3]
• Separation occurs during late adolescence Emancipation and Healthcare
and shapes personal development but can also Decisions [4]
be linked to start of risk-taking behaviors
• Peer group development Emancipated minors
–– Early (10–13 years old): Dependent on • Process where a minor (< 18 years of age) is
friends, nonromantic relationships legally declared an adult
–– Middle (14–16 years old): Peer group most • Examples of an emancipated minor include
powerful, includes romantic relationships, those who are married, active member of mil-
involvement with clubs, team sports, gangs, itary, moved from the parental home and pay-
and other groups of interest ing their own bills, and being a parent
–– Late (17–21 years old): Peer group values
become less important, separate identity Mature minor doctrine
from parents, more time spent in a relation- • Allows minor to consent to routine, nonemer-
ship with one individual gency care, especially when the risk of treat-
ment is considered to be low
Family influence on adolescent behavior • Must be able to understand the risks and ben-
• Parents’ behavior significantly influences the efits of treatment plan and be able to provide
behavior of their children the same level of consent as an adult
• If parents are viewed in a positive way and • Many states allow minors to seek help for
exhibit high self-esteem, their child is more pregnancy, contraception, substance abuse,
likely to model them sexually transmitted disease (STD), and men-
• If a parent is viewed in a negative way, the tal health issues without parental consent
child may mimic negative attitude and gener-
alize it to the rest of society Best approach in difficult cases
• Support from parents helps develop positive • Encourage the minor to agree to bring the par-
bonds with the adolescent, which hinders the ents or guardian into decision-making pro-
formation of deviant behaviors cess, with the physician acting as a facilitator
Sexuality Adolescent Routine Health Visit
• It is important to normalize sexual behavior Interview

(e.g., sexual intercourse, masturbation), sex- • Allow adolescents to become autonomous,
ual identity and exploration involve the parents only as much as the ado-
–– Adolescents are at increased risk for sexu- lescent wishes
ally transmitted infections and pregnancy, • Interview the adolescent alone and in a confi-
so counseling regarding safe sex practices dential manner when discussing drugs, con-
is recommended at all visits traception, STDs, and mental health.
• Open, honest communication regarding sexu- Confidentiality can be broken if it appears the
ality between adolescents and their parents is adolescent is a harm to themselves or others
strongly encouraged (e.g., actively suicidal)
84 J. Addison
Laboratory
• Annual screening for chlamydia and gonor-
rhea infection in all sexually active women
< 25 years of age
• Screening for chlamydia in sexually active
adolescent men should be considered in clini-
cal settings where there is a high prevalence
• Universal cholesterol for youth 9–11 years
old; a second screening for youth between 17
and 21 years old or those with a family his-
tory of early cardiovascular disease
• Consider obtaining a complete blood count
(CBC) in adolescent females starting at age
12 if risk factors are identified for anemia
(history of poor dietary iron intake, heavy
Fig. 3.1 An adolescent female with severe thoracolumbar
scoliosis
menstrual blood loss)
• Screening for HIV infection should be per-
• Ask about peer and family relationships, formed, at least once for all patients between
depression, sexual relationships, substance 15 and 18 years old
abuse, and eating disorders
Physical examination Immunization

• Hearing and vision • At 11–12 years, give Tdap vaccine (against
• Blood pressure tetanus, diphtheria, and pertussis), meningo-
• Scoliosis: Current evidence is insufficient to coccal conjugate vaccine (MCV4), and
recommend screening for scoliosis in adoles- human papilloma virus (HPV) vaccine;
cents < 18 years of age and that the balance of 3-dose series if started after the age of
benefits and harms of screening for adoles- 15 years old, 2-dose series if started before
cent idiopathic scoliosis cannot be deter- that age
mined [5] (Fig. 3.1) • At 16 years, give a booster dose of MCV and
• Visual breast examination consider Bexsero (2 doses 1 month apart) or
• Pelvic examination Trumenba (2 doses 6 months apart) for
–– Indications for pelvic exam in an adoles- healthy adolescents
cent: Persistent vaginal discharge, dysmen-
orrhea refractory to medical management, Anticipatory guidance
amenorrhea, abnormal vaginal bleeding, • Promote injury prevention
lower abdominal pain. Routine cervical • Seat belt use all the time
screening at age 21 • Alcohol/substance abuse
• External genital exam to evaluate for masses, • Helmet use
hernia, varicocele, hydrocele, appropriate • Weapon safety
size of testes, or other pathology. Vaginal • Exercise preparedness to prevent injury
exam to evaluate for cysts, abnormal dis- • Risky behaviors
charge, genital warts, irritation, clitoromeg- • Indication for intervention in cases of obesity
aly, or other pathology (Table 3.2)
• Calculate body mass index (BMI) • Screen for eating disorder behaviors
Table 3.2 Indication for intervention in cases of obesity • Teaching adolescents to listen and communi-
BMI ≥ 95th percentile
* cate with one another in an effort to develop
Or empathy and understanding can assist in con-
BMI between 85th and 95th percentile and flict resolution
Family history of premature heart disease, obesity,
HTN*, or DM*
• Opportunities to discuss conflict/anger with
HTN adults or peers offer alternative perspectives
Cholesterol > 200 mg/dL and can result in calm, rational decision-mak-
Increase of ≥ 2 points in BMI in 12 months ing instead of impulsivity and violence
Adolescent is concerned about his or her weight
BMI body mass index, HTN hypertension, DM diabetes
*
Stress
mellitus • Can manifest in a variety of ways in adoles-
cents: Clinical symptoms (e.g., abdominal
BEHAVIORAL HEALTHCARE pain, headache), mood changes (e.g., depres-
sion), poor school performance, sleep distur-
General bance, and behavioral changes
• It is important to take a developmentally
appropriate psychosocial history during each
interaction with an adolescent SUBSTANCE ABUSE
(TABLE 3.3) [6]
Adherence
• Factors that negatively affects adolescents’ • American Academy of Pediatrics (AAP) rec-
adherence to medical regimens: Mental health ommends annual substance use screening of
issues, peer influence, family stressors, cogni- all adolescents, starting at 9 years of age, and
tive change (e.g., concrete to abstract thinking), use of brief intervention techniques
poor access to healthcare, independence from
family (e.g., now making their own decisions) Background
• Factors that positively affect adolescents’ adher- • Marijuana, alcohol, and tobacco are the most
ence to medical regimens: Positive family rela- commonly used substances during adolescence
tionships, self-control, treatment with immediate • Mean age of smoking is 12 years, and 12.6 years
benefits, positive patient–clinician relationship for alcohol consumption
• The earlier an adolescent begins using sub-
Risk-taking stances, the greater the risk of developing
• Factors associated with risk taking behaviors: substance use problems as an adult. Boys
Peer influence, mental health issues, family have a lower age of smoking initiation com-
stressors, adversity and stress, neuropsycho- pared to girls.
logical changes (brain development)
Stages of drug/alcohol abuse
Violence • Abuse
• There is a high occurrence of sexual assault –– Substance use resulting in failure to meet
in the adolescent population, which has nega- obligations (e.g., school or work)
tive medical, social, and psychological –– Using substance in situations that can
consequences cause harm (e.g., driving a car)
• All adolescents should be screened for sexual –– Continued use despite having negative
victimization effects on interpersonal relationships
86 J. Addison
Table 3.3 Substance abuse, intoxications, and means of administration [6]

Substance abuse Consequence and intoxications Means of administration
Alcohol Euphoria, grogginess, talkativeness, impaired short-term Drinking
memory, diuresis, gastritis, hypothermia, decreased
coordination, road crashes, respiratory depression,
transaminitis, pancreatitis, gastrointestinal symptoms
Marijuana Euphoria, poor performance of tasks requiring divided Smoking
attention, loss of critical judgment, distortion of time
perception, road crashes, injected conjunctiva, tachycardia, dry
mouth, respiratory symptoms (worsening of asthma)
Opioids Euphoria, diminution of pain, flushing of skin, pinpoint pupils, Injected (IV/SC), snorted/
tracks (skin lesions follow large veins), skin abscesses (use of sniffed, or smoked
unsterile needles), loss of libido, increased risk of STDs (e.g.,
HIV), constipation, endocarditis, cerebral micro-abscesses,
respiratory depression, coma, death
Amphetamine Increased physical activity, rapid and/or irregular heart rate, Ingested orally, smoking,
increased blood pressure, decreased appetite, psychosis, injection, mucosal absorption
violence, increased risk of STDs, withdrawal syndrome or
crash phase (depression, agitation, craving for more drug),
limited interest in the environment, anhedonia
Hallucinogen—(LSD) Delusional ideation, altered changes in vision and hearing, Drinking (liquid or tablets)
body distortion, distortion of time, suspiciousness, toxic
psychosis, dizziness, dilated pupil, nausea, flushing, decreased
temperature, tachycardia (not addictive)
Hallucinogen—MDMA Euphoria, heightened sensual awareness, increased psychic Drinking (tablets or capsules)
(“X,” ecstasy) and emotional energy, nausea, jaw clenching, teeth grinding,
blurred vision, anxiety, panic attacks, and psychosis
Hallucinogen—PCP Euphoria, nystagmus, ataxia, emotional lability, shallow Drinking (tablets, liquids, or
breathing, flushing, generalized numbness of extremities, loss powder), e.g., angel dust and
of motor coordination, bizarre distortion of body image, panic peace pill
reactions, disorientation, hypersalivation, abusive language,
seizures, cardiac arrhythmias, death (dose-related)
Cocaine Euphoria, increased motor activity, decreased fatigability, Smoking, snorting, injection
pupillary dilatation, tachycardia, hypertension, anxiety,
psychosis
(Snorting cocaine: loss of sense of smell, nosebleeds, chronic
rhinorrhea, destruction of nasal septum)
Inhalants Euphoria, slurred speech, decreased coordination, dizziness, Inhalation, e.g., toluene found
violent excitement, brain damage, coma from prolonged use. in paint thinners and removers
Death from cerebral edema, pulmonary edema, or myocardial
involvement
STD sexually transmitted disease, IV intravenous, SC subcutaneous, LSD lysergic acid diethylamide, MDMA
3,4-methylenedioxy-methamphetamine, PCP phencyclidine
• Tolerance • Addiction
–– No longer responds to the same amount of –– No longer for pleasure, physical and psy-
substance chological need to use substance
–– Needs increased amounts of substance to –– Continues to use drug despite negative
achieve intoxication or desired effect consequences
• Dependence
–– Can only function normally when on sub- Tobacco
stance and experiences withdrawal symp- • Tobacco use by adolescents can become a
toms if off drug serious drug addiction
• Adolescents underestimate the addictive • Psychiatric conditions (anxiety and depres-

nature of cigarettes sion) often occur with alcohol use
• There has been an increase in e-cigarette use
in adolescents, which can serve as a gateway Marijuana
drug to traditional cigarette smoking • Can have permanent negative effects on the
• Systemic effects of tobacco developing adolescent brain
–– Cardiovascular disease • Most common illicit drug used by adolescents
–– Cancers • Adverse psychosocial outcomes: Poor school
–– Diminished bone density performance, impaired peer and family rela-
–– Pulmonary effects (worsening asthma) tionships, mood changes, and impaired
–– Gastrointestinal effects (gastroesophageal memory
reflux)
–– Reproductive effects (pregnancy) Opioids
• Assess adolescents’ willingness to quit smok- • Physiologic consequences: Hypotonia, respi-
ing at each clinical encounter ratory failure, hypotension, miosis, coma
• Tailor counseling around helping adolescents • Acute overdose management: Airway, breath-
identify their own benefits and barriers to ing, and circulation (ABCs), naloxone IV
quitting
Amphetamines
• Nicotine replacement therapies are available
• Nonmedical use of prescription amphetamine
over the counter for those > 18 years of age
is increasing among adolescents
and by prescription for adolescents < 18 years
• Antipsychotics and/or benzodiazepines are
• Bupropion or varenicline can be considered
used in cases of acute intoxication for agita-
for treatment of adolescents with moderate to
tion management
severe nicotine addiction
• School and community support program Hallucinogens
–– Mobile phone–based programs • Adverse effects from chronic use: Psychosis,
–– Proactive community-wide telephone sup- depression, and personality changes
port combined with patient education • Hallucinogen use should be on differential
materials diagnosis in an adolescent presenting with
• E-cigarettes counselling new-onset psychosis
–– AAP recommends screening all family mem- • Treatment of acute intoxication/overdose is
bers for e-cigarette use, counsel all children supportive, preferably in a calm environment
and youth about the potential harms of e-cig-
arettes, and promote family strategies to Cocaine
avoid exposure to e-cigarettes, including ban-• Signs of cocaine intoxication: Hypertension,
ning their use from the household and car hyper-alertness, tachycardia, dilated pupils,
hyperactive reflexes
Alcohol • Management and treatment of cocaine over-
• Alcohol use is common during adolescence, dose: Respiratory, renal (rhabdomyolysis),
and initiation at an early age is associated cardiovascular (electrocardiographic, cardiac
with future alcohol-related problems and sub- enzymes) support and monitoring
stance abuse
• Alcohol use contributes to the leading causes Inhalants
of adolescent death (e.g., motor vehicle acci- • Used by inhaling from a plastic bag (“bag-
dents and suicide) ging”) or by inhaling through a cloth satu-
rated with substance (“huffing”)
88 J. Addison
• Products used as inhalant substances: Toluene • Increased school absence

(found in spray paint), cleaning fluids, rubber • Suicide attempt
cement, and permanent markers • Altered mental status
• Inhalant abuse is a significant risk of “sudden
sniffing death syndrome” → cardiac arrest Consent for drug testing
• Sudden death may occur in all inhalant users, • Drug testing of older competent adolescent
including those experimenting with inhalant should be voluntary
abuse for the first time.
• Treatment is supportive and includes respira-
tory and circulatory support EATING DISORDERS
Over-the-counter and prescription medicine Introduction
• Commonly abused over-the-counter medica- • Eating disorders are serious mental health
tions: Cold medicines (pseudoephedrine), conditions in children, adolescents, and
cough medicines (dextromethorphan), anal- young adults
gesics (acetaminophen) • These disorders can cause significant morbid-
• Commonly abused prescription medications: ity and mortality, as well as devastating
Stimulants, opioids, sedatives, anxiolytics effects on the child’s psychosocial develop-
• Risk factors for abuse of over-the-counter and ment, family dynamics, and education
prescription medicine • Anorexia nervosa has the highest fatality rate
–– Family history of substance abuse prob- of any mental health disorder
lems, history of or current substance use,
peer pressure, easy access to prescription Suspicious behaviors
drugs (personal prescription or family • Assumption of a vegan, vegetarian, low fat,
member has prescription), lack of knowl- or “healthier” diet, scrutiny of ingredient lists
edge regarding potential harm • Initiation of precise calorie counting or
weighing one’s self several times daily
Anabolic steroids • Taking smaller portions or taking a longer
• Can be taken as an oral or injectable agent period of time to eat
• Adverse effects: Psychiatric (mood changes), • Increasing the duration and intensity of exer-
cardiovascular (hypertension), endocrine cise in an attempt to utilize more energy
(premature epiphyseal closure, testicular • Avoiding eating with family and friends or
atrophy), dermatologic (acne) hiding food during social meals
• Signs of purging activity include frequent
Red flags of substance abuse trips to the bathroom after meals
• Behavioral problems • Discovery of empty containers of diet pills or
• School failure laxatives
• Emotional distress • Extra layers of clothing to cover up signs of
• Absent or hostile communication emaciation and to retain body heat
• Risky behaviors
• New disinterest in sports Indication of hospitalization of patients with
eating disorders
Indications of substance abuse screening • Weight < 75% of ideal body weight for age,
• Unexplained accidents gender, and stature
• Trauma • Acute weight decline and refusal of food
• Psychiatric symptoms • Hypothermia
• School failure or deterioration • Hypotension
• Bradycardia Table 3.4 Diagnostic criteria for anorexia nervosa

• Arrhythmia Criterion DSM-V
• Syncope Body Restriction of energy intake relative to
• Suicidal risks weight requirements leading to a markedly low body
weight (less than minimally expected for age
• Electrolyte disturbance and height)
• Failure to respond to outpatient treatment Fear of Intense fear of gaining weight or becoming fat,
weight although underweight, or persistent behavior to
gain avoid weight gain, although at a markedly low
Anorexia Nervosa weight
Body Disturbance in the way one’s body weight or
image shape is experienced; denial of the seriousness
Background
of low body weight; undue influence of body
• Anorexia is divided into two subtypes: Binge/ weight or shape on self-evaluation
purging and restrictive DSM-V Diagnostic and Statistical Manual of Mental
• Anorexia nervosa is a potentially life-threat- Disorders-V
ening eating disorder characterized by the
inability or refusal to maintain a minimally • EKG
normal weight, a devastating fear of weight • Metabolic panel
gain, relentless dietary habits that prevent • Urinalysis
weight gain, and a disturbance in the way in • Pregnancy test (in females of childbearing age)
which body weight and shape are perceived
• Individuals usually involved in ballet or Complications of anorexia nervosa [7]
sports, e.g., gymnastics, wrestling, running • Gastrointestinal
marathons –– Gastric dilatation and rupture, delayed gas-
tric emptying, decreased intestinal motility,
Clinical presentation (Table 3.4) elevated liver aminotransferase concentra-
• Hypotension, bradycardia, and hypothermia tions, elevated serum amylase concentra-
• Dry skin tions, superior mesenteric artery syndrome
• Lanugo-like body hair • Cardiovascular
• Thinning hair –– Decreased left ventricular forces, pro-
• Swelling of the parotid and submandibular longed QT interval corrected for heart rate,
glands increased vagal tone, pericardial effusion,
• Atrophy of the breasts congestive heart failure
• Patients with purging behavior may have cal- • Hematologic
luses to the dorsum of their dominant hand –– Anemia, leukopenia, thrombocytopenia
and dental enamel erosion • Endocrine and metabolic
• Loss of muscle mass –– Low bone density, euthyroid sick syn-
• Low blood glucose (impaired insulin drome, amenorrhea, refeeding syndrome,
clearance) electrolyte disturbances, decreased serum
• Low parathyroid hormone levels testosterone or estradiol, hypercholesterol-
• Elevated liver function emia, hypercortisolism
• Low white blood cell (WBC) count • Renal
–– Increased blood urea nitrogen, calculi
Laboratory formation
• CBC • Neurological
• TSH –– Pseudo-cortical atrophy, enlarged
• ALT ventricles
90 J. Addison
Management Table 3.5 Diagnostic criteria for bulimia

• The process of refeeding must be undertaken Criterion DSM-V
slowly, with modest increases in metabolic Binge eating Eating an amount of food in a discrete
demands, in order to avoid refeeding period of time (2 h) that is definitely
larger than most people would eat
syndrome Compensatory Recurrent inappropriate compensatory
• Refeeding syndrome: As the adolescent’s behavior behavior in order to prevent weight gain
caloric intake increases, low levels of serum such as self-induced vomiting, misuse of
phosphorus can lead to: laxatives, diuretics, enemas, other
–– Rhabdomyolysis medications, fasting, or excessive exercise
Frequency of Binge eating and inappropriate
–– Decreased cardiac motility, above compensatory behaviors both occur, on
cardiomyopathy behaviors average, at least once a week for 3 months
–– Respiratory and cardiac failure Self- Unduly influenced by body shape and
–– Edema, hemolysis, acute tubular necrosis evaluation weight
–– Seizures and delirium Relation to The disturbance does not occur
anorexia exclusively during episodes of anorexia
–– Dangerous fluctuations in potassium, nervosa nervosa
sodium, and magnesium levels DSM-V Diagnostic and Statistical Manual of Mental Disorders-V
• A nutritionist or dietitian should be an inte-
gral part of the refeeding
• Psychological therapy, e.g.: • Irregular menses
–– Individual therapy (insight-oriented) • Throat pain
–– Cognitive analytic therapy • Bilateral parotid gland swelling
–– Cognitive behavioral therapy • Calluses on the dorsum of the fingers and loss
–– Family-based therapy of tooth enamel from acidic vomit
• Aspiration pneumonia
• Metabolic alkalosis
Bulimia • Elevated serum amylase
Background Management
• Bulimia is divided into two subtypes: Purging • Psychological therapy
and non-purging • Management of associated conditions, e.g.,
• Binge eating is seen in both subtypes obsessive, compulsive, or affective
• The purging subtype describes an individual disorders
who engages regularly in self-induced vomiting • Pharmacological therapy: Consider selective
or misuse of laxatives, diuretics, or enemas serotonin reuptake inhibitors (SSRIs), e.g.,
• The non-purging subtype describes an indi- fluoxetine
vidual who uses other inappropriate compen-
satory behaviors, such as excessive exercise
or fasting to burn calories FEMALE BREAST MASSES
• It is important to note that patients who have
bulimia often are not low weight and thus Introduction
may easily hide their eating disorder • Estrogen is the most important factor in breast
development.
Clinical presentation (Table 3.5) • Asymmetrical growth of breasts where one is
• Fatigue slightly bigger than the other is normal.
• Bloating
• The most common breast masses are s olitary • Ultrasound can be used for screening (mam-
cysts, fibrocystic changes, and fibroadenoma mography not used for adolescents)
• Breast cancer in adolescence is extremely
rare
• Family history is extremely important
AMENORRHEA
Solitary cyst [8]
• It is a benign breast mass Primary amenorrhea
• > 50% of cases resolve spontaneously in • Absence of menarche by 15 years old
2–3 months
• Follow up with serial exams Secondary amenorrhea
• Breast ultrasound if cannot differentiate • Loss of menses for > 3 consecutive months
between cystic and solid mass by physical after previous regular cycles
examination • Loss of menses for 6 months in those with
• Pain is commonly associated with solitary previously irregular cycles
cystic masses
• Nonsteroidal anti-inflammatory drug Causes of amenorrhea (Fig. 3.2) [9]
(NSAID) can be used for pain • Pregnancy is the most common cause of sec-
• Oral contraceptives may reduce the frequency ondary amenorrhea
and duration • Central (hypothalamic or pituitary).
• Ovarian or anatomic (uterus, cervix, vagina,
Fibroadenoma [8] imperforate hymen)
• Fibroadenoma is the most common breast • Polycystic ovarian syndrome (PCOS)
mass that usually presents as a single breast • Prolactinoma, thyroid dysfunction, weight
mass in young women loss (anorexia)
• Discrete solitary breast mass of 2–3 cm
located in the upper outer quadrant in major- Clinical approach to an adolescent with second-
ity of cases ary amenorrhea
• Fibroadenoma is usually smooth, mobile, • Perform history and physical and review
nontender, and rubbery in consistency medications (are they on contraception?)
• They have no malignant potential • Assess estrogen status with progesterone
challenge
Cystosarcoma phyllode
• Labs and imaging:
• Rare, rapidly growing lesion with a small risk
–– Pregnancy test
of becoming malignant
–– Luteinizing hormone (LH)
–– Follicle-stimulating hormone (FSH) (if
Intraductal papilloma elevated, consider premature ovarian insuf-
• Benign, slow-growing tumor located under ficiency and consider karyotype to rule out
the areola Turner syndrome)
• It may present with a serous or bloody –– Thyroid-stimulating hormone (TSH)
discharge –– Prolactin (if elevated, consider brain mag-
netic resonance imaging (MRI) to rule out
Indication for surgical intervention prolactinoma)
• Persistence of a mass or enlargement over –– Assess for biochemical signs of
three menstrual cycles hyperandrogenism
92 J. Addison
Initial tests: Pregnancy test, LH, FSH, TSH, prolactin level, and
pelvic ultrasound Pregnancy positive: exclude ectopic and
refer to OBGYN
TSH is abnormal: order complete thyroid
function
Uterus Prolactin is elevated: order brain MRI
Yes No
Genetic testing, total and free

testosterone
Normal FSH
High FSH & LH Low FSH & LH
& LH
46 XY and high 46 XX and normal

Testosterone Testosterone
Primary ovarian Outflow Constitutional delay,

failure obstruction anorexia nervosa,
e.g., Turner syndrome GnRH deficiency Androgen
Mullerian agenesis
insensitivity
Fig. 3.2 Approach to the adolescent with primary amenorrhea. LH luteinizing hormone, FSH follicle-stimulating hormone,
TSH thyroid-stimulating hormone. MRI magnetic resonance imaging, GnRH gonadotropin-releasing hormone [9]
◦◦ Free and total testosterone (if elevated, D

ysmenorrhea
consider PCOS)
◦◦ 17 hydroxyprogesterone (if elevated, Background
consider late-onset congenital adrenal • Leading cause of school absenteeism in
hyperplasia) female adolescents
◦◦ DHEA-S (if elevated > 500 μ/dL, obtain –– Due in most cases to prostaglandin pro-
abdominal MRI or computed tomogra- duction before menses, which causes
phy [CT] scan) vasoconstriction and muscular
• Consider pelvic ultrasound to evaluate for contractions
anatomic abnormality
• Abdominal pain and cramps
Polycystic Ovarian Syndrome (PCOS)
Differential diagnosis
• Characterized by oligo-/anovulatory cycle • Anatomic abnormality
and hyperandrogenism (clinical and/or • Pelvic inflammatory disease (PID)
biochemical) • Endometriosis
• Increased risk for metabolic abnormalities • Psychosocial (e.g., trauma, stress)
(insulin resistance and hyperlipidemia)
• Pharmacologic treatment: Combined hor- Management
monal contraceptives, cyclic progestins • Ibuprofen, naproxen
(induces withdrawal bleed), metformin (low- • Contraceptives are very effective in reducing
ers insulin levels and decreases steroid hor- or eliminating dysmenorrhea
mone production by ovaries)
Dysfunctional Uterine Bleeding

• The most common cause of excessive bleeding
that requires hospitalization in adolescence
• During the first 2 years after menarche, men-
strual cycles are typically anovulatory, which
can result in irregular bleeding
• Abnormal bleeding at the time of menarche
may be the first sign of a bleeding disorder,
e.g., Von Willebrand disease
• Lacerations of vagina, hymenal tear, and for-
eign bodies may present with vaginal bleeding
• Differential diagnosis of dysfunctional uter-
ine bleeding:
–– Vaginal adenocarcinoma in girls because
their mothers received diethylstilbestrol
(DES)
–– Thyroid dysfunction, hyperprolactinemia,
hypothalamic dysfunction
–– Bleeding disorder
–– Anovulatory cycles
–– Structural lesions, cervical polyps
–– Endometrial diseases, e.g., endometritis
–– STDs
Imperforate Hymen (Fig. 3.3) [10] Fig. 3.3 Imperforate hymen. (From Emans and Laufer [10],
with permission)
• Common obstructive lesions of the female
genital tract
• Associated with amenorrhea, cyclic pelvic Ovarian Torsion
pain, and accumulation of blood in the vagina
(hematocolpos) • Clinical symptoms
• Treatment: Surgical correction –– Sudden onset of unilateral pelvic pain that
worsens over hours, adnexal mass, nausea,
and vomiting. Fever may occur as the ovary
Labial Adhesions becomes necrotic
• Diagnosis
• Clinical symptoms: Asymptomatic, urinary –– Ultrasonography with color Doppler anal-
symptoms, vaginal symptoms (pain, dis- ysis is the method of choice for the evalua-
charge, and infection) tion of adnexal torsion
• Management: Topical estrogen or estradiol; • Treatment
consider surgery if no response to medical –– Immediate gynecologic consultation and
management subsequent laparoscopy are critical
94 J. Addison
Ovarian Cyst • Anabolic steroids

• Frequent marijuana use
• Presents with lower abdominal pain
• Evaluation
–– History (menstrual history) and physical Scrotal Masses
–– Labs: Pregnancy test, CBC (in setting of
heavy menstrual bleeding), STI testing • Neoplasm usually presents as a painless mass
–– Ultrasound: Adnexal mass and fluid in the that may be discovered accidentally by
pelvis suggest a ruptured ovarian cyst but self-examination
is not diagnostic • May present with pain if hemorrhage or
• Treatment is observational vs. surgical (if necrosis occurs
hemodynamically unstable or large cyst) • Back pain if retroperitoneal lymph node is
present
• 95% of testicular tumors are germ cell in
Gynecomastia (Fig. 3.4) origin, e.g., seminoma, embryonal carci-
noma, teratoma, and choriocarcinoma.
• Occurs in 50% of boys between 10 and Other 5% are of stromal tissue origin
16 years • Human chorionic gonadotropin (HCG) is ele-
• The area may be tender and asymmetric vated in choriocarcinoma
• Most gynecomastia resolves spontaneously • α-Fetoprotein is elevated in a yolk sac tumor
• Benign pubertal gynecomastia is usually and embryonal carcinoma
< 4 cm and does not need any specific workup • Most seminomas do not produce any
or therapy markers
• Large breast similar to female breast SMR II– • Investigation includes testicular ultrasonog-
III or more is unlikely to resolve spontane- raphy and CT scan of the chest and
ously and may require surgery abdomen
• Treatment includes orchiectomy, peritoneal
Rare causes of gynecomastia lymph node dissection, radiation therapy, and
• Klinefelter syndrome chemotherapy, depending on staging
• Tumor of testicular, adrenal, or pituitary glands
Fig. 3.4 Male adolescents with different degrees of gynecomastia

Contraception • Smoking (> 35 years of age)

• Known or suspected pregnancy
Background
• Providing adolescents with accurate infor- Relative contraindication of oral contraceptive
mation about contraception is important. • Tobacco use
The choice of contraceptive method is a • Diabetes mellitus
complex decision and healthcare providers • Seizures
should create a supportive, nonjudgmental, • Migraine
and confidential environment • Hypertension
• The discussion should be patient-centered
when providing contraceptive counseling Emergency contraception
• Topics such as: goals of using contraception, • Levonorgestrel (Plan B) is available over the
safety in relationship (e.g, intimate partner counter or by prescription with no age
violence, coercion), and reproductive health restriction
(e.g, STI prevention) should be discussed • Ulipristal acetate (Ella) is available by pre-
with the adolescents scription with no age restriction
• Most effective if used as soon as possible
Contraceptive Methods but also up to 120 h after unprotected
• Abstinence intercourse
• IUD
• Implants
• Injectable depot medroxyprogesterone acetate SEXUALLY TRANSMITTED
• Contraceptive Patch DISEASE IN ADOLESCENTS
• Contraceptive pills (Progestin-only and com-
bined hormonal oral contraceptives) Neisseria gonorrhoeae
• Contraceptive vaginal ring
• Female condom Background
• Male condom • Most men are symptomatic
• Diaphragm—prevents pregnancy by acting as a • Female may present with PID
barrier to the passage of semen into the cervix
• Cervical cap—acts as a mechanical barrier to Clinical presentation in females
sperm migration into the cervical canal and as • Vaginal discharge
a chemical agent with the use of spermicide • Dysuria
• Spermicidal agent • Intermenstrual bleeding
• Lower abdominal pain: Most consistent
Absolute contraindication for combined hor- symptom of PID
monal oral contraceptive [11] • Right upper quadrant pain from perihepatitis
• Migraine with aura (Fitz-Hugh–Curtis syndrome)
• < 21 days postpartum
• Abnormal vaginal bleeding of unknown cause Clinical presentation in males
• Estrogen-dependent tumor • Burning upon urination and a serous dis-
• Liver disease charge; a few days later, the discharge usually
• Thromboembolic disease becomes more profuse, purulent, and some-
• Cerebral events times tinged with blood
• Hypertension (systolic > 160 or diastolic > 100) • Acute epididymitis
96 J. Addison
• Rectal infection: May present with pain, pru- • Gonococcal endocarditis is rare (more com-
ritus, discharge, or tenesmus mon in men than in women)
Disseminated gonococcal infection Diagnosis

• Arthritis dermatitis syndrome is the most • Nucleic acid amplification tests (NAATs) are
classic presentation highly sensitive and specific diagnostic tests
• Migratory polyarthralgia, especially of the for Chlamydia trachomatis and N. gonor-
knees, elbows, and more distal joints rhoeae infections and can be used with endo-
• Septic arthritis; the knee is the most common cervical, vaginal, urethral, and urine
site of purulent gonococcal arthritis specimens (Table 3.6)
• Skin rash (may involve the palms and
soles) Treatment [12]
• The dermatitis consists of lesions, varying • Uncomplicated gonorrhea
from maculopapular to pustular lesions, that –– Ceftriaxone 250 mg intramuscular (IM) as a
can be painful single dose and azithromycin 1 g orally as a
• Fever is common single dose (treatment for C. trachomatis)
Table 3.6 Differential diagnosis and treatment of genital ulcers

Syphilis Chancroid Lymphogranuloma venereum
Clinical findings
Treponema pallidum Haemophilus ducreyi Chlamydia trachomatis serovars
Chancre; painless ulcer palmar rash Painful genital ulcers Self-limited genital papules or
ulcers followed by painful inguinal
and/or femoral lymphadenopathy
Mucocutaneous lesions Tender, suppurative Commonly seen on coronal sulcus,
inguinal lymphadenopathy prepuce, glans, and scrotum
Lymphadenopathy. Cardiac, ophthalmic, auditory Posterior vaginal wall, vulva
abnormalities (gummatous lesions). Late latent syphilis
Diagnostic labs and evaluation
Dark-field examinations to detect T. pallidum No evidence of T. pallidum Clinical diagnosis based on
A diagnosis requires use of a nontreponemal (VDRL or infection by dark-field symptomatology and the exclusion
RPR) and a treponemal test (FTA-ABS] or TP-PA) examination of other etiologies
RPR or VDRL correlate with disease activity. A
fourfold change in titer is considered clinically
significant
CSF VDRL if neurosyphilis suspected Negative syphilis serologic
test
HSV PCR or HSV culture
is negative
Treatment
Primary, secondary, early latent: Azithromycin 1 g PO × 1 Doxycycline 100 mg PO BID for
Benzathine penicillin G 2.4 million units × 1 IM or 21 days
Alternative regimen only if nonpregnant and Ceftriaxone 250 mg IM × 1
penicillin allergy: or
Doxycycline 100 mg PO BID × 14 days Ciprofloxacin 500 mg PO
Late latent or latent of unknown duration: BID × 3 days Erythromycin base 500 mg PO
Benzathine penicillin G 2.4 million units IM q week for or QID for 21 days
latent syphilis Erythromycin base 500 mg
Neurosyphilis PO TID × 7 days
Aqueous crystalline penicillin G 3–4 million units IV
every 4 h × 10–14 days for neurosyphilis
RPR rapid plasma reagin, VDRL venereal disease research laboratory, FTA-ABS fluorescent treponemal antibody absorption test, CSF cerebrospi-
nal fluid, PO by mouth, HSV herpes simplex virus, IM intramuscular, BID twice a day, TID three times a day, QID four times a day
OR • Untreated cervicitis can progress to an

–– Doxycycline 100 mg orally twice daily for ascending genital tract infection (salpingo-
7 days oophoritis or PID)
• Disseminated gonococcal infection • C. trachomatis and N. gonorrhoeae are the
–– Ceftriaxone 1 gm intravenous (IV)/IM q most commonly associated organisms
24 h and azithromycin 1 g orally as a sin- • The highest rates of chlamydial/gonorrheal
gle dose infections occur among adolescent females
–– Cefotaxime 1 g IV q 8 h or ceftizoxime 2 g 14–24 years of age [13]
IV every 8 h for 7 days and azithromycin • Most infected individuals are asymptomatic,
1 g orally as a single dose especially females with chlamydial infections
• Other organisms can cause PID: Anaerobes,
Gardnerella vaginalis, Haemophilus influen-
Chlamydia trachomatis zae, Streptococcus agalactiae, Mycoplasma
hominis, Ureaplasma urealyticum, and
Men enteric Gram-negative rods
• Urethral discharge
• Asymptomatic infection is common Clinical presentation
• Absence of Gram-negative intracellular dip- • Abdominal pain
lococci in a urethral smear • Symptoms more intense during menses
• Presence of ≥ 5 WBCs/oil field is highly sen- • Abdominal tenderness (occasionally with
sitive and specific for urethritis rebound tenderness)
• Adnexal tenderness
Females • Cervical motion tenderness
• Mucopurulent cervicitis • Elevated temperature
• Often asymptomatic • Mucopurulent cervical discharge
• May have discharge or bleeding after
intercourse Diagnosis
• Definitive diagnosis by endometrial biopsy or
Diagnosis laparoscopy
• Nucleic acid amplification tests (NAATs)
Clinical diagnostic criteria
Treatment • At least one of the following:
• Azithromycin 1 g orally as a single dose or –– Cervical motion tenderness
doxycycline 100 mg orally twice daily for –– Uterine tenderness
7 days (in cases of azithromycin allergy) –– Adnexal tenderness
One or more of the following additional criteria

in conjunction with at least one minimum clini-
Pelvic Inflammatory Disease cal criterion can support diagnosis:
• Elevated WBC count
Background • Fever
• Most commonly due to untreated cervicitis • Elevated erythrocyte sedimentation rate or
• PID increases the risk of ectopic pregnancy; C-reactive protein concentration
infertility is a common complication of chla- • Mucopurulent cervical discharge
mydial infection • Cervical friability
98 J. Addison
• Evidence of positive gonococcal or chlamyd- • Strawberry cervix describes a diffuse or

ial infection patchy macular erythematous lesion of the
• Pelvic ultrasonography may demonstrate: cervix
–– Fluid in the cul-de-sac • Flagellated pyriform protozoa or trichomo-
–– Thickened fallopian tubes nads on saline wet mount is diagnostic
–– Tubo-ovarian abscess • Treatment should be instituted immediately
and, whenever possible, in conjunction with
Treatment [12] all sexual partners
• Outpatient treatment • Metronidazole and tinidazole are US Food
–– Ceftriaxone 250 mg IM × 1 plus and Drug Administration (FDA) approved
Doxycycline 100 mg orally twice daily × • Pregnant women with symptoms can be
14 days with or without Metronidazole 500 treated with metronidazole as well
mg orally twice daily for 14 days
• Inpatient
–– Cefoxitin 2 g IV every 6 hours plus dox- H uman Papillomavirus (HPV)
ycycline 100 mg orally twice daily for
14 days • HPV type 6 or 11 usually causes visible
or wart
–– IV clindamycin 900 mg IV every 8 hours • Besides the genital area, HPV type 6 or 11
plus gentamicin loading dose IV/IM can produce warts in conjunctival, nasal, oral,
loading dose (2 mg/kg), followed by a and laryngeal areas
maintenance dose (1.5 mg/kg) every 8 • HPV 16, 18, 31, 33, and 35 are associated
hours with cervical neoplasia, also neoplasm of
penis, anus, and vulva
• Treatment of external genital warts
Trichomoniasis –– Podofilox 0.5% solution or gel
–– Imiquimod 5% cream
• Trichomoniasis is due to the protozoa –– Cryotherapy
Trichomonas vaginalis (Table 3.7) –– Surgical removal
• Most men are asymptomatic • Note: C-section is not an indication because
• Most women will present with malodorous of genital warts; however, C-section may be
yellow-green thin and frothy discharge with indicated if the genital wart obstructs the pel-
vulvovaginal itching, burning, or soreness vic outlet
Table 3.7 Differential diagnosis of infections with vaginal discharge

Bacterial vaginosis Trichomoniasis Vulvovaginal candidiasis
Gardnerella vaginalis Trichomonas vaginalis Candida albicans
Homogenous, white, fishy odor, Malodorous yellow-green thin and Thin and watery, or thick and white
noninflammatory discharge that frothy discharge (like cottage cheese) discharge
smoothly covered the vaginal wall
Vulvar irritation is less common Vulvar itching, vulvar soreness and Vulvar itching, vulvar soreness and
irritation irritation
pH of vaginal fluid >4.5 pH of vaginal fluid >4.5 pH of vaginal fluid <4.5
Clue cells Flagellated pyriform protozoa Fungal cells
Metronidazole Metronidazole Antifungal topical cream or
fluconazole 150 mg oral tablet ×1
Human Immunodeficiency • Existing lice and nits can be seen in pubic

Virus (HIV) hair, on the body and on scalp
• Treatment is permethrin 1% topical liquid
Indication of HIV testing
• Routine screening once between 15 and

Scabies
18 years of age for all adolescents (https://
• Caused by Sarcoptes scabiei
www.aap.org/en-us/Documents/periodicity_
• Presents with intense itching
schedule.pdf)
• Burrows in the webs of the fingers and toes
• All who seek evaluation and treatment for
• Treatment is permethrin 5% cream
STDs
• Ivermectin 200 μ/kg orally, repeat in
• Adolescents with high-risk behaviors
2 weeks
• Unexplained enlargement of the parotid glands
• Adolescent with oral thrush
• Adolescent with acute retroviral syndrome; Vaccines Prevent STDs
fever, malaise, lymphadenopathy, and skin rash
• Hepatitis A
HIV testing –– Single IM dose of immunoglobulin after
exposure with a person with hepatitis A
• HIV-1 and HIV-2 antigen/antibody immuno-
infection (sexual contact or sharing IV
assay
drugs) if unvaccinated
• If there is suspicion for early infection in setting
–– Hepatitis A vaccine is recommended after
of an initial negative antigen/antibody immuno-
exposure
assay test, an HIV-1 nucleic acid test should be
• Hepatitis B
performed
–– Give hepatitis B immunoglobulin and hep-
atitis B vaccine after exposure (sexual
Herpes Simplex contact or sharing IV drugs) with a person
with hepatitis B if unvaccinated
• Genital herpes is HSV-2 – – Hepatitis B vaccination is recommended
• Painful itchy lesions with multiple vesicles • HPV
• Diagnosis: Isolation of HSV in cell culture is –– 9-valent human papillomavirus virus vac-
preferred, serology testing for herpes immu- cine (Gardasil- 9) protects against HPV
noglobulin G (IgG) type 6, 11, 16, 18, 31, 33, 45, 52, and 58
• Treatment: Acyclovir, famciclovir, valacyclovir – – Given in 3-dose series—0, 2, 6 months for
ages 15–26 years
–– Given in 2-dose series—0 and 6–12 months
Pediculosis after initial shot for ages 9–14 years
• Lice can be sexually transmitted and must

be included in the differential for an ado- PEARLS AND PITFALLS
lescent presenting with persistent pruritus
or nits • Always consider pregnancy in the differential
• Pediculosis usually presents with itching for an adolescent female with irregular or
• Phthirus pubis (crab louse) missed periods.
100 J. Addison
• When interviewing adolescents, perform a In: Rickert V, Joffe A, Gordon C, Callhan T,

history, physical exam, and psychosocial Katzman D, Neinstein L, editors. Neinstein’s
screening in a confidential manner. adolescent and young adult health care: a
• The American College of Obstetrics and practical guide. 6th ed. Philadelphia: Wolters
Gynecology recommends that cervical cytol- Kluwer; 2016. p. 38–41.
ogy not be obtained until the age of 21, 4. Boonstra H, Nash E. Special analysis. Minors and
regardless of age of sexual debut, number of the right to consent to health care. Guttmacher
lifetime partners, or history of sexually trans- Rep Public Policy. 2000;3(4):4–8. https://www.
mitted infection. Exceptions to this rule are guttmacher.org/sites/default/files/pdfs/pubs/
HIV-positive adolescents who should receive tgr/03/4/gr030404.pdf. Accessed 17 Nov 2018.
a cervical cytology test at the time of initial 5. Grossman DC, Curry SJ, Owens DK, et al.
diagnosis of HIV [14]. Screening for adolescent idiopathic sco-
• The majority of adolescent deaths are due to liosis. JAMA. 2018;319(2):165. https://doi.
unintentional injuries (motor vehicle acci- org/10.1001/jama.2017.19342.
dents), suicide, and homicide, which are often 6. Stager M. Substance abuse. In: Kliegman
associated with substance abuse. RM, Behrman RE, Schor NF, Stanton BF,
• Eating disorders are commonly thought to Geme JW, editors. Nelson textbook of pediat-
occur only in women. However, approxi- rics. 19th ed. Philadelphia: Saunders Elsevier;
mately one in three people struggling with an 2011. p. 671–85.
eating disorder is male. 7. Campbell K, Peebles R. Eating disorders
• Routine screening for STIs is important in children and adolescents: state of the art
because the majority of gonorrhea and chla- review. Pediatrics. 2014;134(3):582–92.
mydia infections are asymptomatic. 8. Fallat ME, Ignacio RC. Breast disorders in
children and adolescents. J Pediatr Adolesc
Acknowledgments The author gratefully Gynecol. 2008;21(6):311–6.
acknowledges the contribution of Marwa Abdou, 9. Klein DA, Poth MA. Amenorrhea: an approach
MD, Department of Pediatrics, Texas Tech to diagnosis and management. Am Fam
University Health Center, El Paso, Texas, USA, to Physician. 2013;87(11):781–8.
the 1st edition of this chapter, many of which have 10.
Emans SJ, Laufer MR. Emans, Laufer,
been incorporated into this edition as well. Goldstein’s pediatric and adolescent gynecol-
ogy. 6th ed. Philadelphia: Wolters Kluwer/
Lippincott Williams & Wilkins; 2012.
References 11. Curtis KM, Tepper NK, Jatlaoui TC, Berry-
Bibee E, Horton LG, Zapata LB, et al. U.S.
1. Marshall WA, Tanner JM. Variations in the medical eligibility criteria for contraceptive use,
pattern of pubertal changes in boys. Arch Dis 2016. MMWR Recomm Rep. 2016;65(3):1–
Child. 1970;45(239):13–23. 103. https://www.cdc.gov/mmwr/volumes/65/
2. Marshall WA, Tanner JM. Variations in pattern rr/rr6503a1.htm. Accessed 17 Nov 2018
of pubertal changes in girls. Arch Dis Child. 12. Centers for Disease Control and Prevention.
1969;44(235):291–303. Sexually transmitted diseases treatment
3. Sherer S, Radzik M. Psychosocial develop- guidelines, 2015. MMWR Recomm Rep.
ment in normal adolescents and young adults. 2015;64(RR-3):1–137. https://www.cdc.gov/
std/tg2015/tg-2015-print.pdf. Accessed 17 Suggested Reading

Nov 2018.
13. Centers for Disease Control and Prevention. American Psychiatric Association. Diagnostic
Sexually transmitted disease surveillance and statistical manual of mental disorders. 5th
2016. Atlanta: U.S. Department of Health ed. Washington, DC: American Psychiatric
and Human Services; 2017. https://www.cdc. Association; 2013.
gov/std/stats16/CDC_2016_STDS_Report- Rosen D, The Committee on Adolescence. Clinical
for508WebSep21_2017_1644.pdf. Accessed report-identification and management of eating
17 Nov 2018 disorders in children and adolescents. Pediatrics.
14.
Saslow D, Solomon D, Lawson HW, 2010;126:1240.
Killackey M, Kulasingam SL, Cain J, et al. Work Group on Eating Disorders. Practice guide-
American Cancer Society, American Society line for the treatment of patients with eating dis-
for Colposcopy and Cervical Pathology, and orders. 3rd ed. Arlington: American Psychiatric
American Society for Clinical Pathology Association; 2006.
screening guidelines for the prevention and Workowski KA, Bolan G. CDC sexually trans-
early detection of cervical cancer. CA Cancer J mitted diseases treatment guidelines, 2015.
Clin. 2012;62(3):147–72. MMWR Recomm Rep. 2015;64(3):1–140.
Genetic Disorders
4
Golder N. Wilson, Osama I. Naga, and Vijay S. Tonk
GENETICS AND Major anomalies

• Produced during organogenesis and involve
DYSMORPHOLOGY: single organs or regions (e.g., cleft palate,
BASIC FACTS congenital heart defects, hypospadias)
• Major anomaly combinations can represent a
Medical genetics syndrome, association, or sequence
• The human genome contains 6 billion A, G, –– Syndromes: Distinctive patterns of major
C, and T nucleotides in each diploid cell, and minor anomalies
packaged into 22 paired autosomes and 2 –– Associations: Mostly major anomalies
(XX or XY) sex chromosomes, totaling 46 conjoined more frequently than expected
chromosomes by chance
• Humans have ~23,000 genes, stretches of –– Sequences: Several anomalies arising from
DNA on chromosomes that encode RNA and a single embryogenetic defect
protein (1.5% of our genome) • Syndromes usually follow chromosomal or
Mendelian inheritance; single defects, multi-
Dysmorphology (dys = abnormal or painful)
factorial determination
• The study of birth defects (altered structure or
morphology) produced by abnormal Minor anomalies
embryogenesis • Distinguished from major anomalies by lack of
cosmetic or functional significance; produced
Teratology (terata = monstrosities)
during phenogenesis (e.g., hypertelorism/wide-
• Refers more specifically to anomalies pro-
spaced eyes, single palmar crease)
duced by physico-chemical agents during
• Minor anomalies distinguish syndromes from
pregnancy
single birth defects (isolated congenital
anomalies)
G. N. Wilson (*)
Department of Pediatrics, Texas Tech University Health Sciences
Chromosomal Inheritance
Center and KinderGenome Medical Genetics, Dallas, TX, USA
e-mail: golder.wilson@ttuhsc.edu Background
O. I. Naga • Normal chromosomal inheritance involves
Texas Tech University Health Sciences Center, El Paso, TX, USA the segregation of 22 plus X or Y chromo-
V. S. Tonk somes into gametes and their reunion in the
Department of Pediatrics, Texas Tech University Health Sciences fertilized egg as 46,XX or 46,XY zygotes
Center, Lubbock, TX, USA

104 G. N. Wilson et al.
• Abnormal chromosomal inheritance pro- A utosomal Dominant (AD)

duces extra (duplicated), missing (deleted), Inheritance
or rearranged (translocation) chromosomes in
gametes through abnormal meiotic division: Background
–– Extra or missing (unbalanced) chromo- • Every gene on the paired chromosomes 1–22
some material: Birth defects and intellec- (autosomes) has two copies or alleles, each
tual disability (ID) parent contributing one gene copy
–– Balanced rearrangements (e.g., transloca- • AD inheritance occurs when one gene copy
tions): Normal appearance with abnormal (allele) has a variant DNA sequence (muta-
gametes/offspring tion) that produces disease
• Dominantly inherited diseases have a 50%
Partial aneuploidies, microduplications, and chance that the abnormal allele will be passed
microdeletions [1] to each offspring
• Partial aneuploidy: Partial duplication or • Affected individuals have a 50% risk that
deletion of chromosome regions their disorder will recur in each offspring
• Extra or missing material can involve the (50%) recurrence risk
short (p) or long (q) chromosome arms
• Fluorescent in situ hybridization (FISH) and Usual characteristics of genetic transmission
microarray analysis define submicroscopic for AD diseases (Fig. 4.1)
(microdeletions) of 4p (Wolf-Hirschhorn) or • Both sexes are equally affected
7p (Williams) syndromes • Both sexes can transmit to offspring
• Microduplications of 11p (Beckwith- • No generation is skipped, producing a vertical
Wiedemann) or 7p (Williams) also cause pattern of affected individuals in pedigrees
syndromes • Every affected child has a parent with the
disorder
Translocations
• Translocations involve rearranged chromo- Exceptions to autosomal dominant inheritance
somes due to breakage and recombination • Variable or sex-limited expression, incom-
• Robertsonian translocations (end-to-end joining plete penetrance:
of short-armed chromosomes 13–15, 21–22) –– Variable expression (affected individuals
produce Patau or Down syndromes by transmit- have variable symptoms and severity)
ting attached 13 or 21 chromosome regions –– Incomplete penetrance (individuals with
• Reciprocal translocations (produced by the abnormal allele have no symptoms)
exchange of chromosome material) can
undergo unbalanced segregation, the extra/
missing material causing miscarriage or birth
defects in offspring
Ostensibly normal individuals

• A risk for non-disjunction in oocytes that
increases with age
• Ostensibly normal individuals may have
unrecognized chromosome mosaicism that
Fig. 4.1 Autosomal dominant pedigree. Note the square
passes abnormal chromosomes to offspring symbols for males, circles for females, connecting lines
(e.g., 46XX/45,X mosaicism producing 45,X between spouses and offspring, filled symbols for affected
Turner syndrome) individuals
4 Genetic Disorders 105
• New (de novo) mutations –– A 25% chance to have two normal copies
–– Affected offspring to unaffected parents (normal individual)
suggests a new mutation or germ-line –– A 50% chance to have one normal and one
mosaicism (below) abnormal copy (carrier individual)
• Germ-line mosaicism –– A 25% chance to have two abnormal alleles
–– Unaffected parents can have mutations in (affected individual)
germ-line cells (oogonia or spermatogonia)
–– Usual recurrence risks for unaffected par- Usual characteristics of genetic transmission in
ents with germ-line mosaicism are 5–10% AR cases (Fig. 4.2)
for each offspring • Males and females are equally affected
–– Affected children of these parents will • Males and females can each transmit copies
have the usual 50% recurrence risk for of the mutated gene
each offspring • Males and females affected with AR diseases
–– Germ-line mosaicism is more frequent in have mutations in both gene copies
certain AD disorders like osteogenesis • Males and females who have one copy of the
imperfecta mutant autosomal gene are called carriers
• Somatic mutations • Parents who have a previous affected child
–– Occur in a somatic cell and affect only that must be carriers
cell and its progeny • Parents who are both carriers have a risk of
–– Examples include segmental neurofibro- one-fourth or 25% for each offspring to be
matosis, skin, and other cancers affected
• All offspring of affected individuals will be
Examples of AD diseases carriers
• Osteogenesis imperfecta • Affected individuals can have affected off-
• Neurofibromatosis spring only if their spouse is also a carrier
• AD polycystic kidney disease • The chance for a spouse to have the same AR
• Achondroplasia disease is equal to twice the square root of
disease prevalence (per the Hardy-Weinberg
law)
Autosomal Recessive (AR) • The chance for a spouse to be a carrier
Inheritance increases greatly if the couple has common
ancestry
Background • Relatedness or consanguinity increases the
• AR inheritance occurs when an abnormal risk of having offspring with AR disorders
gene copy (allele) on an autosome recedes or
hides behind its normal partner, producing Exceptions to AR inheritance
disease only when both alleles are abnormal • Uniparental disomy
• Parents of children with AR disorders will –– Rare cases of AR disease can occur when a
typically have one normal and one abnormal carrier parent transmits both autosomes
gene copy, their single abnormal allele mak- containing the abnormal gene copy to a
ing them a “carrier” of disease rather than child
being affected by it – – The recurrence risk will then be negligi-
• Offspring will receive one or the other gene ble for future affected children rather than
copy such that they have: 25%
Fig. 4.2 Autosomal recessive pedigree with parental con- Fig. 4.3 X-linked recessive pedigree. Dots within symbols
sanguinity. Dots within symbols for carriers, filled symbols for carriers, filled symbols for affected individuals
for affected individuals
• X-linked dominant inheritance occurs when
• New mutation the abnormal X chromosome gene copy in
–– A new mutation altering the normal gene females dominates over its partner allele to
copy in an offspring receiving an abnormal cause disease
allele from a carrier parent may cause AR • X-linked dominant disorders are often lethal
disease in affected males because their only X chro-
–– The recurrence risk will then be negligible mosome allele is abnormal
for future affected children, rather than • X-linked dominant disorders can have odd
25% ratios of affected children due to miscarriage
of affected males
Examples of AR diseases
• Cystic fibrosis Usual characteristics of genetic transmission in
• Spinal muscular atrophies X-linked recessive cases (Fig. 4.3)
• AR polycystic kidney disease • Males are more commonly and more severely
• Diastrophic dwarfism affected than females
• Female carriers are generally unaffected or
affected more mildly than males
X-Linked Inheritance • Female carriers have equal chances to trans-
mit their normal or altered X chromosome,
Background
giving:
• Genes on the X chromosome are paired in
–– 25% risk for an affected son
XX females but mostly single (hemizygous)
–– 25% risk for a carrier daughter
in XY males
–– 25% chance for an unaffected son
• X-linked recessive inheritance occurs when
–– 25% chance for a non-carrier daughter
the single X chromosome gene copy of a male
• Affected males have:
is abnormal, most often when the mother is a
–– 100% chance each daughter will be a
carrier with one normal and one abnormal X
carrier
chromosome allele
–– 0% chance their sons will be affected
• Males with X-linked recessive disorders can
because their Y chromosome must be trans-
also occur through new mutation, comprising
mitted to sons
one-third of the first affected males in fami-
• Male-to-male transmission therefore excludes
lies according to Haldane’s law
X-linkage
• X-linked dominant diseases manifest in both –– Diagnosis of additional family members

sexes, with males being more severely indicates that additional genetic factors are
affected present with increased risk
• Example 2: Risk for parents with type I dia-
Examples of X-linked recessive diseases betes to have an affected child:
• Hemophilia A –– About 6% if only the father is affected
• Duchenne and Becker muscular dystrophy (atypical sex)
• Hunter syndrome –– About 4% if only the mother is affected
• Fabry disease (more commonly affected sex)
Examples of X-linked dominant diseases –– About 10–25% if both parents have type I
• X-linked hypophosphatemia diabetes (two affected primary relatives)
• Incontinentia pigmenti • Example 3: Risk for an average couple to
• Rett syndrome have a child with cleft palate:
• Most cases of Alport syndrome –– About 1 in 600 before having children
–– About 2–5% if their first child has cleft
palate (one relative with disease)
Multifactorial Determination –– About 10–12% if two children or a first
child and other relatives have clefts (more
Background
relatives affected)
• Multifactorial determination (not inheritance
–– Even higher if affected relatives have large
because environmental factors are involved)
bilateral clefts (more severe disease)
applies to common diseases like diabetes,
• Example 4: Risks for parents with a neural
coronary artery disease, asthma, and most
tube defect (spina bifida, anencephaly) to
isolated birth defects like cleft palate
have an affected child:
• Predisposition includes gene combinations
–– About 0.1% if neither parent is affected
(polygenic inheritance) and pre-/postnatal
(the general population prevalence depend-
environmental factors
ing on ethnicity)
• Risks for multifactorial diseases are empiri-
–– About 2% if mother is affected (typically
cal and approximate because all factors are
affected sex)
never defined
–– About 5% if father is affected (atypical
• Multifactorial determination often exhibits
sex)
sex predilection due to hormonal or other
–– Increased with low folic acid levels during
factors
pregnancy, the reason for routine folate
Multifactorial determination characteristics supplementation
• Example 1: Hip dysplasia is nine times more • Example 5: Risks for parents to have a child
common in females than in males with autism:
–– Unlike the fixed ratios of Mendelian inheri- –– About 1% (the general population
tance, recurrence risks for multifactorial prevalence)
disorders increase with –– About 5% for the next child if a son has
• The number of affected family autism (typically affected sex)
members –– About 10% for the next child if a daughter
• Affliction of the atypical sex has autism (atypical sex)
• Severity of the condition –– Increase with autism severity (e.g., autism
–– General recurrence risks for parents with a with ID versus high-functioning autism
first child affected are on the order of 3–5% spectrum disorder)
Mitochondrial Inheritance • Examples include disorders caused by

expanded triplet repeats such as fragile X
Background syndrome, Huntington chorea, and myotonic
• Mitochondria dystrophy
–– Have the only genetic material outside of
the nucleus
–– Are transmitted to zygotes only from eggs G enomic Imprinting
(Fig. 4.4) and not sperm (maternal inheritance)
–– Convert oxygen to biochemical energy Imprinting characteristics
(ATP) through four respiratory chain • Gene expression and clinical symptoms
complexes depend on whether the affected gene is trans-
• Mitochondrial diseases mitted from the mother or the father
–– Impact energy-dependent tissues: Brain, sen- • Uniparental disomy occurs if segments or
sory/peripheral nerves, muscle, heart, bowel entire copies of a chromosome come from
–– Are rarely transmitted by fathers since one parent rather than usual biparental
sperm have few mitochondria contribution
• Uniparental heterodisomy refers to inheri-
Examples of mitochondrial disease tance of both chromosome copies from one
• Leigh disease parent, while uniparental isodisomy refers to
• Kearns-Sayre syndrome inheritance of two copies of one parental
• LHON (Leber hereditary optic neuropathy) chromosome
• MELAS (mitochondrial encephalopathy with
stroke-like episodes and lactic acidosis) Examples of genomic imprinting
• MERRF (myoclonic epilepsy and red ragged • Prader-Willi syndrome and Angelman
fibers disease) syndrome
• Diagnosis of all cases can be achieved by
analysis of 15q11 DNA to define biparental
Genetic anticipation (normal result), maternal (Prader-Willi syn-
drome), or paternal (Angelman) methylation
• Genetic anticipation occurs when a disorder patterns
becomes more severe in subsequent
generations
Fig. 4.4 Pedigree of a mitochondrial disorder showing maternal inheritance

GENETIC TESTING [1] trisomy 21/Down syndrome, and 47,XXY for

a male with Klinefelter syndrome
Phenotypic Testing • Monosomies are similarly reported as 45,X
for usual Turner syndrome but are lethal
• A variety of anatomic and tissue traits were unless mosaicism (mixture of cells with nor-
observed including the Kayser-Fleischer mal and aberrant chromosomes) is present
rings in Wilson disease, the ragged red mus- • Mosaicism is reported using a slash, e.g.,
cle fibers in certain mitochondrial disorders, 46,XX/45,XX-21 for monosomy 21
and the excess liver glycogen in glycogen mosaicism
storage diseases • Translocations can involve reciprocal exchange
• Specific measurements and physical findings through breakage and exchange of two chro-
helped with genetic diagnosis, including: mosome regions (e.g., 46,XX,t[9q;22q])] or
–– Disproportionate short stature in joining of short-armed acrocentric chromo-
achondroplasia somes (e.g., 45,XY,t[14:21])
–– Extended wing span and long fingers in
Marfan syndrome
olecular Cytogenetics: Fluorescent
M
In Situ Hybridization (FISH)
Metabolic Testing
• Specific FISH tests involve use of differently
• As biochemical pathways were defined, colored test and control probes to highlight
chemical reactions were developed to mea- particular loci in chromosome spreads
sure abnormal levels of metabolites—e.g., • For example, a test red probe for the 22q11
the red/purple color of urine in those with region that gave a signal only on one of the
porphyrins two chromosomes 22 in metaphase spreads
• Chromatographic and then mass spectromet- would be diagnostic of the DiGeorge/
ric methods for defining excess metabolites velocardiofacial/22q11 deletion, provided the
were developed, focusing subsequent enzyme control green probe directed to the unaffected
and DNA analysis (see also Chap. 5 Metabolic 22 terminus gave signals on both chromo-
Disorders) somes 22 in all spreads
hromosome Analysis or
C NA Testing: Microarray Analysis
D
Karyotyping (aCGH or CMA)
• The chromosomes are examined for extra or • Examines every region of every chromosome
missing regions (bands) and aberrations and reports extra or missing DNA pieces
reported using specific nomenclature—chro- using coordinates established by the human
mosome number, sex chromosomes, p for genome project
short arm, q for long arm, and numbers for • Microarray analysis can find any chromo-
altered bands proceeding from the chromosome dosage alteration, from trisomies like
some center (centromere) 47,XX,+13 to small deletions like that of
• Entire extra chromosomes are reported as 22q11, but not balanced translocations that
47,XX,+13 for a female with trisomy 13/ involve rearrangement without duplication or
Patau syndrome, 47,XY,+21 for a male with deletion of DNA
DNA Testing: DNA Sequencing –– Risk for a chromosome disorder based on

family history
• Single gene sequencing: Delineates the –– Availability of tissue from postmortem or
nucleotide sequence of genes and defines biopsy that supports DNA analysis only
alterations (mutations) that cause disease. • Indications for a regular karyotype in addi-
Example: tion to microarray analysis are:
–– Diagnosis of sickle trait (one mutated beta- –– Normal individual with recurrent preg-
globin gene copy), normal, or sickle cell nancy loss, recognizing the possibility of a
individuals at the DNA level enabled pre- balanced translocation/rearrangement
natal testing using fetal tissues –– Patients with extra chromosome material
• Gene panel sequencing: Sequencing of mul- that could derive from trisomy or transloca-
tiple genes associated with a type of disease tion, such as 46,XX,t(14;21) translocation
Example: versus 47,XX,+21 Down syndrome—
–– Sequencing of > 40 genes known to cause microarray will only detect the extra 21
epilepsy or > 20 known to cause material, not whether it is present as trans-
cardiomyopathy location or free-standing chromosome 21
• Genome sequencing (genomics): Sequencing –– Individuals with multiple CNVs (copy
of all human genes or DNA. Example: number variations) or indeterminate results
–– Whole exome sequencing (WES) looks at by microarray that suggest complex chro-
protein-coding regions (exons of genes), mosome rearrangements or mosaicism
focusing on DNA variants that cause rather • Indications for DNA testing based on
than associate with disease (e.g., mutations symptoms:
causing sickle cell or CF) –– Suspicion of a Mendelian disorder based
–– Together, microarray and genomic on symptoms or family history (including
sequencing constitute a new approach suspected inborn errors of metabolism
called genomics, where the genetic focus where DNA testing can replace enzyme or
on one gene is expanded to the entire metabolite analysis)
genome –– Presence of a diagnostic category (e.g.,
epilepsy) that has gene panel testing
–– Physician or patient preference for genome
linical Applications of Genetic
C sequencing to detect symptom-related and
Testing (Table 4.1) other detrimental mutations
Postnatal genetic testing based on symptoms Presymptomatic genetic testing

• Traditional medical testing is guided by clini- • Test for genetic diseases and predispositions
cal symptoms and the resulting differential before symptoms
diagnosis • Complex consent is required
• Indications for chromosome testing, now • May affect potential employment or cause
using microarray analysis as a first line test, insurance discrimination
include: • Example:
–– Symptoms like ID or autism –– Presymptomatic diagnosis of Huntington
–– Dysmorphology and/or multiple clinical chorea in a young person with its predic-
anomalies, particularly with growth delays tion of middle-age dementia may cause
–– History of recurrent pregnancy loss depression and suicidal ideation
Table 4.1 Summary of genetic testing strategies

Strategy Sample Genetic test
Newborn—abnormal metabolic screen
Follow-up screen Blood spot Confirm altered metabolite
Definitive diagnosis Blood/cheek swab Enzyme/DNA to confirm inborn
error
Future screen Cheek swab WES for all Mendelian diseases
Newborn—specific chromosome disorder suspected
Rapid screen Blood Rapid FISH for trisomies 13, 18,
21, monosomy X
Definitive Dx Blood Routine karyotype and microarray
analysis
Newborn with heart defect like tetralogy of Fallot
Rapid screen Blood FISH for deletion 22a
Definitive Dx Blood Routine karyotype and microarray
analysis
Child with delays, autistic behaviors
PE—normal male Blood Microarray, fragile X DNA
analysis
PE—normal female Blood Microarray analysis
PE—specific syndrome Blood/cheek swab Targeted DNA test or panel (e.g.,
for Noonan syndrome)
PE—birth defects, dysmorphology Blood/cheek swab Routine karyotype and microarray
analysisb
Pregnancy, child with family history, age, or other risks for genetic disorder (e.g., abnormal fetal ultrasound)
Parent carrier testing Blood Routine karyotype if child has
translocation
Targeted DNA test for known
disorder (e.g., CF)
Presymptomatic Dx Blood Targeted DNA test for at-risk
disorder (e.g., fragile X)
Prenatal Dx: PGD Embryonic cells Targeted DNA test on embryos
obtained by IVF
Prenatal Dx: NIPT Fetal cells in maternal blood DNA dosage screens for common
trisomiesc
Prenatal Dx: CVS/amniocentesis Chorion/amnion cells Routine karyotype, FISH for
deletion 22, targeted DNA test
Individuals or pregnancies with no genetic risks
Genomic screening Blood, embryonic, fetal samples Combined whole exome
sequencing and microarray
analysis to detection any genetic
diseasec
CF cystic fibrosis, CVS chorionic villus sampling, Dx diagnosis, FISH fluorescence in situ hybridization, IVF in vitro fertil-
ization, NIPT noninterventional prenatal testing, PE physical exam, PGD preimplantation genetic diagnosis, WES whole
exome sequencing
a
Some recommend microarray analysis for any child with a heart defect
b
Increasing use of whole exome sequencing as first-line test since improved technology defines DNA dosage as well as
sequence change
c
Future detection of all chromosome or Mendelian disorders is feasible but not yet practical
Genetic screening Prenatal diagnosis based on maternal blood

• Universal newborn metabolic screening has screening
improved clinical outcomes • Combination of fetal ultrasonography, mater-
• Screening particular ethnic groups, e.g.: nal blood and serum testing, and invasive
–– Cystic fibrosis (CF) in Caucasians sampling of fetal cells for genetic testing
–– Sickle cell anemia in African-Americans • Measures the levels of fetal proteins like
–– Several disorders like Tay-Sachs among alpha-fetoprotein in maternal serum (MSAFP)
people of eastern European (Ashkenazi) and/or amniotic fluid (amniotic AFP)
Jewish descent • Clinical significance
–– Elevated levels of MSAFP indicate leakage
Preconception screening of fetal fluid into the amniotic cavity
• Preconception counseling through birth defects like anencephaly/
–– Crucial for pregnancy risks and maternal- spina bifida, gastroschisis/ruptured ompha-
child health locele, or urologic disorders causing fetal
–– Ability to screen over 200 disorders is now proteinuria
available –– Low levels of MSAFP indicate lower fetal
–– Example weight and growth delay, common in chro-
◦◦ Women over 35 with increased risks for mosome disorders like trisomy 13/18 and
chromosome disorders somewhat in trisomy 21
Preimplantation genetic diagnosis (PGD)

• Used for in vitro fertilization (IVF) for those T
raditional Prenatal Diagnosis
with infertility
• Single cells are removed from the resulting Amniocentesis
embryos to determine presence of normal or • Needle aspiration of amniotic fluid at
abnormal chromosomes or genes 12–16 weeks of pregnancy
• Detection of single embryonic cells with • Less than 0.1% risk for miscarriage when
mutant alleles before implantation performed with ultrasound guidance to avoid
fetal tissue damage
Noninvasive pregnancy testing (NIPT) • Amniotic fluid can be used to measure levels
• Uses fetal cells that enter the maternal blood- of fetal proteins like AFP or maternofetal hor-
stream early in pregnancy mones as in the triple test on maternal serum
• DNA from these cells can be distinguished
from maternal DNA when there are chromo- Chorionic villus sampling (CVS)
some aberrations such as the extra chromo- • Earlier diagnosis in pregnancy
some 21 in Down syndrome • Using catheters to aspirate cells from the fetal
• Detection of fetal Down syndrome and other portion of the early placenta (chorion) at
trisomies can be achieved in maternal blood 10–12 weeks of pregnancy
samples as early as 10 weeks of pregnancy • CVS has higher risks for miscarriage (1–2%)
• NIPT currently has significant error rates, so than amniocentesis
abnormal results should be confirmed by • Traditional prenatal diagnosis by CVS or mid-
standard prenatal diagnosis [2] trimester amniocentesis can be performed
only with specific diagnosis in mind, e.g., a • If trisomy 21 is found by microarray analysis,
prior child with phenylketonuria or Down a routine karyotype must be performed to dis-
syndrome rather than nonspecific ID tinguish trisomy (e.g., 47,XY,+21) from
translocation (e.g., 46,XY,t[14:21])
Indications for prenatal diagnosis are: • Finding a translocation mandates testing of
• Prior child with chromosome aberration the parents to decide if it was inherited or
• Maternal age over 35, the risk of common tri- arose de novo
somies like Down syndrome reaching about • Robertsonian translocations that join two
1% compared to less than 1 in 1000 before short-armed or acrocentric chromosomes
age 30 (chromosomes 13–15, 21–22) to form one
• Parent with translocation that confers signifi- chromosome occurs in 3.3% of cases
cant risks for fetal trisomy • Mosaicism, e.g., 46,XX/47,XX,+21, also
• Recurrent pregnancy loss with no obvious requires a karyotype and occurs in 2.4% of
cause or parental genetic disorder may justify cases
low-risk amniocentesis in a premium • Risks for a first affect child with trisomy 21 are
pregnancy 1 in 1500 for mothers aged 15–29, 1 in 800 for
ages 30–34, 1 in 270 for ages 35–39, 1 in 100
for ages 40–44, and 1 in 50 for over 45
EXAMPLES OF CHROMOSOME • Parental recurrence risk for trisomy 21 after
DISORDERS: AUTOSOMAL birth of an affected child is 1% plus the mater-
ANEUPLOIDIES nal age-related risk
• Risk of recurrence in Robertsonian
Examples of syndromes and associations are pre- translocation
sented with sections comprising Background –– If the mother is a 14:21 translocation car-
(describing prevalence, diagnostic tests, inheri- rier (45,XX,t[14:21]), her recurrence risk
tance), Abnormalities (major and minor if war- is 15% for translocation Down syndrome
ranted), and Health Supervision/Preventive Care at mid-pregnancy (by amniocentesis) and
(for more common disorders). Data for these 10% at birth
entries are taken from textbooks [3, 4], specific –– If the mother has a 21;21 translocation, her
references as listed, and information available to recurrence risk approaches 100%
all at specific sites [5] or the general Internet. • Median survival increased from 25 to
49 years, cardiac defects mainly responsible
• Dementia and Alzheimer disease are more
Down Syndrome (Fig. 4.5) common and of earlier onset in adults with
Down syndrome
Background
• Prevalence of 1 in 660 newborns with tri- Clinical findings in the newborn
somy 21 nondisjunction (comprising 94% of • Flat facial profile
cases) • Hypotonia—poor Moro reflex, parachute
• Similar prevalence in males, females, and in sign
different ethnic groups relative to maternal • Flat occiput/brachycephaly
age • Excess skin, back of the neck
• Microarray analysis or routine karyotype will • Upslanting palpebral fissures (see Fig. 4.5)
show extra material from chromosome 21 • Small and anomalous auricles
Fig. 4.5 (a) Upslanting a

palpebral fissures,
epicanthal folds
consistent with trisomy
21 Down syndrome in a
1-year-old girl; (b)
47,XY,+21: Abnormal
male karyotype with
trisomy 21, consistent
with Down syndrome
1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18
19 20 21 22 X Y
Major abnormalities • Vision and hearing deficits: Hearing loss,

• Development: ID—IQ range 25–50 with middle ear fluid
occasional individuals above 50; social per- • Dental: Tooth anomalies, periodontal disease
formance averages 3–4 years over mental • Cardiac (40–50%): Endocardial cushion
age; most children friendly, musical, trea- (atrioventricular septal) defects are most
sured by families common
• Growth: Short stature with frequent failure to • Respiratory: Obstructive sleep apnea, fre-
thrive quent infections
• Neural: Microcephaly, atlanto-axial • Skin: Keratosis/dry skin, pustules, and
instability cellulitis
• Eye: Hyperopia/astigmatism, strabismus, • Gastrointestinal (GI) defects: duodenal atre-
blepharitis sia, Hirschsprung anomaly, celiac disease
• Ear: Small canals, chronic otitis, (look for classic double bubble sign indicating
cholesteatoma duodenal atresia on abdominal radiograph)
• Thyroid: Hypothyroidism, usually acquired Investigations

with high thyroid-stimulating hormone (TSH) • Cord blood karyotype for confirmation if
• Genital: Cryptorchidism diagnosed prenatally, microarray analysis if
• Hematology: Leukemoid reactions, transient routine in locale, routine blood karyotype to
myeloproliferative disorder (TMD), polycy- distinguish trisomy from translocation if
themia; TMD regresses but confers a 10–30% microarray shows excess 21 material
risk for later leukemia (1% risk overall for • Brainstem auditory evoked response or oto-
Down syndrome) acoustic emission hearing screen at birth
• Echocardiography after birth even if no
Minor anomalies—nonspecific but useful for murmur
diagnosis • Thyroid function testing in the newborn
• Brachycephaly/flat occiput period with state newborn screens, repeated
• Central placement of the posterior hair whorl at 6 months, 12 months, and yearly thereafter;
• Upslanting palpebral fissures endocrine referral if abnormal (watch for
• Flat midface high TSH with normal T4)
• Full cheeks • Monitor neonatal jaundice, obtain complete
• Epicanthal folds blood count and differential at birth to evalu-
• Speckled iris (Brushfield spots) ate for myeloproliferative disorders and poly-
• High arched palate cythemia; continue monitoring for signs of
• Absent to very small nipple buds leukemia; check hemoglobin level annually
• Single palmar creases (40%) starting at 1 year of age to screen for iron
• Hypoplasia of fifth finger middle phalanx deficiency anemia
causing clinodactyly (50%) • Obtain a radiographic swallowing assessment
• Wide (sandal) gap between great and second for infants with slow feeding, choking with
toes (50%) feeds, recurrent pneumonia, or other recur-
rent or persistent respiratory symptoms and
Health supervision and preventive care [6] unexplained failure to thrive
• Sleep study at age 1 year to exclude obstruc-
Counseling
tive apnea due to narrow airway and
• Initial supportive counseling outlining suspi-
hypotonia
cion of diagnosis and associated medical
• Celiac screening at age 2 years or with
problems, ideally to alert mother with spouse
symptoms
or support person present
• Cervical flexion-extension radiographs by
• Informative counseling when chromosome
3–5 years, when planning to participate in
studies are returned, emphasizing modern
contact sports or if neck pain, torticollis, gait
improved prognosis with better healthcare,
disturbance, or weakness
positive adjustment by most families (visit by
experienced parent if possible) Referrals
• Early childhood intervention (ECI) and local
Examination
Down syndrome group
• Complete physical examination from head to
• Speech and occupational therapy to support
toe
breastfeeding because of oromotor hypoto-
• Rectal and abdominal examination at birth;
nia, reflux, and constipation
monitor for reflux, constipation, other GI
defects
• Eye evaluation at birth for red reflex and cata- • Associated anomalies can mimic those of
ract; ophthalmology referral before age VACTERL syndrome
6 months and then annually to screen for stra-
bismus and other eye disorders Major abnormalities
• Ear-nose-throat/otolaryngology (ENT), refer- • Altered gestational timing, 1 in 3 premature
ral at 6 months and 1 in 3 postmature
• Audiology if speech abnormally delayed • Development: Severe ID with most unable to
• Pulmonologist to assess for airway anomalies walk or communicate verbally beyond single
if stridor, wheezing, noisy breathing words; many will smile, laugh, and interact
• Hematology oncology if TMD and with their families
polycythemia • Growth: Intrauterine growth retardation,
• Endocrine referral if abnormal severe postnatal deficiency
• Neural: Microcephaly, hypertonia, absent
General corpus callosum, spina bifida
• If constipation is present, evaluate for • Apneic episodes, poor feeding, marked fail-
restricted diet or limited fluid intake, hypoto- ure to thrive with cleft lip/cleft palate in 6%
nia, hypothyroidism, or GI tract malforma- • Eye, skeletal, vertebral, limb, cardiac, renal,
tion/stenosis and genital defects are common
• Parents of infants with TMD should be coun-
seled regarding the risk of leukemia and made Minor anomalies—nonspecific but useful for
aware of the signs, including easy bruising, diagnosis
petechiae, onset of lethargy, or change in • High forehead, prominent occiput
feeding patterns • Redundant neck skin
• Atlantoaxial subluxation or instability at each • Short sternum
visit by history and physical exam • Clenched fist, overlapping fingers with hypo-
• Physical therapy and exercise are extremely plastic nails and dermal pads
important and postpone dementia in adults • Ulnar deviation of hands (club hands)
• Car safety seat evaluation for infants before • Rocker bottom feet
hospital discharge due to risks for postural • Hypoplastic muscle and adipose tissue
apnea, bradycardia, or oxygen desaturation
from hypotonia, neck flexibility—increased
risk after cardiac surgery Trisomy 13 (Patau Syndrome)
• Immunizations—all routine immunizations (Figs. 4.7 and 4.8)
should be given
Background
• Prevalence 1 in 5000 newborns, similar by
Trisomy 18 (Edwards Syndrome) sex and ethnicity
(Fig. 4.6) • The least common and most severe of the
viable autosomal trisomies
Background • Risk of recurrence in future pregnancies for
• Second most common trisomy among live trisomy 13 is less than 1%
born children • Death by 1 month (82%), median survival
• Recurrence risks for trisomy 18 are less 7 days, death often from central apnea due to
than 1% provided a translocation is not brain anomalies
involved
• 50% die in the 1st week, 90–95% in the 1st Major abnormalities
year, median survival 14.5 days, death often • Development: Severe ID—no walking or
from central apnea speech; react to touch, tickling, voices
Fig. 4.6 (a) Small face a

relative to head size,
arched eyebrows, narrow
palpebral fissures
consistent with trisomy
18 Edwards syndrome;
(b) 47,XY,+18: Abnormal
male karyotype with
trisomy 18, consistent
with Edwards syndrome
1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18
19 20 21 22 X Y
• Growth: Intrauterine growth retardation,

severe postnatal deficiency
• Neural: Microcephaly, hypertonia, holopros-
encephaly, spina bifida, sensorineural deaf-
ness, blindness
• Apneic episodes, poor feeding, failure to
thrive, cleft lip/palate in 50–60%
• Eye, ear, skeletal, cardiac, GI, renal, genital
defects are common
Minor anomalies—nonspecific but useful for

diagnosis
• Scalp defect, wide sutures, sloping forehead
Fig. 4.7 Cleft lip and palate, postaxial polydactyly consis-
• Redundant neck skin
tent with trisomy 13 Patau syndrome • Small eyes, hypotelorism
Fig. 4.8 47,XY,+13:
Abnormal male
karyotype with trisomy
13, consistent with Patau
syndrome
1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18
19 20 21 22 X Y
• Clenched fist, sometimes overlapping fingers • Routine karyotype or microarray analysis

as in trisomy 18 will show a 47,XXY karyotype with more
• Hyperconvex fingernails, hypoplastic toenails severe variants that have additional X and Y
• Rocker bottom feet as with trisomy 18 chromosomes (48,XXXY, 48,XXYY,
49,XXXXY)
Health supervision and preventive care for tri- • Individuals with 47,XXY/46,XY mosaicism
somy 18 and Patau have better prognosis for fertility
• Cord blood karyotype for confirmation if
diagnosed prenatally, microarray analysis if Neurobehavioral abnormalities
routine in locale, routine blood karyotype • Learning differences: IQ ranges between 85
(see Fig. 4.8) to distinguish trisomy from and 90 with better verbal performance
translocation if microarray shows excess 13 • Academic difficulties with problems in
or 18 material expressive language, auditory processing,
• Initial and informative counseling, ideally and memory
involving a multidisciplinary care team expe- • Behavior problems include immaturity, shy-
rienced in discussing poor prognosis and pal- ness, poor self-esteem, and social and peer-
liative care interaction difficulties
• Fatigue and weakness with less goal-directed
thinking and self-motivation
EXAMPLES OF CHROMOSOME • Intention tremor
DISORDERS: SEX
Physical and medical abnormalities
CHROMOSOME ANEUPLOIDIES • Growth: Tall stature with asthenic build and
long limbs (low upper to lower segment ratio)
Klinefelter Syndrome (Fig. 4.9) • Gynecomastia with increased risk for male
breast cancer (20 times that of healthy men)
Background
• Hypogonadism with hypogenitalism, small
• Klinefelter syndrome is the most common
penis and testes, extragonadal germ cell cancers
chromosomal disorder associated with male
• Infertility with azoospermia, small, firm testes
hypogonadism and infertility
Fig. 4.9 47,XXY:
Abnormal karyotype with
an extra X sex-
chromosome, consistent
with Klinefelter
syndrome
1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18
19 20 21 22 X Y
• Low serum testosterone levels • Microarray analysis or routine karyotype will

• High luteinizing hormone (LH), follicle stim- show the extra Y chromosome material
ulating hormone (FSH), and estradiol levels • Despite theoretical XY and Y gametes, risk
• Delayed secondary sexual characteristics, for XYY offspring is very low
subnormal libido, erectile dysfunction, • Tall stature is not evident until they are
• Eye: Coloboma, strabismus, corneal opacity 5–6 years old
• Cardiac: Aortic stenosis, mitral valve prolapse
• Connective tissue: Scoliosis when young, Physical and medical abnormalities
pectus excavatum, inguinal hernias • Development: IQ is often normal, rang-
• Skeleton: Radioulnar synostosis, genu recur- ing between 80 and 140 with early speech
vatum, osteoporosis delay
• Autoimmune problems such as diabetes have • Behavior problems include distractibility,
increased incidence hyperactivity, and temper tantrums, but the
publicized aggression is often controlled by
Health supervision and preventive care adolescence
• Early suspicion of the diagnosis allows tes- • Tall stature with acceleration in mid-child-
tosterone therapy for those with hood, increased length versus breadth, and
insufficiency large hands and feet
• Ophthalmology, cardiology, and endocrinol- • Other skeletal and genital defects may occur
ogy referrals
• Discussion of reproductive options
• Monitoring for breast cancer in adulthood
Turner Syndrome
Background
XYY Syndrome • Prevalence: 1 in 2000 live-born female infants
compared to about 1 in 40 conceptuses
Background
• 15% of pregnancies end in spontaneous abor-
• XYY syndrome is often recognized during
tions and 15% of those have Turner syndrome
evaluation for behavior differences
• Distinctive phenotype mostly due to missing hypothyroidism), diabetes with carbohydrate

genes on the X short arm intolerance, tendency for obesity
• Most patients have a 45,X karyotype (two-
thirds are missing the X from their father) Health supervision and preventive care [7]
• Other karyotypes e.g., 45,X/46,XY mosa- • Cord blood karyotype for confirmation if
icism leading to gonadoblastoma diagnosed prenatally, microarray analysis if
• Girls with amenorrhea and absent breast routine in locale, routine blood karyotype (see
development by age 13 and those with unex- Fig. 4.11) to distinguish 45,X from variants
plained short stature should have microarray and detect 45,X/46,XX mosaicism with better
analysis followed by karyotyping (Fig. 4.11) prognosis for reproduction and 45,X/46,XY
• Deletion of the SHOX gene produces the sim- mosaicism with risks for gonadoblastoma
ilar Leri-Weill dyschondrosteosis short stat- • Abdominal ultrasound
ure syndrome with Madelung deformity of • Newborn hearing screen and audiology
the wrist monitoring
• Thyroid functions, including TSH at age
Neonatal findings 1 year and every 1–2 years
• Decreased birth length and weight (average • Endocrine referral at age 2 if thyroid function
2900 g) normal—for monitoring and discussion of
• Congenital lymphedema with puffiness over growth and other hormonal supplementation
dorsa of fingers and toes that has been shown to increase adult stature
• Low posterior hairline with webbing of neck (see also Chap. 12 Endocrinology)
(Fig. 4.10) (pterygium colli), reflecting pro-
nounced fetal lymphedema
• Often heralded prenatally by lymphedema
• Broad chest with widely spaced nipples
• Narrow, hyperconvex, or deeply set nails
• Pedal edema
Abnormalities
• Development: Mild learning difficulties with
average IQ 90
• Growth: Short stature beginning at birth and
continuing to adulthood
• Neural: Visual-spatial and fine motor deficits,
clumsiness, perceptive hearing impairment
• Genital: Ovarian dysgenesis and failure (sus-
pect in girls with no breast development/
amenorrhea at ages 12–14
• Other: Anomalous ears, chronic otitis, stra-
bismus, cardiac defects (bicuspid aortic valve,
coarctation of the aorta with hypertension,
later aortic root dilation), horseshoe kidney
• Elevated levels of LH and FSH confirm ovar-
ian failure and prognosis for infertility
• Pubic hair development is normal
Fig. 4.10 Female infant with webbed neck and low poste-
• Increased risk for autoimmune disorders— rior hairline due to lymphedema consistent with Turner
Hashimoto thyroiditis (up to 30% develop syndrome
Fig. 4.11 45,X: Abnormal

karyotype with one X sex
chromosome, consistent
with Turner syndrome
1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18
19 20 21 22 X Y
• Cardiac monitoring for aortic dilatation dur- • Growth: Tall stature with smaller head size
ing teen and adult years (20th percentile average) and narrow shoul-
• Reproductive genetic referral to evaluate der girdle
uterine thickness and prognosis for fertility • Facies: Not dramatically unusual with mid-
and pregnancy face hypoplasia, epicanthal folds,
• Long-term hormonal treatment: See Chap. 12 taurodontism
Endocrinology • Skeletal: Fifth finger clinodactyly, radioulnar
synostosis
• Genital: Normal puberty, variable or absent
Triple X (XXX) Syndrome menses, normal or reduced fertility
Background
• Routine karyotype needed to quantify fre- EXAMPLES OF CHROMOSOME
quent mosaicism (46,XX/47,XXX)
• Risk for 47,XXX or 47,XXY offspring is
DISORDERS: PARTIAL
1–5% ANEUPLOIDIES
• Rare cases with additional X chromosomes
occur (e.g., 48, XXX, 49, XXXX), women W olf-Hirschhorn Syndrome (Fig. 4.12)
with 49,XXXX resembling Down syndrome
Chromosome 4 short/p arm deletion (4p-)
Abnormalities
• Development: Delays particularly in Background
speech with IQ range 30–80, average of • Prevalence: 1 in 20,000–50,000 births
55; 60% require special education in high • Deletion of the chromosome 4 short arm (4p-)
school demonstrated by routine karyotype or micro-
array analysis
Health supervision and preventive care

• Newborn: Hearing screen with subsequent
audiology, cardiology evaluation
• Infancy: Early childhood intervention, oph-
thalmology, renal ultrasound, neurology/
electroencephalogram (EEG), feeding and
swallowing monitoring
Cri-du-Chat Syndrome
Chromosome 5 short/p arm deletion (5p-)
Background
• Prevalence: 1 in 20,000–50,000 births
• Deletion of the chromosome 5 short arm (5p-)
can be demonstrated by routine karyotype or
microarray analysis
Abnormalities
• Mewing cry in infants (may be due to laxity
or abnormalities in the larynx)
• Development: Severe ID—some affected
Fig. 4.12 Hypertelorism with prominent brow and broad children attain developmental ages of
nasal root typical of Wolf-Hirschhorn syndrome 5–6 years and half have adequate communi-
cation for basic needs
Abnormalities • Growth: Low birth weight (72% less than
• Development: Severe ID in patients with 2.5 kg), failure to thrive, short stature
larger deletions—40% become ambulatory, • Neural: Microcephaly, hypotonia
10% toilet-trained, and 90% have seizures • Face: Unusual appearance with round face,
• Growth: Severe deficiency, failure to thrive, hypertelorism, epicanthal folds, flat nasal
feeding problems often needing gastrostomy bridge, down-slanting palpebral fissures, low-
• Neural: Feeble fetal activity, postnatal hypoto- set and/or malformed ears
nia, microcephaly, absent septum pellucidum • Eye, cardiac, skeletal, and genitourinary
• Face: Unusual appearance that in extremes defects
resembles a Greek warrior helmet with its mid-
line metal prong—the prominent forehead and Health supervision and preventive care
nasal root/glabella highlight this appearance • Newborn: Hearing screen with subsequent
• Face: Ocular hypertelorism, beaked nose, audiology, cardiology evaluation
“carp”-like mouth with down-turned corners, • Later monitoring of feeding, growth, hearing,
cleft lip vision; check for skeletal changes
• Eye, ear, cardiac, and skeletal anomalies
De Grouchy Syndrome Major abnormalities

• Development: Moderate ID, IQ range 41–80
Chromosome 18 long (q) arm deletion (18q-) with mean of 56, higher language than cogni-
tive ability; those with microduplication more
Background severe with higher incidence of autism
• Deletion of the chromosome 18 long arm • Behavior: Strikingly friendly and loquacious
(18q-) demonstrated by routine karyotype or personality, anxiety, hyperactivity
microarray analysis • Growth: Mild prenatal growth deficiency,
postnatal deficiency around 75% of normal,
Abnormalities early feeding problems with colic and consti-
• Development: Moderate ID with IQ ranging pation often cause early failure to thrive
from 40 to 85; visual and hearing problems • Neural: Microcephaly, early hypertonia and
may worsen cognitive prognosis mild spasticity, poor coordination, and motor
• Growth: Normal birth weight with short stat- function
ure (lower segment hypoplasia), growth hor- • Eye and ear defects, typical supravalvular
mone deficiency aortic or pulmonic stenosis, early hypercalce-
• Neural: Microcephaly, hypotonia, hydro- mia in 67% can lead to renal failure
cephalus, porencephaly, cerebellar • Connective tissue changes include enamel
hypoplasia hypoplasia, kyphosis, pectus excavatum,
• Face: Unusual appearance with midface inguinal hernias, joint laxity and contractures,
hypoplasia, deep-set and small eyes, down- and lax skin
turned corners of the mouth, elevated lower
lip, high palate, cleft palate (30%), malformed Minor anomalies—nonspecific but useful for
ears with small canals diagnosis
• Eye, cardiac, genitourinary defects with low • Distinctive and recognizable facial appear-
IgA and thyroid dysfunction ance (Fig. 4.13)
• Coarse or elfin facies due to early periorbital
fullness that can mimic a storage disease
EXAMPLES OF CHROMOSOME • Stellate pattern of the iris
DISORDERS: MICRODELETIONS • Anteverted nares with long philtrum
• Prominent lips
Williams Syndrome
Health supervision and preventive care [8]
Microdeletion or microduplication of band • Neonatal hearing screen, cardiology and oph-
7q11.23 thalmology consults, renal functions and
ultrasound, calcium and electrolyte levels,
Background early childhood intervention, and optimistic
• Prevalence: 1 in 10,000 births, the majority counsel
with 7q11.23 microdeletion • Monitor growth, feeding, bowel function,
• Submicroscopic deletion or duplication of calcium levels, renal functions, hearing, and
chromosome band 7q11.23 can be demon- vision in childhood
strated by targeted FISH or, more generally, • Screening for autistic behaviors, particularly
by microarray analysis in microduplication cases; developmental
• Parental FISH studies should be considered if pediatrician for behavior and school
symptoms present difficulties
• Eye: Aniridia in most, congenital cataracts,

nystagmus, vision loss
• Urogenital: Cryptorchidism, hypospadias
• Tumors: Wilms tumor, gonadoblastoma

• Patients with aniridia should have FISH for
the WAGR deletion to ascertain risks for
Wilms tumor
• Monitoring for Wilms tumor is controversial;
one recommendation is to screen when the
risk is over 5% [9]
• Wilms tumor monitoring is clearly indi-
cated for WAGR patients; renal sonography
every 4 months up to age 7 years suggested
for disorders with strong genetic predispo-
sition [9]
Alagille Syndrome
Background
• Prevalence: Rare—around 200 cases reported
Fig. 4.13 Coarse “elfin” facies of Williams syndrome with • Microarray analysis will show microdeletion
stellate irides and prominent lips of the 20p12 region containing the JAG1 gene
in 7%
• Mutations in the JAG1 gene account for 70%
Wilms Tumor-Aniridia-Growth Delay-
of cases
Retardation (WAGR) Syndrome • Both microdeletion and mutation cases fol-
low autosomal dominant inheritance with a
Background
50% recurrence risk for affected patients
• Prevalence: Rare—around 70 cases reported
• Prognosis depends on severity of cholestasis
• Microarray analysis or targeted FISH shows a
and cardiac disease, survival to age 20 in 75%
microdeletion on the short (p) arm of chro-
for all patients, 60% in those requiring liver
mosome 11 (11p13-)
transplantation
• Correlates with the two-hit model of carcino-
genesis, the WAGR microdeletion being the Abnormalities
first hit present in all tissues with a second • Development: Mild ID in 16%
“hit” (WT1 gene mutation) within developing • Growth: Short stature, occasional hypothy-
urogenital tissue producing Wilms tumor roidism or growth hormone deficiency
• Face: Typical and recognizable—triangular
Abnormalities
face, broad forehead, long nose with flat tip,
• Growth/development: Moderate to severe ID
prominent and pointed chin, hypodontia, low-
with short stature
set and/or malformed pinnae, inner ear anom-
• Face: Prominent lips, small jaw, ear anomalies
alies with hearing loss
• Eye: Posterior embryotoxon affecting cornea

and anterior chamber angle, Axenfeld anomaly
• Cardiac defects (peripheral pulmonary steno-
sis or tetralogy of Fallot), renal and skeletal
defects
• GI problems: Cholestasis with elevated serum
bile acids within first 3 months, in 100% by
age 3 years
DiGeorge or Velocardiofacial
Syndrome: Microdeletion 22q11.2
(Fig. 4.14)
Background
• Prevalence: 1 in 10,000 births
• Targeted FISH or more generally microarray
analysis will show microdeletion of 22q11.2
• Targeted FISH for 22q11.2 microdeletion
often performed routinely on patients with
tetralogy of Fallot
• Variable clinical expression ranging from Fig. 4.14 Narrow palpebral fissures and smaller jaw typical
neonatal problems (DiGeorge presentation) of velocardiofacial syndrome (DiGeorge)
to palatal/speech defects (Shprintzen/velo-
cardiofacial presentation) to behavioral dif- • Eye (cataracts) and cardiac defects (ventricu-
ferences similar to schizophrenia lar septal defect [VSD], tetralogy of Fallot),
• Patients with the microdeletion have a 50% parathyroid agenesis with hypocalcemia, thy-
risk of transmission mic aplasia with hypothyroidism and immune
• Palatal cleft/dysfunction, mandibular hypo- deficiency, urogenital defects (ureteral reflux,
plasia, parathyroid, thymic, and cardiac hypospadias)
defects represent abnormal branchial arch
development Minor anomalies
• Some but not all have a characteristic facial
Major abnormalities appearance
• Development: ID (40%), IQ range 55–78 • Narrow palpebral fissures, prominent nose,
with higher verbal performance malar hypoplasia
• Behavior: Impulsive behavior, bland affect, • Micrognathia sometimes severe enough to
phobias, psychosis in some cause Robin sequence
• Growth: Failure to thrive with dysphagia and
reflux, short stature Health supervision and preventive care
• Neural: Microcephaly, seizures, obstructive • Cord or neonatal blood for microarray analy-
sleep apnea (50% of neonates), hearing loss sis if pre- or postnatal diagnosis by FISH—
• Face: Narrow choanae, cleft palate, submu- deletions can vary in size, and clinical
cous cleft, velar paresis, hypotonic pharynx, prognosis correlates with particular deleted
Robin sequence regions
• Neonatal hearing screen, renal sonogram, • Sleep disorders: Daytime somnolence, snor-
chest radiograph to view thymus ing, restless sleep, cataplexy, sleep apnea
• ENT, cardiology, and appropriate cleft palate • Face: Thick and scanty saliva, dental maloc-
team involvement clusion, increased dental caries, poor enamel
• Monitoring of feeding, growth, immune, thy- • Eye (strabismus), and skeletal (kyphoscolio-
roid, and renal function sis, club foot) defects
• Genital: Hypogonadotropic hypogonadism—
small labia-clitoris or penis-scrotum, cryptor-
EXAMPLES OF CHROMOSOME chidism (80%), precocious puberty, early
DISORDERS-MICRODELETIONS adrenarche, amenorrhea (60%), or delayed
menses (as late as 28 years)
WITH IMPRINTING • Endocrine: Hypothalamic dysfunction,
growth hormone deficiency, diabetes, insulin
Prader-Willi Syndrome (PWS)
requirement
Background
Minor anomalies
• Bitemporal hollowing due to hypotonia with
• The loss of paternally imprinted genomic
narrow bifrontal diameter
material at the 15q11.2q13 locus results in
• Light hair and eye color with frontal upsweep
Prader-Labhart-Willi syndrome (PWS)
of scalp hair
• Absence of the 15q11q13 band by high-reso-
• Almond shape of palpebral fissures, down-
lution chromosome analysis, the 70% of cases
turned corners of the mouth (Fig. 4.15)
that have microdeletions can be diagnosed by
• Narrow, small hands with straight ulnar
targeted FISH or microarray analysis
border
• Reduced life expectancy if morbid obesity
• Hypogonadism may be subtle
occurs
Major abnormalities
• Cord or neonatal blood for karyotype and
• Diminished fetal activity leading to severe
microarray analysis if pre- or postnatal diag-
neonatal hypotonia
nosis by FISH or DNA methylation analysis
• Development: ID is mild in 63%, moderate in
• Neonatal hearing screen, feeding evaluation
31% and severe in the rest; 75% require spe-
by specialists, apnea and sleep assessment
cial education at some point with decreased
• Early childhood intervention, ophthalmology,
reading (12-year level) and math (9-year
and endocrine referral—growth hormone
level) skills
therapy is beneficial but has a small risk of
• Behavior: Obsessive eating and hyperphagia
death in the few months after initiation of
due to lack of satiety sensation in hypothala-
treatment
mus, cheerful with periods of rage and stub-
bornness, interest in puzzles, bizarre foraging
and eating, skin picking ngelman Syndrome
A
• Growth: Early failure to thrive due to oromo-
tor dysfunction, short stature with small Background
hands and feet, morbid obesity if hyperphagia • The loss of maternally imprinted genomic
not strictly controlled material at the 15q11.2q13 locus results in
• Neural: Microcephaly, poor fine and gross Angelman syndrome (AS)
motor coordination, high pain threshold, • Absence of the 15q11q13 band by high-reso-
hypernasal speech, temperature instability lution chromosome analysis, the 70% of cases
• Behavior: Paroxysmal laughter, sometimes

associated with gelastic seizures (epilepsy
with bursts of energy like laughing or crying),
related to brainstem defects rather than hap-
piness or humor
• Neural: Microbrachycephaly, hypotonia, sei-
zures, self-mutilation, sleep issues, puppet-
like gait (ataxia with jerky arm movements)
that with the laughter led to the pejorative
term “happy puppet syndrome”
• Face: Large mouth and prominent jaw due to
posturing, tongue protrusion, drooling, and
eye defects
EXAMPLES OF MENDELIAN
SYNDROMES: ID AND SUBTLE
DYSMORPHOLOGY
Fragile X Syndrome [10]
Background
• X-linked inheritance
• Isolation of DNA from the Xq28 fragile site
showed unusual structure with a series of tri-
nucleotide repeats near the transcription ini-
Fig. 4.15 Broad nasal root and down-turned corners of tiation site of what became known as the
mouth indicating prenatal hypotonia in Prader-Willi fragile X mental retardation-1 or FMR1 gene
syndrome
• Affected males had dramatic expansion in the
range of 400–1000 triplet repeats, accounting
that have microdeletions can be diagnosed by for the microscopically visible fragile site,
targeted FISH or microarray analysis while fathers who transmitted an unstable X
• In contrast to PWS, only 2% of AS cases to their daughters had 60–100 repeats (repeat
result from inheriting two copies of the pater- expansions of 60–200 repeats in males and
nal chromosome 15 (uniparental disomy) and females are called premutations)
require DNA methylation analysis to show • Mild expansion of the triplet repeats as seen
absence of the maternal methyl-group in premutation males leads to additional
(imprinting) pattern instability with some slight further expansion
in their carrier daughters
Abnormalities • Premutations in carrier females undergo dra-
• Development: Severe ID, absent speech or matic expansion during female meiosis,
fewer than 6 words, most toilet-trained by explaining the generational worsening of
day and some at night; all incapable of inde- symptoms (genetic anticipation) seen in frag-
pendent living ile X syndrome
Major abnormalities • The presence of a Turner-like appearance

• Development: Usually severe ID in males gave rise to the term “male Turner syndrome,”
with IQ ranging from 30 to 55; some milder erroneous because the condition has equal
exceptions especially in females with higher sex distribution
repeat values (IQ less than 70 in 30–50%)
• Behavior: Hyperkinetic/autistic/aggressive Major abnormalities
behaviors; anxiety in females • Findings are based on patients with the
• Neural: Early hypotonia, seizures with abnor- clinical diagnosis and may vary when
mal EEG, cluttered speech, stuttering genetic testing defines specific subtypes—
• Connective tissue dysplasia leading to eye see those disorders for refined complication
(strabismus), cardiac (mitral valve prolapse, risks [3]
aortic dilation), and skeletal (scoliosis, flat • Development: Mild ID (IQ range 64–127,
feet) defects with joint and skin laxity median 102), speech differences
• Genital: Macro-orchidism, premature ovarian • Behavior: Stubbornness, mood disorders,
failure in symptomatic females rare autistic manifestations
• Growth: Frequent failure to thrive, feeding
Minor anomalies difficulties, later proportionate and mild short
• Proportionate macrocephaly stature (50%)
• Long and narrow face (60%) • Neural: Motor delays, vision deficits, hearing
• High palate with prominent jaw (usually after loss (usually conductive)
puberty) • Connective tissue dysplasia: Scoliosis, pectus
• Large, flexible ears with decreased cartilage (upper carinatum, lower excavatum), joint
• Testicular enlargement may be subtle laxity, lax skin, bleeding diathesis
• Eye (strabismus), cardiac (pulmonic stenosis,
Health supervision and preventive care [10] septal defects, hypertrophic cardiomyopa-
• Neurologic, developmental, and genetic thy), urogenital (obstructive uropathy, crypt-
referrals when diagnosis made orchidism) defects
• Cardiac and behavioral monitoring • Lymphatic: Pulmonary lymphangiectasia,
chylothorax, non-immune hydrops
• Tumors: Pheochromocytoma, ganglioneu-
EXAMPLES OF MENDELIAN roma, juvenile myelomonocytic leukemia
SYNDROMES: MILD ID (often with PTPN11 gene rearrangements/
AND PROPORTIONATE amplification
GROWTH DELAY Minor anomalies
• Short, webbed neck (Fig. 4.16)
Noonan Syndrome • Low posterior hairline
• Ptosis, down-slanting palpebral fissures
Background
• Low-set or abnormal pinna (“jug-handle”
• Prevalence 1 in 1000–2500
ears)
• DNA testing for several mutations in the
• Cubitus valgus, single palmar creases
RAS-MAPK signaling pathway will show
• Edema of the hands and feet
mutations responsible for Noonan syndrome
• Gene panels are available, 50% have muta- Health supervision and preventive care
tions in the tyrosine phosphatase (PTPN11) • Neonatal hearing screen, renal sonogram,
gene on chromosome 12 ophthalmology, cardiology referrals
some cases of type IV exhibiting autosomal

dominant inheritance
• The condition involves abnormal neural crest
development, accounting for pigmentary
changes and, in some cases, Hirschsprung
disease
Abnormalities
• Development: Mild cognitive delays that can
be related to the hearing loss
• Neural: Sensorineural hearing loss, nonprogres-
sive, unilateral or bilateral, due to hypoplasia of
structures in the organ of Corti and semicircular
canals (evident on head computed tomography)
• Eye: Iris pigmentary abnormality—hetero-
chromia (eyes of different colors), bicolored
iris, pale blue eyes with hypoplastic iridic
stroma, hypopigmented fundus, peripheral
retinal pigmentation
• Hair: Hypopigmentation with poliosis (white
forelock), white hairs on other body regions,
premature graying
• Face: Medial flare of bushy eyebrows, dysto-
pia canthorum (lateral displacement of inner
Fig. 4.16 Short webbed neck of an infant with Noonan canthi), high and broad nasal bridge with
syndrome
hypoplastic alae nasae
• Cardiac, skeletal, and urogenital defects
• Monitor thyroid, renal functions; regular car-
occur in some
diac monitoring for aortic and valve changes
• Cervical spine radiographs before sports, Health supervision and preventive care
anesthesia • ENT and audiology team after diagnosis,
deaf community and physician team discus-
sion of cochlear implant and hearing aid
EXAMPLES OF MENDELIAN options
SYNDROMES: CRANIOFACIAL • Alertness for symptoms of cardiac, skeletal,
DEFECTS AS MAJOR FINDING and GI defects
Waardenburg Syndrome
Treacher Collins Syndrome
Background
• Prevalence: About 1 in 40–50,000 births, hav- Background
ing a 1.4% incidence in congenitally deaf • Prevalence: 1 in 50,000 births
children • Targeted DNA testing or whole exome
• Like Noonan syndrome, an array of different sequencing will show a mutation in the trea-
gene mutations (PAX3, MITF, EDN3, etc.) cle (TCOF1) gene in the chromosome
and subtypes have been described, all except 5q31.3q32 region
• Autosomal dominant inheritance pattern with –– Anterior plagiocephaly: Early fusion of

50% transmission risk in affected individuals one coronal suture, unilateral flattening of
• Most severe cases are new mutations the forehead
• Confusion with the low genetic risk Goldenhar –– Posterior plagiocephaly: Early closure of
syndrome/association may also occur if eye one lambdoid suture
and malar changes are not dramatic –– Brachycephaly: Early bilateral coronal
suture fusion
Abnormalities –– Trigonocephaly: Early fusion of metopic
• Development: ID (5%), usually normal unless sutures, keel-shaped forehead and
compromised by unrecognized hearing loss hypotelorism
• Growth: Early failure to thrive because of –– Turricephaly: Early fusion of coronal,
feeding difficulties, airway abnormalities sphenofrontal, and frontoethmoidal
• Neural: Conductive deafness due to ear sutures, cone-shaped head
anomalies –– Clover-leaf skull or Kleeblattschädel
• Craniofacial: Mandibulofacial dysostosis with anomaly
underdeveloped mandibular and zygomatic • Syndromes involving craniosynostosis (coro-
bones causing small jaw and malar hypopla- nal synostosis most common, but any suture
sia, projection of scalp hair onto lateral cheek can be involved)
• ENT: Choanal atresia, pharyngeal hypoplasia –– Apert syndrome: Craniosynostosis, hand
with macro- or microstomia, cleft palate, syndactyly
external and middle ear anomalies with canal –– Crouzon syndrome: Craniosynostosis, no
stenosis and ear tags limb defects
–– Pfeiffer syndrome: Craniosynostosis,
broad thumb and toes
Craniosynostosis Syndromes –– Saethre-Chotzen syndrome: Craniosynos-
tosis, often asymmetrical, brachydactyly
Background
and syndactyly
• Prevalence: 4–6 per 10,000 births if primary
–– Carpenter syndrome: Tower or clover-leaf
and secondary synostosis are included; cra-
skull due to multiple fused sutures, preax-
niosynostosis syndromes range from 1 in
ial polydactyly, obesity
25,000 (Saethre-Chotzen) to 1 in 100,000
• All syndromes but Carpenter (autosomal reces-
births (Apert) or rarer
sive) exhibit autosomal dominant inheritance.
• Craniosynostosis refers to premature fusion
• Isolated craniosynostosis, like other single
of cranial sutures, often causing abnormal
birth defects, exhibits multifactorial determi-
head shape
nation with 3–5% recurrence risk
• Can have primary (ossification defect) or sec-
• Mutations in specific genes have been defined
ondary causes (failure of brain growth, rickets)
for the major syndromes, often in fibroblast
• Occurs as an isolated defect or as part of over
growth factor receptor (FGFR) genes
90 syndromes
• Specific gene testing or gene panels can pro-
• Types of craniosynostosis
vide a molecular diagnosis with options for
–– Scaphocephaly: Early fusion of sagittal
prenatal diagnosis in subsequent
sutures, long and narrow head shape
pregnancies
Abnormalities a craniofacial team to prevent cognitive and

• Development: Surgical release of craniosyn- sensory deficits
ostosis can prevent ID, but IQ often in 70–74 • Craniofacial surgery team evaluation, includ-
range ing neurosurgery, ophthalmology, ENT, and
• Neural: Restriction of brain growth, increased cleft palate expertise
intracranial pressure causes ID, visual, and • Monitoring of hearing, vision, and develop-
hearing defects ment is critical in the more severe
• Cranial: Abnormal shape as discussed for syndromes
various suture fusions above
• Plagiocephaly occurs with asymmetric syn-
ostosis; mild cases due to uterine constraint EXAMPLES OF
must be distinguished MENDELIAN DISORDERS
• Face: Midface hypoplasia, palatal clefts, jaw
changes
WITH DISPROPORTIONATE
• Early airway obstruction may require GROWTH DELAY (DWARFISM)
tracheostomy
• Eye: Shallow orbits, exophthalmos/ocular A chondroplasia (Fig. 4.17)
proptosis, exposure keratitis due to sphenoi-
Background
dal synostosis
• Cervical vertebral, cardiac, and limb defects
• Achondroplasia is the most common type of
often occur
short limb dwarfism, involving rhizomelic
• Types of limb defects rather than the involved
hypoplasia
suture(s) guide craniosynostosis syndrome
• Skeletal radiologic survey to define affected
diagnosis
bone regions can tailor the differential of
Health supervision and preventive care skeletal dysplasia, often suggesting the diag-
• Most craniosynostosis conditions are evident nosis of achondroplasia by its typical spine
at birth and require immediate involvement of and hip changes
Fig. 4.17 General
manifestations of Prominent forehead
achondroplasia
normal sized head
very short arm
trident hand
normal sized trunk (increased distance
between ring and middle
finger)
very short thigh

• Specific mutation in fibroblast growth factor • Somatosensory potentials to measure trans-

receptor 3 (FGFR3) gene on chromosome mission through foramen magnum, and check
• Other mutations in this gene cause severe for cord compression
thanatophoric dwarfism or milder hypo
• Flexion-extension radiography to assess cer-
chondroplasia vical instability/respiratory obstruction
• Autosomal dominant inheritance with a 50% • Management controversies include use of
recurrence risk for affected individuals decompressive surgery for cervical cord com-
• More than 80% of patients are due to new pression, limb- lengthening procedures, and
mutations growth hormone therapy as many have poor
response
Abnormalities
• Lifespan: Sudden infant death in 5% and
depression common EXAMPLES OF MENDELIAN
• Development: Normal if complications like DISORDERS WITH LAX
hearing loss or cervical cord compression are
prevented, motor milestones often lag by CONNECTIVE TISSUE
3–6 months because of macrocephaly and (CONNECTIVE TISSUE
early hypotonia DYSPLASIAS)
• Growth: Short stature with males averaging
130 cm (~4 ft-2) and females 123 cm (4 ft) arfan Syndrome (Figs. 4.18, 4.19,
M
• Neural: Altered cerebrospinal fluid (CSF) cir- and 4.20)
culation, cord compression, conductive and
sensorineural hearing loss Background
• Cranial: Macrocephaly, platybasia, narrow • Prevalence is 1 in 1000–2500
foramen magnum, maxillary hypoplasia • Marfan syndrome is one of many disorders
• Face: Frontal bossing, myopia, shallow nasal grouped by McKusick as heritable disorders
bridge, myopia, chronic otitis media of connective tissue
• Respiratory issues: Due to small chest, upper • Criteria developed for clinical diagnosis are
airway obstruction, and sleep-disordered less important now that targeted DNA testing
breathing will demonstrate mutations in the fibrillin-1
• Skeleton: Rhizomelic limbs causing extra (FBN1) gene on chromosome 15
skin folds, cervical spine fusion, • Practical clinical criteria involve one major
kyphoscoliosis, joint laxity leading to finding (eye or heart) along with several
arthritis and injuries, splayed fingers (trident minor findings listed below (e.g., Marfanoid
hands) habitus, arachnodactyly maneuvers, skin
• Genital: Uterine fibroids, menorrhagia, nar- changes)
row pelvis requiring cesarean delivery • Marfan syndrome exhibits autosomal domi-
nant inheritance with an equal sex ratio and
Health supervision and preventive care variable expression
• Monitor for feeding difficulties and apnea
• Infantile respiratory and sleep evaluations, Abnormalities
anesthesia precautions • Lifespan: The major cause of death is aortic
• Childhood ophthalmology, ENT, and ortho- dissection, preventable by beta-blocker or
pedic follow-up losartan therapy
lax joint
chest wall deformity
long arm
long fingers
flat foot
Fig. 4.19 General manifestations of Marfan syndrome
Fig. 4.18 A child with Marfan syndrome, showing the frag-

ile and aged face with pectus excavatum
Fig. 4.20 Thumb and

wrist signs in Marfan
syndrome
• Development: Normal with occasional verbal • 20% of women, 10% of men are hypermobile
performance discrepancy and visual attention defined by scores > 4–5 on the 9-point
problems Beighton scale [12]
• Growth: Tall stature, low upper to lower seg- • Early recognition of hypermobility can guide
ment ratio, thin and fragile habitus activities that prevent adolescent injury and
• Neural: Dural ectasia, sacral meningocele, early arthritis
anterior or posterior disc herniation • Diagnosis allows treatment of associated
• Cranial: Dolichocephaly, prominent supraor- autonomic imbalance (tachycardia, chronic
bital ridges, temporomandibular joint disease fatigue, bowel issues)
• Eye defects: Ectopia lentis, myopia, retinal • Associated autonomic imbalance (dysauto-
detachment nomia) leads to treatable postural orthostatic
• Cardiac: Aortic enlargement, mitral valve tachycardia (POTS), low bowel motility/irri-
dysfunction and prolapse, arrhythmias, aneu- table bowel syndrome (IBS), and mast cell
rysms of the aorta or pulmonary artery activation disorder (MCAD)
• Pulmonary: Reduced vital capacity, sponta- • Nonspecific diagnoses like fibromyalgia,
neous pneumothorax emphysema chronic fatigue syndrome, and serum-nega-
• Skeletal: Scoliosis, spondylolisthesis, flat tive rheumatoid arthritis are often due to EDS
feet, joint laxity with dysautonomia
• Arachnodactyly: Evidenced by ability to per- • Diagnostic criteria less important in era of
form the Walker-Murdoch (overlap of genomic testing, but a practical approach
thumb—5th finger when encircling the wrist; could include:
see Fig. 4.20) and Steinberg (protruding –– For classical or hypermobile EDS:
thumb beyond ulnar hand border with ◦◦ Major criteria: Joint hypermobility and
clenched fist) signs skin elasticity/scarring
• Epidermal: Atrophic striae (stretch marks), ◦◦ Minor criteria: Smooth/velvety skin and
recurrent incisional hernias joint subluxation/injury
• Hematologic: Clotting tendencies, renal vein –– For vascular EDS:
thrombosis ◦◦ Major criteria of typical “tight, chiseled
face,” arterial aneurysm/dissection and/
Health supervision and preventive care [11] or bowel rupture
• Cardiology and ophthalmology evaluations ◦◦ Minor criteria of translucent skin, mus-
when diagnosis suspected cle/joint rupture
• Monitoring of aortic root size at intervals dic-
tated by symptom severity (6 months to Abnormalities
3–4 years), often accompanied by beta- • Lifespan: Generally normal with the excep-
blockers or losartan therapy tion of vascular EDS
• Activity and physical therapy to strengthen mus- • Development: Early motor delays, normal
cles with frequent prohibition of collision sports cognitive function, anxiety, depression from
chronic pain
• Growth: Early colic and failure to thrive due
Ehlers-Danlos Syndrome (EDS) to low bowel motility/IBS; eosinophilic
esophagitis (MCAD)
Background • Central nervous system: Migraines, chronic
• Prevalence: Listed as 1 in 5000 births for all daily headaches, Chiari deformation, fragile
types but much more common if patients with dura contributing to CSF leaks
more subtle joint laxity/hypermobility and • Peripheral nerves: Carpal-tunnel syndrome,
skin elasticity are included chronic regional pain syndromes

• Usual diagnosis as teen or young adult—car-
diology, orthopedic, GI, allergy/mast cell
referrals with monitoring for joint pain/injury,
tachycardia, fatigue, anxiety, constipation/
diarrhea, reflux, allergy, skin reactivity
• Evaluate for head and neck pain, especially
posterior, and consider upright head magnetic
resonance imaging (MRI) study for Chiari
• Encourage swimming and light weight lifting
rather than running
• POTS treated with hydration, salt, high pro-
tein diet, medications (beta-blockers, mido-
drine, fludrocortisone)
• Mast cell activation treated by allergists with
antihistamine protocols (triple-drug therapy:
cetirizine/ranitidine/montelukast)
Osteogenesis Imperfecta
Fig. 4.21 Marked skin extensibility in a patient with Ehlers-
Danlos syndrome Background
• Prevalence: 1 in 20,000 births if all types are
• Joints: Hypermobile with subluxations, liga- included
ment/tendon tears, osteoarthritis, plica bands, • Four major types are recognized with cranio-
areas of dead bone facial changes, deafness, bowed limbs, and
• Skin: Elastic, thin and translucent, easy bruis- fractures—type II is an outlier with lethal
ing, striae, white-surfaced and keloid scars, dwarfing limb and chest changes
slow healing (Fig. 4.21) • Heterozygous mutations in the genes for the
• Face: Distinctive only in some with vascular alpha-1 and alpha-2 chains of collagen I
EDS—bulging eyes, thin nose and lips due to (COL1A1, COL1A2)
tight skin • Autosomal dominant inheritance patterns
• Eye (myopia, retinal detachment); mouth • Targeted COL1 gene testing will provide the
(dental, temporomandibular joint [TMJ] diagnosis in over 80% of cases
issues); GI (IBS, low motility); cardiovascu-
lar (tachycardia, valvular prolapse, aneu- The four types of osteogenesis imperfecta
rysm); skeletal (kyphoscoliosis, flat feet, (Sillence classification):
herniated disc) defects • Type I: Near normal growth with blue-gray
• Allergy/pulmonary: Frequent asthma/short- sclerae, multiple fractures, and later hearing loss
ness of breath, food and medication intoler- • Type II: Extremely severe with usual death in
ances, transient rashes/hives, anaphylaxis, the perinatal period and rare survival for
spontaneous pneumothorax months; poorly mineralized cranium and long
• Urogenital: Pelvic congestion with menor- bones with large fontanel, hydrocephalus,
rhagia, endometriosis, ovarian cysts; hyper- hypotonia, short and bowed limbs distorted
active bladder with increased urinary tract by multiple fractures in utero and callus
infections, bladder and uterine prolapse formation
a b
Fig. 4.22 Blue sclera in a 23-day old female infant and her mother who have type I osteogenesis imperfecta
• Type III: Prenatal growth deficiency, multiple • Vitamin D and calcium supplementation if
fractures at birth, limb bowing, severe kypho- hypophosphatasia with large fontanel, frac-
scoliosis leading to respiratory compromise; tures, and similar dental problems is excluded
dentinogenesis imperfecta is severe, bluish
sclerae less after infancy
• Type IV: Short stature with limb deformities; EXAMPLES OF
femoral bowing in infancy that improves; MENDELIAN DISORDERS
dental changes
• Other types have been added, including a
WITH OVERGROWTH
type VI with vertebral fractures and lack of (GIGANTISM)
COL1 mutations
Beckwith-Wiedemann Syndrome
Abnormalities are listed for the most common (BWS)
type I as a prototype
• Development: Usually normal since hearing Background
loss occurs late (third decade) • Prevalence: 1 in 12,000 births and probably
• Growth: Prenatal deficiency and short stature higher, with some cases having only
with significant limb fractures macroglossia
• Neural: Hearing impairment due to otosclerosis • Caused by deletion, gene mutations, or altered
• Cranial: Macrocephaly, Wormian bones, mal- imprinting of the 11p15 region
occlusion of jaw • Usually sporadic with low recurrence risk but
• Face: Blue-gray sclera, dentin/pulp hypopla- some cases are autosomal dominant
sia, translucent blue-gray teeth, caries • Insulin-like growth factor-2 is up-regulated in
(Fig. 4.22) the paternal chromosome 11 and suppressed
• Fractures (92% overall): 8% at birth, 23% by genes on the maternal chromosome 11, so
infancy, 45% preschool, 17% school, less maternal translocation/deletion or paternal
after puberty duplication/uniparental disomy (20%) are
• Connective tissue: Lower limb bowing, more common causes of BWS
kyphoscoliosis, easy bruising, inguinal and
umbilical hernias Abnormalities
• Lifespan: Infant mortality is significant (20%)
Health supervision and preventive care due to hypoglycemia, polycythemia, respira-
• Neonatal skeletal radiologic survey to ascer- tory problems
tain fractures and extent of deformities • Development: Occasional mild/moderate ID,
• Orthopedic care with later hearing screening perhaps from early hypoglycemia
• Endocrine consultation may help with • Growth: Large birth weight (average 4 kg),
bisphosphonate therapy tall stature at 95th percentile through adoles-
cence, weight 75th–95th percentile, macroso-

mia with large muscles and thick subcutaneous
tissue, organomegaly, hemihypertrophy
• Craniofacial: Large fontanels, metopic ridge,
nevus flammeus on forehead and eyelids,
posterior ear pits/creases, macroglossia inter-
fering with respiration and feeding
• Endocrine: Hypoglycemia responsive to ste-
roid therapy resolving by 1–4 months
• Cardiac (septal defects, tetralogy of Fallot);
GI (omphalocele, umbilical hernia); genito-
urinary defects
• Skeletal: Advanced bone age, hemihyperpla-
sia of limbs, polydactyly (4%)
• Tumors: Abdominal (4–7.5%), including
Wilms, hepatoblastoma, gonadoblastoma,
adrenocortical carcinoma

• Neonatal attention to hypoglycemia, respira-
tory obstruction, feeding
• Prone positioning as with Robin sequence
may aid respiration
• Macroglossia can persist through early
childhood
• Tumor monitoring using renal sonography
and serum alpha-fetoprotein levels every Fig. 4.23 Macrocephaly in a child with Sotos syndrome
4 months up to age 7 years [9]
• Growth: Large birth size (mean weight 3.9 kg,

OTOS SYNDROME (CEREBRAL
S length 55.2 cm), increased growth velocity
GIGANTISM) with increased bone age and stature persist-
ing over 97th percentile with ultimate height
Background in upper-normal range
• Prevalence: 1 in 20,000–30,000 births • Neural: Macrocephaly (Fig. 4.23), seizures,
• Targeted testing for mutation or deletion (rare dilation of cerebral ventricles, early hypoto-
except in Japanese) of the NSD1 gene at 5q35 nia/poor feeding (40% tube-fed)
is diagnostic • Face: Characteristics with prominent fore-
• Autosomal dominant inheritance with most head, triangular shape, down-slanting palpe-
cases representing new mutations bral fissures, pointed chin
• Eye (strabismus), ear (otitis with conductive
Abnormalities hearing loss), mouth (high palate, worn teeth)
• Development: Mild ID with IQ range of defects
40–129, mean of 78 • Cardiac (atrial septal defect, patent ductus
• Behavior: Excessive size/poor coordination arteriosus) defects, and skeletal/connective
complicates social adjustment, autism, tissue (large hands/feet, joint laxity, flat feet)
aggressiveness defects
• Tumors: Slight increased risk for malignancy

(2.2%), including Wilms tumor, several
others
IRTH DEFECT COMBINATIONS

B
AND ASSOCIATIONS
Goldenhar Syndrome/Hemifacial
Microsomia
Background
• Prevalence: 1 in 5000 live births
Fig. 4.24 A child with Goldenhar syndrome has incomplete
• Variable defect pattern from hemifacial development of the ear
microsomia to multiple facial, cardiac, and
vertebral defects Health supervision and preventive care
• Goldenhar syndrome and VACTERL associa- • Microarray analysis should be performed to
tion occur in infants of diabetic mothers exclude chromosome imbalance and whole
• Presence of minor anomalies mandates exome sequencing considered to exclude
genetic testing for chromosomal or Mendelian other Mendelian syndromes with branchial
syndromes arch defects
• Those with severe craniofacial deformity
Abnormalities should have head MRI to exclude brain
• Development: ID (5–15%) that correlates anomalies
with craniofacial severity • Craniofacial surgery team evaluation, includ-
• Growth: Low birth weight, failure to thrive ing neurosurgery, ophthalmology, ENT, and
due to dysphagia, decreased salivation, pala- feeding expertise
tal defects
• Neural: Seizures, facial palsies, encephalo-
celes, lipomas, Arnold-Chiari malformation Poland Sequence
• Face: Hemifacial microsomia, external and
middle ear anomalies (Fig. 4.24), preauricu- Background
lar tags • Prevalence: 1 in 20,000, three times more
• Eye: Epibulbar dermoids (outer quadrant), common in males, 75% right-sided
lipoepidermoid cysts (inferior quadrant), • Poland sequence is hypothesized to derive
microphthalmia from abnormal subclavian and/or vertebral
• Cardiopulmonary (VSD, tetralogy of Fallot, artery blood flow in the 6-week embryo [13],
lung hypoplasia) and renal (agenesis, hydro- linking it to Moebius and Klippel-Feil
nephrosis) defects sequence with vertebral anomalies
• Skeletal: Cervical vertebral fusion/Klippel- • Usually sporadic, but parent-child and cousin
Feil defects, vertebral anomalies, radial defect concurrence has been reported
Abnormalities (all unilateral) Health supervision and preventive care

• Chest: Absent to hypoplastic pectoralis major • Prone positioning to bring jaw forward is
muscle, absent nipple and areola, rib defects, mandatory
dextrocardia without other heart defects
• Limbs: Ipsilateral upper limb hypoplasia with
syndactyly, oligodactyly, and sometimes AMNIOTIC BAND DISRUPTION
more severe reduction defects (10% of SEQUENCE
patients with hand syndactyly are thought to
have Poland sequence) Background
• Other: Rare Sprengel anomaly, hemiverte- • Prevalence: 1 in 2000 births, much higher in
brae, renal defects abortuses
• Amniotic or Streeter’s bands, like prenatal
vascular breakdown, interfere with develop-
Pierre Robin Sequence ment of intrinsically normal tissue and thus
are termed disruptions rather than
• Prevalence: Range from 1 in 2000 to 1 in malformations
30,000 births because of variable definition • Sporadic occurrence with cocaine as a com-
• Named after surgeon Pierre Robin and not mon cause
hyphenated
• Fetal jaw growth deficiency or constraint Abnormalities
before 17 weeks is posited to be the primary • Band-produced clefts most commonly occur
anomaly, leading to defective fusion of the on the face and limbs but may disrupt any
posterior (soft) palate and protrusion of the surface region
tongue • Constricting limb bands can cause amputa-
• True isolated Robin sequence is an embryo- tions (Fig. 4.25)
logic error with sporadic occurrence • Orofacial clefts caused by bands follow a
• Many chromosomal and Mendelian syn- geographic rather than embryonic distribu-
dromes (e.g., trisomy 18, velocardiofacial, tion and can be surmised even without per-
Shprintzen syndromes) have Robin sequence sisting band remnants
as part of their anomaly pattern and must be
excluded
Abnormalities
• Lifespan: Mortality rates can be as high as
30%, often in early infancy due to obstruc-
tion/apnea
• Face: Mandibular hypoplasia (microretrogna-
thia) with displacement of the tongue
(glossoptosis)
• Palate: Interrupted closure of the lateral pala-
tine ridges with posterior U-shaped cleft of
the soft palate (the cleft in cleft lip/palate is
V-shaped and more anterior due to defects in
the primary palate)
• Respiratory: Obstruction and distress with Fig. 4.25 Six-month-old female with amniotic bands result-
ing in congenital amputation (oligodactyly)
poor feeding
• Management depends on location and ranges Minor anomalies

from extensive craniofacial surgery with • Single umbilical artery (35%) is frequent, but
parental support to hand and orthopedic sur- others may suggest syndromes like trisomy 18
gery referrals
• Thorough neonatal physical examination and
VACTERL Association (VATER appropriate imaging studies to document
Association) anomalies
• Finding of one cognate anomaly should
Background prompt evaluation for the others
• Prevalence: 1.6 per 1000 births • Generous use of genetic evaluation and test-
• Defined as an acronym for Vertebral, ing, since multiple defects often indicate
Anorectal, Cardiac, Tracheo-Esophageal, syndromes
Radial, Renal, and Limb defects, three defects
required for secure diagnosis (“trill the R” for
radial and renal) PEARLS AND PITFALLS
• The anomalies arise from embryonic meso-
dermal at 3–4 weeks post-conception Pearls
• Sporadic with low recurrence risk, provided
minor anomalies are not present to suggest a • Rare or extreme diseases are more likely to
syndrome have a significant genetic predisposition.
• Higher prevalence in infants of diabetic • For conditions with several modes of inheri-
mothers tance (e.g., deafness, epilepsy, myopathy),
autosomal recessive inheritance will produce
Major abnormalities more severe symptoms than X-linked or auto-
• Development: Normal brain function, but somal dominant inheritance.
delays and disability may ensue from a turbu- • Children with significant dysmorphology and
lent infancy with multiple surgeries and feed- ID are more likely to have chromosome
ing issues changes, while those with normal appearance
• Growth: Prenatal deficiency can occur with and acute deterioration are more likely to
frequent failure to thrive, particularly with have metabolic disorders.
tracheo-esophageal and anal defects • A good physical examination, including
• Head/neck: Large fontanels, plagiocephaly, ascertainment of minor anomalies like the
torticollis, Klippel-Feil sequence single palmar crease is paramount for distin-
• Neural: Spina bifida, hydrocephalus, tethered guishing morphologic from metabolic
cord disorders.
• Cardiac (VSD, others) and pulmonary (tra- • It is more important to recognize the likeli-
cheoesophageal fistula, laryngeal stenosis, hood of a syndrome with its risks for ID and
horseshoe lung) defects birth defects than to recognize a specific syn-
• GI (esophageal atresia), skeletal (radial aplasia/ drome diagnosis; chromosome and gene test-
club hand), renal (horseshoe kidney) defects ing appropriate to a morphologic disorder
• Genital defects: Cryptorchidism, hypospa- will provide the diagnosis.
dias, micropenis, vaginal atresia
Pitfalls 6. Bull MJ, Committee on Genetics. Health

supervision for children with Down syndrome.
• One cannot provide accurate recurrence risks Pediatrics. 2011;128(2):393–406. Erratum in:
without a diagnosis. Pediatrics. 2011;128(6):1212.
• Diagnosis of an isolated birth defect with its 7. Frías JL, Davenport ML, Committee on
low recurrence risk will be misleading if the Genetics and Section on Endocrinology.
minor anomalies and facial changes of a chro- Health supervision for children with Turner
mosomal or Mendelian syndrome are not syndrome. Pediatrics. 2003;111(3):692–702.
appreciated. 8. Committee on Genetics. American Academy
• Assuming low risks for chromosome disor- of Pediatrics: health supervision for chil-
ders like Down or Patau can be inaccurate if dren with Williams syndrome. Pediatrics.
cytogenetics to exclude translocations has not 2001;107:1192–204.
been performed. 9. Scott RH, Walker L, Olsen ØE, Levitt G,
• Overly negative and inaccurate counseling Kenney I, Maher E, et al. Surveillance for
for parents adjusting to new genetic diagno- Wilms tumour in at-risk children: pragmatic
ses can disrupt infant- parent bonding and recommendations for best practice. Arch Dis
parent-physician relationships. Child. 2006;91(12):995–9.
10. Hersh JH, Saul RA, Committee on Genetics.
Health supervision for children with fragile X
References syndrome. Pediatrics. 2011;127(5):994–1006.
11. Tinkle BT, Saal HM. Committee on genetics.
1. Wyandt HE, Wilson GN, Tonk Health supervision for children with Marfan
VS. Chromosome structure and variation: het- syndrome. Pediatrics. 2013;132(4):e1059–72.
eromorphism, polymorphism, and pathogen- 12. The Ehlers-Danlos Society. Assessing joint

esis. Singapore: Springer; 2017. hypermobility: the Beighton scoring system.
2. Tonk VS, Wilson GN. Inaccuracy of non- https://www.ehlers-danlos.com/assessing-
invasive prenatal screening demands cautious joint-hypermobility/. Accessed 17 Dec 2018.
counsel and follow-up. Am J Med Genet A. 13. Bavinck JN, Weaver DD. Subclavian artery
2016;170A(4):1086–7. supply disruption sequence: hypothesis of
3. Jones KL, Jones MC, Del Campo M. Smith’s a vascular etiology for Poland, Klippel-
recognizable patterns of human malformation. Feil, and Möbius anomalies. J Med Genet.
7th ed. Philadelphia: Elsevier-Saunders; 2013. 1986;23(4):903–18.
4. Wilson GN, Cooley WC. Preventive health
care for children with genetic conditions: pro-
viding a primary care medical home. 2nd ed.
Cambridge, UK: Cambridge University Press; Suggested Reading
2006.
American Board of Pediatrics. Content Outlines,
5. McKusick-Nathans Institute of Genetic
https://www.abp.org/content/content-out-
Medicine, Johns Hopkins University School
lines-0. Accessed 17 Dec 2018.
of Medicine. Online Mendelian Inheritance
American Academy of Pediatrics. Genetics in
in Man. https://www.omim.org/. Accessed 17
Primary Care Institute. A toolkit to improve care
Dec 2018.
for pediatric patients with genetic conditions in
primary care. https://www.aap.org/en-us/advo- testing and screening of children. Pediatrics.

cacy-and-policy/aap-health-initiatives/genetics- 2013;131(3):620–2.
in-primary-care/Documents/GPCI_Toolkit.pdf. American Academy of Pediatrics. Genetics in
Accessed 17 Dec 2018. Primary Care Institute. Genetics in primary
Committee on Bioethics; Committee on Genetics, care. https://www.aap.org/en-us/advocacy-and-
and; American College of Medical Genetics policy/aap-health-initiatives/genetics-in-pri-
and; Genomics Social; Ethical; Legal Issues mary-care/Pages/default.aspx. Accessed 17 Dec
committee. Ethical and policy issues in genetic 2018.
Metabolic Disorders
5
Osama I. Naga
Table 5.1 Major classifications of inherited metabolic

MAJOR CLASSIFICATIONS disorders
OF INHERITED METABOLIC Major classifications Inherited metabolic disorders
DISORDERS (TABLE 5.1) Protein
Organic acidemias Isovaleric acidemia, propionic
acidemia, 3-methylcrotonyl-
linical Approach to a Newborn
C CoA carboxylase deficiency,
with Suspected Inborn Errors multiple carboxylase deficiency
(biotinidase deficiency),
of Metabolism (Fig. 5.1) methylmalonic acidemia, maple
syrup urine disease (MSUD),
Clues to Metabolic Disorders glutaric acidemia type 1
Disorders of amino acid Phenylketonuria, tyrosinemia,
• Most infants are healthy at birth then become metabolism alkaptonuria homocystinuria,
progressively sick nonketotic hyperglycinemia
Urea cycle defects Ornithine transcarbamylase
• May present hours to years after birth, deficiency (OTC), carbamoyl
depending on the underlying type of meta- phosphate synthetase I
bolic disorders and possible triggers, e.g., deficiency
fasting or illness Fat
Fatty acid oxidation Medium-chain acyl-coenzyme A
Initial laboratory evaluation defects dehydrogenase deficiency
(MCAD)
• Complete blood count (CBC) Carbohydrate
–– To screen for sepsis, neutropenia, anemia, Disorders of Galactosemia, glycogen storage
and thrombocytopenia carbohydrate diseases, McArdle disease,
• Serum electrolytes, bicarbonate, and blood metabolism Pompe disease, fructose
metabolic diseases
gases levels
Others
–– To detect electrolyte imbalances and to Lysosomal storage Hurler/Hunter/San Filippo/
evaluate the anion gap (usually elevated) disorders–MPS Morquio syndromes
and acid/base status Lysosomal storage Gaucher disease, Niemann-Pick
• Blood urea nitrogen (BUN) and creatinine disorders–Lipids disease, Tay-Sachs disease,
Fabry disease
levels
Disorders of Zellweger syndrome, X-linked
–– To evaluate renal function peroxisomal function adrenoleukodystrophy (X-ALD)
Disorders of porphyrin Acute intermittent porphyria
metabolism
O. I. Naga (*) Disorders of purine or Lesch-Nyhan syndrome
Department of Pediatrics, Paul L. Foster School of Medicine, pyrimidine metabolism

144 O. I. Naga
Fig. 5.1 Clinical Newborn with poor feeding, vomiting, lethargy, seizure or coma
approach to a newborn Not responding to IV glucose or Ca
with suspected inborn
errors of metabolism. IV
intravenous, CBC Order CBC, CRP, CMP, blood culture, ammonia level, Sepsis ruled out→
and ABG most likely metabolic
complete blood count,
CRP C-reactive protein,
CMP complete metabolic Very high ammonia level
panel, ABG arterial blood Normal anion gap Normal or high ammonia level Normal ammonia
Respiratory alkalosis High anion gap Normal anion gap
gas
Urea cycle disorder Organic Acidemia Aminoacidopathy or

“Not acidotic” “Acidotic” galactosemia
• Bilirubin level, transaminases levels, pro- • If necessary, treat hyperglycemia with insulin
thrombin time, and activated partial thrombo- • Dextrose is a lifesaver in most cases of meta-
plastin time bolic disorders
–– To evaluate hepatic function
• Ammonia level Hyperammonemia
–– If an altered level of consciousness, persis- • Hyperammonemia therapy is indicated when
tent or recurrent vomiting, primary meta- urea cycle defects cause encephalopathy
bolic acidosis with increased anion gap, or • Ammonul (benzoate/phenylacetate) must be
primary respiratory alkalosis in the absence given by central line. Arginine HCl can be
of toxic ingestion mixed with Ammonul
• Blood glucose and urine pH, ketones, and • Hemodialysis
reducing substances levels • If ammonia is ≥ 500–600 mg/dL before
–– To evaluate for hypoglycemia administering Ammonul, or is ≥ 300 mg/dL
• Lactate dehydrogenase, aldolase, creatinine after giving Ammonul, consider
kinase, and urine myoglobin levels hemodialysis
–– If any evidence of neuromyopathy
Pyridoxine (B6)
Secondary tests • Give B6 for possible pyridoxine-responsive
• Plasma quantitative amino acids and inborn-errors-of-metabolism (IEM) seizures
acylcarnitines unresponsive to conventional anticonvulsants
• Urine organic acids, acylglycine, and/or
orotic acid General Rules
• Serum lactate and pyruvate levels
• Cerebrospinal fluid (CSF) lactate, pyruvate, • Metabolic acidosis
organic acids, neurotransmitters, and/or dis- –– Metabolic acidosis usually with elevated
ease-specific metabolites anion gap occurs with many IEMs and is a
• Other tests depending on individual case hallmark of organic acidemias; manifesta-
tions include tachypnea, vomiting, and
General management lethargy
• ABCs: airway, breathing, circulation • Hypoglycemia
• Intravenous (IV) access –– Hypoglycemia (plasma glucose level
• Nothing by mouth (NPO), especially no pro- < 50 mg/dL) is rare in children and may be
tein, galactose, or fructose associated with undiagnosed fatty acid oxi-
• IV dextrose (D10–D15 with electrolytes to dation defect or endocrine disorder
maintain serum glucose level at 120– • Ammonia level
170 mg/dL)
5 Metabolic Disorders 145
–– Ammonia level greater than 100 mcg/dL in Keywords to all cases of organic acidemia
the neonate and greater than 80 mcg/dL • Normal or high ammonia level
beyond the neonatal period is considered • High anion gap
elevated • Metabolic acidosis
–– Ammonia is highest in the urea cycle defects • Neutropenia
often exceeding 1000 mcg/dL and causing
primary respiratory alkalosis sometimes
with compensatory metabolic acidosis I sovaleric Acidemia (Sweaty Feet
–– Ammonia in organic acidemias, if elevated, Odor)
rarely exceeds 500 mcg/dL, and in fatty
acid oxidation defects is usually less than Background
250 mcg/dL • Also called isovaleric aciduria (IVA)
• Most are autosomal recessive enzyme defi- • Caused by isovaleric acid CoA dehydroge-
ciencies; carriers with one rather than two nase deficiency
abnormal alleles have sufficient enzyme • A rare autosomal recessive that disrupts or
(50%) for metabolism (enzyme reserve); prevents normal metabolism of the branched-
exceptions include: chain amino acid leucine
–– Ornithine transcarbamylase deficiency • Characteristic type of organic acidemia
(OTC), Hunter, Fabry, Lesch-Nyhan, and
X-linked adrenoleukodystrophy (X-ALD) Clinical presentation
exhibit X-linked recessive inheritance • Newborn period
–– Mitochondrial diseases exhibit maternal –– Episodes of severe metabolic acidosis with
inheritance if caused by mitochondrial ketosis
rather than nuclear DNA mutations –– Vomiting
–– Some porphyrias exhibit autosomal domi- –– Encephalopathy progressing to coma and
nant inheritance death if untreated
• Testing of organic acids is most sensitive in –– Sweaty feet odor
urine, and testing of amino acids is most sen- • During childhood
sitive in blood –– Usually precipitated by an infection or
• DNA testing to demonstrate mutations in the increased protein intake
genes encoding an enzyme is now easier than –– Pancytopenia and acidosis in infants who
documenting deficient enzyme activity, survive the acute attack
allowing diagnosis using cheek swab/blood
Diagnosis
samples and subsequent preimplantation
• Sweaty feet odor is a keyword
genetic/prenatal diagnosis
• Urine organic acids show elevated C5
acylcarnitine
• DNA testing
ORGANIC ACIDEMIA
Treatment
• Isovaleric acidemia
• IV glucose and bicarbonate in an acute attack
• Maple syrup urine disease (MSUD)
• Restriction in leucine intake
• Methylmalonic acidemia
• Carnitor to preserve free carnitine for mito-
• Propionic acidemia
chondrial transport and glycine to increase
• 3-Methylcrotonyl-CoA carboxylase deficiency
conversion of isovaleryl-
CoA to
• Biotinidase deficiency
isovaleryl-glycine
• Glutaric acidemia type 1
146 O. I. Naga
Maple Syrup Urine Disease (MSUD) Methylmalonic Acidemia

Background Background
• MSUD is an aminoacidopathy secondary to • Autosomal recessive
an enzyme defect in the catabolic pathway of • Deficiency of methylmalonyl-CoA mutase or
the branched-chain amino acids leucine, iso- its vitamin B12 cofactor
leucine, and valine
• Accumulation of these three amino acids and Clinical presentation
their corresponding keto acids leads to • Vomiting
encephalopathy and progressive neurodegen- • Ketoacidosis
eration in untreated infants • Hyperammonemia
• Early diagnosis and dietary intervention pre- • Thrombocytopenia
vent complications and may allow for normal • Failure to thrive in chronic cases
intellectual development • Renal failure may occur
Clinical presentation Diagnosis

• Urine smells like maple syrup with a sweet, • Elevation of methylmalonic acid in urine and,
caramel-like odor in the case of B12 deficiency, homocysteine
• Feeding difficulty in blood
• Irregular respiration • DNA testing
• Loss of Moro reflex
• Severe seizures Treatment
• Opisthotonos rigidity • Restriction of dietary protein
• Death from cerebral edema • Carnitine is useful to prevent depletion and to
maintain mitochondrial transport
Diagnosis • Liver and kidney transplantation may be
• Metabolic acidosis due to ketoacidosis curative
• Increased anion gap • Give betaine and intramuscular (IM) vitamin
• Increased leucine, isoleucine, and valine in B12 if the patient has methylmalonic aciduria
plasma (urine levels less reliable) and homocystinuria
• Detection of L-alloisoleucine is diagnostic
for MSUD (most sensitive marker)
• DNA testing Propionic Acidemia
Treatment Background
• Dietary control of leucine, isoleucine, and valine • Autosomal recessive
• Frequent monitoring of branched-chain • Deficiency in propionyl-CoA carboxylase
amino acids (even every 1–2 days in early
life) is essential because of the changing pro-
• Severe ketoacidosis with or without hyper-
tein requirements of the newborn
ammonemia in neonates
Prognosis • Infants may present with encephalopathy,
• Normal growth and development can prog- vomiting, and bone marrow suppression
ress if diagnosis and treatment occur before • Some infants may present with ketoacidosis
10 days of age due to infection or vomiting
• Cardiomyopathy is a late onset complication
Diagnosis Clinical presentation

• Urine organic acids • Alopecia
• Large amount of 3-hydroxypropionic and • Skin rash (periorificial dermatitis)
methylcitric acids in urine is the most • Failure to thrive
specific • Hypotonia
• Abnormal ketone bodies • Encephalopathy
• DNA testing • Without treatment, the patient may develop
intractable seizures, hearing loss, and
Treatment blindness
• Dietary restriction of protein < 1 g/kg/day • Sudden infant death syndrome (SIDS)
• Carnitine is helpful in preventing deficiency
and in increasing excretion of Diagnosis
propionyl-CoA • Urine organic acid
• Increased 3-methylcrotonylglycine and
Prognosis 3-hydroxyisovaleric acid with lactic acid in
• Most children die young urine
• DNA testing
Isolated Beta-Methylcrotonyl-CoA Treatment

Carboxylase Deficiency • Oral biotin
Background
• Autosomal recessive Glutaric Aciduria Type I or Glutaric
• Due to enzyme inadequate to break down Acidemia
leucine
• Age: 1–3 years Background
• Deficiency of glutaryl-CoA dehydrogenase
Clinical presentation • A defect in catabolism of lysine, hydroxyly-
• Vomiting sine, and tryptophan
• Diarrhea
• Metabolic acidosis Clinical presentation
• Hypotonia • May present with macrocephaly at birth but
• Hypoglycemia generally normal development until they have
a stressor, e.g., febrile illness, then they may
Treatment develop hypotonia, spasms, jerking, rigidity
• Long-term leucine restriction or dystonia
• Retinal hemorrhage and subdural hematoma
are usually mistaken for child abuse
Biotinidase Deficiency
Treatment
Background • Carnitine
• Deficiency in holocarboxylase synthetase or
biotinidase Summary (Table 5.2)
• Many states in the USA do newborn testing
for biotinidase
148 O. I. Naga
Table 5.2 Organic acidemia disorders Clinical presentation

Keywords (metabolic acidosis, high • Fair skin and hair
anion gap, normal or high ammonia • Hair loss
Disorders level) • Eczema (including atopic dermatitis)
Isovaleric Sweaty feet odor
• Light sensitivity
acidemia
Maple syrup Urine smells like maple or with an • Increased incidence of pyogenic infections
urine disease odor, loss of Moro reflex, severe
(MSUD) seizures, opisthotonos rigidity, positive Other manifestations of untreated PKU
plasma l-alloisoleucine • Intellectual disability (ID) (the most common
Methylmalonic Thrombocytopenia, massive urinary finding overall)
acidemia methylmalonic acid in urine
• Musty or mousy odor
Propionic Encephalopathy, bone marrow
acidemia suppression, a large amount of • Epilepsy (50%)
3-hydroxypropionic and methylcitric • Extrapyramidal manifestations (e.g.,
acid in urine parkinsonism)
Biotinidase Intractable seizures, hypotonia, ataxia, • Eye abnormalities (e.g., hypopigmentation)
deficiency developmental delays, vision problems,
hearing loss, alopecia, skin rash
Glutaric aciduria Macrocephaly, retinal hemorrhage and
Diagnosis
type 1 subdural hematoma (can be mistaken • Elevated phenylalanine levels
for child abuse) • DNA testing to demonstrate mutations in
phenylalanine hydroxylase (PAH) genes or,
rarely, in the genes promoting synthesis of its
ISORDERS OF AMINO ACID
D tetrahydrobiopterin (BH4) cofactor
METABOLISM
Imaging studies
• Phenylketonuria • Brain magnetic resonance imaging (MRI)
• Tyrosinemia studies may be indicated in older individuals
• Homocystinuria with deficits in motor or cognitive function
• Alkaptonuria • Brain MRI may show areas of demyelination
• Nonketotic hyperglycinemia and volume loss in severe cases
Dietary treatment
Phenylketonuria (PKU) • Newborn screening can detect PKU in nearly
100% of cases; thus, cognitive deficits can be
Background prevented by treatment with a low-protein
• The most common inborn error of amino acid diet and a phenylalanine- free medical for-
metabolism mula as soon as possible after birth
• The deficiency of phenylalanine hydroxylase • Genetic testing to confirm the diagnosis
(PAH) enzyme impairs the body’s ability to • Essential amino acid, vitamin, and mineral
metabolize the essential amino acid supplementations
phenylalanine
• Elevated phenylalanine levels negatively Pharmacologic management
impact cognitive function • Sapropterin, a form of the BH4 cofactor, may
lower phenylalanine levels in some patients
Non-classic phenylketonuria • Acute stroke symptoms may occur in these

patients
• Deficiency of tetrahydrobiopterin, a cofactor
for the enzyme phenylalanine hydroxylase
• Usually presents with marked hypotonia, A lkaptonuria
spasticity, posturing, and psychomotor devel-
opmental delay Background
• Autosomal recessive
• Due to deficiency of homogentisic acid
Homocystinuria dioxygenase
Background Clinical presentation

• Classic homocystinuria follows an autosomal • Black urine when left standing
recessive inheritance and has a prevalence of • Dark brown or black pigments in the diaper
1:200,000 live births • Slate blue or gray discoloration may be found
• Caused by deficiency of cystathionine in the sclerae or ear cartilage
beta-synthase • Calcifications may be palpable in the discol-
ored areas, e.g., ear cartilage
Clinical presentation (Table 5.3) • Arthritis
• Marfanoid habitus • Mitral or aortic valvulitis
• Pectus excavatum, pectus carinatum, and
genu valgum Diagnosis
• Limited joint mobility • Homogentisic acid in urine can be identified
• Lens dislocated downward and medially • DNA testing
• Developmental delay
• ID Management
• Increased risk of thromboembolism • Reduction of phenylalanine and tyrosine is a
reasonable approach
Diagnosis • Vitamin C
• Homocystinuria • Older individuals may require removal of
• Serum methylmalonic acid is the most specific lumbar discs with fusion, also may need
• High serum methionine replacement of the affected joints
• Megaloblastic anemia
• DNA testing
Treatment Table 5.3 Difference between homocystinuria and Marfan

• 50% respond to large doses of pyridoxine, syndrome
folic acid, cobalamin, and betaine with con- Homocystinuria Marfan syndrome
current methionine restriction Autosomal recessive Autosomal dominant
Intellectual disability Normal intelligence
Prognosis Ocular lens usually Ocular lens usually
• Near-normal life expectancies with some dislocated downward dislocated upward (ectopia
(ectopia lentis) lentis)
having progressive ID Limited joint mobility Lax joint (hyperflexibility)
• Half of the patients with homocystinuria will Normal aorta Aortic dilatation
have a psychiatric disease, and one-fifth will Associated with Associated with easy
have seizures thromboembolism bruising and fragile skin
150 O. I. Naga
lycine Encephalopathy (Nonketotic

G Diagnosis
Hyperglycinemia) • High level of tyrosine in plasma and succinyl-
acetone in blood and urine
Background • DNA testing
• Autosomal recessive Treatment
• Due to a defect in the glycine cleavage sys- • Nitisinone to block tyrosine metabolism, diet
tem, an enzyme complex responsible for gly- low in tyrosine and phenylalanine
cine catabolism
Tyrosinemia Type II (Oculocutaneous
• Glycine encephalopathy Tyrosinemia)
• Unremitting seizures
Cause
• Apnea
• Due to deficiency of tyrosine aminotransferase
• Hiccups
• Hypotonia Clinical presentation
• Burst suppression pattern on electroencepha- • ID in 50%
logram (EEG) • Corneal ulcer, eye pain, and excessive
• Coma tearing
• Death in infancy • Painful red papular keratotic lesions on palms
and soles
Diagnosis
• Increase glycine in CSF Management
• DNA testing for glycine cleavage system • Diet low in tyrosine, but even this may not be
gene mutations (over 6 genes in all) curative
Treatment Summary (Table 5.4)
• Sodium benzoate may help for seizures; treat-
ment is usually unsuccessful
Table 5.4 Disorders of amino acid metabolism
Keywords (normal anion gap,
yrosinemia Type I (Hepatorenal
T Disorders normal ammonia level)
Tyrosinemia) Phenylketonuria Fair hair and skin, eczema, musty
odor, intellectual disability, eye
Background hypopigmentation
• Due to deficiency of fumarylacetoacetate Homocystinuria Marfanoid features, intellectual
disability, eye lens located
hydrolase enzyme
downward and medially,
• Infants affected early, and most have a rapid thromboembolism
course to death Alkaptonuria Dark urine, calcification of ear
cartilage, arthritis
Clinical presentation Nonketotic Seizure, apnea, hiccups, coma,
• Failure to thrive hyperglycinemia death, increased glycine in CSF
Hepatorenal Failure to thrive, hepatomegaly,
• Hepatomegaly tyrosinemia (type I) RTA
• Hepatoblastoma Oculocutaneous ID, corneal ulcers, painful skin
• Associated with renal tubular acidosis (RTA), tyrosinemia (type I) lesions in palms and soles
resembling Fanconi syndrome, as well as CSF cerebrospinal fluid, RTA renal tubular acidosis, ID intel-
radiographic fraying of rickets lectual disability
Fig. 5.2 Clinical
Newborn with poor feeding, vomiting, lethargy, seizure or coma
approach to a child with Very high ammonia level, respiratory alkalosis, no acidosis
suspected urea cycle
disorders. CPS Plasma amino acids
carbamoyl phosphate
synthetase, OTC Specific amino acid elevation No specific amino acid elevation
ornithine “due to specific urea cycle enzyme deficiency”
transcarbamylase
deficiency
≠ Citrulline Æ Citrullinemia High urine orotic acid
≠ Argininosuccinic acid Æ Argininosuccinic aciduria
≠ Arginine Æ Argininemia
≠ Glutamine and alanine Æ CPS OTC deficiency
UREA CYCLE DISORDERS (UCD) • Coma

• Death (if treatment is not forthcoming or
• OTC effective)
• Citrullinemia • Female may present with a severe migraine-
• Argininemia like headache after excessive protein intake
• Argininosuccinic aciduria
• Carbamoyl phosphate synthetase (CPS) Diagnosis
deficiency • Plasma ammonia levels may exceed 2000 mg/
dL
Keywords: Serum ammonia levels may exceed • Very low BUN level
2000 mg/dL and very low BUN level, normal anion • Normal anion gap and respiratory alkalosis
gap, and respiratory alkalosis (Fig. 5.2) • Normal liver and kidney function in most
cases, unless hypoxia or shock supervenes
• Elevated ornithine, glutamine, and alanine
Ornithine Transcarbamylase (OTC) levels and relatively low citrulline levels
Deficiency • Elevated urinary orotic acid level
• DNA testing
Background
• OTC deficiency is an X-linked genetic disor- Management
der of the urea cycle • Immediate temporary discontinuation of pro-
• Associated with very high level of ammonia tein intake
in the blood • Compensatory increases in dietary carbohy-
• Mysteriously presents in childhood in other- drates and lipids
wise healthy individuals • Hemodialysis for comatose patients with
• More severe in males than females and tends extremely high blood ammonia levels; rapid
to present earlier reduction can be achieved with hemodialysis
• IV administration of sodium benzoate, argi-
Clinical presentation nine, and sodium phenylacetate
• Heavy or rapid breathing
• Lethargy
• Vomiting FATTY ACID OXIDATION
• Hypothermia DEFECTS (FAOD)
• Somnolence
• Seizures • Medium-chain acyl-CoA dehydrogenase
• Cerebral edema deficiency
• Decorticate or decerebrate posturing • Glutaric acidemia type II
152 O. I. Naga
Medium-Chain Acyl-CoA Prevention

Dehydrogenase Deficiency (MCAD) • Avoid fasting more than 4–5 h (fasting is
contraindicated)
Keywords: Fasting, anorexia from illness, hypogly- • Carbohydrate snacks at bedtime
cemia and hyperammonemia without ketosis • Carnitine is important to prevent depletion of
free carnitine by fatty acylcarnitines and inhi-
Background bition of mitochondrial transport
• Hypoketotic hypoglycemia due to MCAD • 25% of infants die before the result of the
• Beta-oxidation of fatty acids for the produc- newborn screen
tion of energy is only required during periods
of fasting
• Clinical manifestations do not become appar- Glutaric Acidemia Type II
ent unless substantial fasting has occurred
• Most common in the first 2 years of life Cause
• Deficiency of any of three genes producing
Clinical presentation the electron transfer flavoprotein cofactor for
• Vomiting and diarrhea glutaryl-CoA dehydrogenase (glutaric acide-
• Fasting-induced lethargy and hypoglycemia mia type I results from deficiency of this
• Seizure and coma are very common enzyme)
• Associated with Reye syndrome and SIDS • Inability of the body to use the protein and fat
• Between episodes of illness, affected patients for energy
are normal
Diagnosis • Neonates may present with severe hypoglyce-
• Laboratory findings during periods of decom- mia, metabolic acidosis, and hyperammonemia
pensation include hypoketotic hypoglycemia • Sweaty feet odor
and hyperammonemia provoked by fasting • Cardiomyopathy
• Elevated C6, C8, and C10 on plasma acylcar- • Severe renal cystic dysplasia
nitine (PAC) profile (Fig. 5.3)
Treatment
Treatment • Avoid fasting
• Treatment of these disorders usually includes • Carnitine to avoid depletion
the avoidance of fasting, supplementation
with carnitine, and administration of dextrose
during acute episodes
Fig. 5.3 Newborn
Plasma acylcarnitine (PAC) profile and examples of interpretation of newborn screen results
screening: Using tandem
spectrometry detection of C2, C3, C4, C5 C6, C7, C8, C9, C10 C11, C12, C13, C14, C15 C16, C17 C18
single plasma samples or
blood spots—Three Elevated C3 and C5 Elevated C6, C8 and C10 Elevated C14, C16
plasma acylcarnitine
(PAC) profiles and
examples of
interpretation. Left panel: Medium-Chain Acyl-CoA
organic acidemias. Very long-chain acyl-CoA dehydrogenase
Organic acidemias Dehydrogenase
(VLCAD)
Center panel: MCAD. Deficiency (MCAD)
Right panel: VLCAD
DISORDERS OF CARBOHYDRATE • Important not to exclude the diagnosis of

galactosemia because the urine does not con-
METABOLISM tain reducing substances
• Galactosemia • GALT assay in erythrocytes followed by
• Galactokinase deficiency DNA analysis for GALT mutations
• Glycogen storage diseases • Prenatal diagnosis is possible using DNA
• Von Gierke disease analysis of chorionic villi or cultured amni-
• Pompe disease otic cells
• McArdle disease • Heterozygous and homozygous mothers are
• Adenylate deaminase deficiency instructed to follow a galactose-free diet
• Deficiency of fructose 1, 6-bisphosphate throughout their pregnancies
aldolase
Treatment
• Fructokinase deficiency
• Elimination of galactose from the diet
Keywords: Hypoglycemia, hepatosplenomegaly,
Complications
jaundice, weakness
• E. coli sepsis could be the initial presentation
• Ovarian failure, amenorrhea
Galactosemia • Developmental delay and learning disability
even with proper treatment
Background
• Hereditary galactosemia is among the most
common carbohydrate metabolism disorders Galactokinase Deficiency
• Can be a life-threatening illness during the
• Cataract alone
newborn period
• Chromosome 17
• Galactose-1-phosphate uridyl transferase
• Treatment is a restriction of galactose
(GALT) deficiency is most common
Glycogen Storage Diseases
• Jaundice
• Vomiting • 0—Glycogen synthase deficiency
• Lethargy • Ia—Glucose-6-phosphatase deficiency (von
• Irritability Gierke disease)
• Hypoglycemia • II—Acid maltase deficiency (Pompe disease)
• Seizure • III—Debranching enzyme deficiency
• Cataract (Forbes-Cori disease)
• Vitreous hemorrhage • IV—Transglucosidase deficiency (Andersen
• Hepatosplenomegaly disease, amylopectinosis)
• Cirrhosis • V—Myophosphorylase deficiency (McArdle
• Ascites disease)
• Poor weight gain
• VI—Phosphorylase deficiency (Hers disease)
• ID
• VII—Phosphofructokinase deficiency (Tarui
Diagnosis disease)
• Clinically
• Reducing substance in urine
154 O. I. Naga
on Gierke Disease (Glucose-6-

V • Type II glycogen storage disease
Phosphate Deficiency) • Due to acid alpha-1, 4-glucosidase deficiency

• Autosomal recessive • Infantile form
• Age: Early infancy –– Most severe form
–– Infant is usually normal at birth but
Clinical presentation soon develops generalized muscle weak-
• Hypoglycemia ness, macroglossia, hepatomegaly, and
• Lactic acidosis cardiomegaly
• Hyperuricemia –– Death < 1 year
• Hyperlipidemia • Juvenile/late childhood
• Neutropenia –– Muscle weakness
• Hepatomegaly without elevated liver enzymes –– Respiratory and digestive symptoms with-
• Doll-like face (fatty cheeks), thin extremities out cardiac involvement
• Failure to thrive –– Death may occur before the 20s
• Seizures
Diagnosis
Associated problems • Electrocardiogram (ECG) shows high volt-
• Gout age QRS and shortened PR interval
• Hepatic adenoma • Elevated CPK, AST, and LDH
• Pulmonary hypertension • The muscle biopsy will show vacuoles that
• Pancreatitis full of glycogen on staining
• DNA testing
Diagnosis
• No response to glucagon or epinephrine Treatment
• DNA testing • Unfortunately, no cure exists
• Enzyme replacement therapy (ERT) may
Management benefit the patients, especially if combined
• For older children, uncooked cornstarch will with immune modulation
sustain blood glucose for 4–6 h
• For young children, continuous nasogastric
tube feeding of glucose is necessary to sus-
tain normal blood glucose level, especially at
McArdle Disease, Muscle
night Phosphorylase Deficiency
• If surgery is required, a continuous infusion
Background
of glucose 24–48 h prior to surgery
• Chromosome 11q13
Pompe Disease
Background • Usually in the 20s to 30s
• Autosomal recessive • Exercise-induced cramps and exercise
• Located on chromosome 17 intolerance
• Burgundy-colored urine due to myoglobin- Clinical presentation

uria and rhabdomyolysis • Infant is healthy until fructose or sucrose is
ingested, e.g., juice or sweetened cereals
Diagnosis • Jaundice, vomiting, lethargy, seizures, and
• Elevated CPK at rest irritability
• DNA testing • Hepatomegaly
• Elevated liver enzyme
Treatment • Prolonged clotting factors
• Avoid strenuous exercise to prevent • If sugar intake continued, will lead to hypo-
rhabdomyolysis glycemia, organ failure, and death
• Oral fructose/glucose intake can improve
exercise tolerance Diagnosis
• Reducing substances in urine during the
episode
Adenylate Deaminase Deficiency • IV fructose will cause hypoglycemia and
hypophosphatemia
Background
• Autosomal recessive trait Treatment
• Avoid all sources of fructose, sucrose, and
sorbitol
• Muscle weakness
• Cramping after strenuous exercise Prognosis
• Very good; however, reversal of damage and
Diagnosis
ID is uncommon
• CPK level may be increased
• No myoglobinuria
• Muscle biopsy is normal Fructokinase Deficiency
• DNA testing
Background
Treatment • Deficiency of the enzyme hepatic fructoki-
• Oral D-ribose may prevent the symptoms if nase is a clinically benign condition character-
given at the beginning of the exercise ized by the incomplete metabolism of fructose
in the liver, leading to its excretion in urine
Fructose 1,6-Diphosphatase Clinical presentation
Deficiency • Asymptomatic
Keywords: Healthy infant begins to have symp- Diagnosis

toms after the introduction of juice or any source • Fructosuria
of fructose or sucrose • Reducing substance in urine
• DNA testing
Background
• Autosomal recessive Treatment
• Age 4–6 months • No treatment required
Summary (Table 5.5)
156 O. I. Naga
Table 5.5 Disorders of carbohydrate metabolism • Large tongue

Disorders Keywords • Umbilical or an inguinal hernia, large head
Galactosemia Hypoglycemia, cataracts, jaundice, > 95%
hepatosplenomegaly, seizures • Recurrent upper respiratory infections
Von Gierke disease Hypoglycemia, hyperlipidemia,
(glucose-6- hyperuricemia, lactic acidosis,
• Hepatosplenomegaly
phosphate hepatosplenomegaly, distended • Cardiac disease (valvular or coronary
deficiency) abdomen, doll-like faces with involvement)
chubby cheeks, thin extremities, • Atlantoaxial subluxation
short stature • Corneal clouding
Pompe disease Muscle weakness, cardiomegaly,
elevated CPK
• Deafness
McArdle disease Muscle cramps with exercise,
myoglobinuria, elevated CPK Prognosis
Fructose Healthy infant until juices (sucrose • Related to cardiac involvement: Can involve
1,6-diphosphatase or fructose) are introduced, early cardiomyopathy and death
deficiency hypoglycemia, seizures, vomiting, • Some mildly affected due to different iduron-
hepatomegaly, coma if fructose or
sucrose intake continued idase alleles, formerly grouped as MPS V or
Fructokinase Asymptomatic fructosuria Scheie syndrome
deficiency
MPS Type II (Hunter Syndrome)

LYSOSOMAL STORAGE • Defect in iduronate-2 sulfatase on chromo-
DISORDERS: some Xq27-28
MUCOPOLYSACCHARIDOSES • Only males are affected (only in females with
non-random lyonization)
Mucopolysaccharidosis (MPS)
Background • Present in the first 2 years of life
• Group of disorders due to a defect in the • No corneal clouding
catabolism of glycosaminoglycans and accu- • Coarse facial features
mulation of macromolecules in target organs • Learning difficulties
• All MPS autosomal recessive except Hunter • Middle ear disease
syndrome, which is X-linked • Joint stiffness
• Patients with MPS have normal development • Hepatosplenomegaly
initially • Skin rash: pebbly ivory skin lesions on the
• Abnormalities are seen in infancy or some- back, arms, and thighs (pathognomonic but
times later in childhood rare in children)
MPS Type I (Hurler Syndrome) MPS Type III (Sanfilippo Syndrome)

• Defect in L-iduronidase • Inability to catabolize heparan sulfate
Clinical presentation Clinical presentation
• Coarsened facial features • Coarse hair
• Midface hypoplasia • Clear cornea
• Developmental delay LYSOSOMAL STORAGE

• Severe challenging behavior and hyperactivity
• Aggression and unaware of self-harming
DISORDERS: LIPIDOSES
• Sleep disturbance • Gaucher disease
• Progressive dementia • Niemann-Pick disease
• Swallowing dysfunction • Krabbe disease
• May deteriorate to vegetative state • Tay-Sachs disease
• Fabry disease
• Wolman disease
MPS Type IV (Morquio Syndrome)
• Metachromatic leukodystrophy
• Defect in galactosamine-6-sulfatase Keywords: Splenomegaly, seizures, cherry-red
• Leads to defective degeneration of keratan spot
Gaucher Disease
• Short trunk dwarfism (final height < 125 cm)
• Fine corneal deposits Background
• Skeletal dysplasia • Gaucher disease is a lipid storage disease
• Normal intelligence characterized by the deposition of glucocere-
• Odontoid dysplasia broside in cells of the macrophage-monocyte
system
General treatment of MPS
• The disorder results from the deficiency of
• Bone marrow transplantation may prevent
the enzyme glucocerebrosidase
intellectual deterioration and increase sur-
vival rate
• Age 2–18 years
• Enzyme replacement therapy is the treatment
• Mutations in Ashkenazi Jews > 95%
of choice
• All forms of Gaucher usually develop hepato-
• Orthopedic surgery for spinal deformity
splenomegaly, bone lytic lesions, and some
Summary (Table 5.6) lung diseases
Types of Gaucher disease

Table 5.6 Lysosomal storage disorders—mucopolysac- • Type 1—non-neuronopathic form (most com-
charidoses (MPS) mon and does not affect the CNS)
Disorders Keywords • Type 2—acute neuronopathic form
MPS general Coarse facial features, organomegaly, • Type 3—chronic neuronopathic form
features bony deformities, developmental
regression, sensory loss (hearing and Clinical presentation
vision) • Growing pain in lower extremities, especially
Hurler MPS general manifestations, mental
syndrome deficiency, cloudy cornea
at night due to bone infiltration
(MPS type I) • Skin pigmentation
Hunter Mild MPS general manifestations, a boy • Splenomegaly
syndrome (x-linked R) with no cloudy cornea • Abdominal protuberance due to the very large
(MPS type II) spleen
Sanfilippo Behavioral problems, aggression,
syndrome self-harming, progressive dementia, clear
• Hypersplenism; significant thrombocytope-
cornea nia, can result in severe bleeding, pallor, and
Morquio Short stature, short trunk dwarfism, bone anemia
syndrome dysplasia, fine corneal opacities
158 O. I. Naga
Diagnosis • Supranuclear and vertical-gaze palsy

• Bone marrow aspiration: Gaucher storage • Voluntary, vertical eye movement is usually
cells wrinkled paperlike tissue lost, but reflex and doll-eye movement are
• Deficiency of glucocerebrosidase in leuko- preserved
cytes and cultured skin • Death in the teens is common
• Loss of bone tabulation on radiograph
• DNA testing Diagnosis
• Intra-lysosomal accumulation of unesterified
Treatment cholesterol in cultured fibroblast
• Splenectomy is contraindicated • DNA testing
• Enzyme replacement therapy (ERT) for type 1
Gaucher disease, e.g., imiglucerase (Cerezyme)
Krabbe Disease
Niemann-Pick Disease (NPD) Background

Background • Mutation in the GALC gene located on chro-
• NPD is a lipid storage disorder mosome 14 (14q31)
• Due to deficiency of acid sphingomyelinase • β-Galactocerebrosidase deficiency and white
• NPD type A matter accumulation of galactosylceramide in
–– Very rare neurovisceral disease peripheral and central myelin, resulting in
–– Occurs mainly in Ashkenazi Jews spasticity and cognitive impairment
–– Hepatosplenomegaly
–– Progressive loss of motor skills Clinical presentation
–– Cherry-red spot • Convulsions
• NPD type B • Quadriplegia
–– Common in Ashkenazi Jews • Blindness, deafness
–– Inherited as autosomal recessive traits • ID
–– Isolated splenomegaly • Progressive neurologic symptoms that lead to
• NPD type C death by age 2
–– Results from defects in cholesterol
metabolism Treatment
–– Located on chromosome 18 • No cure
–– Age: 3–4 years of age • Bone marrow transplantation may benefit
–– Due to cholesterol ester accumulation in early in the course of the disease
the lysosome
Clinical presentation of NPD type C ay-Sachs Disease

T
• Dysphagia is common and may lead to a
Background
feeding tube
• Due to deficiency of beta-hexosaminidase
• Poor school performance in older children
alpha subunit
• Cataplexy and narcolepsy are very common
• Neurons have lamellar inclusions
• Ataxia
• No visceral involvement
Clinical presentation Treatment

• Noise or light startles the infant with a quick • Painful peripheral neuropathy may respond
extension of the arms and legs with clonic to carbamazepine or gabapentin
movement (unlike Moro reflex, this does not • IV alpha-galactosidase may relieve pain
diminish with repeated stimuli) • Renal transplant for end-stage renal disease
• Axial hypotonia
• Extremities hypertonia and hyperreflexia
• Seizure to auditory stimuli Wolman Syndrome
• By 2–3 years of age, the child is usually in
decerebrate posture, has become blind, and is Keywords: Relentless vomiting in the 1st week
unable to respond to stimuli after birth, failure to thrive, and calcification of
• Cherry-red spot > 90% of cases adrenal glands
Juvenile and adult form Background

• Occurs in Ashkenazi Jews • A milder form of lipoprotein lysosomal acid
• Affected children usually labeled clumsy and lipase deficiency
awkward • Termed cholesteryl ester storage disease
• Proximal muscle weakness occurs with • May not manifest until adult life
fasciculations
• Anxiety, depression, suicide Clinical presentation
• May ambulate until the age of 60s • Feeding difficulties with frequent vomiting
shortly after birth
• Diarrhea, steatorrhea
Fabry Disease • Failure to gain weight or sometimes weight loss
• Abdominal distention
Background • Hepatosplenomegaly
• Deficient activity of lysosomal enzyme • Liver dysfunction or failure
α-galactosidase (α-Gal A) • Severe anemia
• Only sphingolipidoses transmitted as • Calcifications of adrenal glands
X-linked (pathognomonic)
• Increased risk of premature atherosclerosis
Clinical presentation • Very few infants with Wolman disease sur-
• Severe episodic pain in hands and feet vive beyond the 1st year of life
• Hypohidrosis or anhidrosis
• Angiokeratoma (dark red, blue-black, flat or Diagnosis
slightly raised punctate skin lesions) • Variable hypertriglyceridemia usually present
• Corneal opacities • Hypercholesterolemia
• Congestive heart failure • Bilateral adrenal calcifications on CT scan
• Chronic abdominal pain and diarrhea • DNA testing
• Renal failure
• Autonomic nervous system dysfunction
• Seizures, hemiparesis, and ataxia Metachromatic Leukodystrophy
Diagnosis Background
• (α-Gal A) activity may be measured in • Lysosomal storage diseases
plasma, serum, and leukocytes • Progressive, inherited, and neurodegenerative
• DNA testing disorders
160 O. I. Naga
Table 5.7 Lysosomal storage diseases—lipidoses gens, which contribute in great part to the
Disorders Keywords phospholipid content of the brain white
Gaucher disease Protruded abdomen, splenomegaly, matter
bone pain, bone lytic lesions, pathologic
fractures, thrombocytopenia, anemia Examples of peroxisomal disorders
Niemann-Pick Hepatosplenomegaly, psychomotor
• Zellweger syndrome
disease retardation, cherry-red spot, death by
3 years of age • X-ALD
Krabbe disease Convulsions, mental deterioration,
spasticity, blindness, most die by Keywords: Hypotonia, seizures, elevated
3 years of age VLCFA
Tay-Sachs Seizure to auditory stimuli, ataxia,
disease hypertonia, cherry-red spot, mental
deterioration Zellweger Syndrome
Fabry disease Burning pain in hands and feet,
angiokeratoma, hypohidrosis, corneal Clinical presentation
opacities
Wolman disease Relentless vomiting after birth, failure • Typical craniofacial dysmorphism; high fore-
to thrive, calcification of adrenal glands head, a large anterior fontanelle, hypoplastic
Metachromatic Inability to walk, motor delay, supraorbital ridges, broad nasal bridge,
leukodystrophy diminished reflexes, hypotonia, optic micrognathia, deformed earlobes, and redun-
atrophy, seizures
dant nuchal skinfolds
• Neurologic features; severe psychomotor
Clinical presentation retardation, profound hypotonia with
• Gait disturbances depressed deep tendon reflexes (DTRs), neo-
• Loss of motor developmental milestones natal seizures, and impaired hearing
• Loss of previously achieved skills • Brain, cortical dysplasia
• Truncal ataxia • Ocular features; congenital cataract, glau-
• Memory deficits coma, and retinal degeneration
• Seizures (may be present) • Calcific stippling of the epiphysis or patella
• Tremors • Small renal cysts
• Optic atrophy • Liver cirrhosis
Diagnosis Diagnosis
• Arylsulfatase A enzyme activity may be • Suspect diagnosis by increased VLCFA or
decreased in leukocytes decreased plasmalogens
• DNA testing • DNA testing to demonstrate mutations in
genes mediating peroxisomal biogenesis and/
Treatment
or transport
• No effective treatment to reverse neurological
deterioration Prognosis
• Summary (Table 5.7) • Most die by 1 year of age
PEROXISOMAL DISORDERS X-Linked Adrenoleukodystrophy

(X-ALD)
• Peroxisomes are essential for beta-oxidation
of very long-chain fatty acids (VLCFA) and Background
detoxification of hydrogen peroxide • Affects males
• Peroxisomes are also involved in the produc- • Accumulation of VLCFA in the white matter,
tion of cholesterol, bile acids, and plasmalo- peripheral nerves, adrenal cortex, and testis
• DNA testing allows diagnosis of carrier DISORDERS OF PORPHYRIN

females and preimplantation genetic/prenatal
diagnosis
METABOLISM (PORPHYRIAS)
• Enzyme defect in heme synthesis
• Overproduction and accumulation of porphyrin
• Early development is entirely normal
• Development may regress after 3–5 years of Keywords: Skin hypersensitive to sunlight, skin
age hyperpigmentation, liver dysfunction
• Early manifestations are often mistaken for
attention deficit hyperactivity disorder
(ADHD) Acute Intermittent Porphyria (AIP)
• Progressive neurological disorders include
impaired auditory discrimination, visual dis- Background
turbances, spatial disorientation, and poor • AIP is an autosomal dominant disease that
coordination; seizures ensue later in the results from defects in the enzyme
disease porphobilinogen-deaminase
• Adrenal insufficiency • This enzyme speeds the conversion of por-
• Progression leads to a vegetative state in phobilinogen to hydroxymethylbilane
2 years and then death
The most common drugs induce AIP
Diagnosis • Barbiturate, sulfa, carbamazepine, valproic
• Elevated level of VLCFA acid, griseofulvin, birth control pills
• Brain MRI pattern is quite characteristic:
–– Lesions are symmetrical, and demyelin- Clinical presentation
ation is progressive • Abdominal pain is the most common
–– Late in the disease, the brain stem and ulti- symptom
mately the cerebellum may be involved • Ileus, abdominal distension, and decreased
• DNA testing allows diagnosis of carrier bowel sounds
females and preimplantation genetic/prenatal –– Nausea and vomiting
diagnosis –– No abdominal tenderness and no fever
Summary (Table 5.8) because it is neurological and not
inflammatory
Table 5.8 Peroxisomal disorders • Dysuria and urinary retention may occur
Disorders Keywords • Limb, neck, and chest pain
Zellweger syndrome Abnormal facial features, severe • Mental changes: anxiety, depression, insom-
weakness, hypotonia, failure to nia, and paranoia during the acute attacks
thrive, eye abnormalities, elevated
• Peripheral neuropathy: Proximal muscle
VLCFA
X-linked ADHD-like symptoms, vision weakness, some sensory changes
adrenoleukodystrophy problems, poor coordination, • Most patients are symptom-free between
(X-ALD) adrenal insufficiency, elevated attacks
VLCFA, brain MRI shows
demyelination
VLCFA very long-chain fatty acids
162 O. I. Naga
Diagnosis rythropoietic Protoporphyria

E
• Elevated level of porphobilinogen (> 6 mg/L)
on a spot urine test during an acute attack will Background
confirm diagnosis • Autosomal dominant
• DNA diagnosis • Due to partial deficiency of ferrochelatase
Treatment Clinical presentation

• High doses of glucose can inhibit heme syn- • Hypersensitivity to sunlight exposure (pain-
thesis and are useful for the treatment of mild ful skin)
attacks • Skin hyperpigmentation
• Hematin in severe attacks with severe neuro- • Skin edema, erythema, and petechiae after
logical symptoms more prolonged exposure to sunlight
• Narcotics, laxatives, and stool softeners • Blisters, crusted erosions, and scarring may
occur
• Gallstones with or without abdominal pain
Porphyria Cutanea Tarda • Hepatotoxicity and jaundice may exacerbate
photosensitivity
Background
• Occur after exposure to halogenated aromatic Diagnosis
hydrocarbons, e.g., excess alcohol • Elevated levels of protoporphyrin in bone
• Excess iron and estrogen are also a common marrow, RBCs, plasma, bile, and feces is
cause diagnostic
• The most common of porphyrias • DNA diagnosis
• Due to the deficiency in hepatic
URO-decarboxylase Treatment
• Avoidance of sunlight (protective clothing
Clinical presentation and lifestyle changes)
• Cutaneous photosensitivity • Vitamin D3
• Fluid-filled vesicles and bullae on sun- • Activated charcoal may increase excretion of
exposed areas protoporphyrin
• Hypertrichosis • Transfusion and IV heme may be helpful in
• Hyperpigmentation reducing protoporphyrin production
Diagnosis Summary (Table 5.9)

• Presence of high level of porphyrin in the
liver, plasma, urine, and stool helps with Table 5.9 Disorders of porphyrin metabolism (porphyrias)
diagnosis Disorders Keywords
• Low level of hepatic URO-decarboxylase in Acute Abdominal pain, psychiatric symptoms,
red blood cells (RBCs) intermittent peripheral neuropathies, completely free
• DNA diagnosis porphyria symptoms between attacks
Porphyria Skin photosensitivity,
cutanea tarda hyperpigmentation, hypertrichosis
Treatment Erythropoietic Painful skin after sun exposure, skin
• Avoid exposure to offending agents, e.g., sun- protoporphyria edema with or without redness,
light, estrogen, alcohol, or tobacco smoking gallstones, abdominal pain, jaundice,
• Therapeutic phlebotomy reduces iron stores photosensitivity
ISORDERS OF PURINE OR
D VARIOUS METABOLIC
PYRIMIDINE METABOLISM DISORDERS
Lesch-Nyhan Disease Familial Hypercholesterolemia
(Hypoxanthine-Guanine
Background
Phosphoribosyltransferase
• Very common 1/200–1/500
Deficiency) • Autosomal dominant
Keywords: Kidney stones, high uric acids, and Clinical presentation
self-mutilation • Xanthomas: planar xanthomas with yellow-
to-orange discolorations on hands, elbows,
Background buttocks, or knees. Tendon xanthomas (espe-
• Lesch-Nyhan disease is X-linked cially on extensor tendons of hands or Achilles
• Affects mainly boys tendon)
• Due to deficiency of hypoxanthine-gua- • An untreated male will develop coronary
nine phosphoribosyltransferase (HPRT) heart disease 100%, untreated female, 75%
deficiency
Diagnosis
Clinical presentation • Cholesterol level 600–1000 mg/dl
• Usually, males are healthy at birth • DNA diagnosis showing LDL receptor
• Failure to thrive mutations
• Vomiting
• Self-mutilation Management
• Lips and finger biting • Statins are the recommended initial therapy
• Kidney stones for dyslipidemia in children and adolescents
• Gout (see also Chap. 19 Cardiology)
Diagnosis Differential diagnosis

• High level of uric acid • Sitosterolemia: Tendon xanthoma in
• HPRT deficiency on RBCs the first decade but only moderate
• DNA diagnosis hypercholesterolemia
Treatment
• Supportive mith-Lemli-Opitz Syndrome
S
• Hydration and allopurinol (inhibiting the
metabolism of hypoxanthine and xanthine to Keywords: Low cholesterol, abnormal facial fea-
uric acid) tures, and developmental delay
164 O. I. Naga

• Autosomal recessive • Premature delivery
• A defect in cholesterol biosynthesis • Abnormal feature: Facies, pudgy cheeks; sag-
• Deficient activity of 7-dehydrocholesterol ging jowls and lips
reductase • Hair and eyebrows are sparse
• Cholesterol is important for embryogenesis • Kinky hair (pili torti under the microscope)
• Survival is unlikely if cholesterol is < 20 mg/dL • Hypothermia or temperature instability
• Hypotonia
Clinical presentation • Hypoglycemia
• Microcephaly • Seizures
• Narrow bifrontal diameter • Loss of milestones
• ID • Progressive neurological deterioration
• Ptosis
• Hypertelorism Diagnosis
• Cataracts • Low-serum copper and ceruloplasmin
• Low-set ears • Copper and ceruloplasmin levels may be nor-
• Anteverted nostrils mal in the milder variants and in the neonatal
• Broad maxillary alveolar ridge period
• Cleft palate • DNA testing for mutations in the ATP7A gene
• Micrognathia
• Postaxial polydactyly
• Hypospadias BODY ODORS
• Ambiguous genitalia
Trimethylaminuria, also called fish odor
Diagnosis syndrome
• Elevated dehydrocholesterol • Decaying fish odor
• Low cholesterol or normal
• DNA diagnosis MSUD
• Caramel, maple syrup, or malty odor
Treatment
• Dietary cholesterol (egg yolk) Phenylketonuria
• Statins to prevent the synthesis of toxic pre- • Musty like odor
cursors proximal to the enzymatic block
Multiple acyl-CoA dehydrogenase deficiency
• Variable sweaty feet body odor
Menkes Disease (Kinky Hair Disease)
Isovaleric acidemia
Keywords: Presents at birth, kinky and sparse • Cheesy, acrid, sweaty feet odor
hair, hypoglycemia, seizures, progressive neuro-
Tyrosinemia
logical and developmental deterioration
• Cabbage or rancid butter odor
Background Diabetes mellitus and diabetic ketoacidosis

• X-linked disease • Fruity breath
• Impaired uptake of copper
3-methylcrotonylglycinuria –– MS/MS is sensitive, reliable, and more

• Male cat urine like odor comprehensive than Guthrie methods
–– Elevations in the first spectrogram are
Cystinuria routed to the second (tandem) spectrome-
• “Rotten egg” odor because cystine is one of ter to define metabolite structure
the sulfur-containing amino acids –– MS/MS displays all amino or organic acid
metabolites, diagnosing ~56 disorders
Hypermethioninemia (expanded newborn screen) when com-
• Fishy, sweet and fruity, rancid butter or boiled bined with testing for hemoglobinopathies,
cabbage odor congenital adrenal hyperplasia (CAH), and
cystic fibrosis (CF); trypsin
NEWBORN METABOLIC
SCREENING PEARLS AND PITFALLS
• Is intended to detect congenital genetic and
metabolic disorders that can result in early • Nothing by mouth (NPO) and IV dextrose is
mortality or lifelong disability the best initial treatment for any newborn or a
• Such screening was a pediatric innovation child with suspected metabolic disorders,
where the principle of beneficence was first regardless of the type of metabolic disorder,
applied: Screen only if diagnosis improves and is a life saver.
outcome • Organic acidemia should be suspected in a
• Uses heel stick blood spots, engineered to patient who presents with hypoglycemia and
have frequent false positives so that diagno- hyperammonemia in the presence of meta-
ses are rarely missed bolic acidosis.
• Began using phenylalanine (phe)-dependent • Some organic acidemias also result in granu-
bacteria with turbid growth showing elevated locytopenia and thrombocytopenia and are
phe levels (Guthrie test for phenylketonuria, mistaken for sepsis.
hence often called the “PKU’ test) • Urea cycle defects are associated with very
• In the USA such screening is state coordi- high ammonia level, normal anion gap (not
nated, dictating that pediatricians collect ini- acidotic), and respiratory alkalosis.
tial (1–3 days) and follow-up samples as • MSUD in a newborn who appears well in the
needed (poor feeding may cause negative first 1 or 2 days after birth and then becomes
screens) irritable, feeds less, drowsy, lethargic, apneic;
• States provide reports of abnormal screens to opisthotonus, hypertonia, ketonuria, and a
pediatricians with instructions for family maple syrup odor.
communication, follow- up, and ACTion
(ACT) sheets outlining initial therapy Acknowledgment I gratefully acknowledge the
• Now tandem mass spectrometry (MS/MS) is review and suggestions of Golder N. Wilson, MD,
used to detect any elevated metabolite in heel- PhD, Clinical Professor of Pediatrics, Texas Tech
stick blood spots: University Health Science Center, Lubbock, Texas.
166 O. I. Naga
Suggested Reading Rezvani I, Rezvani G. Approach to inborn errors

of metabolism. In: Kliegman RM, Stanton
Berry GT, Segal S, Gitzelmann R. Disorders BF, St. Geme III JW, Schor NF, Behrman RE,
of galactose metabolism. In: Fernandes J, editors. Nelson textbook of pediatrics. 19th
Saudubray M, van den Berghe G, Walter JH, edi- ed. Philadelphia: Saunders Elsevier; 2011.
tors. Inborn metabolic diseases—diagnosis and p. 416–48.
treatment. 4th ed. New York: Springer; 2006. Rezvani I, Yukoff M. Urea cycle and hyperammo-
Grabowski GA. Phenotype, diagnosis, and nemia. In: Kliegman RM, Stanton BF, St. Geme
treatment of Gaucher’s disease. Lancet. III JW, Schor NF, Behrman RE, editors. Nelson
2008;372:1263–71. textbook of pediatrics. 19th ed. Philadelphia:
Kim HJ, Park SJ, Park KI, Lee JS, Eun HS, Kim JH, Saunders Elsevier; 2011. p. 447–53.
et al. Acute treatment of hyperammonemia by Wanders RJ. Peroxisomes, lipid metabolism,
continuous renal replacement therapy in a new- and human disease. Cell Biochem Biophys.
born patient with ornithine transcarbamylase 2000;32(Spring):89–106.
deficiency. Korean J Pediatr. 2011;54:425–8.
Mental and Behavioral Health
6
Mohamed Hamdy Ataalla
Table 6.1 Classification of intellectual disability (ID)

NEURODEVELOPMENTAL Educational Independence/skills
DISORDERS ID level level achievement
Mild IQ Up to sixth Independent in personal care
Intellectual Disability (ID) (50–69) grade and activities of daily living
with minimal support;
independent employment with
• Previously called mental retardation
a possible need for minimal
• Subnormal intellectual and adaptive function- supervision or support
ing with onset in the developmental period Moderate Up to third Can care for personal needs
• Classification according to IQ level (Table 6.1) IQ grade and activities of daily living;
1. Mild IQ 50–70 (majority of cases) (36–49) limited support needed in daily
situations; supportive living,
2. Moderate 35–49 e.g., group home; supported or
3. Severe 20–34 supervised work; unskilled or
4. Profound < 20 semiskilled job
• Prevalence: 1–2%, higher in ethnic minorities Severe IQ Limited Needs support for personal
and with lower socioeconomic status (20–35) academic care and activities of daily
skills living at all times; safety
supervision; possible
Causes recognition of critical words
• Congenital infections (e.g., cytomegalovirus, (e.g., “no”); needs a nursing
rubella, toxoplasmosis) home; sheltered work with
• Central nervous system infections (e.g., men- extensive support needed in all
ingitis, encephalitis) daily activities
Profound Not Dependent on others for every
• Trauma IQ (< 20) applicable aspect of daily activities, needs
• Malignancy nursing care, not employable
• Genetic abnormalities (e.g., trisomy 21, frag-
ile X syndrome)
–– Down syndrome: Most common genetic Clinical presentation
cause of ID • May suffer significant psychiatric problems:
• Inborn errors of metabolism Same range of psychiatric disorders but
• Teratogens (e.g., alcohol, illicit and prescrip- higher rate and more difficult to diagnose
tion drugs, lead, radiation) • Those with severe or profound ID may pres-
ent with dysmorphic features and other signs
of congenital anomalies
M. H. Ataalla (*) • Prader–Willi syndrome: Hyperphagia and
Department of Child and Adolescent Psychiatry, Texas Tech compulsive behaviors

168 M. H. Ataalla
• Fragile X syndrome: Attention and social 3. Restricted range of interests and stereotyp-
problems ical body movements
• Angelman syndrome: Inappropriate laughter • Early problems with joint attention behav-
• Sanfilippo syndrome: Coarse facial features iors, e.g., lack of eye contact, no pointing to
and mild hepatosplenomegaly share attention
• Fetal alcohol syndrome: Differences in • ASD presentation can be very heterogeneous
growth (i.e., weight and/or height ≤ 10th per- with various levels of cognitive functioning
centile), smooth philtrum, thin upper lip, and language skills
small palpebral fissures; central nervous sys- • Asperger syndrome: Formerly (before DSM-
tem abnormalities (e.g., microcephaly, sei- 5) classified as a separate pervasive develop-
zures, intellectual disability, learning mental disorder diagnosis, as these patients
disabilities, attention-deficit/hyperactivity had higher verbal ability compared to the
disorder [ADHD]) other autistic patients
Differential diagnosis/associated conditions Differential diagnosis/associated conditions

• Language disorder: For children with lan- • Intellectual disability (frequently occurs with
guage difficulties, use nonverbal IQ test ASD)
• Autistic spectrum disorder (sometimes asso- • Epilepsy
ciated with ID) • Specific developmental language disorders
• Specific learning disability (academic under- • Early-onset psychosis (e.g., schizophrenia)
performance despite normal IQ level) • Selective mutism and social anxiety
• Simple stereotypic movements: Normal in
Management children less than 3 years old
• Psychosocial interventions • Stereotypic movement disorders: Complex,
• Cognitive and adaptive interventions persisting after the age of 3 years; absence of
• Treat associated psychiatric and medical impairment in communication and social
conditions interactions
• General quality of life measures • Emotional neglect, and reactive attachment
disorder (inhibited type)
Autism Spectrum Disorders Screening and testing

• Early detection: Checklist for Autism in
• All previously called pervasive developmen- Toddlers (CHAT), the Modified Checklist for
tal disorders now fall under the diagnosis of Autism in Toddlers (M-CHAT)
autism spectrum disorder (ASD), according (https://m-chat.org/), and the Pervasive
to the American Psychiatric Association’s Developmental Disorders Test II (PDDST-II)
Diagnostic and Statistical Manual of Mental screening test
Disorders (DSM-5) • School district referral for comprehensive
evaluation in children 3 years and older
Diagnostic criteria
• The gold standard diagnostic tools: The
• ASD is diagnosed clinically
Autism Diagnostic Interview-Revised (ADI-
• Three cardinal features:
R) and the Autism Diagnostic Observation
1. Impairment in social interaction Schedule (ADOS)
2.
Impaired verbal and nonverbal
communication
6 Mental and Behavioral Health 169
• Neuropsychological and achievement assess- COMMUNICATION DISORDERS

ment, e.g., IQ testing
• Medical workup to rule out associated genetic S peech Disorders
condition if clinically indicated or neuropsy-
chiatric syndromes • Phonological speech disorders (speech sound
disorder): Difficulties related to motor pro-
Management duction of speech
• Educational interventions: Social, communi- • Stuttering: Disturbance in the flow of speech
cative, and cognitive skills
• Behavioral modifications, e.g., applied behav-
ioral analysis Language Disorders
• Rehabilitative (occupational and physical
therapy) • Persistent difficulties in acquisition and use
• Referral to early childhood intervention (ECI) of language across different modalities (spo-
in children less than 3 years of age ken, written, or other)
• Referral to local school district in children • Receptive language disorder
3 years and older for evaluation • Expressive language disorder
• Pharmacotherapy: • Mixed receptive–expressive language
–– Risperidone and aripiprazole are approved disorder
by the US Food and Drug Administration
(FDA) for treating associated aggression
–– Other drugs, e.g., selective serotonin reup- Social Communication Disorder
take inhibitors (SSRIs) for anxiety, and
medications used to treat ADHD symptoms • Persistent difficulties in the social use of ver-
bal and nonverbal communication
Prognosis
• The better the language skills and IQ, the bet- Screening
ter the prognosis • Formal audiology evaluation should be done
• Early detection and providing intensive ser- to determine if hearing loss is a cause or
vices improve the outcome contributor.
• Delayed diagnosis may lead to a poorer • Psychoeducational testing: To test specific
outcome learning difficulties
• Neuropsychological testing: To test cognitive
functions
Sensory Over-Responsivity • IQ testing
• Addressing the language difficulties
• Exaggerated behavioral responses to sensory
stimuli Management
• Usually associated with various developmen- • Individual or small group therapy adminis-
tal and behavioral impairments tered by a certified language pathologist
• Possibly comorbid with autism, anxiety dis- • Psychiatric and psychoeducational interven-
orders, and ADHD tions as indicated
• Parent management training/family coaching • For hearing impaired children, three educa-
and referral to occupational therapy might be tional/communication methods are com-
helpful monly used:
170 M. H. Ataalla
–– Oral communication method: uses the Earlier signs of LD may assist in earlier
child’s residual hearing, speech, and lip- identification
reading to develop spoken language • Children with preschool speech and language
–– Manual communication method: uses sign- disorder may later experience educational
ing and fingerspelling difficulty; for example difficulty in recogniz-
–– Sign language: uses hand and body move- ing and drawing of shapes in the preschool
ments and facial expressions to fully period may portend problems in letter recog-
express ideas nition or writing
• Performance of formal developmental screen-
ing at the 30-month visit may identify these
LEARNING DISORDERS related preschool problems
• Performance at the 48-month visit may iden-
Specific Learning Disabilities (LD) tify specific problems in early decoding, writ-
ing, and sound/symbol association
Diagnosed based on one of two criteria:
Associated conditions
1. Aptitude–achievement discrepancy: • ADHD
Discrepancy between IQ level and unexpected • Disruptive behavior disorder
school failure in one or more of school subjects • Anxiety and depression
2. Failure to respond to treatment intervention tar- • Educational underachievement
geting areas of academic weakness • Employment difficulties
• Reading disorders: Difficulties with reading
accuracy and decoding (dyslexia), spelling Screening
difficulties, and/or difficulties with reading • Psychoeducational testing: To test specific
comprehension learning difficulties, usually done at school
• Mathematics (dyscalculia): Difficulties with • Neuropsychological testing: To test cognitive
computation or mathematics that requires functions
problem-solving • IQ testing
• Written expression (dysgraphia), nonverbal
learning disorders, and learning disorders not Management
otherwise specified • Special education service (individualized
education program by school system)
• Primary prevention: High-level education for
Learning Disorder = Learning all children
Disability • Secondary prevention: Interventions directed
to children with academic difficulties not
• Etiology: Intrinsic and extrinsic factors responding to primary prevention
affecting brain maturation and function • Tertiary prevention: Advanced and intensive
• More in boys than in girls services to those who continue to have diffi-
• Underrepresented in minorities culties despite initial interventions provided
• Majority of cases identified in middle and • The US Individuals with Disabilities
high school Education Act requires that special educa-
tion services be provided in the least restric- • Poor school performance can cause low self-
tive environment (students are not to be esteem or even depression
removed from regular classes as much as
possible) Causes
• Treat associated comorbidities if any • Medical problems, e.g.,
–– Malnutrition
Practical issues in the management of learning –– Chronic iron deficiency anemia
disorder –– Worm infestations
• The pediatric clinician can play a critical role –– Preterm or low birth weight
not only in identifying the child with LD, but –– Hearing impairment
also in the ongoing management. ◦◦ Otitis media with effusion and associ-
• The pediatrician or pediatric nurse practitio- ated conductive loss is associated with
ner should inquire about every child’s aca- lower scores in math and expressive lan-
demic performance and school behavior guage between kindergarten and second
• Implementation of the medical home model grade
for chronic condition management ◦◦ Mild sensorineural hearing loss is asso-
• Psychoeducational evaluation with the family ciated with difficulty in multiple educa-
to ensure that he or she is receiving appropri- tional and functional test measures in
ate educational remediation, accommoda- school-aged children
tions, modifications, and therapies –– Visual impairment
• Investigation for related disorders, such as ◦◦ Amblyopia or other refractive disorders
ADHD, adjustment disorder, or anxiety dis- if left uncorrected may harm school
order, should be considered performance
• Education of families is also critically impor- –– Asthma and allergic rhinitis
tant to help them access appropriate ◦◦ Children with poorly controlled asthma
treatment have increased school absenteeism
• Example on family education: At a minimum, –– Obstructive sleep apnea
families should leave the physician’s office ◦◦ May present with ADHD-like symptoms
understanding that reading disorder is not due and poor school performance
to a primary visual deficit and that letter • Below-average intelligence
reversals, a common finding in a typically • Specific learning disability
developing 7-year-old, is not diagnostic of • ADHD
reading disorder • Emotional problems
• Poor sociocultural home environment
• Psychiatric disorders
Poor School Performance [1]
Management
Background • Identify and treat the underlying causes
• Education is critical for human resource • Referral of children with hearing impairment
development to otolaryngologist or audiologist for treating
• Poor academic achievement should be con- the underlying cause of hearing loss
sidered a symptom reflecting an underlying • Referral of children with visual impairment
problem in children to a pediatric ophthalmologist for treating
refractive disorders
172 M. H. Ataalla
Attention-Deficit/Hyperactivity • Impairment is not only academic but also

Disorders (ADHD) behavioral (more in preschoolers), interper-
sonal, and psychological, e.g., low
Background self-esteem
• ADHD is often underdiagnosed; however, it
could also be overestimated Associated conditions
• More prevalent in males • Comorbid psychiatric diagnosis: Oppositional
• Distractibility in preschoolers is difficult to defiant disorder (ODD), conduct disorder
differentiate from inattentive symptoms of (CD), learning disabilities, and anxiety
ADHD disorders
• Expect to find more hyperactive symptoms in
Screening and rating scales
preschoolers, combined ADHD symptoms in
• Diagnosis is made through careful history
elementary students, and more inattentive
(e.g., family history) and clinical interview
symptoms in middle and high graders
• Child with ADHD may not manifest symp-
• Not a single cause but multiple risk factors:
toms in the office setting
Genetics, pregnancy, birth complications, and
• Rating scales are useful to assess the symp-
brain injury
toms, e.g., the Vanderbilt ADHD Rating
• Multiple neurotransmitters involved, particu-
Scales and the Conners Comprehensive
larly dopamine and norepinephrine
Behavior Rating Scales (CBRS)
• Multiple brain regions are affected, particu-
• As needed, physical examination and labora-
larly the prefrontal lobe and the basal
tory tests to work up differential diagnosis
ganglia
• Psychoeducational testing if specific learning
Diagnostic criteria disorder is suspected
• Two groups of symptoms: Inattentive and • IQ and other neuropsychological testing (e.g.,
hyperactive/impulsive continuous performance test) are not rou-
• Three subtypes of the disorder: Predominantly tinely ordered unless indicated
inattentive, predominantly hyperactive/
Differential diagnoses (Tables 6.2 and 6.3)
impulsive, and combined presentation
• Medical illness that may affect a child’s atten-
• For each subtype, must have at least six symp-
tion: Headaches, seizures, allergies, hemato-
toms from the corresponding group, lasting at
logic and endocrine disorders, childhood
least 6 months
cancer
• Symptoms should be out of normal develop-
• Medications, e.g., for asthma, steroids, anti-
mental level, associated with impairment, and
convulsants, and antihistamines
present in two or more settings
• Other psychiatric disorders might present
• Symptoms were present before the age of
with inattention, restlessness, and poor orga-
12 years according to DSM-5 (changed from
nization, e.g., depression and anxiety
7 years old in DSM-IV)
disorders
• Symptoms are not manifestations of another
• Sleep disorders, e.g., obstructive sleep apnea
psychiatric disorder, e.g., depression or
• Substance abuse
anxiety
Table 6.2 Diagnostic symptoms of attention-deficit/hyperactivity disorder (ADHD)

Inattention symptoms Hyperactivity and impulsive symptoms
Often fails to give close attention to details or makes careless Often fidgets with or taps hands or feet; squirms in seat
mistakes in schoolwork or during other activities
Often has difficulty sustaining attention in tasks or play Often leaves seat in situations when remaining seated is
activities expected
Often does not seem to listen when spoken to directly Often runs about or climbs in situations where it is
inappropriate
Often does not follow through on instructions and fails to Often unable to play or engage in leisure activities quietly
finish schoolwork or chores
Often has difficulty organizing tasks and activities Often “on the go,” acting as if “driven by a motor”
Often avoids, dislikes, or is reluctant to engage in tasks that Often talks excessively
require sustained mental effort
Often loses things necessary for tasks or activities Often blurts out an answer before a question has been
completed
Often easily distracted by extraneous stimuli Often has difficulty waiting his or her turn
Often forgetful in daily activities Often interrupts or intrudes on others
Table 6.3 Conditions to be ruled out that may give the picture of attention-
deficit/hyperactivity disorder (ADHD)
symptoms
Environmental conditions Other neuropsychiatric conditions Medical conditions
Cases of physical or sexual abuse Fragile X syndrome Obstructive sleep apnea
Thyroid disorders
Cases of inappropriate parenting practice Fetal alcohol syndrome Heavy metal poisoning
Cases of parental psychopathology Pervasive developmental disorders Medication side effects
Inappropriate classroom setting Anxiety disorders Effects of abused substances
Tourette’s syndrome Sensory deficits
Attachment disorder Auditory and visual processing
disorders
Post-traumatic stress syndrome Neurodegenerative disorder
Post-traumatic head injury
Management • Start medication treatment with a stimulant

• Treatment should be comprehensively (highly efficacious), either from the methyl-
planned: Medications and educational and/or phenidate or amphetamine group (Table 6.4)
behavior therapy • Increase gradually over weeks with frequent
• Psychosocial treatments: Psychoeducation monitoring until symptoms are controlled or
and parent training in behavioral side effects develop
management • Side effects: Decreased appetite (weight
• Educational: Provide school services through monitoring), insomnia, anxiety, tics, and
Section 504 (a part of the US Rehabilitation headaches (Table 6.5 [2])
Act of 1973 that prohibits discrimination • Cardiac: If significant cardiac history in the
based upon disability) or under individual- family, consider electrocardiogram (EKG)
ized educational plan. Address comorbid • Cardiovascular risks and risk of abuse and
learning disorders if any dependence are black box warnings for stim-
• Stimulants are more effective than providing ulant medications. (However, treating ADHD
behavioral treatments alone reduces risk of drug abuse)
174 M. H. Ataalla
Table 6.4 Medications for treatment of attention-deficit/hyperactivity disorder (ADHD)

Duration of
action (in Time to peak in blood (hours
Brand name hours) after the dose) Dosage range Side effects
Methylphenidate immediate release (generic name)
Ritalin 4 1–3 5, 10, 20 mg tabs Appetite suppression
Methylin SOL 4 1–2 5 mg/5 ML, Insomnia
10 mg/5 ML Transient weight loss
Irritability
Emergence of tics
Methylphenidate extended release (generic name)
Metadate ER 4–6 10, 20 mg extended- Same as above
release tabs
Methylin ER 4–6
Concerta 10–12 Initial peak at 1 h and max 18, 27, 36, 54 mg
peak at 7 caps
Ritalin LA 8–10 1st peak 1–3 10, 20, 30, 40 mg
2nd peak 6.5 caps
Metadate CD 8–10 1st peak 1.5 10, 20, 30 mg
2nd peak 4.5 extended-release caps
Quillivant XR SUSP 12 1 h From 4 to 12 ml
25 mg/5 ml (20–60 mg)
Methylphenidate sustained-release (generic name)
Ritalin SR 4–6 4.7 20 mg sustained- Same as above
release tabs
Methylphenidate SR ≥ 12 8–10 10 mg/9 h, 15 mg/9 h, Same as above
20 mg/9 h, 30 mg/9 h
Transdermal methylphenidate (generic name)
Daytrana patch Long-acting Apply 2 h before desired 10, 15, 20, 30 mg Erythema especially when
effect; remove after 9 h (may transdermal patch patch not removed after
remove earlier) 9 h
Dexmethylphenidate (generic name)
Focalin 4 1–1.5 2.5, 5, and 10 mg tabs Same as above
Focalin XR Up to 12 1st peak 1.5 5, 10, 15, 20, 25, 30,
2nd peak 4.5 35, 40 mg
Mixed amphetamine salts (generic name)
Adderall 4–6 3 5, 10, 20 mg tabs Same as above
Adderall XR 8–12 7 5, 10, 15, 20, 25,
30 mg caps
Dextroamphetamine (generic name)
Dexedrine 4–6 3 5, 10, and 15 mg tabs Same as above
Dexedrine spansule 6–8 5, 10, and 20 mg tabs
Lisdexamfetamine (generic name)
Vyvanse ≤ 12 1 30, 50, and 70 mg Same as above
tablets
Amphetamine suspension (generic name)
Dyanavel XR 2.5 mg/ 13 1 h From 1 to 8 ml Same as above
ml
Atomoxetine (generic name)
Strattera Long-acting Weeks 10, 18, 25, 40, 60 mg Dry mouth
caps Nervousness
Fatigue
Dizziness
Dry mouth
Severe liver injury (rare)
Suicidal ideation (rare)
Table 6.4 (continued)
Duration of
action (in Time to peak in blood (hours
Brand name hours) after the dose) Dosage range Side effects
α2-adrenergic agonists
Catapres (clonidine) 8–12 3–5 0.1, 0.2, 0.3 mg tabs Sedation
Depression
Dry mouth
Rebound hypertension on
discontinuing the
medicine
Confusion
Kapvay (clonidine, Long-acting 0.1 mg Same as above
extended release)
Intuniv ER 13–14 1–4 1, 2, 3, 4 mg tabs Hypotension
(guanfacine) Light-headedness
Table 6.5 Management of common side effects of attention-deficit/hyperactivity disorder (ADHD) medications [2]
Methylphenidate/amphetamine derivatives common side
effects Management
Loss of appetite, abdominal pain, headaches, irritability, May be lessened if the medication is taken with food
and sleep problems
Rebound (irritability, increased activity, or mood swings) Administering a low dose of an immediate-release (short-
when medicine wears off acting) stimulant at this time may be helpful
Social withdrawal and lethargy May be lessened by lowering the dose
Weight loss Cyproheptadine may be helpful if weight and appetite loss
are significant
Tics. (Stimulants are not believed to cause tics, but they The presence of tics is not a contraindication to stimulant use
may lower the threshold for the development of tics)
Sudden cardiac death Before using stimulants, refer to a pediatric cardiologist if
preexisting cardiovascular disease or symptoms suggesting
cardiovascular disease
• Contraindications: Glaucoma, uncontrolled • Behavioral techniques for ADHD [2]

seizures, or cardiac disease or active drug –– Positive reinforcement, e.g., rewards or
abuse privileges for desired behaviors
• Atomoxetine (non-stimulant) can be used if –– Time-out, e.g., removal of access to enjoy-
the first and second trial of stimulants fail. able activities or loss of privilege for cer-
Has less effect on sleep and appetite. Can tain time
help with anxiety symptoms if any. Little risk –– Response cost, e.g., withdrawing rewards
of suicidal thinking reported (Table 6.6) or privileges because of undesired behav-
• Guanfacine extended release (Intuniv) is ior or action
approved to treat ADHD (age 6 years and –– Token economy, e.g., child earns points
older). May cause hypotension or sedation (stars, chips, or tickets), for completing
• Refer to specialist if treatment fails or in case certain work or activities or loses stars for
of other psychiatric comorbidities undesired action or behavior; then child
• ADHD medications do not cause tics but may cashes the sum of points at the end of the
make it more obvious week for a prize
176 M. H. Ataalla
Table 6.6 Adverse effects of non-stimulant ADHD Prognosis

medications • ADHD symptoms may continue into adult-
Non-stimulant hood in 60% of cases
ADHD • Untreated ADHD: Risk of criminal behavior,
medications Adverse effects Comment
accidents, employment and marital difficul-
Atomoxetine Decreased appetite, (Long half-life)
abdominal pain, steady-state not ties; more likely to have teen pregnancies
nausea, and reached for up to
somnolence 6 weeks
Less common: DISRUPTIVE, IMPULSE-
headaches, fatigue,
dyspepsia, CONTROL, AND CONDUCT
vomiting, and DISORDERS
diarrhea
Hepatitis (rare and
Background
reversible)
Clonidine Dry mouth, Can be helpful in • All children are defiant at times; such behav-
(α2-adrenergic somnolence, treating ior is a normal part of adolescence
agonists) dizziness, hyperactivity, tics, • Normal stubbornness (3 years), defiance and
hypotension, and or delayed sleep temper tantrums (4–5 years), and argumenta-
constipation onset
tive (6 years)
Guanfacine Dry mouth,
somnolence, • Most disruptive symptoms peak between 8
dizziness, and and 11 years
constipation • Disorder may be present if the behaviors
ADHD Attention-deficit/hyperactivity disorder interfere with family life, school, or peer rela-
tionships or put the child or others in danger
• 5% of children between 6 and 18 years meet
Administration of medications to children who the diagnosis of ODD or CD
may have difficulty with swallowing capsules
and tablets
• Long-acting tablets (e.g., Concerta, methyl- Oppositional Defiant Disorder (ODD)
phenidate tablets) should be swallowed
whole; it cannot be crushed or chewed • Persistent pattern of angry outbursts, arguing,
• Capsules: May sprinkle the contents on apple- and disobedience to authority figures (such as
sauce; swallow without chewing the beads parents and teachers)
• Vyvanse (lisdexamfetamine): May sprinkle –– Often loses temper
contents in a glass of water; needs to be con- –– Often argues with adults
sumed immediately –– Often actively defies or refuses to comply
• Liquid forms of stimulant medications: Short with adults’ requests or rules
(Methylin) and long acting (Quillivant XR, –– Often deliberately annoys people
Dyanavel XR) –– Often blames others for his or her mistakes
or misbehavior
Prevention –– Often moody or easily annoyed by others
• Earlier detection, diagnosis, and treatment –– Often angry and resentful
• Parent training –– Often spiteful or vindictive
Conduct Disorder (CD) Prevention

• Educate the community and target high-risk
• Persistent pattern of serious rule-breaking populations
behavior and violating others’ rights with • Teach parents and teachers effective behavior
lack of guilt: management skills
–– Often bullies, threatens, or intimidates • Child-focused social–emotional skills
others training
–– Often initiates physical fights
–– Has used a weapon that could cause seri- Prognosis
ous physical harm to others • The earlier the onset, the worse the
–– Physical cruelty to people or animals prognosis
–– Stealing while confronting a victim • Comorbidity with ADHD worsens the
–– Forcing someone into sexual activity diagnosis
• 65% of children with ODD will not have the
Associated conditions diagnosis in 3-year follow-up. 30% will prog-
• CD versus ODD: In ODD, there is absence of ress to CD
severe physical aggression and antisocial • CD may continue as antisocial personality
behavior disorder into adulthood
• ADHD • Other psychiatric comorbidities in adulthood
• Bipolar disorder • Multiple adverse outcomes: Social, educa-
• Developmental disorders tional, drugs, and legal problems
• Communication disorders
Screening and rating scales ntisocial Behaviors

A
• Routinely, remember to screen for behavioral and Delinquency
problems
• Use rating scales if answer to screening ques- • Etiology is genetic and environmental
tion is positive, e.g., the Pediatric Symptom • Risk factors: Poverty, association with delin-
Checklist (PSC) quent peers, absence of a role model, history
• Significant scoring on rating scale requires of violence, and poor family functioning
referral to mental health specialist
Management • Illegal offenses and acts
• ODD: Parent management training directed • Examples: Stealing, destruction of property,
to the child’s caregivers. Social–emotional threatening or assault behaviors to people or
skills training directed to the child animals, driving without a license, prostitu-
• CD: Multisystem therapy tion, rape
• Pharmacotherapy used to address comorbidi- • Associated signs: Poor school performance,
ties, e.g., SSRIs, stimulants, mood stabilizers, truancy, poor self-esteem, and low frustration
and antipsychotics tolerance
• Intractable conduct disorder may need resi- • Signs and symptoms of disruptive behavior
dential or specialized foster care treatment disorder or other psychiatric comorbidities
178 M. H. Ataalla
Associated conditions AGGRESSION

• ADHD
• Mood disturbances, e.g., depression • Not every oppositional behavior is an aggres-
• Anxiety disorder sive disorder, unless aggression is pervasive
• Psychotic disorder and out of control
• Etiology: Genetic tendencies; prenatal expo-
Screening and rating scales sure to substances including cocaine, alcohol,
• Rating scales to screen for associated condi- and tobacco; and environmental factors
tions, e.g., Conners for ADHD • A difficult temperament and later aggressive-
• FISTS mnemonic: ness are related. More in boys
–– F: Fighting (How many fights were you in • History of abuse, neglect, or abandonment
last year? What was the last?) and inconsistent discipline
–– I: Injuries (Have you ever been injured? • Corporal punishment in children: Stimulates
Have you ever injured someone else?) anger and teaches that violence is an accept-
–– S: Sex (Has your partner hit you? Have you able way of solving problems
hit your partner? Have you ever been forced • Later in adulthood: Childhood aggression is
to have sex?) positively associated with aggression, crimi-
–– T: Threats (Has someone with a weapon nal and antisocial behavior, and adult abuse
threatened you? What happened? Has any- of one’s own child or spouse
thing changed to make you feel safer?) • Violence in the media: Desensitizes children
–– S: Self-defense (What do you do if some- to violence; may lead to aggressive and anti-
one tries to pick a fight? Have you carried social behaviors
a weapon in self-defense?)
Management • Aggression: Reactive/affective aggression vs.
• Evaluation: Comprehensive biopsychosocial proactive unemotional aggression. Direct
approach versus indirect aggression
• Multisystemic treatment • Temper tantrums: Common during the first
• Family involvement is important: Family few years of life
therapy and parent management training • Biting:
• Cognitive behavioral therapy (CBT) –– Toddlers may bite to communicate frustra-
• Pharmacotherapy and appropriate referrals tion or when they experience a stressful
for associated conditions event
–– Preschoolers: Occasional or rare biting to
Prevention
exert control over a situation, for attention,
• Individual approaches, e.g., teaching coping
as a self-defense, or out of extreme frustra-
strategies
tion and anger
• Relationship approaches: Focus more on
–– After age of 3 years, frequent biting may
family and peer relationships
indicate a behavioral problem or sensory
• Community-based approaches: Community
integration dysfunction
education
• Breath-holding spells: Sign of frustration and
• Societal approaches: Through advocacy and
emotional distress
legislative actions
• Bullying • Breath-holding spells: Advise the parents to

• Lying: In young children can be a way to intervene before emotional escalation. Help
express fantasy, to explore with language, or the child to calm down by offering 2–3 min
to avoid consequences. In school-aged chil- time-out
dren and adolescents, chronic lying is a • Truancy and running away: Always assess
problem and address the underlying problem
• Stealing: Preschoolers and school-aged chil- • Stealing: Behavioral modification and teach
dren may steal more than once or twice. the child better coping skills
Requires evaluation when it becomes a • Lying: Educate the child that lying is unac-
pattern ceptable. Provide support and set limits
• Truancy and running away • Fire setting always requires intervention by
• Fire setting: Unsupervised fire setting is mental health specialist
always inappropriate
Associated conditions Bullying [3]

• ADHD
• ODD and/or CD Background
• Depression and bipolar disorder • Bullying is a form of aggression in which one
• Developmental disorders or more children repeatedly and intentionally
intimidate, harass, or physically harm a vic-
Screening and rating scales tim who is perceived as unable to defend him-
• Child Behavior Checklist and Overt self or herself
Aggression Scale • School can be unfriendly and dangerous place
• Other rating scales to rule out associated con- for bullied children
ditions, e.g., Conners for ADHD, IQ testing
Consequences of bullying
Management • Fear
• Early interventions for severe cases • Permanent anxiety
• Need to address any biological, psychiatric, • Insecurity
or somatic disorders while controlling for • Depression
environmental triggers • Low self-esteem
• Pharmacotherapy for associated conditions, • Chronic absenteeism
e.g., stimulants to treat ADHD • Drop in grades
• Need to involve school and family members
to provide collateral information and to par- Role of the pediatrician
ticipate in the treatment plan • Identifying the problem
• Refer to mental health intervention: Those • Counseling parents, children, and perhaps
who show no empathy or remorse and those school personnel regarding intervention and
with severe comorbidities prevention
• Temper tantrums: Time-out and discuss the • Screening for, treating, or referring to psy-
reason of frustration when the child calms chiatrists or psychologists when mental
down comorbidities are present
180 M. H. Ataalla
• Advocating for violence prevention and for Separation anxiety disorder

the right of children to attend school and • Separation anxiety is developmentally nor-
live free of threat of violence by other mal in infants and toddlers until approxi-
children mately age 3–4 years
• Separation anxiety disorder: Symptoms usu-
ally present after the age of 6 years
ANXIETY DISORDERS • Symptoms should present for at least 4 weeks
to make the diagnosis
Background • Excess distress due to fear of separation from
• Common psychiatric disorder in children attachment figure
• Females may report anxiety disorder more • Excess worrying about own or parent’s safety
than males • Nightmares with themes of separation,
• Multiple risk factors somatic complaints, and school refusal
• Genetics: Parents with anxiety disorder
• Temperamental style: Inhibited Specific phobia
• Parenting styles: Overprotective, overcon- • Marked and persistent fear of a particular
trolling, and overly critical object or situation that is avoided or endured
• Insecure attachment relationships with care- with great distress, e.g., fear of animals or
givers: Anxious/resistant attachment injections
• Five categories: Animal, natural environment,
Common developmental fears (Table 6.7) blood injection, situational (e.g., flying), and
• Separation anxiety (decreases with age) others
• Fear of loud noises and strangers (common in
infants) Generalized anxiety disorders
• Fear of imaginative creature and darkness • Chronic, excessive worry in a number of
(common in toddler) areas such as schoolwork, social interactions,
• Fear of injuries or natural events (e.g., storms) family, health/safety, world events, and natu-
• Worries about school performance, social ral disasters with at least one associated
competence, and health issues (children and somatic symptoms for at least 6 months
adolescents)
• Fears and worries become disorder when they Social phobia
are impairing and if they do not resolve with • Feeling scared or uncomfortable in one or
time more social settings (discomfort with unfa-
• Anxious child may present with somatic miliar peers and not just unfamiliar adults) or
complaints (headache and stomachache) or performance situations
disruptive behaviors (defiance, anger, crying,
and irritability) while trying to avoid anxiety- Selective mutism
provoking stimuli • Persistent failure to speak, read aloud, or sing
in specific situations (e.g., school) despite
Table 6.7 Difference between fears and phobia speaking in other situations (e.g., with
Fears Phobia family)
Fears may be Excess fears
appropriate to age Panic disorder
Child can overcome the Associated with impairment in • Recurrent episodes of intense fear that occur
fear some cases unexpectedly
• Associated with at least 4 of 13 autonomic O bsessive Compulsive Disorders

anxiety symptoms such as pounding heart, (OCD)
sweating, shaking, difficulty breathing, and
chest pain • Prevalence is between 0.2% and 1.2% with
equal sex distributions
Associated conditions • Etiology is strongly genetic
• Depression
• Externalizing behaviors disorders, e.g., ODD Clinical presentation
• ADHD • Common obsessions in adolescents: Dirt and
• Selective mutism germs, relationship problems, exactness,
• School refusal symmetry, religious themes
• Common compulsions: Cleaning rituals,
Screening and rating scales repeating rituals (doing and undoing), check-
• Multidimensional Anxiety Scale for Children ing rituals
(MASC) • Remember to ask about the family’s reaction
• Screen for Child Anxiety-Related Emotional to the child’s OCD behavior
Disorders (SCARED)
Management • Tic disorder, major depression, and specific
• Provide education, e.g., educate parents that developmental disabilities
phobias are not unusual and are not associ- –– Pediatric autoimmune neuropsychiatric dis-
ated with impairment in most cases orders associated with streptococcal infec-
• Combined psychotherapy and pharmacother- tion (PANDAS). Condition reported in some
apy are most effective cases of sudden-onset OCD and tics. The
• Psychotherapy (could be offered alone in validity of this diagnosis is controversial
mild anxiety cases)
–– Cognitive behavioral therapy (CBT) Screening and rating scale
–– Specific phobias: Graded exposure and sys- • Yale–Brown Obsessive Compulsive Scale
tematic desensitization (CY-BOCS)
–– Selective mutism: Behavioral therapy
–– Parent–child and family intervention Therapy or management or treatment
–– Psychodynamic psychotherapy for selected • Treat with cognitive behavioral therapy
adolescent cases (CBT). Add medications for moderate to
• Pharmacotherapy: SSRIs, e.g., fluoxetine and severe cases (Y-BOCS > 21)
sertraline • Four FDA-approved medications for OCD:
• School refusal: Do not advise school leave. –– Tricyclic antidepressants: clomipramine
Treat underlying anxiety as above (Anafranil)
Prognosis –– SSRIs: fluoxetine (Prozac), sertraline
• Pediatric generalized anxiety disorder is asso- (Zoloft), paroxetine (Paxil), fluvoxamine
ciated with adulthood anxiety and major (Luvox)
depression disorder • Family education: Refer to the OCD
• Pediatric separation anxiety disorder may be Foundation website resource section at http://
associated with panic disorder in adulthood www.ocfoundation.org
182 M. H. Ataalla
TRAUMA- AND STRESSOR- –– SSRIs can be helpful in dealing with the core

symptoms (including anxiety, depression,
RELATED DISORDERS withdrawal, and avoidance)
• Acute stress disorder
• Adjustment disorders
ost-Traumatic Stress Disorder
P
• Post-traumatic stress disorder (PTSD)
• Reactive attachment disorder (PTSD)
• Disinhibited social engagement disorder
• Persistent pattern of avoidance behavior,
flashbacks, and emotional distress that lasts
Acute Stress Disorder 6 months after exposure to severe distress or
trauma
Background • In DSM-5, PTSD is listed under “Trauma-
• Acute stress due to exposure to actual or and Stressor-Related Disorders.” It is no lon-
threatened death, serious injury, or sexual ger listed under “Anxiety Disorders”
violation
• Witnessing violent/traumatic loss of loved one, Management
death of one parent, grandparent, or a sibling • Trauma-focused cognitive behavioral therapy
(TFCBT)
Clinical presentation • SSRIs are considered the medications of
• Recurrent, involuntary, and intrusive distress- choice for managing anxiety, depression,
ing memories of the traumatic event avoidance behavior, and intrusive
• Recurrent distressing dreams recollections
• Dissociative reactions (e.g., flashbacks) in • Consultation with therapists and child psy-
which the child feels or acts as if the trau- chiatrists with expertise in the treatment of
matic event(s) were recurring PTSD in children is generally warranted
• Sleep disturbance (e.g., difficulty falling or
staying asleep or restlessness during sleep)
• Difficulty with concentration Reactive Attachment Disorder
• Exaggerated startle response
• A consistent pattern of inhibited, emotionally
Diagnosis withdrawn behavior toward adult caregivers
• Duration of the disturbance is 3 days to in a child more than 9 months and less than
1 month after trauma exposure 5 years, e.g., a child who rarely or minimally
• Fulfill the diagnostic criteria (DSM-5) for seeks comfort when distressed
acute stress disorder (ASD)
Management
• Reduce stress
isinhibited Social Disengagement
D
• Provide support Disorder
• Promote coping mechanisms
• A pattern of behavior in which a child actively
• Avoid increasing stress
approaches and interacts with unfamiliar
• Psychological and behavioral intervention
adults in an impulsive, incautious, and over-
• Pharmacotherapy, e.g.,
familiar way, e.g., a child willing to approach
–– Beta-blockers may limit hyperarousal symp-
a stranger for food, to be picked up, or to
toms, both initially and over the longer term
receive a toy
–– Diphenhydramine and other medications
may be helpful for improving sleep
• The child has a developmental age of at least

9 months
Adjustment Disorders
Background
• Adjustment disorder is a stress-related, short-
term, nonpsychotic disturbance Fig. 6.1 Child with loss of upper eyelid lashes due to
trichotillomania
• Depressed/irritable mood Teeth grinding (bruxism)
• Sadness • Common behavior
• Anxiety • When persists, it may be a manifestation of
• Sleep disturbances anxiety
• Poor concentration • May cause dental problems that need to be
• Poor performance in school addressed by appropriate dental referral
• Anger, disruptive behavior • Dental occlusal splints are occasionally used
• Loss of self-esteem in the treatment of oral destructive habits
• Hopelessness • Nocturnal biofeedback
• Feeling isolated or cut off from others
Thumb-sucking
Diagnosis • Few studies advocating thumb-sucking as a
• Emotional or behavioral symptoms occur preventive measure against sudden infant
after an identifiable stressor or stressors death syndrome (SIDS)
within 3 months of the onset of the stressor • The incidence of thumb-sucking among chil-
• Marked distress that is out of proportion to dren decreases with age: Onset during the
the severity or intensity of the stressor first few months and peak at 18–21 months
• Significant impairment in social, occupa- • Self-soothing behavior that is normal in
tional, or other areas of functioning infants and toddlers
• Not related to other mental disorders • Management
• Symptoms do not represent normal bereavement –– Most children spontaneously stop thumb-
• Symptoms persist for no longer than an addi- sucking between 2 and 4 years of age
tional 6 months –– School-aged children with persistent
thumb- sucking should be referred to a
Management pediatric dentist
• Brief psychotherapy –– Prolonged thumb-sucking can affect a
child’s teeth alignment and mouth shape
–– If persistent, behavioral evaluation is
HABIT DISORDERS necessary
–– Usually, treatment is required in severe
Trichotillomania (hair-pulling disorder) cases, e.g., if continued beyond age
(Fig. 6.1) 4–5 years, dental problems, increased risk
• Repeated behavior of hair pulling to the of accidental ingestions and pica, thumb
extent of hair loss, associated with increased calluses and skin breakdown, deformities
tension prior to hair pulling and relief during of the fingers and thumbs, and paronychia
and after it
184 M. H. Ataalla
–– Gloves or adhesive plasters can remove the M ajor Depression

antecedent stimulus for thumb-sucking
–– Have the child fold his or her arms when Background
the stereotypy occurs • More common in adolescents than in
children
Head banging • Male–female ratio of 1:1 during childhood
• Not always a manifestation of autistic and 1:2 during adolescence
disorder • Highly familial disorder with both genetic
• Helmets may be required for children with and environmental influences
severe and persistent head banging, espe-
cially in children with intellectual disability Risk factors
• Parental psychopathology, impaired parent-
Nail biting ing, loss of a parent
• In excess can manifest anxiety • Lack of social support
• Exposure to domestic and community
General management of habit disorders violence
• Educate parents that the habit may resolve if • Low socioeconomic status
ignored • Physical and sexual abuse and neglect usually
• Treatment is indicated if impairment is increase the risk of depression
associated • Chronic medical conditions
• Behavioral therapy is the main line of treat-
ment, e.g., habit reversal and relaxation train- Diagnostic criteria
ing (e.g., breathing exercises) • At least 2 weeks in which mood is depressed
• Trichotillomania: CBT psychotherapy is or irritable and/or loss of interest or pleasure
superior to medication treatment, e.g., SSRIs in nearly all activities (anhedonic mood)
and clomipramine • The symptoms should be present for most of
• Need to explore and treat comorbidities, e.g., the day, nearly every day
developmental disorders, anxiety, and depres- • Associated vegetative and cognitive symp-
sive disorders toms, including disturbances in appetite,
• Remember not to confuse habit-forming dis- sleep, and energy; impaired concentration;
order with tic disorder/Tourette syndrome and thoughts of worthlessness, guilt, and
• Tic is a sudden, rapid, recurrent, nonrhythmic, suicide
stereotyped motor movement or vocalization • To meet the syndromal diagnosis: Need to
have abnormal mood plus four or more of
associated symptoms
MOOD AND AFFECT • These symptoms are clear change from base-
DISORDERS line and are associated with impairment
• Spectrum disorder with symptoms ranging Differential diagnosis of depressive (and

from subsyndromal to syndromal bipolar) symptoms
• Depressive disorders: Major depression, per- • General medical conditions and medications
sistent depressive disorder, disruptive mood causing mood symptoms
dysregulation disorder, premenstrual dys- • Substance abuse-induced depressive
phoric disorder symptoms
• Bipolar-related disorders: Bipolar I disorder, • Other psychiatric disorders anxiety, ADHD,
bipolar II disorder, cyclothymic disorder disruptive behavior, developmental disorders
• “Normal ups and downs” of children and • Contact school to provide accommodation
adolescents: Not associated with functional needed. Parent should consent to this
impairment. Not severe and do not last long
enough to be considered an episode Medications
• “Adolescent anhedonia”: Depressive symp- • SSRIs: 50% will respond, and 30% experi-
toms and variability of mood in normal ence symptom remission
adolescents • Start medication low and monitor for side
effects
Associated conditions • FDA approved: Fluoxetine (> 8 years) and
• The most common comorbid diagnosis is escitalopram (> 12 years)
anxiety disorder • Fluoxetine can be started at 5–10 mg daily,
• Other comorbidities include disruptive behav- increasing the dose gradually at 2-week inter-
ior, ADHD, and substance use disorder vals up to a target range of 20–80 mg daily
• Could occur concurrently with dysthymic • Initiating therapy with higher-than-recom-
disorders (double depression) mended doses is associated with increased
self-harm episodes
Screening and rating scales • The most common side effects include irrita-
• Screen all children and adolescents for the bility, gastrointestinal symptoms, sleep dis-
key depressive symptoms: Sadness, irritabil- turbance, restlessness, headaches, and sexual
ity, and anhedonia dysfunction
• Beck Depression Inventory for Primary Care • Rare but serious side effects: Predisposition
(BDI-PC) to bleeding and increased suicidal thoughts
• Children’s Depression Inventory (CDI) • Successful treatment should continue for
• Patient Health Questionnaire for Adolescents 6–12 months
(PHQ-A) • Follow up every 3 months after remission to
• Positive response of depression indicates ask- monitor symptoms and to assess for adverse
ing if any suicidal ideation effects of medication
Management Therapy and prevention

• Family education about the causes, symp- • CBT strategies, e.g., correcting automatic
toms, course, and treatments and the associ- negative attributions
ated risks • Interpersonal therapy for adolescent
• Mild depression: 4–6 weeks of supportive depression
psychotherapy. May not need medication • Lifestyle modifications (e.g., regular and ade-
• Moderate depression: 8–12 weeks of CBT or quate sleep, exercise, and relaxation)
interpersonal therapy. May respond without
need for medication Prognosis
• Severe depression: Combined medication • 60% will suffer suicidal ideation, and 30%
and therapy will attempt suicide
• Recurrent, chronic, or severe major depres- • Rate of recurrence of depression reaches 70%
sion may require longer than 12 months after 5 years
• Refer suicidal, psychotic, and bipolar • 20% of adolescents with major depression
depressed patients to specialized treatment develop bipolar disorder within 5 years of the
• Family involvement: Work on dysfunction onset of depression
and stressors and maximize support • High risk of substance abuse and other psy-
chiatric disorders
186 M. H. Ataalla
• Difficulties with school, peers, and family • The lifetime prevalence of each of the bipolar
• Difficulties adjusting to life stressors; physi- disorders and cyclothymic disorders is about
cal illness 0.6%
• Equal sex distribution
Persistent Depressive Disorder (Dysthymic
Disorders) Diagnostic criteria
• One year of suffering depressed/irritable • In mania: There is one week of persistently
mood plus two or more of the associated veg- elevated, expansive, or irritable mood
etative and cognitive symptoms of • In hypomania: Abnormal mood lasts at least
depression 4 days but less than a week, and the impair-
• Diagnosis requires association with signifi- ment is not as severe
cant distress or impairment • Associated cognitive and behavioral symp-
• If a dysthymic patient develops an episode of toms: Increased energy, grandiosity, reduced
major depression, then both diagnoses may need for sleep, pressured speech, distractibil-
be given (it is also called double depression) ity, racing thoughts, engaging in multiple
activities and tasks, and impulsively doing
Depressive Disorders Not Otherwise Specified things that have the potential for harm in
• (Subsyndromal depression) presence of excess
depressive symptoms that are not enough to
meet full diagnostic criteria for major depres- Associated conditions
sive disorder or dysthymic disorder • Other psychiatric disorders, including ADHD,
anxiety, eating, and substance use disorders
Bipolar Disorders Screening and rating scales

• Screen for the cardinal manic symptoms:
Background Elation and grandiosity, increased energy
• Bipolar disorder type I: One episode of with decreased need for sleep
mania is enough to make the diagnosis. • If screening is positive: Refer to a specialist
Often alternates with episodes of major for comprehensive evaluation
depression • Always remember to assess for risk of harm
• Bipolar disorder type II: Requires one epi- to self or others
sode of major depression that alternates with • Specific instruments:
at least one episode of hypomania but no –– Young Mania Rating Scale (YMRS)
manic episodes –– Schedule for Affective Disorders and
• Bipolar not otherwise specified (subsyndro- Schizophrenia
mal bipolar disorder): Mixture of depressive
and manic symptoms that are not enough to Management of bipolar disorders
diagnose type I or II disorders • Start with psychoeducation. Family and
• Early-onset bipolar disorder may not present school involvement (as in treatment of major
with classic symptoms and distinct mood epi- depression)
sodes. Irritability and increased energy epi- • Be aware of different side effects of the medi-
sodes are commonly present cation used. Need to monitor baseline and
• Cyclothymic disorders: Multiple episodes of follow-up parameters
hypomania and subsyndromal depression for • Medications to treat manic episode: Lithium
at least 1 year FDA-approved (for youth > 13 year) or atypi-
cal antipsychotics (aripiprazole, olanzapine, • Completing suicide: More in males (by fire-
risperidone, quetiapine) arms) than in females (by poisoning)
• Medications to treat bipolar depressive epi- • Attempting suicide: More in females.
sodes: Lurasidone and olanzapine (> 10 years) Ingestion of medication the most common
• Lithium common side effects: Cardiac, renal, method
thyroid, and hematologic effects; toxicity; • Ethnic groups with the highest risk: American
teratogenicity Indians and Alaska Natives
• Valproate (Depakote, AbbVie): Hematologic, • Ethnic groups with the lowest risk: African
hepatic, and ovarian (polycystic ovarian syn- Americans, Hispanics, and Asians
drome); teratogenicity
• Atypical antipsychotics: Weight gain; meta- Risk factors for attempting suicide
bolic (diabetes, hyperlipidemia); cardiac • Suffering psychiatric illness (in most sui-
effects cides): Major depression (most common)
• For comorbid ADHD: May use stimulants • History of self-harming behavior even with
when the mood is stable no explicit intention to die (e.g., self-cutting)
• Psychotherapy needs to be offered to address • Cognitive functioning: Poor self-esteem and
impairment in different domains and provide lack of coping strategies
support to the patient and family • Stressful life events: Academic or relation-
• Refer suicidal and psychotic bipolar depressed ship problems, being bullied, family
patients to psychiatric hospitalization instability
• Newly diagnosed medical condition or a
Prevention recent or anticipated loss
• For those with cyclothymic mood disorder: • Difficulties with sexual orientation and
Adequate mood stabilization may decrease homosexuality
risk for subsequent bipolar disorder • Physical and sexual abuse
development • Suicide of a close person
• Identify and address social and psychological • Suicide by imitation: Exposure to suicide in
stressors that may precipitate mood the media or a book’s hero who commits
decompensation suicide
• Stress of acculturations for the immigrants
Prognosis
• 80% will have recurrences after recovery Risk factors for completed suicide
from the first mood episode • Male gender
• Completed suicide (10–15% of those with • History of suicide attempt
bipolar I disorder) • Having suicidal intent, a written note, or a
• Poor outcome with no treatment: plan
Unemployment and legal problems • Showing acute signs of depression, mania,
and psychosis or substance intoxication
• Lack of family support and supervision to
Suicidal Behaviors maintain safety at home
Background Screening and assessment

• Third leading cause of death among young • Ask about suicidal ideation during routine
people aged 15–24 years visits
• Fourth leading cause of death among young • Ask specifically about suicidal ideation: “It
people aged 10–14 years will not implant the idea in his/her head”
188 M. H. Ataalla
• Obtain collateral information from parents • Residual phase: Several months or more,
and other resources when there are no significant positive
• Psychiatric evaluation of the severity of sui- symptoms
cidality and the risk factors • Auditory hallucinations suggestive of schizo-
phrenia: Commentary voice or multiple
Management voices
• Psychiatric hospitalization for severe suicidal
cases and after attempts Differential diagnosis
• Close outpatient follow up: When risk factors • Hallucinations that are not psychotic: In
for committing suicide are not present and the response to anxiety or stress
patient is able to contract for safety • Affective psychosis
• Post-traumatic stress disorder
Prevention • Autism spectrum disorders
• Remember to screen for suicidal risk • Medical conditions and drug abuse
• Address suicidal risk factors
• Schools and public-based suicide prevention Screening
program • Screen for hallucination during regular
visits
Prognosis • Abnormal Involuntary Movement Scale
• Remember: Even when suicidal intent is (AIMS): Screen and monitor for antipsychot-
ambiguous, an impulsive suicidal act may ics’ extrapyramidal side effects
lead to death
Management
• Psychoeducation
CHILDHOOD SCHIZOPHRENIA • Risk management and case management
services
Background • Educational placement: Specialized educa-
• Schizophrenia is a heterogeneous clinical tional programs should be considered within
syndrome the school system
• Childhood-onset schizophrenia is rare. More • 1st generation antipsychotics are not com-
in males monly used due to high risk of extrapyrami-
• Risk factors, e.g., advanced parental age and dal side effects e.g., haloperidol
genetic (e.g., 22q11 deletion) • 2nd generation antipsychotics are the mainstay
of treatment e.g., risperidone, aripiprazole
Clinical presentation (abilify), or clozapine (for resistant cases)
• Course of illness • Side effects: Metabolic syndrome (obesity,
• Prodrome: Functional deterioration before hypertension, dyslipidemia, and insulin resis-
the onset of psychotic symptoms tance) and extrapyramidal symptoms (e.g.,
• Acute phase: Marked by prominent positive dystonia and akathisia)
symptoms (i.e., hallucinations, delusions, • Clozapine: Increase the risk for agranulocy-
disorganized speech and behavior) and a sig- tosis and seizures
nificant deterioration in functioning
• Recuperative/recovery phase: Generally, a Prognosis
several months period. Negative symptoms • Early-onset schizophrenia is a risk factor for
(flat affect, anergia, social withdrawal) more impairment from the illness
predominate • High risk of suicide
PSYCHOSOMATIC DISORDERS • Teach self-monitoring techniques (e.g., hyp-

nosis, relaxation, and biofeedback), family
• Somatic symptoms disorder: Excess worries and group therapies
about somatic symptoms, longer > 6 months. • Aggressively treat comorbid psychiatric
Prevalence is very common, 10–15% conditions
• Headaches are the most common overall. • Avoid unnecessary workup
Functional abdominal pain is the most com- • CBT and family therapy
mon in preschoolers • Psychiatric consultation
• The symptoms could be a symbolic attempt • Psychopharmacologic interventions as
to resolve unresolved and unconscious con- appropriate
flicts (primary gain)
• Conversion disorder (functional neurological
symptom disorder), e.g., weakness, paralysis, SLEEP DISORDERS
seizures, abnormal movement, or seizures.
Not as common in Western countries Background
• Child with chronic insufficient sleep may
Clinical presentation manifest with difficult learning and irritabil-
• Serious physical illness was ruled out ity or picture of ADHD
• Somatic symptoms and psychosocial stress- • Electrophysiologically, sleep can be divided
ors occurred around the same time into:
• Presence of comorbid psychiatric disorder –– Rapid eye movement (REM) sleep
• Associated conditions: Anxieties, depressive –– Non-rapid eye movement (NREM) sleep
symptoms, substance abuse disorder, inhib-
ited temperament Sleep needs according to age
• The symptoms often result in increased atten- • Newborn: 10–19 h per 24 h
tion for the patient (secondary gain) –– REM sleep occupies 50% of total sleep.
• Any form of stress could contribute to psy- Decreases with age
chosomatic disorders; these include bullying –– Frequent awakening may require attention
and physical or sexual abuse only if > 2–3 awakenings per night > 30 min
• Infant: 12–13 h
Differential diagnosis of conversion symptoms • Toddler: 11–13 h
include • Preschool (3–5 year): nighttime 10–13 h
–– Psychophysiology hypochondriasis • Middle childhood (6–12 year) 9–11 h
–– Malingering • Adolescence (> 12 year) 9 h
–– Somatic delusions
Parental education
Screening and rating scales • Sleep hygiene and behavioral approach to
• Children’s Somatization Inventory (CSI) address behavioral insomnia of childhood,
• Functional Disability Inventory (FDI) e.g., bed routines, avoid overstimulation,
address separation anxiety at bedtime
Management
• Educate parents and provide reassurance in
considerate nonjudgmental way Classifications of Sleep Disorders
• Convey encouragement and support
• Advise to continue with school attendance • Insomnia secondary to another condition,
• Positive reinforcement e.g., medical or psychiatric illness
190 M. H. Ataalla
• Sleep disorders: subdivided into parasomnias Table 6.8 Difference between night terrors and nightmares
and dyssomnias Night terrors Nightmares
Occurs during Non- Occurs during REM
REM sleep
Parasomnias Sudden episode of Recurrent episodes of awakening
crying or loud scream from sleep with recall of an
with intense fear intensely disturbing dream
• Abnormal events upon a normally organized Does not recall the Recall of dream is immediate and
sleep-wake process dream clear
• Includes nightmares, night terrors, sleepwalk- Difficulty in arousing Delayed return to sleep after the
ing, and sleep talking the child episode
Help child to return to Reassure the child it was a bad
sleep dream
Protect the child from
Nightmares injury
REM rapid eye movement
• Occur during REM sleep, commonly after 2
a.m. • Mental confusion when awakened from an
episode; child is inconsolable
• Nightmares usually occur during the second Management
half of REM sleep • Parental and child education and
• Recurrent episodes of awakening from sleep reassurance.
• Recall of an intensely disturbing bad dream • Advise regarding sleep hygiene
• Full alertness on awakening, with little con- • Awaken child 15 min before terrors occur.
fusion or disorientation Avoid overtiredness
• Delayed return to sleep after the episode • Be calm; speak in soft, soothing, repetitive
Management tones; help the child return to sleep
• Reassure the child that he or she had a bad • Protect the child from injury
dream Sleepwalking and sleep talking
• Leave the bedroom door open, use a night- –– Stage 4 NREM sleep events, with no recall in
light, and demonstrate that there are no mon- the morning
sters under the bed. –– Parental education and reassurance
• Discuss dream the following day. –– Secure bedroom surroundings to avoid acci-
• If frequent, need to explore and address the dental injuries to the sleepwalker
source of anxiety.
• Avoid scary movies or TV shows.
Bedtime Refusal/Frequent
Awakening
Night Terrors
• Appropriate management
• Occur during stage 4 NREM sleep, first third –– Quiet routine before bedtime, e.g., story
of the night time, bathing, making the room dark
–– Bedtime should be the same every night
Clinical presentation (Table 6.8)
–– Allow the child to take a favorite belonging
• The child is screaming unresponsive for few
to bed each night, e.g., teddy bear
minutes and then falls back asleep again.
–– Ensure that the child is comfortable, e.g.,
• Will not recollect the episode in the morning
door left slightly open
• Manifestations of intense fear
–– Children should not be allowed to sleep in
• Difficulty in arousing the child, and the child
the same bed with parents
wants to fall asleep soon after the episode
–– Parents not to return to the child’s room Restless leg syndrome

every time he or she complains or calls out, • May be associated with low iron storage that
e.g., give more time before response, could benefit from iron therapy
because the child may fall asleep
–– Keeping the room dark and quiet upon
return to the child’s room Benign Sleep Myoclonus of Infancy
–– The process may take time; negative
response can sometimes make a sleep Background
problem worse • This is a benign disorder that typically
–– Medications, e.g., melatonin can be used in starts in early infancy and resolves over
addition to good sleep hygiene in children 2–3 months
with neurodevelopmental conditions and
sleep disorders
• Jerking movements of the limb(s)
• Occurs when the infant is asleep
Dyssomnias • Arousing the infant stops the movements
• The limb jerking occurs for variable intervals,
• Difficulties initiating and/or maintaining from a few seconds or minutes up to 30 min
sleep • It may move from 1 limb to another and then
back to the first limb
Primary insomnia • There is no alteration in breathing
• After psychiatric disorder is ruled out, sleep
hygiene is the main line of treatment Address Management
emotional concerns and worries in the child • Reassurance
in general
• No TV in the bedroom
• Melatonin can be helpful SEXUAL BEHAVIORS
• Appropriate referral to sleep study for resis-
tant chronic cases Examples of Inappropriate Sexual
Behaviors That May Indicate Sexual
Primary hypersomnia Abuse
• Increased need for daytime sleep despite ade-
quate nighttime sleep • Sexual knowledge inappropriate to age
• Rule out organic causes, e.g., medication side • Heightened sexual interest, e.g., drawing gen-
effects or hypothyroidism itals or asking to engage in sexual act
• If diagnosis is established, may be treated • Masturbating with objects and compulsive
with stimulants masturbation
• Inserting objects in vagina or rectum
Circadian rhythm disorder • Close physical boundaries
• Managed through gradual advance of bed- • Sexual promiscuity and prostitution in
time (15 min per night) adolescence
• For severe cases: Phase delay therapy
• Naps are discouraged during trials to restore
normal circadian rhythms Masturbation
Narcolepsy • During the preschool years: Genital interest
• Characterized by sleep attacks upon wakeful- and play are fairly common
ness and cataplectic attacks
192 M. H. Ataalla
• About 80% of adolescents report masturbat- • Sexually transmitted diseases (STDs)

ing by age of 13 years, more in boys –– Risk in homosexuals is the same as in het-
• Adolescents may experience inappropriate erosexuals if protection is not used.
anxiety and/or guilt related to this However, homosexuals who engage in rec-
behavior tal intercourse may be at higher risk
• Provide information on normal sexual devel- • Recommendations
opment and reassurance –– Explore sexual orientation without hetero-
• Masturbation in public suggests poor aware- sexual assumptions
ness of social reality –– Provide nonjudgmental care or refer
• Masturbation seldom produces self-induced patients to better resources
injury in childhood –– Education and counseling regarding STDs
• Hazards of excessive masturbation: Genital –– Referral to social support groups
itching, sexual overstimulation, environmen-
tal deprivation
ender Dysphoria GD (Gender
G
identity disorder)
Sexual Identity Development
• GD in children: Six or more of cross-gender
• Core gender identity: Basic sense of being behaviors for at least 6 months duration
male or female during toddler or preschool age, e.g., cross-
• Gender role: Expected behaviors from the dressing and preference for playmate of
person related to his/her gender opposite sex
• Social sex role: How the person behaves in • GD in adolescents: Two or more of cross-gen-
congruence/incongruence with the gender der behaviors for at least 6 months duration
role (as in gender nonconformity) • Comorbidities: Pervasive developmental dis-
• Sexual orientation: How the person is orders and externalizing behavioral problems
attracted to the same or the opposite sex. • Treatment: Early onset GD may respond to
Starts around mid-adolescence therapeutic interventions (controversial)
Homosexuality TOILET TRAINING

• 30% of early adolescents may engage in R eadiness for Toilet Training Is
homosexual play once or twice, but it is usu-
ally not persistent
Associated with
• Comorbidities associated with homosexuality • Awareness of bladder filling
1. Social stigma may inflict guilt and anxiety • Ability to contract the external sphincter
on the homosexual teen • Able to indicate wants and needs verbally
2. Disclosure to friends and family may lead • Able to sit on, and rise from, the potty chair
to significant distress and turmoil • Motivation of the child to stay dry
3. Academic complications and dropping out • At 2–4 years, the child is developmentally
due to bullying and lack of support at ready to begin toilet training
school • Girls usually attain bladder control before boys
4. Psychiatric complications, e.g., higher risk • Bowel control typically is achieved before
of suicidal behavior, substance abuse, and bladder control
eating disorders
Delayed Toilet Training Depressant abuse

• Prescription sedatives: Benzodiazepines:
• Delayed toilet training can cause parental alprazolam (Xanax), diazepam (Valium),
frustration and abuse lorazepam (Ativan), 2%
• Some toddlers are ready as early as 18 months, • Prescription tranquilizers: Barbiturates
and some are not ready until beyond third (pentobarbital) and sleep medications: eszop-
birthday iclone (Lunesta), zolpidem (Ambien), 2.3%
• Initiating toilet training too early can create
stress for the child and ultimately prolong the Hallucinogens
toilet training process • D-lysergic acid diethylamide (LSD): 0.9%
• 3,4-methylenedioxy-methamphetamine
Effective approaches in toilet training (MDMA) or ecstasy: 0.4%
• Training is started when the child is interested,
ready physically, and willing to cooperate Prescription medications
• Nonpunitive, reward-based techniques are • Misuse of prescription pain relievers (e.g.,
more effective oxycodone, hydrocodone); estimated preva-
• Recognition and affection are the best rewards lence rate of 4.7%; ages 18–25 years preva-
• Training takes time, and occasional relapses lence rate 8.5%
are normal
• Use of correctly sized potty for the child Steroids (anabolic)
• Watching and learning from parents, motiva- • Estimated prevalence rate of 0.6%
tion with cartoon underwear, allow for naked
Treatment of substance abuse disorder
time so the child can readily access the potty
• Referral to adolescent medicine or mental
health specialists may be appropriate for sub-
sequent evaluation, counseling, and possible
SUBSTANCE ABUSE pharmacotherapy
DISORDERS (SEE CHAP. 3 • Referral to a detoxification center:
“ADOLESCENT MEDICINE”) –– Treatment initially consists of managing
the varied symptoms of withdrawal, which
can range from a longing to reuse to hallu-
Cannabis use cinations and seizures
• The most common presentation among • Multimodal treatment to modify social fac-
adolescents tors in the family and at school that contribute
• 15% for cannabis use disorder1 to substance misuse behaviors
• Up to 45% for experimenting with cannabis • Specific therapeutic intervention:
Motivational interviewing
Stimulant abuse
• Stimulants include use of cocaine and meth-
amphetamine and misuse of prescription
stimulants, e.g., ADHD medications
PEARLS AND PITFALLS
• Cocaine: 0.8%, more in males • Maintain empathetic, relaxed and nonjudg-
• Methamphetamine: 1.2% mental attitude when inquiring about men-
• Prescription stimulants: 2% tal health is critical during patient
encounter.
Numbers reflect prevalence rates for the past year in the US in 2015
1
• Avoid undertreating mental health conditions,
among those aged 12 years or older, unless other age group is
specified.
risking an “act of omission.”
194 M. H. Ataalla
• Interview the adolescent individually, which school anti-bullying policies, and by parental
helps to establish confidentiality and trust. training.
• Asking adolescent about depression and sui- • Cognitive behavioral therapy/behavior man-
cidal thoughts does not trigger the problem; agement training is the first-line treatment for
depressed children may not express sadness crimes committed by minors (juvenile delin-
or a depressed mood to their parents. quency). Wilderness camps, boot camps, and
• Screen all adolescents from the age of juvenile awareness programs are ineffective.
12 years and yearly after that about mood • Exposure of children to 2 or multiple lan-
changes, irritability, dropping grades, social guages at home is not a reason for language
withdrawal, sadness, poor self-esteem, and delay.
difficulty concentrating. • Language delay, struggle in school, and learn-
• Cognitive behavioral therapy (CBT) is an ing problems can be the earliest signs of intel-
effective treatment for depression by altering lectual disabilities.
bad and negative thoughts into positive • Psychoeducational tests (IQ and achievement
thoughts and a better outcome. tests) are used for evaluation of intellectual
• Combination of CBT and medication is the disability; IQ test scores greater than 2 SD
best treatment for adolescent moderate to below the mean (< 70) in both cognitive and
severe depression and more effective than adaptive measures are suggestive of intellec-
using either therapy alone. tual disability.
• Do not forget to always educate on possible • Down syndrome (trisomy 21) is the most
side effects of medications. common genetic cause of intellectual disabil-
• The course of symptoms may change/evolve ity in general.
across different developmental stages. • Fragile X is the second most common genetic
• Provide close follow-up visits when indicated cause of intellectual disability after Down
and refer promptly as needed. syndrome.
• Promote resilience/hope and appreciate the • Screen for autism at the age of 18 months and
strength of the child and family, not only their 24 months or at any time if there is concern
weaknesses. about autism spectrum disorder (ASD).
• Masturbation is frequent in young children • Refer to early childhood intervention chil-
but is usually stopped when children are older dren less than 3 years with suspected ASD.
and aware of social norms. Behavioral modi- • Refer to local school district children 3 years
fication, distraction, and redirection are the and older with suspected ASD.
best strategies to limit masturbation • Speech therapy, occupational therapy, and
behavior. applied behavioral analysis are the best treat-
• Most children will outgrow thumb-sucking ment for children with autism.
and finger sucking without intervention. • No genetic studies or specific laboratories are
• Positive reinforcement, aversive techniques, indicated for children with ASD except if
competitive responses, and orthodontic there are dysmorphic features, family history
devices may be helpful in altering the habit of of intellectual disabilities, or possible under-
thumb-sucking if it persists beyond 4 years of lying condition.
age and complications are present. • Recommended workup for ASD with intel-
• Bullying usually when teachers are not lectual disability or global developmental
around; school and families must collaborate delay includes a DNA analysis for fragile X
to prevent this problem by having students syndrome and a chromosome microarray
supervised during breaks, by implementing analysis.
• Behavioral intervention alone is not effective Suggested Reading

in the treatment of attention-deficit/hyperac-
tivity disorder (ADHD). American Psychiatric Association. DSM-5 task
• Stimulants are the first-line and most effec- force. Diagnostic and statistical manual of men-
tive treatment in classic cases of ADHD. tal disorders: DSM-5. Washington, DC: The
American Psychiatric Association; 2013.
Chang WW. Pediatric sedation. Updated 8 May
References 2018. Medscape. n.d.. https://emedicine.
medscape.com/article/804045-overview#a8.
1. Karande S, Kulkarni M. Poor school perfor- Accessed 15 Oct 2018.
mance. Indian J Pediatr. 2005;72(11):961–7. Kliegman RM, Stanton B, St Geme J, Schor N,
Review. Behrman RE. Nelson textbook of pediatrics.
2. Floet AM, Scheiner C, Grossman L. Attention- 19th ed. Philadelphia: Saunders Elsevier; 2011.
deficit/hyperactivity disorder. Pediatr Rev. Martin A, Volkmar FR, Lewis M. Lewis’s child and
2010;31(2):56–69. adolescent psychiatry: a comprehensive text-
3. Glew G, Rivara F, Feudtner C. Bullying: children book. 4th ed. Philadelphia: Lippincott; 2007.
hurting children. Pediatr Rev. 2000;21(6):183– Rutter M, Bishop D, Pine D, Scott S, Stevenson
9; quiz 190. Review. JS, Taylor EA, Thapar A. Rutter’s child and
adolescent psychiatry. 5th ed. Hoboken: Wiley-
Blackwell; 2010.
Emergency Medicine
7
Jo-Ann O. Nesiama, Jennifer McConnell, and Kenneth Yen
RESPIRATORY DISTRESS –– May obstruct posterior pharynx when

supine
Definitions • Obligate nose breathers (particularly
• Respiratory distress < 4 months)
–– Interruption of the respiratory tract or the –– Nasal suctioning can significantly relieve
systems that control respiration respiratory distress due to nasal congestion
–– One of the most common pediatric com- • Omega-shaped and floppy epiglottis
plaints in the emergency room –– Structures easily collapse, and are not as
• Respiratory failure rigid as adult airway structures
–– Inability of the respiratory system to meet • Anterior airway with higher glottic opening
metabolic demand for oxygenation or at C2–C3 (versus C4–C5 in adults)
ventilation –– More difficult to visualize larynx during
–– Prominent cause of pediatric deaths, par- intubation
ticularly in infants • Significant anatomic variation with age
–– Respiratory failure is a primary cause of –– Shorter trachea
pediatric cardiac arrest ◦◦ Technically difficult intubation
◦◦ Easy to insert endotracheal tube too far
(right mainstem intubation)
Special Considerations ◦◦ Easy to lose artificial airway (dislodged
in the Anatomy of the Pediatric tube, esophageal intubation)
Airway • Smaller tracheal diameter:
–– Small increase in tracheal thickness causes
• Large occiput disproportionately larger obstruction
–– Causes flexion of airway when supine ◦◦ Poiseuille’s law: Resistance varies
• Large tongue inversely with fourth power of the radius
▪▪ Example: 1 mm thickening of trachea
decreases tracheal diameter by 20%
in an adult and 80% in a small child
• Narrowest portion of airway at cricoid ring
(versus at vocal cords in adults)
–– Uncuffed endotracheal tubes may provide
J.-A. O. Nesiama ∙ J. McConnell ∙ K. Yen (*)
adequate seal at “natural” cuff
Division of Pediatric Emergency Medicine, Department of
e-mail: Ken.yen@utsouthwestern.edu

198 J.-A. O. Nesiama et al.
• Small cricothyroid membrane Common causes of respiratory distress by ana-

–– Needle cricothyrotomy difficult tomical location
–– Surgical cricothyrotomy impossible in • Many causes of respiratory distress in pediat-
small children ric patients are commonly encountered and
have well-defined clinical syndromes
Localizing physical findings
• A careful physical can help rapidly localize Upper airway
the etiology of distress (Table 7.1) • Upper airway obstruction
Table 7.1 Physical exam findings seen in pediatric patients in respiratory distress
Physical
finding Description Physiology Important notes
Retractions Accessory muscle usage Counteract high negative intrathoracic Generalized finding of respiratory
(supraclavicular, pressure via increased respiratory effort distress
intercostal, abdominal)
Head Flexion–extension Emerges due to severe accessory muscle Indicative of severe respiratory
bobbing movement of head and use, seen particularly in small children and distress, potential impending
neck during inspiration infants respiratory failure
and expiration
Flaring Widening of the lateral Increases the upper airway diameter as an Often a late finding of respiratory
nares attempt to help relieve obstruction distress seen in small children and
infants
Stertor Low pitched, loud, Upper airway obstruction: may be due to Can improve with repositioning
rumbling, snoring sound large tongue, tonsils, or adenoids; poor (“sniffing position”) or jaw thrust
muscle tone; or altered mental status
“Hot Muffled, soft voice Obstruction of upper airway, typically May be seen in retropharyngeal
potato” oropharynx or pharynx abscess or peritonsillar abscess
voice
Hoarseness Rough or harsh Obstruction or abnormality of vocal cords Can indicate benign/minor
characteristic to voice or larynx pathology such as viral URI or
concerning pathology such as
injury to vagus or recurrent
laryngeal nerve
Barky Loud, “seal-” or “dog- Pathology or obstruction of subglottic area Commonly seen in acute viral
cough like” hacking cough croup
Stridor Harsh multiphonic, Obstruction of upper airway results in Can indicate acute viral croup, or
high-pitched upper turbulence and subsequent noise; other concerning pathology such
airway noise, “noisy inspiratory stridor most commonly glottic/ as aspirated foreign body or
breathing” subglottic in origin, expiratory stridor more epiglottitis
likely lower airway, e.g., carina
Grunting Soft, quick “puffing” Expiration against partly closed glottis, Often late finding of respiratory
expiratory noise attempt to maintain lung volume and distress, seen in small children and
prevent atelectasis via “auto-PEEP” infants
Wheezing Musical, continuous Expiratory wheezing indicates bronchi and Expiratory wheezing commonly
noise bronchiolar obstruction heard in asthma and bronchiolitis
Rales (fine Inspiratory, high-pitched, Opening of collapsed alveoli filled with Typically will not clear with
crackles) “Velcro-like” sounds secretions, indicate pathology at lung tissue repositioning and coughing
level
Rhonchi Inspiratory, mid- to Turbulence and secretions from secretions More likely to clear with
(coarse low-pitched “popping” or inflammation within bronchi and repositioning and coughing
crackles) sounds bronchioles
URI upper respiratory infection
7 Emergency Medicine 199
–– Anaphylaxis (hives, angioedema, atopy, Extrapulmonary

history of exposure to antigen, stridor, • Mediastinal masses (orthopnea, B symptoms,
hoarseness) hoarseness, hemoptysis, lymphadenopathy)
–– Nasal congestion/obstruction (congestion, • Pericardial tamponade (history of trauma,
rhinorrhea, concurrent upper respiratory orthopnea, hypotension, jugular vein disten-
infection [URI]) tion, pulsus paradoxus, muffled heart sounds)
–– Foreign body (history of coughing or chok- • Pleural effusion (risk factors such as pneumo-
ing event, stridor, drooling) nia/chemotherapy/autoimmune disorders,
–– Congenital/developmental airway anoma- orthopnea, pleuritic pain)
lies (choanal atresia, adenotonsillar hyper- • Pneumothorax/tension pneumothorax (possi-
trophy, laryngotracheomalacia, subglottic ble history of trauma or spontaneous sudden
stenosis/web/hemangioma, branchial cleft onset, unilateral absent breath sounds, possi-
abnormalities) ble hypotension, deviated trachea with medi-
• Upper airway infection astinal shift if tension is present)
–– Croup (URI symptoms, barky cough, fever,
inspiratory stridor) An approach to the differential diagnosis by
–– Epiglottitis (toxic appearance, fever, dys- clinical syndrome
phagia, drooling, inspiratory stridor) Respiratory distress with signs of upper airway
–– Peritonsillar abscess (fever, sore throat, obstruction (stridor, stertor, vocal change, dyspha-
trismus, dysphagia, drooling, vocal gia, drooling):
changes, uvular displacement) • If acute onset with fever, consider infection
–– Retropharyngeal abscess (fever, dyspha- –– Croup, peritonsillar abscess, retropharyn-
gia, drooling, vocal changes, neck stiff- geal abscess, tracheitis, epiglottitis
ness/pain with extension, torticollis) • If acute onset without fever, consider
–– Tracheitis (toxic appearance, fever, stri- –– Anaphylaxis, foreign body
dor—similar appearance to epiglottitis, • If chronic, consider
usually will have risk factors) –– Masses, congenital/developmental abnor-
malities such as tonsillar hypertrophy,
Lower airway vocal cord dysfunction, laryngotracheoma-
• Lower airway obstruction lacia, psychogenic causes
–– Anaphylaxis (hives, angioedema, atopy,
history of exposure to antigen, wheezing) Respiratory distress with signs of lower airway
–– Asthma/reactive airway disease (atopy, pathology (wheezes, rales):
history of bronchodilator use, expiratory • If acute onset with presence of fever, consider
wheezing, prolonged inspiratory to expira- infection/inflammation
tory ratio) –– Bronchiolitis, pneumonia, subacute for-
–– Bronchiolitis (previously healthy, no prior eign body, myocarditis
wheezing, concurrent URI symptoms) • If acute onset without fever, consider
–– Foreign body –– Asthma, bronchiolitis, viral/atypical pneu-
–– Tracheobronchomalacia (recurrent stridor monia, foreign body aspiration, anaphylaxis
or noisy breathing, acute or chronic exac-
erbations with concurrent URI) Respiratory distress with no signs of airway
• Lower airway infection obstruction, with the presence of tachypnea:
–– Pneumonia (cough, tachypnea, fever) • If acute onset tachypnea with fever, broaden the
differential to include a more systemic illness
–– Pneumonia, subacute foreign body, pulmo- Table 7.2 Initial simple airway maneuvers for patients in
nary embolism, myocarditis, pericarditis, acute respiratory distress
sepsis Airway
• If acute-onset tachypnea without fever and maneuvers Description
with concern for cardiac abnormality Airway Suctioning oro-/nasopharynx to remove
clearing secretions or debris
(arrhythmia, rubs, gallops, new murmurs, Nasopharyngeal airway
hepatomegaly, poor perfusion), consider Oral airway in patient with altered mental
–– Congenital heart disease, myocarditis, status
pericarditis, pericardial effusion/tampon- Airway Allow an awake child to assume position of
positioning comfort (e.g., tripoding)
ade, congestive heart failure, pleural
Head tilt and chin lift (“sniffing” position)
effusion to compensate for large occiput
• If acute-onset tachypnea without fever and no Jaw thrust/chin lift to open airway and
concern for cardiac abnormality: bring tongue forward
–– Very large differential diagnosis, obtain Shoulder roll to prevent forward flexion of
cranium due to large occiput
thorough history and physical
◦◦ Respiratory disorder (pneumonia, atel-
ectasis, pulmonary embolism, pulmo- –– Patient is able to vocalize clearly (speaking
nary deformity or mass) or loud crying)
◦◦ Metabolic (acidosis, hyperammonemia, • Airway is maintainable: Airway is obstructed
hyperglycemia, hepatic/renal disease) but maintained with simple measures
◦◦ Toxic (ingestions, methemoglobinemia) (Table 7.2)
◦◦ CNS disorder (seizure, mass, encepha- –– Patient able to vocalize, but abnormally
lopathy, neuromuscular disease, anxiety, (stertor, stridor, choking, coughing, dys-
pain) phonia, etc.)
◦◦ Intra-abdominal pathology (abdominal • Airway is not maintainable: Airway is
pain, distention, mass) obstructed and requires advanced interven-
◦◦ Hematologic (anemia, methemoglo- tion such as intubation
binemia) –– Unable to speak or absence of cry (gur-
gling, gasping, cyanosis, loss of conscious-
ness, extreme agitation, etc.)
I nitial Emergency Care for Patient
Breathing management
in Acute Respiratory Distress • Pediatric patients are less tolerant of hypox-
emia and hypercarbia
Airway management
–– Higher metabolic rate means more meta-
• Leading cause of pediatric cardiac arrest is
bolic demand
from respiratory failure
• Timely management of the pediatric airway Support oxygenation and ventilation
is key to resuscitation of pediatric patients • Provide supplemental oxygen for hypoxemia
with acute respiratory distress • Provide ventilatory support for hypercarbia
or inadequate/absent respiratory effort
Categorize the airway
• Make timely interventions for patient in acute
• Airway is clear: Airway is open and non-
respiratory distress (Table 7.3) (see Chap. 8
obstructed for normal breathing
“Critical Care” for additional details)
Table 7.3 Initial interventions in resuscitation of patients in cies. Abdominal emergencies in the setting of
acute respiratory distress pediatric abdominal trauma will be covered in the
Intervention Common uses Trauma and Burns section.
Nasal cannula Hypoxemia alone, will dry nasal
mucosa over time
Simple face mask Hypoxemia alone, significant room
air entrainment and mixing
The Pediatric Acute Abdomen
Non-rebreather Hypoxemia alone, allows for greater
face mask FIO2 via a reservoir • Abdominal complaints in pediatric patients
Heated high flow Hypoxemia and increased respiratory are common and often benign
nasal cannula effort, allows humidification and • Surgical abdominal emergencies must not be
heating, higher oxygen flow rates missed, due to high morbidity and mortality,
Noninvasive Hypoxemia and hypercarbia in select
positive pressure patients with respiratory failure but and require prompt recognition and timely
ventilation adequate airway protection and surgical evaluation
mentation; allows for positive
pressure delivery via sealed mask Findings that may indicate a surgical abdomen
Bag–valve–mask Hypoxemia and hypercarbia,
ventilation
• Bilious emesis
insufficient/absent respiratory effort,
a temporizing but life-saving measure –– Bilious emesis in infants is a surgical
while definitive airway/ventilatory emergency
support is being planned • Guarding
Inhaled States of reversible bronchospasm –– Active guarding
bronchodilators: (i.e., asthma exacerbation)
albuterol and
–– Passive guarding/rigidity
ipratropium • Distention
Nebulized racemic Suspected upper airway obstruction • Bowel sounds
epinephrine and edema with stridor (i.e., acute –– Absent bowel sounds may indicate ileus
infectious croup) • Tenderness
Intramuscular Suspected anaphylaxis
epinephrine –– Rebound tenderness is indicative of
peritonitis
• Associated symptoms
Summary –– Fever can signify a systemic inflammatory
response
• Correction of respiratory distress ultimately –– Bloody diarrhea can signify bowel wall
needs identification of the underlying cause necrosis and malperfusion
• Any disorder that causes respiratory distress
has the potential to be life-threatening Age-dependent presentation
• Remember the unique characteristics of the The age of the presentation can significantly shape
pediatric airway the differential diagnosis
• Initial resuscitation of the patient in acute • Infant: Maintain higher suspicion for congen-
respiratory distress requires attention to air- ital anomalies
way, breathing, and circulation –– Intussusception, malrotation with midgut
volvulus, incarcerated hernias, Meckel
diverticulum, pyloric stenosis
THE ACUTE ABDOMEN • School-aged child: Infectious causes become
increasingly common
The following section will focus on the presenta- –– Acute appendicitis
tion of the pediatric acute abdomen in the setting • Adolescent:
of emergency care, with a particular emphasis on –– Acute appendicitis, ectopic pregnancy,
the identification of surgical abdominal emergen- ovarian torsion, testicular torsion
General Principles of Management ◦◦ CT of the abdomen/pelvis is the radia-

tion exposure equivalent of more than
• Definitive treatment must be targeted at the 100 plain radiographs of the chest
etiology of the acute abdomen ◦◦ CT of the abdomen/pelvis increases risk
• There are general treatment principles that of radiation- induced solid cancers in
can be applicable in most cases children
◦◦ Due to radiation exposure risks:
Initial resuscitation ▪▪ CT is not recommended in the routine
• Attend to the ABCs (airway, breathing, evaluation of abdominal pain
circulation) ▪▪ Ultrasound should be considered first
–– Be alert for signs of shock and poor perfusion in the evaluation of acute appendicitis
–– Restore intravascular volume as clinically in children
appropriate –– Magnetic resonance imaging (MRI) will
• Pain control typically not be obtained in the emergency
–– Use an appropriate regimen to treat esca- setting for the evaluation of abdominal
lating degrees of pain pain
–– If warranted, opioids can be safely used in Select surgical abdominal emergencies (Table 7.4)
pediatric patients
• Nil per os (NPO) status
–– Do not allow the patient to eat or drink onsurgical Causes for an Acute
N
• For active bilious emesis and abdominal dis- Abdomen
tention, consider decompression
–– Nasogastric tube • Due to the small size of pediatric patients and
• Early surgical consultation possibility for referred pain, many extraintes-
–– In the presence of suspicion for an acute tinal or nonsurgical diseases can present with
surgical abdomen, prompt and early surgi- an acute abdomen and acute abdominal pain
cal consultation is important and should • Abdominal
not be delayed –– Gastroenteritis, viral or bacterial
• Imaging options –– Constipation
–– Abdominal plain radiographs can be help- –– Mesenteric adenitis
ful in the evaluation of an acute abdominal –– Gastritis/peptic ulcer disease
obstruction, foreign body, bowel perfora- –– Pancreatitis
tion, or constipation –– Gallbladder disease
◦◦ Identification of free air –– Hepatitis
◦◦ Air-fluid levels indicating ileus • Head, eyes, ears, nose, and throat (HEENT)
◦◦ Dilated loops of bowel in obstruction –– Streptococcal pharyngitis
◦◦ Radiopaque ingested foreign body –– Infectious mononucleosis
◦◦ Evaluation of stool burden • Pulmonary
–– Ultrasonography is the preferred first line –– Pneumonia
in many cases • Cardiac
◦◦ Acute appendicitis, intussusception, ovar- –– Pericarditis, myocarditis
ian torsion, pyloric stenosis, cholecystitis, • Renal
pancreatitis, nephrolithiasis, pregnancy –– Spontaneous bacterial peritonitis (with peri-
–– Computed tomography (CT) imaging toneal dialysis)
Table 7.4 Selected surgical abdominal emergencies, clinical features, and management
Features Disease process Clinical pearls Clinical pitfalls Initial management
Periumbilical pain Acute Most common abdominal The anatomic location of Fluid resuscitation, pain
migrating to the appendicitis emergency in children, the appendix can vary, control, appendix
right lower with peak incidence causing nonclassical ultrasound, surgical
quadrant at between 9 and 12 years; sites of pain consultation
McBurney’s point many will have pain with
walking or jumping; may
also have anorexia,
vomiting, diarrhea, and
fever
Suspected acute Perforated More likely to occur if Although appendicitis in Fluid resuscitation, pain
appendicitis appendicitis appendicitis present for infants is rare, the young control, appendix
followed by > 72 h, will often present child is more likely to ultrasound, surgical
sudden relief of with increasing signs of present with perforation consultation
pain, then peritonitis and toxicity due to difficulty in the
development of abdominal exam early on
generalized
peritonitis
Extreme colicky Intussusception Typically, 3 months to Intussusception can Fluid resuscitation,
pain with periods 6 years old, invagination of present with emesis and
ileocolic ultrasound,
of normalcy, bowel at lead point, most altered mental status
barium or air contrast
currant jelly stools common is ileocolic alone enema, surgical
consultation if
unsuccessful, anticipatory
guidance as
intussusception can recur
Tense inguinal Incarcerated Common cause of May not have known May need inguinal
bulge, vomiting inguinal hernia intestinal obstruction in prior history of hernia; ultrasound or abdominal
infants and children, 60% incarceration can radiograph if unclear
occurring within the 1st progress to strangulation diagnosis; otherwise,
year of life and bowel necrosis attempt immediate manual
within 24 h reduction if no sign of
bowel necrosis, and early
surgical consultation
Infant, projectile Pyloric stenosis Hypertrophied pylorus in Does not present with Fluid resuscitation, careful
nonbilious emesis, infant 2–5 weeks old, acute abdomen, but due electrolyte management,
hungry after occurs in 1 in 250 births, to potential for profound pyloric ultrasound,
emesis more common in first-born electrolyte disturbance, surgical consultation
males, can cause prompt diagnosis is
hypokalemic, important; alkalosis can
hypochloremic metabolic be severe enough to
alkalosis cause apnea
Acute-onset Malrotation Most serious cause of Variable presentation, Resuscitation in case of
bilious emesis, with midgut intestinal obstruction; from asymptomatic to signs of shock, flat and
abdominal pain volvulus congenital malrotation with failure to thrive; upright radiographs of
abnormal fixation of bowel complete volvulus for abdomen, upper GI series,
predisposes it to volvulize > 1 h causes gut immediate surgical
and obstruct; usually necrosis; a midgut consultation
presents neonatally; volvulus can cause death
however, 25% present of entire small bowel and
> 1 year ascending colon
(continued)
Features Disease process Clinical pearls Clinical pitfalls Initial management
Bilious emesis, Surgical Any child with prior Presentation can occur Fluid resuscitation,
abdominal adhesions with abdominal surgery or abdominal radiographs
within days, or months to
distention, obstruction peritonitis can develop years after surgery with more than one view
significant adhesions; requires low (e.g., flat, upright, and
abdominal surgical threshold of suspicion decubitus), gastric
history decompression, early
surgical consultation
Abdominal Necrotizing Typically presents in Although most common Resuscitation if signs of
distention with enterocolitis premature infants or in premature infants, can shock, radiographs of
systemic signs of neonates within 10 days of occur in term infants abdomen, prompt surgical
illness (lethargy, birth, may have history of and neonatal subspecialty
apnea, temperature birth asphyxia or stress consultation
instability) in
neonate
• Genitourinary ANAPHYLAXIS
–– Testicular torsion
–– Ovarian torsion Definition
–– Ectopic pregnancy • Serious, systemic, rapid-onset allergic/hyper-
–– Pelvic inflammatory disease sensitivity reaction
–– Dysmenorrhea • Variable clinical presentation and severity
• Urinary • Immunoglobulin E (IgE)-mediated, type I
–– Cystitis, pyelonephritis hypersensitivity reaction to antigen
–– Nephro-/urolithiasis
• Endocrine/metabolic Pathophysiology
–– Diabetic ketoacidosis • Antigen exposure leads to systemic mast cell
• Autoimmune/inflammatory and basophil degranulation with large hista-
–– Inflammatory bowel disease mine and cytokine release
–– Henoch–Schönlein purpura –– Vasodilation
–– Smooth muscle spasm (can also cause cor-
onary artery vasospasm)
Summary –– Increased vascular permeability
–– End stage: Loss of intravascular volume
• The differential diagnosis of the acute abdo- and hypotension
men in pediatric patients is broad, ranging in • Common likely antigens
nature from benign to life-threatening –– Food allergies (most common in pediatrics)
• A careful history and physical are important ◦◦ Peanut
to identify surgical emergencies ◦◦ Tree nuts (cashews, pecans, walnuts, etc.)
• Infants present a particularly diagnostic chal- ◦◦ Milk
lenge due to difficulty of exam and nonspe- ◦◦ Wheat
cific nature of presentation ◦◦ Soy
• Maintain a low threshold for early surgical ◦◦ Seafood (crustaceans)
consultation ◦◦ Fruit
–– Other miscellaneous allergens • Delayed phase/recurrence: Occurs from

◦◦ Antibiotics (penicillins, cephalosporins, hours to days after exposure (up to 72 h)
sulfonamides)
◦◦ Insect stings (Hymenoptera, fire ants) Differential diagnosis
• Anaphylactoid reaction
Diagnosis –– Non-IgE-mediated anaphylaxis
• Primarily a clinical diagnosis –– Most commonly caused by aspirin, nonste-
• If the presentation is unclear, a serum tryptase roidal anti-inflammatory drugs (NSAIDS),
can help assist future subspecialty management or radiographic contrast
–– Clinically indistinguishable from anaphylaxis
Clinical criteria –– Treatment is identical to anaphylaxis
• Anaphylaxis is highly likely with any of the
three clinical syndromes, in the context of an Treatment
exposure to a likely antigen: • Always attend to the ABCs
1. Acute onset of illness with skin and/or
• Intramuscular epinephrine is the first-line
mucosal symptom, and with one of the fol- treatment of choice in anaphylaxis and must
lowing symptoms: be administered immediately
◦◦ Respiratory compromise (such as –– Dosage: 0.01 mg/kg intramuscular
wheezing or stridor) ◦◦ Maximum of 0.3 mg in prepubertal
◦◦ Hypotension or altered mental status child
(AMS)/syncope or ◦◦ Maximum of 0.5 mg in adolescent
2. Two or more symptoms of the following –– Timing: Immediate
occurring acutely after exposure to likely ◦◦ Repeat at 5- to 15-min intervals
antigen: ◦◦ Up to 19% of patients will need a second
◦◦ Skin/mucosa (90%) (urticaria, angio- intramuscular dose
edema, flushing) –– Location: Mid-lateral thigh (vastus
◦◦ Respiratory (50–70%) (rhinorrhea, oro- lateralis)
pharyngeal/laryngeal edema, hoarse- –– Autoinjector dosing options
ness, stridor, wheezing, shortness of ◦◦ Autoinjectors can come in 0.1 mg,
breath) 0.15 mg, and 0.3 mg forms:
◦◦ Gastrointestinal (40%) (nausea, abdomi- ▪▪ 0.1 mg (7.5–14 kg)
nal pain, diarrhea, vomiting) ▪▪ 0.15 mg (15–30 kg)
◦◦ Circulatory (30%) (hypotension, ▪▪ 0.3 mg (>30 kg)
tachycardia) –– Pharmacokinetics
◦◦ Neurologic (syncope, sense of impend- ◦◦ Alpha- and beta-adrenergic agonist
ing doom, seizures, AMS) or induces bronchodilation, vasoconstric-
3. Age-specific decrease in systolic blood
tion, and decreased vascular permeability
pressure (BP) > 30% from normal or ◦◦ Effectively treating upper airway edema,
hypotension hypotension, and shock in addition to
bronchodilator and positive cardiac ino-
Biphasic presentation tropic and chronotropic effects
• Immediate phase: Occurs within minutes to
hours after exposure
◦◦ Intramuscular epinephrine achieves ▪▪ Idiopathic anaphylaxis

peak concentration faster than subcuta- ▪▪ Generalized urticaria from insect
neous injection sting (higher risk of more severe
▪▪ Intramuscular epinephrine is far safer reaction)
than intravenous (IV) epinephrine ▪▪ Patient lives in a remote or rural area
▪▪ Serious adverse effects of appropri- –– Referral to an allergy/immunology specialist
ately dosed intramuscular epineph-
rine are rare
▪▪ Side effects mimic signs of endoge- TRAUMA AND BURNS
nous catecholamine release: Pallor,
anxiety, tachycardia, tremor General principles of pediatric trauma
• Adjuncts therapies: Do not prioritize admin- • Primary survey (identify and treat any life-
istration of adjuncts over epinephrine threatening problems)
–– Diphenhydramine (H1 blockers) –– A Airway maintenance
–– Ranitidine (H-2 blockers) –– B Breathing and ventilation
–– Albuterol or racemic epinephrine –– C Circulation with hemorrhage control
–– Glucocorticoids –– D Disability; neurologic status (Glasgow
Coma Scale [GCS], pupils)
Patient disposition –– E Exposure/environment (remove clothing
• Due to potential for rebound anaphylaxis and and keep normal body temperature)
rapid deterioration, careful consideration of • Secondary survey
patient risk factors must be made at time of –– Vital signs
disposition from emergency care –– Detailed head-to-toe examination
• Risk factors that may necessitate admission –– History of traumatic event
to the hospital for observation: –– AMPLE history: Allergies, medications,
–– First presentation past illnesses, last meal, events or envi-
–– Infants ronment related to injury
–– Concomitant asthma
–– Unknown antigen
Home care after anaphylaxis Pediatric Head Trauma
• Counseling and follow-up are key for safe
disposition home after anaphylaxis • Most pediatric head trauma is not serious and
–– Avoidance of identified allergen requires only observation
–– Discussion of signs and symptoms of • Identification of serious head trauma in
anaphylaxis pediatric patients requires careful physical
–– Epinephrine auto-injector instruction examination and understanding of warning
◦◦ Because anaphylaxis has highly variable signs
clinical presentation between patients
Red flags in pediatric head trauma
and between episodes, it is not possible
• Severe mechanisms of injury
to predict disease severity
–– Motor vehicle collision (MVC) with
◦◦ All patients with anaphylaxis should be
◦◦ Patient ejection
prescribed an epinephrine auto-injector
◦◦ Fatalities
◦◦ High-risk patients:
◦◦ Rollover
▪▪ Coexisting asthma
▪▪ Reaction to trace amounts of food
–– Motor vehicle vs. pedestrian crash (MPC) Evaluation and management

or cyclist injury in those without helmets • CT scan to evaluate for other fractures and
–– Height of fall bleeding
◦◦ Infants under 2 years with falls greater • If nondisplaced, then usually heals without
than 3 ft intervention
◦◦ Children 2 years and over with falls • At higher risk for meningitis, but the utility of
greater than 5 ft prophylactic antibiotics is unclear
–– High-impact or high-speed object striking
head
• Patients at higher risk Temporal Skull Fracture
–– Infants in general, but particularly if
< 3 months
• Bleeding from ear or hemotympanum
–– Known bleeding disorder or
• Facial paralysis
anticoagulated
• CSF otorrhea and rhinorrhea
–– Multisystem injuries
• Vestibular symptoms, vertigo
–– Suspected nonaccidental trauma
• Leads to conductive, sensorineural, or both
• Patient with findings that are higher risk
types of hearing loss
–– AMS or acute change in mental status
◦◦ Lethargy Evaluation and management
◦◦ Irritability • CT scan (evaluate for longitudinal or trans-
◦◦ Loss of consciousness verse type)
–– Persistent vomiting • MR angiography/venography (MRA/MRV),
–– Severe headache CT angiography/venography (CTA/CTV)
–– Bulging fontanelle • Usually bedrest and raise head of bed
–– Focal neurologic findings initially
–– Seizures • Surgery if CSF still leaking after 1 week
• Facial paralysis, hearing loss, and vertigo are
longer-term issues
resentation and Localizing Findings
P
of Serious Injury Subdural Hematoma
Basilar Skull Fracture • Bleeding between the inner layer of the dura
mater and the arachnoid mater
Clinical presentation –– Tearing of the bridging veins across the
• Raccoon eyes (periorbital ecchymosis, bruis- subdural space
ing around eyes) –– Result of acceleration/deceleration mecha-
• Battle sign (mastoid ecchymosis, bruising nism (MVC, shaken babies)
behind the ears) –– Associated with cerebral contusion
• Hemotympanum –– If acute, the most lethal injury, but can be
• Cerebrospinal fluid (CSF) otorrhea or chronic, developing over days to weeks
rhinorrhea
• At increased risk for meningitis
• 75% will have a temporal skull fracture
• Gradually increasing headache and
confusion
• Ataxia, slurred speech Clinical presentation

• Loss of consciousness or fluctuating level of • Severe headache of rapid onset
consciousness • Vomiting
Diagnosis and management • Loss of consciousness
• CT scan (concave, crescent-shaped • Fever
hematoma) • Seizures
• Treatment ranges from monitoring to a small Diagnosis and management
burr hole to drain the hematoma to an open • CT scan
craniotomy. Treatment depends on size and • Support until neurosurgery
speed of growth
Retinal Hemorrhage
Epidural Hematoma • In an infant, this can indicate possible nonac-
cidental trauma
• Bleeding between the dura mater and the
skull
–– Often occurs from a break in temporal
Considerations in the Use of Head
bone with bleeding from the middle men-
ingeal artery Computed Tomography (CT)
• Children are at greater risk of developing
malignancy as a result of radiation exposure
• Classically causes loss of consciousness
• Because pediatric head trauma is common
(LOC) after head injury, followed by brief
and often benign, the use of CT imaging
regaining of consciousness (lucid period),
should be applied judiciously and after care-
and then LOC again
ful consideration
• Headache, confusion, vomiting
• The age of the patient, presence of other inju-
• With progression of bleed, pupils ipsilateral
ries, suspicion for nonaccidental trauma, and
to injury become fixed and dilated (compres-
presence or absence of warning signs should
sion of CN III) and gaze is “down and out”
all help guide the application of screening
(unopposed action of CN IV and VI)
head CT (Table 7.5) [1]
• Seizures and weakness on contralateral side
due to compression of crossed pyramidal
pathways
• Final stage is tonsillar herniation and death anagement of Clinically Significant
M
Diagnosis and management Head Trauma
• CT scan (biconvex, lens-shaped hematoma)
• Emergency burr hole and/or craniotomy • Attention to the ABCs, with particularly focus
on
–– Protection and establishment of a secure
Subarachnoid Bleed
airway
• Bleeding between the arachnoid membrane ◦◦ Particularly if unresponsive or GCS less
and pia mater than 8
–– Result of head trauma or can occur –– Close hemodynamic monitoring and repeat
spontaneously (e.g., ruptured cerebral neurologic assessments
aneurysm) – – Avoidance of hypothermia or hyperthermia
Table 7.5 Prediction rules for identification of children at low risk for clinically important traumatic brain injury found on
computed tomography (CT) imaging of the head
Age is less than CT is not recommended if the Observation vs. CT CT recommended if any of
2 years old following criteria are met (risk recommended if any of the the following are present
of clinically important TBI is following are present (risk of (risk of clinically important
low) clinically important TBI is TBI is high)
slightly elevated)
GCS 15 and no altered mental Occipital, parietal, or temporal GCS less than 15 or altered
status hematoma mental status
No palpable skull fracture History of loss of consciousness Palpable skull fracture
Frontal hematoma only Severe mechanism of injury
No loss of consciousness Not acting normally per caretaker
Nonsevere mechanism of injury
Acting normally per caretaker
Age is equal to CT is not recommended if the Observation versus CT CT recommended if any of
or greater than following criteria are met (risk recommended if any of the the following are present
2 years old of clinically important TBI is following are present (risk of (risk of clinically important
low) clinically important TBI is TBI is high)
slightly elevated)
GCS 15 and no altered mental History of loss of consciousness GCS less than 15 or altered
status mental status
No signs of basilar skull fracture History of vomiting Signs of basilar skull fracture
No loss of consciousness Severe mechanism of injury
No vomiting Severe headache
Nonsevere mechanism of injury
No severe headache
Pediatric Emergency Care Applied Research Network validated clinical prediction rules; adapted from Kuppermann et al.
[1], with permission
TBI traumatic brain injury, GCS Glasgow coma scale
–– Monitoring for signs of hypovolemic or –– Immediate consultation to neurosurgery

neurogenic shock can be life-saving for serious intracranial
–– Support to maintain cerebral perfusion injuries
pressure (CPP)
◦◦ CPP = mean arterial pressure (MAP) –
intracranial pressure (ICP) (or central N eck/Cervical Spine Trauma
venous pressure [CVP])
• Watch for clinical signs of increasing ICP • Penetrating neck injuries generally all need
–– Unequal pupil dilation (pressure on cranial surgical evaluation
nerves) • Blunt neck injury may warrant further evalu-
–– Abnormal posturing ation for vessel injury and cervical spine
–– Cushing’s triad: Irregular, decreased respi- injury
rations (caused by impaired brainstem
function), bradycardia, and systolic hyper- C ervical Spine Injury
tension (widening pulse pressure) • Relatively uncommon
• Management of increasing ICP • MVC, sports, and falls are most common
–– Mild hyperventilation etiologies
–– Intravenous mannitol or hypertonic saline • Children have different injury patterns because
(3%) may be needed of increased physiologic motion due to:
–– Larger size of head compared to trunk, abdominal injuries, primarily due to

which creates a larger fulcrum increased risk of gastrointestinal (GI)
–– Horizontally oriented facet joints injuries
–– Elevated ligamentous laxity –– Handlebar mark (handlebar-shaped ecchy-
–– Weaker muscles mosis over abdominal wall) at increased
• Children < 8 years old 87% of spinal injuries risk of small bowel hematoma and others
are above C3
• Children > 8 years old more commonly have Diagnosis and management
lower cervical injury (adult injury pattern) • Complete blood count (CBC), lipase, aspar-
tate transaminase (AST)/alanine transami-
nase (ALT) coagulation studies, uric acid
(elevated AST/ALT combined with positive
• Always suspect if head injury or facial
physical exam has good sensitivity)
fractures
• Abdominal radiograph to evaluate for free air
• Full neurologic exam, but note that > 20%
• CT scan (without contrast, with IV contrast,
with injuries will have normal exam
with IV and oral contrast)
Diagnosis and management
• Focused assessment with sonography in
• Cervical spine neck radiograph
trauma (FAST) exam is of unproven utility in
• CT
pediatrics but combined either with physical
• MRI
exam or serial exams can have good sensitiv-
• Proper cervical spine immobilization initially
ity and specificity
for all
• Conservative management for most, laparos-
• Some may need longer-term immobilization
copy for some
(halo) or surgery
• Laparotomy for significant injuries
Abdominal Trauma
PEDIATRIC WOUNDS
• Children are smaller in size; organs are pro- AND LACERATIONS
portionally larger; less fatty tissue around
major organs; weaker musculature; more Laceration
compliant rib cage, all which increase risk of
solid organ injury • A laceration is a traumatic disruption to the
• Most are MVC, others are MPC, sports, falls, dermis layer of the skin.
and nonaccidental trauma • Common locations are the face (~60%) and
• Most common unrecognized fatal injury upper extremities (~25%)
• Most lacerations in pediatric patients are non-
Clinical manifestation life-
threatening but require appropriate
• Exams may be difficult due to age, verbal management
ability, and fear • Severe and life-threatening lacerations must
• Tachycardia can be the only sign (even with be evaluated and treated promptly
45% circulating blood volume) –– Hemostasis: Apply pressure or tourniquet
• Have high index of suspicion for abdominal as necessary
injuries –– Injury to deeper structures: Especially at
–– Seatbelt sign (ecchymosis of abdominal high-risk areas like the neck (carotid) arter-
wall) after MVC has increased risk of intra-
ies, jugular veins, trachea, and esophagus suture, monitoring for infection, and use of
must be considered sunscreen to decrease scar formation
• Consider the need for tetanus prophylaxis
Management and treatment –– Prophylactic antibiotics not recom-
• Repair may be more difficult in pediatrics due mended with simple, uncontaminated
to fear, anxiety, and lack of cooperativity lacerations
–– Anesthetic and anxiolytic options ◦◦ Lacerations due to bites will typically
◦◦ Topical anesthetic LET (4% lidocaine, require antibiotics
1:2000 epinephrine, 0.5% tetracaine) ◦◦ Lacerations to hands and fingers with
▪▪ Effective 20–30 min after application associated distal fingertip fracture
▪▪ Blanching of the site after application
most often indicates achievement of
effective anesthesia Specialized Scenarios
◦◦ Local anesthetic may be used to prepare
for placement of sutures • Lip lacerations
▪▪ Injectable lidocaine alone or with –– An injury crossing the vermilion border
epinephrine will likely require subspecialist repair
◦◦ Distraction and soothing techniques –– Failure to align the vermilion border can
▪▪ Child life experts, toys, movies, result in a poor cosmetic outcome and per-
music, etc. manent lip deformity
◦◦ Oral/intranasal pharmacologic options –– Young and uncooperative patients may
◦◦ Inhaled and IV pharmacologic options additionally require varying degrees of
for procedural sedation anxiolysis and possibly sedation to repair
• Wound preparation well
–– Wound irrigation is the standard of care • Nail bed lacerations
–– Evaluation for possible foreign bodies or –– Repair of nail bed lacerations can be par-
complications ticularly painful and anxiety-provoking
–– Suspicion for foreign body or associated and may require a higher level of care
bony fracture should prompt radiographs –– Approximately half of all nail bed injuries
of the affected site are associated with a fracture of the distal
–– Tissue adhesive phalanx and will likely require subspecial-
◦◦ With selection of appropriate type of ist repair
laceration, tissue adhesive has good cos- ◦◦ Low threshold for obtaining plain radio-
metic outcome with benefit of no need graphs of the digit to evaluate for associ-
for suture or suture removal ated fracture
• Suture and staples ◦◦ Nail bed laceration with associated dis-
–– Selection of suture material (absorbable tal phalanx fracture may be an open
versus nonabsorbable) will depend upon fracture
the location and depth of the injury ▪▪ Open fractures require antibiotic
–– As a general rule, sutures should be evenly therapy
spaced • Ear lacerations
• Wound aftercare –– Significant ear lacerations will likely
–– All patients should be given follow-up require subspecialty repair
instructions for local wound care, cleans- –– Lacerations of the ear have the potential to
ing, timing (if necessary) of removal of involve the avascular cartilaginous support
–– Timely repair of ear laceration and close • Human bites

follow-up are important to avoid –– Three general types of injuries can lead to
complications complications:
◦◦ Auricular hematoma: Disruption to car- ◦◦ Closed-fist injury
tilage and underlying perichondrium can ◦◦ Chomping injury to the finger
lead to a hematoma, which, if untreated, ◦◦ Puncture-type wounds about the head
can cause cosmetic deformity of the ear caused by clashing with a tooth
(“cauliflower ear”) –– Human bites are contaminated and require
• Timing of suture removal antibiotic therapy
–– Timely removal of sutures reduces likeli- ◦◦ Eikenella corrodens, Staphylococcus
hood of suture tracks; better cosmetic species, Streptococcus species
outcome ◦◦ Human bites can also transmit the fol-
–– Face: 3–5 days lowing organisms: Hepatitis B, hepatitis
–– Scalp: 5–7 days C, herpes simplex virus (HSV), and
–– Trunk: 5–7 days syphilis
–– Extremities: 7–10 days
General evaluation
• Time and location of event
Animal and Human Bites
• Type of animal and its status (i.e., health,
• Dog bites rabies vaccination history, behavior)
–– Typically causes a crushing-type wound • Circumstances surrounding the bite (i.e., pro-
–– The extreme pressure of a dog bite may voked or defensive bite versus unprovoked
damage deeper structures such as bones, bite)
vessels, tendons, muscles, and nerves • Location of bites
–– Dog bites are contaminated and require
General management
antibiotic therapy
• Local public health authorities should be
◦◦ Staphylococcus species, Eikenella spe-
notified of all animal bites and may help with
cies, Pasteurella species
recommendations for rabies prophylaxis
• Cat bites
• Consider tetanus and rabies prophylaxis for
–– The sharp pointed teeth of cats usually
all wounds (Tables 7.6 and 7.7) [2, 3]
cause puncture wounds and lacerations
that may inoculate bacteria deep into the Table 7.6 Indications for tetanus vaccine and tetanus
tissues immune globulin in the United States
–– Infections caused by cat bites generally Contaminated
develop faster than those of dogs Clean and minor wounds (soil, dirt,
–– Cat bites are contaminated and require Vaccine status wounds feces, saliva)
antibiotic therapy Unknown or not Tetanus vaccine Tetanus vaccine
◦◦ Pasteurella species, Bacteroides up to date (< 3 only and tetanus immune
doses) globulin
species Series completed No tetanus No tetanus vaccine
• Other animals (> 3 doses) less vaccine or or immune globulin
–– Foxes, raccoons, skunks, and bats carry a than 5 years ago immune globulin
high risk for rabies Series completed If > 10 years If > 5 years since
–– Bat bites may be asymptomatic but > 5 years since final dose, final dose, tetanus
since final dose tetanus vaccine vaccine only
◦◦ If a bat is discovered within a patient’s only
sleeping quarters, rabies treatment Centers for Disease Control and Prevention [CDC] Advisory
should be given regardless of history of Committee on Immunization Practices on Tetanus 2018.
a known bite Adapted from Liang et al. [2]
Table 7.7 Indications for rabies prophylaxis and treatment in the United States
Vaccination status Intervention Description
No prior vaccine Human rabies vaccine Human rabies vaccine (human diploid cell vaccine) should
be administered IM on days 0, 3, 7, and 14
Human rabies immune Immune globulin (20 IU/kg) should be administered via
globulin (HRIG) direct infiltration around the wound, with any remaining
volume administered IM at an anatomical site distant from
the vaccine site (e.g., the opposite deltoid or lateral thigh)
Previously vaccinated Human rabies vaccine Human rabies vaccine (human diploid cell vaccine) should
be administered IM on days 0 and 3
Human rabies immune Not indicated
globulin (HRIG)
Centers for Disease Control and Prevention [CDC] Advisory Committee on Immunization Practices, 2010. Adapted from
Rupprecht et al. [3]
IM intramuscular
Laboratory • 100 ml of irrigation solution per centimeter of

• Fresh bite wounds without signs of infection wound
do not need to be cultured • Primary closure may be considered in limited
• Infected bite wounds should be cultured to bite wounds that can be cleansed effectively
guide antibiotic therapy (this excludes puncture wounds, i.e., cat bites)
• Other wounds are best treated by delayed pri-
Imaging studies mary closure
• Radiography is indicated if any concerns
exist that deep structures are at risk (e.g.,
hand wounds, deep punctures, crushing bites, Snake Bites
especially over joints)
• Most are nonpoisonous and are delivered by
Antibiotic therapy nonpoisonous species
• All human and animal bites should be treated • North America is home to 25 species of poi-
with antibiotics sonous snakes
• The choice between oral and parenteral anti- • Characteristics of most poisonous snakes:
microbial agents should be based on the –– Triangular head
severity of the wound and on the clinical sta- –– Elliptical eyes
tus of the victim –– Pit between the eyes and nose
• Oral amoxicillin–clavulanate is the initial –– Examples: Rattlesnakes, cottonmouth and
drug of choice for empiric oral therapy copperheads
• Amoxicillin alone does not provide adequate –– Few snakes with round head are venomous
coverage ◦◦ Example: Coral snakes (“red on yel-
• Parenteral ampicillin–sulbactam is the drug low—kill a fellow”)
of choice in severe cases
• Clindamycin in combination with trime- Clinical presentation
thoprim/sulfamethoxazole can be given if • Local manifestations
penicillin allergic –– Local swelling, pain, and paresthesias may
be present
Wound care
–– Soft pitting edema that generally develops
• Debridement and removal of devitalized
over 6–12 h but may start within 5 min
tissue
–– Bullae
• Irrigation is key to prevention of infection
–– Streaking
–– Erythema or discoloration –– Surgical assessment focuses on the injury

–– Contusions site and concern for the development of
• Signs of systemic toxicity compartment syndrome
–– Hypotension –– Fasciotomy is indicated only for those
–– Petechiae, epistaxis, hemoptysis patients with objective evidence of elevated
–– Paresthesias and dysesthesias—Indicate compartment pressure
neuromuscular blockade and should be
aware of possible respiratory distress (more
common with coral snakes) Black Widow Spider Bite
• The time elapsed since the bite is a necessary
component of the history • Black spider with bright-red or orange
–– Determine history of prior exposure to abdomen
antivenin or snakebite (this increases risk • Neurotoxin acts at the presynaptic membrane of
and severity of anaphylaxis) the neuromuscular junction; decreased reuptake
–– Assessment of vital signs, airway, breath- of acetylcholine and severe muscle cramping
ing, and circulation
Evaluation and management Clinical presentation
• Laboratory • Pricking sensation that fades almost
–– CBC with differential and peripheral blood immediately
smear • Uncomfortable sensation in the bitten extrem-
–– Coagulation profile, fibrinogen and split ity and regional lymph node tenderness
products • A “target” or “halo” lesion may appear at the
–– Blood chemistry, including electrolytes, bite site
blood urea nitrogen (BUN), creatinine • Proximal muscle cramping, including pain in
–– Urinalysis for myoglobinuria the back, chest, or abdomen, depending on
• Management the site of the bite
–– Support and transfer to definitive care • Dysautonomia that can include nausea, vom-
–– Bitten extremities should be marked proxi- iting, malaise, sweating, hypertension, tachy-
mal and distal to the bite, and the circum- cardia, and a vague feeling of dysphoria
ference at this location should be monitored Management
every 15 min for progressive edema and • Analgesics should be administered in doses
compartment syndrome sufficient to relieve all pain
–– Antivenom –– Oral or IV opioid analgesics
◦◦ Hemodynamic or respiratory instability –– Benzodiazepines are adjunctive for
◦◦ Abnormal coagulation studies cramping
◦◦ Neurotoxicity, e.g., paralysis of the • Hydration
diaphragm • Management of severe hypertension
◦◦ Evidence of local toxicity with progres-
sive soft tissue swelling
◦◦ Antivenom is relatively specific for the Brown Recluse Spider Bite
snake species against which they are
designed to protect • Dark, violin-shaped mark on the thorax
◦◦ There is no benefit to administer antive- • Venom causes significant local skin necrosis
nom to unrelated species due to risk of
anaphylaxis and expense Clinical presentation
• Typically, initially painless bite
• Rarely is the spider found or recovered • Antivenom therapy also may obviate or
• Erythema, itching, and swelling begin one to reduce the need for airway and ventilatory
several hours after the bite support
• Central ischemic pallor to a blue/gray irregu-
lar macule to the development of a vesicle
• The central area may necrose, forming an BURNS
eschar
• Induration of the surrounding tissue peaks at P ediatric Burn Classification
48–96 h
• Lymphadenopathy may be present • Superficial burn (formerly first degree)
• The entire lesion resolves slowly, often over –– Epidermal injury, intact dermis
weeks to months –– Erythematous, dry, and painful
Management –– Minor injuries that heal within 1 week
• Tetanus status should be assessed and updated without scarring
• Signs of cellulitis treated with an antibiotic • Partial thickness burn (formerly second
that is active against skin flora degree)
• Treatment is directed at the symptoms –– Partial injury of the dermis, often with
edema and blistering
–– Commonly are caused by scald injuries
Scorpion Stings and result from brief exposure to the heat
source
• The only scorpion species of medical impor- –– Blanchable pink or mottled red, often with
tance in the United States is the Arizona bark blisters and moist appearance
scorpion (Centruroides sculpturatus) –– Typically, painful
• Toxins in its venom interfere with activation –– Healed within 1–3 weeks with minimal
of sodium channels and enhance firing of scarring
axons • Deep partial thickness burn (formerly second
degree)
Clinical presentation –– Injury to epidermis and dermis
• Local pain is the most frequent symptom –– Dry, pale appearance, non-blanchable, may
• Small children may have more severe have speckled appearance
symptoms –– Less painful than partial thickness,
• Peripheral muscle fasciculation, tongue fas- although some sensation preserved
ciculation, facial twitching, and rapid discon- –– Heals after many weeks, often with sig-
jugate eye movements, which may be nificant scarring requiring surgical sub-
misdiagnosed as experiencing seizures specialty care for optimal cosmetic
• Agitation outcomes
• Extreme tachycardia • Full thickness burn (formerly third degree)
• Salivation –– Most serious and deepest type of burn
• Respiratory distress –– Destruction of epidermis and entire dermis
with necrosis
Management –– Pearly white, charred, hard, or parchment-
• Supportive care like appearance
–– Airway support and ventilation in severe –– Destruction of cutaneous nerves makes the
cases burn typically nonpainful
–– Analgesia and sedation
–– Loss of tissue elasticity makes the skin • Neurologic damage can develop in the years
scar-like and unable to expand following an electrical burn
◦◦ Circumferential or near-circumferential • Oral electrical burns affecting the commis-
burns can cause compartment syndrome, sure of the lips can be very scarring and at
vascular c ompromise of distal extremity, risk of bleeding from the labial artery
respiratory distress if present on the
chest
–– Burn cannot re-epithelialize and requires Description of Burn
surgical subspecialty care and often skin
grafting • The percent body surface area is an important
calculation in the classification of burns
• “Rule of Nines” can aid in calculation of per-
Inhalation Injury cent body surface area
–– Imagine the body as a flattened shape, with
• A large percentage of burn-related deaths are front and back surface areas added sepa-
due to associated smoke and inhalation rately (Fig. 7.1) [4]
injuries • Palmar method
• Evaluate all burn victims for potential for –– Surface of palm of hand can be used to
inhalational injury: approximate 1% body surface area in older
–– Signs of respiratory compromise: children
Coughing, stridor, wheezing, hoarseness –– Not useful in small children and infants
–– Signs of neurologic compromise:
Irritability or lethargy
–– Facial burns Management of Burns
–– Black (carbonaceous) sputum
–– Burned nasal hair and eyebrows Supportive home therapy for minor burns
• Early and aggressive airway management • Superficial burns (< 10% total body surface
prior to onset of airway obstruction area) can typically be treated on an outpatient
–– Suspected inhalation injury with signs of basis with supportive care, unless abuse is
airway compromise will need intubation suspected
and bronchoscopy –– Cotton gauze occlusive dressing to protect the
damaged skin from bacterial contamination:
◦◦ Eliminate air movement over the wound
Electrical Burns (thus reducing pain)
◦◦ Decrease water loss
• Electrical current can cause significant inter- ◦◦ Change dressings daily
nal damage via the arc of current through the –– Topical antimicrobial agent should be
body applied to the wound prior to the dressing
• External visible injury may be minimal for prophylaxis
• Depending upon the arc of the electrical cur- ◦◦ Silver sulfadiazine or bacitracin
rent, multiple complications can arise –– Application of various wound membrane
–– Cardiac arrhythmia (ventricular fibrilla- dressings can promote healing and lessen
tion) and myocardial damage pain of dressing changes
–– Rhabdomyolysis and renal failure –– Pain control
Fig. 7.1 Rule of nines: SURFACE OF PALM OVER 9 YEARS

