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Vinod K - Bagga, Arvind Paul - Ghai Essential Pediatrics, 9e-CBS Publishers & Distributors - (2018)
Vinod K - Bagga, Arvind Paul - Ghai Essential Pediatrics, 9e-CBS Publishers & Distributors - (2018)
• •
1a r1cs
Ninth Edition
Editors
~
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P rof. Om Prakash Ghai had a distinguished academic tenure at the All India Institute
of Medical Sciences, New Delhi. He started the Department of Pediatrics in 1959
with six beds for children. Under his leadership, the department evolved into a
multispecialty centre of international repute. After his retirement as Dean of the Institute
and Professor and Head of the Department of Pediatrics, he chaired the Department of
Pediatrics at the University College of Medical Sciences, Delhi, where he served until
1991.
Prof. Ghai was President of the Indian Academy of Pediatrics in 1978 and President
of the International College of Pediatrics from 1987to1990. The International Pediatric
Association presented him the prestigious 'Insignia of Merit Medallion' (1977) for his
outstanding contributions to child welfare. The Indian Council of Medical Research
awarded him the Dr Kamla Menon Prize (1983) and Amrut Mody Prize (1985). The
Medical Council of India bestowed on him the Dr BC Roy Memorial Award for 'Eminent Medical Teacher'
(1987). He was awarded honorary fellowships of the American Academy of Pediatrics, the National Academy
of Medical Sciences and the Indian Academy of Pediatrics.
Prof. Ghai served as a short-term consultant to the World Health Organization and Asian Development
Bank. He was a member of the Technical Advisory Group of the Control of Diarrheal Diseases Program of
the World Health Organization (1987-89). He was member of the National Children's Board and several
expert groups of the Government of India, UNICEF and Indian Council of Child Welfare. He was the editor
of Indian Pediatrics and member of the editorial advisory boards of multiple journals.
Prof. Ghai was a teacher par excellence, an inspiring leader and a true visionary. His name shall always
remain etched in the annals of pediatrics of our country.
"J
··~ '
Preface to the Ninth Edition
As we present the ninth edition of Essential Pediatrics, we are humbled by the role this textbook has played
.t"\.. in imparting knowledge in child health to generations of doctors. Four decades ago, late Prof. OP Ghai
foresaw the need for a textbook of pediatrics for medical students of the country and South Asia. Thereafter,. each
new edition has attempted to present updated knowledge to an expanding group of undergraduate and
postgraduate students.
For India, the next three decades offer a never-before window of opportunity to accelerate its economic growth
and emerge as a nation that would banish poverty forever, and attain heights of prosperity and well-beiI\.s:. We
are transitioning through a demographic phase characterized by an exceptionally high young population
constituting a workforce that is available for economic activity and nation-building. This demographic dividend
can be realized only if children and adolescents are healthy, strong and intelligent. Pediatrics, the science and art
of child healthcare, has thus acquired a new meaning and relevance in the context of new India.
With Ayushman Bharat, the nation has committed itself to a comprehensive primary health S)"'$tem and to
ensure financial protection for the vulnerable families in accessing care for children and adults alike. Preventin~
and promotive health and nutrition will gain further ground, and the agenda of health loss due to pneumonia..
diarrhea, other infections, complications of preterm birth and vaccine preYentable diseases would receive even
more attention. Adolescent health and development will be increasingly important in the coming yea~. We are
already witnessing an upsurge in demand for healthcare for chronic systemic diseases, developmental d.iso.nie~..
disabilities and childhood origins of adult diseases. The realization that children have the right to secondary and
tertiary health care has stimulated the development of pediatric superspecialty programs.
The present edition of Essential Pediatrics continues to respond to these developments. The book maintains its
focus on undergraduate medical students. While we ensure that the 'must know' contents are thoroughly covered..
we provide a glimpse of the 'should know' curriculum. We have ensured that the size of the book enables it to be
readable and handy enough for the classroom and the bedside-as Prof. Ghai always reminded u~ Gh'en the
emphasis on updated management of common childhood illnesses, primary care physicians and pediatricians
would find the book useful. As before, there are strong sections on core areas that continue to serve the nt'('\.is o.f
postgraduate students.
A number of changes have been incorporated in this edition. We welcome new authors for chapters on disorders
of development, central nervous system, micronutrients, otorhinolaryngology, poisoning and accidents, and
integrated management of childhood illnesses. Most other chapters, especially on growth, nutritiOJ\, imnmnizatiOl\.
malignancies, genetics, inborn errors of metabolism and infections, have been revised. The CBSiCentrnl App
featuring illustrations, clinical photographs, tables and algorithms shall serve as a useful educ,1tional resource.
The editors are grateful to all the contributing authors for their scholarly inputs and ensuring that the chapters
continue to provide succinct and updated information, meeting the learning needs of students.
We thank our undergraduate and postgraduate students for their suggestions on content. Dr Priyanka
Khandelwal has helped during multiple stages of preparation, ensuring consistent style across chapte~. Dr Aditl
Sinha, Dr Biswaroop Chakrabarty and Dr Jitendra Meena read through several sections and made useful
suggestions.
We thank our colleagues at CBSP&D, Mr YN Arjuna and Ms Ritu Chawla, for ensuring the quality of pul"'llication
of previous and the present editions. We gratefully acknowledge our colleagues at the AIIMS and other centers
for contributing illustrations and the support of our secretaries, Mr Anil Bhutani and Mr Akhilesh Sharma.
We whole-heartedly thank our readers for the trust, support and suggestions.
Vlnod K Paul
ANlndBagga
......~~--~~~~~~--~~~~--.-~·~ · ~-----.~~~..-~.....,....,,_......~~~--_,,.~--~.~_,..._...~~~~~~
'
List of Contributors
Komron Afzal Ashok K Deorarl Modhullka Kabra
Professor Professor and Head Professor
Department of Pediatrics Department of Pediatrics Department of Pediatrics
Jawaharlal Nehru Medical College All India Institute of Medical Sciences Genetics Unit
Allgarh Muslim University New Deihl All India Institute of Medical Sciences
Allgarh New Deihl
lusher R Godbole
AnuJa Agarwata Consultant Pediatric Endocrinologist Sushll K Kabra
Dietitian Assistant Professor, Dr Vasant Power Professor
Department of Pediatrics Medical College, Nashlk Department of Pediatrics
All India Institute of Medical Sciences Director. Harmony Health Hub, Nashlk Division of Pulmonology and Intensive Care
New Delhi All India Institute of Medical Sciences
Sheftall Gulati New Deihl
Ramesh Agarwal Professor
Professor Deportment of Pediatrics Neena Khanna
Department of Pediatrics Division of Neurology Professor
Division of Neonotology All Indio Institute of Medical Sciences Department of Dermatology
All India Institute of Medical Sciences New Deihl All India Institute of Medical Sciences
New Deihl New Deihl
NeerJo Gupta
Varun Alwodhl Assistant Professor Ajay Khero
Senior Resident Deportment of Pediatrics Public Health Specialist and
Kolawatl Soran Children's Hospital Genetics Unit Deputy Commissioner
Lady Hordlnge Medical College All India Institute of Medical Sciences Ministry of Health and Family Welfare
New Delhi New Deihl Government of India. New Delhi
1
Introduction to Pediatrics
Vinod K Paul u~·t="fX~
The branch of medicine that deals with the care of children nephrology, pulmonology, infectious disease, critical care,
and adolescents is pediatrics. This term has roots in the neurology, hemato-oncology, endocrinology and
Greek word pedo pais (a child) and iatros (healer). Pediatrics cardiology). Pediatrics encompasses intensive care of
covers the age group less than 18 years of age. The goal of neonates and children using the most sophisticated
the specialty is to enable a child to survive, remain healthy, technology, on the one hand, and, providing home care
and attain the highest possible potential of growth, to newborns and children, on the other. Child health is
development and intellectual achievement. Child health thus a state-of-the-art clinical science as well as a rich
encompasses approaches, interventions and strategies that public health discipline.
preserve, protect, promote and restore health of children Medical students should possess competencies for the
at individual and population level. A physician who care of healthy and sick children. The agenda of high child
specializes in the healthcare of children and adolescents mortality due to pneumonia, neonatal infections, preterm
is a pediatrician. birth complications, diarrhea, birth asphyxia and vaccine
Children under 15 years of age comprise about 30% of preventable diseases is still unfinished. The benefits of
India's population. Childhood is the state when the human advancing pediatric speciality care must reach all children.
being is growing and developing. It is the age to acquire Besides, an increasing body of knowledge on pediatric
good habits, values and lifestyles that would make origins of non-communicable diseases of the adult is set
children fit, responsible and productive adults and to change the paradigm of child hea lth . Primary
citizens. The family, society and nation are duty-bound prevention and early detection of adult disorders is an
to make children feel secure, cared for, and protected from important goal of pediatrics. Adolescence offers second
exploitation, violence and societal ills. Female chil~r~n face chance in life to shape good lifestyles and prepare for
gender bias in access to healthc~re and .n utnt10n. A adulthood.
civilized society nurtures all its children, girls and boys
alike, with love, generosity and benevolence. HISTORICAL PERSPECTIVE
Child is not a miniature adult. The principles of adult Medical care of children finds place in the ancient Indian,
medicine cannot be directly adapted to children. Pediatric Greek and Chinese systems of health. But as a formal
biology is unique and risk factors of dise~se are distinct. discipline, pediatrics took root in Europe and the US in
Clinical manifestations of childhood diseases ma~ be the 19th century when some of the famous children
different from adults. Indeed, many disorders are unique hospitals were established. BJ Hospital for Children,
to children-these do not occur in adults ..Drug ~osa?es Mumbai was the first child hospital to be established in
. children are spec ifi'c and not a mathematical
m . . derivation India in 1928. Postgraduate diploma in pediatrics was
of adult dosages. Wholesome nutrih?n ~s even more started there in 1944; postgraduate degree programs began
important for children not only to sustam hfe, but also to in the fifties. Pediatrics became an independent subject in
ensure their growth and development. MBBS course in mid-nineties. The first DM program in
neonatology started in 1989 at PGIMER, Chandigarh,
PEDIATRICS AS A SPECIALITY followed by one in pediatric neurology at AIIMS in 2004.
p d. . . f . ting speciality. It encompasses care Half a dozen institutions in the country now run DM
e iatr1cs is a ascma h d and adolescents programs in various pediatric specialities that include
of premature neonates on the one ~ '. h b ch
on the other. The discipline of pediatrics as rant e
d nephrology, pulmonology, critical care, hematology-
. "alities (such as neona o1ogy oncology, oncology, cardiology and endocrinology.
mto well-developed superspec1 '
... ·~ ; t
i
1
2 ~~~~~~~~~~~~~E~s~s~e~n~tl~a~l~Pe~d~i~at~rl~c!s ____________________~~~---~
of life), and the neonatal mortality (NMR) accounts for
CHALLENGE OF HIGH CHILD MORTALITY
70% infant deaths. . .
India has the highest number of child births as well as teady decline m child deaths. U5"-.n-.
There h as b een a S 19 "U\
child deaths for any single nation in the world. Each year, has declined by almost two-thi~d~be~een 9try0and.2015
as many as 26 million babies are born in India. This from 126 to 43 per 1000 live birt s. e co~ . missed
comprises 18% of the global birth cohort. Of the the Millennium Development Goal 4 of achieving D5MR
5.95 million under 5 child deaths in the world in 2015, of b 2015 by just one number. Between 2000 and 2016,
42
1.20 million (20%) occurred in our country. Table 1.1 IMR Jeclined by 50%, while NMR. decreased by 45%
provides the most recent figures on the key child mortality (Fig. 1.l). The early neonatal mortality (deaths under 7
indices. days of life) has been less amenable to change.
At 39 per 1000 live births (2016), under 5 mortality in In 2016, there were 9.8 lakh under-5 deaths and 5.7 lakh
the country is unacceptably high given our stature as an neonatal deaths in the country.
economic, scientific and strategic power. Under 5 mortality National programs focus generally ?n child deaths
rate (USMR) in Japan (3), UK (4), USA (7), Sri Lanka (10), under the age of 5 years (under-5 ~ortahty)'. The USMR,
China (11) and Brazil (16) is worth comparing with that IMR and NMR targets enshrined m the National Health
of India. Great nations not only have negligible child Policy 2017 are depicted in Table 1.2 ·
mortality, but also ensure good health, nutrition,
education and opportunities to their children. Almost 60% Why do Children Ole?
of under 5 deaths occur in the neonatal period (<28 days
The eight important causes of under 5 ~ortality ~'1 0lldren
in India (with % contribution) are: (1) complications of
Table 1.1: Child mortality indices in India in 2016
prematurity (24%), (ii) pneumoni: (13%), _(iii) neonat~l
Indices Rate infections (12%), (iv) diarrhea (11 Yo), (v) birth asphyxia
Under 5 mortality rate (U5MR) 39 per 1000 live births (11 %), (vi) congenital malformations (4%), (vii) measles
Infant mortality rate (IMR) 34 per 1000 live births (3%), and (viii) injuries (3%) (Fig. 1.2). The above causes
Neonatal mortality rate (NMR) 24 per 1000 live births are the proximate conditions that lead to death. Poverty,
Early neonatal mortality rate (ENMR) 18 per 1000 live births
illiteracy, low caste, rural habitat, harmful cultural
practices, and poor access to safe water and sanitation are
Late neonatal mortality rate (LNMR) 06 per 1000 live births
important determinants of child health. Undemutrition
U5MR: Number of deaths under the age of 5 years per 1000 live births
is a critical underlying intermediate risk factor of child
IMR: Number of deaths under the age of 1 year per 1000 live births
mortality, associated with about 45% of under 5 child
NMA: Number of deaths under the age of 28 days per 1000 live births
ENMR: Number of deaths under the age of 7 days per 1000 live births
deaths. Undernutrition causes stunting and wasting,
LNMR: Number of deaths after completing 7 days of age but before predisposes to infections and is associated with adult
28 days per 1000 live births disorders and low economic productivity.
Rg. 1. 1: Trends In neonatal and Infant mortality, sample registration system. IMR Infant mortality rate; NMR neonatal mortall1Y rate
3
Pneumonia 13%
. -- - - -- - Noonolul
pnourncmla 2%
NoCJnolol
D
lnrocllontJ 12%
- Noonotol
nopols ond
111onlno1tln 10%
Diarrhea 10%
Meningitis 2%
Other
disorders 14%
Birth osphyxlo 11 %
Me"J"3% ~
/
Other neonatal 5%
Congenital molformallons
4%
Fig. 1.2: Causes of under-5 child deaths. The area to the right of the dotted line Indicates neonatal conditions
!able 1:2= Child mortality targets in the National Health Policy 2017 The government launched the National Rural Health
Reduce Under Five Mortality Rate (U5MR) to 23 per 1000 live Mission (NRHM) in 2005. This mission included
births by 2025 investment in public health, improvements in health
Reduce Infant Mortality Rate (IMR) to 28 per 1000 live births systems, focus on communities, deccntralis ntion and
by 2019. demand-side il1terventions lo improve effectiveness of the
Reduce Neonatal Mortality Rate (NMR) to 16 per 1000 llve
programs. The RCH program was integrated into the
births by 2025 NRHM, with prime focus on child and maternal health.
Strategics include deployment of more than 900 000
ASHA~; an incrense in AN Ms, nurses and doctors; setting
NATIONAL PROGRAMS ON CHILD HEALTH up of village health and sanitation; s treng thened primary
Child health has been at the core of our health policy. The health cnre infras tructure; strengthened program
Universal Immunization Program launched in 1985 management capacity, es tablishment of patient-welfare
focused on immunization against six diseases committees at faciliti es, and creation of emergency
(tuberculosis, poliomyelitis, diphtheria, pertussis, tetanus transport networks.
and measles). The Diarrhoeal Disease Control Programme In 2013, the government reviewed maternal and child
was initiated in 1981 and Acute Respiratory Infections health program under NRHM and launched a Strategic
Control Programme in 1990. In 1992, India latmched the Approach to Reproductive, Maternal, Newborn, Child and
Child Survival and Safe Motherhood (CSSM) program by Adolescent Health (RMNCH+A) under the XII Plan. The
combining interventions for child survival (immunization, intervention pnckagcs under the RMNCH+A strategy and
control of diarrheal disease, respiratory infections, details nre shown in Table 1.3. ·
vitamin A supplementation, essential newborn care) and With the ndvent of the National Urban Health Mission,
maternal health (antenatal care, deliveries in institutions, the NRHM is now called as National Health Mission
emergency obstetric care). In 1997, the program for family (NHM). The roles of ASHA, A WW and ANM in maternal,
planning and the CSSM program were merged to create newborn nnd child health in national programs are shown
the Reproductive and Child Health Programme. In phase in Table 1.4.
~of the RCH program (2005), adolescent health component In 2014, the country launched India Newborn Action
was added. Pinn (INAP) which commits the country to siJ1gle digit
- 4
Table 1.3: Summary at" maternal, newborn and child health services under NHM-
01
Introduction to Podiatries
Accredited Social Health Activist Accompanying pregnant mother to facility for delivery
Home care of the newborn and post-partum mothers
Facilitating immunization
Promoting complementary feeding
Primary care in diarrhea and pneumonia
Health education
II s
NMR and stillbirth rate by 2030 and lays down strategies FUTURE OF CHILD HEALTH -
to achieve these targets. . ·
The N ahon lS a ddressing child health challenges With
1 Mission Indradhanush, launched in 2014, is a national
immunization drive to attain 90% coverage of 7 vaccines
.
greater d yna nus
m than ever before.
Ith
Investments
te tr
made for health programs and hea sys ms eng ening.
are
th
being
2 I•
Growth
Ramesh Agarwal • Naveen Sankhyan • Vandana Jain
Growth is an essential feature that distinguishes a child placental-fetal unit acts in harmony to provide the needs of
from an adult. The process of growth starts from the time of the fetus.
conception and continues until the child grows into a fully
Genetic potential: Parental traits are usually transmitted to
mature adult. The terms 'growth' and 'development' are
the offspring. Thus, tall parents have tall children; the size
often used together, but are not interchangeable because
of the head is more closely related to that of parents than
they re~resent two different facets of the dynamics of
are the size and shape of hands and feet. Similarly, the
change, i.e. those of quantity and quality.
structure of the chest and fatty tissue has better genetic
The term growth denotes a net increase in the size or mass association than other somatic characteristics.
of tissues. It is largely attributed to multiplication of cells
and increase in the intracellular substance. Hypertrophy Sex: Boys are generally taller and heavier than girls at the
or expansion of cell size contributes to a lesser extent to the time of birth.
process of growth. Fetal hormones: Human fetus secretes thyroxine from the
Development specifies maturation of functions. It is related 12th week of gestation. Thyroxine and insulin have an
to the maturation and myelination of the nervous system important role in regulating tissue accretion and
and indicates acquisition of a variety of skills for optimal differentiation in the fetus . Both hormones are required for
functioning of the individual. normal growth and development, particularly during late
gestation. Glucocorticoids also play an important role,
Growth and development usually proceed concurrently.
primarily towards the end of gestation and influence the
While they are discussed separately, both growth and
prepa~tum 1:1aturation of organs such as liver, lungs and
development are closely related; hence, factors affecting
g~strointes~al tra~t. Growth hormone, though present in
one also tend to have an impact on the other. During early
high levels m fetus, 1s not known to influence fetal growth.
embryonic period of life, an exponential increase in the
number of cells occurs. At the early embryonic stage, fetal Fetal growth factors: A large number of growth factors
cells divide and differentiate to form tissues and organs. In are synthesized locally in fetal tissues, and act principally
the latter half of pregnancy and early childhood, there is ?Y autoc~e .~d paracrine mechanisms. Their prime effect
also an increase in cell size. This manifests as an increase IS on cell d1v1s1on, though they also influence other aspects
in the protein to DNA ratio. The cell size continu~ t~ enlarge of tissue grow th. These factors can be both growth
until about 10 years of age. The body cells remain~ a state promoting or inhibitory. The insulin like growth factor
of dynamic equilibrium; hence aging cells are continuous~y (IGF)-1 and IGF-Il are among t.he most extensively studied
replaced by new cells. The rate of turnover of cells m fetal growth factors.
different tissues is variable. Pl11ce11t11l factors: As in most species, fetal weight directly
correlates with placental weight at term. Fetal grow th is
FACTORS AFFECTING GROWTH highly dependent on the structural and ftmctional integrity
of the placenta. With advancing gestation, the weight of the
Fetal Growth placenta increases to enter to the increased needs of the baby.
Fetal growth is influenced primarily by f~t~l, p~ac:t~.a~d There are important functional and structural dlanges in
maternal factors. In humans, 40% of vanahon in . e ir - the placenta that make this adaptation more efficient. 11\e
Weight · d t0 netic factors while the rest 1s due to total villous surface area increases, the diffusion distance
. 1S ue ge f h n inherent growth decreases, the fetal capillaries dilate and the resistance in
environmental factors. The etus as a .
potential d under normal circumstances, grows into a fetoplacental vasculature falls. This positive remodeling
' an . . d born. The maternal- facilitates nutrient transport across the placenta.
. h ealthy appropriate size new
7
• 8
Matenial factors: The mother's own fetal and childhood During early infancy, exclusive breastfeeding provides
growth and her nutrient intake and body composition at a d equate nu tr1·t·ion, prevents infections and protects 3--
the
the time of conception and during pregnancy, play an . f t f further undernourishment. However, at 5
m an s ram · th inf
important role in determining fetal size. Teenage or months, the common practice of supplementing . e :mts
: ~~~~.,....,.......,-,.--_,----r-y----i---,.---,-,--~~-1-n]-r-~-~m11-nTn11-1 1
~ }µi 1
-30 . u
--~)--1 r.~+ ,~rtr 1 ~·1rrt~ti41~t 11 ~·11111~11;
1
_blr<--:-
! 20 UJ\.rr·ii~c tl~ - ~ J
. ,Y
1
I ~\ I ,_ I ,_ ~~ -L, i
I 1
i 1
I 1
~ f,st~dt '~1t~111:
11 11 ; I •
I
+""'r'!"·!·
10
0 . I ~·ii
ll.'-'-........_._._,__._.__._,'-_._.T ~ ·-,~ ~~''!' Llu1'
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58
Age In months
Fig.. 2.1: Proportion of children with stunting, underweight and wasting from birth to 5 years. ReprOduced With permission from Poul,
et al. Lancet 2011 :377:332-49
Growth
9 -
Chemical agents: Administration of androgenic hormones of early life has permanent effects on structure, physiology
initially accelerates the skeletal growth. However, and metabolism. The "Developmental Origins of Health
androgens cause the epiphyses of bones to close and Diseases; DOHaD; Barker hypothesis" proposes that
prematurely, leading to early cessation of bone growth. alterations in fetal nutrition and endocrine status result
Trau~a: A ~racture at the end of a bone may damage the
growmg ep1physis, and thus hamper skeletal growth.
Social Factors
23
22
21
11
I
20 • I
- I
10 j
10
17
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 b 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
a Age, years Age, years
Fig. 2.2: Normal height velocl1Y (a) girls and (b) boys according to age. Curves for height veloc11Y at 50th centile for early and late
maturers are also depicted. The open arrow heads Indicate the 3rd and 97th centlle for peak height veloci1Y for these indMduals.
Reprinted from J Pedlatr 1985; 107:317-29; with permission from Elsevier
storehouse of energy. It is primarily deposited in the sub- proximal toes in both sexes; and (v) distal and middle
cutaneous adipose tissue. Girls have more subcutaneous
adipose tissue than boys. Moreover, the sites and quantity
of ~dipos~ tissue differs in girls and boys. Girls tend to add
adipose tissue to breasts, buttocks, thighs and back of arms
during adolescence.
phalanges in boys and distal and proximal phalanges in
girls. To determine the skeletal age in infants between 3 and
9 months, a radiograph of shoulder is most helpful. A single
film of hands and wrists is adequate in children between
the ages of 1 and 13 years. For children between 12 and
I
14 years, radiographs of elbow and hip give helpful clues.
SOMATIC GROWTH
Eruption of Teeth
Skeletal Growth
Primary teeth: The teeth in the upper jaw erupt earlier than
Skeletal growth is a continuous process occurring during
those in the lower jaw, except for lower central incisors
the whole of childhood and adolescence. It is steady until
and second molar {Table 2.2).
the pubertal growth spurt when it accelerates and
subsequently slows considerably. The skeleton is mature Permanent teeth: The order of eruption is shown in
once the epiphysis or growth plates at the end of long bones Table 2.2. The first molars are the first to erupt.
~se_to the shaft or diaphysis. This occurs by about 18 years
m girls and 20-22 years in boys. The degree of skeletal ASSESSMENT OF PHYSICAL GROWTH
maturation closely correlates with the degree of sexual
m~turation. A chi.I d who has advanced sexual maturity Weight: The weight of the child in the nude or minimal
will also have earlier skeletal maturation. light clothing is recorded accurately on a lever or electronic
type of weighing scale (Fig. 2.4). Spring balances are Jess
Skeletal maturation is assessed by noting the appearance
accurate. It is important that child be placed in the middle
and fusion of epiphysis at the ends of long bones. Apart
of weighing pan. The weighing scale should be corrected
from this, bone mineral density can be ascertained by dual
energy X-ray absorptiometry [DXA]. This method allows
assessment of bone mineral content and density at different
ages.
,__ .. ~··~_...--
Primary dentition
Time of eruption, months Time of fall, years
Upper Lower Upper Lower
Central incisors 8-12 6-10 6-7 6-7
Lateral incisors 9-13 10-16 7-8 7-8
First molar · 13-19 14-18 9-11 9-11
Canine 16-22 17-23 10-12 9-12
Second molar 25- 33 23-31 10-12 10-12
Permanent teeth
(
Time of eruption, years
r,
.. - . .
I',,,..;~ '
Upper Lower . Upper Lower
First molar 6-7 6-7 First premolar 10-11 10-12
Central incisors 7-8 , 6-7 Second premolar 10-12 10-12
Lateral incls~rs , . 8-9 I 7-8 Second molar 12-13 11-13
Canine 11-12 '
10-12. . Third molar 17-21 17-21
- 12 ~~~~~~~~~~~~~JE~s~s~o~n~tl!al~P~e~d~la~t~rl~c!s__________________________~-----...
Panel 1: Steps In weighing a baby using a digital scale with 5. The footboard shou e
taring faclllty (Fig. 2.5) firmly against it. ..
· th'is pos1t1on.
1. Use the tared weighing method to weigh children who 6 Measure the length m .
cannot stand on the weighing scale • 'th newborns, their knees may not
Note: Be very ge~t1 wi ? 'ble to position both knees
2. Place the weighing scale on a flat, hard, and even surface. straighten fully. If it is not ~ossi . . '
3. Babies should be weighed naked or with minimal clothing. then measure with one leg m pos1t1on.
4. Ask the mother/caregiver to stand In the middle of the scale nlzation Training Course on Child Growth
I h 0 rga
Reference: World Heat ·
(without footwear), feet slightly apart and to remain still. Assessment. Geneva, WHO, 200B.
5. With the mother/caregiver still standing on the scale, press
the tare button.
6. The scale Is tarred when the display shows the number
zero (whlle mother/caregiver is still standing on the scale).
7. Handover the baby to the mother
8. Record the baby's weight that appears on the display.
Note: If the mother Is very heavy (e.g. 100 kg), then a lighter
person should hold the baby on the tared scale.
Reference: World Health Organization. Training Course on Child Growth
Assessment. Geneva, WHO, 2008.
I
Ag. 2.9: Method of measure- Fig. 2.1 O: Measurement of mid-
ment of chest circumference upper arm circumference .
at the level of nipples Note how the anatomical
landmarks ore first located
Fig. 2.7: Method of recording height. (arrows) to accurately measure
Note the erect posture and the bare feet the circumference
placed flat on the ground. The back. of undemutrition. It is also important to take into account the
heels, buttocks, shoulders and occlput gestational age of infants born prematurely. The duration
ore touching the wall
of prematurity is subtracted from the infant's chronological
age. This correction, however, is not required after 2 years
of age.
Weight: The average birth weight of neonates is about 3 kg.
During the first a few days after birth, the newborn loses
extracellular fluid equivalent to about 10% of the body weight.
Most infants regain their birth weight by the age of 10 days.
Subsequently, they gain weight at a rate of approximately
20-40 g per day for the first 3 months of life. Thereafter, they
gain about 400 g weight every month for the remaining part
of the first year. An infant usually doubles his birth weight
Fig. 2.8: Method of recording by the age of S months. The birth weight triples at 1 year and
head circumference is four times at 2 years of age. Thus, the weight at S months,
1 year and 2 years is approximately 6, 9 and 12 kg,
Cliest drcunrference: The chest circumference is measured respectively. The weight of a child at the age of 3 years is
at the level of the nipples, midway between inspiration approximately five times that of the birth weight. At S years,
and expiration (Fig. 2.9). the expected weight can be calculated by multiplying the
birth weight by 6, at 7 years by 7 and at 10 years b y 10. It
Mid-ttpper ann cire11nrference: To measuring the mid-upper follows that the expected weight at 3, 5, 7 and 10 years is
arm circumference, first mark a point midway between the approximately 15, 18, 21 and 30 kg, respectively. On an
tip of acromian process of scapula and the olecranon of ulna, average, a child gains about 2 kg every year between the
whilethechildholdstheleftarmbyhisside(Fig.210).Itshould ages of 3 and 7 years, and 3 kg per year after that till the
be ensured that the tape is just tight enough to avoid any gap pubertal growth spurt begins (Table 2.3).
as well as avoid compression of soft tissues.
Table 2.3: Ai)proximate anthropometric values ·by -ag·e
Nonnal Growth Age Weight {kg) Length or Head circum-
height {cm) ference {cm)
It is difficult to precisely define the normal_Pattem o~ gro~.
Generally, it implies an average of rea~gs obtam~d ~a Birth 3 50 34
group of healthy individuals, alo~g with ~ pemuss1ble 6 months 6 (doubles) 65 43
range of variation, ie. between the third .and_runetr-seventh 1 year 9 (triples) 75 46
percentiles. Most healthy children mamtam their growth 2 years 12 (quadruples) 90 48
percentile on the growth charts as the yea~~ pass by. 95 49
3 years 15
Significant deviation in a child's plotted position on the
4 years 16 100 50
growth chart can be due to a recent illness or over- or
·son of different observations
Lengt1z or heig1tt: The infant measures approximately 50 cm Z-scor~ al~o~s comlar~xample, one can compare the
at birth, 60 cm at 3 months, 65 cm at 6 months 70 cm at between mdivi~uals.f or individuals by obtaining the
9 months, 75 cm at 1 year and 90 cm at 2 years. A normal height and weight 0 two
Indian child is 100 cm tall at the age of 4 years. Thereafter, respective z-scores.
the child gains about 6 cm in height every year, until the
age of 12 years. After this, increments in height vary Growth Standards
according to the age at the onset of puberty. There is a Growth standards represent nor.ms of growth and can
marked acceleration of the growth during puberty. · t bular or graphical manner. These are
be presented m a 1 'tud" I t d'
Head circumference (HC): Head growth is rapid, especially obtained by either cross-sectiona1or ongi . ma s u ies
. lations Based on data obtamed from US
in the first half of infancy. It reflects the brain growth during m 1arge popu · H h S . .
this period. The head growth slows considerably thereafter. children, the National Center fo~ ea 1t tahshcs
Beginning at 34 cm at birth, the head circumference (NCHS) developed growth charts m 1977. In the year
increases approximately 2 cm per month for first 3 months, 2000, revised growth charts provided by CDC offered an
1 cm per month between 3 and 6 months and 0.5 cm per improved tool to assess child health. However, these
month for the rest of the first year of life. The head charts were based on data obtained from US children
circumference is approximately 40 cm at 3 months, 43 cm who were formula fed .
at 6 months, 46-47cmat1year,48 cm at 2 years. By 12 years, Sensing the need for more internationally applicable
it is 52 cm. growth standards, the WHO conducted the 'Multicentre
Chest circumference: The circumference of chest is about Growth Reference Study' (MGRS) and published new growth
3 cm less than the head circumference at birth. The charts for infants and children up to 5 years of age in 2006.
circumference of head and chest are almost equal by the The MGRS was a community-based, multi-country project
age of 1 year. Thereafter, the chest circumference exceeds conducted in Brazil, Ghana, India, Norway, Oman and the
the head circumference. United States. The children included in the study were raised
in environment that minimized constraints to growth such
Body mass index (BMI): The formula to calculate BMI is
2 as poor nutrition and infection. In addition, their mothers
weight (kg) /height (meter) • BMI is primarily used to assess
obesity. followed healthy practices such as breastfeeding their
children and did not smoke during and after pregnancy.
Growth Charts These WHO child growth standards are unique on several
counts. They provide data on 'how children should grow',
If the growth measurements are recorded in a child over a and go beyond the traditional descriptive references. The
period of time and are plotted on a graph, the deviation in new s~andards make breastfeeding the biological norm and
the growth profile of the child from the normal pattern of
establishes the breastfed infant as the normative growth
growth for that age can be easily interpreted. This is a
model. The pooled sample from the six participating countries
satisfactory tool to diagnose deviation of growth from
makes it a truly international standard and reiterates the
normal. Allowed normal range of variation in observations
is conventionally taken as values between 3rd and 97th fac~ that c:J:illd populations grow similarly across the world's
percentile curves. Percentile curves represent frequency maior regions when their needs for heal th and care are met.
distribution curves. For example, 25th percentile for height Th.ese standar~ also include new growth indicators beyond
in a population would mean that height of 75% of hei~t and ':eight that are particularly useful for monitoring
individuals is above and 24% are below this value. One the mcreasmg epidemic of childhood b "t has
kinf0 ld thi kn o esi y, sue
standard deviation (SD) above the mean coincides with s c ess. The study's longitudinal nature further
84th percentile curve. Likewise 16th percentile curve allows. the development . of growth ve1ocity . stand ar ds,
represents one SD below the mean. Values between third enabl· mg
hin the early
F' identification o un d er or over·
f
and 97th percentile curve correspond to mean ±2 SD. noUflS. ent. igures 2 ·11to2.20 provide percentile curves
f~r weight, length ~r height, weight for height and head
Z-scores: In a population with observations in a typical circumference for girls and boys up t 5 f b ed
Gaussian (normal) distribution, any individual value can WHO MGRS o years o age as
odnt gth st~dards. Tables 2.4 to 2.8 summarize the
be expressed as how many SDs it lies above or below the a a on 1en , weight and h ead circumference
. for these
mean. This is the Z-score for that observation. Thus, if a children.
child's weight is at 2 SD below the mean, it is equivalent to Growth standards _are not available for children older
-2 Z. If the value lies above the mean, Z-score is positive,
than~ years. The Indian Academy of Pediatries (IAP) has
otherwise it is negative. The formula for calculating the
provided updated growth charts for children 5 to 18 vears,
Z-scoreis:
based on data from 33148 children (Table 2.9 and 'Z.lO).
· Observed value - mean value The·charts can also be downloaded fr h tp· 11· • d · orgl
Z-score= - - - - - - - - - - -
Standard deviation Revzsed-IAP-Growth-Charts-2015.php.om t .11 zapm 111.