Infants versus children
over 9 years old. (From FRONT BACK
Suguitan [4]), with
permission)
1% 4.5% 4.5%
4.5%
4.5%
4.5%
4.5%
INFANTS
18% 18%
FRONT BACK
1% 1%
9% 9%
4.5% 4.5% 4.5% 4.5%

18% 18%
9%
9%
9%
9%
7%
7%
7%
7%
◦◦ Alternating over-the-counter medications ◦◦ The first half of the fluid load is infused
◦◦ Opioid-containing medications for over the first 8 h post-burn
breakthrough pain ◦◦ The remainder is infused over the ensu-
▪▪ Caution in overreliance on opioids due ing 16 h
to risk for dependence, withdrawal, ◦◦ The infusion rates should be adjusted to
and opioid-induced hyperalgesia maintain a urine flow of 1 ml/kg per
hour
Initial treatment of extensive burns ◦◦ During the second 24 h, fluid adminis-
• Extensive burns (> 10% total body surface tration is reduced 25–50%
area) and burns to high-risk areas (face,
hands, neck, genitalia) will often require sub-
specialty care STATUS EPILEPTICUS
• Identification of airway involvement due to
risk for concomitant inhalation injury Definitions
–– Early and aggressive airway management • A seizure that lasts more than 30 min or
recommended • Multiple seizures that occur without return of
• Fluid resuscitation to prevent shock the individual to baseline, for a duration of
• Early excision and grafting of the burn wound not less than 30 min
coupled with early nutrition support
• Measures to treat sepsis Causes and risk factors
• Fluid administration • Many conditions can cause status epilepticus
–– Once the nature and extent of injury are –– Infection (viral, bacterial, fungal,
assessed, fluid resuscitation is begun parasitic)
–– Two large-bore IV catheters – – Trauma (intracranial hemorrhage, diffuse
–– Parkland formula for fluid requirements: axonal injury, cerebral contusion)
◦◦ 4 ml/kg/day for each percent of body – – Subtherapeutic anticonvulsant levels
surface area (BSA) burned (patients with known epilepsy)
–– Congenital abnormality ◦◦ In the first 5 min of seizure activity,

–– Metabolic (hypoglycemia, hyponatremia, before starting any medications, try to
hypocalcemia, hypomagnesemia, hyper- establish IV access and obtain samples
carbia, inborn errors of metabolism, pyri- for laboratory tests
doxine deficiency in neonates) ◦ ◦ Infuse isotonic IV fluids plus glucose. In
–– Vascular (hypoxic ischemic injury, cere- children younger than 6 years, use
brovascular accident, hypertensive intraosseous (IO) infusion if IV access
encephalopathy) cannot be established within 5–10 min
–– Toxicologic (tricyclic antidepressants, iso-
niazid, pesticides (organophosphates), Laboratory studies
heavy metals (lead), topical anesthetic • Finger-stick blood glucose
overdose) –– If serum glucose is low or cannot be mea-
–– Endocrine (hyper-/hypothyroidism, sured, give children 2 ml/kg of D25%
Addison’s disease) glucose
• Obtain basic metabolic panel, antiepileptic
Management drug levels, and other labs, depending on the
• Treatment should be based on an institutional history and physical examination
protocol • If the seizure fails to stop within 4–5 min,
prompt administration of anticonvulsants
General principles of management may be indicated
• Attend to the ABCs before starting any phar-
macologic intervention Potential anticonvulsant medication options
–– Airway • Anticonvulsant medication—selection can be
◦◦ Place patient in the lateral decubitus based on seizure duration as follows:
position to avoid aspiration of emesis –– Initial seizure activity (5–15 min):
and to prevent epiglottis closure over the ◦◦ Benzodiazepines are first-line GABA
glottis receptor blocker
◦◦ Make further adjustments of the head ▪▪ Preferred options: Lorazepam IV or
and neck if necessary to improve airway diazepam IV/rectal gel
patency ▪▪ Others: Midazolam IM or intranasal
◦◦ Suction secretions –– Prolonged seizures (> 15 min), if refrac-
◦◦ Immobilize the cervical spine if trauma tory to benzodiazepines:
is suspected ◦◦ Many options exist with no clear litera-
–– Breathing ture to support a particular therapy
◦◦ Administer 100% oxygen by face mask ◦◦ Selection should be made in consulta-
◦◦ Assist ventilation tion with a pediatric neurologist
◦◦ Use artificial airways (e.g., endotracheal ◦◦ Some options:
intubation) as needed ▪▪ Phenytoin or fosphenytoin IV
◦◦ Decompress the stomach as needed with ▪▪ Levetiracetam IV
a nasogastric tube ▪▪ Valproic acid IV
–– Circulation –– Continued seizure activity despite second-
◦◦ Carefully monitor vital signs, including and third-line agents
BP ◦◦ General anesthesia may be required
◦◦ Carefully monitor the temperature, as ◦◦ Options include inhalational agents,
hyperthermia may worsen brain pentobarbital anesthesia, continuous
damage benzodiazepines
▪▪ Anesthesia is titrated to achieve elec- • Altered level of consciousness or cognition—

troencephalogram (EE with burst sup- varying degrees of alteration of awareness
pression or flat line • Coma—the most severe form of altered level
◦◦ By this point, advanced airway must be of consciousness in which an individual is not
established, if not already aware of his or her surroundings and cannot
–– Other specific treatments may be indicated be easily aroused. A state lacking conscious-
if the clinical evaluation identifies precipi- ness (both wakefulness and awareness) that
tants of seizures cannot be overcome by stimulation
◦◦ Pyridoxine—IV/IM for possible depen- • Lethargy—state of altered level of conscious-
dence/deficiency or isoniazid toxicity ness that resembles deep sleep, from which a
▪▪ Pyridoxine-dependent seizures are a person can be aroused but immediately
rare but reversible cause of refractory returns to that state. Depressed consciousness
seizures in neonates: Consider admin- that, with adequate stimulation, can be
istration of pyridoxine for neonatal overcome
status epilepticus • Obtunded—state of altered level of con-
◦◦ Naloxone: IV preferably (if needed may sciousness in which a person has greatly
administer IM or subcutaneous) for nar- decreased responses and/ or is slow to respond
cotic overdose • Delirium (agitation)—abnormally activated
◦◦ Antibiotics: If meningitis is strongly consciousness with decreased awareness of
suspected, initiate treatment with antibi- environment from fluctuating global cerebral
otics prior to CSF analysis or CNS dysfunction, with inability or decreased abil-
imaging ity to focus, shift, or sustain attention
• Consciousness
Anticipatory guidance –– State of being awake and aware
• Patients with history of status epilepticus will –– Result of complex interplay of system
need: controls
–– Rescue abortive benzodiazepine (e.g., rec- ◦◦ Ascending reticular activating system
tal diazepam) for prolonged seizures for (ARAS) in brainstem and pons regulate
home administration prior to arrival of wakefulness
emergency medical services ◦◦ Connections from the ARAS project out
–– Seizure first aid teaching to the cortex and regulate awareness
• Consideration of additional benzodiazepine ◦◦ Function is dependent on many factors
to raise seizure threshold during times of ▪▪ Requires adequate perfusion; ade-
illness quate perfusion pressure; energy sub-
strate (oxygen, glucose, hydration);
electrolyte and acid-base balance
(glucose, carbon dioxide, blood pH);
LTERED MENTAL STATUS
A removal of toxins (waste products);
(AMS) body temperature; absence of neuro-
nal excitation/irritation (seizures)
Definitions
• AMS is a state of abnormally activated or Etiology of AMS
abnormally suppressed awareness/ • The differential diagnosis of AMS is extremely
consciousness broad and spans all possible organ systems
• It is a symptom and not a diagnosis—caused • Many possible causes of AMS have the poten-
by an underlying disease or by trauma tial to be life-threatening
–– Trauma Table 7.8 Glasgow coma scale [5, 6]

◦◦ Head trauma (subdural hematoma, epi- Score Infant Child Adult
dural hematoma, cerebral edema, severe Eye opening
concussions) 4 Spontaneous Spontaneous Spontaneous
3 Opens to speech Opens to Opens to
–– Infection speech sound
◦◦ Meningitis, encephalitis, sepsis, brain 2 Opens to pain Opens to Opens to
abscess, subdural empyema pressure pressure
◦◦ Sepsis with hypotension 1 None None None
–– Neoplasm Best verbal response
5 Coos and babbles Oriented, Oriented,
◦◦ Primary brain neoplasms or secondary appropriate appropriate
brain involvement, blockage of CSF 4 Irritable or cries Confused Confused
–– Vascular disease 3 Cries in response Words Words
◦◦ Cerebral hemorrhage vs. infarct (arterio- to pain
venous malformation, aneurysm, hem- 2 Moans in response Sounds Sounds
to pain
angioma, thrombotic stroke), 1 None None None
hypertensive emergency Best motor response
–– Obstruction to CSF 6 Moves Obeys Obeys
◦◦ Malfunctioning ventriculoperitoneal spontaneously and commands commands
purposefully
(CSF) shunt
5 Withdraws to Localizing Localizing
◦◦ Hydrocephalus touch
–– Metabolic anomalies 4 Withdraws to pain Normal Normal
◦◦ Hypoglycemia, hyponatremia, hypocal- flexion flexion
cemia, hypo-/hypermagnesemia, hypo- 3 Abnormal flexion Abnormal Abnormal
to pain flexion flexion
phosphatemia, metabolic acidosis and 2 Abnormal Extension Extension
metabolic alkalosis, Reye syndrome extension to pain
–– Toxic ingestions 1 None None None
◦◦ Many kinds of ingestions can cause
AMS (e.g., severe aspirin ingestion, car- ◦◦ Seizures: Postictal state, subclinical sta-
bon monoxide poisoning, salicylates, tus epilepticus
barbiturates, alcohol, antihistamines, ◦◦ Psychiatric disorders (pseudoseizure,
narcotics, phenothiazines, GHB [gamma conversion disorder)
hydroxybutyrate])
–– Advanced stages of medical illnesses Glasgow Coma Scale
◦◦ Liver failure, kidney failure, heart fail- • The Glasgow Coma Scale (GCS) score can
ure, respiratory failure be used to help convey the level of AMS
–– Specific disease states (Table 7.8) [5, 6]
◦◦ Dehydration –– GCS is 15 for individuals with normal level
◦◦ Hypoxemia or hypercarbia of mentation
◦◦ Hypothermia or hyperthermia – – GCS < 15 indicates an altered mental state
◦◦ Hemolytic uremic syndrome: CNS ◦◦ The subcategory including the lowest
infarction in basal ganglia number should be indicated, e.g., a GCS
◦◦ Intussusception: Infants can present ini- of 13 (−2 M) indicates −2 from the
tially with lethargy motor subcategory
Management ◦◦ Other ongoing resuscitation measures

• Treatment of AMS requires identification and may also be indicated
treatment of the underlying cause • Infection
• In all patients, attend to ABCs promptly –– In the presence of fever with meningismus,
–– Vital signs presume CNS infection
◦◦ Blood pressure –– Attend to airway, breathing, and circula-
▪▪ Attend to hypotension or severe tion promptly
hypertension –– Attempt diagnostic lumbar puncture if
▪▪ Fluid resuscitation patient is stable enough to tolerate it
◦◦ Heart rate –– Order broad-spectrum IV antibiotics or
▪▪ Attend to severe bradycardia or antifungal medications if suspected fungal
tachycardia process, and do not delay administration
◦◦ Hypothermia or hyperthermia ◦◦ Order additional broad-spectrum IV
▪▪ Thermoregulate patient antivirals for febrile neonate with risk
◦◦ Pulse oximetry factors for HSV encephalitis
▪▪ Administer supplemental oxygen –– If focal neurologic deficit or seizures are
▪▪ Assess risk for methemoglobinemia present, obtain noncontrast head CT prior
or carboxyhemoglobinemia to lumbar puncture
◦◦ Inadequate respiratory effort • Neoplasm
▪▪ Assist ventilation –– Space-occupying mass lesions in the brain
–– Point-of-care glucose can predispose to rapid decompensation
◦◦ Correction of hypoglycemia –– Attention to airway, breathing, circulation,
–– Point-of-care blood gas and neuroprotective maneuvers and
–– Consider empiric naloxone if clinical con- interventions
cern for opioid exposure –– Requires prompt consultation with appro-
Specific disease categories: priate subspecialties (neurosurgery,
• Trauma oncology)
–– This may be related to single system trauma • Metabolic abnormalities
(e.g., involving injury to the head/brain –– May be determined from results of testing
alone) or multisystem trauma or if adequate history is obtained, can help
–– Decreased GCS with head trauma is pre- aid diagnosis
sumed to be increased ICP until proven to –– Therapy is directed at the specific abnor-
be otherwise mal electrolyte abnormality
–– May not have a history of a traumatic event ◦◦ Examples: Administration of glucose in
if nonaccidental trauma is involved or the form of dextrose for hypoglycemia,
injury was unwitnessed or calcium for hypocalcemia
–– Initial steps • Toxic ingestions
◦◦ Attend to airway, breathing, and –– Attention to airway, breathing, circulation,
circulation and neuroprotective maneuvers and
◦◦ Maintain cervical-spine immobilization interventions
◦◦ Obtain emergent noncontrast head CT –– For specific antidotes, see Table 7.10
and prompt neurosurgical consultation • Suspected CSF shunt malfunction
◦◦ Neuroprotective measures: May need –– Attention to airway, breathing, circulation,
3% saline or mannitol, elevation of head and neuroprotective maneuvers
to 30°, midline positioning of head
–– Emergent head CT and radiographs to con- –– Absorbs substances and decreases

firm shunt continuity (“shunt series”) bioavailability
–– Timely neurosurgical consultation –– It is ineffective in the following (mnemonic
CHEMICaL)
◦◦ Caustics
POISONING AND TOXIC ◦◦ Hydrocarbons
EXPOSURE ◦◦ Ethanol (alcohols)
◦◦ Metals
Background ◦◦ Iron
• Children less than 6 years have the greatest ◦◦ Cyanide
risk ◦◦ Lithium
• Adolescent exposure either intentional or • Ipecac
occupational –– No longer recommended
–– Induction of emesis is particularly contra-
Prevention of poisoning indicated with ingestions of hydrocarbons
• Child-resistant packaging and caustics
• Anticipatory guidance in well childcare • Gastric lavage
–– Best provided at 6 months well child visit –– Contraindicated in hydrocarbons, alcohols,
prior to the onset of mobility and caustics
–– Poison-proofing child’s environment –– Not recommended in most ingestions
◦◦ Labeling all hazardous material –– May be considered with careful consider-
◦◦ Locking medicine cabinets and securing ation if life-threatening ingestion occurred
cleaning products within 30–60 min of seeking medical
◦◦ Securing all medications in purses and attention
handbags • Whole bowel irrigation
–– Reduces drug absorption by decontaminat-
Evaluation of a potentially toxic exposure ing the entire GI tract via large amounts of
• Call the poison control center, describe the an osmotically balanced polyethylene gly-
toxin, read the label, and follow the col-electrolyte solution (PEG-ES) to
instructions induce a liquid stool and empty the bowel
• Determine amount of exposure, number of –– Conclusive evidence that it improves out-
pills, number of the remaining pills, and/or comes is lacking
amount of liquid remaining –– May cause vomiting and abdominal disten-
• Determine time of exposure tion and lead to risk of aspiration
• Evaluate for progression of symptoms (any –– Should not be performed routinely, but
pattern of toxidromes) may be considered for
• Consider associated ingestions and underly- ◦◦ Potentially toxic ingestions of sustained-
ing medical conditions release or enteric-coated drugs
◦◦ Drugs not adsorbed by activated char-
General measures for toxic exposures
coal (e.g., lithium, potassium, and iron)
• For external exposures, remove clothes and
◦◦ Removal of illicit drugs in the body
wash the skin with soap and water
(e.g., “packers” or “stuffers”)
• For ingestions, can use activated charcoal if
within 60 min of ingestion
SPECIFIC INGESTIONS (TABLES • Any child with history of acute ingestion of

> 150 mg/kg of acetaminophen should be
7.9, 7.10, AND 7.11) [7, 8] referred for assessment and measurement of
acetaminophen level
Acetaminophen
• Responsible for one-third of all pediatric Clinical presentation (4 phases)
emergency department visits for ingestions • First 24 h
• The single toxic acute dose is generally con- –– Asymptomatic or nonspecific signs
sidered to be > 200 mg/kg in children, and –– Nausea, vomiting, dehydration, diaphore-
more than 7.5–10 g in adults and can cause sis, pallor
hepatic injury or liver failure –– Elevation of liver enzymes
Table 7.9 Toxidromes
Group Vital signs Mental status Pupils Other
Anticholinergics Increased P, T Delirium Mydriasis “Dry as a bone, red as a
beet” … a
Cholinergics Varies Normal to Varies “Drowning in secretions”
depressed DUMBBELLSa
Opioids Decrease BP, P, R, Depressed Miosis Hyporeflexia
T
Withdrawal from opioids Increase BP, P Normal to Mydriasis Vomiting, diarrhea,
anxious rhinorrhea
Sympathomimetics Increase BP, P, R, Agitated Mydriasis Tremor and seizures
T
Ethanol or sedatives/hypnotics Decrease BP, P, R, Depressed, Varies Hyporeflexia and ataxia
T agitated
Withdrawal from ethanol or Increase BP, P, R, Agitated, Mydriasis Tremor and seizures
sedatives/hypnotics T disoriented
Adapted from Hoffman et al. [5] with permission McGraw Hill Education
BP blood pressure, P Heart rate, R Respiratory rate, T temperature
a
See appropriate section
Table 7.10 Common antidotes for poisoning

Poison Antidote
Acetaminophen N-acetylcysteine (Mucomyst)
Anticholinergics Physostigmine
Benzodiazepines Flumazenil
β-blockers Glucagon; insulin/glucose
Calcium channel blockers Insulin and calcium salts
Carbon monoxide Oxygen
Cyanide Hydroxocobalamin (B12), Nitrites
Digitalis Digoxin-specific fragments antigen-binding (Fab) antibodies
Ethylene glycol and methanol Fomepizole
Iron Deferoxamine
Isoniazid (INH) Pyridoxine
Lead and other heavy metals, British anti-Lewisite (BAL) (dimercaprol)
e.g., mercury and arsenic
Methemoglobinemia Methylene blue
Opioids Naloxone
Organophosphates Atropine and pralidoxime
Salicylates Sodium bicarbonate
Sulfonylureas Octreotide
Tricyclic antidepressants Sodium bicarbonate
Table 7.11 Differential of toxic related findings (with mnemonic devices)

Finding Differential diagnosis
Anion gap metabolic acidosis C Carbon monoxide, cyanide
(Anion gap = Na – (HCO3 + Cl) A Aminoglycosides
T Theophylline, toluene (glue sniffing)
M Methanol, metformin
U Uremia
D Diabetic ketoacidosis, starvation
P Paraldehyde, paracetamol/acetaminophen,
propylene glycol
I Iron, isoniazid, ibuprofen, inborn errors of
metabolism
L Lactic acidosis
E Ethylene glycol
S Salicylates/aspirin
Widened QRS Bupivacaine, bupropion, carbamazepine, class I (quinidine, amiodarone,
procainamide) antiarrhythmics, class Ic (flecainide, propafenone, moricizine)
antiarrhythmics, cocaine, diphenhydramine, lamotrigine, tricyclic antidepressants
Prolonged QTc T Thiazides
O Ondansetron (antiemetics), opioids
(methadone)
Q Quinidine (class Ia), quinolones
(antibiotics)
R Risperidone (antipsychotics)
S Sotalol (class III)
A Antihistamines
D antiDepressants (TCA)
E Erythromycin and other macrolides
S SSRI (fluoxetine, sertraline)
Hypoglycemia H Hypoglycemic (sulfonylureas not
metformin)
O Others (quinine, quinolones, pentamidine)
BB β Blockers, Bactrim
I Insulin
E Ethanol
S Salicylates
Bradycardia and hypotension C Calcium channel blockers (diltiazem,
verapamil, amlodipine)
O Opiates
P Propranolol and other beta-blockers
(metoprolol, esmolol)
A Anticholinergics (organophosphates,
carbamates, neostigmine, sarin, VX)
C Clonidine and other central α-2 receptor
agonist (guanfacine, dexmedetomidine,
oxymetazoline)
E Ethanol
D Digoxin and cardiac glycosides (oleander,
foxglove, lily of the valley)
• 24 to 72 h post-ingestion
–– Tachycardia and hypotension 1000 Plasma Level of Acetaminophen µg per mL
–– Right upper quadrant pain with or without 500
hepatomegaly
–– Liver enzyme is more elevated 200
–– Elevated prothrombin time (PT) and biliru- 100 Pr

ob
ab
bin in severe cases le
He
50 pa
• 3 to 4 days post-ingestion tic
To
xic
–– Liver failure 10 No Hepatic Toxicity y
it
–– Encephalopathy, with or without renal
5
failure
–– Possible death from multiorgan failure or 0 4 8 12 16 20 24 Hours after lngestion
cerebral edema
Fig. 7.2 Rumack-Matthew nomogram for acetaminophen
• 4 to 14 days post-ingestion poisoning [6]
–– Complete recovery or death
Management Clinical presentation

• Measure serum acetaminophen level 4 h after • Nausea, vomiting, and epigastric pain
the reported time of ingestion • Drowsiness, lethargy, and ataxia may occur
• Acetaminophen level obtained < 4 h after • Anion gap metabolic acidosis, renal failure,
ingestion cannot be used to estimate potential seizure, and coma may occur in severe cases
toxicity (usually > 400 mg/kg)
• Check acetaminophen level 6–8 h if it is co- • May cause GI irritation, ulcers, decrease renal
ingested with other substance that slows GI blood flow, and platelet dysfunction
motility, e.g., diphenhydramine
Management
• Check liver function AST/ALT/coagulation
• Activated charcoal
parameters, renal function
• Supportive care
• Start N-acetylcysteine (NAC)
–– If acetaminophen level is above the treat-
ment line on Rumack-Matthew nomogram Salicylic Acid
(4 h and after) (Fig.7.2) [6]
–– If acetaminophen level is low or undetect- • Aspirin, certain antidiarrheal medications,
able with abnormal liver function topical agents, e.g., keratolytics and sports
–– Patients with a history of potentially toxic creams
ingestion more than 8 h after ingestion • Refer to an emergency department for inges-
(single dose > 200 mg/kg in children and tions > 150 mg/kg
more than 7.5–10 g in adults) • Ingestion of > 200 mg/kg is generally consid-
• Liver transplant for liver failure ered toxic; > 300 mg/kg is more significant
toxicity; > 500 mg/kg is potentially fatal
Ibuprofen
• Inhibit prostaglandin synthesis • Acute salicylism
–– Nausea, vomiting, diaphoresis, and tinnitus
• Moderate toxicity Beta-Blockers

–– Tachypnea, hyperpnea, tachycardia, and
AMS • Acebutolol, atenolol, bisoprolol, metoprolol,
• Severe toxicity nadolol, sotalol, and propranolol
–– Hyperthermia and coma
Management • Hypotension, bradycardia, atrioventricular
• Consider activated charcoal (AV) block, heart failure
• Check blood gas (respiratory alkalosis, meta- • Bronchospasm
bolic acidosis, and high anion gap) • Hypoglycemia, hyperkalemia
• Check serum level every 2 h until it is consis- • Stupor, coma, seizures
tently down trending
• IV fluids Management tailored to the symptoms
• Sodium bicarbonate therapy in the symptom- • Consider dose of activated charcoal
atic patients • Hypotension/bradycardia/AV block: Fluid
• Goal of therapy includes a urine pH of 7.5– boluses, beta-agonists, vasopressors, atro-
8.0, a serum pH of 7.5–7.55, and decreasing pine, possibly pacing
salicylate levels • Hypoglycemia: Glucose
• Hyperkalemia: Calcium gluconate, dextrose
and insulin, sodium bicarbonate, possibly
Anticholinergics dialysis
• Two special cases
• Diphenhydramine, atropine, scopolamine,
–– Propranolol → causes sodium channel
hyoscyamine, jimsonweed (Datura stramo-
blockade → QRS widening → treat with
nium), and deadly nightshade (Atropa
sodium bicarbonate
belladonna)
–– Sotalol → causes potassium efflux block-
Clinical presentation (anticholinergic symptoms) ade → prolonged QT → monitor for
• Dry as a bone: Dry mouth, decreased sweat- torsades
ing, and urination
• Red as a beet: Flushing
arbamazepine
C
• Blind as a bat: Mydriasis, blurred vision
• Mad as a hatter: Agitation, seizures, Clinical presentation
hallucinations • Mild ingestion:
• Hot as a hare: Hyperthermia –– CNS depression
• Bloated as a toad: Ileus, urinary retention –– Drowsiness
• Heart runs alone: Tachycardia –– Vomiting
–– Ataxia
Management
–– Slurred speech
• Consider activated charcoal
–– Nystagmus
• Supportive care
• Severe intoxication:
• Physostigmine can be considered for severe
–– Seizures
or persistent symptoms
–– Coma • Bradycardia
–– Respiratory depression • Hypotension
–– Can cause transient initial hypertension
Management • Apnea
• Supportive measures Management
• Charcoal hemoperfusion for severe • Supportive care, e.g., intubation, atropine,
intoxication dopamine as needed
• Charcoal usually not recommended due to
CNS depression
Cardiac Glycosides (Digitalis)
• Digoxin, foxglove plants, oleander, lily of the Opiates
valley (Convallaria)
• Morphine, heroin, methadone, propoxy-
Clinical presentation phene, codeine, meperidine
• Nausea and vomiting • Most cases are drug abuse
• CNS depression (confusion)
• Blurry vision
• Cardiac conduction abnormalities (irregular
• Common triad of opiate poisoning:
pulse, bradycardia or tachycardia)
–– Pinpoint pupil
Management
–– Mental depression (lethargy to coma)
• Electrocardiogram (ECG) and digoxin levels
–– Respiratory depression
• Hypotension with no change in heart rate
• Atropine, cardiac pacing (for severe
• Decreased GI motility, nausea, vomiting,
bradycardia)
abdominal pain
• Magnesium sulfate (for premature ventricular
Management
contractions [PVCs])
• Supportive care, e.g., airway, breathing, and
• Management of hyperkalemia, hypokalemia,
circulation; intubation; fluids as necessary
hypomagnesemia
• Naloxone as needed
• If severe, digoxin-specific antibody
–– Half-life of naloxone is short
fragments
–– Repeat doses and continuous infusions
may be necessary
–– Cautious use in known opioid-dependent
Clonidine
patients
• Antihypertensive medication with α-2 adren- ◦◦ Can induce withdrawal
ergic receptor blocking ability
• Commonly used in children with attention-
deficit hyperactivity disorder (ADHD) Phenothiazines
• Dose as small as 0.1 mg can cause toxicity in
• Promethazine, prochlorperazine, and
children
chlorpromazine
• Lethargy Clinical presentation
• Miosis • Hypertension
• Cogwheel rigidity Prevention of CO poisoning

• Dystonic reaction (spasm of the neck, tongue • CO detectors
thrusting, oculogyric crisis) • Maintenance of fuel-burning appliances
• CNS depression • Yearly inspection of furnaces, gas pipes, and
chimneys
Management • Car inspection for exhaust system
• Activated charcoal • No running engine in a closed garage
• Manage high BP • Avoid indoor use of charcoal and fire sources
• Diphenhydramine for dystonic reaction
• Headache, malaise, nausea, and vomiting are
Tricyclic Antidepressants (TCAs) the most common flu- or food poisoning-like
early symptoms
• TCAs can cause significant toxicity in chil- • Confusion, ataxia, syncope, tachycardia, and
dren even with ingestion of 1–2 pills (10– tachypnea at higher exposure
20 mg/kg) • Coma, seizure, myocardial ischemia, acido-
sis, cardiovascular collapse, and potentially
death in severe cases
• Anticholinergic toxidrome: Delirium, mydri-
asis, dry mucous membrane, tachycardia, Management
hyperthermia, hypotension, and urinary • Evaluate for COHb level in symptomatic
retention patients
• Cardiovascular and CNS symptoms dominate • Arterial blood gas with CO level
the clinical presentation • Check creatine kinase in severe cases
• Most common cardiac manifestations: • ECG in any patient with cardiac symptoms
Widening of QRS complex, PVCs, ventricu- • 100% oxygen to enhance elimination of CO,
lar arrhythmia use until CO < 10% and symptoms resolve
• Refractory hypotension is poor prognostic • Severely poisoned patient may benefit from
indicator and is the most common cause of hyperbaric oxygen especially if COHb
death in TCA toxicity > 25%, significant CNS symptoms, or cardiac
dysfunction
Management
• Supportive measures, ABCs
• ECG: Cyanide
–– A QRS duration > 100 ms identifies patients
at risk for seizures and cardiac arrhythmia • Seeds (cherries, apricots, peaches, apples,
–– An R wave in lead aVR of > 3 mm is an plums); cassava; burning plastics (nitrile-
independent predictor of toxicity containing products); nitroprusside; some
• Start sodium bicarbonate therapy: QRS dura- pesticides
tion > 100 ms, ventricular dysrhythmias, • Amygdalin is contained in seeds and produces
hypotension, and seizures hydrogen cyanide, which is a potent toxin
• Inhibition of cellular respiration (cytochrome
c oxidase) stops ATP production
Carbon Monoxide (CO)
• Wood-burning stove, old furnaces, and Clinical presentation
automobiles • Decreased level of consciousness
• Low exposures—weakness, headache, dizzi- • Ethanol can be used if fomepizole is

ness, confusion unavailable
• Severe exposures—seizure, apnea, cardiac arrest • Hemodialysis (consider if > 30 ml methanol
• Cherry red skin ingested)
Management
• Supportive measures Iron
• Hydroxocobalamin (vitamin B12), nitrites
• Ingestion of > 60 mg/kg/dose is toxic
thylene Glycol Ingestion

E
(Antifreeze)
• Gastrointestinal stage (30 min−6 h)
Clinical presentation –– Nausea, vomiting, and abdominal pain
• Nausea, vomiting, CNS depression, anion –– Hematemesis and bloody diarrhea in severe
gap metabolic acidosis cases
• Hypocalcemia, renal failure due to deposition • Stability stage (6–24 h)
of calcium oxalate crystals in the renal tubules –– No symptoms: Patient must be observed
during this stage
Management • Systemic toxicity within (48 h)
• Osmolar gap can be used to estimate ethylene –– Cardiovascular collapse
glycol level –– Severe metabolic acidosis
• IV fluids, glucose, and bicarbonate as needed • Hepatotoxicity and liver failure (2–3 days)
for electrolyte imbalances and dehydration • Gastrointestinal and pyloric scarring
• Fomepizole (2–6 weeks)
• Ethanol can be used if fomepizole is unavailable
Management
• Abdominal radiograph (may show pills and
Methanol need for GI decontamination)
• Serum iron < 300 mcg/dl is nontoxic
• Toxicity primarily caused by formic acid • Chelation with IV deferoxamine if serum iron
> 500 mcg/dl
• Drowsiness, nausea, and vomiting Mushrooms
• Metabolic acidosis
• Visual disturbances: blurred and cloudy • Ingestion of mushrooms can have fatal conse-
vision, feeling of being in a snowstorm, and quences in species that harbor amatoxins
untreated cases can lead to blindness (e.g., Amanita) and related compounds
Management Clinical presentation

• Osmolar gap (may be used as surrogate • Nausea, vomiting, and diarrhea; delayed
marker until methanol blood level is onset (6 h)
available) • A second latent period is followed by acute
• IV fluids, glucose and bicarbonate as needed and possibly fulminant hepatitis beginning
for electrolyte imbalances and dehydration 48–72 h after ingestion
• Fomepizole
Management • Benzene is known to cause cancer

• Activated charcoal • Inhalants, including toluene, propellants, and
• Whole bowel irrigation volatile nitrite, can cause dysrhythmias and
• Supportive care, including liver transplant, if sudden death
necessary, is the mainstay of therapy
• Cough, tachypnea, respiratory distress
Caustic Ingestion
Management
• Strong acid and alkalis < 2 or > 12 pH can • Emesis and lavage are contraindicated
produce severe injury even in small-volume • Activated charcoal should be avoided due to
ingestion risk of inducing vomiting
• Patient can have significant esophageal injury • Observation and supportive care
without visible oral burns
Clinical presentation rganophosphate and Carbamate

O
• Pain, drooling, vomiting, and abdominal pain Insecticides (Nerve Gas Agents)
• Difficulty in swallowing, or refusal to
swallow • Inhibit anticholinesterase
• Stridor and respiratory distress are common
presenting symptoms Clinical presentation
• Esophageal stricture caused by circumferen- • (DUMBBELLS) “Drowning in your own
tial burn; requires repeated dilation or surgi- secretions”
cal correction –– Diarrhea
–– Urination
Management –– Miosis
• Supportive measures, ABCs –– Bradycardia
–– Inducing emesis and lavage are –– Bronchospasm
contraindicated –– Emesis
–– Endoscopy should be performed within –– Lacrimation
12–24 h in symptomatic patients, or on –– Lethargy
basis of history and characteristics of –– Salivation and Seizures
ingested products
Management
• Wash all exposed skin with soap and water
Hydrocarbons and immediately remove all exposed
clothing
• Products contain hydrocarbon substances,
• Fluid and electrolyte replacement, intubation,
mineral spirits, kerosene, gasoline, turpen-
and ventilation if necessary
tine, and others
• Atropine and pralidoxime
• Aspiration of even small amount can be seri-
ous and potentially life-threatening
• Pneumonitis is the most important manifesta-
tion of hydrocarbon toxicity
OREIGN BODY ASPIRATION

F • Bilateral decubitus views may aid in diagno-
sis: Bilateral to compare which lung exhibits
AND INGESTION air trapping, which may be where the foreign
body is lodged
Foreign Body Aspiration
• The presence of normal chest radiographs
• Occurs in the context of child’s play/explora- does not exclude this diagnosis in the pres-
tion of environment ence of a compelling history
• Foreign bodies may lodge in the upper or • For patients in severe respiratory distress,
lower respiratory tract immediate bronchoscopy to remove the for-
eign body emergently is key to treatment
Upper airway
• The most commonly implicated foods are
oreign Body Ingestion
F
–– Candy, meat, hot dogs, grapes
• Associated symptoms include • Most children will have a history of ingested
–– Choking, coughing, stridor, respiratory foreign body, often reported by a caregiver or
distress playmate/sibling
–– May result in complete airway obstruction • Most commonly ingested foreign bodies are
• In patients with complete airway obstruction, –– Food (meat)
emergency procedures may be life-saving –– Followed by coins, pins, toy parts, button
–– Back blows in infants batteries, magnets
–– Heimlich maneuvers in older children • Most will pass harmlessly through the GI
–– If patient becomes unconscious, may need tract
to initiate cardiopulmonary resuscitation • Foreign bodies may lodge in areas where
(CPR) there is physiological/anatomic narrowing of
◦◦ Convert to rescue breaths and chest the lumen of the GI tract
compressions –– Lodging may occur secondary to patholog-
–– If all of the above are unsuccessful, then ical narrowing of the lumen of the GI tract
advanced airway techniques may be (e.g., from previous surgeries such as in
necessary tracheoesophageal fistula, esophageal/duo-
denal webs)
Lower airway
• Symptoms, if present, may include coughing,
• More common in younger children
choking, foreign body sensation, throat pain,
• Foreign body may lodge in the right or left lung
drooling, vomiting, refusal or inability to tol-
• Symptoms may involve coughing, choking,
erate fluids/food
wheezing, or may be asymptomatic
• Children may also be completely
• Diagnosis may be delayed due to lack of
asymptomatic
symptoms
Esophagus
Management
• The esophagus is the most common site for
• If the patient is stable and not in respiratory
ingested foreign bodies to become lodged
distress, neck and/or chest radiographs may
• Ingested foreign bodies typically become
help with diagnosis
lodged in one of three sites:
–– Not all inhaled foreign bodies are radi-
–– At the thoracic inlet
opaque and may not be visualized on radio-
graphs even if present
–– Mid-esophagus, at the level of the carina DIABETIC KETOACIDOSIS

and aortic arch
–– Esophago-gastric junction
(DKA)
Management KA in Pediatric Patients

D
• If the patient is asymptomatic and there is no
• DKA is a severe complication of type 1
airway compromise, may do neck and/or
diabetes
chest radiographs
• Occurs in 25–40% of new-onset type 1
• If foreign body is not visualized and patient is
diabetes
asymptomatic, then can do an esophagram
• Inadequate relative or absolute deficit of insu-
• If foreign body is lodged in the esophagus,
lin leads to starvation of insulin-dependent
may need removal by esophagoscopy
tissue (muscle, liver, fat) with resultant
• Some authorities report the use of glucagon
hyperglycemia
with varying degrees of success
• Starvation state triggers a cascade of hor-
• Emergent removal is indicated for two or
monal release such as glucagon, catechol-
more magnets, button batteries, lodged sharp
amines, cortisol, cytokines
objects
• Results in a catabolic state with lipolysis, pro-
Stomach and Lower Gastrointestinal Tract teolysis, adipose tissue metabolism into free
• Most foreign bodies in the stomach will pass fatty acids, hepatic conversion of fatty acid to
harmlessly through the remaining portion of keto-acids, and anion gap metabolic acidosis
the GI tract • Hyperglycemia causes osmotic diuresis with
• Single, not sharp foreign bodies may be man- hypovolemia and dehydration
aged conservatively and observed
• Parents may be advised to watch patient Diagnostic laboratory findings
stools, or have repeat abdominal radiographs • Acidosis (venous pH < 7.3, serum bicarbon-
within 1 week to assess if foreign body has ate < 15 mEq/L)
been eliminated • Serum glucose > 200 mg/dL
• If two or more button batteries or magnets are • Glucosuria, ketonemia, and ketonuria
located in any portion/part of the GI tract,
Degrees of severity of DKA
consultation with a gastroenterologist to
• Mild: pH > 7.2 and < 7.3, bicarbonate
facilitate removal is necessary
< 15 mEq/L
–– If not removed, the magnets may “adhere”
• Moderate: pH > 7.1 and < 7.2, bicarbonate
together across tissues/tissue planes and
< 10 mEq/L
cause necrosis with ensuing perforation
• Severe: pH < 7.1, bicarbonate < 5 mEq/L
• Sharp objects (particularly if longer than
5 cm) in the stomach and lower GI tract Review of pathophysiology
require consultation with a • Inadequate insulin secretion
gastroenterologist –– Decrease in cell uptake of glucose, leading
to hyperglycemia
–– Hyperglycemia causes osmotic diuresis,
leading to dehydration
–– Compounded by stress response with acti- Cerebral Edema

vation of gluconeogenesis, glycogenolysis,
and increased insulin resistance • Most serious immediate risk to child in DKA
• Protein catabolism with mortality rate of 40–90%
–– Adipose tissue broken down into fatty • Occurs in 1/100 pediatric cases during the
acids first 24 h of DKA
–– Fatty acids converted to keto-acids in the • Causes 50–60% of diabetes-related pediatric
liver deaths
• Dehydration • Pathophysiology of cerebral edema is
–– Osmotic diuresis from hyperglycemia controversial
–– Compounded by acidosis with nausea, • Risk factors for cerebral edema continue to
vomiting, and oral intolerance be studied
–– Typically occurs in setting of several weeks –– New-onset diabetes
of polyuria, polydipsia, and weight loss –– Age < 3 years
–– Dehydration can be profound and lead to –– High BUN at presentation
shock state –– Low PCO2
• Acidosis –– Treatment with bicarbonate
–– Keto-acids from protein catabolism cause –– Failure of serum sodium to correct with
anion gap acidosis therapy
–– Poor tissue perfusion in setting of severe
dehydration causes lactic acidosis Signs
• Electrolyte abnormalities • AMS, from agitation to frank coma
–– Potassium • Severe headache
• Acidosis causes extracellular shift of • Heart rate deceleration
potassium with hyperkalemia • Focal neurologic deficit
• Excess serum potassium is cleared by
kidney Treatment
• Hypovolemia stimulates secondary • Immediate recognition
hyperaldosteronism and further urinary • Immediate mannitol 1 g/kg over 10–20 min
potassium excretion • Cerebral edema is a reversible condition with
• Factors leads to total body potassium prompt treatment
depletion in all patients with DKA
Principles of initial resuscitation of DKA in the
• Measured serum potassium levels are
emergency department
highly variable at presentation (hypoka-
• Treatment of DKA is often based on institu-
lemia, normal, or hyperkalemia) and do
tional protocol
not correlate with degree of total body
• General concepts are
potassium losses
–– Initial rehydration with isotonic fluid
–– Phosphate
◦◦ 10–20 ml/kg of 0.9% normal saline over
• Acidosis stimulates phosphate depletion
1–2 h
due to renal phosphate excretion
◦◦ Goals: adequate tissue perfusion, not
–– Sodium
normovolemia
• Hyperglycemia and osmotic diuresis
–– Administration of insulin as continuous IV
lead to renal sodium losses and typically
infusion
hyponatremia
◦◦ Regular insulin 0.1 unit/kg/h via IV line
–– Addition of dextrose in fluid after serum –– Caution with replacement of phosphate is

glucose begins to fall advised due to risk of precipitating hypo-
◦◦ Varying concentrations of dextrose from calcemia, renal failure, and arrhythmias
5% up to 12.5% via IV line
◦◦ Plasma glucose target range 200– Ongoing management
300 mg/dL • Children with DKA typically require subspe-
–– Careful correction of electrolyte cialty monitoring
disturbances • Admission frequently required to specialized
◦◦ Addition of potassium once serum K unit or to the intensive care unit
< 5.0 mEq/L • Continued monitoring
◦◦ Addition of phosphate as potassium –– Hourly plasma glucose
phosphate as serum phosphate allows –– Hourly neurologic assessments
–– Prompt subspecialty consultation –– Hourly intake and output
–– Frequent laboratory monitoring –– Serial measurements of serum potassium,
–– Frequent neurologic assessments to moni- calcium, phosphate, magnesium
tor for cerebral edema –– Serial venous blood gas
Goals of treatment
Life-Threatening Complications • These goals are typically achieved in the
to Consider in the Emergency inpatient setting
Department –– Resolution of hyperglycemia
–– Correction of dehydration
• Cerebral edema –– Closure of anion gap acidosis (anion gap
• Shock/cardiovascular collapse normalized between 10 and 12)
–– Dehydration can be profound –– Oral tolerance to feeds
–– Requires prompt restoration of intravascu- –– Resolution of other symptoms
lar volume
–– Consider infection/sepsis as trigger for
stress response and hyperglycemia if clini- CONCUSSION/HEAD INJURY
cally warranted
• Hyperkalemia or hypokalemia
–– Obtain ECG in critically ill child Definition
–– May cause life-threatening arrhythmias or • Concussion can be defined as
cardiovascular collapse –– An acute injury to the brain from an exter-
• Profound metabolic acidosis nal physical force
–– Insulin infusion is necessary to stop pri- – – Resultant confusion, disorientation, brief
mary ketoacidosis loss of consciousness, self-limited post-
–– Insulin infusion should never be stopped in traumatic amnesia and/or other transient
DKA: If hypoglycemia occurs, adjust dex- neurologic abnormalities
trose in fluids or rate of fluids to maintain –– GCS score of 13–15 after 30 min following
plasma glucose levels the injury
• Hypophosphatemia • Also known as a mild traumatic brain injury
Epidemiology and mechanism of pediatric ◦◦ Confusion

concussions ◦◦ Difficulty concentrating
• Major cause across all age groups for pediat- ◦◦ Disorientation
ric visits to emergency care ◦◦ Persistent crying
• Arises from either a direct or transmitted –– Neurologic
blow to the head, face, or neck ◦◦ Headache
• Subsequent injury to the brain is the result of ◦◦ Dizziness
an interplay of pathophysiologic processes, ◦◦ Gait abnormalities
induced by biomechanical forces, without ◦◦ Sensitivity to light/noise
evidence of structural brain injury on stan- ◦◦ Slurred speech
dard neuroimaging ◦◦ Fatigue
–– Behavioral
Risk factors for a concussion ◦◦ Increased sleep
• An individual’s risk for a concussion is multi- ◦◦ Emotional lability
factorial with no single element being abso- –– Gastrointestinal
lutely predictive ◦◦ Nausea
–– Boys reportedly affected more than girls ◦◦ Vomiting
due to predilection for more injuries/inclu- ◦◦ Refusal to feed
sion in more sports-related activities
–– Girls more likely to report symptoms of Management
concussion • Diagnosis is typically clinical
–– History of ADHD or learning problems –– Neuroimaging is not routinely indicated
raises lifetime risk for a diagnosis of a concussion
–– History of prior concussion raises risk for ◦◦ For further considerations of head imag-
future concussion ing in association with pediatric head
trauma, see Trauma and Burns and
Risk factors for prolonged concussion Table 7.5 [1]
symptoms • Conservative management is the mainstay of
• An individual’s risk for prolonged symptoms treatment for pediatric concussions
is multifactorial with no single element being –– Antiemetics may be used for nausea and/or
absolutely predictive vomiting
–– Prior history of concussion-like symptoms –– Pain control with nonopioid medications
–– Known history of intracranial (e.g., ibuprofen and acetaminophen)
abnormalities –– Stepwise approach to cognitive and physi-
–– Psychiatric disorders, headache disorders cal rest (see Chap. 14 “Sports Medicine”)
–– Family and social stressors ◦◦ Complete bed rest may be required for a
–– Female sex predictive of symptoms lasting variable length of time (typically no
more than 4 weeks more than 2–3 days)
–– Older age ◦◦ Additional avoidance of activities that
have high cognitive load is based upon
Signs and symptoms the patient’s individual risk factors and
• The signs and symptoms of pediatric concus- developmental stage
sions are variable ◦◦ Gradual return to daily activities and
–– Cognitive increasing cognitive and noncontact
◦◦ Amnesia—may be retrograde or physical activity in a manner that does
anterograde not exacerbate symptoms
◦◦ Return to full activities only if patient is been unsupervised temporarily (usu-

asymptomatic and has passed prior ally for < 5 min)
stages of recovery ▪▪ Typical incidents involve a toddler
• Anticipatory guidance is important to man- left unattended temporarily or under
age expectations and promote recovery the supervision of an older sibling
–– Inadequately treated concussions can pro- –– Second peak: Occurs at ages 15–24 years
long symptomatology and place patient at ◦◦ Primarily male adolescents and young
risk for reinjury adults
–– Warnings signs and symptoms to watch for ◦◦ Most incidents occur in natural water
that could indicate more severe injury
–– Recovery time is unique to each patient Mechanism of injury
and for each incidence of head trauma • Initial progression of injury
–– Concussions can cause physical, cognitive, –– Swallowing of water
and psychological impairments ◦◦ Laryngospasm
◦◦ Loss of consciousness due to
hypoxemia
DROWNING ◦ ◦ Hypoxia
◦◦ Loss of circulation
Definition ◦◦ Tissue ischemia
• Drowning is defined as ◦◦ CNS injury (the most common cause of
–– The process of experiencing respiratory death)
impairment from submersion in a liquid • Secondary progression of injury
–– Avoid using confusing older terms: Near –– After nonfatal drowning, further complica-
drowning, secondary drowning, and wet tions can develop:
drowning –– Pulmonary
• Classification of drowning ◦◦ Aspiration pneumonia
–– Fatal ◦◦ Acute respiratory distress syndrome
–– Nonfatal with no morbidity (ARDS)
–– Nonfatal with morbidity (moderate, severe, –– Cardiac
vegetative state, brain death) ◦◦ Myocardial depression, arrhythmias
–– Neurologic
Epidemiology ◦◦ Cerebral edema, increased ICP
• Drowning is a major cause of injuries and –– Metabolic
death ◦◦ Metabolic and respiratory acidosis
–– Seasonal variation, with increasing inci- –– Hematologic
dence in summer months ◦◦ Hemolysis, coagulopathy
• Incidence follows a bimodal distribution –– Renal
–– First peak occurs in children < 5 years of ◦◦ Acute tubular necrosis
age
◦◦ Children < 1 year Management
▪▪ Often drown in bathtubs, buckets, and • At the scene
toilets –– Immediate cardiopulmonary resuscitation
▪▪ Over half of infants in bathtubs (CPR) once a submersion has occurred is
◦◦ Children 1–4 years of age the most important initial step
▪▪ Over half of young children drown in • Prompt attention to airway, breathing, and
swimming pools where they have circulation
• Early intubation if • Initial imaging

–– Signs of neurologic deterioration –– Chest radiograph: indicated for all patients
–– Inability to protect airway –– Head CT: may be indicated for patients
–– Inability to maintain adequate oxygenation presenting with AMS
or ventilation despite supplemental
oxygen Disposition
◦◦ Remember orogastric tube for gastric • If CPR is required at the scene, recommend
decompression if intubated admission regardless of clinical status upon
• Administer 100% oxygen immediately to presentation
maintain SpO2 > 94% • If patients with mild symptoms on arrival,
–– Prevent further hypoxemia and acidosis recommend admission for monitoring
• Support work of breathing • If patient is asymptomatic with the following
–– If patient does not require intubation but criteria, the patient may be monitored for
has signs of impaired gas exchange, can 6–8 h prior to discharge home with close fol-
elect to use noninvasive positive pressure low-up instructions
ventilation such as continuous positive air- –– GCS 15
way pressure (CPAP). –– Normal chest radiograph
–– If advanced airway is established, mechan- –– Normal lung exam
ical ventilation with positive end-expira- –– Normal oxygen saturations
tory pressure (PEEP) –– Safe home
• Judicious fluid and shock resuscitation
–– Especially important with high levels of Prevention and guidance
positive airway pressure required for ade- • Prevention is the key intervention in pediatric
quate ventilation with poor lung compli- drowning
ance, with resultant increased intrathoracic –– Installation of 4-sided fencing
pressure and decreased venous return to ◦◦ Completely prevents direct access to the
the heart pool from the house and yard
–– Vasopressors as indicated ◦◦ At least 4 ft high (or higher if required
–– After hemodynamic stability achieved, by local ordinance) and climb-resistant
severe drowning may require fluid restric- ◦◦ Distance from bottom to ground less
tion and diuretic therapy due to pulmonary than 4 in.
edema ◦◦ Gate should be self-latching and self-
• Cervical spine immobilization if suspected closing, with the latch placed at least
head/neck trauma is present 54 in. above the bottom of the gate, open
–– Classic example: Dive into shallow water away from the pool, and should be
• Serial measurements checked often
–– Cardiopulmonary monitoring, tempera- ◦ ◦ Effective in preventing more than 50%
ture, and neurologic assessments of swimming-pool drownings of young
◦◦ Pediatric drowning victims typically are children
hypothermic even if the water is warm • Supervision needs to be close, constant, and
◦◦ Abrupt change in mental status can capable
reflect worsening lung function and –– Never—even for a moment—leave small
hypoxemia children alone or in the care of another
• Initial laboratory studies young child while in bathtubs, pools, spas,
–– Point-of-care glucose, complete blood cell or wading pools or near irrigation ditches
count, electrolytes, urinalysis or other open standing water
–– A supervising adult with swimming skills • Hypertensive emergency

should be in the water, within an arm’s –– Significantly elevated BP with evidence of
length, providing “touch supervision” secondary organ damage (e.g., encepha-
–– With older children and better swimmers, the lopathy or left ventricular failure)
eyes and attention of the supervising adult –– Develops over hours
should be constantly focused on the child • Essential (primary) hypertension
–– The adult should not be engaged in other –– Hypertension in which no underlying dis-
distracting activities that can compromise ease is discovered
this attention, such as talking on the tele- –– Multifactorial causes
phone, socializing, tending chores, or –– Increasingly common due to increasing
drinking alcohol obesity, sedentary lifestyle, and poor diet
–– Children should never swim alone without –– Diagnosis of exclusion
an adult • Secondary hypertension
–– Result of underlying pathology
Swim lessons –– Many causes: cardiac, endocrine, toxic,
• Swim lessons for children > 4 years: renal, CNS
Recommended
• Swim lessons for children 1–4 years: Blood pressure (BP) measurement in
Insufficient data to recommend at this time pediatrics
• Manual BP with auscultation is ideal
Equipment –– If initial BP via automated BP cuff is abnor-
• Personal flotation devices (PFDs or life jack- mal, must repeat with manual reading
ets) are recommended • Appropriately sized BP cuff
• Air-filled swimming aids (inflatable arm –– Circumference completely encircles arm
bands, floaties) are not recommended with overlap
• Do not use air-filled swimming aids in place –– Bladder width ~40% of arm circumference
of PFDs ◦◦ Small cuff size can falsely elevate BP
readings
• Attempt to obtain when patient is calm and
HYPERTENSIVE CRISIS cooperative
–– Crying, fear, pain, anxiety, fever, and hun-
With climbing rates of obesity among children, ger can all falsely elevate BP readings
hypertension is now increasingly common among –– If initial BP is elevated and patient shows
children. This section will discuss an approach to no sign of end-organ failure, repeat mea-
children presenting with hypertension and make surement when patient has calmed
distinctions between hypertensive urgencies and
hypertensive emergencies (see Chap. 23 Secondary causes of hypertension
“Nephrology” for further details on hypertension • Kidney disease
in pediatric patients). –– Chronic kidney disease, nephritis, renal
artery stenosis, obstructive uropathy,
Definitions Wilms tumor, etc.
• Hypertensive urgency –– More frequent < 6 years of age
–– Significantly elevated BP with potential for • Cardiac disease
harm but without findings of end-organ –– Coarctation of the aorta (most common)
damage ◦◦ BP in right arm > 20 mmHg above lower
–– Develops over days to weeks extremity BP
–– Others: Abdominal aortic obstruction –– Neurologic exam: Mental status, cerebellar

(abdominal masses), inflammatory arteritis function
(e.g., Takayasu arteritis, vasculitis) –– Ophthalmologic exam: Disc edema, hem-
• Endocrine disease orrhage or infarct, visual acuity
–– Rare but highly treatable, with many poten- • Laboratory investigations
tial causes –– Initial investigations should be limited to
–– Examples: Congenital adrenal hyperplasia, basic interventions
familial hyperaldosteronism, hyperthy- –– CBC, electrolytes, BUN, serum creatinine,
roidism, hyperparathyroidism, pheochro- urinalysis and urine culture
mocytoma, Cushing syndrome, etc. –– Four-limb manual BP
–– Special note on neurofibromatosis type 1 –– ECG
(NF1) –– Further investigations must be targeted to
◦◦ NF1 is particularly known to have mul- the suspected secondary source of the
tiple potential causes for hypertension hypertension
◦◦ Association with renal artery stenosis, ◦◦ Example: Echocardiogram to evaluate
coarctation of the aorta, middle aortic for left ventricular hypertrophy and
syndrome, pheochromocytoma coarctation; Doppler renal ultrasound to
• Neurologic disease evaluate for renal artery stenosis
–– Many causes, including any intracranial • Initial interventions
process with increased ICP –– Attention to airway, breathing, and
–– Examples: Familial dysautonomia, circulation
Guillain–Barré syndrome, neuroblastoma –– Establish IV access
• Environmental/drug exposures –– Careful selection of a short-acting IV anti-
–– Many drugs, prescription and otherwise, hypertensive medication
can elevated BP ◦◦ The choice of antihypertensive must be
–– Common sources: Stimulants (pseudo- tailored to patient need, with consider-
ephedrine, caffeine, cocaine, amphet- ation of underlying disease process,
amines), oral contraceptives, potential drug–drug interactions, and
corticosteroids, anabolic steroids medication side effects
–– Medication withdrawal can also induce ◦◦ Avoidance of long-acting antihyperten-
hypertension sives to avoid overaggressive drop in
◦◦ Clonidine withdrawal BP and allow for tighter control of
therapy
Approach to severe hypertension presenting to ◦◦ Avoidance of enteral medications due to
emergency care variable effect and longer half-lives
• History and physical to evaluate for second- ▪▪ Enteral medications may be consid-
ary causes of hypertension ered in some cases of hypertensive
• Careful attention to signs of end-organ failure urgency
–– Cardiac exam: Signs of congestive heart –– Examples of IV pharmacologic options
failure, pulmonary edema, absent or ◦◦ Nicardipine
decreased femoral pulses, peripheral edema ▪▪ Calcium channel blockade
–– Abdominal exam: Palpable mass, audible ▪▪ Reduces peripheral vascular resistance
bruit
▪▪ Caution with intracranial processes, Table 7.12 Timeline for first hour management of pediatric
as can increase ICP septic shock
◦◦ Labetalol Timeline
▪▪ Alpha-1 and beta-blockade (min) Intervention
0–15 ABCs, cardiorespiratory monitoring,
▪▪ Reduces peripheral vascular resistance
supplemental oxygen, frequent blood pressure
▪▪ Contraindicated in asthma, conges- monitoring, strict intake and output, order
tive heart failure, heart block, or in intravenous access and labs
pheochromocytoma or cocaine over- 5–15 Obtain IV access, escalate to IO if unable to
dose (unopposed alpha effects) obtain IV
Labs: Blood culture, venous blood gas,
◦◦ Sodium nitroprusside
glucose, lactate, electrolytes, complete blood
▪▪ Potent and direct vasodilator count
▪▪ Strong arterial and venous smooth 0–20 Initial rapid fluid resuscitation of 20 mL/kg
muscle relaxant with instant onset normal saline fluid bolus
▪▪ Black box warning: Can cause cya- 0–60 Up to 3 fluid boluses with maximum 60 mL/
kg, reassessments after each additional bolus
nide toxicity (metabolized to thiocya- for attainment of clinical goals, have
nate and cyanide), must monitor vasopressor of choice ready for infusion,
thiocyanate levels monitor for need for intubation and
◦◦ Esmolol development of pulmonary edema
▪▪ Beta-1-blockade 0–60 Administer intravenous antibiotics within 1 h
60 Initiation of vasopressor of choice if fluid-
▪▪ Metabolism is independent of liver/ refractory shock, consideration of need for
kidney stress dose steroids, continual reassessments
▪▪ Contraindicated in asthma, heart block, > 60 Prompt transfer to pediatric ICU within 1 h
congestive heart failure
◦◦ Hydralazine SEPSIS AND SHOCK
▪▪ Arterial vasodilator
▪▪ Can cause increased ICP and fluid The first hour management of pediatric sepsis and
retention septic shock. Further details on sepsis and shock
◦◦ Phentolamine can be found in Chap. 8 “Critical Care.”
▪▪ Alpha-adrenergic antagonist
▪▪ Reserved for hypertension from cate- First-hour management of septic shock
cholamine excess, e.g., pheochromo- • Early recognition and resuscitation is key,
cytoma or cocaine toxicity although recognition is challenging
• Goals of therapy • Institutions benefit from implementing a sep-
–– Reduction of BP by < 25% in first 6–8 h sis screening tool and a sepsis intervention
◦◦ Cautious approach is warranted due to protocol (Table 7.12)
cerebrovascular autoregulation • Clinician assessment within 15 min
◦◦ Overaggressive drop in BP can put • Resuscitation begins within 30 min
patient at risk for brain ischemia
• Further management
–– Patients with hypertensive urgencies typi- PEARLS AND PITFALLS
cally require admission for further evalua-
tion and management Respiratory distress
–– Patients with hypertensive emergencies • In the search for a localizing problem for
typically require intensive care monitoring respiratory distress, remember to carefully
and resuscitation consider disorders external to the lung.
• A significant amount of non-airway disease • Prompt administration of intramuscular epi-

can cause respiratory distress via derange- nephrine is associated with lower risk of hos-
ment of either the respiratory system controls pitalization and fatality.
or acid-base status causing a secondary respi- • Delayed administration of epinephrine is
ratory compensation. associated with increased risk of hospitaliza-
• Be alert for abnormal breathing patterns in tion and worsened outcomes such as hypoxic-
the absence of abnormal auscultatory ischemic encephalopathy and death.
findings. • Antihistamines such as diphenhydramine
–– Bradypnea/tachypnea may signify relieve itching through H1-blocker effects but
increased ICP or CNS depression, as in do not help with airway or respiratory symp-
hypothermia, narcotic overdose, mass toms, hypotension, or shock.
lesion, meningitis, encephalitis, spinal cord • Inhaled bronchodilator therapy with alb-
injury or neuromuscular disease, or anxi- uterol can reverse bronchospasm but does
ety or pain. not help with angioedema, hypotension, or
–– Kussmaul respirations: acidosis (diabetic shock.
ketoacidosis). –– Keep in mind that epinephrine is also a
• “Not all that wheezes is asthma.” potent bronchodilator and will help relieve
• For patients with atypical or unexpectedly acute wheezing from anaphylaxis.
severe clinical presentations of what appears
to be an asthma exacerbation, always con-
sider less common intrathoracic pathology: Head trauma
–– Intrinsic lung disease (bronchopulmonary • Infants are at higher risk from mortality and
dysplasia, cystic fibrosis, pneumonitis, morbidity due to head trauma from nonacci-
lung malformations), heart failure, medias- dental trauma and may not have many signs
tinal masses, and GERD. or symptoms due to limited neurologic exams.
• Be alert for “red flag” warning signs that can • Always maintain a low threshold of suspicion
indicate imminent respiratory failure: for nonaccidental trauma.
–– Upper airway: tripoding, drooling, gur-
gling, inspiratory and expiratory stridor. Burns
–– Lower airway: grunting, head bobbing, • Always maintain a low threshold of suspicion
see-saw abdominal retractions. for nonaccidental trauma.
–– Neurologic: AMS, lethargy, extreme • “Red flag” warning signs that should raise
irritability. suspicion for abuse:
–– “Stocking and glove” distribution of burn:
The acute abdomen
Suggest forceful immersion of extremity in
• See Table 7.4 for Pearls and Pitfalls.
hot liquid.
–– Full thickness burns: Children typically
Anaphylaxis will retract extremity before this degree of
• The absence of skin findings does not rule out injury can occur.
anaphylaxis.
–– Many children will have only transient skin Inhalation injury
changes or rash. • Severe airway injury from smoke inhalation
• Anaphylaxis can present with primarily neu- can occur in the absence of external burn
rologic symptoms such as syncope. findings.
• Risks for smoke inhalation injury include • Unless there are signs of acute end-organ
young age and exposure within a closed dysfunction, treatment of hypertension in
space. pediatric patients is conservative.
• Due to risk for CO poisoning, early applica-
tion of 100% oxygen, blood gas analysis, and
carboxyhemoglobin level are important. Sepsis and shock
• Pediatric sepsis requires prompt recognition
Altered mental status and treatment.
• Broad differential diagnosis can make man- • Emphasis on first-hour fluid resuscitation and
agement of AMS a challenging diagnostic inotropic therapy with the following clinical
puzzle. goals:
• Careful attention to history and physical clues –– Improvement in heart rate.
and low index of suspicion for life-threaten- –– Normalization of BP.
ing disorders can help guide the differential –– Restoration of perfusion and pulses.
diagnosis. –– Reassessments after each bolus for signs of
• Many of the more common causes of AMS fluid overload.
are reversible if discovered promptly –– Antibiotic administration within first hour
–– Promptly identify and correct hypoglyce- of recognition,
mia, hypoxia, hypothermia, hypercarbia, –– Prompt transfer to the intensive care unit
and hypotension. for further support.
Foreign body ingestion and aspiration References

• Unwitnessed foreign bodies within the air-
way have the potential to masquerade as more 1. Kuppermann N, Holmes JF, Dayan PS, Hoyle
common diseases such as croup and bronchi- JD Jr, Atabaki SM, Holubkov R, Pediatric
olitis/asthma. Emergency Care Applied Research Network
• Esophageal foreign bodies have the potential (PECARN), et al. Identification of children at
to cause significant airway compromise. very low risk of clinically-important brain inju-
• Impaction is often to underlying pathology ries after head trauma: a prospective cohort
such as eosinophilic esophagitis, GERD, and study. Lancet. 2009;374(9696):1160–70.
known prior strictures. 2. Liang JL, Tiwari T, Moro P, Messonnier NE,
Reingold A, Sawyer M, Clark TA. Prevention
Drowning of pertussis, tetanus, and diphtheria with vac-
• Conduct careful assessment of all end-organ cines in the United States: recommendations
function in drowning victim. of the Advisory Committee on Immunization
• Underlying disease can be the precipitating Practices (ACIP). MMWR Recomm Rep.
cause for or a coexisting risk factor in a 2018;67(RR-2):1–44.
drowning event, e.g., toxic ingestion, inten- 3. Rupprecht CE, Briggs D, Brown CM, Franka
tional overdose, recreational drug use, seizure R, Katz SL, Kerr HD, Centers for Disease
disorder, cardiac arrhythmia, hypoglycemia. Control and Prevention (CDC), et al. Use of a
• Prevention of drowning is key. reduced (4-dose) vaccine schedule for postex-
posure prophylaxis to prevent human rabies:
Hypertensive crisis recommendations of the advisory committee on
• Hypertension in a young child or infant is immunization practices. MMWR Recomm Rep.
more likely to represent secondary hyperten- 2010;59(RR-2):1–9.
sion with identifiable cause.
4. Suguitan M. Rule of nines. CodeHealth, 5 Oct Anaphylaxis

2017. codehealth.io/library/article-85/rule-of-
nines/. Accessed 11 Dec 2018. Holmes JF, Lillis K, Monroe D, Borgialli D,
5. Hoffman RS, Nelson LS, Goldfrank LR, Kerrey BT, Mahajan P, Pediatric Emergency
Flomenbaum N, Howland MA. Goldfrank’s Care Applied Research Network (PECARN),
toxicologic emergencies. 10th ed. New York: et al. Identifying children at very low risk of
McGraw-Hill Education; 2015. clinically important blunt abdominal injuries.
6. Rumack BH, Matthew H. Acetaminophen poi- Ann Emerg Med. 2013;62(2):107–16.e2.
soning and toxicity. Pediatrics. 1975;55(6):871–6. Krishnamoorthy V, Ramaiah R, Bhananker
SM. Pediatric burn injuries. Int J Crit Illn Inj
Sci. 2012;2(3):128–34.
Suggested Reading Sicherer SH, Sampson HA. Food allergy: epidemi-
ology, pathogenesis, diagnosis, and treatment. J
Allergy Clin Immunol. 2014;133(2):291–307.
Respiratory Distress Sicherer SH, Simons FER, Section on Allergy and
Immunology. Epinephrine for first-aid manage-
Kämäräinen A. Out-of-hospital cardiac ment of anaphylaxis. Pediatrics. 2017;139(3).
arrests in children. J Emerg Trauma Shock. pii: e20164006.
2010;3(3):273–5. Stevenson MD, Ruddy RM. Allergic emergen-
Leung AK, Cho H. Diagnosis of stridor in chil- cies. In: Shaw KN, Bachur RG, editors. Fleisher
dren. Am Fam Physician. 1999;60(8):2289–96. & Ludwig’s textbook of pediatric emergency
Review. medicine. 7th ed. Philadelphia: Wolters Kluwer;
Weiner DL, Deanehan JK. Respiratory distress. 2016. p. 616–20.
In: Shaw KN, Bachur RG, editors. Fleisher
& Ludwig’s textbook of pediatric emergency
medicine. 7th ed. Philadelphia: Wolters Kluwer; Trauma and Burns
2016. p. 451–64.
Young KD, Gausche-Hill M, McClung CD, Lewis Holmes JF, Lillis K, Monroe D, Borgialli D,
RJ. A prospective, population-based study of Kerrey BT, Mahajan P, Pediatric Emergency
the epidemiology and outcome of out-of-hospi- Care Applied Research Network (PECARN),
tal pediatric cardiopulmonary arrest. Pediatrics. et al. Identifying children at very low risk of
2004;114(1):157–64. clinically important blunt abdominal injuries.
Ann Emerg Med. 2013;62(2):107–16.e2.
Krishnamoorthy V, Ramaiah R, Bhananker
Acute Abdomen SM. Pediatric burn injuries. Int J Crit Illn Inj
Sci. 2012;2(3):128–34.
Bachur RG. Abdominal emergencies. In: Shaw Liang JL, Tiwari T, Moro P, Messonnier NE,
KN, Bachur RG, editors. Fleisher & Ludwig’s Reingold A, Sawyer M, et al. Prevention of
textbook of pediatric emergency medicine. pertussis, tetanus, and diphtheria with vaccines
7th ed. Philadelphia: Wolters Kluwer; 2016. in the United States: recommendations of the
p. 1313–33. Advisory Committee on Immunization Practices
Reust CE, Williams A. Acute abdominal pain in chil- (ACIP). MMWR Recomm Rep: Morb Mortal
dren. Am Fam Physician. 2016;03(10):830–6. Wkly Rep Recomm Rep. 2018;67(2):1–44.
Rothrock SG, Pagane J. Acute appendicitis Menaker J, Blumberg S, Wisner DH, Dayan PS,
in children: emergency department diag- Tunik M, Garcia M, Intra-abdominal Injury Study
nosis and management. Ann Emerg Med. Group of the Pediatric Emergency Care Applied
2000;36(1):39–51.
Research Network (PECARN), et al. Use of the Toce MS, Burns MM. The poisoned pediatric
focused assessment with sonography for trauma patient. Pediatr Rev. 2017;38(5):207–20.
(FAST) examination and its impact on abdominal
computed tomography use in hemodynamically
stable children with blunt torso trauma. J Trauma Foreign Body Aspiration and Ingestion
Acute Care Surg. 2014;77(3):427–32.
Kramer RE, Lerner DG, Lin T, Manfredi M, Shah
M, Stephen TC, et al. Management of ingested
foreign bodies in children: a clinical report of
Status Epilepticus
the NASPGHAN Endoscopy Committee. J
Glauser T, Shinnar S, Gloss D, Alldredge B, Arya Pediatr Gastroenterol Nutr. 2015;60(4):562–74.
R, Bainbridge J, et al. Evidence-based guide-
line: treatment of convulsive status epilepticus
in children and adults: report of the guideline Diabetic Ketoacidosis
Committee of the American Epilepsy Society.
Epilepsy Curr. 2016;16(1):48–61. Agus MS, Dorney K. Endocrine emergencies.
Glissmeyer EW, Nelson DS. Coma. In: Shaw KN, In: Shaw KN, Bachur RG, editors. Fleisher
Bachur RG, editors. Fleisher & Ludwig’s text- & Ludwig’s textbook of pediatric emergency
book of pediatric emergency medicine. 7th ed. medicine. 7th ed. Philadelphia: Wolters Kluwer;
Philadelphia: Wolters Kluwer; 2016. p. 99–108. 2016. p. 690–717.
Kimia AA, Chiang VW. Seizures. In: Shaw KN, Cooke DW, Plotnick L, Cooke DW, Plotnick
Bachur RG, editors. Fleisher & Ludwig’s text- L. Management of diabetic ketoacidosis
book of pediatric emergency medicine. 7th ed. in children and adolescents. Pediatr Rev.
Philadelphia: Wolters Kluwer; 2016. p. 465–71. 2008;29(12):431–6.
Glaser N, Barnett P, McCaslin I, Nelson D,
Trainor J, Louie J, et al. Risk factors for cere-
Altered Mental Status bral edema in children with diabetic ketoaci-
dosis. The Pediatric Medicine Collaborative
Borgialli DA, Mahajan P, Hoyle JD Jr, Powell EC, Research Committee of the American Academy
Nadel FM, Tunik MG, Pediatric Emergency of Pediatrics. New Engl J Med. 2001;(4):264–9.
Care Applied Research Network (PECARN), Rosenbloom AL. The management of dia-
et al. Performance of the pediatric Glasgow betic ketoacidosis in children. Diabetes Ther.
coma scale score in the evaluation of children 2010;1(2):103–20.
with blunt head trauma. Acad Emerg Med.
2016;23(8):878–84.
Glissmeyer EW, Nelson DS. Coma. In: Shaw KN, Concussion/Head Injury
Bachur RG, editors. Fleisher & Ludwig’s text-
book of pediatric emergency medicine. 7th ed. Iverson GL, Gardner AJ, Terry DP, Ponsford JL,
Philadelphia: Wolters Kluwer; 2016. p. 99–108. Sills AK, Broshek DK, et al. Predictors of clini-
cal recovery from concussion: a systematic
review. Br J Sports Med. 2017;51(12):941–8.
Kuppermann N, Holmes JF, Dayan PS, Hoyle JD Jr,
Poisoning and Toxic Exposure Atabaki SM, Holubkov R, Pediatric Emergency
Care Applied Research Network (PECARN),
Hoffman RS, Nelson LS, Goldfrank LR, et al. Identification of children at very low risk
Flomenbaum N, Howland MA. Goldfrank’s of clinically-important brain injuries after head
toxicologic emergencies. 10th ed. New York: trauma: a prospective cohort study. Lancet.
McGraw-Hill Education; 2015. 2009;374(9696):1160–70.
Lumba-Brown A, Yeates KO, Sarmiento K, Hypertensive Crisis

Breiding MJ, Haegerich TM, Gioia GA, et al.
Centers for Disease Control and Prevention Constantine E, Merritt C. Hypertension. In: Shaw
guideline on the diagnosis and management KN, Bachur RG, editors. Fleisher & Ludwig’s
of mild traumatic brain injury among children. textbook of pediatric emergency medicine.
JAMA Pediatr. 2018;172(11):e182853. 7th ed. Philadelphia: Wolters Kluwer; 2016.
Lumba-Brown A, Yeates KO, Sarmiento K, p. 225–32.
Breiding MJ, Haegerich TM, Gioia GA, et al. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey
Diagnosis and management of mild traumatic D, Carroll AE, Daniels SR, et al; Subcommittee
brain injury in children: a systematic review. on screening and management of high blood
JAMA Pediatr. 2018;172(11):e182847. pressure in children. Clinical practice guideline
O’Brien MJ, Howell DR, Pepin MJ, Meehan WP for screening and management of high blood
3rd. Sport-related concussions: symptom recur- pressure in children and adolescents. Pediatrics.
rence after return to exercise. Orthop J Sports 2017;140(3). pii: e20171904. Erratum.
Med. 2017;5(10):2325967117732516. Pediatrics. 2018;142(3). pii: e20181739.
Drowning Sepsis and Shock

Brenner RA. Prevention of drowning in Balamuth F, Potts DA, Funari MK, Lavelle
infants, children, and adolescents. Pediatrics. J. Shock. In: Shaw KN, Bachur RG, editors.
2003;112(2):440–5. Fleisher & Ludwig’s textbook of pediatric emer-
Chandy D, Weinhouse GL. Drowning (submer- gency medicine. 7th ed. Philadelphia: Wolters
sion injuries). Danzi DF. UpToDate. Waltham: Kluwer; 2016. p. 605–10.
UpToDate. http://www.uptodate.com. Accessed Davis AL, Carcillo JA, Aneja RK, Deymann AJ,
13 Dec 2018. Lin JC, Nguyen TC, et al. American College
Idris AH, Bierens J, Perkins GD, Wenzel V, of Critical Care Medicine Clinical Practice
Nadkarni V, Morley P, et al. 2015 revised Parameters for hemodynamic support of pedi-
Utstein-style recommended guidelines for uni- atric and neonatal septic shock. Crit Care Med.
form reporting of data from drowning-related 2017;45(6):1061–93.
resuscitation: an ILCOR advisory statement. Howell MD, Davis AM. Management of sepsis
Resuscitation. 2017;118:147–58. and septic shock. JAMA. 2017;317(8):847–8.
Salomez F, Vincent JL. Drowning: a review of epi-
demiology, pathophysiology, treatment and pre-
vention. Resuscitation. 2004;63(3):261–8.
Critical Care
8
HISTORY AND PHYSICAL suggest serious infection, most likely

bacterial
EXAMINATION • Altered mental status
The importance of a well-performed history and –– For example, accidental ingestion, enceph-
relatively complete physical examination despite alitis, shock, or meningitis (fever and
the sophisticated available technology cannot be headache)
underscored enough. It can provide valuable infor- • Vomiting
mation guiding the practitioner to rapid recogni- –– For example, bowel obstruction (bilious
tion of the disease and its severity. vomiting is an ominous sign of possible
bowel obstruction), hydrocephalus (marked
increase in head circumference), incarcer-
History ated hernia, inborn errors of metabolism,
• Temperature or increased intracranial pressure
–– Hypothermia can frequently be linked to • Vomiting and/or abdominal pain
trauma, sepsis, intoxication, and –– For example, appendicitis, intussuscep-
hypothyroidism tion, testicular torsion, lower lobe pneumo-
–– Fever > 41 °C is frequently associated with nia, acute pyelonephritis, gastroenteritis or
invasive bacterial infection mesenteric adenitis (tends to improve with
–– Inconsolable crying, poor feeding, not time), or volvulus (usually the pain is pro-
waking up, grunting, seizures, and gressive, abnormal vital signs, lethargy,
decreased urine output usually indicate a abdominal distension, or bilious vomiting)
life-threatening illness like sepsis or • Respiratory distress
meningitis –– For example, asthma, pneumonia, bronchi-
–– In general, when fever defervesces, olitis, foreign body inhalation, retropha-
patients look better, are more active, and ryngeal abscess, epiglottitis, tracheitis, or
playful croup
–– Degree of fever, the presence of tachycar-
dia out of proportion to the fever, the pres- Physical examination
ence of tachypnea, and hypotension all • Head, eyes, ears, nose, and throat (HEENT):
Examine the head for signs of trauma like
scalp defects and laceration; palpate the ante-
rior and posterior fontanelle for fullness
M. K. Virk · M. H. Tcharmtchi (*)
Department of Pediatrics, Section of Critical Care, Baylor College –– Examine the eyes for swelling, redness,
of Medicine, Texas Children’s Hospital, Houston, TX, USA proptosis, eye movement limitation, and if
e-mail: mhtcharm@texaschildrens.org

248 M. K. Virk and M. H. Tcharmtchi
possible visual acuity. Check pupillary size • Common signs of shock: Lethargy, tachy-
and their reactivity to light, the retina, and cardia, cool or flushed extremities, poor or
optic disk. Check eyes and nose for abnor- bounding distal pulses, prolonged or flash
mal drainage (blood, cerebrospinal fluid) capillary refill time, mottled or pale skin
• Lungs: Observe the breathing pattern and • Bowel obstruction: Abdominal distension,
respiratory rate; auscultate for inspiratory tenderness, absent bowel sounds, bilious
stridor, grunting, coughing, retractions, nasal vomiting
flaring, or expiratory wheezing • Peritoneal irritation seen in appendicitis:
• Heart: Observe the heart rate, active precor- Abdominal tenderness and guarding (rup-
dium; auscultate the heart to detect the pres- tured appendix relieves the pain)
ence of murmur, pericardial friction rub, and
distant heart sound (pericardial effusion)
• Extremities: Palpate the extremities for MALIGNANT HYPERTHERMIA
warmth and swelling. Check the fingers and (MH)
toes for clubbing. Check distal pulses and
capillary refill time • Occurs in MH-susceptible patient
• Abdomen: Palpate and percuss the abdomen • MH is a hypermetabolic state when exposed
for distension, tenderness, and guarding. to a volatile anesthetic agent (such as haloge-
Auscultate for bowel sounds nated ethers like isoflurane, desflurane, and
• Neurologic: Check the posture and mental sevoflurane) or succinylcholine
status, Glasgow Coma Scale (GCS), deep • Its cause is due to unregulated passage of cal-
tendon reflexes, motor strength and tone, and cium from the sarcoplasmic reticulum into
cranial nerves II–XII the intracellular space
• More commonly observed clinical presenta-
Some common constellations of findings on tion in children: Sinus tachycardia, hypercar-
physical examination and potentially associated bia, and hyperthermia
diseases: • Less commonly observed findings: Masseter
• Increased intracranial pressure: Hyper- muscle rigidity, generalized muscle rigidity,
tension, bradycardia, and bradypnea (Cushing’s myoglobinuria, hyperkalemia, and EKG
triad) changes
• Transtentorial herniation—early signs:
Headache, altered mental status, small reactive Management of malignant hyperthermia
pupils, decorticate posturing, and Cheyne– • ABCD evaluation (airway, breathing, circula-
Stokes breathing (progressively deeper, and tion, and disability) per Pediatric Advanced
sometimes rapid breathing followed by apnea) Life Support (PALS) recommendations
• Transtentorial herniation—late signs: • Discontinue the triggering agent
Coma, pupils fixed and dilated in midposi- • Particularly on intubated patients, sudden
tion, decerebrate posturing, and ataxic breath- hypercarbia may be due to DOPE (displace-
ing (completely irregular breathing with ment, obstruction, pneumothorax,
apneic episodes) equipment)
• Uncal herniation: Unilateral third nerve • Optimize oxygenation and ventilation
palsy and unilateral fixed dilated pupils devi- • Treatment: Dantrolene
ating downward and laterally • Monitor and treat hyperkalemia
8 Critical Care 249
HEPATIC FAILURE • Most common cause of splenic rupture is

blunt abdominal trauma
• Hepatic dysfunction starts with nonspecific • Large amounts of blood can be lost leading to
prodromes hemorrhagic hypovolemic shock
–– Nausea and vomiting • Management of hemodynamically stable
–– Abdominal discomfort and/or swelling splenic rupture (grades 1–3) is conservative:
–– Malaise with or without fever –– Observation and monitoring
–– Symptoms may wax and wane for days to –– Serial hemoglobin and hematocrit
weeks • Hemodynamically unstable splenic rupture
–– It may not present with jaundice (grades 4–5) requires abdominal exploration
• Hepatic dysfunction may progress rapidly to • Management largely depends on the
hepatic failure institution
• Acute hepatic failure can start at any age and
in any clinical setting
• In two-thirds of the cases that require trans-
plantation, the cause of acute liver failure is INCREASED INTRACRANIAL
unknown PRESSURE (ICP)
• Signs and symptoms of impending hepatic
failure can be suspected by progression of • Increase in ICP is most commonly associated
–– Jaundice with the following conditions:
–– Rising liver enzymes, ammonia, and direct ––
Traumatic brain injury—most common
or conjugated bilirubin cause of elevated ICP in children
–– Encephalopathy from stage 0, without any –– Hydrocephalus
neurological symptoms, to stage IV with –– Brain tumors
coma –– Infection
–– Decreased synthetic function (factors V –– Hepatic encephalopathy
and VII have shortest half-lives) ––
Central nervous system venous outflow
–– Worsening coagulopathy, rising interna- impairment
tional normalized ratio (INR) and pro- –– Intractable refractory epilepsy
thrombin time (PT) • Chronic slow increase of ICP is usually well
tolerated
Management • Acute increase of ICP is a life-threatening
• Supportive condition requiring emergent intervention
• Treat the cause • Early recognition is key for improved neuro-
• Manage complications logic outcome
• If not reversible—liver transplantation
• Headache
SPLENIC RUPTURE • Vomiting
• Altered mental status and coma
• Potentially life-threatening condition • Acute onset of weakness
• Spontaneous atraumatic rupture is rare, e.g., • Papilledema—it takes several days to develop
infectious mononucleosis and neoplasm and can be absent in acute cases
• Hypertension with bradycardia or Management of patients with increased ICP

tachycardia and decrease in CPP
–– Cushing triad is a late sign of impending • Elevation of the head in midline to 15–30° to
herniation: Hypertension, bradycardia, allow for adequate venous drainage. Higher
and respiratory depression elevation may decrease CPP
• Less common findings include • Normothermia and normal blood sugar
–– Seizures • Maintain PCO2 between 35 and 40 mm Hg
• Normal intracranial pressure in adults is and avoid hypoxemia as both high PCO2 and
5–15 mm Hg low SpO2 cause vasodilation of cerebral vas-
–– It is lower in children and infants culature, leading to increase in CBF and
–– It is subatmospheric in newborns increase in ICP
• In general, ICP > 20 mm Hg should be treated –– Extreme hypocarbia leads to vasoconstric-
tion of brain vasculature, resulting in a
Management decrease in CBF causing further ischemia
• The initial management involves ABCD per –– Hypoxia or hypercarbia leads to vasodila-
PALS recommendations tion of brain vasculature and an increase in
–– Particular attention to D (disability) for CBF and further rise in ICP
signs of trauma or increased ICP • Seizures increase metabolic demand of the
• The major goal of management is to mini- brain and as a result increase in ICP
mize ICP and maintain adequate cerebral • Prophylactic anticonvulsants should be used
blood flow (CBF) for patients at high risk of developing
• Depending on the insult, the autoregulation seizures
of blood flow to the brain may be lost –– Severe traumatic brain injury
• Cerebral blood flow can be monitored with –– Depressed skull fractures
the cerebral perfusion pressure (CPP) –– Parenchymal injuries
• CPP = MAP (mean arterial pressure) minus • Adequate pain control is essential
ICP • Prevent hypotension and maintain adequate
• If jugular venous pressure (JVP) is higher MAP using 0.9% normal saline maintenance
than ICP, it should be used for calculating intravenous fluid (IVF) and bolus
CPP –– Avoid hypotonic solutions
–– All measurements are in mm Hg
• Normal CPP in adults range from 50 to Specific measures for intubated patients
70 mm Hg • Use lidocaine 1 mg/kg for intubation and
• The CPP is lower in children due to a lower when suctioning endotracheal tube (ETT) to
MAP diminish cough reflex
• There are no established ranges for children –– Cough causes a transient increase in ICP
–– Based on age, the normal accepted range is • Avoid using ketamine and succinylcholine
40–60 mm Hg • Elevate the head 15–30° and keep in midline
• The gold standard for ICP measurement is to allow for adequate venous drainage
intraventricular catheter • Tape ETT to the face and not around the neck
–– It has the advantage of cerebrospinal fluid • Keep positive pressure ventilation (positive
(CSF) drainage to treat an acute sudden end-expiratory pressure) [PEEP] and peak
increase of ICP inspiratory pressure [PIP]) to a minimum
8 Critical Care 251
while maintaining adequate oxygenation and short period of time until other more defini-
ventilation (maintain PCO2 between 35 and tive measures are introduced
40 mm Hg) –– Barbiturate coma
• Sedation and potentially neuromuscular –– Decompressive craniectomy
blocking to permit adequate ventilation and –– CSF drainage
oxygenation as well as decreasing metabolic • It will cause hypocarbia due to vasoconstric-
demand of the brain tion of brain vasculature and a decrease in
CBF causing ischemia
Hyperosmolar therapy
• There is limited evidence comparing manni- Dexamethasone
tol with hypertonic saline for treatment of • It is only recommended for vasogenic edema
acute signs of herniation or raised ICP caused by mass effect
• Mannitol –– Brain tumors
–– Rapidly distributed in extracellular space, –– Brain abscess
creating an osmotic gradient between
plasma and parenchymal tissue. To pro- Clinical findings associated with cerebral
duce an equilibrium, water shifts from edema
intracellular space to extracellular space • Asphyxial arrest is the most common type of
–– Osmotic diuresis of free water leads to cardiopulmonary arrest in infants and
increased serum sodium and osmolality children
–– There is a risk of hypovolemia • Cerebral edema can be the result of many
–– Does not cross an intact blood–brain types of injury to the brain leading to
barrier increased ICP. It can be classified into
–– Monitor serum osmolality; avoid using if 4 categories:
more than 320 mOsm/L • Vasogenic edema due to disruption of the
• Hypertonic 3% saline blood–brain barrier and extravasation of
–– There is limited evidence on the optimal protein
dosing and concentration –– Hydrostatic cerebral edema seen in acute
–– There is less risk of diuresis malignant hypertension
–– Can be given as continuous infusion –– Cerebral edema from brain neoplasms or
–– Target serum sodium level 145–155 mEq/L trauma
–– High-altitude cerebral edema due to fluid
Hypothermia leakage from the capillaries
• Clinical studies have demonstrated compara- • Cytotoxic edema where the blood–brain bar-
ble outcomes between therapeutic hypother- rier is intact
mia (32–34 °C) and targeted temperature –– Disruption in cellular metabolism damages
management at 36 °C the sodium–potassium pump leading to
• Targeted temperature management is sodium and water retention
preferable ◦◦ Cardiac arrest
◦◦ Severe hypothermia
Hyperventilation –– Disruption of sodium–calcium pump lead-
• It is used for treatment of acute sudden rise in ing to retention of calcium and sodium in
ICP or acute signs of brain herniation for a brain cells
• Osmotic cerebral edema –– Correction of electrolyte derangements

–– Plasma dilution due to syndrome of inap- such as potassium, sodium (135–
propriate antidiuretic hormone secretion 155 mEq/L), calcium, and glucose
(SIADH), water intoxication, and rapid –– Correction of hypotension and shock
decrease of glucose (diabetes ketoacidosis, –– Correction of hypothermia (above 35 °C)
hyperosmolar hyperglycemic state) –– Allowing adequate time for sedative, anal-
–– This creates an abnormal pressure gradient gesics, and neuromuscular blocking agents
between the brain (higher osmolality) and to be metabolized
plasma (lower osmolality) and movement • Brain death evaluation involves evaluation of
of water into the intracellular space neurological function, including brain stem
• Interstitial edema due to disruption of reflexes and apnea test
CSF–brain barrier • Two separate examinations are carried out
–– Obstructive hydrocephalus with spread of with an interval of 24 h for full-term infants
CSF into extracellular space up to 1 month of age; and 12 h apart for
–– In contrast to vasogenic edema, there is no infants from 1 month of age to 18 years
protein leakage • Absence of brainstem reflexes is defined as
• Symptoms of cerebral edema the presence of:
–– Headache –– Midposition fixed dilated pupils
–– Slurred speech bilaterally
–– Ataxia –– Absence of cough, gag, and corneal reflexes
–– Weakness –– Absence of spontaneous eye movements
–– Disorientation during oculovestibular and oculocephalic
–– Memory loss testing
–– Hallucinations or delusions –– Absence of any respiratory effort without
–– Seizures ventilatory support
–– Bradycardia • In addition, there should be a flaccid motor
–– Coma tone and lack of any spontaneous movement
or response to any tactile, visual, and verbal
stimuli
BRAIN DEATH • An apnea test is to be performed following
each neurological evaluation unless medi-
• Clinical criteria required to determine brain cally contraindicated:
death include deep unresponsive coma from –– Apnea test is performed off ventilator sup-
irreversible causes, loss of brainstem reflexes, port with supplemental oxygen at fraction
and loss of motor function (excludes spinal of inspired oxygen or FIO2 of 1 = 100%
reflexes) oxygen
––
Any reversible condition that interferes –– A positive test is defined as the lack of
with the interpretation of the examination respiratory effort when off the ventilator
must be previously excluded and rise in PaCO2 of 20 mm Hg above
• Close hemodynamic monitoring along with baseline or above 60 mm Hg
indwelling arterial catheter is necessary in • Death is declared after the second examina-
order to assure adequate oxygenation and tion confirms brain death
ventilation as well as for PaCO2 measurements • Apnea test should be aborted in patients
for apnea test requiring high- dose vasoactive agents and
• Prerequisite conditions to be fulfilled prior those who do not tolerate the test due to
to performing a brain death evaluation: hemodynamic instability or hypoxemia
8 Critical Care 253
• Radionuclide cerebral blood flow test is a Table 8.1 Common features of shock
commonly used ancillary study in most ICUs Cold shock Warm shock
utilizing portable gamma cameras. The study Cardiac dysfunction Vasoplegia
evaluates cerebral blood flow and its uptake Low cardiac output and high High cardiac output and low
SVR SVR
into the brain tissue Clinical presentation—common features
• Electroencephalogram has also been used to Tachycardia Tachycardia
identify the absence of any electrical activity Tachypnea Tachypnea
• Indications for performing ancillary tests: Hyper- or hypothermia Hyper- or hypothermia
–– When brain death evaluation and apnea Poor food intake Poor food intake
Not playful Not playful
test are not able to be completed due to Irritability Irritability
unstable clinical status Runny nose Runny nose
–– If medications or medical conditions inter- Increased SVR Decreased SVR
fere with brain death evaluation Impaired end-organ Impaired end-organ
perfusion: perfusion:
–– To reduce the interval observation period
Lethargy Lethargy
between the two examinations Cool extremities Warm extremities
–– If there is any concern about the validity of Weak distal pulses Bounding distal pulses
the examination Prolonged capillary refill Flash capillary refill
• If the ancillary test is inconclusive of the > 3 s (< 3 s)
Decreased urine output Decreased urine output
absence of cerebral blood flow or if the
Lactic acidosis Lactic acidosis
electroencephalogram (EEG) shows electri- Widened pulse pressure
cal activity, then observation period must be Low or normal blood Low blood pressurea
prolonged until the patient meets the crite- pressure a
ria for clinical brain death and apnea testing SVR systemic vascular resistance
or until another ancillary study can be Late sign due to compensatory mechanisms. It can remain
a
normal even with substantial compromise of the cardiovas-

repeated
cular system
COMMON CONDITIONS • Arterial oxygen content is the amount of oxygen

bound to hemoglobin plus the amount of oxygen
REQUIRING EMERGENCY CHILD dissolved in the arterial blood (usually minimal
SUPPORT and therefore negligible when calculating)
• Arterial oxygen content = (Hgb × 1.36 ×
Shock SaO2) + (0.003 × PaO2)
• Hgb g/dL, SaO2 = Percent arterial oxyhemo-
Definitions
globin saturation, PaO2 = arterial oxygen ten-
• Shock is a dynamic and unstable state that
sion (dissolved O2), and 1.36 = the amount of
can be life-threatening if not recognized in a
oxygen carried by 1 g of Hgb
timely manner. It is an imbalance between
oxygen delivery (impaired perfusion) and Stages of shock
tissue metabolic demands (Table 8.1) • Compensated
• Cardiac output is the product of stroke vol- –– During this stage of shock, vital organ
ume (SV) and heart rate (HR): CO (L/min) = functions are maintained by a number of
SV (L) × HR/min compensatory mechanisms like peripheral
• Oxygen delivery (DO2) is determined by car- vasoconstriction (increased systemic vas-
diac output (CO) and the arterial content of cular resistance, or SVR), leading to
oxygen (CaO2) = DO2 × CaO2 increased cardiac output
–– As a result, the blood pressure is usually –– Intraosseous access is safe, quick, and
normal. This can delay the recognition effective in children, and the frequency of
of shock and therefore timely interven- the complications is negligible
tion to reverse the process with the goal –– Ideal intraosseous placement in order of
of restoring normal tissue oxygen preference
delivery ◦ Tibial tuberosity (anteromedial surface
–– Hypotension develops usually late in of proximal tibia)
shock states with the exception of early ◦ Proximal humerus
distributive shock (sepsis) and neurogenic ◦ Femoral
due to peripheral vasodilation (decreased ◦ Iliac crest
SVR) • Except for cardiogenic shock, administer
–– If unrecognized or undertreated, compen- 20 ml/kg of isotonic fluid (0.9% sodium chlo-
sated shock progresses to decompensated ride or Ringer’s lactate) over the first 5–10 min
shock • Assess the patient after each bolus for further
• Decompensated need of fluid
–– At this stage, the compensatory mecha- • Evaluate for fluid overload—examine for
nisms are not sufficient to maintain the per- rales and hepatomegaly
fusion of the vital organs. It leads to • Check blood glucose and electrolytes
advanced end-organ dysfunction, cellular • Monitor end-organ perfusion
hypoxia, and irreversible organ damage –– Urine output
–– Outcome is poor despite appropriate resus- –– Mental status
citative measures • Central venous line, indwelling arterial line
and Foley catheter
Common management strategies • Imaging studies
• Successful management of shock depends on • Close monitoring of response to treatment
early recognition and accurate classification • Goal is to restore normal circulation to age-
based on clinical findings appropriate physiological parameters
• ABCD evaluation (airway, breathing, circula-
tion, and disability) per PALS
recommendations lassification of Shock
C
• Start oxygen—ideally high-flow nasal can-
nula in order to titrate FiO2 ypovolemic Shock
H
• In some cases, endotracheal intubation is • Most common type of pediatric shock. It is
necessary the consequence of extravascular (diarrhea)
–– It decreases the work of breathing and oxy- or intravascular (hemorrhage) fluid loss lead-
gen consumption due to respiratory ing to decreased preload
distress • Decreased preload in turn leads to a decline
• Continuous hemodynamic monitoring, in cardiac output
including heart and respiratory rate, blood • Clinical findings as outlined in Table 8.1
pressure, and oxygen saturation (SpO2) • Usually cardiac output is low—cold shock
• Obtain intravascular/intraosseous access per
PALS recommendations Specific management strategies
–– If intravascular access is unsuccessful after • In addition to common management strate-
3 attempts within 5 min, obtain intraosse- gies outlined before
ous access • The mainstay of treatment is rapid restoration
–– Do not delay treatment while waiting for of plasma volume and oxygen delivery to the
IV access tissues
8 Critical Care 255
• Multiple boluses of 0.9% sodium chloride or –– Congenital lesions resulting in significant

Ringer’s lactate 20–100 ml/kg of fluid may be left-to-right shunts (ventricular septal
required defects, truncus arteriosus, ALCAPA).
• Continuous fluid losses should be taken into They are typically present between 6 weeks
account when managing these patients and 3 months of age as pulmonary vascular
• Goal is to restore normal circulation to age- resistance (PVR) gradually falls after birth
appropriate physiological parameters –– Pneumothorax and cardiac tamponade
• For all patients who require more than 40 mL both prevent diastolic filling of the heart
per kilogram of bolus, the need for vasopres-
sor or inotropes should be considered Specific management strategies
• In addition to common management strate-
Cardiogenic Shock gies outlined before
• History of heart disease, poor feeding, exces- • The presentation of the cardiogenic shock
sive sweating, and poor weight gain may easily be missed or confused with other
• In addition to the common features outlined causes of shock
in Table 8.1 • Cardiogenic shock should be considered in
• Gallop rhythm, rales, jugular venous disten- patients whose condition worsens with fluid
tion, hepatomegaly therapy as initial management of shock
• Chest radiography (CXR) may show • Obtain electrocardiogram and echocardio-
cardiomegaly gram with any suspicion of cardiogenic shock
• Failure to meet the tissue oxygen demands • Routine laboratory investigations plus lactate
due to low cardiac output, inadequate pre- and B-type natriuretic peptide (BNP)
load, excessive afterload, intrinsic muscle • Do not delay treatment while waiting for
failure, or dysrhythmia echocardiogram
• For example, • Most children with poor cardiac function may
–– Depressed myocardial contractility (infec- be volume depleted. Judicious and slow
tion, toxins, severe hypocalcemia or administration of fluids (5–10 ml/kg) is para-
hyperkalemia) mount in these children
–– Arrhythmias (supraventricular tachycardia) • Use of inotropes such as dopamine, epineph-
–– Outflow obstruction from left heart (hypo- rine, or milrinone may be required
plastic left heart syndrome, aortic stenosis, • Goal is to restore normal circulation to age-
and coarctation of the aorta where femoral appropriate physiological parameters
pulses are usually absent or diminished as • Consider diuretics if volume overload is
well as lower blood pressure in the lower suspected
extremities compared with the right upper
extremity) istributive Shock: Septic Shock
D
–– Outflow obstruction from right heart (tri- • Systemic inflammatory response syndrome
cuspid atresia, pulmonary atresia, and (SIRS) criteria. The presence of 2 or more of
tetralogy of Fallot. All three are cyanotic the following criteria, one of which must be
congenital lesions that cause obstruction of abnormal temperature or white blood cell
the right heart outflow) (WBC) count
–– Myocarditis, pericarditis, and congenital –– Elevated or depressed WBC count
cardiomyopathies –– Fever > 38.5 °C or hypothermia < 36 °C
–– Coronary ischemia (anomalous left coro- –– Tachycardia or bradycardia
nary artery from the pulmonary artery –– Tachypnea
(ALCAPA))
• Sepsis: SIRS + suspected or proven infection ◦◦ Once central access available, titrate
• Severe sepsis: sepsis + either cardiovascular epinephrine to reverse cold shock; if epi-
or respiratory dysfunction; or > 2 other organ nephrine is unavailable, titrate central
systems dysfunction dopamine 5–10 mcg/kg/min. Titrate
• Septic shock: Sepsis and cardiovascular organ central norepinephrine 0.05–0.3 mcg/
dysfunction kg/min to reverse warm shock; use cen-
• In addition to the clinical presentations out- tral dopamine if norepinephrine is
lined in Table 8.1 unavailable
• Septic patients may present with vague symp- ◦◦ If shock is catecholamine resistant and if
toms or in overt septic shock at risk for adrenal insufficiency, start IV
• Can present as warm or cold shock hydrocortisone stress dosing at 100 mg/
• The majority of community-acquired septic m2 per day divided in 4 doses
shock presents as cold shock –– Advanced treatments 60 min and beyond
• Warm shock is seen in older children and ◦◦ Use central venous pressure, mean arte-
those with a central venous line rial pressure, and other additional mon-
itoring devices such as Doppler
Specific management strategies ultrasound, pulse index contour cardiac
• In addition to common management strate- output (PiCCO), thermodilution car-
gies outlined before diac output to titrate fluid, inotropic,
• Rapid recognition and initiation of treatment vasopressor, and vasodilator support
to restore normal circulation to age-appropri- ◦◦ If hemoglobin is less than 10 g/dL, trans-
ate physiological parameters fuse packed red blood cells
• Early intervention following the guidelines of ◦◦ If already on epinephrine and the blood
American College of Critical Care Medicine pressure is normal, ScvO2 (central
(ACCM) and PALS in the first 60 min. venous oxygen saturation) < 70% treat
• Fundamental features of the guidelines cold shock with milrinone infusion. Add
–– 0 to 5 min nitrovasodilators if SVR index is high
◦◦ Establish IV access. If unsuccessful, and/or the skin perfusion is poor.
establish an intraosseous (IO) line Consider levosimendan if shock
–– 5 to 15 min persists
◦◦ Isotonic saline bolus 20 ml/kg up to ◦◦ If already on epinephrine and the blood
60 ml/kg within the next 10 min with pressure is low, ScvO2 < 70%, treat
reassessment after each bolus. Stop cold shock with norepinephrine to
boluses if hepatomegaly or rales are obtain normal diastolic blood pressure.
present Consider dobutamine, enoximone, levo-
◦◦ Treat hypoglycemia and hypocalcemia simendan, or milrinone if shock
◦◦ Start antibiotics persists
◦◦ There is a linear increase in risk of mor- ◦◦ If already on norepinephrine and
tality for each hour delay in antibiotic euvolemic and the blood pressure is low,
administration ScvO2 > 70%, treat warm shock with
–– 15 to 60 min vasopressin, dobutamine, enoximone,
◦◦ Start epinephrine peripheral IV/intraos- and levosimendan
seous/intramuscular infusion (PIV/IO/ ◦◦ If shock persists, treat pericardial effu-
IM) at 0.05–0.5 mcg/kg/min for fluid sion and pneumothorax if present
refractory shock ◦◦ If shock remains refractory, consider
◦◦ Use atropine/ketamine PIV/IO, if needed extracorporeal membrane oxygenation
for central vein or airway access (ECMO)
8 Critical Care 257
–– The principles of rapid fluid expansion for • Unlike other forms of shock, neurogenic
septic shock may not apply in all settings, shock exhibits hypotension with bradycardia
particularly in developing countries
◦◦ The fluid expansion as supportive therapy Specific management strategies
study (FEAST) [1] showed that the fluid • In addition to common management strate-
expansion as outlined above may increase gies outlined before
harm in a resource-limited settings • Hypovolemia due to loss of sympathetic
venous tone and decreased preload should be
treated with 0.9% sodium chloride or Ringer’s
Anaphylactic Shock
lactate boluses
• In addition to the clinical presentations as • Stabilization of the spine
outlined in Table 8.1 • Computed tomography (CT) or magnetic res-
• Immunoglobulin E (IgE)–mediated onance imaging (MRI)
• Exposure to an allergen interacting with IgE • Neurosurgical consultation if trauma is
• Potentially life-threatening systemic reaction suspected
Specific management strategies bstructive Shock

O
• In addition to common management strate-
gies outlined before • Cardiac pump failure due to extracardiac causes
• Rapid recognition and initiation of treatment • Often associated with poor right ventricular
to restore normal circulation to age-appropri- output
ate physiological parameters • Pulmonary causes include pulmonary embo-
• Injection of IM epinephrine 0.01 mg/kg, lism and severe pulmonary hypertension
maximum 0.5 mg • Mechanical causes include tension pneumo-
• If no response, injection can be repeated thorax and pericardial tamponade
every 5–10 min • In addition to the clinical presentations as
• Occasionally the patient may require epi- outlined in Table 8.1
nephrine infusion • Depending upon the cause of obstructive
• Elevation of the lower extremity in supine shock, these patients may present with
position if tolerated –– Jugular vein distention
• Due to massive fluid shift, poor perfusion –– Hypotension
should be treated with isotonic solutions –– Pleuritic chest pain
• Inhaled albuterol for bronchospasms, –– Chest pain
0.15 mg/kg and repeat as needed –– Tracheal deviation
• H1 antihistamine–diphenhydramine 1 mg/kg –– Unilateral breath sounds
IV, maximum dose 40 mg –– Muffled heart sounds
• H2 antihistamine–ranitidine 1 mg/kg IV, –– Pulsus paradoxus
maximum dose 50 mg
• Glucocorticoids–methylprednisolone 1 mg/ Specific management strategies
kg IV, maximum dose 125 mg • In addition to common management strate-
gies outlined before
Neurogenic Shock • Fluid boluses to preserve preload
• Rare • Every attempt should be made to treat the
• Caused due to acute injury to the spinal cord underlying cause
or central nervous system resulting in loss of • Pericardiocentesis for cardiac tamponade
sympathetic venous tone • Chest tube placement for pneumothorax
• Clinical presentations as outlined in Table 8.1
Hemothorax and Flail Chest ediatric Acute Respiratory Distress

P
Syndrome (PARDS)
• Flail chest is defined as a condition with frac-
tures of 3 or more consecutive ribs or com- • PARDS is defined as an acute respiratory fail-
bined fracture of the sternum and ribs creating ure occurring within 7 days of a known clini-
an unstable injury and could be associated cal trigger (direct or indirect)
with hemothorax or pneumothorax requiring • New parenchymal infiltrates not fully
emergent drainage explained by cardiac failure or fluid overload
• Leads to impaired mechanics of the chest • Direct insult to the lung damaging the
wall wherein one segment of the chest moves alveoli
inward instead of outward during inspiration • Indirect injury causes primary destruction of
• Usually results from traumatic impact with the pulmonary endothelial barrier, resulting
high energy mechanism and is associated in interstitial edema
with high morbidity • Develops in the first 1–6 days after the initial
• There is high incidence of intrathoracic (pul- insult
monary contusions) and extrathoracic inju- • Results in decreased pulmonary compliance,
ries (traumatic brain injury) leading to arterial hypoxemia
• Less commonly seen in children compared to • May resolve completely without fibrosis
adults given the more compliant chest wall
Causes
Examination • Most common causes of direct injury are
• On examination, a characteristic paradoxical pneumonia (most common), aspiration pneu-
movement of the chest wall moving inward monitis, fat embolism, and submersion injury
rather than outward during inspiration and • Indirect causes include multisystem trauma,
outward instead of inward during exhalation sepsis, SIRS, and transfusion-related acute
is seen lung injury (TRALI)
• CXR and CT scan can identify rib fractures
and associated thoracic injuries Clinical presentation
• History of exposure to gaseous fumes or hydro-
Management carbon ingestion and potential aspiration
• Pain control, pulmonary toilet. Ensure ade- • Dyspnea due to increasing alveolar flooding
quate ventilation and oxygenation and decreasing pulmonary compliance
• Close cardiorespiratory monitoring is • Cough and fever
recommended • Severe pulmonary edema and abnormal gas
• Supplemental oxygen along with adequate exchange due to alveolar damage
pain control (regional nerve blocks along • Tachypnea, crackles, wheezing, diminished
with systemic analgesia) is standard of care air entry, mild to severe respiratory distress
• In severe cases with large pulmonary contu- with accessory muscle use
sions and ARDS, mechanical ventilation is • Signs of impending respiratory arrest may be
necessary noted such as bradypnea, tachycardia, altered
mental status, and cardiovascular collapse
• Tachypnea occurs in order to maintain ade-
ARDS quate minute ventilation
• Clinical entity of dyspnea, cyanosis resistant Investigations

to supplemental oxygen, and chest infiltrates • Arterial blood gas (pH, PCO2, PO2) with
on chest radiography without cardiac ailment lactate
8 Critical Care 259
• CXR—Essential for diagnosing • Arterial hypoxemia is an important feature of

ARDS. Radiographic findings immediately PARDS. Goal of PPV is to recruit alveoli by
after the inciting event may be entirely normal application of modest PEEP to reduce V/Q
or may show only the primary disease pro- mismatch, to allow adequate gas exchange
cess. As the disease progresses, the lung fields and reduce VILI
become diffusely and radiographically homo- • Judicious application of PEEP and limiting
geneously opaque. (ARDS is a non homoge- inflation pressures is paramount to the man-
neous disease process; however, this is not agement of PARDS
distinguishable on the CXR findings)
• Complete blood count (CBC) may reveal Principles of PPV in PARDS
leukocytosis • Different modes have been used to achieve
• Chemistry panel adequate ventilation and oxygenation
• Coagulation tests such as disseminated intra- –– There is no evidence showing superiority
vascular coagulation (DIC) panel of one mode to another
• Liver function tests and renal function tests • Titrate FIO2 and PEEP to maintain oxygen
(blood urea nitrogen [BUN], creatinine) to saturation above 88%, PaO 55–80 mm Hg,
monitor end-organ injury thus preventing biotrauma from excessive
• CT scan is often not possible, given the risk oxygen exposure
of life-threatening decompensation during • Limit alveolar plateau pressures to less than
transport and is unnecessary for the manage- 30 cm H2O to prevent barotrauma
ment of PARDS • Low tidal volumes (~ 4–6 ml/kg) allow per-
• Echocardiogram to determine cardiac func- missive hypercapnia while monitoring indi-
tion and to rule our intracardiac shunts ces of oxygen delivery and acid base balance
• Adequate PEEP to prevent stress-induced
Management alveolar injury by repetitive opening and
• Mainly supportive therapy aimed at treating closing of alveoli
the inciting cause and measures to reduce –– “Ideal PEEP” is where 0.6 FIO2 (to pre-
ventilator-induced lung injury (VILI) vent oxygen toxicity) affords adequate sat-
• Noninvasive mechanical ventilation is defined uration (> 88%)
as acute respiratory failure requiring full-face • If conventional mechanical ventilation fails,
bilevel positive airway pressure (BiPAP) or at transition to high-frequency oscillatory venti-
least a CPAP of ≥ 5 cm H2O with either a P/F lation (HFOV) pressures should be considered
ratio less than 300 to limit VILI from high inflation pressures
• P/F ratio = PaO2/ FIO2 • Neuromuscular blockade in the first 72 h should
• Endotracheal intubation as well as invasive be considered along with adequate sedation
monitoring is required in severe cases with and analgesia to reduce metabolic demand and
indwelling arterial catheters, central venous improve patient–ventilator synchrony
lines, and Foley catheter • If conventional therapies fail, ECMO should
be considered in candidates with reversible
Pulmonary causes of acute respiratory failure before they
• Early application of noninvasive PPV is rec- develop nonpulmonary organ dysfunction
ommended in an alert cooperative patient to and failure
aid alveolar recruitment
• Endotracheal intubation and mechanical ven- Cardiovascular complications
tilation are required in cases unresponsive to • Close monitoring of hemodynamic
noninvasive PPV parameters
• Fluid boluses with crystalloid, colloid, and • Inflammatory conditions causing serositis—
packed red blood cell transfusions are often Kawasaki disease, systemic lupus erythema-
required. Vasoactive infusions are often tosus, acute rheumatic fever
needed to maintain adequate cardiac output • Lymphatic anomaly causing chylous pericar-
dial effusions
Renal • Severe fluid overload associated with sys-
• Monitor urine output closely temic inflammatory response and multiorgan
• Early institution of diuretics and renal replace- failure
ment therapies should be considered to prevent
adverse effects of fluid overload on pulmonary Sign and symptoms
compliance (not in the acute phase of volume • Tachycardia
resuscitation, typically in the first 24–48 h) • Hypotension
• Wide pulse pressure
Gastrointestinal • Elevated central venous pressures
• Careful attention should be paid to early insti- • Pulsus paradoxus—exaggeration of systolic
tution of parenteral nutrition if enteral route is blood pressure decline of more than 10 mmHg
not feasible during inspiration
• Stress ulcer prophylaxis
Diagnosis
Infectious • Pericardial tamponade is a clinical diagnosis
• Broad-spectrum antimicrobial therapy • Echocardiogram will reveal pericardial fluid/
–– Antifungal and antiviral therapy should be air collection along with compression of right
considered, particularly in the immuno- atrium in diastole
compromised patient
Management
Others • Close hemodynamic monitoring
Prevention of venous thromboembolism and • Optimization of preload to augment cardiac
pressure ulcers output and improve perfusion by administration
of 0.9% sodium chloride or Ringer’s lactate
• Avoid diuretics, which could further decrease
Pericardial Tamponade effective arterial blood volume, worsening
hypotension
• Definition: the rapid accumulation of fluid or
• Avoid sedatives that would cause vasodila-
air in the pericardial space causing elevated
tion and further drop in cardiac output
pericardial pressure compressing the right
• Emergent pericardiocentesis to drain pericar-
atrium and impeding systemic venous return
dial fluid/air is the definitive therapy
leading to decreased preload resulting in
decreased cardiac output
• Life-threatening condition
EMERGENCY LIFE SUPPORT
• Early recognition and prompt management
are crucial
Endotracheal Tubes and Ventilatory
• Complications include obstructive shock and
cardiac arrest
Support
• Ventilatory management and selecting the
Causes appropriate endotracheal tube (ETT) size in
• Postcardiac surgery pediatric patients depends largely on the age
• Trauma and size
8 Critical Care 261
• ETT intubation selection according to inter- • Airway stimulation and activation of vagus
nal diameter (ID): nerve can cause increased secretion and
–– ETT size (uncuffed tubes) in infants: bradycardia
3–3.5 mm internal diameter –– Premedication with atropine or glycopyr-
–– ETT size (uncuffed) for 1–2 years of age: rolate may help to visualize the vocal
3.5–4.5 mm internal diameter cords
–– ETT size (uncuffed) for children more than • Successful ETT placement should be con-
2 years of age is determined by the for- firmed by colorimetric nonwaveform capnog-
mula: (mm ID) = (age in years/4) + 4 raphy. Auscultation and fogging of ETT are
–– For example, if the child is 8 years old, ID not adequate measures of confirmation
of ETT = 8/4 + 4 = 6 • Position of ETT should be 2 cm above the
–– Cuffed ETT size should be half to one size carina and below the first rib, usually at the
smaller than uncuffed or can use the follow- level of the second rib. The position should be
ing formula (mm ID) = (age in years/4) + 3 confirmed by CXR. The clavicles are not a
• When used appropriately, cuffed ETT is as reliable landmark of placement
safe as uncuffed ETT • Direct trauma is rare in the hand of the trained
• Backup ETT sizes in a half-size larger and specialist
half-size smaller should be readily available –– Pharyngeal and laryngeal damage
• ETT is typically inserted to the cm marking –– Damaged teeth, lips, and gums
corresponding to three times the internal
diameter of the tube
Common Indications
Unique pediatric considerations for Endotracheal Intubation
• If ETT is too large, it may cause damage to and Ventilatory Support
this area leading to subglottic injury and
resulting in stenosis Respiratory Failure (RF)
–– After extubation, it can cause inspiratory • Type I = hypoxemic respiratory failure
stridor and may potentially necessitate • Type 2 = hypercapnic respiratory failure
reintubation. In extreme cases, a tracheos- • Causes for RF:
tomy may be needed –– Ventilation abnormalities
• In contrast to adults, the narrowest part of the ◦◦ Respiratory muscle fatigue
pediatric trachea is below the glottis at the ◦◦ Chest wall abnormalities
level of cricoid cartilage and selection of the ◦◦ Neuromuscular disease
correct ETT size is important to prevent –– Decreased ventilatory drive
injury to the mucosa –– Increased airway resistance or obstruction
• If the ETT is too small, it compromises the abil- –– Oxygenation abnormalities
ity to ventilate and oxygenate due to the “leak” ◦◦ Refractory hypoxemia
• Positioning of the ETT is as important as the ◦◦ Acute lung injury and ARDS
size selection—see above ◦◦ Need for PEEP (pulmonary edema or
• Right main stem intubation leads to total col- hemorrhage)
lapse of the left lung, desaturation, and hyper- ◦◦ Excessive work of breathing
ventilation of the right lung
• Intubation of the esophagus
Other common indications
–– Can lead to distension of the stomach and
• To decrease systemic myocardial oxygen
aspiration of gastric content
consumption
–– If unrecognized, has life-threatening
• To decrease left ventricular afterload
consequences
• To improve oxygen supply to meet the –– VT is determined by preset volume

demand (shock, cardiac arrest) –– MV is guaranteed
• To protect the airway –– PIP varies and depends on the compliance
–– Inability to control secretions of the respiratory system
–– Traumatic brain injury –– PIP limit should be set 5–10 cm H2O higher
–– GCS score < 8 than patient’s generated PIP. Frequent
–– Intoxications causing altered mental status assessment is required to monitor PIP; if
and loss of protective airway reflexes consistently higher than the limit, consider
changing the mode
Common modes of ventilatory support (Table 8.2) –– Typically, PIP should be kept below 35 cm
• Mechanical ventilation—invasive positive H2O
pressure ventilation (PPV)
• There are several mechanical ventilation Initial approach to setting ventilator parame-
modalities. The following is a brief descrip- ters (see Table 8.2)
tion of the 2 most commonly used modes • Choose a familiar mode. Two commonly used
• Pressure control mode: modes of conventional mechanical ventila-
–– Delivers preset pressure, rate, and inspiration are:
tory time with decelerating inspiratory flow 1. Volume control synchronized mandatory
–– Tidal volume (VT) is determined by preset intermittent ventilation (SIMV)
pressure and the compliance of the respira- –– VT (VT = 6–8 cc/kg, assure proper chest
tory system rise, may need more for obese patients)
–– Minute ventilation (MV) is not guaranteed ◦◦ PIP varies and depends on the compli-
–– Frequent assessment is required to assure ance of the respiratory system
the desired MV delivery, as any decrease in ◦◦ Typically, PIP should be kept below
compliance will decrease VT and MV = 35–40 cm H2O
hypoventilation –– Rate (bpm) depending on the age and the
–– Typically, the preset pressure should be disease process
kept below 35 cm H2O ◦◦ Start at the rate according to the patient
• Volume control mode: age range
–– Delivers preset tidal volume, inspiratory ◦ ◦ Lower rate is desired for patients with
time, and rate with constant inspiratory flow asthma to allow complete exhalation
–– FIO2—start at 1 (100% oxygen)
Table 8.2 Modes of mechanical ventilation –– PEEP (cm H2O), depending on the disease
Parameter Pressure control Volume control process
Tidal volume Variable Constant ◦◦ Intubation results in the loss physiologi-
PIP (peak Limited Variable cal PEEP by ETT bypassing the larynx.
inspiratory A minimum PEEP is always required to
pressure)
Ti Preset Preset
keep alveoli open
Respiratory Preset Preset ◦◦ Usual starting point is 3–5 cm H2O
rate –– Inspiratory time Ti (s) is age and disease
Flow pattern Decelerating Constant dependent
(square wave) ◦◦ Increasing Ti will increase mean airway
Advantages Decelerating flow allows Decreases
alveolar recruitment, volutrauma pressure and improve oxygenation
prevents overdistention, Guarantees set ◦ ◦ Remember increasing Ti will decrease
and decreases barotrauma minute expiratory time
ventilation
8 Critical Care 263
–– Pressure support (cm H2O) in addition to PEEP and ARDS

PEEP. When taking spontaneous breaths
on the ventilator, the pressure support • PEEP plays an important role in the lung pro-
assists to overcome the resistance in tective strategy
the ETT and the ventilator tubing, help- • Increase in PEEP results in an increase of mean
ing with airflow easing spontaneous airway pressure, improving oxygenation
respiration. –– The key is to keep the alveoli open while
◦◦ Start at 5–10 cm H2O preventing overdistention
–– SIMV allows patient to take spontaneous –– The ideal goal is to keep the respirations
breaths, maintaining synchrony between on the portion of the loop with the optimal
the ventilator and the patient pulmonary compliance–functional residual
2. Pressure control SIMV and its variables capacity (FRC)
are the same as above, except – – At this point, minimum pressure is needed
–– PIP (starting point 20–25 cm H2O) with to expand the lungs
close monitoring of the chest rise. –– In general, the “ideal PEEP” is where 0.6
Increase as needed to achieve appropriate FIO2 (to prevent oxygen toxicity) affords
chest rise adequate saturation (> 88%)
–– VT is determined by the compliance of the
respiratory system
C ARDIOPULMONARY
ommon Special Ventilator Settings
C RESUSCITATION (CPR): AHA
and Strategies to Prevent VILI GUIDELINES
• Permissive hypercapnia is a ventilator strat- Chest compression rate
egy in the management of severe acute respi- • For infants, children, and adults: 100–120/min
ratory failure and ARDS • The recommended sequence per
–– In contrast to hypoxemia, hypercapnia is PALS guidelines (2015) is C-A-B-D:
not life-threatening circulation–airway–breathing–defibrillate
–– The tidal volume/pressure is lowered delib- • Allow the chest wall to recoil completely
erately, resulting in hypoventilation after each compression to improve venous
–– It minimizes lung damage caused return to the heart
by repetitive opening and stretching of • The goal of the compressions is to reach a coro-
the alveoli, preventing barotrauma/ nary perfusion pressure of 15 mm Hg (adult data)
volutrauma –– This pressure has been linked to successful
–– This strategy results in a lower pH and return of spontaneous circulation
higher PCO2 –– There is no such threshold established for
–– Over time, the pH improves, as this respi- children
ratory acidosis will be compensated by the –– It requires the presence of arterial and cen-
kidneys tral venous pressure monitoring catheters
–– For example, in ARDS, with this lung pro-
Chest compression depth
tective strategy, the VT can be decreased to
• Infant
4–6 cc/kg
–– At least one-third the depth of the chest
–– This is discussed further above in the
• Newborn
ARDS section
–– At least one-third the depth of the chest
–– About 4 cm Automated external defibrillator (AED)—AHA

• Child 1 year of age to puberty recommendations
–– Lower third of the sternum • Use AED for children between 1 and 8 years
–– At least one-third the depth of the chest in cardiac arrest
–– About 5 cm • Mainly for out-of-hospital arrest
• Adolescent (after puberty) • Use pediatric pads and pediatric dose attenu-
–– Like adults ator (for small children) to deliver the correct
–– Lower third of the sternum dose of shock
–– About 5–6 cm • If not available, do not delay treatment
while waiting for pediatric pads and pediat-
Chest compression techniques ric dose attenuator, instead use adult pads
• Infant and newborn—lone rescuer and AED
–– 2-finger compression method to compress • The pads should be placed according to the
the newborn and infant sternum just below drawing on the pads
the intermammary line • They should not come in touch or overlap
• Infant and newborn—two healthcare • For infants, use manual defibrillation to
providers deliver an accurate dose
–– 2-thumb-encircling-hands chest compression –– If not available, use pediatric pads and
–– 2 thumbs are placed together on the ster- pediatric dose attenuator to deliver the cor-
num to depress the sternum while the other rect dose of shock
fingers of both hands spread to encircle the –– If not available, do not delay treatment
thorax while waiting for pediatric pads and pedi-
–– The thumbs can be placed side by side or atric dose attenuator, instead use adult
they can overlap pads
–– This technique provides a better depth of • Follow the instructions of the AED
compression and therefore a better coro-
nary perfusion pressure compared to lone
rescuer technique PEARLS AND PITFALLS
• Child 1 year of age to puberty
–– Use 1 or 2 hands, whichever is preferable • Treatment of shock should not be delayed
to achieve the goal depth until hypotension (late sign) develops. Do not
• Adolescent (after puberty) delay treatment waiting for IV access.
–– Adult 2-hand technique • When measuring CPP: use intracranial pres-
–– Heel of the hand on the chest sure or JVP, whichever is higher.
–– Heel of the other hand on the top of the first • Do not administer benzodiazepines to patients
hand with hepatic failure.
–– Keep arms straight and shoulders directly • Asphyxial arrest is the most common type of
over the hands cardiopulmonary arrest in infants and
children.
Chest compressions to breath ratios • There are four types of cerebral edema: vaso-
• Lone rescuer 30:2 genic, cytotoxic, interstitial, and osmotic.
• Two rescuers 15:2 • Apnea test—Two separate examinations are
• When patient is intubated, this ratio does not carried out with an interval of 24 h for full-term
apply infants up to 1 month of age; and 12 h apart for
infants from 1 month of age to 18 years.
8 Critical Care 265
• There are four types of shock: hypovolemic, Burri PH, West JB, Crystal RG. Postnatal devel-
cardiogenic, distributive, and obstructive. opment and growth. In: Crystal RG, West
• Pericardial tamponade is defined as the rapid JB, editors. The lung: scientific foundations,
accumulation of fluid or air in the pericardial vol. 2. Philadelphia: Lippincott-Raven; 1997.
space causing elevated pericardial pressure p. 1013–26.
compressing the right atrium and impeding de Caen AR, Berg MD, Chameides L, Gooden CK,
systemic venous return, leading to decreased Hickey RW, Scott HF, et al. Part 12:Pediatric
cardiac output. Advanced Life Support: 2015 American
• Cardiac tamponade is a clinical diagnosis. Heart Association Guidelines Update for
• Children have higher oxygen consumption Cardiopulmonary Resuscitation and Emergency
compared to adults and are prone to hypoxemia; Cardiovascular Care. Circulation. 2015;132(18
hence, ensuring adequate oxygenation prior to, Suppl 2):S526–42.
during, and after the intubation is crucial. Critical Care Review: Pediatric. Mount Prospect,
• For CPR, the recommended sequence IL; 2018. http://www.sccm.org/Education-
per PALS guidelines is C-A-B-D: Center/Critical-Care-Review-Pediatric.
circulation–airway–breathing–defibrillate. Accessed 15 Sep 2018.
• In CPR, allow the chest wall to recoil com- Drutz JE. The pediatric physical examination.
pletely after each compression to improve In: Post TW, editor. UpToDate. Waltham:
venous return to the heart. UpToDate. http://www.uptodate.com. Accessed
15 Sep 2018.
Ferrer R, Martin-Loeches I, Phillips G, Osborn TM,
References Townsend S, Dellinger RP, et al. Empiric antibi-
otic treatment reduces mortality in severe sepsis
1. Maitland K, Kiguli S, Opoka R, Engoru C,
and septic shock from the first hour: results from
Olupot-Olupot P, Akech S, FEAST Trial Group,
a guideline-based performance improvement
et al. Mortality after fluid bolus in African children
program. Crit Care Med. 2014;42(8):1749–55.
with shock. N Engl J Med. 2011;364:2483–95.
Khemani RG, Smith LS, Zimmerman JJ, Erickson
S, Pediatric Acute Lung Injury Consensus
Suggested Reading Conference Group. Pediatric acute respiratory
distress syndrome: definition, incidence, and epi-
Ad Hoc Statement Committee. American Thoracic demiology: proceedings from the Pediatric Acute
Society: mechanisms and limits of induced post- Lung Injury Consensus Conference. Pediatr Crit
natal lung growth. Am J Respir Crit Care Med. Care Med. 2015;16(5 Suppl 1):S23–40.
2004;170(3):319–43. Nakagawa TA, Mudit M. The determination of
American Heart Association. Web-based integrated brain death. In: Nichols DG, Shaffner DH, edi-
guidelines for cardiopulmonary and emergency tors. Rogers’ textbook of pediatric intensive
cardiovascular care – part 12. Pediatric advanced care. 5th ed. Philadelphia: Wolters Kluwer;
life support. https://eccguidelines.heart.org/ 2016. p. 1066–76.
index.php/circulation/cpr-ecc-guidelines-2/ Nelson P, Litman RS. Malignant hyperthermia
part-12-pediatric-advanced-life-support/. 26 in children: an analysis of the North American
Sep 2018. Accessed 21 Sep 2018. malignant hyperthermia registry. Anesth Analg.
Bronicki RA, Price J. Cardiogenic shock. In: Kline 2014;118(2):369–74.
MW, editor. Rudolph’s pediatrics. 23rd ed. Nguyen TC, Carcillo JA. Pathophysiology of sep-
New York: McGraw-Hill Education; 2018. sis. In: Kline MW, editor. Rudolph’s pediatrics.
23rd ed. New York: McGraw-Hill Education; Tzelepis GE, McCool FD. The respiratory system
2018. and chest wall diseases. In: Murray JF, Nadel
Oliveira CF, Oliveira DSF, Gottschald AFC, et al. JA, Broaddus VC, Mason RJ, Ernst JD, King Jr
ACCM/PALS haemodynamic support guide- TE, et al., editors. Murray and Nadel’s textbook
lines for paediatric septic shock: an outcomes of respiratory medicine. 6th ed. Philadelphia:
comparison with and without monitoring cen- Elsevier; 2016. p. 1707–1722.e4.
tral venous oxygen saturation. Intensive Care Ventre KM, Arnold JH. Acute lung injury and
Med. 2008;34(6):1065–75. acute respiratory distress syndrome. In: Nichols
Pomerantz W. Pathophysiology and classifica- DG, Shaffner DH, editors. Rogers’ textbook of
tion of shock in children. In: Post TW, editor. pediatric intensive care. 5th ed. Philadelphia:
UpToDate. Waltham: UpToDate. http://www. Wolters Kluwer; 2016. p. 766–93.
uptodate.com. Accessed 15 Sep 2018. Waltzman M. Initial evaluation and manage-
Sackett DL, Rennie D. The science of the ment of shock in children. In: Post TW, editor.
art of the clinical examination. JAMA. UpToDate. Waltham: UpToDate. http://www.
1992;267(19):2650–2. uptodate.com. Accessed 15 Sep 2018.
Singer M, Deutschman CS, Seymour CW, Ware LB, Matthay MA. The acute respira-
Shankar-Hari M, Annane D, Bauer M, et al. tory distress syndrome. N Engl J Med.
The third international consensus definitions 2000;342(18):1334–49.
for sepsis and septic shock (Sepsis-3). JAMA. Wesson DE, Cox CS Jr. Thoracic injuries. In:
2016;315(8):801–10. Coran AG, Adzick NS, editors. Pediatric sur-
Tasker R. Elevated intracranial pressure in chil- gery. 7th ed. Philadelphia: Elsevier Mosby;
dren. In: Post TW, editor. UpToDate. Waltham: 2012. p. 271–88.
UpToDate. http://www.uptodate.com. Accessed
15 Sep 2018.
Infectious Diseases
9
Matthew B. Laurens
PUBLIC HEALTH Common organisms in childcare centers

• Shigella infection
CONSIDERATIONS: –– Transmitted from infected feces (person-
PREVENTION OF INFECTIOUS to-person contact)
DISEASES –– Do: Stool bacterial cultures for any symp-
tomatic contact
Infection Control and Prevention –– Know: If Shigella infections are confirmed,
administer appropriate antibacterial
Childcare Centers treatment
–– Return to childcare center if diarrhea has
• Immunization: Required for all enrollees and resolved and stool culture is negative
staff • Nontyphoidal Salmonella species
• Assist children with toileting and hand –– No antibiotic is required except:
hygiene ◦◦ Infants younger than 3 months of age
–– Hand washing with soap and water, alco- ◦◦ Immunocompromised host
hol-based antiseptic is acceptable if –– Infected individuals should be excluded
> 24 months old from childcare until symptoms resolve
–– Careful food preparation and diaper • Salmonella serotype Typhi
changing –– Treatment is indicated for infected
–– Disinfecting environmental surfaces pre- individuals
vents diarrheal diseases –– Return to childcare center
–– Respiratory etiquette (sneeze or cough into ◦◦ 5 years of age or younger: 48 h after
elbow) antibiotic treatment
• Exclusion and return policies: ◦◦ Older than 5 years: 24 h after the diar-
–– Use gloves when contacting body fluids rhea has resolved
–– Do not exclude because of lice, ringworm, • Other risk of infection: e.g., Giardia; rotavi-
conjunctivitis without fever or behavior rus; cryptosporidiosis; respiratory syncytial
change, rash without fever virus (RSV); parainfluenza virus; adeno,
M. B. Laurens (*)
Division of Infectious Diseases and Tropical Pediatrics,
Department of Pediatrics, Center for Vaccine Development and
Global Health, University of Maryland School of Medicine,
Baltimore, MD, USA
e-mail: mlaurens@som.umaryland.edu

268 M. B. Laurens
rhino, and corona viruses; Haemophilus influ- –– Negative pressure airborne infection isola-
enzae, pneumococcal, hepatitis A, and cyto- tion room
megalovirus infections –– Room air needs 6–12 changes per hour or
recirculation through a high-efficiency par-
Hospital and Office ticulate air (HEPA) filter
–– Certified N95 fine particle respirator mask
• Standard precautions are indicated in the care or similar sealing mask
of all patients including:
–– Hand hygiene before and after each patient P revention of Infection Through
contact Breastfeeding
–– Protective equipment when needed
• Exclusive breastfeeding for the first
Preventive methods 4–6 months is recommended by American
• Alcohol-based products preferred because of Academy of Pediatrics (AAP)
their superior activity and adherence • Interrupt breastfeeding for:
• Soap and water are preferred when hands are –– Breast abscess or cellulitis with direct con-
visibly soiled or exposed to a spore-forming tact with infant’s mouth; can continue on
organism (Clostridium difficile is the most other side
common), or for norovirus –– Women with tuberculosis (for first 2 weeks
• Gloves, isolation gowns, masks, and goggles of treatment, then acceptable)
for any exposure to body fluids, contaminated –– Maternal HIV (except in resource-limited
materials, and sharps settings)
• Strict aseptic technique for all invasive proce- –– Maternal human T cell lymphotropic virus
dures and for catheter care (HTLV) types 1 or 2
• Separate well and sick children areas in medi- • Do not interrupt for maternal hepatitis B
cal offices
Immunologic characteristics of breast milk
Examples of infections and agents requiring • Postpartum colostrum contains high concen-
transmission-based precautions trations of antibodies and other infection-pro-
• Contact precautions, e.g., RSV, C. difficile, tective elements
other infectious diarrhea, and Staphylococcus • The actual antibodies against specific micro-
aureus bial agents present in an individual woman’s
–– Gloves and gowns are required when there milk depends on her exposure and response
is direct patient contact to the particular agents
• Droplet precautions, e.g., influenza, Neisseria • Lactoferrin: Limits bacterial growth by iron
meningitidis, mumps, and Bordetella chelation
pertussis • Lysozyme: Bacterial cell wall lysis
–– Use of a surgical mask is required • Lactalbumin: Enhances Bifidobacterium
–– A single room is preferred growth and modulates immune system
–– Remember all office and hospital staff • Casein: Limits adhesion of bacteria and facil-
should receive an annual influenza itates the growth of Bifidobacterium
immunization • Carbohydrates: Enhance the growth of
• Airborne precautions, e.g., Mycobacterium probiotics
tuberculosis, measles, varicella (with contact • Lipids: Lytic effect on many viruses and are
precautions), severe acute respiratory syn- active against Giardia
drome (SARS)
9 Infectious Diseases 269
Absolute contraindication of breastfeeding • Cryptosporidium is most common cause of rec-

• Maternal HIV infection (except in resource- reational water-associated outbreaks; Giardia is
limited settings) second, also Shigella is another cause
• HTLV1 and HTLV2 • Regularly test home pools for pH, free chlo-
• Tuberculosis (active, untreated pulmonary rine, or bromine
tuberculosis, until effective maternal treat- • People with diarrhea should not participate in
ment for the initial 2 weeks or the infant is recreational water activities
receiving isoniazid) • Children with diarrhea should avoid swim-
• Herpes simplex virus (HSV) infection on a ming for 2 weeks after cessation of diarrhea
breast (until the lesions are cleared) (for Cryptosporidium)
• Breast abscess or cellulitis with direct contact • Avoid water ingestion
with infant’s mouth; can continue on other • Clean the child with soap and water before
side swimming
• Change diapers in the bathroom
Prevention of Vector-Borne Disease
• Chemoprophylaxis before traveling to Antimicrobial Resistance

endemic areas, e.g., atovaquone/proguanil for
malaria should be given before traveling to • Use of antimicrobials is the most important
endemic areas factor that leads to antimicrobial resistance,
• Use mosquito netting (bed-net) during sleep including in patients and in agriculture
in tropical areas • Diseases for which antibiotics are not appro-
• Use protective clothing priate: Nonspecific cough, bronchitis, viral
• Repellents, e.g., DEET (> 20%) applied to pharyngitis, common cold
children should be used to prevent tick and
mosquito bites
Infections in Immunocompromised Hosts
–– Insecticide should not be applied to chil-
dren’s hands because of risk of ingestion Malnutrition
• Use of occlusive clothing to prevent mosquito • Malnutrition increases susceptibility to infec-
and tick bites is effective tions; repeat or chronic infections contribute
• Remove tick from skin immediately, then to malnutrition. A vicious cycle
wash with soap and water • Malnutrition increases severity of disease and
• Keep pets tick-free risk of poor outcomes
• Immunization against disease (e.g., yellow • Malnutrition increases risk of bacterial versus
fever, typhoid, cholera, Japanese encephali- viral diarrhea
tis, meningococcus, rabies if high risk) when • Malnutrition increases risk of pneumonia
traveling to endemic area at least 2 weeks
before departure Central nervous system (CNS) diseases
• Infants have immature hypothalamic thermo-
regulatory system and lack a central “control”
ecreational Water Use
R
of temperature, making their body temperature
• Exposure to contaminated water can cause more susceptible to environmental temperature
diarrhea and other infections, e.g., swimmer’s • Infants with CNS infection affecting thermo-
ear regulatory system may present with
hypothermia
270 M. B. Laurens
Asplenia Indwelling central lines

• Example: Sickle cell anemia, congenital or • Central line-associated bloodstream infec-
surgical asplenia tions (CLABSI) are a common complication.
• Increased risk for bacteremia and meningitis Obtain culture from central line and periph-
due to encapsulated organisms like ery, then begin vancomycin + cefepime or
Streptococcus pneumoniae, H. influenzae piperacillin/tazobactam
type b (Hib), and N. meningitidis • If MRSA or methicillin-sensitive S. aureus
• Consider daily antimicrobial prophylaxis (MSSA), remove the line and continue
(especially for sickle cell disease) treatment.
• Special vaccine consideration for asplenia:
–– Pneumococcal conjugate (PCV13) and
polysaccharide (PPSV23) vaccines are VIRAL INFECTIONS
indicated
–– Following PCV13 series, PPSV23 should be Cytomegalovirus (CMV)
given at 24 months of age and 5 years later
–– Meningococcal conjugate vaccine (MCV)
should be given at 2 months of age Background
(MenACWY- CRM, e.g., Menveo). • CMV is a double-stranded DNA virus and a
Revaccinate 3 years later and then every member of the Herpesviridae family
5 years. • At least 60% of the US population has been
–– (MenACWY-D, e.g., Menactra) cannot be exposed to CMV
given before 2 years of age • CMV usually causes an asymptomatic infec-
tion; afterward, it remains latent throughout
Malignancy life and may reactivate
• Fever and neutropenia (absolute neutrophil
count [ANC] < 500) increase the risk of bac- Mode of transmission and period of
terial infection. Investigate with blood and communicability
urine cultures, consider chest radiograph, and • Vertical transmission
treat with antibiotic for Gram-positive and –– CMV can be maternally transmitted: (1)
Gram-negative coverage (cefepime or piper- transplacentally in utero, (2) at birth
acillin/tazobactam). Consider adding vanco- through infected maternal genital tract, and
mycin if methicillin-resistant S. aureus (3) postnatally by ingestion of CMV-
(MRSA) colonized or if skin/soft tissue infec- positive human milk or transfusion
tion or sepsis present. –– Risk decreased by the use of pasteurized
• Major infections in patients with cancer human milk or freezing human milk
include: bacteremia due to intestinal translo- • Horizontal transmission
cation, invasive fungal infections including –– Exposure to CMV can occur from almost
Candida and Aspergillus, Pneumocystis jir- all body fluids, including:
oveci pneumonia. ◦◦ Urine, saliva, and tears
◦◦ Genital secretions, blood transfusion,
Burn injury and transplanted organs
• Burn wounds are susceptible to infection with –– Toddlers infected postnatally with CMV
Gram-positive and Gram-negative bacteria, shed the virus in their urine for a mean of
yeast, and viruses (HSV, varicella-zoster 18 months (range 6–40 months)
virus [VZV]) –– Healthy adults infected with CMV will
shed the virus for up to several weeks
–– Shedding of CMV in toddlers in childcare • CMV pneumonitis in bone marrow or stem

centers can be as high as 70% cell transplant patients
• Transfusion and transplantation –– Ganciclovir plus CMV immune globulin
–– Can be eliminated by CMV-negative are used together
donors
–– Filtration to remove white blood cells
(WBCs) erpes Family Viruses (DNA Viruses)
H
–– Latent form in tissue and WBCs can be
reactivated many years later • Epstein–Barr virus (EBV)
• HSV1, HSV2
Congenital CMV infection • CMV
• Microcephaly • VZV
• Periventricular calcifications (intracerebral) • Human herpesvirus type 6 (HHV-6), aka sixth
• Chorioretinitis, strabismus, microphthalmia, disease
and optic nerve atrophy • Human herpesvirus type 7 (HHV-7)
• Hypotonia, poor feeding, ventriculomegaly, • HHV-6 and HHV-7 can both cause exanthema
cerebellar hypoplasia subitum, aka roseola
• Intrauterine growth restriction • Human herpesvirus type 8 (HHV-8, aka
• Prematurity Kaposi sarcoma-associated herpesvirus)
• Jaundice
• Hepatosplenomegaly Epstein–Barr Virus (EBV)
• Thrombocytopenia; petechiae and purpura
• Later in childhood 7–15% will develop pro- Background
gressive sensorineural hearing loss • EBV or human herpesvirus-4 is a gammaher-
• Developmental delays pesvirus that infects more than 95% of the
world’s population
Diagnosis • Mode of transmission primarily by oral con-
• Perinatally or postnatally: tact with saliva
–– Confirmed by detection of the virus in –– EBV is shed in saliva at high concentra-
urine, blood, saliva or CSF by culture or tions for more than 6 months following
polymerase chain reaction (PCR) acute infection and intermittently at lower
–– Congenital CMV: If diagnosed in first concentrations for life
3 weeks of life –– Young children directly or through han-
• Immunocompromised host: dling toys
–– Test for pp65 antigen (CMV antigenemia –– Adolescents due to close contact such as
assay) or quantitative DNA in blood or kissing
plasma
• Congenital CMV • EBV infection in healthy person; infectious
–– Treatment modestly improves hearing and mononucleosis (EBV is the most common
neurodevelopmental outcomes for infants cause)
–– CNS disease is treated with oral valganci- –– Fever
clovir (or IV ganciclovir) for 6 months –– Exudative pharyngitis (similar to strepto-
• CMV retinitis in HIV coccal pharyngitis but more painful)
–– Ganciclovir and valganciclovir are indi- –– Cervical lymphadenopathy, commonly
cated for induction and maintenance anterior, and posterior cervical lymph node
therapy (may compromise the airway)
272 M. B. Laurens
–– Splenomegaly (90%); 2–3 cm below the • Decrease immunosuppressive therapy in

left costal margin is typical transplant patients if possible
–– Hepatomegaly (10%) • Short courses of corticosteroids for fewer
–– Fatigue and malaise than 2 weeks can be given in the following
–– Rash cases:
–– Typically a benign, self-limited illness in –– Tonsillar inflammation with impending
healthy persons, but can cause fatal dis- upper airway obstruction
seminated infection even in healthy hosts –– Massive splenomegaly
• EBV infection in immunocompromised per- –– Myocarditis
sons (transplant, HIV) –– Hemolytic anemia
–– Fatal disseminated infection –– Hemophagocytic lymphohistiocytosis
–– Nonmalignant EBV-associated prolifera- (HLH)
tions, e.g., virus-associated hemophago-
cytic syndrome Complications
–– Post-transplant lymphoproliferative • Splenomegaly:
disorders –– Avoid strenuous activity and contact sports
–– X-linked lymphoproliferative syndrome for 21 days after onset, then limited non-
–– Nasopharyngeal carcinoma, Burkitt lym- contact aerobic activity if no overt
phoma, Hodgkin disease, non-Hodgkin splenomegaly
lymphoma, gastric carcinoma – – Contact sports allowed 4–6 weeks after
onset if no splenomegaly
Diagnosis –– Fatigue may persist for 3–6 months or
• Heterophile antibody test (monospot) longer
–– Not recommended for children younger
than 5 years of age as the result is not spe-
cific for acute mononucleosis Herpes Simplex Virus 1 and 2 (HSV1
–– Helpful for older children and adolescents and HSV2)
with mono signs and symptoms
• EBV viral capsid antigen (VCA) immuno- • Characterized by neurovirulence, latency,
globulin (Ig) M and IgG serology to distin- and reactivation in the area supplied by the
guish acute from past infection ganglia in which latency was established
–– No previous infection: Negative VCA IgG, • Reactivation induced by various stimuli (e.g.,
negative VCA IgM fever, trauma, emotional stress, sunlight, and
–– Acute infection: Positive VCA IgG, posi- menstruation)
tive VCA IgM • Spread by direct contact with lesions or infec-
–– Recent infection: Positive VCA IgG, +/− tive secretions
VCA IgM, positive early antigen
– – Past infection: Positive IgG, negative Epidemiology
VCA IgM, negative early antigen, posi- • Neonatal:
tive nuclear antigen –– Exposure during passage through birth
canal or ascending infection through rup-
Management tured or apparently intact membranes
• Ampicillin or amoxicillin may cause morbil-
liform rash
–– Risk greatest with maternal primary infec- –– Aseptic meningitis is usually mild and
tion near time of delivery (25–60%) versus associated with HSV2
2% risk if recurrent maternal infection
–– Most neonatal HSV cases born to mothers
with no HSV symptoms Herpetic Whitlow (Fig. 9.1)
• Children and adolescents:
–– Shed virus for > 1 week with primary geni- • Due to autoinoculation of HSV
tal infection (high viral concentration) • Vesiculoulcerative lesions affect the pulp of
–– Shed virus for 3–4 days with recurrent the distal phalanx of the finger associated
infection with deep-seated swelling and erythema
–– Reactivation without symptoms is common • Oral antiviral medications are optional and
–– Incubation period is 2 days–2 weeks are used in extensive disease
Clinical manifestations
• Neonatal (3 forms that may overlap): Herpes Gladiatorum (Fig. 9.2)
–– 25%: Disseminated disease affecting
• Herpes gladiatorum occurs in contact sports,
mostly liver, lungs, and CNS; “sepsis”
e.g., wrestling and boxing
clinical picture
–– 30%: CNS disease “meningoencephalitis”
–– 45%: Skin, eye, and mouth (SEM) disease
• Children and adolescents:
–– Most primary HSV is asymptomatic; reac-
tivation is also mostly asymptomatic
–– Gingivostomatitis is the most common
clinical manifestation; usually HSV1,
associated with fever, irritability, subman-
dibular lymphadenopathy and ulcerative
gums and buccal mucosa. May recur as
“fever blister” or “cold sore”
–– Genital herpes: Genital vesicles or ulcers
of genitalia and/or perineum, HSV1 or
HSV2. Immunocompromised may have
more recurrence
–– Eczema herpeticum occurs when patients
with atopic dermatitis are infected with
HSV, having ulcerative and/or vesicular
areas on top of eczematous lesions
–– Encephalitis results from primary or recur-
rent HSV, with fever, altered mental status,
seizures. Magnetic resonance imaging
(MRI) may show temporal lobe abnormali-
ties. CSF may show increased red blood
cells, but not if early in disease course Fig. 9.1 Herpetic whitlow: Herpetic Whitlow infection in a
2-year-old with vesicular lesions, ulcer, and surrounding ery-
thema involving the base of the thumb
274 M. B. Laurens
• Mucocutaneous, healthy host: May benefit

from therapy, oral acyclovir for 5–7 days
• CNS encephalitis: IV acyclovir for 21 days
Varicella-Zoster Virus (VZV):

Chickenpox and Shingles
Background and epidemiology
• VZV is herpesvirus family member
• Incubation period is 2 weeks
• Contagious 1–2 days before rash until all
lesions are crusted over
Fig. 9.2 Herpes gladiatorum: 16-year-old boy wrestling
• Spreading via airborne or direct contact with
player presents with painful blisters in the left ear mucosa of upper respiratory tract or conjunc-
tiva, and transplacental passage
• Most commonly affects exposed areas, e.g., • VZV is the cause of varicella (chickenpox)
face and upper extremities and herpes zoster (shingles)
• Patients should avoid contact sports during • Varicella is more contagious than zoster
outbreaks until the culture or PCR results are • Immunity to varicella is lifelong; reactivation
negative as zoster infection is possible
• Suppressive therapy is likely to be effective, • Immunocompromised at higher risk for
but data about such therapy are insufficient severe disease and disseminated infection

• Antivirals: Acyclovir, valacyclovir,
famciclovir Varicella (Chickenpox)
• Neonatal: IV acyclovir for 14 days (SEM dis- • The prodrome: low-grade fevers, headaches,
ease) or 21 days (disseminated disease or and malaise
CNS disease); begin therapy before test • Skin lesions initially appear on the face and
results return trunk
–– All infants with any type of HSV should • Lesions start as red macules and pass through
have ophthalmologic assessment stages of papules, vesicles with central umbili-
–– Repeat lumbar puncture near end of ther- cation, pustules, and then crust over
apy for HSV CNS disease and continue • The vesicle on the erythematous base of a
treatment if positive lesion leads to its description as a “pearl” or
–– Oral acyclovir suppressive therapy indi- “dewdrop on a rose petal”
cated for 6 months • Lesions predominate in central skin areas and
• Genital, primary: Oral acyclovir for 7–10 days proximal upper extremities with relative spar-
• Genital, recurrent: Same as primary; can be ing of distal and lower extremities
used routinely or at start of an episode • Chickenpox generally is a benign self-limited
• Mucocutaneous, immunocompromised: IV illness, and is more severe in adults, adoles-
acyclovir cents, and infants compared to older children
• Complications include bacterial superinfec- fever, avoid salicylates due to risk of Reye’s
tion, especially with Streptococcus pyogenes, syndrome
which can progress to cellulitis, myositis, and • Immunocompromised host: IV acyclovir
sepsis within 24 h of rash onset
• Pneumonia (major cause of morbidity and • Unvaccinated > 12 years old, chronic
mortality), hepatitis, and thrombocytopenia skin or lung disorders: Acyclovir or
are also possible valacyclovir
• Immunocompromised patients may experi-
ence visceral dissemination, encephalitis, Prevention in immunocompromised exposure
hepatitis • VariZIG (varicella-zoster immune globulin)
• Neonates whose mothers develop varicella or IVIG within 4 days (ideal) and up to
5 days to 2 weeks before delivery have 10 days post- exposure. Isolate for 28 days
increased risk of death due to diminished after exposure
maternal antibodies • Alternative is oral acyclovir or valacyclovir
starting 7 days after exposure. Isolate for
Herpes zoster (shingles) 21 days after exposure
• Latency establishes in sensory ganglia
infected during primary VZV or vaccination General prevention
• Shingles classically is a unilateral rash consist- • Children can return to school if all lesions are
ing of grouped vesicles on an erythematous crusted
base, covering 1–3 adjacent dermatomes, often • Airborne isolation for hospitalized patients
accompanied by pain and pruritus (Fig. 9.3) with varicella
• Postherpetic neuralgia, pain after rash • Cover skin lesions for patients with herpes
resolves, is uncommon in pediatrics zoster
• Immunize all persons who lack evidence of
Treatment of VZV immunity
• Healthy host: Keep fingernails short, topical • Immunize exposed, unvaccinated persons
calamine for itching, acetaminophen for from 3 to 5 days post-exposure
a b
Fig. 9.3 (a) 2-year-old girl with painful herpes zoster rash (shingles). (b) 4-year-old boy with herpes zoster (shingles)
276 M. B. Laurens
• Discharge or isolate exposed patients without • 10 to 15% of children with primary HHV-6
evidence of immunity will have febrile seizures
• VariZIG given to the baby born to mother • Primary infection establishes latency that
who develops illness from 5 days before until may reactivate (all herpes viruses)
2 days after birth • Immunocompromised may develop bone
• IV acyclovir is indicated for varicella infec- marrow suppression, graft rejection, pneumo-
tion in infants born to mothers who experi- nia, encephalitis, hepatitis
ence chickenpox from 5 days before until • Incubation is 9–10 days
2 days after delivery
Management
• Mainly supportive for healthy host
Human Herpesvirus Type 6 (HHV-6) • For immunocompromised, may consider gan-
ciclovir, valganciclovir, or foscarnet
I ncluding Roseola Infantum (Exanthem
Subitum) Human herpesvirus-7 (HHV-7)
• Childhood febrile illness, also causes exan-
Background them subitum (roseola)
• Commonly affects children ages 6–18 months • Most infections are asymptomatic
old • Like HHV-6, establishes latency that may
reactivate
Clinical presentation (Fig. 9.4) • 85% of healthy adults have evidence of past
• Typically, a nonspecific febrile illness with- infection
out rash
• Very high fever for 3–7 days, followed by Human herpesvirus-8 (HHV-8)
maculopapular rash in 20% after fever • Kaposi sarcoma
resolves; rash can last hours to days • A trigger for hemophagocytic lymphohistio-
• They may have lymphadenopathy, vomiting, cytosis (HLH)
diarrhea, febrile seizure, or respiratory • Multicentric Castleman disease
symptoms
Other DNA Viruses
• Parvovirus B19
• Adenovirus
Parvovirus B19
Erythema Infectiosum/Fifth Disease
Background
• Incubation period 4–14 days
• Mode of transmission: Respiratory
secretions
• Erythema infectiosum
Fig. 9.4 Roseola infantum: 9-month-old boy afebrile pres-
ents with small, pale pink papules and blanchable, maculo- –– Mild constitutional symptoms, e.g., fever,
papular exanthem, had high fever for 3 days before the rash malaise, myalgia, and headache
a b
Fig. 9.5 (a) Erythema infectiosum: Erythematous maculopapular rash on the arm, which fades into a classic lacelike reticu-
lar pattern as confluent areas clear. (b) Classic slapped-cheek appearance of fifth disease
–– Bright red facial rash (slapped cheek Remember

appearance [Fig. 9.5]) • Rash is not infectious, and children can go to
–– Circumoral pallor school without restrictions
–– Lacy maculopapular rash lasting for
2–4 days begins on the trunk and moves
to extremities (Fig. 9.5) Adenovirus
–– Rash may be pruritic, does not desquamate,
and may recur with bathing or exercise Background
–– Arthritis or arthralgia may occur • Mode of transmission:
• Mild respiratory illness without rash –– Person to person through contact with con-
• Purpuric rash in a gloves and socks junctival and respiratory secretions
distribution –– Fecal–oral transmission and via fomites
• Polyarthropathy syndrome (mostly adults) • Outbreaks usually are concentrated in winter,
• Chronic erythroid hypoplasia and severe ane- spring, and early summer; otherwise all year
mia (HIV, immunodeficient) round
• Aplastic crisis for 7–10 days • Persist in environment and resist disinfectants
–– Occurs in persons with hemolytic disease • Incubation period:
such as sickle cell anemia, spherocytosis, –– Respiratory infections from 2 to 14 days
and thalassemia –– GI disease from 3 to 10 days
–– Transient low to zero reticulocytes,
leukopenia
• Upper respiratory tract infection:
• Hepatitis and myocarditis (rare)
–– Nonspecific febrile illness
• Hydrops fetalis
–– Otitis media
–– 2 to 6% risk of fetal death if occurs during
–– Pharyngitis
pregnancy; increased risk earlier in
–– Exudative tonsillitis
pregnancy
–– Pneumonia
• Can be asymptomatic or subclinical
278 M. B. Laurens
• Follicular conjunctivitis (clinically similar to ◦◦ Point mutations causing minor antigen

enterovirus conjunctivitis) changes, leads to new influenza virus
• Gastroenteritis strains that cause seasonal epidemics in
• Hemorrhagic cystitis winter
• Pharyngoconjunctival fever: ◦◦ Reason for constant reformulation of
–– Fever, tonsillitis (sometimes suppurative) influenza vaccine to include new virus
–– Follicular conjunctivitis, coryza, and diarrhea strains
–– Cervical and preauricular lymphadenopa- –– Occasional antigenic shift:
thy is common ◦◦ Mutations causing major antigen
–– Generalized rash in association with fever, changes, leads to new influenza virus
conjunctivitis, and pharyngitis can be mis- subtypes that contain a new hemaggluti-
taken for Kawasaki disease nin (HA) or neuraminidase (NA), caus-
ing pandemics
Laboratory ◦◦ Most recent pandemic: 2009–2010
• PCR (preferred), antigen detection, and viral caused by influenza A (H1N1)
culture • Mode of transmission
• Persistent and intermittent shedding compli- –– Large-particle respiratory droplet between
cates diagnostics individuals (cough, sneeze)
–– Contact with contaminated surfaces; fin-
Management gers then touch face
• Supportive treatment in healthy host –– Incubation period is 1–4 days
• Consider cidofovir in immunocompromised • Most outbreaks occur in schools
with severe disease • Hospitalization rates are highest in children
< 2 years and elderly > 65 years
Respiratory viruses Clinical presentation
• Fever, malaise, myalgia, headache, nonpro-
• Influenza
ductive cough, sore throat, and rhinitis
• Parainfluenza
• Children may also develop croup or
• Respiratory syncytial virus
bronchiolitis
• Human metapneumovirus
• Younger children may have febrile seizures
• Rhinovirus
or sepsis-like symptoms
• Coronavirus
• Uncomplicated influenza disease typically
resolves within 3–7 days
Influenza Virus Complications
• Primary viral pneumonia
• Secondary bacterial infections such as pneu-
• Influenza is an orthomyxovirus
monia (S. aureus and S. pneumoniae)
• Types: A, B, and C. Types A and B are respon-
• Sinusitis and otitis media
sible for epidemic disease in humans
• Encephalitis
–– Influenza A viruses found in humans are
• Underlying medical conditions such as
H1N1 and H3N2
asthma, diabetes, sickle cell, immunosup-
–– Some strains are more virulent, causing
pression, neurologic disorders, or congenital
more severe disease than others
–– Frequent antigenic change, or antigenic drift:
heart disease increase risk for complications, for all when seasonal vaccine does not match
including hospitalization circulating strains
• Children who have influenza and are at high
Diagnosis risk for complications, regardless of the
• Reverse transcription-PCR and multiplex severity of their illness
PCR (testing for multiple respiratory viruses • Healthy children who have moderate-to-
at once) severe illness
• Rapid antigen-detection tests, • Three antivirals used in pediatrics:
immunofluorescence –– Oseltamivir is administered orally,
• Nasopharyngeal (NP) swab specimens have approved for > 2 weeks old; most common
highest yield adverse effects are nausea and vomiting,
• For hospitalized patients with lower respira- although neuropsychiatric events have
tory tract disease, obtain endotracheal or been reported
bronchoalveolar lavage (BAL) specimen even –– Zanamivir is inhaled, approved for treat-
if NP negative ment (age > 7) and prophylaxis (age > 5)
–– Baloxavir in children ≥ 12 years adminis-
AAP immunization guidelines tered as a single oral dose
• Annual vaccination of all children ages • Adamantanes (amantadine and rimantadine)
6 months through 18 years before the start of no longer recommended due to resistance
influenza season
• Regardless of seasonal epidemiology, chil-
dren 6 months through 8 years of age who Avian Influenza H5N1
previously have not been immunized
against influenza require two doses of triva- Background
lent or quadrivalent inactivated influenza • Reported cases were in south Asia, Iraq,
vaccine or live-attenuated influenza vac- Turkey, and Egypt
cine (LAIV) administered at least 4 weeks • Highly pathogenic strain in birds and poultry
apart to produce a satisfactory antibody • Not a human strain
response
• Children > 9 years and those who have Mode of transmission
received two doses in a previous year receive • Humans who have close contact with infected
a single dose annually birds or poultry
• Special emphasis for those with underlying • Visiting market selling live infected birds
medical conditions, including asthma, hemo-
dynamically significant cardiac disease, HIV, Clinical presentation
persons on aspirin therapy, sickle cell, diabe- • Severe lower respiratory disease in infected
tes, renal disease, pregnancy persons
• Egg allergy is not a contraindication to influ-
Prevention
enza vaccine! (but was in the past….)
• H5N1-specific vaccine (developed and
Treatment approved)
• Prophylaxis with oseltamivir or zanamivir • Avoid visiting markets where live birds are
can be given at the same time as immuniza- sold
tion and should be considered for immuno- • Thorough cooking inactivates the virus, but
suppressed, unimmunized, close contacts of avoidance of poultry if there a concern is
persons at high risk for complications, and more appropriate
280 M. B. Laurens
Parainfluenza Virus (PV) –– Reduces risk of lower tract disease in high-

risk children
Background and epidemiology –– Administered every 30 days during RSV
• Parainfluenza viruses are paramyxoviruses season (max 5 doses/season)
distinct from the influenza family –– Considered for first 1–2 years of life
• Previous infection does not confer immunity, –– Indicated for:
so reinfection can occur 1. Preterm infants with chronic lung
• Transmitted via contact with NP secretions disease
and respiratory droplets and fomites 2. Infants with hemodynamically signifi-
• Seasonal patterns of transmission: PV1 and cant congenital heart disease
PV2 occur in fall, PV3 occurs in spring, and 3. Preterm infants < 29 weeks gestational age
PV4 occurs year-round 4. Anatomic pulmonary abnormalities or
• Children shed virus for 1 week before symp- neuromuscular disorder
toms and for 1–3 weeks after symptoms resolve 5. Profoundly immunocompromised
• Incubation period is 2–6 days children
Clinical manifestation
• May cause clinical syndrome similar to H uman Metapneumovirus
influenza
• Major cause of laryngotracheobronchitis Background and epidemiology
(croup) in children (see “Respiratory” • Humans are the only source
section) • Spread via contact with infected secretions
• Can also cause pneumonia, bronchiolitis, and • A leading cause of bronchiolitis in infants
otitis media • Overlap with RSV season (winter–spring)
• Most parainfluenza infections are self-lim-
ited, but immunocompromised can have Clinical presentation
severe pneumonia and disseminated disease • Bronchiolitis indistinguishable from RSV
bronchiolitis
Treatment • Can also cause pneumonia, croup, upper
• Supportive care, as most infection is respiratory infection
self-limited • Secondary bacterial infection with S. pneu-
• Corticosteroids lessen severity, complica- moniae can occur
tions, and need for hospitalization • Severe disease in immunosuppressed and his-
• Nebulized racemic epinephrine for severe tory of preterm delivery
croup with significant inspiratory/expiratory • Most children have one human metapneumo-
stridor and retractions virus infection before 5 years of age
Treatment
Respiratory Syncytial Virus (RSV) • Supportive
• Infection with RSV, the most common

cause of bronchiolitis (See Chap. 20 Rhinoviruses
“Pulmonology”)
Prevention • The most common cause of common cold
• Palivizumab: Humanized monoclonal immu- (25–80% of cases)
noglobulin, recombinant DNA technology • The common cold is an acute respiratory tract
infection characterized by mild coryzal symp-
toms, rhinorrhea, nasal obstruction, and faces, airborne transmission of vomitus

sneezing documented
• The most common viral trigger for asthma • Highly resistant to environmental decontami-
exacerbation nation, including alcohol hand cleansers
• About 200 antigenically distinct viruses from • Incubation period is 12–48 h
8 different genera can cause common cold • Shedding may last 4 weeks in healthy host,
(66–75%) and > 6 months in immunocompromised
• Children typically have 2 episodes/year;
adults have 1 episode/year Clinical presentation
• Abrupt onset of nausea and vomiting (pro-
Clinical features fuse, nonbloody, nonbilious) more common
• Pharyngitis, nasal congestion, and discharge in adults
that goes from clear to mucopurulent • Watery diarrhea (non-bloody) may be the
• Malaise, headache, myalgia, cough, fever only symptom in children
• Symptoms peak at 3–4 days and last 7 days • Abdominal cramps
• Can cause otitis media, bronchiolitis, and • Headaches
pneumonia • Low-grade fever is common
• Myalgias and malaise
Testing • Chronic gastroenteritis in immunocompro-
• Not useful clinically mised
• PCR preferred, usually paired with enterovi- • Symptoms last 24–48 h, longer in children,
rus PCR due to genetically conserved regions immunocompromised, and elderly
GI Viral Infection

Rotavirus
• Norovirus (Norwalk virus) and Sapovirus
• Rotavirus Background and epidemiology
• Causes severe acute gastroenteritis
• Shed in stool days before and after clinical
Norovirus and Sapovirus illness
• Transmitted fecal–oral, possibly respiratory
• Late winter to early spring transmission
• Norovirus, formerly referred to as Norwalk
• Stable in environment for weeks to months
virus, is the most common cause of epidemic
• Rotavirus was most common viral cause of
nonbacterial gastroenteritis in the world
acute gastroenteritis until vaccine introduc-
• Norovirus is the leading cause of viral gastro-
tion that reduced hospitalizations by 75% for
enteritis cases in the USA, after rotavirus vac-
children < 5 years
cine introduction
• Norovirus causes death in young children and Clinical presentation
the elderly • Acute onset vomiting, then 24 h later severe
• Sapoviruses also cause outbreaks watery diarrhea
• Outbreaks of both occur in crowded areas • Up to 33% have high fever
(schools, long-term care facilities, cruise • First infection is more severe
ships) • Causes dehydration, electrolyte imbalance,
• Transmission is fecal–oral or vomitus–oral, and metabolic acidosis
contaminated food/water, contaminated sur- • Symptoms last 3–7 days
282 M. B. Laurens
• Immunocompromised may have severe, pro- –– Severe complications: Seizure, hemipare-

longed, and fatal symptoms sis, hearing loss, and mental deterioration
–– No signs of toxicity (hypotension, hypo-
Diagnosis perfusion) as in bacterial meningitis
• Antigen assay testing (enzyme immunoassay, –– Best diagnostic test: CSF enterovirus PCR
chromatographic immunoassay, latex • Herpangina
agglutination) –– Caused by many enteroviruses, including
coxsackievirus type A
RNA Viruses –– Sudden onset of high fever in children
3–10 years of age, and can be associated
• Enterovirus
with vomiting, malaise, myalgia, and
• HIV
backache
• Measles
–– Poor intake, drooling, sore throat, dyspha-
• Mumps
gia, and dehydration may occur
• Rubella
–– Oral lesions:
• Rabies
◦◦ One or more small tender papular pinpoint
• Arboviruses
vesicular lesions, on erythematous base on
anterior pillars of the fauces, soft palate,
Enteroviruses (Non-polio Viruses uvula, tonsils, and tongue, then ulcerate in
3–4 days
and Poliomyelitis) • Hand, foot, and mouth disease (Fig. 9.6)
Non-polio Viruses (Echovirus, –– Mostly caused by coxsackie A16 and
Coxsackievirus, and Numbered enterovirus 71
Enteroviruses) –– Fever (may be present)
–– Oral vesicles and ulcers on buccal mucosa
Background and epidemiology and tongue
• More common in the summer and fall –– Painful erythematous vesicles on hands and
• Humans are the only known reservoir for feet; it may affect the groin and buttocks
human enteroviruses –– Usually last for 7–10 days
• Enteroviruses transmitted by the fecal–oral –– Most common complication is dehydration
route and respiratory route due to odynophagia
• Survive in environment for long periods • Acute hemorrhagic conjunctivitis (similar to
• Outbreaks can occur adenovirus conjunctivitis)
• Most severe disease in infants and young –– Subconjunctival hemorrhage
children –– Swelling, redness, and tearing of the eye
• Viral shedding in stool (weeks to months) and –– Resolves spontaneously within 7 days
respiratory secretions (1–3 weeks) • Myocarditis/pericarditis
–– Commonly caused by coxsackievirus B or
Clinical manifestations echovirus
• Meningitis/encephalitis –– Common symptoms: Shortness of breath,
–– Enterovirus is the most common cause of chest pain, fever, and weakness
meningitis in pediatrics (bacterial or viral) • Congenital and neonatal infection
–– Meningitis commonly caused by echovirus –– Sepsis-like syndrome associated with
–– Common in older children maternal enterovirus infection and lack of
–– Fever, headache, photophobia, and nuchal maternal immunity
rigidity, CSF pleocytosis
a b
c d
Fig. 9.6 Hand, foot, and mouth disease. (a) Tender macules in the hand. (b) Tender macules and vesicles in both feet. (c)
Multiple painful vesicles on the hard palate. (d) Erythematous macules all over the body and feet in an 18-month-old who
has fever and oral ulcers
–– Can range from mild febrile infection to • Most respiratory panels with multiplex PCR
encephalitis and negative bacterial culture do not distinguish enterovirus from rhinovi-
–– Can cause hepatic necrosis rus due to genetic similarity and testing for a
shared, conserved region in genome
Diagnosis • Enterovirus 71 often has negative PCR
• PCR from rectal swab, stool, throat, naso- testing
pharynx, conjunctiva, trachea, blood, urine,
tissue biopsy, and CSF
284 M. B. Laurens
Treatment uman Immunodeficiency Virus

H
• Supportive, and IVIG can be considered for (HIV)
immunocompromised to reduce illness and
duration of shedding Background
• HIV is RNA virus
• Highest infectivity due to the very high
Poliomyelitis (3–4 weeks) initial viremia
• Nearly all patients seroconvert within
6 months of acquiring the infection
• Humans are the only reservoirs
• Three serotypes: Types 1, 2, and 3; type 2 Mode of transmission
eradicated globally; type 3 not seen since • Transmitted by two principal modes in the
2012; only type 1 is currently circulating pediatric age group:
• Paralytic disease caused by wild type or live, • Mother-to-child
oral vaccine virus –– Transplacental transfer
• Stable in liquid environment (pools, ponds, etc.) –– Exposure to maternal blood, amniotic fluid,
• After illness, virus persists in throat and cervicovaginal secretions during
(1–2 weeks) and GI tract (3–6 weeks) delivery
• Incubation period 3–6 days; paralysis occurs –– Postpartum through breastfeeding
1–3 weeks after exposure • Behavioral (risk behavior in adolescent
either unprotected sex or injection drugs)
• Other transmission modes include needle-
• Asymptomatic infection in 70%
stick injury, mucous membrane exposure,
• Fever and sore throat in 25%
and transfusion
• Aseptic meningitis in 1–5%
• Flaccid paralysis in a descending manner Clinical presentation
without reflexes in < 1% • During the “window” period:
–– Follows febrile illness –– Infected person has a negative HIV anti-
–– Symmetric paralysis affecting proximal body test result, but HIV RNA testing
muscles results are usually positive
–– Cranial nerve and diaphragm/intercostal • Acute retroviral syndrome, characterized by:
muscle involvement may affect respiration –– Fever, lymphadenopathy, rash, myalgia,
–– 33% recover arthralgia, headache, diarrhea, oral ulcers,
• Affects anterior horn cells in the spinal cord leukopenia, thrombocytopenia, and
transaminitis
Diagnosis
• Red flags for HIV infection
• Cell culture of pharynx, stool, and CSF
–– Thrush in apparently healthy child or
obtained as early as possible
adolescent
Treatment –– Invasive candidal infections
• Supportive –– Recurrent severe infections
–– Lymphadenopathy and/or hepatospleno-
megaly
–– Failure to thrive
• Parotid enlargement • For confirmatory serology testing:

• Opportunistic infections –– Differential antibody testing to HIV-1 and
–– Pneumocystis jiroveci pneumonia HIV-2
–– Mycobacterium avium complex –– HIV-1 Western blot and HIV-1 indirect
–– Cytomegalovirus immunofluorescence assay
–– Toxoplasma gondii
–– Human viscerotropic leishmaniasis Evaluation of HIV positive children
• CD4 percentage and absolute cell counts
Diagnosis: Perinatal and postnatal infection • Plasma HIV RNA concentration (viral load)
• Preferred overall test in infants and children • HIV genotype to assess for baseline resis-
< 18 months is HIV DNA PCR; highly spe- tance and mutations
cific by 2 weeks of age • Complete blood count with differential count
–– 55% sensitivity at birth that increases to • Serum chemistries with liver and renal func-
100% by age 3 months tion tests
• Preferred test for HIV-1 infection is HIV • Lipid profile and urinalysis
RNA PCR because of greater clinical • For children younger than 5 years of age,
experience CD4 percentage is the preferred test for mon-
• Some use both to obtain viral load and itoring immune status
confirmation • Screening for hepatitis B, hepatitis C, and
• Maternal antibody transfer can complicate tuberculosis is recommended for all HIV pos-
diagnostics itive patients
• In HIV exposed, test at delivery, 2–3 weeks,
1–2 months, and 4–6 months Treatment of HIV
• Presumed negative in children < 18 months • Triple-drug combination antiretroviral ther-
if: Two negative HIV DNA or RNA tests from apy effectively controls HIV infection
separate specimens at > 2 weeks of age, one
negative HIV DNA or RNA test from Prevention
> 8 weeks of age, or one negative HIV anti- • Breastfeeding is contraindicated in HIV posi-
body test at > 6 months of age and no clinical tive mothers
or laboratory evidence of infection • All exposed infants should receive 6 weeks of
• Definitive negative in non-breastfed zidovudine
< 12 months: At least 2 negative HIV DNA • Condoms and abstinence are the best forms
or RNA virologic tests from separate speci- of preventing sexual transmission of AIDS
mens at > 1 month and > 4 months, at least 2 • Cesarean delivery and treatment of HIV-
negative HIV antibody tests from separate positive mothers (especially with high viral
specimens at > 6 months and no clinical or load) decreases the risk of transmission of
laboratory evidence of infection HIV to their infants
• Immunization of infants and children
Diagnosis: Adult and adolescent infection –– Immunization schedule for HIV-exposed
• Conduct initial serology, followed by confir- children is the same as for their healthy
matory serology testing peers, with only a few exceptions:
• For initial serology testing: ◦◦ Patients who have severely symptomatic
–– Antibodies to HIV-1/HIV-2 and HIV-1 p24 illness
antigen (fourth generation) ◦◦ Patient with CD4 percentage of less than
–– Antibodies to either HIV-1 and HIV-2 15% or CD4 counts of less than 200
(third generation) cells/mm3 should not receive MMR, var-
icella vaccines, or other live vaccines
286 M. B. Laurens
• Annual influenza immunization is recom- • HIV on antiretroviral therapy and docu-

mended for all children older than age mented measles vaccination × 2: Treat as
6 months, but only the killed vaccine immune
• Vaccinate all health-care personnel
Measles Virus
Mumps
Background
• Mode of transmission: Respiratory droplets Background
(airborne) • An acute, self-limited, systemic viral illness
• Infectious for 3–4 days before the onset of characterized by the swelling of one or more
morbilliform rash and 4 days after the of the salivary glands, typically the parotid
exanthem glands
Diagnosis Mode of transmission

• PCR testing, IgM detection, 4-fold rise in IgG • Contact to respiratory secretions
serology, cell culture • Incubation period is 16–18 days
• IgM detection is preferred test
Clinical presentation • Symptoms in the patient’s history consist
• High fever plus coryza, cough, conjunctivitis mostly of fever, headache, and malaise
• Rash develops next: Erythematous, morbilli- • Within 24 h, patients may report ear pain
form, maculopapular rash spread from face localized near the lobe of the ear and aggra-
downward and disappears the same way vated by a chewing movement of the jaw
• Koplik spots (white spots on oral mucosa) • Unilateral or bilateral parotid swelling
during prodrome (Fig. 9.7)
• Complications in young children and immu- • Orchitis may occur after puberty; rarely
nocompromised include otitis media, bron- causes sterility
chopneumonia, croup, diarrhea, and death
• Death is also more common with severe Complications
malnutrition • Rare: Arthritis, thyroiditis, glomerulonephri-
• Severe complication: Acute encephalitis with tis, myocarditis, transverse myelitis, enceph-
permanent brain damage alitis, oophoritis, permanent hearing
impairment
Control and prevention
• Vaccinate non-immunes within 72 h of Diagnosis (Table 9.1)
exposure • PCR from buccal swabs, throat washings,
• Immune globulin within 6 days of exposure saliva, or CSF
for non-immunes if vaccination not possible, • Viral cell culture
including pregnant women, severe primary • Serology
immunodeficiency, bone marrow or solid
organ transplant recipient, acute lymphoblastic Treatment
leukemia, HIV AIDS with severe immunosup- • Supportive care only
pression, and infants whose mothers received • School exclusion for 5 days from onset of
immunomodulatory drugs during pregnancy parotid gland swelling
• The USA has not experienced rubella trans-

mission since 2004; imported cases occur
• The Americas have not experienced rubella
transmission since 2009
• Incubation period: 16–18 days
• Congenital rubella syndrome
–– Constellation of congenital anomalies
◦◦ Ophthalmologic (cataracts, microph-
thalmos, congenital glaucoma)
◦◦ Cardiac (patent ductus arteriosus,
peripheral pulmonary artery stenosis)
◦◦ Auditory (hearing impairment)
Fig. 9.7 Child with unilateral parotitis ◦◦ Neurologic (meningoencephalitis,
microcephaly, mental retardation,
autism)
Table 9.1 Differences between viral and bacterial parotitis –– Neonates will have growth restriction,
Viral parotitis (mumps) Bacterial parotitis interstitial pneumonitis, hepatosplenomeg-
Well-appearing Toxic-appearing or ill-looking aly, thrombocytopenia, and dermal eryth-
No fever or low-grade High fever ropoiesis that manifests as “blueberry
fever
Mild tenderness Moderate or severe tenderness
muffin” rash
Normal labs, positive Leukocytosis, shift to the left, –– Neonates may also have metaphyseal
mumps IgM high CRP lucencies (also seen in vitamin D intoxica-
IgM Immunoglobulin M, CRP C-reactive protein tion/hypercalcemia, rickets, scurvy, arse-
nic and heavy metal poisoning, leukemia,
congenital syphilis, sickle cell disease,
• Unimmunized children should stay out of
congenital hypothyroidism)
school for 26 days after onset of parotitis in
–– Increased risk of congenital defects if fetal
the last person with mumps in the affected
infection occurs early in pregnancy
school.
• Postnatal rubella
–– Subclinical or mild disease
Rubella Virus –– Erythematous maculopapular rash
–– Forchheimer spots: Rose-colored spot on
Epidemiology soft palate
• Transmitted via direct or droplet contact with –– Lymphadenopathy (posterior auricular or
respiratory secretions suboccipital nodes)
• Peak incidence from winter to spring –– Conjunctivitis
• 25 to 50% asymptomatic –– Adolescent females susceptible to transient
• Lifelong immunity arthralgia and arthritis
• Can transmit 3 days before to 7 days after –– Rare complications: Encephalitis,
rash appears thrombocytopenia
• Infants with congenital rubella may shed for • Infants with congenital rubella may shed the
1 year in nasopharyngeal secretions and urine virus from the nasal mucosa > 1 year to sus-
ceptible contact
288 M. B. Laurens
Rabies Virus Arboviruses (Arthropod-Borne Viruses)
Background • West Nile virus (WNV)

• RNA virus classified in the Rhabdoviridae • Dengue fever
family
• Usually transmitted by bats and carnivores,
e.g., raccoons, foxes, and coyotes est Nile Virus
W
• Almost never transmitted by squirrels, chip-
munks, rats, mice, rabbits, and guinea pigs Background and epidemiology
• The most common neuroinvasive arboviral
Clinical presentation disease in the USA
• Anxiety • Transmitted to humans by Culex mosquitoes
• Dysphagia • Transmission occurs from summer to fall
• Seizures • California, North and South Dakota, Nebraska
• Encephalitis and Illinois were the most common locations
• In most cases, progress to death in 2018
• Incubation 2–6 days
Treatment • Humans also infected via transfusion and
• Prompt local flushing and cleaning the wound organ transplant
with soap and water
• Passive and active immunization for: Clinical presentation
–– All persons bitten by bats, carnivores, e.g., • Most cases are asymptomatic (70–80%)
raccoon, foxes, and coyotes • May present with fever and flu-like
–– Open wound or scratch contaminated with symptoms
saliva of infected animals or human • Fever, headache, myalgia, arthralgia, vomit-
• No prophylaxis if domestic dog, cat or ferret ing, diarrhea, transient rash
that can be observed for 10 days • < 1% have neuroinvasive disease: Meningitis,
• Domestic animals that may be infected should encephalitis, acute flaccid myelitis
be euthanized and tested • WNV encephalitis: Altered mental status,
• The need for tetanus and local wound care seizures, paresis, nerve palsies, or coma in
should be considered more severe cases
• Most recover completely but can take months
Passive and active immunization should be
started as soon as possible Diagnosis
• Human rabies immunoglobulin (passive) • Anti-WNV IgM in serum or CSF may take a
• Rabies vaccine (active) week to turn positive
• Both should be given together
• Human rabies immunoglobulin: As much as Treatment
possible of the dose should be infiltrated • Supportive
directly to wound, the remainder of the dose
should be given intramuscularly (IM)
• Rabies vaccine should be given IM in oppo- Dengue Fever
site arm or thigh, the first dose immediately
after exposure then repeated at days 3, 7, and Background and epidemiology
14. Immunocompromised persons get an • Arbovirus transmitted by Aedes mosquitoes
additional dose at day 28 • History of travel to endemic area
• Endemic in Asia, Africa, Latin America, and • Oncogenic strains 16 and 18 are responsible
Puerto Rico for two thirds of all cervical cancers
• Transmission has occurred in Hawaii, Florida, • Nononcogenic HPV type 6 and 11 are respon-
and Texas sible for > 90% of anogenital warts
• Incubation period is 3–14 days
Clinical features
Clinical presentation • Most infections are subclinical
• Can be asymptomatic • Skin warts are generally painless; plantar
• Febrile illness lasting 2–7 days: Pain in mus- warts can be painful
cles, joints and bones, headache; retro-orbital • Anogenital warts (condylomata acuminata)
pain, facial erythema, injected oropharynx, have cauliflower-like surface and can occur in
macular or maculopapular rash, leukopenia, groups
petechiae • Invasive cancers linked to HPV include the
• Critical phase: 24–48 h with plasma leakage following locations: Oropharynx, penis, anus,
• Convalescent phase: Improvement and cervix, vagina, and vulva
stabilization • Squamous intraepithelial lesions can be low
• Severe dengue (dengue hemorrhagic fever or or high grade due to persistent HPV
dengue shock syndrome) occurs in 5% and • Cervical intraepithelial neoplasia (CIN) is
can be deadly precancerous and linked to HPV
• Increased risk for severe dengue with subse- • Adenocarcinoma in situ is another endocervi-
quent infection cal precancer
Laboratory Immunization
• During febrile phase, diagnose with PCR for • 2 doses before 15th birthday
viral DNA or immunoassay for nonstructural • Only 9-valent vaccine available in USA since
protein 1 (NS-1) 2017
• From 3 to 5 days after onset, can test for anti-
dengue IgM
• Leukopenia, thrombocytopenia, and modest BACTERIAL PATHOGENS
elevation of liver enzymes
Gram-Positive Bacteria
Treatment
• Supportive S. aureus
Human Papillomavirus (HPV) • S. aureus is the most common cause of skin
and soft tissue infection and musculoskeletal
Background and epidemiology infection in healthy children
• Most adults will be infected at some time • Second leading cause of healthcare-associ-
• School-age children acquire nongenital hand ated bacteremia (coagulase-negative staphy-
and foot warts through minor skin trauma lococci is first)
• Genital transmission occurs skin-to-skin • Leading cause of secondary bacterial pneu-
• HPV causes most vulvar, vaginal, penile, monia in children
and anal cancers; 70% of oropharyngeal • Most common cause of healthcare-associated
cancers surgical site infections
• Rare transmission to infant during delivery • Coagulase positive
• Incubation period is months to years • Grapelike clusters (Fig. 9.8)
290 M. B. Laurens
• Children who undergo neurosurgical proce-

dures, especially shunt revisions, are at high
risk for staphylococcal infection
• Indwelling bloodstream catheters can be
associated with staphylococcal infection and
must be removed if the patient develops
symptoms or positive culture
Folliculitis/Furunculosis/
Carbunculosis (Fig. 9.9)
Background
Fig. 9.8 Staphylococci in blood culture (Gram stain, origi-
• Folliculitis: Superficial inflammation cen-
nal magnification × 1000). The bacteria are Gram-positive tered around a follicle
cocci and grow in pairs, tetrads, and clusters (arrow). • Furuncles: Bacterial folliculitis of a single
(Courtesy of M. Nawar Hakim, MD, Department of follicle that involves a deeper portion of the
Pathology, Texas Tech University Health Sciences Center, El follicle
Paso, Texas, USA)
• Carbuncle: Bacterial folliculitis that involves
the deeper portion of several contiguous
• S. aureus colonizes the nares and skin in follicles
30–50% of children • Bacterial folliculitis most often caused by S.
• Transmitted by direct contact and indirectly aureus.
from other patients in hospital settings • Hot tub folliculitis is usually caused by Gram-
• Can spray short distances into the air negative bacteria (most often P. aeruginosa;
• “Vancomycin-intermediately susceptible S. self-limited)
aureus” related to repeat vancomycin use in • Usually the child looks healthy and does not
individuals. Vancomycin-resistant S. aureus appear ill
rare • Abscess (< 5 cm) drainage alone is curative
• Incubation period can be 12 h for postopera- without antibiotics and should be performed
tive toxic shock syndrome along with a request for culture
Common staphylococcal infections Management of skin and soft tissue infections

• Bullous and crusted impetigo • Indication for antibiotics
• Skin and soft tissue or lymph node infection –– The child has high fever or other systemic
• If the organism seeds the bloodstream, dis- symptom
semination to joints, bones, kidney, liver, – – The abscess is larger than 5 cm
muscles, lungs, and heart valves may occur, –– Located in a critical location or in an area
causing substantial morbidity and potential difficult to drain
mortality –– Signs and symptoms persist following inci-
• S. aureus is the most common cause of osteo- sion and drainage
myelitis, including sickle cell disease patients • Common oral anti-staphylococcal antibiotics
(who are also at increased risk for Salmonella –– Trimethoprim–sulfamethoxazole (TMP-
osteomyelitis) SMX) effective against most MRSA
• Children with cyanotic congenital heart dis- – – Cephalexin remains a good empiric choice
ease are at high risk of staphylococcal brain for MSSA and group A Streptococcus
abscess (GAS) infections
a –– Treatment with antibiotic-based decoloni-

zation regimens (usually rifampin plus an
additional agent) in selected cases
Toxic Shock Syndrome (TSS)

Background
• Production of toxic shock syndrome toxin-1
(TSST-1)
• Can be caused by S. aureus or S. pyogenes
(aka group A Streptococcus or GAS)
b
Risk factors
• Tampon
• Surgical implants
• Invasive staphylococcal disease, including
pneumonia and skeletal infection
• Nasal packing
• Progressive skin infection in cases caused by
S. pyogenes
• Fever
• Vomiting
• Hypotension (abrupt onset)
• Hypocalcemia
Fig. 9.9 (a) Furuncle: Erythematous tender papulonodule
• Watery diarrhea
with central punctum with point of fluctuant. (b) Folliculitis:
Superficial inflammation centered around a follicle, tender to • Myalgia
touch • Strawberry tongue
• Conjunctival hyperemia
–– Clindamycin • Rash with hand and foot desquamation
–– Doxycycline (in children older than 8 years • Blood culture is usually negative if the cause
of age) is S. aureus
–– Linezolid (for resistant MRSA infections • Blood culture is usually positive if the cause
not susceptible to TMP-SMX or is S. pyogenes
clindamycin)
• Recurrent staphylococcal skin infections Treatment
recommendations • Vancomycin + clindamycin (stops toxin pro-
–– Enhanced hygiene and environmental duction) + nafcillin or oxacillin, pending cul-
cleaning ture results
–– Treatment for anyone in the family who • In cases of tampon-associated TSS, must be
has active disease removed immediately and the recommended
–– Nasal and perianal mupirocin length of therapy is 10–14 days
–– Skin decolonization (chlorhexidine and/or • IV fluids and routine management of shock;
bleach baths) consider IVIG for refractory shock
292 M. B. Laurens
• Do not treat hypocalcemia unless symptom- • A biopsy of the affected area will demon-
atic or electrocardiogram changes strate separation of the epidermis at the gran-
• Anytime there is a postsurgical toxic shock, ular layer
any device implanted during surgery must be
removed immediately Management
• Fluid rehydration is initiated with lactated
Ringer solution at 20 mL/kg initial bolus
Staphylococcal Scalded Skin • Repeat the initial bolus, as clinically indi-
Syndrome (SSSS) cated, followed by maintenance therapy
with consideration for fluid losses from
Background exfoliation of skin being similar to a burn
• SSSS (aka Ritter disease of the newborn) patient
• Ritter disease and staphylococcal epidermal • Prompt treatment with parenteral anti-staphy-
necrolysis encompass a spectrum of superfi- lococcal antibiotics is essential
cial blistering skin disorders caused by exfo-
liative toxins of some strains of S. aureus
• SSSS differs from bullous impetigo; the exfo- S. aureus Food Poisoning
liative toxins are restricted to the area of
infection in bullous impetigo, and bacteria Background
can be cultured from the blister contents • The most common cause of food poisoning in
• Exfoliative toxins cause separation of the the USA
epidermis beneath the granular cell layer. • Eating contaminated food containing pre-
Bullae and diffuse sheetlike desquamation formed enterotoxin
occurs • Usually associated with meat, baked food
• Exotoxin is a protein and is classified as either filled with cream, and mayonnaise
type A or B. Most are type A • Incubation period < 4–6 h

• Fever, malaise, and irritability • Nausea, vomiting, and abdominal cramps in
• Most of the patients do not appear severely ill few hours after exposure to contaminated
• Tenderness to palpation food
• Dehydration may be present and can be • Fever may be present
significant • Some children can have severe dehydration
• Nikolsky sign (gentle stroking of the skin
Management
causes the skin to separate at the epidermis)
• Hydration
• Bacteremia may or may not present
• No antibiotic required
Diagnosis
• Blood cultures are usually negative in chil-
dren (but positive in bullous impetigo) and is
taphylococcal, Coagulase-Negative
S
usually positive in adults Background
• A chest radiograph should be considered to • Staphylococcus epidermidis and
rule out pneumonia as the original focus of Staphylococcus saprophyticus are examples
infection of coagulase-negative staphylococci
• S. epidermidis is methicillin-resistant in most Alternative drugs

cases • Cefazolin
• S. epidermidis is the most common cause of • Clindamycin
catheter-related bacteremia • Vancomycin
• Catheter becomes contaminated when pass- • Ampicillin + sulbactam
ing through the skin
• S. epidermidis is a common contaminant in
the blood cultures Methicillin-Resistant Staphylococcus
aureus (MRSA)
Common source of infection
• Skin, mucous membrane Background
• Nosocomial infection • MRSA strains are resistant to all beta-lacta-
• IV catheter mase resistant (BLR) beta-lactam and cepha-
• Ventriculoperitoneal shunts losporin antimicrobials and other
• Prosthetic devices, e.g., heart valves, joints, and antimicrobial agents
pacemakers
• Bone marrow transplant Drug of choice in MRSA cases (oxacillin MIC, 4
• Premature infants (intravascular catheter) ≥ μg/mL)
• Vancomycin ± gentamicin or ± rifampin
Management (multidrug resistance)
• Removal of the foreign body may be neces- • For example, endocarditis, septicemia, and
sary to clear the infection CNS infection (combination therapy is
• In neonatal intensive care unit (NICU), posi- recommended)
tive culture must be initially treated if suspi- • Alternative drugs in MRSA cases (multidrug
cious of infection resistance)
• Draw two cultures from two different sites. –– Trimethoprim–sulfamethoxazole
To be considered positive, both cultures –– Linezolid
should be positive within 24 h. –– Quinupristin/dalfopristin
• Vancomycin is the drug of choice –– Daptomycin
–– Treat for 7–9 days for bacteremia
Methicillin-Sensitive S. aureus Community (not multidrug resistance)

(MSSA) • Vancomycin ± gentamicin (or ± rifampin)
for life-threatening infections, e.g.,
Background endocarditis
• Most of S. aureus strains produce beta-lacta- • Clindamycin (if strain susceptible) for pneu-
mase enzyme and are resistant to penicillin monia, septic arthritis, osteomyelitis, skin, or
and ampicillin soft tissue infection
• TMP-SMX for skin or soft tissue infections
Drug of choice • Daptomycin for vancomycin-intermediately
• Nafcillin or oxacillin (+ rifampin if indwell- susceptible S. aureus
ing foreign body)
• Treat for 3–4 days for bacteremia
294 M. B. Laurens
. pneumonia (Pneumococcal
S • Immunosuppressive medications or bone
Infection) marrow transplants also are at increased risk
• CSF leaks, e.g., neurosurgical procedures or
Background and epidemiology skull fractures
• S. pneumoniae is a Gram-positive, catalase- • Cochlear implants
negative, alpha-hemolytic bacterium • Chronic heart or lung disease
• The bacteria are Gram-positive diplococci • Diabetics
(Fig. 9.10)
• Introduction of pneumococcal conjugate Clinical manifestations
vaccines (PCV7 and PCV13) significantly • Common pneumococcal infections include:
reduce invasive pneumococcal disease in –– Acute otitis media
children –– Sinusitis
• Nasopharyngeal carriage rates are 21% for –– Pneumonia
industrialized countries to 90% in resource- –– Bacteremia (most common manifestation
limited settings of invasive pneumococcal disease)
• Transmission is person-to-person via respira- –– Meningitis (leading cause of meningitis)
tory droplets, occurring with viral upper • Pneumonia
respiratory infections –– S. pneumoniae is the most common bacte-
• More common in winter rial cause of community-acquired pneumo-
• Incubation period is 1–3 days nia in both children and adults
–– High fever and ill-appearing
Risks of invasive pneumococcal disease –– Cough and tachypnea
• The highest age-specific attack rates occur –– Respiratory distress
during the first 2 years of life –– Crackles
• Children who have sickle cell disease –– Diminished breath sounds
• Children who have asplenia –– Lobar consolidation may be noted on chest
• Congenital immune deficiencies radiography in older children
–– Know: Infants and young children may
have bronchopneumonia with a scattered
distribution of parenchymal consolidation
–– Pleural fluid may be evident in some
patients
Diagnosis
• Culture from blood or normally sterile body
fluids such as CSF, pleural, synovial, or mid-
dle ear fluid
• PCR on blood or CSF specimen
• Positive results should have antimicrobial
susceptibility testing for penicillin, cefo-
taxime or ceftriaxone, and clindamycin.
Fig. 9.10 Streptococcus pneumoniae (pneumococci) in Treatment

blood culture (Gram stain, original magnification × 1000). • Outpatient otitis media: Amoxicillin (80–
The bacteria are Gram-positive diplococci (arrows). They 90 mg/kg/day for < 6 months and
are often lancet-shaped. (Courtesy of M. Nawar Hakim, MD, 6–23 months with bilateral disease) with
Department of Pathology, Texas Tech University Health
watch and wait 48–72 h for older children
Sciences Center, El Paso, Texas, USA)
and nonsevere disease. Treat 10 days for G roup A Beta-Hemolytic

severe disease. Treat 5–7 days for > 6 years Streptococcus (GAS) Pharyngitis
for mild or moderate disease. Alternate ther-
apies include amoxicillin-clavulanate, cef- Background and epidemiology
dinir, cefpodoxime or cefuroxime or IM • Causes pharyngitis and impetigo
ceftriaxone × 3 doses. Same dosages for • Pharyngitis: Transmits via contact with
sinusitis if bacterial sinusitis diagnosed. If respiratory tract secretions of infected
penicillin allergic type I (anaphylaxis), use person
clindamycin or levofloxacin • Impetigo: Transmits via direct contact from
• Outpatient pneumonia: Amoxicillin another person
(90 mg/kg/day) • Increased risk for pharyngitis and impetigo
• Inpatient pneumonia: Parenteral ampicillin. with crowding
Alternatives: Cefotaxime and ceftriaxone • Most often in schools, childcare centers, con-
• Pneumococcal meningitis: Due to antibiotic tact sports
resistance concerns, treatment of proven or • Some are chronic pharyngeal carriers
suspected cases mandates empiric therapy • Increased risk of invasive GAS infection in
with cefotaxime or ceftriaxone plus vanco- infants and elderly
mycin while awaiting susceptibility results. • Like S. aureus, can cause TSS
Discontinue vancomycin if susceptible to • Rheumatic fever can develop in about 3% of
penicillin, cefotaxime, or ceftriaxone untreated patients with GAS pharyngitis
• Other invasive pneumococcal infections, • Incubation period for GAS pharyngitis is
inpatient: Same as for pneumococcal 2–5 days; for GAS impetigo is 7–10 days
meningitis • For TSS, can occur 14 h after inoculation of
organism (e.g., trauma)
Streptococcus pyogenes
• Group A Streptococcus (GAS) is a Gram- • Sore throat, fever, headache, and abdominal
positive bacterium that grows in chains pain the most classic presentation
(Fig. 9.11) • Nausea and vomiting may occur
• Pharyngeal erythema and palatal petechiae
(Fig. 9.12)
• Inflammation of the uvula
• Anterior cervical lymphadenopathy
• Tonsillar exudates may or may not be
present
Fig. 9.11 Streptococci in blood culture (Gram stain, origi-

nal magnification × 1000). The bacteria are Gram-positive
cocci and grow in chains (arrow). (Courtesy of M. Nawar
Hakim, MD, Department of Pathology, Texas Tech University Fig. 9.12 Streptococcal pharyngitis: Palatal petechiae,
Health Sciences Center, El Paso, Texas, USA) rapid strep was positive in this patient
296 M. B. Laurens
Diagnosis • Close contact who has a history of rheumatic

• Rapid antigen detection test is highly recom- fever
mended to decrease overuse of antibiotics • Families experiencing repeated episodes of
• Testing of asymptomatic household con- GAS pharyngitis
tacts not recommended except when con- • Eradication regimens include clindamycin,
tacts are at increased risk of developing cephalosporins, amoxicillin–clavulanate
sequelae of GAS infection, e.g., rheumatic
fever, post-streptococcal glomerulonephri-
tis, or TSS carlet Fever (Scarlatina)
S
• If rapid antigen detection test (RADT) posi-
tive, treat (specificity of 95%) Background
• If RADT is negative, do throat culture (sensi- • Syndrome characterized by exudative phar-
tivity of 65–90%) yngitis, fever, and scarlatiniform rash
• Treatment of GAS sore throat as long as • Caused by toxin-producing GAS found in
9 days after the onset of symptoms still secretions and discharge from the nose, ears,
effectively prevents rheumatic fever; initia- throat, and skin
tion of antibiotics is seldom of urgent
importance
• Fever may be present
Treatment • Patient usually appears moderately ill
• Reduces complications • On day 1 or 2, the tongue is heavily coated
• Decreases the duration of infection with a white membrane through which
• Reduces transmission to others edematous red papillae protrude (classic
• Oral penicillin VK (250–500 mg twice to appearance of white strawberry tongue)
three times a day for 10 days) is the antibi- (Fig. 9.13)
otic treatment of choice for GAS • By day 4 or 5, the white membrane sloughs
pharyngitis off, revealing a shiny red tongue with promi-
• Amoxicillin (50 mg/kg, maximum 1 g, once nent papillae (red strawberry tongue)
daily for 10 days) often is used instead of oral • Red, edematous, exudative tonsillitis
penicillin because of its more palatable liquid
formulation
• Cephalosporins or macrolides may be used
as first-line therapy in patients allergic to
beta-lactam antibiotics but otherwise are
not recommended as first-line therapy
• IM benzathine penicillin G 600,000 U for
children who weigh < 27 kg and 1.2 million
U for heavier children as a single dose (if
adherence is a problem but is painful)
• Know: Treatment is indicated if a GAS car-
rier develops an acute illness consistent with
GAS pharyngitis
Treatment to eradicate GAS carriage

indications Fig. 9.13 Strawberry tongue with white coat in a child with
• History of acute rheumatic fever scarlet fever
• Diffuse, erythematous, blanching, fine papu- • Low-grade fever

lar rash that resembles sandpaper on palpa- • Thick purulent nasal discharge
tion (Fig. 9.14) • Poor feeding
• The rash is prominent especially in the flexor • Anterior cervical lymphadenopathy
skin creases of the antecubital fossa and axil- • Some patients may be toxic with high fever,
lae (Pastia lines, which are pathognomonic malaise, headache, and severe pain upon
for scarlet fever) swallowing
• Circumoral pallor
• Desquamation after the rash starts to fade
(usually the rash lasts about 1 week) Impetigo
• Throat culture or rapid streptococcal test • GAS impetigo is a superficial bacterial skin
• Anti-deoxyribonuclease B and antistreptol- infection (small percentage)
ysin O titers (anti-DNase B and ASO, anti- • In North America the etiologic agent is pri-
bodies to streptococcal extracellular marily S. aureus
products)
Management • Common (i.e., crusted or nonbullous) impe-
• Penicillin remains the drug of choice (docu- tigo: Initial lesion is a superficial papulove-
mented cases of penicillin-resistant group A sicular lesion that ruptures easily
streptococcal infections still do not exist) • The lesion becomes purulent and covered
• First-generation cephalosporin may be an with an amber-colored crust (Fig. 9.15)
effective alternative • Bullous impetigo: Superficial fragile bullae
Streptococcosis containing serous fluid or pus form and then
• Occurs in children younger than 3 years
• Young infants may not present with classic
pharyngitis a
Fig. 9.14 Scarlet fever: Fine erythematous punctate erup-

tion with dry, rough texture to the skin that resembles the feel Fig. 9.15 (a) Impetigo: Honey-crusted lesions under the
of coarse sandpaper and scarlet macules overlying the gener- nostril and on the cheek. (b) Impetigo: Honey-crusted lesions
alized erythema on the arm and trunk
298 M. B. Laurens
rupture to form round, very erythematous

erosions
• The lesions usually located in exposed areas,
especially the face and extremities
• Lesions usually often spread due to
autoinoculation
Treatment
• Topical mupirocin or retapamulin for local-
ized lesions
• Multiple localized lesions may require sys-
temic treatment such as cephalexin or
clindamycin that covers both GAS and staph-
ylococcal infections
Fig. 9.16 Perianal bacterial dermatitis: 4-year-old presents
• Should not go back to school until at least 12 h with rectal pain, itchiness, and discomfort when sitting;
after beginning appropriate antimicrobial physical exam shows bright red, sharply demarcated rash
• Patient should avoid close contact with other around the anal area. Strep test was positive
children if possible
Management
Perianal Bacterial Dermatitis • Treatment with empiric oral cephalexin is
(Formerly Called Perianal effective for most staph and strep; if rapid
strep is positive, can use oral penicillin or
Streptococcal Dermatitis)
amoxicillin
Background • Topical mupirocin three times per day for
• May be caused by S. pyogenes (GAS) or S. 10 days
aureus, occurring in children • Follow-up is necessary because recurrences
6 months–10 years are common
• Often misdiagnosed and treated
inappropriately
• Early antibiotic treatment results in dramatic
rysipelas GAS
E
and rapid improvement in symptoms Clinical presentation
• Erythema and edema
• Sharply defined and elevated border tender to
• Perianal rash, itching, and rectal pain; blood-
palpation
streaked stools may also be seen in one-third
• Systemic signs such as fever are often present
of patients
• Lymphangitis may occur
• Bright red, sharply demarcated rash around
the anal area (Fig. 9.16) Management
• Systemic antibiotic therapy is required
Diagnosis
• Parenteral antibiotics may be needed, espe-
• A rapid streptococcal test of suspicious areas
cially in immunocompromised patients
can confirm the diagnosis if etiology is GAS
(vast majority of cases)
• Routine skin culture is an alternative diagnos-
tic aid
Streptococcal Toxic Shock Syndrome • Empiric therapy with broad-spectrum IV

antibiotics to cover both streptococcal and
Background staphylococcal infections, e.g., clindamycin
• GAS TSS is a form of invasive GAS disease IV plus penicillin G IV
associated with the acute onset of shock and • Immune globulin intravenous (IGIV) also
organ failure may be used as adjunctive therapy
Risk factors
• Injuries resulting in bruising or muscle strain Pediatric Autoimmune
• Surgical procedures Neuropsychiatric Disorders
• Varicella infection Associated with Streptococcus
• NSAID use
Infections (PANDAS)
• Streptococcal exotoxins that act as superanti-
gens cause release of cytokines leading to Background
capillary leak, leading to hypotension and • PANDAS describes a group of neuropsychi-
organ damage atric disorders, in particular, obsessive com-
pulsive disorder (OCD), tic disorders, and
Tourette syndrome, that are exacerbated by
• Fever
GAS infection
• Abrupt onset of severe pain, often associated
• Diagnostic criteria for PANDAS include:
with a preceding soft-tissue infection, e.g.,
–– Tourette syndrome; abrupt onset in
cellulitis or osteomyelitis
childhood
• Know: Patient may be normotensive initially,
–– Relationship between GAS infection and
but hypotension develops quickly
episodic symptoms confirmed by RADT,
• Erythroderma, a generalized erythematous
throat culture, skin culture, or serologic
macular rash, may develop
testing
Diagnosis –– Evaluation for GAS infection should be
• Leukocytosis with immature neutrophils considered in children who present with
• Elevated serum creatinine values the abrupt onset of OCD or tic disorder
• Hypoalbuminemia
Management
• Hypocalcemia
• Treatment of the GAS infection and neuro-
• Elevated creatine kinase concentration
psychiatric therapy
• Myoglobinuria, hemoglobinuria
• Behavioral therapy and pharmacological
• Positive blood cultures
therapies, including:
• Diagnosis of GAS TSS requires isolation of
–– Selective serotonin reuptake inhibitors
GAS, e.g., blood or CSF
(SSRIs) for OCD
Treatment for GAS TSS –– Clonidine for tics
• Aggressive fluid replacement is essential to
maintain adequate perfusion to prevent end-
ecrotizing Fasciitis
N
organ damage
• Vasopressors also may be required Background
• Immediate surgical exploration and debride- • A form of invasive bacterial disease that is
ment are necessary, and repeated resections often polymicrobial. This infection is charac-
may be required terized by extensive local necrosis of subcu-
taneous soft tissues
300 M. B. Laurens
• Typically caused by GAS and/or mixed aero- –– Unpasteurized milk and soft cheeses
bic and anaerobic flora, including Clostridium, –– Undercooked poultry
Staphylococcus. Salt water necrotizing fasci- –– Deli-style, prepared meats
itis contains Vibrio species. Freshwater nec- –– Asymptomatic vagina carrier in pregnant
rotizing fasciitis contains Aeromonas women

• Fever, hypotension, malaise, and myalgias • Neonatal early onset infection < 7 days causes
• Rapidly increasing pain; erythematous skin preterm birth, sepsis, or pneumonia with
that progresses to blisters, bullae, and crepi- 14–56% fatality. Characteristic granulomato-
tus with subcutaneous gas sis infantisepticum rash with papules
• Neonatal late onset infection > 7 days causes
Laboratory findings meningitis with 25% fatality
• Leukocytosis with a predominance of Treatment
neutrophils • Ampicillin and aminoglycoside
• Elevated creatine kinase, lactate, and creati-
nine values
• Positive wound cultures Corynebacterium diphtheriae
• Diagnosis is clinical and requires a high • Gram-positive pleomorphic bacillus
degree of suspicion because of the rapid pro- • Humans are reservoirs
gression of infection • Rare due to immunization

• Early and aggressive surgical exploration and • Low-grade fever
debridement • Sore throat
• Triple antibiotic therapy with IV penicillin G, • Malaise
clindamycin, and an aminoglycoside is • Difficulty swallowing
recommended • Bilateral cervical lymphadenopathy (“bull
• Hemodynamic support if GAS TSS is neck”)
present • Grayish exudates over mucous membrane
• Repeat surgery is necessary until all necrotic • Bleeding after attempting to remove the
tissue has been removed membrane
• Antibiotic therapy should continue for sev- • Diphtheria toxins can cause myocarditis,
eral days after completion of surgical debride- necrosis, and peripheral neuritis
ment and may include penicillin G,
vancomycin, metronidazole, or imipenem/ Treatment
meropenem • If diphtheria is suspected, antitoxin (equine
hyperimmune antiserum IV) should be started
immediately to neutralize the toxins.
Listeria monocytogenes Administer erythromycin for 14 days also.
• Know: Close contacts should receive single
Background IM dose of penicillin G benzathine or oral
• Aerobic Gram-positive bacillus erythromycin regardless of their immuniza-
• Rare disease with case fatality of 16–20% tion status.
• Mode of transmission is mostly foodborne
Enterococcus Clinical presentation

• Painless papules and ulcers
Background • Painless black eschar with painless swelling
• Gram-positive cocci and induration
• Normal inhabitant of the GI tract
• Enterococcus faecalis and Enterococcus Treatment
faecium • Penicillin G or quinolones, e.g., ciprofloxacin
• Most neonatal enterococcal infections are
nosocomial and occur after 2nd week of life,
usually with bacteremia due to line infection Bacillus cereus
or necrotizing enterocolitis (common symp-
Background
toms in neonates include, fever, bradycardia,
• Soil-dwelling, Gram-positive rods, beta
apnea, and abdominal distention)
hemolytic bacterium
Associated infections • Produces GI symptoms due to enterotoxin
• Bacteremia in neonates production in vivo in the GI tract
• Catheter-associated bacteremia
• Endocarditis
• Vomiting with incubation period 1–6 h (the
• Intra-abdominal abscess
emetic form is commonly associated with
• UTI
fried rice left at room temperature)
Antibiotics • Diarrhea with incubation period 8–16 h
• Resistant to all cephalosporins and • Eye infection after traumatic eye injuries in
vancomycin contact lens wearers
• E. faecalis is susceptible to ampicillin
Diagnosis
• E. faecium is resistant to ampicillin. Treat
• Usually clinical
with vancomycin pending susceptibility
• B. cereus spores in stool
results unless vancomycin-resistant entero-
• Isolated toxins from suspected food items
coccus (VRE), which requires linezolid
• Sensitivity testing is imperative because of Treatment
resistance • Self-limited and requires no antibiotics
• Sensitive enterococcal sepsis or endocarditis
must be treated with penicillin, ampicillin, or
vancomycin + gentamicin Arcanobacterium haemolyticum
Background
Bacillus anthracis • A. haemolyticum can be mistaken with strep
pharyngitis or scarlet fever
Background • Gram-positive bacillus
• Large positive rods (bacilli) that cause anthrax • Grows slowly as small colonies with narrow
• Types of anthrax: Cutaneous anthrax, pul- bands of hemolysis on blood-enriched agar
monic, and GI • Growth enhanced by culture on rabbit or
• Inoculation occurs from handling contami- human blood with incubation in 5% CO2
nated substance, e.g., wool, and in cases of
bioterrorism, via mail
302 M. B. Laurens
Clinical presentation • Cranial nerve palsies

• Common in teenagers and young adults • Generalized weakness with ventilatory
• 0.5–3% of acute pharyngitis failure
• Except for absence of palatal petechiae and
strawberry tongue, the disease indistinguish- Diagnosis
able from that caused by group A • Stool toxin detection
Streptococcus
• Fever Treatment
• Pharyngeal exudates • Botulism immune globulin (BIG) IV should
• Cervical lymphadenopathy be started as early as possible if clinically
• Scarlatiniform or maculopapular pruritic rash suspected
in 50% of cases; usually spares the palms and • Antibiotics (gentamicin) can potentiate toxin
soles paralytic effect
Treatment
• Macrolides: Erythromycin or azithromycin
Foodborne Botulism
Background
ANAEROBES • Most common source is home canned food
• Symptoms develop 12–36 h after toxin
Clostridium botulinum ingestion
• Wound botulism is similar, except the incuba-
Background tion period between 4 and 14 days
• C. botulinum is an anaerobic Gram-positive
rod that survives in soil and marine sediment
• Initial symptoms: Dry mouth, nausea, and
by forming spores
diarrhea
• Human botulism is caused by neurotoxins A,
• Bilateral cranial nerve palsies
B, E, and, occasionally, F
• Eye diplopia and blurring vision
• Dysphagia
Infant Botulism • Upper extremity weakness
• Respiratory dysfunction
• Ingestion of honey or exposure to contami- • Lower extremity dysfunction
nated soils increases the risk
• Age between 3 weeks and 6 months Treatment of botulism in older patients
• Symptoms develop 3–30 days from the time • Equine trivalent antitoxin (types A, B, and E)
of exposure • Wound debridement for wound botulism is
recommended
• Constipation usually the initial finding
• Feeding difficulty is a common presenting Clostridium perfringens
symptom
Background
• Hypotonia
• Gram-positive, rod- shaped, anaerobic, spore-
• Increased drooling
forming bacterium
• Weak cry
• Spores found in raw meat and poultry
• Truncal weakness
• Incubation period 8–12 h
Clinical presentation • Penicillin G or metronidazole

• Sudden onset of diarrhea • Muscle relaxants
• Crampy abdominal pain
Prevention of tetanus
Management • Routine immunization with DTaP and Tdap
• Resolves within 24 h
• Rehydration Prevention in wound injuries guideline
• Tetanus vaccine +/− tetanus immunoglobulin
(TIG)
Clostridium tetani –– Dirty wound, immunization is unknown or
less than three tetanus shots: Give TIG +
Background tetanus vaccine
• C. tetani, an obligate anaerobic Gram-positive –– Dirty wound, immunized > 5 years and
bacillus, is the pathogen responsible for < 10 years: Immunize, no TIG
tetanus –– Dirty wound, immunized < 5 years: No
• Nonencapsulated and forms spores that resist treatment
heat, desiccation, and disinfectants –– Clean wound, immunized < 10 years: No
• Contaminated deep puncture wounds, open treatment
wounds, soil, and animals (wool) containing –– Clean wound, immunized > 10 years:
spores are the most common sources of this Immunize, no TIG
bacteria
Neonatal tetanus
• Contaminated umbilical cord is a common C lostridium difficile
source of infection
Background
• Poor feeding (poor suck and swallowing due
• Gram-positive anaerobes
to muscle spasm)
• Colonization
• Constant crying
–– Around 50% of infants younger than 1 year
• Decreased movement
are colonized
• Spasm and rigidity
–– Carriage decreases by 1–5% by 2 years of
Generalized tetanus age
• Trismus (lockjaw) • Risk factors:
• Sardonic smile (risus sardonicus) –– Having infected roommate or having
• Severe muscle spasm symptomatic patient in the same ward
• Opisthotonos (severe hyperextension) –– Antibiotics, e.g., beta-lactams drugs,
• Laryngeal spasm can lead to airway obstruc- clindamycin, and macrolides
tion and death –– Underlying bowel disease or surgeries
• Tetanic seizure is severe; tonic contractions • Symptomatic disease is due to toxins A and B
with high fever produced by the organism
• Diagnosis is always clinical
Treatment • Asymptomatic colonization is common in
• Human tetanus immune globulin infants and young children
immediately • Watery diarrhea
304 M. B. Laurens
• Abdominal cramps • Head and neck

• Abdominal tenderness –– Retropharyngeal abscess
• In severe cases: –– Peritonsillar abscess
–– Systemic toxicity –– Dental abscess
–– Bloody diarrhea –– Ludwig angina
–– Toxic megacolon, perforation, or even • CNS
death are complications of pseudomembra- –– Brain abscess
nous colitis –– Subdural and epidural empyema
• Lung
Diagnosis –– Aspiration pneumonia
• Documenting toxin A and B in stool using –– Lung abscess
PCR or nucleic acid amplification tests –– Pleural empyema
(NAATs) (for toxin genes) • Abdomen
• Endoscopic findings of pseudomembranous –– Peritonitis
enterocolitis –– Appendicitis
• Young children < 2 years are commonly colo- –– Intra-abdominal abscess
nized with C. difficile • Skin and soft tissue
–– Infected bite wound
Treatment –– Necrotizing fasciitis
• Initial episode, non-severe: Oral –– Cellulitis
metronidazole • Antibiotics with anaerobic activity
• Oral vancomycin with or without metronida- –– Clindamycin
zole can be used in severe cases –– Penicillin
• Recurrence: Oral vancomycin can be used –– Ampicillin–sulbactam
alone or with rifaximin, or fecal microbiota –– Amoxicillin–clavulanic acid
transplantation –– Metronidazole
Prevention
• Hand washing with water and soap
• Know: Alcohol-based product are not effec- C ampylobacter Species
tive against the organism
• Diluted bleach solution is the best for decon- Background and epidemiology
tamination of surfaces • Campylobacter jejuni (Gram-negative motile
• Limit antibiotic use bacilli)
• Infected children should be excluded from • One of the most common agents associated
childcare facility for the duration of diarrhea with bacterial gastroenteritis
• Common sources: Uncooked poultry (chicken
and turkey), unpasteurized milk, dogs and cats
GRAM-NEGATIVE BACTERIA • Incubation period: 2–5 days
Gram-Negative Anaerobes Clinical presentation

• Bloody diarrhea
• Bacteroides • Abdominal pain (may mimic inflammatory
• Fusobacterium anaerobes bowel disease in severe cases)
• Causes a variety of clinical manifestations • Tenesmus
depending on the location • Fever
Diagnosis Clinical presentation (psittacosis)

• Stool culture in a selective media at tempera- • Fever
ture 42 °C incubated in gas mixture O2 and • Nonproductive cough
CO2 • Headache
• Malaise
Treatment • Extensive interstitial pneumonia can occur
• Azithromycin and erythromycin shorten ill- • Pericarditis, hepatitis, and encephalitis (rare)
ness duration and prevent relapse
Diagnosis
• Serology, nucleic acid amplification tests,
Chlamydia pneumoniae PCR
Background and epidemiology Treatment

• Transmitted from one person to another via • Doxycycline preferred therapy, including
respiratory secretions children < 8 years
• 50% of adults have antibody evidence of • Macrolides for pregnant women
exposure
Clinical presentation onjunctivitis Due to Chlamydia

C
• Patient may be asymptomatic or mildly to trachomatis
moderately ill
• Illness is usually prolonged with cough per- Background and epidemiology
sisting for 2–6 weeks • The most frequently identified infectious
• Pneumonia and pulmonary rales cause of neonatal conjunctivitis
• Acute bronchitis and bronchospasm • Transmitted perinatally from infected
• Less commonly: Nonexudative pharyngitis, mothers
laryngitis, otitis media, and sinusitis
Diagnosis • The symptoms typically develop 5–14 days
• Fourfold increase in IgG titer from acute to after birth
convalescent • Conjunctival edema
• IgM titer of ≥ 1:16 • Hyperemia
• Cross-reactivity and persistent antibody • Watery-to-mucopurulent discharge
makes diagnosis problematic • A pseudomembrane may form and bloody
discharge may be present if infection is
Treatment prolonged
• Macrolides, doxycycline, or tetracycline
Management
• Oral erythromycin × 14 days or azithromycin
Chlamydophila psittaci × 3 days
• Know: Topical prophylaxis with erythromy-
Background
cin or silver nitrate given to all infants to pre-
• C. psittaci is obligate intracellular bacterial
vent neonatal gonococcal conjunctivitis is
pathogen
ineffective against chlamydial conjunctivitis.
• Birds are major reservoir of C. psittaci, e.g.,
Suctioning may increase comfort and improve
parakeets and parrots
feeding.
• Animals such as goats and cows may become
infected
306 M. B. Laurens
Pneumonia Due to C. trachomatis Clinical presentation

• Females: Vaginitis in prepubertal girls, ure-
Background thritis, cervicitis, endometritis, salpingitis,
• Small, Gram-negative, obligate intracellular proctitis, and perihepatitis (Fitz–Hugh–Curtis
organisms syndrome). Can progress to pelvic inflamma-
• Transmitted to the infant from the birth canal tory disease
• Generally presents as a subacute infection • Males: Urethritis, epididymitis, and proctitis
2–19 weeks after birth • Reiter syndrome (arthritis, urethritis, bilateral
conjunctivitis)
Clinical presentation • Lymphogranuloma venereum (LGV):
• Rhinorrhea, congestion, or conjunctivitis Ulcerative lesion on genitalia followed by
• Tachypnea tender, unilateral lymphadenopathy
• Staccato cough
• Crackles (rales) Diagnosis
• Wheezing (rare) • NAATs of vaginal, endocervical, and male
• Preterm infants may have episodes of apnea intraurethral specimens; urine specimens
Diagnosis Treatment
• Chest radiography reveals infiltrates and • Doxycycline 100 mg per os BID for 7 days
hyperinflation • Azithromycin single dose 1 g
• Laboratory testing may reveal:
–– Peripheral eosinophilia
–– Elevated serum immunoglobulins Trachoma
• A positive NP direct fluorescent antibody
(DFA) test or culture is considered Background
diagnostic • Chronic keratoconjunctivitis caused by the
obligate intracellular bacterium C. trachomatis
Treatment • Disease transmission occurs primarily between
• Antibiotic treatment should be started pre- children and the women who care for them
sumptively on clinical grounds • Trachoma is the most common infectious
• Same antibiotic regimens as for neonatal cause of blindness worldwide
conjunctivitis
• If untreated, symptoms can last for months Clinical presentation
and include persistent hypoxemia • Chronic follicular keratoconjunctivitis with
• Remember: Diagnosis of chlamydial pneu- corneal neovascularization resulting from
monia in an infant necessitates treatment of untreated or chronic infection
the infant’s mother and her sexual partner • Blindness occurs in up to 15% of those
infected
• Trachoma rarely occurs in the USA
Chlamydia Genitourinary Tract
Diagnosis
Infection
• Clinical diagnosis and NAATs can confirm
Background the causative agent
• Sexual transmission • The cicatricial phase has unique clinical fea-
tures (eyelid scarring, eyelid buckling, lashes
rubbing on eye), which lead to definitive • May be coinfected with other sexually trans-
diagnosis in most cases mitted organisms, most commonly, C.
trachomatis
Treatment • Positive leukocyte esterase usually seen in
• Azithromycin single dose 20 mg/kg urine specimen
• Diagnosis of gonococcal urethritis with
NAATs
eisseria gonorrhoeae (Gonococcal
N • Presence of intracellular diplococci in ure-
Infections) thral discharge
• Treatment is ceftriaxone 250 mg IM × 1 plus
Background azithromycin 1 g × 1
• N. gonorrhoeae is a Gram-negative
diplococcus Epididymitis (gonococcus)
• Gonococcal infection is the second most • Dysuria and a mucopurulent discharge
common bacterial disease in the USA classi- • Scrotal edema with scrotal, inguinal, or flank
fied as nationally reportable and notifiable pain
• Highest prevalence in youth, especially • Urinalysis may demonstrate WBCs
females between 15 and 19 years of age • In most cases this infection is transmitted
• The incubation period is 2–7 days sexually and may be an extension of
• A child abuse evaluation must be performed urethritis
in any prepubertal case
Gonococcal proctitis
Neonatal conjunctivitis • Most cases of proctitis due to N. gonorrhoeae
• Conjunctivitis due to mucosal transmission occur in homosexual males
during vaginal delivery • Clinical presentation
• Topical antibiotics (erythromycin, silver nitrate, –– Anal discharge
or tetracycline) to the eyes of a newborn within –– Rectal bleeding
1 h of birth can prevent the infection –– Anorectal pain
• Treatment is ceftriaxone 125 mg IM × 1 –– Tenesmus
–– Constipation
Gonococcal pharyngitis
• Genital–oral activity is the major risk Disseminated gonococcal infection (DGI)
• Infection is asymptomatic in most cases • DGI infection occurs in 0.5–3% of people
• Patients who have gonococcal pharyngitis infected with N. gonorrhoeae
have a significant public health impact • DGI usually causes an asymptomatic genital
• Gonococcal pharyngitis patients at risk for infection
developing disseminated gonococcal infec- • Migratory arthritis (wrist, ankle, and knee)
tion (DGI) are the most common locations
• Pharyngeal infection clears spontaneously • Dermatitis
within 12 weeks • Tenosynovitis
• Treatment is ceftriaxone 250 mg IM × 1 • Fever and chills may occur
• Elevated WBC count
Gonococcal urethritis • DGI occurs more commonly in females
• Dysuria and a mucopurulent penile
discharge
308 M. B. Laurens
Screening methods for infection N. gonorrhoeae • True rigors

and Chlamydia –– Shaking chills that cannot be stopped
• Culture is the gold standard for diagnosing C. voluntarily
trachomatis –– Prolonged (10–20 min)
• Standard collection sites include the endocer- • Neck pain
vix, male and female urethra, nasopharynx, –– Severe pain in the neck, back, or extremities
conjunctiva, vagina, and rectum –– May manifest in younger children as
• NAATs amplify nucleic acid sequences spe- refusal to walk
cific for the organism of interest –– Meningismus: In patients older than
• The ease of urine collection, together with the 3 years, the classic signs of Kernig and
high sensitivity of NAATs, has made these Brudzinski may be elicited
tests the preferred method for screening • Vomiting
• The presence of Gram-negative intracellular –– May be associated with headache or
diplococci on microscopy suggests the diag- abdominal pain without diarrhea
nosis of gonococcal infection • Cushing triad:
–– Bradycardia
–– Hypertension
. meningitidis (Meningococcal
N –– Respiratory depression
Infections) • Purpura fulminans (meningococcemia)
–– Aggressive spread of purpura to large areas
Background with ischemic necrosis
• Aerobic Gram-negative diplococcus N. –– Sudden drops in blood pressure
meningitidis –– Acute adrenal hemorrhage (Waterhouse–
• Natural commensal organism living in the Friderichsen syndrome)
nasopharynx of humans
• Children younger than 2 years of age have a Diagnosis
nearly fivefold greater risk of contracting • Culture of the organism from a normally ster-
meningococcal disease than the general adult ile site is the gold standard for bacteriological
population diagnosis
• Risk of transmission: Crowded living condi- • CSF study:
tions, e.g., college dormitories, military –– CSF WBC counts are elevated in most
barracks patients who have meningitis
–– CSF WBC counts are low or even normal if
Clues to investigate for invasive meningococcal the disease is severe and rapidly
infection progressive
• Rash –– Markedly low glucose and elevated protein
–– Any rash appearing in the context of a sud- values are associated with the diagnosis of
den febrile illness should raise concern meningitis
–– Meningococcal rash is typically present • All patients with meningococcal disease or
within 24 h of any symptomatology meningitis must be tested for CH50 or CH100
–– Petechiae may be intraoral or conjunctival assay (20% of children with meningococcal
or be hidden in skinfolds disease will end having a complement
–– Early rash may not be petechial deficiency)
Management aemophilus influenzae

H
• Know: Antibiotics and fluids should not be
delayed Background
• Penicillin is effective treatment for both • Pleomorphic Gram-negative coccobacillus
severe meningococcal septicemia (SMS) and spread via respiratory tract secretions
meningococcal meningitis if the diagnosis is • Formerly the most common cause of menin-
certain gitis and serious bacteremia in children
• Broad-spectrum antibiotics effective against • Introduction of the H. influenzae vaccine
N. meningitidis and other potential pathogens quickly reduced the incidence of encapsu-
are indicated (e.g., ceftriaxone, cefotaxime, lated H. influenzae type b
and vancomycin) • Nontypeable strains are still responsible for a
• Emergency care evaluation and preferably large number of mucosal infections, includ-
transported via emergency medical services ing conjunctivitis, otitis media, sinusitis, and
to allow for prompt delivery of IV fluids and bronchitis
airway management if the condition is
suspected Bacterial meningitis
• Large isotonic fluid boluses (20 mL/kg) over • Peak age is less than 1 year
the first 5 min • Mortality rate around 5%
• Inotropic/vasoactive agent such as dopamine • Common complications include: Subdural
or dobutamine empyema, brain infarct, cerebritis, ventriculi-
• Hydrocortisone may be beneficial in children tis, brain abscess, and hydrocephalus
respond poorly to vasopressors • Long-term sequelae occur in 15–30% of sur-
vivors with sensorineural hearing loss; others
Prevention and indications for meningococcal include language disorders, intellectual dis-
vaccines ability, and developmental delay
• MenACWY vaccine is routinely recom- • Dexamethasone before or with antibiotics
mended at 11–12 years of age; 2 vaccines such as ceftriaxone or cefotaxime to prevent
licensed for children and adults, 1 dose hearing loss and neurologic sequelae
–– Can give as young as 2 months as a 4-dose
series for high risk (complement defi- Epiglottitis
ciency, asplenia, HIV, travel to endemic • Hib was the predominant organism (> 90%)
area) in pediatric epiglottitis before vaccine intro-
• MenB vaccine is optional and preferred for duction. Since that time, other bacteria,
16–18 years of age, 2-dose series including S. pneumoniae, GAS, S. aureus,
–– Can give as young as 10 years for high risk and Moraxella catarrhalis, can cause
(complement deficiency, asplenia, out- epiglottitis
break, lab workers); 2- or 3-dose series for • Occurs primarily in children aged 2–7 years.
high risk • The clinical triad of drooling, dysphagia, and
• Antibiotic prophylaxis, e.g., rifampin, cipro- distress is the classic presentation
floxacin, azithromycin, or ceftriaxone should • Fever with associated respiratory distress or
be used for contacts: air hunger occurs in most patients
–– Childcare contact • Treatment in patients with epiglottitis is
–– Direct exposure to oral secretions of indi- directed toward relieving the airway obstruc-
viduals with meningococcal disease (such tion and eradicating the infectious agent
as personnel providing mouth-to-mouth
resuscitation)
310 M. B. Laurens
• Optimally, initial treatment is provided by a • Cefotaxime or ceftriaxone is the antimicro-

pediatric anesthesiologist and either a pediat- bial of choice
ric surgeon or a pediatric otolaryngologist • Meropenem or chloramphenicol is another
option
Buccal infections • Amoxicillin is the drug of choice for noninva-
• Buccal cellulitis previously was always sive diseases such as otitis media or sinusitis;
caused by H. influenzae infection before the if amoxicillin fails, uses antibiotics against
vaccine beta-lactamase-producing strains, e.g., non-
• Always associated with bacteremia if present typeable H. influenzae including amoxicillin/
• Present with palpable cellulitis on both clavulanate, TMP-SMX, azithromycin, cefu-
checks, purplish in color, and child looks very roxime axetil, cefixime, and cefpodoxime.
toxic
Rifampin antibiotic prophylaxis for contact
Periorbital cellulitis with invasive Hib infection
• Previously H. influenzae was a common • All members of household who did not
cause, now S. pneumoniae bacteria is the receive immunization
most common etiology associated with • Less than 4 years with incomplete
sinusitis immunization
• Minor trauma or insect bite of the eyelid usu- • Younger than 12 months who did not com-
ally associated with preseptal cellulitis due to plete primary Hib immunization
S. aureus or a Group A Streptococcus • Immunocompromised child
• Nursery school and childcare center if two
Pyogenic arthritis or more cases within 60 days (outbreak)
• H. influenzae was the most common cause of
septic arthritis in children less than 2 years of
age before Hib vaccine Mycoplasma pneumonia
Occult bacteremia Background
• Occult bacteremia with H. influenzae will • M. pneumoniae is the leading cause of pneu-
result in in 30–50% developing meningitis or monia in school age children and young
other deep or focal infection from occult adults
bacteremia • Infection is prevalent in persons living in
• All occult bacteremia from H. influenzae has group setting
to be treated immediately • Incubation period is 2–3 weeks
Pneumonia Clinical presentation
• Pneumonia from H. influenzae used to cause • Pulmonary manifestations
about one-third of bacterial pneumonia before –– Nonproductive cough
Hib vaccine and was associated with pleural –– Chills
effusion and positive blood culture in most –– Scattered rales
cases –– Skin rash
–– Bilateral infiltrate on chest radiograph
Treatment (in patient with life-threatening • Extrapulmonary manifestations
illness) –– Pharyngitis
• Remember: The organism produces beta lac- –– Rash
tamase, which makes amoxicillin ineffective –– Stevens–Johnson syndrome
–– Hemolytic anemia ordetella pertussis

B
–– Arthritis
–– CNS disease (encephalitis; cranial nerve Background
palsy, especially CN III) • Small Gram-negative coccobacillus that
infects only humans
Testing for mycoplasma • Spreads by aerosol droplets expelled while
• Mycoplasma DNA PCR nasal washing coughing or sneezing in proximity to others
• IgG and IgM serology or cold agglutinin • Incubation period of 7–10 days

• Mycoplasma lacks the cell wall and beta lac- • Catarrhal phase
tams are not effective –– Lasts from 1 to 2 weeks
• Azithromycin is the drug of choice –– Mild fever
–– Cough
–– The cough worsens as the patient pro-
Pasteurella multocida gresses to the paroxysmal phase
• Paroxysmal phase
Background
–– Lasts from 2 to 6 weeks
• Small Gram-negative coccobacilli; normal
–– Rapid fire or staccato cough
oral flora in animals, e.g., dogs and cats
–– 5 to 10 uninterrupted coughs occur in suc-
• Dog or cat bite is a common risk
cession, followed by a “whoop” as the
Clinical presentation patient rapidly draws in a breath
• Erythema, tenderness, and edema usually –– May occur several times per hour
develop rapidly within 24 h –– Can be associated with cyanosis, saliva-
• Regional lymphadenopathy and fever may tion, lacrimation, and post tussive emesis
occur –– Despite the severe spells, patients often
• Infection that occurs days after the bite is appear relatively well between episodes
usually caused by S. aureus – – Whoop is usually absent in infants less
than 6 months of age
Treatment – – Gasping, gagging, and apnea can occur
• Clean wound with soap and water • Convalescent phase
• Treatment should cover potential pathogens, –– Decreasing frequency and severity of the
e.g., P. multocida, S. aureus, and anaerobes coughing episodes
• Administration of antibiotic within 8–12 h of –– Lasts from weeks to months
injury may decrease the risk of infection
• Penicillin is the drug of choice for P. multo- Complications of pertussis
cida alone • Pertussis is most severe in infants < 6 months
• Amoxicillin–clavulanate is the drug of choice • Apnea
for suspected polymicrobial wounds, includ- • Pneumonia
ing cat bites • Seizures
• Clindamycin + TMP-SMX is appropriate for • Encephalopathy
children allergic to penicillin • Death
312 M. B. Laurens
Thoracic pressure-related complications Immunization

• Pneumothorax or pneumomediastinum • Because immunity to pertussis from the DTaP
• Subcutaneous emphysema series wanes over time, a booster dose is rec-
• Superficial petechial hemorrhage ommended at age 11–12 years
• Rib fracture
• Rectal prolapse
• Intracranial hemorrhage Brucellosis
• PCR of NP specimen collected with Dacron • Brucellosis is a zoonotic infection caused by
swab is diagnostic test of choice the bacterial genus Brucella
• PCR remains positive late in the course of the • Brucellosis caused by Gram-negative
illness bacillus
• Leukocytosis as high as 60,000 can be seen • The bacteria are transmitted from animals to
due to absolute lymphocytosis humans by ingestion of unpasteurized milk or
cheese, direct contact with an infected ani-
Management mal, or inhalation of aerosols
• Infants afflicted with pertussis often require –– B. melitensis (from sheep; highest
hospitalization for fluid, nutritional, and pathogenicity)
respiratory support –– B. suis (from pigs; high pathogenicity)
• If left untreated, most individuals will clear –– B. abortus (from cattle; moderate
B. pertussis spontaneously from the naso- pathogenicity)
pharynx within 2 to 4 weeks of infection –– B. canis (from dogs; moderate
• Antibiotics can shorten the course and attenu- pathogenicity)
ate the severity of pertussis if started early
and can shorten the period of contagiousness Clues to Brucella infection
• Once the paroxysmal phase begins, antibiot- • Fever of unknown origin
ics are not effective in altering the course of • Culture negative endocarditis
the disease • Individuals at greatest risk for brucellosis are
• Excluded from school for 21 days if untreated, those exposed to goats, sheep, cows, camels,
or for 5 days while taking antibiotic pigs, reindeer, rabbits, or hares, both in areas
• Azithromycin is the drug of choice: of endemic disease and in areas where the
–– Infant less than 6 months: 10 mg/kg per disease is not endemic
day as a single dose for 5 days • Bone/joint inflammation
–– Older infants and children: 10 mg/kg as a • Orchitis
single dose on day 1 then 5 mg/kg per day • Hepatic abscess
as a single dose on days 2–5 • CNS symptoms
Prophylaxis to close contacts is the same as the Diagnosis

treatment • Elevated liver enzymes is a common finding
• Infants less than 1 year • Blood culture (alert laboratory if suspecting
• Pregnant women Brucella, as lab staff easily infected)
• Immunocompromised • Serology is most commonly used
• Underlying lung disease • PCR in development
Treatment
• Children > 8: doxycycline + rifampin for
6 weeks
• Children < 8: TMP/SMX + rifampin for
6 weeks
• Add gentamicin for serious infection or
complications
Bartonella henselae
Cat-Scratch Disease
Background
• B. henselae is Gram-negative rod or bacilli
with a polar flagellum
• Kittens or cats less than 1 year old are most
common source, also dogs
• Transmission can occur by petting alone with
subsequent self-inoculation via a mucous
membrane, skin break, or conjunctiva
• Clue for the diagnosis: Contact with cats and
lymphadenopathy
Clinical presentation Fig. 9.17 14-year-old female with large tender axillary
lymphadenopathy, she has kittens at home
• Regional lymphadenopathy (cervical and
axillary are common locations) (Fig. 9.17) • Lymphadenopathy remains regional and typi-
–– Usually large and may be tender, warm, cally resolves within 2–4 months but may last
and erythematous up to 6–12 months
–– Suppuration can occur in 30% of cases
–– Node may remain enlarged for several months Diagnosis
–– Papule at the site of scratch may precede • Indirect fluorescence assay (IFA) testing and
the development of lymphadenopathy enzyme-linked immunoassay (ELISA) are
• Parinaud oculoglandular syndrome: used to detect serum antibody to B. henselae
–– Painless nonpurulent conjunctivitis • An antibody titer that exceeds 1:64 suggests
–– Ipsilateral preauricular lymphadenopathy recent Bartonella infection
• Other clinical presentations • Lymph node biopsy generally is not indicated
–– Fever of unknown origin in typical cases
–– Hepatic splenic microabscesses
–– Painful osteolytic lesions Treatment
• Patients may recall being scratched, licked, or • Cat-scratch disease is self-limited
bitten by a cat in the previous 2–8 weeks • Use of azithromycin can decrease lymph
• Fever, anorexia, headache, sore throat, or node size faster than natural course
arthralgia may occur
314 M. B. Laurens
• Doxycycline or rifampin may also treat • Burn wounds

• Immunocompromised should receive • Ventilator-associated pneumonia
antibiotics
Clinical presentation according to the site of
Surgical treatment infection
• Remember: Incision and drainage are not rec- • Pseudomonas keywords
ommended (risk of sinus tract and persistent –– Nail-puncture wound through tennis shoes
drainage) –– IV drug abuse, with endocarditis or
• Aspiration will be diagnostic and therapeutic; osteomyelitis
repeated aspirations may be performed if pus –– Diabetes with otitis media
reaccumulates and pain recurs –– Leukemia with ecthyma gangrenosum
• Hot tub folliculitis
–– Clinical presentation:
Citrobacter ◦◦ The rash onset is usually 8 h to 5 days
after exposure to contaminated water
• Cause brain abscess in neonates ◦◦ Erythematous pruritic macules that
• Order computed tomography (CT) or MRI if progress to papules and pustules
CSF grow ◦◦ Rash usually spares face, neck, soles,
• Citrobacter otherwise is very rare disease and palms
◦◦ Usually confused with insect bites (his-
tory is important)
Klebsiella ◦◦ Rash clears spontaneously within
• A rare cause of pneumonia and meningitis 2–10 days
• Can cause UTIs but is less common than E. –– Self-limited, require no antibiotics
coli –– Acetic acid 5% compresses for 20 min
• Most Klebsiella are resistant to ampicillin twice a day for 4 days for symptomatic
relief
Antimicrobial therapy
Pseudomonas Species
• Piperacillin/tazobactam (Zosyn)
Background • Ceftazidime (third generation)
• Gram-negative organism • Cefepime (fourth generation)
• Found in the soil and freshwater • Carbapenems (meropenem, imipenem)
• Gains entry through hair follicles or via skin • Aminoglycosides (gentamicin)
breaks • Aztreonam
• Certain fluoroquinolones (ciprofloxacin,
Risk factors levofloxacin)
• Cystic fibrosis (see Chap. 20 “Pulmonology”)
• Associated with progressive deterioration of
pulmonary function Nontyphoidal Salmonellosis
• Associated with hot tub folliculitis
• Ocular infection from contaminated lenses Background
• Puncture wound osteomyelitis • Gram-negative bacilli that are usually motile
• In immunocompromised patients, e.g., bacteria
ecthyma gangrenosum • A common cause of diarrhea
• Hospitalized and debilitated patients • Incubation period 6–72 h
Mode of transmission • Diarrhea is more likely in children

• Contaminated poultry, beef, eggs, fruits, veg- • Abdominal tenderness, hepatosplenomegaly,
etables, bakery, and dairy products and a coated tongue
• Turtles, iguana, and exotic reptiles • Rose spots (pink, blanchable maculopapular
lesions that are 2–4 mm in diameter) are seen
Clinical presentation on the torso and abdomen
• Can be asymptomatic • Know: Neonatal typhoid generally presents
• Most common presentation is gastroenteritis within 3 days of birth with fever, emesis, diar-
• Abrupt onset of fever, nausea, and vomiting rhea, abdominal distention, pronounced hep-
• Abdominal cramps atomegaly, jaundice, and (sometimes)
• Moderate-to-severe watery diarrhea most seizures
common manifestation • Know: Absence of abdominal or intestinal
changes is not typical of typhoid
Diagnosis
• Stool may show leukocytes, mucus, and blood Diagnosis
• CBC; leukocytosis and shift to the left • Blood cultures are the mainstay of diagnosis,
• After symptoms the patient can be a carrier positive in 50% of those with the disease
for 4–5 weeks • Stool culture may increase yield
Indication of antibiotic therapy Treatment

• In infants less than 3 months • Treatment includes:
• Infant < 12 months with temperature > 39 °C –– Hydration and correction of fluid–electro-
• Hemoglobinopathies, e.g., sickle cell anemia, lyte imbalance
HIV, and neoplastic diseases –– Antipyretics and antibiotics
• Immunocompromised patients at any age • The choice of antibiotic, route, and duration
depends on the host, site of infection, and
sensitivities of the organism
Typhoid Fever • IV cefotaxime or ceftriaxone for 14 days is
appropriate
Background
• Multidrug resistant (MDR) strains, including
• Salmonella enterica serovar Typhi (S. Typhi)
resistance to ampicillin, TMP-SMX, cephalo-
• Mode of transmission
sporins, carbapenems, and fluoroquinolones
–– Poor sanitation and overcrowding
have emerged mostly from Asia. Only azithro-
–– Spread by fecal–oral contamination of
mycin works for these MDR strains
food or water by individuals who are carri-
• For severe typhoid with obtundation, stupor,
ers for S. Typhi in either stool or urine
coma, or shock:
–– Typhoid is endemic in many developing
–– Two-day course of IV dexamethasone may
areas
be life-saving
• Fever “can exceed 104 °F (40 °C)”
• Malaise
higella
S
• Chills Background
• Headache, anorexia, myalgias, and dry cough • Shigella is a Gram-negative bacillus
may be seen • S. dysenteriae and S. flexneri usually cause
• Abdominal pain is common bloody diarrhea
316 M. B. Laurens
• S. sonnei and S. boydii usually cause watery • Antimicrobial therapy for 5 days will shorten
diarrhea the duration and eradicate the organism from
• Ingestion of as few as 10 organisms can cause stool
diarrhea • Antimicrobial resistance testing guides
• Incubation period is 2–4 days therapy
• Outbreak can occur in childcare centers • Empiric ceftriaxone, ciprofloxacin or azithro-
mycin are usually effective
Mode of transmission • If there is an alternative to ciprofloxacin, it is
• Person to person not recommended for those less than 18 years
• Fecal–oral
• Anal–oral Childcare center
• House flies • Once Shigella is identified in a childcare cen-
• Contaminated fomites ter or household, all symptomatic individuals
in these environments should be cultured for
Clinical presentation Shigella
• Ranges from mild diarrhea to life-threatening • Anyone found to have Shigella cannot return
dysentery to the care center until the diarrhea has
• Fever stopped and stool culture test is negative
• Abdominal camps
• High-volume watery stools
• Small-volume bloody stool may follow Escherichia coli
24–48 h later
• Blood-mucoid stool is a common Background
presentation • E. coli is a Gram-negative, lactose ferment-
• Rectal prolapse occurs in 5–8% ing, motile rod, belonging to the
Enterobacteriaceae
Complications • E. coli is one of the most frequent causes of
• Hemolytic-uremic syndrome many common bacterial infections, including
• Seizures cholecystitis, bacteremia, cholangitis, UTI,
• Colonic perforation and traveler’s diarrhea; and other clinical
• Toxic encephalopathy infections such as neonatal meningitis and
pneumonia
Diagnosis
• Stool culture is diagnostic Acute bacterial meningitis
• Stool study with large number of neutrophils • The vast majority of neonatal meningitis
is suggestive but not specific cases are caused by E. coli and group B strep-
• Peripheral WBCs are usually elevated; ban- tococcal infections
demia is very common • Pregnant women are at a higher risk of colo-
nization with the K1 capsular antigen strain
Treatment of E. coli, which is commonly observed in
• Most infections with S. sonnei are self-lim- neonatal sepsis
ited and do not warrant antibiotics • Low-birth weight and a positive CSF culture
• Antimicrobial therapy is recommended for result portend a poor outcome
immunocompromised patients with shigellosis • Most survivors have subsequent neurologic
or developmental abnormalities
Pneumonia • The recurrence rate after a first E. coli infec-

• E. coli respiratory tract infections are uncom- tion is 44% over 12 months
mon and are almost always associated with E. • E. coli UTIs are caused by uropathogenic
coli UTI strains of E. coli
• E. coli causes a wide range of UTIs, includ-
Intra-abdominal infections ing uncomplicated urethritis, cystitis, pyelo-
• E. coli intra-abdominal infections often result nephritis, and urosepsis
from a perforated viscus (e.g., appendix,
diverticulum) or may be associated with intra- Other miscellaneous E. coli infections
abdominal abscess, cholecystitis, and ascend- • Septic arthritis
ing cholangitis • Endocarditis
• They can be observed in the postoperative • Soft tissue infections especially in patients
period after anastomotic disruption. Abscesses with diabetes
are often polymicrobial
• E. coli is one of the more common Gram-
negative bacilli observed together with
E. coli (O157:H7)
anaerobes
Background
Enteric infections
• Gram-negative rods
• Enterotoxigenic E. coli (ETEC) is a cause of
• Occurs in all ages
traveler’s diarrhea; azithromycin is the drug
• Transmitted via ingestion of contaminated
of choice; infants < 3 months can receive a
food (e.g., ground beef) or infected feces
third generation cephalosporin
• The disease linked to eating undercooked
• Enteropathogenic E. coli (EPEC) is a cause
beef and unpasteurized milk or apple juice
of childhood diarrhea; can be treated with
• Produces Shiga toxins; the most virulent
TMP-SMX
strain
• Enteroinvasive E. coli (EIEC) causes a
• The incidence of E. coli O157:H7
Shigella-like dysentery
> Shigella
• Enteroaggregative E. coli (EAEC) is primar-
ily associated with persistent diarrhea in chil- Clinical presentation
dren in developing countries, and • Usually begins as nonbloody diarrhea then
enteroadherent E. coli (EAEC) is a cause of becomes bloody
childhood diarrhea and traveler’s diarrhea in • Severe abdominal pain is common
Mexico and North Africa • Fever in one-third of the cases
• Enterohemorrhagic E. coli (EHEC) causes • May progress to hemorrhagic colitis in severe
hemorrhagic colitis or hemolytic-uremic syn- cases
drome (HUS) • HUS may occur
• Strains of STEC serotype O157:H7 have
caused numerous outbreaks and sporadic Management
cases of bloody diarrhea and HUS • No antibiotic is proven effective, and antibi-
otic use may increase risk of HUS
Urinary tract infections • Do not treat with antibiotics in most cases
• The urinary tract is the most common site of • Do not use antimotility agents
E. coli infection, and more than 90% of all
uncomplicated UTIs are caused by E. coli
infection
318 M. B. Laurens
Yersinia enterocolitica • Typhoidal tularemia (fever, chills, myalgias,

malaise, and weight loss)
Background
• Small Gram-negative coccobacillus Diagnosis
• It produces entero and endotoxins • Serology, e.g., ELISA or PCR
• Pigs are commonly infected
• Ingestion of raw or improperly prepared Treatment
food, such as pork (pork intestine or chitter- • Gentamicin or streptomycin for 10 days
lings), contaminated unpasteurized milk, and
Prevention
water
• Avoid tick-infested areas, check clothing for
Clinical presentation ticks, and use tick repellents
• Blood and mucus in stool • Avoid exposure to dead or wild mammals and
• Fever wear gloves if such exposure is necessary;
• Right lower quadrant pain hands should be thoroughly washed
• Leukocytosis afterward
• Mimics appendicitis
Treatment ocky Mountain Spotted Fever

R
• No treatment for isolated intestinal infection (RMSF)
• If < 6 months old, extraintestinal manifesta-
tion, sepsis, or immunocompromised, then Background and epidemiology
antibiotic is indicated • Tickborne rickettsial disease
• Cefotaxime or ceftriaxone • Transmitted by the American dog tick
(Dermacentor variabilis) east of the Rocky
Mountains and Pacific coast
Francisella tularensis • Spread by Rocky Mountain wood tick (D.
andersoni) in Rocky Mountain region
Background • Spread by Brown dog tick (Rhipicephalus
• Gram-negative pleomorphic bacillus that sanguineus) worldwide
causes tularemia or “rabbit fever” • Caused by Rickettsia rickettsii
• Found in many animals, especially rabbits • Peak transmission in summer
• Transmitted by ticks and blood-sucking flies
• Organism can be ingested or inhaled Clinical features
• Prevalent in the Southwest desert; Arkansas, • Early illness (days 1–4)
Missouri, and Oklahoma –– Fever
–– Malaise
Clinical presentation –– Headache
• Fever, chills, myalgias, and arthralgias –– Abdominal pain
• Irregular ulcers at the site of inoculation –– Myalgias
• Lymphadenopathy that suppurates and forms –– Rash appears 2–4 days after fever; 10–15%
an ulcer do not have rash
• Oculoglandular tularemia (unilateral con- –– Maculopapular rash starts at the wrists and
junctivitis, corneal ulceration) ankles, spreads centrally to palms and
• Pneumonic tularemia (dry cough, dyspnea, soles
and pleuritic-type chest pain) –– Rash becomes petechial and purpuric
• Late illness • Peak transmission in summer

–– Altered mental status • Incubation period is 5–14 days
–– Pulmonary edema, acute respiratory dis-
tress syndrome (ARDS) Clinical presentation
–– Multiorgan failure (CNS, kidney) • Similar to RMSF with early and late illness
(Table 9.2)
Laboratory • Maculopapular rash sparing the face that may
• Serology testing: Indirect fluorescent anti- spread to palms/soles; appears in 60% of chil-
body (IFA) for IgG at presentation and dren 5 days after fever begins
2–4 weeks later. Frequently negative during
1st week of illness Laboratory findings
• PCR blood may be helpful if positive but does • Leukopenia
not rule out infection, as the organism is • Neutropenia
intracellular • Thrombocytopenia
• Hyponatremia
Treatment • Elevated liver enzymes
• Start treatment before testing results return;
can be fatal within days Treatment
• Doxycycline is the treatment of choice even • Drug of choice is doxycycline, including
in children < 8 years children < 8 years
• Antibiotic is given for at least 5–7 days and at
least 3 days after fever resolves
• Best outcome when treatment started within Borrelia burgdorferi
5 days of illness
Lyme Disease
Complications
Background
• Vasculitis
• Tick-borne infection caused by spirochete B.
• Disseminated intravascular coagulation (DIC)
burgdorferi
• Death
• Transmitted by Ixodes species ticks in the
nymphal stage
Ehrlichiosis • Commonly seen in spring and summer
Background and epidemiology Table 9.2 Difference between Rocky Mountain spotted
fever and ehrlichiosis
• Gram-negative cocci
Rocky Mountain
• Transmitted by:
Difference spotted fever Ehrlichiosis
–– Lone star tick (Amblyomma americanum) Mode of Tick Tick
in South Central and Eastern United States. transmission
Also transmits for tularemia and southern Rash Very common, 60% of children
tick associated rash illness (STARI) including on palms
and soles
–– Blacklegged tick (Ixodes scapularis) in
Neutropenia Less common More common
Eastern United States. Also transmits for Thrombocytopenia Yes Yes
anaplasmosis, Lyme disease, and Anemia Present in ~15% Occurs in 50%
babesiosis later in illness
• Can transmit via blood transfusion and organ Hyponatremia Yes Yes
Liver enzymes May be elevated Usually elevated
transplantation Treatment Doxycycline Doxycycline
320 M. B. Laurens
• Common regions in the USA: Northeast to Mid- • AV block or meningitis: Doxycycline or cef-
Atlantic (> 90%), upper Midwest (Wisconsin triaxone for 14 days
and Minnesota), West Coast (California) • Arthritis: Doxycycline for 28 days (amoxicil-
• Incubation period: 11 days lin for 28 days if < 8 years)
Early localized disease stage I

• Erythema migrans (pathognomonic skin Treponema pallidum
lesion) either bullseye or clear center
• Myalgia Background
• Arthralgia • T. pallidum is spirochete mobile bacteria
• Mild fever • Mode of transmission:
–– Sexual contact
Early disseminated disease stage II (weeks to –– Transplacental (congenital)
months later) –– Exposure to infected blood or tissue
• Multiple erythema migrans lesions
• Meningitis (lymphocytic) Clinical presentation
• Cranial nerve palsies, e.g., Bell palsy • Congenital syphilis
• Peripheral neuropathy, e.g., foot drop –– Stillbirth, hydrops, preterm, or
• Heart block: first, second, or third degree asymptomatic
–– Hepatosplenomegaly
Late disseminated disease stage III –– Snuffles (nasal secretions)
• Arthritis –– Lymphadenopathy
• Oligo-migratory arthritis –– Mucocutaneous lesions
• Remember: Lyme disease can be confused –– Pneumonia
with juvenile idiopathic arthritis (JIA) –– Bone findings: Osteochondritis and
periostitis
Diagnosis –– Maculopapular rash prominent on hands
• Erythema migrans is pathognomonic and is and feet that are highly infective
an early lesion; antibodies not developed yet –– Late manifestations: Interstitial keratitis,
–– No need to test. Treat based on clinical deafness, Hutchinson teeth (peg-shaped
diagnosis incisors), anterior bowing of shins, fron-
• Serologic testing indicated to confirm early tal bossing, mulberry molars, saddle nose
and late disseminated disease. Two-tiered • Primary syphilis
testing: –– Genital chancre 3 weeks after exposure
–– Initial test is highly sensitive enzyme –– Painless papule that then become painless
immunoassay assay (EIA). If positive, then ulcer, which is very contagious
–– Western blot test, considered positive if • Secondary syphilis 2–10 weeks after the
either chancre heals
◦◦ 2 IgM bands positive, or –– Maculopapular rash involving palms and
◦◦ 5 IgG bands positive soles
–– Condyloma lata (wart-like plaques around
Treatment the anus or the vagina confused with con-
• Early localized: Doxycycline for 10 days dyloma acuminata seen in HPV)
(amoxicillin for 14 days if < 8 years) –– Generalized lymphadenopathy
• Isolated facial palsy: Doxycycline for • Tertiary syphilis (symptomatic late syphilis
14 days 15–30 years after initial infection)
–– Cardiovascular, CNS, gummatous lesions
Diagnosis and treatment • Mycobacteria, such as M. tuberculosis, are

• Screening methods: aerobic, non-spore-forming, non-motile, fac-
–– Rapid plasma reagin (RPR) and venereal ultative, curved intracellular rods measuring
disease research laboratory (VDRL) test 0.2–0.5 μm by 2–4 μm
correlate with disease activity • Retains many stains after decolorization
–– Other infections and autoimmune diseases with acid-alcohol, which is the basis of the
can cause false positive RPR or VDRL acid-fast stains used for pathologic
• Fluorescent treponemal antibody absorption identification
(FTA-ABS) test confirms the diagnosis, and • TB spreads most commonly via airborne
this test remains positive for life transmission
• Congenital syphilis: • TB is unlikely to spread from child < 4 years
–– Unlikely: No evaluation or treatment. of age due to limited tussive force
Maternal titer low/negative and history of • TB is likely to spread from infected adults to
adequate treatment, normal infant physical children (usually household or childcare
exam, and infant titer < 4-fold the maternal center)
titer
–– Less likely: Benzathine penicillin G single Risk factors
dose, no evaluation. Maternal history of • Foreign-born individuals in the USA have TB
adequate treatment > 4 weeks before deliv- rates 9.5 times higher than those of persons
ery, normal infant physical exam, and born in the USA
infant titer < 4-fold the maternal titer • HIV infection, treatment with TNF-alpha
–– Possible: Aqueous crystalline penicillin G antagonists such as infliximab and etanercept,
for 10 days; analysis of CSF, CBC, long and other immunocompromising conditions
bone radiographs: Mother not treated ade- • Recent latent tuberculosis infection (LTBI)
quately or treated < 4 weeks before deliv- • IV drug use
ery, normal infant physical exam, and • Certain medical conditions such as diabetes
infant titer < 4-fold the maternal titer and renal failure
–– Proven/highly probable: Aqueous crystal- • Incubation period from exposure to positive
line penicillin G for 10 days; analysis of test is 2–10 weeks
CSF, CBC, chest and long bone radio-
graphs; transaminase; neuroimaging; oph- Clinical presentation
thalmologic exam. Mother not treated • Only 5–10% of children older than 3 years of
adequately or treated < 4 weeks before age who have untreated LTBI progress to
delivery, or abnormal infant physical exam, disease
or infant titer 4-fold higher than maternal • Most LTBI progress to disease within
titer 1–2 years of initial infection
• Treatment with penicillin for acquired syphi- • The most common site of infection is the lung
lis, with doxycycline or tetracycline if aller- (up to 80%)
gic to penicillin • Pulmonary disease
–– Infants and adolescents are more likely to
be symptomatic than 5 to 10-year-old
Mycobacterium tuberculosis children
–– Cough (usually last 3 weeks or longer)
Background –– Hemoptysis
• M. tuberculosis, a tubercle bacillus, is the –– Low-grade fever
causative agent of tuberculosis (TB) –– Weight loss (rare)
–– Night sweats
322 M. B. Laurens
–– Loss of appetite –– Most children have positive tuberculin skin

–– Hilar or mediastinal adenopathy may be test (TST) results
seen –– Effusions are more common on the right
–– Cavity lesions and rarely bilateral
• Superficial lymphadenopathy –– The pleural fluid is exudative and
–– The most common extrapulmonary form lymphocytic
of TB –– A 6-month course of therapy is
–– Children who have TB lymphadenopathy recommended
tend to be older than those who have non- • Miliary tuberculosis
tuberculous mycobacterial –– Due to lymphohematogenous spread, it is a
lymphadenopathy disease of the young or immunocompro-
–– Common locations: Anterior cervical, fol- mised children
lowed by posterior triangle, submandibu- –– Miliary disease can present shortly after
lar, and supraclavicular primary infection
–– Lymph nodes usually measure 2–4 cm and –– Multiorgan involvement is common
lack the classic inflammatory findings of –– Clinical presentation:
pyogenic nodes ◦◦ Pyrexia
–– There may be overlying violaceous skin ◦◦ Hepatomegaly and splenomegaly
discoloration –– TST is insensitive because disseminated
–– Surgical node excision is not curative but disease can produce TST anergy
may be necessary to establish the diagnosis –– AFB culture from gastric aspirates can
–– Most children respond well to a 6-month have a yield as high as 50%
course of multidrug therapy, but occasion- –– A prolonged course of therapy
ally therapy must be extended to 9 months, (9–12 months) should be administered to
based on clinical response patients who have disseminated disease
• CNS disease • Skeletal TB
–– Tuberculomas, occurring in 5% of children –– The most common manifestations of skel-
who have CNS TB, appear as single rim- etal disease are:
enhancing lesions ranging from 1 to 5 cm ◦◦ Spondylitis
–– In TB meningitis, CSF analysis typically ◦◦ Arthritis
demonstrates lymphocytes, a low-glucose ◦◦ Osteomyelitis
concentration, and a high-protein value –– Most patients are in the second decade of
–– The most common findings on CNS life
imaging: –– Spinal involvement (Pott disease), which
◦◦ Hydrocephalus and basilar enhancement can affect even young children
◦◦ Vascular lesions involving the basal gan- –– Skeletal lesions can develop more than
glia and midbrain also are common 10 years after initial infection
–– TB should be considered in cases of child- –– MRI is the preferred imaging choice
hood stroke because it can demonstrate lesions months
• Pleural TB before plain radiographs
–– Seen more in older child and adolescent –– Chest radiographs are positive in 50% of
–– Can occur in isolation or concomitantly children who have skeletal TB
with pulmonary parenchymal disease –– TST results are usually positive
–– Symptoms include chest pain, fever, • Other forms of TB include:
cough, dyspnea, and anorexia. Auscultatory –– Abdominal
findings mimic those of bacterial –– Renal
pneumonia –– Cutaneous disease
TB testing –– A negative result never eliminates the pos-

• Cultures can be obtained by sequential spu- sibility of TB disease because many dis-
tum sampling or by gastric aspiration of early seminated forms of TB, including TB
morning secretions in the younger child meningitis, can induce TST anergy
• The bacillus grows slowly • False-negative TST results:
–– 6 to 8 weeks to grow on Lowenstein– –– Recent measles infection or vaccination
Jensen media –– High-dose corticosteroid treatment,
–– 2 to 3 weeks to grow in liquid media irradiation
• AFB stains include Kinyoun, auramine–rho- –– Immunosuppressive therapy
damine (Truant), and Ziehl–Neelsen –– Immunocompromising medical conditions
• Tuberculin skin test (TST) (Table 9.3) –– Disseminated tuberculosis
–– Measured in millimeters of induration (not • False-positive TST result:
erythema) –– Primarily in children exposed to nontuber-
–– Reading is 48–72 h after placement culous (environmental) mycobacteria
–– Preferred for children < 2 years –– Children recently received a bacillus
–– Know: If a child returns for TST interpreta- Calmette–Guérin vaccine
tion after 72 h and has induration meeting –– A boosting phenomenon: Children received
the criteria for positivity, the test is consid- multiple sequential TSTs
ered positive. –– First screen for exposure risk by history
before testing. Do not test all children
routinely
• Bacillus Calmette–Guérin (BCG) vaccine
Table 9.3 Positive tuberculin test reaction results in infants, –– TST can be interpreted normally in a child
children, and adolescents who received a single dose of BCG vaccine
Induration as a young child
Induration of 5 mm or Induration 10 mm more than –– Having received BCG as an infant may not
more or more 15 mm
Children in close Children < 4 years Children
explain a positive skin test result later in
contact with known or of age 4 years of life
suspected contagious age or older –– The assumption that BCG receipt is the
people with without any cause of a positive TST could lead to a lack
tuberculosis risk of treatment for high-risk children who
Children with suspected Children with other
tuberculosis either medical conditions,
potentially could benefit from LTBI
clinically or on chest including Hodgkin therapy
radiograph disease, • Whole blood interferon-gamma release assays
lymphoma, (IGRAs) have several potential advantages:
diabetes, renal –– Only one office visit is required
failure,
malnutrition –– There is no risk of the boosting
Children receiving Children born in, phenomenon
immunosuppressive or who travel to, –– More specificity for LTBI because the anti-
therapy or with high-prevalence gens in the IGRAs is shared less commonly
immunosuppressive countries
with nontuberculous mycobacteria and are
conditions, including
HIV not found on BCG
Children exposed • Chest radiographs
to adults in –– Children who have LTBI usually have nor-
high-risk mal-appearing chest radiographs
categories
324 M. B. Laurens
–– An isolated calcified lesion in a child who • Ethambutol can rarely cause optic neuritis
has a positive TST result can be treated as (decreased color perception is the first sign of
LTBI deterioration)
–– The most common abnormal radiographic • Pyridoxine supplementation indicated for
finding is hilar or mediastinal adenopathy exclusively breastfed infants, nutritional defi-
–– Other findings can include infiltrates, atel- ciencies, symptomatic HIV, and pregnant
ectasis, pleural effusions, cavities, or mili- females
ary disease
• TB exposure: Challenging clinical scenarios
–– Children younger than 4 years of age and • Adult in the household has infectious TB
immunocompromised children –– All children in the household should have
–– Should begin isoniazid (INH), pending chest radiographs and TSTs performed
results of repeat testing –– Children younger than 4 years of age
–– If the second test result is negative, medi- should be started empirically on INH and
cation can be discontinued rifampin until the TST is repeated in
–– Children experiencing TB exposure who 2–3 months
are older than age 4 years and immuno- – – If the second TST result is negative and the
competent can be observed off medica- child is immunocompetent, medication can
tions, pending the second test result in be discontinued
2–3 months – – If the TST result is positive or the child is
immunocompromised, INH and rifampin
Latent TB infection (LTBI) should be continued
• The child demonstrating a positive skin test • Infant whose mother has TB
result should be treated for LTBI to decrease –– The TST is helpful only if the result is pos-
the risk of disease progression later in life itive, which is very rare
• The mainstay of therapy for LTBI is –– If the mother has a positive TST result and
12 weeks of daily INH and weekly rifampin negative chest radiograph (LTBI), the child
• An alternative is 4 months of daily rifampin needs no evaluation
(for INH intolerant or resistance) –– If the mother has radiographic features
consistent with TB, the neonate requires
Treatment of TB evaluation for congenital TB
• The standard initial regimen for pulmonary –– If the infant does not have congenital TB,
and extrapulmonary TB: he or she should be separated from the
–– INH, rifampin, pyrazinamide (PZA), and mother until the infant is receiving INH
ethambutol and pyridoxine (if the mother is breastfeed-
–– INH and rifampin are administered for ing) and the mother is receiving appropri-
6 months, and PZA and ethambutol are ate multidrug therapy
stopped after the first 2 months –– Once the infant is receiving INH, separa-
• Exceptions: Treating children who have TB tion is unnecessary, and breastfeeding
meningitis, where treatment courses of should be encouraged unless INH resis-
7–12 months often are used tance is suspected
• Health-care workers (HCWs)
Side effects of antituberculous medications –– If positive TST results, they should receive
• INH, rifampin, and PZA are all hepatotoxic chest radiographs
–– If the chest radiograph is negative, the • Azithromycin or clarithromycin in combina-

HCW may be offered therapy for LTBI tion with ethambutol or rifampin if cannot be
after weighing the risks and benefits of resected
latent TB treatment in adults
–– If the chest radiograph is positive, the
HCW needs to be evaluated further FUNGAL INFECTIONS
Follow-up andida Species
C
• Children who have TB disease should be seen
monthly while receiving therapy to document • Candida albicans is the most commonly iso-
medication tolerance and adherence, weight lated species, and causes infections
gain, and achievement of appropriate (Candidiasis or thrush)
milestones • Systemic infections of the bloodstream and
major organs (invasive candidiasis or candi-
demia, particularly in immunocompromised
Mycobacterium Avium-Intracellulare patients)
• Candida appears as budding yeast cells and
Background pseudohyphae (Fig. 9.18)
• Mycobacterium avium-intracellulare com-
plex is the most common cause of nontuber-
culous disease in children Oral Thrush
• Caused by two types of bacteria:
Mycobacterium avium and Mycobacterium Background
intracellulare • Common in the first 6 postnatal months
• Usually occurs in children with impaired cell • Possibly due to infants’ immunologic
immunity, including very young children immaturity
< 5 years old
• Organisms are ubiquitous in soil
• Cervical lymphadenitis
–– Overlying skin is usually pink to
violaceous
–– Usually unilateral
–– Increase in size over several weeks
• Cutaneous infections
• Ear infections
• Disseminated and pulmonary infections (high
fever, night sweats, weight loss, lymphade-
nopathy, abdominal pain, diarrhea, and ane-
mia) can occur in immunocompromised
Fig. 9.18 Candida albicans in blood culture (Gram stain,
original magnification × 1000). Budding yeast cells (blasto-
Management conidia, black arrow) and pseudohyphae (white arrow).
• Complete resection of infected lymph node is (Courtesy of M. Nawar Hakim, MD, Department of
diagnostic and curative. Antibiotics are not Pathology, Texas Tech University Health Sciences Center, El
necessary! Paso, Texas, USA)
326 M. B. Laurens
Infection sources
• Contaminated bottle nipples, pacifier, or
dropper, e.g., vitamin dropper
• Infected mother’s nipples (although the inci-
dence is high in formula fed infants)
• Maternal vaginal colonization with
Candida
Recognize
• Recurrent or persistent oral thrush beyond
6–12 months raises the concern of immuno-
deficiency, especially if associated with fail-
ure to thrive or hepatosplenomegaly
Risk of infection Fig. 9.19 Thrush: Tiny focal white areas that enlarge to
• Use of inhaled steroid without adequate rins- white patches on oral mucosa; it was difficult to remove the
white spots with the tongue blade
ing afterward or oral antibiotics can cause
oral thrush
• Poorly controlled diabetes in adults can cause
Candida infection; however, it is not associ-
ated with gestational diabetes
• Infants may have trouble feeding in severe
cases
• Tiny focal white area that enlarge to white
patches on oral mucosa (Fig. 9.19)
• If scraped with a tongue blade, lesions are diffi-
cult to remove and leave behind an inflamed
base that may be painful and may bleed
• Examine the patient with diaper dermatitis
for oral lesions Fig. 9.20 Candidal diaper rash: Lesions consist of beefy-
red plaques with satellite papules
Treatment
• Oral nystatin Treatment
• Once-daily oral fluconazole is superior to • Topical nystatin, miconazole, clotrimazole
oral nystatin for resistant thrush
Vulvovaginitis
Candidal Diaper Dermatitis
Background
Clinical presentation • Common in pubertal and adolescent girls
• Lesions consist of beefy-red plaques, often • Risk factors
with scalloped borders –– Oral antibiotics
• Satellite papules and pustules may be –– Oral contraceptive
observed surrounding the plaques (Fig. 9.20) –– Pregnancy
• Maceration is often present, especially in –– Poor hygiene
intertriginous areas –– Diabetes
Clinical presentation • Wheezing, mucous plugging, fever, eosino-

• Vulvar/vaginal erythema and itching philia, transient lung infiltrates
• White, cottage cheese-like vaginal discharge • Underlying asthma or cystic fibrosis
• Allergic sinusitis
Treatment • Nasal polyps or sinus surgery
• Topical nystatin or clotrimazole • Dark nasal discharge
• Single dose of oral fluconazole for recurrent
or refractory cases Diagnosis
• Branched and septate hyphae seen on tissue
or BAL
Candidal Infections in Neonates • Molecular testing is definitive
• Galactomannan assay from BAL specimen
Background and serum
• Very low-birth-weight and premature infants
• Central line-associated bloodstream infection Treatment
(CLABSI): Obtain blood culture from periph- • Invasive aspergillosis: Voriconazole
ery and catheter • Allergic bronchopulmonary aspergillosis:
Corticosteroids
Treatment
• Remove the catheter if CLABSI
• Parenteral micafungin or amphotericin, pend- Malassezia furfur
ing identification and sensitivity testing
Overview
• Can cause tinea versicolor (see Chap. 26
Aspergillus “Dermatology”)
• Can cause neonatal infection in NICU babies
Background receiving total parenteral nutrition (TPN)
• Aspergillus species consist of ubiquitous with lipids
molds found in organic matter • NICU babies with M. furfur may present with
• Most common species affecting humans are fever, bilateral interstitial infiltrates, and
A. fumigatus and A. niger increased WBCs
• M. furfur requires olive oil overlay to grow
Mode of transmission
• Inhalation of fungus spores Management of infection in neonates
• Outbreaks can occur during hospital • Removal of catheters
construction • Stop lipid infusion
• Start amphotericin B or fluconazole
• Invasive aspergillosis: Immunocompromised
(neutropenia, graft-versus-host disease) Histoplasmosis
• Pulmonary, sinus, skin, intracranial
• Invasion of vasculature with erosion and Background
hemorrhage • Endemic areas: Ohio, Missouri, and
• Aspergillomas and otomycosis: Colonization Mississippi River valleys
in immunocompetent children • Mode of transmission
• Growth in cavities or cysts without invasion –– Inhalation of spores from bird excreta or
• Underlying cystic fibrosis and TB contaminated soil
• Allergic bronchopulmonary aspergillosis: – – No person-to-person transmission
Hypersensitivity
328 M. B. Laurens
Clinical presentation • Culture and DNA probe is the most definitive

• Flu-like symptoms method for the diagnosis
• Pulmonary infiltrates • High index of suspicion is important in patient
• Hilar lymphadenopathy with or without who travelled or underlying medical
calcifications conditions
• Erythema nodosum • Elevated erythrocyte sedimentation rate (ESR)
• In younger children may develop progressive • Lymphocytosis and monocytosis
disseminated histoplasmosis • Eosinophilia > 5%
• Chest radiograph may show consolidations
Treatment and hilar lymphadenopathy
• Not indicated for immunocompetent children
with mild/moderate disease Treatment
• Severe or disseminated infection, especially • Not indicated for immunocompetent children
in immunocompromised, treated with ampho- with mild/moderate disease
tericin B + steroids • Severe or disseminated infection, especially
in immunocompromised, treated with flucon-
azole or itraconazole
Coccidioides • High dose fluconazole for CNS infections
Coccidioidomycosis Blastomyces
• Blastomyces causes illness similar to
Background Histoplasma and Coccidioides
• Endemic areas • Seen in Arkansas and Wisconsin hunters and
–– California, Arizona, New Mexico, and loggers
Texas • Outbreak occurred in children visiting
• Mode of transmission Wisconsin lodge and beaver dam
–– Inhalation of airborne spores • Blastomyces may disseminate to the skin and
cause crusted skin lesions
• Bone lesions more common with
• Most cases are asymptomatic
blastomycosis
• Fever
• Itraconazole (mild disease) or amphotericin
• Cough
B (severe disease) are the treatments of
• Weight loss (common)
choice
• Fatigue
• Shortness of breath
Sporothrix schenckii
• Chills
• Common in florists, as thorny plants are
• Erythema nodosum
implicated
• Night sweats
• Symptoms appear from 7 to 30 days after
• Mild respiratory distress or respiratory failure
inoculation
in severe cases
• Present with painless papule at the site of
Diagnosis inoculation, then ulcerates
• Serology: The appearance of IgM or precipi- • Secondary lesions follow along the lymphatic
tin antibody against Coccidioides is the most chain proximally
sensitive serologic indication of early • Extracutaneous manifestation may occur,
infection especially in immunocompromised
• Treat with itraconazole for 2–4 weeks
PROTOZOA • Mode of transmission

–– Fecal–oral route
Giardia lamblia –– Travel to high-risk areas with poor sanita-
tion and hygiene
Giardiasis
Background • Can be asymptomatic
• Giardiasis is an infection of the small intes- • Amebic dysentery or colitis
tine caused by the flagellated protozoan –– Bloody diarrhea with mucus
Giardia intestinalis –– Tenesmus
• Mode of transmission • Hepatic abscess
–– Travelers and hikers who drink water con- –– Fever
taminated with stool from infected animals –– Abdominal pain
such as beavers, muskrats, and sheep –– Tender enlarged liver
–– Outbreaks also may occur from sewage –– Elevated liver enzymes
contamination of water supplies –– Elevated ESR
–– Unprotected anal sex also is a source of
transmission Diagnosis
–– Childcare centers from fecal–oral • Serum antibody (95% detectable in invasive
transmission amebiasis)
–– Food-associated outbreaks may occur • Stool microscopic examination
• Stool antigen
Clinical presentation • Ultrasound if liver abscess is suspected
• Most infections remain asymptomatic
• Watery diarrhea with abdominal cramping Treatment
• Nausea • Symptomatic cases with systemic symptoms
• Vomiting –– Metronidazole followed by paromomycin
• Weight loss or iodoquinol to eradicate colonization
• Flatulence • Asymptomatic amebiasis in nonendemic
areas should be treated with a luminal agent
Diagnosed (iodoquinol, paromomycin, or diloxanide
• Microscopic examination of the stool for furoate) to eradicate infection
cysts or by antigen detection • Amebic liver abscess cured by medical ther-
apy without drainage
Treatment
• Indicated for all symptomatic patients
• Metronidazole, a single dose of tinidazole, or Cryptosporidiosis
nitazoxanide for 3 days
• Immunocompromised patients at increased risk Background
for chronic giardiasis and treatment failure • Cryptosporidiosis, caused by
Cryptosporidium protozoa
• Transmitted via fecal–oral route; childcare
Entamoeba histolytica centers and swimming pools

• Amebiasis is caused by pathogenic species of • Nonbloody, watery diarrhea
Entamoeba • Chronic diarrhea in immunodeficient patients
330 M. B. Laurens
• Test using DFA in stool; routine ova and par- Treatment

asite testing insufficient • Infants with congenital toxoplasmosis:
Pyrimethamine plus sulfadiazine and folic
Treatment acid
• Many immunocompetent patients who have • Pregnant females: Spiramycin
cryptosporidiosis have self-limited disease
and do not require therapy
• A 3-day course of nitazoxanide: Pneumocystis jiroveci
–– To reduce duration and transmission of
diarrhea in children older than 1 year of Pneumocystis Pneumonia
age
• No swimming pool for at least 2 weeks after Background
diarrhea ends • Unicellular fungi that do not respond to anti-
fungal treatment
• Mode of transmission is unknown
Toxoplasma gondii • Commonly seen in immunocompromised
patients, e.g., HIV patients
Toxoplasmosis
Background • Subacute diffuse pneumonitis
• Obligate intracellular protozoa • Dyspnea
• Mode of transmission • Tachycardia
–– Ingestion of contaminated raw or uncooked • Hypoxemia that is exaggerated with exertion
meat • Nonproductive cough
–– Cat excreta • Fever
–– Organ transplants
–– Transplacental to fetus causes congenital Diagnosis
toxoplasmosis (see Chap. 2 “Neonatology”) • Chest radiography
–– Bilateral diffuse interstitial disease
Clinical presentation • Low CD4
• Most cases are asymptomatic • BAL
• Fever • Lung biopsy
• Malaise
• Rash Treatment
• Myalgia • TMP-SMX
• Cervical lymphadenopathy (most common • IV pentamidine in severe cases
sign) • Prophylaxis in immunocompromised patients
• Brain abscess (test for HIV) –– TMP-SMX
• Chorioretinitis usually present years later
(mostly congenital)
Plasmodium
Diagnosis
• Head CT: Ring-enhanced lesion, intracere- Malaria
bral calcifications
Background
• Toxoplasma IgM antibodies
• Intracellular protozoa
• PCR
• Transmitted by mosquito bites in endemic
areas of the tropics
Plasmodium falciparum • Vomiting and diarrhea

• Most severe, causing death within 48 h if • In severe cases
untreated –– Altered mental status
• Symptoms develop 10 days after mosquito –– Hepatosplenomegaly
bite, longer if taking prophylaxis –– Anemia
• Complications –– Thrombocytopenia
–– Cerebral malaria –– Hypotension
–– Pulmonary edema –– Hypoglycemia
–– Severe anemia –– Hyperkalemia
–– Renal failure –– Respiratory distress
–– Shock
• Treatment Diagnosis
–– Chloroquine sensitive (rare) • Rapid diagnostic test (immunochromato-
◦◦ Chloroquine graphic test)
–– Chloroquine resistant • Thick blood smear
◦◦ Artemether–lumefantrine • PCR available, but results are delayed
◦◦ Quinine plus doxycycline or
clindamycin Prevention
◦◦ Atovaquone–proguanil • Traveling to chloroquine resistant areas, e.g.,
–– Severe cases most tropical areas with malaria
◦◦ IV artesunate (available from Centers –– Atovaquone–proguanil 1–2 days before
for Disease Control and Prevention and 7 days after travel, or
[CDC] only; not yet FDA-approved) –– Doxycycline (> 8 years old) 1 week before
◦◦ Quinidine gluconate IV (no longer pro- until 4 weeks after travel
duced for the US market as of 2019) • Traveling to chloroquine sensitive areas, e.g.,
plus doxycycline or clindamycin Central America
–– Chloroquine 1–2 weeks before and 4 weeks
P. malariae, P. vivax, and P. ovale after, or
• Periodicity of symptoms – – Atovaquone–proguanil 1–2 days before
• Nephrotic syndrome – P. malariae (most and 7 days after travel
benign form)
• Hypersplenism and splenic rupture –
P. vivax and P. ovale HELMINTHIC ORGANISM
• Treatment
–– Chloroquine plus primaquine for Enterobius vermicularis
P. vivax, and P. ovale
–– Chloroquine for P. malariae Pinworm
Clinical presentation of malaria Mode of transmission

• History of traveling to endemic area • Person-to-person via fecal–oral route
• Paroxysmal fever, sweat, and rigors • Eggs survive up to 3 weeks and are ingested
• Pallor and jaundice from finger nails, bedding, and toys
• Headache and myalgia • Autoinfection
• Abdominal pain
332 M. B. Laurens
Clinical presentation Necator americanus

• Anal and vulvar itching (more at night)
• Enuresis Ancylostoma duodenale
Diagnosis Hookworm
• Visualizing the adult worm at night on the
perineum Background
• Transparent tape collected over three consec- • Found in rural, tropical, and subtropical
utive mornings under microscope low power locales
• Mode of transmission
Treatment –– Skin penetration of larvae from soil con-
• Pyrantel pamoate (over-the-counter), alben- taminated by human feces
dazole, mebendazole –– Ingestion
Clinical presentation (blood sucker worms from

Ascaris lumbricoides the intestine)
• Itchiness and burning sensation
Ascariasis • Pharyngitis and gastroenteritis
• Failure to thrive
Mode of transmission
• Short stature
• Ingestion of eggs from contaminated soil
• Anemia due to chronic blood loss
(fecal–oral)
Diagnosis
• Visualization of eggs in stool (may take
• Most patients are asymptomatic
5–10 weeks after infection)
• Nonspecific abdominal pain or discomfort
• Intestinal obstruction (large number of Treatment
worms) • Pyrantel pamoate (over-the-counter), alben-
• Due to larvae migration to the liver and lung: dazole, mebendazole
–– Obstructive jaundice
–– Peritonitis
–– Cough (Loeffler syndrome) Trichuriasis
Diagnosis Whipworm
• Seeing the ova on microscopic stool • Due to infection of large intestine with
examination Trichuris trichiura
• Seeing the adult worm itself • More common in the Southern United States
• Transmitted to humans by ingesting eggs
Treatment • Usually asymptomatic if only few worms
• Pyrantel pamoate (over-the-counter), alben- • Can cause fever, abdominal pain, weight loss,
dazole, mebendazole blood in stool, and rectal prolapse
• Presence of eggs in stool is diagnostic
• Treatment is with albendazole, mebendazole,
or ivermectin
Trichinella spiralis • In humans larvae do not develop into adult

worms but rather migrate through the host tis-
Trichinellosis sue, causing eosinophilia
• T. spiralis is usually found in pork • Treatment: Albendazole or mebendazole
• Symptoms depend on the worm location
• After ingestion the eggs hatch, larvae invade
the duodenum and cause abdominal Cestodes (Platyhelminthes)
symptoms
• Larvae penetrate, reach bloodstream, end in • Platyhelminthes include cestodes (tape-
muscular tissue and cause muscle pain worms) and trematodes (flukes)
• If the larvae reach the heart, can cause • Cestodes are flatworms (tapeworms)
myocarditis • The pork tapeworm Taenia solium, present in
• Ocular involvement: Presence of chemosis, two different ways
periorbital edema, and eosinophilia usually –– If the cysticerci are ingested, taeniasis
suggest the diagnosis develops and tape worm grows in the
• Diagnosis is confirmed by rising titers intestine
• Treatment is with albendazole or –– If contaminated food with eggs is ingested,
mebendazole the patient will develop cysticercosis
• Cysticerci live in CNS and the eyes and do
nothing until they die
Strongyloides stercoralis • Diagnosis of neurocysticercosis must be
considered in patients with new onset sei-
Strongyloidiasis zures and history of traveling to or immigra-
• S. stercoralis is common in certain areas tion from Mexico, Central, or South
(Kentucky and Tennessee) of the USA America, or who are from a household in
• The only helminthic organism that replicates these areas
in the body with autoinfection, and the infec- • Treatment: Albendazole or praziquantel
tion may persist for decades
• Can cause pulmonary symptoms with eosino-
philia and GI symptoms Trematodes (Platyhelminthes)
• Potentially fatal in immunosuppressed
patients • Trematodes or flukes
• Diagnosis of serial stool studies for larvae not • Clonorchis sinensis is the Chinese liver fluke
the eggs • Schistosoma haematobium infects the blad-
• Treatment: Ivermectin or albendazole der and causes urinary symptoms
• Schistosoma mansoni is a fluke found in
Africa, the Middle East, and South America
Toxocariasis • Schistosoma japonicum is found in Asia
• Most serious complications of Schistoso
• Toxocara canis and Toxocara cati can cause miasis is cirrhosis with esophageal varices
visceral larva migrans • Treatment: Praziquantel
• Transmitted to humans by ingesting soil con-
taminated with dog or cat excreta
334 M. B. Laurens
FEVER Fever in 1–3-Month-Old Infants
Fever Without Focus Background

• Large majority of children with fever without
Febrile Neonate localizing signs in 1–3 months age group
likely viral syndrome
Background • Most viral diseases have distinct seasonal
• Difficult to distinguish between a serious pattern, unlike bacteria, e.g., respiratory syn-
bacterial infection and self-limited viral ill- cytial virus, and influenza more common dur-
ness in this age group ing winter and enterovirus infection more
• Neonates who have fever and do not appear common during summer and fall
ill have a 7% risk of having a serious bacterial Management
infection • Ill-appearing (toxic) febrile infants
• Serious bacterial infections include occult ≤ 3 months:
bacteremia, meningitis, pneumonia, osteo- –– Require prompt hospitalization, immediate
myelitis, septic arthritis, enteritis, and UTI parenteral antibiotics after blood and CSF
• Late onset neonatal bacterial diseases, e.g., cultures are obtained
group B Streptococci, E. coli, and Listeria • Well-appearing infants 1–3 months previ-
monocytogenes and perinatal herpes (HSV) ously healthy with no evidence of focus of
infection infection:
• If the neonate has fever recorded at home by –– WBCs count of 5000–15,000 cells/μL, an
reliable parents, the patient should be treated absolute band count of ≤ 1500 cells/μL,
as febrile neonate normal urinalysis, and negative culture
• If excessive clothing and blanket falsely ele- (blood and urine) results are unlikely to
vate the temperature, the excessive covering have a serious bacterial infection
should be removed and retake the tempera- • The decision to obtain CSF studies in the
ture in 15–30 min well-appearing 1–3 months old infant depends
on the decision to administer empiric
Management antibiotics
• All febrile neonates must be hospitalized • If close observation without antibiotics
• Full sepsis evaluation including blood, urine; planned, a lumbar puncture may be deferred
CSF should be cultured
• CSF studies should include cell count, glu- F ever in 3–36 Months of Age
cose, and protein level, Gram stain, cultures;
HSV, and enterovirus PCR should be Background
considered • Approximately 30% of febrile children in the
• Blood and urine cultures warranted 3–36 months age group have no localizing
• Chest radiograph may be included signs of infection
• Child should receive empiric antibiotics such • Viral infections cause most fevers in this
as cefotaxime or gentamicin + ampicillin population
• Acyclovir should be included if HSV infec- • Risk factors indicating probability of occult
tion is suspected bacteremia: Temperature ≥ 39 °C, WBC
count ≥ 15,000/μL, elevated absolute neutro-
phil count, bands, ESR and C-reactive protein Table 9.4 Differential diagnosis of fever of unknown
(CRP) origin
• The risk of bacteremia and/or pneumonia or Fever type Differential diagnosis
pyelonephritis among infants 3–36 months of Infectious Viral: EBV, CMV, hepatitis, HIV,
parvovirus B19
age increases as temperature (especially Bacterial: tuberculosis, cat scratch,
> 40 °C) and WBC count (especially Brucella, Salmonella,
> 25,000) increase meningococcemia
Common: otitis media, sinusitis,
Management pneumonia, UTI, osteomyelitis, septic
• Toxic-appearing febrile children 3–36 months arthritis, meningitis
Less common: malaria, Lyme disease,
of age who do not have focal infection should endocarditis
be hospitalized, with prompt institution of Rheumatologic Juvenile idiopathic arthritis, SLE,
parenteral antibiotics after blood, urine, and dermatomyositis
CSF cultures are obtained (full sepsis Oncologic Leukemia, lymphoma, neuroblastoma,
evaluation) Ewing sarcoma, hemophagocytic
lymphohistiocytosis
• For nontoxic-appearing infants who have Autoimmune Inflammatory bowel disease,
temperature < 39 °C: Can be observed as out- macrophage activation syndrome
patient with no diagnostic test or antibiotics Drug related Penicillin, cephalosporins,
• For nontoxic infants who have rectal temper- sulfonamides, acetaminophen
ature ≥ 39 °C, options include obtaining a Other Kawasaki disease, thyrotoxicosis,
factitious fever
blood culture and administering empiric anti- EBV Epstein-Barr virus, CMV cytomegalovirus, UTI urinary tract
biotic therapy (ceftriaxone, a single dose infection, SLE Systemic lupus erythematosus
50 mg/kg not to exceed 1 g); or blood culture
with no antibiotic and observing the patient Approach
within 24 h as outpatient. (Careful observa- • Age of the patient is helpful:
tion without empiric antibiotics is generally –– Children > 6 years of age often have respi-
prudent) ratory or genitourinary tract infection,
localized infection (abscess, osteomyeli-
Fever of Unknown Origin (FUO)
tis), JIA, or (rarely) leukemia
Background –– Adolescent patients more likely to have
• FUO was defined as: TB, inflammatory bowel disease, autoim-
–– More than 8 days’ duration of illness. mune process, or lymphoma in addition to
Temperature greater than 38.3 °C (101 °F) the causes of FUO in younger children
on several occasions • Exposure to wild or domestic animals, and
–– Failure to reach a diagnosis despite 1 week zoonotic infection
of investigation • History of pica should be elicited; ingestion
• Patients with undiagnosed FUO (5–15% of of dirt is particularly important due to infec-
cases) generally have a benign long-term tion with T. canis or T. gondii
course, especially when the fever is not • Physical examination is essential to find any
accompanied by substantial weight loss or physical clues to underlying diagnosis, e.g.,
other signs of a serious underlying disease lymphadenopathy, rash, joint swelling, etc.
• FUO lasting > 6 months is uncommon in chil- • Laboratory determined on case-by-case basis
dren and suggests granulomatous or autoim- • ESR > 30 mm/h indicates inflammation and
mune disease (Table 9.4) needs further evaluation
336 M. B. Laurens
• ESR > 100

mm/h suggests tuberculosis, • California encephalitis viruses cause the
Kawasaki disease, malignancy or autoim- greatest proportion of symptomatic pediatric
mune disease infections
• Low ESR does not eliminate the possibility • Eastern equine encephalitis has the highest
of infection overall mortality rate
• CRP is another acute phase reactant that is • The importance of local epidemiological infor-
elevated and returns to normal more rapidly mation and seasonality cannot be ignored
than ESR • Enteroviruses are most often seen in spring
• Cultures, serologic studies, imaging studies, and summer; arthropod-borne illnesses in the
and biopsies, depending on the individual summer and fall
case
Treatment • Altered mental status
• The ultimate treatment of FUO is tailored to • Seizures
the underlying diagnosis • Weakness
• Empiric trials of antimicrobial agents may be • Sensory disturbances
dangerous and obscure the diagnosis of infec- • Nonepileptic movement disorders
tive endocarditis, meningitis, parameningeal • Young children in absence of identifiable
infection, and osteomyelitis cause may present with:
• Antipyretics for fever and relief of –– Somnolence
symptoms –– Disinterest in feeding
–– Weak suck and irritability
–– Loss of head control
ENTRAL NERVOUS SYSTEM
C –– Abnormal eye movements
(CNS) INFECTIONS • Further clinical clues:
–– Fever (either acutely or in the 1–4 weeks
Encephalitis interval before the onset of symptoms)
–– Meningeal irritation
–– Any child presenting with uncharacteristic
Definition behavior that is persistent and dispropor-
• Inflammation of the brain tionate to environmental and situational
factors
Causes
• Viral, e.g., West Nile virus and herpesvirus Initial evaluation of the patient includes
(most common) • Seasonal presentation
• Bacteria, e.g., mycoplasma, tertiary syphilis • History of immunosuppression
• Noninfectious, e.g., autoimmune • Travel history
• Prion protein • Recent local epidemiological information
• Parasitic • Presence of focal neurologic symptoms or
• Fungal deficits.
• Acute cerebellar ataxia
–– Ataxia Investigation
–– Nystagmus • CBC
–– Cerebellar dysarthria • Complete metabolic panel
• Urinalysis
Epidemiology • MRI or CT scan for intracranial pressure
• WNV remains the most commonly encoun- (ICP)
tered arboviral encephalitis agent • Electroencephalogram (EEG)
• Enteroviral infections can produce a sepsis- M eningitis

like syndrome with more remarkable hemato-
logic abnormalities eonatal Streptococcal Meningitis
N
• Neonatal HSV infections sometimes produce
hepatic function abnormalities and dissemi- • Guillain–Barré syndrome remains the pre-
nated intravascular coagulation dominant neonatal meningitis pathogen
• Syndrome of inappropriate antidiuretic hor- • Early-onset disease: Infants typically manifest
mone secretion (SIADH) with signs suggestive of sepsis, often with pneu-
• Lumbar puncture if normal pressure monia, but less commonly with meningitis
• Cerebrospinal spinal fluid study: • Late-onset disease: Infants typically are
–– The lumbar puncture is the single most uti- 3–4 weeks of age and present with meningitis
lized test for the diagnosis of encephalitis or bacteremia
–– Increased opening pressure
–– Normal or elevated protein concentration Neonatal Gram-negative meningitis
–– Normal glucose level • Gram-negative bacillary meningitis is rare, E.
–– Pleocytosis, polymorphonuclear leuko- coli being the most commonly isolated
cytes; then converts to lymphocytic in pathogen
many viral cases • Other Gram-negative neonatal meningitis patho-
–– Monocytic; predominance may show with gens such as Citrobacter koseri, Enterobacter
progression of the disease sakazakii, and Serratia marcescens
–– Hemorrhagic pleocytosis with HSV
Neonatal herpes simplex (HSV) infection
–– Atypical lymphocytes with EBV
• HSV in the newborn can present as isolated
–– Mononuclear leukocytes with echovirus or
skin or mucous membrane lesions, encephali-
varicella-zoster infection
tis, or disseminated process
–– PCR amplification of viral DNA
• HSV infection occurs most commonly in
–– Pleocytosis tends to be less dramatic in
infants born to mothers who have active pri-
parainfectious encephalitis or acute cere-
mary infection
bellar ataxia
• Frequently no maternal history or clinical
–– Fourfold rise in titer, especially IgM,
evidence is available to alert the practitioner
against a suspected agent is most often
to this diagnosis
considered diagnostic
• The incubation period is 2 days to 2 weeks,
• IV acyclovir while waiting for lumbar punc-
and most infants who develop HSV CNS
ture, or while waiting for laboratory results,
infection are 2–3 weeks of age
including HSV PCR
• Intracranial hypertension conservative Neonatal meningitis due to Listeria
measures • Common sources:
–– Head elevation –– Unpasteurized milk
–– Hyperventilation –– Soft cheese
–– Fluid restriction –– Prepared ready-to-eat meats
–– Mannitol is used on a limited basis –– Undercooked poultry
–– Unwashed raw vegetables
Treatment of seizure
• Can precipitate abortion and preterm
• Benzodiazepines (midazolam, lorazepam,
delivery
diazepam) in the beginning followed by
• Septic appearance in the neonate is typical in
loading dose of fosphenytoin, or phenobar-
cases of early onset
bital II
• Papular truncal rash has been identified
338 M. B. Laurens
S. pneumoniae Physical examination

• Pneumococcus is the leading pathogen caus- • Altered levels of consciousness can present
ing bacterial meningitis in infants and young as irritability, somnolence, lethargy, or coma
children in developed countries • ICP include:
–– Papilledema
N. meningitidis –– Diplopia
• Meningococcal disease generally occurs in –– Unilateral or bilateral dilated pupils
otherwise healthy individuals and often has a –– Poorly reactive pupils
fulminant presentation with high fatality –– Bulging fontanelle in infants
rates –– Head circumference should always be
obtained, especially in those who have an
Aseptic meningitis open fontanelle
• Enterovirus is the most common etiology • Meningismus is suggestive of meningeal
• B. burgdorferi in mid-Atlantic states (Lyme) irritation
• Vasculitis in the setting of systemic lupus ery- • Kernig sign:
thematosus or Kawasaki disease. –– The patient lies supine and the thigh is
• Drug-induced such as ibuprofen, and IV flexed at a right angle to the trunk. If knee
immunoglobulin extension from this position elicits pain,
the Kernig sign is positive
Other causes of meningitis
• Brudzinski sign:
• M. tuberculosis
–– The patient lies supine and flexes his or her
• B. burgdorferi
neck
• R. rickettsii
–– A positive sign occurs if the patient also
Clinical manifestations reflexively flexes the lower extremities,
• Infants younger than 1 month of age who typically at the knees
have viral or bacterial meningitis • Absence of Kernig and Brudzinski signs does
–– Fever not exclude meningitis
–– Hypothermia • Exanthems typical for enterovirus, borrelio-
–– Lethargy sis (erythema migrans), and invasive menin-
–– Irritability gococcal or pneumococcal disease (petechiae
–– Poor feeding and purpura) may be present
• Signs and symptoms of increased ICP and
Diagnosis
meningeal inflammation
• All children who are suspected of having
–– Vomiting
meningitis should have their CSF examined
–– Apnea
unless lumbar puncture is contraindicated
–– Seizures can also occur
• Contraindications of lumbar puncture
• Older children and adolescents often
include:
experience
–– Focal neurologic deficits
–– Malaise
–– Signs of increased ICP
–– Myalgia
–– Uncorrected coagulopathy
–– Headache
–– Cardiopulmonary compromise
–– Photophobia
• CT scan is performed before lumbar puncture
–– Neck stiffness
if any sign of ICP present
–– Anorexia
• CSF findings in bacterial meningitis
–– Nausea
(Table 9.5)
Table 9.5 Cerebrospinal fluid analysis • Appropriate antimicrobials are required in

Type of bacterial meningitis, HSV encephalitis,
infection White blood cells Protein Glucose Lyme meningitis, tuberculous meningitis,
Bacterial > 1000/μL High Low (less and rickettsial infection; in all cases, timely
meningitis than half of
serum)
diagnosis and correct antimicrobial choice
Viral < 500/μL Normal Usually are critical
meningitis normal • If the practitioner cannot perform a lumbar
(viral) puncture or there are contraindications to
Tuberculosis < 500/μL Very Low (less CSF examination, a blood culture should be
(predominant high than half of
lymphocyte) serum)
obtained and antibiotics administered
promptly
–– Glucose concentration is usually less than Drug choice and duration
one half of the measured serum value • For infants
–– Protein value often is greater than 100 mg/dL –– Ampicillin (300 mg/kg/day divided every
–– WBC often greater than 1000/mcL, with a 6 h) and cefotaxime (300 mg/kg/day
predominance of polymorphonuclear divided every 6 h) is appropriate.
leukocytes Gentamicin can be used instead of
–– Gram stain is extremely helpful if positive cefotaxime
–– CSF culture remains the gold standard for –– Acyclovir (60 mg/kg/day divided every
diagnosing bacterial meningitis 8 h) should be added if HSV infection is a
• CSF finding viral meningitis concern
–– WBC count of 50–500/mcL –– Vancomycin (60 mg/kg/day given every
–– Neutrophil predominance is common early 6 h) should be added, if the Gram stain
in the course of infection, shifting to lym- suggests pneumococcus
phocytic predominance quickly during the • Children older than 1–2 months of age
illness –– Vancomycin (60 mg/kg/day divided every
–– Glucose and protein concentrations fre- 6 h) plus ceftriaxone (100 mg/kg/day given
quently are normal, although the protein in one dose or divided into two doses) or
value can be slightly elevated. Gram stain cefotaxime (200–300 mg/kg/day divided
is universally negative every 6 h) should be used for empiric
–– In cases of enteroviral meningitis, entero- coverage
viral PCR can confirm the diagnosis –– Once culture and susceptibility data are
• Tuberculous meningitis, epidemiologic clue, available, definitive therapy can be selected
high protein, and lymphocytosis • HSV meningitis
• SIADH and hyponatremia commonly occur –– Neonatal HSV CNS infection typically is
in bacterial meningitis treated with IV acyclovir (60 mg/kg/day
• Leukopenia, thrombocytopenia, and coagu- divided every 8 h) for 21 days
lopathy may be present in meningococcal and –– The dosing for non-neonates is 30 mg/kg/
rickettsial infections day divided every 8 h IV for 14–21 days
–– Follow-up CSF HSV DNA PCR should be
Management
evaluated at day 21 and the course of ther-
• Therapy should not be delayed if CNS infec-
apy extended if the result is still positive
tion is suspected
340 M. B. Laurens
Corticosteroids in bacterial meningitis • Penetrating skull injury, congenital head and

• Adjunctive treatment has reduced rates of neck lesions
mortality, severe hearing loss, and neurologic • Immunosuppression
sequelae, significantly in adults who have • Commonly identified microorganisms:
community-acquired bacterial meningitis Streptococci and Staphylococci
• For children beyond the neonatal age groups,
available data suggest that the use of adjunc- Clinical presentation
tive corticosteroids may be beneficial for Hib • Triad of fever, headache, and focal neurologic
meningitis and could be considered in cases deficit
of pneumococcal meningitis • Headache (most common)
• The dose of dexamethasone for bacterial –– May be throbbing
meningitis is 0.6 mg/kg/day divided into four –– Worsens with changes in posture or
doses and administered IV for 4 days. The Valsalva maneuver
first dose should be given before or concur- • Vomiting
rently with antibiotics • Drowsiness
• Confusion
Care of the child exposed to meningitis • Coma
• Meningococcal and Hib disease create an • Hemiparesis
increased risk for secondary infection in • Papilledema
contacts
• Rifampin generally is the drug of choice for Frontal lobe abscesses
chemoprophylaxis in children • Apathy, memory deficits
• Personality change
Prognosis for meningitis • Mental slowing
• Intellectual deficits (intelligence quotient
< 70), hydrocephalus, spasticity, blindness, Cerebellar abscesses
and severe hearing loss are the most common • Nystagmus
sequelae • Defective conjugate eye movements to that
• Hearing loss occurs in approximately 30% of side
patients, can be unilateral or bilateral, and is • Ataxia
more common in pneumococcal than menin- • Hypotonia
gococcal meningitis
Laboratory diagnosis
• Little in the laboratory investigation of
Brain Abscess patients who have brain abscesses is specific
to the diagnosis except for culture of the
Causes purulent material and antibiotic sensitivity of
• Chronic otitis media the responsible organism
• Paranasal sinus infection
• Otogenic infections, poor dental hygiene/ Neuroimaging
complications from dental procedures • CT scan of the brain
• Mastoiditis –– Ill-defined
• Metastatic spread, e.g., endocarditis –– Low-density change within the
• Right-to-left cardiac or pulmonary shunts, parenchyma
especially in the presence of cyanotic con- – – Enhancement occurs following administra-
genital heart disease tion of contrast material
• Neurosurgical procedures (VP shunt)
–– Classic ring-enhancing lesion with sur- • For children with multiple ulcerations of buc-
rounding edema cal mucosa and conjunctival involvement
–– Calcification is common in abscesses in (mucous membranes) with skin rash, think
neonates erythema multiforme major (Stevens–
• MRI Johnson syndrome).
• For children with ulcerations of posterior
Antimicrobial therapy pharynx and painful papules on palms and
• For abscesses arising as a result of sinusitis in soles, think enterovirus (especially Coxsackie
which Streptococci are the most likely organ- virus) causing hand, foot, and mouth disease
isms, penicillin or cefotaxime and • For a child with pharyngitis and redness of
metronidazole skin creases of anterior cubital fossae (Pastia
• Chronic otitis media or mastoiditis often is lines, also called Thompson sign), think
associated with P. aeruginosa and Group A Strep (strep throat).
Enterobacteriaceae, antibiotics to treat • Egg allergy, including anaphylaxis, is not a
abscesses secondary to these infections contraindication to influenza vaccination. Only
should include penicillin, metronidazole, and persons with a previous severe allergic reaction
a third-generation cephalosporin to flu vaccine should not receive flu vaccine.
• Metastatic abscesses require a regimen based • For returning travelers with fever, obtain
on the likely site of primary infection malaria testing immediately and begin appro-
• S. aureus is commonly isolated in abscess priate therapy (artemether–lumefantrine or
following trauma atovaquone–proguanil for P. falciparum) if
positive. Do not delay!
Surgical intervention • Children < 2 years old can be colonized with
• Provide a specimen of purulent material for C. difficile and may test positive for the organ-
bacteriologic analysis and antibiotic sensitiv- ism. Only patients with C. difficile toxin pro-
ity testing duction should be considered for treatment
• Remove purulent material, thereby lowering with first-line oral metronidazole.
ICP and decreasing the mass effect of the • Patients with a classic bull’s eye rash at the
abscess site of a tick bite do not require diagnostic
• Decompress and irrigate the ventricular sys- testing. Treat for early localized Lyme dis-
tem and debride the abscess in the event of its ease with doxycycline (amoxicillin or cefu-
rupture into the ventricular system roxime for children < 8 years old).
• A positive blood culture for Candida should be
Prognosis
acted upon, including repeat blood culture and
• Brain abscess is a destructive lesion
IV antifungal therapy with central line removal
• Neurologic sequelae: Epilepsy, motor defi-
(if associated). A positive sputum culture for
cits, visual field cuts, learning disability,
Candida may represent colonization and
hydrocephalus requiring VP shunt placement
should be taken in the clinical context.
• Rash that begins on wrists and ankles, spread-
ing centrally to palms/soles, is likely Rocky
PEARLS AND PITFALLS Mountain spotted fever. Treat with doxycy-
cline no matter what age.
• Monospot testing for acute mononucleosis is • Children who return from travel to the Middle
not indicated for children < 5 years of age East or Central America with ulcerative skin
because results are not reliable in young lesions and no systemic symptoms may have
children. cutaneous Leishmaniasis.
342 M. B. Laurens
• Kingella kingae is an etiologic agent of indo- Suggested Reading

lent septic arthritis or osteomyelitis in a young
child. Can also cause bacteremia in infants American Academy of Pediatrics. Bartonella
and endocarditis in older children. henselae (cat-scratch disease). In: Kimberlin
• Uncommon causes of fever in pediatrics DW, Brady MT, Jackson MA, Long SS, editors.
include osteomyelitis, intraabdominal Red book: 2018–2021 report of the committee
abscess, deep venous thrombosis, Still dis- on infectious diseases. 31st ed. Itasca: American
ease, recurrent fever syndromes (periodic Academy of Pediatrics; 2018a. p. 244–7.
fever, aphthous stomatitis, pharyngitis and American Academy of Pediatrics. Chlamydial
adenitis (PFAPA), and familial Mediterranean infections. In: Kimberlin DW, Brady MT,
fever). Jackson MA, Long SS, editors. Red book: 2018–
• CNS complications of HIV include infection 2021 report of the committee on infectious dis-
(cryptococcal meningitis, toxoplasmosis, eases. 31st ed. Itasca: American Academy of
CMV encephalitis, neurocysticercosis), lym- Pediatrics; 2018b. p. 273–83.
phoma, progressive multifocal leukoencepha- American Academy of Pediatrics. Cytomegalovirus
lopathy (PML), peripheral neuropathy, and infection, varicella-zoster virus infections. In:
HIV encephalopathy. Kimberlin DW, Brady MT, Jackson MA, Long
• Nontuberculous mycobacteria can cause uni- SS, editors. Red book: 2018–2021 report of
lateral submandibular lymphadenitis with a the committee on infectious diseases. 31st ed.
violaceous hue in young children. Primary Itasca: American Academy of Pediatrics; 2018c.
treatment is surgical excision, not antibiotics. p. 310–7. and 869–83.
Excision prevents fistula formation. American Academy of Pediatrics. Gonococcal
• Most mild community-acquired pneumonia infections. In: Kimberlin DW, Brady MT,
can be treated as outpatient with oral amoxi- Jackson MA, Long SS, editors. Red book: 2018–
cillin as first-line therapy in patients who can 2021 report of the committee on infectious dis-
tolerate oral fluids. eases. 31st ed. Itasca: American Academy of
• The most common etiology for osteomyelitis Pediatrics; 2018d. p. 355–65.
and septic arthritis is S. aureus. Persons with American Academy of Pediatrics. Group A strep-
sickle cell disease are at higher risk for tococcal infections. In: Kimberlin DW, Brady
Salmonella. MT, Jackson MA, Long SS, editors. Red book:
• For post-exposure rabies prophylaxis, admin- 2018–2021 report of the committee on infectious
ister rabies immune globulin at the bite site diseases. 31st ed. Itasca: American Academy of
and rabies vaccine at a contralateral site on Pediatrics; 2018e. p. 616–28.
days 0, 3, 7, and 14 (four total doses of vac- American Academy of Pediatrics. Human immu-
cine). For immunocompromised persons nodeficiency virus infection. In: Kimberlin DW,
(HIV), a fifth dose of rabies vaccine is given Brady MT, Jackson MA, Long SS, editors. Red
on day 28. book: 2018–2021 report of the committee on
• To avoid botulism in the 1st year of life, infectious diseases. 31st ed. Itasca: American
avoid giving infants prepared cereals that Academy of Pediatrics; 2018f. p. 459–76.
contain honey, as these may also be a poten- American Academy of Pediatrics. Tuberculosis.
tial source. In: Kimberlin DW, Brady MT, Jackson MA,
• For TB testing, can use an interferon gamma Long SS, editors. Red book: 2018–2021 report
release assay (IGRA) for children > 2 years of the committee on infectious diseases. 31st
of age. Use skin testing for younger ed. Itasca: American Academy of Pediatrics;
children. 2018g. p. 829–53.
American Academy of Pediatrics Committee Duong M, Markwell S, Peter J, Barenkamp

on Pediatric AIDS. HIV testing and pro- S. Randomized, controlled trial of antibiotics in
phylaxis to prevent mother-to-child trans- the management of community-acquired skin
mission in the United States. Pediatrics. abscesses in the pediatric patient. Ann Emerg
2008;122(5):1127–34. Med. 2010;55(5):401–7.
American Academy of Pediatrics, American Public Fatahzadeh M, Schwartz RA. Human herpes
Health Association, National Resource Center simplex virus infections: epidemiology, patho-
for Health and Safety in Child Care and Early genesis, symptomatology, diagnosis, and man-
Education. CFOC standards online database. agement. J Am Acad Dermatol. 2007;57(5):
www.nrckids.org/CFOC. Aurora: National 737–63.
Resource Center for Health and Safety in Child Khazaeni LM. Ocular complications of congenital
Care and Early Education; 2019. Accessed 31 infections. NeoReviews. 2017;18(2):e100–4.
Jan 2019. Ralston SL, Lieberthal AS, Meissner HC,
Amren DP, Anderson AS, Wannamaker LW. Alverson BK, et al. Clinical practice guideline:
Perianal cellulitis associated with group A strep- the diagnosis, management, and prevention
tococci. Am J Dis Child. 1966;112(6):546–52. of bronchiolitis. Pediatrics. 2014;134(5):21):
Chayavichitsilp P, Buckwalter JV, Krakowski AC, e1474–502.
Friedlander SF. Herpes simplex. Pediatr Rev.
2009;30(4):119–30.
Hematology/Oncology
10
Arpan A. Sinha, Scott Moerdler, Ellen Fraint, Adit Tal,
Nora E. Rahmani, and Kerry Morrone
RED BLOOD CELL DISORDERS Anemia of Newborn (Fig. 10.2) [1]
Anemias: Introduction • In utero hemoglobin increases with advanc-

ing gestational age
• Anemia is a reduction of red blood cell (RBC) • At term: Cord blood hemoglobin is ~16.8 g/dL
volume or hemoglobin concentration below • Hemoglobin values are lower in premature
normal, which leads to a decrease in the infants
capacity of blood to carry oxygen • Physiologic nadir: After birth, hemoglobin
• The body compensates by increasing cardiac starts decreasing and a nadir is reached at
output, increased 2,3-diphosphoglycerate 8–12 weeks in term infants (nadir hemoglo-
(DPG) in RBCs, oxygen dissociation curve bin ~9 to 11 g/dL) and earlier around 6 weeks
shift to right, increased erythropoietin (EPO) in premature infants (nadir hemoglobin ~7 to
• Bone marrow starts producing more 10 g/dL)
RBCs—reticulocytosis • Normal process
• Normal hemoglobin values vary with age, • Does not result in signs of illness and does
sex, race, and ethnicity not require any treatment
• Prevalence of anemia in different age groups • Related to increased tissue oxygenation expe-
(Fig. 10.1) rienced at birth, shortened RBC life span, and
low EPO levels.
• Transplacental hemorrhage: Bleeding from
fetal into the maternal circulation sometimes
can be severe and cause clinically apparent
anemia
• Diagnosis made by Kleihauer–Betke (KB)
A. A. Sinha
Jimmy Everest Center of Pediatric Hematology and Oncology,
test, which detects fetal cells in maternal
Department of Pediatrics, The University of Oklahoma Health blood, or flow cytometry
Sciences Center, Oklahoma City, OK, USA
S. Moerdler
Pediatric Hematology/Oncology Program, Department of
Pediatrics, Rutgers Cancer Institute of New Jersey, Robert Wood emolytic Disease of the Newborn
H
Johnson Medical School, Rutgers University, (Erythroblastosis)
New Brunswick, NJ, USA
E. Fraint · A. Tal · N. E. Rahmani ∙ K. Morrone (*)
Division of Pediatric Hematology, Oncology, Marrow and Blood
• Transplacental passage of maternal antibod-
Cell Transplantation, Department of Pediatrics, Children’s Hospital ies active against paternal RBC antigens of
at Montefiore, Bronx, NY, USA the infant
e-mail: kmorrone@montefiore.org

346 A. A. Sinha et al.
Fig. 10.1 Prevalence of

anemia in different age Hemolytic Iron Deficiency Iron Deficiency
groups
DIC Rh Especially in females
Hemolytic
Immunohemolytic ABO
Alpha chain defects Beta chain defects
Hemorrhage
Intrapartum
Feto -maternal
Hypoproliferative Hypoproliferative
Intrauterine
infection Maturation Abnormalities
Birth 3 months 6 months 3 years 10 years adult
Fig. 10.2 An approach Anemia in the newborn

to the diagnosis of infant
anemia in the newborn
infant. MCV mean
corpuscular volume, PK Reticulocyte
pyruvate kinase, G6PD count
glucose-6-phosphate
dehydrogenase, DIC Low Normal/high
disseminated
intravascular coagulation.
(Adapted from Kliegman Coombs
Congenital hypoplastic test
et al. [1], with anemias
permission)
Congenital infections
Coombs test Coombs test
Negative Positive
Immune hemolytic anemia

MCV
- ABO
- RH
Normocytic/ - Minor blood group
Microcytic Macrocytic mismatch
- Alpha thalassemia - Hereditary spherocytosis

syndromes - Hereditary elliptocytosis
- Chronic intrauterine - Stomatocytosis
blood loss
- Pyropoikilocytosis
- PK deficiency
- G6PD deficiency
- DIC
- Acute blood loss
- Infection
10 Hematology/Oncology 347
• Important cause of anemia and jaundice in • Indirect-reacting bilirubin content rises rap-
newborn infants idly to high levels in the first 6 h of life
• More than 60 different RBC antigens are
capable of eliciting an antibody response Antenatal diagnosis
• Significant disease is associated with the D • Antenatal diagnosis is very important
antigen of the Rh group and with ABO • Important history: History of previous trans-
incompatibility fusions, abortion, or pregnancy
• Hemolytic disease may be caused by other • Fetal Rh status should be determined, and
RBC antigens maternal titers should be monitored
Treatment
RH Incompatibility • Treatment of an unborn infant: Intravascular
(umbilical vein) transfusion of packed RBCs
Pathogenesis • Treatment of a liveborn infant: Blood transfu-
• Rh-negative mother develops antibodies by sion, intravenous immunoglobulin, exchange
Rh-positive blood from Rh-positive fetus transfusion
during pregnancy or delivery
• Initial rise in immunoglobulin M (IgM) and, Prevention of Rh sensitization
later, IgG, which can cross the placenta to • Prevent initial sensitization of Rh-negative
cause hemolytic manifestations mothers by Rho(D) immune globulin (human)
• Hemolytic disease rarely occurs during a first within 72 h of delivery of an Rh-positive
pregnancy but can be more severe in subse- infant, ectopic pregnancy, abdominal trauma
quent pregnancies in pregnancy, amniocentesis, chorionic villus
biopsy, or abortion
• Wide spectrum of hemolytic disease
• Jaundice evident within the first 6 h after birth ABO Incompatibility
• Ranges from mild hemolysis to severe
anemia Introduction
• Profound anemia, pallor, signs of cardiac • Most common cause of hemolytic disease of
decompensation, massive anasarca, and cir- the newborn, generally results in milder dis-
culatory collapse ease than Rh incompatibility
• Risk of bilirubin encephalopathy • Usually, the mother is type O and the infant is
• Hydrops fetalis type A or B
• Although ABO incompatibility occurs in
Laboratory 20–25% of pregnancies, hemolytic disease
• Anemia develops in only 10% of the offspring in such
• Direct antiglobulin test (DAT), or Coombs pregnancies
test, is positive
• Reticulocyte count is increased Clinical presentation
• The blood smear typically shows polychroma- • Most cases are mild, with jaundice being the
sia and a marked increase in nucleated RBCs only clinical manifestation, which usually
• White blood cell (WBC) count may be nor- appears during the 1st 24 h
mal or elevated; thrombocytopenia may • Hydrops fetalis is extremely rare
develop in severe cases • The liver and spleen are not greatly enlarged
• Rarely, it may be severe and symptoms and –– If bone marrow is overwhelmed, or anemia
signs of kernicterus develop rapidly is secondary to a primary bone marrow
(production) problem, then low/inadequate
Diagnosis reticulocyte count may be seen
• Presence of ABO incompatibility
• A weakly to moderately positive DAT
(Coombs test) result MICROCYTIC ANEMIA
• Spherocytes in the blood smear
• Indirect hyperbilirubinemia I ron-Deficiency Anemia (IDA)
• The hemoglobin is usually normal, but may
be as low as 10–12 g/dL • Most common type of anemia in infancy and
• Reticulocytosis with polychromasia and childhood
increased numbers of nucleated RBCs
• In 10–20% of affected infants, the unconju- Etiology
gated serum bilirubin level may reach 20 mg/ • Blood loss
dL or more unless phototherapy is –– Gastrointestinal (GI) bleed (ulcer, gastritis,
administered drug induced with NSAIDs, steroids, etc.)
–– Intravascular hemolysis and
Treatment hemoglobinuria
• Phototherapy –– Menstruation
• In severe cases, intravenous immunoglobulin –– GI lesions: Meckel diverticulum, vascular
(IVIG) administration can reduce the need malformations
for exchange transfusion –– Cow’s milk allergy
• Exchange transfusions may be needed in –– Goodpasture syndrome
some cases to correct dangerous degrees of –– Hemosiderosis
anemia or hyperbilirubinemia –– Parasitic infections
• Nutritional
Clinical approach to a child with anemia
–– High cow’s milk consumption (> 32 oz/
• Thorough history and physical exam
day)
• Initial laboratory testing should include
–– Malnutrition
hemoglobin (Hgb)/hematocrit (Hct), RBC
–– Insufficient intake (vegan or vegetarian,
indices, WBC count and differential, platelet
iron-poor diet)
count, reticulocyte count, and examination of
• Physiologic
the peripheral blood smear
–– Low birth weight
• Further systematic evaluation based on initial
–– Rapid growth
tests (follow flow chart below) (Fig. 10.3) [1]
–– Pregnancy
Key classification markers • Impaired absorption
• Size of RBC mean corpuscular volume –– Malabsorption syndrome (celiac disease,
(MCV) can be classified as inflammatory bowel disease [IBD])
–– Microcytic (MCV < 70 + age) – – Gastrectomy
–– Macrocytic (MCV > 100)
–– Normocytic (MCV > 70 + age and < 100)
• Weakness
• Reticulocyte count
• Fatigue
–– Reticulocytosis indicates bone marrow
• Difficulty concentrating
response to anemia
• Headaches
Evaluation of anemia
MCV
Microcytic Normocytic Macrocytic
Reticulocyte count
Reticulocyte count
Reticulocyte count
Low/Inadequate High
Low/Inadequate High Low/Inadequate High

– Thalassemia
syndromes - Acute bleeding - Antibody mediated - Active hemolysis
– Hemoglobin C and hemolysis - Folate deficiency
- Anemia of chronic with very elevated
E disorders - Vitamin B12 reticulocyte count
inflammation - Microangiopathies deficiency (reticulocytes are
– Pyropoikilocytosis (HUS, TTP, DIC,
- RBC aplasia - Congenital macrocytic)
(TEC, infection, kasabach Merritt) aplastic anemia
drugs) (DBA, Fanconi - Some
- Membranopathies
anemia, Pearson dyserythropoietic
- Endocrinopathy (spherocytosis,
syndrome) anemias
elliptocytosis)
- Renal failure
- Acquired aplastic
- Hypersplenism - Enzymopathies
anemia
(G6PD, PK
deficiencies) - Hypothyroidism
- Drug induced
- Hemoglobinopathies
(HbSS, HbSC) - Trisomy 21
- Hypersplenism
Fig. 10.3 Approach to anemia in older children based on botic thrombocytopenic purpura, DIC disseminated intravas-
mean corpuscular volume. MCV mean corpuscular volume, cular coagulation, G6PD glucose-6-phosphate dehydrogenase,
RBC red blood cell, TEC transient erythroblastopenia of PK pyruvate kinase, DBA Diamond–Blackfan anemia.
childhood, HUS hemolytic uremic syndrome, TTP throm- (Adapted from Kliegman et al. [1], with permission)
• Pallor • RBCs become more microcytic and hypo-

• Pica chromic (Fig. 10.4)
• If severe (Hgb < 5 g/dL) • Increased poikilocytosis
–– Tachycardia, palpitations • Low MCV
–– Irritability • Increased red blood cell distribution width
–– Systolic murmur (RDW)
• Thrombocytosis (can reach up to 1 million/
Laboratory mm3)
• Low iron level • Mentzer index > 13 (MCV/RBCs)
• Low reticulocyte count
• Low ferritin (< 10 ug/L)—most sensitive and Treatment
specific test • Dietary change
• Low transferrin saturation –– Avoid excessive cow’s milk (less than 16
• High total iron-binding capacity (TIBC) ounces per day)
• Parenteral iron therapy

–– Circumvents absorption problems
–– Indications:
◦◦ Malabsorption
◦◦ IBD
◦◦ Chronic blood loss
◦◦ Chronic kidney disease
–– Increases hemoglobin levels more quickly
than oral iron
–– More expensive than oral therapy
–– Side effects include hypersensitivity reac-
tions, headache, flushing, nausea, back and
chest pain, arthralgia
Fig. 10.4 Peripheral blood smear example of hypochromic/ ◦◦ Resolves within 48 h
microcytic anemia. Notice the variability in the sizes of red • Blood transfusion
blood cells. The arrows point to hypochromic erythrocytes –– Appropriate for children with Hgb < 5 g/
with large central hollow. (Courtesy of M. Nawar Hakim, dL or with clinical signs and symptoms
MD, Department of Pathology, Texas Tech University Health
such as respiratory distress, lethargy, sig-
Sciences Center, El Paso, Texas)
nificant tachycardia
–– If Hgb < 5 g/dL, transfuse slowly and with
–– Iron-fortified formula and rice cereal in caution or avoid fluid overload or conges-
infants tive heart failure
–– Meat and other iron- and vitamin C-rich foods ◦◦ 5 ml/kg over 4 h
• Oral iron therapy—ferrous sulfate, gluconate,
fumarate
–– Convenient, inexpensive, and effective nemia of Chronic Disease
A
–– 3 to 6 mg/kg of elemental iron in two to
three divided doses daily • Associated with chronic inflammatory states
–– Continue for 3 months to replenish iron –– Pyogenic infections
stores –– Systemic diseases—HIV, malignancy
–– Improved absorption with vitamin C, worse –– Autoimmune diseases, e.g., systemic lupus
absorption with milk erythematosus, rheumatoid arthritis
–– Side effects include nausea, vomiting, con-
stipation, and metallic taste Etiology
–– Changes after treatment with oral iron: • Renal production of EPO suppressed by
◦◦ Within 12–24 h: Irritability decreases, inflammatory cytokines (IL-1, IL-6, TNF-
increased appetite alpha), resulting in decreased RBC production
◦◦ 36 to 48 h: Initial bone marrow response • Hepcidin, an acute phase reactant, decreases
with erythroid hyperplasia intestinal iron absorption and prevents release
◦◦ 48 to 72 h: Reticulocytosis, peaks at of iron from macrophages
5–7 days –– Lack of iron availability for developing
◦◦ 1 to 3 months: Repletion of stores RBCs
◦◦ Recheck hemoglobin 4 weeks after ini-
tiation of treatment Laboratory
▪▪ Hgb should rise at least 1 g/dL within • Usually normocytic and normochromic,
4 weeks rarely microcytic
• Anemia can be mild (Hgb 10–11 g/dL) or Alpha-Thalassemia Trait/Minor

severe (Hgb < 9 g/dL) • Deletion or dysfunction of two genes
• Low serum iron –– Heterozygosity (aa/--), more common in
• Low transferrin saturation Asian ancestry
• Elevated serum ferritin –– Homozygosity (a-/a-), more common in
• Normal-to-low TIBC African ancestry
• Mild hypochromic microcytic anemia
Treatment
• Correct the underlying disorder Laboratory
• Red blood cell transfusions or EPO may be • Mentzer index < 13
necessary in severe, symptomatic anemia • Hgb > 9 g/dL
• Normal Hgb electrophoresis or Hb Barts
(3–8%)
THALASSEMIAS • Diagnosed incidentally or misdiagnosed as IDA
Alpha-Thalassemia
Hemoglobin H Disease
• Healthy individuals have 4 alpha-globin • Deletion of three genes
genes, 2 on each chromosome 16 • Mild to moderate hypochromic microcytic
• Typically caused by gene deletions in one or anemia
more of these genes • Symptomatic at birth with mild anemia (Hgb
–– Alpha-globin production is reduced to 9–11 g/dL), neonatal jaundice
absent • Anemia exaggerated by infection, exposure
–– Severity of phenotype increases with loss to oxidizing drugs, pregnancy
of one, two, three, or four functioning • May develop splenomegaly, jaundice, and
alpha-globin alleles cholelithiasis
• Geographic regions: Southeast Asia, • Up to 30% HbH on electrophoresis
Mediterranean (more severe), Africa
• Diagnosis: Clinically or with alpha-globin Alpha-Thalassemia Major
chain analysis • Deletion of four genes
• Excess beta chains lead to beta 4 chains • Severe microcytic anemia with hydrops fetalis
(HbH) • Usually fatal in utero
• Excess gamma chains lead to a tetramer of • Hb Barts on electrophoresis, no HbF, HbA,
gamma-globin (Hb Barts) HbA2
–– Hb Barts cannot deliver oxygen to tissues
because of its affinity for oxygen is too high
Alpha-Thalassemia Syndromes
Beta-Thalassemia
Silent Carrier
• Deletion or dysfunction of one gene • Healthy individuals have 2 beta-globin genes,
• Asymptomatic 1 on each chromosome 11
• Normal complete blood count (CBC) • Beta-globin production is reduced to absent
• Normal Hgb electrophoresis • Multiple possible genetic mutations/
deletions
• Geographic regions: Southeast Asia, • Hypercoagulable state, extramedullary hema-

Mediterranean, Africa (milder) topoiesis, pulmonary hypertension
• Accumulation of excess alpha-globin chains • Usually does not require regular transfusions,
on the RBCs causes increased reactive oxy- but may require more transfusions over time
gen species and damage to cellular proteins
→ shortened RBC survival eta-Thalassemia Major (Cooley Anemia)
B
• Clinical manifestations caused by ineffective • Most severe form of beta-thalassemia and
erythropoiesis, chronic hemolytic anemia, presents at 6–12 months of age
and iron overload • Minimal to no beta-globin chain production,
• Diagnosed by hemoglobin electrophoresis or little to no HbA
beta-globin chain analysis • Caused by homozygosity or compound het-
erozygosity for β0 mutations or β+ variants
• Excess alpha-globin chains result in increased
Beta-Thalassemia Syndromes RBC destruction and ineffective erythropoiesis
Beta-Thalassemia Minor (Trait)
• Heterozygous β0 or β+ Laboratory
• Asymptomatic • Severe, transfusion-dependent microcytic
• May have microcytic anemia, hypochromia, hypochromic anemia
target cells on peripheral smear • Reticulocytopenia with elevated RBC count
• Hgb electrophoresis with slightly elevated • Nucleated RBCs
HgbA2 • Target cells on smear
• Elevated LDH, indirect bilirubin, low hapto-
globin—indicates hemolysis
Beta-Thalassemia Intermedia • Iron overload, elevated ferritin
• Variable symptoms, but more symptomatic • Hgb electrophoresis with elevated HgbA2
than minor and HbF
• Results from diverse genetic explanations
due to beta gene mutations Clinical presentation
• Pallor, jaundice, fatigue
Laboratory • Gallstones
• Hgb between 7 and 10 g/dL • Hepatosplenomegaly
• Smear shows microcytosis, hypochromia, tar- • May be less severe with increased HbF
get cells, and basophilic stippling • Extramedullary hematopoiesis—skeletal
• Hgb electrophoresis with elevated HgbA2 deformities
and HbF –– Maxillary hypoplasia, flat nasal bridge,
• Serum iron, ferritin, and transferrin saturation frontal bossing
may be increased –– Osteopenia/osteoporosis—pathologic
• Mentzer index < 13 bone fractures
• Endocrinopathies from iron overload
Clinical presentation –– Hypothyroidism
• Varied –– Hypoparathyroidism
• Can present with pallor, jaundice, anemia, –– Diabetes mellitus
splenomegaly, or skeletal deformities during –– Growth impairment
childhood or later –– Hypogonadism
• Cardiovascular from iron overload Sideroblastic Anemia

–– Congestive heart failure • Heritable or acquired erythropoietic disorders
–– Cardiac arrhythmias due to abnormalities in heme synthesis and
–– Pulmonary hypertension mitochondrial function
• Often associated with syndromes
Treatment • Variable severity of anemia
• Chronic hypertransfusion therapy once diag- • Presence of ringed sideroblasts (RBC precur-
nosis is confirmed sors with iron-containing granules) in bone
• Iron chelation therapy marrow aspirate [2]
–– Deferoxamine—parenteral agent • Anisocytosis, poikilocytosis, target cells,
–– Deferasirox and deferiprone (oral agent Pappenheimer bodies on blood smear
more tolerable) • May have microcytic anemia in the absence
• Monitoring with ferritin level, cardiac, and of iron deficiency or thalassemia, low reticu-
liver magnetic resonance imaging (MRI) for locyte count
iron load in critical organs • Splenectomy contraindicated for treatment
• Splenectomy may be indicated with severe
anemia and increase in transfusion require-
ments, growth retardation, hypersplenism METHEMOGLOBINEMIA
with other cytopenias, splenic infarction,
(CONGENITAL OR ACQUIRED)
splenic vein thrombosis, or symptomatic
• Allogeneic hematopoietic stem cell • Iron molecule in hemoglobin is oxidized from
transplant ferrous (Fe2+) to ferric (Fe3+) state, resulting
in methemoglobin (MHg), which cannot
transport oxygen
OTHER MICROCYTIC ANEMIAS • This leads to decreased oxygen-carrying
capacity of blood and cyanosis with signifi-
Lead Poisoning cant MHg levels
• Increase in MHg can be acquired (from expo-
• Young children (< 6 years) more susceptible sure to toxic substances) or congenital
to toxic effects of lead (absence of reductive pathways, e.g., NADH
• Typically, exposure is through ingestion or cytochrome b5 reductase deficiency)
inhalation (paint chips, water, pottery) • Acquired more common, with infants particu-
• Can lead to permanent neurocognitive defi- larly more vulnerable
cits, acute encephalopathy at extremely high • May be seen in infants who ingested foods
levels, chronic interstitial nephritis and water high in nitrates (well water), infants
• Anemia—lead inhibits heme synthesis and exposed to aniline teething gels or other
induces hemolysis chemicals, infants with severe gastroenteritis
• Elevated blood erythrocyte protoporphyrin or and acidosis
zinc protoporphyrin (heme precursors), high • MHg of 15% associated with visible cyano-
serum lead level sis, MHg of 70% is lethal
• Smear shows basophilic stippling of RBCs, • MHg colors the blood brown
ringed sideroblasts in bone marrow
Treatment
• IV methylene blue
MACROCYTIC ANEMIA Clinical presentation

• Clinical features associated with anemia
Folic Acid Deficiency • Irritability, chronic diarrhea, poor weight gain
• Hemorrhage from thrombocytopenia in
• Folic acid is necessary to form biologically severe cases
active folates
• Folates are essential for DNA replication and Laboratory
cellular proliferation • Macrocytic anemia (MCV > 100 fl)
• Humans cannot synthesize folate and depend • Variations in RBC shape and size
on dietary sources • Low reticulocyte count, nucleated RBCs
• Folate supplementation is recommended dur- • Megaloblastic changes, including hyperseg-
ing pregnancy to prevent neural tube defects mented neutrophils (> 5 lobes)
in fetus • Elevated LDH (marker of ineffective
erythropoiesis)
• Neutropenia and thrombocytopenia may be
Etiology present in severe deficiency
1. Inadequate intake • Hypercellular bone marrow with megaloblas-
• Especially during times of increased tic changes
requirement—seen in pregnancy, growth
spurts in children, and in chronic hemo- Treatment
lytic anemias • Rule out concomitant B12 deficiency before
• Malnutrition is the most common cause of starting folic acid therapy, as folic acid treat-
folate deficiency in older children ment can correct the anemia of B12 defi-
• Dietary sources include green vegetables, ciency; however, it can aggravate associated
fruits, and animal organs like liver and neurologic abnormalities
kidneys • Treat with folic acid at 0.5–1 mg/day oral/
• Body stores for folic acid are limited; parenteral for 3–4 weeks until a definite
2–3 months on folate-free diet hematologic response is seen followed by
• Goat’s milk is deficient, and supplementation maintenance dose therapy with a multivita-
must be given if goat’s milk is the main food min (containing 0.2 mg of folate) daily
• Powdered milk may also be a poor source • Hematologic response can occur within 72 h
of folic acid, unless supplemented (can be used as a diagnostic test as well, if
2. Decreased folic acid absorption diagnosis is unclear)
• Chronic diarrhea, removal of ileum or IBD,
celiac disease
• Certain anticonvulsant medication, e.g., Vitamin B12 Deficiency
phenytoin and primidone, can impair
absorption • Active metabolites of cobalamin (vitamin
3. Congenital abnormalities in folate trans- B12) are essential cofactors in two metabolic
port and metabolism reactions—methylation of homocysteine to
• Hereditary folate malabsorption methionine and conversion of methylmalonyl-
• Functional methionine synthase coenzyme A (CoA) to succinyl CoA. These
deficiency reactions are critical to DNA, RNA, and pro-
• Dihydrofolate reductase deficiency tein synthesis
4. Drug-induced abnormal metabolism • Cobalamin is synthesized exclusively by
• Methotrexate, pyrimethamine, trimethoprim microorganisms, and humans rely on dietary
sources (animal products, including meat, or anti-parietal cell antibodies. Can have
eggs, fish, and milk) for their needs associated immunologic abnormalities,
• Vitamin B12 stores last for 3–5 years candidiasis, hypoparathyroidism, other
• In young infants born to mothers with low endocrine deficiencies
vitamin B12 stores, clinical signs of cobala- 3. Absence of vitamin B12 transport protein
min deficiency can become apparent in the 4. Inborn errors of cobalamin metabolism
first 6–18 months of life
• May have nonspecific manifestations such as
Etiology weakness, fatigue, failure to thrive, and
1. Inadequate B12 intake irritability
• In infants, mostly nutritional due to • Can also have pallor, glossitis, vomiting, diar-
decreased vitamin B12 levels in breast rhea, and icterus
milk of B12-deficient mothers • Neurologic symptoms can include sensory
• In children and adults, strict vegetarian or and motor deficits, seizures, developmental
vegan diet delay, developmental regression, and neuro-
2. Impaired absorption psychiatric changes
• Secondary to gastric surgery or medications • Neurologic problems can occur in the absence
that impair gastric acid secretion may result of any hematologic abnormalities
in intrinsic factor (IF) deficiency, leading to
decreased vitamin B12 absorption Laboratory
• Pancreatic insufficiency • Macrocytic anemia (MCV > 100) (Fig. 10.5)
• History of neonatal necrotizing enterocoli- • Low reticulocyte count for degree of anemia
tis, IBD, celiac disease, or surgical removal • Megaloblastic changes, including hyperseg-
of the terminal ileum can result in impaired mented neutrophils (> 5 lobes)
absorption of vitamin B12
• Fish tapeworm Diphyllobothrium latum
infestation
• Hereditary intrinsic factor deficiency
(HIFD)—rare autosomal recessive disor-
der due to mutations in the IF gene, which
leads to lack of gastric IF or a functionally
abnormal IF
• Imerslund–Gräsbeck syndrome—rare,
autosomal recessive, clinically apparent by
age six
–– Selective vitamin B12 malabsorption in
the ileum, and consequent vitamin B12
deficiency
–– Presents with megaloblastic anemia,
possible neurologic defects and/or
proteinuria
–– Fatal if it remains untreated Fig. 10.5 Red cells are usually approximately the size of a
• Classic pernicious anemia (autoimmune small lymphocyte nucleus (arrow). In this case, the red cells
are slightly larger than the lymphocyte nucleus on average.
gastritis)—can rarely affect children dur-
Macrocytic anemia is most often a result of folate or vitamin
ing adolescence. Presence of IF antibodies B12 deficiency
• Elevated LDH Diamond–Blackfan Anemia

• Normal iron and folic acid levels (Congenital Hypoplastic Anemia)
• Increased methylmalonic acid and total
homocysteine levels Etiology
• Excessive excretion of methylmalonic acid in • Rare, congenital bone marrow failure
the urine is also a sensitive index of vitamin syndrome
B12 deficiency. Serum homocysteine, on the • 90% of cases are recognized in the first year
other hand, is also elevated in folate defi- of life
ciency, homocystinuria, and renal failure • Mostly autosomal dominant
• Anti-IF antibodies and anti-parietal cell anti- • Primary defect in the erythroid progenitors
bodies—useful for the diagnosis of perni-
cious anemia. Classic Schilling test is no Clinical presentation (Tables 10.1 and 10.2)
longer regarded as the diagnostic test • Profound anemia manifested by 2–6 months
of age
Treatment • More than 50% have associated congenital
• Initial correction with parenteral administra- anomalies
tion of vitamin B12. Goal is to correct defi- • Craniofacial abnormalities (hypertelorism,
ciency, consolidate response, replete stores, snub nose, and high arched palate) are most
and prevent relapse common—50% cases
• Treat underlying cause • Skeletal anomalies, mostly upper limb and
• Duration of treatment dependent on underly- hand (e.g., thumb abnormalities, absent radial
ing cause. May require lifelong supplementa- pulse—30% cases)
tion if underlying cause irreversible, e.g., • Short stature
pernicious anemia • Genitourinary, cardiac, ophthalmologic, and
musculoskeletal anomalies may also be seen
Pearson Marrow–Pancreas Laboratory

Syndrome • Macrocytic RBCs with no hypersegmenta-
tion of neutrophils
• A form of congenital hypoplastic anemia • Normal B12 and folate
• Signs of marrow failure in the neonatal period,
characterized by macrocytic anemia and, occa-
sionally, neutropenia and thrombocytopenia
• Fetal hemoglobin is elevated Table 10.1 Clinical findings of Fanconi anemia and
• Bone marrow shows vacuolated erythroblasts Diamond–Blackfan syndrome
and myeloblasts Fanconi anemia Diamond–Blackfan anemia
• Associated clinical features are failure to All bone marrow cells are Pure red cell aplasia
affected (aplastic anemia) (normal WBCs and
thrive, pancreatic fibrosis with insulin-depen- platelets)
dent diabetes, muscle and neurologic impair- Normal adenosine High adenosine deaminase
ment, early death deaminase enzyme (ADA) enzyme (ADA)
• Caused by mitochondrial DNA defect, vari- Macrocytic Macrocytic
able clinical course Elevated fetal hemoglobin Elevated fetal hemoglobin
(HbF) (HbF)
• Supportive care includes RBC transfusions as Thumb anomalies Thumb anomalies
needed for anemia and granulocyte-colony Short stature Short stature
stimulating factor (G- CSF) for severe Skin changes are common Not common
neutropenia WBC White blood cells
Table 10.2 Clinical findings of Diamond–Blackfan syn- Prognosis

drome and transient erythroblastopenia of childhood • Cancer predisposition syndrome
Transient • Increased risk for myelodysplastic syndromes
erythroblastopenia of (MDS), acute myeloid leukemia (AML),
childhood Diamond–Blackfan anemia
colon carcinoma, osteosarcoma, and female
Pure red cell aplasia Pure red cell aplasia
(acquired) (congenital) genital cancers
1–3 years of age (most 2–3 months of age • Survival around 75% at age 40
common)
Common Extremely rare
No congenital anomalies Thumb anomalies, SS,
craniofacial anomalies, Fanconi Anemia
urogenital anomalies
Normocytic (normal Macrocytic Genetics
MCV)
Normal fetal hemoglobin Elevated fetal hemoglobin
• Mostly autosomal recessive, rarely can be
(HbF) X-linked recessive
Normal serum iron High serum iron
Normal adenosine High adenosine deaminase Clinical presentation (Table 10.1)
deaminase enzyme enzyme (ADA) • Skin abnormalities ~55% of cases (most
(ADA)
Transfusion rarely Transfusion and steroids are
common)
required always required –– Hyperpigmentation of the trunk and inter-
MCV mean corpuscular volume, SS short stature triginous areas, café-au-lait spots, vitiligo
• Short stature ~50% of cases
• Increased adenosine deaminase activity in • Upper limb anomalies ~43% of cases
most patients (useful test to differentiate it –– Absent thumbs, triphalangeal thumbs
from transient erythroblastopenia of child- • Hypogonadal and genital changes (mostly
hood [TEC]) male) ~35% of cases
• Reticulocyte percentages are characteristi- –– Underdeveloped penis, undescended tes-
cally very low despite severe anemia tes, hypogonadism, malformation of
• Thrombocytosis or, rarely, thrombocytope- vagina, uterus
nia, and occasionally neutropenia, may also • Fanconi anemia “facies” ~23% of cases
be present –– Microcephaly, small eyes, epicanthal folds,
• Decreased RBC precursors in bone marrow abnormally shaped or absent ears
• Elevated serum iron • Renal malformations ~21%
• Normal bone marrow chromosomal studies –– Horseshoe kidney, absent or duplicate
• Negative parvovirus B19 titers kidney
• Cardiovascular, GI malformations ~11%
Treatment • Other skeletal findings like congenital hip
• Corticosteroids are the mainstay of therapy dysplasia
• Chronic transfusions initially for 1 year; • Intellectual disability (ID)
delaying steroids may also be considered to
prevent steroid side effects on growth and Laboratory
development in early infancy • Marrow failure usually starts in the first
• Iron-chelating agents (if transfusion-dependent) decade of life
• Stem cell transplantation for nonrespondents • Initial findings—macrocytosis and thrombo-
to corticosteroids, and after several years of cytopenia followed by granulocytopenia and
RBC transfusions then anemia
• Variable progression to full-blown pancyto- Laboratory/workup

penia due to aplasia • Neutropenia
• Diagnostic testing by diepoxybutane (DEB) • Abnormal pancreatic enzymes and
or mitomycin C assay to detect increased steatorrhea
chromosome fragility • Bone marrow showing myeloid hypoplasia
• Pancytopenia—60%
Complications • Abdominal imaging/GI consult for evalua-
• In addition to bone marrow failure and physi- tion of exocrine pancreatic insufficiency
cal anomalies, this is a cancer predisposition
syndrome Diagnosis
• Can lead to carcinoma of the head and neck, • SBDS mutation analysis is definitive in 90%
and upper esophagus, gynecological cancers
• Can also lead to advanced MDS and acute Complications—increase with age, usually after
leukemia 10 years of age
• Aplastic anemia
Treatment • MDS
• Supportive care and close observation if not • Acute myelogenous leukemia
transfusion-dependent
• Androgens may produce a response in 50% Treatment
of patients. Side effects—liver injury, peliosis • Androgen with low-dose prednisone
hepatis, liver tumors
• Hematopoietic stem cell transplantation
(HSCT) as a curative option NORMOCYTIC ANEMIA
• Approach to normocytic anemia (Fig. 10.6)
Shwachman–Diamond Syndrome
Genetics
Transient Erythroblastopenia
of Childhood
• Recurrent bacterial infections (secondary to • Most common acquired RBC aplasia in
neutropenia) childhood
• Exocrine pancreatic insufficiency → fat mal- • Temporary, self-limited in otherwise healthy
absorption (absence of steatorrhea does not child
exclude Shwachman–Diamond syndrome) →
failure to thrive Etiology
• Skeletal abnormalities: Short stature (metaph- • Suppression of RBC production
yseal chondrodysplasia); abnormal digits • May be seen after viral infection
(syndactyly, clinodactyly, or supernumerary
metatarsals) Clinical presentation (Table 10.2)
• Others: Abnormal facies (bifid uvula, cleft • Can occur from 1 month to 6 years (more
palate, dental dysplasia, hypertelorism, common at ages 1–4 years)
microcephaly), retinitis pigmentosa • Males more affected than females
Fig. 10.6 Approach to Normocytic Anemia

normocytic anemia. MCV MCV>70+Age and < 100
mean corpuscular
volume, G6PD glucose-
6-phosphate Decreased Production Increased Destruction Acute Blood Loss
dehydrogenase, DIC
disseminated
Intrinsic Extrinsic
intravascular coagulation
Hemoglobinopathy Immune
Sickle Cell Anemia Autoimmune Hemolytic anemia
SC Disease
Hb E Disease
Non-Immune
DIC
Enzyme Defect Hypersplenism
G6PD
Pyruvate Kinase Deficiency
Membrane Defect
Hereditary Spherocytosis
Hereditary Elliptocytosis
Laboratory Etiology
• Hgb usually 6–8 g/dL • Molecular defects in membrane proteins of
• Low reticulocyte count the RBC cytoskeleton, most commonly spec-
• MCV normal for age trin or ankyrin
• May have mild neutropenia • Reduction in surface-to-volume ratio causes
• Bone marrow biopsy rarely required spherocytes that are osmotically fragile and
• Normal adenosine deaminase (ADA) trapped by the spleen

• Reassurance • Neonatal period: Jaundice and hyperbilirubi-
• Complete recovery in 1–2 months nemia sufficient to require exchange
• Transfusion required only if symptomatic and transfusion
interfering with quality of life • Variably symptomatic based on severity
• Anemia
–– Pallor, fatigue, exercise intolerance
HEMOLYTIC ANEMIA • Splenomegaly
• Pigment gallstones at a young age
Hereditary Spherocytosis • Susceptible to aplastic crisis as a result of
parvovirus B19 infections
Background
–– Erythroid marrow failure may result rap-
• Most common erythrocyte membrane defect
idly in profound anemia, high cardiac out-
• Autosomal-dominant inheritance
put failure, hypoxia, cardiovascular
• Less frequently may be autosomal recessive
collapse; may have thrombocytopenia
• 30% have no family history and considered
sporadic
• Vaccination for encapsulated organism

Haemophilus influenzae, meningococcus,
pneumococcus should be given before sple-
nectomy, then prophylactic penicillin V
125 mg twice a day < 5 years and 250 twice a
day for > 5 years
Hereditary Elliptocytosis
• Also classified as a membrane defect of
Fig. 10.7 Red cells should be similar in size to 1/3 of cen-
tral pallor. In hereditary spherocytosis, the red cells lack cen- RBCs, but less common than hereditary
tral pallor and are hyperchromatic (40×). Red arrows point spherocytosis
out a few of the examples in this field • Autosomal dominant
• Clinical presentation similar as in hereditary
spherocytosis
Laboratory
• Normocytic anemia (Fig. 10.7) Laboratory
• Elevated mean corpuscular hemoglobin con- • Elongated, oval, or elliptically shaped RBCs
centration (MCHC) on peripheral smear
• Reticulocytosis –– May also see poikilocytes, spherocytes,
• Elevated LDH microcytosis, and fragmentation on smear
• Low haptoglobin
• Indirect hyperbilirubinemia Treatment
• Spherocytes on peripheral smear • No specific therapy if asymptomatic and min-
• Increased osmotic fragility imal hemolysis
–– Not reliable in neonatal period • Otherwise similar to hereditary
• Can also be diagnosed with flow cytometry spherocytosis
(eosin-5′-maleimide [EMA] binding test)
Treatment aroxysmal Nocturnal

P
• Folic acid supplementation to prevent Hemoglobinuria (PNH)
deficiency
• Indications for splenectomy Etiology
–– Severe disease • Originates from an acquired genetic mutation
–– Low Hgb with frequent need for in PIGA in hematopoietic cell membrane
transfusions –– PIGA involved in synthesis of a membrane
–– Aplastic crises anchor that links cell surface proteins to
–– Poor growth the plasma membrane on hematopoietic
–– End-organ damage—cardiomegaly cells
• Partial splenectomy can improve transfusion- • Lack of complement inhibitors CD55 and
dependent children with severe case, while CD59 on the RBC surface (no anchor)
theoretically preserving some splenic func- • Cells become destroyed by complement-
tion and protection against sepsis mediated lysis
• Severity of illness correlates with the size of S

ickle Cell Disease
the PNH clone
Background
Clinical presentation • Hemoglobin S is the result of a mutation in
• Aplastic anemia may precede the diagnosis the beta-globin chain, with a substitution of
of PNH valine for glutamic acid at the sixth position
• Nocturnal or morning hemoglobinuria (sign • Autosomal recessive
of intravascular hemolysis) • Complications arise from vascular–endothe-
• Hemolytic anemia lial dysfunction, nitric oxide deficiency,
–– Fatigue, jaundice inflammation, oxidative stress and reperfu-
• Thrombosis and thromboembolic phenomena sion injury, hypercoagulability, increased
may occur and can be severe—leading cause neutrophil adhesiveness, and platelet
of death activation
Laboratory Clinical presentation

• Anemia • Can be diagnosed on neonatal screen
• Reticulocytosis • Manifestations begin around 6 months of age,
• Negative DAT (Coombs test) when adult Hgb becomes dominant and Hgb
• Indirect hyperbilirubinemia F decreases
• Low LDH • Functional asplenia by around 5 years of age
• Decreased haptoglobin –– High susceptibility to infections
• Free serum hemoglobin –– Encapsulated organisms most common
• Flow cytometry for CD55 and CD59 • Large-vessel vasculopathy
–– Cerebrovascular disease
–– Pulmonary hypertension
Treatment
–– Priapism
• Acute
–– Retinopathy
–– RBC transfusions for severe anemia (Hgb
• Progressive ischemic organ damage
< 7 g/dL)
–– Hyposplenism
• Chronic
–– Renal failure
–– Eculizumab—anticomplement therapy
–– Bone disease
(binds to C5 and prevents its cleavage,
–– Liver damage
thereby inhibiting the formation of the
membrane attack complex [MAC], Laboratory
decreasing susceptibility to cell • Normocytic anemia
destruction) • Sickle cells on smear (Fig. 10.8)
◦◦ Reduces hemolysis, decreases need for • Hemoglobin electrophoresis shows Hgb S
transfusions, reduces risk of thrombosis, (SS, SC, S-beta-thalassemia)
and improves quality of life • May have elevated WBC count
–– Anticoagulation treatment for thrombosis
◦◦ No preventative anticoagulation indi- General considerations
cated unless high risk (hospitalized with • Hydroxyurea (HU) as preventative
illness, postsurgical) management
–– Allogeneic hematopoietic stem cell trans- –– Increases level of hemoglobin F and total
plant is the only curative treatment hemoglobin
• Osteomyelitis
–– Staph or salmonella
–– Treat with prolonged parenteral antibiotics
per infectious guidelines
Acute Chest Syndrome

• Occurs in as many as 50% of sickle cell dis-
ease (SCD) patients, major cause of hospital-
ization and mortality
Fig. 10.8 Peripheral smear (40 ×) from a patient with sickle Etiology
cell disease showing sickle cells (black arrows), target cells • Infection
(arrowhead), and a Howell–Jolly body (red arrow) –– Most commonly Streptococcus pneu-
moniae and Mycoplasma pneumoniae
–– Decreases the pain crises by 50%; prevents • Vaso-occlusion
splenic dysfunction, cerebral artery dam- • Hypoventilation secondary to pain (pain cri-
age, and stroke sis commonly precedes development of ACS)
–– If begun in infancy, may preserve the • Atelectasis
splenic function and decrease acute chest • Thromboembolism
syndrome (ACS)
–– Initial dose is 20 mg/kg, increase gradually Clinical presentation
by 2.5–5 mg/kg up to a max of 35 mg/kg/day • Fever
–– Monitor for toxicity—mainly myelosup- • Chest pain
pression • Hypoxemia
–– Glutamine (Endari) can be given with HU • Respiratory distress
for prevention of morbidities • New infiltrate on chest radiograph
• Fever
–– Medical emergency—increased risk of Treatment
bacteremia, sepsis, meningitis, pneumonia/ • Antibiotic coverage
ACS –– Macrolide
–– Draw blood culture and perform chest –– Third generation cephalosporin
radiograph • Pain management
–– Initiate parenteral third-generation cepha- • Simple RBC transfusion for hypoxemia
losporin (i.e., ceftriaxone) × 2 doses and • Exchange transfusion indications
treat other causes if identified –– Continued hypoxemia and worsening respi-
ratory distress in the setting of Hgb > 10 g/dL
Infection • Can lead to risk of pulmonary hypertension—
• Due to functional hyposplenism leading cause of mortality in adults with EPO
• Infectious prophylaxis
–– Penicillin V potassium (VK) Vaso-occlusive Crisis
◦◦ Orally from birth until 5 years of age • Disruption of blood flow in microvasculature
◦◦ 125 mg orally twice a day 0–3 years by sickle cells, which have reduction in
◦◦ 250 mg orally twice a day 3–5 years deformability and increased adhesion to endo-
–– Continue prophylaxis for life if there is a thelial cells
history of severe infection with encapsu- • Risk factors include increased activity, expo-
lated organisms, splenectomy sure to cold, infection, hypoxia, and acidosis
• Presents as pain most often in the chest, back, Clinical presentation

abdomen, and extremities • Rapidly enlarging spleen
• Acute drop in hemoglobin (at least 2 g/dL
Treatment from baseline) with reticulocytosis
• IV hydration • Can lead to hypovolemic shock and death
• Anti-inflammatory medications—NSAIDs,
acetaminophen Treatment
• Often requires opioids and hospitalization for • IV hydration for hemodynamic stability
severe pain crises • RBC transfusion
Prognosis
Prevention
• Parents should be taught to palpate spleen
• Hematologists offer HU to all patients over
• Repeat episodes are common
the age of 9 months with SS or Sβ 0 thalas-
• Mortality rate is as high as 10–15%
semia, and Endari (glutamine) to all children
with SCD over the age of 5 years
Aplastic Crisis
Dactylitis Etiology
• Pain and swelling of the hands and feet • Arrest of erythropoiesis, leading to profound
• Often the first presentation of pain in toddlers and acute drop in hemoglobin
with SCD • Occurs most commonly secondary to infection
• Occurs in 50% of children by 2 years of age –– Parvovirus B19
• Differential diagnosis may include osteomy- –– May also be caused by bacterial and other
elitis if unilateral viral infections
• Treatment with anti-inflammatory pain medi-
cations, including acetaminophen and Clinical presentation
NSAIDs • Pallor
• Fatigue
Priapism • Decreased activity
• Prolonged penile erection in the absence of • Poor feeding
stimulation • Altered mentation
• May lead to irreversible changes—tissue
necrosis, fibrosis, erectile dysfunction Laboratory
• If < 2–4 h, treatment with hydration, oral pain • Severe anemia
management • Reticulocytopenia
• If > 4 h, medical emergency • May have thrombocytopenia
–– IV hydration
–– IV analgesics Treatment
–– Aspiration of blood from the corpus caver- • Transient with recovery of reticulocytes
nosum followed by injection of an alpha- within 2–14 days
adrenergic agonist • RBC transfusion support until reticulocyte
recovery
Splenic Sequestration
• Caused by vaso-occlusion in the spleen— Neurologic Complications
pooling of RBCs • Up to 11% of patients with SCD will have
• May occur in up to 30% of children with SCD clinically apparent stroke by the age of 20 years
• Ischemic stroke more common in children Renal Disease

• Can also have silent infarctions and transient • Renal infarction and papillary necrosis
ischemic attacks (TIAs), which cause neuro- • Proteinuria
cognitive and behavioral defects • Hematuria
–– Poor learning in school, academic failure • Diminished concentrating ability
(hyposthenuria)
Clinical presentation • Renal tubular acidosis
• Headache • Urinary tract infections, pyelonephritis
• Focal weakness • Hypertension
• Altered mental status • Treatment
• Seizures –– IV hydration with gross hematuria
• Posterior reversible encephalopathy syn- –– ACE inhibitors in chronic kidney disease
drome (PRES) and hypertension
• Cerebral venous sinus thrombosis ◦◦ Lower protein excretion by > 50%
Imaging
Other Complications
• Overt stroke means presence of focal neuro-
• Delayed puberty
logical deficit > 24 h and or cerebral infarct
• Impaired growth
by T2-weighted MRI
• Avascular necrosis
• Silent stroke means absence of focal neuro-
–– Most often femoral and humeral heads
logical lesions > 24 h with cerebral infarct on
–– Progressive joint destruction seen on MRI
T2-weighted MRI
–– Treatment with pain management, surgical
Treatment core decompression, may progress to
• Immediate (STAT) computed tomography require hip replacements in adult life
(CT)/MRI • Retinopathy
• Initially simple RBC transfusion to raise Hgb –– Due to retinal artery occlusion and ischemia
to 10 g/dL –– Can progress to retinal detachment
• Exchange transfusion –– Annual ophthalmologic examination for
–– Goal is to decrease HbS to < 30% early detection
–– Requires placement of apheresis catheter
Primary prevention of stroke yruvate Kinase Deficiency

P
• Transcranial Doppler (TCD) to measure
blood velocity Introduction
–– If > 200 cm/s, prophylactic transfusion • PK deficiency is an inherited autosomal-
indicated to decrease Hgb S to < 30% recessive RBC enzyme disorder that causes
chronic hemolysis
Secondary prevention of stroke • PK is an active enzyme in Embden–
• Initiation of RBC transfusion therapy after Meyerhof–Parnas pathway (glycolytic
first stroke to prevent recurrent episodes to pathway)
keep Hgb S < 30% • Deficiency leads to defective RBC glycolysis
• Cessation of transfusion associated with and decreased adenosine triphosphate (ATP)
recurrence production, leading to rigid and deformed
• Risk of iron overload RBCs with decreased RBC survival
–– Treat with iron-chelating agents • Unlike G6PD deficiency, the hemolysis is
–– Deferoxamine (IV), deferasirox (orally), present at all times and is not precipitated by
deferiprone (orally) exposure to drugs
Clinical presentation Pathophysiology

• Clinical course can vary. Can cause severe • G6PD catalyzes conversion of glucose
neonatal hemolytic anemia leading to jaun- 6-phosphate to 6-phosphogluconic acid,
dice and kernicterus or can be mild like well- which produces NADPH, which keeps gluta-
compensated hemolysis first noted in thione (GSH) in the reduced functional state
adulthood • Reduced GSH is necessary for protection
• Signs and symptoms of hemolytic anemia against oxidant threats from certain drugs and
may be present: Pallor, icterus, splenomegaly, infections
gallstones, leg ulcers, etc. • G6PD activity falls rapidly as RBC ages,
which leads to decreased glucose metabo-
Laboratory lism and impaired elimination of oxidants
• Significant reticulocytosis; becomes more and subsequent loss of RBC membrane
pronounced after splenectomy integrity
• Smear shows polychromasia and mild macro- • Severity of hemolysis depends on the quan-
cytosis to reflect the elevated reticulocyte tity and type of G6PD deficiency and nature
count of hemolytic agent (usually an oxidation
• Pyknocytes may be seen mediator)
Treatment Genetics
• Phototherapy and exchange transfusions for • X-linked recessive
hyperbilirubinemia in newborns • Variable intermediate expression shown by
• RBC transfusion for severe anemia as heterozygous females due to variable
necessary X-inactivation (lyonization)
• Splenectomy should be performed after the • More common in African American,
child is 5–6 years of age, if requiring frequent Mediterranean, Middle Eastern, and Asian
transfusions ethnic groups
• Folate supplementation
• Most individuals are asymptomatic, unless
Glucose-6-Phosphate hemolysis triggered
Dehydrogenase Deficiency • Episodes of hemolysis are produced by infec-
tion, drugs, and ingestion of fava beans
Introduction • Hemolysis ensues usually about 24–48 h after
• G6PD is an enzyme involved in the hexose exposure
monophosphate pathway, essential for glu- • Drugs causing hemolysis include antioxidant
cose metabolism in RBCs, with a vital role in drugs like aspirin, sulfonamides, antimalari-
prevention of cellular damage from reactive als, and rasburicase
oxygen species (ROS) • Ingestion of fava beans can cause acute life-
• G6PD deficiency affects more than 400 mil- threatening hemolytic syndrome
lion people worldwide, overall 4.9% global • G6PD deficiency can also cause severe neo-
prevalence natal jaundice, even leading to kernicterus in
• Global distribution parallels that of malaria some types
• Clinically presents with two clinical • In patients with chronic nonspherocytic
syndromes: hemolytic anemia, patients can have chronic
–– Episodic hemolytic anemia (more common) hemolysis and splenomegaly and may require
–– Chronic nonspherocytic hemolytic anemia frequent blood transfusions
Laboratory Clinical presentation

• Normocytic anemia • Manifestations of hemolysis or, if the enzy-
• Reticulocytosis with polychromasia may be mopathy is present in other tissues, may
seen involve other organ systems
• Low haptoglobin, hemoglobinuria in severe
episodes Enzyme deficiencies
• RBCs with Heinz bodies due to hemoglobin • Hexokinase deficiency
precipitation (need supravital stain), bite cells • Glucose phosphate isomerase deficiency
may be seen • Aldolase deficiency
• Diagnosis demonstrated by reduced G6PD • Diphosphoglycerate deficiency
activity in RBCs • Enolase deficiency
• Immediately after a hemolytic episode, retic- • Phosphofructokinase deficiency
ulocytes and young RBCs predominate. –– Myopathy
These young cells have significantly higher –– Associated with type VII glycogen storage
enzyme activity than do older cells, so G6PD disease
testing may be falsely negative for G6PD –– Common in Ashkenazi Jews
deficiency. Test should be repeated a few • Triose phosphate isomerase deficiency
weeks after the hemolytic episode –– Cardiac anomalies
–– Recurrent infections
Treatment –– Progressive neuromuscular disease with
• Prevention of hemolysis generalized spasticity
• Special consideration given while prescribing • Phosphoglycerate kinase deficiency
the known oxidant drugs in patients (espe- –– First ATP-generating enzyme
cially males belonging to ethnic groups with –– Sex-linked recessive
high incidence of G6PD deficiency) –– ID
• If hemolysis has occurred, discontinue the –– Seizures
oxidant agent –– Behavioral disorders
• Blood transfusion as needed for severe
hemolysis
Autoimmune Hemolytic Anemia
Other Enzyme Deficiencies Introduction

• Antibodies are formed against antigens on
Background RBC surface, which destroys the RBC, lead-
• Sole energy source of erythrocytes is the gly- ing to hemolysis
colytic production of ATP. Thus, any defect in • Hallmark is positive DAT (Coombs test),
the various enzymes in the glycolytic path- which detects a coating of immunoglobulin/
way can lead to hemolytic anemia complement on the RBC surface
• Mostly transmitted as autosomal recessive,
except: Etiology
–– Phosphoglycerate kinase (PGK) • Antibodies may be produced as an inappro-
deficiency-X-linked abnormality priate immune response to an RBC antigen
–– Adenosine deaminase (ADA) overproduc- (Ag) or to another epitope similar to an RBC
tion is an autosomal dominant disorder Ag (molecular mimicry)
• An infectious agent may alter the RBC mem- purpura sometimes occurs—Evans
brane so that it become antigenic syndrome)
• Drugs ~20% of cases, e.g., penicillin and –– The direct antiglobulin test is strongly
cephalosporins, etc. positive
• IgM cold antibodies usually associated with • Treatment
infections, e.g., mycoplasma and Epstein– –– Supportive treatment for mild cases
Barr virus (EBV) –– Corticosteroids for IgG-mediated disease
–– Blood transfusion (blood unit with the
Two types of autoimmune hemolytic anemia least reaction by the Coombs tech-
(AIHA) nique)—transient benefit, lifesaving in
1. Warm AIHA severe anemia
• Antibodies are active at 35–40 °C (“warm” –– IVIG
antibodies) –– Splenectomy in persistent cases
• Most often belong to the IgG class. They
do not require complement for activity 2. Cold Agglutinin Disease
2. Cold AIHA (cold agglutinin disease) • Cold antibodies usually have specificity
• Cold antibodies agglutinate RBCs at tem- for the oligosaccharide antigens of the I/i
peratures < 37 °C (98.6 °F) blood group system
• They are primarily of the IgM class and • They may occur in primary or idiopathic
require complement for hemolytic activity cold agglutinin disease, secondary to infec-
tions such as those from Mycoplasma
1. Warm AIHA pneumoniae and EBV or secondary to
• Clinical presentation lymphoproliferative disorders
–– Can be acute or chronic • Cold agglutinin disease is less common in
–– Acute transient type lasting 3–6 months, children than in adults
mainly in children 2–12 years—70–80% • More frequently results in an acute, self-
of patients. Frequently preceded by an limited episode of hemolysis
infection • Glucocorticoids not effective
–– Spleen is usually enlarged and is the pri- • Patients should avoid exposure to cold and
mary site of destruction of antibody- should be treated for underlying disease
coated RBCs • If severe, treatment includes immunosup-
–– This form characterized by a consistent pression and plasmapheresis
response to steroids, a low mortality • Splenectomy is not useful in cold aggluti-
rate, and full recovery nin disease
–– Other clinical patterns have a prolonged
and chronic course, more frequent in
infants and in children > 12 years. P aroxysmal Cold Hemoglobinuria
Hemolysis may continue for many
months or years • Mediated by the Donath–Landsteiner (D-L)
• Laboratory antibody
–– Profound anemia • An IgG cold-reactive autoantibody with anti-
–– Considerable reticulocytosis, spherocy- P specificity
tosis, and polychromasia. (in some • In vitro, the D-L antibody binds to RBCs in
cases, a low reticulocyte count may be the cold, and the RBCs are lysed by comple-
seen, particularly early in the episode) ment as the temperature is increased to 37 °C
–– Leukocytosis • Most reported cases are self-limited
–– Platelet count is usually normal, but • Most cases are associated with nonspecific
concomitant immune thrombocytopenic viral infections
• Previously congenital or acquired syphilis Laboratory

used to be the most common underlying cause • Counts 2–3/week for 6 weeks, genetic
of paroxysmal cold hemoglobinuria testing
• Accounts for 30% of immune hemolytic epi-
sodes among children Treatment
• Treatment includes transfusion for severe • Prophylactic G-CSF during nadir in some
anemia and avoidance of cold ambient cases
temperatures • Immediate attention to fevers
HITE BLOOD CELL

W Chronic Benign Neutropenia
DISORDERS • No specific underlying etiology found
• No serious infections
Neutropenia
Acute thnic Neutropenia/Benign Familial

E
Neutropenia
• Viral infection: EBV, respiratory syncytial
virus, influenza A and B, parvovirus, hepati- • Seen in patients of African American,
tis, human herpesvirus 6 (HHV6) infections, Mexican, and Mediterranean descent: No
measles, rubella treatment
• Bacterial infection
• Hypersplenism
• Drug-induced—recovery after medication Congenital Neutropenia
cessation
–– Antimicrobials: Sulfonamides, penicillin Kostmann Syndrome (Severe
–– Antirheumatics: Gold, phenylbutazone, Congenital Neutropenia)
penicillamine
–– Anticonvulsants: Phenothiazine • Autosomal recessive
–– Analgesic and anti-inflammatory: Ibuprofen
• Skin infections and abscesses—most
Chronic common
• Pneumonia and deep tissue abscesses—often
Cyclic Neutropenia life-threatening
• Mouth ulcers, gingivitis
Clinical presentation • Otitis media
• Approximately 2-day cycles with changing • Mild hepatosplenomegaly (HSM)
neutrophil counts with neutropenia spanning • Bone marrow arrest
3–6 days • Progress to MDS/AML
• Nadir may be in severe range
• During nadir, the following can develop: Treatment
Fever, oral ulceration, gingivitis, pharyngitis, • G-CSF
skin infections, and occasionally serious • Stem cell transplant for MDS/AML
infections (pneumonia, necrotizing enteroco-
litis with peritonitis, and Escherichia coli (E.
coli) or Clostridium sepsis)
Fanconi Anemia Bone Marrow Infiltration

Cartilage Hair Hypoplasia Malignancy
• MDS
Chediak–Higashi Syndrome • Lymphoproliferative disorders
Immune Pancytopenia
• Autoimmune neutropenia • Reduction in the number of RBCs, WBCs,
• Neonatal alloimmune neutropenia and platelets below age-adjusted lower limit
• Dysgammaglobulinemia of normal
• Hyper IgM syndrome –– Anemia, leukopenia, thrombocytopenia
• HIV
• PNH Results from: (Table 10.3)
• Decreased production of blood cells or bone
marrow failure
Nutritional • Immune-mediated destruction
• B12 and folic acid deficiency—Ineffective • Non-immune-mediated sequestration in
erythropoiesis with possible associated periphery
neutropenia
Table 10.3 Differential diagnosis of pancytopenia

Congenital/inherited Acquired
Mechanism Decreased bone marrow Decreased bone marrow production Increased destruction/sequestration
production
Common Fanconi anemia Chemotherapy Liver disease
causes Gaucher disease Radiation therapy Portal hypertension
Megaloblastic anemia
Bone marrow infiltration
Myelodysplasia
Myelofibrosis
Aplastic anemia
Connective tissue disorders
(Rheumatoid arthritis, SLE)
Acute viral infections (CMV, EBV)
HIV
Mycobacterial infection
Uncommon Bone marrow failure Paroxysmal nocturnal hemoglobinuria Hypersplenism secondary to
causes syndromes myelo- and lymphoproliferative
disorders
Dyskeratosis congenita Anorexia nervosa Hemophagocytic syndromes
Congenital GVHD Drug-induced immune pancytopenia
amegakaryocytic
thrombocytopenia
Shwachman syndrome Heavy-metal poisoning Evans syndrome with tricytopenia
Infection (parvovirus, HHV6, or CMV Infection (brucellosis, visceral
in transplant recipients, legionnaires’ leishmaniasis)
disease)
SLE systemic lupus erythematosus, CMV cytomegalovirus, EBV Epstein–Barr virus, GVHD graft-versus-host disease, HHV6
human herpesvirus 6
Signs and symptoms Table 10.4 Causes of aplastic anemia

• Weakness Acquired Inherited
• Fatigue Secondary Fanconi anemia
• Easy bruising and bleeding Radiation Dyskeratosis congenita
Drugs Shwachman–Diamond
• Pallor syndrome
• Tachycardia Chemotherapy Amegakaryocytic
• Shortness of breath thrombocytopenia
• Infections Antiepileptics Diamond–Blackfan
anemia
Management and treatment Anti-inflammatory Familial aplastic
Antithyroid anemias
• Depends on etiology Toxic chemicals
• Treat underlying cause Benzene
• Immunosuppression Solvents
• Drugs to stimulate bone marrow Viruses
EBV
• Bone marrow transplant
Hepatitis (non-A, B, C, E,
• Supportive care or G)
–– Blood transfusions HIV
Immune diseases
Eosinophilic fasciitis
Aplastic Anemia SLE (uncommon)
GVHD
Paroxysmal nocturnal
• Decreased production of mature blood hemoglobinuria
cells Pregnancy
–– Due to reduction in the number or function Myelodysplasia
of progenitor cells Idiopathic
• Characterized by pancytopenia and hypocel- EBV Epstein–Barr virus, SLE systemic lupus erythematosus,
lular bone marrow GVHD graft-versus-host disease
• Injury or loss of pluripotent hematopoietic
cells in the absence of infiltrative disease of
the bone marrow
• Acquired and inherited causes (Table 10.4)
• Most cases are idiopathic with no identifiable
underlying cause
• Vital to distinguish inherited vs. acquired in
order to guide management and treatment
• Diagnosis made by bone marrow aspiration
and biopsy (aplastic anemia Fig. 10.9) [3]
(normal bone marrow Fig. 10.10) [4]
–– Profoundly hypocellular bone marrow with
decrease in all elements
–– Marrow space composed of fat cells and
Fig. 10.9 Aplastic anemia: Bone marrow biopsy of a teen-
marrow stroma age girl with aplastic anemia whose marrow is strikingly
–– Residual hematopoietic cells are normal hypocellular for age. (From Rogers [3], with permission)
PLATELET DISORDERS
• Approach to platelet disorders (Fig. 10.11)
Thrombocytopenia
Diagnosis
• Normal platelet count 150,000–450,000
• Low platelet count may be due to clump-
ing in the tube and can be ruled out on
blood smear or pseudothrombocytopenia
screen
Fig. 10.10 Normal bone marrow biopsy of a 4-year-old boy.
Marrow cellularity is estimated by the percentage of hemato- • Differential guided by platelet count, platelet
poietic cells in the total volume of marrow space. Marrow size, the presence of other cytopenias, and
cellularity declines with age, with the highest cellularity in cause from low production or excessive
infants and young children and the lowest cellularity in the consumption
elderly (estimated cellularity = 100 minus age). The current
biopsy has approximately 90–96% cellularity (100–4 = 96).
(From Schafernak and Calvo [4], with permission)
Increased Consumption
Kasabach–Merritt Syndrome
• Platelet destruction due to high-velocity
turbulent blood flow through venous

malformation
• May also be associated with abnormal coagu-
lation profile
• Urgent venous malformation treatment and
supportive care required
Fig. 10.11 Approach to

Platelet Number/Function
platelet disorders. ITP
immune
thrombocytopenic
Number Abnormal function
purpura, TTP thrombotic
thrombocytopenic
purpura, HUS hemolytic Production Destruction Sequestration Congenital
uremic syndrome, DIC “Hypersplenism” Glanzmann
disseminated thrombasthenia
intravascular coagulation Bernard-Soulier
Immune
Decreased Syndrome
Megakaryopoiesis ITP
Aplastic Anemia Drugs
Marrow infiltration
Chemotherapy Acquired
Non-Immune
Uremia
TTP
Drugs
Ineffective HUS
Megakaryopoiesis DIC
B12/Folate deficiency
Methotrexate
Immune Thrombocytopenic Purpura (ITP) • High LDH, high indirect bilirubin, anemia,
• Autoimmune destruction of platelets thrombocytopenia, elevated creatinine, posi-
• Large platelet size indicates rapid production tive Shiga toxin
and release of new platelets from the marrow • Typically associated with hemorrhagic diar-
• Often associated with a preceding viral rhea due to Shiga toxin produced by E. coli
illness O157
• Typically self-limited, resolving within sev- • Aggressive supportive care needed for kidney
eral weeks failure, and anemia
• Chronic ITP if lasting > 6 months, and more
likely to be associated with a rheumatologic Thrombotic Thrombocytopenic Purpura
condition • Dysfunction of ADAMTS13 due to acquired
• Intracranial or mucosal bleeding are the most autoantibody/inhibitor or congenital
severe complications mutation
• Observation is typically sufficient. Treatment • Lack of ADAMTS13 function leads to failure
with IVIG or steroids is indicated with sig- to cleave large von Willebrand multimers
nificant bleeding • Intravascular shearing on large vWF multim-
ers; causes hemolytic anemia and thrombocy-
Hemolytic Uremic Syndrome topenia, kidney failure, encephalopathy, and
• Thrombocytopenia associated with microan- multisystem organ dysfunction
giopathic hemolytic anemia and kidney
failure
• Clinical symptoms include bloody diarrhea, Decreased Production
fever, vomiting, and decreased urine output
• Renal failure, thrombocytopenia, and hemo- Marrow Suppression
lytic anemia usually present 5–10 days after • Medication effect
initial symptoms and diarrhea has already • Marrow suppression due to infection, typi-
resolved cally viral
• Blood smear demonstrates schistocytes, indi-
Neonatal Thrombocytopenia
cating intravascular destruction of RBCs
• Severe thrombocytopenia in the neonatal
(Fig. 10.12)
period can be dangerous due to the risk of
intracranial hemorrhage
• Neonatal alloimmune thrombocytopenia
(NAIT): Profound thrombocytopenia due to
maternal antibodies against infant’s platelets
• Family history of other siblings with neonatal
thrombocytopenia should raise concern for
an inherited disorder of platelet production
Amegakaryocytic Thrombocytopenia
• Autosomal recessive disorder of failure of
bone marrow to make megakaryocytes, and
in turn, platelets
Fig. 10.12 Peripheral smear (40 ×) from a patient with
hemolytic anemia showing a schistocyte (black arrow) as • Associated with other congenital malforma-
well as fragmented cells (arrowheads). Note the presence of tions including cardiac, kidney, and
nucleated red cells (red arrows) musculoskeletal
Thrombocytopenia Absent Radii Syndrome A cquired Bleeding Disorders

(TAR)
• Thrombocytopenia and lack of development Vitamin K Deficiency
of radii
• Associated with congenital heart disease • Vitamin K-dependent factors: II, VII, IX, X,
• May require platelet transfusion support C, S
• Platelet count typically improves over time • Vitamin K deficiency can occur due to pro-
longed antimicrobial use or liver failure
• PT will be prolonged before change is seen in
Abnormal Function PTT, as factor VII has the shortest half-life
• Replace with vitamin K if mild, or FFP to
Glanzmann Thrombasthenia replace clotting factors if severe bleeding
• Severe platelet dysfunction due to genetic
mutation affecting glycoprotein IIb/IIIa Hemorrhagic Disease of the Newborn
• Normal platelet count, but excessive bleeding
due to lack of function • Newborns are vitamin K-deficient at birth
• Diagnosed via platelet aggregation studies due to lack of placental transfer of vitamin K
and lack of mature gut flora at birth.
Wiskott–Aldrich Syndrome Prophylactic intramuscular vitamin K given
• Thrombocytopenia at birth
• Small platelet size • If vitamin K is not given, newborn will not
• Eczema have adequate clotting factors and is at risk
• Recurrent or severe infections due to for hemorrhage
immunodeficiency • Classical form of hemorrhagic disease of the
• X-linked mutation in WAS gene newborn includes mucosal or subcutaneous
bleeding, bleeding at venipuncture or proce-
Bernard–Soulier Syndrome dure sites within the first week of life
• Severe platelet dysfunction due to autosomal- • Delayed form includes breastfed infants
recessive mutation affecting glycoprotein Ib, within the first 4 weeks of life and can include
making platelets unable to bind von intracranial hemorrhage
Willebrand factor
• Large platelets; may be normal in number Disseminated Intravascular
Coagulopathy
COAGULATION DISORDERS • Severe systemic process of coagulation factor
and platelet consumption, with diffuse clot-
Bleeding Disorders ting and bleeding. High mortality rate
• Detected by thrombocytopenia, elevated PT/
1. Suspect bleeding disorder if recurrent or severe
PTT, and decreased fibrinogen
bleeding or bruising, frequent/prolonged epi-
• Caused by severe sepsis, malignancy, trauma,
staxis, severe bleeding with procedures or den-
tal extractions, or a family history burns, or severe multisystem illness
2. Workup includes PT/INR, PTT, platelet count,
fibrinogen, von Willebrand panel, and poten- I nherited Bleeding Disorders
tially specific factor levels
3. Petechiae indicate thrombocytopenia. Purpura Hemophilia A and B
typically indicates a more profound diffuse sys-
temic illness, including disseminated intravas- • Suspect if prolonged bleeding with circumci-
cular coagulation (DIC), sepsis, or vasculitis sion, joint bleed, or muscle bleed
• May be detected with prolonged PTT and ERYTHROCYTOSIS

confirmed with factor VIII or factor IX level.
Platelet count and PT are normal Definition
• Hemophilia A = congenital deficiency of fac- • Increase in erythrocyte count, hemoglobin,
tor VIII, about 85% of patients and hematocrit above the age, sex, race, and
• Hemophilia B = congenital deficiency of fac- altitude-adjusted reference range
tor IX, about 15% of patients • Absolute erythrocytosis: Increase in total red
• Both forms are X-linked cell mass
• Severity depends on the level of deficient fac- • Relative erythrocytosis: Secondary to severe
tor: Severe (< 1%), moderate (1–5%), or mild plasma volume reduction
(> 5%)
• With suspicion for intracranial hemorrhage Clinical presentation
such as vomiting, altered mental status, • Hypertension, headache, shortness of breath,
headache, or history of head trauma, treat neurologic symptoms; thrombocytosis may
immediately with factor and then obtain cause hemorrhage and thrombosis
imaging
• With suspicion for joint bleed or deep muscle
bleeding, treat with factor VIII (FVIII) immedi- Primary
ately. Repeated joint bleeds lead to destruction
• Low EPO concentration
of the joint capsule and progressive arthritis
• Acquired
Von Willebrand Disease

Polycythemia Vera
• Suspect if prolonged mucosal bleeding,
• Major criteria
including epistaxis or menorrhagia
–– Hgb > 16.5 g/dL (men) and > 16.0 g/dL
• Most common inherited bleeding disorder
(women) or
• Normal coagulation profile. Detected via von
–– VHct > 49% (men) and > 48% (women) or
Willebrand panel assessing antigen level and
–– RBC mass > 25% above mean
activity level of von Willebrand proteins
–– Bone marrow biopsy showing hypercellu-
• Multiple types of von Willebrand disease:
larity and trilineage growth with mature
–– Type 1—Quantitative defect and most
megakaryocytes
common
–– Presence of JAK2 mutation
–– Type 2 A—Defective von Willebrand fac-
tors cannot coalesce and form large vWF
multimers Secondary
–– Type 2B—Overbinding of glycoprotein I b
on platelets to von Willebrand proteins • High EPO concentration
causes rapid clearance of platelets and
large multimers Clinical presentation
–– Type 2M and 2N—Qualitative defects with • Hyperviscosity, hypertension, headache
all sizes of von Willebrand proteins –– Congenital
• Treatment for bleeding in von Willebrand dis- ◦◦ Hgb variants with high oxygen affinity/
ease is patient- and type-dependent but may hemoglobinopathy
include desmopressin or factor VIII/vWF ◦◦ 2,3-biphosphoglycerate deficiency
concentrate (Humate-P, CSL Behring) ◦◦ Familial erythrocytosis types 2–4
–– Acquired • Ecchymoses, petechiae

◦◦ Hypoxia • Bone and joint pain, particularly in lower
◦◦ Altitude extremities
◦◦ Cardiac disease –– Patients may present with refusal to bear
◦◦ Lung disease weight
◦◦ Central hypoventilation • Fatigue
• Anorexia
Other • Extramedullary spread
• Endocrine tumor (e.g., pheochromocytoma) –– Lymphadenopathy
• Tumor/cysts (e.g., nephroblastoma, renal cell –– Hepatosplenomegaly
carcinoma) –– Headache
• Renal artery stenosis ◦◦ Chills/fever: Central nervous system
• Neonatal (trisomies, infant of a diabetic (CNS) disease
mother, congenital adrenal hyperplasia) ◦◦ Rarely: Patient with cranial nerve palsies
–– Testicular enlargement
Treatment –– Orthopnea, cough
• Periodic phlebotomy ◦◦ Mediastinal mass
• Goal: To reduce risk of thrombosis without –– Skin lesions
increasing bleeding tendency –– Gingival hypertrophy
Peripheral blood abnormalities

NEOPLASTIC DISORDERS • Anemia
• Thrombocytopenia
Acute Leukemia • WBC abnormalities
–– Neutropenia
Epidemiology –– Elevated WBC
• Most common malignancy in children (30% ◦◦ 20% with WBC > 50,000 on presentation
of pediatric malignancy) – – Lymphoblasts on peripheral smear—
• Five times more common than acute myeloid peripheral blood usually shows leukocyto-
leukemia (AML) sis with a population of large mononuclear
cells (Fig. 10.13)
• Flow cytometry diagnosis
Acute Lymphoblastic Leukemia (ALL) • Evaluate for tumor lysis
Epidemiology Diagnostic evaluation

• 3.4 cases per 100,000 per year in the United • Flow cytometry
States –– 70 to 80% pre-B ALL
• Incidence higher in Whites and Hispanics –– 15 to 17% T-cell ALL
than in African Americans • Bone marrow aspirate and biopsy (Fig. 10.14)
• Peak incidence: 2–5 years of age [5]
• More common in boys • Lumbar puncture to evaluate for CNS disease
Clinical presentation Treatment

• Fever • Per local or national chemotherapy protocols
• Pallor
Associated Syndromes/Risk Factors
Trisomy 21
• Predisposed to developing acute leukemia
–– 10 to 20% higher risk of developing leuke-
mia than general population
• Worse outcome compared to non-trisomy 21
patients
–– Higher treatment-related mortality
–– Higher relapse rate
• Leukemia in trisomy 21 differs in clinical
features, timing of occurrence, and response
Fig. 10.13 Peripheral blood showing leukocytosis with a to therapy
population of large mononuclear cells with high nuclear- • AML occurs earlier compared to general
cytoplasmic ratio, scant blue cytoplasm, and fine chromatin population (1.8 vs 7.5 years); ALL has simi-
with occasional nucleoli. These are features of lymphoblasts. lar age distribution
Note scattered smudge cells, another feature often seen in
• Ratio of AML to ALL is roughly equal in
peripheral smears with leukemia
children with trisomy 21 vs 1:4 in children
without trisomy 21
–– Ratio approaches general population above
age 5 years
• 10 to 30% of infants with trisomy 21 develop
a transient myeloproliferative disorder or
transient leukemia
–– Detected on routine screening
–– Most patients are asymptomatic
–– Spontaneous resolution by 2–3 months of
age
–– 20% of patients later develop AML
Bloom syndrome
• Autosomal-recessive disorder; genomic
instability with DNA repair defects
• Growth retardation, inflammatory skin
changes due to hypersensitivity to UV light,
telangiectatic skin
• Predisposition to malignancy, especially leu-
kemia, lymphoma, and GI tract tumors
Fig. 10.14 Bone marrow biopsy of B-cell acute lympho-
blastic leukemia demonstrating replacement of normal
hematopoietic cells with lymphoblasts with round or slightly
Ataxia telangiectasia
irregular nuclei with condensed chromatic, without nucleoli. • Increased risk of developing malignancy, par-
(From Penchansky [5], with permission) ticularly leukemia (ALL) and lymphoma
Fanconi anemia • Evaluate for tumor lysis

• Inherited bone marrow failure syndrome • May have DIC
• Chromosome fragility/breakage
• Pancytopenia, radial bone abnormalities, kid- Diagnostic evaluation
ney, skin, or GI abnormalities • Flow cytometry
• Increased risk of leukemia • Bone marrow aspirate and biopsy
–– Morphologic and immunophenotypic
assessment
Acute Myeloid Leukemia (AML) • Lumbar puncture to evaluate CNS for
disease
Epidemiology Treatment
• 15% of childhood leukemia; less common • Per local or national protocols
than ALL • Two courses of intensive induction chemo-
• Overall survival 65–70%; remains lower than therapy followed by either cytarabine-based
children with ALL consolidation or hematopoietic cell
transplantation
• Similar to ALL: Fever, malaise, musculoskel-
etal pains, lymphadenopathy, hepatospleno- Associated Syndromes/Risk Factors
megaly, bleeding
• Ionizing radiation
• Reflective of leukemic burden
• Organic solvents
Peripheral blood abnormalities • Paroxysmal nocturnal hemoglobinuria
• Anemia • Trisomy 21
• Thrombocytopenia • Bloom syndrome
• WBC • Fanconi anemia
–– Decreased, normal, or increased • Kostmann syndrome
–– Leukemic myeloblasts noted on peripheral –– Severe congenital neutropenia
smear (Fig. 10.15) –– Risk of progression to AML
• Flow cytometry diagnosis –– Significantly improved survival with
G-CSF
• Shwachman–Diamond syndrome
–– Bone marrow dysfunction, most com-
monly neutropenia
–– Metaphyseal chondrodysplasia
–– Exocrine pancreatic deficiency
• Diamond–Blackfan syndrome
–– Congenital pure red aplasia with resultant
anemia
◦◦ Other cell lines often normal
–– Short stature
–– Thumb malformations
–– Other congenital anomalies
Fig. 10.15 Peripheral blood showing two myeloblasts with • Neurofibromatosis type 1
a high ratio of nucleus to cytoplasm, finely dispersed chro- –– Bone marrow failure
matin and one or more large nucleoli (arrows). Acute –– Predisposition to cancers, especially AML
myeloid leukemia represents only 20% of childhood and neuroblastoma
leukemia
hronic Myelogenous Leukemia

C –– Lymphoma
(CML) –– Tuberculosis
• Hilar
• Rare among children and adolescents; median –– Tuberculosis
age of diagnosis 60–65 years –– Histoplasmosis
• Rate of CML increases in the 15–19 years –– Leukemia
age interval –– Lymphoma
• Associated with fusion of two genes: BCR –– Sarcoidosis
(on chromosome 22) and ABL1 (on chromo- • Axillary
some 9) resulting in BCR-ABL1 fusion gene –– Cat scratch disease
• BCR-ABL1 fusion results from specific –– Arm or chest infection
translocation known as Philadelphia chromo- –– Leukemia
some t(9;22) –– Lymphoma
• Treated with tyrosine kinase inhibitor • Abdominal
–– Malignancy
–– Mesenteric adenitis
Chronic Lymphocytic Leukemia (CLL) –– Infection
• Occipital
• Rare disease in childhood –– Scalp infections (tinea capitis, lice)
• Mature B-cell neoplasm –– Seborrhea
• 5 to 10% presenting with typical “B” symptoms
• Most patients are asymptomatic with abso- Clinical approach to lymphadenopathy
lute lymphocytosis noted on routine CBC • History
• Lymphadenopathy –– Associated systemic symptoms
• Hepatosplenomegaly • Age
• Skin involvement –– Lymph node enlargement in children less
–– Most commonly recognized, nonlymphoid than 5 years of age most likely infectious
tissue involved –– Histiocytosis can cause lymphadenopathy
• Other organs may be involved as well in children less than 3 years
–– Large lymph node in neonate most likely
related to congenital infection
Lymphadenopathy –– Likelihood of malignant lymphoma
increases in adolescents
Causes of lymphadenopathy according to • Location
location –– Supraclavicular lymphadenopathy is
• Cervical always abnormal, and the chances of
–– Oropharyngeal infections malignancy are high
–– Mycobacterial lymphadenitis • Size
–– Cat scratch disease –– Size of enlarged lymph node aids in deter-
–– Kawasaki disease mining the need for further evaluation
• Supraclavicular –– Normal size of lymph node depends on the
–– Right side—Malignancy or infection from lymph node region and age of child
mediastinum –– Normal lymph node size based on age and
–– Left side—Malignancy or infection from size:
abdomen ◦◦ < 1 month of age: < 1 cm
◦◦ > 1 month of age: odgkin Lymphoma

H
▪▪ Most regions: < 1 cm
▪▪ Epitrochlear region: < 0.5 cm • Malignant lymphoma
▪▪ Inguinal region: < 1.5 cm • 7% of childhood cancers
◦◦ Risk of malignancy increased in lymph • 1% of childhood cancer deaths
nodes > 2 cm • Incidence varies by age
◦◦ Malignancy can occur in smaller nodes –– 1 per million for 0–4 years
• Characteristics –– 3.5 per million for 5–9 years
–– Consistency –– 10 per million for 10–14 years
◦◦ Fluctuance indicates infection –– 29 per million for 15–19 years
◦◦ Hard, fibrotic nodes are due to malig- • Bimodal peaks of incidence from 15 to
nancy or previous inflammation 34 years and older than 55 years
◦◦ Firm, rubbery nodes may indicate lym- • Infectious agents may be involved
phoma or leukemia –– EBV
▪▪ Nodes in acute leukemia tend to be –– HHV6
softer –– Cytomegalovirus
–– Fixation • Reed–Sternberg cell is the hallmark of HL
◦◦ Normal lymph nodes are freely mobile (Fig. 10.16)
◦◦ Abnormal lymph nodes become fixed/
nonmobile Clinical presentation
–– Tenderness • Painless lymphadenopathy
◦◦ Suggest recent, rapid enlargement, –– Cervical, supraclavicular, axillary, or
resulting in tension in pain receptors in inguinal
capsule
◦◦ Occurs with inflammatory processes,
immunologic stimulation, and
malignancy
Biopsy criteria
• Size
–– 2 cm
–– Increasing over 2 weeks
–– No decrease after 4 weeks
• Location
–– Supraclavicular
• Consistency
–– Hard
–– Matted
–– Rubbery
• Associated features
–– Abnormal chest x-ray
–– Fever Fig. 10.16 Hodgkin lymphoma presents as a localized or
–– Weight loss regional lymphadenopathy. The characteristic cell is the
–– Hepatosplenomegaly Reed–Sternberg cell (arrow)
• Mediastinal mass • Patients who relapse > 12 months after che-

–– May result in dysphagia, dyspnea, cough, motherapy alone or combined modality have
stridor, airway obstruction, or superior good retrieval response
vena cava (SVC) syndrome
• Pleural effusion
• Pericardial effusion Non-Hodgkin Lymphoma
• Bone marrow infiltration • 60% of all lymphomas in children
• Systemic symptoms/B symptoms • Median age at diagnosis is 10 years
–– Fever –– Incidence increases with age
–– Unintentional weight loss > 10% of body • Burkitt lymphoma is the most common
weight within 6 months prior to • Most children have de novo disease with no
diagnosis underlying condition
–– Night sweats • Related diseases
–– Severe combined immunodeficiency (SCID)
Diagnosis –– Wiskott–Aldrich syndrome
• Chest radiograph –– Ataxia telangiectasia
• CT chest, abdomen, and pelvis –– Bloom syndrome
• Positron emission tomography (PET) scan –– HIV
• Excisional biopsy of lymph node –– EBV
• CBC, comprehensive metabolic panel (CMP),
liver function test (LFT), lactate dehydroge- Clinical presentation
nase (LDH), erythrocyte sedimentation rate • Rapidly growing tumors with symptoms
(ESR) based on size and location
• Bone marrow aspirate and biopsy only for • Burkitt lymphoma of the abdomen (sporadic
patients with advanced stage disease, B symp- type) more common in the United States
toms, or CBC concerning for bone marrow • Burkitt lymphoma of the head and neck
involvement (endemic type) more common in Africa
• SVC syndrome—chest involvement
Treatment • Intestinal obstruction—abdominal mass
• Chemotherapy and radiation therapy are very • Paraplegia with spinal cord involvement
effective • Tumor lysis syndrome
• Chemotherapy regimens –– Hyperkalemia, hyperuricemia, hyperphos-
–– COPP (cyclophosphamide vincristine, pro- phatemia, hypocalcemia
carbazine, and prednisone)
–– ABVD (Adriamycin [generic: doxorubi- Diagnosis
cin], bleomycin, vinblastine, and • Chest radiograph
dacarbazine) • CT abdomen and pelvis
• CBC, CMP, Mg, Phos, uric acid, LDH
Prognosis • EBV
• Early-stage disease has event-free survival of
85–90% and overall survival at 5 years of Biopsy
95% • Classic “starry sky” appearance of Burkitt
• Poor prognostic factors lymphoma (Fig. 10.17)
–– Bulky tumor
–– Advanced stage at diagnosis Treatment
–– B symptoms • Chemotherapy
–– Oral mucosa
–– Lung
–– CNS
• Common symptoms
–– Bone pain
–– Soft tissue swelling
–– Skin rash
• Less common presentation
–– Diabetes insipidus
–– Respiratory insufficiency
–– Cytopenia
–– Lymphadenopathy
–– Liver dysfunction
–– Organomegaly
Fig. 10.17 Classic “starry sky” appearance of Burkitt lym- Diagnosis

phoma. The stars are actually macrophages that are phagocy- • Biopsy
tosing apoptotic Burkitt cells. This example presented as a • Skeletal survey
colonic mass with intussusception
• Chest radiograph
Prognosis • CBC, CMP, LFT, ESR, coagulation studies
• Excellent in most children • Abdominal ultrasound
• 90 to 100% survival rate with localized disease –– Assess size and structure of liver and spleen
–– Abdominal lymph nodes
Langerhans Cell Histiocytosis Additional testing based on clinical presentation

• Polyuria and polydipsia
• Rare histiocytic disorder –– Early morning urine specific gravity (SG)
• Characterized by single or multiple osteolytic and osmolality
bone lesions with histiocytic infiltration – – MRI brain
• Most common in children ages 1–3 years –– Water deprivation test
• Craniofacial bone involvement
Clinical presentation –– MRI head
• Varies based on location and extent of • Vertebral lesions
involvement –– MRI spine
• Limited to one organ in over half of patients • Diarrhea, failure to thrive, or malabsorption
–– Remainder of patients with multisystem –– Endoscopy
disease
Treatment
• Areas of involvement in order of decreasing
• Based on clinical findings
frequency
• Observation
–– Bone
• Surgery
–– Skin
• Chemotherapy
–– Lymph node
–– Liver Prognosis
–– Spleen • Excellent for patients with localized disease
Table 10.5 Chemotherapeutic agents and side effects –– Thyroid carcinoma

Chemotherapeutic agent Side effect –– (Terrible) lymphoma
Cyclophosphamide Hemorrhagic cystitis • Treatment
Ifosfamide Myelosuppression –– Treat underlying condition
Cisplatin Hearing loss
Carboplatin Peripheral neuropathy
–– Steroids and radiation in emergency setting
Bleomycin Pulmonary fibrosis
Doxorubicin Cardiac toxicity
Vincristine/vinblastine Peripheral neuropathy Superior Vena Cava Syndrome
Methotrexate Myelosuppression
Mucositis • Due to extrinsic compression of SVC by
Fluorouracil Myelosuppression anterior mediastinal mass
Mercaptopurine Myelosuppression
Etoposide Infusional hypotension • Signs and symptoms:
Secondary malignancy –– Plethora/red face
–– Facial swelling
–– Upper extremity edema
• Significant morbidity and mortality for –– Distended neck veins
patients with multisystem disease –– Neurologic symptoms (when severe)
Chemotherapeutic agents and side effects

(Table 10.5) Tumor Lysis Syndrome
• Secondary to rapid lysis of tumor cells with
ONCOLOGIC EMERGENCIES high tumor burden
• Most common with:
Spinal Cord Compression –– Initiation of chemotherapy
–– Large tumors
• Tumor in or around spinal cord –– Lymphoma
• Neurologic symptoms –– Leukemia
• Bowel or bladder dysfunction
• Treat with steroids and/or radiation Laboratory
• Hyperuricemia, hyperkalemia, hyperphos-
phatemia, hypocalcemia
Mediastinal Mass
Complications
• Respiratory distress • Cardiac dysrhythmia
–– Particularly when supine • Sudden death
• Cannot intubate because airway compression • Seizure
is below the vocal cords • Neuromuscular irritability
• Cannot maintain oxygenation and ventilation • Acute kidney injury and failure
when anesthetized Treatment
• Obtain chest radiograph with suspicion/diag- • Hydration
nosis of malignancy to evaluate for mediasti- • Allopurinol
nal mass • Rasburicase
• Tumors associated with mediastinal mass – –– High uric acid burden
“four T’s” • Continuous venovenous hemofiltration
–– Thymoma (CVVH)
–– Teratoma –– Acute kidney failure
BRAIN TUMORS Pilocytic Astrocytoma
• Account for almost 20% of all pediatric

cancers
• Peak age 0–4 years
• Based on location, size, growth rate, and age
• Increased intracranial pressure
–– Headache
◦◦ Persistent vomiting (often mornings)
–– Mental changes, irritability
–– Visual disturbances
◦◦ Diplopia
◦◦ Papilledema Fig. 10.18 Pilocytic astrocytoma is composed of bipolar
◦◦ Parinaud syndrome (often associated cells with frequent microcystic spaces. Juvenile pilocytic
astrocytoma is the most common childhood primary brain
with pineoblastoma) tumor
–– Gait disturbances and ataxia
• Failure to thrive Astrocytoma
• Cranial nerve abnormalities
• Focal neurologic deficits • Accounts for 40% of all CNS tumors
• Seizures • Juvenile pilocytic astrocytoma (JPA)—most
• Declining school performance common subtype in children (Fig. 10.18)
• Loss of developmental milestones
Location = Posterior fossa
• Classic site for JPA is cerebellum but can
Pathologic diagnosis = Based on cell occur anywhere in CNS
of origin Can occur at multiple Treatment
locations in the CNS • Surgery—primary treatment
• Chemotherapy
• Infratentorial/posterior fossa—60% • Radiation therapy
–– Pilocytic astrocytoma
–– Medulloblastoma
–– Ependymoma edulloblastoma
M
–– Atypical teratoid /rhabdoid tumor (AT/RT)
–– Diffuse intrinsic pontine gliomas (DIPG) • The most common malignant brain tumor in
• Supratentorial—40% children
–– Low-grade glioma • Accounts for 20% of all brain tumors (second
–– High-grade glioma most common)
–– CNS embryonal tumor and variants • 90% of embryonal tumors
(“PNET”)
Location = Arises in cerebellum and fourth
–– AT/RT
ventricle
–– Ependymoma
• May metastasize down the spinal cord and
–– Choroid plexus tumors
rarely outside CNS
Medulloblastoma Location = Suprasellar
Imaging = Solid and cystic components
Pineoblastoma
• PNET
yndromes Associated with Brain

S
Fig. 10.19 Medulloblastoma (40 ×) is a so-called “small Tumors
round blue” cell tumor of childhood. Medulloblastoma is a
posterior fossa tumor and the second most common brain • Neurofibromatosis (NF) type 1: Optic gli-
tumor of childhood oma, astrocytoma, neurofibroma, malignant
nerve sheath tumor
• NF type 2: Vestibular schwannomas, menin-
Histology = Cell type similar to primitive neu-
giomas, spinal cord ependymoma, spinal cord
roectodermal tumor (PNET) (Fig. 10.19)
astrocytoma
Treatment • Tuberous sclerosis
• Surgery—prognosis based on extent of • Von Hippel–Lindau: Hemangioblastoma,
resection angiomatosis, pheochromocytoma, renal cell
• Chemotherapy carcinoma, pancreatic cyst
• Radiation therapy • Li–Fraumeni: Association with p53 muta-
tion, astrocytoma, breast cancer, leukemias,
brain tumors
• Cowden syndrome: Multiple hamartomas
Ependymoma including the brain; dysplastic gangliocytoma
• Derived from the ependymal lining of the of the cerebellum
ventricles • Turcot syndrome: Medulloblastoma and
colon polyps
Location = 70% occur in the posterior fossa
Treatment OTHER TUMORS
• Maximally safe surgical resection
• Radiation Hepatoblastoma
• Children < 3 years
Craniopharyngioma • Can be congenital
• 90% occur by age of 5 years, 70% by age 2
• Account for 7–10% of childhood brain tumors
years
(most common benign brain tumor in
• Male predominance
children)
• Prevalence 1 per 1 million children
• Associated with panhypopituitarism and
visual loss (both due to the tumor itself and Associated syndromes/risk factors
treatment-related) • Familial adenomatous polyposis and Gardner
syndrome (APC gene mutations)
• Glycogen storage disease Clinical presentation

• Beckwith–Wiedemann syndrome • Ovarian = Abdominal pain, palpable mass
• Hemihypertrophy syndromes • Testicular = Irregular, nontender mass
• Li–Fraumeni syndrome (TP53) • Extragonadal = Depending on location
• Wilms tumor
• Low birth weight infants Diagnosis
• CT/MRI, metastatic workup (bone scan, chest
Clinical presentation CT)
• Large asymptomatic mass
• Weight loss, anorexia, vomiting, or abdomi- Laboratory
nal pain • AFP and/or human chorionic gonadotropin
• Right lobe more common (hCG)
• Metastasis most commonly to lungs
Treatment
Diagnosis • Surgery +/− chemotherapy depending on risk
• Laboratory: group and staging
–– Elevated alpha-fetoprotein (AFP)
–– Anemia and thrombocytosis are common
–– Bilirubin and liver enzymes are usually Neuroblastoma
normal
Malignancy originating from neural crest cells of
–– Hepatitis B and C serologies (usually
the sympathetic nervous system
negative)
• Imaging: Ultrasound, Abdominal X-ray
(KUB), CT, and/or MRI Epidemiology
• Biopsy • Third most common pediatric cancer overall
• Staging based on radiographic criteria • Most common extracranial solid tumor in
(PRETEXT grouping and grade) and surgical children
resection • 8% of childhood malignancy
• Most commonly diagnosed neoplasm in
Treatment infants (28–39% of neonatal malignancies)
• Chemotherapy • Mean age is 2 years
• Tumor resection
• Liver transplant for unresectable disease Clinical presentation
• Symptoms based on mass location
• Most cases arise in abdomen
Germ Cell Tumors –– Abdominal pain
–– Distended abdomen, palpable mass
• Bimodal age distribution (< 3 and adolescent) –– Hypertension (due to renal artery compres-
• Types based on histology: sion and catecholamine release)
–– Germinoma –– Urinary tract infections (due to the obstruct-
◦◦ Dysgerminoma ing abdominal mass)
◦◦ Seminoma –– Neck mass
–– Yolk sac tumor –– Thoracic tumors
–– Mixed germ cell tumor ◦◦ Horner syndrome
–– Teratoma (benign) –– Spinal tumors
◦◦ Paraplegias
–– Metastatic disease ◦◦ DNA hyperdiploidy (if less than 1 year

◦◦ Bone pain (bone metastases) of age)
◦◦ Cytopenias (bone marrow infiltrate) Treatment
◦◦ Orbital proptosis and ecchymosis— • Observation only for some low-risk groups
“raccoon eyes” (retro-orbital soft tissue • Surgery
infiltrate) • Chemotherapy
◦◦ Bluish subcutaneous nodules (skin • Radiation therapy
infiltrate) • Stem cell transplant
◦◦ Fever/irritability • New vaccines/antibodies
◦◦ Failure to thrive • Retinoic acid
• Paraneoplastic symptoms
–– Secretory diarrhea
–– Increased sweating Wilms Tumor (Nephroblastoma)
–– Opsoclonus, myoclonus (“dancing eyes
and dancing feet”)
WT-1 gene located on 11p13
Diagnosis (Fig. 10.20)
• CT/MRI (often see calcifications)
Epidemiology
• MIBG imaging
• Peak incidence 2–5 years of age, and more
• Bone marrow biopsy
common in African American children
• Tumor markers
• 7 cases/million children
–– Elevated urine homovanillic acid (HVA),
vanillylmandelic acid (VMA) Clinical presentation
• Biopsy • Abdominal mass often noted first by parents
–– Poor prognostic factors on pathology: • Abdominal pain, vomiting, hematuria in
◦◦ N-myc proto-oncogene (MYCN) 12–25%
amplification • Hypertension
• Hematuria
Neuroblastoma • Anomalies and syndromes associated with
Wilms tumor
–– Beckwith–Wiedemann syndrome (hemi-
hypertrophy, organomegaly, macroglossia,
omphalocele), loss of imprinting at 11p15
–– WAGR (Wilms, aniridia, genitourinary
abnormalities, mental retardation), del 11p13
–– Denys–Drash syndrome (early-onset renal
failure with renal mesangial sclerosis, male
pseudohermaphroditism), germline WT1
mutation
–– Perlman syndrome (fetal gigantism, mac-
rocephaly and macrosomia, renal
hamartomas)
Fig. 10.20 Neuroblastoma is one of the “small round blue”
cell tumors of childhood. A majority are at least poorly dif- Diagnosis (Fig. 10.21)
ferentiated with the presence of some neuropil (black arrow) • US, KUB, CT, and/or MRI
often in association with Homer-Wright rosettes (10 ×)
• Urinalysis –– Large tumor > 500 g

• Pathology –– Unfavorable histologic type (anaplasia)
Treatment –– Advanced stage (III or IV)
• Surgery (upfront vs. after neoadjuvant
chemotherapy)
• Chemotherapy and radiotherapy, depending R habdomyosarcoma
on the histology and staging
• Overall cure rate for nephroblastoma is Epidemiology
approximately 90%; it varies with the clinical • Most common soft tissue sarcoma
and pathological features of the disease • Increased frequency with neurofibromatosis
• Poor prognostic factors: • Peak incidence 1–5 years and 15–19 years
• 10% occur in the first year of life
Wilms’ Tumor • 70% appear within the first decade
• Anatomic distribution
–– Head and neck—40%
–– Genitourinary—20%
–– Trunk—10%
–– Retroperitoneal and others
◦◦ Metastases to lung, bone marrow, lymph
nodes, and bone. Metastases to brain and
liver more common in relapse setting
• Specific histologic types:
–– Embryonal: 60%, intermediate prognosis
–– Alveolar type: 15%, most in the trunk and
extremities; poor prognosis (Fig. 10.22)
–– Botryoid type: 6%, “bunch of grapes”;
most in the vagina, uterus, bladder, naso-
Fig. 10.21 Wilms tumor is a triphasic tumor composed of
blastemal (black arrow), epithelial (arrowhead), and mesen- pharynx, and middle ear; good prognosis
chymal components (red arrow). Most are diagnosed before –– Pleomorphic form: 1%, adult type
6 years of age
Fig. 10.22 At low Rhabdomyosarcoma

power (10 ×), alveolar
rhabdomyosarcoma has a
vaguely alveolar growth
pattern with neoplastic
cells lining thin fibrous
septae. At higher power,
pink cytoplasmic material
is evident (arrows)
showing early myogenic
differentiation
Treatment consult should be considered, and appropri-

• Surgery, chemotherapy, and radiation ate imaging performed in conjunction with
respiratory care.
• Oncologic emergencies are true emergencies
PEARLS AND PITFALLS and cannot wait until the next day or the next
week.
• If a patient is iron deficient, electrophoresis • Within a few hours of recognizing that a child
may not demonstrate if they also have a thal- could have a condition resulting in an onco-
assemia trait (high A2). If there is a concern, logic emergency (severe pancytopenia, sig-
it is recommended that hemoglobin electro- nificant leukocytosis with thrombocytopenia
phoresis should be repeated once the patient or anemia), the child should be referred to an
is no longer iron deficient. oncologic specialist or an appropriate emer-
• All patients with SCD should be followed by gency room.
a hematologist, and their medication manage- • Malignancy should be in the differential for
ment (hydroxyurea, glutamine) should be children who are not achieving their appro-
guided by the hematologist. priate milestones or who are not gaining
• Pancytopenia can occur with any viral syn- weight, because some children with brain
drome, especially in a young child, but would tumors present mainly with a delay in achiev-
still warrant an evaluation by a hematologist/ ing milestones.
oncologist. • Significant back pain or continued leg or
• Children who have significant and unex- extremity pain in a child is not normal and
plained bleeding after surgeries or dental should be evaluated by an oncologist. It is not
extractions and who require more treatment advised to place children on neuropathic
than is usual for such procedures (nasal pack- agents or prolonged opioids prior to a full
ing, repeat surgeries), or who develop acute evaluation by oncology specialists.
anemia, should be assessed for an underlying
bleeding disorder. Acknowledgment The authors gratefully
• Male patients who have swelling of their acknowledge the contributions of Staci Bryson,
joints when starting to ambulate should have MD, and Arlynn F. Mulne, MD, Department of
a factor deficiency high on the differential Pediatrics, Paul L. Foster School of Medicine,
and be referred to a hematologist. Texas Tech University Health Sciences Center, El
• Consultation with a hematologist regarding Paso, Texas, USA, to the 1st edition of this chap-
how to administer vaccines is recommended ter, from which some images and tables have been
in those patients with a known bleeding incorporated into this edition as well.
disorder.
• ITP is a very common disorder; patients who
have ITP caused by vaccines should still be References
rechallenged with those vaccines in the
future. 1. Kliegman R, Stanton B, St. Geme JW III, Schor
• Children that present with acute and severe NF, Behrman RE, editors. Nelson textbook of
shortness of breath without a history of atopy, pediatrics. Philadelphia: Elsevier; 2016.
asthma, or allergies should not be given pred- 2. Loghavi S, Hasserjian RP. Cytopenias: reactive
nisone without considering the possibility of and neoplastic. In: Wang SA, Hasserjian RP, edi-
a mediastinal mass. While it is necessary to tors. Diagnosis of blood and bone marrow disor-
stabilize the airway, a hematology/oncology ders. Cham: Springer International. p. 17–80.
3. Rogers HJ. Normal bone marrow. In: George TI, Buitenkamp TD, Izraeli S, Zimmermann M,
Arber DA, editors. Atlas of bone marrow pathol- Forestier E, Heerema NA, van den Heuvel-
ogy. New York: Science+Business Media; 2018. Eibrink MM, et al. Acute lymphoblastic leu-
4. Schafernak KT, Calvo KR. Constitutional, kemia in children with Down Syndrome: a
metabolic, and related disorders. In: George TI, retrospective analysis from the Ponte Di Legno
Arber DA, editors. Atlas of bone marrow pathol- study group. Blood. 2014;123(1):70–7.
ogy. New York: Science+Business Media; 2018. Camaschella C. Iron-deficiency anemia. N Engl J
p. 33–66. Med. 2015;372(19):1832–43.
5. Penanchansky L. Pediatric bone marrow. Berlin: DeLoughery T. Microcytic anemia. New Engl J
Springer; 2004. Med. 2014;371(14):1324–31.
Haupt R, Minkov M, Astigarraga I, Schäfer E,
Nanduri V, Jubran R, Euro Histio Network,
Suggested Reading et al. Langerhans cell histiocytosis (LCH):
guidelines for diagnosis, clinical work-up, and
Adams M, Jenney M, Lazarou L, White R, Birdsall treatment for patients till the age of 18 years.
S, Staab T, et al. Acute myeloid leukaemia after Pediatr Blood Cancer. 2013;60(2):175–84.
treatment for acute lymphoblastic leukaemia in Horton TM, Steuber CP, Aster JC. Park JR, edi-
girl with Bloomsyndrome. J Genet Syndr Gene tor. Overview of the clinical presentation and
Ther. 2013;4(8). pii: 1000177. diagnosis of acute lymphoblastic leukemia/
Adams RJ, McKie VC, Hsu L, Files B, Vichinsky lymphoma in children. Waltham: UpToDate.
E, Pegelow C, et al. Prevention of a first stroke http://www.uptodate.com. Accessed 24 Dec
by transfusions in children with sickle cell 2018.
anemia and abnormal results on transcra- Karimi M. Guidelines for diagnosis and manage-
nial Doppler ultrasonography. N Engl J Med. ment of Beta-thalassemia intermedia. Pediatr
1998;339(1):5–11. Hematol Oncol. 2014–10;31:583–96.
Adams RJ, Brambilla D, Optimizing Primary Kliegman R, Stanton B, St. Geme JW III, Schor
Stroke Prevention in Sickle Cell Anemia NF, Behrman RE, editors. Nelson textbook of
(STOP 2) Trial Investigators. Discontinuing pediatrics. Philadelphia: Elsevier; 2016.
prophylactic transfusions used to prevent Levin TL, Mäkitie O, Berdon WE, Lachman
stroke in sickle cell disease. N Engl J Med. RS. Shwachman–Bodian–Diamond Syndrome:
2005;353(26):2769–78. metaphyseal chondrodysplasia in children
Adams RJ, McKie VC, Hsu L, Files B, Vichinsky with pancreatic insufficiency and neutropenia.
E, Pegelow C, et al. Prevention of a first stroke Pediatr Radiol. 2015;45(7):1066–71. Review.
by transfusions in children with sickle cell Lipton JM. Evaluation of pancytopenia. BMJ Best
anemia and abnormal results on transcra- Practice (database). 2018. https://bestpractice.
nial Doppler ultrasonography. N Engl J Med. bmj.com/topics/en-us/1024. Accessed 24 Dec
1998;339(1):5–11. 2018.
Bain B. Diagnosis from the blood smear. N Engl J McClain KL. Kaplan SL, Mahoney Jr DH, Drutz
Med. 2005;353(5):498–507. JE, editors. Peripheral lymphadenopathy in
Bolton-Maggs PH, Langer JC, Iolascon A, children: evaluation and diagnostic approach.
Tittensor P, King MJ, General Haematology Task Waltham: UpToDate. http://www.uptodate.com.
Force of the British Committee for Standards in Accessed 24 Dec 2018.
Haematology. Guidelines for the diagnosis and Medeiros LJ, Greiner TC. Hodgkin’s disease.
management of hereditary spherocytosis – 2011 Cancer. 1995;75(1 Suppl):357–69.
update. Br J Haematol. 2012;156(1):37–49. Nathan DG, Oski FA, Orkin SH, editors. Nathan
and Oski’s hematology and oncology of infancy
and childhood, vol. 2. Philadelphia: Elsevier sis, risk-stratification, and management. Am J

Saunders; 2015. Hematol. 2017;92(1):94–108.
Rabin KR, Whitlock JA. Malignancy in children Van Etten RA. Larson RA, editor. Clinical mani-
with trisomy 21. Oncologist. 2009;14(2):164–73. festations and diagnosis of chronic myeloid
Rai KR, Stilgenbauer S, Aster JC. Larson RA, edi- leukemia. Waltham: UpToDate. http://www.
tor. Clinical features and diagnosis of chronic uptodate.com. Accessed 24 Dec 2018
lymphocytic leukemia/small lymphocytic lym- Vannucchi AM. How I treat polycythemia vera.
phoma. Waltham: UpToDate Inc. http://www. Blood. 2014;124(22):3212–20.
uptodate.com. Accessed 24 Dec 2018. Wang WC, Ware RE, Miller ST, Iyer RV, Casella
Schrier SL. Mahoney Jr DH, editor. Acquired JF, Minniti CP, BABY HUG Investigators, et al.
aplastic anemia in children and adolescents. Hydroxycarbamide in very young children
Waltham: UpToDate. http://www.uptodate.com with sickle-cell anaemia: a multicentre, ran-
(Accessed 24 Dec 2018 domised, controlled trial (BABY HUG). Lancet.
Tefferi A, Barbui T. Polycythemia vera and essen- 2011;377(9778):1663–72.
tial thrombocythemia: 2017 update on diagno-
Allergy and Immunology
11
ALLERGY Types of hypersensitivity (Table 11.1)
Introduction llergic Rhinitis (AR)

A
• Allergic disorders are very common in chil-
dren and include a variety of conditions such Background
as asthma, allergic rhinitis, atopic dermatitis, • Allergic rhinitis (AR) is the most common
and food allergies chronic disease in children
• There is a strong familial predisposition for • Often mistaken for recurrent episodes of the
allergic disease, but environmental exposures common cold
(i.e., air pollution, cigarette smoke), diet, and • At difference to the common cold, AR usu-
concomitant infection also play an important ally does not present with low-grade fevers or
role in the incidence and severity of atopy in malaise. Nasal and eye pruritus also distin-
children guish AR from viral upper respiratory
• Respiratory and food allergies are by far the infections
most prevalent allergic disorders in the pedi- • AR is one of the major reasons for visits to
atric age, but children can also suffer from pediatricians and is associated with a number
drug and insect venom hypersensitivity of significant comorbidities, including
asthma, sinusitis, and ear infections
Allergy or type 1 hypersensitivity is mediated
by immunoglobulin E (IgE) Implicated allergens
• Sensitization, that is, the ability to make IgE • Pollens, molds, dust mites, and animal dander
in response to a particular allergen, is the pre- are the most common causative allergens
requisite for the development of allergic • Tree pollens are highest in the spring, grass
disease pollens in the early summer, and weeds in the
• Yet, sensitization does not always lead to fall—all important causes of seasonal or out-
clinical manifestations. In other words, one door allergies.
may be able to detect IgE to peanuts in indi- • Molds are high all year round and may cause
viduals who eat peanuts regularly with no persistent allergies or indoor allergies, e.g.,
problems Alternaria and Cladosporium in warmer sea-
sons and Penicillium and Aspergillus in the
M. I. Garcia Lloret (*) · C. Y. Kuo colder seasons. Molds are an important cause
Division of Pediatric Allergy/Immunology and Rheumatology, of asthma exacerbations
Department of Pediatrics, UCLA School of Medicine,
Los Angeles, CA, USA
e-mail: migarcia@mednet.ucla.edu

392 M. I. Garcia Lloret and C. Y. Kuo
Table 11.1 Types of hypersensitivity

Types of
hypersensitivity Examples Mediators Description
Type I: allergy Anaphylaxis IgE Reaction occurs in minutes
(immediate) Allergic Antigens cross-link the IgE on mast cells and basophils →
rhinoconjunctivitis release of histamine and other mediators
Testing: Skin test for specific IgE
Type II: cytotoxic, Drug-induced IgM or IgG Antibody (IgM or IgG) binds to cell surface antigens →
antibody-dependent hemolytic anemia complement fixation → cellular destruction via the MAC
Complement Testing: direct and indirect Coombs test
MAC
Type III: immune Serum sickness IgG Circulating immune complexes → deposit in postcapillary
complex disease Lupus Complement venules → local inflammatory reaction
PSGN Neutrophils
Type IV: delayed-type Contact dermatitis T-cell Mediated by T-cells rather than by antibodies
hypersensitivity TB skin test Cellular response usually appears 48–72 h after antigen
Chronic transplant exposure
rejection
IgE immunoglobulin E, MAC membrane attack complex, PSGN poststreptococcal glomerulonephritis, TB tuberculosis
• Dog and cat dander are abundant in indoor • Comorbid conditions such as headaches,
settings and a common cause of perennial sleep disturbance, fatigue, and impaired con-
allergic rhinitis and asthma centration and attentiveness at school
• Dust mites are another prevalent indoor aller- • Nasal turbinates may appear edematous, with
gen, is a very important trigger of perennial a pale to bluish hue
asthma and allergies • Cobblestoning from lymphoid hyperplasia
may be seen on the posterior oropharynx
Classification • Dark discolorations underneath the eyes,
• Intermittent disease with symptoms < 4 days/ “allergic shiners,” are due to venous engorge-
week or for a duration of < 4 weeks, usually ment and suborbital edema
related to outdoor allergens, e.g., pollens • Dennie–Morgan lines are folds under the eyes
• Persistent disease with symptoms > 4 days/ due to edema
week and are present for > 4 weeks, usually • A transverse nasal crease is seen across the
related to indoor allergens, e.g., molds bridge of the nose in children who chroni-
cally push their palms upward under their
Clinical presentation noses (“allergic salute”; Fig. 11.1)
• Nasal congestion may be reported by parents • Tonsils and adenoids are frequently enlarged
as mouth breathing, snoring, or a nasal voice in young patients with chronic rhinitis and
• Paroxysmal sneezing, nasal and palatal pruri- can be an additional cause of mouth breath-
tus, nose blowing, sniffing, snorting, and ing, snoring, and, in severe cases, sleep apnea
occasional coughing • Chronic mouth breathing from nasal obstruc-
• Nasal pruritus often produces the classic sign tion may cause allergic facies, with an open
of the allergic salute mouth, receding chin, overbite, elongated
• Itchy eyes and postnasal drip face, and arched hard palate
• Seasonality, progression of symptoms, identi- • Allergic conjunctivitis usually presents with
fiable triggers, alleviating factors, and respon- excessive tearing, conjunctival injection, and
siveness to allergy medication rubbing of the eyes
11 Allergy and Immunology 393
–– Use dust mite covers on the bed and

pillows
–– Use hypoallergenic pillows and
comforters
–– Wash linens in hot water to denature dust
mite allergen
–– If allergic to pets, getting rid of them
entirely or removing them from the bed-
room may help decrease exposure to pet
danders
–– A size-appropriate HEPA filter placed in
the bedroom may also help decrease expo-
sure to cat dander while removing indoor
air pollutants
Fig. 11.1 Child with allergic rhinitis showing the transverse • Intranasal corticosteroids (INS)
nasal crease across the bridge of the nose
–– The first-line treatment and most effective
Diagnosis –– Onset of action has been shown to be
• History and physical examination are key to within 12 h
diagnosis –– Can be used as needed, but far more effec-
• Percutaneous (prick or puncture) skin testing tive if used long term
remains the most specific and cost-effective –– Epistaxis is the most common side effect
diagnostic modality –– Generally have no effect on growth over
• Serum detection of allergen-specific IgE by 1 year of treatment in pediatric patients
enzyme- linked immunosorbent assay • H1 antihistamine
(ELISA) also may be used –– The most popular
• These tests can help to identify the offending –– Decreases sneezing, itching, and rhinor-
allergen, and specific avoidance can be rhea, but oral antihistamines are notori-
recommended ously ineffective in treating nasal
• Nasal smear for eosinophils with eosinophil congestion
count of greater than 4% in children may help –– Adverse effects include sedation, which
distinguish AR from viral infections and non- can lead to reduced school and cognitive
allergic rhinitis performance
–– Sedation effect can be avoided by using
Management second-generation antihistamines that have
• Allergen avoidance, whenever possible low or no sedation effect
• Intermittent disease (outdoor environmental • Decongestants
control) –– Long-term use of oral decongestants, in
–– Staying inside (5–10 a.m.) general, is not recommended because of
–– Keep air-conditioning on during the spring, potential side effects that include palpita-
fall, and pollen seasons tions, tachycardia, and insomnia
• Persistent disease (indoor environmental –– Prolonged use of topical decongestant can
control) lead to rhinitis medicamentosa (rebound
–– Avoiding molds includes humidity control nasal congestion)
< 51% in the home by using a • Leukotriene receptor antagonists (LTRA)
dehumidifier such as montelukast can be used
• Allergy immunotherapy
–– It is not used routinely for management of
mild-to-moderate AR that is responsive to
medical treatment
–– Reserved for more severe cases and in
those in which allergen avoidance is not
desired or possible (e.g., pet ownership)
• Comorbidities
–– AR also is one of the risk factors associ-
ated with otitis media
–– 20% of children with AR have otitis media
with effusion; 50% of the children who
have chronic otitis media with effusion
have AR Fig. 11.2 18-month-old child with pruritic circumscribed
–– Poorly controlled rhinitis symptoms may and coalescent wheals
exacerbate coexisting asthma and is an
important cofactor in asthma exacerbations –– Caused primarily by insect bite-induced
–– AR may increase the risk of developing hypersensitivity
sinusitis –– Clusters on exposed areas of skin, sparing
the genital, perianal, and axillary regions
–– Prevalence of papular urticaria peaks in
children from the ages of 2–10 years
URTICARIA • Erythema multiforme
–– Lesions may resemble urticaria and may
Background
be triggered by the same etiologic agents
• Urticaria is a rash that consists of pruritic,
such as infections and medications
blanching, erythematous, circumscribed, or
–– Erythema multiforme is distinguished from
(often) coalescent wheals
urticaria by the targetoid appearance of the
• Acute urticaria < 6 weeks
lesions
• Chronic urticaria 6 weeks or more
–– Patients who have erythema multiforme are
Causes at risk for developing mucosal and sys-
• Common allergens include food, medica- temic involvement
tions, insects, pollens, and animal dander • Urticaria pigmentosa (UP)
• Physical factors such as cold, pressure, heat,
Treatment
and light can trigger urticaria
• Identify and avoid the offending agent
• Another common cause of urticaria in children
• First-generation antihistamines (diphenhydr-
is infectious illness, especially from viruses
amine, hydroxyzine) are very effective but
Clinical presentation can lead to excessive sedation
• Wheals: Pruritic, blanching, erythematous, • Second-generation antihistamines (lorata-
circumscribed, or (often) coalescent wheals dine, cetirizine, and fexofenadine) are also
(Fig. 11.2) effective in controlling symptoms
• Use of glucocorticosteroids should be reserved
Differential diagnosis for children not responsive to H1- and
• Papular urticaria H2-antihistamines or children afflicted with
–– Common cause of papular, pruritic skin severe cases that involve significant
eruptions angioedema
• Another alternative medication for the treat- found for these illnesses even in asymptom-
ment of acute urticaria is leukotriene modifiers atic patients
such as montelukast, but with limited efficacy • Other reported infectious causes are viral
• If anaphylaxis, such as laryngeal angioedema, infections, urinary tract infections, and para-
respiratory, or gastrointestinal (GI) symp- sitic infections
toms, a self-injectable epinephrine pen should • Autoimmune diseases that have been associ-
be provided ated with chronic urticaria are thyroid disease,
celiac disease, type 1 diabetes mellitus, inflam-
matory bowel disease, juvenile idiopathic
Chronic Urticaria arthritis, and systemic lupus erythematosus
• The most common specific autoimmune asso-
Causes ciation with chronic urticaria is autoimmune
• Defined by urticarial lesions persisting or thyroid disease
recurring for more than 6 weeks • If evidence of vasculitis, referral for skin
• Physical factors are common triggers for biopsy may be indicated
chronic urticaria and can act alone or with
urticaria of other causes Treatment
• The main types of physical urticaria are der- • Very similar to acute urticaria
matographic, cholinergic, cold, pressure, • Specialists may use other therapies for chil-
solar, vibratory, and exercise-induced dren with chronic urticaria that has been
• Chronic infections, thyroid, and autoimmune refractory to standard therapies
disease are rare causes of chronic urticaria • Examples of these medications include
• Allergies rarely play a causal role and allergy hydroxychloroquine, sulfasalazine, dapsone,
testing in general is not indicated omalizumab, colchicine, mycophenolate
mofetil, and cyclosporine
Differential diagnosis • These medications require close monitoring
• Urticaria pigmentosa (UP) for adverse effects and should be used only
–– A form of cutaneous mastocytosis, usually by specialists experienced in prescribing
benign; can be associated with systemic these immune-modulating medications
mast cell activation
–– Lesions of UP are reddish brown macules
that wheal like a hive when stroked (posi-
tive Darier sign)
MASTOCYTOSIS
• Urticarial vasculitis
–– Rare in children but typically presents with Background
fever, arthralgia, and painful fixed urticar- • Disorder characterized by mast cell prolifera-
ial and petechial lesions that last longer tion and accumulation within various organs,
than 24 h most commonly the skin
–– Urticaria vasculitis is differentiated from • Cutaneous mastocytosis
typical chronic urticaria by the presence of –– Urticaria pigmentosa
nonpruritic, painful lesions with systemic • Systemic mastocytosis
symptoms
Diagnosis • Most patients have pruritic cutaneous
• Infection may be the cause for the urticaria lesions
• Positive serologic findings for Chlamydia • Macules, papules, nodules, plaques, blisters,
pneumoniae and Helicobacter pylori can be and bullae (Fig. 11.3)
• Plasma or urinary histamine level

• Elevated tryptase level
Treatment
• H1 and H2 antihistamines decrease pruritus,
flushing, and GI symptoms
• Cromolyn is a mast cell stabilizer that
improves diarrhea, flushing, headaches, vom-
iting, urticaria, abdominal pain, nausea, and
itching in some patients
• Epinephrine pens for cases of anaphylaxis
• Avoid triggers
Prognosis
• Most patients with urticaria pigmentosa (UP)
exhibit onset before age 2 years, which is
associated with an excellent prognosis, often
resolved by puberty
• Cutaneous mastocytosis onset after age
10 years portends a poorer prognosis, which
is associated more often with systemic dis-
ease, and carries a higher risk of malignant
transformation
Fig. 11.3 8-month-old girl with severe mastocytosis cuta-
neous type (urticaria pigmentosa) showing pruritic macules,
papules, blisters, and crusts all over the body HEREDITARY ANGIOEDEMA
• Face tends to be less affected (HAE)
• Darier sign: Wheal and surrounding erythema
develop in a lesion after rubbing it Background
• Some patients, especially those with extensive • HAE usually presents in childhood or adoles-
cutaneous disease, experience acute systemic cence with a mean age at onset between 8 and
symptoms exacerbated by certain activities or 12 years
ingestion of certain drugs or foods • Type 1 is secondary to insufficient levels of
• Possible systemic symptoms include flushing, C1 inhibitor
headache, dyspnea, wheezing, rhinorrhea, • Type 2 is associated with normal levels but
nausea, vomiting, diarrhea, and syncope dysfunctional C1 inhibitor
• Anaphylactic reactions to Hymenoptera • Type 3 has normal functional levels of C1
stings may be the first sign of mastocytosis inhibitor; this type is nonexistent in children
and adolescents
Diagnosis
• Complete blood count (CBC) in systemic Clinical presentation
mastocytosis may reveal anemia, thrombocy- • Recurrent, episodic, nonpruritic swelling of
topenia, thrombocytosis, leukocytosis, and the skin and mucosal tissues
eosinophilia
• Laryngeal edema that may lead to death by –– Attenuated androgens, such as danazol or
asphyxiation oxandrolone, and antifibrinolytics, such as
• Severe abdominal attacks manifested by tranexamic acid
intestinal edema
• The swelling can occur anywhere on the body,
including lips, eyelids, hands, feet, and ANAPHYLAXIS
genitals
• The swelling usually develops over the course
of 24 h and then resolves spontaneously in Background
the next 24–36 h • Anaphylaxis is an acute, life-threatening sys-
• Can be triggered by minor injury, dental temic reaction that results from the sudden
work, infection, stress, or menstruation release of mediators from mast cells and
• The frequency of the swelling is patient-spe- basophils
cific, occurring as frequently as once per • Prompt recognition of the signs and symp-
week or as rarely as once per year toms of anaphylaxis is critical to providing
• The disease is inherited, commonly in an rapid and effective treatment
autosomal-dominant fashion • Epinephrine is the most important medication
• If a diagnosis of HAE is made, testing of first- for treating anaphylaxis, and earlier adminis-
degree relatives is recommended tration portends a better prognosis
Diagnosis Causes
• The abdominal attacks may be mistaken for • Food
an acute abdominal condition such as appen- –– The most common cause of anaphylaxis in
dicitis or mechanical obstruction the outpatient setting is food
• The angioedema of HAE occurs without pru- –– Foods most commonly implicated are pea-
ritus or urticaria, develops more gradually nuts, tree nuts, fish, shellfish, cow’s milk,
over several hours, and is poorly responsive soy, egg, soy, and seeds
to antihistamines, corticosteroids, or • Medications
epinephrine –– Medications are the second most common
• The diagnosis of HAE is made by confirming cause of anaphylaxis in children
a deficiency in the C1 inhibitor, either quanti- –– The two most frequent culprits are antibi-
tatively or qualitatively otics, particularly β-lactam antibiotics, and
nonsteroidal anti- inflammatory drugs
Treatment (NSAIDs)
• Begins with immediate management of the • Radiographic contrast
patient’s airway if compromised –– Anaphylactoid reactions associated with
• Intubation may be necessary for the protec- radiographic contrast material occur in
tion of the airway if laryngeal edema is approximately 1% of patients
present –– Pretreatment with oral corticosteroids and
• In children with severe or frequent attacks antihistamines can reduce the risk of ana-
occurring more than once per month, long- phylactoid reactions from radiographic
term prophylaxis should be considered contrast material
–– Complement C1 esterase inhibitor can be • Stinging insects
used as an acute treatment, short or long- –– Hymenoptera: Stings by bees, vespids
term prophylaxis (yellow jackets, hornets, and wasps), and
stinging fire ants can cause anaphylaxis –– Subcutaneous allergen immunotherapy

and can be fatal (allergy shots) is another potential cause of
–– Cutaneous symptoms can be treated symp- anaphylaxis
tomatically with cold compresses, oral • Idiopathic
antihistamines, and oral analgesics
–– Systemic symptoms should prompt imme- Clinical presentation
diate administration of epinephrine and • Flushing, urticaria, pruritus, angioedema,
immediate evaluation in a local emergency cough, wheezing, stridor, dyspnea, abdomi-
department nal cramping, vomiting, diarrhea, dizziness,
• Latex and syncope
–– Natural rubber latex is an emerging cause • Absence of cutaneous symptoms argues
of anaphylaxis against anaphylaxis but cannot completely
–– Common in certain patients, e.g., patients rule it out
with spina bifida and bladder exstrophy • IgE-mediated allergic reactions triggered by
due to frequent exposure and sensitization foods typically occur rapidly and usually
• Vaccination within 1 h of ingestion
–– Anaphylaxis to vaccines is an exceedingly • Other adverse food reactions, such as food
rare but important cause of a life-threaten- poisoning, occur more slowly and may be
ing allergic reaction delayed by as much as 24 h from ingestion
–– A vaccine containing gelatin, egg, chicken, • 80% to 90% of cases of food-induced ana-
yeast, and neomycin can cause anaphylaxis phylaxis present with cutaneous findings of
–– Patients can undergo skin testing to the hives, angioedema, or both
components of the vaccine, such as gelatin, • Cutaneous findings are uncommon in food
and to the vaccine itself poisoning
• Exercise • A careful history from the patient, parent,
–– Exercise and physical exertion can lead to caregiver, or other witness is helpful in deter-
systemic mast cell mediator release, result- mining a potential trigger
ing in anaphylaxis
–– A few minutes of exercise can cause flush- Differential diagnosis
ing, pruritus, diffuse warmth, urticaria, and • Vasovagal or neurogenic syncope
fatigue • Vocal cord dysfunction
–– It may progress to angioedema, laryngeal • Asthma exacerbation
edema, GI symptoms, hypotension, or col- • Panic attack
lapse if exercise is continued • Isolated angioedema
–– Eating specific food 4–6 h before exercise • Food poisoning and other causes of shock
is a common co-trigger, as are alcohol or • Sepsis
NSAIDs • Cardiogenic shock
–– Taking medication before exercise by up to
Management
24 h may prevent food-exercise-induced
• A serum tryptase level taken within 6 h of a
anaphylaxis or medication-exercise-
suspected anaphylactic reaction may help
induced anaphylaxis
confirm the diagnosis in many cases
• Immunotherapy
• Referral to an allergist is warranted so that ◦◦ These cases can be given cephalosporin

skin tests, specific IgE in vitro testing, can be with no problem
done –– Penicillin reaction IgE-mediated
• Challenge tests may be considered for more ◦◦ Anaphylaxis
definitive diagnosis, especially in difficult ◦◦ Urticarial rash
cases ◦◦ First-generation cephalosporins in
• Epinephrine penicillin-
allergic patients is 3–7%,
–– The mainstay of short-term treatment for whereas the increased risk is negligible
anaphylaxis for third-generation cephalosporins
–– Aqueous epinephrine in a 1:1000 dilution –– Stevens–Johnson syndrome or toxic epi-
(0.01 mg/kg in children; maximum, 0.3 mg) dermal necrolysis associated with a partic-
–– Should be administered intramuscularly in ular medication
the outer aspect of the thigh every 5 min as ◦◦ Same drug and structurally related drugs
needed to control symptoms should be strictly avoided in the future
• Epinephrine pens
–– Self-administration epinephrine pens must
be carried for all patients at risk for FOOD ALLERGIES
anaphylaxis
–– For children under 30 kg, the dose is
0.15 mg Mechanism of food allergies
–– For children greater than or equal to 30 kg, • IgE-mediated
the dose is 0.3 mg –– The most common form, affecting about
• Diphenhydramine 8% of children in the United States
–– Second-line therapy • Non-IgE-mediated
–– 1 to 2 mg/kg every 6 h as needed –– Not so rare, includes disorders such as
• Ranitidine eosinophilic esophagitis (EoE), cow’s milk
–– Histamine-2 (H2)-receptor antagonists protein allergy, and food protein-induced
may be considered enterocolitis (FPIES)
–– 1 to 2 mg/kg • Most common triggers
• Inhaled beta-2 agonist, e.g., albuterol if –– Eggs, cow’s milk, peanuts, tree nuts, fish,
bronchospasm shellfish, soy, and wheat
• Glucocorticosteroids
–– It may not be helpful for short-term treat- Clinical presentation
ment but can be considered for prevention • Skin reactions, urticaria, or angioedema (80%)
of recurrent or protracted anaphylaxis • Atopic dermatitis (AD) is a frequent comorbid-
–– Oxygen therapy and intravenous (IV) fluid ity in patients with IgE-mediated food allergy
–– If hypoxia or hypotension • Nasal congestion, rhinorrhea, cough, wheeze
• Prevention • Abdominal pain, emesis, diarrhea
–– Avoid triggers or allergens • Anaphylaxis
–– Penicillin reaction non-IgE-mediated • In IgE-mediated food allergy, the onset of
◦◦ For example, vomiting, diarrhea, head- reaction is usually quick, from minutes to up
ache, or a nonurticarial, nonpruritic rash to 2 h
• Non-IgE-mediated reactions develop over Immune responses

time and can present as dysphagia (EoE), • Specific IgE hypersensitivity
delayed and protracted emesis (FPIES), and • IgG-predominant response resulting in serum
failure to thrive sickness
• Cow’s milk protein allergy characteristically • Antibody-mediated hemolysis by binding of
presents in breastfed infants with bloody stools, the drug to the surface of red blood cells
fussiness, and occasionally failure to thrive • Drug-induced, delayed-type hypersensitivity
reaction mediated by T-lymphocyte and
Diagnosis monocytes
• Skin testing
• ELISA Timing of reaction
• Oral food challenge (the gold standard) • If the drug given IV and an immediate reac-
• Food allergy may play a causative role in a tion occurs within an hour, an IgE-mediated
select group of children with severe atopic der- (type 1) process is likely
matitis; diagnosis in these cases may require the • If the reaction is delayed up to 72 h, a non-
implementation of an elimination diet with the IgE-mediated reaction is more likely
subsequent monitoring of skin manifestations • Steven–Johnson syndrome, toxic epidermal
necrolysis, fixed drug reactions, and photo-
Treatment sensitivity usually appear more than 72 h
• Avoidance is the mainstay of treatment after exposure to drugs
• Oral and epicutaneous immunotherapy are
novel therapeutic modalities in development Specific drug reaction
• Penicillin is composed of benzylpenicillin,
Prognosis which is the major determinant of penicillin
• Allergies to peanuts, tree nuts, fish, and shell- allergies
fish tend to be lifelong • Minor determinants, e.g., benzylpenicilloate,
• Most infants and children outgrow allergies are responsible for most anaphylaxis
to egg, milk, and soy protein
• Cow’s milk protein allergy usually resolves Cross-reactivity
in the second year of life • Penicillin cross-reacts with cephalosporin at
a rate of 3–7%
• Penicillin has a high rate of cross-reactivity
with imipenem
ADVERSE DRUG REACTIONS
• Penicillin has no cross-reactivity with aztreo-
nam, per current reporting
• Many drug reactions are idiosyncratic
(nonimmune) Desensitization
• Drug overdose • Desensitization is necessary if the medication
• Drug-drug interaction is the only clinically effective therapy
• Drug side effects • For example, a pregnant woman with syphi-
• Some drug reactions are triggered by an lis or a person with neurosyphilis requiring
immune response to the drug. All types of definitive penicillin therapy; both require
hypersensitivity (Table 11.1) have been impli- desensitization and use of IV penicillin
cated in these immune-mediated drug • Subsequent administration down the road
reactions may require repeat desensitization
• Lymphadenopathy
SERUM SICKNESS • Neurologic manifestation, e.g., peripheral
neuropathy
• Serum sickness is a type III hypersensitivity • Stop the offending agent
reaction that results from the injection of • NSAIDs can help for fever and muscle/bone
heterologous or foreign protein or serum pain
• Immune complex causes vascular injury and • Diphenhydramine or hydroxyzine will help
influx of neutrophils and eventual tissue to relieve urticaria and itching
injury or death • Prednisone 1–2 mg/kg/day can be given if
• Reactions secondary to the administration of other interventions are not helpful
nonprotein drugs are clinically similar to
serum sickness reactions
• Serum sickness does not require prior expo- ALLERGIC REACTIONS
sure to an antigen (prior sensitization) and
can occur on initial exposure
TO INSECTS
• The most common cause of serum sickness
today is antibiotics, e.g., cefaclor and • Insect stings usually result in site-limited
penicillin transient pain, itching, and swelling
• Stings from Hymenoptera (bees, wasps, and • Allergic reactions of varying severity can
some ants) can induce serum sickness occur in previously sensitized patients and
can be life-threatening
Clinical presentation • Recurrent systemic reactions to venom tend
• It may take 6–12 days for the reaction to to be similar in severity to the initial reaction
develop, but can take up to 3 weeks in an individual patient
• If previous exposure has occurred, a reaction
may occur as quickly as 1–3 days post-exposure Clinical presentation
• Fever/malaise • There are three common types of allergic
• Skin rash: Urticarial (92%) and/or serpigi- reactions to the venom of Hymenoptera
nous, the rash typically starts on the anterior (includes bees, yellow jackets, wasps, hor-
lower trunk or the periumbilical or axillary nets, and fire ants):
regions and spreads to the back, upper trunk, 1. Anaphylactic reactions (i.e., involving
and extremities multiple organ systems)
• Arthritis is usually in the metacarpophalan- 2. Systemic cutaneous reactions (wide-
geal and knee joints and usually symmetrical spread) include widespread pruritus,
• Edema may occur, particularly the face and hives, erythema, and/or angioedema
neck developing shortly after the sting. Can be
• Renal manifestations include proteinuria, dangerous if they involve edema of the
microscopic hematuria, and oliguria lips, tongue, or structures near the airway.
• GI complaints They may take several days to resolve
• Headaches fully
• Myalgias 3. Large local reactions (contiguous to
• Blurred vision the site) usually result in delayed and
• Dyspnea/wheezing prolonged local inflammation that
increases over 24–48 h. Take 3–4 days to –– Considered in selected patients with a his-
resolve tory of moderate-to-severe cutaneous sys-
temic reaction
Diagnosis –– Offered to very selected patients with a his-
• History of insect sting and symptoms consis- tory of repeated large local reactions
tent with an allergic reaction
• Presence of positive skin test and/or ele-
vated serum levels of venom-specific
immunoglobulin SKIN TESTING
• Testing can be done as soon as 1 week fol-
lowing the sting, but if negative and the his-
tory is convincing, it should be repeated Background
5–6 weeks later (transient anergy) • Skin prick tests are the most common screen-
ing tests for patients suspected to have aller-
Management gies. Both environmental and food allergies
• Anaphylactic reactions can be tested this way
–– Epinephrine • Skin testing is highly sensitive and safe even
–– Other medications as per standard manage- in very young children
ment of anaphylaxis • These tests provide useful and reproducible
–– Prescribe epinephrine autoinjector clinical information in a short period (i.e.,
–– Refer to an allergist for venom 15–20 min), with minimal expense and negli-
immunotherapy gible risk to the patient
• Systemic cutaneous reactions
–– Antihistamines Indications
–– Consider corticosteroids • Identification of aeroallergen triggers in
–– Consider prescribing an epinephrine auto- patients who have asthma
injector to patients with a history of mod- • AR not controlled with usual medications,
erate-to-severe systemic cutaneous specific avoidance is desired in such cases,
reactions e.g., pet dander
–– Consider referral to an allergist for venom • Food allergy
immunotherapy • Insect sting allergy
• Large local reactions • Vaccine, drug, or latex allergy
–– Ice pack • Evaluation for moderate-to-severe atopic
–– NSAIDs dermatitis
–– Antihistamines • Other conditions, including allergic fungal
–– Consider corticosteroids sinusitis, allergic bronchopulmonary asper-
• Venom immunotherapy gillosis, and eosinophilic esophagitis
–– Effective in reducing the severity of aller-
Medication that alters the result of skin test
gic reactions
• First-generation nonselective antihistamines,
–– Minimum 5-year duration
e.g., diphenhydramine, suppress skin reactiv-
–– Indicated in all patients with a history of
ity for 3 days
anaphylactic reaction to an insect sting and
• Second-generation antihistamines (e.g., ceti-
positive venom skin test or elevated serum
rizine, loratadine) may blunt skin test for up
levels of venom-specific IgE
to 7 days
• Ranitidine and famotidine may blunt the skin ity to a particular allergen. In contrast, a
test for up to 7 days negative skin-prick test is strong evidence
• Tricyclic antidepressants and phenothiazines against clinically relevant allergy to the tested
may block skin reactivity for 2 weeks allergen
Medications do not interfere with allergy skin

test eneral Rules in the Management
G
• Corticosteroids of Allergies
• Asthma medications, e.g., albuterol and
montelukast Avoidance of specific triggers
• Exposure to indoor allergens can be mini-
Method of testing mized with relatively simple measures
• A small amount of concentrated allergen is • Outdoor allergens are usually more difficult
deposited on the skin and a tiny puncture is to avoid
made with a plastic device • Strict avoidance of food allergens, including
• IgE receptors undergo cross-linking and acti- hidden sources and restaurant meals
vate mast cells, causing a release of histamine • Selection of alternative medications in the
and other products leading to local vasodila- case of drug allergies
tation and increased vascular permeability, • Latex-free materials during procedures for
resulting in wheals patients with latex allergies
Medications
In Vitro Allergy Testing • First-generation antihistamine: Diphenhydr-
amine, chlorpheniramine, and hydroxyzine
Enzyme-linked immunosorbent assay (ELISA) –– Adverse effects of first-generation
• Radioallergosorbent (RAST) testing is out- antihistamines:
dated because of radiation and is rarely used ◦◦ Sedation
today ◦◦ Interaction with acetylcholine receptors
• ELISA, which uses antibodies linked to and can cause dry mouth, blurry vision
enzymes, as well as fluorescent enzyme • Second-generation antihistamine: Cetirizine,
immunoassay (EIA) and chemiluminescent fexofenadine, loratadine, and desloratadine
immunoassays –– Does not cross the blood–brain barrier and
• The accuracy of immunoassays varies with are more specifically aimed at H1 receptor
the system being used and the quality of the and not the other receptors
allergen • Steroid
• There is a good predictive value (> 90%) for –– Intranasal corticosteroids are the most effec-
pollens of grass, trees, dust mites, and cats, tive agents for nasal allergy and do not have
whereas less accurate results may be the systemic effects seen with oral steroids
obtained from venoms, weeds, latex, dogs, –– Inhaled corticosteroids are important treat-
and molds ment measure in the patient with persistent
• If testing is equivocal, it can be further evalu- asthma
ated by skin testing and, if indicated, a chal-
lenge to the allergen Immunotherapy
• Both skin and ELISA are evidence of sensiti- • Only therapy capable of changing the course
zation but not necessarily of clinical reactiv- of allergic disease
• The goal is to decrease the severity of reac- –– Humoral immunity (antibodies)

tion upon exposure –– Cell-mediated immunity
• Permanent cure (tolerance) can be achieved –– Memory response
in some cases
–– Involves giving increasing doses of aller-
gens via the subcutaneous, sublingual, or T -Lymphocytes
oral route to induce an alteration in the
Characteristics
immune response to the allergen
• T-cells mature in the thymus
–– Usually takes 1–2 years before beneficial
• Play a central role in cell-mediated immunity
effect occurs. Minimum length of therapy
• Cell surface marker: CD3+
estimated around 5 years
–– Effective in the treatment of venom allergy, Subtypes of T-lymphocytes
pollen allergies, dust mites, and animal • Helper T-cells (CD4+ T-cells)
dander allergies –– Promote maturation of B-cells and interact
–– Efficacy currently being tested for the with B-cells to allow antibody production
treatment of IgE-mediated food allergies –– Interact with cells that express class II
–– Local reactions are common, but systemic major histocompatibility complex (MHC),
(anaphylactic) reactions can occur during which is loaded with extracellular proteins
allergen immunotherapy • Cytotoxic T-cells (CD8+ T-cells)
–– Kill cells infected by intracellular bacteria/
virus/cancer
–– Recognize their targets by binding to an
IMMUNOLOGY
antigen associated with MHC class I mol-
ecules, which are present on the surface of
Overview of the Immune System
all nucleated cells
Two main arms of vertebrate immunity
• Innate immune system (rapid and always
-Cells
B
available)
–– Physical barriers—skin, hair, cilia, mucous Background
membranes, mucous and chemical secre- • B-cells mature in the bone marrow
tions, digestive enzymes, stomach acid, etc. • B-cells are surface membrane immunoglobulin-
–– Internal defenses—inflammatory positive. B-cell receptor composed of
responses, complement proteins, phago- membrane-bound IgG, IgA, IgM, IgE, or IgD
cytic cells, natural killer (NK) cells • Cell surface marker: CD19+/CD20+
–– NK cells: Do not require antigen to be pre-
sented with HLA antigen Antibodies (IgG, IgA, IgM, IgE, and IgD)
◦◦ Produce large quantities of interferon- • IgG: In its four forms (IgG1, IgG2, IgG3,
gamma, IL-4, and granulocyte-macrophage and IgG4) provides the majority of antibody-
colony-stimulating factor, and multiple based immunity against invading pathogens.
other cytokines and chemokines (IL-2, The only antibody capable of crossing the
IL-13, IL-17, IL-21, and TNF-alpha) placenta to give passive immunity to the
• Adaptive immune system (recognizes “self” fetus
versus “non-self,” tailors immune response • IgM: Expressed on the surface of B-cells
for specific pathogens/infected cells, pos- (monomer) and in a secreted form (pentamer)
sesses immunologic memory) with very high avidity. Eliminates pathogens
in the early stages of disease before class • Normal ESR makes chronic bacterial and
switching to other immunoglobulin isotypes. fungal infection unlikely
Good at activating complement
• IgA: Main immunoglobulin in mucosal Additional testing for B-cell defects
secretions. Found in mucosal areas such as • Quantitative immunoglobulins (IgG, IgA,
the gut, respiratory tract, and urogenital and IgM)
tract and prevents colonization by patho- • Antibody titers to vaccines (e.g., tetanus,
gens. Also found in saliva, tears, and breast diphtheria, Haemophilus influenzae type B,
milk and pneumococcus)
• IgD: Functions mainly as an antigen receptor • Isohemagglutinins
on B-cells that have not been exposed to anti-
gen. Has been shown to activate basophils and Additional testing for T-cell defects
mast cells to produce antimicrobial factors • T-cell quantification
• IgE: Binds to allergens and triggers histamine • T-cell functional studies: Lymphocyte prolif-
release from mast cells and basophils and is eration assay to mitogens (phytohemaggluti-
involved in allergy. Also protects against nin, concanavalin A, pokeweed mitogen) and/
parasites or to antigens (candida, tetanus)
• T-cell receptor excision circles (TREC); new-
born screening (as of December 2018, all
Initial Immunologic Testing newborns in the United States are screened for
of a Child with Recurrent Infections severe combined immunodeficiency (SCID))
CBC with manual differential and erythrocyte Additional testing for phagocyte defects
sedimentation rate (ESR) • Absolute neutrophil count
• Normal absolute lymphocyte count rules • Neutrophil oxidative burst assay (dihydrorho-
against T-cell defect damine [DHR] assay)
• Normal absolute neutrophil count rules
against congenital or acquired neutropenia Additional testing for complement deficiencies
• Normal platelet count excludes Wiskott– • CH50
Aldrich syndrome
• Absence of Howell–Jolly bodies rules against Clinical patterns in some of the primary immu-
asplenia nodeficiencies (Table 11.2)
Table 11.2 Clinical patterns in some of the primary immunodeficiencies

Clinical features Diagnosis
0–6 months of age
Unusual facial features, hypocalcemia, heart disease (conotruncal) 22q11.2 deletion syndrome (DiGeorge syndrome)
Delayed umbilical cord detachment, leukocytosis, recurrent Leukocyte adhesion defect
infection
Persistent thrush, pneumonia, failure to thrive, diarrhea, small Severe combined immunodeficiency
tonsils, nonpalpable lymph nodes, profound lymphopenia, usually
present in the first few months of life
Bloody stools, draining ears, small platelets, atopic eczema Wiskott–Aldrich syndrome
4- to 9-month-old with recurrent mild infections, but appropriately Transient hypogammaglobulinemia
makes antibodies to diphtheria and tetanus toxoids of infancy (THI)
6 months to 5 years
Boy presents between 6 and 9 months with severe and recurrent X-linked agammaglobulinemia
infection, absent antibodies and absent tonsils
(continued)
Clinical features Diagnosis
Severe progressive infectious mononucleosis X-linked lymphoproliferative syndrome
Recurrent staphylococcal abscesses, staphylococcal pneumonia Hyper-IgE syndrome
with pneumatocele formation, coarse facial features, pruritic
dermatitis
Persistent thrush, nail dystrophy, endocrinopathies Chronic mucocutaneous candidiasis
Short stature, fine hair, severe varicella Cartilage–hair hypoplasia with short-limbed
dwarfism
Oculocutaneous albinism, recurrent infections, silvery hair Chediak–Higashi syndrome
Boy with liver abscesses, suppurative lymphadenopathy, antral Chronic granulomatous disease
outlet obstruction, pneumonia, osteomyelitis, nitroblue
tetrazolium (NBT) or dihydrorhodamine assay reduced or no
color change
Recurrent respiratory, gastrointestinal, and genitourinary tract IgA deficiency
infections, many patients are asymptomatic, risk of anaphylaxis
with blood products
Older than 5 and adults
Healthy male until acquires fulminant often fatal infectious X-linked lymphoproliferative syndrome
mononucleosis or EBV infection (mean age of presentation is
< 5 years)
Sinopulmonary infections, neurologic deterioration, telangiectasia Ataxia–telangiectasia
Recurrent Neisseria infections Terminal complement defect
Sinopulmonary infections, normal B-cell counts, Common variable immunodeficiency
hypogammaglobulinemia, autoimmune cytopenias
EBV Epstein–Barr virus
DISORDERS OF PHAGOCYTE –– Burkholderia (Pseudomonas) cepacia

–– Serratia marcescens
FUNCTION –– Nocardia spp.
–– Outside of the United States: Salmonella
hronic Granulomatous Disease
C
and bacillus Calmette–Guérin (BCG)
(CGD) • Most common sites of disease: Lung, skin,
lymph nodes, GI, liver, urinary tract
Background • Autoimmune/inflammatory complications
• Defect in NADPH oxidase complex
• Neutrophils unable to generate hydrogen per- Diagnosis
oxide or hydroxyl radicals (superoxides) to • DHR assay: Functional neutrophils take
kill phagocytosed organisms up DHR and oxidize it to a green fluores-
• X-linked form most common; AR disease cent compound detectable by flow
also occurs cytometry
• Nitroblue tetrazolium (NBT): An older
method that is now less used due to operator
• Pyogenic infections of the skin, lungs, bones,
subjectivity and higher false-negative rate
liver, and GI tract
–– Normal: NBT oxidized to purple/blue
• Characteristic infections with
color
–– Aspergillus spp.
–– CGD: Reduced or no color change
–– Staphylococcus aureus
Treatment • Mutation in CHS1/LYST gene on chromo-

• Prophylactic antibiotics (antibacterial and some 1q42.1-2
antifungal) • Disease characterized by abnormal lyso-
• Interferon (IFN)-gamma can be added somes/granules in all cell types
• Aggressive treatment of infections
• Definitive therapy: Clinical presentation
–– Hematopoietic cell transplant • Partial oculocutaneous albinism due to
–– Gene therapy improper transfer of melanosomes to epithe-
lial cells (fair skin, light blond/gray/white
hair)
Leukocyte Adhesion Defect • Neutrophil abnormalities (impaired chemo-
taxis and dysfunction)
Background –– Contains giant azurophilic granules that do
• Defect in adhesion molecules that allow neu- not release contents with infection
trophils to leave circulation in response to –– Recurrent pyogenic infections (mostly skin
infection and respiratory tract)
• Keywords: Delayed umbilical cord separa- • Coagulation defects due to decreased platelet
tion, leukocytosis stores
• Progressive neurologic abnormalities
Clinical presentation • “Accelerated phase”—massive systemic
• Delayed umbilical cord separation > 1 month lymphohistiocytosis
• Leukocytosis with average white blood cell
(WBC) count (45 × 109/L) Risk of malignancy
• Recurrent bacterial infections, especially staph- • Life-threatening lymphoma-like syndrome
ylococcal infections (recurrent skin abscess) • Leukemia and lymphoma
• Absence of pus and neutrophils at the wound • Lymphohistiocytic infiltration of the liver,
site spleen, and lymph nodes
• Poor wound healing • Pancytopenia
• Fulminant Epstein–Barr virus (EBV) infections
Diagnosis
• Delayed separation of an umbilical cord and Diagnosis
persistent high WBC count is highly suggestive • Classic giant azurophilic granules (peroxi-
• Flow cytometric measurements of surface dase positive) in neutrophils, eosinophils, and
glycoprotein (CD18 or CD11) expression granulocytes
• Neutropenia
Treatment • Poor NK-cell cytotoxicity
• Prophylactic antibiotics • B-cell function usually normal
• Definitive therapy with hematopoietic cell
transplant Treatment
• Prophylactic antibiotics/aggressive treatment
of infections
Chediak–Higashi Syndrome • Hematopoietic cell transplantation (but does
not correct neurologic decline or oculocuta-
Background neous albinism)
ANTIBODY DEFICIENCY X-Linked Agammaglobulinemia

SYNDROMES Background
• Defect in Bruton tyrosine kinase (BTK) caus-
Transient Hypogammaglobulinemia
ing arrest in B-lymphocyte development
of Infancy (THI) • Almost no circulating B-cells →
panhypogammaglobulinemia
Background
• Maternal IgG traverses placenta to the Clinical presentation
fetus throughout gestation; most pro- • Presents at 3–9 months of age when mater-
nounced during the latter half of the third nally transferred antibodies disappear
trimester • Unusually severe or recurrent bacterial respi-
• After birth, IgG levels in the infant fall as ratory tract infections
newborn IgG contribution is still catching up, –– Sequelae of infections include chronic
resulting in a physiologic IgG nadir cough, rhinitis, digital clubbing, and fail-
• THI results from a prolongation of the physi- ure to thrive
ologic hypogammaglobulinemia that usually • Absence or near absence of B-cell-rich ton-
occurs around age 3–6 months sils and adenoids
• Most common age of developing symptoms • Episodes of sepsis with encapsulated
is 6–12 months bacteria
• Increased susceptibility to certain infections
such as enterovirus (echovirus, coxsackie),
• Most infants are asymptomatic, but some can
causing meningoencephalitis or hepatitis,
develop recurrent respiratory infections (oti-
even with adequate IgG replacement
tis media and bronchial infections)
• Life-threatening infections (cellulitis, bacte- Diagnosis
remia, meningitis) are unusual but may • Absent circulating CD19+/CD20+ B-cells by
occur flow cytometry
• T-cell immunity is intact • Very low serum IgG, IgA, IgM
• By definition, a self-limited disorder • Deficient antibody responses to
–– Recurrent infections usually resolve by immunizations
9–15 months of age • Neutropenia in ~20% of patients
–– IgG normalizes by 2–4 years of age (but • Absent BTK expression by flow cytometry
can take up to 10 years) • Abnormal BTK gene sequencing
Diagnosis Treatment
• Low serum IgG levels • IgG replacement
• Antibody titers to protein immunizations • Aggressive treatment of infections
(e.g., tetanus toxoid, diphtheria toxoid, polio)
are at normal or near-normal concentrations
Common Variable Immune
Treatment
• Supportive
Deficiency (CVID)
• Antibiotic prophylaxis Background
• IgG replacement can be considered in severe • Markedly reduced serum IgG in combination
cases with low IgA and/or IgM
–– Poor or absent response to immunizations S elective IgA Deficiency (sIgAD)

–– Absence of other defined
immunodeficiencies Background
• Genetics: Most cases are sporadic and likely • sIgAD is the most common immunologic
due to multiple genes, but more monogenic defect in humans
causes are being identified • Deficiency of serum IgA in the setting of nor-
• Usually in the second and third decades and mal IgG and IgM in an individual > 4 years of
very rare before the age of 6 years age

• Recurrent infections—Permanent damage to • Majority are asymptomatic
the bronchi may occur, resulting in • Various GI tract infections with viruses and
bronchiectasis bacteria
• As many as 20% of patients with CVID • Giardia manifests as chronic diarrhea with or
develop autoimmune complications: without malabsorption
–– Immune thrombocytopenia (ITP) • Recurrent sinopulmonary infections can occur
–– Autoimmune hemolytic anemia (AIHA) • Increased incidence of autoimmunity and
–– Evans syndrome atopy
–– Rheumatoid arthritis
–– Systemic lupus erythematosus (SLE) Diagnosis
–– Autoimmune thyroid disease • Very low or absent IgA
• GI diseases also commonly associated (mal- • Low serum IgA levels in children aged
absorption, chronic diarrhea, inflammatory 6 months to 4 years should be confirmed to be
bowel disease) persistently low at age 4 years before making
a lifetime diagnosis of sIgAD
Risk of malignancy
• Increased risk of malignancy, particularly Treatment
non-Hodgkin lymphomas • Antibiotics
• Clean drinking water due to increased risk of
Diagnosis Giardia
• Quantitative immunoglobulins (IgG, IgA,
IgM)
• Evaluation of antibody responses after immu-
DEFECTS OF CELLULAR
nization with polysaccharide and protein con-
jugate antigens IMMUNITY
Treatment
• IgG replacement 22q11.2 Microdeletion Syndrome/DiGeorge
• Antibiotics for bacterial infections Syndrome (see Table 11.2)
• Treatment of autoimmunity. (Note: autoim-
munity needs to be diagnosed clinically, since Background
patients may not have detectable autoanti- • Microdeletion at 22q11.2 → disorder of third
body production) and fourth pharyngeal pouches
• Monitoring for malignancy • CATCH 22
–– Cardiac (conotruncal: tetralogy of Fallot,
truncus arteriosus, interrupted aortic arch)
–– Abnormal facies (short philtrum, low-set Prognosis

ears, hypertelorism, antimongoloid slant) • Varies significantly—depends on the nature
–– Thymic hypoplasia and degree of involvement of different
–– Cleft palate (palate anomalies, speech organs
delay, learning disability) • Many live long productive lives
–– Hypoparathyroidism with hypocalcemia
and tetany
–– Chromosome 22 hronic Mucocutaneous Candidiasis
C
• Types (CMC)
–– Partial DiGeorge syndrome (most
common) Background
–– Complete DiGeorge syndrome (< 1% of • The unifying feature of these heterogeneous
cases); association with CHARGE disorders is impaired cell-mediated immunity
(Coloboma [eye]; Heart defects of any against Candida species
type; Atresia [choanal]; Retardation [of • Classic forms are due to mutations in the
growth and/or development]; Genital autoimmune regulator gene (AIRE) and sig-
anomaly; Ear anomaly) syndrome nal transducer and activator of transcription 1
gene (STAT1)
• Cardiac abnormalities (ranges from asymp- Clinical presentation
tomatic to cyanotic) • Endocrinopathies
• Neonatal hypocalcemia • Autoimmunity: AIHA, ITP, autoimmune
• Immunodeficiency: Ranges from asymptom- neutropenia
atic to recurrent sinopulmonary infections to • Immunodeficiency
severe combined immunodeficiency, depend- –– Abnormal T-cell proliferation to Candida
ing on the degree of thymic hypoplasia antigen
• Intellectual disability –– Increased bacterial and viral infections
Diagnosis Diagnosis
• Serum calcium and phosphorus • Evaluation for immunodeficiency (CBC,
• Lymphocyte count (SCID workup if there is quantitative immunoglobulins, vaccine anti-
evidence of complete DiGeorge syndrome) body titers, lymphocyte subsets, lymphocyte
• Chest radiograph to evaluate for thymic proliferation studies)
shadow • STAT1 function can be evaluated by flow
• Immunoglobulin levels +/− vaccine antibody cytometry
titers if indicated • The definitive test is a genetic analysis
• Renal ultrasound to rule out genitourinary • Endocrine evaluation
tract abnormalities
• Genetic analysis (FISH, now being replaced Treatment
by microarray) • Systemic antifungal therapy
• Treatment of associated endocrinopathies
Treatment for complete DiGeorge syndrome and autoimmunity
• Thymus transplant • IgG replacement if indicated
• Hematopoietic cell transplant
-Linked Lymphoproliferative (XLP)

X • Autosomal recessive (DOCK8) also occurs
Syndrome but more rare

• Mutation in signaling lymphocyte activation • AD HIES
molecule (SLAM)-associated protein (SAP) –– Recurrent skin abscesses
gene –– Eczema
–– Recurrent pneumonia with pneumatoceles
Clinical presentation (staphylococcal infections)
• Healthy male until EBV infection –– Mucocutaneous candidiasis
• Average of presentation is 2.5 years –– Coarse facial features
• Fulminant, often fatal infectious mononu- –– Bone fractures, scoliosis
cleosis causing multi-organ failure
–– Can result in secondary hemophagocytic Diagnosis
lymphohistiocytosis (HLH) • Elevated serum IgE levels (does not correlate
• Dysgammaglobulinemia with disease severity)
• Lymphoproliferative disease, predominantly • Eosinophilia
non-Hodgkin B-cell lymphomas • Some have decreased IgG levels and poor
• 70% of affected boys die by age 10 vaccine antibody responses
Diagnosis Treatment
• EBV studies • Skin care (hydration and control of itch)
• Peripheral blood smears will show atypical • Prophylactic antibiotics to prevent cutaneous
lymphocytosis, particularly CD8+ T cells and respiratory infections
• Hypogammaglobulinemia is common • Aggressive treatment of infections
• NK-cell activity often reduced • Monitor/treat skeletal abnormalities
• Chemistry profiles will show transaminitis and • Hematopoietic cell transplantation addresses
other findings of acute hepatitis/liver failure immunodeficiency but not somatic
• HLH labs if indicated, including bone mar- abnormalities
row biopsy
• Mutation analysis for the SAP gene mutation
COMBINED ANTIBODY
Treatment AND CELLULAR
• Rituximab to ablate B-cells IMMUNODEFICIENCY
• IgG replacement
• Definitive therapy—hematopoietic cell Severe Combined Immunodeficiency
transplantation
(SCID)
Background
Hyper-IgE Syndrome (HIES) • Caused by multiple mutations (X-linked, AR,
or sporadic) that affect T- and B-cell
Background
development
• Autosomal dominant (AD) (STAT3) is more
• CD3 T-cell count typically < 300/μL
common
• CD19/CD20 B-cells and CD16/56 NK-cells • Adenosine deaminase (ADA) enzyme

may or may not be present, depending on the replacement for ADA-deficient SCID
genetic defect • Definitive: Stem cell transplant, preferably
• Keywords: Lymphopenia, chronic diarrhea, before the onset of severe persistent opportu-
thrush, failure to thrive, absent thymus, severe nistic infections and with a matched sibling
recurrent infections, bone abnormalities donor
–– Gene therapy available for some forms of
Clinical presentation SCID (ADA, X-linked, Artemis)
• Sibling death in infancy (e.g., multiple deaths –– Good survival with early transplant
during infancy due to infection or unex-
plained deaths) or previous miscarriages in Complications
the mother • Early graft-versus-host disease (GVHD) from
• Family history of SCID or other primary maternal cells crossing the placenta (maternal
immunodeficiency engraftment)
• Family history of consanguinity • Without intervention, SCID usually results in
• Most patients present before 3 months of age severe infection and death in children by
• Poor feeding 2 years of age
• Chronic diarrhea
• Recurrent infections, especially pneumonia
Wiskott–Aldrich Syndrome
• Very small/absent thymus
Background
Diagnosis
• Genetics: X-linked recessive (Xp11.22–23)
• Low CD3 T-cell count, usually < 300/μL.
• Results from mutations in Wiskott–Aldrich
(Note that the normal lymphocyte count in a
syndrome protein (WASp) (important in
newborn is ~2500/μL)
actin cytoskeleton remodeling and impacts
• Flow cytometry for lymphocyte subsets to
interactions between T-cells and APCs,
quantify CD3/4/8 T-cells, CD19 B-cells, and
B-cells, etc.)
CD16/56 NK-cells
• Keywords: Eczema, small platelet, bleeding,
• Abnormal lymphocyte proliferation studies
recurrent infection
to mitogens
• Low quantitative immunoglobulins (initially Clinical presentation
normal due to maternal transfer of IgG) • Classic triad
• No antibody response to vaccination –– Thrombocytopenia (small platelets)
• Newborn screening for T-cell receptor exci- –– Increased susceptibility to infections
sion circles (TREC) –– Eczema
• Prolonged bleeding from the umbilical stump
Treatment
or circumcision site
• Initial management: Protective isolation,
• Eczema is often seen during the first year of
intravenous immunoglobulin (IVIG),
life
Pneumocystis jiroveci pneumonia (PJP) pro-
• Recurrent infections (sinopulmonary infec-
phylaxis, fungal prophylaxis, no live vac-
tions, meningitis, and sepsis) with encapsulated
cines, palivizumab, cytomegalovirus (CMV)
bacteria including Streptococcus pneumoniae,
negative blood products, discontinue breast-
Neisseria meningitidis, H. influenzae
feeding if mother is CMV positive
• Hepatosplenomegaly –– Often appears healthy during the first year

• Autoimmunity: Cytopenias, vasculitis and begins to walk, but with slow
• Increased risk of lymphoma associated with progression
EBV infection and increased risk of –– Usually reliant on a wheelchair by 10 years
leukemia of age. Also, develop dysarthria around
• Bleeding is the main cause of death this time
• Telangiectasia
Diagnosis –– Conjunctiva (3–5 years of age)
• Early onset thrombocytopenia with small –– Cutaneous (on exposed areas such as pin-
platelets nae, nose, face, neck)
• Screening for WASp by flow cytometry • Immunodeficiency
• Gene sequencing –– Humoral and cellular immunodeficiency
• Other lab findings: –– Recurrent sinopulmonary infections
–– T-cell lymphopenia –– Infections outside of the respiratory tract
–– Abnormal lymphocyte proliferation are not increased
–– Abnormal immunoglobulin isotypes
–– Poor vaccine response Risk of malignancy
• Lymphoma and leukemia most common
Treatment • AT cells are susceptible to ionizing radiation
• Supportive care and chemotherapeutic drugs due to defective
–– IgG replacement DNA repair making treatment more difficult
–– Prophylactic antibiotics and late complications more common
–– Platelet transfusions
–– Skin care Diagnosis
–– Splenectomy to increase circulating plate- • Elevated alpha-fetoprotein level (AFP) in
lets. Not routinely recommended given children > 8 months of age
the increased risk of septicemia with –– Level does not correlate with disease
asplenia severity
• Definitive care • Wide range of immune laboratory
–– Hematopoietic cell transplantation abnormalities
–– Gene therapy –– Immunoglobulin deficiency (often IgA
and/or IgG subclasses)
–– Poor antibody response to polysaccharide
Ataxia-Telangiectasia vaccines
–– Lymphopenia, predominantly of T-cells
Background • Brain imaging: Cerebral atrophy and ventric-
• Affected gene: Ataxia–telangiectasia mutated ular enlargement
(ATM) at 11q22.3
• ATM is expressed in all tissues in the body. Treatment
Involved in DNA repair and recombination • IgG replacement
• Antibiotics
Clinical presentation • Close monitoring of chronic lung disease
• Progressive ataxia • Swallow evaluation
–– Usual presenting symptom
• Physical and occupational therapy Treatment

• Minimize tests with ionizing radiation • Immunoglobulin replacement
• Close monitoring for malignancy • Prompt treatment of infections
• Prevention of Cryptosporidium infection by
using boiled or filtered water
X-Linked Hyper-IgM Syndrome • Patients with neutropenia may benefit from
(XHIM) treatment with granulocyte colony-stimulat-
ing factor (G-CSF)
Background • Definitive: Hematopoietic cell
• Rare primary immunodeficiency caused by transplantation
mutations in CD40 ligand (CD40L)
–– CD40L (on T-cells) interacts with CD40
(on B-cells) to induce class switching of
IgM to other immunoglobulin isotypes
DISORDERS
• Considered a combined immune deficiency OF THE COMPLEMENT SYSTEM
because dendritic cells and monocytes/mac-
rophages also express CD40 and require Complement Defect
CD40L stimulation
Background
Clinical presentation • Initial defect: Associated with autoimmune
• Recurrent sinopulmonary infections (primar- diseases
ily encapsulated bacteria) • Terminal defect: Increased risk of infection
• Opportunistic infection (PJP pneumonia) is
often the presenting symptom
• Genetic deficiency of C1q, C1r/s, C2, C4, and
• Cryptosporidium infection is common and
C3 is associated with autoimmune inflamma-
causes biliary tract disease
tory diseases (SLE) and recurrent pyogenic
–– Common cause of chronic diarrhea that is
bacterial infections
present in a large percentage of patients
• Genetic deficiency of C5, C6, C7, C8, and C9
• Increased risk of malignancy
is associated with increased susceptibility to
Laboratory findings Neisseria infections (also some association
• Normal or elevated serum IgM levels associ- with rheumatic diseases)
ated with low or absent IgG, IgA, and IgE
Diagnosis
serum levels
• Complement (CH50) test: Screen for defi-
• Lack of antibody response to vaccines
ciencies in complement by performing the
• Approximately two-thirds of patients have
total serum classic hemolytic complement
neutropenia
(CH50) test
Diagnosis –– Note that complement hemolytic activity is
• Lack of CD40L expression on T-cells by flow unstable and temperature sensitive →
cytometry CH50 can be reduced if left only a few
• Absent CD40L function as measured by bind- hours at room temperature
ing to CD40 by flow cytometry • Direct measurement of individual serum
• Confirmatory gene sequencing complement proteins, such as C3 and C4, can
also be performed and is helpful in determin- • Normal T-lymphocyte counts in a newborn

ing the diagnosis are usually around 2500/μL. In SCID, CD3
T-cell counts are usually < 300/μL and must
Treatment be accompanied by poor T-cell function via
• Watch closely for meningococcal disease and lymphocyte proliferation assays.
treat early • Newborn screening for SCID is now per-
• Vaccination (especially meningococcal and formed in every state in the United States.
pneumococcal vaccines) • Terminal complement defects are associated
• Antibiotic prophylaxis is not routinely done, with recurrent Neisseria infections, while
but may be needed in some early complement defects are associated with
• Plasma infusions (to replace complement fac- autoimmunity.
tors) done very rarely • Hematopoietic stem cell transplant has the
potential to cure many immunodeficiencies
by using healthy donor stem cells that are
PEARLS AND PITFALLS capable of producing functional blood
immune cells. However, this will not address
somatic features of diseases such as ataxia
• Environmental allergies are responsible for a
telangiectasia, Chediak–Higashi syndrome,
large proportion of asthma exacerbations in
etc.
children 5 years and older.
• A positive skin test or an elevated IgE to a
particular allergen does not always translate
into clinical reactivity. Suggested Reading
• Atopic dermatitis developing the first few
months of life is an important risk factor for Arunachalam M, Sanzo M, Lotti T, Colucci R,
food allergies. Berti S, Moretti S. Common variable immuno-
• Allergen immunotherapy has been proven to deficiency in vitiligo. G Ital Dermatol Venereol.
be effective for treating environmental and 2010;145(6):783–8.
insect venom allergy. A similar approach is Bonilla FA, Khan DA, Ballas ZK, Chinen J, Joint
now being evaluated for the treatment of food Task Force on Practice Parameters, representing
allergies. the American Academy of Allergy, Asthma &
• Mastocytosis in children is usually limited to Immunology; the American College of Allergy,
the skin and follows a benign course. Asthma & Immunology; and the Joint Council
• Functional neutrophil disorders include the of Allergy, Asthma & Immunology, et al.
inability to generate superoxides to kill Practice parameter for the diagnosis and man-
phagocytosed organisms (CGD) or the inabil- agement of primary immunodeficiency. Ann
ity to properly adhere to blood vessels and Allergy Asthma Immunol. 2015;136(5):1186–
leave the circulation to sites of infection 1205.e78. https://www.jacionline.org/article/
(LAD). S0091-6749(15)00883-0/pdf. Accessed 4 Feb
• Most of a newborn’s IgG is received through 2019.
the placenta from the mother during the last Lieberman P, Nicklas RA, Oppenheimer J, Kemp
trimester. There is a physiologic nadir that SF, Lang DM, Bernstein DI, et al. The diagno-
occurs around 3–6 months of age. sis and management of anaphylaxis practice
parameter: 2010 update. J Allergy Clin Immunol. Scadding G. Optimal management of nasal con-
2010;126(3):477–80.e1-42. gestion caused by allergic rhinitis in children.
Munir AK, Björkstén B, Einarsson R, Ekstrand- Pediatr Drugs. 2008;10(3):151–62.
Tobin A, Möller C, Warner A, Kjellman Shprintzen RJ, Goldberg RB, Lewin ML, Sidoti
NI. Mite allergens in relation to home con- EJ, Berkman MD, Argamaso RV, et al. A new
ditions and sensitization of asthmatic chil- syndrome involving cleft palate, cardiac anom-
dren from three climatic regions. Allergy. alies, typical facies, and learning disabilities:
1995;50(1):55–64. velo-cardiofacial syndrome. Cleft Palate J.
National Asthma Education and Prevention 1978;15(1):56–62.
Program. Expert panel report 3: guidelines Tiller TL, Buckley RH. Transient hypogamma-
for the diagnosis and management of asthma, globulinemia of infancy: review of the litera-
Full Report 2007. NIH Publication 07-4051. ture, clinical and immunologic features of 11
Bethesda: National Heart, Lung, and Blood new cases, and long-term follow-up. J Pediatr.
Institute; 2007. 1978;92(3):347–53.
Endocrinology
12
Amr Morsi
GROWTH DISORDERS • Height and pubertal onset in parents can be

helpful in assessing the likelihood that simi-
Normal Growth Rate lar growth pattern in the child represents a
normal variation
• Birth length increases by 5% at 1 year
(approximately 25 cm or 10 in./year) Midparental target height (MPTH)
• At 1–2 years of age, children grow 12.5 cm or • Calculated as an average ± 2 SD (1 SD = 2 in.)
5 in./year (approximately half the growth rate
Midparental height (MPH) for boys
of the 1st year of life)
• Paternal height + (maternal height + 13 cm or
• By 2 years of age, children are approximately
5 in.)/2
half of their final adult height
• After 2–3 years of age, height increases by MPH height for girls
approximately 6.25 cm or 2.5 in./year • Maternal height + (paternal height −13 cm or
• Careful attention to growth rate (not only the 5 in.)/2
height) facilitates early detection of a growth-
slowing disorder
Short Stature
What is the relationship between the linear
growth rate and weight gain? Classification
• Poor nutrition and excess caloric intake can Normal variant short stature
influence linear growth • Constitutional delay of growth and puberty
• If a weight deceleration precedes and is (CDGP)
greater than the height deficit, the child needs • Familial short stature
a gastrointestinal consultation (Fig. 12.1) • Idiopathic short stature
• Excess weight gain associated with a decline
in growth rate is not nutritional and requires Pathological short stature
endocrine consultation • Chronic disease
• Chronic undernutrition
Family history of pubertal onset, age of adult • Endocrine disorders (e.g., growth hormone
height attainment, and bone age deficiency [GHD], hypothyroidism, Cushing
syndrome)
A. Morsi (*)
• Genetic syndromes (e.g., Turner, Noonan)
Division of Endocrinology, Department of Pediatrics, UPMC • Psychosocial
Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
e-mail: amr.morsi@chp.edu

418 A. Morsi
Fig. 12.1 Growth curve of a 2 to 20 years: Boys NAME

child with failure to thrive Stature-for-age and Weight-for-age percentiles RECORD #
secondary to malabsorption.
12 13 14 15 16 17 18 19 20
Weight is affected before height
Mother’s Stature Father’s Stature cm in
(http://www.cdc.gov/ Date Age Weight Stature BMI* AGE (YEARS) 76
growthcharts) S
190
95 74 T
90
185 A
72 T
75
180 U
50 70
175 R
25 68 E
*To Calculate BMI: Weight (kg): Stature (cm): Stature (cm) × 10,000
or Weight (lb) + Stature (in) + Stature (in) × 703
10
170 MPH
66
in cm 3 4 5 6 7 8 9 10 11 5 165
64
160 160
62 62
S 155 155
60 60
T 150 150
A 58
T 145
U 56
140 105 230
R 54
E 135 100 220
52
130 95 95 210
50
125 90 200
48 90
190
120 85
46 180
115 80
75
44 170
110 75
42 160
105 50 70
150 W
40
100 65 140 E
25
38 I
95 60 130
10 G
36 5
90 55 120 H
34 T
85 50 110
32 80 45 100
30 90
40
80 35 80
35
W 70 70
30 30
E 60 60
I 25 25
G 50 50
H 20 20
40 40
T 15 15
30 30
10 10
lb kg AGE (YEARS) kg lb
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Published May 30, 2000 (modified 11/21/00).
SOURCE: Developed by the National Center for Health Statistics in collaboration with
the National Center for Chronic Disease Prevention and Health promotion (2000).
http://www.odc.gov/growthcharts
linical Approach for Evaluating Short

C Physical examination
Stature and Poor Linear Growth • Anthropometric measurements to deter-
mine height and weight percentiles, as
History well as linear growth velocity and weight
• Birth history (intrauterine growth retardation gain
[IUGR], small for gestational age [SGA]), • Detailed physical examination to look for
developmental history, and history of chronic signs of genetic syndromes, endocrinopa-
illnesses thies, and signs of pubertal development
• Parental history of pubertal onset in males • Parental height for determining the mid-paren-
and menarche in females tal height (MPH) and MPTH height range
12 Endocrinology 419
Laboratory evaluation • Most children resume a normal growth veloc-

• Indications: Height ≤ 2 SD below the mean ity by the age of 2–3 years
for age, sex, and population or poor linear • During childhood, these individuals grow
growth (i.e., reduced growth velocity): along or parallel to the lower percentiles of
–– Complete blood count (CBC) the growth curve
–– Electrolytes • Children with CDGP are often referred to as
–– Calcium, phosphate, and alkaline phospha- “late bloomers” with onset of puberty also
tase (Ca, Phos, ALP) being later than peers
–– Celiac disease screen: Total immunoglobu-
lin A (IgA), tissue transglutaminase (tTG) Diagnosis
IgA • Family history of growth and pubertal delay
–– Thyroid-stimulating hormone (TSH,) free is common (in 50% of cases)
thyroxine 4 (free T4) • Delayed bone age
–– Erythrocyte sedimentation rate (ESR), • Linear growth is 2 SD deviation below the
C-reactive protein (CRP) mean for age in the first 3 years of life
–– Insulin-like growth factor 1 (IGF-1), IGF (Fig. 12.2)
binding protein 3 (IGFBP-3) • Pubertal growth spurt is delayed, and the
–– Bone age radiograph for skeletal growth rate continues to decline after those
maturation of their classmates have begun to
–– Karyotype (for girls) accelerate
• IGF-1 tends to be low for chronological age
Imaging: Bone age radiograph to determine but normal for bone age
skeletal maturation • GH and thyroid studies are usually normal
• Bone age will be similar to chronological age
in familial short stature and genetic causes of Management
short stature • Medical care in CDGP is aimed at obtaining
• Bone age will be more delayed than the chron- several careful growth measurements at fre-
ological age in CDGP and endocrinopathies quent intervals, often every 6 months
–– Bone age is usually mildly delayed in • These measurements are used to calculate
CDGP (usually > 2 SD below mean for age linear height velocities and to establish a tra-
and sex) jectory on the growth curve
–– The degree of bone age delay in endocri- • Medical treatment of this variation of normal
nopathy will depend on the duration of dis- growth is not necessary but may be initiated
ease, e.g., in severe long-standing GHD, in adolescents experiencing psychosocial
the bone age is usually > 3 SD below the distress
mean for age and sex • Boys with more than 2 years of pubertal delay
may benefit from a short course of testoster-
one therapy after the age of 14 years
onstitutional Delay of Growth
C
and Puberty (CDGP)
Familial Short Stature (FSS)
Background
• The most common cause of short stature and Background
pubertal delay • Height below the fifth percentile
• Typically have retarded linear growth within • Growth velocity, i.e., parallel to but below the
the first 3 years of life normal growth curve (Fig. 12.3)
420 A. Morsi
Fig. 12.2 Short stature 2 to 20 years: Boys NAME

secondary to constitutional delay. Stature-for-age and Weight-for-age percentiles RECORD #
Growth is noted along or parallel
12 13 14 15 16 17 18 19 20
to the lower percentiles of the
growth curve and pubertal AGE (YEARS) 76
Date Age Weight Stature BMI* S
initiation is also delayed. 190 T
95 74
Catch-up growth is noted from 90 A
185
age of 16 to 17 years, and at 72 T
75
19 years of age, the boy reached 180 U
70 R
his midpaternal target height 50
175 E
(“late bloomer”) (http://www. 25 68
170 MPH
cdc.gov/growthcharts) or Weight (lb) + Stature (in) + Stature (in) × 703
10 66
in cm 3 4 5 6 7 8 9 10 11 5 165
64
160 160
62 62
S 155 155
60 60
T 150 150
A 58
T 145
U 56
140 105 230
R 54
E 135 100 220
52
130 95 95 210
50
125 90 200
48 90
190
120 85
46 180
115 80
75
44 170
110 75
42 160
105 50 70
150 W
40
100 65 140 E
25
38 I
95 60 130
10 G
36 5
90 55 120 H
34 T
85 50 110
32 80 45 100
30 90
40
80 35 80
35
W 70 70
30 30
E 60 60
I 25 25
G 50 50
H 20 20
40 40
T 15 15
30 30
10 10
lb kg AGE (YEARS) kg lb
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Diagnosis • ISS is a diagnosis of exclusion. The diag-

• Bone age is congruent with child’s chrono- nosis is given after a comprehensive
logical age workup fails to identify cause for the short
• The time of pubertal onset is normal stature
• Height percentile tracks that predicted by • ISS is differentiated from normal variant
parental genetics short stature (CDGP, FSS) by a predicted
final adult height that is < –2 SD below the
child’s target height range
Idiopathic Short Stature (ISS) • GH therapy aiming to improve adult height is
• ISS is defined as a height ≤ 2 SD below the approved for ISS by the U.S. Food and Drug
mean for age, sex, and population Administration (FDA)
Fig. 12.3 Familial short 2 to 20 years: Boys NAME

stature. Growth rate is parallel Stature-for-age and Weight-for-age percentiles RECORD #
to the lower percentiles of the
12 13 14 15 16 17 18 19 20
growth curve and final adult
height corresponds to Date Age Weight Stature BMI* AGE (YEARS) 76
midpaternal target height 95
190
(http://www.cdc.gov/ 74
90
185 S
growthcharts) 75
72 T
180 A
50 70
175 T
25 68 U
170 R
10 66
165 E
in cm 3 4 5 6 7 8 9 10 11 5
64 MPH
160 160
62 62
S 155 155
60 60
T 150 150
A 58
T 145
U 56
140 105 230
R 54
E 135 100 220
52
130 95 95 210
50
125 90 200
48 90
190
120 85
46 180
115 80
75
44 170
110 75
42 160
105 50 70
150 W
40
100 65 140 E
25
38 I
95 60 130
10 G
36 5
90 55 120 H
34 T
85 50 110
32 80 45 100
30 90
40
80 35 80
35
W 70 70
30 30
E 60 60
I 25 25
G 50 50
H 20 20
40 40
T 15 15
30 30
10 10
AGE (YEARS) kg
lb kg lb
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Psychosocial Dwarfism DISORDERS OF PITUITARY

Background
GLAND
• Emotional deprivation can cause short stature Introduction
and growth failure • The pituitary gland, located at the base of the
• A good history may reveal a disturbed child– brain, is composed of anterior (i.e., adenohy-
family relationship pophysis) and posterior (i.e., neurohypophy-
sis) regions
Diagnosis
• Origin of the adenohypophysis is from the
• Diagnosis of exclusion
Rathke pouch as an invagination of the oral
Common causes of short stature (Table 12.1) ectoderm
422 A. Morsi
Table 12.1 Common causes of short stature: differences • Soft tissue growth
between constitutional delay, familial short stature, and • Protein synthesis
growth hormone deficiency • Fatty acid release from adipose tissue
Growth • Insulin resistance
Constitutional Familial short hormone
delay stature deficiency
IGF-1
Growth Growth Growth Height or
curve velocity along velocity is length > 3 • IGF-1 is both synthesized in the liver and
or parallel to parallel to but SD below formed locally in bones and muscles of
the lower below the the mean children
percentiles of normal growth • Gene located on chromosome 12
the growth curve
• Circulating IGF-1 is directly related to GH
curve
Family Positive late One or two Depends activity and nutritional status
history bloomers parents are on the
short cause GH therapy (Fig. 12.4)
Bone age Mildly delayed Equal to Delayed • In children with classic GHD, treatment
chronological should be started as soon as possible to ensure
age
the greatest effect on final adult height
Hormonal Normal Normal Low IGF-1
studies and low • Higher doses during puberty can be
IGFBP-3 considered
Treatment Reassurance Reassurance Growth • Maximal response is usually during the 1st
Some may and monitoring hormone year
benefit from
testosterone
short course if
Criteria for discontinuing GH treatment
puberty is • Decision by the patient/parent to discontinue
delayed • Growth rate less than 2 cm/year
IGF-1 insulin-like growth factor 1, IGFBP-3 IGF binding protein 3 • Bone age of 14 years in girls and 16 years in
boys
The major biologically active hormones released
into systemic circulation include the following Adverse effects of GH
• Growth hormone (GH) • Pseudotumor cerebri (headaches and
• Adrenocorticotropic hormone (ACTH) papilledema)
• TSH • Slipped capital femoral epiphysis (limping,
• Luteinizing hormone (LH) and hip or knee pain)
• Follicle-stimulating hormone (FSH) • Gynecomastia
• Prolactin (PRL) • Worsening scoliosis (needs to be monitored)
• Antidiuretic hormone (ADH) • Insulin resistance
Growth hormone (GH) Other indications for GH therapy
• GH is 191-amino acid (191-AA) single-chain 1. Turner syndrome
polypeptide. The GH gene is called GH1 and 2. Noonan syndrome
is located on chromosome 17 3. SHOX-gene mutation
4. Prader–Willi syndrome
Biologic effect of GH
5. Idiopathic short stature
• Linear growth
6. Small for gestational age
• Bone thickness growth
Fig. 12.4 Short stature 2 to 20 years: Boys NAME

secondary to growth hormone Stature-for-age and Weight-for-age percentiles RECORD #
(GH) deficiency. Height
12 13 14 15 16 17 18 19 20
deceleration is noted after 3 years S
of age and weight is not very Date Age Weight Stature BMI* AGE (YEARS) 76 T
much affected. GH therapy 95
190 A
initiated at 11 years of age with 74 T
90
185 U
marked improvement in auxology 72
75
180 R
(http://www.cdc.gov/ E
50 70
growthcharts) 175 MPH
25 68
170
10 66
in cm 3 4 5 6 7 8 9 10 11 5 165
64
160 160
62 62
S 155 155
60 60
T 150 150
A 58
T 145
U 56
140 105 230
R 54
E 135 100 220
52
130 95 95 210
50
125 90 200
48 90
190
120 85
46 180
115 80
75
44 170
110 75
42 160
105 50 70
150 W
40
100 65 140 E
25
38 I
95 60 130
10 G
36 5
90 55 120 H
34 T
85 50 110
32 80 45 100
30 90
40
80 35 80
35
W 70 70
30 30
E 60 60
I 25 25
G 50 50
H 20 20
40 40
T 15 15
30 30
10 10
AGE (YEARS) kg
lb kg lb
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Congenital Hypopituitarism Conditions associated with GHD

Hall–Pallister syndrome
Background • Absence of pituitary gland
• Involves one or more of the six hormones • Hypothalamic hamartoblastoma
secreted by the pituitary gland • Postaxial polydactyly
• Could be isolated GHD (IGHD) or combined • Nail dysplasia
pituitary hormone deficiency (CPHD). Some • Bifid epiglottis
patients start as having IGHD then progress • Imperforate anus
to having CPHD • Anomalies of the heart, lungs, and kidneys
424 A. Morsi
Septo-optic dysplasia Treatment

• Absence of optic chiasm, optic nerve hypo- • Appropriate hormone replacement
plasia, or both
• Agenesis of the septum pellucidum, and
schizencephaly Neonatal Hypoglycemia
• Midfacial anomalies, e.g., solitary maxillary
central incisors, cleft lip/palate Background
• Micropenis/microphallus • Hypoglycemia is the most common meta-
bolic problem in neonates
Clinical presentation • Plasma glucose less than 30 mg/dL in the first
• Neonate 24 h and less than 70 mg/dL thereafter in
–– Hypoglycemia usually severe and persis- newborns. (Point-of- care glucose measure-
tent, with or without seizure ments not diagnostic, needs confirmation
–– Micropenis/microphallus (diagnostic clue with serum level)
in boys; < 2.5 cm stretched in term infants) • Plasma glucose value of less than 50 mg/dL
–– Apnea in children
–– Cyanosis
–– Prolonged neonatal jaundice Causes
–– Most neonates with hypopituitarism have • Transient hypoglycemia
normal length and weight at birth –– Prematurity (low glycogen stores), infant
• Older infants and children of diabetic mother, SGA, perinatal stress,
–– Growth failure is the most common and sepsis
presentation • Inborn errors of metabolism, e.g., carnitine–
–– Delayed tooth eruption acylcarnitine translocase deficiency
–– Central diabetes insipidus may develop or • Glycogen storage disorders
become clinically obvious as they become • Gluconeogenesis disorders
older • Fatty acid oxidation disorders
• Disorders of hormonal regulation of glucose
Diagnosis metabolism:
• Height or length > 3 SD below the mean, fail- –– GHD or hypopituitarism
ure to thrive –– Isolated cortisol deficiency (congenital
• Slow growth velocity (< 5 cm/year) adrenal hyperplasia [CAH)]
• Delayed skeletal age – – Congenital hyperinsulinism (genetic
• Low IGF-1 and low IGFBP-3 defect) is the most common permanent
• Provocative tests: Administration of insulin, cause in the first 3 months of life
arginine, clonidine, or glucagon rapidly • Genetic diseases, e.g., Beckwith–Wiedemann
increases the level of GH in normal children syndrome
–– GH < 10 ng/ml in two provocative tests
with different agents is the usual diagnostic Diagnosis
criteria • Micropenis is a red flag for possible GHD
• Other pituitary hormones must be tested, e.g., • Critical sample should be taken during hypo-
TSH, ACTH, gonadotropins (age-dependent) glycemia (usually if the cause is unknown
• Clinical history (polydipsia, cold water and in persistent cases):
craving) –– Glucose
–– CO2 (chemistry panel) –– Cortisol and growth hormone are counter-

–– Insulin, C-peptide regulatory hormones and are normally ele-
–– Ammonia, lactate vated in response to hypoglycemia
–– GH –– Appropriately suppressed insulin
–– Cortisol (undetectable)
–– Free fatty acids –– Acute treatment is IV dextrose
–– Beta-hydroxybutyrate and acetoacetate –– Long-term management consists of avoid-
(serum ketones) ance of fasting and ensuring adequate
–– Acylcarnitine profile, total and free sugar-containing fluids when ill
carnitine
–– Save serum tube
–– Urine ketones, urine organic acids Craniopharyngioma
• Hypopituitarism or adrenal failure
–– Ketonemia and ketonuria Background
–– Low GH or low cortisol • Most common pituitary tumor: Benign histol-
–– Appropriately suppressed insulin ogy and malignant behavior
• Glycogen storage disease • Persistence of remnants of the original con-
–– Ketonemia and ketonuria nection between the Rathke pouch and the
–– Normal response of GH and cortisol to oral cavity
hypoglycemia • Peak incidence in children aged 5–10 years
–– Appropriately suppressed insulin • More common in males
• Fatty acid oxidation defect or carnitine
deficiency
• Headache
–– No ketonemia and no ketonuria
–– Most common presentation (55–86%)
–– No acidosis
–– Hydrocephalus
–– Appropriately suppressed insulin
• Visual disturbance (37–68%)
• Hyperinsulinism or insulinoma in older
–– Decline of visual acuity
children
–– Constriction of visual fields, bitemporal
–– No ketonemia, no ketonuria
hemianopsia
–– Usually induced by fasting
–– Papilledema
–– Inappropriately elevated insulin concentra-
–– Horizontal double vision
tion (in the presence of hypoglycemia)
• Endocrine dysfunction (66–90%), e.g.,
–– May respond to diazoxide
–– Hypothyroidism (e.g., weight gain, fatigue,
–– Consider multiple endocrine neoplasia
cold intolerance, and constipation)
type 1 (MEN-1) syndrome
–– Diabetes insipidus
• Ketotic hypoglycemia in older children
–– Growth failure and delayed puberty
–– The most common cause of childhood
hypoglycemia and is a diagnosis of Diagnosis
exclusion • Contrast magnetic resonance imaging (MRI)
–– Typical age is 18 months to 5 years with • Magnetic resonance angiography (MRA)
resolution by age 7 years • Complete endocrinologic and neuro-ophthal-
–– Normal physiologic response to hypogly- mologic evaluation with formal visual field
cemia with elevated serum and urine ketone documentation
levels
426 A. Morsi
• Neuropsychological assessment • Failure to thrive

• Intermittent fever
Management
• Surgical removal Diagnosis
• Postsurgical follow-up should be planned in • Serum osmolality > 300 mOsm/kg
1–2 weeks for all patients • Urine osmolality < 300 mOsm/kg
• Appropriate hormone replacement • Hypernatremia
• Urine specific gravity of 1.005 or less and a
urinary osmolality less than 200 mOsm/kg
Diabetes Insipidus (DI) are the hallmarks of DI
• Polyuria and elevated plasma osmolality
Background despite a relatively high basal level of ADH
• DI is defined as the passage of large volumes suggests nephrogenic DI
of dilute urine (< 300 mOsm/kg) • Water deprivation test and response to des-
• Central DI, (neurogenic, pituitary, or neuro- mopressin can differentiate between central
hypophyseal) characterized by decreased and nephrogenic DI
secretion of antidiuretic hormone (ADH; also • If serum osmolality < 270 mOsm/kg and
referred to as arginine vasopressin [AVP]) urine osmolality > 600 mOsm/kg, this will
• Nephrogenic DI, characterized by decreased rule out DI
ability to concentrate urine because of resis- • Suspect primary polydipsia when large vol-
tance to ADH action in the kidney umes of very dilute urine occur with plasma
osmolality in the low–normal range
Cause of central DI
• Trauma or surgery to the region of the pitu- Treatment of central DI
itary and hypothalamus are common causes • Desmopressin
• Neoplasm • Complication is water intoxication; patient
• Infiltration (histiocytosis X) should have water breakthrough every day to
• Infection prevent water intoxication
• Autoimmune • Under most circumstances, water intake
• Congenital should be limited to 1 L/m2/24 h during
antidiuresis
Cause of nephrogenic DI
• Important: Water should always be made
• Congenital X-linked or autosomal dominant
available to the child with DI and intact thirst
• Electrolyte disturbances (hypercalcemia,
mechanism
hypomagnesemia, and hypokalemia)
• Important: Some patients may not have
• Drugs (lithium, demeclocycline, cisplatin,
intact thirst mechanism. They need to be put
amphotericin B, loop diuretics)
on a daily fluid (free water) goal
• Ureteral obstruction, chronic renal failure,
• Infants can also be treated with thiazides and
polycystic kidney disease, Sjogren syndrome,
low solute formulas
and sickle cell anemia
• Psychogenic Treatment of nephrogenic DI
• Thiazide diuretics
• May be combined with amiloride and
• Polyuria
indomethacin
• Irritability
yndrome of Inappropriate ADH

S osmolality < 280 mOsm/kg) and high urine
Secretion (SIADH) osmolality is the hallmark of SIADH
• Hyponatremia and hypo-osmolality resulting • Depends on the severity of hyponatremia and
from inappropriate, continued secretion or chronicity of condition
action of the hormone despite normal or • Correcting hyponatremia too rapidly may
increased plasma volume, which results in result in central pontine myelinolysis with
impaired water excretion permanent neurologic deficits
• Fluid restriction in mild cases
Causes • Administration of 3% hypertonic saline
• Central nervous system (CNS) pathology should be used only in severe and emergent
–– Infection, e.g., tumor, thrombosis, neuro- cases
surgery, hydrocephalus, meningitis, pneu- • The objective is to raise serum Na+ levels by
monia, hypoxia, and brain abscess 0.5–1 mEq/h and not more than 10–12 mEq
–– Head trauma in the first 24 h, to bring the Na+ value to a
• Pulmonary disease maximum level of 125–130 mEq/L
–– Pneumonia, asthma, positive pressure ven-
tilation, tuberculosis, cystic fibrosis
• Neoplastic, e.g., lymphoma and leukemia Cerebral Salt Wasting
• Hypothyroidism
Background
• Excessive treatment of central DI
• Hypersecretion of atrial natriuretic peptides
• Carbamazepine/oxcarbazepine, cyclophos-
phamide, phenothiazines, fluoxetine, vincris- Causes
tine, and cisplatin—important drugs that • Head trauma, hydrocephalus, neurosurgery,
cause SIADH cranial irradiation, hypothalamic/pituitary
• Anorexia neoplasms, cerebral vascular accident, and
• Schizophrenia brain death
Clinical presentation Presentation (Table 12.2)
• Hypervolemic state • Excessive salt wasting
• Depending on the magnitude and rate of • Very high urinary Na+
development, hyponatremia may or may not • Hyponatremia
cause symptoms
• Anorexia, nausea, and malaise are early Diagnosis
symptoms when the serum Na+ level is less • Hypovolemic state (SIADH is euvolemic/
than 125 mEq/L hypervolemic)
• Headache, muscle cramps, irritability, drowsi- • High urine output (SIADH is the opposite)
ness, confusion, weakness, seizures, and coma • Normal or high uric acid
can occur with further decrease in the serum Na • High atrial natriuretic peptide
Diagnosis Treatment
• Hyponatremia (i.e., serum Na+< 135 mmol/L) • Hydration
with concomitant hypo-osmolality (serum • Treatment of underlying cause
428 A. Morsi
Table 12.2 Difference between diabetes insipidus, SIADH, and cerebral salt wasting
Diabetes insipidus SIADH Cerebral salt wasting
Cause Low or resistance to ADH High ADH Unclear pathophysiology; however, may be
associated with increased natriuretic
peptides
Na+ level High Normal or low Low
Serum High Low Low
osmolality
Urine Low High Relatively dilute because of high urine
osmolality output
Intravascular Hypovolemia Euvolemia or Hypovolemia
volume hypervolemia
Urine output High Low High
Urine Na+ Low High or match Very high, more than Na+ intake,
Na intake > 40 mEq/L
Management Allow access to free water all the time + Fluids IV fluids, NS, or even 3% NS
desmopressin or treat for nephrogenic restrictions May need salt supplement
DI
SIADH syndrome of inappropriate ADH secretion, ADH antidiuretic hormone, Na+ sodium, IV intravenous, NS normal
saline, DI diabetes insipidus
• If hyponatremia occurred in < 12 h, rapid cor- • Galactorrhea

rection is required if serum Na+ < 120 mEq/L • Visual disturbance if tumor affects the optic
• Serum Na+ should be raised only enough to chiasm, e.g., bitemporal hemianopsia or total
make patient stable, 0.5 mEq/h (12 mEq/L/24 h) vision loss in severe cases
Diagnosis
• Elevated serum PRL
Hyperpituitarism
• TSH and pregnancy test must be performed
Gigantism and acromegaly • MRI: A serum PRL value of 200 ng/mL or
• Hypersecretion of GH before ossification of greater in the presence of a macroadenoma
the epiphysis causes gigantism and after (> 10 mm) is virtually diagnostic of
epiphyseal closure causes acromegaly prolactinoma
Treatment
Prolactinoma • Bromocriptine
• Cabergoline (bettertolerated than
Background bromocriptine)
• Prolactin-secreting tumor is the most com-
mon cause in adolescents
• Based on its size, a prolactinoma can be classi- THYROID DISORDERS
fied as a microprolactinoma (< 10 mm diame-
ter) or a macroprolactinoma (> 10 mm I ntroduction
diameter)
Location
Clinical presentation • The thyroid gland is found in the neck, below
• Headache the thyroid cartilage (which forms the laryn-
• Amenorrhea geal prominence or “Adam’s apple”)
Function • Large anterior fontanelle

• It produces thyroid hormones, the principal • Associated congenital anomalies; cardiac is
ones being triiodothyronine (T3) and thyrox- the most common
ine, sometimes referred to as tetraiodothyro- • Hypotonia
nine (T4)
• These hormones regulate the growth and rate Laboratory
of function of many other systems in the body • High TSH and low T4
• T3 and T4 are synthesized from iodine and • Low to normal total T4 and TSH within refer-
tyrosine. The thyroid also produces calcito- ence range indicates thyroid-binding globulin
nin, which plays a role in calcium (TBG) deficiency (normal free T4)
homeostasis • If maternal antibody-mediated hypothyroid-
• Hormonal output from the thyroid is regu- ism is suspected, maternal and neonatal anti-
lated by TSH produced by the anterior pitu- thyroid antibodies may confirm the diagnosis
itary, which itself is regulated by • Thyroid ultrasound
thyrotropin-releasing hormone (TRH) pro- • Thyroid scanning (many clinicians treat with-
duced by the hypothalamus out imaging studies)
Treatment
Congenital Hypothyroidism • Levothyroxine given orally is the treatment of
choice
Background • 10 to 15 μg/kg/day initial dose
• Thyroid dysgenesis (aplasia, hypoplasia, or • No liquid preparations of levothyroxine should
an ectopic) is the most common cause of con- be given to neonates or infants. These prepara-
genital hypothyroidism tions are very difficult to keep in suspension,
• Most common form of thyroid dysgenesis is and the delivery of drug is inconsistent
ectopic thyroid • If the newborn screen is positive for hypo-
• Occasionally associated with thyroglossal thyroidism, order TSH and free T4 to con-
cyst firm, then start the treatment immediately,
before the results of the confirmatory tests
Clinical presentation are available
• Most infants are asymptomatic at birth because • No treatment is required for TBG deficiency
of transplacental passage of maternal T4
• Length and weight are normal at birth, but Prognosis
head may be larger at birth • Early diagnosis and treatment of congenital
• Prolongation of physiologic jaundice hypothyroidism prevents severe intellectual
• Poor feeding, especially sluggishness disability and other neurologic complications
• Somnolence and choking spells during feed-
ing may be the first sign in the 1st month
• Respiratory difficulties due to large protruded Thyroid-Binding Globulin Deficiency
tongue, apneic episodes, noisy breathing,
• X-linked condition
nasal obstruction
• Could be partial (1 in 4000) or complete (1 in
• Cold, mottled, and dry skin
15,000)
• Constipation that usually does not respond to
• Heterozygous males are more frequently
treatment
detected
• Umbilical hernia
430 A. Morsi
• Depending on X inactivation, females may

have normal, partial, or complete
deficiency
• T4 and T3 levels are low, TSH is normal, free T4
and free T3 are normal, high T3 uptake (T3U)
• Prognosis: Benign condition → no treatment
needed
Hashimoto, Lymphocytic Thyroiditis

(Autoimmune Thyroiditis)
Background
• Hashimoto thyroiditis is part of the spectrum
of autoimmune thyroid diseases and is char-
acterized by the destruction of thyroid cells
by various cell- and antibody- mediated
immune processes
• The most common cause of hypothyroidism
in the United States in individuals older than
6 years
• Girls 2 to 3 times > boys
• Familial clusters of lymphocytic thyroiditis
are common Fig. 12.5 A 4-year-old female with thyroid enlarge-
ment, fatigue, and daytime somnolence. Thyroid-
Clinical presentation stimulating hormone > 150 mIU/L and free thyroxine 4
• Goiter and growth retardation (most < 0.4 ng/dL. Antithyroid peroxidase antibodies were
common) very high
• Fatigue
• Constipation
–– Peripheral edema of hands and feet, typi-
• Dry skin
cally non-pitting
• Cold intolerance
–– Thickened and brittle nails (may appear
• Hair loss
ridged)
• Weight gain
–– Bradycardia
• Depression, dementia, and other psychiatric
–– Elevated blood pressure (typically diastolic
disturbances
hypertension)
• Decreased school performance
–– Diminished deep tendon reflexes and the
• Menstrual irregularities
classic prolonged relaxation phase
• Galactorrhea
–– Macroglossia
• Other manifestations, depending on the sever-
–– Slow speech
ity of hypothyroidism and other factors, e.g.,
–– Ataxia
age (myxedema)
• In most cases, the thyroid is diffusely large,
–– Puffy face and periorbital edema typical of
firm, and nontender (Fig. 12.5)
hypothyroid facies
• In 30%, the gland is lobular and may seem to
–– Cold, dry skin, which may be rough and
be nodular
scaly
Diagnosis Stepwise approach to a child presenting with

• Thyroid function tests are usually normal elevated TSH
• Elevated TSH and presence of thyroid • It is important to note that children have
autoantibodies, antithyroid peroxidase higher thyroid hormone and TSH level values
(TPO) and antithyroglobulin (TG) antibod- than adults. Hence, it is important to use pedi-
ies, are the best markers of progression to atric reference ranges while interpreting labo-
overt hypothyroidism; however, degree of ratory data
elevation does not predict severity of • TSH has a diurnal variation, with an 8:00 AM
disease measurement being more sensitive in detect-
ing primary hypothyroidism
Management • TSH is obtained to screen for primary hypo-
• If there is evidence of hypothyroidism, levo- thyroidism usually only after a thorough his-
thyroxine can be given tory and physical examination
• Fine-needle aspiration/biopsy (FNAB) of • If TSH is elevated: Thyroid hormone levels
any dominant or suspicious thyroid nod- including total T4 and free T4 levels need to
ules to exclude malignancy or the presence be obtained
of thyroid lymphoma in fast-growing • If TSH is elevated with low free T4 level: An
goiters arbitrary cutoff of 10 uIU/ml or above is gen-
erally used to start therapy with levothyrox-
ine. Levels between 5 and 10 uIU/ml are
Subacute (de Quervain) Thyroiditis considered mild elevations and repeat testing
is indicated
Background
• If TSH is elevated with normal free T4 level
• Subacute thyroiditis is a self-limited disease
(subclinical hypothyroidism), monitoring is
of thyroid gland
warranted with repeat thyroid function every
• Usually occurs after an upper respiratory tract
6 months to 1 year. This scenario is common
infection
in obese children who tend to have mild ele-
Clinical presentation vations in TSH
• Fever
• Thyroid gland tenderness and pain
Graves Disease
Laboratory
Background
• Initially hyperthyroidism (elevated T4 and
• Graves disease is the most common cause of
T3)
hyperthyroidism in pediatric patients
• Followed by more prolonged period of
• An immune-mediated disorder that results from
hypothyroidism
the production of thyroid-stimulating immuno-
Management globulins by stimulated B lymphocytes
• Nonsteroidal anti-inflammatory drugs • These immunoglobulins bind to the TSH
(NSAIDs) for pain receptor to mimic the action of TSH and
• Prednisone in severe cases stimulate thyroid growth and thyroid hor-
mone overproduction
Prognosis
• Almost all patients recover with no thyroid Clinical presentation
problems • Weakness
432 A. Morsi
• Weight loss or muscle wasting –– Might worsen ophthalmopathy

• Diarrhea –– May carry a small risk of malignancy in
• Heat intolerance children
• Pruritus –– Pregnancy must be deferred 6–12 months
• Palpitations and mother cannot breastfeed
• Sleeplessness • Beta-blockers to blunt the toxic effect of the
• Behavioral changes circulating T4 and T3
• Enlarged thyroid, which may cause dyspha-
gia if very large Treatment follow-up
• Exophthalmos usually mild and more com- • Monitor the patient at 6-week to 3-month
mon in adults intervals with thyroid function tests (TSH,
• Upper eyelid retraction total T4/free T4 levels), liver function tests,
• Infrequent blinking (Stellwag sign) and CBC
• Assess other potential adverse effects of the
Laboratory agent by history
• Elevated free T4 and T3
• Suppressed TSH
• Sometimes free T3 is more elevated than T4 Neonatal Thyrotoxicosis
• Antithyroid antibodies (TPO) are often
Background
present
• Due to transplacental transmission of TSH
• Thyrotropin receptor-stimulating immuno-
receptor immunoglobulin from the mother to
globulin (TSI) confirms the diagnosis, and its
the fetus
absence means remission
• To differentiate between Graves disease and Clinical presentation
exogenous thyroid hormone administration, • Irritability
all labs are the same, except thyroglobulin • Flushing
will be low in exogenous thyroid hormone • Tachycardia
and high in Graves disease • Hypertension
• Thyroid enlargement
Treatment • Exophthalmos
• Methimazole is the most common antithyroid
drug used in the United States Diagnosis
• Propylthiouracil (PTU) is the drug of choice • High T4 and T3
in pregnant women with Graves disease • Low TSH
–– Sides effects of antithyroid hormone • Positive TSI
◦◦ Transient urticarial rash (the most com-
mon side effect) Treatment
◦◦ Agranulocytosis (more common in • Mild cases: Symptomatic treatment with a
elderly) beta-blocker (e.g., propranolol)
◦◦ PTU associated with more cases of liver • More severe cases: Antithyroid medications
injuries are necessary
• Radioactive iodine • In very severe cases: Iodides in the form of
–– Permanent hypothyroidism almost Lugol iodine solution or saturated solution of
inevitable potassium iodide (SSKI) are used
Prognosis • More than 95% of thyroid cancers are of thy-

• Usually resolve in 3–12 weeks roid-cell (well-differentiated) origin
• Papillary (subtype) carcinoma is the most
common
Solitary Thyroid Nodules • High rate of regional and distant metastasis
• MEN type 2 is autosomal dominant
Background
• Thyroid nodules are much more likely to Types of thyroid cancers
be malignant in children than they are in • Follicular cell origin
adults –– Papillary cell carcinoma
–– Follicular cell carcinoma
Diagnosis
• Medullary thyroid cancer
• Child’s history, including familial history and
–– MEN type 2
radiation exposure
◦◦ MEN-2A (medullary thyroid
• Thyroid function is usually normal
cancer, hyperparathyroidism, and
• Ultrasonography to determine whether the
pheochromocytoma)
nodule is cystic, solid, or mixed
◦◦ MEN-2B (medullary thyroid cancer,
• FNAB is used for definitive diagnosis (study
pheochromocytoma, and mucosal
of choice)
neuroma)
• FNAB is not necessary or recommended in
the case of toxic nodules
Management • Most childhood thyroid nodules are asymptom-
• All solitary nodules including cold or non- atic and are detected as a neck mass by parents
toxic nodules must be biopsied or by physicians during routine examination
• After initial diagnosis and investigation of the
Diagnosis
thyroid nodule, medical and/or surgical ther-
• Thyroid ultrasound to confirm the presence
apy is decided
of a nodule
• Presumed benign nodule, especially in an
• FNAB is indicated if nodule is suspicious-
adolescent, may simply be observed
looking or is 1 cm or more in diameter
• Close observation and follow-up care are
• Calcitonin level is elevated in medullary thy-
essential
roid cancer
Important to know • Abnormal biochemical labs, e.g., elevated
• Palpable thyroid nodule, more than or equal calcium level (hyperparathyroidism) due to
1 cm on imaging, next step: associated conditions in medullary thyroid
–– Thyroid ultrasound-guided FNAB cancers (MEN type 2)
Management
Thyroid Cancer • TSH suppressive therapy in children with
papillary or follicular-type thyroid cancer
Background • Surgery
• Prior radiation therapy to the neck increases • Radiotherapy
the risk of thyroid cancer • Surveillance
434 A. Morsi
Thyroid Storm (at least 1 h after starting antithyroid drug

therapy)
Background • Consider glucocorticoids to decrease periph-
• Thyrotoxic crisis is an acute, life-threatening, eral conversion of T4–T3
hypermetabolic state induced by excessive
release of thyroid hormones in individuals
with thyrotoxicosis BONE AND MINERAL
Clinical presentation DISORDERS
• Fever (may be the only presenting symptom)
• Profuse sweating ypocalcemia
H
• Poor feeding and weight loss
• Respiratory distress Background
• Fatigue (more common in older adolescents) • Hypocalcemia is defined as a total serum cal-
• Nausea and vomiting cium concentration of less than 8.5 mg/dL in
• Diarrhea children, less than 8 mg/dL in term neonates,
• Abdominal pain and less than 7 mg/dL in preterm neonates
• Jaundice
• Anxiety (more common in older Causes
adolescents) • Early neonatal hypocalcemia (48–72 h of
• Altered behavior birth)
• Seizures –– Prematurity
• Coma –– Birth asphyxia
–– Diabetes mellitus (DM) in the mother
Diagnosis (magnesium depletion in mothers with
• Elevated triiodothyronine (T3), thyroxine DM)
(T4) levels –– IUGR
• Suppressed TSH levels • Late neonatal hypocalcemia (3–7 days after
birth)
Management –– Exogenous phosphate load; this is most
• Patients with thyroid storm should be treated commonly seen in developing countries
in an ICU setting (phosphate-rich formula or cow’s milk)
• Correct electrolyte abnormalities –– Gentamicin use
• Propranolol to minimize sympathomimetic –– Magnesium deficiency
symptoms –– Transient hypoparathyroidism of newborn
• Treat cardiac arrhythmia, if necessary –– Hypoparathyroidism due to other causes
• Aggressively control hyperthermia by apply- • Infants and children
ing ice packs and cooling blankets and by –– Hypoparathyroidism
administering acetaminophen –– Vitamin D deficiency
• Consider methimazole and consult pediatric –– Acquired or inherited disorders of vitamin
endocrinologist D metabolism
• Consider iodine compounds (Lugol iodine or –– Resistance to the action of vitamin D
potassium iodide) orally or via nasogastric –– Liver diseases
tube to block the release of thyroid hormone –– Renal failure
–– Malabsorption ◦◦ Renal failure

–– Pseudohypocalcemia due to hypoalbumin- ◦◦ Hypoparathyroidism
emia –– Low phosphate may indicate
◦◦ Vitamin D abnormalities and rickets
Clinical presentation • PTH levels
• Newborn period –– Hormone studies are indicated if hypocal-
–– Possibly no symptoms cemia persists in the presence of normal
–– Lethargy magnesium and normal or elevated phos-
–– Poor feeding phate levels
–– Vomiting –– Low PTH (or inappropriately normal) lev-
–– Abdominal distension els suggest
• Children, possible presentation ◦◦ Hypoparathyroidism; serum calcium
–– Seizures rises in response to PTH challenge
–– Twitching –– High PTH levels suggest
–– Cramping ◦◦ Vitamin D abnormalities
–– Laryngospasm, a rare initial manifestation ◦◦ Pseudohypoparathyroidism (PHP)
–– Tetany and signs of nerve irritability, such ◦◦ Calcium levels do not rise in response to
as the Chvostek sign, carpopedal spasm, PTH challenge
the Trousseau sign, and stridor • 25-Hydroxyvitamin D and 1,25-
dihydroxyvitamin D
Diagnosis • Urine calcium, magnesium, phosphorus, and
• Total and ionized serum calcium levels creatinine levels
–– A decrease in total calcium can be associ- –– These values should be assessed in
ated with low serum albumin concentration patients with suspected renal tubular
and abnormal pH defects and renal failure. Urine should
• Serum magnesium levels also be evaluated for pH, glucose, and
–– Serum magnesium levels may be low in protein
patients with hypocalcemia, which may • Urine calcium-to-creatinine ratio of more
not respond to calcium therapy if hypo- than 0.3 on a spot sample in the presence of
magnesemia is not corrected hypocalcemia suggests inappropriate
• Severe hypomagnesemia causes hypocalce- excretion
mia by impairing the secretion of and induc- • Serum alkaline phosphatase (ALP) levels
ing resistance to parathyroid hormone (generally elevated in patients with rickets)
• Serum electrolyte and glucose levels
–– Low bicarbonate levels and acidosis may Management
be associated with Fanconi syndrome and • Treatment of the underlying cause
renal tubular acidosis • Treatment of asymptomatic patients with
• Phosphorus levels hypocalcemia remains controversial
–– Phosphate levels are increased in cases of • Hypocalcemia should be treated promptly
exogenous intake in any symptomatic neonate or older child
–– High phosphate may indicate because of the condition’s serious implica-
◦◦ Endogenous phosphate loading tions for neuronal and cardiac function
436 A. Morsi
• Intravenous (IV) infusion with calcium-con- tapping the ipsilateral facial nerve as it
taining solutions can cause severe tissue courses just anterior to the ear
necrosis –– Trousseau sign: Carpal spasm is induced
by inflating a blood pressure cuff around
the arm to a pressure 20 mmHg above
Hypoparathyroidism obliteration of the radial pulse for 3–5 min
Background Diagnosis
• Hypoparathyroidism is a condition of PTH • Primary hypoparathyroidism
deficiency –– Low (or inappropriately normal) PTH and
low calcium level
Causes • Pseudohypoparathyroidism
• Iatrogenic (most common cause), e.g., sec- –– High PTH (due to resistance and PTH
ondary thyroidectomy with accidental receptor mutation) and low calcium
removal of parathyroid glands • Secondary hypoparathyroidism
• Congenital causes, e.g., DiGeorge syndrome –– Low PTH and high calcium level
• Autoimmune polyendocrinopathy–candidia- • Calcium
sis–ectodermal dystrophy (APECED) (aka –– Hypoalbuminemia causes a drop in total
autoimmune polyendocrinopathy syndrome calcium concentration, but the ionized
type 1 [APS 1]) fraction may be within the reference range
• Metal overload, e.g., Wilson disease or –– Alkalosis may trigger symptoms of
hemochromatosis hypocalcemia
• Maternal hypercalcemia in unborn infant may • Serum magnesium
cause suppression of PTH in neonate –– Hypomagnesemia may cause PTH defi-
ciency and subsequent hypocalcemia
–– Exclude it in any patient with primary
• Paresthesias (involving fingertips, toes, peri-
hypoparathyroidism
oral area)
• Serum phosphorus
• Hyperirritability
–– PTH is a phosphaturic hormone. In its
• Fatigue
absence, phosphorus levels in the blood
• Anxiety
rise
• Mood swings and/or personality
• 25(OH)D to exclude vitamin D deficiency as
disturbances
a cause of hypocalcemia
• Seizures (especially in patients with
epilepsy) Management
• Hoarseness (due to laryngospasm) • Correct the hypocalcemia by administering
• Wheezing and dyspnea (due to calcium and vitamin D (calcitriol)
bronchospasm)
• Muscle cramps, diaphoresis, and biliary colic
• Hypomagnesemia, hypokalemia, and alkalo- Pseudohypoparathyroidism (PHP);
sis (e.g., hyperventilation), which worsen Albright Hereditary Osteodystrophy
signs and symptoms of hypocalcemia
(AHO)
• Hypocalcemia may be demonstrated at the
bedside by eliciting the following signs: Background
–– Chvostek sign: Facial twitching, especially • PHP is a heterogeneous group of disorders
around the mouth, is induced by gently characterized by hypocalcemia, hyperphos-
phatemia, increased serum concentration of • Skeletal defect/normal PTH/normal Ca/

PTH, and insensitivity to the biological activ- normal phosphate is pseudopseudohypopara-
ity of PTH thyroidism
Genetic defect Management

• PHP IA • All patients with severe symptomatic hypo-
–– Account for majority of patients calcemia should be initially treated with IV
–– It is a resistance to PTH calcium
–– Genetic defect of the alpha subunit of stim- • Administration of oral calcium and 1 alpha
ulatory guanine nucleotide-binding pro- hydroxylated vitamin D metabolites, such as
tein. This factor is required for PTH bound calcitriol, remains the mainstay of treatment
to cell surface receptors to activate cyclic
adenosine monophosphate (cAMP)
–– It is inherited as autosomal dominant trait Familial Hypocalciuric
• PHP IB Hypercalcemia (Familial Benign
–– Affected patients have normal level of G Hypercalcemia)
protein activity and a normal phenotype
appearance Background
–– These patients have tissue-specific resis- • Autosomal dominant condition of benign
tance to PTH but not to other hormones hypercalcemia
• PHP II • Asymptomatic
–– Rare • Usually discovered incidentally on routine
–– Normal phenotype appearance (no AHO) labs

• Hypocalcemia can present in infancy • Hypercalcemia with calcium level > 10.2 mg/
• Tetany dL
• Albright hereditary osteodystrophy (AHO; • Urine calcium to creatinine ratio < 0.01 and
PHP type 1A) characterized by: urine calcium < 200 mg/day
–– Short stature • Normal PTH and normal phosphate
–– Stocky habitus
–– Round face Treatment
–– Brachymetacarpals (particularly the fourth • None
and fifth digits)
–– Dimpling over the knuckles of a clenched
fist due to short metacarpals Hyperparathyroidism
–– Brachymetatarsals
Background
–– Intellectual disability
• Hyperparathyroidism is rare in children
–– Subcutaneous calcifications
• Primary hyperparathyroidism is caused by a
Diagnosis single adenoma and is the most common
• High serum PTH/low serum Ca/high phos- cause
phate/skeletal defect is a classic finding in • Familial cases can occur as part of the MEN
Albright hereditary osteodystrophy syndromes (MEN-1 or MEN-2A)
• High serum PTH/low serum Ca is either PHP • Secondary hyperparathyroidism can occur
or secondary hyperparathyroidism with chronic renal failure, cholestatic liver dis-
ease, or as an iatrogenic effect, e.g., lithium
438 A. Morsi
Clinical presentation Vitamin D metabolism

• Commonly presents without symptoms • Cholecalciferol (i.e., vitamin D-3) is formed
• Hypercalcemia in the skin from 5-dihydrotachysterol
• Muscular weakness • First hydroxylation step occurs in the liver
• Bone pain (position 25)
• Abdominal pain • Produces calcidiol (aka 25-hydroxycholecal-
• Acute pancreatitis ciferol or 25-hydroxyvitaminD) or 25(OH)D
• Nephrolithiasis –– 25(OH)D is the best indicator of overall
vitamin D status and commonly tested
Diagnosis • Second hydroxylation step occurs in the kid-
• Serum calcium usually > 12 mg/dL ney (position 1)
• Low serum phosphorus < 3 mg/dL –– Calcitriol (1,25-dihydroxycholecalciferol)
• High PTH is active metabolite
• Normal calcitonin level –– Calcitriol acts at three known sites to
tightly regulate calcium metabolism:
Management ◦◦ Promotes absorption of calcium and
• For primary hyperparathyroidism, subtotal or phosphorus from the intestine
total parathyroidectomy is the most common ◦◦ Increases reabsorption of phosphate in
choice for adults or children the kidney
• Calcitriol may help in cases with chronic ◦◦ Acts on bone to release calcium and
renal failure phosphate
• Treatment of acute severe hypercalcemia: Ca • Calcitriol
> 14 mg/dL –– Increases calcium and phosphorus in extra-
–– IV hydration cellular fluid
–– Loop diuretics (e.g., furosemide) after –– Increases calcification of osteoid, primar-
hydration ily at the metaphyseal growing ends of
–– Hemodialysis in severe cases bones
• Parathyroid hormone (PTH)
–– PTH facilitates the 1-hydroxylation step in
RICKETS vitamin D metabolism in the kidney
–– In the vitamin D deficiency state, hypocal-
Vitamin D Deficiency Rickets cemia develops, which stimulates excess
secretion of PTH
Background –– In turn, renal phosphorus loss is enhanced,
• Disease of growing bone that is unique to further reducing deposition of calcium in
children and adolescents the bone
• Caused by a failure of osteoid to calcify in a –– Excess PTH also produces changes in the
growing person. Failure of osteoid to calcify bone similar to those occurring in
in adults is called osteomalacia hyperparathyroidism
• Vitamin D deficiency rickets occurs when the –– Early in the course of rickets, the calcium
metabolites of vitamin D are deficient concentration in the serum decreases. After
• Less commonly, a dietary deficiency of cal- the parathyroid response, the calcium con-
cium or phosphorus may also produce centration usually returns to the reference
rickets range, though phosphorus levels remain low
The Effects of Rickets
Open fontanelle
Soft skull bone (craniotabes)
Delayed teething
Rickety rosary and Harrison sulcus

Wide Elbow Joints
Wide Wrist Joints
Bowlegs Wide knee joints
Wide Ankle Joints
Fig. 12.6 Skeletal manifestations of rickets
• Alkaline phosphatase Clinical presentation (Fig. 12.6)

–– Produced by overactive osteoblast cells • At very young ages, vitamin D deficiency is
–– Usually very high levels in growing children more likely to present as hypocalcemia than
as rickets
Causes of rickets • Muscular hypotonia
• Nutritional deficiency still the most common • Craniotabes (areas of thinning and softening
cause of rickets worldwide of the bones of the skull)
• Prolonged and exclusive breastfeeding with- • Frontal bossing and delays the closure of the
out vitamin D supplementation with minimal anterior fontanelle
sunlight exposure • Bowlegs and knock knees on weight limbs
• Intestinal malabsorption of fat • Rachitic rosary along the costochondral
• Liver or kidney disease junctions
• Anticonvulsant drugs (e.g., phenobarbital, • Harrison groove due to weakened ribs pulled
phenytoin) by muscles also produces flaring over the
• Accelerate metabolism of 25(OH)D diaphragm
• Vegan diets, especially lacto-vegans • Kyphoscoliosis in older children
• Genetic defects
440 A. Morsi
• Knobby deformity of long bone, which is –– High-dose vitamin D may need to be inter-
visualized on radiography as cupping and mittently repeated (usually every 3 months)
flaring of the metaphyses if poor compliance persists with mainte-
• Marfan sign; palpation of the tibial malleolus nance dosing
gives the impression of a double epiphysis • Calcium replacement
• Greenstick fracture –– Hypocalcemia should be treated with cal-
cium supplements
Diagnosis (Table 12.3) –– Parenteral calcium as calcium gluconate
• Low to normal calcium becomes necessary in case of tetany or
• Low phosphorus convulsions
• High alkaline phosphatase –– Calcitriol may be necessary until calcium
• High PTH levels normalize
• Low 25(OH)D • Monitoring therapy
• Low to high 1,25-dihydroxyvitamin D –– It is important to obtain calcium, phospho-
• Normal HCO3 rus, and ALP levels 1 month after initiating
therapy
Radiography (Fig. 12.7)
• Anterior view of the knee is the best site to
study, also the wrist and ankle
• Widening and cupping of the metaphysis
• Fraying of metaphysis a b
• Epiphyseal plate is widened and irregular
• Osteopenia
Management
• Indication for treatment
–– Vitamin D therapy is necessary for infants
and children who manifest clinical features
of hypocalcemia as a result of vitamin D
deficiency or rickets and when vitamin D
levels are in the deficient range
• Vitamin D and calcium replacement
–– Vitamin D given daily for a 2- to 3-month
period to normalize 25(OH)-D levels and
replenish stores
–– Vitamin D3 can be given 2000 IU PO daily
or 50,000 IU PO weekly for 6 weeks
–– With therapy, radiologic evidence of healing is
observed in 2–4 weeks, after which the dose of
vitamin D can be reduced to 400 IU/day
–– Lack of compliance is an important cause of
lack of response, and an option after the 1st
month of life is to administer high doses of
vitamin D in a single administration as “stoss
therapy,” instead of smaller doses over a lon- Fig. 12.7 Radiographs of rickets. Radiographs of the wrist
(a) and leg (b) of a 3-year-old boy with nutritional rickets
ger period, followed by maintenance dosing showing the cupping, fraying, and widening of the physis
–– With stoss therapy, a biochemical response Clinical presentation

occurs in 1 or 2 weeks, the first sign of • Failure to thrive
which is an increase in phosphate • Hypotonia
–– It is important to remember that ALP levels • Reluctance to bear weight when beginning to
may actually increase in the short term as stand or walk
bone formation rates increase • Delayed dentition
–– Complete radiologic healing may take
months, but changes are evident in 1 week Diagnosis
–– In 3 months, it is important to obtain cal- • Normal calcium level
cium, phosphate, magnesium, ALP, • Low phosphorus
25(OH)D, and PTH levels, and one may –– Concentration reference range for infants
consider obtaining a urine sample to deter- (5.0–7.5 mg/dL) is high compared with
mine the calcium/creatinine ratio that for adults (2.7–4.5 mg/dL), e.g.,
–– A radiograph should also be repeated at 3 mg/dL is considered low in young
3 months children
–– 25(OH)D levels should be monitored yearly –– Hypophosphatemia can easily be missed in
• When to refer an infant
–– If radiographic evidence of some healing is • Very high ALP (significantly high)
not observed with vitamin D and calcium • Normal HCO3
replacement in 3 months –– HCO3 is low in Fanconi syndrome or ocu-
–– Considerations should include malabsorp- locerebrorenal dystrophy (Lowe syn-
tion, liver disease, or a lack of compliance drome), i.e., non-anion gap metabolic
with replacement therapy acidosis
–– Important to remember: Normal levels of ALP • Radiography
and 25(OH)D; very low or very high levels of –– Same as vitamin D deficiency rickets
1,25- dihydroxyvitamin D; and high serum
urea nitrogen and creatinine levels are red Management (Table 12.3)
flags for considering other causes of rickets • Calcitriol and phosphorus
(e.g., inherited forms of hypophosphatemic
rickets and vitamin D receptor mutations)
• Orthopedic referral if severe deformities have DISORDERS OF PUBERTY
occurred
General considerations
Prevention of vitamin D deficiency • Positive relation between degree of obesity and
• Supplementation with 400 IU of vitamin D early puberty has been reported (African-
should be initiated within days of birth for all American and Hispanic populations
breastfed infants especially)
• Appropriate exposure to sunlight • Delayed puberty is common in gymnasts and
marathon runners (lack critical adiposity)
Hypophosphatemic Rickets
(X-Linked) Normal Variants of Puberty:
Premature Adrenarche
Background
• X-linked hypophosphatemic rickets is an Background
X-linked dominant disorder • Benign, self-limited
• Affects both males and females • Onset before age 6 years
442 A. Morsi
Table 12.3 Types of rickets, differential diagnosis, and common laboratory findings
25(OH)
Disorder Defect Ca Ph PTH D Calcitriol ALP Treatment
Vitamin D deficiency Decreased vitamin D N, L H L N, L, H H Vitamin D
L
1-αhydroxylase mutation 25-(OH)D cannot be N, L H N Very L H Calcitriol
converted to calcitriol L
Vitamin D receptor End-organ resistance to N, L H N Very H H Ca
mutation resistance vitamin D L
Chronic renal failure Decrease activity of N, H Very N L H Ca and phosphate
1-αhydroxylase in the L H binders
kidney
Hypoparathyroidism Low PTH L H L N N N Ca, vitamin D, and
calcitriol in some
cases
X-linked hypophosphatemic Proximal tubular defect, N, L N, H N N, H Phosphate and
rickets Ph wasted in the urine L slightly L calcitriol
Mostly due to PHEX
mutation
Pseudohypoparathyroidism PTH resistance L H H N N N Ca and vitamin D
(Gsα mutation)
Fanconi syndrome RTA N L N N Slightly L H Phosphate,
or H calcitriol, or
1α-hydroxy vitamin
D3
Ca calcium, Ph phosphorus, PTH parathyroid hormone, 25(OH)D 25-hydroxyvitamin D, ALP alkaline phosphatase, N normal, H high, L low, RTA
renal tubular acidosis
Clinical presentation I solated (Benign) Premature

• Early pubic hair and axillary hair Thelarche
development
• Increased sebaceous activity Background
• Adult-type body odor • Premature thelarche refers to isolated breast
• No sexual development (breast buds in girls; development that occurs in the first 2 years of
testicular enlargement in boys) life
• Normal growth pattern • Possible underlying cause must be investi-
gated if it occurs after 3 years of age
Diagnosis
• Bone age approximates chronological age or Diagnosis
mildly advanced • Normal bone age
• Other imaging studies are normal • No other signs of puberty
• Slight increase in DHEA-S level • No growth acceleration
• Other adrenal steroid hormones are normal • All labs are normal for age
• Normal sex hormones • Unilateral or bilateral with waxing and wan-
• No CAH ing course
• Consistent with prepubertal pattern • Regression usually occurs within 18 months
but may persist for 3–5 years
Management • Regression might not happen if presenting
• Reassurance breast development is > Tanner II
Management the pituitary gonadotrophs to release LH and

• Benign condition and self-limited FSH, which stimulate the gonads to release
• However, patients should be followed at 3- to sex hormones (gonadarche: estrogen from
6-month intervals, as studies have indicated ovaries and testosterone from testes)
that about 18% of premature thelarche will • First manifestation of gonadarche in boys is
progress to central PP testicular enlargement (> 3 ml in volume) and
• Thelarche after the first 3 years of life must be in girls is breast budding (Tanner II)
investigated • Normal pubertal timing (gonadarche) is
between 8 and 13 years in girls and 9 and
14 years in boys
Premature Menarche • Pubertal signs are considered precocious if
they happen before the age of 8 years in girls
Background and 9 years in boys
• Premature menarche by itself is very rare • PP can be classified as gonadotropin-depen-
dent (centrally mediated) and gonadotropin-
Differential diagnosis independent (peripherally mediated)
• Foreign bodies
• Vulvovaginitis
• Sexual abuse Sexual Maturity Ratings (SMRs)
Clinical presentation Sexual development in boys (Fig. 12.8, and

• Most girls with isolated premature menarche Table 12.4)
have only 1 to 3 episodes of bleeding, then • Thinning of scrotum
puberty occurs at normal time • Increased pigmentation of scrotum
• Enlargement of testis > 3 ml or 2.5 cm
Diagnosis • Pubic hair
• Gonadotropin levels are normal • Height acceleration occurs late at SMR 4–5
• Estrogen may be elevated (typically age 13–14)
• Ovarian cyst may be noted Sexual development in girls (Fig. 12.9, and
Table 12.5)
Precocious Puberty (PP) • Breast buds
• Pubic hair
Definitions • Height acceleration peak during SMR 2–3
• Thelarche: Breast development (typically 11–12 years)
• Adrenarche: Maturation of adrenal androgen • Menarche takes usually 2–2.5 years after
production leading to body odor, acne, axil- breast development but can take up to
lary and pubic hair development 6 years
• Pubarche: Pubic hair development; usually
part of adrenarche
• Menarche: First vaginal bleeding Differential Diagnosis for Precocious
• Gonadarche: Earliest gonadal changes in Puberty
response to pituitary gonadotropins
A. Gonadotropin-dependent PP = centrally
Background mediated PP
• The hypothalamus releases gonadotropin- • Idiopathic = most common cause
releasing hormone (GnRH), which stimulates • CNS disorders
444 A. Morsi
Table 12.5 Sexual maturity rating in girls
I 3* < 2.5 Stages Pubic hair Breasts

cm 1 Prepubertal: no pubic Prepubertal: Juvenile
hair present, fine hair breast with small flat
may be noted areola and elevated papilla
4* 2.5 - 3.2
II 2 Sparse, lightly Small mound and areolar
cm
pigmented diameter increases
3 Increased in amount Breast and areola are
III
10* 3.0 and becomes darker, larger, no separation of
cm starting to curl breast contour is noted
4 Abundant, coarse, Areola and papilla form
curly, but less than secondary mound,
IV 16* 4.1 - 4.5
adult separation from contour is
cm
noted
5 Adult female triangle, Mature, more projection of
4.5 extends to medial papilla, areola becomes
V 25*
cm thigh part of general breast
* = ml contour
Fig. 12.8 Sexual maturity rating in boys –– Hypothalamic hamartomas: Most common
identified CNS lesion. Benign and usually
Table 12.4 Sexual maturity rating in boys
requires no intervention
Stages Pubic hair Genitalia –– Tumors (e.g., astrocytoma, gliomas, germ
1 Prepubertal Prepubertal
2 Sparse, lightly Scrotum and penis enlarge
cell tumors secreting human chorionic
pigmented at the slightly gonadotropin [HCG])
base of the penis –– Acquired CNS injury caused by inflamma-
3 Begins to curl, Testes and scrotum continue tion, surgery, trauma, radiation therapy, or
extend laterally to grow abscess
4 Coarse, curly, adult Large and darker scrotum,
type but less in penis becomes large and • Congenital anomalies (e.g., hydrocephalus,
quantity increased in width, glans arachnoid cysts, suprasellar cysts)
penis develops • Genetic mutations: e.g., MKRN-3, DLK-1,
5 Adult distribution Adult size scrotum and penis KISS1, KISSR1
and extends to
• Syndromes, e.g., neurofibromatosis type 1
medial thigh
B. Gonadotropin-independent PP = peripher-
ally mediated PP
I • Gonads
–– McCune Albright syndrome (see below)
–– Testotoxicosis (familial male gonadotropin-
II
independent PP)
–– Tumors (e.g., theca cells, granulosa cells,
III
Leydig cells, Sertoli cells)
• Adrenal gland
–– CAH (see below)
IV –– Tumors (adenoma or carcinoma)
• HCG-secreting tumors, e.g., hepatoblastoma
(HCG acts as a gonadotropin)
V • Exogenous exposure to estrogen or testoster-
one or endocrine disruptor chemicals
• Severe primary hypothyroidism (= Van Wyk–
Fig. 12.9 Sexual maturity rating in girls
Grumbach syndrome)
C. Gonadotropin-dependent PP = centrally Gonadotropin-independent PP = peripherally

mediated mediated PP
• PP increases the risk for psychological and • Clinical presentation and management will
social stress, including sexual abuse and com- depend on the underlying cause
promise of final adult height in untreated • Random and GnRH-stimulated levels of
cases gonadotropins are suppressed with elevated
sex hormone levels
Clinical presentation • Adrenal androgens can be measured, includ-
• PP in girls < 8 years ing DHEA- S, androstenedione, and
–– Breast enlargement, which may initially be 17-hydroxyprogesterone
unilateral • Thyroid functions should be measured in all
–– Pubic and axillary hair may appear first patients presenting with signs of PP to rule
–– Accelerated linear growth and bone age out severe primary hypothyroidism
advancement • Ultrasound or imaging of gonads/adrenals
• PP in boys < 9 years may be needed
–– Testicular enlargement, a subtle finding
that often goes unnoticed by patients and
parents McCune–Albright Syndrome
–– Growth of the penis and scrotum
–– Accelerated linear growth and bone age Background
advancement • Caused by an activating mutation of the
GNAS gene
Diagnosis • Characterized by the following triad:
• Random gonadotropin and sex hormones –– Polyostotic fibrous dysplasia
may be elevated; however, in many occa- –– Café-au-lait skin pigmentation
sions, random measurements are not –– Gonadotropin-independent PP
diagnostic
• Definitive diagnosis of central PP may be Clinical presentation
confirmed by measuring LH (by ultrasensi- • PP
tive assay) levels 60 min after stimulation –– Breast development
with a parenteral injection (subcutaneous or –– Vaginal bleeding (may occur before breast
IV) with a short-acting GnRH analog development)
• Bone age radiograph is a quick and helpful –– Genital maturation (with or without pubic
means to estimate the likelihood of PP and its hair growth)
speed of progression – – Increased height velocity and advanced
bone age
Management – – Macro-orchidism
• MRI of the brain is indicated in all boys (any • Café-au-lait pigmentation
age) with central PP and in girls with onset –– Segmental distribution
less than 6 years of age. There is no consen- –– Frequently predominating on one side of
sus on ordering MRI brain for girls between 6 the body without crossing the midline
and 8 years of age • Polyostotic fibrous dysplasia
• Long-acting GnRH analogs are the standard –– Multiple pathologic fractures
of care for central PP. They act by inhibiting –– Gait anomalies
the hypothalamic–pituitary–gonadal axis –– Visible bony deformities (including abnor-
• Treatment of the cause, e.g., surgical resec- mal bone growth of the skull), bone pain,
tion of tumor and irradiation and joint stiffness with pain
446 A. Morsi
• Other signs of GNAS activation: e.g., hyper- • Central causes or hypogonadotropic

thyroidism or hypercortisolism hypogonadism
–– Congenital causes
Diagnosis ◦◦ Kallmann syndrome (delayed puberty
• Elevation of sex hormones (estrogen in girls and anosmia (loss of smell sensation)
and testosterone in boys) with suppressed ◦◦ Bardet–Biedl syndrome
gonadotropins (both random and GnRH ana- ◦◦ Prader–Willi syndrome
log stimulated) ◦◦ Congenital panhypopituitarism
• Plain radiography can show multiple patchy –– Acquired causes: Tumors, radiation, or
areas of bony lysis surgery affecting the hypothalamus and/or
pituitary gland
Management • Primary gonadal failure or hypergonado-
• No specific treatment for this syndrome tropic hypogonadism, e.g., Turner syndrome
• Treatment of PP and Klinefelter syndrome
–– Aromatase inhibitors
Primary Hypogonadism
Delayed Puberty
Causes
• In boys, puberty is considered delayed if tes- • Primary hypogonadism in males or vanishing
ticular volume is less than 4 ml by 14 years of testis syndrome
age or if started before 14 years of age and is • Developmental anomalies associated with the
taking more than 5 years to complete genital system (e.g., hypospadias, micrope-
• In girls, puberty is considered delayed if no nis, and cryptorchidism)
breast development is happening by 13 years • Mumps orchitis, trauma, radiation exposure
of age or if no menarche by age 16 years or of the head or testes, and chemotherapy can
3 years after breast budding cause testicular failure
• Spironolactone, cyproterone, marijuana, her-
Differential diagnosis of delayed puberty
oin, and methadone can inhibit the synthesis
includes the following
of testosterone
• Constitutional delay of growth and puberty
• Klinefelter syndrome
(normal variant of normal pubertal timing)
–– The most common cause of delayed puberty Clinical presentation
–– Positive family history is usually present • In male infants, the testicles are abnormally
• Functional disorders and chronic systemic small
illness • Failure to develop secondary sexual
–– Chronic illnesses characteristics
–– Nutrition disorders, e.g., malnutrition, • Eunuchoid body habitus
anorexia nervosa, etc.
–– Endocrinopathies Diagnosis
–– Psychological stress • Elevated FSH and LH
–– Medications, e.g., steroids
Klinefelter Syndrome (See Also • Presence of a rubbery or firm mass extending

Chap. 4 “Genetic Disorders”) concentrically from the nipples
• Gynecomastia should be differentiated from
Background pseudogynecomastia (lipomastia), which is
• Most common major sexual differentiation characterized by fat deposition without glan-
abnormality dular proliferation
• 47,XXY karyotype • Common in adolescence
• Abnormalities of nondisjunction during meiosis
Causes
Clinical presentation • Estrogen–androgen imbalance
• Gynecomastia • Pubertal (physiologic gynecomastia)
• Male breast cancer • Klinefelter syndrome
• Mild intellectual disability • Testicular tumor
• Small penis • Ectopic production of HCG, e.g., germ cell
• Testes are small and firm (usually < 2 cm or tumor
2 ml) • Chronic liver disease
• Azoospermia • Hyperthyroidism
• Decreased facial hair, but the pubic hair is • Adrenal tumor
abundant • Familial gynecomastia
• Prolactinoma
Diagnosis
• Karyotype Approach and considerations
• Elevated FSH and LH • Asymptomatic and pubertal gynecomastia
• Low inhibin B level does not require further tests and should be
• Increased estradiol to testosterone ratio reevaluated in 6 months
• Red flags
Management –– Breast size greater than 5 cm
• Testosterone replacement after age 11 years (macromastia)
(intramuscular [IM], or transdermal) –– A lump that is tender, of recent onset, pro-
–– Testosterone 25–50 mg IM every 3–4 weeks gressive, or of unknown duration
–– Increase the dose by 50 mg every –– Signs of malignancy (e.g., hard or fixed
6–9 months lymph nodes or positive lymph node
–– Goal: 200–250 mg every 3–4 weeks findings)
• Breast cancer surveillance • Further investigation if abnormal underlying
cause is considered
Gynecomastia Treatment
• Generally, no treatment is required for physi-
Background ologic gynecomastia
• Gynecomastia is a benign enlargement of the • Pubertal gynecomastia resolves spontane-
male breast (usually bilateral but sometimes ously within several weeks to 3 years in
unilateral) resulting from a proliferation of approximately 90% of patients
the glandular component of the breast
448 A. Morsi
Turner Syndrome (See also Chap. 4 • Treatment can be started with continuous
“Genetic Disorders”) low-dose estrogens at 12 years
• These can be cycled in a 3-weeks on, 1-week
Background off regimen and after 6–18 months; progestin
• More than 95% of adult women with Turner can be added later
syndrome are short and infertile
• 45,X chromosome
ADRENAL DISORDERS
• Short stature
• Ovarian failure For the purpose of this review, the following disor-
• Heart murmur ders will be discussed:
–– Bicuspid aortic valve (most common heart • Disorders of the adrenal cortex: Cushing syn-
defect) drome, Addison disease, and hyperaldoste-
–– Coarctation of the aorta ronism. CAH syndrome will be discussed
• Hypertension under disorders of sexual differentiation
• Lymphedema at birth • Disorders of the adrenal medulla:
• Webbed neck Pheochromocytoma
• Madelung deformity
• Hypothyroidism
Cushing Syndrome
Diagnosis
Background
• Karyotype: Diagnosis is confirmed by the
• Caused by prolonged exposure to elevated
presence of a 45,X cell line or a cell line with
levels of either endogenous glucocorticoids
deletion of the short arm of the X chromo-
or exogenous glucocorticoids
some (Xp deletion), also mosaic forms
• Exogenous glucocorticoid exposure is the
• The buccal smear for Barr bodies is
most common overall cause. ACTH therapy
obsolete
is another cause of hypercortisolism but is
• Y-chromosomal material should be investi-
much less common
gated for possibility of mixed 45,X/46,XY
• Endogenous causes
mosaicism may have mixed gonadal dysgen-
–– ACTH-secreting pituitary adenoma
esis and are at a high risk for
◦◦ Most common endogenous cause (75%)
gonadoblastoma
◦◦ More common above 7 years of age
• LH and FSH rise to menopausal level after
–– Adrenal causes of Cushing (adenoma, car-
age of 10 years
cinoma, and bilateral hyperplasia)
• TSH and thyroid study must be followed due
◦◦ More common below 7 years of age
to high risk of hypothyroidism
–– Ectopic ACTH-secreting tumors represent
Management less than 1% of cases and is very rare in
• GH to improve final height children
• Estrogen replacement therapy is usually • Cushing syndrome causes can be classified as
required ACTH-dependent (Cushing disease and ecto-
• Estrogen is usually started at age 12–15 years pic secretion) and ACTH-independent (exog-
after height optimized enous exposure or adrenal causes)
Clinical presentation • Children with Cushing syndrome (and other

• Excessive weight gain, especially in the face endocrine causes of short stature) are obese
(moon facies), supraclavicular region, upper and short
back (buffalo hump), and torso
• Failure to grow or short stature
• Hypertension yperaldosteronism
H
• Purple stretch marks, easy bruising, and other
signs of skin thinning Background
• Proximal muscle weakness • Rare in children
• Depression, cognitive dysfunction, and emo- • Primary hyperaldosteronism usually due to
tional lability may develop adrenal tumor
• Hypertension • Secondary hyperaldosteronism, e.g.,
• DM or glucose intolerance nephrotic syndrome, congestive heart failure,
• Decreased bone density and fractures and liver cirrhosis
Diagnosis
• Hypertension
• Evidence of hypercortisolism
• Headache
–– Elevated 24-h urinary free cortisol
• Hypokalemia-related symptoms, e.g., consti-
–– Low-dose dexamethasone suppression test
pation and weakness
showing no suppression of 8:00 AM cortisol
–– Loss of normal circadian rhythm, i.e., ele- Diagnosis
vated cortisol at midnight • Primary hyperaldosteronism
• If there is evidence of hypercortisolism → –– Elevated aldosterone level
ACTH levels will be elevated in Cushing dis- –– Low renin level
ease and ectopic secretion and will be low in –– Hypertension
adrenal causes –– Hypokalemia
• Imaging is recommended: e.g., brain MRI to • Secondary hyperaldosteronism
look for Cushing disease (pituitary) and –– Elevated plasma renin activity (PRA)
abdominal CT for adrenal causes
• Nonspecific laboratory evidence: Elevated Management
white blood cell count greater than 11,000/ • Surgical removal of adenoma
mm3, hyperglycemia, and hypokalemic meta- • Prednisone for glucocorticoid-suppressible
bolic alkalosis hyperaldosteronism
Management
• Depends on lesion and location Adrenal Insufficiency
• Unilateral adrenalectomy for benign adrenal
tumor • Can be classified into primary adrenal
• Treatment of choice for pituitary adenoma: insufficiency and secondary or central
Transsphenoidal pituitary microsurgery adrenal insufficiency
• The most common cause of primary adrenal
Remember insufficiency is autoimmune adrenal insuffi-
• Children with obesity are usually tall ciency, also known as Addison disease
450 A. Morsi
• The most common cause of secondary/cen- • Failure to increase steroids in patients with adre-
tral adrenal insufficiency is chronic use of nal insufficiency in time of stress, e.g., surgery
exogenous supraphysiological doses of corti-
costeroids (iatrogenic adrenal insufficiency) Clinical presentation
• It is important to note that chronic use of cor- • Hyperpigmentation
ticosteroids will inhibit ACTH secretion with –– Caused by the stimulant effect of excess
resulting adrenal gland atrophy adrenocorticotropic hormone (ACTH) on
• Sudden cessation or withdrawal of corticoste- the melanocytes to produce melanin
roids in these patients will lead to acute adre- • Vitiligo
nal insufficiency or crisis • Hypotension
• A similar scenario will happen if the patient • Myalgias and flaccid muscle paralysis may
is on physiological doses of steroids but is occur due to hyperkalemia
exposed to stress (e.g., surgery, illness) with • Acute adrenal crisis
no additional replacement –– Nausea, vomiting, and vascular collapse
–– Shock; may appear cyanotic and confused
–– Acute abdomen
Addison Disease –– Hyperpyrexia, with temperatures reaching
105 °F or higher
Background –– In acute adrenal hemorrhage, the patient is
• Addison disease is adrenocortical insuffi- usually in an acute care setting, deterio-
ciency due to the destruction or dysfunction rates with sudden collapse, abdominal or
of the entire adrenal cortex flank pain, and nausea with or without
• Idiopathic autoimmune Addison disease hyperpyrexia
tends to be more common in females and
children Diagnosis
• High-dose ACTH stimulation test (Cortrosyn,
Associated autoimmune diseases cosyntropin, or Synacthen)
• Diabetes mellitus (DM) type 1 • Low cortisol with elevated ACTH suggestive
• Celiac disease, Hashimoto thyroiditis • Hyponatremia
• Graves disease • Hyperkalemia
• Vitiligo • Mild non-anion-gap metabolic acidosis due
• Alopecia areata, totalis, and universalis to the loss of the sodium-retaining and potas-
• Premature ovarian or testicular failure sium and hydrogen ion-secreting action of
• Pernicious anemia aldosterone
• Autoimmune polyglandular syndrome (APS)
type 2 Management of adrenal crisis
• In stress situations, the normal adrenal gland
Other causes output of cortisol is approximately 100 mg/
• Tuberculosis, sarcoidosis, histoplasmosis, m2 of bovine serum albumin (BSA) in 24 h
blastomycosis, and cryptococcosis could • IV access should be established urgently
involve the adrenal glands • Infusion of isotonic NaCl to restore volume
deficit and correct hypotension
Acute Addison Disease • IV bolus of hydrocortisone and then 100 mg/
m2/day divided into three or four times a day
Causes until resolution of crisis, then consult endo-
• Bilateral adrenal hemorrhage, e.g., crinology to discontinue or taper
meningococcemia
Pheochromocytoma • Nitroprusside should also be used for uncon-

trolled hypertension
Background
• Rare catecholamine-secreting tumor that
arises from chromaffin cells of the sympa- Polycystic Ovarian Syndrome (PCOS)
thetic nervous system (adrenal medulla and
sympathetic chain) Background
• Women with PCOS have abnormalities in the
Clinical presentation metabolism of androgens and estrogen and in
• Headache is the most frequent symptom in the control of androgen production
children (75%) • PCOS can result from abnormal function of
• Sweating in two-thirds of patients the hypothalamic–pituitary–ovarian (HPO)
• Nausea and vomiting in half of patients axis
• Hypertension
• Palpitation with or without tachycardia Clinical presentation
• Weakness or exhaustion • Menstrual dysfunction due to anovulation
• Chest pain • Hirsutism
• Dyspnea • Infertility
• Epigastric pain • Obesity
• Tremor • Metabolic syndrome
• Nervousness or anxiety • DM
• Numbness or paresthesia • Obstructive sleep apnea
• Blurred vision • Virilizing signs
• Acanthosis nigricans
Diagnosis • Hypertension
• High blood pressure or recurrent hot flushes
that are indicative of blood pressure peaks Diagnosis
• An adrenal mass • FSH levels are within the reference range or
• Family history of MEN type 2 (MEN-2) or low
von Hippel–Lindau disease • LH levels are elevated for Tanner stage, sex,
• Measurement of urinary catecholamines and and age
their metabolites in a 24-h specimen • The LH to FSH ratio is usually greater than 2–3
–– Homovanillic acid (HVA) • Elevated testosterone (or free testosterone)
–– Vanillylmandelic acid (VMA) level
–– Epinephrine • Recommended tests:
–– Norepinephrine –– TSH and free thyroxine
• Abdominal ultrasound may detect large adre- –– Serum prolactin level
nal tumor –– Total and free testosterone
• CT scan of adrenal gland –– Serum hCG level
–– Glucose level
Management –– Insulin level
• Treat with surgical removal and pretreat with –– Lipid panel
alpha-blockade –– 17-hydroxyprogesterone level (to exclude
• During a hypertensive crisis, immediately late onset CAH)
institute alpha-blockade with phenoxy- – – Karyotype usually excludes mosaic Turner
benzamine as a cause of primary amenorrhea
452 A. Morsi
• Ovarian ultrasonography • Testosterone is further converted into dihy-

–– Enlarged ovaries and cysts may or may not drotestosterone (DHT) by the action of
be present 5-alpha-reductase enzyme
• DHT is essential for complete masculiniza-
Management tion of the external genitalia
• Diet and exercise are considered first-line • Both testosterone and DHT bind to the andro-
treatment gen receptors to exert their effects; however,
• Oral contraceptive to induce regular menses DHT has a higher affinity to the androgen
• Metformin for insulin resistance receptor
• The Sertoli cells produce anti-Müllerian hor-
mone (AMH), which leads to regression of
DISORDERS OF SEXUAL the Müllerian structures
DEVELOPMENT (DSD) • The result is normal testicular development
with normal male-appearing external
Background genitalia
• Congenital conditions in which the genetics
(chromosomes), gonads, or genitals (ana- In 46 XX females
tomic sex) are atypical • In the absence of SRY, the bipotential gonad
• Current classification is based on genetics develops into an ovary. This also requires
and does not use the phenotype, as in the past. interaction of multiple autosomal genes, and
Terms such as “hermaphrodite,” “pseudoher- the notion that ovarian development is pas-
maphrodite,” or “sex errors of body” are no sive is no longer accepted
longer acceptable • In the absence of AMH, the Müllerian struc-
• The embryonic mesoderm develops the geni- tures also under control of autosomal genes
tal ridge and primitive kidney. The genital will develop into the uterus, fallopian tubes,
ridge then develops into the bipotential gonad and upper third of the vagina
• The most common cause of atypical genitalia • In the absence of androgens, the external gen-
is CAH due to 21-hydroxylase deficiency italia will develop into the normal female
leading to a virilized female phenotype phenotype
• The screening laboratory level for 21-hydrox-
ylase deficiency is 17-hydroxyprogesterone, Classification of DSD is quite complex and the
which will be markedly elevated and is following is a suggested classification
screened for on the newborn screen 46 XY DSD
• Disorders of testicular development
In 46 XY males –– Complete gonadal dysgenesis (Swyer
• The presence of SRY (sex-determining region syndrome)
on the Y chromosome) in addition to other –– Partial gonadal dysgenesis
autosomal genes will lead the bipotential • Disorders of androgen synthesis or action
gonad to differentiate in testis –– LH receptor defects → Leydig cell hypo-
• The Leydig cells in the testes produce testoster- plasia/aplasia
one, which will lead to the development of the –– Steroidogenic pathway defects: e.g.,
Wolffian structures, including epididymis, vas 17-hydroxysteroid dehydrogenase defi
deferens, seminal vesicles, and ejaculatory ducts ciency, steroidogenic acute regulatory
protein (StAR) deficiency, and 5-alpha- 5. Imaging: Abdominal/pelvic ultrasound to

reductase deficiency look for uterus, ovaries/testes (gonads)
–– Androgen receptor defects: Complete and
partial androgen insensitivity syndromes
• Disorders of AMH and its receptor, e.g., per- Congenital Adrenal Hyperplasia
sistent Müllerian duct syndrome (CAH)
46 XX DSD Background
• Disorders of ovarian development • The term encompasses a group of autoso-
• Disorders of androgen excess mal recessive disorders, each of which
–– 21-hydroxylase deficiency, 11-hydroxylase involves the deficiency of an enzyme
deficiency, aromatase deficiency, maternal involved in the synthesis of cortisol, aldo-
exogenous exposure to androgens sterone, or both
• Others, e.g., vaginal atresia
Causes
Sex chromosome DSD • The most common form of CAH is due to
• 45 XO (Turner syndrome) mutations or deletions of CYP21A, resulting
• 47 XXY (Klinefelter syndrome) in 21-hydroxylase deficiency
• Mixed gonadal dysgenesis syndrome (45 • 17-hydroxylase deficiency
X/46 XY) • 11-beta-hydroxylase deficiency
• Ovotesticular DSD (46 XX/46 XY) • 3-beta-hydroxysteroid deficiency
Clinical approach to a child with ambiguous Clinical presentation in females

genitalia • Severe form of CAH
1. Refer to newborn as “infant” without assign- –– Ambiguous genitalia at birth due to excess
ing a gender adrenal androgen production in utero
2. Consult endocrinology, psychology, urology, • Mild forms of 21-hydroxylase deficiency
genetics, and social services (simple virilizing adrenal hyperplasia)
3. History and physical exam with careful
–– Usually females are identified later in
description of genitalia childhood
(a) Is the newborn a genetic 46 XX female –– Precocious pubic hair
exposed to excess androgens (virilized –– Clitoromegaly
female)? –– Accelerated growth and skeletal matura-
(b) Is the newborn a genetic 46 XY male with tion due to excess postnatal exposure to
underproduction of androgens or adrenal androgens may occur
decreased action (undervirilized male)? • Milder deficiencies of 21-hydroxylase or
(c) Is a gonad palpable? In almost all cases, 3-beta-hydroxysteroid dehydrogenase activ-
palpable gonads are testes ity (nonclassic adrenal hyperplasia)
4. Laboratory evaluation –– May present in adolescence or adulthood
(a) Karyotype –– Oligomenorrhea
(b) First 24 h of life: Testosterone, DHT, LH, –– Hirsutism and/or infertility
FSH, AMH –– This is termed nonclassic adrenal
(c)
After 48 h of life: Electrolytes, hyperplasia
17-hydroxyprogesterone, PRA (plasma • Females with 17-hydroxylase deficiency
renin activity) –– Phenotypically female
454 A. Morsi
–– Do not develop breasts or menstruate in –– Hypokalemia

adolescence because of inadequate • Karyotype
estradiol –– It is essential in the evaluation of an infant
–– May present with hypertension with ambiguous genitalia to establish the
patient’s chromosomal sex
Clinical presentation in males
• 21-hydroxylase deficiency Management
–– Generally, not identified in the neonatal • Stabilization of patient with IV fluids if pre-
period because the genitalia are normal senting in shock or dehydration
• Severe form of 21-hydroxylase deficiency in • IV dextrose if hypoglycemic
males (classic salt-wasting congenital adrenal • IV hydrocortisone (50–100 mg/m2 or 1–2 mg/
hyperplasia) kg initial dose if signs of adrenal insuffi-
–– Usually results in salt wasting at age ciency, e.g., hypotension)
1–4 weeks • Followed by 50–100 mg/m2/day IV divided
–– Failure to thrive every 6 h
–– Recurrent vomiting • Long-term treatment
–– Dehydration –– Hydrocortisone oral
–– Hypotension –– Fludrocortisone (0.05–0.2 mg/day PO) to
–– Hyponatremia patients with mineralocorticoid
–– Hyperkalemia deficiency
–– Shock –– Oral NaCl (2–5 g/day) to infants with salt-
• Mild form of 21-hydroxylase deficiency wasting form
(simple virilizing adrenal hyperplasia)
–– May present later in childhood Remember
–– Early development of pubic hair • 11-Hydroxylase deficiency
–– Phallic enlargement –– Non-salt wasting; hypertension is the most
–– Accelerated linear growth and advance- presenting symptom, virilization can cause
ment of skeletal maturation very large clitoris mistaken for penis
• In male infants, CAH may be misdiagnosed • 17-Hydroxylase deficiency
as pyloric stenosis –– Same as 11-hydroxylase deficiency with
• Hypertension: Associated with two forms hypertension but no sex hormone or viril-
–– 11-hydroxylase deficiency ization in females, very rare
–– 17-hydroxylase deficiency • 3β-Hydroxysteroid dehydrogenase deficiency
–– Can be confused with 21-hydroxylase and
Diagnosis 11-B with late-onset and salt-wasting forms
• High serum concentration of 17-hydroxypro-
gesterone (usually > 1000 ng/dL)
• Salt-wasting forms Denys–Drash Syndrome
–– Low serum aldosterone concentrations
–– Hyponatremia Background
–– Hyperkalemia • Occurs in 46, XY individual
–– Elevated PRA • Complete Müllerian ducts usually found in
• Hypertensive forms of adrenal hyperplasia these patients
(i.e., 11-beta-hydroxylase deficiency and
17-alpha-hydroxylase deficiency)
• Nephropathy
–– Suppressed PRA
• Renal failure usually by 3 years of age –– Enlargement of penis and scrotum

• Ambiguous genitalia –– Sperm formation
• Wilms tumor • Normal adult height
wyer Syndrome (XY Pure Gonadal

S ndrogen Insensitivity Syndrome
A
Dysgenesis) (AIS)
• Most patients have mutation in SRY gene • X-linked disorder
• Y chromosome is cytogenetically normal • Due to defect in androgen receptor gene
• The gonads are undifferentiated streaks • All infants are 46, XY
• All infants have testes and normal testoster-
Clinical presentation one levels
• Complete female phenotype at birth
• Presence of vagina and fallopian tubes Clinical presentation
• At puberty, no breast development and no • Infant is phenotypically female at birth
menstruation • Most infants raised as female and identify
with female gender
Prognosis • External genitalia are female and the vagina
• Development of gonadoblastoma is the high- ends in a blind pouch
est risk • No uterus
• Fallopian tubes may or may not be present
Management • Testes are usually intra-abdominal
• Gonads must be removed as soon as the diag- • At puberty, breasts develop normally
nosis is made • No menses
• Sexual hair does not appear
• Normal male adult height
5-Alpha-Reductase Deficiency • Testosterone may be normal or high
Background
Summary of DSD (Table 12.6)
• Due to defect in androgen action on external
genitalia
• This causes ambiguity of external genitalia DIABETES MELLITUS
• Peripheral action of testosterone is normal
Type 1 Diabetes Mellitus
• Newborn with small penis, bifid scrotum, Background
urogenital sinus, and a blind vaginal pouch • Type 1 DM is a chronic illness characterized
• Testes are in inguinal canal by the body’s inability to produce insulin due
• Most infants are raised as female and changed to the autoimmune destruction of the beta
to male at the time of puberty cells in the pancreas
• At puberty • Most pediatric patients with DM have type 1
–– Virilization occurs and a lifetime dependence on exogenous
–– Male hair distribution insulin
456 A. Morsi
Table 12.6 Keywords of common causes of disorders of –– Fasting plasma glucose (FPG) level
sexual development ≥ 126 mg/dL (7.0 mmol/L), or
Description of DSD Diagnosis –– 2-hour plasma glucose level ≥ 200 mg/dL
XX newborn Congenital adrenal (11.1 mmol/L) during a 75-g oral glucose
Virilization of external hyperplasia (CAH)
tolerance test (OGTT), or
genitalia
Ultrasound: normal –– Random plasma glucose ≥ 200 mg/dL
Müllerian structures (11.1 mmol/L) in a patient with classic
17 hydroxyprogesterone is symptoms of hyperglycemia or hypergly-
very high cemic crisis
XY female phenotype Androgen insensitivity
(raised female) syndrome (AIS)
–– HbA1C≥ 6.5%
Breast, no menses, no • Glycated hemoglobin
sexual hair –– Measurement of HbA1c levels is the best
Blind vaginal pouch (MIS method for medium- to long-term diabetic
is normal) control monitoring
Undescended testes
Elevated testosterone level –– New target for HbA1C in children is < 7.5%
→ estradiol → breast –– Benefits of tight glycemic control include
XY female phenotype Swyer syndrome (XY pure not only continued reductions in the rates
(raised female) gonadal dysgenesis) of microvascular complications but also
No breast, no menses, no significant differences in cardiovascular
sexual hair
events and overall mortality
Has vagina, uterus, and
fallopian tube • Positive autoimmune markers (glutamic acid
Streak gonads decarboxylase [GAD], insulin islet cell, and
Low testosterone Zn transporter antibodies)
XY female phenotype at 5-Alpha-reductase deficiency • Blood glucose tests
birth (no dihydrotestosterone)
–– Capillary blood samples, reagent sticks,
No breast, no menses
Develop sexual hair, and blood glucose meters are the usual
enlarging penis methods for monitoring day-to-day diabe-
No internal Müllerian tes control
structures
Testes are inguinal canal Management
XY normal male Persistent Müllerian duct
phenotype syndrome
• Insulin therapy
Inguinal hernia, –– All children with type 1 DM require insu-
undescended testes lin therapy
Mullerian structure found –– Most require two or more injections of
incidentally insulin daily, with doses adjusted on the
basis of self-monitoring of blood glucose
Clinical presentation levels
• Hyperglycemia –– Insulin replacement is accomplished by
• Glycosuria giving basal insulin and a preprandial (pre-
• Polydipsia meal) insulin
• Unexplained weight loss –– The basal insulin is either long-acting
• Nonspecific malaise (glargine or detemir) or intermediate-act-
• Symptoms of ketoacidosis ing (neutral pH protamine [NPH]). The
preprandial insulin is either rapid-acting
Diagnosis
(lispro, aspart, or glulisine) or short-acting
• Diagnostic criteria by the American Diabetes
(regular)
Association (ADA) include the following:
• Diet and activity • Positive screening: High tTG IgA titer

–– The aim of dietary management is to bal- • Positive screening management: Refer to gas-
ance the child’s food intake with insulin troenterologist to confirm diagnosis before
dose and activity and to keep blood glucose starting a gluten-free diet
concentrations as close as possible to refer-
ence ranges, avoiding extremes of hyper- Addison disease
glycemia and hypoglycemia • Rare association with type 1 DM, so no uni-
–– Carbohydrates should provide 50–55% of versal screening warranted
daily energy intake; no more than 10% of • Suspect if patient is having unexplained
carbohydrates should be from sucrose or hypoglycemia or decreased insulin require-
other refined carbohydrates ments, losing weight, increased pigmenta-
–– Fat should provide 30–35% of daily energy tion of the skin and gingival mucosa, salt
intake craving, weakness, and postural hypotension
–– Protein should provide 10–15% of daily
energy intake Important to know: Consider the diagnosis of
• Exercise autoimmune polyglandular syndrome type II in
–– An important aspect of diabetes patients with type 1 DM, autoimmune thyroiditis,
management and autoimmune adrenal insufficiency
–– Has real benefits for a child with diabetes
Screening for associated comorbidities/
–– Patients should be encouraged to exercise
complications
regularly
Dyslipidemia
Screening for associated autoimmune • Screening starts and frequency: 10 years of
conditions: age or when puberty starts, whichever comes
Thyroid screening first, and then annually
• Autoimmune thyroiditis is the most common • Risk factors: Family history of early cardio-
autoimmune disease associated with type 1 DM vascular disease (< 55 years of age)
• Screening start and frequency: At diagnosis • How to screen: Non-fasting lipid panel
and then annually • Positive screening management
–– Positive screening: Low-density lipopro-
Celiac screening tein (LDL) 100 mg/dl or above
• Celiac disease is the second most common –– Start by lifestyle change and Step II
autoimmune disease associated with type 1 American Heart Association (AHA) diet
DM –– If lifestyle not effective, a statin is war-
• Clinical picture: Classic symptoms include ranted if the child is 10 years or older
abdominal pain, diarrhea, or constipation.
Some patients present with growth failure, Retinopathy screening (dilated eye exam)
reduced insulin requirement, or hypoglyce- • Screening starts: 10 years of age or above and
mia due to erratic absorption of nutrients. DM duration of 3–5 years
Many children especially at a younger age are • How frequent: Annually if normal
completely asymptomatic
• Screening start and frequency: At diagnosis Nephropathy screening
and then annually • Screening starts: At puberty or age ≥ 10 years,
• How to screen: tTG IgA (in addition to a total whichever is earlier, once the child has had
IgA level) DM for 5 years
458 A. Morsi
• How to screen: Spot urine albumin to creati- –– Race/ethnicity: Native American, African-
nine ratio. (12–24 h urine collections did not American, Latino, Asian American, or
improve detection of albuminuria and are Pacific Islander
more burdensome) –– Maternal history of DM or gestational DM
• Positive screening management during the child’s gestation
–– Positive if ratio 30 mg/gm creatinine or • Screening should start at 10 years of age or
above at the start of puberty if it occurs at a
–– If persistently positive (2 out of 3 sam- younger age
ples): Treatment with an ACE inhibitor is • Screening should be repeated every 3 years
warranted • Diagnosis is established in the presence of
one of the following criteria:
–– A random plasma glucose concentration of
Type 2 Diabetes Mellitus 200 mg/dL or greater in association with
classic symptoms of hyperglycemia (poly-
Background uria, polydipsia, or nocturia) or a hypergly-
• Characterized by cemic crisis
–– Hyperglycemia –– FPG value of 126 mg/dL or greater
• Insulin resistance –– 2-hour plasma glucose value of 200 mg/dL
–– Family history of type 2 DM in first- or or greater during an OGTT
second-degree relative –– HbA1c levels equal or greater than 6.5%
• Obesity strongly associated with type 2 in • Other laboratory results that are suggestive of
children and adolescents type 2 DM but not needed for diagnosis are as
follows:
–– Elevated fasting C-peptide level
• Slow and insidious onset
–– Elevated fasting insulin level
• Signs of insulin resistance, e.g., acanthosis
–– Absence of autoimmune markers (see Type
nigricans
1 DM)
• Strong family history of type 2 DM: Familial
lifestyle risk factors leading to obesity may Management
be present; family history of cardiovascular • Diabetes education and lifestyle changes
disease or metabolic syndrome (diet, exercise, and weight control)
• PCOS • The only pharmacologic therapy that is FDA-
• Hypertension approved in children is metformin and
• Retinopathy insulin
• Metformin is the initial drug of choice for
Screening and diagnosis
treatment of type 2 DM in metabolically sta-
• Screening for type 2 DM should be consid-
ble patients (A1C < 8.5% and asymptomatic)
ered when a patient is overweight or obese
if renal functions are normal
and has one or more of the following:
• Children with marked hyperglycemia (blood
–– Family history of type 2 DM in first- or
glucose ≥ 250 mg/dL, A1C ≥ 8.5%) without
second-degree relative
acidosis at diagnosis who are symptomatic
–– Signs of insulin resistance or conditions
with polyuria, polydipsia, nocturia, and/or
associated with insulin resistance (e.g.,
weight loss should be treated initially with
acanthosis nigricans, hypertension, dyslip-
basal insulin while metformin is initiated and
idemia, PCOS and SGA birth weight)
titrated
• In patients with ketosis/ketoacidosis, treat- –– Start by lifestyle change and Step 2 AHA
ment with subcutaneous or IV insulin should diet
be initiated to rapidly correct the hyperglyce- –– If lifestyle is not effective after 6 months, a
mia and metabolic derangement. statin is warranted with a goal of LDL
• Once ketosis/ketoacidosis is resolved, met- below 100 mg/dl
formin should be initiated while subcutane-
ous insulin therapy is continued Retinopathy screening (dilated eye exam)
• Screening starts and frequency: At diagnosis
Management of Comorbidities/ and then annually
Complications
Neuropathy screening:
Nephropathy screening • Screening starts and frequency: At diagnosis
• Screening starts: At diagnosis and then annu- and then annually
ally if normal • How to screen: Examination should include
• How to screen: Spot urine albumin to creati- inspection, assessment of foot pulses, pin-
nine ratio. (12–24 h urine collections did not prick, and 10-g monofilament sensation tests;
improve detection of albuminuria and are testing of vibration sensation using a 128-Hz
more burdensome) tuning fork, and ankle reflexes
• Positive screening management
–– Positive if ratio is 30 mg/gm creatinine or Nonalcoholic fatty liver disease
above • Screening starts and frequency: At diagnosis
–– If persistently positive (2 out of 3 samples): and then annually
Treatment with an ACE inhibitor is • How to screen: Aspartate aminotransferase
warranted (AST) and alanine aminotransferase (ALT)
levels
Hypertension
• Positive screening management: Lifestyle
• Increases risk for cardiovascular and renal
modifications and referral to
disease
gastroenterologist
• Blood pressure should be measured accu-
rately and reviewed at each visit
• Both systolic and diastolic blood pressures PCOS
should be below the 90th percentile for age, • Screening is indicated if showing signs/symp-
gender, and height toms of PCOS
• Pharmacological therapy with an ACE inhibi- • Metformin may be beneficial in the treatment
tor is indicated if hypertension persists after of girls with type 2 DM and PCOS. Oral con-
6 months of lifestyle modifications traceptives can also be used
Dyslipidemia Obstructive sleep apnea

• Screening starts and frequency: At diagnosis • Start screening at diagnosis and at each
and then annually visit
• How to screen: Non-fasting lipid panel • Refer to a pediatric sleep specialist for
• Positive screening management evaluation and a sleep study if showing
–– Positive screening: LDL 100 mg/dl or above, positive symptoms (snoring, insufficient
or high-density lipoprotein (HDL) 35 mg/dL or disrupted sleep, circadian rhythm
or lower, triglycerides 150 mg/dL or above dysregulation)
460 A. Morsi
Depression Management
• The prevalence of clinically significant symp- • Hydration is the most important first step
toms of depression were reported to be at –– IV fluid replacement is begun as soon as
14.8% in the TODAY cohort of youth with the diagnosis of DKA is established
type 2 DM – – Initial fluid resuscitation begins with
• Screen using age-appropriate tools and refer 10 mL/kg of isotonic fluid, 0.9% saline
to specialty care when indicated administered over 1 h
–– After the initial fluid resuscitation, the
Summary remainder of the fluid deficit is replaced
• Treatment goals include improvement of gly- evenly over 48 h (most patients are 6%
cemia (HbA1c) levels (< 7%), dyslipidemia dehydrated)
(LDL level < 100 mg/dL, triglyceride –– Maintenance fluid requirements are
< 150 mg/dL, HDL level > 35 mg/Dl), and added to this deficit replacement to pro-
hypertension (blood pressure < 90th percen- vide the total fluid requirements, which
tile for age, sex, and height) rarely exceed 1.5 times the usual daily
fluid requirement
–– The 0.9 saline with added 30–40 mEq/L of
Diabetes Ketoacidosis (See Chap. 7 potassium is continued as the hydration
also “Emergency Medicine”) fluid until the blood glucose value declines
to less than 300 mg/dL
Precipitating factors that could lead to the onset –– Replacement fluid should be changed to
of DKA D5 0.45% with added potassium when
• Infection glucose value declines to less than
• Insulin omission 300 mg/dL
• Insulin pump failure –– If the blood glucose concentration declines
• Failure to match insulin dosing to metabolic below 150 mg/dL (8.3 mmol/L), dextrose
requirements during illness or stress content may need to be increased to 10%
or even 12.5%
Diagnosis
• Blood glucose level greater than 200 mg/dL Insulin
• Presence of serum/urine ketones • Time of insulin initiation is controversial
• Venous pH < 7.30 or a bicarbonate level less • Insulin is administered as a continuous IV
than 15 mmol/L infusion of regular insulin at a rate of 0.05–
0.1 units/kg/h
Severity of DKA can be classified according to • Bolus of insulin should not be given at the
the severity of the acidosis start of therapy
• Mild • If IV administration of insulin is not possible,
–– Venous pH 7.21–7.30 short- or rapid-acting insulin injected subcu-
–– Bicarbonate (mmol/L) 11–15 taneously every 2 h can be effective
• Moderate
–– Venous pH 7.11–7.20 Resolution of the acidosis in DKA
–– Bicarbonate (mmol/L) 6–10 • Acidosis (pH > 7.3)
• Severe • Bicarbonate > 15 mEq/L
–– Venous pH < 7.10 • IV insulin therapy should continue as long as
–– Bicarbonate (mmol/L) < 5 the patient is still acidotic
• Decrease IV insulin rate if there is persistent erate to large urine ketone levels (or blood
hypoglycemia despite maximum dextrose ketone levels greater than 1.5 mmol/L)
administration • Inappropriately rapid breathing
• Subcutaneous insulin must be started before • Altered mental status
discontinuation of IV insulin when acidosis is • Inability to perform sick day rules
resolved
Monitoring aturity-Onset Diabetes of Youth

M
• Vital signs (MODY)
• Mental status and neurologic evaluation
• Serum glucose, electrolytes including serum Background
phosphorus (including blood urea nitrogen • MODY is the most common form of mono-
and creatinine), and pH and urine ketones genic diabetes
should be measured at presentation • The genes involved control the pancreatic
• Serum glucose and pH should be measured beta cell development, function, and regula-
hourly tion, hence leading to defects in glucose sens-
• Serum electrolytes and urine ketones assessed ing and insulin secretion
every 2–3 h • Onset is usually before 25 years of age
• If phosphate is administered, serum calcium • Inherited in an autosomal dominant pattern
concentrations must be monitored
Types
• MODY 1–MODY 6 are the most common
Outpatient Management of Sick identified gene mutations, with MODY 3
Days in Patient with Diabetes (hepatocyte nuclear factor-1 alpha = HNF1A)
Mellitus being the most common, representing about
50% of monogenic diabetes cases
Management steps
• Check blood glucose level every 2–3 h until Diagnosis
feeling well. Urine ketones should be checked • Suspect in individuals with the following
frequently characteristics:
• It is important to teach families that adjust- –– Diabetes diagnosis before 25 years of
ments in the insulin doses are necessary dur- age
ing intercurrent illness, but a complete – – Autosomal dominant pattern of inheritance
cessation of all insulin replacement will of diabetes (> 2 generations affected)
quickly lead to diabetic ketoacidosis – – Nonobese (usually)
• Encourage fluid intake. Ideally, give 1 oz –– Negative islet antibodies (markers of type
(30 mL) per year of age per hour in small, 1 DM)
frequent sips • Genetic testing is readily available
–– If glucose level is ≥ 200 mg/dL, sugar-free
Treatment
fluids should be given
• MODY 4–6 are treated with insulin
–– If glucose level is < 200 mg/dL, sugar-con-
• MODY 1 and MODY 3 are treated with
taining fluids should be included
sulfonylureas
Factors warranting medical evaluation • MODY 2 is treated with diet and exercise but
• Persistent vomiting (e.g., vomiting more than may require insulin during illness or
twice after starting sick day rules) with mod- pregnancy
462 A. Morsi
Obesity • Plus at least two of the following four clinical

risk factors:
Background –– BP ≥ 130 mmHg systolic or ≥ 85 mmHg
• The most commonly used measure is body diastolic or drug treatment for
mass index (BMI) hypertension
• BMI is defined as kilograms (kg) of body –– HDL < 40 mg/dL in men or < 50 mg/dL in
weight per height in square meters (m2) women or treatment for lipid
• Overweight: BMI between 85th and 94th abnormalities
percentile –– Triglyceride level ≥ 150 mg/dL
• Obesity: BMI at or above 95th percentile –– FPG level ≥ 100 mg/dL or previously diag-
nosed type 2 DM
Causes
• Idiopathic or familial obesity Obesity-related conditions
–– Poorly understood • Depression and isolation are the most com-
–– Most common cause of childhood obesity mon complications of obesity in children and
• Hormonal, e.g., adolescents
–– Hypothyroidism • Liver
–– GHD –– Fatty liver infiltration (nonalcoholic steato-
–– Hypogonadism hepatitis [NASH]) 25–83%
–– Cushing syndrome –– Cholelithiasis (50% are obese)
–– PCOS • Pulmonary
• Syndromic, e.g., –– Obstructive sleep apnea
–– Down syndrome –– Metabolic alkalosis and respiratory
◦◦ Hypotonia acidosis
–– Prader–Willi syndrome –– Hypoventilation
◦◦ Hypotonia, hypogonadism, hyperpha- –– Pulmonary hypertension
gia, small hands and feet –– Right-sided heart failure
–– Albright hereditary osteodystrophy –– Obesity hypoventilation syndrome
◦◦ Short stature and skeletal defect –– Asthma
–– Bardet–Biedl syndrome –– Renal
◦◦ Retinal dystrophy, renal abnormalities, • Nocturnal enuresis
mental retardation –– Related to obstructive sleep apnea and
–– Fragile X syndrome excess secretion of atrial natriuretic pep-
◦◦ Macro-orchidism and large ears tide (ANP)
• Genetic, e.g., • Cardiovascular
–– Melanocortin 4 receptor deficiency –– Hypertension (60% are obese)
(MC4R) –– Systolic blood pressure > 95% for age, sex,
–– Congenital leptin deficiency and height
–– Leptin receptor defect –– Dyslipidemia
–– HDL < 40 mg/dL
Definition of Pediatric Metabolic Syndrome –– LDL > 130 mg/dL
(International Diabetes Federation Criteria) –– Triglyceride > 150 mg/dL
• Central obesity (required feature) > 90th per- –– Total cholesterol > 200 mg/dL
centile for age, gender, and ethnicity with • Musculoskeletal complications
waist circumference ≥ 94 cm in men or –– Slipped capital femoral epiphysis (30–50%
≥ 80 cm in women are obese)
–– Blount disease or tibia vara (70% are obese) PEARLS AND PITFALLS

–– Severe leg bowing of tibia, knee pain, and
limp • Assessing growth velocity (linear growth) is
–– Osteoporosis as important as assessing height percentiles
–– Back pain when assessing short stature in children.
–– Joint pain • Bone age radiograph is a useful tool that can
• Acanthosis nigricans and insulin resistance be used to differentiate between different
(Fig. 12.10) causes of short stature or poor linear growth.
–– Not a criteria of metabolic syndrome • Growth hormone is not the major determinant
diagnosis of growth in the first 4–6 months of life.
–– High concentration of insulin in obese • Signs of congenital hypopituitarism include
patients may exert potent proliferative hypoglycemia and micropenis (in boys).
effects via high-affinity binding to IGF-1, • Congenital hypothyroidism is the most com-
which stimulate epidermal keratinocyte mon cause of preventable intellectual disabil-
and dermal fibroblast proliferation ity. Treatment with thyroid hormone
replacement should not be delayed.
Management • Children presenting with normal variants of
• Multidisciplinary approach puberty (premature thelarche, premature
• Weight reduction adrenarche) need to be followed more closely
• Diet and exercise than regular well-child visits, as they may be
• Management of obesity-related conditions presentations for true precocious puberty in
• Treatment of the cause if applicable 18–20% of cases.
• Klinefelter syndrome is the most common
cause of hypergonadotropic hypogonadism
with a prevalence of 1 in 700 males.
• Always consider the diagnosis of Turner syn-
drome when evaluating a girl with short stat-
ure, as it may be the only presenting sign.
• Be aware of the different potencies of oral ste-
roids commonly used. Hydrocortisone is equiv-
alent to our endogenous cortisol (×1), prednisone
(4 × hydrocortisone equivalent), dexametha-
sone (40 × hydrocortisone equivalent).
• Inhaled corticosteroids are associated with
endocrine effects, including hyperglycemia,
iatrogenic adrenal insufficiency, and linear
growth effects.
• When interpreting an endocrine laboratory
result, it is important to use pediatric refer-
ence ranges. Also, a normal value might not
always be considered normal in certain sce-
narios. For example, a low normal TSH level
Fig. 12.10 A 17-year-old female with obesity and metabolic with a low normal thyroid hormone level is
syndrome. Weight 180 lbs, height 60 in., BMI 35th percentile,
blood pressure 140/90 mmHg. She has poorly defined, vel-
suspicious of central hypothyroidism despite
vety hyperpigmentation of the skin around the neck both values being in the normal range.
464 A. Morsi
Acknowledgment The author gratefully acknowledges the contribu- Guidelines for growth hormone and insulin-
tions of Kuk-Wha Lee, MD, PhD, Division of Endocrinology,
Department of Pediatrics, David Geffen School of Medicine at UCLA, like growth factor-I treatment in children and
Los Angeles, California, USA, to the 1st edition of this chapter, many adolescents: growth hormone deficiency, idio-
of which have been incorporated into this edition as well.
pathic short stature, and primary insulin-like
growth factor-I deficiency. Horm Res Paediatr.
2016;86(6):361–97.
Suggested Reading Lee PA, Houk CP, Ahmed SF, Hughes IA,
International Consensus Conference on Intersex
American Diabetes Association. 13. Children organized by the Lawson Wilkins Pediatric
and adolescents: standards of medical care in Endocrine Society and the European Society
diabetes-2019. Diabetes Care. 2019;42(Suppl for Paediatric Endocrinology. Consensus state-
1):S148–64. Review. ment on management of intersex disorders.
Anderson BJ, Edelstein S, Abramson NW, Katz International Consensus Conference on Intersex.
LE, Yasuda PM, Lavietes SJ, et al. Depressive Pediatrics. 2006;118(2):e488–500.
symptoms and quality of life in adolescents with Speiser PW, Arlt W, Auchus RJ, Baskin LS,
type 2 diabetes: baseline data from the TODAY Conway GS, Merke DP, et al. Congenital adre-
study. Diabetes Care. 2011;34(10):2205–7. nal hyperplasia due to steroid 21-hydroxylase
Carel JC, Eugster EA, Rogol A, Ghizzoni L, deficiency: An Endocrine Society Clinical
Palmert MR, ESPE- LWPES GnRH Analogs Practice Guideline. J Clin Endocrinol Metab.
Consensus Conference Group, et al. Consensus 2018;103(11):4043–88.
statement on the use of gonadotropin-releas- Thornton PS, Stanley CA, De Leon DD, Harris D,
ing hormone analogs in children. Pediatrics. Haymond MW, Hussain K, Pediatric Endocrine
2009;123(4):e752–62. Review. Society, et al. Recommendations from the
Grimberg A, DiVall SA, Polychronakos C, Pediatric Endocrine Society for evaluation
Allen DB, Cohen LE, Quintos JB, Drug and and management of persistent hypoglycemia
Therapeutics Committee and Ethics Committee in neonates, infants, and children. J Pediatr.
of the Pediatric Endocrine Society, et al. 2015;167(2):238–45.
Orthopedics
13
Amr Abdelgawad and Marwa Abdou
GENERAL CONDITIONS –– Developmental dysplasia of the hip (wad-

dling gait when bilateral)
Limping Child –– Chronic SCFE
–– Chronic Legg–Calve–Perthes disease
Background –– Muscular dystrophy (high creatine kinase
• Limping is a common complaint in pediat- [CK]), and bilateral affection)
rics, a condition that may be due to pain, • Circumduction (swing around and to the side)
weakness, or musculoskeletal deformities –– Leg-length discrepancy (also toe walking
• Growing pains usually do not cause limping or steppage gait)
–– Cerebral palsy with stiff gait
Causes • Toe walking
• Antalgic gait (limping because of pain) –– Idiopathic toe walking
–– Osteomyelitis, diskitis, transient synovitis, –– Leg-length discrepancy
septic arthritis, toddler fractures, juvenile –– Cerebral palsy (hypertonia of the
idiopathic arthritis, pedal puncture wound gastrocnemius)
–– Slipped capital femoral epiphysis (SCFE) –– Muscular dystrophy (high CK) (the ankle
–– Tumors: Ewing sarcoma, osteoid osteoma, dorsiflexors affected more than the gas-
acute leukemia, neuroblastoma trocnemius muscle)
–– Legg–Calve–Perthes disease
–– Overuse syndrome (patella–femoral over- Diagnosis
load), stress fractures of the foot • Based on detailed history and thorough phys-
–– Osteochondritis (Osgood–Schlatter dis- ical examination
ease, Sever disease) • Narrow the differential diagnosis by classify-
–– Osteochondritis dissecans (of the distal ing the limp according to:
femur or the talus) –– Gait pattern
• Trendelenburg gait (weak hip abductors cause –– Chronicity of limping
shift of body weight to the weak side) –– Presence or absence of pain
–– Age of the child
–– Anatomic region involved
A. Abdelgawad (*)
Department of Orthopaedic Surgery and Rehabilitation, Texas Tech
M. Abdou
Department of Pediatrics, Texas Tech University Health Sciences
Center, El Paso, TX, USA

466 A. Abdelgawad and M. Abdou
• Choice of imaging modalities and laborato- • Progressively worsening leg-length discrep-

ries is dependent on the differential diagnosis ancies that occur after trauma and infections
and the most likely cause of limp; this may or from undetermined source should be
include: referred to a pediatric orthopedics as soon as
–– Radiograph, bone scan, ultrasound, com- they are recognized
puterized tomography (CT) scan, magnetic • Shoe lifts
resonance imaging (MRI) • Limb shortening (for discrepancies between
–– Complete blood count (CBC), erythrocyte 2 and 5 cm)
sedimentation rate (ESR), C-reactive pro- • In skeletally immature children: Stopping the
tein (CRP), CK growth of the contralateral side
• Limb lengthening (usually for discrepancies
> 5 cm)
Leg-Length Discrepancy
Background rthrogryposis
A
• Up to 35% of adults have discrepancies
between 0.5 and 1.5 cm Background
• Clinically significant leg-length discrepan- • A group of syndromes associated with
cies usually have an identifiable cause decreased fetal movement that results in mul-
tiple joint contracture. The most common
Causes syndrome is amyoplasia (characterized by the
• Idiopathic leg-length discrepancy four limbs being involved and by replacement
• Affection of the growth plate by trauma, of skeletal muscle by dense fibrous tissue).
infection, or tumors • The incidence is 1 in 3000.
• Congenital conditions, e.g., fibular hemime-
lia, hemihypertrophy Clinical Presentation
• Unilateral hip dislocation • History of decreased fetal movement during
pregnancy
Clinical presentation • Loss of skin creases across joints
• Abnormal gait • Severe muscle atrophy and a decrease in sub-
• Toe walking cutaneous fat
• Compensatory scoliosis • Restricted range of motion (ROM)
• Back or hip pain • Shoulders are internally rotated, elbows are
extended, and fingers are thin and tapered
Diagnosis • Scoliosis
• History and physical exam • Knee contractures
–– Measure the leg length using a tape mea- • Clubfoot is the most common foot
sure from the midline (umbilicus to the tip deformity
of the medial malleolus)
• Radiograph: A weight-bearing anteroposte- Diagnosis
rior (AP) radiograph of both lower • Diagnosis is based on history and physical
extremities examination
• Prenatal ultrasound may suggest the diagnosis
Management due to decreased fetal movement, microgna-
• Observation, e.g., if the discrepancy is less thia, joint contractures, and oligohydramnios
than 2 cm, nonprogressive with no symptoms
13 Orthopedics 467
Management is often autosomal dominant or occasionally

• Multidisciplinary team approach: Pediatric random, while syndromic polydactyly is
orthopedic surgeon, geneticist, occupational commonly autosomal recessive
and physical therapists
• Patient-specific equipment to help the patient Diagnosis
perform his/her daily activities (e.g., specific • About 15–20% of children born with poly-
utensils, patient-specific walker) dactyly have other congenital anomalies, usu-
• Surgical treatment for joint contracture ally as a part of a defined syndrome (more
common among preaxial polydactyly). Hand
postaxial polydactyly is less often associated
Polydactyly of the Hand with other congenital anomalies.
Background Treatment
• Definition: Presence of an extra digit (or • Unless there is a clear family history of iso-
duplication) lated polydactyly, any newborn with polydac-
• The most common congenital digital anom- tyly should be investigated for the presence of
aly of the hand and foot associated anomalies.
• A common form is an extra thumb (radial –– Thorough medical examination and genetic
polydactyly or preaxial polydactyly), more workup in these patients are
common among Caucasians (Fig. 13.1) recommended
• Ulnar (postaxial) polydactyly is usually a • Postaxial polydactyly in black children does
small, poorly formed, extra digit attached by not need further workup
a thin stalk of soft tissue (Fig. 13.2). More • Surgical removal: For small rudimentary
common among African Americans ulnar polydactyly attached by a thin stalk, the
• It may appear in isolation or in association
with other birth defects. Isolated polydactyly
Fig. 13.1 Thumb polydactyly. A 1-year-old boy with radial Fig. 13.2 Ulnar polydactyly. An extra small digit on the
polydactyly ulnar side of the hand attached to the hand with a stalk
base can be tied with a suture in the newborn • The most common route by which the bacte-
period, and it will fall off spontaneously. ria enter a joint is by hematogenous spread to
• For more developed extra digits, radial poly- the synovium
dactyly, or polydactyly in older children: • Most common organism in general is
Orthopedic referral for surgical excision Staphylococcus aureus
• In newborns, group B streptococcus is more
common
Viral Myositis • In sexually active adolescents, gonococcus is
the most common organism
Causes • Kingella kingae bacteria is a common cause
• Viral infections, e.g., influenza virus infection of musculoskeletal infections in young chil-
dren less than 5 years old
• Most commonly affected joints: Hip, shoul-
• Muscle weakness and tenderness
der, and knee
Diagnosis
Diagnosis
• Elevated creatinine kinase
• General signs of infection (fever, chills)
Treatment • Swelling (effusion), rigidity of the joint (very
• Supportive limited ROM), tenderness, inability to bear
weight with lower extremity joints
• Elevated markers of infection (white blood
ONE AND JOINT INFECTION/
B cell count [WBC], ESR, CRP)
• Joint aspiration (arthrocentesis/ultrasound-
INFLAMMATION guided aspiration of the joint fluid) for Gram
stain, culture, and cell count (cell count
Transient Synovitis > 50,000/mL is indication for septic
arthritis)
Background
• Nonspecific inflammation of the joint (may Treatment
be related to viral infection or trauma) • Septic arthritis is an urgent surgical condi-
tion. Urgent orthopedic consult is needed for
Diagnosis (transient synovitis of the hip joint)
urgent irrigation and debridement of the joint
• Variable clinical pictures; hip pain, limping,
inability to bear weight on the affected side, Antimicrobial management of pyogenic
or complete rigidity arthritis
• Markers of infection: Normal to mildly • If methicillin-resistant S. aureus (MRSA) is
elevated suspected, e.g., history of hospitalization,
• Low-grade fever can be seen in some cases contact with MRSA cases, and recurrent tis-
sue abscesses or positive nasal MRSA test-
Treatment
ing: Best initial IV empiric antimicrobials are
• NSAIDs, rest
–– Clindamycin
–– Vancomycin
Septic Arthritis • Methicillin-sensitive S. aureus cases:
–– IV cefazolin
Background • Cases of K. kingae:
• Bacterial inflammation of the synovium of –– Third-generation cephalosporins (e.g., cef-
the joint triaxone) are effective
13 Orthopedics 469
Table 13.1 Differentiation between septic arthritis of the Table 13.2 Difference between septic arthritis, arthritis due
hip and transient synovitis to rheumatic fever, and juvenile rheumatoid arthritis
Septic arthritis Transient synovitis Arthritis due
Fever Usually present Normal or mild to rheumatic Juvenile rheumatoid
elevation Septic arthritis fever arthritis
ESR, CRP, Usually elevated Normal or mild Acute onset Acute onset Chronic > 6 weeks
WBC elevation Staphylococcus Post- Autoimmune disease
Inability to Common Rare aureus most streptococcal
walk common cause infection
Aspiration Positive for Gram Negative for Gram Painful, limited Very painful Joint swelling and
stain +/− culture stain and culture range of motion and migratory limping
Cell count > 50,000/ Cell count < 50,000/ Usually one joint More than one Usually more than
ml ml (a) joint one joint
Blood May be positive Negative Urgent surgical Treatment of Anti-inflammatory
culture drainage/irrigation acute (see Chap. 15,
From Abdelgawad and Naga [3], with permission and antibiotics rheumatic “Rheumatology”)
ESR erythrocyte sedimentation rate, CRP C-reactive protein, fever
WBC white blood cell count a
Multiple joint involvement is uncommon but occurs in up to
50% of Neisseria gonorrhoeae infections
• Neonates with septic arthritis must be cov-
ered for group B streptococcal disease and A cute Hematogenous Osteomyelitis
enteric Gram-negative rods in addition to S.
aureus Background
–– For example, nafcillin with either gentami- • Acute bacterial infections of the bone (mainly
cin or cefotaxime metaphysis of long bones)
• S. aureus is the most common organism
How to differentiate between transient synovitis • Group B streptococcus and Escherichia coli
and septic arthritis of the hip joint (Table 13.1) [1] are common in neonates. Pseudomonas is
Modified Kocher Criteria common in osteomyelitis after puncture
• History of fever > 38.5C wound through tennis shoes
• Inability to bear weight on the affected limb • K. kingae is becoming an increasingly identi-
• ESR > 40 mm/h fied cause in children less than 5 years old
• WBC > 12,000 cells/mL
• CRP level of more than 20 mg/L Diagnosis
• The more criteria the child has, the more • General signs of infection (fever, chills)
likely the diagnosis of septic arthritis • Swelling, tenderness, and redness over the
affected bone
Arthritis associated with rheumatic fever • Nearby joint is mildly swollen; however,
(Table 13.2) movement of the joint is largely preserved
• Arthritis due to acute rheumatic fever is very • Elevated markers of infection (WBC, ESR,
painful and has a migratory nature (joint will CRP)
stay swollen for about 12 h, and then another • Radiographs are normal in the first 10–14 days
joint will become symptomatic while the and then show periosteal reaction
symptoms of the first joint subsides) • MRI: Very sensitive, positive early in the dis-
• Patient must meet the criteria for the diagno- ease; can show development of subperiosteal
sis of acute rheumatic fever (see Chap. 19 abscess
“Cardiology”).
• Bone scan: Positive early in the disease pro- • Mild or no fever

cess; the affected area will appear “hot” in the • Paraspinal muscle spasm
scan • Flexion of the spine compresses the anterior
• Blood culture: Positive in 50% of cases element and causes discomfort (child will
• Bone aspiration for Gram stain, culture, and refuse to pick up an object from the ground;
pathology instead, he/she will flex hips and knees, not
the back)
Treatment • Older children might have fever and abdomi-
• Osteomyelitis is a medical condition nal pain
–– Antibiotics should be given according to • Laboratory: CBC may remain normal. ESR
sensitivity studies (either blood culture or and CRP are usually elevated
bone biopsy cultures) and according to • Image-guided biopsy from the affected area
organism sensitivity prevalence in the for culture
community • Radiographs: PA and lateral radiographs of
–– Appropriate antimicrobial therapy (see the thoracolumbar spine is the first image to
treatment of septic arthritis) be ordered when the condition is suspected.
• Indication for surgical debridement (orthope- Characteristic finding often takes 2–3 weeks
dic consultation): to show these changes: narrowing of the disk
–– No improvement after 36 h of antibiotic space
administration • MRI: Most sensitive imaging study. Becomes
–– Development of subperiosteal abscess positive early in the disease process
–– Extension to nearby joint • Technetium bone scan: Hot spot in the
affected disk
iskitis and Vertebral Body

D Treatment
Osteomyelitis • Start antibiotics covering for S. aureus, then
according to culture results. Length of ther-
Background apy is 4–6 weeks.
• Diskitis is an inflammation of the interverte- • Rest, analgesic, and immobilization in spinal
bral disk usually seen in toddlers. It occurs orthosis
most commonly in the lumbar vertebrae • Surgical treatment is rarely required.
• Vertebral body osteomyelitis is an inflamma-
tion of the vertebral body; usually starts at the
vertebral end plates NECK DISORDERS
• The distinction between diskitis and vertebral
osteomyelitis is difficult, and most cases will Torticollis
have some affection of both the intervertebral
disk and the vertebral body Background
• Etiology: Hematogenous spread. S. aureus is • Clinical finding of tilting the head to one side
the most common organism isolated in combination with rotation of face to the
opposite side (Fig. 13.3)
Diagnosis • May be associated with tight intrauterine
• Back pain space and other conditions that are related to
• Limping and refusal to walk (especially in the same pathology of tight uterine cavity
toddlers who may not be able to communi- (e.g., congenital dysplasia of the hip or meta-
cate the fact of having back pain) tarsus adductus)
13 Orthopedics 471
a b
Fig. 13.3 Torticollis. A 1-year-old boy with congenital and chin directed to the left side. Patient has tight sternomas-
muscular torticollis. (a) Note the child’s head is tilted to the toid on the right side. (b) Ultrasound showed fibrotic mass in
right (the right ear is close to the right shoulder) with the face the sternomastoid (2.8 × 9 × 1.2 cm)
• Orthopedic causes of torticollis include: site side (see Fig. 13.3). Decreased neck
–– Congenital muscular torticollis, C1–C2 ROM to the opposite side
subluxation, and upper cervical spine • In older children with long-standing torticol-
anomalies lis, may also present with plagiocephaly,
–– Congenital muscular torticollis is the most facial asymmetry, and a unilateral epicanthal
common cause of torticollis due to fibrosis fold
of the sternomastoid muscle. • A palpable, firm mass can be present at the
–– May be related to birth injury or malforma- distal third of sternocleidomastoid muscle
tion within the muscle (see Fig. 13.3) • Diagnosis is based on history, physical exam-
• Non-orthopedic causes of torticollis include: ination, and normal radiographs
–– Sandifer syndrome (gastroesophageal • AP and lateral cervical spine radiographs to
reflux, hiatal hernia) rule out any bony malformation or C1–C2
–– Neoplasm (posterior fossa tumor and soft subluxation and are necessary to confirm
tissue tumor) diagnosis before starting physical therapy
–– Infection (retropharyngeal abscess)
–– Ocular Treatment
–– Neurological (syringomyelia and Arnold– • Congenital muscular torticollis: Aggressive
Chiari malformation) physical therapy for stretching sternocleido-
–– Dystonic drug reaction (metoclopramide) mastoid muscle
• Imaging: Radiography and CT of the cervical • Referral to orthopedic surgeon:
spine. MRI: If neurological cause is –– If no improvement (release of muscle is
suspected indicated if no improvement after 6 months
• Ultrasound helps to differentiate congenital of physical therapy)
muscular torticollis from other pathologies – – For those who present after 1 year of age
• Ophthalmology and neurology consult may
be needed if no identifiable cause can be
found Klippel–Feil Syndrome
Congenital Muscular Torticollis Background

• Child will have head turned to one side in • Congenital fusion of cervical vertebrae (fail-
combination with rotation of face to the oppo- ure of segmentation)
Diagnosis • Patients may present with renal anomalies or

• Clinical triad: Short-webbed neck, low hair- pulmonary disorders
line, restriction of neck motion (this may
expose the child to increased risk of neck
injuries due to decreased flexibility) Atlantoaxial Subluxation
• In adulthood, patients may develop neck pain
or neurological disorders as a result of disk Background
degeneration and spinal stenosis • Fixed rotation of C1 on C2
• Associated anomalies: Sprengel deformity • Causes: Retropharyngeal irritation (Grisel
(high scapula); cervical scoliosis; thoraco- syndrome), trauma, or Down syndrome
lumbar anomalies; genitourinary system
Diagnosis
anomalies (unilateral renal agenesis, dupli-
• Imaging: Dynamic CT (CT with head
cating renal collecting system, horseshoe kid-
straightforward and then rotated to right and
ney); auditory system anomalies; heart and
left) will show fixed rotation of C1 on C2 that
neural axis anomalies
does not change with head position
• Imaging: Radiographs of the cervical spine
(will show the vertebral fusion) Treatment:
• MRI can detect neural compression or intra- • If subluxation is less than 1 week: NSAIDs,
thecal anomalies (e.g., syringohydromyelia, soft collar, and stretching exercise program.
diastematomyelia) Most cases will improve
• Screening for associated anomalies, e.g., tho- • If subluxation is more than 1 week:
racolumbar radiograph, renal ultrasound Orthopedic/neurosurgical referral for possi-
ble need for traction (if subluxation is 1-week
Treatment
to 1-month duration) or fusion of the upper
• Most cases have near normal function and
cervical spine (for subluxation more than
need no treatment
1 month)
• If neurological or musculoskeletal problems,
orthopedic referral
BACK DISORDERS
Sprengel Deformity
Back Pain
Pathology
• Congenital elevation of scapula Background
• Occurs more frequently in female • Common in adolescents and uncommon in
young children
Clinical presentation • Most cases of back pain in children have no
• Shoulder asymmetry and limited shoulder identifiable cause
abduction • The etiology can range from simple benign
• Patients may complain of neck or shoulder pains causes, e.g., mechanical back strain, to very
serious causes, e.g., malignancies
• Presents in 35% of children with Klippel–Feil Causes
syndrome • Infections: Diskitis, osteomyelitis
• Anomalies in clavicles, ribs, and shoulder • Tumors: Osteoid osteoma or malignant
musculature tumors
13 Orthopedics 473
• Bone cyst: Unicameral or aneurysmal

• Spine: Herniated intervertebral disc, spondylol-
ysis, spondylolisthesis, Scheuermann kyphosis
• Mechanical: Heavy backpack, musical instru-
ment, or poor mechanics
• Postural hump back; activity related or pro-
longed sitting
Clinical approach and diagnosis

• History: Fever, chills, weight loss, loss of
appetite, loss of bladder or bowel control, and
unrelenting pain are all red flags of serious
causes
• Physical examination: Inspect the spine for
any deformities, sacral dimple, or swelling;
assess for leg-length discrepancies; gait
observation and neurological examination Spondylolysis Spondylolisthesis
Fig. 13.4 Spondylolysis is the presence of defect in the pars

Investigations of the vertebra. Spondylolisthesis is the “slippage” of the
• Depending on history and physical vertebra above in relation to the vertebra below
examination
• Best initial study is radiograph prior to any • The condition is present in about 7% of ado-
advance imaging lescents and in up to 20% of participants in
–– Thoracic and lumbar AP and lateral views sports that involve repeated extension of the
• Bone scan and MRI are helpful if the diagno- back (football, gymnastics, and diving).
sis cannot be made by history, physical exam- • Most commonly affected vertebra is L5, less
ination, and radiographs common is L4
• Laboratory studies: CBC, ESR, and CRP if
concern about infection or malignancies, uri- Diagnosis
nalysis if urinary tract infection is suspected, • The condition is asymptomatic in the major-
and human leukocyte antigen (HLA)-B27 if ity of cases
concern about ankylosing spondylitis or • The most common cause of non-muscular
Reiter syndrome back pain in adolescents, low back pain that
increases with extension of the spine
Management • Straight leg raising test: Pain in the posterior
• Treatment of underlying cause thigh but usually does not extend distal to the
• Limit backpack weight to no more than 15% knee (hamstring tightness)
of body weight or use rolling bag instead of a • Imaging:
backpack –– Spondylolysis can be found in the radio-
graph as an accidental finding
–– The defect can be seen in the lateral view
Spondylolysis of the lumbar spine, but it is more obvious
in the oblique view (Scottie dog with a col-
Background lar appearance) (Fig. 13.5)
• Spondylolysis is a bone defect in pars interar- –– CT scan will show the defect in the pars
ticularis of the vertebra (Fig. 13.4) interarticularis
a b c
Normal Spondylolysis
Fig. 13.5 Scottie dog collar sign. (a) Oblique view of the appearance of collar in the neck. (c) Oblique radiograph
lumbar vertebrae has the shade of Scottie dog. (b) With showing the defect in the pars interarticularis and Scottie dog
spondylolysis, the defect in the pars interarticularis gives the collar sign (arrow)
–– Bone scan with single-photon emission CT Diagnosis

(SPECT) can help to differentiate acute • Low back pain with extension activities
cases from chronic ones • Hamstring tightness
• Radiographs: Forward slippage of L5 over S1
Treatment • The degree of slippage is expressed as a per-
• NSAIDs and rest from the sport until the pain centage of the vertebral width
decreases
• Adolescent can resume sport activity when Treatment
they are pain-free • Orthopedic referral: Surgical treatment is
• Brace (lumbar corset) if the pain does not usually needed for high slip (> 50%)
improve with rest. Acute lesion can be treated • No contact sports if the slippage is more than
with more aggressive immobilization (thora- 50% of the vertebral width
columbar–sacral orthosis (TLSO)
• Orthopedic referral if no improvement (sur-
gery is rarely indicated in spondylolysis) Scoliosis
Background
Spondylolisthesis • Lateral curvature of the spine associated with
a rotational element
Background • Types of scoliosis:
• Forward slippage of upper vertebra in rela- –– Congenital: Due to bony deformity (verte-
tion to the vertebra below (see Fig. 13.4) bral column or chest wall)
• There are two types of spondylolisthesis in –– Neuromuscular: Due to neuromuscular
children and adolescents: causes (e.g., cerebral palsy, high-level
–– Dysplastic: Due to dysplastic lumbosacral spina bifida, traumatic spinal cord injury,
articulation, about 15% of cases muscular dystrophies)
–– Ischemic: Due to pars defect (spondyloly- –– Syndromic: Almost all syndromes can be
sis), most common type (about 85%) associated with scoliosis (e.g., dysplasias,
13 Orthopedics 475
connective tissue disorders, e.g., Marfan

syndrome, osteogenesis imperfecta, Prader–
Willi syndrome, neurofibromatosis)
–– Idiopathic: Most common cause. No
underlying cause can be identified.
Idiopathic scoliosis is further classified
according to the age of onset into:
◦◦ Infantile (scoliosis starts in the first
2 years of life)
◦◦ Juvenile (starts between 3 and 9 years
old)
◦◦ Adolescent (starts at or after the age of
10 years), which is the most common
type (adolescent idiopathic scoliosis)
Adolescent Idiopathic Scoliosis (AIS)

Background
• The condition runs in families (genetic pre-
disposition). More common in girls
• The curve continues to progress as long as the
child is growing. At the end of skeletal growth,
most curves will stop progression except for
large curves
• The curve of the AIS progresses maximally in
the period of “peak height velocity” or “rapid
growth phase.” This period is 1 year before
menarche age in girls
Diagnosis Fig. 13.6 Scoliometer. A 14-year-old girl with adolescent