Growth I 1s II
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Fig. 2.19: Head circumference (girls) from birth to 5 years (percentiles)
lI
3.4 3.9 4.5 5.1 5.8 6.6
2 3.8 48.9 60.8 52.8 54.7 56.7 58.6 60.6
4.3 4.9 5.6 6.3 7.1 8.0
3 4.4 52.4 54.4 56,4 56.4 60.4 62.4 64.4
5.0 5.7 6.4 7.2 8.0 9.0
4 4.9 55.3 57.3 59.4 61.4 63.5 65.5
5.6 6.2 7.0 7.8 8.7 9.7 67.6
5 5.3 57.6 59.7 61 .8 63.9 66.0 68.0 70.1
6.0 6.7 7.5 8.4 9.3
6 10.4 59.6 61.7 63.8 65.9 68.0 70.1 72.2
5.7 6.4 7. 1 7.9 8.8 9.8 10.9 61 .2 63.3 65.5 67.6 69.8 71 .9 74.0
7 5.9 6.7 7.4 8.3 9.2 10.3 11 .4 62.7 64.8 67.0 69.2 71 .3 73.5
8 6.2 6.9 7.7 8.6 75.7
9.6 10.7 11.9 64.0 66.2 68.4 70.6 72.8 75.0
9 6.4 7.1 8.0 8.9 77.2
9.9 11 .0 12.3 65.2 67.5 69.7 72.0 74.2
10 6.6 7.4 8.2 9.2 76.5 78.7
10.2 11.4 12.7 66.4 68.7 71 .0 73.3 75.6
11 6.8 7.6 8.4 9.4 77.9 80.1
10.5 11 .7 13.0 67.6 69.9 72.2 74.5 76.9
12 6.9 7.7 8.6 9.6 79.2 81.5
10.8 12.0 13.3 68.6 71 .0 73.4 75.7 78.1
13 7.1 7.9 8.8 9.9 80.5 82.9
11.0 12.3 13.7 69.6 72.1 74.5 76.9 79.3
14 7.2 8.1 9.0 10.1 81.8 84.2
11.3 12.6 14.0 70.6 73.1 75.6 78.0 80.5
15 7.4 8.3 9.2 10.3 83.0 85.5
11.5 12.8 14.3 71 .6 74.1 76.6 79.1
16 7.5 8.4 9.4 81.7 84.2 86.7
10.5 11.7 13.1 14.6 72.5 75.0 77.6
17 7.7 8.6 9.6 80.2 82.8 85.4 88.0
10.7 12.0 13.4 14.9 73.3 76.0
18 7.8 8.8 78.6 81.2 83.9 86.5 89.2
9.8 10.9 12.2 13.7 15.3 74.2
19 8.0 8.9 76.9 79.6 82.3 85.0 87.7 90.4
10.0 11.1 12.5 13.9 15.6 75.0
20 8.1 9.1 77.7 80.5 83.2 86.0 88.8 91 .5
10.1 11.3 12.7 14.2 15.9 75.8
21 8.2 78.6 81 .4 84.2 87.0 89.8 92.6
9.2 10.3 11 .5 12.9 14.5 16.2
22 8.4 76.5 79.4 82.3 85.1 88.0 90.9 93.8
9 .4 10.5 11.8 13.2 14.7 16.5
23 8.5 77.2 80.2 83.1 86.0 89.0 91 .9 94.9
9.5 10.7 12.0 13.4 15.0 16.8 78.0
24 8.6 81 .0 83.9 86.9 89.9 92.9 95.9
9.7 10.8 12.2 13.6 15.3 17.1 78.7 81.7 84.8 87.8 90.9 93.9 97.0
Weight-for-age, kg
Height-for-age, cm
24
78.0 81 .0 64.1 87.1 90.2 93.2 96.3
25 8.8 9.8 11.0 12.4 13.9 15.5 17.5 78.6 81 .7 84.9 88.0 91 .1 94.2
26 8.9 10.0 11.2 12.5 14.1 15.8 97.3
17.8 79.3 82.5 85.6 88.8 92.0
27 9.0 10.1 11 .3 12.7 14.3 95.2 98.3
16.1 18.1 79.9 83.1 86.4 89.6
28 9.1 10.2 11 .5 92.9 96.1 99.3
12.9 14.5 16.3 18.4 80.5 83.8 87.1
29 9.2 90.4 93.7 97.0 100.3
10.4 11 .7 13.1 14.8 16.6 18.7 81.1 84.5
30 87.8 91 .2 94.5 97.9 101.2
9.4 10.5 11.8 13.3 15.0 16.9 19.0 81.7 85.1 88.5 91.9 95.3 98.7 102.1
31 9.5 10.7 12.0 13.5 15.2 17.1 19.3 82.3 85.7 89.2 92.7 96.1 99.6
32 9.6 10.8 12. 1 13.7 15.4 17.4 19.6 103.0
82.8 86.4 89.9 93.4 96.9 100.4
33 9.7 10.9 12.3 13.8 15.6 17.6 103.9
19.9 83.4 86.9 90.5 94.1 97.6
34 9.8 11.0 12.4 14.0 101 .2 104.8
15.8 17.8 20.2 83.9 87.5 91.1 94.8
35 9.9 11.2 98.4 102.0 105.6
12.6 14.2 16.0 18.1 20.4 84.4 88.1 91.8
36 95.4 99.1 102.7 106.4
10.0 11.3 12.7 14.3 16.2 18.3 20.7 85.0 88.7
37 92.4 96.1 99.8 103.5 107.2
10.1 11 .4 12.9 14.5 16.4 18.6 21.0 85.5 89.2
38 93.0 96.7 100.5 104.2 108.0
10.2 11.5 13.0 14.7 16.6 18.8 21.3 86.0 89.8 93.6
39 97.4 101.2 105.0 108.8
10.3 11.6 13.1 14.8 16.8 19.0 21.6 86.5 90.3 94.2
40 98.0 101 .8 105.7 109.5
10.4 11.8 13.3 15.0 17.0 19.3 21.9 87.0 90.9 94.7
41 98.6 102.5 106.4 110.3
10.5 11.9 13.4 15.2 17.2 19.5 22.1 87.5 91.4 95.3
42 99.2 103.2 107.1 111.0
10.6 12.0 13.6 15.3 17.4 19.7 22.4 88.0 91.9
43 95.9 99.9 103.8 107.8 111.7
10.7 12.1 13.7 15.5 17.6 20.0 22.7 88.4 92.4 96.4
44 100.4 104.5 108.5 112.5
10.8 12.2 13.8 15.7 17.8 20.2 23.0 88.9 93.0
45 97.0 101.0 105.1 109.1 113.2
10.9 12.4 14.0 15.8 18.0 20.5 23.3 89.4 93.5
46 97.5 101.6 105.7 109.8 113.9
11.0 12.5 14.1 16.0 18.2 20.7 23.6 89.8 94.0
47 98.1 102.2 106.3 110.4 114.6
11.1 12.6 14.3 16.2 18.4 20.9 23.9 90.3 94.4
48 98.6 102.8 106.9 111 .1 115.2
11.2 12.7 14.4 16.3 18.6 21.2 24.2 90.7 94.9
49 99.1 103.3 107.5 111.7 115.9
11.3 12.8 14.5 16.5 18.8 21.4 24.5 91.2 95.4
50 99.7 103.9 108.1 112.4 116.6
11.4 12.9 14.7 16.7 19.0 21 .7 24.8 91.6
51 95.9 100.2 104.4 108.7 113.0 117.3
11.5 13.1 14.8 16.B 19.2 21.9 25.1 92.1
52 96.4 100.7 105.0 109.3 113.6 117.9
11 .6 13.2 15.0 17.0 19.4 22.2 25.4 92.5
53 96.9 101.2 105.6 109.9 114.2 118.6
11 .7 13.3 15.1 17.2 19.6 22.4 25.7
54 93.0 97.4 101 .7 106.1 110.5 114.9 119.2
11.8 13.4 15.2 17.3 19.8 22.7 26.0
55 93.4 97.8 102.3 106.7 111.1 115.5 119.9
11.9 13.5 15.4 17.5 20.0 22.9 26.3
56 93.9 98.3 102.8 107.2 111.7 116.1 120.6
12.0 13.6 15.5 17.7 20.2 23.2 26.6
57 94.3 98.8 103.3 107.8 112.3 116.7 121 .2
12.1 13.7 15.6 17.8 20.4 23.4 26.9
58 94.7 99.3 103.8 108.3 112.8 117.4 121.9
12.2 13.8 15.8 18.0 20.6 23.7
59 27.2 95.2 99.7 104.3 108.9 113.4
12.3 14.0 15.9 20.8 118.0 122.6 I
so 12.4
18.2 23.9 27.6 95.6 100.2 104.8 109.4 114.0 118.6 123.2 I
14.1 16.0__ 18.3 21 .0 24.2 27.9 96.1 100.7 105.3 110.0 114.6 119.2 123.9 I
WHO: MGRS
- 22
Table 2.GA: Weight-for-length/height (kg) in girls and boys 0-5 years of age )
Length Weight (kg) Girls Length Weight (kg 8 ; ;
(cm) -3SD -2SD -1 SD Median 1 SD 2 SD 3 SD (cm) -3 SD -2 SD -1 SD Median 0 2SD 3SD
45.0 1.9 2.1 3.0 3.a
~·: 2.7
I
2.3 2.5 2.7 3.0 3.3 I 45.0 1.9 2.0 2.2
45.5 2.0 2.1 2.8 3.1 3.4
2.3 2.5 2.8 3.1 3.4 : 45.5 1.9 2.1 2.3 2' 6
46.0 2.0 2.2
~:: ~:~ ~:~ ;:~ :~:~ ~:~ ~:~ ~:: 2:~
2.9 3.1 3.5
46.5
47.0
2.1
2.2
2.3
2.4
;:; 3.0
3.0
3.2
3.3
3.6
2.6 2.8 3.1 3.4 3.7 47.0 2.1 2.3 2.5 2. 3.7
47.5 2 .2 2.4 3.1 3.4
2.6 2.9 3 .2 3.5 3.8 47.5 2.2 2.4 2.6 2.9 3.8
48.0 2.3 2.5 3.2 3.6
2.7 3.0 3.3 3 .6 4.0 . 48.0 2.3 2.5 2.7 2.9 3.9
48.5 2.4 2.6 3.3 3.7
2.8 3.1 3.4 3.7 4.1 I 48.5 2.3 2.6 2.8 3.0 4.0
49.0 2.4 2.6 3.4 3.8
2.9 3.2 3 .5 3.8 4.2 49.0 2.4 2.6 2.9 3.1 4.2
49.5 2.5 2.7 3.5
3.0 3.3 3.6 3.9 4.3 . 49.5 2 .5 2.7 3.0 3.2 3.9 4.3
50.0 2.6 2.8 4.0
3.1 3.4 3.7 4.0 4.5 50.0 2.6 2.8 3.0 3.3 3.6 4.4
50.5 2.7 2.9 3.2 3.5 3.8 4.2 4.6 50.5 2.7 2.9 3.1 3.4 3 .8 4.1 4.5
51.0 2.8 3.0 3.3 3.6 3.9 4.3 4.8 51.0 2.7 3.0 3 .2 3.5 3 .9 4.2 4.7
51.5 2.8 3.1 3.4 3.7 4.0 4.4 4.9 51.5 2.8 3.1 3.3 3.6 4 .0 4.4 4.8
52.0 2.9 3 .2 3.5 3.8 4.2 4.6 5.1 52.0 2.9 3.2 3.5 3.8 4.1 4.5 5.0
52.5 3.0 3 .3 3.6 3.9 4.3 4.7 5.2 52.5 3.0 3.3 3.6 3.9 4.2 4.6 5.1
53.0 3.1 3.4 3.7 4.0 4.4 4.9 5.4 53.0 3.1 3.4 3.7 4.0 4.4 4.8 5.3
53.5 3.2 3 .5 3 .8 4.2 4.6 5.0 5.5 53.5 3.2 3 .5 3.8 4.1 4.5 4.9 5.4
54.0 3.3 3 .6 3 .9 4.3 4.7 5.2 5.7 54.0 3.3 3.6 3.9 4.3 4 .7 5.1 5.6
54.5 3.4 3 .7 4 .0 4.4 4.8 5.3 5.9 54.5 3.4 3.7 4.0 4.4 4.8 5.3 5.8
55.0 3.5 3.8 4 .2 4.5 5.0 5.5 6.1 55.0 3.6 3.8 4.2 4.5 5.0 5.4 6.0
55.5 3.6 3.9 4 .3 4.7 5.1 5.7 6.3 55.5 3.7 4.0 4.3 4.7 5.1 5.6 6.1
56.0 3.7 4.0 4.4 4.8 5.3 5.8 6.4 56.0 3.8 4.1 4.4 4.8 5.3 5.8 6.3
56.5 3.8 4.1 4.5 5.0 5.4 6.0 6.6 56.5 3.9 4.2 4.6 5.0 5.4 5.9 6.5
57.0 3.9 4.3 4.6 5.1 5.6 6.1 6.8 57.0 4.0 4.3 4.7 5.1 5.6 6.1 6.7
57.5 4.0 4.4 4.8 5.2 5.7 6.3 7.0 57.5 4.1 4.5 4.9 5.3 5.7 6.3 6.9
58.0 4.1 4.5 4.9 5.4 5.9 6.5 7.1 58.0 4.3 4.6 5.0 5.4
58.5 4.2 4.6 5 .9 6.4 7.1
5.0 5.5 6.0 6.6 7.3 58.5 4.4 4.7 5.1 5.6 6.1 6.6 7.2
59.0 4.3 4.7 5.1 5.6 6.2 6.8 7.5 59.0 4.5 4.8 5.3 5.7
59.5 4.4 4.8 6.2 6.8 7.4
5.3 5.7 6.3 6.9 7.7 59.5 4.6 5.0 5.4 5.9 6.4
60.0 4 .5 4.9 7.0 7.6
5.4 5.9 6 .4 7.1 7.8 60.0 4.7 5.1 5.5 6.0 6.5
60.5 4 .6 5.0 7.1 7.8
5.5 6.0 6 .6 7.3 8.0 60.5 4.8 5 .2 5.6 6.1 6.7
61.0 4.7 5.1 7.3 8.0
5 .6 6.1 6 .7 7.4 8.2 61.0 4.9 5.3 5.8 6.3 6.8
61 .5 4.8 5.2 7 .4 8.1
5.7 6.3 6.9 7.6 8.4 61.5 5.0 5.4 5.9 6.4
62.0 4.9 5 .3 7.0 7.6 8.3
5.8 6.4 7.0 7.7 8.5 62.0 5.1 5.6 6.0 6.5
62.5 5.0 5.4 7.1 7.7 8.5
5.9 6.5 7.1 7.8 8.7 62.5 5.2 5.7 6.1 6.7
,63.0 5 .1 5.5 7 .2 7 .9 8.6
6.0 6.6 7.3 8.0 8.8 63.0 5.3 5.8 6.2 6.8
63.5 5.2 5.6 7 .4 8.0 8.8
6.2 6.7 7.4 8.1 9.0 63.5 5.4 5.9 6.4 6.9
64.0 5.3 5.7 7.5 8 .2 8.9
6.3 6.9 7 .5 8.3 9.1 64.0 5.5 6.0 6.5 7.0
64.5 5.4 5.8 7.6 8.3 9.1
6.4 7.0 7.6 8.4 9.3 64.5 5.6 6.1 6.6 7 .1
65.0 5.5 5.9 7.8 8.5 9.3
6.5 7.1 7.8 8.6 9.5 65.0 5.7 6.2 6.7 7.3
65.5 5.5 6 .0 6.6 7.2 7.9 8.7 9.6 65.5 5.8 6.3 6.8 7.4 7.9 8.6 9.4
66.0 5.6 6.1 6.7 7.3 8.0 8.8 9.8 66.0 5.9 6.4 6.9 7.5 8.0 8.7 9.6
66.5 5.7 6.2 6.8 7.4 8.1 9.0 9.9 66.5 6.0 6.5 7.0 7.6 8.2 8.9 9.7
67.0 5.8 6.3 6.9 7.5 8.3 9.1 10.0 67.0 6.1 6.6 7.1 7.7 8.3 9.0 9.9
67.5 5.9 6.4 7.0 7.6 8.4 9.2 10.2 67.5 6.2 6.7 7.2 7.9 8.4 9.2 10.0
68.0 6.0 6 .5 7.1 7.7 8.5 9.4 10.3 68.0 6.3 6.8 7.3 8.0 8 .5 9.3 10.2
68.5 6.1 6.6 7.2 7.9 8.6 9.5 10.5 68.5 6.4 6.9 7.5 8.1 8.7 9.4 10.3
69.0 6.1 6.7 7.3 8.0 8.7 9.6 10.6 69.0 6.5 7.0 7.6 8.2 8.8 9.6 10.5
69.5 6.2 6.8 7.4 8.1 8.8 9.7 10.7 69.5 6.6 7.1 7.7 8.3 8.9 9.7 10.6
70.0 6.3 6.9 7.5 8.2 9.0 9.9 10.9 70.0 6.6 7.2 7.8 8.4 9.0 9.8 10.8
70.5 6.4 6.9 7 .6 8.3 9.1 10.0 11.0 70.5 6.7 7.3 7.9 8.5 9.2 10.0 10.9
71.0 6.5 7.0 7.7 8.4 9.2 10.1 11.1 71.0 6.8 7.4 8.0 8.6 9.3 10.1 11.1
71.5 6.5 7.1 7.7 8.5 9.3 10.2 11 .3 71.5 6.9 7.5 8.1 8.8 9.4 10.2 i12
:12.0 6.6 7.2 7.8 8.6 9.4 10.3 11 .4 72.0 7.0 7.6 8.2 8 .9 9.5 10.4 11 .3
72.5 6.7 7.3 7 .9 8.7 9.5 10.5 11.5 72.5 7.1 7.6 8.3 9.0 9.6 10.5 11.5
73.0 6 .8 7.4 8.0 8.8 9.6 10.6 11.7 73.0 7.2 7.7 8.4 9.1 9.8 10.6 11.6
73.5 6.9 7.4 8.1 8.9 9.7 10.7 11 .8 73.5 7.2 7.8 8.5 9 .2 9.9 10.8 11.a
74.0 6.9 7.5 8.2 9.0 9.8 10.8 11.9 74.0 7.3 7.9 8.6 9.3 10.0 10.9 11.9
74.5 7.0 7.6 8.3 9.1 9.9 10.9 12.0 ' 74.5 7.4 8.0 8.7 9.4 10.1 11.0 12.1
75.0 7.1 7.7 8.4 9.1 10.0 11 .0 12.2 75.0 7.5 8.1 8.8 9.5 10.2 11.2 12.2
75.5. 7.1 7.8 8.5 9.2 10.1 11.1 12.3 75.5 7.6 8.2 8.8 9.6 10.3 11.3 12.3
76.0 7.2 7.8 10.4 11.4 12.5
76.5 7.3
77.0 7.4
7.9
8.0
8.5
8.6
8.7
9.3
9.4
9.5
10.2
10.3
10.4
11.2
11.4
11.5
12.5
12.6
l
12.4 . 76.0 7.6
76.5 • 7.7
77.0 7.8
8.3
8.3
8.4
8.9
9.0
9.1
9.7
9.8
9.9
10.6
10.7
11.5
11.6
12.6
12.7
10.8 11.7 12.8
eontrJ.
--
Growth I 23 I
Table 2.6A: Weight-for-length/height (kg) in girls and boys 0-5 years of age (Contd.)
Length Weight (kg) Girls Length Weight (kg) Boys
(cm) -3SD -2SD -1SD Median 1 SD 2SD 3SD (cm) -3SD -2SD -1SD Median 1 SD 2SD 3SD
77.5 7.4 8.1 8.8 9.6 10.5 11.6 12.8 77.5 7.9 8.5 9.2 10.0 10.9 11.9 13.0
I
78.0 7 .5 8.2 8.9 9.7 10.6 11.7 12.9 78.0 7.9 8.6 9.3 10.1 11.0 12.0 13.1
78.5 7 .6 8.2 9.0 9.8 10.7 11.8 13.0 78.5 8.0 8.7 9.4 10.2 11.1 12.1 13.2
79.0 7 .7 8.3 9.1 9.9 10.8 11.9 13.1 79.0 8.1 8.7 9.5 10.3 11.2 12.2 13.3
79.5 7.7 8.4 9.1 10.0 10.9 12.0 13.3 79.5 8.2 8.8 9.5 10.4 11.3 12.3 13.4
80.0 7.8 8.5 9.2 10.1 11 .0 12.1 13.4 80.0 8.2 8.9 9.6 10.4 11.4 12.4 13.6
80.5 7.9 8.6 9.3 10.2 11 .2 12.3 13.5 80.5 8.3 9.0 9.7 10.5 11.5 12.5 13.7
81.0 8 .0 8.7 9.4 10.3 11.3 12.4 13.7 81 .0 8.4 9.1 9.8 10.6 11.6 12.6 13.8
81.5 8 .1 8.8 9.5 10.4 11.4 12.5 13.8 81.5 8.5 9.1 9.9 10.7 11.7 12.7 13.9
82.0 8 .1 8.8 9.6 10.5 11 .5 12.6 13.9 82.0 8.5 9.2 10.0 10.8 11.8 12.8 14.0
82.5 8 .2 8.9 9.7 10.6 11.6 12.8 14.1 82.5 8.6 9.3 10.1 10.9 11 .9 13.0 14.2
83.0 8.3 9.0 9.8 10.7 11.8 12.9 14.2 83.0 8.7 9.4 10.2 11.0 12.0 13.1 14.3
83.5 8 .4 9.1 9.9 10.9 11 .9 13.1 14.4 83.5 8.8 9.5 10.3 11.2 12.1 13.2 14.4
84.0 8.5 9.2 10.1 11.0 12.0 13.2 14.5 84.0 8.9 9.6 10.4 11.3 12.2 13.3 14.6
84.5 8.6 9.3 10.2 11 .1 12.1 13.3 14.7 84.5 9.0 9.7 10.5 11.4 12.4 13.5 14.7
85.0 8.7 9.4 10.3 11.2 12.3 13.5 14.9 85.0 9.1 9.8 10.6 11.5 12.5 13.6 14.9
85.5 8.8 9.5 10.4 11 .3 12.4 13.6 15.0 85.5 9.2 9.9 10.7 11.6 12.6 13.7 15.0
86.0 8.9 9.7 10.5 11 .5 12.6 13.8 15.2 86.0 9.3 10.0 10.8 11 .7 12.8 13.9 15.2
86.5 9.0 9.8 10.6 11 .6 12.7 13.9 15.4 86.5 9.4 10.1 11.0 11.9 12.9 14.0 15.3
87.0 9.1 9.9 10.7 11 .7 12.8 14.1 15.5 87.0 9.5 10.2 11.1 12.0 13.0 14.2 15.5
87.5 9.2 10.0 10.9 11 .8 13.0 14.2 15.7 87.5 9.6 10.4 11.2 12.1 13.2 14.3 15.6
88.0 9.3 10.1 11.0 12.0 13.1 14.4 15.9 88.0 9.7 10.5 11.3 12.2 13.3 14.5 15.8
88.5 9.4 10.2 11 .1 12.1 13.2 14.5 16.0 88.5 9.8 10.6 11.4 12.4 13.4 14.6 15.9
89.0 9.5 10.3 11 .2 12.2 13.4 14.7 16.2 89.0 9.9 10.7 11 .5 12.5 13.5 14.7 16.1
89.5 9.6 10.4 11.3 12.3 13.5 14.8 16.4 89.5 10.0 10.8 11.6 12.6 13.7 14.9 16.2
90.0 9.7 10.5 11.4 12.5 13.7 15.0 16.5 90.0 10.1 10.9 11.8 12.7 13.8 15 16.4
90.5 9.8 10.6 11.5 12.6 13.8 15.1 16.7 90.5 10.2 11 11 .9 12.8 13.9 15.1 16.5
91 .0 9.9 10.7 11 .7 12.7 13.9 15.3 16.9 91.0 10.3 11 .1 12.0 13.0 14.1 15.3 16.7
91 .5 10.0 10.8 11.8 12.8 14.1 15.5 17.0 91 .5 10.4 11 .2 12.1 13.1 14.2 15.4 16.8
92.0 10.1 10.9 11 .9 13.0 14.2 15.6 17.2 92.0 10.5 11 .3 12.2 13.2 14.3 15.6 17.0
92.5 10.1 11.0 12.0 13.1 14.3 15.8 17.4 92.5 10.6 11.4 12.3 13.3 14.4 15.7 17.1
93.0 10.2 11 .1 12.1 13.2 14.5 15.9 17.5 93.0 10.7 11.5 12.4 13.4 14.6 15.8 17.3
93.5 10.3 11.2 12.2 13.3 14.6 16.1 17.7 93.5 10.7 11.6 12.5 13.5 14.7 16.0 17.4
94.0 10.4 11.3 12.3 13.5 14.7 16.2 17.9 94.0 10.8 11 .7 12.6 13.7 14.8 16.1 17.6
94.5 10.5 11.4 12.4 13.6 14.9 16.4 18.0 94.5 10.9 11.8 12.7 13.8 14.9 16.3 17.7
95.0 10.6 11 .5 12.6 13.7 15.0 16.5 18.2 95.0 11.0 11 .9 12.8 13.9 15.1 16.4 17.9
95.5 10.7 11 .6 12.7 13.8 15.2 16.7 18.4 95.5 11.1 12 12.9 14.0 15.2 16.5 18.0
96.0 10.8 11.7 12.8 14.0 15.3 16.8 18.6 96.0 11.2 12.1 13.1 14.1 15.3 16.7 18.2
96.5 10.9 11.8 12.9 14.1 15.4 17.0 18.7 96.5 11.3 12.2 13.2 14.3 15.5 16.8 18.4
97.0 11.0 12.0 13.0 14.2 15.6 17.1 18.9 97.0 11.4 12.3 13.3 14.4 15.6 17.0 18.5
97.5 11 .1 12.1 13.1 14.4 15.7 17.3 19.1 97.5 11 .5 12.4 13.4 14.5 15.7 17.1 18.7 J
98.0 11 .2 12.2 13.3 14.5 15.9 17.5 19.3 98.0 11.6 12.5 13.5 14.6 15.9 17.3 18.9
98.5 11.3 12.3 13.4 14.6 16.0 17.6 19.5 98.5 11.7 12.6 13.6 14.8 16.0 17.5 19.1
99.0 11.4 12.4 13.5 14.8 16.2 17.8 19.6 99.0 11 .8 12.7 13.7 14.9 16.2 17.6 19.2
99.5 11.5 12.5 13.6 14.9 16.3 18.0 19.8 99.5 11.9 12.8 13.9 15.0 16.3 17.8 19.4
100.0 11.6 12.6 13.7 15.0 16.5 18.1 20.0 100.0 12.0 12.9 14.0 15.2 16.5 18.0 19.6
100.5 11.7 12.7 13.9 15.2 16.6 18.3 20.2 100.5 12.1 13 14.1 15.3 16.6 18.1 19.8
101 .0 11 .8 12.8 14.0 15.3 16.8 18.5 20.4 101 .0 12.2 13.2 14.2 15.4 16.8 18.3 20.0
101.5 11.9 13.0 14.1 15.5 17.0 18.7 20.6 101.5 12.3 13.3 14.4 15.6 16.9 18.5 20.2
102.0 12.0 13.1 14.3 15.6 17.1 18.9 20.8 102.0 12.4 13.4 14.5 15.7 17.1 18.7 20.4
102.5 12.1 13.2 14.4 15.8 17.3 19.0 21 .0 102.5 12.5 13.5 14.6 15.9 17.3 18.8 20.6
103.0 12.3 13.3 14.5 15.9 17.5 19.2 21.3 103.0 12.6 13.6 14.8 16.0 17.4 19.0 20.8
103.5 12.4 13.5 14.7 16.1 17.6 19.4 21.5 103.5 12.7 13.7 14.9 16.2 17.6 19.2 21.0
104.0 12.5 13.6 14.8 16.2 17.8 19.6 21.7 104.0 12.8 13.9 15.0 16.3 17.8 19.4 21.2
104.5 12.6 13.7 15.0 16.4 18.0 19.8 21.9 104.5 12.9 14.0 15.2 16.5 17.9 19.6 21.5
105.0 12.7 13.8 15.1 16.5 18.2 20.0 22.2 105.0 13.0 14.1 15.3 16.6 18.1 19.8 21.7
105.5 12.8 14.0 15.3 16.7 18.4 20.2 22.4 105.5 13.2 14.2 15.4 16.8 18.3 20.0 21 .9
106.0 13.0 14.1 15.4 16.9 18.5 20.5 22.6 106.0 13.3 14.4 15.6 16.9 18.5 20.2 22.1
106.5 13.1 14.3 15.6 17.1 18.7 20.7 22.9 106.5 13.4 14.5 15.7 17.1 18.6 20.4 22.4
107.0 13.2 14.4 15.7 17.2 18.9 20.9 23.1 107.0 13.5 14.6 15.9 17.3 18.8 20.6 22.6
107.5 13.3 14.5 15.9 17.4 19.1 21.1 23.4 107.5 13.6 14.7 16.0 17.4 19.0 20.8 22.8
108.0 13.5 14.7 16.0 17.6 19.3 21 .3 23.6 108.0 13.7 14.9 16.2 17.6 19.2 21 .0 23.1
108.5 13.6 14.8 16.2 17.8 19.5 21 .6 23.9 108.5 13.8 15.0 16.3 17.8 19.4 21.2 23.3
109.0 13.7 15.0 16.4 18.0 19.7 21.8 24.2 109.0 14.0 15.1 16.5 17.9 19.6 21.4 23.6
109.5 13.9 15.1 16.5 18.1 20.0 22.0 24.4 109.5 14.1 15.3 16.6 18.1 19.8 21.7 23.8
110.0 14.0 15.3 16.7 18.3 20.2 22.3 24.7 110.0 14.2 15.4 16.8 18.3 20.0 21 .9 24.1
-· --- - WHO: MGRS
I
Ill 24 Essential Pediatrics --------------
~
----------------====.::.:.:.:~..:..::::;.::;:._-~ arsofage
. . d boys 0-5 ye .. ·-· -
Table 2.68: Weight-for-heighVlength (kg) in g~ls an _ Weight (kg) Boys
Height Weight( kg,,1
Girts Height _ SD -1 SD Median 1 SD 2SD
(cm) -3 SD -2 SD -1 SD Median 1 SD 2 SD 3 SD 2 69
3so
'cm)
t' -3SD 1 .4 8 .1 8.8
9.6
65.0 5.6 6.1 6.6 7.2 97 65 I 5,9 5, 3 ' 7 6 8,2
7.9 8.7
. I 4 7.0 . 8 .9
9.a
::~ ::s ::~
65.5 5.7 6.2 6.7 7.4 8.1 8.9 9.1 9.9
66.0 5 .8 6.3 6.8 7 .5 8.2 9.0 9.80
10 ii ::·5 7 .1 77.78
. 6 .6 7.2 . 9 .2 10.1
66.5 5.8 6 .4 6 .9
~~:~ I :~-5 ::~ 6.~ ~-: ~:~ ::~
7 .6 8.3 9.1
9.4 10.2
67.0 5.9 6.4 7.0 7.7 8.4 9.3
67.5 6 .0 6.5 9 .5 10.4
Table 2.68: Welght·for·helghVlength (kg) In girls and boys o-5 yearn of age (Contd.)
Height
3 SD (cm)
·
-3 SD -2 SD -1 SD
Weight (kg) Soya
Median 1 SD 2SD
I 25
380
-
92.0 10.2 11 .1 12.0 13.1 14.4 15.8 17.4 92.0 10.6 11A 12.3 13.4 14.5 15.8 17.2
92.5
93.0
93.5
94,0 I
94.5
10.3
10.4
10.5
10,6
10.7
11.2
11.3
11.4
11 .5
11.6
12.1
12.3
12.4
12.5
12.6
13.3
13.4
13.5
13.6
13.8
14.5
14.7
14.8
14.9
15.1
16.0
16.1
16.3
16.4
16.6
17.6
17.6
17.9
18.1
18.3
92.5
93.0
93.5
94.0
94.5
10.7
10.8
10.9
11.0
11 . 1
11.5
11.6
11.7
11.8
11.9
12.4
12.6
12.7
12.8
12.9
13.5
13.6
13.7
13.8
13.9
14.6
14.7
14.9
15.0
15.1
15.9
16.0
16.2
16.3
16.5
17.3
17.5
17.6
17.8
17.9
I
95.0 10.8 11 .7 12.7 13.9 15.2 16.7 18.5 95.0 11.1 12.0 13.0 14.1 15.3 16.6 18.1
95.5 10.8 11.8 12.8 14.0 15.4 16.9 18.6 95.5 11.2 12.1 13.1 14.2 15.4 16.7 18.3
I 96,0 10,9 11.9 12.9 14.1 15.5 17.0 18.8 96.0 11.3 12.2 13.2 14.3 15.5 16.9 18.4
96.5 11.0 12.0 13.1 14.3 15.6 17.2 19.0 96.5 11.4 12.3 13.3 14.4 15.7 17.0 18.6
97.0 11.1 12.1 13.2 14.4 15.8 17.4 19.2 97.0 11.5 12.4 13.4 14.6 15.8 17.2 18.8
97.5 . 11.2 12.2 13.3 14.5 15.9 17.5 19.3 97.5 11 .6 12.5 13.6 14.7 15.9 17.4 18.9
96.0 11 .3 12.3 13.4 14.7 16.1 17.7 19.5 98.0 11 .7 12.6 13.7 14.8 16.1 17.5 19.1
98.5 11.4 12.4 13.5 14.8 16.2 17.9 19.7 98.5 11 .8 12.8 13.8 14.9 16.2 17.7 19.3
99.0 11 .5 12.5 13.7 14.9 16.4 18.0 19.9 99.0 11.9 12.9 13.9 15.1 16.4 17.9 19.5
99.5 11 .6 12.7 13.8 15.1 16.5 18.2 20.1 99.5 12.0 13.0 14.0 15.2 16.5 18.0 19.7
100.0 11 .7 12.8 13.9 15.2 16.7 18.4 20.3 100.0 12.1 13.1 14.2 15.4 16.7 18.2 19.9
100.5 11.9 12.9 14.1 15.4 16.9 18.6 20.5 100.5 12.2 13.2 14.3 15.5 16.9 18.4 20.1
101 .0 : 12.0 13.0 14.2 15.5 17.0 18.7 20.7 101.0 12.3 13.3 14.4 15.6 17.0 18.5 20.3
101 .5 1 12.1 13.1 14.3 15.7 17.2 18.9 20.9 101.5 12.4 13.4 14.5 15.8 17.2 18.7 20.5
102.0 ' 12.2 13.3 14.5 15.8 17.4 19.1 21 .1 102.0 12.5 13.6 14.7 15.9 17.3 18.9 20.7
102.5 J 12.3 13.4 14.6 16.0 17.5 19.3 21 .4 102.5 12.6 13.7 14.8 16.1 17.5 19.1 20.9
103.0 I 12.4 13.5 14.7 16.1 17.7 19.5 21.6 103.0 12.8 13.8 14.9 16.2 17.7 19.3 21.1
' 103.5 ' 12.5 13.6 14.9 16.3 17.9 19.7 21.8 103.5 12.9 13.9 15.1 16.4 17.8 19.5 21 .3
' 104.0 ' 12.6 13.8 15.0 16.4 18.1 19.9 22.0 104.0 13.0 14.0 15.2 16.5 18.0 19.7 21 .6
I 104.5 12.6 13.9 15.2 16.6 18.2 20.1 22.3 104.5 13.1 14.2 15.4 16.7 18.2 19.9 21 .8
105.0 12.9 14.0 15.3 16.8 18.4 20.3 22.5 105.0 13.2 14.3 15.5 16.8 18.4 20.1 22.0
105.5 1 13.0 14.2 15.5 16.9 18.6 20.5 22.7 105.5 13.3 14.4 15.6 17.0 18.5 20.3 22.2
1106.0 13.1 14.3 15.6 17.1 18.8 20.8 23.0 106.0 13.4 14.5 15.8 17.2 18.7 20.5 22.5
I
106.5 1 13.3 14.5 15.8 17.3 19.0 21.0 23.2 106.5 13.5 14.7 15.9 17.3 18.9 20.7 22.7
107.0 13.4 14.6 15.9 17.5 19.2 21 .2 23.5 107.0 13.7 14.8 16.1 17.5 19.1 20.9 22.9
107.5 13.5 14.7 16.1 17.7 19.4 21.4 23.7 107.5 13.8 14.9 16.2 17.7 19.3 21.1 23.2
108.0 13.7 14.9 16.3 17.8 19.6 21.7 24.0 108.0 13.9 15.1 16.4 17.8 19.5 21 .3 23.4
108.5 13.8 15.0 16.4 18.0 19.8 21 .9 24.3 108.5 14.0 15.2 16.5 18.0 19.7 21.5 23.7
109.0 ' 13.9 15.2 16.6 18.2 20.0 22.1 24.5 I 109.0 14.1 15.3 16.7 18.2 19.8 21 .8 23.9
109.5 14.1 15.4 16.8 18.4 20.3 22.4 24.8 109.5 14.3 15.5 16.8 18.3 20.0 22.0 24.2
110.0 : 14.2 15.5 17.0 18.6 20.5 22.6 25.1 I 110.0 14.4 15.6 17.0 18.5 20.2 22.2 24.4
110.5 14.4 15.7 17.1 18.8 20.7 22.9 25.4 110.5 14.5 15.8 17.1 18.7 20.4 22.4 24.7
1 111.0 14.5 15.8 17.3 19.0 20.9 23.1 25.7 111.0 14.6 15.9 17.3 18.9 20.7 22.7 25.0
111.5 ' 14.7 16.0 17.5 19.2 21.2 23.4 26.0 111.5 . 14.8 16.0 17.5 19.1 20.9 22.9 25.2
112.0 14.8 16.2 17.7 19.4 21.4 23.6 26.2 112.0 14.9 16.2 17.6 19.2 21 .1 23.1 25.5
112.5 1 15.0 16.3 17.9 19.6 21.6 23.9 26.5 112.5 15.0 16.3 17.8 19.4 21 .3 23.4 25.8
113.0 1 15.1 16.5 18.0 19.8 21.8 24.2 26.8 113.0 15.2 16.5 18.0 19.6 21.5 23.6 26.0
113.5 I 15.3 16.7 18.2 20.0 22.1 24.4 27.1 113.5 15.3 16.6 18.1 19.8 21.7 23.9 26.3
114.0 15.4 16.8 18.4 20.2 22.3 24.7 27.4 114.0 15.4 16.8 18.3 20.0 21.9 24.1 26.6
114.5 15.6 17.0 18.6 20.5 22.6 25.0 27.8 114.5 15.6 16.9 18.5 20.2 22.1 24.4 26.9
115.0 15.7 17.2 18.8 20.7 22.8 25.2 28.1 115.0 15.7 17.1 18.6 20.4 22.4 24.6 27.2
115.5 15.9 17.3 19.0 20.9 23.0 25.5 28.4 115.5 15.8 17.2 18.8 20.6 22.6 24.9 27.5
116.0 16.0 17.5 19.2 21.1 23.3 25.8 28.7 . 116.0 16.0 17.4 19.0 20.8 22.8 25.1 27.8
116.5 i 16.2 17.7 19.4 21.3 23.5 26.1 29.0 : 116.5 16.1 17.5 19.2 21 .0 23.0
23.3
25.4
25.6
28.0
28.3
117.0 16.3 17.8 19.6 21.5 23.8 26.3 29.3 : 117.0 16.2 17.7 19.3 21.2
1 111.5 16.5 18.0 19.8 21.7 24.0 26.6 29.6 117.5 16.4 17.9 19.5 21 .4 23.5 25 .9 28.6
I
118.0 I 16.6 18.2 19.9 22.0 24.2 26.9 29.9 ' 118.0 16.5 18.0 19.7 21.6 23.7 26.1 28.9
118.5 . 16.8 18.4 20.1 22.2 24.5 27.2 30.3 ! 118.5 I 16.7 18.2 19.9 21.8 23.9 26.4 29.2
119.0 I 16.9 18.5 20.3 22.4 24.7 27.4 30.6 I119.o I 16.8 18.3 20.0 22.0 24.1 26.6 29.5
119.5 17.1 18.7 . 20.5 22.6 25.0 27.7 30.9 1119.5 16.9 18.5 20.2 22.2 24.4 26.9 29.8
120.0 ' 17.3 18.9 20.7 22.8 25.2 28.0 31.2 1120.0 i 17.1 18.6 20.4 22.4 24.6 27.2 30.1
L - --·- WHO: MGRS
11 2s
. nd boys o-5 years ----~---
Table 2.7: Body mass index (BMI) for age in 9~~BMI Boys SD 2SD
1 3SD
Age BM/ Girls - -1 SD Median
14.8 16.3
(mo) -3SD -2SD -1 SD Median 1 SD 2 SD 3 SD -3 SD -2 SD
13.4 18.1
11.1 12.2 16.3 17.8 19.4
0 10.1 11 .1 12.2 13.3 14.6 16.1 17.7 10.2 13.6 14.9 19.4
11.3 12.4 16.3 17.8 21.1
1 10.8 12.0 13.2 14.6 16.0 17.5 19.1 15.0 20.0
20.7 12.5 13.7 16.9 18.4 21.8
2 11 .8 13.0 14.3 15.8 17.3 19.0 15.5 20.3
21 .5 13.1 14.3 17.2 18.7 22.1
3 12.4 13.6 14.9 16.4 17.9 19.7 15.8 20.5
20.0 22.0 13.4 14.5 17.3 18.8 22.3
4 12.7 13.9 15.2 16.7 18.3 15.9 20.5
18.4 20.2 22.2 13.5 14.7 17.3 18.8 22.3
5 12.9 14.1 15.4 16.8 16.0
20.3 22.3 13.6 14.7 18.8 20.5 22.3
6 13.0 14.1 15.5 16.9 18.5 16.0 17.3
18.5 20.3 22.3 13.7 14.8 18.7 20.4 22.2
I 7 13.0 14.2 15.5 16.9 15.9 17.3
15.4 16.8 18.4 20.2 22.2 13.6 14.7 18.6 20.3 22.1
8 13.0 14.1 15.8 17.2
12.9 14.1 15.3 16.7 18.3 20.1 22.1 13.6 14.7 18.5 20.1 22.0 I
9 15.7 17.0
12.9 14.0 15.2 16.6 18.2 19.9 21 .9 13.5 14.6 18.4 20.0 21.8
I 10 15.6 16.9
11 12.8 13.9 15.1 16.5 18.0 19.8 21.8 13.4 14.5 18.2 19.8 21.6
15.5 16.8
12 12.7 13.8 15.0 16.4 17.9 19.6 21 .6 13.4 14.4 18.1 19.7 21 .5
14.3 15.4 16.7
13 12.6 13.7 14.9 16.2 17.7 19.5 21.4 13.3 18.0 19.5 21 .3
14.2 15.3 16.6
I 14 12.6 13.6 14.8 16.1 17.6 19.3 21 .3 13.2 17.8 19.4 21.2
14.1 15.2 16.4
I 15 12.5 13.5 14.7 16.0 17.5 19.2 21 .1 13.1
16.3 17.7 19.3 21 .0
16 12.4 13.5 14.6 15.9 17.4 19.1 21.0 13.1 14.0 15.1
16.2 17.6 19.1 20.9
12.4 13.4 14.5 15.8 17.3 18.9 20.9 13.0 13.9 15.0
I 17 16.1 17.5 19.0 20.8
18 12.3 13.3 14.4 15.7 17.2 18.8 20.8 12.9 13.9 14.9
14.9 16.1 17.4 18.9 20.7
. 19 12.3 13.3 14.4 15.7 17.1 18.8 20.7 12.9 13.8
14.8 16.0 17.3 18.8 20.6
! 20 12.2 13.2 14.3 15.6 17.0 18.7 20.6 12.8 13.7
14.7 15.9 17.2 18.7 20.5
21 12.2 13.2 14.3 15.5 17.0 18.6 20.5 12.8 13.7
13.6 14.7 15.8 17.2 18.7 20.4
22 12.2 13.1 14.2 15.5 16.9 18.5 20.4 12.7
12.7 13.6 14.6 15.8 17.1 18.6 20.3
I 23 12.2 13.1 14.2 15.4 16.9 18.5 20.4
15.4 20.3 12.7 13.6 14.6 15.7 17.0 18.5 20.3
24 12.1 13.1 14.2 16.8 18.4
By height By height
Age
(mo) -3 SD -2 SD -1 SD Median 1 SD 2SD 3SD -3SD -2SD -1 SD Median 1 SD 2SD 3SD
24 12.4 13.3 14.4 15.7 17.1 18.7 20.6 12.9 13.8 14.8 16.0 17.3 18.9 20.6
. 25 12.4 13.3 14.4 15.7 17.1 18.7 20.6 12.8 13.8 14.8 16.0 17.3 18.8 20.5
! 26 12.3 13.3 14.4 15.6 17.0 18.7 20.6 12.8 13.7 14.8 15.9 17.3 18.8 20.5
; 27 12.3 13.3 14.4 15.6 17.0 18.6 20.5 12.7 13.7 14.7 15.9 17.2 18.7 20.4
' 28 12.3 13.3 14.3 15.6 17.0 18.6 20.5 12.7 13.6 14.7 15.9 17.2 18.7 20.4
29 12.3 13.2 14.3 15.6 17.0 18.6 20.4 12.7 13.6 14.7 15.8 17.1 18.6 20.3
30 12.3 13.2 14.3 15.5 16.9 18.5 20.4 12.6 13.6 14.6 15.8 17.1 18.6 20.2
31 12.2 13.2 14.3 15.5 16.9 18.5 20.4 12.6 13.5 14.6 15.8 17.1 18.5 20.2
1 32 12.2 13.2 14.3 15.5 16.9 18.5 20.4 12.5 13.5 14.6 15.7 17.0 18.5 20.1
: 33 12.2 13.1 14.2 15.5 16.9 18.5 20.3 12.5 13.5 14.5 15.7 17.0 18.5 20.1
34 12.2 13.1 14.2 15.4 16.8 18.5 20.3 12.5 13.4 14.5 15.7 17.0 18.4 20.0
35 12.1 13.1 14.2 15.4 16.8 18.4 20.3 12.4 13.4 14.5 15.6 16.9 18.4 20.0
36 12.1 13.1 14.2 15.4 16.8 18.4 20.3 12.4 13.4 14.4 15.6 16.9 20.0
18.4
37. 12.1 13.1 14.1 15.4 16.8 18.4 20.3 12.4 13.3 14.4 15.6 16.9 19.9
18.3
38 12.1 13.0 14.1 15.4 16.8 18.4 20.3 12.3 13.3 14.4 15.5 16.8 18.3 19.9
! 39 12.0 13.0 14.1 15.3 16.8 18.4 20.3 12.3 13.3 14.3 15.5 16.8 18.3 19.9
' 40 12.0 13.0 14.1 15.3 16.8 18.4 20.3 12.3 13.2 14.3 15.5 16.8 18.2 19.9
41 12.0 13.0 14.1 15.3 16.8 18.4 20.4 12.2 13.2 14.3 15.5 16.8 18.2 19.9
42 12.0 12.9 14.0 15.3 16.8 18.4 20.4 12.2 13.2 14.3 15.4 16.8 18.2 19.8
43 11 .9 12.9 14.0 . 15.3 16.8 18.4 20.4 12.2 13.2 14.2 15.4 16.7 18.2 19.8
44 11.9 12.9 14.0 15.3 16.8 18.5 20.4 12.2 13.1 14.2 15.4 16.7 18.2 19.8
45 11 .9 12.9 14.0 15.3 16.8 18.5 20.5 12.2 13.1 14.2
18.5 15.4 16.7 18.2 19.8
46 11 .9 12.9 14.0 15.3 16.8 20.5 12.1 13.1 14.2
18.5 20.5 15.4 16.7 18.2 19.8
I 47 11 .8 12.8 14.0 15.3 16.8 12.1 13.1 14.2
11 .8 12.8 14.0 15.3 16.8 18.5 20.6 15.3 16.7 18.2 1·l9
I 48 12.1 13.1 14.1
11 .8 12.8 13.9 15.3 16.8 18.5 20.6 15.3 16.7 18.2 18.9 '
49 12.1 13.0 14.1
11 .8 12.8 13.9 15.3 16.8 18.6 20.7 12.1 15.3 16.7 18.2 19.9
50 · 13.0 14.1
18.6 20.7 15.3 16.7 18.2 1 fl.9
l 51 11 .8 12.8 13.9 15.3 16.8 12.1 13.0 14.1 15.3 16.6 'i 9.9
; 52 11.7 12.8 13.9 15.2 16.8 18.6 20.7 12.0 13.0 14.1 18.2
18.6 15.3 16.6 18.2 ·f.?..9
53 11 .7 12.7 13.9 15.3 16.8 20.8 12.0 13.0 14.1
18.7 20.8 15.3 16.6 18.2 ;:().0
I 54 11.7 12.7 13.9 15.3 16.8 12.0 13.0 14.0
55 11.7 12.7 13.9 15.3 16.8 18.7 20.9 15.3 16.6 18.2 20.0
12.0 13.0 14.0
56 11 .7 12.7 13.9 15.3 16.8 18.7 20.9 15.2 16.6 18.2 20.0
12.0 12.9 14.0
! 57 11 .7 12.7 13.9 15.3 16.9 18.7 21 .0 12.0 15.2 16.6 18.2 20. 1
12.9 14.0
\ 58 11.7 12.7 13.9 15.3 16.9 18.8 21.0 15.2 16.6 18.2 20.1
12.0 12.9 14.0
59 11.6 12.7 13.9 15.3 16.9 18.8 21 .0 12.0 15.2 16.6 18.3 20.2
12.9 14.0 15.2 16.6 18.3 20.2
~ ··- -·- J
- - - -WHO: MGRS
Growth
I 21 -
Table 2.~:
Head circumference for age (cm) in girls and boys 0-5 years of age
Age BM/ Girls - ·- - - -~ I BM/ Boys
, (mo)
' 0
-3 SD
30.3
-2 SD
31 .5
-1 SD Median
32.7
1 SD 2 SD 3 SD l -3 SD -2 SD - 1 SD Median 1 SD
2SD 3SD l
33.9 35.1 36.2 37.4
1 33.0 34.2 35.4 30.7 31.9 33.2 34.5 35.7
36.5 37.7 37.0 38.3
I
2 38.9 40.1 33.8 34.9 36.1 37.3
34.6 35.8 37.0 38.3 38.4 39.6" 40.8
39.5 40.7 41.9 35.6
3 35.8 37.1 38.3 39.5 36.8 38.0 39.1 40.3 41.5 42.6
40.8 42.0 43.3 37.0
4 36.8 38.1 39.3 38.1 39.3 40.5 41.7 42.9 44.1
40.6 41 .8 43.1 44.4
5 37.6 38.9 40.2 38.0 39.2 40.4 41 .6 42.8
41.5 42.7 44.0 44.0 45.2
6 38.3 45.3 38.9 40.1 41.4 42.6
39.6 40.9 42.2 43.5 43.8 45.0 46.2
7 44.8 46.1 39.7 40.9 42.1 43.3
38.9 40.2 41.5 42.8 44.6 45.8 47.0
44.1 45.5 46.8 40.3
8 39.4 40.7 42.0 41 .5 42.7 44.0 45.2 46.4 47.7
43.4 44.7 46.0 47.4
9 39.8 41.2 42.5 40.8 42.0 43.3 44.5 45.8 47.0
43.8 45.2 46.5 48.3
10 40.2 47.8 41.2 42.5 43.7 45.0 46.3
41.5 42.9 44.2 45.6 47.5 48.8
11 46.9 48.3 41 .6 42.9 44.1 45.4
40.5 41.9 43.2 44.6 46.7 47.9 49.2
45.9 47.3 48.6 41.9 43.2 44.5 45.8
12 40.8 42.2 43.5 47.0 48.3 49.6
44.9 46.3 47.6 49.0 42.2
13 41.1 42.4 43.8 43.5 44.8 46.1 47.4 48.6 49.9
45.2 46.5 47.9 49.3 42.5
14 41 .3 42.7 44.1 43.8 45.0 46.3 47.6 48.9 50.2
45.4 46.8 48.2 49.5 42.7
15 41 .5 42.9 44.3 44.0 45.3 46.6 47.9 49.2 50.5
45.7 47.0 48.4 49.8 42.9
16 41.7 43.1 44.5 44.2 45.5 46.8 48.1 49.4 50.7
45.9 47.2 48.6 50.0 43.1
17 41.9 43.3 44.7 44.4 45.7 47.0 48.3 49.6 51 .0
46.1 47.4 48.8 50.2 43.2
. 18 42.1 43.5 44.9 44.6 45.9 47.2 48.5 49.8 51.2
46.2 47.6 49.0 50.4 43.4
19 42.3 43.6 45.0 44.7 46.0 47.4 48.7 50.0 51.4
46.4 47.8 49.2 50.6 43.5
20 42.4 43.8 45.2 44.9 46.2 47.5 48.9 50.2 51.5
46.6 48.0 49.4 50.7 43.7
21 42.6 45.0 46.4 47.7 49.0 50.4 51.7
44.0 45.3 46.7 48.1 49.5 50.9 43.8 45.2 46.5 47.8 49.2 50.5 51.9 "
22 42.7 44.1 45.5 46.9 48.3 49.7 51.1 43.9 45.3 46.6 48.0 49.3 50.7 52.0
23 42.9 44.3 45.6 47.0 48.4 49.8 51.2 44.1 45.4 46.8 48.1 49.5 50.8 52.2
24 43.0 44.4 45.8 47.2 48.6 50.0 51.4 44.2 45.5 46.9 48.3 49.6 51 .0 52.3
25 43.1 44.5 45.9 47.3 48.7 50.1 51.5 44.3 45.6 47.0 48.4 49.7 51 .1 52.5
26 43.3 44.7 46.1 47.5 48.9 50.3 51.7 44.4 45.8 47.1 48.5 49.9 51 .2 52.6
27 43.4 44.8 46.2 47.6 49.0 50.4 51 .8 44.5 45.9 47.2 48.6 50.0 51.4 52.7
28 43.5 44.9 46.3 47.7 49.1 50.5 51 .9 44.6 46.0 47.3 48.7 50.1 51.5 52.9
29 43.6 45.0 46.4 47.8 49.2 50.6 52.0 44.7 46.1 47.4 48.8 50.2 51.6 53.0
30 43.7 45.1 46.5 47.9 49.3 50.7 52.2 44.8 46.1 47.5 48.9 50.3 51.7 53.1
l 31 43.8 45.2 46.6 48.0 49.4 50.9 52.3 44.8 46.2 47.6 49.0 50.4 51.8 53.2
• 32 43.9 45.3 46.7 48.1 49.6 51.0 52.4 44.9 46.3 47.7 49.1 50.5 51.9 53.3
I 33 44.0 45.4 46.8 48.2 49.7 51 .1 52.5 45.0 46.4 47.8 49.2 50.6 52.0 53.4
t 34 44.1 45.5 46.9 48.3 49.7 51.2 52.6 45.1 46.5 47.9 49.3
l 50.7 52.1 53.5
I 35 44.2 45.6 47.0 48.4 49.8 51.2 52.7 45.1 46.6 48.0 49.4 50.8 52.2 53.6
i 36 44.3 45.7 47.1 48.5 49.9 51.3 52.7 45.2 46.6 48.0 49.5 50.9 52.3 53.7
' 37 44.4 45.8 47.2 48.6 50.0 51.4 52.8 45.3 46.7 48.1 49.5 51 .0 52.4 53.8
38 44.4 45.8 47.3 48.7 50.1 51.5 52.9 45.3 46.8 48.2 49.6 51 .0 52.5 53.9
39 44.5 45.9 47.3 48.7 50.2 51.6 53.0 45.4 46.8 48.2 49.7 51 .1 52.5 54.0
40 44.6 46.0 47.4 48.8 50.2 51.7 53.1 45.4 46.9 48.3 49.7 51 .2 52.6 54.1
41 44.6 46.1 47.5 48.9 50.3 51.7 53.1 45.5 46.9 48.4 49.8 51.3 52.7 54.1
42 44.7 46.1 47.5 49.0 50.4 51.8 53.2 45.5 47.0 48.4 49.9 51.3 52.8 54.2
43 44.8 46.2 47.6 49.0 50.4 51.9 53.3 45.6 47.0 48.5 49.9 51 .4 52.8 54.3
t 44 44.8 46.3 47.7 49.1 50.5 51.9 53.3 45.6 47.1 48.5 50.0 51 .4 52.9 54.3
. 45 44.9 46.3 47.7 49.2 50.6 52.0 53.4 45.7 47.1 48.6 50.1 51.5 53.0 54.4
t 46 45.0 46.4 47.8 49.2 50.6 52.1 53.5 45.7 47.2 48.7 50.1 51.6 53.0 54.5
; 47 45.0 46.4 47.9 49.3 50.7 52.1 53.5 45.8 47.2 48.7 50.2 51 .6 53.1 54.5
: 48 45.1 46.5 47.9 49.3 50.8 52.2 53.6 45.8 47.3 48.7 50.2 51 .7 53.1 54.6
' 49 45.1 46.5 48.0 49.4 50.8 52.2 53.6 45.9 47.3 48.8 50.3 51.7 53.2 54.7
~ 50 45.2 46.6 48.0 49.4 50.9 52.3 53.7 45.9 47.4 48.8 50.3 51.8 53.2 54.7
51 45.2 46.7 48.1 49.5 50.9 52.3 53.8 45.9 47.4 48.9 50.4 51 .8 53.3 54.8 .
52 45.3 46.7 48.1 49.5 51 .0 52.4 53.8 46.0 47.5 48.9 50.4 51 .9 53.4 54.8
53 45.3 46.8 48.2 49.6 51 .0 52.4 53.9 46.0 47.5 49.0 50.4 51.9 53.4 54.9
54 45.4 46.8 48.2 49.6 51.1 52.5 53.9 46.1 47.5 49.0 50.5 52.0 53.5 54.9
55 45.4 46.9 48.3 49.7 51 .1 52.5 54.0 46.1 47.6 49.1 50.5 52.0 53.5 55.0
56 45.5 46.9 48.3 49.7 51 .2 52.6 54.0 46.1 47.6 49.1 50.6 52.1 53.5 55.0
57 45.5 46.9 48.4 49.8 51 .2 52.6 54.1 46.2 47.6 49.1 50.6 52.1 53.6 55.1
58 45.6 47.0 48.4 49.8 51 .3 52.7 54.1 46.2 47.7 49.2 50.7 52.1 53.6 55.1
59 45.6 47.0 - 48.5 49.9 51 .3 52.7 54.1 46.2 47.7 49.2 50.7 52.2 53.7 55.2
60 45.7 49.9 51 .3 52.8 - 54.2 46.3 47.7 49.2 50.7 52.2 53.7 55.2
47.1 48.5
WHO-;-MGRS
Table 2.9: Boys aged 5 to 18 years old: IAP charts for weight, height, body mass index (percentiles) (reproduced with permission from Indian Pediatr, 2015;52:47-55)
I
Height (cm) Weight (kg) Body mass index
~ge 23rd 27th SD
'years) 3td 10th 50th 90th 97th SD 3rd 10th 50th 90th 97th SD 3th 5th 10th 50th AE AE
14.3 17.1 21.3 24.2 3.2 12.1 12.4 12.8 14.7 15.7 17.5 1.6
5.0 99.0 102.3 108.9 115.9 119.4 5.7 13.2
18.2 22.9 26.1 2.9 12.2 12.4 12.9 14.8 15.8 17.6 1.5
5.5 101 .6 105.0 111.9 119.0 122.7 5.3 13.8 15.0
19.3 24.6 28.3 3.6 12.2 12.5 12.9 14.9 16.0 17.8 1.8
6.0 1'04.2 .107.7 114.8 122.2 126.0 5.6 14.5 15.8
16.8 20.7 26.6 30.8 3.8 12.3 12.5 13.0 15.0 16.1 18.0 1.8
6.5 106.8 ·110.4 117.8 125.4 129.3 5.5 15.3
17.6 21 .9 28.6 33.4 4.2 12.3 12.6 13.1 15.1 16.3 18.2 1.9
7.0 109.3 113.0 120.7 128.6 132.6 5.9 16.0
131.7 135.9 5.7 16.7 18.5 23.3 30.8 36.2 4.9 12.4 12.7 13.2 15.3 16.5 18.5 2 .2
7.5 111.8 115.7 123.5
139.1 6.3 17.5 19.5 24.8 33.2 39.4 5.7 12.5 12.8 13.3 15.5 16.7 18.8 2.5
8.0 114.3 118.2 · 126.4 134.8
137.8 142.2 6.1 18.3 20.5 26.4 35.7 42.6 6.5 12.6 12.9 13.4 15.7 17.0 19.2 2.8
8.5 116.7 120.8 129.1
119.0 . 123.2 131 .8 140.7 145.3 6.4 19.1 21.5 27.9 38.0 45.5 6.3 12.7 13.0 13.5 15.9 17.3 19.6 2.6
9.0
9.5 121 .3 125.6 134.5 143.7 148.3 6.4 19.9 22.4 29.4 40.5 48.6 7.0 12.8 13.1 13.7 16.2 17.6 20.1 2.8
10.0 123.6 128.1 137.2 146.6 151 .4 6.8 20.7 23.5 31.1 43.0 51.8 7.9 12.9 13.2 13.8 16.4 18.0 20.5 3.1
10.5 125.9 130.5 139.9 149.5 154.4 6.5 21.6 24.6 32.8 45.8 55.2 8.3 13.0 13.3 14.0 16.7 18.3 21.0 3 .2
11 .0 128.2 ' 133.0 142.7 152.5 157.5 7.6 22.6 25.9 34.7 48.7 58.7 8.9 13.1 13.5 14.1 17.0 18.7 21.5 3.2
11.5 130.7 135.6 145.5 155.6 160.6 7.3 23.8 27.3 36.9 51 .8 62.5 9.3 13.2 13.6 14.3 17.3 19.1 22.1 -3.3
12.0 .133.2 138.3 148.4 158.6 163.7 8.1 24.9 28.7 39.0 54.8 66.1 10.0 13.3 13.8 14.5 17.7 19.5 22.6 3 .4
12.5 135.7 141 .0 151.4 161.7 166.8 7.9 26.1 30.2 41 .2 57.8 69.5 10.6 13.5 13.9 14.6 17.9 19.8 23.0 3.6
13.0 138.3 143.7 154.3 164.7 169.9 9.0 27.5 31.8 43.3 60.7 72.6 11.3 13.6 14.0 14.8 18.2 20.2 23.4 3.5
13.5 140.9 146.4 157.2 167.6 172.7 8.4 29.0 33.6 45.7 63.6 75.6 11.4 13.7 14.2 14.9 18.5 20.5 23.8 3.7
14.0 143.4 149.0 159.9 170.3 175.4 9.0 30.7 35.5 48.2 66.3 78.3 12.1 13.8 14.3 15.1 18.7 20.8 24.2 3.7
14.5 145.8 151.5 162.3 172.7 177.7 7.8 32.6 37.7 50.8 69.1 80.9 11 .6 14.0 14.5 15.3 19.0 21 .1 24.5 3.5
15.0 148.0 153.7 164.5 174.8 179.7 7.9 34.5 39.8 53.1 71 .5 83.1 12.1 14.2 14.7 15.5 19.3 21.4 24.9 3.7
15.5 150.0 155.7 166.5 176.5 181.4 6.6 36.1 41.6 55.2 73.4 84.7 11 .2 14.4 14.9 15.8 19.6 21.7 25.2 3 .4
16.0 151.8 157.4 168.1 178.0 182.7 7.2 37.5 43.1 56.8 74.6 65.8 12.2 14.6 15.1 16.0 19.9 22.0 25.5 3.7
16.5 153.4 159.1 169.6 179.3 183.8 6.7 38.7 44.4 58.2 76.1 86.B 12.6 14.9 15.4 16.3 20.2 22.4 25.8 3.8
17.0 155.0 160.6 171.0 180.4 184.8 6.9 39.8 45.6 59.5 77.1 87.5 12.3 15.1 15.6 16.6 20.5 22.6 26.0 3.8
17.5 156.6 162.1 172.3 181.5 185.8 6.1 40.8 46.7 60.6 77.8 88.0 12.3 15.4 15.9 16.8 20.8 22.9 26.3 3.6
18.0 158.1 163.6 173.6 182.5 186.7 6.9 41.8 47.7 61.6 78.6 88.4 11.3 15.6 16.2 17.1 21 .1 23.2 26.6 3.2
23rd AE: equivalent to BMI of 23 in adults (overweight); 27th AE: equivalent to BMI of 27 in adults (obesity) IAP
Tabre 2.10: Girls aged 5 to 18 years old: IAP charts tor weight, height, body mass index (percentiles) (reproduced with permission from Indian Pediatr 2015;52:47-55)
Age -- . - Height (cm) - - - · · Weight (kg) BOdy Mass Index
23 27
(yeatS) 3rd 10th 50th 90th 97th SD 3rd 10th 50th 90th 97th SD 3rd 5th 10th 50th rd th SD
AE AE
5.0 97.2 100.5 107.5 115.2 119.3 5.4 12.3 13.4 16.4 21.3 25.0 2.5 11.9 12.1 12.5 14.3 15.5 18.0 1.4
5.5 99.8 103.2 110.5 118.3 122.5 5.7 13.0 14.3 17.6 22.9 27.0 3.5 11 .9 12.2 12.6 14.4 15.7 18.3 1.7
6.0 102.3 106.0 113.5 121.5 125.6 5.8 13.7 15.1 18.7 24.6 29.1 3.4 12.0 12.2 12.7 14.5 15.9 18.6 1.7
6.5 104.9 108.7 116.5 124.6 128.7 5 .5 14.4 15.9 19.9 26.3 31.2 4.1 12.1 12.3 12.8 14.7 16.1 18.9 2.0
7 .0 107.4 111.4 119.4 127.7 131 .9 6.1 15.1 16.8 21 .2 28.2 33.4 4.4 12.1 12.4 12.8 14.9 16.4 19.3 2.1 l
7 .5 110.0 114.1 122.4 130.B 135.0 6 .0 15.9 17.7 22.5 30.1 35.7 4.8 12.2 12.5 12.9 15.1 16.6 19.7 2.2 !
16.7 18.7 24.0 32.2 38.1 5.2 12.3 12.6 13.1 15.3 16.9 20.1 2.3
8.0 112.6 116.8 125.4 133.9 138.1 6 .2
141 .3 6.8 17.5 19.7 25.5 34.4 40.7 6.4 12.3 12.7 13.2 15.6 17.2 20.5 2.7 I
8.5 115.2 119.6 128.4 137.0
36.7 43.4 6.4 12.4 12.8 13.3 15.8 17.6 21.0 2.7 '
9 .0 117.8 122.4 131 .4 140.2 144.5 6.9 18.5 20.9 27.2
12.5 12.9 13.5 16.1 18.0 21 .4 2.8 l
125.2 134.4 143.3 147.6 6.6 19.5 22.1 29.0 39.3 46.3 6.9
9 .5 120.5
2.9
'
20.7 23.5 31 .0 42.0 49.4 7.7 12.7 13.1 13.7 16.5 18.4 21 .9
10.0 123.3 128.1 137.4 146.4 150.8 7 .B
25.1 33.2 44.B 52.6 8.3 12.8 13.2 13.9 16.8 18.8 22.5 3.1 :
10.5 126.1 130.9 140.4 149.5 153.9 7.3 22.0
47.7 55.9 8.5 13.0 13.4 14.1 17.2 19.3 23.0 3.1 I
11 .0 128.B 133.7 143.3 152.4 156.8 7.9 23.3 26.7 35.4
50.6 59.1 9.1 13.2 13.7 14.4 17.6 19.8 23.6 3.3 I
131.5 136.4 145.9 155.1 159.6 7.1 24.B 28.4 37.6
11 .5
39.8 53.4 62.1 9.0 13.4 13.9 14.7 18.0 20.2 24.1 3.2
134.0 138.9 148.4 157.5 162.0 7.0 26.2 30.0
12.0
31 .6 41 .8 55.8 64.8 9.7 13.7 14.2 15.0 18.4 20.7 24.7 3.3
136.3 141.1 150.5 159.6 164.1 6 .7 27.6
12.5
43.6 57.9 67.1 9.4 13.9 14.4 15.2 18.8 21 .1 25.2 3.2
142.9 152.2 161 .3 165.9 6.9 28.9 33.1
13.0 138.2
34.4 45.1 59.7 69.0 9.8 14.1 14.6 15.5 19.1 21.5 25.6 3.5
139.9 144.5 153.6 162.7 167.2 6.0 30.2
13.5
35.6 46.4 61 .1 70.4 9.6 14.3 14.9 15.7 19.4 21.8 25.9 3.4
145.8 154.7 163.7 168.2 6.6 31 .3
14.0 141 .3
36.6 47.5 62.2 71.4 9.4 14.5 15.1 16.0 19.7 22.0 26.2 3.3
146.8 155.5 164.5 169.0 5.9 32.3
14.5 142.4 3.4
37.5 48.4 62.9 72.1 9.6 14.7 15.2 16.1 19.9 22.3 26.3
147.5 156.1 165.0 169.5 6.6 33.1
15.0 143.3 3.1
38.3 49.1 63.5 72.5 8.7 14.9 15.4 16.3 20.1 22.4 26.4
148.1 156.6 165.3 169.8 5.9 34.0
15.5 144.1 20.3 22.6 26.5 3.1
34.7 39.1 49.7 64.0 72.8 8.7 15.0 15.6 16.5
148.6 156.9 165.6 170.1 6.1
16.0 144.7 22.8 26.6 3.2
35.5 39.8 50.3 64.4 73.1 9.2 15.2 15.8 16.7 20.4
149.1 157.2 165.7 170.2 6.4
16.5 145.2 22.9 26.7 3.0
40.5 50.9 64.7 73.3 8.8 15.4 16.0 16.9 20.6
149.5 157.4 165.9 170.4 6.5 36.2
17.0 145.7 17.1 20.8 23.1 26.7 3.1 I
36.9 41.1 51 .5 65.0 73.4 9.5 15.5 16.1
149.8 157.6 166.0 170.5 6.7
17.5 146.2 17.3 21.0 23.2 26.8 3.6
37.6 41 .8 52.0 65.3 73.5 10.2 15.7 16.3
150.2 157.8 166.1 170.6 6.6
18 .0 146.6 IAP
23rd AE: equivalent to BMI of 23 in adults (overweight); 27th AE equivalent to BMI of 27 in adults (obesity)
N
co
I
• 30
I
age. One time measurement, however, does not indicate, if g
the rate of growth of the child has been normal in the recent should also be monitored.
past. The position on the growth chart becomes evidently
abnormal only when the factors retarding growth are Software and Apps fo Assist Anthropometric Analysl;
profound or have persisted for a long time. On the other for Clinical and Research Use
hand, serial measurements provide rate of growth. Plotting Th WHO rovides software " WHO-Anthro" for anthro-
growth velocity is useful tool for early identification of
factors affecting growth. Velocity of growth more accurately
po~etric a~alysis. The software consists of three mocJul~:
Anthropometric calculator, individual assessment, and
helps in predicting the ultimate adult height.
nutritional survey.
Interpretation ofgrowth measuremeuts:Table 2.11 provides
details regarding interpretation of growth charts for The software is downloadable at http://www.who.int/
children 0 to 5 years of age. childgrowth/software/en/
The page provides the option to download the software
Growth Monitoring WHO-Anthro for personal computers (PC) and mobile
The Indian Academy of Pediatrics has given guidelines to devices. In addition, there are macros for the statistical
monitor growth during childhood (Table 2.12). During software packages to facilitate data analysis.
. .
Table 2.11: Interpretation of growth parameters in children O to 5 years of age
Growth indicators
Z-score Length/height-for-age Weight-for-age Weight-for-length/height BMI-for-age
Above3 See note 1 Obese Obese
Above 2 Overweight Overweight
Above 1 See note 2 Possible risk of overweight Possible risk of overweight
(see note 3) (see note 3)
0 (median)
Below -1
Below -2 Stunted (see note 4) Underweight Wasted Wasted
Below -3 Severely stunted Severely under- Severely wasted Severely wasted
(see note 4) weight (see note 5)
Measurements in the grey shaded boxes are in the normal range
Notes:
1. A child in this range is very tall. Tallness is rarely a problem unless It Is so excessive that it may Indicate an endocrine disorder such as a
growth-hormone producing tumor. Refer a child in this range for assessment, if you suspect an endocrine disorder (e.g. if parents of normal
height have a child who is excessively tall for his or her age).
2. A child whose weight-for-age falls in this range may have growth problem, but this Is better assessed from weight-for-length/height or 81..11·
for-age.
3. A plotted point above 1 shows possible risk. A trend towards the +2 Z-score line shows definite risk.
4. It is possible for a stunted or severely stunted child to become overweight.
s. This is referred to as very low weight in IMCI training modules
r-- ·- - Table 2.12: Suggested growth monitoring in children- at differen t ages-
. Age Height/length Weight Head circumference Other
~~ ~ ~ ~
~ ~ ~
11h, 31h, 6, 9, 15 month s
18 months-3 years ~ (6 monthly) ~ (6 monthly) ~(6 monthly)
3.5-5.5 years ~ (6 monthly) ~ (6 monthly)
6-8 years ~ (6 monthly) ~ (6 monthly) BMI (yearly)
1
, 9-18 years ~ (yearly) ~ (yearly) BMI and SMA (yearfY)
Adapted from guidelines of Indian Academy of Pediatrics (2006)
BMI: Body mass index, SMR: Sexual maturity rating
Growth
I 31 •
I
Growth percentiles Android WHO
Growth chart CDC WHO percentlles Android WHO, CDC
IAP growth charts Android, IOS WHO
. Pediatric growth chart IOS WHO
Pediatric growth charts by Boston Children's Hospital iOS WHO, CDC
STAT growth charts Lite iOS WHO
Child growth chart Windows WHO
Ped (Z) Windows, Android WHO, CDC
The authors provide this list only as examples; they do not endorse these apps. Many other apps are continually being developed, User discretion
Is advised.
Mobile Appllcatlons (Apps) for Analysis of Table 2.14: Causes of short stature
Anthropometric Data
Physlological short stature or normal variant
Several mobile applications (apps) are now available for Familial
instant and quick analysis of anthropometric data Constitutional
(Table 2.13). While a few are paid, many of them are free for
download. Some use the CDC charts while others use WHO Pathological
charts for analysis. A few apps allow users to make choice Undernutrition
of charts for calculations and interpretation. Many of these Chronic systemic illness
apps have additional capabilities and calculators. . Cerebral palsy
Congenital heart disease, cystic fibrosis, asthma
Suggested Reading Malabsorption, e.g. celiac disease, chronic liver disease
• Agarwal DK, Agarwal KN, et al. Physical and sexual grow th Acquired immunodeficiency syndrome, other chronic infections
pattern of affluent Indian children from 5-18 years of age. Indian Endocrine causes
Pediatrics 1992;29:1203-82
• Agarwal DK, Agarwal KN, et al. Physical growth assessment in Growth hormone deficiency, insensitivity
adolescence. Indian Pediatrics 2001;38:1217-35 Hypothyroidism
• Graham CB. Assessment of bone maturation-methods and Cushing syndrome
pitfalls. Radio! Clin North Am 1972,10:185-202 Pseudohypoparathyroidism
• World Health Organisation. http://www.who.int/nut·growthdb/ Precocious or delayed puberty
en. Guidelines on growth monitoring from birth to 18 years Psychosocial dwarfism
Children born small for gestational age
DISORDERS OF GROWTH Skeletal dysplasias, e.g. achondroplasia, rickets
Genetic syndromes, e.g. Turner, Down syndrome
Short Stature
Definition and Epidemiology common etiological factors, followed by growth hom1one
Short stature is defined as height below third centile or deficiency (GHD) and hypothyroidism.
more than 2 standard deviations (SDs) below the median
height for age and gender (<-2 SD) according to the Steps In Assessment
population standard. As is evident from the definition, Accurate heigl1t111eas11reme11t: For children below 2 years,
approximately 3% of children in any given populations supine length should be measured using an infantometer
will be short. Children whose stature is more than 3 SD with a rigid headboard on one side and a moveable
below the population mean for age and gender footboard on the other side, while holding the infant
(<-3 SD) are more likely to be suffering from pathological straight on the horizontal board (Fig. 2.6). For older children,
short stature, as compared to those with stature between height should be measured with a stadiometer, as eA'Plained
-2 and -3 SD, who are more likely to be affected by in previous section (Fig. 2.7).
physiological, i.e. familial or constitutional short stature.
Assessme11t ofl1eigl1t velocihj: Height velocity is the rate of
increase in height over a period of time expressed as
Etiology cm/year. The average height velocity is 25 cm/ yr in the
Short stature can be attributed to many causes (Table 2.14). first year, declines to 4-6 cm/yr in prepubertal children
Undernutrition and chronic systemic illness are the between 4 and 9 years of age and increases during puberty
I 32
-~~~~~~~~~~~~~E~ss~e~n~tl~a~IP~e~d~l~at~rl~c!s------------~-:~::~~::::~:~ the etiology of short stnture
unravel many clues to . vestigative work-up lo bl! done
to a peak height velocity of 10-12 cm/yr. If height velocity
(Tables 2.15 and 2.16). The. ~ y and physicnl examination.
1
is lower than expected for age, the child is likely to be 'd db clues from his or
suffering from a pathological cause of short stature. is gm e Y Id be done in all children with
Bo11c n~e assessment shou of vnrious cpiphyscal ccntcn1
Comparison witl1 pop11lntio11 uorms: The height should ~e
I tc II s nbout th~
'
short stature. Tl le•nppearance '
'ti mctaphyscs
plotted on appropriate growth charts and expressed m f iphyscs w1 1 , i
and fusion o C:P
centile or as standard deviation score. 1 'Id Bone age is convent onnlly
skeletal mntu:1ty of ! ~~ ~ ~ left hand and wrist using either
1
Comp11riso11 witl1 cltild's ow11 geuetic poteutial: Parents' read from rad1ograpl
1 -Whitehouse method. It gives
height significantly affects the child's height. Mid-parental Gruelich-Pyle atlns orTantt~er of the adult height hils been
height (MPH) gives an approximate estimate of the child's 'd t what propor wn ..
an 1 ea as o ' . d h . tis the remammg potcntinl
genetically determined potential. achieved by the child an w a. delayed com P" red to
f h . I t ain Bone age is '
MPH for boys =
Mother+ Father height (cm)
+ 6.5 cm or eig 1. glc · . !most all causes of short stilture.
2 chronolog1ca age in a · h' h b
. th' e familial short stature, m w 1c one
Mother+ Father height (cm) Exceptions to is ar ' ' . b ·
MPH for girls = - 6.5 cm I hron ological age and precocious pu er 1y, in
2 age equa s c ' . I . f
. h b ge exceeds chronolog1ca 1 age. n case o
This value is then plotted on the growth chart at w h ic one a d . 'JI
constitutional delay, undernutrition an systemic i ness,
18-20 years (adult equivalent) of age. This gives an estimate
bone age is less than chronological age and cor:~sponds to
of the target height for the child and the percentile that
height age. In cases of growth hormone def1c1cncy and
he I she is likely to follow.
Assessment of body proportion: Short stature can be pro- · Table 2.15: Clues to etiology of short stature from history
portionate or disproportionate. The proportionality is History Etiology
assessed by upper segment (US): lower segment (LS) ratio Low birth weight Small for gestational age
and comparison of arm span with height. US can be
Polyuria Chronic renal failure, renal
measured by taking the sitting height of the child. Child is
tubular acidosis
made to sit on a square stool placed against the vertical rod
of the stadiometer. The headboard is brought down to the Chronic diarrhea, Malabsorption
vertex similarly as for taking height. The height of the stool greasy stools
is subtracted from the reading obtained to get sitting height. Neonatal hypoglycemia, Hypopituitarism
LS can be obtained by subtracting US from height. jaundice, micropenis
Alternatively, l.S can be measured by taking the length from Headache, vomiting, Pituitary or hypothalamic space
pubic symphysis to the ground while the child is standing visual problem occupying lesion, e.g.
erect. For measuring arm span, child is asked to stand cranlopharyngioma
straight with both arms extended outwards parallel to the Lethargy, constipation, Hypothyroidism
ground. Length between the tips of the middle finger of the weight gain
outstretched hands is the arm span. Inadequate dietary intake Undernutrition
Normally, US: LS ratio is 1.7 at birth, 1.3 at 3years,1.1 by Social history
6years,1by10 years and 0.9 in adults. Increase in US: LS Psychosocial dwarfism
Delayed puberty In
ratio is seen in rickets, achondroplasia and untreated Constitutional delay of growth
parent(s) and puberty
congenital hypothyroidism. Decrease in US : LS ratio is
seen in spondyloepiphyseal dysplasia and vertebral
anomalies. Arm span is shorter than length by 2.5 cm at Table 2.16: Clues to etiolog.y Of short stature from examination
birth, equals height at 11 years and thereafter is slightly Examination finding Etiology
(usually, <1 cm) greater than height. Disproportion Sk 1
e etal dysplasia, rickets,
Sexual mah1rity rntiug(SMR):SMRstage should be assessed hypothyroidism
Dysmorphlsm
in older children (see Chapter 5). Height spurt is seen in early Congenital syndromes
Pallor
puberty in girls and mid-puberty in boys. Precocious puberty Chronic anemia, chronic kidney
ca':1 lead to early height spurt followed by premature disease
ep1physeal fusion and ultimate short stature. On the other Hypertension
Chronic kidney disease
hand, delayed puberty can also present with short stature in Frontal bossing,
Hypopftuitarlsm
adolescents as the height spurt is also delayed. depressed nasal
bridge, crowded
Different/of Diagnosis teeth, small penis
Diagnosis is based on a detailed history, examination and Goiter, coarse skin
Hypothyroidism
laboratory evaluation. Careful history and examination can Cen~ral obesity, striae
Cushing syndrome
-
Growth
I 33 -
------------ -~-
Anterior fontanel ---H.~--\' b
Coronal suture --j~~_;;,,,,jj
Sagittal suture
-----rCr\
Parietal bone
.........
~
Posterior fontanel -~e~r.I
~W
Lambdoid suture 1
a Occipital bone /
g
,ffj
Fig. 2.23: (a) Head of normal neonate showing fontanels and sutures. The common forms of craniosynostosls (secondary to
premature fusion of sutures) Include; (b) Trigonocephaly (metoplc suture); (c) Brachycephaly (bilateral coronal sutures); (d) Left
anterior plaglocephaly (left coronal suture); (e) Scaphocephaly (saglttal suture); (f) Right posterior plaglocephaty (right lambdold
suture). Children with deformation plaglocephaty (g) have positional skull flattening without sutural fusion
Chapter
3
Development
u!trwal • Navecn Sankhyan
Ramush Arr
continuous process of dcvdopmcnt, e.g. turning over, 3-4-month-old squeals loudly and ex~1te y .moves
sitting, rt!nching for objects, nnct pointing to objects. all limbs, whereas a 3-4-year-old may JUSt sffiJJe and
nsk for jt,
While development is n globnl procl'ss reflected in new
motor nbilitfos nnd language, socinl nnu cognitive skills, Factors Affecting Development
lntclllgtmcc pertnins to the port of the development den ling
wiU1 cognitive or ndnptivc behavior. Different researchers Development depends on a varie~ of ~utua~ly i~tera~ve
define intelligence vnrinbly; nn objective mensurcmc1~t is factors such as hereditary potenha], b1olog1cal mtegnty,
done using multiple criterin in tests of intelligence quotient physical nnd psychosocial environment and emotion~)
(IQ). stimu lati on. The brain matures through a dynamic
interplay of genetic, biological and psychosocial factors.
Rules of Development Infancy and early childhood are the most crucia] phases
during which development takes place.
To understand the complex process of human
development, some bnsic facts should be understood: Appropriate sensory inputs through hearing and
vision, a secure environment and responsive parenting
i. Development is n co11ti111w11s process, starti.ng in 11~ero
provide the bases for healthy patterns of learning, behavior
and progressing in an orderly manner until maturity.
and health. Poverty is among the most important risk
TI1e child has to go through many developmental stages
before a milestone is achieved. factors associated with poor development. Poverty
exposes the child to many other risk factors such as lack
ii. Development dt•pe11ds 011 tire f1111ctio11al maturation oft/le
of stimulation or excessive stress, malnutrition, exposure
11N·vo11s system. Mnturity of the central.nervous.system to environmental toxins, and concurrent diseases that
is essential for a child to learn a particular milestone adversely affect development. The factors that influence
or skill· no amount of practice can make a child learn child development are listed below.
new skills in its absence. However, in absence of
practice, the child may be unable to learn skills despite Prenatal Factors
neural maturation.
Genetic. factors : Intelligence of parents has direct
iii. The sequence of attai11ment of milestones is the s~me in all correlation on the IQ of the child. Moreover certain
c1iildm1. All infants babble before they speak m words developmental patterns are observed to follow 'parental
and sit before they stand. Variations may exist in the
patterns like speech. There are numerous genetic causes
time and manner of their attainment. such as chromosomal abnormalities ( Down
iv. The process of dt•velopme11t progresses in a cepltalocau~al syndrome), X-linked mental retardation s~b1~lomeric
direction. Head control precedes trunk control, '"'.h1ch deletions, single gene disorders causing rus'orde f brain
precedes ability to use lower limbs. The control of hmbs formation (lissencephaly) and other metabolic ~~orders
proceeds in a proximal to distal manner, such that hand (phenylketonuria) for developmental delay and
use is learnt before control over fingers. subsequent mental retardation <MR).
38
Development
I J9 -
M11ttr1111/ f1rrlorR1 A host of frlttorf.I which lmpillr growth Early growth faltering (<24 months) seems to be more
/1111/rm nlim c:n11 putc11llnlly nffetl brain growth, partkularJy detrimental to childhood development.
I( lhoy 11tc i;uv1~1'c nnd/ur· HUBlal11cd:
t. M11lm11tl 1111/rl/lr111: Mntcrm1l rnnlnutrltion (of mncro~ lro11 deficiency: Iron deficiency has been shown to be
1111lrhmt l1f1 well ns mlcronulricnts) hns aclvcrs~ effect associated with electrophysiological evidence of delayed
on birth weight nml child ucvclopment. Studies from brain maturation, poorer cognitive, motor and social-
duvcloplng cuu11trlc11 suggcHl lbnt nutrition supple- emotional development in infancy and early childhood.
mc11t1:1 l11clut.ll11g tr1t1lllple mlcrunutricnt supplements Iodine deficiency: Iodine is a constituent of thyroid
hc1vu pos itive Impact on birlh weight as well as child hormones, which affect central nervous system
development. development and regulate many physiological processes.
IL b11m111r1! Iv dr11xo mu/ toxins: Varluus drugs and toxins Iodine deficiency can lead to congenital hypothyroidism
sud1 aH mnlem11I drug or nlcohol abuse, antiepilcptic and irreversible mental retardation, making it the most
tlru~11 1111d cnvlrunmcntnl toxins cun have adverse common preventable cause of mental retardation.
effecl or1 chlld development. Children growing in iodine deficient areas have an IQ 12.5
JJI. Mnlcmul rlir;r·mw11 and it1ft•clio11n: Pregnnncy-induced points lower than those growing in iodine sufficient areas.
hypcrlcnsion, hypothyroidism, malnutrition and feto-
ploccnlal lm1ufflc:iency due lo any cause. Acquired Infectious diseases: A variety of infectious morbidities
infccliom1 (e.g. llyphilis, loxoplasmosis, AIDS, rubella, such as diarrhea, malaria, other parasitic infections and
CMV, hcrpe11) impncl fetal physicCJI and brnin growth. HIV are associated with poorer neurodevelopment.
Exposure lo free rnuicnls nnd oxidCJnts in utero (e.g. Environmental toxins: Children exposed to environmental
chorioamnloniti!l) hag been incriminated in the toxins (lead, arsenic, pesticides, mercury and polycyclic
cawrntion of cerebral palsy and developmental aromatic hydrocarbons) prenatally through maternal
Impairment. exposure and postnataJJy through breast milk, food, water,
house dust, or soil can have adverse influence on their
Neonalol Risk Factors neurocognitive development.
Itrtrtwlcrit1e growtll restrictio11: Intrauterine growth
Acquired insults to brain: Traumatic or infectious insults
restriction (IUGR) indicates constraints in fetal nutrition (meningitis, encephalitis, cerebral malaria) and other
during a crucial period for brain development. In factors (near drowning, trauma), particularly during early
developing countries, JUGR is mainly due to poor years of life, can have a permanent adverse effect on brain
maternal nutrition and infections. IUGR infants are development.
disadvantaged compared to their normal birth weight
counterparts in terms of short-term as well as long-term Associated impairments: Impairments particularly those
neurocognitive development. involving sensory inputs from the eyes or ears can have a
significant impact on attainment of milestones. Early
Prematurity: Babies born before 37 weeks of gestation are
detection and management of hearing and visual
more likely to have developmental impairment compared impairments constitutes an important intervention for
to term counterparts with babies born before 32 weeks promoting child development.
gestation being at the highest risk.
Perinatal asphyxia: Significant asi:'hyxia ~cc~rs in Psychosocial Factors
approximately 2% of total births. Studies have ":1d1cated During the critical period of development and learning,
that over 40% of survivors of significant asphyxia suffer several social factors have an important bearing on not
from major neurocognitive disabilities. only cognition but also attitudes, social-emotional
competence and sensorimotor development.
Postneonatol Factors
Parenting: Cognitive stimulation, caregiver's sensitivity
lnfant and child nutrition: Severe calorie deficiency, as and affection (emotional warmth or rejection of child) and
evident by stunting, is associated with apathy, ~epressed responsiveness to the child in the setting of other factors
.
affec t , d ecrease d play and activities and· insecured ·h such as poverty, cultural values and practices have an
attachment. Calorie deficiency is often ass~c1at: wit important bearing on child development. Apart from
. .
d ef1c1ency o f mu It.1ple m.1·cronutrients and vitamins that these, parental attitudes, involvement, education and
contribute to developmental impairment. . desire for the child also have an impact on the develop-
Linear growth retardation or stunting o~curs ~nearly ment of the child.
one-third of children aged less than 5 year~ ~n low-m.co~e
and m1'ddle_.income countries. There is positive association Poverty: This is possibly the most common underlying/actor
Tve or langua<>"e for impaired child development worldwide. It acts
between early height-for-age and cogru 1 • o
ab1'J.'1ty, rates o f sch oo1 enrolment and grades attamed
0- by throughout the lifetime of the individual and also affects
late adolescence and formal employment at age 2 22 years. the next generation.
• 40
~~~~~~~~~~~~~lE~s~s~e~nt~la~l~P~e~d~la~t~rl~c!s_______________________~~-------......
f Development
Lack of stim11latio11: Social and emotional deprivation and Domains o . ornplex process and has a
ent 1s a c ·
lack of adequate interaction and stimulation is an Normal deve1oprn r it is converuent to under.
important cause of developmental impairment, multitude of facets. Howev~~der the following domains.
particularly evident in the setting of poverty. tand and assess developmen .
s i Gross motor d eve1o pment
Violence aud abuse: Domestic and community violence . kill development
are emerging threats to child development. Child abuse, ii. Fine motor 5 . development and general
physical and sexual, can have a profo~d psycholo~cal iii. Personal and socla1
Protective Factors
Breastfeediug: Breastfeeding has a protective and
promotive effect on childhood development.
Maternal education: Maternal education is a protective
factor reducing child mortality and promoting early child
development. Infant and young children of educated
mothers have higher levels of cognitive development.
t
Risk factors > protective factors
'
fig. 3.5: Ventral suspension; unable to hold neck In the One With Ag. 3. 9: The infant Iles wrn fl01 oei.·:s cno e o 31'l090 ..1a ~
trunk at 4 weeks 6 w~s (Photo courtesy: Dr Vi}C'V K Cha:cri)
Essential Pediatrics -
~~--~~~~~~~=...:_.::;::::;---
..
- 44
3~
smomhS
6 mon1hS
s morons
g months
12 monthS
15 months
18 moothS
2years
' .
3 years
.
;
1-·-·
,. ..! 4 years
Fig. 3.21: Stands independently at 12 months
Ffrie MotOf SkiJ [)eVe[Opm911f
This primarily involves ~e ~evel?pment of fo:r
manipulation skills and coordination w1th age.
Hand eye coordination: Between 12 and 20 wee..\:s., fut
child obsen-es his O\'l."TI hands very intently, this is cill:-.5
hand regard (Fig. 324). Its ~-istence after 10 we.:.~ is
considered abnormal. At 3 to 4 months, hands of the u\:lJ
come together in midline as he plays (Fig. 325). lf a rej
ring is dangled in front of him, he fixes his attention cm :.t.
and then tries to reach for it (Fig. 326). Initially, he m.:.y
o\·ershoot but eYentually he gets it and brings it to illi
mouth.
Grasp is best as..~ by offering a red cube to the ol.j)d.
A 6-month-old infant reaches and holds the cul-e {b.rg?
object) in a crude manner usincr the ulnar asf'C'l-'i: of r~
hand (Fig. 3_27). He can transfer~bjects from one h.md t::i
oth~ by 6-1 months. The child is able to grasp from the
radial side of hand at 8-9 months (Fig. 328). B\· the ab'"ci
1 year, mature grasp (index finuer0
and thumb) is e,iJo.t
Ag. 3.22: Child walking with one hand-held at 12- 13 months (Fig. 3.29).