• The condition is usually asymptomatic idiopathic scoliosis. (a) Scoliometer shows 7° of asymmetry
• In advanced condition, the deformity can (arrow). (b) Radiograph shows 31° at mid thoracic level
become more obvious:
–– Unequal shoulder level, unequal breast • Radiographs: The curve of the scoliosis is
sizes, and leaning toward one side measured with Cobb angle (see Fig. 13.6).
• Pain is not a symptom of AIS. If there is pain, The typical curve is right thoracic (convexity
MRI is recommended is toward the right)
• Physical exam: The ADAM forward-bending • Risser stage indicates the stage of skeletal
test will show thoracic hump maturity (Fig. 13.7). It depends on the ossifi-
• Motor, sensory, and reflexes of the lower cation of the iliac apophysis, which proceeds
extremities are normal from lateral to medial
• Scoliometer (a leveling assessment device
Treatment
used to objectively assess if one side of the
• Indication for referral to orthopedic surgeon:
body is higher than the other side with for-
–– Curves more than 20°
ward-bending) will show 7° or more of rota-
–– Curves more than 7° rotation by
tion (an indication for referral to orthopedic
scoliometer
surgeon) (Fig. 13.6)
a b • Pathology: Osteochondritis of the growth

plate of the vertebra. This will cause abnormal
growth of the vertebra with anterior wedging
3 4 5
2 • More common in adolescent boys
1
Diagnosis
• Deformity (bent back deformity). The defor-
mity is fixed and cannot be corrected by
straightening the back (in contrast to postural
kyphosis)
• Mid-back pain
• Neurological exam of the lower extremity:
Fig. 13.7 Risser sign. Fusion of the iliac apophysis pro- Usually normal (rarely, with advancing dis-
ceeds from lateral to medial. Complete fusion indicates
Risser stage 5. Radiograph shows Risser stage 4 (the apoph-
ease, neurological deficits can occur in lower
ysis is ossified from medial to lateral but still not fused with extremities)
the iliac bone; arrows point to the open growth plate) • Lateral radiograph of the spine shows
increased thoracic kyphosis with minimum of
• Indications for obtaining MRI for patient three consecutive vertebrae of more than 5°
with AIS: anterior wedging (Fig. 13.8)
–– Pain
–– Left thoracic curves Treatment
–– Abnormal neurological exam • Physical therapy: Thoracic extensor strength-
–– Infantile and juvenile scoliosis (curves that ening and hamstring stretching exercises
develop before the age of 10 years; due to • Refer to orthopedics: Bracing for curves less
high incidence of intrathecal anomalies, than 70° if the child still has more than 2 years of
e.g., syringomyelia) skeletal growth. For curves more than 70°, pos-
• Indications for bracing: sible surgical treatment to correct the deformity
–– Patients with significant skeletal growth • Most important surgical indication is
remaining and more than 5° of curve esthetic—unacceptable appearance
progression • Persistence of back pain and neurological
–– Curves more than 25° manifestation are other indications for sur-
• Indications for surgery gery but less common
–– Thoracic curves of more than 50° in skele-
tally mature children
–– Thoracic curves of more than 45° in skele- HIP DISORDERS
tally immature children
evelopmental Dysplasia of the Hip
D
(DDH)
Scheuermann Kyphosis
Background
Background • Ranges from complete dislocation of the hip
• Juvenile developmental disease with joint (the femoral head is outside the acetabu-
increased thoracic or thoracolumbar kypho- lum) to dysplasia of the acetabulum (shallow
sis due to structural deformity of the spine acetabulum)
with increased anterior wedging of the • More in: Female, firstborn, family history,
vertebrae breech presentation
13 Orthopedics 477
Fig. 13.8 Scheuermann
kyphosis. (a) A 14-year-
old boy with increased
thoracic kyphosis. (b)
Lateral thoracic
radiograph shows
thoracic kyphosis
between T1 and T12 of
67 degrees. (c) Close
view of the vertebrae
shows anterior wedging
of the vertebra (anterior
part of the vertebra
narrower than the
posterior part)
Fig. 13.9 Dynamic a b
ultrasound. Assessment
of the hip position by
ultrasound during various
positions. (a) To the left
with hip adduction, the
femoral head (dotted
circle) lies outside a line
along the pelvic bone
(dotted line). (b) With hip
abduction, partial
reduction occurs
• Can be associated with other conditions • Toddlers and children: Limping (unilateral
related to tight intrauterine position (e.g., tor- cases) or waddling gait (bilateral cases); limb
ticollis and metatarsus adductus) length discrepancy (dislocated side is shorter);
limited abduction of the affected side
Diagnosis • The limb length discrepancy can be
• In neonatal period: Screening all newborns detected by Galeazzi sign (flexing the hip
by Barlow or Ortolani test and knee and comparing the knee height)
• Hip ultrasound (before 4 months of age) or (Fig. 13.11) [1]
plain radiographs (after 4–6 months) will
show the dislocation and/or dysplasia Risk factors for which the pediatrician may
(Figs. 13.9 and 13.10) consider an imaging study in the child with a
• Females with breech presentation or positive normal screening with physical examination
family history should be screened using imag- are [2, 3]:
ing study in addition to the physical exam • Breech position in the third trimester—both
• Whether by risk factors or by suspicious males and females
physical examination, it is best to defer diag- • Family history of DDH
nostic hip ultrasound until age 6 weeks
• History of abnormal hip physical examina-

tion in the neonatal period, which subse-
quently normalizes
• History of improper swaddling:
–– If parents choose to swaddle their infants,
encourage hip-healthy swaddling that allows
freedom of hip motion and avoids forced
position of hip extension and adduction
Treatment
• Orthopedic referral (Pavlik harness for chil-
dren less than 6 months; closed reduction and
casting for children 6–18 months; open reduc-
Fig. 13.10 Anteroposterior pelvis radiographs of a
tion for children > 18 months)
14-month-old girl with developmental dysplasia of the left
hip. The radiograph shows the ossific center on the left side
(arrow) smaller than the right side and lying in the upper Legg–Calve–Perthes Disease
lateral quadrant of the crossing two lines (Hilgenreiner and
Perkins; the normal right side lies in the lower medial quad- Background
rant). The Shenton line (curved line across the obturator
• Avascular necrosis of the head of the femur in
foramen and lower border of the neck) is intact on the right
side (continuous curved line) and broken on the left side a growing child (skeletally immature)
(curved dotted line). The dislocated side shows increased • Self-limiting disease; the pathological pro-
acetabular index (the angle between the Hilgenreiner line cess usually takes about 24–36 months
and line from the triradiate to the lateral part of the
acetabulum)
a b
Fig. 13.11 A 10-month-old infant with developmental dys- side will be at a lower level compared to the right; this indi-
plasia of the left hip. (a) Notice the limited abduction of the cates limb length discrepancy, with the dislocated side
left hip. (b) Galeazzi sign: While flexing both legs and put- shorter than the normal side
ting the feet together, the knee on the short (left, dislocated)
13 Orthopedics 479
Acetabulum
Proximal femoral Severe SCFE

epiphysis
Metaphysis
Mild SCFE
Fig. 13.13 The pathology of slipped capital femoral epiphysis

(SCFE) . The proximal femoral epiphysis is contained in the
acetabulum and does not move, while the slippage occurs when
Fig. 13.12 An 8-year-old boy with 1-year history of Perthes the metaphysis starts to move in relation to the epiphysis
disease in the left hip
• Can be stable (patient is able to bear weight
Diagnosis on the affected side) or unstable (patient is
• More in boys between the ages of 4 and 8 years not able to bear weight on the affected side
• Limping with or without crutches)
• Hip pain or knee pain (always consider hip • Can lead to avascular necrosis of the femoral
etiology in any child presenting with limping head due to stretching of the vessels supply-
and knee pain) ing the femoral head by the displacement of
• Hip radiographs will show the collapse and the proximal metaphysis
increased density of the femoral head
(Fig. 13.12) Diagnosis (Table 13.3)
• More in obese African American boys
Treatment between 12 and 14 years
• Orthopedic referral • Clinical presentation: Hip or knee pain
• Symptomatic treatment (mostly in children (referred pain); limping, external rotation of
less than 6 years), through avoiding sports the affected extremity
and the administration of nonsteroidal anti- • Hip radiographs will show the displacement
inflammatory drugs (NSAIDs) for pain, or (Fig. 13.14)
surgery (pelvic or femoral osteotomy)
Treatment
• Admission to the hospital and urgent orthope-
Slipped Capital Femoral Epiphysis dic consult
(SCFE)
Background KNEE PAIN AND INJURIES
• Displacement of the proximal femoral
metaphysis in relation to the capital (proxi- M
eniscal Injury of the Knee
mal) femoral epiphysis (Fig. 13.13)
• Most cases are idiopathic; some cases are Background
related to endocrinopathies (hypothyroid- • Anatomy of the menisci: Two cartilaginous
ism or hypopituitarism) or renal crescent-
shaped structures that act like a
osteodystrophy cushion inside the knee (Fig. 13.15)
Table 13.3 Difference between developmental dysplasia of the hip (DDH), Legg–Calve–Perthes disease (LCPD), and
slipped capital femoral epiphysis (SCFE)
DDH LCPD SCFE
Toddler < 3 years 3–10 years > 10 years
Painless limp (infants and toddlers) Painful limp Painful limp
Older children: vague activity-related Hip pain or knee pain Hip pain or knee pain
discomfort due to leg-length
discrepancy
Positive Ortolani and Barlow signs Limited hip motion Limited hip motion
Galeazzi positive (unilateral) Decreased internal rotation and abduction Decreased internal rotation
Waddling gait (bilateral)
Hip ultrasound < 6 months Pelvis radiograph: Anteroposterior (AP) Pelvis radiograph: AP, and frog-
Pelvis radiograph > 6 months and frog-lateral views lateral views
Referral to orthopedic Referral to orthopedic Urgent referral to orthopedic
a b • The medial meniscus is more prone to injury

because it is more fixed to the joint capsule
and more likely to be caught in between
femur and tibia in case of injury
• More common in adolescents as a result of
twisting injury to the knee
• Can be associated with other ligament inju-
ries like anterior cruciate ligament (ACL)
injury
• The tears are classified according to the shape
and the site
–– According to the shape: Longitudinal
(most common), radial, flap, or bucket
Fig. 13.14 A 13-year-old boy with right hip and knee pain handle tear (Fig. 13.16)
of 2 weeks duration. Lateral radiographs of both hips are pre- –– According to the site: Peripheral tear (has
sented in this figure. The Klein line (the black line) is drawn the highest healing potential as it has the
along the anterior femoral neck. Normally (left), the Klein best blood supply); middle; central (has the
line should intersect part of the epiphysis of the proximal
least healing potential due to poor blood
femur (an arrow is pointing to the anterior edge of the epiph-
ysis). Right (slipped capital femoral epiphysis; SCFE), the supply)
Klein line does not intersect any part of the epiphysis
Posterior
Diagnosis
PCL
• Injury to the knee followed by pain and swell-
ing. The swelling usually develops a few
hours after the injury (in contrast to ACL
injury in which the swelling develops imme-
Medial
diately after injury)
Lateral
• Locking, “catching” of the knee
• Positive McMurray sign (extension of the
Medial
meniscus knee with internal and external rotation by
the examiner); apply grinding (downward
Lateral
meniscus
ACL push on the foot with the patient lying prone
anterior and the knee flexed 90°) tests and deep squats
(Fig. 13.17)
Fig. 13.15 Medial and lateral meniscus
13 Orthopedics 481
Fig. 13.16 Types of

meniscal tears
longitudinal Bucket handle Displaced Bucket handle
Flap Radial
Fig. 13.17 McMurray
test: (a) The knee is
flexed with one hand
holding the knee at the
joint line and the other
knee holding the foot. (b)
The knee is flexed, and
the leg is put in external
rotation and valgus while
extending the knee. (c, d)
This is repeated with leg
in varus and internal a
rotation. Pain or a “click”
constitutes a positive b
McMurray test
c d
• Plain radiographs (AP, lateral, and sunrise) Treatment

to exclude fractures or other bone • Most meniscal tears in adolescents are longi-
pathology tudinal peripheral tear that have good healing
• MRI can detect the meniscal tear and can also potential (in contrary to adults in which most
show associated injuries (e.g., ACL injury) tears have minimal healing potentials)
• Acute management: RICE (rest, ice, com- due to increased sports participation at
pression, and elevation) younger age
• Physical therapy for ROM exercises and • More common in adolescent females playing
strengthening sports with cutting movements (e.g., soccer)
• Return to sports: Full ROM (compared to the • The injury occurs secondary to direct trauma
other knee) with no pain to the knee or noncontact twisting or hyper-
• Indication for orthopedic referral: extension injury to the knee
–– Failure of conservative therapy • May be associated with injuries to medial and
–– Bucket handle and flap tears lateral collateral ligaments and menisci
–– Associated ACL injuries
Diagnosis
• Child will describe injury followed by “pop-
Medial Collateral Ligament Injury ping” of the knee and immediate swelling
(MCL) with inability to bear weight
• Marked swelling (hemarthrosis)
Background • Stressing the knee joint: Positive Lachman
• Anatomy: Extends from the medial femoral and anterior drawer tests; cannot be per-
epicondyle to the medial aspect of the tibia. It formed in the acute setting because of pain
consists of two parts: superficial and deep • Imaging: AP, lateral, 20° tunnel, and sunrise
• MCL: Primary restrain of the knee joint against radiographs to rule out fracture
drifting into valgus (the tibia points laterally) • MRI is diagnostic for ACL disruption. Also
assess the integrity of menisci, collateral liga-
Diagnosis
ments, and chondral surfaces
• Pain in the medial aspect of the knee follow-
ing valgus injury Management
• Instability of the knee on valgus stress • Initial conservative management: Rest, ice,
• Radiograph: AP, lateral, and sunrise view to activity modification, bracing, and physical
exclude fractures therapy
• MRI will show the injury to the medial • Early orthopedic referral for surgical consider-
collateral ation: Surgical reconstruction (by graft whether
autograft (from the patient him/herself) or from
Treatment
donor (allograft) is the standard of treatment if
• Most MCL injuries can be treated conserva-
the patient wants to continue sport activity
tively: RICE, physical therapy for ROM exer-
• Reconstruction by graft requires drilling and
cises, and strengthening
passing tissues across the growth plate of the
• Return to sports: When the patient has full
distal femur and proximal tibia, which may
ROM with no pain
affect these growth plates. This is of more
concern in younger children
nterior Cruciate Ligament (ACL)
A
Injury
Osteochondritis Dissecans
Background
• Anatomy: Extends from the anterior part of Background
the tibia to posterior femoral notch. It pre- • Affection of a piece of bone close to the artic-
vents anterior displacement of the tibia on the ular cartilage that becomes avascular and ulti-
femur mately separates from the surrounding bone
• Most common ligamentous knee injury with • Etiology unknown but may be related to
increasing incidence in adolescent population repetitive trauma
13 Orthopedics 483
a b
Fig. 13.18 Osteochondritis dissecans. Radiographs of left Fig. 13.19 Sunrise view can show the position of the patella
knee (a) anteroposterior, (b) notch view, showing osteochon- in the trochlear groove. Computed tomography (CT) and
dral defect on the medial femoral condyle magnetic resonance imaging (MRI) can better delineate the
tilt of the patella and trochlear hypoplasia
• Most common site is the knee but can also
occur in the ankle and elbow
the patella is unstable and tilting toward the
• More common in adolescents
side, but no full dislocation)
Diagnosis (Osteochondritis Dissecans of the Knee) • Common in adolescent females
• Vague knee pain, more with activity • Usually associated with knee pain
• Mild recurrent effusion • Predisposing factors for recurrent dislocation
• Loss of extension or flexion if the lesion is and subluxation:
detached and loose in the knee, blocking –– Dysplastic trochlear groove
movement –– Patella alta (high-riding patella)
• Radiographs: A radiolucent area may be seen –– Increase Q angle (angle between pull of
surrounding the lesion. In advanced cases, the quadriceps muscle and patellar tendon)
affected lesion may be fragmented and –– Genu valgum
detached (Fig. 13.18) –– Increased femoral anteversion
–– External tibial torsion
Treatment
• Orthopedic referral. Most cases (especially in Diagnosis
young children) will heal spontaneously • General examination for signs of increased
without surgery laxity (e.g., elbow hyperextension)
• Parapatellar tenderness
• Mild effusion
Recurrent Patellar Dislocation/ • Specific test for patellar stability:
Subluxation –– Positive J sign: Patella will deviate later-
ally at the end of knee extension
Background –– Apprehension sign: Extension of the knee
• Patients will complain of history of repeated with laterally directed pressure on the
dislocation events (the patella will lie on the patella will give positive result (apprehen-
lateral side of the knee and has to be reduced sive facial expression)
back by the patient herself or someone else) • Radiographs: Sunrise view will show the lat-
or subluxation events (the patient feels that eral tilt of the patella (Fig. 13.19)
Treatment ◦◦ The normal adult alignment (7° of val-

• After first dislocation: Knee immobilizer for gus) is usually reached by the age 8 years
1–2 weeks followed by physical therapy –– Blount disease (see below)
• Recurrent dislocation/subluxation: Therapy –– Rickets
referral for isometric quadriceps-strengthen- –– Achondroplasia
ing exercise and vastus medialis obliquus
(VMO) strengthening Diagnosis
• Orthopedic referral: Surgery is indicated if • Increase intercondylar distance (distance
conservative treatment fails between the two medial femoral condyles;
see Fig. 13.20)
• Radiographs will identify the underlying
ANGULAR DEFORMITIES pathology
Genu Varum (Bowleg) Treatment

• Physiological cases: No treatment needed,
Background should improve by the age of 3 years
• Lower limb deformity in which the lower legs
are pointing toward the midline (Bowleg) Indication for plain radiographs in cases of
(Fig. 13.20) genu varum (possible need for orthopedic
• Common causes of genu varum in children referral):
include: • Persistence of genu varum after 24 months or
–– Physiological development up to the age of worsens after age 1 year
2 years: • Unilateral genu varum
◦◦ The normal alignment of children is • Severe genu varum (clinical angle between
genu varum until the age of 2 years, and thigh and leg of more than 20° or intercondy-
then alignment changes to valgus which lar distance of more than 6 cm)
reaches maximum around the age of • If suspecting general medical condition (e.g.,
3 years rickets)
Fig. 13.20 (a)

Intermalleolar distance.
This distance increases in
cases of genu valgum. (b)
Intercondylar distance:
This distance increases in
cases of genu varum. (c)
A 3-year-old boy with
genu varum and
intercondylar distance of
more than handbreadth
a inter malleolar distance b inter-condylar distance

13 Orthopedics 485
Genu Valgum (Knock-Knee) • Radiographs will identify the underlying

pathology
Background
• Lower limb deformity in which the lower legs Treatment
are pointing away from the midline (knock- • Physiological cases: No treatment needed,
knee) (Fig.13.21) should improve by age of 8 years. Other
• Common causes of genu valgum in children causes of genu valgum will require orthope-
include: dic consultation
–– Physiologic genu valgum (around the age
of 3 years) Blount Disease (Tibia Vara)
–– Metabolic: Rickets and renal
osteodystrophy • Developmental deformity resulting from
–– Post-traumatic physeal arrest abnormal endochondral ossification of the
–– Proximal tibial fractures medial aspect of the proximal tibial physis
leading to varus deformity and internal rota-
Diagnosis
tion of tibia
• Increased intermalleolar distance (distance
• More common in obese African American
between the two medial malleoli; see
children
Fig. 13.21)
• Types:
–– Infantile type
◦◦ Starts around 3 years of age
◦◦ More progressive than adolescent type
due to greater growth potential
◦◦ Radiographs will show the varus defor-
mity with medial proximal tibial growth
plate abnormalities (Fig. 13.22)
a b
Fig. 13.22 Radiological changes in Blount disease. (a)

Long radiographs (scanogram) of a 3-year-old girl showing
the proximal tibial metaphyseal beaking (arrow). (b) A
Fig. 13.21 Physiological genu valgum. A 30-month-old 4-year-old boy with depression of the medial tibial plateau
boy with physiological genu valgum. Notice the increased and fusion of the growth plate on the medial side (arrow).
angle between the leg and the thigh and the increased inter- Note the difference between the medial and lateral sides of
malleolar distance (double-headed arrow) the tibial growth plate
Fig. 13.23 Radiographic a b
changes of adolescent
tibia vara. A 15-year-old
black male presented
with unilateral adolescent
tibia vara on the right
side. (a) Scanogram
shows varus alignment
on the right side with the
mechanical axis of the
lower extremity medial to
the joint. (b) Radiographs
of the leg show varus
deformity of the proximal
tibia
◦◦ Treatment: Knee brace to correct varus F emoral Anteversion

before the age of 3 years. If no improve-
ment or if the patient is older than 3 years, Background
orthopedic referral for surgical treatment • Femoral anteversion is the angle between the
◦◦ Surgical intervention is contraindicated neck of the femur and the shaft in the sagittal
in children younger than 2 years plane (Fig. 13.24)
–– Adolescent type • This angle is about 40° at birth and decreases
◦◦ Occurs in adolescents (especially obese as the child starts walking. It reaches the adult
boys) (Fig. 13.23) normal value (about 17°) by the age of 8 years
◦◦ Treatment is by referral for orthopedic • Diseases that affect the child’s ability to walk
intervention (e.g., cerebral palsy) will result in the child
continuing to have increased angle of femoral
anteversion
• Excess femoral anteversion is the most com-
INTOEING mon cause of intoeing between the ages of 3
and 8 years
Three Main Causes
• Excess femoral anteversion Diagnosis
• Internal tibial torsion • Hip internal rotation exceeds hip external
• Metatarsus adductus rotation (Fig. 13.25)
13 Orthopedics 487
Fig. 13.24 Femoral a b
anteversion. (a) The
angle between the
femoral shaft and the
femoral neck in the
sagittal planes. (b, c)
Notice when the femur
rests on the flat surface,
the femoral head is
elevated on that surface
by the anteversion of the
neck c
Fig. 13.25 A 12-year- a b

old girl with severe
intoeing (notice the
inward position of both
patellae) (a).
Examination shows
increased hip internal
rotation (b) compared to
external rotation (c)
Treatment I nternal Tibial Torsion

• No treatment is required, as the condition
usually resolves spontaneously around the Background
age of 8 years • Inward rotation of the shaft of the tibia. It is
• Bracing and orthotics do not change the natu- considered normal finding in newborn/ infants
ral history of the condition due to intrauterine position
Fig. 13.26 Assessment of

the tibial torsion (thigh foot
angle). The child lies prone
on the table, and the
physician assesses the angle
between the thigh and foot
with the knee flexed
• Internal tibial torsion is the most common

cause of intoeing in infants around the age of
2–3 years
Diagnosis
• With the child lying prone flexing the knee,
the foot will be pointing inward in relation to
the thigh (thigh foot angle) (Fig. 13.26) [1]
Treatment
• No treatment is required. The condition usu-
ally resolves spontaneously over the first few
years of life
Fig. 13.27 Metatarsus adductus. A 4-year-old with moder-
ate metatarsus adductus on the left side and severe on the
Metatarsus Adductus right side (patient is prone with flexed knee). Notice the
curved lateral border of the foot
Background
• Adduction and inward position of the fore- Diagnosis
foot compared to the heel (Fig. 13.27) • The foot has a curved lateral border (instead
• May be related to intrauterine position and of straight border)
may be associated with other conditions • Differentiated from clubfoot by absence of
related to uterine malposition (e.g., hip dys- ankle equinus (plantar flexion) and hindfoot
plasia, torticollis) varus (inward deviation of the heel)
13 Orthopedics 489
Treatment Diagnosis
• Most infants will improve without • Rigid deformity (cannot be corrected by the
interference examiner)
• If the condition persists beyond 6 months of • Clubfoot has three main deformities
age and the deformity is rigid, orthopedic (Fig. 13.28)
referral for either serial casting or bracing. –– Ankle and foot equinus (plantar flexion of
Surgery is rarely indicated the ankle and the foot)
–– Hindfoot varus (inward deviation of the
heel)
–– Forefoot adduction (inward position of the
FOOT DISORDERS forefoot in relation to the hindfoot)
• Other components: High-arched foot (cavus)
Clubfoot (Talipes Equinovarus) and internal tibial torsion of the leg
Background • Clubfoot is a clinical diagnosis; no radio-
• Complex rigid deformity of the ankle and the graphs are needed
foot
Treatment
• Unknown etiology: May be related to muscu-
• Orthopedic referral: Two treatment options
lar, neurogenic, genetic, and/or connective
are currently utilized:
tissue etiologies
–– Serial casting: weekly change of cast
• Affects about 1 in 1000 live births. More
–– Physical therapy and stretching
common in boys (2:1). 50% of cases are
• Early orthopedic referral is needed to ensure
bilateral
early start of treatment
• Types:
• After correction of the foot deformity, a brace
–– Idiopathic: No other congenital condition
(corrective shoes with a bar in between the
can be found. Most common type
shoes to turn the feet outward) should be used
–– Postural: Due to posture of the newborn in
for 2–3 years to prevent the recurrence
the uterus. The deformity can be corrected
easily by the examiner. Not considered real
clubfoot Calcaneovalgus Foot
–– Syndromic: Some congenital conditions
are associated with clubfoot, such as Background
arthrogryposis and diastrophic dwarfism • A condition in the newborn in which the foot is
–– Neuromuscular conditions: Myelomeningocele in excessive dorsiflexion and valgus (Fig. 13.29).
and cerebral palsy It is related to intrauterine position
Fig. 13.28 Clubfoot. A a b

2-week-old girl with left
clubfoot. Notice the
deformity of the left foot
(equinus, varus, forefoot
adduction, and cavus).
On the left (a), notice the
hindfoot varus. On the
right (b), notice the
forefoot adduction and
equinus
Fig. 13.29 Calcaneovalgus a b
foot. (a, b) Newborn baby
with right foot deformity.
The foot is in valgus and
dorsiflexion (calcaneus
position). No treatment
required, as the condition is
self-limiting
Fig. 13.30 Cavus foot. a b

A 15-year-old boy with
Charcot–Marie–Tooth
disease. Patient has right
foot high-arch deformity
(cavus). Lateral
radiograph of the foot
(standing) shows
increased lateral talar–
first metatarsal (Meary’s)
angle
Diagnosis Diagnosis
• The foot is in excess dorsiflexion (calcaneus • The foot will have high-arched appearance
position of the foot) and valgus to the degree • Thorough neurological exam must be done to
that the dorsum of the foot is touching the identify possible underlying cause
front of the tibia. • Radiographs: The lateral talar–first metatar-
• The ankle and hindfoot are flexible enough to sal (Meary’s) angle is more than 5° convex
easily correct the deformity dorsally (normally, it should be 0°)
Treatment Treatment
• Most cases do not require treatment, as they • Identification and treatment of the underlying
will improve with growth within a few weeks cause
• Neurology/neurosurgery and orthopedic sur-
gery referral
Cavus Foot
Background latfoot (Pes Planus)
F
• High-arched foot (Fig. 13.30)
• Cavus foot is usually an indication of neurologi- Background
cal pathology (e.g., Charcot–Marie–Tooth dis- • The medial arch of the foot does not develop
ease), spina bifida (sacral-level affected), lipoma until the age of 4 years and reaches close to
of the cord, or other intrathecal pathology the adult value by the age of 8 years
13 Orthopedics 491
Fig. 13.31 Flexible a b c
flatfeet. A 9-year-old girl
with bilateral flexible
flatfeet. When patient
stands, there is loss of
arch (arrow; a). When
she tiptoes (b) or with
dorsiflexion of the big toe
(c), there is restoration of
the arch (dotted arch)
• Flexible flatfoot: –– Achilles tendon stretching for children

–– Loss of the medial arch support when the with tight Achilles tendon
child stands. This is a normal finding in • Rigid flatfoot:
about 10% of the population –– Orthopedic referral
–– It is a universal finding in neonates and
toddlers and is associated with physiologi-
cal ligamentous laxity and excess fat at the T arsal Coalition
sole of the foot.
• Rigid flatfoot: Background
–– Due to foot pathology such as tarsal coali- • Abnormal connection (bridging) between
tion or congenital vertical talus two of the tarsal bones
• The condition usually starts as fibrous or car-
Diagnosis tilaginous connection and then matures to
• Loss of the arch of the foot (the heel will be in bony bridge between two bones by the
valgus) when the patient stands adolescence
• Flexible flatfoot: • The condition is usually asymptomatic and
–– With tiptoeing or with dorsiflexion of the bilateral. About 5% of the population has tar-
big toe (tightening of the plantar fascia), sal coalition
restoration of the arch (Fig. 13.31) • Most common coalition is calcaneonavicular
–– Normal subtalar joint movement (supina- and subtalar (talocalcaneal) fusion
tion/pronation of the foot)
–– The condition in most cases is asymptomatic.
Rarely, the condition can cause pain at the Diagnosis
medial aspect of the foot over the tarsal head • Usually presents around 10–14 years old
–– Some cases are associated with tight • Stiff flatfoot with foot pain
Achilles tendon. Other cases may be asso- • History of recurrent ankle sprains with per-
ciated with generalized laxity of the joints sistence of the pain after the injury
• Rigid flatfoot: • Decreased subtalar movement (supination
–– Rigid deformity that is not corrected by and pronation of the hindfoot)
tiptoeing or dorsiflexion of the big toe • Radiographs can show the bony fusion espe-
–– Decreased or absent subtalar motion cially calcaneonavicular type (anteater sign).
Subtalar (talocalcaneal) coalition is harder
Treatment to detect in plain radiographs. If radiograph
• Flexible flatfoot: is normal and the condition is suspected
–– Reassurance (the condition is a variation of clinically, CT of the foot is indicated
normal development) (Fig. 13.32)
a b c
Fig. 13.32 Calcaneonavicular coalition. An 11-year-old flatfoot with no arch and bony prominence of the calcaneus
boy with left flatfoot and valgus heel (a; dotted line) and foot (white arrow; anteater sign). Oblique radiograph (c) shows
pain for 6 months. Lateral standing radiograph (b) shows the calcaneonavicular coalition (black arrow)
Treatment Diagnosis
• If discovered accidentally during foot radio- • The child walks on his/her toes with no pain
graphs taken for other reasons: No treatment • Tight Achilles tendon especially with the
is needed. Orthopedic referral for symptom- knee extended
atic cases only
Treatment
• Toe walking is a normal variant in children
Tiptoe Walking younger than 3 years, and no treatment is
warranted in this age range.
Background • Unilateral toe walking should always be eval-
• Pattern of walking in which the child walks uated further, because it may indicate the
on his/her toes with ankle plantar flexion. If presence of hemiplegia, developmental dys-
no underlying neurological cause is identi- plasia of the hip, or leg-length discrepancy
fied, it is referred to as “habitual toe walking • Full neurological exam to exclude underlying
or idiopathic toe walking” neurological disease
• It is common in toddlers and young children • If the child had just learned how to walk, is
when they are starting to learn how to walk. less than 3 years old, or the toe walking is
Sometimes associated with autism or speech occasional:
delay –– Observation and reassessment after 6 months
• Other causes of tiptoeing (differential diag- • If the child is older than 3 years and the toe
nosis of idiopathic toe walking): walking is constant:
–– Cerebral palsy: Mild cerebral palsy is very –– Physical therapy for Achilles tendon
hard to differentiate from idiopathic toe stretching
walking. Upper extremities movement dur- –– If no improvement after 6 months of ther-
ing gait is normal in idiopathic toe walking apy: Orthopedic referral for botulinum
and restricted in mild cerebral palsy toxin injection of the calf muscle, Achilles
–– Duchenne muscular dystrophy: Positive tendon lengthening, or serial casting
Gower sign, pseudohypertrophy of the
calf, elevated creatine phosphokinase
(CPK) Ingrowing Toenail
–– Tether cord syndrome: Other neurologi-
cal manifestations (e.g., bladder Background
dysfunction) • The penetration of the border of the nail plate
–– Limb length discrepancy will cause unilat- into the nail fold causing pain and inflamma-
eral toe walking (on the short side) tion in the surrounding tissue (Fig. 13.33)
13 Orthopedics 493
• Etiology: Unknown; may be related to tight- straight across and avoid cutting back the lat-
fitting shoes, trauma to the toe, incorrect trim- eral margins; the nail edge should extend past
ming of toenails, and/or genetic susceptibility the nail fold)
• Frequent soaking of the foot in warm water
Diagnosis • Local antibiotic application (oral antibiotic
• Significant pain in the toe with inflammation can be prescribed if the infection is advanced)
of tissue surrounding the nail bed • Elevating the offending edge of the nail from
the soft tissue and placing a small piece of
Treatment gauze between the nail and the skin
• Proper care of the nail (comfortable wide toe • If no improvement with the above measures:
box or open-toed shoes; the nail should be cut Orthopedic or podiatry referral
FRACTURES
Salter–Harris Injuries
Background
• Injuries of the bone that go through the growth
plate (physis)
• Classification: Type I through type V
(Fig. 13.34)
• Complication of Salter–Harris injuries: These
fractures can cause injury to the growth plate
and possible growth disturbance
Fig. 13.33 A 6-year-old with an ingrown toenail. Notice the –– If the growth disturbance is through the
pocket of pus (arrows) whole growth plate (complete), it will
Fig. 13.34 Physeal a
(Salter–Harris) injuries
classification. (a, b, c)
Type II distal tibial
fracture before and after Normal Type I Type II Type III Type IV Type V
closed reduction. (d, e)
Type IV distal tibial b c d
fracture before and after
open reduction and
internal fixation
e
result in a short bone (and possible limb

length discrepancy)
–– If the growth disturbance is partial (only
part of the growth plate is affected), the
bone will grow in deformed position
Diagnosis
• Radiographs will show the fracture line pass-
ing through the growth plate (see Fig. 13.34)
• The growth disturbance is more common in
certain fracture patterns (types III and IV
injuries) and in certain growth plates (distal
femur and proximal tibia growth plates)
Treatment Fig. 13.35 Radiograph of a 12-year-old boy who fell down

• Urgent orthopedic referral. Physeal injuries and had pain over the clavicle. The radiograph shows a mid-
shaft clavicle fracture
heal faster than other fractures because they
occur through rapidly dividing cells; they
have to be reduced as soon as possible
Clavicular Fracture
Background
• A common fracture in pediatric patients due
to the superficial location of the clavicle
Diagnosis
• Pain, deformity, and swelling over the clavi-
cle after falling on an outstretched hand
• Radiographs will show fracture of the clavi-
cle with possible deformity (angulation and/
or displacement) (Fig. 13.35)
Fig. 13.36 Complete fracture of the proximal humerus.
Treatment Note the displacement of the fracture ends
• Arm sling for comfort. The child can take it
off when he/she feels more comfortable. No
need for the figure-of-8 sling. Fractured clav- Proximal Humeral Fracture
icle will heal with obvious bump (bony
callus) Diagnosis
• Indication for referral: Open fracture, frac- • Pain and swelling of the proximal arm
tures associated with neurovascular injuries, • Radiographs will show the fracture
markedly displaced or shortened fractures (Fig. 13.36)
13 Orthopedics 495
Treatment upracondylar Fracture of Humerus

S
• Most of the fractures of the proximal humerus
can be managed nonoperatively, especially in Background
young children. Immobilization of the arm in • Transverse fracture of the distal part of the
a sling humerus proximal to the articular surface
• Incidence: 60–70% of elbow fractures,
more common in boys, between 4 and
Humerus Fracture 7 years old
• Can be associated with many complications
Diagnosis (compartment syndrome, malunion, nerve
• Pain, swelling, and deformity of the arm injury)
• Can be associated with wrist drop due to
radial nerve palsy. The vast majority of these Diagnosis
palsies will improve spontaneously with no • Pain, swelling, and deformity of the affected
treatment needed elbow
• Radiographs will show the fracture (Fig. 13.37) • With marked displacement of the fracture
ends, bruises of the anterior elbow will occur
Treatment (the proximal fragment button through the
• Orthopedic referral is needed to this brachialis muscle)
condition • Radiograph will show the fracture line, which
• Most humeral shaft fractures can be managed passes across the supracondylar area
nonoperatively in braces (Figs. 13.38 and 13.39)
• According to the displacement, the fracture is
classified into:
–– Nondisplaced (type I), angulated (type II;
see Fig. 13.39), displaced (type III; see
Fig. 13.38)
a b
Fig. 13.38 Bruising of the anterior elbow with displace-

ment of the fracture in a 7-year-old girl who fell and has
obvious deformity of the left elbow. Cubital fossa shows
bruising (a) (arrow). Radiograph (b) shows type III supra
Fig. 13.37 Transverse fracture of the shaft of the humerus condylar fracture of the humerus with marked displacement
in an 11-year-old boy involved in an all-terrain vehicle of the fracture ends. The proximal fragment had “buttoned
(ATV) accident through” the brachialis muscle, causing this bruising
Fig. 13.39 Type II a b

supracondylar fracture of
the humerus. A 4-year-
old boy with left
supracondylar fracture of
the humerus type II
(notice the angulation of
the fracture ends in the
lateral view) (a), with no
displacement of the
fracture in the
anteroposterior view (b).
The treatment was closed
reduction and
percutaneous fixation of
c d
the humerus by K wires
(c, d)
Treatment
• Assess radial and ulnar pulses. If there is an
absent distal pulse or possible compartment
syndrome, urgent orthopedic consultation
• Assess nerve function
• Orthopedic referral for possible surgical
intervention:
–– Angulated/displaced supracondylar
humerus fracture (stages 2 and 3):
Treatment is closed reduction and percuta-
neous pinning (see Fig. 13.39)
Lateral Condyle Fracture

Background
Fig. 13.40 Type I supracondylar fracture of the elbow with • Fracture of the lateral condyle of the humerus
posterior fat pad sign (arrows) (which includes the capitellum)
• Incidence is about 10% of the fractures of the
–– For nondisplaced fracture, posterior fat pad elbow
sign will be seen in the lateral radiographs, • Can be complicated by nonunion
indicating blood in the joint from the
fracture (Fig. 13.40)
13 Orthopedics 497
a b a b
Fig. 13.41 Lateral condyle fracture. A 4-year-old boy fell

on an outstretched hand and had elbow pain and swelling.
Radiographs (a, b) show a lateral condyle fracture (arrow)
Fig. 13.42 Acute medial epicondyle fracture. A 13-year-old
boy who fell while playing basketball. Radiograph shows the
Diagnosis fracture displacement (a). The clinical picture shows the
• Pain, swelling, and deformity of the affected large bruising on the medial aspect of the elbow (b). Due to
elbow the amount of fracture displacement, surgery was done for
• Radiographs: The fracture line will pass open reduction and internal fixation (c)
through the lateral condyle and the capitulum
(Fig. 13.41) • Radiographs will show the fracture and dis-
placement of the medial epicondyle (Fig. 13.42)
Treatment
• Orthopedic referral. These fractures are prone Management
to develop nonunion • Orthopedic referral. In most cases, the frac-
• If nondisplaced: Casting with close follow-up ture can be managed conservatively with no
to detect possible displacement. If displaced, need for surgery
the fracture will require surgery. Displaced • Surgery is indicated in cases of fracture–dis-
fracture requires open reduction and internal location in which the fractured piece is incar-
fixation cerated in the joint (Fig. 13.43) or if there is
more than 20 mm displacement of the frac-
ture ends (see Fig. 13.42)
Medial Epicondyle Fracture
Background caphoid Fracture
S
• Can occur as a stress fracture (repeated stress
to the medial epicondyle during throwing Background
activities, which will result in the fracture • Most common carpal fracture in pediatric
with low-energy injury) or can also occur as patients
an acute fracture due to acute injury to the • Peak incidence at 15 years of age and rare
elbow before the age of 8
• Can be complicated by nonunion due to pattern
Diagnosis of blood supply. Fractures can result in disrup-
• Pain, swelling, and deformity of the affected tion of the blood supply to the bone, resulting
elbow in avascular necrosis and collapse of the bone
Fig. 13.43 Fracture a c d
dislocation of the medial
epicondyle. A 12-year-
old boy fell on his hand
while skating. He
dislocated his right elbow
(a). Closed reduction of
the elbow was done. Post
reduction radiographs (b,
c) showed incongruence
b
lateral view of the elbow;
compare with the normal
side (d). The medial
epicondyle can be seen in
e
the joint (arrows).
Surgery was done for
removal of the piece from
the joint and internal
fixation by screws (e)
Diagnosis
• Pain and swelling on the radial aspect of the
wrist
• Tenderness over the anatomical snuff box
• Radiograph with PA, lateral, oblique, and
scaphoid views (Fig. 13.44) can show the
fracture. High index of suspicion is required
for early diagnosis, as the radiographs may be
negative in the first 2 weeks
• MRI can be used in cases with negative radio-
graphs if the clinical suspicion of fracture is high
Treatment
• Initial suspicion of fracture with negative
radiographs: Treat as if a scaphoid fracture is Fig. 13.44 Scaphoid fracture. A 13-year-old child fell down
present. Place the child in short thumb spica while playing football. The patient had pain at the wrist cen-
splint for 1–2 weeks and then radiographs tered over the anatomical snuff box. Oblique radiograph
shows fracture of the scaphoid
repeated after 2 weeks
• If repeat radiographs are negative and child’s
exam is unchanged, then immobilization • If repeat radiographs are negative and child is
should continue with thumb spica cast, and pain-free, then likelihood of fracture is low,
MRI should be obtained and immobilization can be discontinued
13 Orthopedics 499
• If radiographs are positive for fracture (either Treatment

from start or after repeat film), orthopedic • Orthopedic referral. Treatment is according
referral for: to age and displacement. Most cases can be
–– Nondisplaced fracture: Thumb spica cast treated by closed reduction and casting; some
–– Displaced fracture: Surgical intervention cases will require internal fixation
Tibial Shaft Fracture Toddler Fracture

• Pain, swelling, and deformity of the affected • A spiral tibial shaft fracture that occurs in
extremity toddlers due to twisting trauma
• Can be complicated by compartment syn- • It is a relatively common injury in children
drome (pain increases after application of less than 4 years old
cast)
• Radiograph will show the fracture Diagnosis
(Fig. 13.45). • The parents recall no or minimal trauma in
most cases
• Limping or inability to bear weight on the
a b affected side. Minimal swelling and no
deformity
• External rotation of foot will cause pain and
discomfort to the child
• Radiographs will show spiral nondisplaced
fracture of the distal tibia (Fig. 13.46)
• Sometimes, primary radiograph is negative,
but the follow-up radiograph will show the
evidence of healing (periosteal new bone for-
mation and callus at the fracture site)
Management
• Orthopedic referral (treatment is above-knee
cast for 2–3 weeks with repeat radiographs
after cast removal)
Ankle Fractures
Background
• The mechanism of the fracture is twisting
injury to the ankles
Fig. 13.45 Tibial shaft fracture. A 14-year-old boy fell • Can lead to disruption of the syndesmotic
down while running down the stairs and had left leg pain and ligaments between the tibia and fibula (syn-
swelling. Radiographs (a, b) show mid-shaft tibia fracture, desmotic injury) (Fig. 13.47)
which was managed nonsurgically with casting
• Nondisplaced distal fibular physeal injury

(Salter–Harris type I): Common injury in
children due to twisting injury of the ankle,
equivalent to ankle sprain
Diagnosis (Table 13.4)
• Pain, swelling, and deformity of the affected
ankle
• Inability to bear weight on the affected side
Treatment
• Orthopedic referral. Displaced fracture or
fracture with widening of the distance
between fibula and tibia will require surgical
fixation (see Fig. 13.47)
• Nondisplaced distal fibular physeal injury
can be treated by immediate weight bearing
in a controlled ankle motion (CAM) walking
boot, boot, or cast
Compartment Syndrome
Background
• Elevation of the interstitial pressure in a
closed osteofascial compartment that results
in microvascular compromise
• Compartment syndrome should be suspected
in children involved in accidents with high-
energy trauma to the extremities
• More common with fractures of the lower leg
and forearm
Diagnosis
• Tense non-compressible swelling of the
affected compartment
• Increase in the narcotic requirements to keep
Fig. 13.46 Toddler fracture. A 3-year-old boy presented the child comfortable is an early sign of
with his parents because of 2 days’ refusal to walk. On exam, increased compartment pressure
there was tenderness of the lower leg with pain on external
rotation of the tibia. Radiograph shows spiral nondisplaced
fracture of the lower end of the tibia
13 Orthopedics 501
a b c
Fig. 13.47 Ankle fracture. A 16-year-old had left ankle medial joint space (open arrow). (c) Surgery was done for
injury while playing soccer. (a, b) Radiographs showed frac- fixation of the fracture with plates and screws (notice reduc-
ture distal fibula (arrows) with widening of the distance tion of the distance between tibia and fibula and narrowing of
between tibia and fibula (dotted line) and widening of the the medial joint space)
Table 13.4 Clinical differentiation between ankle sprain Treatment

and ankle fracture • Once compartment syndrome is suspected,
Ankle sprain Ankle fracture cast and splints should be removed or split
Depending on the degree of Cannot bear weight immediately
injury, most cases can bear immediately after injury
slight weight
• The affected extremity should be elevated to
No bony tenderness Bony tenderness/ the level of the heart (elevating the extremity
crepitation above the level of the heart will decrease tis-
Palpate medial and sue perfusion)
lateral malleolus, base of • Urgent orthopedic consult: Definitive treat-
the fifth metatarsal,
mid-foot bone
ment of compartment syndrome consists of
Maximal point of tenderness in Maximal point of wide prompt release of the affected compart-
anterior talofibular ligament tenderness in the affected ments (fasciotomy)
and/or calcaneofibular ligament bone
areas
Painful and swollen Painful and swollen
RADIAL HEAD SUBLUXATION
• Severe excruciating pain with passive stretch
of the distal joints (toes or fingers) ursemaid Elbow (Pulled Elbow)
N
• Paresthesias, pulselessness, and paralysis are
late findings, and the absence of these signs Background
does not rule out this diagnosis • Subluxation of the radial head from the annu-
• Compartment pressure can be measured using lar ligament
pressure needle. Pressure more than 30 mmHg • Common condition in young children aged
suggests that patient may have compartment 1–4 years
syndrome
Diagnosis
• A child with no obvious history of trauma
will suddenly refuse to use his/her arm.
• Common scenarios include the following: A
toddler held by his or her hand, then the child
and adult move in opposite directions
• Radiograph will be negative
Treatment
• Reduction maneuvers: One hand supports the
elbow and the other hand applies axial com-
pression at the wrist while fully supinating
the forearm and then flexing the elbow
• A click or snap can usually be felt at the radial
Fig. 13.48 Radiograph of a 6-year-old boy who had sudden
head with successful reduction. left shoulder pain while playing shows proximal humeral
• Most children will show immediate return of fracture (black arrow). Notice the simple bone cyst that
function 15–30 min after the reduction affected the proximal humerus (white arrows)
Treatment
BONE TUMORS/TUMORLIKE • Orthopedic referral for symptomatic lesion.
Treatment can be by surgical debridement or
CONDITIONS
steroid injection. Nonsymptomatic lesions
discovered accidentally do not need inter-
Unicameral Cyst
vention. For lesions with associated patho-
Background logical fractures, management of the fracture
• The unicameral bone cyst is not a true neo- should be done first, as the lesion may heal
plasm; unknown pathogenesis during the healing process of the secondary
• Age usually ranges between 5 and 15 years. fracture
More in males
• Most commonly found in the proximal
humerus and upper femur
Aneurysmal Bone Cyst (ABC)
• Most cases are asymptomatic • The ABC is an expansile cystic lesion
• Pathological fracture: Pain after minor trauma • The true etiology is unknown; however, most
due to pathological fracture of the affected experts believe that ABCs are the result of a
bone vascular malformation within the bone
• Occasionally, accidentally discovered in • The gross appearance of the ABC is that of a
radiograph done for another reason blood-soaked sponge. A thin subperiosteal
• Radiographs: A well-defined lytic lesion situ- shell of new bone surrounds the structure and
ated in the intramedullary metaphyseal region contains cystic blood-filled cavities
immediately adjacent to the physis. A cortical
Diagnosis
piece of bone can be seen in the middle of the
• Pain and swelling over the affected bone
lesion (fallen leaf sign) and is pathognomonic
• Pathologic fracture
of a simple bone cyst (Fig. 13.48)
13 Orthopedics 503
• Radiographs: Soap-bubble appearance with O steochondroma

an eggshell-appearing bony rim surrounding
the lesion Background
• The most common benign bone tumor
Treatment • Osteochondromas can be solitary or multiple.
• Orthopedic referral: The lesion can be treated Hereditary multiple exostoses (HME) is an
with intralesional curettage and bone grafting autosomal dominant syndrome characterized
or wide excision of the lesion by multiple osteochondromas affecting dif-
ferent bone
• Pathology: The medullary canal of the osteo-
Osteoid Osteoma chondroma and the host bone are in continu-
ity. It is most commonly found around the
Background
knee and the proximal humerus in the metaph-
• Osteoid osteoma is a benign tumor consisting
yseal areas (Fig. 13.49)
of a well-demarcated bone-forming lesion
called a nidus, surrounded by a radio-dense, Diagnosis
reactive zone of host bone • Osteochondromas are commonly diagnosed
• More common in males, in second and third incidentally, based on a radiograph obtained
decades for another reason
• Usually affects the diaphysis of long bones • The second most common presenting symp-
tom is a mass
Diagnosis
• Pain that increases at night and is relieved by Treatment
aspirin and other NSAID, not relieved by rest • Asymptomatic lesions can be safely observed.
• Radiographs: Small defect less than 1.5 cm in No orthopedic referral is needed for asymp-
diameter and is associated with a variable degree tomatic lesions
of cortical and endosteal sclerosis. In most cases, • If painful or multiple: Orthopedic referral
the defect cannot be seen, and surrounding scle-
rosis is the only finding in the radiograph. CT
will more clearly show the lesion and the nidus Osteosarcoma
Treatment Background
• Orthopedic referral for excision of the lesion. • Osteosarcoma is a primary malignant tumor
CT-guided percutaneous radiofrequency of bone with malignant osteoid formation
ablation of the nidus can also lead to com- arising from bone- forming mesenchymal
plete resolution of symptoms cells
Fig. 13.49 A 15-year- a b c

old boy presented with
mass in the posterolateral
part of the left gluteal
area (arrow). Radiograph
showed osteochondroma
(pedunculated). Magnetic
resonance imaging (MRI)
assessed the thickness of
the cartilaginous cap
(4 mm)
a b Treatment
• Requires cooperation between the orthopedic
surgeon and the oncologist
• Treatment and prognosis depend on the sub-
type and grade of the tumor
• Treatment is usually by wide resection with
reconstruction and adjuvant chemotherapy.
Osteosarcomas do not respond to radiation
therapy
Ewing Sarcoma
Background
Fig. 13.50 Osteosarcoma. Anteroposterior (a) and lateral • A primary malignant bone tumor (round
(b) views of right knee showing signs of osteosarcoma:
cell sarcoma) that arises from the medul-
Sunray appearance (arrow), Codman’s triangle (arrow head),
cortical erosion (line), and soft tissue shadow (dotted line) lary tissue, mostly from the lining cells of
the medullary blood or lymphatic
• The strongest genetic predisposition to osteo- channels
sarcoma is found in patients with hereditary • The most common primary malignant tumor
retinoblastoma. In hereditary retinoblastoma, in patients less than 10 years old
mutations of the RB1 gene are common • More common in male
• Osteosarcoma is the most common primary • Occurs in diaphysis of the long bones
malignant bone tumor under the age 20 years
• Occurs in the metaphysis of long bones, com- Diagnosis
monly found around the knee • Pain and tenderness over the involved area
• Swelling (slowly growing, warm, tender,
Diagnosis ill-defined, hard, diaphyseal)
• Pain is the first and most common symptom; • Fever, anorexia, headache, and malaise
it is usually constant and severe may be the presenting symptoms (clinical
• Swelling (usually pain precedes swelling) presentation may be similar to
• Pathological fracture osteomyelitis)
• Radiographs: Skeletally immature patient • Radiographs: Medullary destruction, soft tis-
with an osteolytic lesion that is metaphyseal, sue mass with reactive new bone formation.
eccentric, and having ill-defined edges with Multiple layers of elevated periosteum
new bone formation and erosion of the cortex (onion-peel appearance) (Fig. 13.51)
(Fig. 13.50)
• CT: Better assessment of bone destruction Treatment
• MRI: Better assessment of soft tissue mass, • Orthopedic referral: Chemotherapy, radio-
invasion of nearby neurovascular bundle, and therapy, and surgical excision of the tumor
satellite lesions (skip lesions in the same bone)
13 Orthopedics 505
joint destruction may occur if urgent surgical

drainage and irrigation are not performed.
• Congenital muscular torticollis can be associ-
ated with congenital dysplasia of the hip and/
or metatarsus adductus.
• Most cases of intoeing represent normal
development and do not need orthopedic
referral.
• Tibial torsion usually improves by the age of
3 years, and femoral anteversion usually
improves by the age of 8 years.
• If the foot deformity in cases of metatarsus
adductus is flexible (the forefoot can be
abducted), stretching exercises are sufficient.
Fig. 13.51 Ewing sarcoma. An 8-year-old boy with left
forearm pain and swelling. Radiograph showed Ewing sar-
• Flexible flatfoot is a normal finding and does
coma of the ulnar diaphysis. Notice the location of the lesion not require treatment or referral.
(diaphysis) and the periosteal new bone formation • The longitudinal foot arch does not develop
until the age of 4 years.
PEARLS AND PITFALLS
References
• Polyhydramnios, short umbilical cord, and
fetal akinesia are associated with 1. Abdelgawad A, Naga O. Pediatric orthope-
arthrogryposis. dics: a handbook for primary care physicians.
• DDH risk increases in firstborn, female, New York: Springer Science+Business Media;
breech presentation, and positive family his- 2014.

2.
Pediatric Orthopaedic Society of North
tory for DDH.
America, International Hip Dysplasia Institute,
• Hip ultrasound screening for DDH before
American Academy of Orthopaedic Surgeons,
6 weeks of age may be overly sensitive and
United States Bone and Joint Initiative,
result in overtreatment.
Shriners Hospitals for Children. Position
• Physical examination is the most important statement: swaddling and developmental hip
diagnostic tool in diagnosing DDH in neonates. dysplasia. Rosemont: Pediatric Orthopaedic
• In any child with unexplained knee pain, e.g., Society of North America; 2015. www.aaos.
no history of knee trauma and normal knee org/uploadedFiles/PreProduction/About/
examination, the hip joint must be considered Opinion_Statements/position/1186%20
as a possible source of pain or limp. Swaddling%20and%20Developmental%20
• Septic arthritis is a surgical emergency and Hip%20Dysplasia%281%29.pdf. Accessed 5
should be immediately referred to a pediatric Oct 2018.
orthopedic surgeon. A rapid and progressive
3. Pacana MJ, Hennrikus WL, Slough J, Curtin ence guide. 2nd ed. Elk Grove Village: American
W. Ultrasound examination for infants born Academy of Pediatrics; 2014a. p. 151–60.
breech by elective cesarean section with a nor- Sarwark JF., LaBella CR. Congenital anomalies of
mal hip exam for instability. J Pediatr Orthop. the upper extremities. In: Pediatric orthopedics
2017;37(1):e15–8. and sports injuries: a quick reference guide. 2nd
ed. Elk Grove Village: American Academy of
Pediatrics; 2014b p. 247–59.
Suggested Reading Sarwark JF., LaBella CR. Leg-length discrepancy.
In: Pediatric orthopedics and sports injuries:
Abdelgawad A, Kanlic E. Orthopedic trauma. a quick reference guide. 2nd ed. Elk Grove
In: Abdelgawad A, Naga O, editors. Pediatric Village, IL: American Academy of Pediatrics.
orthopedics. A handbook for primary care 2014c. p. 561–7.
physicians. New York: Springer; 2014. Sarwark JF., LaBella CR. Torticollis. In: Pediatric
p. 409–83. orthopedics and sports injuries: a quick refer-
Abdelgawad A, Naga O. Pediatric spine. In: ence guide. 2nd ed. Elk Grove Village: American
Abdelgawad A, Naga O, editors. Pediatric Academy of Pediatrics. 2014d p. 169–77.
orthopedics. A handbook for primary care phy- Sponseller PD. Bone, joint, and muscle problems.
sicians. New York: Springer; 2014. p. 503–43. In: McMillan JA, Feigin RD, DeAngelis C,
Sarwark JF., LaBella CR. Back pain; general Jones MD, editors. Oski’s pediatrics: principles
approach and differential diagnosis. In: Pediatric and practice. 4th ed. Philadelphia: Lippincott
orthopedics and sports injuries: a quick refer- Williams and Wilkins; 2006. p. 2470–504.
Sports Medicine
14
Daniel Murphy
PRE-PARTICIPATION Evaluation
• Evaluation must be completed at a minimum
EVALUATION of 6 weeks prior to starting preseason
Background practice
• Preventative tool to ensure the safety of the • Injuries sustained during the previous year
athlete should be discussed with the examiner to
• Screen for illness and past injuries, to identify ensure proper recovery
athletes who may be at risk or may develop • At the collegiate level, pre-participation
complications based on lifestyle choices and physical exam should occur yearly
goals • At the secondary school level, each state has
• Promote the health and wellness of the their own required timeline; therefore, par-
athlete ents should inquire the school about neces-
sary requirements
Screening tests • Completing a medical history in high school
• No routine tests are required for pre-partici- and collegiate athletes will identify 65–77%
pation clearance of all medical conditions
• Routine electrocardiogram (ECG) screening • All positive responses should be further
remains controversial and has not been imple- investigated and questioned by the screening
mented as a standard protocol physician
• The history and physical will dictate if further • The physical examination plays an integral
diagnostic testing is required part in identifying musculoskeletal, visual, or
cardiovascular disorders
Objective
• Identify life-threatening conditions and/or ill- Clearance
nesses that would increase the risk for injury • The pre-participation physical is not designed
in an athlete to prevent student athletes from competing,
• Expose and educate the athlete to health and but acts as a safeguard to identify conditions
wellness and promote self-awareness that may need further evaluation
• Discuss issues that may be concerning to the • The individual sport needs to be taken into
athlete consideration when completing the
examination
D. Murphy (*) • Cardiovascular demands are extremely
Department of Family and Community Medicine, Paul L. Foster
School of Medicine, Texas Tech University Health Center, important when providing final clearance
El Paso, TX, USA
e-mail: Daniel.murphy@ttuhsc.edu

508 D. Murphy
• Static versus dynamic exercises must be taken Fever

into consideration, with static exercises • No participation in sports during febrile illness
increasing pressure load and dynamic increas- • Athletes with systemic symptoms including
ing volume load fever and myalgias should refrain from physi-
• If full and unrestricted participation is not cal activity for at least 7–14 days
granted to the student athlete, it is imperative • Individuals with infectious mononucleosis
that the athlete and guardian/parents are are restricted from physical activity for a
aware of the restrictions and how they affect minimum period of 3 weeks
the level of participation
• The level of participation may change based Syncope and chest pain
on new or changing medical conditions • A personal history of syncope, near-syncope,
chest pain, palpitations, or excessive short-
ness of breath or fatigue with exertion should
Medical Conditions Affecting Sports prompt a more thorough evaluation, either by
Participation (Table 14.1) the primary clinician or a cardiologist
Table 14.1 Medical conditions affecting sports participations

Medical
condition Participation Comments
Fever No Increased risk of heat illness
Diarrhea, No Increased risk of dehydration
infectious
Seizure Yes Excludes swimming, diving, archery, or other sports that impose risk to others
Atlantoaxial Yes Needs evaluation to assess risk of spinal cord injury during sport
instability
History of heat Yes Conditioning, sufficient acclimatization, hydration, salt intake to prevent recurrence
illness
Enlarged spleen Yes Not in acute cases because of risk of rupture; if chronically enlarged, individual
assessment is required
Heart murmur Yes If innocent murmur, otherwise needs cardiology evaluation
Hypertrophic No Cardiology consultation is recommended
cardiomyopathy
Functionally Yes Best corrected eye is 20/40 or worse, needs individual assessment and eye protection
one-eyed athlete
Pregnancy Yes Scuba diving and sports with high risk of falling or risk of altitude sickness should be
avoided
One ovary Yes Risk of ovary injury is minimal
One testicle Yes Protective cup for certain sports
One kidney Yes Protective equipment for most sports especially contact or collision sports
Cerebral palsy Yes Individual assessment according to functional capacity and type of activity
Asthma Yes Albuterol before sports in cases of exercise-induced asthma, not during acute asthma
Upper respiratory Yes Mild cases only; not if having fever
infection
Bleeding disorder Yes Needs individual assessment
Sickle cell trait Yes Cases of sickle cell disease will need individual assessment
Diabetes mellitus Yes Check blood glucose every 30 min during continuous exercise, 15 min after completion
of exercise, and at bedtime
HIV Yes All skin lesions should be covered; if viral load is high, certain sports such as boxing
and wrestling should be avoided
Skin infection Yes Not during contagious period especially in gymnastics, sports using mats, contact
sports
14 Sports Medicine 509
Heart murmur –– If requiring medication daily or several

• If the murmur is innocent (does not indicate times daily, consider adding a controller
heart disease), full participation is permitted. medication such as an inhaled corticoste-
Otherwise, athlete needs evaluation roid with or without a long-acting beta-
agonist or a leukotriene receptor agonist
Cardiac conditions that disqualify an athlete
from sports Diabetes mellitus
• Pulmonary vascular disease with cyanosis or • Athletes who have type 1 diabetes mellitus
a hemodynamically significant right-to-left (DM1) are permitted to participate in any
shunt sport without restriction
• Severe pulmonary stenosis (untreated) • At a minimum, athletes who have DM1
• Severe aortic stenosis or regurgitation should measure their blood glucose every
(untreated) 30 min during continuous exercise, 15 min
• Severe mitral stenosis or regurgitation after completion of exercise, and at bedtime
(untreated) • Insulin pumps and rapid-acting insulins have
• Any cardiomyopathy allowed athletes to fine-tune their glycemic
• Vascular Ehlers–Danlos syndrome control much more effectively than in the past
• Coronary anomalies (especially anomalous
coronary origins) HIV infection
• Catecholaminergic polymorphic ventricular • Because of the apparent minimal risk to oth-
tachycardia ers, all sports may be played as athlete’s state
• Acute pericarditis of health allows
• Acute myocarditis • For all athletes, skin lesions should be cov-
• Acute Kawasaki disease (less than 8 weeks) ered properly
• If viral load is detectable, then athletes should
Cardiac conditions for which athletes require be advised to avoid high-contact sports such
cardiologist consultation as wrestling and boxing
• Marfan syndrome
• Mitral valve prolapse Seizure disorder, well-controlled
• Dysrhythmia (irregular heart rhythm) • Risk of seizure during participation is
• Long-QT syndrome minimal
• Wolff–Parkinson–White syndrome • Participation in water activities must be con-
• Advanced heart block ducted under direct supervision at all times
• Kawasaki disease (coronary artery vasculitis)
of 8 weeks or more Seizure disorder, poorly controlled
• Pulmonary hypertension • Athlete needs individual assessment for colli-
• Anthracycline use sion, contact, or limited-contact sports
• The following noncontact sports should be
Exercise-induced bronchoconstriction avoided:
• Non-pharmacologic treatment includes: –– Archery, riflery, swimming, weight lifting,
–– Warm-up exercise powerlifting, strength training, and sports
–– Using a face mask/scarf during exercise involving heights; in such sports, occur-
• Pharmacologic treatment includes: rence of a seizure during activity may pose
–– Short-acting beta-agonists (SABA) to treat a risk to self or others
symptoms –– Physical activity should be promoted as
–– To prevent symptoms, may use SABA long as there is not a significant risk to the
5–20 min before exercise individual
510 D. Murphy
Cerebral palsy • Tinea capitis requires a minimum of 2 weeks

• Athlete needs evaluation to assess functional of treatment
capacity to perform sports-specific activity
• Functional aerobic and strength training that Herpes simplex
increases muscle size and strength • Free of systemic symptoms
• Addition of anaerobic training to progressive • No new lesions for at least 72 h
resistance strengthening leads to improved • No moist lesions
functional capacity • All lesions must be covered with a firm,
adherent crust
Down syndrome (DS) • Minimum of 120 h of systemic treatment
• Instability of the cervical spine (primarily • Active lesions cannot be covered to allow for
atlantoaxial instability, but also occipitoatlan- participation
tal instability) has been reported in up to 30%
of patients with DS Molluscum contagiosum
• Check for gait disturbance, neck movements, • Lesions must be removed or treated with
tendon reflexes, and plantar responses. curettage
• The Special Olympics organization requires • Localized lesions may be covered with a dress-
radiographic evaluation of the cervical spine ing followed by underwrap and stretch tape
before sports participation
• DS patients should be prohibited from par- Furuncle/carbuncles/folliculitis/impetigo/
ticipating in collision sports regardless of the cellulitis
radiographic appearance of their spines. • No new lesions for minimum of 48 h
However, no other limitations need be • Minimum of 72 h of treatment
imposed for patients who have normal cervi- • No moist, exudative, or draining lesions
cal spine radiographs • Active lesions cannot be covered to allow for
• Special Olympics considers diving, gymnas- participation
tics, butterfly stroke, high jumping, soccer, • Prevention
and pentathlon to be “neck-stressing.” –– Wash hands with soap and water
Athletes with DS and cervical instability may –– Avoid whirlpools or common tubs
use a cervical collar, but this practice does not –– Avoid sharing towels and razors
change their sport restriction –– Clean facilities daily
• DS is associated with other abnormalities that –– Treat and cover skin lesions
may influence sports participation, such as
cardiac abnormalities (septum defects, in par- Eyes
ticular), cataracts, diabetes, thyroid disease, • Protective eyewear is recommended in all
hip and patellar instability, and foot sports involving risk for eye injury
abnormalities • Lenses made of polycarbonate or CR-39 are
recommended for protection
Skin diseases • Strap is necessary to secure the protective
• Open wounds should be cleaned and covered eyewear in place
for practice and play to reduce the risk of • Visual acuity of 20/40 or better is considered
blood-borne pathogen transmission to provide good vision
• Visual acuity of less than 20/40 in one eye is
Tinea corporis considered functionally one-eyed
• Tinea corporis requires a minimum of 72 h of • Protective eyewear is required in all athletes
topical treatment with antifungal cream considered functionally one-eyed
• Lesions must be covered with a gas-perme- • Visual acuity must be checked at each well-
able dressing child visit
Eating disorders • 48% of those patients presenting to the emer-

• Restriction from practice and competition gency room are youth and adolescent indi-
until medically stable and has recovered from viduals playing football
the eating disorder
Risk factors
Sickle cell disease and trait • Hot weather
• Regular, non-stressful exercise • Humidity
• Gradual increase in physical activity over weeks • Poor fitness
• Plenty of fluids before, during, and after • Elevated body mass index (BMI)
exercise • Elderly
• Avoid collision, endurance, and high-inten- • Medications
sity sports
• Rest when tired Clinical presentation
• Adequate hydration • Cramps
• Focus on sports that requires focus and skill, • Dehydration
not endurance • Fatigue
• Adequate oxygenation • Elevated body temperature
• Counseling to prevent sickle cell crisis • Diaphoresis
• Nausea
Obesity • Weakness
• Discourage sedentary lifestyle • Altered mental status
• Promote physical activity • Dizziness
• Nutritional education • Delirium
• Restrict high-sugar foods
• Restrict time spent watching TV and playing Diagnosis
video games • Heat Exhaustion
–– Rectal temperature less than 104 °F
Solitary kidney • Heatstroke
• A qualified yes for participation in adoles- –– Core rectal temperature ≥ 104 °F
cents with only one kidney –– Multi-organ system failure
• Individual player assessment must be con-
ducted to determine if additional protective Treatment
equipment is needed • Heat Exhaustion
• Protective equipment may reduce the risk of –– Lay patient in supine position in a shaded
injury sufficiently to allow participation in area
most sports – – Cooling
–– Oral fluid replacement
–– Rapid cooling
Heat Illness –– Ice packs in neck, axilla, and groin
–– Submersion in ice water bath
Background • Heatstroke
• Exertional heatstroke is a potentially life- –– Early recognition with rapid and immedi-
threatening condition that accounts for ~2% ate cooling in ice water bath
of all sports-related deaths –– Oral rehydration if possible
• Patients under the age of 20 account for a –– Maintain airway, breathing, and
majority of exertional heat illnesses present- circulation
ing to the emergency room –– Transport to nearest emergency facility
512 D. Murphy
INJURY PREVENTION –– Cycling, football, baseball and softball,

basketball, skateboards/scooters, water
onditioning (Role of Conditioning
C sports, soccer, trampolines
in Preventing Injuries in Athletes) • Prevention
–– Helmets can significantly reduce the risk
Background of severe brain injuries
• Interventions based on exercise are effective
in treating and preventing injuries
• Most interventions used to prevent injuries Mouth
include stretching, core stability, and
• Use of a mouthguard during sports activities
plyometrics
decreases oral injuries, including tooth avul-
• Injuries are reduced by 40% in those who
sions, tooth fractures, and lacerations
implement prevention programs
• Custom mouthguards made for an individ-
Treatment ual by a dental health professional may fit
• Physical activity-based conditioning, com- better and be more comfortable than less
pared to just stretching, reduces injuries by expensive “boil and bite” or off-the-shelf
35–50% mouthguards.
• Strength-training exercise should incorporate • Professionally fitted mouthguards have not
concentric and eccentric exercises consistently been shown to decrease oral
injury rates compared with “boil and bite” or
off-the-shelf mouthguards.
Role of Rehabilitation of Current • Although mouthguards decrease the risk of
Injuries to Prevent Further Injuries dental injury, they do not provide protection
against sports concussions
Background
• Loss of motion typically occurs following a
sports injury or surgery Neck Injury
• Rehabilitation is key to successful results fol-
• Over half of catastrophic injuries in sports are
lowing injury or surgery
cervical spine injuries.
• A team approach with a treatment plan is
• Cervical spine injuries have been reported in
essential for appropriate recovery
most contact sports, including football,
Treatment hockey, rugby, and wrestling, as well as in
• Early motion and mobility following injury several noncontact sports, such as skiing,
• Rehabilitation should begin immediately fol- track and field, diving, surfing, powerlifting,
lowing the injury or surgery and equestrian events
• Establish milestones and goals for • Cervical spine injuries are estimated to occur
rehabilitation in 10–15% of all football players, most com-
• Create a treatment plan that is effective monly in linemen and defensive players.
• Full immobilization on a backboard is
required to stabilize the neck
Head Injuries • When immobilizing the neck, avoid move-
ment and maintain proper alignment of the
• Sports in which a head injury most commonly cervical vertebrae. This usually can be done
occurs: with the helmet and other protective gear
(e.g., shoulder pads) in place, and such equip- cussion, but currently there is no evidence to
ment should not be removed support this
• In the football setting, the athlete should be • Currently, there is no imaging modality avail-
immobilized with the pads and helmet both able that identifies any structural abnormali-
on or both off ties within the central nervous system
• When direct access to the face is required, the
face mask may be removed from the helmet Treatment
with a screwdriver or cutting tool • The Concussion in Sports Group has identi-
fied 11 steps necessary for concussion man-
agement. These include:
SPORTS-RELATED INJURIES –– Recognize
◦◦ It is important to determine if the symp-
Mild Traumatic Brain Injury toms present are not the result of drugs,
(Concussion) alcohol, medication, cervical injuries, or
vestibular dysfunction
Background –– Remove
• Annually, there are 300,000 sports-related ◦◦ Athlete should be removed and evalu-
concussions among high school and colle- ated by a health professional when a
giate athletes concussion is suspected
• Sports is the second leading cause of concus- ◦ ◦ Athletes may not return to play during
sions in individuals aged 15–24 the same game
• Biomechanical forces directly or indirectly – – Reevaluate
applied to the brain ◦◦ Individual should be reevaluated for
• Inappropriately treated concussion may lead sleep/wake disturbance, ocular function,
to second-impact syndrome, causing uncon- and vestibular function
trolled cerebral edema ◦◦ Neuropsychiatric testing contributes
clinical value, but no evidence exists
Clinical presentation suggesting that outcomes are different
• Headache when neuropsychiatric testing is
• Dizziness completed
• Blurred vision ◦◦ Neuropsychiatric assessment is not
• Retrograde or anterograde amnesia needed for all athletes following a
• Emotional lability sports-related concussion
• Nausea and/or vomiting –– Rest
• Confusion ◦◦ Complete rest is recommended during
• Memory loss the first 24–48 h following the
• Poor concentration concussion
◦◦ Following this brief period, individuals
Diagnosis may be encouraged to increase their
• History and physical level of activity gradually
• The diagnosis of a concussion is a clinical ◦◦ The level and intensity must not induce
decision based on presentation and an incit- or worsen symptoms
ing event that may have led to forces trans- ◦◦ Prolonged rest may delay recovery
mitted to the brain ◦◦ The overall goal is to increase physical
• Neuropsychological testing is utilized to activity without inducing symptoms
identify and monitor the progression of a con- after a brief period of rest
514 D. Murphy
–– Rehabilitation ◦◦ Athletes should wait a minimum of

◦◦ Symptoms lasting longer than 10 days before returning to contact
10–14 days should incorporate psycho- sports
logical, cervical, and vestibular –– Reconsider
therapy ◦◦ Prior to returning the athlete to sports,
◦◦ Gradual increase in physical activity they must return to full academics
below the level of symptom induction ◦◦ Prior to returning to academics, a com-
–– Refer plete rest period of 24–48 h must be
◦◦ Symptoms lasting longer than 4 weeks implemented
in children should have a multidisci- ◦◦ Before returning to academics, the ath-
plinary approach with specialists trained lete must perform daily activities at
in concussion management home that do not give the individual
◦◦ Targeted aerobic exercise program symptoms
should be implemented in individuals ◦◦ Thereafter, the athlete may return to aca-
with autonomic instability or demics part-time and, if tolerated, tran-
deconditioning sition to full time
◦◦ Physical therapy should initially be –– Residual effects and sequelae
directed toward vestibular- and cervical- ◦◦ Various studies have shown that repeated
related symptoms concussions may lead to depression and
◦◦ Currently, there are no medications rec- cognitive impairment along with chronic
ommended for the treatment of sports- traumatic encephalopathy
related concussion ◦◦ Further research is needed examining
–– Recover the cause and effect relationship
◦◦ Currently, there is no evidence outlining –– Risk reduction
the length of time for recovery ◦◦ Mixed results are evident with the use of
◦◦ Current research is investigating various a mouthguard
forms of imaging and blood markers to ◦◦ Vision training may reduce the preva-
determine the presence and length of lence of concussions
time for recovery ◦◦ Revisioning policies and rules of com-
◦◦ It is difficult to determine how long the petition have had an effect in reducing
symptoms will last in an individual with the number of concussions
a sports-related concussion • The Concussion in Sports Group has recently
–– Return to sport outlined six-step recommendations for return
◦◦ The first step of the return-to-play proto- to sport following a concussion:
col has been modified and recommends –– Limited activity that does not provoke
that an initial 24–48 h of physical and symptoms
cognitive rest be completed before the –– Light aerobic activity
return-to-sport protocol may begin –– Sport-specific exercise
◦◦ Step one of the protocol recommends –– Noncontact drills
symptom-limited activity that does not –– Full-contact practice
provoke symptoms –– Return to full play
◦◦ Most repeat concussions occur during • Before the return-to-play protocol can be ini-
the first 10 days following the initial tiated, the athlete must return to full academ-
concussion ics without limitations/restrictions.
nterior Shoulder (Glenohumeral)

A • Posterior shoulder dislocation may not be
Dislocation obvious on AP view. Axillary and trans-
scapular views are necessary to show the
Background deformity
• The shoulder joint is one of the most mobile
joints in the body, but this flexibility comes Treatment
at the expense of stability, making it the • Closed reduction should be accomplished as
most common major joint to become soon as possible before significant muscle
dislocated spasm and pain development
• More than 90% of all dislocations are anterior • Arm should be immobilized for about 2 weeks
glenohumeral dislocation (the humeral head in a sling, then gradual range of motion
is anterior to the glenoid) (ROM) exercises, and strengthening exer-
• Posterior glenohumeral dislocation is less cises as tolerated
than 10% of all traumatic shoulder disloca- • Return to play: Athlete must regain full ROM
tions and commonly occurs as a result of and strength before return to play
seizures • Indications for surgical intervention:
Recurrent shoulder dislocations or associated
Diagnosis large bony lesion
• Anterior shoulder dislocation most com-
monly occurs after a fall on outstretched hand
with arm abducted and externally rotated Acromioclavicular (AC) Dislocation
• Examination will show obvious deformity—
Background
prominent acromion; humeral head may be
• Separation of the joint between the lateral end
seen anteriorly with palpable defect inferior
of the clavicle and acromion. Occurs after
to acromion
direct fall onto the point of the shoulder
• The patient holds affected arm in abducted
and externally rotated position
• Radiographs (anteroposterior [AP], axillary, Diagnosis
and trans-scapular Y view) will show empty • Swelling and tenderness over the affected AC
glenoid and abnormal position of the humeral joint
head • Deformity at the AC joint (see Fig. 14.1b)
Fig. 14.1 A 13-year-old boy

who fell in football practice on
a b
his left shoulder. (a) Radiograph
taken at the time of injury shows
separation between the clavicle
and acromion (arrow). (b)
Obvious deformity on the left
shoulder (arrow)
516 D. Murphy
• Limited ROM of the shoulder due to pain Treatment

• Passive adduction of the arm across the body • Nonoperative management due to high
produces pain at the AC joint remodeling potential
• Radiographs with AP, axillary, and Zanca • Cessation from throwing
views (AP with 10° cephalic tilt focused on • Strengthening of the rotator cuff, scapulotho-
AC joint) will demonstrate widening and/or racic, and core musculature
displacement of AC joint (see Fig. 14.1a) • An average rest period of 3 months is needed
to return to play without deficits
Treatment
• Mild displacement: Sling immobilization
with early ROM Little Leaguer’s Elbow
• Marked displacement: Orthopedic referral for Clinical presentation
possible surgical intervention • Pain and swelling over medial elbow
• Decreased ROM with extension
Little Leaguer’s Shoulder and Elbow Diagnosis

• History and physical
Background • 85% of x-rays will appear normal
• 25% to 28% of young pitchers aged 9–12 were
Treatment
found to complain of elbow pain and 32–35%
• Abstinence from throwing
complained of shoulder pain
• Initial immobilization in an elbow brace
• Youth pitchers between the ages of 9–14 have
• Open reduction and internal fixation for more
a 5% risk of severe injury
severe cases involving a fracture
• During the cocking and acceleration phase of
• Return to play: 12 weeks of rest required if
pitching, the ulnar collateral ligament pro-
nonoperative treatment is needed; 7–8 months
vides 55% of valgus stability
of rest required if operative treatment is
• Little Leaguer’s shoulder is the result of repeti-
needed
tive stress to the proximal humeral growth plate
• Little Leaguer’s elbow is the result of repeti-
tive stress to the medial epicondylar plate
Deep Hematoma of Thigh
Little Leaguer’s Shoulder Background

Clinical Presentation • Result of blunt trauma to the thigh during ath-
• Typically occurs in males between the age of letic competition
13–16 during periods of rapid growth • Thigh contusions are common injuries in
• Pain athletes
• Tenderness • Rarely causes thigh compartment syndrome
• Widened physis of proximal humerus
Risk Factors
Diagnosis • Blunt trauma
• History and physical • Athletic competition
• X-ray of shoulder in both anterior and poste- • Use of anticoagulants
rior views with internal and external rotation

• Anterior thigh pain • History and physical
• Swelling • X-ray if patient meets Ottawa Ankle Rules
• Decreased knee flexion criteria
• MRI if ligamentous, osteochondral, syndes-
Diagnosis motic, or occult fracture is suspected
• Clinical suspicion is best diagnostic tool to
identify thigh compartment syndrome Treatment
• Chest x-ray • RICE
• CT • Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Thigh compartment pressure • Functional support and exercise therapy
• Neuromuscular and proprioceptive exercise
Treatment • Surgery for chronic instability not responsive
• Rest to conservative treatment
• Ice • Acupuncture and vibration therapy
• Elevation
• If thigh compartment syndrome is suspected,
immediate surgical decompression is required OVERUSE INJURIES
Osgood–Schlatter Syndrome
Ankle Sprain
Background
Background • Approximately 30 million children partici-
• 40% of all traumatic ankle injuries occur dur- pate in sporting activities
ing sports • Limb length increases by a factor of 1.4
• Only 50% of individuals who suffer a lateral between the ages of 6 and 14 years, with limb
ankle sprain seek medical attention mass increasing by a factor of 3, leading to
• Chronic ankle instability may result from a musculoskeletal imbalance
lateral ankle sprain • Osgood–Schlatter syndrome is the most com-
mon cause of anterior knee pain in adolescents
Risk factors
• During growth, the quadriceps become tighter,
• Previous history of ankle sprain
increasing strain on the tibial tubercle
• Inversion deformity of foot
• Female Risk factors
• Limited dorsiflexion • Affects males more than females
• Reduced proprioception • Highly active individuals
• BMI • Mainly seen in running, jumping, kneeling,
and stair-climbing activities
• Lateral ankle pain Clinical presentation
• Swelling • Anterior knee pain
• Difficulty with ambulation • Swelling (Fig. 14.2a)
• Ecchymosis • Localized tenderness over the tibial tubercle
518 D. Murphy
Fig. 14.2 Osgood–Schlatter
a b
disease. A14-year-old boy soccer
player with right knee pain. (a)
Examination shows anterior knee
swelling over the tibial tubercle
(arrow). (b) Radiographs of a
patient with Osgood–Schlatter
disease. Wide arrow points to the
enlarged tibial tubercle. Small
arrow points to the small
fragment of calcification and
fragmentation within the patellar
ligament
Diagnosis Diagnosis
• History and physical • History and physical exam
• Radiological signs of Osgood–Schlatter: • Calcification identified on x-ray at the patella–
Enlargement with possible fragmentation of patella tendon junction
the tibial tubercle (not required for diagnosis)
(tibial apophysis; see Fig. 14.2b) Treatment
• Related to level of activity
Treatment • Conservative treatment including reduction
• Conservative treatment in level of activity
• Decreased activity, rest • Anti-inflammatories as needed
• Ice packs for swelling and pain • Icing to reduce swelling
• Anti-inflammatories as needed • Stretching and strengthening of hamstrings
• Symptoms may last up to 2 years before com- and quadriceps
plete resolution • Typically resolves within 8–12 weeks
• Stretching and strengthening hamstring and • More severe cases with osteochondral
quadriceps fragmentation, knee immobilization may be
required
• If fragmentation is present, referral to an
Sinding–Larsen–Johansson Disease
orthopedic surgeon for further evaluation
Background
• Apophysitis of the inferior pole of the patella
• Benign condition atellofemoral Pain
P
• Typically seen in children between the ages
of 10–13 years Background
• Overuse injury affecting the inferior pole of • Accounts for 11–17% of patients presenting
the patella and the patellar tendon with anterior knee pain
• Result of repetitive traction • Typically affects running and jumping ath-
letes who put excessive loads on the knee
Clinical presentation • Females more commonly affected than
• Anterior knee pain localized to the distal pole males
of patella and proximal patella tendon • May be associated with recurrent patellar
• Worsening of pain during running and jumping subluxation (see Chap. 13 Orthopedics)
Risk Factors • Positive patellofemoral grind test

• Sex • Imaging does not identify any structural
• Load-bearing exercises abnormalities
• Weakness
• Overtraining Treatment
• Excessive pronation • Rest, ice, compression, and elevation (RICE)
• Activity modification
• Muscle strengthening and stretching
Clinical Presentation • Correction of biomechanical deficits
• Anterior knee pain • Bracing
• Orthotics if overpronation is present
Diagnosis
• Miserable malalignment syndrome consists
of the following three elements: repatellar Bursitis
P
–– Increased femoral anteversion (Fig. 14.3)
–– External tibial torsion Background
–– Pes planus (flatfoot) • May be caused by an infectious or noninfec-
• Physical examination demonstrating a lateral tious process
“J” sign • Noninfectious process: Recurrent minor inju-
ries associated with overuse (e.g., repeated
kneeling)
• Infectious etiology most commonly caused
by Staphylococcus aureus, which gains
access to bone by direct inoculation (e.g., a
contaminated compound fracture)
Clinical Presentation
• Pain
• Tenderness of the patella to palpation
• Warmth
• Erythema
• Swelling
Diagnosis
• Must differentiate between infectious and
noninfectious
• If infection is suspected, aspiration followed
by Gram stain and culture must be completed
Treatment
• If noninfectious, may be treated conserva-
tively with RICE. May also consider intra-
bursal corticosteroid injection
• Antibiotics in cases of septic bursitis
Fig. 14.3 Miserable malalignment syndrome. A 15-year-
• May require surgical irrigation if not improv-
old girl with 2-year history of knee pain. Patient had excess
femoral anteversion as manifested by her patellae pointing ing with antibiotic administration
inward. Despite the inward position of the patella, her foot is • Bursectomy may be necessary for chronic
still pointing forward due to her external tibial torsion causes
520 D. Murphy
Sever’s Disease ing exercise and other physical activity, as

long as pre-activity hydration status is good
Background • For sports activities lasting 1 h or less, water
• Painful inflammation of the calcaneal apoph- is sufficient for hydration
ysis due to repetitive microtrauma from the • Sports drinks generally contain both electro-
Achilles tendon lytes and sugar and may be more palatable to
• Typically occurs during peak growth spurts children, encouraging hydration with longer
and after starting a new sport or season activity
• Most commonly seen in boys • Energy drinks generally contain high amounts
of caffeine and are not recommended for
young children or adolescents
Risk Factors • Healthy snacks can be offered, along with
• Increase risk in males and those physically water, as an alternative to sports drinks
active
Clinical presentation Female Athlete Triad

• Pain in the heel with activity
Background
Diagnosis • The number of adolescent girls participating
• History and physical in sports has increased in the last few decades
• X-ray to rule out other more serious pathology • Female athlete triad is reported to be preva-
lent in 1–4% of female athletes but is believed
Treatment
to be much higher than this
• Self-limited disease and typically resolves
• Defined as low energy availability with or
once fusion of the apophysis occurs
without disordered eating, menstrual dys-
• Child may continue to participate in activities
function, and low bone mineral density
if pain is not severe
• Heel lifts Risk factors
• NSAIDs • History of depression
• Ice • Eating disorder
• Stretching • Overtraining
• Pressure regarding weight from coaches,
friends, and/or family
MISCELLANEOUS • History of stress fractures
• Nonhealing injuries
Hydration and Rehydration • Osteopenia/osteoporosis
• Encouraging sufficient fluid intake and opti- Diagnosis
mizing hydration status can play an impor- • All three components must be present to make
tant role in maintaining performance and the diagnosis:
reducing the risk of exertional heat illness –– Low energy availability. BMI < 17.5 kg/m^2,
• Generally, 100–250 mL (3–8 oz) every or < 85% expected weight in adolescents
20 min for 9- to 12-year-olds and up to 1.0– –– Amenorrhea
1.5 L (34–50 oz) per hour for adolescent boys –– Bone density consistent with osteopenia or
and girls is enough to minimize sweating- osteoporosis
induced body water deficits sufficiently dur-
Treatment Erythropoiesis-stimulating agents

• Education • Enhance oxygen delivery to active muscles
• Increase energy availability • Enhance aerobic power and physical exercise
• Reduce energy expenditure tolerance
• Weight-bearing exercise • Adverse effects include increased blood vis-
• Resistance training cosity, heart attacks, strokes, deep vein throm-
• Psychotherapy if eating disorder is present bosis, and pulmonary embolism.
• May need a selective serotonin reuptake
inhibitor (SSRI) for comorbid conditions Diagnosis
• Urine drug screen
• Blood analysis for doping
Performance-Enhancing Drugs
Treatment
Background • Education
• 11% of teens have admitted to using growth • Counseling
hormone • Motivational interviewing
• Steroid use in teens has increased from 5% to • Disqualification from competition
7%
• Anabolic steroids, growth hormones, stimu-
lants, and erythropoiesis-stimulating agents are Physical Fitness
all considered performance-enhancing drugs
Background
Clinical presentation • Current guidelines recommend 60 min of
Anabolic steroids moderate- to high-intensity physical activity
• Increased muscle size daily for individuals aged 5–18
• Increased strength • Increased daily screen time is related to
• May cause acne, hepatic dysfunction, sup- negative effects on the cardiovascular
pression of hypothalamus–pituitary–gonadal system
axis, aggression, and premature closure of the • High levels of physical activity, cardiore-
epiphyseal growth plate spiratory fitness, and muscle fitness are
associated with a reduced risk of cardiovas-
Growth hormones cular disease
• Increase in strength, power, aerobic perfor-
mance, and respiratory muscle strength Risk factors
• Adverse effects include hyperglycemia, insu- • Family history of cardiovascular disease and
lin resistance, edema, myalgia, gynecomas- obesity
tia, cardiovascular disease, and intracranial • Increased access to electronics, including
hypertension TV, video games, computers, and cell phones
• Sedentary guardians
Stimulants
• Increase alertness, improved endurance, Treatment
anaerobic performance, and reaction time • Increasing moderate to vigorous physical
• Adverse effects include hypertension, tachy- activity, muscle fitness, and cardiorespiratory
cardia, heart attack, headaches, tremors, fitness to reduce the risk of cardiovascular
insomnia, anxiety, aggression, and psychosis disease
522 D. Murphy
PEARLS AND PITFALLS ing, physical fitness and cardiovascular disease

risk in adolescents: the HELENA study. Int J
• An increasing systolic murmur with Valsalva Cardiol. 2018;254:303–9.
during the pre-participation physical should Bergeron MF, Waller JL, Marinik EL. Voluntary
undergo further evaluation prior to fluid intake and core temperature responses
clearance. in adolescent tennis players: sports bev-
• New onset of tinea, herpes, or molluscum erage versus water. Br J Sports Med.
should restrict athlete from play until mini- 2006;40(5):406–10.
mum duration of treatment is completed. Bernhardt DT, Roberts WO. PPE: preparticipation
• Visual acuity of less than 20/40 is considered physical evaluation. 4th ed. Elk Grove Village:
functionally one-eyed and requires protective American Academy of Pediatrics; 2010.
eyewear. Bratland-Sanda S, Sundgot-Borgen J. Eating dis-
• Individuals with eating disorders or reduced orders in athletes: overview of prevalence, risk
caloric intake should be restricted from fur- factors and recommendations for prevention and
ther practice/competition until caloric intake treatment. Eur J Sport Sci. 2013;13(5):499–508.
matches energy expenditure. Brennan FH, Alent J, Ross MJ. Evaluating the
• Rectal temperature of greater than 104 °F athlete with suspected exercise-induced asthma
requires immediate cooling in an ice water or bronchospasm. Curr Sports Med Rep.
bath followed by further evaluation in the 2018;17(3):85–9.
emergency room. Brown KA, Dewoolkar AV, Baker N, Dodich
• Individuals with a suspected concussion C. The female athlete triad: special consider-
should be removed from competition/practice ations for adolescent female athletes. Transl
and not allowed to return until cleared by a Pediatr. 2017;6(3):144–9.
physician to begin return-to-play protocol. Caggiano S, Cutrera R, Di Marco A, Turchetta
• Little Leaguer’s shoulder and elbow should A. Exercise-induced bronchospasm and
undergo physical therapy to correct throwing allergy. Front Pediatr. 2017;5:131. https://doi.
mechanics. org/10.3389/fped.2017.00131.
• Female athletes with energy deprivation, Capovilla G, Kaufman KR, Perucca E, Moshé SL,
amenorrhea/oligomenorrhea, and decreased Arida RM. Epilepsy, seizures, physical exercise,
bone density should be evaluated for female and sports: a report from the ILAE task force on
athlete triad. sports and epilepsy. Epilepsia. 2016;57(1):6–12.
Centers for Disease Control and Prevention.
National Center for Health Statistics. Prevalence
Suggested Reading of overweight and obesity among children and
adolescents: United States, 1963–1965 through
Aaron DL, Patel A, Kayiaros S, Calfee 2011–2012. (n.d.). Last reviewed 6 Nov 2015;
R. Four common types of bursitis: diagno- last updated 9 Sep 2014. https://www.cdc.gov/
sis and management. J Am Acad Orthop Surg. nchs/data/hestat/obesity_child_11_12/obesity_
2011;19(6):359–67. child_11_12.htm. Accessed 22 Nov 2018.
Al-Rimawi H, Jallad S. Sport participation in Colosimo AJ, Ireland ML. Thigh compartment
adolescents with sickle cell disease. Pediatr syndrome in a football athlete: a case report and
Endocrinol Rev. 2008;6(Suppl 1):214–6. review of the literature. Med Sci Sports Exerc.
Barker AR, Gracia-Marco L, Ruiz JR, Castillo MJ, 1992;24(9):958–63.
Aparicio-Ugarriza R, González-Gross M, et al. Dick NA, Diehl JJ. Febrile illness in the athlete.
Physical activity, sedentary time, TV view- Sports Health. 2014;6(3):225–31.
Dobbe AM, Gibbons PJ. Common pediatric condi- Silva PV, Kamper SJ, da Cunha Menezes Costa
tions of the lower limb. J Paediatr Child Health. L. Exercise-based intervention for prevention
2017;53(11):1077–85. of sports injuries (PEDro synthesis). Br J Sports
Gessel LM, Fields SK, Collins CL, Dick RW, Med. 2018;52(6):408–9.
Comstock RD. Concussions among United Styn NR, Wan J. Urologic sports injuries in chil-
States high school and collegiate athletes. J Athl dren. Curr Urol Rep. 2010;11(2):114–21.
Train. 2007;42(4):495–503. Tisano BK, Estes AR. Overuse injuries of the pedi-
Gillett JG, Lichtwark GA, Boyd RN, Barber atric and adolescent throwing athlete. Med Sci
LA. Functional anaerobic and strength training Sports Exerc. 2016;48(10):1898–905.
in young adults with cerebral palsy. Med Sci Tsai CH, Hsu CJ, Hung CH, Hsu HC. Primary
Sports Exerc. 2018;50(8):1549–57. traumatic patellar dislocation. J Orthop Surg
Hendrix CL. Calcaneal apophysitis (sever disease). Res. 2012;7:21.
Clin Podiatr Med Surg. 2005;22(1):55–62, vi. Vuurberg G, Hoorntje A, Wink LM, van der
Ip P, Ho FK, Louie LH, Chung TW, Cheung YF, Doelen BFW, van den Bekerom MP, Dekker
Lee SL, et al. Childhood obesity and physical R, et al. Diagnosis, treatment and prevention of
activity-friendly school environments. J Pediatr. ankle sprains: update of an evidence-based clin-
2017;191:110–6. ical guideline. Br J Sports Med. 2018;52(15):
Neurologic disorders. MSD manual professional 956.
version. Kenilworth: Merck & Co; 2018. https:// White ND, Noeun J. Performance-enhancing
www.merckmanuals.com/professional/neuro- drug use in adolescence. Am J Lifestyle Med.
logic-disorders. Accessed 11 Nov 2018 2017;11(2):122–4.
Patel DR, Villalobos A. Evaluation and man- Wilk KE, Arrigo CA. Rehabilitation: common
agement of knee pain in young athletes: problems and solutions. Clin Sports Med.
overuse injuries of the knee. Transl Pediatr. 2018;37(2):363–74.
2017;6(3):190–8. Yard EE, Gilchrist J, Haileyesus T, Murphy M,
Petersen W, Rembitzki I, Liebau C. Patellofemoral Collins C, McIlvain N, et al. Heat illness among
pain in athletes. Open Access J Sports Med. high school athletes – United States, 2005-2009.
2017;8:143–54. J Saf Res. 2010;41(6):471–4.
Pusateri ME, Hockenberry BJ, McGrew Zinder SM, Basler RS, Foley J, Scarlata C, Vasily
CA. Zurich to Berlin—“where” are we now DB. National athletic trainers’ association
with the concussion in sport group? Curr Sports position statement: skin diseases. J Athl Train.
Med Rep. 2018;17(1):26–30. 2010;45(4):411–28.
Rheumatology
15
Amanda G. Brown, William Blaine Lapin,
Andrea A. Ramirez, and Jennifer L. Rammel
ARTHRITIS
Juvenile Idiopathic Arthritis (JIA)
Background and Definitions
• Previous classification criteria include juve-
nile rheumatoid arthritis and juvenile chronic
arthritis.
• Arthritis (Fig. 15.1):
–– Joint stiffness is the most common
symptom.
–– Stiffness worsens with inactivity and
improves with activity.
–– Joint swelling. Fig. 15.1 9-year-old female with 3-year history of recurrent
–– Pain (may be absent). arthritis and morning stiffness, presenting with joint pain,
–– Physical exam findings: joint effusion swelling, and limping. Note the effusion and swelling of the
(swelling), joint warmth, decreased range right knee
of motion, tenderness, and pain with range
of motion. • The exact etiology is unknown, but genetic
• Enthesitis: and environmental factors are involved.
–– Inflammation of the entheses (sites of ten- • Exact incidence and prevalence is unknown
don or ligament insertion onto bone) and varies with subtypes.
–– Common sites: Achilles tendons, patellar • Oligoarticular and polyarticular subtypes are
tendons (2, 6, and 10 o’clock positions), more common among females.
greater trochanter, metatarsal heads, and • JIA is a clinical diagnosis; there is no labora-
plantar fascia tory test that makes the diagnosis.
• JIA is broadly defined as arthritis of one or • Other causes of arthritis (i.e., trauma, infec-
more joints occurring for at least 6 weeks in a tion, malignancy) must be ruled out before a
child younger than 16 years of age. diagnosis of JIA is made (Table 15.1).
Classification (Table 15.2) [1]

A. G. Brown (*) · W. B. Lapin · A. A. Ramirez · J. L. Rammel
Division of Rheumatology, Department of Pediatrics, Baylor
e-mail: Amanda.Brown2@bcm.edu

526 A. G. Brown et al.
Table 15.1 Differential diagnosis for child with arthritis Table 15.2 International League of Associations for
Autoimmune Rheumatology Classification of Juvenile Idiopathic Arthritis
Juvenile idiopathic arthritis (JIA) [1]
Inflammatory bowel disease Category Definition
Systemic lupus erythematosus Systemic onset Arthritis and fever (> 2 weeks,
Sjögren syndrome JIA documented quotidian × 3 + days), plus
Vasculitis (e.g., Henoch-Schönlein purpura, Kawasaki one or more of the following:
disease) evanescent erythematous rash,
Neoplastic generalized lymphadenopathy,
Leukemia hepatosplenomegaly, serositis
Sarcoma Oligoarthritis Arthritis in < 4 joints in the first 6
Pigmented villonodular synovitis (PVNS) months of disease
Trauma Polyarticular Arthritis in > 5 joints during the first 6
Infection rheumatoid months of disease and RF-negative
Septic joint (most common pathogens: Staphylococcus factor
spp., Streptococcus spp., Kingella spp.) (RF)-negative
Tuberculosis Polyarticular Arthritis in > 5 joints during the first 6
Osteomyelitis rheumatoid months of disease and RF-positive × 2
Lyme disease factor at least 3 months apart
Neisseria gonorrhoeae (RF)-positive
Infection-associated Psoriatic arthritis
Arthritis and psoriasis or arthritis plus
Acute rheumatic fever two of the following: dactylitis, nail
Post-streptococcal reactive arthritis pitting or onycholysis; psoriasis in a
Reactive arthritis first-degree relative
Hematologic diseases Enthesitis- Arthritis and enthesitis, or arthritis, or
Sickle cell disease related arthritis enthesitis, plus two or more of the
Hemophilia (ERA) following: sacroiliac joint tenderness or
Autoinflammatory diseases inflammatory lumbosacral pain,
Familial Mediterranean fever HLA-B27 +; onset of arthritis in a male
Sarcoidosis/Blau syndrome older than age 6 years; acute anterior
Cryopyrin-associated periodic syndrome (CAPS) uveitis; history of ankylosing
spondylitis, ERA, sacroiliitis with
inflammatory bowel disease, reactive
Oligoarticular JIA arthritis, or acute anterior uveitis in a
first-degree relative
• Most common subtype of JIA. Undifferentiated Arthritis that fulfills criteria for no
• Most commonly affects females between 2 arthritis category or two or more categories
and 4 years of age.
• Joint involvement: walks with a limp in the morning or after
–– Most common joint affected is the knee. naps. She is otherwise well, and infections
Other joints (wrists, ankles) can be affected. and malignancies have been ruled out.
Joint involvement is asymmetric. • Exclusion criteria:
–– Arthritis in < 4 joints during the first –– Psoriasis in a child or first-degree relative
6 months of disease: ––
HLA-B27+ male older than age 6 years,
◦◦ Persistent oligoarticular JIA: < 4 joints ankylosing spondylitis/enthesitis-related
throughout disease course arthritis/sacroiliitis with inflammatory bowel
◦◦ Extended oligoarticular JIA: > 4 joints disease (IBD)/reactive arthritis or acute ante-
affected beyond 6 months rior uveitis in a first-degree relative
• Classic clinical vignette: ––
Rheumatoid factor (RF) positive in two
–– 2-year-old Caucasian female with persis- assessments 3 months apart
tently swollen knee whose parents note she –– Systemic-onset JIA in a child
15 Rheumatology 527
• Antinuclear antibody (ANA) is positive in E nthesitis-Related Arthritis (ERA)

approximately 50% of children with JIA and
confers an increased risk of uveitis. • Background
–– More commonly affects males.
–– Prevalence: approximately 10% of chil-
Polyarticular JIA dren with JIA.
–– Mean age of onset: 12 years of age.
• Bimodal incidence in children 1–3 years of –– Commonly involves axial skeleton (spine,
age and again in adolescence. sacroiliac joints), although spine involve-
• Children are either RF positive or negative, ment is less common than in adult-onset
based on positive testing found on two occa- disease.
sions 3 months apart. • Classic findings:
• RF-negative disease more common in –– Joint involvement pattern: Arthritis is usu-
Caucasians, while RF-positive disease more ally pauciarticular (< 5 joints involved).
common in non-whites. –– Ankylosing spondylitis; axial involvement
• RF-positive polyarthritis is a more aggressive does not typically occur early in disease
disease and closely approximates adult rheu- course.
matoid arthritis. –– Axial involvement found in roughly one-
• Fatigue and weight loss may be present with third of children.
severe disease (unlike oligoarthritis). –– May develop acute-onset, symptomatic
• Joint involvement: uveitis. Other subtypes of JIA present with
–– Children have more than 4 joints involved asymptomatic uveitis. Uveitis may occur
within the first 6 months of disease. before arthritis.
–– Large and small joints are affected. Joint –– HLA-B27 may be present or absent and is
involvement pattern is symmetric. not required for diagnosis.
–– Temporomandibular and cervical spine –– Associated with IBD (may screen with
joints may be involved and are more com- fecal calprotectin, a marker for intestinal
monly affected in RF-negative children. inflammation).
• Classic clinical vignette: • Exclusion criteria:
–– 15-year-old female with swelling of bilat- –– Psoriasis in a child or first-degree relative
eral ankles, wrists, and proximal interpha- –– RF positive in two assessments 3 months
langeal joints. She complains of morning apart
stiffness lasting 2 h per day and d ifficulty –– Systemic-onset JIA in a child
with daily activities such as writing, typ- • Axial disease requires anti-tumor necrosis
ing, and fastening buttons. factor (TNF) therapy.
• Exclusion criteria: • Complications:
–– Psoriasis in a child or first-degree relative, –– Acute-onset, symptomatic uveitis, cardio-
HLA-B27+ male older than age 6 years vascular disease (aortic regurgitation)
–– Ankylosing spondylitis/enthesitis-related
arthritis/sacroiliitis with IBD/reactive
arthritis or acute anterior uveitis in a first- Psoriatic JIA
degree relative
–– Rheumatoid factor (RF) positive in two • Bimodal peak onset: at 2–4 years of age and
assessments 3 months apart mid- to late childhood.
–– Systemic-onset JIA in a child • Mean age of onset is roughly 9 years of age.
• May present with arthritis with psoriasis. –– Rash described as salmon-colored macular
• Prevalence is approximately 6–10% of chil- or papular that appears during fever spikes
dren with JIA. and usually involves the trunk, neck, and
• Classic findings: proximal extremities. Rash is typically
–– Psoriasis, nail pitting, nail ridging, or non-pruritic, and stroking of the skin elicits
onycholysis. Koebner phenomenon.
–– Psoriasis does not have to be present if –– In addition to arthritis, arthralgias, myal-
there is a family history in at least one first- gias, and tenosynovitis may be present.
degree relative. Arthritis may not be present at diagnosis,
–– Joint involvement pattern: but most children will develop arthritis
◦◦ Arthritis is usually pauciarticular (< 5 within 3 months of disease onset.
joints involved). –– Joint involvement may be oligoarticular or
◦◦ Distal interphalangeal joints (DIP) are polyarticular and if left untreated often
commonly affected. leads to bony erosions and joint
◦◦ Dactylitis, “sausage digit.” destruction.
◦◦ Arthritis may precede the psoriasis by –– Lymphadenopathy is present in over one-
many years. quarter of patients.
• Exclusion criteria: –– Serositis may manifest as pericarditis, peri-
–– HLA-B27+ male older than age 6 years, cardial effusion, pleuritis, or pleural
ankylosing spondylitis/ERA/sacroiliitis effusions.
with IBD/reactive arthritis or acute anterior • Rare manifestations:
uveitis in a first-degree relative –– Septic meningitis and interstitial lung
–– RF positive in two assessments 3 months disease
apart • Approximately 10% of children will present
–– Systemic-onset JIA in a child with macrophage activation syndrome
(MAS). Mortality rate for MAS is approxi-
mately 8%.
Systemic-Onset JIA • Exclusion criteria:
–– Psoriasis in a child or first-degree rela-
• Disease characterized by fevers, arthritis, and tive, HLA-B27+ male older than age
one of the following: generalized lymphade- 6 years
nopathy, hepato- or splenomegaly, and/or –– Ankylosing spondylitis/ERA/sacroiliitis
serositis. with IBD/reactive arthritis or acute anterior
• Accounts for 10–20% of children with JIA. uveitis in a first-degree relative, RF posi-
• Peak age of onset is 1–5 years of age, although tive in two assessments 3 months apart
the disease may present at anytime during
childhood.
• Infections and malignancy must be ruled out M acrophage Activation Syndrome
first as cause of fevers. Bone marrow biopsy (MAS)
is recommended to rule out malignancy.
• Classic findings: Background
–– Classic fever pattern is a quotidian fever. • Most commonly a complication of systemic-
Children are often well appearing between onset JIA.
fever spikes. • May be seen with other rheumatic diseases.
15 Rheumatology 529
• Related to hemophagocytic lymphohistiocy- –– ANA negative (oligoarticular JIA, polyar-

tosis (HLH). ticular JIA):
• May be seen in up to 10% of patients with ◦◦ Uveitis screening every 6 months
systemic-onset JIA. –– Systemic-onset JIA, ERA:
• Pathogenic mechanism related to overwhelm- ◦◦ Uveitis screening every 12 months
ing inflammatory process. • The severity and disease course may not cor-
• Patients with MAS generally appear unwell respond to the arthritis course.
and can quickly deteriorate to shock and ful- • Uveitis may develop before or after JIA

minant organ failure. diagnosis.
• Most types of uveitis associated with JIA are
Laboratory insidious and often asymptomatic.
• Pancytopenia (platelet count the first cell line • Complications of uveitis include synechiae,
to decrease) band keratopathy, glaucoma, cataracts, and
• Elevated serum ferritin blindness.
• Prolongation of the prothrombin time and • Treatment: topical glucocorticoid eye

partial thromboplastin time, elevated D-dimer drops, topical mydriatic eye drops, second-
• Low or decreasing fibrinogen line agents same as for arthritis to achieve
• Elevated transaminases early in MAS as high remission and avoid long-term steroid
as 1000s drops.
• Falling erythrocyte sedimentation rate (ESR)
with rising or persistently elevated CRP
• Elevated triglycerides aboratory Abnormalities in JIA
L
• Hemophagocytosis (bone marrow, lymph
nodes, liver, or spleen) • JIA is a clinical diagnosis. It cannot be diag-
nosed by a blood test.
Treatment • Laboratory data help to exclude other causes
• Prompt treatment is critical. of arthritis.
• Prognosis: fatality in 5–10% of cases. • Synovial fluid analysis can be helpful to rule
• Corticosteroids and cyclosporine can prevent out septic arthritis.
life-threatening complications. • Nighttime pain, pain out of proportion to
exam, or abnormalities in complete blood
count (CBC) should prompt workup for leu-
Uveitis kemia or lymphoma. Consider screening
with uric acid and lactate dehydrogenase
• Screening based on ANA status, age at diag- level.
nosis, and JIA subtype. • CBC may be normal. May show normocytic
• Screening recommendations for children anemia (if chronic inflammation has been
with JIA without known uveitis: [2] present) or mildly elevated platelet value
–– ANA positive (oligoarticular JIA, polyar- (indicative of inflammatory state).
ticular JIA) depending on the age of onset: • Inflammatory markers C-reactive protein
◦◦ Onset age < 7 years of age (CRP), erythrocyte sedimentation rate (ESR)
▪▪ Uveitis screening every 3–4 months may be normal or elevated.
◦◦ Onset age > 7 years of age • Expect to see elevated CRP, ESR, and ferritin
▪▪ Uveitis screening every 6 months in untreated systemic-onset JIA.
• ANA is present in ~50% of children with JIA cam, celecoxib, and indomethacin. All come
but is not helpful for making diagnosis. ANA in liquid form except celecoxib, which can be
status is helpful for outlining risk of uveitis sprinkled.
(see below). Positive ANA may be detected in • NSAIDs usually insufficient to control most
10–30% of healthy pediatric population or forms of arthritis.
after infection. Immunofluorescence method • Adverse effects:
is the gold standard test method. –– Abdominal pain.
• Only 10% of children with JIA are RF –– Hematologic, renal, hepatic, and neuro-
positive. logic adverse effects may occur.
–– Naproxen can cause pseudoporphyria, a
bullous rash in fair-skinned children that
Imaging occurs after sun exposure.
• Conventional radiographic imaging may be Steroids

normal, especially in acute setting. • Intra-articular corticosteroid injections.
• Ultrasound may be useful to detect joint –– May be very effective in cases of
effusions. oligoarthritis
• Magnetic resonance imaging (MRI) with- • Systemic therapy: required if above therapies
out contrast can detect synovitis and joint fail to achieve inactive oligoarticular disease,
damage (joint space narrowing, bony if frequent (> 3 per year) joint injections are
erosions). required, or if disease extends to involve addi-
• Synovial enhancement (indicating active dis- tional joints.
ease) may be better seen with addition of con- • Oral or intravenous (IV) corticosteroids may
trast to MRI protocol. be used initially in severe polyarthritis or sys-
temic disease, but prolonged use is avoided
due to their adverse effects.
Complications of JIA • The following adverse effects are high
yield:
• Osteopenia/osteoporosis may occur. –– Immunosuppression
• Untreated arthritis can lead to muscle atro- –– Adrenal suppression
phy, limb length discrepancy, or permanent –– Increased appetite/weight gain/Cushingoid
joint damage. features
• Untreated arthritis can lead to permanent –– Acne
skeletal deformity. –– Mood changes
• Psychosocial factors such as anxiety and –– Osteoporosis/avascular necrosis
school absenteeism. –– Cataracts
• Macrophage activation syndrome. –– Hypertension
• Uveitis. –– Increased intraocular pressures
–– Steroid-induced diabetes
Treatment of JIA Disease-Modifying Antirheumatic Drugs
(DMARDs)
Nonsteroidal Anti-inflammatory Drugs
• Methotrexate:
(NSAIDs)
–– Mechanism of action: Folate analogue
• The most commonly used NSAIDs in chil-
competitively inhibits dihydrofolate reduc-
dren include ibuprofen, naproxen, meloxi-
15 Rheumatology 531
tase leading to inhibition of DNA synthesis –– Elevated liver enzymes

and purine metabolism. –– Local injection site reactions, infusion
–– May be administered orally or reactions/anaphylaxis
subcutaneously. –– Cytopenias (neutropenia),
–– May take 6–12 weeks to achieve full hypogammaglobulinemia
effectiveness. –– Increased risk of malignancy (“black box”
–– Folic acid is routinely given to decrease warning)
adverse (gastrointestinal) effects (nausea, –– Live virus vaccines contraindicated
vomiting, oral ulcers).
–– Other adverse effects: elevated liver Prognosis
enzymes (usually transient), leukopenia/ • Prognosis varies based on subtype.
immunosuppression, and teratogenicity. • Approximately 50% of children who have
◦◦ Blood counts and liver enzymes are JIA continue to have active disease into
monitored after 4 weeks of therapy and adulthood.
then every 3 months while a child is tak- • Poor prognostic factors include arthritis of
ing methotrexate. the hip, cervical spine, ankles, or wrists,
–– Long-term methotrexate appears to be safe prolonged systemic inflammation, radio-
and highly effective. logic evidence of joint deformity, and RF or
anti-cyclic citrullinated peptide (CCP)
Biologics antibodies.
• Anti-TNF-alpha agents:
–– Etanercept: weekly or twice-weekly sub-
cutaneous injection Other Arthritides of Childhood
–– Adalimumab: biweekly subcutaneous
injection Post-streptococcal Reactive Arthritis
–– Infliximab: monthly IV infusion • Distinct from arthritis of acute rheumatic
• Anti-IL-6 agent: fever (ARF). Patients do not meet criteria for
–– Tocilizumab: IV infusion or subcutaneous ARF (see Chap. 19 Cardiology).
injection • Post-streptococcal reactive arthritis (PSRA)
–– Can be used for polyarticular JIA or sys- joint involvement pattern is additive and per-
temic-onset JIA sistent and can involve small joints, entheses,
• Anti-IL-1 agents: or axial skeleton.
–– Anakinra, canakinumab • PSRA usually involves joints of lower
–– Daily or monthly subcutaneous injectable extremities.
agents • Incidence is bimodal with peak between 8
–– Used for systemic-onset JIA and 14 years of age and again in early
• Abatacept (T-cell co-stimulator inhibitor) and adulthood.
rituximab (anti-CD20) are less commonly • PSRA has less dramatic response to NSAID
used agents. therapy as compared to arthritis of ARF.
• Common adverse effects of biologics: • If arthritis is unresponsive to NSAIDs, a brief
–– Immunosuppression/increased risk of oral steroid course is very effective.
infections • Secondary antibiotic prophylaxis against
–– Opportunistic infections group A β-hemolytic streptococcus (GAS)
–– Tuberculosis reactivation (must screen for recommended for 1 year if there’s no evi-
before initiation) dence of carditis
Arthritis Associated intra-articular corticosteroid injections in

with Inflammatory Bowel Disease select cases
(IBD)
• Incidence is equal in boys and girls.
Juvenile Systemic Lupus
• Arthritis may be associated with IBD flares; Erythematosus (jSLE)
peripheral joints are commonly affected.
Background
• Extra-articular skin disease may include oral
• jSLE is a chronic, multisystem, autoimmune
ulcers, erythema nodosum, and pyoderma
disease with antibody to nuclear antigen.
gangrenosum.
Immune complex formation causes damage
to affected tissues. Any organ can be affected.
Reactive Arthritis jSLE has an unpredictable presentation and
disease course. Pediatric patients have more
• Formally known as Reiter syndrome. severe disease.
• Reactive arthritis is a type of arthritis associ- • Average age of onset is 12 years. Mean age of
ated with an infection at a distant site, distinct diagnosis is 13 years.
from that of the affected joints. • Before puberty, the male/female ratio is 3:4,
• Common infectious triggers: Yersinia spp., but after puberty it increases to 1:9.
Salmonella spp., Shigella spp., Campylobacter • Incidence 2.22 per 100,000 people in the
spp., and Chlamydia spp. United States. Prevalence 9.73 per 100,000
• 3:1 male predominance. people.
• Common mucocutaneous findings: oral • Incidence of jSLE is higher in Hispanic,
ulcers, urethritis, cervicitis, circinate balani- Native American, Pacific Islander, and Asian
tis, and keratoderma blennorrhagicum. individuals than in white individuals.
• Male children and those who are HLA-B27 • Pediatric patients may not meet the adult
positive tend to have more severe disease. classification criteria in Table 15.3 [3, 4].
• Bilateral mucopurulent conjunctivitis and
symptomatic uveitis may occur. Clinical Presentation (see Table 15.3)
• Other associated symptoms: arthralgia, fever,
General Manifestations
weight loss, and malaise.
• Fatigue
• Symptoms begin a few days to 6 weeks after
• Fever
infection and may last weeks to months.
• Weight loss
Diagnosis • Lymphadenopathy
• Synovial fluid tests can be helpful in exclud- • Hepatosplenomegaly
ing other disease processes. HLA-B27 posi-
Cutaneous Manifestations
tivity is supportive of the diagnosis. Imaging
• Hallmark: malar or “butterfly” rash:
studies can be normal but should be obtained,
–– Develops on the malar eminences and
particularly if other disorders such as pyo-
crosses the nasal bridge while sparing the
genic arthritis or osteomyelitis are
nasolabial folds.
considered.
–– The forehead and chin also may be
Treatment affected.
• NSAIDs (first-line), pathogen-specific antibi- –– Rash can appear as a blush or a maculo-
otics, sexually transmitted infections (STI) papular eruption with an associated scale
treatment for individual and sexual partners, and usually is non-pruritic.
15 Rheumatology 533
Table 15.3 Classification criteria for juvenile systemic –– Very common in SLE

lupus erythematosus [3, 4] –– Symmetric involvement of both the large
Malar rash and small joints
Discoid rash –– Primarily the knees, wrists, ankles, and
Photosensitivity
Oral or nasal ulcers
fingers
Arthritis –– Jaccoud arthropathy (ulnar deviation of the
Nonerosive arthritis involving ≥ 2 peripheral joints second to fifth fingers and subluxation of
Serositis the metacarpophalangeal joints)
Pleuritis: Convincing history of pleuritic pain or rub • Morning stiffness
heard by physician or evidence of pleural effusion, or
Pericarditis: Documented by EKG, or rub, or evidence
• Tenosynovitis
of pericardial effusion • Myalgia and myositis
Renal manifestation
Persistent proteinuria > 0.5 g/day, or > 3 + if Renal Manifestations
quantification not performed, or cellular casts: May be
• Lupus nephritis (LN) is a glomerulonephritis
red cells, hemoglobin, granular, tubular, or mixed that is the greatest contributor to morbidity
Neurological manifestations
Seizure or psychosis in absence of any other causes and mortality in the jSLE population. 18% to
Hematologic manifestations 50% develop end-stage renal disease.
Hemolytic anemia with reticulocytosis, or • LN may manifest as proteinuria, microscopic
Leukopenia: < 4,000/mm3 total on two or more hematuria, hypertension, or elevated blood
occasions, or
urea nitrogen and creatinine levels.
Lymphopenia: < 1,500/mm3 on two or more occasions,
or • Among patients, 20–75% may develop
Thrombocytopenia: < 100,000/mm3 in absence of nephrotic syndrome.
offending drugs • A renal biopsy with histologic, immunofluo-
Antinuclear antibodies rescent, and electron micrographic analysis is
An abnormal titer of ANA by immunofluorescence or
necessary to classify the histologic type of
an equivalent assay at any point in time in the absence
of the drugs known to be associated with ‘drug-induced renal disease.
lupus’ syndrome • 80% of LN develops in the first year of
EKG electrocardiogram, ANA antinuclear antibody diagnosis.
• Treatment is induction with cyclophospha-
• Discoid lupus: mide or mycophenolate mofetil (MMF) and
–– Coin-shaped erythematous rash. then maintenance with MMF or
–– May affect the face, ears, and scalp, azathioprine.
although the upper extremities and trunk
can be affected. Neuropsychiatric Manifestations
–– The central area may be hypopigmented. • Headaches: most common
–– Active border may appear hyperpigmented. • Decreased concentration
–– The lesions may heal with a scar or atrophy. • Cognitive dysfunction
–– Discoid patches on the scalp may result in • Mood disorders
scarring alopecia if the hair follicle is • Psychosis
damaged. • Seizures
• Mucosal ulcerations • Peripheral nervous system involvement
• Periungual erythema • Central nervous system (CNS) vasculitis
• Alopecia • Stroke
• Movement disorders such as chorea
Musculoskeletal Manifestations • Pseudotumor cerebri
• Arthralgia and nonerosive arthritis:
Hematologic Involvement • Bacterial endocarditis

• Leukopenia • Lupus valvulitis (Libman-Sacks endocardi-
• Lymphopenia tis): may predispose patients undergoing den-
• Anemia (usually hemolytic) tal procedures to bacterial endocarditis
• Thrombocytopenia • Premature atherosclerosis
• Coagulation abnormalities
Gastrointestinal Manifestations
Antiphospholipid Antibody Syndrome (APS) • Abdominal pain, diarrhea, vomiting (most
• Positive lupus anticoagulant, anticardiolipin common)
antibody, or anti-β2 glycoprotein 1 antibody • Acute lupus peritonitis
in the setting of vascular thrombosis or preg- • Acute pancreatitis caused by active jSLE,
nancy morbidity infection, or corticosteroid use
• Can present as follows: • Enteritis or mesenteric vasculitis, patients at
–– Stroke risk of bowel perforation
–– Transient ischemic attack • Protein-losing enteropathy
–– Chorea • Intestinal pseudo-obstruction
–– Recurrent fetal loss • Liver transaminitis
–– Avascular necrosis • Lupus hepatitis
–– Myocardial infarction
–– Organ infarction Endocrine Manifestations
–– Livedo reticularis • Hypothyroidism is most common.
–– Pulmonary embolism • Hyperthyroidism is rare.
–– Deep vein thrombosis • Diabetes mellitus type II may develop as a
• Laboratory abnormalities: result of corticosteroid use and obesity.
–– Elevated anticardiolipin, anti-β2 glycopro- • Adrenal gland failure may result due to pro-
tein 1 antibodies, and/or positive lupus longed corticosteroid use.
anticoagulant • Delayed puberty is common.
–– Prolonged partial thromboplastin time • Irregular menses or amenorrhea is common
during periods of active disease.
Pulmonary Manifestations
• Restrictive lung disease Laboratory Evaluation
• Pleuritis • CBC is needed to evaluate potential cytopenias.
• Pleural effusion • A comprehensive metabolic panel may reveal
• Pneumonitis transaminitis, hypoalbuminemia, or an ele-
• Infection vated creatinine level.
• Pulmonary hypertension • Elevated ESR is very common.
• Pulmonary hemorrhage: presents with short- • CRP levels can remain normal.
ness of breath and a sudden drop in hemoglo- • A urinalysis may show proteinuria, hematu-
bin concentration ria, and other components of active urinary
sediment.
Cardiac Manifestations • The ANA is positive in 99% of patients with
• Pericarditis SLE, but also may be positive in other rheu-
• Pericardial effusion matic diseases such as mixed connective tis-
• Myocarditis sue disease and dermatomyositis.
15 Rheumatology 535
• The ANA also may be positive in up to one- –– Improves rash

third of the healthy population and in family –– Nephritis or severe organ involvement
members of patients with SLE. • MMF for disease control and lupus nephritis
• A negative ANA makes the diagnosis of SLE
extremely unlikely, and ANA is not useful to
monitor disease activity. eonatal Lupus Erythematosus
N
• The anti-double-strand DNA (dsDNA) is (NLE)
very specific for SLE and may be found in
> 75% of patients. Background
• The anti-dsDNA level is usually checked at • NLE occurs in 1% of infants who experience
the time of diagnosis and throughout the transplacental passage of maternal SS-A or
disease course to monitor disease activity. SS-B antibodies.
• The anti-Smith antibody is highly specific for
SLE and may be found in up to 50% of patients. Clinical Presentation
• The anti-ribonucleoprotein (RNP) antibody • Congenital heart block (CHB) from antibody-
may be found in patients who have classic mediated damage to the conducting system is
SLE but often indicates that the patient’s the most serious complication and may be
diagnosis is a mixed connective tissue disease seen in up to 30% of infants born with NLE.
(SLE with features of systemic sclerosis or • Fetal bradycardia is the first sign of NLE and
dermatomyositis). must be evaluated at 16 weeks gestation and at
• SS-A (anti-Ro) and SS-B (anti-La) antibodies continuing intervals throughout pregnancy.
are common. • Cytopenias and hepatitis can occur.
• Complement levels (C3 and C4) are low in • Cutaneous neonatal lupus (without heart
SLE during periods of active disease. involvement) is the most common form of
NLE:
Management –– The rash is erythematous with a raised bor-
• Hydroxychloroquine: der, particularly prominent on sun-exposed
–– One of the mainstays of treatment for any areas and around the eyes; the skin may
patient with SLE have a fine scale.
–– Prevents disease flares
–– Adverse effects: Treatment
◦◦ Some patients may suffer abdominal • In CHB, treatment is controversial and con-
discomfort. sists of dexamethasone or intravenous immu-
◦◦ Potential retinal toxicity of treatment for noglobulin (IVIG).
any patient with SLE • Cutaneous NLE does not require treatment.
–– Improves rash:
◦◦ Requires baseline ophthalmology visit Prognosis
with follow-up every 6–12 months • 30% to 50% of infants who develop CHB will
• Methotrexate for arthritis require pacemaker implantation within the
• Prednisone for disease control and disease first 24 months.
flares • Noncardiac manifestations will resolve with-
–– Cyclophosphamide for lupus treatment for out intervention, usually within 6 months when
any patient with SLE maternal antibodies are no longer present.
Drug-Induced Lupus (DIL) Clinical Presentation

• Calcinosis, Raynaud phenomenon (swollen
Background hands or fingers), esophageal dysmotility,
• The prevalence of DIL is equal in males and sclerodactyly, and telangiectasia (CREST)
females, although minocycline-induced lupus syndrome and positive centromere antibodies
is usually seen in adolescent girls using the • Diffuse systemic scleroderma is more fre-
medication for treatment of acne. quent with lung and renal involvement, posi-
• Chronic use of the medication is required to tive SCL-70 (topoisomerase)
develop DIL.
• Medications that more commonly induce Management
DIL include minocycline, procainamide, • Angiotensin-converting enzyme (ACE)
hydralazine, penicillamine, isoniazid, quini- inhibitor.
dine, phenytoin, carbamazepine, infliximab, • Calcium (Ca) channel blocker, e.g., nifedipine.
adalimumab, and etanercept. • Alpha blocker, e.g., doxazosin.
• Dipyridamole (e.g., Persantine, Boehringer
Clinical Presentation Ingelheim, Ridgefield, CT).
• Patients often present with constitutional • Corticosteroid can exacerbate renal crisis!
symptoms, photosensitive rash, arthralgia,
myalgia, and serositis.
• Subacute cutaneous lupus also may be Localized Scleroderma
present.
Background
Diagnosis • Most common form in children, also called
• Positive antihistone antibodies are present in linear scleroderma, morphea, deep morphea,
95% of patients with DIL. or generalized morphea
Treatment of DIL Clinical Presentation

• Discontinue the offending agent. • Lesions can involve the face (en coup de
• A trial of NSAIDs, hydroxychloroquine, and sabre, dueling stroke from a sword); lesions
possibly corticosteroids may be needed. can become more indurated, extending deeper
• Symptoms usually abate within weeks to into muscle and bone (melorheostosis). Facial
months of stopping the medication; however, lesions can be associated with seizure, uve-
in some patients, DIL will evolve into true itis, dental defects, and facial abnormalities.
SLE.
Diagnosis
• All lab tests are usually normal, including
Systemic Scleroderma SCL-70, centromere antibodies, RNP, Smith,
and SS-A.
Background • Anti-single-strand DNA antibodies may be
• Scleroderma is characterized by skin indura- found positive.
tion and thickening accompanied by various
degrees of tissue fibrosis and chronic inflam- Treatment
matory infiltration in numerous visceral • Methotrexate and steroids can improve and
organs, prominent fibroproliferative vascu- resolve active lesions. Older sclerosed lesions the
lopathy, and humoral and cellular immune care is mainly supportive. Complications such as
alterations. seizure or uveitis are treated appropriately
• Physical therapy if joints are involved
15 Rheumatology 537
Prognosis Clinical Presentation

• With treatment lesions can resolve or become • Recurrent parotitis (68%)
stable, and joint function can be preserved. • Keratoconjunctivitis sicca (8%, can cause
Lesions can spontaneously become inactive recurrent dental caries)
within 3–4 years without treatment, however • Lymphadenopathy
there can be disability and damage. • Fatigue
• Arthralgia
• Renal disease
Mixed Connective Tissue Disease • Neurologic symptoms
(MCTD) • Rash
• Adult classification criteria include Raynaud • Antibodies: anti-Ro (SS-A) and/or anti-La
phenomenon and high-titer RNP antibody (SS-B)
and at least one sign from at least two of the
following diseases: SLE, systemic sclerosis, Associated Diseases
or polymyositis. • SLE
• More common in girls. • Rheumatoid arthritis
• Scleroderma
Clinical Presentation • Biliary cirrhosis
• Raynaud phenomenon
• Arthritis and joint abnormalities Management
• Fever and fatigue • Artificial tears
• Dorsal hand edema • Pilocarpine tablets
• Rash • Hydroxychloroquine for skin rash
• Myositis • Methotrexate or NSAIDs for arthritis
• Acute pericarditis
• Pericardial effusion Prognosis
• Mitral valve prolapse • These children do very well but are at risk of
• Dysphagia developing lymphomas in adulthood.
• Restrictive lung disease
• Renal disease
INFLAMMATORY MYOPATHIES
Diagnosis
• Positive anti-RNP antibodies, ANA, RF, and J uvenile Dermatomyositis (JDM)
hypergammaglobulinemia
Background
Treatment • A systemic autoimmune disorder involving
• Similar to SLE cutaneous findings, myositis, and vasculopa-
thy affecting children younger than 18
• Peaks between 5 and 14 years
Sjögren Syndrome • 2:1 female predominance
• Rare disease—approximately 1 in a million
Background
• A slowly progressive inflammatory disorder Clinical Presentation
that involves the exocrine glands: rare in • Systemic features:
pediatric patients –– Fever
–– Malaise Treatment
–– Fatigue • Depends on the organ involved and severity
–– Anorexia of disease.
–– Weight loss • Most begin with steroids, hydroxychloro-
• Musculoskeletal manifestations: quine, IVIG, and methotrexate.
–– Muscle weakness is symmetric and proxi-
mal and can be associated with muscle Prognosis
pain or stiffness. • Most patients fall into one of three categories:
–– Arthritis. –– Monocyclic disease 25%
• Cutaneous findings: –– Polycyclic disease 25%
–– Gottron papules –– Chronic continuous 50%
–– Heliotrope rash • 65% to 80% will end up with a normal to
–– Periungual erythema good functional outcome.
–– Malar rash
–– “Shawl sign” rash
–– Photosensitivity Polymyositis
–– Skin ulceration
Background
–– Calcinosis
• Uncommon in pediatrics
–– Lipodystrophy
• 2:1 female to male
–– Generalized, pruritic, scaly rash
• Median age of onset: 12.1 years
• Vasculopathy:
–– Gastrointestinal disease Clinical Presentation
–– Gingivitis • Does not have any cutaneous features
–– Raynaud phenomenon • Often has a more severe illness onset
• Pulmonary/airway: • Tends to have higher creatine kinase (CK)
–– Interstitial lung disease levels than in JDM patients
–– Dysphonia due to muscle weakness • Can have both proximal and distal weakness
and more associated falls
Diagnosis
• Diagnosis is based on the 1975 Bohan and Diagnosis
Peter classification criteria [5]: • Diagnosis is also based on the 1975 Bohan
–– Symmetric proximal muscle weakness and Peter classification criteria [5] as listed
–– Elevation of skeletal muscle enzymes before, with no requirement for skin findings.
–– Abnormal electromyography (EMG) results • Need to confirm with muscle biopsy.
–– Abnormal muscle biopsy
–– Typical skin rash of JDM (must have for Treatment
diagnosis) • Depends on the organ involved and severity
• 3/5, probable JDM diagnosis; 4/5, definite of disease.
JDM diagnosis • Most begin with steroids, hydroxychloro-
• Many modern experts accept abnormal MRI quine, IVIG, and methotrexate.
findings in place of muscle biopsy.
• Consider age-appropriate malignancy screen- Prognosis
ing in atypical cases, as this rarely can be • 50% have a chronic disease course.
linked with JDM (up to 40% in adults). • 30% end up using a wheelchair.
15 Rheumatology 539
AUTOINFLAMMATORY –– Expect to see significantly elevated CRP

and possible leukocytosis during flare.
DISEASES
Treatment
General Background
• Depends on whether the symptoms are inter-
• Autoinflammatory diseases refer to disorders
fering with routine or affecting growth.
of the innate immune system.
• Prednisone can be given but should be used
• These include various syndromes associated
with caution, as it can increase the frequency
with recurrent fever, rash, poor growth, and
of fever cycles.
elevated inflammatory markers.
• Children with persistent cases can be started
on colchicine therapy.
eriodic Fever Syndromes: Periodic
P • In refractory cases, there has been some evi-
dence that tonsillectomy is curative in 80%.
Fever, Aphthous Stomatitis,
Pharyngitis, Cervical Adenitis Prognosis
Syndrome (PFAPA) • Most children grow out of the illness by late
childhood into adolescence.
Background
• Most common periodic fever syndrome of
childhood Familial Mediterranean Fever (FMF)
• Mean age of onset, 3 years; range, 6 months
to 7 years Background
• Most common monogenic autoinflammatory
Clinical Presentation syndrome
• Fever episodes generally last 2–3 days. • Results from autosomal recessive mutations
• Episodes occur approximately every 4 weeks. in the MEFV gene
• Presents with fever and any combination of • Most common in families from the Middle
the following: East and Mediterranean areas
–– Aphthous ulcers
–– Cervical adenitis Clinical Presentation
–– Pharyngitis • 90% of cases begin before the age of 20 years.
–– Abdominal pain • Fever episodes last 1–3 days and recur every
–– Poor appetite few weeks to months.
–– Fussiness • Inflammation affects a variety of organ sys-
–– Arthralgias tems and can manifest as the following:
–– Arthritis –– Pleuritis
–– Headache –– Peritonitis
• Children are in a good health between episodes. –– Arthritis
–– Myalgia
Diagnosis –– Rash
• Clinical diagnosis –– Irritability
• No known gene association –– Poor appetite
• Obtaining CBC, ESR, and CRP at baseline –– Poor growth
and during a flare recommended:
Diagnosis • Imaging of choice: MRI, which can show

• Genetic testing is available and is diagnostic. early osteitis, bone marrow edema, and the
• ESR, CRP, fibrinogen, and white blood cell classic mixed osteolytic and sclerotic lesions
(WBC) counts may be elevated during the with or without periosteal reaction that are
episodes of fever and then normalize in classic for CRMO.
between flares. • Bone biopsy should be sterile on culture and may
show a predominance of inflammatory cells.
Treatment
• Children with persistent cases should be Treatment
started on colchicine therapy. • NSAIDs are first-line therapy.
• Treatment is generally life-long, as there is a risk • Refractory disease or areas that are more
of amyloidosis from untreated inflammation. axial or prone to instability may require anti-
TNF therapy.
Prognosis
• Good overall, if renal amyloidosis can be Prognosis
avoided, as FMF patients with end-stage renal • Most patients have periods of flares and
disease have a lower survival rate with remissions.
hemodialysis • CRMO resolves in most after several years,
generally with no long-term sequelae.
hronic Recurrent Multifocal

C
Osteomyelitis (CRMO) Sarcoidosis
• A rare autoinflammatory bone disorder • A multisystem autoinflammatory granuloma-
• Two to four times more likely in females tous disease.
• Peak onset between 7 and 12 years old • There are two primary forms of pediatric
sarcoidosis:
Clinical Presentation –– Childhood-onset sarcoidosis, also known
• Localized bone pain with or without fever. as Blau syndrome
• Can also have adjacent soft tissue swelling –– Pediatric-onset adult sarcoidosis
above lesions. • This is a rare diagnosis in childhood.
• Despite the name, it can be multifocal or uni- • Blau syndrome is associated with a mutation
focal and is not always recurrent. in NOD2/CARD15.
• Can affect any bone in the body, but most
commonly the following: Clinical Presentation
–– Metaphyseal region of long bones • Blau syndrome:
–– Clavicles –– Presents in early childhood with a triad of
–– Vertebral bodies granulomatous polyarthritis, uveitis, and
–– Pelvis dermatitis.
• 25% of patients will have extra-skeletal fea- – – Mean age of onset is 26 months.
tures such as a palmar-plantar rash. • Pediatric-onset adult sarcoidosis:
–– Presents in the adolescent years with vari-
Diagnosis ous systemic features:
• Radiographic imaging may show early osteo- ◦◦ Fever
penia or more chronic erosive changes. ◦◦ Pulmonary involvement
15 Rheumatology 541
◦◦ Lymphadenopathy (hilar and Prognosis

peripheral) • Ocular disease is the most devastating fea-
◦◦ Malaise ture, and up to 30% will lose their vision
◦◦ Weight loss despite therapy.
◦◦ Arthritis
◦◦ Hepatosplenomegaly
◦◦ Erythema nodosum and other rashes PAIN SYNDROMES
◦◦ Uveitis OF CHILDHOOD
◦◦ CNS involvement
▪▪ Seizures Growing Pains
▪▪ Encephalopathy
▪▪ Cranial nerve palsy Background
◦◦ Renal involvement • Growing pains are intermittent nonarticular
▪▪ Hypercalciuria pains occurring in childhood and are diag-
▪▪ Renal granulomas nosed by exclusion based on a typical history
▪▪ Proteinuria and normal physical examination findings.
• Growing pains may occur in any growing
Diagnosis child but usually present between the ages of
• Tissue biopsy is needed to confirm the 3 and 10 years.
diagnosis.
–– Hallmark is noncaseating epithelioid Clinical Presentation
granulomas. • The pain typically occurs at night and fre-
• Genetic testing is indicated in younger chil- quently is limited to the calf, thigh, or shin.
dren with concern for possible NOD2/ • Unlike inflammatory joint pain, the discom-
CARD15 mutations. fort is short-lived and relieved with heat, mas-
• There is no lab test that diagnoses sage, or mild analgesics.
sarcoidosis: • The child is otherwise healthy and asymp-
–– CBC can show pancytopenia. tomatic during the day, having no functional
–– Liver enzymes can be elevated. limitations.
–– Elevated ACE is produced by the granulo- • There may be a history of growing pains in
mas but is not diagnostic due to false posi- the family.
tives (elevated in > 75% of cases). • Importantly, the physical examination is
–– Lysozyme level can be elevated due to never associated with physical findings such
metabolically active granulomas, not spe- as swelling, redness, warmth, or fever.
cific to sarcoidosis.
–– Hypercalcemia and hypercalciuria are due Diagnosis
to overproduction or precursors by the • Clinical diagnosis: There are no specific labo-
granulomas. ratory or imaging findings associated with
growing pains.
Treatment • Further workup is indicated if the case is
• Treatment varies on the severity of illness and atypical or has other concerning features.
organs involved.
• Usually involves steroids, anti-TNF agents, Management
methotrexate, or cyclophosphamide. • Reassurance
• Supportive measures, typically does not • Use of supportive footwear, insoles, and neo-
require any further investigations prene sleeves
• Heat, massage, or mild analgesics, e.g., acet-
aminophen or ibuprofen Prognosis
• Good prognosis overall; hypermobility gen-
Prognosis erally decreases with age.
• The condition is generally regarded as benign. • Some patients have a higher risk of condition
• Most of these cases will self-resolve. evolving into a chronic pain syndrome.
enign Joint Hypermobility

B mplified Musculoskeletal Pain
A
Syndrome (BJHS) Syndrome (AMPS)
• Refers to patients who exhibit significant joint • AMPS is a term that encompasses the various
hypermobility and often develop associated pain syndromes of childhood and also
musculoskeletal pain but can be asymptomatic includes fibromyalgia and complex regional
• More common in females and often runs in pain syndrome (CRPS).
families • The pain is thought to be due to inappropriate
amplification of peripheral pain signals and is
Clinical Presentation felt as intense pain.
• Joint, foot, or muscle pain • More commonly seen in females, “high
• Transient joint effusions (should not last more achievers,” and youngest siblings.
than 3 days)
• Hyperextension of joints, flat feet with col- Clinical Presentation
lapsible arches • The pain can affect only one site of the body
• No signs of Marfan or Ehlers-Danlos or can be widespread, sometimes with associ-
syndrome ated allodynia.
• It is often preceded by a prior physical or psy-
Red Flags for Possible Inherited Condition chological trauma.
• High arched palate • The pain can be disabling for the patient;
• Ocular or cardiac lesions many times, they may be using crutches or a
• Skin hyperelasticity wheelchair or avoiding school.
• Arachnodactyly
• Velvety skin texture Diagnosis
• Based on history and physical exam.
Diagnosis • Fibromyalgia does have some additional
• Clinical diagnosis: Many will use the diagnostic criteria, including having pain in
Beighton scale. 11 out of 18 standardized tender points.
• May consider referral to genetics for further • Generally, normal labs and imaging.
testing if there’s any of the above red flags.
Treatment
Management • Multimodal: involves coordinating care with
• NSAID therapy psychology, psychiatry, and intense physical
• Physical therapy therapy.
15 Rheumatology 543
• Also need to discuss distraction techniques, • More common in adolescent girls.

desensitization, stress management, and cop-
ing strategies for chronic pain. Clinical Presentation
• Need to insist that the child participates in • Constitutional symptoms include fevers,
school and therapies and maintains a routine. night sweats, fatigue, lethargy, loss of appe-
• Need to set expectation that the pain cannot tite, and weight loss.
be made to completely disappear but can be • Affects the upper respiratory tract, lungs, and
made manageable. kidneys.
• Narcotics are not indicated in this condition. • Ophthalmic manifestations: conjunctivitis,
• NSAIDs can be tried but often do not work, episcleritis, uveitis, optic nerve vasculitis,
as this is a more neuropathic pain. and orbital pseudotumor with proptosis.
• Otic involvement: recurrent ear infections
Prognosis and hearing loss.
• With adherence to the treatments above, the • Myalgias, arthralgias, and arthritis, typically
majority of these patients will become symp- affecting large joints.
tom-free, but there is a 15% relapse rate. • Skin: palpable purpura, skin ulcers, and
mucocutaneous involvement with strawberry
gingivitis and oral ulcers
VASCULITIS • CNS and peripheral nervous system involve-
ment with headache, pachymeningitis, and
Antineutrophil Cytoplasmic peripheral nerve involvement.
Antibody (ANCA)-Associated • European League Against Rheumatism/
Vasculitis (AAV) Paediatric Rheumatology International Trials
Organisation/Paediatric Rheumatology
• Are rare primary systemic vasculitides caus- European Society (EULAR/PRINTO/PRES)
ing a necrotizing arteritis involving medium- childhood GPA criteria [6] require three of
and small-sized arteries the six:
• Include granulomatosis with polyangiitis –– Granulomatous inflammation on biopsy
(GPA), microscopic polyangiitis (MPA), and within the wall of the artery or perivascular
eosinophilic granulomatosis with polyangi- or extravascular area.
itis (EGPA) and renal limited ANCA –– Upper airway involvement with chronic
vasculitis purulent discharge or bloody nasal dis-
• Rare in children charge, epistaxis, or granulomata, saddle
• Target organs commonly affected: the lungs bridge nose or perforated nasal septum,
and kidneys also chronic or recurrent sinus
involvement.
–– Laryngo-tracheo-bronchial stenosis.
Granulomatosis with Polyangiitis –– Pulmonary involvement with imaging
(GPA) demonstrating nodules, cavitary lesions, or
infiltrates. Pulmonary hemorrhage may
Background present as hemoptysis.
• GPA (formerly known as Wegener granulo- –– ANCA positivity.
matosis) is rare but is the most common AAV –– Renal involvement with proteinuria
occurring in children. > 0.3 g/24 h or > 30 mmol/mg of urine
albumin/creatinine ratio on a spot morn- Diagnosis

ing sample, hematuria (five red blood • Nonspecific elevated ESR and CRP levels.
cells/high power field) or red blood cell • Elevated WBC and platelet counts and a nor-
casts in the urinary sediment or ≥ 2+ on mochromic, normocytic anemia.
dipstick, presence of necrotizing pauci- • Perinuclear antineutrophil cytoplasmic anti-
immune glomerulonephritis on kidney body (p-ANCA) is most specific for MPA.
biopsy.
Treatment
Diagnosis • Corticosteroids plus cyclophosphamide is
• Acute-phase reactants (ESR, CRP) are often commonly used.
elevated. • For severe organ involvement, plasmaphere-
• Abnormal renal function and urinalysis. sis is an essential therapy.
• Cytoplasmic antineutrophil cytoplasmic anti- • Maintenance therapies described include
body (c-ANCA) is most specific for GPA. mycophenolate mofetil, azathioprine, and
• Chest imaging with radiography or chest CT methotrexate.
(more sensitive).
• Biopsy of the lung or kidney showing necro-
tizing granulomatous inflammation and
Takayasu Arteritis (TA)
pauci-immune vasculitis in small- and Background
medium-sized blood vessels. • Rare, relapsing, chronic granulomatous,
large-vessel arteritis that involves the aorta
Treatment
and its major branches.
• Cyclophosphamide with high-dose glucocor-
• Called “pulseless disease” due to the absence of
ticoids (induction of remission).
peripheral pulses in the late phase of disease.
• Maintenance medication often needed.
• Females > males with the majority of chil-
dren being diagnosed in adolescence.
Microscopic Polyangiitis (MPA) • The aorta and renal, subclavian, and carotid
arteries are most commonly affected arteries.
Background • One of the most common causes of renovas-
• MPA is the second most common AAV in cular hypertension in children.
pediatrics.
• Kidneys and lungs are the most commonly Clinical Presentation
affected organs. • Variable symptoms of disease activity include
• Involves small arteries, veins, and fever, weight loss, myalgia, arthralgias, clau-
capillaries. dication, dizziness, headaches, visual distur-
bance, and abdominal pain.
Clinical Presentation • Carotidynia (pain and tenderness on palpation
• Lower respiratory tract involvement is over carotid bifurcation) is one of the most dis-
common. tinctive symptoms during the acute phase.
• Presents with hemoptysis or anemia sec- • The clinical manifestations depend on the
ondary to chronic, low-grade pulmonary phase of disease:
hemorrhage with pulmonary hemosiderosis –– Early phase has inflammation with nonspe-
or as catastrophic pulmonary hemorrhage. cific systemic symptoms lasting for weeks
• No pediatric-specific MPA criteria. or months. Diagnosis is challenging.
15 Rheumatology 545
–– Recurrent disease often occurs in new arte- • Biologic use has greatly improved outcomes
rial territories, with the coexistence of in comparison to nonbiologic therapies.
active and inactive lesions. • Mortality related to complications, including
–– The late, chronic phase (the “pulseless” arterial dissection, aortic rupture, uncontrollable
stage) is characterized by ischemia hypertension, cardiomyopathy, myocardial
and symptoms secondary to arterial infarction, renal failure, and infection.
occlusion. • High rate of relapse is common.
• Coexistence of IBD, pyoderma gangrenosum,
ankylosing spondylitis, and JIA has been
reported. Henoch-Schönlein Purpura (HSP)
• No specific laboratory tests or biomarkers. • The most common systemic vasculitis of
• WBC, platelet, ESR, and CRP levels are often childhood.
elevated at presentation or during disease • Characterized by palpable purpura, abdomi-
flare. nal pain, arthritis, and occasional kidney
• Fibrinogen may be elevated. involvement.
• Normocytic, normochromic anemia may be • HSP is a small-vessel leukocytoclastic vascu-
present. litis, also known as immunoglobulin A (IgA)
• Imaging helps confirm the diagnosis: vasculitis.
–– Conventional angiography, CT, MR angio- • IgA deposition is found in the vascular walls
grams, and Doppler ultrasound. in histologic studies.
–– Positron emission tomography (PET) scans • Annual incidence of approximately 20 per
are helpful for early assessment of 100,000 children.
inflammation. • Peak age of onset is between 4 and 6 years of
age.
Treatment • More common in boys than girls and more
• Corticosteroids. severe in adults than children.
• Induction and maintenance therapy, includ- • Seasonal variation has been noted in winter
ing methotrexate, azathioprine, and myco- and spring.
phenolate mofetil. • Possible infectious triggers have been impli-
• Cyclophosphamide has been utilized for life- cated including group A β-hemolytic strepto-
threatening or organ-threatening disease. coccus, Staphylococcus aureus, influenza,
• Biologic therapies have been used: etaner- parainfluenza, Epstein- Barr virus, adenovi-
cept, adalimumab, infliximab, tocilizumab, rus, parvovirus, and mycoplasma.
and rituximab.
• Blood pressure control is often necessary. Clinical Presentation
• Vascular surgery is needed for severe vessel • Purpura (Fig. 15.2):
damage. –– Palpable non-thrombocytopenic, purpuric
• Aortic valve replacement is necessary with rash is observed in 100% of cases and is
severe aortic regurgitation. generally the presenting symptom.
–– Rash involves gravity and pressure-depen-
Prognosis dent areas such as the buttocks and lower
• Early diagnosis and treatment improve mor- extremities. Less commonly, the face, ears,
bidity and mortality. and arms may also be involved.
–– Bowel ischemia, infarction, fistula forma-

tion, and intestinal perforation may occur
due to vasculitis.
• Nephritis:
–– Renal involvement is the main cause of late
morbidity and mortality in children with HSP.
–– Renal involvement usually occurs by week
6 but may occur 6 months from onset of
diagnosis.
–– 20% to 60% of children have kidney involve-
ment with microscopic hematuria and/or
proteinuria, but nephrotic-range proteinuria
and renal failure are possible.
Fig. 15.2 15-year-old male with Henoch-Schönlein pur- –– Hypertension.
pura. Note the dusky deep-red macules of varying diameters
Other, Less Common Features
–– Rash may present as deep-red macules and • Seizures
progress to palpable purpura and, less com- • Stroke
monly, hemorrhagic bullae or necrotic • Guillain-Barré syndrome
lesions. • Parotitis
–– Comes in crops; as one crop fades, another • Pulmonary hemorrhage
occurs.
–– Subcutaneous edema involving the scalp, Treatment
periorbital area, dorsa of hands and feet, • Supportive care is recommended.
and scrotum may occur early on, especially • Pain medications for abdominal and joint dis-
in the young. comfort are helpful, but NSAIDs may exacer-
• Arthritis: bate GI symptoms and renal issues if
–– Affects 50–80% of patients and associated present.
with joint pain, swelling, and possibly dif- • Antihypertensive therapy for persistent
ficulty with ambulation. hypertension may be indicated.
–– The joint swelling is periarticular and • The role of glucocorticoid treatment is con-
nondestructive. troversial but appears to shorten duration of
–– Knees and ankles are most commonly GI and joint involvement.
involved joints. • Corticosteroids, when started early, increase
• GI involvement: the odds of the abdominal pain resolving
–– GI involvement is noted in approximately within 24 h and may reduce the risk of
75% of children. intussusception.
–– In 20% of cases, GI symptoms precede the
Prognosis
rash by 2 weeks and may be confused with
• Follow-up with frequent urinalysis and blood
appendicitis.
pressure evaluations is recommended for
–– GI manifestations may include colicky
6 months.
abdominal pain, vomiting, diarrhea, GI
• The overall prognosis is good: 67% of chil-
bleeding, and intussusception. Pancreatitis
dren who have HSP run the course of the dis-
is rare.
ease within 4 weeks of onset.
–– Intussusception is usually ileo-ileal, occur-
• Recurrence affects about 25% of patients.
ring in up to 5% of patients.
15 Rheumatology 547
• Studies confirm that chronic renal insuffi- –– Vulvar ulcers often develop during the pre-
ciency and hypertension may develop up to menstrual stage of the cycle.
10 years after the initial onset of • Ocular involvement:
symptoms. –– Ocular lesions seen in 70–90%
• Typically, renal failure occurs in patients who –– Usually at presentation or within the first
present with acute glomerulonephritis and 2–3 years, rare after 5 years
have persistent nephrotic syndrome. –– Panuveitis (non-granulomatous)
• Overall, progression to end-stage renal fail- –– Conjunctivitis
ure is seen in a very small number of children –– Corneal ulceration
(1–5%) who have HSP. –– Papillitis
–– Retinal vasculitis
–– Hypopyon (up to 20%)
Behçet Disease • Arthritis
–– Seen in 40–50%.
Background –– Usually migratory, mono- or oligoarticu-
• A mixed vessel vasculitis that can affect any lar, and asymmetric.
size or type of vessel, predominantly the –– Most commonly affects the knees, ankles,
venous system elbows, and wrists.
• Characterized by painful recurrent orogenital –– Enthesopathy is common also, especially
ulcers, inflammatory eye disease, and joint in patients with acneiform lesions
and GI involvement –– Rare to have involvement of axial spine or
• Occurs equally in males and females small joints.
• Mean age of 30 years; rare in childhood, but –– Erosive changes are rare.
does occur –– Arthralgias are more common.
• Highest prevalence in Turkey and Japan • CNS involvement:
–– Frequency of 4–10%.
–– CNS involvement has two distinct forms,
• Aphthous ulcers:
which rarely co-exist:
–– Present in 97–100% of patients.
◦◦ Parenchymal disease (80%, poor
–– Initial manifestation in 25–75%.
prognosis)
–– Most come in crops (three-plus lesions),
◦◦ Dural sinus thrombosis (20%, favorable
< 1 cm, heal without scarring within
prognosis)
1–3 weeks, and are recurrent.
• Cutaneous lesions:
–– Ulcers preferentially appear on mucous
–– Papulopustular (acne) lesions (85%):
membranes of the lips, gingiva, buccal
◦◦ Indistinguishable from acne vulgaris
mucosa, and tongue and rarely on the pal-
◦◦ May occur in atypical locations
ate, tonsils, or posterior pharynx.
–– Nodular lesions (60%):
• Genital ulcers:
◦◦ Erythema nodosum-like lesions (more
–– Present in 80–90% of patients.
common in women), 50%
–– They are similar to those in the mouth and
◦◦ Superficial thrombophlebitis (associated
tend to be deeper, and 66% will leave scars
with major vessel involvement), 50%
after healing.
–– Pseudofolliculitis
–– Commonly appear on the scrotum or vulva.
–– Erythema multiforme
–– Less common on the penis and perianal
–– Pyoderma gangrenosum
and vaginal mucosa.
–– Nailfold capillary changes
• GI involvement: • Pathergy test:

–– Can be as high as 25–30%, especially in –– Pathergy is the hyperreactivity of the skin
the Japanese population to an intracutaneous injection or needle
–– Involves mucosal ulcerations in the ileum stick (frequently seen with blood draws).
and right side of the colon –– Rate of a positive reaction varies, but is
–– Risk of ileocecal perforation, which is the more common in Turkish and Japanese
third highest cause of mortality from populations (50%) and less common in
Behçet disease British/US populations.
• Vascular:
–– Major vessel occlusion/thrombosis Treatment
–– Aneurysm • Depends on organ involvement and severity
–– Pulmonary artery aneurysms: • Topical therapies:
◦◦ Unique complication of Behçet –– Sucralfate, lidocaine, or steroids
disease • Systemic therapies:
◦◦ The most frequent arterial complication –– Steroids, colchicine, anti-TNF agents, tha-
◦◦ Strongly associated with venous lidomide, dapsone.
thrombosis –– Azathioprine, methotrexate, or cyclosporine
has been useful in ocular Behçet disease.
Diagnosis –– No controlled studies on use of
• BD is a clinical diagnosis. anticoagulants.
• International Clinical Criteria for Behçet
Disease classification (1990) [7] states Prognosis
patients must present with the following: • Behçet disease is recurrent and
–– Recurrent oral ulcerations at least three unpredictable.
times in 1 year. Additionally, patients must • Male gender, early development of the dis-
present any two of the following: ease, and HLA-B51 gene positivity are mark-
◦◦ Recurrent genital ulcerations ers of poor prognosis.
◦◦ Eye lesions (uveitis or retinal vasculitis) • Eye disease, the most frequent cause of seri-
observed by an ophthalmologist ous morbidity, may lead to blindness in 20%
◦◦ Skin lesions (erythema nodosum, pseu- of those affected.
dofolliculitis, papulopustular lesions, • The disease may occasionally be fatal, with a
acneiform nodules) found in adult mortality rate of up to 6% due to vasculitis
patients not being treated with leading to arterial occlusion, ruptured arterial
corticosteroids aneurysms, pulmonary vasculitis, or involve-
◦◦ Positive pathergy test read by a physi- ment of the CNS.
cian within 24–48 h of testing • Death is associated with younger age, male
• ESR and CRP may be normal except during sex, arterial involvement, and a high number
active serositis, cerebral involvement, or of flares.
vasculitis.
• HLA-B51:
–– Three to six times more positivity in PEARLS AND PITFALLS
Eastern Mediterranean and Japanese
populations.
• JIA is a clinical diagnosis; there is no labora-
–– Positive test is associated with a more
tory test that makes the diagnosis.
severe clinical course.
15 Rheumatology 549
• JIA diagnosis is based on the chronicity of –– Rhabdomyolysis

arthritis (≥ 6 weeks duration). –– Mitochondrial myopathies
• JIA can be associated with normal labs –– Muscular dystrophies
including normal inflammatory markers, neg- • Growing pains are a diagnosis of exclusion
ative ANA, and negative RF; laboratory data based on a typical history and normal physi-
help to exclude other causes; laboratory test cal examination findings.
results are only supportive. • Joint pain associated with joint swelling is
• Any child diagnosed with JIA must be not a growing pain.
referred to a pediatric ophthalmologist for • Persistent joint or bone pain in a specific loca-
evaluation of uveitis periodically. tion must be investigated.
• JIA onset before 7 years of age with positive • The most common systemic vasculitis of
ANA is at the highest risk of developing uve- childhood is Henoch-Schönlein purpura
itis and will require more frequent screening (HSP); the classic presentations are palpable
by a pediatric ophthalmologist (every purpura, abdominal pain, arthritis, and occa-
3–4 months). sional kidney involvement (labs are usually
• HLA-B27 may be present or absent and is not normal).
required for diagnosis of enthesitis-related • A 6-month follow-up with frequent urinalysis
arthritis. and blood pressure evaluations is recom-
• An ANA may be positive in up to one-third of mended in all cases of HSP.
the healthy population and in family mem-
bers of patients with SLE.
• A negative ANA makes the diagnosis of SLE References
less likely.
• Post-streptococcal reactive arthritis (PSRA) 1. Wu E, Mater H, Radinovich CE, Juvenile idio-
is distinct from arthritis of acute rheumatic pathic arthritis In: Kliegman RM, Stanton BF,
fever (ARF); these patients do not meet crite- Schor NF, St. Geme III JW, Behrman RE, Nelson
ria for ARF. textbook of pediatrics, 19th Philadelphia:
• In cases of PSRA, secondary antibiotic pro- Elsevier Saunders; 2011. 830.
phylaxis against group A β-hemolytic strep- 2. Heiligenhaus A, Niewerth M, Ganser G,
tococcus (GAS) is recommended for 1 year if Heinz C, Minden K. Prevalence and compli-
there’s no evidence of carditis. cations of uveitis in juvenile idiopathic arthri-
• You must have the classic skin findings to tis in a population-based nationwide study
have a diagnosis of JDM. in Germany: suggested modification of the
• JDM can occasionally present with a normal current screening guidelines. Rheumatology.
CK and aldolase in patients who already have 2007;46:1015–9.
severe muscle atrophy. 3. Ardoin SP, Schanberg LE. Systemic lupus
• Polymyositis is exceptionally rare in pediat- Erythematosus. In: Kliegman RM, Stanton
rics, affecting an older age group than in BF, Schor NF, St. Geme III JW, Behrman RE,
JDM. editors. Nelson textbook of pediatrics. 19th
• Overlap myositis can be seen in lupus or ed. Philadelphia: Elsevier Saunders; 2011.
mixed connective tissue disease. p. 841.
• Don’t forget about other causes of myositis, 4. Hochberg MC. Updating the American College
including: of Rheumatology revised criteria for the clas-
–– Virus associated sification of systemic lupus erythematosus [let-
–– Strep-associated myositis ter]. Arthritis Rheum. 1997;40:1725.
5. Bohan A, Peter JB. Polymyositis and derma- vational cohort: PEDBD. Ann Rheum Dis.
tomyositis (first of two parts). N Engl J Med. 2016;75(6):958–64.
1975;292(7):344–7. Review. Koné-Paut I. Behçet's disease in children,
6. Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, an overview. Pediatr Rheumatol Online J.
Herlin T, Brik R, Paediatric Rheumatology 2016;14(1):10.
International Trials Organisation (PRINTO), Lee JY, Schneider R. Systemic juvenile
et al. EULAR/PRINTO/PRES criteria for idiopathic arthritis. Pediatr Clin N Am.
Henoch-Schönlein purpura, childhood polyar- 2018;65(4):691–709.
teritis nodosa, childhood Wegener granuloma- Ozen S, Pistorio A, Iusan SM, Bakkaloglu A,
tosis and childhood Takayasu arteritis: Ankara Herlin T, Brik R, Paediatric Rheumatology
2008. Part II: final classification criteria. Ann International Trials Organisation (PRINTO),
Rheum Dis. 2010;69(5):798–806. et al. EULAR/PRINTO/PRES criteria for
7. International Study Group for Behçet’s Disease. Henoch-Schönlein purpura, childhood polyar-
Criteria for diagnosis of Behçet’s disease. teritis nodosa, childhood Wegener granuloma-
Lancet. 1990;335(8697):1078–80. tosis and childhood Takayasu arteritis: Ankara
2008. Part II: final classification criteria. Ann
Rheum Dis. 2010;69(5):798–806.
Suggested Reading Petty RE, Laxer RM, Lindsley CB, Wedderburn L,
editors. Textbook of pediatric rheumatology. 7th
Amplified musculoskeletal pain syndrome. Center ed. Philadelphia: Elsevier; 2016.
for Amplified Musculoskeletal Pain Syndrome. Russo RAG, Katsicas MM. Takayasu arteritis.
Children’s Hospital of Philadelphia. https:// Front Pediatr. 2018;6:265.
www.chop.edu/conditions-diseases/ampli- Shenoi S. Juvenile idiopathic arthritis—changing
fied-musculoskeletal-pain-syndrome-amps. times, changing terms, changing treatments.
Accessed 14 Mar 2019. Pediatr Rev. 2017;38(5):221–32.
Bohan A, Peter JB. Polymyositis and dermato- Stanton BF. Pediatric rheumatology: a field of great
myositis (second of two parts). N Engl J Med. progress. Pediatr Clin N Am. 2018;65(4):xiii–xiv.
1975;292(8):403–7. Review. Tarvin SE, O'Neil K. Systemic lupus erythema-
Crayne CB, Beukelman T. Juvenile idiopathic tosus, Sjögren syndrome, and mixed connec-
arthritis oligoarthritis and polyarthritis. Pediatr tive tissue disease in children and adolescents.
Clin North Am. 2018;65(4):657–74. Pediatr Clin N Am. 2018;65(4):711–37.
Hashkes PJ, Toker O. Autoinflammatory Vehe RK, Riskalla MM. Collagen vascular dis-
syndromes. Pediatr Clin N Am. eases: SLE, dermatomyositis, scleroderma, and
2012;59(2):447–70. MCTD. Pediatr Rev. 2018;39(10):501–15.
Herman MJ, Martinek M. The limping child. Weiss PF. Pediatric vasculitis. Pediatr Clin N Am.
Pediatr Rev. 2015;36(5):184–97. 2012;59(2):407–23.
Higgins GC. Complications of treatments for pedi- Weiss PF, Colbert RA. Juvenile spondyloarthritis
atric rheumatic diseases. Pediatr Clin N Am. a distinct form of juvenile arthritis. Pediatr Clin
2018;65(4):827–54. North Am. 2018;65(4):675–90.
Koné-Paut I, Shahram F, Darce-Bello M, Cantarini West SG. Behçet disease and Cogan’s syndrome.
L, Cimaz R, Gattorno M, et al. PEDBD group. In: West SG, editor. Rheumatology secrets.
Consensus classification criteria for paediat- 3rd ed. Philadelphia: Elsevier Mosby; 2015.
ric Behçet's disease from a prospective obser- p. 248–52.
Neurology
16
Ivet Hartonian, Jong W. Yoo, and Jason T. Lerner
SEIZURES AND EPILEPSY • Simple febrile seizure

–– Brief generalized seizure
Classification of Seizure Types –– Less than 15 min
–– Does not recur within 24 h
• Simple partial (focal) seizures –– Febrile illness not involving the central
–– No impairment of consciousness nervous system (CNS)
–– Can have motor, sensory, or autonomic • Complex febrile seizure
features –– Can have focal features
–– Can evolve to a complex partial seizure –– Prolonged (> 15 min)
• Complex partial seizures (focal seizure with –– Recurs within 24 h of febrile illness
altered consciousness) • Evaluation
–– Impairment of consciousness –– Depends on clinical presentation
• Both simple and complex partial seizures can –– Ask about vaccination history
secondarily generalize –– Consider meningitis/encephalitis if child is
• Generalized seizures very sick; mental status changes, menin-
–– Absence (petit mal) geal signs, focal exam
–– Myoclonic –– Lumbar puncture if meningitis or encepha-
–– Clonic litis is suspected at any age
–– Tonic –– Strongly consider lumbar puncture in chil-
–– Tonic–clonic (grand mal) dren younger than 12 months because the
–– Atonic signs and symptoms of bacterial meningi-
tis may be minimal or absent in this age
group
Febrile Seizures –– Blood work for evaluation of the febrile ill-
ness, not the seizure
• Affects 2–5% of children –– Electroencephalogram (EEG) not neces-
• Most common childhood seizure type sary for simple febrile seizure
(6 months to 5 years) –– Neuroimaging is also not routinely needed
for simple febrile seizure
I. Hartonian
Pediatric Neurology, Department of Pediatrics, Adventist Health Management
White Memorial, Los Angeles, CA, USA
• Supportive
J. W. Yoo · J. T. Lerner (*)
Pediatric Neurology, Department of Pediatrics, UCLA Mattel • Treatment of underlying febrile illness
Children’s Hospital, Los Angeles, CA, USA
e-mail: jlerner@mednet.ucla.edu

552 I. Hartonian et al.
Prognosis Prognosis
• Approximately 1 in 3 patients will have recur- • The consequence of neonatal seizures is in
rence after experiencing first febrile seizure part dependent on the underlying etiology,
• Approximately 2–10% will likely be diag- response to treatment, and gestational age
nosed with epilepsy after experiencing a • There is higher mortality rate
febrile seizure • Depending on etiology, there can also be
increased risk of developing motor and cog-
nitive delays
Neonatal Seizures • “Fifth day fits” is a subset of benign familial
neonatal convulsions with seizures occurring
Background on the 5th or 6th day of life; self-limited
• Incidence of neonatal seizures in term infants
is 1–3.5 per 1000 births in the USA
• The incidence is much higher in preterm Infantile Spasms
infants
Background
Causes • Typical age of onset is between 4 and
• Hypoxic ischemic encephalopathy 7 months
• Intracranial hemorrhage (intraventricular, • Typically involve rapid flexion of the trunk,
subdural, subarachnoid) neck, and extremities, followed by a tonic phase
• Ischemic stroke • Often occur in clusters, and in between the
• Infections (meningitis) spasms, the child may cry
• Hypoglycemia • More common after an arousal, including
• Hypo or hypernatremia after a nap
• Hypocalcemia • West syndrome: Triad of infantile spasms,
• Hypomagnesemia hypsarrhythmia on EEG, and developmental
• Related to underlying inborn error of regression
metabolism
• Certain genetic disorders EEG—hypsarrhythmia
• Triad of: High amplitude, disorganized back-
Clinical presentation ground, multifocal discharges
• Often not obvious
• Subtle tonic or clonic movements of one limb Treatment
• Automatisms also possible (lip-smacking) • Adrenocorticotropic hormone (ACTH)
• Vigabatrin if the spasms are symptomatic in a
Diagnosis patient with tuberous sclerosis complex
• Laboratory evaluation to look for metabolic
abnormalities, hypoglycemia, or infection Prognosis
• EEG • If not treated early or effectively → increased
• Neuroimaging to look for underlying struc- risk of developmental delay and intellectual
tural abnormality disability
• Jitteriness can sometimes be associated with
hypoglycemia
Childhood Absence Epilepsy
Treatment
• Try to treat the underlying etiology such as Background
electrolyte abnormality or hypoglycemia • Typical onset between 4 and 10 years of age
• Phenobarbital • Staring and behavioral arrest
16 Neurology 553
• Can have eye blinking or eye flutter enign Epilepsy

B
• Automatisms with Centrotemporal Spikes (BECTS)
• Usually will last a few seconds with rapid
return to baseline Background
• Typically occur daily, multiple times per day • Previously known as benign rolandic epilepsy
• During brief episodes, there is memory lapse (BRE)
→ academic decline • Typical onset between 4 and 11 years of
• Often can be provoked with 2–3 min of age
hyperventilation • Simple focal motor seizures (mostly involv-
ing the face but can spread to arm and leg,
EEG and can also secondarily generalize)
• 3 Hz generalized spike-wave discharges • Can also have sensory features (paresthesias)
(Fig. 16.1) involving the corner of the mouth, cheek, or
tongue
Treatment
• There can be increased salivation and speech
• Ethosuximide
arrest
Prognosis • Majority of seizure events are nocturnal
• The majority will become seizure-free during • Patients typically have normal neurocogni-
adolescence tive development
Fig. 16.1 Generalized 3 Hz spike-wave discharges seen in childhood absence epilepsy
EEG ennox–Gastaut Syndrome

L
• Focal discharges in the centrotemporal (rolan-
dic) region with activation during sleep over a
normal background Background
• Often have multiple seizure types (tonic,
Treatment tonic–clonic, myoclonic, atypical absence,
• Low seizure frequency atonic “drop seizures”)
• Because seizures are typically nocturnal and • Seizures are often frequent and difficult to treat
infrequent, there is no absolute indication to • Begins in childhood
treat
• If treatment is considered, first-line is EEG
carbamazepine • Diffuse slow spike-and-wave discharges at
1.5–2.5 Hz (Fig. 16.2)
Prognosis
• May be associated with developmental delays Treatment
• Spontaneously remits in mid-adolescence • Usually requires multiple medications
• Consider ketogenic diet
• Surgical options
Juvenile Myoclonic Epilepsy • Consider corpus callosotomy in patients with
refractory drop seizures
Background • Vagal nerve stimulator placement
• Typical onset between 12 and 18 years of age
• Often presents with generalized tonic–clonic Prognosis
seizures • Refractory epilepsy
• Risk factors include sleep deprivation (from a • Intellectual disability
sleepover), stress, and alcohol use
• Will often report jerking movements (myo-
clonic seizures) of the upper extremities upon Landau–Kleffner Syndrome
awakening
Background
EEG • Onset between 3 and 7 years of age
• Generalized “atypical” spike or polyspike- • Acquired aphasia after development of nor-
and-wave discharges at 4–6 Hz mal language skills
• Photosensitivity is common • 25% of patients do not have clinical seizures
Treatment EEG
• Valproic acid • Spikes, sharps, and spike-and-wave discharges
• Risk of neural tube defects typically seen over bilateral temporal areas
• May consider lamotrigine or levetiracetam • Presence of electrical status epilepticus dur-
ing slow-wave sleep (ESES)
Prognosis • Continuous spike-wave discharges during
• Lifelong risk of seizures 85% of slow-wave sleep
16 Neurology 555
Fig. 16.2 Generalized 1 Hz slow spike-wave seen in Lennox–Gastaut syndrome
Treatment • Neuropathology possibly related to perivas-

• Anticonvulsants cular lymphocytic infiltrates (no clear expla-
• Corticosteroids nation why it is unilateral)
• Benzodiazepines • Anti-glutamate receptor antibodies have been
found in patients, suggesting an autoimmune
Prognosis process
• Often, clinical seizures have good response to • Medical treatment includes high-dose steroids
medications and intravenous immunoglobulin (IVIG)
• Language recovery is variable (only a temporary solution, as the process is
progressive)
• Definitive treatment is functional hemispher-
Rasmussen Encephalitis ectomy (disconnecting the affected cerebral
hemisphere)
• Progressive encephalopathy, often leading to
• Varying degrees of focal deficits are to be
refractory partial seizures, cognitive decline,
expected after hemispherectomy (hemipare-
and hemiparesis
sis, speech difficulties)
• Imaging shows eventual atrophy in the affected
cerebral hemisphere
Type of seizure and treatment of choice Status Epilepticus

(Table 16.1)
Common side effects of antiepileptic drugs Background
(Table 16.2) • Status epilepticus (SE) is defined as repeated
seizures without regaining consciousness
Table 16.1 Type of seizure and treatment of choice between attacks, or prolonged seizure for at
Seizure type Treatment of choice least 5 or 30 min (evidence is based on animal
Partial seizures Carbamazepine data and incomplete)
Oxcarbazepine • Although SE is seen throughout the life span,
Levetiracetam it tends to be more common in children under
Absence Ethosuximide
Valproic acid
1 year of age and adults older than 60 years
Lamotrigine • The etiology of SE is dependent on age group;
Generalized Valproic acid 50% of SE in children occurs with febrile ill-
tonic–clonic Levetiracetam ness; SE in this setting has a 5% mortality
Lamotrigine rate
Infantile spasms Adrenocorticotropic hormone
(ACTH)
Vigabatrin (tuberous sclerosis)
• SE can occur with multiple seizure types
• Generalized tonic–clonic (primary or second-
Table 16.2 Common side effects of antiepileptic drugs
ary generalization)
Antiepileptic drugs
(AEDs) Common side effects
• Myoclonic (often seen following anoxic brain
Ethosuximide Gastrointestinal upset injury)
Leukopenia • Tonic (primarily in children, especially those
Sedation with Lennox–Gastaut syndrome)
Carbamazepine Rash ➔ Stevens–Johnson • Clonic (primarily in children)
syndrome
Drug interaction (oral
• Epilepsia partialis continua (in cases of
contraceptives) Rasmussen encephalitis)
SIADH/hyponatremia • Absence
Leukopenia, hepatotoxicity
Teratogenicity Management
Dizziness/ataxia • Noninvasive airway protection (0–2 min)
Phenytoin Zero-order kinetics
Hirsutism, ataxia, gum
• Intubation if airway compromise, poor oxy-
hypertrophy, rash, teratogenic: genation, or increased intracranial pressure
fetal hydantoin syndrome (ICP) (0–10 min)
Phenobarbital Cognitive slowing • Vital signs assessment (0–2 min)
Commonly used in Behavioral changes • Vasopressor support if needed (5–15 min)
(neonates and infants)
Lamotrigine Rash • Neurologic exam (0–5 min)
Stevens–Johnson syndrome • IV access for meds and fluids (0–5 min)
Levetiracetam Irritability • Send blood (complete metabolic panel, com-
Behavioral changes plete blood count, calcium, magnesium; con-
Hyperactivity
sider toxicology screen and antiepileptic drug
Valproic acid Weight gain
Tremor levels)
Hair loss • Check finger-stick glucose (0–2 min)
Hepatotoxicity • Start IV fluids
Pancreatitis • In adults, give thiamine before giving glucose
Teratogenicity
All AEDs Suicidal ideation (literature is not
if there is hypoglycemia
clear) • 3 equivalent first-line options:
SIADH Syndrome of inappropriate antidiuretic hormone –– Intramuscular (IM) midazolam
secretion
16 Neurology 557
–– IV lorazepam • Cardiovascular: Tachycardia, cardiac

–– IV diazepam arrhythmia
• If seizures persist, second therapy options: • Renal: Acute renal insufficiency, myoglobin-
–– IV fosphenytoin uria, or rhabdomyolysis
–– IV valproic acid • Autonomic: Hyperthermia
–– IV levetiracetam • Metabolic: Lactic acidosis, electrolyte
• If none of the above are available, IV disturbances
phenobarbital
• If seizures continue, choices include (no clear Prognosis
evidence for one therapy over another): • Early mortality from SE in children is 3%
–– Continuous infusion of thiopental, mid- • Longer duration of SE is associated with
azolam, pentobarbital, or propofol worse outcome
• With any of the above, the patient should be • Etiology of SE is also related to prognosis
on continuous EEG monitoring
• Admit patient to intensive care unit Keywords of high yield cases of epilepsy syn-
• Urgent EEG or, if possible, continuous EEG dromes (Table 16.3)
monitoring if patient is not waking up after
Clinical approach to first-time seizure
clinical seizures have stopped
• It is estimated that in the USA, between
• Additional evaluations once patient is stable
25,000 and 40,000 children per year have a
can include lumbar puncture if patient is
first unprovoked seizure
febrile or infection is suspected, as well as
• First nonfebrile seizure without obvious pro-
neuroimaging
voking factors (head trauma, intracranial
Complications from SE infection, or tumor)
• Neurologic: Neuronal damage, elevated ICP, • Immediate evaluation: Stabilize the child, and
cerebral edema obtain detailed history to determine if seizure
• Respiratory: Hypoxia, aspiration, hypercapnia has occurred and if it is the child’s first seizure
Table 16.3 Keywords of high-yield cases of epilepsy syndromes

Keywords Epilepsy syndromes
Infant with rapid repetitive clusters of seizures or head nodding, West syndrome
hypsarrhythmia on EEG, and neurodevelopmental arrest/regression
Behavioral arrest, staring, eye flutter, automatisms, lack of a postictal state, Childhood absence epilepsy
3 Hz spike-wave discharges on EEG (4–10 years of age)
Seizures soon after sleep onset or just before awakening, paresthesia of the Rolandic epilepsy with centrotemporal
mouth/tongue, facial twitching, and drooling (onset 4–11 years) spikes
Ictal vomiting, eye deviation, convulsions less common, events often Panayiotopoulos syndrome
prolonged (> 5 min) (onset 3–6 years)
Myoclonic seizures (jerks) involving the upper extremities upon Juvenile myoclonic epilepsy
awakening, GTCs, sensitive to sleep deprivation, EEG 4–6 Hz (spike and
polyspike-wave)
Language regression or acquired aphasia after normal language Landau–Kleffner syndrome
development + electrographic status epilepticus in sleep (ESES) “Acquired epileptic aphasia”
Intractable epilepsy, multiple seizure types, intellectual disability, slow Lennox–Gastaut syndrome
spike-wave EEG < 3 Hz
Progressive partial seizure, difficult to treat, positive antibodies, atrophic Rasmussen’s encephalitis
hemisphere
Gelastic seizures: sudden burst of mirthless laughter, cooing, giggling, or Hypothalamic hamartoma
smiling
GTC generalized tonic–clonic seizure, EEG electroencephalogram
• Laboratory evaluation should be based on • Cyanotic breath-holding episodes often

individual clinical history such as vomiting, triggered by emotional stimuli (anger, frus-
diarrhea, and dehydration tration); the breath- holding occurs in
• Toxicology screen if any concern of drug expiration
exposure or substance abuse • Pallid breath-holding episodes often pro-
• Lumbar puncture has limited value unless voked by sudden fear (after injury, surprise)
there is concern for meningitis or • With both spells, there can be loss of con-
encephalitis sciousness followed by limpness and move-
• EEG is recommended to help determine sei- ments that can look similar to tonic posturing
zure type, epilepsy syndrome, and risk for or myoclonic jerks
recurrence • By age 6, most children will no longer have
• Emergent neuroimaging should be performed episodes
in children with postictal focal deficits or pro- • Iron deficiency anemia is highly associated
longed altered mental status. Magnetic reso- with breath-holding spells. Check complete
nance imaging (MRI) is the preferred imaging blood count and ferritin. Supplement if
modality in children necessary
• Risk of seizure recurrence is higher in indi-
viduals with remote symptomatic etiology Sandifer syndrome
(history of head trauma or cerebral palsy) and • Involves tonic neck extension and dystonic
abnormal EEG posturing of trunk
• Treatment with antiepileptic drugs (AED) • Commonly associated with gastroesophageal
after first seizure compared to second seizure reflux disease (GERD)
has not been shown to impact prognosis for • The posturing is believed to be related to the
long-term seizure remission discomfort from reflux
• Treatment with AED may be considered • Infants typically have normal neurologic
based on individual circumstances where the exam, and clinical history reveals a relation-
benefit of preventing a second seizure out- ship between feeding and the posturing
weighs the risks of AED side effects
Syncope
Neurodiagnostic studies of choice • Definition: Brief loss of consciousness as
• Head ultrasound—Preterm periventricular well as postural tone secondary to a transient
hemorrhagic infarction (although MRI more decrease in cerebral perfusion with rapid
sensitive) recovery back to baseline
• Computed tomography (CT)—Skull fracture, • Most common etiology of syncope is neuro-
epidural hematoma, subdural hematoma cardiogenic (vasovagal)
• MRI—Diffuse axonal injury, subarachnoid • Cardiovascular-mediated syncope includes
hemorrhage, child abuse, hypoxic–ischemic arrhythmias (supraventricular tachycardia)
encephalopathy, developmental brain malfor- and cardiac structural problems (aortic
mations, stroke stenosis)
• If patient has recurrent syncope, family his-
tory of syncope, or sudden unexplained death,
Epilepsy Mimics then cardiology referral is indicated
Breath-holding spells Night terrors

• Typical age of onset is between 6 and 18 • Non-rapid eye movement disorder
months • A type of parasomnia
16 Neurology 559
• Most commonly occur in the first one-third of • Distinctive bony lesion (sphenoid dysplasia,
the night thinning of long bone cortex)
• Clinically can see facial flushing and agitation • Optic nerve glioma
• Child will have amnesia for the event • First-degree relative with NF1
• Night terrors can occur throughout first
decade of life and usually will spontaneously Common associations
remit • Learning disabilities
• Migraines
Movement disorders • Seizures
• The movements associated with various move- • Skeletal abnormalities: Scoliosis, short
ment disorders can be perceived as epileptic in stature
nature
• Examples include tic disorder, sleep myoclo- Increased risk
nus, and paroxysmal dyskinesia • Pilocytic astrocytoma
• Meningioma
• Leukemia
NEUROCUTANEOUS
Treatment
DISORDERS • Genetic counseling
• Early detection of malignancies
Neurofibromatosis Type 1 • Prevention of future complications
Genetics
• Autosomal dominant
Neurofibromatosis Type II
• Chromosome 17
• Most common with incidence of 1/3000 Genetics
• Childhood onset • Autosomal dominant
• Chromosome 22
Diagnosis made by 2 or more of the following:
• Incidence of 1/40,000
(Table 16.4)
• Onset in adolescence
• > 6 café au lait spots: 5 mm prepubertal and
15 mm in pubertal children (hallmark of NF1) Diagnosis with one of the following:
• Axillary or inguinal freckling • Bilateral vestibular schwannomas (cranial
• 2 neurofibromas or > 1 plexiform nerve [CN] VIII)
neurofibroma • First-degree relative with NF2 and unilateral
vestibular schwannoma
Table 16.4 Age of onset of major clinical manifestations of • Any 2 of the following: meningioma, schwan-
neurofibromatosis 1 noma, neurofibroma, glioma, or subcapsular
Clinical finding in NF1 Age of onset cataracts
Café au lait spots Birth to 12 years
Axillary or inguinal 3 years to adolescence Common associations
freckling • Hearing loss
Lisch nodules > 3 years
• Tinnitus
Optic glioma Birth to 7 years (up to
30 years) • Gait abnormalities
Cutaneous neurofibromas > 7 years (usually late
adolescence) Increased risk
Plexiform neurofibromas Birth to 18 years • Multiple inherited schwannomas
• Meningioma Common associations

• Ependymoma • Seizures (most common presenting symptom)
• Infantile spasms
Treatment • Intellectual disability
• Genetic counseling
• Annual hearing screen Increased risk
• Early detection of malignancies • Rhabdomyomas found in 50% of cases may
spontaneously regress or may lead to conges-
tive heart failure
Tuberous Sclerosis • Angiomyolipomas can lead to spontaneous
pneumothorax
Genetics • Polycystic kidney disease
• Autosomal dominant • Intellectual disability when presenting with
• Chromosome 9 and 16 severe seizures
• 1/6000 live births
• 50% may be spontaneous mutations Treatment
• Seizure control
Diagnosis/findings • Echocardiogram (ECHO)
• Ash leaf spots (Fig. 16.3a) • Blood pressure check/renal ultrasound
• Shagreen patch • Neuroimaging every 1–3 years
• Periungual fibromas • CT chest in adolescent females
• Facial angiofibromas (Fig. 16.3b)
• Cardiac rhabdomyoma
• Renal and pulmonary angiomyolipomas turge–Weber Syndrome
S
• Cortical tubers
• Subependymal giant cell astrocytomas Genetics
(SEGA) • Spontaneous mutation
• Minor features: Dental pits, rectal polyps, • Incidence of 1/50,000
bone cysts, “confetti” skin lesions, white
matter radial migration lines, gingival fibro- Diagnosis/findings
mas, nonrenal hamartomas, multiple renal • Facial port-wine stain in V1 or V2 distribution
cysts • Seizures
a b
Fig. 16.3 (a) Typical ash leaf macules: Hypomelanotic (adenoma sebaceum): Multiple papular lesions varying in
macules round and oval in shape and vary in size from a few size clustered on and around the nose and cheeks
mm to as much as few cm in length. (b) Facial angiofibromas
16 Neurology 561
• Ipsilateral cerebral leptomeningeal angioma • Unilateral (frontal/temporal) location (may

which calcifies over time (tram-track/railroad be bilateral in children)
calcifications on CT) • Typically has a pulsating quality
• Nausea and/or vomiting
Common associations • Photophobia and/or phonophobia
• Intellectual disability • Vertigo
• Seizures • May have associated aura
• Contralateral hemiparesis and hemianopia • Child will typically seek a quiet and dark
place to rest
Increased risk • Sleep can often relieve the pain
• Glaucoma • Periodic syndromes in children such as cyclic
• Seizures vomiting (recurrent bouts of vomiting) or
• Hemiparesis benign paroxysmal vertigo (recurrent epi-
• Hemiatrophy sodes of dizziness) often become typical
migraines as child gets older
Treatment
• Seizure control—may require hemispherectomy Features of aura
• Annual eye screening • Fully reversible visual symptoms
• Flickering lights, spots, lines, and even loss
of vision
HEADACHE • Fully reversible sensory symptoms—pins
and needles or numbness
Epidemiology • Fully reversible dysphasic speech disturbance
• Prevalence of headache in children up to the • Aura symptoms develop over ≥ 5 min
age of 20 years is approximately 58% • Each symptom typically lasts ≥ 5 min and
• Female:male ratio of 1.5:1 in this same age ≤ 60 min
group • Headache typically develops during the aura
• Migraines in this population are seen 7.7– or follows aura within 60 min
7.9% in females and 6% in males
• In young children, boys have more migraines,
but this reverses at puberty Tension Headache
• Younger children often have more atypical
symptoms • Milder headache
• Less disabling than migraine headaches
Types of headaches • Usually, there is no nausea or vomiting
• Migraine • Can have either photophobia or phonophobia
• Tension but usually do not have both
• Chronic nonprogressive • Pain often described as “band-like” around
• Chronic progressive the head
• Often responsive to over-the-counter analgesics
Migraine Headache
Chronic Nonprogressive Headache
• Acute intermittent headache • Also called new daily persistent headache
• Duration of pain can be 30–60 min but up to 72 h • Definition: Headache present for ≥ 4 months
for ≥ 15 days/month
• Common in adolescents Diagnosis of Primary Headache

• Usually, there is a normal neurologic exam Syndromes
• Often, there are psychosocial factors involved
• Clinical history
Treatment –– Ask about family history of headaches
• Multidisciplinary approach is best –– Impact on school (days missed, drop in
• Pharmacologic interventions (preventative grades)
treatment such as amitriptyline) –– Ask about anxiety, depression, other psy-
• Lifestyle modifications (adequate sleep, mod- chiatric comorbidities
erate exercise, regular meals) –– Ask about extracurricular activities
• Biobehavioral strategies (relaxation • Imaging
exercises) –– Low-yield imaging in an isolated head-
• Psychiatric and/or psychological interventions ache unaccompanied by other neurologi-
cal findings
–– CT only indicated in acute cases such
Chronic Progressive Headache as high suspicion for subarachnoid
• Gradual increase in frequency of headache hemorrhage
• Gradual increase in severity of headache – – MRI indicated for chronic progressive
• Consider the presence of increasing ICP headache, even in absence of focal
• Differential diagnosis includes brain tumor, neurologic symptoms
hydrocephalus, chronic meningitis, brain • Typically no indication for EEG or skull films
abscess, subdural hematoma, and idiopathic • No routine blood work
intracranial hypertension (pseudotumor cerebri)
reatment of Primary Headache
T
Headache “Red Flags” Syndromes
Clinical presentation General

• Sudden severe headache • Lifestyle modifications (regular meals, con-
• Occipital headache sistent sleep, exercise, hydration)
• Early morning headache • Methods to cope with stress
• Pain that awakens the child from sleep • Treat pain early
• Worsening of pain with changes in position • Set realistic goals
• Increasing frequency and intensity of
Acute treatment
headache
• Acetaminophen
Physical exam • Ibuprofen, naproxen, and other NSAIDs
• Change in mental status • Triptans (only rizatriptan and almotriptan are
• Cranial nerve palsies approved by the US Food and Drug
• Visual field defects Administration for pediatrics)
• Papilledema • Consider promotility agents, as gastroparesis
• Abnormal pupillary responses can delay medication absorption (prochlor-
• Focal neurologic deficits perazine, metoclopramide)
• Ataxia, gait disturbance
16 Neurology 563
Chronic treatment (preventative therapy) Treatment

• Lifestyle change • Abortive medications: NSAIDs; triptans if
• Exercise, regular sleep pattern, good balanced posttraumatic headaches have migraine fea-
diet, hydration tures; opioids should be avoided
• Avoid overuse of analgesic medications; may • Preventive treatments: Lifestyle modifica-
cause analgesic headache tions; typical prophylactic medications used
• Try to use medications that will address to treat primary headaches (riboflavin, mag-
comorbidities nesium, amitriptyline, topiramate, proprano-
• Amitriptyline for patients with sleep problems lol); comorbid symptoms should also be
• Cyproheptadine for patients with allergies, addressed (psychiatric conditions, sleep prob-
poor appetite, or thin lems, cognitive issues)
• Topiramate for obese patients
• Avoid propranolol in patients with asthma
Idiopathic Intracranial Hypertension
Alternative therapies
• Behavioral therapies (biofeedback) Background
• Acupuncture • Previously called pseudotumor cerebri
• Natural supplements (magnesium, riboflavin, • Important consideration in the differential
butterbur) diagnosis in a patient with chronic daily
headache
• Incidence of 3.5–19 per 100,000
Posttraumatic or Postconcussion • Majority of patients are female
Headaches
Clinical features (Table 16.5)
• Posttraumatic headache is common in asso- • Will often have diffuse pounding headache
ciation with other postconcussive symptoms • Can also complain of neck stiffness and tran-
such as dizziness, sleep disturbance, and sient visual disturbances
mood changes • Key features of exam include papilledema
and visual field testing to evaluate for an
Risk factors for posttraumatic headache enlarged blind spot
• Preexisting headache (migraine) • Neuroimaging is often normal (CT scan must
• Age (adolescence) be performed before lumbar puncture)
• Psychological factors (maladaptive coping • Diagnostic approach includes basic cerebro-
strategies, high-risk psychological traits) spinal fluid (CSF) evaluation plus obtaining
opening pressure during lumbar puncture
Assessment (pressure will exceed 200 mm H2O)
• Thorough history and neurologic exam
• Ask about preexisting headaches
• Ask about frequency, severity, and character- Table 16.5 Signs of increased intracranial pressure accord-
istics of posttraumatic headaches as well as ing to age
other postconcussion symptoms Age Signs of increased intracranial pressure
• Laboratory evaluation usually not indicated Infants Poor oral intake, irritability, wide sutures,
unless there is concern for other underlying bulging fontanel, downward deviation of eyes,
condition (hypothyroidism, anemia) hydrocephalus
Children Headache, diplopia, papilledema, abducens
• Neuroimaging (CT or MRI) is typically not nerve paralysis, hypertension, and bradycardia
indicated if neurologic exam is normal
• Lumbar puncture will also often help with Symptoms

headache symptoms by relieving the • Generally asymptomatic in early childhood.
pressure During adolescence or adult life can cause recur-
rent headaches, urinary frequency, neck pain,
Treatment and progressive lower extremity spasticity
• Carbonic anhydrase inhibitors such as
acetazolamide Treatment
• Ophthalmological follow-up if visual symp- • Asymptomatic patients can be monitored
toms are prominent clinically and with MRI to evaluate progress
• If necessary, optic nerve sheath fenestration as needed. Symptomatic patients can undergo
can be performed surgery as necessary
Arnold–Chiari Malformation Type II

MALFORMATIONS
Definition
OF THE BRAIN • Classic form of Chiari malformation.
Cerebellar tonsillar and lower medullary her-
Arnold–Chiari Malformation niation through the foramen magnum into the
Type I (Table 16.6) upper cervical canal. Associated with pro-
gressive hydrocephalus due to obstruction of
Definition
outflow of CSF through the posterior fossa
• Most common type of Chiari malformation.
and lumbosacral meningomyelocele
Herniation of the cerebellar tonsils through
the foramen magnum into the cervical canal Symptoms
can be associated with syringomyelia but is • Some can present in infancy with dysphagia,
not associated with hydrocephalus stridor, apnea, and weak cry. Can also present
later with gait abnormalities and incoordination
Table 16.6 Difference between Chiari malformation type I and type II

Chiari malformation type I Chiari malformation type II
Herniation of the cerebellar tonsils > 0.5 cm below the Herniation of cerebellar tonsils and lower medulla, pons, fourth
foramen magnum into the cervical canal ventricle through the foramen magnum into the upper cervical
canal
Most common and least severe Less common and more severe
Can involve the cranial nerve
Can be associated with syringomyelia (Spine MRI is Usually associated with hydrocephalus, and myelomeningocele
diagnostic)
Asymptomatic during childhood Infants
During adolescence Dysphagia
Neck pain Apnea
Recurrent headaches Weak cry
Sleep apnea Older children
Bowel/bladder dysfunction Gait abnormalities
Lower extremities spasticity
Observation Observation
Surgical decompression as necessary Serial MRI follow-up
Surgical decompression as necessary
MRI magnetic resonance imaging
16 Neurology 565
Treatment genesis of Corpus Callosum

A
• Clinical observation and serial MRIs to eval-
uate for any progression. Surgical decom- Definition
pression as necessary • Complete or partial, depending on the stage
of development at which growth was arrested
• Isolated, incidental finding in some patients
Lissencephaly • When accompanied by other malformations,
can result in severe seizures and intellectual
Definition disability
• Smooth brain without sulci. (Agyria refers to • Chromosomal mutations (8, 9, 13, 18), inborn
portions of the brain lacking gyri; pachygyria errors of metabolism (nonketotic hypergly-
refers to the presence of broad gyri and shal- cinemia, neonatal adrenoleukodystrophy,
low sulci) pyruvate dehydrogenase deficiency), and
• Caused by incomplete or failure of neuronal teratogens (maternal alcohol and cocaine use)
migration, resulting in a lack of development
of gyri and sulci Symptoms/exam
• Type 1 is associated with facial dysmor- • Intellectual disability, seizures, hypo- or
phism and sometimes with deletion of chro- hypertelorism
mosome 17 • Aicardi syndrome: Combination of agenesis
• Type 2 is associated with hydrocephaly and of corpus callosum, chorioretinal lacunae,
dysgenesis of the cerebellum and infantile spasms
• Recurrent hypothermia (Shapiro syndrome)
Symptoms/exam • Development can be normal if it is the only
• Microcephaly, results in neurologic neurologic manifestation
impairment
Diagnosis/treatment
Diagnosis/treatment • MRI brain, supportive care, and treatment of
• CT or MRI of brain, supportive care neurologic sequelae
Polymicrogyria Dandy–Walker Malformation

Definition Definition
• Presence of large number of small gyral con- • Cystic expansion of the fourth ventricle in the
volutions separated by shallow sulci. Usually posterior fossa. Majority of cases have
an acquired defect hydrocephalus
• Malformation is also often associated with
agenesis of corpus callosum and agenesis or
• Depends on location, extent, and severity.
hypoplasia of cerebellar vermis
Seizures are common sequelae
Symptoms/diagnosis
Diagnosis/treatment
• Wide range of neurodevelopmental outcomes.
• CT or MRI of the brain, supportive care, and
Can see rapid increase in head circumference
treatment of seizures
and prominent occiput due to hydrocephalus,
cerebellar ataxia, delayed motor, and cogni- M acrocephaly

tive development. Can also be associated with
orofacial deformities and with congenital Definition
abnormalities of the cerebrovascular, gastro- • Head circumference > 2 standard deviations
intestinal, and genitourinary systems above the mean for age and gender; megalen-
• MRI of the brain shows cystic structure in cephaly (large brain)
posterior fossa
Etiology
Treatment • Familial
• VP shunt for hydrocephalus, treatment of • Sporadic
neurologic sequelae • Associated with neurofibromatosis, tuberous
sclerosis, or achondroplasia
• Certain metabolic disorders (Alexander dis-
DISORDERS OF HEAD GROWTH ease, Canavan disease, Soto syndrome)
Microcephaly Diagnosis
• Ask about family history
Definition
• Check for evidence of increased ICP
• Head circumference > 2 standard deviations
• If concern for elevated ICP → neuroimaging
below the mean for age and gender
Treatment
Etiology
• Treat underlying etiology
• Primary—genetic syndromes, chromosomal
• Monitor development and refer to appropriate
abnormalities (trisomy 13, 18, 21)
services if indicated
• Secondary (acquired)
–– Intrauterine infection—TORCH which
includes Toxoplasmosis, Other (syphilis,
varicella-zoster, parvovirus B19), Rubella, H
ydrocephalus
Cytomegalovirus (CMV), and Herpes
infections Definition
–– Postnatal infections—meningitis, enceph- • Disturbance of formation, flow, or absorption
alitis of CSF that leads to an increase in volume
–– Hypoxic ischemic encephalopathy within the cerebral ventricles and an elevation
–– Stroke in ICP
–– Traumatic brain injury
–– Malnutrition
Ventricular system (CSF flow)
Diagnosis • Unilateral flow
• Ask about family history • CSF is mostly made in choroid plexus within
• Obtain TORCH titers ventricles (total volume produced is about
• Consider karyotype 400–500 mL/day)
• Neuroimaging • CSF flows from lateral ventricles → foramina
of Monro → third ventricle → cerebral aque-
Treatment duct → fourth ventricle → foramina of
• Genetic counseling Luschka and foramen of Magendie → cis-
• Monitor for developmental delays (refer for terna magna → reabsorbed in the arachnoid
appropriate interventions such as physical, granulations
occupational, and speech therapy)
16 Neurology 567
Obstructive (noncommunicating) hydrocephalus –– Shunt malfunction (headache without

• CSF is obstructed within the ventricular sys- fever)
tem or in its outlets to the arachnoid ◦◦ Consult neurosurgery for shunt
granulations adjustment
• Most common etiology is congenital aque- –– Epilepsy: Occurs in 1/3 patients 10 years
ductal stenosis post-shunt
• Other causes include posterior fossa tumors, ◦◦ Subacute/chronic shunt dysfunction can
Arnold–Chiari type II malformations, and occasionally present with worsening sei-
Dandy–Walker syndrome zures or status epilepticus
Nonobstructive (communicating) hydrocephalus

• Flow within ventricular system is intact, but C raniosynostosis
the cisterns and arachnoid villi cannot absorb
CSF Definition
• Typically related to accumulation of blood or • Premature fusion of one or more sutures →
infectious material abnormal skull shape
• Causes include subarachnoid hemorrhage, • Incidence is about 3.4 per 10,000 births
intraventricular hemorrhage (premature • Most common is closure of sagittal suture
infants), and meningitis (50–60%)
Clinical features Etiology

• Signs and symptoms of increased ICP • Typically sporadic
• Altered mental status, irritability • Secondary causes
• In infants: Full fontanel, rapid head growth, –– Certain metabolic disorders (hyperthy-
poor feeding, downward deviation of eyes roidism)
(sunset sign) –– Storage disease (mucopolysaccharidosis)
• Vomiting –– Genetic disorders (Crouzon, Apert, and
• Headache Pfeiffer syndromes)
• Increased tone or reflexes –– Hematological disorders (thalassemia)
–– Brain malformations (holoprosencephaly,
Diagnosis microcephaly)
• Consider head ultrasound in infants (through –– Teratogen exposure (valproic acid)
the anterior fontanel)
• Head CT or MRI Diagnosis
• Palpation of skull
Treatment • Skull films
• If possible, treat underlying etiology • Head CT if considering surgery
• Medical treatment with acetazolamide
• Definitive treatment is surgical with place- Treatment
ment of ventriculoperitoneal (VP) shunt • Surgery in moderate to severe cases to restore
• Shunt complications normal skull/facial growth and development
–– Infection (persistent fever, headache) • Surgical intervention is mandatory if there is
◦◦ Antibiotic and shunt replacement increased ICP
VASCULAR ANOMALIES • Neurosurgical intervention may be needed in

cases of hemorrhagic stroke
Stroke
Prognosis
Background • Mortality rates are higher with hemorrhagic
• Incidence is about 2–3 per 100,000 children stroke compared to ischemic stroke, but long-
annually term comorbidities are less common with
• About 1 infant in 4,000 live births hemorrhagic stroke
• There is low recurrence rate after neonatal
Causes stroke
• Ischemic stroke includes congenital heart dis-
ease, coagulation disorders, infections (men-
ingitis), sickle cell disease, vasculopathies, Arteriovenous Malformations
and arterial dissection (AVMS)
• Hemorrhagic stroke includes congenital vas-
cular anomalies (arteriovenous malforma- • Result from failure of normal capillary bed
tions), brain tumors, head trauma, and development between cerebral arteries and
thrombocytopenia veins
• Most are sporadic and isolated
Clinical presentation • Tend to cause supratentorial intracranial
• Acute onset of hemiparesis hemorrhages
• Seizures • Patients can present with sudden headache,
• Severe headache with focal neurologic symp- seizures, and focal neurologic deficits if an
toms most commonly present in hemorrhagic AVM bleeds
stroke • CT will show acute blood
• Additional signs and symptoms include irri- • Conventional angiography will provide a
tability, lethargy, and behavioral changes more detailed assessment of the AVM
• Surgical treatment often required given high
Diagnosis recurrence rate
• Neuroimaging
–– CT is good in cases of hemorrhagic stroke
(acute blood) Vein of Galen Malformation
–– MRI/magnetic resonance angiography,
including diffusion-weighted imaging is • Arteriovenous shunt between cerebral arter-
more sensitive for ischemic stroke ies and the vein of Galen
–– Conventional angiography is the gold stan- • Typically presents in neonatal period with
dard if noninvasive evaluation is inconclusive high-output congestive heart failure
–– Consider Echo and hypercoagulable • There can also be progressive macrocephaly
evaluation from hydrocephalus due to increasing venous
pressure
Treatment • Diagnose with neuroimaging
• Treat the underlying etiology • Treatment includes management of heart fail-
• Aspirin is the main antiplatelet agent used in ure and embolization
children
16 Neurology 569
Cerebral Venous Thrombosis • As the child grows, the distal part of the spinal
cord is stretched and can become ischemic
Background
• Incidence of about 1 in 100,000 children Clinical features
annually • Cutaneous lesion in lower back (tuft of hair,
• Highest risk is in the neonatal period dimple, hemangioma, lipoma)
• Lower extremity weakness, spasticity, or
Causes numbness
• Infection, especially involving head and neck • Scoliosis
(sinusitis, mastoiditis, meningitis) • Low back pain
• Dehydration
• Perinatal events Diagnosis
• Prothrombotic disorders • Lumbosacral MRI
• Head trauma
• Malignancy Treatment
• Cardiac disease • Transection of filum terminale
• Chronic systemic disease
Prognosis
Clinical presentation • Neurologic deficits are often irreversible
• Diffuse neurologic deficits but can also have
focal deficits
pina Bifida Occulta
S
• Seizures
• Headache • Mildest form of spina bifida
• Lethargy • Spinal film will show incomplete closure of
• Nausea/vomiting some vertebrae
• Signs of increased ICP • May see midline sacral tuft of hair or dimple
on exam
Diagnosis
• No neurological symptoms
• Need venous imaging
• Often no need for intervention
• Imaging goal should be to assess blood flow
and filling defects within the venous system
• MRI/magnetic resonance venography is often Meningocele
the modality of choice in children because of
lack of radiation exposure • Protrusion of meninges from the back
• Does not contain nervous tissue
Treatment
• Typically will not have neurological
• Anticoagulation
symptoms
• Treat underlying etiology
• Treatment is surgical closure of the back
SPINAL CORD DISEASES Myelomeningocele
Tethered Cord • More severe form of spina bifida

• Broad-based defect in back with protruding
• Occurs when the distal part of the spinal cord sac containing meninges and spinal cord
is thickened and is anchored in the spinal canal
• Neurological deficits are based on level of S pinal Epidural Abscess

spinal cord involved
• Significant number of patients will develop • Causes: Bacteremia, direct extension from
hydrocephalus over time (more common local infection
when the lesion is in the thoracolumbar • Clinical presentation typically like transverse
area) myelitis
• Treatment involves closure of the back as • Most common organism: Staphylococcus
well as supportive care, including placement aureus
of VP shunt if hydrocephalus develops • MRI with contrast is the study of choice
• Lumbar puncture is usually contraindicated
• If no neurologic deficits, can consider treat-
Transverse Myelitis ment with antibiotics only
• Surgical intervention and appropriate antibi-
Definition otic therapy mainstay of treatment
• Inflammation of the spinal cord, typically
involving ≤ 3 vertebral segments Includes
both motor and sensory abnormalities Spinal Cord Trauma
Causes • Causes: Birth injury; falls; motor vehicle
• Postinfectious or postvaccination accident; sport injury, including diving/tram-
• Viral myelitis poline; gunshot/stab wounds; infection
• Autoimmune vasculitis (abscess)
• Spinal cord trauma • Complete spinal cord injury
–– Spinal shock: Complete loss of spinal cord
Clinical features function
• Acute/subacute onset –– Truncal + extremity muscles below level of
• Thoracic cord most often involved lesion flaccid, deep tendon reflexes are
• Weakness and often flaccid paralysis and are- depressed or absent, Babinski reflex absent,
flexia initially, followed by spasticity and anesthesia to all modalities, autonomic
hyperreflexia dysfunction (hypotension + bradycardia)
• Paresthesias common in the legs –– If injury more permanent ➔ Hyperreflexia,
• Sensory level muscle spasticity, permanent motor and
• Bowel and bladder dysfunction sensory deficits, and autonomic dysfunc-
• Back pain around the involved spinal tion can persist for months
segments –– Recovery rare and prognosis poor
Diagnosis
• Spinal MRI (assess the extent of lesion) Atlantoaxial Instability
• If lumbar puncture performed, CSF typically
shows lymphocytic pleocytosis; protein may • Excessive movement between C1 (atlas) and
be elevated or normal; glucose is typically C2 (axis)
normal • Ligaments mainly provide stability to the
upper cervical spine
Treatment
• Causes: Down syndrome, osteogenesis imper-
• Corticosteroids
fecta, neurofibromatosis, skeletal dysplasias,
• Supportive therapy
mucopolysaccharidoses, trauma, tumors
16 Neurology 571
• Neurologic symptoms occur when there is Congenital

impingement to the spinal cord • Familial, not transferred via mother
• Plain radiography is the main diagnostic tool, • No antibodies, multiple subtypes
preferably in an awake patient sitting or • Can be presynaptic (packaging, release) or
standing postsynaptic (slow-channel syndrome, etc.)
• CT and MRI usually reserved for a more
detailed evaluation of congenital anomalies Juvenile
or neurological impairment • Females > males
• Posterior C1–C2 fusion if there are neurolog- • Onset > 10 years
ical impairments • Clinical symptoms include generalized weak-
ness, fatigability of muscles, ptosis, and
ophthalmoplegia
DISORDERS • Diagnosis can be made by edrophonium test,
OF NEUROMUSCULAR ice pack test, EMG (electromyography), nor-
mal nerve conduction study (NCS), and anti-
JUNCTION (TABLE 16.7) bodies in serum
• Treatment can involve prednisone, anti-
Myasthenia Gravis acetylcholinesterase (AChE) drugs, thy-
mectomy in severe cases, IVIG, and
Neonatal
immunosuppression
• Maternal anti-acetylcholine receptor (AChR)
antibody transferred transplacentally
• Ptosis, feeble cry, poor suck during the first Botulism
few days
• Usually resolves within 3–5 weeks • Toxin from Clostridium botulinum
(anaerobe)
Table 16.7 Difference between upper and lower motor • Two most common sources of ingestion of
neuron lesions
spores are from honey and soil
Upper motor neuron lesions Lower motor neuron lesions • Gradual onset of hypotonia, constipation,
(UMNL) (LMNL)
poor suck and swallow, feeble cry, sluggish
Interruption of neural Interruption of neural
pathways in the brain and pathways outside the brain pupils
spinal cord before anterior and spinal cord
horn cells Diagnosis
Weakness in all muscle Weakness more distal • Isolation of toxin from stool. EMG shows
group fibrillation potentials and decremental
(Less muscle wasting) (More muscle wasting)
Spasticity Hypotonia (flaccid)
response on repetitive nerve stimulation
Reflexes are increased Reflexes are reduced
Babinski reflex; extensor Fasciculations Treatment
plantar response • Botulism immune globulin (BIG), supportive
Upgoing toe (Normal in care. Many patients go on to respiratory
< 3 years) paralysis and intubation
Study of choice: Study of choice:
CT scan (brain) Nerve conduction studies
MRI (brain/spine) Electromyogram
Creatine kinase
CT computed tomography, MRI magnetic resonance
imaging
PRIMARY MUSCULAR Diagnosis

• CPK elevated, muscle biopsy is diagnostic.
DISEASES (MYOPATHIES) Genetic testing for dystrophin gene. Echo,
EKG, and CXR to evaluate cardiac function
Duchenne Muscular Dystrophy
Treatment
Genetics
• Supportive care, physical therapy
• X-linked recessive disorder (affects only
males) resulting in an absence of dystrophin.
30% of cases are spontaneous mutations. C ongenital Myotonic Dystrophy
Incidence is 1 in 3500 male births
Genetics
Symptoms/exam • Autosomal dominant. CTG trinucleotide
• Normal newborn, develops waddling, poor repeat expansion of chromosome 19.
head control, difficulty standing or climbing Inheritance is generally from mother, and
(Gowers’ sign), hypertrophic calves (pseudo- symptoms become more severe with each
hypertrophy), generally unable to walk after successive generation (genetic anticipation)
12 years of age, death in 75% by age of 20—
dilated cardiomyopathy Symptoms/exam
• Hypotonia in the newborn, “floppy infant,”
Diagnosis hollowing of temporal bones, tenting of upper
• Creatine phosphokinase (CPK) elevated even lip, feeding issues, respiratory distress due to
prior to muscle weakness. Muscle biopsy is intercostal and diaphragmatic weakness,
diagnostic. Genetic testing for dystrophin arthrogryposis; some patients have cataracts
gene. EMG shows characteristic myopathic
features. Echo, EKG, and CXR to evaluate Diagnosis
cardiac function • DNA testing for CTG repeats, CPK not
useful
Treatment
• Supportive care and physical therapy. Treatment
Corticosteroids are sometimes recommended • Supportive care, physical therapy
to delay wheelchair use
Becker Muscular Dystrophy NEUROPATHIES
Genetics Acute Inflammatory Demyelinating

• Defect is at same locus as Duchenne muscu- Polyneuropathy (Guillain–Barré
lar dystrophy, but patients have later onset Syndrome, GBS)
and milder course
• Postinfectious polyneuropathy that results in
Symptoms/exam paresthesias and ascending symmetric periph-
• Symptoms onset later than Duchenne patients, eral neuropathy. Early calf pain is also com-
but also present with pseudohypertrophy of mon. Occurs in healthy individuals, days to
calves and wasting of thigh muscles. Patients weeks after an antecedent illness
ambulatory until late adolescence and early • Miller Fisher variant presents with facial
adulthood. Becker patients can also present weakness, ophthalmoplegia, ataxia, and
with cardiomyopathy areflexia
16 Neurology 573
Causes Course and prognosis

• Strongest association with bacteria • Prognosis for childhood GBS generally is
Campylobacter jejuni, also associated with excellent
Mycoplasma pneumoniae • Full recovery within 6–12 months, with the
• Autoimmune conditions, surgery, and majority of those who do not fully recover
vaccinations having only mild disabilities
• Weakness ereditary Motor Sensory
H
–– Refusal to walk, walking on a wide base, or Neuropathy (HMSN) (Charcot–
difficulty with running or climbing stairs Marie–Tooth Disease)
–– Usually begins distally in the legs and
ascends • Most common inherited peripheral neuropa-
• Symmetric diminished or absent reflexes thy. Group of disorders characterized by
early in the course defective peripheral nerve myelination. Deep
• Cranial nerve abnormalities are frequent; tendon reflexes are markedly diminished or
facial nerve is the most commonly affected absent; vibration sense and proprioception
cranial nerve, and the weakness is often are significantly decreased. Pain and temper-
bilateral ature sense intact
• Paresthesias • HMSN I: Charcot–Marie–Tooth type 1
• Autonomic instability: Arrhythmia, ortho- –– Autosomal dominant: Demyelinating con-
static hypotension, hypertension, bladder dition. Asymptomatic until late childhood
dysfunction or adolescence. Palpable enlargement of
• Acute illness usually peaks in severity nerves
2 weeks after onset; recovery may take weeks • HMSN II: Charcot–Marie–Tooth type 2
to months –– Autosomal dominant or recessive: Axonal
condition. Onset in childhood and associ-
Diagnosis ated with severe wasting of calf muscles
• Primarily on basis of clinical appearance. with pes cavus and wasting of dorsal inter-
CSF shows elevated protein without an ele- ossei of hands, foot drop; ankle–foot ortho-
vated cell count (albuminocytologic dissocia- sis to help with the foot drop
tion); EMG can take weeks to show positive • HMSN III: Dejerine–Sottas disease
findings, and first abnormality is the F wave; –– Autosomal dominant or recessive: Onset
nerve conduction studies are slow with evi- early in infancy; delayed milestones.
dence of conduction block Peripheral nerves thicken due to myelin
loss, followed by remyelination in layers.
Treatment Cross section looks like onion bulb
• IVIG and plasmapheresis—treatment should • HMSN IV: Refsum disease
begin as soon as clinical diagnosis is –– Autosomal recessive: Peroxisomal disor-
determined der. Problem of phytanic acid storage.
• Supportive care and hospitalization until Retinitis pigmentosa, hearing loss
patient is stabilized and ICU care if there are
symptoms of bulbar palsy, vital capacity is Diagnosis
compromised, and/or autonomic instability • Genetic testing, EMG/NCS
Spinal Muscular Atrophy (SMA) Table 16.8 Difference between upper and lower motor
neuron lesion in facial nerve palsy
• Autosomal recessive condition affecting the Upper motor neuron facial Lower motor neuron facial
anterior horn cell. Characterized by three dif- nerve palsy nerve palsy
Causes: Stroke Causes: Idiopathic, viral
ferent types ranging in severity: SMA type 1
infection
(Werdnig–Hoffmann), SMA type 2 (no The angle of the mouth falls The angle of the mouth
eponym), and SMA type 3 (Kugelberg– falls
Welander) Eye closure and blinking are Weak or absent eye closure
not affected and blinking
• Severe hypotonia; SMA type 1 presents prior
to 6 months of age amsay Hunt Syndrome
R
• Frog-leg position
• Difficulty feeding • Infectious neuropathy caused by herpes zos-
• Tongue fasciculations, atrophy with progres- ter oticus infection in the geniculate ganglion
sion of disease leading to peripheral CN VII paresis and/or
• No sphincter loss, sensory loss, or cognitive other cranial nerve involvement
loss
Diagnosis • Peripheral facial nerve paresis
• Gene mutation screening • Deafness
• Vertigo
Management • Nausea
• Respiratory, nutritional, orthopedic support • Pain
• Gene therapy [1]
Diagnostic criteria
• Herpes zoster oticus lesions present in the ear
Familial Dysautonomia (Riley–Day and on the face
Syndrome) • Peripheral facial nerve paresis with taste dis-
turbance and reduction of tear secretion
• Inherited neuropathy affecting sensory and • Sensitivity disturbances in the innervation
autonomic nerves area of CN V
• Symptoms • Sensitivity disturbance in the cervical derma-
–– Insensitivity to pain, temperature dysregu- tomes (usually C2–C4)
lation, difficulty feeding, blood pressure • Lesion of CN VIII (impaired hearing)
instability, vomiting, sweating spells
Treatment
• Acyclovir
Bell’s Palsy (Table 16.8) • Corticosteroid
• Gabapentin (pain control)
• Idiopathic facial nerve (CN VII) paralysis. • Earlier treatment (within 3 days) associated
Can occur after viral upper respiratory infec- with improved outcomes
tion. Usually unilateral and self-limiting
16 Neurology 575
Tick Paralysis • Genetic and/or degenerative (i.e., ataxia tel-

angiectasia, Friedreich ataxia, spinocerebel-
• Uncommon, noninfectious, neurologic syn- lar ataxia)
drome characterized by acute ataxia progress-
ing to ascending paralysis
• Caused by salivary neurotoxins of several A cute Cerebellar Ataxia
species of ticks
• Neurotoxin causes impaired neurotransmitter • Relatively common in children, often in the
release at synaptic terminals second decade of life
• Most commonly associated with viral illness
Clinical presentation (varicella, Epstein–Barr virus)
• Fatigue and weakness: Starts in legs and pro- • Thought to be due to molecular mimicry
gresses rapidly within 2–7 days
• Irritability Clinical features
• Muscle pain • Rapid onset of ataxia, over hours to days
• Paresthesias • Typically manifests as a gait disturbance
• Can also see ataxia (e.g., when reaching for
Evaluation objects) or dysarthria
• Serum studies and neuroimaging are usually • Mild CSF pleocytosis
normal • MRI may show enhancement
Treatment Prognosis
• Removal of tick (usually found on scalp) • Usually self-limiting
leads to rapid improvement • May take several weeks or months for com-
• Provide respiratory support if required plete resolution of symptoms
• Increased risk of mortality with missed diag-
nosis due to respiratory failure
Ataxia Telangiectasia
DISORDERS OF MOVEMENT • Autosomal recessive

• Frequency of approximately 1 per 40,000
Ataxia births
• Causative gene—ataxia telangiectasia
• Definition: “…disturbance in the smooth per- mutated (ATM) gene located on chromo-
formance of voluntary motor acts” [2] some 11
Differential diagnosis (broad spectrum) Clinical features (Fig. 16.4)

• Infectious or postinfectious • Symptom onset by 2–3 years old
• Posterior fossa tumors • Impairment in coordinated muscle move-
• Neuroblastoma (opsoclonus myoclonus ments involving gait, trunk, and limbs
syndrome) • Progressive symptoms lead to loss of ambula-
• Acute hemorrhage tion in childhood
• Toxic (i.e., alcohol, benzodiazepines) • Movement disorder precedes the oculocuta-
• Congenital (i.e., progressive hydrocepha- neous telangiectasias
lus, Chiari malformation, Dandy–Walker • Jerking eye movements and oculomotor
syndrome) apraxia are common
Table 16.9 Difference between ataxia telangiectasia and

Friedreich ataxia
Ataxia telangiectasia Friedreich ataxia
Autosomal recessive Autosomal recessive,
trinucleotide repeat
Telangiectasias 3-6 y
1 per 40,000–100,000 1–2 per 100,000
Age of onset: 2–3 years Age of onset: Early adolescence
Elevated levels of Normal levels of serum
serum alpha-fetoprotein alpha-fetoprotein
Decreased serum Normal immunoglobulins
immunoglobulins (IgA,
High incidence of carcinoma and lymphoma (early adulthood) IgG, and IgE)
Oculocutaneous No oculocutaneous
telangiectasias telangiectasias
Ataxia, ocular apraxia, Ataxia, nystagmus, diabetes
pulmonary infections mellitus, kyphoscoliosis,
weakness, loss of deep tendon
reflexes
High incidence of carcinoma and lymphoma (early adulthood) Negative Romberg sign, Positive Romberg sign, poor
intact sensation sensation
Fig. 16.4 Sequence of major symptoms in ataxia No cardiomyopathy Cardiomyopathy
telangiectasia Normal arch foot High arched foot
• Immunologic deficiencies—increase in sino- Clinical features

pulmonary infections • Onset of symptoms typically during early
• Cerebellar degeneration adolescence
• Increased sensitivity to radiation • Progressive trunk and limb ataxia
• Increased risk of lymphoreticular neoplasms • Muscle weakness
(leukemia, lymphoma) • Dysarthria
• Loss of deep tendon reflexes
Diagnosis
• Upgoing plantar responses
• Elevated levels of serum alpha-fetoprotein
• Sensory neuropathy (loss of vibration sense
• Decreased serum immunoglobulins (IgA,
and proprioception)
IgG, and IgE)
• Scoliosis is common
Prognosis • Cardiomyopathy
• Often wheelchair-bound by 10 years of age • Diabetes mellitus (seen in up to 30% of
• Median survival is about 25 years patients)
Diagnosis and management

riedreich Ataxia (Table 16.9)
F • Specific genetic testing
• Typically wheelchair-bound within 10 years
• Autosomal recessive of symptom onset
• 98% of patients are homozygous for a GAA • Supportive care with symptomatic treatment
trinucleotide repeat expansion in intron 1 of (i.e., cardiomyopathy, diabetes mellitus,
frataxin gene (FXN) scoliosis)
16 Neurology 577
Tics • Tics can be exacerbated by environmental

stimuli, stress, and poor sleep
Definition • Tics typically do not occur in sleep
• Intermittent, sudden, discrete, repetitive, non- • Comorbid behavioral symptoms: Attention
rhythmic movements or vocalizations. Tics deficit hyperactivity disorder (ADHD), obses-
typically occur multiple times per day. With sive compulsive disorder (OCD), anxiety dis-
typical tics, the anatomic location can change orders, mood disorders, sleep disorders,
over time, as can their frequency, type, and conduct, and oppositional behavior
severity
Cause
Types • Exact pathophysiology not completely
• Motor: Involves skeletal muscle (simple or understood
complex) • Likely involves the basal ganglia
• Vocal: Involves the diaphragm or laryngeal– • Most common is transient tic disorder (tics
pharyngeal muscles (simple or complex) for at least 4 weeks that resolve before 1 year)
• Simple motor tic: Involves a single muscle or • For primary tic disorder—diagnosis is based
localized group (eye blinks, facial grimacing, on history plus normal neurologic exam aside
shoulder or head jerks) from tics
• Simple vocal tic: Throat clearing, sniffing,
coughing, or grunting Treatment
• Complex motor tic (often prolonged and can • Reassurance
appear purposeful): Head shaking, trunk flex- • Anticipatory guidance and education
ion, finger tapping, jumping • Often no medications needed
• Complex vocal tic: Involves uttering words or • If sufficient morbidity—typical first-line
phrases; coprolalia (uttering swear words) or agents are alpha-2-agonists (clonidine or
echolalia (repeating the words or phrases of guanfacine)
others) • Behavioral therapies
• Treatment of comorbidities such as ADHD,
Epidemiology OCD, anxiety, or mood disorders
• Approximately 20% prevalence in the
population
• Tends to be familial; males > females Tourette Syndrome
• Typically appears in first decade of life with
median age of onset being 6–7 years Diagnostic indications
• There is usually significant improvement by • Presence of both motor and vocal tics
late teens or early adulthood • Duration of tics > 12 months
• Most common presenting tic is eye blinking • No tic-free interval > 3 month’s duration
• Age of onset < 21 years
Clinical features • Tourette syndrome is one entity in a spectrum
• Tics are often preceded by an urge or sensa- of disorders
tion, sometimes manifested as nonspecific • Coprolalia occurs in possibly < 10% of
anxiety patients.
• Performing the tic relieves the urge or • Male to female ratio of 3:1
anxiety • Associated behavioral problems: ADHD,
• Tics can often be suppressed for short periods OCD, anxiety, depression, episodic outburst
of time (rage), learning disabilities, sleep disorders
Treatment—symptomatic • Types include: Oculogyric crisis, torticollis,

• Nonpharmacologic—variety of behavioral opisthotonus, macroglossia
treatments
• Pharmacologic: Causes
–– Milder tics—alpha-adrenergics (clonidine, • Medication adverse effect (gastrointestinal
guanfacine) medications, antipsychotics, antiepileptics,
–– More severe tics—typical and atypical sedatives)
neuroleptics • Can be caused by the medications that treat
• Surgical—Deep brain stimulation dystonia (see below)
• Head trauma
Sydenham Chorea Treatment

• Anticholinergic agent, benzodiazepine,
Definition of chorea antihistamine
• Frequent, brief, purposeless movement that
are chaotic and unpredictable and that flow
from one body part to another DEVELOPMENTAL DISORDERS
• Sydenham chorea is one of the major Jones
criteria for diagnosis of acute rheumatic fever C erebral Palsy (Table 16.10)
(ARF)
• Seen in 10–40% of children with ARF Definition
• Most common between ages 5 and 15 years • A group of disorders that involve the develop-
• Typically, the chorea begins several weeks to ment of movement and posture leading to
months after a group A beta-hemolytic strep- limitations in activity, attributable to nonpro-
tococcal infection
• Gradual progression with behavioral changes Table 16.10 Etiology and risk factors for cerebral palsy
(impulsivity, aggression, OCD behaviors) Perinatal brain injury Toxins
along with emotional lability Hypoxia, ischemia In utero alcohol
exposure
Diagnosis Asphyxia Methyl mercury
Neonatal stroke (ischemic perinatal Congenital
• Clinical history and laboratory data; 25% of
infarction, sinovenous thrombosis) infections
patients serologically negative (TORCH)
Prematurity Postnatal
Treatment Periventricular leukomalacia Neonatal
• Studies have failed to confirm benefits of meningitis
treatment with IVIG, corticosteroids, or Intraventricular hemorrhage Bilirubin toxicity
(kernicterus)
plasma exchange for the presumed autoim-
Developmental abnormalities Other
mune process Congenital brain malformations Male gender
Genetic disorders; metabolic Multiple gestation
disorders
Dystonic Reactions Prenatal
Maternal chorioamnionitis
Intrauterine growth restriction
Definition of dystonia
Prothrombotic abnormalities
• Involuntary, sustained, and often painful Infertility
muscle contractions Adapted from Swaiman et al. [1], with permission
• Caused by an imbalance between cholinergic
and dopaminergic stimulation
16 Neurology 579
gressive disturbances that occurred in the • Orthopedic management of contractures,

developing fetus or infant brain including surgery
• Incidence of cerebral palsy is approximately • Use of orthotics
2.5 per 1000 births • Therapies to improve functional gains and
• Key aspects: slow the progression of contractures (physi-
–– Disorder of motor function cal and occupational therapy)
–– Clinical manifestations may change over • Learning and cognitive evaluations (speech
time, but the causative lesion is static therapy, individualized educational plan
–– The lesion occurs in the brain at some point [IEP] in school, special education)
during the brain’s developmental period • Growth and nutrition, including monitoring
of swallowing and gastroesophageal reflux
General manifestations of cerebral palsy • Respiratory monitoring for obstructive sleep
• Delayed motor milestones apnea, risk of chronic aspiration, develop-
• Abnormal muscle tone ment of restrictive lung disease secondary to
• Hyperreflexia scoliosis
• Hand preference before 1 year of age: A red • Management of sleep problems
flag for possible hemiplegia • Dental care—increased risk of malocclusion,
• Growth disturbances: Especially failure to dental caries, and gingivitis
thrive
• Persistence of developmental reflexes Types of cerebral palsy
• Presence of pathological reflexes • Spastic
• Failure to develop maturational reflexes such –– Hemiplegia
as the parachute response –– Diplegia
• Clinical manifestations may change with –– Quadriplegia
maturation • Dyskinetic
• No evidence of disease progression or devel- –– Choreoathetoid
opmental regression –– Dystonic
• Hypotonic
Diagnosis of cerebral palsy • Mixed
• History and physical examination (including
thorough neurologic exam)
• Review pregnancy and delivery records Spastic Hemiplegia
• Neuroimaging (preferably MRI)
• Ophthalmologic and auditory evaluation Causes
• Speech and language evaluation • Most common cause is perinatal stroke
• Metabolic and genetic testing should not be • More commonly involving the left hemi-
done routinely unless there is an atypical clini- sphere (affecting right side of body)
cal presentation and nonspecific neuroimaging • Represents approximately 30% of all cases of
• EEG if concern for seizures cerebral palsy
Management/complications of cerebral palsy • Early hand preference
• Family-centered care • Difficulty using the affected hand—trouble
• Multidisciplinary approach with pincer grasp
• Symptomatic treatment of seizures • Growth arrest of abnormal side—more prom-
• Symptomatic treatment of spasticity (oral inent in distal arm and leg
baclofen, baclofen pump, botulinum toxin, • Facial involvement is rare
diazepam) • Circumduction gait with toe walking
• Signs of upper motor neuron involvement on • Signs of upper motor neuron involvement—
affected side—hyperreflexia, ankle clonus, hyperreflexia in upper and lower extremities,
and extensor plantar response ankle clonus, and extensor plantar responses
• Seizures • Spasticity of hip muscles may lead to femur
subluxation
• Flexion contractures of elbows and wrists
Spastic Diplegia • Visual and hearing impairment more com-
mon in spastic quadriplegic children
Causes • Learning and intellectual disabilities also
• Most commonly seen in preterm infants more common
• Often associated with periventricular • Seizures
leukomalacia
• Bilateral leg involvement and commonly may
have some degree of arm impairment Dyskinetic Cerebral Palsy
• May have asymmetric impairment Causes
• Scissoring of legs when held in vertical • Presence of extrapyramidal signs; choreoath-
position etoid or dystonic
• Toe walking in older children • Problems with posture and involuntary
• Spasticity of hip muscles may lead to femur movements
subluxation • Usually caused by damage or malformation
• Signs of upper motor neuron involvement in of basal ganglia or cerebellum
the legs—hyperreflexia, ankle clonus, and • Often associated with hypoxic–ischemic
extensor plantar responses brain injury or kernicterus
Spastic Quadriplegia • Choreoathetoid
–– Large-amplitude, involuntary movements
Causes –– Athetosis usually involves the distal limbs
• White matter damage (periventricular –– Chorea may involve the face, limbs, and
leukomalacia) possibly the trunk
• Abnormal brain development –– Difficulty with speech
• Intracranial hemorrhage –– Upper motor neuron involvement
• Hypoxic–ischemic encephalopathy or –– Seizure and intellectual disability can also
asphyxia be present
• Kernicterus • Dystonic
• Perinatal CNS infections –– Trunk muscles and proximal limbs more
involved
Clinical presentation –– Uncommon form of cerebral palsy
• Generalized increase in muscle tone
• Legs involved more than the arms
• Decreased limb movements Rett Syndrome
• Difficulties in swallowing—predisposing to
aspiration pneumonia • X-linked
• Spasticity • Mutation in MECP2 gene
16 Neurology 581
• Affects approximately 1 in 10,000 live female Table 16.11 Primitive reflexes
births Age at
• Males with the mutation typically die before Reflex Response disappearance
or soon after birth. Sucking Sucking response when 3–4 months
something touches the
roof of the mouth
Clinical Features
Rooting Turning the head toward 3–4 months
• Neurologic regression starting between 1.5 the cheek being stroked
and 3 years of age with loss of acquired hand Stepping Stepping movements 6–8 weeks
skills and spoken language when soles of feet touch
• Can also have autistic features with social a flat surface
Palmar grasp Finger flexion 6 months
withdrawal, decreased eye contact, and Plantar grasp Toe flexion 15 months
decreased response to visual and auditory Asymmetric Extension of extremities3–4 months
stimuli tonic neck on side of head turn and
• Extreme irritability and anxiety (fencer flexion of extremities on
• After regression, there is stabilization of skills posture) the opposite side
Moro Abduction of upper 4–6 months
• Severe intellectual disability (although with extremities followed by
the severe communication impairment, accu- flexion
rate assessment is difficult) Parachute Extension of arms as Appears ≈
• Movement abnormalities—repetitive hand infant is projected 8–9 months;
stereotypies, gait (ataxia and apraxia), dysto- toward the floor permanent
nia, axial hypotonia (initially), increased tone
with rigidity (later) rimitive Reflexes (Table 16.11)
P
• Seizures are common
• Acquired microcephaly
• Gastrointestinal abnormalities (GERD,
constipation) PEARLS AND PITFALLS
• Scoliosis
• Sleep disorders • Complex febrile seizures are focal and pro-
• Bruxism longed (> 15 min) or occur multiple times in
24 h.
Diagnostics • 1 Hz spike-wave discharges are seen in
• Specific genetic testing Lennox–Gastaut syndrome, 3 Hz spike-wave
• Abnormal EEG discharges are seen in childhood absence epi-
• MRI initially normal but will later show gen- lepsy, and 4 Hz spike-wave discharges are
eralized atrophy of the cerebral hemispheres seen in juvenile myoclonic epilepsy.
• Guillain–Barré syndrome should be recog-
Treatment
nized as a neurologic emergency, because
• No curative treatment available
patients are at risk for respiratory failure dur-
• Symptomatic treatments only (i.e., anticon-
ing the course of illness.
vulsants for seizures, reflux medications for
GERD)
• Gene therapy is now available for patients • Tics can be suppressed for a period of time
with spinal muscular atrophy that has led to and do not occur during sleep.
improvement in motor milestones [1]. • For a diagnosis of Tourette syndrome, patients
• Consider possible underlying immunodefi- must have had both motor and vocal tics, and
ciency with a new diagnosis of Ramsay–Hunt the tics have to be present for > 1 year.
syndrome. • Early hand preference (< 1 year) is a red flag
• Patients with NF1 are at risk for hypertension for possible hemiplegia and cerebral palsy.
secondary to renal artery stenosis and • Kernicterus (damage to the brain from sig-
pheochromocytoma. nificantly elevated bilirubin) is associated
• NF1 patients should be monitored for preco- with dyskinetic cerebral palsy.
cious puberty, because optic pathway gliomas
can extend into the hypothalamus. Acknowledgments The authors gratefully
• Vigabatrin is the treatment of choice for acknowledge the contributions of Rujuta Bhatt
infantile spasms secondary to tuberous Wilson, MD, Semel Institute for Neuroscience and
sclerosis. Human Behavior, UCLA, Los Angeles, California,
• Tuberous sclerosis patients should be mon- to the first edition of this chapter, many of which
itored for symptoms of increased intracra- have been incorporated into this edition as well.
nial pressure, because subependymal giant
cell astrocytomas can lead to obstructive
hydrocephalus. References
• Sturge–Weber syndrome can be a cause of
epilepsia partialis continua or simple motor 1. Finkel RS, Mercuri E, Darras BT, Connolly
status epilepticus. AM, Kuntz NL, Kirschner J, ENDEAR Study
• Patients with lissencephaly can present with Group, et al. Nusinersin versus sham control in
seizures in the neonatal period but can also infantile-onset spinal muscular atrophy. N Engl
present with infantile spasms later during J Med. 2017;377(18):1723–32.
infancy. 2. Swaiman KF, Ashwal S, Ferriero DM, Schor
• Be sure to account for parents’ head circum- NF, Finkel RS, Gropman AL, et al. Swaiman’s
ference because familial macrocephaly is one pediatric neurology: principles and practice. 6th
of the most common causes of macrocephaly. ed. Edinburgh: Elsevier; 2018.
• Microcephaly in a female 6–18 months of age
should lead to evaluation of Rett syndrome.
• Acquired microcephaly associated with Rett Suggested Reading
syndrome is when an infant initially has a
normal head circumference at birth, but the Abend N, Loddenkemper T. Management of
head circumference does not grow appropri- pediatric status epilepticus. Curr Treat Options
ately on a typical growth curve. Neurol. 2014;16(7):1–16.
• The presence of Cushing’s triad (hyperten- Armangue T, Petit-Pedrol M, Dalmau
sion, bradycardia, irregular respiration) J. Autoimmune encephalitis in children. J Child
should prompt urgent management of Neurol. 2012;27(11):1460–9.
increased intracranial pressure. Beslow LA, Jordan LC. Pediatric stroke: the
• Overdrainage of VP shunts can also be a importance of cerebral arteriopathy and vas-
cause of headaches that worsen upon sitting cular malformations. Childs Nerv Syst.
or standing. 2010;26(10):1263–73.
16 Neurology 583
Chadehumbe MA, Greydanus DE, Feucht C, Patel Jacobs H, Gladstein J. Pediatric headache: a clini-
DR. Psychopharmacology of tic disorders in cal review. Headache. 2012;52(2):333–9.
children and adolescents. Pediatr Clin N Am. Katz DM, Berger-Sweeney JE, Eubanks JH, Justice
2011;58(1):259–72. MJ, Neul JL, Pozzo-Miller L, et al. Preclinical
Choe MC, Blume HK. Pediatric posttrau- research in Rett syndrome: setting the founda-
matic headache: a review. J Child Neurol. tion for translational success. Dis Models Mech.
2015;31(1):76–85. 2012;5(6):733–45.
Delatycki MB, Corben LA. Clinical fea- Knoch J, Kamenisch Y, Kubisch C, Berneburg
ture of Friedreich ataxia. J Child Neurol. M. Rare hereditary diseases with defects in DNA-
2012;27(9):1133–7. repair. Eur J Dermatol. 2012;22(4):443–55.
Dodge NN. Cerebral palsy: medical aspects. Lerner JT, Matsumoto JH, Wu JY. Infantile spasms.
Pediatr Clin N Am. 2008;55(5):1189–207. In: Sirven J, Stern J, editors. Atlas of video-EEG
Finkel RS, Mercuri E, Darras BT, Connolly AM, monitoring. New York: McGraw Hill; 2010.
Kuntz NL, Kirschner J, ENDEAR Study Group, p. 329–40.
et al. Nusinersin versus sham control in infan- Matsumoto JH, Lerner JT. First steps to epilepsy
tile-onset spinal muscular atrophy. N Engl J syndrome diagnosis. In: Auvin S, Sankar R, edi-
Med. 2017;377(18):1723–32. tors. Acute seizures in children in the emergency
Forsyth R, Newton R. Paediatric neurology, setting. Montrouge: John Libbey Eurotext;
Oxford specialist handbooks in paediatrics. 3rd 2013. p. 175–85.
ed. Oxford: Oxford University Press; 2018. Menkes JH, Sarnat HB, Maria BL, editors. Child
Ghanem I, El Hage S, Rachkidi R, Kharrat K, neurology. 7th ed. Philadelphia: Lippincott
Dagher F, Kreichati G. Pediatric cervical spine Williams & Wilkins; 2005.
instability. J Child Orthop. 2008;2(2):71–84. Nussinovitch M, Prais D, Volovitz B, Shapiro R,
Gothe R, Kunze K, Hoogstraal H. The mecha- Amir J. Post-infectious acute cerebellar ataxia
nisms of pathogenicity in the tick paralyses. J in children. Clin Pediatr. 2003;42(7):581–4.
Medical Entomol. 1979;16(5):357–69. Review. Pearl PL. Epilepsy syndromes in childhood.
Guerrini R, Pellacani S. Benign childhood focal Continuum (Minneap Minn). 2018;24(1, Child
epilepsies. Epilepsia. 2012;53(Suppl 4):9–18. Neurology):186–209.
Hirtz D, Ashwal S, Berg A, Bettis D, Camfield C, Roser T, Bonfert M, Ebinger F, Blankenburg
Camfield P, et al. Practice parameter: evaluat- M, Ertl-Wagner B. Primary versus secondary
ing a first nonfebrile seizure in children: report headache in children: a frequent diagnostic
of the quality standards subcommittee of the challenge in clinical routine. Neuropediatrics.
American Academy of Neurology, The Child 2013;44(1):34–9.
Neurology Society, and The American Epilepsy Sarnat HB. Disorders of segmentation of the neural
Society. Neurology. 2000;55(5):616–23. tube: Chiari malformations. Handb Clin Neurol.
Hirtz D, Berg A, Bettis D, Camfield C, Camfield 2008;87:89–103.
P, Crumrine P, Quality Standards Subcommittee Schlaggar BL, Mink JW. Movement disorders in
of the American Academy of Neurology, children. Pediatr Rev. 2003;24(2):39–51.
Practice Committee of the Child Neurology Sheehan JP, Jane JA, Ray DK, Goodkin
Society, et al. Practice parameter: treatment of HP. Brain abscess in children. Neurosurg
the child with a first unprovoked seizure: report Focus. 2008;24(6):E6. https://doi.org/10.3171/
of the quality standards subcommittee of the FOC/2008/24/6/E6. Review.
American Academy of Neurology and the prac- Singer HS, Mink JW, Gilbert DL, Jankovic J, edi-
tice committee of the Child Neurology Society. tors. Movement disorders in childhood. 2nd ed.
Neurology. 2003;60(2):166–75. London: Elsevier; 2016.
Solmaz I, Izci Y, Albayrak B, Cetinalp E, Kural C, Wagner G, Klinge H, Sachse M. Ramsay Hunt syn-
Sengul G, et al. Tethered cord syndrome in child- drome. J Dtsch Dermatol Ges. 2012;10(4):238–
hood: special emphasis on the surgical technique 44. [Article in English and German].
and review of the literature with our experience. Waterhouse E. Status epilepticus. Continuum
Turk Neurosurg. 2011;21(4):516–21. (Minneap Minn). 2010;16(3 Epilepsy):199–227.
Subcommittee on Febrile Seizures. Clinical Williams VC, Lucas J, Babcock MA, Gutmann
practice guidelines – febrile seizures: guide- DH, Korf B, Maria BL. Neurofibromatosis type
line for the neurodiagnostic evaluation of the 1 revisited. Pediatrics. 2009;123(1):124–33.
child with a simple febrile seizure. Pediatrics. Wirrell E, Nickels KC. Pediatric epilepsy syn-
2011;127(2):389–94. dromes. Continuum (Minneap Minn). 2010;16(3
Swaiman KF, Ashwal S, Ferriero DM, Schor Epilepsy):57–85.
NF, Finkel RS, Gropman AL, et al., editors. Zamora C, Castillo M. Neuroradiology companion:
Swaiman’s pediatric neurology: principles and methods, guidelines, and imaging fundamentals.
practice. 6th ed. Edinburgh: Elsevier; 2018. 5th ed. Philadelphia: Wolters Kluwer; 2017.
Ophthalmology
17
Kyle E. Miller and Shira L. Robbins
VISION SCREENING [1] Painful Erythematous Eye
• Screening of vision at routine intervals can Presentation

prevent lifelong blindness • Unilateral or bilateral red eye with pain and/
• All ages: Ocular history, external inspection, or photophobia
red reflex testing, pupil examination • Discharge presence and type can give insight
• Six months and older: Add ocular motility into diagnosis
assessment
• Instrument-based screening, if available, Clinical evaluation
should be started by 12 months of age • Unilateral vs. bilateral
• Visual acuity should be tested with age- • Discharge? Watery vs. mucoid. Amount?
appropriate optotypes in cooperative 3-year- Frequency?
olds and older • Pain vs. itch. An itchy eye is frequently a sign
• Preferred optotypes for younger children of allergy or infection
include LEA® or HOTV symbols with • History of trauma or foreign object/chemical
advancement to letter optotypes for those exposure
who can distinguish letters • Visual acuity
• Fixation and following visual behavior
descriptors are used in those under 3
Ophthalmia Neonatorum
Performing visual acuity screening
• Ensure eye chart is in a well-lit area with min- • Conjunctivitis occurring in the 1st month of
imal distractions life
• Ensure child is not peeking through fingers.
Consider using a patch
phthalmia Neonatorum due to N.
O
• Test each eye individually; a child who is
blind in one eye can be missed if both eyes gonorrhoeae
are tested simultaneously
K. E. Miller
• Hyperacute conjunctivitis with hyper-puru-
Department of Ophthalmology, Naval Medical Center Portsmouth, lent discharge in the first 3–5 days of life
Portsmouth, VA, USA
S. L. Robbins (*)
Department of Ophthalmology, Ratner Children’s Eye Center,
University of California San Diego, La Jolla, CA, USA
e-mail: srobbins@ucsd.edu

586 K. E. Miller and S. L. Robbins
Diagnosis Management
• Culture and Gram stain of eye discharge will • Oral erythromycin for a minimum of 14 days
reveal Gram-negative intracellular diplococci • No effective prophylaxis is currently available
Neisseria gonorrhoeae • Ensure source of infection (i.e., mother and
• Sepsis workup and evaluation for dissemi- her sexual partners) are treated as well
nated systemic infections are critical
• Infants should be tested also for HIV, chla-
mydia, and syphilis Ophthalmia Neonatorum due
to Herpes Simplex
Treatment of gonococcal conjunctivitis
• Parenteral ceftriaxone 25–50 mg/kg, not to Background
exceed 125 mg, must be given immediately • Onset usually around 2nd week of life, typi-
• Delay in treatment can cause corneal perfora- cally later than chlamydia or gonorrhea
tion and permanent vision loss • Most frequently associated with maternal
• Frequent lavage of the fornices with normal herpes simplex virus (HSV)-2 infection with
saline is recommended increased risk with active lesions in vaginal
• Topical antibiotics may be indicated if there delivery in the neonatal setting
is corneal involvement
Prophylaxis • Watery discharge
• Erythromycin topical ointment is effective • Eyelid lesions (usually vesicles), conjunctivi-
prophylaxis after birth tis, keratitis, and cataracts are all possible
• Silver nitrate is rarely used today and can
cause a chemical conjunctivitis Diagnosis
• Clinical presentation +/− viral cultures
Management
phthalmia Neonatorum due
O • Systemic workup necessary to rule out cen-
to Chlamydia tral nervous system involvement
• Systemic acyclovir for 14 days. Topical anti-
Background viral eye drops may be added in some cases
• Onset occurs around 1 week of age
• Associated with infantile pneumonitis
Acute Bacterial Conjunctivitis
• Minimal-to-moderate mucopurulent discharge Background
• Eyelid edema • Acute bacterial nongonococcal conjunctivitis
• Papillary conjunctivitis is usually benign and self-limited; however,
• Pseudomembrane formation in tarsal antibiotics can expedite the return to normal
conjunctiva activities
Diagnosis Bacterial causes
• Culture of conjunctival scrapings, direct fluo- • Staphylococcus aureus, S. epidermidis,
rescent antibody test, and enzyme immunoas- Streptococcus pneumoniae, Moraxella catarrh-
says are also available alis, and Pseudomonas are common causes
17 Ophthalmology 587
Management
• Treatment of the cause
Acute Hemorrhagic Conjunctivitis

Fig. 17.1 A 13-month-old child presents with fever, bilat- Causes
eral eye discharge, and ear infection • Coxsackievirus A24
• Enterovirus 70
• School-aged children: Streptococcus pneu-
moniae, Haemophilus, and Moraxella Clinical presentation
• Highly contagious disease
Clinical presentation • Large subconjunctival hemorrhage, can
• Mild hyperemia involve the entire subconjunctival space
• Scant purulent discharge (Fig. 17.1) • Patients also may present with fever and
• May have significant conjunctival injection headache
with moderate purulent discharge
Management
Management • Treatment is supportive, and complications
• Empiric topical antibiotic agents (e.g., are rare
sulfacetamide, trimethoprim polymyxin B,

tobramycin, erythromycin ointment, fluoro-
quinolones, azithromycin) to shorten the Pharyngoconjunctival Fever
duration and reduce the amount of contagion
of the disease [2] Background
• Fourth-generation fluoroquinolones (moxi- • Highly infectious illness affecting the eye and
floxacin, gatifloxacin, besifloxacin) have pharynx
more rapid effectiveness and simplified dos- • Adenovirus types 3, 4, 5, and 7 (the most
ing regimen but are considerably more expen- common cause)
sive and should perhaps be reserved for more • Often affects young children
severe or recalcitrant infections • May lead to community outbreak
Parinaud Oculoglandular Syndrome • Fever
• Pharyngitis
Background • Follicular conjunctivitis
• Most frequently by Bartonella henselae (cat- • Regional lymphoid hyperplasia with tender,
scratch disease) enlarged preauricular adenopathy
• Many other causes, e.g., Chlamydia trachoma- • May cause punctate lesions in the corneal
tis, Francisella tularensis, and Mycobacterium epithelium (best seen with fluorescein stain-
tuberculosis ing) that warrant an ophthalmologic
referral
• Unilateral granulomatous conjunctivitis Treatment
• Swollen ipsilateral preauricular lymph node • Supportive care
• Submandibular lymphadenopathy • The conjunctivitis is self-limited, usually
lasting no more than 10 days
Molluscum Contagiosum
Conjunctivitis
Background
• Common viral infection in children
• Lesions may be anywhere on the body, includ-
ing the eyelid
• Classic dome-shaped, umbilicated lesions
• Lesions shed viral particles into eyes, causing
irritation
• Red, irritated eye with follicular conjunctival
reaction Fig. 17.2 Fluorescein staining. (Photo courtesy of Kyle Miller,
• Molluscum lesions around lid M.D., Naval Medical Center Portsmouth, Portsmouth, VA) of
• May present as a recurrent red eye initially corneal herpetic dendrite. Can be seen with Woods lamp
treated as viral or bacterial conjunctivitis
• Corneal epithelial dendrites (linear branching
Treatment lesions with terminal bulbs) can be seen with
• Conservative monitoring may be appropriate fluorescein stain (Fig. 17.2)
• Surgical excision, cryotherapy, and curettage
may be therapeutic but require general anes- Diagnosis
thesia in the pediatric population • Based on the clinical findings
• HSV corneal disease will usually have sig-
nificant pain
Herpes Simplex Virus (HSV) • In atypical cases, culture, ELISA, or poly-
merase chain reaction (PCR) testing can be
Conjunctivitis
used to confirm the diagnosis
Causes
Treatment
• HSV type 1 or 2
• If HSV conjunctivitis or corneal involvement
• Most cases of primary eye involvement are
is suspected, immediate referral to an oph-
caused by HSV-1 and are associated with gin-
thalmologist is recommended
givostomatitis or recurrent orolabial infection
• Oral antivirals (e.g., acyclovir)
(cold sores)
• Topical antiviral therapy (e.g., trifluridine 1 %
• HSV-2 is associated with genital infection
drops, ganciclovir ophthalmic gel) is less fre-
and is a more common cause of neonatal HSV
quently used due to toxicity
eye infections transmitted via direct contact
• NOTE: The use of steroids alone in herpetic
in the vaginal canal during birth
infections is contraindicated
• Children with a history of HSV-related eye
Clinical presentation disease should always seek care for any future
• Concurrent herpetic skin vesicular eruption, cases of “pink eye,” as the rate of recurrence
usually somewhere on the face is high
• Unilateral follicular conjunctivitis • Given the higher than adult recurrence rate
• Palpable preauricular lymph node for corneal herpetic infections, oral prophy-
• Ocular infection can affect the eyelids, con- laxis for 1 year after the initial infection
junctiva, or cornea should be considered
Chemical Conjunctivitis topic (Seasonal) Allergic

A
Conjunctivitis
Background
• Acute noninfectious conjunctivitis after Background
chemical exposure • Immunoglobulin E (IgE)-mediated immedi-
ate hypersensitivity reaction
Clinical presentation • Dust, molds, spores, pollens, and animal dan-
• Acute onset of pain der are common triggers
• History of chemical exposure: Cleaners, pool
chlorine, some medications, etc. Clinical presentation
• Usually red eye; however, severe injuries may • Itching
actually have white eyes • Conjunctival chemosis, which manifests as
• Photophobia or decreased spontaneous open- pale edema; eyelid edema
ing of the affected eye(s) • Watery discharge
• Giant papillae assume a flat top appearance,
Diagnosis often described as “cobblestone papillae”
• Clinical findings and history of exposure are (Fig. 17.3)
nearly pathognomonic
• pH test of the eye should be performed Treatment
• Should be based on severity of symptoms
Treatment • Allergen avoidance
• Primary goal is to stop further injury • Cold compresses
• Neutralize pH through irrigation • Artificial tears
• Referral to ophthalmologist for further evalu- • Topical antihistamines or mast cell stabilizers
ation and treatment • Systemic antihistamines
Parasitic Conjunctivitis
Background
• Pediculosis may cause a follicular conjuncti-
vitis in adults with pubic lice
• Intense itching of the eyelids
• Conjunctival and lid margin injection
• Know that pubic lice (Pthirus pubis) and nits
in the cilia (eyelashes) in children are due to
sexual abuse unless proven otherwise
Management
• Referral to an ophthalmologist
• Ophthalmic ointment (e.g., erythromycin) to Fig. 17.3 Allergic conjunctivitis. Multiple giant papillae in
the superior tarsus. (Courtesy of Violeta Radenovich MD,
smother the lice MPH, Children’s Eye Center; Department of Ophthalmology,
• Pediculicide lotions and shampoos should Texas Tech University, El Paso, Texas)
also be applied
• Topical nonsteroidal anti-inflammatory • Systemic arthritis (Still’s disease) has the

agents in nonresponsive cases least propensity for ocular involvement
• Selective use of topical corticosteroids for
severe cases treated by an ophthalmologist Clinical presentation
• Allergic rhinitis and asthma are often present • May be asymptomatic
as well and must be treated accordingly • Pain
• Severe cases may benefit from referral for • Photophobia
allergy testing • Unilateral or bilateral eye redness
• Normal to decreased vision
Anterior Uveitis Management

• Symptomatic patients should be referred to
Background ophthalmology
• Uveitis usually associated with systemic dis- • Topical steroids
eases, e.g., • Topical cycloplegics
–– Juvenile idiopathic arthritis (JIA) • Systemic steroids or immunobiologics
–– Sarcoidosis
–– Kawasaki syndrome Screening
–– Reiter syndrome • All children with JIA should be referred for
–– Herpes routine ophthalmologic screening, which can
–– Syphilis be as often as every 3 months per current
–– Lyme disease guidelines [3]
–– Idiopathic • Any child with a history of JIA and complain-
–– Trauma ing of a red eye or diagnosed with pink eye
should be referred to ophthalmology for
Clinical presentation urgent evaluation
• Conjunctival injection • The highest-risk JIA subgroup for ocular
• Pain involvement is antinuclear antibody (ANA)-
• Tearing positive oligoarthritis
• Photophobia
• Decreased vision
Preseptal Cellulitis
Management
• Refer to ophthalmologist Background
• Topical steroids • Infection of periorbital soft tissues anterior to
• Cycloplegic agents the orbital septum
• Treat the underlying cause • Usually results from extension of external
ocular infections such as:
–– Hordeolum (stye)
Juvenile Idiopathic Arthritis (JIA) –– Dacryocystitis/dacryoadenitis
–– Rhinosinusitis
Background –– Dental abscess
• Ocular involvement in JIA is common –– Insect bite
• JIA-related uveitis can cause permanent –– Post-traumatic puncture, laceration, or abra-
vision loss sion of the eyelid skin. Direct penetrating
• Uveitis may be presenting sign for JIA or injury to the orbit and hematogenous seeding
may be caught on ocular screening exams in –– Severe conjunctivitis
these cases –– Skin infections: Impetigo or herpes zoster
Causes • Fever
• Staphylococcus and streptococcus have
become the two most common (75%) patho- Diagnosis
gens responsible for pediatric orbital cellulitis • CT scan with intravenous (IV) contrast is
the most important diagnostic test distin-
Clinical presentation guishing preseptal from postseptal (orbital)
• Erythema cellulitis
• Eyelid swelling
• No limitation of eye movement Management
• The globe should be white and essentially • IV antibiotic therapy should have empiric
unaffected coverage against staphylococcal and strepto-
• Eyelids can be severely swollen, causing dif- coccal species
ficulty in spontaneous opening • Vancomycin or clindamycin (MRSA) plus a
second- or third-generation cephalosporin is
Diagnosis a reasonable initial regimen
• Clinical • Orbital cellulitis requires antibiotic therapy
• No imaging studies are necessary for a total of 10–14 days
• Mucormycosis can occur in patients with dia-
Management betic ketoacidosis or severe immunosuppres-
• Choice of antibiotic depends on the source of sion and is often fatal
infection, e.g., –– The treatment should include debridement
–– Dental abscess: Cover for anaerobes, e.g., of necrotic and infected tissue plus ampho-
clindamycin or amoxicillin–clavulanate tericin B
–– Insect bite or stye: Cover for staph, e.g., • Urgent consult to ophthalmology and
first-generation cephalosporin otorhinolaryngology
–– Sinusitis: Cover for S. pneumoniae, e.g.,
high-dose amoxicillin–clavulanate, oral Complications
second- or third-generation cephalosporins • Cavernous sinus thrombosis is the most
• Admit to hospital children who do not respond serious complication
to oral antibiotics • Loss of vision and meningismus or meningi-
tis may be late complications
Orbital Cellulitis
Hordeolum (Stye) and Chalazion
Background
• Infection of orbital soft tissue posterior to HORDEOLUM
orbital septum • Acute focal infection (usually staphylococ-
• The most common association is ethmoid cal) involving the glands of Zeis or the hair
sinusitis follicle
Clinical presentation CHALAZION

• Orbital pain • Granulomatous inflammation of the meibo-
• Severe swelling mian glands that results from the obstruction
• Chemosis of the gland duct and is usually in the midpor-
• Proptosis tion of the tarsus or eyelid away from the lid
• Ophthalmoplegia: Limited ocular movement border
• Decreased visual acuity
Clinical Presentation • If patient does not respond to conservative

• Hordeolum therapy, consult with an ophthalmologist
–– Local, tender, erythematous swelling on • Incision and drainage and/or steroid injection
the eyelid margin (Fig. 17.4) is indicated if the hordeolum is large or if it is
• Chalazion refractory to medical therapy and is done by
–– Firm, tender, or nontender swelling of the the ophthalmologist
eyelid (Fig. 17.5) • Most surgical cases require general anesthe-
–– Eye discomfort, if large or internal sia in pediatric patients
–– May cause refractive errors and possible
amblyopia if chronic
Nasolacrimal Duct Obstruction
Management is the same for both hordeolum (Congenital Dacryostenosis)
and chalazion
• Frequent warm compresses Background
• Topical antibiotics (eye drops or ophthalmic • Tearing and mucoid or mucopurulent dis-
ointment) if associated infection charge, often noticed to be worse after sleep-
• Oral antibiotic if complicated by preseptal ing as the mucus can cause eyelids to stick
cellulitis together
• Normal conjunctiva, but they may develop
acute inflammation
• Digital pressure near medial canthus results
in retrograde discharge of mucopurulent
material
• Congenital glaucoma must be ruled out by
history and physical examination. Classic
triad of photophobia, tearing, and blepharo-
spasm (involuntary hard blinking)
Management
• Digital massage of the lacrimal sac
Fig. 17.4 A 5-year-old with tender erythematous subcuta- • Topical antibiotics if conjunctivitis, e.g., ery-
neous nodule near the eyelid margin thema and exudates
• Duct probing in persistent cases
• Most cases (> 90%) will self-resolve by
1 year of age
• Early probing reduces the duration of bother-
some symptoms and the potential of chronic
infections
When to refer
• If persists to 1 year of age; however, in some
areas, the ophthalmologist may prefer to per-
Fig. 17.5 Chalazion in the right lower eyelid. (Courtesy of form early in-office probing at an earlier age
Violeta Radenovich MD, MPH, Children’s Eye Center; • If develops dacryocystitis, will require IV
Department of Ophthalmology, Texas Tech University, El antibiotics
Paso, Texas)
Congenital Ptosis Management

• Any child with ptosis requires full ophthal-
Background mologic evaluation and possibly neurologic
• Congenital droopy eyelid from birth referral if concerns for systemic involvement
• Isolated abnormality of levator muscle in one
or both eyelids
Anisocoria
• Droopy eyelid since birth (Fig. 17.6) Background
• The child compensates by lifting the chin or • Difference in the size of the pupils
the forehead/eyebrow muscles • May be harbinger of significant neurologic
• Often associated with strabismus and disease
anisometropia
Causes
• Amblyopia may occur
• Small differences (1 mm or less) may be
Management physiologic and of no consequence
• Ophthalmology evaluation is important • Aneurysm affecting cranial nerve III
within the first few months of life • Horner syndrome: Neuroblastoma, mediasti-
• Surgical correction if causing occlusion nal tumors, brainstem lesions
amblyopia • Pharmacologic pupil change
• If complete ptosis after a few days of life, • Adie tonic pupil
urgent ophthalmology consultation is required
Management
• Measure size of pupils in light and in dark
Acquired Ptosis • Neurologic evaluation to exclude any other
neurologic involvement
Causes • Referral to an ophthalmologist for neuro-
• Horner syndrome; ptosis, miosis, anhidrosis ophthalmologic evaluation
• Myasthenia gravis • Urgent referral for any patients with anisoco-
• Kearns–Sayre syndrome (progressive exter- ria and additional neurologic deficits such as
nal ophthalmoplegia, pigmentary retinopathy, third nerve palsy
and cardiac conduction abnormalities)
• Orbital tumor
Coloboma
• Third cranial nerve palsy
• Neurofibroma from neurofibromatosis Background
• Leigh syndrome • Incomplete closure of the embryonic fissure
• May be found in association with systemic
syndromes or in isolation
• CHARGE syndrome (coloboma of the eye,
heart defects, atresia of the choanae, retarda-
tion of growth and development, and ear
Fig. 17.6 Congenital ptosis of the right eye. Drooping eye- abnormalities and deafness) is the most com-
lid covering part of the pupil. (Courtesy of Violeta Radenovich mon multisystem disease associated with
MD, MPH, Children’s Eye Center; Department of coloboma
Ophthalmology, Texas Tech University, El Paso, Texas)
Clinical findings
• Timing of incomplete closure determines the
extent of involvement
• Early failure of closure leads to more poste-
rior involvement with the retina or optic nerve
being involved or possibly complete
microphthalmia
• Late failure may result in an isolated iris col-
oboma (keyhole appearance)
• Effect on visual acuity can be none to severe,
depending on structures involved
Management
• Referral to an ophthalmologist for complete
Fig. 17.7 Skin appearance of Sturge–Weber syndrome
ocular examination to determine extent of
coloboma and evaluation of visual function Conditions associated with glaucoma
• Treatment will be aimed toward minimizing • Sturge–Weber syndrome (Fig. 17.7)
amblyopia; however, those with more exten- • Intraocular hemorrhage (hyphema)
sive colobomas will likely continue to have • Inflammation or tumor
profound vision loss • Aniridia (WAGR syndrome—Wilms tumor
• No current therapies are available to repair (a tumour of the kidneys), aniridia (absence
posterior eye colobomas of the colored part of the eye, the iris), genito-
• If unilateral involvement, protection of the urinary anomalies, and mental retardation
good eye is important • Lowe syndrome
• Aphakia
• Marfan syndrome
Congenital Glaucoma • Homocystinuria
• Neurofibromatosis
Definition
• Steroid treatment: Any steroid use can affect
• A progressive optic neuropathy usually
the intraocular pressure
related to intraocular pressure
• Corneal cloudiness ongenital Cataract
C
• Increased corneal diameter/large-appearing
Background
eye
• Cataracts may occur at any age
• Conjunctival injection (late finding)
• Excessive tearing, photophobia, and blepha- Causes
rospasm (eye squeezing) should alert you to • Approximately 50% of congenital cataracts
the development of glaucoma are idiopathic
• Myopia may develop as the eye elongates • Hereditary: Autosomal dominant are always
bilateral. X-linked and autosomal recessive
Management
can also occur
• Referral to ophthalmologist
• Prematurity is sometimes a cause of a cata-
• Congenital glaucoma often requires surgical
ract-like condition from remnants of the fetal
intervention as the first-line treatment
vasculature and may resolve spontaneously
• Rubella is the most common infectious cause R etinoblastoma (RB)

of congenital cataracts (TORCH syndrome—
toxoplasmosis, other agents [including HIV, Background
syphilis, varicella, and fifth disease], rubella, • RB is the most common malignant intraocu-
cytomegalovirus, herpes simplex) worldwide lar tumor in childhood
• Metabolic diseases must be considered, e.g., • Usually presents before 5 years of age
galactosemia and diabetes • One of the most common (47%) causes of
• Teratogens such as alcohol and corticoste- leukocoria in childhood
roids may also cause congenital cataracts • RB gene RB1 is passed as autosomal domi-
• Associated syndromes include trisomies 13, nant trait
18, and 21, as well as Alport, Lowe, and • Risk of recurrence is lower in unilateral than
Marfan syndromes bilateral cases of RB
Clinical presentation (Fig. 17.8) Clinical presentation

• Absent or asymmetric red reflex • Leukocoria and strabismus are the most com-
• Any irregularity or asymmetry of the pupils mon presenting findings
• Dark spots in the red reflex • Average age at the time of diagnosis is 2 years
• White reflex in unilateral cases and 1 year in bilateral cases
• Occasional nystagmus
Diagnosis
Management • Magnetic resonance imaging (MRI) and
• Immediate referral to a pediatric ultrasound are the best diagnostic testing,
ophthalmologist often noting calcification within the mass
• Optimally, surgical intervention for unilateral
congenital cataracts should occur within Management
6 weeks and bilateral cases within 10 weeks • All children with a new leukocoria should be
[4] referred to an ophthalmologist
• Primary systemic chemotherapy (chemore-
duction) followed by local therapy (laser pho-
tocoagulation, cryotherapy, thermotherapy,
or plaque radiotherapy), or even enucleation
(surgical removal of the eye), depending on
the stage of the disease (Fig. 17.9)
• Intra-arterial chemotherapy is a new modality
of treatment in certain cases
• Immediate referral to an ophthalmologist and
subsequently an oncologist after diagnosis
confirmation
Papilledema
Background
• Papilledema is a swelling of optic discs sec-
Fig. 17.8 Central cataract in a 4-month-old child ondary to increased intracranial pressure
a b
Fig. 17.9 (a) Retina photo showing large retinoblastoma cov- Radenovich MD, MPH, Children’s Eye Center; Department of
ering part of the optic nerve. (b) Retinoblastoma after systemic Ophthalmology, Texas Tech University, El Paso, Texas)
chemotherapy and laser therapy. (Courtesy of Violeta
a b
Fig. 17.10 (a) Normal optic disc with sharp margins and (Courtesy of Violeta Radenovich MD, MPH, Children’s Eye
pink rim. (b) Fundus photograph showing optic nerve edema Center; Department of Ophthalmology, Texas Tech
due to elevated intracranial pressure in the right eye, periph- University, El Paso, Texas)
eral elevation of nerve, and blurred disc margins (arrow).
Causes • Blurred margins of optic disc (Fig. 17.10a)

• Hydrocephalus, mass lesion, neuroblastoma, showing normal optic disc with sharp margin
meningitis, or idiopathic intracranial hyper- for comparison (Fig. 17.10b)
tension (IIH), aka Pseudotumor cerebri
Management
Clinical presentation • Head imaging computed tomography (CT)/
• Severe headaches with possible nausea and MRI must be performed
vomiting • MRI/magnetic resonance venography (MRV)
• Cranial nerve palsies are usually a late sign is better for IIH and some other processes;
• Esotropia and double vision may result from however, CT may be faster to obtain and can
cranial nerve VI paralysis, which is the most rule out many emergent diagnoses in urgent
likely involved oculomotor nerve due to its situations
anatomic course • If CT is negative, lumbar puncture should be
• Transient visual obscurations performed for possibility of IIH
Optic Neuritis • Treatable forms of RP can be found in abet-

alipoproteinemia (Bassen–Kornzweig),
Background phytanic acid oxidase deficiency (Refsum
• Optic neuritis implies an inflammatory pro- disease), and familial isolated vitamin E
cess involving the optic nerve deficiency
• Most cases of optic neuritis in children are
due to an immune-mediated process Clinical presentation
• Usually presents initially in adolescence
Causes • Complaints of difficulty with night vision
• Presents often after systemic infections such (seeing stars, difficulty in movies)
as measles, mumps, chicken pox, and viral • Visual acuity can remain normal for many
illnesses years
• Vaccinations have been associated with onset • Progressive peripheral visual field loss lead-
due to upregulation of the immune system. ing to tunnel vision and blindness
• It can occur as an isolated neurologic deficit • Classic triad: Pigmentary retinopathy (“bone
or as component of more generalized neuro- spiculing”), waxy pallor of the optic nerve,
logic disease, such as acute disseminated and retinal vessel attenuation
encephalomyelitis, neuromyelitis optica, or • Cataracts may also be seen
multiple sclerosis
Treatment
Clinical presentation • No definitive treatment exists
• Vision loss, can be asymmetric • Vitamin A supplementation may be beneficial
• Decreased color vision • Referral to low vision specialist at time of diag-
• Painful eye movements nosis allows a child to learn how to use low
• Optic disc edema vision aids prior to losing vision (e.g., Braille)
• Afferent pupillary defect if asymmetric • Some forms are amenable to gene therapy
involvement
Management etinal Hemorrhage

R
• Brain and orbital MRI with addition of spinal
MRI if peripheral neuropathy present Background
• Consider lumbar puncture • Bleeding within the layers of the retina
• Intravenous steroids should be considered in • Can be asymptomatic or cause profound
order to hasten visual recovery but does not vision loss, depending on location and type
lessen the risk of recurrence • Location and appearance of hemorrhages can
give clue as to cause
Retinitis Pigmentosa (RP) [5] Causes

• Trauma, in particular nonaccidental
Background • Birth via vaginal delivery and occasionally
• Progressive vision loss starting in childhood C-section can sometimes produce small, self-
from loss of photoreceptor function resolving hemorrhages
• One in 4000 worldwide prevalence • Roth spots (retinal hemorrhages with white
center) can be seen most commonly in leuke-
Causes mia or bacterial endocarditis
• Inherited in dominant, recessive, and X-linked • Retinopathy of prematurity (ROP) or
forms regressing fetal vasculature in neonates
• Sometimes associated with Usher or Bardet– (Fig. 17.11)
Biedl syndromes
Retinal Hemorrhages Retinopathy of Prematurity (ROP)

in Nonaccidental Trauma
Background
• Scattered to diffuse retinal hemorrhages in • Vasoproliferative disease of the retina medi-
multiple layers of the retina (Fig. 17.12) ated through the release of vascular endothe-
lial growth factor (VEGF)
Treatment • ROP is a disease of the retina in a premature
• Varies based on type and severity infant due to neovascularization: Fragile ves-
• Close monitoring sels that break, bleed, and form scar tissue
• Head of bed elevation is useful in some cases causing retinal detachment and blindness
• Intraocular surgery may be necessary in • First described in preterm infants
severe cases • Annually, a total of 15 million infants are
• Attempts should be made to photo document born premature worldwide, 1 in 10 [6]
these cases due to the legal ramifications • Annually, an estimated 50,000 children go
blind secondary to ROP worldwide [7]
Causes
• First epidemic
–– 1940s and 1950s
–– Primary cause: oxygen unmonitored
–– Few small (750–1000 g) infants survived
(< 8 %)
• Second epidemic
–– 1970s to present
–– Oxygen closely monitored
–– Primary cause: Many small (500–1000 g)
infants survived (> 80 %)
• Third epidemic
–– 2000s to present
Fig. 17.11 Boat-shaped retinal hemorrhage secondary to
regressed fetal vasculature • Primary cause: Oxygen unmonitored
a b
Fig. 17.12 (a, b) Diffuse retinal hemorrhages in various layers of the retina. Some hemorrhages have white central dot
a b
Fig. 17.13 Retinopathy of prematurity (ROP). (a) Retina early stage 3, posterior to the ridge. (Courtesy of Violeta
photo showing stage 2 ROP or ridge. (b) Retina photo show- Radenovich MD, MPH, Children’s Eye Center; Department
ing popcorn disease, small extravascular fibroproliferation or of Ophthalmology, Texas Tech University, El Paso, Texas)
• Many infants (750–2000 g infants) survived

(> 90%)
• ROP is multifactorial
• Smallest, most immature, and sickest infants
in NICU are at the highest risk
Risk factors
• Low birth weight
• Low gestational age
• Hypoxia
• Hyperoxia
• Oxygen fluctuations
• Blood transfusions
• Intraventricular hemorrhage Fig. 17.14 Retina photo showing sectorial plus disease,
• Bronchopulmonary dysplasia mild dilation, and tortuosity of central retina vessels.
• Sepsis (Courtesy of Violeta Radenovich MD, MPH, Children’s Eye
• Necrotizing enterocolitis Center; Department of Ophthalmology, Texas Tech
University, El Paso, Texas)
• Infant of a diabetic mother
Complication of ROP Current management

• Mild/transient to severe proliferative neo- • Prevention: Appropriate oxygenation and
vascularization with scarring, retinal detach- nutrition
ment, and blindness (Figs. 17.13 and 17.14) • Robust screening program
Initial retinal screening [8] Screening Descriptions [9]

• Premature infants of 30 weeks gestation or less • 3 zones
• Birth weight of 1500 g or less –– Zones are annotated I, II, and III with I
• Older or heavier infants with an unstable clin- being the zone that is most posterior and
ical course or believed by the pediatrician to includes the optic nerve
be at high risk • Six stages
• Examination at 4 weeks postnatal age or –– Stages are annotated 0 through 5 with 0
31 weeks adjusted age (whichever is later) being immature vessels and 5 indicating a
a b
Fig. 17.15 Retinal photo showing aggressive posterior reti- tion at the terminal ends of the vessels. (b) Same patient
nopathy of prematurity. (a) Note extensive vessel dilation 1 week after treatment with bevacizumab injection into the
and tortuosity in the posterior pole with flat neovasculariza- vitreous
total retinal detachment (best ➔ worst visual anesthesia; however, the medication does
prognosis) become systemic. Early data suggest that
• Plus disease: An additional descriptor relat- there are no systemic or neurologic deficits
ing to presence of central retinal venule dila- due to this systemic absorption; however,
tion and arteriolar tortuosity studies are ongoing
• Aggressive posterior ROP (AP-ROP). An • Blindness due to ROP can often be prevented
aggressive form of ROP that is seen in the with adequate nutrition, oxygenation, and
most posterior zone and portends a poor out- timely treatment
come even if treated (Fig. 17.15) • Despite being vision-saving, the treatment for
ROP, as well as the disease itself, will often
Treatment programs lead to high myopia, strabismus, and other
• Goal of treatment is to downregulate release ocular conditions throughout life
of VEGF to reduce neovascularization
• Laser surgery has overtaken cryotherapy as
the mainstay of treatment EYE TRAUMA [10]
• Anti-VEGF therapy
• Retinal surgery for those infants with retinal Background
detachments • Eye trauma can lead to permanent vision loss
• 840,000 cases of pediatric ocular trauma
Early treatment occur yearly in the USA
• Laser ablation to peripheral avascular retina • Can be broadly defined as open-globe or
to prevent retinal detachment by pediatric closed-globe injury
ophthalmologist or retina specialist • Prevention saves vision. Encourage protec-
• Anti-VEGF therapy (bevacizumab) is becom- tive eyewear
ing more widespread and has shown to have
good outcomes, especially for those children Evaluation
with very posterior disease (zone 1) • Visual acuity: Presenting visual acuity is a
• The injection of anti-VEGF medications fre- key factor in predicting final visual outcome
quently does not require sedation or general • Pupil size, shape, and reactivity
• A tadpole-shaped pupil is a sign of an open Diagnosis

globe • Requires the use of a slit lamp microscope to
evaluate anterior chamber cell and flare
Open-globe injuries
• Penetrating injury to the eye Management
• Tend to have a poorer visual acuity outcomes • Referral to ophthalmologist
• Must be ruled out in any trauma to the eye • Topical steroid and dilating drops
• Mechanism of injury and abnormal pupil • Frequent evaluation until resolved
shape are quickly available for assessment
• If an open-globe injury is suspected, emer-
gent referral to an ophthalmologist is Retinal Detachment
indicated
• If an open-globe injury is suspected, consider Background
administering a broad-spectrum antibiotic • Occurs when the retina separates from its
and making patient non per os (NPO) underlying supporting tissue, the choroid
• Spontaneous detachments in children are rare
Closed-globe injuries
• Any injury to the eye not resulting in open Causes
globe • ROP
• Corneal abrasions, hyphema, burns, conjunc- • Trauma
tival laceration • High myopia
• If appropriately treated, usually have favor- • Diabetes
able visual outcomes • Sickle cell disease
• Stickler syndrome
Treatment • Marfan syndrome
• Referral to ophthalmologist. If concern for
open globe, then shield the eye and consult Clinical presentation
• Dark curtains, floaters, and flashes of light are
possible presenting complaints
Traumatic Iritis • Preverbal and early verbal children may not
be able to express symptoms
Background • Preverbal and nonverbal children may display
• Inflammation in the front chamber of the eye reactionary signals of vision change such as
• Most commonly seen with a history of blunt poking the eye (oculodigital reflex) or rub-
trauma bing the eye
• Visual acuity may be completely intact
Clinical presentation • Red reflex may be abnormal if retinal detach-
• History of trauma ment involves the central retina
• Photophobia (can be severe)
• Conjunctival injection, usually 360° Management
• Variable vision, but usually at least slightly • Immediate referral to ophthalmologist
decreased in affected eye • Retinal detachments require surgery. Can be
• No corneal staining with fluorescein evaluation vitrectomy or scleral buckling, depending on
• Under high magnification with a slit lamp the type of detachment and surgeon
microscope, one can see white cells floating • Children may need amblyopia treatment fol-
in the anterior chamber lowing repair
Orbital Fracture • Discomfort with blinking, sharp pain, and

photophobia
Background • In infants, corneal abrasions can present
• Blunt trauma to the face or directly to eye as initially unexplained, inconsolable
crying
Clinical presentation • A child may be continually rubbing an eye,
• Periorbital ecchymosis which is watery and red
• Eye/face pain
• Limitation of upward gaze Diagnosis
• May have decreased ipsilateral cheek or • Topical fluorescein, which is available in
upper lip sensation paper strip or drop forms
• Epistaxis • May apply topical anesthetic in solution to
• Bradycardia from oculocardiac reflex facilitate the eye exam
• Diplopia • The area of abrasion will fluoresce under a
cobalt blue filter light (Wood’s lamp)
Diagnosis • A vertically oriented abrasion may herald a
• Thin-cut coronal CT of the orbit is the best foreign body under the eyelid
imaging study
• Associated globe injury 10–50 % Management
• Orbital floor is most common fracture • Topical eye antibiotic ointment, for example,
• Beware the white-eyed blowout fracture, which erythromycin or bacitracin ophthalmic,
presents with minimal eye redness, but has a should be applied four times daily to prevent
“trapdoor” or a greenstick fracture of the orbital infection
floor, which can cause subtle findings on CT • Ointment is preferred, as it creates a lubricat-
ing effect; however, it also blurs the vision
Management much more than topical drops
• Discourage blowing of nose. Give nasal • Antibiotics are continued until the epithelial
decongestants defect is closed
• Must be evaluated by facial trauma team • Daily examination is recommended for
(ophthalmology, ENT, plastic surgery, maxil- children
lofacial surgeon, or others, as standard in par-
ticular location) Important to know
• If primary team is not ophthalmology, then • Corneal abrasions heal rapidly, often within
will also require ophthalmologic evaluation 24 h for smaller injuries
• Surgical repair is not indicated in every case; • Patients who wear contact lenses or have a
many are managed conservatively history of ocular herpes should be referred
• Bradycardia, nausea, and vomiting are signs urgently to an ophthalmologist for
of muscle entrapment, which may require consultation
urgent surgical intervention • The usual recommendation is to avoid con-
tact lenses until the injured eye has felt nor-
mal for at least 1 week
Corneal Abrasion • Patients with large or central abrasions should
Clinical presentation be referred to an ophthalmologist
• Eye tearing • The use of patching should be avoided unless
• Foreign body sensation directed by an ophthalmologist
Eye Foreign Body Management

• Bed rest with elevation of the head of the bed
Clinical presentation and eye shield on the affected eye
• Sudden onset of eye pain after exposure, par- • Emergent ophthalmology consultation
ticularly with flying debris or wind • May require admission if unable to reliably
• Associated with intraocular foreign body in complete bed rest
18–41% of cases • Sickle cell disease status should be tested in
high-risk populations due to the association
Diagnosis of complications
• History and physical exam
• Topical anesthetic will facilitate the exam Complications
• Fluorescein exam • Internal corneal staining
• Evert the upper eyelid at exam. Foreign bod- • Increased intraocular pressure, which can
ies (FBs) tend to hide under the upper eyelid cause glaucoma and optic nerve damage if
• Retract the lower eyelid to inspect the inferior untreated
conjunctiva • Cataract
• Orbital CT scan, if intraocular FB is
suspected
STRABISMUS
Management
• Best initial management is gentle eye irriga- Background
tion or gentle swabbing • Strabismus is a misalignment or deviation of
• Eye irrigation can be performed by hanging the eye or deviation; it may be congenital or
an IV and holding the tubing over the eye. acquired
Irrigating contact lenses can cause more • -Tropia: Deviation with binocular viewing,
injury in some cases may be intermittent or constant (e.g., red
• Refer to ophthalmology any patient with an reflex, cover–uncover testing)
intraocular FB when FB cannot be removed • -Phoria: Deviation present only when binocu-
or has caused large corneal abrasion or if dis- lar viewing is interrupted (e.g., alternate cover
coloration of tissue is noted after the FB is testing)
removed • Esotropia is an inward deviation (Fig. 17.16)
• Exotropia is an outward deviation
(Fig. 17.17)
Hyphema • Hypertropia is an upward deviation
• Hypotropia is a downward deviation
Background
• Hyphema is blood in the anterior chamber Congenital esotropia
usually after blunt trauma • Onset within first 6 months of age
• Paintballs, small foam missiles, other projec- • Associated with large-angle strabismus and
tiles like bungee cords are common causes usually a constant deviation
• Amblyopia in 50% of patients
Clinical presentation • Poor stereovision (includes depth
• Blurring of vision to complete loss of vision perception)
• Photophobia • Treatment: Early referral to ophthalmologist
• Eye pain is common with surgery within first 12 months of life
a b
Fig. 17.16 (a) External photo showing right eye esotropia or crossing. (b) External photo showing recentration of corneal
light reflex through the use of prism to measure amount of esotropia, in this case 35 prism diopters (Krimsky test)
Vertical misalignment
• Congenital fourth nerve palsy is the most
common nontraumatic cause in children
• May be cause of torticollis that is not respon-
sive to physical therapy
Fig. 17.17 External photo showing right eye exotropia, out- • Orbital floor fracture can cause hypotropia,
ward deviation. (Courtesy of Violeta Radenovich MD, MPH, worse on attempted upgaze
Children’s Eye Center; Department of Ophthalmology,
Texas Tech University, El Paso, Texas)
Pseudostrabismus
Accommodative esotropia • An appearance of esotropia when one does
• Onset usually between 3 and 5 years of age not actually exist
• Directly related to hypermetropia (i.e., • Frequently seen in children with wide nasal
farsightedness) bridges or large epicanthal folds
• Attempt to accommodate to see clearly causes • Diagnosis: Central corneal light reflex. No
the eyes to cross misalignment on cover testing
• Typical crossing at near is greater than at
distance Diagnosis
• Treatment: Full-time wear of eyeglass • Visual acuity test, cover test, light reflex test
correction • Corneal light reflex (Hirschberg) is a good
• Some subtypes require bifocals or surgery in initial testing
addition to the eyeglasses • An asymmetric red reflex may indicate stra-
bismus with the brighter eye having
Intermittent exotropia misalignment
• Most commonly occurring between ages 2 • The best test to differentiate heterophoria
and 8 years from heterotropia is cover–uncover test
• Patient may squint one eye
• Treatment is to correct any refractive error Remember
with eyeglasses, and some may require stra- • Occasional eye deviation in newborns can be
bismus surgery observed; if it persists beyond 4 months, should
• Patching therapy may help in some cases be referred to pediatric ophthalmologist
• Refer to pediatric ophthalmologist all patients • Vision screenings in children under five are
with strabismus very important
• Occlusion therapy is more effective under the
Critical to know age of 8 but can still be done in older children
• New-onset strabismus can be a manifestation • Studies in older children with amblyopia have
of eye or brain tumor and should be investi- shown that treatment can still be beneficial
gated immediately beyond the first decade of life, especially if
• Amblyopia is a common complication in never treated previously
untreated cases • Compliance can be a problem with children
• Strabismus is treated by the ophthalmologist
with eyeglasses, patching, or surgery
VISION DEVELOPMENT
Amblyopia AND VISUAL ACUITY [11, 12]
• Visual pathways begin to develop around the
Background
day 23 of gestation
• A unilateral or bilateral reduction of best-cor-
• Ocular lens placode develops by day 27
rected visual acuity that cannot be attributed
• Embryonic fissure of the optic stalk closes by
directly to the effect of any structural abnor-
day 33 (important for colobomas)
mality of the eye or the posterior visual
• The fovea (retinal anatomy responsible for
pathways
best vision) starts to differentiate at around
• It is a consequence of diminished visual input
15–17 weeks and continues through 32 weeks
into the visual cortex, which leads to impair-
• Myelination of optic nerve starts at approxi-
ment of neuro-ophthalmologic pathways
mately 7 months and continues after term
Causes birth
• Strabismus (the most common cause) • Visual acuity matures somewhere between
• Anisometropia (unequal refractive errors) or ages 5 and 15
high refractive errors • Eye alignment should be consistently straight
• Stimulus deprivation: Cataracts, corneal opac- after 3–4 months of age
ities, vitreous hemorrhage, lid hemangiomas • Infants can differentiate shape and size by
4.5 months and contours/edges by 6 months
Diagnosis of age
• Vision screening
Management DISORDERS OF REFRACTION

• Patients who failed vision screening need to
be referred to an ophthalmologist • Types: Myopia (nearsighted), hyperopia (far-
sighted), astigmatism
Ophthalmology treatment • Without adequate screening programs for
• Eliminate any obstacle to vision such as children, can easily be missed
cataracts • Unless objectively evaluated, children may
• Correct any refractive errors not complain of any subjective visual diffi-
• Patching or occlusion therapy. Atropine eye culties for many years
drops may be used in some cases • Uncorrected refractive error can cause diffi-
• Amblyopia should be detected early culty in school
• Uncorrected refractive errors can cause –– Anomalous head position often leads to a
permanent vision loss through amblyopia if slowing of the eye movements (null point)
not diagnosed and referred in early –– Surgery is indicated to correct the head
childhood position and slow the eye movements
• Screening visual acuity should occur at yearly
well-child visits beginning at age 3 [1] Congenital sensory nystagmus
• Referral criteria is based on age of child: • Horizontal nystagmus, sometimes pendular
–– Age 3–4: 20/50 or worse • Begins in the first 3 months of life
–– Age 4–5: 20/40 or worse • Associated with ocular abnormalities that
–– Over 5: 20/32 or worse may affect visual development: Bilateral cat-
–– Any age: Asymmetry between the two eyes aracts, glaucoma, corneal opacities, aniridia,
retinal dystrophy, optic nerve hypoplasia,
Contact lens-related problems foveal hypoplasia
• Sleeping in contact lenses exponentially
raises risk of infection Acquired nystagmus
• A red eye with a lesion on the cornea (seen • Brain imaging is necessary to rule out any
best with fluorescein and magnification) in a intracranial lesions
patient with contact lens use needs immediate
Spasmus nutans
referral to an ophthalmologist
• Bilateral nystagmus, horizontal, vertical, or
• Broad-spectrum ophthalmic antibiotics (e.g.,
rotary
topical moxifloxacin) is a commonly used
• Abnormal head movement (nodding or bob-
option for contact lens-related ulcers/
bing) or torticollis
keratitis
• Rarely starts before 4 months of age
• MRI to rule out chiasmal or suprachiasmatic
tumors (glioma)
Nystagmus
Management
Background • Children with nystagmus need to be referred
• Nystagmus is involuntary rhythmic eye to a pediatric ophthalmologist
movement
• May signify important eye or central system
pathology ORBITAL MASSES
• Can be hereditary
• Any internal eye problem can cause sensory P eriorbital Tumor or Hemangioma
nystagmus, e.g., cataract, optic atrophy or
aniridia, corneal opacities, retinal dystro- Background
phies, optic nerve hypoplasia, etc. • Periorbital masses may cause vision loss
through ptosis or compressive mechanisms
Clinical presentation • May be isolated or a harbinger of systemic
• Infantile nystagmus syndrome usually before disease
2 months • Many causes: Neurofibroma, hemangioma,
–– Horizontal, jerky oscillations, bilateral dermoid cyst, neuroblastoma, tumor
–– Visual function is highly variable from
normal to significantly impacted Clinical presentation
–– It is not associated with other central ner- • Ptosis—usually unilateral
vous system abnormalities • Proptosis
• Increased resistance to retropulsion PEARLS AND PITFALLS

• Asymmetric astigmatism
• Neuroblastoma can present as sudden-onset • Visual acuity screening with linear testing
eyelid ecchymosis methods should be attempted at age 3 years.
• Vision screening is important, as many vision
Treatment problems become more difficult or impossible
• Urgent MRI for concern of neuroblastoma to improve as children approach age 8 years.
• Referral to ophthalmologist • Ophthalmia neonatorum is a vision-
• Treat amblyopia threatening process in which the timing of
• Hemangioma: Consider topical or oral onset can help provide clues to the diagnosis.
beta-blocker • Ocular involvement in juvenile idiopathic
• Possible surgical excision arthritis may be asymptomatic, and children
should have routine screening exams.
• Congenital glaucoma must be ruled out in
Orbital Rhabdomyosarcoma [13] cases of excess tearing such as nasolacrimal
duct obstruction and can possibly be identi-
Background
fied through a classic triad of tearing, photo-
• Highly malignant neoplasm of embryonal
phobia, and blepharospasm.
striated muscle cells
• Congenital cataracts have a variety of etiolo-
• Orbital involvement is one of the most com-
gies but must be identified and treated as early
mon locations, accounting for 10–20% of all
as 4 weeks of life.
rhabdomyosarcoma cases
• Retinal hemorrhages from trauma are usually
• Most common soft tissue sarcoma in
diffuse and found in multiple layers of the
children
retina.
Clinical Presentation • In evaluating for papilledema with a lumbar
• Proptosis, possibly rapidly changing puncture, the opening pressure must be care-
• Ptosis fully measured.
• Globe displacement, most frequent • The goal of treatment in ROP is to downregu-
inferotemporally late the expression of VEGF, which is now
most frequently accomplished through laser
Diagnosis treatment, with anti-VEGF injections becom-
• Orbital imaging with CT or MRI is ing an option in many centers.
mandatory • Beware of the white-eyed blowout orbital
• Biopsy should be performed promptly if a fracture. Child will present with a white eye,
mass is noted on radiographic evaluation but may have bradycardia, nausea, vomiting,
and/or diplopia. This condition requires
Management urgent surgical evaluation.
• Urgent referral to an ophthalmologist
• Treatment usually includes a combination of
chemotherapy, irradiation, and/or surgical Acknowledgment The authors gratefully
excision acknowledge the contributions of Violeta
Radenovich MD, MPH, Children’s Eye Center of 6. World Health Organization. Preterm birth.
El Paso, El Paso, Texas, to the 1st edition of this http://www.who.int/news-room/fact-sheets/
chapter, many of which have been incorporated detail/preterm-birth. Accessed 21 Sep 2018.
into this edition as well. 7. Gilbert C. Retinopathy of prematurity: a global
SLR was supported by an unrestricted grant from perspective of the epidemics, population of
Research to Support Blindness (New York, NY). babies at risk and implications for control.
Early Hum Dev. 2008;84(2):77–82.
Disclaimer The views expressed in this chapter 8. Fierson WM, American Academy of Pediatrics
are those of the authors and do not necessarily Section on Ophthalmology; American
reflect the official policy or position of the Academy of Ophthalmology; American
Department of the Navy, Department of Defense, Association for Pediatric Ophthalmology and
or the United States Government. CDR Miller is a Strabismus; American Association of Certified
military service member. This work was prepared Orthoptists. Screening examination of pre-
as part of his official duties. Title 17 U.S.C. 105 mature infants for retinopathy of prematurity.
provides that “Copyright protection under this title Pediatrics. 2013;131(1):189–95.
is not available for any work of the United States 9. International Committee for the Classification
Government.” Title 17 U.S.C. 101 defines a United of Retinopathy of Prematurity. The inter-
States Government work as a work prepared by a national classification of retinopathy of
military service member as part of that person’s prematurity revisited. Arch Ophthalmol.
official duties. 2005;123(7):991–9.
10.
Miller KE. Pediatric ocular trauma: An
update. Current Ophthalmology Reports.
References 2017;5(2):107–13.
11.
American Academy of Ophthalmology.
1. Committee on Practice and Ambulatory
Growth and development of the eye. In: AAO
Medicine, Section On Ophthalmology,American
basic and clinical science course. Pediatric
Association of Certified Orthoptists; American
ophthalmology and strabismus. San Francisco:
Association For Pediatric Ophthalmology
American Academy of Ophthalmology; 2011.
and Strabismus; American Academy of
p. 167–71.
Ophthalmology. Visual system assessment in
12. Siu CR, Murphy KM. The development of

infants, children, and young adults by pediatri-
human visual cortex and clinical implications.
cians. Pediatrics. 2016;137(1):28–30.
Eye Brain. 2018;10:25–36.
2. Azari AA, Barney NP. Conjunctivitis: a sys-
13. Shields JA, Shields CL. Rhabdomyosarcoma:
tematic review of diagnosis and treatment.
review for the ophthalmologist. Surv
JAMA. 2013;310(16):1721–9.
Ophthalmol. 2003;48(1):39–57.
3. Cassidy J, Kivlin J, Lindsley C, Nocton
J, Section on Rheumatology; Section on
Ophthalmology. Ophthalmologic examina-
Suggested Reading
tions in children with juvenile rheumatoid
arthritis. Pediatrics. 2006;117(5):1843–5. American Academy of Ophthalmology Pediatric
4. Davenport KM, Patel AA. Cataracts. Pediatr Ophthalmology/Strabismus Panel. Preferred
Rev. 2011;32(2):82–3. Review. practice pattern guidelines: pediatric eye evalu-
5. Hartong DT, Berson EL, Dryja TP. Retinitis ations. San Francisco: American Academy of
pigmentosa. Lancet. 2006;368:1795–809. Ophthalmology; 2017. p. 189–227.
American Academy of Pediatrics, Section and young adults by pediatricians. Pediatrics.

on Ophthalmology, Council on Children 2016;137(1):28–30.
with Disabilities, American Academy of Ehlers JP, Shah CP. Corneal abrasion. In: Ehlers JP,
Ophthalmology, American Association for Shah CP, editors. The Wills eye manual: office
Pediatric Ophthalmology and Strabismus, and and emergency room diagnosis and treatment
American Association of Certified Orthoptists. of eye disease. 5th ed. Baltimore: Lippincott;
Joint statement—learning disabilities, dyslexia, 2008. p. 15–6.
and vision. Pediatrics. 2009;124(2):837–44. Harrison JR, English MG. Chlamydia trachomatis
Donahue SP, Nixon CN, Section on Ophthalmology, infant pneumonitis: comparison with matched
American Academy of Pediatrics; Committee on controls and other infant pneumonitis. N Engl J
Practice and Ambulatory Medicine, American Med. 1978;298(13):702–8.
Academy of Pediatrics; American Academy Rapoza PA, Chandler JW. Neonatal conjunctivi-
of Ophthalmology; American Association for tis: diagnosis and treatment. In: Focal points
Pediatric Ophthalmology and Strabismus; 1988: clinical modules for ophthalmolo-
American Association of Certified Orthoptists. gists. San Francisco: American Academy of
Visual system assessment in infants, children, Ophthalmology; 1988. p. 5–6.
Ear, Nose, and Throat
18
EARS –– Hearing loss can present later in childhood

as conductive or mixed hearing loss
Preauricular Pits/Sinus (PPS) • PPS do not require surgical excision unless
they are frequently draining or infected
• Small indentations located anterior to the • Passing of prenatal hearing screen should be
helix and superior to the tragus confirmed in all patients
• Can occur unilaterally (~50%) or bilaterally • Audiogram should be performed if there are
(~50%) other outer ear deformities or any evidence of
• Prevalence ranges between 1% and 10% genetic syndromes
depending on ethnicity • Wang et al. [1] suggest that a renal ultrasound
• Can occur in isolation with no increased risk be performed in children with ear anomalies
of hearing impairment or renal issues accompanied by any of the following:
• Can be associated with hearing impairment –– Other known organ malformations
and organ malformations –– Family history of deafness and auricular
• Branchio-oto-renal (BOR) syndrome: and/or renal malformation
–– Most common inherited syndrome causing –– Maternal history of gestational diabetes
hearing loss (autosomal dominant) mellitus
–– Clinical presentation: preauricular pits,
sensorineural hearing loss (SNHL), bran-
chial cysts (may present as holes/pits in the O talgia
side of the neck or as tags/pits in front of
the ear), renal anomalies Definition
• Beckwith-Wiedemann syndrome: • Ear pain may be primary or referred in
–– Clinical presentation: macroglossia, asym- origin
metric ear lobules or creases, omphalocele, Clinical Presentation
Wilms tumor, hepatoblastoma. • Must consider potential sources of referred
pain as well as sources of primary ear pain
• Primary: otitis externa, foreign body, acute
K. D. Meister
Department of Otolaryngology-Head & Neck Surgery, Pediatrics
otitis media (AOM), chondritis, ear canal lac-
Division, Lucile Packard Children’s Hospital, Stanford University, eration, mastoiditis
Stanford, CA, USA • Referred: temporomandibular joint (TMJ)
A. H. Messner (*) disorders, larynx infection or pathology, deep
Professor of Otolaryngology/Head & Neck Surgery,
Baylor College of Medicine, Texas Children’s Hospital, neck space infection, cervical spine disorders
Houston, TX, USA –– Very common after oropharyngeal surgery
e-mail: annamessner@stanford.edu
(such as tonsillectomy)
612 K. D. Meister and A. H. Messner
Otitis Externa • Presentation: drainage, cough, pain, pruritus,

child pulling at ear, incidentally noted during
Definition exam
• Inflammation of the external auditory canal • Most foreign bodies do not require emergent
(EAC) due to bacterial (most commonly removal
Pseudomonas aeruginosa, followed by • Emergent removal for button batteries.
Staphylococcus species) or fungal infections • Indication for ENT referral:
–– Presence of tympanic membrane perforation
Clinical Presentation –– Foreign body wedged in the canal that can-
• Pain and tenderness with tragal pressure/pulling not be grasped
pinna; pruritic, erythematous, and edematous –– Trauma/bleeding in the ear canal
EAC; debris in the EAC; malodorous otorrhea –– Failed attempt at removal
• Differential diagnosis: necrotizing otitis
externa, otitis media with perforation, Ramsay
Hunt syndrome, furuncle, atopic dermatitis, Hematoma of the External Ear
EAC foreign body, chondritis (Pinna)
Treatment • Commonly due to trauma
• Pain control and anti-inflammatories. • Can cause avascular necrosis (blood supply
• Topical ear drops (ensured Pseudomonas lifted away from the cartilage by the hema-
coverage) toma) and permanent damage to the underly-
• Keep ears dry with water precautions (child ing cartilage (Fig. 18.1)
either should swim with a neoprene headband
to keep the ears dry or should not swim) and/
or with ear dryer (hair dryer)
• Ears drops of solution made of 50:50 white
vinegar and rubbing alcohol can provide pro-
phylaxis (if there’s no tympanic membrane
perforation). Commercial ear drops to pre-
vent swimmer’s ear are also available over
the counter
Indications for Ear, Nose, and Throat (ENT)

Referral
• Significant debris in the EAC—will require
debridement.
• If unable to visualize the tympanic membrane
due to canal edema, patient will require a
temporary ear wick
• Immunocompromised or diabetic patient
Foreign Body in the External Ear

• Beads, insects, toys, popcorn, beans, and but-
ton batteries are common ear foreign bodies. Fig. 18.1 Auricular hematoma of the right ear
18 Ear, Nose, and Throat 613
Management Management
• Urgent aspiration of hematoma to prevent • 2013 American Academy of Pediatrics guide-
pinna deformity (i.e., wrestler’s ear or cauli- lines [3]:
flower ear) –– Immediate antibiotic treatment for the
• Pressure dressing applied after evacuation following:
• Close follow-up to monitor for reaccumulation ◦◦ Children < 6 months of age
◦◦ Children with moderate to severe
otalgia
Acute Otitis Media (AOM) ◦◦ Otalgia lasting longer than 48 h
◦◦ Temperature > 39 °C (102.2 °F)
Background ◦◦ Bilateral AOM and less than 24 months
• Signs of an acute infection associated with of age
middle effusion and inflammation (bulging –– Antibiotic treatment or observation with
tympanic membrane) pain control:
• 80% of children have at least one AOM before ◦◦ 6 to 24 months of age with unilateral
1 year of age; 90% of children have at least non-severe AOM.
two AOM by the age of 3 ◦◦ > 24 months of age with unilateral or
bilateral non-severe AOM.
Risk Factors
◦◦ When observation is chosen, child must
• Age (6–18 months), positive family history of
be followed up. Initiate antibiotics
otitis media, daycare attendance, lack of breast-
within 48–72 h should the child worsen
feeding, exposure to tobacco smoke, pacifier
or fail to improve
use/bottle propping, race/ethnicity (native
Americans and the Inuit are at higher risk) [2] Antimicrobial Therapy
• First line: amoxicillin (90 mg/kg/day divided
Common Pathogen
twice a day) × 10 days
• Bacterial: Streptococcus pneumoniae, non-
• Second line, amoxicillin-clavulanate:
typeable Haemophilus influenzae, Moraxella
–– Children who failed first-line therapy
catarrhalis, and Streptococcus pyogenes
–– Children with increased risk of beta-lactam
(group A Streptococcus) are the most com-
resistance
mon causes.
–– Beta-lactam use within the past 30 days
• Viral: respiratory syncytial virus (RSV),
–– Concomitant purulent conjunctivitis (likely
picornavirus, coronavirus, influenza,
H. influenzae)
adenovirus
–– Recurrent AOM unresponsive to amoxicillin
Clinical Presentation • For patients with hypersensitivity to penicillin:
• Fever, irritability, apathy, anorexia, vomiting, –– Macrolides
diarrhea, otalgia, otorrhea, hearing loss –– Cefdinir, cefuroxime, ceftriaxone
• Frequent nighttime awakening
Complications
Diagnosis • Intratemporal: conductive hearing loss
• Pneumatic otoscopy showing decreased tym- (CHL), tympanic membrane perforation,
panic membrane mobility remains the best ossicular erosion, labyrinthitis, facial nerve
method for diagnosing the presence of middle paralysis, mastoiditis, subperiosteal abscess,
ear fluid petrous apicitis, sigmoid sinus thrombosis
• Intracranial: meningitis, epidural/subdural/ 6 months, avoidance of tobacco smoke

parenchymal abscess, cavernous sinus throm- exposure
bosis, otitic hydrocephalus • Prophylactic antibiotics are not
recommended
Recurrent Acute Otitis Media Suggested Follow-Up

• < 2 years of age: 8–12 weeks after diagnosis/
• 3 episodes in 6 months or 4 episodes in 1 year treatment of AOM
with 1 episode in the preceding 6 months [3] • < 2 years of age with language or develop-
• Associated conditions overlap with risk fac- mental delay: 8–12 weeks after diagnosis/
tors for Eustachian tube dysfunction: age treatment of AOM
< 2 years, allergic rhinitis/sinusitis, mucocili- • > 2 years of age with no comorbidities/lan-
ary dysfunction, craniofacial abnormalities, guage or development delay: next routine
immunodeficiency. visit
• Hallmark on physical exam is tympanoscle-
rosis (a.k.a. myringosclerosis): white plaques
on the tympanic membrane, which represent O titis Media with Effusion (OME)
a form of scarring (Fig. 18.2)
• Recommendations to decrease risk: pneumo- • Middle ear effusion without signs of acute
coccal conjugate vaccine, annual influenza infection
vaccine, exclusive breastfeeding for at least
Etiology
• After AOM (typically):
–– In the presence of Eustachian tube dys-
function in the absence of AOM
• It is estimated up to 90% of OME will resolve
spontaneously within 3 months.
• 30% to 40% of patients will have recurrent
episodes of OME.
• Most common cause of pediatric hearing loss.
• Frequency decreases as children age.
• More common in patients with Eustachian
tube dysfunction:
–– Craniofacial abnormalities (cleft palate
and others): weak Eustachian tubes sec-
ondary to palate abnormalities
–– Mucociliary dysfunction: primary ciliary
dyskinesia
–– Concurrent blockage of the Eustachian
tube opening: adenoidal hypertrophy, aller-
gic rhinitis/sinusitis
Investigations
• Hearing evaluation:
Fig. 18.2 Right tympanic membrane demonstrating –– Children with OME > 3 months
tympanosclerosis
–– Children at risk of speech, language, and –– Refer to otolaryngology if debridement is

learning delay required.
• Speech language evaluation: • Topical antimicrobials/corticosteroids (must
–– In children at risk of speech, language, and cover Pseudomonas and methicillin-resistant
learning delay Staphylococcus aureus [MRSA]):
• If topical antibiotics failed, consider systemic
Treatment antibiotics (broad spectrum covering
• Observation, “watchful waiting” Pseudomonas and MRSA)
–– In children with OME with low risk of
speech, language, and learning delays with
speech awareness thresholds showing hear- Indication for Myringotomy
ing loss less than 20 dBs. and Tympanostomy Tubes for Acute
–– Monitor every 3 months to ensure resolu- Otitis Media (AOM) and Otitis Media
tion of effusion
with Effusion (OME) [4, 5]
• Myringotomy and tympanostomy tube
insertion • Bilateral myringotomy and tympanostomy
–– See Indication for Myringotomy and tubes are indicated for a patient with the
Tympanostomy Tubes for Acute Otitis following:
Media (AOM) and Otitis Media with –– Bilateral OME for 3 months or more and
Effusion (OME) documented hearing difficulties
–– Unilateral or bilateral OME for 3 months
hronic Suppurative Otitis Media
C and symptoms likely related to OME, for
example, vestibular symptoms, poor school
(CSOM)
performance, behavioral difficulties, ear
Definition discomfort, and decreased quality of life
• Otorrhea (> 6 weeks or recurrent) from a –– Recurrent AOM and unilateral or bilateral
middle ear and/or mastoid infection in the middle ear effusion at the time of assessment
presence of tympanic membrane perforation –– At-risk children (such as those having cra-
(or ventilation tube) niofacial abnormalities or having only one
hearing ear), with unilateral or bilateral
Common Pathogen OME that is unlikely to resolve quickly as
• Mixed infections: reflected by a type B tympanogram (flat) or
–– Gram-negative bacilli (Pseudomonas, persistent effusion for 3 months or longer
Klebsiella, Proteus, Escherichia coli) • Complications of Tympanostomy Tubes
–– Staphylococcus aureus –– Tube otorrhea (most common)
–– Anaerobes –– Blockage of the tube
–– Granulation tissue formation
Clinical Presentation –– Displacement of the tube in the middle ear
• Otorrhea, TM perforation, inflamed middle –– Tympanic membrane changes: myringo-
ear mucosa, conductive hearing loss sclerosis, atrophy, atelectasis, retraction
Treatment pocket
• Keep the ear clean and dry: –– Persistent tympanic membrane perforation
–– Water precautions (avoid getting water in (may require surgical repair)
ear) –– Anesthesia-related complications
Acute Mastoiditis Types

• Congenital
Background –– Presents as a white mass, most often in the
• Suppurative infection of the middle ear (acute anterior-superior middle ear space with an
otitis media) that spreads to the mastoid cav- intact tympanic membrane
ity, resulting in osteitis of the mastoid bone • Acquired
• May become purulent and lead to bony break- –– Squamous epithelium which enters the
down within the mastoid bone (acute coales- middle ear via the retraction pocket (invag-
cent mastoiditis) ination), migration through tympanic
membrane perforation, or iatrogenic
Common Presentation implantation
• Erythema, tenderness, and edema over the
mastoid bone (postauricular region) Clinical Presentation
• Protuberant ear • Conductive hearing loss
• Fever, adenopathy, otitis media • Persistent otorrhea
• Tympanic membrane retraction pocket filled
Assessment with squamous epithelial debris/crusts
• Complete blood count (CBC), inflammatory • Possible whitish mass behind the TM (not
markers, audiometric evaluation always seen)
• Imaging: computed tomography (CT) of the
temporal bones (look for bony breakdown Complications
within the mastoid suggestive of • Erosion/destruction of the ossicular chain,
coalescence) chronic otitis media, labyrinthine fistula,
–– If there’s any concern for intracranial com- intracranial complications/abscess, facial
plication, use of contrast is recommended. nerve paralysis
Treatment Treatment
• Immediate otolaryngology consultation • Otolaryngology consultation is mandatory.
• Systemic antibiotics (usually requires intra- • Requires surgery (tympanomastoidectomy,
venous antibiotics) possible ossicular chain reconstruction)
• Possible myringotomy (tympanocentesis/cul- • Long-term follow-up required by
ture) and ventilation tube (use topical antimi- otolaryngology
crobial if the tube is present)
• Cortical mastoidectomy for cortical erosion
of the mastoid or intracranial complications Labyrinthitis
• Extremely rare in children
Cholesteatoma • Bacterial or viral invasion into the inner ear/
cochlear labyrinth; may be associated with
Definition permanent hearing loss, vestibular dysfunc-
• Squamous epithelium in the middle ear and tion, or meningitis
mastoid cavities (misnomer as there’s no
cholesterol) Clinical Presentation
• Risk of leading to recurrent infections, as • Vertigo, hearing loss, tinnitus, possible mid-
well as bone and soft tissue erosion dle ear infection:
–– Labyrinthitis causes vertigo and hearing Physical Exam

loss, whereas vestibular neuritis causes • Vital signs
vertigo but spares hearing. • Head and neck: complete exam, inspection of
the middle ear/TM, pneumatic otoscopy
Diagnosis • Neurologic: complete cranial nerve exam,
• Clinical presentation, often preceded by an extraocular movements/nystagmus, coordi-
upper respiratory infection (URI) nation (finger-to-nose testing), gait,
• Obtain an urgent audiogram (sensorineural Romberg’s test, gross vision testing
hearing loss) • Audiometric evaluation
Treatment Treatment
• Treat underlying infectious process: • Varies based on etiology.
–– Bacterial (S. pneumoniae, H. influenzae, • Refer to an otolaryngologist if suspicious of
M. catarrhalis): systemic antibiotics peripheral cause of vertigo; consider neurol-
–– Viral (cytomegalovirus [CMV], mumps, ogy referral if suspicious of central cause of
varicella-
zoster virus, rubeola, influenza, vertigo
parainfluenza, etc.): bed rest and hydration
–– +/− Myringotomy/ventilation tube if acute
otitis media is present Benign Paroxysmal Vertigo
of Childhood
Vertigo Definition
• Most common peripheral vestibular disorder,
Definition typically self-limiting, can be recurrent
• Illusion of rotational, linear, or tilting move- • Distinctly different from benign paroxysmal
ment (i.e., “spinning,” “turning”) of the positional vertigo (BPPV), which is common
patient or their surroundings in adults but not in children
Types of Vertigo Causes
• Central/systemic: • Spontaneous, posttraumatic, post-viral
–– Vascular (i.e., migraines, autoimmune dis- • Thought to be a migraine equivalent
orders, stroke); anemia; brain tumor; medi-
cations, toxin, and chemotherapy; Clinical Presentation
neurologic disorders (i.e., seizures, multiple • Brief recurrent episodes of vertigo lasting
sclerosis); metabolic disorders (i.e., thyroid seconds to less than 1 min
disease, diabetes); anxiety and panic attack • Can be pale and sweaty, vomits during an epi-
• Peripheral (related to the ear): sode and then appears back to normal
–– Benign positional vertigo of childhood • No hearing loss or tinnitus
(most common), vestibular neuritis due to
viral infections (Epstein-Barr virus [EBV] Diagnosis
most common), perilymph fistula (abnor- • Clinical history essential; physical exam and
mal connection between the inner ear and vestibular testing usually normal:
middle ear), trauma to the vestibular sys- –– Rule out other more sinister causes of ver-
tem/concussion, Ménière disease, cerebel- tigo as directed by history and exam.
lopontine angle tumors/acoustic neuroma – – Often a family history of migraines.
Treatment
• Usually self-limiting
• Counsel on risk of typical migraine head-
aches later in life
Meniere Disease
Background
• Rare in children, but the prevalence ranges
from 1.5% to 4% among children diagnosed
with vertigo
Clinical Presentation (Triad)

1. Episodic vertigo (minutes to hours) Fig. 18.3 Audiogram of mild conductive hearing loss
2. Episodic fluctuating sensorineural hearing

loss (typically unilateral)
3. Tinnitus +/− aural fullness in the affected ear
Diagnosis
• Clinical.
• Obtain an audiogram at time when patient
reports hearing loss.
Management
• Refer to an otolaryngologist if suspicious of
Meniere disease
HEARING LOSS
AND AUDIOLOGY
Fig. 18.4 Audiogram of moderate to moderate to severe
sensorineural hearing loss
Three Main Types of Hearing Loss
• Conductive hearing loss (CHL): neural hearing loss (e.g., damage to
–– Normal bone conduction threshold with cochlear, neural pathways and others)
abnormal air conduction thresholds –– No ABG (Fig. 18.4)
–– Presence of an air-bone gap (ABG) • Mixed hearing loss (CHL + SNHL):
–– Indicative of a middle ear issue, for exam- –– Presence of conductive hearing loss and
ple, abnormalities with the tympanic mem- sensorineural hearing loss at the same time
brane, ossicles, or middle ear space (i.e., (Fig. 18.5)
effusion; Fig. 18.3)
• Sensorineural hearing loss (SNHL):
–– When the air conduction is the same as the C ongenital Hearing Loss
bone conduction with both showing abnor-
• Congenital hearing loss can be divided into two
mal hearing thresholds, this is suggestive
main categories, environmental and genetic.
of an inner ear issue resulting in sensori-
This is further described in Table 18.1 [6]
• Stickler syndrome: SNHL, ocular abnormali-

ties (myopia, retinal detachment), Marfanoid
habitus, Pierre Robin sequence
• Branchio-oto-renal syndrome: mixed hearing
loss (sensorineural and conductive hearing
loss), pinna deformities, preauricular or neck
pits/fistulas/tags, kidney abnormalities
• Treacher Collins syndrome (mandibulofa-
cial dysostosis): CHL (malformed ossicles),
aural atresia/stenosis, zygomatic/mandibu-
lar hypoplasia
• Others: neurofibromatosis type II, Apert syn-
Fig. 18.5 Audiogram of mild to moderate sensorineural
drome (acrocephalosyndactyly), Crouzon
hearing loss with ~20 dBs conductive hearing loss syndrome (craniofacial dysostosis)
Table 18.1 Causes of congenital hearing loss [6] Autosomal Recessive (mnemonic “PUJ”)
50% Cytomegalovirus (CMV) • Usher syndrome:
environmental Neonatal icterus –– Leading cause of deafness and blindness
Meningitis –– SNHL, blindness (retinitis pigmentosa),
Rubella vestibular dysfunction
Prematurity
• Pendred syndrome: SNHL, goiter, enlarged
Ototoxicity
Other infections vestibular aqueducts
50% genetic 30% Autosomal recessive: • Jervell and Lange-Nielsen syndrome: SNHL,
syndromic Usher syndrome cardiac defects (prolonged QT), syncope,
Pendred syndrome sudden death
Jervell and Lange-
Nielsen syndrome
Alport syndrome
X-Linked
(sometimes X-linked) • Alport syndrome: X-linked, hearing loss, pro-
Autosomal dominant: gressive nephritis, occasional ocular lesions
Waardenburg syndrome
Stickler syndrome
Branchio-oto-renal
syndrome
Genetic Nonsyndromic Hearing Loss
Treacher Collins
syndrome Connexin Mutations
70% Connexin mutations • Most common cause of hereditary nonsyn-
nonsyndromic most common dromic hearing loss.
• Connexin 26 mutations (GJB2 gene) account
Genetic Syndromic Hearing Loss for ~80%
• Testing done as part of the workup for bilat-
• More than 500 syndromes are associated with eral SNHL.
hearing loss. The most common are listed as
follows: Universal Newborn Hearing Screening
• Implemented across all states in the USA and
Autosomal Dominant provinces in Canada.
• Waardenburg syndrome: SNHL, hyper- • Tests hearing with otoacoustic emission (OAE)
telorism, pigmentary abnormalities screening or with an automated auditory
b rainstem response (ABR) shortly after birth • Sound presented via speakers. Skilled exam-
(usually before the neonate leaves the iner observes for patient response (i.e., star-
hospital) tling or head turning toward sound)
• Any infant who fails the initial screen should • Grossly assessed auditory thresholds of “bet-
be referred to an audiologist for a full evalua- ter” ear (tests both ears at the same time)
tion no later than 3 months of age.
• For all children in whom hearing loss is estab- Visual Response Audiometry (VRA)
lished by full audiologic evaluation, interven- • Six months to 3 years of age.
tion must begin as soon as possible and no • Toddler encouraged to look for auditory stim-
later than 6 months of age ulus (i.e., lights, toys, motion for
reinforcement)
Clues to Hearing Loss in a Child Visit • Each ear may be tested individually—poten-
• Speech delay tial to provide complete audiogram
• Social and behavioral challenges
• A child asking people to repeat themselves, Play Audiometry
not hearing instructions • 3 to 5 years of age.
• Listening to loud television or music • Child performs tasks in response to auditory
• Clumsiness—may be a clue to middle ear stimulus (e.g., “Pick up a block and place it in
fluid the bucket when you hear the beep”)
• Each ear is tested individually, frequency
specific
Pediatric Audiometric Testing
Conventional Audiometry
Evoked Otoacoustic Emission (OAE) • 4 to 6 years of age and older
• OAE detects the sound coming from the • Child instructed to push a button or raise a
cochlea in response to clicks or tones. hand when a tone is heard
• OAE affected by external or middle ear debris • Complete audiogram, ear specific, frequency
(high false-positive rate) specific
• Used for all ages
• No infant cooperation is required. Hearing Loss Classification
• Classified by hearing threshold levels (may
Auditory Brainstem Response (ABR) vary slightly based on sources):
• ABR measures the electroencephalographic –– Normal: < 19 dB
waveform response from the vestibuloco- –– Mild: 20–40 dB
chlear nerve to higher central nervous system –– Moderate: 41–55 dB
auditory centers. –– Moderate to severe: 56–70 dB
• ABR minimally affected by external or mid- –– Severe: 71–90 dB
dle ear debris. –– Profound: 91 dB
• Can be used at any age. Tympanometry
• Patient must be asleep or very still—may • Age: all ages except newborn.
require sedation. • Detects the mobility of TM and external audi-
• Often used to confirm abnormal OAE results. tory canal volumes.
• Normal canal volumes range between 0.2 and
Testing Methods 1.5 ml:
–– Type A
Behavioral Observation Audiometry (BOA) ◦◦ Normal peak between − 150 and + 50
• Birth—6 months of age deka pascals
–– Type B
◦◦ Flat, no peak
◦◦ Suggestive of:
▪▪ Middle ear effusion (normal to low
volumes)
▪▪ Tympanic membrane perforation
(high canal volumes)
▪▪ Patent ventilation tube (high canal
volumes)
–– Type C
◦◦ Peak negatively shifted (< −150)
◦◦ Suggestive of a retracted tympanic mem-
brane or Eustachian tube dysfunction
Patterns of Hearing Loss Fig. 18.6 Audiogram of tympanic membrane perforation
Interpreting an Audiogram
• Y-axis = hearing level in decibels (dBs) or the
“loudness” of sound
• X-axis = frequency of sound presented mea-
sured in Hertz (low pitch to high pitch)
• “x” = responses from the left air conduction
line
• “>” = responses from the left bone conduc-
tion line
• ABG = difference between air conduction
and bone conduction lines
Common Clinical Scenarios

• Tympanic membrane perforation (Fig. 18.6):
–– Audiometric findings:
◦◦ ABG Fig. 18.7 Audiogram of middle ear effusion
◦◦ Flat tympanogram
◦◦ High canal volumes
◦◦ Mild conductive hearing loss
• Middle ear effusion (Fig. 18.7):
–– Audiometric findings:
◦◦ ABG
◦◦ Flat tympanogram
◦◦ Low or normal canal volumes
◦◦ Mild conductive hearing loss
• Ototoxicity (Fig. 18.8):
–– Ototoxic medications cause hearing loss
by damaging the hair cells within the
cochlea, resulting in sensorineural hearing
loss, primarily in the high frequencies.
Fig. 18.8 Audiogram of ototoxicity
• Wide variety available, depending on hearing

needs and preferences.
• Fitting and programming processes are com-
plex and completed by an audiologist
Bone-Anchored Hearing Aid (Osseo-integrated

Auditory Implant)
• Titanium implant surgically placed in mas-
toid bone behind the ear.
• Sound processor is placed externally on the
implant and conducts sounds via bone con-
tact and vibration.
• Primarily used in patients with unilateral or
Fig. 18.9 Audiogram of hereditary hearing loss bilateral CHL with congenital ear malforma-
tion (i.e., atresia, canal stenosis)
–– Most commonly caused by cisplatin/
carboplatin. Cochlear Implants
–– Audiometric findings: • Convert sound to an electrical signal that
◦◦ High-frequency sensorineural hearing stimulates the cochlear nerve.
loss (moderate to moderate to severe) • External component captures sound and con-
◦◦ No ABG verts it to an electrical signal.
◦◦ Normal tympanogram and volumes • Internal component delivers frequency-
(typically) specific electrical signal to the cochlear
• Hereditary hearing loss (Fig. 18.9): nerve
–– Cookie bite (U-shape) pattern of sensori- • Multiple cochlear implant devices are avail-
neural hearing loss able, depending on hearing loss pattern and
–– No ABG, normal tympanogram, normal patient preferences
canal volumes • Cochlear implant criteria are very specific
and include a multidisciplinary team (otolar-
Sound Amplification Devices yngologist, speech pathologist, audiologist,
• Early identification and intervention is social worker, psychologist, etc.)
required to maximize hearing and speech • In general, indicated for children (US Food
development, as well as to achieve develop- and Drug Administration [FDA] approved for
mental milestones. 12 months of age or older, though children
• Refer to an otolaryngologist when an abnor- are often implanted younger than 12 months
mal hearing screen is identified. of age) with pre- or postlingual severe to pro-
• Hearing interventions are dependent on type found bilateral high-frequency SNHL
and severity of hearing loss. • Fitting and programming is a complex pro-
cess performed by a specialized cochlear
Hearing Aids
implant audiologist and requires multiple
• Non-implantable external hearing device that
audiology visits
amplifies frequency-specific sounds.
• There is increasing evidence regarding the
• Used for unilateral or bilateral CHL, SNHL,
benefits of binaural hearing
and mixed hearing losses.
NOSE AND NASOPHARYNX • Unilateral:

–– Identified at birth due to inability to pass
Choanal Atresia 6F catheter or later in childhood with uni-
lateral symptoms of rhinorrhea, decreased
Background nasal patency, or stertor
• Congenital obstruction of the choana (poste- –– Surgical repair based on symptoms and
rior nasal aperture—connects the nasal cavity growth, often around 1 year of age and
to the nasopharynx): nearly all before 4 years of age
–– Diagnosis is suspected with the inability to
pass a 5F suction catheter through the nose E pistaxis
into the nasopharynx
• It may be mixed (60%), bony (30%), or mem- Background
branous (10%) (CT scan can help to confirm • In children, 90% of epistaxis occurs from the
and identify the type of atresia) anterior septum (Kiesselbach plexus)
• Unilateral or bilateral 2:1 ratio. • Posterior epistaxis is rare in children and
• Syndromic association with congenital anom- should prompt further evaluation.
alies is associated with unilateral choanal • Most common causes: trauma (i.e., nose pick-
atresia 50% of the time, and there is a syn- ing), mucosal irritation and drying, foreign
dromic association 75% of the time if the body, and medications (e.g., nasal steroids)
atresia is bilateral: Other Causes
–– Can be associated with syndromes (e.g., • Tumors, e.g., juvenile nasopharyngeal angio-
coloboma of the eye, heart defects, atresia fibroma (occurs in pubescent males), pyo-
of the nasal choanae, retardation of growth genic granuloma
and/or development, genital and/or urinary • Vascular malformation: hemangioma, telan-
abnormalities, and ear abnormalities giectasia, Osler-Weber-Rendu syndrome
(CHARGE) and deafness, trisomy 21, tri- (+ family history)
somy 18, Treacher Collins syndrome, • Bleeding diathesis: von Willebrand disease,
Apert syndrome, Crouzon syndrome, velo- leukemia, liver disease
cardiofacial syndrome)
Management
Clinical Presentation • Usually self-limiting with application of con-
• Bilateral: stant pressure for 5 min by squeezing the
–– Severe respiratory distress at birth, cyclical sides of the nose shut
cyanosis—pink with crying, cyanotic when • Discourage nose picking/rubbing.
not crying • Avoid mucosal dryness—humidifier in the
–– Requires immediate oral airway or intuba- bedroom; apply small amount of nasal lubri-
tion; refer to otolaryngology once airway is cant to the anterior septum
secured for surgical repair in the first few • If severe, it will need IV access and formal
days of life nasal packing +/− airway management +/−
–– Patients with bilateral atresia and those hemodynamic resuscitation
with syndromes (e.g., CHARGE) are at • Refer to an otolaryngologist if suspicious for
greater risk of restenosis a foreign body, tumor, recurrent epistaxis, or
severe epistaxis
Nasal Trauma Table 18.2 Clinical characteristics of viral vs. bacterial

rhinosinusitis
Background Clinical Bacterial
• Nasal fractures are the most common facial feature Viral rhinosinusitis rhinosinusitis
Fever Absent or occurs Present, > 39 °C
fracture in children (followed by the
early (first 24 h)— (102 °F) × 3 days, may
mandible) low grade, resolves develop or recur on
• Most commonly secondary to falls, sporting in 2 days days 6–7 of illness
collisions, motor vehicle accidents. Nasal Peaks on days 3–6 Fails to improve or
discharge and then improves worsens
Presentation Cough Peaks on days 3–6 Fails to improve or
and then improves worsens
• External nasal deformity, nasal obstruction, Ill- Absent If severe or
epistaxis, anosmia, septal deviation, edema, appearance complicated
bruising Severe Absent If severe or
headache complicated
Assessment Clinical Peaks on days 3–6 > 10 days, without
• Pediatric Advanced Life Support (PALS); rule course and then improves improvement
out injuries to the cervical spine, central ner-
vous system, and chest, orbit/vision problems, • Acute bacterial rhinosinusitis (ABRS): sinus-
midface stability, malocclusion, presence of itis secondary to bacterial infection
telecanthus, cerebrospinal fluid leak, etc. • Acute: < 90 days
• Nasal x-rays not useful.
Risk Factors
• Must evaluate for septal hematoma/abscess.
• URI
Clinical Presentation • Daycare
• Boggy asymmetrical swelling of the nasal • Allergic rhinitis
septum not responsive to topical • Anatomic anomalies (e.g., septal deviation)
vasoconstriction
Presentation
• Management of nasal hematoma: requires
• Congestion, purulent rhinorrhea, tenderness
urgent drainage by an otolaryngologist +/−
over sinuses:
bolster dressing to prevent nasal cartilage
–– Clinical presentation may be variable based
necrosis
on the pathogen, as described in Table 18.2.
Management • Virology/microbiology:
• If there’s cosmetic deformity +/− functional –– Viruses: rhinovirus, parainfluenza, influ-
issues (e.g., decreased nasal patency), refer to enza, adenovirus
otolaryngology for reduction of nasal –– Bacteria: S. pneumoniae, H. influenzae, M.
fracture. catarrhalis
–– Risk of antimicrobial resistance [7]:
◦◦ Age < 2 years, daycare antibiotics in the
past month, hospitalization within
SINUSES
5 days
Acute Rhinosinusitis Treatment
• Over-the-counter cold medications or decon-
Definitions
gestants (either systemic or intranasal) are
• Sinusitis: mucosal inflammation of paranasal
not recommended for children under 12 years
sinuses typically caused by a viral illness
of age.
• Supportive therapies: hydration, saline nasal Risk Factors

rinses, acetaminophen/ibuprofen. • Young age (developing immune system),
URI, ciliary dysfunction, allergic rhinitis,
Treatment of ABRS [8] gastroesophageal reflux disease (GERD),
• Saline nasal rinses. immune deficiency, cystic fibrosis
• Antibiotics:
–– First line: amoxicillin/clavulanic acid Microbiology
45 mg/kg divided BID × 10–14 days • Aerobes: S. pneumoniae, M. catarrhalis, H.
–– If at risk of resistance (see above), 90 mg/ influenzae, Staphylococcus aureus,
kg divided BID × 10–14 days Pseudomonas
–– Third-generation cephalosporins if there’s • Anaerobes: Peptococcus, Peptostreptococcus,
penicillin hypersensitivity Bacteroides
• Surgery:
–– No role in ABRS, unless there’s evidence of Diagnosis
complication (i.e., orbital or intracranial) • Clinical diagnosis (imaging not required for
• Monitor for complications: diagnosis)
–– Orbital • Plain X-ray films are generally NOT helpful.
–– Preseptal cellulitis, orbital cellulitis, sub- • CT scan indicated when failed medical man-
periosteal abscess, orbital abscess, cavern- agement and surgical intervention is being
ous sinus thrombosis considered.
–– Intracranial
–– Meningitis, epidural abscess, subdural Treatment
abscess, parenchymal abscess, etc. • Medical management:
–– Osteomyelitis (typically of frontal bones) –– Saline nasal rinses.
–– Antibiotics: amoxicillin-clavulanic acid
Imaging × 3–4 weeks.
• CT scan of the sinuses is only indicated for – – Topical nasal steroids.
the following: –– Consider treatment of gastroesophageal
–– If suspicious for sinusitis complications reflux disease (GERD) if suspicious.
(e.g., orbital or intracranial) • Surgical:
–– Failure of antibiotic treatment × 48 h –– Only considered if there’s failure of long-
–– Immunocompromised patient term medical management.
• Findings: opacification of sinuses, mucosal –– Adenoidectomy is first line of surgery.
thickening, air-fluid levels –– If symptoms are persistent following ade-
–– Note: These findings are also present with noidectomy and the patient continues to fail
the common cold. medical management, functional endo-
scopic sinus surgery (maxillary antrostomy
and ethmoidectomy usually sufficient unless
Chronic Sinusitis clinical symptoms or imaging suggests
other sinuses involved) may be considered.
Definition • Ancillary tests:
• Persistence of symptoms > 12 weeks. –– If medical management fails, consider
• Symptoms include nasal congestion, facial allergy testing if suspicious for allergies.
pressure, nasal obstruction, rhinorrhea/post- –– If negative, consider workup for primary
nasal drip, and altered sense of smell. immunodeficiency disorder if suspicious.
Frontal Sinus Trauma exudative tonsils, tender lymphadenopa-

thy; rarely seen with cough or rhinorrhea;
• Rare in children, as frontal sinuses begin most common in children 5–12 years of
forming around 6–7 years of age. age.
• Associated with high-impact injury—must –– GABHS pharyngitis should be treated to
rule out cervical spine injuries and intracra- reduce the risk of rheumatic fever and scar-
nial injury. let fever.
• May present with forehead lacerations or –– Other bacterial causes: syphilis, pertussis,
swelling, palpable frontal defect, pain, epi- gonorrhea, diphtheria, Fusobacterium.
staxis, cerebrospinal fluid leak. –– Untreated Fusobacterium infections may
• CT scan optimal for identifying fractures, lead to Lemierre syndrome: thrombus of
magnetic resonance imaging (MRI) consid- the internal jugular vein with potential for
ered in addition to assessing intracranial septic emboli.
involvement.
• If frontal sinus fracture is present, consult Symptoms
otolaryngology for further management. • Sore throat, pain with swallowing, ear pain
• Conservative or surgical depending on frac- (referred), malaise, fever, oropharyngeal ery-
ture pattern. thema, cervical lymphadenopathy
• If suspicious for intracranial involvement,
consult neurosurgery. Diagnosis
• Based on history and physical exam
• Throat cultures, the diagnostic standard:
–– A positive posttreatment culture represents
THROAT AND OROPHARYNX the asymptomatic chronic carrier state (not
a significant source for the spread of
Tonsillitis/Pharyngitis GABHS, no treatment needed)
–– If there are recurrent symptoms and
Etiology persistently positive culture, consider
• Infectious (most common), allergy, GERD compliance failure, exposure, immunosup-
[9] pression, and penicillin-resistant organ-
• Viral (most common): ism (consider second-line therapy, such as
–– Rhinovirus, coronavirus, adenovirus, her amoxicillin-clavulanate)
pes simplex virus (HSV), EBV, coxsackie • GABHS rapid antigen test:
virus –– Sensitivity/specificity: enzyme immunoas-
–– Usually associated with symptoms of say in children, pooled sensitivity esti-
cough, sneezing, rhinorrhea, low-grade mated at 86% and the pooled specificity
fever estimated to be 92%; for immunochro-
• Bacterial (streptococci, pneumococci, H. matographic assay in children, pooled sen-
influenzae): sitivity estimated at 88% and the pooled
–– Bacteria are responsible for 5–10% of specificity estimated to be 86%
pharyngitis. –– Throat culture should follow negative rapid
–– Group A b-hemolytic Streptococcus antigen test when diagnosis of GABHS
(GABHS)—most common bacterial cause infection is strongly suspected.
[10] • Monospot test (EBV)
–– Usually associated with symptoms of high- • Streptococcal antibody titers not
grade fever, tonsillar/palatal petechiae, recommended
Treatment Table 18.3 Clinical features of peritonsillar abscess vs. ret-

• Ensure airway safety. ropharyngeal space abscess
• Supportive: Retropharyngeal abscess Peritonsillar abscess
–– Hydration, humidity, analgesia < 6 years old Adolescent
Fever, throat pain, neck stiffness Fever, throat pain,
• Antibiotics if bacterial infection is suspected
trismus
(confirm with cultures): Purulence of retropharyngeal Purulence of tonsillar
–– Treatment proposed to decrease symptoms lymph node fossa
within ~16 h, decreased rates of peritonsil- May need imaging studies Usually diagnosed
lar abscess (PTA) and retropharyngeal clinically
abscess.
–– Modified Centor score may be used to help • Clinical features of PTA and retropharyngeal
physicians decide which patients need no space abscess are outlined in Table 18.3.
testing, throat culture/rapid antigen detec- • PTA and retropharyngeal abscess can occur
tion testing, or empiric antibiotics. concurrently.
Management
Peritonsillar Abscess (PTA) • Surgical incision and drainage.
• Antibiotic therapy (penicillin or
Definition clindamycin)
• Peritonsillar space defined: • Two or more PTAs may require a future ton-
–– Space between the palatine tonsil, superior sillectomy (bilateral) once infection resolves.
constrictors, and tonsillar pillars • “Quinsy tonsillectomy”—tonsillectomy at
the time of infection may be considered in
Etiology younger children but is rare in practice sec-
• More common in adolescents ondary to acute inflammation of the tonsils.
• Spread of infection from the tonsil
• Pathogens: aerobes (Streptococcus pyogenes,
Staphylococcus aureus, Haemophilus influ- Retropharyngeal Abscess
enzae, and Neisseria species) and anaerobes
Definition
Clinical Presentation • Space between pharyngeal constrictors and the
• Sore throat, painful swallowing, uvular devi- alar fascia (skull base to the mediastinum)
ation to the contralateral side (medialization),
trismus, asymmetrical swelling on the soft Etiology
palate, “hot potato” voice, fevers, referred • Presents most commonly in children
otalgia. • Spread of infection from the tonsils, sinuses,
• Symptoms are typically present for at least and/or nasopharynx
3 days before abscess is formed; double wors- • Polymicrobial flora (most commonly
ening phenomenon is common. Staphylococcus aureus, Streptococcus spe-
cies, and anaerobes)
Diagnosis
• History and physical examination. Clinical Presentation
• CT for atypical cases or if there are concerns • Fevers, “hot potato voice,” painful swallow-
for retropharyngeal/parapharyngeal space ing, drooling, decreased neck range of motion
involvement. (typically limited neck extension), trismus
Indication for Tonsillectomy
(+/– Adenoidectomy) [11, 12]
Absolute Indications
• Moderate to severe obstructive sleep apnea
• Suspicions of tonsillar malignancy, including
posttransplant lymphoid proliferative disor-
der (PTLD)
Relative Indications
• Mild obstructive sleep apnea
• Recurrent tonsillitis—must meet criteria:
–– Frequency:
◦◦ Seven or more episodes in 1 year
◦◦ Five or more episodes per year for
2 years
◦◦ Three or more episodes per year for
3 years
• Associated with one or more of the
Fig. 18.10 Concurrent peritonsillar abscess on the right and
retropharyngeal abscess in a 10-year-old boy as seen on axial
following:
computed tomography scan –– Temperature > 38.3 ° C (101 °F)
–– Cervical lymphadenopathy
possible if there’s pterygoid inflammation, –– Tonsillar exudate
possible airway compromise/stridor if severe –– Positive test for GABHS
• Chronic tonsillitis unresponsive to antimicro-
Diagnosis bial therapy
• Lateral neck radiograph: abnormally • Severe halitosis
increased thickness of the prevertebral soft • PTA (greater than one episode)
tissue (greater than half thickness of the adja- • PFAPA syndrome (periodic fever, aphthous
cent vertebral body) ulcers, pharyngitis, cervical adenitis)
• CT scan with contrast useful for localization, • PANS/PANDAS syndrome: a controversial
extension, phlegmon, or abscess (Fig. 18.10) indication (pediatric acute-onset neuropsy-
chiatric syndrome/pediatric autoimmune
Treatment neuropsychiatric disorders associated with
• Airway management if required and/or ongo- streptococcal infection)
ing airway monitoring
• Hydration and analgesia Indication for Adenoidectomy Alone
• Antibiotics (may consider third-generation • Moderate to severe nasal obstruction with
cephalosporin, clindamycin, or ampicillin/ persistent symptoms
sulbactam for first line) • Refractory chronic sinusitis
• Surgical drainage indicated for failed medical • Recurrent acute otitis media or otitis media
management, well-defined rim-enhancing with effusion in a child who had prior tym-
abscess, systemic illness, and/or airway panostomy tubes that have now extruded
compromise (e.g., repeat surgery when indicated would
consist of adenoidectomy plus myringotomy or hypoventilation (CO2 > 50 mmHg for
± insertion of ventilation tube) and is over > 25% total sleep time) as determined on
4 years of age polysomnogram (PSG)
Postsurgical Complications of Adenotonsillectomy Etiology

• Anesthesia related • OSA syndrome affects 2–10% of children;
• Pain: moderate to severe lasting 7–14 days, adenotonsillar hypertrophy as a primary
requiring analgesia driver of OSA is most common between ages
• Hemorrhage: 2 and 6 years of age.
–– Bimodal timing
–– < 24 h postoperative: ~< 2% Clinical Presentation
–– 5 to 7 days postoperative (sloughing of • Nocturnal—snoring, mouth breathing, pauses
eschar): ~3% in breathing, enuresis, gasping or choking,
• Dehydration secondary to decreased oral restless/awakenings:
intake –– Children may still have OSA without
• Halitosis (expected) snoring.
• Immediate postoperative airway obstruction • Daytime: inappropriate sleepiness, inatten-
(due to anesthesia, analgesia, or sleep apnea) tion/learning problems, hyperactivity/aggres-
• Persistence of obstructive sleep apnea sion, irritability.
• Velopharyngeal insufficiency (VPI): • Children with OSA during infancy are more
–– New onset or worsening of existing VPI. likely to have a risk factor other than adeno-
–– High-risk patients: cleft palate, submucous tonsillar hypertrophy or obesity, such as cra-
cleft palate, impaired baseline palatal niofacial abnormality, neurologic problems,
movement (e.g., neurogenic), very large and genetic syndrome.
adenoid pad, velocardiofacial syndrome.
Risk is decreased by conservative approach Diagnosis
to surgery. • The American Academy of Pediatrics recom-
mends screening by history (snoring, daytime
symptoms) during well-child checks.
Obstructive Sleep Apnea (OSA) • Focused sleep history.
Syndrome • Physical exam—vitals including blood pres-
sure; craniofacial, oral, nasal, and oropharyn-
Definition geal exams; growth curve; and BMI should
• Sleep-disordered breathing (SDB): a patho- be recorded:
physiologic continuum that includes snoring, –– Adenotonsillar hypertrophy and obesity
upper airway resistance syndrome, obstruc- are the major causes in otherwise healthy
tive hypopnea syndrome, and OSA. children.
• OSA: episodes of complete or partial upper –– Usually there is evidence of large tonsils,
airway obstruction during sleep, often result- but small tonsils may cause symptoms dur-
ing in gas exchange abnormalities and arousing sleep; adenoids are best visualized by
als. True OSA results in detrimental clinical nasal endoscopy.
sequelae such as failure to thrive, behavior –– Strongest risk factor for OSA in adoles-
problems, learning problems, and cardiovas- cence is obesity.
cular disease. –– If there’s normal weight and small tonsils/
• Criteria for OSA: clinically relevant symp- adenoids, otolaryngology will look for
toms and an apnea hypopnea index (AHI) > 1 more rare causes of obstruction such as
laryngeal masses, lingual tonsillar hyper- MOUTH AND ORAL CAVITY

trophy, macroglossia, abnormal pharyn-
geal tone, and nasoseptal obstruction. phthous Ulcers
A
• PSG—gold standard for definitive diagnosis
(also requires presence of clinical symptoms) • Aphthous ulcer is the most common oral
and can help to inform treatment decisions ulcer.
and counsel caregivers:
–– If there’s clinical suspicion without high- Etiology
risk features (see below), offer PSG rather • Idiopathic (most common); other causes
than referral (otolaryngology, pulmonol- include immune disorders, infections, hor-
ogy, sleep medicine physician) monal cause, stress, trauma, and nutrition.
–– If there are high-risk features, PSG in a • Painful white ulcers on keratinized gingiva
facility experienced with children and surrounded by erythematous border.
referral are recommended:
◦◦ Obesity, craniofacial abnormalities, Types
mucopolysaccharidoses, Prader-Willi • Minor: most common, < 1 cm in diameter,
syndrome, sickle cell disease, Down painful, burning/tingling prodrome
syndrome, neuromuscular disorders, • Major: more painful, 1–3 cm in diameter, 1 to
congenital hypoventilation syndrome, 10 ulcers at one time, scarring potential
etc. • Herpetiform: multiple small ulcers (1–3 mm
• Classification based on AHI: mild OSA in diameter)
(1–4.9), moderate OSA (5–9.9), severe • Sutton’s disease: recurrent aphthous ulcers
(greater than 10) (major type)
Treatment Treatment
• Tonsillectomy and adenoidectomy—other- • Observation (self-limiting course)
wise healthy children with OSA and adeno- • May also consider analgesia, anti-inflamma-
tonsillar hypertrophy: tories, antibiotics if superinfected, and
–– Consideration of clinical symptoms, OSA antivirals
severity, comorbidities.
–– Obese children may experience weight
gain after surgery. Bifid Uvula
• Supportive care with watchful waiting—mild
• 2% of population (up to 10% in some ethnic
OSA, mild symptoms, and reevaluation in
groups)
6 months:
• Clinical presentation ranges from split to
–– Data based on Childhood Adenotonsillec-
duplication.
tomy Trial (CHAT) [13]
• May be a marker of submucous cleft palate:
• Positive airway pressure therapy: minimal
–– Lucency of the midline soft palate, palpa-
anatomic reason for obstruction, poor surgi-
ble notch of the midline hard palate
cal candidate, need to stabilize/optimize the
–– Associated with speech problems, VPI,
patient prior to surgery, persistent OSA after
dysphagia
tonsillectomy/adenoidectomy
• Rarely, may be associated with genetic
• Rapid maxillary expansion
syndromes:
–– Cornelia de Lange syndrome

–– Loeys-Dietz syndrome: increased risk of
aortic aneurysm
Cold Panniculitis
• Lobular, erythematous, acute eruption in adi-
pose tissue following exposure to cold and
subsequent inflammation.
• Cheeks and forehead often affected in infants.
• Differential: adiponecrosis subcutanea (sub-
cutaneous fat necrosis of the newborn, cold
panniculitis of the newborn), sclerema neona-
torum (often fatal, needle-shaped crystals),
post-steroid panniculitis, frostbite, and group
A streptococcal bacteremia.
• Diagnosis is clinical; biopsy if needed will
show lobular panniculitis with occasional
deposition of mucin.
• Treatment is symptomatic, with slow
rewarming.
Fig. 18.11 Mucocele of the lower lip

Ankyloglossia
• Abnormally short frenulum limiting effective • Can slowly grow in size
tongue mobility • Treatment: observation if not bothersome,
• In infants, if severe, may present with suck- surgical excision
ling difficulties and painful latch (if
breastfeeding)
• In older children, may result in speech articu- P
arotitis
lation issues, social mechanical issues (i.e.,
difficulty in licking an ice-cream cone, keep- Etiology
ing teeth clean, playing wind instruments, • Salivary stasis, obstruction (usually unilat-
“French” kissing) eral; stone, mass/tumor), retrograde bacterial
• Surgical intervention indicated for problem- migration, idiopathic
atic symptoms • Bacteria: Staphylococcus aureus (most com-
mon), Streptococcus viridans, H. influenzae,
Streptococcus pyogenes, E. coli
Mucocele • Viruses (usually bilateral): HIV, mumps,
influenza, coxsackie
• Painless, bluish submucosal lesion appearing • Recurrent parotitis of childhood:
on the lower lip (Fig. 18.11) –– Unknown etiology
• Typically secondary to trauma (i.e., biting –– Episodes occurring every 1–3 months
lower lip) –– May alternate sides
–– Typically resolves spontaneously • Cleft lips (+/− cleft palate) and isolated cleft
–– No antibiotic therapy needed unless there’s palate occur in distinct genetic lines.
presence of systemic symptoms • Higher prevalence in Asians and Native
Americans.
Symptoms • Cleft lip (CL): Males > females.
• Tender, red, warm parotid gland • Isolated cleft palate: Females > males.
• Purulence at Stensen’s duct with “milking” of
gland Risk Factors
• Teratogens (ethanol, thalidomide)
Diagnosis • Maternal diabetes
• History and physical exam • Amniotic band syndrome
• Cultures of purulent discharge to help guide
antibiotic therapy Genetic Evaluation
• 8% of isolated cleft palates are associated
Treatment with a syndrome.
• Conservative: rehydration, warm compresses, • Over 200 syndromes are associated with CL/
parotid massage, sialogogues. CLP, which most commonly include:
• Antibiotics (based on cultures) –– Stickler syndrome: CP, retinal detachment,
• If there’s no improvement with above treat- cataracts
ment, consider parotid imaging (CT or ultra- –– Treacher Collins syndrome: CP, midface
sound) for evaluation of abscess, stone, or hypoplasia, eyelid colobomas, ossicular
obstructing lesion. abnormalities
–– Apert syndrome: CP, acrocephaly, fused
digits, stapes fixation
Cleft Lip and Palate (CLP)
Feeding Difficulties
Epidemiology • Infants experience difficulty with “seal”—
• Second most common malformation (after often requires specialized nipple (i.e., Mead
clubfoot) Johnson crosscut, McGovern’s nipples)
• Cleft lip and palate (CLP): 1/1000 births. • Often require feeding in more upright posi-
• Cleft palate (CP): 1/2000 births (Fig. 18.12) tion with frequent rests and burping.
Otologic Disease
• Increased risk of developing Eustachian tube
dysfunction resulting in OME with CP/CLP
• Often requires myringotomy/ventilation tubes
Timing of Surgical Intervention

• CL generally is surgically repaired between
the ages of 10 and 12 weeks:
–– “Rule of tens”—10 pounds, 10 weeks old,
and hemoglobin of 10.0 g/dL (100.0 g/L)
• CP is usually repaired between 9 and
12 months of age.
For Follow-Up
• Difficulty in feeding and growth
Fig. 18.12 Young patient with cleft palate • Recurrent ear infections/possible hearing loss
• Dysfunctional speech and communication • Polymicrobial:

(i.e., velopharyngeal dysfunction) –– Streptococcus mutans (most common
• Dental problems cause of initial caries infection)
• Social struggles because of the child’s –– Alpha-hemolytic streptococci
appearance –– Anaerobes (Peptostreptococcus, Bacteroides,
Fusobacterium)
Robin Sequence (RS) Clinical Presentation

• Localized pain, edema, erythema, purulence
• Sequence defined as micrognathia, cleft pal- • Sensitivity to temperatures and palpation,
ate, and glossoptosis. loose tooth
• Occurs in isolation or with associated syn- • Orofacial swelling:
drome (i.e., trisomy 18 or Stickler –– Swelling below the jaw (mandibular
syndrome) abscess)
• Infants with RS are at high risk to develop –– Periorbital swelling (maxillary abscess)
respiratory distress and potentially have “dif-
ficult airways,” given their anatomy. These Imaging
infants require close airway monitoring in the • Evaluate airway compromise, gas-producing
postnatal period. organisms, presence of abscess, and extent of
• Management of respiratory distress in RS: involvement.
–– Prone positioning. • Panorex.
–– Place suture at the tip of the tongue and • CT scan.
pull the tongue forward.
–– Intubate if needed. If unable to intubate, Treatment
place a laryngeal mask airway. • Remove source of infection (i.e., tooth)
–– If patient fails extubation, patient may • Analgesia.
require: • Antibiotics.
◦◦ Mandibular distraction • Incision and drainage if an abscess is present.
◦◦ Tracheostomy
Delayed Dental Eruption arly Childhood Caries

E
• Normal range for dental eruption is between
8 and 18 months. Definition
• Delayed dental eruption is considered when • Caries affecting the primary dentition, espe-
teeth fail to erupt within 12 months of “nor- cially in the first 3 years of life
mal range.”
Caries Formation
• Possible etiologies include hypothyroidism,
• Chronic infectious disease.
hypopituitarism, ectodermal dysplasia, and
• Pathogenesis: Tooth-adherent bacteria (most
rickets.
commonly Streptococcus mutans) metabolize
sugars to produce acid that leads to deminer-
Odontogenic Infection alization of the tooth structure.
Risk Factors
Etiology
• Bottle propping (affects predominantly cen-
• Caries are typically the primary cause of
tral incisors)
odontogenic infections.
• Low-income households ◦◦ Reimplant the tooth into the socket as

• Excessive consumption of sugar soon as possible.
• Genetic factors ◦◦ If not possible, preserve the tooth in
saliva, milk, or normal saline.
Prevention ◦◦ The goal is to maintain viability of the
• Dental visit within the first 6 months of first periodontal ligament fibers.
tooth eruption and no later than 1 year of age. ◦◦ Child should be transported to a dental
• Tooth brushing is suggested twice daily with office or the nearest emergency room.
an age-appropriate size of fluoridated tooth-
paste (discourage swallowing toothpaste to
prevent fluorosis) NECK
• Avoid high-frequency consumption of high-
sugar liquids/solid foods. ervical Lymphadenitis
C
• Recommend weaning from bottle between 12
and 18 months and transitioning to a cup. Pathogens
• Viral: EBV (most common virus), CMV, HSV,
Fluoride Supplementation adenovirus, enterovirus, roseola, rubella, HIV
• Dental fluorosis occurs during the develop- • Bacterial: group A Streptococcus (most com-
ment of the tooth (critical ages between 0 and mon), Staphylococcus aureus
6 years of age, with most important being
between 15 and 30 months) [14] Clinical Presentation
• Be aware that access to fluoridated water may • Fevers (typically low grade for viral), mal-
be limited in some areas in the USA. aise, tender and mobile cervical nodes
• Optimal water fluoridation is 0.7 ppm of (Fig. 18.13)
fluoride.
• If there’s limited access to fluoridated water, Diagnosis
supplementation may be considered, especially • History and physical examination
for patients between 15 and 30 months of age. • Possible aspiration for culture and sensitivity
Dental Trauma and Avulsions

Primary Tooth Avulsion
• Refer to the dentist for follow-up to rule out
any associated problems.
• Avoid reimplantation of primary avulsed
tooth.
• Permanent tooth avulsion (it is a true dental
emergency) [15]:
–– Reimplantation of tooth:
◦◦ If reimplanted within 5 min, tooth sur-
vival rate is 85–97%
◦◦ If reimplanted after 1 h of injury, tooth is
unlikely to survive.
–– Instructions for avulsed permanent tooth:
Fig. 18.13 9-year-old boy presenting with a high fever of
◦◦ Gently wash the avulsed tooth with no 104 ° F, malaise, and tender large bacterial cervical
rubbing or brushing. lymphadenopathy
Complications • Fever (often mild), malaise

• Cellulitis, abscess, internal jugular vein
thrombosis, mediastinitis, sepsis Diagnosis
• Serology (IgG henselae titers), culture
Treatment (Warthin-Starry stain), polymerase chain
• Viral: supportive reaction (PCR) assay, histopathology
• Bacterial:
–– Antibiotics Treatment
–– Incision and drainage if there is an abscess • Supportive (typically self-limiting)
formation • Antibiotic therapy in immunocompromised
patients
• Surgical aspiration for culture, but avoid for-
Infectious Mononucleosis mal incision and drainage to prevent fistula/
sinus formation
• Caused by EBV
Atypical Mycobacteria
Clinical Presentation • Pathogen: Mycobacterium avium complex,
• Fever, pharyngitis, and lymphadenopathy. M. scrofulaceum, M. kansasii
• Symmetric cervical adenopathy (most com-
monly, posterior triangle nodes) Risk Factors
• Axillary and inguinal nodes may also be • Young children, immunocompromised.
involved. • If patient is less than 1 year old, consider
• Fatigue, malaise, splenomegaly. alternative diagnosis such as Langerhans
histiocytosis.
Diagnostic Tests
• Monospot test (“heterophile antibody”): Clinical Presentation
–– High false-negative rate if obtained early on • Asymptomatic.
in illness or in children under 4 years of age • Unilateral cervical lymphadenopathy, preau-
• Elevated immunoglobulin M titer to viral ricular adenopathy, commonly located on the
capsid antigen (IgM-VCA) indicates acute face over body of mandible.
infection. • Adhesive to overlying skin; overlying skin is
erythematous in advanced disease.
• Lesions often described as having “viola-
Cat Scratch Disease ceous” coloring.
• Pathogen: Bartonella henselae Diagnosis

• Acid-fast stain, culture (requires 2–4 weeks
Clinical Presentation for results)
• Present ~2 weeks after cat scratch or bite
(usually from a kitten) Treatment
• Papular lesion at primary scratch site associ- • Watchful waiting (typically takes months to
ated with cervical lymphadenopathy (tender resolve)
initially and then becomes painless)—may • Excision or incision and curettage (avoid
ulcerate and form fistula incision and drainage, as fistula can result)
Other Causes, Lymphadenitis • Presentation: febrile illness, ulceroglandular

syndrome (painful regional lymphadenopathy
• Tuberculosis: in children, less common than and an ulcerated skin lesion)
atypical mycobacterium • Treatment: streptomycin
• Kawasaki disease (mucocutaneous lymph
node syndrome):
–– Acute vasculitis affecting multiple organs
in children Castleman’s Disease
–– Diagnosis:
• Lymphoproliferative disorder localized to a
◦◦ Must have five of the following:
single node (unicentric) or systemically
▪▪ Fever > 5 days (high)—absolute criteria
(multicentric)
▪▪ Erythematous rash
• Polyclonal proliferation of B-lymphocytes
▪▪ Conjunctival injection
• Unicentric:
▪▪ Oropharyngeal changes
–– Typically asymptomatic—presents with an
▪▪ Peripheral extremity changes (indura-
enlarged lymph node (20% in the neck)
tion or desquamation)
–– CT scan shows a well-circumscribed mass.
▪▪ Cervical lymphadenopathy
–– Pathology demonstrates nodal expansion.
▪▪ Echocardiogram
–– Surgical removal is curative 90% of the
▪▪ High risk of developing coronary
time.
aneurysm or myocardial infarction
• Multicentric:
(consider IVIG and aspirin therapy,
–– May be associated with HIV, Kaposi
along with EKG and echo)
sarcoma-associated herpesvirus, and/or
human herpesvirus type 8.
Kikuchi – – No standard treatment. May include antivi-
rals, chemotherapy, corticosteroids, and
• Rare disease of unknown etiology monoclonal antibodies.
• Presentation: young women, cervical and – – Refer to oncology.
generalized lymphadenopathy, fever, night
sweats, rash, weight loss, nausea, and
vomiting Lymphoma
• Diagnosis: lymph node biopsy—histiocytic
• Most common pediatric malignancy of the
necrotizing lymphadenitis
head and neck.
• Treatment:
• Lymphoproliferative disorder.
–– No effective treatment, typically resolves
• Hodgkin and non-Hodgkin lymphoma may
within 1–4 months.
present with cervical lymphadenopathy.
–– Symptom control with steroids.
–– Follow-up is necessary, as patients with Clinical Presentation
Kikuchi are at higher risk of developing • Nodal masses—may present with cervical
systemic lupus. nodes
• Hodgkin: contiguous lymph nodes
• Non-Hodgkin lymphoma: may present with
Tularemia
extranodal involvement (i.e., enlarged tonsils,
• Pathogen: Francisella tularensis base of tongue, enlarged thyroid, etc.)
• Transmission: contact with infected animal (i.e., • Constitutional symptoms: fevers, night
rabbits or hamsters) sweats, weight loss
Diagnosis • Elevates with tongue protrusion

• History and physical examination (pathognomonic)
• Evaluation of all nodal sites
• Open biopsy (rather than fine needle Complications
biopsy)—fresh tissue is required for • May become infected
immunochemistry • Rare malignant potential
Management Treatment
• If positive for lymphoma, refer to oncology. • Treat infection with antibiotics (avoid inci-
sion and drainage)
• Surgical removal when not infected (Sistrunk
Thyroglossal Cyst procedure)
Definition
• Failed obliteration of the thyroglossal duct B
ranchial Cleft Cyst
(embryologic tract from the foramen cecum
of the tongue to the thyroid) • Alterations of the branchial apparatus result-
ing in cysts, sinuses, or fistula
• Midline neck mass (often cystic, may be Presentation
solid, mixed, or inflamed)—surrounding the • Unilateral (most common)
hyoid bone and superior to the thyroid • Anterior, lateral neck mass (typically anterior
(Fig. 18.14) to sternocleidomastoid muscle), sinus, or
fistula
• May become infected with drainage (associ-
ated with URI)
Treatment
• Treat infection with antibiotics (avoid inci-
sion and drainage)
• Complete surgical excision of cyst, sinus, and
fistula tract once infection resolves.
Lymphatic Malformation
• Also known as cystic hygroma and lymphan-
gioma (outdated terms)
• Etiology: abnormal lymphatic development
Presentation
• May occur anywhere in the body
• Soft, painless, multiloculated, compressible
mass that transilluminates:
Fig. 18.14 Typical appearance of a neck mass associated –– In the cervical region, posterior triangle is
with underlying thyroglossal duct cyst. It is important to most common.
obtain an ultrasound of the neck to confirm the presence of a • Present at birth or shortly thereafter:
normal thyroid gland prior to removal of the thyroglossal
duct cyst in order to avoid inadvertent removal of the only –– Often enlarges after URI
thyroid tissue
• Associated symptoms related to mass com- nearby structures (hoarseness) are very rare
pression of nearby structures in children.
Workup
Imaging: MRI preferred • Ultrasound of the thyroid and neck preferred
Management as initial imaging, often with fine needle aspi-
• Observation if small and with no associated ration (plus molecular studies) of thyroid mass
complications • Thyroid function tests and thyroid antibody
• Sclerosing agents studies (in consultation with endocrinology)
• Surgical excision • Complete metabolic panel (including
calcium)
• Chest radiograph (lung metastasis, most com-
Thyroid Carcinoma
mon site of distant disease)
Presentation
Pathology
• Midline anterior mass, may have associated
• Papillary (most common), follicular, medul-
lateral neck masses (lymph nodes):
lary, anaplastic
–– Painless, solid, fixed, asymptomatic mass.
Management
–– Thyroid nodules in children reportedly
• Multidisciplinary care team referral (endocri-
have a ~25% incidence of malignancy.
nology, genetics, otolaryngology/pediatric
–– Neck metastasis is frequently the present-
surgery)
ing symptom.
• Treatment is surgical, with additional therapy
• More common in females (2 to 3 times), ado-
pending the pathology results and patient
lescents, and those with personal history of
factors.
autoimmune thyroid disease.
• History should include radiation exposure
and family history. Acute Laryngitis
• May be associated with genetic syndromes:
–– Multiple endocrine neoplasia type 2 Etiology
(MEN2) syndromes: medullary thyroid • Infectious (most commonly viral, may have
carcinoma (MTC): secondary bacterial infection)
◦◦ MEN2A: MTC, pheochromocytoma, • Fungal infection (immunocompromised
parathyroid adenoma, or hyperplasia child, steroid inhaler use)
◦◦ MEN2B: MTC, pheochromocytoma, • Vocal strain (secondary to screaming/
Marfanoid habitus, mucosal neuromas yelling)
◦◦ Familial medullary thyroid cancer: MTC Management
only, affects 5–35% of MEN2 families • Generally self-limiting.
–– Familial adenomatous polyposis: papillary • Optimize hydration.
form, may be in younger age • Humidification.
–– Cowden syndrome (PTEN hamartoma • Saltwater gargles.
tumor syndrome): papillary or follicular • Treat with antibiotics or antifungals if bacte-
form rial or fungal infection is suspected.
• Associated symptoms related to mass com- • Referral to otolaryngology if it persists
pression (dysphagia, dyspnea) or invasion of > 4 weeks.
Chronic Laryngitis/Hoarseness Etiology

• Iatrogenic (most common in pediatric
• Definition: symptoms of hoarseness, dyspho- patients): patent ductus arteriosus ligation,
nia, and/or vocal fatigue for > 3 months cardiothoracic surgery, tracheoesophageal
• Associated symptoms: chronic cough, fre- fistula repair, thyroidectomy
quent throat clearing, postnasal drip • Idiopathic (most common in newborns/
sensation infants)
• Neurologic (e.g., Arnold-Chiari malforma-
Etiology tion, posterior fossa tumor)
• Typically noninfectious causes (most com- • Viral
mon vocal fold screamers’ nodules) • Autoimmune
• Gastroesophageal reflux disease/laryngopha- • Pulmonary lesion or cor pulmonale (Ortner’s
ryngeal reflux disease syndrome)
• Recurrent respiratory papillomatosis (caused
by HPV 6 and HPV 11) Diagnosis
• Environmental irritants (second-hand smoke, • Refer to ENT for flexible laryngoscope,
vape, huffing) which will assess for vocal fold mobility,
• Environmental allergies mucosal lesions, and laryngeal masses.
• Postnasal drip/rhinitis
• Medications (e.g., inhaled steroids, chemo- Workup of Vocal Fold Paralysis
therapy, anti-cholinergic medications) • Observation (if known iatrogenic cause)
• Rarely, chronic systemic disease (e.g., • Chest radiograph
amyloid, granulomatosis with polyangi-
• Modified barium swallow (to assess for
itis), lymphovascular malformation, or aspiration)
malignancy • MRI brain
• CT for the neck and chest
Diagnosis
• ENT referral for flexible nasolaryngoscopy Treatment
• Observation:
Management –– Monitor for signs of aspiration or respira-
• Treat underlying cause. tory distress.
• Empiric treatment of GERD/ laryngopharyn- – – Monitor for signs of recovery.
geal reflux (LR) is often considered if clinical • Surgery:
history is suggestive. –– Tracheostomy (bilateral)
–– Vocal fold surgery
–– Hypoglossal to recurrent laryngeal nerve
Vocal Fold Paralysis reanastomosis
Background
• One of the most common laryngeal abnor- Stridor
malities in childhood
• Unilateral or bilateral paralysis of the vocal • Noisy breathing, which often implies turbu-
fold lent airflow through an extrathoracic airway
• Congenital or acquired obstruction
• Stertor: Distinct from stridor. Stertor is more

often a muffled, congested upper airway noise
emanating from the nose, nasopharynx, or
oropharynx.
Etiology
• Inspiratory: most often above the level of the
vocal folds
• Expiratory: most often in the trachea
• Biphasic: most often at the level of the vocal
folds (glottis) or the subglottis
Differential Diagnosis
• Acute—most often of infectious or inflam-

matory cause: number 1, croup (parainflu-
enza virus); influenza virus type A or B, RSV,
rhinovirus, epiglottitis, bacterial tracheitis,
angioedema, foreign body Fig. 18.15 Mild to moderate laryngomalacia as evidenced
• Chronic—most often of an anatomic cause: by tubular (“omega-shaped”) epiglottis, knobby, or bulky
arytenoid cartilages and tight aryepiglottic folds
number 1, laryngomalacia; vocal fold immo-
bility (unilateral or bilateral), vascular ring,
Management
tracheomalacia, papilloma, subglottic steno-
• Treat underlying cause.
sis, laryngeal web, tracheal stenosis, subglot-
• Empiric treatment of GERD/LPR often con-
tic hemangioma
sidered if clinical history is suggestive.
Diagnosis
• History: Symptoms related to positioning,
aryngomalacia
L
feeding; apparent life-threatening events
(ALTEs)/brief, resolved, unexplained events • Collapse of the supraglottic airway (epiglot-
(BRUEs), cyanotic episodes, crying/agita- tis, arytenoid cartilages, or both) during inspi-
tion, and trajectory are especially important. ration secondary to immature framework
• Physical exam: vitals including pulse oxime- (Fig. 18.15)
try, growth curve, complete head and neck • Most common congenital lesion of the
evaluation; cardiopulmonary evaluation larynx.
including inspection for retractions, abdomi- • High-pitched inspiratory stridor usually begins
nal breathing, respiratory distress. around 4–6 weeks, peaks around 6–8 months,
• ENT referral for flexible nasolaryngoscopy and resolves by 24 months of age.
and further evaluation. • Higher incidence of GERD
• If pathology is thought to be below the level
of the vocal folds (e.g., subglottic stenosis), Symptoms
operative laryngoscopy and bronchoscopy • Stridor, feeding difficulty, sleeping difficulty,
are also needed to evaluate the airway. need for frequent repositioning (increased
• If there’s suspicion of vascular ring, refer to when supine), increased work of breathing/
cardiology and consider of CT angiography retractions, failure to thrive, cyanotic episodes
of the chest. (rare); may worsen in the setting of URI
Management • Midline neck mass is most likely a thyroglos-

• 90% of patients treated with conservative sal duct cyst secondary to the embryologic
management and time; referral to ENT for derivative at the base of the tongue (foramen
flexible nasolaryngoscopy and consideration cecum). Ultrasound should be performed to
of surgical management (airway evaluation, confirm the presence of a normal thyroid in
possible supraglottoplasty) if symptoms are its expected location.
moderate/severe • The most common congenital lesion of the
• Surgery considered for failure to thrive, larynx is laryngomalacia; most children will
hypoxemia, severe retractions, sleep apnea outgrow the diagnosis by 24 months of age.
• Cough, rhinorrhea, and diarrhea are more
common with viral than with bacterial
PEARLS AND PITFALLS pharyngitis.
• The diagnostic gold standard for bacterial
• Otalgia is an expected phenomenon for up to pharyngitis is a throat culture.
2 weeks following tonsillectomy. • Diagnosis of PTA is a clinical diagnosis based
• Hematoma of the external ear (pinna) neces- on history (double worsening, URI symptoms
sitates same-day referral for emergency care > 5 days prior to new symptoms) and physical
because of the potential for permanent defor- exam (hot potato voice, trismus, uvular
mity secondary to avascular necrosis of the deviation)
cartilage. • The American Academy of Pediatrics recom-
• First-line therapy for AOM is amoxicillin mends screening for OSA by history (snor-
(90 mg/kg/day divided twice a day) × 10 days. ing, daytime symptoms) during well-child
• Caregivers should be instructed to warm ear checks. Symptoms may include irritability,
drops in their hands prior to administration to hyperactivity, daytime sleepiness, and noc-
decrease patient discomfort. turnal enuresis; this is a different constella-
• Patients with benign paroxysmal vertigo of tion of symptoms than in adult patients.
childhood are at increased risk of typical • Ankyloglossia often manifests as discomfort
migraine headache as adolescents and adults. in the mother’s nipples.
• CHARGE is the most commonly associated • Children with cleft palate are at an increased
congenital anomaly with choanal atresia. risk of developing Eustachian tube dysfunc-
• In children, 90% of epistaxis occurs from the tion resulting in OME and recurrent AOM.
anterior septum (Kiesselbach plexus), and the • Eruption cysts present as blue or purple com-
most frequent cause is digital trauma. pressible cysts at the site of an erupting decid-
• Nasal fractures are the most common facial uous or permanent tooth. These are often
fracture in children. self-limiting but may require treatment if they
• Presence of nasal polyps in children should become infected or limit feeding.
prompt testing for cystic fibrosis.
• Nasal saline rinses should be used with cau- Acknowledgement The authors gratefully
tion in children with history of aspiration. acknowledge the contributions of Josee Paradis,
• The most common cause of a neck mass in the MD, Paediatric Surgery, London Health Sciences
pediatric population is cervical lymphadenitis. Centre—Victoria Hospital, London, Ontario,
• If there is clinical suspicion for lymphoma, Canada, to the first edition of this chapter, many of
systemic steroids should be avoided, as these which have been incorporated into this edition as
may interfere with flow cytometry results. well.
References 8. Chow AW, Benninger MS, Brook I, Brozek

JL, Goldstein EJ, Hicks LA, et al. Infectious
1. Wang RY, Earl DL, Ruder R, Graham JM Diseases Society of America. IDSA clinical
Jr. Syndromic ear anomalies and renal ultra- practice guideline for acute bacterial rhinosi-
sounds. Pediatrics. 2001;108(2):E32. nusitis in children and adults. Clin Infect Dis.
2. Uhari M, Mantysaari K, Niemela M. A 2012;54(8):e72–e112.
meta-analytic review of the risk factors 9. Choby BA. Diagnosis and treatment of strep-
for acute otitis media. Clin Infect Dis. tococcal pharyngitis. Am Fam Physician.
1996;22(6):1079. 2009;79(5):383–90.
3. Lieberthal AS, Carroll AE, Chonmaitree T, 10. Stewart EH, Davis B, Clemans-Taylor BL,

Ganiats TG, Hoberman A, Jackson MA, et al. Littenberg B, Estrada CA, Centor RM. Rapid
The diagnosis and management of acute oti- antigen group a streptococcus test to diagnose
tis media. Pediatrics. 2013;131(3):e964–99. pharyngitis: a systematic review and meta-
Erratum Pediatrics. 2014;133(2):346. Dosage analysis. PLoS One. 2014;9(11):e111727.
error in article text. 11. Baugh RF, Archer SM, Mitchell RB, Rosenfeld
4. Rosenfeld RM, Shin JJ, Schwartz SR, Coggins RM, Amin R, Burns JJ, American Academy
R, Gagnon L, Hackell JM, et al. Clinical of Otolaryngology-Head and Neck Surgery
practice guideline: otitis media with effu- Foundation, et al. Clinical practice guideline:
sion (update). Otolaryngol Head Neck Surg. tonsillectomy in children. Otolaryngol Head
2016;154(1 Suppl):S1–S41. Neck Surg. 2011;144(1 Suppl):S1–30.
5. Rosenfeld RM, Schwartz SR, Pynnonen MA, 12. Ramos SD, Mukerji S, Pine HS. Tonsillectomy
Tunkel DE, Hussey HM, Fichera JS, et al. and adenoidectomy. Pediatr Clin N Am.
Clinical practice guideline: tympanostomy 2013;60(4):793–807.
tubes in children. Otolaryngol Head Neck 13. Marcus CL, Moore RH, Rosen CL, Giordani
Surg. 2013;149(1 Suppl):S1–S35. B, Garetz SL, Taylor HG, Childhood
6. Alford RL, Arnos KS, Fox M, Lin JW, Palmer Adenotonsillectomy Trial (CHAT), et al.
CG, Pandya A, ACMG Working Group on A randomized trial of adenotonsillectomy
Update of Genetics Evaluation Guidelines for childhood sleep apnea. N Engl J Med.
for the Etiologic Diagnosis of Congenital 2013;368(25):2366–76.
Hearing Loss; Professional Practice and 14. Hong L, Levy SM, Broffitt B, Warren JJ,

Guidelines Committee, et al. American Kanellis MJ, Wefel JS, Dawson DV. Timing
College of Medical Genetics and Genomics of fluoride intake in relation to develop-
guideline for the clinical evaluation and etio- ment of fluorosis on maxillary central inci-
logic diagnosis of hearing loss. Genet Med. sors. Community Dent Oral Epidemiol.
2014;16(4):347–55. 2006;34(4):299–309.
7. Wald ER, Applegate KE, Bordley C, Darrow 15. Andersson L, Andreasen JO, Day P, Heithersay
DH, Glode MP, Marcy SM, American G, Trope M, Diangelis AJ, et al. International
Academy of Pediatrics, et al. Clinical practice Association of Dental Traumatology guide-
guideline for the diagnosis and management of lines for the management of traumatic dental
acute bacterial sinusitis in children aged 1 to injuries: avulsion of permanent teeth. Dental
18 years. Pediatrics. 2013;132(1):e262–80. Traumatol. 2012;28(2):88–96.
Cardiology
19
Grace Kung, Allison Hill, and Jennifer Su
CHEST PAIN –– Distant heart sounds or pericardial friction

rub
Background –– Murmur:
• Chest pain in children is rarely due to cardiac ◦◦ Harsh systolic ejection murmur
disease ◦◦ Pansystolic murmur
• The history and physical examination can ◦◦ Continuous murmur
establish the diagnosis of noncardiac chest –– Gallop rhythm
pain in the majority of cases –– Peripheral edema
• 20% to 45% of cases of pediatric chest pain
are idiopathic
ardiac Disorders Associated
C
with Chest Pain
Red Flags for Cardiac Chest Pain
• Coronary artery diseases (ischemia or
• History infarction)
–– Exertional symptoms (chest pain, syncope, –– History of Kawasaki disease (coronary
fatigue) arteritis)
–– Pain associated with palpitations or fever –– History of transposition of great arteries
–– Pain that radiates to the back, jaw, and left s/p arterial switch
arm/shoulder or increases when supine –– Anomalous origin of the coronary arteries
–– Cocaine/amphetamine use –– Coronary artery fistula
–– Family history of sudden unexplained –– Cocaine abuse
death, cardiomyopathy, or inherited –– Coronary calcinosis
arrhythmias such as long QT syndrome –– Takayasu arteritis
• Abnormal cardiac exam • Infections/autoimmune disorders
–– Ill-appearing –– Pericarditis
–– Tachycardia –– Myocarditis
–– Narrow pulse pressure –– Systemic lupus erythematosus, juvenile
–– Hypotension rheumatoid arthritis
–– Pulsus paradoxus (PP) • Arrhythmias
–– Supraventricular tachycardia (SVT)
G. Kung (*) · A. Hill · J. Su –– Ventricular tachycardia
Division of Cardiology, Department of Pediatrics, Children’s
Hospital of Los Angeles, USC Keck School of Medicine, • Other cardiac abnormalities
Los Angeles, CA, USA –– Aortic stenosis
e-mail: gkung@chla.usc.edu

644 G. Kung et al.
–– Aortic dissection (collagen vascular dis- G astrointestinal Causes of

ease such as Marfan syndrome) Chest Pain
–– Hypertrophic cardiomyopathy (HCM)
–– Pulmonary hypertension • Recent foreign body ingestion
–– Severe pulmonary stenosis • Reflux esophagitis
• Clinical presentation:
–– Burning, substernal in location
Noncardiac Causes of Chest Pain –– Worsened by reclining or eating spicy
foods
• Musculoskeletal causes of chest pain: one of
–– Pain related to meals
the most common diagnoses in children who
have chest pain:
–– Costochondritis Psychogenic Causes of Chest Pain
–– Strained chest wall muscles following
coughing, exercise, sports participation, or • Anxiety
carrying heavy books or backpack • Stress
–– Direct trauma causing sternal or rib contu-
sion or rib fracture
• Clinical presentation: Miscellaneous Causes of Chest Pain
–– Chest wall tenderness with palpation.
–– History of trauma. • Sickle cell disease may lead to vaso-occlusive
–– Pain may be pleuritic, bilateral, sharp, and crises or acute chest syndrome.
exaggerated by physical activity. • Shingles may result in severe chest pain.
–– Pain may persist for several months.
–– Quality of pain is unchanged with
exertion. Clinical Approach to Chest Pain
• Comprehensive history:
Respiratory Causes of Chest Pain –– Characteristics of the pain:
◦◦ Frequency, location, quality, and sever-
• Asthma ity of the pain
• Pneumonia ◦◦ Timing: daily activity, sleep, exercise
• Pulmonary embolism: –– Associated symptoms: exercise intoler-
–– History of oral contraceptive use ance, fatigue, palpitations, shortness of
–– Hypercoagulable state breath, dizziness, or syncope
• Pneumothorax: –– Family history for heritable diseases affect-
–– Marfan syndrome ing the heart or lungs, i.e., sudden death,
• Pleural effusion/hemothorax deafness, seizures, cardiomyopathy, or
• Clinical presentation: asthma
–– Tachypnea –– A prior history of structural or acquired
–– Dyspnea heart disease
–– Hypoxia –– Prior history of cardiac surgery
–– Fever –– Medication or drug use
–– Pleuritic pain • Physical examination:
–– Cough –– Vital signs
–– Hemoptysis –– Signs of heart failure or congestion
19 Cardiology 645
–– Abnormal cardiac findings • Cardiac disorders:

–– Chest wall palpation –– Hypertrophic obstructive cardiomyopathy
• Electrocardiogram (ECG): –– Aortic stenosis
–– Further testing as indicated: echocardiogram, –– Pulmonary hypertension
exercise stress testing, 24 h Holter monitor, –– Coronary artery anomalies
pulmonary function testing, blood tests, chest –– Myocarditis
radiography (CXR), toxicology screen –– Arrhythmias
–– Sinus node dysfunction
–– Complete heart block
SYNCOPE –– Rapidly conducting supraventricular
tachycardia
Background –– Ventricular tachycardia (torsades de
• Syncope is a temporary loss of consciousness pointes) or fibrillation
that may be due to cerebral hypoperfusion or • Noncardiac mechanisms: breath-holding
neurologic disorders. spells, hyperventilation, heat stroke, hypogly-
• Anoxic seizures may rarely occur. cemia, anaphylaxis, intoxication.
• Conditions that mimic syncope: migraines, sei
Causes of Syncope zures, narcolepsy, or psychological disorders.
• Vasovagal/neurocardiogenic: impaired response
of the autonomic nervous system. Initial Evaluation
• The most common form of syncope in • History (including preceding events, descrip-
children. tion of the event, past history, family
• Mechanism is an exaggerated reflex in vaso- history)
motor tone and heart rate causing vasodila- • Physical exam: vitals, including orthostatic
tion, hypotension, and bradycardia. vital signs
• Clinical presentation: • ECG
–– Triggers: • Red flags for cardiac syncope:
◦◦ Standing from a supine/seated position. –– No prodrome
◦◦ Prolonged standing. –– Sudden onset of palpitations, shortness of
◦◦ Dehydration/heat. breath, or chest pain before syncope
◦◦ Urination (micturition syncope). –– Syncope during exertion, swimming, or
◦◦ Hairbrushing. supine
◦◦ Intense emotion or pain (blood draw). –– Episode brought on by sudden startle
◦◦ Pregnancy. –– Exercise intolerance and fatigue
–– Prodrome (lightheadedness, dizziness, –– Young age, < 10 years (especially less than
weakness, pallor, nausea, cold sweat, 6 years)
blurred vision, or hearing loss) precedes –– Previous heart disease
syncope. –– Family history of cardiomyopathy, chan-
–– Relief from all symptoms usually occurs if nelopathy, or sudden death in a close rela-
the patient lies down during prodrome. tive < 50 years old
–– Brief period of unconsciousness. –– Abnormal physical examination
–– Normal physical examination ± orthostatic –– Abnormal ECG
hypotension.
646 G. Kung et al.
Further Evaluation C ARDIAC ARRHYTHMIAS

• 24-hour Holter or 30-day event monitoring if
history suggests arrhythmia
(FIGS. 19.1, 19.2, 19.3, 19.4, 19.5,
• Echocardiogram if physical examination or 19.6, 19.7, 19.8, 19.9, 19.10, 19.11,
ECG is abnormal or if family history is AND 19.12)
concerning
Background
Treatment of Vasovagal Syncope • Although most childhood arrhythmias are
• Increase fluid and salt intake—results in no benign, prompt and correct diagnosis of a
further episodes in 90% patients. serious rhythm disturbance in a child can be
• Postural awareness; avoid venous pooling. lifesaving.
• Fludrocortisone. • Key history for arrhythmias:
• Midodrine –– Initiation/termination of tachycardia:
• Beta-blockers
Fig. 19.1 13-year-old child with sinus arrhythmia. Arrows show the acceleration and deceleration of heart rate
Fig. 19.2 Newborn with irregular heart rate. Diagnosis: atrial flutter with 4:1 conduction
19 Cardiology 647
Fig. 19.3 15-year-old child with atrial septal defect. Diagnosis: atrial fibrillation (irregularly irregular with no clear P-wave)
Fig. 19.4 12-year-old child with palpitations. Diagnosis: supraventricular tachycardia (regular narrow complex
tachycardia)
648 G. Kung et al.
Fig. 19.5 8-year-old boy with palpitation. Diagnosis: Wolff-Parkinson-White syndrome (short PR with delta wave)
19 Cardiology 649
Fig. 19.6 11-year-old with long QT syndrome. Brackets point out the RR and QT intervals used to calculate the prolonged
QTc
Fig. 19.7 6-year-old child presented with difficulty in breathing. Diagnosis: ventricular tachycardia (wide complex) in the
setting of myocarditis
650 G. Kung et al.
Fig. 19.8 Rhythm strips demonstrating (a) first-degree prolongation prior to dropped QRS) with arrows pointing to
atrioventricular (AV) block (prolonged PR interval shown the P-waves, (c) complete heart block (complete AV disso-
with a bracket), (b) Wenckebach conduction (progressive PR ciation) with arrows pointing to the P-waves
Fig. 19.9 14-year-old child with chest pain. Diagnosis: Diffuse ST elevation, perimyocarditis
19 Cardiology 651
Fig. 19.10 17-year-old child with hypertrophic cardiomyopathy (LVH with abnormal T-waves shown by an arrow in lead
V6)
Fig. 19.11 16-year-old patient with tetralogy of Fallot repaired in infancy. Diagnosis: normal sinus rhythm with right
bundle branch block
652 G. Kung et al.
Fig. 19.12 5-month-old infant with atrioventricular canal (northwest axis shown in leads I and aVF with arrows)
◦◦ Abrupt onset and termination are sug- Sinus Rhythm and Sinus Arrhythmia
gestive of an arrhythmia.
◦◦ Gradual onset and termination are sug- Background
gestive of normal variation. • Sinus arrhythmia is a normal finding in
–– Symptoms: syncope, dizziness, fatigue, healthy children.
shortness of breath, chest discomfort • Decrease in SA node firing subsequent to
–– Arrhythmia triggers: exercise, startle/loud activation of the vagus nerve by exhalation.
noises, swimming
–– History of heart disease Clinical Presentation
–– Medication history • Asymptomatic.
–– Family history: sudden death, pacemaker, • The heart rate varies with respiration.
deafness, seizures • ECG shows sinus rhythm with a prolongation
• ECGs—the key to interpretation is system- of the RR interval during exhalation.
atic review:
–– Rate
–– Rhythm (P-wave axis, atrioventricular Premature Atrial Contractions (PACs)
[AV] synchrony, premature beats,
Background
irregularity)
• Premature atrial contractions (PACs) are very
–– QRS axis
common in pediatric patients and are benign
–– Presence of atrial enlargement
when isolated (i.e., only single beats with no
–– Intervals: PR, QRS, and QT corrected
consecutive or sustained tachycardia).
–– Presence of left ventricular hypertrophy
(LVH) or right ventricular hypertrophy Causes
(RVH) • Idiopathic (most common)
–– ST and T-wave abnormalities • Electrolyte imbalances
19 Cardiology 653
• Intracardiac lines (peripherally inserted cen- • Can be difficult to see when the AV node is
tral catheter [PICC] or central lines with the conducting 1:1 (i.e., with ventricular rates of
tip in the right atrium [RA]) > 200) or 2:1 (i.e., with ventricular rates of
150–200 bpm).
Clinical Presentation • Adenosine will not terminate the atrial flutter
• Asymptomatic or feeling a “skipped beat” or but can aid in diagnosis by temporarily block-
“pause,” often followed by a strong beat ing the AV node and unveiling the sawtooth
pattern on ECG.
ECG
• Premature, inverted, or oddly shaped P-waves Management
• Urgent cardiac evaluation and treatment.
Management • If the patient is unstable, initiate synchro-
• No additional evaluation is necessary. nized cardioversion.
• If the patient is bothered by PACs, reassure • If the patient is stable, evaluate for thrombus
and avoid triggers. by echo (depending on suspected duration of
flutter).
• Synchronized electrical cardioversion if no
Atrial Flutter thrombus is present.
Background • Antiarrhythmic drugs can be used to control
• Atrial rates usually 300–400 beats/min (can the ventricular rate during a course of antico-
be slower in older children or those with atrial agulation if a thrombus is present.
scars from cardiac surgery) with variable • Radiofrequency catheter ablation can be cura-
conduction so that the ventricular rate is tive for recurrent episodes of atrial flutter.
slower than the atrial rate.
• Atrial flutter is caused by a reentrant circuit in
Atrial Fibrillation (AF)
the atrium.
Background
• AF is uncommon in young children.
• Infants may present with congestive heart
failure. Causes
• Older children may have palpitations, dizzi- • Other types of supraventricular tachycardia
ness, syncope, chest pain, and shortness of (SVT) can degenerate into AF.
breath. • Hyperthyroidism.
• The major clinical clue is usually a fixed rapid • Electrolyte disturbance such as
heartbeat that is between 150 and 200 bpm hypomagnesemia.
(flutter with 2:1 conduction). • Substance abuse.
• Prolonged atrial flutter or fibrillation (usually • Hypertrophic cardiomyopathy.
> 24 h) can result in thrombus formation • Inherited arrhythmias (long QT/Brugada/
within the left atrium. short QT syndromes).
• Can be seen in certain types of inherited
arrhythmias (Brugada syndrome). Clinical Presentation
• AF generally is not life-threatening except if
Diagnosis the patient has a rapidly conducting acces-
• Classic inverted “sawtooth” pattern on ECG, sory bypass tract (i.e., Wolff-Parkinson-White
best seen in leads II, III, and aVF. [WPW] syndrome on baseline ECG).
654 G. Kung et al.
• Palpitations. Clinical Presentation of Typical SVT

• Chest pain. • Infant:
• Syncope. –– Heart rates of 200–270 beats/min
• Irregularly irregular rhythm. –– Poor feeding/vomiting, pallor, irritability,
• Prolonged atrial fibrillation or flutter (usually and lethargy
> 24 h) can result in clot development within –– Congestive heart failure with hemody-
the left atrium. namic decompensation if prolonged
• School-aged children:
Diagnosis –– Sudden-onset palpitations, heart or throat/
• Absent or very low-voltage (i.e., small), fast, neck pounding, “beeping in the chest”
and irregular P-waves with irregularly irregu- –– Chest discomfort
lar RR intervals on ECG –– Shortness of breath
–– Exercise intolerance
Management –– Heart rate: 180–240 beats/min
• Urgent cardiac evaluation and treatment.
• If the patient is unstable, initiate synchro- Diagnosis
nized cardioversion. • ECG:
• If the patient is stable, evaluate for thrombus –– Usually narrow complex (< 80 ms) tachy-
by echo (depending on suspected duration of cardia with a fixed rapid rate.
atrial fibrillation). –– P-waves are often difficult to see but may
• Synchronized electrical cardioversion if no be seen as sharp deflections within the
thrombus is present. T-waves.
• Antiarrhythmic drugs can be used to control –– Baseline ECG can be normal or can have
the ventricular rate during a course of antico- WPW (in accessory pathway-mediated
agulation if a thrombus is present. SVT).
• Radiofrequency catheter ablation can be con-
sidered to evaluate and treat other SVT sub- Management
strates that may have induced atrial • Acute management of an SVT episode:
fibrillation. –– If patient is stable:
◦◦ Vagal maneuvers, i.e., place an ice bag
on the face over the forehead/eyes (rac-
Supraventricular Tachycardia (SVT) coon distribution) for 5–15 s or Valsalva.
◦◦ Adenosine will terminate reentrant
Background SVTs that involve the AV node.
• SVT is defined as a rapid tachycardia origi- ◦◦ Remember to administer adenosine
nating above the bundle of His. quickly (via push with a flush quickly
• It occurs in as many as 1 in 250 children but thereafter) through a large-bore IV as
is often misdiagnosed due to the variety of centrally as possible to avoid breakdown
presentations. of adenosine by red blood cells prior to
reaching the heart.
Pathogenesis
◦◦ Verapamil can be used if > 1 year of age,
• Reentrant tachycardia using an accessory
but avoid calcium channel blockers in
pathway
infants due to the risk of hypotension
• AV nodal reentrant tachycardia (AVNRT),
and shock.
typically seen in adolescents
–– If patient is unstable, direct-current (DC)
• Ectopic atrial tachycardia
cardioversion
19 Cardiology 655
• Chronic management: • Widened QRS complex (total duration

–– Pediatric cardiology referral. > 0.12 s)
–– Ambulatory ECG monitoring devices (24 h • ST segment T-wave changes, generally
Holter monitors or event recorders) are directed opposite the major delta wave and
useful for diagnosing SVT in patients who QRS complex
have sporadic episodes.
–– Medical management: beta-blocker, calcium Treatment
channel blocker (in non-infants), digoxin (in • SVT treatment, as described before
the absence of an accessory pathway), or • Asymptomatic WPW:
other antiarrhythmic medications. –– Risk stratification (with exercise test or
–– Electrophysiology (EP) study with abla- Holter monitor) of the accessory pathway
tion procedure is the definitive treatment of to determine risk of sudden death
choice. –– Electrophysiology (EP) study and ablation
if high risk or preferred by the patient
Wolff-Parkinson-White (WPW)
Syndrome Sick Sinus Syndrome (SSS)
• WPW is a pattern seen on ECG due to an • This rhythm is a result of sinus node
aberrant accessory pathway that allows elec- dysfunction.
tricity to pass to the ventricles prior to going • Most often in patients who had prior cardiac
through the AV node. (especially extensive atrial) surgery or
• Associated conditions: cardiomyopathy cardiomyopathy.
(hypertrophic and LV noncompaction), • Can be seen in patients with inherited arrhyth-
Ebstein anomaly, corrected transposition of mias (long QT syndrome, Brugada
the great arteries (TGA). syndrome).
• Presentation is an incidental finding on an
ECG or with suspected or documented SVT.
• Asymptomatic (most common)
• If the accessory pathway can conduct elec-
• Exercise intolerance/fatigue
tricity in a bidirectional fashion (both from
• Syncope/seizure
the atrium to the ventricle and from the ven-
tricle to the atrium), then patients can have ECG
episodes of SVT. • Sinus or junctional bradycardia ± sinus
• If the accessory pathway is robust (i.e., can pauses.
conduct electricity from the atrium to the • Long periods of inactivity in the atrium (i.e.,
ventricle at very fast atrial rates), then patients sinus bradycardia or sinus pauses) can cause
are at risk of sudden death (via rapidly con- disorganization of rhythm and induce
ducted atrial fibrillation leading to ventricular tachyarrhythmias such as atrial fibrillation/
fibrillation). flutter.
ECG Management
• Shortened PR interval • Patients suspected of having SSS should be
• Slurring and slow rise of the initial upstroke referred to a cardiologist for evaluation and
of the QRS complex (delta wave) assessment of need for pacemaker
656 G. Kung et al.
Premature Ventricular Contractions Causes

(PVCs) • Acquired long QT:
–– Drugs (e.g., tricyclic antidepressants, anti-
Background microbials, antiarrhythmics)
• Ectopic beats originating from the ventricle –– Electrolyte disturbances (hypocalcemia,
• Occurs commonly in healthy, normal hearts hypomagnesemia, hypokalemia)
• Can occur with electrolyte disturbances –– Hypothermia
• Can rarely be a presenting sign of myocardi- • Congenital long QT syndrome (see below)
tis or cardiomyopathy
• Occurs more frequently in patients with struc- Clinical Presentation
tural heart disease and certain inherited • May cause ventricular tachyarrhythmias (tor-
arrhythmias sades de pointes)
• Syncope/seizures
Clinical Presentation • Cardiac arrest/sudden death
• Usually asymptomatic
• Feeling that the “heart skips” and then
resumes with a strong beat Congenital Long QT Syndrome
(LQTS)
ECG
• Premature, wide QRS complex not preceded Background
by a P-wave and often followed by a compen- • Caused by mutations in ion channel genes.
satory pause. • Can be an inherited or a spontaneous mutation.
• Frequent PVCs may occur with every other • Remember that not every patient who has a
beat (bigeminy) or every third beat prolonged QTc has congenital LQTS.
(trigeminy). • There exist many different types of long QT
syndrome.
Management
• No treatment for PVCs for the following: Clinical Presentation
–– Single, uniform in appearance • Family history of unexplained sudden death.
–– Suppressed by exercise • Previously healthy patient usually presents
–– No evidence of underlying heart disease or with fainting spells or seizures while swim-
family history of sudden death ming, startling from loud noises, or exercis-
ing. Can also present with seizures,
palpitations, or cardiac arrest.
Prolonged QT Interval • As many as 10% have episodes of sudden
cardiac arrest.
Background • Congenital deafness in the family is associ-
• Corrected QT (QTc) = QT / RR. ated with a particularly malignant and rare
• QT interval corrected between 340 and form of hereditary LQTS (Jervell and Lange-
450 ms is normal. Nielsen syndrome).
• QT interval corrected > 450 ms may be abnor-
mal; > 470 is abnormal. ECG
• QTc may be prolonged in normal neonates • Prolonged QTc and abnormal T-wave
< 7 days of age. morphology.
19 Cardiology 657
• Can also see sinus bradycardia. ECG

• Exercise testing can help to evaluate QTc • Bizarre, wide QRS complex (> 120 ms)
response to exercise. tachycardia:
–– Can be monomorphic:
Treatment ◦◦ Most commonly arising from the RV
• Beta-blockers are very effective in preventing outflow tract (RVOT)
cardiac events, particularly in the most com- –– Less commonly polymorphic (multiple
mon type of LQTS (type 1) different morphologies):
• Magnesium or DC cardioversion can treat ◦◦ More likely to be associated with under-
torsades de pointes lying electrical or cardiomyopathic
• Implantable cardioverter-defibrillator (ICD) disease
is highly effective in preventing sudden car- • P-waves may or may not be visible, depend-
diac death in high risk patients ing on the ventricular rate
• Patients should avoid QT-prolonging
medications Management
• Lifestyle modifications (exercise restriction, • Any patient identified as having VT should be
loud noise avoidance, evaluation and treat- assessed immediately for hemodynamic
ment for electrolyte disturbances in the set- instability
ting of illness) • Once clinically stable, he or she will require a
cardiac evaluation, including ECG, echocar-
diography, exercise stress testing, and Holter
Ventricular Tachycardia (VT) monitoring
• May require medications or ablation, depend-
Background ing on the underlying cause of VT
• VT in children is defined as a tachycardia of
at least three successive ventricular beats
• Nonsustained if the rhythm lasts < 30 s and Ventricular Fibrillation (VF)
terminates spontaneously
• Sustained > 30 s, usually requires therapeutic Background
intervention • VF is a rare pediatric cardiac emergency
caused by uncoordinated activity of the car-
Causes diac muscle fibers, resulting in cardiac arrest
• Drugs • The heart quivers rather than contracts; there-
• Electrolyte imbalances fore, pulses are not palpable
• Underlying cardiac disease
• Prior cardiac surgery ECG
• Cardiomyopathy • Bizarre, random waveform without clearly
• Inherited arrhythmia syndromes identifiable P-waves or QRS complexes and a
roaming baseline
• Some patients are asymptomatic Management
• Syncope • Any patient suspected of having VF requires
• Palpitations advanced cardiac life support intervention
• Dyspnea on exertion, fatigue (defibrillation) because circulation ceases
• Congenital or acquired cardiac disease within seconds of onset
658 G. Kung et al.
Atrioventricular Block (AVB) –– Isoproterenol may increase the ventricular

rate
Background –– Permanent pacemaker may be necessary if
• AVB is a sign of impairment of the normal the cause of heart block is not temporary
conduction system (AV node or His-Purkinje
system) ECG Tips
• Sinus tachycardia and sinus bradycardia are
Causes rarely due to a primary cardiac problem
• Idiopathic • Sinus arrhythmia is a normal finding
• Myocarditis • Left superior axis: can be from AV canal
• Lyme disease defect, tricuspid atresia, or ostium primum
• Exposure to maternal lupus antibodies in atrial septal defect (ASD)
utero • Anomalous left coronary artery from pulmo-
• Congenital heart disease (particularly nary artery (ALCAPA): deep Q-wave I and
postoperative) aVL and ↓ voltage V3–V5 ± LAD (left axis
deviation) ± LVH
Types of AV Block • Hypertrophic cardiomyopathy: LVH with
• First-degree heart block: “strain” (T-wave inversions), deep Q-wave
–– PR interval > 95th percentile for age and V3–V6, left atrial enlargement (LAE)
heart rate (typically > 200 ms) • Right bundle branch block (RBBB):
• Second-degree heart block: –– More common in children particularly
–– Mobitz I—Wenckebach: after open heart surgery
◦◦ Progressive prolongation of PR interval –– Wide QRS (> 120 ms)
until there is a dropped beat –– rSR’ (rabbit ears) in V1 and wide S-wave
–– Mobitz II—normal, stable PR interval, but in V6
periodically there is 1 (or more) dropped • Left bundle branch block (LBBB):
QRS –– Rare in children
• Third-degree heart block: –– Wide QRS (> 120 ms)
–– No conduction through the AV node –– rSR’ notched or slurred in the lateral leads
–– P and QRS have independent but regular I, aVL, and V6
(fixed) rates with a faster atrial (P-wave) –– SRS’ in V1
rate than ventricular (QRS) rate
FETAL PHYSIOLOGY
Management of Heart Block (FIG. 19.13) [1]
• First-degree and second-degree Mobitz I:
depends on cause. If idiopathic and asymp- • Fetal cardiac output is defined as a combined
tomatic, it can be observed cardiac output (CCO) and is directly propor-
• Second-degree Mobitz II and complete heart tional to heart rate, contractility, and preload:
block: –– Fetus is less able to increase its CCO
–– Temporary transcutaneous or transvenous –– HR operates along the top of the Starling
pacing is the treatment of choice for emer- curve, and fetus has limited reserve with
gency situations caused by AV block stress
–– Atropine administration (0.5–1.0 mg) may • Due to non-inflation of the lungs, the pulmo-
improve AV conduction (although can worsen nary vascular resistance (PVR) is high, and
if block is in the His-Purkinje system) there is little flow to the lungs
19 Cardiology 659
Ascending aorta Branch pulmonary

arteries
Ductus arteriosus
Main pulmonary artery
Superior
vena cava LA
Foramen ovale
Coronary
sinus RA
LV
RV
Saturated
to
Left hepatic vein Unsaturated
Right
hepatic
vein Ductus venosus
Left portal
Right vein
portal
vein
Descending aorta
Liver
Placenta
Main
portal
Inferior vein
vena
cava Umbilical artery
Umbilical
vein
Source: Michael Artman, Lynn Mahony, David F. Teitel

Neonatal Cardiology, Third Edition:
www.accesspediatrics.com
Copyright@McGraw-Hill Education. All rights reserved.
Fetal circulation, showing blood flow patterns throughout the central blood vessels, and cardiac chambers. Poorly oxygenated blood streams through the
right ventricle to the placenta and lower body, and well-oxygenated blood streams through the left ventricle to the heart and brain.
Fig. 19.13 Fetal physiology (From Artman et al. [1], ©McGraw Hill Education, with permission)
• Majority of blood flow out the RV is directed delivering the highly saturated blood to the
R->L across the patent ductus arteriosus brain
(PDA) into the descending aorta • With initiation of ventilation at birth, the PVR
• The patent foramen ovale (PFO) directs the drops
umbilical vein (UV) flow from the ductus • PFO shunts (left to right) L->R with the
venosus, which is highly saturated from increased pulmonary venous return to
the placenta, R->L to flow out the aorta, the LA
660 G. Kung et al.
• PDA eventually shunts L->R as the PVR • Venous hum:

drops and then constricts –– The murmur is caused by blood flowing
• If L->R PDA shunting is noted in utero, down the jugular vein
there’s concern for inadequate antegrade pul- –– Typically, louder in diastole as the atrium
monary blood flow empties
–– Characteristics:
◦◦ Continuous murmur
MURMURS ◦◦ Heard in the infraclavicular region
◦◦ Usually right-sided
Background ◦◦ Best heard sitting or standing
• A murmur is heard in most children at one or ◦◦ Disappears when the patient lies down
more examinations ◦◦ Diagnostic if it disappears when the
• Because most murmurs are innocent (i.e., examiner applies gentle pressure over
normal), it is important to differentiate those the jugular vein
that are a manifestation of cardiac disease
• In general, history and physical examination
permit the caregiver to determine if heart dis- Pathologic Murmurs
ease is present
• Systolic murmurs:
–– Systolic ejection murmurs: crescendo-
Innocent Murmurs decrescendo murmur heard best with the
diaphragm:
• Still’s murmur: ◦◦ Ejection murmurs are generated when
–– Early systolic ejection blood flows through a stenotic area or if
–– Short duration there is relative stenosis from increased
–– Low intensity (grade 1–2/6) flow through a normal area
–– Vibrating (or musical) quality ◦◦ Aortic stenosis (right upper sternal bor-
–– Located at the left lower sternal border, der, RUSB)
non-radiating ◦◦ Pulmonary stenosis (left upper sternal
• Peripheral pulmonary artery stenosis of border)
the newborn: ◦◦ Atrial septal defect (relative stenosis
–– Murmur is related to the acute take-off from increased blood flow through the
angle of the branch pulmonary arteries in pulmonary valve)
the newborn ◦◦ Coarctation of the aorta (left clavicle or
–– A murmur louder in the axillae or back back),
than the anterior chest is highly suggestive • Pansystolic murmurs: murmur of the same
of the diagnosis of peripheral pulmonary intensity throughout systole and heard
artery stenosis of the newborn best with the diaphragm:
–– Characteristics: –– Ventricular septal defect (VSD): high
◦◦ Systolic ejection murmur of low intensity pitched, harsh at the left lower sternal
◦◦ Heard best at the left upper sternal bor- border
der and radiates bilaterally to the axillae –– Mitral regurgitation: low pitched, blowing
and back at the left lower sternal border radiating to
◦◦ Split S2 of normal intensity the left axilla, louder with the patient in
◦◦ Murmur disappears, usually in left lateral decubitus position
3–6 months, when the angles remodel –– Tricuspid regurgitation: low pitched, blow-
overtime with increased pulmonary ing at the left and right lower sternal
blood flow border
19 Cardiology 661
• Diastolic murmurs: • Thrills:

–– Early decrescendo murmur heard best with –– Felt best with the palm of the hand
the diaphragm and loudest at the left mid- –– Aortic stenosis: Suprasternal notch thrill is
sternal border: diagnostic
◦◦ Aortic insufficiency (high pitched) heard –– Aortic or pulmonary stenosis: left mid-
best when the patient is leaning forward sternal border; thrill indicates increased
in expiration severity of stenosis
◦◦ Pulmonary insufficiency (low pitched) –– Ventricular septal defect: left mid- or lower
–– Mid-diastolic rumble heard best with the sternal border; thrill may indicate small,
bell restrictive VSD
◦◦ Tricuspid stenosis: right lower sternal • Heave:
border –– Indicates RVH or LVH
◦◦ Mitral stenosis: axilla
• Continuous murmur:
–– Heard best with the diaphragm throughout CONGENITAL HEART DEFECTS
systole and through S2 to diastole, but not
necessarily present throughout diastole, A cyanotic Shunt Lesions
similar to a bruit:
◦◦ PDA (left clavicular region) • Left-to-right shunts (ASD, VSD, PDA):
◦◦ Coronary artery fistula (can be heard –– Physiology:
anywhere in the precordium) ◦◦ Shunting from the systemic (aorta) to
• Heart sounds: pulmonary bed
–– S1: heard best at the left lower sternal ◦ ◦ Degree of shunting depends on the bal-
border ance between systemic and pulmonary
–– S2: heard best at the left mid-upper sternal resistances
border; physiologically, splitting occurs ◦◦ Shunting increases as the PVR decreases
because the aortic valve closes prior to the postnatally
pulmonary valve:
◦◦ Split S2 normally widens with
inspiration Cyanotic Lesions
◦◦ Loud S2: anterior aorta
• Right-to-left shunts: Tetralogy of Fallot
◦◦ Loud, single S2: pulmonary hypertension
(TOF), tricuspid atresia (TA), transposition of
◦◦ Fixed split S2: atrial septal defect
the great arteries (TGA), truncus arteriosus,
◦◦ Paradoxically split S2: aortic stenosis
Ebstein anomaly, totally anomalous pulmo-
–– Systolic click:
nary venous return (TAPVR)
◦◦ Aortic or pulmonary valve stenosis (PS):
–– Physiology:
heard best at the left mid-sternal border
◦◦ Central cyanosis due to desaturated
◦◦ Mitral valve prolapse: mid-systolic click
blood entering systemic circulation with
in axilla
cyanosis noted of the tongue and oral
–– S3: heard best with the bell at the left lower
mucous membranes
sternal border, anterior axillary line in
◦◦ Acrocyanosis due to poor circulation in
mid-diastole
extremities due to vasoconstriction;
–– S4: heard best with the bell at the left lower
other parts of the body are not cyanotic
sternal border, anterior axillary line imme-
◦◦ Cyanosis due to congenital heart defect
diately prior to S1
is constant, not significantly improved
–– Rub: irregular, crackling sound not related
by the administration of oxygen;
to heart rate heard best with the diaphragm
improved saturation close to normal is
anywhere in the precordium
662 G. Kung et al.
more likely related to primary pulmo- Ostium Secundum Defect

nary disease • The most common type of ASD, deficiency of
◦◦ Clinical cyanosis depends on hemoglobin the septum primum
and amount of desaturated blood present • Located in the midportion of the atrial septum.
◦◦ Degree of right-to-left shunting will also • Associated syndromes:
depend on the PVR as well as any –– Holt-Oram syndrome
obstruction to pulmonary flow –– Upper limb anomalies (radius)
◦◦ If there’s insufficient antegrade pulmo- • Closure can be performed with transcatheter
nary blood flow, rely on L->R PDA for or surgical approach
additional flow (TOF, tricuspid atresia,
pulmonary atresia) Ostium Primum Defect
◦◦ In TA and TAPVR, mixing of the sys- • Located in the lower portion of the atrial sep-
temic venous return and pulmonary tum adjacent to the AV valves, deficiency of
venous return occurs by default as the the septum secundum:
result of the anatomy, not usually depen- –– May be associated with a cleft mitral valve
dent on PVR and partial AV canal defect
◦◦ Chronic hypoxia results in polycythemia – – If there is an associated inlet VSD and
and clubbing of extremities on exam common AV valve, the defect is known as
◦◦ R->L shunt lesions are at high risk of a complete AV canal (CAVC) defect or
cerebral vascular accidents endocardial cushion defect
–– Associated syndrome: Down syndrome.
–– Closure is not amenable to transcatheter
Obstructive Lesions closure and is performed surgically; it may
include closure of the mitral valve cleft
• Hypoplastic left heart syndrome (HLHS), coarc-
tation, aortic stenosis, pulmonary stenosis: Sinus Venosus Defect
–– Physiology: • Located by the superior vena cava (SVC) and
◦◦ Obstruction to either systemic or pulmo- at the junction of the pulmonary veins and the
nary blood flow, depending on lesion posterior-superior wall of the atrium (supe-
◦◦ If significant obstruction, may need to rior type) or less commonly by the inferior
rely on PDA for either additional sys- vena cava (IVC) to the right atrium (RA)
temic or pulmonary flow junction (inferior type):
–– Superior type often associated with anom-
alous drainage of the right pulmonary veins
LEFT-TO-RIGHT SHUNTS to the SVC
• Closure is performed surgically and usually
Atrial Septal Defect (ASD) includes baffling of right pulmonary veins to
the left atrium
Anatomy
• Communication between right and left atria Description
in various locations (primum, secundum, • Clinical presentation is similar regardless of
sinus venosus, coronary sinus) location of the defect.
• Most often asymptomatic in the pediatric
Physiology population
• Obligate left-to-right shunt due to difference
in atrial compliance; does not depend on Clinical Presentation
PVR, resulting in right-sided volume over- • Mostly asymptomatic; initial presentation
load overtime may be murmur and abnormal CXR or ECG.
19 Cardiology 663
Physical Examination entricular Septal Defect (VSD)

V
• Systolic ejection murmur due to increased
flow across the pulmonary valve (relative pul- • Most common cardiac malformation
monary stenosis) best heard in the left upper
sternal border Anatomy
• Second heart sound is wide with a fixed split • Communication between the right and left
without respiratory variation. ventricles, various locations (perimembra-
• Mid-diastolic rumble murmur can be heard at nous, muscular, inlet, outlet)
the left lower sternal border due to increased • Muscular type is located in the trabecular
flow across the tricuspid valve (relative tri- midportion of the LV or the apex and may be
cuspid stenosis) single or multiple type (Swiss cheese
septum)
CXR • Outlet (conoseptal, supracristal, subpulmonic)
• Varying degrees of right atrial and ventricular may be associated with aortic insufficiency.
enlargement • Inlet (AV canal defect).
• Increased pulmonary vascular markings • Can be multiple with a combination of
locations
ECG
• Right axis deviation Physiology
• RV conduction delay with RSR1 pattern in • Degree of left-to-right shunting depends on
lead V1 PVR
• RVH • Large shunt results in left-sided volume load
• Right atrial enlargement and dilated LA and LV
• Left superior axis seen in ostium primum • If there is a pressure difference between the
defect two ventricles > 30 mmHg, the defect is clas-
sified as restrictive; if there is a pressure dif-
Treatment ference between the two ventricles
• Mostly asymptomatic, rarely may need < 30 mmHg, the defect is classified as
Lasix® (furosemide) if there are other comor- nonrestrictive
bidities such as chronic lung disease • Pulmonary hypertension if the VSD is not
restrictive and can result in chronic changes
Indications for Closure and pulmonary vascular disease
• Asymptomatic patients with 2:1 or more left-
to-right shunt and evidence of RV volume Description
overload • Shunting increases as PVR drops overtime,
• Symptomatic patients (rare) which partially determines age of
• Elective closure usually performed between 3 presentation.
and 5 years of life • Heart failure and pulmonary overcirculation
• Early closure indicated if the patient has other develop if there is a large left-to-right shunt
hemodynamically significant lesions or heart and result in LV volume overload
failure symptoms
• Depending on location, can be closed by Physical Examination
transcatheter approach with an ASD device or • Holosystolic murmur, best heard at the left
traditional surgical approach lower sternal border
664 G. Kung et al.
• Increased S2 or single S2 if pulmonary hyper- Indications for Closure

tension is present • Heart failure symptoms with failure to thrive
• LV heave with hyperdynamic precordium refractory to medical therapy
• Systolic ejection murmur at the left upper ster- • Reactive pulmonary hypertension
nal border due to increased flow across the pul-
monary valve (relative pulmonary stenosis) Intervention
• Mid-diastolic rumble in the mitral area heard • Most cases are closed surgically; some mus-
best at the apex due to increased flow across cular VSDs may be amenable to transcatheter
the mitral valve (relative mitral stenosis) with device closure
a large shunt
CXR
• Minimal cardiomegaly and increased pulmo-
Common Atrioventricular Canal
nary vasculature with small shunts Defects (AVCDs)
• Cardiomegaly with prominence of the left
Anatomy
atrium and left ventricle with large shunts
• Failure of development of the endocardial
ECG cushions resulting in a common AV valve,
• LV or biventricular hypertrophy due to LV ostium primum ASD, and inlet VSD
dilation
Physiology
• Left atrial enlargement
• Essentially that of a combined ASD and VSD
• T-wave inversions in the left lateral leads due
with left-to-right shunting as the PVR falls
to LV dilation
• Left superior QRS axis with inlet VSD (simi- Description
lar to CAVC) • Common in trisomy 21, can sometimes be
seen in combination with tetralogy of
Course Fallot.
• Small defects can close spontaneously up to • Does not resolve spontaneously, requires sur-
30–50% gical closure
• Small muscular type more likely to close up • The AV valve tissue may be malformed,
to 80% vs. membranous type, which is up to resulting in valvar regurgitation
35%
• Patients with outlet (conoseptal, supracristal, Clinical Presentation
subpulmonic) are at higher risk to develop • Shunting increases as PVR drops overtime,
aortic valve regurgitation and usually undergo which partially determines age of
surgical closure despite small shunt presentation
• Heart failure and pulmonary overcirculation
Treatment develop if there is a large left-to-right shunt
• Diuretics and results in LV volume overload, tachy-
• Digoxin pnea, and difficulty in feeding
• Afterload reduction with ACE inhibitor to
promote more systemic flow and less pulmo- Physical Examination
nary flow • Active precordium if large shunt
• Nutritional supplementation (higher-calorie • VSD is not pressure restrictive, so murmur
formula, nasogastric feedings) will be of low frequency
19 Cardiology 665
• High-frequency systolic murmur may be system, resulting in low diastolic systemic

present if there is significant valvar pressure.
regurgitation • Tissue is responsive to high overall partial
• Mid-diastolic rumble in the mitral area heard pressure of oxygen (PO2)
best at the apex due to increased flow across
the mitral valve (relative mitral stenosis) with Description
a large shunt • Common in preterm infants, patency as a
result of hypoxia and immaturity, early phar-
CXR macological or surgical intervention usually
• Cardiomegaly with prominence of the not required (except if unable to manage heart
left atrium and left ventricle with large failure), and spontaneous closure occurring in
shunts most instances
• PDA persisting > 1 week in term infant is
ECG very unlikely to close spontaneously or with
• Superior QRS axis pharmacological intervention.
• LV or biventricular hypertrophy due to LV • The wall is deficient in both the mucoid endo-
dilation thelial layer and muscular layer
• Left atrial enlargement
Course • Small PDA is usually asymptomatic.
• Progressive pulmonary overcirculation • Large PDA will result in heart failure due to
• Requires surgical closure in the first year of large left-to-right shunt
life
Physical Examination
Treatment • Continuous machinery murmur in neonate
• Diuretics • Continuous (bruit) in older child, heard best
• Afterload reduction with ACE inhibitor to along the left clavicle
promote more systemic flow and less pulmo- • Wide pulse pressure and bounding peripheral
nary flow pulses
• Nutritional supplementation (higher-calorie • LV heave
formula, nasogastric feedings)
• Indications for earlier surgical intervention CXR
• Heart failure symptoms with failure to thrive • Prominent pulmonary artery, with increased
refractory to medical therapy pulmonary vascular markings
• Cardiomegaly involving the left atrium and
left ventricle
Patent Ductus Arteriosus (PDA)
ECG
Anatomy • LV or biventricular hypertrophy
• Residual finding from normal fetal • Left atrial enlargement
circulation • T-wave inversions in left lateral leads
Physiology Treatment
• Depending on size, may be a significant • Indocin (more effective in premature infants)
left-to-right shunt with left-sided volume
promotes closure
load and diastolic runoff into the pulmonary • Diuretics
666 G. Kung et al.
• Nutritional supplementation (higher-calorie • Extreme RVOT obstruction can result in pul-

formula, nasogastric feedings) monary atresia, and these patients are depen-
dent on the PDA or aortopulmonary
Indications for Closure collaterals.
• Heart failure, signs of significant pulmonary
overcirculation refractory to medical Clinical Presentation
management • It depends on degree of RVOT obstruction,
• Reactive pulmonary hypertension. but almost all will have systolic ejection mur-
• Closure is performed transcatheter or surgi- mur at birth.
cally, depending on PDA size and patient • Cyanosis at birth if there’s severe RVOT
size obstruction
• Paroxysmal hypercyanotic attack (or “blue”
or “tet” spell)
RIGHT-TO-LEFT SHUNT • Older unrepaired children may squat to pre-
vent a spell
LESIONS
Physical Examination
Tetralogy of Fallot • Systolic ejection murmur along the left upper
sternal border due to RVOT obstruction.
Anatomy
• Systolic ejection murmur may radiate to the
• Abnormal deviation of the conal septum that
axillae and back as in peripheral pulmonary
results in RVOT obstruction, VSD, overriding
stenosis
aorta, and RVH
• RV heave
Physiology • Continuous murmur of PDA or aortopulmo-
• The degree of RVOT obstruction will deter- nary collaterals (heard best in the back)
mine if and how much R->L shunting will
Associated Syndrome
occur across the VSD
• 22q11.2 deletion (DiGeorge syndrome)
Description
CXR
• Constellation of findings that are the result of
• Boot-shaped heart (cœur en sabot) due to
abnormal development of the conotruncal
upturned RV apex
area in fetal life
• Decreased pulmonary blood flow
• Tetralogy:
• Absent main pulmonary artery segment
–– Multiple levels of RVOT obstruction:
• Possible associated right aortic arch
infundibular, valvar, and supravalvar
–– VSD due to anterior deviation of the conal ECG
septum • Right axis deviation
–– Aortic override of the ventricular septum • RVH
due to anterior deviation of the conal
septum Treatment
–– RVH due to the RVOT obstruction • Neonates with severe obstruction maintain on
• Spectrum of presentation depending on the prostaglandin E1 (PGE) infusion until
degree of RVOT obstruction, from those intervention
without much obstruction and minimal to no • Surgical correction electively within the first
R->L shunting (pink tet) to severe cyanosis year of life
due to extreme RVOT obstruction. • Hypercyanotic spells:
19 Cardiology 667
–– Calming behavior (mother, pacifier, quiet Clinical Presentation

room) • Presents with cyanosis in the newborn period
–– Knee-chest position
–– Squatting if older child Physical exam
–– Oxygen • Single S1; if pulmonary atresia, single S2 as
–– Fluid resuscitation well
–– Morphine • If murmur is present, usually related to VSD/
–– Sodium bicarbonate PS
–– Phenylephrine
–– Esmolol CXR
• Normal cardiac size
Surgery • Small pulmonary artery prominence if there’s
• Some patients can have a palliative aortopul- decreased pulmonary flow
monary shunt (modified Blalock-Taussig
shunt) in infancy until full repair. ECG
• Surgical repair eventually with closure of • QRS with left axis deviation
VSD and resection of sub-pulmonic muscle • Diminished RV forces
and opening of pulmonary valve (PV) as
Treatment
needed; in cases of pulmonary atresia, will
• Initiation of PGE if there’s inadequate pul-
need PV replacement.
monary blood flow and then aortopulmonary
• PV replacement often necessary in the third
shunt
to fourth decade of life.
• Single-ventricle palliation with Glenn and
Fontan procedures
Tricuspid Atresia
Anatomy Transposition of Great Arteries
• Abnormal development of the tricuspid valve
Anatomy
without patency
• Abnormal conoseptal development results in
Physiology the aorta arising from the RV and the pulmo-
• Obligate right-to-left shunt across the atrial nary artery arising from the LV.
septum
Physiology
• Varying degrees of antegrade pulmonary
• Parallel circulations result in desaturated sys-
blood flow, depending on presence and size
temic venous blood being recirculated into
of an associated VSD
the systemic circulation.
Description
Description
• Classified by presence of VSD/pulmonary
• Presents with cyanosis in the neonatal
valve stenosis (PS) and relationship of great
period.
arteries
• Associated VSD in 20% of cases.
• If no VSD with antegrade blood flow, will be
• Atrial-level shunt allows for oxygenated
dependent on PDA flow from the aorta to the
blood to flow to the systemic circulation.
pulmonary artery
668 G. Kung et al.
Clinical Presentation Physiology

• Severe hypoxemia immediately after birth if • Cyanosis due to atrial-level R->L shunting if
there’s inadequate atrial mixing. there’s severe tricuspid regurgitation and/or
• Cyanosis and tachypnea within the first few inadequate antegrade pulmonary blood flow.
days of life once the ductus begins to close: • Worsening tricuspid regurgitation can result
–– Preductal saturation (right hand) may be in right-sided heart failure.
lower than post-ductal saturation (foot) if
pulmonary hypertension is present due to Description
R->L shunting through the PDA. • Malformation of the tricuspid valve charac-
• Hypoxemia is severe despite the oxygen terized by failure of the tricuspid valve appa-
therapy. ratus to separate from the RV myocardium:
–– Displacement of the tricuspid valve annu-
Physical Examination lus into the RV body and tricuspid
• Parasternal heave may be present. insufficiency
• Single and loud second heart sound with –– Atrialization of a portion of the right
occasional split. ventricle
• Murmur is usually absent, or soft ejection mur- –– Massive dilation of the right atrium
mur may be noted at the mid-left sternal border. –– Atrial septal defect or PFO
CXR Clinical Presentation

• Narrow mediastinum with small heart tipped • Newborn with severe form may have marked
on the side (“egg-on-a-string”) due to abnor- cyanosis and massive cardiomegaly, may
mally related great arteries have inadequate pulmonary blood flow, and
• Normal pulmonary vascular markings may be PDA/PGE dependent.
• Cyanosis: Right-to-left shunting through the
ECG PFO because of severe tricuspid insufficiency
• Often normal for a newborn with RVH and causes elevated right atrial pressures.
right axis deviation • Atrial arrhythmias are common because of
atrial enlargement and associated WPW.
Treatment • Sudden death can occur from the
• If transposition is suspected in a newborn, arrhythmias.
start PGE.
• If cyanosis is severe, balloon atrial septos- Physical Examination
tomy is performed to improve mixing between • Holosystolic murmur in the tricuspid area
the left and right sides of the heart. • Widely split S2
• Arterial switch procedure is the surgical pro- • Multiple systolic clicks
cedure of choice and performed within the • Jugular venous distension
first 2 weeks of life. • Enlarged liver
• Long-term survivors of early atrial switch oper- • Cyanosis
ation may have RV failure and/or arrhythmias.
CXR
• Varies from normal to massive box-shaped
Ebstein Anomaly heart (cardiomegaly caused by enlargement
of the right atrium and ventricle)
Anatomy
• Abnormal delamination of the septal leaflet ECG
of the tricuspid valve results in deformity and • Right atrial enlargement
varying degrees of tricuspid regurgitation. • Incomplete right bundle branch block
19 Cardiology 669
• Unusual late QRS configuration Physical Examination

• Accessory pathways (WPW) with short PR • Systolic ejection murmur in the outflow
interval and delta wave region
• Wide pulse pressure
Indications for Treatment • Hyperdynamic precordium
• Cyanosis limiting activity • Aortic insufficiency
• Heart failure • Multiple valve clicks in systole
• Arrhythmias
Associated Syndrome
Treatment • 22q11.2 deletion
• Tricuspid valve repair or replacement
• Neonates: closure of the tricuspid valve with CXR
placement of an aortopulmonary shunt and • Right, left, or combined ventricular hypertro-
conversion to a single-ventricle physiology phy, prominent shadow of the ascending aorta
and aortic knob, increased pulmonary vascu-
larity in the first week of life
Truncus Arteriosus
ECG
Anatomy • Often normal
• Embryological remnant of common arterial
trunk arising from both the right and left Treatment
ventricle. • Heart failure treatment.
• Malaligned VSD. • Early surgical correction due to high risk of
• Pulmonary arteries arise from the truncus as a pulmonary vascular disease in infancy:
main pulmonary artery or as separate right –– Closure of the VSD
and left pulmonary arteries –– Separation of the pulmonary arteries from
• Truncal valve may have 3 to 6 leaflets and the truncus with placement of a conduit or
may be stenotic and regurgitant. patch to connect pulmonary arteries to the
right ventricle
Physiology • Repaired patients require reintervention for
• Due to common outlet, there is intracardiac the RV to pulmonary artery connection, pul-
mixing of desaturated systemic venous blood monary artery stenosis, or truncal valve
with oxygenated pulmonary venous blood. insufficiency.
• As PVR falls, left-to-right shunting increases.
• As shunting increases, overall saturations
will increase. Totally Anomalous Pulmonary
Venous Return (TAPVR)
Description
• Single arterial trunk supplying systemic, pul- Anatomy
monary, and coronary circulation • Pulmonary veins drain to the common conflu-
ence, which does not communicate with the
Clinical Presentation left atrium.
• Cyanosis • Remnant of the primitive vessel remains to
• Murmur serve as a site of egress from the confluence
• Heart failure to various sites.
670 G. Kung et al.
Physiology CXR
• All the pulmonary venous return eventually • Obstructed veins: small heart with ground-
returns to and mixes with the blood in the glass appearance to lung markings
RA. • Supracardiac veins: large supracardiac
• Obligate right-to-left shunt across ASD for shadow (snowman appearance) due to dilated
systemic perfusion. SVC
• If obstruction is noted, symptoms will vary
depending on degree of obstruction. ECG
• If there’s severe obstruction, this results in • RVH
severe hypoxemia and decreased cardiac out- • Peaked T-waves
put due to pulmonary venous congestion and
lack of egress from the lungs to the body. Treatment
• Obstructed TAPVR is a surgical emergency,
Description with PGE usually ineffective.
• Types of TAPVR connections: • Other forms require surgical correction in
–– Supracardiac 50%: infancy.
◦◦ Vertical vein to the left SVC
◦◦ Right SVC
–– Coronary sinus or directly to the right OBSTRUCTIVE LESIONS
atrium 25%
–– Infracardiac 20%, obstruction of the veins Pulmonary Valve Stenosis (PS)
presenting 90–100% of these cases
–– Mixed 5% Anatomy
• Abnormal pulmonary valve leaflets, may be
Clinical Presentation fused and dysplastic
• Cyanosis
• No pulmonary venous obstruction: Physiology
–– No pulmonary hypertension and cyanosis • Limits pulmonary blood flow, can be critical
absent or mild or minor
–– Murmur of pulmonary stenosis
• Mild-to-moderate obstruction: Description
–– Infants can be severely ill because of pul- • Critical pulmonary stenosis of the newborn:
monary hypertension. –– Inadequate antegrade pulmonary blood
–– Tachypnea due to pulmonary edema from flow because of severe stenosis.
pulmonary venous congestion. –– PDA supplies pulmonary blood flow.
–– Cyanosis is mild. –– Right-to-left shunt through the atrial septal
• Severe obstruction: defect, which may result in cyanosis.
–– Cyanosis and tachypnea may be promi- • Valvar pulmonary stenosis:
nent without murmur if there’s severe –– Often asymptomatic
obstruction, especially in the infracardiac • Associated syndromes:
group. –– Noonan syndrome
–– Severe hypoxemia with decreased cardiac –– Williams syndrome
output in the immediate neonatal period. • If gradient < 30 mmHg, not likely to progress
19 Cardiology 671
Physical Examination Clinical Presentation

• Harsh systolic ejection murmur in the pul- • Most patients are asymptomatic and usually
monic area (left upper sternal border). just present with a murmur.
• Thrill may be present in severe stenosis.
• Valve click can be heard at the left mid-ster- Physical Exam
nal border. • Systolic ejection murmur best heard in the
• S2 may be soft in severe stenosis. axillae and across the precordium and can
• RV lift present in severe stenosis. radiate to the back
CXR Associated Syndromes

• Prominent main pulmonary artery • Williams syndrome
• Diminished pulmonary vascular markings • Alagille syndrome
(newborn with critical PS) • Noonan syndrome
ECG Treatment
• Right axis deviation • Benign PPS of the newborn resolves sponta-
• RVH neously usually by 1 year of life.
• May occur unilaterally on the left side once
Treatment PDA closes due to constriction from ductal
• Relief of obstruction by transcatheter balloon tissue around the left pulmonary artery.
dilation or surgical valvotomy. • Syndromic patient may require balloon val-
• Pulmonary insufficiency following treatment vuloplasty or stenting if there’s evidence of
may require intervention later in life. RV hypertension.
Indication for Intervention
• Cyanosis and inadequate antegrade pulmo-
nary blood flow ortic Stenosis
A
• Significant RVH or compromised function
Anatomy
• Estimated RV to PA gradient > 50 mmHg
• Abnormal formation of aortic valve cusps,
can be trileaflet with fusion of two cusps,
bicuspid, or unicuspid/dysplastic
Peripheral Pulmonary Stenosis (PPS)
Anatomy Physiology
• Single or multiple stenosis anywhere along • Varying degrees of stenosis, the most severe
the major branches of the pulmonary artery resulting in decreased cardiac output.
• Sudden death is significant in severe obstruc-
Physiology tion, during or immediately after exercise due
• Depending on severity of stenosis, may result to poor cardiac output.
in increased RV pressures
Description
Description • Types of aortic stenosis:
• PPS associated with syndrome or presenting –– Valvar aortic stenosis occurs due to fusion
later in life may require balloon angioplasty of the valve commissures or malformation
or surgical intervention. of the valve leaflets and is more common in
• Mild PPS is a normal finding in newborns and patients with a bicuspid or unicuspid aortic
resolves spontaneously. valve.
672 G. Kung et al.
–– Bicuspid aortic valve is one of the most –– Chest pain

common congenital heart lesions identified –– Dizziness or syncope with exercise
in up to 2% of adults with aortic stenosis • Sudden death has been reported in children
and is usually asymptomatic in childhood with aortic stenosis.
–– Subvalvar stenosis is due to abnormal
ingrowth of tissue in the left valve outflow Physical Examination
tract (LVOT) separate from the valve but • Systolic ejection murmur loudest in the aortic
may be adherent to the valve: area (right upper sternal border, RUSB), radi-
◦◦ Associated with other congenital heart ating to the carotids.
defects • Subaortic stenosis murmur may be loudest at
◦◦ Can be discovered after correction of the left mid-sternal border.
other anomalies • Thrill in the suprasternal notch.
◦◦ In childhood, may progress rapidly in • Valve click at the left mid-sternal border.
severity and may recur even after surgi- • Soft S2.
cal resection • LV heave.
◦◦ Can lead to concomitant aortic • If there’s associated aortic insufficiency, can
insufficiency have early diastolic murmur.
–– Supravalvar aortic stenosis is the least
common type, associated with Williams CXR
syndrome. • Prominent ascending aorta
• Aortic stenosis is a progressive disease and • Normal size of the heart or cardiomegaly
can be associated with other left-sided
ECG
obstructive lesions such as mitral stenosis,
• LVH and strain
coarctation of the aorta, and interrupted aortic
• Inverted T-wave in the left precordial leads
arch (IAA).
• VSD is a common association when there is Indications for Treatment
an associated arch anomaly. • Symptoms
• LVH
Associated Syndromes
• Estimated peak systolic gradient > 60 mmHg
• Williams syndrome (supravalvar aortic
by echo
stenosis)
• Systolic gradient > 40 mmHg by direct cath-
• Turner syndrome (bicuspid aortic valve)
eter measurement
Clinical Presentation • For subaortic stenosis, associated aortic
• Critical aortic stenosis of the newborn: insufficiency
–– Inadequate flow across the aortic valve
Treatment
leading to decreased cardiac output.
• For neonatal critical aortic stenosis, initiation
–– PDA is needed to maintain blood flow to
of PGE to maintain cardiac output and then
the body from R->L shunting.
balloon valvuloplasty of the aortic valve
–– LV failure can occur.
• Surgical valvotomy
–– Heart failure symptoms.
• Aortic valve replacement (artificial or tissue
• Valvar aortic stenosis in older child:
valve, Ross procedure)
–– Often asymptomatic
• High rate of reintervention, particularly in
–– Murmur
neonates with critical aortic stenosis
19 Cardiology 673
Coarctation of the Aorta • Differential blood pressures between the right

arm and leg (right arm blood pressure
Anatomy > 10 mmHg higher than the leg).
• Discrete or diffuse narrowing of portions of • Radial-femoral delay is a very important sign.
the aortic arch • Systolic murmur is usually heard in the third
and fourth intercostal spaces along the left
Physiology sternal border and can be heard to the infra-
• Results in compromised blood flow to the scapular area and occasionally to the neck.
areas distal to the obstruction and elevated • Continuous murmur may be heard to the back if
pressures proximally there are intercostal collateral vessels present.
Description Associated Syndromes

• Narrowing of the aorta of varying degrees • Turner syndrome (the most common lesion
may occur at any point from the transverse associated with Turner syndrome is bicuspid
arch to the iliac bifurcation. aortic valve)
• 98% of instances occur just below the left • PHACE syndrome (face and heart) (posterior
subclavian artery at the origin of ductus fossa anomalies, facial hemangioma, arterial
arteriosus (juxta-ductal coarctation). anomalies, cardiac anomalies, aortic coarcta-
• Association with berry aneurysm and hyper- tion, eye anomalies): may have stroke
tension may cause cerebrovascular • DiGeorge syndrome in cases with IAA, which
accidents. also has a high association with a concomi-
• Severe cases result in interrupted aortic arch tant VSD
(IAA).
CXR
Clinical Presentations • Cardiomegaly and pulmonary congestion in
• Neonates (critical coarctation): infants with severe coarctation.
–– Flow to the descending aorta is • Enlarged left subclavian artery produces a
inadequate. prominent shadow in the left superior medi-
–– Rapidly symptomatic as soon as the PDA astinum (E sign).
closes. • Notching of the superior border of the ribs in
–– Lower body hypoperfusion. late adolescent due to intercostal collateral
–– Shock/metabolic acidosis. vessels.
–– Severe heart failure.
• Older children: ECG
–– Asymptomatic. • May be normal in young children and mild
–– Present with hypertension noted in upper cases.
extremity. • Older patients may show LVH.
–– Children and adolescents may complain
about weakness or pain in legs after Indications for Treatment
exercise. • PDA dependency
• Hypertension
Physical Examination (in the Absence of PDA) • LVH
• Diminished femoral pulses. • Gradient between arm and leg > 20 mmHg
674 G. Kung et al.
Treatment Physical Examination

• In neonates with critical coarctation, initia- • Murmur of tricuspid insufficiency may be
tion of PGE to reopen the PDA and then present.
surgery. • Flow murmur of increased volume across the
• Transcatheter balloon angioplasty or stent pulmonary valve may be present.
placement in older children. • Poor peripheral perfusion if PDA is closing.
• Surgical excision is not amenable to trans-
catheter intervention. CXR
• Rebound hypertension in the immediate post- • Cardiomegaly
operative period and late after repair can • Increased pulmonary vascular markings
occur.
• Re-coarctation at the site of repair that can be ECG
treated with balloon angioplasty, stent, or • Diminished left-sided forces
surgery.
Treatment
• PGE to maintain PDA
Hypoplastic Left Heart Syndrome • Staged palliation (Norwood or hybrid, bidi-
rectional Glenn, Fontan procedure)
(HLHS)
Anatomy
• Underdevelopment of the mitral valve, LV, C ARDIOVASCULAR GENETICS
and aortic valve
• Chromosomal abnormalities associated with
• Spectrum of severe mitral stenosis with aortic
congenital heart disease:
atresia to mitral/aortic atresia, all with small
–– Trisomy 21: AV canal, VSD, ASD
LV
–– Trisomy 18: VSD, PDA, PS
• Associated aortic arch hypoplasia and
–– Trisomy 13: VSD, PDA
coarctation
–– Wolf-Hirschhorn syndrome: ASD, VSD,
Physiology PDA
• Obligate left-to-right shunt across ASD as –– Cri-du-chat syndrome: VSD, PDA, ASD
egress from the left atrium –– Turner syndrome: coarctation, aortic ste-
• No aortic antegrade flow, depends on R->L nosis, ASD
shunting across PDA for systemic perfusion • Microdeletion syndromes associated with
cardiac disease:
Description –– 22q11 deletion (DiGeorge): tetralogy of
• PDA dependent for systemic perfusion, may Fallot, interrupted aortic arch, truncus arte-
not present until PDA starts to close riosus, aortic arch anomalies
–– Williams syndrome: supravalvar aortic ste-
Clinical Presentation nosis, supravalvar pulmonic stenosis
• Cyanosis –– Single-gene disorders:
• Tachypnea ◦◦ Marfan syndrome: aortic root dilation,
• Circulatory shock when the PDA closes mitral valve prolapse
• Heart failure ◦◦ Holt-Oram syndrome: ASD, VSD
19 Cardiology 675
◦◦ Noonan syndrome: pulmonary stenosis, Diagnosis

hypertrophic cardiomyopathy, ASD, • Evidence of a preceding GAS infection along
partial AV canal, coarctation with the presence of two major manifesta-
◦◦ Tuberous sclerosis: cardiac tions or one major and two minor
rhabdomyomas manifestations
◦◦ Cornelia de Lange syndrome: VSD • Streptococcal antibodies: antistreptolysin O
◦◦ Alagille syndrome: branch pulmonary (ASO), antihyaluronidase (AHase), and anti-
artery stenosis deoxyribonuclease B (anti-DNase B)
antibodies
INFECTION/VASCULITIS Treatment of ARF

• Aspirin 80–100 mg/kg/day, continued until
Acute Rheumatic Fever (ARF) all symptoms have resolved.
• Restricted activity/bed rest.
Background • Carditis is managed with therapies used for
• ARF is caused by previous group A strepto- heart failure.
coccal (GAS) pharyngeal infection. • Corticosteroids are used if carditis is severe.
• Due to immune-mediated inflammatory • Eradication of GAS requires the same antibi-
response to the infection. otic regimens that are used to treat GAS
• Most common among children aged pharyngitis.
5–15 years. • Household contacts should have throat cul-
ture and if positive for GAS should be treated.
Classified according to the Jones Criteria • Prophylactic antibiotics should be started
(2015) [2] immediately after the therapeutic antibiotic
• Evidence of recent GAS infection: course is complete:
–– Positive throat culture or rapid strep test. –– Penicillin VK, sulfadiazine (or macrolides
–– Elevated or rising antistreptococcal anti- if allergic) for patients at lower risk of ARF
body titer. recurrence.
–– Initial diagnosis requires 2 major or 1 –– Benzathine penicillin G intramuscularly
major and 2 minor. every 4 weeks for patients at higher risk of
–– Recurrent diagnosis requires same as ini- ARF recurrence.
tial or 3 minors. –– Prophylaxis should continue for several
• Minor criteria: years, typically until a patient is an adult
–– Fever ≥ 38.5 °C and recurrence-free for 10 years.
–– Polyarthralgia –– Longer prophylaxis is indicated if the
–– Erythrocyte sedimentation rate (ESR) patient has residual heart disease.
≥ 60 mm/h and/or C-reactive protein
(CRP) ≥ 3 mg/dL
–– Prolonged PR interval awasaki Disease (KD) [3]
K
• Major criteria:
–– Polyarthritis Background
–– Carditis • Kawasaki disease is an acute vasculitis of
–– Erythema marginatum childhood that leads to coronary artery aneu-
–– Subcutaneous nodules rysms in ~25% of untreated cases.
–– Sydenham chorea
676 G. Kung et al.
• It is the most common cause of acquired heart –– Musculoskeletal:

disease in children in developed countries. ◦◦ Arthritis, arthralgia (pleocytosis of syno-
• The etiology of KD is unknown, but it occurs vial fluid)
more commonly in winter and early spring in –– Gastrointestinal:
North America. ◦◦ Diarrhea, vomiting, abdominal pain
• Ratio of males to females is 1.5:1, with high- ◦◦ Hepatitis, jaundice
est relative risk in Asian children. ◦◦ Gallbladder hydrops
• KD occurs most frequently in children ◦◦ Pancreatitis
< 5 years of age. –– Nervous system:
◦◦ Extreme irritability
Clinical Presentation ◦◦ Aseptic meningitis (pleocytosis of cere-
Classic KD brospinal fluid)
• Presence of fever for at least 5 days (day of ◦◦ Facial nerve palsy
fever onset is the first day), with at least 4 of ◦◦ Sensorineural hearing loss
the 5 following principal clinical features: –– Genitourinary:
1. Erythema and cracking of lips, strawberry ◦◦ Urethritis/meatitis, hydrocele
tongue, and/or erythema of the oral and ◦◦ Others
pharyngeal mucosa ◦◦ Desquamating rash in the groin
2.
Bilateral bulbar conjunctival injection ◦◦ Retropharyngeal phlegmon
without exudate ◦◦ Anterior uveitis by slit lamp
3. Rash: maculopapular, diffuse erythroder- examination
mal, or erythema multiforme-like
Incomplete KD
4. Erythema and edema of the hands and feet
• A challenging subset of patients who do not
in acute phase and/or periungual desqua-
meet the classic criteria of KD:
mation in subacute phase
–– Children with fevers ≥ 5 days and 2 or 3
5. Cervical lymphadenopathy (≥ 1.5 cm

compatible clinical criteria
diameter), usually unilateral
–– Infants with fevers ≥ 7 days without other
• Patients who lack full clinical features of
explanations
classic KD may have incomplete KD.
• More common in infants and older children
• If coronary abnormalities are detected, the
• Important considerations:
diagnosis of KD is considered confirmed.
–– Recommended: Infants younger than age
• Other clinical findings:
6 months who have had ≥ 7 days of fever
–– Cardiovascular:
of unclear etiology and elevated inflamma-
◦◦ Myocarditis, pericarditis, valvular regur-
tory markers undergo echocardiography.
gitation, shock
–– Clinicians should not dismiss the diagno-
◦◦ Coronary artery abnormalities
sis of KD in children who have symp-
◦◦ Aneurysms of medium-sized noncoro-
toms that are attributed commonly to
nary arteries
viral illnesses.
◦◦ Peripheral gangrene
–– Coronary artery dilatation is generally not
◦◦ Aortic root enlargement
detected by echocardiography until after
–– Respiratory:
the first week of illness, and a normal echo-
◦◦ Peribronchial and interstitial infiltrates
cardiogram in the first week of illness does
on CXR
not rule out the diagnosis of KD.
◦◦ Pulmonary nodules
19 Cardiology 677
Laboratory Studies Treatment

• Laboratory tests are nonspecific but provide • Once the diagnosis of KD is confirmed, treat-
support for a diagnosis of KD in patients with ment with high-dose intravenous immuno-
suggestive but incomplete features. They are globulin (IVIG) (2 g/kg) should be instituted
listed here in order of frequency of promptly and continued until the patient is
occurrence: afebrile for 48 h. Treatment is administered
–– Erythrocyte sedimentation rate (ESR) within the first 10 days of illness onset but as
≥ 40 mm/h (in most cases of KD) soon as possible after diagnosis.
–– Serum C-reactive protein (CRP) ≥ 3 mg/ • Treatment with IVIG after day 10 of illness is
dL (in most cases of KD) reserved for those with ongoing fever and
–– Platelet count of ≥ 450,000/mm3 after the evidence of systemic inflammation on labora-
seventh day of fever (in most cases of KD) tory studies.
–– White blood cell count (WBC) ≥ 15,000/ • Administration of high-dose aspirin (80–
mm (occurs commonly in KD)
3
100 mg/kg/day) is reasonable until the patient
–– Anemia (occurs commonly in KD) is afebrile, although there is no evidence that
–– Albumin ≤ 3 g/dL (occurs commonly in this reduces coronary artery aneurysms.
KD and is associated with a more severe • This may be changed to low-dose aspirin
and prolonged clinical course) (3–5 mg/kg/day) once the child has been afe-
–– Urine 10 ≥ WBC/hpf (occurs in 80% of brile for 48–72 h.
KD) • Low-dose aspirin is administered until
–– Elevated transaminases or gamma-glu- 6–8 weeks after onset of illness and can then
tamyl transpeptidase (occurs in 40–60% of be discontinued if the echocardiographic
KD) findings are normal.
–– Hyperbilirubinemia (occurs in 10% of KD) • Therapies used in IVIG resistance include
corticosteroids or infliximab (a tumor necro-
Echocardiography sis factor inhibitor).
• Echocardiographic findings include as • Measles and varicella-containing vaccina-
follows: tions are contraindicated for 11 months after
–– Coronary artery abnormalities administration of IVIG.
–– Valvular abnormalities (mitral and aortic
valves) Evaluation of Incomplete KD
–– Aortic root dilation • The American Heart Association (AHA) rec-
–– Myocardial dysfunction or myocarditis ommendations for incomplete KD:
• If the diagnosis is clear, treatment for KD –– If CRP < 3 mg/dL and ESR < 40 mm/h:
should not be withheld while waiting to ◦◦ Continue monitoring (clinical symptoms
schedule or obtain the results of and laboratory assessment) if fevers
echocardiography. persist.
• Echocardiography should be obtained at ◦◦ Echocardiogram if typical peeling
diagnosis, 1–2 weeks later, and 4–6 weeks develops
after treatment. –– If CRP ≥ 3 mg/dL and/or ESR ≥ 40 mm/h:
• Children who have persistent or recrudescent ◦◦ Treat if there are positive echocardio-
fever or who have known coronary artery gram findings or three or more labora-
abnormalities need close follow-up with a tory findings:
pediatric cardiologist. ▪▪ Anemia for age
678 G. Kung et al.
▪▪ Platelet count ≥ 450,000 after seventh

day of fever
▪▪ Albumin ≤ 3 g/dL
▪▪ Elevated alanine transaminase (ALT)
level
▪▪ WBC count of ≥ 15,000/mm3
▪▪ Urine ≥ 10WBC/hpf
• Consultation with a KD expert if needed
Prognosis of KD
• Incidence of coronary artery involvement in
treated children has fallen to less than 5%,
and only 1% of children develop giant coro-
nary aneurysms.
• Long-term prognosis is unclear. Increased
risk of atherosclerotic heart disease in adult-
hood is possible.
Infective Endocarditis (IE)

Background
• The diagnosis can be obvious in the presence
of persistently positive blood cultures with a
Fig. 19.14 Janeway lesions in a patient with infective
predisposing cardiac lesion. endocarditis
• Endocarditis in children is often associated
with the presence of a predisposing cardiac –– Positive echocardiography for vegetation
lesion, an intravascular foreign body (central or new valvular regurgitation
venous catheter, valve prosthesis, intracar- • Minor criteria:
diac device), and/or an immunocompromised –– Predisposition to IE
host. –– Fever
–– Vascular phenomena (arterial emboli, sep-
Clinical Presentation tic pulmonary infarctions, mycotic aneu-
• New regurgitant murmur or heart failure. rysm, intracranial hemorrhage, conjunctival
• Evidence of emboli to the fundi, skin, digits, hemorrhages, Janeway lesions (Fig. 19.14))
or conjunctivae. –– Immunologic phenomena such as glomer-
• Additional organ systems may be affected by ulonephritis, Osler nodes, Roth spots, and
emboli, including the kidneys, spleen, and rheumatoid factor
brain. –– Single positive blood culture or serologic
evidence of active infection with an organ-
The Duke Criteria ism consistent with IE
• Two major/one major and three minor/five
minor criteria Antibiotic Prophylaxis
• Major criteria: • Guidelines limit prophylaxis to cardiac con-
–– Two positive blood cultures at least 12 h ditions that have the highest risk of poor out-
apart come from IE:
19 Cardiology 679
–– Prosthetic heart valves • Can present as chest pain in children.

–– Previous IE • Pericarditis can be accompanied by
–– Unrepaired cyanotic heart disease that myocarditis.
includes palliative shunts and conduits
–– Completely repaired congenital heart dis- Causes
ease with prosthetic material or device dur- • Infection:
ing the first 6 months following the –– Viral is the most common cause in
procedure children.
–– Repaired congenital heart disease with – – Bacterial (staph, tuberculosis).
residual defects at the site or next to the site • Autoimmune disease
of the prosthetic device • Rheumatic fever
–– Valvulopathy in a transplanted heart • Uremia
• Malignancy
Indication for Prophylaxis • Reaction to a drug
• All dental procedures that involve manipula- • After cardiac surgery
tion of gingival tissue or the periapical region • Idiopathic (one-third of the cases have no
of teeth or perforation of the oral mucosa identifiable cause)
• Invasive procedure of the respiratory tract
that involves incision or biopsy of the respira- Clinical Presentation
tory mucosa, such as tonsillectomy or • When viral, patients report a prodrome of
adenoidectomy fever or respiratory or gastrointestinal
• Surgical procedures on infected tissue of skin illness.
or the musculoskeletal system • Chest pain:
–– Substernal, sharp
Prophylactic Antibiotics –– Worse with inspiration
• Ampicillin or first- or second-generation oral –– Relieved by sitting upright and leaning
cephalosporins are recommended in nonaller- forward
gic patients. –– Radiates to the scapular ridge due to irrita-
tion of the phrenic nerves
Treatment
• Antimicrobial therapy for IE should be Physical Examination
administered in a dose designed to provide • Friction rub (pathognomonic finding):
sustained bactericidal serum concentrations –– Scratchy, high pitched, to-and-fro sound
throughout the entire dosing interval. –– Loudest when the patient is upright and
• The minimum inhibitory concentration leaning forward
should be determined for all patients. –– Heard best in the second to fourth intercos-
• The duration of intravenous antimicrobial tal spaces along the left sternal border or
therapy is approximately 4–6 weeks. the mid-clavicular line
• If a large or rapidly developing pericardial
effusion is present, patients can have the
Acute Pericarditis following:
–– Tachycardia
Background –– Pulsus paradoxus
• An inflammatory condition of the –– Muffled heart tones
pericardium.
680 G. Kung et al.
–– Evidence of decreased RV filling (right

atrial collapse, RV free wall compression,
distended systemic veins)
Management
• Identify and, if possible, treat the underlying
cause.
• Pericardiocentesis if there is evidence of
tamponade.
• Symptoms tend to resolve within days for
most patients.
• Ibuprofen is the preferred first-line agent
because it has the lowest incidence of adverse
Fig. 19.15 8-year-old boy presenting with chest pain, effects.
tachycardia, and shortness of breath; chest radiography
shows moderate cardiomegaly suggestive of pericardial effu-
sion. Nonspecific increased central interstitial lung mark-
Complications
ings, presumably viral pneumonitis • Recurrence (most likely with autoimmune
causes)
Diagnosis • Constrictive pericarditis
• Labs may show elevations of the WBC, ESR,
and CRP.
• If there’s myocardial involvement, the C ardiac Tamponade
plasma troponin concentration also may be
increased. Background
• Pericardial effusion rapidly exceeds the peri-
CXR cardial reserve volume:
• Usually appears normal in patients who have –– Effusion can be serous, hemorrhagic, chy-
acute pericarditis. lous, or infectious.
• When a significant pericardial effusion is • Rapidity of accumulation rather than volume
present, the heart may have a triangular shape more likely affects hemodynamics.
with a smooth border, known as a “water bot- • Increases intrapericardial pressure, impairs
tle heart” (Fig. 19.15). cardiac filling, and results in decreased car-
diac output.
ECG
• Diffuse ST segment elevation and PR seg- Clinical Presentation
ment depression • Sudden onset of acute dyspnea/orthopnea
• If associated pericardial effusion: • Tachycardia
–– Low-voltage QRS complex on ECG. • Distant heart sounds
–– Amplitude of the QRS complex returns to • Pulsus paradoxus (PP): > 10-mmHg drop in
normal after the pericardial effusion systolic blood pressure during nonmechani-
resolved or is drained. cal inspiration
• Echocardiography: • If PP is significant, can be palpated on physi-
–– Pericardial effusion cal exam
19 Cardiology 681
CXR Causes
• Water bottle heart • Viral: most common, especially enteroviruses
• New cardiomegaly such as coxsackie B virus
• Bacterial: Streptococcus pyogenes,
ECG Staphylococcus aureus, Mycobacterium
• Electrical alternans: cyclic variation in QRS tuberculosis
caused by excessive motion of the heart • May also be caused by fungi, protozoa, auto-
within a fluid-filled pericardial sac immune diseases
• Decreased voltages
Echocardiogram • Symptoms frequently may follow history of
• Effusion noted in the pericardial space, size flu-like illness (fever, fatigue, malaise).
itself not diagnostic, clinical diagnosis • Symptoms may range from mild to severe
• > 30% variation of mitral valve “E” Doppler and may include the following:
with inspiration, correlates with PP –– Lethargy
• RV/atrial collapse –– Respiratory distress
–– Chest pain
Management –– Gastrointestinal symptoms
• Maintain adequate preload to maintain car- –– Other symptoms of heart failure
diac filling. –– Shock
• Requires an emergent pericardiocentesis, can • Physical exam is variable according to sever-
be done with echo guidance. ity and may include the following:
–– Resting tachycardia (sinus)
–– Tachypnea
Constrictive Pericarditis –– Rales
Background –– Muffled heart sounds or gallop rhythm
• Obliteration of the pericardial space second- –– Hepatomegaly
ary to inflammation. –– Lower extremity edema
• Tuberculosis is the most common cause –– Poor perfusion
worldwide.
CXR
Clinical Presentation • Pulmonary edema.
• Signs and symptoms of right-sided heart • Cardiomegaly may or may not be present.
failure
ECG
• Physical Examination
• Low voltage.
–– Faint friction rub
• ST segment and T-wave abnormalities.
–– Diastolic knock
• Dysrhythmias may be present.
–– Jugular venous distention
• Ischemic changes.
–– Hepatomegaly
Echocardiogram
• Decreased ejection fraction.
Myocarditis • Ventricular dilation may or may not be
present.
Definition
• Pericardial effusion.
• Inflammation of the myocardium
682 G. Kung et al.
Laboratory ◦◦ Truncus arteriosus (TA)

• Elevated troponin and brain natriuretic pep- ◦◦ Totally anomalous pulmonary venous
tide (BNP). connection (TAPVC)
• CRP or ESR may be elevated. –– Valve insufficiency—depending on sever-
• Positive viral studies may be supportive of ity, may present anytime between infancy
myocarditis, although not definitive. to adolescence. Generally, left-sided insuf-
• Definitive diagnostic test is myocardial ficiency will present earlier:
biopsy with polymerase chain reaction (PCR), ◦◦ Tricuspid or pulmonary insufficiency:
although biopsy can be negative because of increased RV volume load
the patchy nature of myocarditis. ◦◦ Mitral or aortic insufficiency: increased
LV volume load
Management –– Obstructive lesions—generally presents in
• Supportive treatment (inotropic agents, the newborn to early infancy period as the
diuretics, afterload-reducing medications). PDA begins to close:
• Evidence for IVIG or corticosteroids is ◦◦ Aortic, pulmonary, and mitral valve
lacking. stenosis
• If medications fail, mechanical support ◦◦ Coarctation of the aorta
(extracorporeal membrane oxygenation ◦◦ Interrupted aortic arch
[ECMO] or ventricular assist device) may be ◦◦ Hypoplastic left heart syndrome (HLHS)
needed. • Other intrinsic heart diseases:
• Heart transplant for refractory heart failure. –– Cardiomyopathies—depending on sever-
ity, may present anytime between infancy
to adolescence:
HEART FAILURE ◦◦ Dilated cardiomyopathy
◦◦ Restrictive cardiomyopathy
Congestive Heart Failure ◦◦ Hypertrophic cardiomyopathy
◦◦ LV noncompaction
Background –– Dysrhythmias—variable timing of presen-
• Definition—cardiac output is insufficient to tation, depending on etiology:
meet the metabolic demands of the body: ◦◦ Supraventricular tachycardia
–– Low cardiac output: decreased stroke vol- ◦◦ Ectopic atrial tachycardia
ume +/- decreased heart rate ◦◦ Atrial flutter/fibrillation with rapid ven-
–– High metabolic demand: increased blood tricular response
volume, increased metabolic rate ◦◦ Inappropriate bradycardia
◦◦ Congenital heart block
Causes • Acquired heart disease—variable timing of
• Congenital heart disease: presentation, depending on etiology.
–– Left-to-right shunt causing excessive pul- Infections may occur at any time. The risks of
monary blood flow—generally presents at anthracycline toxicity and failing Fontan cir-
1–3 months of life when pulmonary vascu- culation increase as the patient gets older:
lar resistance falls to normal: –– Viral myocarditis
◦◦ VSD –– Other cardiac infections (endocarditis,
◦◦ Atrioventricular canal defect (AVCD) pericarditis)
◦◦ PDA –– Pericardial effusion or tamponade
◦◦ Transposition of the great arteries (TGA) –– Anthracycline toxicity
19 Cardiology 683
–– Failing Fontan circulation –– Abdomen: hepatomegaly, ascites, abdomi-

–– Myocardial infarction nal pain
• High metabolic demand (i.e., high-output –– Extremities: peripheral edema, cool
heart failure): extremities, prolonged capillary refill time
–– Septic shock • CXR:
–– Arteriovenous malformations –– Cardiac enlargement
–– Anemia –– Pulmonary congestion
–– Thyrotoxicosis • ECG:
–– Dysrhythmias
–– Atrial enlargement
Clinical Presentation –– Ventricular hypertrophy
• Neonate: –– Right or left bundle branch block
–– Lethargy –– Abnormal repolarization pattern
–– Respiratory distress • Echocardiography:
–– Irritability –– Structural heart disease
–– Shock –– Systolic or diastolic ventricular dysfunction
• Infant: –– Atrial or ventricular dilation
–– Failure to thrive –– Valve regurgitation or stenosis
–– Poor feeding –– Effusions (both pericardial and pleural)
–– Increased fatigability • Laboratory studies:
–– Respiratory distress or tachypnea –– BNP and N-terminal pro-b-type natriuretic
–– Irritability peptide (NT-proBNP)
• Older children: –– Inflammatory markers: CRP, ESR
–– Exercise intolerance –– Markers of cardiac ischemia: troponin
–– Gastrointestinal complaints: abdominal
pain, anorexia, nausea, vomiting Management
–– Respiratory symptoms: cough, wheezing, • Acute:
dyspnea, orthopnea –– Assessment of fluid status and cardiac
–– Weight gain (from fluid accumulation) output:
◦◦ Fluid overload:
Diagnostic Evaluation ▪▪ Diuretics
• Vital signs: ▪▪ Ultrafiltration
–– Desaturation ◦◦ Low cardiac output:
–– Tachycardia ▪▪ Inotropic support (epinephrine, dopa-
–– Tachypnea mine, milrinone)
–– Hypotension ▪▪ Vasodilation and lusitropic support
–– Weight gain or loss (milrinone)
• Potential physical examination findings: ▪▪ Mechanical circulatory support
–– General: discomfort, agitation, cyanosis, ▪▪ ECMO
pallor, diaphoresis, failure to thrive ▪▪ Ventricular assist device
–– Head, eyes, ears, nose, and throat (HEENT): –– Prompt treatment of noncardiac causes of
jugular venous distension heart failure such as the following:
–– Respiratory: tachypnea, rales, grunting, ◦◦ Anemia
retractions ◦◦ Hypo-/hyperthyroidism
–– Cardiovascular: pansystolic mitral regurgi- ◦◦ Sepsis/acidosis
tation murmur, gallop rhythm ◦◦ Infection
684 G. Kung et al.
–– Corrections of structural cardiac • Physical examination:

anomalies: –– Murmur of mitral insufficiency
◦◦ Closure of intracardiac shunts –– S3 gallop
◦◦ Relief of left or right ventricular outflow –– Hepatomegaly
tract obstruction –– Jugular venous distention
◦◦ Relief of valvular regurgitation –– Tachypnea and rales
◦◦ Treatment of cardiac dysrhythmia
–– Cardiac transplantation CXR
• Chronic: • Cardiomegaly
–– Diuretics (typically with a loop diuretic • Pulmonary edema
such as furosemide): relieve signs and
symptoms of volume overload ECG
–– Afterload reduction: • RVH and LVH
◦◦ Angiotensin-converting enzyme • Atrial enlargement
inhibitors • Nonspecific ST segment or T-wave changes
◦◦ Beta-blockers
Echocardiography
◦◦ Angiotensinogen II receptor antagonist
• Dilation of all the chambers and poor
–– Reverse remodeling agents:
contractility
◦◦ Mineralocorticoid receptor antagonist
–– Cardiac glycosides (e.g., digoxin) Treatment
• Treatment of congestive heart failure
• Treatment of the underlying cause
C ARDIOMYOPATHIES • Heart transplant for unresponsive cases
Dilated Cardiomyopathy
Restrictive Cardiomyopathy
Description
• Disease of the myocardium characterized by Description
ventricular dilation and decreased ejection • Disease of the myocardium characterized by
fraction elevated diastolic filling pressures, dilated
right and left atrium, and normal ventricular
Causes size and function
• Idiopathic
Causes
• Familial with different genetic inheritance
• Idiopathic
• Cardiotoxic drugs, e.g., anthracyclines
• Sarcoidosis
• Neuromuscular diseases
• Amyloidosis
• Metabolic/nutritional
• Mucopolysaccharidoses
• Autoimmune disease
• Radiation
• Severe anemia
• Malignancy
• Thyrotoxicosis
• Tachyarrhythmia (supraventricular tachycar- Clinical Presentation
dia, ectopic atrial tachycardia) • Heart failure
• Pulmonary hypertension
Clinical Presentation • Atrial arrhythmias
• Heart failure • Thromboembolism
19 Cardiology 685
CXR • Dizziness
• Mild to moderate atrial enlargement • Physical examination:
–– Double apical impulse
ECG –– S4 gallop
• Biatrial enlargement –– Systolic ejection crescendo-decrescendo
• Nonspecific T-wave abnormalities murmur (best heard at the apex and left
sternal border):
Echocardiography ◦◦ Valsalva maneuver or standing increases
• Atrial enlargement the murmur (due to decrease in the
• Normal LV and RV size and function preload).
◦◦ Murmur decreases with hand grip (due
Management
to increase in afterload) or squatting
• Treatment of heart failure and arrhythmia
(due to increase in the preload).
• Heart transplantation
–– Murmur of mitral insufficiency (holosys-
tolic murmur)
Hypertrophic Cardiomyopathy CXR
(HCM) • Mild cardiac enlargement
• LV and left atrial hypertrophy
Description
• Disease of the myocardium characterized by ECG
increased ventricular wall thickness and mass • LVH
with normal or hyperdynamic ventricular • Inverted T-waves in left leads
function. • Nonspecific T-wave abnormality
• HCM is the most common cardiac cause of
sudden death in adolescents and young adults. Echocardiography
• HCM occurs in 1 out of 500 people (0.2% of • Shows the pattern of hypertrophy
the population). • Shows the flow gradient across the left and
right ventricular outflow tracts
Causes • Diastolic dysfunction
• Genetic disorder:
–– Familial hypertrophic cardiomyopathy is Management
autosomal dominant in 50% of cases. • In symptomatic patients, beta-blocker or cal-
• Idiopathic cium channel blocker may decrease the out-
• Metabolic flow obstruction and improve the symptoms.
• Implantable defibrillator if:
Clinical Presentation –– Aborted cardiac arrest
• Sudden death (the most devastating –– History of ventricular tachycardia
presentation) –– Family history of sudden cardiac death
• Dyspnea (the most common presenting symp- –– Massive hypertrophy (LV wall thickness
tom in adults) ≥ 30 mm)
• Syncope or presyncope • Myomectomy.
• Angina • Heart transplant.
• Palpitation
686 G. Kung et al.
MISCELLANEOUS Diagnoses
• Doppler ultrasound may show occluded
Sudden Cardiac Death SVC and other systemic veins; may be lim-
ited by acoustic windows and location of
• Incidence is ~0.6 to 6/100,000 children in the obstruction.
United States. • Angiography will show occlusion and forma-
• 20 to 25% of sudden cardiac deaths occur tion of collaterals; could have intervention in
during sports. the cardiac catheterization lab for dilation,
• Causes: stenting, and recanalization.
–– Hypertrophic cardiomyopathy (most com-
mon cause)
–– Coronary artery abnormalities Dyslipidemia
–– Marfan syndrome
–– Congenital heart disease Background
–– Myocarditis • Dyslipidemia refers to a pathologic imbal-
–– Inherited arrhythmias (long QT syndrome, ance in the levels of low-density lipoprotein
catecholaminergic polymorphic ventricu- (LDL) cholesterol (LDL-C), high-density
lar tachycardia, Brugada syndrome, etc.) lipoprotein (HDL) cholesterol, and
–– WPW syndrome triglycerides.
–– Ischemic heart disease • It is recognized as a risk factor for adult car-
–– Other cardiomyopathies (dilated, arrhyth- diovascular disease (CVD).
mogenic RV dysplasia) • Elevated cholesterol levels continue into
–– Commotio cordis adulthood.
• Treating childhood dyslipidemia may help
prevent or reduce the risk of adult CVD and
Superior Vena Cava Syndrome reduce the atherosclerotic burden later in life.
Background Screening Target Group (Table 19.1)

• Occurs in the setting of obstructed systemic • Birth to 2 years: no lipid screening.
venous return from the upper body to the • For age 2–8 years: Obtain fasting lipid profile
heart (FLP) only if there’s family history (+) for
• Results in increased central venous pressures early CVD, a parent with dyslipidemia, any
and presents clinically with swelling of the other risk factors (+), or high-risk conditions.
upper extremities, head, or face • For age 9–21 years: Obtain universal lipid
• Can be caused by stenosis or occlusion of the screen between age 9–11 and 17–21 years,
lumen internally by clot (hypercoagulable with nonfasting non-HDL cholesterol (for
state, thromboses from indwelling lines) or age 9–19 years < 145; for age 20–21 < 190),
external compression by a mass or FLP and manage per lipid algorithms as
needed.
Clinical Presentation • Risk stratification and management of chil-
• Swelling and edema of the head and upper dren with conditions predisposing to acceler-
extremities ated atherosclerosis and early CVD
• Prominent venous distention in the same (Table 19.2):
distribution –– Step 1: Risk stratification by disease
• Chylothorax process
19 Cardiology 687
Table 19.1 Screening target groups for dyslipidemia

Recommendations Age < 10 years Age 10–19 years Age 20–21 years
Target TGs TGs < 100, LDL-C < 130 TGs < 130, LDL-C < 130 TGs < 150, LDL-C < 160
Manage as per algorithm TG ≥ 100 < 500, TG ≥ 130 < 500 High levels—manage as per
LDL-C ≥ 130 ≤ 250 LDL-C ≥ 130 ≤ 250 adult treatment panel (ATP III
Consult lipid specialist TGs > 500, LDL-C > 250 TGs > 500, LDL-C > 250 algorithm)
ATP Adenosine triphosphate, LDL-C Low-density lipoprotein cholesterol, TG Triglyceride
Table 19.2 Risk stratification and management of children with conditions predisposing to accelerated atherosclerosis and
early cardiovascular disorders
Risk level Step 1 Step 2 Step 3 Step 4
High 1. DM I and 2 CVD risk factors High-risk cutoffs Intensive lifestyle
management
2. CKD/end-stage renal 1. Family history of early 1. BMI ≤ 85th percentile CHILD 1
disease/post-kidney CVD (♂ ≤ 55 years; ♀ Activity Rx
transplant ≤ 65 years) Weight loss as
needed
3. Post-heart transplant 2. Fasting lipid profile 2. BP < 90th percentile for Condition-specific
4. Kawasaki disease with 3. Smoking history age, sex, and height management
current coronary artery percentile
aneurysms 4. BP (3 separate 3. LDL-C < 120, TG < 90
occasions) for age/sex/ Non-HDL-C < 120
height (percentile)
5. Height, weight, BMI 4. FG < 100, HBA1c < 7%
Moderate 1. Kawasaki disease with 6. Diet, physical activity/ Moderate-risk cutoffs Intensive lifestyle
regressed coronary exercise history management
aneurysms 1. BMI < 90th percentile CHILD 1
2. BP ≤ 95th percentile for Activity Rx
2. Chronic inflammatory age, sex, and height Weight loss as
disease percentile needed
3. HIV 3. LDL-C < 130, TG < 130
4. Nephrotic syndrome Non-HDL-C < 140
4. FG < 100, HbA1c < 7%
ATP Adenosine triphosphate, BMI Body mass index, BP Blood pressure, CHILD 1 Cardiovascular Health Integrated Lifestyle
Diet from the Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and
Adolescents, CKD Chronic kidney disease, CVD Cardiovascular disorder, DM Diabetes mellitus, FG Fibrinogen, HbA
Glycated hemoglobin, HDL-C High-density lipoprotein cholesterol, LDL-C Low-density lipoprotein cholesterol, Rx pre-
scription, TG Triglyceride
–– Step 2: Access CVD risk factors (≥ 2 risk –– LDL > 160 mg/dL with positive family
factors move to high risk) history or one high-risk factor or two mod-
–– Step 3: Risk-specific cutoff points and erate-risk factors
treatment goals –– LDL > 130 mg/dL with two high-risk fac-
–– Step 4: Lifestyle change tors, one high- and two moderate-risk fac-
–– Step 5: Drug therapy tors, or clinical CVD
• Statins:
–– Are the recommended initial medication
Management therapy for dyslipidemia in children and
• Drug treatment: adolescents
–– LDL > 190 mg/dL if there’s no risk factor –– Adverse effects of statins
despite the diet therapy
688 G. Kung et al.
–– Hepatic transaminase level elevation ents with exercise intolerance, gastrointesti-

–– Creatine kinase elevation and rarely epi- nal complaints, and respiratory symptoms.
sodes of rhabdomyolysis • Hypertrophic cardiomyopathy is the most
common cardiac cause of sudden death in
adolescents and young adults.
PEARLS AND PITFALLS
Acknowledgement The authors gratefully
• Exertional chest pain or chest pain associated acknowledge the contributions of Joseph
with palpitations, syncope, abnormal physi- Mahgerefteh, MD, and Daphne T. Hsu, MD, both
cal exam, or family history of significant car- providers in Pediatric Cardiology, Children’s
diac disease should be further evaluated. Hospital at Montefiore, Albert Einstein College of
• Syncope is usually benign in pediatrics, but Medicine, Bronx, New York, to the first edition of
exertional syncope is unusual and can be a this chapter, many of which have been incorpo-
sign of a life-threatening condition. rated into this edition as well.
• Ductal-dependent lesions may not present
until the PDA begins to close.
• Left-to-right shunt lesions may not present References
until the PVR drops and there is increased
shunting. 1. Artman M, Mahony L, Teitel DF, editors.
• Timing of presentation of left-to-right shunt Neonatal cardiology. 3rd ed. New York:
lesions depends on the rapidity of the drop in McGraw Hill Education/Medical; 2017.
PVR as well as the size of the defect. 2. Gewitz MH, Baltimore RS, Tani LY, Sable
• Clinical cyanosis and oxygen saturation are CA, Shulman ST, Carapetis J, American Heart
dependent on hemoglobin, as it takes 5–10 g Association Committee on Rheumatic Fever,
of desaturated hemoglobin to clinically Endocarditis, and Kawasaki Disease of the
appear cyanotic. Council on Cardiovascular Disease in the
• If the patient with a complete AV canal defect Young, et al. Revision of the Jones criteria for
does not develop pulmonary overcirculation, the diagnosis of acute rheumatic fever in the era
it is concerning for elevated PVR. of Doppler echocardiography: a scientific state-
• Kawasaki disease is the most common cause ment from the American Heart Association.
of acquired heart disease in children of devel- Circulation. 2015;131(20):1806–18.
oped countries and usually occurs in children 3. McCrindle BW, Rowley AH, Newburger JW,
under 5 years of age. KD should be treated Burns JC, Bolger AF, Gewitz M, American Heart
with high-dose IVIG as soon as the diagnosis Association Rheumatic Fever, Endocarditis, and
is made. If left untreated, KD leads to coro- Kawasaki Disease Committee of the Council on
nary artery aneurysms in 25% of cases. Cardiovascular Disease in the Young, Council
• Myocarditis is most often due to a viral infec- on Cardiovascular and Stroke Nursing, Council
tion, with enteroviruses (such as coxsackie B on Cardiovascular Surgery and Anesthesia,
virus) commonly associated with viral Council on Epidemiology and Prevention,
myocarditis. et al. Diagnosis, treatment, and long-term
• In neonates and infants, heart failure com- management of Kawasaki disease: a scien-
monly presents as failure to thrive, poor feed- tific statement for health professionals from
ing, respiratory distress, and irritability. In the American Heart Association. Circulation.
older children, heart failure commonly pres- 2017;135(17):e927–99.
19 Cardiology 689
Suggested Reading Liberthson RR. Sudden death from cardiac causes

in children and young adults. N Engl J Med.
Abdurrahman L, Bockoven JR, Pickoff AS, Ralston 1996;334(16):1039–44.
MA, Ross JE. Pediatric cardiology update: Maron BJ, Shirani J, Poliac LC, Mathenge R,
office-based practice of pediatric cardiology for Roberts WC, Mueller FO. Sudden death in
the primary care provider. Curr Probl Pediatr young competitive athletes. Clinical, demo-
Adolesc Health Care. 2003;33(10):318–47. graphic, and pathological profiles. JAMA.
Blake JM. A teen with chest pain. Pediatr Clin N 1996;276(3):199–204.
Am. 2014;61(1):17–28. Menashe V. Heart murmurs. Pediatr Rev.
Burke RJ, Chang C. Diagnostic criteria of 2007;28(4):e19–22.
acute rheumatic fever. Autoimmun Rev. Newburger JW, Takahashi M, Gerber MA,
2014;13(4/5):503–7. Newburger JW, Takahashi M, Gerber MA,
Durani Y, Giordano K, Goudie BW. Myocarditis Gewitz MH, Tani LY, Burns JC, et al. Diagnosis,
and pericarditis in children. Pediatr Clin N Am. treatment, and long-term management of
2010;57(6):1281–303. Kawasaki disease: a statement for health profes-
Expert Panel on Integrated Guidelines for sionals from the committee on rheumatic fever,
Cardiovascular Health and Risk Reduction in endocarditis and Kawasaki disease, council on
Children and Adolescents. Expert panel on cardiovascular disease in the young, American
integrated guidelines for cardiovascular health Heart Association. Circulation. 2004;110:2747.
and risk reduction in children and adolescents: Pilcher TA, Saarel EV. Teenage fainter (dizziness,
summary report. Pediatrics. 2011;128(Suppl syncope, postural orthostatic tachycardia syn-
5):S213–56. drome). Pediatr Clin N Am. 2014;61(1):29–43.
Frank JE, Jacobe KM. Evaluation and manage- Section on Cardiology and Cardiac Surgery.
ment of heart murmurs in children. Am Fam Pediatric sudden cardiac arrest. Pediatrics.
Physician. 2011;84(7):793–800. 2012;129(4):e1094–102.
Hsu DT, Pearson GD. Heart failure in children: Silka MJ. Sudden death due to cardiovascu-
Part I: history, etiology, and pathophysiology. lar disease during childhood. Pediatr Ann.
Circ Heart Fail. 2009;2(1):63–70. 1991;20(7):360–7.
Hsu DT, Pearson GD. Heart failure in children:
Part II: diagnosis, treatment, and future direc-
tions. Circ Heart Fail. 2009;2(5):490–8.
Pulmonology
20
Tanya Martínez-Fernández, Yadira Rivera-Sánchez,
and Preeti Sharma
DIAGNOSTIC TESTING • Forced maneuver breathing from full inspira-

tion (TLC) to RV capturing VC
FOR RESPIRATORY • Displays volume exhaled and flow rates
CONDITIONS –– FVC—volume after full-forced exhalation
–– FEV1—volume exhaled during first sec
Pulmonary Function Testing (PFT) –– FEV1/FVC ratio—low with obstruction
–– FEF 25–75—average flows between 25%
Definition of lung volumes and capacities: and 75% of the maneuver
• Interpreted to show obstruction (low flow),
• 4 volumes:
restriction (low volume), or mixed process
–– IRV inspiratory reserve volume
(Fig. 20.1)
–– TV tidal volume
–– Obstruction: N ↓ FVC, ↓ FEV1, ↓ FEV1/
–– ERV expiratory reserve volume
FVC, ↓ FEF 25–75
–– RV residual volume: Volume at maximal
–– Restriction: ↓ FVC, ↓ FEV1, N FEV1/
expiration
FVC, ↓ FEF 25–75
• Capacities are sums of volumes
• Consider further testing if spirometry is nor-
–– TLC total lung capacity (all four vol-
mal, but positive for asthma-type symptoms:
umes) – volume at maximal inspiration
–– Measurement of spirometry pre and post
–– IC inspiratory capacity: (TV + IRV)
bronchodilator can be used to evaluate for
–– FRC functional residual capacity
airway reactivity
(RV + ERV) – resting volume at the end of
◦◦ Increase in FEV1 after bronchodilator
normal expiration
(significant if > 12% change)
–– VC vital capacity: (RV + ERV +
–– Bronchial challenge testing to measure
TV = TLC – RV)
bronchoconstriction
–– Inhalation challenge or exercise challenge
Spirometry (e.g., methacholine, histamine, cold air,
exercise)
• Provides objective measurements that can be
tracked over time
Lung Volumes
T. Martínez-Fernández (*) · Y. Rivera-Sánchez · P. Sharma

• Useful in evaluation of restrictive lung dis-
Division Respiratory Medicine, Department of Pediatrics, ease (low TLC)
University of Texas Southwestern Medical Center/Children’s
Medical Center Dallas, Dallas, TX, USA
e-mail: tanya.martinez@utsouthwestern.edu

692 T. Martínez-Fernández et al.
Fig. 20.1 Flow volume

loop configurations in
normal and different
pulmonary disorders.
Loop above line is
expiratory loop; loop
below line is inspiratory.
(a) Normal; (b) early
small airway obstruction;
(c) chronic obstructive
disease; (d) variable
extrathoracic large
airway obstruction, e.g.,
vocal cord pathologies;
(e) restrictive diseases
• Measurement of RV impossible with

spirometry
–– Evaluated by
◦◦ Plethysmography (body box)—most
accurate
Hemoglobin Saturation (%)
◦◦ Nitrogen washout, underestimates vol-

ume, if obstructive process present
Diffusion capacity measured with use of carbon

monoxide gas
• Measure of gas transfer across alveolar-capil-

lary barrier
–– May be decreased in interstitial lung dis-
ease, after lung resection
Partial pressure oxygen (pO2)
Pulse Oximetry Fig. 20.2 Oxyhemoglobin saturation curve
• Noninvasive, continuous, and rapid measure

• Limitations of pulse oximetry
of peripheral oxygen saturation (SpO2)
–– Inaccurate readings with poor perfusion,
• SpO2 estimates percentage of hemoglobin
severe anemia, motion artifact, shifts in
bound by oxygen
oxyhemoglobin dissociation curve (e.g.,
• Oxyhemoglobin curve dissociation curve =
acidosis), deep pigmentation of the skin,
relation between partial pressure oxygen
dark nail polish
(pO2) and hemoglobin saturation (Fig. 20.2 )
–– Presence of methemoglobinemia and car-
–– In hypoxia, pO2 is on steep part of curve =
boxyhemoglobin not recognized by most
small pO2 changes, but large SpO2 changes
oximeters and may overestimate SpO2
–– Acidosis, hyperthermia, increase in CO2
–– Co-oximeter used to measure effect of
shifts curve to the right (lower SpO2 for
dyshemoglobinemias
same pO2)
20 Pulmonology 693
Blood Gas Analysis –– Testing with 100% oxygen helps to define:

Response to supplemental oxygen is fair to
• Gold standard for blood gas analysis is an poor, depending on degree of shunt
arterial blood gas (ABG) sample.
• ABG interpretation (see Table 20.1 for ABG Limitations of capillary blood gases (CBG)
values associated with various conditions) • Arterialized CBG obtained by warming of a
• Upper airway obstruction well-perfused heel or earlobe
–– Early increase in pCO2 and proportionate • CBG is more easily attainable than arterial
decrease in pO2. Initially responds well to sample
supplemental oxygen • Values are comparable to arterial pH and
• Intrapulmonary airway obstruction pCO2, but pO2 measurement in CBG is less
–– Mild: Decrease in pCO2, normal to reliable
decreased pO2 • Inaccuracy of blood gas measurements
–– Moderate: Normal pCO2, decrease pO2 increased if sample processing is delayed,
moving toward failure white blood cell (WBC) metabolism contin-
–– Severe: Increase pCO2 and decrease pO2 ues to consume oxygen and results in
–– Supplemental oxygen will support patient, acidosis
but imperative to monitor carbon dioxide
as well
• R-L shunt Chest Imaging
–– Early decrease in pO2
–– Normal or low pCO2, high pCO2 with Suggested modalities for various issues
development of fatigue
Table 20.1 Arterial blood gases: values associated with various conditions
Acid-base abnormality pH pCO2 HCO3 Possible causes
Normal range 7.35–7.45 35–45 21–27
Respiratory acidosis Hypoventilation, neuromuscular
disorders, severe asthma exacerbation,
airway obstruction, intrinsic lung disease,
pneumonia
Acute ↓ ↑ N
Compensated N↓ ↑ ↑
Respiratory alkalosis Pain, hyperventilation, pulmonary
embolism, high altitude
Acute ↑ ↓ N
Compensated N↑ ↓ ↓
Metabolic acidosis Methanol, diabetic ketoacidosis, inborn
error of metabolism, lactic acidosis,
salicylates, diarrhea, shock
Acute ↓ N ↓
Compensated N↓ ↓ ↓
Metabolic alkalosis Vomiting, diuretics, primary
aldosteronism
Acute ↑ N ↑
Compensated N↑ ↑ ↑
N Normal
• Plain chest radiograph (CXR) GENERAL SIGNS

–– Upright views: Atelectasis, pneumonia,
pneumothorax
AND SYMPTOMS
–– Inspiratory and expiratory or bilateral decubi-
Stridor/Wheezing
tus views for suspected foreign body may be
able to see asymmetric hyperinflation inside Background
with foreign body due to check valve effect • Wheezing
◦◦ Most foreign bodies not seen, as they are –– A musical, high-pitched whistling sound
radiolucent produced by airflow turbulence
◦◦ In bilateral decubitus views, dependent –– One of the most common symptoms in
side should have lower volume (like asthma (see amplified discussion)
expiratory view) than upright side • Stridor
–– Decubitus views: Pleural fluid, –– High-pitched, harsh sound often audible
pneumothorax without the stethoscope
• Fluoroscopy: Tracheomalacia, diaphrag- –– Results from rapid, turbulent airflow
matic movement through a partially obstructed airway
• Upper gastrointestinal (UGI) series: • Inspiratory versus expiratory
Vascular ring, tracheoesophageal fistula –– Inspiratory—Extrathoracic swelling or
• Video swallow study: Aspiration obstruction will lead to airway collapse on
• Ultrasound: Pleural effusion, complicated inspiration. Example: Laryngomalacia
pneumonia, diaphragm –– Expiratory—Intrathoracic swelling or
• Computed tomography (CT) scan: obstruction will lead to airway collapse on
–– Best at providing images of lung anatomy, expiration. Example: Tracheomalacia
airway tree, parenchyma, and vascular –– Biphasic stridor—Indicates fixed airflow
structures obstruction, subglottic space obstruction
–– High resolution: Better to evaluate paren-
chyma like in bronchiectasis or interstitial
lung disease ifferential Diagnosis of Acute
D
–– Contrast: Used to evaluate for lymphade- Stridor
nopathy, masses, vascular abnormalities,
arteriovenous malformations, pulmonary • Croup or laryngotracheobronchitis (see
embolism amplified discussion)
• Positron emission tomography (PET) scan: • Foreign body aspiration (see amplified
Anterior, middle mediastinal masses, discussion)
lymphoma –– Most common between 1 and 3 years of
• Ventilation-perfusion scan: Pulmonary age
embolism –– Sudden onset with cough, stridor, or
• Magnetic resonance imaging (MRI): wheezing
Vascular lesions, mediastinal and chest wall • Bacterial tracheitis (see amplified
masses discussion)
20 Pulmonology 695
• Spasmodic croup or acute spasmodic • Flexible laryngoscopy can confirm the diag-
laryngitis nosis but may miss tracheal abnormalities
–– Children 6 months to 5 years that can be identified with bronchoscopy
–– No viral etiology but symptoms similar to • If moderate to severe obstruction, difficulty
viral croup with feeding and breathing, or unable to gain
–– May be triggered by gastrointestinal (GI) weight, flexible or rigid bronchoscopy to rule
reflux out other associated airway anomalies
• Retropharyngeal abscess
–– Preschool age group Management
–– Abrupt onset of high fevers, difficulty • Usually benign and self-limiting and improves
swallowing, refusal to feed, sore throat, as the child reaches 1–2 years of age
hyperextension of the neck or torticollis, • Careful observation and growth monitoring
and respiratory distress for most patients
• Peritonsillar abscess • Surgical correction may be considered in
–– Preadolescents and adolescents severe cases
–– Severe throat pain, trismus, muffled voice, • Resolution of symptoms for most patients
trouble swallowing or speaking without therapy in early childhood
• Allergic reaction or anaphylaxis
–– Associated with itchiness or hives Choanal Atresia
–– History of allergy • 50% associated with congenital anomalies
(i.e., CHARGE association, mnemonic for
Coloboma, Heart defects, Choanal atresia,
Differential Diagnosis of Chronic Retarded growth and development, Genital
Stridor abnormalities, and Ear anomalies)
• Bilateral—medical emergency during neona-
Laryngomalacia tal period, intermittent respiratory distress
• Most common cause of stridor in infants relieved by crying
• Accounts for up to 75% of all causes of • Unilateral—chronic mucoid nasal discharge
stridor on affected side in older infants/young
children
Clinical presentation • Diagnosis: Inability to pass a 6F catheter into
• Onset shortly after birth, minimal respiratory oropharynx through nose
distress, positional effects, and marked reduc- • Management: Surgical
tion of noise when infant is at rest
• May present with apnea and feeding Vocal Cord Paralysis (VCP)
difficulties • Second most common cause of stridor in
• Stridor improves in prone position with head infants
elevated and worsens in supine position • May result from local trauma
• Associated with normal voice quality and • Left side VCP may result from trauma to the
pitch recurrent laryngeal nerve at birth or surgical
trauma
Diagnosis • Unilateral—congenital or secondary to birth
• Diagnosis cannot be established on the basis or surgical trauma such as cardiothoracic
of standard radiograph of the neck surgery
• Bilateral—associated with central nervous • Emergency tracheostomy is required to

system abnormalities such as Arnold-Chiari relieve obstruction caused by a complete
malformation, tumors, or increased intracra- laryngeal web
nial pressure
Subglottic Stenosis (SGS)
Clinical presentation • SGS may be congenital (rare and usually
• Unilateral VCP—hoarse voice, weak cry, and associated with other genetic syndromes or
biphasic stridor that is louder when awake. conditions) or post-traumatic (due to airway
Improves when lying with the affected side instrumentation or more commonly,
down intubation)
• Bilateral VCP—high-pitched biphasic stridor –– Even brief periods of intubation may result
that may progress to severe respiratory distress. in chronic SGS
Rarely associated with abnormal vocalization • Airway inflammation secondary to trauma
• Bilateral VCP is associated with increased may lead to acquired SGS
risk of recurrent aspiration • The cricoid cartilage, being a complete ring,
• VCP may be an early sign of brain stem or is predisposed to traumatic injury and
spinal cord compression stenosis
Imaging Clinical presentation
• MRI of the upper spinal cord and brain stem • History of recurrent croup, a protracted croup
may be required in evaluating patients with illness, previous intubation or airway
unexplained bilateral VCP instrumentation
• Biphasic stridor
Management • Retractions, flaring, high-pitched stridor, and
• Presence of aspiration and the degree of air- diminished air entry are associated with sig-
way obstruction—primary indicators of need nificant SGS
for therapy in patients with VCP • Hypoxemia or carbon dioxide retention in a
• Continuous positive pressure may provide child with SGS indicates a severe obstruction
temporary relief of symptoms of VCP leading to marked hypoventilation
• Decompression surgery is required to relieve
VCP secondary to Arnold-Chiari malformation Diagnosis
• Traumatic VCP should improve in 6 months • Spirometry will demonstrate flattened inspi-
and, if not, unlikely to improve thereafter ratory loops
• Endoscopy will demonstrate narrowing of the
Laryngeal Web subglottic space
• Strong association with velocardiofacial syn- • No correlation between the radiographic
drome (chromosome 22q11.2 deletion) appearance of SGS and actual degree of nar-
• Posterior glottic webs are acquired from pro- rowing on direct visualization
longed intubation
• Laryngeal webs may be associated with ante- Management
rior subglottic stenosis • If subglottic space only allows an endotra-
• Weak cry and biphasic stridor cheal tube (ETT) two sizes smaller than
expected, consider surgical intervention
Management • A cricoid split procedure may provide an
• Surgery can be curative if significant obstruc- alternative to tracheostomy in infants with
tion occurs SGS
20 Pulmonology 697
Subglottic Hemangioma Management

• Rare cause of upper airway obstruction in • Type 1—Conservative management with
children swallow therapy and thickening of feedings
• Types 2–4—Surgical intervention and swal-
Clinical presentation low therapy
• Considered in the differential diagnosis of
chronic upper airway obstruction Macroglossia
• 50% accompanied by cutaneous hemangio- • Macroglossia predisposes patients to obstruc-
mas of head and neck tive sleep apnea (OSA)
• Inspiratory or biphasic stridor that worsens as • Lateral-view radiograph to evaluate anatomic
hemangiomas enlarge relationship between tongue and airway
• Likely to shrink with age and usually do not • Prone positioning may help in the acute man-
require therapy agement of airway obstruction due to
macroglossia
Diagnosis • Airway obstruction may improve with age
• Upper airway endoscopy—asymmetric com-
pressible bluish mass in the subglottic space
Cough
Management
• Treatment options include steroids, laser, Background
intralesional steroid injections, and open sur- • Cough sensors present in upper and lower air-
gical excision way mucosa, paranasal sinuses, upper GI
• Propranolol from months to years by center tract, external auditory canal
with expertise • Nocturnal cough is rare in normal children
• Tracheostomy in severe obstruction
• Differential is wide, so narrow possible diag-
Laryngotracheoesophageal Cleft
noses with history and physical:
• Associated with tracheoesophageal fistulas
–– Age, exposures, family history of asthma,
• Rare cause of recurrent aspiration
allergies, or lung disease
• Neonates with severe clefts may present with
–– Type of cough
respiratory distress
◦◦ Wet, dry, frequency, diurnal, nocturnal,
• Defect involves the anterior wall of the upper
length of cough, seasonality, quality,
esophagus and the posterior aspect of the lar-
presence of hemoptysis
ynx, with the defect lying in the interaryte-
◦◦ Sputum production (bronchitis, cystic
noid space
fibrosis [CF], primary ciliary dyskinesia
Clinical presentation [PCD], bronchiectasis)
• Recurrent aspiration and cyanosis with ◦◦ Quality
feeding are the most common clinical ▪▪ Brassy (tracheal irritation,
presentation tracheomalacia)
▪▪ Barky (croup)
Diagnosis ▪▪ Honking (habit cough)
• Direct laryngoscopy rather than transnasal ▪▪ Staccato (chlamydia, mycoplasma)
fiber-optic endoscopy is the diagnostic ▪▪ Paroxysmal/whoop (pertussis, CF,
method of choice foreign body)
–– Association to feedings and exercise (aspi- Evaluation of chronic cough

ration, exercise-induced asthma)
–– Associated with persistent rhinitis: aller- Look for clues and pointers and tailor evalua-
gies, PCD tion according to most likely diagnoses:
–– Recurrent pneumonia—immunodeficiency • CXR
–– If not present during sleep in school age/ • Pulmonary function (spirometry)
adolescent, consider habit cough • Sputum culture
–– Nighttime cough: asthma, sinusitis • Allergy testing
–– Response to medications • Swallow study
–– Useful physical findings: stridor, wheez- • Sweat test
ing, clubbing, poor growth, eczema, tachy- • Immune function testing, including complete
pnea, focal auscultatory findings, chest blood count (CBC) with differential,
wall abnormalities immunoglobulins
• Acute cough usually resolves in 1–3 weeks in • Purified protein derivative (PPD) test
90% of children • Consider chest CT if cough is productive
• Subacute cough lasts 3–8 weeks and chronic • Echocardiogram
cough > 8 weeks • Refer to specialists for further evaluations,
e.g., laryngoscopy, bronchoscopy,
Differential diagnosis echocardiogram
Considerations by length of cough: Management

• Acute: Allergies, foreign body, upper respira- • Recurrent respiratory tract infections/postin-
tory tract infections fectious cough: Symptomatic therapy
• Subacute: Postinfectious cough, viral, • Upper airway cough syndrome:
pertussis Antihistamines, nasal steroids
• Chronic cough: • Dry cough/wheezing: Trial bronchodilators
–– All age groups: Gastroesophageal reflux with environmental modifications. If positive
(GER), exposures (tobacco smoke, response, consider trial with inhaled cortico-
pollution) steroids (ICS)
–– Other considerations by age: • GER: Antacids
◦◦ Infants: Aspiration, congenital airway • Psychogenic cough: Behavioral modifications
abnormalities, CF (even if neonatal • Further management based on diagnostic
screen is normal), neonatal infection, findings: Refer to specialists for complicated
chlamydia, congenital heart disease diagnoses
(CHD)
◦◦ Toddlers/preschoolers: Upper respira-
tory infection (URI), asthma, foreign Tachypnea
body, postinfectious cough, pertussis,
mycoplasma, immunodeficiencies, • Definition by age (breaths/min):
bronchiectasis, CF –– Birth to 30 days > 60
◦◦ School age/adolescents: Asthma, upper –– 2 to 12 months > 50
airway cough syndrome, smoking, –– 1 to 5 years old > 40
tuberculosis (TB), bronchiectasis, habit –– Older than 5 > 20
cough –– Subtract 10 if the child is febrile
20 Pulmonology 699
Exercise Intolerance Apnea

• The reference standard is the maximal oxy- • Defined by reduced or cessation in respira-
gen consumption (VO2 max) tory airflow
• Pulmonary conditions
–– Most common: Exercise-induced asthma Three main types
(EIA) and CF • Central
• Less common: Interstitial lung diseases –– Cessation of airflow secondary to reduc-
• Cardiovascular conditions tion or lack of excitatory signals from cen-
–– Congestive heart failure and CHD (most tral nervous system (brain stem) to
common CHD = tetralogy of Fallot) respiratory muscles
• Muscular conditions, especially those associ- –– No chest wall effort
ated with neuromuscular weakness –– Prolonged episodes (> 20 s) are more clini-
–– Duchenne muscular dystrophy cally significant and usually associated
• Hematologic disorders with cyanosis and/or bradycardia
–– Iron deficiency anemia –– Shorter episodes can be seen in periodic
–– Sickle cell disease breathing, which is common in premature
• Vocal cord dysfunction infants and decreases with age/maturation
–– Paradoxical motion of vocal cords • Obstructive
◦◦ More common in adolescent females –– Airway (usually upper airway) obstruc-
◦◦ May mimic EIA—Need to consider if tion/collapse leading to partial or complete
not responding to EIA treatment obstruction of airflow in spite of chest wall
• Sedentariness—Leads to deconditioning, effort
muscle weakness, and obesity • Mixed
–– Combination of both central and obstruc-
tive components
Respiratory Failure –– Usually central component followed by
obstructive
• Type 1 respiratory failure characterized by
low blood oxygen levels (hypoxemia, low Differential diagnosis of central apnea
pO2, normal or decreased pCO2, and alveo- • Neonates/infants:
lar-arterial oxygen gradient (pA-aO2) is –– Can present with central or mixed apnea
increased) –– Most common cause: Apnea of prematu-
–– Causes: V/Q mismatch, decreased minute rity or apnea of infancy
volume, diffusion impairment or shunt ◦◦ Associated with immature respiratory
• Type 2 respiratory failure affects both oxygen centers, laryngeal reflex, and, when
and carbon dioxide levels mixed, underdeveloped upper airway
–– Low pO2, high pCO2, normal pA-aO2 musculature
–– Causes: Reduced breathing effort, ◦◦ Usually resolves by 48–53 weeks post-
increased airways resistance, neuromuscu- conceptional age
lar disease ◦◦ Can be treated with respiratory stimu-
• Treating the underlying cause is paramount. lants (e.g., caffeine) or continuous posi-
In severe cases, intubation and mechanical tive airway pressure (CPAP)
ventilation are required ◦◦ Further evaluation warranted in younger
• If related to respiratory depression is related infants (< 2 months) and severe presen-
to narcotics, reversal can be of benefit tations requiring resuscitation
–– Other causes of apnea during infancy usu- • Hematologic causes include methemoglobin-
ally more severe and include: emia and polycythemia
◦◦ Infection (e.g., sepsis, pneumonia, men- • Can be caused by high altitude and
ingitis, pertussis, bronchiolitis, botulism) hypothermia
◦◦ Head trauma, intraventricular hemor-
rhage, seizure, medications Evaluation
◦◦ GER, necrotizing enterocolitis • Assessment of respiratory status—wheezing,
◦◦ Metabolic derangements such as hypo- distress
glycemia and acidosis, inborn errors of • Cardiac assessment to include echo, and if
metabolism concern for intrapulmonary shunt, consider
◦◦ Hyper- or hypothermia contrast (bubble) echo
◦◦ Heart failure • ABG
◦◦ Anemia • Methemoglobin assessment
◦◦ Congenital central hypoventilation
syndrome
• Older children Chronic Hypoxia
–– Causes: Cerebral hemorrhage or infarc-
Causes
tion, brain tumor, seizures, hypoxic injury,
• Pulmonary venous desaturation
spinal cord injury, drugs, medications
–– Lung disease with diffusion impairment
Evaluation
(interstitial lung disease)
• Guided by history (see amplified discussion
–– Intrapulmonary right-to-left shunting (pul-
for ALTE/BRUE)
monary arteriovenous malformations)
• If severe presentation, young infant or older
• Extrapulmonary/intracardiac right-to-left
child, consider:
shunting
–– CBC, serum glucose, electrolytes
–– Cyanotic CHD (tetralogy of Fallot, pulmo-
–– Sepsis workup
nary atresia)
–– Electrocardiogram (ECG)
–– Pulmonary hypertension can present with
–– Neuroimaging, electroencephalogram if
intracardiac right-to-left shunting
clinically indicated
• Hemoglobin disorders with decreased oxy-
–– Consult pertinent specialists
gen affinity
–– OSA (see amplified discussion for OSA)
–– Methemoglobinemia (see expanded
discussion)
Cyanosis
Diagnosis
Background • Hyperoxia test
• Bluish tint of the skin, either centrally or –– Give 100% oxygen and obtain a preductal
peripherally, related to respiratory causes, blood gas (i.e., right upper extremity)
central nervous system causes, or hemato- –– Normal PaO2 > 500 mmHg
logic causes –– Pulmonary disease PaO2 > 150 mmHg, but
• Pulmonary causes are a result of poor oxygen < 500 mmHg
delivery –– Right-to-left shunting PaO2 < 150 mm Hg
• Cardiac causes include CHD and heart • CXR to evaluate for pulmonary pathology
failure • CBC—If chronic, will show polycythemia
20 Pulmonology 701
Methemoglobinemia • Biliary cirrhosis

• Infective endocarditis
Background • Normal variant as a familial trait
• Methemoglobin (MetHb) cannot carry oxy-
gen to tissues Diagnosis
• Methemoglobin occurs with oxidation of fer- • Obliteration of the angle between the proxi-
rous (Fe2+) to ferric (Fe3+) hemoglobin mal nail and soft tissue of the digit (Schamroth
• Methemoglobinemia can be acquired or sign)
inherited • Normal anatomy shows a diamond-shaped
–– Acquired space when placing the distal phalangeal
◦◦ Most common after exposure to exoge- joints in mirrorlike fashion
nous oxidizing agent like nitrites
▪▪ Intestinal bacteria can convert nitrates
in well water and pureed leafy vegeta- Hemoptysis
bles to nitrites
Background
◦◦ Dehydration
• Hemoptysis (coughing blood) is uncommon
–– Inherited
but can be a serious manifestation of pulmo-
◦◦ Deficiency cytochrome-b5 reductase
nary disease in children
◦◦ Hemoglobin M disease
• Pulmonary vasculature composed of two-
Clinical Presentation pressure system:
• Presents as cyanosis with MetHb levels > 15% –– Bleeding from low-pressure pulmonary
• Cyanosis with normal pulse oximetry, no vessels (e.g., diffuse hemorrhage) leads
respiratory or cardiac findings on physical to small-volume hemoptysis, while bleed-
exam ing from systemic pressure bronchial
vessels (e.g., bronchiectasis) tends to be
Evaluation profuse
• Pulse oximetry—May be normal, but does
not increase with use of oxygen Clinical presentation
• Blood gas—Chocolate-colored blood • Differentiating from hematemesis (vomiting
• Co-oximetry blood) and epistaxis (nasal bleeding) can be
tricky
Management • Most common reason for symptom usually
• Oxygen not true hemoptysis but bleeding from upper
• Severe cases: Methylene blue, N-acetylcysteine, airway (e.g., nasal bleeding)
exchange transfusion • Diffuse hemorrhage is frequently slow and
may present only with anemia and fatigue
lubbing of Digits or Hypertrophic

C Differential Diagnosis
Pulmonary Osteodystrophy • Most common etiology of true hemoptysis is
inflammation or infection
Causes • More common
• The most common cause is cyanotic heart –– Upper airway and GI bleeding
disease –– Infection such as bronchitis, pneumonia,
• The most common pulmonary causes are CF lung abscess, TB, fungal infections
and bronchiectasis (usually more advanced – – Foreign body
disease) –– Cystic fibrosis, bronchiectasis
• Less common RESPIRATORY CONDITIONS

–– Airway trauma
–– Tracheostomy
OF THE UPPER AIRWAY
–– Cardiac (CHD, pulmonary hypertension, See discussion on stridor for general
pulmonary embolism) considerations
• Rare
–– Airway tumor (e.g., carcinoid)
–– Arteriovenous fistula Viral Croup
–– Bleeding disorder (Laryngotracheobronchitis)
–– Idiopathic pulmonary hemosiderosis
–– Pulmonary renal syndromes (usually in Background
older children) • Most common cause is parainfluenza
◦◦ Granulomatosis with polyangiitis, • Causes subglottic narrowing
Goodpasture syndrome, systemic lupus • Common between 3 months and 3 years
erythematosus, microscopic polyangi- • Spasmodic croup similar without viral pro-
itis, Henoch-Schönlein purpura drome or other identifiable cause
–– Factitious hemoptysis • Cricoid cartilage has a complete ring and is
the narrowest part of the airway in infants
Evaluation –– Edema at this level will lead to further nar-
• History and physical exam not usually help- rowing, increased airway resistance, and
ful; other guided studies frequently useful in possible airway compromise
the investigation
–– Imaging including CXR or chest CT with Clinical presentation
contrast to localize lesion or find evidence • Barking or brassy cough
of pulmonary hemorrhage • URI with or without fever, which may be high
–– Helpful labs: CBC for anemia; erythrocyte (39–40 °C)
sedimentation rate (ERS), kidney function, • Respiratory distress with retractions with
urinalysis for renal involvement or inflam- hypoxia and hypercapnia in severe upper air-
matory disease way obstruction
–– Bronchoscopy can identify area of active • Child may prefer to sit or be held upright
bleeding and should include upper airway • Mild—no stridor at rest
evaluation. Bronchoalveolar lavage for evi- • Moderate—stridor at rest but no agitation
dence of infection or hemosiderin-laden • Severe—stridor and agitation
macrophages (presence indicates previous • Recurrent croup: Consider underlying ana-
bleeding) tomic airway abnormality, GER, or atopy
–– Echocardiogram for cardiac disease
Diagnosis
Management • Clinical diagnosis
• Massive blood loss requires acute resuscita- • In typical cases, CXR is not required
tion with volume, blood products, and sup- –– CXR findings—steeple sign on frontal
portive care with oxygen and mechanical view is a common finding but may be
ventilation absent
• Evaluation by subspecialists (ear/nose/throat
(ENT), pulmonologist, gastroenterology, Management
rheumatology), depending on suspected cause • Reassurance, observation, and hydration
20 Pulmonology 703
• Dexamethasone 0.6 mg/kg beneficial in Epiglottitis

mild croup (may decrease need for
hospitalization) Background
• Oxygen and racemic epinephrine in moderate • Most common pathogen Haemophilus
or severe cases influenzae
• Racemic epinephrine does not lead to rebound • Rare in children due to H. influenzae vaccina-
worsening of obstruction, but patient may tion, which leads to individual and herd
worsen when drug effects subside. A 2-h immunity
observation is important. Worsening of • More common in the elderly and immune-
obstruction is unlikely to occur if patient does compromised children than in the general
well after 4 h. population
• Racemic epinephrine should be used cau- • Uncommon pathogens that can cause epiglot-
tiously in patients with left ventricular outlet titis: Herpes viruses and fungi
obstruction • Pathology involves the epiglotis and other
• Low-density gas such as helium-oxygen supraglottic structures, but the subglottic
(heliox) may be effective in children with space and trachea are usually spared
severe croup
–– Turbulent flow through large airways is Clinical presentation
density-dependent. • Rapid onset of illness (hours) with high fever,
–– By decreasing gas density, airflow resis- sore throat, drooling with difficulty swallow-
tance can be decreased. ing, and difficulty breathing
• Admit for severe distress, hypoxia, and inabil- • Patient sitting up and leaning forward posi-
ity to feed/drink or if requiring 2 or more tion to enhance airflow
racemic epinephrine treatments • Stridor is not a prominent feature
• Endotracheal intubation recommended before • Radiograph lateral neck view: Thumb sign
patient is restless and cyanotic
• Endotracheal intubation using an ETT one Management
size smaller than predicted tube size (based • Patients with acute epiglottitis should undergo
on age and weight) is the preferred method of endotracheal intubation to ensure an adequate
establishing an artificial airway in patients airway until inflammation subsides
with viral croup • In severe cases, avoid unnecessary studies
• Intubation more likely for bacterial tracheitis until airway is secured
and epiglottitis and rare in croup • A skilled provider needs to remain with a
• If intubation needed, consider measles or patient with epiglottitis until the airway is
influenza A visualized and secured
Prognosis
• Course of viral croup in infants younger than B
acterial Tracheitis
1 year of age is prolonged
Background
• Symptoms often improve during the day with
• Most common organisms are Staphylococcus
recurrence of symptoms in the early hours of
aureus, Moraxella catarrhalis, and
the morning
Streptococcus
• Mean age is 4 years (range 4 weeks to May be associated with diaphragmatic hernia
13 years, typically about 2 years) and colonic duplication
• Intralobar: Typical in the lower lobe, sys-
Clinical presentation temic arterial supply, variable venous drain-
• Brassy and barky cough, but the patient has age, and airway connections
high fever and appears very toxic with respi-
ratory distress and stridor Clinical presentation
• Patient may lay flat and does not have drool- • Dullness on percussion, decreased breath
ing or dysphagia associated with epiglottitis sounds over the lesion, continuous murmur
• Rapid progression and purulent secretions may be heard on the back, and crackles if
may mandate early endotracheal intubation infected
• Does not respond to racemic epinephrine or
corticosteroids Evaluation
• Fetal ultrasound or ultrasound following birth
Diagnosis may detect pulmonary mass
• CXR not needed but may show the classic • CT scan with contrast confirms diagnosis
findings of pseudomembrane detachment in
the trachea Management
• High fever, purulent airway secretions, • Surgical removal because retained sequestra-
absence of findings of epiglottitis tions have a small possibility of becoming
malignant
Management • Consultations: Pulmonology and surgery
• Intubation, especially for younger patients;
50–60% do not require intubation Bronchogenic Cyst
• Humidification and careful suctioning of the
ETT are important Background
• Antistaphylococcal treatment (i.e., nafcillin • Arise from abnormal budding of the tracheal
or vancomycin) diverticulum
• Prognosis is good • Patient may become symptomatic if the cyst
• Complications can include ARDS, toxic enlarges or becomes infected
shock, septic shock, pulmonary edema, and • May be asymptomatic and found incidentally
subglottic stenosis
• Fever, chest pain, and productive cough are
RESPIRATORY CONDITIONS the most common presenting symptoms
• Dysphagia, if causing pressure on the sur-
OF THE LOWER AIRWAY rounding structures
AND PARENCHYMA • CXR can show the cyst, but CT or MRI demon-
strates anatomy (usually medial mediastinum)
ongenital Airway and Pulmonary
C
Malformations Management
• Surgical removal
Pulmonary Sequestration
Vascular Ring/Sling
Background
• Extralobar: More common in males; 65% in Background
the left lung, covered by pleura, fed by sys- • Congenital anomalies of the large vessels
temic artery, and drained via systemic vein. (such as aortic arch)
20 Pulmonology 705
• May involve airway and/or esophagus ongenital Pulmonary Adenomatoid

C
• Variable severity and timing of presentation Malformation
but, if significant, usually presents during
infancy Background
• More prevalent in the left lower lobe
Clinical presentation • 5 subtypes
• May cause stridor or wheezing, cough, apnea, –– Most are Type 1 (70%): Large (> 5 mm)
failure to thrive, and/or dysphagia single or multiple cysts
• Imaging: –– Type 3 (10%): Microcystic, solid, and
–– Echocardiogram, CT, and MRI help define associated with other anomalies. Worse
anatomy. Can be associated with tracheo- prognosis
malacia secondary to airway compression
–– Esophagogram may indirectly diagnose by Clinical presentation
demonstrating compression of abnormal • Asymptomatic to respiratory distress depend-
vessel upon esophagus ing on extent
Management Evaluation
• Surgical intervention • Can be identified by prenatal ultrasound
• CT scan is diagnostic
Tracheal Stenosis
Management
Background • Resection if respiratory distress, markedly
• Narrowing of tracheal lumen frequently asso- symptomatic
ciated with complete tracheal rings • If asymptomatic, can observe, but eventually
• Can vary from short- to long-segment most are surgically removed
stenosis –– Even if asymptomatic, there is increased
• Condition is rare future risk for infections and small risk for
malignancy
• Varies depending on degree of obstruction
• If severe, presents during neonatal period or Congenital Lobar Emphysema
infancy with respiratory distress, cyanosis,
stridor, cough, and dysphagia Background
• Congenital bronchial obstruction leads to air
Diagnosis trapping and distention of involved lung
• Direct visualization via rigid bronchoscope • Rare
• CT scan could be used to reconstruct via “vir- • Prevalence: Left upper lobe > right middle
tual bronchoscopy” lobe/right lower lobe
• Echocardiogram to evaluate associated CHD
Management • Usual presentation in infancy with respira-
• Surgical intervention tory distress, tachypnea, hypoxemia
• Refer to pediatric ENT or airway surgical
specialist Diagnosis
• CXR
–– Initially may present in neonate with opaci- • A lack of radiographic findings does not
fication due to fluid exclude an airway FB; many objects are
–– Subsequently, there is hyperinflation with organic and likely to be radiolucent
shift to contralateral side • Positive radiographic findings include hyper-
• Confirmation with CT scan inflation, atelectasis, or infiltrate
• Soft tissue film of the neck can be of benefit
Management to detect objects in the upper airway
• Surgical resection/lobectomy • Patients with tracheostomy are at a higher
risk
OREIGN BODY (FB)

F Management
ASPIRATION • Ideal treatment is prompt removal with rigid
bronchoscopy
Background • Can defer bronchoscopy until proper hydra-
• Nuts, particularly peanuts, make up one-third tion and emptying of the stomach
of cases
• Round, globular FBs (hot dog, grapes, nuts, Complications
hard candies) are the most frequently found, • Retained foreign body can lead to hemopty-
causing a complete airway obstruction sis, lung abscess, and ultimately
• Most common in age < 3 years bronchiectasis
• Initial event: Violent, paroxysmal coughing, PULMONARY HEMOSIDEROSIS
choking, gagging, possible airway obstruc-
tion if the FB is large Background
• Asymptomatic interval: FB becomes lodged, • Repeated episodes of intra-alveolar bleeding
reflexes fatigue, immediate irritation sub- that leads to abnormal accumulation of iron
sides. This stage is most dangerous and (hemosiderin) in the alveolar macrophages
accounts for delayed diagnosis • Subsequent development of pulmonary fibro-
–– In this stage, FB might be missed, as physi- sis and severe anemia
cian is reassured by the absence of
symptoms Causes and associated conditions
• A positive history must never be ignored, and • Idiopathic pulmonary hemosiderosis (IPH)
negative history can be misleading • Secondary pulmonary hemosiderosis
• Coughing or choking episode accompanied –– Cardiovascular:
by wheezing is highly suggestive of FB in the ◦◦ Congestive heart failure
airway. ◦◦ Pulmonary hypertension
• Must question about nuts, small toys, other ◦◦ Mitral valve stenosis
small items – – Inflammatory/autoimmune
• 58% lodge in the right bronchus ◦◦ Goodpasture syndrome
◦◦ Rheumatoid arthritis
Diagnosis ◦◦ Wegener granulomatosis
• CXR is negative in 10–30% of cases ◦◦ Henoch-Schönlein purpura
• If there is suspicion for FB, patient should – – Allergic
undergo inspiratory and expiratory CXRs; in –– Heiner syndrome (cow’s milk
the uncooperative patient, consider doing hypersensitivity)
bilateral decubitus films
20 Pulmonology 707
Clinical presentation • Other common causes are human metapneu-

• Iron deficiency anemia movirus, parainfluenza, adenovirus, influ-
• Hemoptysis (helpful if occurs, but enza, rhinovirus, and mycoplasma
infrequent)
• Alveolar infiltrate Risk Factors
• Presence of hemosiderin; it takes 48–72 h for • Maternal asthma
macrophages to convert erythrocyte to • Maternal smoking
hemosiderin • Persistent rhinitis
• Widely variable from asymptomatic with • Eczema at < 1 year of age
infiltrates and anemia to shock and sudden
death Clinical presentation
• After episode of hemorrhage, the patient will • Nasal congestion, rhinorrhea, and cough
present with wheezing, cough, dyspnea, bron- • Tachypnea or elevated respiratory rate is the
chospasm, and alteration of blood gases earliest and most sensitive vital sign change
• Nasal flaring, grunting (in infants), and supra-
Diagnosis sternal, intercostal, and subcostal retractions
• Best guided by consulting pulmonologist are evidence of increased respiratory effort
• Recurrent “pneumonia”, fever, cough, CXR • Nasal suctioning and repositioning may allow
abnormalities for a more accurate assessment of lower
• Hypochromic microcytic anemia respiratory tract involvement
• Elevation of plasma bilirubin • Common: Crackles, wheezing, and referred
• Infiltrates are typically bilateral and may upper airway sounds upon auscultation
spare the apices, often with hyperaeration • Apnea may be more prominent than wheez-
• IgE, cow’s milk antibody levels, stool speci- ing in infants < 2 months or former preterm
men for heme infants
• Urinalysis for nephritis • Symptoms can range from mild tachypnea to
• Antinuclear antibodies (ANA), antineutro- frank respiratory failure
phil cytoplasmic antibodies (ANCA), and • Clinical course is expected to worsen, with
anti-glomerular basement membrane (GBM) peak symptoms noted around days 3–4 of ill-
• Lung biopsy if diffuse alveolar hemorrhage ness (“day of illness”)
(DAH) • “Day of illness” is an important variable for
providing anticipatory guidance for outpa-
Management tient management and in making decisions
• Corticosteroid is the treatment of choice for regarding admission and discharge of patients
IPH
• Treatment is highly dependent on the under- Diagnosis
lying cause • Clinical symptoms lead to diagnosis; subse-
quent evaluation is important in determining
treatment
ACUTE BRONCHIOLITIS • Initially must assess respiratory rate and oxy-
gen saturation because work of breathing,
Background tachypnea, and hypoxia are most clinically
• Viral bronchiolitis is the most common lower significant in determining severity
respiratory tract infection in those under • CXR warranted for infants in respiratory
2 years of age distress
• Respiratory syncytial virus (RSV) is responsi- • CXR commonly demonstrates hyperinflation,
ble for more than 50% of acute bronchiolitis patchy atelectasis, and infiltrates
• In infants under 30 days old, the risk for seri- BRONCHOPULMONARY

ous bacterial infection (SBI) warrants full
evaluation for SBI and administration of
DYSPLASIA (BPD)
empiric antibiotics Background
• Recognize that infants older than 30 days • Definition has changed since initial descrip-
with bronchiolitis are at a lower risk for SBIs, tion in the 1960s
thus allowing for decreased invasive testing • “Old” BPD in late premature infants treated
and observation without administering antibi- with high peak inspiratory pressures and high
otics to patients who have classic oxygen concentrations leading to necrotizing
presentations bronchiolitis, pulmonary hypertension, alve-
olar overinflation, atelectasis, cystic disease,
Management
and pulmonary fibrosis
• Mainstay of treatment is supportive: Oxygen
• “New” BPD definition revised in 2000 after
for hypoxia, hydration, nasal suctioning, and
use of CPAP, gentler ventilation, antenatal
positioning to elevate chest to 30°
steroids, and surfactant instituted as standard
• When feeding adequately and work of breath-
–– Immature lung resulting in alveolar arrest
ing improves, oxygen can be discontinued if
and dysmorphic pulmonary vasculature;
saturations are 90–92% for most of the time
lung injury from oxygen therapy, positive-
• Infants with respiratory distress and desatura-
pressure ventilation, infection, inflamma-
tion or dehydration should be hospitalized
tion, and fluid overload; and inadequate
• The American Academy of Pediatrics does
lung injury repair with ongoing
NOT recommend the use of bronchodilators
inflammation
or systemic steroids in the routine treatment
–– Other risk factors: lower birthweight, ges-
of bronchiolitis
tational age (< 32 weeks), chorioamnion-
• However, those with recurrent wheezing may
itis, and Ureaplasma colonization
respond to bronchodilator therapy
• Corticosteroid medications, inhaled or admin- Clinical Presentation
istered systemically, should not be routinely • Need for oxygen, which can progress to respi-
used in the treatment of bronchiolitis ratory failure leading to increased or progres-
• If bronchodilator makes the wheezing worse sive need for ventilatory support
or increases work of breathing, consider pul- • Grading of “new” BPD based on ongoing
monary consultation for trachea or need for oxygen in premature infants who
bronchomalacia required oxygen at 28 days
• Sweat chloride testing for patients with recur- –– On reassessment at 36 weeks postmen-
rent wheezing and who are resistant to treat- strual age:
ment is recommended ◦◦ Mild: On room air
• Ribavirin should not be used routinely in the ◦◦ Moderate: FIO2 < 30%
treatment of bronchiolitis ◦◦ Severe: FIO2 > 30% or on positive-pres-
sure ventilation
Prevention
• CXR can present with areas of opacification,
• Palivizumab (Synagis®) 15 mg/kg intramus-
atelectasis, hyper-expansion, and pulmonary
cular (IM) for premature and high-risk infants
edema
as monthly IM monoclonal antibody
• Sequelae of BPD and associated conditions
injection
include:
• Handwashing is best measure to prevent nos-
–– Tachypnea, retractions
ocomial infection
20 Pulmonology 709
–– Suboptimal growth, increased caloric ASTHMA

requirements
–– Dysphagia and GER can lead to aspiration Background
–– Neurodevelopmental delays with cerebral • Heterogeneous disease characterized by
palsy being the most common presentation chronic inflammation of the airways
–– Heart failure secondary to pulmonary hyper- • US prevalence of childhood asthma ranges
tension, ventricular hypertrophy, pulmonary from 10% to 15%
overcirculation from right-to-left shunting • Wheezing observed in about 3% of infants
before 3 years of age
Management • Several asthma phenotypes have been
• Prevention: Good prenatal care, prevention of described based on onset of symptoms and
prematurity natural course of the disease process:
• Postnatal management leading to reduced –– Transient
incidence of BPD: ◦◦ Early onset at < 1 year old
–– Use of gentle ventilation, permissive ◦◦ Decreased lung function at birth
hypercapnia, noninvasive forms of airway ◦◦ Resolved symptoms by mid-childhood
pressure/ventilation ◦◦ No further reductions in pulmonary
–– Assure growth and adequate nutrition function
–– Vitamin A supplementation in extremely –– Nonatopic
low birthweight infants shown to reduce ◦◦ Early onset at < 3 years
incidence of BPD ◦◦ Variable clinical course
–– Screen for and treat for pulmonary –– Late onset
hypertension ◦◦ Onset > 3 years
–– Use of systemic steroids postnatally ◦◦ Variable clinical course
decreases risk of BPD and improves extuba- –– Persistent
tion success. However, routine use is con- ◦◦ Early onset < 3 years
traindicated due to increase in long-term ◦◦ Abnormal lung function by 3 years
risk of neurodevelopmental impairment ◦◦ Most patients are atopic
• Management once BPD diagnosed: • Asthma symptoms are more common in boys
–– Multidisciplinary follow-up of neurodevel- before puberty, but more severe in girls after
opmental, cardiovascular, and nutritional puberty
sequelae • The asthma predictive index was developed
–– Bronchodilators, inhaled steroids, diuretics to help predict which children would be likely
are frequently used to develop persistent asthma symptoms
–– Insufficient data related to long-term –– Its negative predictive value is better than
outcomes its positive predictive value
–– Short course of steroids for acute –– Positive if:
exacerbations ◦◦ 1 or more major risk factors: Parental
–– Prevent infections; prophylaxis with palivi- history of asthma, atopic dermatitis, sen-
zumab decreases frequency of RSV-related sitization to aeroallergen
hospitalizations
OR Table 20.2 Differential diagnosis for asthma

◦◦ 2 or more minor risk factors: Sensitiza Red flags Possible diagnosis
tion to food, more than 4% eosinophilia, Sudden onset of symptoms, Foreign body aspiration
wheezing apart from upper respiratory witnessed choking, localized
wheezing
tract infections Coughing and choking when Dysphagia with aspiration
eating or drinking
Pathophysiology Sneezing, cough, nasal Chronic upper airway
• Inflammation plays a key role in asthma congestion cough syndrome
pathophysiology Poor growth and low BMI Cystic fibrosis,
• Important contributors to the inflammatory immunodeficiency
Chronic rhinorrhea, recurrent Cystic fibrosis, primary
response include: sinusitis, early-onset ciliary dyskinesia
–– Cell types including lymphocytes, eosino- respiratory symptoms
phils, mast cells, neutrophils, macro- Acute-onset dyspnea and/or Vocal cord dysfunction
phages, smooth muscle cells, and epithelial stridor in teens
cells Chronic wet productive Bronchiectasis
cough, recurrent infections
–– Inflammatory mediators such as IL-5, IL-4, Recurrent pneumonia Immunodeficiency,
and IL-13 anatomical abnormality
• IgE plays an important role in activation and Chronic wet cough, Vascular ring,
maintenance of allergic disease difficulties feeding, early tracheoesophageal fistula,
onset, noisy breathing tracheomalacia
–– Early-phase reaction or Type I IgE-
Heart murmur, poor weight Congenital heart disease
mediated reactions occur within minutes of gain, cyanosis with feedings
an allergen-related trigger Prematurity, prolonged Bronchopulmonary
◦◦ Cells (such as mast cells) release pre- mechanical ventilation or dysplasia
formed inflammatory mediators that can supplemental oxygen
lead to vasodilation, edema, broncho-
constriction, and increased airway Assessment
mucus secretion • There is no diagnostic test for asthma
◦◦ Early airway obstruction occurs, in addi- • Diagnosis is based on constellation of clinical
tion, there is activation of leukocytes, symptoms including presence of airflow limi-
which in turn leads to late-phase IgE- tation that is at least partially reversible
mediated reactions • Exclusion of alternative diagnoses
–– A late-phase IgE-mediated reaction fol- (Table 20.2)
lows 2–12 h later • Assess for associated comorbidities, includ-
◦◦ Characterized by persistent obstruction ing obesity, GER, rhinitis/sinusitis, depres-
and mucus hypersecretion sion, anxiety, sleep-disordered breathing, and
◦◦ The late reaction is the consequence of allergic bronchopulmonary aspergillosis
inflammatory mediators • Typical symptoms:
• Respiratory infections –– Wheezing, chest tightness, shortness of
–– Viral respiratory infections are the most breath, cough
common trigger of exacerbations in chil- –– Symptoms are usually worse at night and
dren (especially those < 10 years) and have early morning
been associated with future development – – The more symptoms, the more likely the
of asthma diagnosis
–– Bronchiolitis associated with RSV and rhi- – – If cough only symptom or chronic sputum
novirus in early childhood increases risk of production reported, broaden your
developing asthma differential
20 Pulmonology 711
• Common triggers: Table 20.3 Asthma classification

–– Respiratory infections (especially viral Daytime symptoms/
infections) SABA use Activity limitation
–– Exercise Severity Nighttime symptoms Pulmonary function
–– Inhaled allergens (e.g., pollen, pet expo- Intermittent
0–4 years ≤ 2 days/week None
sure, dust mites, cockroaches, mold)
0 nights/month
–– Irritants (tobacco smoke, air pollution) 5–11 years ≤ 2 days/week None
–– Medications (e.g., nonsteroidal anti- ≤ 2 nights/month FEV1 > 80%; FEV1/
inflammatory medications, beta-blockers) FVC > 85%
–– Changes in weather 12– ≤ 2 days/week None
• Physical findings and objective data: 19 years ≤ 2 nights/month FEV1 > 80%; FEV1/
FVC > 85%
–– Wheezing on exam, especially on forced Mild persistent
exhalation; signs of atopy such as allergic 0–4 years 3–6 days/week Minor limitation
shiners, rhinitis, or eczema 1–2 nights/month
–– PFT 5–11 years 3–6 days/week Minor limitation
◦◦ Spirometry measurements before and 3–4 nights/month FEV1 > 80%; FEV1/
FVC > 80%
after bronchodilator recommended in 12– 3–6 days/week Minor limitation
the assessment of patients ≥ 5 years/o 19 years 3–4 nights/month FEV1 > 80%; FEV1/
▪▪ Look for obstruction on spirometry FVC > 85%
▪▪ Use bronchodilator response to assess Moderate persistent
0–4 years Daily Some limitation
reversibility
3–4 nights/month
▪▪ Decline in lung function (FEV1 and 5–11 years Daily Some limitation
FEV1/FVC ratio) can usually be seen > 1 night/week FEV1 60–80%; FEV1/
in those with symptoms starting FVC 75–80%
< 3 years and is noted by 6 years 12– Daily Some limitation
19 years > 1 night/week FEV1 60–80%; FEV1/
–– Exercise challenge can be used to evaluate
FVC 80–85%
for exercise-induced asthma Severe persistent
◦◦ Baseline spirometry obtained prior to 0–4 years Daily Extremely limited
treadmill challenge > 1 night/week
◦◦ Spirometry obtained after exercise to 5–11 years Throughout the day Extremely limited
Often FEV1 < 60%; FEV1/
document drop in pulmonary function FVC < 75%
–– CXR 12– Throughout the day Extremely limited
◦◦ May show hyperinflation, peribronchial 19 years Often FEV1 < 60%; FEV1/
wall thickening, atelectasis FVC < 80%
◦◦ Most helpful to evaluate for differential SABA short-acting beta-2 agonist, FEV1 forced expiration
causes of symptoms volume in 1 s, FVC forced vital capacity
–– Allergy testing
◦◦ Skin testing or serum testing may help in –– Impairment: Relates to the frequency and
identifying sensitization to inhaled intensity of symptoms, how the disease
perennial allergens affects day-to-day function
–– Risk estimates likelihood of exacerbations
Asthma classification or having reduced lung function
• Severity is best assessed prior to initial con-
troller therapy (Table 20.3) Exercise-Induced Asthma (EIA)
• Assess components of severity: impairment • Clinical presentation of EIA
and risk
–– Shortness of breath, coughing, wheezing, uncontrolled symptoms, and at least every

chest tightness, or pain associated with 1–2 years
physical activity. Can present in isolation • Increased risk of exacerbation if 1 or more:
or associated with symptoms of poorly –– Uncontrolled asthma symptoms, increased
controlled asthma use of SABA, inadequate dose or use of
–– Symptoms present during or minutes after ICS, < 60% FEV1, psychological and/or
exertion, peak after 5–10 min of exercise, socioeconomic barriers, comorbidities,
and improve within 20–30 min eosinophilia, exposure to known triggers,
–– Usually self-limited but may result in a history of pediatric intensive care unit or
severe asthma attack intubation, ≥ 1 severe exacerbation in the
• Management of EIA last year
–– Warm-up period 15 min prior to exercise • Consider step-down in therapy if asthma
and wearing scarf/mask may reduce under good control for at least 3 months
symptoms
–– In 80% of patients, short-acting beta-ago- Education:
nists (SABAs) before exercise prevent • Self-management education (patient and
symptoms for about 2–3 h families) key in individual asthma control
–– Montelukast can lead to decrease in bron- and improve outcomes
chospasm in about 50% of patients, but • Provide asthma action plan that provides
onset of action is several hours after guidance in daily management as well as plan
administration of care for worsening symptoms
Management of asthma Control environmental factors and comorbidities:

• Assess for allergen exposures either by skin
Assessment and monitoring: testing or serum testing and correlate with
• After initial diagnosis: Review response to medical and exposure history
therapy, reassess severity and control, adjust • Patients should reduce exposure to allergens,
therapy to reduce impairment and risk irritants, and pollution to which they are sen-
• Periodic reassessment recommended due to sitized or have a reaction
variable nature of asthma • Assess for and control comorbidities associ-
• Annual increase in asthma exacerbations seen ated with increased risk for poor control:
in September Obesity, allergic rhinitis/sinusitis, allergic
• Reassess patients every 2–6 weeks initially to bronchopulmonary aspergillosis, OSA,
gain disease control and then every depression, and other psychosocial factors.
1–6 months
• Assess frequency of daytime symptoms, Medications:
nighttime symptoms, and reliever use over • Initial treatment based on severity category
the past month (Table 20.4)
• Can use asthma control tools such as the • On reassessment of asthma control, adjust
Asthma Control Test (ACT) or Asthma therapy regardless of initial severity
Control Questionnaire (ACQ) as part of classification.
assessment
• Evaluate technique and compliance with con- Beta-2 agonists
troller therapy • Relieve airway constriction by binding to
• PFT at initial assessment, after treatment and receptors on airway smooth muscle
stabilization of symptoms, during periods of • Frequent use can signal poor asthma control
20 Pulmonology 713
Table 20.4 Asthma: Initial controller therapy

Preferred initial
≥ 6 years Preferred initial therapy ≤ 5 years therapy
Intermittent asthma Step 1 Infrequent viral wheezing and no Step 1
symptoms SABA as needed symptoms in between episodes SABA as needed
Consider
intermittent ICS
Persistent symptoms or Step 2 Uncontrolled asthma symptoms, > 3 Step 2
high-risk factor for Low-dose ICS exacerbations/y or consider trial in Daily low-dose
exacerbations those with frequent wheezing (every ICS
6–8 weeks)
Asthma symptoms/SABA Step 2 Uncontrolled asthma on low-dose ICS Step 3
use > 2X/week Low-dose ICS Double low-dose
Consider LRTA ICS
Asthma symptoms most Step 3 Uncontrolled asthma on double low Step 4
days or waking > 1X/ Medium-/high-dose ICS or if dose Refer to specialist
week ≥ 12 years, low-dose ICS/ Add LTRA
LABA Add intermittent
ICS or increased
ICS frequency
Severe initial presentation Step 4
(uncontrolled asthma or Short OCS course AND
acute exacerbation) High-dose ICS or if ≥ 12 years,
moderate dose ICS/LABA
Uncontrolled asthma after Step up therapy or use adjunct
initial therapy therapies
Step 3: Can add LTRA to
low-dose ICS
Step 4: Can add ipratropium (if
> 12 years) to ICS or add
LTRA to high-dose ICS
Step 5: Refer to specialist for
add-on therapy (e.g.,
tiotropium, anti-IgE, anti-IL-5,
low-dose OCS)
Adapted with modifications from Global Initiative for Asthma Report [1]
SABA short-acting beta-2 agonist, ICS inhaled corticosteroid, LRTA leukotriene receptor antagonist, LABA long-acting beta-2
agonist, OCS oral corticosteroid
• Short-acting beta-2 agonists (SABA) Inhaled corticosteroids

–– Onset of action is within 15 min, but of • Most potent and effective medication for
relatively short duration (3–4 h) long-term control of asthma
• Long-acting beta-2 agonists (LABA) • Decrease airway inflammation and bronchial
–– Effects can last at least 12 h hyperresponsiveness, relieve asthma symp-
–– Used in combination with ICS toms, and improve lung function
• Adverse effects • Patients should rinse and spit out after
–– Agitation, irritability, tremors, tachycardia, inhalation
insomnia, arrhythmias; higher doses used • Adverse effects
during acute asthma exacerbations can lead –– Oral thrush, oral absorption, and higher-
to hypokalemia or hypoglycemia dose ICS use may lead to decrease in
growth velocity and adrenal suppression
Leukotriene receptor antagonists PNEUMONIA

• Block leukotriene, which acts as a potent
mediator leading to bronchoconstriction, vas- Background
cular permeability, and increased mucus pro- • Lower respiratory tract infection with fever
duction and activates inflammatory cells and respiratory symptoms with parenchymal
• Usually an add-on therapy and not preferred involvement on exam or by CXR findings
treatment option in mild persistent asthma • Streptococcus pneumoniae is the most com-
• Adverse effects mon bacterial cause in children older than
–– Generally, well tolerated, but associated 1 week of age
with upper respiratory tract infection, • Viruses account for 14–35% of cases
fever, headache, sore throat, behavior/ • Complicated pneumonia with empyema and
mood-related changes necrosis
• Community-associated methicillin-resistant
Acute asthma exacerbations Staphylococcus aureus
• Patients present with acute or subacute wors-
ening from baseline symptoms and/or pulmo- Most common causes of pneumonia by age
nary function group
• Brief initial assessment should concentrate • Neonates (0–3 m)
on time of onset and possible triggers, sever- –– Group B strep and Gram-negative bacteria
ity compared to previous exacerbations, –– Early and late onset
recent use of asthma medications, and associ- –– Early onset—first 3 days of life with respi-
ated cardiorespiratory process ratory distress
• Severe exacerbation presentation: shortness • Three weeks to 3 months
of breath, inability to speak in full sentences, –– Chlamydia trachomatis
sitting hunched, agitated, accessory muscle ◦◦ Interstitial infiltrate on CXR
use, tachypnea and tachycardia, pulsus para- –– RSV and parainfluenza
doxus > 20 mmHg, SpO2 < 92% (after an ◦◦ Bronchiolitis or pneumonia
hour of therapy is a good predictor for hospi- –– Streptococcus pneumoniae
talization needs), PEF < 40% baseline ◦◦ Major cause of pneumonia through
• Life-threatening exacerbations can present childhood
with silent chest, drowsiness, or confusion –– Bordetella pertussis
• CXR not recommended routinely, but patient ◦◦ Tracheobronchitis with severe parox-
can present with atelectasis, which needs to ysm, usually no fever
be clinically differentiated from pneumonia • Three months to 5 years
• Therapy for acute exacerbations: –– Most common etiology—viruses (RSV,
–– Oxygen as needed to keep SpO2 > 90% parainfluenza, human metapneumovirus,
–– Three SABA treatments spaced every influenza, and rhinovirus)
20–30 min –– Strep pneumonia—most treatable
–– Adding high doses of ipratropium bromide pathogen
leads to decreased rate of hospitalization –– Mycoplasma pneumoniae
–– Systemic corticosteroids to patients with ◦◦ Increased incidence in children
moderate to severe exacerbations or with approaching school age
poor initial response to SABA • Five years to adolescence
20 Pulmonology 715
–– Most common cause • Findings on exam may be dullness to percus-

◦◦ Atypical organisms such as Mycoplasma sion, crackles, decreased breath sounds, and
and Chlamydophila pneumoniae bronchial breaths
▪▪ Mycoplasma—leading cause of pneu- • In the absence of fever, tachypnea, increased
monia in school-age children and work of breathing, or auscultatory abnormali-
young adults ties, bacterial pneumonia is unlikely
Most common causes of pneumonia by geo- Diagnosis

graphic location • Clinical diagnosis as above
• Histoplasmosis • Rapid influenza test may help to identify the
–– Ohio and Mississippi River Valleys and cause of fever and to reduce unnecessary use
Caribbean of antibiotics
• Coccidioidomycosis • CBC, chemistry, or serology will not help in
–– California, Arizona, and New Mexico identifying etiology or aid in management
• Blastomycosis • Blood culture rarely helpful (only 10% of the
–– Ohio, Mississippi River Valleys; Great time organism is recovered)
Lakes states • ESR and C-reactive protein (CRP) may be
• Legionella elevated but are not specific
–– Infected water worldwide • Tuberculin test if there are TB risk factors or
• Avian influenza TB is being considered
–– Southeast Asia • CXR (Fig. 20.3)
Pneumonia via animal vectors

• Tularemia
–– Rabbits and ticks
• Psittacosis
–– Birds and parakeets
• Q fever
–– Sheep, cows, and goats
Pneumonia with associated exanthems

• Varicella
–– Human to human airborne droplets
• Measles
–– Human to human droplets
• Nonspecific signs and symptoms
• Cough and fever—hallmark symptoms
• Tachypnea is the most sensitive and specific
sign of pneumonia
• Most children with cough and fever do not
have pneumonia
• Tachypnea, retractions, wheezing, nasal flar-
ing, grunting, apnea, and abdominal pain may
be presenting or associated symptoms
• Grunting may be a sign of impending respira- Fig. 20.3 A 9-year-old female presents with cough and
tory failure in younger patients/infants fever. Chest radiograph shows right upper lobe infiltrate.
–– A CXR will not change clinical manage- ◦◦ Consider empyema, bacterial resistance,
ment for patients being treated as and nonbacterial pneumonia (FB, CF,
outpatient pulmonary sequestration, bronchiolitis
–– Afebrile children do not need a CXR obliterans, aspiration, and hypersensitiv-
–– CXR always lags behind clinical response. ity pneumonitis)
No need to obtain to confirm response to
antibiotics
–– Obtain a CXR if: BRONCHIECTASIS
◦◦ Complicated pneumonia is being
considered Background
◦◦ Clinical deterioration • Destruction of the airway wall (bronchi and
◦◦ Prolonged fever with no obvious source bronchioles) leads to loss of integrity of the
of infection muscular and elastic layers of the bronchial
◦◦ Abdominal pain with normal appendix wall, results leading to dilated and collapsible
airway
Management
• National guideline for antibiotic initiation Clinical presentation
with community-acquired pneumonia: • Productive cough is most common symptom
–– High-dose amoxicillin (80–90 mg/kg/day) • Dyspnea, rhinosinusitis, and hemoptysis are
for uncomplicated cases being treated as less common
outpatient • Crackles, wheezing, and rhonchi are often
–– Augmentin or cefuroxime as outpatient, if heard; digital clubbing may be present
resistant
–– School age or > 5 years of age azithromycin Differential diagnosis
to cover for Mycoplasma • CF is the most common cause of bronchiecta-
• Indication for hospitalization: Suspected sepsis in pediatric patients in the USA.
sis, severe dehydration, toxic appearance, • Impaired mucociliary clearance (CF and cili-
hypoxemia (SpO2 < 90%), unresponsive to ary dyskinesia)
outpatient therapy, inability to drink • Infections (Mycobacterium tuberculosis,
–– Intravenous fluids and O2, if needed, and Pseudomonas, adenovirus)
antibiotics • Immunodeficiency syndromes
–– Consider blood culture, CXR, chemistry • Immune-mediated (connective tissue dis-
profiles, and CBC eases), allergic bronchopulmonary aspergil-
–– If inpatient: Cefuroxime, ceftriaxone, or losis (ABPA), inflammatory bowel disease
cefotaxime are the antibiotics of choice (IBD)
–– Adolescents: Fluoroquinolones (levofloxa- • Airway injury (chronic aspiration, inhalation
cin, gatifloxacin, moxifloxacin) may be of toxic fumes, hot gases)
used for atypical pneumonia • Congenital or connective tissue abnormalities
–– If Staphylococcus is considered, add (yellow nail, Marfan syndrome, alpha-1 anti-
clindamycin or vancomycin trypsin deficiency, airway cartilage defi-
–– Uncomplicated pneumonia responds to ciency, tracheobronchomegaly, Young
antibiotics in 48–96 h syndrome)
–– If no response or persistent pneumonia • Obstructed airways (retained FB, intralumi-
◦◦ Repeat CXR nal masses, extraluminal compression)
20 Pulmonology 717
Evaluation • CF transmembrane regulator (CFTR) dys-

• PFT may show obstruction, restriction, or function/absence leads to:
both, depending on etiology and severity –– Excessive reabsorption of sodium and defi-
• CXR may reveal airway dilation, increased cient chloride secretion
pulmonary markings with “tram tracking” –– Passive movement of water is decreased,
(thickening of the bronchial walls), and areas and airway secretions are dehydrated with
of atelectasis very low surface liquid layer
• High-resolution CT scan is the gold standard –– Cilia become compressed, inhibiting cili-
and reveals detailed anatomy of the bronchial ary clearance and cough clearance
tree –– Bacteria thrive, and the immune function at
• There is a lack of airway tapering with lumi- the airway surface is also abnormal
nal dilation, bronchial wall thickening, hon- –– Repeated bacterial infection leads to air-
eycombing, and mucous plugging way damage and bronchiectasis in the lung
◦◦ CFTR dysfunction leads to dysfunction
Management and prognosis in other organ systems:
• Determining the primary cause is of critical ▪▪ Organ systems primarily involved:
importance and is best done with direction respiratory, GI, genitourinary, and
from pediatric pulmonologist integumentary (sweat glands)
• Evaluation may include swallow study, sweat • There are > 1700 mutations in the CFTR
chloride testing, and bronchoscopy protein
• Mucus clearance should be enhanced with • Different classes of mutations result in differ-
hypertonic saline nebulization, inhaled muco- ent levels of CFTR function/production, thus
lytics, and chest physiotherapy variable clinical presentation
• ICS can reduce airflow obstruction • The most prevalent mutation is F508 deletion
• Chronic macrolide therapy has been found to (F508del), associated with both pulmonary
be as beneficial as anti-inflammatory drugs disease and pancreatic insufficiency
• Culture should be obtained –– 85% of the US population have one copy
• Aggressive treatment of Pseudomonas and
Staphylococcal infections is indicated, but Clinical presentation
antimicrobial therapy should be targeted to • Pulmonary manifestations
specific pathogens –– Cough is most common and consistent
• If bronchiectasis is localized and severe, symptom. Often productive but can also be
lobectomy is a last resort in cases without dry
systemic etiology –– Increased anteroposterior (AP) diameter of
the chest due to hyperinflation associated
with airway obstruction
CYSTIC FIBROSIS –– Hyperresonance, diffuse or localized
crackles
Background –– Nasal obstruction, nasal polyps, recurrent
• Autosomal recessive inheritance pattern due to sinusitis
a mutation on the long arm of chromosome 7 –– Clubbing
• Highest incidence in Caucasians, highly –– In advanced disease: Cyanosis, exercise
prevalent in Latinos and African Americans. intolerance, shortness of breath, growth
Less frequently seen in Asians and Native failure, respiratory failure, and death
Americans
–– Common bacterial pathogens include • Integumentary manifestations

Staphylococcus aureus and Pseudomonas –– Excessive salt loss in sweat predisposes
aeruginosa children to hyponatremia, particularly
–– Multidrug-resistant organisms are becoming when hot or exercising
more common (MRSA, Stenotrophomonas – – Hypochloremic alkalosis and dehydration,
maltophilia, and Burkholderia cepacia especially in hot environments, can be
complex). deadly in infants
• Gastrointestinal manifestations
–– Meconium ileus is seen in up to 20% of Complications
newborns with CF • Distal intestinal obstruction syndrome
–– Characterized by abdominal distention, (DIOS)
emesis, and failure to pass meconium in –– More commonly seen with poor enzyme
the first 24–48 h adherence, also in those with a history of
–– Abdominal radiograph (KUB) shows air meconium ileus
fluid level with ground glass-appearing –– Fecal material accumulates in the terminal
material in the central abdomen portion of the ileum and cecum
–– Gastrografin enema diagnostic and – – Osmotic agents such as polyethylene gly-
therapeutic col (MiraLAX®) are helpful
–– Can give hyperosmolar contrast as well –– Can also give enemas and other stool soft-
–– May need to consider surgery if medical eners as an adjunct
management fails –– If severe or complete obstruction, can require
–– Pancreatic-insufficient (PI) patients will Gastrografin enema to relieve obstruction
progress to complete or almost complete • Rectal prolapse
disruption of pancreatic acini and replace- –– Due to combination of intestinal disease
ment with fibrous tissue. Lack of endoge- and poor supporting musculature from
nous digestive enzymes causes fat poor nutrition
malabsorption –– Evidence of recurrent rectal prolapse in
◦◦ Symptoms: Frequent, loose, foul smell- otherwise healthy children is an indication
ing, and greasy stools, flatus, and poor for sweat chloride testing to assess for CF
weight gain • Nasal polyps
◦◦ PI also associated with fat-soluble vita- –– Most prevalent in teens and young adults
mins (ADEK) deficiency –– Local steroids and nasal rinses can be of
▪▪ Deficiencies can cause night blind- benefit for symptom control
ness, decreased bone density, and –– If there are nasal obstructive symptoms
neurologic dysfunction (neuropathy, such as chronic rhinorrhea, snoring, and
dementia) sinus pain or pressure, surgical interven-
• Genitourinary manifestations tion is warranted
–– Pubertal development is often delayed, – – Even with surgical resection, polyps are
particularly if nutrition is poor likely to return
–– Females have decreased fertility related to • CF-related liver disease
thick cervical mucus –– Found in 2–3% of cases
–– Many females with CF carry pregnancies –– More common in those with severe muta-
to term, without detriment to lung tions with little CFTR function
function – – Mainstay of treatment is to prevent ongo-
–– > 95% of males are infertile due to absence ing liver damage and associated complica-
or atretic vas deferens tions of portal hypertension and cirrhosis
20 Pulmonology 719
• CF-related diabetes • DNA testing can confirm and, when sequenc-

–– Most common comorbidity ing is sent, will identify > 95%
–– Affects 20% of adolescents and up to 40% • Pancreatic function testing
of adults –– Pancreatic fecal elastase preferred
–– Shares features of both Type I and Type II –– Can assess fecal fat but much less
diabetes but is a distinct entity accurate
–– Primarily caused by insulin insufficiency,
but fluctuating insulin levels also play a Management per CF Foundation Guidelines
part • Centers of care: Care is managed in a net-
–– Often clinically silent, screen with oral work of multidisciplinary centers.
glucose tolerance test (OGTT) annually • Visits: Infants seen monthly for follow-up
after age 10 years until age 1 and then quarterly
• Imaging:
Diagnosis –– CXR done annually, generally demonstrat-
• Newborn screening: ing mucous plugging and central and upper
–– US states use different methods of testing lobe bronchiectasis
–– In most states, initial testing uses immuno- – – May need CXR to evaluate more closely
reactive trypsinogen testing and, if ele- for bronchiectasis
vated, limited DNA testing • PFT via spirometry assessed quarterly start-
–– Confirmatory sweat testing is ing at age 5 years
recommended –– Initially obstructive process, and then with
–– Newborn screening can miss positive increasing lung damage, a restrictive pro-
cases, especially pancreatic sufficient or cess is noted
those with less common mutations. CF • Microbiology
must be a consideration if there are clinical –– Sputum cultures to be assessed a minimum
features 3 times per year
• Sweat chloride is abnormal if > 40 in infant –– First common bacteria noted is
less than 6 months, and > 60 in those older Staphylococcus aureus
than 6 months –– Pseudomonas is next commonly seen and
–– Pilocarpine iontophoresis is used to stimu- treated to eradicate due to potential for col-
late sweating onization and hastening lung damage
–– Positive results should be confirmed with –– Also, commonly seen: MRSA,
genetic testing Stenotrophomonas maltophilia
–– Negative results with high clinical suspi- –– Low prevalence but primarily seen in CF:
cion should also have genetic testing Burkholderia cepacia
–– False-positive sweat chloride can occur:
◦◦ If testing is completed on skin affected Primary goals of management
by eczema or contaminated with lotion • Maintain lung function as close to normal as
◦◦ Hypothyroidism possible.
◦◦ Skin disorders • Mainstay therapies include hydration of air-
◦◦ Untreated adrenal insufficiency way surface layer with hypertonic saline, liq-
◦◦ Nephrogenic diabetes insipidus uefying mucus with use of dornase alfa, and
◦◦ Hypoparathyroidism clearance of airways using various ACTs
◦◦ Severe malnutrition • Prevent infections by limiting exposure to
other CF patients and other reservoirs of
infection (freshwater lakes, humidifiers, hot • Surgical intervention required

tubs) –– Meconium ileus
• Treat infections when present with directed –– Intussusception
antimicrobial therapy –– Gastrostomy tube placement
• Ensure adequate nutrition through high-calo- –– Rectal prolapse
rie diet, appropriate enzyme supplementa-
tion, and close monitoring of growth CF care across the life span
• Transition to adult care is a requirement of all
Managing complications accredited CF centers
• Mild acute exacerbation treatment –– There is often formal preparation for
–– Increased inhaled bronchodilator therapies patients 18–21 transitioning to adult care
and mucolytics • Median survival is currently 37 years
–– Increased ACTs • Infants now born with CF and who are cared
–– Usually oral antimicrobials for in an accredited CF center will likely sur-
• Moderate and severe pulmonary vive beyond age 50
exacerbations
–– Usually require hospital admission for IV
antibiotics PRIMARY CILIARY DYSKINESIA
–– Aggressive respiratory therapies
–– May require additional nutritional inter- Background
vention to maintain adequate growth dur- • Autosomal recessive disorder with extensive
ing illness genetic heterogeneity
• Characterized by dysmotile, immotile, or
Standard therapies for treatment in CF absent cilia
• Pancreatic enzyme replacement orally • The ciliary defects lead to abnormal muco-
• Multivitamins (particularly fat-soluble ciliary clearance
vitamins)
• Bronchodilators Clinical presentation
• Hydrating agents (7% hypertonic saline) • Symptoms in organs where ciliary motility is
• Mucolytics (dornase alfa) important for normal function
• Antibiotics (inhaled, oral, or IV) –– Neonatal respiratory distress or neonatal
• ACT/chest physiotherapy (CPT) pneumonia (frequently misdiagnosed as
–– Oscillating chest compression vest transient tachypnea)
–– PEP (positive expiratory pressure) –– Recurrent pneumonias and bronchiectasis
devices –– Recurrent wheezing frequently diagnosed
–– Autogenic drainage as asthma
–– Directed coughing, huff coughing –– Chronic persistent rhinosinusitis
• Anti-inflammatory agents –– Nasal polyps and recurrent otitis media;
–– Azithromycin recurrent otitis media may begin in
• Insulin for CF-related diabetes neonates
• CFTR modulator drugs to improve ion –– Men are infertile and women have
transport decreased fertility
–– Ivacaftor; ivacaftor/lumacaftor; ivacaftor/
tezacaftor Diagnostic evaluation
• Lung transplant indicated for severe and end- • Gold standard: Cilia from nose or trachea by
stage lung disease brushings or mucosal biopsy for evaluation of
20 Pulmonology 721
ciliary abnormalities on electron microscopy • Decreased to absent breath sounds, pleural

(absent, abnormal dynein arms, radial spokes, rub with smaller collection of fluid
doublet arrangements) • Egophony
• Genetic testing—need two mutations in a sin- • Dullness to percussion
gle gene for diagnosis. Problematic due to • Midline shift
heterogeneity, and inability to identify two
mutations does not rule out diagnosis Diagnosis and management
• CT scan • Transudate: Clear or straw colored; low pro-
–– Sinuses: Paranasal sinuses involvement tein and lactate dehydrogenase (LDH)
–– Chest: Bronchiectasis • Exudate: Straw colored or cloudy
–– Pleural fluid/serum protein ≥ 0.5
Management –– Pleural fluid/serum LDH ≥ 0.6
• ACT, antibiotics for infections documented –– Pleural fluid LDH > 2/3 of the upper limit
on culture with sensitivities, ENT evaluation of normal for serum LDH
for surgery if needed • Appearance:
–– Purulent fluid—infection
–– Thin white milky fluid—chyle
EXTRAPULMONARY –– Blood—trauma or malignancy
RESPIRATORY CONDITIONS • CXR—opacification of thorax, blunted cos-
tophrenic angles (Fig. 20.4)
Pleural Effusion –– Decubitus views helpful if fluid is
free-flowing
Background
• > 10 mL fluid in the thoracic cavity
• Due to excessive filtration or defective
absorption
• Normal fluid balance
–– 0.1–0.2 mL/kg of sterile colorless fluid
–– Ninety percent filters from arterial capillar-
ies, reabsorbed at venous capillaries
–– About 10% returned via lymphatic
–– Normal pleural fluid (0.3 mL/kg)
• Etiologies
–– Pneumonia is the most common
–– Neonatal period: Chylous effusion most
common
–– Others: Malignancy, renal disease, trauma,
congestive heart failure, and systemic
diseases
• Suspect in any child with worsening
pneumonia
• Respiratory distress, tachypnea, cough, chest
Fig. 20.4 Chest radiograph of a 2-year-old child with left
pain with pleural inflammation pleural effusion
• Ultrasound helpful to evaluate for • Point of maximal impulse shifts due to displace-
loculations ment of intrathoracic organs to the opposite side
• CT scan for complicated effusions/empy-
ema to define pulmonary and fluid Diagnosis
characteristics • CXR
• Thoracentesis –– Upright, if possible
–– Routine thoracentesis not recommended –– Expiratory films accentuate the contrast
–– Perform thoracentesis to relieve dyspnea between lung markings and the clear area
for large effusions, worsening symptoms, of the pneumothorax
sepsis, or a lack of improvement in symp- • Recurrence rate is high after primary sponta-
toms despite administration of broad-spec- neous pneumothorax
trum antibiotics for diagnostic purposes
• Oxygen for hypoxemia Management
• Consultation with experts as needed • Small pneumothorax < 5% may resolve
spontaneously
• If > 5% of pneumothorax or collapse, or if
Pneumothorax recurrent or under tension, a chest tube for
drainage is necessary
Causes • Pneumothoraces complicating CF frequently
• Primary spontaneous pneumothorax recur, and definitive treatment may be justi-
–– Occurs without trauma or underlying cause fied with the first episode
–– More frequently in tall, thin males, likely • One means of definitive therapy is sclerosing
related to subpleural blebs with doxycycline (chemical pleurodesis)
–– Family history is positive in many • Video-assisted thoracic surgery is preferred
patients therapy for blebectomy, pleural stripping,
–– Usually occurs at rest, but can be precipi- pleural brushing, and instillation of scleros-
tated by air travel in an unpressurized cabin, ing agents over open thoracotomy
weight lifting, and Valsalva maneuver • Extensive pleural adhesion and aggressive
• Secondary pneumothorax pleural stripping may interfere with lung
–– Related to an underlying lung issue transplant potential in the future, an issue that
(asthma, CF, necrotizing pneumonia, inter- must be discussed with the family
stitial lung disease)
–– Trauma (blunt trauma)
–– Loud music (air pressure) Pneumomediastinum
–– Catamenial pneumothorax (unusual condi-
tion associated with menses due to passage Background
of intra-abdominal air through a diaphrag- • Can be traumatic or spontaneous
matic defect) • Spontaneous pneumomediastinum occurs
when air leaks through small alveolar rupture
Clinical presentation to the surrounding bronchovascular sheath
• Onset is abrupt, and the severity depends on • Less commonly, occurs with air escaping
degree of lung collapse from the upper respiratory tract, intrathoracic
• In simple pneumothorax, the lung collapses airways, or esophageal rupture
up to 30% • Triggers: (Most common) asthma exacerba-
• In a tension pneumothorax, patient will be tion and lower respiratory infection; (less
hypoxemic, dyspneic, and possibly common) Valsalva/strenuous lifting and
cyanotic vomiting
20 Pulmonology 723
Clinical presentation Ehlers-Danlos syndrome), neuromuscular

• Chest pain, dyspnea, cough, neck pain, dys- disease (e.g., spinal muscular atrophy)
phagia, odynophagia • Incidence: > 90% of congenital wall
anomalies
Management
• Usually resolves by itself Clinical presentation
• Often noted at birth, may be not associated
with any symptoms
THORACIC DEFORMITIES • Range from asymptomatic to increasing
symptoms in more severe cases
Background –– Exercise intolerance
• Thoracic deformities affect rib cage, spine, –– Fatigue
and respiratory muscles –– Chest pain
• Abnormalities can result in restrictive disease –– Palpitations
due to reduced compliance of chest wall and –– Recurrent chest infections
increased workload/fatigue of respiratory –– Wheezing
muscles –– Stridor
–– Cough
–– Tall and thin
ectus Excavatum (Funnel Chest)
P • Children may experience significant psycho-
(Fig. 20.5) logical stress because of cosmetic
appearance
Background
• 1/400 births, more common in males, rare in Evaluation
African Americans • CXR; increased AP diameter
• Can be isolated, familial, or associated with • CT for Haller index (HI); if significant, should
connective tissue diseases (e.g., Marfan or be repaired
–– HI = lateral internal rib cage dimension/AP
internal sternum to vertebrae dimension
–– Normal value HI: 2.5
–– Surgical repair if HI > 3.25 and/or cardio-
pulmonary involvement
• ECG commonly abnormal; right axis
deviation
• Echo may demonstrate cardiac compression
and mitral valve prolapse
Management
• Based on severity of deformity and physio-
logic compromise
• Mild: Observation and physical therapy to
maintain posture
• Corrective surgery if significant physiologic
Fig. 20.5 Pectus excavatum. A 12-year-old healthy boy
with funnel-shaped chest compromise (Nuss or Ravitch procedure)
Pectus Carinatum (Pigeon Chest) Clinical presentation

• Exertional dyspnea, progressive fatigue in
Background older child
• Anterior displacement of midsternum and • Infants less specific: Poor appetite, failure to
adjacent costal cartilage thrive, diaphoresis, tachypnea, tachycardia,
• Rare: 1/1500 of chest wall deformities and irritability
• Associated with mild to moderate scoliosis, • Syncope, presyncope, and chest pain are fea-
mitral valve prolapse, and coarctation of aorta tures of more advanced disease; hemoptysis
late and sometimes fatal symptom
• Rarely causes limitations Management
• Physical appearance most common • Outcome in pediatrics has improved
complaint • Should be seen by specialist (cardiology or
• HI less than two is significant pulmonology)
• Patients may require a combination of thera-
Management pies, and some patients require surgery
• Surgery for cosmetic and psychological stress (septostomy)
Cor pulmonale
Scoliosis • Right ventricular (RV) hypertrophy leading
to RV failure caused by increased afterload
Background caused by pulmonary hypertension
• Cobb angle = angle from most tilted verte- • Can be caused by chronic lung disease, bron-
brae above and below the apex of the curve chopulmonary dysplasia, cystic fibrosis, arte-
• Scoliosis defined as lateral curvature of the rial hypertension, neuromuscular disease
spine with Cobb angle > 10°
• Curvatures > 50° more likely to be
progressive OBSTRUCTIVE SLEEP APNEA
• Extreme curvatures can lead to respiratory
compromise due to restrictive chest wall
(OSA)
disease Background
• OSA and primary snoring are part of a spec-
Management
trum of sleep-disordered breathing
• Observe for progression
–– Primary snoring = Incidence 12–20%; no
• Bracing
discrete obstructive events or gas exchange
• Spinal fusion for curves > 40°–45°
abnormalities
–– OSA = Prevalence 2–4% in healthy chil-
dren; obstructive apnea and hypopneas
PULMONARY HYPERTENSION often seen with arousals, disturbed sleep,
Background and gas exchange abnormalities
• Mean pulmonary artery pressure of 25 mm • The disorder can occur at any age but is most
Hg or more at rest common in the preschool age group
• Can be caused by left heart disease, lung dis- (2–6 years) and adolescents
ease (including BPD), thromboembolic dis- • A higher prevalence has been reported in
ease, autoimmune disease, variety of other African American and obese children
disease or idiopathic
20 Pulmonology 725
Risk factors and associated conditions • Adenotonsillectomy is first-line therapy and

• Adenotonsillar hypertrophy curative in about 80% of children with OSA
• Obesity • Noninvasive positive airway pressure is an
• Craniofacial abnormalities (such as midface option for poor surgical candidates or those
hypoplasia and micrognathia) with residual OSA after surgery
• Hypotonia (e.g., Down syndrome) • High-risk patients should be monitored as in-
• Neuromuscular disease patients postoperatively
• Cerebral palsy • Patients should be re-evaluated postoperative
to determine if additional treatment is required
• All children should be screened for snoring
• Signs and symptoms that may signal OSA ACUTE LIFE-THREATENING
–– Snoring EVENT (ALTE)/BRIEF RESOLVED
–– Gasping during sleep
–– Enuresis (especially if secondary) UNEXPLAINED EVENT (BRUE)
–– Restless sleeper
Background
–– Unusual positioning during sleep (hyper-
• Common associations with ALTE
extended neck, sleeping propped up)
–– GER disorder most common association
–– Cyanosis
for awake ALTE
–– Sweating during sleep
◦◦ Prevalence of GER in infants with ALTE
–– Morning headaches
as high as 70%
–– Daytime sleepiness in older children
◦◦ Highly symptomatic infants may benefit
–– ADHD-like symptoms, including hyperac-
from therapy with antacids, positional
tivity and/or inattention, difficulty
changes, and thickened feedings
concentrating
–– Neurologic
–– Adenoidal facies as well as signs of atopy
◦◦ Seizures second most common
or nasal congestion
association
–– Chronic mouth breathing with chronic
◦◦ High index of suspicion of child abuse
nasal congestion
important
–– Tonsillar hypertrophy
◦◦ Up to 10% presenting ALTE associated
–– Obesity
with child abuse
–– Failure to thrive
–– Viral respiratory infections
–– Unexplained hypertension
◦◦ RSV most commonly associated ALTE
Management ◦◦ More common in < 2 months, lower
• History and physical exam cannot distinguish birthweight, history of prematurity
between primary snoring and OSA • BRUE now preferred term to more subjective
• Polysomnography diagnostic test of choice ALTE, but terms frequently used
• Complex, high-risk patients (e.g., craniofa- interchangeably
cial disorders, genetic syndromes, neuromus- • BRUE
cular disorders, severe OSA) should be –– < 1 year of age
referred to specialist –– Sudden, brief, and resolved episode with
• Patients with neuromuscular disease may ≥ 1 of the following:
desaturate during sleep but appear well awake ◦◦ Cyanosis or pallor
–– Overnight saturation monitoring may be a ◦◦ Absent, decreased, or irregular
helpful screening tool for sleep-disordered breathing
breathing in these patients ◦ ◦ Change in tone
◦◦ Altered responsiveness ◦◦ Co-sleeping

–– Unexplained after adequate history and ◦◦ Overheating
physical ◦◦ Young maternal age
• Presence of BRUE does not predict SIDS • Increased risk in siblings, but risk of second
Management child death < 1%
• Low-risk BRUE: Patients > 2 months, older • National recommendation on SIDS
preterm infant (> 32 weeks and postconcep- prevention
tual age > 45 weeks), event < 1 min, no previ- –– “Back to sleep”: Supine position. “Tummy
ous events, no need CPR, negative history to play”: Awake and monitored
and exam ◦◦ Marked decline in SIDS rate following
–– Management of low-risk BRUE mass education of this public policy
◦◦ No need for admission –– Firm mattress
◦◦ Workup considered even in low-risk –– Cool ambient air
BRUE –– No soft object or loose bedding
▪▪ Pertussis testing as infants may pres- –– No co-sleeping
ent with few symptoms –– Encourage breastfeeding
▪▪ Pulse oximetry monitoring in the –– No smoking
emergency department –– Sleep in parents’ room for 1st year, but on
▪▪ ECG due to severe outcome associ- separate surfaces
ated with channelopathies –– Pacifiers
–– Has good negative predictive value ◦◦ Use pacifier once breastfeeding has been
–– Observation, further testing, and treatment established
as supported by history and exam ◦◦ Offer pacifier at bedtime or nap time
PEARLS AND PITFALLS
UDDEN INFANT DEATH
S
SYNDROME (SIDS) Diagnostic Testing for Respiratory Conditions
• Factors associated with triple risk model of Interpretation of spirometry

SIDS: • Obstruction: N ↓ FVC, ↓ FEV1, ↓ FEV1/
–– Critical period in development FVC, ↓ FEF 25–75
◦◦ Risk peaks at 2–4 months with most • Restriction: ↓ FVC, ↓ FEV1, N FEV1/FVC, ↓
deaths having occurred by 6 months FEF 25–75
◦◦ Male predominance
Blood gas analysis
–– Infant vulnerability
◦◦ Brain stem dysfunction • Arterial blood gas analysis (see Table 20.1)
• In capillary blood gases, values are compara-
◦◦ Genetic predisposition
◦◦ Defects in arousal ble to arterial pH and pCO2, but pO2 mea-
◦◦ Prematurity, low birthweight surement in CBG is less reliable.
◦◦ Poor prenatal care Chest imaging
–– Environmental factors • Imaging in suspected FB:
◦◦ Prone sleep position –– Get inspiratory and expiratory or bilateral
◦◦ Tobacco smoke exposure decubitus views. May be able to see asym-
◦◦ Soft bedding
20 Pulmonology 727
metric hyperinflation in side with foreign Exercise intolerance

body. • Vocal cord dysfunction: More common in
–– Most foreign bodies are not seen, as they adolescent females. May mimic EIA—need
are radiolucent. to consider if not responding to EIA
treatment
General Signs and Symptoms
Hemoptysis
Stridor/wheezing • Differentiating from hematemesis (vomiting
• Inspiratory—Extrathoracic swelling or blood) and epistaxis (nasal bleeding) can be
obstruction will lead to airway collapse on tricky.
inspiration. Example: Laryngomalacia • Most common reason for symptom usually
• Expiratory—Intrathoracic swelling or not true hemoptysis, but bleeding from upper
obstruction will lead to airway collapse on airway (e.g., nasal bleeding)
expiration. Example: Tracheomalacia
• Biphasic stridor—indicates fixed airflow Congenital airway and pulmonary
obstruction—subglottic space obstruction malformations
• Laryngomalacia: Most common cause of • With symptoms and presenting during
stridor in infants, accounts for up to 75% of infancy, most will require surgical
all causes of stridor intervention.
• Choanal atresia: Infant/newborn in respira-
Acute bronchiolitis
tory distress with inability to pass a 6F cath-
• Most common lower respiratory tract infec-
eter into oropharynx through nose
tion in < 2 years
• Left vocal cord paralysis: Associated with
• Etiology: RSV > 50%
trauma to the recurrent laryngeal nerve at
• Apnea may be more prominent than wheez-
birth or surgical trauma
ing in infants < 2 months or former preterm
• Subglottic hemangioma: 50% accompanied
infants.
by cutaneous hemangiomas of head and neck.
• Peak symptomatology at days 3–4 of illness
Inspiratory or biphasic stridor, which wors-
(“day of illness”)
ens as hemangiomas enlarge
• “Day of illness”: Important variable for pro-
• Viral croup: Course of viral croup in infants
viding anticipatory guidance in outpatient
younger than 1 year of age is prolonged.
management and making decisions regarding
Symptoms often improve during the day with
admission/discharge
recurrence of symptoms in the early hours of
• Routine use of bronchodilators or systemic
the morning.
steroids in management NOT recommended
• Epiglottitis: Stridor is not a prominent
feature. Asthma
• Asthma symptoms are more common in boys
Cough
before puberty, but more severe in girls after
• Nocturnal cough is rare in normal children
puberty.
• Associations: Brassy (tracheal irritation, tra-
• Early-phase reaction or Type I IgE-
cheomalacia); barky (croup); honking (habit
mediated reactions occur within minutes of
cough); staccato (chlamydia, mycoplasma);
an allergen-related trigger.
paroxysmal/whoop (pertussis, CF, FB)
• A late-phase IgE-mediated reaction fol- Thoracic cage deformities

lows 2–12 h later. • Pectus excavatum: > 90% of congenital wall
• Viral respiratory infections (such as RSV and anomalies
rhinovirus) have been associated with future • Scoliosis: Curvatures > 50° more likely to be
development of asthma and are the most com- progressive. Extreme curvatures can lead to
mon trigger of exacerbations in young respiratory compromise due to restrictive
children. chest wall disease.
• All that wheezes is not asthma! Think about
the differential if diagnosis not clear. OSA
• If cough is the only symptom or chronic spu- • Higher prevalence in African Americans and
tum production is reported, broaden your obese children
differential. • Polysomnography diagnostic test of choice
• ICS are the most potent and effective medica- • Adenotonsillectomy is first-line therapy and
tion for long-term control of asthma. curative in about 80% of children with OSA.
• EIA: In 80% patients, SABA before exercise SIDS
prevents symptoms for about 2–3 h. • Peaks at 2–4 months of age, male
• Acute asthma exacerbation: SpO2 < 92% predo m inance
after an hour of therapy is a good predictor • “Back to sleep” supine position for sleep led
for hospitalization need. to marked decline in SIDS rate
Pneumonia Acknowledgment The authors gratefully

• Streptococcus pneumoniae is the most com- acknowledge the contributions of Karen Hardy,
mon bacterial cause in children older than MD, Division of Pulmonary Medicine, Department
1 week of age. of Pediatrics, Stanford Children’s Health Specialty
• Viruses account for 14–35% of cases. Services, Emeryville, California, to the first edi-
• For school-age children needing inpatient tion of this chapter, many of which have been
therapy: Cefuroxime, ceftriaxone, and cefo- incorporated into this edition as well.
taxime are the antibiotics of choice.
Bronchiectasis/cystic fibrosis
• CF is the most common cause of bronchiecta- References
sis in pediatric patients in the USA.
1. Global Initiative for Asthma (2018). Global
• CFTR dysfunction/absence leads to thick
strategy for asthma management and prevention.
secretions, impaired mucociliary clearance,
www.ginasthma.org. Accessed 3 Sept 2018.
recurrent inflammation, and infection, lead-
ing to development of bronchiectasis.
• All US states have newborn screening, but
results are not 100% sensitive. Suggested Reading
• Diagnostic tests include sweat testing and
DNA testing. Alario AJ, McCarthy PL, Markowitz R, Kornguth
• Patients should be managed by a multidisci- P, Rosenfield N, Leventhal JM. Usefulness
plinary team at a CF care center. of chest radiographs in children with acute
• Pneumothorax/pneumomediastinum lower respiratory tract disease. J Pediatr.
–– Pneumothorax > 5% hemithorax will 1987;111(2):187–93.
require chest tube drainage, but pneumo- Al-Qadi MO. Disorders of the chest wall:
mediastinum usually resolves clinical manifestations. Clin Chest Med.
spontaneously. 2018;39(2):361–75.
20 Pulmonology 729
American Academy of Pediatrics Subcommitee Godfrey S. Pulmonary hemorrhage/hemop-

on Diagnosis and Management of Bronchiolitis. tysis in children. Pediatr Pulmonol.
Diagnosis and management of bronchiolitis. 2004;37(6):476–84.
Pediatrics. 2006;118(4):1774–93. Haddad GG, Green TP. Diagnosis approach to respi-
Andabaka T, Nickerson JW, Rojas-Reyes MX, ratory disorders. In: Kliegman RM, Behrman
Rueda JD, Bacic Vrca V, Barsic B. Monoclonal RE, Jenson HB, Stanson BF, editors. Nelson
antibody for reducing the risk of respiratory textbook of pediatrics. 18th ed. Philadelphia:
syncytial virus infection in children. Cochrane Saunders Elsevier; 2007. p. 1731–2.
Database Syst Rev. 2013;(30, 4) Hedges JR, Baker WE, Lanoix R, Field DL. Use of
Baptist E, Kwak J. A 7-month old girl with cya- monitoring devices for assessing ventilation and
notic spells. Pediatr Rev. 2015;36(10):e35–8. oxygenation. In: Roberts JR, Hedges JR, editors.
Bhargava S. Diagnosis and management of com- Clinical procedures in emergency medicine. 4th
mon sleep problems in children. Pediatr Rev. ed. Philadelphia: Saunders; 2004. p. 32–6.
2011;32(3):91–8. Hinds D, Cooper M, Daftary A. Case 1: per-
Butterfield R. Primary ciliary dyskinesia. Pediatr sistent tachypnea in an infant. Pediatr Rev.
Rev. 2017;38(3):e10–2. 2017;30(7):330–2.
Caceres M, Ali SZ, Braud R, Weiman D, Garrett Hofferberth SC, Watters K, Rahbar R, Fynn-
HE Jr. Spontaneous pneumomediastinum: a Thompson F. Management of congenital tra-
comparative study and review of the literature. cheal stenosis. Pediatrics. 2015;136(3):e660–9.
Ann Thorac Surg. 2008;86(3):962–6. Holinger LD. Evaluation of stridor and wheezing.
Cashen K, Petersen TL. Pleural effusions and pneu- In: Holinger LD, editor. Pediatric laryngology
mothoraces. Pediatr Rev. 2017;38(4):170–81. & bronchoesophagology. New York: Lippincott
Chang AB, Glomb WB. Guidelines for evaluat- Raven; 1997. p. 28–41.
ing chronic cough in pediatrics: ACCP evi- Kair LR, Leonard DT, Anderson
dence-based clinical practice guidelines. Chest. JM. Bronchopulmonary dysplasia. Pediatr Rev.
2006;129(1 Suppl):260S–83S. 2012;33(6):255–63.
Cherry JD. Clinical practice. Croup N Engl Med. Kobelska-Dubiel N, Klincewicz B, Cichy W. Liver
2008;358(4):384–91. disease in cystic fibrosis. Prz Gastroenterol.
Cotton RT, Reilly JS. Stridor and airway obstruc- 2014;9(3):136–41.
tion. In: Bluestone C, Stool S, Kenna M, editors. Kovesi T, Rubin S. Long-term complications of
Pediatric otolaryngology. 3rd ed. Philadelphia: congenital esophageal atresia and/or tracheo-
WB Saunders; 1995. p. 1275–86. esophageal fistula. Chest. 2004;126(3):915–25.
Crotty E, Brody AS. Imaging of the respira- LeGrys VA, Yankaskas JR, Quittell LM,
tory system. In: Taussig LM, Landau LI, edi- Marshall BC, Mogayzel PJ Jr, Cystic Fibrosis
tors. Pediatric respiratory medicine. 2nd ed. Foundation. Diagnostic sweat testing: the
Philadelphia: Mosby; 2008. p. 135. Cystic Fibrosis Foundation guidelines. J Pediatr.
DiFranza JR, Aligne CA, Weitzman M. Prenatal 2007;151(1):85–9.
and post-natal environmental tobacco smoke Marcus CL, Brooks LJ, Draper KA, Gozal D,
exposure and children. Pediatrics. 2004;113(4 Halbower AC, Jones J, American Academy of
Suppl):1007–15. Pediatrics. Diagnosis and management of child-
Galli SJ, Tsai M, Piliponsky AM. The devel- hood obstructive sleep apnea syndrome. Clin
opment of allergic inflammation. Nature. Pract Guidel Pediatr. 2012;130(3):576–84.
2008;454(7203):445–54. Matiz A, Roman EA. Apnea. Pediatr Rev.
Global Initiative for Asthma (2018). Global strat- 2003;24(1):32–4.
egy for asthma management and prevention. Mayer OH, Allen J. Chest wall and spinal deformi-
www.ginasthma.org. Accessed 3 Sept 2018. ties. In: Light MJ, editor. Pediatric pulmonol-
ogy. 1st ed. Itasca, IL: American Academy of recurrent or persistent wheezing. Am J Respir
Pediatrics; 2011. p. 309–45. Crit Care Med. 2016b;194(3):356–73.
McBride W. Congenital lesions of the lung. Rosenberg J. Scoliosis. Pediatr Rev.
NeoReviews. Itasca, IL: 2016;17(5):3263–70. 2011;32(9):397–8.
Mindell JA, Owens JA. A clinical guide to pedi- Sahn SA, Heffner JE. Spontaneous pneumothorax.
atric sleep: diagnosis and management of sleep N Engl J Med. 2000;342(12):868–74. Review.
problems. Philadelphia: Lippincott Williams & Schechter M, O’Sullivan B. Cystic fibrosis. In:
Wilkins; 2003. Light MJ, editor. Pediatric pulmonology. 1st ed.
Mueller G, Eigen H. Pulmonary function test- Itasca, IL: American Academy of Pediatrics;
ing in pediatric practice. Pediatr Rev. 2011. p. 717–43.
1994;15(10):403–11. Sharma G, Conrad C. Croup, epiglottitis and bac-
National Heart, Lung, and Blood Institute. National terial tracheitis. In: Light MJ, editor. Pediatric
asthma education program Expert Panel Report pulmonology. 1st ed. Itasca, IL: American
3 (EPR-3). Guidelines for the diagnosis and Academy of Pediatrics; 2011. p. 348–63.
management of asthma. Bethesda: National Shields MD, Bush A, Everard ML, McKenzie S,
Institutes of Health; 2007. (NIH Publication No. Primhak R, British Thoracic Society Cough
08-5846) Guideline Group. BTS guidelines: recommen-
Nevin MA. Pulmonary hemosiderosis. In: dations for the assessment and management
Kliegman RM, Stanton BF, St. Geme III JW, of cough in children. Thorax. 2008;63(Suppl
Schor NF, Behrman RE, editors. Nelson text- 3):iii1–iii15.
book of pediatrics. 19th ed. Philadelphia: Stillwell P. Bronchiectasis. In: Light MJ, edi-
Saunders Elsevier; 2011. p. 1498–500. tor. Pediatric pulmonology. 1st ed. Itasca,
Rajagopal H, Karnik R, Sahulee R. Pediatric IL: American Academy of Pediatrics; 2011.
hypertension. Pediatr Rev. 2016;37(3):129–31. p. 346–75.
Ren CL, Esther CR Jr, Debley JS, Sockrider M, Tieder JS, Bonkowsky JL, Etzel RA, Franklin
Yilmaz O, Amin N, ATS Ad Hoc Committee on WH, Gremse DA, Herman B, Subcommittee on
Infants with Recurrent or Persistent Wheezing, Apparent Life Threatening Events, et al. Brief
et al. Official American Thoracic Society clini- resolved unexplained events (formerly apparent
cal practice guidelines: diagnostic evaluation of life-threatening events) and evaluation of lower-
infants with recurrent or persistent wheezing. Am risk infants. Pediatrics. 2016;137(5):e20160590.
J Respir Crit Care Med. 2016a;194(3):356–73. Weinberger M. Bronchiolitis. In: Light MJ, edi-
Ren CL, Esther CR Jr, Debley JS, Sockrider tor. Pediatric pulmonology. 1st ed. Itasca,
M, Yimaz O, Bazzy-Asaad A, et al. Official IL: American Academy of Pediatrics; 2011.
American Thoracic Society clinical practice p. 377–90.
guidelines: diagnostic evaluation of infants with
Nutrition
21
Susan S. Baker
• Pancreatic exocrine function and bile acid

Abbreviations pool are reduced in the first year of life com-
pared to those in older children and result in a
AI Adequate intake: the recommended aver-
reduced coefficient of fat absorption (% of
age daily intake level based on observed or
absorbed fat from the diet).
experimentally determined approxima-
• After about 1 year of age, pancreatic exocrine
tions or estimates of nutrient intake by a
function and bile acid pool approach adult
group of healthy people that are assumed
characteristics.
to be adequate—used when there is not
enough data to determine an RDA
DRI Dietary reference intake Nutrition Requirements
USDA United States Department of Agriculture Nutrients can be thought of as essential, nonessen-
UL Tolerable upper intake level: the highest tial, and conditionally essential:
average daily intake that is unlikely to • Essential—nutrients that cannot be synthe-
pose a risk of adverse health effects for sized from precursors and hence must be pro-
almost all individuals in the general vided in the diet.
population • Nonessential—nutrients that can be synthe-
RDA Recommended dietary allowance: the sized by the body; thus, an extracorporeal
average daily level of intake of a nutrient source is not required.
sufficient to meet the nutrient require- • Conditionally essential—nutrients that are
ments of 97–99% of healthy people synthesized within the body or that have lim-
ited synthesis under special physiologic
conditions.
GENERAL The nutrients discussed in the following are all

considered essential.
• Digestive enzymes, including disacchari-
dases, peptidases, and acid secretion, are
present and functional by approximately MINERALS
24 weeks of gestation.
Minerals are inorganic substances that are not
made by living things. Minerals are found natu-
rally in soil and water and are absorbed by plants,
S. S. Baker (*) which are then eaten by people and other animals.
Jacobs School of Medicine and Biomedical Sciences, University at
Buffalo, State University of New York, Buffalo, NY, USA Examples of minerals are iron, calcium, and potas-
e-mail: ssbaker@Buffalo.edu

732 S. S. Baker
sium. The USDA lists 14 essential minerals • May need additional salt in very hot climates,
(excluded in the following are manganese and during unaccustomed strenuous physical
molybdenum). activity, during diarrhea, if an ileostomy is
present, especially in young children, and if
suffering from cystic fibrosis
Calcium
• 99% found in teeth and bone hromium
C
• 1% in extracellular fluid, blood, muscle, and
other tissues • Functions in carbohydrate and fat metabo-
• Functions in as follows: lism and to potentiate the action of insulin.
–– Blood clotting • Deficiency is rare; described in 3 patients on
–– Mediating vascular contraction and total parenteral nutrition (TPN) with no chro-
vasodilatation mium content.
–– Muscle contraction • Food sources include as follows:
–– Nerve transmission –– Broccoli, fruits and fruit juice, meats, gar-
–– Glandular secretions lic, basil, whole grains
• Sources:
–– Best sources are dairy, canned fish with
bones (salmon, sardines), and fortified C opper
cereals.
• Deficiency caused by inadequate intake or • Functions as a component of metalloenzymes
malabsorption: that act as oxidases:
–– Reduced bone mass and bone fragility –– Reduce molecular oxygen
–– Often seen in children with developmental –– Activate histamine during allergic
disorders and malabsorption reactions
–– Hypocalcemia – – Regulate serotonin degradation
–– Neuromuscular hyperexcitability, positive –– Oxidize ferrous iron
Chvostek and Trousseau signs, carpal-pedal –– Important for bone formation and collagen
spasm and connective tissue formation
• Food sources include as follows:
–– Chocolate and cocoa, crustaceans and
Chloride shellfish, lentils, nuts and seeds, organ
meats, and whole grains
• Chloride, along with sodium, maintains extra- • Deficiency is rare but can occur in special
cellular fluid volume, pH, and plasma conditions:
osmolality. –– Infants recovering from malnutrition with
• In addition, chloride in the form of hydro- chronic diarrhea fed cow milk
chloric acid is an important component of –– Patients on unsupplemented TPN
gastric juice. –– Young children fed on a milk-only diet
• Added salt (sodium chloride) is the main • Menkes kinky hair syndrome:
dietary source in the USA but is unnecessary –– X-linked recessive mutation in the ATP7A
to maintain health. gene.
• Good food sources include as follows: –– Gene codes for the copper-transporting
–– Dairy, celery, olives, seaweed, tomatoes: polypeptide that regulates copper levels.
21 Nutrition 733
–– Characterized by sparse, kinky hair, failure • Deficiencies of vitamin A, selenium, or iron

to thrive (FTT), developmental delays, sei- exacerbate effects of iodine deficiency.
zures, intellectual disability, and • Food sources include as follows:
hypotonia. –– Dairy, iodized salt, potatoes, seafood, sea-
–– Treatment with copper supplementation weed, meats, bread, and cereals
does not fully reverse the disease but is the –– Some foods contain goitrogens, substances
only available treatment. that interfere with thyroid hormone pro-
–– A milder form is called occipital horn syn- duction or utilization. They are not clini-
drome or cutis laxa. cally significant unless there is coexisting
• Wilson disease (Chap. 22 Gastroenterology): iodine deficiency.
–– Autosomal recessive disease (mutation in
the ATP7B gene).
–– Characterized by high levels of intracellu- I ron
lar copper.
–– Most significantly affected organs are the • Main functions are electron transfer and bind-
liver, heart, and nerves. ing of ligands.
–– Kayser-Fleischer rings are pathognomonic. • The major classes of iron-containing proteins
are as follows:
–– Heme proteins (hemoglobin, myoglobin,
Fluoride and cytochromes)
–– Iron sulfur enzymes (flavoproteins, heme
• Functions to prevent the initiation and pro- flavoproteins), iron storage
gression of dental caries—effect is topical. –– Transport proteins (transferrin, lactoferrin,
• Stimulates new bone formation. ferritin, and hemosiderin)
• Toxicity results in mottled teeth. • Functions:
• If water is fluoridated, recommended concen- –– Energy production
tration is 0.7–1.2 mg/L. –– Growth and development
–– Immune function
–– Red blood cell formation
Iodine –– Reproduction
–– Wound healing
• Essential component of thyroid hormones T3 • Deficiency:
and T4, which regulate protein synthesis and –– Long-term impaired mental and psycho-
enzymatic activity, especially in the develop- motor development
ing brain. –– Fatigue
• Congenital deficiency is called cretinism (see –– Pallor
Chap. 12 Endocrinology). –– Anemia
• Deficiency affects the muscle, heart, pituitary, –– Reduced capacity for play/work
and kidney: • Assess iron status with soluble transferrin
–– Decreased blood thyroid hormones receptor.
–– Hypothyroidism (see Chap. 12 • Ferritin is an acute-phase reactant and does
Endocrinology). not correlate with functional iron.
• Iodine deficiency is not as common because • Food sources include as follows:
of salt fortification with iodine. –– Meats, seafood, enriched/fortified breads
• Assess with serum thyroid hormone levels; and cereals, dark-green vegetables, beans
urine iodine. and peas
734 S. S. Baker
• Exclusively breastfed infants need iron sup- –– Regulation of the redox status of vitamin C
plementation at 4 months, as human milk has and other molecules, important for immune
insufficient iron to meet requirements. function and reproduction
• Increased needs for pregnant women and • Food sources include as follows:
young children. –– Eggs, whole grains, meats, nuts and seeds,
garlic, and seafood
• Only deficiency disease is Keshan disease; car-
Magnesium diomyopathy is seen in certain areas of China.
• Functions as a cofactor for more than 300

enzyme systems that generate energy both Sodium
aerobically and anaerobically for glycolysis
indirectly as part of the Mg-ATP complex or • Sodium, along with chloride, maintains
directly as an enzyme activator. extracellular fluid volume, pH, and plasma
• Required for mitochondrial oxidative osmolality. It maintains acid-base balance,
phosphorylation. blood pressure regulation, fluid balance,
• Food sources include as follows: muscle contraction, and nervous system
–– Leafy green vegetables, beans and peas, function.
dairy, whole grains, nuts and pumpkin seeds • Added salt (sodium chloride) is the main
• Deficiency can be manifested as hypocalce- dietary source in the USA but is unnecessary
mia, neuromuscular hyperexcitability, posi- to maintain health.
tive Chvostek and Trousseau sign, and • Good food sources include as follows:
carpal-pedal spasm. –– Dairy, especially cheeses, celery, olives,
seaweed, tomatoes, breads, meats
• May need additional salt in very hot climates,
Potassium during unaccustomed strenuous physical
activity, during diarrhea, if an ileostomy is
• Major intracellular cation required for normal present, especially in young children, and if
cell function. Important in acid-base balance. suffering from cystic fibrosis.
–– Bananas, beet greens, juices, dairy, oranges,
potatoes, prunes, spinach, tomatoes Zinc
• Severe deficiency is characterized by hypoka-
lemia and results in cardiac arrhythmias, • Functions as a component of enzymes in the
muscle weakness, hypercalciuria, and glu- maintenance of structural integrity of proteins
cose intolerance. and in the regulation of gene expression.
• Moderate deficiency occurs without hypoka- • Necessary for normal growth and develop-
lemia and is characterized by increased blood ment, immune function, nervous system
pressure and salt sensitivity, increased risk of function, protein formation, reproduction,
kidney stones, and increased bone turnover. taste, smell, and wound healing.
–– Meats, beans and peas, dairy, fortified cere-
Selenium als, seafood, whole grains, and nuts
• Zinc deficiency, first described in Iranian
• Functions as a selenoprotein, several of which male dwarfs, can occur with diarrhea caused
are oxidant defense enzymes: by infectious, inflammatory bowel disease,
–– Regulation of thyroid hormone action allergic gastroenteritis, etc.:
21 Nutrition 735
• Deficiency symptoms can be subtle and hard • Acrodermatitis enteropathica is a fatal auto-
to define: somal recessive disease if untreated that
–– Growth retardation affects the uptake of zinc through the bowel:
–– Alopecia –– Characterized by periorificial inflamma-
–– Diarrhea tion of tips of fingers and toes, hair loss,
–– Delayed sexual maturation and diarrhea.
–– Impotence –– It is treated with zinc supplementation.
–– Eye and skin lesions
–– Impaired appetite
• Supplement with 1 mg/kg/day as an oral solu- VITAMINS (TABLES 21.1
tion of zinc acetate (30 mg in 5 mL) if sus- AND 21.2)
pecting deficiency.
• Use serum zinc levels to assess as clinically • Vitamins are organic molecules that cannot
available, but serum zinc levels are not an be synthesized by the body and are required
accurate estimate of nutritional zinc status. in small amounts for normal function.
Table 21.1 Water-soluble vitamins

Vitamin Deficiency Toxicity Assess status
B1, Thiaminea Beriberi None known; water-soluble Red blood cell
Wet—high output cardiac failure vitamin and excreted in the urine transketolase level or
Dry—nervous tissue urinary thiamine level
Wernicke encephalopathy
Korsakoff syndrome
Infantile—affects infants of
malnourished mothers
B2, Riboflavin Very rare in the USA and usually None known; water-soluble Serum riboflavin level
associated with other deficiencies vitamin and excreted in the urine
If severe and prolonged, cataracts and
anemia
Vegans at risk of developing deficiency
B3, Niacin Pellagra—“3 Ds”: dermatitis (sun- Flushing, especially when used as Serum niacin level
exposed areas) , diarrhea, dementia a medication for lowering
cholesterol
B6 Microcytic anemia, dermatitis, cheilosis, None reported Serum level of pyridoxine
glossitis, depression, and confusion. Can 5′phosphate (PLP)
be associated with renal disease
Folic acid Associated with increased risk of neural Can mask neurological signs of Erythrocyte folate level
tube defects in infants from deficient B12 deficiency.
mothers. Supplement all women who can Perhaps accelerate progression of
become pregnant preneoplastic lesions
Vitamin B12 Megaloblastic anemia, fatigue, weakness, None reported Measure B12 level
constipation, weight loss, numbness and
tingling, depression, dementia,
confusion, soreness of mouth, difficulty
maintaining balance
Vitamin C Scurvy—inflammation and swelling of Low toxicity. Can see diarrhea, Serum level
gums, can lose teeth, petechiae, bleeding, nausea, and abdominal cramps
and malaise likely due to osmotic effect of
unabsorbed vitamin C supplements
B vitamins and folate deficiency rare in the USA, as grains are fortified
a
736 S. S. Baker
Table 21.2 Fat-soluble vitamins (summary)

Vitamin Deficiency Toxicity Assess status
A Earliest sign is night blindness; Pseudotumor cerebri, dizziness, Measure serum level
xerophthalmia is most common and is nausea, headaches, skin irritation,
often associated with Bitot spots. Top joint pain, coma, and death
cause of blindness in developing Provitamin A carotenoids are not
world. Increased severity and risk of associated with adverse effects
infections
D Rickets, failure of bone mineralization; Hypercalcemia leading to vascular Serum
osteomalacia in adults. Exclusively and tissue calcification, anorexia, 25-hydroxycholecalciferol
breastfed infants need to be weight loss, polyuria, arrhythmias levels
supplemented, as prolonged
breastfeeding without supplements is
associated with rickets
E May be seen in prematurely born Hemorrhage Serum level
infants and with fat malabsorption.
For those with abetalipoproteinemia
and AVED, very high doses are needed
K Bleeding. Important in newborns, None described Serum prothrombin, INR,
liver disease, anticoagulant therapy. Individual factors when
Perhaps osteoporosis indicated
AVED ataxia and selective vitamin E deficiency
• Vitamins can be supplied in food, as a supple- • Supplementation with biotin can reverse the
ment, and—in the case of vitamin D—from progression if congenital biotinidase defi-
ultraviolet (UV) light. ciency is recognized early.
• Toxicity is seen with the fat-soluble vitamins • Food sources include as follows:
A, D, and E. –– Eggs (cooked), meats, liver, salmon, fruits,
cruciferous vegetables, whole grains, and
The following are considered essential vitamins by avocados
the US Food and Drug Administration (FDA).
Folate/Folic Acid
Biotin
• Functions as a coenzyme in single-carbon
• Functions as a coenzyme in bicarbonate- transfers in the synthesis of DNA, purine syn-
dependent carboxylation for 4 enzymes, 3 of thesis, generation of folate, and amino acid
which are mitochondrial: interconversions.
• Deficiency: • Closely related to vitamin B12.
–– Dermatitis. • Deficiency:
–– Conjunctivitis. –– Low serum folate level
–– Alopecia. –– Megaloblastic anemia
–– Central nervous system abnormalities. –– Neutrophil hypersegmentation
–– Deficiency can be induced by consuming • Risk of neural tube defects (NTD) associated
raw egg white over long periods of time. with low folate in the periconception time. Any
–– Congenital deficiency occurs in the autoso- woman capable of becoming pregnant is at risk.
mal recessive metabolic disorder; biotini- • Food sources include as follows:
dase deficiency, in which biotin is not –– Enriched grains, beans and peas, green leafy
released from proteins in the diet (also see vegetables, avocado, asparagus, orange
Chap. 5 Metabolic Disorders).
21 Nutrition 737
iacin (Also Called Nicotinamide,

N –– Cheilosis, angular stomatitis, and angular
Nicotinic Acid) blepharitis.
–– Brown-Vialetto-Van Laere syndrome—
• Functions: rare neurological disorder caused by muta-
–– Biological redox reactions as nicotinamide tions of the SLC52A3 gene, which encodes
adenine dinucleotide (NAD) and NAD the intestinal riboflavin transporter and is
phosphate (NADP) associated with deafness, bulbar palsy, and
–– Cholesterol production respiratory difficulties. Riboflavin supple-
–– Conversion of food into energy ments can be life-saving.
–– Digestion and nervous system function • Food sources include as follows:
• Deficiency: –– Eggs, enriched grains, meats, dairy, seafood,
–– Pellagra, classic manifestation of severe green leafy vegetables, and mushrooms
deficiency characterized by dermatitis, a
hyperpigmented rash in sun-exposed areas
of skin, diarrhea, and dementia (“the 3 T hiamin (Also Sometimes Called
Ds”); rarely seen in the USA except in Vitamin B1 and Aneurin)
alcoholics, common in parts of Africa and
China • The first B vitamin identified.
• Food sources include as follows: • Functions as a coenzyme in the metabolism
–– Beans, meats, enriched grains and their of carbohydrates and branched-chain amino
products, nuts, seafood acids.
• Used to lower cholesterol. Side effect of high • Assess thiamine status with erythrocyte tran-
doses is flushing. sketolase activity, serum thiamine level, or
• Liver can synthesize 1 mg of niacin from thiamine in urine.
60 mg tryptophan provided there is adequate • Beriberi—rare in the USA:
riboflavin, B6, and iron. –– Wet beriberi:
◦◦ High-output cardiac failure
–– Dry beriberi (Wernicke-Korsakoff
Riboflavin (Also Sometimes Called syndrome):
Vitamin B2) ◦◦ Polyneuritis, ataxia, altered mental sta-
tus, nystagmus, and confabulation; gen-
• Riboflavin is bright yellow and gives urine a erally seen in alcoholics in the USA
bright-orange color if consumed in quantity. –– Acute infantile beriberi occurs in infants of
• Functions: thiamine-deficient mothers who are exclu-
–– Fat metabolism sively breastfed:
–– Hormone production ◦◦ Hypotension, tachycardia, lactic acido-
–– Nervous system function sis, and a high infant mortality (Shoshin
• Deficiency often occurs in conjunction with beriberi).
other B vitamin deficiencies: ◦ ◦ Intravenous thiamine reverses the dis-
–– Sore throat. ease and is diagnostic; rare in the USA
–– Glossitis. and seen in India when breastfeeding
–– Conjunctivitis. mother’s diet is highly restricted.
–– Seborrheic dermatitis. • Food sources include as follows:
–– Normochromic, normocytic anemia. –– Beans and peas, enriched grains, unpol-
ished rice, meats, nuts, sunflower seeds
738 S. S. Baker
itamin B6 (Pyridoxine and Related

V ileum; rare in children. Treatment is with B12
Compounds) injections. Some use high-dose oral or nasal
spray.
• Functions as a coenzyme in the metabolism • Food sources include as follows:
of the following: –– Dairy, eggs, fortified grains and cereals,
–– Amino acids—protein metabolism meats, seafood
–– Glycogen—carbohydrate metabolism • Supplement those consuming a vegan diet.
–– Sphingoid bases—fat metabolism
• Deficiency is rare and if present usually
occurs with other B vitamin deficiencies: Vitamin A
–– Seborrheic dermatitis
• Fat-soluble retinoids including retinol, retinal
–– Microcytic anemia
and retinyl esters, carotenes, and
–– Epileptiform convulsions
beta-carotenes.
–– Depression
• Functions:
–– Confusion
–– Vision
–– Integrity of epithelial and mucous tissue
–– Chickpeas, noncitric fruits, fish, and
–– Growth and development
potatoes
–– Reproduction
–– Immune regulation
Vitamin B12 (Also Called Biologically • Supplementation with vitamin A reduces
mortality in measles, acute pneumonia, and
Active Cobalamins)
infantile diarrhea in vitamin- insufficient
• Functions as a cofactor for 2 enzymes, populations.
methionine synthase (transfers a methyl • Deficiency characterized by as follows:
group from methyltetrahydrofolate to –– Progressive loss of vision.
homocysteine) and L-methylmalonyl-CoA –– Night blindness is one of first signs of
mutase (converts L-methylmalonyl-CoA to deficiency.
succinyl-CoA). –– Xerophthalmia (dry eyes).
• Metabolically closely related to folate. –– Keratomalacia—ulceration of the cornea.
• Deficiency manifested as follows: –– Bitot spots, buildup of keratin in the con-
–– Megaloblastic anemia junctiva, on either or both sides of the
–– Neutrophil hypersegmentation pupil, are pathognomonic of vitamin A
–– Tingling and numbness in extremities, deficiency.
worse in the lower limbs • Best food sources are as follows:
–– Vibratory, position sense, and motor –– Liver, cod liver oil often used to treat defi-
disturbances ciency in the developing world
–– Cognitive problems from memory loss to • Hypervitaminosis:
frank dementia –– Pseudotumor cerebri.
• Neurological disturbances occur at later –– Hypercalcemia.
stages of deficiency; rare in children. –– Hepatitis.
• Pernicious anemia is the end stage of an auto- –– Poor weight gain.
immune disorder in which parietal cell auto- –– Bone pain/swelling among other
antibodies prevent the synthesis of intrinsic symptoms.
factor, necessary for B12 absorption in the – – Treatment is to stop intake of vitamin A.
21 Nutrition 739
• Carotenoids found in yellow vegetables do –– Available in fortified dairy, eggs, some

not cause hypervitaminosis A but can cause beverages, liver from any mammal, and
yellowing of the skin. supplements
• All breastfed infants should be supplemented
with vitamin D, 400 IU, starting at birth and
itamin C (Refers to Ascorbic
V continuing until they consume 1 quart of for-
and Dehydroascorbic Acid) mula daily.
• Vitamin D insufficiency/deficiency is often
• Water-soluble vitamin. seen in children and should be corrected:
• Functions as an antioxidant by providing –– Deficiency = serum level of 25-hydroxyvi-
reducing equivalents for biochemical reac- tamin D < 20 ng/mL
tions, often for reactions requiring a reduced –– Insufficiency = serum level of
iron or copper metalloenzyme; needed for the 25-hydroxyvitamin D 20–29 ng/mL
synthesis of collagen, L-carnitine, proteins, –– Sufficiency = 30–100 ng/mL
and some neurotransmitters. • Correct vitamin D deficiency or insufficiency
• Deficiency: with 2000 IU PO daily or 50,000 IU PO
–– Scurvy (abnormal collagen) characterized weekly for 6 weeks.
by the following: • Hypervitaminosis D is characterized by the
◦◦ Weakness, tiredness following:
◦◦ Brown skin spots –– Vomiting
◦◦ Decreased red blood cells –– Decreased appetite
◦◦ Gingival disease –– Irritability
◦◦ Bleeding from mucous membranes –– Constipation
◦◦ Changes to hair –– Metastatic calcification of soft tissue
◦◦ Poor wound healing
–– Citrus fruits, tomatoes and their juice, pep- Vitamin E
pers, broccoli
• A fat-soluble vitamin that includes
α-tocopherol, β-tocopherol, γ-tocopherol,
Vitamin D (Fat-Soluble Vitamin, Also and δ-tocopherol.
Called Calciferol) • Likely functions as an antioxidant that prevents
propagation of lipid peroxidation, but unlike
• Functions to maintain normal serum calcium other vitamins, a specific purpose in a required
and phosphorus levels. metabolic function has not been defined.
• Deficiency: • Deficiency is rare, but has been associated
–– Rickets, inadequate skeletal mineraliza- with the following:
tion, characterized by widening of the end –– Spinocerebellar ataxia
of long bones, rachitic rosary (rib beading), –– Myopathies
bowing of the legs, craniotabes, and—in –– Dysarthria
adults—osteomalacia –– Absence of deep tendon reflexes
• UV light is important in the synthesis of vita- –– Loss of vibratory sense
min D in the skin. Sunlight, however, is a risk –– Hemolytic anemia
of skin cancer. –– Retinopathy
• Naturally present in few foods: –– Impaired immune response
740 S. S. Baker
• Deficiency has been described in prematurely MACRONUTRIENTS

born infants. Treatment is vitamin E
supplementation. Macronutrients are considered a type of food (e.g.,
• Patients with abetalipoproteinemia require fat, protein, carbohydrate) required in large
high doses to prevent poor nerve tissue func- amounts in the human diet:
tion, muscle weakness, and retinal degenera-
tion leading to blindness.
Energy
• Ataxia with isolated vitamin E deficiency
(AVED), caused by a mutation in the TTPA • Calories or energy required to sustain the
gene, is a rare congenital disorder that requires body’s functions including respiration, circu-
high doses to prevent nerve damage and lation, physical work, and maintenance of
inability to walk. core body temperature; available from foods
• Food sources include as follows: and released by oxidation yielding chemical
–– Fortified cereals and juices, green leafy energy.
vegetables, nuts and seeds, vegetable oils, • Estimation of caloric requirement has become
peanuts complicated, as there is now a recommendation
to include activity in the estimation and there
is no RDA for energy.
Vitamin K
• Estimates that can be used clinically (not RDA):
• A fat-soluble vitamin that includes phylloqui- –– Preterm infants: 90–120 kcal/kg/day;
nones and menaquinones. important to follow growth
• Functions as a coenzyme during the synthesis –– Infants: 100 kcal/kg/day
of the biologically active form of proteins –– Children 1–8 years: about 85 kcal/kg/day
involved in blood coagulation and bone –– Children 9–13 years:
metabolism: ◦◦ Boys 50 kcal/kg/day
–– Plasma prothrombin (coagulation factor II) ◦◦ Girls 40 kcal/kg/day
–– Plasma procoagulants (factors VII, IX, and –– Children 14–18 years:
X) ◦◦ Boys 37 kcal/kg/day
–– Likely inhibits arterial calcification ◦◦ Girls 30 kcal/kg/day
• Deficiency is characterized by vitamin K-
responsive hypoprothrombinemia, prolonged
at
F
PT, INR, and bleeding:
–– Vitamin K is poorly transported across the • Fats are essential nutrients that are a fuel
placenta, so newborn infants are at risk of source and aid in the absorption of fat-soluble
deficiency and should be treated with a vitamins and carotenoids.
single dose of 0.5–1.0 mg IM vitamin K at • They function in cell signaling and alter
birth. expression of specific genes.
–– Deficiency occurs in cholestatic liver dis- • There is no recommended dietary intake
ease and may cause bleeding in this because there are insufficient data.
circumstance. • 98% of dietary fat is triacylglycerol:
• Food sources are as follows: –– Essential fatty acids:
–– Mostly green vegetables—vitamin K is an ◦◦ Linoleic (n-6):
electron acceptor in photosynthesis ▪▪ Thought to be “pro-inflammatory.”
21 Nutrition 741
▪▪ Deficiency is dermatitis. –– Monosaccharides are 1 sugar, e.g.,

▪▪ Food source is fatty fish. glucose.
◦◦ Linolenic acid (n-3): –– Disaccharides are 2 sugars linked together,
▪▪ Thought to be “anti-inflammatory.” e.g., lactose.
▪▪ Deficiency is dermatitis. –– Oligosaccharides are 3 to 10 sugars linked
▪▪ Food source is fatty fish. together, e.g., raffinose and stachyose.
◦◦ Trans-fatty acids: –– Polysaccharides contain more than 10 sug-
▪▪ Not essential and provide no known ars linked, e.g., starch or glycogen.
benefit for human health; should not –– Added sugar are sugars and syrups added
be eaten to foods during processing or preparation:
• Recommendations for fat intake: ◦◦ Baked goods like cookies, cakes, pies
–– 2 to 3 years of age: total fat 30–35% of ◦◦ Beverages like fruit drinks, sodas
calories. ◦◦ Dairy like yogurt with fruit syrup
–– 4 to 18 years of age: total fat 25–35% of ◦◦ Candy
calories. –– Examples of types of added sugar:
–– Most fats should come from polyunsatu- ◦◦ White sugar
rated and monounsaturated fatty acids ◦◦ Brown sugar
(fish, nuts, vegetable oils). ◦◦ Raw sugar
◦◦ Corn syrup and corn syrup solids
◦◦ High-fructose corn syrup
Protein ◦◦ Malt syrup
◦◦ Maple syrup
• Protein is the major functional and structural
component of the body:
–– Consists of amino acid chains BREASTFEEDING (TABLE 21.3)
–– Complex physical structure
–– Considered as indispensable (body cannot • Breastfeeding is recommended as the pre-
make), dispensable (body can make), or ferred feeding for all infants.
conditionally indispensable (body cannot • Human milk is dynamic; nutrient concentra-
make sometimes or has increased require- tions vary overtime (months and within a sin-
ment in certain circumstances—e.g., argi- gle day, within a single feed, and among
nine, glycine, tyrosine) women).
–– Requirements based on age: • No cow’s milk before 1 year of age because
◦◦ Birth to 6 months—human milk, esti- of GI blood loss. Use infant formula if need-
mated at about 1.5 g/kg/day, is highly ing supplementation.
variable.
◦◦ 7–12 months: 1.2 g/kg/day.
◦◦ 1–3 years: 1.05 g/kg/day. olostrum
C
◦◦ 4–13 years: 0.95 g/kg/day.
◦◦ 14–18 years: 0.85 g/kg/day. • Colostrum secreted for the first 7 days after
birth; volume varies from 2 to 20 mL per
feeding.
Carbohydrates • Consists of mammary duct contents, immu-
nologically active cells.
• Carbohydrates provide energy, especially for • Yellow color caused by carotenoids.
the brain: • High levels of vitamin E and protein.
742 S. S. Baker
Table 21.3 Difference between colostrum and mature and other macromolecules so they cannot
breast milka bind to intestinal cells; inhibits pro-
Mature breast inflammatory responses to oral agents.
Constituent (per liter) Colostrum milk –– Provides protection against enteric and
Appearance Creamy, Thin, white
other diseases in naturally immunized
yellow
Volume (mL/24 hour)b ~100 750–1050 mothers.
Energy (Kcal) 571 ± 80 650–700
Total protein (g) 14–65 9–13
Nitrogen (g)—food 3.0 1.9 Transition Milk
protein 3.8 3.5
Casein (g) 11–15 5–6 • Gradual change from colostrum to mature
Whey (g) 2.0 0.5–1.0
IgA (g) 0.12 0.2 milk.
IgM (g) 3.5 1–3 • Protein, immunoglobulin, and fat-soluble
Lactoferrin (g) 0.1–0.2 0.1 vitamin content decreases; lactose, water-sol-
Lysozyme (g) uble vitamins, fat, and total caloric content
Total carbohydrate (g) 26–76 50–83
increases.
Lactose (g) 20–30 67–70
Oligosaccharides (g) 22–24 5–15 • 90% of women whose milk contained 20 g or
Glucose (g) 0.2–1.0 0.2–0.3 more of fat/feeding on the seventh day of lac-
Total fat (g) 10–27 28–49 tation successfully breastfed for at least
Triglycerides (g) 14.5–19.5 34–47 3 months. 80% of women with 5–10 g fat/
Fatty acids (g) 13–17 30–42
feeding are not breastfeeding at 3 months.
Cholesterol (g) 0.2–0.3 0.1–0.2
Vitamins 5.35 1.8–3.0
Total carotenoids 1510 750
(umol) 19 140 Mature Breast Milk
A (ug) 300 400
B1 (ug) – 120–150 • Transition milk produced from about 7 to
B2 (ug) – 0.5–1.0
10 days after birth:
B6 (ug) 750 1600
B12 (ug) 1830 2460 –– Gradual change from colostrum to mature
Nicotinic acid (ug) 0.6 6 milk.
Pantothenic acid (ug) 0.5 1.4 –– Protein, immunoglobulin, and fat-soluble
Biotin (ug) 0.1–0.3 0.33 vitamin content decreases; lactose, water-
Folic acid (ug) 15 2.5
soluble vitamins, fat, and total caloric con-
D (ug) 59 50
E (ug) 2–5 2–3 tent increases.
C (ug) • Mature milk produced 7–10 days after birth
K (ug) recommended as exclusive food for infants
a
Human milk is highly variable in content from woman to until 4–6 months:
woman, day to day, fore- vs. hind milk –– Reliable source of all nutrients for healthy
b
Volume is highly variable
term infants except the following while
exclusively breastfeeding for the first
• Low fat content.
4–6 months:
• Contains immunoglobulins, especially immu-
◦◦ Vitamin D—supplement with 400 IU daily.
nologically active secretory IgA, which
◦◦ Iron—supplement with 1 mg elemental
decrease overtime:
iron/kg/day, starting at 4 months.
–– IgA offers protection of the intestinal epi-
◦◦ B12 for babies of vegan mothers.
thelial barrier by binding bacteria, toxins,
21 Nutrition 743
–– Contains protective factors in addition to • Chemical contamination:

immunoglobulins, including as follows: –– Many women have detectable levels of
◦◦ Oligosaccharides chemical agents in breast milk.
◦◦ Lactoferrin –– The CDC recommends continued breast-
◦◦ Lactoperoxidase feeding despite the presence of chemical
◦◦ Lysozyme toxins in milk.
◦◦ Soluble CD14 • Impediments to breastfeeding:
◦◦ Defensins –– Work
◦◦ Live cells: activated neutrophils, macro- –– Public attitudes
phages, and lymphocytes –– Lack of family/peer support
◦◦ Cytokines –– Lack of access to clean rooms to express
◦◦ Opsonins while at work
–– Contains growth factors: –– Stress
◦◦ Epidermal growth factor –– Mastitis
◦◦ Factors that affect neonatal intestinal –– Lack of understanding that first week of
development nursing can be painful to nipples, a condi-
◦◦ Erythropoietin tion that passes
◦◦ Insulin • Normal feeding pattern in breastfeeding:
◦◦ Insulin-like growth factors I and II –– Feeding is dependent on infant cues pro-
◦◦ Lactoferrin gressing from hands moving toward the
◦◦ Nerve growth factor mouth, sucking on fists and fingers, fussi-
◦◦ Transforming growth factor-α ness, agitation, flailing of extremities, and
• Contraindications to breastfeeding: finally loud, persistent crying. The sequence
–– Women infected with HIV or T-cell lym- can last 45 min, including nuzzling.
photropic virus in the developed world –– In the first 1–2 weeks, infants are fed 8–12
–– Active pulmonary tuberculosis and not times in 24 h.
completed 2 weeks of treatment –– From about 2–4 weeks, frequency is about
–– Infants with inborn errors of metabolism, 7 to 9 times in 24 h.
such as galactosemia –– Both breasts are offered at each feeding.
• Medications and breastfeeding: –– Time to complete a feed varies with
–– Many are safe (up-to-date information: US mother-infant dyad from about 10–15 min.
National Library of Medicine, Drugs and • Stools vary overtime:
Lactation Database (LactMed), https:// –– Meconium is cleared within 3–4 days of life.
toxnet.nlm.nih.gov/newtoxnet/lactmed. –– After day 4, most infants have 3 or more
htm). stools a day
• Contraindicated medications during –– Some breastfed infants may stool infre-
breastfeeding: quently—once every 7–10 days. As long as
–– Antithyroid medications healthy and growing, it is not a concern.
–– Radioactive drugs –– Stools are pale yellow after about the fifth
–– Most chemotherapy drugs day of life, but can be green and frothy.
–– Metronidazole • Colitis (blood in stools)—most likely cause
–– Diazepam in healthy child is protein intolerance:
–– Sulfonamides –– Can stop breastfeeding and use a hydro-
–– Tetracycline lyzed infant formula
744 S. S. Baker
–– Preferable to continue breastfeeding and Table 21.4 Difference between breast milk and formula
remove dairy products from mother’s diet; Mature
supplement her with calcium. Constituent/L human milka Formula
Energy (kcal) 650–700 680
Total protein (g) 8–21 14
Casein:whey 3:7 Variable
FORMULA FEEDING (approximate)
(TABLE 21.4) Fat (g) 28–49 36
Carbohydrates + + or lactose
Formula Feeding for Term Infants Lactose free available
Vitamins Inadequate Adequate
• No cow’s milk before 1 year of age, associ- Vitamin D
ated with GI blood loss. Minerals Inadequate Adequate
• Feed formula only until 1 year of age. Iron Inadequate Adequate
• Formula types are grouped according to pro- Zinc
tein, fat, or carbohydrate content. DHA/ARA ✓ ✓
Oligosaccharides ✓
Enzymes ✓
Protein Amylase ✓
• Cow milk based: Lipase ✓
–– Standard iron-fortified formula of choice Protease ✓
when not breastfeeding or breastfeeding Antiproteases ✓
stopped before 1 year. Arylsulfatase ✓
Catalase ✓
–– No vitamin or mineral supplementation is Lysozyme ✓
necessary. Histaminase ✓
• Soy protein based: Peroxidases ✓
–– Support growth and development equiva- Ribonuclease ✓
lent to that of breast milk or cow milk- Platelet activating acetyl ✓
hydrolase factor ✓
based formula. Growth factors/hormones ✓
–– Recommended for galactosemia, heredi- Erythropoietin ✓
tary lactose intolerance, documented IgE- Insulin ✓
associated cow milk allergy, parents who Insulin-like growth ✓
want a vegetarian diet for children. factors I and II ✓
Lactoferrin ✓
–– Not recommended for the following: Nerve growth factor ✓
◦◦ Preterm infants with birth weights Relaxin ✓
< 1800 g Transforming growth ✓
◦◦ Infants with cow milk protein-induced factor α
enterocolitis or enteropathy Anti-infective/ ✓
immunological ✓
◦◦ Prevention of colic Opsonins ✓
◦◦ Prevention of allergy Enzymes ✓
◦◦ Infants who have sucrose-isomaltose Immunoglobulins ✓
deficiency Cytokines ✓
Live cells ✓
• Hydrolyzed cow milk:
–– Developed for infants who cannot digest or
a
Human milk is highly variable in volume and content from
woman to woman, day to day and fore- vs. hind milk. There
are intolerant of intact cow milk protein. are a plethora of infant formulas that are constantly being
–– Protein is first heat treated and then enzy designed, changed, and marketed. This table provides infor-
matically treated to give peptide chains. mation on a “typical” term infant formula.
21 Nutrition 745
–– Lactose free; contains sucrose, tapioca sometimes fish oils; lecithin- emulsifying
starch, corn syrup solids, cornstarch as agent.
carbohydrates. • Rarely contain lipids from dairy source in
–– Contains varying amounts of medium- USA.
chain triglycerides (MCTs), polyunsatu-
rated vegetable oil to supply essential fatty Stooling Pattern in Formula-Fed Infants
acids • Meconium passes by 3–4 days.
–– Indications: • Stooling is about once a day after meconium
◦◦ Cow milk protein-induced enterocolitis passage.
◦◦ Malabsorption due to GI or hepatobili- • Hydrolyzed formula-fed infants can stool up
ary diseases such as cystic fibrosis, short to 12 times a day.
gut, biliary atresia, cholestasis, or pro-
longed diarrhea Colitis in Formula-Fed Infants or Blood in Stool
• Chemically defined: • Most likely cause is milk protein
–– Single amino acids are formulated specifi- intolerance.
cally for infants with extreme protein • Change formula to hydrolyzed protein and
hypersensitivity whose symptoms persist reassess. If blood in stools resolves, continue
on hydrolyzed formulas. hydrolyzed formula for the first year.
• In the unlikely event blood in stool does not
Carbohydrate resolve, use a chemically defined formula;
• Lactose, major carbohydrate in human milk reassess. If blood resolves, continue chemi-
and in most cow milk formula: cally defined formula for the first year.
–– Lactose is a disaccharide hydrolyzed in the • If blood does not resolve, refer to GI to assess
small intestine to produce galactose and for very early-onset inflammatory bowel dis-
glucose. ease (VEO-IBD)
–– Some reaches the colon where it is fer- • For term infants who are failing to thrive on
mented, producing acid that helps to main- infant formulas, after establishing there is no
tain an environment that fosters acidophilic medical reason, formula can be concentrated
bacteria that suppress the growth of patho- to 26 kcal/oz. by increments of 2 kcal/oz.
genic organisms. over the usual 20 kcal/oz.
–– Soy, hydrolyzed protein, and chemically
defined formulas do not contain lactose.
–– Other carbohydrates included in some INTRODUCTION OF SOLIDS
formulas:
◦◦ Prebiotics—diverse group of complex • Exclusive breastfeeding recommended for
nondigested carbohydrates fermented about 4–6 months. After addition of solids
by gut bacteria and thought to promote (complementary foods), breastfeeding should
growth of advantageous bacteria continue for as long as the mother and infant
◦◦ Some examples: oligosaccharides, fruc- wish.
tooligosaccharides, inulin • For breastfed infants, complementary foods
are introduced at 4–6 months because human
Fat milk becomes limiting in calories, iron, and
• Formulas can include medium-chain triglyc- zinc.
erides (6–12-carbon length), long-chain tri- • Thus, it is best to start with meats or iron-for-
glycerides, vegetable oil blends, egg, and tified cereals.
746 S. S. Baker
• For formula-fed infants, introduce comple- • Toddlers require about 3 meals and 2 to 3
mentary foods at 4–6 months. snacks a day:
• Delaying the introduction of solid foods –– Diet in transition.
beyond 4–6 months of age may increase the –– About 1000–1400 kcal/day.
risk of allergy. –– Whole (full fat—3% fat) milk until age
• The texture of complementary foods should 2 years; then change to low-fat or fat-free
be advanced based on the oral motor skills of milk.
the infant. • At risk of iron deficiency, especially if breast-
• Introduce only one new food at a time every fed and not supplemented with iron in the
3–5 days. first year of life.
• No salt or sugar to be added to the infant’s • Frequently exhibit food “neophobia”—reluc-
diet. tance to try new foods; offer new foods at
• Delay introduction of cow milk or other ani- least 10 times.
mal milks until 12 months of age to prevent • May exhibit “food jags”—will only eat a cer-
GI blood loss. tain food or limited variety of foods for a
period of time; generally passes with time.
Home-Prepared Baby Foods (www.foodsafety. • Caution parents about small, hard foods, as
gov) they present a choking hazard.
• Foods can safely be prepared from whole • Many prepared foods for toddlers are high in
foods with the following precautions: salt and added sugars—help parents read
–– Best to begin with fresh foods. If using labels and make good choices.
processed fruits and vegetables, use prod-
ucts without added sugar or salt. Children
–– No unpasteurized dairy products. • Develop healthy behaviors around eating.
–– No honey. • Avoid food fights—parents never win.
–– No juice in the first year. • Avoid foods with added sugars and salt for
–– Wash hands and equipment. meals and snacks.
–– Use separate cutting boards for meat, poul- • Calories depend on size and activity level, in
try, and fish, i.e., do not cut fresh vegeta- general about 1200–1400 kcal/day.
bles on a cutting board used for meats/fish. • Provide fresh fruits and vegetables; if canned
–– Wash fruits and vegetables, even if they or frozen, choose those without added sugar
will be peeled. and salt.
–– Cook meats, poultry, and fish well—meat • Make half of the meal plate fruits and/or
to internal temperature of 160°, fish to at vegetables.
least 145°, white meat poultry to 165°. • Lean meat, nuts, eggs as protein source.
–– OK to freeze for about 1 month. • Serve whole-grain breads and cereals.
• Reduce refined grains in the diet.
Toddlers • Avoid frying: broil, grill, or steam.
• Generally defined as children from 12 to • Limit fast food and junk food.
36 months of age. • Offer water or milk instead of sugary fruit
• Most studies show a consistency of toddler drinks and sodas.
intake supporting the observation that if they
are presented with a good-quality diet, they Adolescents
will self-regulate their intake. • Healthy diet:
• Snacking is important—about 24% of con- –– Includes the following:
sumed calories.
21 Nutrition 747
◦◦ A variety of vegetables from all sub- –– Use 12.5% solution to avoid venous
groups—dark green, red, orange, irritation.
legumes, starch • Fat:
◦◦ Whole fruits –– Plan for lipid to provide 25–40% of
◦◦ At least half of grains as whole grains calories.
◦◦ Fat-free or low-fat dairy products –– Use 20% fat emulsion.
◦◦ Protein from seafood, lean meats, eggs, –– Infants require a minimum of 0.5 g/kg/day
beans and peas, nuts, seeds, soy fat to protect against essential fatty acid
products deficiency.
◦◦ Oils • Minerals:
◦◦ Less than 10% of calories from saturated –– Metabolic bone disease is common.
fats –– Calcium to phosphorus ratio 2:1 for opti-
◦◦ Less than 2300 mg sodium mal utilization.
◦◦ Less than 10% of calories from added –– Lower pH of TPN solution, more soluble
sugars calcium and phosphorus:
◦◦ No, or as little as possible, trans-fats ◦◦ Can add cysteine to lower pH and permit
–– Caloric requirement depends on size and more calcium and phosphorus to solubi-
activity and especially high for those lize—talk with pharmacist.
engaging in aerobic sports (1500– ◦◦ If using TPN for 2 weeks or less, the
3000 kcal/day). only trace element needed is zinc.
–– Girls at risk of iron deficiency. • Vitamins—use commercially available pre-
• Exercise. term vitamin mixture.
• Sleep 7–9 hours a night.
Complications of TPN
• Growth failure caused by inadequate calories
PREMATURE INFANTS or an imbalance of nutrients.
• Hyperglycemia—check rate of glucose
• No DRI or RDA for premature infants, but administration; reduce rate of administration;
consensus recommendations exist that depend consider insulin.
on weight and whether enteral or parenteral • Hyperlipidemia—triglycerides to 250–300 mg/
feeding is prescribed. dl are acceptable. Reduce lipid infusion.
• Goal is to mimic fetal growth rate, but rarely • Sepsis caused by line contamination—careful
achieved in the neonatal ICU. handling of the line.
• Liver toxicity—reduce reliance on TPN as
Parenteral Nutrition (Total Parenteral Nutrition much as possible; if possible, some enteral
or TPN) feeds.
• Fluid: • Consider intravenous fat blends designed for
–– > 1000 g birth weight—60–80 mL/kg/day infants such as Omegaven or Smoflipid.
for the first day; then increase by 20 mL/ • Aluminum toxicity—reduce TPN as much as
kg/day to a maximum of 120–140 mL/kg/ possible, as this is a contaminant that is diffi-
day. cult to avoid.
–– < 1000 birth weight—higher rates.
• Proteins: Enteral Feeding
–– Provide minimum of 2–3 g/kg/day amino • Human milk is enteral feeding of choice for
acids. premature infants but is nutritionally
• Glucose: inadequate.
748 S. S. Baker
• Use human milk fortifiers that provide addi- NUTRITION SUPPORT

tional protein, minerals, and vitamins.
• Human milk is associated with decreased Necessary when children cannot or will not con-
enterocolitis and perhaps improved neurolog- sume adequate nutrients to support normal growth
ical development. and development and to replete malnourished
states. Nutrition support can be supplements, tube
Premature Formula feedings, or intravenous.
• Use commercially prepared preterm infant
formulas that are designed to meet the needs Start with Careful Nutrition Assessment and
of the preterm infant and usually contain as Repeat as Indicated, Usually Weekly Initially
follows: • Diet history
–– Energy: Requirement is estimated at • Anthropometrics:
90–120 kcal/kg/day; follow growth; weight –– Weight
gain should be about 15 g/kg/day. –– Height
–– Protein: Provide minimum of 3–4 g/kg/day –– Body mass index (BMI)
amino acids. Soy-based are formulas not –– Mid-arm circumference (estimate of lean
recommended. body mass)
–– Carbohydrate: Content of most preterm –– Triceps skinfold (estimate of fat mass)
formulas provides 10–14 g/kg/day or • Laboratory:
40–50% of calories. –– Complete blood count (CBC)
–– Fat: Formulas for premature infants have a –– Electrolytes
fat blend: –– Minerals, especially phosphorus and
◦◦ Medium-chain triglycerides (MCTs) magnesium
◦◦ Vegetable oils rich in polyunsaturated –– Proteins, albumin
long-chain triglycerides –– Vitamins
◦◦ Meets essential fatty acid requirement of –– Dual-energy X-ray absorptiometry (DXA)
at least 3% of energy as linoleic acid for bone mineral status
–– Minerals—preterm infants have increased
needs:
Supplements
◦◦ Metabolic bone disease is common.
• Use if child is willing to consume a
◦◦ Goal for calcium: 60–80 mg/kg/day.
supplement.
◦◦ Goal for phosphorus: 39–67 mg/kg/day.
• Many available over the counter and/or with a
• Mix as 22 or 24 kcal/oz.
prescription.
• Higher vitamins and then regular formulas,
• Some examples:
supplementation not generally required.
–– PediaSure
–– Ensure
After Discharge of a Preterm Infant • Prescribe a medical food (FDA oversight).
• Close follow-up to assure adequate growth. Medical foods are specially formulated and
• Discharge can be at 1500 g. intended for the dietary management of a
• Very-low-birth weight infants at risk of sig- disease that has distinctive nutritional needs
nificant nutritional deficits. that cannot be met by normal diet alone:
• Human milk preferred. –– Used to treat inborn errors of
• Requires supplementation with a fortifier for metabolism
a minimum of 12 weeks.
21 Nutrition 749
–– Used as supplements for some diseases P arenteral Nutrition (PN)

associated with malnutrition, such as
inflammatory bowel disease • Indications:
–– Used in malabsorption, allergy –– If the GI tract is partially functional, use
enteral feeds in addition to PN.
–– Use only when not possible to meet nutri-
Enteral Tube Feeds tional requirements via the GI tract.
–– Use when the GI tract is dysfunctional and
• Nasogastric (NG) tube feeding: anticipate prolonged course.
–– Indications: –– Must be hemodynamically stable.
◦◦ Cannot or will not consume adequate –– Correct all electrolyte and mineral abnor-
nutrition to support normal growth and malities before starting PN.
development and reverse malnutrition if –– PN cannot be used to correct electrolyte
present and mineral abnormalities.
◦◦ Short-term support and/or rehabilitation –– Do not use for short-term nutrition
–– Complications: support:
◦◦ Misplaced tube (into lung), perforate ◦◦ Premature infants (see section on pre-
esophagus mature infants)
◦◦ Aspiration ◦◦ 1–3 days infants
◦◦ Delivery of inadequate nutrients (under- ◦◦ 4–5 days children and adolescents
estimate needs) ◦◦ 7–10 days young adults
◦◦ Delivery of excessive nutrients (overes- • Complications:
timate needs) –– Inherently nonphysiologic:
• Percutaneous endoscopic gastrostomy ◦◦ Nutrients delivered directly into the sys-
(PEG) tube feeding: temic circulation
–– Indications: ◦◦ Bypasses modulating effect of the GI
◦◦ Long-term nutrition support tract and liver
◦◦ Placement, endoscopic or laparoscopic –– Abnormal or imbalance in supplied
–– Complications: nutrients
◦◦ Tethered colon –– Line sepsis
◦◦ Bleeding –– Line occlusion
◦◦ Infection –– Hyper-/hypoglycemia
◦◦ Buried bumper –– Hyperlipidemia
◦◦ Delivery of inadequate nutrients (under- –– Prescription to fluctuate with disease state,
estimate needs) interventions, etc.
◦◦ Delivery of excessive nutrients (overes- • Peripheral:
timate needs) –– Solution 900 mOsm/L or less.
• Bolus vs. continuous feeds: –– Need frequent replacement.
–– When possible, bolus feeds are preferred: –– Use for days or weeks only.
◦◦ Normal cycling of fed and unfed state –– Use in conjunction with enteral feeds.
◦◦ Allows for cycling of hunger and satiety –– Easy insertion.
hormone cholecystokinin • Central:
◦◦ Easier for family to provide –– Several choices for lines:
–– Continuous feeds: ◦◦ Tunneled cuffed catheter:
◦◦ Cannot tolerate bolus feeds ▪▪ Placed surgically
750 S. S. Baker
▪▪ Lower infection rate –– Decreased activity, apathetic