By offering pellets (smaller object), finer hand skills;.:~
assessed. By 9-10 months, the child approaches the peJJr?!
- --- -· -·-_..... .. _ -- -"r--- - . - -
Ag. 3.23: The child Is able to walk upstairs and downstairs one
foot per step at 4 years Ag. 3 ·24: Hand regard (between 12 and 20 wee!..'S)
rt'I
I 45 •
I
Fig. 3.28: Intermediate grasp at 8 months, beginning to use
radial aspect of the hand
Fig. 3.29: Mature grasp at l year of age, note the use of thumb
and Index finger
I
Fig. 3.31 : A Child moUihlng an object at 6 months of age
6 ~ 0
5 years 6 years 7 years
anyone talks to him or smiles at him by 6-8 weeks of agf
(Fig. 3.38). Itis important to differentiate sodalsmileoom
spontaneous smile (smile V\rJthout any social interaclicm),
which is present even in neonates. By 3 monfhs, he enjoy3
looking around and recognizes his mnther. By 6 months,
I
0 D CD
he vocalizes and smiles at his mirror image (Fig. 339),
and imitates acts such as cough or tongue proirusion.
The child becomes anxious on meeting strange;rs
(stranger anxiety) by 6-7 months of age. At this ,age, he
8 years 9 years 11 years inhibits to "no". At 9 months, he v;an~s !>ye-bye"' and
also repeats any performance that evokes an a;ppredaID-e
Fig. 3.35: Drawing skills at various ages response from the observers. By 1 year,, he can understand
15 months 18 months
(tower of 2 blocks) (tower of 3 blocks) 2 years (train)
I
comes w h en C '
12 months
15 months Jargon .
Copies parents in task (~.g. sweeping)
18 months
drink toilet; pulls people to
2 years Asks for food • '
show toys
Shares toys; knows full name and gender
3 years
Plays cooperatively in a group; goes to toilet
Fig. 3.37: At l month. the baby showing intent regard of his
4 years
alone
mother's face as she talks to him
Helps in household tasks, dresses and
5 years
undresses
Language
Throughout the development of language it is the receptive
ability and 1111dersta11ding, which precedes expressive abilities.
Soon after appearance of social smile at around 6 to 8
Fig. 3.38: Social smile weeks, the child begins to vocalize with vowel sounds
such as 'ah, uh'. At 3-4 months, he squeals with delight
and laughs loud. He begins to say 'ah-goo', 'gaga' by 5
?
months of age. By ~nonths, he uses monosyllables (ba,
da, pa). Later, he ioms consonants to form bisyllables
(mama, baba, dada).
Before developin~ true meaningful speech, at around
9-10 months, the duld learns to imitate sounds derived
from his native language. At his first birthday, he can
usually say 1-2 words with meaning. At 18 months, he
has a vocabulary of 8-10 words. Thereafter the vocabulary
inc~·eas~s rapidly to aro~u1d 100 words' by 2 years, at
which tune 2-3 words are Joined to form simple sentences.
By 3 yen~·s, .the toddler continually asks questions and
knows lus tull .name. He can give a coherent account
Fig. 3.39: A child smiles at hlmself In the mirror at 6 months of of recent expenences and events by the age of 4 years
age (Table 3.4).
Development I 49 ..
I
9 months Blsyllables (mama, baba, dada)
12 months 1-2 words with meaning
18 months 8-10 word vocabulary
2 years 2-3 word sentences, uses pronouns" I", "me",
"you"
3 years Asks questions; knows full name and gender
4 years Says song or poem; tells stories
5 years Asks meaning of words
Developmental Assessment
Developmental dl'lay is estimated to be present in about
10% of children. It is possible to recognize severe develop-
mental disorders c«rly in infancy. Speech impairment,
hyperactivity and emotional disturbances arc often not
Fig. 3. 4 o: Infant fixates on her mother as she talks to her at detected until the child is 3-l·year-old. Leaming disabilities
l month are not picked up until the child starts schooling.
50 ~~~~~~~~~~~~~~E!ss~e~n~t~la~l!P~e~d~la~t~rl=cs:!...-----~~----------~~~~--~---....
l ua tion' one should be able to
Prerequisites By the en d o f .the eva th · l s ta tus and
r the neuro logica
The development assessment should be assessed in a arrive at a conclusion whe e.-.<>I range or not. Significant
within no....... ·1
place, which is free from distractions. It is important that cognitive status ~re . an indication for a detai ed fonna1
the child should not be hungry, tired, ill or irritated at delay on screerung is ment status. By assessment, one can
time of development assessment. It would be desirable to assessment of develop tient (DQ) for any develop-
assign developmenta 1 quo .
assess him when he is in a playful mood with mother being
around. Adequate time should be spent in making the mental sphere. It is calculated a~. ent
child and family comfortable. Observation for alertness, Average age at attamm xlOO
· ent
Observed age at attauun
concentration and skills of the child is an integral part of
assessment. The assessors must carry a development kit ak delay and warrants detailed
A DQ below 70%. is t en;:a child, a formal assessment
(Box 3.1).
evaluation. To obt~ a ~d lopmentalassessmentusing
. di .d al tramedm eve
b y an m
Steps vi u . d d There are several tests
appropriate tools/t~~t~a~ ~e~~ ~sychometric properties.
Histonp A detailed history is the starting point for any to assess DQ. Each . f tim tes of development like
development assessment. Observations by parents are The ·ve different kinds o es a
very informative. Hence, a well-taken history will help in Y gi score of d evelopment and subscores
an overall ti 1for grOSs
(i) determining the details of probable risk factors affecting motor, fine motor, visual perception, recep ve anguage,
development, (ii) evaluation of rate of acquisition of skills expressive language, etc. . .
and differentiating between delay and regression, and (iii) IQ tests mainly assess the cognitive/ ad~ptive be~vior
forming a gross impression about the development age part of the development. The age at wi:uch a particular
of the child. This helps to choose the appropriate tools for test can be applied depends on the test items. i:owever,
further evaluation and confirmation. in younger children (<5 years): ~t. is more mearun~ ~o
Examination: This should be done to (i) assess physical have a global assessment of abilities; hence DQ testin.g IS
growth and head circumference, (ii) do a physical more comprehensive. Specific IQ tests (Stanfo.rd-Bmet
assessment particularly for presence of dysmorphic intelligence scales) are available to asses IQ starting from
features, stigmata of intrauterine infections and signs of 2 years of age.
hypothyroidism, (iii) assess vision and hearing, and (iv)
conduct neurological examination and examine for Interpretation
primitive reflexes (if required). In babies born preterrn, corrected age rather than postnatal
Adequate time should be spent in observing the baby age is used for determining developmental status till
especially social responsiveness, alertness, concentration, 2 years of age. For example, a child born at 32 weeks gesta-
interest and distractibility. It would be appropriate to tion (gestational age) seen at 12 weeks of age (postnatal
assess vision and hearing at the outset so that further age) should be considered as a 4-week-old (corrected age)
observations are not confounded by lack of sensory child for developmental assessment.
stimuli. The vocal responses, particularly the nature, While drawing any conclusions about development,
frequency and quality are noted. Subsequently, fine motor one should remember the wide variations in normality.
skills should be assessed, including the interest, alertness For example, let us consider the milestone of standing
and rapidity of responses. alone. The average age for attainment of this milestone in
The annoying maneuvers, such as assessment. of a WHO survey was 10.8 months (Fig. 3.43). However, the
reflexes, measuring head circumference, and performing 3rd and 97th centiles for normal children were 7.7 and
ventral suspension or pull to sit should be done at the 15.2 months, respectively. The same is true for many other
end. It is preferable to perform the developmental milestones as is shown in Fig. 3.43. The bars illustrate the
assessment before the systemic examination so that the age range for normal children to attain that particular
child's cooperation is solicited. milestone. This range of normalcy should always be kept
in mind while assessing development.
Box 3. l: Equipment for development assessment
~etardation should not be diagnosed or suggested on
c • A red ring (diameter 6-7 cm) tied to a string
a single feature. Repeat examination is desirable in any
I • Nine red cubes
child w~o does n?t ~a~e a gross delay. Factors such as
, • Paper pellets ·
recent illness, s1gmhcant malnutrition emoti nal
: •Spoon , ·
deprivation, slow maturation, sensory deficits and
~ • clip with handle
neuromuscular disorders should be taken into account.
· • A _bookwith thick pages
At times, there can be significant variations in
• Picture book '
attainment of milestones in individual fields this is called
• Red penc:il, paper , ·-r. ...
• Doll and.mirror .', _ ~-: :-l.,_ - · .... !l.: , _
dissociation. ~or exa~ple, a 1-year-old childwho spe.lks
......,._!A... ·-· 2-3 words with mearung and has finger thumb opposition
Development I s1 •
_________ .. _ _ l4t
r. ·- -·-- -· - Walklng
- . olono
. . 1
, -~-+
L - --·~ -
CD
_§ ----·· H WalklnQ-~lth as~stanc-; ~-·
-- -
+--
iIs r-
' '1) -- - H Hands and knees crawling
:t
- - - 1-l
I
Fig. 3.43: Windows of achievement of six ma]or motor mllestones (WHO; Multlcenter Growth Reference Study Group, 2006)
(10-12 months), may not be able to stand with support Development Screening Tests
(less than 10 months). Such children require evaluation Screening is a brief assessment procedure designed to
for physical disorder affecting a particular domain of identify children who should receive more intensive
development. A child having normal development in all diagnosis or assessment. Screening tools are standardized
domains except language may have hearing deficit. instruments to evaluate development. The administration
Table 3.5 gives the upper limits by which a milestone of these tools should be done after proper training and
must be attained. A child who does not attain the milestone with a sound knowledge of interpretation of the results.
by the recommended limit should be evaluated for cause Some tools are parent reported while others require
of developmental delay. trained personnel. Assessment using screening tools
The predictive value of different domains of devel?p- potentially aids in early identification of children who
ment for subsequent intelligence is not the same. Fme need a more detailed assessment and possibly interven-
motor, personal-social and linguistic milestones predict tions. It also provides an opportunity for early identifica-
intelligence far better than gross motor skills. In particular, tion of comorbid developmental disabilities.
an advanced language predicts high intelligence in a
child. Developmental Survelllance
,. - ·-- -- - .. . .. ........... Child development is a dynamic process and difficult to
Table-3.5: -Upper limit of age for attainme~t of mllestone .
quantitate by one-time assessment. During surveillance,
. Milestone Age repeated observations on development are made by a
· Visual fixation or following 2 months skilled physician over time to see the rate and pattern of
Vocalization 6 months development. Periodic screening helps to detect emerging
Sitting without support 10 months disabilities. The physician should choose a standardized
Standing with assistance 12 months developmental screening tool that is practical and easy to
14 months use in office setting. Once skilled with the tool, it can be
Hands and knees crawling
used as screening method to identify at risk children.
Standing alone 17 months
Screening tests popular in the west include Parents'
Walking alone 18 months Evaluations of Development Status (PEDS) and Ages and
· Single words 18 months Stages Questionnaires (ASQ). Screening tools used in India
Imaginative play 3 years are described below.
Loss of comprehension, single words or phrases at any age · Pita ta k 's Baroda scree11i11g test: This is India's best known
Adapted from WHO; MGRS group, WHO motor development study. Acta development testing system that was developed by J?r.
Pediatr 2006;450:86-95 Promila Phatak. It is meant to be used by child
- 52
psychologists rather than physicians. It is the Indian Definitive Tests ~ng tests or cl;_-: _.
· ed once scr~·~ ·. . . .:v..
adaptation of Bayley development scale and is applied to These tests ~e req~I They are pnmanly ax~ ~
children up to 30 months. It requires several testing tools assessment is _abno . · airJilents in both ciegree a-~
and objects that are arranged according to age. The kit is accurately define the;x1Rving scares for verb.al, ~:~
available commercially. sphere. For example, Y gtnaJ and social skills, ~ ~
Ages a1td stages questionnaire (ASQ-3): It consists of age- mance abili~es and P~ Some of the common sea~
based, parent-completed questionnaires that can be used be differentially quan ·
IJ
used are detailed in Table 3.6.
from one month to 5lh years of age. It assesses the
following domains: Communication, gross motor, fine
motor, problem solving, and personal-social. There are Early Stimulation . of .l--~ ..
- .__..,....+o.1 or early S1grt5 UC'> .......,r::r:e-~
about 30 items per questionnaire about the child's abilities. InfantswhoshowsU!>r":....- ortunities that pnr--J:t.,.
The questionnaire takes about 10-15 minutes for parents delay need to be provided opp kills Lan ·
to complete and about 2-3 minutes to score. body control, acquisition ~f motor-~~ Jhese [¥
Denver II: The revised Denver development screening test
development and psychosoaal matun · ~·
. ulation include measures stu:." l a:?
1
terme d ear y s tun ' • ... -~
(DDST) or Denver II was revised in 1992 and assesses child . ddi . na1 £forts to make the chila Slt or .,.,., ~
development in four domains, i.e. gross motor, fine motor
adaptive, language and personal-social behavior, which
making a tio e . ~ :1d 1!..- -
giving toys to manipulate, pla}ingw1:th the u w_ ,
objects, speaking to the child and _encoura~c ~ :J
,-? :w:.
are presented as age norms, just like physical growth curves. speak and prompting the child to mteract 'nth cra-.e::.
Trivandnmi development screen ing clzart: This screener etc. r • -
has been revised in 2013. It consists of 51 items for children There is a general lack of ectdence _for e~em:5E er
of ~ years. The norms have been adapted from various these early interventions in improvmg neurooe:~
existing developmental charts/ scales. It is primarily a mental outcome and motor abilities. However, stu,,. ~ r::
screening tool for use in the community to identify premature babies, cerebral ?alsr, institutionalize:
children between 0 and 6 years with developmental delay. children and other children at high nsk for adYa5e m::•- ---
Clinical adaptive test and clinical linguistic and auditon; developmental outcomes suggest that these ~
milestone scale (CAT/CLAMS): This easy to learn scale are effective, if started early. Systematic revie\t.;s su~ct
can be used to assess the child's cognitive and language that the effect of these interventions is s ustained in f~
skills. It uses parental report and direct testing of the childhood.
child's skills. It is used at ages of 0-36 months and takes
10-20 min to apply. Promoting Development by Effective Parenting
Goode11011glz-Harris drawing test: This simple nonverbal Comprehensiv e care to children r equir es f°'-""US Cl::
intelligence test requires only a pencil or pen and white preventive efforts including child-rearing infoIII12.ti<D :JI
unlined paper. Here the child is asked to draw a man in parents. Parenting has an immense impact on emo::;J:.;!...
the best possible manner and points are given for each social and cogniti\"e development and aL'O plays a !Ct~:::
detail that the child draws. One can determine the mental the later occurrence of mental illness, educational b1~
age by comparing scores obtained with normative sample. and criminal beha,;or. Creating the right conditi :.s :::r
f •• --
~ - .... -
Table 3.6: Scales for definitive testing of intellect and neurodevelopment
; Name of the test Age range Time taken to administer Scoring details; ~"rs
Bayley scale for infant 1 months to 30-60 min Assesses language. behavior. fine mo:---
development II 3.5 years gross motor and problem-sotving ~
provides mental de\"el<>pment inda'< a.'10
psychomotor developmental index
Wechsler intelligence 6 to 17 years 6~0 min Ass~sses verbal and perlormance s! ,,..,
scale for children IV provides full scale IQ and indices cl \:e:::'..::..
com~rehension perceptuaJ rea~"t!ng~
working memory and Processing ~.::
' Stanford-Binet intelligence 2 to 85 years 50-60 min Provides full scale IQ, verbaJ IQ. nomo:?r!' ~
• scales, 5th edition IQ, 10 subset scores and 4 com..."'OSi!e ~.:_-2:.
Vineland adaptive o to 89 years 2o-60 min Measures personal and social s..~ as
behavior scale 11 report~ by the caregiver or parent. in
4 domams (communica.~- ~""'''" .,.,.
. ""''· ~>' i.•"U1'9
skills~ soaafization and motor S! .
Development 1 sa I
early childhood development is likely to be more effective
8
and less costly than addressing problems at a later age.
I
~ead, and . also limits creativity. Children can pick up
mappropnate. lan~age and habits by watching TV shows
and commercials. Violence and sexuality on television can
have a lasting impact on the child's mind. Parents need to
r~g~~ate bot~ the quantity and quality of TV viewing,
hnuting the time to 1-2 hours per day and ensuring that
the content they see is useful.
Developmental and
Behavioral Disorders
Biswaroop Chakrabarty • Sheffali Gulati
The cognitive growth and behavioral phenotype of an start walking from sitting and standing without support.
individual chiefly reflect the growth and development of Dissociation is defined as the acquisition of develoi:mental
• the body, particularly the brain, during early years. Factors milestones in various domains at differing rates, e.g. isolated
like nutrition, environment and social and emotional speech delay with normal development in other spheres,
milieu play a significant role. as in patients with congenital hearing loss.
Etiology
GLOBAL DEVELOPMENTAL DELAY, INTELLECTUAL DISABILITY
An etiology can be defined in 70% patients with
Global developmental delay is defined as delay in developmental disorders (Table 4.1). In developed
acquiring milestones in two or more of the following countries, antenatal factors predominate; whereas in the
domains, namely gross and fine motor, speech and developing world, perinatal and postnatal factors are more
language, cognition, socio-personal and activities of daily common. Patients with developmental delay may have
living. Above 5 years of age, the term intellectual disability various comorbidities depending on the etiology
is used, replacing the previously used term mental (Table 4.2). Depending on the etiology, the yield of
retardation. The estimated prevalence varies between 2.5 diagnostic tests varies from 10 to 80% (Table 4.3).
and5%.
Management
Developmental Deviance and Dissociation A child with developmental delay is managed by a
Deviance is the acquisition of milestones in a sequence that multidisciplinary team comprising of a pediatric neurologist,
is different from usual. For example, children with cerebral geneticist, psychologist, psychiatrist, occupational and
palsy may show early standing with support secondary to physiotherapist, speech therapist, audiologist, ophthalmo-
increased extensor tone. This may also be seen in normally logist, nutritionist and social worker. Early intervention is
developing children; children may not crawl and directly important to achieve the maximum potential
/ .
! -~.- ·-~.':··~- '.. -I ·i&bii 4:1: Etiology of de;eiOp~-~ntal delay acc"C;~cii~g-to' the t ime ~·insult r --· ,~~ - , • .... r· ··1
'Antenatal
-. Syndromes (fragile X, Rett syndrome)
Chromosomal disorders (Down syndrome)
Cortical malformations
Intrauterine infections
Inborn errors of metabolism (aminoacidopathy, organic acidemia, mitochondrial disorder u
disorder, disorders of glycosylation) • rea eye1e
Teratogen exposure
Neuromuscular disorders (predominantly motor delay)
Perinatal, neonatal Hypoxic ischemic encephalopathy
Kernicterus
After meningitis or encephalitis
Hypoglycemic brain injury_
Hypothyroidism
...
.l~
54
- 4
Dovolopmontol ond Bohnvlornl Disorders
Electrophyslologlcal tests Where Indicated: Electroencephalogram, visual evoked responses, bralnstem evoked :
response, audiometry, nerve conduction studies, electromyography · '. _. . ., .~ -·~ ._.; ! 1
MRI: Magnetic resonance Imaging: GCMS: Gas chromatography mass spectrophotometry; TMS: Tandem mass-spectrophotometry - - ~
. . .- -.
I
., . - .....
....-
56 ~~~~~~~~~~~~~~E!ss~e~n~t~la~l£P~e~d~la~tr~lc~s~----------------~~-=~-=~-----..._
. . . 'fie learning disability . ·1
Table 4.4: Clinical features of autism, ADHD and speci
Disorder Salient clinical features
Autism spectrum disorder Onset before 3 years of age
Impaired verbal and gestural communication
Defect in social and emotional reciprocity
Stereotypic and restrictive behavioural patterns
Attention deficit hyperactivity Onset up to 12 years of age
disorder (ADHD) Present in at least 2 different social settings r ing
Interfering with social, academic and occupational fun~ ion mistakes, easily distracted)
Inattention (difficulty sustaining attention, prone to care ess
Hyperactivity (often on the go, fidgety)
lmpulsivity (intrusive, interruptive, cannot wait for turn)
Specific learning disability• Dyslexia (difficulty in reading)
Dysgraphia (illegible handwriting, spelling mistakes)
Dyscalculia (difficulty performing simple calculations)
"Preserved Intelligence, vision and hearing
Persistent for at least 6 months despite interventions targeting specific disability
or vocal manifestati hi
ons w ch may be simple or complex
-- ·- :r;i>,;-i.5;-cof!Jmon-ti~-i;chi1ci~~~---:-- --- - --~- - -:·-~---~--::-. .-~~;;:-'.
Motor tics
•
Vocal tics
..
·
••• ~ ' ·,..:. 'it-
. '-'··:. ·~-t! ,,,-n_i:;
' ' '" .: , ~.... ~ •'
· - ~, ~-,
1
• •• • - # J.• .. ~.-· .:
' •'(, -~ .... 1· ·' ,1
Simpie Simple . -. _ ,t ·· - ~,;;;~- :.,.JI .._::.-..
Eye blinking, neck jerking, shoulder shrugging Throat clearing, sniffing, coughin , ~, ~ .' :· . ·...' '.· .. -~'
Complex Complex .g . · :- ,:. » '-' · ... 1
••
: Foot tapping, echopraxia (imitating others), copropraxia Words out of context c~prolar ' ... : . . '-· ._, ,· ~-·· .. , . .. :1·. . - .
(obscene gestures) (repeating heard phr~ses or la (obscene words), echolalia ; .....
or phrases) .. ,. ,. . )YOrds), palilalia (repeating own words
• ' .:.;. _. ; ':-.1.: v ':-~.:;- .. ,. ' .. , • . • ·,_,_;.:.,_,. :.'. • . •. -~,,_:. ''\. ...y !
·.·
Developmental and Behavioral Disorders
I s1 -
(f:iblc 4.6). The a 0 f .
)·curs 'and s 1·gn1"f~e onset is 4-6 years with peak at 10-12
leant attenua rion b y 18-20 years. Th e
delay, psychosocial stress (maternal deprivation, parental
pr~valence is neglect and abuse) and other behavioral disorders can
around 10-15% with higher rate in boys. predispose to pica. Children with pica are at increased
Tourette syndr .
18 )"l.'ars of a e ome is characterized by onset before risk for lead poisoning and parasitic infestations.
. t g ' presence of both motor and vocal tics and Management comprises behavior modification, alleviating
p1o•1-s1s ence beyond 1 . .
c.m be associated . year, md~dmg the waning phase. Tics the psychosocial stress, screening for lead poisoning,
. . WI th neurological ailments like Huntington deworming and iron supplementation.
;m d W i1son disease o . th . . .
t>diatric aut . ' r wi parainfectious illnesses, e.g.
P
I
0 unmuneneurops chi tr" dis d · d
with strcpt . . Y a ic or ers assoaate Temper Tantrums
. . ococca1 infection (PANDAS).
Temper tantrums are a child's response to physical or
lt is 111'Portant to differentiate stereotypies from tics.
Alth oug 11 stereotypi emotional challenges by attention seeking tactics like
.f . es may h ave Slffillar
. . vocal and motor
yelling, biting, crying, kicking, pushing, throwing objects, I
ma . ni estations l ·
' c assica 11 y they are rhythmic and hitting and head banging. Tantrums typically begin at
dts t.rkact~ble, and usually remain stable over a time period
1
un 1 e hes which may evo1ve temporally. Stereotypies' 18-36 months of age and gradually subside by the age of
3-6 years. Parents are counseled to handle this behavioral
usua 11 Y ~ave an early onset (before 3 years of age) and problem strategically, by staying calm, firm and consistent
along wit~ neurodevelopmental disorders, may affec~ so that the child is unable to take advantage from such
normal cluldren, as well.
behavior. The child should be protected from injuring
himself or others. Distraction and 'time out' techniques are
Management
useful.
The . es~enti~l component is behavioral therapy.
Medications hke haloperidol and clonidine are considered Breath-Holding Spells
i~ situ_ations w.here the tics are socially and functionally Breath-holding spells are reflex events typically initiated
d1sablmg despite adequate behavioral therapy. by a provocation that causes anger, frustration or pain
making the child cry. The crying stops at full expiration,
Eating Disorders and the child becomes apneic and cyanotic or pale. In
This group consists of primarily two disorders, anorexia some cases, the child may become unconscious and
nervosa and bulimia that chiefly affect girls and have in hypotonic. In prolonged events, brief tonic-clonic
common a disturbed body image perception. Anorexia movements may happen. Breath-holding spells are rare
nervosa usually affects 15--19 years old girls. Characteristic before 6 months of age, peak at 2 years and abate by
features are an intense fear of becoming fat even though 5 years of age. The differential diagnoses include seizures
the child is underweight, with body weight <85% of and cardiac arrhythmias. The history of a provoking
expected. Two subtypes are recognised, with either event and stereotyped pattern of events help in
restricted eating or increased physical activity. Induced distinguishing breath-holding spells from seizures. In
vomiting or use of laxatives and diuretics may be present. relevant clinical scenarios, seizures and cardiac
Complications include secondary amenorrhea and arrhythmias including long QT syndrome should be
metabolic complications related to malnutrition. ruled out.
Bulimia affects 10-19 years old children, chiefly girls. The essential component of management is parental
There are recurrent episodes of binge eating alternating reassurance. The family should be advised to be consistent
with inappropriate compensatory behavior such as self- in handling the child, to remain calm during the event,
ind uced vomiting, misuse of laxatives, diuretics or turn him sideways so that secretions can drain and avoid
enemas, each occurring at least twice a week for 3 months. picking the child up (since this decreases blood flow to
Depression, anxiety, suicidal ideation and/ or obsessive the brain). The family should avoid exhibiting undue
compulsive disorder are often present. Management of concern nor give into the child's demands, if the spell was
both conditions focuses on psychotherapy, along with provoked by anger or frustration.
nutritional rehabilitation and treating comorbidities and
Thumb Sucking
complications.
This entity is normal in infants and toddlers. It peaks by
Pica 18-21 months of age and usually disappears by the age of
Pica is the persistent ingestion of non-nutritive substances 4 years. Its persistence in older children is socially
such as plaster, charco~l, ~aint and soil for at least 1 month, unacceptable and can lead to dental malaligrunent. In
inappropriate to the chl!d s ~evelopment level and cultural children below 4 years, parents should be reassured.
practice. It is commo~ m children less th~ _5 years of.age. Beyond 4 years of age, the child should be motivated
Poor socioeconomic status, malnutrition and iron to refrain from this habit. Both positive 'and negative
deficiency are commonly associated. Developmental reinforcements can be used.
58
'•~I -
... ._ I ~ '
5
Adolescent Health and
Development
Tushar R Godbole • Vijayalakshmi Bhati~
l
Appearance of breast bud
Sparse straight hair along the labia
·~·
_________________ ______
Fig. 5.1: Sexual maturity rating (l-5) In girls (Courtesy: Anll Kumar. Sanjay Gandhi Postgraduate Institute of M"""'ical Selene -
· · "'"' _ es. Lucknow)
60 '
,.
......,....... -..:__: ....-
- Adolescent Health and Development
Th b cmg to -9 years m many popu1ahons. muscle mass and bone diameter, particularly in boys and
e reast buds may be tender and there may be total bone mass in both the sexes. Lean body mass
as~mmetry in the breast size during early phases of increases during the early stages in both the sexes, fat mass
pthulerthy. Menarche usually occurs after 2-21h years of increases in girls at later stages of puberty. Under the
e arc e.
influence of sex steroids, rapid calcium accretion occurs
In boys, the earliest change is increase in testicular size during puberty, achieving almost 50% of adult bone mass.
(volume reaching 4 mL or length 2.5 cm) that occurs The recommended dietary allowance (RDA) for calcium
between 9 and 14 years (Fig. 5.2). This is followed by is 800 mg/ day and an intake of 500 mL milk is
appearance of pub·ic h air · and lengthemng. of the perus. . recommended in order to achieve this with a cereal-based
Spermarche or production of sperms starts during mid- Indian diet. With minimal sun exposure, the RDA for
I
adolescence Lar .
. · yngea 1 growth under androgenic vitamin Dis 600 IV I day. Since dietary vitamin Dis mainly
st~mulus, m~nifesting as cracking of voice, begins in available from fatty fish, intake as a pharmacological
rmdpuberty m males and deepening of voice is complete supplement may be necessary. Increase in body structure
~y the ~nd of puberty. Mild degree of breast enlargement is paralleled by increase in blood volume and muscle mass;
is se~n m more than half of boys in early puberty which both of these tissues have high iron content. With
subsides spontaneously over several months. The onset commencement of menstruation, nutritional requirements
of puberty is variable; thus in an age cohort (e.g. students of iron are further increased. With predominantly cereal-
of 7th cl~ss), many will have advanced puberty while based diet and poor bioavailability, an adolescent needs
others will be awaiting its onset. to have a daily intake of 25-30 mg iron in order to meet
the daily requirements of 1.3 mg.
Physical Growth and Nutritional Requirements
During puberty, boys gain about 20-30 cm and girls about Cognitive and Social Development
16-28 cm. Peak growth velocity in girls occurs before Volumetric and functional imaging techniques show that
attainment of menarche (stage 3), while boys show peak the adolescent brain undergoes subtle structural changes
growth velocity during later stages of puberty (stages 4-5). and differential growth. Though the exact implications of
The growth spurt affects the distal skeleton first, hence these changes are largely unknown, these indicate re-
enlargement of limbs and extremities is followed by organizational or accommodating effort of brain
t~n Prepubertal
<3 ml 3
4ml
!~
~
Reddening of scrotum , testicular volume reaching 4 ml or length 2.5 cm
Scanty hair at penile base
!~
Increase in length of penile shaft
Further increase in testicular volume
Hair begin to curl and darken
3
10ml
. '
~
·
25mL
.t :. ' .••
Fig. 5.2: Sexual maturity rating (l-5) In boys (Courtesy: Anll Kumar, Sanjay Gandhi Postgraduate lnstlMe of Medical Sciences, Lucknow).
·.# • . .;
62 ~~~~~~~~~~~~~E!ss~e~n~tl~a~l~Pe~d~l~at~rl~c!s~~~~----------~--~~~---~
. anemic; the prevalence of
p aralleling the multi-fold increase in its functional 53% Indian adolescent girls are d over the last two
cap.1bilities. anemia has remained unchange sure due to clothing
decades. There is lack. of :un exf ~nsufficient intake of
E1trly p lw~;r: The 'concrete thinking model' of childhood
coupled with dark skin pigmen: t ke of calcium and
persists into early adolescence, where the concepts are t · poor ma
dairy products resu l s m b mineral density is
perceived more 'literally'. Teens are impulsive and have . . B Th lting low one
limit ~d ability to pcrcdve future implications of their
v1tamm 12· e resu . . d girls as they have
more pronounced in underpnvt1ege . d ·t · D
current behavior . They prefer same sex peers. Many are . . . dition to calcium an v1 amm
low protem mtake m ad . . . an important issue
excessively conscious of other people's concerns about . ·
d e f1c1ency. v·t · A deflClency is a1so
1 amm t Undernutrition
their appearance and actions. Curiosity about sexual
in economically deprived adolesc:~ :~xual maturation,
anatomy and comp;nison with peers is common. often delays the onset of puberty a al and reduced
l . . r bone mass accru
Mid-pl111st':This phase is marked by emotional autonomy; resu ts 111 stunting, poo f T are likely to suffer
th ey might seem detached from their family. The youth work capacity. Girls from poor am~.1es . . ation in food
from malnutrition due to gender iscnmm .
starts to think beyond self and there is beginning of
distribution whereas girls from urban upper so~to-
abstract reasoning. Acceptance by the peer group becomes '
important. Sexual exp erimentation, such as masturbation, economic group show ma l nu trition . due. to eatmg
.
. d
d1sor ers. An .
orex1a nerv osa and bulimia are mcreasmgly
starts at this age.
reported.
La It! 11l111sc: By this time, most of the pubertal changes are Me11tal ltealth problems: Adjustment and .anxiety
already achieved. Moral values and strong self identity disorders, depression, suicide, delinquent b~hav1or, poor
are now established. They are now able to suppress body image and low self-estee~ are. maJOr concerns.
impulsivity and are less affected by peer pressure. Suicide rates are increasing, with higher number of
Personal relations become more important than the peer completed suicide in boys and attempt~d sui~i~es in girls.
group. The youth becomes career-oriented and starts Adolescents are at high risk of committing suicide beca~se
short- and long-term planning for his or her goals in life. of cognitive immaturity and impulsivity. Psychological
Many start engaging in sexual activity. disorders like depression or mood disorders, substance
abuse, parent-child conflict, physical or sexual abuse and
Attitude Towards He alth family history of suicide make them prone for such
Adolescents are considered to be at the peak of their health; attempts.
yet, adolescence coincides with the onset o.f ~any h:alth Sleep disturbances: During the period of rapid growth,
disorders. Girls are often unprepared for their first periods. adolescents have increased sleep requirements. Under the
High-risk behavior is common in mid-adolescent age
effect of physiologic delay in melatonin secretion,
group. The National Family Health Su~vey 4 (NFH~4) adolescents have a delay in sleep onset and awakening
reported the median age of sexual debut m boys.an~ .girls by almost an hour. In urban adolescents, this may be
to be 24 years and 19 years, respectively, but a s1gn1f1cant
compounded by increasing academic activity or watching
proportion are sexually active much before. Knowledge television late into the night. Poor sleep habits are likely
about contraception is improving among adolesce~ts. to reflect in school performance and cause daytime
Though awareness about HIV is increasing among Indian drowsiness, aggressive behavior, conduct disorders,
youth, most of them lack comprehensive knowledge of anxiety, restless leg syndrome and depression.
the disease.
Infectious: With increased outdoor activity, teens are
PROBLEMS FACED BY ADOLESCENTS exposed to TB, HIV, skin and parasitic infections and
sexually transmitted diseases. Early sexual activity is not
Adolescents are under immense pressure because of the uncommon. Various biological (immature, incompletely
rapid changes in their hormonal milieu, changing. ideas estrogenized mucosa) and psychosocial factors (lack of
and concepts about the world, having to cope up with ~he preparedness, knowledge r.egarding barrier contraceptives)
expectations from the society and the need to establish make adolescents susceptible to these infections.
their own identity. The problems faced by an adolescent
in India are diverse and are often not addressed by the Problems Specific to Females
health care system. It is common to have anovulatory_ and irregular menstrual
cycles during first two years after menarche. The
Health Problems of
polycystic ovary syndrom~' _a combination menstrual
Nutrition mid eating disorders: There is increase in irregularities and ovari31'1: cysts with androgen excess like
nutritional requirements during this period of rapid acne or hirsutis~, occu:s in -9% adolescent girls. Th~
growth, micronutrients being as important as energy and condition is assoc1~ted ~1th other metabolic derangements
protein (see Chapter 8). Data from the NFHS4 shows that like obesity; ins~ resistance and type·2 diabetes. ,·-.·. '.1
...
. . . ~~- ~· .
Adolescent Health and Development ea I
Mc11stn1al. hy~iene: There are many social taboos about overweight have been reported and sim~lar figures are
menstruati~n m Indian families. Many adolescent girls are available from other parts of urban India as well. The
found to nuss school during their menstruation because prevalence of obesity and overweight is higher in boys
oflack of access to safe sanitary products or lack of privacy. than girls. Obesity has strong associatio~ with as~hma,
~oor ~enstru~l hygiene may contribute to reproductive sleep disorders, reflux disease, Blou~t disease, shppe_d
in~echons . v;71th the introduction of government and femoral epiphysis, gallstones, fatty hver and . ~etabo.hc
private run Menstrual Hygiene Schemes', 57% young derangements like type 2 diabetes~ dyshp1dem~a,
women now use hygienic methods during menses. hypertension and polycystic ovary disease. Essential
[NHFS4] hypertension is rising, with preva~ence of 6'%i~ urban and
3.4% in rural youth in some studies from India.
Ge1z~ tal i~fections and sexually transmitted infections:
ya~al dischar?e is common in adolescent girls and may
indicate physiological leukorrhea of puberty, and
endogenous or sexually transmitted infections. Gonorrhea
can cause vulvovaginitis, urethritis or proctitis; Chlamydia
may cause intermenstrual or post-coital bleeds. Both may
Substance abuse: Most tobacco and alcohol use starts
during adolescence, in urban as well as rural India. The
Global Youth Tobacco Survey 2009 showed that 14°/r1 of
school youth reported using tobacco currently. Apart from
tobacco, alcohol (21 %), cannabis (3%) and opium (0.4%)
I I
be asymptomatic in majority and can cause vaginal are most abused substances. Addicts are prone to
discharge . Candidal infections become common with accidents, injuries, violence, trading sex-for-drugs, HIV,
starting of menstruation and often have a cyclic nature. hepatitis C, sexually transmitted diseases and tuberculosis.
Pelvic inflammatory disease (PID) is a spectrum of
inflammatory disorder of female genital tract, which Vulnerability
occurs in sexually active females and can present with
Abuse and violence (plzysical and sexual): Physical and
abdominal pain with vaginal discharge. Lower abdominal,
sexual violence is common in India, with 20-30% young
cervical or adnexal tenderness is suggestive of the
diagnosis (Table 5.1). females suffering from domestic violence and 5-9% young
females reporting sexual violence (NFHS4). Accidents are
Lifesttjle diseases: Obesity is the other end of the spectrum the major cause of mortality in this age group. Road traffic
of malnutrition and is epidemic in the urban settings. accidents, burns and poisoning are leading causes of
Among Delhi school children, 5% obesity and 17-19% traumatic mortality and disability in Indian youth. Motor
Candidiasis Itching, redness, white discharge Clotrimazole cream or pessary for 7 days, miconazole pessary . ,.
for 3 days or oral fluconazole 150 mg single dose
Pelvic inflammatory Polymicrobial; varied disease Mild to moderate illness. Oral cefixime 400 mg twice daily
disease spectrum for 7 days, metronidazole 400 mg orally twice daily for 14 days "'
and doxycycline 100 mg twice daily for 14 days; abstinence; . . ;
symptomatic treatment ·~jt}: r :
' -.
- 64
---------------------------E=s~s~e~n~tl~a~l~P!e~dl~a~tr~lc~s~----------~~~~--~---------.
vehicle and industrial accidents are common in boys · · t'ion is improving over the
-v
Illiteracy: Though the s1tua
whereas burns are more common in girls. ·11 3301 f I d' n youth are not able
years, s t1 10 o n 1a df to complete
mili fr
their primary education. Female gender an a es om
Mig ra i"ia11: Many adolescents migrate from rural to urban
rural and poor background are the risk factors for
settings, for labor or educational opportunities. Trafficking
of youth is a serious problem in India and happens for illiteracy.
industrial or domestic labor, forced marriages and Academic and emotional stress: Examinations cause
prostitution. In stales like Bihar, 70% of new HIV infections significant physiological and psyc~ological stress. Ap.art
are related to outward male migration. from change in body structure, vanous other .factors like
peer acceptance, discrimination, ac~dem1~ burden,
A rl oiesce11l 1'regnancy: Unmarried adolescents are likely
parental expectations and changing soC1al environments
to resort to unsafe methods of abortions, which increase
cause stress among youth. Switching from vemacu!~r to
risk of septicemia and mortality. As compared to adult
English medium schools, long hours of school and tuitio~
pregnancy, they are also at a higher risk for pre-eclampsia,
are additional stress factors that are on-addressed. While
-~~.;'!"! preterrn labor and postpartum hemorrhage. Prolonged
most adolescents have adequate coping skills, some have
and obstructed labor are common in adolescent
serious adjustment problems resulting in psychological
-~~~ pregnancies and they are 2-4 times more likely to die
during childbirth as compared to adult females. Neonatal, and somatic effects.
infant and child mortality rates are higher in children Early marriage: Though the legal age for marriage in
delivered to adolescent mothers. Fortunately, the India is 18 years for girls (Table 5.2), many states still
prevalence of adolescent pregnancy [8%] is lower in the have the practice of childhood and early marriage.
results of NFHS 4, due to schooling and knowledge about Almost 30% of Indian girls between the ages of 15 and
contraception. 19 years are married; the proportions are higher in rural
areas.
Lack of sex education: The majority of Indian youth do
not get formal sex education in an effective way. Peers, Discrimination: Young people are often treated as second
books and magazines are their main sources of information class citizens, under the control of adults and often not
about sex. Parents and teachers often fail to discuss issues involved in any decision making. Adolescent girls are
like masturbation, safe sex, dating, abortion, HIV and often asked to limit their outdoor I extracurricular
sexually transmitted diseases. activities, confined to their houses and expected to do the
household work. Gender-based discrimination is seen in
Environmental and Social Challenges education and even food distribution.
Pollution: The incidence of asthma is increasing. There Role of Health Care Provider
is ongoing research into the role of electromagnetic
exposure from communication devices in disorders like A checklist for the adolescent clinic visit is provided in
childhood leukemia, brain tumors and immune Table 5.3. During each visit, the following are important:
dysregulation. Identifying risks: The physician needs to detect risk factors
Media: With easy availability of electronic media, like ob.esity, hypert~nsion, possible substance/ drug abuse,
adolescents are exposed to unsupervised information from behavioral and social problems and risky behavior. Subtle
all across the world. Adolescents often succumb to cue~ like sad or depre.ssed mood, avoidance of eye contact,
glamorous portrayal of tobacco or alcohol consumption, brmses or undue resistance to examination are the likely
unrealistic expectations, physical aggression, destructive pointers towards physical or sexual abuse.
behavior and unprotected sex. Spending much of spare
time indoors on social networking sites, teenagers are
deprived of sunlight and physical activity and socially
! ~abt; ~:2: Legal ag~ definitiori_s ri:_le~a-~tI~~9J
Definition of child Below 18 years·-. :,__,; ·. ·\
isolated.
Minimum age for marriage Boys 21 years; girls 1-8 ~ea~!
Peer pressure: Peer formation is a part of adolescent social Responsibility for crime 12 years . '; ~ . "..~ ~
- ·~ 'f,· -·:·~•.r:r-: ~. •' . . ' t- ": ..
development. Pressure for conforming to norms drives Juvenile criminal 12-18 years .-:·:. ·" ~: ;;
many of their actions and decisions, including risk taking Compulsory free education 6-14 years -. ·:· •· .· ... . ,. . /'1
behavior and initiation of substance abuse.