▪▪ Appropriate for long-term PN –– Delayed motor and mental development
◦◦ Peripherally inserted central catheter • Underweight, low weight for height, wasting
(PICC): –– Indicates recent and severe weight loss,
▪▪ Appropriate for support for several may be associated with an infection
months –– Increase in total body water as fat mass is
▪▪ Easily placed lost
▪▪ Careful to estimate insertion length • Kwashiorkor (edematous malnutrition):
accurately –– Appearance:
▪▪ Confirm position radiographically –– Irritable
◦◦ Implanted ports: –– Subcutaneous tissue present
▪▪ Long-term PN –– Dermatosis—hyperpigmentation with
▪▪ Surgically placed peeling skin
▪▪ Accessed via a needle into the port –– Hypopigmented hair
• Prescription of nutrients—based on nutri- –– Hepatomegaly caused by fat deposition
tional assessment above, specific disease, and (fatty liver)
the DRI for age: –– Edema
–– Get help from a dietitian and pharmacist. –– Hypoproteinemia
–– Most hospitals have standard formulas that –– Hypotension, bradycardia, thermolabile
can be used. –– Susceptible to infection
–– Determine energy requirement. –– Intravascular volume depletion (in spite of
–– Determine protein needs. peripheral edema)
–– Determine fat. –– Deficiency in protein
–– Provide electrolytes, minerals, trace ele- –– Hypoglycemia
ments, and vitamins. • Marasmus (wasting malnutrition):
–– Appearance:
–– “Wizened old man”
NUTRITIONAL DISORDERS –– Emaciated and weak appearance
–– Irritable
Protein energy malnutrition (PEM) is a deficiency –– Thin, dry skin
or imbalance in intake of energy and/or –– Severe loss of subcutaneous tissue
nutrients—common. –– Thin, sparse hair
–– Deficiency in calories and energy
primarily
Undernutrition –– Adaptive to food restriction
–– Severe wasting of all tissues
In addition to protein energy deficits, often associ-
–– Normal serum albumin
ated with vitamin A, vitamin D, thiamine, and zinc
–– No edema
deficiency:
–– Hypoglycemia
• Stunted growth, low height for age: –– Hypotension, bradycardia, thermolabile
–– Associated with chronic malnutrition • Marasmic kwashiorkor:
–– Decreased fat and lean body mass –– Elements of both kwashiorkor and
marasmus
21 Nutrition 751
Vegetarian Diets –– Inflammation of the bowel due to inflam-

matory bowel disease or infections
Can generally support normal growth and develop- –– Intestinal lymphangiectasia, primary (con-
ment, but require extra careful attention to genital) or secondary (cardiac disease or
nutrition: increased retroperitoneal lymph nodes)
–– Post-Fontan procedure
• Semi-vegetarian—occasionally consume –– Giardiasis
meat, fish, or chicken. –– Malignancy
• Pescatarian—consume fish and shellfish and –– Cirrhosis
no meat. • Treatment:
• Lacto-ovo-vegetarian—consume eggs, milk –– Nutritional—low long chain fat, high-pro-
and milk products, and no meat. tein, and high medium-chain triglyceride
• Macrobiotic—consume whole grains, fruits, (MCT)-containing diet.
vegetables, beans, seaweed, and white meat –– Identify primary cause and treat.
or white fish.
• Vegan—consume no animal products of any
sort: actose Intolerance (See Also Chap.
L
–– Requires care that all nutritional needs are 22 Gastroenterology)
met.
–– Multivitamin with minerals is helpful to Milk protein allergy is not lactose intolerance:
prevent specific deficiencies for which they
are at risk. • Lactose intolerance is caused by a decrease in
–– At risk, especially, of inadequate consump- the disaccharidase lactase.
tion of the following: • Milk protein allergy is caused by immuno-
◦◦ Inadequate energy globulin response to cow’s milk protein:
◦◦ Omega-3 fatty acids –– IgE mediated:
◦◦ Protein ◦◦ Can occur at any age.
◦◦ Iron ◦◦ Reaction occurs immediately after
◦◦ Zinc ingestion.
◦◦ Calcium ◦◦ Skin, oropharyngeal, respiratory, GI
◦◦ Vitamin D tract, and/or cardiovascular signs and
◦◦ Vitamin B12 symptoms. Symptoms can be mild or
life-threatening.
◦◦ Diagnose with IgE antibodies to cow
Protein-Losing Enteropathy milk (see also Chap. 11 Allergy and
Immunology).
• Severe protein loss from the GI tract resulting –– Non-IgE mediated:
in hypoalbuminemia and often fat-soluble ◦◦ Delayed onset, more than 2 h after
vitamin deficiencies. ingestion.
• Assess with fecal alpha-1-antitrypsin. ◦◦ Primarily occurs in infants.
• Some common causes: ◦◦ Most commonly, infants less than
–– Gastritis such as Ménétrier disease, lym- 6 months who have blood in stools.
phocytic gastritis, Helicobacter pylori ◦◦ Additional symptoms can be vomiting,
gastritis diarrhea, failure to thrive, and
–– Milk protein allergy hypoalbuminemia.
–– Celiac disease
752 S. S. Baker
• Diagnosis: ◦◦ Assess with sweat chloride, fecal fat,

–– History and fecal elastase—for pancreatic insuf-
–– Gold standard: double-blind, placebo-con- ficiency, C-reactive protein (CRP),
trolled food challenge under clinical super- erythrocyte sedimentation rate (ESR),
vision; rarely done CBC with white cell differential, serum
–– Open challenge, most common IgA, and transglutaminase IgA. Consider
thyroid function tests.
◦◦ Stool for calprotectin, blood, white
Failure to Thrive blood cell (WBC), giardia antigen.
–– Increased losses:
Failure to thrive (FTT), more recently called fal- ◦◦ Brain tumor, allergy, malignancy.
tering growth, often is the result of inadequate ◦◦ Vomiting, diarrhea (may be caused by
nutrition: increased intake of juices and candies
with a high osmotic load).
• Growth faltering in infants is described as
◦◦ Assess with history, fecal alpha-1-anti-
weight gain less than the second percentile
trypsin, and fecal calprotectin.
for gestational corrected age and decreased
velocity of weight gain.
• In children, described as decreased growth Refeeding Syndrome
velocity.
• Causes: • Occurs when undernutrition is being treated—
–– Inadequate intake: nutritional rehabilitation.
◦◦ Most common reason. • Dangerous, can be associated with cardiac
◦◦ Caused by many possible problems: standstill.
poverty, psychosocial or behavioral • Highest risk is during the first 1–2 weeks of
problems, beliefs about foods that trans- rehabilitation.
late into dietary restrictions, congenital • Abnormalities:
anomalies (cleft lip/palate), intrauterine –– Hypophosphatemia, hypokalemia
alcohol exposure, neurological prob- –– Vitamin (especially thiamin) deficiencies
lems affecting oral motor skills, lead –– Hemolysis, rhabdomyolysis
poisoning, infections, any disease that • Management:
may cause decreased appetite and hence –– Correct electrolyte abnormalities.
inadequate intake. ◦◦ NOTE: All serum values can be normal
◦◦ Assess with history, including dietary prior to starting nutritional rehabilita-
recall. tion; this is not necessarily reassuring.
◦◦ Rule out organic cause such as a brain ◦◦ Repeat electrolytes, phosphorus, and
tumor, chronic constipation, and neuro- magnesium as macronutrient supple-
developmental disorders. mentation begins.
–– Increased requirements: –– For nutrition, “start low and go slow”; initially
◦◦ Malabsorption as occurs in cystic fibrosis, provide approximately resting energy expen-
celiac disease, pancreatic insufficiency diture; avoid rapid increases in caloric intake.
(Shwachman-Diamond syndrome). Nutrition can be PO, enteral, or intravenous.
◦◦ Chronic infections such as tuberculosis, –– Monitor serum phosphorus, electrolytes,
recurrent urinary infections. vitamins, and minerals.
21 Nutrition 753
–– Provide supplemental phosphorus, potas- C hronic Liver Disease

sium, and magnesium as indicated by
serum values. • Do not restrict food; do not restrict protein:
–– Supplement with vitamins and minerals. –– At risk of protein energy malnutrition
–– At risk of specific deficiencies:
◦◦ Thiamine
SPECIFIC CONDITIONS ◦◦ B12
REQUIRING NUTRITIONAL ◦◦ Folic acid
◦◦ Fat-soluble vitamins, A, D, E, K
SUPPORT
◦◦ Zinc
In every situation, malnutrition is a comorbidity ◦◦ Selenium
leading to increased morbidity and mortality. ◦◦ Magnesium
Malnutrition occurs because of decreased appetite • Monitor:
in chronic disease and increased requirements. –– Electrolytes
Careful attention to growth, energy, and protein –– Albumin
intake as well as vitamin, mineral, and trace ele- –– Fat-soluble vitamins
ment status is important. –– Prothrombin time, INR
• Supplement:
–– Calories—may require enteral feedings.
Cystic Fibrosis (Also See Chaps. 20 –– Protein (do not limit protein).
and 21 Pulmonology and GI) –– Vitamins and minerals.
–– Give one dose of 5 mg vitamin K IM if pro-
• Recommendation: vitamin A, D, E, and K longed PT or INR.
supplementation and high-protein and high- – – Use enteral feeding if cannot consume ade-
energy (aim for 150% of DRI) intake quate nutrition by mouth.
Viral Gastroenteritis Heart Failure
• Oral rehydration solution is the treatment of Heart failure is caused by structural or functional
choice for children with dehydration caused disorders, of which there are many:
by acute viral gastroenteritis.
• Early refeeding is associated with a shorter • At risk of the following:
duration of diarrhea. Studies have not shown –– Protein energy malnutrition
an increase in vomiting or diarrhea following –– Acidosis—correct
early refeeding. –– Iron deficiency with or without anemia
• The banana, rice, applesauce, and toast • Monitor:
(BRAT) diet has not been studied and is not –– Weight
currently recommended. –– CBC
• Lactose reduction has shown some benefit in –– Electrolytes
reducing the duration of diarrhea in hospital- –– Minerals
ized patients; however, there are no data to –– Albumin
support lactose reduction in children in the –– Vitamins, especially B vitamins
outpatient setting. • Supplement:
754 S. S. Baker
–– Increased caloric needs (120 kcal/kg/day) • Nutritional treatment:

to achieve optimal growth—consider tube –– NG or nasojejunal tube feeding if there’s
feeds. gastroparesis, tube for enteral nutrition
–– Vitamins. support on entering ICU.
–– Minerals. –– Avoid parenteral nutrition as much as pos-
–– Electrolytes as needed. sible, but if necessary, supply centrally.
Renal Disease Malignancies

• At risk of the following: • There are many different types of cancers;
–– Protein energy malnutrition nutritional risk varies with type, treatment,
–– Vitamin and mineral deficiencies, espe- and host factors:
cially vitamin D –– Lower risk:
–– Hyperphosphatemia, hyperkalemia ◦◦ Standard-risk leukemia
–– Iron deficiency anemia ◦◦ Early-stage tumors
–– Osteopenia –– Higher risk:
• Nutritional treatment: ◦◦ Solid tumors, especially of the head and
–– Protein (100–140% of DRI) and energy to neck
achieve growth; use supplements if neces- ◦◦ Advanced stage of malignancy
sary; if cannot meet energy requirements ◦◦ Relapsed disease
PO, consider tube feeding. –– Obesity risk posttreatment
–– Supplement with multivitamins, minerals, • Common themes:
and trace elements. –– Decreased appetite, mucositis—decreased
–– Low-potassium and low-phosphorus diet. intake
–– Limit sodium to DRI. –– Surgery, malabsorption, diarrhea, vomit-
–– Total calcium intake 100–200% of DRI. ing—increased nutrient requirements
–– Iron to correct iron deficiency anemia. –– Chemotherapy—decreased appetite, muco-
sitis, renal compromise, vomiting, diarrhea
–– Radiation—decreased appetite, mucositis,
Burns renal compromise, vomiting, diarrhea
• Nutritional support:
• At risk of the following: –– Low threshold for enteral feedings.
–– Increased energy and protein –– Parenteral nutrition only if absolutely
requirements: necessary.
◦◦ Metabolic rate increases proportionally –– Supplement with vitamins, minerals, and
with burn size = increased energy trace elements.
expenditure. • Monitor:
◦◦ Massive protein and lipid catabolism. –– Anthropometrics, weight, mid-arm muscle
◦◦ Total body protein loss. circumference for estimation of lean body
◦◦ Muscle wasting. mass unless MRI/DXA is available for
◦◦ Peripheral insulin resistance. estimation of body composition
◦◦ Increased body temperature. –– Electrolytes, vitamins, minerals, and trace
◦◦ Synthesis of acute-phase proteins. elements, including zinc, especially if diar-
◦◦ Infection of burned area—sepsis. rhea is present
21 Nutrition 755
Allergies • Supplement:
–– If unable to feed, needs gastrostomy tube
Nutrition must prevent reactions to foods and sup- –– If able to feed, may need pureed foods
port optimal growth and development:
• At risk of inadequate intake of low-quality F amily and Cultural Practices

foods:
–– Depends on the kinds and number of food • Food fads vary overtime, rarely grounded in
allergens—many protein-rich foods are good nutrition.
common allergens (cow milk, fish, soy, • When talking with families, focus on the DRI
egg). and USDA dietary guidelines.
–– Depends on the palatability of the elimina- • Supplements from nutrition stores, “nutra-
tion diet. ceuticals,” are not regulated by federal law:
–– Depends on the acceptability of the diet to –– Contents of package can vary or not be
the child. present at all.
• Supplement: – – Package can contain non-identified harm-
–– Multivitamin with minerals and trace ful contaminants.
elements –– When recommending supplement, use
–– Additional protein and calories with com- only those with the United States
mercial supplements if diet is highly Pharmacopeia (USP) designation that
restricted demonstrates they meet these standards.
–– Tube feed if the child refuses diet
PEARLS AND PITFALLS
Neurological Impairment
• Breastfeeding is not contraindicated in cases
• At risk: of mastitis, skin candidiasis, atopic dermati-
–– Children with cerebral palsy who cannot tis, gadolinium contrast for imaging studies,
easily feed themselves, chew, or hepatitis B, or hepatitis C.
swallow. • Zinc homeostasis is via the GI tract. Consider
–– Gastroesophageal reflux caused by poor zinc deficiency for children who have pro-
muscle tone, positioning in wheelchair. longed bout of diarrhea.
–– Constipation caused by poor muscle tone, • The first sign of vitamin A deficiency is night
inability to go to the toilet. blindness.
–– Children with minimal movement are at • When nutrition support is needed, use paren-
risk of obesity: teral nutrition as a last resort or only when the
◦◦ Enteral feeding products that supply GI tract has failed.
adequate fluids and DRI for vitamins • It may be necessary to present a new food 10
and minerals and can have an excess of or more times before a toddler will accept it.
calories for non- or minimally mobile Caution mothers not to take the first few
children. refusals as nonacceptance.
◦◦ If there’s decrease in enteral feeding • For breastfed infants with blood in stools,
product to reduce caloric intake, there’s continue breastfeeding, remove dairy from
a need to provide additional water, vita- mother’s diet, supplement her with calcium,
mins, minerals, and trace elements. and reassess before breastfeeding is stopped.
756 S. S. Baker
Suggested Reading Sciences, Engineering, and Medicine. Health

and Medicine Division. (n.d.) Last updated 16
American Academy of Pediatrics Committee on Jan 2018. Accessed 26 Nov 2018.
Nutrition. In: Kleinman RE, Greer FR, editors. Duggan C, Watkins JB, Koletzko B, Walker WA,
Pediatric nutrition. 7th ed. Elk Grove: American editors. Nutrition in pediatrics: basic science,
Academy of Pediatrics; 2014. clinical applications. 5th ed. Shelton: People’s
Dietary reference intakes tables and application. Publishing House; 2016.
http://nationalacademies.org/hmd/Activities/ Stipanuk MH, Caudill MA. Biochemical, physi-
Nutrition/SummaryDRIs/DRI-Tables.aspx. ological and molecular aspects of human nutri-
Washington DC: National Academies of tion. 4th ed. St. Louis: Elsevier/Saunders; 2019.
Gastroenterology
22
Robert D. Baker
ABDOMINAL PAIN unctional Abdominal Pain (Rome IV

F
Criteria)
Age-Appropriate Differential
Diagnosis of Acute Abdominal Pain • Rome criteria are developed as an international
(Tables 22.1, 22.2, 22.3, 22.4, and 22.5) effort to diagnose and treat functional gastroin-
testinal (GI) disorders based on scientific data.
• Acute abdominal pain can originate outside The criteria are determined by a panel of
the abdomen experts and disseminated by the Rome
–– Lower lobe pneumonia
–– Pharyngitis
Table 22.1 Cause of acute abdominal pain in neonates
–– Urinary tract infection (0–2 months)
• Most abdominal pain that comes to medi- Serious Less serious
cal attention is short in duration and not Common NEC Colic
life-threatening Adhesions
• Constipation is a frequent cause of acute Uncommon Volvulus Dietary protein allergy
abdominal pain, but a child with constipation Testicular torsion
may have additional reasons for pain
• Only 2% of episodes of acute abdominal pain
require surgery Table 22.2 Causes of acute abdominal pain in infants
(2 months to 2 years)
• Age of onset, concomitant signs and symp-
Serious Less serious
toms, history, and physical exam lead to the
Common Foreign body ingestion Constipation
correct disposition Trauma Gastroenteritis
• Laboratory tests and imaging are often help- Viral illness
ful, even if normal Dietary protein
allergy
Urinary tract
infection
Uncommon Adhesions Hepatitis
Hemolytic uremic
syndrome
Hirschsprung disease
Intussusception
R. D. Baker (*) Incarcerated hernia
Department of Pediatrics, Jacobs School of Medicine and Sickle cell crisis
Biomedical Sciences, University at Buffalo, State University of
New York, Amherst, NY, USA Tumor
e-mail: rbaker2@buffalo.edu

758 R. D. Baker
Table 22.3 Causes of acute abdominal pain in preschool Table 22.5 Causes of acute abdominal pain in adolescents
children (2–5 years) (12–18 years)
Serious Less serious Serious Less serious
Common Appendicitis Constipation Common Adhesions Constipation
Foreign body ingestion Viral illness Appendicitis Viral illness
Intussusception Gastroenteritis Diabetic ketoacidosis Gastroenteritis
Trauma Pharyngitis Inflammatory bowel Pharyngitis
Urinary tract disease Urinary tract
infection Hemolytic uremic infection
Pneumonia syndrome Pneumonia
Uncommon Adhesions Henoch-Schönlein Pelvic inflammatory Ruptured ovarian
Hemolytic uremic purpura disease cyst
syndrome Hepatitis Trauma
Intra-abdominal Uncommon Hemolytic uremic Abdominal
abscess syndrome migraine
Diabetic ketoacidosis Perforated ulcer Cholecystitis
Ovarian torsion Primary bacterial Henoch-Schönlein
Sickle cell crisis peritonitis purpura
Tumor Intra-abdominal Hepatitis
abscess Familial
Myocarditis/ Mediterranean fever
Table 22.4 Causes of acute abdominal pain in children pericarditis Urolithiasis
(6–11 years) Pancreatitis
Serious Less serious Sickle cell crisis
Common Adhesions Constipation Ovarian/testicular
Appendicitis Viral illness torsion
Diabetic ketoacidosis Gastroenteritis Ectopic pregnancy
Inflammatory bowel Pharyngitis Tumor
disease Urinary tract
Trauma infection
Dysmenorrhea Functional Dyspepsia (H2a)
Pneumonia
Uncommon Hemolytic uremic Abdominal migraine
syndrome Cholecystitis
• Postprandial fullness, early satiety, epigastric
Perforated ulcer Henoch-Schönlein pain, or burning not associated with defeca-
Primary bacterial purpura tion, no other medical reason for symptoms
peritonitis Hepatitis • Postprandial distress syndrome: Postprandial
Hemolytic uremic Familial nausea, excessive belching, and upper abdom-
syndrome Mediterranean fever
Intra-abdominal inal bloating
abscess • Epigastric pain syndrome: Epigastric pain or
Myocarditis/ burning that interferes with normal activity
pericarditis
Pancreatitis
Ovarian/testicular
torsion
Irritable Bowel Syndrome (IBS) (H2b)
Sickle cell crisis
Tumor • Abdominal pain at least 4 days a month for at
least 2 months
–– Related to defecation: Change in fre-
Foundation (non-profit), Raleigh, NC (https:// quency, change in form
theromefoundation.org/). In the following –– Diarrhea dominant, constipation dominant,
outline, Rome IV criteria are referenced and and mixed types. There is also an unspeci-
denoted in parentheses. fied type
22 Gastroenterology 759
Diagnosis of IBS Cyclic Vomiting (Abdominal

• Careful history and physical exam may be Migraine)
sufficient to make diagnosis. Can be simple
constipation Background
• Fecal calprotectin differentiates IBS from GI • Episodes of vomiting interspersed with well
inflammation interval
• Caution should be taken not to overlook • Idiopathic cyclic vomiting may be migraine
infection (including Helicobacter pylori and equivalent
Giardia intestinalis)
• Celiac disease (even with constipation), mal- Clinical presentation
absorption (lactose intolerance) and inflam- • Prodromes: Pallor, intolerance to noise/light,
matory bowel disease (IBD) can mimic IBS nausea, lethargy, headache, or fever
• Precipitants: Excitement, infection, stress,
Treatment of IBS and others
• Educate parents and child that irritable bowel • Average 12 episodes per year
syndrome is a chronic illness that cannot be • Each episode may last 1–3 days with 4 or
cured more emesis per hour
• Reassure them that it is not a life-threatening
condition and does not lead to physical Diagnosis
impairment • Diagnosis of exclusion: Lab based on history
• Behavioral treatment with focus on coping and physical examination, endoscopy, con-
skills trast upper GI, brain MRI, and metabolic
• Dietary fiber supplementation and stool soft- studies
eners for constipation
• Few drug treatment trials in children—cau- Treatment
tion with any medication in children • Hydration and ondansetron
• Antispasmodics may help in moderate to severe • Sumatriptan can abort episodes of cyclic vom-
cases, e.g., peppermint oil and dicyclomine iting in children and adults
Prevention
Abdominal Migraine (H2c) • Cyproheptadine or amitriptyline
• Paroxysmal episodes of severe abdominal F unctional Abdominal Pain: Not Otherwise

pain Specified (H2d)
• Lasting 1 h or more • Usually a teenager
• Usually mid-abdominal • Epigastric discomfort, early satiety, bloating,
• Episodes separated by weeks to months nausea, belching
• Stereotypic pattern specific for individual • Associated with meals
• Symptoms (not explained by other medical • No relationship to defecation
conditions) including anorexia, nausea, vom- • Pathophysiology not understood
iting, headache, photophobia, and pallor • Episodic or continuous abdominal pain at
least 4 times a month
Treatment
• Not associated with physiologic events
• After the episode is over, future episodes may
(eating, menses)
be prevented with cyproheptadine
760 R. D. Baker
• Not sufficient criteria for IBS protein, albumin, glucose, celiac panel,
• Not explained by other medical conditions thyroid panel
Treatment Helpful stool tests:

• Reassurance, empathy, and education • Stool for occult blood, fecal calprotectin,
• Cognitive behavioral therapy (CBT) and hyp- fecal pancreatic elastase, G. intestinalis
notherapy have been shown to be effective for antigen, H. pylori antigen
abdominal pain
• Pharmacologic treatment is mainly empiric, Helpful imaging:
e.g., prokinetic agents • Ultrasound (gallbladder disease, ovarian
cysts, dilated biliary system, pancreatic
disease)
Chronic, Recurrent Abdominal Pain –– Ultrasound will be positive less than 1% of
the time
Clinical manifestations of chronic recurrent • Plain film of abdomen for constipation (radi-
abdominal pain and management ologist dependent) dilated loops
• Most children with chronic abdominal pain • Upper GI series for malrotation, upper GI
will have “functional GI disease.” Work-up obstruction
should be minimal. • Computed tomography (CT) scan for bowel
wall thickening, abscesses, partial
Potential alarm features that may trigger fur- obstruction
ther investigations (Table 22.6) [1] • Magnetic resonance enterography (MRE)
Helpful laboratory tests: similar to CT with less radiation exposure
• Complete blood count (CBC), differential,
platelet count, erythrocyte sedimentation rate Age-appropriate differential diagnosis of recur-
(ESR), C- reactive protein (CRP), sodium, rent abdominal pain
potassium, chloride, carbon dioxide, blood • 2–5 years: Constipation, carbohydrate intol-
urea nitrogen (BUN), creatinine, alanine ami- erance, gastroesophageal reflux
notransferase (ALT), aspartate aminotrans- • 6–10 years: School phobia, indigestion and
ferase (AST), alkaline phosphatase, stomach irritation from dietary indiscretion,
gamma-glutamyl transpeptidase (GGT), total nonsteroidal anti-inflammatory drugs (NSAIDs),
acid and spicy foods, carbonated beverages
• 11–21 years: School phobia, indigestion and
Table 22.6 Warning signs and symptoms of an organic stomach irritation from dietary indiscretion,
cause for chronic abdominal pain
NSAIDS, acid and spicy foods, carbonated
Recurrent vomiting Chronic diarrhea
beverages, hepatitis
Perianal disease Dysphagia
Oral lesions Skin rashes
Persistent localized pain Decrease in linear
growth Referred Abdominal Pain
Unexplained weight loss Blood in stool
Fever, if not explained Abdominal mass • Referred abdominal pain is pain experienced
Enlarged liver or spleen Abdominal guarding at a distance from the source of the pain
Family history of inflammatory Family history of celiac
bowel disease disease
• Children less than 5 years of age are poor at
Arthritis Urinary symptoms localizing pain
Delayed puberty Dysmenorrhea, • They frequently indicate the periumbilical
amenorrhea area for pain, abdominal and sometimes
From Hymans et al. [1], with permission extra-abdominal
• Older children are more precise in localizing Clinical presentation

pain • Rapidly progressing from diffuse abdominal
• Visceral pain comes from the intra-abdomi- discomfort to point tenderness with perito-
nal organs. Nerve fibers from these organs neal signs in 12 h
respond to distention, but not cutting, tearing, • Localized abdominal tenderness is the single
or inflammation. Pain from visceral organs is most reliable finding in the diagnosis of
poorly localized appendicitis
–– Pain from the stomach, duodenum, liver, • Guarding: gentle finger percussion is a better
and pancreas is perceived to be epigastric test for peritoneal irritation
–– Pain from the small bowel, most of the • Rovsing sign
colon, and appendix is felt in the –– RLQ pain with palpation of the left lower
mid-abdomen quadrant (LLQ); referred rebound tender-
–– Pain from the lower colon and genitouri- ness when palpating the LLQ
nary tract is localized in the suprapubic area • Obturator sign
• Somatic pain comes from the peritoneum and –– RLQ pain with internal and external rota-
the abdominal wall. Excitation of somatic tion of the flexed right hip
fibers transmit tearing, cutting, and inflam- • Psoas sign
matory sensations. Localization is more pre- –– RLQ pain with extension of the right hip or
cise than visceral pain, but referred pain with flexion of the right hip against
occurs, especially to dermatomes correspond- resistance
ing to somatic nerve excitation • Dunphy sign
–– Irritation of the diaphragm results in shoul- –– Sharp pain in the RLQ elicited by a volun-
der pain tary cough
–– Pleural irritation can be perceived as • Markle sign
abdominal pain –– Pain elicited in a certain area of the abdo-
–– Pain from kidney stones is felt in the groin men when the standing patient drops from
area standing on toes to the heels with a jarring
landing
Acute Appendicitis Laboratory

• White blood cell (WBC) count elevated but
Background can be normal within the first 24 h, but with a
• Most common abdominal surgical emergency left shift
in childhood, but rare before 5 years of age • Left shift plus abnormal elevated CRP is 94%
• MANTRELS (mnemonic) specific
–– Migrating
–– Anorexia Imaging studies
–– Nausea/vomiting • Point of service ultrasound has become the
–– Tender in right lower quadrant (RLQ) diagnostic modality of choice
–– Rebound • Ultrasound diagnostic criteria:
–– Elevated temperature –– Wall thickness > 6 mm
–– Leukocytosis –– Lack of compressibility
–– Shift to left –– Luminal distention
762 R. D. Baker
Appropriate diagnostic evaluation when appen- Management

dicitis is suspected • Because of the danger of midgut volvulus,
• Nil per os (NPO), intravenous (IV) hydration, even asymptomatic malrotations should be
pain medication surgically “fixed” with Ladd’s procedure
• Antibiotics before surgery, e.g., cefoxitin,
piperacillin/tazobactam, or imipenem/
cilastatin Volvulus
• CBC with differential and platelet count,
chemistries, CRP, and ESR Background
• Ultrasound; if equivocal—CT scan • Midgut volvulus is a surgical emergency
• Surgical consult because twisting around the mesenteric root
• If simple appendicitis—surgery can result in occlusion of the superior mesen-
• If not clearly acute appendicitis—observe— teric artery and subsequent ischemia of bowel
reevaluate from the distal duodenum to the mid-trans-
• If walled-off perforation or abscess, antibiot- verse colon
ics plus-minus drainage. Either no surgery or • If resection of the GI tract from the distal duode-
delayed surgery num to the mid-transverse colon is necessary,
• If “free perforation” or generalized peritoni- the child will be left with extremely short gut
tis—immediate surgery • 45% is a result of malrotation. Remainder is
idiopathic, due to adhesions or Meckel
diverticulum
Malrotation • Intestinal malrotation is often associated with
other congenital anomalies including hetero-
Background taxy syndrome, omphalocele, gastroschisis,
• Failure of normal rotation and fixation of GI congenital diaphragmatic hernia, esophageal
tract during organogenesis resulting in the atresia, renal anomalies, and cardiac
cecum being in the right upper quadrant anomalies.
(RUQ) and free to fold and unfold • Heterotaxy syndrome: failure of normal
• The small bowel is on the right side of the embryological rotation results in abnormally
abdomen, so the root of the mesentery is positioned organs in the chest and abdomen
narrow
• Ladd’s bands extend from the cecum to the Clinical presentation
abdominal wall, crossing the duodenum • Symptoms are nonspecific and malady is rap-
• Rotation abnormalities may be as frequent as idly progressive
1 in 100 live births. Many go undetected or • Abdominal pain
are picked up incidentally • Bilious vomiting (ominous presentation sug-
gestive of bowel obstruction)
Clinical features • Abdominal distention
• Intermittent abdominal pain
• Intermittent bilious or non-bilious vomiting Investigations
• Labs are nonspecific
Diagnosis • Radiograph usually proximal dilation and
• Upper GI series radiograph showing abnor- distal paucity of gas
mal position of the cecum, abnormal position • Plain film may not show classic picture
of the ligament of Treitz, and/or partial • Upper GI series is 96% sensitive; shows
obstruction of the duodenum “corkscrew sign”
Management Diagnosis
• Urgent surgical consultation • Early diagnosis via ultrasound (close to 100%
• Fluid resuscitation, evacuation of the stom- accurate) means that triad seldom encoun-
ach, and proceed to surgery quickly tered anymore
• Other types of volvulus
–– Stomach, organo-axial, and Management
mesentero-axial • Air enema (most often reduced with air
–– Sigmoid, “coffee bean” on plain film enema); infrequently, surgery
• If air enema fails, a surgery must be per-
formed to reduce intussusception
Intussusception
Background cute Pancreatitis
A
• Invagination of proximal segment of bowel
into distal segment Clinical and laboratory features associated
• Occurs at any age but most common pancreatitis
6–36 months • Abdominal pain (older child), bloating
• Usually ileocolic but can have other lead (younger child)
points • Amylase and/or lipase 3 times the upper limit
• Outside this age group, suspect unusual etiol- –– Amylase can be from salivary glands,
ogy, e.g.: gonads, or from intestinal obstruction;
–– Meckel diverticulum while lipase is more specific to the
–– Enlarged mesenteric lymph node pancreas
–– Benign or malignant tumors of the mesen- • Ultrasound for stones and ducts, CT for com-
tery or of the intestine, including lym- plications, necrosis, hemorrhage, pseudocyst
phoma, polyps, ganglioneuroma, • Endoscopic retrograde cholangiopancreatog-
hamartomas associated with Peutz-Jeghers raphy (ERCP) for stone removal
syndrome • ERCP and magnetic resonance cholangio-
–– Mesenteric or duplication cysts pancreatography (MRCP) to delineate
–– Submucosal hematomas, which can occur anatomy
in patients with Henoch-Schönlein purpura
(HSP) and coagulation dyscrasias Management
–– Ectopic pancreatic and gastric rests • Pain control
• Nutrition enteral feeds
• Fluid therapy (if adequate kidney function,
Clinical presentation give at least 2 times maintenance fluids)
• Classic triad • In most cases, no total parenteral nutrition
–– Severe intermittent abdominal pain (TPN), no antibiotics
–– Sausage-shaped abdominal mass
–– Currant jelly stools (late presentation sug-
gest vascular compromise) Recurrent Pancreatitis
• Vomiting (can be bilious)
• Lethargy (out of proportion of abdominal • No underlying etiology found in one-third of
pain) cases
764 R. D. Baker
• Toxic-metabolic: Medications, hypercalce- • Symptomatic stones are most often treated

mia, hyperlipidemia, post graft-versus-host with surgery. Dissolution and lithotripsy are
disease, chronic renal failure, organic used less often
compounds
• Genetic: PRSS1 (protease serine 1) mutation,
CFTR, SPINK1 (serine peptidase inhibitor C holecystitis
kazal type 1), CPA1 (carboxypeptidase A1)
mutation, CTRC (chymotrypsin C) mutation Background
• Autoimmune: Isolated and syndromic (IgG4) • Inflammation of the gallbladder secondary to
• Anatomic: Pancreas divisum, annular obstruction—gallstones (usual), edema,
pancreas external compression
–– These anatomic anomalies are disputed as
causes of pancreatitis
• RUQ pain, sometimes radiating to back and
• After severe acute pancreatitis
accompanied by vomiting
• Murphy’s sign—pain on palpation in RUQ. Can
Cholelithiasis be elicited with ultrasound transducer
–– Classic description of Murphy’s sign
Risk factors associated with the development of includes having the patient exhale and then
cholelithiasis palpating deeply below the right ribcage,
• Predisposing factors: Hemolytic disease, in the mid clavicular line; when the patient
obesity-related, metabolic syndrome, prema- inhales, the gallbladder moves down
turity, necrotizing enterocolitis, congenital against the examiner’s fingers, causing
heart disease, cystic fibrosis, TPN-related, pain and interruption of inhaled breath.
ethnicity (Amerindian) , ileal disease, and The same procedure on the left side of the
ileal resection abdomen will not produce the same effect.
• Gene: Lith1, Lith2 cholesterol formation. • Fever and jaundice present in 25–30%. More
APOBEC-1 when downregulated associated common in young children
gallstones. FXR (farnesoid X receptor) • Pain increases usually over a week, but mild
related to gallstone formation. Mutation in discomfort may have been present for years
ABCB4 described in adults with stones
• Other genes: ABCG5, ABDG8, CYP7A1, Imaging studies
CCK1R, and more • Ultrasonography
• Black pigmented stones associated with –– Can show the presence of stones and a
hemolytic disease. Brown pigmented stones thickened gallbladder wall with possible
associated with infection. Cholesterol stones gallbladder dilation
are found in obesity and TPN. – – The ultrasonographer can produce a posi-
tive Murphy’s sign with the transducer
Diagnosis and treatment • Hepatobiliary scintigraphy
• Diagnosis via imaging: Radiography, ultra- –– If the gallbladder cannot be visualized
sound, CT scan
• Gallstones in infants do not necessarily require Laboratory
treatment. 50% resolve spontaneously • Elevated liver enzymes, especially GGT and
• If complications are likely (hemolytic dis- alkaline phosphatase
ease) or are likely to be severe (cystic fibro- • The WBC count and direct bilirubin are usu-
sis), elective cholecystectomy indicated ally elevated
• The amylase value can be elevated, making it –– Difficult to diagnosis

harder to know if the problem is cholecystitis ◦◦ In face of fever, increased liver tests—
or pancreatitis treat empirically with IV broad-spec-
trum antibiotics
Treatment • Primary sclerosing cholangitis—extraintesti-
• Bowel rest, intravenous pain control, and IV nal complication of IBD
fluids –– No accepted treatment—recurs post liver
• If fever is present or the child looks ill or transplant
unstable, antibiotics are needed for enteric –– Some have advocated long-term treatment
bacteria with vancomycin
• The timing of curative cholecystectomy is –– Crossover variety with autoimmune
best determined by the surgeon hepatitis
Complications
• Perforation of the gallbladder, with peritoni- Acalculous Cholecystitis
tis or abscess formation
• Typically occurs during a significant systemic
illness such as sepsis
Choledocholithiasis (Common Bile • Illness requiring a stay in the intensive care
Duct Stone) unit
• Stone obstructing the biliary duct system

• Jaundice with or without pain VOMITING
• Progresses to symptoms similar to cholecys-
titis, RUQ pain, fever, vomiting • Vomiting is the result of a complicated reflex
• Pancreatitis may be present if stone blocks in response to a number of stimuli
the pancreatic duct –– The forceful expulsion of gastric contents
• Leukocytosis, elevated AST, ALT. Elevated through the oral cavity
alkaline phosphatase and GGT. Elevated • Must differentiate from regurgitation, which
amylase and lipase if pancreas involved is not forceful
• Dilated biliary ductal system bile: Ultrasound, –– Clinically, sometimes difficult to make this
MRCP, or ERCP distinction
• The emetic reflex has 3 phases. Phases can
Diagnosis and treatment occur in sequence or independently of each
• Diagnosis via imaging other:
–– Ultrasound, MRCP, ERCP –– Prodromal period called nausea
–– ERCP allows stone retrieval, stent place- –– Retching
ment, and sphincterotomy—not always –– Vomiting
possible in a small child • Emetic reflex has afferent limb, central inte-
gration, efferent limb
• Initiated by pain, inflammation, toxins, motion,
Cholangitis (Rare in Pediatrics) pregnancy, radiation exposure, postoperative
conditions, unpleasant emotions, etc.
• Post Kasai portoenterostomy
• Serotonin receptor antagonists in the preven-
–– Roux-en-Y loop allows pathway for bacte-
tion and treatment of vomiting
ria to enter cholangioles
766 R. D. Baker
–– Vomiting is initiated through release of –– Viral: Rotavirus, calicivirus, (HuCV) noro-

5-HT (serotonin) in small intestine, bind- virus, sapovirus, Snow Mountain virus,
ing to 5-HT3 receptors that initiate signals hepatitis E virus, enteric adenovirus, astro-
in the afferent vagal nerve that activates the virus, and others
vomiting reflex – – Bacteria: Shigella, Salmonella, Yersinia,
–– 5-HT3 antagonists (ondansetron and oth- Campylobacter, Vibrio, diarrheagenic
ers) block this pathway Escherichia coli, Clostridium, and others
• Other important neurotransmitter receptor ◦◦ Clinical symptoms are nausea, vomit-
sites exist (muscarinic, M1: dopamine, D2; ing, diarrhea, and abdominal pain
histamine, H1; neurokinin, NK1; and sub- ◦◦ Organisms infecting the stomach and upper
stance P) GI tract associated with more nausea and
• Vomiting can be initiated via many mecha- vomiting and less diarrhea, while with
nisms and systems colon involvement diarrhea predominates
–– GI, neurologic, renal, urogenital, psychiatric ◦◦ Even among organisms of the upper GI
–– Associated with infections, allergies, ana- tract there is a varying degree of vomit-
tomic abnormalities ing (norovirus was originally called
–– Acute and chronic “winter vomiting sickness”)
–– Motion and emotions
• Vomiting and infection Age-appropriate differential diagnosis of vom-
–– Acute infection of the stomach, small iting (Table 22.7) [2]
bowel and colon. Usually viral, but also • Neonate and young infant
due to bacteria, fungi, and others –– Gastroesophageal reflux disease (not true
vomiting, rather, regurgitation)
Table 22.7 Causes of vomiting in children

Infant Child Adolescent
Common
Gastroenteritis Gastroenteritis Gastroenteritis
Gastroesophageal reflux Systemic infection GERD
Overfeeding Gastritis Systemic infection
Malrotation/volvulus, pyloric stenosis, Toxic ingestion Toxic ingestion
intussusception) Pertussis syndrome Gastritis
Pertussis syndrome Medications Sinusitis
Otitis media Reflux (GERD) Inflammatory bowel disease
Meningitis Otitis media Appendicitis
Pyelonephritis Meningitis Migraine
Pneumonia Pregnancy
Malrotation/volvulus Ipecac abuse, bulimia
Intussusception Concussion
Inguinal hernia
Rare
Hydrocephalus/shunt malfunction Hepatitis Hepatitis
Brain tumor Pancreatitis Pancreatitis
Subdural hematoma Brain tumor Brain tumor
Hirschsprung disease Cyclic vomiting Cyclic vomiting
Paralytic ileus Duodenal hematoma Inguinal hernia
Metabolic Metabolic Superior mesenteric artery syndrome
Adrenal hyperplasia Surgical adhesions
Addison disease Biliary colic
Renal tubular acidosis Renal colic
Ureteropelvic junction obstruction Diabetes ketoacidosis
Adapted from Nelson et al. [2], with permission
GERD Gastroesophageal reflux disease
–– Food protein-induced enteropathy (FPIES) • Adolescent

–– Hypertrophic pyloric stenosis –– Functional dyspepsia
–– Intestinal obstruction: Malrotation, volvu- –– Functional nausea and vomiting
lus, atresias, Hirschsprung disease –– Appendicitis
–– Inborn errors of metabolism –– IBD
• Bilious vomiting in a newborn infant –– Pregnancy
–– Bilious vomiting in a neonate is usually an –– Bulimia, psychogenic vomiting
ominous symptom suggesting an obstruc- –– Rumination syndrome
tion distal to the second portion of the –– Cannabinoid hyperemesis syndrome
duodenum
–– Diagnosis is via imaging, plain film, ultra-
sound, and upper GI series ESOPHAGUS
–– Stomach should be evacuated, infant stabi-
lized, and plans for urgent surgery astroesophageal Reflux
G
• Projectile vomiting in a newborn infant in an Infant
–– True projectile vomiting is suggestive of an
upper small bowel obstruction. Be careful, • Infantile reflux is common (about 60% of
parents can describe forceful regurgitation infants)
as projectile • Non-forceful expulsion of gastric contents
–– Hypertrophic pyloric stenosis will be the • Can last up to 18 months of age
most common cause • Treat conservatively unless associated with
–– Uncommon causes: Foveolar hyperplasia, complications:
pyloric webs, pyloric atresia, antral web, –– Weight loss or poor weight gain
antral atresia, adrenal insufficiency –– Aspiration, especially with pneumonia
–– Pyloric web can present as a “windsock” –– Extreme irritability
abnormality
–– Diagnosis is by physical exam (visible Conservative treatment
peristalsis), ultrasound (mass, mucosal • Small, frequent feeds (may need extra calo-
thickening), upper GI series, and ries because of loss due to reflux)
endoscopy
–– Treatment: Evacuate the stomach, stabi-
lize, correct electrolytes, surgery. Dilation
via endoscopy sometimes possible, espe-
cially in foveolar hyperplasia
• Older infant and child
–– Gastroenteritis
–– Infections
–– Intussusception
–– Anaphylaxis
–– Adrenal crisis
–– Increased intracranial pressure
–– Cyclic vomiting
–– Migraine
–– Eosinophilic esophagitis or gastroenteritis
–– Child abuse
Fig. 22.1 Barium swallow image showing severe reflux
768 R. D. Baker
• Upright after meals for at least 15 min; burp Clinical presentation

well • Vomiting in the younger child
• Elevate the head of the crib, position on back • Food impaction in adolescents
• Trial of thickened formula or human milk • Esophageal strictures can occur
(one teaspoon rice cereal per ounce of fluid).
If helpful, continue. If not, stop Management
• For formula-fed infants, time-limited trial of • 75% respond to milk elimination
hypoallergenic formula (no more than 7 days) • Almost 100% respond to amino acid formula
• Can be treated with swallowed, poorly
Medical treatment absorbed steroids
• Continue conservative treatment • Relapse when the intervention is stopped
• Trial of H2RA acid suppression (ranitidine
and others)
• If not responding, consider further work-up Caustic Esophageal Injuries
Further work-up (Fig. 22.1) Background

• Upper GI radiograph to look for partial • Ingestion of caustic agents
obstruction • More predominant in males
• pH probe/impedance off medication to quan- • Age between 1 and 3 years is more common
tify reflux, on medication to assess efficacy of • Alkaline agents cause severe injuries rapidly
acid suppression after ingestion and more damage to:
• Gastric emptying scan (scintigraphy) –– Oropharynx
–– Can assess gastric emptying—not very –– Hypopharynx
reliable and not reproducible –– Esophagus (45%)
–– The scan may identify esophageal reflux • Acid agents cause more damage to the stom-
and aspirations ach after ingestion
–– The major diagnostic role is in the assess-
ment of pulmonary aspiration Clinical presentation
–– Patients should be rescanned after 24 h in • Dysphagia
order to assess delayed pulmonary soilage • Drooling
by refluxed gastric contents • Abdominal pain
• Hematemesis
• Respiratory distress
Further treatment
• If still not responding, especially not gaining Management
weight, transpyloric tube feedings • Avoid neutralizing agents, e.g., vinegar or
• Surgery as a last resort (fundoplication) sodium bicarbonate
• Endoscopy is indicated after 6 h to document
full extent of injuries
Eosinophilic Esophagitis (EE) • Endoscopy should not be later than 4 days
post-ingestion to minimize perforation
• Non-immunoglobulin E (IgE) immune-medi-
ated inflammatory process causing intense Complication
(> 15 eosinophils per high-powered field) • Esophageal stricture
infiltration of the esophageal mucosa
• Thought to be food antigen related
umination (Rome IV Rumination

R Diagnosis
Criteria [H1c]) • Plain film, ultrasound, or CT scan can con-
firm the diagnosis
Clinical diagnosis
• Repeated regurgitation with re-chewing or Management
expulsion of food that begins right after a • Endoscopic removal
meal and does not occur during sleep • Surgery if endoscopy is not successful
• Not preceded by retching • Lactobezoar usually resolve when feeding
• Cannot be explained by conditions, and an withheld for 24–48 h
eating disorder has been excluded
• Symptoms must be present for minimum of
2 months
oreign Body in the Esophagus
F
• Rumination can occur at any age, but fre- and Stomach
quently in teenage girls
Background
• Contraction of abdominal muscles with relax-
• Majority of cases between 6 months and
ation of the lower esophageal sphincter (LES)
3 years
• Characteristic high pressure “r-wave” on
• Coins and small toys are most common
motility studies
• Upper esophageal sphincter (UES) cricopha-
Associated medical conditions ryngeus is the most common site, and the
• Intellectual disability next is the LES
• Bulimia
• Psychological stress or psychological trauma
• 30% of cases are asymptomatic
Management • Any history of ingestion should be taken seri-
• Multidisciplinary approach ously and investigated even with no symptoms
• Primary focus on behavioral therapy and • Initial bout of choking, gagging, and cough-
biofeedback ing may be followed by salivation, dysphagia,
• Tricyclic antidepressants and nutritional sup- and refusal to eat
port may be necessary • Vomiting
• Pain in the neck, throat, or sternal notch regions
• Stridor, wheezing, cyanosis, or dyspnea if the
Bezoars foreign body impinges on the larynx
• Cervical swelling, erythema, and subcutane-
Background ous crepitations suggest perforation
• Accumulation of exogenous matter in the
stomach and intestine Diagnosis
• Trichobezoar, hair; phytobezoar, plants, ani- • Plain film anteroposterior and lateral neck,
mal material, and chewing gums; lactobezoar, chest and abdomen (wood, glass, plastic,
milk solids bone, and aluminum may be radiolucent)
Clinical presentation Timing of endoscopy in foreign body ingestions

• Gastric outlet obstruction complete or (Table 22.8) [3]
partial • Coin in the esophagus
• Anorexia, vomiting, weight loss, severe hali- –– Most coins pass into the stomach and
tosis, abdominal pain, and distension through the GI tract without incident
770 R. D. Baker
Table 22.8 Timing of endoscopy in foreign body ingestion

Type Location Symptoms Timing
Button battery Esophagus Yes or no Emergency
Gastric/SB Yes Emergency
No Urgent (if age < 5 and BB ≥ 20 mm)
Elective (if not moving)
Magnets Esophagus Yes Emergency (if not handling secretions)
No Urgent
Gastric/SB Yes Emergency
No Urgent
Sharp object Esophagus Yes Emergency (if not handling secretions)
No Urgent
Gastric/SB Yes Emergency (if signs of perforation, with surgery)
No Urgent
Food impaction Esophagus Yes Emergency (if not handling secretions)
No Urgent
Coin Esophagus Yes Emergency (if not handling secretions)
No Urgent
Gastric/SB Yes Urgent
No Elective
Long object (> 4 cm) Esophagus Yes or no Urgent
Gastric/SB Yes or no Urgent
Absorptive object Esophagus Yes Emergency (if not handling secretions)
No Urgent
Gastric/SB Yes or no Urgent
From Kramer et al. [3], with permission
BB Button battery, SB Small bowel. Emergency = Move to endoscopy as quickly as possible, < 2 h Urgent = Endoscopy
within 24 h after appropriate nil per os (NPO) period. Elective = Endoscopy after appropriate NPO period at next available
time
–– Symptomatic patients require intervention

–– Asymptomatic patients can be observed
for 12–24 h
–– Once in the stomach, coins usually pass
without intervention (Fig. 22.2)
–– Can be monitored by checking the stool for
passage and with weekly radiographs, if
indicated
–– If the coin does not pass through the stom-
ach by 4 weeks or if the patient is symp-
tomatic, removal by endoscopy should be
considered
• Button battery in esophagus is an emergency
–– Tissue injury can occur within 2 h of inges-
tion. Remove endoscopically immediately
• Button battery in the stomach
–– Button batteries that are larger than 2 cm in
diameter, are causing symptoms, or are
present for more than 48 h should be Fig. 22.2 Radiograph showing a coin in stomach. It passed
without intervention within 72 h
removed endoscopically
–– If they pass into the duodenum, most pass E sophageal Atresia

in fewer than 72 h and do not require addi- and Tracheoesophageal Fistula (TEF)
tional intervention
• Multiple high strength magnets pose a risk of • Common: 1 in 4000 live births
tissue necrosis in intestines • Five types:
–– Remove before they enter the small bowel –– Esophageal atresia with distal tracheo-
• Food impaction usually associated with esophageal fistula (most common, 86%)
esophageal dysmotility –– Isolated esophageal atresia (8%)
–– Eosinophilic esophagitis –– H-type tracheoesophageal fistula (4%)
–– Esophageal atresia with proximal and dis-
tal tracheoesophageal fistulas (1%)
Reflux Esophagitis –– Esophageal atresia with proximal tracheo-
esophageal fistula (1%)
• Chronic, recurrent epigastric pain, heartburn
• Associated anomalies
(in adolescents), regurgitation, belching, vom-
–– VACTERL: Vertebral, anorectal, cardiac,
iting; brought on by eating, especially acid food
tracheal, esophageal, renal, and limb
• Chronic cough and wheezing
anomalies
• Inflammation of esophagus and lower esoph-
–– Trisomy 13, 18, and 21
ageal sphincter causing dysfunction of LES
–– CHARGE syndrome: Coloboma, choanal
• Empiric treatment with lifestyle changes:
atresia, decreased smell, swallowing and
Small frequent meals, avoid acid foods, avoid
feeding difficulties, hearing loss and bal-
foods that induce reflux (caffeine, chocolate,
ance problems
carbonated beverages), elevate the head of
–– Schisis association: Neural tube defect,
bed
cleft lip/palate, omphalocele, and dia-
• Empiric treatment with acid suppression
phragmatic hernia
• Diagnosis by upper endoscopy with biopsies—
• Survival and prognosis often dependent on
differentiate from eosinophilic esophagitis
associated anomalies
Esophageal Stenosis
PEPTIC ULCER DISEASES
• 3 types: Webs (thin), fibromuscular (thicker),
cartilaginous (distal, more extensive) Acid-peptic disorder refers to acid-related disease
• Frequently presents at 6 months of age when of the esophagus, stomach, and duodenum
solid foods introduced
• Consider achalasia and gastroesophageal
reflux disease Gastritis and Peptic Ulcers
• Can be associated with other anomalies:
Tracheoesophageal fistula, cardiac defects, Peptic ulcers are rare in children, but can be
intestinal atresias, chromosomal abnormalities encountered in extreme cases
772 R. D. Baker
Causes –– PPI+amoxicillin+clarithromycin
• The common causes of peptic ulcers include –– PPI+amoxicillin for 5 days then
H. pylori PPI+clarithromycin +metronidazole for
• NSAIDs, e.g., ibuprofen 5 days
• Stress-related gastric injury –– Other treatment regimens depending on
• Less common causes include ingestion of resistance and treatment failure
corrosive substances, hypersecretory states
(Zollinger-Ellison syndrome), IBD, systemic
mastocytosis, chronic renal failure, and Duodenitis
hyperparathyroidism
• Chronic abdominal pain, nausea, vomiting
Clinical presentation • Causes similar to gastritis, plus celiac dis-
• Poor growth indicates the presence of chronic ease, Crohn’s disease
disease or poor nutrition • Treatment: H. pylori eradication, empiric
• There are no focal findings specific for acid acid suppression, NSAID avoidance, lifestyle
peptic disease changes. Gluten-free diet for celiac disease,
• Dental caries and eroded enamel may indi- immune suppression for Crohn’s disease
cate frequent vomiting or reflux • Diagnosis by upper endoscopy with biopsies
• Pale conjunctiva, tachycardia, or flow mur-
mur may indicate anemia associated with
chronic disease or blood loss Zollinger-Ellison Syndrome (ZES)
• Halitosis with regurgitation or dysphagia may (Rare)
indicate achalasia
• Epigastric tenderness • Caused by gastrin-secreting tumor
• Wheezing or bronchospasm can be associ- • Usually in pancreas, but can be in other areas
ated with chronic reflux • Very high serum gastrin levels
Diagnosis Presentation
• Upper endoscopy with biopsies • Multiple ulcers, usually in the stomach, but
• “Test and treat” strategy for pediatric H. other GI locations
pylori infection is not recommended • Diarrhea, weight loss, GI bleed
• Testing for H. pylori should be performed in
children with gastric or duodenal ulcers. If H. Treatment
pylori infection is identified, then treatment • High-dose proton pump inhibitor
should be advised, and eradication be • Surgical resection if possible
confirmed
• Wait at least 2 weeks after stopping proton
pump inhibitor and 4 weeks after stopping
GASTROINTESTINAL ATRESIA,
antibiotics before testing for H. pylori STENOSIS, AND OBSTRUCTION
Treatment Atresia is congenital absence or closure of tubular
• H. pylori eradication, empiric acid suppres- structure. Obstruction is “luminal discontinuity”
sion, NSAID avoidance, lifestyle changes of any portion of the GI tract. Stenosis is partial
• H. pylori eradication: obstruction.
I nfantile Hypertrophic Pyloric uperior Mesenteric Artery

S
Stenosis (HPS) Syndrome (Cast Syndrome)
(Wilkie Syndrome)
Background
• Male to female ratio 4:1 • Partial to complete obstruction of the duode-
• 3–12 weeks of age, more common in num where it passes between the superior
firstborn mesenteric artery (SMA) and the aorta
• Hypertrophy of the pyloric sphincter muscle –– Aortic-SMA angle is < 25°
causing progressively increasing gastric out- –– Seen in the contexts of severe weight loss,
let obstruction anorexia, surgery (especially surgery for
• Early exposure to erythromycin has been scoliosis)
linked to increase in HPS
Clinical presentation Symptoms—vomiting, gastric distention

• Visible peristalsis, palpable pyloric mass Treatment—condition resolves with weight gain
(“olive”), hungry, dehydrated, decreased • Eat in supine position
urination • Enteral tube feeding if possible
• Non-bilious, projectile vomiting containing • TPN
HCL
• Hypochloremic, hypokalemic metabolic
alkalosis Duodenal Atresia
• Carbon dioxide retention
• 1 in 6000 live births in the USA. Two-thirds
Diagnosis—suggestive symptoms and physical thought to be due to failure of recanaliza-
exam tion, while the remainder due to annular
• Ultrasound is definitive—pyloric muscle wall pancreas, pre-duodenal portal vein, Ladd’s
should be less than 3 mm bands
• Ultrasound diagnostic criteria for pyloric • Associated anomalies: Down syndrome, mal-
stenosis: rotation, congenital heart disease
–– Pyloric thickness > 4 mm • Outcome frequently depends on associated
–– Pyloric length > 14 mm abnormalities
• Upper GI series—classic “string” sign. Can • Prenatal ultrasound shows polyhydramnios
look for other causes of obstruction 30–60% of the time. Sometimes fluid-filled
fetal stomach and proximal duodenum
Treatment • Postnatal vomiting usually bilious, but not
• Stabilize—evacuate stomach, IV fluid resus- always
citation, correct electrolytes • No abdominal distension
• Surgery—pyloromyotomy. Atropine works • “Double bubble” on radiograph because of
but hospital stay prolonged stomach distension and proximal small bowel
distension. Gasless distal GI tract
Adrenal insufficiency can present like HPS • Correction is planned surgery—stabilization,
• But hyponatremia, hyperkalemic acidosis, empty stomach, and proximal duodenum;
and hypotension
774 R. D. Baker
look for complicating features. During sur- • Definition for children 4 or older same as
gery check for additional GI atresias before but must exclude IBS
• Constipation is very common, as many as
40% of all children
Jejunal Atresia
Constipation and withholding
Animal models show that vascular incidents that • When a child does not recognize or respond
cause ischemia result in necrosis and subsequent to the urge to defecate, stool is retained in the
atresia rectum, the urge to defecate subsides, and the
rectal wall stretches to accommodate the fecal
Atresia types load
• Type I: Intraluminal web with continuity of • Repeated withholding or avoidance of defe-
muscular layers cation leads to larger stool load in the rectum,
• Type II: Complete atresia with fibrous cord causing further stretching and potential thin-
connecting segments ning of the rectal wall
• Type IIIa: Complete atresia with V-shaped • The retained stool becomes larger, harder,
defect in the associated mesentery drier, and more difficult to pass the next time
• Type IIIb: Extensive mesenteric defect with the urge arises
distal small bowel spiraling around vascula-
ture forming “apple-peel” Clinical presentation
• Type IV: Multiple atresias along a segment • Abdominal pain (pain can be severe enough
of bowel to mimic an acute abdomen)
• Usually atresias are accompanied by “micro- • Rectal bleeding and anal fissure
colon,” but this finding is nonspecific • Abdominal distension, tenderness to palpa-
tion, and presence of fecal mass
• External anal inspection can assess for anal
Colonic Atresias atresia and displacement and may identify
anal fissures, skin tags, or external hemor-
• Follow similar pattern but must be clearly rhoids. Digital rectal examination (DRE) is
distinguished from Hirschsprung disease not always necessary to make the diagnosis in
classic cases
–– Palpation of a firm or large rectal stool
FUNCTIONAL CONSTIPATION mass on rectal examination often confirms
(ROME IV, H3A) clinical suspicions; abnormalities in
sphincteric tone may indicate anal
Definition stenosis
• Must have at least 2 of the following: –– Empty rectal vault with expulsion of stool
–– Less than 2 defecations per week on finger withdrawal is a classic but infre-
–– At least one accident per week after toilet quently seen finding in Hirschsprung
training is complete disease
–– History of stool retention
–– Painful bowel movements Abdominal radiograph (KUB)
–– Fecal mass in rectum • Abdominal radiograph is not required to
–– Large diameter stool—obstruct the toilet make the diagnosis in classic cases of func-
–– Other symptoms: Irritable, decreased tional constipation
appetite
onfunctional Causes of
N
Constipation (Compared to functional
constipation, these are much less
common)
• Anatomic
–– Imperforate anus
–– Anal stenosis
–– Abnormal musculature, prune belly, gas-
troschisis, Down syndrome
• Dysmotility
–– Hirschsprung disease
–– Hypothyroidism (hypopituitarism)
–– Diabetes mellitus
–– Colonic inertia
–– Anal achalasia
–– Visceral myopathies
• Drug-, toxin-induced
–– Heavy metals (lead)
–– Opiates
–– Chemotherapy
–– Antidepressants
Fig. 22.3 5-year-old with encopresis for 2 years and fecal –– Vitamin D intoxication
impaction. The radiograph shows large amount of stool in • Associated with other diseases
colon and rectum –– Celiac disease
–– Cystic fibrosis
• Fecal burden and impaction usually seen on –– Multiple endocrine neoplasia 2B
KUB (Fig. 22.3) • Spinal cord anomalies
–– Tethered cord
Treatment
–– Trauma
• Demystification—explain what is happening
and why
–– Incontinence is “constipation with over- E ncopresis
flow” and is involuntary
–– Younger child likely to “withhold” rather • Encopresis is the repeated passage of feces
than “attempt to expel” into inappropriate places (usually the
• Cleanout underpants)
–– High-dose osmotic laxatives to rid the • It is also called fecal incontinence
colon of formed stool, e.g., polyethylene
glycol (PEG 3350), lactulose, and magne- Pathophysiology
sium products such as magnesium hydrox- • Prolonged and repetitive stool withholding
ide and magnesium citrate and avoidance of defecation lead to large
–– Daily dose osmotic laxative to maintain amounts of retained stool in the rectum
regular defecations • The large fecal mass becomes impacted and
–– Toilet sitting to establish bowel habits extremely difficult to evacuate. Peristaltic
–– Maintaining adequate hydration is a safe movement of the colon pushes semiformed
recommendation and liquid stool lower in the colon, resulting
776 R. D. Baker
in leakage around the large mass of stool into Cause

the child’s underpants • RET proto-oncogene considered the major
cause of HD
Management
• Disimpaction with osmotic laxatives Associations
• Maintenance therapy with osmotic laxative • Trisomy 21
on daily basis • Waardenburg-Shah syndrome
• Behavioral modification • Ondine’s curse—congenital central hypoven-
• Education tilation syndrome
• Multiple endocrine neoplasia
• Neurofibromatosis
Anal Fissure • Neuroblastoma
• Split in the squamous epithelium distal to the Diagnosis (Table 22.9)

dentate line (mucocutaneous junction) • Early constipation—no passage of meconium
• Acute fissure—blood on the surface of the within 24 h of birth is suggestive
stool, toilet paper, or dripping from the anus • Deep rectal biopsy
–– Usually caused by constipation • Un-prepped contrast enema
–– Treatment—osmotic laxatives and sitz • Motility only in older child—cooperation
baths required
–– If not in midline or difficult to heal, think
of underlying disease Treatment
◦◦ Immune deficiency • Surgical excision of aganglionic segment
◦◦ Crohn’s disease with reconstruction using normal proximal
• Chronic anal fissure—indurated edges, not bowel results in satisfactory function in the
always in midline majority of cases
–– Immune deficiency, Crohn’s disease
–– Trauma Hirschsprung Disease-Associated Enterocolitis
–– Infection—venereal disease, skin • Severe diarrheal illness
tuberculosis • Probably infectious
–– May still be merely chronic constipation • Can occur even after correction
–– Treatment—stool softeners, sitz baths; • Less common after 2 years of age
treat any underlying condition
Hirschsprung Disease (HD) Table 22.9 Differences between functional constipation

and Hirschsprung disease
• Aganglionosis of rectum and distal sigmoid
Functional constipation Hirschsprung disease
but can include varying lengths of the colon Passage of meconium in Delayed passage of meconium
and rarely the entire GI tract (total intestinal the first 24 h > 24 h
aganglionosis) Full rectal vault Empty rectal vault
• Failure of the neural crest cells to populate Large stool caliber Pencil-thin stool
Normal ganglion cells Absent ganglion cells in the
the myenteric plexus
in the myenteric and myenteric and submucosal
• Never any skip areas; extends from rectum submucosal plexus plexus of rectum and distal
caudad sigmoid
• 1 in 5000 live births; 4:1 male to female ratio Encopresis may be Not associated with encopresis
present
INFLAMMATORY BOWEL
DISEASE (IBD)
Chronic unchecked inflammation
• Genetic component
• Immune and microbial components
• Involves the GI tract but extraintestinal mani-
festations are common
• Incidence peaks between 15 and 30 years of age
–– Very-early-onset IBD (VEOIBD) less than
5 years may have uncommon immune defi-
ciency—refer to immunologist
Histologic features of IBD (Fig. 22.5)

Fig. 22.4 A toddler with rectal prolapse due to chronic
Ulcerative Colitis (UC)
constipation • Affects the colon
• Inflammation of the mucosal layer
Rectal Prolapse • No skip areas from distal colon (usually
spares rectum) to ileocecal valve (sometimes
Protrusion of one or more layers or the rectum
“backwash” ileitis found)
(Fig. 22.4)
Crohn’s Disease (CD)
• Common in children less than 4 years
• CD includes Crohn’s enteritis and Crohn’s
• Predisposing factors
colitis
–– Straining with constipation or toilet
• Can involve any portion of the GI tract from
training
oral cavity to anus
–– Diarrhea
• Transmural inflammation can lead to perfora-
–– Intestinal parasites—check stool for ova
tion and/or abscess formation
and parasites
• Can affect nutritional status and growth
–– Malnutrition with muscle wasting
–– Cystic fibrosis—test for CF Indeterminate Colitis (ID)
• Unusual causes • Features do not clearly categorize it as CD or
–– Juvenile polyps UC
–– Solitary rectal ulcer • Most cases will eventually be recognized as CD
–– Ehlers-Danlos syndrome
• Procidential—prolapse of all layers Crohn’s disease compared to features of ulcer-
–– Usually requires manual reduction ative colitis (Table 22.10)
Diagnosis of IBD
Treatment • Index of suspicion
• Usually self-resolving –– Teenager with chronic abdominal pain, diar-
• Avoid straining—supported toilet sitting rhea, blood in stool, unexplained anemia,
• Stool softeners if indicated weight loss or poor weight gain, retarded
• Injection sclerotherapy and rectopexy are last growth, retarded pubertal development
resorts –– Family history of IBD
778 R. D. Baker
Fig. 22.5 Histologic
features of inflammatory
bowel disease showing
crypt atrophy and basal
plasmacytosis
Table 22.10 Distinguishing features of Crohn’s disease Screening studies:

and ulcerative colitis • CBC differential, platelet count
Crohn’s • ESR, CRP, stool calprotectin
Feature disease Ulcerative colitis • Chemistries including total protein and
Serositis + −
albumin
Thickened bowel wall + −
Except with • Stool for occult blood and stool cultures
carcinoma • Serologic tests: Anti-Saccharomyces cerevi-
Stricture + − siae antibodies (ASCA), outer membrane
Except with protein C (OmpC) for CD, perinuclear anti-
carcinoma neutrophil cytoplasmic antibodies (pANCA)
Mucosal edema + −
(Usually)
for UC, and others (use only as adjunctive
Ulcers + + information)
(In one line) • Imaging: Abdominal radiograph, upper GI
Fat wrapping + − series with small bowel follow-through, CT
Fistula + − of abdomen with IV and PO contrast, and
Distribution Focal Diffuse
MRI with IV and PO contrast (MRE); upper
Rectal involvement − +
Granuloma + −
GI and barium enema largely replaced by
Fissuring ulcers + − more advanced imaging
Transmural + −
inflammation Definitive diagnosis
Submucosal edema + − • Colonoscopy with terminal ileal intubation
Submucosal + − • Simultaneous upper endoscopy adds infor-
inflammation
mation even if negative
Neuronal hyperplasia + −
Thick muscularis + + • If suspicion is high and esophagogastroduo-
mucosa (Patchy) (Diffuse) denoscopy (EGD) and colon are negative,
Pyloric gland + − consider capsule endoscopy or double bal-
metaplasia loon endoscopy
Mucosal inflammation + +
(Focal) (Diffuse)
Treatment of IBD
Architectural + +
distortion (Focal) (Diffuse) • Initially UC, CD, and ID treated similarly
Paneth cell metaplasia − + with immune suppression
(Usually, no) –– Steroids to induce remission, then wean
–– Immunomodulators: 6-mercaptopurine and • Chronic constipation (paradoxical)

methotrexate • Recurrent abdominal pain
–– Biologics: Infliximab, adalimumab, and • Vomiting
others • Short stature
–– CD can be initially treated with enteral • Pubertal delay
nutrition • Iron deficiency
–– Surgery • Dermatitis herpetiformis rash
–– In severe UC, colectomy with J-pouch is • Abnormal liver tests
an option • Chronic fatigue
–– In CD abscesses, strictures, perforation
may require surgery At-risk individuals
• First-degree relatives
• Autoimmune thyroiditis
Gluten-Sensitive Enteropathy • Type 1 diabetes
• Down syndrome
(Celiac Disease) • IgA deficiency
• Inflammatory disease of small intestine • Turner syndrome
• Immune regulated • Williams syndrome
• Sensitivity to dietary gluten • Juvenile chronic arthritis
• Genetic predisposition required—HLA-DQ2/
Serologic screening tests done on a gluten-con-
DQ8 required
taining diet (at least 3 g/day for 6 weeks)
• Occurs in 1 in 100 to 1 in 200 individuals in
• Tissue transglutaminase (tTG)
general population
–– tTG-IgA is highly sensitive and specific
• Grains containing gluten:
and cost- effective, less sensitive under
–– Wheat, barley, and rye
2 years of age
–– Oats do not contain gluten, but may be
–– tTG-IgG not as sensitive or specific, but
contaminated during processing
useful in IgA deficient individuals
–– Buckwheat is gluten-free
• Anti-endomysial antibody (EMA)—as good
Signs and symptoms (otherwise not explained) as tTG-IgA but more expensive and operator
• Failure to thrive dependent
• Persistent diarrhea • Deamidated gliadin peptide (DGP)—useful
in young children less than 2 years of age
Fig. 22.6 Histologic
features of celiac disease
with marked villous
blunting and crypt
hyperplasia, an increase
in intraepithelial
lymphocytes
780 R. D. Baker
Definitive diagnosis • Decreased enzyme and bicarbonate

• Upper endoscopy with small bowel and stom- production
ach biopsies recommended –– Fat and fat-soluble vitamin malabsorption
–– Lifelong, life-altering diagnosis dictates –– Decreased enzyme activation
maximum certainty
–– Staging—Marsh classification Diagnosis of PI
• Stimulation of the pancreas with IV secretin/
Histologic features of celiac disease (Fig. 22.6) cholecystokinin and collection of pancreatic
Treatment and outcomes secretion via duodenal tube (endoscope) is
• Lifelong gluten-free diet most accurate way of assessing function but
–– Resolution of symptoms in most individuals infrequently done because of invasive nature
–– Serologic markers normalize usually of test
within weeks but can be up to a year • 72-hour fecal fat collection—amount of fat in
–– Small bowel mucosa returns to normal stool is compared to amount of fat in diet,
–– Risk of GI neoplasm reduced, but not to 85% absorption in infants, 93% in older chil-
baseline dren and adults—not often done because
• Long-term (yearly) follow-up recommended laborious and unpleasant
–– Dietary adherence • Test of choice: Fecal elastase measures pan-
–– Growth and development creatic elastase in stool—not affected by
–– Bone health exogenously administered enzymes but can-
not be used to assess adequacy of enzyme
replacement
Cystic Fibrosis (CF)
Pancreatic enzyme replacement
GI/Hepatobiliary Manifestations • Exogenous enzymes administered with all
• Caused by mutation in cystic fibrosis trans- meals and snacks
membrane conductance regulator protein • Fat-soluble vitamins need to be monitored
(CFTR) and supplemented
• Over 2000 mutations listed in database—
F508del is the most common CF-Related Diabetes Mellitus (CFRD)
• Mutation causes abnormally tenacious mucus • As damage progresses to pancreatic tissue,
and secretions affecting lungs, pancreas, hep- there is a decrease in:
atobiliary tract, GI tract, and sweat glands –– Glucagon-producing alpha cells
–– Insulin-producing beta cells
Diagnosis of CF most often with newborn screen • Prevalence increases with age, 75% overall,
(available in all 50 states in the USA) 50% of adults, 20% of adolescents
• Measures immunoreactive trypsinogen (IRT) • Occurs only in pancreatic insufficient (PI)
but must be confirmed by sweat test or gene individuals
testing –– Worsening lung function and nutritional sta-
tus associated with development of CFRD
Pancreatic Insufficiency (PI)
• Occurs in approximately 85% of CF patients Pancreatitis
and is somewhat gene mutation specific • 20% of pancreatic sufficient (PS) CF individ-
• Prevalence increases with age uals will experience bouts of pancreatitis
• Treatment is IV fluids, enteral nutrition, anal- • Esophageal varices and bleeding

gesia, plus/minus enzymes • Liver failure requiring transplantation
• Repeated bouts can lead to pancreatic
“burnout” Treatment
• Avoid liver toxic medications and substances
Gastrointestinal Issues • Immunize against hepatitis A and B
• Decreased motility due to decrease in GI • Optimize nutrition
secretions and thick mucus layer • Plus/minus ursodeoxycholic acid (CF
• Meconium ileus Foundation recommends its use; others have
–– Partial or complete obstruction at birth suggested that it is not helpful)
–– Relieved by hyperosmolar enemas 50–90% • Treat esophageal varices with endoscopic
of the time banding
–– Sometimes complicated by perforation, • Liver transplant when necessary
peritonitis, volvulus, atresia
–– Surgery
• Distal intestinal obstruction syndrome (DIOS) Shwachman-Diamond Syndrome
(previously called meconium ileus equiva- (SDS)
lent)—impaction of fecal material at distal
ileum, cecum, and proximal colon Characteristics
–– Occurs at any age • Pancreatic insufficiency
–– Most often treated with polyethylene gly- –– Fatty infiltration of pancreas affecting aci-
col lavage nar cells; requires enzyme replacement
–– N-Acetylcysteine enemas rarely used –– Can be visualized on CT
because of success with lavage –– Improves with age—some no longer
• Nutrition—intake frequently inadequate in CF requiring enzyme replacement
–– Increased work of breathing • Bone marrow dysfunction
–– Decreased appetite –– Persistent neutropenia—frequent infec-
–– Residual malabsorption tions requiring prophylactic antibiotics;
–– Good nutrition without fat restriction human granulocyte stimulating factor—
important, but obesity should be avoided bone marrow transplant
–– Dietary advice should be individualized –– Red cells and platelets may be affected
• Rectal prolapse • Skeletal abnormalities 50% of individuals
–– Long-bone dysostosis
Hepatobiliary Complications –– Metaphyseal chondrodysplasia
• Virtually all CF patients will have some liver –– Thoracic cage abnormalities 30% of
diseases individuals
–– Prevalence increases with age, 20% of adults
have clinically significant liver disease
Pancreatic Insufficiency Differential
Manifestations Diagnosis
• Neonatal cholestasis
• Hepatomegaly • Cystic fibrosis
• Raised levels of liver enzymes • Shwachman-Diamond syndrome
• Hepatic steatosis • Johanson-Blizzard syndrome
• Focal biliary cirrhosis –– Deafness
• Multilobular cirrhosis with portal hypertension –– Imperforate anus
782 R. D. Baker
–– Urogenital malformations • Child’s small intestine 200–250 cm, adult’s

–– Dental anomalies 300–800 cm
• Pearson syndrome • Infant with 15 cm small bowel with ileocecal
–– Refractory sideroblastic anemia valve of 20 cm or more without ileocecal
• Jeune syndrome valve can eventually wean from TPN
–– Anomalies of upper thoracic bones leading • Trophic feeds will increase pancreatobiliary
to respiratory compromise flow and decrease TPN toxicity
Long-term complications of short bowel

Primary Intestinal Lymphangiectasia • Renal stones secondary to steatorrhea Ca,
binds to fat and not to oxalate, excess oxa-
Background lates reabsorbed, and excreted in urine
• Obstruction of lymphatic drainage of the • Bloody diarrhea secondary colitis as a result
intestine of enteral feeding (this may improve with
• Diffused or local dilation of enteric hypoallergenic diet)
lymphatics • Constipation
–– Leads to protein-losing enteropathy • Failure to thrive
Associated condition
• Turner syndrome
Bacterial Overgrowth Syndrome
• Noonan syndrome
• Klippel-Trenaunay syndrome Background
• Weber syndrome • Overgrowth of aerobic and anaerobic bacteria
• Heart failure in the small bowel
• The normal small intestine has relatively few
bacteria residing inside
• Varies in severity from asymptomatic to
life-threatening Mechanism of development of diarrhea
• Protein-losing enteropathy is the main cause • Bile acids are deconjugated and fatty acids
of the clinical manifestations of this disease hydroxylated by bacteria
• These processes lead to an osmotic diarrhea
Diagnosis
• Presence of alpha-1 antitrypsin in stool Conditions may result in bacterial overgrowth
• Direct measurement of alpha-1 antitrypsin • Short bowel syndrome
clearance from plasma • Pseudo-obstruction
• Bowel strictures
Management
• Malnutrition
• Replace long-chain fat with medium-chain
• Previous GI surgery
triglycerides in diet or formula and treatment
of the cause Clinical presentation
• Diarrhea
• Bloating
Short Bowel Syndrome • Abdominal distension
• Abdominal pain or discomfort
Background
• Fatigue
• Loss > 50% of small intestine with or without
• Weakness or lethargy
portion of large intestine can result in gener-
• Ataxia
alized malabsorption
Diagnosis Management of acute diarrhea with dehydration

• History • Oral or nasogastric hydration with oral rehy-
• Breath hydrogen with lactulose testing dration solution (ORS) for mild to moderate
• Neurologic findings dehydration
• Metabolic acidosis (low HCO3) • Regular diet
• Elevated D-lactic acid • Avoid juices and soft drinks, e.g., apple juice,
Sprite, 7-Up, or Gatorade
Treatment complications • Fluid therapy for a patient with acute gastro-
• Malabsorption enteritis unresponsive to oral rehydration
• Fat-soluble vitamin loss • Several advances in formulation of ORS have
improved efficacy
Therapy • Oral hydration technique:
• Broad-spectrum antibiotics cover Gram- –– Patients with mild to moderate dehydration
negative and anaerobic bacteria, e.g., metro- should receive 50–100 mL/kg of ORS over
nidazole or with nonabsorbable rifaximin 2–4 h to correct fluid deficit
–– In addition, ongoing fluid losses from vom-
Surgical management
iting or diarrhea should be replaced
• Depends upon the underlying cause
–– For children with significant vomiting,
ORS should initially be administered in
5-mL aliquots every 1–2 min
DIARRHEA –– Administration of fluid with a teaspoon,
• Usually self-limited; recovery in a few days syringe, or dropper may facilitate initial
• Most children with or without dehydration fluid resuscitation
can continue to eat – – Fluid volumes can be increased as
• Reason for diarrhea tolerated
–– Viral –– Repletion for ongoing fluid losses may be
–– Bacterial estimated at 5–10 mL/kg (5 mL/kg for each
–– Parasitic emesis and 10 mL/kg for each diarrheal
–– Antibiotic associated episode)
–– Osmotic • Between 5% and 15% of children with acute
–– Inflammation diarrhea continue to be have clinical signs of
–– Starvation dehydration 4 h after starting ORS
–– Fluid treatment for severe dehydration
Clinical presentation –– Nasogastric, nasojejunal, intravenous,
• Diarrhea, non-blood or bloody intraosseous fluids
• Nausea and vomiting may be present –– ORS, normal saline, lactated Ringer’s
• Dehydration symptoms: solution
–– Increased thirst, irritability, or lethargy –– Normal saline and albumin boluses have
–– Dry or parched mucous membrane worse outcome than no-bolus therapy
–– Sunken fontanel
–– Reduced skin turgor
Important tips for management of diarrhea
–– Prolonged capillary refill
• Vitamin A deficiency increases the risk of
–– Reduced urine output
dying from diarrhea, measles, malaria by
–– Tachycardia, normal or low blood pressure
10–24%
784 R. D. Baker
• Zinc deficiency increases the risk of mortality –– If no response, the second line is vancomy-
from diarrhea, pneumonia, and malaria cin (oral)
• Persistent diarrhea lasts at least 14 days; nutri- • Entameba histolytica
tional supplementation is very important –– Metronidazole followed by iodoquinol or
• Ondansetron is an effective and less toxic paromomycin
antiemetic (if diarrhea associated with persis- • Campylobacter jejuni
tent vomiting) and may limit dehydration and –– Erythromycin or azithromycin
hospitalizations
Extraintestinal manifestations and clues to Chronic Diarrhea

causative agent
• Reactive arthritis: Salmonella, Shigella, • Malabsorptive
Yersinia, Campylobacter, Cryptosporidium, –– Carbohydrate—see “Disaccharide
Clostridium difficile Intolerance”
• Guillain-Barré syndrome: Campylobacter –– Toddler’s diarrhea—chronic diarrhea of
• Glomerulonephritis: Shigella, Campylobacter, unknown etiology in a toddler who is oth-
Yersinia erwise doing well
• Appendicitis-like presentation: Yersinia ◦◦ Thought to be due to excessive fructose/
• IgA nephropathy: Campylobacter sorbitol
• Erythema nodosum: Yersinia, Campylobacter, ◦◦ Treatment—eliminate juice but main-
Salmonella tain normal diet
• Hemolytic uremic syndrome (HUS): Shigella –– Fat malabsorption—greasy, bulky, foul-
dysenteriae 1, E. coli O157: H7 smelling stool
• Hemolytic anemia: Campylobacter, Yersinia ◦◦ Diagnosis—72-h fecal fat collection with
calculation of percent fat absorption
Antibiotics and drug of choice in treatment of ◦◦ Cholestasis—biliary atresia, primary
diarrhea sclerosing cholangitis
• Most cases of diarrhea are self-limited, and ◦◦ Pancreatic insufficiency
no antibiotic treatment is needed, and in some ◦◦ Bile salt malabsorption—ileal disease
cases, antibiotics are contraindicated and/or resection
• Shigella • Postinfectious enteritis—in minority of cases
–– Ciprofloxacin, trimethoprim-sulfamethox- of infectious diarrhea, persistent mucosal
azole, and azithromycin damage leads to persistent diarrhea
–– Third-generation cephalosporin is appro- –– Mechanism is not understood but is not
priate empiric therapy in the setting of disaccharidase deficiency
acute illness –– Postinfectious enteritis has become much
• Salmonella less common since recommendations to
–– Antibiotics are indicated in infants “feed through” diarrhea have been
< 3 months, patients with systemic dis- implemented
eases, malignancy, or
immunocompromised Chronic Inflammatory Diarrhea
–– Third-generation cephalosporin, e.g., • Collagenous colitis (microscopic colitis)
cefotaxime –– Submucosal collagenous bands on colonic
• C. difficile biopsy
–– Metronidazole oral or IV is the first line, –– Lymphocytic/eosinophilic infiltrates on
may use again if relapse; this just means colonic biopsy
reinfection and is not a resistance –– Oral budesonide may induce remission
• Eosinophilic gastroenteritis Table 22.11 Difference between congenital chloride and

–– Dense infiltrate of eosinophils in intesti- sodium diarrhea
nal biopsy, with or without peripheral Type of congenital secretory
eosinophilia diarrhea Clinical features
Congenital chloride diarrhea Low PH diarrhea (acid)
–– Diagnosis of exclusion—all other reasons
Metabolic alkalosis
for intestinal eosinophilia must be ruled out Cl–/HCO3– transport defect Hypochloremia
• Allergic colitis (protein-induced colitis) High chloride in stool
–– Non-IgE allergy to food protein (com- Congenital sodium diarrhea High pH diarrhea
monly cow protein and/or soy protein in (alkaline)
Metabolic acidosis
formula or breast milk) induces proctitis Na+/H+ transport defect Hyponatremia
–– Streaks of blood and mucus in stool High Na in stool
–– Usually responds to hypoallergenic for-
mula or mother’s elimination diet
–– Resolves by 12–18 months of age opathy, X-linked) syndrome and mutation
• Food protein-induced enterocolitis syndrome in FOXP3 gene
(FPIES)—uncommon • Congenital chloride diarrhea—defect in Cl–/
–– Vomiting HCO3– exchanger in the intestine (Table 22.11)
–– Non-bloody diarrhea –– Stool chloride exceeds stool Na+ plus K+
–– Failure to thrive when hydrated
• Celiac disease – – May be history of polyhydramnios and/or
• IBD dilated loops of fetal intestine
–– Treatment—replace chloride and maintain
VIPoma hydration
• Watery diarrhea—hypokalemia—acidosis • Congenital sodium diarrhea—rare defect in
syndrome Na+/H+ exchanger
• Excessive secretion of vasoactive intestinal –– Decrease Na+ absorption and increased
peptide (VIP) stool Na+
–– Metabolic acidosis and hyponatremia
Congenital Diarrhea –– Replace Na+ and maintain hydration
• Microvillus inclusion disease—rare severe
secretory diarrhea starting from neonatal
period to a few months of age Disaccharide Intolerance
–– Myosin motor protein type Vb mutation in
Lactose intolerance
some families
• Primary alactasia—rare congenital, complete
–– Severe dehydration and metabolic acidosis
lack of lactase enzyme
require IV/oral correction
• Primary hypolactasia—common genetic lack
• Tufting enteropathy—presents similarly to
of lactase persistence allele, associated with
microvillus inclusion disease
decreased lactase with age
–– “Tufts” of epithelial membrane partly sep-
–– The amount of lactose that can be tolerated
arated from villus tip
is extremely variable from one individual
–– Variable villus atrophy
to another and is not entirely based on the
• Autoimmune enteropathy—diarrhea in early
activity of the residual lactase
infancy
–– Lack of lactase persistence allele has geo-
–– Villus atrophy, crypt hyperplasia, inflam-
graphic and ethnic variability
matory infiltrate
• Secondary hypolactasia—temporary decrease
–– Can be associated with IPEX (immune
in lactase due to intestinal injury, severe gastro-
dysregulation, polyendocrinopathy, enter-
enteritis, celiac disease, Crohn’s disease, etc.
786 R. D. Baker
Management of lactose intolerance, taking into • Red blood: Upper stomach, esophagus, extra-
consideration the mechanisms causing the GI, or brisk bleed
disorder • Esophageal erosion
• Primary alactasia—lifelong avoidance of • Mallory-Weiss gastropathy
milk and dairy products. Use of Lactaid –– Forceful vomiting/retching forces cardia of
treated products can be attempted stomach through diaphragmatic opening,
• Primary hypolactasia—small to moderate resulting in tearing of mucosa
amounts of lactose-containing foods may be –– Treat the cause of vomiting—short course
tolerated. Lactase-treated products may be used of acid suppression
• Secondary hypolactasia—if lactose intoler- • Gastritis
ance is due to acute infectious gastroenteritis, –– H. pylori—triple therapy—2 antibiotics
no treatment may be required or decrease and acid suppression
dairy products for a short time. If injury is • Ulcer, gastric, and duodenal—most due to H.
more long-lasting (celiac disease, Crohn’s pylori infections
disease) low-lactose diet combined with –– Cobblestone appearance of antral mucosa
lactase-treated dairy may be required. When on endoscopy
gastrointestinal injury has resolved, dairy • Extra-GI
products can be resumed –– Nosebleed
–– Hemoptysis
• Esophageal varices
GASTROINTESTINAL BLEEDING
Esophageal Varices
• Occult bleeding—detected by testing for
blood in stool Background
–– Source can be upper/lower GI tract or • Cavernous or portal vein thrombosis is the
extra-GI in origin (e.g., nosebleed) most common type
• Melena is black, tarry stool suggestive of • Umbilical vein thrombosis in neonates
bleeding from the proximal GI tract
–– Black stool can be due to medication and Causes
foods—test for blood • Portal hypertension
• Hematochezia bright red blood per rectum • Mediastinal tumor
suggestive of lower GI bleed or very brisk • Superior vena cava (SVC) thrombosis
upper GI bleed • Chronic liver disease resulting in portal
• Hematemesis is vomiting blood—can be dark hypertension
(coffee grounds) or red
• Hematemesis
Upper GI Bleeding • Splenomegaly
ematemesis: Check Gastroccult—Is It

H Diagnosis
Really Blood? • Upper endoscopy (Fig. 22.7)
• Suggests bleeding is proximal to ligament of
Management
Treitz
• Treatment of the cause
• Dark/coffee grounds: Has been exposed to
• Band ligation
stomach acid
• Sclerotherapy
–– Coagulopathy
–– Eosinophilic gastroenteritis
–– Very-early-onset IBD
• Preschool
–– Infection colitis
◦◦ Salmonella, Shigella, E. coli, Yersinia,
Campylobacter, C. difficile
–– Hemolytic uremic syndrome—E. coli
O157: H7
–– Henoch-Schönlein purpura—IgA vasculitis
–– Juvenile polyps
–– Solitary rectal ulcer
• School age and adolescent
–– IBD
Fig. 22.7 Endoscopic picture of esophageal varices
(arrows). (Courtesy of Sherif Elhanafi, MD, Department of
Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Meckel Diverticulum
Arizona)
Background
Lower GI Bleeding • Congenital anomaly: Remnant of the yolk sac
that remains attached to the intestine and
• Infant develops lining epithelium similar to that of
–– Swallowed maternal blood—Apt test the stomach
–– Anorectal fissure—examination • Rule of two: 2% of population, 2:1 male to
–– Necrotizing enterocolitis—imaging for female ratio, 2 ft from ileocecal valve, 2 in.
pneumatosis intestinalis long, 2% of individuals develop complica-
–– Malrotation/midgut volvulus imaging, tions, usually before the age of 2
upper GI series • May occur in the first decade of life
–– Hirschsprung-associated enterocolitis— • Ulceration of adjacent ileal mucosa from acid
antibiotics and fluid resuscitation, then un- of ectopic stomach mucosa can cause inter-
prepped contrast enema mittent painless bleeding
–– Coagulopathy (e.g., vitamin K deficiency),
coagulation studies (prothrombin time Clinical presentation
[PT], partial thromboplastin time [PTT)] • Significant painless rectal bleeding is Meckel
and international normalized ratio [INR]. diverticulum until proven otherwise
Gastric or duodenal ulcer with brisk • Stool is brick- or currant jelly-colored, bleed-
bleed—upper endoscopy ing can be less dramatic melanotic stools
–– Duplication cyst—imaging • Anemia and hypovolemia (the bleeding is
• Infant and toddler usually self-limited due to contraction of
–– Anal fissure splanchnic vessels)
–– Milk- or soy-induced colitis—remove sus- • Obstruction because Meckel diverticulum
pected allergens from child’s diet may act as a leading point for
–– Intussusception—ultrasound imaging intussusceptions
–– Meckel diverticulum • Meckel diverticulitis with a presentation sim-
–– Duplication cyst ilar to appendicitis
788 R. D. Baker
Diagnosis
• The most sensitive test is Meckel diverticu-
lum scan, 99m technetium pertechnetate
• The uptake can be enhanced by cimetidine,
glucagon, and gastrin
Treatment
• Surgical
POLYPS
ingle Hamartomatous Polyp
S
(Juvenile Polyp) (Fig. 22.8)
Fig. 22.8 Histologic features of a juvenile polyp showing
• Common spherical, eroded and granular surface, stromal compartment
expanded, low crypt density, and flattened reactive
• 0.5–5.0 cm in diameter epithelium
• Painless, bright red rectal bleeding
• Sometimes seen protruding from rectum or in
diaper after auto-amputation • Indications for genetic testing:
• There can be up to 5 polyps –– Children with 5 or more juvenile polyps
• 70% in rectosigmoid area but can be in proxi- –– Any number of adenomatous intestinal
mal colon polyps
–– No malignant potential
• Should be removed with pan-colonoscopy J uvenile Polyposis Syndrome (JPS)
and polypectomy
–– Rule out polyposis syndrome • Sometimes associated with mutation in
–– Can perform repeat polypectomy SMAD4 gene—presents in 3 forms:
–– Juvenile polyposis of infancy with rectal
prolapse, diarrhea, bleeding, and protein-
Intestinal Polyposis Syndromes losing enteropathy—death before 2 years
despite colectomy
• Multiple hamartomatous polyps with –– Juvenile polyposis coli—only the colon
increased malignant potential involved
• Autosomal dominant –– Generalized juvenile polyposis syndrome
• Includes 4 separate types: occurs throughout the GI tract and can
–– Juvenile polyposis syndrome (JPS) affect nutrition and growth
–– Peutz-Jeghers syndrome (P-JS)
–– Cowden syndrome (CS)—a PTEN Peutz-Jeghers Syndrome (P-JS)
mutation • Rare—autosomal dominant
–– Bannayan-Riley-Ruvalcaba syndrome • Mucocutaneous freckling
(BRRS)—a PTEN mutation
• Hamartomatous polyps throughout the GI tumors in adults, increased risk of extra-GI

tract, mainly small bowel tumors.
• 90% will have mutation in STK11 tumor sup- • Congenital hypertrophy of the retinal pig-
pressor gene ment epithelium (CHRPE) may be a tip-off to
• Start screening for malignancy at 8 years of the diagnosis of FAP
age with capsule endoscopy; if negative, • Surveillance
restart at 18, every 3 years –– Whether familial gene mutation is known
• Midgut polypectomy via laparoscopy, intra- or not, yearly screening starting at age
operative endoscopy, or double balloon 10 years
endoscopy—requires an expert –– When greater than 100 adenomas found or
adenomas greater than 5 mm, perform col-
owden Syndrome (CS): Rarely Presents
C ectomy with ileorectal anastomosis or ileo
in Childhood pouch anal anastomosis
• Small hamartomatous polyps distal to the –– Still need annual sigmoidoscopy
hepatic flexure • Risk of desmoid—increased risk with FAP
• Associated anomalies: Macrocephaly, papil- –– Non-metastasizing, locally expanding
lomatous papules, keratosis tumor of the abdominal wall or within the
abdomen
Bannayan-Riley-Ruvalcaba Syndrome –– No effective treatment
(BRRS) –– Surgery carries high mortality rate
• Polyps mainly in ileum and colon
• Associated anomalies: Macrocephaly, devel-
opmental delays, boney malformation of LIVER
hands and feet, pectus excavatum, scoliosis,
genital pigmentation, hemangiomatosis J aundice
• Mutation in PTEN tumor suppressor gene
• Yellow-green coloration of skin, conjunctivae
due to increased bilirubin
Familial Adenomatous Polyposis • Indirect bilirubin (unconjugated)—break-
(FAP) down product of red blood cells before liver
conjugation
• More common than other polyposis syn- –– High indirect bilirubin is usually due to
dromes: 3 in 10,000 live births hemolysis
• Cancer risk—if polyps not detected and –– Newborn hyperbilirubinemia is due to
treated, all will develop colorectal cancer increased indirect bilirubin
• Hundreds to thousands of adenomatous pol- –– Usually hematologic problem and not a GI
yps can develop in colon—gastric fundic pol- problem
yps can comprise 50% of total but do not • Direct bilirubin (conjugated) breakdown
require treatment product of red blood cells that has been con-
• Associated conditions: Increased risk of hep- jugated by the liver to make it water soluble
atoblastoma in childhood, increased risk of –– Increased direct bilirubin greater than 15%
malignancy of ampulla of Vater and duodenal of total is due to liver disease
790 R. D. Baker
Neonatal Cholestasis Table 22.12 Diagnostic screening tests for infants with
direct hyperbilirubinemia
• Accumulation of substances that should be Name of test
excreted in the bile (essentially equivalent to Abdominal ultrasound
Adenovirus
direct hyperbilirubinemia)
Alpha-1-antitrypsin phenotype
• Biliary atresia, idiopathic neonatal hepatitis, Alpha-1-antitrypsin level
and alpha- 1-
antitrypsin deficiency account Blood for organic acids
for over 80% of cases Cytomegalovirus (IgM) urine
• Causes of neonatal indirect Epstein-Barr virus titers
Ferritin
hyperbilirubinemia
Galactose-1-uridyl transferase
–– Anatomic Gamma-glutamyl transferase
–– Infectious Hepatitis B virus by PCR
–– Metabolic Hepatitis C virus by PCR
–– Genetic Herpes (IgM)
HIDA scan (pretreated with phenobarbital)
–– Toxic Lactate
–– Miscellaneous Parvovirus
Percutaneous liver biopsy
Pyruvate
Biliary Atresia Rubella (IgM)
Serologic test for syphilis (IgM and IgG)
Serum alkaline phosphatase
• The result of an idiopathic inflammatory pro-
Serum iron and total iron binding capacity
cess damaging intra- and extrahepatic ducts. Skull radiograph
End result of fibrosis and oblation of biliary Sweat test or stool elastase
tract, cirrhosis, and liver failure Thyroid screen
• Syndromic forms associated with other Toxoplasmosis (IgM)
Urine for amino acids
anomalies: Polysplenism, asplenism, portal Urine for bile acid analysis
vein malformations, malrotation, duodenal Urine for organic acids
and esophageal atresia, polycystic kidneys, N.B. Start phenobarbital treatment immediately
renal agenesis Rule out potentially treatable viral infections first
• Non-syndromic form without other anoma- IgM Immunoglobulin M, PCR Polymerase chain reaction, HIDA
lies more frequent Hepatobiliary iminodiacetic acid, IgG Immunoglobulin G
• Clustering in time and place points to an envi-
ronmental/infectious etiology, but none has Diagnosis (Table 22.12)
been identified • Ultrasound may show a small or absent
gallbladder
Clinical features
• Hepatobiliary iminodiacetic acid (HIDA)
• Jaundice (predominantly direct hyperbiliru-
scan shows absent excretion—but this is not
binemia) and acholic stools—child born at
specific
term and does well for 1st month
• Liver biopsy early shows bile duct prolifera-
• Splenomegaly, hepatomegaly
tion and bile canalicular stasis. Later increased
• Later ascites, wasting, and failure to thrive
fibrosis and bile duct drop out
Surgery Diagnosis
• Kasai procedure—hepatoportoenterostomy • Ceruloplasmin less than 20 mg/dL
• Intraoperative cholangiogram may precede • Hepatic copper greater than 250 μg/g dry
surgical procedure weight
• Attempt to establish bile duct drainage. More • Urine copper greater than 100 μg/24 h
successful if done early, i.e., before 8 weeks • Presence of Kayser-Fleischer rings
of age • Genotyping identification of 2 disease-caus-
• Results are variable—improvement seen in ing mutations in ATP7B
weeks or years
• A bridge to liver transplant—can be 1 year to Treatment
20 years of age—usually about 3 years • Copper chelators—D-penicillamine and tri-
• Primary transplant can be an option—size entine used in initial therapy and
limits to organs available maintenance
• Zinc acetate—inhibits copper absorption—
useful for maintenance and during
Wilson Disease pregnancy
• Treatment is lifelong
• Hepatolenticular degeneration—autosomal
recessive copper storage disease due to a
defect in incorporation of copper into cerulo- Gilbert Syndrome
plasmin → buildup of copper in body tissues
• Defect in ATP7B gene—no defect in cerulo- Background
plasmin gene, but rapid excretion of cerulo- • Common—heterogeneous group—all have
plasmin because of lack of copper an at least 50% reduction in UGT1A1 gene
incorporation (aceruloplasminemia) coding for UDP- glucuronosyltransferase
• Presents in the second to fourth decade but enzyme, the enzyme responsible for conju-
has been diagnosed in the elderly gating bilirubin. Complete absence of this
enzyme causes severe Crigler-Najjar syn-
Hepatic presentation drome (Table 22.13)
• Acute hepatitis, acute liver failure, chronic
hepatitis, steatohepatitis, portal hypertension, Presentation
cirrhosis, elevations of serum aminotransfer- • Causes mild unconjugated hyperbilirubine-
ase, gallstones, hepatocellular carcinoma mia, up to 4 mg/dL and minimally elevated
transaminases
Neuropsychiatric presentation • Picked up after puberty, routine screening, or
• Tremors, coordination defects, dystonia, conjunctival icterus
ataxic gate, fixed grin, headaches, seizures, • May cause mild fatigue
dementia, neurosis anxiety, depression, bipo-
lar, antisocial behavior Diagnosis
• Can be presumptive in the right setting, but
Other less common presentations rule out Wilson disease
• Renal (damage due to copper buildup) • In the Caucasian, homozygous finding of
• Hematologic (intravascular hemolysis) extra TA repeat in TATA box, (TA)7-TAA
• Cardiac, skeletal abnormalities (bone demin- necessary for Gilbert syndrome
eralization due renal tubular dysfunction)
• Hormonal imbalance
792 R. D. Baker
Table 22.13 Differences between Gilbert syndrome and chin, bulbous nose tip (dysmorphologists
Crigler-Najjar syndrome types I and type II (milder) correctly identified Alagille’s facies 79%
Crigler-Najjar Crigler-Najjar of the time—casting doubt on specificity)
Gilbert syndrome syndrome type II syndrome type I
Defect in Partial activity of Complete absence
bilirubin UDP-GT of UDP-GT Outcomes
UDP-GT
• Severity of disease varies from life-threaten-
Mild elevation of Indirect bilirubin Serum indirect
indirect bilirubin levels ranging bilirubin levels ing to asymptomatic
< 5 mg/dL from 7 to 20 mg/ ranging from 20 to • About half will require liver transplant
dL 50 mg/dL • Complex heart disease and vascular anoma-
Asymptomatic Asymptomatic Jaundice develops lies account for further complications and
Jaundice Jaundice in the first few days
of life kernicterus
mortality
Fasting, febrile – Hypotonia, • About a 75% 10-year survival
illness, exercise deafness,
can exacerbate oculomotor palsy,
jaundice lethargy, and, Hepatitis A Virus (HAV)
ultimately, death
No treatment No treatment Phototherapy
Liver
transplantation• HAV is the most common cause of viral hepa-
UDP-GT Uridine diphosphate-glucuronosyltransferase titis worldwide
• No known animal reservoir
• Mode of transmission is fecal-oral route
Implications
• Risk factors include international travel to
• Essentially no life-altering or life-shortening
areas with poor hygiene, personal contacts,
complications
and foodborne outbreaks
• May decrease metabolism of irinotecan (a
• Incubation period is 15–50 days
chemotherapeutic agent)
• Highest period of communicability is 1 week
before and after the onset of symptoms
Alagille Syndrome • CD8 + T cells are responsible for the destruc-
tion of infected liver cells
• Autosomal dominant disorder with mutation
in JAG1 gene or the NOTCH2 gene. Liver Clinical presentation
histology can be confused with biliary • In children younger than 5 years may be
atresia asymptomatic or with just few symptoms
• Older children and adults may develop symp-
Clinical features toms of acute infection which may last
• Paucity of intrahepatic ducts plus at least 3 of 2 weeks to several months
the following: • Symptoms include malaise, anorexia, fever,
–– Cholestasis nausea, vomiting, and eventually jaundice
–– Cardiac disease (often peripheral pulmonic • Most cases generally resolve without sequelae
stenosis) within a few weeks
–– Skeletal malformations (“butterfly”
vertebrae) Diagnosis
–– Ocular anomalies (posterior embryotoxon) • Anti-hepatitis A virus immunoglobulin M
–– Alagille’s facies—prominent forehead, (IgM) in a single serum sample is a good test
deep-set eyes, mild hypertelorism, pointed for current or recent infection (< 6 months)
Prevention Clinical presentation

• HAV vaccine at 12 months and booster dose • Acute self-limited hepatitis:
at least 6 months after the initial dose –– Increase in serum transaminases and reso-
• Prevention of HAV infection can be promoted lution of the infection within 6 months
by enforcing good hygiene in child care cen- –– Nausea
ters, with conscientious hand washing after –– Fever
changing diapers and before handling food –– Abdominal pain
• If traveling is imminent to endemic areas –– Jaundice, fatigue
(< 2 weeks) or the patient is immunocompro- –– General malaise
mised, immunoglobulin (IG) can be adminis- –– Papular acrodermatitis (Gianotti-Crosti
tered simultaneously with vaccine syndrome) that also manifests with EBV
• One dose of vaccine given at least 2 weeks infection
before departure is sufficient for travelers to • Fulminant hepatitis:
endemic areas. Give booster after return –– Acute hepatitis associated with a change in
6 months after first dose mental status due to hepatic
• Postexposure prophylaxis: encephalopathy
–– Administer HAV vaccine ASAP and within • Chronic hepatitis:
2 weeks of exposure –– Younger age at time of infection deter-
–– If cannot be vaccinated or immunocom- mines if chronic infection develops. Risk
promised, give IVIG ASAP and within for chronic infection is:
2 weeks of exposure ◦◦ 90% of infants
◦◦ 25–50% in children ages 1–5
◦◦ 5–10% in older children and
Treatment adolescents
• Supportive –– Generally, is asymptomatic in childhood,
• Avoid acetaminophen, it can exacerbate dam- having minimal or no effect on growth and
age to liver cells development, with normal or minimally
elevated serum ALT
Prognosis
–– Chronic infection increases risk for hepa-
• HAV does not carry the risk of chronic
tocellular carcinoma
infection
• Immunity after infection is lifelong Hepatitis B viral serology and liver functions
tests
Serologic marker for hepatitis B infection
Hepatitis B Virus (HBV) (Table 22.14) [4]
Background and epidemiology • HBsAg is the first serologic marker to appear
• The infection has an incubation period of and found in infected persons; its rise corre-
3 months lates with the acute symptoms
• HBV is commonly transmitted via body flu- • Anti-HBc is the single most valuable sero-
ids such as blood, semen, and vaginal logic marker of acute HBV infection, because
secretions it appears as early as HBsAg and continues
• HBV does not spread by breastfeeding, kiss- later in the course of the disease when HBsAg
ing, hugging, sharing utensils disappeared
• Perinatal transmission occurs during delivery • Anti-HBs marks serologic recovery and pro-
such that without prophylaxis, 70–90% of tection and marks vaccine immunity
exposed infants are infected
794 R. D. Baker
Table 22.14 Serologic markers for hepatitis B infection • Test reflecting liver failure
Marker Definition Detection Meaning –– High prothrombin time, despite adminis-
HBsAg Hepatitis B RIA/EIA Active HBV tration of vitamin K
surface antigen infection –– Low-serum albumin concentrations are the
Anti- Antibody to RIA/EIA Resolving or past
HBs HBsAg infection
most useful indicators of impaired syn-
Protective thetic liver function
immunity • HBV perinatal infection
Immunity from –– Nearly all perinatally acquired HBV infec-
vaccination tion are asymptomatic
HBeAg Nucleocapsid RIA/EIA Active infection,
derived Ag active viral –– Maternal screening of all pregnant women
replication for HBV is now standard
Anti- Antibody to RIA/EIA Cessation of –– Prophylaxis for all newborns of HBV-
HBe HBeAg replication or positive women in the first 12 h after birth:
replicating precore
◦◦ Combination of passive (hepatitis B
mutant
HBV- HBV viral PCR Active infection, IgG) and active immunization (first dose
DNA DNA loss means of the vaccine) followed by the complete
resolution HBV vaccine schedule
HBcAg Core antigen Detected only in –– Maternal anti-hepatitis antibody can per-
of HBV liver Sensitive
sist in infant for up to 18 months, which
indicator of
replication complicates testing
Anti- Antibody to RIA/EIA Recent infection –– Breastfeeding does not increase transmis-
HBc- HBcAg sion risk
IgM
Adapted from Wylie et al. [4], with permission
HBV hepatitis B virus, RIA radioimmunoassay, EIA enzyme Treatment
immunoassay • Treatment is mostly supportive, but FDA-
approved therapies exist to prevent progres-
• Both Anti HBs and Anti HBc are detected in a sion to cirrhosis, liver failure, and
person with resolved infection hepatocellular carcinoma
• HBeAg is present in person with active acute • Interferon therapy is approved, but treatment
or chronic infection and marks infectivity is long, filled with complications, and does
• Anti-HBe marks improvement and is the goal not always work
of therapy in chronically infected patients • Nucleotide analogue tenofovir, approved for
• Remember: Alanine transaminase (AST) and children 12 years and older, provides long-
aspartate aminotransferase (ALT) can be term viral suppression. Cure rates not known.
derived from muscle; you should verify that –– Interferon-alpha (Interferon-alpha2b,
serum creatine kinase and aldolase values are pegylated interferon alpha-2a)
within the normal range before assuming that –– Nucleoside analogs (entecavir, lamivudine,
the elevated serum AST and ALT values are and telbivudine)
hepatic in origin –– Nucleotide analogs (tenofovir and adefovir)
• Tests reflecting cholestasis
–– High-serum concentrations of gamma-
Vaccination
glutamyltransferase (GGT)
• Passive (hepatitis B immunoglobulin [HBIG])
–– High-serum alkaline phosphatase
and active (HBsAg) immunization decrease
–– High conjugated bilirubin
perinatal transmission
• Universal active immunization (three-dose –– Measure serum anti-HCV antibody at

regimen) recommended by World Health 18 months of age due to persistence of
Organization—177 countries have followed maternal antibodies
recommendations –– Anti-HCV antibody detection 97% sensi-
• Vaccination programs have decreased the tive and 99% specific but not useful in
prevalence of HBV disease and hepatocellu- infants of HCV- positive mothers until
lar carcinoma 18 months of age
–– May not pick up early infection
• The HCV RNA by polymerase chain reaction
Hepatitis C Virus (HCV) (PCR) test can be either qualitative (used for
diagnosis) or quantitative (used to monitor
• RNA (ribonucleic acid) virus of the disease activity). “Not detected” does not
Flaviviridae family—mutates rapidly lead- mean that there is no virus in the sample
ing to many genotypes and subtypes with • Know that children with chronic hepatitis C
geographic differences in distribution. Also infection should undergo periodic screening
complicates the task of developing a tests for hepatic complications and the treat-
vaccine ment regimens are available
• Infection is common in adults—less common
in children Symptoms and outcomes
• Acute HCV infection in childhood and ado-
Transmission lescence is relative asymptomatic
• Requires “blood to blood.” Divide into “per- • There are rare examples of “rapid progres-
cutaneous” and “non-percutaneous” sion,” reason unknown
–– Blood and blood products no longer a • There have been cases of spontaneous clear-
source of infection ance of virus up to age 11 years
–– Most common mode of transmission in • It is likely that liver damage and disease will
children is perinatal progress with age. HCV is the most common
–– Second most common is associated with reason for liver transplant in the USA
illegal drug use. Tattoos have been sus-
pected but no conclusive answer Treatment
–– Perinatal transmission occurs in approxi- • Direct acting antivirals (DAA) have been
mately 5% of HCV-positive pregnancies. approved for children 12 and over
20% of these infants clear the infection • DAAs are 100% effective, relatively
spontaneously complication-free
• Delay treatment until a DAA regimen can be
implemented. Treatments are expensive and
Diagnosis insurers have resisted paying for the treat-
• HCV infection is investigated by measuring ment. But cost benefit is in favor of treatment
anti-HCV antibody and is confirmed by the • Therapies are approved for adults - changes a
detection of serum HCV RNA by PCR. At likely as new drugs become available
least 2 positive tests are needed to diagnosis • Genotypes 1a and 1b:
HCV infection –– Ledipasvir and sofosbuvir
• Screening of infants born to HCV-infected –– Ombitasvir, dasabuvir, and paritaprevir,
mothers: with or without ribavirin
–– Grazoprevir, elbasvir
796 R. D. Baker
• Genotype 2: • Liver transplant in about 8%—frequent

–– Sofosbuvir plus ribavirin or daclatasvir recurrence in transplanted liver—mortality
• Treatment for 12–24 weeks about 5%
Autoimmune Hepatitis (AIH) Hepatomegaly

• Unknown etiology—plasma cell and mono- Background
cyte infiltrate portal tracts • Hepatomegaly more than 3.5 cm below the
• Two types—both have female predominance right costal margin in newborn
–– Type I (classic AIH) characterized by the • Hepatomegaly more than 2 cm below the
presence of antinuclear antibody (ANA), right costal margin in children
antismooth-muscle antibody (ASMA),
anti-actin, anti-asialoglycoprotein receptor Causes of liver diseases in children and
–– Type II (anti-LKM-1 AIH) anti-liver-kid- adolescents
ney microsome antibodies—occurs at a • Hepatitis
younger age and is more resistant to treat- –– Viral
ment—more likely to have extrahepatic –– Autoimmune
autoimmune phenomenon (thyroiditis, –– Toxic
ulcerative colitis, etc.) –– Drug related
• Wilson disease
Presentation and diagnosis • Budd-Chiari syndrome (hepatic vein
• Symptoms range from minimal fatigue, jaun- obstruction)
dice to severe jaundice, dark urine, elevated • Fatty liver disease
aminotransferases, and coagulopathy • Congestive heart failure
• Needs to be distinguished from other causes • Storage liver disease
of hepatitis—hepatitis A virus, HBV, HCV, –– Fat
Wilson disease –– Nonalcoholic steatohepatitis (NASH)
• Liver biopsy revealing mononuclear and plasma –– Rey syndrome
cell infiltration of the portal tracts is helpful –– Glycogenesis
–– Mucopolysaccharidosis
Treatment and outcome
• Responds to immunosuppression
• Induction of remission—oral prednisone Evaluation of hepatic dysfunction (initial
until normalization of aminotransferases— evaluation)
can be prolonged time (6–12 months) • CBC
• Maintenance of remission—azathioprine or • Reticulocyte count
6-mercaptopurine • Comprehensive metabolic panel
• Pulse with steroids for relapses • Fractionated bilirubin
• Immunosuppression can be discontinued • ESR
after at least 3 years of treatment, 1 year of • Gamma-glutamyl transpeptidase
normal aminotransferases, and normal or • PT
near-normal biopsy
Evaluation for the etiology of liver dysfunction PEARLS AND PITFALLS

• Hepatitis serologies A, B, and C
• Alpha-1-antitrypsin • Listen to your patient and the family of the
• Alpha-fetoprotein patient. They know better than you what is
• Serum ceruloplasmin going on. Don’t be judgmental.
• Antinuclear antibodies • Unwitnessed foreign bodies within the air-
• Antismooth muscle antibodies way have the potential to masquerade as more
• Anti-liver/kidney microsomal antibodies common diseases such as croup and bronchi-
• Sweat chloride olitis/asthma.
• Serum lipid profile • Esophageal foreign bodies have the potential
to cause significant airway compromise.
• Impaction is often to underlying pathology
Portal Hypertension such as eosinophilic esophagitis, GERD, and
known prior strictures.
Background • Always rule out Wilson disease in any teen-
• Elevation of portal pressure > 10–12 mmHg ager with hepatitis. It is treatable but serious
• Major cause of morbidity and mortality in if it is missed.
children with liver disease • Treat constipation vigorously. The “go slow”
• In children, extrahepatic obstruction due to approach usually does not work.
portal vein thrombosis is the most common • Track growth, weight gain, and development.
cause These are the clues that something may be
• Cavernous transformation (extensive col- wrong.
lateral of small blood vessels from para-
choledochal and epicholedochal venous
system) References
• In children with biliary atresia, CF, and other
liver diseases, the incidence of intrahepatic 1. Hyams JS, Di Lorenzo C, Saps M, Shulman RJ,
obstruction causing portal hypertension is Staiano A, van Tilburg M. Childhood functional
increasing as they survive longer gastrointestinal disorders: child/adolescent.
Gastroenterology. 2016;150(6):1456–68.e2.
Clinical presentation 2. Nelson R, Sreedharan R, Liacouras CA.
• Bleeding from esophageal varices is the most Digestive system. In: Kliegman RM, Stanton
common presentation BF, Schor NF, St. Geme III JW, Behrman RE,
• Cholestasis and liver dysfunction with ele- editors. Nelson textbook of pediatrics. 19th ed.
vated serum bilirubin and transaminases may Philadelphia: Elsevier Saunders; 2011. p. 1242.
occur in portal vein obstruction 3. Kramer RE, Lerner DG, Lin T, Manfredi M,
Shah M, Stephen TC, North American Society
Diagnosis for Pediatric Gastroenterology, Hepatology,
• Ultrasound, CT, or MRI and Nutrition Endoscopy Committee, et al.
Management of ingested foreign bodies in
Management children: a clinical report of the NASPGHAN
• Endoscopic treatment of esophageal varices endoscopy committee. J Pediatr Gastroenterol
and liver transplantation Nutr. 2015;60(4):562–74.
798 R. D. Baker
4. Wylie R, Hyams JS, Kay M, editors. Pediatric Hyams JS, Di Lorenzo C, Saps M, Shulman RJ,
gastrointestinal and liver disease. 5th ed. Staiano A, van Tilburg M. Childhood functional
Philadelphia: Elsevier; 2016. gastrointestinal disorders: child/adolescent.
Gastroenterology. 2016;150(6):1456–68.e2.
Kleinman RE, Goulet O-J, Mieli-Vergani G,
Suggested Reading Sanderson IR, Sherman PM, Shneider BL, edi-
tors. Walker’s pediatric gastrointestinal disease.
Green SS. Ingested and aspirated foreign bodies. 6th ed. Raleigh: People’s Medical Publishing
Pediatr Rev. 2015;36(10):430–6. quiz 437 House–USA; 2018.
Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano Sierra D, Wood M, Kolli S, Felipez LM. Pediatric
A, Guandalini S, North American Society for gastritis, gastropathy, and peptic ulcer disease.
Pediatric Gastroenterology, Hepatology and Pediatr Rev. 2018;39(11):542–9.
Nutrition, et al. Guideline for the diagnosis and Suchy FJ, Sokol RJ, Balistreri WF, editors. Liver
treatment of celiac disease in children: recom- disease in children. 4th ed. Cambridge, UK:
mendations of the North American Society Cambridge University Press; 2014.
for Pediatric Gastroenterology, Hepatology Wylie R, Hyams JS, Kay M, editors. Pediatric
and Nutrition. J Pediatr Gastroenterol Nutr. gastrointestinal and liver disease. 5th ed.
2005;40(1):1–19. Philadelphia: Elsevier; 2016.
Nephrology
23
Beatrice Goilav
GENERAL Proteinuria
Normal Renal Function Definition

• Dipstick 1 + or 30 mg/dL is considered
• Glomerular filtration increases progressively proteinuria.
from day 1 after birth and continues to
increase with growth until the second year of Dipstick
life. • Negative.
• If corrected for surface area, the glomerular • Trace means 10–20 mg/dl.
filtration rate (GFR) reaches adult values of • 1 + means 30 mg/dl.
120 cc/min/1.73 m by 2 years of age.
2 • 2 + means 100 mg/dl.
• 3 + means 300 mg/dl.
Creatinine Level • 4 + means 1000–1500 mg/dl.
• Serum creatinine may be elevated in the first
10 days of life, reflecting the maternal Consider False Positive
creatinine. • Too concentrated urine, e.g., specific gravity
• Infant: 0.2–0.4 mg/dL. (SG) > 1.015 and protein < 2 +.
• Child: 0.3–0.7 mg/dL. • Consider false negative if SG < 1.005 and
• Adolescent: 0.5–1.0 mg/dL. protein negative.
• Adult male: 0.9–1.3 mg/dL. For adult males,
Diagnosis
higher values correspond to the higher mus-
• First morning sample immediately in the
cle mass compared to females.
morning (important to instruct the child to
• Adult female: 0.6–1.1 mg/dL.
empty the bladder before going to sleep the
night before the test in the morning and to
minimize upright position and walking).
• Divide urine protein/creatinine ratio (UPr/
UCr), if ≤ 0.2 is normal in child > 2 years of
age.
• If dipstick > 1 + or UPr/UCr > 0.2 on repeat
urine morning sample, the patient should be
B. Goilav (*) referred to a nephrologist for evaluation of a
Pediatric Nephrology, Children’s Hospital at Montefiore, Albert
Einstein College of Medicine, Bronx, NY, USA renal disease.
e-mail: bgoilav@montefiore.org

800 B. Goilav
• Dipstick 3 + or greater suggests nephrotic- Causes of Discolored Urine with Negative Urine
range proteinuria. Dipstick and Urine Microscopic Examination
• On 24 h urine collections, protein < 4 mg/ • Medications, e.g., sulfonamides, nitrofuran-
m /h is normal, and nephrotic-range protein-
2
toin, and salicylates.
uria is greater than 40 mg/m /h.
2
• Food coloring, beets, and blackberries.
• In newborns, a red or pink discoloration in
Orthostatic Proteinuria the diaper can be seen when urate crystals
• Significant proteinuria in upright position and precipitate from the urine.
resolved in supine position
• Presence of proteinuria with UPr/UCr greater Clinical Approach to a Child with Gross
than 0.2 on random urine specimen but less Hematuria
than 0.2 on first morning specimen • Confirm the diagnosis by microscopy.
• Benign condition, no further workup or treat-
ment necessary
Glomerular Hematuria
Transient Proteinuria
• Dipstick is > 1 + with a subsequent negative • Discolored urine (tea or cola colored), RBC
test. casts, and dysmorphic RBC morphology
• Common causes: exercise, fever, intercurrent
illness, and stress. Causes
Persistent Proteinuria • Postinfectious glomerulonephritis—2 weeks
• Persistent proteinuria is the signal indicator after infection
of renal disease. • Lupus nephritis (LN)—malar rash, joint pain,
• Positive first voided morning specimen > 1 + anemia
protein on dipstick or UPr/UCr > 0.2—repeat • Alport disease—young men with sensorineu-
with 2-week interval and rule out intercurrent ral hearing loss and ocular abnormalities
illnesses. • Immunoglobulin A (IgA) nephropathy—
gross hematuria with upper respiratory tract
infections or acute gastroenteritis (stimula-
Hematuria tion of IgA production)
Definition • Membranoproliferative glomerulonephritis
• Presence of five or more red blood cells (MPGN)—intermittent gross hematuria, per-
(RBCs) per high-power (400×) field in 3 consistent C3 hypocomplementemia (also trig-
secutive fresh, centrifuged specimens gered by infections)
obtained over the span of several weeks. • Henoch-Schönlein purpura
• Microscopic hematuria = urine grossly • Hemolytic uremic syndrome (HUS)—dark
appears normal; gross hematuria = blood is urine, hypertension (HTN), oliguria, pallor,
visible to the naked eye. anemia, history of schistocytes on peripheral
• Confirmation of hematuria is critical, i.e., smear, thrombocytopenia, and history of
presence of RBCs in urine sediment. bloody diarrhea
Laboratory
Causes of False-Positive Urine Dipstick for • Complete blood count (CBC), comprehen-
Hematuria sive metabolic panel (CMP), serum protein,
• Myoglobinuria or hemoglobinuria, negative cholesterol, C3, C4, antistreptolysin O (ASO),
for RBCs on microscopic evaluation
23 Nephrology 801
anti-deoxyribonuclease (DNase) B, antinu- nant—adults in approximately the fifth

clear antibodies (ANA), antineutrophil cyto- decade)
plasmic antibodies, throat culture, and UPr/ • Trauma
UCr • Meatal stenosis
• Hepatitis and HIV serologies • Coagulopathy
• Renal vein thrombosis (RVT)
Non-glomerular Hematuria Diagnostic Workup for Extraglomerular

Causes
• Normal RBC morphology. • Urine culture
• Presence of clots—urine may be brown due • Urine calcium (Ca)/Cr ratio (normal is
to clot in the bladder. ≤ 0.2 in adults and children > 8 years old, but
• May be accompanied by dysuria. may be higher in younger children and
infants)
Causes • Renal/bladder ultrasound looking for debris
• Pyelonephritis or stone
• Cystitis • If for crystalluria, urolithiasis, or nephrocalci-
• Hemoglobinopathy, such as sickle cell ane- nosis: 24 h urine for Ca, creatinine, uric acid,
mia (trait) oxalate, cysteine, and citrate levels
• Nephrocalcinosis
• Kidney stones (most common: calcium (Ca)
oxalate stone) Idiopathic Hypercalciuria [1]
• Hypercalciuria, caused by the following:
–– Idiopathic hypercalciuria caused by condi- Etiology
tions resulting in hypercalcemia • May be inherited as an autosomal dominant
–– Hyperparathyroidism disorder
–– Vitamin D intoxications • May be caused by conditions resulting in
–– Immobilization hypercalcemia
–– Loop diuretics • Hyperparathyroidism
–– Sarcoidosis • Vitamin D intoxication
–– Cushing syndrome • Immobilization
–– Corticosteroid therapy • Loop diuretics
–– Williams syndrome • Sarcoidosis
–– Bartter syndrome • Cushing syndrome
–– Dent disease (X-linked recessive condition • Corticosteroid therapy
of the proximal tubule, characterized by • Williams syndrome
tubular proteinuria, hypercalciuria, and • Bartter syndrome
chronic kidney disease) • Dent disease (X-linked nephrolithiasis)
• Hyperoxaluria (primary [genetic], enteric
Clinical Presentations
[malabsorption syndromes], or secondary
• Recurrent (+/− painful) gross hematuria
[high consumption of oxalate-rich foods])
• Microscopic hematuria
• Tumor
• Diffuse abdominal pain
• Polycystic kidney disease (autosomal reces-
sive—in infancy, in utero; autosomal domi-
802 B. Goilav
Table 23.1 Screening of high blood pressure (BP) and hypertension (HTN) in children and adolescents—American
Academy of Pediatrics Clinical Practice Guideline 2017 (Flynn et al. [2])
Age Normal BP (mmHg) Elevated BP (mmHg) Stage 1 HTN (mmHg) Stage 2 HTN (mmHg)
1– < 13 years < 90th percentile ≥ 90th percentile to ≥ 95th percentile to < 95th ≥ 95th percentile + 12
< 95th percentile percentile + 12
or or or
120/80 to < 95th 130/80 to 139/89 ≥ 140/90
percentile
(Whichever is lower) (Whichever is lower) (Whichever is lower)
≥ 13 years < 120/< 80 120/< 80 to 129/< 80 130/80 to 139/89 ≥ 140/90
Diagnosis the adult guidelines, which consider every

• 24-hour urine collection to measure urinary cal- BP > 120/80 mmHg as elevated.
cium concentration (has to be > 4 mg/kg/day). –– Elevated BP has to be confirmed on 3 dif-
• Spot urine Ca/Cr ratio > 0.2 suggests hyper- ferent occasions in the outpatient setting.
calciuria in a child > 8 years old. • There is no definition for the diagnosis of
• Normal ratio may be as high as 0.8 in infants HTN in the inpatient setting; therefore, one
< 7 months. should refrain from making this diagnosis
while the patient is acutely ill.
Treatment
• If untreated, 15% develop nephrolithiasis. Proper Technique When Measuring BP
• Hydrochlorothiazide 1–2 mg/kg/24 h as single • Correct cuff size to a child’s bare arm:
morning dose, with dose titration until the 24 h –– Bladder width that is at least 40% of the
urinary calcium concentration is < 4 mg/kg/day child’s midarm circumference.
and clinical manifestations resolve. –– Bladder length that encircles 80–100% of
• Sodium restriction leads to decreased sodium the midarm circumference.
excretion and increased reabsorption of cal- –– After the child has been sitting for 5 min
cium from the urine (lowers calcium concen- with both feet on the ground.
tration in urine). –– All BP elevations must be confirmed by
manual auscultation
Hypertension [2] Causes of HTN (List Not All-Inclusive)

• Primary HTN is less common in the pediatric
Definition population, but on the rise due to increase in
• Pediatric HTN is sustained elevation of either prevalence of obesity and metabolic syn-
the systolic or diastolic blood pressure (BP) drome among adolescents.
at or above the 95th percentile of BP for a • Secondary causes become more common in
child’s age, gender, and height percentile or younger patients and should always be ruled
equal or greater than 130/90 mmHg in chil- out, even if the patient is obese.
dren aged 13 years and older. • Cardiac:
• The age- and height-specific BP percentiles –– Coarctation of the aorta—BP discrepancy
were adjusted to children with normal BMIs between arms and legs; leg BP equal to or
and are therefore lower in the new guide- lower than arm BP
lines. (Table 23.1) [2]. • Renal:
• Elevated BP ≥ 90th percentile: –– Autosomal recessive polycystic kidney
–– The BP threshold has been changed for disease in newborns or autosomal domi-
children aged 13 years and above to match
23 Nephrology 803
nant polycystic kidney disease in older –– Erythropoietin

children and adolescents –– Stimulants for treatment of attention deficit
–– Congenital renovascular abnormalities disorder
–– Reflux nephropathy • Syndromes:
–– Obstructive uropathy –– Williams syndrome:
–– Glomerulonephritides ◦◦ Supravalvular aortic stenosis
–– HUS ◦◦ Midaortic syndrome
–– Urinary tract infections ◦◦ Renal artery stenosis
–– Chronic pyelonephritis ◦◦ Renal anomalies
–– Renal cortical scars –– Neurofibromatosis:
–– Nephrotoxic medications ◦◦ Renal artery stenosis
• Pulmonary:
–– Pulmonary HTN: Clinical Approach to the Child with HTN
◦◦ Bronchopulmonary dysplasia • All children diagnosed with HTN should
◦◦ Obstructive sleep apnea undergo an evaluation to investigate for sec-
• Neurological: ondary causes of HTN.
–– Increased intracranial pressure: • Initial evaluation:
◦◦ Hemorrhage –– Focused history and physical examination
◦◦ Tumor –– Urinalysis:
–– Pain ◦◦ Hematuria, proteinuria, or pyuria
• Neoplastic: –– Blood urea nitrogen (BUN)/creatinine
–– Wilms tumor –– CBC:
–– Neuroblastoma ◦◦ Anemia secondary to renal disease or
• Endocrine: chronic condition
–– Congenital adrenal hyperplasia – – Electrolytes:
–– Hyperaldosteronism ◦◦ Hyper or hyponatremia
–– Hyperthyroidism ◦◦ Hyper or hypokalemia
• Prematurity and low birth weight: ◦◦ Hypercalcemia
–– Renal artery stenosis –– Evaluation for metabolic syndrome:
–– Renal vein thrombosis ◦◦ Lipid profile
–– Multiple intrarenal thrombi after removal ◦◦ Fasting blood glucose
of the umbilical artery line –– Pregnancy test:
• Over-the-counter medications: ◦◦ Preeclampsia
–– Decongestants/cold preparations –– Renal and bladder ultrasound with Doppler:
–– Herbal medications/supplements ◦◦ Renal masses, e.g., Wilms tumor.
• Other medications: ◦◦ Renal scars.
–– Corticosteroids ◦◦ Severe hydronephrosis due to uretero-
–– Calcineurin inhibitors (cyclosporine, pelvic junction obstruction with
tacrolimus) impaired renal blood flow.
–– Nonsteroidal anti-inflammatory medications ◦◦ Doppler measures resistive indices of
–– Caffeine blood flow to the kidneys:
–– Oral contraceptive pills ▪▪ Any abnormality, especially together
–– Abrupt discontinuation of long-acting anti- with size discrepancy between the
hypertensive medications kidneys, should prompt further imag-
–– β-Adrenergic agonists/theophylline ing studies, e.g., magnetic resonance
angiogram (MRA) or angiogram.
804 B. Goilav
–– Echocardiography: –– Angiotensin receptor blockers.

◦◦ Structural heart disease, e.g., coarctation –– β-Blockers (not for patients with known
of the aorta asthma or diabetes mellitus [DM]).
◦◦ Left ventricular hypertrophy (LVH) sec- –– Diuretics.
ondary to prolonged HTN –– The lowest dose should be started, titrating
to effect until the maximum recommended
Treatment dose is achieved or until the patient experi-
• If it’s secondary HTN, treat underlying ences adverse effects.
condition.
• If it’s primary HTN:
• Lifestyle modification: PERSISTENT PROTEINURIA
–– Weight loss if overweight.
–– Moderate-to-vigorous aerobic exercise. Nephrotic Syndrome
–– Increase intake of fresh vegetables, fruits,
and low-fat dairy foods. Definition
–– Reduce carbohydrate, fat, and processed • Proteinuria
sugar intake. • Hypoalbuminemia
–– Limit or avoid sugar-sweetened, caffein- • Edema
ated beverages. • Hypercholesterolemia
–– Salt restriction.
–– Smoking cessation, if applicable. Background
• Indication for antihypertensive • More common in males during childhood,
medications: equal gender distribution among adolescents.
–– If it’s symptomatic HTN, treat immedi- • Caused in 85% by minimal change disease in
ately (hypertensive emergency = evidence children, but in adolescents, most commonly
of end-organ damage—seizure, neurologi- due to focal segmental glomerulosclerosis
cal deficits, myocardial infarction, acute (FSGS).
kidney injury (AKI); hypertensive urgency • Minimal change disease refers to the patho-
= patient displaying symptoms associated logical picture in which the glomerulus looks
with potential organ damage—headache, normal on light microscopy, but on electron
blurry vision, chest pain, palpitations, and microscopy there is effacement of the podo-
dizziness). cyte foot processes.
–– Patients who have not experienced normal- • Common between 2 and 6 years of age.
ization of their BP with the above interven- • In adolescents, nephrotic-range proteinuria in
tions after 2 months. the absence of hypoalbuminemia may be due
–– LVH can develop within 2 months of to FSGS.
uncontrolled HTN.
–– Hypertensive retinopathy. Clinical Presentation
–– Diabetes mellitus (DM). • Periorbital and facial edema in the morning,
• The pharmacologic agents: lower extremity edema later in the day.
–– Calcium channel blocker. • Slow progression—facial edema may be
–– Angiotensin-converting enzyme (ACE) attributed to allergies at the beginning, caus-
inhibitors (first choice in diabetics, patients ing some delay in initial diagnosis.
with LVH, and patients with known • Overtime, edema becomes generalized,
chronic, proteinuric kidney disease). accompanied by ascites and pleural effusions.
23 Nephrology 805
• Abdominal pain and diarrhea are common; ◦◦ In younger children, oral cyclophospha-
HTN and hematuria are uncommon. mide with 2 mg/kg/day for 3 months
• HTN at presentation should raise the suspi- should be the second- line agent of
cion of an underlying nephritis with nephrotic- choice.
range proteinuria or of FSGS. ◦◦ In older children and adolescents, calci-
neurin inhibitors can be beneficial, but
Diagnosis relapses occur with discontinuation.
• Urinalysis reveals 4 + proteinuria. ◦◦ Mycophenolate mofetil, shows steroid-
• Microscopic hematuria in 20% of cases. sparing effect, but dosing guidelines are
• Spot urine protein /Cr ratio > 2. not evidence based.
• Urinary protein exceeds > 40 mg/m2/h. –– The use of steroid-sparing agents in ste-
• Serum creatinine value is usually normal. roid-resistant nephrotic syndrome can be
• Diminished renal perfusion due to decreased considered, but there is no evidence sug-
effective blood volume. gesting significant outcome improvement.
• Serum albumin < 2.5 g/dl. • Supportive treatment:
• Serum cholesterol and triglycerides are –– Sodium restriction as long as the patient has
elevated. nephrotic-range proteinuria.
• C3 and C4 are normal, and serologies related –– Water restriction, if hyponatremia.
to infections or autoimmune diseases are –– Diuretics.
negative. –– Admit, if hypertensive.
• Renal biopsy is not indicated unless < 1 year –– If fluid restriction and parenteral diuretic
or > 10 years or in any case that is not respon- are not effective, start intravenous (IV)
sive to steroids, i.e., the urine does not become 25% albumin 1 g/kg/dose (max. dose 50 g)
protein-free within 6 weeks of treatment with q 8–12 h followed by furosemide 1–2 mg/
high-dose steroids. kg/dose—monitor electrolytes.
–– If the patient is steroid resistant, antipro-
Treatment teinuric agents such as ACE inhibitors or
• Treating the underlying cause: angiotensin receptor blockers should be
–– First episode: prednisone 60 mg/m2/day added to the therapy.
divided into two doses for 6 consecutive
weeks, followed by 6 weeks of alternate- Complications
day therapy with 40 mg/m2/day. • Children with nephrotic syndrome are
–– Relapse: prednisone 60 mg/m2/day divided immunocompromised from the disease per
into two doses until the patient’s urine is se, because they lose IgG and important
negative for protein on 3 consecutive days, complement cofactors in the urine.
followed by 4 weeks of alternate-day ther- Infections are the most common complica-
apy with 40 mg/m2/day. tion; and among those, spontaneous bacte-
–– Confirm negative purified protein deriva- rial peritonitis (due to Streptococcus
tive (PPD) or Quantiferon test before pneumoniae, Escherichia coli, and group B
starting steroid therapy, if patient at high- Streptococci) needs to be suspected in a
risk for exposure to TB. child who has nephrotic syndrome and
–– If the patient has multiple relapses a year, abdominal pain. This an indication for
displays signs of steroid toxicity, or shows admission even in the absence of fever.
steroid dependence, a second-line agent is Ascitic fluid should be aspirated by a pedi-
to be considered (steroid-sparing agent): atric surgeon.
806 B. Goilav
• Once they are in remission, all children with plants, particularly if the patient presented
a diagnosis of nephrotic syndrome must at young age and progressed rapidly to
receive polyvalent pneumococcal vaccine if ESRD—exact causes of recurrence are not
not previously immunized. known (possible “circulating factor”).
• Varicella vaccine must be given for varicella-
negative children. FSGS may be due to genetic mutations in genes
• Thromboembolic events occur in 2–5% of related to podocyte architecture, but is not protec-
cases due to urinary loss of antithrombin III tive of recurrence after kidney transplantation,
and protein C and S. unless it is a known pathogenetic mutation as the
• Newborns, infants, and small children with underlying cause can still be due to a circulating
nephrotic syndrome may require thyroid hor- factor of idiopathic FSGS.
mone supplementation due to loss of
thyroglobulin-binding protein in the urine.
Membranous Nephropathy (MN)
Prognosis
• Children between the ages of 1 and 8 years Background
are usually steroid responsive, defined as • Most common cause of nephrotic syndrome
complete resolution of proteinuria within in adults
4 weeks of daily high-dose steroids.
Etiology
• 80 to 90% of patients will respond to steroid
• Can be a separate idiopathic renal disease or
therapy within 2 weeks.
associated with systemic lupus erythemato-
• If proteinuria continues after 6 weeks of ther-
sus (SLE) (WHO class V LN), drugs (penicil-
apy, a renal biopsy should be considered,
lamine, gold), toxins, or infections (hepatitis
because then the child, by definition, has ste-
B, malaria, syphilis). In adults, may be due to
roid-resistant nephrotic syndrome, even if there
auto-antibodies to M-type phospholipase A2
is some reduction in proteinuria.
receptor (PLA2r).
• Patients who relapse as soon as steroids are
discontinued or tapered are considered ste- Clinical Presentation
roid dependent. • Generalized edema due to nephrotic-range
• Only 30% of children with nephrotic syn- proteinuria:
drome have only one episode; relapses are –– 80% have concurrent microscopic
common and usually occur 2 to 3 times per hematuria.
year—any intercurrent illness can trigger a • Very rare in children—only 5% of nephrotic
relapse. syndrome in childhood is due to MN.
• Minimal change disease resolves in > 80% • Presence of HTN at presentation is an adverse
(child outgrows the disease), but children prognostic factor.
who presented at a younger age or who have
frequent relapses may continue relapsing into Diagnosis
adulthood. • Renal biopsy—degree of sclerosis also allows
• Steroid-sensitive nephrotic syndrome can prediction of prognosis.
convert to steroid resistant, at which point a • C3 is normal unless it is secondary to SLE.
renal biopsy is indicated. • Diffuse thickening of the glomerular base-
• 30% of FSGS cases respond to steroids ment membrane (GBM) (due to IgG and C3
initially. deposition) without proliferative changes.
• FSGS can progress to end-stage renal dis-
ease (ESRD) and can recur in kidney trans-
23 Nephrology 807
Treatment Complications, Prognosis, and Treatment

• Salt restriction and diuretics. • Iron and vitamin D deficiency due to loss of
• ACE inhibition reduces proteinuria. binding proteins (total iron saturation may be
• If the patient is nephrotic, treat with steroids. falsely resulted as > 100% because transfer-
If there’s no response, escalate to cyclophos- rin is lost in urine).
phamide and continue with tacrolimus or • Hypothyroidism (significant and requires
cyclosporine. It may recur after cessation of early treatment) due to loss of thyroid-binding
therapy globulin.
• Frequent infections due to loss of IgG.
Prognosis • Clots due to loss of antithrombin III.
• 2% of children progress to ESRD. • Symptomatic treatment requires daily substi-
tution of albumin (needs permanent IV place-
ment early).
Congenital Nephrotic Syndrome • Only bilateral nephrectomy is “curative,” and
the patient then has to be placed on peritoneal
Background
dialysis.
• Autosomal recessive.
• Genetic mutation in the nephrin gene
(NPHS1); nephrin is a protein that is part of Infantile Nephrotic Syndrome
the slit diaphragm.
• Also called “Finnish type” due to increased Background
frequency in Finnish population (1:8200 live • Group of nephrotic syndromes.
births). • 66% have underlying genetic mutation with-
out extrarenal manifestations.
• Nephrotic syndrome presenting between birth Clinical Presentation
and 3 months of age. • Steroid-resistant nephrotic syndrome pre-
• Edema may appear as late as several weeks senting between 4 and 12 months of age.
after birth, but urine shows nephrotic-range • Nephrotic syndrome may present alone or as
proteinuria at birth. part of a syndrome.
• > 80% born premature.
• Placenta enlarged, 25% of the baby’s birth Diagnosis
weight. • Genetic testing offers definitive diagnosis.
• Enlarged kidneys. • Most common genes affected: PLCE1 (phos-
• No extrarenal malformations. pholipase C, epsilon 1), CD2AP, ACTN4
• Severe intractable edema. (α-actinin 4), and TRPC6 (transient receptor
potential cation channel 6).
Diagnosis • Pierson syndrome is caused by LAMB2 muta-
• Commercially available genetic testing offers tions and presents with ocular abnormalities
definite diagnosis. (buphthalmos, microcoria).
• Differential diagnosis: TORCH and HIV • Wilms tumor, aniridia, genitourinary abnor-
infections can cause secondary nephrotic malities, and intellectual disability (ID) for-
syndrome and need to be ruled out first. merly known as mental retardation (WAGR)
syndrome is caused by PAX6 mutation
(important gene during development).
808 B. Goilav
• Biopsy may be nonspecific and shows diffuse • It may also follow S. pneumoniae, gram-
mesangial sclerosis. negative bacteria, bacterial endocarditis, or
viral infections, especially influenza.
Prognosis and Treatment
• Progression to ESRD at varying speeds Clinical Presentation
• No recurrence of disease in kidney • Most common in children between 5 and
transplant 15 years of age.
• 1 to 2 weeks after streptococcal pharyngitis
or 3–6 weeks after streptococcal pyoderma.
Frasier Syndrome • Nephritic presentation; various degrees of
edema, HTN, and oliguria.
Background • Encephalopathy and heart failure may
• Autosomal dominant, but mostly sporadic develop.
• Acute phase resolves in 6–8 weeks.
• Proteinuria and HTN should normalize within
• Male pseudohermaphroditism with normal
4–6 weeks after onset.
female external genitalia, but streak gonads
• Microscopic hematuria may persist for up to
• 46, XY
2 years, and the patient needs to be followed
• Onset of proteinuria at age 2–6 years
until its resolution.
• Steroid-resistant nephrotic syndrome
Diagnosis
Diagnosis
• Urinalysis: dysmorphic RBCs, RBC casts,
• Renal biopsy shows FSGS.
proteinuria, polymorphonuclear leukocytes.
Prognosis and Treatment • Mild normochromic anemia.
• Increased susceptibility to gonadoblastoma, • Low C3 ± normal; low C3 should return to
which requires removal of gonadal streaks normal within 6–8 weeks.
• No increased risk for Wilms tumor • Confirmation of diagnosis with positive throat
• Slow progression to ESRD in adolescence or culture.
early childhood • Positive ASO titer if related to streptococcal
• No recurrence of disease in kidney pharyngitis, but anti-DNase B level positive
transplant if related to skin nephritogenic strains
(impetigo).
• Indication for renal biopsy: rapidly progres-
PERSISTENT HEMATURIA/ sive glomerulonephritis (RPGN), C3 level
not normalizing beyond 8 weeks after the
PROTEINURIA acute illness, or persistent microscopic hema-
turia beyond 2 years’ duration.
Acute Postinfectious
Glomerulonephritis Management
• Early systemic antibiotics do not eliminate the
risk of glomerulonephritis, but family mem-
Etiology bers should be cultured and treated if positive.
• Most commonly caused by nephritogenic • 10-day course of antibiotics is recom-
toxins of group A beta-hemolytic strepto- mended to limit the spread of nephritogenic
cocci—usually presenting as streptococcal strains.
pharyngitis in cold weather and skin pyo- • Salt restriction.
derma in warm weather.
23 Nephrology 809
• Diuretics. Clinical Presentation

• Calcium channel blockers and ACE inhibitors • Recurrent episodes of gross hematuria, usu-
for the treatment of HTN. ally associated with concurrent upper respira-
tory infection (URI) or acute gastroenteritis.
Prognosis • Differential diagnosis: Postinfectious glomer-
• 90% recover completely. ulonephritis usually occurs 1–2 weeks after
infection.
• May also present as persistent microscopic
Denys-Drash Syndrome hematuria.
• Proteinuria is usually less than 1000 mg/24 h.
Background
• Rare: nephritic/nephrotic manifestation,
• Mutation in the Wilms tumor 1 gene (WT1)
facial edema, mild-to-moderate HTN, ele-
Clinical Presentation vated creatinine and BUN level (azotemia).
• Male pseudohermaphroditism with ambigu- • Negative serologies for viral infections or
ous external genitalia. autoimmune diseases, including normal com-
• There are three possible clinical/karyotype plement levels.
presentations: • Serum IgA level has no diagnostic value.
–– 46, XY with nephrotic syndrome, male • Diagnosis made by renal biopsy—indications
pseudohermaphroditism with ambiguous for biopsy: persistent proteinuria or micro-
external genitalia, and Wilms tumor scopic hematuria, elevated serum creatinine.
–– 46, XY with nephrotic syndrome and • Most children do not have progressive kidney
ambiguous external genitalia and/or inter- disease until adulthood, 15–20 years after
nal genitalia onset of the disease.
–– 46, XX with nephrotic syndrome and • Long-term follow-up is very important.
Wilms tumor
Poor Prognostic Factors
• Onset of proteinuria as early as at birth.
• Persistent HTN
• Steroid-resistant nephrotic syndrome.
• Abnormal renal function
Diagnosis • Persistent nephrotic-range proteinuria
• Renal biopsy shows diffused mesangial • Worst prognosis—renal biopsy shows dif-
sclerosis. fused mesangial proliferation, extensive glo-
merular crescent formation (proliferation of
Prognosis and Treatment the Bowman’s capsule epithelium), glomeru-
• Increased susceptibility to Wilms tumors losclerosis, tubulointerstitial changes such as
• Rapid progression to ESRD by age < 4 years atrophy and fibrosis
(may even occur in newborn period)
• No recurrence of disease in kidney transplant Treatment
• BP control.
• Alternate day of corticosteroids if the patient
IgA Nephropathy (Berger Disease) presents with overt nephritic syndrome with
nephrotic-range proteinuria.
Background • ACE inhibitors are effective in reducing pro-
• The most common chronic glomerular dis- teinuria, a combination of ACE inhibitors and
ease worldwide angiotensin receptor blockers (caution: need
• Peak incidence between 10 and 30 years of to check renal function frequently due to syn-
age, more common in Asians and Caucasians ergistic reduction in GFR).
810 B. Goilav
• Fish oil contains anti-inflammatory omega-3 Diagnosis

fatty acids and was thought to protect from • Careful family history
progression, but not evidence based. • Screening of first-degree female relatives
• Tonsillectomy not proven to reduce frequency (carriers)
of hematuria and renal disease progression. • Audiogram, ophthalmologic examination
(critical)
• Absence of GBM staining for alpha-3, and
Alport Syndrome alpha-4 of type IV collagen in male
hemizygotes
Background • Abnormal GBM architecture (basket
• 85% of cases are X-linked recessive—young weaving)
men, mutation in the COL4A5 gene.
• In the past, carriers of the genetic mutation Treatment and Prognosis
(i.e., the mothers of the male patients) were • Risk of progression to ESRD is highest in
believed to maintain normal renal function males affected by X-linked mode of inheri-
throughout life, but now there is evidence that tance and occurs in 75% before age 30 years.
they also progress to ESRD. Hence, carriers • Treatment is supportive and consists of con-
should be followed by a nephrologist as well. trol of proteinuria.
• Patients do well after kidney transplantation
Clinical Presentation but may develop anti-GBM disease (antibod-
• Single or recurrent gross hematuria may ies directed against normal GBM in the trans-
occur with URI (mostly in toddlers, young planted kidney) in ~15% of cases.
children), but most commonly persistent
microscopic hematuria (more than 2 years’
duration). Nail-Patella Syndrome
• Progressive proteinuria is common > 1 g/24 h
in the second decade of life. Background
• Extrarenal manifestations in X-linked reces- • Autosomal dominant
sive form. • Localized to chromosome 9, LMX1B gene
• Sensorineural hearing loss begins with high-
frequency range deficit. Clinical Presentation
• Ocular abnormalities: 30–40% of patients, • Hypoplasia or absence of the patella
anterior lenticonus (extrusion of the central • Dystrophic nails
portion of the lens into the anterior • Dysplasia of elbows and presence of iliac
chamber). horns
• Renal involvement in 30–40%:
Pathogenesis –– Microscopic hematuria
• Defect in collagen type IV, which is present –– Mild proteinuria
in the kidney, ear, and ocular lens
• Most commonly X-linked, but autosomal Diagnosis
recessive (mutation in the COL4A3 or • Renal biopsy reveals normal light micros-
COL4A4 gene) and dominant (mutation in copy and immunofluorescence staining, but
the COL4A3 or COL4A4 gene) forms on electron microscopy, GBM looks
described as well—female gender does not “moth-eaten.”
exclude diagnosis of Alport syndrome
23 Nephrology 811
Treatment Poor Prognostic Factor

• No specific therapy. • Type II histology (see Dense Deposit Disease)
• 10% of cases progress to ESRD.
ense Deposit Disease

D
Membranoproliferative (MPGN Type II)
Glomerulonephritis (MPGN)
Background
Background • Very rare
• There are three types; type I is the most • Poorly understood pathogenesis
common. • More aggressive disease than other types of
• Presence of crescents on biopsy is associated MPGN
with poor prognosis. • Possible abnormality in the complement coun-
ter-regulatory system (lack of inactivation of
Clinical Presentation the complement system) due to genetic defect,
• May present with asymptomatic proteinuria consumption, or inactivating antibodies
and hematuria, nephrotic syndrome, or an • Now also referred to as C3 glomerulonephritis
acute nephritic picture with gross
hematuria. Clinical Presentation
• Recurrent gross hematuria with intercurrent • Median age: 10 years old.
illness. • Clinically indistinguishable from other types
• Renal function may be normal or of MPGN.
diminished. • 50% present with nephrotic syndrome at
• HTN is common. onset.
• C3 level is persistently decreased in 75% • 30% have HTN at presentation.
of cases (at the time of presentation, con-
sider differential diagnosis: postinfectious Diagnosis
GN). • Biopsy.
• Generalized increase in mesangial cells and
Diagnosis matrix; capillary walls appear thickened, con-
• Biopsy. taining regions of duplication and splitting
• Presentation. (train tracks).
• Generalized increase in mesangial cells and • Complement abnormalities (low C3).
matrix; capillary walls appear thickened, con-
taining regions of duplication and splitting Prognosis and Treatment
(train tracks). • Poor prognosis
• Complement abnormalities (low C3). • No proven therapy; therefore, only supportive
care
Prognosis and Treatment • If there’s genetic defect in the complement
• 2 years of alternate-day steroids followed by system, plasmapheresis or plasma infusion
repeat biopsy. • Progression to ESRD in 10 years
• ACE inhibition to control proteinuria. • Recurrence of disease in kidney transplant.
• Some patients recover completely; 50% prog- Also known as immunec-mplex disease.
ress to ESRD. Similar to type I, but deposits are in subepi-
• C3 level never normalizes. thelial space.
812 B. Goilav
Lupus Nephritis (LN) Treatment

• Immunosuppression—be aggressive; if
Classification biopsy shows class IV LN, pulse methylpred-
• The International Society of Nephrology nisolone and cyclophosphamide or mycophe-
(ISN)/Renal Pathology Society (RPS) (for- nolate mofetil
merly WHO) groups LN into 6 classes and • Management of extrarenal manifestations
distinguishes between acute (A) and chronic • Sunscreen to protect from ultraviolet-induced
(C) lesions: disease flare
I. Minimal disease
II. Mild mesangial expansion and deposits Prognosis
III. Focal and segmental proliferation • Presence of anemia, azotemia, and HTN at
IV. Diffuse proliferation presentation is considered bad prognostic
V. Membranous factor.
VI. Fibrosis • A patient can change LN class, so it is not
• Class IV considered most aggressive, requir- unusual for patients requiring multiple biop-
ing most intense treatment. sies throughout the course of the disease—
• The National Institutes of Health (NIH) scor- immunosuppression may have to be adjusted
ing system informs about overall level of according to change in LN class.
acuity and chronicity, including the tubuloint-
erstitial compartment.
nti-glomerular Basement Disease
A
Clinical Presentation and Goodpasture Syndrome
• Typically, adolescent female with SLE:
–– 20% of SLE begins in childhood, and up to Background
60% of children with SLE have LN. • Antibody against specific epitopes of class IV
–– LN more aggressive in children and collagen in the glomerular/alveolar basement
patients of black ancestry. membrane
• Renal disease may precede serologies and • Isolated renal disease = anti-GBM disease
extrarenal manifestations of SLE. • Pulmonary involvement = Goodpasture
• Hematuria. syndrome
• Proteinuria.
• Reduced renal function (azotemia). Clinical Presentation
• HTN. • Rare in childhood.
• Extrarenal manifestations: anemia, arthritis, • Hemoptysis associated with pulmonary hem-
malar rash, serositis, cerebritis, abnormal orrhage can be life-threatening.
clotting/bleeding. • Acute nephritic syndrome with hematuria,
proteinuria, and HTN.
Diagnosis • Progressive renal dysfunction occurs within
• Serologies: positive ANA, anti-double-strand days to weeks.
DNA (dsDNA) antibodies
• Low C3 and C4 Diagnosis
• Autoantibodies against multiple self-antigens • Serum antibodies to GBM confirm the
(ribonucleoproteins) diagnosis.
• Definitive diagnosis on renal biopsy—also • On kidney biopsy, linear deposition of IgG
needed to guide therapy and C3 along the glomerular basement mem-
brane, crescent formation possible.
• Serum C3 is normal.
23 Nephrology 813
Prognosis and Treatment • Components of acid elimination:

• Recovery of renal function improved with –– Bicarbonate reclamation
steroids, cyclophosphamide, and –– Ammonium excretion
plasmapheresis –– Titratable acid excretion
Diagnosis
amilial Thin Basement Membrane
F • Normal anion gap (AG) metabolic acidosis.
Nephropathy • AG Na−(Cl+ HCO3) if < 12 means absence
of an AG.
Background • > 20 means no RTA.
• Isolated, nonprogressive hematuria with • Urine pH distinguishes proximal from distal
thinning of the glomerular basement types.
membrane • pH < 5.5 in the presence of acidosis suggests
• Autosomal dominant proximal RTA.
• Differential diagnosis—Alport syndrome, • pH > 6.0 in the presence of acidosis suggests
GBM having irregular structure distal RTA.
• Classically, patients present with failure to
Clinical Presentation thrive and repeated episodes of vomiting and
• Persistent microscopic hematuria. dehydration.
• RBC casts. • Patients appear ill; if they look well, yet have
• History may reveal another family member acidosis, they don’t have RTA!
with the same condition. • Workup:
• No family history of renal failure. 1. Determine AG.
• Proteinuria in up to 30% of adults. 2. Measure urinary AG: (UNa + UK)–UCl,
which is an indirect measurement of
Diagnosis ammonium and determines ability of the
• Biopsy reveals thin basement membrane on kidneys to respond to metabolic acidosis:
electron microscopy; light microscopy looks ◦◦ Approach is based on the fact that
normal. unmeasured cations and anions are con-
• Urinalysis and microscopy on affected first- stant and that ammonium would be the
degree family members. primary cation other than sodium or
potassium that would be excreted with
Treatment and Prognosis
chloride.
• No long-term complications, but if signifi-
3. Normal urine AG: zero or positive, with
cant proteinuria, may require ACE
metabolic acidosis. Urine AG: negative (−
inhibitor
20 to − 50), with RTA. Impaired ammo-
nium (excretion with chloride) results in
Na++ K+ > Cl−, so urine AG becomes zero
TUBULAR ABNORMALITIES or positive:
◦◦ Careful: Patients with diarrhea may have
Renal Tubular Acidosis (RTA)
a non-AG metabolic acidosis due to gas-
Background trointestinal (GI) losses of bicarbonate
• Net acid excretion = amount of acid elimi- (pancreatic fluid is bicarbonate rich), but
nated by the kidneys have a negative urine AG.
814 B. Goilav
• Approach to patient with hyperchloremic • Primary function of the distal nephron is acid-
metabolic acidosis: base homeostasis, which is to excrete acid
1. Measure urinary AG. generated from dietary intake.
2. If urinary AG negative—acidosis due to GI • In the growing child, excretion of 1–3 mmol
losses of bicarbonate. of acid per kg per day is needed.
3. If urinary AG positive—acidosis due to • Most pathophysiological consequences of dis-
renal bicarbonate loss or impaired urinary tal RTA are due to accumulation of acid—even
acidification. if the proximal tubule normally reabsorbs
bicarbonate, acid continues to accumulate,
resulting in increased base deficit.
Proximal RTA Type II • Once bicarbonate buffers in the extracellular
fluid are depleted, bones serve as buffer
• Threshold of bicarbonate reabsorption in the (hydroxyapatite is dissolved and hydroxyl
kidney is the main determinant of the serum ions serve to neutralize acid).
bicarbonate concentration. • Results in negative calcium balance and
• Hallmark of type II RTA = lowered threshold hypercalciuria with nephrocalcinosis and/or
for reabsorption of bicarbonate—threshold is nephrolithiasis.
usually 14–18 mEq/L and correlates with • Clinically distinct forms:
serum levels seen in these patients. –– Congenital distal RTA:
• Patients require large amounts of bicarbonate ◦◦ Autosomal dominant
(> 6 mEq/kg/day). ◦◦ Autosomal recessive with hearing loss
• Treatment with bicarbonate will increase uri- ◦◦ Autosomal recessive without hearing
nary pH due to increased excretion. loss
• Distal acid secretion is intact; hence, urine –– Acquired distal RTA:
pH can decrease to < 5. ◦◦ Immunologic destruction of
• Normal calcium excretion, no α-intercalated cells (Sjögren’s syn-
nephrocalcinosis. drome, SLE, Graves disease, medica-
tions [amphotericin B, lithium,
Clinical Symptoms melphalan, foscarnet])
• Polyuria
• Polydipsia
• Growth failure Type IV RTA
Seen in the Following Conditions (Some • Classic etiology: deficiency of or resistance
Examples) to effects of aldosterone on renal tubular
• Idiopathic Fanconi syndrome cells:
• Cystinosis –– Term applied to all forms of hyperkalemic
• Acute tubular necrosis RTA, regardless of serum aldosterone
concentration.
–– Aldosterone has direct effect on α-intercalated
Distal RTA Type I cells to promote proton secretion.
–– Acidosis in type IV RTA is not as severe as
• Hallmark = inability to lower urine pH maxi-
in other forms, but the main problem is
mally in the face of moderate-to-severe sys-
hyperkalemia.
temic acidosis.
–– Hyperkalemia can be life-threatening.
• Urine pH is always > 6.0.
23 Nephrology 815
• Most common inherited form of aldosterone Table 23.2 Difference between Bartter and Gitelman
deficiency is congenital adrenal hyperplasia. syndromes
• Aldosterone resistance is caused either by Features Bartter syndrome Gitelman syndrome
defects in the mineralocorticoid receptor or Age Prenatal, neonatal, and Late childhood,
early infancy adolescence, or
the epithelial sodium channel (ENaC)—both
adulthood
result in type IV RTA. Location of Ascending loop of Distal tubule
• Acquired forms of type IV RTA: defect Henle (mimic effects (mimic effects of
–– Most common—obstruction of the urinary of loop diuretics) thiazides)
tract (mechanisms not clear) Clinical Polyuria, polydipsia, Severe muscle
presentation vomiting, constipation, cramps, numbness,
salt craving, volume fatigue, recurrent
depletion episodes of
Bartter Syndrome dehydration
Blood Usually normal or low Lower than general
• Genetic defect (in this syndrome, multiple pressure if dehydrated populations
gene mutations can result in the same clinical Growth More common Less common
retardation
picture)
Metabolic Hypokalemic Hypokalemic
effect metabolic alkalosis metabolic alkalosis
Clinical Presentation Aldosterone High Usually normal
• History of polyhydramnios. and renin
• Dysmorphic feature. levels
• Hypokalemic metabolic alkalosis. Mg level Low in 30% Always low
Urine Ca Normal or high Low
• Hypercalciuria. (nephrocalcinosis)
• High level of renin, aldosterone, and prosta- Urine PGE High Normal
glandin E. PGE prostaglandin E
• Normal or low BP.
• Low serum Mg.
Treatment
• High level of urine Cl (patients with chronic
• Correction of hypokalemia and
vomiting have low urine Cl).
hypomagnesemia
Treatment • Vitamin K and Mg supplementation
• Prevention of dehydration.
• Correction of hypokalemia.
• Vitamin K supplements.
Cystinosis
• Indomethacin can be effective by inhibiting
Background
prostaglandin E.
• First treatable lysosomal storage disease
Etiology
Gitelman Syndrome (Table 23.2) • Autosomal recessive mutation in the CTNS
gene, which encodes cystinosin = protein that
• Hypokalemic metabolic alkalosis with hypo-
is responsible for transporting cystine out of
calciuria and hypomagnesemia
lysosomes
• Formation of cystine crystals within lyso-
Clinical Presentation somes due to the failure to transport cystine
• Recurrent muscle cramps and spasms out of the lysosomes
• Recurrent episodes of dehydration
816 B. Goilav
• Cystine = 2 molecules of cysteine joined by a Prognosis

disulfide bond • Without treatment, average age of death is
• Accumulation of cystine crystals in lyso- 28.5 years; patients are short, thin, blind, and
somes seen in electron microscopy unable to move, progressively lose vision and
ability to speak, and develop dementia.
Clinical Presentation • With treatment, normal life is expected, but
• Microscopic hematuria. they may still develop ESRD and require
• Hypothyroidism. transplant—no recurrence of disease in trans-
• Photophobia in young children should raise planted kidney.
suspicion—caused by crystal deposition in
the cornea (detectable as early as 16 months).
• Low to normal IQ. DIABETES INSIPIDUS (DI; SEE
• Fanconi syndrome (proximal tubular defect) CHAPTER 12 ENDOCRINOLOGY
with metabolic acidosis, phosphaturia, pro-
teinuria, and glucosuria. FOR CENTRAL-TYPE DI)
• Craving salt (due to proximal tubular loss of
sodium). Nephrogenic Diabetes Insipidus
(NDI)
Diagnosis
• Multiple organs involved: cornea, conjunc- Background
tiva, liver, spleen, kidneys, intestines, rectal • Definition: insensitivity of the distal nephron
mucosa, pancreas, testes, lymph nodes, bone to the antidiuretic effects of the neurohypo-
marrow, macrophages, thyroid, skeletal mus- physial hormone, arginine vasopressin
cle, and choroid plexus.
• Renal biopsy scan shows crystals in tubular Etiology
cells—birefringent hexagonal or rectangular • Primary form presents with three different
crystals, but clinical suspicion required first, inheritance patterns:
because tissue has to be processed in a special –– 90% X-linked recessive—vasopressin 2
way to preserve the crystals. receptor mutation
• Genetic testing offers definitive diagnosis. –– Autosomal recessive—aquaporin 2 mutation
–– Autosomal dominant—aquaporin 2 mutation
Treatment • Secondary form can be seen due to nephro-
• Oral cysteamine treatment—difficult to main- toxic drugs, chronic pyelonephritis, obstruc-
tain compliance, because medication that tive uropathy, sickle cell trait, etc.
smells like rotten eggs and tastes terrible has
to be taken four times a day; new formulation Clinical Presentation
somewhat improved due to decreased fre- • Normal birth weight, no polyhydramnios.
quency of administration • Urine concentrating defect present at birth,
• Replacement of renal losses but breastfed infants thrive because breast
• Thyroxine milk has low renal osmolar load, decreasing
• Recombinant human growth hormone risk of dehydration—diagnosis delayed.
administration • Constipation is a common symptom.
• Dialysis, kidney transplantation • Failure to thrive if remains unrecognized
later, but bone age not delayed.
23 Nephrology 817
• May develop intellectual disability if Incidence

untreated due to central nervous system calci- • 1:20,000 live births
fications after hemorrhage or necrosis.
• Many NDI patients are characterized as Clinical Presentation
hyperactive, distractible, restless, and with • May be associated with oligohydramnios,
short attention span. pulmonary hypoplasia, respiratory distress,
and spontaneous pneumothorax in the neona-
Diagnosis tal period.
• History of inability to toilet train, frequent • Potter facies and other components of the oli-
daytime accidents due to polyuria. gohydramnios complex, low-set ears, micro-
• Constant thirst—children would rather just gnathia, flattened nose, limb position defects,
drink than eat. and growth deficiency.
• First morning urine SG is < 1.015 (specimen • Bilateral flank mass during the neonatal
obtained when the child wakes up in the period or early infancy.
morning). • HTN is usually noted within the first few
• Hypernatremia with polyuria. weeks of life.
• Vasopressin test: vasopressin given intrana- • Urine output is usually not diminished.
sally and urine collected before and there- • Transient hyponatremia often with AKI.
after—urine osmolality remains • Renal function is usually impaired but may
< 200 mOsm/L. initially be normal in 20–30% of cases.
• Plasma antidiuretic hormone levels normal or • Ascending cholangitis.
high. • Hypersplenism related to portal HTN
• Renal and bladder ultrasound shows a large • Progressive liver dysfunction
bladder with a trabeculated wall, hydroure-
ters, and hydronephrosis. Diagnosis
• Voiding studies show large-capacity hypo- • Renal ultrasound
tonic bladder dysfunction. • Hyperechogenic kidneys with poor cortico-
medullary differentiation
Treatment • Genetic testing
• Low solute diet—restrict sodium and • Signs of hepatic fibrosis and/or portal HTN
protein
• Thiazide diuretics (less salt delivered to the Treatment
distal nephron results in less water loss) • Supportive
• Indomethacin (decreases GFR; hence, less
sodium and water enter the nephron and can Prognosis
be lost) • 30% of patients die in the neonatal period
from pulmonary hypoplasia.
• If the patient survives the neonatal period,
CYSTIC KIDNEY DISEASES excellent prognosis, but will require kidney +
/− liver transplant.
Autosomal Recessive Polycystic • ESRD is seen in > 50% of cases.
• Dialysis and transplant become the standard
Kidney Disease (ARPKD)
of therapy.
• Infantile polycystic disease
• Mutation in the PKHD1 gene encoding fibro-
cystin/polyductin
818 B. Goilav
utosomal Dominant Polycystic

A • Variability of disease within families with
Kidney Disease (ADPKD) the same mutation (poor genotype-phenotype
correlation).
• 85% of patients have the PKD1 gene encod- • Women with PKD2 mutation have the most
ing polycystin-1. favorable outcome, but still progress.
• 10 to 15% of patients have the PKD2 gene
encoding polycystin-2.
• While autosomal dominant mode of inheri- N ephronophthisis (NPH)
tance is the most common, spontaneous muta-
Background
tions are relatively frequent.
• Most common type (25%) is juvenile nephro-
nophthisis type I (mutation in the NPHP1 gene).
Incidence
• 1:500—most common monogenic disease! Clinical Presentation
• Polyuria
• Polydipsia
• ADPKD presents most commonly in adult
• Anemia due to erythropoietin deficiency (out
life, but cysts can already be seen in utero (no
of proportion to degree of kidney failure)
impact on disease progression).
• Gross hematuria, bilateral flank masses,
• Extrarenal features (Joubert syndrome):
HTN, and urinary tract infection.
–– Ocular motor apraxia (inability to perform
• ADPKD is a systemic disease and affects
the horizontal eye movement)
many organs, e.g., liver, pancreas, spleen, and
–– Retinitis pigmentosa
ovaries; intracranial aneurysm appears in
–– Coloboma of the eye
clusters within certain families.
–– Cerebellar vermis aplasia with broad-based
• Mitral valve prolapse in 12% of cases.
gait
Diagnosis
Diagnosis
• Ultrasound, multiple bilateral macrocysts.
• Renal ultrasound shows loss of corticomedul-
• Absence of family history does not preclude
lary differentiation.
this diagnosis.
• Renal biopsy shows cystic dilation of medul-
• Neonatal ADPKD and ARPKD may be
lary collecting tubules.
indistinguishable.
Prognosis
Treatment
• ESRD occurs on average by age 13 years.
• Supportive.
• Only aggressive BP control has been proven
to slow down disease progression aurence-Moon-Bardet-Biedl
L
• Vasopressin-2 receptor inhibitors have shown Syndrome
to slow cyst growth, but no data is available
on clinical outcome. Background
Prognosis
• Progression to ESRD in the fifth to sixth Clinical Presentation
decade. • Obesity
• Retinitis pigmentosa
23 Nephrology 819
• Hypogonadism Prognosis
• Polydactyly • Favorable, normal life expectancy.
• Mental deficiency • Patient needs to avoid contact sports to pre-
• Cystic dysplasia of the kidneys vent injury and trauma to the solitary kidney.
Treatment
• Supportive
RENAL FAILURE
Prognosis
• Progression to ESRD in late adolescence/ A cute Kidney Injury (AKI) [3, 4]
early adulthood, requiring dialysis/kidney
transplantation Definition
• Sudden decline in renal function
• Increase in BUN and serum creatinine
Multicystic Dysplastic Kidney values
Disease • +/− Hyperkalemia
• +/− Metabolic acidosis
Background
• +/− HTN
• Not the same as polycystic kidney disease
• Not a monogenic disorder Prerenal AKI
Clinical Presentation Definition
• Unilateral abdominal mass of the newborn. • Hypoperfusion of the kidneys
• Bilateral multicystic dysplasia results in fetal
demise. Causes (Most Common)
• Effectively, the patient has only one function- • Hypovolemia due to GI diseases
ing kidney. • Congenital heart disease
• Sepsis
Diagnosis
• Usually diagnosed on prenatal ultrasound. Diagnosis
• Need to do voiding cystourethrogram • Clinical history should reveal causes of vol-
(VCUG) to rule out contralateral vesico- ume depletion, such as the following:
ureteral reflux, which is commonly encoun- –– Dehydration due to vomiting or
tered (30–50%). gastroenteritis
• Expectation is that the dysplastic kidney –– Hemorrhage
involutes over time. –– Cardiac failure, or third-space fluid losses
• Stable size is acceptable, but if the dysplastic
kidney grows, referral to urology for nephrec- Laboratory Findings
tomy is indicated because the dysplastic kid- • Decreased urine output.
ney contains immature cells, which may • Normal urinary sediments.
undergo malignant transformation. • Increased urine osmolality (> 400.0 mOsm in
the older child and > 350.0 mOsm in the
Treatment neonate).
• Serial renal ultrasounds to ensure involution • Low urinary sodium (< 10.0 mEq/L
or stable size of the dysplastic kidney [10.0 mmol/L]).
• Parental reassurance that the solitary func- • Low fractional excretion of sodium (< 1% in
tioning kidney is compatible with life the older child and < 2.5% in the newborn).
820 B. Goilav
• Increased BUN-to-creatinine ratio. • A low complement C3 value may indicate an

• Renal ultrasonography and renal scan find- underlying diagnosis of SLE and membrano-
ings should be normal. proliferative or poststreptococcal
glomerulonephritis.
Renal or Intrinsic Renal Failure • For a patient with a high suspicion of glomer-
ulonephritis, a biopsy may be warranted if the
Definition patient has, in addition to gross hematuria
• Parenchymal injury due to vascular spasm, and proteinuria, rapidly rising BUN and cre-
intravascular coagulation, and microvascular atinine serum values (= RPGN).
injury • Low urine osmolality (< 350.0 mOsm).
• Large muddy-brown granular casts.
The Most Common Causes
• High urinary fractional excretion of sodium
• Acute tubular necrosis, e.g., rhabdomyolysis
(> 2% in the older child and > 2.5–3% in the
secondary to dehydration
newborn); renal scans can be helpful in diag-
• Interstitial nephritis
nosis because they can demonstrate whether
• Hemolytic-uremic syndrome, e.g., history of
the renal cortex is perfused or if there is corti-
diarrhea
cal necrosis with little chance of a return of the
• Glomerulonephritis, e.g., prosthetic valve
renal function back to baseline, as well as
causing endocarditis, streptococcal
the differential function between the left and
pharyngitis
the right kidney (e.g., one kidney has lost all of
• Nephrotoxic drugs, e.g., cystic fibrosis patient
its function and the other is compensating).
receiving aminoglycosides
• If necessary, a renal biopsy is the next step in
Diagnosis determining the cause of intrinsic renal
• Clinical history may reveal as follows: failure.
–– Dehydration
General Indicators for Renal Biopsy
–– Hypoxic-ischemic events
• Rapidly increasing serum creatinine
–– Toxic ingestion, nonsteroidal anti-
concentration
inflammatory drugs (NSAIDs), or other
• To establish a diagnosis of acute vs. chronic
nephrotoxic medication uses
glomerulonephritis
–– Signs and symptoms of sepsis, gross hema-
• Positive serology for systemic diseases such
turia, or trauma
as MPGN or SLE and azotemia with urinary
• Decreased urine output can be described as
findings of hematuria or proteinuria
oliguria (< 0.5 mL/kg per hour in a child or
• To demonstrate an active lesion in which
< 1 mL/kg per hour in an infant) or as anuria
immunosuppressive medications, such as ste-
(no urine output).
roids, may help to reverse the disease process
Laboratory Finding and recover renal function
• RBC casts, granular casts, and RBCs—find-
ings seen in glomerulonephritis.
• Studies should include streptococcal antibod-
cute Interstitial Nephritis (AIN)
A
ies, hepatitis B and C panels, and comple-
Background
ment studies.
• Tubulointerstitial compartment makes up
• Streptococcal antibodies, including the anti-
80% of the renal parenchyma.
streptolysin O titer, anti-DNAse B titer, and
• AIN is a cause of acute kidney injury (AKI)
group A antibody to Streptococcus pyogenes
in childhood in up to 7% of cases.
titer, should be obtained.
23 Nephrology 821
Clinical Presentation • Rarely, chronic interstitial nephritis occurs

• Nonspecific due to chronic drug use or chronic obstructive
• Fatigue due to anemia (erythropoietin is pro- uropathy; progresses to ESRD.
duced in the interstitium)
• Usually unexpected finding of elevated serum
BUN and creatinine
• 30 to 40% non-oliguric AKI cute Tubular Necrosis (ATN)
A
• Rarely systemic symptoms of allergic reac-
Background
tion (rash, joint pain), eosinophilia
• Hypoperfusion of the kidneys leading to
• Urine sediment usually bland with some
reversible damage of the proximal tubule
WBCs
Etiology
Diagnosis
• Hemorrhage
• History of medications:
• Severe volume depletion
–– Most commonly antibiotics, among which
• Sepsis with decreased effective blood volume
penicillins are most common
(third spacing)
–– NSAIDs
–– Any other medications Diagnosis
• Infections • Oligoanuria
• Autoimmune diseases (SLE, tubulointersti- • Elevated serum creatinine and BUN, muddy-
tial nephritis with anterior uveitis [TINU]) brown casts in urine
• Urine eosinophils (identified by Wright stain)
pathognomonic for allergic AIN, but absence Treatment
does not exclude AIN • Normal saline for volume replacement
• Urinalysis usually quite bland, low SG due to
concentrating defect (damage to the Management of Renal Failure
tubulointerstitium) • Maintaining renal perfusion
• Biopsy usually not indicated due to clinical • Fluid and electrolyte balance
constellation making other diagnoses unlikely • BP control
• Adequate nutrition
Prognosis and Treatment • Adjust medications to decrease GFR
• Generally, self-resolving, monophasic illness • Initiate renal replacement therapy (early
(i.e., once serum creatinine plateaus, it should dialysis)
improve later; if not, then look for other
causes of AKI).
• Most patients have mild, vague symptoms, Hemolytic Uremic Syndrome (HUS)
but if the patient feels ill or if serum creati-
nine rises at significant speed, obtain renal Etiology
biopsy for exclusion of rapidly progressive • Typical HUS = diarrhea-associated HUS:
GN, followed by short course of high-dose –– Shiga toxin-producing E. Coli 0157:H7
steroids (2 mg/kg, max. 60 mg/d, 5 days, then (causative agent in 80% or more in devel-
taper; or methylprednisolone 1 g daily for oping countries)
3 days). –– S. pneumoniae
• Atypical HUS = (genetic) abnormality of
complement regulatory pathways:
822 B. Goilav
–– Any organism can trigger the disease. • Meticulous attention to fluids and electro-
–– Usually in younger patients. lytes, control of HTN, and early dialysis.
• Age: • Antibiotics are contraindicated for treatment
–– More common in children 2–5 years of age of diarrhea if E. coli 0157 is suspected.
• Atypical HUS is caused by a defect in the
Clinical Presentation for Typical HUS complement regulatory system and requires
• Onset preceded by acute gastroenteritis or blockade of the complement system with an
pneumonia antibody that binds to C5 (eculizumab),
• Fever thereby inhibiting its activation.
• Vomiting
• Abdominal pain Prognosis
• Watery diarrhea which then becomes bloody • Disease is monophasic; once the patient
• Dehydration recovers, no relapse should occur in typical
• Edema HUS. Any deviation from this clinical course
• Petechiae is suggestive of atypical HUS, and plasma-
• Hepatosplenomegaly pheresis should be initiated immediately
• HTN, pallor, lethargy pending genetic testing.
• Patients recovering from typical HUS require
Clinical Presentation for Atypical HUS long-term follow-up because of complica-
• Patient may be < 6 months. tions such as HTN and chronic kidney
• No GI symptoms. disease.
• Insidious onset with lethargy, pallor, and • Patients with atypical HUS and confirmed
feeding difficulties. genetic defect in the counter-regulatory com-
• Severe HTN. plement system require treatment with an
• Possible family history. inhibitor of the C5 component, which is most
likely lifelong. This treatment leads to inabil-
Diagnosis ity of the patient to clear infections with
• Triad consisting of the following: encapsulated organisms; hence, prior vacci-
–– Microangiopathic hemolytic anemia nation is imperative.
–– Thrombocytopenia
–– AKI
• Peripheral smear: schistocytes, burr cells, or MISCELLANEOUS
helmet cells.
• Hemoglobin level in the 5–9 g/dl range. (Nocturnal) Enuresis [5]
• Leukocytosis may exceed 30,000 (associated
with worse prognosis for renal recovery). Background
• Thrombocytopenia in 90% of cases. • 90 to 95% of children are nearly completely
• Elevated BUN/creatinine with oligoanuria. continent during the day, and 80–85% are
• Microscopic hematuria and proteinuria. continent during the night after the age of
• Prothrombin time (PT) and partial thrombo- 6 years for girls and 8 years for boys.
plastin time (PTT) are usually normal. • More common in boys (60%).
• Family history (50%).
Treatment • If one parent was enuretic, there’s 44% a chance
• Supportive. of enuresis in the child; and if both parents
23 Nephrology 823
were enuretic, 77%; age at resolution in parents • Also, patient may present with microscopic
can guide expectations of resolution in child. hematuria, flank pain, HTN, or oliguria.
• Bilateral RVT results in AKI.
• Primary or secondary enuresis Diagnosis
• History of voiding dysfunction manifested as • Hematuria, flank masses in a patient with pre-
holding urine and often combined with disposing clinical factors.
constipation • Ultrasound shows marked enlargement, and
• Diabetes mellitus and insipidus (urinalysis on Doppler ultrasound will confirm diagnosis.
the first morning urine sample is helpful—if Treatment
SG is < 1.015, it is suspicious for DI; pres- • Supportive, hydration
ence of glucose requires workup for DM).
Treatment
Sickle Cell Nephropathy
• Reassurance of parents.
• Exclude any type of voiding dysfunction dur- Background
ing the daytime, as this may be the cause of • Consequences related to sickling and anemia
the nocturnal enuresis (prolonged withhold- = “renal sickle cell crisis”
ing of urine).
• Fluid restriction in the evening is moderately Clinical Presentation
successful. • Hematuria and renal papillary necrosis:
• Acute treatment should be avoided before the –– Painless gross hematuria
age of 6 years. –– More frequent with sickle cell trait
• Motivational therapy. –– Occurs due to low oxygen tension in the renal
• Conditioning therapy (vibratory alarm) cura- papilla causing local sickling and thrombosis
tive in 30–60%. within the vasa recta of papilla, leading to
• Desmopressin: progressive destruction of the papilla and
–– Well tolerated and has very few reported secondary deposition of calcium—echogenic
adverse effects. papillae on renal ultrasound
–– Severe hyponatremia associated with sei- • Proteinuria with sickle cell glomerulopathy
zures and deaths has been reported and
occurs only due to water intake after drug Diagnosis
is taken at night. • Renal ultrasound
• History of sickle cell disease or trait
• Urinary concentrating defect = low urine SG
Renal Vein Thrombosis (RVT) in the setting of dehydration
Etiology Treatment
• Neonatal asphyxia, dehydration, shock or • Supportive
sepsis, congenital hypercoagulable states, • ACE inhibitors in case of proteinuria
infant born to a mother with DM
Prognosis
Clinical Presentation • Secondary to chronic anemia; patients with
• Sudden onset of gross hematuria and unilat- sickle cell disease may develop FSGS with
eral or bilateral flank masses. progression to ESRD.
824 B. Goilav
PEARLS AND PITFALLS • Any child with edema and HTN presenting to

the emergency department should be admit-
• Transient proteinuria in children is common, ted for further workup and observation.
and attention should be paid to the concentra- • Clinical and serological markers of lupus
tion of the urine sample when interpreting it. nephritis, such as proteinuria, hematuria,
• A first morning urine sample should be HTN, hypocomplementemia, and elevated
obtained first before referral of the patient. anti-dsDNA antibody titers, do not correlate
• It is important to distinguish between painful with class or severity of renal involvement in
and painless gross hematuria. SLE.
• Painful hematuria is more likely to be lower
tract than glomerular. Acknowledgment Dr. Goilav would like to thank
• Painless hematuria may be either glomerular Dr. Casimir Cohen for his invaluable advice in the
or lower tract hematuria. writing of this chapter.
• Asymptomatic hematuria persisting for
> 2 years warrants referral to a specialist for
renal biopsy. References and Suggested Reading
• Kidney stones in children under the age of
12 years warrant genetic workup. 1. Bushinsky DA, Coe FS, Moe OW. Nephrolithiasis.
• In 2017, the guidelines for the diagnosis of In: Brenner BK, editor. Brenner & Rector’s the
HTN in children have been changed, includ- kidney, vol. 2. 8th ed. Philadelphia: Saunders;
ing changes in terminology, with “prehyper- 2008. p. 1299–349.
tension” being replaced by “elevated BP”; 2. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey
new normative pediatric BP tables based on D, Carroll AE, Daniels SR, Subcommittee on
non-overweight and non-obese children; and Screening and Management of High Blood
a simplified classification in adolescents Pressure in Children, et al. Clinical practice
≥ 13 years of age. The overall normal BP lim- guideline for screening and management of
its are now lower in children. high blood pressure in children and adolescents.
• A urinalysis that contains both protein and Pediatrics. 2017;140(3):e20171904.
blood may be suggestive of nephritis, and fur- 3. Andreoli SP. Acute renal failure. Curr Opin
ther evaluation is warranted. Pediatr. 2002;14(2):183–8.
• Patients with nephritis may present with edema 4. Goldstein SL. Pediatric acute kidney injury:
and nephrotic-range proteinuria, but they dis- it’s time for real progress. Pediatr Nephrol.
tinguish themselves from patients with 2006;21(7):891–5.
nephrotic syndrome by displaying elevated BP 5. Cooper CS. Voiding dysfunction. eMedicine
and a rise in serum creatinine from baseline. Drugs Dis Pediatr: Surg. 2017. http://emedi-
cine.medscape.com/article/1016198-overview.
Accessed 24 Feb 2019.
Fluids and Electrolytes
24
Benjamin Steinman and Beatrice Goilav
GENERAL Fluid Compartments
Body Fluid Composition

Osmolality
• ECF and ICF volumes are maintained due to
• Total body water (TBW) is 75% of body osmotic equilibrium
weight in term infants • Normal plasma osmolality = 285–
• TBW decreases to 60% of body weight until 295 mOsm/kg. Typically, equivalent to ICF
puberty, then males 60%, females 50% (due osmolality
to increased adipose tissue) • Calculated plasma osmolality = (Na × 2) +
• TBW is divided into extracellular fluid (ECF) Glucose/18 + BUN/2.8
and intracellular fluid (ICF): • Note: Urea typically an ineffective osmole
–– ICF is 40% of body weight except in very high concentrations, e.g.,
–– ECF is 20% of body weight. ECF is divided inborn errors of metabolism (IEM) and liver
into: failure
◦◦ Interstitial fluid (15%) and plasma (5%) • Calculated osmolality is typically equivalent
of body weight, respectively to measured osmolality
• (Tip: 60–40–20 to remember % TBW) • It is useful to obtain measured osmolality in
• Example: 20 kg child: suspected toxic alcohol ingestion (see
–– TBW = 12 L (60%) Metabolic Acidosis)
–– ICF = 8 L (40%) –– Toxic alcohol ingestion causes increase in
–– ECF = 4 L (20%): osmolar gap > 10 between measured and
◦◦ Interstitial fluid = 3 L (15%), calculated osmolality
plasma = 1 L (5%) • Osmolality can be affected by hyperglyce-
mia, hyperlipidemia, and hyperproteinemia
(see Hyponatremia)
Osmotic equilibrium
• Osmotic equilibrium is maintained since cells
B. Steinman
Department of Pediatrics, The Children’s Hospital at SUNY are permeable to water
Downstate, SUNY Downstate Medical Center, • Osmotic equilibrium is further regulated by
Brooklyn, NY, USA
antidiuretic hormone (ADH):
B. Goilav (*)
Pediatric Nephrology, Children’s Hospital at Montefiore,
–– Elevated osmolality causes increased ADH
Albert Einstein College of Medicine, Bronx, NY, USA secretion, which leads to increased water
e-mail: bgoilav@montefiore.org

826 B. Steinman and B. Goilav
reabsorption to bring osmolality back to • Hyperosmotic contraction will increase

equilibrium osmolality in ECF and decrease volume of
–– ADH is sensitive to osmolality changes of both compartments, e.g.:
< 1% –– Diabetes insipidus (DI) (dilute urine),
excessive sweating
Fluid Changes Hypoosmotic

• Hypoosmotic expansion will decrease osmo-
• The gain or loss of fluid primarily affects lality in ECF and expand both compartments,
ECF in early stages of dehydration e.g.:
• Fluid changes can be isosmotic, hyperos- –– Water intoxication, syndrome of inappro-
motic, or hypoosmotic (Table 24.1) priate antidiuretic hormone secretion
(SIADH)
Isosmotic • Hypoosmotic contraction will decrease
• Expansion/contraction of isosmotic fluid to osmolality in ECF, and water will be drawn
ECF will increase/decrease ECF volume into ICF, expanding ICF and decreasing ECF
without changes to ICF, e.g., volume, e.g.:
–– Expansion: Normal saline infusion –– Adrenal insufficiency (concentrated urine)
–– Contraction: Secretory diarrhea • Third spacing, i.e., changes in interstitial
fluid/edema, e.g.:
Hyperosmotic
–– Heart failure, protein-losing enteropathy,
• Hyperosmotic expansion will increase osmolal-
liver failure, nephrotic syndrome, and
ity in ECF and will draw water into ECF, expand-
sepsis
ing ECF and decreasing ICF volume, e.g.:
–– Hypertonic saline, glucose infusion, dia-
betic ketoacidosis (DKA)
SODIUM (NA)
Table 24.1 Fluid compartment changes
Background
Changes Changes Changes Changes
• Requirements: 2–4 mEq of Na+/100 mL. May
to ECF to ICF to ECF to ICF
Fluid changes volume volume osmolality osmolality be slightly more in term newborn due to natri-
Volume expansion uresis after 2–3 days of life
Hypoosmotic Increase Increase Decrease Decrease • Na+ is the primary ECF cation and the main
(SIADH, determinant of osmolality
water • Changes in serum sodium are typically
intoxication)
Hyperosmotic Increase Decrease Increase Increase affected by water gain or loss, not sodium
Isosmotic Increase No No change No change gain or losses. This can be appreciated when
change determining the causes of hyper- and
Volume contraction hyponatremia
Hypoosmotic Decrease Increase Decrease Decrease
Hyperosmotic Decrease Decrease Increase Increase
Isosmotic Decrease No No change No change
change Hypernatremia
ECF extracellular fluid (ECF), ICF intracellular fluid,
SIADH syndrome of inappropriate antidiuretic hormone
Definition
secretion • Serum Na+ > 150 mEq/L
24 Fluids and Electrolytes 827
Causes ▪▪ Primary hyperaldosteronism, Cushing

• Water deficit (e.g., decreased feeds, concen- syndrome, hypertonic saline
trated formula, premature infants, DI)
• Excessive sodium intake (e.g., excess for- Treatment (Tables. 24.2 and 24.3)
mula, hypertonic saline, hyperaldosteronism) • Bolus with 0.9% normal saline (NS) if signs
• Combined sodium and water losses (e.g., of vascular compromise are present
diarrhea/vomiting with inadequate intake, –– Maintenance fluids and electrolytes: See
phototherapy, burns, fever, diabetes mellitus, Maintenance Fluid Requirements
diuretics, obstructive uropathy) • Fluid deficit
–– The fluid deficit in a patient with hyperna-
Signs and symptoms tremia is composed of two parts:
• Irritability, weakness, and lethargy. Infants ◦◦ Free water deficit: The additional free
may have a high-pitched cry and tachypnea. water that the patient needs to correct his
Skin will often have a doughy consistency hypernatremia
• Hypernatremic dehydration is initially well ▪▪ Free water deficit = [(Serum Na+/140)
tolerated, since fluid shifts from the ICF to − 1] × 0.6 × weight (kg)
the ECF, which maintains intravascular vol- ◦◦ Solute water deficit: The remaining
ume. This causes delay in diagnosis; patients fluid deficit, which is lost from ECF
look well and the level of dehydration is and ICF with corresponding electrolyte
underestimated deficits
• Hypernatremia can also cause hyperglycemia ▪▪ Solute water deficit (aka solute fluid
and hypocalcemia deficit or SFD [L]) = Total water defi-
• Lab findings of prerenal azotemia include: cit − free water deficit
–– Fractional excretion of sodium (FeNa) • Electrolyte deficits
< 1% and blood urea nitrogen creatinine –– Solute Na+ deficit = SFD (L) × proportion
(BUN/Cr) ratio > 20:1 from ECF × 140 mEq/L or replace 8 mEq
Na+/100 mL water lost
Diagnosis (Fig. 24.1) –– Solute K+ deficit = SFD (L) × proportion
• Assess volume status from ICF × 160 mEq/L or replace 6 mEq
–– Hypovolemia: TBW loss > Na+ loss K+/100 mL water lost
◦◦ Renal (diuretics, renal disease) • Slowly correct the serum sodium and fluid
◦◦ Extrarenal (sweating, diarrhea, burns, deficit over 48 h.
phototherapy) • Free water deficit replaced over 48 h (see
◦◦ Urinary Na+ will be > 20 mEq/L in renal Complications below)
losses • Consider replacing free water deficit even
–– Euvolemia: Decrease in TBW, no increase more slowly for severe hypernatremia
in Na+ • Do not correct > 12 mEq/24 h or 0.5 mEq/h
◦◦ Renal losses: DI, hypodipsia • Do not use Ringer’s lactate solution, as it is
◦◦ Extrarenal: Insensible losses hypotonic
◦◦ Urinary osmolality will be < 290 mOsm/
kg in DI. Complications
–– Hypervolemia: Increased Na+> increased • Cerebral hemorrhage occurs if hypernatremia
TBW is left untreated due to increased ECF osmo-
◦◦ Think salt gain; urinary Na is increased.
+
lality, which causes fluid to shift from ICF
Hypernatremia
Volume status?
Hypovolemia: Euvolemia: Hypervolemia:

Significantly decreased TBW Decreased TBW Decreased TBW
Decreased Na Normal Na Increased Na
Renal losses:
Central and nephrogenic Extrarenal losses:
Urinary Na > 20mEq Urinary Na< 20mEq Urinary Na > 20mEq
diabetes insipidus Insensible losses
Hypodipsia
Renal losses:
Osmotic diuresis Primary hyperaldosteronism,
Extrarenal Losses:
(glucosuria, mannitol), Cushing syndrome,
Sweating, diarrhea, burns,
loop diuretics, postobstruction, nasogastric secretions hypertonic dialysis,
renal disease (ATN) NaCl tablets
Hypertonic bicarb
Viral gasteoneteritis
Hypertonic formula
Treatment: 1) Maintenance
Fluid + electrolytes 2) Free
water Deficit 3) Solute Deficit +
electrolytes 4) Subtract boluses
Fig. 24.1 Hypernatremia workup
Table 24.2 Calculation of intravenous rehydration in cases of hypernatremia

Water requirements Sodium requirements Potassium requirements
Maintenance × 48 h Maintenance fluid requirements × 2 3 mEq/100 mL 2 mEq/100 mL
Fluid deficit 1 mL: 1 g of weight lost – –
Free water deficit [(Serum Na+ /140) − 1] × 0.6 × weight (kg) – –
Solute deficit Fluid deficit – free water deficit 8 mEq/100 mL 6 mEq/100 mL
Bolus – – –
Total – – –
and decreased brain volume. This can lead to • Rapid correction can cause cerebral cellular
tearing of bridging blood vessels swelling and seizures since idiogenic osmoles
• Seizures can occur, but they are more com- are produced in the ICF with long-standing
mon during correction hypernatremia. This will cause fluid to shift
Table 24.3 An example of how to calculate and how to order intravenous fluid (IVF) in cases of hypernatremic
dehydration
A 20 kg child with Na+ 160 and 10% dehydration who received 20 cc/kg 0.9% normal saline bolus × 1
Maintenance × 48 h Maintenance fluid requirements × 2 3000 mL/100 mL = 30 3000 mL/100 mL = 30
Weight of 20 kg = 3000 mL 30 × 3 mEq = 90 mEq/24 h 30 × 2 mEq = 60 mEq/24 h
90 × 2 = 180 mEq/48 h 60 × 2 = 120 mEq/48 h
Fluid deficit 20 kg × 0.1 = 2 kg = 2000 mL – –
Free water deficit 160/140 = 1.14 – –
1.14 − 1 = 0.14
0.14 × [0.6 × 20] = 1680 mL
Solute deficit 2000 –1680 mL = 320 mL 320/100 = 3.2 320/100 = 2.86
3.2 × 8 = 25.6 mEq 3.2 × 6 = 19.2
Bolus −400 mL −61.6 mEq –
Total 4600 mL 144 mEq 139.2 mEq
Fluid rate: 4600/48 h = 95 mL/h
to ICF during correction. Therefore, correct ◦◦ Hypertriglyceridemia

free water deficit over 48 h ◦◦ Hypercholesterolemia
◦◦ Intravenous immunoglobulin (IVIG)
–– Elevated osmolality
Hyponatremia ◦◦ Hyperglycemia
◦◦ Mannitol infusion
Definition –– To correct for hyperglycemia: Add 1.6 Na+
• Na < 130 mEq/L for every 100 mg/dL of glucose over
• If TBW loss is present, losses are entirely 100 mg/dL
from ECF, and shift into ICF can cause over- • Hypo-osmolar: Assess volume status
estimation of dehydration. However, patients • Hypovolemic hyponatremia: Na+ losses
may also be intravascularly depleted and > water losses
require fluid resuscitation –– Extrarenal: Hypotonic fluid or replace-
ment (e.g., diluting formula) in diarrheal
Diagnosis (Fig. 24.2)
states (the most common cause), vomiting,
Etiology and dehydration. ADH is also stimulated
• Diarrhea and diuretics are the most common by volume loss, exacerbating hyponatre-
causes mia. This form of dehydration is also seen
in cystic fibrosis and hypoaldosteronism
Check serum osmolality: –– Renal: Diuretics, ACE inhibitors, miner-
• Isosmolar, i.e., pseudohyponatremia: hyper- alocorticoid deficiency
lipidemia, hyperproteinemia –– Urine Na+ > 20 mEq/L in renal losses
–– Total body sodium stores are normal –– Third space losses are isosmotic, but ADH
• Hyperosmolar, i.e., dilutional hyponatremia secretion can cause hyponatremia. Can be
without symptoms of hyponatremia since it is seen with diuretics
the change in osmolality that produces symp- –– Urea is effective osmole in cases where it
toms, not sodium in and of itself accumulates (renal failure, IEM). In such
–– Normal osmolality: instances, patients can have normal osmo-
Hyponatremia
Assess serum
osmolality
Isotonic (285-295 Hypotonic: Hypertonic:

mOsm/kg)
Pseudohyponatremia Assess volume Hyperglycemia, Mannitol,

hyperlipidemia, status: Hypertriglyceridemia
hyperproteinemia
Euvolemic:
Urine Hypervolemic
Na > 20mEq Hypovolemic:
Endocrinopathy: Diuretic use

Glucocorticoid SIADH Beer Potomania Urine Na
deficiency Psychogenic
polydipsia
< 20mEq: Edema-Heart

Treatment:
failure, cirrhosis, nephrotic > 20mEq: Renal failure
SIADH: Fluid restriction and
Urine > 20mEq: syndrome
diuretics, hypertonic fluid
Renal Losses Urine Sodium < 20mEq:
replacement.
Diuretics, osmotic Extrarenal losses:
Replace hormones.
diuresis, Emesis, Dehydration,
Correct fluid electrolyte
Mineralocorticoid Diarrhea, Burns
intake.
deficiency Treatment: Water and Na+
restriction, Diuretics.
Consider 25% albumin in
nephrotic syndrome.
Treatment: Fluid
replacement, remove
offending agents
Fig. 24.2 Hyponatremia workup
lality and hyponatremia. Type 2 renal tubu- –– Patients will be edematous, with possible
lar acidosis (RTA) (proximal) has salt and ascites, and hypertensive
bicarb wasting, along with other lab abnor- –– Low urine Na+ is expected
malities (see RTA in Chap. 23) • Euvolemic: Caused by fluid gain > sodium
• Hypervolemic hyponatremia: Decreased gain
effective intravascular volume and ADH –– Hypothyroidism, beer potomania, psycho-
release causes increased water retention genic polydipsia, ACTH deficiency
–– Can be seen in congestive heart failure, –– SIADH-retained water increases intravas-
renal failure, and nephrotic syndrome cular volume
Signs and symptoms calculated and generally replaced over

• True hyponatremia will be reflected in 24 h
hypo-osmolality • Correct < 0.5 mEq/h. Administer desmopres-
• Hypo-osmolality in ECF allows for a fluid sin if sodium increases too rapidly
shift into ICF, which leads to brain cellular • Hypovolemic: Replace intravascular volume
swelling and increased ICP/decreased cere- with NS, and remove offending agents
bral blood flow. These changes eventually • Hypervolemic: Water and Na+ restriction,
cause seizures, cerebral herniation, and apnea diuretics as needed. Consider 25% albumin in
• Symptoms: Nausea, vomiting, lethargy, altered nephrotic syndrome if severely
mental status, seizures, hypothermia, Cheyne– hypoalbuminemic
Stokes breathing, rhabdomyolysis. If hyponatre- • Euvolemic: Often corrects spontaneously
mia is chronic, patients may be able to maintain over 3–6 h with cessation of causative
low Na+ (< 110), as equilibration occurs activity
Treatment (Tables 24.4 and 24.5)

• If the patient is symptomatic, bolus with 3% W ater Intoxication
saline, correct serum sodium by 4–6 mEq/L
(1 mL/kg will raise by 1 mEq) Etiology
• If asymptomatic, rapid correction can result in • Occurs with excess water intake (dilutional
central pontine myelinolysis. This condition hyponatremia) and decreased ADH secretion
evolves over several days and features altered where water intake > kidney excretory
mental status, spastic quadraparesis, and, ability
eventually, death. This usually occurs in • Occurs in infants < 6-months-old with incor-
chronic hyponatremia rectly mixed formula, athletes replacing
• Calculate maintenance fluid sweat losses with water (e.g., marathon run-
• Calculate fluid loss 1 g =1 mL. Na deficit is
+ ners), forced water intake, iatrogenic IV flu-
8 mEq/100 mL of fluid lost ids, beer potomania (water > sodium
• Then calculate excess Na deficit = [140 −
+ content)
current serum Na (mEq/L)] × 0.6 × total body
+
weight (kg) Features

• Using the child’s baseline weight, mainte- • See Hyponatremia
nance and deficit fluid and electrolytes are
Table 24.4 Calculation of intravenous rehydration in cases of hyponatremia

Fluids Na+ K+
Maintenance fluids Maintenance fluid requirements 3 mEq/100 mL 2 mEq/100 mL
Deficit fluids 1 mL: 1 g of weight lost 8 mEq/100 mL lost 6 mEq/100 mL lost
Additional Na+ deficit – (140 − serum Na+) × 0.6 × wt –
(kg)
Bolus – – –
Total Maintenance + deficit − bolus – –
Table 24.5 An example of how to calculate and how to order intravenous fluid (IVF) in cases of hyponatremic
dehydration
A 20 kg child with Na+ 130 and 10% dehydration who received 20 cc/kg 0.9% normal saline bolus × 1
Maintenance Weight of 20 kg = 1500 mL 1500 mL/100 mL = 15 1500 mL/100 mL = 15
15 × 3 mEq = 45 mEq/24 h 15 × 2 mEq = 30 mEq/24 h
Deficit 20 kg × 0.1 = 2 kg = 2000 mL 2000 mL/100 = 20 2000 mL/100 = 20
20 × 8 = 160 mEq 20 × 6 = 120 mEq
Additional Na+ deficit [140–130] × 20 kg × 0.6 = 120 mEq 120 mEq –
Bolus −400 mL −61.6 –
Total 3100 mL 263 mEq (rounded) 150 mEq
Fluid rate: 3100/24 h = 129 mL/h
DEHYDRATION ehydration and Maintenance Fluid

D
Calculations
See Hypernatremia and Hyponatremia Maintenance Fluid Requirements
• Holliday–Segar method for maintenance fluid
and calorie calculation. 1 mL = 1 kcal:
Isonatremic Dehydration –– First, 10 kg—100 cal/kg/24 h
–– Next, 10–20 kg—50 cal/kg/24 h
• Na+ will be normal. Patients may have ele-
–– For every kg above 20 kg—20 cal/
vated BUN/Cr ratio and increased SG in urine
kg/24 h
> 1.025 in children, > 1.015 in infants
–– For every 100 calories metabolized in 24 h,
• Decreased bicarbonate if there is diarrhea and
an average healthy child will require 100–
vomiting. Anion gap is variable
120 mL of H2O, 2–4 mEq of Na+, and
• Vital sign changes include tachycardia and
2–3 mEq of K+
narrow pulse pressure
–– Consists of urine (60% of maintenance
Fluid replacement: Stepwise process fluid), stool (5%), and insensible losses
(25–40% depending on age, so ~33%)
1. Patient with hemodynamic instability character-
ized by severe dehydration, e.g., for increased Classification of Dehydration by Severity
capillary refill time and low blood pressure (Table 24.6)
(BP), will need initial fluid bolus with isotonic • Calculate fluid deficit (L) as pre-illness wt.
solutions such as NS (kg) – post-illness wt. (kg)
2. Maintenance fluids, 3 mEq/100 mL sodium,
• Dehydration % = [(pre-illness wt.−post-ill-
2 mEq/100 mL potassium ness wt.)/pre-illness wt.] × 100
3. Deficit fluids: Add Na+ 8 mEq/100 mL of fluid –– Mild dehydration = 5% in infants and 3%
lost, K+ 6 mEq/100 mL of fluid lost in children > 1 year
4. Subtract bolus fluids –– Moderate = 10% in infants and 6% in chil-
dren > 1 year
–– Severe = 15% in infants and 9% in children
> 1 year
Table 24.6 Assessment of dehydration based on clinical signs

Mild Moderate Severe
Skin turgor Normal Tenting None
Skin (touch) Normal Dry Clammy
Buccal mucosa/lips Dry Dry Parched/cracked
Eyes Normal Deep set Sunken
Tears Present Reduced None
Fontanel Flat Soft Sunken
Central nervous system Consolable Irritable Lethargic/obtunded
Pulse rate Normal Slightly increased Increased
Pulse quality Normal Weak Feeble/impalpable
Capillary refill Normal ~2 s > 3 s
Urine output Normal to decreased Decreased Anuric
Extremities Warm Cool Cold/mottled/cyanotic
Oral Rehydration for Mild and Moderate • Abnormal serum sodium values
Isonatremic Dehydration • Glucose malabsorption
• Mild-to-moderate isonatremic dehydration
can be treated effectively with oral rehydra- Calculating Replacement in Isonatremic
tion solutions Dehydration (Table 24.7)
• Replace 50–100 mL/kg body weight over • Deficit calculations and fluid therapy in
2–4 h isonatremic dehydration:
• Administer 5 mL with teaspoon, syringe, or –– With this type of dehydration, there is loss
dropper every 5 min as tolerated of both fluid (fluid deficit) and electrolyte
• Ondansetron administration to children (solute deficit) in a proportional manner
with severe vomiting can reduce the need – – Solute deficit: Total amount of electrolytes
for intravenous therapy and hospital lost
admission – – In illness < 3 days, 80% of the losses are
• Nasogastric tube can be used for replacement from ECF and 20% from ICF.
in cases of severe vomiting or painful oral –– In illness > 3 days, there is more intracel-
ulcers (herpangina) lular dehydration; hence, 60% of the losses
are from the ECF compartment and 40%
Fluids for oral replacement: from ICF compartment
• Oral rehydration solution –– Solute Na+ deficit (mEq) = fluid deficit (L)
• Pedialyte × proportion from ECF based on the dura-
tion of illness (0.8 or 0.6) × 140 mEq/L
Inappropriate fluids for replacements (extracellular sodium concentration)
• Water –– Solute K+ deficit = fluid deficit (L) × pro-
• Juices portion from ICF based on duration of ill-
• Sodas ness (0.2 or 0.4) × 160 mEq/L (intracellular
potassium concentration)
Contraindication of oral rehydration –– Replace maintenance and deficit evenly
• Circulatory instability or shock over 24 h.
• Altered mental status –– Remember to both supplement with main-
• Intractable vomiting tenance fluid and electrolyte requirement
• Bloody diarrhea or ileus and to replace ongoing losses
Table 24.7 An example of how to calculate and how to order intravenous fluid (IVF) in cases of isonatremic dehydration
A 20 kg child with Na+ 135 and 10% dehydration who received normal saline bolus × 1
Maintenance Weight of 20 kg = 1500 mL 1500 mL/100 mL = 15 1500 mL/100 mL = 15
15 × 3 mEq = 45 mEq/24 h 15 × 2 mEq = 30 mEq/24 h
Deficit 20 kg × 0.1 = 2 kg = 2000 mL 2000 mL/100 = 20 2000 mL/100 = 20
20 × 8 = 160 2 × 6 = 120
Bolus −400 mL −61.6 –
Total 3100 mL 144 mEq (rounded) 150 mEq
Fluid rate: 3100/24 h =129 mL/h
POTASSIUM (K) –– Cellular breakdown: Rhabdomyolysis,

tumor lysis, hemolysis
• K < 1% in plasma –– Medications: Succinylcholine, beta-blockers
• Intracellular and extracellular concentration –– Exercise, increased serum osmolality (e.g.,
can be altered by: DKA)
––
Medications (e.g., insulin, beta-agonists, • Decreased excretion (e.g. ACE-I, NSAIDs)
beta-blockers) • Renal failure, hypoaldosteronism (e.g., con-
–– Change in pH: Acidosis and alkalosis genital adrenal hyperplasia [CAH]),
–– Exercise pseudohypoaldosteronism
–– Change in serum osmolality
Clinical features
• Affects membrane depolarization:
Hyperkalemia –– Electrocardiogram (EKG): Peaked T waves
→ ST depression, increased PR interval,
Definition flattened P wave → widened QRS → ven-
• K > 5.5 mEq/L in infants through adulthood tricular fibrillation
• Allow up to 6.5 mEq/L in term newborns –– Paresthesia, fasciculations, weakness
• Identify medications, causes of cellular shifts,
Regulation tumor lysis (elevated PO4, hyperuricemia),
• > 40% is transiently moved intracellularly hemolysis (anemia, hemoglobinuria), rhabdo-
with increased potassium load. Most is renally myolysis (elevated creatine kinase), and renal
excreted insufficiency. Assess acid/base, BUN/Cr for
• Aldosterone is the primary hormone involved dehydration, and DKA. In infants, consider CAH
in potassium excretion
Treatment
Causes • Stop implicated medications
• Pseudohyperkalemia • EKG if > 6.5 mEq/L:
–– Hemolysis (heel-stick, tourniquet) –– Ca++ gluconate: Stabilize membrane
• Excessive intake (rare) –– Transcellular shift into ICF: Insulin + glu-
• Transcellular shifts cose (fastest), bicarbonate, beta-agonist
–– Acidosis (albuterol nebulizer)
–– Removal (slower onset): Loop diuretics, Clinical features

sodium polystyrene sulfonate (Kayexalate). • EKG: Flattened T wave → ST depression, U
Begin dialysis if severe, as in renal insuffi- wave → ventricular fibrillation, torsades de
ciency and tumor lysis. Hemodialysis is pointes
preferred over peritoneal dialysis • Muscle weakness, cramps, paralysis,
constipation
Hypokalemia Diagnosis
• Urinary K+, K/Cr ratio (< 1.5 likely gastroin-
Definition testinal or transcellular, > 1.5 likely renal)
• K < 3.0 mEq/L • The transtubular potassium gradient (TTKG) =
K urine/K plasma × (plasma osmol/urine osmol)
Etiology > 4 = urinary losses, < 4 =nonrenal losses
• Pseudohypokalemia (extremely elevated
white blood cell count) Treatment
• Transcellular shifts • If symptomatic: Oral K+ preferred, IV K+
–– Alkalosis, decreased insulin, beta-blockers 1 mEq/kg, max 40 mEq/L
–– Occurs during correction of DKA if K+ is –– Use potassium chloride. If acidotic, use
not added potassium acetate or citrate
• Extrarenal • Can use potassium-sparing diuretics if there
–– Vomiting results in hypochloremic hypo- is evidence of renal insufficiency. Replace
kalemic alkalosis. Hypokalemia is further magnesium if low, since hypomagnesemia
exacerbated by increased aldosterone due can cause hypokalemia
to volume losses
–– Diarrhea, laxatives
◦◦ Diarrhea—hyperchloremic hypokalemic CHLORIDE (CL)
▪▪ Acidosis in diarrhea, alkalosis in lax-
ative abuse Hypochloremia
• Renal
–– RTA, diuretics Definition
–– Bartter syndrome (+hypercalciuria), • Cl < 97 mEq/L
Gitelman syndrome (hypomagnesemia)
–– Diuretic: Alkalosis, hypokalemia, high Causes
urine chloride, normal BP • Loss of body fluids (along with Na+) from
• Thyrotoxic periodic paralysis, more common prolonged vomiting, diarrhea, sweating, or
in Asian population high fevers. Seen in CF as hyponatremic
• Liddle syndrome: Gain of function of sodium hypochloremic metabolic alkalosis
receptor in distal tubule; features of hyperal- • Medications: Bicarbonate, corticosteroids,
dosteronism with hypertension diuretics, and laxatives
ACID–BASE Table 24.8 Compensatory processes

Acute Chronic
Background Metabolic CO2 = 1.5 + HCO3 + 8 –
acidosis (±2)
• Normal pH 7.35–7.45, normal HCO3− 20–28,
Metabolic CO2 = CO2 increases by –
normal PCO2 35–45 alkalosis 7 for every 10 increase
• Tip: Determine if pH is appropriate for CO2 of HCO3−
level: Drop the 7, and compare numbers after Respiratory HCO3− = 24 + 24 + 4
decimal point, e.g., CO2 35 and pH 7.35 is acidosis (PCO2 − 40/10) (PCO2 − 40/10)
Respiratory HCO3− = 24 − 2 HCO3− = 24 − 5
appropriate
alkalosis (40 − PCO2/10) (40 − PCO2/10)
Regulation
• Acid–base balance regulated by buffers • Respiratory compensation occurs within
–– Bicarbonate the major buffers—CO2 + 12–24 h; renal compensation takes days
H2O ↔ H+ + HCO3− • Compensation cannot correct to normal pH
–– NH4+ is produced to allow for acid excre-
tion in urine Compensatory Processes (Table 24.8)
Hint: Remember: 1–2–4–5 in respiratory acido-
Henderson–Hasselbalch pH = 6.1 + log[HCO3 / sis/alkalosis
−
CO2], or H = 24 × PCO2/(HCO3−) • Respiratory acidosis:

−
• CO2 regulated by lungs, HCO3 regulated by –– Acute: HCO3− will increase by 1 for every
kidneys 10 increase in CO2
• Increased renin–angiotensin–aldosterone sys- –– Chronic: HCO3− will increase by 4 for
tem stimulates HCO3− reabsorption (e.g., con- every 10 increase in CO2
traction alkalosis) • Respiratory alkalosis:
• Increased parathyroid hormone (PTH), acet- –– Acute: HCO3− will decrease by 2 for every
azolamide, and proximal RTA decrease 10 decrease in CO2
−
HCO3 reabsorption –– Chronic: HCO3− will decrease by 5 for
• CNS receptors sense increase or decrease in every 10 decrease in CO2
−
HCO3 and will decrease or increase respira-
tory rate (increase/decrease CO2) to maintain Acidosis, alkalosis
physiologic pH, respectively • Approach acid–base disorders stepwise:
1. pH: Acidotic/alkalotic? May be normal if
mixed acidotic/alkalotic disorder, but CO2
Acid–base disorder can be simple or mixed:
and HCO3− will be abnormal!
Simple
• Metabolic acidosis/alkalosis with respiratory 2. CO2: Elevated or decreased?
compensation or respiratory acidosis/alkalo- 3. Bicarbonate: Elevated or decreased?
sis with metabolic compensation 4. Compensation: Appropriate or inappropri-
ate (i.e., mixed disorder) (longer duration
Mixed of episode if renal compensation occurs)
• Bronchopulmonary dysplasia (BPD):
Respiratory acidosis and metabolic alkalosis Metabolic Acidosis
(furosemide)
• Respiratory failure and sepsis: Metabolic aci- • pH < 7.2 results in decreased cardiac contrac-
dosis and respiratory acidosis tility, pulmonary vasoconstriction, decreased
adenosine triphosphate (ATP), altered mental Normal anion gap

status, and coma • Loss of base: aka hyperchloremic meta
• Associated lab abnormalities: bolic acidosis. Causes: Hyperalimentation,
–– BUN/Cr ratio will be increased in either Addison’s disease, RTA, Diarrhea,
prerenal azotemia or renal insufficiency Acetazolamide, Spironolactone, Saline
–– DKA: Glycosuria, ketonuria infusion
–– Addison disease: Hypoglycemia, • RTA versus diarrhea can be differentiated
hyperkalemia based on the urine anion gap
–– Diarrhea is the most common cause –– Urine anion gap = Na+ + K+ − Cl−. Normal
(HCO3− lost in stool) < 10 mEq/L
–– RTA: Distal (type I) hypokalemia, hyper- –– NH4+ (i.e., acid loss) is unmeasured cation.
calciuria, failure to thrive, cannot acidify NH4+ is excreted with chloride to maintain
urine (pH > 5.5.) electroneutrality
–– Proximal (type II), usually with Fanconi –– Gap is negative (i.e., increased NH4+ excre-
syndrome: Glycosuria, hypokalemia, phos- tion, and therefore increased Cl− excretion)
phaturia, aminoaciduria, uric aciduria (pH in RTA
< 5.5.) –– Gap is normal or zero in diarrhea
–– Hyperkalemic (type IV): Decreased con-
centration or response to aldosterone;
CAH Metabolic Alkalosis
• Addition or decreased excretion of base
Anion gap
• Na+ – (Cl– + HCO3−). Normal gap 8–12 Causes
–– Gap represents unmeasured anion. • Emesis is the most common cause. (Decreased
–– Increased, i.e., gain of acid: The H+ is HCl as well as increased resorption of base
buffered by HCO3−, but the anions are since intravascularly depleted)
increased (e.g., lactate) and chloride is • Identify cause by determining urinary chlo-
unchanged ride level
–– Normal, i.e., loss of base: Loss of HCO3− –– Decreased urinary chloride (chloride
balanced by increased Cl− to maintain responsive): Volume depletion. Causes:
electroneutrality ◦◦ Emesis (including bulimia)
◦◦ Diuretics (after effects wear off, chlo-
Increased anion gap ride returns to normal)
• Gain of acid: MUDPILES: Methanol, ◦◦ CF
Uremia, DKA, Phenformin (metformin) iron, ◦◦ Laxatives
INH, IEM, Lactic acidosis, Ethylene glycol/ –– Elevated urinary chloride level (chloride
ethanol, Salicylates resistant): Does not respond to fluid
• Methanol, ethylene glycol intoxication: replacement. Causes:
There is typically < 10 mOsm/kg difference ◦◦ If high BP (think elevated aldosterone
between calculated serum osmolality picture): Renin-secreting tumor, adrenal
(2Na + BUN/2.8 + glucose/18) and adenoma, Cushing, Liddle, 11B hydrox-
measured serum osmolality. If intoxication ylase (aka apparent mineralocorticoid
is present, there will be > 10 mOsm/kg dif- excess), 17-a-hydroxylase
ference between measured and calculated ◦◦ Normal BP: Gitelman, Bartter; hypo
osmolality parathyroidism. Rarely CF
Clinical Features –– Oral rehydration solutions have a serum

• Depends on underlying disease osmolality between 200 and 310, with
• Chloride responsive, i.e., volume depletion: approximate equimolar distribution of
Lethargy, thirst sodium and glucose. ORS hasten the
• Chloride unresponsive: Hypertension. absorption and improve the diarrhea
Cardiac arrhythmias, hypomagnesemia, –– If glucose/sodium ratio (e.g., fruit juices),
increased potassium losses, and increased or sodium/glucose ratio > 1:1 (broth);
shift into ICF. May have signs and symptoms excess is eliminated as diarrhea. They may
of hypokalemia. Ionized Ca++ decreases due worsen the diarrhea
to increased binding to albumin → tetany, • Replace diarrheal losses 1 mL/1 mL or
seizure replace 10 mL/kg body weight for each
diarrheal episode and 2 mL/kg body weight
Diagnosis for each episode of emesis
• Measure urinary chloride, renin, and aldoste- • If severe dehydration, shock, worsening
rone (differentiate adrenal tumor, renovascu- dehydration despite oral therapy, or ileus, use
lar disease, and adrenal etiology) IV fluid therapy and treat as in shock
• Switch to oral therapy when feasible
Treatment • Breastfeeding and milk-based formula can be
• Underlying etiology. Mild, will resolve. used; avoid high-glucose/low-sodium (e.g.,
Proton pump inhibitors in vomiting, sports drinks)
potassium-sparing diuretics. K+ supplements,
arginine will raise K+, acetazolamide.
Chloride responsive: NaCl and KCl. Liddle: O liguria/Acute Renal Failure
Amiloride or triamterene
Background
• Patients with oliguria/acute renal failure are
DISEASE STATES AND SPECIFIC at risk for fluid overload and electrolyte
THERAPY abnormalities
• Maintenance fluid (see Maintenance Fluid
Gastroenteritis Requirements) is equal to total body fluid
loss—urine (60% of maintenance fluid), stool
Background (5%), and insensible losses (25–40% depend-
• Formerly a major cause of mortality in under- ing on age, so ~33%)
developed countries • In severe oliguria, the goal is to avoid fluid
• Excessive fluid losses lead to hypovolemia, overload. Replace insensible losses (25–40%
metabolic acidosis, and shock of maintenance); administer diuretics as needed
and then replace urine mL/mL. Do not
Treatment supplement potassium until patient is able to
• Oral (can be used in mild and moderate void
dehydration)
• Goal is to maintain serum osmolality and
decrease diarrheal load Hyperosmolar Nonketotic Coma
• Oral rehydration solution versus juices or
broth: Background
–– Na reabsorption is impaired in diarrheal
+ • Typically occurs in Type 2 DM, since these
states, so cotransport with glucose is patients have enough insulin on board to con-
required to maintain Na balance
+
tinue glycolysis and prevent ketone synthesis. of the electrolytes shows evidence of
Therefore, no acidosis correction.
• Occurs after prolonged urinary losses, more • Weighing patients with dehydration twice a
dehydrated than DKA, and a high mortality day provides another reliable tool in deter-
mining the success of the fluid balance
Treatment correction.
• Aggressive fluid resuscitation with multiple • Severe dehydration may require a combina-
boluses of NS is the most important tion of both parenteral and enteral fluids via
component nasogastric tube, if the patient is not in shock
• Insulin therapy is not as important, as ketosis or on pressors.
and acidosis are not major features of this • A patient with profuse diarrhea will have
condition. Therefore, ensure adequate fluid metabolic acidosis from loss of alkaline pan-
resuscitation prior to insulin administration creatic fluids. A patient cannot be diagnosed
with renal tubular acidosis for 2 weeks fol-
lowing a diarrheal illness before the enteral
PEARLS AND PITFALLS acid–base balance restores.
• When possible, always choose enteral rehy-

dration over parenteral rehydration—it is
Suggested Reading
more physiologic and less prone to causing
major electrolyte abnormalities. Cross JT, Hannaman RA. MedStudy: pediat-
• When correcting the fluid and electrolyte rics board review core curriculum. Colorado
imbalance of a patient over a period of 48 h, Springs: MedStudy; 2018. Print.
the maintenance needs for that period of Kliegman RM, Stanton B, St Geme J, Schor N,
time have to be included in the Behrman RE. Nelson textbook of pediatrics.
calculations. 20th ed. Philadelphia: Saunders Elsevier; 2016.
• All fluid balance corrections have to be Powers K. Dehydration: isonatremic, hypona-
accompanied by regular monitoring of the tremic, and hypernatremic recognition and man-
progress by obtaining a basic metabolic panel agement. Pediatr Rev. 2015;36(7):274–85.
or venous blood gas every 4 h in the acute Rudolph CD. Rudolph’s pediatrics. 22nd ed.
phase (first 12 h) and every 6 h once the trend New York: McGraw-Hill, Medical Pub.
Division; 2003.
Urology
25
Catherine J. Chen and Micah A. Jacobs
URINARY TRACT INFECTION • The most common organism causing UTI in

children is Escherichia coli
(UTI) • Other bacterial pathogens include
Pseudomonas aeruginosa (non enteric Gram
Definitions negative), Enterococcus faecalis, Klebsiella
• Sterile pyuria: Presence of white cells in the pneumoniae, and group B Streptococcus (pre-
urine in the setting of a negative culture (≥ 3 dominantly in neonates)
WBC hpf or positive leukocyte esterase on • Most UTIs in sexually active females are
dipstick) caused by E. coli or Staphylococcus
• Asymptomatic bacteriuria: Urine culture with saprophyticus
significant bacterial colony count in an • Diagnosis of UTI depends on obtaining accu-
asymptomatic patient rate urine culture findings (Table 25.1)
• Uncomplicated UTI: Positive urine culture in • No laboratory tests can reliably distinguish
a symptomatic patient (frequency, urgency, cystitis from pyelonephritis
new urinary incontinence)
• Complicated UTI: Urine culture with signifi- Risk factors
cant bacterial colony count and associated • Constipation is a high-risk factor for recur-
urologic abnormalities (hydroureter, hydro- rent UTI
nephrosis, and vesicoureteral reflux) • Uncircumcised male infants
• Pyelonephritis: Positive urine culture plus
fever Table 25.1 General criteria to diagnose a urinary tract
infection
Background Method of
• Most UTIs are bacterial infections of the urine
mucosal surface of the urinary tract collection Interpretation
• The infection may occur anywhere from the Bag collection Not recommended. However, if done, and
urine analysis is suggestive of an infection,
urethra to the renal parenchyma a catheterized or suprapubic aspiration
• A temperature greater than 38 ° C may help must be completed. If culture is sent, there
to differentiate acute pyelonephritis from is high false-positive rate
lower tract UTI Urethral Pyuria on urine analysis and > 50,000
catheterization colony forming units/ml of a uropathogen
Midstream on culture
C. J. Chen · M. A. Jacobs (*) urine analysis
Department of Urology, University of Texas Southwestern Medical Suprapubic
Center, Dallas, TX, USA aspiration
e-mail: micah.jacobs@childrens.com

842 C. J. Chen and M. A. Jacobs
• Dysfunctional elimination syndrome (bowel dard for diagnosing acute pyelonephritis

bladder dysfunction, including urinary hold- and renal scarring
ing behaviors) –– For the purpose of diagnosing renal scar-
• Indwelling or intermittent catheterization ring, DMSA scintigraphy should be per-
• Anatomical abnormalities, including vesico- formed 3 months after acute infection to
ureteral reflux and bladder outlet obstruction allow resolution of acute reversible
lesions
Clinical presentation (by age group)
• Presence of fever and urine infection is highly Acute management (review American Academy
suggestive of pyelonephritis of Pediatrics [AAP] guidelines)
• Newborn (birth–1 month) • Uncomplicated UTI: Trimethoprim-
–– Fever sulfamethoxazole (TMP-SMX) twice a day
◦◦ May be the only presenting symptom or appropriate culture-specific antibiotics for
without a clear source of infection 3–7 days
◦◦ Temperature elevations greater than • Acute pyelonephritis: 7–10-day oral regimen
38.0 °C are indicative of upper UTI if > 3 months and if able to maintain hydra-
• 1 month–24 months tion as an outpatient. Recommend urology
–– Fever, hypothermia, vomiting, difficulty feed- referral
ing, cloudy or malodorous urine, frequency,
irritability, hematuria, or failure to thrive Management of recurrent UTI
• Preschool (2–6 years) • Referral to urology for further workup for
–– Abdominal pain, suprapubic pain, costo- anatomical abnormalities and discussion of
vertebral angle pain, dysuria, urgency, or prophylaxis antibiotics. Prophylaxis antibiot-
incontinence (day- or nighttime) in a previ- ics are not always indicated. While prophy-
ously toilet-trained child laxis antibiotics may decrease UTIs, there is
–– Pyelonephritis in young children is more increased risk of bacterial resistance in those
likely to manifest as vague abdominal dis- on prophylaxis antibiotics. There are no stud-
comfort rather than as the classic flank pain ies that demonstrate its efficacy in reducing
and tenderness observed in adults renal scarring
• Common prophylaxis regimens
Imaging –– TMP-SMX: 2 mg/kg as a single daily dose
• Ultrasonography or 5 mg/kg twice a week
–– Renal ultrasonography is the safest and –– Nitrofurantoin: 1–2 mg/kg as a single daily
fastest method for detecting congenital dose
renal and urinary tract anomalies such as
hydronephrosis
• Cystography Vesicoureteral Reflux (VUR)
–– Fluoroscopic voiding cystourethrography
is the gold standard for diagnosing vesico- Background
ureteral reflux • VUR or the retrograde flow of urine from the
–– Other methods include radionuclide cysto- bladder into the ureter
gram and contrast-enhanced ultrasound • Anatomic and functional disorder that can
• Renal scan result in substantial morbidity, both from
–– Dimercaptosuccinic acid (DMSA) scintig- acute infection and from the sequelae of
raphy currently is the accepted gold stan- reflux nephropathy
25 Urology 843
Fig. 25.1 Grades of

vesicoureteral reflux (VUR)
Grade I Grade II Grade III Grade IV Grade V
International Classification System for VUR the renal pelvis) should be evaluated postna-
(Fig. 25.1) tally, with an ultrasound after 48 h of life
• Grade I—Reflux into non-dilated ureter • Voiding cystourethrography (VCUG)
• Grade II—Reflux into renal pelvis and caly- –– VCUG is the gold standard in the diagnosis
ces without dilation of VUR, providing precise anatomic detail
• Grade III—Reflux into renal pelvis and caly- and allows grading of the reflux
ces with dilation • Radionuclide cystography
• Grade IV—Reflux with moderate ureteral –– Lower radiation doses than with VCUG
tortuosity and dilation of pelvis and –– This study provides less anatomical defini-
calyces tion but has higher sensitivity in detecting
• Grade V—Reflux with gross dilation and tor- reflux compared to VCUG
tuosity of ureter, pelvis, and calyces and loss
of papillary impressions Management
• General principles of management in chil-
dren with known VUR
Clinical presentation –– Spontaneous resolution of VUR is com-
• Children with VUR may present with hydro- mon in young children with low-grade
nephrosis and/or pyelonephritis (febrile reflux
UTI) –– Severe reflux is unlikely to resolve
• Hydronephrosis is often prenatally identified spontaneously
using ultrasonography –– Sterile reflux, in general, does not result in
• Infants can manifest as failure to thrive with reflux nephropathy
or without fever; other features include vom- –– Long-term antibiotic prophylaxis in chil-
iting, anorexia, and lethargy dren has been associated with increased
• Older children may report voiding symptoms antibiotic resistance
or abdominal pain –– Surgery to correct VUR is highly
successful
Diagnosis • Constipation is extremely common and may
• Diagnosis is based on imaging studies be a much more important etiologic factor
• Imaging with ultrasound after the first UTI is than the reflux itself
indicated in children of any age with febrile –– Constipation is a higher risk factor for
UTI infection than reflux; it is extremely impor-
• Children with prenatally identified hydrone- tant that the constipation is addressed
phrosis (> 7 mm anteroposterior diameter of
• Time voiding and double voiding may improve Society of Fetal Ultrasound (SFU) grading of
symptoms of dysfunctional voiding and hydronephrosis
reduce the risk of infection in select patients • Grade 1: Normal parenchyma with slight
• Serum chemistries are used to assess for base- splitting of the renal pelvis
line renal function • Grade 2: Normal parenchyma with full renal
• A complete blood count (CBC) report can pelvis and dilation of the major calyces
assist in tracking the response to treatment • Grade 3: Normal parenchyma dilation of the
• Urinalysis helps to determine the presence of minor calyces
proteinuria, which indicates possible renal • Grade 4: Loss of normal parenchyma
impairment
Antibiotic prophylaxis • Maternal ultrasound may reveal fetal
• If used, it is started once a child has com- hydronephrosis
pleted treatment of the initial UTI • Palpable renal mass in newborn infants
• There are conflicting studies regarding the • Abdominal flank pain
utility and efficacy of antibiotics in reflux. If • Febrile UTI
used, the duration is based on shared decision- • Hematuria after minimal trauma
making between the parents and physician • More common on the left side
• Discontinue if no VUR is seen on imaging
studies Diagnosis
• Antibiotics are usually administered as sus- • Renal ultrasound
pensions once daily, typically in the evening to • A VCUG is not always necessary in isolated
maximize overnight drug levels in the bladder UPJ obstruction but, to rule out urethral
• In infants younger than 3 months, the agent of obstruction, should be considered in boys
choice is amoxicillin with bilateral hydronephrosis
• For older children, the most common antibi- • A 99mTc-mercaptoacetyltriglycine (MAG3)
otics used are TMP-SMX and nitrofurantoin renal scan can be used once diagnosis is made
to determine renal function and drainage
Accepted indications for surgical treatment
• Breakthrough febrile UTIs despite adequate Management
antibiotic prophylaxis • Ultrasound 48 h after birth
• Severe reflux (grade V or bilateral grade IV) • Urology referral
that is unlikely to spontaneously resolve • Low-grade hydronephrosis may resolve, but
• Renal scarring on DMSA scan referral is appropriate
• Parental choice • If hydronephrosis is high grade (SFU grade 3
• Poor renal growth or function or appearance or 4), spontaneous resolution is less likely
of new scars • Surgical intervention and timing of intervention
for an obstructed UPJ are dependent on imaging
findings, history of UTIs, and shared decision-
Ureteropelvic Junction Obstruction making between the family and physician
Definition
• Ureteropelvic junction (UPJ) obstruction is U reterocele
defined as an obstruction of the flow of urine
from the renal pelvis to the proximal ureter Background
• UPJ obstruction is the most common obstruc- • Ureterocele is a cyst outpouching of the distal
tive lesion ureter into the urinary bladder, typically diag-
25 Urology 845
nosed after prenatal imaging demonstrating Clinical presentation

hydronephrosis • PUV should be considered if there is inability
• Ureteroceles may be asymptomatic and to empty bladder or weak urine stream
present with a wide range of clinical signs • If unrecognized during the neonatal period,
and symptoms, from recurrent cystitis to may present later with failure to thrive, ure-
bladder outlet obstruction or renal failure mia, sepsis, and renal failure
• If less severe, may present with UTI or uri-
Clinical presentation nary incontinence at later age
• Prenatal imaging
• UTI Diagnosis
• Urosepsis • Established with VCUG
• Obstructive voiding symptoms
• Urinary retention Treatment
• Failure to thrive • Transurethral ablation of the valve leaflets by
• Hematuria endoscopy
• Cyclic abdominal pain
• Ureteral calculus
Female Urethral Prolapse
Diagnosis
• The first-line imaging study for evaluating Background
the upper and lower urinary tract in children • Urethral prolapse is a circular protrusion of
is renal and bladder ultrasonography the distal urethra through the external meatus.
• VCUG is essential to evaluate the lower uri- It is a rarely diagnosed condition that occurs
nary tract for a ureterocele, posterior urethral most commonly in prepubertal black females
valve (PUV), ectopic ureter, and vesicoure- and postmenopausal white women
teral reflux • Risk factors for urethral prolapse in children
include increased intra-abdominal pressure as
Management a result of chronic coughing or constipation
• Observation alone is rarely a good option in
symptomatic ureteroceles Clinical presentation
• Antibiotic prophylaxis starts in newborns • Vaginal bleeding associated with urethral
with prenatal diagnosis of ureterocele mass is the most common presentation
• Indication for surgery depends on the site of
Management
the ureterocele, the clinical situation, associ-
• Treatment of urethral prolapse ranges from
ated renal anomalies, and the size of the
applications of estrogen creams to sitz baths
ureterocele
• Surgery may be indicated in severe, persis-
tent, or symptomatic cases
Posterior Urethral Valves (PUV)
Background rune-Belly Syndrome
P
• The most common cause of severe obstruc- (Eagle-Barrett Syndrome)
tive uropathy in male infants
• Posterior urethral dilation, bladder muscle • Deficient abdominal muscles
hypertrophy, hydronephrosis, renal dysplasia, • Undescended testes
and renal failure will depend on the severity • Urinary tract abnormalities
of obstruction • Massive dilation of ureters and upper tracts
• Very large bladder oligohydramnios and pul- ◦◦ Medication (i.e., anticholinergics such
monary hypoplasia as oxybutynin, mirabegron)
• Various degrees of renal dysplasia ◦◦ Surgical (Botox injection)
–– Stress incontinence. This is more com-
monly seen in the adult patient; however, it
Urinary Incontinence may be seen in very athletic children (espe-
cially girls)
Background ◦◦ Behavior modification (i.e., timed
• Most children will have control of micturition voiding)
by age 4–5 years ◦◦ Pelvic floor strengthening exercises
(Kegel exercises)
Causes
◦◦ Surgical intervention (i.e., injection of
• UTI
bulking agents, placement of artificial
• Constipation
sphincters or slings). Treatment is tailored
• Child abuse
to each patient and clinical situation
• Psychosocial stressor
• Back or sacral anomalies and underlying spi-
nal cord malformation Bladder Exstrophy
• Labial adhesions resulting in incontinence
from vaginal voiding • Bladder exstrophy is the externalization of
• Female epispadias the bladder plate on the anterior abdominal
• Ectopic ureter wall
• Bladder outlet obstruction • Bladder should be covered with plastic wrap
to keep bladder mucosa moist
• Application of gauze or petroleum gauze
• Ectopic ureter: Continuous urinary leakage
should be avoided because significant inflam-
• Detrusor instability: Signs of urinary urgency,
mation will result
such as bouncing up and down
• Consult pediatric urologist
• Stress incontinence: Occurs with Valsalva,
coughing, or sneezing
Diagnosis ypospadias
H
• Depends on history and physical
Background
examination
• The most common congenital anomaly of the
• Urinalysis and urine culture
penis
• Renal ultrasound
• The meatus can be in a ventral position from
• Magnetic resonance imaging (MRI) on the
the distal penis to the perineum
back if spinal cord or vertebral malformation
• Some mild forms may not need surgical
is suspected
correction
• Assessment of constipation
• Associated with chordee, which is more
Treatment severe in proximal hypospadias cases
• Depends on the etiology of incontinence
–– Ectopic ureter: Surgical Management
–– Detrusor instability • If there is a complete foreskin, circumcision
◦◦ Behavior modification (i.e., timed void- can be performed
ing, address constipation) • Consult a urologist for surgical decision-
making and counseling
25 Urology 847
Phimosis Treatment
• Topical steroids and topical or oral antibiotics
Background • Eventual circumcision may be indicated,
• Phimosis occurs when foreskin cannot be especially if recurrent
retracted
• Most boys will be able to retract their fore-
skins by age 5 years old; however, some may Circumcision
not be able to until their teen years [1]
AAP Circumcision Policy Statement [2].
• Physiologic phimosis: Seen in all newborn
• “Existing scientific evidence demonstrates
males in normal development of congenital
potential medical benefits of newborn male cir-
adhesions between the foreskin and glans
cumcision; however, these data are not sufficient
• Pathologic phimosis: Nonretractile foreskin
to recommend routine neonatal circumcision.”
secondary to scarring of the prepuce
• “In circumstances in which there are poten-
Treatment tial benefits and risks, yet the procedure is not
• In causes of pathologic phimosis, corticosteroid essential to the child’s current well-being,
cream to foreskin may be tried prior to surgery parents should determine what is in the best
• Indications for circumcision include UTI and interest of the child.”
known anatomical abnormalities such as • “To make an informed choice, parents of all
reflux, balanitis obliterans xerotica (BXO), male infants should be given accurate and
and balanoposthitis unbiased information and be provided the
opportunity to discuss this decision.”
• “If a decision for circumcision is made, pro-
Paraphimosis cedural analgesia should be provided.”
Description Indication of circumcision

• Paraphimosis is the inability to place the • Many families choose to have their male
retracted foreskin to its anatomical position infants circumcised for cultural, religious, or
• Foreskin retracted past the coronal sulcus may hygienic reasons. Only a few accepted medi-
become edematous, making the replacement cal indications are recognized: pathologic
of the foreskin over the glans more difficult phimosis, history of paraphimosis, or
balanoposthitis
Treatment
• Reduction is emergent and may require seda- Anatomic contraindication
tion and anesthesia • Hypospadias with incomplete foreskin
• Reduction can be done by compressing the • Epispadias
penis to decrease edema, application of sugar or • Ambiguous genitalia (including bilateral
D50 on the edematous foreskin, and pinpricks cryptorchidism or micropenis)
to the foreskin to allow egress of the edematous • In more severe cases of the following, cir-
fluid. The use of a penile block may be helpful cumcision may be left to the discretion of the
urologist: chordee, penile torsion, penile
webbing, and buried penis
Balanoposthitis
Medical contraindications to neonatal
Definition circumcision
• Inflammation and cellulitis of prepuce and/or • Any current illness or medical condition that
glans penis requires monitoring
• Age less than 12–24 h esticular Torsion

T
• Known bleeding diathesis (e.g., hemophilia
or thrombocytopenia) Background
• Disorders of the skin or connective tissue that • Testicular or spermatic cord torsion is an
would impair normal healing emergency
• It occurs in one in 4000 males < 25 years old
Instruments usually used for circumcision • Most commonly in boys age 12–18
• Gomco clamp • Most occurs in tunica vaginalis
• Plastibell device
• Mogen clamp Clinical presentation (Table 25.2)
• Acute onset of pain
Complications • Nausea and vomiting
• Bleeding • Scrotal edema and redness
• Infection • Loss of cremasteric reflex
• Meatal stenosis • High-lying horizontal testis
• Penile skin bridges
Diagnosis
Education of the parents • Color-flow Doppler ultrasound; decreased
• Instruct parents concerning the occurrence of blood flow on the affected side
physiologic childhood phimosis, which can
last into the school-age years Management
• Stress the danger of forcibly retracting the • Rapid consultation by the urologist in sus-
foreskin for hygienic purposes pected cases
• The adhesions found between the inner pre-
puce and the glans naturally lyse Table 25.2 Differentiation between acute epididymitis and
• The AAP does not recommend routine neo- testicular torsion
natal circumcision; however, if circumcision Testicular torsion Epididymitis
is performed, the AAP recommends the use Inadequate fixation of E. coli in young children,
of procedural analgesia [2] testis within the scrotum gonococcus, or Chlamydia
after puberty is the most
common cause
Sudden onset (hours) Gradual onset (days)
Micropenis Usually nausea and Usually no nausea and
vomiting vomiting
Definition No dysuria, no frequency, May have fever, dysuria,
• Stretched penile length from pubis to the tip no fever frequency, and urethral
of the penis < 2.5 cm discharge
No pyuria Urinalysis usually reveals
Causes pyuria
Absent cremasteric reflex Normal cremasteric reflex
• Deficiency of gonadotropin secretion during Scrotum is swollen and Tenderness and induration
the last two trimesters testis is exquisitely tender occurring first in the
• Testosterone insensitivity and often difficult to epididymal tail and then
• Kallmann syndrome examine spreading
High-lying horizontal Normal position testis
• Prader-Willi syndrome
testis
• Panhypopituitarism Absent or decreased blood Increased blood flow occurs
flow in the affected with epididymitis on US
Treatment testicle on US
• Testosterone may be beneficial in selected Immediate surgical Antibiotics, NSAIDS, scrotal
cases exploration support/elevation
25 Urology 849
• Obtain immediate scrotal ultrasound through • Often masquerades as testicular torsion or

the emergency department or urgent care. Do epididymitis
not delay imaging
• Immediate exploration, detorsion, and con- Clinical presentation
tralateral testicular fixation are required • Acute scrotal pain
• Manual detorsion may be attempted after • Pain can be mild to severe
obtaining a testicular ultrasound • Often there is a palpable tender nodule at the
• In the majority of cases, torted testis rotates superior or inferior pole of the testicle with
inward (e.g., the left testis is rotated clockwise) blue discoloration (blue dot sign)
• Vertical orientation of the testes is preserved
Prognosis • The cremasteric reflex is usually intact
• Testes can be lost if the surgery was delayed • There is normal blood flow to the testicle
as little as 4 h, and by 24 h, infarction is • A reactive hydrocele may be seen
almost universal
Diagnosis
• Doppler ultrasound can differentiate between
Neonatal Testicular Torsion torsion of appendix and testis
• Testicular appendage torsion appears as a
Background
lesion of low echogenicity with a central
• Majority of the case is extravaginal torsion,
hypoechogenic area
which is the torsion of entire spermatic cord
and testis Treatment
• This can be a prenatal event (occurs in utero) • Usually resolves spontaneously
or a postnatal event (within the first 30 days • NSAIDs
of life)
ryptorchidism
C
• If the torsion occurred as a prenatal event,
the testicle is likely nontender; however, it Background
can be tender, depending on proximity of • Most common genital problem of newborn
the event to delivery. Scrotum can be males
discolored • Occurs in one-third of premature boys and in
• If the torsion occurred as a postnatal event, there 3–4% of newborn males
is usually acute tenderness, swelling, and over-
lying scrotal skin changes compared to previ- Clinical presentation
ously known normal scrotal physical exam • Diagnosis is made by physical exam
• Imaging is not indicated and should not be
Management performed before evaluation by a pediatric
• Testicular salvage is rarely successful urologist
• Contralateral testis should be fixed as precau- • Undescended testis can be intra-abdominal,
tionary measure in the inguinal canal, ectopic in the perineum,
or in the upper scrotum
• If the testis was down at birth, the diagnosis is
Testicular Appendage Torsion more likely retractile testis
• Retractile testis can be pulled down to the
Background
bottom of the scrotum
• Torsion of testicular appendix, which is a
• Most retractile testes eventually will end up
remnant of mesonephric tubule
in the scrotum
Treatment Management
• If the testicle has not descended by 6 months • Urgent same-day referral to a pediatric
of age, refer to a urologist for evaluation urologist or to the emergency department.
• The ideal timing for surgical intervention is Once the diagnosis of a testicular tumor is
between 6 and 18 months of age made, surgical management should not be
delayed
Prognosis • Surgical: Radical orchiectomy
• Undescended testes have increased risk of
cancer even after surgical correction
• Subfertility: Bilateral undescended testes have Varicoceles
been associated with infertility in about half of
cases Definition
• Abnormal dilation and tortuosity of the tes-
ticular vein and pampiniform plexus of sper-
matic cord
Testicular Cancer • Occurs most often on the left side. If present
on the right, consider obtaining an abdominal
Background
ultrasound to evaluate for any renal or retro-
• Accounts for approximately 1–2% of all
peritoneal masses
pediatric solid tumors
–– Typically occurs between ages 2 and 4 and Clinical presentation
then at puberty • Most patients are asymptomatic
• Compared to postpubertal testicular tumors, • Larger varicocele may feel and appear like a
prepubertal testicular tumors are more com- bag of worms
monly benign and, if malignant, then to have • Testicular size must be checked for any
better prognosis asymmetry
–– Teratoma is the most common benign tes- • Can contribute to infertility in some cases
ticular tumor in prepubertal boy • Can cause scrotal pain
• Germ cell tumors are the most common pedi-
atric testicular tumor Management
–– Yolk sac tumor is the most common tes- • Obtain renal ultrasound
ticular tumor in prepubertal boys • Surgery may be indicated if there is reduced
testicular growth, infertility, or pain
• Painless testicular mass (most common pre-
sentation). Occasionally detected in the setting Hydroceles
of some other scrotal pathology such as hydro-
cele, epididymitis, and testicular torsion Background
• Hydrocele is due to failure of fusion and
Diagnosis obliteration of the processus vaginalis
• Testicular ultrasound • Noncommunicating hydroceles usually
• Tumor markers (AFP, LDH, β-HCG) resolve by 1 year of age
• Staging imaging: CT abdomen/pelvis
• Pubertal patients should be encouraged to Management
perform regular self-exam • Observation
25 Urology 851
• The following factors indicate hydrocele Causes

repair: Failure to resolve by age 2 years, con- • The most frequently reported abnormalities
tinued discomfort, parental preference in children are hypercalciuria and
hypocitraturia
• Struvite stones
Inguinal Hernia –– Can grow quickly and form a large stag-
horn calculus with the bacteria becoming
Background trapped in the stone
• Develop in 1–5% of children –– Proteus is the most common urease-form-
• 5 to 10 × more common in boys and is more ing bacterial species
common in premature infants –– Recurrent UTIs are the greatest risk for
developing struvite stones
Presentation
• Painless mass in the groin, which can contain Clinical presentation
abdominal contents that may wax and wane • Pain, usually colicky
in size • Dysuria and frequency
–– This bulge may be present only in situa- • Passage of blood, stones, or gravel
tions of increased abdominal pressure, • Look for signs of renal or other metabolic
such as in Valsalva maneuvers, crying, or diseases such as renal tubular acidosis, Dent
straining disease, or Lesch-Nyhan syndrome
• Family history
Management
• Dietary history
• Inguinal hernias do not spontaneously heal
and must be surgically repaired Diagnosis
• All pediatric inguinal hernias require opera- • Urinalysis and urine culture
tive treatment to prevent the development of • Urine pH (< 6 for uric acid stones)
complications such as inguinal hernia incar- • Complete metabolic panel
ceration or strangulation • Uric acid
• Generally, a surgical consultation should be • Urine calcium (Ca) and creatinine
made at the time of diagnosis and repair • 24-hour metabolic urine evaluation
Imaging
Kidney Stones • Renal ultrasonography
• CT scan without contrast. Consider low-dose
Background CT scan
• Urolithiasis is an uncommon disease in chil-
dren, but recent studies have demonstrated an Management
increasing incidence in the pediatric • The greatest risk factors for calcium kidney
population stone formation are low fluid and high sodium
• Types of kidney stones intake
–– Calcium oxalate 40–65% • Decrease the risk of Ca oxalate by limiting
–– Calcium phosphate 14–30% intake to a modest amount of high-oxalate
–– Struvite 10–20% foods such as nuts and chocolates
–– Cystine 5–10% • Recommended dietary allowance (RDA)
–– Uric acid 1–4% should be encouraged
• No added salt diet der with a suprapubic catheter followed by

• Moderate amount of animal protein delayed evaluation and reconstruction
consumption • Surgical repair depends on the severity of
• Avoidance of excess vitamin C injuries
• Thiazide diuretic if hypercalciuria and does
not respond to a restricted sodium diet
• Antibiotic for infection-related (struvite) PEARLS AND PITFALLS
• Flomax (medical expulsive therapy) to help
with stone passage
• Refer children with recurrent febrile UTIs to
Surgical treatment a pediatric urologist for further anatomical
• Most stones smaller than 5 mm pass sponta- workup and management. The decision
neously in children and do not require surgi- regarding prophylactic antibiotics and their
cal intervention management is complex and should be shared
• Stones that are larger than 5 mm may require by family and physician.
nephrolithotomy or lithotripsy or endoscopies • The diagnosis of a UTI is based on a child
having both symptoms and a positive urine
culture.
Urethral Injuries • Refer children to a urologist if a testicle has
not descended by 6 months of age.
Background • Testicular torsion accounts for 20–30% of
• Trauma to the male urethra must be efficiently acute scrotum cases and is a surgical emer-
diagnosed and effectively treated to prevent gency. All families with boys should be coun-
serious long-term sequelae seled and educated about testicular torsion, as
• The etiology of a urethral injury can be clas- it is common for boys to delay notifying an
sified as blunt or penetrating adult of symptoms due to embarrassment.
• Iatrogenic injuries to the urethra occur when • Pubertal patients should be encouraged to
difficult urethral catheterization leads to perform regular self-exam.
mucosal injury with subsequent scarring and
stricture formation
• Diagnosis of urethral injuries requires a rea-
sonably high index of suspicion References
Clinical presentation 1. Care of the uncircumcised penis. Elk Grove

• Hematuria or inability to void Village: American Academy of Pediatrics,
• Decreased stream 1999. http://www.cirp.org/library/normal/aap-
• Blood at the meatus may be seen care1999/. Accessed 3 Nov 2018.
2. Circumcision policy statement. American
Academy of Pediatrics. Task force on circumci-
Diagnosis
sion. Pediatrics. 1999;103(3):686–93.
• The diagnosis of urethral trauma is made by
retrograde urethrography
Management Suggested Reading

• Consult pediatric urologist
• Bladder drainage must be established. Bani Hani O, Prelog K, Smith GH. A method to
Depending on the injury, the urologist may assess posterior urethral valve ablation. J Urol.
place a catheter or consider draining the blad- 2006;176(1):303–5.
25 Urology 853
Bomalaski MD, Anema JG, Coplen DE, Koo HP, Lannon CM, Bailey AGB, Fleischman
Rozanski T, Bloom DA. Delayed presentation AR. Circumcision policy statement. American
of posterior urethral valves: a not so benign con- Academy of Pediatrics. Task force on circumci-
dition. J Urol. 1999;162(6):2130–2. sion. Pediatrics. 1999;103:686–93.
Bushinsky DA, Coe FS, Moe OW. Nephrolithiasis. Practice parameter: the diagnosis, treatment, and
In: Brenner BM, editor. Brenner & Rector’s the evaluation of the initial urinary tract infection in
kidney, vol. 2. 9th ed. Philadelphia: Elsevier febrile infants and young children. Academy of
Saunders; 2012. p. 1455–507. Pediatrics. Committee on quality improvement.
Care of the uncircumcised penis. Elk Grove Subcommittee on UTI. Pediatrics. 1999;103(4
Village: American Academy of Pediatrics. Pt 1):843–52. Erratum in Pediatrics. 1999;103(5
1999. http://www.cirp.org/library/normal/aap- Pt 1):1052; 1999;104(1 Pt 1):118; 2000;105(1
care1999/. Accessed 3 Nov 2018. Pt 1):141.
Hutson J. Undescended testis, torsion, and vari- Weiss R, Duckett J, Spitzer A. Results of a ran-
cocele. In: Grosfeld JL, O’Neill JA, Coran domized clinical trial of medical versus surgi-
AG, Fonkalsrud EW, editors. Pediatric surgery. cal management of infants and children with
Philadelphia: Mosby Elsevier; 2006. p. 1193–214. grades III and IV primary vesicoureteral reflux
Johnson CE, Corey HE, Elder JS. Urinary tract (United States). The International Reflux Study
infections in childhood. Consens Pediatr. in Children. J Urol. 1992;148(5):1667–73.
2003;1:1–28.
Dermatology
26
SKIN DISORDERS ransient Neonatal Pustular

T
OF THE NEWBORN Melanosis No redness,present at
birth,leave behind
Erythema Toxicum Background dark pigmentations
• Cause unknown
Background • Classically occurs in dark-skinned newborns
• Cause unknown • Benign, self-limited condition in term infants
• Occurs in 50% of infants • Present at birth
• Benign, self-limited condition in term infants
• Usually begins 24–48 h after birth Clinical Presentation
• Fragile vesiculopustules and hyperpigmented
Clinical Presentation macules with a collarette of scale
• Discrete erythematous blotchy macules with • Hyperpigmented macules may persist for
central papule or pustule (Fig. 26.1) several months
• Affects the face, trunk, and extremities • Wright or Giemsa stain shows neutrophils
• Spares the palms and soles
• Wright or Giemsa stain shows eosinophils Management
• Lasts 1 week or less • Reassurance
Management
• Reassurance Miliaria
Background
• Obstruction of the eccrine ducts
• Miliaria crystallina: superficial ductal
obstruction, fragile vesicles resembling water
droplets on the skin (Fig. 26.2)
M. Craddock (*) • Miliaria rubra: non-follicular erythematous
Department of Dermatology and Pediatrics, Texas Children’s
Hospital, Baylor College of Medicine, Houston, TX, USA papules or pustules on the forehead, upper
e-mail: mfcraddo@texaschildrens.org trunk, flexural areas, or covered skin
J. Ruth (*)
Department of Dermatology and Pediatrics, Dell Children’s
Medical Group, Austin, TX, USA
e-mail: jennifer.ruth@ascension.org

856 M. Craddock and J. Ruth
a b
Fig. 26.1 (a) 5-day-old infant with erythema toxicum of the neck, chest, and abdomen (b) Scattered papules and pustules
with surrounding erythema on the abdomen and suprapubic skin
• Cool baths, air-conditioned environment, and

lightweight cotton clothing
Nevus Sebaceus (of Jadassohn)

Background
• Hamartoma of sebaceous glands, hair folli-
cles, and apocrine glands
• Rarely associated with neurologic, ocular, or
skeletal abnormalities
• Usually present at birth as a solitary, yellow-
Fig. 26.2 Miliaria crystallina: Scattered fragile vesicles on orange, round-to-oval, hairless plaque
the posterior neck of a child
• May become more verrucous during
adolescence
• Miliaria profunda: deepest level of obstruc- • Most common on the scalp (Fig. 26.3)
tion, white papules, can prevent adequate
sweating Management
• Clinical observation vs. surgical excision
Management • Prophylactic excision is controversial but can
• Avoid excessive heat, overdressing, or appli- be considered due to risk of thickening at
cation of thick emollients in hot, humid puberty and small risk of developing benign
climates > malignant neoplasms within the nevus
26 Dermatology 857
Table 26.1 Diaper dermatitis

Irritant Seborrheic
Diaper rash dermatitis Candidiasis dermatitis
Cause Moisture, Candida Unknown, may
friction, species represent an
enzymes in inflammatory
stool response to
Malassezia
furfur
Clinical Red patches Red patches Salmon-pink
presentation that involve involving patches with
convex convex areas greasy scale
areas; and inguinal involving convex
inguinal creases, areas and
creases are satellite inguinal creases;
spared papules and involvement of
pustules the scalp, face,
and
retroauricular
skin may be
present
Management Frequent Topical Topical
diaper antifungal antifungal cream
changes, cream or low-potency
highly topical
absorbent corticosteroid
diapers,
topical
Fig. 26.3 Nevus sebaceous: Yellow-orange verrucous
barrier
plaque on the scalp of an adolescent
creams or
ointments
with every
Diaper Dermatitis (Table 26.1 diaper
and Fig. 26.4) change
ECZEMATOUS DERMATITIS
Atopic Dermatitis
Background
• Chronic, inflammatory pruritic skin disorder
• Pathogenesis is multifactorial: genetic predis-
position, immune dysregulation, epidermal
barrier dysfunction, and environmental
triggers
• Increased risk of developing other compo-
nents of the atopic triad (asthma or allergic
Fig. 26.4 Young male with a diaper dermatitis secondary to
rhinitis)
candida. Note the erythematous satellite papules and pustules
Fig. 26.5 14-year-old male with eczema affecting the ante-

cubital fossa (Image courtesy of Sitratullah Olawunmi
Kukoyi-Maiyegun, MD, Department of Pediatrics, Paul
L. Foster School of Medicine, Texas Tech University Health
Sciences Center, El Paso, Texas)
• Symmetric, scaly, red patches and plaques,
often with overlying crust
• Distribution of rash is dependent upon the
age of the child
• Infants and toddlers: involvement of the face,
trunk, and extensor extremities
• Childhood: flexural areas such as the antecu- Fig. 26.6 Eczema herpeticum affecting the lower extremi-
bital and popliteal fossae (Fig. 26.5) ties of a toddler with known eczema. Note the scattered ery-
• Adolescents: flexural distribution but often thematous papules and punched-out erosions
develop lesions on the face, neck, and hands
soles with sparing of the interdigital spaces;
Complications cracking, fissures, or a “glazed appearance”
• Increased risk of skin infections including can be seen
Staphylococcus aureus, molluscum contagio-
sum, and herpes simplex virus Management
• Herpes simplex virus (“eczema herpeticum”): • Use of thick emollients such as ointments or
sudden onset of grouped vesicles and creams is the cornerstone of therapy
punched-out erosions, particularly within • Apply topical corticosteroids twice daily to
areas of atopic dermatitis (Fig. 26.6) areas of inflammation until resolved
• Topical corticosteroids vary in strength from
class VII (very low potency) to class I (very
Variants high potency). Therapeutic choice varies
• Nummular eczema: coin-shaped, pruritic, based upon severity and anatomic site, for
scaly, or crusted papules or plaques example:
• Dyshidrosis: recurrent or chronic vesicles –– Low-potency corticosteroids such as
that affect the palms, lateral fingers, and soles hydrocortisone 2.5% ointment are pre-
• Juvenile plantar dermatosis: erythematous ferred for delicate areas like the face, inter-
scaly plaques involving the distal toes and triginous skin, and genitals
26 Dermatology 859
–– Medium-potency corticosteroids such as C ontact Dermatitis

triamcinolone 0.1% ointment are appropri-
ate for the trunk or extremities Background
• Avoid the use of systemic corticosteroids • May be irritant or allergic (delayed hypersen-
• Alternative therapies to low-potency topi- sitivity reaction)
cal corticosteroids include topical calci-
neurin inhibitors (tacrolimus or Perioral Irritant Contact Dermatitis
pimecrolimus) or a topical PDE4 inhibitor • Form of irritant contact dermatitis from lick-
(crisaborole) ing lips
• Topical or systemic antibiotics as needed for • Also known as lip-licker’s dermatitis
secondary bacterial infections; bleach baths (Fig. 26.8)
can be used to decrease bacterial
colonization
Rhus Dermatitis (Poison Ivy)
Keratosis Pilaris • Form of allergic contact dermatitis caused by

urushiol from plant sap
• Folliculocentric papules with a central core of • Causes itching, erythema, papules, vesicles,
keratin debris, may have associated or bullae in a linear or irregular distribution
erythema • Fluid from ruptured vesicular or bullous
• Usually located on the cheeks, extensor sur- lesions does not spread eruption
face of the arms, and thighs (Fig. 26.7) • Management: immediate washing with soap
• Treatment is difficult; options include low- and water, cool compresses, topical cortico-
potency topical corticosteroids for associ- steroids, or antihistamines for pruritus; oral
ated erythema, topical retinoids, or corticosteroids, if used, should be tapered
emollients which contain an exfoliant (e.g. slowly over several weeks
lactic acid)
Fig. 26.7 Adolescent female with folliculocentric papules Fig. 26.8 Young male child with lip-licker’s dermatitis
on the extensor surface of the right arm consistent with kera-
tosis pilaris
Fig. 26.9 10-year-old male with a nickel contact dermatitis
Nickel Dermatitis
• Form of allergic contact dermatitis that devel-
ops from exposure to jewelry or metal clo-
sures on clothing (Fig. 26.9)
Seborrheic Dermatitis
Background
• Cause unknown, may be an inflammatory
response to Malassezia furfur Fig. 26.10 2-month-old baby with seborrheic dermatitis of
the scalp
• Salmon to pink patches with greasy scale
• Zinc deficiency results in a triad of the
involving the scalp, face, retroauricular
following:
creases, and diaper area
–– Well-demarcated eczematous to eroded
• Seborrheic dermatitis of the scalp (cradle
plaques surrounding the mouth, diaper
cap) is common in infants, which peaks at
area, and distal extremities
3 months of life (Fig. 26.10)
–– Alopecia
Management –– Diarrhea
• Mineral oil, ketoconazole or selenium sulfide
Management
shampoo, topical corticosteroids, or topical
• Zinc supplementation will lead to rapid
antifungals
improvement
Acrodermatitis Enteropathica
ACNE
Background
• An autosomal recessive disorder affecting the Acne Vulgaris
uptake of zinc
Background
Clinical Presentation • Obstruction of the pilosebaceous apparatus is
• Usually presents after being weaned from due to hyperkeratinization and increased
breast milk sebum production
26 Dermatology 861
• Inflammation is fueled by an increased den- • Antibiotics should be used in combination

sity of Propionibacterium acnes, a normal with benzoyl peroxide to decrease P. acnes
resident flora resistance
• Exacerbating factors: hormonal dysregula-
tion/increased androgen states; anabolic ste-
roids, corticosteroids, certain contraceptives, N
eonatal and Infantile Acne
and topical products/mechanical factors that
obstruct the pilosebaceous unit Background
• Types of acne: comedonal (open or closed • Neonatal acne starts in the first few weeks of
comedones), inflammatory (papules, pus- life
tules, nodules, cysts), mixed (comedonal and • Infantile acne starts at 3–6 months of age
inflammatory)
Clinical Presentation • Face is the primary site of involvement
• Open comedones (blackheads) • Neonatal acne: small inflammatory papules
• Closed comedones (whiteheads): white pap- and pustules most common (Fig. 26.12)
ules without surrounding erythema • Infantile acne: open and closed comedones
• Inflammatory acne: erythematous papules, most common
pustules, cysts, and/or nodules (Fig. 26.11) • Inflammatory lesions and scarring may occur,
• Can be associated with post-inflammatory especially with the infantile form
dyspigmentation or scarring
Management
Differential Diagnosis • Reassurance for neonatal acne (brief, self-
• Adenoma sebaceum (facial angiofibromas) limited eruption)
may be mistaken for acne vulgaris • Infantile acne: topical retinoids for comedo-
nal lesions
Management • Topical benzoyl peroxide or topical antibiot-
• Topical therapies such as retinoids and ben- ics for inflammatory lesions
zoyl peroxide
• Antibiotics (topical or systemic), hormonal
therapies, and oral retinoids may be consid-
ered for more severe disease
Fig. 26.11 Teenage male with papules, pustules, and rare Fig. 26.12 Neonatal acne: Scattered erythematous papules
nodules consistent with inflammatory acne vulgaris and pustules on the forehead and cheeks
Periorificial Dermatitis • African American children are disproportion-

ately affected as compared to other ethnic
Background groups
• Common acneiform facial eruption in • Presence of alopecia, scaling, and occipital
children lymphadenopathy is highly suggestive
• Use of topical or inhaled corticosteroids often
contributes to development Clinical Presentation
• Alopecia: one or more round oval patches of
Clinical Presentation partial to complete alopecia with associated
• Red papules and papulopustules occur around scaling (Fig. 26.14); T. tonsurans causes hair
the mouth, nose, and eyes (Fig. 26.13) breakage leaving behind black dots
• Seborrheic: mimics seborrheic dermatitis
Management with patchy or diffuse white to grayscale; alo-
• Topical antibiotics, such as metronidazole or pecia may be subtle
clindamycin • Inflammatory or kerion: severely painful
• For severe cases, oral tetracyclines or inflammatory reaction with deep, suppurative
erythromycin boggy lesions on the scalp (Fig. 26.15)
• Stop the use of topical corticosteroids and • Occipital lymphadenopathy is common
wash face after use of inhaled corticosteroids • A widespread papular dermatophytid rash, or
• Improvement is slow, often takes 6–8 weeks id reaction, can occur after starting systemic
to clear treatment
Diagnosis
FUNGAL INFECTIONS • Diagnosis is usually made clinically
• Fungal culture can be performed to confirm
Tinea Capitis infection
• Trichophyton tonsurans is the most common • Oral antifungal therapy is necessary for clear-
cause in the USA ance due to involvement of the hair follicle
• Most common in prepubertal children and
uncommon in infants and adults
Fig. 26.13 Child with periorificial dermatitis. Note the ery- Fig. 26.14 6-year-old male with tinea capitis of the scalp.
thematous papulopustules surrounding the mouth Skin findings include scalp scaling with associated alopecia
26 Dermatology 863
• Griseofulvin is the drug of choice (Table 26.2) T

inea Corporis
• Clearance requires at least 6 weeks or more
of therapy Background
• Adjunctive topical therapy with selenium sul- • Superficial fungal infection of the skin
fide or ketoconazole shampoo twice weekly caused by a dermatophyte (Trichophyton,
helps to reduce scales and curtail the spread Microsporum, and Epidermophyton)
of infection • Trichophyton rubrum is the most common
• Incision and drainage of a kerion is not infectious agent in the world
recommended
• Oral prednisone may be used for 2–4 weeks Clinical Presentation
for severe inflammatory tinea capitis • Single or multiple annular (ring-like) lesions
with a raised, erythematous, and scaly border
with central clearing
• Lesions are variably pruritic
Management
• Topical antifungal agents are effective
• Topical treatment should be applied twice
daily for at least 2–3 weeks
• Systemic therapy may be used for extensive
tinea corporis, immunocompromised
patients, or those cases refractory to topical
therapy
Fig. 26.15 Kerion secondary to tinea capitis. Note the ery-

thematous indurated alopecia plaque on the occipital scalp
Table 26.2 Common systemic antifungals

Drug name Mechanism of action Monitoring/warnings Tips
Griseofulvin Blocks mitotic spindle No routine monitoring needed in Commonly used for tinea capitis
healthy patients Limited efficacy for
onychomycosis
Not effective for tinea versicolor
Terbinafine Blocks cell wall synthesis (inhibits Advisable to check liver Not effective for tinea versicolor
squalene epoxidase) function before and during Commonly used for
therapy onychomycosis
Effective for tinea capitis,
especially Trichophyton species
Fluconazole Blocks cell wall synthesis (inhibits Can prolong the QT interval Effective for extensive/recurrent
lanosterol-14-alpha-demethylase) tinea versicolor
Itraconazole Blocks cell wall synthesis (inhibits Can prolong the QT interval Effective for extensive/recurrent
lanosterol-14-α-demethylase) tinea versicolor
Do not use in patients with Can use pulse dosing
ventricular dysfunction for onychomycosis
Advisable to check liver
function before and during
therapy
Tinea Cruris Management

• Topical antifungals to be applied until the
Background eruption clears
• Dermatophyte infection of the groin or upper • Severe or persistent cases may require oral
thighs antifungal therapy
• Caused by Trichophyton rubrum, Tricho • Keep feet dry and wear well-ventilated shoes
phyton mentagrophytes, or Epidermophyton or sandals
floccosum • Recommend regular use of absorbent pow-
• A warm, humid environment and tight-fitting ders in recurrent cases
clothing are predisposing factors
• More common in men and rare before puberty
Tinea Versicolor
• Erythematous patches and pustules on the Background
inner thigh and inguinal creases • Caused by yeast forms of Malassezia furfur
• Border of lesions is elevated with scale that invade the stratum corneum
• The scrotum and labia majora are commonly • Occurs in adolescents and adults, rare in
spared children
• May be intensely pruritic; scratching leads to
erosions, inflammation, and lichenification Clinical Presentation
• Small hypopigmented or hyperpigmented
Management round or oval macules located on the trunk,
• Topical antifungal until clearance, usually proximal extremities, and/or neck
3–4 weeks (Fig. 26.16)
• Avoid tight-fitting clothing and dry after • Individual lesions may coalesce into large
bathing patches
• May use absorbent powder such as Tinactin • Sun exposure may accentuate the appearance
in fair-skinned individuals
Tinea Pedis
Background
• Dermatophyte infection of the feet
• Caused by Trichophyton, Epidermophyton, or
Microsporum
• Common in adolescents and adults
• Interdigital: erythema, fissures, scaling, and
maceration in the interdigital spaces of the
toes
• Vesicular: vesicles, bullae, and erosions on
the instep of the foot
• Moccasin: erythema, fissure, and scaling of
the plantar surface of the foot with extension
to the lateral surfaces Fig. 26.16 Tinea versicolor: Hyperpigmented, thin scaly
papules and plaques on the posterior neck of an adolescent
26 Dermatology 865
Diagnosis • Spreads by direct, prolonged, skin-to-skin

• Diagnosis is usually made clinically contact
• KOH preparation will reveal short hyphae
and spores (spaghetti and meatballs) Clinical Presentation
• Pruritus, often more intense at night
Management • Papules, burrows (white-gray thread-like
• Topical antifungals such as selenium sulfide lines), and vesiculopustules
lotion or ketoconazole shampoo • Common locations: wrists, ankles, axillae,
• Oral antifungals such as fluconazole can be waist, groin, palms, and soles
used for persistent or recurrent infections • Infants may present with less common fea-
• Normalization of pigmentation may take months tures such as involvement of the scalp or a
robust hypersensitivity reaction to the mite
characterized by red to brown nodules in the
Onychomycosis trunk, axillae, or groin
• Fungal infection of the nail, usually due to • Clinical diagnosis
dermatophytes such as Trichophyton, • Confirmatory test: skin scraping with mineral
Epidermophyton, or Microsporum oil and use of a microscope to identify the
• Toenails are more affected than fingernails mites, eggs, or feces
• Common in adolescents and adults
Management
Clinical Presentation • All contacts and family members of a child
• Commonly seen with tinea pedis or tinea man- with scabies will require treatment even if
uum (dermatophyte infection of the hands) asymptomatic
• One or multiple nails may be involved • Permethrin 5% cream is first-line treatment;
• Subungual onychomycosis: thickening of the perform two treatment applications spaced
nail with yellow discoloration 1 week apart
• Superficial white onychomycosis: white dis- • Thorough cleansing of all dirty clothing, tow-
coloration with fine powdery scale els, bedding, and car seat covers
Management
• Oral therapy is required for definitive treat- P
ediculosis
ment (see Table 26.2)
• Recurrence is common Background
• Pediculosis capitis (head lice) is caused by
infestation of the human head with Pediculus
humanus capitis (head louse)
INFESTATIONS • Head lice are transmitted via head-to-head
contact or fomites
Scabies • Crab lice, an infestation of the pubic region,
caused by Phthirus pubis (pubic louse), is
Background often sexually transmitted
• Common skin infestation by Sarcoptes scabiei • Louse life cycle
• The microscopic scabies mite burrows into –– Eggs/nits hatch after ~7 days
the upper layer of the skin where it lives and –– A louse reaches adulthood after ~16 days
lays eggs –– An individual louse lives ~30 days
Clinical Presentation • Papules are grouped similar to arthropod bites

• Pruritus • Papules usually occur at sites of bites, but can
• Eggs, nits, and adult lice on the hair shaft also be generalized even to sites where a bite
• For head lice, regional lymphadenopathy did not occur
(cervical, suboccipital) is common
• For crab lice, gray-blue macules may be seen Management
on the abdomen or inner thighs • Symptomatic treatment for pruritus with topi-
cal steroids and antihistamines
Management • Protect against insect bites with clothing and
• Permethrin 1% topical liquid is first-line insect repellant
treatment for head lice and crab lice
• Perform two treatment applications spaced
1 week apart PAPULOSQUAMOUS
• For crab lice, sexual partners need treatment DISORDERS
Psoriasis
Bedbugs
Background
Background • Papulosquamous (elevated lesions with scale)
• Cimex lectularius, the common bedbug, is a condition with tendency to persist or recur for
nocturnal ectoparasite years
• Bite reactions are caused by an immune reac- • An immune-mediated disorder that is likely
tion to the bug’s saliva influenced by both genetics and environment
Clinical Presentation Clinical Presentation
• Erythematous, edematous, pruritic papules • Well-defined papules and plaques that are
on exposed areas of the body pink to deep red with adherent white to silver
• Classically occurs in clusters of three (“break- scale
fast, lunch, and dinner”) • Removal of scale produces pinpoint bleeding
(Auspitz sign)
Management
• Commonly located on the scalp, elbows,
• Topical corticosteroids and antihistamines for
knees, umbilicus, and gluteal cleft
pruritic papules/bites
• Infants may present with involvement of the
• In-home bug treatment by a professional
diaper area
exterminator
• Lesions appear in areas of trauma (Koebner
phenomenon)
Papular Urticaria • Nail pitting, thickening, and discoloration
may be seen
Background
• Common hypersensitivity reaction to insect Management
bites • Topical corticosteroids (first-line of
treatment)
• Pruritic, erythematous, urticarial papules
26 Dermatology 867
• Phototherapy (narrow-band UVB) may be • New lesions appear for 2–3 weeks

used in patients with moderate to severe • Eruption typically resolves over 6–8 weeks
disease
• Systemic therapy, for example, methotrexate Management
or biologics (e.g. TNF-alpha [α] inhibitors), • Reassurance given the self-limited nature
may be used in severe cases • Symptomatic therapy (emollients, antihista-
mines, mild topical corticosteroids) if pruri-
tus is present
Pityriasis Rosea • Differential diagnoses include psoriasis, tinea
corporis, or secondary syphilis
Background
• Self-limited condition of unclear etiology
• Seasonal incidence and clustering of cases LICHENOID DISORDERS
suggest an infectious agent (postulated to be
viral) Lichen Nitidus
Clinical Presentation Background
• Often starts with a “herald patch,” a single • Occurs in school-age children
oval plaque with peripheral scale that can be • Self-limited, benign condition of unclear
mistaken for tinea corporis etiology
• Days to weeks later, numerous oval scaly
papules and plaques appear on the trunk Clinical Presentation
(Fig. 26.17) • Monomorphic, flat-topped, skin-colored papules
• The long axis of these lesions is oriented • Commonly located on the upper extremities,
along lines of cleavage (resembles a Christmas trunk, and genitals
tree) • Lesions appear in areas of trauma (Koebner
• Pruritus is variable phenomenon)
Management
• Spontaneous resolution with time, may take
months to years
• No curative therapy
Lichen Sclerosus
Background
• Predominantly occurs in prepubertal females,
uncommon in males
• Well-demarcated, pink to ivory white, flat-
Fig. 26.17 Pityriasis rosea: Erythematous, scaly, and oval topped papules and plaques that become atro-
papules and plaques follow skin cleavage lines on the neck phic with time
and chest of an adolescent
• The anogenital region is most often affected • IHs slowly improve over years with the
–– Females: Involvement of the vulva and majority of regression occuring by school age
perianal region results in the classic figure- • After resolution, scarring, discoloration, or
of-8 pattern fibrofatty tissue may be left behind
–– Males: Involvement of the glans penis is • Classified as superficial, deep, or mixed
referred to as balanitis xerotica obliterans, IHs
which can be a cause of acquired –– Superficial: bright-red, dome-shaped pap-
phimosis ules, plaques, or tumors; coined “straw-
–– May see purpura within lesions berry hemangioma” (Fig. 26.18)
–– Involvement commonly causes pain, pruri- –– Deep: blue- to purple-hued subcutaneous
tus, and bleeding with urination or nodule or tumor; may appear later and have
defecation a longer growth phase
• Extragenital involvement is often –– Mixed: bright-red papule or plaque with an
asymptomatic underlying subcutaneous component
• Most common complication is ulceration
Management
• Treatment is important as atrophy, and scar- Management
ring can lead to alteration of normal anogeni- • Reassurance for most IHs
tal anatomy • Factors that influence decision to treat: size,
• Ultrapotent topical corticosteroids are first- location, functional impairment (e.g. obstruc-
line treatment tion of vision), and cosmetic impact
• If phimosis is present, circumcision may be • Most effective treatment is oral beta-blockers
required • Other treatment options: topical beta-block-
• May improve at the time of puberty ers, topical/intralesional/oral corticosteroids,
or surgical excision
VASCULAR TUMORS
Infantile Hemangioma (IH)
Background
• Most common benign soft tissue tumor in
childhood
• Unclear etiology
• Risk factors for development of IH include
prematurity, female gender, multiple gesta-
tion, advanced maternal age, preeclampsia,
and placenta previa
• Commonly located on the head and neck
• Most become evident at 2–3 weeks of age
with predominant growth during the first Fig. 26.18 6-month-old female with a superficial infantile
5 months of life hemangioma on the right abdomen
26 Dermatology 869
• Treatment for ulceration: wound care, antibi- Clinical Presentation

otics if secondarily infected, pulsed-dye laser, • Presents with rapid enlargement of the vascu-
and/or oral beta-blockers lar tumor, thrombocytopenia, hemolytic ane-
mia, and coagulopathy
Infantile Hemangioma Variants
• Diffuse neonatal hemangiomatosis Management
–– Association of 5 or more cutaneous IHs • Medical treatments include sirolimus, corti-
with extracutaneous organ involvement costeroids, and chemotherapy agents such as
(usually hepatic) vincristine
–– May see hypothyroidism, anemia, and • Avoid platelet transfusions as they can lead to
thrombocytopenia platelet trapping
• PHACE syndrome
–– Posterior fossa malformation, Hemangioma,
Arterial anomalies, Cardiac anomalies, Eye VASCULAR MALFORMATIONS
abnormalities
–– The hallmark hemangioma is an extensive,
segmental IH of the face • Localized defects of vascular channel forma-
• Lumbosacral hemangiomas tion without associated endothelial
–– Associated with lower body IH, spinal dys- proliferation
raphism, urogenital anomalies, bony defor-
Capillary Malformations
mities, anorectal malformations, and renal
• Nevus simplex
anomalies
–– Common vascular lesion in infants that
–– Image to evaluate for underlying spinal
may be due to persistent fetal circulation
anomalies
–– Also called salmon patch, stork bite (nape
• Beard hemangiomas
of the neck), or angel kiss (forehead/gla-
–– Location on the lower lip, chin, and preau-
bella) (Fig. 26.19)
ricular, mandibular, or neck areas
–– Dull-pink macules and patches usually
–– Extensive IH in the above locations may be
located on the midface, posterior neck, and
associated with upper airway involvement;
scalp
symptoms include cough, biphasic stridor,
–– Facial lesions usually fade by 2 years, but
and hoarse voice
may become prominent with crying or
straining
Kasabach-Merritt Phenomenon • Port wine stain (PWS)
–– Also called nevus flammeus
Background –– Represents a true capillary malformation
• Phenomenon associated with vascular tumors, –– Congenital pink to dark red macules and
specifically kaposiform hemangioendotheli- patches that persist throughout life and
oma or tufted angioma grow in proportion to the child
• Occurs most commonly during the first few –– Stains may darken or thicken with age
weeks of life –– PWSs are usually not associated with
• High mortality rate: 10–30% underlying disorders
a b
Fig. 26.19 Nevus simplex in an infant (a) Erythematous patches on the forehead, glabella, upper eyelids, and upper cutane-
ous lip (b) Erythematous patch on the occipital scalp and neck
• Infants with a large facial PWS involving V1

or multiple trigeminal dermatomes warrant
specialty referral (dermatology, ophthalmol-
ogy, neurology) to evaluate for Sturge-Weber
syndrome
Arteriovenous Malformation
Background
Fig. 26.20 9-month-old female with Sturge-Weber syn-
• Rare, dangerous vascular malformation with
drome with associated glaucoma and seizures (Courtesy of arterial and venous components and arterio-
Sitratullah O. Kukoyi-
Maiyegun, MD, Department of venous shunting
Pediatrics, Paul L. Foster School of Medicine, Texas Tech
University Health Sciences Center, El Paso, Texas) Clinical Presentation
• Cephalic location is most common
–– Sturge-Weber syndrome: association of a • May present with a red patch simulating a
facial port wine stain (usually involving the PWS, a pulsating mass with thrill, or necrosis
distribution of the first branch of the tri- and ulceration
geminal nerve (V1) +/− other trigeminal • Occasional association with cardiac
dermatomes), leptomeningeal angiomato- compromise
sis (usually causing seizures), and
glaucoma (Fig. 26.20) Management
• Ultrasound, MRI, and arteriography can help
Management to confirm the diagnosis
• Pulsed-dye laser can be used to lighten the • Treatment is challenging, but may include
PWS embolization and excision
26 Dermatology 871
HYPERSENSITIVITY REACTIONS
Urticaria
Background
• Type I hypersensitivity reaction with skin
manifestations
• Activation of mast cells leads to degranula-
tion and release of vasoactive mediators such
as histamine, leukotrienes, and
prostaglandins
• Acute urticaria lasts < 6 weeks; chronic urti-
caria lasts > 6 weeks
• The majority of acute urticaria in children is Fig. 26.22 Urticaria multiforme: Erythematous annular
secondary to infection, usually a virus wheals with a dusky center scattered on the back of an infant
Clinical Presentation Management

• Well-circumscribed erythematous pruritic • Reassurance; majority of urticaria will resolve
wheals on the skin and mucous membranes within 2 weeks
(Fig. 26.21) • Symptomatic treatment with non-sedating
• Transient skin lesions; each lesion commonly histamine (H1) blockers such as cetirizine,
lasts less than 12–24 h loratadine, or fexofenadine during the day
• May be polycyclic, annular, or serpiginous; and sedating histamine blockers at night such
annular lesions may be confused with ery- as diphenhydramine or hydroxyzine
thema multiforme • For chronic urticaria, further evaluation is
• Urticaria multiforme describes a morpho- warranted by a dermatologist or allergist
logic subtype with erythematous annular or
polycyclic wheals with a dusky or ecchymotic
center (Fig. 26.22) Cutaneous Lupus Erythematosus (CLE)
Background
• May be an isolated finding or associated with
underlying systemic lupus erythematosus
• Classification includes acute CLE, subacute
CLE, and chronic CLE
• Acute CLE: malar or generalized photodis-
tributed rash, often associated with systemic
disease
–– Erythematous, scaly papules or plaques
involving the nasal bridge and cheeks
(“butterfly rash”); when present on the dor-
Fig. 26.21 2-year-old female with urticaria secondary to a sal hands, the rash typically spares the skin
recent viral infection overlying the joints
• Subacute CLE: uncommon in pediatric • Mild symptoms may be present such as fever,
patients, annular or polycyclic erythematous malaise, myalgia, and arthralgia
plaques involving the upper trunk and upper
extremities, mild systemic manifestations if Management
present • Resolution within 1–4 weeks
• Chronic CLE: can be classified as discoid • If recurrent, may consider prophylactic treat-
lupus or lupus panniculitis; these are rare in ment with acyclovir
children
–– Discoid lupus: well-circumscribed ery-
thematous indurated plaques most com- tevens-Johnson Syndrome (SJS)
S
mon on the face and ears, if untreated can and Toxic Epidermal Necrolysis (TEN)
lead to dyspigmentation and atrophy, may (Table 26.3)
be associated with systemic disease
–– Lupus panniculitis: well-circumscribed • Variants of the same hypersensitivity syn-
indurated subcutaneous papules or nodules drome categorized by the extent of epidermal
most common on the face, upper arms, detachment
thighs, or buttocks; may lead to significant
disfigurement Table 26.3 Differences between Stevens-Johnson syn-
drome and toxic epidermal necrolysis
Management
Stevens-Johnson Toxic epidermal
• Evaluation for underlying systemic disease syndrome necrolysis
especially if other symptoms are present Medications or
• Strict sun protection, topical anti-inflamma- Cause infection Medications
tory agents such as topical corticosteroids, Pattern of Erythematous Erythematous
and occasionally antimalarials (hydroxy- skin lesions macules or papules, macules and papules,
target-like lesions, target-like lesions,
chloroquine) or oral corticosteroids
vesicles and erosions and diffuse
epidermal
detachment
Erythema Multiforme (EM) Mucous Severe mucosal Severe mucosal
membrane involvement of ≥ 2 involvement
Background involvement sites such as the
• Self-limited hypersensitivity reaction with ocular, oral, or
genital mucosa
the majority of cases secondary to herpes Body surface Less than 10% More than 30%
simplex virus area with
• Commonly lasts 1–4 weeks and can be epidermal
recurrent detachment
(%)
• May involve both the skin and mucous
Management Removal of Admission to ICU or
membranes offending agent, burn center, removal
supportive care; of offending drug;
Clinical Presentation systemic treatment is treatment is
• Symmetric, fixed, erythematous targetoid (3 controversial but controversial but
zones of color/concentric circles) papules or may include may include
systemic systemic
plaques often on the distal extremities
corticosteroids, corticosteroids,
• Up to 50% of patients may have mucous IVIG, and TNF-α IVIG, and TNF-α
membrane involvement inhibitors inhibitors
IVIG Intravenous immunoglobulin
26 Dermatology 873
• SJS: < 10% of epidermal loss VIRAL INFECTIONS

• SJS/TEN overlap: 10–30% of epidermal loss
• Toxic epidermal necrolysis (TEN): > 30% of
OF THE SKIN
epidermal loss (Fig. 26.23)
olluscum Contagiosum
M
• Infection (e.g. Mycoplasma) and less com-
monly drugs (see list below), may cause SJS Background
• Majority of cases of TEN are secondary to • Common viral infection of the skin in young
drugs—allopurinol, antiepileptic agents (car- children
bamazepine, lamotrigine, phenytoin), • Caused by a DNA poxvirus called the
NSAIDs, sulfonamides, barbiturates, and Molluscum contagiosum virus
penicillin
• Skin-colored to pink, domed, pearly papules
with central depression (Fig. 26.24)
• Lesions can trigger a surrounding dermatitis
(“molluscum dermatitis”)
• Involvement is often more extensive in
patients with atopic dermatitis
Management
• Treatment is not necessary as spontaneous
resolution occurs in several months to years
• Potential therapeutic options: watchful waiting,
Fig. 26.23 Toxic epidermal necrolysis intralesional candida antigen injections, topical
a b
Fig. 26.24 Molluscum contagiosum (a) School-age child extremity. There are two erythematous, indurated mollus-
with molluscum contagiosum on the anterior neck (b) cum lesions secondary to immune reaction
Toddler with molluscum contagiosum of the lateral lower
therapies (cantharidin, imiquimod), or destruc- • Can spread via sexual transmission or benign
tive modalities (liquid nitrogen, curettage) transmission (autoinoculation, vertical trans-
• If pruritic, the molluscum dermatitis can be mission, fomites)
treated with twice-daily application of a low-
potency topical corticosteroid Clinical Presentation
• Skin-colored, soft, verrucous papules in the
anogenital region
Verruca Vulgaris
Management
Background • Be mindful of potential for sexual transmis-
• Common viral infection caused by the human sion/screen when appropriate
papillomavirus (HPV) • Potential therapeutic options: watchful waiting,
topical therapies (podophyllin, trichloroacetic
Clinical Presentation acid, imiquimod), and destructive modalities
• Single or multiple, skin-colored, verrucous (cryotherapy, electrodesiccation, curettage)
papules
• Often located on the hands, but may be pres-
ent on any skin surface (Fig. 26.25) BACTERIAL INFECTIONS
Management
OF THE SKIN
• No specific antiviral therapy
I mpetigo
• Potential therapeutic options: watchful waiting
(often spontaneously resolve), topical salicylic Background
acid, liquid nitrogen, immunotherapy (imiqui- • Primarily caused by S. aureus and sometimes
mod, candida antigen injections, oral by group A beta-hemolytic streptococci
cimetidine) (GABHS)
• Two forms: bullous and non-bullous
• Non-bullous impetigo is more common
Condyloma Acuminatum
Background
• Non-bullous form often presents with honey-
• Manifestation of HPV infection in the ano-
colored scabs formed from dried serum
genital region
Fig. 26.25 (a) Child with

multiple verrucae on the
a b
dorsal hand. (b) Child with
periungual verruca vulgaris
26 Dermatology 875
• Favors the flexural areas and periorificial

skin; involvement around the mouth can
present with crusting and radial
fissures
• Nikolsky sign: Firm pressure at the edge of
the blister causes further progression/lateral
spread of the cleavage plane
• Usually associated fever and malaise
Management
• Hospitalization for systemic anti-staphylo-
coccal antibiotic, wound care, pain control,
fluid and electrolyte management
Cellulitis
Background
• Acute infection of the skin and subcutane-
ous tissues most often due to S. aureus or
GABHS
• Usually caused by trauma to the skin
Fig. 26.26 Young female child with impetigo on the back
• Local pain, tenderness, swelling, and ery-
secondary to Staphylococcus aureus
thema that progresses rapidly and may involve
• Bullous form is characterized by flaccid bul- large areas of the skin
lae and shallow erosions surrounded by resid- • Systemic manifestations include fever, chills,
ual blister roof (Fig. 26.26) malaise, lymphangitis, and bacteremia
• Erysipelas is a superficial form of cellulitis,
Management classically caused by GABHS, that has prom-
• Topical anti-staphylococcal antibiotic for mild inent lymphatic involvement
cases
• More extensive cases warrant wound culture Management
and systemic antibiotics • Targeted systemic antibiotics that cover for
both S. aureus and GABHS
• Hospitalization may be required for seriously
Staphylococcal Scalded Skin ill patients or those not responding to oral
Syndrome (SSSS) antibiotics
Background
• Blistering skin disease caused by an exfolia- I ntertrigo
tive toxin produced by S. aureus
Background
• Most common in neonates or young children
• Rubbing and occlusion of skin surfaces
Clinical Presentation results in erosions and skin irritation
• Prominent erythema, fragile blisters, and sub- • May become secondarily infected with bacte-
sequently denuded skin; skin is painful ria or Candida species
Clinical Presentation • Syndromic forms of albinism include

• Erythematous and superficial erosions located Hermansky-Pudlak, Griscelli, and Chediak-
in skinfolds Higashi syndromes
Management Clinical Presentation

• Apply adsorbent powder to keep affected • Nonsyndromic forms of OCA:
areas dry –– Affected persons have light skin, hair, and
• Severe cases may benefit from low-potency eyes regardless of ethnic background
topical corticosteroids –– Dependent upon the OCA type, eyes, hair,
• Antifungal therapy if Candida infection or and skin vary in pigmentation; some
antibiotics if bacterial infection is suspected develop lentigines/pigmented nevi; risk of
cutaneous malignancy varies
–– Eye manifestations: photophobia, strabis-
Necrotizing Fasciitis mus, nystagmus, and decreased visual
acuity
Background • Syndromic forms of OCA:
• Infection of the deeper subcutaneous tissues –– Hermansky-Pudlak syndrome: pigment
and fascia dilution of the skin and eyes, hemorrhagic
• Several bacteria can cause necrotizing fasci- diathesis secondary to platelet dysfunction,
itis (GABHS, S. aureus, Clostridium perfrin and complications such as granulomatous
gens, Bacteroides fragilis, Aeromonas colitis, pulmonary fibrosis, cardiomyopa-
hydrophila) thy, or renal failure
–– Griscelli syndrome: pigment dilution of the
skin with silvery hair; different types may
• Painful, extensive, rapidly progressive necro-
manifest immune or neurologic dysfunction
sis and gangrene of the skin and underlying
–– Chediak-Higashi syndrome: pigment dilu-
tissue
tion of the skin and eyes with silvery hair,
• Patients are usually ill and have a high tem-
pyogenic infection (S. aureus, GABHS,
perature and toxic appearance
and Streptococcus pneumoniae), bleeding
Management diathesis, and neurologic deterioration
• Hospitalization for broad-spectrum antimi- with age
crobial therapy, surgical debridement, and
Management
pain control
• Strict sun protection and evaluation by a der-
matologist and ophthalmologist
• If concerned for a syndromic form of OCA,
DISORDERS OF PIGMENTATION evaluation by a hematologist and/or neurolo-
gist may be appropriate
Albinism
Background
Pityriasis Alba
• Absent or decreased melanin biosynthesis of
the eye, hair follicles, and skin • Nonspecific dermatitis followed by post-
• Includes syndromic and nonsyndromic forms inflammatory hypopigmentation
of albinism • Small, poorly defined, hypopigmented, scaly
• Nonsyndromic forms include oculocutaneous macules and patches predominantly on the
albinism (OCA) types I–VII face
26 Dermatology 877
• Encourage sun protection and moisturization • Development of lesions commonly begins on

of the skin the face, dorsal hands, and neck; other sites of
• If erythema is present, a mild topical cortico- involvement are body folds (axillae, groin),
steroid or topical calcineurin inhibitor may be orifices (eyelids, nostrils, genitals, perianal
used skin), and bony prominences (elbows, knees,
skins)
• White hair can be seen
Vitiligo • Halo nevi are common in prepubertal chil-
dren (pigmented nevi with surrounding
Background depigmentation)
• An immune-mediated disorder leading to • Pigmentation returns from the hair follicle as
depigmentation of the hair, skin, and mucosa small, “freckle-like” spots within the area of
• Can be characterized as focal, segmental, or depigmentation
generalized
• Family history of vitiligo is present in 30% of Management
patients as well as an increased incidence of • Sun protection to affected areas
autoimmune disease • Repigmentation can be difficult but is most
successful on the head and neck
Clinical Presentation • Treatments include anti-inflammatory agents
• May be partially or completely depigmented such as topical corticosteroids, topical calci-
macules or patches (Fig. 26.27) neurin inhibitors, and NB-UVB phototherapy
Post-inflammatory Hypo-/
Hyperpigmentation
Background
• Self-limited dyspigmentation preceded by
inflammatory dermatoses
• Pathogenesis of both is unclear
• Post-inflammatory hypopigmentation: ill-
defined hypopigmented macules and
patches
• Post-inflammatory hyperpigmentation: ill-
defined hyperpigmented macules and patches
Management
• Provide reassurance
• Sun protection as this becomes more cosmet-
ically apparent with sun exposure
• Self-limited and will resolve over months to
years
• Treatment of preceding inflammatory derma-
Fig. 26.27 Vitiligo: Depigmented patches on the lower tosis if appropriate
extremity of a child
Nevus of Ota
• Unilateral, irregular brown to blue-gray pigmen-
tation of the face in the distribution of the first
and second divisions of the trigeminal nerve
• Two-thirds of patients have associated dyspig-
mentation of the sclera of the ipsilateral eye
• May darken at puberty and have a speckled
appearance
• Associated with glaucoma (10% of patients)
and melanoma of the eye, skin, and brain
(rare)
• Monitoring by dermatology and ophthalmol-
ogy; if there is a cosmetic concern, may treat Fig. 26.28 Dermal melanocytosis: Blue-gray patch on the
with laser therapy lumbosacral area of an infant
Nevus of Ito
• Unilateral, irregular brown to blue-gray pig-
mentation of the neck, shoulder, supracla-
vicular and deltoid areas, and/or upper arm
skin
• May darken at puberty
• If a cosmetic concern, may treat with laser
therapy
Dermal Melanocytosis
• Commonly referred to as Mongolian spots Fig. 26.29 Café-au-lait spots. Scattered tan macules and
• Ill-defined brown to blue-gray pigmentation patches on the abdomen of a child
commonly on the lumbosacral skin and but-
tocks (Fig. 26.28) • If more than 5 CALMs are present, consider
• Present at birth and fades with time, occa- an underlying genetic condition such as
sionally present in adulthood neurofibromatosis or Legius syndrome
• Most common in dark-skinned persons • Consider McCune-Albright syndrome if a
• If extensive and numerous, consider underly- large, unilateral CALM is present in a derma-
ing lysosomal storage disorders tomal distribution
Café-au-Lait Macules (CALMs) MELANOCYTIC TUMORS

• Oval to round, tan to brown macules or C ongenital Melanocytic Nevi (CMN)
patches present at birth or shortly thereafter
(Fig. 26.29) • Lesions with an increased number of melano-
• Present in approximately 30% of normal chil- cytes, usually present at birth or within the
dren, can occur anywhere on the body first year of life (Fig. 26.30)
26 Dermatology 879
• May develop from a preexisting mole or may
be a new growth
• Features that should raise concern for mela-
noma include the following:
–– Asymmetry, irregular borders, multiple
colors, large or enlarging diameter, and
evolution (ABCDE)
–– An enlarging pink +/− bleeding papule
–– Any “ugly duckling” nevus (a nevus that
differs significantly in clinical appearance
from a child’s other nevi)
Management
Fig. 26.30 Congenital melanocytic nevus: Homogenous
dark-brown nevoid plaque on the trunk of a child • Early detection and prompt referral to a
dermatologist
• Education regarding the risks of sun expo-
• Classification is based upon the projected sure and discussion of sun protective
largest diameter in adulthood: measures
–– Small: < 1.5 cm • Short-term effects of sun exposure: visible
–– Medium: 1.5–19.9 cm damage to the skin including sunburn, tan-
–– Large: > 20 cm ning, and freckles
• Exact risk of melanoma is debatable, how- • Long-term effects of sun exposure: wrinkles,
ever, large CMN carry a greater risk than age/sun spots, and skin cancer
small or medium CMN • Protective measures: sun avoidance, sun-pro-
• Large CMN of the head, neck, or back, espe- tective clothing (including wide-brimmed
cially those with multiple “satellite” nevi, are hats), and broad-spectrum, SPF30+
risk factors for neurocutaneous melanosis sunscreen
(proliferation of melanocytes in the central • Lifetime practice of sun avoidance and sun-
nervous system that has the potential to cause screen use decreases the lifetime risk of UV
neurologic symptoms or develop melanoma) light-induced skin cancers by ~80%
• Treatment must be individualized based on
CMN site, size, and evolution
• All need clinical monitoring and education
regarding sun protection DERMAL TUMORS
Granuloma Annulare (GA)
Melanoma
• Common in school-age children
Background • Pathogenesis of GA is unknown
• Potentially a fatal form of skin cancer • Skin-colored, non-scaly papules or plaques
• Rare in children, especially prior to puberty in a ring-like distribution on the dorsal
• Risk factors include sun exposure, family his- wrists, hands, ankles, and feet (Fig. 26.31)
tory of melanoma, numerous nevi (> 50–100), • May be mistaken for tinea corporis
large CMN, immunosuppression, and fair skin • No effective treatment spontaneous resolu-
tion within months to years
Mastocytosis • Urticaria pigmentosa: multiple red-brown

macules and papules with a widespread dis-
Background tribution; Darier sign and bullae can be seen
• Group of disorders characterized by the accu- • Diffuse cutaneous mastocytosis: uncommon;
mulation of mast cells within the skin and diffuse mast cell infiltration of the skin;
potentially other organs causes reddish-brown discoloration, skin
• Cutaneous variants common in pediatrics thickening, and numerous blisters
include mastocytomas, urticaria pigmentosa, • Systemic disease: itching, flushing, vomiting/
and diffuse cutaneous mastocytosis (Fig. 26.32) diarrhea/abdominal pain, respiratory distress
Clinical Presentation Management

• Mastocytomas: solitary or multiple skin-col- • Symptomatic treatment with non-sedating and
ored to yellow-orange papules or plaques; sedating histamine (H1) receptor antagonists
become urticarial-like when rubbed (Darier • If GI symptoms are present, consider treat-
sign); vesicles or bullae can also be seen ment with cromolyn sodium
• Localized forms of the disease often improve
with age
• If vesicles or bullae are present, a topical cor-
ticosteroid can be applied
• Avoid mast cell triggers: certain medications
(e.g., NSAIDs), local anesthetics (e.g., tetra-
caine), general anesthesia (e.g., d-tubocura-
rine), iodine-containing contrast, and venoms
Dermoid Cyst
• Nontender, mobile, subcutaneous nodule
most common along the orbital ridge
Fig. 26.31 4-year-old boy with granuloma annulare • Small percent of dermoid cysts or sinuses are
(Courtesy of Sitratullah O. Kukoyi-Maiyegun, MD, located in the midline and require imaging to
Department of Pediatrics, Paul L. Foster School of Medicine, rule out extension to the CNS
Texas Tech University Health Sciences Center, El Paso,
Texas)
• Treatment includes surgical excision
HAIR DISORDERS
Alopecia Areata
Background
• Autoimmune, nonscarring hair loss disorder
in children and adults
Fig. 26.32 Mastocytosis: Scattered yellow-brown plaques, • Sudden appearance of circular areas of hair
some with associated erythema on the trunk of an infant loss, most common on the scalp (Fig. 26.33)
26 Dermatology 881
Telogen Effluvium
• Most common form of hair loss in children
• Diffuse thinning of hair secondary to a
stressful event; examples include an illness,
surgery, childbirth, or medication change
• Hair loss is seen ~6 to 16 weeks following
stressor
• Reassurance; hair regrowth occurs over
months
Fig. 26.33 Alopecia areata: Well-defined patches of alope- Anagen Effluvium

cia with no associated erythema or scale
• Hair loss secondary to the reduction of hair
• Classified as localized, ophiasis (band-like shaft production during the growth (anagen)
hair loss of the temporal and occipital scalp), phase
totalis (loss of all scalp hair), and universalis • Commonly occurs in children receiving che-
(loss of all scalp and body hair) motherapy or radiation
• Appearance of underlying skin is smooth and
commonly without erythema
• Nail pitting can be seen Traction Alopecia
Management • Hair loss secondary to excessive pulling (tight

• Reassurance; spontaneous hair regrowth usu- ponytails, braids, etc.), most prominent at the
ally occurs with localized disease margins of the hairline
• Treatments include topical or intralesional • If untreated, may lead to scarring and perma-
corticosteroids, topical minoxidil, and topical nent hair loss
immunotherapy (e.g. squaric acid) • Treatment: relaxed hairstyles and avoidance
of other stressors to the hair (such as heat and
chemicals)
Trichotillomania
• Self-induced pulling and breakage of the hair, GENODERMATOSES
most common on the scalp
• Associated with psychological distress, habit- E pidermolysis Bullosa (EB)
ual pulling (e.g. prior to sleeping, television
watching), or compulsive behavioral Background
disorders • Group of genetic disorders characterized by
• Characterized by irregular patches of hair skin fragility and bullous lesions secondary to
loss with hair of varying lengths friction or trauma
• Treatment can be difficult; strong physician, • Genetic mutations occur within components
patient, and parent relationship is important; of the basement membrane zone of the skin
behavioral modifications; psychiatric therapy • Major subtypes of EB include EB simplex,
if appropriate junctional EB, and dystrophic EB
Clinical Presentation • Mutation in the nuclear factor-kB essential

• EB simplex modulator (NEMO, IKBKG)
–– Blister formation on the palms and soles
secondary to trauma Clinical Presentation
–– Heals without scarring • Cutaneous lesions appear in the first few
• Junctional EB weeks of life
–– Can range from mild to severe • 4 stages of cutaneous lesions that may not
–– Generalized severe junctional EB: 50% appear in sequential order or can overlap
mortality rate in early childhood; blistering –– Stage 1: crops of inflammatory vesicles or
occurs on the skin, oral mucosa, esopha- pustules that occur in a whorled pattern
gus, and airway; perioral granulation tis- (blaschkoid distribution)
sue, dental enamel hypoplasia, growth – – Stage 2: verrucous papules most prominent
retardation, and scarring on the extremities, hands, and feet
–– Other variants of junctional EB include –– Stage 3: brown to blue-gray macules and
localized, junctional EB with pyloric atre- patches; pigmentation may persist for
sia, and generalized intermediate junc- years
tional EB – – Stage 4: hypopigmented and atrophic
• Dystrophic EB plaques most common on the trunk and
–– Dominant dystrophic EB: Blisters on the extremities
skin result in scarring, mild mucous mem- • Scarring alopecia and nail dystrophy can be
brane involvement, and nail dystrophy seen
–– Recessive dystrophic EB (RDEB): life- • Dental anomalies include delayed dentition,
threatening bullous disease with severe partial anodontia, and conical/pegged shaped
scarring leading to fusion of the fingers and teeth
toes, esophageal involvement with resul- • ~30% of patients have CNS involvement,
tant stenosis, dental caries, nail dystrophy, commonly seizures
and growth retardation • ~35% of patients have ocular disease such as
–– RDEB patients have an increased risk of strabismus, cataracts, optic atrophy, and reti-
cutaneous squamous cell carcinoma which nal neovascularization/detachment
can lead to death
Management
Management • Cutaneous lesions will clear and do not
• Wound care for skin fragility and skin require treatment
blistering • Early ophthalmologic evaluation is important
• Evaluation by a multidisciplinary team is to discover and treat retinal disease if present
important • Neurologic evaluation if seizures or develop-
mental delay is present
Incontinentia Pigmenti
Ectodermal Dysplasia
Background
• X-linked dominant disorder that affects the Background
eyes, teeth, CNS, and skin • ~150 inherited disorders characterized by
• Approximately 65% of cases are sporadic abnormalities of ectoderm-derived tissues
mutations (such as the skin, hair, teeth, and nails)
26 Dermatology 883
• Select disorders within this group include the • Moisturization is key; emollients containing lac-
following: tic acid or urea are helpful for reducing scaling
–– Hypohidrotic ectodermal dysplasia
–– Hidrotic ectodermal dysplasia
–– Ectrodactyly-ectodermal dysplasia-cleft MISCELLANEOUS
lip/palate (EEC) syndrome
–– Ankyloblepharon-ectodermal defects-cleft L angerhans Cell Histiocytosis (LCH)
lip/palate (AEC) syndrome
Background
Clinical Presentation • Infiltration of Langerhans cells, bone mar-
• Hypohidrotic ectodermal dysplasia: reduced row-derived antigen-presenting cells, into
or absent sweating, conical teeth, characteris- various organs
tic facies (frontal bossing, saddle nose, thick/ • Unknown pathogenesis
everted lips), sparse hair, often associated • Skin and bones are the most commonly
atopy involved organs; skin changes are usually the
• Hidrotic ectodermal dysplasia: nail changes, presenting complaint
thin hair, thickening of the palms and soles; • Involvement may be unifocal, multifocal, or
teeth and sweating are normal disseminated; extensive disease has a poor
• EEC: ectrodactyly (split hand/foot deformi- prognosis
ties), ectodermal dysplasia (sparse hair, teeth
abnormalities), clefting, abnormalities of the Clinical Presentation
lacrimal tract • Skin:
• AEC: ankyloblepharon (strands of tissue –– Classically a red, scaly dermatitis of the
between the eyelids), ectodermal defects scalp, axillae, and diaper area that can
(erosions of the scalp, sparse/fine hair, nail mimic seborrheic dermatitis; resistant to
changes, hypohidrosis), clefting standard treatments for seborrheic dermati-
tis (distinguishing feature)
Management –– Red to brown papules that may have over-
• No curative therapy lying hemorrhage, erosion, or crust
• Multidisciplinary support required • Bone: pain and swelling caused by lytic
• Supportive measures such as artificial sweat lesions, usually affects the skull or long bones
for patients with hypohidrotic ectodermal • CNS: diabetes insipidus, hyperreflexia, cra-
dysplasia and wound care for scalp erosions nial nerve defects
of patients with AEC • Other organ systems that may be involved
include the lungs (pulmonary dysfunction),
spleen (splenomegaly), bone marrow (cyto-
Ichthyosis Vulgaris penias), lymph nodes (lymphadenopathy),
etc
• Most common form of ichthyosis, shows
autosomal semi-dominant inheritance Management
• Characterized by gray, polygonal scales com- • Patients with suspected LCH require an
monly involving the lower extremities extensive workup that often includes imag-
• Groin and flexural areas are usually spared ing, laboratory studies, and biopsy; referral
• Hyperlinear palms and associated atopy often to hematology and dermatology is
seen important
• Degree of therapy is driven by extent of • Mode of injury to the skin can vary: scratch-
involvement ing, cutting, picking, burning, etc
• Skin-limited disease does not require therapy, • Face, upper trunk, and upper extremities are
but can be treated with topical corticosteroids most often involved; pay attention to the
• Vital organ dysfunction may warrant aggres- handedness of the patient; linear, geometric,
sive systemic therapy with corticosteroids and well-demarcated areas of skin injury are
and chemotherapy seen
• Long-term monitoring • Treatment can be difficult; strong physician,
patient, and parent relationship is important;
behavior modifications; psychiatric therapy if
Acanthosis Nigricans appropriate
• Presents as velvety-brown plaques within

skinfolds such as the neck and axillae PEARLS AND PITFALLS
(Fig. 26.34)
• Pathogenesis unknown earls
P
• May be associated with obesity, insulin resis-
tance, or malignancy (rare in pediatrics) • The pustules of erythema toxicum contain
• Treatment is difficult; weight reduction and eosinophils, while the pustules of transient
healthy lifestyle if secondary to obesity or insu- neonatal pustular melanosis contain
lin resistance; topical keratolytics or topical neutrophils
retinoids may improve cosmetic appearance • If erythema, vesicles, or bullae occur in a line,
consider an outside cause such as rhus derma-
titis/poison ivy
Factitious Disorders • Bites in clusters of three (“breakfast, lunch,
and dinner”) are suggestive of bed bugs
• Self-inflicted lesions on the skin secondary to • Lichen sclerosus of the anogenital region
psychological stressors, may be associated necessitates aggressive therapy with high-
with secondary gain potency topical steroids
• Infantile hemangiomas have a characteristic
growth pattern (rapid growth during the first
~5 months of life and slow involution over years)
• A nevus simplex will fade with time, but a
port wine stain will persist for life and may
become darker or thicker
• Erythematous, scaly papules or plaques
involving the nasal bridge and cheeks (“but-
terfly rash”) should raise concern for acute
CLE
• A lesion of urticaria will last < 24 h; a lesion
of erythema multiforme will last for days to
weeks
• The Nikolsky sign is seen with both SJS and
SSSS; SJS involves < 10% of the skin (espe-
Fig. 26.34 Acanthosis nigricans in a teenager with type II cially the trunk) and > 2 mucosal sites, whereas
diabetes mellitus SSSS favors the flexures and periorificial skin
26 Dermatology 885
• Alopecia areata causes complete hair loss • Granuloma annulare is red and annular but
(hair falls out by the roots) with underlying lacks scale, thus distinguishing it from tinea
smooth skin corporis
• The first sign of NF is usually CALMs; the • LCH can mimic seborrheic dermatitis (con-
first sign of TS is usually hypomelanotic sider LCH in cases of treatment-resistant seb-
macules orrheic dermatitis)
• Ectodermal dysplasias commonly involve the
skin, hair, teeth, and nails Acknowledgement The authors gratefully
acknowledge the contributions of Sitratullah
Olawunmi Kukoyi-Maiyegun, MD, Department of
Pitfalls Pediatrics, Paul L. Foster School of Medicine,
Texas Tech University Health Sciences Center, El
• Atopic dermatitis in the diaper area is uncom- Paso, Texas, to the first edition of this chapter,
mon; rashes in the diaper area should prompt some images from which have been incorporated
consideration of irritant diaper dermatitis, into this edition as well.
seborrheic dermatitis, psoriasis, acrodermati-
tis enteropathica, LCH, and skin infections
(such as candida)
• Facial angiofibromas of TS can be mistaken Suggested Reading
for acne vulgaris
• Periorificial dermatitis is made worse by use Browning JC. An update on Pityriasis rosea and
of topical or inhaled corticosteroids other similar childhood exanthems. Curr Opin
• Topical antifungal therapy is inadequate for Pediatr. 2009;2(4):481–5.
onychomycosis and tinea capitis; oral anti- Crespo-Erchiga V, Florencio VD. Malassezia
fungal therapy is necessary for clearance yeasts and pityriasis versicolor. Curr Opin Infect
• Scabies is not adequately treated unless all Dis. 2006;19(2):139–47.
household family members are treated at Eichenfeld LF, Frieden IJ. Neonatal and infant
the same time (even if they are dermatology. 3rd ed. Philadelphia: Elsevier
asymptomatic) Saunders; 2015.
• The herald patch of pityriasis rosea can mimic Johr RH, Schachner LA. Neonatal dermatologic
an isolated patch of tinea corporis challenges. Pediatr Rev. 1997;18(3):86–94.
• Not all infantile hemangiomas occur in iso- Krowchuk DP, Mancini AJ, editors. Tinea versi-
lation; 5+ infantile hemangiomas, segmen- color. In: Pediatric dermatology a quick refer-
tal facial hemangiomas, or large ence guide. 2nd ed. Elk Grove Village: American
hemangiomas of the lower body or lower Academy of Pediatrics; 2012. p. 255–60.
face/neck can have important associations Maverakis E, Fung MA, Lynch PJ,
(liver hemangiomas, PHACE syndrome, Draznin M, Michael DJ, Ruben B, Fazel
spinal abnormalities, and airway hemangio- N. Acrodermatitis enteropathica and an
mas, respectively) overview of zinc metabolism. J Am Acad
• Urticaria can have a dusky center (“urticaria Dermatol. 2007;56(1):116–24.
multiforme”); this is different from erythema Morelli JG. The skin: diseases of the neo-
multiforme where lesions are targetoid with 3 nate. In: Kliegman RM, Stanton BF, St.
zones of color Geme III JW, Schor NF, Behrman RE, edi-
• Molluscum contagiosum can trigger a sur- tors. Nelson textbook of pediatrics. 19th ed.
rounding dermatitis that mimics atopic Philadelphia: Elsevier/Saunders Elsevier;
dermatitis 2011a. p. 2218–20.
Morelli JG. The skin: disorders of the hair. In: Paller AS, Mancini AJ. Hurwitz clinical pediat-
Kliegman RM, Stanton BF, St. Geme III JW, ric dermatology. 5th ed. Philadelphia: Elsevier
Schor NF, Behrman RE, editors. Nelson text- Saunders; 2016.
book of pediatrics. 19th ed. Philadelphia:
Elsevier/Saunders Elsevier; 2011b. p. 2289–93.
Psychosocial Issues and Child Abuse
27
FAMILY AND ENVIRONMENTAL Table 27.1 Usual and unusual grief reaction at different
ages
ISSUES Unusual grief
Age Usual grief reaction reaction
Death Preschool Separation anxiety, Persistence of
decreased appetite, symptoms
• Understanding of death and expression of grief irritability, and regression > 6 months
are determined by chronological age and lev- < 6 months
School-age Poor academic
Persistence of
els of cognitive development. These are cou-
performance, school
symptoms
pled with circumstances of death as well as the phobia, and physical
> 3 months
family’s cultural and religious background. complaint < 3 months
• Levels of cognitive and behavioral develop- Adolescent Somatic complaint
Increased high-
ment differ by age: < 3 months
risk behavior,
withdrawal from
–– Children < 2 years: sensorimotor stage. peer interaction
–– Children 2–6 years: preoperational stage.
–– Children 6–10 years: concrete operational
stage. The Concept of the Stages of Grief Introduced
–– Adolescents: formal operational stage. by Kubler-Ross
• Grief reactions occur in different domains
that include the emotional, cognitive, physi- • Denial
cal, and social domains (Table 27.1): • Anger
–– Usual expressions of grief include repeated • Bargaining
questioning, somatic complaints, regres- • Depression
sive behaviors, separation anxiety, school • Acceptance
phobia, or academic difficulty.
Management
–– Adolescents may present with increased
• When death is anticipated, information about
high-risk behavior with drugs, alcohol,
expectations and effective counseling will
delinquency, or precocious sexual activity.
help family bereavement.
• A dying child benefits from open communi-
cation about death.
S. O. Kukoyi-Maiyegun (*)
e-mail: sitratullah.maiyegun@ttuhsc.edu

888 S. O. Kukoyi-Maiyegun
• Encourage family members to be with their Management

child after death, e.g., holding, rocking, or • Consistency in parenting techniques and dis-
bathing their child’s body. cipline as a way to promote stability and
• Siblings may help in funeral planning, e.g., predictability.
choosing the burial clothing. • Pediatrician should avoid taking sides or
• The pediatrician can provide counseling and overidentifying with one parent vs. another.
support by listening to and communicating • Report to a child protective service (CPS) if
well with the family. there is suspicion of abuse or neglect or sig-
• Scheduling an appointment with the family nificant parental substance abuse.
about 1 month after the death to evaluate the • Provide counseling and consult to appropri-
family’s coping ability. ate resources in cases of significant parental
• Pediatricians need resources and support mental health problems.
within the medical community to help cope • Refrain from providing legal advice and refer
most effectively with the death of a patient. those questions to the parent’s legal counsel.
• Monitor the emotional and behavioral adjust-
ment of children of divorced parents.
Divorce • Parents are encouraged to speak positively
Long-Lasting Effects of Divorce or Separation about each other and to avoid blaming one
on the Child and the Family another for the divorce in front of children.
• Academic underachievement, depression, • Encourage agreement between parents and
delinquency, and high-risk behaviors such as coordination of parenting plans to avoid esca-
drug use and early sexual activity. lation of conflict and improve co-parenting
• Families may experience increased financial cooperation, thus saving significant legal
difficulties. fees.
• Children exposed to high-conflict parental
interactions are significantly more likely to
exhibit externalizing behavioral problems, Discipline
emotional dysregulation, and decreased aca-
demic performance. • Disciplinary approaches depend on the child’s
developmental stage.
Protective Factors That May Increase the • Time-out for negative behavior is an effective
Likelihood of Long-Term Positive Psychological strategy for age 1 year to early adolescence.
Adjustment • Time-out will be effective if parents also pro-
• Parents must allow adequate time for children vide time-in with short nonverbal physical
to adjust to divorce before forming any new contact on a frequent basis for acceptable
relationship. behavior.
• The slow introduction to a new partner. • Extinction is a method by which the parent
• Cooperative co-parenting is most helpful in withdraws all attention (and thus reinforce-
children’s adjustment to divorce. ment) from a child’s undesirable behavior.
• Structured routine provides stability, helps This may initially increase the intensity of the
with both short and long-term adjustment, undesirable behavior (extinction burst), but
and leads to better outcomes. with parental perseverance, the undesirable
• Regular schedule with flexibility for change. behavior will diminish.
27 Psychosocial Issues and Child Abuse 889
• In planned ignoring, the parents gradually • The ideal time to prepare for supportive rela-
ignore the child’s behavior; this method tends tionships between siblings is during the
to take longer but does not lead to an increased months prior to the new baby’s arrival.
undesirable behavior. • Referral to a therapist may be considered if
• Family chip system (ages 3–7 years): the behavior continues to be challenging and
–– Fake coin currency can be used as a chip. unresponsive to initial parental interventions.
–– A child earns chips for desired behavior,
e.g., brushing teeth or going to school
without a tantrum. eparation Anxiety and School
S
–– The child can watch television (TV) or Refusal
play a video game in exchange for chips.
–– A child loses chips for undesired behavior, General Considerations
e.g., fighting with a sibling, yelling, etc. • Separation anxiety disorder is one of the most
The child may not play video games or common causes of school refusal.
watch TV. • Separation anxiety is developmentally appro-
priate in the preschool child and during the
first few months of school in kindergarten or
Sibling Rivalry first grade.
• School refusal related to anxiety differs from
• Sibling rivalry and jealousy are common. conduct problems and subsequent truancy.
• Youth who exhibit truancy generally do not
Causes report other symptoms of anxiety or issues of
• Unequal amounts of parents’ attention, disci- separation from parents.
pline, and responsiveness
• Family stress Treatment
• Birth order • In school refusal due to separation anxiety
• Birth of a new sibling disorder, the child needs to go back to the
• Personality school environment as soon as possible.
• Children very close in age and of the same • Decrease in stress, proper sleep hygiene,
gender healthy eating, regular exercise, predictable
• 1 or both children intellectually gifted routine, and social supports.
• Cognitive behavioral therapy.
Management • Pharmacotherapy: selective serotonin reup-
• Children should initially be allowed to resolve take inhibitors (SSRIs).
their differences on their own.
• Parents need to intervene in the case of
physical or verbal abuse; the fighting sib- Media
lings should be separated and told violence
is not allowed. Impact of Mass Media
• Parents should focus on the individual needs • Pediatricians should routinely ask about the
of each child, giving each the time and atten- amount of recreational screen time.
tion necessary to feel loved and secure. • Children younger than 2 years of age should
• Parents should be vigilant to favoritism. not watch television (TV).
• Solitary TV viewing should be discouraged Legal Issues

in young children. • Usually arranged through the government or
• Limiting TV viewing, including other forms a social service agency.
of screen time, to 2 h/day or less for all • All legal decisions are made by the state
children. through the family court and child protection
• Parents should supervise the proper use of the agency; the foster parent is responsible for
internet and social networking sites. the day-to-day care.
• Media can be beneficial in enhancing learn- • Legal guardians/foster parents can consent to
ing, health, and connection with others. medical treatment for children under their
• Discourage parents from having a TV or care.
internet-connected device in a child’s bed-
room, as it causes sleep disturbance (sleep Management
latency prolongation) and increases the risk • Within 72 h of foster care placement, evaluate
of adverse effects from media. these children for abuse, neglect, acute infec-
• Education of parents on links between TV tions, mental health issues, and immediate con-
viewing, obesity, and diminished academic cerns related to chronic medical conditions.
performance. • Within 30 days of entrance into foster care,
the child should be evaluated for any physi-
Potential Negative Effects of TV Viewing on cal, mental, developmental, and dental prob-
Children lems in order to develop a coordinated
• Increased aggressive behavior, inattention, management.
acceptance of violence, obesity, substance • Family-based foster care is generally pre-
use, sleep problems, obscured distinction ferred to other forms of out-of-home care.
between fantasy and reality, trivialization of
sex and sexuality Complications
• Increased passivity, obesity, and risk of sui- • Children in foster care suffer more physical,
cidal behavior psychological, and cognitive or mental health
• Less time spent on healthier activities and problems.
increased risk of adverse effects from media
Immigrants and Internationally
Foster Care Adopted Children
Background General Considerations
• Foster care is a system in which a minor is • Depending on their country of origin, interna-
placed into a ward, a group home, or the pri- tional adoptees may be at risk of certain infec-
vate home of a state-certified caregiver who is tious diseases, particularly parasitic infections.
compensated for expenses. • Children adopted from institutional or
• Parental neglect is the main reason children orphanage care settings are more at risk of
are placed in foster care. medical and developmental problems than
• Approximately 1 in 5 children in foster care their counterparts who have resided in foster
has been a victim of physical abuse. care.
• Foster care is intended to be a short-term • The pediatrician should closely review any
solution until a permanent placement or adop- information about the child’s medical history
tion can be made. (if available) before and after adoption.
• Family or parental leaves are recommended –– Hepatitis C serologies, if emigrating from

to provide enough time, security, and love hepatitis C-endemic area
when the adopted child arrives. –– Newborn metabolic screen for infants
• During the transition period, adoptive chil-
dren may experience withdrawal, temper tan-
trums, and sleep and feeding problems. Cultural Issues in Medical Care
Evaluation of the Immigrants • Culture can refer to race, ethnicity, national-

• Depends on the country of origin and living ity, religion, or sexual orientation.
condition, e.g., orphan or a refugee camp • A culturally competent practice provides an
atmosphere in which patients and families
Immunization Record can participate in shared decision-making.
• Immunization record from other countries • The clinician should work with individual
is acceptable as long as it contains docu- families to provide health care that is compat-
menting date, dose, and the name of the ible with the beliefs and values of the patient
vaccines. and family.
• If no immunization record or any method of
documentation is available, all the required Providing Culturally Competent Care
vaccines should be given all over. • Explain the medical condition, diagnosis, and
treatment in terms the patient and family can
Evaluation of Adopted Children understand and in their native language.
• Comprehensive physical examination, immu- • Breaking the language barrier:
nization status, and appropriate catch-up –– Use a medical interpreter in person or by
immunization other methods, e.g., by phone or video.
• Nutrition: –– Maintain eye contact with the patient or
–– Anemia family member when using in-person med-
–– Malnutrition ical interpreter.
–– Rickets • Determine if the patient and parents accept
–– Iodine deficiency the plan of care.
• Growth and development: • Provide more information and renegotiate if
–– Estimated age there is any conflict regarding the investiga-
–– Vision and hearing tions, diagnosis, or devised treatment plan.
–– Dental caries
–– Congenital defects
–– Developmental delay SPECIFIC PROBLEMS
• Investigations: AND CONDITIONS
–– Blood specimens for complete blood count
(CBC), serum lead concentration, hepatitis Gifted Child
B, human immunodeficiency virus (HIV),
and syphilis infection status; stool sent for • Children with significantly advanced skills
ova and parasites, Giardia lamblia, and and abilities in any developmental domain.
Cryptosporidium • Academically gifted children can become
–– A tuberculin skin test placed regardless of bored and rebellious in school if they lack
bacillus Calmette-Guérin vaccine status stimulating challenges.
• Giftedness should be part of the differential educational needs; advancement also effec-
diagnosis for academic failure in school. tively accelerates and shortens childhood.
• Can be associated with social and emotional • Homeschooling may impair interpersonal
effects on the child, family functioning, and experiences and socialization.
family dynamics.
Clinical Presentation ulnerable Child Syndrome (VCS)

V
• Alertness during infancy
• Early language development Background
• Advanced vocabulary • Excessive, unfounded parental concerns,
• Abstract thinking and the ability to generate anxiety, and a high frequency of health-care
original ideas use.
• Exceptional problem-solving and memory • Affected children may suffer from sleep dis-
skills orders, school problems, discipline problems,
• Early development of empathy, concern with and hypochondria.
truth and fairness in play, a mature sense of • Parent perceives a child as being at risk of ill-
humor, leadership in cooperative play, and ness or harm because of a previous threat to
perfectionism their health.
• Cognitive and academic skills often exceed-
Risk Factors
ing social, emotional, and motor skills
• Family stress, low levels of social support,
Associated Conditions low socioeconomic status, parents who rate
• Attention-deficit/hyperactivity disorder their own health as poor
• Asperger syndrome • Postpartum depression, obsessive-compul-
• Oppositional defiant disorder sive behavior, anxiety, unresolved grief over
• Learning disabilities the death of a child or family member
• Maternal history of fertility problems or
Management previous miscarriages, threatened abortion
• Provide appropriate academic or extracurric- or health concerns of the fetus, prematurity,
ular opportunities for a child with particular hyperbilirubinemia, congenital anomalies
learning abilities. • Preceding serious illness or injury to this
• Provide enrichment: child or a sibling, presence of a condition that
–– A child with particular skill and interest can is benign or resolved but considered serious
be encouraged to research the topic to the parent (e.g., functional heart murmur,
further. colic), known familial or inheritable
–– A child who has mastered the reading or conditions
mathematical concepts for her/his grade
level may be allowed to take up studies in Exacerbating Factors
logic, learn a new language, explore music • Environmental stress
or art history, or begin studying science. • Family stress
• Prevent overscheduling the child, allow time • Lack of social support
for the typical daily activities of childhood, • Low socioeconomic status
such as chores and recreation. • Poor rating of mother’s health
• Advancing them ahead in school years may not
Effect on Children
be the most appropriate approach to meet their
• Exaggerated separation anxiety
• Sleep disorders • The timing of transition to an adult health-

• Peer relationships, self-control, discipline care practitioner should be individualized for
problems each patient and not based solely on age.
• School underachievement • Encourage patients and families to identify an
• Hypochondria adult health care practitioner and involve the
• Child becoming abusive to their parents practitioner during the transition process.
• The portable medical summary and written
Management transition plan can be transferred to the new
• Early recognition and treatment. medical home to facilitate the sharing of
• Inquire regarding the sources of the parental information.
anxiety; reeducate them about their child’s
health. Management
• Inquire about the connection between past • Early discussion of future goals with the
threats and present concerns. patient, family, and other members of the
• Clarification of the child’s resolved health team to coordinate the process.
conditions and reassurance. • Promote independence and shared
• Clear and close communication with parents decision-making.
or guardians that past experiences with illness • Identification of potential obstacles to a suc-
can affect their perception of their child’s cessful transition in the domains of health
health. care, education, vocation, and independent
• When new concerns arise, a thorough history living.
and physical examination are primary. • Parents should be encouraged to acknowl-
• Extensive laboratory evaluation, radiologic edge the sexuality of their adolescent and
studies, and referral to subspecialists should young adult children as well as to foster the
be avoided unless medically indicated. development of their social independence.
• Regularly scheduled follow-up visits to dis- • The role of a surrogate decision-maker should
cuss health concerns and behavioral issues. be discussed for those with severe intellectual
disabilities or mental health conditions.
• Full independence regarding medical or other
Transition of Adolescents to Young decisions may not be appropriate.
Adulthood for Vulnerable
Populations
hronic Illness and Handicapping
C
Background Conditions
• Adolescents with chronic medical conditions
and disabilities have immense challenges General Effect of a Child with Chronic
transitioning to adult medical care. Conditions on the Family
• These could affect all domains of daily living • Parents of children with handicapping condi-
such as health care, education, vocation, and tions may exhibit grief reactions, and this
independent living. could affect the siblings.
• Increased risk of child abuse among handi-
General Considerations capped children.
• These vulnerable populations should have • Chronic conditions (e.g., ADHD, asthma, sei-
written transition plans by 14 years of age, zures, inflammatory bowel disease) may lead
which should be updated annually. to psychosocial issues.
• Use of home medical equipment (e.g., oxy- c hronically ill or handicapped child to adult
gen monitors, physical therapy, transporta- behavior, including separation from parents
tion, hygiene) may have psychosocial effects and emerging sexuality in spite of chronic
on family dynamics. illness.
Psychosocial Factors
• Disease-specific parental stress regarding a C hronic Pain Syndrome
child’s chronic medical condition is likely to
improve the management of the disorder, as • It is a constellation of syndromes that usually
long as that stress is not overwhelming. do not respond to the medical model of care.
• Excessive parental stress about their child’s • Chronic pain syndrome is a diagnosis of
chronic medical condition can impair their exclusion. Other conditions must be ruled out
ability to manage the disorder. before diagnosis.
• Chronic medical conditions in children often • Chronic pain syndrome often occurs concur-
have an overall negative impact on parental rently with irritable bowel syndrome, chronic
psychological functioning. fatigue syndrome, interstitial cystitis, chronic
headache, functional abdominal pain, or con-
Management version disorders.
• As a medical home, the pediatrician’s office • Pain is subjective, and repeated painful expe-
should coordinate specialist referrals for dis- riences can result in altered pain sensitivity
ease management. and behavioral disturbances.
• Any child with a chronic medical condition • Dealing with and tolerance to pain vary with
can qualify for a 504 educational plan a child’s developmental stage.
designed to prevent the condition from hav-
ing a significant impact on the child’s aca- Management of Chronic Pain Syndrome
demic career. • Open communication, reassurance, and
• Early intervention programs provide educa- parental presence.
tion-related services to infants and toddlers • The treatment should focus on restoration of
with a developmental delay up to 3 years of normal function (minimal disability), better
age. quality of life, reduction of use of medication,
• Individualized education plans (IEPs) address and prevention of relapse of chronic
the needs of children who qualify for special symptoms.
education by authorizing appropriate educa- • Physical and occupational therapies.
tion-related services • Exercise, desensitization, stress management,
• 504 modification plans provide education- and counseling.
related services to children with chronic or • Cognitive-behavioral therapy (CBT).
disabling conditions who do not qualify for • Rule out all organic causes.
special education.
• Supportive and nonthreatening discussion
with parents whose children have chronic
diseases. Transplantation
• Appropriate ethical decisions relating to chil-
• Growth impairment is common after all solid
dren with chronic and handicapping
organ transplants.
diseases.
• Etiologies of growth impairment may be
• A pediatrician can help the family in the
multifactorial.
facilitation of a normal progression of a
• Increased risk of neurocognitive changes and Management

education failure. • Early identification and reporting, especially
• Psychosocial stresses: waiting for future if suspected child abuse.
transplantation and the guilt of realizing that • Emergency social work or child protective
to receive a lifesaving organ, someone else services.
must die. • Parental engagement in all aspects of their
• The parents’ financial burden of time lost children’s lives is a recommended interven-
from work and fear of child’s possible tion in the treatment of aggressive youth.
organ rejection, organ loss, malignancy,
and death.
Child Abuse
Management
• Formal neurocognitive assessment of aca- Background
demic strengths and weaknesses • Neglect is the most common form of child
• Support groups for pretransplantation and abuse.
posttransplantation periods • The caregiver is the abuser of a child in 90%
• Adherence with clinic follow-up and medica- of child abuse cases.
tion regimens • Failure to thrive may be a manifestation of
abuse or neglect in children.
• Siblings of abused children are at increased
risk of abuse.
CHILD ABUSE AND NEGLECT
• Intimate-partner violence is frequently a risk
factor for child abuse.
Family and Societal Violence
• Fractures are present in a minority of physi-
Risk Factors cally abused children.
• Maternal depression. • Physical abuse is the most common cause of
• Substance use/abuse. serious intracranial injuries during the first
• Physical injuries may indicate intimate part- year after birth.
ner violence. • Shaking is a possible cause of coma in the
absence of signs of cutaneous trauma.
Possible Precipitants of Violence • Foster home placement is associated with
• Pregnancy continued risk of child abuse.
• Efforts by the partner to leave the home • Many abused and neglected children are not
• Seeking separation or divorce removed from their parents or placed in foster care.
• Moving to a shelter
Risk Factors
Effect of Violence on Children • Handicap, hyperactivity
• Exposure to stress, abuse, neglect, and vio- • Social/situational stressors (e.g., poverty, iso-
lence in growing children leads to anatomic lation, family discord, multiple births, parent-
changes and physiologic changes in the child conflicts)
brain. • Parental stress (e.g., abused as a child, depres-
• Increased risk of physical and behavioral sion, substance abuse)
problems in adults who were abused as • Abusive and neglectful parents often having
children. severely unrealistic expectations for their
child’s behavior
Clinical Presentation –– Any fracture can be the result of abuse,

• Poisonous ingestions may be manifestations especially in a nonambulatory child.
of child abuse. –– Postero-medial rib fractures near the costo-
• Bruises: vertebral junction (Fig. 27.2).
–– Keys to the diagnosis of cutaneous injury –– Classic metaphyseal lesion in infants.
include the child’s developmental stage, –– Multiple fractures at different sites and dif-
location, and pattern. ferent stages of healing.
–– Abnormal bruises will be multiple in dif- –– Spiral/oblique or metaphyseal fractures of
ferent planes and different stages of the humerus (Fig. 27.3).
healing. –– Spiral/oblique or metaphyseal fractures of
–– Patterned bruises (belt marks, whips, the femur (especially in preambulatory
straps), human bite marks, and frenulum children).
tear. –– Fractures of the scapula and sternum are
• Burns: rarely accidental.
–– A nonaccidental burn injury usually
involves the lower extremities and is
symmetric.
–– Immersion burns, when a child is forcibly
held in hot water, show a clear delineation
between the burned and healthy skin and
uniform depth.
–– They may have a stocking or glove pattern
(foot or hand held under scalding water)
(Fig. 27.1).
–– Immersion burns may have a doughnut
pattern in the buttocks (child pressed into
scalding water).
–– No splash or spill injury indicates that the
child was held in place.
• Common fractures suggestive of child
Fig. 27.2 Bone survey for suspected child abuse showing
abuse: callus formation posteriorly in ribs 5–9 on the left side
–– Abusive fractures are seen in children (arrows). Callus formation is seen also on the left seventh
younger than 18 months. more laterally (arrowhead)
Fig. 27.1 Left: Stocking

pattern burns and a distinct
line of demarcation:
waterlines. Right: Sparing
of the soles of the feet
a b • Fractures:
–– Osteogenesis imperfecta
–– Hypophosphatasia
–– Infantile cortical hyperostosis
–– Osteoid osteoma
Diagnosis
• Suggestive history and physical examination.
• The skeletal survey is mandatory in suspected
child abuse or a child with a subdural
hematoma.
• Radionuclide bone scan can reveal subtle
areas of skeletal trauma that may not be seen
on plain-film radiographic studies of bones.
Fig. 27.3 5-month-old boy brought to the emergency
• The absence of neurologic symptoms in
department with swelling and deformity of the left arm. (a)
Radiograph shows a midshaft humeral fracture. (b) Bone infants with intracranial injuries should not
survey showing metaphyseal corner fracture in the left distal exclude the need for imaging.
femur (arrow)
Management
–– Chip fracture of metaphysis is commonly • Report to a state child protective service.
due to wrenching or pulling injuries. • Team approach needed in the management of
–– Dislocated elbow, clavicular fracture, and child abuse.
toddler fracture of the tibia are infrequently • An ophthalmology consultation is needed to
indicative of physical abuse. identify retinal hemorrhages in suspected
head trauma due to shaking.
Clinical Features Commonly Mistaken for
Child Abuse Report Child Abuse
• Normal bruises occur over a bony promi- • Child abuse must be reported to a state child
nence—forehead, knees, elbows, and shins: protection agency.
–– Facial scratches on infants from their • Under state laws, physicians are legally obli-
fingernails gated to report suspected abuse or neglect as
–– Bruises that appear in the same stage of soon as possible.
healing • Physicians are protected by law from liability
• Mongolian spot, coining, cupping, and urti- when they make a report or provide informa-
caria pigmentosa. tion in good faith to CPS or law enforcement
• Accidental burn injuries usually involve the agents.
upper part of the body due to exploration and • Unsubstantiated report/finding by a child pro-
are usually asymmetric: tection agency does not necessarily mean that
–– Spill or splash injury is characterized by abuse or neglect did not occur.
irregular margins and nonuniform depth. • Failure to substantiate child abuse may be
• Contact burns will show branding type and due to failure to locate the child, failure to
mirror the object used. locate the parents, parents’ refusal to speak to
• Differential diagnosis of inflicted burns investigators, duplicate reports, child’s refusal
includes staphylococcal impetigo, herpes, to repeat history, and non-English-speaking
contact dermatitis, and toxic epidermal family.
necrolysis.
Neglect • Sexual victimization is more common among

girls than boys.
Background • Boys are less likely to disclose sexual abuse
• Neglect is the most common form of child and might be victimized more often than the
maltreatment. reported ratio.
• Teenagers have the highest rates of sexual
Types of Neglect assault.
• Medical neglect: Caregiver failed to provide • The child knows most perpetrators of sexual
adequate medical care for a child. abuse before the abuse occurs.
• Physical neglect: Caregiver was unable to • Physical disabilities, prior sexual victimiza-
provide basic needs (nutrition, shelter, tion, and absence of a protective parent are
clothes)—child abandonment. other potential risk factors.
• Educational neglect: Caregiver failed to • There is increased incidence of sexually
enroll the child in school or provide home- transmitted disease (STD) associated with
schooling, allowed frequent absenteeism, or sexual abuse.
ignored special education needs.
• Emotional neglect: Caregiver kept the child Clinical Presentation
isolated, withheld emotional support, and • An explicit description and imitation of adult
exposed the child to interpersonal violence or sexual behavior by children may indicate
substance abuse. either victimization or observation of sexual
• Supervisory neglect: Caregiver left the child acts (not fantasy).
alone or improperly supervised and failed to • Sexually abused children also can present
keep the child from safety hazards. with nonspecific physical or emotional
complaints.
Management of Child Neglect • Unexplained abdominal pain, genital pain,
• Physicians are legally obligated to report encopresis, school failure, or sleep disturbance.
cases of suspected child neglect to a child • Complaint of genital pain and genital dis-
welfare agency. charge may infrequently indicate sexual
abuse.
• When sexual abuse is suspected, the child
Sexual Abuse should be interviewed alone.
• Verbatim statements by a child may qualify
Background
as evidence in a criminal court.
• The incidence of sexual abuse cases that came
to the attention of investigators or other com- Medical History-Taking
munity professionals was 2.4/1000 US chil- • In suspected sexual abuse, the first detailed
dren under the age of 18 years. interview of a child is diagnostically critical.
• Child sexual abuse involves physical con- • It is essential to avoid repetitive interviewing
tact between the victim and the perpetrator, of an allegedly sexually abused child.
with or without oral, anal, or vaginal • Repetitive interviewing is unnecessarily
penetration. stressful and may create rote quality to
• There may not be touching; the child may be responses, increases the likelihood of leading
forced to watch sexual acts or pornography. questions, increases chance of learned
• The delay between the onset of abuse and dis- responses, and increases the chances of
closure is common. inconsistency/retraction.
• The use of anatomically correct dolls for • HIV, Chlamydia trachomatis, gonorrhea, and
interviewing has advantages in a child who is syphilis are diagnostic of sexual abuse unless
nonverbal but who can point; there may be a otherwise proven.
risk of overinterpretation.
Investigations
Examination
• Explanations to parents and the child before, Chlamydia trachomatis and Neisseria gonor-
during, and after the examination can ease rhoeae Infection
stress. • Infection may be acquired from the mother at
• Supportive, non-offending caretakers can birth.
also be comforting to the child. • Specimens from the rectum, male urethra,
• Older patients can indicate if they prefer to vagina, and urine can be tested for Chlamydia
undergo the examination with or without their trachomatis and Neisseria gonorrhoeae.
caretaker in the examination room. • Throat specimens can also be tested for
• The use of chaperones is essential during the gonorrhea.
examination of pediatric patients. • Nucleic acid amplification tests (NAATs) for
• Examination positions include supine lithot- chlamydia and gonorrhea infections in urine.
omy, supine frog-leg, and knee-chest position. • Repeat chlamydia and gonorrhea testing
• Patients who refuse should not be forced to within 2 weeks after the last contact is indi-
undergo an examination. cated in cases in which prophylactic treat-
• A normal physical examination does not ment was not given.
exclude the possibility of sexual abuse or
prior penetration. Trichomonas vaginalis
• Most sexual abuse victims have normal ano- • Wet mounts and other studies of vaginal dis-
genital examinations. charge can identify Trichomonas vaginalis
• Findings indicative of trauma include lacera- and bacterial vaginosis.
tion or bruising of the hymen, genital or peri- • Bacterial vaginosis can be unrelated to sexual
anal bruising, and hymenal transection. abuse.
• Labial adhesions, vulvar erythema, and anal
Herpes Simplex Virus
tags are not signs of abuse.
• Polymerase chain reaction testing or culture
Legal Issues of genital lesions can test for herpes simplex
• STD in a prepubertal child is presumptive virus.
evidence of sexual abuse.
Others
• Gold standard tests to diagnose sexually
• Send serologic studies for HIV, syphilis, and
transmitted infections in children should be
hepatitis B.
used.
• Laboratory testing at the time of initial pre-
• Evidence of seminal fluid is infrequently
sentation and convalescent testing for syphi-
found in sexually abused children.
lis and HIV are indicated at 6, 12, and
• Seminal fluid is unlikely to be found/persist
24 weeks post-assault.
beyond 72 h in a sexually abused child.
• Anogenital warts (condyloma acuminata) and
• Sexual abuse can recur even when families
genital herpes simplex are suspicious but not
are receiving treatment.
diagnostic of abuse.
• Pregnancy testing should be performed where • Caregiver may cause recurrent sepsis from
indicated based on the patient’s pubertal injecting fluids; chronic diarrhea from laxa-
stage. tives; false renal stones from pebbles; fever
from heated thermometer; or rashes from
Management trauma, sugar, or blood in the urine.
• Sexual abuse must be reported to a state child • Mothers have been identified as the sole per-
protection agency as soon as possible. petrators in the majority of cases.
• Treatment plans address physical health,
mental health, child safety, and psychosocial
concerns. Clues to Caregiver-Fabricated Illness
• Gonorrhea, chlamydia infection, trichomonas • The patient has bizarre symptoms.
infection, and bacterial vaginosis: • History, physical examination findings, and
–– Prophylactic antibiotics for patients who appearance of health are inconsistent.
present within 72 h of an assault. • The caregiver is not satisfied with normal or
–– These prophylactic antibiotics are gener- reassuring test results.
ally not prescribed for prepubertal patients • A sibling of the patient has an unexplained
because the incidence of sexually transmit- illness.
ted infection is low. • The caregiver uses social media to solicit
–– There is a low risk of spread to the upper donations based on the child’s illness.
genital tract. • The caregiver has a history of somatization
• HIV postexposure prophylaxis: disorder.
–– A 28-day course of a 2- to 3-drug regimen • Parents and children with this condition may
initiated as soon as possible within 72 h of exhibit significant ongoing psychological
potential exposure and careful follow-up problems.
• Pregnancy prevention:
–– Emergency contraception should be offered Management
when female pubertal patients present • Requires a multidisciplinary child protection
within 72 h till 120 h. team that includes the state social service
• Mental health issues need to be addressed; agencies.
urgent psychiatric referral if there are suicidal • Consult child protection agents, communi-
ideations. cate with the patient’s specialists, and/or sub-
• It is very important not to assign blame to the mit a detailed report to the state child welfare
victim in helping families cope with sexual agency upon suspecting the diagnosis rather
abuse. than waiting until the evaluation or unneces-
sary treatment is complete.
• Family therapy to address ongoing family
Caregiver-Fabricated Illness issues.
(Munchausen Syndrome by Proxy)
• Caregiver falsely claims that the child has a PEARLS AND PITFALLS
physical or psychological signs or symptoms
of illness or causes injury or disease in the • Expression of grief is determined by chrono-
child with the intention of deceiving others. logical age and level of cognitive
• Caregiver-fabricated illness may result in development.
harm to the child through unnecessary proce- • Divorce and/or separation has long-term dev-
dures and treatments. astating effects on all aspects of the life of the
child and family.
pain in the neonate: an update. Pediatrics.