Consumption of alcoh.ol . Beyond 1~2dy~a~·in ... ;~. ;
Poverty: Adolescents belonging to poorer families are , • ,- , _,di~_erent states (illegal in:;:'"":;
likely to have inadequate diets. Studies have shown that '. . , .: .:, · ; , . · some states and union -~ }(/~ .
children belonging to poorer families had higher chances 1· >.-.· "' •• 1 -~ .:. ~ ~erritoriesj . -· .· ,-'·'.;:
of having depression, anti-social behavior and engaging • ·
Employm~nt'in
•·
hai'.arifous:
~> 14 years . . . . . ~.-~/' ~.-::-:,:. :\":;
h. tels : .. L .,.· ' · , .. ·.- · · · -" ::":" ~·:!.,.:,_ ···; t
in drugs or sexual activity at earlier ages. L-0-~~p~~f!Efr~~J.'.:·~.:.i:·L.t'_
. . . ...i.:: -~·,;.3.,::_., J;_~'~"""''
-··-6-.f.•.·~,·-~<
,.__.. -:'1
~
',.. ·? ' : .• _ .•
Adolescent Health and Development 65 -
-.- -......... ·-~~-.,.-
- -... -)ro .......
Physical examination
Relationship with family
Level of communication on sensitive matters
Anthropometry
Blood pressure, markers of obesity, acanthosis
I
Sexual maturity rating
Signs of malnutrition, anemia and vitamin deficiencies
Signs of skin and genital infections
Level of general hygiene
Signs of trauma; abuse
Signs of drug abuse or tobacco use
Counseling Nutritional intervention
Hygienic practices
Building rapport between parents and adolescent
Providing information and sources on sex education
Investigations Hemoglobin level
Blood sugar, lipid profile
Genital swabs
Ultrasound of ovaries
Referrals Counselor
Dietitian
Psychiatrist
Gynecologist
Voluntary and confidential HIV testing
Social services, child protection agencies, support groups
Establisliing rapport: Being empathetic and non- Consent: For a child who is less than 12 years, consent for
judgmental is the key to effective communication. Direct examination or medical/surgical procedure is obtained
questioning of the adolesce~t is as.impo~ta~t as questioning from the parent or guardinn. While an adolescent aged
the parents. Beginning the. mterv1e~ with icebreakers, ~se 12-18 yenrs can give consent for examination, consent for
of open-ended non-sensiti~e q~estions and then movmg medical/ surgical procedure can be g iven only after
to sensitive/targeted questions 1s helpful. 18 yen rs. This also includes consent for medical termination
of pregnancy, blood and organ donation.
Confidentiality: One may need to interview a young
patient separately, as he/she may not want to disct~ss N11tritiu1111/ i11tcn1t•11tic111: Improving the nutritional status
sensitive topics in the presence of pnrents. While of ndolescent girls helps in two ways. It breaks the cycle
examining the genitalia, the doctor can ask patient's of malnutrition and low birth weight babies, and prevents
preference for presence of their parent ins ide the long-term complications of the latter in future generations.-
examination room. A boy may prefer his parents standing
outside the exam room, whereas a girl may find it Providi11g l1c11ltlt i11formatio11: The adolescent health visit
comforting, if her mother accompanies her during the is an excellent opportunity to talk to the parents and their
examination. adolescent about the pubertal changes. It is likely thauhey
66
have not received any formal sex education in school and rm::::11lmU~t.iiM@fJ§.m.Mi
• :rztJliWfl"!\'1• 1·00~~
need to be provided correct educational resources for the ~ flealtl1y lifesh;fc '
same.
• Healthy food
Refemi! to social service:>, psycl1ologicnl cva /11ntion attd '• Exercise and Yoga
s11p/)orl: National Commission for Protection of Child • No to tobacco, alcohol, drugs
Rights Act 2005 considers a person below 18 years as a • Safe conduct on road
'child'. It is mandatory for a health care provider to report Vaccines
all cases of child abuse (even suspected) to the Chairperson • Papilloma virus, rubella
of the Commission; the complaint can be lodged online Anemia . .
or in w riting. Doctors are protected in case of erroneous · detection
• Prevention, · and management of anemia / especially
reporting but punishable, if they fail to report. Adolescents for adolescent girls
with special needs or victims of any kind of abuse need
Sexual health
social and psychological support.
• Sexuality education
Adofcsce11t-fricndly healtlr services: Adolescents have • Menstrual hygiene
diverse problems and special needs. The services include • Marriage after 18 years, childbirth after 20 ~ears
provision of reproductive health services, nutritional • Counseling and services for comprehe~s1ve sexual and
counseling, sex education and life skill education. reproductive health, including contraception
Confidentiality, easy accessibility, friendly attitude and Mental health
quick comprehensive health care delivery have made a • Supportive family; counseling and peer/family support in
pos itive impact on adolescent clients. 'Adolescent anxiety, depression
reproductive and sexual health' has been identified as a • Prevention and management of hazardous and harmful
key strategy under RCH II programme. Adolescent substance use
friendly clinics are functional at many centers in the , • Prevention of suicide and management of self-harm/suicide
country. Box 5.1 lists the key services and interventions risk
that should be provided for comprehensive care for Violence prevention
adolescents. • Prevention and management of unintentional injury
• Prevention of and response to sexual and other forms of
Management of sexual violettce: This includes the gender-based violence ·
following measures:
i. Forensic examination and collection of blood or body · Co11111111nicable and non-comm11nicable diseases
fluid samples by trained staff. • Prevention, detection and treatment of communicable and
non-communicable diseases
ii. Care of the injuries. 1
I ·.: f
~· • I.
- '. .'-. ,,_ .."' I
- Adolescent Health and Development
167 -
. '· ·.-.-~---~~~.T~ble 5.4: lmmunlz;\k;~ci~;l~g-;-dole;cence ~~--.-~·-or.-- ~.- -~r:...:-z.i)
T~tanus and dlPhth'E;ria-t~~oid·~ ·and ac~llui~r pertu.ssi~ - - - 10-12 years, and 'every 10 years th~reafter -~·
(Tdap) vaccine ITT at 10 and 15 years as per Universal i
Immunization Program]
• Papillomavirus
2 doses, If given between 9 and 14 years
3 doses, If given beyond age 15 years
Influenza
Annually
Catch-up vaccination is discussed in Chapt~r 1o
Transition to adult care: With better medical care, a large health, National Health Mission now follows
I
~umber of chronically ill or disabled children are surviving Reproductive, Maternal, Neonatal, Child and Adolescent
into adulthood. As the problems of these children are Health (RMNC+A) approach. Under this program, weekly
diverse, they need multidisciplinary care even in their iron and folic acid supplementation (WIFS) program
adulthood. Transition to adult care is not mere transfer of provides 100 mg of iron and 500 µg folk acid with biennial
the case to a different physician. It is a gradual and planned deworming to all adolescents attending government
process; keeping in mind the abilities of the child to schools.
participate in self-care, taking responsibilities and decision
making. The age at transfer is not fixed; a window of age Suggested Reading
14-18 years is used in some countries for a gradual 1. National Family Health Survey [NFHS3, 2005-6] and [NFH.54, 2015-
transfer. 16). International Institute for Family Survey, Mumbai.
2. WHO Media Centre Fact Sheet 2014. Adolescents: health risks and
GOVERNMENT INTERVENTIONS IN solutions.
3. Contraception and Adolescents: Committee on Adolescents,
ADOLESCENT HEALTHCARE Pediatrics 2007;120:1135.
Kishori Shakti Yojana and SABLA Yojana aim to provide 4. National Guidelines on Prevention, Management and Control ofRTis/
STis. Ministry of Health and Family Welfare, Govt of India, 20CJ7.
health, nutrition, education and vocational skills to 5. Dietary Guidelines for Indians [Second Edition]. National Institute
adolescent girls. National Youth Policy believes in youth of Nutrition, 2011.
empowerment through education. Recognizing the 6. Juvenile Justice Act 2015. The Gazette of India, Ministry of Law
contribution of adolescent care to maternal and child and Justice.
. ·l :~
....
_
.-: . ' :-
Chapter
6 Fluid and
Electrolyte Disturbances Kamran Afzal
Fig.
I\
6.2: Balance of water Intake a nd 1osses maintains normal plasma osmolallly. Only water lntako and urinary losses can be
regulated
~-··············-----------~
140 ' '
140 Plasma lntrncollulnr
120
104
100
_, 80
::.
0
E 60
E
40
20
the brain having the least and the liver the most per- nnd the secretion of nntidiurl'lic hormone (ADH) (Fig. 6.4).
meability. However, water readily crosses cell membranes Plnsmn osmolnlity cnn be mcnsured directly using
to achieve an osmotic equilibrium between the two osmometers, ns wc11 ns eslimntcd lndil'cctly ns follows:
compartments. The balance and appropric1te distribution ' l glucose blood men nltmgcn
Plnsmn osmoInIlly"' 2lN n +
of fluid within these spaces is maintained by the colloid 18 + l.S -
oncotic pressure, membrane p~rme~bility a.nd ~1ydrost~tic Mensmed vnlucs nrc gcncrnlly higher thnn cnlculntcd
pressure. Plasma and interstitial flmd are nch m protems, vnlues by up to 10 mOsm/kg nnd this difference is cnlled
which determine plasma colloid oncotic pressure.
osmolnl gnp. lncrcnsc In osmolnl gnp mny occu1· due to
incrensc in unmcnsmcd osmolcs.
Osmolallty
Osmolality (expressed as milliosmoles pe.r kilogram .of Normal Maintenance Fluld and
water, mOsm/kg) is the solute concentration of a flm~. Electrolyte Requirements
Changes in osmolality can produce grave neurologtc
consequences and even death, primarily due to water !he m~nrml mnintcmmcc wntcr requh·cmcnt is eqtml to the
movement into and out of the brain. To prevent this, the ms.ens~blc nnd urinnry wntcr losses. Hollidny nnd Scgm·
plasma osmolality, which is primarily determ.i ned by the gutdclu1cs (1957) cnkulntc mnlntennncc fluid volum~s to
plasma Na+concentration, is normally maintamed closely mntch electrolyte-free wnter requirements from esthnntes
between 1 and 2% of the normal (285 to 295 mOsm/kg) by of water of evnpomtion (hcnt dissiplltlon) nnd cnloric
appropriate variations in ~ater intake and ~ater excretion. exp~ndlturc (hent productloi\). They cstlmnted n dnlly
This regulatory system ts governed by different osmo· sodmm requirement of 3 mEq/kg, pohlssium nnd chlmld~
receptors in the hypothalamus that influence both thirst 2 mEq/kg ench nnd dnily glucose rcqulrement l\S 5 g/kg
70
Fluld loss
Anglotensin I
Renin
J_ Angiotensinogen
~ Anglotensln·converting enzyme
fl/i~
Free water teabsorptlon Angiotensin II
In distal tubules and +. Adrenal
collecting ducts Aldosterone release ~
based on the electrolyte composition of human and cow 5% dextrose in water or 0.2% or 0.45% saline (without
milk nnd rcconu11cnded 30 mEq/L sodium chloride (saline) dextrose) should be avoided. There is considerable
for maintenance fluid in children. Maintenance IV fluids in evidence that use of hypotonic fluids in sick hospitalized
nn unwell child may be initiated with 0.45% normal saline patients increases the risk of hyponatremia several fold.
along with 5% dextrose and 20 mEq/L of potassium Normal saline (0.9%) can be safely administered in
chloride (provided urine output is adequate) . This standard maintenance volume without risks of
composition may be modified according to the clinical state. hypematremia or fluid overload, except in patients who
The guidelines for maintenance volume (Table 6.1) assume are fluid restricted (e.g. congestive heart failure, liver and
average calorie expenditure in a healthy child. Fluid renal ~ailure) ~n~ ~hose with renal concentrating defect
requirements change considerably in different clinical (e.g. diabetes. ms1p1dus)'. ~ypotonic fluid should only be
conditions (Table 6.2). used to achieve a positive free-water balance as in
IV fluid with osmolality lower than plasma osmolality replacing renal or non-renal loss of electrolyte-free water.
can cause movement of free water from plasma to red The ideal volume for maintenance fluid is debated.
blood cells leading to hemolysis. Therefore, infusing plain Conventional calculation using weight-based formulae
often lead to overestimation o~ electrolyte-free water, and
Table 6.2: _Condltlo~~ th~talter"~alnten~~e _fluid needs I excess free water retention that predispose to
• Increased fluid requirement Decreased fluid requirement hyponatremia. Therefore, it may be prudent to restrict
j
Fever (10-15% per 0 c Oligurla or anuria maintenance fluids to 40-60%, especially in critically sick
above 36°C) Humidified ventilator or children. Fluids should be limited around 400 mL/ m2 in
Radiant warmer, incubator renal failure with oliguria. There is no single maintenance
phototherapy Hypothyroidism intravenous fluid which is suitable for all clinical scenarios
· Bums, sweating and maintenance fluid prescriptions should be
Physical activity; individualized. All children receiving IV maintenance
hyperventilation
fluid should be monitored with daily weight fluid
Dlarrh~a, vomiting .' balance, clinical and biochemical parameters in 0 ;der to
folyuria, renal .
maintain homeostasis. Additionally, maintenance IV
. concentrating defects
fluids do not replace daily nutrient requirements and
·' Very low birth weight babies
provide only 20% of daily calories (enough to avoid
(large su"rface a_rea) . 1 •
I • ....-. !.- • , • ,...·. • •·~- ' - - -
~ ..i: ••, J.,. •
' .1 ' starvation ketoacidosis and diminish protein degradation).
Fluid and Electrolyte Disturbances 71 •
I
Urine output Slightly decreased Decreased Oliguria, anuria
DEFICIT THERAPY lactate, that mimic plasma composition better than normal
saline may be considered, especially in the setting of '
The ~egr~e of volume depletion is assessed by physical
acidosis.
examination (Table 6.3). The process of hypernatremia or
hypertonicity decreases the severity of physical signs of
SODIUM
volume depletion. All fluid lost should be replaced daily
to maintain euvolemic state. Steps for providing fluids Physiology
and electrolytes to volume depleted patients are: Sodium is the most abundant ion of the extracellular fluid
• If the patient shows signs of shock, compensated shock compartment and is critical in determining extracellular
or features of severe dehydration (Table 6.3), rapidly and intracellular osmolality. Normal serum sodium
infuse isotonic fluids to restore intravascular volume. concentration varies between 135 and 145 mEq/L.
This is done by infusing 1 to 3 fluid boluses of isotonic Extracellular sodium balance is determined by sodium
saline or Ringer's lactate, 20 mL/kg body weight. . intake relative to sodium excretion. Daily sodium
• Provide fluids to replace calculated/observed volume requirement is 2 to 3 mEq/kg body weight although
deficit. This is calculated as volume at the rate of 10 mL intakes are generally well in excess. The requirement
for each percentage weight loss. For example, in varies with age. It is nearly two- to threefolds higher in
patients with moderate (some) dehydration, which is term and very low birth weight preterm babies, a reflection
on an average 7.5% weight loss, the replacement of immaturity of renal tubular function and higher
volume is 75 mL/kg body weight. If the pre-dehy- requirements for growth. Adult requirements decrease to
dration weight is known, the volume of fluid needed 1.5 mEq/kg/ d . Urinary sodium excretion represents the
is 1 liter for every kg of weight loss. majority of sodium losses and approximately equals the
• Provide fluid and electrolytes to replace the amounts daily intake of sodium. Fractional excretion of sodium is
lost in normal daily m etabolism (maintenance fluids) . generally less than 1% of filtered load. Extrarenal sodium
losses can be significant v ia profuse sweating, bums,
• Provide enough fluid to replace ongoing losses of
severe vomiting or diarrhea.
various body fluids (Table 6.4).
A fall in blood pressure, decrease in sodium delivery
While current literature does not advocate use of one
to the macula densa, or sympathetic stimulation may
type of fluid over another, there is a growing concern of
activate the renin- angiotensin axis, generating angiotensin
hyperchlorernic metabolic acidosis ~ith fluid resus:itation 1 II. This results in increase in blood pressure and sodium
wi_th normal saline. Balanced flmds, such as Ringer s
retention caused by enhanced aldosterone secretion. The
.·Table.s:4~1ectro~7onipo~it!or~ b9dY flu.ids .l effective circulating volume refers to that part of the
extracellular fluid that is in the arterial system and is
Lo~~es': · ~... tia~ , . .. · I(+ · · ·.: er: ,· Hco3- ! effectively perfusing the tissues. The effective circulating
(m£q!LJ , 1 ·· (rn£q!LJ . (m£q!L) . (f!1£q/LJ 1
, volume usually varies directly with the extracellular fluid
Gastric 60-100 5-20 90-130 0 volume, and both are proportional to total body Na+
·Small intestine 80-140 · 5-15 90-140 - 40 stores .. As .a :esult: the regulation of Na+ balance (by
Colon · 60 30 40 .. 15 alteration in its urinary excretion) and maintenance of
effec.t ive circulating volume are closely related. Sodi~
Pancreas . " 135-145 . '5-10 - . 70-90 95-, 20 .
Diarrhea ·
... ~~-- . -·"
10-90 ·· ..:· .1~o 90-130 "· 4.0_'. ~ ..._,J loading tends to produce volume expansion, whereas loss
leads to volume depletion. · · · - ' ··
7~ ~~~~~~~~~~~~~~E~s~s~e~n~t~ia~l~P~e~d~ia~t!rl~c~s~~~~~~~~--~~~~~~~~~~-/
.. an d confusion . Ad va nced
U)lponotromla nausea, vom1tmg, lethargy . d ticate p o<Jturing,
. . coma eco r
I l\·110n,\ln' mi:l, d.d ined as plasma :-odium less than manifestations are seizures, ' d ' c arrhythmias
ils . . iUedema, car i.a '
t 35 mEq / l.. ,·,rn r\'.'sult from t>:xccssiw loss of sodium from dilatedpup , arusocona, pap
1
d ' abe tes insipidus.
myocardial ischemia and centra ~ mEq / L or Jess.
eX\'.''::siY,~ ::wealing, \'omiti ng, d iarrhea, burns and the
;hhninistr.\liut\ of diuretics (fable 6.5). The most common Cerebral edema occurs at levels of 1 2 . t th ,
. flux of w a ter tn o e
C-1\l::e tit' hypon.ltremia, however, is not a deficiency of Hypo-osmolality causes in . t toxic cerebral
tnl.ll body sodium, but an excess of total body water, as intracellular space, which results m c~r~ and can lead
in the syndrome of inappropriate antidiuresis (SIAD). edema and increased inn:ac:anial ~re;!ath. The brain's
Sli\D is seen in association with pulmonary and cranial to brain ischemia, herniatio_n an h natremia is the
disorders '1nd posloperati\·ely. High levels of vasopressin primary mech~sm in adapting t~ot~~s and organic
or nntidiuretic hormone (ADH) are secreted at a low extrusion of intracellular e~ect ~ tes are excitatory
thr\'.'shold or continuously despite low osmolality. The osmolytes. Some of these organic osmdo y tate that can
presence of hyponatremia' plus a urine osmolality higher . 'd h s glutamate an aspar
ammo ac1 s, sue a f d tectable cerebral
th;m nrnximal dilution confirms the diagnosis. SIAD produce seizures in the absence 0 e tr .
should be differentiated from cerebral salt wasting which edema Major risk factors for developing hdyponal e~icl
· hyp~~am n~ro~~
i~ also associated. with central nervous system disorders. encephalopathy are young age, · · k than are
In the l:ltter, there is hypovolemic hyponatremia and high disease. Children are at significantly higher ns
urinMy sodium (>80 mEq/L} due to increase in blood adults for developing hyponatremic ence~halopathy d~e
lcn~ls of natriuretic factor(s). SIAD is characterized by to their relatively larger brain to intracran1al v~lu~e ra~iho
eu\'olcmia or mild volume expansion, inappropriate compared w1'th a dults · Hyponatremia in association lm wit
urinary concentration (urine osmolality > 100 mOsm/kg), increased intravascular volume can result in pu onaiy
nnd high urine sodium (>20-30 mEq/L}. In presence of edema, hypertension and heart failure. ~symp~omatic
elcv<lted ADH levels, there is impaired ability to excrete hyponatremia in preterrn neonates is assoaate.d with poor
free wnter with the urine osmolality exceeding that of growth md development, sensorineural heanng loss and
plasma. The treatments are different, as cerebral salt a risk factor for mortality in neonates who suffered
wasting requires replacement of urinary salt-water losses perinatal birth asphyxia.
while SIAD is managed by fluid restriction.
Hyperosmola\ity resulting from non-sodium molecules Treatment
(hyperglycemia, maimitol overdose) draws water fro~ the The first step is to determine whether hyponatremia is acute
intracellular spnce to dilute the extracellular sodmm ( <48 hours) or chronic (>48 hours), symptomatic or
concentration. Fnctitious hyponatremia, reported when asymptomatic and evaluate the volume status. In
hyperlipidemia (chylomicronemi~) or hyp:rproteinemia hypovolemic hyponatremia with hypotension, volume
coexist, is uncommon due to use of ion-selective electrodes.
resuscitation with normal saline takes precedence over
Patients are generally symptomatic when ser~m treatment of hyponatremia even at the risk of sudden
sodium concentration falls below 125 mEq/L or the decline increase in serum sodium. Symptomatic hyponatremia
is acute (<24 hours). Early features include headache, requires early recognition and prompt mangement with
IV boluses of hypertonic saline irrespective of the chronicity
Table s:s: Causes of hyponatremla - .
of hyponatremia. Oose biochemical ar\d clinical monitoring
. Hypo~olemlc hyponstremls (sodium loss_ In excess of free should be provided during mar\agernent (Box 6.1).
water) _
In asymptomatic cases, the underlying etiology needs
Rensl toss: Diuretic use, osmotic diuresis, renal salt-wasting,
to be evaluated and corrected. Losses due to renal or
adrenal Insufficiency, pseudohypoaldosteronism
adrenocortical diseases are suggested by urinary sodium
Extrarenal loss: Diarrhea, vomiting, drains, fistula, sweat (cystic concentration of more thar\ 20 mEq/ L in the presence of
fibrosis), cerebral salt wasting syndrome, third-spacing
clinically relevant volume depletion (Fig. 6.5). Chronic
(effusions, ascites)
hyponatremia should be slowly corrected over 4~72 hours.
. Normovolemlc hyponstrelT!la (conditions that predispose, Aggressive therapy with hypertonic saline in patients with
\ to SIAD) ; chronic hyponatremia (where brain adaptation to hypo-
~ Inflammatory central nervous system disease (meningitis, osmolality is set in by extrusion of intracellular electrolytes
oncophalllls), tumors ar\d organic osn:'oles) can lead to osmotic demyelination
Pulmonary diseases (severe asthma, pneumonia)
syndrome. Patients .who .develop the demyelination
Drugs (cyclophosphamide, vlncristine)
Nausea, postoperative
syndrome show a b1phas1c course, with neurological
improvement follo~ed by deterioration 2-7 days later
HypeP/otemlc hyponstremls (exces~ free water retention)
1 manifested by mutism, dysarthria, lethargy, spastic
Congestive heart failure, cirrhosis, nephrotic syndrome, acute : quadriparesis and pseudobulbar palsy. In clinical practice,
or chronic kidney disease · ' the distinction between acute ar\d chronic hyponatremia
.. - .......... .
113 -
Hyp-ovore~la ]
-·----. - - - - -- --·
Euvolemla Hypervolemla
lal body water J. I Total body water t Total body water tt
Total body sodium t
body sodium !J. Total body sodium H
· --.-- - J
___y __ ~ !
______
IR~nal. losses
.._
1U (Na•] >20
-
I
- I
Iu (Na•]~~
Extrarenar-
~·
SIAD Acute~c Nephrotlc syndrome
Di.uretics ~ losses Glucocorticoid deficiency renal failure Cirrhosis
ISalt losing nephropathy
I
Mineral~cortlcoid deficiency Vomiting
Diarrhea
Hypothyroidism
Stress
Congestive heart failure
Fig. 6.5: Diagnostic approach to hyponatremla. U[Na•J urinary sodium, mEq/L; i Increased; .!. decreased
I
into cells. The reverse happens with glucagon, a-adrener-
Box 6.2: Treatment of hypernatremla- gic stimuli and acidosis.
• Restore in~ravascular volume with 20 mL/kg normal saline , Hypokalemia
over 20 nun (repeat until intravascular volume restored) Hypokalemia is defined as a serum potassium level below
' • Determine time for correction on basis of initial sodium ! 3.5 mEq/L. The primary pathogenetic mechanisms result-
concentration: ing in hypokalemia include increased losses, decreased
Serum sodium level Time intake or transcellular shift (Table 6.7). Vomiting, a
145-157 mEq/L 24 hours common cause of hypokalemia, produces volume deple-
158-170 mEq/L 48 hours tion and metabolic alkalosis. Volume depletion leads to
171-183 mEq/L 72 hours secondary hyperaldosteronism, which enhances sodium
184-196 mEq/L 84 hours resorption and potassium secretion in the cortical
• Fluid for correction 05 N /3 to NI 4 normal saline (~ith , collecting tubules. Metabolic alkalosis also increases
1 20 mEq/L KCl unless contraindicated)
potassium ~ecretion due to the decreased availability of
• Fluid rate: 1.25-1.5 times maintenance t
1 hydrogen ions for secretion in response to sodium
• • Monitor serum sodium q 4 hourly; should not fall by >0.5 reabsorption.
mEq/L/hour
1 • Adjust fluid on basis of clinical status and serum sodh~m 1 . Regardless of the cause, hypokalemia produces similar
concentration; if child develops seizures (due to rapid ~ signs ai:d symptoms. Symptoms are nonspecific and
correction) 3% NaCl (4-6 mL/kg over 30 min) is indicated.! predominantly are related to muscular or cardiac function.
.• Replace ongoing losses as they occur i Severekn hypokalemia (<2 ·5 mEq/L) m ay cause muse1e
\ ·• Ide~~fy ~d _treat ~e _unde~lying cau~e ) wea ess (ne~k flop, abdominal distension, ileus) and
produce cardiac arrhythmias. Chronic h k . .
· t d ·h · ypo a1errua is
0.5 mEq/L/hr should be the goal rate of correction. Renal associa
th e wit
· interstitial renal d' f
isease o uncertain .
replacement therapy is indicated for concurrent renal pa ogenes1s. Hypokalemia increases th . k 0 f di 0 .
failure and volume overload. toxicity by promoting its binding tom et ns ? '.°°
its action and decreas·mg c1earance. Y0 cy es, potentiating
POTASSIUM Treatment
Physiology Patients should be evaluated to d e termine
. the underlving
Potassium being a predominantly intracellular cation, its causes an d d etermine whether it is . r-:·
blood level is unsatisfactory indicator of total body stores. hypertensionandacidosiso alkal . . associated with
Normal serum concentration of potassium ranges between may be a clue to primary ~yper~~JS (Ftig. ~.6). Hypertension
. th f os erorusm, renal arteiy
3.5 and 5 mEq/L. Common potassium-rich foods include stenos1s, or e rarer arms of geneticall . .
meats, beans, fruits and potatoes. Gastrointestinal tension such as congenital adre 1 h Y inhent~ hyper-
absorption is complete and potassium homeostasis is corticoid remediable hypertensi:a ~erplas1a, gluco-
Relative hypotension and alkal . n or iddle syndrome.
maint~ined predominantly through the regulation of renal osis suggests di ti
ex~reti~n. The fractional excretion of potassium is about
a tubular disorder such as Bartter . ure c use, or
· · or Gitelman syndrome
10 Yo, chiefly ~egulated by aldosterone at the collecting duct. Therapy mvolves decreasin . ·
Renal adaptive mechanisms maintain potassium homeo- discontinuation of diuretics, _g on~omg . losses (e.g.
.. <X:z agorusts), replenishing
~----~~------~------~~~~~~~~~~~~~~~~~
Fluid and Electrolyte Disturbances ! 1s -
Hypokalomla l
(sorurn K• <3.5 mEq/L)I
i --
Exclude spurious values I
l
(e.g. collular uptake In leukocytosls)
* -
Urine K• <20 mEq/L, TIKG <4- ~-{Spot urine potassium, s~ru~ ·; ,d [--.----.[ Urine K• >20 mEq/L, TTKG >4
(nonrenall c~use) - - urine osm~lallty, 11:~~-- .
~nal K• losses)
I l
Transcellular shift
Insulin, ~-adrenerglc agonlst,
alkalosls, periodic paralysis RTA type 1, 2 Primary hyperaldosteron-is_m_ _, Diuretics
Poor Intake Diabetic ketoacidosls congenital adrenal hyperplasia Bartter and Gitelman
,~- ··-.
An_:>~exla ~erv~s~ _ _
.. . .
_
of hypokalemia
I
-Increased losses • IV supplementation
Renal Indication: Symptomatic patients, severe hypokalemia ;
Renal tubular acidosis (proximal or distal) (<2.5 mEq/L), ECG abnormalities
Drugs (loop and thiazide diuretics, amphotericin B, - Potassium chloride (15%; 2 mEq/mL; 0.5-1 m.Eq/kg/
aminoglycosides, corticosteroids) dose) given as IV infusion over 1-2 hr. Infusion rate
Cystic fibrosis should not exceed 1 mEq/kg/hr; concentration of .
Gitelman syndrome, Bartter syndrome, Liddle syndrome potassium should not exceed 60 mEq/L (peripheral line) '
Ureterosigmoidostomy and 80 mEq/L (central line) -
Mineralocorticoid excess (Cushing syndrome, hyperal- • Oral supplementation
dosteronism, congenital adrenal hyperplasia (11 ~-hydroxylase, - Dose: 2-4 mEq/kg/ day in 3-4 divided doses
17ll-hydroxylase deficiency) - Potassium chloride (10%; 20 mEq/15 mL); potassium
High renin conditions (renin secreting tumors, renal artery citrate used in renal tubular acidosis. Liquid preparations l
stenosis) are bitter and may be diluted with juice or water
Extra renal • Stop and replace ongoing losses, volume resuscitation with 1
Diarrhea, vomiting, nasogastric suction, sweating normal saline, correct hypomagnesemia, treat underlying
Potassium binding resins (sodium polystyrene sulfonate) etiology ·)
Decreased Intake or stores renal insufficiency, acidosis and diseases that involve
Malnutrition, anorexia nervosa defects in mineralocorticoid, aldosterone and insulin
Potassium-poor parenteral nutrition
function. Sudden and rapid onset of hyperkalemia is one
Intracellular shift of the most serious electrolyte disturbances and result in
Alkalosis, high insulin state, medications (~ 2 -adrener~ic severe cardiac arrhythmia.
agonists, theophylline, barium, hydr~xychloroq~me), ref~edmg Factitious or pseudohyperkalemia can occur because
syndrome, hypokalemic per.1od1c pa~alys1s, malignant of the practice of squeezing of extremities during phle-
hyperthermia, thyrotoxic periodic paralysis ·· botomy or blood sampled from a limb being infused with
potassium-containing fluid or hemolysis of a standing
potassium stores (oral or intravenou~ ~dministration of sample. Thrombocytosis and leukocytosis can also lead
potassium chloride) and disease-specific therapy for the to false elevation of serum potassium levels. True hyper-
co d'ti has Bartter and Gitelman syndrome (e.g. kalemia is caused by one or more of three mechanisms:
n i ons sue inhi'b' )
indomethacin, angiotensin-converting enzyme itors Increased potassium intake, extracellular potassium shifts
(Box 6.3). and decreased excretion (Table 6.8). Increased potassium
I
intake may result from inappropriate intravenous or oral
I Hyperkalemla potassium supplementation. Packed red blood cells have
I Iiyperkalemia, defined as serum potassi~m le~el high concentrations of potassium that can lead to
lceeding S.5 mEq/L, is most commonly associated with hyperkalemia. Acidosis results in transcellular potassium
76 Essential Pediatrics
-
Table 6.8: Causes of hyperkalemla G' I , 1,• '. j :o • • :l'fl} • ~ ..~·<:
I " . ...-~ . m-containing fluids and
Decreased losses • Prompt discontinuation of potassiu .
Renal failure medications thnt lead to hyperkalemta t cardiac
. 11 1brane to p reven
Renal tubular disorders: Pseudohypoaldosteronlsm, urinary •Stabilize myocardi al c:~ me ~ •luconatc (or calcium'
tract obstruction arrhythmia. Use IV 10 Yo calcnu:i g . . under cardiac '
Drugs: ACE inhibitors, angiotensin receptor blockers, c,11on'd e)' a t 0.5-1 mL/ kg over 5-10 minutes
d . develops .'
potassium sparing diuretics, NSAIDs, heparin monitoring. Discontinue, if brady~ar ia ~
Mineralocorticoid deficiency: Addison disease, 21-hydroxylase • Enhance cellular uptake of potassium 1 . r I
deficiency, 3P-hydroxysteroid dehydrogenase deficiency Regular insulin and glucose IV: (0.3 U regu ar msu m g t
Increased Intake glucose over 2 hr) · ht
Sodium bicarbonate IV: 1-2 mEq/kg body weig over
Intravenous or oral potassium intake; packed red cells
transfusion 20-30 minutes buJ' d
~-adrenergic agonists (salbutamol, terbutaline) ne ize or
Extracellular shift IV ,I
Acidosis, low insulin state, medications (~-adrenergic blockers, • Total body potassium elimination
digitalis, succinylcholine, fluoride), hyperkalemic periodic Sodium polystyrene sulfonate (Kayexalate) oral/per.
paralysis, malignant hyperthermia rectal: 1 g/kg (max. 15 g/ dose) oral or rectal enema m
Cellular breakdown 20-30% sorbitol
Loop or thiazide diuretics (if renal functi~n is maintaine.d)
Tumor lysis syndrome, rhabdomyolysis, crush injury, massive
hemolysis • Hemodialysis: For severe symptomatic hyperk~lem1a,
particularly in patients with impaired renal functions or
shift, but any cellular injury that disrupts the cell mem- tumor lysis
brane (e.g. tumor lysis syndrome, rhabdomyolysis, crush • Primary or secondary hypoaldosteronism: Require
maintenance steroids and mineralocorticoid supplements '
injury, massive hemolysis) can cause hyperkalemia.
Patients may report nausea, vomiting and paresthesias
or nonspecific findings of muscle weakness (skeletal, taring should be performed. Treatment should be
respiratory), fatigue and ileus. Clinical manifestations are individualized based upon the presentation, potassium
related to the effects of elevated potassium levels on cardiac level, and ECG changes. If the hyperkalemia is severe
conduction since they interfere with repolarization of the (potassium >7.0 mEq/L) or the patient is symptomatic
cellular membrane. ECG changes appear progressively with ECG changes, therapy should be initiated promptly
with rising serum potassium and include tall, peaked with intravenous calcium gluconate, followed by sodium
T waves (5.5 to 6.5 mEq/L), prolonged PR interval, flat P bicarbonate, insulin-glucose infusion and/ or nebulized
waves, wide QRS complex (6.5 to 8.0 mEq/L), absent P 132-agonists. Hemodialysis may be needed in the more
waves, bundle branch blocks and eventually sine waves refractory patients. Milder elevations (5.5-6.5 mEq/L) are
(>8.0 mEq/L). managed with elimination of potassium intake, dis-
The transtubular potassium gradient (TTKG) accounts continuation of potassium sparing dmgs and treatment
for the confounding effect of urine concentration on of the underlying etiology. Children with primary or
interpretation of urine potassium excretion. secondary hypoaldosteronism require stress-dose steroid
supplements and mineralocorticoids.
(urine potassium x serum osmolality)
TIKG=
(serum potassium x urine osmolality) CALCIUM
This test cannot be applied when the urine osmolality
Physiology
is less than the serum osmolality. Normal TTKG varies
between 6 and 12. It should rise to >10 in patients with Ninety-eight percent of body calcium is found in the
hyperkalemia. A value <5 signifies in appropriate skeleton ~hich is iX: equilibrium with the extracellular
aldosterone effect. An increase in TTKG >7 after con~entra~on ~f calcium. Approximately 1to2% of body
administration of physiologic dose of fludocortisone calcmm exists I~ the ECF for physiological functions like
suggests mineralocorticoid deficiency; <7 suggests blood coagulation,
. cellular communication, exocyt os1s, ·
resistance. endocytos1s, muscle contraction and neur l
. . C . ff omuscu ar
transmh1~s1oni . a 1c1~~,d~ ects the intracellular processes,
Treatment throug its ca c1wn- m mg regulatory protein, calmodulin.
Hyperkalemia is a medical emergency, requiring prompt Most of the filtered calcium is reabsorb d · th
discontinuation of potassium-containing fluids and proximal tubule (70%), ascending loop of Henle (200~} ~
administration of medications that ensure stability of myo- the distal tubule and collecting duct (5-10%). Factor~ ~at
cardial membrane, intracellular shift of potassium and promote calcium reabsorption include parath
. . 't . ormone
enhance its elimination (Box 6.4). Continuous ECG moni- (PTH), ca lcitomn, vi amm D, thiazide diuretics and
I 11 II
volume deple?on. Volume expansion increased sodium bones. Decrease in extracellular calcium concentration,
intake and ~mretics such as manni~ol and frusemide stimulates the CaSR in parathyroid glands, resulting in
promote calcium excretion.
an increase in PTH secretion (Fig. 6.7). PTH increases
The intestine. serves as a Iong-term homeostatic . mecha- distal renal tubular reabsorption of calcium within
..~.,...
;c:m. for calcium. Although the maior . source of calcmm
. minutes and stimulates osteoclast activity, with release
15 dietary, less than 15% of dietary cal · · absorbed , of calcium from the skeleton within 1-2 hours. More
. . . h . cmm is
1
pnman Y m t e ileum and jejunum by means of active prolonged PTH elevation stimulates 1a-hydroxylase
transport and facilitated diffusion. Calcium is controlled activity in the proximal tubular cells, which leads to 1,
prima~ily ~y major regulatory hormones, PTH, calcitonin 25-dihydroxyvitamin D production. In the kidney,
and v1tamm D. Additionally thyroid hormones, growth vitamin D and PTH stimulate the activity of the epithelial
hormone, adrenal and gonadal steroids also have minor calcium channel and the calcium-binding protein (i.e.
influences on calcium metabolism. calbindin) to increase active transcellular calcium
Role of the calci~m-sensing receptor. The calcium-sensing absorption in the distal convoluted tubule. These
receptor (CaSR) is a G protein-coupled receptor, which mechanisms help to maintain normal levels of serum
allows the parathyroid chief cells, the thyroidal C cells
and the ascending limb of the loop of Henle (renal tubular
epithelial cells) to respond to changes in the extracellular
calcium concentration. The ability of the CaSR to sense
the serum calcium is essential for the appropriate
calcium.
Plasma calcium exists in three different forms: 50% as
biologically active ionized form, 45% bound to plasma
proteins (mainly albumin) and 5% complexed to phosphate
and citrate. In the absence of alkalosis or acidosis, the
I
I
regulation of PTH secretion by the parathyroid glands proportion of albumin-bound calcium remains relatively
and for the regulation of passive paracellular calcium constant. Metabolic acidosis leads to increased ionized
absorption in the loop of Henle. Calcitonin secretion and calcium from reduced protein binding and alkalosis has
renal tubular calcium reabsorption are directly regulated the opposite effect. Plasma calcium is tightly regulated
by the action of calcium ion on its receptor. Ionized despite its large movements across the gut, bone, kidney
calcium acts through calcitonin, to inhibit its release from and cells in the normal range of 9-11 mg/ dL.
7-dehydrocholesterol in
0 skin
I~
P
Dietary '
{i I
{frf'tf!_ ....__.... i_______,
Vit 0 2 (ergocalciferol)
Vit 0 3 (cholra1citero1)
Cholecalciferol (vitamin D)
~boo~tlo"
I
{ ~--- ~ from bones I
I Renal
I 24a-hydroxylase
\ \
('JI I
I
I
I
\ /
by kidneys
'' ' /
t
',,...,. .,. " "" 24,25-(0H)20 3
__ - "'' (inactive)
---
...
·,.
Rg. -6. 7• R ulation of plasma calcium. Reduction in Ionized calcium results In parathorrnone secretion, which through direct and
Indirect. egt
· ns on the bOnes, Intestine and the kidneys results In positive calcium balance. Calcttonln results In accretion of bone·
oc 10
rnass. Discontinuous lines Indicate 1n
hlbit ry control
° ':~ · ..
I - ,'i -
. -
... ' 1_f..1
, ; ..:..; , .
"'4· ... ._.. ~·· . .!.
78
Because calcium binds to albumin and only the unb0tmd Tabl~ 6.9: Caw;es of hypocalcemia ..
(free or ionized) calcium is biologically active, the semm level h rs after birth) or late (3-7
Neonatal: Early (within 48-72 ou . . prematurity; Infant of
must be adjusted for abnorrnal albumin levels. For every days alter birth) neonatal hypoc~lcom~a, hate milk
1 g / dl drop in semm albumin below 4 g/dL, measured diabetic mother; neonates fed high P asp
serum calcium decreases by 0.8 mg/dL. Corrected calcium . lasia of parathyroid glands,
can be calculated using the following formula: Parathyroid. Aplasla or hyp~p d h poparathyroidism·
DIGeorge syndrome, idiopathic;. ps~u o ytations of calciu~
Corrected Ca = autoimmune parathyroidltis; activating mu
[4-plasma albumin in g/dL] x 0.8 + measured serum calcium sensing receptors
Alternatively, serum free (ionized) calcium levels can Vitamin D:Deficiency; resistance to vitamin.D action; acquired
be directly measured, negating the need for correction for .or inherited disorders of vitamin D metabolism
albumin. Others: Hypomagnesemia; hyperphosphatemia (ex.cess inta~e'.
renal failure); malabsorption syndromes; metabolic alkalos1s,
Hypocalcemla
hypoproteinemia; acute pancreatitis
Hypocalcemia is defined as serum calcium less than
Drugs: Prolonged therapy with trusemlde, corticosteroid or
8 mg/ dL or ionized calcium below 4 mg/ dL. The causes
and algorithm for investigating the etiology are shown in phenytoin
Table 6.9 and Fig. 6.8. Hypocalcemia manifests as central
nervous system irritability and poor muscular contractility. Box. 6.5: Clinical features of hypocalcemla
Newborns present with nonspecific symptoms such as • Carpopedal and muscle spasms
• lethargy, poor feeding, jitteriness, vomiting, abdominal
• Tetany
distension and seizures. Children may develop seizures,
twitching, cramps and rarely laryngospasm (Box 6.5). • Laryngospasm
Tetany and signs of nerve irritability may manifest as • Paresthesias
muscular twitching, carpopedal spasm and stridor. Latent • Seizures
tetany can be diagnosed clinically by clinical maneuvers • Irritability, depression, psychosis
such as Chvostek sign (twitching of the orbicular.is oculi • Intracranial hypertension
and mouth elicited by tapping the facial nerve anterior to • Prolonged QTc interval
the external auditory meatus) and the Trousseau sign
Normal low
+ +
ls=e=ru=m= phc•o=s=ph=a=te:::\_ _ _ _ _ 1Correct hypomagnesemia
.--- - - --= J
+ +
Low
•
High
•
Parathormone 25(0H)D3 and 1,25(0HhD3 levels
Fig. 6.8: Algorithm for evaluation of hypocalcemla . .VDDR ~~min Dd~p~~~~~~ rt~.k~t~· :: ',."·:~.:., · :~;·:':-..
Fluid and Electrolyte Disturbances
,,------~-------------~~~=.::.::::.r.:::.=:~~=--~~~~~~- 119 -
(cnrpopcdnl spnsm elicited by inflating a blood pressure Table ~.10: C~uses ofhYperc~lcemia
cu ff on. .th' nrm to 'n 1)ress
r tu.e a b ave the systolic
· pressure
Neonates .
for 3 nun). ECG shows prolonged corrected QT interval
Neonatal primary hyperparathyroidism, secondary hyper-
(QTc~ to mor~ than 0.45 seconds. Cardiac function may be
parathyroldism
impaired be~a use of poor muscle contractility. Prolonged
Familial hypocalciuric hypercalcemia
hypocnlcerma can present with features of rickets. Excessive supplementation of calcium . . . . .
William syndrome, hypophosphatasia, 1d1opath1c infantile
Management
hypercalcemia
Tetany, laryngospasm and seizures must be treated
imm.e~iately with 2 ml/kg of 10% calcium gluconate, Older chlldren
admuustered IV slowly under cardiac monitoring. Calcium Hyperparathyroidism (parathyroi~ .adenom~, autoso~al
dominant hereditary hyperparathyro1d1sm, multiple endocrine
gluconate 10% (100 mg/ml) IV solution contains
9.8 mg/ml (0.45 mEq/ml) elemental calcium; calcium neoplasia type 1)
Malignancies: Non-Hodgkin or Hodgkin lymphoma, Ewing
chloride 10% (100 mg/ml) contains 27 mg/ml (1.4 mEq/
sarcoma, neuroblastoma, Langerhans cell histiocytosis,
mL). Initially, IV calcium boluses are given every 6 hr.
rhabdomyosarcoma
Thereafter, oral calcium supplementation is provided at
I
Granulomatous disease: Sarcoidosis, tuberculosis, Wegener
40-80 mg I kg Ida y. Oral ca lei um therapy is used in
disease, berylliosis
asymptomatic patients and as follow-up to intravenous
Others: Vitamin D or A intoxication; thiazide diuretics; milk-
(IV) calcium therapy. Intravenous infusion with cakium-
. alkali syndrome; dietary phosphate deficiency; subcutaneous
containing solutions can cause severe tissue necrosis; fat necrosis; thyrotoxicosis; prolonged immobilization
therefore, integrity of the IV site should be ascertained
before administering calcium through a peripheral vein. with epigastric pain and vomiting. Ectopic calcification can
Rapid infusion of calcium-containing solutions through manifest as conjunctivitis or band keratopathy. Renal
arterial lines can cause arterial spasm and if administered manifestations due to renal stones and nephrocalcino$is can
via an umbilical artery catheter, intestinal necrosis. progress to renal failure, and polyuria and polydipsia occur
Magnesium administration is necessary to correct any due to nephrogenic diabetes insipidus.
hypomagnesemia because hypocalcemia does not respond
until the low magnesium level is corrected. In patients Treatment
with concurrent acidemia, hypocakemia should be The initial treatment of hypercalcemia involves hydration
corrected first. Acidemia increases the ionized calcium to improve urinary calcium excretion. Rapid lowering of
levels by displacing calcium from albumin. If acidemia is serum calcium can be expected with isotonic sodium
corrected first ionized calcium levels decrease. chloride solution, because increasing sodium excretion
Calcium ca;bonate is an oral supplement providing 40% increases calcium excretion. Addition of a loop diuretic
elemental calcium. Therapy with cholecal.ci~erol is u~ed inhibits tubular reabsorption of calcium but attention
in patients with vitamin D deficiency. Cal~1tnol, an active should be paid to other electrolytes (e.g. magnesium,
metabolic form of vitamin D (i.e. 1, 25 -dihy~roxychole potassium) during saline diuresis. Bisphosphonates serve
calciferol), is administered in liver or renal disease. to block bone resorption and decrease serum calcium within
a couple of days but have not been used extensively in
Hypercalcemla children. Pamidronate and etidronate have been used in
. . defm'ed as a serum calcium level greater the treatment of hypercalcemia due to malignancy,
HYPerca1cerma is . 11 · immobilization and hyperparathyroidism but may cause
than 11 m /dL. Because calcium metabolis.m norm~ y is
tightly cogntrolled by. the b.ody,de;,;i: ;:- ~~spoet~~ee~~
1 mineralization defects. IV calcitonin may also be used with
bisphosphonates.
elevations should be investigate . f ltO g (Table 6.10). Peritoneal dialysis or h emodialysis can be used in
. b a e and other ac ors
calcem1a vary Y g ti' lthough it can cause extreme situations, particularly in patients with renal
HYPercalcem1a is 0 ften asymptoma /dL
. . c, a
and consistently at failure. Calcimimetics (cinacalcet hydrochloride) change the
s 1 ls as low as 12 mg
ymptoms at eve I dL Such high values are, however,
values above 15 mg d· presen t as stupor and coma · Box 6.6: Clinical features of hypercalcemia
rarely encountere d an ti' may have vomiting
Neonates may b e a~ymP toma .
c or
Clinicalfeaturesinolder
' Lethargy, confusion, . Br~dycardi~, ·systemi<; .. . j
hYPotonia hypertens1onorseizures. . cl d . 't bili'ty !.depression, "coma ,.
. · ·· hypertension, headache
. , . d in Box 6.6 and m u e irn a , ; H~oreflexia . · . _ Nephrocalcinosis, - · • :
dUJ.dren are summanze . teady gait and proximal o I ~ • ' I I . . . '"" ; 'II\
l .. .
80
U aves and prolonged QT
configuration of the CaSR in a manner that makes it more nonspecific T wave changes, w
sensitive to serum calcium. Surgical intervention may be interval and arrhythmias.
needed in patients with hyper-parathyroidism, particularly
with recurrent renal stones or serum calcium levels higher Treatment
ti nts with mild symptoms or
than 12.5 mg/ dL. Subtotal parathyroidectomy can be Therapy can be oral for pa. e e s ptoms or those
performed, or complete parathyroidectomy can be chosen intravenous for patients wit~ ~ever. o~evere hypoma-
with reimplantation of a small amount of tissue in the unable to tolerate oral adml.!llstrati . s fusion of
m
·
pH of body fluids is calculated using the Henderson- of disturbances occurs, the disorder is classified as a mixed
Hasselbach equation: acid-base disorder. The latter are suspected when the
compensation in a given patient differs from the predicted
pH= pK +log (HC03- /pC02]
values in Table 6.11.
where pK is the dissociation constant of the acid. In order to maintain body homeostasis, changes in pH
Alteration in either serum bicarbonate concentration or are resisted by a complex system of intracellular and extra-
the partial press~re of carbon dioxide causes acidosis (pH cellular buffers that reversibly bind hydrogen ions and
<7.35) o: alkalos1s (pH >7.45). Metabolic activity results in resist change in pH. In metabolic disorders, the
production of two types of acids, carbonic acid (a volatile extracellular buffers rapidly titrate the addition of strong
acid, derived from carbon dioxide) and nonvolatile acids acids or bases. Intracellular buffers chiefly accomplish the
(including sulfuric acid, organic acids, uric acid and buffering of respiratory disorders. Secondary respiratory
inorganic phosphates). Accumulation of H+ ions of compensations to metabolic acid-base disorders occur
nonvolatile acids due to excess production or inadequate within minutes and is completed by 12 to 24 hours. In
buffering, failure to excrete H+ or loss of bicarbonate results contrast, secondary metabolic compensation of respiratory
in metabolic acidosis. If the reverse occurs, it results in
metabolic alkalosis. The principle mechanism for carbon
dioxide handling is by the lungs. Hyperventilation results
in C02 washout and drop in arterial pC02 (respiratory
alkalosis), hypoventilation has the opposite effect
disorders begins more slowly and takes 2 to 5 days for
completion. The compensatory mechanisms do not return
the pH to normal until the underlying disease process has
been appropriately treated. Extracellular buffers include
bicarbonate and ammonia, whereas proteins and
I I
(respiratory acidosis). When only one primary acid-base phosphate act as intracellular buffers. Hemoglobin is a
abnormality occurs and its compensatory mechanisms are powerful intracellular buffer because its negatively
activated, the disorder is classified as simple acid-base charged histidine moieties accept H+, normalizing the pH.
disorder. A simple algorithm for defining simple acid- Other proteins also have negative charges that can accept
base disorders is shown in Fig. 6.9. When a combination H+.
I Blood pH I
I
Acidemia Alkalemia
(!pH) (t pH)
tHco;
J. Hco;
Metabolic acidosis
+
Respiratory alkalosis Metabolic alkalosis
Respiratory acidosis
with compensatory with compensatory with compensatory w ith compensatory
metabolic alkalosis respiratory alkalosis metabolic acidosis respiratory acidosis
+-- H. + Hco; ~
H{~}
H20+C02
Glutamlne
!(~
NH3 + Glutamate
t~.
"l
J
' I•
.. . _, •I '
I
I ....
.,
. ,.
'.: . ,
:.:.- ·~:... .·' ....~~·t·1.?:·,~.....~
.• ..... .:. .·. ·:
Fig. 6.10: Renal regulation of acid-base disorders. l = bicarbonate-carbonic acid buffer: 2 == monot)yd.roge~ ph~sphate·
dfhydrogen phosphate buffer; 3 = ammonia-ammonium buffer ·· · ·
-~---.-.,_..., _____
Fluid and Electrolyte Disturbances 83.
bonate. The accompanying unmeasured anion results in as in gastrointestinal or renal loss of bicarbonate or when
increased anion gap proportional to the fall in bicarbonate. hydrogen ions cannot be secreted because of renal failure)
In contrast, when the bicarbonate is lost from the body, no (Table 6.12). .
new anion is generated; therefore, there is a reciprocal Another useful tool in the evaluation of metabolic
increase in chloride ions (proportional to the fall in bicarbo- acidosis with normal anion gap is urinary anion gap.
nate) resulting in normal anion gap. Hypoalbuminemia is Urinary anion gap= urinary [Na•] + [K•] - [Cl-]
the most common cause of a low anion gap. Albumin
represents about half of the total unmeasured anion pool; Urinary anion gap is negativ~ in pati~nts wi~ diar:~ea
for every decrease of 1 g/ dL of plasma albumin, the plasma regardless of urinary pH, and unnary aruon gap is positive
anion gap decreases by 2.5 mEq/L. in renal tubular acidosis. An elevated osmolal gap (>20
mOsm/kg) with metabolic acidosis suggests the presence
Metabolic Acidosis of osmotically active agents such as methanol, ethylene
glycol or ethanol.
Metabolic acidosis is an acid-base disorder characterized
by a decrease in serum pH that results from either a loss Cllnlcal Features
I
in plasma bicarbonate concentration or an increase in
Initially patients with a metabolic acidosis develop a
hydrogen ion concentration (Table 6.12). Primary meta-
bolic acidosis is characterized by an arterial pH of less
compen~atory tachypnea and hyperpne~, which may
than 7.35 due to a decrease in plasma bicarbonate in the progress if the acidemia is severe, and the child can present
absence of an elevated PaC02. If the measured PaC02 is with significant work of breathing and distr~ss (Kussma~ I
breathing). An increase in H+ concentration results m
higher than the expected PaC02, a concomitant respiratory
pulmonary vasoconstriction, which raises pulmonary
acidosis is also present (caused by a depressed mental
artery pressure and pulmonary vasc.u lar res is tance.
state, airway obstruction or fatigue). Acutely, medullary
chemoreceptors compensate for metabolic acidosis Tachycardia is the most common card10vascular. ef~ect
seen with mild metabolic acidosis. Cerebral vasodilation
through increase in alveolar ventilation, which results in
occurs as a result of metabolic acidosis and may contribute
tachypnea and hyperpnea that washes off C0 2 and
corrects pH. to an increase in intracranial pressure. Acidosis shifts the
oxygen-hemoglobin dissociation curve to the right,
Calculation of plasma anion gap helps to classify decreasing hemoglobin's affinity for oxygen. During
metabolic acidosis into those with elevated anion gap (i.e. metabolic acidosis, excess hydrogen ions move toward the
>12 mEq/L as in increased acid production or decreased intracellular compartment and potassium moves out of the
losses) and those with normal anion gap (i.e. 8-12 mEq/L cell into the extracellular space. Untreated severe
metabolic acidosis may be associated with life-threatening
Tab-le 6.12: Causes of metabolic -acidosis arrhythmias, myocardial depression, respiratory muscle
Normal anion gap (hyperchloremic acidosis) fatigue, seizures, shock and multiorgan failure.
Renal loss of bicarbonate Treatment
Proximal (type 2) renal tubular acidosis. carbonic anhydrase
inhibitors (e.g. acetazolamide), tubular damage due to drugs It is important to identify the cause of metabolic acidosis
or toxins as most cases resolve with correction of the underlying
Gastrointestinal bicarbonate loss disorder. The role of alkali therapy in acute metabolic
Diarrhea, ureteral sigmoidostomy, rectourethral fistula, fistula acidosis is limited. It is definitely indicated in some
or drainage of small bowel or pancreas situations, e.g. salicylate poisoning, inborn errors of
Decreased renal hydrogen ion excretion metabolism, or in those with pH below or equal to 7.0 or
Renal tubular acidosis type 1 and type 4 (aldosterone [HC03-] less than 5 mEq/L, as severe acidosis can produce
deficiency) myocardial dysfunction. The amount of bicarbonate
Potassium sparing diuretics . required is
Increased hydrogen chloride production . .
Parenteral alimentation, increased catabohsm of lysine and Body weight (kg) x base deficit x 0.3.
arginine One mL of 7.5% sodium bicarbonate provides 0.9 mEq
Ammonium chloride ingestion bicarbonate. The recommendation is to replace only half
Elevated anion gap . of the total bicarbonate deficit during the first few hours
'd production/accumulation: Sepsis, shock,
of therapy. This amount is given as continuous infusion
Increase d act .
I · ·
poisonings (ethanol • methanol • ethylene glycol); inborn errors over two hours. Rapid correction of acidosis with sodium
! of metabolism . bicarbonate can lead to extracellular volume expansion,
Ketoacidosis: Diabetic ketoacidosis, starvation exacerbating pulmonary edema in patients with cardiac
.' Exogenous acids: Salicylates, iron, ison~azi~, paral~ehyde failure. In the latter, the rate of infusion should be slower.
l
~ ·1ure of a cid, excretion:
rat . . . Acute or chronic kidney disease. - If hypematremia is a concern, sodium bicarbonate may
be used as part of the maintenance intravenous solution.
84
olic alkalosis
During correction of acute metabolic acidosis, t~e effect Table 6.13: Causes of metab
of sodium bicarbonate in lowering serum potassium and Chloride responsive . )
ionized calcium concentrations must also be considered .. nasogastric drainage
Gastric fluid loss (e.g. vomiting, . . diuretics metolazone)
and monitored. Since bicarbonate therapy generates large Volume contraction (e.g. loop or thiazide '
amow1t of C0 2, ventilation should increase proportion- Congenital chloride diarrhea, villous adenoma
ately otherwise this might worsen intracellular acidosis.
Cystic fibrosis . . ventilated patients
The inability to compensate may be especially important Post-hypercapnia syndrome (mechanica11 Y
in patients with diabetic ketoacidosis who are at risk for with chronic lung disease)
cerebral edema. In diabetic ketoacidosis, insulin therapy
Chloride resistant
generally corrects the acidosis.
Primary aldosteronism (adenoma, hyperplasia)
In newborns, frequent administration of hypertonic Renovascular hypertension , renin secreting tumor
solutions such as sodium bicarbonate have led to intracranial
Bartter and Gitelman syndromes
hemorrhage resulting from hyperosmolality and resultant Apparent mineralocorticoid excess .
fluid shifts from the intracellular space. Children with Glucocorticoid remediable aldosteronism
inherited metabolic abnormalities, poisoning, or renal failure Congenital adrenal hyperplasia (11 ~- and 17a-hydroxylase
may require hemodialysis. deficiency)
Mild to moderate acidosis in renal failure or renal tubular Liddle syndrome
acidosis improves on oral alkali therapy, the dose being 0.5 Excess bicarbonate ingestion
to 2 mEq/kg/ day of bicarbonate in 3-4 divided doses. In
cases of acidosis due to volume depletion, the volume deficit seizures. Generalized weakness may be noted, if the patient
should be corrected. also has hypokalemia. Patients who develop metabolic
alkalosis from vomiting can have symptoms related to
Metabolic Alkalosis severe volume contraction, with signs of dehydration.
Metabolic alkalosis (pH >7.45) is an acid-base disturbance Although diarrhea typically produces a hyperchloremic
caused by elevation in the plasma bicarbonate (HC03) metabolic acidosis, diarrheal stools may rarely contain
concentration in the extracellular fluid that results from a significant amounts of chloride, as in the case of congenital
net loss of acid, net gain of base or loss of fluid with more chloride diarrhea. Children with this condition present at
chloride than bicarbonate. There are two types of birth with watery diarrhea, metabolic alkalosis, and hypo-
metabolic alkalosis classified based on the amount of volemia. Weight gain and hypertension may accompany
chloride in the urine, i.e. chloride-responsive or chloride metabolic alkalosis that results from a hypermineralo-
resistant (Table 6.13). Chloride-responsive metabolic corticoid state.
alkalosis shows urine chloride levels of less than 10 mEq/L
and is characterized by decreased ECF volume and low Treatment
serum chloride levels, such as occurs with vomiting or The overall prognosis in patients with metabolic alkalosis
use of diuretics. This type responds to administration of d~pends on the underlying etiology. Prognosis is good
chloride salt (usually as normal saline). Chloride-resistant with prompt treatment and avoidance of hypoxemia. Mild
metabolic alkalosis is characterized by urine chloride or ~oderate 1:'etabolic alkalosis or alkalemia rarely
levels of more than 20 mEq/L. Primary aldosteronism is reqmres correction. For severe metabolic alkalosis, therapy
an example of chloride-resistant metabolic alkalosis and should address the underlying disease state, in addition
this type resists administration of therapy with chloride. t~ moderating the ~lkalemia. The initial target pH and
The body compensates for metabolic alkalosis through bicarbonate level m correcting severe alkalemia are
buffering of excess bicarbonate and hypoventilation. Intra- approximate!~ 7.55 _and ~O mEq/L, respectively.
cellular buffering occurs through sodium-hydrogen and Therapy with diuretics (e.g. furosemide , th·iaz1·des )
. .
potassium-hydrogen ion exchange, with eventual h ld b d
s ou . e iscontinued. Chloride-responsive metabolic
formation of C02 and water from HC03. Within several alkalosis responds to volume resuscitation and ch1 ·d
hours, elevated levels of HC03 and metabolic alkalosis 1f Chi ·d · on e
rep edioifnfi. ul on e-resistan~ metabolic alkalosis may be
inhibit the respiratory center, resulting in hypoventilation more 1
c t to contro . As with correction of an lectr0 lyt
and increased pC02 levels. This mechanism produces 'd b imbal th · ye e
or aa li- a_se .thanthce, e goal is to prevent life-threatening
a rise in pC02 of as much as 0.7 to 1 mm Hg for each comp cations Wl e 1east amount of conection.
1 mEq/L increase in HC03. For persistent severe metabolic alkalosis in th ~
of fluid overload, wherein saline cannot be o-i·v e se . g
Cllnlca/ Features . o- en, cautious
use of HCl or ammoruum chloride may be c ·d d
Signs and symptoms observed with metabolic alkalosis
'd h .
A cetazo1arm e may e1p patients with chloride- onsi ere .
· t t
b li alk 1 · ·d d resIS an
usually relate to the specific disease process that caused the meta o c . alkosis p_ro~i e _GFR is adequate. Correction
acid-base disorder. Increased neuromuscular excitability of metabolic a a1os1s m patients with renal fail ·.
. d' . · .. .1 uremay
(e.g. from hypocalcemia), sometimes causes tetany or require hemo ia1ys1s or continu~us renal replacement
.
;-\ •'~,"}i~J\"a. ~ 'o\Lta· \~ •• .,;~~ ., • ;~ •• •. ; , ..:• •' .~ ".!:,~4~-·- __
- ,...., .,.,. ""-V_.."f.-~. ~·-- 4
.: ·. ;
:~~~~:--~
' . ,,_..4.
Chapter
7
·Nutrition
Vinod K Paul • Anuja Agarwala • Rakesh Lodha
86
Nutrition I a1 II
Protein quality: Food proteins differ in their nutritional • Unsaturated fatty acids (MUFAs ?nd P~FAs) have
quality depending on their amino acid profile and double bonds in cis or trans conf1gurahon. Dou~le
digestibility. Cereal grains are deficient in lysine, threonine bonds in cis configuration are nutritionally good, while
or tryptophan, whereas pulses are rich in lysine but are in trans configuration (trans fatty acids) are bad for
limited in sulfur-containing amino acids, mainly health. Thus trans fats are a type of unsaturated fa ts.
methionine. When cereals are taken in combination with These occur ~aturally in small quantity. Artificial trans
the pulses, the deficiency in one is made good by an excess fats are created when hydrogen is passed throu~h
in other; thereby improving the overall quality of proteins liquid vegetable oils to make them more so.hd
in food. ('vanaspati'). Such fats are used in household cooking
Egg protein has the highest nutritive value and is as well as in snack foods (packaged baked food,
therefore taken as the reference protein, and the value of samosas, mathris, kachoris, pizzas, burgers, French
others is expressed as relative to the egg (taken as 100%). fries, etc.). Trans fats increase the risk of coronary art~ry
Generally, animal proteins have a higher biological disease due, in part, by increasing levels of low density
value than the plant proteins. The nutritive value of a lipoproteins (LDL) and lowering high density
mixture of two proteins may be higher than the mean of lipoprotein (HDL). Hence, trans fat intake is best
the two because of mutual complementary effects. avoided.
• PUFAs are grouped into two series, namely, linoleic
Requirements: Nearly 10-12% of the total energy should acid (LA, C18:2n-6) and alpha-linolenic acid (ALA,
be provided from protein sources. An intake of 8% C18:3n-3} depending on the position of double bond.
proteins may be sufficient for food having a higher content
of animal proteins or high value proteins in the diet.
Fats
LA and ALA are long chain dietary essential fatty acids.
LA gets metabolized to arachidonic acid (AA), while
ALA to eicosapentaenoic acid (EPA), docosapentaenoic
l
acid (DPA) and docosahexaenoic acid (DHA).
Fats function as structural elements of the cell membranes, Medium chain triglycerides (MCT) are an immediate
act as vehicle for absorption and transport of fat-soluble source of energy as they are transported directly from the
vitamins (A, D, E and K) and are precursors of small intestine to liver by portal vein and burned
prostaglandins and hormones. Fats are made of fatty acids immediately to produce energy. MCT improves endurance
and dietary fats are mixture of largely triglycerides, small performance, promotes fat burning, spares muscle
proportion of phospholipids and cholesterol. glycogen, increases metabolic rate, maintains muscle mass
Fatty acids are classified into 3 groups: Saturated fatty acids and lowers blood cholesterol level. Supplementation with
(SFAs}, monounsaturated fatty acids (MUFAs) and MCT is used in the dietary management of cystic fibrosis,
polyunsaturated fatty acids (PUFAs}_ (Fig. 7.1~. _H umans obesity, pancreatic insufficiency, AIDS, epilepsy, gallstones,
can synthesize SFAs and MUFAs besides obtauung them high blood cholesterol levels, fat malabsorption, intestinal
from diet, but PUFAs cannot be synthesized in the body lymphangiectasia, and are used as energy supplements in
and have to be provided through diet. athletes. Sources of MCTs are coconut oil, palm kernel oil,
• Saturated fatty acids (SPA) consisting of straight, even butter (15% of MCT}. Prolonged use of MCTs alone leads
numbered chains of 4-24 carbon atoms. Th ey are to essential fatty acid (EFA) deficiency.
classified as short (C<lO), medium (C12:0 and C12:0) Long chain triglycerides (LCT} provide essential fatty
or long (C16:0-C24:0) chain fatty acids based on carbon acids (EFAs) and require carnitine to produce energy.
chain length. The degree of saturation determines MCI and LCT should be ideally used in combination to
whether the fat is solid or liquid at room temperature- prevent EFA deficiency.
more the saturation, harder and more solid is the fat.
Essential fatty acids (EFAs) cannot be synthesized in
the body and have to be supplied through dietary fat. EPA
Simple lipids J and DHA are important components of gray matter of
I
the brain and improve intellectual performance.
I Saturat ed fatty acids~ I Unsaturated fatty acids I Deficiency of EFA leads to cessation of growth, alopecia,
Ghee, butter, coconut oil diarrhea, impaired wound healing, decreased calcium
I absorption, decreased calcium deposits in bones and
... t
Monounsaturated fatty acids Polyunsaturated fatty acids decreased bone strength. It is recommended that ALA (n-
Olive oil, palm oil Corn oil, soya bean oil, 3 fatty acid) content of the diet should be about 0.5% of
groundnut oil, mustard oil sunflower oil
the total calories or 1.0-1.5 g/ day.
+
Essential fatty acids
Cholesterol is the component of cell membrane, helps
Llnoleic acid
the body produce steroid hormones and bile acids.
Linolenic acid
Requirements: Fats are major source of energy in diet. In
Fig. 7 .1: Classification of fats normally growing children, about 25-30% of energy intake
-88
should be derived from fat which includes 10-15%
invisible fat. However, in malnourished children, up to
Essential Pediatrics
· ments are calculated
body weights, the energy require
roughly as shown in Table 7.2.
45% of calories can be safely provided from fat.
DIETARY STANDARDS
Ittvisible fat: Fat present naturally in our food but cannot . h uirements of nutrients
be seen and separated from food such as milk and milk Infants and children have hig er req . t for maintainin ,
products, egg and meat, nuts contain good amount, while than adults. While adults need ~utn~~:nts and childre~
cereals, pulses, vegetables and fruits contain negligible constant body weight and functions, b t f
f aintenance u a1so or
amount. require _nutrients not o~lY or. m id rate of rowth and
promotmg and supporting their rap g
Visible fat: Fat which is used for cooking or added while development.
cooking such as edible vegetable oils and ghee. afe intake levels have been
A range of acceptable Or S . .
To provide a healthy balance of visible fat, daily diet established for almost all the important nutnents at ·
should provide <7% saturated fat, 10% polyunsaturated d i"fferen t ages, w h"ch
i are recognized as recommended T , •
fat and rest 13% should be derived from monounsaturated dietary allowances (RDA). ,,.
fats. A minimum of 3% energy should be derived from
linoleic acid and 0.3% from linolenic acid. Recommended Dietary Allowa nces (RDAs)
There is no single oil/fat with the ideal composition; it RDAs are nutrient specific and technical in nature. These
is recommended to use blend of two or more vegetable are formulated based on the current knowledge of
oils. nutritional requirements of different _age and_ sex groups
depending on anthropometry (weight, he~ght), ~o_dy
Energy composition, climate and environment, phystcal activity, . •'
Energy needs of children are computed keeping in mind physiological status and body demands: All the~e factors .~
the increase in body size, high metabolic rate that regulates lead to differences in food intake and nutnent reqwrements. . '.
body temperature and maintains high level of activities, Summary of Recommended Dietary Allowances (RDA) · .
and marked developmental changes in organ function and for energy and protein revised in 2010 is shown in
composition. Table 7.3.
Energy requirements vary through childhood because . "
of variations in growth rate and physical activity. Nutritive Value of Some Common Foods
Although growth rate slows in toddlers, their activity Table 7.4 portrays energy, protein, carbohydrates and fat
levels are high, and appetite and food intake tends to be composition of common Indian food items and portions.
erratic. In older children, growth is more constant but
energy needs vary within and between individuals.
During adolescence, energy needs increase due to rapid
growth and development. •Table 7.3: Daily eri.ergy and pr~tein requirements at diff;r~n~
There are three critical periods in early life of a young
child with regards to energy requirements: Around
.ages
Group Age Energy Protein
6 months when complementary feeding is initiated, (kca//d) (gld)
between 1 and 2 years when physical activity is increased Infants
'
Q-6 months 90 kcal/kg/d 1.2 glkg/d "'
and between 10 and 12 years for girls and 15-18 years for .,
6-12 months 80 kcal/kg/d 1.7 glkg/d
boys when puberty is attained.
· Calculation of energy requirement should account for
the level of physical activity and the energy required
Children 1-3 years
4-6 years
1050 17 .
1350 20 . I
allowing for optimal growth. For children with normal 7 - 9 years 1700 30 .• .
Boys 10-12 years 2200 '~h
40
· Tabl~ :2: Si~ple calc~iation of daily energy require~~nt; for ,
Girls 10-12 years
7 2000 40 .;- · -,-:~
'-~
Boys 13-15 years 2750
1
children 54
At 1O kg body weight 1000 kcal Girls 13-15 years 2300 52
Weight >10 kg- 20 kg 1000 kcal + 50 kcal for each kg Boys 16-17 years 3000
•:
62
above 1o kg, e.g. for a 15 kg child, Girls 16-17 years 2450 56
requirement will be 1250 kcal Adult male Sedentary 2300 60
Weight >20 kg 1500 kcal + 20 kcal for each kg Adult female Sedentary
above 1O kg, e.g. for a 30 kg child, · 1900 55
requirement will be approximately Adapted from Nutrient Requirements and Dietary :, :
Allowances for Indians, ICMR 201 0 [Val hRecommende~ doff at ·. :
1700 kcal l •· • ..,
places) ues ave been roun e
•.! I '
Nutrition 89 I
·- .-...- ...... __ _, ___ ~--..... -- -
... ......
...._......_ -- __ .,.. '*.
Table 7.4: Approximate nutritive value of common food Items .
Food items Raw edible Household Energy Protein Carbohydrate Fat·
amount measures (cooked) (kcal) (g) (g) (g)
(g ormL) or portion
Milk and milk products
Human milk 100 ml 65 1.1 7.4 3.4
Milk (cow) 100 ml Y2 glass 73 3.2 4.9 4.4
Milk (buffalo) 100 ml Y2 glass 107 3.6 8.3 6.5
Paneer (home made-cow milk) 30 g 1 small piece 76.5 5.5 3.5 4.5
Curd (homemade-cow milk) 100 ml 1 small cup 62 3.2 3.2 4.0
Meat and poultry
Chicken, thigh, skinless 100 g 1 serving 200 18.0 14.0
Meat (flesh} 100 g 4 pieces 135 20.0 6.0
Fish (rohu) . 100 g 2-3 pieces 100 20.0 2.4
Egg whole (hen) 45 g 1 No. 74 5.0 6.0
Egg white (from 1 egg) 25 g 11 4.0 0.01
Egg yolk (from 1 egg) 20 g 60 3.2 5.2
Cereals and millets
Chapati 25 g wheat flour 1 medium size 80 2.5 16.0 0.3
Bread (white)
Wheat daliya/suji/sevian
Rice
Biscuits
Cake
30 g maida
25 g raw
25 g raw
10 9
30 9
1 big slice
1 katori cooked
1 katori cooked
2 nos
1 small piece
72
80
90
50
129
2.5
2.5
2.0
1.0
1.8
14.5
16.0
19.5
7.0
18.0
0.5
0.3
0.1
2.0
5.5
I
Sago/arrowrooVcorn flour 25 g 5 tsp 88 22.0
Millet grains (bajra, jowar, jau, 25 g 5 tsp 94 3.0 16.0 2.0
oats, kottu, etc.)
Khichri [raw rice 20 g plus 25 g raw 1 katori cooked 85 3.0 18.0 0.1
raw dal 5 g (4:1)] (100 g)
Pulses
Dhooli dais (moong/arhar, etc.) 25 g raw 1 katori 80 6.0 14.0 0.3
Sabut dais (Rajma/Chana, etc.)
Soyabean (white)
25 g raw
25 g raw l cooked
(100-125 g)
70
95
5.0
10.0
10.0
2.5
1.0
5.0
Vegetables
100 to 125 g Y2 katori cooked 25 2.0 2.5 0.6
Green leafy and seasonal
vegetables (spinach, bathua,
bhindi, cauliflower, beans, etc.)
100 g 1 small size 60 1.5 13.0 0.2
Root vegetables (includes arbi,
potato, zimikand, etc.)
100 g 1 katori 80 7.0 13.0 0.1
Peas fresh 1.7 0.13
100 g Y2 katori 10 0.53
Low carb vegetables (Lauki/
tori/ tinda/kaddu/cucumber)
·' (Contd... )
Ill 90 Essentlal Pediatrics -......
·--··-, -··- - · -"
T~bla 7 4· Approxl~ate -,,utrrtlv~ ~1-;;e of common food lt~ms (Cont
d --~
...
) ·~1 :
Carbohydrate Fat · 1 ·
• •Raw edible Household measures Energy Protein I•.•
Food Items (g) ··'
(g)
amount (cooked) or (kcal) (g)
(g ormL) portion
Sugars
Sugar 5g 1 levelled tsp 20 5.0
Honey/jam 5g 1 levelled tsp 16 4.0
Jaggery 5g 1 tsp 18 4.5
Drinks
Sugarcane juice 100 ml Y2 glass 60 15.0
0.2 3.0 0.1
Coconut water 100 ml Y2 glass 14
Soft drinks 100 ml Y2 glass 37 9.2
I Toned milk
Double toned milk
Skimmed milk
Dahi (plain)/Curd
Buttermilk (lassi-plain)
100 ml
100 ml
100 ml
100 mL
100 mL
Y2 glass
Y2 glass
Y2 glass
1 cup
Y2 glass
58
48
33
75
32
3.2
3.0
3.0
3.7
2.0
4.5
5.0
5.0
5.0
2.0
3.0
2.0
4.5
2.0
Sweet lassi 100 mL Y2 glass 95 2.5 15.5 2.5
Salted lassi 100 mL Y2 glass 32 1.8 2.0 1.8
Cottage c~eese 30 g 1 small pc 93 5.5 0.7 7.5
Ice cream 100 ml 1 small cup 180 4.0 23.0 8.0
Ice cream (sugar free) 100 mL 1 small cup 113 5.0 12.0 5.0
kcal· Kilocalories; tsp: Tea spoon
NB: .Some approximations made In values of nutrient contents
Adapted from:
1 Indian Food Composition tables, NIN, ICMR, 2017 . . 017
2: Compilation of Food Exchange list (Technical series 6), Lady Irwin College, Deihl Un1vers1ty, 2
3. For processed foods, nutritional facts are taken from the packets
BALANCED DIET or more food items from each of these groups is essential
to label a diet as 'balanced'.
Balanced diet is defined as nutritionally adequate and
appropriate intake of food items that provide .all the The nutrient characteristics of common foods are
nutrients in required amounts and proper proportions, to depicted in Table 7.5. "-I-
ensure normal growth, development and disease f~ee Cereals, millets and pulses are the major source of most
optimum health amongst children and adolescents. Wide nutrients in Indian diet. Milk provides good quality
variety and combination of foods are used to formula~e protein and calcium and hence is an essential item of our
balanced diet for various categories of people to meet their diet. Eggs, flesh foods and fish enhance the quality of diet
needs as per nutritional standards (RDA). . but Indians are predominantly vegetarian society and
In order to plan nutritionally adequate balanced diet most of our nutrients are derived from cereal/pulse and
as per RDA, "food group system" is used. that con.verts milk based diets. Oils and nuts are calorie rich foods and
quantitative nutrient data into food-based information. are useful in increasing the calorie density. Vegetables and
Based on major content of nutrients, foods_ are fruits provide protective substances such as vitamins,
minerals, fiber and antioxidants.
conventionally placed into 5 groups: (i) Cereal~'. -~ets
and cereal grains; (ii) Pulses, legumes and nuts; (m) Milk, In a normal balanced Indian diet, recommend~d macro~
egg and flesh foods; (iv) Vegetables and fruits; (~) Fats nutrients as a proportion of total energy intake should be:
and sugar. Food groups differ in their nutrient quality and carbohydrates (55-?0%), fats (25-30%) and proteins
quantity and hence while planning a diet, inclusion of one (10-12%).
Nutrition 1 91 •
----~
Table 7.5: Nutritional- charac teristics of common food Items
Foods Main nutrients Other characteristics
Milk and milk products Protein, fat, calcium, phosphorus, Provide high quality protein lactose and saturated fats; lack
vitamin 8 2 in iron and vitamin C
Egg (hen) Protein, fat, phosphorus, riboflavin Provide high quality protein and vitamin 8 12 ; lacks in
carbohydrates and vitamin C; contains saturated fats
and is rich in cholesterol
Chicken Protein, phosphorus Provides high quality protein and all B vitamins; does not
provide carbohydrate, fat and Iron
Fish Protein, fat, calcium, vitamin 8 12 Lacks in carbohydrates; good source of high quality protein and
fat containing omega-3 fatty acids
Cereals grains and Carbohydrate, fiber, folic acid, Good source of energy; has poor quality protein that lacks in
products vitamins 8 1 and 8 2 , phytates, iron lysine; provides negligible amounts of unsaturated fat; phytates
hinder the absorption of iron
Pulses, peas, beans Carbohydrate, protein, folio acid, Good source of energy; contain proteins of lower quality that
calcium, fiber, vitamins 8 1 and 8 2 , lack in methionine; provides negligible amount of unsaturated
iron, phosphorus fat; absorption of iron is hindered by phytates
Soya bean Protein (35%), fiber, fat (40%), Source of high quality protein (twice of that in pulses) and
calcium, iron, zinc, copper, fat (three times that in pulses); contains polyunsaturated,
magnesium, selenium, folic acid, monounsaturated and saturated fats; vegetarian source of
Seasonal vegetables
NORMAL BALANCED DIET FOR VARIOUS AGE GROUPS for breastfeeding and complementary feeding are given
in Table 7.6.
Exclusive Breastfeeding (Q-6 months of age)
An infant should be exclusively breastfed till six months Between 6 and 12 months, child goes through a major
of age. During this phase, additional food or fluids are food transition that depends on several cardinal factors,
essential to be considered in feeding the child.
not required as breast milk is nutritionally complete for
the child's growth and development; it protects from
infections and strengthens immune system. Breastfeeding Factors to be Considered while
issues are discussed in Chapter 8. Planning Food for Young Child
Energy density: Most of our traditional foods are bulky
Complementary Feeding [6 months onwards) and a child cannot eat large quantities at a time. Children
After six months of age, breast milk alone is not enough have low stomach capacity. Hence, it is important to give
to make an infant grow well. Complementary feeding small energy-dense feeds at frequent intervals to ensure
refers to food which complements breast milk and ensures adequate energy intakes by the child.
that the child continues to have enough energy, protein Energy density of foods given to infants and young
and other nutrients to grow normally. children can be increased without increasing the bulk by
Complementary feeding is started six months of age adding:
(180 days), while continuing breastfeeding. • Oil or ghee: Fat is a concentrated source of energy and
Breastfeeding is encouraged up to two years of age or increases energy content of food without increasing the
more in addition with normal food. Key recommendations bulk. The false belief that a young child cannot digest
• 92 Essential Pediatrics
I
milk, or sevian, dalia, halwa or kheer prepared in milk or any cereal porridge cooked in milk, or mashed
boiled/fried potatoes
Frequency: 3-5 times a day
Offer banana, biscuit, cheeku, mango or papaya as snacks In between the servings
Remember: Sit by the side of child and help him to finish the serving; wash your child's hands with soap
and water every time before feeding
2 years and older Give family food as 3-4 meals each day
Twice daily, also give nutritious snacks between meals, e.g. banana, biscuit, cheeku, mango, or papaya
Remember: Ensure that the child finishes the serving; teach your child to wash his hands with soap and
water every time before feeding
fat is not true. A young infant can digest fat present in to ensure intakes of all macronutrients and micro-
breast milk as well as all other foods like cereals and nutrients.
pulses. Sugar and jaggery are also rich in energy though
not as high in calories as fat but can easily be added in Amount off eed: At 6 months of age, feed should be started
infant foods. with small amount as much as 1-2 teaspoons and the
quantity is increased gradually as the child gets older and
• Thickening the gruel: Thin gruels do not provide enough
starts to accept food better. Child should be given time to
energy. A young infant particularly during 6-9 months
adapt gradually to larger quantities from teaspoon to table
requires thick but smooth mixtures. For instance, spoon and then to a katori.
advising dal ka paani as a complementary food recipe is
absurd. Infant should be given medium thickness gruel Consistency of f eed: Infants can eat pureed, mashed and
of 'dal' with added oil instead. semi-solid foods beginning at six months. By 8 months,
• Amylase rich foods (ARF) such as malted foods reduce most infants can also eat "finger foods" (snacks that can
the viscosity of the foods and therefore the child can be eaten by children alone). By 12 months, most children
eat more quantities at a time. (Malting is germinating can eat the same types of foods as consumed by the rest
whole grain cereal or pulse, drying and then grinding). of the family. As the child grows older, he should be
shifted to more appropriate foods suitable for his age. Help
Often the energy needs of the child are not well
children to accept the usual family food gradually which
appreciated by caregivers. A child between the age of is safely prepared and fed.
1 or two years of age needs as musch as 50% the nutrition
required by an adult. Frequency offeediltg: An average healthy breastfed infant
needs complementary foods 3-4 times per day at 6-8
Nutrient density of the feed can be ensured by including months of age and 3-4 times per day at 9-11 months and
a variety of foods in order to meet all the nutrients. Even 4-5 times at 12-24 months of age, with additional
as early as 9 months, infants need small portions of food nutritious snacks such as a piece of fruit, offered 1-2 times
items from all food groups to be included in their diet per day or as desired. Snacks are defined as foods eaten
Nutrition · 193 -
between meals, usually convenient and easy to prepare. In this chapter, we will focus on undemutrition among
If energy density or amount of food per meal is low, or children less than 5 years of age.
the child is no longer breastfed, more frequent meals may
be required. Consequences of Undernutrltlon
Undernourished children have higher risk of infections and
Hygiene: Good hygiene and proper food handling should mortality. Undernutritlon is associated with 35% of under-5 child
be practiced to prevent children from infections and deaths. Undernutrition is strongly associated with shorter adult
malnutrition. Simple hygiene practices include: (a) Washing height, poor lean weight, less schooling, low cognition, reduced
hands before food preparation and eating, (b) Serving economic productivity and, for women, lower offspring
freshly cooked foods (cooked should not be kept for 2- birthweight. Low blrthweight and undernutrition in childhood
3 hour.s), (c) Using clean utensils and covered properly, are important risk factors for diabetes mellltus, hypertension
(d) Using clean cups and bowls when feeding children, and dyslipidemlas In adulthood.
and (e) Avoiding use of feeding bottles.