• Adolescents with chronic medical conditions
2006;118:2231–41.
and disabilities should have written transition
Asnes AG, Leventhal JM. Managing child abuse:
plans by 14 years of age, which should be
updated annually. general principles. Pediatr Rev. 2010;31:
47–55.
• Children exposed to high-conflict parental
Bhargava S. Diagnosis and management of com-
interactions may have difficulty forming
meaningful relationships. mon sleep problems in children. Pediatr Rev.
2011;32(3):91–9.
• During adoption, the pediatrician should help
Brown P, Tierney C. Munchausen syndrome by
review any information about the child’s
proxy. Pediatr Rev. 2009;30:414–5.
medical history (if available) before and after
adoption. Dubowitz H, Feigelman S, Lane W, Kim J. Pediatric
primary care to help prevent child maltreatment:
• Limit screen time (TV, internet, etc.) to 2 h/
day. the Safe Environment for Every Kid (SEEK)
model. Pediatrics. 2009;123:858–64.
• Foster care is intended to be a short-term
Flaherty EG, Sege RD, Griffith J, et al. From sus-
solution until a permanent placement or adop-
tion can be made. picion of physical child abuse to reporting: pri-
mary care clinician decision-making. Pediatrics.
• Encopresis occurs with an 80% male pre-
dominance and often a positive family 2008;122:611–9.
history. Fortin K, Jenny C. Sexual abuse. Pediatr Rev.
2012;33:19–32.
• Somatization disorders occur in children who
are genetically predisposed. Gold LM, Kirkpatrick BS, Fricker FJ, Zitelli
BJ. Psychosocial issues in pediatric organ trans-
• Chronic pain syndromes are diagnoses of
plantation: the parents’ perspective. Pediatrics.
exclusion. Other conditions must be ruled out
before diagnosis. 1986;77:738–44.
Holsti L, Grunau RE. Considerations for using
• Sibling rivalry and jealousy are common.
sucrose to reduce procedural pain in preterm
• Anxiety disorders have a genetic predisposi-
tion and environmental factors. infants. Pediatrics. 2010;125:1042–7.
Pagel JF. Nightmares and disorders of dreaming.
• Night waking may be associated with separa-
tion anxiety. Am Fam Physician. 2000;61:2037–42, 2044.
Pipan M, Blum N. Basics of child behavior and
• Organ transplantation can have psychosocial
and financial stresses on the family. primary care management of common behav-
ioral problems. In: Voight RG, Macias MM,
• Under state laws, physicians are legally obli-
Myers SM, editors. Developmental and behav-
gated to report any suspected abuse and
neglect. ioral pediatrics. Elk Grove Village: Pediatrics;
2011. p. 49–50.
• Neglect is the most common form of child
maltreatment. Zeltzer LK, Krane EJ. Pediatric pain manage-
ment. In: Kliegman RM, Stanton BF, St. Geme
• STD in a prepubertal child is presumptive
evidence of sexual abuse. III JW, Schor NF, Behrman RE, editors. Nelson
textbook of pediatrics. 19th ed. Philadelphia:
Saunders Elsevier; 2011. p. 360–75.
Zuckerman B. Nightmares and night terrors. In:
Suggested Reading Parker S, Zuckerman B, Augustyn M, editors.
American Academy of Pediatrics, Committee Developmental and behavioral pediatrics: a
on Fetus and Newborn; Fetus and Newborn handbook for primary care. 2nd ed. Philadelphia:
Committee. Prevention and management of Lippincott Williams & Wilkins; 2005. p. 251–2.
Ethics
28
Marwa Abdou
GENERAL –– Circumcision performed on a newborn by a

pediatrician other than the physician the
Negligence and Malpractice mother consented to perform the procedure
• Pediatricians are expected to adhere to the

highest level of professional conduct ood Samaritan Laws
G
• If their behavior is found to be substandard
and a patient is harmed as a result, the pedia- • Laws that protect pediatricians and caregivers
trician can be sued for malpractice from prosecution for medical mistakes, as
• Pediatricians are sued most commonly for long as the caregivers are acting voluntarily
errors in diagnosis related to several condi-
tions, e.g.,
–– Meningitis ETHICAL PRINCIPLES
–– Pneumonia
–– Appendicitis Autonomy
–– Asthma
• It is the patient’s right to make decisions and
–– Developmental dysplasia of the hip
act on them freely and without interference
• The physician must understand the risks, ben-
efits, and alternatives of any proposed therapy
Battery
or procedure in order to help the patient or
• Performing a procedure or providing treat- guardian of the child make a decision that is
ment without informed consent consistent with his or her values
• Treatment that is substantially different from • Example: If a patient refuses a specific treat-
that to which the patient consented is consid- ment or procedure, it is the physician’s obli-
ered battery even with the best intentions gation to respect that autonomy and not
• Unauthorized substitution of one doctor for forcefully override the refusal
another comes within the definition of bat-
tery, especially when it involves invasive pro-
cedures, e.g., Beneficence
• The primary ethical principle in pediatrics
M. Abdou (*) • Beneficence is doing good for others and act-
Department of Pediatrics, Texas Tech University Health Science ing in the patient’s best interest. This includes
Center, El Paso, TX, USA
e-mail: marwaali@doctor.com the consideration of treatment efficacy and

904 M. Abdou
the potential to lessen disability or MEDICAL DECISION-MAKING

complications
• Example: Referring a child to an expert in P arental Authority
the field in order to provide the best treatment
available Parents’ rights
• Parents have the right to make decisions for
their children
Nonmaleficence • Affection and close family ties make parents
the most suitable party to reach the best deci-
• The principle of do no harm sion for their children
• Example: Not ordering a head computed • Parents will carry the consequences of any
tomography (CT) scan to a well-appearing decision made
child with a minor head laceration
Limitations
• Parents have no right to refuse life-saving
Veracity treatment for a child
• Pediatricians may seek help from a hospital
• The principle of telling the truth
ethics committee or the court if time allows,
• Example: Informing an adolescent regarding
e.g., parents refusing critical treatment or an
their diagnosis
operation that is not immediately
life-threatening
Fidelity
• The quality of being faithful and maintaining M
edical Decisions in Complex
confidentiality Conditions
• Example: Maintaining the privacy of an
emancipated minor with a sexually transmit- Supportive team in making difficult decisions
ted disease (STD) • Psychosocial interdisciplinary team
• Pediatric palliative care team
• Social worker
Confidentiality • Case manager
• Child life specialist
• Not to divulge a patient’s personal informa- • Chaplain
tion without his or her permission • Psychologist
• Bereavement specialist
• Palliative care physician
Justice
Description of Team Functions
• The principle of being fair • Social workers: Quickly link families to
• The ideal distribution of risks and benefits; government-sponsored insurance programs,
prudently legislating potential conflict financial support; help resolve custody or
• Example: Clinical research trials in children guardianship issues
28 Ethics 905
• Case managers: Work closely with social • Pediatricians must provide parents or guard-
workers and other clinicians to help coordi- ians with relevant risks and benefits of the
nate outpatient appointments, tests, and available options and provide specific
treatments recommendations
• Child life specialists: Able to explain the cur- • Pediatricians should not offer a list of vague
rent situation and upcoming procedures in choices
terms that the child can understand
• Chaplains: Care for the spiritual needs of the End-of-life planning
patient and family • A multidisciplinary team approach to inform
• Psychologists: Trained to listen to and help the family and provide more time for them to
with the spoken and unspoken concerns of decide in the best interest of the child
the family and/or patient • The discussion about end-of-life care should
• Bereavement specialists: Build rapport and take place early in the course of a chronic
help the patient and family deal with antici- disease
patory grief regarding the diminishment of • Withdrawal of life-sustaining medical thera-
the child’s expected lifespan or the very pies should occur with agreement from those
real possibility of the child’s actual death accountable after they have been allowed
• Palliative care physicians: Can begin therapy adequate time to make a fully informed
while awaiting a referral to the appropriate decision
sub-specialist
• Example: A child with respiratory distress
who is dying: CONSENTS
–– It is ethically acceptable to treat symptoms
of respiratory distress in a dying patient Informed Consent
even if it may hasten death because of the
“doctrine of double effect” • Approval of the legal guardian of the child
–– Narcotics and benzodiazepines at standard and/or of the competent child for medical
doses are effective medications to treat the interventions following appropriate and clear
discomfort of respiratory distress in dying information
patients
–– The medication has 2 effects: Elements of informed consent
◦◦ Positive (treating symptoms) • Provision of information about the nature of
◦◦ Negative (hastening death) the illness or condition; proposed diagnos-
–– The intent of the positive effect can be tic steps and/or treatments; the probability
honored of their success, the potential risks, and
benefits make up the elements of informed
General rules consent
• Pediatricians are not obligated to provide • Information about the uncertainties of the
futile care, which includes prolonged or inva- proposed treatment and alternative treat-
sive therapies on patients who are not likely ments, including the option of no treatment or
to derive benefit from them comfort measures only
906 M. Abdou
• Assessment of patient and surrogate under- in a way that they can understand and to give
standing and medical decision-making capac- their assent
ity should be made • This consent/assent process must promote
• Ensure that there is a voluntary agreement and protect the dignity, privacy, and confiden-
with the plan tiality of the child and his or her family
• Consent or assent is required for all aspects of
medical care—for preventive, diagnostic, or
Assent by Pediatric Patients therapeutic measures, and for research
Informed assent
• A child's agreement to medical procedures in R efusal of Treatment or Procedure
circumstances where he or she is not legally by a Child
authorized or lacks enough understanding for
giving consent competently • A child may refuse a treatment or procedure
• Doctors should carefully listen to the opinion that is not necessary to save life or prevent
and wishes of children who are not able to serious harm
give full consent and should strive to obtain • Children should generally be allowed to par-
their assent ticipate in their own medical decision-making
• Assent from children even as young as 7 years when possible
can foster the moral growth and development • Mature and emancipated minors may be able
of autonomy in young patients to make their own decisions
Benefits of informed assent

• Helps the patient to achieve a developmen- efusal of Treatment or Procedure
R
tally appropriate awareness of the nature of by Parents or Guardians
his or her condition
• Tells the patient what he or she can expect Possible causes of disagreement
with tests and treatments • Different religious beliefs
• Makes a clinical assessment of the patient’s • Moral values
understanding of the situation and the factors • Believing that the treatment is not necessary
influencing how he or she is responding or preferring other alternatives that may not
• Solicits an expression of the patient’s willing- be the best for the child
ness to accept the proposed care
• Children and adolescents have a right to give Appropriate action in cases of disagreement
their opinion on medical decision-making in • The best initial step, in general, is to try to
clinical practice and research understand why the parents are refusing the
treatment or the procedure and try to convince
them
Principles in Medical • If the treatment is necessary to save life or
Decision-Making prevent serious harm, e.g., refusing antibiotic
treatment for meningitis, blood transfusions
• Pediatricians have the responsibility to deter- in cases of life-threatening anemia, or chemo-
mine the ability and competence of the child therapy that offers a good chance of cure in
for giving his or her consent or assent an otherwise universally fatal cancer:
• All children, even those not judged as compe- –– Proceed with the treatment or procedure
tent, have a right to receive information given without informed consent
28 Ethics 907
–– The pediatrician has the duty to act in the • Pediatricians should protect adolescent confi-
best interest of the child dentiality unless there is abuse or serious risk
• If not life-threatening or there is no immedi- of harm
ate harm, but the risks and complications are
evident without treatment: Examples:
–– Consult the institutional ethics committee Parents requesting drug testing of their adoles-
or refer to the court cent without his or her knowledge (surrepti-
–– May call the state child protection agencies tious drug testing) → The best approach:
for medical negligence • Building a trusting relationship with the
–– May terminate the physician-patient-par- adolescent and parents is the best next step
ent relationship • Interview the adolescent alone; the conversa-
• Low risk or no imminent danger to the child, tion may lead to a discussion about drugs and
e.g., refusing hepatitis B, or vitamin K in the other potentially risky activities
hospital after birth: • Do not test the child without his or her knowl-
–– Explore the reason why parents are refus- edge, as that will inevitably seriously impair
ing the vaccine or vitamin K the physician-patient relationship
–– Explain why physicians strongly recom- • Try to convince the parents that this is the
mend vitamin K or hepatitis B vaccinations best approach, because even if the child is
for all newborns indeed a drug addict, he or she may resist
–– Inform the parents of the medical indica- intervention efforts
tions and the risks, and the pediatrician
should try to convince the parents to con- Adolescent requesting birth control pills → The
sent, e.g., the hemorrhagic disease in the best approach:
newborn is a life-threatening illness that is • Maintain confidentiality and trust
easily preventable by giving vitamin K; • Oral contraceptives are much safer for ado-
should the disease process begin, it is dif- lescents than is pregnancy
ficult to treat • An adolescent who seeks contraception is
–– May ask the parents to sign a declination acting responsibly and maturely, and this is
form, indicating that the vitamin K or hep- an opportunity for an open conversation
atitis B has been recommended and the • Ask if she has a boyfriend? What is his age?
risks have been explained If he is much older, there may be a possibility
• Parents may refuse non-emergent treatment that this is an abusive relationship
or procedures, e.g., treatment of acne, sutur- • Report abusive relationships to appropriate
ing lacerations, etc. authorities. The age of consent may differ
from state to state
• Convince the adolescent to inform her par-
Adolescent Consent in Special ents or another trusted adult
Situations • Inform the adolescent that her parents may
know about the prescription if she is under
• Adolescents have the right to consent to the their insurance health plan
investigation and treatment of sexually trans- • Counsel about the risk of sexually transmitted
mitted diseases, contraceptive services, and diseases
prenatal care
• Adolescents can access mental health and A 16-year-old female who is the mother of a
substance abuse prevention and treatment 2-month-old infant and who requires surgery to
services remove her gallbladder
908 M. Abdou
• She can provide informed consent for herself • Pediatricians should be very cautious about
(emancipated minor) ordering predictive genetic testing for minors
without parental consent, as this testing can
Emancipated minors can give informed consent have serious psychological, social, and medi-
for medical care if: cal ramifications for the minor and other fam-
• He/she is married ily members
• In the military • The anticipated outcomes of a condition can
• A parent change based on the social support, health-
• Self-supporting while not living with parents care, and services available to individuals
• A high school graduate with different conditions, e.g.,
––
Positive cases of Huntington’s disease,
which usually manifest during adulthood
ETHICS IN GENETICS
se of Technology for Genetic
U THICS IN COCHLEAR
E
Studies in Genetic Counseling IMPLANTS
• Families can find out earlier about possible Background (see Chap. 18 Ear, Nose, and Throat
genetic variations that could affect their chil- (ENT) for more information)
dren by using genetic testing for example: • Traditional methods used for deaf education
–– Whole exome sequencing include: American Sign Language, which is
––
Maternal noninvasive prenatal screening very successful if started early in life, and oral-
(NIPS)/cell free placental DNA testing ism, which is speechreading with some limita-
tions as some words have same lip movements
Duties of pediatricians
• Providing accurate, up-to-date, and balanced Variable outcome
information following a prenatal or postnatal • Some children who receive implants are able
diagnosis of a genetic condition will help in a to function well in the hearing world
smooth and positive transition • Others continue to require special assistance
• Not to focus exclusively on the genomic out- or to use sign language along with spoken
comes and medical issues to avoid the risk of language
leaving parents feeling anxious and
frightened Duty of pediatricians
• Even with a full spectrum of information, • Pediatricians need to understand the options
patients are still likely to undergo an adjust- and be prepared to help parents sort through
ment process and some degree of grief the complex data and multiple options to
arrive at a decision that is best for themselves
and their children
Predictive Genetic Testing
• Predictive genetic testing of children for IMPERILED NEWBORN INFANTS
adult-onset genetic disorders is not recom-
mended until the child reaches adulthood or Newborns between 23 and 24 weeks of
adolescence. If the child has a mature deci- gestation
sion-making capacity, genetic counseling can • Such neonates are at a high rate of mortality
be considered, with informed consent and high risk of diminished quality of life
28 Ethics 909
• Ongoing discussions about care at the time of Action when a child is declared dead
birth should be made jointly with the family • If consent for organ donation is declined by
before delivery the family, breathing and circulatory support
• Parental wishes regarding resuscitation should should be discontinued
be respected • No recommendation or consent is required
Viability
• Viability is a reasonable chance of survival ORGAN DONATION/
with advanced medical support TRANSPLANTATION
• No uniform agreement exists as to the exact
timing of fetal viability Time of approach
• The family should not be approached by any-
Non-initiation of resuscitation may be appro-
one about organ donation before the declara-
priate in the following cases:
tion of death
• Confirmed gestation less than 23 weeks
• Birth weight less than 400 g Appropriate steps in approaching the family
• Anencephaly about organ donation
• Confirmed lethal genetic disorder or • Confirmation and declaration of death
malformation • Obtaining consent from the family for organ
recovery
• Inform local organ procurement organization
DEATH AND DYING CHILDREN (OPO)
• The family should be approached by the OPO
Death representative regarding organ donation
• Irreversible cessation of circulatory or respi-
ratory functions or irreversible cessation of
all functions of the entire brain, including the RESEARCH INVOLVING
brainstem
CHILDREN
Determination of death by either of the follow-
ing criteria Critical Criteria Required to Conduct
• Neurologic a Clinical or Drug Trial in Children
• Circulatory
• Consent of guardians and the child (7 years
Brain death declaration requires that the fol- and older)
lowing examinations be done twice • The informed consent should be written in a
• Physical examination language that can be easily understood, at a
• Apnea testing sixth to eighth grade reading level for adult
participants
Death is declared after the second examination • Trial design appropriate to the research
confirms brain death question
• Cerebral blood flow scanning and electroen- –– Targeted to help understand, prevent, or
cephalography should be performed only if alleviate a serious condition that specifi-
any component of the physical examination cally affects the pediatric population
or apnea testing cannot be performed (for –– Congruent with all local, regional, and
more details, see Chap. 8 Critical Care) national regulatory guidelines and laws
910 M. Abdou
–– Meaningful and measurable outcomes • Religious beliefs of the family must be

–– Adequate comparative data and adequate respected
enrollment numbers • Parents must be held accountable for with-
–– Conducted in the best interest of the child holding medical care when doing so would
–– Minimize harm or a minor increase over likely result in death or suffering
minimal risk
–– Scientifically applicable Examples:
–– Independent data and safety monitoring
committee (DSMC) for all phase 3 drug Fish Oil
trials • May improve the symptoms of attention-defi-
cit/hyperactivity disorder (ADHD) in some
Financial incentives children
• Healthcare providers are prohibited to receive • Minimal adverse effects
financial incentives for recruiting children to
Melatonin
participate in clinical drug research
• Used for functional sleep disorders to
Parents and minor rights decrease sleep latency
• Retain the right to withdraw consent/assent • Long-term studies on the safety and efficacy
and participation in the study at any time dur- of pediatric use are lacking
ing the process
Probiotics
• Used for treatment of acute infectious diar-
rhea; however, Lactobacillus rhamnosus is
COMPLEMENTARY not effective for the treatment of acute gastro-
AND ALTERNATIVE MEDICINE enteritis in young children
(CAM) • May decrease functional abdominal pain
symptoms in some children
Classification • Used in the prevention of atopic dermatitis in
• Natural products, e.g., botanicals, vitamins predisposed children, however, probiotics not
and minerals, and probiotics effective for atopic dermatitis
• Mind and body practices, e.g., acupuncture, • Used in preventing necrotizing enterocolitis
relaxation techniques and late-onset sepsis in preterm infants
Ethical considerations Manipulative, movement, and body-based

• Seek reliable, evidence-based information practices
about the safety and effectiveness of specific • For example, osteopathic manipulation, chi-
therapies and therapists ropractic adjustments, and massage
• Identify risks or potential harmful effects • Serious complications are possible with chi-
• If therapy is both safe and effective→ recom- ropractic treatment of children; however,
mend the therapy such adverse effects are rare and related to
• If the therapy is not safe and is not effective high-velocity, extension, and rotational spinal
→ discourage its use manipulation
• If the therapy is not safe but is effective → • It is critical to exclude abnormal anatomic
monitor closely or discourage its use or neurologic findings before any manual or
• Nonjudgmental approach to the use of CAM manipulative therapy is used on a child or
can prevent harm resulting from interactions adolescent
with traditional medical therapy
28 Ethics 911
Acupuncture • Conflicts of interest can occur in research,

• Acupuncture is performed using solid-core, education, and clinical practice
small-gauge sterile needles to penetrate the
skin Examples of financial conflict of interest
• Used in the treatment of pediatric headache • Accepting gifts from pharmaceutical
and migraine and treatment of postoperative companies
pain • Receiving outside funding for educational
• Acupuncture is generally safe in the pediatric programs
population when practiced by an appropri- • Having relationships with pharmaceutical
ately trained practitioner companies
Spirituality Disclosure of any potential conflicts of interest

• Spiritual healing includes prayer is an essential step in mitigating them
• The belief that praying for someone else can
help cure their illness
• Mind-body therapies may delay the diagnosis PEARLS AND PITFALLS
or treatment of serious illness
• Performing a procedure or providing treat-
ment without informed consent is considered
MEDICAL TESTIMONY a battery even with good intention.
• The 4 principles of medical ethics are respect
• It is ethical for pediatrician to testify as an for autonomy, beneficence, nonmaleficence,
expert witness and justice.
• Recommendation according to the American • Clinicians should make every effort to work
Academy of Pediatrics: Physicians should with families to find mutually acceptable deci-
contribute as medical experts only to cases in sions for the medical care of their children.
which they possess true expertise and related • When parents refuse a proposed treatment
experience procedure, the best initial step is to engage
them in dialogue to try to understand why they
Pediatricians responsibilities are rejecting it and to try to convince them of
• Ensure that their testimony is: its efficacy.
–– Complete, accurate, and unbiased • In complicated cases, multidisciplinary meet-
–– Based on a complete understanding of cur- ing with all involved specialists might help.
rent medical evidence and standard of care • When disagreements persist between families
• Transcripts of courtroom testimony in medi- and the medical team, consultation with the
cal malpractice cases may be submitted for institutional ethics committee may be helpful.
peer review • If the CAM is not safe and is not effective,
discourage its use.
CONFLICT OF INTEREST
Suggested Reading
Definition American Academy of Pediatrics Committee on
• Any situation that creates a risk that profes- Fetus and Newborn, Bell EF. Noninitiation or
sional judgment or actions regarding a pri- withdrawal of intensive care for high-risk new-
mary interest will be excessively influenced borns. Pediatrics. 2007;119:401–3.
by a secondary interest
912 M. Abdou
Committee on Pediatric Research. Policy state- Nakagawa TA, Ashwal S, Mathur M, Mysore MR,
ment: promoting education, mentorship, and Bruce D, Conway EE Jr, Society of Critical
support for pediatric research. Pediatrics. Care Medicine; Section on Critical Care
2014;133:943–9. and Section on Neurology of the American
De Lourdes Levy M, Larcher V, Kurz R, Ethics Academy of Pediatrics; Child Neurology
Working Group of the Confederation of European Society, et al. Guidelines for the determina-
Specialists in Paediatrics (CESP). Informed tion of brain death in infants and children: an
consent/assent in children. Statement of the update of the 1987 task force recommendations.
Ethics Working Group of the Confederation of Pediatrics. 2011;128:e720–40. Crit Care Med.
European Specialists in Paediatrics (CESP). Eur 2011;39:2139–55.
J Pediatr. 2003;162:629–33. Opel DJ, Olson ME. Bioethics education and
Fanaroff JM. Medical malpractice/expert tes- resources. Pediatr Rev. 2012;33:370–3.
timony/disclosure of errors. Pediatr Rev. Opel DJ, Feemster KA, Omer SB, Orenstein
2010;31:e24–7. WA, Richter M, Lantos JD. A 6-month-old
Karkazis K, Rossi WC. Ethics for the pediatrician: with vaccine-hesitant parents. Pediatrics.
disorders of sex development: optimizing care. 2014;133:526–30.
Pediatr Rev. 2010;31:e82–5. Saul RA, Meredith SH. Beyond the genetic diag-
Lantos J. The patient-parent-pediatrician relation- nosis: providing parents what they want to
ship: everyday ethics in the office. Pediatr Rev. know. Pediatr Rev. 2016;37:269–78.
2015;36(1):22–9; quiz 30.
Research and Statistics
29
BIAS AND STUDY DESIGN 4. Pygmalion effect bias—Occurs when the

researcher’s belief in a specific treatment
Bias modality efficacy changes the outcome of the
treatment
• Bias is the result of differences between the 5. Hawthorne effect—Occurs when the sub-
study groups jects of the research study change their own
• Bias is a systematic error in the study design behavior. Example: Some people in the
that can decrease the ability to find a relation- “smoking group” stop smoking during the
ship between the exposure and the outcome study
of interest 6. Procedure bias—Occurs when research sub-
• Bias should be minimized in the study design jects are not treated equally
• Some forms of bias can attempt to be
accounted for in statistical analysis How to reduce bias:
1. Randomization—Subjects should be ran-

Common types of bias domly selected
1. Confounding bias—Occurs when an associ- 2. The use of a double-blind study so that nei-
ation between an exposure and an outcome is ther researchers nor test subjects can identify
distorted by another variable. Example: the true treatment, e.g., neither party has any
Smoking → Lung cancer. However, certain idea as to who is receiving the active drug and
members of the study group were exposed to who is receiving the sugar pill (placebo)
environmental toxins, so the environmental 3
. Maximize follow-up so that the number of
toxins would be a confounding variable subjects who are lost is kept to a minimum
2. Selection bias—Occurs when the subjects 4
. Researchers should try to minimize their own
selected truly do not represent the intended prejudices and opinions about a particular
population to be studied, i.e., nonrandomiza- treatment
tion of the study group 5. Use of a standardized protocol that is applied
3. Recall bias—Occurs when research subjects to all subjects of the research study
inaccurately recall previous exposures or
events. Example: A parent with a child who
has cancer may link certain exposures to the Study Designs
cancer
Randomized controlled trials
S. O. Kukoyi-Maiyegun (*) • Best study design to evaluate the risks and
benefits of a proposed new treatment
e-mail: sitratullah.maiyegun@ttuhsc.edu

• Establishes causal relationships between • Causation cannot be determined from cross-

treatments and outcomes sectional prevalence studies
• Optimal way to evaluate the effect of 2 differ- • Can study multiple outcomes and exposures
ent treatments for a disease • Cannot infer causality
• Has high internal validity • Risk of confounding variables
• Reduced risk of confounding variable • Less useful for rare exposures or outcomes
• Reduced external validity
• Expensive, time-consuming variables Case studies
• Useful for rare outcomes
Cohort studies • Convenient and inexpensive
• A population-based cohort study is best for • Lack of a comparison group
obtaining valid information about the prog- • Cannot infer causality
nosis of a condition over time • Risk of confounding variables
• A prospective study that stratifies subjects
into groups based on the presence or absence Case series
of a proposed risk factor and then follows the • Descriptive study design that is inexpensive
subjects prospectively for outcome and convenient but with limited uses
• Can reveal important details about the natural • Best used for generation of etiologic hypoth-
history of the condition being studied eses, health planning purposes, and allocation
• Useful for sequential events of resources
• Can study multiple outcomes from
exposures Systematic reviews
• Requires large sample size • A comprehensive review of the literature on a
• Risk of confounding variables clinical question
• Difficult to study rare outcomes • Includes a descriptive results section summa-
• Prospective: expensive rizing the findings and addressing the quali-
ties of the included studies
Case-control studies
• Useful to study individuals with a disease Meta-analysis
compared to individuals without the disease • Uses statistical methods to combine the
to evaluate risk factors and outcomes for the results of multiple studies on a given topic
disease • Compilation of evidence that potentially has
• Case-control study groups are defined by the greater power to inform clinical decisions
outcome and exposures ascertained than would an individual study in the system-
retrospectively atic review or meta-analysis
• Useful for rare outcomes • If the quality of the studies included in the
• Can study several exposures systematic review or meta-analysis is poor,
• Inexpensive the summary conclusions are similarly
• Risk of confounding variables inadequate
Cross-sectional studies Case reports

• Best method to ascertain the efficacy of a • Aid in recognizing and describing new dis-
diagnostic test by comparing a new diagnos- ease processes or rare manifestations
tic or screening test with a known gold stan- • Describe the disease in the context of comor-
dard test in the same population group bidities and individual characteristics
• Identify drug adverse effects
29 Research and Statistics 915
• Help to illustrate the diagnostic process and EPIDEMIOLOGICAL RESEARCH

help students apply the literature to an indi-
vidual patient
METHODS
• Help identify emerging health conditions
Prevalence vs. Incidence
• Show how exposures and disease outcomes
are related Both provide important information that leads to
• Can stimulate important research questions the prioritization of public health issues, develop-
and help guide hypotheses ment of public health initiatives, and the develop-
• Are purely descriptive and one of the weakest ment of future studies
forms of evidence
• Cannot be used to make inferences about the Prevalence
broader population • The percent of a group of people with a spe-
• Cannot prove causality cific condition in the population being studied
• Prevalence is the total number of existing cases
Anecdotal evidence
of a disease/total population being studied
• Clinician’s personal experience
• Shares some characteristics with case reports Incidence
• Lacks the strength of data collected via rigor- • The total number of new cases within a spe-
ous methodology that also involves signifi- cific period of time
cant numbers • Number of new cases in a specific time
• Can suggest hypotheses and lead to the cre- period/total population at risk during that
ation of credible studies same time period
Descriptive epidemiologic studies Prevalence vs. incidence
• Follow-up on case reports • Prevalence will be greater than incidence in
• Used to describe patterns of disease in the chronic conditions
population according to person, place, and • Prevalence and incidence will about the same
time in acute conditions
• Do not test a predefined hypothesis or deter-
mine a cause-and-effect relationship
• Used to develop hypotheses for subsequent Screening and Diagnostic Testing:
analytic studies Four Square Model (Fig. 29.1)
• Use a variety of tools, including surveillance
reports, cross-sectional analyses, and surveys False positive
• A false positive (FP) occurs when the test
Statistically significant vs. clinically significant reports a positive result for a person who is
studies disease-free
• In both studies, results are unlikely to be the
result of chance
• Statistical significance does not imply clini- TP FP #WHO TEST POS
cal significance
• Clinically significant results should be gener-
alizable and reproducible FN TN #WHO TEST NEG
• Clinically significant study results should
have an effect that suggests an alteration in
Fig. 29.1 Foursquare. TP true positive, FP false positive,
practice or decision making FN false negative, TN true negative
False negative ositive Predictive Value (PPV)

P
• A false negative (FN) occurs when the test
reports a negative result for a person who • Probability of correctly identifying those who
actually has the disease truly have the disease among those whose
tests are positive
Sensitivity: Screening • Likelihood that a patient with a positive test
• Probability of correctly identifying those who has the condition
truly have the disease • PPV = TP/(TP + FP)
• True positives (TP)/patients with the disease • Predictive values are dependent on the preva-
• TP/(TP + FN) (see Fig. 29.1) lence of the disease
• A highly sensitive test helps rule out disease • The higher the prevalence of a disease, the
because the higher the sensitivity, the lower higher the PPV of the test
the number of false negatives
Specificity: Confirmation egative Predictive Value (NPV)

N
• Probability of correctly identifying those who
do not have the disease • Probability of correctly identifying those not
• True negatives/patients who do not have having the disease given a negative test
disease • Likelihood that a patient with a negative test
• TN/(FP + TN) that truly does not have the disease
• A highly specific test is used to confirm dis- • TN/(FN + TN)
ease after a screening test and “rules in” dis-
ease because the higher the specificity, the
lower the number of false positives. Likelihood Ratio (LR)
Useful mnemonics • Probability that an individual with disease
• SPIN—SPecific tests rule IN the condition has a positive test result divided by the prob-
when they’re positive ability that an individual without disease has
• SNOUT—SeNsitive tests rule OUT the con- a positive test result
dition when they’re negative • The degree to which the results of the test
change the probability
Summary • The LR combines the sensitivity and specific-
• A good screening test is a rapid, inexpensive ity of the test into a single measure
assay and has a good sensitivity (i.e., a nega- • The LR for a positive test can be calculated
tive test is reliable) from the sensitivity and specificity as follows:
• A positive or equivocal test should generally Sensitivity/(1- specificity), when sensitivity
be confirmed with a more specific confirma- and specificity are expressed as decimals.
tory assay • Post test probability can be determined by
• Example: HIV screening is done with using the Fagan nomogram.
enzyme-linked immunosorbent assay • Fagan nomogram:
(ELISA) and then confirmed with a western
blot (protein immunoblot)
–– A tool that allows the determination of post- • Internal consistency reliability is a measure
test probability given the pretest probability of the consistency of the items within a test
of disease and the LR for the diagnostic test • Interrater reliability is the degree to which 2
–– The pretest probability of disease can be raters independently score an observation
estimated based on disease prevalence similarly
Sample size
DESCRIPTIVE STATISTICS • Increasing sample size improves the ability to
detect adverse events
alidity (Accuracy) vs. Reliability
V • For studies in which the difference in mea-
(Precision) sured effect is small, a larger sample size is
required to detect a statistically significant
Validity (accuracy) difference
• Addresses whether an instrument or test actu- • Power is the statistical probability that a study
ally measures what it is intended to measure will not mistakenly accept a null hypothesis
• Validity assesses how accurate and how true and conclude that there was no effect when
the test measurements are there actually was one
• Criterion validity is the degree to which the • Having a larger sample size increases the
measurement correlates with an external cri- power of the study
terion or another instrument or test that is • A larger sample size reduces the likelihood of
considered valid making a type I or type II error
–– Convergent validity is the degree to which
independent measures of the same con-
struct are highly correlated dds Ratio and Risk Types
O
–– Predictive validity is the ability of an (Table 29.1)
instrument or test to predict some future
criterion Odds ratio
–– Discriminant validity requires that an • Defined as the odds of having a disease in the
instrument or test shows little or no corre- exposed group divided by the odds of having
lation with measures from which it differs the disease in the unexposed group
• Content validity refers to the extent to which • Odds ratio calculates the relative risk (RR) if
aspects of items that make up an instrument the prevalence of the disease is low. It can be
or test are representative of a particular calculated for case-control study (retrospec-
construct tive study)
–– Face validity is a judgment about whether
Odds ratio formula = A × D/B × C
elements of an instrument make intuitive
Interpretation
sense
• OR > 1—Exposure is associated with a
–– Sampling validity refers to whether the
higher odds of an outcome
instrument incorporates all of the aspects
under study
Table 29.1 Calculating the odds ratio
Reliability (Precision)
Disease present Disease absent
• The consistency or repeatability of scores (+) (−)
• Test–retest reliability assesses whether an Risk factor/exposure A B
instrument or test yields the same results each (+)
time it is used with the same study sample Risk factor/exposure C D
under the same study conditions (−)
• OR < 1—Exposure is associated with a lower • Example: Does exercise reduce cholesterol

odds of an outcome levels?
• OR = 1—No effect of the exposure on an • Null hypothesis: Exercising daily has no
outcome effect on cholesterol levels
• Example: Exposure = cigarette smoke. Alternative hypothesis

Outcome: lung cancer. If the OR > 1 → • The alternative hypothesis is referred to as the
Smoking is associated with higher odds of hypothesis of “difference”
lung cancer • There is a statistically significant difference
between the 2 variables that are being
studied
Risk: Probability of a Disease • Example: Does exercise reduce cholesterol
Outcome levels?
• Alternative hypothesis: Exercising daily has
1. Absolute risk—Ratio of the number of people an effect on cholesterol level by lowering
exposed to a risk factor that developed disease cholesterol levels.
to all of those who were exposed to the risk
factor Type I error (alpha)
• A type I error (false-positive, also known as a
Absolute risk = A / A + B
rejection error) is rejection of a null hypothe-
sis that is actually true in the population
2. Relative risk—Disease risk in the exposed • The investigator concludes that there is a sig-
group divided by disease risk in unexposed nificant difference between the groups when,
group. It can be calculated for cohort study in fact, there is no true difference
(prospective study). • This risk can be reduced by setting a more
For a rare disease, OR approximates R stringent P value (e.g., .01 instead of .05)
• A difference was seen that truly does not
Relative risk = A / ( A + B ) / C / ( C + D ) exist

Type II error (beta)
3. Attributable risk—Difference in risk between • A type II error (false negative, also known as
the exposed and unexposed groups an acceptance error) is failure to reject the
null hypothesis that is actually false
Attributable risk = A / A + B - C / C + D
• The investigator concludes that there is no
difference when a difference actually exists in
the population
Statistical Hypothesis • Increasing the sample size will reduce the
(Null Hypothesis vs. Alternative risk of these errors
Hypothesis) • A difference that was not seen but which truly
exists
Null hypothesis
• The null hypothesis is referred to as the Power of a study
hypothesis of “no difference” • The probability of rejecting the null hypoth-
• There is no statistically significant relation- esis or the probability that there is a treatment
ship between the 2 variables that are being effect (i.e., exercising daily reduces choles-
studied terol levels)
• The larger the sample size, the higher the sta- –– P ≤ 0.01: Very strong presumption against
tistical power null hypothesis
• Power = 1 minus the probability of a type II –– P ≤ 0.05: Strong presumption against null
error (beta) hypothesis
–– 0.05 < P ≤ 0.1: Low presumption against
Standard deviation (SD) null hypothesis
• A measure of the variability of individual val- –– P > 0.1: No presumption against the null
ues around the mean or average value hypothesis
• When data are grouped closely together, the
SD is small. When data are highly variable, Confidence intervals
the SD is large • A confidence interval is a range of values
• One standard deviation—68% of the num- with a specified probability that a given
bers fall within the mean (average) parameter falls in that range
• 2 standard deviations—95% of the numbers • Often 95% (P value of 0.05) or 99% (P value
fall within the mean of 0.01)
• 3 standard deviations—99.7% of the numbers • If the confidence interval includes a 0 or a 1,
fall within the mean then the null hypothesis cannot be rejected
Standard error of the mean (SEM) Intention-to-treat analysis

• Describes the variability in a distribution of • In an intention-to-treat analysis, study partic-
sample means ipants are analyzed according to their ran-
• Mathematically, it is the sample SD divided domized assignment, regardless of changes
by the square root of the sample size that may occur after randomization
• SEM = Standard deviation/sample size • Intention-to-treat analysis prevents the loss of
• So as the sample size increases, the standard statistical power that may be encountered
error decreases with a failure to complete study protocols
• SEM is a smaller number than the SD (dropout) or noncompliance
P value Number needed to treat

• The P value is the probability of obtaining a • The total number of patients who need to be
test statistic result at least as extreme as the treated to prevent an adverse event or bad
one that was actually observed, assuming that outcome
the null hypothesis is true • Number needed to treat = 1/absolute risk
• A researcher will often “reject the null reduction (ARR)
hypothesis” when the P value turns out to be • Example if the ARR is 20% then the number
less than a predetermined significance level, needed to treat = 1/0.2, which is 5. Thus 5
often 0.05 or 0.01. Such a result indicates that people need to be treated to prevent one bad
the observed result would be highly unlikely outcome
under the null hypothesis • The number needed to harm is a measure that
• Many common statistical tests, such as chi- indicates how many persons on average need
square test or Student t test, produce test sta- to be exposed to a risk factor over a specific
tistics that can be interpreted using P values period to cause harm in an average of one
• An informal interpretation of a P value, based person who would not otherwise have been
on a significance level of about 10%, might be: harmed
PEARLS AND PITFALLS paper 4: assessing harms when comparing

medical interventions: AHRQ and the effec-
• Bias is a systematic error in the design study tive health-care program. J Clin Epidemiol.
that can decrease the ability to find a relation- 2010;63(5):502–12.
ship between the exposure and the outcome Copeland-Linder N. Research and statistics: reli-
of interest. ability and validity in pediatric practice. Pediatr
• A randomized controlled study is the optimal Rev. 2009;30(7):278–9.
way to evaluate the effect of 2 different treat- Ferrante di Ruffano L, Hyde CJ, McCaffery KJ,
ments for a disease. Bossuyt PM, Deeks JJ. Assessing the value of
• Statistical significance does not imply clini- diagnostic tests: a framework for designing and
cal significance. evaluating trials. BMJ. 2012;344:e686.
• A good screening test is a rapid, inexpensive Hernandez RG, Rowe PC. Research and statistics:
assay and has a good sensitivity (i.e., a nega- cohort studies. Pediatr Rev. 2009;30(9):364–5.
tive test is reliable). Moore EM, Johnson SB. Research and statistics:
• Having a larger sample size increases the case reports, anecdotal evidence, and descrip-
power of a study. tive epidemiologic studies in pediatric practice.
• Standard deviation is a measure of the vari- Pediatr Rev. 2009;30(8):323–4.
ability of individual values around the mean Norris S, Atkins D, Bruening W, Fox S, Johnson E,
or average value. Kane R, et al. Selecting observational studies for
• A confidence interval is a range of values comparing medical interventions. In: Methods
with a specified probability that a given guide for effectiveness and comparative effec-
parameter falls in that range. tiveness reviews [Internet]. Rockville: Agency
for Healthcare Research and Quality; 2010.
Palaia A. Research and statistics: study design and
Suggested Reading data sources. Pediatr Rev. 2013;34(8):371–2.
Perry-Parrish C, Dodge R. Research and statistics:
Chou R, Aronson N, Atkins D, Ismaila AS, validity hierarchy for study design and study
Santaguida P, Smith DH, et al. AHRQ series type. Pediatr Rev. 2010;31(1):27–9.
Patient Safety and Quality
Improvement 30
Osama I. Naga
Nonpreventable medical errors

MEDICAL ERRORS • Example: Patient with no history of allergic
• A medical error is an act that has the potential reaction to penicillin develops a severe aller-
to cause patient harm, regardless of whether gic reaction to amoxicillin.
or not harm reaches the patient.
Causes of medical errors
Preventable adverse event • Inadequate or poor communication
• A medical error that results in harm to the • Insufficient information flow
patient • Human issues
• Patient issues
Potential adverse events or near misses • Workflow and staffing issues
• Medical errors that do not cause harm to the • Technical breakdowns/failures
patient • Policies and procedures that are inadequate
Types of potential adverse events or near How to address medical error

misses: • Either the medical error caused harm or not,
• Intercepted: An error that is recognized and the physician must analyze the event to pre-
corrected before it reaches the patient vent its reoccurrence and to improve the
• Nonintercepted: An error that reaches the safety system.
patient but does not result in harm • All providers must be responsible for the
quality of patient care and safety.
Preventable medical errors
• Examples: Example: A nurse administered the incorrect
–– Failure to provide preventive treatment. medication.
–– Failure to provide both the hepatitis B vac- • Investigate the flaw or problem within the
cine and hepatitis B immunoglobulin to an system that allowed or facilitated the
infant born to an HBsAg-positive mother mistake.
within 12 h. • Try to understand how and why the event
–– Patient who is allergic to penicillin is pre- occurred, instead of focusing on just blaming
scribed amoxicillin and develops a skin or punishing the nurse.
rash after drug administration. • Changing how medications are stored,
labeled, or packaged may prevent the error
O. I. Naga (*) from occurring again.
Texas Tech University Health Sciences Center, El Paso, TX, USA • This course of action does not negate the
e-mail: osama.naga@ttuhsc.edu nurse’s personal responsibility.

922 O. I. Naga
Sentinel Event • Incorrect documentation/data

• Knowledge deficit
• A sentinel event is an unexpected occurrence • Performance error and poor communication
of death or serious physical or psychological
injury. Significance
• Near miss sentinel event: If the risk and • Harm may or may not reach the patient (e.g.,
potential consequences of a recurrence may mistake caught early by physician, parents, or
lead to a serious adverse outcome. pharmacist).
• A sentinel event may or may not be due to a • The severity of harm varies from minimal to
medical error. serious adverse effects or even death.
Prevention
Root Cause Analysis (RCA) Process • Avoid abbreviations of drug names (e.g.,
“MS” may mean “morphine sulfate” or “mag-
• A process for identifying the primary or nesium sulfate”).
causal factors that underlie variation in per- • Confirm that the patient’s weight is correct
formance, including the occurrence or possi- for weight-based dosages.
ble occurrence of a sentinel event. • Ensure that the weight-based dose does not
• Once a sentinel event has been identified, exceed the recommended adult dose
investigation must be immediately under- • Identify drug allergies in patients.
taken to determine the root causes that have • Write out instructions rather than using abbre-
led to the event as well as to implement an viations, e.g., “Take 1 tablet twice a day”
action plan to monitor for and to minimize rather than “bid.” Avoid vague instructions
any future risk that this event will recur. such as “Take as directed.”
• The concentration of the medication and the
frequency of administration should be clearly
Diagnostic Errors noted on prescriptions.
• Avoid use of a terminal zero to the right of the
• Diagnostic errors in the form of missed or decimal point (e.g., use 5 rather than 5.0) to
incorrect diagnosis account for most pediatric minimize 10-fold dosing errors.
malpractice cases. • Use a zero to the left of a dose less than 1
• The most common diseases associated with (e.g., use 0.1 rather than 0.1) to avoid 10-fold
diagnostic errors: pneumonia, meningitis, dosing errors.
appendicitis, and testicular torsion. • Spell out dosage units rather than using abbre-
• Most pediatricians have at least 1 diagnostic viations (e.g., milligram or microgram rather
error per month, e.g., misdiagnosis of viral than mg or μg; units rather than “u”).
pharyngitis as acute streptococcal pharyngitis— • The pharmacist and nurse must verify all
a viral illness diagnosed as a bacterial illness. medication orders.
• When giving a verbal order, request that the
name of the medication and directions for use
Treatment Errors be read back.
Causes of medication errors Decrease the risk of medication administration

• Calculation error errors by parents
• Dosage form confusion • Liquid medications should be dosed in milli-
• Illegible handwriting liters, not teaspoons or tablespoons.
30 Patient Safety and Quality Improvement 923
• Medications should be dosed to the nearest Voluntary error reporting

0.1, 0.5, or 1 mL. • Errors reported, with little or no patient harm,
• Appropriate-volume milliliter-based dosing can provide information critical to improving
devices should be distributed with the patient safety.
medication.
–– Syringes are the preferred dosing device. Barriers to voluntary reporting
–– Measuring cups and spoons calibrated and • Fear of punitive action
marked in milliliters are acceptable • Lack of feedback
alternatives. • The incident report takes a long time to
• Advanced counseling strategies to ensure complete
parental understanding and adequate health • Lack of physician access to electronic inci-
literacy and numeracy should be offered. dent reporting systems
• Interruption of patient care to complete an
Role of the institution in reducing medication incident report
errors
• Provide education and training to hospital Factors that may enhance voluntary reporting
staff. • Education about which errors should be
• Computerized systems to check dose and reported, even if trivial or causing no harm
dosage schedules, drug interactions, allergies, • Encouraging a nonpunitive culture for report-
and duplicate therapies. ing and reviewing adverse events
• Standardize equipment (such as infusion • Feedback on a regular basis about errors
pumps and weight scales) throughout the reported and about individual events
institution. • Evidence that reporting of errors has success-
• Standardize measurement systems through- fully led to system changes
out the institution, for example, using only • Electronic format for reports
kilograms for weight, rather than using • Protecting the confidentiality of the author of
pounds in 1 department and kilograms in the incident report
another.
• Avoid use of verbal orders whenever possible. Mandatory error reporting
• Have a pharmacist participate in daily clinical • Example of mandatory reporting
rounds. –– Suspected child physical or sexual abuse
• Adjust for look-alike and sound-alike –– Deaths not related to anticipated disease
medications. progression
• Remove high-risk medications. –– Medical equipment malfunction or misuse
leading to serious patient harm or death
–– Discharge of a patient incapable of making
medical decisions to an unauthorized
REPORTING MEDICAL ERRORS person
• Reporting medical error is paramount to Medical error disclosure
establishing a system capable of preventing • Once a medical error has been detected, it
future mistakes and improving the safety of must be disclosed to the patient and
care. family.
• Both voluntary and mandatory reporting sys- • Providers should consider offering an apol-
tems will help to prevent the recurrence of a ogy, and disclosing medical errors.
similar event.
924 O. I. Naga
Policies Procedure Plant, technology
The computers are

The number of staff is not Incorrect patient far from the exam
appropriate for the demographic rooms
number of patients and information
the size of the practice. The Internet is slow
Long waiting
time in a
The rooms are far from pediatric office
The fax machine is not The staff is new and each other, and the
receiving the lab and not well trained communications between
imaging study reports staff and physicians are
The staff burnout poor
Measurement People Environment
Fig. 30.1 A fishbone diagram as used in root cause analysis can help brainstorming by team members to identify the root
cause of long wait times in a busy pediatric practice
• Patients desire and deserve disclosure of • Root cause analysis to identify problems and
errors that have caused them harm. their solutions.
• Disclosure of medical errors by physicians • For each cause found, the team should con-
helps build trust in the clinician. tinue to “drill down” by repeatedly asking
• Frank disclosure of medical errors by physi- “Why is that?” until the root causes are
cians decreases the likelihood of parents identified.
seeking legal action. • The fishbone diagram as used in root cause
analysis can help brainstorming by team
Recommendations members to identify the root causes of prob-
• Ensure that patient and family remain at the lems, leading to improvement in the quality
center of communication. of care (Fig. 30.1).
• Communicate clearly about how the medical
error occurred and what will be done to pre-
vent its recurring in the future.
• Support personnel to answer the family’s PATIENT SAFETY
questions.
• Promptly share with the family any new H andoffs
information obtained from investigation.
• Address all patient and family concerns as • A handoff takes place when a patient or a
soon as possible. patient’s medical information is transferred
from one provider to another and/or from one
healthcare venue to another.
• The resident duty hour restrictions imple-
QUALITY IMPROVEMENT (QI) mented several years ago have increased the
frequency of patient handoffs.
• To cultivate an effective team, encourage • The use of a mnemonic is recommended to
transparency, collaboration, teamwork, and structure patient handoffs. This will decrease
learning from mistakes. the risk of miscommunication and help
30 Patient Safety and Quality Improvement 925
ensure that all important elements are N ever Events

included. For example: I-PASS: Illness sever-
ity, Patient summary, Action list, Situation • Serious reportable hospital events that should
awareness and contingency plans, and never occur
Synthesis by receiver. • Serious—resulting in death or significant
• Methods of communications: disability
–– Printed patient summary documents (sign- • Should not occur:
out documents) –– Clearly identifiable and measurable
–– Verbal communication –– Usually preventable
• Use of both a sign-out document and verbal
communication together are recommended. Examples of never events
• Sign-out and verbal documents generally • Surgical event
remain accurate for only a short period –– A surgical procedure performed on the
(patient’s clinical condition may change in wrong body part
6 h or less). • Product or device event
• The ideal method of handoff is using an elec- –– Contaminated drug or instrument provided
tronic summary that is continuously updated by the healthcare setting
to reflect clinical changes. • Patient protection event
–– An adolescent with suicide attempts or
self-harm, resulting in serious disability,
Fostering a Culture of Safety while being cared for in a healthcare
facility
• Encourage communication and teamwork to • Care management event
meet high patient safety standards. –– Patient death or serious injury associated
• Provide an open, fair, and transparent envi- with a medication error (e.g., errors involv-
ronment for the disclosure of medical errors ing the wrong drug, wrong dose, wrong
to better identify means to decrease or elimi- patient, wrong time, wrong rate, wrong
nate them in the future. preparation, or wrong route of
administration)
Examples of fostering a culture of safety • Environmental event
• Use at least 2 patient identifiers when provid- –– Patient’s death due to an oxygen line
ing care, treatment, and services: designed to deliver oxygen to the patient
–– Check the patient’s name, hospital number, containing no oxygen
and date of birth on both the wristband and • Criminal event
hospital chart before obtaining blood or –– Abduction of a newborn from the newborn
administering medicine. nursery
• Report critical results of tests and diagnostic
procedures on a timely basis.
• Maintain and communicate accurate patient PEARLS AND PITFALLS
medication information:
–– Obtain a list of patient medications on • Punishing the provider for medical mistakes
admission to a healthcare facility. is not the ultimate solution; it is merely a tem-
• Identify patients at risk for suicide. porary fix. Addressing the real cause and
–– Conduct a risk assessment to identify implementing the real solution will prevent
patients at risk for suicide. the same mistake for reoccurring.
926 O. I. Naga
• Near miss: If the potential harm from a medi- Haig KM, Sutton S, Whittington J. National patient
cal error does not reach the patient. safety goals. SBAR: a shared mental model for
• Sentinel event: Medical error leading to a improving communication between clinicians.
patient’s unexpected death or serious physi- Jt Comm J Qual Patient Saf. 2006;32(3):167–75.
cal or psychological injury. Institute of Medicine (US) Committee on Quality
of Health Care in America. Crossing the quality
chasm: a new health system for the 21st century.
Suggested Reading Washington, DC: National Academies Press
(US); 2001. https://www.ncbi.nlm.nih.gov/
Bartman T, McClead RE. Principles of quality books/NBK222274/. Accessed 20 Dec 2018.
improvement and patient safety. Pediatr Rev. McClead RE, Brady M. Sentinel events/patient
2016;37(10):407–17. safety events. Pediatr Rev. 2016;37(10):448–50.
Crowley E, Williams R, Cousins D. Medication Pereira-Argenziano L, Levy FH. Patient safety and
errors in children: a descriptive summary quality improvement: terminology. Pediatr Rev.
of medication error reports submitted to the 2015;36(9):403–11.
United States Pharmacopeia. Curr Ther Res.
2001;62(9):627–40.
Pharmacology and Pain Management
31
Osama I. Naga
Table 31.1 Absorption of drugs

GENERAL PEDIATRIC Drug Drug-food interaction
PHARMACOLOGY Acetaminophen Food may delay absorption
Tetracycline, Milk and dairy products affect the
Absorption (Table 31.1) doxycycline, absorption
minocycline
Antihistamines, e.g., Food may delay the absorption
• Absorption is the process by which a drug cetirizine
enters the bloodstream or another body com- Iron Acidic juices may enhance the iron
partment from the site of administration. absorption
• Drugs administered via the intravenous (IV) Antacids interfere with iron
route are 100% bioavailable, meaning that the absorption
Levothyroxine Grapefruit, soybeans, and soy milk
entire drug dose has reached the circulation. may interfere with absorption
• Due to diminished intestinal motility and Griseofulvin Should be taken with whole milk or
delayed gastric emptying in neonates and other food containing fat for
infants, it takes longer for a drug to reach a optimum bioavailability
similar plasma concentration as in older chil- NSAIDs, e.g., Food or milk may prevent stomach
ibuprofen irritation
dren after oral administration.
NSAID Nonsteroidal anti-inflammatory drugs
Bioavailability Hepatic Metabolism

• Bioavailability is defined as the rate and • The cytochrome P450 (CYP) isoenzymes in
extent to which the active drug is absorbed the liver, primarily 3A4, 2D6, 1A2, 2C9, and
and becomes available at the site of drug 2C19, are responsible for the oxidation of
action to produce a pharmacologic response 75% of all drugs (Table 31.2)
O. I. Naga (*)

928 O. I. Naga
Table 31.2 Cytochrome P450 (CYP) enzyme inhibitors • Patients with lower muscle mass (e.g., neo-
and inducers and potential interactions nates, females, malnourished patients).
Cytochrome P450 (CYP) enzyme Potential interactions • Patients with vomiting and diarrhea, or dehy-
inhibitors drated, and at the same time using diuretics
Amiodarone, cimetidine, May increase the risk
fluconazole, fluoxetine, of toxicity when
may develop increased serum drug concen-
metronidazole, trimethoprim/ combined with certain trations with routine dosing and potential
sulfamethoxazole, drugs, e.g., attainment of a toxic level.
diphenhydramine, clarithromycin, methotrexate, • The dosing interval of renally eliminated
itraconazole, erythromycin tacrolimus drugs, e.g., gentamicin or vancomycin, may
Cytochrome P450 (CYP) enzyme Potential interactions
inducers need to be prolonged when coadministered
Carbamazepine, phenobarbital, Decrease the activity with ibuprofen or indomethacin or in neo-
rifampin, glucocorticoids of certain drugs, e.g., nates with a history of birth hypoxia/asphyxia
warfarin, digoxin, and or cyanotic congenital heart disease.
oral contraceptives
• A postoperative cardiac patient who has poor
renal perfusion and who requires antibiotics
Drug-Drug Interactions for concerns of sepsis may require a less fre-
quent dosing interval for vancomycin, an
• Pediatricians should screen routinely for antibiotic that is cleared renally.
potential drug-drug, drug-herbal product, or
drug-food interactions before prescribing a Methods of dose adjustment clinically
new medication, e.g.: • Trough level (Fig. 31.1)
–– Beta-blocker prescribed for hypertension –– The lowest concentration reached by a
or migraines inhibits the activity of a beta drug before the next dose is administered.
agonist given to treat an asthma –– Trough routinely used for certain drug mon-
exacerbation itoring, e.g., gentamicin, or vancomycin.
–– The effect of a broad-spectrum antibiotic –– Trough concentrations are obtained at the
on warfarin by eradicating the gut flora end of a dosing interval just before the next
needed to metabolize the anticoagulant dose is administered to verify that the
–– Increased potential toxicity of phenytoin drug’s concentration is still in the thera-
when combined with sulfa drugs, e.g., tri- peutic range and to prevent drug toxicity.
methoprim/sulfamethoxazole –– If the first trough level obtained is accept-
able, repeat the trough levels at 4–6 days
into therapy to ensure nontoxic level.
Renal Elimination –– If the trough level is higher than accept-
able, the drug should not be given, and
Examples of drugs predominantly eliminated another level checked 6 h later. This should
by the kidneys: be repeated as needed until a safe level is
• NSAIDs, angiotensin-converting enzyme obtained.
inhibitors, angiotensin II receptor blockers, • Peak level (see Fig. 31.1)
aminoglycosides, sulfamethoxazole/trime- –– The highest concentration reached by a
thoprim, vancomycin, ciprofloxacin, antivi- drug after the dose is administered
rals, amphotericin B –– Peak level should be obtained 30 min after
the infusion of gentamicin or vancomycin
Dose adjustment of renally eliminated medica-
–– Peak levels are not necessary for cases
tions, e.g.:
being treated with a course of antibiotics
• Patients with primary pathologic kidney
without a positive culture
disease.
31 Pharmacology and Pain Management 929
Fig. 31.1 Trough, peak,

and steady-state levels of Peak after the dose is administered
a drug curve
Steady state
level
Trough before the next dose
Drug dosing intervals
–– If a blood culture is positive and an organ- Table 31.3 Examples of t½ and drug dosing intervals
ism and sensitivities are identified, both Drug Half-life (t½) Drug-dosing intervals
peak and trough levels should be obtained Adenosine < 10 s Give all doses with a
to ensure adequate dosing rapid IV push
Morphine 2–3 h Doses every 3–4 h as
• Creatinine and glomerular filtration rate
needed
–– Creatinine clearance and glomerular filtra- Propranolol 4–6 h Doses can be divided
tion rate are used for adjustment of dosage every 6–8 h
of renally eliminated medications Fluoxetine 4–6 days Once a day
Levothyroxine 6–7 days Once a day
Amiodarone 60 days Once a day (oral
approximately form)
Half-Life (t½) IV intravenous
• t½ is the time it takes the plasma concentra- –– Gentamicin trough level usually measured
tion of a drug to decrease by half. before second dose when the drug reaches
• 50% of the drug will remain after 1 t½, 25% steady state level (Time to Steady State:
will remain after 2 t½, 12.5% after 3 t½, 20–40 h) in neonates
6.25% after 4 t½, and 3.125 after 5 t½. Thus,
approximately 97% of the drug will have left
the system after 5 t½. ractical advice when Prescribing
P
• The t½ can vary from hours to days and even Medications
months among different medications.
• Half-life informs our decisions related to • When prescribing for children, it is appropri-
drug-dosing intervals to maximize efficacy ate to use a pediatric reference source
and limit toxicity (Table 31.3). • An incorrect dose, particularly in infants,
• To achieve a steady state with drug concen- could have catastrophic adverse effects
tration greater than 97% requires 5 t½; drug • It is good practice for two people to double
must be administered at constant intervals. check dose calculations, such as the pre-
• When measuring drug levels, proper timing is scriber and dispensing pharmacist
essential for accurate therapeutic monitoring, • Usually, the calculated dose should not
e.g.: (see Fig. 31.1): exceed the adult dose
–– Vancomycin trough level usually measured • The recommended dose may not be the opti-
before third or fourth dose when the drug mum dose for some children. It may then be
reaches steady state level (Time to Steady necessary to adjust the dose according to the
State: 18–39 h) in infants and children clinical response
930 O. I. Naga
• Ensure that the calculated dose can be admin- Drug activity

istered safely to the child • Against aerobic Gram-negative organism,
• Doses can be rounded to ensure that parents e.g., Yersinia pestis (plague), Francisella
can accurately measure them tularensis (tularemia)
• Some activity against Staphylococcal spe-
cies, Mycobacterium, Entamoeba histolytica,
Drug Reactions Cryptosporidium parvum
• Immunologic reactions include (see also Drug toxicity

Chap. 11 “Allergy and Immunology”) • Nephrotoxicity and ototoxicity
–– Type I (E-mediated)
–– Type II (cytotoxic)
–– Type III (immune complex) Beta Lactam Antibiotics
–– Type IV (delayed)
• Nonimmunologic drug reactions include: Classes of beta lactam antibiotics
–– Pseudo-allergic reactions caused by • Penicillins
direct mast cell degranulation, e.g., red • Cephalosporins
man syndrome with an infusion of • Carbapenems
vancomycin • Monobactams
–– Idiosyncratic reactions, e.g., drug-induced
hemolysis in patients with glucose-6-phos- Mechanism of action
phate dehydrogenase deficiency and aspi- • Inhibit cell wall synthesis by binding and
rin sensitivity causing bronchospasm inhibiting cell wall proteins called penicillin-
binding proteins (PBPs)
he FDA Adverse Event Reporting

T
Penicillins, e.g., Crystalline Penicillin
System (FAERS)
Indications
• Example of cases that should be reported to
• Periodontal infections
the U.S. Food and Drug Administration
• Erysipeloid
(FDA): A serious adverse drug event:
• Group A and group B streptococci
–– Death
• Syphilis
–– Hospitalization
• Meningococcal meningitis and
–– Disability
meningococcemia
–– Birth defect
Ampicillin
ANTIBIOTICS
Bacterial coverage
minoglycosides, e.g., Gentamicin,
A • Similar to penicillin, but its spectrum extends
Tobramycin, and Amikacin to some Gram-negative bacteria
Mechanism of action Indications

• Inhibit bacterial protein synthesis by binding • Listeria monocytogenes meningitis
to bacterial 30S ribosome • Enterococcal infections
• UTIs caused by susceptible strains of ◦◦ Many Gram-positive cocci, including

Escherichia coli MSSA and most Streptococcus
◦◦ No reliable CNS penetration; do not use
for meningitis or arteriovenous (AV)
Amoxicillin-Clavulanate (Augmentin; shunt infections.
GlaxoSmithKline) –– Indications
◦◦ Skin and soft tissue infection
Bacterial coverage • Second-generation cephalosporins, e.g., cefa-
• Addition of beta-lactamase inhibitors increase clor, cefoxitin, cefuroxime, and cefotetan
coverage to MSSA –– Bacterial coverage
• Extended coverage for respiratory infections, ◦◦ Maintains Gram-positive activity but
e.g., sinusitis, otitis media, bronchitis less than first generation
◦◦ Greater coverage for Gram-negative
Drug of choice for bite wounds bacteria than first generation, e.g., H.
• Pasteurella is susceptible to penicillin. influenzae, Enterobacter aerogenes, and
• Pasteurella and S. aureus are the likely organ- some Neisseria
isms in most animal bites. ◦◦ Extends the coverage to respiratory
Gram-negative, e.g., H. influenzae and
Moraxella
Penicillinase-Resistant Penicillins, ◦◦ Has variable activity against gut anaer-
e.g., Nafcillin or Oxacillin obes except cefuroxime
◦◦ Not used for meningitis
• Drug of choice only for staphylococcal infec-
–– Indications
tion (MSSA), but the resistance is rapidly
◦◦ Abdominal surgeries
expanding.
◦◦ Community-acquired pneumonia
◦◦ Pelvic inflammatory disease
• Third-generation cephalosporins
nti-Pseudomonal Penicillins, e.g.,
A
–– Bacterial coverage
Piperacillin and Ticarcillin ◦◦ Extended Gram-negative activity, loss of
Gram-positive activity
Bacterial coverage
◦◦ Good cerebrospinal fluid (CSF)
• Extended Gram-negative coverage, including
penetration
Pseudomonas species, S. aureus, and H.
◦◦ Has greater activity in deep tissue infec-
influenzae
tions and less toxicity than
• Addition of beta-lactamase inhibitors:
aminoglycosides
–– Piperacillin-tazobactam (Zosyn; Pfizer)
◦◦ Only few drugs are active against P.
• Drug of choice, e.g., Pseudomonas
aeruginosa, e.g., ceftazidime
aeruginosa
–– Ceftriaxone
◦◦ Has the longest half-life and effective
Cephalosporins against most S. pneumoniae
◦◦ Crosses the blood-brain barrier and indi-
(Penicillinase-Resistant)
cated as the primary therapy for
• First-generation cephalosporin, e.g., cefazo- meningitis
lin and cephalexin ◦◦ Ceftriaxone can be used as a single agent
–– Bacterial coverage for empiric treatment of meningitis
932 O. I. Naga
while lab results are pending; except in Monobactam, e.g., Aztreonam

neonates, ampicillin needs to be added
to cover for Listeria • Aztreonam is often used in patients who are
–– Cefotaxime allergic to penicillin or who cannot tolerate
◦◦ Bacterial coverage is the same as aminoglycosides.
ceftriaxone • Aztreonam has strong activity against suscep-
◦◦ Preferred in neonates or < 30 days old tible aerobic and facultative Gram-negative
• Fourth-generation cephalosporin, e.g., bacteria, including P. aeruginosa and most
cefepime Enterobacteriaceae.
–– Bacterial coverage • Aztreonam is not active against Gram-
◦◦ Equal Gram-positive as the first-genera- positive cocci or anaerobes.
tion cephalosporins
◦◦ Equal Gram-negative as the third-gener-
ation cephalosporins Other Commonly Used Antibiotics
◦◦ Excellent Pseudomonas coverage
• Fifth-generation cephalosporin, e.g., Clindamycin
ceftaroline
–– Bacterial coverage Mechanism of action
◦◦ Increased Gram-positive coverage, some • Inhibits bacterial protein synthesis by binding
Gram-negative to 50S ribosomal subunit.
◦◦ U.S. Food and Drug Administration
Bacterial coverage
(FDA) approved for community-
• Active against many strains of MRSA
acquired pneumonia and skin/soft tissue
• Active against anaerobes
infections, including MRSA for infants
• Active against most staphylococcal and strep-
and children > 2 months of age
tococcal infections
Adverse effects
arbapenems, e.g., Imipenem/
C
• Diarrhea, including C. difficile enterocolitis
Cilastatin, Meropenem,
and Ertapenem
acrolides, e.g., Azithromycin
M
• Imipenem is a very broad-spectrum carbape- and Clarithromycin
nem antibiotic.
• Very active against Bacteroides fragilis. Mechanism of action
• Kills most Enterobacteriaceae, Pseudomonas, • Inhibits bacterial protein synthesis by binding
and Gram-positive bacteria and is inhibitory to 50S ribosomes
for Listeria and Enterococcus faecalis. • Azithromycin does not inhibit cytochrome
• Imipenem can lower the seizure threshold P-450 as erythromycin or clarithromycin do
and should not be used in patients with sei-
zures or renal insufficiency. Bacterial coverage
• Meropenem is a carbapenem with a longer • Azithromycin is the drug of choice for pertus-
half-life, less likely than imipenem to cause sis, Mycoplasma, and Chlamydia
seizures.
• Ertapenem has limited activity against Adverse effects
Enterococcus sp. and P. aeruginosa. • Gastrointestinal (GI) irritation
• Hypertrophic pyloric stenosis if used in chil- Tetracycline

dren less than 1 month of age
Bacterial coverage
• Tetracycline provides coverage against tick-
Rifampin borne organisms, e.g., Lyme disease, Rocky
Mountain spotted fever
Bacterial coverage • Doxycycline and minocycline are used for
• Tuberculosis acne (Propionibacterium acnes)
• Invasive H. influenzae • Doxycycline may also treat MRSA
Indications Adverse effects
• Close contacts to a child who has invasive • Tetracycline causes staining of dental
meningococcal infection. enamel
• Combination with vancomycin in certain • Tetracycline is not recommended in children
staphylococcal infections (ventriculoperito- less than 8 years old
neal (VP) shunt, osteomyelitis, endocarditis) • Tetracycline can be used in children younger
• Persistent group A streptococcal pharyngitis than 8 years in life-threatening situations,
in combination with beta-lactam antibiotics e.g., Rocky Mountain spotted fever (doxycy-
• MRSA carriage eradication attempt cline is the drug of choice)
• Doxycycline does not cause staining of per-
manent teeth compared to tetracycline
Fluoroquinolones, e.g., Ciprofloxacin
AAP recommendation of fluoroquinolones use
rimethoprim/Sulfamethoxazole
T
in children
• If the pathogen is multidrug resistant Bacterial coverage
• No safe and other effective alternative • Pneumocystis jiroveci pneumonia, which is
• Parenteral therapy is not feasible common in immunocompromised patients,
• No other effective alternative oral agents e.g., HIV
• Urinary tract infection, treatment, and pro-
Bacterial coverage
phylaxis (one drug of choice in susceptible
• UTIs caused by multidrug resistant Gram-
patients)
negatives rods
• MRSA infection.
• Resistant Gram-negative rods:
• Gastroenteritis due to Salmonella, Shigella,
–– P. aeruginosa
and Isospora belli
–– GI and respiratory tract infection
• Burkholderia cepacia.
–– Chronic or acute osteomyelitis
• Brucella.
Adverse effects Adverse effects

• Fluoroquinolones in children cause arthralgia • Rash
that resolves after drug withdrawal. • Neutropenia
• Tendon rupture, especially Achilles tendon • Stevens–Johnson syndrome
and often bilateral, is a rare complication
(1 in 5000)
934 O. I. Naga
Vancomycin Adverse effects

• Red man syndrome, or red neck syndrome
Mechanism of action –– Vancomycin releases histamine that can cause
• Inhibits bacterial cell wall synthesis by bind- pruritus and erythema of the head and neck.
ing tightly to peptidoglycan precursors and –– This is a related drug infusion problem; just
blocking polymerization slow down the infusion rate.
• Ototoxicity and nephrotoxicity (monitor drug
Bacterial coverage toxicity with trough levels)
• Confirmed Gram-positive infection in patient • Misuse of vancomycin can cause develop-
seriously ill or allergic to beta-lactam ment of resistance
antibiotics
• Initial empiric treatment in a child Indications
(> 2 months) with meningitis in combination • C. difficile diarrhea (given orally, not system-
with third-generation cephalosporin ically absorbed)
• MRSA infection • S. aureus infections, including MRSA
• Prophylaxis before prosthetic device implan-
tation requiring major surgery Summary of antibiotics and adverse reactions
• Enterally for C. difficile (Table 31.4).
• Acute infectious endocarditis if S. aureus is
the likely cause
Table 31.4 Antibiotics and common adverse effects

Commonly used antibiotics Common adverse effects Comments
Penicillins, e.g., amoxicillin, Non-IgE-mediated: vomiting, diarrhea, Most cases of penicillin allergies are
amoxicillin/clavulanic acid headache, or a non-urticarial, nonpruritic non-IgE-mediated
(Augmentin; GSK), piperacillin/ rash
tazobactam (Zosyn; Pfizer) IgE-mediated type1 hypersensitivity: Desensitization is necessary for pregnant
urticarial rash, angioedema, anaphylaxis with neurosyphilis, congenital syphilis, or
(0.3–3%) tertiary syphilis
Cephalosporins, e.g., Nausea, vomiting, diarrhea, rash, AST Low risk of allergic reaction to first-
cephalexin, cefazolin, and ALT elevation, allergic reaction. generation cephalosporins in penicillin-
cefuroxime, cefdinir, cefixime, allergic patients (3–7%) and much lower risk
ceftriaxone for third-generation cephalosporins
Aminoglycosides, e.g., Nephrotoxicity/ototoxicity Monitor toxicity with trough levels, renal
gentamicin, tobramycin function, and audiology testing
Glycopeptides, e.g., vancomycin Red man syndrome; pruritic Reduce IV infusion rate (infusion-related
erythematous rash, and flushing reaction)
Antituberculosis drugs, e.g., Nausea, vomiting, diarrhea, anorexia, Vitamin B6 (pyridoxine) ➔ prevents
rifampin, isoniazid, hemolytic anemia, liver toxicity, peripheral neuropathy with isoniazid
pyrazinamide, ethambutol peripheral neuropathy
Orange body fluids (rifampin)
Macrolides, e.g., erythromycin, Nausea, vomiting, abdominal pain, Coated or delayed-release pill should not be
azithromycin, clarithromycin diarrhea, anorexia, taste changes opened, chewed, or crushed
(clarithromycin)
Sulfonamides, e.g., Nausea/vomiting, diarrhea, anorexia, Sunscreen, sun avoidance, and protective
trimethoprim-sulfamethoxazole, abdominal pain, rash, photosensitivity, clothing are recommended
sulfadiazine (Bactrim; Roche) headache, dizziness
Tetracyclines, e.g., tetracycline, Nausea, vomiting, diarrhea, anorexia, Sunscreen, sun avoidance, and protective
doxycycline, minocycline abdominal pain, photosensitivity, tooth clothing are recommended
discoloration in children < 8 years Give at any age to children with suspected
RMSF
IgE Immunoglobulin E, AST aspartate aminotransferase, ALT alanine aminotransferase, RMSF Rocky Mountain spotted
fever
ANTIVIRALS cyte-macrophage colony-

stimulating factor
(GM-CSF)
Acyclovir
Foscarnet
Mechanism of action
• Terminates the viral deoxyribonucleic acid • CMV infection
(DNA) synthesis when incorporated into the
viral DNA chain
Other Antiviral Agents, Against DNA
Appropriate use Viruses
• HSV type 1 and HSV type 2
• Varicella • Famciclovir, valganciclovir, penciclovir, and
• Treatment of recurrent primary genital HSV2 cidofovir
or primary HSV1 mucocutaneous infections
• Intravenous (IV) acyclovir is the drug of
choice for treatment of HSV encephalitis. Nucleoside Reverse Transcriptase
Inhibitors (NRTI)
Major adverse effects
• Acute renal failure due to precipitation in the Mechanism of action
renal tubules (proper hydration and slower • These drugs inhibit replication of HIV by
infusion can minimize this problem) interfering with the reverse transcriptase
• Nausea, vomiting, and diarrhea enzyme
Indication
Valacyclovir • HIV infection
Background Examples of NRTIs and side effects (Table 31.5)

• Newer potent oral antiviral (Inhibits DNA • Zidovudine (ZDV)
polymerase; incorporates into viral DNA) –– Significant adverse effect: Bone marrow
suppression
Indications
• HSV1 Table 31.5 Adverse effects of common antiretroviral
medications
• HSV2
• Varicella-Zoster virus (VZV) Common
antiretroviral
therapy Common adverse effects
Zidovudine Bone marrow suppression
anciclovir (IV) and Valganciclovir
G Tenofovir Nausea, vomiting, diarrhea
(Oral) Emtricitabine Headache, insomnia, diarrhea,
nausea, skin discoloration
Indications Lamivudine Headache, nausea, less common;
pancreatitis
• Congenital and acquired cytomegalovirus Indinavir Nausea, abdominal pain,
(CMV) infection hyperbilirubinemia, nephrolithiasis
Ritonavir Nausea, headache, vomiting, taste
Major adverse effects of ganciclovir and aversion
valganciclovir Fosamprenavir Nausea, vomiting, perioral
• Neutropenia and other cytopenias that may paresthesias, rash, lipid
abnormalities
interrupt therapy or require granulocyte col- Raltegravir Nausea, headache, dizziness,
ony-stimulating factor (G-CSF) or granulo- diarrhea, fatigue
936 O. I. Naga
• Didanosine (ddI) Examples of protease inhibitors and side effects

–– Significant adverse effects: Pancreatitis • Ritonavir: boosts concentration of other pro-
and peripheral neuropathy tease inhibitors
• Stavudine (d4T) –– Adverse effect: hyperlipidemia
–– Contraindication: Cannot be combined • Nelfinavir
with ddI in pregnant women; can cause –– Adverse effects: diarrhea and nausea
fatal lactic acidosis • Lopinavir
–– Adverse effects: Pancreatitis and periph- –– Adverse effect: insulin resistance
eral neuropathy • Atazanavir
• Abacavir –– Adverse effect: proximal tubulopathy (renal)
–– Most serious adverse effect is fatal • Darunavir
hypersensitivity –– Adverse effects: rash and nausea
Nonnucleoside Reverse ANTIPARASITICS (TABLE 31.6)

Transcriptase Inhibitors (NNRTI)
Permethrin
Indication
• HIV infection • Excellent safety profile
• 5% permethrin cream is the drug of choice
Examples of NNRTIs and side effects for treatment of scabies
• Efavirenz: safe in first trimester pregnancy • 1% permethrin topical solution is effective
–– Adverse effects: neuropsychiatric effects, for head lice
QT prolongation • Paralyzes the parasite to cause death
• Nevirapine: prevents mother-to-child • Not recommended in infants younger than
transmission 2 months and during pregnancy
–– Adverse effect: Rash
Malathion
Protease Inhibitors
• The most effective drug in the treatment of
Mechanism of action pediculosis or head lice
• Inhibit the HIV protease enzyme that is • Ovicidal activity
involved with processing the completed virus • Single topical application is effective in
resistant cases
Indication
• HIV infection
Table 31.6 Indications and adverse effects of common antiparasitic medications

Antiparasitic Indications Adverse effects
Albendazole/ Ascariasis, hookworms, enterobiasis, Headache, abdominal pain, reversible alopecia,
mebendazole trichuriasis, trichinosis, toxocariasis elevated liver enzymes, leukopenia
Ivermectin Cutaneous larva migrans, strongyloidiasis, Pruritus, fever, rash, myalgia, headache,
scabies constipation, diarrhea, abdominal distension
Praziquantel Schistosomiasis, taeniasis, diphyllobothriasis Loss of appetite, dizziness, drowsiness, headache,
malaise
Metronidazole Adverse effects

• GI upset, headache, dizziness, blurred vision,
Mechanism of action insomnia, and pruritus
• Metronidazole is nitroimidazole bactericidal
drug
ther Antimalarials: Atovaquone/
O
Indications Proguanil, Doxycycline,
• Anaerobic bacteria and Mefloquine
• Clostridium difficile
• Trichomonas vaginalis • Commonly used for prophylaxis for malaria
• Gardnerella vaginalis in chloroquine-resistant regions, e.g., Africa
• Treponema pallidum and the Middle East
• Oral spirochetes • Mefloquine has FDA black box warning;
• Helicobacter pylori causes psychosis
Chloroquine (Table 31.7) ANTIFUNGALS (TABLE 31.8)

Indication mphotericin B
A
• Drug of choice for malaria prophylaxis in the
sensitive chloroquine regions, e.g., Central Indication
and South America • Active against broad array of fungi, e.g.,
• Drug should be administered 1–2 weeks Candida, Aspergillus, Zygomycetes,
before traveling Histoplasma, Coccidioides immitis
Table 31.7 Indications, and side effects of common antiprotozoal medications

Antiprotozoal Indications Adverse effects
Atovaquone-proguanil Chloroquine-resistant malaria or Abdominal pain, elevated liver enzymes,
(Malarone; GSK) unknown resistance regions headache, vomiting, asthenia
Chloroquine phosphate Chloroquine-sensitive malaria Macular degeneration, psychosis, agitation,
regions nausea, vomiting, abdominal pain
Hydroxychloroquine Chloroquine-sensitive malaria Rash, pruritus, skin pigmentation, alopecia,
regions abdominal pain, diarrhea, anorexia
Table 31.8 Indications, monitoring of toxicity and adverse effects of common antifungal drugs
Antifungal Indications Monitoring and adverse effects
Amphotericin B Mucocutaneous candidiasis, systemic Hypokalemia, hypomagnesemia
candida, Aspergillus and Cryptococcus Monitor electrolytes, hematologic, renal, and liver
species function
Terbinafine Tinea capitis, tinea corporis, tinea pedis, AST, ALT; do not use if liver dysfunction
tinea cruris, onychomycosis
Griseofulvin Tinea capitis, tinea corporis, tinea pedis, No monitoring is required
tinea cruris
Fluconazole Tinea capitis, tinea corporis, tinea pedis, Liver function test; exercise caution if liver dysfunction
tinea cruris, mucocutaneous candidiasis
Nystatin suspension Mucocutaneous candidiasis Nausea, vomiting, abdominal pain, diarrhea
AST aspartate aminotransferase, ALT alanine aminotransferase
938 O. I. Naga
Toxicity Table 31.9 Difference between furosemide, hydrochloro-

• Febrile drug reaction thiazide, and spironolactone diuretics
• Hypokalemia Furosemide Hydrochlorothiazide Spironolactone
• Hypomagnesemia Hypokalemia Hypokalemia Hyperkalemia
Metabolic Metabolic alkalosis Metabolic
• Nephrotoxicity (liposomal preparation is alkalosis acidosis
equally effective and less nephrotoxic) Hypocalcemia Hypercalcemia Increases
testosterone
clearance
Fluconazole
• Hypocalcemia
Indications • Hyperuricemia
• As equally effective as amphotericin B for • Ototoxicity
treatment of invasive Candida albicans in • Nephrotoxicity
neonates
• Treatment of oropharyngeal or esophageal
candidiasis in immunocompromised patients T hiazide Diuretics
• Treatment of vulvovaginal Candida (Hydrochlorothiazide)
• Treatment of cryptococcal meningitis
• Thiazide diuretic inhibits sodium reabsorp-
tion in distal renal tubules, resulting in
Griseofulvin increased excretion of water, sodium, potas-
sium, and hydrogen.
• Standard first-line therapy for tinea capitis
• No laboratory assessment of hepatic enzyme Adverse effects
if used < 8 weeks • Hyponatremia
• Serum liver enzyme monitoring every • Hypochloremia
8 weeks; prolonged therapy is a risk of • Hypercalcemia
hepatotoxicity • Hyperuricemia
• Consumed with fatty meals, e.g., peanut but-
ter, for maximum absorption
Spironolactone
DIURETICS • Aldosterone antagonist with a diuretic and anti-

hypertensive effects; competitive binding of
Furosemide (Table 31.9) receptors at aldosterone- dependent Na-K
exchange site in distal tubules results in
• Loop diuretic: Inhibits reabsorption of sodium increased excretion of sodium, chloride, and
and chloride ions at proximal and distal renal water and retention of potassium and hydrogen
tubules and the loop of Henle by interfering • Increases testosterone clearance and estradiol
with chloride-binding cotransport system, production; blocks conversion of potent
resulting in increased excretion of water, cal- androgens to weaker ones in peripheral
cium, magnesium, sodium, and chloride tissues
Adverse effects Adverse effects

• Hypochloremia • Hyperkalemia
• Hypokalemia • Metabolic acidosis
• Alkalosis • Gynecomastia
Acetazolamide Teething
• Carbonic anhydrase inhibitor that decreases Benzocaine
the rate of aqueous humor formation, in that • Benzocaine gels and liquids for mouth and
way decreasing intraocular pressure gum pain have been linked to methemoglo-
• Inhibits hydrogen ion excretion in renal binemia, which causes a reduction in blood
tubule, increasing sodium, potassium, bicar- oxygen and can be fatal.
bonate, and water excretion and producing • All other oral health products with benzo-
alkaline diuresis caine are contraindicated for children less
than 2 years for teething relief.
• Instead of teething gels or tablets, the American
Mannitol Academy of Pediatrics recommends gently rub-
bing or massaging the child’s gums with a fin-
• Osmotic diuretic causes diuresis ger and giving the child a cool (not cold) teething
• Reduces the intracranial pressure and intra- ring or a clean, wet, cool washcloth to chew on.
ocular pressure
ANTIHYPERTENSIVE
OVER-THE-COUNTER MEDICATIONS (TABLE 31.11)
MEDICATIONS
Propranolol, Atenolol, Metoprolol
ough and Cold Products
C
(Table 31.10) Common Uses
• Hypertension
• Nonprescription (over-the-counter [OTC]) • Supraventricular tachycardia (SVT)
and prescription cough and cold prepara-
tions have not been adequately studied in Propranolol for treatment of infantile
children younger than 6 years of age, and hemangioma
thus they are not recommended for treating • Starting dose at 1 mg/kg/day divided q 8 h
the common cold symptoms in young and check heart rate and blood pressure 1and
children 2 h after the first dose
Table 31.10 Side effects of over the counter common cold and allergy medications
Cough and cold remedies Brand name Adverse effects
Diphenhydramine Benadryl (J&J) Hypertension, tachycardia, confusion, constipation, diarrhea,
paresthesia
Brompheniramine/ Bromfed DM Sedation, potential abuse, palpitations, anxiety, hypotension,
dextromethorphan/ (Morton Grove urticaria, diplopia
pseudoephedrine Pharmaceuticals)
Dextromethorphan Robitussin (Pfizer) Hallucinations, stupor, nystagmus, dystonia, seizures,
(Delsym) tachycardia, respiratory depression, coma, potential abuse
Guaifenesin Mucinex (Reckitt Nausea, vomiting, diarrhea, abdominal pain, kidney stones
Benckiser)
Phenylephrine Sudafed PE (J&J) Hypertension, chest pain, bradycardia, peripheral
vasoconstriction, arrhythmias, respiratory depression,
hallucinations
Pseudoephedrine Children’s Sudafed Palpitations, tachycardia, bradycardia, nausea, insomnia,
(J&J) dizziness, psychosis, urticaria
940 O. I. Naga
Table 31.11 Classes, and mechanism of action of antihypertensive agents

Class Antihypertensive agent Mechanism of action
Angiotensin-converting enzyme Captopril Blocks the conversion of angiotensin I to
(ACE) inhibitor Enalapril angiotensin II and the degradation of the
Lisinopril (> 6 years of age) vasodilatory molecule bradykinin through the
blockade of the kinin-kallikrein system
Angiotensin receptor blocker Irbesartan Blocks the binding of angiotensin II to type 1
(ARB) Losartan angiotensin II receptors
Calcium channel blocker (CCB) Amlodipine Lowers blood pressure by blocking the influx of
Felodipine calcium into smooth muscle, resulting in
Isradipine arteriole dilatation and reduced peripheral
Nifedipine XR resistance
β-Blocker Atenolol Decreases blood pressure through several
Metoprolol different mechanisms, including inhibition of
Propranolol renin secretion, reduction of peripheral
Labetalol resistance, lowering of cardiac output, and
decreasing plasma volume
Diuretic Hydrochlorothiazide Lowers blood pressure by decreasing plasma
Furosemide volume and lowering peripheral resistance
Spironolactone
Central α-blocker Clonidine Centrally acting α2-agonist that stimulates
α2-receptors to lower peripheral resistance and
heart rate
Vasodilator Hydralazine Acts directly on vascular smooth muscle to
Minoxidil reduce vascular wall tension and peripheral
vascular resistance
• Increase the dose gradually every 3–7 days to • Examples of these medications include raniti-
therapeutic dose 2 mg/kg/day divided q 8 h dine, famotidine, cimetidine, and nizatidine
• Monitor heart rate and blood pressure • Ranitidine reaches a peak plasma concentra-
tion 2.5 h after ingestion in children and has a
Adverse effects half-life of 6 h
• Bradycardia • H2RAs are considered safe for use in chil-
• Hypotension dren and are commonly used as first-line ther-
• Hypoglycemia (hypoglycemia-induced apy in infants
seizures)
• bronchospasm Adverse effects
• Depression • Irritability, head banging, and headaches
• Cimetidine use is associated with
gynecomastia
ANTI-ULCERS • Tachyphylaxis has been observed with
chronic H2RA use
H2-Blocking Drugs
• Histamine-2 receptor antagonists (H2RAs) P roton Pump Inhibitors (PPIs)
decrease acid production by binding to the
histamine-2 receptor on the gastric parietal • PPIs suppress gastric acid production by irre-
cell versibly blocking H+ and K+ ATPase, which is
the final step in parietal cell acid secretion.
• PPIs are more effective than H2RAs in block- –– Side effects: dizziness, headache and extra-
ing acid production. pyramidal symptoms to include dystonia
• PPIs must be given daily before meals and and tardive dyskinesia
can take several days for maximal acid sup-
pression effect.
• Examples: omeprazole, lansoprazole, and SEDATION
esomeprazole.
Minimal Sedation (Anxiolysis)
Adverse effects
• Headache, diarrhea, constipation, and nausea • Anxiolysis with the maintenance of
• In neonates, acid suppression is associated consciousness
with a higher carriage rate of candida and a • Example: Intranasal midazolam for short and
higher incidence of necrotizing enterocolitis brief procedures e.g., laceration repair in a
child who is crying and very anxious
ANTIEMETICS
Moderate Sedation (Conscious
• 5-hydroxytryptamine (serotonin) receptor Sedation)
antagonist
–– Example: Ondansetron • Controlled depressed consciousness
–– Routine use of ondansetron does not • Airway reflexes and airway patency are
improve the outcome in children without maintained
dehydration • Patient responds appropriately to age-appro-
–– Side effects: headache, dizziness, and con- priate commands (“Open your mouth”) and
stipation. The most worrisome side effect to touch
is QT-prolongation, it should be avoided in
patients with known prolonged QTc
• Antihistamines Deep Sedation
–– Examples: Diphenhydramine, meclizine,
promethazine • Controlled depressed consciousness
–– H1-antagonist and has limited dopaminer- • Airway reflexes and airway patency may not
gic (D2) effects be maintained
–– Side effect: sedation • Ability to independently maintain ventilatory
• Muscarinic M1 receptor antagonist function may be impaired
–– Example: Hyoscine (also known as • Patient not easily aroused but responds pur-
scopolamine) posefully following repeated or painful
–– Used to treat motion sickness or prophy- stimulation
lactically in the perioperative setting
–– Side effects: dry mouth, vision changes, or
drowsiness General Anesthesia
• Dopamine receptor antagonist (D2)
• Loss of consciousness occurs.
–– Example: Metoclopramide
• Impaired airway reflexes, airway patency,
–– Metoclopramide has significant promotil-
and ventilatory function.
ity effects and can increase gastric
• Children are not arousable.
emptying
• Not responsive to painful stimulation.
942 O. I. Naga
Recommendations for fasting or nothing by • Causes amnesia

mouth (NPO) before sedation and anesthesia • Mild depression of hypoxic ventilatory drive
• 2 hours fasting for clear liquids
• 4 hours fasting for breast milk Ketamine
• 6 hours fasting for formula • Commonly used for procedural sedation
• 8 hours fasting for solids • Preserves the airway reflexes
• Minimal effect on the respiratory drive
• Bronchodilatory effects and is especially
Medications for Procedural Sedation effective with bronchospasms
• Good safety profile in children
• Opioid analgesics ➔ morphine sulfate,
fentanyl Propofol
• Benzodiazepines ➔ midazolam, diazepam • A purely sedative agent without any analge-
• Barbiturates ➔ pentobarbital, methohexital, sic or amnestic properties
thiopental • Rapid onset of action (within 40 s)
• Miscellaneous agents ➔ nitrous oxide, ket- • Used for induction and maintenance of gen-
amine, propofol, dexmedetomidine eral anesthesia
• Used for procedural sedation
Morphine
• Among the oldest opioids Nitrous oxide
• Indications • Causes anxiolysis, amnesia, and mild-to-
–– Analgesia, sedation moderate analgesia.
• Side effects • Administered as an inhalant via a handheld
–– Respiratory depression, nausea and vomit- mask or mouthpiece.
ing, pruritus, constipation, miosis, toler- • Effects are rapidly lost once inhalation ceases,
ance, and physical dependence and recovery occurs within 5 min.
• Nitrous oxide has little effect on the cardio-
Fentanyl vascular and respiratory systems.
• Rapid onset of action opioid
• Most commonly used opioid for short, pain-
ful procedures Sedation Protocol
• Intranasal fentanyl is a good option for chil-
dren with severe pain seen in the emergency • Ketamine ➔ Lowest rate of adverse effects if
department and prehospital settings used alone
• Doses of fentanyl delivered via a transmuco- • Ketamine + midazolam + atropine ➔ Adding
sal route have similar analgesic action to midazolam counter the emergence delirium
intravenous opioids • Midazolam + Fentanyl ➔ High risk of respi-
• Fentanyl is preferred over morphine in ratory depression (decrease the frequency of
patients with renal insufficiency fentanyl infusion to no more than every
• Chest wall rigidity can occur with even low 3 min)
doses, especially in neonates and infants, and
can lead to significant impairment of
ventilation Reversal Agents
Midazolam • Opioids ➔ Naloxone

• Rapid and predictable onset of action • Benzodiazepine ➔ Flumazenil
• Short recovery time
Preprocedural Evaluation PAIN MANAGEMENT

• History and physical examination are critical P
ain Management in Neonates
before clearing a child for sedation or
anesthesia Non-pharmacologic pain management
–– Ask about past medical history, previous • For minor procedures, e.g., heel stick, veni-
sedation or anesthesia puncture, subcutaneous injections:
–– Last solid and liquid oral intake –– Oral sucrose/glucose
–– Recent illness –– Breastfeeding
–– Current medications, allergies, or side –– Nonnutritive sucking
effects of medications –– Skin to skin contact “kangaroo care”
–– Family history –– Facilitated tuck (holding the arms and legs
–– Upper respiratory infection symptoms; his- in a flexed position)
tory of reactive airway disease –– Swaddling
–– Airway, cardiac, pulmonary, and neurolog- –– Limiting environmental stimuli, lateral
ical examination positioning, the use of supportive bedding,
and attention to behavioral clues
–– Minimize the frequency and number of
I ntraprocedural Monitoring:
procedures.
Monitoring during procedural sedation
Pharmacologic pain management
• Continuous oxygen saturation and heart rate
• Topical anesthetic for painful procedures,
monitoring
e.g., lumbar puncture
• Monitor vital signs and blood pressure every
–– Topical anesthetics can effectively reduce
15 min for conscious sedation and every
pain, e.g., lidocaine
5 min for deep sedation
–– Give sufficient length of time before the
• Monitor state of consciousness and response
procedure (usually 30 min for neonates)
to stimulation
• Acetaminophen
–– Administered orally postoperatively has been
Discharge Criteria After Sedation or shown to reduce morphine requirements.
Anesthesia –– Should not be used alone for severe pain.
–– Use during the later postoperative period.
• Vital signs should be within normal range of –– Use after minor procedures, e.g.,
age. circumcision.
• Child should be able to ambulate as appropri- • Morphine for postoperative pain
ate for age and without assistance.
• Child should be able to tolerate oral intake.
Pain Management in Older Children
Sedation for simple and short Pain scale assessment (Fig. 31.2)
procedures (Table 31.12)
Postoperative pain management
Table 31.12 Antihistamines with sedative effects Morphine IV
Medications Dose • Moderate-severe pain after surgeries
Diphenhydramine 1 mg/kg; maximum 50 mg/dose
• Use the lowest effective dose
(PO, IV, IM)
Hydroxyzine (PO) 2 mg/kg/day divided every 6–8 h; • Acute pain may counteract the respiratory
maximum 600 mg/24 h depression induced by morphine
PO per os, IV intravenous, IM intramuscular
944 O. I. Naga
Fig. 31.2 Pain scale

assessment, no pain, mild
pain, moderate and
severe pain
No pain Mild pain Moderate pain Severe pain
• Repeated doses every four to 6 h based on • Reserve opioids for moderate to severe pain,
additional pain assessment (see Fig. 31.2) e.g., after bone surgeries
• Using appropriate dosing of acetaminophen
after surgery may reduce the requirements for Codeine
morphine or opioids in general • No longer recommended in pediatrics
• Can cause severe nausea and vomiting
Ketorolac IV • 3% to 5% of population over metabolize,
• Nonsteroidal anti-inflammatory drug potentially leading to catastrophic overdose
• Not associated with common opioid side
effects, such as respiratory depression, nau-
sea, vomiting, urinary retention, or sedation PEARLS AND PITFALLS
• Attention must be paid to postoperative bleed-
ing after tonsillectomy • If planning to check the serum level of a drug,
measure the serum level after the steady-state
Acetaminophen (rectal) serum level is achieved, which is about five
• Provides good analgesic and morphine-spar- half-lives.
ing effects, even in neonates and infants, after • Red man syndrome is a common adverse
major surgery drug reaction of vancomycin; it is infusion
rate related. It is not an allergic reaction.
Post-operative pain management with conver- • Red man syndrome symptoms vary from mild
sion to oral agents flushing, urticaria, and pruritus to severe
• Ibuprofen manifestations, which include generalized
• Acetaminophen erythema, intense pruritus, and distributive
• Hydrocodone shock.
• Red man syndrome can be avoided by
Opioids as outpatient infusing the vancomycin over 60 min, and
• Because of side effects such as drowsiness symptoms can be ameliorated by discon-
and constipation, some surgeons avoid using tinuing or slowing the infusion, diphen-
opioids after surgeries, taking pain scale hydramine is not effective is treating these
assessment into consideration symptoms.
• In mild to moderate pain, may alternate ibu- • Trough level is measured before the next dose
profen and acetaminophen instead of a drug, and peak level is measured after the
• Appropriate dosing of acetaminophen and dose is administered.
ibuprofen may reduce postoperative opioid • Peak levels are not necessary for cases being
requirements treated with a course of antibiotics without a
• Substitute codeine with acetaminophen/ibu- positive culture.
profen or oxycodone
• Most cases of penicillin allergies are non- administration: a review. Children (Basel).
IgE-mediated; there is a low risk of allergic 2015;2(2):244–71.
reaction to first-generation cephalosporins in Chang WT. Pediatric sedation. Medscape [Internet].
penicillin-allergic patients and much lower Updated 8 May 2018. Medscape. New York:
risk for third-generation cephalosporins. WebMD. https://emedicine.medscape.com/
• Infants receiving acyclovir suppressive ther- article/804045-overview#a8. Accessed 26 Dec
apy after neonatal herpes simplex infection 2018.
should have CBC at 2 and 4 weeks after start- De Sutter AIM, van Driel ML, Kumar AA, Lesslar
ing treatment and then monthly to calculate O, Skrt A. Oral antihistamine- decongestant-
the absolute neutrophil count and monitor for analgesic combinations for the common cold.
the development of neutropenia. Cochrane Database Syst Rev. 2012;2:CD004976.
• Nonprescription (OTC) and prescription for Drugs.com [Internet]. Common side effects from
cough and cold medications are not recom- antibiotics, and allergies and reactions. n.d.
mended for treating common cold in children Updated 3 Mar 2017. Drugs.com. https://www.
younger than 6 years of age. drugs.com/article/antibiotic-sideeffects-aller-
• Most common side effects of ADHD medica- gies-reactions.html. Accessed 21 Oct 2018.
tions are loss of appetite, abdominal pain, and Ginsburg CM, McCracken GH Jr, Petruska
headaches; these symptoms may be lessened M, Olsen K. Effect of feeding on bioavail-
if the medication is taken with food. ability of griseofulvin in children. J Pediatr.
• Ketorolac used postoperatively is not associ- 1983;102(2):309–11.
ated with common opioid side effects such as Gupta AK, MacLeod MA, Foley KA, Gupta G,
respiratory depression, nausea, vomiting, uri- Friedlander SF. Fungal skin infections. Pediatr
nary retention, or sedation. Rev. 2017;38(1):8–22.
• Appropriate dosing of acetaminophen and Lowry JA, Leeder JS. Over-the-counter medica-
ibuprofen after surgery may reduce postop- tions: update on cough and cold preparations.
erative opioid requirements. Pediatr Rev. 2015;36(7):286–97. quiz 298
Myers AL, Gaedigk A, Dai H, James LP, Jones
BL, Neville KA. Defining risk factors for red
Suggested Reading man syndrome in children and adults. Pediatr
Infect Dis J. 2012;31(5):464–8.
Akdis AC, Sicherer SH. Allergy and the immu- Rakovchik EE, Fein DM. Nonsteroidal anti-
nologic basis of atopic disease. In: Kliegman inflammatory drug and salicylate poisoning.
RM, Stanton BF, St. Geme III JW, Schor NF, Pediatr Rev. 2016;37(1):48–50.
Behrman RE, editors. Nelson textbook of pedi- Sandritter TL, McLaughlin M, Artman M,
atrics. 20th ed. Philadelphia: Elsevier Saunders; Lowry J. The interplay between pharmacoki-
2016. p. 1074–7. netics and pharmacodynamics. Pediatr Rev.
American Academy of Pediatrics, Committee on 2017;38(5):195–206.
Fetus and Newborn, Canadian Paediatric Society, Tom-Revzon C. Drug interactions. Pediatr Rev.
Fetus and Newborn Committee. Prevention and 2006;27(8):315–7.
management of pain in the neonate. An update. Wagner J, Abdel-Rahman SM. Pediatric pharma-
Adv Neonatal Care. 2007;7(3):151–60. cokinetics. Pediatr Rev. 2013;34(6):258–69.
Barnes S, Yaster M, Kudchadkar SR. Pediatric seda- Weaver DJ Jr. Hypertension in children and ado-
tion management. Pediatr Rev. 2016;37(5):203–12. lescents. Pediatr Rev. 2017;38(8):369–82.
Batchelor HK. Influence of food on paediatric
gastrointestinal drug absorption following oral
Radiology Review
32
Wendy G. Kim and Michael George
C ARDIOTHORACIC RADIOLOGY and obscured vascular markings. Typically,

patients with this finding will demonstrate lower
Case 1 lung volumes, due to alveolar collapse, prior to
Preterm infant born at 32 weeks gestational age intubation.
presenting with respiratory distress
Imaging findings (Fig. 32.1): Frontal chest Diagnosis: Surfactant deficiency disease (respi-
radiograph demonstrates diffuse granular opacities ratory distress syndrome).
Fig. 32.1
W. G. Kim (*) · M. George

Department of Radiology, Boston Children’s Hospital, Harvard
Medical School, Boston, MA, USA
e-mail: Wendy.Kim@childrens.harvard.edu

948 W. G. Kim and M. George
Case 2 air dissecting into the interstitium (arrows).

8-day-old infant born prematurely with a history Subsequent radiograph (b) shows a large lucency
of surfactant deficiency developing respiratory (∗) surrounding the right lung with resultant con-
instability and decreased breath sounds on the tralateral mediastinal shift.
right
Imaging findings (Fig. 32.2): Frontal chest Diagnosis: Pulmonary interstitial emphysema
radiograph (a) demonstrates tubular and cystic and resultant tension pneumothorax.
lucencies throughout the right lung representing
a b
Fig. 32.2
32 Radiology Review 949
Case 3 Case 4
Post-term infant with history of prolonged delivery Newborn infant with respiratory distress and
and amniotic meconium staining presenting with absent breath sounds on the left
respiratory distress Imaging findings (Fig. 32.4): Frontal chest
Imaging findings (Fig. 32.3): Frontal chest radiograph demonstrates multiple tubular and
radiograph demonstrates coarse, ropy perihilar rounded lucencies in the left hemithorax with con-
opacities, and segmental areas of air trapping tralateral mediastinal shift. The left diaphragm is
(arrowheads). Lung volumes are large. indistinct. Note the nasogastric tube terminating
above the left hemidiaphragm (arrow).
Diagnosis: Meconium aspiration syndrome.
Diagnosis: Congenital diaphragmatic hernia
(Bochdalek hernia), which occurs most commonly
on the left. A right-sided hernia, or any hernia
including the liver, is associated with a worse
prognosis, often due to degree of ipsilateral lung
hypoplasia.
Fig. 32.3
Fig. 32.4
Case 5 Diagnosis: Congenital pulmonary airway malfor-

Newborn infant with prenatal diagnosis of chest mation, type II. The lack of systemic arterial sup-
mass ply distinguishes this lesion from a pulmonary
Imaging findings (Fig. 32.5): Frontal chest sequestration or hybrid lesion.
radiograph (a) shows an area of lucency in the
right lower lobe (arrow). Coronal chest CT (b)
demonstrates a predominantly right lower lobe
multicystic lesion.
a b
Fig. 32.5
Case 6 hyperinflation of the left upper lobe with attenua-

1-month-old infant presenting with respiratory tion of the pulmonary vasculature. There is medi-
distress astinal shift and compressive atelectasis of the
Imaging findings (Fig. 32.6): Frontal radio- dependent left lower lobe (arrows).
graph of the chest (a) shows asymmetric hyperlu-
cency of the left lung (∗) with mild rightward Diagnosis: Congenital lobar emphysema, which
mediastinal shift. Axial CT of the chest (b) shows most commonly involves the left upper lobe.
a b
Fig. 32.6
Case 7 grade via gastrostomy extending up only a short

Newborn infant with heart murmur and limb segment of the distal esophagus (arrowhead),
abnormalities presenting with difficulty feeding approximately 6 cm from the proximal esophageal
and inability to pass a nasogastric tube tube.
Imaging findings (Fig. 32.7): Frontal chest
radiograph (a) demonstrates a nasogastric tube ter- Diagnosis: Long gap esophageal atresia with tra-
minating in the upper mediastinum in the expected cheoesophageal fistula in the setting of VACTERL
location of the proximal esophagus (arrow). association (Vertebral defects, Anal atresia,
Intraoperative fluoroscopic image of the chest (b) Cardiac defects, Tracheo-Esophageal fistula, Renal
demonstrates enteric contrast administered retro- anomalies, and Limb abnormalities).
a b
Fig. 32.7
Case 8 Case 9
Newborn infant presenting with cyanosis, arrhyth- Newborn infant presenting with cyanosis and sys-
mia, and holosystolic murmur tolic murmur
Imaging findings (Fig. 32.8): Frontal chest Imaging findings (Fig. 32.9): Frontal chest
radiograph demonstrates a markedly enlarged car- radiograph demonstrates a “boot-shaped” heart
diac silhouette, often referred to as a “box shaped” with upturned cardiac apex due to right ventricular
due to asymmetric enlargement of the right heart. hypertrophy. Note the decreased pulmonary vas-
cular markings.
Diagnosis: Ebstein’s anomaly.
Diagnosis: Tetralogy of Fallot. The degree of pul-
monary oligemia reflects the severity of pulmo-
nary stenosis and subsequent right to left shunt
across the ventricular septal defect (VSD).
Fig. 32.8
Fig. 32.9
Case 10 loss of normal shouldering of the aryepiglottic

15-month-old male presenting with inspiratory folds (arrow). There is ballooning of the hypo-
stridor and barking cough pharynx (∗) on lateral view (b) due to air
Imaging findings (Fig. 32.10): Anteroposterior trapping.
(AP) radiograph of the neck (a) demonstrates
smooth tapering of the subglottic trachea, with Diagnosis: Croup (laryngotracheobronchitis).
a b
Fig. 32.10
Case 11 hyperinflation in the right lung (∗). The right lung

2-year-old female presenting with wheezing and does not collapse when placed in the right decubi-
found choking and coughing while playing with tus position and remains more lucent than the left
small toys lung.
Imaging findings (Fig. 32.11): Frontal supine
(a) and right lateral decubitus (b) radiographs of Diagnosis: Foreign body aspiration, most likely
the chest demonstrate asymmetric lucency and in the right mainstem bronchus.
a b
Fig. 32.11
Case 12 Diagnosis: Round pneumonia. This appearance

5-year-old male presenting with fever and cough can be seen in children under 8 years old due to
Imaging findings (Fig. 32.12): Frontal (a) and underdevelopment of pores of Kohn, or collateral
lateral (b) radiographs of the chest demonstrates a airways, which limits the spread of infection.
rounded airspace opacity in the right upper lobe
(arrows).
a b
Fig. 32.12
Case 13 ing the right hemidiaphragm. There are also opaci-

12-year-old female presenting with fever and ties in the right middle lobe, which obscure the
cough right heart border.
Imaging findings (Fig. 32.13): Frontal (a) and
lateral (b) radiographs of the chest demonstrate Diagnosis: Lobar pneumonia.
dense opacification of the right lower lobe, obscur-
a b
Fig. 32.13
Case 14 hilar opacity (arrow). Coronal CT (b) demon-

2-month-old female with 10 days of fever, with strates extensive mediastinal and hilar hypoattenu-
additional history revealing that the patient’s ating lymph nodes (arrowheads), in keeping with
grandmother was recently diagnosed with active necrotic lymphadenopathy.
tuberculosis
Imaging findings (Fig. 32.14): Frontal radio- Diagnosis: Active tuberculosis.
graph of the chest (a) demonstrates a rounded right
a b
Fig. 32.14
Case 15 maximum intensity projection (MIP) images dem-

15-year-old female on oral contraceptives present- onstrates multiple filling defects in the main and
ing with shortness of breath and pleuritic chest lobar pulmonary arterial branches bilaterally
pain (arrows).
Imaging findings (Fig. 32.15): CT angiogra-
phy of the chest with axial (a) and coronal (b) Diagnosis: Pulmonary thromboembolism.
a b
Fig. 32.15
Case 16 Case 17
16-year-old male with chronic cough, exercise Previously healthy 14-year-old female admitted to
intolerance, and frequent bulky, greasy stools the hospital with right lower lobe mycoplasma
Imaging findings (Fig. 32.16): Frontal radio- pneumonia, presenting with acute respiratory fail-
graph of the chest demonstrates hyperinflation of ure and clinical deterioration
the lungs, upper lobe predominant cystic bronchi- Imaging findings (Fig. 32.17): Frontal radio-
ectasis and bronchial wall thickening, apical pleu-
graph of the chest demonstrates diffuse coalescent
ral thickening, and small nodular opacities in theairspace opacities. The patient was intubated and
peripheral lungs. cannulated for veno-venous extracorporeal mem-
brane oxygenation. A small pleural effusion is
Diagnosis: Cystic fibrosis. The peripheral nodu- present on the right.
lar opacities typically reflect mucus plugging in
terminal bronchioles. Diagnosis: Acute respiratory distress syndrome
(ARDS).
Fig. 32.17
Fig. 32.16
Case 18 space (arrow). CT of the chest with contrast (c) dem-

16-year-old female presenting with several days of onstrates a heterogeneous, enhancing, lobular soft
malaise, chest discomfort, and loss of appetite tissue mass in the anterior mediastinum (∗). The mass
Imaging findings (Fig. 32.18): Frontal radiograph surrounds the mediastinal vessels without compress-
of the chest (a) demonstrates an abnormal and marking them.
edly widened mediastinal contour (arrows). Lateral
radiograph (b) localizes the abnormality to the ante- Diagnosis: Lymphoma.
rior mediastinum with loss of the retrosternal clear
a b
Fig. 32.18
GASTROINTESTINAL tureless bowel loops with intramural lucencies that

outline the bowel walls (arrows). Branching lucen-
RADIOLOGY cies over the liver are also noted, indicative of por-
Case 19 tal venous gas (arrowheads).
12-day-old infant with history of prematurity, pre-
Diagnosis: Pneumatosis intestinalis and portal
senting with abdominal distension
venous gas in the setting of necrotizing
Imaging findings (Fig. 32.19): Frontal supine enterocolitis.
(a) and cross table lateral (b) radiographs of the
abdomen demonstrate markedly distended, fea-
a b
Fig. 32.19
Case 20 lining the falciform ligament (arrow). A subse-

12-day-old infant born at 29 weeks gestational quent lateral decubitus radiograph (b) better
age presenting with abdominal distension and demonstrates the abnormal lucency which is now
hypotension seen in the antidependent abdomen adjacent to the
Imaging findings (Fig. 32.20): Frontal radio- liver (arrow).
graph of the abdomen (a) demonstrates abnormal
featureless appearing tubular bowel loops with a Diagnosis: Bowel perforation with
large vague lucency under the mid diaphragm out- pneumoperitoneum.
a b
Fig. 32.20
Case 21 Diagnosis: Meconium peritonitis, an incidental

1-year-old with abdominal pain finding indicating in utero bowel perforation and
Imaging findings (Fig. 32.21): Abdominal chemical peritonitis due to meconium.
radiograph demonstrates amorphous calcifications
(arrows) throughout the abdomen, many in a cur-
vilinear pattern, indicative of diffuse peritoneal
calcification.
Fig. 32.21
Case 22 hypoechoic muscular layer (solid line, > 3 mm).

3-week-old male presenting with projectile non- Note the fluid within the gastric antrum (arrow)
bilious, non-bloody emesis after feeding and lack of fluid in the duodenal bulb (arrowhead).
Imaging findings (Fig. 32.22): Transverse gray- No gastric contents were seen traversing the pylo-
scale ultrasound image of the epigastric region rus during the ultrasound exam.
demonstrates an abnormally elongated pyloric
channel (dashed line, > 14 mm) with thickened Diagnosis: Hypertrophic pyloric stenosis.
Fig. 32.22
Case 23 (arrows). An echogenic shadowing structure is

14-year-old male presenting with nausea, vomit- seen within the lumen of the appendix (∗), most in
ing, and periumbilical pain that migrated to the keeping with an appendicolith. Note the fluid and
right lower quadrant, with laboratory results echogenic fat surrounding the appendix, denoting
revealing a white blood cell count of 18,000 periappendiceal edema.
Imaging findings (Fig. 32.23): Focused right
lower quadrant ultrasound image demonstrates a Diagnosis: Acute appendicitis.
dilated (> 6 mm), tubular, and thickened appendix
Fig. 32.23
Case 24 Diagnosis: Malrotation with volvulus. The sec-

4-day-old male presenting with bilious emesis, ond and fourth segments of the duodenum should
abdominal distension, and feeding intolerance course retroperitoneally, and the duodenojejunal
Imaging findings (Fig. 32.24): Upper GI fluo- junction should be located at the same level of the
roscopic image of the abdomen during administra- duodenal bulb at approximately the L1 vertebral
tion of water-soluble enteric contrast demonstrates body on the left.
an abnormal corkscrew appearance of the proxi-
mal duodenum (arrow), which does not cross
midline.
Fig. 32.24
Case 25 sue filling defect within the mid transverse colon

2-year-old male with recent history of viral upper (arrow). Right lower quadrant ultrasound images
respiratory tract infection presenting with inter- (b, c) reveal a targetoid appearance of multiple
mittent bouts of severe abdominal pain and leth- alternating layers of bowel wall (arrows) and inter-
argy, with a palpable tubular mass in the upper posed mesenteric fat (∗), lymph nodes (∗), and
abdomen on examination fluid (∗).
Imaging findings (Fig. 32.25): Frontal abdomi-
nal radiograph (a) demonstrates a rounded soft tis- Diagnosis: Ileocolic intussusception.
a b
Fig. 32.25
Case 26 appearance of gaseous distension of the stomach

Newborn infant with trisomy 21 and history of (arrow) and duodenal bulb (arrowhead) with
polyhydramnios, presenting with bilious emesis absence of gas distally.
Imaging findings (Fig. 32.26): Radiograph of
the abdomen demonstrates a “double-bubble” Diagnosis: Duodenal atresia.
Fig. 32.26
Case 27 small caliber rectum with a transition point (arrow)

12-day-old infant with a diagnosis of 2q22.1 chro- at the rectosigmoid junction and dilatation of the
mosomal deletion with multiple congenital abnor- colon proximally. Normally, the rectum should be
malities, presenting with abdominal distension larger in caliber than the sigmoid colon (rectosig-
Imaging findings (Fig. 32.27): Abdominal moid ratio > 1).
radiograph (a) demonstrates gas distension of the
distal colon in the left hemiabdomen (arrow). Diagnosis: Hirschsprung disease.
Fluoroscopic contrast enema (b) demonstrates a
a b
Fig. 32.27
Case 28 matic cord. This structure demonstrates walls with

9-month-old male with a non-reducible left-sided alternating hypoechoic and hyperechoic layers
scrotal mass (arrow), indicative of gut signature. Note the small
Imaging findings (Fig. 32.28): Ultrasound adjacent hydrocele (arrowhead).
image of the left scrotum shows a structure extend-
ing from the inguinal canal adjacent to the sper- Diagnosis: Incarcerated inguinal hernia.
Fig. 32.28
Case 29 excretion into the small bowel. This was confirmed

2-week-old infant presenting with jaundice and on 24-h delayed imaging. No gallbladder was
conjugated hyperbilirubinemia identified.
Imaging findings (Fig. 32.29): Hepatobiliary
iminodiacetic acid scintigraphy (HIDA scan) Diagnosis: Biliary atresia.
shows uptake of radiotracer into the liver but no
Study name: Hepatobiliary
Anterior
60 %
0
0s 120 s 240 s 6 min 8 min 10 min 47
0
180 s
12 min 14 min 16 min 18 min 20 min 22 min All frames

%
50
24 min 26 min 28 min 30 min 32 min 34 min

0
59 min
Fig. 32.29
Case 30 intense focus of persistent abnormal tracer activity

10-year-old male presenting with lower gastroin- in the right lower quadrant (arrow). There is nor-
testinal bleeding mal uptake of tracer by the stomach.
Imaging findings (Fig. 32.30): Dynamic
abdominal scintigraphy with technetium-99m-la- Diagnosis: Functioning ectopic gastric mucosa
beled sodium pertechnetate demonstrates an (Meckel’s diverticulum).
%
Anterior
%
30
0
0s 60 s 120 s 180 s 240 s 5 min
30
0
29 min
Fig. 32.30
Case 31 object distinguish this from a simple coin. Ingested

2-year-old child presenting with throat pain foreign bodies in the esophagus are most com-
Imaging findings (Fig. 32.31): Frontal (a) and monly seen at the levels of the thoracic inlet, the
lateral (b) radiographs of the chest show a discoid aortic arch, and gastroesophageal junction.
metallic foreign body projecting over the upper
esophagus at the level of the aortic arch. The dou- Diagnosis: Button battery ingestion.
ble rim and slight step off along the edges of the
a b
Fig. 32.31
Case 32 with multiple air-fluid levels (arrows). There is

2-year-old with history of gastroschisis, presenting also a paucity of gas in the sigmoid colon and rec-
with abdominal pain and distention tum (∗).
Imaging findings (Fig. 32.32): Frontal and lat-
eral decubitus radiographs (a, b) of the abdomen Diagnosis: Small bowel obstruction.
demonstrate markedly dilated loops of small bowel
a b
Fig. 32.32
Case 33 ing of a long segment of the terminal ileum in the

12-year-old male with several weeks of intermit- right lower quadrant (arrows). Note also the
tent abdominal pain and diarrhea engorgement of the mesenteric vessels
Imaging findings (Fig. 32.33): MR enterogra- (arrowheads).
phy was performed. Gadolinium contrast-enhanced
coronal (a) and axial (b) T1-weighted, fat-satu- Diagnosis: Crohn’s disease with terminal ileitis.
rated MR images show enhancement and thicken-
a b
Fig. 32.33
Case 34 Imaging findings (Fig. 32.34): Coronal con-

3-year-old male presenting with abdominal pain trast-enhanced CT of the abdomen demonstrates a
and failure to thrive, with a palpable left upper large, round, and heterogeneously enhancing left
quadrant mass on examination and an abnormal suprarenal mass (∗). The left kidney is displaced
abdominal ultrasound which prompted further inferiorly (arrow).
evaluation with CT
Diagnosis: Neuroblastoma.
Fig. 32.34
GENITOURINARY RADIOLOGY Case 36

Newborn male infant with prenatal diagnosis of
Case 35 hydronephrosis
1-month-old infant presenting with discharge from Imaging findings (Fig. 32.36): Fluoroscopic
the umbilicus cyclic voiding cystourethrogram was performed.
Imaging findings (Fig. 32.35): Sagittal ultra- An oblique fluoroscopic image of the pelvis during
sound of the midline lower abdomen demonstrates voiding demonstrates abnormal dilatation and
a fluid-filled tract (arrows) extending from the elongation of the posterior urethra (arrow) proxi-
dome of the bladder to the umbilicus. Thickening mal to a thin radiolucent band of tissue (arrow-
of the soft tissues surrounding the umbilicus sug- head). Note also the trabecular appearance of the
gests inflammation. bladder (∗) due to muscular hypertrophy.
Diagnosis: Infected patent urachus. Diagnosis: Posterior urethral valve causing blad-
der outlet obstruction.
Fig. 32.35
Fig. 32.36
Case 37 blunting of the renal calyces in the right kidney

16-month-old male with febrile urinary tract and moderate distention of the renal pelvis and
infection calyces in the left kidney. The left ureter is also
Imaging finding (Fig. 32.37): Fluoroscopic dilated and tortuous.
voiding cystourethrography demonstrates abnor-
mal reflux of contrast into dilated renal collecting Diagnosis: Left grade IV and right grade III vesi-
systems bilaterally. There is mild distension and coureteral reflux.
Fig. 32.37
Case 38 of corticomedullary differentiation. Coronal

1-week-old infant with history of oligohydramnios, T2-weighted, fat-saturated MR image (b) shows
presenting with hypertension and bulging flanks the extent to which the kidneys occupy a majority
on examination of the abdomen.
Imaging findings (Fig. 32.38): Ultrasound
images of the left and right kidneys (a) demon- Diagnosis: Autosomal recessive polycystic kid-
strate markedly enlarged, echogenic kidneys with ney disease.
diffuse, innumerable small cystic lesions, and loss
a b
Fig. 32.38
Case 39 Case 40
3-year-old male with hemihypertrophy presenting Newborn infant with prenatal diagnosis of a left
with a palpable abdominal mass on examination adrenal mass
and an abnormal abdominal ultrasound which Imaging findings (Fig. 32.40): Ultrasound
prompted further evaluation with contrast- image (a) demonstrates a left suprarenal mass with
enhanced CT complex cystic features and multiple septations
Imaging findings (Fig. 32.39): Coronal con- (arrows). Multiple follow-up ultrasounds were
trast-enhanced CT of the abdomen demonstrates a obtained, which showed sequential decrease in
large, heterogeneous, rounded mass centered at the size. Follow-up imaging at 9 months of age (b)
superior pole of the left kidney (∗). Note the thin demonstrates complete resolution of the mass.
rim of renal parenchyma inferiorly (arrows)
stretching around the mass. Diagnosis: Adrenal hemorrhage.
Diagnosis: Wilms tumor.
Fig. 32.39
Fig. 32.40
Case 41 Case 42
15-year-old premenarchal female presenting with 15-year-old female presenting with acute-onset
recurrent pelvic pain right-sided pelvic pain and vomiting
Imaging findings (Fig. 32.41): Sagittal ultra- Imaging findings (Fig. 32.42): Transverse
sound image of the pelvis demonstrates a mark- ultrasound image of the pelvis (a) demonstrates an
edly distended endometrial (∗) and cervical asymmetrically enlarged and heterogeneously
(arrowhead) canal with homogeneous echogenic hypoechoic right ovary (arrow). Sagittal image of
material. the right ovary (b) shows peripheralized follicles
(arrows) and lack of color Doppler flow.
Diagnosis: Hematometrocolpos, in this case sec-
ondary to an imperforate hymen. Diagnosis: Right ovarian torsion.
Fig. 32.41
Fig. 32.42
Case 43 Case 44
12-year-old male presenting with right-sided tes- 19-month-old male presenting with hematuria
ticular pain for 4 h Imaging findings (Fig. 32.44): Transverse
Imaging findings (Fig. 32.43): Transverse ultrasound image of the bladder (a) demonstrates
ultrasound image of the scrotum (a) demonstrates an intraluminal, exophytic, lobular mass near the
asymmetrically diminished Doppler flow to the base of the bladder. There is color flow within this
right testis (∗). Sagittal ultrasound image of the mass on Doppler ultrasound (b), indicative of
right scrotum (b) demonstrates an abnormal con- vascularity.
tour of the spermatic cord and epididymal head
(arrow), indicative of a bell clapper deformity. Diagnosis: Rhabdomyosarcoma of the bladder.
There is a small associated hydrocele.
Diagnosis: Acute right testicular torsion.
a a
Fig. 32.43
Fig. 32.44
Case 45 T1-weighted MRI of the pelvis (b) demonstrates a

16-year-old sexually active female presenting with complex, rim enhancing tubular structure (arrow)
pelvic pain, fever, and cervical motion tenderness in the left hemipelvis, with extensive adjacent
Imaging findings (Fig. 32.45): Ultrasound enhancement.
image of the pelvis (a) demonstrates a complex
cystic mass in the left adnexal region (arrow). The Diagnosis: Tubo-ovarian abscess.
surrounding mesenteric fat is echogenic, sugges-
tive of adjacent inflammation. Note the normal
right ovary (∗). Post-gadolinium enhanced axial
a b
Fig. 32.45
MUSCULOSKELETAL oblique lucency through the tibial metaphysis

(arrows). On the lateral view, there is clear widen-
RADIOLOGY ing of the physis anteriorly (arrowhead). No
Case 46 epiphyseal component is appreciated.
12-year-old male with ankle pain after a basket-
Diagnosis: Salter Harris II fracture.
ball injury
Imaging findings (Fig. 32.46): Frontal and lat-
eral radiographs of the ankle demonstrate an
Fig. 32.46
Case 47 radial fracture extending to both the anterior and

15-month-old female presenting to the emergency posterior corners of the distal radius (arrowheads),
room with fussiness, with multiple bruises noted which has a “bucket-handle” appearance. This
on physical examination patient had similar appearing fractures in the tibia
Imaging findings (Fig. 32.47): Frontal radio- as well. Towne view of the skull (c) in the same
graph (a) of the right wrist demonstrates triangular patient shows a left occipital fracture.
bone fragments along the lateral aspect of the dis-
tal radial metaphysis and medial aspect of the dis- Diagnosis: Non-accidental trauma with classic
tal ulnar metaphysis (arrows), in keeping with metaphyseal lesions and skull fracture.
corner fractures. Lateral radiograph (b) shows the
a b c
Fig. 32.47
Case 48 wing, femoral shafts, and distal tibial diaphysis

4-year-old female with a history of multiple bilaterally (arrows). The bones are diffusely
fractures demineralized with thinning of the cortex.
Imaging findings (Fig. 32.48): Frontal radio- Numerous growth arrest lines are present (∗).
graph of the hips and lower extremities demon-
strates numerous healed fractures of the right iliac Diagnosis: Osteogenesis imperfecta.
Fig. 32.48
Case 49 knee demonstrates loss of normal fatty signal in

17-month-old female presenting to the emergency the same region (arrow). This is accompanied by
room with fevers and right knee warmth high signal on the T2-weighted MRI (c), indicative
Imaging findings (Fig. 32.49): Frontal radio- of marrow edema (arrow). Additional edema is
graph of the right knee (a) demonstrates a subtle noted in the overlying soft tissues and medial
lucency in the medial distal femoral metaphysis epiphysis (arrowheads).
(arrow). T1 weighted coronal MRI (b) of the right
Diagnosis: Acute osteomyelitis.
a b c
Fig. 32.49
Case 50 ping, and expansion of the distal radial and ulnar

2-year-old male with history of chronic renal dis- metaphyses bilaterally (arrows).
ease presenting with weakening grip
Imaging findings (Fig. 32.50): Frontal radio- Diagnosis: Rickets.
graphs of the wrists demonstrates fraying, cup-
Fig. 32.50
Case 51 (arrowhead) and large soft tissue component (∗).

7-year-old male with worsening, gradual right No internal matrix is appreciable. Axial, contrast-
thigh pain enhanced MRI (b) demonstrates a large surround-
Imaging findings (Fig. 32.51): Frontal radio- ing soft tissue mass with robust enhancement
graph of the right thigh (a) demonstrates a perme- (arrows).
ative, moth-eaten diaphyseal bone lesion (arrow)
with poorly defined margins, aggressive appearing Diagnosis: Ewing sarcoma.
periosteal reaction along the lateral cortex
a b
Fig. 32.51
Case 52 osteal reaction along the posteromedial metaphy-

8-year-old male with worsening right knee pain sis of the distal femur (arrow), and the periosteum
and no reported trauma has been lifted from the bone (Codman’s triangle,
Imaging findings (Fig. 32.52): Frontal and lat- arrowhead). Dense, amorphous calcific matrix is
eral radiographs of the distal left femur demon- present (∗) in the lesion.
strate an aggressive, permeative lesion with a wide
zone of transition between normal and abnormal Diagnosis: Osteosarcoma.
marrow. There is an aggressive, hair-on-end peri-
Fig. 32.52
Case 53 the distal femur. The lesion is oriented away from

11-year-old female with painless, firm, palpable the joint space and is in continuity with the bone.
lump of the left lower thigh There is no soft tissue component or periosteal
Imaging findings (Fig. 32.53): Frontal radio- reaction.
graph of the left knee demonstrates a protuberant
bone lesion arising from the medial metaphysis of Diagnosis: Osteochondroma.
Fig. 32.53
Case 54 No soft tissue component or periosteal reaction is

17-year-old male with worsening left ankle pain present. Sagittal, fluid sensitive MRI (b) of the dis-
and no antecedent trauma tal left fibula demonstrates numerous fluid–fluid
Imaging findings (Fig. 32.54): Frontal radio- levels within the lesion (arrow).
graph (a) of the left ankle demonstrates an expans-
ile, lucent lesion of the distal fibula (∗). There is a Diagnosis: Aneurysmal bone cyst.
narrow zone of transition proximally (arrowhead).
a b
Fig. 32.54
Case 55 the pelvis narrows sharply (∗). Frontal radiograph

4-year-old female with short stature of the hand (b) demonstrates short, broad metacar-
Imaging findings (Fig. 32.55): Frontal radio- pals with irregular metaphyses (arrow) and splay-
graph of the abdomen and pelvis (a) demonstrates ing of the digits.
narrowing rather than widening of the interpedun-
cular distances of the lower lumbar spine (arrow- Diagnosis: Achondroplasia.
heads). There iliac wings are broad (arrow) and
a b
Fig. 32.55
Case 56 Case 57
8-year-old male with fall on an outstretched hand 11-day-old infant with torticollis to the left
Imaging findings (Fig. 32.56): Lateral radio- Imaging findings (Fig. 32.57): High frequency
graph of the elbow demonstrates linear lucency gray-scale ultrasound of the right and left neck
through the anterior cortex of the distal humerus demonstrates asymmetric enlargement of the right
(arrow). The posterior fat pad is displaced from sternocleidomastoid muscle (∗).
the olecranon fossa (arrowhead), indicative of
joint effusion. Diagnosis: Fibromatosis colli.
Diagnosis: Supracondylar fracture.
Fig. 32.56
Fig. 32.57
Case 58 Case 59
9-year-old male with a fall on an outstretched 16-year-old male who complains of right hip pain
hand after sustaining an injury while playing hockey
Imaging findings (Fig. 32.58): Frontal radio- and is unable to flex the right hip on examination
graph of the elbow demonstrates abnormal medial Imaging findings (Fig. 32.59): Frontal radio-
and inferior positioning of the medial epicondyle graph of the pelvis demonstrates a small fragment
(arrow). There is subcutaneous edema over the adjacent to the right anterior superior iliac spine
medial aspect of the elbow (∗). The lateral epicon- (arrow).
dyle (arrowhead) is also abnormally laterally
positioned. Diagnosis: Apophyseal avulsion fracture of the
right anterior superior iliac spine, at the attach-
Diagnosis: Avulsion of the medial and lateral epi- ment of the sartorius tendon.
condyles of the elbow.
Fig. 32.59
Fig. 32.58
NEURORADIOLOGY (∗) predominantly within the right lateral ventri-

cle. There is also abnormal echogenicity of the
Case 60 right frontal periventricular white matter (arrow),
1-day-old infant born at 25 weeks gestational age indicative of parenchymal hemorrhage with evolv-
presenting with seizures and drop in hematocrit ing leukomalacia. Notice also the diffusely echo-
level genic ependymal lining, suggestive of chemical
Imaging findings (Fig. 32.60): Anterior fonta- ventriculitis.
nel approach coronal gray-scale ultrasound image
of the brain demonstrates enlarged lateral and third Diagnosis: Grade IV intraventricular
ventricles, with large volume echogenic material hemorrhage.
Fig. 32.60
Case 61 MRI of the spine (b) better demonstrates a soft tis-

Newborn infant with a sacral dimple on exam sue mass with fat signal (arrow) between the low-
Imaging findings (Fig. 32.61): Sagittal ultra- lying conus and the terminus of the thecal sac.
sound image of the spine (a) demonstrates a low-
lying conus medullaris terminating at the sacral Diagnosis: Tethered cord with a terminal lipoma.
level with thickened and echogenic appearance of
the filum terminale (arrow). Sagittal T2-weighted
a b
Spine SAG
Fig. 32.61
Case 62 rowing of the nasopharynx (arrow). This prompted

5-year-old male presenting with neck pain, stiff- a contrast-enhanced CT of the neck (b), which
ness, fever, and difficulty swallowing shows a peripherally enhancing, low density col-
Imaging findings (Fig. 32.62): Lateral radio- lection extending along the retropharyngeal soft
graph of the neck (a) demonstrates abnormal tissues (∗).
thickening of the retropharyngeal soft tissues (∗),
larger than the width of a cervical vertebral body. Diagnosis: Retropharyngeal abscess.
There is also adenoid enlargement causing nar-
a b
Fig. 32.62
Case 63 foramina along the nerve roots bilaterally, larger

5-year-old male with multiple cutaneous neurofi- on the left side.
bromas and café-au-lait spots presenting with arm
weakness and palpable left neck mass Diagnosis: Bilateral cervical and brachial plexus
Imaging findings (Fig. 32.63): Coronal MRI of plexiform neurofibromas in the setting of neurofi-
the cervical spine demonstrates multiple lobular bromatosis type 1.
hyperintense lesions extending from the neural
Fig. 32.63
Case 64 demonstrates associated parenchymal volume

9-month-old male with facial port wine stain and loss. Axial susceptibility weighted MRI (c) better
intractable seizures shows the distribution of predominantly subcorti-
Imaging findings (Fig. 32.64): Axial CT of the cal mineralization.
brain (a) shows cortical and subcortical mineral-
ization in the bilateral posterior parietal and occip- Diagnosis: Sturge–Weber syndrome.
ital lobes (arrows). Axial T2-weighted MRI (b)
a b c
Fig. 32.64
Case 65 ules along the bilateral lateral ventricles (arrows).

5-day-old infant with prenatal history of multiple There are also multiple areas of cortical and sub-
cardiac and brain lesions cortical thickening and hyperintensity, indicative
Imaging findings (Fig. 32.65): Axial of cortical tubers (∗).
T1-weighted inversion recovery MRI of the brain
shows multiple hyperintense subependymal nod- Diagnosis: Tuberous sclerosis complex.
Fig. 32.65
Case 66 esis of the corpus callosum, a Z-shaped configura-

Newborn infant with congenital hydrocephalus tion of the brainstem, and inferior vermian
and macrocephaly hypoplasia.
Imaging findings (Fig. 32.66): Axial and sagit-
tal MRI of the brain (a, b) demonstrates severe Diagnosis: Non-communicated hydrocephalus
hydrocephalus with marked dilatation of the lat- due to aqueductal stenosis, in the setting of Walker–
eral and third ventricles (∗). The cerebral aqueduct Warburg syndrome.
is not patent (arrow). Note is also made of dysgen-
a b
Fig. 32.66
Case 67 low-attenuation in the deep gray nuclei (arrows).

15-year-old male who sustained an asphyxiation/ Axial diffusion-weighted MRI of the brain (c)
strangulation event and subsequent cardiac arrest demonstrates symmetrically decreased diffusivity
Imaging findings (Fig. 32.67): Axial and sagit- involving the cortex, caudate, basal ganglia, and
tal CT of the brain (a, b) demonstrates profound thalami, indicating diffuse ischemic change.
cerebral and cerebellar swelling with uncal, trans-
tentorial, and tonsillar herniation. Note the loss of Diagnosis: Global hypoxic ischemic injury.
gray white matter differentiation, loss of extra-
axial spaces, and also the more pronounced focal
a c
Fig. 32.67
Case 68 There is a subjacent biconvex hyperdense collec-

5-year-old child who fell off his bike and hit his tion (∗) causing mild mass effect on the brain with
head slight midline shift toward the left.
Imaging findings (Fig. 32.68): Axial CT of the
brain in bone (a) and soft tissue (b) windows dem- Diagnosis: Skull fracture with an epidural
onstrate a non-displaced right parietal bone frac- hematoma.
ture (arrow) with an overlying scalp hematoma.
a b
Fig. 32.68
Case 69 obstructive supratentorial hydrocephalus with

4-year-old female presenting with several weeks of transependymal edema (∗). Post-contrast axial
headaches and gait instability MRI (b) shows the cystic and solid components of
Imaging findings (Fig. 32.69): Axial CT of the the tumor in the posterior fossa.
brain (a) demonstrates a large mass lesion centered
within the left cerebellar hemisphere and crossing Diagnosis: Juvenile pilocytic astrocytoma.
the midline (arrows). There is resultant acute
a b
Fig. 32.69
Case 70 Case 71
17-year-old male presenting with headache and 1-day-old infant born via spontaneous vaginal
bitemporal visual field defect delivery presenting with apneic episodes
Imaging findings (Fig. 32.70): Sagittal con- Imaging findings (Fig. 32.71): Axial diffusion-
trast-enhanced MRI of the brain demonstrates a weighted MRI of the brain shows geographic diffu-
mildly enhancing, solid, sellar mass (∗) expanding sion restriction of the entire left middle cerebral
the sella (arrow) and extending into the suprasellar artery (MCA) territory, including the thalamus, len-
cistern, exerting mass effect upon the optic tiform nucleus, and internal capsule.
chiasm.
Diagnosis: Acute left MCA territory infarction.
Diagnosis: Pituitary adenoma.
Fig. 32.70
Fig. 32.71
Case 72 There are multiple feeding vessels from the peri-

Newborn infant presenting with high output con- callosal and anterior choroidal arteries (arrow-
gestive heart failure and cranial bruit head). Note the yin-yang appearance of turbulent
Imaging findings (Fig. 32.72): Sagittal ultra- vascular flow on color Doppler ultrasound
sound images (a) and post-contrast sagittal MRI imaging.
(b) of the brain demonstrate aneurysmal dilatation
of the median prosencephalic vein (arrows), which Diagnosis: Vein of Galen malformation.
drains into enlarged dural venous sinuses (∗).
a b
Fig. 32.72
Case 73 Case 74
14-year-old female presenting with headache and 2-month-old female with a history of birth trauma
2 months of lower extremity paresthesia and acute- presenting with a hard palpable lump on the head
onset bilateral upper extremity paresthesia and Imaging findings (Fig. 32.74): Radiograph of
facial numbness the skull demonstrates fusiform elevation of the
Imaging findings (Fig. 32.73): Axial T2 fluid- left parietal subperiosteum with a thin rim of calci-
suppressed MRI of the brain demonstrates numer- fication (arrow).
ous ovoid T2 hyperintense lesions within the
juxtacortical and periventricular white matter of Diagnosis: Left parietal calcified
the supratentorial brain, particularly along the cal- cephalohematoma.
losal-septal junction. Additional lesions were pres-
ent in the posterior fossa, upper cervical cord, and
upper thoracic cord.
Diagnosis: Multiple sclerosis.
Fig. 32.74
Fig. 32.73
Case 75 and asymmetric thickening of the medial rectus

15-year-old male presenting with progressive right and superior oblique muscles (arrowheads). There
eye pain, swelling, and fever is proptosis of the right orbit (white arrow).
Imaging findings (Fig. 32.75): Axial (a) and
coronal (b) contrast-enhanced CT of the orbits Diagnosis: Postseptal orbital cellulitis compli-
demonstrates diffuse sinonasal opacification on cated by a subperiosteal abscess and myositis of
the right with a medial right orbital subperiosteal the medial rectus and superior oblique muscles.
abscess (∗), intraconal fat stranding (gray arrow),
a b
Fig. 32.75
Case 76 osseous erosion of the lateral mastoid cortex (white

7-year-old male with recurrent ear infections, pre- arrow). Axial post-contrast MRI (b) demonstrates
senting with left ear pain, posterior auricular a subperiosteal abscess in the left postauricular
swelling, and fluctuance region, with intracranial extension (gray arrow).
Imaging findings (Fig. 32.76): Axial CT of the
temporal bones (a) demonstrates opacification and Diagnosis: Coalescent mastoiditis complicated
coalescence of the left mastoid air cells. There is by intracranial and subperiosteal abscesses.
a b
Fig. 32.76
Case 77 Case 78
12-year-old patient with a midline anterior neck 9-year-old male presenting with growth arrest and
mass that moves with swallowing and tongue pro- worsening vision
trusion, with an ultrasound initially performed, Imaging findings (Fig. 32.78): Sagittal post-
prompting further evaluation with CT contrast MRI of the brain demonstrates a heteroge-
Imaging findings (Fig. 32.77): Axial (a) and neously enhancing, suprasellar mass (∗) centered
sagittal (b) contrast-enhanced CT of the neck dem- within the pituitary fossa and that extends into the
onstrates a cystic structure along the anterior mid- suprasellar cistern. Punctate areas of hypointensity
line infrahyoid neck (arrows), embedded within within the mass are indicative of calcifications.
the strap muscles. There is a thin enhancing wall
and no adjacent fat stranding to indicate active Diagnosis: Craniopharyngioma.
inflammation.
Diagnosis: Thyroglossal duct cyst.
Fig. 32.78
Fig. 32.77
Case 79 ture closure of the sagittal suture (arrow) with

10-month-old male with abnormal head shape, associated dolichocephaly.
worsening over several months
Imaging findings (Fig. 32.79): Surface ren- Diagnosis: Isolated sagittal craniosynostosis.
dered CT images of the skull demonstrate prema-
Fig. 32.79
Case 80 convexities and within the interhemispheric fissure

2-month-old male presenting after fall and change (arrows). Surface-rendered CT of the skull (b)
in mental status demonstrates a depressed right parietal skull frac-
Imaging findings (Fig. 32.80): Coronal CT of ture (∗).
the brain (a) demonstrates multiple thin hyper-
dense crescentic collections along the cerebral Diagnosis: Depressed skull fracture with trau-
matic subdural hemorrhages.
a b
Fig. 32.80
Suggested Reading Donnelly L. Fundamentals of pediatric imaging.

2nd ed. Philadelphia: Elsevier; 2016.
American College of Radiology. ACR Walters M, Robertson R. Pediatric radiology: The
Appropriateness Criteria®. n.d. Available at requisites. 4th ed. Philadelphia: Elsevier; 2017.
https://acsearch.acr.org/list. Accessed 11 Nov
2018.
Last-Minute Review
33
Osama I. Naga
LMR Section Page Main Chapter Page

Last-Minute Review (LMR) Sections Number Number
1 General Pediatrics 1016 1
2 Neonatology 1022 35
3 Adolescent Medicine 1027 81
4 Genetic Disorders 1032 103
5 Metabolic Disorders 1036 143
6 Mental and Behavioral Health 1039 167
7 Emergency Medicine 1044 197
8 Critical Care 1049 247
9 Infectious Diseases 1052 267
10 Hematology/Oncology 1060 345
11 Allergy and Immunology 1066 391
12 Endocrinology 1070 417
13 Orthopedics 1078 465
14 Sports Medicine 1083 507
15 Rheumatology 1085 525
16 Neurology 1087 551
17 Ophthalmology 1092 585
18 Ear, Nose, and Throat 1095 611
19 Cardiology 1099 643
20 Pulmonology 1104 691
21 Nutrition 1108 731
22 Gastroenterology 1110 757
23 Nephrology 1115 799
24 Fluids and Electrolytes 1119 825
25 Urology 1120 841
26 Dermatology 1122 855
27 Psychosocial Issues and Child Abuse 1125 887
28 Ethics 1128 903
29 Research and Statistics 1131 913
30 Patient Safety and Quality Improvement 1132 921
31 Pharmacology and Pain Management 1134 927
O. I. Naga (*)

1016 O. I. Naga
GENERAL PEDIATRICS
Osama I. Naga
Last-Minute Review—General Pediatrics Most Likely Answer

Which growth charts should be used for children World Health Organization (WHO) chart
between 0 and 2 years?
Which growth charts should be used for children CDC growth charts
> 2 years?
Birth weight of newborn usually regained at what 10–14 days
age?
Birth weight doubles at what age? 5–6 months
Birth weight triples at what age? 1 year
Normal weight gain after 2 years of age per year 2–3 kg/year approximately
Body mass index (BMI) should be used starting at 2 years
what age?
How is BMI calculated? Weight (kg)/[height (m)]2
What is the most common cause of failure to Inadequate caloric intake
thrive?
How much is birth length increased by 1 year of 50%
age?
Birth length doubles at what age? 3–4 years
What is the average growth length (growth 5 cm/year approximately
velocity) per year after 2 years of age (later
childhood)?
What is the approximate range of pubertal peak 7–12 cm/year in boys
growth velocities in boys and girls? 6–10.5 cm/year in girls
How much does the head circumference increase 1 cm/month
per month in the 1st year?
When does the head grow the fastest? First 60 days of life (0.5 cm/week)
Head circumference should be measured routinely 2 years
in each well visit until what age?
What is the risk for a premature infant with an Hydrocephalus
enlarged head circumference?
What is the study of choice for an infant who Head ultrasound (US)
presents with macrocephaly?
What is the study of choice for an infant who Brain MRI
presents with absolute microcephaly?
Child with enlarged head > 98th percentile, similar Benign familial macrocephaly
to the father, no symptoms and normal cognitive
function, head imaging study showed prominent
subarachnoid space especially in the frontal region
Anterior displacement of the occiput on one side Positional plagiocephaly
and the frontal region on the ipsilateral side and the
ear is more anterior on the side of occipital
flattening (parallelogram)
Anterior displacement of the occiput on one side Posterior plagiocephaly (craniosynostosis)
and frontal bossing on the contralateral side and
the ear is displaced more posteriorly (trapezoid)
33 Last-Minute Review 1017

The most common type of craniosynostosis Long narrow head (scaphocephaly), which is an
early closure of the sagittal sutures
A 6-month-old with progressive head enlargement Scaphocephaly (craniosynostosis)
and crossing percentiles from 25th percentile at
2 months to 98th percentile at 6 months well visits.
The head is elongated in the anterior–posterior
diameter and shortened in the biparietal diameter.
Ridging of the sagittal suture is palpable
What is the next best step in a child with suspected Refer to a pediatric neurosurgeon (imaging
craniosynostosis? studies are not required to make the diagnosis in
typical cases)
What is the only vaccine that can be given at birth? Hepatitis B
Infant born to HBsAg positive mom what should Hepatitis B and HepB immunoglobulin in the
be given? first 12 h
What is the maximum age you can give DTaP? DTaP is only for children younger than 7 years
old
Encephalopathy within 7 days of administration is DTaP
an absolute contraindication in which vaccine?
When can Tdap or Td be given? 7 years and older
Rotavirus, measles, mumps, rubella (MMR), oral Live attenuated virus vaccines
poliovirus vaccine (OPV), and varicella are
How are MMR, varicella, and inactivated polio Subcutaneously (IPV can be given either IM or
(IPV) given? SC)
Can you give MMR vaccine and perform a purified Yes
protein derivative (PPD) test at the same time?
If you give only MMR vaccine, how long should 4–6 weeks
you wait to do PPD test?
Which vaccines are contraindicated to be given to Live vaccines, e.g., MMR, varicella, and
immunocompromised children? rotavirus
Anaphylaxis reaction to neomycin or gelatin is an MMR
absolute contraindication to which vaccine?
The child who received MMR vaccine 2 weeks ago Rubella
is now having pain in the hip joints. Which
component of the vaccine is responsible for this
reaction?
When does Haemophilus influenzae type b 5 years or older
vaccination not need to be given to healthy
children?
When does pneumococcal (PCV13) vaccination 5 years or older
not need to be given to healthy children?
For which conditions can you give Haemophilus One dose for unimmunized persons with
influenzae type b vaccination at 5 years of age or functional or anatomical asplenia and HIV
older? infection.
3 doses after hematopoietic stem cell transplant
(HSCT) regardless of the history of HIB
immunization
1018 O. I. Naga

Which pneumococcal vaccines should be given to PCV13, and PPSV23 (PPSV23 is given at least
high-risk children 2 years and older, e.g., HIV, 8 weeks after any prior PCV13)
sickle cell disease, asplenia, cochlear implant?
An 11-year-old female is here for HPV 2 doses 6–12 months apart
vaccination; how many doses are recommended?
A 15-year-old female is here for HPV vaccination; 3 doses 0, 1–2 months, and 6 months are
how many doses are recommended? recommended
Children younger than 9 years of age, never been 2 doses 1 month apart
vaccinated for influenza before; how many doses
should they receive during the first instance of
influenza vaccination?
Child has a severe egg allergy (anaphylaxis). Can Yes
he or she receive the MMR vaccine?
Child is allergic to eggs (only hives). Can he or she Yes
receive the influenza vaccine today?
Child has a severe egg allergy (anaphylaxis). Can Yes. Under the supervision of a health care
he or she receive the influenza vaccine? provider who can recognize and manage severe
allergic conditions
Child with a previous severe allergic reaction No
(anaphylaxis) to the flu vaccine. Can he or she
receive the influenza vaccine?
A 4-year-old boy has 104 °F fever and ear Yes
infection; can he be vaccinated today?
An unimmunized 4-month-old child came for No
catch-up vaccination. Can he or she receive the
rotavirus vaccine?
A 9-month-old boy came for catch-up vaccination, No
and he had only one dose of rotavirus vaccine at
2 months well visit. Can he receive the rotavirus
vaccine?
If a household member is immunocompromised, No
e.g., HIV, leukemia, or severe combined
immunodeficiency (SCID), can you give the
4-month-old who is living in the same house oral
poliovirus vaccine (OPV)
A 2-month-old child with complement component Routine 2 months vaccines plus meningococcal
deficiency. What are the vaccines that should be vaccine
given at the 2-months well visit?
A mother declined vaccination of her child. What Explore any misconceptions about the safety and
is the next best step? efficacy of vaccines
Visual acuity for a newborn is 20/400
At what age is a social smile seen? 1–2 months
An infant is able to track an object to 180° 2 months
Moro reflex disappears by what age? 3–6 months
An infant is able to roll from front to back and has 4 months
no head lag

An infant is able to roll from back to front, 6 months
supports weight with legs and bounces, able to
transfer objects from hand to hand, knows familiar
faces, knows own name, and begins to have
separation anxiety
An infant should be able to sit without support 7 months
An infant pulls to stand, says “mama/dada” 9 months
nonspecifically, and imitates sounds
An infant is able to stand and take steps, says 12 months
“mama/dada” specifically, has a mature pincer
grasp
Child is able to say 3–5 words, turns pages of a 15 months
book, builds a tower of 3 blocks
Child is able to say 10–25 words, throws a ball 18 months
overhand, builds 4 blocks towers, uses a spoon,
and knows 3 body parts
At what age are most toddlers able to use a cup 15–18 months
well?
Child says 50 words, 2-word sentences, throws 24 months
overhand, goes upstairs both feet on each step,
engages in parallel play
Child copies a circle, three-word sentences, 36 months (3 years)
alternates feet on stairs, knows 2 colors, 75%
intelligible speech
Child copies a square, 5-word sentences, identifies 48 months (4 years)
gender, knows 5 colors, 100% intelligible speech
Child copies a triangle, uses scissors, and can 60 months (5 years)
count to ten
At what age are most children able to copy a 6–7 years
diamond?
Inability to hold the head steady is a red flag for 4 months
abnormal motor development at what age?
Inability to sit alone and lack of rolling are a red 9 months
flag for abnormal motor development at what age?
Inability to walk independently is a red flag for 18 months
abnormal motor development at what age?
A 1-year-old boy is unable to stand or crawl, Motor, cognitive, and language delay
unable to point and is not speaking a single word
An 18-month-old with only 3 words, lack of joint Screen for autism spectrum disorder and
attention, not sharing the interest in an object developmental delay with 2 separate tools, e.g.,
M-CHAT and ASQ
A 2-year-old uses only 5 words. What is the best Hearing test
test to order?
The American Academy of Pediatrics (AAP) All infants with significant congenital hearing
recommends that universal hearing screening of all loss should be identified by 3 months of age, and
infants occur by what age? necessary intervention initiated by 6 months of
age
1020 O. I. Naga

AAP recommends universal screening for anemia 1 year of age
with determination of Hb concentration at what
age?
AAP recommends lead screening at what age? All Medicaid-eligible children and those whose
families receive any governmental assistance
must be screened at ages 1 and 2 years
What is the non-hematologic consequence of iron Neurocognitive changes
deficiency anemia?
AAP recommends autism screening at what age? 18 months and 24 months
AAP recommends discussing tobacco, alcohol, or 11 years
drug use with children at what age?
The US Preventive Services Task Force (USPSTF) Once between 15 and 18 years (younger if
recommended age to begin screening all increased risk, e.g., male-to-male sexual contact)
adolescents for HIV
Screening for depression should be done annually Starting at 12 years
starting at what age?
Screening for dyslipidemia should be done at what Between 9 and 11 years and again between 17
ages? and 21 years, or if there are risk factors (obesity,
diabetes, etc.)
A 7-year-old boy has a parent with total cholesterol Order fasting lipid profile, then repeat after
of 300 mg/dL. What is the next best step? 2 weeks to 3 months
Infant is exclusively breastfed. At what age should First few days of life
you recommend daily vitamin D supplementation
(400 IU)?
Infant is feeding more than 1 liter of formula per No (1 liter of formula has 406 IU of vitamin D)
day in addition to breastfeeding; does he or she
need vitamin D supplementation?
Infant is exclusively breastfed. At what age should 4 months
you recommend daily iron (1 mg/kg/day)?
At what age should you recommend starting solid 4–6 months
foods in infants?
What is the reason for starting solid foods between May decrease the risk of allergy to that specific
4 and 6 months of age? food
A 4-week-old infant has been exclusively Continue breastfeeding
breastfeeding, and the mother is scheduled for
MRI with contrast
A 4-week-old infant has been exclusively Continue breastfeeding (can continue on the
breastfeeding, and the mother has mastitis other side if breast abscess or cellulitis with
direct contact with infant’s mouth)
A 4-week-old infant has been exclusively Discontinue breastfeeding until effective
breastfeeding, and the mother recently diagnosed maternal treatment for the initial 2 weeks or the
with active tuberculosis. No treatment yet infant is receiving isoniazid)
Newborn with a mother who is HIV positive Breastfeeding is contraindicated (except in
resource-limited settings)
What is the age when infants can drink cow’s 12 months
milk?

At what age can a child be given low-fat milk? > 2 years
AAP recommends the initial visit to the dentist at 12 months of age
what age?
What usually are the first teeth to erupt? Lower anterior incisors
What is the latest age for first tooth eruption? 18 months (after that, dental consult)
Child with white lines and spots at the bases of Referral to a dentist (sign of dental caries)
several teeth
A 5-year-old boy hit his head and knocked out his Reassurance (re-implantation of the primary
2 primary central incisors 5 min ago. What is the tooth may damage the developing permanent
next best step? tooth)
A 10-year-old boy hit his head and knocked out his Re-implant the teeth immediately (best
2 permanent central incisors 5 min ago. What is prognosis if avulsed tooth re-implanted within
the next best step? 15–30 min)
If a tooth has been knocked out, it should be placed Cold milk
back into its socket until the child can see the
dentist, should that prove impossible, what is the
best solution in which to keep it?
When should the knocked-out tooth be implanted? Immediate treatment is essential
At what temperature should you set the water 120 °F or less
heater at home?
Child with a capillary lead level of > 5 μg/ Obtain venous sample
dL. What is the next best step?
What is the safe blood lead level (BLL)? There is no safe BLL, and any detectable lead
level must be managed
Children should be secured with a rear-facing seat? Birth to 2–4 years, as long as possible, or until
they reach the highest weight or height allowed
Children who have outgrown their rear-facing seat Forward-facing car seat until they reach the
should use? highest weight or height allowed or at least
5 years of age
Children who have outgrown their forward seating Booster seat
and are less than 57 in. (4 ft 9 in.) tall should use?
Children who have outgrown their booster (57 in., Seatbelt; if the seat belts fit properly when the
or 4 ft 9 in. tall) seat should use? lap belt lays across the upper thighs (not the
stomach), and the shoulder belt lays across the
chest (not the neck)
What is the recommended preventative measure to Enclosing the pool with a 4-ft fence
help prevent drowning?
What is the recommended measure to prevent Gun and bullets stored in locked and separate
accidental gun injuries? locations
AAP does not recommend the use of repellents for Children younger than 2 months
children at what age?
Treatment of a large local reaction after a mosquito Antihistamine, ice, and topical hydrocortisone
bite cream
What is the significant risk of sunburns? Increases risk of melanoma at all ages
What are the long-term complications of artificial Cataracts, skin aging, and cancer
ultraviolet rays (e.g., skin tanning)
1022 O. I. Naga
NEONATOLOGY
Mamta Fuloria
Last-Minute Review—Neonatology Most Likely Answer

Birth weight less than the 10th percentile Small for age (SGA)
Birth weight more than the 90th percentile Large for gestational age (LGA)
Birth weight less than 2500 g Low birth weight
Birth weight less than 1500 g Very low birth weight (VLBW)
Birth weight less than 1000 g Extremely low birth weight (ELBW)
Gestational age of screening for group B 35–37 weeks gestation
Streptococcus (GBS)
What is the drug of choice for GBS prophylaxis? Penicillin G
Mother currently GBS negative, but the previous Yes
infant had GBS disease. Is GBS prophylaxis
recommended?
Which group has the highest infant mortality rate in African American infants
the USA?
Most common cause of infant deaths in the USA Congenital malformations
What is the clinical significance of a single Associated fetal anomalies (20% or more)
umbilical artery?
The third trimester presents with Hemolysis, HELLP syndrome (complication of
Elevated Liver enzymes, Low Platelet count preeclampsia)
What is the definitive treatment for preeclampsia/ Delivery
HELLP syndrome?
The best course of action if fetal scalp pH < 7.20 Immediate delivery
Fetal heart rate > 160 beats/min Fetal tachycardia
Fetal heart rate < 110 beats/min Fetal bradycardia
Fetal head compression is often associated with Early deceleration (increased vagal tone)—
which type of deceleration? benign tracing
Compression of the umbilical cord is associated Variable decelerations
with which type of deceleration?
Fetal heart monitoring shows: Fetal heart dropped Late deceleration; associated with placental
during the peak uterine contraction and recovered insufficiency
after the contraction had ended; the time from the
onset of deceleration to the lowest point of
deceleration is 30 s
What are the common causes of late deceleration? Placental insufficiency for any reason
Uteroplacental insufficiency is associated with what Late deceleration—potentially ominous
type of deceleration?
The best course of action in cases of late Fetal pH measurement
deceleration
Newborn at 1 min: Heart rate is 90/min, weak 4
irregular respiration, grimace, some flexion, blue
body and limbs, APGAR score is:
Newborn infant is just delivered. The infant is Positive pressure ventilation (PPV) for 30 s,
apneic and has a heart rate < 100. What is the next then reassess
best step?

In the previous example, the infant’s heart rate is Chest compressions and PPV using 100%
< 60 bpm despite adequate ventilation for 30 s. oxygen
What is the next step?
In the previous example, the PPV is ineffective, and Intubation
chest compressions are being performed. What is
the next step?
In the previous example, the infant’s heart rate Intravenous administration of epinephrine
remains < 60 bpm despite adequate ventilation and
chest compressions. What is the next step?
Newborn infant with lanugo on the shoulders, 39 weeks—be familiar with Ballard scoring
creases on the entire foot, scant vernix, both
testicles in the inguinal canal with good rugae has
an approximate gestational age of?
Newborn with one side of the body pink and the Harlequin color change
other side pale, with a sharp line in-between, no
other symptoms
A neonate is born with severely thickened skin with Harlequin ichthyosis (autosomal recessive)
large, shiny plates of hyperkeratotic scales. Deep,
erythematous fissures separate the scales and
contraction abnormalities of the eyes (severe
ectropion), ears, mouth, and appendages
Newborn with a sharply demarcated ulcerated area Aplasia cutis congenita
of absent skin is?
What is the most common association with aplasia Benign isolated defect (less commonly
cutis congenita? associated with other physical anomalies or
malformation syndromes, e.g., trisomy 13)
Newborn infant with head swelling crossing the Caput succedaneum
suture lines; delivery was assisted with the use of a
vacuum?
Newborn infant with head swelling that does not Cephalohematoma
cross the suture lines?
A type of hemorrhage in which bleeding is Subgaleal hemorrhage
significant and often presents with swelling in the
posterior aspect of the head?
A 7-day-old, 28-week premature infant should be Intraventricular hemorrhage—with a head US
screened for which type of hemorrhage and with
which modality?
Maternal fever > 100.4 °F, fetal heart rate more Chorioamnionitis
than 160–180 beats/min, maternal tachycardia,
purulent foul-smelling amniotic fluid, maternal
leukocytosis, and uterine tenderness
A neonate is born to a mother with Obtain blood culture, complete blood cell
chorioamnionitis. The neonate is alert with good count, and start ampicillin and gentamicin
tone, no respiratory distress, and vital signs are
normal. What is the next best step?
1024 O. I. Naga

An infant develops cyanosis when feeding, which Bilateral choanal atresia
disappears when crying
Term infant 1 h after birth develops tachypnea, Transient tachypnea of the newborn (self-
hypoxia, grunting. Chest radiograph showed fluid limited, resolves spontaneously, and requires
in the fissures, flattening of the diaphragm, and supportive care)
prominent pulmonary vasculature
Newborn initially diagnosed with transient Consider another diagnosis
tachypnea of the newborn is requiring more oxygen
and is much worse after several days
A preterm newborn with tachypnea, grunting, nasal Respiratory distress syndrome
flaring, subcostal, and intercostal retractions. Chest
radiograph shows ground glass appearance. He
continues to require more oxygen
What is the best treatment in the previous case of Surfactant therapy followed by rapid extubation
respiratory distress syndrome? to nasal continuous positive airway pressure
(CPAP)
When is surfactant recommended to be used < 27 weeks gestation (some institutions give
prophylactically after resuscitation in extremely surfactant as rescue therapy)
premature neonates to protect the immature lungs?
The name of cells that produce lung surfactant Type 2 alveolar cells
An 8-week-old who was born at 27 weeks was Bronchopulmonary dysplasia
intubated for several weeks and now has chronic
hypoxemia, tachypnea, wheezing, along with
longstanding respiratory insufficiency. Chest
radiograph showed: Decreased lung volumes, areas
of atelectasis, hyperinflation, and pulmonary edema
Newborn infant with respiratory distress, bowel Diaphragmatic hernia
sounds in the chest, scaphoid abdomen. Bag-mask
PPV after delivery made the infant worse. Chest
radiograph shows: loops of bowel in the chest, a
mediastinal shift, a paucity of bowel gas in the
abdomen, and the presence of the tip of a
nasogastric tube in the thoracic stomach
What is the next best step in the newborn with the Intubate immediately after delivery, insert a
diaphragmatic hernia in the previous example? nasogastric tube to decompress the stomach
(avoid bag-mask ventilation)
Full-term infant presents with tachypnea, cyanosis Persistent pulmonary hypertension of the
only in the lower body, loud second heart sound. newborn
Chest radiograph shows clear lungs and decreased
vascular markings
A post-term newborn has respiratory distress. The Pneumothorax
amniotic fluid was stained with meconium, and the
point of maximal cardiac impulse is displaced
A common complication from excessive bagging Pneumothorax
during resuscitation?

Meconium-stained amniotic fluid is noted at PPV
delivery, and the infant is apneic. What is the next
best step?
Meconium ileus in a newborn Cystic fibrosis should be ruled out
A 2-week-old preterm infant born at 26 weeks Necrotizing enterocolitis
gestation started having more gastric residuals,
abdominal distension, blood in stool, abdominal
wall erythema. KUB shows pneumatosis intestinalis
and gas in the portal vein
Newborn with bilious vomiting, abdominal Volvulus should be ruled out
distension, and lethargy
Newborn with Down syndrome and bilious Duodenal atresia
vomiting. KUB shows double bubble sign
Differential diagnosis of white pupillary reflex Cataract, retinoblastoma
Anhidrosis, ptosis, miosis, and enophthalmos Horner syndrome
Newborn is not moving arm, and the arm is Erb’s palsy (C5–6)
internally rotated in waiter’s tip position
Newborn is not moving arm and hand, and the hand Klumpke paralysis (C8-T1)
is held in a claw-like position
A diagnostic test to assess associated findings with Chest radiograph can rule out phrenic nerve
brachial plexus palsies (BPP) injury and clavicular fracture
A 2-month-old infant has irritability and poor Infantile cortical hyperostosis (Caffey disease)
feeding, swelling, and bone lesions, elevated ESR,
and alkaline phosphatase levels. Radiographs show
layers of periosteal new bone formation, with
cortical thickening of the long bones, mandible, and
clavicle. Soft-tissue swelling is evident as well
A 5-day-old female with vaginal bleeding Reassurance (maternal hormone withdrawal)
A well-appearing term neonate with bluish Reassurance (peripheral cyanosis or
discoloration in hands and feet acrocyanosis is common and benign)
A neonate has new-onset seizure activity but Refer to the emergency department immediately
appears otherwise healthy
Large for gestational age, lethargy, tremors, Hypoglycemia
seizures, and cyanosis
Neonate with hypoglycemia diagnosed with Order plasma glucose level (most accurate);
glucose oxidase test strip; test strip glucose is feed infant immediately
30 mg/dL. What is the next best step?
Newborn with a micropenis that is less than 2.5 cm Endocrine evaluation
when stretched will require?
Newborn is very quiet, cries very little, and has Hypothyroidism
prolonged jaundice and umbilical hernia
Jaundice, hypocalcemia, and hypoglycemia are Polycythemia
usually associated with
What is the treatment of polycythemia? Hydration (IV fluids); if symptomatic or
significant polycythemia, will need an exchange
transfusion
1026 O. I. Naga

Is jaundice in the first 24 h physiologic? No
A condition specific for the infant of diabetic Small left colon syndrome
mother
An abdominal wall defect with uncovered Gastroschisis—not associated with genetic
abdominal contents noted right of the umbilicus is abnormalities
An abdominal wall defect covered with a Omphalocele—associated with genetic
membrane that is often associated with genetic abnormalities, e.g., trisomies 13, 18, and 21 and
syndromes is Beckwith–Wiedemann syndrome
Syndrome characterized by absent abdominal wall Prune belly syndrome
musculature as well as cryptorchidism is
A full-term newborn with missing right index, Amniotic band syndrome
middle, and ring fingers
Newborn with jitteriness, irritability, tremulousness, Cocaine abuse during pregnancy
limb defect, leukomalacia, and intracranial
hemorrhage
Very small for gestational age (SGA) infant, mother Cocaine
with multiple drug abuse during pregnancy,
including alcohol, cigarette smoking, cocaine,
marijuana. Which substance is most responsible for
SGA?
The most common effect of cigarette smoking Low birth weight
during pregnancy on newborn
Excessive exposure to hot water or hyperthermia Miscarriage, neural tube defect
during the first trimester of pregnancy increases the
risk of
A virus that can cause fetal hydrops Parvovirus B19
Newborn with microphthalmia, cataracts, blueberry Congenital rubella syndrome
muffin spots on the skin, hepatosplenomegaly, and
patent ductus arteriosus
Newborn with microcephaly, and periventricular Congenital cytomegalovirus infection
calcifications
Newborn with chorioretinitis, hydrocephalus, and Congenital toxoplasmosis
intracranial calcifications
Newborn with snuffles, continuous nasal secretions, Congenital syphilis
anemia, thrombocytopenia, hepatomegaly, and
periostitis
SGA newborn with short palpebral fissures, Fetal alcohol syndrome
epicanthal folds, micrognathia, smooth philtrum,
thin upper lip, and microcephaly
Lithium use during pregnancy is associated with Ebstein anomaly
Infant born to an opiate dependent mother presents Neonatal abstinence syndrome
with increased irritability, fussiness, poor feeding,
and sweating
Which maternal medication during pregnancy ACE inhibitors
results in a newborn with growth restriction, renal
dysgenesis, oligohydramnios, skull ossification
defects?

Which anticonvulsant is associated with fetal Phenytoin
hydantoin syndrome?
Valproic acid intake during pregnancy increases the Neural tube defect, cleft lip and palate,
risk of cardiovascular abnormalities, genitourinary
defects, developmental delay, endocrine
disorders, limb defects, and autism
The most common congenital defect associated Neural tube defect
with carbamazepine and valproic acid
Newborn with isolated congenital deafness Referral to a geneticist (genetic causes probably
account for the majority of cases in developed
countries)
A 3-day-old infant presents with bilateral hip US of the hips
clunks. What is the next best step?
An infant is delivered to HBsAg positive mother; Administer both hepatitis B vaccine and HBIG
what is the next step? within 12 h of birth
Critical congenital heart defects screening before Oxygen saturations should be > 95%, with no
discharge from the newborn nursery requirements more than a 3% difference between pre-ductal
in most states in the USA and post-ductal oxygen saturations
A mother who delivers a full-term newborn has 48 h after birth and follow-up in 2–3 days
negative routine maternal labs. The infant is born
by vaginal delivery and is stooling, voiding, feeding
well. Tc bilirubin is normal on the 25th percentile.
What is the recommended discharge time from
newborn nursery and follow-up-care?
What is the current recommendation for umbilical To keep it dry (use of isopropyl alcohol is no
cord care in infants born in developed countries? longer routine cord care)
ADOLESCENT MEDICINE
Hina J. Talib
Last-Minute Review—Adolescent Medicine Most Likely Answer

Adolescent male twin, whose female twin sibling Reassurance (growth spurt occurs at sexual
is taller than he is, is worried about his height maturity rating [SMR] II-III for girls, whereas at
SMR IV for boys)
The first sign of sexual development in boys Testicular enlargement
The first sign of sexual development in girls Breast development
Adolescent female is concerned about one breast Reassurance
being slightly larger than the other
A 15-year-old obese male with a sometimes Reassurance (benign gynecomastia)
painful breast that is larger than the other, with an
otherwise normal exam
Adolescent female is worried about painful masses Reassurance (fibrocystic changes)
noted in both breasts; the pain improves after her
menstrual cycle
1028 O. I. Naga

Adolescent female is concerned about a painless Reassurance (fibroadenoma)
rubbery mass located in the upper outer quadrant
that does not change in size throughout her cycle; a
well-circumscribed, smooth, mobile lesion
The most common cause of breast mass in Fibroadenoma
adolescent girls
The most common cause of mastitis in adolescent Staphylococcus aureus
girls
When does a girl usually get her first period? 2–3 years after breast development (12.5 years is
mean age)
The drug of choice for treatment of dysmenorrhea NSAID (cyclooxygenase inhibitors)
in adolescent females
The most common cause of secondary amenorrhea Pregnancy
in adolescents
The most common reason for hospitalization in Pregnancy
adolescents
Adolescent with amenorrhea, headaches, blurring Prolactinoma
of vision, galactorrhea
A concerned parent brings her 12-year-old female Reassurance (likely due to an immature
due to irregular periods; menarche was 6 months ago hypothalamic-pituitary-ovarian [HPO] axis)
Adolescent girl with irregular menstrual periods, Polycystic ovary syndrome (PCOS)
body mass index at the 98th percentile, acne,
acanthosis nigricans, hirsutism, male pattern
baldness/alopecia, elevated total and free
testosterone
A female adolescent presenting with abrupt onset Ovarian torsion
of severe, constant, unilateral pain located in the
pelvis, associated with recurrent nonbilious
vomiting; she has no fever, urinalysis is normal,
and pregnancy test is negative
What is the best way to encourage adolescents to Interview the adolescent alone and in a
disclose information to their pediatrician? confidential manner when discussing drugs,
contraception, STDs, suicidal ideation
A 16-year-old adolescent girl presents to your She can receive birth control pills without
clinic to discuss birth control options without parental consent at her current age
parental consent. She is sexually active. You live in
a state that allows minor consent for contraceptive
services
The 3 most common causes of death in adolescents Unintentional injuries, suicide, homicide
What are the consequences of e-cigarette use May lead to cigarette smoking as well as
among adolescents? nicotine addiction
What are the new alternative tobacco products E-cigarettes (most common), hookahs,
(ATPs) most commonly used by high school e-hookahs, and smokeless products such as snus
students? (moist powder tobacco)
What are the negative health impacts of ATPs? May be equal to or even worse than those
associated with cigarettes

What is the best approach to adolescents who are Provide an accurate and judgment-free education
smoking cigarettes or using ATPs? addressing the dangers of e-nicotine delivery
systems
The risk of accidental consumption by young Severe toxicity and death upon consumption
children, who may be drawn to brightly colored
and flavored e-cigarette liquids
What is the strongest predictor of serious problems Early age drug abuse (the younger the child, the
with substance use disorder? higher the risk)
Adolescent male presents to the ER with Opiates drug abuse, e.g., codeine
respiratory depression, euphoria, and pinpoint
pupils
Adolescent who lost his financial support presents Opiate withdrawal syndrome
with excessive yawning, tearing, dilated pupil,
insomnia, nausea, diarrhea, gooseflesh, and
cramping
Treatment of choice to treat opiate overdose Naloxone
Adolescent presents with conjunctival injection, Marijuana
gynecomastia, worsening school grades
Adolescent male with new-onset aggression, Synthetic marijuana intoxication
palpitations, confusion, and disorientation
Adolescent male presents with hypertension, Amphetamine intoxication
hyperthermia, decreased appetite and difficulty
sleeping
Adolescent presents with drowsiness, dry mouth, Lysergic acid diethylamide (LSD) toxicity
flushing, mydriasis, hallucination, delusions,
illusions, and body image distortion
Adolescent with recent schizophrenic thoughts, Phencyclidine (PCP) toxicity
depression, aggressive language, ataxia, and
nystagmus
Adolescent inhales toluene, xylene, presents with Myocardial infarction/cardiac arrhythmia
chest pain and loss of consciousness
What is the significant risk of inhalant abuse, Sudden sniffing death syndrome (cardiac arrest)
including those experimenting with inhalant abuse
for the first time?
Adolescent presents with euphoria, violent Gasoline inhalation
excitement, pulmonary hypertension, restrictive
lung defect, peripheral neuropathy,
rhabdomyolysis, and hematuria
Adolescent always absent from school presents Cocaine abuse
with chest pain and myocardial infarction
Adolescent with aggressive behavior, rage, anger, Anabolic steroids
acne, hirsutism, testicular atrophy, gynecomastia,
and libido alteration
Adolescent presents with euphoria, increased MDMA (ecstasy,
emotional energy, nausea, jaw clenching, teeth methylenedioxymethamphetamine)
grinding, blurred vision, anxiety, and psychosis
1030 O. I. Naga

The following sexually transmitted infections need HIV, chlamydia, gonorrhea, and syphilis
to be reported
Annual screening is indicated for sexually active Chlamydia trachomatis
females for which STD?
Adolescent male presents with severe dysuria, Gonococcal urethritis
profuse, purulent discharge
What is the best diagnostic test in cases of Urine nucleic acid amplification testing for
suspected gonorrhea or chlamydia in sexually gonorrhea and chlamydia
active adolescents?
Adolescent male presents with dysuria, purulent Disseminated gonorrhea
discharge, a petechial rash, as well as new-onset Treatment: IV ceftriaxone
knee pain
Adolescent male, sexually active, urethral Chlamydia trachomatis
discharge, Gram stain shows WBCs and no
organism
Adolescent with profuse, frothy, malodorous Trichomonas vaginalis infection
yellow-green vaginal discharge, vulvar irritation, Treatment: metronidazole or tinidazole
and strawberry cervix, vaginal pH < 4.5
Adolescent with a fishy odor, homogenous white Bacterial vaginosis
vaginal discharge, epithelial cells with a ragged Treatment: metronidazole (not considered STDs)
border on microscopic examination, vaginal pH
> 4.5
The most common cause of epididymitis in Chlamydia trachomatis
adolescents
Adolescent girl was sexually assaulted a few hours Empiric treatment for chlamydia, gonorrhea, and
ago Trichomonas
Adolescent female with lower abdominal pain, Pelvic inflammatory disease
fever, chills, dysuria, cervical motion tenderness,
and adnexal tenderness
A 17-year-old female is hospitalized for pelvic Clindamycin and gentamicin
inflammatory disease (PID) and has severe allergy
to cephalosporin. What is the best choice of
antibiotics?
A sexually active female presents with right upper Perihepatitis (Fitz–Hugh–Curtis syndrome)
abdominal pain, fever, and vaginal discharge
A sexually active adolescent with large, painless, Granuloma inguinale (caused by Klebsiella
and expanding suppurative ulcers that are beefy granulomatis)
and easily bleed on the coronal sulcus and
balanopreputial region
A sexually active adolescent with painful genital Chancroid (Haemophilus ducreyi)
ulcer and unilateral inguinal lymphadenopathy
A sexually active adolescent with a painless ulcer Chancre (primary syphilis)
on the dorsal penis, punched out, clean appearing,
sharp, firm, slightly elevated borders, and bilateral,
regional lymphadenopathy
A sexually active female presents to the clinic due Secondary syphilis
to a rash noted on the palms and soles, along with
flu-like symptoms, and malaise

A sexually active adolescent presents with several Neurosyphilis
days’ history of hearing loss, altered mental status,
and decreased sensation in both legs
A pregnant adolescent with secondary syphilis has Penicillin (desensitization)
anaphylaxis to penicillin. What is the drug of
choice?
Adolescent female, sexually active, presents with Herpes simplex infection
painful, itchy vesicular lesion on the vulvar area,
low-grade fever, cervical motion tenderness, thin,
white vaginal discharge
Two adolescents are ready to give birth; one has an Herpes simplex (genital warts are not an
active herpes genital lesion, and the other has indication of C-section)
genital wart. Which one should deliver by
C-section?
Adolescent boy discloses that on most days over Fluoxetine
the past month, he has been feeling irritable and
sad, has decreased pleasure in activities, weight
loss, lack of sleep, fatigue, and poor concentration.
What is the drug of choice?
A 15-year-old gymnast female presents with thin Anorexia nervosa
body habitus, bradycardia, lanugo hair,
amenorrhea. What do you suspect?
What are the most common electrolyte Hypophosphatemia, hypokalemia, and
abnormalities in refeeding syndrome? hypomagnesemia
Adolescent girl who has a BMI in the 93rd Bulimia nervosa
percentile with bilateral parotid enlargement,
erosions of the lingual surface of the teeth, loss of
enamel, dental caries?
SSRIs are more effective in treating which eating Bulimia nervosa
disorder?
Adolescent girl with migraine headaches wants Migraine with aura is an absolute
birth control pill. What condition do you need to contraindication to the use of combined oral
rule out? contraceptive pills
What is the most highly effective birth control Long acting reversible contraceptives, including
option available to an adolescent girl? intrauterine devices and subdermal implants
The percentile of BMI that is considered childhood ≥ 95th percentile for age and sex
obesity
The percentile of BMI that is considered Between the 85th and 95th percentiles for age
overweight in children and sex
Adolescent male with right breast enlargement that Reassurance (most cases of pubertal
is tender to touch, < 4 cm in size gynecomastia < 4 cm resolve within 3 years)
A 13-year-old girl with left-sided thoracic scoliosis Radiograph, and if Cobb angle ≥ 20°, refer to
on exam with a scoliometer showing 8°. What is orthopedics
your next step?
A 13-year-old adolescent presents for her third CDC now recommends that 11- to 12-year-old
HPV vaccination receive 2 doses of HPV vaccine instead of 3
doses (≥ 15 years of age require 3 doses)
1032 O. I. Naga
GENETIC DISORDERS
Golder N. Wilson
Last-Minute Review—Genetic Disorders Most Likely Answer

Both sexes are equally affected, both sexes Autosomal dominant (AD)
transmit to offspring, no skipped generation, every
child has a parent with disorder except new or
spontaneous mutation
Both sexes are equally affected, both sexes can Autosomal recessive (AR)
transmit a copy of mutated gene, and their risk to
have affected child is 25%, the disorder may be
seen in one or more sibling, not all generations are
affected
No male-to-male transmission, only females X-linked recessive
transmit the disease to their sons, daughters are
obligate carriers
Maternal transmission from egg to zygote; both Mitochondrial inheritance
males and females are affected
Hypotonia, upslanted palpebral fissures, epicanthal Down syndrome (trisomy 21)
folds, systolic murmur, single transverse creases in
hands, brachydactyly, broad space between the first
and second toe
Screening for hypothyroidism in cases of Down Newborn screening after birth, at 6 and
syndrome is at what age? 12 months, then annually if normal
Acute myeloid leukemia (AML) is a higher risk in < 1 year
the patient with Down syndrome at what age?
Acute lymphocytic leukemia (ALL) is a higher risk > 1 year
in the patient with Down syndrome at what age?
Newborn with Down syndrome with no murmur Echocardiography (50% of children with Down
on physical examination syndrome have a cardiac defect)
The most common cardiac defects associated with AV canal defects, ventricular septal defect, atrial
Down syndrome septal defect, and tetralogy of Fallot
The most common gastrointestinal defects Duodenal atresia, Hirschsprung disease
associated with Down syndrome
Newborn with clenched fist with overriding Trisomy 18 (Edward syndrome)
fingers, rocker bottom feet, small head, eyes, and
mouth with low-set malformed ears, micrognathia,
prenatal and postnatal growth deficiency,
hypotonia, and ventricular septal defect
Newborn with cleft lip, cleft palate, microcephaly, Trisomy 13 (Patau syndrome)
microphthalmia, cutis aplasia, and postaxial
polydactyly
A 5-year-old boy with intellectual disability, large Fragile X syndrome
hands and feet, long face with large ears, large
testicles, and hyperextensible joints

Newborn girl with microcephaly, ocular Wolf–Hirschhorn syndrome (4p-deletion)
hypertelorism, prominent glabella, frontal bossing
(Greek helmet face), beaked nose, hypotonia, and
seizures
Newborn with a cat-like cry, hypotonia, Cri du chat syndrome (5p-deletion)
microcephaly, moon face, widely-spaced eyes,
down-slanting palpebral fissures, high-arched
palate, and wide-flat nasal bridge
Newborn with microcephaly, atresia of the ear De Grouchy syndrome
canal, deep-set eyes, depressed mid-face, protruded
mandible, legs are flexed, externally rotated, and in
hyperabduction (frog-like position)
Newborn with profound hypotonia, small for Prader–Willi syndrome (PWS) (paternally
gestational age, feeding problems, failure to thrive, derived deletion 15q11–13)
bitemporal narrowing, thin upper lip, almond-
shaped eyes, hypogonadism, bilateral
cryptorchidism, and small penis
Child with hypotonia, jerky ataxic movement, fair Angelman syndrome (maternally derived
hair, large chin and mandible, inappropriate bouts deletion 15q11–13)
of laughter, and severe intellectual disability
Child with an intellectual disability, supravalvar Williams syndrome
aortic stenosis, hypercalcemia, friendly “cocktail
party” personality, and strabismus
The most common cause of hypercalcemia in a Idiopathic
child with Williams syndrome
Wilms tumor, Aniridia, Genitourinary WAGR syndrome
malformation, Retardation (intellectual disability),
long face, upward-slanting palpebral fissures,
ptosis, and a beaked nose, due to the absence of
PAX6 and WT1 (Wilms tumor) genes
Newborn with Coloboma, Congenital Heart CHARGE syndrome (gene defect CHD7 on
defects, choanal Atresia, growth and Retardation chromosome 8q)
(intellectual disability), GU anomalies
(hypogonadism), and Ear anomalies
Vertebral defects, Anal atresia, Cardiac defects, VACTERL/VATER association
Tracheoesophageal fistula, and/or Esophageal
atresia, Renal anomalies, and Limb defects
The most common association with VATER/ Congenital heart defects
VACTERL syndrome
Jaundice, bile duct paucity with cholestasis, Alagille syndrome (20p12)
peripheral pulmonary stenosis, butterfly vertebrae,
triangular face with a pointed chin, long nose with
broad mid-nose, and posterior embryotoxon
Cleft palate, absent thymus, hypocalcemia, DiGeorge syndrome (22q11.2)
tetralogy of Fallot, interrupted aortic arch,
recurrent infection, short stature, and behavioral
problem
1034 O. I. Naga

Cleft palate, micrognathia, glossoptosis, Pierre–Robin sequence
respiratory distress (airway obstruction caused by
backward displacement of the tongue base), and
feeding difficulties
Pierre–Robin sequence (cleft palate, glossoptosis, Stickler syndrome
and micrognathia or retrognathia); severe myopia
or other ocular abnormalities; sensorineural
hearing loss; or skeletal abnormalities including
hypermobility, scoliosis, or early arthritis
Newborn with a disruptive cleft on the face and Amniotic band sequence
amputated digits
Preauricular pits, preauricular tags, microtia, Branchio-oto-renal syndrome
hypoplastic cochlea, hearing loss, branchial fistula,
and renal dysplasia or aplasia
Newborn with underdeveloped mandibular and Treacher-Collins syndrome (mandibulofacial
zygomatic bones, microtia, stenosis of the external dysostosis type 1)
ear canal, down-slanting palpebral fissures,
coloboma, and conductive hearing loss
Short stature below third percentile, short length of Achondroplasia
the proximal segment of upper arms and legs
(rhizomelic shortening), trident hands, stenosis of
the foramen magnum, macrocephaly, flat nasal
bridge and mid-face
The most common cause of death in children Brain stem compression
younger than 4 years with achondroplasia
Child, with multiple bruises, blue sclera, recurrent Osteogenesis imperfecta (type I is the most
fractures, hyperextensible joints, and had delayed common)
closure of fontanelle
Adolescent, tall, the lens is dislocated upward, Marfan syndrome
high-arched palate, pectus carinatum, aortic
dilatation, and lumbosacral ectasia
Adolescent with hyperextensible skin, hypermobile Ehler–Danlos syndrome
joints, kyphoscoliosis, easy bruising, skin scarring,
mitral valve prolapse, and abnormal capillary
fragility test
Eight café-au-lait spots, freckling of the axilla, Neurofibromatosis type I
Lisch nodules, optic glioma, and pseudarthrosis of
the fibula
An 18-year-old boy with a family history of eighth Neurofibromatosis type II
cranial nerve masses presents with hearing loss,
tinnitus, loss of balance, blurring of vision, and
posterior subcapsular lens opacities on eye
examination
Adolescent presents with facial acne that is not Tuberous sclerosis
responding to treatment, has ash leaf
(hypopigmented macules), facial angiomas
(adenoma sebaceum), nail fibroma, pitting of
dental enamel, and renal angiomyolipomas

Infantile spasm is commonly associated with Tuberous sclerosis
Helpful sign to assist in early diagnosis of tuberous Ash leaf spots (hypopigmented macules)
sclerosis
Most common cardiac finding in infants with Cardiac rhabdomyomas
tuberous sclerosis
Newborn with long eyelashes, hirsutism, low Cornelia De Lange syndrome
hairline, downward-turned mouth, intrauterine
growth restriction (IUGR), thin upper lip,
micromelia, and syndactyly
Child with partial albinism, white forelock, Waardenburg syndrome
premature gray hair, iris heterochromia, cleft lip,
and cochlear deafness
Child with a history of hypoglycemia and Beckwith–Wiedemann syndrome
omphalocele at birth, coarse facial features, large
tongue, earlobe creases, posterior auricular pits,
Wilms tumor, and cryptorchidism
Infant with macrodactyly, hemihypertrophy, Proteus syndrome
lipoma, hemangioma, soft-tissue hypertrophy, and
accelerated growth
Newborn large for gestational age, macrocephaly, Soto syndrome
prominent forehead, hypertelorism, intellectual
disability, large hands and feet
Brachycephaly, frontal bossing, wormian bones, Cleidocranial dysostosis
hypoplastic or absent clavicles, delayed eruption of
deciduous teeth, and joint laxity
Early fusion of sagittal suture, and the head is long Scaphocephaly (the most common type of
and narrow craniosynostosis)
Newborn with craniosynostosis, brachycephaly, Apert syndrome
strabismus, hypertelorism maxillary hypoplasia,
beaked nose, proptosis, syndactyly, single nail,
broad thumb
Craniosynostosis, short stature, deviated nasal Crouzon syndrome
septum, malocclusion, malposed teeth, no limb
defects
Craniosynostosis, broad thumb and toes Pfeiffer syndrome
Tower or clover-leaf skull due to multiple fused Carpenter syndrome
sutures, preaxial polydactyly, obesity
Genetic counseling requires A specific diagnosis with known inheritance
mechanism
Indications for obtaining a karyotype: examples Unusual appearance, multiple congenital
anomalies, and/or possible mental disability
Child has a routine karyotype that reveals 47, To explain that their child has Down syndrome
XX+21. Appropriate counseling for the parents is due to aneuploidy and that they do not need to
have their chromosomes checked
Cytogenetic nomenclature for embryonic germ 47, XX+21
cells from a female fetus with the trisomy form of
Down syndrome would be
1036 O. I. Naga

A couple desires prenatal diagnosis because the Amniocentesis
woman is 39 years old. They want the safest and
most reliable form of prenatal testing
Child has obesity, compulsive overeating, and Obtain a green-top (heparinized) tube for the
underdeveloped genitalia, which make you suspect harvest of white cells with the indication of
Prader–Willi syndrome. You recall that FISH routine karyotype, including FISH for
testing for a chromosome 15 submicroscopic microdeletion 15
deletion may be diagnostic. The best approach for
obtaining a laboratory diagnosis
Chorionic villus sampling is performed at which 10–12 weeks of pregnancy
weeks of pregnancy?
Amniocentesis is performed at which weeks of 12–16 weeks of pregnancy
pregnancy?
Male with tall stature, speech and language delay, 47, XYY syndrome
learning disabilities, cystic acne in adolescence, no
facial dysmorphology, normal intelligence
Female with tall stature; speech/language delay; 47, XXX syndrome “triple X syndrome”
learning disabilities; normal intelligence, sexual
development, and fertility
Male infant with short webbed neck, low posterior Noonan syndrome
hairline, edema of hands and feet, mild intellectual
disability mutation of PTPN11 gene
A 10-year-old boy with progressive motor Juvenile Huntington disease (because of CAG
disability, cognitive decline, and psychiatric trinucleotide repeat expansion, clinical onset can
disturbances; his father had the same condition at occur in childhood) AD
age 40 years, died at age of 60
METABOLIC DISORDERS
Golder N. Wilson
Last-Minute Review—Metabolic Disorders Most Likely Answer

Newborn with a high ammonia level, normal anion Urea cycle defect (UCD)
gap, and respiratory alkalosis. What metabolic
disorder category is this likely to be?
Newborn with poor feeding, vomiting, elevated Citrullinemia-UCD
ammonia levels, and respiratory alkalosis and
elevated citrulline levels
Child presents with ammonia level 2000 μmol/L, Ornithine transcarbamylase deficiency
low BUN, with respiratory alkalosis without (OTC)-UCD
ketoacidosis and high levels of orotic acid
What are the initial steps of urea cycle defect Reduce protein intake, correct respiratory
(UCD) management? alkalosis
Normal to high ammonia level with a high-anion Organic acidemia
gap acidosis. What metabolic category is this likely
to be?

A neonate with severe ketoacidemia with or Propionic acidemia
without elevated ammonia level, and long-term
complication is associated with cardiomyopathy
Which metabolic disease can cause Isovaleric acidemia
encephalopathy and is associated with an odor of
sweaty feet?
Which metabolic disease presents with retinal Glutaric aciduria type I
hemorrhage and intracranial bleeding and can be
mistaken for child abuse?
A 1-week-old presents with severe metabolic Maple urine syrup disease
acidosis, poor feeding, opisthotonos, absent Moro Treatment: restrict leucine intake
reflex, seizures, and urine with a “caramel-like
odor”
What is the category of these amino acids: valine, Three branched-chain amino acids
leucine, and isoleucine?
A 6-month-old has alopecia, encephalopathy; skin Biotinidase deficiency or holocarboxylase
rash looks like acrodermatitis enteropathica synthetase deficiency
A 2-year-old girl presents with seizures, tachypnea, Medium-chain acyl-CoA dehydrogenase
and drowsiness; she has been having diarrhea, (MCAD) deficiency (due to fatty acid oxidation
vomiting, and loss of appetite for the last few days. defect, she is unable to increase ketone body
Her labs showed hypoglycemia, low ketones, and production after glucose consumption during
hyperammonemia fasting or metabolic stress due to illness)
Child presents with a musty odor, eczema, fair skin Phenylketonuria (PKU)
and hair, and intellectual disability
Newborn with positive PKU on newborn Start low-protein diet and a phenylalanine-free
screening. What is the next best step? medical formula as soon as possible. Then
confirm with genetic testing
What is the major consequence of delaying dietary Irreversible intellectual disability in most
restriction in children with PKU? children
Black pigments in the diapers, unusually dark Alkaptonuria
urine few days after birth; when older, develops
blue discolorations in the ear cartilage and palpable
calcifications in the discolored areas, arthritic
symptoms in the spine, hip and knee
Child with an intellectual disability, normal aorta, Homocystinuria (in Marfan syndrome the lens is
pectus excavatum, increased risk of clotting, along dislocated upward and no intellectual disability)
with downward dislocation of the lens (ectopia
lentis)
Infant with failure to thrive, hepatomegaly; renal Tyrosinemia type I (hepatorenal)
tubular acidosis may be associated with
hepatoblastoma
Type of tyrosinemia associated with intellectual Tyrosinemia type II (oculocutaneous
disability, corneal ulcers, and painful skin lesions tyrosinemia)
on the palms and soles
A 4-week-old infant presents with vomiting, Galactosemia (galactose 1-phosphate
seizure, jaundice, poor weight gain, uridyltransferase deficiency)
hepatosplenomegaly, cataracts, and reduced
substance in the urine
1038 O. I. Naga

Infant had sepsis before the diagnosis of Escherichia coli (E. coli)
galactosemia. What was the most likely cause?
Healthy infant presents with cataracts only. What is Galactokinase deficiency
the most likely cause?
A 4-month-old, doll-like face with prominent Type I glycogen storage disease (von Gierke
cheeks, short stature, thin extremities, protuberant disease)
abdomen, hepatomegaly, hypoglycemia, seizures,
lactic acidosis, hyperuricemia, and hyperlipidemia
What is the best management of infants with von Continuous feeding at night with nasogastric
Gierke disease? tube
Cramps with exercise, burgundy-colored urine McArdle disease (type V glycogen storage
after exercise, elevated creatine phosphokinase disease)
(CPK), and ammonia levels after exercise
A 6-week-old infant previously normal presents Pompe disease (type II glycogen storage
with muscle weakness, hypotonia, large tongue, disease)
hepatomegaly, hypertrophic cardiomyopathy,
congestive heart failure, elevated CPK,
transaminases, and LDH; muscle biopsy shows
vacuoles full of glycogen
A previously healthy 7-month-old infant with Fructokinase 1,6, diphosphatase deficiency
new-onset seizures, vomiting, and lethargy that
started after fruit juice was introduced
An 18-month-old with inguinal and umbilical Hurler syndrome
hernias, now presents with progressive Mucopolysaccharide (MPS) type I
developmental delay, coarse facial features,
macroglossia, macrocephaly > 95%,
hepatosplenomegaly, corneal clouding, retinal
disease, and deafness
An 18-month-old boy, previously healthy, presents Hunter syndrome
with progressive developmental delay, coarse facial MPS type II (X-linked recessive)
features, macroglossia, macrocephaly > 95%,
hepatosplenomegaly, no corneal clouding
Child previously normal presents with a Sanfilippo syndrome
progressive intellectual decline, temper tantrums, MPS type III
hyperactivity, destructive and aggressive behavior,
pica and sleep disturbances, now becomes
immobile and unresponsive
Acroparesthesia or episodes of extremities with Fabry disease (X-linked recessive)
burning pain, anhidrosis, fever, proteinuria,
hypertension, angiokeratomas (painless papules on
the skin), and clouding of the cornea
A 3-year-old of Ashkenazi Jewish presents with Gaucher disease type I
severe splenomegaly, lytic bone lesions, and
decreased glucocerebrosidase levels

A 2-month-old infant startles easily to any noise, Tay–Sachs disease
does not diminish with repeated stimuli, hypotonia,
progressive muscle weakness, extremity
hypertonia, large head, noises trigger seizures,
macular cherry-red spot, and no organomegaly
A 4-year-old child, dysphagia, abnormal eye Niemann–Pick disease
movement, ataxia, hepatosplenomegaly, cataplexy
when scared, and narcolepsy
Infant with a history of developmental delay, (MELAS) syndrome
Myopathy, Encephalopathy, Lactic Acidosis, and
Stroke
Ptosis, ophthalmoplegia, ragged-red fiber Mitochondrial DNA (mtDNA) mutation
myopathy
An 18-year-old develops ophthalmoplegia, night Kearns–Sayre syndrome
blindness, ataxia, heart block, muscle weakness,
proximal myopathy, short stature, and
hypogonadism
A 12-year-old, ataxia, hypoactive or absent deep Friedreich ataxia
tendon reflexes, impaired vibratory and
proprioceptive functions, hypertrophic
cardiomyopathy, and diabetes mellitus
Boy, biting his lips, and fingers; normal at birth, Lesch–Nyhan disease
had difficulty gaining weight in the 1st year of life,
uric acid level is elevated
What is the enzyme deficiency in patients with Hypoxanthine-guanine
Lesch–Nyhan disease? phosphoribosyltransferase (HGPRT)
How is Lesch–Nyhan disease transmitted? X-linked recessive
Loss of developmental milestones; failure to thrive; Menkes disease or kinky hair disease
truncal hypotonia; abnormal kinky hair, eyebrows,
and eyelashes
How is Menkes disease transmitted? X-linked; causes an impaired copper intake
Child with cholesterol 650 mg/dL, tendon Familial hypercholesterolemia
xanthoma, father died at age 23 with a heart attack
MENTAL AND BEHAVIORAL HEALTH
Osama I. Naga
Last-Minute Review—Mental and Behavioral

Health Most Likely Answer
A 3-year-old boy is frequently reaching for his Masturbation (distract the child to stop)
genitalia; his face becomes flushed; he is sweating
and starts to breathe irregularly, stops when parents
distract him
1040 O. I. Naga

A 2-year-old girl frequently postures her lower Masturbation (seizure will not stop with
extremities and keeps crossing her legs in a distraction)
repetitive movement; she stops when her mother is
distracting her; the mother is concerned about her
having a seizure
What is the best management of masturbation in Guide the child to limit the behavior. Otherwise,
children? it is a normal behavior
A 2-year-old boy is sucking his thumb mostly Reassurance (most children will outgrow the
when he is tired, hungry, or sad. What is the best habit by 4 years of age)
recommendation?
A 6-year-old boy with thumb sucking behavior. He Positive reinforcement, aversive techniques,
is bullied and teased in school. He has dental competitive responses, and orthodontic devices
malocclusion. What is the best recommendation? (intervention if > 4 years of age)
A 6-year-old boy wakes up in the middle of the Nightmares—reassurance (television viewing
night scared; he remembers a giant dinosaur was should be avoided for about 2 h prior to
trying to eat him bedtime)
The parents of a 4-year-old girl have noted Night terrors—reassurance (preemptive
episodes of screaming, intense fear, with difficulty awakening before the episodes and safety
of arousal that occur several times per week; she precautions)
does not remember the episodes
Adolescent female presents with numbness and Conversion disorder
difficulty moving her legs. All lab results and
imaging studies are normal. The patient has been
feeling stressed as a result of school
A 7-year-old boy exposed to a horrific car Acute stress disorder
accident; father died in the accident. Boy has 3 days to 1 month after exposure
difficulty sleeping, a flashback of the event,
recurrent distressing dreams for 3 weeks after the
accident
A 7-year-old boy exposed to a horrific car Post-traumatic stress disorder (6 months after
accident; father died in the accident. Boy has exposure)
difficulty sleeping, a flashback of the event,
recurrent distressing dreams for 6 months after the
accident
Two siblings are jealous of each other and are Focus on individual needs of each child, giving
always fighting each other in front of their parents. each the time and attention needed, to feel loved
“Sibling rivalry.” What is the best approach? and secured
Exposure to which substances during the prenatal Cocaine, alcohol, and tobacco
period is associated with aggressive behaviors in
children?
Two siblings are fighting and hurting each other They should be separated, and told violence is
physically not allowed

What is the best way to discipline a 3-year-old boy Time out—1 min for each year of age
who is misbehaving? Ensuring that the reward is developmentally
appropriate
Corporal punishment is NOT recommended as a
method of discipline
What is the best method of discipline Limit privileges and establish boundaries
recommended for an adolescent?
A 2-year-old boy is crying hysterically and Acknowledge his frustration, take him in safe
banging his head while the mother and father are place letting him ride out the tantrum
in a restaurant
Mother is worried about autism in the above Headbanging in isolation with a tantrum is not a
instance because of headbanging and frequent red flag of autism
outbursts
A 4-year-old boy is frightened of dogs Show him pictures of dogs, then videos, then toy
dog, then finally a real dog
Child is adaptable to new situations, regular Easy temperament
sleeping, and eating patterns, less demanding, and
cheerful
Child with intense emotional reactions adapts Difficult temperament
poorly to new situations, unpredictable, lower
sensory threshold, moody and negative
Child initially withdraws from new situations, Slow to warm temperament
observes hesitantly before entering a new activity,
moderate negative response, and gradually warms
up to the new situations
What is the best management of temperaments? Reassurance (will learn to moderate their own
temperamental reactions as they grow older)
Adolescent with 2 weeks of depressed or irritable Cognitive behavioral therapy (CBT)
mood, decreased pleasure, still going to school and
doing homework, no suicidal thoughts. What is the
best initial treatment?
Adolescent with 2 weeks of depressed, irritable Cognitive behavioral therapy (CBT) and
mood, decreased pleasure, lack of interest in medication
activities, and suicidal thoughts. What is the best
initial treatment?
What are the SSRI medications approved by the Fluoxetine and escitalopram
US Food and Drug Administration (FDA) for the
treatment of depression in adolescents?
What does CBT aim to achieve? To reframe present negative thoughts into
healthier thoughts, resulting in more positive
feelings and behaviors
A 6-year-old boy with significant receptive and Fragile X syndrome
expressive language problems; he is in special
education classes, has difficulty with changes and
sensory sensitivity. He bites his hands frequently
and avoids eye contact. What is the most likely
underlying condition?
1042 O. I. Naga

At what age are the dysmorphic features of fragile Around the time of puberty
X syndrome, such as a long face, prominent jaw,
and macroorchidism, usually seen?
What is the most common cause of inherited Fragile X syndrome
intellectual disability?
What is the most likely cognitive deficit in boys Moderate ID (average IQ ~41), girls are more
with a full mutation (> 200 CGG repeats) in cases mildly affected
of fragile X syndrome?
What is the best test to confirm the diagnosis of Fragile X DNA analysis
fragile X syndrome
Mother is concerned about possible speech delay No significant difference between 1 and 2
in her 2-year-old, who is currently exposed to 2 languages exposure in speech development
languages at home
Mother is concerned because her 6-year-old has a Reassurance (certain speech sounds may not be
problem with certain speech sounds, but the child’s well articulated until 8 years of age)
speech is 100% intelligible to strangers
Child with speech and language delay. What is the Formal audiology evaluation
next best step?
A 2-year-old boy presents with speech delay, no Refer the child to early intervention (EI) for
eye contact, does not share any activities with evaluation of autism spectrum
other children. Physical examination is normal.
What is the next best step?
A 3-year-old boy presents with speech delay, no Refer to the school district for evaluation of
eye contact, does not share any activities with autism spectrum
other children. Physical examination is normal.
What is the mainstay of autism spectrum disorder Applied behavioral analysis (ABA), speech and
treatment? occupational therapies
What is the etiologic workup in classic cases of None; it is a clinical diagnosis
autism spectrum disorders?
What is the etiologic workup in cases of autism DNA analysis for fragile X syndrome and a
spectrum disorders associated with intellectual chromosome microarray analysis
disability or global developmental delay?
Adolescent with several antisocial behaviors, Cognitive behavioral therapy, family therapy,
defiance, rule-breaking, vandalism, and aggression. and behavior management training
What is the best management?
An 8-year-old boy is struggling academically, no Summer school, after school programs, tutoring,
specific learning disability has been identified by and early reading programs
the school. What is the next best step?
What is the disadvantage of grade retention in High risk of dropping out of high school, and
students who are struggling academically? ultimately employment problems
A 10-year-old girl is struggling in school; parents Psychoeducational evaluation request in writing
are concerned because of her poor grades. What is from parents to her school
the next best step?

What is the role of pediatricians in children with Review the initial psychoeducational evaluation
learning disabilities upon diagnosis? and child’s report card with the family.
Make sure that the child is receiving
remediation, accommodations, modifications,
and therapies.
Investigate for related disorders, such as
attention deficit hyperactivity disorder (ADHD),
adjustment disorder, or anxiety disorder.
An example of a child who may benefit from the Child with ADHD. Section 504
504 plans (Accommodation) of the US Rehabilitation Act
of 1973 covers kids with disabilities who do not
require specialized instruction
(504 school accommodations for peanut allergy
is another example)
Examples of accommodations in school under 504 Preferential seating, extended time for testing,
for children with ADHD modifications in classroom assignments
Which child may benefit from the US Individuals Specific learning disability, e.g., dyslexia,
with Disabilities Education Act (IDEA), providing dysgraphia, dyscalculia
qualified children with an Individualized Education Others, e.g., autism, deafness, vision
Program (IEP)? impairment, intellectual disability
Can a child with ADHD qualify for IEP? Yes, if he or she requires specialized instructions
The first-line treatment of ADHD Stimulant medications, e.g., methylphenidate
Indications of non-stimulant medications (e.g., Preference of parents
atomoxetine, guanfacine, clonidine) in the Poor response or significant side effects with
treatment of ADHD stimulant medications
Concerns about substance/stimulant abuse or
significant tics
What is the significance of IQ test scores greater Intellectually disabled range
than 2 SD below the mean (< 70) in both cognitive
and adaptive measures?
An 8-year-old girl underwent psychoeducational Specific learning disability in math
testing, and her aptitude test score in IQ was within
normal range, her academic achievement scores
were within normal in reading, and writing, but in
math her score was < 70
The girl in the previous example qualifies for IEP special education program
which of the following: 504 plan or IEP?
Participation of children with and without Educational inclusion
disabilities in the same educational settings
What are the benefits of educational inclusion? Promotes tolerance, empathy, and collaboration
among students
Independent in personal care and activities of daily Mild intellectual disability (ID)
living with minimal support, education level up to
sixth grade, independent employment with a
possible need for minimal support or supervision
1044 O. I. Naga

Can care for personal needs and activities with Moderate ID
limited support, education level up to third grade;
difficulty understanding time and money,
supportive living such as in a group home,
supported, or supervised job, unskilled or semi-
skilled work
EMERGENCY MEDICINE
Jennifer McConnell and Kenneth Yen
Last-Minute Review—Emergency Medicine Most Likely Answer

A 27-day-old with fever 103 °F for 1 day, feeding Full sepsis evaluation (blood, urine and CSF
well, no cough, no vomiting, no diarrhea. Physical testing) and empiric IV antibiotics
examination is normal. What is the next best step?
An 8-week-old with fever 103 °F for 2 days, Complete blood count (CBC), urinalysis and
feeding well, no cough, no vomiting, no diarrhea. urine culture (infants < 90 days of age with a
Physical examination is normal. What is the next temperature > 38 °C should be promptly
best step? evaluated)
A 15-month-old with fever 103 °F for 2 days, Reassurance (most likely viral syndrome, advise
feeding well, fussy when fever is high, playful for close follow-up)
brief periods after receiving antipyretics, no cough,
no vomiting, no diarrhea. Physical examination is
Non-toxic, fully vaccinated toddler with nasal Oral dexamethasone (viral croup)
congestion has a barky cough, inspiratory stridor
when agitated, but no resting stridor. What is the
next best step?
A well-appearing, 12-month-old with upper Clearance of nasal secretions and reassurance
respiratory infection (URI) symptoms and fever (acute viral bronchiolitis)
presents with diffuse wheezing on lung
auscultation. What is the next best step?
Child with asthma, presenting with chest pain, Albuterol and ipratropium nebulizer treatments
chest tightness and diffuse bilateral expiratory with oral steroids
wheezing in the setting of URI symptoms. What is
the next best step?
Distressed, vaccinated toddler, with sudden onset Attention to ABCs (airway, breathing,
of cough and inspiratory stridor while eating circulation) and emergent subspecialty
peanuts. What is the next best step? evaluation for a suspected foreign body in
airway
An unvaccinated child with inspiratory stridor at Attention to ABCs (airway, breathing,
rest, toxic appearing, leaning forward and drooling. circulation) and emergent subspecialty
Next best step? evaluation for suspected epiglottitis
Child with peanut allergy presents with diffuse IM epinephrine for anaphylaxis
hives and flushed skin after ingestion of peanuts,
noted to have hypotension on initial vital signs.
What is the definitive treatment for the underlying
diagnosis?
Child presents to the emergency department (ED) Wound cleaning with adequate pressure
with a dog bite. What is the next best step? irrigation

After cleaning the wound of dog or cat bite, what Amoxicillin/clavulanate, cover both aerobes and
is the most appropriate prophylactic antibiotic? anaerobes, especially Pasteurella
Dog or cat bite and allergy to penicillin Clindamycin plus
trimethoprim-sulfamethoxazole
Teenage patient punches another student in the Amoxicillin/clavulanate, cover both aerobes and
teeth during an altercation at school and sustains anaerobes, especially Eikenella
puncture lacerations to knuckles; what is the most
appropriate prophylactic antibiotic?
A fully vaccinated child with a bite from a stray Rabies prophylaxis (rabies vaccine and rabies
dog that was not captured. The child was admitted immunoglobulin) and intravenous
on NPO status due to multiple puncture lacerations ampicillin-sulbactam
requiring surgical repair. What is the next best
treatment?
Adolescent with pain, redness, and tenderness in Tdap vaccine and oral ciprofloxacin
the foot after stepping on a rusty nail that Pseudomonas aeruginosa infection
punctured the foot. There is no fever and the rest of
the exam is normal. Last tetanus vaccine was
7 years ago. What is the best treatment?
Child with a sudden stinging sensation in the right Brown recluse spider bite (local pain, necrosis,
foot after playing in the basement, within a few and less systemic manifestations)
hours develops severe pain and enlarging erythema
in the right foot, which 2 days later becomes a
hemorrhagic blister surrounded by an
erythematous halo and dark eschar. What is the
most likely cause?
Child presents with sudden pinching sensation in Black widow spider bite (initial pinch or
the foot after playing in the basement, within 8 h pinprick sensation, or unnoticed bite followed by
develops muscle cramping in the right leg, which significant systemic manifestations, muscle
progresses to the back and abdomen. O/E: elevated cramping, tachycardia, and hypertension)
blood pressure, tachycardia, tender abdomen,
target-like appearance redness in the foot. What is
Child stung on the left arm by a wasp, having pain, Removal of the stinger, application of cool
itching, erythema, and mild swelling in the left arm compresses or ice packs, and mild oral
without any signs of systemic illness. What is the analgesics and oral antihistamines to help
best treatment? alleviate pruritus
A 1-year-old falls < 3 ft height, no loss of Reassurance (very low risk of clinically
consciousness, no headache, no vomiting. Physical significant traumatic brain injury [height of fall
examination is normal except mild swelling in the in < 2 years of age > 3 ft is a high risk])
forehead. What is the next best step?
A 3-year-old falls < 5 ft height, no loss of Reassurance (very low risk of clinically
consciousness, no headache, no vomiting. Physical significant traumatic brain injury [height of fall
examination is normal except mild swelling in the in > 2 years of age > 5 ft is a high risk])
forehead. What is the next best step?
A 6-year-old boy fell and hit his head while Observation period 4–6 h in ED
running, loss of consciousness for 30 s, one-time
vomiting, headache that has slightly improved in
the last 30 min. Physical examination is normal
except mild swelling in the forehead. What is the
next best step?
1046 O. I. Naga

Child brought to the ED after severe head trauma, Attention to ABCs (airway, breathing, and
continues to have persistent vomiting and altered circulation)—the child needs CT head but first
level of consciousness. What is the next best step? requires stabilization
A 6-year-old boy fell and hit his head, loss of Head CT scan without contrast
consciousness for 2 min, progressive headache,
persistent vomiting. Physical examination is
normal except mild swelling in the forehead. What
is the next best diagnostic test?
A 6-year-old boy fell and hit his head, loss of Epidural hematoma—convex toward the brain
consciousness, headache, vomiting, improvement and restricted by suture lines in CT scan
for few hours (lucid interval) followed by
deterioration of symptoms and loss of
consciousness. CT head shows hyperdense
lenticular-shaped mass situated between the brain
and the skull. Most likely diagnosis?
Head trauma, severe headache, and drowsiness. Subdural hematoma—concave toward the brain
Head CT scan showed hyperdense (white), and unlimited by suture lines in CT scan
crescent-shaped mass between the inner table of
the skull and the surface of the cerebral
hemisphere. Most likely diagnosis?
Head trauma, bleeding from the ear, hearing loss, Temporal bone fracture
and facial paralysis. Most likely injury?
Head trauma, ecchymosis behind the ear (battle Basilar skull fracture
sign), periorbital ecchymosis (raccoon eyes),
abducens nerve paralysis. Most likely injury?
Glasgow Coma Scale (GCS) of a child after head GCS = 10 (3 E/2 V/5 M)
trauma who opens eyes only to sound, makes a few
unintelligible sounds but does not say words, and
localizes to pain
Effect of clonidine, cholinergic, opiates, Miosis
organophosphates, phencyclidine, phenothiazine,
pilocarpine, and barbiturates (sedatives) on the
pupil
Effect of atropine, antihistamines, antidepressants, Mydriasis
amphetamine, and cocaine on the pupil
Ingestion of which agents can cause seizures, Anticholinergic agents (e.g., amitriptyline,
hyperthermia, agitation, decreased urine output, diphenhydramine, jimson weed, or deadly
anhidrosis, flushing, and mydriasis? nightshade)
Ingestion of which agent can cause pinpoint pupils, Opiate intoxication
unresponsiveness, and respiratory depression?
What is the treatment of choice for opiate Naloxone
poisoning?
Child presents with neck spasms, oculogyric crisis, Diphenhydramine; the patient has an acute
and tongue thrusting after accidental ingestion of dystonic reaction
promethazine (anti-nausea medication). What is
the drug of choice to treat these symptoms?
Child ingests a large amount of a grandparent’s Aspirin
medicine, presents with hyperventilation,
metabolic acidosis, high-anion gap, tinnitus, and
confusion. Likely ingestion?

Healthy child ingests caretaker’s medicine, Tricyclic antidepressants (TCA) toxicity
presents with altered mental status, seizure,
drowsiness, lethargy, sinus tachycardia, widened
QRS, prolonged QT interval. Likely ingestion?
Adolescent currently on SSRI treatment for Serotonin syndrome—hallmark is myoclonus
depression presents with confusion, sweating, and Occurs with: monoamine oxidase inhibitor
myoclonus admits to trying ecstasy at a party. (MAOI) and linezolid
Likely cause of symptoms?
Child is brought to the ED after ingesting Lactic acidosis
numerous pills of metformin. Possible laboratory
finding?
Child presents with nausea, vomiting, abdominal Iron
pain 6 h after accidental ingestion of pills, felt
better for a short period, then 24 h later presents
with metabolic acidosis, shock, hepatic failure, and
6 weeks later develops pyloric and gastrointestinal
scarring. What is the most likely ingested
substance?
Child reaches the toxic level of acetaminophen 4 h N-acetylcysteine (NAC)
after accidental ingestion. What is the antidote?
Toddler ingests a small amount of windshield Immediate referral to the ED for further
wiper fluid about 30 min before the presentation, is laboratory testing (toxic alcohol ingestion→
asymptomatic. Caretaker calls primary care office methanol)
for advice. What is the next best step?
Adolescent presents with slurred speech, Ethylene glycol
tachypnea, cyanosis, pulmonary edema, renal
failure, calcium oxalate crystals in the urine,
high-anion gap metabolic acidosis. Likely
ingestion?
Adolescent presents with visual disturbance, Methanol
abdominal pain, and high-anion gap metabolic
acidosis. Likely ingestion?
Child accidentally ingests window cleaner, Caustic ingestion, immediate subspecialty
presents with sore throat, dysphagia, and drooling. consultation for endoscopy
Next best step?
Child complains of a headache, weakness, fatigue, Carbon monoxide poisoning (measurement of
and nausea for 2–3 weeks since the start of winter, carboxyhemoglobin on blood gas)
caretaker reports self and 2 other siblings are
feeling the same. Most likely exposure?
Child at a party ate some cookies then starts IM epinephrine at 0.01 mg/kg
vomiting, swelling of the lips, and trouble
breathing, should be treated with which medication
Toddler presents with right arm pain and decreased Nursemaid’s elbow (annular ligament
arm mobility after being lifted up by the right arm displacement)
during play. No falls or trauma reported. Most
likely diagnosis?
Child tripped and fell on an outstretched hand Occult supracondylar fracture
presents with tenderness to distal humerus. No
obvious fracture on elbow radiograph, although
there is a posterior fat pad sign on the lateral view.
Most likely diagnosis?
1048 O. I. Naga

Term neonate delivered vaginally had difficulty Clavicular fracture with healing callus from a
with vacuum extraction presents with “bump” over traumatic birth
left clavicle 2 weeks after birth. Most likely
diagnosis?
Chest radiograph performed on a healthy infant for Non-accidental trauma/child abuse
evaluation of chronic cough reveals many callus
formations to the posterior ribs bilaterally. Most
likely diagnosis?
Toddler presents with left leg pain and limps after Toddler’s fracture
going down a slide and getting the left foot stuck
and twisted on the edge of the slide. Radiograph of
lower leg reveals a non-displaced spiral fracture of
the lower third of the tibia. Most likely diagnosis?
Which type of burn is associated with mild pain, Superficial burn (formerly 1st-degree burn)
swelling, and redness that blanches with pressure?
Which type of burn is associated with severe pain, Partial thickness burn (formerly 2nd-degree
blebs, and blisters? burn)
Which type of burn is painless with a dry and Full-thickness burn (formerly 3rd-degree burn)
leathery appearance?
Child has electrical burns to the mouth after Refer to burn surgeon—concern for labial artery
chewing on an electrical cord. Next best step? bleeding
Child who weighs 20 kg has burns on 5% of the Parkland formula: 4 ml/kg/% of the burn area of
body surface area. What IV fluids should be given lactated Ringer’s
and how much? Total: 400 mL with 200 mL (50% of total) given
in the first 8 h and 200 mL over the next 16 h
A toddler who presents with scald burns over legs Evaluation for intentional injury/abuse
in a stocking distribution (clearly demarcated)
needs what further evaluation
Toddler presents with sudden onset vomiting and Ileocolic US to rule out intussusception
lethargy, bedside point-of-care glucose and venous
blood gas are normal with a non-focal neurologic
exam, soft abdomen, and no concern for ingestion.
Next best test?
Toddler presents with intermittent screaming Ileocolic
episodes followed by periods of normalcy;
caretaker reports a pink “jelly”-like stool. Most
likely location of the intussusception?
Adolescent female with acute onset of severe left Pelvic US to rule out acute ovarian torsion
lower pelvic pain, nausea, and vomiting; exam
reveals severe tenderness and guarding in the left
lower quadrant. Next best test?
Adolescent male with acute onset of severe right Testicular US to rule out acute testicular torsion
testicular pain with nausea and vomiting; exam
reveals high riding testicle with absent cremasteric
reflex. Next best test?
Child with 1 day of nonbilious emesis and Acute appendicitis
diarrhea, fever, periumbilical abdominal pain, and
tenderness that is radiating to the right lower
quadrant. Most likely diagnosis?
What is the initial imaging study of choice in cases Abdominal US
of suspected acute appendicitis?

A 4-week-old with 10 days of worsening projectile Hypokalemic, hypochloremic metabolic
vomiting and 1 day of intermittent apneic spells, alkalosis
found on ultrasound to have hypertrophic pyloric
stenosis. Most likely laboratory finding?
A healthy infant with 1 day of intermittent bilious Upper GI series to rule out malrotation
emesis. Stable vital signs on arrival. Next best test?
CRITICAL CARE
Last-Minute Review—Critical Care Most Likely Answer

Child sustained blunt trauma to the abdomen, all For hemodynamically stable grades I–III,
vital signs are normal, and the abdominal conservative management with monitoring of
ultrasound (US) is positive for splenic rupture. vital signs, surgical consult, serial hemoglobin,
What is the best management? and hematocrit measurements
Child sustained blunt trauma to the abdomen, low Abdominal exploration
blood pressure, tachycardia, cold, clammy skin,
and abdominal US is positive for splenic rupture.
Child presents with nausea, vomiting, and malaise. Acute hepatic failure
O/E: the liver is slightly enlarged. Laboratory
findings include elevated liver enzymes, high
direct bilirubin, hypoglycemia, and prolonged
prothrombin time. What is the most likely
diagnosis?
Child presents to the ED with rapid breathing, low Cardiac tamponade
blood pressure, and normal oxygen saturation.
O/E: tachypnea, tachycardia, clear lungs, and
muffled heart sounds and widened pulse pressure.
What is the most likely diagnosis?
A 12-year-old girl was transferred to the ED after Flail chest
a car accident. She is complaining of chest pain on
the left side and difficulty breathing. O/E: vital
signs are normal; however, she has fast and
shallow breathing, a segment of the left chest
moves inward upon inspiration and outward upon
expiration. What is the most likely diagnosis?
What is the next best step in the previous case of Pain control, pulmonary toilet. Ensure adequate
flail chest? ventilation and oxygenation
1050 O. I. Naga

A 5-year-old boy with 2 days history of severe Hypovolemic shock (low intravascular volume)
vomiting and diarrhea. He is lethargic and not able
to drink by mouth. O/E: awake but minimally
interactive, low-grade fever, tachypnea,
tachycardia, low blood pressure, delayed capillary
refill time, cold skin, dry mucous membranes, skin
tenting, and diminished peripheral pulses. What is
the most likely diagnosis?
What is the next step in the previous case? Aggressive fluid resuscitation: 20 ml/kg bolus
of normal saline or Ringer’s lactate over
5–10 min, additional boluses may be required
based on clinical assessment and ongoing losses
A 2-month-old with a history of congenital heart Cardiogenic shock
disease presents with hepatomegaly, and
cardiomegaly, 20 ml/kg of normal saline leads to
new crackles, worsening hypotension, and
tachycardia. What type of shock is this?
Type of shock that is associated with bradycardia, Neurogenic shock
hypotension, and is often associated with spinal
cord injury?
A 5-year-old boy with high fever 104 °F for Septic shock (cold shock)
2 days. He is lethargic and not able to drink by
mouth. O/E: awake but minimally interactive,
temperature 104.9 °F, ill-looking, tachypnea,
tachycardia, low blood pressure, delayed capillary
refill time, diminished peripheral pulses. WBC
count is 29,000. What is the most likely diagnosis?
The patient in the previous example continues to Start epinephrine infusion
have low blood pressure, refractory to fluid
resuscitation and antibiotics in the first 15 min.
A 5-year-old boy stung by a bee rapidly developed Epinephrine IM immediately
hives, pruritus, facial swelling, wheezing,
difficulty breathing. His blood pressure is low.
A 3-year-old girl arrived in PICU with prolonged Neurological exam followed by apnea test (after
cardiac arrest after choking on a hot dog. Her 24 h of supportive care)
pupils are dilated and fixed, absent gag reflex,
absence of spontaneous eye movements during
oculovestibular and oculocephalic testing. No
spontaneous movement. Lack of any respiratory
effort without ventilatory support. What is the next
best step to confirm brain death?

Child presents with no pulse; the EKG shows Defibrillate 2 J/kg
ventricular tachycardia. What would be the next
step in the management of the arrhythmia?
Child presents with tachycardia, hypercarbia, Malignant hyperthermia
generalized muscle rigidity, and hyperthermia IV dantrolene
immediately after surgery. What is the diagnosis
and treatment?
What is the most important poor prognostic factor Submersion time > 5 min
in near drowning?
Child was found submerged in the pool, is Call for help and begin chest compressions
unconscious and not breathing; what is the next
best step?
What is the best way to confirm successful ETT Colorimetric capnography
placement?
What is the depth of CPR compression for infants One-third the depth of the chest
through puberty?
What is the ratio of chest compressions to breaths 30:2
in single rescuer CPR?
What is the ratio of chest compressions to breaths 15:2
in 2-rescuer CPR?
What is the age range in which pediatric 1–8 years
defibrillator pads should be used?
A 6-year-old boy is in cardiac arrest, a pediatric Use the adult defibrillator/adult pads
defibrillator is not available, but an adult AED is
present. What should be done?
A 15-year-old male presents after an ATV Neuroprotective measures, including emergent
accident. He is bradycardic, GCS is 7, and the endotracheal intubation
right pupil is dilated and unresponsive. What are
the next steps in management?
Neurosurgery places an intracranial monitoring More than 50 mmHg (less than 5 years of age
device in the previous case. What would be the > 40 mmHg, 6–17 years of age > 50 mmHg)
target cerebral perfusion pressure (CPP) for this
age?
What is the size of the ETT for a 4-year-old child? 5 mm uncuffed
4–4.5 mm cuffed
What is the recommended sequence of CPR per C-A-B-D:
PALS guidelines? Circulation—Airway—Breathing—Defibrillate
For which type of cerebral edema is Vasogenic
dexamethasone indicated?
1052 O. I. Naga

A patient with persistent intracranial hypertension Uncal herniation
now has unilateral third nerve palsy and unilateral
fixed dilated pupils deviating downward and
laterally. What is the type of herniation?
In the above scenario, what would be the likely Midbrain
location of this constellation of symptoms in the
brain?
INFECTIOUS DISEASES
Matthew B. Laurens
Last-Minute Review—Infectious Diseases Most Likely Answer

Diarrhea and turtle at home Nontyphoidal Salmonella
Childcare center, fever, vomiting, bloody diarrhea, Shigella
new-onset seizure, leukocytosis, bandemia, and
rectal prolapse
Diarrhea, high BUN/creatinine, thrombocytopenia, Hemolytic uremic syndrome E. coli O157: H7
and hemolytic anemia
Child with his family to the Bahamas on a cruise Norovirus outbreak
ship, all of them have diarrhea, and a large number
of people on the ship have the same
Child had rice in a restaurant, presents with Bacillus cereus
vomiting and diarrhea
Child ate potato salad 3 h ago, presents with sudden Staphylococcus aureus (preformed enterotoxin)
onset of nausea, vomiting, severe abdominal
cramps and diarrhea
Adolescent recently had grilled rare pork meat Yersinia enterocolitica
presents with acute right lower quadrant (RLQ)
abdominal pain, normal appendix on abdominal US
Child living in a farm and has been drinking Campylobacter jejuni
unpasteurized cow milk, presenting with fever,
bloody diarrhea, and vomiting. What is the most
likely cause?
Campylobacter is associated with which of the Guillain–Barré syndrome
following neurological conditions?
A 6-month-old infant presents with constipation, Botulism
and poor feeding (mother tried honey for the first
time)
What is the best test to confirm the diagnosis in the Detection of botulism toxins or spores in stool
previous case with suspected botulism?
Community outbreak of diarrhea, news reports that Cryptosporidium
the drinking water has been contaminated with
acid-fast protozoa

What are the common pathogens causing Cryptosporidium, Shigella, Giardia, norovirus,
recreational water-associated outbreaks of acute and E. coli O157: H7
gastroenteritis
Traveled to Mexico; foul smelling diarrhea, with Giardiasis
burping and flatulence
Traveled to Mexico; bloody diarrhea, tenesmus, Amebiasis (Entamoeba histolytica)
and without fever
Patient with bloody diarrhea with mucus, fever, Entamoeba histolytica
abdominal pain, liver abscess and recent travel to Treatment: metronidazole plus paromomycin
Mexico
What is the best diagnostic test in cases with Serum antibodies to Entamoeba histolytica
suspected invasive amebiasis?
Unimmunized and buccal cellulitis Haemophilus influenzae type b (Hib)
Adolescent presents with, pneumonia, diarrhea, Legionella pneumophila
headache, and confusion
Adolescent presents with, cough, low-grade fever, Chlamydia pneumoniae
headache, wheezing, and negative cold agglutinins
A 3-day-old newborn, copious purulent eye Gonococcal conjunctivitis
discharge, and eyelid edema
Erythromycin ointment is considered the best Gonococcal, and nongonococcal non-
regimen for prophylaxis against neonatal chlamydial pathogens (does not prevent
conjunctivitis because of its efficacy against Chlamydia trachomatis transmission from
mother to infant)
A 6-week-old, staccato cough, and eye discharge Chlamydia trachomatis
A 3-month-old presents with a staccato cough, no Chlamydia trachomatis
fever, and chest radiograph positive for pneumonia
A 16-year-old with fever, recurrent non-productive Chlamydia psittaci
cough, and malaise; patient was exposed to exotic
birds in South America
Breeds turkey, high fever, pneumonia, muscle pain, Chlamydia psittaci
and splenomegaly
Fever of unknown origin with elevated liver Brucella, blood culture is the best test and treat
enzymes, lives on a farm, the most likely cause with doxycycline + rifampin
Tick bite, fever, rash, myalgia, headache, Ehrlichiosis
pancytopenia, elevated liver enzymes, and
hyponatremia
Tick bite, fever, rash on palms and soles, headache, Rocky Mountain spotted fever (RMSF)
joint pain, low platelet, and hyponatremia Rickettsia rickettsii
A 4-year-old with RMSF. What is the drug of Doxycycline
choice?
Connecticut, target skin lesion (erythema migrans), Treat (Lyme disease); do not order serology
next step
Child was camping in a park in New York, Order Lyme serology and treat if positive
developed Bell’s palsy, no rash, no other symptoms
A mother found a tick attached to her child’s thigh Ticks should be removed by using forceps or
tweezers without twisting or crushing
1054 O. I. Naga

Child visited Oklahoma with family, they hunted Tularemia (Francisella tularensis)
and skinned rabbits, the child presented with a large
lymph node in the groin, and fever
Neonate, peripherally inserted central catheter Remove the catheter and start IV antifungal
(PICC) line is positive for Candida albicans
Most common electrolyte disturbances associated Hypokalemia
with amphotericin B therapy Hypomagnesemia
Infant presents with 3 days of high fever, febrile Human herpesvirus 6 infection (roseola
seizure, develops a rash when fever resolves infantum)
Fever, headache, runny nose, rash on the cheeks Erythema infectiosum (parvovirus B19)
(looks like slapped), lacy rash on both arms
Very high fever, cough, coryza, conjunctivitis, Measles
bluish-gray specks on the buccal mucosa, the
maculopapular rash spreading from the head down,
splenomegaly, and lymphadenopathy
Child with mumps. For how long should children 5 days from onset of parotid gland swelling
with mumps be excluded from school?
During school outbreak of mumps. For how long At least 26 days after the onset of parotitis in
unimmunized children should be excluded from the last person with mumps in the affected
school? school
Posterior auricular and suboccipital German measles (rubella)
lymphadenopathy, headache, eye pain, sore throat,
maculopapular rash, low-grade fever, and chills
Newborn with microcephaly, chorioretinitis, Cytomegalovirus (CMV)
periventricular calcification and a major cause of
sensorineural hearing loss
Newborn with microcephaly, subcortical Congenital Zika syndrome
intracranial calcifications, eye anomalies, and
hyperreflexia. Mother immigrated from Brazil
2 months before giving birth in the USA. She
recalls having a fever in the first trimester
A fully immunized 6-year-old presented with Varicella zoster—may have mild episode even if
malaise, low-grade fever, and a mild vesicular rash vaccinated
that resembles “dew drops on a rose petal”
Child is born to a mother who is diagnosed with If the mother is diagnosed from 5 days before
varicella. When should the varicella zoster birth to 2 days after birth
immunoglobulin (VZIG) be given?
A 5-year-old male with sudden onset of high fever Influenza
during the month of March; he has body aches,
chills, sore throat, and generalized fatigue
A 20-month-old boy with sudden onset of high Start oseltamivir and order influenza molecular
fever 105 °F during the month of January. He has a assays (no need to wait for the result in high-
runny nose, cough, and malaise. O/E: he has nasal risk children before starting the medicine)
flaring and retractions, bilateral rhonchi. Rapid
influenza and respiratory syncytial virus (RSV)
tests are negative. What is the next best step?

Who is at risk of hospitalization and development Children younger than 2 years or who have
of complications caused by influenza infection? underlying medical conditions
What is the sensitivity of rapid diagnostic influenza Ranges from 10% to 70% (negative test result
assays test? does not rule out influenza)
What is the sensitivity of influenza molecular Ranges from 86% to 100%
assay?
A 3-year-old male never vaccinated against From 6 months to 8 years, if never received a
influenza should receive how many doses? previous influenza vaccine, 2 doses separated by
1 month are needed, then annually afterward
What is the most common cause of croup in Parainfluenza virus
children?
A 4-month-old unvaccinated child with profuse Rotavirus
foul-smelling diarrhea, dehydration, and electrolyte
abnormalities
An 8-year-old female with recurrent cold sore on Herpes labialis (HSV-1)
her lower lip
A 16-year-old sexually active male is complaining HSV-1 or HSV-2
of painful vesicles noted on the penis
A 14-year-old with a history of severe eczema Eczema herpeticum
presents with diffuse clusters and vesicles noted on Treatment: acyclovir
the affected area
A 16-year-old sexually active female presents with HPV—strains 6 and 11 are commonly
cauliflower-like lesions in the genital region associated with anogenital warts
Which strains of HPV are more commonly HPV—strains 16 and 18
associated with cervical cancer?
Adolescent male present with mumps (parents are Epididymo orchitis, arthritis, encephalitis
asking about the possible complications)
Chickenpox rash is infectious for how long? 1–2 days before the rash, and until all lesions
are crusted over
Limping, after stepping on a nail with a shoe on Pseudomonas aeruginosa
Kitten at home, large axillary and cervical lymph Bartonella henselae (cat scratch disease)
nodes
What is the best laboratory test to establish the Serologic test (indirect immunofluorescent
diagnosis of cat scratch disease assay)
Dog bite, 12 h later presents with swelling of the Pasteurella species
hand, tenderness, and erythema
Dog bite, 5 days later presents with swelling of the S. aureus
hand, tenderness, and erythema
Dog, cat, and human bite drug of choice Amoxicillin/clavulanate
Dog bite with severe complications, the patient is Ampicillin/sulbactam IV
hospitalized
Dog bite and allergic to penicillin Clindamycin and TMP-SMX
Bitten by a fox Give rabies vaccine and immunoglobulin
Dead bat found in the same room as the patient Give rabies vaccine and immunoglobulin
Bitten by a domestic dog during aggressive play Give amoxicillin/clavulanate
1056 O. I. Naga

The most common organism that causes infection Pasteurella multocida
in cat bite
Cochlear implants are associated with an increased Streptococcus pneumoniae
risk of which bacterial infection?
Child with perianal painful rash and rectal pain for Perianal bacterial dermatitis (caused by
3 days. O.E: bright red, sharply demarcated rash Streptococcus pyogenes or S. aureus),
around the anal area
What is the best empiric treatment in cases of Oral cephalexin or another antistaphylococcal
perianal bacterial dermatitis? antibiotic depends on the local pattern of
antibiotic resistance and sensitivity
A 5-year-old, fever, headache, pharyngeal S. pyogenes (group A streptococcus)
erythema, palatal petechiae, abdominal pain,
nausea
A 5-year-old presents with fever, headache, Scarlet fever
pharyngeal exudates, and diffuse sandpaper-like
rash. Gram-positive beta-hemolytic streptococci
isolated from throat culture
A 2-year-old child presents with low-grade fever, Streptococcosis (Streptococcus)
thick nasal discharge, and anterior cervical
lymphadenopathy
A 3-year-old, fever, runny nose, hoarse voice, Viral pharyngitis
cough, and pharyngeal exudates
A 12-year-old, throat pain with exudates, fever, Epstein–Barr virus (EBV) infectious
headache, large cervical lymph node, and mononucleosis
splenomegaly
Best screening test for suspected EBV infection in Monospot test
≥ 5-year-old
A football player is diagnosed with EBV without No contact sports for at least 4–6 weeks—
splenomegaly. How soon can he return to contact increased risk of splenic rupture
sports?
Abrupt onset of pharyngitis, palpebral Adenovirus infection (pharyngoconjunctival
conjunctivitis, fever, a moderate degree of illness, fever)
and preauricular lymphadenopathy, mild cough,
and nasal congestion, rhinorrhea, abdominal pain
Prodromal high fever and irritability, followed by Primary herpetic gingivostomatitis
painful vesicles that ulcerate on the anterior palate,
tongue, and buccal mucosa, with intensely inflamed
gingivae
A 6-year-old child with fever, headache, throat pain Rapid antigen Streptococcus testing (RAST). If
and abdominal pain. O/E: pharyngeal erythema, RAST is negative, obtain a throat culture.
palatal petechiae, and positive cervical Prescribing antibiotics for presumed group A
lymphadenopathy. What is the next best step? Streptococcus (GAS) without testing is not
appropriate

Poor feeding, drooling, tiny vesicles, and Herpangina (enteroviral stomatitis)
erythematous ulcers occur on the posterior pharynx,
involving the soft palate, uvula, and tonsillar
pillars, and resolve spontaneously within 1 week.
With or without fever
A painful 1- to 3-mm vesicles on an erythematous Hand-foot-mouth disease (enteroviral stomatitis
base involving the buccal mucosa, palate, tongue, with exanthem)
uvula, and anterior tonsillar pillars. A gray-white
vesicle surrounded by erythema primarily on the
palms and soles, also on the buttocks and distal
extremities
Throat pain, fever, grayish-white membrane on the Diphtheria
pharynx; the child is not immunized and looks
toxic
Child with a persistent tooth abscess developed Actinomycosis
multiple sinuses drainage on the cheeks with sulfur
granules seen in the exudates
A 12-year-old boy with a history of swimming in Leptospirosis
freshwater lagoons, developed headaches, myalgia,
and fever; 7 days later he became jaundiced, with
elevated creatinine level, high bilirubin level, mild
elevation of AST and ALT
Unimmunized, dirty wound, and fracture of the Tetanus vaccine and tetanus immunoglobulin
femur (TIG)
Immunizations up to date, last tetanus vaccine was No tetanus vaccine nor TIG
3 years ago, dirty wounds, and multiple compound
fractures in a car accident
A 12-year-old boy stepped on a dirty rusty nail, the Tdap immunization
last DTaP immunization was 8 years ago (received
5 doses of DTaP by the age 4 years of age)
A 12-year-old boy stepped on a clean object at Needs booster dose for pertussis component at
home, presents with a minor, clean wound 11–12 years (Tdap). Tetanus booster required
(received 5 doses of DTaP by the age 4 years of every 10 years
age)
Young adolescent works on an animal farm Anthrax
developed skin papule on the arm that eventually
ulcerates and forms black eschar with non-pitting,
painless induration and swelling
Unimmunized, presents with fever, muscle Poliomyelitis
weakness and paralysis involving the proximal
muscles first. History of foreign travel
A 2-month-old developed bronchiolitis and Human metapneumovirus
negative RSV
1058 O. I. Naga

Child sustained significant burn a few days ago, Start IV antibiotics
starts having a fever, tachypnea, tachycardia and
new discoloration of wound edges. What is the next
best step?
Central line, methicillin-resistant S. aureus Vancomycin
(MRSA) infection. What is the drug of choice?
IV vancomycin, suddenly develop a rash, itchiness, Red man syndrome (reduce IV infusion rate)
flushing, and tachycardia
Recently traveled to Africa, seizure, decreased level Plasmodium falciparum (cerebral malaria)
of consciousness, retinal hemorrhage, and
hypoglycemia. What is the most likely cause?
For travel to Africa, the prophylactic antimicrobial Atovaquone-proguanil or doxycycline
therapy of choice for malaria is (mefloquine has black box warning)
A 3-year-old developed osteomyelitis, culture is Kingella kingae (aerobic CO2 enhanced culture)
negative, not responding to vancomycin. What is
Neonate presents with fever, and blood culture Brain abscess
grows Citrobacter. What is the most common
complication?
The best study for neonates presenting with fever Brain CT or MRI
and Citrobacter bacteremia
Late-onset (7 days to 3 months of life) group B Bacteremia (more common), meningitis, or
streptococcal infection presents with osteomyelitis
Stiff neck, fever, CSF WBC < 1000, 80% Enterovirus PCR
neutrophil, negative CSF gram stain. What is the
best CSF study?
Empiric antibiotic therapy in a newborn with Ampicillin plus aminoglycoside or ampicillin
presumed bacterial meningitis plus cefotaxime
Empiric antibiotic therapy in infants and children Vancomycin plus ceftriaxone or cefotaxime
with presumed bacterial meningitis
What is the duration of therapy in most of the cases 14–21 days
of meningitis?
What are the long-term neurologic complications of Developmental delay, intellectual disability,
bacterial meningitis in children? hearing impairment, epilepsy, spasticity, and
hemiparesis
Child with tetralogy of Fallot presents with a S. aureus
headache, seizure and brain abscess
A 17-year-old female with a history of IV drug Endocarditis
abuse presents with fever, dyspnea, cough, chest
pain, tender subcutaneous nodules in the distal nail
pads, positive blood culture for S. aureus
Adolescent with high-risk behavior and IV drug Acute retroviral (HIV) syndrome
abuse presents with fever, lymphadenopathy,
pharyngitis, muscle and joint pain, mouth and
genital ulcers, skin rash including the palms and
soles, rapid strep and monospot tests are negative

The best initial test for the diagnosis of acute HIV DNA PCR
retroviral (HIV) syndrome Confirm with ELISA/Western blot and HIV
RNA PCR (viral load)
Main side effect of zidovudine (ZDV) Bone marrow suppression
A pregnant adolescent with HIV, her CD4 count is Start anti-HIV therapy immediately
800
Patient with HIV infection, diarrhea for 3 weeks Cryptosporidium
and not resolving
Child lives with his father who was in jail, Tuberculosis
developed cough, weight loss, night sweats, chest
radiograph shows hilar adenopathy and pneumonia
Developed large matted cervical lymph node, Mycobacterium avium
persistent for 6 weeks, and not responding to
antibiotic; you notice the overlying skin is
violaceous. Most likely diagnosis
Child presents with large anterior cervical lymph Surgical removal of the node with complete
node measure 7 × 4 cm, matted, painless, PPD is excision (atypical mycobacteria, including M.
9 mm induration, not responding to antibiotics for avium)
9 weeks
First-line treatment for head lice Pyrethrin and 1% permethrin
When can children with head lice infestation return Should be allowed to complete the school day
to school or daycare? (no exclusion from school or daycare because
of head lice or nits in healthy children)
Head lice resistant after the treatment with Give malathion (ovicidal)
permethrin
A 1-month-old with scabies. What is the drug of Precipitated sulfur 6% in petrolatum
choice?
A young girl with malodorous vaginal discharge. Retained foreign body
She has a vaginal discharge visible at the introitus.
Mother denied sexual abuse or trauma. What is the
most likely cause?
Adolescent girl presents with severe rash and Toxic shock syndrome due to Staphylococcus
desquamation in the hands and feet, hypotension, Treatment: IV vancomycin + clindamycin)
and fever. The vaginal examination reveals a
tampon
A 7-year-old presents with fever, malaise, skin rash Staphylococcal scalded skin syndrome
with bullae, and positive Nikolsky sign
A 2-week-old neonate with a history of a PICC Enterococcus faecium—resistant to vancomycin
line, with fever, bacteremia, and positive culture (VRE) and cephalosporins
showing gram-positive cocci Treatment: linezolid
A 13-year-old presents with bloody diarrhea, Clostridium difficile—initial treatment choice
abdominal pain and cramps; patient recently treated for first, and a non-severe episode is oral
with clindamycin metronidazole
Patient does not respond to metronidazole and is Oral vancomycin
diagnosed with another episode of C. difficile. What
antibiotic should be used?
1060 O. I. Naga

Child with a fever, cervical lymphadenopathy. Toxoplasmosis
Child ingested undercooked meat. CT scan shows
ring enhanced lesion
HEMATOLOGY/ONCOLOGY
Nora E. Rahmani and Arpan A. Sinha
Last-Minute Review—Hematology/Oncology Most Likely Answer

Low hemoglobin, low mean corpuscular volume Iron deficiency anemia
(MCV), low iron, low transferrin saturation, low
ferritin, high red cell distribution width (RDW),
Mentzer index (MCV/RBCs) > 13 and high total
iron-binding capacity (TIBC)
Low hemoglobin, low iron, low/normal TIBC, Anemia of chronic disease
normal/high ferritin level
Mild anemia, low MCV, normal iron, normal TIBC, Thalassemia trait
normal ferritin, normal RDW, Mentzer index < 13
Mild anemia, low MCV, normal iron, normal TIBC, Alpha thalassemia trait
normal ferritin, normal RDW, Mentzer index < 13,
and normal electrophoresis (no elevated Hgb A2)
A 12-month-old boy adopted from China with Beta thalassemia major. (Alpha thalassemia
delayed growth, hepatosplenomegaly, jaundice, and major leads to severe anemia and hydrops
“chipmunk facies” fetalis in utero, typically incompatible with life
without treatment)
Electrophoresis result showed: Hb A > 98% with a Normal electrophoresis
small amount of Hb A2 visible
Electrophoresis of a 3-year-old child, result Beta thalassemia minor
showed: Hb A is decreased to 94%, Hb A2 is
increased at 5%, and Hb F is 1%
After birth, hemoglobin electrophoresis result Beta thalassemia major
showed: No Hb A, Hb A2 of 4%, Hb F of 96%. No
other abnormal hemoglobins seen
A 2-month-old premature infant has a Hgb 9.0 with Anemia of prematurity
normal MCV
How much will 10 mL/kg of packed RBCs raise the ~2 g/dL
hemoglobin?
Excessive cow milk consumption (> 16 oz/day) and Iron deficiency anemia
microcytic anemia
What are the best initial laboratory tests in cases CBC and reticulocyte count
with suspected iron deficiency anemia?
What is the best indicator of response to iron An increase in hemoglobin, reticulocyte count,
therapy? and MCV within 1–4 weeks
How long should iron therapy continue in cases of At least 1–2 months after anemia has been
iron deficiency anemia? corrected to replete iron stores

What is the classic dose of iron in cases of iron 3–6 mg/kg/day of “elemental iron”
deficiency anemia?
A 2-year-old infant with a hemoglobin of 4 g/dL, Transient erythroblastopenia of childhood
normal MCV, low reticulocyte count, normal ADA
(adenosine deaminase activity), negative direct
Coombs test and no signs of hemolysis
A 7-year-old child presents with pancytopenia, on Fanconi anemia
exam also noted to have hypoplastic thumb and
radius, hyperpigmentation, and abnormal facies
A 4-month-old infant with severe anemia, high Diamond–Blackfan anemia
MCV (macrocytic), elevated ADA, and exam shows
triphalangeal thumb
Macrocytic anemia, neutropenia, Pearson marrow-pancreas syndrome
thrombocytopenia, exocrine pancreatic
insufficiency, ring sideroblasts in the bone marrow
Short stature, imperforate anus, hypoplastic teeth, Shwachman–Diamond syndrome
frequent infections, macrocytic anemia,
neutropenia, thrombocytopenia, and exocrine
pancreatic insufficiency
Child who consumes goat’s milk and has Folic acid deficiency
macrocytic anemia
Child whose family is strictly vegan and has Suspect B12 deficiency. Supplement with B12
macrocytic anemia
Child with macrocytic anemia, glossitis, abdominal Pernicious anemia (B12 deficiency due to IF
pain, gait instability with positive anti-IF antibodies antibodies)
Child with pallor, increased jaundice, Hereditary spherocytosis
splenomegaly, reticulocytosis, and normocytic
hemolytic anemia. Peripheral smear shows RBCs
without central pallor
An African-American boy recently started on G6PD deficiency. Enzyme activity test is
Bactrim for UTI with sudden onset of dark urine, usually normal (false negative) during active
jaundice, and pallor. Splenomegaly on the exam. hemolysis due to the destruction of older
Labs are notable for anemia, reticulocytosis, erythrocytes (that are G6PD deficient) and
indirect hyperbilirubinemia, low haptoglobin, and presence of younger erythrocytes and
normal G6PD enzyme activity (during the episode). reticulocytes (that have normal/near-normal
Peripheral smear is positive for Heinz bodies enzyme activity). The test should be repeated
during remission, not during active hemolysis
Fava beans, primaquine, sulfa drugs, and G6PD deficiency
nitrofurantoin are known to exacerbate which
condition?
Sickle cell anemia, swollen hands and feet, severe Dactylitis
pain in hands and feet
The most common cause of sepsis in patients with Streptococcus pneumoniae
sickle cell disease
Child with sickle cell disease presents with severe Splenic sequestration
anemia, reticulocytosis, thrombocytopenia, and Next best step → transfusion of packed RBCs
rapidly enlarging spleen (monitor hemoglobin, expect additional rise in
Hgb from auto-transfusion from spleen)
1062 O. I. Naga

Child with sickle cell disease, fever, malaise, rash, Aplastic crisis → treatment packed RBCs
severe anemia, and reticulocytopenia transfusion as needed
Which virus is the most common cause of aplastic Parvovirus B19
crisis?
Common causes of morbidity and mortality in Infection, acute chest syndrome, stroke
children with sickle cell disease
Child with sickle cell anemia presents with fever, Acute chest syndrome—start ceftriaxone +
chest pain, tachypnea, shortness of breath, and new macrolide (to cover for atypical organisms).
pulmonary infiltrate on imaging. Management? Avoid overhydration
Sickle cell patients are at higher risk of which type Encapsulated organisms—due to functional
of organisms? asplenia. Make sure vaccines are up to date
What is the most common reason for Vaso-occlusive pain crisis
hospitalization in the child with sickle cell anemia? Treatment: IV hydration, NSAIDs, and opioids
Management?
Adolescent male with a painful erection that has Prolonged priapism—needs emergent
lasted for several hours. Management? evaluation and treatment. Ask patient to come to
the ER, aspiration +/− irrigation,
phenylephrine, pain control, possible surgical
management
What is the most common cause of osteomyelitis in Salmonella
a child with sickle cell disease?
What is the next best step in a child with sickle cell Imaging studies (MRI), blood culture,
disease and suspected osteomyelitis? antibiotics (cover Salmonella and other Gram-
negative bacilli, as well as S. aureus), consider
biopsy for culture
Adolescent with sudden onset of fatigue, pallor, Autoimmune hemolytic anemia (AIHA)
scleral icterus, and tachycardia, high reticulocyte
count, positive direct antibody test. What is the
most likely diagnosis?
What is the next best step in the previous life- Start steroids. Supportive care may include
threatening case of autoimmune hemolytic anemia transfusion of the least incompatible packed
(AIHA)? RBC unit(s)
Fever and absolute neutrophil count (ANC) < 500. Admit to the hospital, blood culture, IV
What is the next best step? antibiotics
Neutropenia for 1 week every 3 weeks, associated Cyclic neutropenia
with gingivitis, pharyngitis, skin infections during
nadir
How to establish the diagnosis of cyclic CBC 2–3 times per week for 6–8 weeks
neutropenia?
What is the best management of cyclic Prophylactic granulocyte-colony stimulating
neutropenia? factor (G-CSF). Immediate attention with fevers
Severe neutropenia from birth, oral ulcers, Kostmann syndrome
gingivitis, recurrent infections, ANC is low all the
time
Persistent neck lymphadenopathy more than 1 cm, Referral to a pediatric oncologist (lymph node
fever, weight loss, night sweats, lack of response to biopsy)
oral antibiotics

Child with a supraclavicular lymph node for Referral to a pediatric oncologist (must be
2 weeks. No other symptoms biopsied or investigated)
Most common malignancy in infants Neuroblastoma
Most common malignancy in childhood Acute lymphocytic leukemia
Most common CNS tumor in children Astrocytoma
Most common benign tumor of the liver in children Infantile hemangioendothelioma (most
commonly occurs in the first 6 months of life,
rarely seen in children > 3 years of age)
Toddler with an abdominal mass, ecchymosis, Neuroblastoma
raccoon eye, myoclonic jerking, and random eye
movements. The abdominal US is positive for a
large suprarenal mass. Urine catecholamines are
elevated (HVA and VMA )
Child presents with gingivitis, hepatosplenomegaly, Acute myelogenous leukemia
orbital chloromas, WBC > 100,000. Peripheral
smear shows Auer rods in blasts
Chronic myelogenous leukemia is associated with Philadelphia chromosome t(9:22)
which chromosome translocation?
A 1-year-old with very large spleen, moderate Juvenile myelomonocytic leukemia (JMML).
leukocytosis (increased monocytes), xanthoma, JMML has an association with NF1 and
eczema, and café-au-lait spots Noonan syndrome
Child with an abdominal mass presents with Burkitt lymphoma (tumor lysis syndrome)
abdominal pain, weakness, lethargy, oliguria,
edema, elevated lactate dehydrogenase (LDH) and
uric acid, hyperkalemia, elevated phosphate, and
low calcium
What is the next best step in the previous case of Transfer immediately to oncology unit or PICU
tumor lysis syndrome? for supportive care, including hydration,
correction of electrolytes—hyperkalemia,
hyperphosphatemia, hyperuricemia, renal
dysfunction. May even require hemodialysis
Microscopic picture of Hodgkin lymphoma Reed-Sternberg cell
The most common type of lymphoma in children Non-Hodgkin lymphoma
Most common malignant tumor of the kidney in Wilms tumor
children
Child with macroglossia and Wilms tumor Beckwith–Wiedemann syndrome
Most common soft-tissue tumor in children Rhabdomyosarcoma
Long-term complications of radiotherapy Growth retardation, hypothyroidism, early onset
coronary artery disease, pulmonary fibrosis,
secondary malignancy
Complication of doxorubicin therapy Cardiomyopathy
Complication of vincristine therapy Neuropathy
This antineoplastic drug can cause renal Cisplatin
impairment and ototoxicity
Complication of methotrexate therapy Renal and liver toxicity
Complication of cyclophosphamide therapy Hemorrhagic cystitis
1064 O. I. Naga

Common electrolyte abnormalities in tumor lysis Hyperkalemia, hyperuricemia,
syndrome? hyperphosphatemia, and hypocalcemia
A 12-year-old boy with pain and swelling above the Osteosarcoma
knee, pain is worse at night; radiograph shows a
bone lesion with Codman’s triangle and sunburst
pattern
A 16-year-old girl with back pain and limp, fever, Ewing sarcoma
weight loss, radiograph shows a mass on the iliac
bone with a lytic lesion, onion-skin appearance
The translocation is commonly seen in patients t (11;22)
with Ewing sarcoma
Child with a painless, bony mass on the knee, Osteochondroma
radiograph shows broad base projection
Child with persistent pain in the lower part of the Osteoid osteoma
right femur, radiograph shows metaphyseal lucency
surrounded by sclerotic bone, NSAIDs relieve the
pain
Hemangioblastoma, pheochromocytoma, renal cell Von–Hippel–Lindau disease
carcinoma, pancreatic cyst, and café-a- lait spots
Impaired upward gaze, mid-dilated pupil, Parinaud syndrome
nystagmus, and lid retraction
New-onset head tilt or torticollis, early morning Posterior fossa brain tumor, e.g.,
vomiting, headache, and gait disturbance medulloblastoma
Most common malignant CNS tumor in children Medulloblastoma
Most common CNS tumor Low-grade glioma (pilocytic astrocytoma is the
most common LGG)
Brain tumor with the best survival rate in children Pilocytic astrocytoma
Child with recurrent headaches, growth failure, Craniopharyngioma
polydipsia, double vision
A 6-month-old child with strabismus, absent red Retinoblastoma
reflex, and leukocoria
The liver tumor that is associated with prematurity Hepatoblastoma
The tumor that is associated with cryptorchidism Gonadoblastoma
An infant with intracranial hemorrhage, Factor XIII deficiency
prothrombin time (PT), partial thromboplastin time
(PTT), and platelet count, fibrinogen and vWD
panel is within normal limits
Child with normal PT, very prolonged PTT, has no Factor XII deficiency
history of excessive bleeding even after injuries
A 5-year-old with upper respiratory tract infection Idiopathic thrombocytopenic purpura (ITP)
2 weeks ago, presents with a bloody nose, petechial
rash all over the body and oral mucosa. CBC is
normal except platelet count is 12,000, peripheral
smear shows very few large platelets
What is the treatment in the previous case of ITP? Observation if no signs of bleeding; if signs of
bleeding, then treat with IVIG or steroids

A 2-year-old boy with recurrent infections, eczema, Wiskott–Aldrich syndrome
severe thrombocytopenia, and small platelets
Newborn with severe thrombocytopenia, maternal Neonatal ITP → give IVIG
history of ITP or other autoimmune disorder
Newborn with severe thrombocytopenia, maternal Neonatal alloimmune thrombocytopenia →
history of prior children with neonatal transfuse maternal platelets (gold standard);
thrombocytopenia and no maternal history of however, difficult to obtain. The alternative
autoimmunity option is donor platelets +/− IVIG, steroids
Unusual bleeding since birth, recurrent bruising, Platelet function disorders, e.g., Bernard–
recurrent mucosal bleeding, low to normal platelet Soulier syndrome, Glanzmann thrombasthenia
count, normal PT and PTT, normal fibrinogen,
normal von Willebrand antigen and activity
A 10-year-old with recurrent epistaxis, easy Glanzmann thrombasthenia (normal platelet
bruising, gingival bleeding, normal count and count and size)
morphology of platelets, platelets agglutinate to
ristocetin, poor platelet aggregation with adenosine
diphosphate (ADP), epinephrine, and collagen
A 10-year-old with a suspected bleeding disorder, Bernard–Soulier syndrome (large platelets, can
workup shows mild thrombocytopenia, with large have low platelet count)
abnormal platelets, platelets do not agglutinate to
ristocetin but agglutinate to ADP, epinephrine, and
collagen
Most appropriate management for life-threatening Infusion of platelets with normal function
bleeding in a child with a known or suspected
platelet function disorder
A 48-h-old newborn presents with prolonged Thrombocytopenia with absent radii (TAR
bleeding after circumcision, CBC shows severe syndrome)
thrombocytopenia. On exam no radii in both
forearms but with normal thumbs
Male newborn with prolonged bleeding after Factor VIII or IX deficiency, or hemophilia A or
circumcision, and prolonged PTT B
A 15-year-old girl with excessive menstrual Von Willebrand disease
bleeding every month since menarche, normal PT
and PTT, decrease in biological activity of
ristocetin cofactor assay (rCoF)
A 4-year-old child with a recent history of vomiting
Hemolytic uremic syndrome—occurs in infants
and bloody diarrhea found to have and children after prodromal diarrhea,
thrombocytopenia, elevated BUN and creatinine, associated with bacteria particularly E. coli
schistocytes on peripheral smear O157: H7, and Shigella dysenteriae
Child currently hospitalized in the PICU with Disseminated intravascular coagulation (DIC)
prolonged PT, PTT, elevated D-dimer, Treatment: treat the underlying cause (e.g.,
thrombocytopenia, and decreased fibrinogen antibiotics for sepsis). Supportive care with
blood products—FFP +/− cryoprecipitate
A 17-year-old Caucasian boy with recurrent Factor V Leiden mutation—resistance to
episodes of DVT along with a strong family history activated protein C
of DVT
1066 O. I. Naga

A 2-year-old boy with oral ulcers, cradle cap-like Langerhans cell histiocytosis—Birbeck
rash, and gingivitis, with radiograph showing lytic granules on electron microscopy
lesions in the skull
A 1-year-old sick-appearing child with fever, Hemophagocytic lymphohistiocytosis (HLH)
hepatosplenomegaly, pancytopenia,
hypertriglyceridemia, and very elevated ferritin;
presence of hemophagocytosis in bone marrow
ALLERGY AND IMMUNOLOGY
Last-Minute Review—Allergy and Immunology Most Likely Answer

Antibody that has a major role in allergic IgE
conditions, e.g., anaphylaxis, atopy, asthma,
allergic rhinitis, food allergies
Antibody that mediates type I hypersensitivity IgE
reaction
First antibody produced in an infection IgM
An antibody found in body mucosal secretions IgA
What is the prevalence of atopic disorders in Up to 60%
children with one affected parent?
What is the prevalence of atopic disorders in Up to 80% (family history is critical in all atopic
children with 2 affected parents? disorders)
What are atopic disorders? Atopic dermatitis, asthma, allergic rhinitis, and
food allergies
What are the indications of allergy testing? Significant allergies, e.g., asthma, anaphylaxis,
food or drug allergies, difficult to treat allergies
or requirement for specific treatment
An infant with severe eczema and/or severe egg Evaluate for peanut reactivity with either skin-
allergy prick testing and/or serum IgE levels, and if
necessary, oral food challenge
Which allergy test is preferred in cases of Radioallergosorbent test (RAST) (allergen-
dermatographism, generalized dermatitis, or a specific IgE antibody)
clinical history of severe anaphylactic reactions to
a given food?
Which allergy test is associated with a high false Both skin-prick testing and serum IgE levels
positive rate?
Child currently on diphenhydramine for allergies is At least 5 days prior to testing
scheduled for skin allergy testing. When should
diphenhydramine be stopped?
Child currently on cetirizine for allergies is At least 7 days prior to testing
scheduled for skin allergy testing. When should
cetirizine be stopped?

Child currently on amitriptyline for migraine At least 2 weeks prior to testing
headache prophylaxis is scheduled for skin allergy
testing. When should amitriptyline be stopped?
What is the first step that should be taken in the Avoidance or reduction of allergen exposures
management of allergic rhinitis?
The first-line pharmacologic treatment of allergic Intranasal steroids and/or second-generation oral
rhinitis antihistamines
Common complications of untreated allergic Recurrent acute otitis media, sinusitis, chronic
rhinitis cough, and asthma
Complications of prolonged use of nasal Rhinitis medicamentosa
adrenergic drops
An 8-year-old male presents with congestion, itchy Avoid the trigger (e.g., by keeping the cat at
nose, and watery eyes. Symptoms are exacerbated least outside the bedroom or the house all the
when playing with the pet cat. He loves his cat. time; HEPA filters can help)
What is the most effective treatment?
Child with a history of pollen allergy develops Oral allergy syndrome (OAS) (cross-reactivity
rapid onset of itching, swelling of the lips, mouth, with pollen)
and throat when eating raw fruits and vegetables.
What is the most likely cause?
What is the best treatment for OAS? Avoid offending foods
How long do the allergies to peanuts, tree nuts, Lifelong allergies
seafood, and fish last?
How long do the allergies to milk, eggs, and soy Most children outgrow by 5 years of age
last?
A 2-month-old exclusively breastfed infant is seen Reassurance (counsel mother to avoid dairy, soy,
for bloody stools; weight gain is appropriate, and eggs for 2 weeks, then re-evaluate)
physical exam is normal
Induration reaction to TB testing after 72 h is an Type IV: cell-mediated hypersensitivity
example of
Allergy to contrast media is an example of Non-IgE mediated
Child with a history of severe allergic reaction to Administer prednisone and diphenhydramine
radiographic contrast media is going for CT scan before injection or choose other alternative
with IV contrast imaging tests
Child with a history of severe allergic reaction to No (iodine allergy is not a risk factor for
seafood is going for an abdominal CT scan with allergic-type contrast reactions)
oral and IV contrast. Does he or she need a
pretreatment with prednisone and
diphenhydramine?
A 16-year-old male with a new watch notices an Type 4—contact dermatitis, a delayed
area of erythema located on the wrist where the hypersensitivity reaction
watch was worn. No other lesions
What is the best treatment in cases of contact Avoid offending agents
dermatitis?
Child received penicillin 10 days ago for the first Serum sickness
time, presents with fever, nausea, vomiting, pruritic
skin rash (urticaria), angioedema, joint pain,
lymphadenopathy, myalgia, and proteinuria
1068 O. I. Naga

A common trigger of allergic reactions in a patient Latex
with spina bifida or congenital urogenital problems
What is the most common specific autoimmune Autoimmune thyroid disease (laboratory
association with chronic urticaria? evaluation should include thyroid-stimulating
hormone (TSH) level and thyroid antibodies)
Sudden onset of lip swelling, abdominal pain, Hereditary angioedema
swelling of both feet, non-pruritic erythematous
skin rash; one family member has the same
condition
What is the cause of hereditary angioedema Low levels or decreased function of plasma
(HAE)? protein C1 inhibitor (C1-INH). (Autosomal
dominant)
Initial screening test for a patient with suspected C4 level most reliable and cost-effective
hereditary angioedema screening test for HAE
The test that can differentiate between various C1-INH functional assay
types of hereditary angioedema
A 6-year-old male with yellow-tan macules located Mastocytosis—Darier sign: urticaria after
on the upper extremities. Parents notice localized stroking lesions
erythema following scratching of the lesions and
after taking a hot shower
Common diagnostic lab for mastocytosis Elevated tryptase levels
A 15-year-old male presents with several Exercise-induced urticaria
erythematous, pruritic circumscribed lesions that
occur with exercise
Child presents a few minutes after eating peanut IM epinephrine to administer as quickly as
butter with urticaria, skin flushing, pruritus, possible
angioedema, rhinorrhea, wheezing, shortness of
breath, abdominal pain, vomiting, diarrhea, light-
headedness. What is the next best step?
Child with a history of life-threatening reaction to Referral to an allergist for immunotherapy
a bee sting is coming to your office for a follow-up
after he was discharged from the ER with EpiPen
prescription. What is the next best step?
A 4-year-old male scheduled for a well child All vaccines including MMR and varicella
check; he was recently treated with a 5-day course
of oral steroids for asthma exacerbation. Which
vaccines can be given?
A 4-year-old male scheduled for a well child No—patients receiving high steroids for greater
check; he has been treated with high dose steroids than 2 weeks should be off steroids for at least
for 4 weeks. Should the MMR and varicella 1 month
vaccines be given?
Child is being treated with intranasal steroids for Yes
allergic rhinitis. Should the MMR and varicella
vaccines be given?
What is the best initial test for any child with Complete blood count (CBC)
suspected immunodeficiency?