Underweight, Stunting and Wasting
Planning Diet for Individual Child
Undemutrition has three subgroups: Underweight, wasting
In clinical practice, it is imperative to plan diets for and stunting (Table 7.8 and Fig. 7.2)
different conditions among children with various ages, An underweight child has low-weight-for-age. It means
both healthy and sick. In this exercise, it is important to that the weight of this child is less than minus 2 standard
ensure the right balance of macronutrients and food deviations (-2SD) on the WHO Growth Standard for her/
groups. A sample diet plan for 1000 kcal is shown in his age. An underweight child could be wasted or stunted,
Table 7.7. This can serve as a template to plan diets of or both.
lower or higher energy content by varying amounts of
ingredients. Stunting denotes low-height-for-age. The height (or length)
of a stunted child is below minus 2 standard deviations
UNDERNUTRITION ( <- 2SD) at her /his age on the WHO Growth Standard. A
stunted child is short for her /his age. Stunting indicates
Undernutrition is a set of conditions that result from chronic undernutrition.
inadequate consumption, poor accretion or excessive loss
of nutrients. Overnutrition includes overweight and Wasting implies low-weight-for-height. A child whose
obesity, and is caused by overindulgence or excessive weight for her /his actual height is less than minus 2
intake of nutrients, or pathological conditions. standard deviations (<-2SD) at her / his age on the WHO
Malnutrition refers to deficiencies, excesses or Growth Standard has wasting. A wasted child has a thin
imbalances in a person's intake of energy and/ or nutrients appearance. Wasting indicates acute undemutrition as
(WHO). Thus, malnutrition connotes both undernutrition result of recent food deficit or an acute illness such as
as well as ovemutrition. In practice, however, often the diarrhea.
terms malnutrition and protein energy malnutrition (PEM) Growth charts based on WHO Growth Reference
are used interchangeably with undernutrition. Standards are given in Chapter 2.
1oookcal
Table 7~7: A sample, baianced diet pla'n ba.sed on the food..measures. The food portions are to bes pread over 24 hours .
·_in multiple meals· and ~nacks · · · 1
• ·• • • ' :, • · • I
Food Amount/ready to eat portion Energy (kcal) Protein (g)
Cow's milk/curd 1 glass milk (200 ml) plus Y2 katori curd (50 ml milk) 180 8.0
Pulses 25 g raw dal (1 katori cooked ) 80 6.0
Cereals wheat/rice 100 g
4 chapatis (100 g wheat flour) OR
2 chapatis (50 g wheat flour) plus 2 katoris rice cooked (50 g grain) OR
2 chapatis (50 g wheat flour) plus 1 katori cooked suji (25 g wheat flour)
plus 1 katori rice cooked (25 gm raw grain) 340 9-10 g
Vegetables 150 g
Green/seasonal 100 g (1 katori cooked) 25 2.0
Potato 50 g (1/2 katorl cooked)) 30 1.0 ! ... ~
Normal height - - - - -
------------------ 60%
~ •• l
50%
40%
30%
20%
10%
0%
Underweight Stunting
Normal Wasted Stunted •2005--05 •2015-16
(thin) (short)
Fig. 7.3: Trends In undernutritlon In India: proportion of under-5
Fig. 7.2: Appearance of undernourished children
children with underweight, stunting and wasting . Source:
National Family Health Surveys 3 (2005-06) and 4 (2015-16)]
C/assifica tion Criteria As per WHO Sub-classification As per WHO Reference Standards
growth standards Moderate underweight Weight-for-age below minus
Underweight Low-weight-for-age Weight-for-age less than 2 SD and up to minus 3 SD (<-2 SD
minus 2 SD (<-2 SD) to -3 SD)
Severe underweight Weight-for-age minus 3 SD (<-3 SD)
Stunting Low-height* (or length) Height*-for-age less than Moderate stunting Height*-for-age below minus 2 SD
for-age minus 2 SD (<-2 SD) and up to minus 3 SD (<-2 SD to
-3 SD)
Severe stunting Height*-for-age below minus
3 SD (<-3 SD)
Wasting Low-weight-for-height Weight-for-height less Moderate wasting Weight-for-height below minus
than minus 2 SD 2 SD and up to minus
(<-2 SD) 3 SD (<-2 SD to -3 SD)
Severe wasting Weight-for-height below minus
3 SD (<-3 SD)
*'Length ' in the first two years of life
SD: Standard deviation
The term 'edematous malnutrition' is used if edema is During the first six months of life, 20-30% of children
also present in an underweight child. Clinical classification are alr~ady ~demourished, often because they were born
of undernutrition as marasmus, kwashiorkor and low brrthwe1ght. The proportion of undernutrition and
marasmic kwashiorkor is also helpful (discussed below). stunting starts rising after 4-6 months of age (Fig. 7.4).
After 6 months of ~ge, breast milk alone is not enough to
Epldemlology meet the energy reqlllrement of the child, and therefore solid
Childhood undemutrition is an underlying cause in an food (complementary feeding) must be introduced, in addition
estimated 45% of all deaths among under-5 children. to continuing breastfeeding. 'This often does not happen.
According to the National Family Health Survey (NFHS) It is estimated that only 10% of children between the
4, carried out in 2015-16, 36% of India's children under age of 6-24 months have adequate nutritional intake
the age of five are underweight, 38% are shrnted and 21 % (NFHS 4). Most children in the country are thus 'nutrition
are wasted (Fig. 7.3). Comparable figures for 20054>6 were hungry' in this critical phase of life. In addition the child
43%, 48% and 20%, respectively. There has been a slow becomes more prone of ~fections, particularly diarrhea,
reduction in undemutrition in the country over the years, due as she becomes mobile and puts unhygienic objects
especially stunting. Yet we continue to have the highest into mouth and ingests unhygienic food products.
burden of childhood undemutrition in the world. Late introdu:tion of complementary feeding and
Undemutrition rates are highest among the scheduled inadequate fo~~ intake leads to ~creasing predisposition
tribes and scheduled caste families. Proportion of to undernutr1tlon. The proportion of children who are
underweight children in rural areas (38%) is higher than stunted or underweight increases rapidly with the child's
urban areas (29%). age until about 18-24 months of age (Fig. 7.4).
Nutrition 195 -
60
1
c:
!!:! 1
:!:! 30
:.cu
ff!.
20 WJfOOffil}LJl 1rl I\ I!ii Ii !
10
iI , - ~ l lrlrHITTiff .ttfffiffit:0il :
0 UillJJJ~l~Lll1ll,~~JJ1! UU !LlU., - ! I\I!J !
0 2 4 6 8
-!
10 12 14 16 16 20 22 24 26 26 30 32 34 36 36 40 42 44 46 46 50 52 54 56 56
!_:
I
Age in months
Fig. 7.4: Proportion of malnourished children according to age (National Famlly Health Survey 4. 2015-16)
Importance offetal life and the first two years of life (the first Three cardinal determinants of undernutrition
1000 days 'window') for linear and brain growth. 1. Low birth weight: Infants born small often remain
Length at 2 years is the predictor of adult height and undernourished. About 20% childhood undernutrition is
productivity. Brain achieves a near adult size by two years attributable to fetal growth restriction.
of age. It is practically impossible to reverse the height 2. Infections: Diarrhea, pneumonia and other infections consume
and brain growth deficit after 2 years of age with nutrition energy and hamper growth. Diarrhea causes nutrient loss in
and other interventions; it is simply too late. stools. About 25% childhood undernutrition is attributable to
diarrhea, pneumonia and other infections.
Thus, nutrition during the first 1000 days since
3.Low food intake: Inadequate breastfeeding, delayed
conception, encompassing pregnancy and the first 2 two
complementary feeding and insufficient food intake means
years of life, is of profound importance for realizing the less energy and protein available for growth. This underlies
physical and intellectual potential. Nutritional corrections about 55% of childhood undernutrition. ·
after two years will not change these outcomes.
Hence, ensuring optimum nutrition of the mother Clinical Syndromes of Undernutrltlon
before and during pregnancy, and optimum feeding of Moderate and severe malnutrition is associated with one
children in the first 2 years of life (including breastfeeding of classical syndromes, namely, marasmus, kwashiorkor,
for first 2 years, and adequate solid feeding after 6 months or with manifestations of both. Another classification, the
of age) is absolutely crucial in human life. severe acute malnutrition (SAM) is used in the program
setting.
Determinants
The causes of malnutrition could be viewed as immediate, Marasmus
underlying and basic as depicted in Fig. 7.5. Marasmus is characterized by severe form of wasting.
The immediate determinants of a child's nutritional There is marked wasting of fat and muscle as these tissues
status work at the individual level. These include low are consumed to make energy. Acute starvation or acute
birthweight, illnesses (particularly infections such as illness over a borderline nutritional status precipitates this
diarrhea and pneumonia) and inadequate dietary intake. form of undernutrition. Sever marasmus is a typical form
Finally, the underlying determinants are influenced by of severe acute malnutrition (SAM).
the basic determinants. These include the socioeconomic • The main sign is severe wasting. The child appears very
status and education level of the families, women's thin (skin and bones) and has no fat. There is severe
empowerment, cultural taboos regarding food and health, wasting of the shoulders, arms, buttocks and thighs
access to water and sanitation, etc. Access to safe water (Fig. 7.6).
and sanitation, will reduce a significant proportion of • The loss of buccal pad of fat creates the aged or wrinkled
undernutrition. appearance that has been referred to as monkey fades
- 96
Nutritional status
Immediate
Low birth weight determinants
Health environment
Underlying
Household food Care for mothers
security and services
determinants
and children
t
Resources for food security Resources for care Resources for health
!POVERTY !
....
I
Political and economic structure \ Basic
I Sociocultural environment determinants
Kwashlorkor
Uncommon in India now, it usually affects children aged
1-4 years. The main sign is pitting edema, usually starting
in the legs and feet and spreading, in more advanced cases,
to the hands and face. Because of edema, children with
kwashiorkor may look healthy so that their parents view
them as well fed.
• General appearance: Child may have a fat sugar baby
appearance.
• Edema: It ranges from mild to gross and may represent
up to 5-20% of the body weight.
• Muscle wasting: It is always present. The child is often
weak, hypotonic and unable to stand or walk.
• Skin changes: The skin lesions consist of increased
pigmentation, desquamation and dyspigmentation.
Pigmentation may be confluent resembling flaky paint
or in individual enamel spots. The distribution is
typically on buttocks, perineum and upper thigh.
Petechiae may be seen over abdomen. Outer layers of
skin may peel off and ulceration may occur. The lesions
may sometimes resemble burns. Fig. 7.6: A child with se~ere acute malnutrition. Note the
• M11co11s membrane lesions: Smooth tongue, cheilosis and (a) dull, lustreless, sparse hair; temporal hollowing; loss of buccal
angular stomatitis are common. Herpes simplex pad of fat; anxious look; (b) Loose folds of skin In the gluteal
stomatitis may also be seen. region giving a 'baggy pant' appearance . .
Nutrition I 91 II
• JI11ir: Changes include dyspigmentation, loss of managed in hospital. The management of low birth weight
characteristic curls and sparseness over temple and infants is discussed in Chapter 8.
occipital regions. Hair lose their lustre and are easily
pluckable. A flag sign which is the alternate bands of Miid and Moderate Malnutrition
hypopigmented and normally pigmented hair pattern Mild and moderate malnutrition make up the greatest
is seen when the growth of child occurs in spurts. portion of malnourished children and account for >80%
• ~~11lnf .c11n 11~es: Incl~des unhappiness, apathy or of malnutrition associated deaths. It is, therefore, vital to
1~ntab1hty with sad, intermittent cry. They show no intervene in children with mild and moderate malnutrition
signs of hunger and it is difficult to feed them. at the community level before they develop complications.
• Ne11rological clln11ges: Changes such as tremors are seen The mainstay of treatment is provision of adequate amounts
during recovery. of protein and energy; at least 150 kcal/kg/day should be given.
• Gnst roi11lesti11nl system: Anorexia, sometimes with Nutritious home food is recommended. The ICDS
vomiting, is the rule . Abdominal distension is programme provides extra ration for such children.
ch.aracteristic. Stools may be watery or semisolid, bulky In order to achieve these high energy intakes, frequent
with a low pH and may contain unabsorbed sugars. feeding (up to seven times a day) is often necessary.
• /\11e111in: Nutritional anemia is almost always associated. Because energy is so important and because carbohydrate
• Cardiovnsc11lnr system: The findings include cold, pale energy sources are bulky, oil is usually used to increase
extremities due to circulatory insufficiency and are the energy in therapeutic diets. Nutrient-dense foods
associated with prolonged circulation time, bradycardia, enable children to consume and maximize the absorption
diminished cardiac output and hypotension. of nutrients in order to fulfil their requirements of energy
I
• f{e11nl function: Glomerular filtration and renal plasma and all essential nutrients.
flow are diminished. There is aminoaciduria and According to WHO, animal-source foods are more
inefficient excretion of acid load. likely to meet the amino acid and other nutrient needs of
recovering children. Milk and eggs are excellent animal
Morasmlc Kwoshlorkor origin foods for children. Plant-source foods, in particular
It is a mixed form of undernutrition and manifests as legumes or a combination of cereals and legumes, also
edema occurring in children who may or may not have have high-quality proteins, although they may also
contain some anti-nutrients such as phytates, tannins or
other signs of kwashiorkor and have varied manifestations
inhibitors of digestive enzymes, which may limit the
of marasmus.
absorption of some micronutrients, particularly minerals.
Severe Acute Malnutrition (SAM) It is recognized increasingly that a relatively small
increase over normal protein requirements is sufficient
This special classification is recommended by WHO for for rapid catchup growth, provided energy intake is high.
identifying and managing children with life thre~t~ning A protein intake of 3 g!kg/day is sufficient. Milk is the most
undernutrition in public health programme settmgs. frequent source of the protein used in therapeutic diets,
Children with SAM have a mix of features of marasmus though other sources, including vegetable protein
and kwashiorkor. mixtures, have been used successfully. Adequate minerals
Severe acute malnutrition (SAM) among children and vitamins should be provided for the appropriate
6-59 months of age is defined by WHO and UNICEF as duration. The best measure of the efficacy of treatment of mild
any of the following three criteria: . . and moderate malnutrition is weight gain.
i. Weight-for-height below -3 standard deviation
(<-3SD) on the WHO Growth Standard; or Severe Acute Malnutrition (SAM):
Children 6 to 59 Months
ii. Presence of bipedal edema; or
iii. Mid upper arm circumference (MUAC) below 11.5 cm. The World Health Organization has developed guidelines
In a child below 6 months of age, the MUAC is not used for the management of severe acute malnutrition (SAM)
and these have been updated in 2013. Guidelines are
as a criterion.
Children with SAM have a high risk of death. In mainly for children of more than 6 months of age.
addition to debilitating undemutrition, they o.ften ha~e Once a child, 6 months or older, is diagnosed as SAM,
serious infections such as diarrhea, pneumorua, se~sis, she/he should be thoroughly assessed by a physician for
malaria and skin infections. They require urgent attention. complications by looking for severe edema(+++), lack of
appetite, medical complications on clinical examination
(e.g. severe anemia, pneumonia, diarrhea, dehydration,
~ANAGEMENT OF MALNUTRITION cerebral palsy, tuberculosis, HIV, heart .disease. etc.) and
The management o f malnu tr1.ti'on depends on its severity. danger signs according to IMNCI a~g~nthm (Fig. ~.7). If
While mild to moderate malnutrition can be managed on any of these are present, it is cla.ss1fie.d as complicated
ambulatory basis, severe malnutrition is preferably SAM, and the child is referred for inpatient management.
- 98
·
Mainstay of home managem
ent is nutritional
Th' uld b
-
rehabilitation with high energy foo~. alls ~~ailabl:
,I '
months of age
adequate home foods prepared form oc Y
Presence of
1. Weight-for-height below -3 standard deviation cereals and pulses sugar, 01.1, mi'lk and/ or deggs etc.
(<-3SD) on the WHO Growth Standard; OR .
ensuring 175 cal/kg ' body we1g · ht/day · Rea y to use
2. Presence of bipedal edema; OR therapeutic food (RUTF), w 1ch a voids cumbersome
. h' .
3. Mid-upper arm circumference (MUAC) below . of recipes
.
11.5 cm (age 6 mo or more) preparation at h ome is · a practical option.. The
.
available .
evidence shows t h a t reco very rates are higher
i
Assess for the following complications
with RUTF than home food based regimens even when
families are well supported. . . .
RUTF is an energy dense, mineral and vitamin ennched
1. Servere edema(+++); OR food that has greatly improved the management of SAM.
2. Low appetite (failed appetite test), OR The composition of RUTF is shown in Table 7.9. The RUTF
3. Medical complications, OR
4. One or more danger sign as per IMNCI is made of peanut paste, sugar, milk solids and vegetable
oil with added minerals and vitamins. RUTF has a pas~,
I smooth consistency, and good taste. It is easy for the child
... t to eat and digest. RUTF can be locally produced or be
No Yes
commercially available. .
i i Caregiver should wash hands an? uten~ils use~ f~r
Uncomplicated SAM Complicated SAM feeding. Breastfeeding should be continued, if th~ child is
breastfed. The caregiver lovingly engages the child, talks
Supervised home Inpatient management to her, plays with her and makes feeding exercis~ an
management in a facility interactive affair. In addition, the child should be provided
Fig. 7.7: Approach to child with severe acute malnutrition sensory stimulation (play, physical activity, laughter,
exposure to colors and shapes, storytelling, massage, etc.).
If the above mentioned signs are absent, the child has Optimum home management of a child with SAM is
uncomplicated SAM and can be managed in the outpatient not possible without effective support by the health
setting with care at home (Fig. 7.7). Good appetite is worker. Families will invariably need close facilitation and
critically important in home care of the child with SAM guidance by the health worker (ASHA ANM or AWW).
because oral intake of adequate energy dense food is the A home contact every day initially, and then twice a week
fundamental requirement for recovery. is essential (Panel 1).
Supervised Home Management of Uncomplicated SAM The child should be monitored by health workers for
signs of undemutrition (weight, height, MUAC, edema,
Children with uncomplicated SAM can be managed at anemia, etc.) every week.
home provided: In addition to nutrition, every child on SAM treatment
• Family is counseled and fully engaged. should receive the following interventions: an antibiotic
• Community health worker(s) and peer counselors are course (amoxicillin for 5 days), mega dose of vitamin
involved to support the family. (100 000 units) in the presence of clinical deficiency
• Supply of adequate home food and ready to use (xerophthalmia, Bitot's spots or keratomalacia), and
therapeutic food (RUTF), if possible. albendazole single dose (for children over 2 years of age).
• Periodic monitoring for growth and medical condition (It may be noted that RUTF contains appropriate
can be ensured. supplements of minerals and vitamins). The child should
-Table 7.9: Composition and nutriti~n value of th'07tandard ready to u.se t~e~apeutlc fo~-(~UTF)_
Composition Food value per 100 g
Peanut paste 30% Energy 543 kcal
Sugar 29% Nutrients
Milk solids 20% Protein 15 g
Vegetable oil 18% Lipids 35 g
With added mineral mix1, vitamin mix2 , emulsifier and antioxidant Carbohydrates 43 g ., :..:1
1
Minerals per 100 g: Calcium 400 mg, phosphorus 400 mg, potassium 1100 mg, magnesium 110 mg, sodium <290 mg, iron 10 mg, zinc 12 mg,
copper 1.5 m, iodine 100 µg, selenlum 30 µg. . . . .
2Vitamins per 100 g: vitamin A 0.9 mg, vitamin 0 3 18 µg, vitamin K 21 µg, vitamin E 27 µg, vitamin C 54 mg, vitamin B, 0.5 mg, vitamin 8 1.8 mg,
2
vitamin 8 6 0.7 mg, vitamin 8 12 1.6 µg, niacin 5.8 mg, Ca-D pantothenate 3 mg, follc acid 225 µg, biotin 70 µg. · _
Nutrition 99 .
Ptmel 1: Summary of suporvlsod homo mnnagomon\ of n child Managomont of Compllcatod SAM In Hospital
with uncomplicated SAM All children ,.vllh compllcoled SAM should be hospltnllzed.
I. Nutrition thoropy The govomment hns cstnblished nutrlllon rehnbilltntion
• Whst to feed. lnltlnlly homo foods or RUTF; lntor homo cenh-cs (NRCs) In nil states.
foods. Continue breastfeeding
The child with severe mnlnutrltlon hns n complex
• How tnllch to feed: EMugh to provide HS kcal/l<g/dny bnckdrop with dlclnry, Infective, soclnl nnd economic
• How often to feed: 6-8 tlmos a day
focl'Ors underlyin~ the mnlnutrltion. A history of events
• How to feed: Lovingly, actively; ensuring hygiene
II. Other treatments
lending to the child's ndmlssion should be obtnined.
Socioeconomic history nnd fomily circumstnnccs should
• Oral amoxiclllln tor s days
be explored to underslnnd the underlying nnd bnsic
• Mega dose vitamin A, lf obvious signs of vitamin A deficiency
cnuses. Pnrtlculnr ntlention should be givm lo: Diet (before
• Albendazole 400 mg single dose
the current illness) including brenstfceding. Malnutrition
• Age appropriate vaccines
111. Sensory stimulation mny be the presentntion of HIV infection.
• Play, physical activity, Interaction Physicnl fonl ures of mnlnutrition ns described nbove
IV. Supervision and support should be lookL'd for. Following clinical features should
• Home visits by health workers, Initially dally, later twice a be pnrticularly looked for: Fever, hypothermia (temperature
week: more If necessary <35.5°C), signs of dehydmtion, shock (cold hands, slow
• Involve a peer counselor, a volunteer woman friend/
neighbor to support the f amity
• Ensure supply of RUTF
V. Monitoring by health workers (ASHA/AWW/ANM)
• Assess Intake, solve feeding Issues
cnpillnry rdill, wenk and rapid pulse), anemia, eye signs
of vitamin A deficiency, localizing signs of infections
(pneumonia, skin infections, diarrhea, tuberculosis), signs
of HIV infection, mouth ulcers and skin changes of
kwashiorkor.
I
• Evaluate for medical problems; treaVref er The general treatment involves 10 steps in two phases:
• Assess growth weekly
• The initial stabilization plrnsc focuses on restoring
be provided all the due vaccines as per national imn.mnizn- homeostasis and treating medical complications and
tion schedule. usually takes 2-7 days of inpatient treatment.
Nutritional rehabilitation of a child with SAM would • The rel111bilitntio11 pl1nse focuses on rebuilding wasted
require 3-5 months. Hence, home contacts are extremely tissues and may take several weeks.
important. After completion of treatment, the child should The 10 essential steps and the time frame are shown in
be followed up in the Anganwadi regularly. Fig. 7.8 and Table 7.10.
1. Hypoglycemia
2. Hypothermia
3. Dehydration
4. Electrolytes
5. Infection
No Iron With Iron
6. Mlcronutrlents
7. Initiate feeding
B. Catch-up growth
9. Sensory stlmulatlon
10. Prepare for follow-up
fig. 7.8: nie time frame for Initiating and achieving l O steps
- 100 1 Essential Pediatrics
..............
Table 7.10: Summary.of the management.of severe· malnutrttlon
. '
Hypoglycemia Blood glucose level <54 mg/dL or 3 mmol/L
If blood glucose cannot be measured, assume hypoglycemia
Hypoglycemia, hypothermia and Infection generally occur as a triad
Treatment
Asymptomatic hypoglycemia .
Give 50 ml of 10% glucose or sucrose solution orally or by nasogastrlc tube followed by first feed
Feed with starter F-75 every 2 hourly day and night
Symptomatic hypoglycemia
Give 10% dextrose IV 5 ml/kg
Follow with 50 ml of 10% dextrose or sucrose solution by nasogastrlc tube
Feed with starter F-75 every 2 hourly day and night
Start appropriate antibiotics
Prevention
Feed 2 hourly starting immediately
Prevent hypothermia
Hypothermia Rectal temperature less than <35.5°C or 95.5°F or axillary temperature less than 35°C or 95°F
Always measure blood glucose and screen for infections in the presence of hypothermia
Treatment
Clothe the child with warm clothes; ensure that the head Is also covered with a scarf or cap
Provide heat using overhead warmer, skin contact or heat convector
Avoid rapid rewarming as this may lead to disequilibrium
Feed the child immediately
Give appropriate antibiotics
Prevention
Place the child's bed in a draught free area
Always keep the child well covered; ensure that head is also covered well
May place the child in contact with the mother's bare chest or abdomen (skin-to-skin)
Feed the child 2 hourly starting immediately after admission
Dehydration Difficult to estimate dehydration status accurately in the severely malnourished child
Assume that all severely malnourished children with watery diarrhea have some dehydration
Low blood volume (hypovolemia) can coexist with edema
Treatment
Use reduced osmolarity ORS with potassium supplements for rehydration and maintenance
Amount depends upon how much the child wants, volume of stool loss, and whether the child Is vomiting
Initiate feeding within two to three hours of starting rehydration; use F-75 formula on alternate
hours along with reduced osmolarity ORS
Be alert for signs of overhydration
Prevention
Give reduced osmolarity ORS at 5-10 mUkg after each watery stool, to replace stool losses
If breastfed, continue breastfeeding
Initiate refeeding with starter F-75 formula
Electrolytes Give supplemental potassium at 3--4 mEq/kg/day for at least 2 weeks
On day 1, give 50% magnesium sulfate (equivalent to 4 mEq/mL) IM once (0.3 mUkg; maximum of 2 ml)
Thereafter, give extra magnesium (0.8-1 .2 mEq/kg dally) ·
Excess body sodium exists even though the plasma sodium may be low; decrease salt in diet
Infection Multiple infections are common; assume serious Infection and treat
Usual signs of infection such as fever are often absent
Majority of bloodstream infections are due to gram-negative bacteria
Hypoglycemia and hypothermia are markers of severe infection
Treatment
Treat with parenteral ampiclllln 50 mg/ kg/dose 6 hourly for at least 2 days followed by oral
a~oxlclllln 15 mg/kg 8 hourly for 5 days; and gentamicln 7.5 mg/kg or amikacl_n 15-20 mg/kg IM or IV once
daily for 7 days •'- "
"
(Contd...)
........ 1t .,.••
. Table' 7.10: Su-~mary of the management of severe malnutrition. (C--;,ntd..) •. , . ~-· .. - --·· ':--;
If nolmprove~ent occ~rs within 48 ·hours, change to IV cefotaxime (100-150 mg/kg/day s-8 hou~ly)
or
ceftrlaxone (50-75 mg/kg/day 12 hourly)
If other specific Infections are Identified, give appropriate antibiotics
Prevention
Follow standard precautions like hand hygiene
Give measles vaccine, If the child Is >6 months and not Immunized, or If the child is >9 months and had
oeen vaccinated before the age of 9 months
Mlcronutrlents Use up to twice the recommended dally allowance of various vitamins and minerals
On day 1, give vitamin A orally (If age >1 year, give 2 lakh IU; age 6-12 months, give 1 lakh IU; age
0-5 months, give 50,000 IU)
F~llc acid 1 mg/day (give 5 mg on day 1)
Zinc 2 mg/kg/day
Copper 0.2-0.3 mg/kg/day
Iron 3 mg/kg/day, once child starts gaining weight; after the stabilization phase
Initiate feeding Start feeding as soon as possible as frequent small feeds
If unable to take orally, initiate nasogastric feeds
Total. fluid recommended is 130 mUkg/day; reduce to 100 mUkg/day, if there is severe edema
Continue breastfeeding ad lib/tum
Start with F-75 starter feeds every 2 hourly
If persistent diarrhea, give a cereal based low lactose F-75 diet as starter diet
If diarrhea continues on low lactose diets give, F-75 lactose free diets (rarely needed)
Catch-up growth Once appetite returns in 2-3 days, encourage higher intakes
incre.ase volume offered at each feed and decrease the frequency of feeds to 6 feeds per day
Continue breastfeeding ad libitum
Make a gradual transition from F-75 to F-100 diet
Increase calories to 150-200 kcal/kg/day, and proteins to 4-6 g/kg/day
Add complementary foods as soon as possible to prepare the child for home foods at discharge
Sensory stimulation A cheerful, stimulating environment
Age appropriate structured play therapy for at least 15-30 min/day
Age appropriate physical activity as soon as the child is well enough
Tender loving care
Prepare for follow-up Primary failure to respond is indicated by:
Failure to regain appetite by day 4
Failure to start losing edema by day 4
Presence of edema on day 10
Failure to gain at least 5 g/kg/day by day 10
Secondary failure to respond Is indicated by:
Failure to gain at least 5 g/kg/day for consecutive days during the rehabilitation phase .
which can be dangerous nnd mny lend to hcnrt follurn. Rhwtod nl 0.3- 0.!3 mllq/kg/hr lnfu!llon of potl\!1!1lt1tn
In case ?f signs of ov~rhydrntion, ORS should bo stopped chlorlclo In lnlrnvcnow1 fh1ldt1, profornbly wllh conllnuous
immediately and child reassessed nftel' one hour. On lhu monltorlnH of lhu ECG.
other hand a decrease in the heart rntc nnd resplrntory Oncl! 1wvc1·c hypok11lcrnln IH corrected, nil severely
rate (if increased initially) and incrcni:;c In the urlm~ mnlnourll'lhcd chlldrnn ncl•d 1mpplcmcnll\I potu1:1slum nt
output indicate that rehydration is proceeding. Thu 3-'l mBq/kH/dny for nl lcnHt 2 wcckH. Potns1:1lum con be
return of tears, a moist oral mucosa, less sunken cyc:-1 given nR Hyt·up polrHlHlum chloride; the common
and fontanelle and improved skin turgor iue nl~o prcpnrnllon nvnllnblc lmR 20 mEq of potm1Hlurn/15 mL.
indica~ors o~ rehydra.tion. Once nny fom signs of On dny 1, 50% mngncHlum Hulfotc (cqulvnlont to
hydration (child less tlursty, passing urine, tcnrs, moist 1l mEq/mL) Rhould be given nt 0.3 mL/kg ton maximum
oral mucosa, eyes less sunken, foster skin pinch) nrc of 2 mL lntrnmusculnrly. Thcrcaftur, 0.8-1.2 mEq/kg
present, ORS for rehydration must be stopped nnd mngneslum should be given ornlly as n supplement mixed
continued to replace the ongoing losses.
with feeds.
··;·vcre deltydra tio11 witl1 sl1ock: It is important to recognize
severe dehydration in malnourished children. Severe Step 5: Treat/Prevent /nfeotlon
dehydration with shock is treated with intravenous fluids. Infection mny not produce the classlcnl signs of fever and
ideally, Ringer lactate with 5% dextrose should be used tnchycardia In severely malnourished children. Instead,
:is rehydrating fluid. If not available, half normnl saline severe infection mny be nssoclntcd with hypothermia.
tN/2) with 5% dextrose or Ringer lactate alone can be Locnllzing signs of Infection are often absent. The most
used. After providing supplemental oxygen, the common sites for infeclion nre the skin, the alimentary
rehydrating fluid should be given at a slow infusion rate trnct, the rcsplrntory tract (Including the cars, nose and
of 15 mL/kg over the first hour with continuous throat) and the urinnry trnct. Majority of the infections
monitoring of pulse rate, volume, respiratory rate, and septicemia arc caused by gram-ncgntlve organisms.
capillary refill time and urine output. Therefore, all severely malnourished children should be
If there is improvement (pulse slows, faster capillary assumed to have a serious infection on their arrival in
refill) at the end of the first hour of IV fluid infusion, n hospital. In addition, hypoglycemia and hypothermia are
diagnosis of severe dehydration with shock should be considered mnrkers of severe infection in children.
considered and the rehydrating fluid repeated at the same The following investigntions arc done for identifying
rate of 15 mL/kg over the next hour. This should be infections: (i) Hb, TLC, DLC, periphernl smear, (ii)
followed by reduced osmolarity ORS at 5-10 mL/kg/hr, urinalysis rmd culture, (iii) blood culture, (iv) chest X-ray,
either orally or by nasogastric tube. Patients should be (v) Mantoux test, (vi) gastric aspirate for AFB, (vii)
monitored for features of overhydration and cardiac peripheral smear for malnria (in endemic areas), and (viii)
decompensation. CSF examination (if meningitis is suspected).
All children with suspected infection should be treated
Septic slrock: If at the end of the first h~ur of 1y with broad spectrum parenteral antibiotics; ampicillin and
rehydration, there is no improvement or w~rsemng, sephc gentamicin or nmikacin (Table 7.11). Antimalarial and
shock must be considered and appropriate treatment anti tuberculous treatment should only be given when the
started. particular conditions are diagnosed.
Response to treatment will be indicated by resolution
Step 4: Correct Electrolyte Imbalance of initial symptoms and signs of infection, if any.
In severely malnourished children excess body sodium The child's activity, interaction with parents and appetite
exists even though the plasma sodium may be l?w. should improve . If there is no improvement or
Sodium intake should be restricted to p~e~~nt sodium deterioration of the symptoms/signs of infection, the
overload and water retention during the imtial p~a~e of child should be screened for infection with resistant
treatment. Excess sodium in the diet may precipitate bacterial pathogens, tuberculosis, HIV and unusual
pathogens.
congestive cardiac failure. , . .
!nourished children have def1c1enc1es
All severe1y ma . . h ma take two weeks Prcvc11tio11 of lwspit"l "cq11ired i11fcctio11: The health care
of potassium and magnesium, whic uris:ed children may personnel should follow standard precautions. The
or more to correct. Severely ma~~· ically manifest with effectiveness of hand hygiene should be emphasized to
develop severe hypo~alemia an cm ven res irator all health care providers, attendants and patients. It is
Weakness of abdominal, skeletal.dand e lysis tlectrf- essential that adequate safety measures nre taken to
· · ic flacci para ·
rnusc1es. This may mim . T waves inversion prevent the spread of hospital acquired Infections, since
cardiography may show ST depress1~:;;ssium is <2 mEq/L these children are nt hlgher risk of acquiring infections
and presence of U waves. If serum P ction should be due to their compromised immune status.
or <3.5 mEq/L with ECG changes, corre
- 104 1
Essential Pediatrics
No obvious infections or Oral cotrimoxazole (5 mg/kg 12houri~ of trlmethoprim) or oral amoxicillin 1O mg/kg
complications 8 hourly for 5 days · ·
Infected child or complications IV ampicillin 50 mg/kg/doses hourly and IV gentamicin 5-7 mg/kg/day in 1-2 do.ses; add ,
IV cloxacillin 100 mg/kg/day 6 hourly if staphylococcal infection is suspected; revise .: ,,.
therapy based on the culture sensitivity report
For septic shock or no Add third generation cephalosporin, I.e. IV cefotaxlme 100 mg/kg/day 8 hourly
improvement or worsening
Meningitis in initial 48 hr IV cefotaxime 200 mg/kg/day IV 6 hourly with IV amikacin 15 mg/kg/day 1-2 doses
Dysentery Ciprofloxacin 20 mg/kg/day in 2 divided doses; IV ceftrlaxone 50 mg/kg/day 12 hourly, if
child is sick or has already received nalidixic acid
Step 6: Correct Mlcronutrlent Deficiencies less than 4 g/dL or between 4 and 6 g/dL but with
respiratory distress, a blood transfusion should be given
All severely malnourished children have vitamin and
with whole blood 10 mL/kg bodyweight slowly over
mineral deficiencies. Micronutrients should be used as an
3 hours. Furosemide should be given at the start of the
adj~nct to treatment in safe and effective doses. Up to
transfusion. If the severely anemic child has signs of
twice the recommended daily allowance of various
cardiac failure, packed cells rather than whole blood
vitamins and minerals should be used. Although anemia
is common, iron should not be given initially due to danger should be transfused.
of promoting free radical generation and bacterial The hemoglobin concentration may fall during the first
proliferation. It should be added only after a week of week of treatment. This is normal and no transfusion
therapy when the child has a good appetite and starts should be given. In mild to moderate anemia, iron should
gaining weight. be given for two months to replete iron stores but this
Vitamin A deficiency is not an infrequent association should not be started until after the initial stabilization
and is an important cause of blindness caused by phase has been completed.
keratomalacia. Vitamin A should therefore be given to all
severely malnourished children on day 1 at 50,000 IU, Step 7: Initiate Refeedlng
100,000 IU and 200,000 IU for infants 0-5 month, 6-12 Feeding should be started as soon as possible with a diet
months and children>1 year of age unless there is definite which has osmolarity less than 350 mOsm/L; lactose not
evidence that a dose has been given in the last month. In more than 2-3 g/kg/day; appropriate renal solute load
presence of xerophthalmia, the same dose should be (urinary osmolarity <600 mOsm/L); initial percentage of
repeated on the next day and 2 weeks later. Children
ca~ories fr~m protein of 5%; adequate bioavailability of
>1 year but weighing <8 kg should receive half the age m1cronutrients and low viscosity. The preparation should
related dose . In presence of clinical evidence of be easy to prepare and socially acceptable and there
xerophthalmia the administration of vitamin A should be
sho~ld b~ facilities for adequate storage, cookin and ·
considered an emergency as the changes may progress to refrigeration. g
keratomalacia within hours. i·
Children with SAM receiving F-75, F-100 or RUTF Start cautious feeding: The suggested starter formulae '."
complying with WHO specifications do not need vitamin are u~u.ally ~mlk based, such as starter F-75 diet .
A supplementation because these preparations already (contammgw1th75kcal/100mL)
f · · Thep ro t. .
em content is ·.•
contain sufficient vitamin A. 0.9 go protem/100 ~L. Feeding should be started with ...
Vitamin K should be administered in a single dose of ~-75 as soon as possible as. frequent small feeds. If child . ··,
1
2.5 mg intramuscularly at the time of admission. Daily is unable to take orally with a cup a d
multivitamin supplements containing thiamine 0.5 mg/ 80°/. f h · n spoon or takes
~ .. ot od tB e tarfgetd~ntake, nasogastric feeds should be . '
1000 kcal, riboflavin 0.6 mg/1000 kcal and nicotinic acid miha e . reast ee mg should be continued . . .,
(niacin equivalents) 6.6 mg/1000 kcal should be given. It Older children could be started on ad hbttum. d
is better to give a formulation that is truly multivitamin (Table 7.12). cerea1 based diets
·'
(e.g. one that has vitamin A, C, D, E and Bd. Folic acid One should begin with 80 kcal/k Ida · · ;·
1 mg/ day (5 mg on day 1), zinc 2 mg/kg/ day and copper increas~ to 100 kcal/kg/day. To Jfill
~and gradually .. ~
0.2-0.3 mg/kg/ day should be given daily. Iron 3 mg/kg/ start with 2 hourly feeds of 11 mL/k I fe s, 0 1,le should ·.·
day should be added once child starts gaining weight, after are essential. The volume of fe d ? ed. Nightdfeeds
e s are increased ally ,
,
the stabilization phase. while decreasing the frequency of ad . . g~a u ·
Emergency treatment of severe anemia: If a severely · · d nl ministration The
ca1ones are mcrease o y after the child ·
malnourished child has severe anemia with a hemoglobin increased volume of feeds. can accept the
Nutrition
\105 -
Step 8: Achieve Catch-up GrONfh with F-100 Diet and RUTF offered 200 mL/kg/day of F-100 diet. Brea~tfeeding
For catch-up growth, energy and protein intake has to be should be continued Ad libitum.
enhanced further; F-75 diet (F-75 kcal/100 mL) would not Once the child achieves rapid weight gain, F-100 should
be enough. Starter F-75 feeds should be gradually replaced be changed to RUTF and gradually to home food.
with feeds which have a higher calorie density (100 kcal/ The daily amount of RUTF to be consumed varies
100 mL) and have at least 2.5-3.0 g protein/100 mL. These according to body weight as follows: 3--4.9 kg: 105-130 g;
feeds are called F-100 diets or Catch-up diets (Table 7.13). ~.9 kg: 200-260 g; 7-9.9 kg: 260--400 g and 10-14.9 kg:
Once appetite returns, increasing intakes of F-100 400--460 g. This amount is to be given along with plenty
should be encouraged. It is recommended that each of water in 2-3 hourly feeds. The child should continue to
receive other foods and breastfeeding during medical
successive feed is increased by 10 mL until some is left
nutrition therapy with RUTF.
uneaten. The frequency of feeds gradually decreased to
Home foods should be added as soon as possible to
6 feeds/ day and the volume increased till the child is being
prepare the child for home foods at discharge. They should
have comparable energy and protein concentrations once
Table 7.13: Catchup "diets
,) .. the catchup diets are well tolerated. Khichri, dalia, banana,
Diet contents F-100 F-100 curd-rice and other culturally acceptable and locally
Catch-up Catch-up
(per 100 mL) available diets can also be offered liberally.
(cereal based)
75
Special diets for diarr11ea: For children with persistent
Cow milk/toned dairy milk (ml) 95 diarrhea, who do not tolerate low lactose diets, lactose
(1/2)
(approximate measure of one katori) (3/4) free diet can be started. In these diets, carbohydrates (rice,
5 2.5
Sugar (g) sugar and glucose) can be given in varying proportions
(1) (1/2)
(approximate measure of one according to the patients' individual tolerance to achieve
level teaspoon) optimal balance between osmolarity and digestibility.
7
Cereal: Puffed rice (g) (2) Monitoring progress d11ri11g treatment: If there is a good
(approximate measure of one
weight gain of >10 g/kg/day, the same treatment should
level teaspoon) 2
2 be continued till recovery. If there is a moderate weight
Vegetable oil (g) . (1/2)
(1/2) gain of 5-10 g/kg/day; food intake should be checked
(approximate measure of one
and the children should be screened for systemic infection.
level teaspoon) 100 In case of poor weight gain of <5 g/kg/ day possible causes
100
Water to make (ml) 100 like inadequate feeding, untreated infection, psychological
101
Energy (kcal) 2.9 problems and coexisting infections like tuberculosis and
2.9
Protein (g) 3 HIV should be looked for and managed appropriately.
3.8
Lactose (g)
Ill 106 I ~~~~~~~~~----~=Es~s~e~nt~la~l!P~e~dl~at~rl~c~s~~~~------------------~--
step 9: Provide Sensory Stimulation and
. . .
a. Any senous c1mica 1con 1 1
d't'on or medical complication -
ld
Emotional Support as outlined for mfants w h o are 6 months of age or o er
. .
Delayed mental and behavioral development often occurs with severe acute malnutrition;
in severe malnutrition. In addition to the above b. Recent weight loss or failure to gain wei?~t; . (·
management, one should encourage a cheerful, c. Ineffective feeding (attachment, po~th?nmg ~nd _
stimulating environment; structured play therapy for at suckling) directly observed for 15-20 mm, ideally ma
least 15-30 min/ day; physical activity as soon as the child supervised separated area;
is well enough and tender loving care. d. Any pitting edema; . .
e. Any medical or social issue needing more. det~1.led
Step 10: Prepare for Follow-up assessment or intensive support (e.g. d1sab1hty,
Ideally, 6-8 weeks of hospitalization is required for depression of the caregiver, or other adverse social
optimum recovery. SAM children admitted to hospital can circumstances);
be transferred to outpatient care when their medical Infants less than 6 months of age with SAM should
complications have settled, edema, is resolving and they receive the same general medical care as infants with
have a good appetite, they are consuming adequate RUTF, severe acute malnutrition who are 6 months of age or
and are clinically well and alert. older:
The decision to transfer children from inpatient to a. Infants with severe acute malnutrition who are
outpatient care should be determined by their clinical admitted for inpatient care should be given parenteral
condition and not on the basis of specific anthropometric antibiotics to treat possible sepsis and appropriate
outcomes such as a specific mid-upper arm circumference treatment for other medical complications such as
I or weight-for-height/length.