Patient with recurrent meningococcal meningitis The defect in terminal complement C5–C9
deficiency
Initial screening test for a patient with suspected (CH50) test
complement deficiency, e.g., recurrent (Neisseria
meningitidis) meningitis
Complement deficiency that increases the risk of C2 deficiency
systemic lupus erythematosus
What is the best screening test for cell-mediated T-cell phenotyping (CD4/CD8, memory vs.
immunity associated with T-cell defects? naïve T cells) and T-cell proliferative responses
What is the best initial test for an infant with Immunoglobulin levels
suspected humoral immune deficiency?
An 8-week-old boy presents with diarrhea, Severe combined immunodeficiency (SCID)
pneumonia, persistent oral thrush, eczematous-like
skin lesions, sepsis, lymphopenia, and failure to
thrive
The enzyme deficiency that is found in SCID? Adenosine deaminase deficiency
A 9-month-old boy, previously healthy, presents X-linked agammaglobulinemia (usually starts
with recurrent otitis media, 2 episodes of after first 6 months of life)
pneumonia in the last 2 months, persistent
giardiasis. O/E: the lymph nodes, the tonsils are
absent
Adolescent presents with recurrent sinus and Common variable immunodeficiency
pulmonary infections due to encapsulated bacteria,
malabsorption, hepatosplenomegaly, and low level
of immunoglobulins (IgG, IgM, and IgA)
The best treatment for a child with asymptomatic Observation (no treatment is necessary)
transient hypogammaglobulinemia of infancy
An 8-year-old boy presents with eczema, recurrent Job syndrome (autosomal dominant hyper-IgE
Staphylococcus aureus skin infections without syndrome)
inflammatory response “cold abscess,”
pneumatoceles, coarse facial features, eosinophilia,
and IgE level is 80,000 IU
A 5-month-old presents with Pneumocystis jiroveci X-linked hyper IgM syndrome
pneumonia, mouth ulcers, severe neutropenia,
recurrent sinusitis, otitis media, chronic diarrhea,
failure to thrive, and negative HIV
A 4-year-old boy with recurrent skin abscesses, Chronic granulomatous disease (X-linked)
spleen and liver abscesses, and osteomyelitis
Test of choice in a patient with a suspected chronic DHR oxidation is preferred, NBT reduction can
granulomatous disease be used
Severe progressive infectious mononucleosis and X-linked lymphoproliferative syndrome (Duncan
Epstein–Barr virus (EBV) fulminant hepatitis syndrome)
Highly elevated WBC in a 10-week-old infant who Leukocyte adhesion defect type I
still has an umbilical cord
Test of choice in a patient with suspected leukocyte Flow cytometry beta 2 integrin CD11b/CD18 on
adhesion defect leukocytes
1070 O. I. Naga

Newborn with hypocalcemia, tetralogy of Fallot, DiGeorge anomaly (deletion of chromosome
interrupted aortic arch, and abnormal facial 22q11.2)
features
Recurrent ear infections, eczema, profuse bleeding Wiskott–Aldrich syndrome
during a circumcision procedure,
thrombocytopenia, and small platelets
Persistent thrush, nail dystrophy, and Chronic mucocutaneous candidiasis
endocrinopathies
Short stature, fine hair, and severe varicella Cartilage-hair hypoplasia with short-limbed
infection dwarfism
Oculocutaneous albinism, recurrent infections, and Chédiak–Higashi syndrome
easy bruising
Candidiasis with raw egg ingestion Biotin-dependent carboxylases deficiency
A 4-year-old with short stature, micrognathia, Bloom syndrome
telangiectasia, immunodeficiency, learning
disability, deficiency of DNA ligase I
An 8-year-old boy presents with recurrent ear and Ataxia–telangiectasia (autosomal recessive)
sinus infections, ataxia, oculocutaneous
telangiectasia, and elevated α1-fetoprotein
ENDOCRINOLOGY
Amr Morsi
Last-Minute Review—Endocrinology Most Likely Answer

What is the first sign of puberty in a boy? Testicular enlargement
What is the first sign of puberty in a girl? Breast budding
The height acceleration peaks in girls is at which Between stage 2 and 3 SMR
sexual maturation rating (SMR) stage?
The height acceleration peaks in boys is at which Between stage 4 and 5 SMR
SMR stage?
How many years after breast development does 2.5 years (approximately)
menarche start?
A 5-year-old female, pubic hair, adult odor, no Premature adrenarche
breast development, bone age is equal to
chronological age, slightly increased
dehydroepiandrosterone (DHEA) level, normal
growth pattern for age
A 2-year-old female with bilateral breast buds, Benign premature thelarche
unchanged for 1 year, no growth acceleration
A 4-year-old female with new-onset bilateral Central precocious puberty is very likely
breast enlargement, advanced bone age, and
elevated luteinizing hormone (LH) and follicle-
stimulating hormone (FSH)

A 4-year-old boy presents with an adult-size Peripheral precocious puberty
phallus, pubic and axillary hair, acne, well-defined
muscle tone, prepubertal size testicles
A 4-year-old boy presents with an adult-size Central precocious puberty
phallus, pubic and axillary hair, acne, well-defined
muscle tone, pubertal size testicles, advanced bone
age
A 4-year old boy with new-onset adult body odor, Brain MRI
recent growth acceleration, pubic and axillary hair,
thinning of the scrotum, enlargement of both
testicles. Elevated LH and FSH. What is the best
study to establish the diagnosis?
A 5-year-old girl with pubic hair, mild Simple virilizing CAH-21 OH deficiency
hyperpigmentation of skin folds, slightly enlarged
clitoris
Second newborn screen positive for high Repeat 17-hydroxyprogesterone test
17-hydroxyprogesterone. What is the next best
step?
Newborn with proximal hypospadias (e.g., Ultrasonography for internal genitalia,
penoscrotal) and cryptorchidism karyotype, and serum electrolytes to screen for
congenital adrenal hyperplasia
What is the best treatment of congenital adrenal Hydrocortisone and fludrocortisone
hyperplasia?
What is the treatment for a patient with congenital IV hydrocortisone and IV fluid hydration
adrenal hyperplasia who presents with vomiting
and low blood pressure?
A 2-week-old male with failure to thrive, persistent CAH 21-OH deficiency (pyloric stenosis is
vomiting, dehydration, acidosis associated with metabolic alkalosis)
Ambiguous genitalia, nephropathy, Wilms tumor, Denys–Drash syndrome
renal failure by 3 years of age
Female phenotype at birth with undifferentiated Swyer syndrome (XY pure gonadal dysgenesis)
streak gonads, presence of vagina/fallopian tubes,
at puberty no breast development/menstruation,
development of gonadoblastoma is the highest risk
Newborn with a small penis, bifid scrotum, 5-alpha reductase deficiency (autosomal
urogenital sinus, blind vaginal pouch, testes are in recessive)
the inguinal canal, raised as a female, virilization
occurs at the time of puberty, enlargement of penis
and scrotum, sperm formation, and normal adult
height
Infant phenotypically female at birth, raised as Androgen insensitivity syndrome; 46, XY
female, vagina ends in a blind pouch, no uterus, no (X-linked recessive disorder)
fallopian tubes, intra-abdominal testes, normal
breast development, no menses, normal male adult
height, testosterone level is normal
1072 O. I. Naga

XY normal male phenotype, inguinal hernia, Persistent Müllerian duct syndrome
undescended testis, Müllerian structures found
incidentally (uterus and fallopian tubes)
A 4-year-old with precocious puberty, large café- McCune–Albright syndrome
au-lait spots, skeletal fibrous dysplasia, and
vaginal bleeding are associated with
A slow growth rate in the first 2 years of life Constitutional growth delay
(< third percentile), growth velocity afterward is
5.5 cm/year, delayed bone age, delayed puberty,
father was a late bloomer
Short child, growth velocity is 5 cm/year. Bone age Genetic/familial short stature
is consistent with chronological age, father and
mother are short
A 4-year-old, height < 3rd percentile, growth Growth hormone deficiency
velocity is less than 5 cm/year, microphallus
Common hormone deficiency associated with Growth hormone deficiency
single maxillary central incisors, septo-optic
dysplasia, cleft lip, cleft palate, and microphallus
Normal length and weight by birth initially that Congenital growth hormone deficiency
drops by 1-year, conjugated hyperbilirubinemia,
hypoglycemia, broad facies, and microphallus
Decreased levels of IGF-1 and IGF-BP3 are seen Growth hormone deficiency
in which hormone deficiency?
Normal growth hormone levels, height < 2.25 SD Idiopathic short stature
below mean for age, otherwise normal healthy
child
How do you calculate the mid-parental height for a [Mother height + Father height +13 cm]/2
male?
How do you calculate the mid-parental height for a [Mother height + Father height—13 cm]/2
female?
Pseudotumor cerebri, slipped capital femoral Growth hormone
epiphysis, and gynecomastia are the possible side
effects of which hormonal therapy
A 7-year-old boy with a progressive headache, Brain MRI (craniopharyngioma)
vomiting without nausea, bitemporal hemianopsia,
short stature, weight gain, and fatigue. What is the
next best step?
A 7-year-old boy, at birth, was large for gestational Cerebral gigantism (Soto syndrome)
age, macrocephaly, a rapid growth rate in the first
3 years of life; now presenting with cognitive
deficiency, autistic behavior, attention deficit
hyperactivity disorder (ADHD), large and
protruded head, large hands and feet, hypotonia,
clumsiness, advanced bone age

Boy with hypoplasia of optic nerves, nystagmus, Septo-optic dysplasia (De Morsier syndrome)
an absence of septum pellucidum, schizencephaly,
seizures, hypopituitarism, presented with
hypoglycemia, jaundice, and micropenis at birth
A 17-year-old female, amenorrhea, headache, Prolactinoma (macroadenoma)
galactorrhea, visual field defect; the pregnancy test
is negative, and serum prolactin is > 200 mg/
dL. MRI showed a pituitary mass of 15 mm with
encroachment on the optic chiasm
A 17-year-old boy, no signs of puberty, penis, and Kallmann syndrome (hypogonadotropic
testicles are prepubertal, and anosmia hypogonadism)
A 17-year-old male presents for a well visit. He Klinefelter syndrome 47, XXY karyotype
has academic difficulty, gynecomastia, small firm
testicles (< 10 mL). He is tall with
disproportionately long legs and arms
A 16-year-old female, short stature (< third Turner syndrome; 45, X karyotype
percentile), no breast development, amenorrhea,
low hairline, shield-shaped chest, spooning of her
fingernails, cubitus valgus, and sensorineural
hearing loss
The most common cardiac defect associated with Bicuspid aortic valve
Turner syndrome
Newborn girl had cystic hygroma on fetal Turner syndrome; 45, X karyotype
ultrasound, lymphedema of the feet, webbed neck,
heart murmur, and horseshoe kidney
A 5-year-old male, lymphedema of the feet at Noonan syndrome (mutations in the RAS-
birth, short stature, webbed neck, strabismus, MAPK pathway)
hearing loss, joint laxity, pulmonary stenosis,
intellectual disability, normal karyotype
Newborn screen of a 6-day-old boy showed Obtain confirmatory TSH and free thyroxine
abnormal thyroid-stimulating hormone (TSH) level now but initiate the treatment immediately,
of 230 mIU/L (elevated TSH > 40 mIU/L). before the results of the confirmatory tests are
Physical examination is unremarkable. What is the available
next best step?
What is the optimal care of neonates with Early diagnosis before age 10–13 days and
congenital hypothyroidism? normalization of thyroid hormone blood levels
by age 3 weeks
The most common cause of congenital Thyroid dysgenesis
hypothyroidism
What is the treatment of congenital Levothyroxine tablet (initial dose is 10–15 mcg/
hypothyroidism and how should the treatment be kg/day) should be crushed and mixed with breast
given? milk or formula (cannot be mixed with soy
formula)
Low free T4, elevated TSH Primary hypothyroidism
Low free T4, normal or low TSH Central hypothyroidism
High free T4 and T3, low TSH Hyperthyroidism (most common)
1074 O. I. Naga

Normal or low free T4, high T3, low TSH Hyperthyroidism (less common)
Normal T4, low T3, normal/low TSH, the patient Euthyroid sick syndrome
has pneumonia
Low total T4, normal free T4, normal TSH Thyroxine-binding globulin deficiency (TBG),
hypoproteinemia, e.g., malnutrition and
nephrotic syndrome
A 11-year-old female with no growth for 2 years, Hypothyroidism (likely Hashimoto)
tired, constipated and “yellowish” skin
Adolescent with thyroid enlargement, no Hashimoto thyroiditis
symptoms, TSH and free T4 are within the
reference range, positive antithyroid peroxidase
(TPO)
A 14-year-old girl, school troubles, getting in Graves disease (hyperthyroidism)
fights, appears to be on drugs because of red bulgy
eyes and irritability
What is the best test to confirm the diagnosis of Thyrotropin receptor-stimulating
Graves disease? immunoglobulin (TSI)
A painful thyroid gland that started after viral De Quervain thyroiditis—initial hyperthyroid
infection associated with elevated ESR with an phase, then hypothyroid phase with eventual
eventual return to normal thyroid function recovery
Newborn child with tachycardia, irritability, Neonatal thyrotoxicosis
hypertension, mother with a history of Graves
disease?
The most common symptom of hyperthyroidism or Weakness/fatigue
Graves disease
The most common side effect of antithyroid drugs Transient urticarial rash
(e.g., methimazole)
The best diagnostic test for solitary thyroid nodule Fine needle aspiration biopsy; US-guided
The most common thyroid cancer in pediatric Well-differentiated thyroid (follicular/papillary)
patients carcinoma
Medullary thyroid cancer, hyperparathyroidism, Multiple endocrine neoplasia (MEN)-2A
pheochromocytoma
Medullary thyroid cancer, pheochromocytoma, MEN-2B
mucosal neuroma
Calcitonin is elevated in which type of thyroid Medullary thyroid cancer
cancer?
Low to normal serum Ca, low serum phosphate, Vitamin D deficiency (rickets)
high alkaline phosphatase, low 25-(OH) vitamin D,
high parathyroid hormone (PTH)
Normal serum Ca, low serum phosphate, very high Hypophosphatemic rickets or X-linked
alkaline phosphatase, normal vitamin D, failure to hypophosphatemic rickets
thrive, hypotonia, delayed dentition
What is the mode of inheritance of X-linked dominant
hypophosphatemic rickets?

High serum PTH, low serum Ca, high phosphate, Albright hereditary osteodystrophy
short stature, stocky habitus, soft-tissue (pseudohypoparathyroidism type 1A)
calcifications/ossifications, short fourth and fifth
metacarpal bones
Short stature with stocky body habitus, soft-tissue Pseudopseudohypoparathyroidism—due to
calcification/ossifications, short fourth and fifth paternal mutation
metacarpals with normal PTH, normal calcium,
and normal phosphate
Normal serum Ca, low serum phosphate, very high Oculocerebrorenal dystrophy (Lowe syndrome)
alkaline phosphatase, non-anion gap metabolic
acidosis, developmental delay, cataracts, glaucoma
A 7-year-old with obesity, hyperphagia, small Prader–Willi syndrome
hands and feet, small penis, cryptorchidism, and
cognitive deficiency
What is the chromosomal deletion of Prader–Willi Paternal chromosome 15q11-q13 deletion
syndrome?
Obesity, retinitis pigmentosa, hypogonadism, Bardet–Biedl syndrome or Laurence–Moon–
intellectual disability Biedl syndrome
Adolescent female, obesity, acanthosis nigricans, Polycystic ovary syndrome
HBA1c 6.9%, elevated testosterone and LH,
hirsutism, no ovarian cysts noticed on
ultrasonography
Failure to thrive, microcephaly, intellectual Smith–Lemli–Opitz syndrome (autosomal
disability, ptosis, strabismus, syndactyly, pyloric recessive)
stenosis, and low-plasma cholesterol
Polydipsia, hypernatremia, serum osmolarity Diabetes insipidus (DI)
> 300 mOSm/kg, urine osmolarity < 300 mOSm/
kg
Patient with meningitis on IV fluids, hyponatremia, Syndrome of inappropriate antidiuretic hormone
hypo-osmolality, elevated blood pressure, secretion (SIADH)
inappropriately concentrated urine, and high urine
sodium level
What is the best initial treatment for the patient Reduce IV fluid rate (fluid restriction)
with SIADH in the previous example?
A patient underwent neurosurgery for a brain Cerebral salt wasting
tumor, develops dehydration, hyponatremia, high
urine output, hypovolemia, low blood pressure,
high urine Na
Cerebral salt wasting is associated with which Atrial natriuretic peptide
hormone is being elevated?
What is the best treatment for a patient with Isotonic fluid hydration
cerebral salt wasting dehydration?
Patient with diabetes insipidus comes in for water Central diabetes insipidus
deprivation test, after administration of DDAVP
(desmopressin) the urine becomes concentrated
1076 O. I. Naga

Patient with diabetes insipidus comes in for water Nephrogenic diabetes insipidus
deprivation test, after administration of DDAVP
there is no effect on urine concentration
Child with obesity, height < 3rd percentile, blood Cushing syndrome
pressure > 95th percentile for age
A 7-year-old boy with a history of severe asthma, Adrenal insufficiency
presents with a 3-day history of worsening nausea,
abdominal pain, and vomiting, he was on a high
dose of inhaled steroids for 1 year. Lately, the child
is not compliant with medications. What is the
most likely cause of his symptoms?
Child is presents with fatigue, nausea, weight loss, Addison disease
hypotension, volume depletion, and diffuse
hyperpigmentation
Child with type 1 diabetes mellitus, well Addison disease
controlled, suddenly develops hypotension and
shock
Best initial treatment for a patient with diabetic IV hydration: 10 mL/kg of intravenous normal
ketoacidosis within the first hour who presents saline over 1 h
with volume depletion, e.g., tachycardia,
prolonged capillary refill time, and elevated blood
urea nitrogen and creatinine
The most common cause of death in children who Diabetic ketoacidosis (DKA)
have type 1 diabetes
What is the most common cause of recurrent Insulin omission
DKA?
The most common cause of death related to DKA Cerebral edema
in children
Adolescent female presents with recurrent vaginal Fasting blood glucose level
candidiasis, BMI > 97th percentile, hypertension,
acanthosis nigricans. What is the next best step?
Adolescent female presents with polyuria, Metformin
polydipsia, BMI > 97th percentile, hypertension,
acanthosis nigricans; her blood glucose level is
200 mg/dL, A1C is 7%. What is the best
treatment?
Adolescent female presents with polyuria, Insulin
polydipsia, BMI > 97th percentile, hypertension, Blood glucose level ≥ 250 mg/dL, A1C ≥ 8.5%
acanthosis nigricans; her blood glucose level is insulin is the best initial treatment
350 mg/dL, A1C is 10%. What is the best initial
treatment?
What is the A1C goal recommended by the A1C target < 7.5% should be considered but
American Diabetes Association for all pediatric individualized
age-groups with type 1 diabetes mellitus?
A 3-day-old infant, 10 lbs at birth, jittery Infant of a diabetic mother with hypocalcemia

A 9-year-old male with sweating, jitteriness, and Hypoglycemic episode
tachycardia with sudden onset of symptoms Treatment: 15 g of carbohydrate
A 9-year-old male who has altered mental status IM glucagon
glucose is noted to be 45 mg/dl. Best treatment?
An infant with a history of tetralogy of Fallot Hypoparathyroidism
presents with jitteriness and muscle twitching that
has been worsening over the past few days. Blood
glucose level is 85 mg/dL, and the calcium level is
7 mg/dL. What is the most likely cause?
A 5-day-old infant, small jaw, broad nose, DiGeorge/velocardiofacial (VCF)
tetralogy of Fallot, seizure
A 3-month-old male with elfin facies, Williams syndrome
supravalvular aortic stenosis, now with serum Ca
of 12.2
A 4-day-old male with hypoglycemia, Beckwith–Wiedemann syndrome
omphalocele, hemihypertrophy
Which childhood tumor is associated with Wilms tumor
Beckwith–Wiedemann syndrome?
A 10 lb plethoric neonate, requiring 15 mg/kg/min Congenital hyperinsulinism
dextrose infusion. The mother without gestational
diabetes mellitus (DM)
A 5-year-old male previously healthy with throat Ketotic hypoglycemia (treatment is IV dextrose)
pain and loss of appetite for 2 days, suddenly starts
feeling dizzy, jittery, becomes unconscious in ER;
the glucose level is 37 mg/dL, high level of serum
and urine ketone, undetectable serum insulin,
elevated serum cortisol, and growth hormone.
An 18-month-old thin boy with mild fever Ketotic hypoglycemia (diagnosis of exclusion)
overnight presents with loss of consciousness and
hypoglycemia
A 5-day-old male with a small phallus, jaundice, Hypopituitarism (adrenocorticotropic hormone
now with glucose of 45 mg/dl and ketones in urine (ACTH), growth hormone (GH) deficiency)
after 4 h of fasting
A 6-year-old with nighttime headaches, height has Intracranial tumor in the region of the pituitary
fallen from 25th percentile to 5th percentile over
1 year. Enuresis
An 18-month-old male, length, and weight Celiac/malabsorption
“stalled” for 9 months. Stools remarkably odorous
What are the components of metabolic syndrome? Impaired glucose
Low HDL
High triglycerides
Elevated blood pressure
Central obesity
1078 O. I. Naga
ORTHOPEDICS
Amr Abdelgawad
Last-Minute Review—Orthopedics Most Likely Answer

First newborn female, breech presentation, positive Developmental dysplasia of the hip (DDH)
Barlow
What is the imaging modality of choice in a Ultrasound (US) of the hips (< 6 months)
2-month-old girl with concern for DDH?
What is the imaging modality of choice in a Pelvis radiograph (> 6 months)
7-month-old girl with concern for DDH?
What is the earliest time for US screening for 6 weeks of age (before 6 weeks, overly sensitive
DDH? and can result in overtreatment)
A 1-month-old is diagnosed with DDH. What is Pavlik harness
the preferred treatment?
An 8-year-old boy presents with limping, pain in Legg–Calve–Perthes disease
the right hip and knee, plain radiograph shows
ossified and collapsed femoral epiphysis
Adolescent with obesity presents with limping, Slipped capital femoral epiphysis
pain in the right hip and knee, plain radiograph
shows displacement of the femoral epiphysis
A 5-year-old boy with upper respiratory Transient synovitis
symptoms, complaining of left leg pain and
difficulty walking, decreases movement of the left
hip. ESR and CRP are within normal ranges
A 5-year-old boy presents with left hip pain, fever Septic hip (pyogenic arthritis)
and limping; he appears ill, grimaces with any left
hip movement, limited range of motion, ESR and
CRP are significantly elevated, hip US shows left
hip effusion
What is the next best step in cases of pyogenic Antimicrobial to cover against Staphylococcus
arthritis? aureus and streptococcal species, and in young
children, Kingella kingae should also be covered
Urgent orthopedic consultation
A 12-year-old male presents with left knee redness, Distal femur osteomyelitis
pain, and swelling. There is a decreased range of
motion along with elevated WBC, CRP, and ESR
What is the most sensitive imaging modality to MRI
check for osteomyelitis?
Short umbilical cord, oligohydramnios, pulmonary Arthrogryposis
hypoplasia, joint contractures, micrognathia,
absent skin creases
Indications for radiographic evaluation of bow leg > 2 years of age, unilateral, progressive after
“genu varum” 1 year, thigh leg angle > 20°, suspected rickets
or associated deformities
A 3-year-old African-American girl with obesity Blount disease
has severe progressive genu varum; plain
radiograph shows proximal metaphyseal beaking

Basketball player presents with left knee pain, Osteochondritis dissecans
recurrent effusion, quadriceps atrophy, and pain
with range of motion; plain radiograph shows
subchondral fragment with a lucent line separating
it from the condyle
A 13-year-old female with right knee pain; she Recurrent patellar subluxation and dislocation
feels that her knee cap is unstable, parapatellar
tenderness, plain radiograph sunrise view shows
lateral tilt of patella
A 5-year-old has cystic mass in the back of the left Popliteal cyst (Baker cyst)
knee for 3 months, it is painless, with no
tenderness, normal range of motion
The best management of Baker cyst Observation for 12 months
Knee pain with prolonged sitting, activity, and Patellofemoral pain syndrome (PFPS)
climbing or descending stairs, feeling of knee
instability. Tenderness over the medial patellar
facet, pain with patellar compression, and mild
swelling
The best management of patellofemoral pain Ice, rest, NSAID, quadriceps and hamstring
syndrome strengthening
The most common cause of intoeing in children Femoral torsion
> 3 years
A 7-year-old girl, patellae are looking inward Femoral anteversion
(kissing patellae), running like an egg-beater,
always sitting in W position, internal rotation of
the hip is more than external rotation
Management of femoral anteversion Reassurance (spontaneous resolution in more
than 80% of the cases)
Are shoe wedges, twister cables, night splint, or Showed to be ineffective
discouraging W-sitting effective in cases of
femoral anteversion?
The most common cause of intoeing in children Tibial torsion
between 18 months and 3 years
A 2-year-old with both feet pointing medially, Internal tibial torsion
especially when running, patellae in both legs are
pointing anteriorly. The child trips frequently
Management of internal tibial torsion Reassurance (almost all cases resolve
spontaneously)
A 4-month-old with a curved foot; by drawing an Metatarsus adductus
imaginary line bisecting the foot, it passes laterally
to the fourth toe
The best management of metatarsus adductus Observation (if persists beyond 6 months and
deformity is rigid, a referral is necessary)
Newborn with a deformed foot; the foot can be Postural or positional (calcaneovalgus foot) this
everted and dorsiflexed (the foot touches the is not a clubfoot
anterior tibia)
1080 O. I. Naga

The best management of calcaneovalgus foot Observation—condition due to the intrauterine
position
Newborn male infant with turned inward right foot. Clubfoot or congenital talipes equinovarus
The right foot can be passively stretched almost to (TEV)
the midline. The ankle is in equinus (downward),
the foot is supinated (varus) and adducted,
dorsiflexion beyond 90° is not possible
Best management of clubfoot Serial casting (requires an immediate referral)
The most common neurological conditions Myelomeningocele and cerebral palsy
associated with clubfoot
The most common condition associated with cavus Charcot–Marie–Tooth syndrome
foot
A mother is concerned that her 6-month-old has a Reassurance (medial arch of the foot does not
flat foot develop until 4 years of age and reaches adult
value by 8 years)
A 3-year-old child with tiptoe walking, normal Physical therapy for 6 months for Achilles
neurological examination, the best course of action tendon stretching; if no improvement, orthopedic
referral
A 15-year-old presents with progressive back Scheuermann kyphosis
deformity, plain radiographs of the thoracic spine
shows 3 adjacent wedged vertebral bodies of at
least 5°
A 12-year-old female has spinal scoliosis detected Adolescent idiopathic scoliosis (AIS)
by school nurse; the scoliometer measures 7°
Cases with AIS should be referred to orthopedic if Scoliometer 7° or more, Cobb angle > 20°
Management of female adolescent with AIS and Bracing (if skeletal growth remaining)
Cobb angle > 25°
Management of female adolescent with AIS and Usually, surgery is required
Cobb angle > 50°
The indication for MRI in cases with scoliosis Pain, left thoracic curve, abnormal neurological
exam, infantile and juvenile types
Adolescent with low-back pain for a few months. Mechanical low-back pain
The pain is worse after physical activity or
prolonged sitting. O/E: pain is exaggerated with
lumbar flexion and bilateral rotation. Tenderness to
palpation along the lumbar paraspinal muscles;
tightness of the hamstring and calf muscles.
Normal neurologic examination. No other
symptoms. Normal spine radiograph
What is the best management in the previous case? Physical therapy (lumbar/core strength and
stability exercises)
A 10-year-old female does gymnastics; presents Spondylolysis
with low-back pain that increases with the
extension of the spine, plain radiograph shows
defect in pars interarticularis, oblique view shows
Scotty dog collar sign

A 10-year-old female does gymnastics; presents Spondylolisthesis
with low-back pain that increases with the
extension of the spine, plain radiograph shows
forward slippage in L5 over S1
Best initial management of spondylolysis NSAID and rest
Management of spondylolisthesis Referral to orthopedics
A 15-year-old boxer complaining of dull pain in Possible scaphoid fracture. (Radiograph is
radial aspect of the right wrist that is exacerbated usually negative in the first 2 weeks). Treat if
by clenching, and tenderness in the anatomic highly suspected
snuffbox; plain radiograph on the right wrist is
negative
The best management of scaphoid fracture Thumb spica splint and repeat radiograph in
2 weeks
The motor manifestation of posterior interosseous Finger drop (inability to extend the fingers at the
nerve injury metacarpophalangeal joint)
The motor manifestation of radial nerve injury Wrist drop and finger drop
The motor manifestation of ulnar nerve injury Partial claw hand
The motor manifestation of median nerve injury Inability to flex the index finger
The most common sports injury in the knee, e.g., Anterior cruciate ligament (ACL) injury
female playing soccer
A 14-year-old complains of right shoulder pain Anterior shoulder dislocation
after a fall, arm held in abduction, and externally
rotated, the shoulder is boxlike. Patient resists
adduction and internal rotation, plain radiograph
shows a subcoracoid position of the humeral head
in the AP view and humeral head lies anterior to
the “Y” in an axillary view
A 14-year-old complains of right shoulder pain Posterior shoulder dislocation
after an electric shock, the arm is held in adduction
and internal rotation, patient resists external
rotation and abduction. Plain AP radiograph shows
a humeral head that resembles an ice cream cone.
The scapular “Y” view reveals the humeral head
behind the glenoid (the center of the “Y”)
Child with anterior shoulder dislocation loses the Axillary nerve injury (check axillary nerve
pinprick sensation in the deltoid sensation before and after reduction)
Right shoulder pain after a fall during basketball Acromioclavicular joint disruption
practice, prominent clavicle with loss of the
normal contour of the shoulder, shoulder
radiographs show separation between the clavicle
and acromion
Right shoulder pain after a fall during basketball Acromioclavicular joint sprain
practice directly onto the lateral aspect of the right
shoulder, pain when adducting the arm across the
chest, there is mild swelling and tenderness at the
distal end of the clavicle, shoulder radiographs are
normal
1082 O. I. Naga

The most common ligaments affected in ankle Lateral ligaments of the ankle (anterior
sprain talofibular most common, calcaneofibular, and
posterior talofibular ligaments)
When can a patient with an ankle sprain go back to If no pain and painless range of motion
sports?
The best way to differentiate between an ankle Bony tenderness is usually a fracture
sprain and fracture
A 2-year-old boy fell 2 h ago; now he is refusing to Apply a cast on the left lower extremity and
walk. He appears to have tenderness over the distal repeat radiography in 2 weeks (possible toddler
third of the left tibia. Radiographs of lower fracture)
extremities are normal. What is the next best step?
A 12-year-old boy had a fracture of right tibia, Compartment syndrome. Presence of pain
fixed with an above-knee cast. He continues to despite fracture immobilization and pain
have pain afterward, the pain keeps getting worse medication is a red flag for compartment
despite the maximum dose of prescribed pain syndrome
medicine, any movement of the toes causes him
excruciating pain, also he has numbness between
the first 2 toes
What is the next best step in the previous case of Report immediately to the nearest ER
compartment syndrome? (immediate removal of cast and orthopedic
consultation)
The most common orthopedic complication of Compartment syndrome
snake bite in the extremities
A 12-year-old with right knee trauma. Knee Fibrous cortical defect (non-ossifying fibromas),
radiograph showed no fracture but incidentally Most cases are accidentally discovered in
found a small, well-defined radiolucent cortical radiographs taken for other reasons. No
lesion with a surrounding rim of sclerosis in the treatment is required in most cases
upper tibia. The longitudinal axis of the lesion is
parallel to the axis of the tibia
A 12-year-old with severe pain in the upper part of Osteoid osteoma
the right tibia at night improved dramatically with
ibuprofen; radiograph showed 1.5 cm sharp round
lesion (nidus) surrounded by a rim of radiodensity
A 2-year-old child suddenly stops moving his right Nursemaid elbow
arm after his brother forcibly pulled his hand
Short, webbed neck decreased the range of motion Klippel–Feil syndrome
in the cervical spine, low hairline. Fusion of
cervical vertebrae on radiograph
Common associations with Klippel–Feil syndrome Sprengel’s deformity (elevation of the scapula),
thoracolumbar anomalies, renal and cardiac
anomalies
SPORTS MEDICINE
Daniel Murphy
Last-Minute Review—Sports Medicine Most Likely Answer

Adolescent plays football, presents with pain in the Osgood–Schlatter disease
right knee, swollen tender tibial tubercle; plain
radiograph shows ossification of the tibial tubercle
with fragmentation
What is the best treatment of Osgood–Schlatter Icing, muscle stretching, and strengthening
disease? decrease activities triggering the pain, NSAIDs,
knee brace
An 8-year-old boy recently starts playing Sever disease
basketball for 2 h every day, he is complaining of
pain in both heels, the pain is worse when jumping
and with exercise. The exam is positive for
tenderness at both heels and and with dorsiflexion
of both feet
What is the best treatment of Sever disease? Icing, stretching of Achilles tendon, NSAIDs,
heel cups, avoid activities triggering the pain,
e.g., jumping
Adolescent girl is complaining of right hip pain Anterior inferior iliac spine (AIIS) apophyseal
that developed during track practice. She felt a pop avulsion injury (due to strong muscle contraction
in the front of her right hip and had immediate and skeletal immaturity and relatively weak
onset of pain. There is tenderness over anterior apophysis)
inferior iliac spine, pain and weakness with
resisted hip flexion, and pain with passive
extension of the hip. What is the most likely
diagnosis?
Healthcare providers should educate athletes at Strengthening, balance, and plyometric (jump)
high risk for ACL tear about neuromuscular training, proper knee position and technique
training programs that reduce the risk of injury.
What are the components of neuromuscular
training?
What are the highest rates of dental injuries among Basketball, baseball, wrestling, and soccer
high school sports in boys?
What are the highest rates of dental injuries among Field hockey, softball, basketball, and lacrosse
high school sports in girls?
What is the best protective gear during sports that Mouthguard
decreases oral injuries, including tooth avulsions,
tooth fractures, and lacerations?
Adolescent with a history of 3 concussions is Neuropsychological testing
suffering from forgetfulness and difficulty
concentrating since last concussion, which was
2 months ago. What is the best diagnostic test to
identify impaired cognitive function?
1084 O. I. Naga
Last-Minute Review—Sports Medicine Most Likely Answer

Adolescent with a history of scoliosis is in your Echocardiography (Marfan syndrome is a high
office for sports clearance. Physical examination is risk of aortic root rupture and aortic dissection)
significant for pectus excavatum, hypermobility of
the wrist and finger joints, long and thin fingers,
arm span–to–height ratio that is greater than 1.05
What is the best treatment of apophyseal avulsion Rest and protected weight-bearing; surgery is
injuries? rarely indicated
Adolescent boy presents to your office for Syncope during exercise
preparticipation evaluation before football season.
He has a history of 2 episodes of syncope. What is
the most important finding that warrants a through
cardiology evaluation?
What is the best drink for sports activities lasting Water is enough for hydration
1 h or less?
What is the best drink for sports activities lasting Sports drinks (contain electrolyte and sugar;
longer than 1 h? may encourage for hydration with longer
activities)
A father is asking about energy drinks for his Not recommended for young children and
children during sports adolescents (due to high caffeine level in energy
drinks)
An athlete has been doing strenuous exercise for a Heat exhaustion
prolonged period in hot weather, excessively
sweating, dizziness, thirst, weakness, headache,
malaise, tachycardia, and the temperature is 103 °F
An athlete has been doing strenuous exercise for a Heat stroke
prolonged period in hot weather, presents with dry
and hot skin, feeling dizzy, weak, altered mental
status, low blood pressure, and tachycardia, and
the temperature is 105 °F
What is the next best step in an athlete with Rapid and immediate cooling (ice water bath) at
suspected heat stroke? the scene then transfer to the ED
An athlete is complaining of headaches, dizziness, Remove from sports. Neurocognitive rest
poor concentration after a head concussion while
playing volleyball. What is the next best step?
Adolescent boy is presenting with a large swelling Soft-tissue hematoma
in the left thigh after hitting another player during
the game, radiograph on the left femur is normal.
What is the most likely diagnosis?
A 17-year-old boy is interested in building Anabolic steroids intake
muscles, the mother is concerned about his acne,
aggressive behavior. Gonads are small for age.
What is the most likely underlying cause?
RHEUMATOLOGY
Dawn M. Wahezi
Last-Minute Review—Rheumatology Most Likely Answer

A 7-year-old with morning stiffness, knee and Oligoarticular juvenile idiopathic arthritis (JIA)
ankle swelling for 2 months, ESR is normal,
antinuclear antibody (ANA) 1:160
A 2-year-old female with recently diagnosed oligo Chronic anterior uveitis
JIA and positive ANA requires frequent screening
for this comorbidity
Fatigue, weight loss, arthritis in multiple joints for Polyarticular JIA
> 6 weeks, positive RF, anti-cyclic citrullinated
peptide antibodies present and ANA is negative
Fatigue, weight loss, no fever, arthritis in multiple Polyarticular JIA with an increased risk of
joints, negative RF, ANA is positive uveitis
A 5-year-old girl recently diagnosed with JIA, her Every 3–4 months (JIA, < 7 years and positive
ANA is positive; how frequently does she need ANA is the highest risk of uveitis)
screening for uveitis?
A 9-year-old girl recently diagnosed with JIA, her Every 6 months (JIA, > 7 years and positive
ANA is positive, how frequently does she need ANA)
screening for uveitis?
An 8-year-old with knee pain for 6 weeks, noted to Inflammatory arthritis
have pain, swelling, decreased range of motion,
difficulty bearing weight, synovial fluid shows
decreased viscosity and WBC 15,000
Fever, salmon-colored rash with fever and hot Systemic JIA
showers, arthritis in major joints,
hepatosplenomegaly, leukocytosis, thrombocytosis,
anemia of chronic disease, elevated ESR, negative
RF, and negative ANA
Side effects include immunosuppression, adrenal Corticosteroids
suppression, weight gain, cushingoid facies,
diabetes and acne
Child with systemic JIA presents with elevated Macrophage activation syndrome
liver enzymes, prolonged PTT, positive D-dimer,
thrombocytopenia, hyperferritinemia, and low ESR
Malar rash, arthritis, proteinuria, leucopenia, Systemic lupus erythematosus (SLE)
thrombocytopenia, positive ANA, and anti-dsDNA
An African-American girl with pericarditis, SLE
pleurisy, recurrent oral ulcers, hemolytic anemia,
and RBC casts in urine
This test is very sensitive but not specific for SLE Antinuclear antibody (ANA)
Autoantibodies associated with arterial/venous Antiphospholipid antibodies
thrombosis or recurrent miscarriage (in patients
with or without SLE)
1086 O. I. Naga

The most severe type of lupus nephritis resulting in Diffuse lupus nephritis (membranoproliferative,
hematuria, proteinuria, elevated blood pressure and class IV)
can lead to end-stage renal disease
Neonate born with heart block, annular Neonatal lupus
erythematous plaques, anemia, thrombocytopenia,
and elevated liver enzymes, positive SSA (Ro) and
SSB (La) antibodies
Recurrent parotitis, xerophthalmia, conjunctivitis, Sjögren syndrome
xerostomia, positive ANA, RF, and anti-Ro
A 7-year-old female, with proximal muscle Juvenile dermatomyositis
weakness in both sides, arthralgia, heliotrope rash,
elevated creatine phosphokinase (CPK) and LDH
A 6-year-old female with difficulty climbing stairs Juvenile dermatomyositis
and voice change, Gottron papules and abnormal
nailfolds, and telangiectasias
A 15-year-old had diarrhea positive for Yersinia Reactive arthritis
2 weeks ago, now is having conjunctivitis,
urethritis, arthritis of the hip and knee
Adolescent with inflammatory bowel disease Arthritis-related to IBD
(IBD) has arthritis
An 8-year-old, pain in the sacroiliac joint, Enthesitis-related arthropathies
tenderness, stiffness and joint pain in the morning
that improves with activity, and positive HLA-B27
Child with nail pitting, psoriasis, arthritis, positive Juvenile psoriatic arthritis
ANA
Adolescent with recurrent oral and genital ulcers, Behçet disease
positive pathergy test
Adolescent girl with chronic left foot pain, Complex regional pain syndrome or reflex
minimal touch aggravates the pain, foot is swollen, sympathetic dystrophy (RSD)
warm to touch, and mottled skin
A 7-year-old boy with pain in both legs, worse in Growing pain
the evening, sometimes awakens him from sleep,
no fever, no limping, joints are normal on exam,
pain responds to ibuprofen and heat massage
Adolescent, 1 year with fatigue, multiple areas of Fibromyalgia
pain, tenderness, no signs of inflammation, and
labs are normal
A 5-year-old boy with acute onset palpable Henoch-Schönlein purpura (HSP)
purpura on lower extremities, joint swelling and
abdominal pain, labs reveal normal CBC, PT and
PTT, positive proteinuria
An 18-month-old with fever for 6 days, rash, Kawasaki disease
conjunctivitis, strawberry tongue, and erythema of
the palms and soles
The primary treatment for Kawasaki disease, IVIG, aspirin
ideally given between day 5 and 10 of illness

A 15-year-old female with fatigue, weight loss, Granulomatous polyangiitis (GPA, formerly
recurrent sinusitis, and joint pain. Labs reveal Wegener granulomatosis)
hematuria, proteinuria, and positive cANCA
Pain, numbness, and discoloration of fingers (white Raynaud’s disease
then blue then red) that is triggered by cold
weather
A 12-year-old female with a linear hyperpigmented Localized scleroderma
lesion on her leg that appears white and sclerotic in
the center and has an erythematous border
A 14-year-old female with severe Raynaud disease Systemic sclerosis
with ulceration on her fingertip, tightening of her
skin, sclerodactyly, positive ANA, positive
anti-Scl-70
A chest radiograph with pulmonary infiltrates and Sarcoidosis
hilar adenopathy, biopsy with non-caseating
granulomas, elevated ACE
Recurrent knee arthritis in an otherwise well child Lyme arthritis
with a prior history of camping in the woods
Newborn infant presents a few hours after birth Neonatal myasthenia gravis
with hypotonia, facial muscle weakness, ptosis,
weak cry, respiratory distress, the mother has a
history of muscle weakness
Adolescent with muscle weakness, worsens with Juvenile myasthenia gravis
repetitive movement and at the end of the day,
difficulty breathing, abnormal ocular movement
A 3-year-old child from the Middle East, recurrent Familial Mediterranean fever
fever and abdominal pain, during the episode the
ESR and CRP are elevated, WBC 25,000
Child with fever for 3–5 days every month PFAPA (periodic fever, aphthous stomatitis,
associated with mouth ulcers, throat pain, cervical pharyngitis, and cervical adenitis)
lymphadenitis. The patient is well in- between
episodes
NEUROLOGY
Ivet HartonianJong W. Yoo, and Jason T. Lerner
Last-Minute Review—Neurology Most Likely Answer

An 18-month-old turns cyanotic associated with a Reassurance (cyanotic breath-holding spell)
brief loss of consciousness that occurred during a
temper tantrum
An 18-month-old turns pale with limp jerking and Reassurance (pallid breath-holding spell)
brief loss of consciousness that occurred after the
child was scared by his sibling
1088 O. I. Naga

A 4-month-old infant is having episodes of tonic Sandifer syndrome
neck extension and dystonic posturing of trunk
associated only with feedings. Has a normal
neurologic exam
A premature infant has brief jerking of the right Neonatal seizure
upper extremity that cannot be suppressed
A previously healthy 16-month-old boy has 60 s Simple febrile seizure
generalized seizure in the setting of febrile illness
(not involving the CNS) and is now acting normal
A previously healthy 16-month-old boy has had 2 Complex febrile seizures
febrile seizures in the last 24 h, and the infant is
now acting normal
What is the recurrence risk after the first simple Approximately 30%
febrile seizure?
What is the risk of developing epilepsy in children Approximately 2%
with simple febrile seizures?
An 8-year-old boy is having multiple brief daily Absence seizure (petit mal seizure)
episodes of behavioral arrest and eye fluttering
with an EEG showing 3 Hz/s spike-and-wave
discharges
The first-line treatment for absence seizures Ethosuximide
Antiseizure medication that should be avoided in Valproic acid
women of child-bearing age due to teratogenicity
A 6-month-old infant having episodes of tonic Infantile spasms
flexion of trunk, head, and extremities, occurring
in clusters
Triad of infantile spasms, hypsarrhythmia on EEG, West syndrome
developmental regression
A 3-year-old boy with a prior history of infantile Lennox–Gastaut syndrome
spasms who now has intellectual disability,
multiple seizure types, EEG showing slow spike-
wave activity
An 16-year-old girl who is an excellent student has Juvenile myoclonic epilepsy
a generalized tonic-clonic seizure after a sleepover
party with her friends. She also reports having
jerking movements of her arms in the mornings
A 5-year-old with nighttime seizures involving the Rolandic epilepsy with centrotemporal spikes
face and focal centrotemporal spikes in sleep
A 3-year-old with language regression and Landau–Kleffner syndrome
continuous spike-wave discharges in slow wave
sleep
A 9-year-old previously healthy girl with Rasmussen encephalitis
intractable focal seizures as well as hemiparesis
and cognitive decline. MRI of the brain shows
atrophy of one hemisphere

An infant with rapid head growth, full fontanel, Hydrocephalus
irritability, vomiting
The most common cause of macrocephaly Benign familial macrocephaly
An infant with failure to thrive, developmental Lissencephaly
delay, intractable seizures with an MRI showing a
“smooth brain”
Elevated maternal alpha-fetoprotein, an infant born Anencephaly
with a large cranial defect, abnormalities of the
face and eyes, without a cortex but an intact
brainstem
Global intellectual disability, brain MRI showing Schizencephaly
bilateral clefts within the cerebral hemisphere
An infant with a sacral tuft of hair and normal Spina bifida occulta
neurologic exam
MRI showing downward displacement of the Arnold–Chiari malformation
cerebellar tonsils through the foramen magnum
Cystic expansion of the fourth ventricle in the Dandy–Walker syndrome
posterior fossa, associated with hydrocephalus,
cerebellar ataxia, and associated with corpus
callosum agenesis
Newborn with a skull defect, a sac-like protrusion Encephalocele
containing brain material
Infant born with a short neck, very low hairline in Klippel–Feil syndrome
the back of the head, and limited range of motion
in the neck
Child with a stroke-like event has MRI with the Moyamoya disease
appearance of a “puff of smoke”
Adolescent girl presents with ptosis and double Juvenile myasthenia gravis
vision and is also complaining that she feels
weaker by the end of the day
Preschool age boy has a history of toe walking, Duchenne muscular dystrophy
frequent falls, and enlarged calves. O/E: he has
significant proximal muscle weakness, positive
Gower sign, and laboratory evaluation shows
elevated CPK (creatine phosphokinase)
A 10-year-old boy presents frequent falls, and Becker muscular dystrophy—older onset and
weakness for 3 months. O/E: he has mild proximal milder form
muscle weakness, and calf pseudohypertrophy and
his echocardiogram shows cardiomyopathy,
laboratory shows elevated serum CPK
Newborn infant presents with hypotonia, Congenital myotonic dystrophy
respiratory distress, and facial muscle weakness.
The genetic test is positive for CTG trinucleotide
repeat
1090 O. I. Naga

Group of disorders characterized by decreased Charcot–Marie–Tooth syndrome
deep tendon reflexes, decreased proprioception,
and a vibratory sense that is caused by defective
peripheral nerve demyelination
A 12-year-old girl previously healthy over few Friedreich ataxia—GAA trinucleotide repeat
months presents with progressive clumsiness, gait (autosomal recessive and presents in older
and limb ataxia, recurrent falls, rapid, jerky children)
movements of both eyes, areflexia, lower extremity
weakness, dysarthria, and dysphagia. Positive
frataxin gene sequencing, associated with
cardiomyopathy and increased risk of diabetes
mellitus
A 3-year-old girl presents with recurrent Ataxia–telangiectasia (autosomal recessive and
respiratory infections, clumsiness, gait and limb presents in young children)—mutation of the
ataxia, recurrent falls, oculomotor apraxia, ATM gene
choreoathetosis, dysarthria, and ocular
telangiectasias, and serum α-fetoprotein is elevated
Adolescent with a history of herpes zoster presents Ramsay Hunt syndrome
with peripheral nerve paralysis, facial pain, and
deafness
History of diarrhea followed by progressing Guillain–Barré syndrome
ascending weakness and loss of deep tendon
reflexes with CSF showing elevated protein
A 4-month-old infant with severe hypotonia and Spinal muscular atrophy
feeding difficulty. O/E: the infant is in frog-leg
position and has tongue fasciculations
Progressive weakness in legs with focal back pain, Transverse myelitis
bowel and bladder dysfunction and sensory level
on the exam. Eventually develops into spastic
diplegia
A 6-month-old consistently reaches for toys with Central or peripheral neurologic abnormality of
the right hand. What is the most likely underlying the opposite side, including hemiparesis
cause?
An 18-month-old boy with a history of Spastic diplegic cerebral palsy
prematurity, including bilateral intraventricular
hemorrhages, who is brought in for evaluation
because he is not walking and has increased tone
in his legs. Scissoring of the legs is noted when he
is held in a vertical position
Child with dyskinetic cerebral palsy and a history Kernicterus
of elevated bilirubin
A school-age child develops abnormal limb Sydenham chorea
movements a few weeks after a group A beta-
hemolytic strep infection

An 18-month-old girl with acquired microcephaly, Rett syndrome
language regression, repetitive hand-wringing
movements, loss of purposeful hand use. Genetic
testing reveals a mutation in the MECP2 gene
Adolescent girl is complaining of right frontal Migraine headache
pulsating headache with photophobia and nausea.
She reports that during the headache episodes, she
prefers to be in a dark, quiet room. Her father and
paternal grandmother also get headaches
Adolescent complaining of a mild headache Tension headache
described as “band-like” around the head.
Headache is responsive to over-the-counter
analgesics
Adolescent girl with a BMI more than 98th % Idiopathic intracranial hypertension
presenting with headaches, nausea, vomiting, (pseudotumor cerebri)
double vision, papilledema, and inability to abduct
her left eye. What is the most likely underlying
cause?
A 1-year-old girl presents with an increasing Referral to a pediatric ophthalmologist to check
number of café-au-lait spots all over her body. She for Lisch nodules annually
has more than 6 macules, each macule measuring
more than 5 mm. The rest of the exam is normal.
No family history of neurofibromatosis. What is
the next best step?
The child in the previous example is positive for Genetic consultation, annual pediatric
Lisch nodules. What are the recommendations? ophthalmology evaluation, regular
developmental assessment, and regular blood
pressure monitoring
Multiple café-au-lait spots, Lisch nodules on Neurofibromatosis type 1
ophthalmology exam, and presence of multiple Autosomal dominant
neurofibromas
Presents with ringing in the ears; imaging shows Neurofibromatosis type 2
bilateral vestibular schwannomas Autosomal dominant
A 10-month-old infant presents with infantile Tuberous sclerosis complex
spasms and is noted to have multiple
hypomelanotic macules (ash leaf spots). MRI brain
shows cortical tubers
History of port-wine stain, seizures, and glaucoma Sturge–Weber syndrome
Child presenting with chronic back pain, lower Tethered cord syndrome
extremity weakness, leg length discrepancy, foot
deformities, scoliosis, neurogenic bladder, and
recurrent urinary tract infections. There is no acral
hair or skin abnormalities in the lower back
Toddler refusing to walk or stand, with back Diskitis
tenderness and elevated ESR
1092 O. I. Naga

The child with a ventriculoperitoneal (V/P) shunt Shunt infection—possible brain abscess
with a triad of high fever, focal neurologic deficits,
and headache
Child with recurrent throat clearing, facial Tic disorder (Tourette syndrome if symptoms
grimacing, and grunting, but otherwise acting > 12 months)
normal
What is the first-line therapy for tic disorder with Behavioral modification
no other complications?
An infant with nystagmus, titubation, and Spasmus nutans
torticollis
A teenager with excessive daytime sleepiness, Narcolepsy
sudden episodes of loss of muscle tone and
hallucinations when going to sleep
A 9-year-old has a sudden onset of severe Vasovagal syncope
abdominal pain, becomes pale, feels dizzy, and her
vision slowly goes black followed by loss of
consciousness for a few seconds and quick return
to baseline
The reflex that appears around 8–9 months in Parachute reflex
preparation for a child to stand and walk
OPHTHALMOLOGY
Violeta Radenovich
Last-Minute Review—Ophthalmology Most Likely Answer

A 5-day-old infant with severe bilateral purulent Neisseria gonorrhoeae conjunctivitis
conjunctivitis and severe conjunctival chemosis.
What is the most likely organism?
A 5-day-old newborn presents with severe bilateral IM or IV 3rd generation cephalosporin, topical
purulent conjunctivitis, severe conjunctival erythromycin, ophthalmology consultation
chemosis. What is the best treatment?
A 10-day-old infant with mild to moderate Chlamydia conjunctivitis
purulent discharge also associated with a cough
and congestion. What is the most likely organism?
A 14-day-old infant presents with mucoid Oral erythromycin. Erythromycin ophthalmic
discharge from both eyes and eyelid swelling. ointment 4 times a day for 1 week
What is the best treatment?
Excessive tearing, photophobia, frequent spasms of Congenital glaucoma (immediate referral to
the eyelid, corneal clouding and enlargement of the pediatric ophthalmology)
eye
A newborn is being evaluated in the office for Immediate referral to ophthalmology—concern
leukocoria. The reflexes are absent in both eyes. for cataract or retinoblastoma

An 8-week-old male infant with right eye more Nasolacrimal duct obstruction (topical antibiotic
watery than the left. There is a golden-colored if suspected bacterial infection)
crust on his eyelashes, more prevalent in the
morning. No redness
What is the best initial treatment of nasolacrimal Lacrimal sac massage 2–3 times daily
duct obstruction?
Most of the cases of nasolacrimal duct obstruction 6 months to 1 year with no need for probing or
spontaneously resolve at what age? surgery
A 2-month-old baby boy presents with alternating Strabismus—if both eyes are alternating,
deviations in both eyes, no other symptoms monitor till 3 months of age (refer if persists)
A 2-month-old infant presents with left eye Strabismus—if only one eye is deviating, refer
deviated inward with no other symptoms to ophthalmology to exclude underlying
pathology
The infant in the previous example continued to Referral to a pediatric ophthalmologist
have left eye deviation at 4 months well visit
How long can a newborn be monitored for poor If persist beyond 3 months of age must be
tracking, lack of fixation, head tilt, nystagmus, or referred to a pediatric ophthalmologist
squinting?
A 9-month-old boy with crossed eyes. O/E: Reassurance (pseudostrabismus)
corneal light reflex is centered in both pupils
equally; cover test shows no ocular deviation
A 9-month-old boy with crossed eyes. O/E: Referral to a pediatric ophthalmologist
corneal light reflex is asymmetric; the cover test
shows ocular deviation
Red reflex is asymmetric, absent, dull, or opaque; Referral to ophthalmologist
dark spots in the red reflex; or leukocoria (white
reflex). What is the next step?
What is the major consequence of delaying the Amblyopia (lazy eye)
treatment of strabismus or cataract in pediatric
patients?
A 6-month-old infant presents with nystagmus, Spasmus nutans (often disappears after a few
head nodding, and torticollis. The nystagmus is years)—brain MRI on spasmus nutans patients
disconjugate, high frequency, small amplitude, to rule out optic nerve glioma that can present
pendular, and intermittent exactly like spasmus nutans
Child presents with swelling in the eyelid, Periorbital cellulitis (may be treated with an oral
hyperemia, normal vision, no pain with eye antibiotic as an outpatient)
movement, no decrease in eye movement. What is
the most likely diagnosis?
Child with a fever, malaise, proptosis, decreased Orbital cellulitis (admit for IV antibiotics and
vision, pain with eye movement, orbital pain and ophthalmology consultation)
tenderness, decreased eye movement, dark red
discoloration of the eyelids, chemosis, hyperemia
of the conjunctiva. What is the most likely
diagnosis?
Child is presenting with a painful, warm, swollen, Warm compresses and massages, topical
red lump on the eyelid. What is the best treatment? antibiotic if the lesion is draining
1094 O. I. Naga

Child is presenting with a painless nodule on the Referral to a pediatric ophthalmologist
left upper eyelid for 5 months not responding to
conservative measures (warm compresses and lid
hygiene). What is the next best step?
A 5-year-old boy presents with eye pain, foreign Examine the eye with fluorescein stain (corneal
body sensation, and tearing after self-inflicted eye abrasion)
injury with a sharp pencil. What is the next best
step?
Management of corneal abrasion Topical antibiotic, an oral analgesic, refer to an
ophthalmologist if no improvement in 24 h
Child is presenting with sudden onset of right eye Ophthalmology consult to rule out corneal
discomfort and blurring of vision after exposure to laceration and intraocular foreign bodies
flying debris of broken glass. What is the next best
step?
A 7-year-old is noted to have blood in the anterior Hyphema—emergent ophthalmology consult
chamber of the eye after blunt trauma and pain Sickle cell screening if African-American
with extra-ocular movements
Management of hyphema Ophthalmology consult, 45° bed elevation, bed
rest, eye shield, analgesia, sedation, topical
cycloplegic, and topical steroids
Child is complaining of significant pain, bruising, Orbital floor fractures (due to inferior rectus
and swelling in the periorbital area after eye muscle entrapment)
trauma; “sunken” appearance to the eye on the
affected side; decreased sensation to the cheek,
upper lip, and upper gingiva on the affected side;
and limitation of upward gaze on the affected side
Adolescent girl with obesity is complaining of Papilledema (untreated pseudotumor cerebri can
pounding headache, double vision, nausea, and result in permanent vision loss)
vomiting; the headache is worse when she is
leaning forward. Her vital signs are normal, but
she is unable to abduct her right eye. What is the
most likely finding in her eye exam?
Child with pink eye, fever, cloudy rhinorrhea, Reassurance (pharyngoconjunctival fever
cough, headache, pharyngeal redness with scant commonly caused by adenovirus)
exudates, a palpable right preauricular lymph node, Treatment: cold compresses to the eyes,
profuse tearing, and edematous nasal mucosa. The analgesics, rest, and fluids
right eye conjunctiva is hyperemic, and tiny
follicles are present on the inner lower lid. What is
the best treatment?
A 7-year-old girl is noted to have a large bloody Reassurance (viral subconjunctival hemorrhage
blotch under the conjunctiva, no history of trauma; [enterovirus, or adenovirus infection])
she has a runny nose and congestion
A 7-year-old is noted to have a small area of Reassurance (subconjunctival hemorrhage)
unilateral eye redness in the sclera. The redness
was noticed after a forceful sneeze

Child with watery, itchy eyes bilaterally, mild Allergic conjunctivitis
eyelid edema, along with conjunctival erythema.
No mucoid or purulent discharge
Child is being treated for allergic conjunctivitis for Referral to an ophthalmologist (topical
2 weeks with oral and topical antihistamine eye ophthalmic steroids require monitoring of eye
drops with no improvement. What is the next best pressure)
step?
A 3-year-old boy presents with different stage skin Child abuse
bruises; fundus examination shows bilateral
multilayered flame shaped retinal hemorrhages.
Night blindness, flashes of light, visual loss. O/E: Retinitis pigmentosa
optic nerve waxy pallor, mid-peripheral retinal
hyperpigmentation, retinal arteriolar attenuation
Pigmentary retinopathy, polydactyly, truncal Bardet–Biedl syndrome
obesity, kidney dysfunction, short stature
Syndromes associated with retinitis pigmentosa Alport syndrome, Waardenburg syndrome,
and hearing loss Refsum disease, Usher syndrome
A 9-year-old girl with a history of short stature, Brain MRI (optic nerve atrophy can be
vision 20/40, her eye exam is significant for optic associated with a brain tumor)
nerve atrophy. What is the next best step?
Risk factors commonly associated with retinopathy Birth before 30 weeks gestation, or low birth
of prematurity (ROP) weight < 1500 g
Who should screen preterm infants at risk for Pediatric ophthalmologist with experience in
ROP? ROP
Do preterm infants at risk of ROP should be Yes. Within 4–6 months after discharge because
followed by an ROP experienced ophthalmologist of risk of developing strabismus, amblyopia,
after discharge from the NICU high refractive errors, cataracts, and glaucoma
EAR, NOSE, AND THROAT
Last-Minute Review—Ear, Nose, and Throat Most Likely Answer

Newborn with isolated preauricular skin tags Renal US is not indicated if no other congenital
anomalies or risk factors
What is the risk of permanent hearing impairment 5-fold higher compared to the general
in a newborn with isolated preauricular skin tags or population
pits?
Prior to discharge, newborn hearing screen refers Refer for acute brainstem response (ABR)
to the right (i.e., did not pass the hearing test in the testing
right ear). Repeat testing also refers to the right.
Which antibiotic often used to treat newborn sepsis Gentamicin
that may cause ototoxicity?
1096 O. I. Naga

Child with acute otitis media or externa and Aminoglycosides
perforation of tympanic membrane—which topical
antibiotic drops should be avoided to prevent
ototoxicity?
A 12-month-old child with severe bilateral Cochlear implant
sensorineural hearing loss. What is the best
treatment?
What is the best audiometric test for an infant Visual reinforcement/behavioral audiometry
6–9 months or for older children with
developmental delay?
What is the best audiometric test for a child as Play audiometry
young as 2.5 years
What is the best audiometric test for children Conventional audiometry: pure-tone, speech
> 4 year, and adolescents?
What is the hallmark sign of otitis externa? Tenderness of the tragus or pinna
Child with persistent purulent otorrhea for more Referral to otolaryngologist
than 2 weeks despite treatment with oral and
topical antibiotics
Child with persistent otorrhea for more than Cholesteatoma (collection of squamous
6 weeks and not responding to oral and topical epithelial cells and keratin within the middle
antibiotics. What is the most frequent cause? ear)
Child presents with persistent ear discharge more Methicillin-resistant Staphylococcus aureus
than 3 months despite the treatment with multiple (MRSA) is most common isolate, Pseudomonas
courses of topical and systemic antibiotics. What is is also a common cause
the most common bacteria associated with chronic
suppurative otitis media (CSOM)?
Adolescent is complaining of nasal obstruction, Prompt drainage of nasal septal hematoma to
pain, and rhinorrhea after nasal trauma. O/E: prevent nasal cartilage ischemia, necrosis, and
intranasal cavity reveals a tense red mass on each deformity
side of the nasal septum. What is the next best
step?
Adolescent wrestler with blue swelling and redness Auricular (ear pinna) hematoma—urgent
in the right ear pinna, occurred during a school aspiration of the hematoma and pressure
match dressing
A 7-year-old child had tympanostomy tubes placed Referral to ENT for surgical removal
4 years ago because of acute otitis media with (tympanostomy tubes that remain in place for
effusion and conductive hearing loss. O/E: you longer than 3 years should be surgically
clearly visualize a white tympanostomy tube in the removed)
right tympanic membrane. What is the next best
step?
How long is a tympanostomy tube expected to 12–18 months
remain in place?
Child has otitis media with effusion (OME) less Tympanostomy tube insertion is not indicated
than 3 months
Child has OME lasting 3 months with conductive Tympanostomy tube insertion is indicated
hearing loss

Child has recurrent acute otitis media with OME at Tympanostomy tube insertion is indicated
the time of presentation
Child with bilateral or unilateral OME lasting at Tympanostomy tube insertion is indicated
least 3 months together with risk factors for
speech, language, or learning problems (e.g.,
neurodevelopmental disabilities, craniofacial
anomalies)
A 5-year-old with nasal discharge, congestion, and Acute bacterial sinusitis (duration of symptoms)
cough for 10 days without improvement
A 5-year-old with temperature 101.3 °F with Acute bacterial sinusitis (severity of symptoms)
purulent rhinorrhea for 3 days
A 5-year-old with worsening of nasal congestion Acute bacterial sinusitis (worsening of
or rhinorrhea, cough, and fever after a 3- to 4-day symptoms)
period of improved symptoms
Child presents with a 1-week history of fever of Acute sinusitis
102 °F, cough, bilateral purulent nasal discharge, First-line treatment: amoxicillin clavulanate for
and frontal sinus tenderness 10–14 days
Child presents with nasal congestion, post nasal Chronic sinusitis
drip, altered sense of smell, as well as facial
pressure for over 3 months
Child with an isolated fracture in the paranasal 1-week course of oral antibiotics and oral
sinus. What is the best treatment? analgesics, referral in 1 week to ENT or a
surgeon specialized in facial trauma
What are the sinus precautions in cases of To avoid swimming, blowing the nose, playing
paranasal sinus fractures? wind instruments, and use of drinking straws
A 6-year-old boy presents with throat pain, fever, 10-day course of oral penicillin V
headache, and abdominal pain. Rapid antigen
detection test for group A Streptococcus is
positive. What is the best treatment?
A 6-year-old boy presents with the third episode of Clindamycin for 10 days
streptococcal pharyngitis in the last 3 months.
Rapid antigen detection test for group A
Streptococcus is positive. He was treated
previously with penicillin V and amoxicillin. What
is the next best treatment?
A 6-year-old boy presents with throat pain, fever, Clindamycin for 10 days
positive. He had an anaphylactic reaction to
penicillin. What is the best treatment?
A 6-year-old boy presents with throat pain, fever, Oral cephalosporin for 10 days
positive. He had a non-anaphylactic reaction to
penicillin. What is the best treatment?
1098 O. I. Naga

A 5-year-old boy presents with the insidious onset Retropharyngeal abscess
of fever, sore throat, neck stiffness, tachypnea,
drooling, and stridor. Lateral neck radiograph
shows thickened prevertebral soft tissues
What is the next best step in the previous case with Airway management, IV fluids, IV antibiotics,
retropharyngeal abscess? emergent ENT consultation
Adolescent female presents with fever, sore throat, Peritonsillar abscesses
difficulty opening her mouth, muffled voice, and
dysphagia. She has tender anterior cervical
lymphadenopathy. Her right tonsil is erythematous
and enlarged, pushing her uvula to the left
What is the next best step in the previous case with Needle aspiration of her right tonsil (diagnostic
peritonsillar abscess? and therapeutic)
A 9-month-old presents with fever, ear tugging, Amoxicillin 90 mg/kg/day for 10 days
and runny nose. Both tympanic membranes are
bulging; this is the first ear infection. What is the
first-line treatment?
The same child presents to the office 3 weeks later Amoxicillin/clavulanate—due to treatment
with the same symptoms. Which antibiotic should failure within the last 30 days
be used?
A 2-year-old child presents with fever and purulent Amoxicillin/clavulanate—likely due to non-
conjunctivitis. Physical exam shows bulging of the typeable Haemophilus influenzae with
tympanic membrane. Which antibiotic should be concurrent bacterial conjunctivitis
used?
Child presents with fever, tenderness, and edema in Mastoiditis—needs ENT consult and IV
the postauricular region. Child was diagnosed with antibiotics
otitis media recently, but the parent was not
compliant with therapy
Newborn child with severe cyanosis that improves Bilateral choanal atresia—requires immediate
with crying. Nurse attempts to pass a 6 French airway, can also be unilateral (less severe) and
catheter and is not successful associated with CHARGE
Child with chronic nasal congestion, mucoid Sweat chloride test
rhinorrhea, and noisy breathing for several months.
No history of recurrent serious bacterial infections
and normal weight for age. On examining the nasal
passages, you note glistening, bluish-gray, grape-
like masses bilaterally. What is the next best test?
Children with nasal polyps should be screened for Cystic fibrosis
The most common cause of epistaxis in a child Trauma secondary to digital manipulation
A 2-year-old with unilateral rhinorrhea and foul Foreign body in the nose
smell from the left nostril. The child is otherwise
acting normal?
Child presents with runny nose, congestion, itchy Allergic rhinitis (under eye circles are called
eyes, sneezing, and darkened skin around the eyes allergic shiners)
What is the most conservative method to control To avoid allergic triggers such as pets
allergic rhinitis symptoms?

Child has a painless blue mass noted on the right Reassurance unless bothersome, then can
lower lip. The child is otherwise healthy, but the consider excision (mucocele)
mother is concerned
A 4-year-old girl presents with unilateral cervical Cat scratch fever—Bartonella henselae
lymphadenopathy, mild fevers; she was scratched
by her new kitten several weeks ago
What is the most common complication of an Hypernasal speech secondary undiagnosed
adenoidectomy? predisposition to velopharyngeal insufficiency
(such as submucosal cleft palate)
CARDIOLOGY
Grace KungAllison Hill, and Jennifer Su
Last-Minute Review—Cardiology Most Likely Answer

Newborn with cyanosis, pulse oximetry changed Cardiac (most likely)
from 60% to 64% only on 100% oxygen
Newborn with cyanosis, pulse oximetry changed Pulmonary (most likely)
from 60% to 88% on 100% O2
What is the reason that left to right shunt lesions The pulmonary vascular resistance drops to
may not present until 1 month of age? normal levels at that time
A 1-day-old infant with a history of maternal Transposition of great vessels
diabetes, cyanosis, and tachypnea, poor response to
supplemental oxygen, loud single second heart
sound, no murmur, chest radiograph shows narrow
mediastinum with small heart tipped on side,
increased pulmonary vascularity
What is the next best step in a newborn with Prostaglandin E1 to keep the patent ductus
suspected transposition of the great vessels? arteriosus (PDA) open, followed by +/− balloon
atrial septostomy and surgery
The most common cause of cyanotic heart disease Transposition of the great vessels
presenting a few days after birth
Newborn presents with cyanosis in the lower Persistent pulmonary hypertension (R→L
extremities, tachycardia, respiratory distress, and shunting across the PDA)
loud single S2 sound
A 1-day-old newborn presents with cyanosis, Tricuspid atresia with pulmonary atresia
single first and second heart sounds, chest
radiograph, shows decreased lung markings, and
electrocardiogram shows left axis deviation
Newborn presents with cyanosis (mother was on a Ebstein anomaly
medicine for severe bipolar disorder), chest
radiograph shows cardiomegaly and right atrial
enlargement
1100 O. I. Naga

Newborn presents with severe cyanosis, systolic Severe pulmonary stenosis
ejection murmur, and a single second heart sound,
chest radiograph shows decreased pulmonary
vascular markings
Newborn presents with intense cyanosis and Supracardiac total anomalous pulmonary venous
respiratory distress, chest radiograph shows a return
“snowman” shaped heart
An 8-week-old boy presents with feeding Tetralogy of Fallot
difficulties, poor weight gain, episodes of bluish
discoloration of the skin while feeding and crying,
a harsh systolic ejection murmur (SEM) is heard
over the pulmonic area and left sternal border;
chest radiograph shows diminished vascularity in
the lungs and diminished prominence of the
pulmonary arteries, a boot-shaped heart (cœur en
sabot)
A 2-year-old with a history of tetralogy of Fallot Hypercyanotic spell (Tet spell)—next step is the
has progressive agitation, increasing cyanosis, and knee-chest position
increased fussiness
During the first 48 h of life, a newborn rapidly Hypoplastic left heart (as PDA closes)
develops cyanosis, tachypnea, respiratory distress,
pallor, lethargy, metabolic acidosis, oliguria, weak
pulses in all extremities, hepatosplenomegaly, and
no murmur
What is the next best step for the newborn in the Prostaglandin E1
previous case with suspected hypoplastic left
heart?
A 2-week-old boy develops congestive heart Coarctation of the aorta
failure, severe metabolic acidosis, and poor
perfusion of the lower extremities
Newborn presents with shock; the echocardiogram Prostaglandin E1
shows coarctation of the aorta. What is the drug of
choice?
A 12-year-old presents with hypertension, Coarctation of the aorta
occasional headache, leg cramps, weak and
delayed femoral pulse, and blood pressure in the
upper limb is higher than the lower limb, chest
radiograph shows rib notching and scalloping on
the undersurface of posterior ribs
A girl with Turner syndrome presents with Coarctation of the aorta
hypertension, weak and delayed femoral pulse
Newborn infant presents with a soft, harsh systolic Peripheral pulmonary stenosis (PPS)
ejection murmur, best heard at the axillae, and
precordium and no symptoms
The most common cardiac lesion associated with Endocardial cushion defect
trisomy 21 (Down syndrome)

The most common cardiac lesion associated with Ventricular septal defect (VSD)
trisomy 18
The most common cardiac lesion associated with Bicuspid aortic valve
Turner syndrome
The most common cardiac lesion associated with Supravalvar aortic stenosis
Williams syndrome
The most common cardiac lesion associated with Branch pulmonary stenosis
Alagille syndrome
The most common cardiac lesion associated with Pulmonary stenosis
Noonan syndrome
The most common cardiac lesion associated with Tetralogy of Fallot
DiGeorge syndrome
The most common cardiac lesion associated with VSD
cri du chat syndrome
The most common cardiac lesion associated with Atrial septal defect (ASD)
Holt–Oram syndrome
The most common cardiac lesion in fetal alcohol VSD, ASD
syndrome
The most common cardiac lesion associated with Ebstein anomaly
lithium teratogen
The most common cardiac lesion associated with Ebstein anomaly
supraventricular tachycardia
The most common cardiac lesion associated with Ventricular hypertrophy
the infant of a diabetic mother
The most common cardiac lesion associated with Cardiac rhabdomyoma
tuberous sclerosis
The most common valvular lesion associated with Mitral regurgitation
acute rheumatic fever
The most common cardiac lesion associated with Aortic root dilation (risk for dissection)
Marfan syndrome
The most common congenital cardiac lesion VSD
overall
The syndrome that is associated with true DiGeorge syndrome
interrupted aortic arch
Adolescent routine physical exam, apical mid- Mitral valve prolapse
systolic non-ejection click, and late systolic
murmur; the murmur is louder when goes from a
supine to a standing position, and the murmur
becomes softer when squatting
Child routine physical exam, systolic murmur with Still’s murmur
a vibratory character, best heard in the lower
sternal border, varies with changes in respiration
and position
A 6-year-old with a continuous murmur, low- Venous hum
pitched sound, best heard in the infraclavicular
region, disappears when supine and with gentle
pressure on the jugular vein
1102 O. I. Naga

While having her hair brushed, a 15-year-old girl Vasovagal syncope
develops cold sweats, pallor, and palpitations and
loses consciousness for 10 s
While running, a 15-year-old girl lost Thorough cardiac evaluation and referral to a
consciousness cardiologist
A 15-year-old girl faints while running and has a Long QT syndrome
positive family history of deafness and sudden
death
The most common cause of sudden cardiac death Hypertrophic cardiomyopathy
in an athlete
Newborn fails hearing screen; EKG shows a very Jervell and Lange-Nielsen syndrome
prolonged QT interval
A 5-year-old, heart rate is 230 beats/min, chest Supraventricular tachycardia (SVT)
discomfort; the heart rate decreases to 80 beats/
min after ice is applied to the face
What is the definitive treatment for SVT? Radiofrequency ablation
Child presents with a history of intermittent Wolff–Parkinson–White syndrome (WPW)
tachycardia; EKG shows a short PR interval,
slurred and slow rise of the initial upstroke of QRS
(delta wave), widened QRS complex
Child presents with chest pain, fever, friction rub; Pericarditis
EKG shows diffuse ST-segment elevation, had
upper respiratory infection 10 days before
Adolescent diagnosed with influenza presents with Myocarditis
fever, tachycardia, edema, and gallop; chest
radiograph shows pulmonary edema, cardiomegaly,
low-voltage EKG
An athlete presents with dyspnea while playing; Hypertrophic cardiomyopathy
systolic ejection crescendo-decrescendo murmur
best heard at the apex and left sternal border, and
radiates to the suprasternal notch; the murmur is
louder while standing and with Valsalva maneuver
A football player presents with chest pain with Restrict from sports then EKG and
exertion and several near syncope episodes during echocardiogram
his football game. Next best step?
EKG in a 12-day-old shows negative T wave in V6 Left ventricular hypertrophy
A 15-year-old boy with a history of recurrent chest Anomalous left coronary artery is most likely
pain during exercise faints and dies while playing
basketball; hypertrophic cardiomyopathy ruled out
as a cause of death. What is the next likely cause?
What is the most common organism responsible Staphylococcus aureus
for infective endocarditis in pediatric patients with
or without congenital heart disease?
History of repaired VSD with a small residual VSD Antibiotic prophylaxis
next to the VSD patch, going in for dental work. Is
subacute bacterial endocarditis (SBE) prophylaxis
indicated?

Child with prosthetic mitral valve going for Antibiotic prophylaxis
surgery; is SBE prophylaxis indicated?
Child with mitral regurgitation and VSD, going in No antibiotic prophylaxis
for dental work. Is SBE prophylaxis indicated?
A mildly desaturated child with tetralogy of Fallot Antibiotic prophylaxis
going in for dental work; is SBE prophylaxis
indicated?
Child with a previous history of endocarditis; is Antibiotic prophylaxis
SBE prophylaxis indicated?
Tall, peaked T waves in precordial leads indicates Hyperkalemia
An infant of diabetic mother presents a few hours Hypocalcemia
after birth with jitteriness, hypoglycemia, cyanosis;
EKG shows prolonged QT interval
EKG shows sinus tachycardia, widened QRS Tricyclic antidepressant (TCA) toxicity
complex with an interval greater than 100 ms, in a
child who presents with altered mental status after
accidentally ingesting grandmother’s medication
EKG shows progressive prolongation of PR Type I second degree AV block (Mobitz I or
interval followed by a drop in QRS Wenckebach)
EKG shows normal PR intervals and periodic drop Type II second degree AV block (Mobitz II)
in QRS
An asymptomatic adolescent with blood pressure Salt restriction in diet
137/87, all labs normal, renal US and chest
radiograph normal. What is the next best step?
A late complication of an untreated ASD or VSD Eisenmenger syndrome—shunt becomes a right
that results in desaturation to left shunt
A 6-month-old infant with failure to thrive, Surgical correction
diaphoresis, and hepatomegaly. Echocardiogram
shows a large VSD. Next best step?
A 4-year-old boy with physical examination Atrial septal defect
significant for widely split and fixed S2 and
crescendo-decrescendo systolic ejection murmur
heard in the second intercostal space at the upper
left sternal border. EKG shows a RSR1 pattern in
V1. What is the most likely diagnosis?
A premature infant with a continuous machine-like PDA
murmur and bounding pulses
Which medication is used to close a PDA in a Indomethacin
premature infant?
What are some common side effects of Thrombocytopenia
indomethacin? GI bleeding
Necrotizing enterocolitis
Renal failure
Systolic murmur most commonly heard at the right Aortic stenosis
upper sternal border radiates to the neck and is
associated with an ejection click
1104 O. I. Naga

Most common valve abnormality associated with Bicuspid aortic valve
aortic stenosis
What is the most likely etiology of an early high- Aortic regurgitation
pitched diastolic murmur associated with bounding
pulses in a patient with Marfan syndrome?
High-pitched holosystolic blowing murmur heard Mitral valve regurgitation
loudest at the apex and radiates to the axilla
Late crescendo systolic murmur associated with a Mitral valve prolapse
mid-systolic click, may be seen in adolescents
Late diastolic rumbling murmur with an opening Mitral valve stenosis
snap heard at the apex
What is the most feared complication of Kawasaki Coronary artery aneurysm
disease?
An 8-year-old presents with sharp stabbing non- Reassurance (precordial catch syndrome)
specific chest pain at rest that resolves shortly.
There are no other symptoms and no past medical
history
A 10-year-old male presents with sharp chest pain; Costochondritis
the pain is reproducible on physical exam
At what ages is lipid screening universally Once between 9 and 11 and again between 17
recommended in the pediatric population? and 21
What is the initial management for an obese Diet and lifestyle modifications, and if
adolescent with elevated cholesterol levels? cholesterol is still elevated after 6 months, then
start statin
PULMONOLOGY
Osama I. Naga
Last-Minute Review—Pulmonology Most Likely Answer

Newborn with inspiratory stridor and noisy Laryngomalacia (usually benign, self-limiting
breathing; stridor improves in the prone position and improves as the child reaches age 1–2 years)
with head elevated and worsens in the supine
position
What is the treatment for laryngomalacia? Reassurance (careful observation and growth
monitoring)
Newborn with a hoarse voice, weak cry, and Unilateral vocal cord paralysis
biphasic stridor that is louder when awake.
Improves when positioned to be lying down on one
side
An infant with bulging anterior fontanelle, high- Bilateral vocal cord paralysis
pitched biphasic stridor, respiratory distress, and
recurrent pneumonia

Adolescent male present with shortness of breath, Vocal cord evaluation. Most likely diagnosis is
choking sensation within a few minutes after paradoxical vocal cord dysfunction
starting track training; there is a voice change
during exercise. He was treated for exercise-
induced asthma with no improvement in his
symptoms. What is the next best step?
Child with a history of chin hemangioma, Subglottic hemangioma
worsening inspiratory stridor
Newborn with intermittent cyanosis that disappears Choanal atresia
when crying but prominent during feeding;
nasogastric tube unable to pass through the nostrils
An infant with cyanosis, the mother is mixing the Methemoglobinemia
formula with well water; normal cardiac and
pulmonary examination, normal pulse oximetry.
Chocolate-colored blood noticed when collecting
the blood for testing
Boy with unilateral persistent offensive smelling Nasal foreign body
nasal discharge
Recurrent pneumonia and nasal polyps Cystic fibrosis
Failure to thrive, rectal prolapse, persistent cough Cystic fibrosis
Sinusitis, bronchiectasis, situs inversus, reduced Kartagener syndrome
male fertility
A 4-year-old boy is suffering from recurrent Primary ciliary dyskinesia
sinusitis, chronic otitis media; during the neonatal
period he had respiratory distress, daily nasal
congestion, and wet cough. What is the most likely
diagnosis?
Child with no known health problem woke up Epistaxis
suddenly coughing blood. What is the most likely
cause?
Child with a 1-day history of low-grade fever, Viral upper respiratory tract infection
malaise, congestion, and very thick, very green
nasal discharge
Child with 2 weeks of clear nasal discharge and a Acute bacterial sinusitis
cough that is worse at night and while lying down
supine. Not responding to nasal allergy
medications
A 7-year-old with fever, runny nose, throat pain; Viral pharyngitis
the pharynx is erythematous and shows white
exudate
A 7-year-old with abrupt onset of fever, headache, Strep throat (Streptococcus pyogenes)
stomach pain, mild throat pain; the pharynx is
erythematous, with petechiae, no white exudates
A 15-month-old boy presents with poor feeding, Streptococcal fever or streptococcosis
high fever, thick, purulent profuse nasal discharge,
crust and irritation around the nostrils
1106 O. I. Naga

When can a child with streptococcal infection go Next day if improved (typically 24 h after the
back to school after taking an antibiotic (become antibiotic)
noninfectious)?
Toddler with a barking cough, fever, inspiratory Croup
stridor, suprasternal retractions, and neck
radiograph is normal
What is the mainstay treatment of croup? Dexamethasone and racemic epinephrine can be
used in moderate/severe cases
A toddler presents with high fever, looks toxic, Bacterial tracheitis
brassy cough, and stridor. He was sent home on
oral antibiotics and ibuprofen, a few hours later he
died
A 5-year-old, unimmunized, presents with sudden Epiglottitis
onset of fever, stridor, drooling and throat pain,
leaning forward and crying
Preschool child has been having recurrent attacks Spasmodic croup or due to GI reflux
of barking cough and croup over the last few
nights, and no symptoms of cough in-between the
attacks
A 3-month-old with fever, cough, runny nose, Acute bronchiolitis
tachypnea and retractions. O/E: wheezing, and
crackles in both lung fields; pulse oximetry is 92%
What is the first-line treatment for bronchiolitis? Nasal suctioning and supportive care
A preterm boy with chronic lung disease is No (discontinue palivizumab for the season)
receiving palivizumab prophylaxis, recovered from
RSV bronchiolitis a few days ago. Can he take his
next due dose of palivizumab?
A 1-month-old infant who was born at 35 weeks Apnea secondary to RSV viral infection
during winter has been having nasal congestion for
the last 2 days; stopped breathing for a few
seconds and turned blue, positive RSV
A 3-week-old with pneumonia; chest radiograph Chlamydia trachomatis
shows bilateral infiltrates
Adolescent with fever, cough, chest pain, shortness Streptococcus pneumoniae
of breath, tachypnea, and pleural friction rub
Adolescent had influenza A infection, now is Staphylococcus aureus pneumonia
having a very high fever, looks toxic; tachypnea,
respiratory distress, and tachycardia; chest
radiograph is positive for infiltration, cavities, and
pleural effusion
A 7-year-old boy has a cough, on and off fever, Mycoplasma pneumoniae
and headache for 2 weeks, on the exam he has
diffuse expiratory wheezing and crackles in both
lung fields with no retractions or tachypnea. Pulse
oximetry is normal. The wheezing is not fully
responsive to nebulized albuterol treatment. What
is the most likely cause?

What is the most helpful diagnostic test in cases of Polymerase chain reaction (PCR) from nasal
atypical pneumonia possibly due to Mycoplasma washing for Mycoplasma antigen
pneumoniae
What is the antibiotic of choice for older children Macrolide antibiotic to shorten the course of
with atypical pneumonia who are ill enough to illness
require hospitalization?
Mississippi and Ohio river valleys, chickens, caves, Histoplasmosis
low-grade fever, cough, hilar lymphadenopathy
Adolescent living in Arkansas presents with Blastomycosis
flu-like symptoms; fever, chills, headache,
myalgia, and cough; 2 weeks later developed
hemoptysis, chest pain, shortness of breath, weight
loss, extreme fatigue, and skin lesions. Chest
radiograph shows a focal mass with well-defined
margins about 6 cm in size in the right upper lobe
and few other focal segmental opacities
Child visited California’s San Joaquin Valley Coccidioidomycosis
3 weeks ago, now has a fever, chills, cough, weight
loss, chest pain, and erythema nodosum. Chest
radiograph is normal
What is the most sensitive serologic test in cases Coccidioides immunoglobulin M (IgM)
with suspected coccidioidomycosis?
History of asthma, recurrent attacks of fever, Allergic bronchopulmonary aspergillosis
fatigue, coughing mucus plugs, hemoptysis,
eosinophilia, high IgE
A sore throat with hoarseness; 3 weeks later Chlamydophila pneumoniae
develops pneumonia
Toddler with a history of choking 2 weeks ago; he Foreign body aspiration
has had a cough since then, wheezing, diminished
breath sounds on the right; normal chest
radiograph
Chest radiograph views that may help in the Inspiratory and expiratory or bilateral decubitus
diagnosis of cases with suspected foreign body views to see asymmetric hyperinflation on the
aspiration side with foreign body due to ball-valve effect
Child with progressive dyspnea, fatigue, recurrent Pulmonary hemosiderosis
cough, new-onset hemoptysis; sputum shows
hemosiderosis-laden alveolar macrophages, and
CBC is consistent with iron deficiency anemia
African-American with shortness of breath, Sarcoidosis
blurring of vision, erythema nodosum,
hypercalcemia, elevated ACE level. Chest
radiograph shows bilateral hilar lymphadenopathy
Child with recurrent episodes of left lower lobe Pulmonary sequestration
pneumonia; chest radiographs demonstrated focal
consolidation in the same location in all events;
between episodes the child is well, active, and
playful
1108 O. I. Naga

Child with fever, chest pain, and productive cough; Bronchogenic cyst
chest radiograph shows cyst-like lesion close to the
mediastinum
An infant has difficulty with feeding, stridor, Vascular ring
recurrent wheezing, history of recurrent
pneumonia. Barium esophagography showed
posterior compressions. What is the most likely
diagnosis?
Asthma > 1 night/week, throughout the day, Severe persistent
extreme limitation of activity, FEV1: < 60%
Asthma 3–4 nights/month, daily, some limitation Moderate persistent
of activity, FEV1 60–80%
Asthma 1–2 nights/month, 3–6 days/week, minor Mild persistent
limitation of activity, FEV1 > 80%
Asthma ≤ 2 days/week, 0 nights/month, no Intermittent
limitation of activity, FEV1 > 80%
Step 1 management of intermittent asthma Short-acting beta agonists (SABA) as needed
Step 2 management of mild persistent asthma Low-dose inhaled corticosteroids (ICS)
Step 3 management of moderate persistent asthma Medium-dose ICS, and consider short course
oral corticosteroids (OCS)
Step 4 management of severe persistent asthma Medium-dose ICS + LABA and consider a short
course of OCS
What is the most effective primary controller ICS
treatment for asthma of any severity?
A 10-year-old boy has shortness of breath and Exercise-induced asthma—use albuterol
cough every time he runs or exercises; positive (bronchodilator) inhaler 15 min before exercise.
family history of asthma; on physical exam the Warm up prior to strenuous activity
lung is clear, the pulmonary function test is
Child with nighttime snoring, enlarged tonsils, and Obstructive sleep apnea
difficulty concentrating in school
NUTRITION
Susan S. Baker
Last-Minute Review—Nutrition Most Likely Answer

Xerophthalmia, corneal opacity, bitot spots, night Vitamin A deficiency
blindness, growth failure, and recurrent infection
Gingival bleeding, anemia, corkscrew-coiled hairs, Vitamin C deficiency
anorexia, and irritability
Breastfed children should be supplemented with Vitamin D
which vitamin from birth?
Last-Minute Review—Nutrition Most Likely Answer

Child with a history of cystic fibrosis presents with Vitamin E deficiency
ataxic gait, diminished deep tendon reflexes in the
lower extremities, as well as generalized weakness
in the lower extremities
Vitamin that affects prothrombin, factor VII, factor Vitamin K
IX, factor X
Child is receiving a prophylactic antibiotic for the Vitamin K deficiency
last few months. Prothrombin time (PT) and partial
thromboplastin time (PTT) are mildly prolonged
Foot and wrist drop, ataxia, ophthalmoplegia, Vitamin B1 deficiency (thiamine)
confusion, abnormal sensation, heart failure,
dyspnea, and edema
Redness and fissuring of lips (cheilitis), soreness of Vitamin B2 deficiency (riboflavin)
tongue, anemia, fatigue
Diarrhea, dementia, dermatitis, and death in severe Vitamin B3 deficiency (niacin)
cases
Which vitamin is needed to supplement a child on Vitamin B12 (other supplements to consider:
a strict vegan diet? iron, zinc, and calcium)
The site of vitamin B12 absorption Ileum
Infant drinks goat’s milk, looks pale, CBC shows Folic acid deficiency
macrocytic anemia
Acute illness with diarrhea, fever, and vomiting for Lactose-free diet and lactase supplement (lactose
2 days, followed by persistent diarrhea for intolerance)
3 weeks, 6–9 episodes of liquid stools without
visible blood or mucus, associated with
generalized abdominal pain, distended and
flatulent since the acute illness. A positive reducing
substance in the stool. What is the best
management?
Taste and smell impairment, night blindness, and Zinc deficiency
depressed immunity
Deficiency associated with recurrent diarrhea, Zinc deficiency
alopecia, and rash (acrodermatitis enteropathica)
Child previously healthy is living with stepfather, Marasmus and possible calorie deprivation
generalized loss of muscle mass, and no
subcutaneous fat
Child lives in a shelter, poor nutrition, failure to Kwashiorkor (protein-energy malnutrition)
thrive, weakness, edema, moon facies, a swollen
abdomen (potbelly), dark, dry skin, with pale areas
between the cracks, depigmentation of hair, and
fatty liver
1110 O. I. Naga
GASTROENTEROLOGY
Robert D. Baker
Last-Minute Review—Gastroenterology Most Likely Answer

An exclusively breastfed infant has not stooled Reassurance (breastfed infants may go several
for 5 days with no other symptoms. The stool is days or even a week between bowel movements)
soft with no rectal bleeding. The infant is gaining
weight
A 1-week-old child with frequent spit-ups, Reassurance (newborn reflux is normal)
otherwise doing well
What are the upper GI series useful for? To rule out anatomic or motility problems. Does
not diagnose reflux
A 3-week-old first newborn boy presents with Pyloric stenosis
nonbilious projectile vomiting, hypochloremic,
hypokalemic metabolic alkalosis, and dehydration
What is the next best step in cases with suspected Abdominal US (pylorus)
pyloric stenosis?
Weight loss, abdominal pain, nausea, effortless Rumination syndrome
postprandial regurgitation after at least 1 meal
daily for 1 month, regurgitated food occasionally
reswallowed, rechewed, or spit out
Child with no known health problem woke up Epistaxis (nose bleeding is the most common
suddenly vomiting blood. The child is stable and source in healthy children)
acting normal. What is the most likely cause?
Nausea and vomiting every 1–2 months, each Cyclic vomiting syndrome
episode lasts for few hours, otherwise healthy, no
symptoms in-between episodes, positive family
history of migraine
A 7-year-old healthy child, with periumbilical Reassurance (functional abdominal pain)
abdominal pain worse in the morning prior to
school, improves during weekends with normal
growth parameters
High achieving adolescent complains of crampy Irritable bowel syndrome
abdominal pain, diarrhea, and at other times,
constipation; pain is relieved with stooling
Adolescent presents with recurrent episodes of Peppermint oil, diet modifications, cognitive
abdominal pain, diarrhea, and sometimes behavioral therapy
constipation in the previous 3 months. No weight
loss and all labs are normal. What is the best
treatment?
A mother brought her toddler with a diaper full of Toddler diarrhea
undigested food, the child is holding a large bottle
of apple juice
The best management of toddler’s diarrhea Juice restriction and allow normal dietary fat
Child with a low-grade fever, 6 episodes of Oral rehydration therapy (avoid anti-diarrheal
diarrhea, otherwise reassuring medical exam. agents)
What is the treatment of choice?

What is the major concern of using antimotility May induce ileus
drugs such as Loperamide?
An infant presents with bright red blood stool, Cow milk protein intolerance
poor weight gain, diarrhea, and fussiness; the
infant is breastfeeding, supplemented with
standard infant formula; stool guaiac test is
positive
Child with dysphagia, recurrent food impaction; Eosinophilic esophagitis
biopsy shows an increased eosinophil?
Adolescent with recurrent headaches takes Pill-induced esophagitis
ibuprofen as needed, presents with dysphagia and
chest discomfort (does not like to drink water
with medicine)
Child accidentally swallowed caustic liquid 6 h Endoscopy in 12–24 h after ingestion
ago, presents with dysphagia, oral pain, chest
pain, nausea, and vomiting
Swallowed a coin, no symptoms, and radiograph Observe for 12–24 h, removal of the coin if it
showed the coin still in the esophagus does not pass to the stomach or if the patient
became symptomatic
Swallowed a coin, no symptoms, and radiograph Checking the stool for passage for 4 weeks, with
showed the coin in the stomach weekly radiographs, if indicated
4 weeks passed and the coin still in the stomach If the coin does not pass through the stomach by
with no symptoms 4 weeks or if the patient is symptomatic, removal
by endoscopy should be considered
Swallowed a coin, excessive drooling, and chest Immediate removal
pain, and radiograph showed the coin still in the
esophagus
Swallowed a button battery (BB), and passed to Immediate removal
the stomach with symptoms
Swallowed a BB, and passed to the stomach Urgent removal (if age < 5 and BB ≥ 20 mm)
without symptoms Elective if not moving (checking the stool for
passage for 4 weeks, with weekly radiographs)
Swallowed a BB that got stuck in the esophagus Immediate removal
Swallowed small pieces of magnet metals; the Immediate removal
abdominal radiograph showed the pieces in the
stomach
An older child with bloating, constant burping, Helicobacter pylori infection
sharp epigastric pain that awakens the child from
sleep
The most common cause of chronic gastritis in H. pylori
pediatrics
The best and most definitive test for peptic ulcer Endoscopy
disease
What is the treatment of H. pylori infection? Amoxicillin or metronidazole + clarithromycin +
PPI for 2 weeks
1112 O. I. Naga

Infant suddenly develops bilious vomiting, Upper GI series with follow through
abdominal distension, tenderness, and fussiness.
What is the diagnostic test of choice?
In the infant above, the GI series shows a bird’s Volvulus
beak sign of the second portion of the duodenum
Intermittent crampy abdominal pain, lethargy, Intussusception
bilious vomiting, and a palpable mass in the right
upper quadrant
What is the best initial diagnostic test of choice in Abdominal US (target sign, reflecting a segment
cases of intussusception? of bowel trapped within a distal segment of
bowel)
What is the therapeutic procedure of choice in Air contrast enema (diagnostic and therapeutic)
cases of intussusception?
Down syndrome, bilious vomiting, double bubble Duodenal atresia
sign on KUB
A mother brought her 9-month-old girl with a Most likely the medicine, e.g., cefdinir may
diaper full of red, maroon stool; the physical change the stool color to maroon color (blood-
exam is normal, and the infant is feeding well and like color)
smiling (she is receiving an antibiotic for AOM)
A 2-year-old boy, frank rectal bleeding, anemia, Meckel diverticulum
no pain, no other symptoms
What are the 2 most common ectopic tissues Gastric and pancreatic
found in Meckel diverticulum?
How is Meckel diverticulum diagnosed? Technetium 99 scan
Infant, failure to thrive, rectal prolapse Cystic fibrosis
Most common cause of rectal prolapse in the Constipation
USA
Rectal bleeding, large and hard stool in the diaper Anal fissure
The most common cause of rectal bleeding in Anal fissures
infants
A 2-year-old boy with chronic constipation, Hirschsprung disease
ineffective laxatives, fails to pass meconium in
the first 48 h of life, explosive stools on rectal
exam, KUB showed very distended colon
A 48-h old boy did not pass the meconium; the Hirschsprung disease
abdomen is slightly distended
Most accurate diagnostic test for Hirschsprung Full-thickness rectal biopsy performed by surgery
disease
Persistent epigastric abdominal pain, vomiting; Acute pancreatitis
the pain is referred to the back, tenderness in the
epigastric region, elevated amylase, and lipase
enzymes
Child with Down syndrome, intermittent Celiac disease
abdominal pain, and failure to thrive
Child with type 1 diabetes mellitus and recurrent Celiac disease
abdominal pain

Child with a history of recurrent abdominal pain Ulcerative colitis
presents with fever, abdominal pain, bloody
diarrhea, migratory arthritis, erythema nodosum,
ankylosing spondylitis, elevated ESR, positive
P-ANCA
Recurrent aphthous ulcers, abdominal pain, Crohn’s disease
weight loss, perianal lesions, positive anti-
Saccharomyces antibodies
Jaundice, abdominal pain, and fever Cholangitis
Jaundice, abdominal pain, and a palpable mass in Choledochal cyst
the right upper quadrant
Hydrops of the gallbladder can be seen in Kawasaki disease
Conditions associated with an increased incidence Sickle cell anemia, chronic total parenteral
of cholelithiasis nutrition (TPN), adolescent pregnant females
What is the most common complication of Pancreatitis
cholelithiasis?
A 3-year-old boy presents with failure to thrive, Creatinine phosphokinase (CK) (muscular
difficulty walking; the metabolic panel shows dystrophy most likely)
elevated aspartate transaminase (AST) and
alanine transaminase (ALT). Total bilirubin,
prothrombin time, blood glucose, TSH and free
T4 are all normal, negative hepatitis viral panel.
What is the test of choice in this case?
What are the sources of transaminases (ALT and Liver, heart, muscles, kidney, and brain
AST)? It is important to consider other sources of
transaminases if they are elevated and the liver
function is normal
The best laboratory test for acute hepatitis A Anti-HAV IgM
A mom is asking about prophylaxis for her Administer IG as prophylaxis (< 1 year)
4-month-old child after she was recently
diagnosed with hepatitis A?
Prophylaxis of a 3-year-old child exposed to a Hepatitis A vaccine (> 1 year)
documented case of hepatitis A in a child care
center
All hepatitis viruses are composed of RNA except Hepatitis B virus is composed of DNA
Which virus infection must have hepatitis B? Hepatitis D
Child with a family history of lupus disease Autoimmune hepatitis
presents with jaundice, hepatomegaly, weight
loss, loss of appetite, positive anti-smooth muscle
antibodies
One week with jaundice, hepatomegaly, slightly Acute hepatic failure
elevated ALT and AST, prolonged PT that is not
responding to IV vitamin K, and recurrent
hypoglycemia
1114 O. I. Naga

An 8-year-old boy has recurrent jaundice, slightly Gilbert syndrome
elevated indirect bilirubin; physical examination
and all other labs are normal
A 1-day-old boy with intense jaundice, Crigler–Najjar syndrome type I (exchange
unconjugated bilirubin is 25 mg/dL, and no transfusion is warranted)
conjugated bilirubin; and poor response to
phototherapy
Mild conjugated hyperbilirubinemia with black Dubin–Johnson syndrome
liver
An infant with jaundice, dark urine, light-colored Biliary atresia
stool, hepatomegaly, and elevated conjugated
bilirubin
What is the most valuable study for neonatal Percutaneous liver biopsy
biliary atresia?
If liver biopsy confirmed biliary atresia, what is Intraoperative cholangiography
the next appropriate test?
Adolescent presents with depression, psychosis, Wilson disease
and elevated liver enzymes
Which mineral is affected in Wilson disease? Copper (excess)
How to establish the diagnosis of Wilson disease Ceruloplasmin < 20 mg/dL. Hepatic copper
> 250 ug/g dry weight. Urine copper
> 100 ug/24 h. Presence of Kayser–Fleischer
rings
Broadened forehead, jaundice, pulmonary Alagille syndrome
stenosis, and butterfly hemivertebrae
Abdominal mass, elevated liver enzyme, and high Hepatoblastoma
serum alpha-fetoprotein
A 3-month-old, failure to thrive, extreme pruritus, Progressive familial intrahepatic cholestasis
steatorrhea, very high-conjugated bilirubin, (PFIC) type 1
hepatosplenomegaly, mutilated skin, elevated
serum alkaline phosphatase, and normal gamma-
glutamyl transferase (GGT)
Prognosis of all forms of PFIC Lethal during childhood unless treated early
Hematochezia, intestinal polyp, pigmented penile Bannayan–Riley–Ruvalcaba syndrome
lesion, large head, café-au-lait spots, intellectual
disability
> 5 juvenile polyps Juvenile polyposis
What is the next step in children with ≥ 5 Genetic testing
juvenile polyps or any number of adenomatous
intestinal polyps?
100 or more adenomatous polyps in the large and/ Familial adenomatous polyposis
or small intestines
Intestinal polyps, osteoma of the mandible, Gardner syndrome
papillary carcinoma of thyroid, and
hepatoblastoma
Intestinal polyps and brain tumor Turcot syndrome

Intestinal polyps, hematochezia, mucocutaneous Peutz–Jeghers syndrome (increases the risk of
freckling, and a family history of polyposis cancer)
Hamartomas involving many areas of the body, Cowden syndrome
e.g., skin, oral mucosa, thyroid, breast, and colon
Associated risks of Cowden syndrome Cancer, e.g., thyroid cancer
Hemihypertrophy, very large extremities, Proteus syndrome
epidermal nevus, hamartomatous polyps,
intellectual disability
Potential risks of Proteus syndrome Deep vein thrombosis (DVT) and
thromboembolism
The best diagnostic test for lactose intolerance Hydrogen breath test
NEPHROLOGY
Beatrice Goilav
Last-Minute Review—Nephrology Most Likely Answer

A 5-year-old hospitalized and receiving penicillin IV Antibiotic-induced allergic interstitial
for 10 days, developed rash, eosinophilia, nephritis
eosinophiluria, pyuria (sterile), hematuria, moderate
proteinuria (usually < 1 g/day)
A 4-year-old had throat infection 2 weeks ago, tea- Postinfectious glomerulonephritis
colored urine, BP is slightly elevated, RBC casts in
urine, low C3 and normal C4
History of impetigo, tea-colored urine, hypertension, Postinfectious glomerulonephritis
periorbital edema, C3 is low, normal C4, azotemia,
normal ASO titer, positive anti-DNAse, oliguria, and
RBC casts in urine
Low C3 and cola-colored hematuria (RBC casts) Postinfectious glomerulonephritis
2–3 weeks after upper respiratory tract infection
Normal C3 and episodic gross hematuria (RBC casts) IgA nephropathy
during acute upper respiratory tract infection
The most common cause of gross hematuria in IgA nephropathy
children
Can antibiotics prevent acute postinfectious No
glomerulonephritis?
Can antibiotics prevent acute rheumatic fever? Yes
After poststreptococcal glomerulonephritis (PSGN) No—at least 6 weeks before C3 levels return
does the C3 level normalize immediately after the to normal
illness?
Are steroids indicated in PSGN? No—only supportive care measures and BP
control as needed
1116 O. I. Naga

Adolescent female with rapidly progressive Lupus nephritis
glomerulonephritis, hypertension, and both C3 and C4
are decreased
A healthy child with proteinuria, morning specimen is Benign orthostatic proteinuria
negative for proteinuria
A 3-year-old, swelling of the face and generalized Nephrotic syndrome due to minimal change
edema, normal blood pressure, 4+ proteinuria, no disease
hematuria, hyperlipidemia, hypoalbuminemia, normal
C3 and C4, urine is negative for protein after 3 weeks
of steroid therapy
Child with nephrotic syndrome not responding to Focal segmental glomerulosclerosis
treatment and progressing to chronic kidney disease
Adolescent with nephrotic syndrome, microscopic Focal segmental glomerulosclerosis
hematuria, and hypertension
Adolescent presents with proteinuria, hematuria, Membranoproliferative glomerulonephritis
hypertension, persistent low C3, hyperlipidemia, renal
failure
Child presents with persistent proteinuria, history of Membranous glomerulonephritis
hepatitis B virus infection
Child develops acute kidney injury and within 4 weeks Rapidly progressive (crescentic)
progresses to end-stage renal disease, renal biopsy glomerulonephritis
shows crescents formation in most glomeruli
Which serologic marker can be positive in rapidly P-ANCA
progressive glomerulonephritis?
A 5-year-old has blood in urine, urine is positive for Familial thin basement membrane
hematuria, RBC casts, renal function is normal, no nephropathy (autosomal dominant)
hypertension, positive family history of hematuria with
every generation affected
Microhematuria, proteinuria, absent patella, dystrophic Nail-patella syndrome (autosomal dominant)
nails, dysplasia of elbows
A 7-year-old, failure to thrive, polyuria, polydipsia, Juvenile nephronophthisis
anemia, ocular apraxia, retinitis pigmentosa,
coloboma, nystagmus, aplasia of the cerebellar vermis,
loss of differentiation between cortex and medulla on
renal US
Boy with a sensorineural hearing loss, proteinuria, Alport syndrome (X-linked disease)
mother’s brother died from renal failure
Upper respiratory infection a week ago, now with Henoch-Schönlein purpura
petechiae on the buttocks and lower extremities,
abdominal pain, arthralgia, and hematuria
Bloody diarrhea, which resolves, but then the child Hemolytic uremic syndrome
becomes pale and tired and is found to have hemolytic
anemia, thrombocytopenia, elevated BUN and
creatinine. A stool culture is positive for Escherichia
coli (E. coli) O157: H7

The most common causes of oliguric acute kidney Nephrotoxins and rhabdomyolysis
injury requiring dialysis in children
Child on amphotericin B developed kidney stones, and Renal tubular acidosis (RTA) type 1
blood work showed non-anion gap metabolic acidosis.
Child with polyuria, polydipsia, dehydration, growth Fanconi syndrome
failure, non-anion gap metabolic acidosis,
hypokalemia, hypophosphatemia, proteinuria,
glucosuria
Type of renal tubular acidosis associated with Fanconi RTA type 2
syndrome
Type of renal tubular acidosis associated with RTA type 4
hyperkalemia
Hemoptysis, hematuria, proteinuria, positive anti- Goodpasture syndrome
glomerular basement membrane antibodies
(anti-GBM)
Child on Lasix, presents with oliguria, elevated Prerenal acute kidney injury
creatinine; urine osmolality is > 400 mOsm/L, urine
Na < 20, FeNa < 1%, urine is positive for hyaline cast
Child after a car accident and crush injury presents Acute tubular necrosis (intrarenal acute
with high BUN/Cr, oliguria, urine osmolality kidney injury)
300 mOsm/L. FeNa > 1%, urine Na > 20, large muddy
brown granular cast
A male infant with posterior urethral valves, born Postrenal acute kidney injury
prematurely and is found to have high BUN/Cr,
elevated FeNa, normal urine osmolality, elevated urine
Na
Status post-cardiac arrest, BUN and creatinine are Acute tubular necrosis secondary to ischemia
elevated, hyperkalemia, hyponatremia,
hyperphosphatemia, hypocalcemia, urine shows
muddy brown, and granular casts
Adolescent with severe muscle cramps, numbness, low Gitelman syndrome (metabolic alkalosis and
blood pressure, fatigue, metabolic alkalosis, high urine chloride, low serum Mg, and low
hypochloremia, hypokalemia, hyponatremia, urine Ca)
hypomagnesemia, polyuria, low urine calcium, and
high urinary chloride 70 mEq/L. High aldosterone and
renin levels
An infant with failure to thrive, dehydration, low blood Bartter syndrome (metabolic alkalosis and
pressure, metabolic alkalosis, hypochloremia, high urine chloride, normal serum Mg, and
hypokalemia, hyponatremia, normal serum magnesium normal or high urine Ca)
level, polyuria, normal urine calcium, and high urinary
chloride 70 mEq/L. High aldosterone and renin levels.
High urinary prostaglandin level
1118 O. I. Naga

Child with a positive family history of hypertension Liddle syndrome (autosomal dominant)
(parents) presenting with headache, hypertension,
hypokalemia, metabolic alkalosis, and high urinary
chloride
Adolescent with mild glomerulonephritis, history of Churg Strauss syndrome
allergies/asthma with elevated eosinophil levels on
CBC
An older child with a prolonged history of fever, Granulomatosis with polyangiitis (formerly
weight loss, hematuria, and hemoptysis. Radiograph Wegner granulomatosis)
shows necrotizing granuloma and C-ANCA positive
A young child with palpable kidneys bilaterally, Autosomal recessive polycystic kidney
hypertension, and associated with a history of disease
oligohydramnios
The predominant type of polycystic kidney disease Autosomal dominant polycystic kidney
seen in adults disease
How is hypertension defined in children? BP > 95th percentile for age, height, and
gender on 3 different occasions or greater
than 130/90 mmHg in children aged 13 years
and older
How is elevated blood pressure defined in children? BP ≥ 90th (≥ 13 years BP > 120/80 mmHg
matching new adult guideline)
Adolescent with severe muscle weakness after Rhabdomyolysis—heme positive urine but
exercise, hypophosphatemia, hypokalemia and no RBC
elevated CPK with myoglobinuria
Child with nausea, severe flank pain, and hematuria Renal stone
The most common type of stones in children Calcium oxalate
Type of kidney stone associated with staghorn calculi Struvite stones
and Proteus?
Type of stone associated with an autosomal recessive Cystine stones
pattern
First-line therapy for children with primary Bedwetting alarm and desmopressin (both)
monosymptomatic nocturnal enuresis
Recommended lifestyle changes in all cases of Adequate hydration during the day
monosymptomatic nocturnal enuresis Limit fluids before bed (≤ 200 mL)
Void before bed
Regular sleep and wake schedule
Diurnal enuresis after continence Requires prompt evaluation
FLUIDS AND ELECTROLYTES
Beatrice Goilav
Last-Minute Review—Fluids and Electrolytes Most Likely Answer

Low urinary fractional excretion of sodium, high Dehydration
urine osmolality, high serum osmolality
High urinary fractional excretion of sodium, low Syndrome of inappropriate ADH secretion
serum sodium, low serum osmolality, (SIADH)
inappropriately high urine osmolality
Low urine osmolality, high serum sodium, and Diabetes insipidus
serum osmolality (urine osmolality < serum
osmolality)
Low serum and urine osmolality Primary polydipsia
Child with mild to moderate dehydration because Oral rehydration solution (ORS)
of diarrhea, able to drink with no emesis. What is
the best treatment?
What is the mechanism of action of ORS? Sodium-glucose transporter in the gut
(co-transports one sodium with one glucose)
Child with moderate dehydration, no emesis, and ORS and oral K chloride supplementation (oral
low serum potassium (K) level 2.6 mEq/L. No replacement is better than IV if tolerating oral
other symptoms. What is the best treatment? intake)
Child with vomiting, weakness, lethargy, IV bolus 20 ml/kg normal saline, then IV fluids
moderate-severe dehydration, and low serum and electrolyte replacement
potassium (K) level 2.6 mEq/L. What is the best
treatment?
Based on the Holliday-Segar method, what is the First 10 kg × 4 = 40
maintenance fluid rate for 45 kg child? 2nd 10 Kg × 2 = 20
25 kg × 1 = 25
40 + 20 + 25 = 85 ml/h
A 12-month-old girl with 4 days of frequent D5 ½ NS +KCl 40 meq/L to run at 95 mL/h
watery stool; she is listless. O/E: dry mucous (15% dehydration; fluid deficit is 1500 + 1000
membrane, skin is tenting, HR 150, BP (maintenance—200 (bolus) = 2300/24 h =
85/45 mmHg. Weight 8.5 kg. Weight before illness 95 ml/h)
10 kg, serum Na 136 mEq/dL. 200 mL of NS given
IV. What is the most appropriate IV fluid and rate
for this child?
A 12-month-old girl with 4 days of frequent D5 ½ NS + KCl 40 meq/L to run at 116 mL/h
watery stool, she is listless. O/E: dry mucous (20% dehydration; fluid deficit is 2000 + 1000
membrane, skin is tenting, HR 170, BP (maintenance—200 (bolus) = 2800/24 h =
80/40 mmHg. Weight 8 kg. Weight before illness 116 ml/h)
10 kg, serum Na 136 mEq/dL. 200 mL of NS given
IV. What is the most appropriate IV fluid and rate
for this child?
A quick calculation in the previous case? The maintenance rate for a 10 kg child = 40 ml/h
→ triple the maintenance rate in 20%
dehydration → 120 ml/h (close to 116)
1120 O. I. Naga
Last-Minute Review—Fluids and Electrolytes Most Likely Answer

A quick calculation of IV fluid rate in 5% 1½ times the maintenance rate
dehydration
A quick calculation of IV fluid rate in 10% Double the maintenance
dehydration
A quick calculation of IV fluid rate in 15% 2 ½ times the maintenance rate
dehydration
What is the advantage of ORS over other fluid Low carbohydrate, high sodium and potassium
options? (minimizing osmotic loads that drive more
diarrhea)
What is a normal anion gap? Na+ – (Cl– + HCO3–) = 10–12 mEq/L
What are the causes of anion gap metabolic Methanol poisoning, Uremia, DKA,
acidosis? Paraldehyde, Iron toxicity, INH, Lactic acidosis,
Ethylene glycol, Salicylate poisoning (MUD
PILES)
What are the causes of non-anion gap metabolic Renal tubular acidosis
acidosis? Diarrhea
Chronic total parenteral nutrition (TPN)
Acetazolamide (carbonic anhydrase inhibitor)
A 3-week-old boy with projectile vomiting after Pyloric stenosis (metabolic alkalosis and low
each feed, dehydration, metabolic alkalosis, urine chloride)
hypochloremia, hypokalemia, oliguria, and low
urinary chloride (< 20 mEq/L)
Child with bloody diarrhea, high fever, weakness, Intravenous calcium gluconate, glucose, and
edema, oliguria, BUN 80 mg/dL, creatinine 5 mg/ insulin, beta agonists, cation exchange resins
dL, K level is 7.5 mg/dL. EKG shows a widening (sodium polystyrene sulfonate), until dialysis
of QRS complexes and an increased PR interval. can be initiated
What is the earliest EKG manifestations in cases of Tall and peaked T waves
mild hyperkalemia?
What is the EKG manifestation in cases of Widening of QRS complexes and an increased
moderate hyperkalemia? PR interval
What is the EKG manifestation in cases of severe Broad and low amplitude P waves, a prolonged
hyperkalemia? QT interval, and ST-segment changes (elevation
or depression)
What is the EKG manifestation of hyperkalemia Gradually widening QRS complexes and absent
> 8 mEq/L? P waves → ventricular fibrillation or asystole
UROLOGY
Osama I. Naga
Last-Minute Review—Urology Most likely Answer

Newborn with prenatal ultrasound (US) positive Renal US after 48 h of life
for hydronephrosis (> 10 mm AP diameter of the
renal pelvis. What is the next best step?

What is the best test to confirm the diagnosis of Urine culture
urinary tract infection (UTI)
A one-year-old child presents with the first febrile Renal-bladder US (RBUS)
UTI. What is the appropriate imaging study?
What is the gold standard test for the diagnosis of Voiding cystourethrography (VCUG). It should
anatomical details of the renal system and degree not be routinely performed in children after a
of reflux? first febrile UTI
What are the indications of VCUG? Findings on RBUS that suggest the presence of
high-grade vesicoureteral reflux or the
recurrence of febrile UTIs
What is the main difference between cystitis and Presence of fever and urine infection is highly
acute pyelonephritis? suggestive of pyelonephritis
Prevalent cause of recurrent UTIs in children Constipation
Child with an indwelling catheter and a urine Enterococcal UTI
dipstick analysis negative for nitrites
Empiric antibiotics in patients suspected of having Combination of ampicillin or amoxicillin and,
an enterococcal UTI third-generation cephalosporin or
aminoglycoside
A 4-year-old boy with weak urine stream, failure VCUG for the possibility of a posterior urethral
to thrive, recurrent UTIs, enuresis. The renal US is valve
positive for bilateral hydronephrosis. What is the
best test to establish the diagnosis?
A 4-year-old female with a history of chronic Female urethral prolapse
constipation presenting with vaginal bleeding and
urethral mass
A 6-year-old female with persistently damp Ectopic ureter
underwear (day and night)
A 7-year-old uncircumcised boy with penile pain, Emergent reduction of the foreskin to its
swollen foreskin O/E: head of the penis is enlarged anatomical position. May apply compression,
and congested with a collar of edematous foreskin. sugar, pin-pricks to decrease the edema
A constricting band of retracted foreskin is noted
past the head of the penis. What is the best
treatment?
What are the most common anatomical Hypospadias with incomplete foreskin,
contraindications of circumcision? epispadias, ambiguous genitalia
An uncircumcised 3-year-old boy presents with a Reassurance (normal smegma)
nonpainful, white, mobile mass just distal to the
corona of the boy’s penis
Full-term male newborn presents with right Referral to a surgeon if the testis remains
undescended testis. The remainder of the physical undescended at 6 months of age
examination is unremarkable. What is the next best
step?
A 15-year-old boy presents with a painless, solid, Testicular cancer until proven otherwise
firm, irregular mass in the left testicle
A 12-year-old boy presents with sudden onset of Testicular torsion
testicular pain, vomiting, the right testicle is
swollen, tender, absent cremasteric reflex
1122 O. I. Naga

Patient presents with testicular torsion Immediate urology consult (the testicular US
should not delay the consultation)
A 12-year-old boy presents with pain, tenderness, Torsion of the testicular appendage
and swelling in the upper pole of the right testicle.
O/E: bluish dot is visible through the scrotum
A 12-year-old boy presents with soft non-tender Hydrocele
fullness within the left hemiscrotum, homogenous
glow without internal shadows on
transillumination; testes are palpable posteriorly
An 18-year-old male presents with a left-sided Varicocele
mass that feels like a bag of worms; the left testicle
is smaller than normal; the mass increases in size
with Valsalva maneuver
Adolescent male is complaining about a mobile Spermatocele
nodule noted above the testis; the mass does not
increase with Valsalva
A sexually active adolescent male presents with Epididymitis
testicular pain that improves with testicular
elevation; he has dysuria and fever. The
cremasteric reflex is intact
A 10-year-old boy with a sudden onset of right Pain medicine, aggressive hydration (most
flank colicky abdominal pain, nausea, vomiting, stones smaller than 5 mm pass spontaneously in
frequent urination. Physical examination is normal. children)
The urine test is positive for 20 RBCs. The renal
US shows 3 mm stone in the right ureter
A 10-year-old boy presents with blood in urine and Urethral injury (best study is retrograde
difficulty voiding after blunt trauma to the genital urethrography)
area. O/E: there is a drop of blood on the meatus
DERMATOLOGY
Last-Minute Review—Dermatology Most Likely Answer

Pustules of erythema toxicum contain Eosinophils (reassurance)
Pustules of transient neonatal pustular melanosis Neutrophils (reassurance)
contain
Newborn with white papules on the hard palate Epstein pearls (reassurance)
Newborn with pinhead white papules on the face Milia (reassurance)
Newborn with white papules on the upper gums Bohn nodules (reassurance)
An infant with small papules and pustules on the Neonatal acne (resolves without treatment)
forehead, nose, and cheeks and an absence of
comedones.

Newborn with blistering and erosions of the skin. Epidermolysis bullosa
May have mucous membrane and nail
involvement. Infection has been ruled out
What is the best diagnostic test for epidermolysis Skin biopsy of an induced blister or genetic
bullosa? testing
Well-defined erythematous plaques on the knees Psoriasis
and elbows, covered with silvery scales, bleed
when removed, pitting of the nails
Child with ulcerative colitis presents with bright Erythema nodosum
red, tender nodules on the anterior leg
Erythematous, scaly plaques in periorificial and Acrodermatitis enteropathica (zinc deficiency)
acral areas, alopecia, and diarrhea
A 2-year-old boy with fever, fragile blisters, and Staph scalded skin syndrome (SSSS)
denuded skin, predominantly affecting the flexures
and perioral skin
Adolescent boy with a history of cold sores Erythema multiforme
presents with targetoid papules, distributed acrally,
and hemorrhagic crusting of the lips
Child is taking penicillin for a dental abscess, Stevens–Johnson syndrome
developed macules, papules, vesicles, bullae, and
ulcerations on 8% of the body surface area.
Sloughing, blistering, and ulceration around the
lips, eyes, and genitalia are also present
Most common virus that triggers erythema Herpes simplex virus (HSV)
multiforme
Poorly defined, hypopigmented rough macules and Pityriasis alba
patches on the cheeks
Adolescent with oval scaly papules and plaques on Pityriasis rosea
the trunk that run parallel to skin cleavage lines
Adolescent boy with hypopigmented scaly lesions Tinea versicolor
on the neck, chest, and back that worsen with sun
exposure
What is the cause of tinea versicolor? Malassezia furfur
Child with an itchy rash affecting both feet. Exam Topical antifungal cream, e.g., terbinafine cream
shows scaling, fissuring, and maceration in the
interdigital spaces. What is the best treatment?
Child with one bald spot on the scalp with scale Oral antifungal
and “black-dot” hairs (the remnants of broken hairs
within follicles). What is the best treatment?
Child with one bald spot on the scalp with no Reassurance or topical steroids (alopecia areata)
associated scale or redness. What is the best
treatment?
A young child with diffuse thinning of the hair on Telogen effluvium
the scalp after undergoing major surgery 3 months
prior
1124 O. I. Naga

Condition with pegged-shaped teeth, prominent Hypohidrotic ectodermal dysplasia
ears, small chin, frontal bossing, absence of
sweating with associated overheating
Female neonate with blistering and/or Incontinentia pigmenti (X-linked dominant)
hyperpigmentation of the skin in a blaschkoid
distribution. May be associated with eye and
neurologic abnormalities
Fish-like scaling of the body, sparing flexural X-linked recessive ichthyosis
areas, with corneal opacities and history of
cryptorchidism
Extremities are covered with fine, irregular, Ichthyosis vulgaris
polygonal scales, hyperlinear palms; worse with
dry weather and during winter, family history of
“dry skin”
Erythematous, scaly, itchy plaques in the Atopic dermatitis
antecubital and popliteal fossae, older brother with
asthma
A 3-year-old boy was exposed to poison ivy while Topical steroids (Rhus dermatitis)
playing in the garden. He developed itchy linear
streaks of vesicles on both arms. What is the best
treatment?
What is the most important recommendation for all Avoidance of triggering agents
cases of contact dermatitis?
Folliculocentric papules with central keratinous Keratosis pilaris
debris on the upper arms and thighs
Unilateral, irregular brown to blue-gray Nevus of Ito
pigmentation of the neck, shoulder,
supraclavicular, deltoid, and/or upper arm skin.
May darken at puberty
Unilateral, irregular, blue-gray discoloration in the Nevus of Ota
periorbital area and sclera (Ocular)
A nevus of Ota involving the sclera requires Glaucoma > ocular melanoma
monitoring by ophthalmology due to increased risk
of
Large congenital nevi likely carry an increased risk Melanoma
of what type of cancer?
Child is going to the beach for swimming and Apply SPF 30 or greater sunscreen 15–30 min
parents are concerned about sunburn. How would before sun exposure, reapply every 2 h
you counsel the family about sunscreen use?
Large facial port-wine stain involving V1, seizures, Sturge–Weber syndrome
and glaucoma
Posterior fossa malformations (Dandy–Walker), PHACE syndrome
hemangiomas, arterial anomalies, cardiac defects
(e.g., coarctation of the aorta), and eye
abnormalities

An infant with a large hemangioma on the upper Amblyopia
eyelid is at risk for
What is the best treatment for a hemangioma on Oral propranolol
the upper eyelid that obstructs the visual axis?
Annular plaque without scale not responding to Granuloma annulare
topical antifungals
An infant with orange to brown macules and Urticaria pigmentosa (cutaneous mastocytosis)
papules that become red and swollen when stroked
An infant with a 4-month history of seborrheic Langerhans cell histiocytosis
dermatitis-like rash on the scalp, behind the ears,
and in the diaper area not responsive to topical
antifungals or steroid cream
A 12-year-old boy with learning disabilities and Tuberous sclerosis
seizure disorder presents with persistent papules on
the face despite acne treatment. He is also found to
have hypopigmented skin lesions on the exam
A 10-month-old with light brown macules and Six
small patches on the body. How many café-au-lait
macules should raise concern for
neurofibromatosis?
What is the treatment for head lice? Permethrin 1% liquid; 2 treatments spaced
1 week apart
What is the treatment for scabies? Permethrin 5% cream; 2 treatments spaced
1 week apart
PSYCHOSOCIAL ISSUES AND CHILD ABUSE
Mohamed Zebda
Last-Minute Review—Psychosocial Issues and

Child Abuse Most Likely Answer
Factors that determine the understanding of death Chronologic age and levels of cognitive
and expression of grief development
What does exposure to high levels of parental Predictive of poor emotional adjustment by the
conflict lead to? child regardless of the parents’ marital status
What are the most helpful measures for children in Regular schedule with flexibility
cases of divorce? Consistency with structure and routine
Cooperative co-parenting
Consequences of divorce on a child’s emotional May affect his/her subsequent intimate
adjustment relationships
Consequences of adoption on children from A higher risk of medical and developmental
institutional or orphanage care problems than their counterparts who have
resided in foster care
Child is being placed in foster care; how soon Initial visit should take place within 72 h after
should this child be evaluated by a provider? placement in the foster care system
1126 O. I. Naga

TV watching is not recommended at what age? Children younger than 2 years of age
How long should children 2 years and older be 2 h/day or less for all children, including other
allowed to watch TV? forms of screen (solitary TV watching is highly
discouraged)
Increased aggressive behavior and acceptance of Excessive media time
violence, obscuring of the distinction between
fantasy and reality, trivialization of sexuality are
effects of
One of the most common causes of school refusal Separation anxiety disorder
in children
A set of clinical features in which unfounded Vulnerable child syndrome
parental anxiety about the health of a child results
in disturbances of the parent–child interaction
At what age should discussions start regarding Around 12 years of age
transition of care for adolescents and young adults
with chronic medical conditions?
A child tends to have asynchronous developmental Gifted child
patterns, very advanced in one domain area
compared to the rest
Maternal depression, substance use/abuse, and May indicate intimate partner violence
physical injuries
A frequent risk factor for child abuse Intimate partner violence
Consequences of children who are exposed to More likely to exhibit aggressive/violent
corporal punishment and intimate partner violence behaviors than other children
What is the most common form of child abuse? Neglect
What is the most common presentation in an Asymptomatic—just because there are no
abused child? physical signs does not mean that the child has
not been abused
What is the most common cause of head injury in a Child abuse
child less than 1 year of age?
A 3-week-old girl presents to ER with lethargy, Abusive head trauma (shaken baby syndrome)
poor sucking, and retinal hemorrhages; mother
stated the child rolled over and fell from the bed.
What are the consequences of child abuse during Physiologic and anatomic changes in the brain,
early development? increased risk of physical and behavioral
problems
Parents or guardians who failed to provide Medical neglect
adequate medical care for a child, e.g., refused to
administer medications for a serious medical
condition
Parents or guardian fail to provide basic needs Physical neglect
(nutrition, shelter, clothes) or who abandon the
child

Parents or guardian fail to enroll the child in school Educational neglect
or provide homeschooling, allow frequent
absenteeism, or ignore special education needs
Parents or guardian isolate the child, withhold Emotional neglect
emotional support, expose the child to
interpersonal violence or substance abuse, e.g.,
fight or engage in sex in front of the child
Parents or guardian leave the child alone or Supervision neglect
improperly supervised, fail to keep the child from
safety hazards, e.g., leaving strong chemicals open
and not safely secured in the house
Posterior rib fracture, bucket handle fracture, Child abuse
femur fracture in child less than 1 year old, distal
humeral physeal fracture, and humeral shaft
fracture in child less than 3 years old are high
suspicion of
Bucket handle fracture (also known as a classic High specificity for child abuse. It may occur
metaphyseal fracture or metaphyseal corner with shaking, vigorous pulling or twisting of an
fracture) in infants infant’s extremity
What is the next best step with any suspicion of Skeletal survey
child abuse in a child less than 2 years of age?
Difference between bucket handle fractures and Fracture of the distal radius (buckle fracture) is
buckle fractures common and is not associated with child abuse
A 7-month-old healthy infant with a few bruises on Must be evaluated for child abuse and reported
arms and legs to child protective services
A 7-year-old healthy child with multiple bruises on Reassurance
both tibial shins and elbows
Entire foot is burned, with a well-demarcated line Child abuse (possible forced immersion into hot
of injury around the leg and absence of splash water)
marks (stocking distribution)
Entire hand is burned, with a well-demarcated line Child abuse (possible forced immersion into hot
of injury around the forearm and absence of splash water)
marks (glove distribution)
What is the most common physical examination Normal examination
finding in a child with sexual abuse?
Physical contact between the victim and the Child sexual abuse
perpetrator, with or without oral, anal, or vaginal
penetration
Which gender is less likely to disclose sexual Boys
abuse and might be victimized more often than the
reported ratio
A 16-year-old adolescent presents to the ER due to SANE exam—should be done by a specialized
a sexual assault that occurred 1 day ago, what nurse. The cutoff for exam 72–120 h (within
should be done? 5 days)
1128 O. I. Naga

What is the SANE exam? Exam performed by a Sexual Assault Nurse
Examiner who examines the victim of sexual
assault and collects all forensic evidence
A healthy child with multiple recurrent ER visits; Caregiver-fabricated illness
the mother is a healthcare professional who
demands tests and imaging with each visit; before
discharge patient’s blood glucose is 40 mg/
dL. Further evaluation shows high serum insulin
level and absence of serum C-peptide level
ETHICS
Mohamed Zebda
Last-Minute Review—Ethics Most Likely Answer

The ethical principle of referring a child to an Beneficence (doing good for others or the best
expert in the field or providing the best treatment interest of the patient)
available, considering treatment efficacy and
potential to lessen disability
The ethical principle of not ordering a head CT Nonmaleficence (do no harm)
scan for a well-appearing child with trivial head
injury or referring a child with obstructive sleep
apnea secondary to enlarged tonsils and adenoids
to ENT (weighing the risks and benefits in each
case and avoiding possible complications)
The ethical principle of informing an adolescent Veracity (truthfulness or truth-telling)
about their diagnosis
The ethical principle of maintaining the Fidelity, e.g., maintaining confidentiality or
confidentiality of emancipated minor with STD faithfulness
The ethical principle of ideal distribution of risks Justice, e.g., clinical research trials in children
and benefits, and resolving potential conflict
The ethical principle of ensuring access to medical Justice
care with federally sponsored child health
insurance
The ethical principle of autonomy of thought, Autonomy
intention, and action when making decisions
regarding health care procedures or treatment
Newborn with ambiguous genitalia. What is the A multidisciplinary team should give parents as
best strategy in helping the parents consider the much information as possible about their child’s
gender in which to rear the child? diagnosis and prognosis

Family desires to continue invasive therapy for Physicians are not obligated to provide futile
child with irreversible and devastating neurological care
damage. The critical care physician and the
neurologist strongly believe that there will be
neither benefit nor quality of life for the child in
continuing life support
What is the best approach to the family in the Physicians must provide families with relevant
previous example? risks and benefits of available options and to
provide specific recommendations
Declaration of brain death requires Two independent examinations, including a
physical examination and apnea testing
Following the agreement of parents or guardian for 7 years and older (unless cognitively impaired)
a child to participate in clinical research, at what
age is consent of the child also required?
A physician is receiving financial incentives for This practice is prohibited because of the
recruiting children to participate in a clinical drug potential element of undue influence and
trial coercion
What are the most critical criteria required to Consent of guardians, child ≥ 7 years, the best
conduct a clinical drug trial in children? interests of the child, minimizing harm, safety
committees, monitoring, meaningful and
measurable outcomes
How should the consent document for the clinical Easy to understand (sixth to eighth-grade
trial or research be written? reading level)
What is the age of a minor to give consent for Laws related to minor consent vary by state
screening of sexually transmitted infections,
consent for contraceptive services, and consent for
general medical care?
At what age are contraceptive pills (progestin-only 17 years of age and older
emergency contraceptive) available over the
counter (OTC) to adolescents in all states in the
USA?
What is a minor called if the minor is married, in Emancipated minor (has the right to provide
the military, a parent, self-supporting while not informed consent for medical care). The criteria
living with parents, or a high school graduate? vary by jurisdiction
A 4-year-old boy involved in a car accident Transfuse the child (informed consent is not
requires a lifesaving blood transfusion. His adult required to treat a child with a life-threatening
parents refuse based on religious reasons. What condition)
should be done?
A 19-year-old involved in a car accident requires a Respect the patient’s wishes and do not transfuse
lifesaving blood transfusion. Based on religious (patient is an adult)
reasons he is refusing the blood transfusion. What
should be done?
The process in which the risks and benefits along Informed consent—must be sought from the
with potential alternatives are discussed with the parents unless there is a life-threatening
parents before performing any procedure is known emergency and unable to contact them
as
1130 O. I. Naga

A 16-year-old teenager requests confidential STD Do not disclose the results and protect patient
testing and pregnancy test. The mother comes confidentiality
without her child to demand the results of the
pregnancy/STD testing. What should you do?
A 16-year-old teenager positive for gonorrhea is in Do not tell the boyfriend, report her diagnosis to
the office with her 17-year-old boyfriend, who is the CDC. Encourage her to inform him herself
waiting outside. She begs you not to tell him about
her diagnosis. What should you do?
In what situation is a breach in confidentiality Risk of harming self or others
allowed, and parents or guardian must be notified
about an adolescent’s medical condition?
The mother of a 15-year-old female is here to Disclose the results to the mother (guardian)
obtain lab results that were ordered for obesity.
The patient is unable to be present. What should
you do?
You are seeing a 15-year-old female who says she A report should be filed with child protective
has had consensual sexual activity with her services—the child is a minor (age may vary by
boyfriend who is 21 years old. What should be state) and the boyfriend is an adult
done in this situation?
At what age is a minor considered developmentally The beginning of 12–13 years of age (mature
mature and able to understand the consequences of minor doctrine)
his or her medical decision, and thus should be
involved in making decisions about their medical
care?
Parents have asked the pediatrician not to reveal a Arrange a meeting with parents and the
diagnosis to their adolescent because of the adolescent to discuss the diagnosis and
psychological impact. What is the best approach? prognosis and provide psychological support if
needed
A 10-year-old girl recently diagnosed with a brain Discuss the diagnosis and treatment with parents
tumor; parents are asking you not to tell the child and the child (the child must know)
about her condition. What should be done in this
situation?
What are the ethical principles in the previous 2 Veracity (truthfulness or being honest) and
examples? fidelity (faithfulness)
A 15-year-old boy with terminal cancer has been Medical team meeting with the child and family
hospitalized for 3 months because of life- to elicit his preferences, inform him and his
threatening complications and recurrent relapses. family about end-of-life decisions, improve
He decides to discontinue his medical care, and the communication, and increase agreement among
family desires to continue treatment regardless of all involved parties regarding end-of-life care
outcome. What is the best approach to the end-of
life-care?
A family with a well-known adult-onset genetic No testing until the children reach adulthood
disorder (in the fifth to sixth decade) desires (after 18 years of age) when able to make an
genetic testing for their children to know their independent and informed decision
future risks

Parents are new to your practice and refuse Listen to parents and address all their concerns
vaccinations to their children about vaccines
Explain all risks and benefits of the vaccines in
question
Parents continue to reject the vaccination to their Continue their care. Discuss risks and benefits in
children each subsequent visit
If parents continue to refuse vaccinations for their No. Pediatrician should continue care unless a
child, is the pediatrician obligated to dismiss the strong sense of distrust develops that impacts a
child from his or her practice? child’s overall care
Parents brought their unimmunized 7-year-old boy Report the family to state welfare agency
who is bleeding from a raccoon bite. Parents refuse (medical neglect)
rabies vaccine
RESEARCH AND STATISTICS
Mohamed Zebda
Last-Minute Review—Research and Statistics Most Likely Answer

Study best suited to evaluate the risks and benefits Randomized control trial
of a new treatment, establishes a direct causal
relationship between treatment and outcomes
Study in which 2 groups are followed Cohort study (type of observational study)
prospectively over time to see which exposures/
risks cause disease and to provide information
about prognosis
Retrospective study in which people with a disease Case-control study (type of observational study)
are compared to those without the disease to
evaluate risk factors, useful for rare outcomes
Type of study used to compare a new diagnostic Cross-sectional study
test to the current gold standard diagnostic test in a
given population
Retrospective statistical analysis of several studies Meta-analysis
on the same topic
What is the best way to eliminate confounding Randomization of study subjects
variables?
Type of bias that occurs when an association Confounding bias
between an exposure and an outcome is distorted
by another variable
The percent of people with the disease in a given Prevalence
population being studied
The number of new cases of a given disease in a Incidence
specific period of time
The probability of correctly identifying those who Sensitivity = TP/(TP+FN)
truly have the disease SnOUT sensitivity → rules out disease when
they’re negative
1132 O. I. Naga
Last-Minute Review—Research and Statistics Most Likely Answer

The probability of correctly identifying those who Specificity = TN/(TN+FP)
truly do not have the disease SPIN specificity → rules in disease when they’re
positive
The probability of correctly identifying those who Positive predictive value = TP/(TP+FP)
truly have the disease among those whose tests are
positive
The probability of correctly identifying those not Negative predictive value = TN/(TN+FN)
having a disease among those whose tests are
negative
The hypothesis of no difference, i.e., daily Null hypothesis
exercising does not reduce the risk of heart disease
The hypothesis of difference, i.e., daily exercising Alternative hypothesis
does reduce the risk of heart disease
Rejecting the null hypothesis when in fact it is Type 1 error
true—a difference that was seen when one does
not exist
Failure to reject the null hypothesis when the null Type 2 error
hypothesis is false—a difference that was not seen
when one does exist
The probability that a study can detect a treatment Power of a study
effect
A range of values with a specified probability that Confidence interval
a given parameter falls in that range
What is the interpretation of a confidence interval There is no statistical significance
that includes 0 or 1
The total number needed to treat to prevent one The number needed to treat
bad outcome or adverse events NNT = 1/absolute risk reduction
The total number of patients receiving intervention The number needed to harm
for each patient that is harmed NNH = 1/attributable risk
ATIENT SAFETY AND QUALITY

P
IMPROVEMENT
Mohamed Zebda
Last-Minute Review—Patient Safety and Quality

Improvement Most Likely Answer
Wrong plan to achieve a desired aim Medical error
An error reaches the patient but does not result in Non-intercepted near miss error
harm
Recognized and corrected errors before it reaches Intercepted near miss error
the patient
An unexpected occurrence of death or serious Sentinel event
physical or psychological injuries
Last-Minute Review—Patient Safety and Quality

Improvement Most Likely Answer
A 4-year-old child with leukemia who requires a Sentinel event
transfusion receives the wrong type of blood,
resulting in a serious transfusion reaction
When a sentinel event has been identified, an Root cause analysis
investigation is undertaken immediately to
determine the root causes that have led to the
event. An action plan is then developed and
implemented to monitor the system in order to
minimize the risk that such an event will recur in
the future
A patient who is allergic to penicillin was Preventable medical error
prescribed amoxicillin and developed a skin rash
after drug administration
A patient with no history of allergic reaction to Non-preventable medical error
penicillin developed a severe allergic reaction to
amoxicillin
Suspected child physical or sexual abuse is an Mandatory reporting
example of
Serious reportable hospital events that should not Never events
have occurred, resulting in death or significant
disability
Mistakenly, a surgery was performed on the Surgical never event
healthy left knee instead of the right knee with torn
ligaments
Frequent nonclinically relevant alarm alerts result Alarm fatigue (adjust alarm thresholds to reduce
in desensitization to the alarms, and caregiver may nonclinically relevant noises); patients’
miss some signals that should necessitate an variability should be considered
intervention
What are some ways to prevent dosing and Avoid trailing zeros such as 20.0 mg
medication errors? Use leading zeros such as 0.1 mg
Avoid abbreviations such as BID
Write out unit
What are some ways to prevent medication Syringes are the preferred dosing device,
administration errors? measuring cups and spoons calibrated and
marked in milliliters are acceptable alternatives
Child in your clinic received the wrong Provide apology to parents
immunization; what should be done in this The error should be disclosed to the parents in a
situation? clear manner, and the steps that need to be taken
to prevent further errors should be discussed
What are the components of a successful quality Plan—what will be changed/what intervention
improvement project? Do—try the change on a small scale
Study—analyze results of the change/
intervention
Act—implement changes on a larger scale
1134 O. I. Naga
PHARMACOLOGY AND PAIN MANAGEMENT
Mohamed Zebda
Last-Minute Review—Pharmacology and Pain

Management Most Likely Answer
The time it takes the plasma concentration of a Half-life (t½)
drug to decrease by half
The lowest concentration reached by a drug before Trough levels
the next dose is administered
The highest concentration reached by a drug after Peak level
the dose is administered
Child is taking griseofulvin for tinea capitis. What To be taken with whole milk or fatty meal
is the best recommendation to maximize
absorption?
Child is taking oral penicillin for streptococcal Non-IgE-mediated
infection developed non-pruritic rash, nausea, and
vomiting. What is the type of this reaction?
Child is taking oral penicillin for streptococcal IgE mediated “anaphylaxis” to penicillin
infection developed pruritic rash, swollen lips and
difficulty breathing. What is the type of this
reaction?
What is the most common side effects of drugs in Nausea
general?
Anxiolysis with the maintenance of consciousness Minimal sedation
Controlled depressed consciousness, airway Moderate sedation (conscious sedation)
reflexes, and airway patency are maintained; the
patient responds appropriately to age-appropriate
commands and touch
Controlled depressed consciousness, airway Deep sedation
reflexes and airway patency may not be
maintained, ventilatory function may be impaired,
patient not easily aroused but responds
purposefully following repeated or painful
stimulation
Loss of consciousness occurs; impaired airway General anesthesia
reflexes, airway patency, and ventilatory function;
not arousable; not responsive to painful stimulation
In order to decrease the requirements of morphine Give an appropriate dose of acetaminophen (oral
post-operatively in neonates, infants, and children, or rectal) for mild to moderate pain even after
what is the best recommendation? major surgeries
Complication of gentamicin therapy, especially in Ototoxicity
newborns?
Which complication is associated with Pyloric stenosis
erythromycin in children less than 1 month?
Complication of tetracyclines in children less than Teeth staining
8 years old
Last-Minute Review—Pharmacology and Pain

Management Most Likely Answer
Mother is asking if she can give her 5-month-old Not recommended; increases the risk of
benzocaine gel for teething methemoglobinemia
What are the common side effects of ADHD Weight loss, difficulty sleeping, palpitations
medications?
In young children with aspirin use, and concurrent Reye syndrome
viral infection such as varicella, may cause
Index
A pain, 757, 758

Abdominal masses, 50 surgical abdominal emergencies, 201–204
Abdominal migraine, 759, 760 Acute Addison disease, 450
Abdominal pain Acute appendicitis, 761, 762, 966
acalculous cholecystitis, 765 Acute bronchiolitis, 707, 708
acute abdominal pain, 757 Acute cerebellar ataxia, 575
acute appendicitis, 761, 762 Acute chest syndrome
acute pancreatitis, 763 clinical presentation, 362
cholangitis, 765 etiology, 362
cholecystitis, 764–765 treatment, 362
choledocholithiasis, 765 Acute hematogenous osteomyelitis, 469, 470
cholelithiasis, 764 Acute intermittent porphyria (AIP), 161–162
chronic, recurrent pain, 760 Acute interstitial nephritis (AIN), 820, 821
cyclic vomiting, 759, 760 Acute kidney injury (AKI), 819–820
functional abdominal pain, 757–759 Acute laryngitis, 638
intussusception, 763 Acute left MCA territory infarction, 1007
malrotation, 762 Acute leukemia, 375
recurrent pancreatitis, 763–764 Acute life-threatening event (ALTE), 725, 726
referred pain, 760, 761 Acute lymphoblastic leukemia (ALL)
volvulus, 762, 763 ataxia telangiectasia, 376
Abdominal trauma, 210 Bloom syndrome, 376
Abdominal wall defects, 50–52 clinical presentation, 375
Abnormal alpha-fetoprotein (AFP), 37 diagnostic evaluation, 375, 376
ABO incompatibility epidemiology, 375
classification markers, 348 Fanconi anemia, 377
clinical approach to child with anemia, 348 peripheral blood abnormalities, 375
clinical presentation, 347 treatment, 375
diagnosis, 348 Trisomy 21, 376
prevalence, 347 Acute mastoiditis, 616
treatment, 348 Acute myeloid leukemia (AML)
Acalculous cholecystitis, 765 associated syndromes/risk factors, 377
Acanthosis nigricans, 463, 884 clinical presentation, 377
Accommodative esotropia, 604 diagnostic evaluation, 377
Acetaminophen ingestion, 223–225 epidemiology, 377
Achondroplasia, 131–132, 994 peripheral blood abnormalities, 377
ACID-BASE treatment, 377
metabolic acidosis, 836–837 Acute osteomyelitis, 988
metabolic alkalosis, 837, 838 Acute otitis media (AOM)
regulation, 836 antimicrobial therapy, 613
Acne vulgaris, 860–862 clinical presentation, 613
Acquired bleeding disorders common pathogens, 613
disseminated intravascular coagulopathy, 373 complications, 613
hemorrhagic disease of newborn, 373 diagnosis, 613
vitamin K deficiency, 373 management, 613
Acquired nystagmus, 606 myringotomy and tympanostomy tubes, 615
Acrocyanosis, 43 risk factors, 613
Acrodermatitis enteropathica, 860 signs of, 613
Acromegaly, 428 Acute pancreatitis, 763
Acromioclavicular (AC) dislocation, 515–516 Acute pericarditis, 679, 680
Active tuberculosis, 958 Acute postinfectious glomerulonephritis, 808, 809
Acute abdomen Acute respiratory distress syndrome (ARDS), 960
age-dependent presentation, 201 Acute rheumatic fever (ARF), 675
initial resuscitation, 202 Acute rhinosinusitis, 624–625
non-surgical causes, 202–204 Acute right testicular torsion, 983

O. I. Naga (ed.), Pediatric Board Study Guide, https://doi.org/10.1007/978-3-030-21267-4
1138 Index
Acute stress disorder, 182 Alternative hypothesis, 918

Acute tubular necrosis (ATN), 821 Alkaptonuria, 149
Acyanotic shunt lesions, 661 Allergic rhinitis (AR)
Acyclovir, 935 allergens, 391, 392
Adamantanes, 279 clinical presentation, 392
Addison disease, 450 comorbidities, 391
Adenotonsillectomy, 629 diagnosis, 393
Adenovirus, 276 intermittent disease, 392
clinical presentation, 277, 278 persistent disease, 392
incubation period, 277 treatment, 393, 394
laboratory test, 278 Allergy
mode of transmission, 277 adverse drug reactions
respiratory viruses, 278 cross-reactivity, 400
treatment, 278 desensitization, 400
Adenylate deaminase deficiency, 155 immune response, 400
Adjustment disorders, 183 specific drug reaction, 400
Adolescence, development and physiological changes timing of reaction, 400
boys, puberty sequence anaphylaxis (see Anaphylaxis)
peak height velocity, 81 AR (see Allergic rhinitis (AR))
penile growth, 81 causes, 391
pubarche, 81 food (see Food allergy)
testicular volume increase, 81 hypersensitivity types, 391, 392
emancipation and health care decisions, 83 and immunology, 1066–1070
girls, puberty sequence insects
menarche, 81 anaphylactic reactions, 401
peak height velocity, 81 diagnosis, 402
pubarche, 81 large local reactions, 401
thelarche, 81 systemic cutaneous reactions, 401
routine health visit treatment, 402
anticipatory guidance, 84, 85 mastocytosis (see Mastocytosis)
immunization, 84 serum sickness
interview, 83 causes, 401
laboratory, 84 clinical presentation, 401
physical examination, 84 treatment, 401
sexuality, 83 skin testing
skeletal growth, 82 ELISA, 403
tanner staging, 82 first-generation antihistamine, 403
cognitive development, 82 immunotherapy, 403, 404
common problems, 82 indications, 402
family influence, 83 medications, 402, 403
hematological changes, 82 method of testing, 403
hospitalizations, 82 second-generation antihistamine, 403
identity development, 82 specific triggers avoidance, 403
management of poor self-image, 82 steroid, 403
psychological separation, 83 urticaria (see Urticaria)
risks and conditions, 82 Alopecia areata, 880–881
Adolescent idiopathic scoliosis (AIS), 475–476 5-alpha-reductase deficiency, 455
Adolescent medicine, 1027–1032 Alpha thalassemia, 351
Adolescents to young adulthood, Alport syndrome, 619, 810
vulnerable populations, 893 Altered mental status (AMS)
Adrenal disorders coma, 219
Addison disease, 450 consciousness, 219
adrenal insufficiency, 449, 450 CSF shunt malfunction, 221
Cushing syndrome, 448, 449 definition, 219
hyperaldosteronism, 449 delirium (agitation), 219
PCOS, 451, 452 etiology of, 219, 220
pheochromocytoma, 451 Glasgow Coma Scale score, 220
Adrenal hemorrhage, 981 infection, 221
Adrenal insufficiency, 450 lethargy, 219
Aedes mosquitoes, 288 management, 221
Aggression metabolic anomalies, 221
associated conditions, 179 neoplasm, 221
childhood aggression, 178 obtunded, 219
clinical presentation, 178, 179 toxic ingestions, 221
etiology, 178 trauma, 221
management, 179 Alveolar rhabdomyosarcoma, 387
screening and rating scales, 179 Ambiguous genitalia, 52–53
Alagille syndrome, 124–125, 671, 792 Amblyopia, 605
Albinism, 876 Amenorrhea
Albright hereditary osteodystrophy (AHO), 437 causes, 91
Index 1139
clinical approach, 91, 92 Ancylostoma duodenale, 332

contraception, 95 Androgen insensitivity syndrome (AIS), 455
dysfunctional uterine bleeding, 93 Anemia
dysmenorrhea, 92 in newborn, 345, 346
gynecomastia, 94 in older children, 349
imperforate hymen, 93 prevalence, 345, 346
labial adhesions, 93 Aneurysmal bone cyst (ABC), 502, 503, 993
ovarian cyst, 94 Angelman syndrome, 126–127
ovarian torsion, 93 Angular deformities
PCOS, 92 blount disease (Tibia Vara), 485–486
primary amenorrhea, 91 genu valgum (knock-knee), 485
scrotal masses, 94 genu varum (bowleg), 484–485
secondary amenorrhea, 91 Anisocoria, 593
American Academy of Pediatrics (AAP), 1019 Ankle fractures, 499–501
Amino acid metabolism disorder, 150 Ankle sprain, 517
alkaptonuria, 149 Ankyloglossia/tongue-tie, 47, 631
glycine encephalopathy, 150 Anorexia nervosa, 88
homocystinuria, 149 complications, 89
non-classic phenylketonuria, 149 laboratory, 89
phenylketonuria, 148 management, 90
tyrosinemia type I, 150 subtypes, 89
tyrosinemia type II, 150–151 Anterior cruciate ligament (ACL) injury, 482
191-amino acid (191-AA) single chain polypeptide, 422 Anterior fontanelle, 44
Aminoglycosides, 930 Anterior plagiocephaly, 130
Amniocentesis, 112 Anterior shoulder (glenohumeral) dislocation, 515
Amniotic band disruption sequence, 139–140 Anterior uveitis, 590
Amoxicillin-clavulanate, 931 Antibody deficiency syndromes
Ampicillin, 930–931 CVID (see Common variable immune deficiency (CVID))
Amplified musculoskeletal pain syndrome sIgAD (see Selective IgA deficiency (sIgAD))
(AMPS), 542, 543 THI (see Transient hypogammaglobulinemia
Anaerobes of infancy (THI))
Clostridium botulinum, 302 X-linked agammaglobulinemia
Clostridium difficile BTK defect, 408
clinical presentation, 304 clinical presentation, 408
diagnosis, 304 diagnosis, 408
prevention, 304 treatment, 408
risk factor, 303 Anticholinergics ingestion, 226
treatment, 304 Antidotes, 223
Clostridium perfringens, 302, 303 Antiemetics, 941
Clostridium tetani Anti-epileptic drugs (AED), 558
common sources, 303 Antifreeze, 229
generalized tetanus, 303 Anti-glomerular basement disease, 812, 813
neonatal tetanus, 303 Antihypertensive medications, 939–940
prevention, 303 Anti-IL-1 agents, 531
treatment, 303 Anti-IL-6 agent, 531
foodborne botulism, 302 Anti-Müllerian hormone (AMH), 452
Anagen effluvium, 881 Antiparasitics, 936–937
Anaphylactic shock, 257 Antiphospholipid antibody syndrome (APS), 534
Anaphylaxis Anti-pseudomonal penicillins, 931
biphasic presentation, 205 Antisocial behaviors and delinquency
causes associated conditions, 178
exercise, 398 clinical presentation, 177
food, 397 etiology, 177
immunotherapy, 398 FISTS, 178
latex, 398 management, 178
medications, 397 prevention, 178
radiographic contrast, 397 rating scales, 178
stinging insects, 398 risk factors, 177
vaccination, 398 Anti-TNF alpha agents, 531
clinical presentation, 398 Anti-ulcers, 940–941
definition, 204 Antivirals
diagnosis, 205 acyclovir, 935
differential diagnosis, 205, 398 foscarnet, 935
home care, 206 ganciclovir (IV), 935
pathophysiology, 204 nonnucleoside reverse transcriptase inhibitors, 936
patient disposition, 206 nucleoside reverse transcriptase inhibitors, 935–936
signs and symptoms, 397 other agents, 935
symptoms, 205 protease inhibitors, 936
treatment, 205, 206, 398, 399 valacyclovir, 935
ANCA-associated vasculitis (AAV), 543 valganciclovir, 935
1140 Index
Anxiety disorder laboratory evaluation, 534, 535

associated conditions, 181 management, 535
developmental fears, 180 musculoskeletal manifestations, 533
generalized anxiety disorders, 180 neuropsychiatric manifestation, 533
genetics, 180 pulmonary manifestations, 534
management, 181 renal manifestations, 533
obsessive compulsive disorders, 181 localized scleroderma, 536, 537
panic disorder, 180 MCTD, 537
parenting styles, 180 NLE, 535
prognosis, 181 PSRA, 531
screening and rating scales, 181 reactive arthritis, 532
selective mutism, 180 Sjögren syndrome, 537
separation anxiety disorder, 180 systemic scleroderma, 536
social phobia, 180 Arthrogryposis, 466
Aortic stenosis, 671, 672 Ascaris lumbricoides
Apert syndrome, 130 clinical presentation, 332
Apgar Score, 43 diagnosis, 332
Aphthous ulcers, 630 mode of transmission, 332
Aplasia cutis congenita, 43 treatment, 332
Aplastic anemia, 370 Aseptic meningitis, 273, 338
Aplastic crisis Aspergillus species
clinical presentation, 363 causes, 327
etiology, 363 clinical presentation, 327
laboratory test, 363 diagnosis, 327
treatment, 363 mode of transmission, 327
Apnea, 699, 700 treatment, 327
Apophyseal avulsion fracture, 996 Asphyxial arrest, 251
Arbovirus Asthma
dengue fever acute asthma exacerbations, 714
clinical presentation, 289 assessment, 710, 711
epidemiology, 288 beta-2 agonists, 712, 713
laboratory test, 289 classification, 711
treatment, 289 differential diagnosis for, 710
West Nile virus EIA, 711, 712
clinical presentation, 288 inhaled corticosteroids, 713
diagnosis, 288 initial controller therapy, 713
epidemiology, 288 leukotriene receptor antagonists, 714
treatment, 288 management of, 712
Arcanobacterium haemolyticum, 301, 302 pathophysiology, 710
Arnold–Chiari malformation type I, 564 symptoms and natural course, 709, 710
Arnold–Chiari malformation type II, 564, 565 Asthma predictive index, 709
Arterial blood gases, 693 Astrocytoma, 383
Arteriovenous malformations (AVMS), 568, 870 Ataxia, 575
Arthritis Ataxia telangiectasia, 376, 575, 576
associated with rheumatic fever, 469 clinical presentation, 413
differential diagnosis, 526 diagnosis, 413
DIL, 536 risk of malignancy, 413
IBD, 532 treatment, 413
JIA Atlantoaxial instability, 570, 571
complications of, 530 Atlantoaxial subluxation, 472
definitions, 525 Atopic (seasonal) allergic conjunctivitis, 589–590
ERA, 527 Atopic dermatitis, 857–859
imaging, 530 Atrial fibrillation (AF), 647, 653, 654
laboratory abnormalities, 529, 530 Atrial septal defect (ASD), 662, 663
MAS, 529 Atrioventricular block (AVB), 658
oligoarticular, 526, 527 Attention-deficit/hyperactivity disorders (ADHD)
polyarticular, 527 administration of medications to children, 176
psoriatic, 528 associated conditions, 172
systemic-onset, 528 diagnosis, 172
treatment of, 530, 531 differential diagnoses, 172, 173
uveitis, 529 management, 173–176
jSLE risk factors, 172
APS, 534 screening and rating scales, 172
cardiac manifestations, 534 Auditory brainstem response (ABR), 620
clinical presentation, 532 Autism screening, 25
cutaneous manifestations, 532, 533 Autism spectrum disorders
endocrine manifestations, 534 diagnostic criteria, 168
gastrointestinal manifestations, 534 differential diagnosis, 168
general manifestations, 532 management, 169
hematologic involvement, 534 prognosis, 169
Index 1141
screening and testing, 168 clinical presentation, 313

Autoimmune hemolytic anemia (AIHA) diagnosis, 313
cold AIHA, 367 Klebsiella, 314
etiology, 366, 367 source, 313
warm AIHA surgical treatment, 314
laboratory test, 367 Bartter syndrome, 815
treatment, 367 Basilar skull fracture, 207
Autoimmune hepatitis (AIH), 796 Bat bites, 212
Autoimmune thyroiditis, 430, 431 Becker muscular dystrophy, 572
Autoinflammatory diseases Beckwith–Wiedemann syndrome (BWS), 136–137
CRMO, 540 Bedbugs, 866
FMF, 539, 540 Bedtime refusal/frequent awakening, 190–191
periodic fever syndromes, 539 Behavioral healthcare
sarcoidosis, 540, 541 adherence to medical regimens, 85
Automated external defibrillator (AED), 264 developmentally-appropriate psychosocial history, 85
Autosomal aneuploidies, chromosome disorders risk taking behaviors, 85
down syndrome, 113–116 stress, 85
trisomy 13/Patau syndrome, 116–118 violence, 85
trisomy 18/Edwards syndrome, 116 Behavioral observation audiometry (BOA), 620
Autosomal dominant (AD) inheritance Behçet disease, 547, 548
autosomal dominant inheritance, 104 Bell’s palsy, 574
examples, 105 Benign epilepsy with centrotemporal spikes
genetic transmission, 104 (BECTS), 553, 554
Autosomal dominant polycystic kidney disease (ADPKD), 818 Benign familial macrocephaly, 2
Autosomal recessive (AD) inheritance Benign familial neutropenia, 368
examples, 106 Benign joint hypermobility syndrome (BJHS), 542
genetic transmission, 105 Benign paroxysmal positional vertigo (BPPV), 617
new mutation, 106 Benign sleep myoclonus of infancy, 191
uniparental disomy, 105 Berger disease, 809, 810
Autosomal recessive polycystic kidney disease (ARPKD), 817, 980 Bernard Soulier syndrome, 373
AV nodal tachycardia (AVNRT), 654 Beta blockers ingestion, 226
Avian influenza H5N1 Beta lactam antibiotics, 930
clinical presentation, 279 Beta-2 agonists, 713
epidemiology, 279 Beta-Thalassemia
mode of transmission, 279 beta-thalassemia intermedia, 352
prevention, 279 beta-thalassemia major, 352, 353
Azithromycin, 302, 305–307, 309–313, 315–317, 325 beta-thalassemia minor, 352
clinical manifestations, 351
Bezoars, 769
B Bias
Bacillus anthracis, 301 confounding bias, 913
Bacillus Calmette-Guérin (BCG) vaccine, 323 definition, 913
Bacillus cereus, 301 Hawthorne effect, 913
Back disorders procedure bias, 913
adolescent idiopathic scoliosis, 475–476 pygmalion effect, 913
back pain, 472–473 recall, 913
Scheuermann kyphosis, 476, 477 reduction, 913
scoliosis, 474–475 selection, 913
spondylolisthesis, 474 Bifid uvula, 630–631
spondylolysis, 473–474 Bifidobacterium sp., 268
Back pain, 472–473 Bilateral cervical and brachial plexus plexiform
Bacterial conjunctivitis, 587 neurofibromas, 1000
causes, 586 Biliary atresia, 790–791, 972
clinical presentation, 587 Bilirubin-induced neurologic dysfunction (BIND), 60
management, 587 Biophysical profile test, 37
Bacterial infections Biotin, 736
cellulitis, 875 Biotinidase deficiency, 147
impetigo, 874–875 Bipolar disorder
intertrigo, 875–876 associated condition, 186
necrotizing fasciitis, 876 cyclothymic disorders, 186
staphylococcal scalded skin syndrome, 875 diagnostic criteria, 186
Bacterial meningitis, 309 early onset bipolar disorder, 186
Bacterial overgrowth syndrome, 782, 783 lifetime prevalence, 186
Bacterial tracheitis, 703, 704 management of, 186
Balanoposthitis, 847 prevention, 187
Baloxavir, 279 prognosis, 187
Bannayan-Riley-Ruvalcaba syndrome (BRRS), 789 screening and rating scales, 186
Bartonella henselae type I, 186
Citrobacter, 314 type II, 186
1142 Index
Birth defect Klumpke palsy, 48

amniotic band disruption sequence, 139–140 management, 49
Goldenhar syndrome/hemifacial microsomia, 138 Brachycephaly, 130
Pierre Robin sequence, 139 Bradycardia, 50
Poland sequence, 138–139 Brain abscess
VACTERL association, 140 antimicrobial therapy, 341
Black widow spider bite, 214 causes, 340
Blacklegged tick (Ixodes scapularis), 319 cerebellar abscesses, 340
Bladder Exstrophy, 846 clinical presentation, 340
Blastomyces, 328 frontal lobe abscesses, 340
Blood gas analysis, 693 laboratory diagnosis, 340
Blood pressure screening, 24 neuroimaging, 340
Bloom syndrome, 376 prognosis, 341
Blount Disease (Tibia Vara), 485–486 surgical intervention, 341
Blue sclera, 46 Brain death, 252, 253
Body fluid composition, 825 Brain malformations
Body odors, 164–165 Arnold–Chiari malformation type I, 564
Bohn nodules, 47 Arnold–Chiari malformation type II, 564, 565
Bone-anchored hearing aid, 622 corpus callosum, agenesis of, 565
Bone and joint infection/inflammation Dandy-Walker malformation, 565, 566
acute hematogenous osteomyelitis, 469, 470 lissencephaly, 565
diskitis, 470 polymicrogyria, 565
septic arthritis, 468–469 Brain tumors
transient synovitis, 468 associated syndrome, 384
vertebral body osteomyelitis, 470 astrocytoma, 383
Bone and mineral disorders clinical presentation, 383
albright hereditary osteodystrophy, 437 craniopharyngioma, 384
familial hypocalciuric hypercalcemia, 437 ependymoma, 384
hyperparathyroidism, 437, 438 hepatoblastoma
hypocalcemia (see Hypocalcemia) associated syndromes/risk factors, 385
hypoparathyroidism (see Hypoparathyroidism) clinical presentation, 385
pseudohypoparathyroidism, 436, 437 diagnosis, 385
Bone marrow biopsy, 376 incidence, 383, 384
Bone marrow infiltration, 369 treatment, 385
Bone tumors/tumors-like conditions medulloblastoma, 383, 384
aneurysmal bone cyst, 502, 503 pathologic diagnosis, 383
Ewing sarcoma, 504, 505 pineoblastoma, 384
osteochondroma, 503 Branchial cleft cyst, 637–638
osteoid osteoma, 503 Branchio-oto-renal syndrome, 619
osteosarcoma, 504 Breast milk, 268
unicameral cyst, 502 and formula, 744
Bordetella pertussis, 268 Breastfeeding, 269
catarrhal phase, 311 colostrum, 741, 742
convalescent phase, 311 mature breast milk, 742–744
diagnosis, 312 transition milk, 742
immunization, 312 Brief resolved unexplained event (BRUE), 725, 726
incubation period, 311 Bronchiectasis, 716, 717
paroxysmal phase, 311 Bronchogenic cyst, 704
pertussis complications, 311 Bronchopulmonary dysplasia (BPD), 708, 709, 836
prophylaxis, 312 Brown recluse spider bite, 214–215
thoracic pressure-related complications, 312 Brown-Vialetto-Van Laere syndrome, 737
treatment, 312 Brucellosis
Borrelia burgdorferi causes, 312
early disseminated disease stage II, 320 risks, 312
early localized disease stage I, 320 treatment, 313
incubation period, 320 Brugada syndrome, 686
late disseminated disease stage III, 320 Bruises, 896
treatment, 320 Bruton tyrosine kinase (BTK), 408
Botulism, 571 Bruxism, 183
Botulism immune globulin (BIG), 302, 571 Buccal infections, 310
Bowel obstruction, 248 Bulging fontanelle, 44
Bowel perforation with pneumoperitoneum, 963 Bullous impetigo, 297
Brachial plexus injuries (BPI) Bullying, 179, 180
associated injuries, 48 Burkitt lymphoma, 380, 381
classification, 48 Burns, 270, 754, 896
clinical presentation, 48 deep partial thickness burn, 215
diagnosis, 48 electrical burns, 216
Duchenne-Erb palsy, 48 extensive burns treatment, 217
Index 1143
full thickness burn, 215 VF, 657

inhalation injury, 216 VT, 657
Palmar method, 216 WPW syndrome, 655
partial thickness burn, 215 Cardiac glycosides ingestion, 227
Rule of Nines, 216 Cardiac tamponade, 680, 681
superficial burn, 215 Cardiogenic shock, 255
supportive home therapy, 216, 217 Cardiology, 1099–1104
Button battery ingestion, 974 Cardiopulmonary resuscitation (CPR)
AED, 264
chest compression depth, 263, 264
C chest compression rate, 263
Café-au-Lait Macules (CALM), 878 chest compression techniques, 264
Calcaneovalgus foot, 489–490 chest compression to breath ratio, 264
Calcium, 732 Cardiothoracic radiology
Campylobacter species active tuberculosis, 958
clinical presentation, 304 acute respiratory distress syndrome, 960
diagnosis, 305 congenital diaphragmatic hernia, 949
epidemiology, 304 congenital lobar emphysema, 951
treatment, 305 congenital pulmonary airway malformation, type II, 950
Candida albicans, 325 croup (laryngotracheobronchitis), 954
Candida species cystic fibrosis, 960
candidal diaper dermatitis Ebstein’s anomaly, 953
clinical presentation, 326 foreign body aspiration, 955
treatment, 326 long gap esophageal atresia with tracheoesophageal fistula, 952
etiology, 325 lymphoma, 961
neonates, 327 meconium aspiration syndrome, 949
oral thrush pulmonary interstitial emphysema, 948
clinical presentation, 326 pulmonary thromboembolism, 959
incidence, 325 round pneumonia, 956
infection sources, 326 surfactant deficiency disease, 947
recurrence, 326 tetralogy of Fallot, 953
risk of infection, 326 Cardiovascular disorders
treatment, 326 arrhythmias
vulvovaginitis AF, 653, 654
clinical presentation, 327 atrial rates, 653
risk factors, 326 AVB, 658
treatment, 327 ECGs, 652
Candidal diaper dermatitis, 326 history for, 646
Capillary blood gases (CBG), 693 LQTS, 656, 657
Capillary malformations, 869, 870 prolonged QT interval, 656
Caput succedaneum, 45 PVC, 656
Carbamazepine ingestion, 226–227 rhythm disturbance, 646
Carbapenems, 932 sinus arrhythmia, 652
Carbohydrate metabolism disorder, 156 SSS, 655
adenylate deaminase deficiency, 155 SVT, 654, 655
fructokinase deficiency, 155 VF, 657
fructose 1,6-diphosphatase deficiency, 155 VT, 657
galactokinase deficiency, 153 WPW syndrome, 655
galactosemia, 153 chest pain
glycogen storage diseases, 153 arrhythmias, 643
Pompe disease, 154 cardiac abnormalities, 643
Von Gierke disease, 154 clinical approach to, 644–645
Carbohydrates, 741 coronary artery diseases, 643
Carbon monoxide (CO) poisoning, 228 gastrointestinal causes of, 644
Carbuncle, 290 infections/autoimmune disorders, 643
Cardiac arrhythmias noncardiac causes of, 644
AF, 653, 654 noncardiac chest pain, 643
atrial rates, 653 psychogenic causes of, 644
AVB, 658 red flags, 643
ECGs, 652 respiratory causes of, 644
history for, 646 congenital heart defects, 661, 662
LQTS, 656, 657 dilated cardiomyopathy, 684
PACs, 652, 653 dyslipidemia, 686, 687
prolonged QT interval, 656 fetal cardiac output, 658
PVC, 656 genetics, 674, 675
rhythm disturbance, 646 HCM, 685
sinus arrhythmia, 652 heart failure
SSS, 655 causes, 682, 683
SVT, 654, 655 clinical presentation, 683
1144 Index
Cardiovascular disorders (cont.) diagnosis, 336, 337

diagnostic evaluation, 683 epidemiology, 336
management, 683, 684 initial evaluation, 336
infection/vasculitis treatment, 337
acute pericarditis, 679, 680 meningitis (see Meningitis)
ARF, 675 Cephalexin, 290, 298
cardiac tamponade, 680, 681 Cephalohematoma, 45
IE, 678, 679 Cephalosporins (penicillinase-resistant), 931–932
KD, 675–678 Cerebral edema
myocarditis, 681, 682 asphyxial arrest, 251
left-to-right shunts causes, 233
ASD, 662, 663 cytotoxic edema, 251
atrioventricular canal defects, 664, 665 initial resuscitation, 233
PDA, 665, 666 interstitial edema, 252
VSD, 663, 664 osmotic cerebral edema, 252
murmur, 660, 661 pathophysiology, 233
obstructive lesions risk factors, 233
aortic stenosis, 671, 672 signs, 233
coarctation of aorta, 673, 674 symptoms, 252
HLHS, 674 treatment, 233
PPS, 671 vasogenic edema, 251
pulmonary valve stenosis, 670, 671 Cerebral palsy, 510, 578, 579
restrictive cardiomyopathy, 684, 685 Cerebral salt wasting, 427, 428
right-to-left shunt lesions Cerebral venous thrombosis, 569
Ebstein anomaly, 668, 669 Cerebrospinal fluid analysis, 339
TAPVR, 669, 670 Cervical intraepithelial neoplasia (CIN), 289
tetralogy of fallot, 666, 667 Cervical lymphadenitis, 634–635
transposition of great arteries, 667, 668 Cervical spine injury, 209–210
tricuspid atresia, 667 Cestodes (platyhelminthes), 333
truncus arteriosus, 669 Chalazion, 591–592
sudden cardiac death, 686 Chediak–Higashi syndrome, 369
superior vena cava syndrome, 686 CHS1/LYST gene, 407
syncope, 645 clinical presentation, 407
Caregiver-fabricated illness, 900 diagnosis, 407
Carpenter syndrome, 130 risk of malignancy, 407
Cartilage hair hypoplasia, 369 treatment, 407
Castleman’s disease, 276, 636 Chemical conjunctivitis, 589
Cat bites, 212 Chemoprophylaxis, 269, 340
Cat scratch disease, 313–314, 635 Chest
Cataracts, 594, 595 breast hypertrophy and galactorrhea, 49
Caustic esophageal injuries, 768 clavicle fracture, 49
Caustic ingestion, 230 crepitation, 49
Cavus foot, 490 pain, 508
CD40 ligand (CD40L), 414 pectus excavatum, 49
Cefotaxime, 295 supernumerary nipple, 49
Ceftriaxone plus vancomycin, 295 Turner syndrome, 49
Celiac disease, 779, 780 Chiari malformation type I and type II, 564
Cellular immunity Chickenpox, 274, 275
CMC Child abuse
clinical presentation, 410 clinical background, 895
diagnosis, 410 clinical features, 897
feature, 410 clinical presentation, 896, 897
treatment, 410 diagnosis, 897
DiGeorge syndrome management, 897
CATCH 22, 409 report, 897
clinical presentation, 410 risk factors, 895
diagnosis, 410 Child-care centers, 267
prognosis, 410 Childhood absence epilepsy, 552, 553
treatment, 410 Childhood schizophrenia
types, 410 clinical presentation, 188
HIES (see Hyper-IgE syndrome (HIES)) differential diagnosis, 188
XLP syndrome (see X-linked lymphoproliferative (XLP) syndrome) management, 188
Cellulitis, 875 prognosis, 188
Central line-associated bloodstream infections (CLABSI), 270, 327 risk factors, 188
Central nervous system (CNS) infections screening, 188
brain abscess (see Brain abscess) Child neglect, 898
encephalitis Chlamydia pneumoniae, 308, 395
causes, 336 clinical presentation, 305
clinical presentation, 336 diagnosis, 305
definition, 336 epidemiology, 305
Index 1145
treatment, 305 Cleft lip and palate, 632–633

Chlamydia trachomatis, 97 Clindamycin, 291, 293–296, 298–300, 303, 304, 311, 331, 932
conjunctivitis due to Clonidine ingestion, 227
clinical presentation, 305 Clonorchis sinensis, 333
epidemiology, 305 Clostridium botulinum
treatment, 305 causes, 302
pneumonia due to clinical presentation, 302
diagnosis, 306 infant botulism, 302
etiology, 306 treatment, 302
treatment, 306 Clostridium difficile, 268
Chlamydophila psittaci, 305 clinical presentation, 304
Chloride (Cl), 732, 835 diagnosis, 304
Choanal atresia, 46, 623, 695 prevention, 304
Cholangitis, 765 risk factor, 303
Cholecystitis, 764–765 treatment, 304
Choledocholithiasis, 765 Clostridium perfringens, 302, 303
Cholelithiasis, 764 Clostridium tetani
Cholesteatoma, 616 common sources, 303
Chorioamnionitis generalized tetanus, 303
clinical history, 41 neonatal tetanus, 303
clinical presentation, 41 prevention, 303
management, 41 treatment, 303
Chorionic villus sampling (CVS), 112, 113 Clover-leaf skull or Kleeblattschädel anomaly, 130
Chromium, 732 Clubfoot (talipes equinovarus), 489
Chronic abdominal pain, 760 Coagulation disorders
Chronic benign neutropenia, 368 acquired bleeding disorders
Chronic bilirubin encephalopathy, 61 disseminated intravascular coagulopathy, 373
Chronic diarrhea, 784–785 hemorrhagic disease of newborn, 373
Chronic granulomatous disease (CGD) vitamin K deficiency, 373
clinical presentation, 406 bleeding disorder, 373
diagnosis, 406 erythrocytosis, 374
treatment, 407 inherited bleeding disorders
Chronic hypoxia, 700 hemophilia A and B, 374
Chronic illness, 893, 894 Von Willebrand disease, 374
Chronic keratoconjunctivitis, 306 polycythemia vera, 374, 375
Chronic liver disease, 753 Coalescent mastoiditis, 1011
Chronic lymphocytic leukemia (CLL), 378 Cobalamin, 354
Chronic mucocutaneous candidiasis (CMC) Coccidioidomycosis
feature, 410 mode of transmission, 328
treatment, 410 treatment, 328
Chronic myelogenous leukemia (CML), 378 Cochlear implants, 622
Chronic nonprogressive headache, 562 Cognitive and neurodevelopmental disorders
Chronic pain syndrome, 894 autism spectrum disorders
Chronic progressive headache, 562 diagnostic criteria, 168
Chronic recurrent multifocal osteomyelitis management, 169
(CRMO), 540 prognosis, 169
Chronic sinusitis, 625 screening and testing, 168
Chronic stridor intellectual disability
differential diagnosis causes, 167
choanal atresia, 695 classification, 167
laryngeal web, 696 clinical presentation, 167
laryngomalacia, 695 differential diagnosis, 168
laryngotracheoesophageal cleft, 697 management, 168
macroglossia, 697 prevalence, 167
SGS, 696 sensory over-responsivity, 169
subglottic hemangioma, 697 Cognitive behavioral therapy (CBT), 760
VCP, 695, 696 Cold agglutinin disease, 367
Chronic suppurative otitis media (CSOM), 615 Cold autoimmune hemolytic anemia, 367
Chronic urticaria Cold panniculitis, 631
causes, 395 Coloboma, 46, 593–594
diagnosis, 395 Colonic atresias, 774
differential diagnosis, 395 Colostrum and mature breast milk, 741, 742
treatment, 395 Combined antibody and cellular immunodeficiency
Circadian rhythm disorder, 191 ataxia-telangiectasia (see Ataxia-Telangiectasia)
Circumcision, 847, 848 SCID (see Severe combined immunodeficiency (SCID))
Citrobacter, 314 Wiskott–Aldrich syndrome (see Wiskott–Aldrich syndrome)
Clavicular fracture, 494 XHIM (see X-linked hyper-IgM syndrome (XHIM))
1146 Index
Common variable immune deficiency (CVID) Congenital muscular torticollis, 471

clinical presentation, 409 Congenital myotonic dystrophy, 572
definition, 409 Congenital nephrotic syndrome, 807
diagnosis, 409 Congenital neutropenia, 368
risk of malignancy, 409 Congenital pulmonary adenomatoid malformation, 705
treatment, 409 Congenital pulmonary airway malformation, 950
Communication disorder Congenital rubella syndrome, 287
language disorders, 169 Congenital sensory nystagmus, 606
phonological speech disorders, 169 Congenital syphilis, 320, 321
social communication disorder, 169–170 clinical presentation, 71
Compartment syndrome, 500 diagnosis, 71
Complement defect infection, 71
clinical presentation, 414 management, 71
diagnosis, 414 transmission rate, 71
initial defect, 414 treponema-specific tests, 71
terminal defect, 414 Congenital toxoplasmosis
treatment, 415 clinical presentation, 70
Complementary and alternative medicine (CAM), 910, 911 infection in first trimester, 70
Complete AV canal defect (CAVC), 662 infection in third trimester, 70
Concussion transmission risk, 70
definition, 234 treatment, 70
epidemiology, 235 Conjugated hyperbilirubinemia, 60
management, 235, 236 Connective tissue dysplasias
risk factors, 235 Ehlers–Danlos Syndrome (EDS), 134–135
signs and symptoms, 235 Marfan syndrome, 132–134
Conduct disorder osteogenesis imperfecta, 135–136
associated conditions, 177 Constitutional delay of growth and puberty (CDGP), 419
management, 177 Contact dermatitis, 859
prevention, 177 Contact lens-related problems, 606
prognosis, 177 Contraction stress test, 37
screening and rating scales, 177 Copper, 732, 733
Conductive hearing loss (CHL), 618 Corneal abrasion, 602
Condyloma acuminatum, 874 Corpus callosum, agenesis of, 565
Condylomata acuminata, 289 Corynebacterium diphtheriae, 300
Confidence interval, 919 Cough, 697, 698
Confounding bias, 913 Cowden syndrome (CS), 384, 789
Congenital adrenal hyperplasia (CAH) Craniofacial defects
causes, 453 craniosynostosis syndromes, 130–131
clinical presentation Treacher Collins syndrome, 129–130
in females, 453 Waardenburg syndrome, 129
in males, 454 Craniopharyngioma, 384, 425, 426, 1012
diagnosis, 454 Craniosynostosis syndromes, 3–4, 567
treatment, 454 abnormalities, 131
Congenital chloride, 785 causes, 130
Congenital diaphragmatic hernia (CDH), 949 health supervision and preventive care, 131
clinical presentation, 74 prevalence, 130
delivery room management, 74 types, 130
imaging studies, 74 Cri-du-chat syndrome, 122, 674
laboratory tests, 74 Crigler-Najjar syndrome, 791
management, 75 type 1, 60, 792
Congenital esotropia, 603 type 2, 60, 792
Congenital hearing loss, 618–619 Critical care, 1049–1052
Congenital heart block (CHB), 535 Critical congenital heart diseases screening, 39
Congenital heart defects, 661, 662 Crohn’s disease, 778, 976
Congenital hypopituitarism Croup (laryngotracheobronchitis), 954
clinical presentation, 424 Crouzon syndrome, 130
diagnosis, 424 Cryptorchidism, 52, 849, 850
Hall–Pallister syndrome, 423 Cryptosporidiosis
septo-optic dysplasia, 424 clinical presentation, 330
Congenital hypoplastic anemia, see Diamond–blackfan anemia treatment, 330
Congenital hypothyroidism Cryptosporidium, 269, 329
causes, 429 Culex mosquitoes, 288
clinical presentation, 429 Cultural issues in medical care, 891, 892
laboratory test, 429 Cushing syndrome, 448, 449
prognosis, 429 Cutaneous lupus erythematosus (CLE), 871–872
treatment, 429 Cutis marmorata, 44
Congenital lobar emphysema, 705, 706, 951 Cyanide ingestion, 228–229
Congenital long Qt syndrome (LQTS), 656, 657 Cyanosis, 700
Congenital melanocytic nevi (CMN), 879 Cyanotic lesions, 661–662
Index 1147
Cyclic neutropenia Dermal tumors

clinical presentation, 368 dermoid cyst, 880
laboratory test, 368 granuloma annulare, 879–880
treatment, 368 mastocytosis, 880
Cyclic vomiting, 759, 760 Dermatology, 1122–1125
Cyclothymic disorders, 186 acanthosis nigricans, 884
Cystic fibrosis (CF), 753, 780, 781, 960 acne, 860–862
clinical presentation, 717, 718 dermal tumors
complications, 718–720 dermoid cyst, 880
diagnosis, 719 granuloma annulare, 879–880
dysfunction/absence, 717 mastocytosis, 880
management, 719, 720 disorder of pigmentation
therapies for treatment, 720 albinism, 876
Cystic kidney diseases Café-au-Lait macules, 878
ADPKD, 818 dermal melanocytosis, 878
ARPKD, 817 nevus of Ito, 878
Laurence-Moon-Bardet-Biedl syndrome, 818, 819 nevus of Ota, 878
multicystic dysplastic kidney disease, 819 pityriasis alba, 876–877
NPH, 818 post inflammatory hypo/ hyper-pigmentation, 877
Cystinosis, 815, 816 vitiligo, 877
Cystosarcoma phyllode, 91 eczematous dermatitis
Cytochrome P450 (CYP) enzyme inhibitors, 928 acrodermatitis enteropathica, 860
Cytotoxic edema, 251 atopic dermatitis, 857–859
contact dermatitis, 859
keratosis pilaris, 859
D nickel dermatitis, 860
Dacryostenosis, 592 rhus dermatitis (Poison Ivy), 859
Dandy–Walker malformation, 565, 566 seborrheic dermatitis, 860
De Grouchy syndrome, 123 factitious disorders, 884
Death, 887, 888 fungal infections
Deep hematoma of thigh, 516–517 onychomycosis, 865
Deep partial thickness burn, 215 tinea capitis, 862, 863
Deformational plagiocephaly, 3, 4 tinea corporis, 863
Dehydration, 832, 833 tinea cruris, 864
Delayed dental eruption, 633 tinea pedis, 864
Delayed puberty, 446 tinea versicolor, 864
Delayed separation of umbilical cord, 51 genodermatoses
Delivery room care ectodermal dysplasia, 882–883
initial management, 38 epidermolysis bullosa, 881–882
resuscitation ichthyosis vulgaris, 883
indications, 38 incontinentia pigmenti, 882
newborn resuscitation, 38 hair disorders
process steps, 38 alopecia areata, 880–881
withholding resuscitation, 38 anagen effluvium, 881
temperature control, 38 telogen effluvium, 881
Dengue fever traction alopecia, 881
clinical presentation, 289 trichotillomania, 881
epidemiology, 289 hypersensitivity reactions
laboratory test, 289 cutaneous lupus erythematosus, 871–872
treatment, 289 erythema multiforme, 872
Dense deposit disease, 811 Stevens–Johnson syndrome, 870, 872–873
Dental trauma, 634 toxic epidermal necrolysis, 872–873
Denys–Drash syndrome, 454, 455, 809 urticaria, 871
Depressed anterior fontanelle, 44 infestations
Depressed skull fracture with traumatic subdural bedbugs, 866
hemorrhages, 1014 papular urticaria, 866
Depression pediculosis, 865
associated conditions, 185 scabies, 865
CBT strategies, 185 Langerhans cell histiocytosis, 883–884
diagnostic criteria, 184 lichenoid disorders, 867–868
differential diagnosis, 184 melanocytic tumors, 878, 879
interpersonal therapy, 185 papulosquamous disorders
lifestyle modification, 185 pityriasis rosea, 867
male–female ratio, 184 psoriasis, 866–867
management, 185 pearls and pitfalls, 884–885
medications, 185 skin
prognosis, 185, 186 bacterial infections, 874–876
risk factors, 184 viral infections, 873–874
screening and rating scales, 27, 185 skin disorders of newborn
Dermal melanocytosis, 878 diaper dermatitis, 857
1148 Index
Dermatology (cont.) 5 years, 10

erythema toxicum, 855, 856 6 years, 11
miliaria, 855–856 newborn, 4
nevus Sebaceus (of Jadassohn), 856–857 language
transient neonatal pustular melanosis, 855 expressive, 11
vascular malformations, 869, 870 1 month, 5
vascular tumors 2 month, 5
infantile hemangiomas, 868–869 3 month, 5
Kasabach–Merritt phenomenon, 869 4 month, 6
viral infections of the skin, 873–874 6 month, 7
Dermoid cyst, 880 7 month, 7
Descriptive statistics 9 month, 8
absolute risk, 918 12 month, 8
attributable risk, 918 14 month, 9
odds ratio, 917 15 month, 9
relative risk, 918 18 month, 9
reliability (precision), 917 24 month, 10
sample size, 917 3 year, 10
statistical hypothesis, 918–919 4 year, 10
validity (accuracy), 917 5 year, 11
Developmental disorders 6 year, 11
cerebral palsy, 579 receptive, 11
dyskinetic cerebral palsy, 580 primitive reflexes, 11
Rett syndrome, 581 social/communication/problem solving
spastic diplegia, 580 1 month, 5
spastic hemiplegia, 579, 580 2 month, 5
spastic quadriplegia, 580 3 month, 5
Developmental dysplasia of hip (DDH), 53, 476–478, 480 4 month, 6
Developmental screening, 25 6 month, 6
developmental red flags, 14 7 month, 7
fine motor 9 month, 7
1 month, 5 12 month, 8
7 month, 7 3 year, 10
15 month, 9 newborn, 5
18 month, 9 speech intelligibility, 11
24 month, 10 tools, 4
3 year, 10 visual and reflex, newborn, 5
4 year, 10 Diabetes insipidus (DI), 428
5 year, 11 central DI
6 year, 11 causes, 426
block play, 12, 13 clinical presentation, 426
catching objects, 13 diagnosis, 426
climbing stairs, 14 treatment, 426
drawing, 12 definition, 426
social skills, 12 nephrogenic DI
walking and running, 13 causes, 426
following objects, 11 clinical presentation, 426
gross motor diagnosis, 426
1 month, 5 treatment, 426
2 month, 5 Diabetes mellitus (DM), 509
3 month, 5 DKA (see Type 2 Diabetes Mellitus)
4 month, 6 medical evaluation, 461
6 month, 6 MODY, 461
7 month, 7 obesity
9 month, 7 causes, 462
12 month, 8 definition, 462
14 month, 8 obesity-related conditions, 462, 463
15 month, 9 Pediatric Metabolic Syndrome, 462
18 month, 9 treatment, 463
24 month, 9 outpatient management, 461
3 years, 10 type 1 (see Type 1 Diabetes Mellitus)
4 years, 10 type 2 (see Type 2 Diabetes Mellitus)
Index 1149
Diabetic ketoacidosis (DKA) 46 XX females, 452, 453

acidosis resolution, 460 46 XY males, 452
cerebral edema, 233–234 Disseminated gonococcal infection (DGI), 96, 307
classification, 460 Disseminated intravascular coagulopathy, 373
degrees of severity, 232 Distal intestinal obstruction syndrome (DIOS), 781
diagnosis, 232, 460 Distal RTA type I, 814
insulin, 460 Distributive shock, 255–257
monitoring, 461 Diuretics, 938–939
life threatening complications, 234 Divorce, 888
pathophysiology, 232, 233 Dizygotic twins, 55
in pediatric patients, 232–233 Dog bites, 212
precipitating factors, 460 Down syndrome (DS), 114, 510
treatment, 460 abnormalities, 114
Diagnostic errors, 922 audiology referral, 116
Diamond–blackfan anemia car safety seat evaluation, 116
clinical presentation, 356 clinical findings, 113
etiology, 356 clinical investigations, 115
laboratory test, 357 counseling, 115
prognosis, 357 early childhood intervention, 115
treatment, 357 ears-nose-throat/otolaryngology referral, 116
Diaper dermatitis, 857 endocrine referral, 116
Diarrhea eye evaluation, 116
acute diarrhea, 783 hematology referral, 116
antibiotics and drug of, 784 immunizations, 116
chronic diarrhea, 784–785 microarray analysis, 113
clinical presentation, 783 minor anomalies, 115
disaccharide intolerance, 785–786 parental recurrence risk, 113
extraintestinal manifestations, 784 physical examination, 115
management of, 783, 784 physical therapy and exercise, 116
Diastasis recti, 50 prevalence, 113
Diffuse ST elevation, 650 pulmonologist referral, 116
DiGeorge syndrome, 125–126, 673, 674 risk of recurrence, 113
CATCH 22, 409 speech and occupational therapy, 115
clinical presentation, 410 Doxycycline, 291, 305, 306, 313, 314, 319–321, 331, 341
diagnosis, 410 Drowning
prognosis, 410 air-filled swimming aids, 238
treatment, 410 classification, 236
types, 410 definition, 236
Digitalis, 227 disposition, 237
Dilated cardiomyopathy, 684 epidemiology, 236
Diphtheria and tetanus toxoids and acellular management, 236, 237
pertussis vaccine (DtaP), 16 mechanism of injury, 236
Diphyllobothrium latum, 355 personal flotation devices/life jackets, 238
Direct antiglobulin test (DAT) Coombs test, 347 prevention and guidance, 237, 238
Disaccharide intolerance, 785–786 swim lessons, 238
Disciplinary approaches, 888 Drug-induced lupus (DIL), 536
Discoloration of scrotum, 52 Duchenne muscular dystrophy, 572
Disease-modifying antirheumatic drugs Duchenne-Erb palsy, 48
(DMARDs), 531 Duodenal atresia, 773, 969
Disinhibited social engagement disorder, 182–183 Duodenitis, 772
Diskitis, 470 Dwarfism, 131–132
Disorder of pigmentation Dyscalculia, 170
albinism, 876 Dysfunctional uterine bleeding, 93
Café-au-Lait macules, 878 Dysgraphia, 170
dermal melanocytosis, 878 Dyskinetic cerebral palsy, 580
nevus of Ito, 878 Dyslipidemia, 27, 459, 686, 687
nevus of Ota, 878 Dysmenorrhea, 92
pityriasis alba, 876–877 Dysmorphology, 103
post inflammatory hypo/hyper-pigmentation, 877 Dyssomnias, 191
vitiligo, 877 Dystonic reactions, 578
Disorders of sexual development (DSD)
5-alpha-reductase deficiency, 455
AIS, 455 E
ambiguous genitalia, 453 Eagle–Barrett Syndrome, 51, 845–846
CAH (see Congenital adrenal hyperplasia (CAH)) Ear lacerations, 211, 212
causes, 452, 456 Ear, nose, and throat, 1095–1099
Denys–Drash syndrome, 454, 455 Early childhood caries, 633–634
sex chromosome, 453 Early onset breastfeeding jaundice, 58–59
Swyer syndrome, 455 Early term birth, 35
1150 Index
Ears shock (see Shock)

acute mastoiditis, 616 Emergency life support, see Ventilatory support
AOM, 613–614 Emergency medicine, 1044–1049
BPPV, 617 Emotional neglect, 898
cholesteatoma, 616 Encephalitis, 273
CSOM, 615 causes, 336
external ear (Pinna) clinical presentation, 336
foreign body, 612 definition, 336
hematoma, 612–613 diagnosis, 337
labyrinthitis, 616–617 epidemiology, 336
malformed ears, 46 initial evaluation, 336
Meniere’s disease, 618 treatment, 337
otalgia, 611 Endocrinology, 1070–1078
otitis externa, 612 adrenal disorders (see Adrenal disorders)
otitis media with effusion, 614–615 bone and mineral disorders (see Bone and mineral disorders)
preauricular pits/sinus, 611 DM (see Diabetes Mellitus (DM))
recurrent acute otitis media, 614 DSD (see Disorders of sexual development (DSD))
vertigo, 617 growth disorder (see Growth disorder)
Eating disorders, 511 pituitary gland (see Pituitary gland disorder)
anorexia nervosa puberty (see Puberty disorder)
clinical presentation, 89 rickets (see Rickets)
complications, 89 thyroid disorder (see Thyroid disorders)
laboratory, 89 Enteroaggregative E. coli (EAEC), 317
management, 90 Enterobius vermicularis
subtypes, 89 clinical presentation, 332
bulimia diagnosis, 332
clinical presentation, 90 mode of transmission, 331
diagnostic criteria, 90 treatment, 332
management, 90 Enterococcal infections, 301
non-purging subtype, 90 Enterococcus faecalis, 301
purging subtype, 90 Enterococcus faecium, 301
indication of hospitalization, 88 Enterohemorrhagic E. coli (EHEC), 317
morbidity and mortality, 88 Enteroinvasive E. coli (EIEC), 317
suspicious behaviors, 88 Enteropathogenic E. coli (EPEC), 317
Ebstein’s anomaly, 668, 669, 953 Enterotoxigenic E. coli (ETEC), 317
Ecchymoses, 44 Enterovirus
Eclampsia, 42 non-polio virus (see Non-polio virus)
Ectodermal dysplasia, 882–883 poliomyelitis (see Poliomyelitis)
Eczema herpeticum, 273 Enthesitis-related arthritis (ERA), 527
Eczematous dermatitis Environmental safety counseling
acrodermatitis enteropathica, 860 bicycle injuries prevention, 30
atopic dermatitis, 857–859 breathing threats prevention, 30
contact dermatitis, 859 drowning prevention, 29
keratosis pilaris, 859 falls prevention, 30
nickel dermatitis, 860 fire and burns prevention, 29
rhus dermatitis (Poison Ivy), 859 gun accidents prevention, 30
seborrheic dermatitis, 860 mosquito bites prevention, 31, 32
Educational neglect, 898 motor vehicle injuries prevention, 29
Egg allergy, 279, 341 poisoning prevention, 30
Ehlers–Danlos Syndrome (EDS), 135 sunburn injuries prevention, 31
abnormalities, 134, 135 Enzyme-linked immunosorbent assay (ELISA), 403
classical/hypermobile EDS, 134 Eosinophilic esophagitis (EE), 768
diagnosis, 134 Ependymoma, 384
health supervision and preventive care, 135 Epidemiological research methods
prevalence, 134 false negative, 916
vascular EDS, 134 false positive, 915
Ehrlichiosis incidence, 915
clinical presentation, 319 likelihood ratio, 916–917
epidemiology, 319 negative predictive value, 916
laboratory findings, 319 positive predictive value, 916
treatment, 319 prevalence, 915
Electrical burns, 216 sensitivity, 916
Emancipated minors, 83 specificity, 916
Embden–Meyerhof–Parnas pathway, 364 Epidermolysis bullosa (EB), 881–882
Emergency child support Epididymitis (gonococcus), 307
flail chest, 258 Epidural hematoma, 208
hemothorax, 258 Epiglottitis, 309, 310, 703
PARDS (see Pediatric acute respiratory distress syndrome Epilepsy mimics, 558, 559
(PARDS)) Epilepsy syndromes, 557
Index 1151
Epinephrine, 397 subconjunctival hemorrhage, 46

Epispadias, 52 trauma
Epistaxis, 623 clinical evaluation, 600
Erysipelas GAS, 298 closed-globe injuries, 601
Erythema infectiosum, 276, 277 corneal abrasion, 602
Erythema multiforme (EM), 394, 872 eye foreign body, 603
Erythema toxicum, 855, 856 history, 600
Erythroblastosis, 345–348 hyphema, 603
Erythrocytosis open-globe injuries, 601
clinical presentation, 374 orbital fracture, 602
definition, 374 retinal detachment, 601
primary, 374 traumatic iritis, 601
Erythropoietic protoporphyria, 162–163 treatment, 601
Escherichia coli
acute bacterial meningitis, 316
causes, 316 F
enteric infections, 317 Fabry disease, 159
intra-abdominal infections, 317 Facial angiofibromas, 560
pneumonia, 317 Factitious disorders, 884
Esophageal atresia, 771 Failure to pass meconium in 48h of life, 72
Esophageal stenosis, 771 Failure to thrive (FTT), 752
Esophagus Familial adenomatous polyposis (FAP), 789
bezoars, 769 Familial benign hypercalcemia, see Familial hypocalciuric
caustic esophageal injuries, 768 hypercalcemia
eosinophilic esophagitis, 768 Familial hypercholesterolemia, 163
esophageal atresia, 771 Familial hypocalciuric hypercalcemia, 437
esophageal stenosis, 771 Familial mediterranean fever (FMF), 539, 540
foreign body, 769–771 Familial short stature (FSS), 419–421
gastroesophageal reflux, 767, 768 Familial thin basement membrane nephropathy, 813
reflux esophagitis, 771 Family and environmental issues
rumination, 769 cultural issues in medical care, 891, 892
Esotropia, 603, 604 death, 887, 888
Ethics, 1128–1131 discipline, 888
battery, 903 divorce, 888
in cochlear implants, 908 foster care, 890
complementary and alternative medicine, 910, 911 immigrants and internationally adopted
consents, 905–907 children, 890–891
death and dying children, 909 media, 889–890
financial conflict of interest, 911 school refusal, 889
in genetics, 908 separation anxiety disorder, 889
good Samaritan Laws, 903 sibling rivalry and jealousy, 889
imperiled newborn infants, 908–909 Family and societal violence, 895
medical decision-making, 904, 905 Family chip system, 889
medical testimony, 911 Fanconi anemia, 369, 377
negligence and malpractice, 903 clinical presentation, 357
organ donation/transplantation, 909 complications, 358
principles, 903, 904 genetics, 357
research involving children, 909, 910 laboratory findings, 358
Ethnic neutropenia, 368 treatment, 358
Ethylene glycol ingestion, 229 Fats, 740, 741
Ewing sarcoma, 504, 505, 990 Fat-soluble vitamins, 736
Exanthem Subitum, 276 Fatty acid oxidation defects (FAOD)
Exercise-induced asthma (EIA), 711, 712 glutaric acidemia type II, 152
Exercise-induced bronchoconstriction, 509 MCAD, 152
Exfoliative toxins, 292 FDA Adverse Event Reporting System (FAERS), 930
Exotoxin, 292 Febrile neonate, 334
Exotropia, 603, 604 Female athlete triad, 520–521
Extreme low birth weight (ELBW), 35 Female breast masses
Eye foreign body, 603 cystosarcoma phyllode, 91
Eye prophylaxis, 39 fibroadenoma, 91
Eyes indication for surgical intervention, 91
Blue sclera, 46 intraductal papilloma, 91
coloboma, 46 solitary cyst, 91
congenital glaucoma, 46 Female urethral prolapse, 845
congenital myasthenia gravis, 46 Femoral anteversion, 486–487
Horner syndrome, 46 Fetal alcohol syndrome, 77, 78
red reflex examination, 46 Fetal cardiac output, 658
brushfield spots, 46 Fetal distress, 37
strabismus, 46 Fetal macrosomia, 55
1152 Index
Fever, 508 stomach and lower gastrointestinal tract, 232

febrile neonate, 334 symptoms, 231
fever of unknown origin Formula feeding, 744, 745
definition, 335 Foscarnet, 935
differential diagnosis, 335 Foster care, 890
laboratory test, 335 Four square model, 915–916
physical examination, 335 Fractures
treatment, 336 ankle fractures, 499–501
in 1–3 month infants, 334 clavicular fracture, 494
in 3–36 months, 334, 335 compartment syndrome, 500
Fever of unknown origin (FUO), 335, 336 humerus fracture, 495
Fibroadenoma, 91 lateral condyle fracture, 496–497
Fibromatosis colli, 995 medial epicondyle fracture, 497, 498
Fifth disease, see Erythema infectiosum proximal humeral fracture, 494–495
Fitz–Hugh–Curtis syndrome, 306 radial head subluxation, 501–502
Flail chest, 258 Salter–Harris Injuries, 493–494
Flat foot (pes planus), 490–491 scaphoid fracture, 497–499
Flattened nasal bridge, 46 supracondylar fracture of humerus, 495–496
Fluid compartment changes, 826 tibial shaft fracture, 499
Fluid expansion as supportive therapy study (FEAST), 257 toddler fracture, 499, 500
Fluids and electrolytes, 1119, 1120 Fragile X syndrome
body fluid composition, 825 health supervision and preventive care, 128
fluid compartments, 825–826 major abnormalities, 128
hyperosmotic, 826 minor anomalies, 128
hypoosmotic, 826 Francisella tularensis
isosmotic, 826 clinical presentation, 318
Fluorescent in situ hybridization (FISH) test, 109 diagnosis, 318
Fluorescent treponemal antibody absorption (FTA-ABS) test, 321 prevalence, 318
Fluoride, 733 prevention, 318
Fluoroquinolones, 933 treatment, 318
Folate/folic acid, 736 Frasier syndrome, 808
Folic acid deficiency Friedreich ataxia, 576
clinical presentation, 354 Frontal sinus trauma, 626
etiology Fructokinase deficiency, 155
congenital abnormalities, 354 Fructose 1,6-diphosphatase deficiency, 155
decreased folic acid absorption, 354 Full term birth, 35
drug-induced abnormal metabolism, 354 Full thickness burn, 215
inadequate intake, 354 Functional abdominal pain, 757–759
importance, 354 Functional constipation
laboratory test, 354 abdominal radiograph, 774
treatment, 354 anal fissure, 776
Folliculitis, 290, 291 clinical presentation, 774
Fontanelles, 44 definition, 774
Food allergy encopresis, 775, 776
clinical presentation, 399, 400 Hirschsprung disease, 776
diagnosis, 400 non-functional causes of, 775
mechanism, 399 rectal prolapse, 777
prognosis, 400 treatment, 775
treatment, 400 and withholding, 774
Foodborne botulism Functioning ectopic gastric mucosa
clinical presentation, 302 (Meckel’s diverticulum), 973
incubation period, 302 Fungal infections
treatment, 302 Aspergillus species
Foot disorders causes, 327
calcaneovalgus foot, 489–490 clinical presentation, 327
cavus foot, 490 diagnosis, 327
clubfoot (talipes equinovarus), 489 mode of transmission, 327
flat foot (pes planus), 490–491 treatment, 327
ingrowing toenail, 493 Blastomyces, 328
tarsal coalition, 491–492 Candida (see Candida species)
tip-toe walking, 492 coccidioidomycosis
Foreign body, 770 clinical presentation, 328
Foreign body (FB) aspiration, 706, 955 diagnosis, 328
lower airway, 231 mode of transmission, 328
upper airway, 231 histoplasmosis
Foreign body ingestion clinical presentation, 328
esophagus, 231 mode of transmission, 327
Index 1153
Malassezia furfur, 327 multifactorial determination, 107

onychomycosis, 865 X-Linked Inheritance, 106–107
Sporothrix schenckii, 328 Genetic nonsyndromic hearing loss, 619–620
tinea capitis, 862, 863 Genetic screening
tinea corporis, 863 maternal blood screening, 112
tinea cruris, 864 noninvasive pregnancy testing, 112
tinea pedis, 864 preconception screening, 112
tinea versicolor, 864 preimplantation genetic diagnosis, 112
Furuncles, 290 Genetic syndromic hearing loss, 619
Genetic testing
amniocentesis, 112
G chorionic villus sampling, 112, 113
GABHS rapid antigen test, 626 chromosome analysis/karyotyping, 109
Galactosemia clinical applications, 110–112
clinical presentation, 153 DNA testing, 109
complications, 153 FISH test, 109
diagnosis, 153 gene panel sequencing, 110
treatment, 153 genetic screening, 112
Ganciclovir (IV), 935 genome sequencing, 110
Gastric lavage, 222 metabolic testing, 109
Gastroenteritis, 838 phenotypic testing, 109
Gastroenterology, 1110–1115 postnatal genetic testing, 110
Gastroesophageal reflux (GER), 698 presymptomatic genetic testing, 110
Gastrointestinal bleeding single gene sequencing, 110
esophageal varices, 786–787 Genital herpes, 273
lower bleeding, 787 Genitourinary radiology
Meckel diverticulum, 787–788 acute right testicular torsion, 983
upper bleeding, 786 adrenal hemorrhage, 981
Gastrointestinal radiology autosomal recessive polycystic kidney disease, 980
acute appendicitis, 966 hematometrocolpos, 982
biliary atresia, 972 infected patent urachus, 978
bowel perforation with pneumoperitoneum, 963 left grade IV and right grade III vesicoureteral reflux, 979
button battery ingestion, 974 posterior urethral valve, 978
Crohn’s disease with terminal ileitis, 976 rhabdomyosarcoma of the bladder, 983
duodenal atresia, 969 right ovarian torsion, 982
functioning ectopic gastric mucosa (Meckel’s diverticulum), 973 tubo-ovarian abscess, 984
Hirschsprung disease, 970 Wilms tumor, 981
hypertrophic pyloric stenosis, 965 Genodermatoses
ileocolic intussusception, 968 ectodermal dysplasia, 882–883
incarcerated inguinal hernia, 971 epidermolysis bullosa, 881–882
malrotation with volvulus, 967 ichthyosis vulgaris, 883
meconium peritonitis, 964 incontinentia pigmenti, 882
neuroblastoma, 977 Genomic imprinting, 108
pneumatosis intestinalis, 962 Genu valgum (knock-knee), 485
portal venous gas, 962 Genu varum (Bowleg), 484–485
small bowel obstruction, 975 Germ cell tumors
Gastroschisis, 51 clinical presentation, 385
Gaucher disease, 157–158 diagnosis, 385
Gender identity disorder (GID), 192 laboratory test, 385
General pediatrics, 1016–1022 treatment, 385
Generalized anxiety disorders, 180 types, 385
Generalized cyanosis, 43 Gestational age (GA), 35, 53, 54
Genitalia Gestational diabetes mellitus (GDM)
ambiguous genitalia, 52–53 definition, 42
anus, 53 management, 42
female infants, 52 risk of, 42
males Gianotti-Crosti syndrome, 793
penis, 52 Giardia lamblia, 329
testis, 52 Giardiasis
Genetic anticipation, 108 clinical presentation, 329
Genetic disorders, 1032–1036 diagnosis, 329
autosomal dominant inheritance, 104–105 mode of transmission, 329
autosomal recessive inheritance, 105–106 treatment, 329
chromosomal inheritance, 103, 104 Gifted child, 891–892
genetic anticipation, 108 Gigantism, 136–138, 428
genomic imprinting, 108 Gilbert syndrome, 60, 791, 792
major anomalies, 103 Gingivostomatitis, 273
minor anomalies, 103 Gitelman syndrome, 815
mitochondrial inheritance, 108 Glanzmann thrombasthenia, 373
1154 Index
Glasgow Coma Scale (GCS) score, 220 clinical manifestations, 304

Glaucoma, 594 E. coli O157
Global hypoxic ischemic injury, 1004 clinical presentation, 317
Glomerular hematuria, 800, 801 incidence, 317
Glucose-6-phosphate dehydrogenase treatment, 317
(G6PD) deficiency urinary tract infections, 317
clinical presentation, 365 ehrlichiosis
genetics, 365 clinical presentation, 319
incidence, 365 epidemiology, 319
laboratory test, 366 laboratory findings, 319
pathophysiology, 365 treatment, 319
treatment, 366 Escherichia coli
Glutaric aciduria type I/glutaric acidemia, 147–148 acute bacterial meningitis, 316
Gluten-sensitive enteropathy, 779, 780 causes, 316
Glycine encephalopathy, 150 enteric infections, 317
Goldenhar syndrome/hemifacial microsomia, 138 intra-abdominal infections, 317
Gonococcal conjunctivitis, 586 pneumonia, 317
Gonococcal pharyngitis, 307 Francisella tularensis
Gonococcal proctitis, 307 clinical presentation, 318
Gonococcal urethritis, 307 diagnosis, 318
Good Samaritan laws, 903 prevalence, 318
Goodpasture syndrome, 812 prevention, 318
Grade IV intraventricular hemorrhage, 997 treatment, 318
Gram-negative bacteria Haemophilus influenzae
Bartonella henselae bacterial meningitis, 309
clinical presentation, 313 buccal infections, 310
diagnosis, 313 causes, 309
source, 313 epiglottitis, 309, 310
surgical treatment, 314 occult bacteremia, 310
treatment, 313, 314 periorbital cellulitis, 310
Bordetella pertussis pneumonia, 310
catarrhal phase, 311 pyogenic arthritis, 310
convalescent phase, 311 rifampin antibiotic prophylaxis, 310
diagnosis, 312 treatment, 310
immunization, 312 Klebsiella, 314
incubation period, 311 mycobacterium avium-intracellulare, 325
paroxysmal phase, 311 Mycoplasma pneumonia
pertussis complications, 311 clinical presentation, 310
prophylaxis, 312 incubation period, 310
thoracic pressure-related complications, 312 testing for mycoplasma, 311
Borrelia burgdorferi N. meningitidis
early disseminated disease stage II, 320 prevention and indications, 309
early localized disease stage I, 320 symptoms, 308
incubation period, 320 transmission rate, 308
late disseminated disease stage III, 320 treatment, 309
treatment, 320 Neisseria gonorrhoeae
brucellosis disseminated gonococcal infection, 307
causes, 312 epididymitis (gonococcus), 307
diagnosis, 312 gonococcal pharyngitis, 307
risks, 312 gonococcal proctitis, 307
treatment, 313 gonococcal urethritis, 307
Campylobacter species incubation period, 307
clinical presentation, 304 neonatal conjunctivitis, 307
diagnosis, 305 screening, 308
epidemiology, 304 nontyphoidal salmonellosis
treatment, 305 antibiotic therapy, 315
chlamydia genitourinary tract infection, 306 clinical presentation, 315
Chlamydia pneumoniae diagnosis, 315
clinical presentation, 305 incubation period, 314
diagnosis, 305 mode of transmission, 315
epidemiology, 305 Pasteurella multocida
Chlamydia trachomatis risk, 311
conjunctivitis due to, 305 treatment, 311
pneumonia due to, 306 Pseudomonas species
Chlamydophila psittaci, 305 antimicrobial therapy, 314
Citrobacter, 314 causes, 314
Index 1155
clinical presentation, 314 methicillin-resistant S. aureus, 293

risk factors, 314 methicillin-sensitive S. aureus, 293
RMSF (see Rocky mountain spotted fever (RMSF)) necrotizing fasciitis
Shigella aerobic and anaerobic flora, 299
child care center, 316 clinical presentation, 300
complications, 316 laboratory findings, 300
incubation period, 316 PANDAS, 299
mode of transmission, 316 perianal streptococcal dermatitis
TB (see Mycobacterium tuberculosis) diagnosis, 298
trachoma, 306, 307 incidence, 298
Treponema pallidum, 320, 321 treatment, 298
typhoid fever S. aureus food poisoning
diagnosis, 315 incubation period, 292
mode of transmission, 315 treatment, 292
treatment, 315 S. pneumoniae
Yersinia enterocolitica, 318 clinical manifestations, 294
Gram-positive bacteria diagnosis, 294
Arcanobacterium haemolyticum, 301, 302 epidemiology, 294
Bacillus anthracis, 301 risks, 294
Bacillus cereus treatment, 294, 295
clinical presentation, 301 scarlet fever
GI tract, 301 clinical presentation, 296, 297
Clostridium botulinum streptococcosis, 297
causes, 302 treatment, 297
clinical presentation, 302 SSSS
diagnosis, 302 clinical presentation, 292
infant botulism, 302 diagnosis, 292
Clostridium difficile staphylococcal infections, 290
clinical presentation, 303 staphylococcal, coagulase-negative, 293
diagnosis, 304 Staphylococci in blood culture, 290
prevention, 304 streptococcal toxic shock syndrome, 299
risk factor, 303 clinical presentation, 299
Clostridium perfringens, 302, 303 risk factors, 299
Clostridium tetani treatment, 299
common sources, 303 TSS
generalized tetanus, 303 clinical presentation, 291
neonatal tetanus, 303 production, 291
prevention, 303 risk factors, 291
treatment, 303 treatment, 291, 292
Corynebacterium diphtheriae, 300 Granuloma annulare (GA), 879–880
enterococcal infections, 301 Granulomatosis infantisepticum, 300
epidemiology, 289, 290 Granulomatosis with polyangiitis (GPA), 543, 544
erysipelas GAS, 298 Graves disease, 431, 432
folliculitis/furunculosis/carbunculosis, 290 Grisel syndrome, 472
antibiotics, 290 Group A beta-hemolytic Streptococcus
oral anti-staphylococcal antibiotics, 290 (GAS) pharyngitis
recurrent staphylococcal skin infections, 291 clinical presentation, 295
foodborne botulism diagnosis, 296
clinical presentation, 302 epidemiology, 295
incubation period, 302 treatment, 296
treatment, 302 Group B streptococcal (GBS) infection
GAS pharyngitis clinical presentation, 69
diagnosis, 296 early GBS, 68
epidemiology, 295 intrapartum prophylaxis, 69
treatment, 296 late GBS, 68
impetigo prevention guidelines, 69, 70
clinical presentation, 297 screen timing, 69
etiology, 297 secondary prevention, 69
Listeria monocytogenes, 300 Growing pains, 541, 542
1156 Index
Growth craniosynostosis, 567

abnormal growth diagnosis, 1 hydrocephalus, 566, 567
genetic growth, 1 macrocephaly, 566
growth charts, 1 microcephaly, 566
growth curve reading, 2 Head trauma
head circumference, 2 basilar skull fracture, 207
height, 1 CT, 208
length or supine height measurement, 1 epidural hematoma, 208
weight, 1 management, 208–209
Growth disorder mechanisms of injury, 206
constitutional delay of growth and puberty, 419, 420 patients at higher risk, 207
familial short stature, 419–421 retinal hemorrhage, 208
idiopathic short stature, 420 subarachnoid bleed, 208
normal growth rate, 417, 418 subdural hematoma, 207–208
psychosocial dwarfism, 421 temporal skull fracture, 207
short stature Headache
bone age radiograph, 419 chronic nonprogressive headache, 562
history, 418 chronic progressive headache, 562
laboratory evaluation, 419 epidemiology, 561
normal variant, 417 idiopathic intracranial hypertension, 563, 564
pathological, 417 migraine headache, 561
physical examination, 418 post-traumatic/post-concussion headaches, 563
Guillain–Barré syndrome (GBS), 337, 546, 572, 573 primary headache syndromes
Gynecomastia, 94, 447 diagnosis, 562
treatment of, 562, 563
red flags, 562
H tension headache, 561
Habit disorder types of, 561
general management, 184 Hearing aids, 622
hair-pulling disorder, 183 Hearing loss
nail biting, 184 audiogram, 621
teeth grinding, 183 bone-anchored hearing aid, 622
thumb sucking, 183, 184 cochlear implants, 622
trichotillomania, 183 congenital hearing loss, 618–619
Haemophilus influenzae genetic nonsyndromic hearing loss, 619–620
bacterial meningitis, 309 genetic syndromic hearing loss, 619
buccal infections, 310 hearing aids, 622
causes, 309 hereditary hearing loss, 622
epiglottitis, 309 middle ear effusion, 621
occult bacteremia, 310 ototoxicity, 621
periorbital cellulitis, 310 pediatric audiometric testing, 620–621
pneumonia, 310 sound amplification devices, 622
pyogenic arthritis, 310 tympanic membrane perforation, 621
rifampin antibiotic prophylaxis, 310 types, 618
treatment, 310 Hearing screening, 25
Haemophilus Influenzae Type B (Hib) conjugate, 17 Heart
Hair disorders blood pressure, 50
alopecia areata, 880–881 bradycardia, 50
anagen effluvium, 881 murmur, 50
telogen effluvium, 881 point of maximal cardiac impulse, 49
traction alopecia, 881 tachycardia, 50
trichotillomania, 881 failure, 753, 754
Hair-pulling disorder, 183 causes, 682, 683
Hall–Pallister syndrome, 423 clinical presentation, 683
Hand, foot, and mouth disease, 282, 283 diagnostic evaluation, 683
Handicapping conditions, 893, 894 management, 683, 684
Harlequin ichthyosis, 44 murmur, 509
Hashimoto thyroiditis, 430 Heat illness, 511
Hawthorne effect, 913 Helicobacter pylori, 395
Head Helminthic organism
caput succedaneum, 45 Ascaris lumbricoides
cephalohematoma, 45 clinical presentation, 332
fontanelles, 44 diagnosis, 332
head shape, 44 mode of transmission, 332
skull fractures, 45 treatment, 332
subgaleal hemorrhage, 45 cestodes (platyhelminthes), 333
traumatic epidural, subdural and subarachnoid hemorrhage, 45 Enterobius vermicularis
Head growth disorders clinical presentation, 332
Index 1157
diagnosis, 332 etiology, 359

mode of transmission, 331 laboratory test, 360
Necator americanus Herpes gladiatorum, 273, 274
clinical presentation, 332 Herpes simplex virus (HSV) conjunctivitis, 588–589
mode of transmission, 332 Herpes zoster (shingles), 275
treatment, 332 Herpetic whitlow, 273
Strongyloides stercoralis, 333 Heterophile antibody test, 272
toxocariasis, 333 High-efficiency particulate air (HEPA) filter, 268
trematodes (platyhelminthes), 333 Hip disorders
Trichinella spiralis, 333 developmental dysplasia of the hip, 476–478
trichuriasis, 332 Legg–Calve–Perthes Disease, 478–479
Hemangioma, 606–607 slipped capital femoral epiphysis, 479, 480
Hematology/oncology, 1060–1066 Hirschsprung disease (HD), 776, 970
Hematoma, 612–613 Histoplasmosis, 327, 328
Hematometrocolpos, 982 History and physical examination, 247, 248
Hematuria, 800 HIV infection, 509
Hemihypertrophy, 53 HIV screening, 26–27
Hemolytic anemia Hodgkin lymphoma
AIHA (see Autoimmune hemolytic anemia (AIHA)) clinical presentation, 380
G6PD deficiency (see Glucose-6-phosphate dehydrogenase diagnosis, 380
(G6PD) deficiency) incidence, 379
hereditary elliptocytosis, 360 prognosis, 380
hereditary spherocytosis (see Hereditary spherocytosis) treatment, 380
PK deficiency (see Pyruvate kinase deficiency) Holt-Oram syndrome, 662, 674
PNH (see Paroxysmal nocturnal hemoglobinuria (PNH)) Home-prepared baby foods, 746
SCD (see Sickle cell disease) Homocystinuria
Hemolytic uremic syndrome (HUS), 372, 800, 821, 822 clinical presentation, 149
Hemophagocytic lymphohistiocytosis (HLH), 276 diagnosis, 149
Hemoptysis, 701, 702 and Marfan syndrome, 149
Hemorrhagic conjunctivitis, 587 prognosis, 149
Hemorrhagic disease treatment, 149
classic stage, 62 Homosexuality, 192
clinical presentation, 62 Hookworm, 332
diagnosis, 62 Hordeolum (Stye), 591–592
early stage, 62 Horner syndrome, 46
late stage, 62 Hot tub folliculitis, 290
of newborn, 373 Human bites, 212
prevention, 62 Human herpesvirus type 6 (HHV-6)
Hemothorax, 258 treatment, 276
Henoch-Schönlein purpura (HSP), 545–547 Human herpesvirus-7 (HHV-7), 276
Hepatic dysfunction, 249 Human herpesvirus-7 (HHV-8), 276
Hepatic metabolism, 927–928 Human immunodeficiency virus (HIV)
Hepatitis A (HepA) vaccine, 20–21 clinical presentation, 284, 285
Hepatitis A virus (HAV), 792, 793 diagnosis
Hepatitis B prophylaxis, 39 adult and adolescent infection, 285
Hepatitis B Vaccine (HepB) vaccination, 15–16 children, 285
Hepatitis B virus (HBV), 793–795 perinatal and postnatal infection, 285
Hepatitis C virus (HCV), 795–796 incubation period, 284
Hepatoblastoma mode of transmission, 284
associated syndromes/risk factors, 385 prevention, 285, 286
clinical presentation, 385 Human metapneumovirus
incidence, 384 epidemiology, 280
Hepatomegaly, 796, 797 Human papillomavirus (HPV)
Hepatorenal tyrosinemia, 150 clinical features, 289
Hereditary angioedema (HAE) epidemiology, 289
clinical presentation, 397 immunization, 289
diagnosis, 397 vaccines, 22, 23
treatment, 397 Humerus fracture, 495
types, 396 Hunter syndrome, 156
Hereditary elliptocytosis, 360 Hurler syndrome, 156
Hereditary hearing loss, 622 Hydrocarbon ingestion, 230
Hereditary motor sensory neuropathy (HMSN), 573 Hydroceles, 850
Hereditary spherocytosis Hydrocephalus, 2, 566, 567
clinical presentation, 359 Hyperaldosteronism, 449
1158 Index
Hyperammonemia, 144 Hyponatremia, 829–831

Hyperbilirubinemia, 56, 790 Hyponatremic dehydration, 832
ABO and Rh incompatibility, 61 Hypoparathyroidism
chronic bilirubin encephalopathy, 61 causes, 436
conjugated hyperbilirubinemia, 60 clinical presentation, 436
early onset breastfeeding jaundice, 58–59 diagnosis, 436
kernicterus, 60–61 treatment, 436
late onset breast milk jaundice, 59 Hypophosphatemic rickets, 441
management Hypoplastic left heart syndrome (HLHS), 674
exchange transfusion, 62 Hypospadias, 52, 846
feeding, 61 Hypothermia, 251
intravenous immunoglobulin, 62 Hypotropia, 603
phototherapy, 61, 62 Hypovolemic shock, 254–255
pathophysiology, 57 Hypoxanthine-guanine phosphoribosyltransferase deficiency, 163
physiologic jaundice Hypoxic-ischemic encephalopathy (HIE)
causes, 58 clinical and laboratory evidence, 75
clinical presentation, 58 clinical presentation, 75, 76
risk factors, 58 imaging studies, 76
TSB concentrations, 57, 61 laboratory studies, 76
unconjugated hyperbilirubinemia, 60 management, 76
Hyper-IgE syndrome (HIES) pathogenesis, 75
clinical presentation, 411
diagnosis, 411
DOCK8, 411 I
treatment, 411 Ibuprofen ingestion, 225
Hyperkalemia, 834, 835 Ichthyosis vulgaris, 883
Hypernatremia, 827–829 Idiopathic hypercalciuria, 801, 802
Hyperosmolar nonketotic coma, 838–839 Idiopathic intracranial hypertension, 563, 564
Hyperosmolar therapy, 251 Idiopathic short stature (ISS), 420
Hyperparathyroidism, 437, 438 IgA nephropathy, 809, 810
Hyperpituitarism Ileocolic intussusception, 968
acromegaly, 428 Imerslund-Gräsbeck syndrome, 355
gigantism, 428 Immersion burns, 896
prolactinoma, 428 Immigrants, 890–891
Hypersensitivity reactions Immune system
cutaneous lupus erythematosus, 871–872 adaptive immune system, 404
erythema multiforme, 872 B-cells, 404, 405
Stevens–Johnson syndrome, 870, 872–873 innate immune system, 404
toxic epidermal necrolysis, 872–873 T-lymphocytes, 404
urticaria, 871 Immune thrombocytopenic purpura (ITP), 372
Hypertension, 802–804 Immunization
Hypertensive crisis common adverse reaction, 22
BP measurement, 238 contraindications, 23
emergency care, 239, 240 DtaP vaccine, 16
hypertensive emergency, 238 Hib conjugate, 17
hypertensive urgency, 238 HepA vaccine, 20–21
primary hypertension, 238 HepB, 15–16
secondary causes, 238, 239 HPV vaccines, 22, 23
secondary hypertension, 238 IPV, 18
Hypertensive urgency, 238 influenza vaccines, 19
Hyperthermia, 1026 meningococcal conjugate vaccines, 21–22
Hypertrophic cardiomyopathy (HCM), 651, 685 MMR vaccine, 19–20
Hypertrophic pulmonary osteodystrophy, 701 pneumococcal vaccines, 17–18
Hypertrophic pyloric stenosis, 965 refusal by parents, 15
Hypertropia, 603 risks and benefits, 15
Hyperventilation, 251 rotavirus vaccine, 16
Hyphema, 603 schedule, 15
Hypocalcemia Tdap vaccine, 16, 17
causes, 434 VAR vaccine, 20
clinical presentation, 435 VariZIG, 20, 21
definition, 434 Imperforate hymen, 93
diagnosis, 435 Imperiled newborn infants, 908–909
treatment, 435, 436 Impetigo, 297, 874–875
Hypochloremia, 835 clinical presentation, 297
Hypochromic/microcytic anemia, 349, 350 etiology, 297
Hypoglycemia, management of, 56–57 treatment, 298
Hypokalemia, 835 Inactivated poliovirus vaccine (IPV), 18
Index 1159
Incarcerated inguinal hernia, 971 Intellectual disability (ID)

Incontinentia pigmenti, 882 causes, 167
Individualized Education Plans (IEPs), 894 classification, 167
Infantile colic, 32 clinical presentation, 167
Infantile hemangiomas (IH), 868–869 differential diagnosis, 168
Infantile hypertrophic pyloric stenosis (HPS), 773 management, 168
Infantile nephrotic syndrome, 807, 808 prevalence, 167
Infantile nystagmus syndrome, 606 Intention-to-treat analysis, 919
Infantile spasms, 552 Intermittent exotropia, 604
Infants of diabetic mother (IDM) Internal tibial torsion, 487–488
complications International Diabetes Federation Criteria, 462
cardiovascular anomalies, 56 Internationally adopted children, 890–891
congenital malformations, 56 Interstitial edema, 252
fetal macrosomia, 55 Intertrigo, 875–876
hyperbilirubinemia, 56 Intestinal polyposis syndromes, 788–789
hypocalcemia/hypomagnesemia, 56 Intoeing
impaired fetal growth, 55 femoral anteversion, 486–487
iron deficiency, 56 internal tibial torsion, 487–488
metabolic and electrolyte abnormalities, 56 metatarsus adductus, 488
polycythemia, 56 Intracranial pressure (ICP), 563
pulmonary disease, 56 cerebral edema, 251, 252
thrombocytopenia, 56 clinical presentation, 249
congenital malformations, 55 dexamethasone, 251
fetal hyperglycemia, 55 hyperosmolar therapy, 251
fetal hyperinsulinemia, 55 hyperventilation, 251
preconceptional glycemic control, 55 hypothermia, 251
Infected patent urachus, 978 management of, 250
Infectious diseases, 1052–1060 measures for intubated patients, 250
bacterial pathogens (see Gram-negative bacteria) (see Gram- symptoms, 249
positive bacteria) Intraductal papilloma, 91
CNS (see Central nervous system (CNS) infections) Intrauterine growth retardation (IUGR)
fever (see Fever) asymmetrical IUGR, 54
fungal infection (see Fungal infections) definition, 54
helminthic organism (see Helminthic organism) diagnosis, 55
prevention (see Prevention of infectious diseases) fetal factors, 54
protozoa infection (see Protozoa) maternal factors, 54
viral infections (see Viral infections) placental factors, 54
Infectious mononucleosis, 635 symmetrical IUGR, 54
Infective endocarditis (IE), 678, 679 Intravenous rehydration, 828, 831
Infestations Intraventricular hemorrhage (IVH)
bedbugs, 866 classification, 76
papular urticaria, 866 clinical presentation, 76
pediculosis, 865 complication, 77
scabies, 865 diagnosis, 76
Inflammatory bowel disease (IBD), 532, 777–779 prevention, 77
Inflammatory myopathies prognosis, 77
JDM, 537, 538 risk factors, 76
polymyositis, 538 Intussusception, 763
Influenza vaccines, 19 Iodine, 733
Influenza virus Ipecac, 222
AAP immunization guidelines, 279 Iron, 733, 734
clinical presentation, 278 Iron deficiency anemia screening, 26
complications, 278, 279 Iron ingestion, 229
diagnosis, 279 Isolated (benign) premature thelarche, 442
epidemiology, 278 Isolated beta-methylcrotonyl-CoA carboxylase
treatment, 279 deficiency, 147
Ingrowing toenail, 493 Isolated sagittal craniosynostosis, 1013
Inguinal hernia, 851 Isonatremic dehydration, 834
Inherited bleeding disorders Isovaleric acidemia, 145
hemophilia A and B, 374
Von Willebrand disease, 374
Inpatient pneumonia, 295 J
Insect sting allergy Janeway lesion, 678
anaphylactic reactions, 401 Jaundice, 44
diagnosis, 402 Jealousy, 889
large local reactions, 401–402 Jejunal atresia, 774
systemic cutaneous reactions, 401 Jervell Lange–Nielsen syndrome, 619
treatment, 402 Jeune syndrome, 782
1160 Index
Johanson-Blizzard syndrome, 781 L

Juvenile dermatomyositis (JDM), 537, 538 Labyrinthitis, 616–617
Juvenile idiopathic arthritis (JIA), 526, 590 Laceration
complications of, 530 anesthetic and anxiolytic options, 211
definitions, 525 animal and human bites
ERA, 527 antibiotic therapy, 212, 213
imaging, 530 bat bites, 212
laboratory abnormalities, 529, 530 black widow spider bite, 214
MAS, 529 brown recluse spider bite, 214–215
oligoarticular, 526, 527 cat bites, 212
polyarticular, 527 dog bites, 212
psoriatic, 528 general evaluation, 212
systemic-onset, 528 imaging studies, 213
treatment of, 530, 531 laboratory, 213
uveitis, 529 management, 212
Juvenile myoclonic epilepsy, 554 rabies prophylaxis indications, 213
Juvenile pilocytic astrocytoma scorpion stings, 215
(JPA), 383, 1006 snake bites (see Snake bites)
Juvenile polyposis syndrome (JPS), 788 tetanus vaccine, 212
Juvenile systemic lupus types of human bite injuries, 212
erythematosus (jSLE), 533 wound care, 213
APS, 534 common locations, 210
cardiac manifestations, 534 definition, 210
clinical presentation, 532 ear lacerations, 211, 212
cutaneous manifestations, 532, 533 lip lacerations, 211
endocrine manifestations, 534 nail bed lacerations, 211
gastrointestinal manifestations, 534 prophylactic antibiotics, 211
general manifestations, 532 suture and staples, 211
hematologic involvement, 534 suture removal timing, 212
laboratory evaluation, 534, 535 wound aftercare, 211
management, 535 wound preparation, 211
musculoskeletal manifestations, 533 Lack of systemic arterial supply, 950
neuropsychiatric manifestation, 533 Landau–Kleffner syndrome, 554, 555
pulmonary manifestations, 534 Langerhans cell histiocytosis (LCH), 883–884
renal manifestations, 533 clinical presentation, 381
diagnosis, 381
differential diagnosis, 381
K incidence, 381
Kaposi sarcoma, 276 prognosis, 382
Kasabach-Merritt phenomenon, 869 treatment, 381
Kawasaki disease (KD), 643, 675–678 Language disorders, 169
Keratosis pilaris, 859 Large fontanelles, 44
Kernicterus Large for gestational age (LGA), 35
BIND, 60 Laryngeal web, 696
causes, 60 Laryngomalacia, 640–641, 695
clinical features, 60 Laryngotracheoesophageal cleft, 697
phase 1, 60 Late onset breast milk jaundice, 59
phase 2, 61 Late term birth, 35
phase 3, 61 Latent tuberculosis infection (LTBI), 321, 323–325
Kernig and Brudzinski signs, 338 Lateral condyle fracture, 496–497
Kidney stones, 851, 852 Laurence–Moon–Bardet–Biedl syndrome, 818, 819
Kikuchi, 636 Lead poisoning, 353
Kinky hair disease, 164 Lead screening, 25–26
Klebsiella, 314 Learning disorders
Kleihauer–Betke (KB) test, 345 aptitude-achievement discrepancy, 170
Klinefelter syndrome, 119, 447 associated conditions, 170
health supervision and preventive care, 119 ADHD (see Attention-deficit/hyperactivity
neurobehavioral abnormalities, 118 disorders (ADHD))
physical and medical abnormalities, 118, 119 earlier signs, 170
routine karyotype or microarray analysis, 118 etiology, 170
Klippel–Feil syndrome, 472 management, 170, 171
Klippel–Trenaunay syndrome, 782 mathematics (dyscalculia), 170
Klumpke palsy, 48 poor school performance, 171
Knee pain and injuries reading disorders, 170
anterior cruciate ligament injury, 482 screening, 170
medial collateral ligament injury, 482 written expression (dysgraphia), 170
meniscal injury of the knee, 480–482 Left grade IV and right grade III
osteochondritis dissecans, 483 vesicoureteral reflux, 979
recurrent patellar dislocation/subluxation, 483, 484 Left parietal calcified cephalohematoma, 1009
Krabbe disease, 158 Legg–Calve–Perthes disease (LCPD), 478–480
Index 1161
Leg-length discrepancy, 466 M

Lennox–Gastaut syndrome, 554, 555 Macrocephaly, 137, 566
Leri-Weill dyschondrosteosis short stature benign familial macrocephaly, 2
syndrome, 120 causes, 2
Lesch–Nyhan disease, 163 definition, 2
Leukocyte adhesion defect hydrocephalus, 2
clinical presentation, 407 Macrocytic anemia
diagnosis, 407 diamond–blackfan anemia
treatment, 407 clinical findings, 356, 357
Leukocytosis, 367, 375, 376, 388 clinical presentation, 356
Lichen nitidus, 867 etiology, 356
Lichen sclerosus, 867–868 laboratory test, 357
Lichenoid disorders, 867–868 prognosis, 357
Li–Fraumeni, 384 treatment, 357
Likelihood Ratio (LR), 916–917 fanconi anemia
Limping child, 465, 466 clinical findings, 356
Lip lacerations, 211 clinical presentation, 357
Lipidoses, 160 complications, 358
Fabry disease, 159 genetics, 357
Gaucher disease, 157–158 laboratory findings, 357
Krabbe disease, 158 treatment, 358
metachromatic leukodystrophy, 159–160 folic acid deficiency
Niemann–Pick disease, 158 clinical presentation, 354
Tay–Sachs disease, 158–159 etiology, 354
Wolman syndrome, 159 importance, 354
Lissencephaly, 565 laboratory test, 354
Listeria monocytogenes, 300 treatment, 354
Little Leaguer’s elbow, 516 Pearson marrow–pancreas syndrome, 356
Little Leaguer’s shoulder, 516 Shwachman-Diamond syndrome
Live birth, 35 clinical presentation, 358
Liver, 50 complications, 358
AIH, 796 diagnosis, 358
Alagille syndrome, 792 genetics, 358
biliary atresia, 790–791 laboratory findings, 358
Gilbert syndrome, 791, 792 treatment, 358
HAV, 792, 793 vitamin B12 deficiency
HBV, 793–795 clinical presentation, 355
HCV, 795, 796 etiology, 355
hepatomegaly, 796, 797 laboratory test, 355, 356
jaundice, 789 sources, 354
neonatal cholestasis, 790 treatment, 356
portal hypertension, 797 Macroglossia, 47, 697
Wilson disease, 791 Macrolides, 932–933
Lobar pneumonia, 957 Macronutrients
Localized scleroderma, 536, 537 calories/energy, 740
Lonestar tick (Amblyomma americanum), 319 carbohydrates, 741
Long gap esophageal atresia with fats, 740, 741
tracheoesophageal fistula, 952 protein, 741
Low birth weight (LBW), 35 Macrophage-activation syndrome (MAS), 528, 529
Lower airway infection, 199 Magnesium, 734
Lower airway obstruction, 199 Malaria
Lower motor neuron facial nerve palsy, 574 clinical presentation, 331
Lower motor neuron lesions (LMNL), 571 complications, 331
Lung diagnosis, 331
cough, 49 prevention, 331
respiratory distress, 49 treatment, 331
unilateral movement of chest, 49 Malassezia furfur, 327
Lupus nephritis (LN), 812 Malformed ears, 46
Lyme disease, 319, 320 Malignant hyperthermia (MH), 248
Lymphadenitis, 636 Malnutrition
Lymphocytic thyroiditis, 430 allergies, 755
Lymphogranuloma venereum (LGV), 306 burns, 754
Lymphoma, 636–637, 961 chronic liver disease, 753
Lysosomal storage disorders cystic fibrosis, 753
lipidoses, 157–160 family and cultural practices, 755
MPS heart failure, 753, 754
type I, 156 malignancies, 754
type II, 156 neurological impairment, 755
type III, 156–157 renal disease, 754
type IV, 157 viral gastroenteritis, 753
1162 Index
Malrotation, 762 Meniere’s disease, 618

Malrotation with volvulus, 967 Meningitis
Maple syrup urine disease (MSUD), 146 child care, 340
Marfan syndrome, 133, 149, 674 clinical manifestations, 338
abnormalities, 132, 134 corticosteroids in bacterial meningitis, 340
clinical diagnosis, 132 diagnosis, 338, 339
health supervision and preventive care, 134 drugs, 339
prevalence, 132 N. meningitidis, 338
Marrow suppression, 372 neonatal gram-negative meningitis, 337
Mastocytosis, 880 neonatal herpes simplex infection, 337
clinical presentation, 396 neonatal meningitis due to listeria, 337
cutaneous, 395 neonatal streptococcal meningitis, 337
diagnosis, 396 physical examination, 338
prognosis, 396 prognosis, 340
systemic, 395 S. pneumoniae, 338
Masturbation, 191–192 Meningocele, 569
Maternal blood screening, 112 Meningococcal conjugate vaccines (MCV), 21–22, 270
Mature breast milk, 742–744 administration, 22
Maturity-onset diabetes of youth (MODY), 461 catch-up vaccination, 21
McCune–Albright syndrome, 445, 446 Menactra, 21, 22
McMurray test, 481 Menveo, 21, 22
Measles virus routine vaccination, 21
clinical presentation, 286 Serogroup B meningococcal vaccines, 22
control and prevention, 286 Meningococcal infections, see Neisseria meningitidis
diagnosis, 286 Meniscal injury of the knee, 480–482
mode of transmission, 286 Menkes disease, 164
Measles, mumps, and rubella (MMR) vaccine, 19–20 Mental and behavioral health, 1039–1044
Meckel diverticulum, 787, 788 Menveo, 21, 22
Meconium aspiration syndrome (MAS), 949 Metabolic acidosis, 836–837
clinical presentation, 65 Metabolic alkalosis, 837, 838
diagnosis, 66 Metabolic disorders, 1036–1039
etiology, 65 amino acid metabolism disorder, 148–151
management, 66 body odors, 164–165
prevention, 66 carbohydrate metabolism disorder (see Carbohydrate metabolism
risk factors, 65 disorder)
Meconium ileus classifications, 143–145
cause, 72 familial hypercholesterolemia, 163
clinical presentation, 72 FAOD
diagnosis, 72 glutaric acidemia type II, 152
management, 73 MCAD, 152
Meconium peritonitis, 964 lysosomal storage disorders (see Lysosomal storage disorders)
Meconium plug syndrome Menkes disease, 164
clinical presentation, 72 newborn, clinical approach
common associated conditions, 72 general rules, 144–145
etiology, 72 hyperammonemia, 144
management, 72 initial laboratory evaluation, 143
Media, 889–890 management, 144
Medial collateral ligament injury (MCL), 482 pyridoxine (B6), 144
Medial epicondyle fracture, 497, 498 secondary tests, 144
Medical error, 921 newborn metabolic screening, 165
Medical neglect, 898 organic acidemia (see Organic acidemia)
Medical testimony, 911 peroxisomal disorders, 160–161
Medium-Chain Acyl-CoA dehydrogenase deficiency (MCAD), 152 porphyrias, 161–162
Medulloblastoma, 383, 384 pyrimidine metabolism, 163
Melanoma, 879 Smith–Lemli–Opitz syndrome, 163–164
Membranoproliferative glomerulonephritis (MPGN), 811 urea cycle disorders, 151
Membranous nephropathy (MN), 806, 807 Metachromatic leukodystrophy, 159–160
Menactra, 21, 22 Metatarsus adductus, 488
Mendellian syndromes Methanol ingestion, 229
achondroplasia, 131–132 Methemoglobinemia, 353, 701
Beckwith–Wiedemann Syndrome, 136–137 Methicillin-resistant Staphylococcus aureus (MRSA), 293
connective tissue dysplasias (see Connective tissue dysplasias) Methicillin-sensitive S. aureus (MSSA), 293
craniosynostosis syndromes, 130–131 Methylmalonic acidemia, 146
fragile X syndrome, 127–128 Microcephaly, 2, 566
Noonan syndrome, 128–129 Microcytic anemia
Sotos syndrome, 137–138 chronic disease, 350
Treacher Collins syndrome, 129–130 etiology, 350
Waardenburg syndrome, 129 laboratory test, 351
Ménétrier disease, 751 treatment, 351
Index 1163
iron deficiency anemia dystonic reactions, 578

blood transfusion, 350 Friedreich ataxia, 576
clinical presentation, 348, 349 Sydenham chorea, 578
dietary change, 349 tics, 577
etiology, 348 Tourette syndrome, 577, 578
laboratory test, 349 Mucocele, 631
oral iron therapy, 350 Mucopolysaccharidosis (MPS)
parenteral iron therapy, 350 type I, 156
lead poisoning, 353 type II, 156
methemoglobinemia, 353 type III, 156–157
sideroblastic anemia, 353 type IV, 157
thalassemias (see Alpha Thalassemia) Multicystic dysplastic kidney disease, 819
Microdeletion, chromosome disorders Multiple births
Alagille syndrome, 124–125 complications, 55
Angelman syndrome, 126–127 definition, 55
DiGeorge/Velocardiofacial syndrome, 125–126 dizygotic twins, 55
Prader–Willi Syndrome (PWS), 126 monozygotic twins, 55
WAGR syndrome, 124 Multiple sclerosis, 1009
Williams syndrome, 123–124 Mumps
22q11.2 Microdeletion syndrome, see DiGeorge syndrome clinical presentation, 286
Micropenis, 848 complications, 286
Microscopic polyangiitis (MPA), 544 diagnosis, 286
Middle ear effusion, 621 mode of transmission, 286
Migraine headache, 561 treatment, 286
Mild traumatic brain injury, 513–514 Munchausen syndrome by proxy, 900
Miliaria, 855–856 Murmurs, 50, 660, 661
Minerals Musculoskeletal radiology
calcium, 732 achondroplasia, 994
chloride, 732 acute osteomyelitis, 988
chromium, 732 aneurysmal bone cyst, 993
copper, 732, 733 apophyseal avulsion fracture, 996
fluoride, 733 Ewing sarcoma, 990
iodine, 733 fibromatosis colli, 995
iron, 733, 734 medial and lateral epicondyles, 996
magnesium, 734 non-accidental trauma with classic metaphyseal lesions and skull
potassium, 734 fracture, 986
selenium, 734 osteochondroma, 992
sodium, 734 osteogenesis imperfecta, 987
zinc, 734, 735 osteosarcoma, 991
Miserable malalignment syndrome, 519 rickets, 989
Mispositioned meatus, 52 Salter Harris II fracture, 985
Mixed connective tissue disease (MCTD), 537 supracondylar fracture, 995
Mixed hearing loss, 618, 619 Mushrooms ingestion, 229–230
Molluscum contagiosum, 510, 873–874 Myasthenia gravis, 571
Molluscum contagiosum conjunctivitis, 588 Mycobacterium avium-intracellulare
Monobactam, 932 causes, 325
Monozygotic twins, 55 clinical presentation, 325
Morquio syndrome, 157 treatment, 325
Mouth and oral cavity Mycobacterium tuberculosis, 268
ankyloglossia/tongue-tie, 47, 631 antituberculous medications
aphthous ulcers, 630 side effects, 324
bifid uvula, 630–631 BCG vaccine, 323
Bohn nodules, 47 challenges, 324, 325
cleft lip and palate, 47, 632–633 chest radiographs, 323, 324
cold panniculitis, 631 CNS disease, 322
dental trauma and avulsions, 634 etiology, 321
early childhood caries, 633–634 false-negative TST result, 323
Epstein pearls, 46, 47 false-positive TST result, 323
high arched palate, 47 follow-up, 325
macroglossia, 47 LTBI, 324
mucocele, 631 miliary tuberculosis, 322
natal teeth, 47 pleural TB, 322
odontogenic infection, 633 pulmonary disease, 321
parotitis, 631–632 risk factors, 321
Pierre Robin sequence, 47 skeletal tuberculosis, 322
Ranula, 47 superficial lymphadenopathy, 322
Robin sequence, 633 TB exposure, 324
Movement disorders treatment, 324
acute cerebellar ataxia, 575 whole blood interferon-gamma
ataxia telangiectasia, 575, 576 release assays, 323
1164 Index
Mycoplasma pneumonia diagnosis, 308

clinical presentation, 310, 311 prevention and indications, 309
incubation period, 310 symptoms, 308
testing for mycoplasma, 311 transmission rate, 308
Myelomeningocele, 569, 570 Neonatal alloimmune thrombocytopenia
Myocarditis, 681, 682 (NAIT), 372
Neonatal and infantile acne, 861–862
Neonatal gram-negative meningitis, 337
N Neonatal herpes simplex (HSV) infection, 337
Nail bed lacerations, 211 Neonatal hypoglycemia
Nail biting, 184 causes, 424
Nail-patella syndrome, 810, 811 diagnosis, 424, 425
Narcolepsy, 191 glucose value, 424
Nasal stuffiness, 46 Neonatal lupus erythematosus (NLE), 535
Nasal trauma, 624 Neonatal meningitis due to Listeria, 337
Nasolacrimal duct obstruction, 592 Neonatal seizures, 552
Necator americanus, 332 Neonatal sepsis
Neck clinical investigations, 67, 68
acute laryngitis, 638 clinical manifestation, 67
atlantoaxial subluxation, 472 clinical presentations, 67, 68
branchial cleft cyst, 637–638 early onset sepsis, 67
Castleman’s disease, 636 late onset sepsis, 67
cat scratch disease, 635 management, 68
cervical lymphadenitis, 634–635 medications, 68
chronic laryngitis/hoarseness, 639 risk factors, 67
infectious mononucleosis, 635 Neonatal streptococcal meningitis, 337
Kikuchi, 636 Neonatal testicular torsion, 849
Klippel–Feil syndrome, 472 Neonatal thyrotoxicosis, 432, 433
laryngomalacia, 640–641 Neonatology, 1022–1027
lymphadenitis, 636 Neoplastic disorders
lymphoma, 636–637 acute lymphoblastic leukemia
Sprengel deformity, 472 ataxia telangiectasia, 376
stridor, 639–640 Bloom syndrome, 376
thyroglossal cyst, 637 clinical presentation, 375
thyroid carcinoma, 638 diagnostic evaluation, 375
torticollis, 470–471 epidemiology, 375
tularemia, 636 Fanconi anemia, 377
vocal fold paralysis, 639 peripheral blood abnormalities, 375
Neck/cervical spine trauma, 209–210 treatment, 375
Necrotizing enterocolitis (NEC) trisomy 21, 376
causes, 73 acute myeloid leukemia
clinical presentation, 73 associated syndromes/risk factors, 377
indication for surgery, 74 diagnostic evaluation, 377
laboratory studies, 73 epidemiology, 377
management, 73 peripheral blood abnormalities, 377
mortality rates, 73 treatment, 377
Necrotizing fasciitis, 876 brain tumors (see Brain tumors)
aerobic and anaerobic flora, 300 chronic lymphocytic leukemia, 378
clinical presentation, 300 chronic myelogenous leukemia, 378
diagnosis, 300 germ cell tumors (see Germ cell tumors)
laboratory findings, 300 Hodgkin lymphoma
Negative predictive value (NPV), 916 diagnosis, 380
Neisseria gonorrhoeae, 586 incidence, 379
clinical presentation in males, 95 prognosis, 380
clinical presentation in females, 95 treatment, 380
DGI, 96, 307 Langerhans cell histiocytosis
diagnosis, 96 chemotherapeutic agents and side effects, 382
epididymitis, 307 clinical presentation, 381
gonococcal pharyngitis, 307 diagnosis, 381
gonococcal proctitis, 307 differential diagnosis, 381
gonococcal urethritis, 307 incidence, 381
incubation period, 307 prognosis, 382
neonatal conjunctivitis, 307 treatment, 381
screening, 308 lymphadenopathy
treatment, 96 biopsy criteria, 379
Neisseria meningitidis, 268 causes, 378
Index 1165
clinical approach, 378, 379 Sturge–Weber syndrome, 1001

mediastinal mass, 382 tethered cord with a terminal lipoma, 998
nephroblastoma (see Wilms tumor) thyroglossal duct cyst, 1012
neuroblastoma (see Neuroblastoma) tuberous sclerosis complex, 1002
non-Hodgkin lymphoma vein of Galen malformation, 1008
biopsy, 380, 381 Neutropenia
clinical presentation, 380 acute, 368
diagnosis, 380 benign familial neutropenia, 368
incidence, 380 congenital, 368 (see Congenital neutropenia)
prognosis, 381 cyclic
rhabdomyosarcoma laboratory test, 368
epidemiology, 387 ethnic, 368
treatment, 388 Nevus of Ito, 878
spinal cord compression, 382 Nevus of Ota, 878
superior vena cava syndrome, 382 Nevus Sebaceus (of Jadassohn), 856–857
tumor lysis syndrome, 382 Newborn bilirubin screening, 24
complications, 382 Newborn examination
laboratory test, 382 Apgar Score, 43
treatment, 382 newborn crying, 43
Nephroblastoma, see Wilms tumor temperature, 43
Nephrogenic diabetes insipidus (NDI), 816–817 Newborn metabolic screening, 165
Nephrology, 1115–1119 Newborn nursery care
Nephronophthisis (NPH), 818 critical congenital heart diseases screening, 39
Nephrotic syndrome, 804–806 24 hours discharge criteria, 40
Nerve gas agents, 230 eye prophylaxis, 39
Neuroblastoma, 386, 977 feeding, 39
clinical presentation, 385, 386 hearing loss, 39
diagnosis, 386 hepatitis B prophylaxis, 39
epidemiology, 385 hyperbilirubinemia, 40
treatment, 386 hypoglycemia, 39
Neurocutaneous disorders newborn screening, 39
neurofibromatosis type I, 559 umbilical cord care, 39
neurofibromatosis type II, 559 vitamin K 1 mg intramuscular injection, 39
Sturge–Weber syndrome, 560, 561 well-child visit, 40
tuberous sclerosis, 560 Niacin, 737
Neurofibromatosis type I, 384, 559 Nickel dermatitis, 860
Neurofibromatosis type II, 559, 560 Niemann–Pick disease (NPD), 158
Neurogenic shock, 257 Night terrors, 190
Neurology, 1087–1092 Nightmares, 190
Neuromuscular junction disorders, 571 Nocturnal enuresis, 822, 823
Neuropathies Nonaccidental burn injury, 896
Bell’s palsy, 574 Non-accidental trauma with classic metaphyseal lesions and skull
GBS, 572, 573 fracture, 986
HMSN, 573 Non-classic phenylketonuria, 149
Ramsay hunt syndrome, 574 Non-communicated hydrocephalus, 1003
Riley–day syndrome, 574 Non-gomerular hematuria, 801
SMA, 574 Non-Hodgkin lymphoma
tick paralysis, 575 biopsy, 380, 381
Neuroradiology clinical presentation, 380
acute left MCA territory infarction, 1007 diagnosis, 380
bilateral cervical and brachial plexus plexiform neurofibromas, incidence, 380
1000 prognosis, 381
coalescent mastoiditis, 1011 treatment, 380
craniopharyngioma, 1012 Noninvasive pregnancy testing (NIPT), 112
depressed skull fracture with traumatic subdural hemorrhages, Nonketotic hyperglycinemia, 150
1014 Nonnucleoside reverse transcriptase inhibitors (NNRTI), 936
global hypoxic ischemic injury, 1004 Non-polio virus
grade IV intraventricular hemorrhage, 997 clinical presentation
isolated sagittal craniosynostosis, 1013 acute hemorrhagic conjunctivitis, 282
juvenile pilocytic astrocytoma, 1006 congenital and neonatal infection, 282
left parietal calcified cephalohematoma, 1009 hand, foot and mouth disease, 282, 283
multiple sclerosis, 1009 herpangina, 282
non-communicated hydrocephalus, 1003 meningitis/encephalitis, 282
pituitary adenoma, 1007 myocarditis/pericarditis, 282
postseptal orbital cellulitis, 1010 diagnosis, 283
retropharyngeal abscess, 999 epidemiology, 282
skull fracture with an epidural hematoma, 1005 treatment, 284
1166 Index
Nonsteroidal anti-inflammatory drugs (NSAIDs), 530 Ophthalmia neonatorum

Nonstress test, 37 due to chlamydia, 586
Nontyphoidal Salmonellosis due to herpes simplex, 586
antibiotic therapy, 315 due to n. Gonorrhoeae, 585–586
clinical presentation, 315 Ophthalmology, 1092–1095
diagnosis, 315 Opiates ingestion, 227
incubation period, 314 Oppositional defiant disorder (ODD), 176
mode of transmission, 315 Optic neuritis, 597
Noonan syndrome, 671, 675, 782 Oral health screening, 27–28
DNA testing, 128 Oral thrush, 326
health supervision and preventive care, 128 clinical presentation, 326
major abnormalities, 128 incidence, 325
minor anomalies, 128 infection sources, 326
prevalence, 128 recurrence, 326
Normal bone marrow biopsy, 370, 371 risk of infection, 326
Normal renal function, 799 treatment, 326
Normocytic anemia Orbital cellulitis, 591
approach to, 359 Orbital fracture, 602
transient erythroblastopenia of childhood (see Transient Orbital rhabdomyosarcoma, 607
erythroblastopenia of childhood) Organic acidemia, 148
Norovirus, 281 biotinidase deficiency, 147
Nose glutaric aciduria type I/glutaric acidemia, 147–148
choanal atresia, 623 isolated beta-methylcrotonyl-CoA carboxylase deficiency, 147
epistaxis, 623 Isovaleric acidemia, 145
nasal trauma, 624 MSUD, 146
Nucleoside reverse transcriptase inhibitors (NRTI), 935–936 methylmalonic acidemia, 146
Null hypothesis, 918 propionic acidemia, 146–147
Nursemaid elbow (pulled elbow), 501–502 Organophosphate and carbamate insecticides, 230
Nutrition support, 1108, 1109 Ornithine transcarbamylase (OTC) deficiency, 151
enteral tube feeds, 749 Orthopedics, 1078–1083
nutrition assessment, 748 angular deformities
PN, 749, 750 blount disease (Tibia Vara), 485–486
supplements, 748, 749 genu valgum (knock-knee), 485
Nutritional disorders genu varum (bowleg), 484–485
FTT, 752 arthrogryposis, 466
milk protein allergy, 751, 752 back disorders
protein-losing enteropathy, 751 adolescent idiopathic scoliosis, 475–476
refeeding syndrome, 752, 753 back pain, 472–473
undernutrition, 750 Scheuermann kyphosis, 476, 477
vegetarian diets, 751 spondylolisthesis, 474
Nystagmus spondylolysis, 473–474
acquired nystagmus, 606 bone and joint infection/inflammation
clinical presentation, 606 acute hematogenous osteomyelitis, 469, 470
congenital sensory nystagmus, 606 diskitis, 470
management, 606 septic arthritis, 468–469
spasmus nutans, 606 transient synovitis, 468
vertebral body osteomyelitis, 470
bone tumors/tumors-like conditions
O aneurysmal bone cyst, 502, 503
Obesity, 511 Ewing sarcoma, 504, 505
Obsessive compulsive disorders (OCD), 181 osteochondroma, 503
Obstructive lesions, 662 osteoid osteoma, 503
Obstructive shock, 257 osteosarcoma, 504
Obstructive sleep apnea (OSA) syndrome, 724, 725 unicameral cyst, 502
clinical presentation, 629 foot disorders
definition, 629 calcaneovalgus foot, 489–490
diagnosis, 629, 630 cavus foot, 490
etiology, 629 clubfoot (talipes equinovarus), 489
treatment, 630 flat foot (pes planus), 490–491
Occult bacteremia, 310 ingrowing toenail, 493
Oculocutaneous tyrosinemia, 150–151 tarsal coalition, 491–492
Odds ratio (OR), 917 tip-toe walking, 492
Odontogenic infection, 633 fractures
Odor of sweaty feet, see Isovaleric acidemia ankle fractures, 499–501
Otitis media with effusion (OME), 615 clavicular fracture, 494
Oliguria/acute renal failure, 838 compartment syndrome, 500
Omphalocele, 50 humerus fracture, 495
Omphalomesenteric duct remnants, 51 lateral condyle fracture, 496–497
Onychomycosis, 865 medial epicondyle fracture, 497, 498
Index 1167
proximal humeral fracture, 494–495 Pancreatic insufficiency, 781, 782

radial head subluxation, 501–502 Pancytopenia
Salter–Harris Injuries, 493–494 differential diagnosis, 369
scaphoid fracture, 497–499 signs and symptoms, 370
supracondylar fracture of humerus, 495–496 treatment, 370
tibial shaft fracture, 499 Panic disorder, 180
toddler fracture, 499, 500 Papilledema, 595–597
hip disorders Papular urticaria, 866
developmental dysplasia of the hip, 477, 478 Papulosquamous disorders
Legg–Calve–Perthes Disease, 478–479 pityriasis rosea, 867
slipped capital femoral epiphysis, 479, 480 psoriasis, 866–867
intoeing Parainfluenza virus (PV)
femoral anteversion, 486–487 clinical manifestation, 280
internal tibial torsion, 487–488 epidemiology, 280
metatarsus adductus, 488 treatment, 280
knee pain and injuries Paraphimosis, 847
anterior cruciate ligament injury, 482 Parasitic conjunctivitis, 589
medial collateral ligament injury, 482 Parasomnias, 190
meniscal injury of the knee, 480–482 Parenteral nutrition (PN), 749, 750
osteochondritis dissecans, 483 Parinaud oculoglandular syndrome, 587
recurrent patellar dislocation/subluxation, 483, 484 Parotitis, 631–632
leg-length discrepancy, 466 Paroxysmal cold hemoglobinuria, 367, 368
limping child, 465, 466 Paroxysmal nocturnal hemoglobinuria (PNH)
neck disorders clinical presentation, 361
atlantoaxial subluxation, 472 etiology, 360, 361
Klippel–Feil syndrome, 472 laboratory tests, 361
Sprengel deformity, 472 treatment, 361
torticollis, 470–471 Partial aneuploidies, chromosome disorders
polydactyly of the hand, 467–468 Cri-du-Chat syndrome, 122
viral myositis, 468 De Grouchy syndrome, 123
Oseltamivir, 279 Wolf–Hirschhorn syndrome, 121–122
Osgood–Schlatter syndrome, 517, 518 Partial thickness burn, 215
Osmolality, 825 Parvovirus B19, 276
Osmotic cerebral edema, 252 incubation period, 276
Osmotic equilibrium, 825 mode of transmission, 276
Osseo-integrated auditory implant, 622 Pasteurella multocida
Osteochondritis dissecans, 483 clinical presentation, 311
Osteochondroma, 503, 992 risk, 311
Osteogenesis imperfecta, 136, 987 treatment, 311
abnormalities, 136 Patellofemoral pain, 518–519
health supervision and preventive care, 136 Patent ductus arteriosus (PDA), 665, 666
prevalence, 135 Patient safety and quality improvement, 924, 925, 1132–1134
type I, 135 Pearson marrow–pancreas syndrome, 356, 782
type II, 135 Pectus carinatum, 724
type III, 136 Pectus excavatum, 49, 723–724
type IV, 136 Pediatric acute respiratory distress syndrome (PARDS)
Osteoid osteoma, 503 anti-fungal and anti-viral therapy, 260
Osteosarcoma, 504, 991 cardiovascular complications, 259
Otalgia, 611 causes, 258
Otitis externa, 612 clinical investigations, 258
Otitis media with effusion (OME), 614–615 clinical presentation, 258
Ototoxicity, 621 definition, 258
Outpatient pneumonia, 295 gastrointestinal complications, 260
Ovarian cyst, 94 management, 259
Ovarian torsion, 93 pericardial tamponade, 260
Over-the-counter medications, 939 positive pressure ventilation, 259
renal complications, 260
Pediatric Advanced Life Support (PALS), 624
P Pediatric audiometric testing
Pain management ABR, 620
in neonates, 943 BOA, 620
in older children, 943–944 conventional audiometry, 620
Pain syndromes evoked otoacoustic emission, 620
AMPS, 542, 543 hearing loss classification, 620
BJHS, 542 play audiometry, 620
growing pains, 541, 542 tympanometry, 620, 621
Painful erythematous eye, 585 VRA, 620
Palivizumab, 280 Pediatric autoimmune neuropsychiatric disorders associated with
Pallor, 43 Streptococcus infections (PANDAS), 299
1168 Index
Pediatric metabolic syndrome, 462 Peptic ulcer diseases

Pediatric pharmacology duodenitis, 772
absorption, 927 gastritis and peptic ulcers, 771–772
antibiotics ZES, 772
adverse reactions, 934 Performance-enhancing drugs, 521
aminoglycosides, 930 Perianal bacterial dermatitis, 298
amoxicillin-clavulanate, 931 clinical presentation, 298
ampicillin, 930–931 diagnosis, 298
anti-pseudomonal penicillins, 931 incidence, 298
beta lactam antibiotics, 930 treatment, 298
carbapenems, 932 Perianal streptococcal dermatitis, see Perianal bacterial dermatitis
cephalosporins (penicillinase-resistant), 931–932 Pericardial tamponade
clindamycin, 932 causes, 260
fluoroquinolones, 933 complications, 260
macrolides, 932–933 definition, 260
monobactam, 932 diagnosis, 260
penicillinase-resistant penicillins, 930, 931 management, 260
rifampin, 933 signs and symptoms, 260
tetracycline, 933 Periodic fever syndromes, 539
trimethoprim/sulfamethoxazole, 933 Perioral irritant contact dermatitis, 859
vancomycin, 934–935 Periorbital cellulitis, 310
antiemetics, 941 Periorbital tumor, 606–607
antifungals, 937–938 Periorificial dermatitis, 862
antiparasitics, 936–937 Peripheral pulmonary stenosis (PPS), 671
anti-ulcers, 940–941 Peritoneal irritation, 248
antivirals Peritonsillar abscess (PTA), 627
acyclovir, 935 Permissive hypercapnia, 263
antihypertensive medications, 939–940 Peroxisomal disorders, 161
foscarnet, 935 X-ALD, 160–161
ganciclovir (IV), 935 Zellweger syndrome, 160
nonnucleoside reverse transcriptase inhibitors, 936 Persistent hematuria/proteinuria
nucleoside reverse transcriptase Inhibitors, 935–936 acute postinfectious glomerulonephritis, 808, 809
other agents, 935 alport syndrome, 810
protease inhibitors, 936 anti-glomerular basement disease, 812, 813
valacyclovir, 935 congenital nephrotic syndrome, 807
valganciclovir, 935 dense deposit disease, 811
bioavailability, 927 familial thin basement membrane nephropathy, 813
diuretics, 938–939 Frasier syndrome, 808
drug reactions, 930 good pasture syndrome, 813
drug-drug interactions, 928 IgA nephropathy, 809, 810
FDA adverse event reporting system, 930 infantile nephrotic syndrome, 807, 808
half-life (t½), 929 lupus nephritis, 812
hepatic metabolism, 927–928 MN, 806, 807
over-the-counter medications, 939 MPGN, 811
pain management nail-patella syndrome, 810, 811
in neonates, 943 nephrotic syndrome, 804–806
in older children, 943–944 Persistent pulmonary hypertension of newborn (PPHN)
prescribing medications, 929–930 antidepressants, 64
renal elimination, 928, 929 clinical presentation, 65
sedation definition, 64
deep, 941 diagnosis, 65
general, 941–942 etiology, 64
minimal, 941 genetic factors, 64
moderate, 941 management, 65
preprocedural evaluation, 943 Petechiae, 44
procedural, 942 Peutz–Jeghers syndrome (P-JS), 788–789
protocol, 942 Pfeiffer syndrome, 130
reversal agents, 942 PHACE syndrome, 673
Pediculosis, 99, 865 Phagocyte function
Pelvic inflammatory disease (PID) Chediak–Higashi syndrome
causes, 97 CHS1/LYST gene, 407
clinical diagnostic criteria, 97 clinical presentation, 407
diagnosis, 97 risk of malignancy, 407
genital tract infection, 97 treatment, 407
treatment, 98 chronic granulomatous disease
ultrasonography, 98 clinical presentation, 406
Pendred syndrome, 619 diagnosis, 406
Penicillinase-resistant penicillins, 930, 931 treatment, 407
Index 1169
leukocyte adhesion defect Pneumocystis jiroveci

Pharmacology and pain management, 1134–1135 treatment, 330
Pharyngoconjunctival fever, 587 Pneumocystis pneumonia, 330
Phenothiazines, 227–228 Pneumomediastinum, 722, 723
Phenylketonuria (PKU), 148 Pneumonia, 310, 714–716
clinical manifestations, 148 Pneumothorax and pneumomediastinum, 722
clinical presentation, 148 chest radiograph, 66
dietary treatment, 148 management, 66
imaging studies, 148 risk factors, 66
pharmacologic management, 148 Point of maximal cardiac impulse (PMI), 49
Pheochromocytoma, 451 Poisoning and toxic exposure
Phimosis, 847 evaluation, 222
Phonological speech disorders, 169 general measures, 222
Physical fitness, 521 prevention, 222
Physical neglect, 898 Poland sequence, 138–139
Physiologic jaundice Poliomyelitis
causes, 58 clinical presentation, 284
diagnosis, 57 epidemiology, 284
risk factors, 58 treatment, 284
TSB concentrations, 57 Polyarthropathy syndrome, 277
Pierre Robin sequence, 139 Polycystic ovarian syndrome (PCOS), 92, 451, 452
Pilocytic astrocytoma, 383 Polycythemia vera, 56, 374, 375
Pineoblastoma, 384 Polydactyly of the hand, 53, 467–468
Pinworm, 331, 332 Polymicrogyria, 565
Pituitary adenoma, 1007 Polymyositis, 538
Pituitary gland disorder Polythelia, 49
cerebral salt wasting, 427 Pompe disease, 154
congenital hypopituitarism (see Congenital hypopituitarism) Porphyria cutanea tarda, 162
craniopharyngioma, 425, 426 Porphyrias
DI (see Diabetes insipidus (DI)) acute intermittent porphyria, 161–162
growth hormone erythropoietic protoporphyria, 162–163
adverse effects, 422 porphyria cutanea tarda, 162
biologic effects, 422 Portal hypertension, 797
definition, 422 Portal venous gas, 962
discontinuing treatment, 422 Positive predictive value (PPV), 916
IGF-1, 422 Post inflammatory hypo/ hyper-pigmentation, 877
indications, 422 Posterior fontanelle, 44
therapy, 422, 423 Posterior plagiocephaly, 130
hyperpituitarism (see Hyperpituitarism) Posterior urethral valves (PUV), 845, 978
neonatal hypoglycemia (see Neonatal hypoglycemia) Postnatal rubella, 287
SIADH (see Syndrome of inappropriate ADH secretion (SIADH)) Postseptal orbital cellulitis, 1010
Pityriasis alba, 876–877 Post-streptococcal reactive arthritis (PSRA), 531
Pityriasis rosea, 867 Post-term birth, 35
Placenta accreta, 37 Post-traumatic/post-concussion headaches, 563
Placenta increta, 37 Post-traumatic stress disorders (PTSD), 182
Placenta percreta, 37 Potassium (K), 734
Placental abruption, 37 hyperkalemia, 834, 835
Plagiocephaly, 3 hypokalemia, 835
causes, 3 Prader–Willi syndrome (PWS)
craniosynostosis, 3–4 FISH/microarray analysis, 126
deformational plagiocephaly, 3, 4 health supervision and preventive care, 126
diagnosis, 3 high-resolution chromosome analysis, 126
treatment, 3 major abnormalities, 126
Plasmodium, 331 minor anomalies, 126, 127
Plasmodium falciparum, 331 prevalence, 126
Platelet disorders Preauricular pits/sinus (PPS), 611
approach to, 371 Precocious puberty (PP), 443
thrombocytopenia, 371 (see Thrombocytopenia) clinical presentation, 445
Plethora, 44 definition, 443
Pleural effusion, 721, 722 diagnosis, 445
Pneumatosis intestinalis, 962 gonadotropin-dependent PP, 444, 445
Pneumococcal infection, 294, 295 gonadotropin-independent PP, 444, 445
Pneumococcal meningitis, 295 pubertal signs, 443
Pneumococcal vaccines, 17–18 treatment, 445
1170 Index
Preconception screening, 112 Primary intestinal lymphangiectasia, 782

Preeclampsia, 41–42 Primary muscular diseases
Preimplantation genetic diagnosis (PGD), 112 Becker muscular dystrophy, 572
Premature adrenarche, 441, 442 congenital myotonic dystrophy, 572
Premature atrial contractions (PACs), 652, 653 Duchenne muscular dystrophy, 572
Premature infants, 747, 748 Primary syphilis, 320
Premature menarche, 443 Primary tooth avulsion, 634
Premature rupture of membranes (PROM) Primitive neuroectodermal tumor (PNET), 384
clinical history, 40 Primitive reflexes, 581
expectant management, 40 Procedure bias, 913
indications for delivery, 41 Prolactinoma, 428
management, 40 Prolonged QT interval, 656
medications, 41 Propionic acidemia, 146–147
risks, 40 Protease inhibitors, 936
Premature ventricular contractions (PVC), 656 Protein, 741
Prenatal care Protein-losing enteropathy, 751
abnormal alpha-fetoprotein, 37 Proteinuria, 799, 800
C-section, indications, 37 Proton pump inhibitors (PPIs), 940–941
fetal distress, 37 Protozoa
general neonatal risks, 36 cryptosporidiosis
placenta, 37 clinical presentation, 329
prematurity risk, 36 mode of transmission, 329
preterm high mortality rate, 36 treatment, 330
routine prenatal laboratory tests, 35, 36 Entamoeba histolytica
umbilical cord, 36 clinical presentation, 329
Prenatal diagnosis, 112–113 diagnosis, 329
Pre-Patellar Bursitis, 519 mode of transmission, 329
Preseptal cellulitis, 590–591 treatment, 329
Preterm birth, 35 giardiasis
Prevention of infectious diseases clinical presentation, 329
antimicrobial resistance, 269 diagnosis, 329
breastfeeding, 268, 269 mode of transmission, 329
child-care centers, 267 treatment, 329
hospital and office, 268 plasmodium (see Malaria)
immunocompromised hosts Toxoplasma gondii
asplenia, 270 clinical presentation, 330
brain injury, 270 diagnosis, 330
central nervous system, 269 mode of transmission, 330
indwelling central lines, 270 Pneumocystis jiroveci
malignancy, 270 clinical presentation, 330
malnutrition, 269 diagnosis, 330
recreational water use, 269 mode of transmission, 330
vector-borne disease prevention, 269 treatment, 330
Preventive medicine Proximal humeral fracture, 494–495
autism screening, 25 Proximal RTA type II, 814
blood pressure screening, 24 Prune belly syndrome, 51
depression screening, 27 Pseudohypoparathyroidism (PHP), 437
developmental screening, 25 Pseudomonas species
hearing screening, 25 antimicrobial therapy, 314
HIV screening, 26–27 causes, 314
iron deficiency anemia screening, 26 clinical presentation, 314
lead screening, 25, 26 risk factors, 314
newborn bilirubin screening, 23, 24 Pseudostrabismus, 604–605
oral health screening, 27–28 Psoriasis, 866–867
tobacco, alcohol, and substance use, 27 Psychosocial dwarfism, 421
TB screening, 27 Psychosocial issues and child abuse, 1125–1128
UA screening, 26 Psychosomatic disorders
vision screening, 24 clinical presentation, 189
Primary adrenal insufficiency, 449 differential diagnosis, 189
Primary amenorrhea, 91 management, 189
Primary ciliary dyskinesia, 720, 721 screening and rating scales, 189
Primary craniosynostosis, 3 symptoms, 189
Primary headache syndromes Ptosis
diagnosis, 562 acquired, 593
treatment of, 562, 563 congenital, 593
Primary hypersomnia, 191 Puberty disorder
Primary hypogonadism, 446 delayed puberty, 446
Primary immunodeficiencies, 405–406 gynecomastia, 447
Primary insomnia, 191 isolated premature thelarche, 442, 443
Index 1171
Klinefelter syndrome, 447 laboratory test, 347

McCune–Albright syndrome, 445, 446 pathogenesis, 347
PP (see Precocious puberty (PP)) Rh sensitization prevention, 347
premature adrenarche, 441, 442 treatment, 347
premature menarche, 443 Red reflex examination, 46
primary hypogonadism, 446 Reed–Sternberg cell, 379
Turner syndrome, 448 Refeeding syndrome, 752, 753
Pulmonary function testing (PFT), 691 Referred abdominal pain, 760, 761
Pulmonary hypertension, 724 Reflux esophagitis, 771
Pulmonary interstitial emphysema, 948 Refraction disorders
Pulmonary sequestration, 704 contact lens-related problems, 606
Pulmonary thromboembolism, 959 nystagmus, 606
Pulmonary valve stenosis (PS), 670, 671 referral criteria, 606
Pulmonary vascular resistance (PVR), 658 types, 605
Pulmonology, 1104–1108 uncorrected refractive error, 605
Pulse oximetry, 692 Regional lymphadenopathy, 313
Prune-Belly syndrome, 845–846 Reiter syndrome, 306
Pygmalion effect bias, 913 Renal disease, 754
Pyogenic arthritis, 310, 468 Renal failure
Pyruvate kinase deficiency AIN, 820, 821
clinical presentation, 365 AKI, 819–820
deficiency, 364 ATN, 821
laboratory, 365 HUS, 821, 822
treatment, 365 Renal tubular acidosis (RTA), 813, 814
Renal vein thrombosis (RVT), 823
Renin–Angiotensin–aldosterone system, 836
Q Reporting medical error, 923, 924
Quality improvement (QI), 924 Research and statistics, 1131–1132
Quinsy tonsillectomy, 627 Respiratory conditions
acute bronchiolitis, 707, 708
ALTE and BRUE, 725, 726
R asthma
Rabies virus acute asthma exacerbations, 714
clinical presentation, 288 assessment, 710, 711
mode of transmission, 288 beta-2 agonists, 713
passive and active immunization, 288 classification, 711
treatment, 288 differential diagnosis for, 710
Radioallergosorbent (RAST) testing, 403 EIA, 711, 712
Radionuclide cystography, 843 inhaled corticosteroids, 713
Ramsay hunt syndrome, 574 initial controller therapy, 713
Ranula, 47 leukotriene receptor antagonists, 714
Rasmussen encephalitis, 555 management of, 712
Rathke pouch, 421 pathophysiology, 710
Reactive arthritis, 532 symptoms and natural course, 709, 710
Reactive attachment disorder, 182 BPD, 708, 709
Reading disorders, 170 bronchiectasis, 716, 717
Recall bias, 913 cystic fibrosis
Rectal prolapse, 777 clinical presentation, 717, 718
Recurrent acute otitis media, 614 complications, 718–720
Recurrent pancreatitis, 763–764 diagnosis, 719
Recurrent patellar dislocation/subluxation, dysfunction/absence, 717
483, 484 management, 719, 720
Red blood cell (RBC) disorders primary ciliary dyskinesia, 720, 721
ABO incompatibility therapies for treatment, 720
classification markers, 348 diagnostic testing for
clinical approach to child with blood gas analysis, 693
anemia, 348 carbon monoxide gas, 692
clinical presentation, 347 CBG, limitations of, 693
diagnosis, 348 chest imaging, 694
prevalence, 347 lung volumes, 692
treatment, 348 PET, 691
anemia pulse oximetry, 692
in newborn, 345, 346 spirometry, 691
prevalence, 345, 346 extrapulmonary respiratory conditions
macrocytic anemia (see Macrocytic anemia) pectus carinatum, 724
microcytic anemia (see Microcytic anemia) pleural effusion, 721, 722
RH incompatibility pneumomediastinum, 722, 723
antenatal diagnosis, 347 pneumothorax, 722
clinical presentation, 347 scoliosis, 724
1172 Index
Respiratory conditions (cont.) Retinoblastoma (RB), 595, 596

FB aspiration, 706 Retinopathy of prematurity (ROP), 599, 600
lower airway and parenchyma causes, 598, 599
bronchogenic cyst, 704 complication, 599
congenital lobar emphysema, 705, 706 definition, 598
congenital pulmonary adenomatoid malformation, 705 early treatment, 600
pulmonary sequestration, 704 initial retinal screening, 599
tracheal stenosis, 705 management, 599
vascular ring/sling, 705 risk factors, 599
OSA, 724, 725 screening descriptions, 599
pneumonia, 714–716 treatment programs, 600
pulmonary hypertension, 724 Retropharyngeal abscess, 627–628, 999
SIDS, 726 Rett syndrome, 581
signs and symptoms RH incompatibility
acute stridor, differential diagnosis of, 694, 695 antenatal diagnosis, 347
apnea, 699, 700 clinical presentation, 347
chronic hypoxia, 700 laboratory test, 347
chronic stridor, differential diagnosis of (see Chronic stridor, pathogenesis, 347
differential diagnosis) Rh sensitization prevention, 347
cough, 697, 698 treatment, 347
cyanosis, 700 Rhabdomyosarcoma
exercise intolerance, 699 of the bladder, 983
hemoptysis, 701, 702 clinical presentation, 387
hypertrophic pulmonary osteodystrophy, 701 epidemiology, 387
methemoglobinemia, 701 treatment, 388
respiratory failure, 699 Rheumatology, 1085–1087
stridor/wheezing, 694 Rhinoviruses
tachypnea, 698 clinical features, 281
thoracic deformities, pectus excavatum, 723–724 epidemiology, 280, 281
pulmonary hemosiderosis, 706, 707 testing, 281
upper airway Rhus dermatitis (Poison Ivy), 859
bacterial tracheitis, 703, 704 Rhythm strips, 650
epiglottitis, 703 Riboflavin, 737
viral croup, 702, 703 Rickets, 989
Respiratory distress syndrome (RDS), 49, 947 clinical presentation, 440
anatomy of pediatric airway, 197–200 hypophosphatemic rickets, 441
cause, 62, 198 vitamin D deficiency (see Vitamin D deficiency rickets)
clinical presentation, 63 Rickettsia rickettsii, 318
definition, 197 Rifampin, 933
diagnosis, 63 Rifampin antibiotic prophylaxis, 310
differential diagnosis, 199, 200 Right ovarian torsion, 982
etiology, 198 Riley-day syndrome, 574
incidence and severity, 62 Ritter disease, see Staphylococcal scalded skin
initial emergency care syndrome (SSSS)
airway management, 200 RNA virus
breathing management, 200 HIV (see Human Immunodeficiency virus (HIV))
oxygenation and ventilation, 200, 201 measles (see Measles virus)
lower airway infection, 199 mumps (see Mumps)
lower airway obstruction, 199 non-polio virus
management, 63 acute hemorrhagic conjunctivitis, 282
mediastinal masses, 199 congenital and neonatal infection, 283
pericardial tamponade, 199 diagnosis, 283
pleural effusion, 199 epidemiology, 282
pneumothorax/tension pneumothorax, 199 hand, foot and mouth disease, 282, 283
prenatal steroids, 64 herpangina, 282
risk factors, 62 meningitis/encephalitis, 282
surfactant, 62 myocarditis/pericarditis, 282
surfactant protein deficiency, 62 treatment, 284
upper airway infection, 199 poliomyelitis
upper airway obstruction, 198 clinical presentation, 284
See also aka Hyaline Membrane Disease diagnosis, 284
Respiratory failure, 197 epidemiology, 284
Respiratory syncytial virus (RSV), 280 treatment, 284
Restless leg syndrome, 191 rabies virus (see Rabies virus)
Restrictive cardiomyopathy, 684, 685 rubella virus (see Rubella virus)
Reticulocyte count, 348 Robin sequence (RS), 633
Retinal detachment, 601 Rocky mountain spotted fever (RMSF)
Retinal hemorrhage, 208, 597–598 clinical presentation, 318, 319
Retinitis pigmentosa (RP), 597 complications, 319
Index 1173
vs. ehrlichiosis, 319 minimal, 941

epidemiology, 318 moderate, 941
laboratory testing, 319 procedural, 942
treatment, 319 protocol, 942
Root cause analysis (RCA) process, 922 reversal agents, 942
Roseola infantum, 276 Seizures and epilepsy
Rotavirus anti-epileptic drugs, side effects of, 556
clinical presentation, 281 BECTS, 553, 554
diagnosis, 282 childhood absence epilepsy, 552, 553
epidemiology, 281 classification of, 551
Rotavirus vaccine, 16, 1018 epilepsy mimics, 558, 559
Round pneumonia, 956 febrile seizures, 551, 552
Routine prenatal laboratory tests, 35, 36 infantile spasms, 552
Rubella virus juvenile myoclonic epilepsy, 554
clinical presentation Landau–Kleffner syndrome, 554, 555
congenital rubella syndrome, 287 Lennox–Gastaut syndrome, 554
postnatal rubella, 287 neonatal seizures, 552
epidemiology, 287 Rasmussen encephalitis, 555
Rumack-Matthew nomogram, 225 SE, 556–558
Rumination, 769 type, 556
Selection bias, 913
Selective IgA deficiency (sIgAD)
S clinical presentation, 409
S. aureus food poisoning, 292 diagnosis, 409
S. pneumoniae, 338 treatment, 409
epidemiology, 294 Selective mutism, 180
risks, 294 Selective serotonin reuptake inhibitors (SSRIs), 64
Sacral dimple, 53 Selenium, 734
Saethre-Chotzen syndrome, 130 Sensorineural hearing loss (SNHL), 618
Salicylic acid ingestion, 225–226 Sentinel event, 922
Salmonella infection, 267 Separation anxiety disorder, 180, 889
Salter–Harris Injuries, 493–494, 985 Septic arthritis, 468–469
Sanfilippo syndrome, 156–157 Septic shock, 240, 255–257
Sapovirus, 281 Septo-optic dysplasia, 424
Sarcoidosis, 540, 541 Serogroup B meningococcal vaccines, 22
Scabies, 99, 865 Serum sickness
Scaphocephaly, 130 causes, 401
Scaphoid fracture, 497–499 clinical presentation, 401
Scarlet fever (scarlatina), 297 treatment, 401
causes, 296 Sever’s disease, 520
clinical presentation, 296, 297 Severe combined immunodeficiency (SCID)
streptococcosis, 297 clinical presentation, 412
treatment, 297 complications, 412
Scheuermann kyphosis, 476, 477 diagnosis, 412
Schistosoma haematobium, 333 treatment, 412
Schistosoma japonicum, 333 Sex chromosome aneuploidies,
Schistosoma mansoni, 333 chromosome disorders
Schistosomiasis, 333 Klinefelter syndrome, 118–119
School refusal, 889 Turner syndrome, 119–121
Schwachman–Diamond syndrome (SDS), 781 XYY syndrome, 119, 121
clinical presentation, 358 Sexual abuse
complications, 358 clinical investigations, 899
genetics, 358 examination, 899
laboratory findings, 358 incidence, 898
treatment, 358 legal issues, 899
Scoliosis, 474–475, 724 management, 900
Scorpion stings, 215 medical history-taking, 898
Scrotal masses, 94 Sexual behaviors
Seborrheic dermatitis, 860 gender identity disorder, 192
Secondary amenorrhea, 91 homosexuality, 192
Secondary/central adrenal insufficiency, 450 masturbation, 191–192
Secondary craniosynostosis, 3 sexual abuse, 191
Secondary syphilis, 320 sexual identity development, 192
Sedation Sexual identity development, 192
deep, 941 Sexual maturity ratings (SMRs)
general, 941–942 in boys, 443, 444
intraprocedural monitoring, 943 in girls, 443, 444
1174 Index
Sexually transmitted disease (STDs) in adolescents, 192 treatment, 363

Chlamydia trachomatis, 97 Sickle cell nephropathy, 823
herpes simplex, 99 Sideroblastic anemia, 353
HIV, 99 Sinding–Larsen–Johannsen disease, 518
HPV, 98 Single hamartomatous polyp, 788
Neisseria gonorrhoeae, 95–97 Single umbilical artery (SUA), 51
pediculosis, 99 Sinus arrhythmia, 646, 652
pelvic inflammatory disease, 97, 98 Sinuses
scabies, 99 acute rhinosinusitis, 624–625
trichomoniasis, 98 chronic sinusitis, 625
vaccination, 99 frontal sinus trauma, 626
Shigella, 267 Sjögren syndrome, 537
child care center, 316 Skin diseases, 510
clinical presentation, 316 Skin disorders of the newborn
complications, 316 diaper dermatitis, 857
diagnosis, 316 erythema toxicum, 855, 856
incubation period, 316 miliaria, 855–856
mode of transmission, 316 nevus Sebaceus (of Jadassohn), 856–857
treatment, 316 transient neonatal pustular melanosis, 855
Shock Skull fractures, 45, 1005
anaphylactic shock, 257 Sleep disorders
cardiogenic shock, 255 bedtime refusal/frequent awakening, 190–191
common features, 253 benign sleep myoclonus of infancy, 191
compensated stage, 253 classifications, 189–190
decompensated stage, 254 dyssomnias, 191
definition, 253 night terrors, 190
distributive shock/septic shock, 255–257 nightmares, 190
hypovolemic shock, 254–255 NREM sleep, 189
management strategies, 254 parasomnias, 190
neurogenic shock, 257 parental education, 189
obstructive shock, 257 REM sleep, 189
Short bowel syndrome, 782 sleep needs according to age, 189
Short stature, 420, 422 Sleep-disordered breathing (SDB), 629
Shwachman-Diamond syndrome, 752 Slipped capital femoral epiphysis (SCFE), 479, 480
Sibling rivalry, 889 Small bowel obstruction, 975
Sick sinus syndrome (SSS), 655 Small for gestational age (SGA), 35
Sickle cell disease Smith–Lemli–Opitz syndrome, 163–164
acute chest syndrome Snake bites
clinical presentation, 362 characteristics of poisonous snakes, 213
etiology, 362 clinical evaluation, 214
treatment, 362 clinical presentation, 213, 214
aplastic crisis management, 214
clinical presentation, 363 Snuffles (rhinorrhea), 46
etiology, 363 Social communication disorder, 169–170
laboratory test, 363 Social phobia, 180
treatment, 363 Sodium (Na), 734
clinical presentation, 361 hypernatremia, 827–829
complications, 361 hyponatremia, 829–831
dactylitis, 363 water intoxication, 831
fever, 362 Sodium diarrhea, 785
hydroxyurea, 362 Solid foods
infection, 362 adolescents, 747
laboratory test, 361, 362 children, 746
neurologic complications home-prepared baby foods, 746
clinical presentation, 364 toddlers, 746
imaging, 364 Solitary cyst, 91
incidence, 364 Solitary kidney, 511
primary prevention of stroke, 364 Solitary thyroid nodules, 433
secondary prevention of stroke, 364 Sotos syndrome, 137–138
treatment, 364 Sound amplification devices, 622
priapism, 363 Southern tick associated rash illness (STARI), 319
renal disease, 364 Spasmus nutans, 606
splenic sequestration, 363 Spastic diplegia, 580
clinical presentation, 363 Spastic hemiplegia, 579, 580
prognosis, 363 Spastic quadriplegia, 580
treatment, 363 Spina bifida occulta, 569
and trait, 511 Spinal cord diseases
vaso-occlusive crisis atlantoaxial instability, 570, 571
prevention, 363 meningocele, 569
risk factors, 362 myelomeningocele, 569, 570
Index 1175
spina bifida occulta, 569 Staphylococcal scalded skin syndrome (SSSS), 875
spinal cord trauma, 570 clinical presentation, 292
spinal epidural abscess, 570 diagnosis, 292
tethered cord, 569 treatment, 292
transverse myelitis, 570 Staphylococcus aureus, 268
Spinal cord trauma, 570 Staphylococcus epidermidis, 292
Spinal epidural abscess, 570 Staphylococcus saprophyticus, 292
Spinal muscular atrophy (SMA), 574 Statistical hypothesis, 918–919
Spirometry, 691 alternative hypothesis, 918
Spleen, 50 confidence interval, 919
Splenic rupture, 249 intention-to-treat analysis, 919
Splenic sequestration null hypothesis, 918
clinical presentation, 363 P value, 919
prognosis, 363 power of a study, 918
treatment, 363 standard deviation, 919
Splenomegaly, 272 type I error, 918
Spondylolisthesis, 474 type II error, 918
Spondylolysis, 473–474 Status epilepticus (SE), 556–558
Sporothrix schenckii, 328 anticipatory medication, 219
Sports medicine, 1083–1085 anticonvulsant medication, 218, 219
AC dislocation, 515–516 causes and risk factors, 217, 218
ankle sprain, 517 definitions, 217
anterior shoulder (glenohumeral) dislocation, 515 laboratory studies, 218
deep hematoma of thigh, 516–517 management, 218
female athlete triad, 520–521 Stevens–Johnson syndrome (SJS), 870, 872–873
hydration and rehydration, 520 Stickler syndrome, 619
injury prevention, 512, 513 Strabismus, 46
Little Leaguer’s elbow, 516 amblyopia, 605
Little Leaguer’s shoulder, 516 definition, 603
mild traumatic brain injury, 513–514 esotropia, 603, 604
Osgood–Schlatter syndrome, 517, 518 exotropia, 603, 604
patellofemoral pain, 518–519 hypertropia, 603
performance-enhancing drugs, 521 hypotropia, 603
physical fitness, 521 pseudostrabismus, 604–605
pre-participation evaluation vertical misalignment, 604
cardiac conditions, 509 Streptococcal pharyngitis, 295
cerebral palsy, 510 Streptococcal toxic shock syndrome, 299
chest pain, 508 clinical presentation, 299
clearance, 507 diagnosis, 299
clinical background, 507 risk factors, 299
diabetes mellitus, 509 treatment, 299
Down syndrome, 510 Streptococcus agalactiae, see Group B
eating disorders, 511 streptococcal (GBS) infection
exercise-induced bronchoconstriction, 509 Streptococcus pneumoniae, 294
eyes, 510 Streptococcus pyogenes, 275, 295
fever, 508 Stridor, 639–640
furuncle/carbuncles/folliculitis/impetigo/cellulitis, 510 Stroke, 568
heart murmur, 509 Strongyloides stercoralis, 333
heat illness, 511 Strongyloidiasis, 333
herpes simplex, 510 Study designs
HIV infection, 509 anecdotal evidence, 915
molluscum contagiosum, 510 case reports, 914
obesity, 511 case series, 914
objective, 507 case studies, 914
physical examination, 507 case-control studies, 914
screening tests, 507 cohort studies, 914
seizure disorder, poorly-controlled, 509 cross-sectional studies, 914
seizure disorder, well-controlled, 509 descriptive epidemiologic studies, 915
sickle cell disease and trait, 511 meta-analyses, 914
skin diseases, 510 randomized controlled trials, 913
solitary kidney, 511 statistically significant vs. clinically significant studies, 915
syncope, 508 systematic reviews, 914
tinea corporis, 510 Sturge–Weber syndrome, 560, 561, 594, 1001
pre-patellar bursitis, 519 Stye, 591–592
Sever’s disease, 520 Subacute (de Quervain) thyroiditis, 431
Sinding–Larsen–Johannsen disease, 518 Subarachnoid bleed, 208
Sprengel deformity, 472 Subconjunctival hemorrhage, 46
Standard error of mean (SEM), 919 Subcutaneous fat necrosis of the newborn (SCFN), 44
Staphylococcal, coagulase-negative, 293 Subdural hematoma, 207–208
Staphylococcal infections, 290 Subgaleal hemorrhage, 45
1176 Index
Subglottic hemangioma, 697 Tetracycline, 933

Subglottic stenosis (SGS), 696 Tetraiodothyronine (T4), 429
Substance abuse, 193 Tetralogy of Fallot, 953
alcohol, 87 Thalassemias
amphetamines, 87 alpha (see Alpha Thalassemia)
anabolic steroids, 88 beta (see Beta Thalassemia)
cocaine, 87 Thiamin, 737
drug/alcohol abuse, 85 Throat and oropharynx
drug testing, 88 adenoidectomy, 628–629
hallucinogens, 87 OSA syndrome (see Obstructive sleep apnea (OSA) syndrome)
indications, 88 peritonsillar abscess, 627
inhalants, 88 retropharyngeal abscess, 627–628
marijuana, 87 tonsillitis/pharyngitis, 626–627
opioids, 87 Throat cultures diagnostic standard, 626
over-the counter medications, 88 Thrombocytopenia
prescription medicine, 88 amegakaryocytic thrombocytopenia, 372
red flags, 88 Bernard Soulier syndrome, 373
screening, 85, 86 diagnosis, 371
tobacco, 86 Glanzmann thrombasthenia, 373
Sudden infant death syndrome (SIDS), 726 hemolytic uremic syndrome, 372
Suicidal behaviors immune thrombocytopenic purpura, 372
attempting suicide, risk factors, 187 Kasabach–Merritt syndrome, 371
completed suicide, risk factors, 187 marrow suppression, 372
management, 188 neonatal thrombocytopenia, 372
prevention, 188 thrombocytopenia absent radii syndrome, 373
prognosis, 188 thrombotic thrombocytopenic purpura, 372
screening and assessment, 187 Wiskott Aldrich syndrome, 373
Superficial burn, 215 Thrombotic thrombocytopenic purpura, 372
Superior mesenteric artery syndrome, 773 Thumb polydactyly, 467
Supervisory neglect, 898 Thumb sucking, 183, 184
Supportive home therapy, 216, 217 Thyroglossal cyst, 637, 1012
Supracondylar fracture of humerus, 495–496 Thyroid cancer, 433
Supraventricular tachycardia (SVT), 647, 653–655 Thyroid carcinoma, 638
Surfactant deficiency disease, 947 Thyroid disorders
Surfactant protein (SP) deficiency, 62 autoimmune thyroiditis
Swyer syndrome, 455 clinical presentation, 430
Sydenham chorea, 578 diagnosis, 431
Syncope, 508 prevalence, 430
Syndrome of inappropriate ADH secretion (SIADH), 428 treatment, 431
causes, 427 congenital hypothyroidism (see Congenital hypothyroidism)
clinical presentation, 427 function, 429
definition, 427 Graves disease, 431, 432
diagnosis, 427 location, 428
treatment, 427 neonatal thyrotoxicosis, 432, 433
Systemic inflammatory response syndrome (SIRS) criteria, 255 solitary thyroid nodules, 433
Systemic scleroderma, 536 subacute thyroiditis, 431
thyroid-binding globulin deficiency, 429
thyroid cancer, 433
T thyroid storm, 434
Tachycardia, 50, 646 Thyroid storm, 434
Tachypnea, 698 Thyroid-binding globulin deficiency, 430
Taenia solium, 333 Tibial shaft fracture, 499
Takayasu arteritis (TA), 544, 545 Tick paralysis, 575
Tanner staging, 82 Tics, 577
Tarsal coalition, 491–492 Tinea capitis, 862, 863
Tay–Sachs disease, 158–159 Tinea corporis, 510, 863
Teeth grinding, 183 Tinea cruris, 864
Telogen effluvium, 881 Tinea pedis, 864
Temporal skull fracture, 207 Tinea versicolor, 864
Tension headache, 561 Tip-toe walking, 492
Teratogens, 77 T-lymphocytes, 404
Teratology, 103 Toddler fracture, 499, 500
Tertiary syphilis, 320 Toddlers, 746
Testicular appendage torsion, 849 Toilet training, 192, 193
Testicular cancer, 850 Tonsillitis/pharyngitis
Testicular torsion, 52, 848, 849 diagnosis, 626
Tetanus and diphtheria toxoids and acellular pertussis etiology, 626
vaccine (Tdap), 16, 17 symptoms, 626
Tethered cord, 569 treatment, 627
Tethered cord with a terminal lipoma, 998 Torticollis, 470–471
Index 1177
Total anomalous pulmonary venous return (TAPVR), 670 Tricyclic antidepressants (TCAs), 228
Tourette syndrome, 577, 578 Trigonocephaly, 130
Toxic epidermal necrolysis (TEN), 872–873 Triiodothyronine (T3), 429
Toxic shock syndrome (TSS) Trimethoprim-sulfamethoxazole (TMP-SMX), 290, 291, 293, 310,
clinical presentation, 291 311, 315, 317, 330, 933
production, 291 Triple X (XXX) syndrome, 121
risk factors, 291 Trisomy 13/Patau syndrome, 116–118
treatment, 291 Trisomy 18/Edwards syndrome, 116, 117
Toxidromes, 223 Trisomy 21, 376
Toxocara canis, 333 Truncus arteriosus, 669
Toxocara cati, 333 Tuberculin skin test (TST), 323
Toxocariasis, 333 Tuberculosis, see Mycobacterium tuberculosis
Toxoplasma gondii Tuberous sclerosis, 384, 560, 1002
clinical presentation, 330 Tubo-ovarian abscess, 984
diagnosis, 330 Tubular abnormalities
mode of transmission, 330 Bartter syndrome, 815
treatment, 330 cystinosis, 815, 816
Toxoplasmosis, 330 distal RTA type I, 814
Tracheal stenosis, 705 Gitelman syndrome, 815
Tracheoesophageal fistula (TEF), 771 proximal RTA type II, 814
Trachoma RTA, 813, 814
clinical presentation, 306 type IV RTA, 814, 815
diagnosis, 306 Tularemia, 636
treatment, 307 Tumor lysis syndrome
etiology, 306 complications, 382
Traction alopecia, 881 laboratory test, 382
Transcutaneous bilirubin (TcB), 61 treatment, 382
Transient erythroblastopenia of childhood Turcot syndrome, 384
clinical findings, 357 Turner syndrome, 49, 448, 672–674, 782
clinical presentation, 358 abnormal karyotype, 120
etiology, 358 abnormalities, 120
laboratory test, 359 distinctive phenotype, 120
treatment, 359 health supervision and preventive care, 120
Transient hypogammaglobulinemia neonatal findings, 120
of infancy (THI) prevalence, 119
clinical presentation, 408 Turricephaly, 130
diagnosis, 408 Tympanic membrane perforation, 621
etiology, 408 Tympanometry, 620
treatment, 408 Type 1 diabetes mellitus
Transient neonatal pustular melanosis, 855 Addison disease, 457
Transient synovitis, 469 celiac screening, 457
Transient tachypnea of newborn (TTN) clinical presentation, 456
clinical presentation, 64 definition, 455
risk factors, 64 dyslipidemia, 457
treatment, 64 nephropathy screening, 458
Transition milk, 742 retinopathy screening, 457
Transplantation, 894 thyroid screening, 457
Transtentorial herniation, 248 treatment, 456, 457
Transverse myelitis, 570 Type 2 diabetes mellitus
Trauma and burns, 209 causes, 458
Traumatic epidural, subdural and subarachnoid clinical presentation, 458
hemorrhage, 45 depression, 460
Traumatic iritis, 601 diagnosis, 458
Treacher-Collins syndrome, 129–130, 619 dyslipidemia, 459
Treatment errors, 922–923 hypertension, 459
Trematodes (platyhelminthes), 333 nephropathy screening, 459
Treponema pallidum neuropathy screening, 459
clinical presentation, 320 non-alcoholic fatty liver disease, 459
diagnosis, 321 obstructive sleep apnea, 459
mode of transmission, 320 PCOS, 459
treatment, 321 retinopathy screening, 459
Treponema-specific tests, 71 screening, 458
Trichinella spiralis, 333 treatment, 458, 459
Trichinellosis, 333 Type IV RTA, 814, 815
Trichomoniasis, 98 Typhoid fever
Trichotillomania, 183, 881 clinical presentation, 315
Trichuriasis, 332 diagnosis, 315
Trichuris trichiura, 332 mode of transmission, 315
Tricuspid atresia, 667 treatment, 315
1178 Index
U vesicoureteral reflux
U.S. Preventive Services Task Force (USPSTF), antibiotic prophylaxis, 844
1020 clinical background, 842
Ulcerative colitis, 778 clinical presentation, 843
Ulnar polydactyly, 467 diagnosis, 843
Ulnar (postaxial) polydactyly, 467 indications, 844
Umbilical cord care, 39 International Classification System, 843
Umbilical granuloma, 51 management, 843
Umbilical hernia, 50 Urticaria, 871
Uncal herniation, 248 causes, 394
Unconjugated hyperbilirubinemia chronic urticaria
causes, 60 causes, 395
Crigler-Najjar syndrome type 1, 60 diagnosis, 395
Crigler-Najjar syndrome type 2, 60 differential diagnosis, 395
Gilbert syndrome, 60 treatment, 395
Unicameral cyst, 502 clinical presentation, 394
Unilateral parotitis, 287 differential diagnosis
Upper airway infection, 199 Erythema multiforme, 394
Upper airway obstruction, 198 Papular urticaria, 394
Upper motor neuron facial nerve palsy, 574 Urticaria pigmentosa, 394
Upper motor neuron lesions (UMNL), 571 incidence, 394
Urachal remnants, 51 treatment, 394, 395
Urea cycle disorders (UCD), 151 Urticaria pigmentosa (UP), 394, 395
Ureterocele, 844, 845 Urticarial vasculitis, 395
Ureteropelvic junction (UPJ) obstruction, 844 Usher syndrome, 619
Urethral injuries, 852 Usual and unusual grief reaction, 887
Urinalysis (UA) screening, 26 Uveitis, 529
Urinary incontinence, 846
Urinary tract infection (UTI)
acute management, 842 V
clinical background, 841 Valacyclovir, 935
clinical presentation, 842 Valganciclovir, 935
definition, 841 Vancomycin, 934–935
imaging, 842 Varicella (VAR) vaccine, 20
recurrent, 842 Varicella zoster immune globulin (VariZIG), 20, 21, 275
risk factor, 841 Varicella-zoster virus (VZV)
Urology, 1120–1122 epidemiology, 274
balanoposthitis, 847 herpes zoster (shingles), 275
bladder exstrophy, 846 prevention, 275, 276
circumcision, 847, 848 treatment, 275
cryptorchidism, 849, 850 Varicoceles, 850
female urethral prolapse, 845 Vascular anomalies
hydroceles, 850 AVMS, 568
hypospadias, 846 cerebral venous thrombosis, 569
inguinal hernia, 851 stroke, 568
kidney stones, 851, 852 vein of Galen, 568
micropenis, 848 Vascular ring/sling, 705
neonatal testicular torsion, 849 Vascular tumors
paraphimosis, 847 infantile hemangiomas, 868–869
phimosis, 847 Kasabach–Merritt phenomenon, 869
posterior urethral valves, 845 Vasculitis
Prune-Belly syndrome, 845–846 AAV, 543
testicular appendage torsion, 849 Behçet disease, 547, 548
testicular cancer, 850 GPA, 543, 544
testicular torsion, 848, 849 HSP, 545–547
ureterocele, 844, 845 MPA, 544
ureteropelvic junction obstruction, 844 TA, 544, 545
urethral injuries, 852 Vasogenic edema, 251
urinary incontinence, 846 Vaso-occlusive crisis
urinary tract infection prevention, 363
acute management, 842 risk factors, 362
clinical background, 841 treatment, 363
clinical presentation, 842 Vegetarian diets, 751
definition, 841 Vein of Galen malformation, 1008
imaging, 842 Velocardiofacial syndrome, 125–126, 696
recurrent, 842 Velopharyngeal insufficiency (VPI), 629
risk factor, 841 Venereal disease research laboratory (VDRL) test, 321
varicoceles, 850 Venom of hymenoptera, 401
Index 1179
Ventilatory support treatment, 276

common indications, 261 human herpesvirus-7, 276
endotracheal tubes human herpesvirus-8, 276
cuffed tube size, 261 human metapneumovirus
intubation selection, 261 clinical presentation, 280
pediatric considerations, 261 epidemiology, 280
uncuffed tube sizes, 261 treatment, 280
pressure control mode, 262 influenza
respiratory failure, 261–263 AAP immunization guidelines, 279
ventilator parameters setting, 262, 263 clinical presentation, 278
VILI prevention, 263 complications, 278
volume control mode, 262 diagnosis, 279
Ventricular fibrillation (VF), 657 epidemiology, 278
Ventricular septal defect (VSD), 663, 664 treatment, 279
Ventricular tachycardia (VT), 657 norovirus and sapovirus
Verruca vulgaris, 874 clinical presentation, 281
Vertebral body osteomyelitis, 470 epidemiology, 281
Vertebral, anorectal, cardiac, tracheo-esophageal, radial, renal, and parainfluenza virus
limb (VACTERL) defects, 140 clinical manifestation, 280
Vertigo, 617 epidemiology, 280
Very low birth weight (VLBW), 35 treatment, 280
Vesicoureteral reflux (VUR) parvovirus B19
antibiotic prophylaxis, 844 clinical presentation, 276, 277
clinical background, 842 incubation period, 276
clinical presentation, 843 mode of transmission, 276
diagnosis, 843 respiratory syncytial virus, 280
indications, 844 rhinoviruses
International Classification System, 843 clinical features, 281
management, 843 epidemiology, 280, 281
Vesiculoulcerative lesions, 273 testing, 281
Viral croup, 702, 703 RNA virus (see RNA virus)
Viral gastroenteritis, 753 rotavirus
Viral infections clinical presentation, 281, 282
adenovirus diagnosis, 282
clinical presentation, 277, 278 epidemiology, 281
incubation period, 277 varicella-zoster virus
laboratory test, 278 epidemiology, 274
mode of transmission, 277 herpes zoster (shingles), 275
respiratory viruses, 278 prevention, 275, 276
arbovirus (see Arbovirus) Viral infections of the skin, 873, 874
avian influenza H5N1 Viral myositis, 468
clinical presentation, 279 Viral vs. bacterial parotitis, 287
epidemiology, 279 Vision screening, 24, 585–600
mode of transmission, 279 Visual acuity, 605
prevention, 279 Visual development, 605
cytomegalovirus Visual response audiometry (VRA), 620
congenital CMV infection, 271 Vitamin A, 738, 739
diagnosis, 271 Vitamin B6, 738
horizontal transmission, 270, 271 Vitamin B12 deficiency, 738
transfusion and transplantation, 271 clinical presentation, 355
treatment, 271 impaired absorption, 355
vertical transmission, 270 inadequate intake, 355
Epstein–Barr virus laboratory test, 355
clinical presentation, 271, 272 sources, 355
complications, 272 transport protein, absence, 355
management, 272 Vitamin C, 739
transmission mode, 271 Vitamin D deficiency, 739
herpes simplex virus causes, 438, 439
clinical manifestations, 273 clinical presentation, 439
epidemiology, 272, 273 diagnosis, 440
herpes gladiatorum, 274 differential diagnosis, 442
herpetic whitlow, 273 laboratory findings, 442
treatment, 274 prevention, 441
HPV (see Human papillomavirus (HPV)) radiography, 440
human herpesvirus type 6 treatment, 440, 441
clinical presentation, 276 vitamin D metabolism, 438, 439
1180 Index
Vitamin E, 739, 740 Wilms tumor, 387, 981

Vitamin K deficiency, 373, 740 clinical presentation, 386
See also Hemorrhagic disease diagnosis, 386
Vitamins epidemiology, 386
biotin, 736 treatment, 387
folate/folic acid, 736 Wilms tumor-aniridia-growth delay-retardation
niacin, 737 (WAGR) syndrome, 124
riboflavin, 737 Wilson disease, 791
thiamin, 737 Wiskott–Aldrich syndrome, 373
vitamin A, 738, 739 causes, 412
vitamin B12, 738 clinical presentation, 412
vitamin B6, 738 diagnosis, 413
vitamin C, 739 treatment, 413
vitamin D, 739 Wolff-Parkinson-White (WPW) syndrome, 648, 653, 655
vitamin E, 739, 740 Wolf–Hirschhorn syndrome, 121–122, 674
vitamin K, 740 Wolman syndrome, 159
Vitiligo, 877 Wound botulism, 302
Vocal cord paralysis (VCP), 695, 696
Vocal fold paralysis, 639
Voiding cystourethrography (VCUG), 843 X
Volvulus, 762, 763 X-linked adrenoleukodystrophy
Vomiting, 765–767 (X-ALD), 160–161
causes of, 766 X-linked agammaglobulinemia
Von Gierke disease, 154 clinical presentation, 408
Von Hippel–Lindau disease, 384 diagnosis, 408
Von Willebrand disease, 374 treatment, 408
Vulnerable child syndrome (VCS), 892–893 X-linked hyper-IgM syndrome (XHIM)
Vulvovaginitis, 326, 327 causes, 414
clinical presentation, 414
diagnosis, 414
W laboratory findings, 414
Waardenburg syndrome, 129, 619 treatment, 414
Warm autoimmune hemolytic anemia X-linked hypophosphatemic rickets, 441
clinical presentation, 367 X-linked Inheritance
laboratory test, 367 causes, 106
treatment, 367 genetic transmission, 106
Water-bottle heart, 680 X-linked dominant diseases, 107
Waterhouse–Friderichsen syndrome, 308 X-linked recessive disease, 106, 107
Water intoxication, 831 X-linked lymphoproliferative (XLP) syndrome
Water-soluble vitamins, 735 clinical presentation, 411
Weber syndrome, 782 diagnosis, 411
Well child visits, 28–29 treatment, 411
West Nile virus XY pure gonadal dysgenesis,
clinical presentation, 288 see Swyer syndrome
diagnosis, 288 XYY syndrome, 119
epidemiology, 288
treatment, 288
Whipworm, 332 Y
White blood cell disorders Yersinia enterocolitica
aplastic anemia, 370 causes, 318
neutropenia (see Neutropenia) clinical presentation, 318
pancytopenia (see Pancytopenia) treatment, 318
Whole blood interferon-gamma release assays (IGRAs), 323
Whole bowel irrigation, 222
Wilkie syndrome, 773 Z
Williams syndrome, 123, 671, 672, 674 Zanamivir, 279
major abnormalities, 123 Zellweger syndrome, 160
minor anomalies, 123, 124 Zinc, 734, 735
prevalence, 123 Zollinger–Ellison syndrome (ZES), 772

Pediatric Board Study Guide A Last Minute Review, 2nd Edition 2020

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Pediatric Board Study Guide A Last Minute Review, 2nd Edition 2020

Uploaded by

Copyright:

Available Formats

Osama I.

Pediatric Board Study Guide

With Best Regards

ISBN 978-3-030-21266-7 ISBN 978-3-030-21267-4 (eBook)

© Springer Nature Switzerland AG 2020

To all the pediatricians who keep on learning for the sake

About the ABP board-certifying exam

How to study for the ABP board-certifying exam

The day of the exam

El Paso, TX, USA Osama Naga

Amr Abdelgawad, MD, MBA Department of Orthopaedic Surgery and Rehabilitation, Texas

Micah A. Jacobs, MD, MPH Department of Urology, University of Texas Southwestern

Jo-Ann O. Nesiama, MD, MS Division of Pediatric Emergency Medicine, Department of

Kenneth Yen, MD, MS Division of Pediatric Emergency Medicine, Department of Pediatrics,

GROWTH • 3–6 months: weight gain is approximately

© Springer Nature Switzerland AG 2020 1

Head circumference Table 1.1 Difference between benign familial macroceph-

Causes  icrocephaly (See Also Chap. 16

Plagiocephaly (Fig. 1.1) [3] • If more than one suture is involved, it is com-

Fig. 1.2 (a) Deformational plagiocephaly; (b) Unilambdoid synostosis

Table 1.2 Difference between deformational plagiocephaly DEVELOPMENTAL MILESTONES

Social/communication Fine motor

Language Social/communication/problem solving

4 Months • Pushes down on legs when feet are on a hard

Language • Attends to sounds and music

Gross motor 9 Months

• Uses sound to get attention

Fine motor • Gets an object from another room upon

Social/communication/problem-solving Gross motor

Gross motor Social/communication/problem-solving

Fine motor • Knows own gender and age

Fine motor Following objects

Social/communication/problem-solving Speech intelligibility

Fig. 1.8 Fine motor

16 months 18 months 2 years 3 years

4 years 41/2 years 5 years 6 years

• Three-word sentences • Smiles spontaneously at a pleasurable sight/

15 mo 18 mo 2 years 3 years (bridge) 4 years (gate) 5 years (stairs)

Catching objects (Fig. 1.10) • Walks well

IMMUNIZATION [6, 7] –– Compare the risks of vaccines to the risks

Administration • Family history of an adverse event after DTaP

• PCV13 is recommended for all children Catch-up vaccination

23-Valent pneumococcal polysaccharide vac-

Special situations: high-risk conditions (Table 1.6) Contraindication

Methods of vaccine administration (Table 1.7) Table 1.7 Methods of vaccine administration

Influenza Vaccines –– Close contacts and caregivers of severely

Table 1.8 Post-exposure to measles and varicella prophylaxis

6–18 months, between 12 and 23 months of Catch-up vaccination

Post-exposure prophylaxis Special situations

Administration • Low-grade fever

Newborn Bilirubin Screening Vision Screening

Fig. 1.11 Pediatric cuff

Hearing Screening • Screening tool at 18 and 24 months (See also

• Renal disease Urinalysis (UA) Screening

Management of lead poisoning, any detectable Sexually Transmitted Diseases

Screening test for HIV  ral Health Screening

Prevention of bacterial transmission ( Streptococcus

• Helmet for bicycle • Children no longer need to use a booster seat

Preventing Gun Accidents Preventing Bicycle Injuries [14]

Preventing Sunburn [15] Preventing Mosquito Bites [16]

Complications of mosquito bites

• Bacterial cellulitis: Differential diagnosis

Infantile Colic Dietary changes may include the following

El Paso, TX, USA Osama Naga

GROWTH • 3–6 months: weight gain is approximately

Causes icrocephaly (See Also Chap. 16

Plagiocephaly (Fig. 1.1) [3] • If more than one suture is involved, it is com-

Table 1.2 Difference between deformational plagiocephaly DEVELOPMENTAL MILESTONES

4 Months • Pushes down on legs when feet are on a hard

Gross motor 9 Months

IMMUNIZATION [6, 7] –– Compare the risks of vaccines to the risks

Influenza Vaccines –– Close contacts and caregivers of severely

Newborn Bilirubin Screening Vision Screening

Hearing Screening • Screening tool at 18 and 24 months (See also

• Renal disease Urinalysis (UA) Screening

Management of lead poisoning, any detectable Sexually Transmitted Diseases

Screening test for HIV ral Health Screening

Preventing Gun Accidents Preventing Bicycle Injuries [14]

Preventing Sunburn [15] Preventing Mosquito Bites [16]

Infantile Colic Dietary changes may include the following

Normal physical findings PEARLS AND PITFALLS

DEFINITIONS Very low birth weight (VLBW)

DELIVERY ROOM CARE [1] –– Chest compressions are required if the

NEWBORN NURSERY CARE Feeding

Hyperbilirubinemia MATERNAL CONDITIONS

• Cutis marmorata (pale mottled skin): Cold J aundice

Caput Succedaneum • Can extend to orbits and neck

EYES young child, includes epiphora, photophobia,

NECK –– Moro response is asymmetrical, with no

• Bradycardia: HR < 100 bpm is abnormal. Abdominal Masses

Abdominal Wall Defects

Diagnosis I nfant of Diabetic Mother (IDM)

• Water and dextrose solutions should not be J aundice in Premature Infants

Unconjugated Hyperbilirubinemia • Conjugated bilirubin level > 20% of the TSB

• A high index of suspicion of possible BIND A BO and Rh Incompatibility (See

ransient Tachypnea of the Newborn

Neonatal Sepsis Initial clinical presentations of infection

ailure to Pass Meconium in the First

–– Breathing may be irregular, and the infant I ntraventricular Hemorrhage (IVH)

Teratogens (Table 2.6) Clinical presentation

PHYSIOLOGICAL CHANGES Menarche: Time of first menstrual bleeding

Sexuality Adolescent Routine Health Visit

Dysfunctional Uterine Bleeding

Ovarian Cyst • Anabolic steroids

Contraception • Smoking (> 35 years of age)