National guidelines recommend treatment for
helminthic infections should be given to all children with
SAM before discharge. Give a single oral dose of
Albendazole 200 mg of for children aged 12-23 months,
tuberculosis, HIV, surgical conditions or disability;
b. Infants with severe acute malnutrition who are not
admitted should receive a course of broad-spectrum
oral antibiotic, such as amoxicillin, in an appropriately
weight adjusted dose.
400 mg for children aged 24 months or older. Feeding approaches for infants who are less than
6 months of age with severe acute malnutrition should
Post-Discharge Care at Home prioritize establishing, or re-establishing, effective
A child with SAM may be considered to have completed exclusive breastfeeding by the mother.
treatment when: Infants who are admitted:
• There is no edema for at least 2 weeks, plus a. Should be breastfed where possible and the mothers
• Weight-for-height (or length) reaches -2 SD or higher should be supported to breastfeed the infants. If an
on WHO Growth Standard or mid-upper-arm infant is not breastfed, support should be given to the
circumference is more than 12.5 cm mother to re-lactate
After discharge, the principles of care are the same for b. Should also be provided a supplementary feed:
supervised home care of uncomplicated SAM (as above). supplementary suckling approaches should, where
This is a very important phase and full support needs to feasible, be prioritized; for infants with severe acute
be extended to the family by involving the frontline malnutrition but no edema, expressed breast milk
workers and community. The treatment of the child is not should be given, and, where this is not possible,
complete till the weight-for-height and MUAC reaches commercial (generic) infant formula or F-75 or diluted
normal range (see below). F-100 may be given (prepared F-100 should be further
The caregiver should be advised to bring child back diluted by adding 30% water), eith er alone or as the
for regular follow-up checks, ensure booster immuni- supplementary feed together with breast milk; and for
zations, make sure that vitamin A is given every 6 months, infants with severe acute malnutrition and edema,
feed frequently with energy and nutrient dense foods and infant formula or F-75 should be given as a supplement
give structured play therapy. to breast milk;
Until the above is reached, the child must be under c. Should not be given undiluted F-lOOatanytime (owing
constant care at hospital and/ or home by a frontline health to the hig~ renal solute load and risk of hypematremic
team. Support to the family must be continued during this dehydration); prepared F-100 should be further diluted
phase and after discharge from treatment. by adding 30% water.
d. If there is no realistic prospect of being breastfed should
Severe Acute Malnutrition: Under 6 Months of Age be given appropriate and adequate replaceme~t feeds
Infants less than 6 months of age with SAM and any of such as commercial (generic) infant formula, with
the following complicating factors should be admitted for relevant support to enable safe preparation and use,
inpatient care: including at h ome when discharged.
Nutrition 1101 111
e. Assessment of the physical and mental health status of Panel 2: Preventing undernutrition In children
mothers or caregivers should be promoted and relevant
Individual Level Action
treatment or support provided
Mother
Infants less than 6 months of age with SAM and have
• Care of the adolescent girl
been admitted to inpatient care can be transferred to
outpatient care when: • Childbirth after 20 years
• Spacing between pregnancies
a. All clinical conditions or medical complications,
• No more than 2 children
including edema, are resolved, and • Iron and folic acid to ensure good hemoglobin
b. The infant has good appetite, is clinically well and alert, • Antenatal checks as per national program
and
• Additional food and micronutrients (especially Iron and folic
c. Weight gain on either exclusive breastfeeding or acid) in pregnancy
repl~cement feeding is satisfactory, e.g. above the
Child
median of the WHO growth velocity standards or more
• Initiation of breastfeeding within one hour
than 5 g/kg/ day for at least 3 successive days, and
• Exclusive breastfeeding for first 6 months, continuing till
d. The infant has been checked for immunizations and 2 years or more
other routine interventions, and • Special support to low birth weight babies for breastfeeding
e. The mother or caregiver is linked with needed and kangaroo mother care
community-based follow-up and support • Complementary feeding introduction at 6 months
For infants who are less than 6 months of age with • Optimum intake of food that is balanced, energy-dense and
severe acute malnutrition and who do not require of good quality
inpatient care, or whose caregivers decline admission for
assessment and treatment:
a. Counseling and support for optimal infant and young
child feeding should be provided, based on general
recommendations for feeding infants and young
• Hygiene, handwashing
• Full immunization especially, measles, BCG, rotavirus,
H. influenzae and pneumococcal
• Prompt treatment of diarrhea with ORS and zinc
• Prompt treatment of pneumonia and other illnesses
I
children, including for low-birth-weight infants; • Growth monitoring and periodic checks
b. Weight gain of the infant should be monitored weekly Adolescent girls: Future mothers
to observe changes; • Optimum nutrition
c. If the infant does not gain weight, or loses weight while • Education in parenting and mothercraft
the mother or caregiver is receiving support for • Marriage after 18 years of age
breastfeeding, then he or she should be referred to Society Level Action
inpatient care; • Safe water and sanitation
d. Assessment of the physical and mental health status of • A culture of good nutrition
mothers or caregivers should be promoted and relevant • Maternity and child care leave to enable women to breastfeed
treatment or support provided. and to take care of infants and children
• Creches for children of working women
Preventing Undernutrition • Promoting breastfeeding at workplace
Since childhood undernutrition is multifactorial, it can • Cash support to pregnant and lactating women (as being
only be prevented through interventions acro~s sectors. provided by the government)
Action is required at the individual and societal level • Socio-economic development, high income, equity
(Panel 2). Health and wellbeing of girls, women and • Education of women and men
children must be ensured. Underlying social determinants • Women's empowerment
such poverty, illiteracy, discrimination and social • Food security at the household level
insecurity must be addressed. Convergence of health • Nutrition promoting agriculture
programs (antenatal care, facility birth, ho~e based
newborn care, immunization, IMNCI, etc.) with I~~S provided at a center called the 'Anganwadi'. A package
initiatives (feeding counseling, supplementary nutrition of six services is provided under the ICDS Scheme:
and preschool education) must converge. a. Supplementary nutrition for mother and the child. The
norms are given in Table 7.14.
Integrated Chfld Development Services (/CDS) b. Immunization of pregnant women and infants ·a s per
The ICDS program seeks to directly reach out to children, the national program.
below six years, especially from vulnerable ~oups and c. Nonformal preschool education. Stimulating learning.
rem t The Scheme provides an integr ated d. Health check-up. This includes health care of children
o e areas. · h h
approach for converging basic services t . roug less than six years of age, antenatal care of expectant
community-based workers and helpers. The services are mothers and postnatal care of nursing mothers. These
- 1oa I Essential Pediatrics
services are provided by the ANM and medical officers Suggested Reading
under the RCH programme. The various health services • • Bhandari N, Mohan SB, Bose A, et al. Efficacy of three feeding
include regular health check-ups, immunization, regimens for home-based management of chi~dren _wi~h
uncomplicated severe acute malnutrition: a randonuzed trial m
management of malnutrition, treatment of diarrhea, India. BMJ Global Health 2016;l :e000144. doi:lO.l 136/bmjgh-2016-
deworming and distribution of simple medicines. 000144.
e. Referral services. During health check-ups and growth • Dalwai S, Choudhury P, Bavdekar SB, Dalal R, et al. Ind~an
monitoring, sick or malnourished children are referred Academy of Pediatrics. Consensus statement of the Indian
to the primary health center or its subcenter. Academy of Pediatrics on integrated management of severe acute
malnutrition. Indian Pediatr 2013;50:399-404.
f. Nutrition and health education. Healthy behaviors and
• National Family Health Survey 4. http:/ /rchiips.org/NFHS/pdf/
detection and treatment of sickness.
NFHS4/India.pdf
Under the POSHAN Abhiyaan, a flagship mission of • WHO Child Growth Standards and the identification of severe
the Prime Minister launched in February 2018, a new acute malnutrition in infants and children. A joint statement by
impetus has been given to nutrition program. The goals WHO and UNICEF. 2009. Accessed from http//who.int/nutrition/
for this three-year mission are to: publications/severemalnutrition/ 9789241598163-eng.pdf
• Reduce stunting in children (0-6 years) @2% per annum • WHO. Guideline updates on the management of severe acute
malnutrition in infants and children, 2013.
• Reduce under-nutrition (underweight prevalence) in • World Health Organization. Technical note Supplementary foods
children (0-6 years)@ 2% per annum for the management of moderate acute malnutrition in infants and
• Reduce low birth weight (LBW) @ 2% per annum children 6-59 months of age. 2012
• Reduce prevalence of anemia amongst young children • World Health Organization. The management of nutrition in major
(6-59 months) @ 3% per annum emergencies. Geneva: World Health Organization; 2000
Chapter
8
Micronutrients in
Health and Disease
Rajni Sharma • Arvind Ba~a.
Vitamins are organic compounds, required in small Intakes of micronutrients recommended by the National
amounts, for maintenance of health and normal growth that Academy of Science 2006 are available at www.nap.edu.
are not synthesized in the body and must be obtained from Intakes proposed by the Indian Council of Medical
the diet. They can be categorized into fat-soluble (A, D, E, Research in 2010 are listed in Table 6.1 and are also
K) and water-soluble forms (B complex vitamins, C and available at icmr.nic.in/final RDA-2010.pdf
folate). The former control protein synthesis at either
transcriptional or post-transcriptional level and perform FAT-SOLUBLE VITAMINS
diverse biochemical functions, as hormones (e.g. vitamin
D), antioxidants (e.g. vitamin E) and regulators of tissue Vitamin A
growth and differentiation (e.g. vitamin A). Several Vitamin A (retinal) is derived from natural plant pigments
vitamins (e.g. B complex vitamins) function as precursors called carotenoids (provitamin A) that are converted to
for enzyme cofactor biomolecules (coenzymes) that act as retinal in the body and stored as retinal palmitate in the
catalysts and substrates in metabolism. Breast milk is liver. Retinal is further converted to the active forms of
deficient in vitamins D and K and exclusively breastfed vitamin A: Retinal and retinoic acid.
infants must be supplemented with these vitamins (Box 8.1). Being a fat-soluble vitamin, vitamin A is absorbed as a
Certain minerals are essential to support biochemical part of chylomicrons.
processes involved in cell structure and function.
Important minerals include calcium, chloride, cobalt, Physiological Functions
copper, iodine, iron, magnesium, mang~ese, m~lybdenum, Retinal is converted to retinal which plays an important
nickel, phosphorus, potassium, seleruum, sodmm, sulfur role in vision especially night vision. Within the eye, 11-
and zinc. The amount required varies from >100 mg/day cis-retinal, an isomer of retinal, is bound to rhodopsin (rod
(major minerals including sodium, potassium, chloride, cells) and iodopsin (cones). As light enters the eye, 11-cis-
calcium, magnesium and phosphorus) t~ <100 mg/ day retinal is isomerized to the all-trans form. The all-trans-
(trace minerals including iron, copper, zinc). Ultra-trace retinal dissociates from the opsin in a series of steps called
minerals are required in miniscule amounts (<1 mg/ day). bleaching. This isomerization induces a nervous signal
Marginal or severe imbalances in t~~ce elemei:t~ ar~ nsk along the optic nerve to the visual center of the brain.
factors for several diseases. In addition to defic1enc1es of Subsequently, the all-trans-retinal is recycled and
iron and iodine, features of deficiency of copper, zinc and converted to 11-cis-retinal form via a series of enzymatic
selenium are recognized. reactions. Deficiency in vitamin A inhibits the reformation
of rhodopsin and leads to night blindness. Retinal and its
Box 8. 1: Breast milk and vitamins derivative retinoic acid bind to intracellular receptor,
Breast milk is the complete food .for infants. However, breas_t regulate gene expression and induce the synthesis of
1milk is deficient in vitamins D and K. · ·
proteins involved in growth and cell differentiation.
Breast milk contains only 30-40 IU/L of vitamin D, whereas Retinal is also required for production of glycoproteins
l the RDA is higher. Exclusively breastfed babies require vitamin and mucus and helps to maintain the integrity of epithelial
D supplementatio~ _in the dose of 400 IU I day to preven\ tissues. Vitamin A deficiency leads to drying of epithelial
rickets. , . ; ' - ·· · · ~ surfaces and excessive keratin formation of the surface.
Vitamin K is produced by. ~e gut ~croflora. It ma! take ·
sometime for a newborn ~t to be colonized by b~cter~a ~d Sources
: start producing the vitamin. All babies should receive v1tamm , Carotenoids (provitamin A) are found in green and yellow
. K at b.i rth t~ preve~~~d~.gic di~~~e ~_:w~~m:_-_. ,, plants including carrots, dark-green leafy vegetables,
109
-110 Essential Pediatrics
Vitamin A Deficiency
Mild vitamin A deficiency manifests with follicular fig. 8.1: Bitot spot showing foamy frothy sharpl~ der:narcat~
hyperkeratosis of the skin that consists of rough skin with whitish spot on the temporal side of bulbar coniunct1va. Thi~ 1s
raised hyperkeratotic patches resembling goosebumps. formed by keratinization of the epithelium and ac~umulati~n
Defective dark adaptation is a characteristic early clinical of mucus, bacteria and debris on the surface. and is a classic
feature, resulting in night blindness. The ocular epithelium sign of vitamin A deficiency [Courtesy: Dr Vanathl, RP Centre,
becomes dry (xerophthalmia) (Table 8 .1) and hyper- AllMS)
keratinized with the appearance of small foam-like silvery
lesions on the conjunctiva (Bitot spots) (Fig. 8.1). More
severe deficiency leads to hyperkeratinization of the
cornea with the appearance of corneal opacity, which can
progress to ulceration and infection (keratomalacia)
(Fig. 8.2). Loss of mucosal integrity of the respiratory,
gastrointestinal tracts and impaired immunity predispose
children to severe systemic infections especially measles.
In developing countries, vitamin A deficiency is the
leading cause of blindness in preschool children.
Malnourished children and those with fat malabsorption
(celiac disease and liver disease) are predisposed to
vitamin A deficiency.
Laboratory tests show mild leukopenia and serum
retinol level of 15 µg/ dL or less (normal 20 to 80 µg/ dL).
Treatment of vitamin A deficiency: Specific treatment • _J
consists of oral vitamin A at a dose of 50,000 IU, 100,000 Fig. 8.2: Bilateral keratomalacia in a child with protein energy
IU and 200,000 IU in children aged <6 months, 6-12 malnut~ition and severe vitamin A deficiency precipitated by
months and >1 year, respectively. The same dose is an episode of pneumonia . Note the bilateral corneal
repeated next day and 4 weeks later. Alternatively, opacification and corneal perforation in the left eye.
parenteral water-soluble preparations are administered
in children with persistent vomiting or severe is an emergency and requires parenteral administration
malabsorption (parenteral dose is half the oral dose for of 50,000 to _100,000 IU (15 to 30 mg retinol). In case of
children above 6-12 months and 75% in <6 months old). keratomalacia, local treatment with antibiotic drops and
Clouding of the cornea in a child with vitamin A deficiency ointment and padding of the eye enhances healing.
Preve11tio11: Under the National Vitamin A Prophylaxis
. Table a.·;; WHO classificati~I'! of xer~phthalmi~ ". ·:: ~l Prog_ramme, spons~red by the Ministry of Health and
Primary signs Secondary signs Family children between 1 and 5 years were ··
. Welfare,
.
X1A Conjunctiva! xerosis XN Night blindness previously given ora1~oses of 200,000 JU vitamin A every
X1 B Bitot's spots XF Fundal changes six
. months. Evaluation . studies si·nce th en reveaIed ·
X2 Corneal xerosis XS Corneal scarring inadequate covera~e m most states. Current! , vitamin A
is given only to chi~dren less than three ye!rs old since
X3A Corneal ulceration (<1/3 of cornea) they are at greatest nsk and the administr ti' f th .c..,.t
X3B Corneal ulceration (>1/3 of cornea) . linked w1'th routine
two doses is . irnm,,.,.;_ ati ono . e1u" ve
..... U.£.a on to unpro
Mlcronutrlents In Health and Disease 1111 -
the coverage. Hence, a dose of 100,000 IU is given with chylomicrons and transported to the liver. Being a fat-
measles vaccine at 9 months and 200,000 IU with the DPT soluble vitamin, vitamin D absorption is decreased in
booster at 15-18 months. In endemic areas, 3 more doses conditions of fat malabsorption such as chronic
are administered at 24, 30 and 36 months. Dietary pancreatitis, cystic fibrosis, etc.
improvement is necessary to prevent vitamin A deficiency. In the liver, the enzyme 25a.-hydroxylase hydroxylates
Children with measles and severe malnutrition should vitamin 0 2 and 0 3 to form 25-hydroxyvitamin 0 2 [250HD2
receive vitamin A at 100,000 IU, if <1-year-old and 200,000 or ergocalcidiol] and 25-hydroxyvitamin D3 [250HD3 or
IU, if older. cholecalcidiol], respectively. This biochemical step is
substrate dependent and occurs without any negative
c arotenemla feedback control. 250HD (predominantly in the form of
Beta-carotene is an important precursor of vitamin A in cholecalcidiol) is then released into the bloodstream and
vegetable-based diets; 10 µg ~-carotene has the biological has a biological half-life of approximately 3 weeks. Due
potency of I µg retinol. Excessive dietary intake of carotene to its long half-life, serum cholecalcidiol level is considered
containing foods, most commonly carrots and carrot- the biochemical marker for vitamin D status in the body.
containing products, can lead to deposition of carotenoids Cholecalcidiol (250HD3) undergoes further hydroxyla-
in keratin and subcutaneous fat. At high plasma levels, tion in the kidneys by the enzyme l cx-hydroxylase to form
ye~low pigmentation (carotenemia) shows in superficial 1,25-dihydroxyvitamin 0 3 [l,25(0H)iD3] or cholecalcitriol.
skin (face, palms and soles), but not in sclerae. The color Cholecalcitriol is the active form of vitamin D and affects
returns to normal within 2-6 weeks of discontinuing calcium homeostasis through its action on the intestine,
intake of carrots. kidney and bones. In the intestine, it increases absorption
of calcium by inducing the formation of calcium transport
Hypervltamlnosls A and Teratogenlclty proteins and intracellular calcium-binding protein
Vitamin A toxicity occurs ingesting more than 50,000 iu; (calbindin) in the enterocytes. In the kidney, cholecalcitriol
day of vitamin A for several months in the form of fish enhances calcium resorption in the renal tubules by a similar
liver oil, therapeutic vitamin preparations or, in mechanism. It decreases the activity of renal 1-cx-
adolescents, as retinal or retinoic acid for acne. Acute hydroxylase enzyme via feedback inhibition, and stimulates
manifestations include pseudotumor cerebri (vomiting, renal 24-hydroxylase enzyme activity (that inactivates both
irritability, b~lging fontanel, diplopia, headache). Patients calcidiol and calcitriol). In the bone, calcitriol helps in
with chronic hypervitaminosis may have anorexia, dry stimulating osteoclast activity and proper mineralization
skin, alopecia, painful joints and hepatosplenomegaly. of bone. Thus, the overall effect of cholecalcitriol in the body
Vitamin A is teratogenic, if taken in high doses in early is to increase serum levels of calcium.
gestation. The WHO recommends that vitamin A in The activity of renal lcx-hydroxylase enzyme is affected
take during pregnancy should not exceed 3000 µg daily by other factors as well: Both parathyroid hormone and
or 7500 µg every week. low serum phosphate levels increase the activity of 1-cx-
hydroxylase, whereas the hormone fibroblast growth
factor-23 (FGF-23), produced by bone, decreases its activity
Vitamin D
(Fig. 8.3).
Vitamin D, the 'sunshine vitamin', is produced in the
upper layers of the skin on exposure to solar ultraviolet B Sources
(UVB) radiation. Under normal conditions, endogenous The dietary sources of vitamin D include fish and fish oils,
synthesis of vitamin D is sufficient to meet the body's egg yolk and some plants. However, natural diet contains
needs. However, when endogenous production is low, very little vitamin D and adequate endogenous production
due to a variety of factors, diet becomes an important or dietary supplementation is essential to prevent
source of the vitamin. deficiency.
Adequate vitamin D synthesis in the skin depends on
Metabolism and Mechanism of Action various factors including time spent outdoors and the
There are two forms of vitamin D: Vitamin D 2 amount of clothing. The dermal pigment melanin
(ergocalciferol, made in plants) and D3 (cholecalciferol, decreases the amount of UVB rays that reach the epidermal
made in animals). Vitamin D 3 is synthesized from layers containing the substrate, 7-dehydrocholesterol.
7-dehydrocholesterol in the dermis after exposure to UVB Hence, individuals with dark skin require more duration
solar irradiation of wavelength 290-315 nm. It is then of sun exposure to make the same amount of vitamin D.
bound to vitamin D-binding protein and transported to Moreover, the amount of UVB radiation reaching the skin
the liver. Vitamin D can also be derived from the diet from depends on the time of the day, latitude, season, cloud
either plant (vitamin 0 2) or animal (vitamin D3) sources. cover and presence of air pollutants. Excessive exposure
Dietary vitamin Dis readily absorbed from the duodenum to sunlight does not increase vitamin D production as
by an active transport system and incorporated into previtamin 0 3 is degraded into inert products such as
-112 Essential Pediatrics
~ VT~:~
··-
"
"
.
...,,
•..:.'
i:·
24,25-dihydroxyvltamin D 24·hydroxylase
(inactive) 25-hydroxyvitamin D
Kidney
1 ia-hydroxylase Parathormone
-I
·!1 •: .-------
+ Low phosphorus
Fibroblast growth factor
Fig. 8.3: Vitamin D metabolism. Serum levels of fibroblast growth factor-23 are elevated in response to increased serum phosphate
and also inhibit the production of parathormone . .'
lumisterol-3 and tachysterol-3, and vitamin D 3 photo- Patlwphysiology: Vitamin D deficiency leads to ·
isomerizes to suprasterol and inert products. hypocalcemia which stimulates the parathyroid gland to .
secrete parathorrnone (PTH) . Increased PTH levels
Vitamin D Requirements stimulate osteoclastic activity of bone and help restore the ·
The daily requirement of vitamin Dis 10 µg (400 IU) per blood calcium levels to normal. However, PTH leads a·
day in infants and 15 µg (600 IU) per day in children concomitant loss of phosphate from the kidney leading to
> 1 year age. When endogenous production is inadequate, low serum phosphate levels.
vitamin D needs to be supplied through dietary supplemen- Under normal conditions of growth, the cartilaginous
tation. gro~t~ pl.a te undergoes mineralization by enchondral
The risk factors that predispose to vitamin D deficiency calcif1cat10n. In this process, the chondrocytes
include limited exposure to sunlight, full body clothing, h)'.'pertr~p~y and then undergo apoptosis followed by .
dark skin, debilitation, living at high latitudes, disability rruneralization. Adequate amount of phosphate is essential
and predominant indoor living. for the apoptosis of the chondrocytes. In the absence of
Breast milk is a poor source of vitamin D containing adequate phosphate, the chondrocytes continue to
only 3o-40 IU per liter and exclusively breastfed infants hypertrophy and this leads to the characteristic swellings :
are at high risk of developing vitamin D deficiency and at the growth plates. Mineralization of the bone is also --
rickets unless supplemented. Therefore, exclusively decr~ased leading to osteomalacia and bendin of weight :.
breastfed babies should receive 400 IU of supplemental bearing bones. g .
vitamin D per day. Formula milk has 400 IU of vitamin D . Osteomalacia is a term used for d ecreased nuner . aliza·•
per litre and children getting less than 1 litre formula .per hon of the bony ~atrix and is seen both in children and .
day also require supplementation. Pregnant and lacta~g adults, whereas rickets is a disease f
. . d'f
. b nes.
o growmg o
mothers should receive 600 IV of vitamin D per day m 0 s t eoma1acia . th e 1atter
is . i ferent from 0 s t eoporos1s;
order to meet their daily requirements. refers.to a( proportionate
. loss ofb one vo1urne, both orgalll·c i
matrix osteo1d) and mineral, w h'ic h occurs mo st ~
Rickets commanly d ue to prolonged intake o f corticostero1
. 'ds. .. '
Rickets is a disease of growing bone. It is derived from Nutritional Rickets
the word 'wrickets' meaning 'twisted' referring to the .. !.:
characteristic bony deformities or 'bow le~s· of rick~t~. The Vitamin D deficiency is the leadin c . oth ':·
in developing and d g ause of rickets, b
most common cause of rickets is a nutritional def1c1ency eve 1oped t . Th gh
of vitamin D and less commonly, a dietary deficiency of nutritional rickets had once b .coun nes. ou . ,
(' . een vrrtually eradicated Ul ·
calcium or phosphorus. developed nations by fortificat ion' . or d'irect .
of milk
Mlcronutrlents In Health and Disease I 11a 11
~d~strati?n o~ vitamin D, recent reports suggest that is an increased risk of fracture even with minimal trauma.
it is beco.mmg increasingly common in exclusively Pelvic deformities can develop including outlet narrowing
breastfed infants particularly those who not get vitamin which can be troublesome for females at a later age by
~uppl.e~ents. Apart from poor dietary intake and increasing the risk of obstructed labor.
insufficient exposure to sunlight, vitamin D deficiency
Evaluatiou: The initial evaluation of rickets includes
may ~es1:11t fro.m various malabsorption syndromes, serum biochemistry and radiographs of the wrists and/
chr~ruc liver disease and use of anticonvulsant drugs.
or knee joints. Serum levels of calcium may be normal or
·".11hco~~uls.ant drugs and antitubercular drugs (isoniazid, low, serum phosphate will be low and alkaline phosphatase
n famp1cin) induce hepatic cytochrome P450 oxidase that
high. Radiologic changes are characteristically seen at the
leads to conversion of 250HD3 into its inactive metabolites.
metaphysis. The first change is loss of normal zone of
As mentioned, n1:1tritional rickets may also occur provisional calcification adjacent to the metaphysis seen
seconda~ to se~ere dietary deficiency of calcium that can as a blurring or a frayed appearance of the metaphyseal
o::.cur with o~ ":'1thout concomitant vitamin D deficiency. margin (fraying). Cartilage hypertrophy leads to widening
Dietary deficiency of phosphate is rare due to the of the growth plate giving the appearance of cupping and
widesp_read availability of phosphate in the diet but may widening of rnetaphyseal ends (splaying) (Fig. 8.5).
0ccur m preterm babies who have high phosphate Weight-bearing and stress on uncalcified bone gives rise
requirements for growth. to bowing of limbs. Eventually, a generalized reduction
Clinical features: The classical features of rickets include in bone density is seen (osteopenia).
swellings of the wrist and ankles and leg deformities in The diagnosis of vitamin D deficiency is based on low
the form of bow-legs (genu varum) or knock-knees (genu circulating levels of 250HD3 . Values above 20 ng/mL are
valgurn) (Fig. 8.4). From head to toe, the following signs considered normal, between 10 and 20 ng/mL are
may be seen: Frontal bossing, delayed closure of anterior insufficient and below 10 ng/mL are indicative of
deficiency (Table 8.2).
fontanelle, craniotabes (soft skull bones), delayed dentition
and beaded appearance of the anterior costochondral
junctions (rachitic rosary). A depression (termed Harrison
Ma1iagement: Treatment of nutritional rickets requires
administration of high doses of vitamin D. Previously, oral
n·
sulcus) may be evident along the lower border of the chest bolus doses of vitamin D (also called Stoss therapy) were
at the site of insertion of the diaphragm which appears preferred which consisted of 60,000 IU of vitamin D daily
due to the pull of the diaphragm on the weakened chest or on alternate days to reach a maximum total dose of
wall. Apart from this, other features of rickets include 6,00,000 IU. There is now consensus to use lower daily
hypocalcemic seizures, muscle weakness, hypotonia, doses of 2000 IU, 3000-6000 IU, and 6000 IU for infants
failure to thrive and irritability (due to bony pains). There below 12 months, 1-12 years and more than 12 years,
-
Fig. 8.5: Radlograph of wrist In 4-year-o ld boy with rickets. Note
Fig. 8.4: A 5-year-old child with rickets with mild frontal bossing, widening, cupping and fraying at the metaphyseal ends of
Wide Wrists and bow legs forearm bones
-114 Essentlal Pediatrics
[~ry rickets
Table 8.2: Vitamin D levels In serum
25-hydroxyvitamin D level (nglmL) ~h~hate]
Deficient Less than 10
~[
Insufficient 10-20 r High
Optimal 20-60 Low or normal
[eio!d ~
High 60-90 Chronic kidney disease
.
Toxic Greater than 90
____ __
[
r Normal
respectively, for a duration of 12 weeks, followed by a Low
_, ___ t _ ___,
maintenance dose of 400-600 IU /day (Table 8.3). Higher
dos.es can ~e given as oral bolus dose (Stoss therapy) in Renal tubular acidosis
serum PTH, calcium I
patients with suspected noncompliance to daily therapy.
~ral calcium su~plements (30-75 mg/ kg/ day) should be
High PTH, low or normal calcium Normal PTH, normal calcium
given to all patients for 2 months. Following adequate
therapy, most patients with vitamin D deficiency rickets
show radiological evidence of healing (Fig. 8.6) within Vitamin o dependent rickets Hypophosphatemic ricketsj
4 weeks. Reduction in blood levels of alkaline phosphatase
and resolution of clinical signs occur slowly. The X-ray Fig. 8. 7: Biochemical evaluation of a child with refractory rfctets
and blood biochemistry should be rechecked after
completion of therapy. If radiologic healing cannot be Hypervltamlnosls D
demonstrated, despite adequate therapy, patients should Excessive vitamin D due to over-dosage can result in
be evaluated for refractory rickets (Fig. 8.7). hypervitaminosis D (ser um levels> 100 ng/ mL). This can
Refractory Rickets
Rickets that does not respond to the usual treatment of
~utrition~l ricke.ts is called refractory rickets. The diagnosis
is made m patients with no radiological healing after
vitamin. D therapy. It can be broadly classified into two
categories: J?efects in vitamin D metabolism and low
phosphate disorders. Figure 8.7 outlines the approach to
a case of refractory rickets.
\IDDR type I: This condition is chara~teri~ed by a enzyme is responsible for the breakdown of FGF-23 and
deficiency of the enzyme, 25-hydroxyvitamm D la.- enzyme deficiency leads lo high FGF-23 levels and
hydroxylase. Reduced blood levels of calcium, normal to excessive renal loss of phosphate. FGF-23 also decreases
Jow phosphate and elevated alkaline phosphatase are the activity of renal la-hydroxy lase. Therefore, the blo~d
characteristics. Blood levels of 25(0H)D3 are normal but levels of 1,25(0H)iD3 are low despite hypoph~s~hatem1a
those of 1,25(0H}i03 are markedly decreased despite (which normally activates la-hydroxylase activity).
hypocalcemia. Clinical features: Lower limb deformities, such as coxa
The clinical features are similar to vitamin D deficiency vara, genu valgum, genu varum and short statu~~' are
rickets and include hypotonia, growth failure, motor common in hypophosphatemic rickets. A~normaht1es_of
retardation (poor head control, delayed standing and maxillofacial region and premature fus10n of cranial
walking), convulsions due to hypocalcemia, anemia and
occasionally respiratory difficulty. Physical examination
sutures may lead to deformities o! skul~. Dental
abnormalities are commonly seen including pulp
shows thickening of wrists and ankles, frontal bossing, deformities with intraglobular dentin, and frequent dental
widely open anterior fontanelle, rickety rosary, bony abscesses. Symptoms of hypocalcemia including teta~y
deformities and positive Trousseau and Chvostek signs. and muscle weakness, which are generally seen m
Dentition is delayed and development of tooth enamel disorders of vitamin D metabolism, are absent in
impaired. hypophosphatemic forms. The mother of affected
The treatment of VDDR type I consists of physiological patient(s) may have bowing of legs and short stature or
doses of alpha-calcidiol or calcitriol (0.25 µg daily). Most fasting hypophosphatemia.
subjects require concomitant treatment with calcium with
or without phosphate supplements. With appropriate Evaluation: The level of serum calcium is normal or
therapy, the serum calcium levels rise and radiological slightly low (9-9.5 mg/dL), that of phosphate d~cre~sed
healing occurs within 6 to 8 weeks. (1 .5-3 mg/ dL). Serum alkaline phosphatase level 1s raised.
PTH levels are normal. Blood levels of 1,25(0H)i03 are
\!DDR type II: The features are similar to VDDR type I. inappropriately low for the level of serum phosphate.
There is end organ resistance to 1,25(0H)z03. This leads Urinary phosphate excretion is increased with decreased
to virtual abolition of actions of l,25(0H)zD3 , despite its tubular reabsorption of phosphate.
markedly raised levels in circulation (secondary to
Management: Oral phosphate and vitamin D supplements
hypocalcemia and low 24-hydroxylase activity).
are the mainstay of therapy. Phosphates are provided at a
Early onset of rickets, a high prevalence of alopecia and dosage of 30-50 mg/kg (total 1-3 g elemental phosphorus)
ectodermal defects (oligodontia, milia and epidermal
divided into 5 to 6 equal parts and can be given in the
cysts) are characteristic. Hypocalcemia, secondary form of }oulie solution or as neutral phosphate effervescent
hyperparathyroidism, elevated circulating levels of l,
tablets. Joulie's solution contains 30.4 mg of phosphate/
25(0H)i03 and an absence or decreased response to mL. Diarrhea is a frequent problem with higher doses.
vitamin D analogs are seen. The response to treatment in
patients with VDDR type II is not satisfactory. An Vitamin D supplementation is necessary for the healing
occasional patient may get clinical and biochemical of rickets. Treatment is started with alpha-calcidiol at a
dose of 25-50 ng/ kg/ day (maximum 2 µg / day) until there
improvement and radiological healing following long-
is biochemical and radiological evidence of healing of
term administration of large amounts of intravenous or
oral calcium. rickets. Periodic monitoring of serum and urine levels of
calcium and phosphate is essential. A level of serum
phosphate greater than 3.0 to 3.2 mg/ dL is desirable.
Faml/ia/ Hypophosphatemic Rickets
Normal level of serum phosphate is essential for Other Causes of Rickets
mineralization of the growth cartilage. Some inherited Chronic kidney disease: Patients with chronic kidney
clinical disorders lead to excessive loss of phosphate in disease have low 1,25(0H)z03 levels due to poor
the urine with very low serum phosphate levels and can la.-hydroxylase activity in the kidney. Rickets may
present as refractory rickets. The most common inheritance occasionally be the presenting manifestation of patients
pattern of these familial hypophosphatemic disorders is with tubulointerstitial disease. Serum levels of calcium
an X-linked dominant form with variable penetrance. are low and those of urea, creatinine, and PTH are
Rarely, an autosomal recessive inheritance or sporadic increased. In contrast to other causes of v itamin D
forms can also occur. deficiency, serum phosphate levels are high. Therapy
~atlwgenesis: The gene for X-linked hypophosphatemic consists of restricting phosphate intake and providing
rickets is termed the PHEX gene (phosphate regulating supplements of calcium and active vitamin D analogs.
gene with homology to an endopeptidases on the X Renal tubular acidosis: Proximal or distal renal tubular
chromosome) which produces an endopeptidase. This acidosis (RTA) are important causes of refractory rickets
-
111 ns ~~~~--------~~~~--.!E~s!se~n~t~la~l~P!e~dl~a~tr~lc~s------------------~~~---~-
in children. The conditions are characterized by Vitamin E Deficiency s muscle weakness, peripheral
hyperchloremic (normal anion gap) metabolic acidosis f .. ncycause I f t .
with normal blood levels of urea and creatinine. Patients Vitamin Ede 1cie 1Yt'c
1 'anemia. n an• s particularly .
c
n europathy, an d hemo
with proximal RTA have a generalized urinary loss of born m". ... state of relative tocopherot
bicarbonate, phosphate, glucose and amino acids from the P reterm babies are 'b t d to limited placental transfer
'fJ1 ·sis attn u e f" . . .
proximal tubules. The use of bicarbonate and phosphate deficiency. 1 • dietary de 1ciency, intestinal
.
of vitamin · E' relativeid rowth. The ns · k o f vi"tarnm· ·E
supplementation (in proximal RTA) results in healing of
rickets. malabsorption and .ra~ f'"'gnts fed on formulae high in
· h ' hmm"
deficiency is ig d low tocopherol content. As the
011coge11ous rickets: Benign mesenchymal tumors may polyunsaturated fats ant res tocopherol absorption
secrete fibroblast growth factor-23 (FGF-23) that results . . stem ma u ' . A -
digestive sy . bl 0 od levels nse. comrnon
in phosphaturia, hypophosphatemia and refractory 1
improves and ts babi'es is with hemolytic anemia
rickets. Removal of the tumor reverses the biochemical · · preterm ' ·
presentation m 0 lob in range between 7 and 9 g/ dl.
abnormalities and heals the rickets. Th~ levels of .hemd ~ erbilirubinemia are accompanied
Metapl1yseal dysplasia: It is a type of skeletal dysplasia
Rehculocytosis an .YP . E Administration of iron
l 1 of v1tamm ·
with bony deformities and radiological findings that by 1ow eve s 1 sis unless vitamin E is also
mimic rickets. Short stature with bowing of legs and exac.e~ba tedsP
admmistere . aren e
11emot ~al therapy with vitamin E corrects
waddling gait are prominent. The classic biochemical
findings are characteristically absent. Hypercalcemia has hemolysis. . hf Ib ti
Old erehi'ld ren and adolescents wit at ma ad sorp on,
occasionally been reported in Jansen metaphyseal cho1estahc . 11ver
. di"sease or short bowel. syn rome . are .
chondrodysplasia. 't . E deficiency. Abetahpoprotemem1a,
prone to v1 amm . . . -
Fluorosis: Endemic fluorosis might present with bony caused by the genetic absence o! apohpoprotem B, IS
phosphatase and PTH are raised. Levels of fluoride are loss of deep tendon reflexes, loss of vibration and p~sition
increased in the community drinking water source. sense, ophthalmoplegia, muscle weakness, ptosis and
dysarthria.
Vitamin E Most malabsorption syndromes respond to large doses
Vitamin E belongs to a group of compounds called of oral vitamin E (15-20 mg/kg/ day) with amelioration ,·
tocopherols that are naturally occurring membrane of deficiency and improvement in neurological symptoms:
antioxidants. Tocopherols prevent polyunsaturated fatty Hypervltamlnosls E
acids (PUFAs) from getting oxidized by o_xygen-free
radicals. The absorption of vitamin E in.the gut .is enh~~ed Relatively large amounts of vitamin E, in range of 400 to
by simultaneous dig~stion ~d abs?rption of dieta1?' ~i~ids 800 mg tocopherol, have been taken daily by adults for
and medium chain tnglycendes. Bile and pancreatic JUICes months to years without causing any apparent harm.
enhance absorption of vitamin E, which i~ incorporated Occasionally, muscle weakness, fatigue, nausea and
into chylomicrons and delivered ~o t~e liver..From the diarrhea are reported in persons ingesting 800-3200 mg/
liver it is secreted with low density hpoprotems (LDL) day. Vitamin E intoxication, at dosages exceeding 1,000
and delivered to peripheral tissues. Red blood cell~, whi~h mg/ day, results in antagonism to vitamin K action and
contain about 20% of vitamin E in plasma m their risk of bleeding.
membranes, also participate in transport. Vitamin K
Nutritional requirements: Vitamin E requireme~t of Vitamin K e~sts in 2 forms: Vitamin K (phylloquinone)
normal infants is approximately 0.4 µg/kg bo~y we1?ht/ 1
that present m plants and vitamin K (menaquinone) that
day. For premature infants, 15 to 20 µg/ day is reqmred. is synthesized by intestinal bacteri/
The RDA for infants increases from 3 to 6 mg tocopherol
from birth to 2 years of age. One mg of tocopherol provides Ab.sorptio11 and meta~olism: The absorption of phyll<;
1.5 IU activity of vitamin E. ~~mone. and me~aq~mone requires bile and pancreatic
Sources: The common sources of vitamin E are. vegetable
~u1ce. Dietary. vitamm K is absorbed in the jejunum,_ ·
i~corp~rate~ mto chylomicrons and delivered to the
oils (com, cottonseed, safflower) and margarme. Other
sources include leafy vegetables, nuts, milk and eggs;
cir~ulation VIa ~he lymph. The liver is the primary site of ,
0
breast milk and colostrum are also rich sources. · actiolnl soofo°':1bta1?111.K. The total body pool of vitamin K .is -;•
sma , 10 emg m the liver. ~ "
Mlcronutrlents in Health and Disease I 111 111
Physiological function: The main role of vitamin K is as a Thiamine (Vitamin 81)
cofactor in post-translational carboxylation of glutamic Biologic action: Thiamine is essential for glucose
acid to form y-carboxyglutamates in the liver. Factors II metabolism and cellular energy generation. Thiamine
(prothrombin), VII, IX and X are vitamin K-dependent pyrophosphate, the active form of thiamine, is an
coagulation factors. The function of these proteins is to important cofactor in the citric acid cycle that is active in
facilitate the chelation of calcium ions to glutamate and the heart and brain. The vitamin is also involved in nucleic
platelet phosphatide, which is essential for the coagulation acid and fatty acid synthesis.
cascade to operate.
Nutritional requirements: Vitamin K requirements are met Requirements: Recommended daily allowance is 0.4 mg/
by combination of dietary intake and microbiological 1000 Cal of carbohydrate intake.
biosynthesis in the intestines. Vitamin K requirement of
newborns is 3 to 5 µg/ day, that increases to 10 µg/ day at DietanJ sources: These include human milk, cow milk,
2 years and 10 to 30 µg/day in older children. unpolished grains, eggs, organ meats (liver, kidney)
and legumes. Thiamine is sensitive to heat, sulfites,
Newborn babies, especially preterm babies, are
particularly prone to vitamin,K deficiency due to a pasteurization and sterilization.
combination of factors; vitamin K does not cross the
Deficiency: Thiamine deficiency results in beriberi that
placenta and they do not have adequate intestinal bacterial
affects people who consume diets based on polished rice,
flora to synthesize it endogenously. Moreover, breast milk
is a poor source of vitamin K containing only 2 µg/L when the intake is below 1 mg/ day. Three forms of
beriberi are described: Dry, wet and infantile. Dry beriberi
phylloquinone. Hence, newborns need to be supplemented
manifests as a peripheral neuritis with irritability,
with vitamin K to prevent manifestations of deficiency
including hemorrhage. paralysis of lower limbs, loss of deep tendon jerks, muscle
Riboflavin (Vitamin 82) "J?eficiency: Riboflavin deficiency occurs from inadequate . "
Riboflavin is a constituent of two coenzymes involved in intake or malabsorption. It takes 1-2 months to develop '
oxidation-reduction reactions of cellular respiration: and is associated with other deficiencies. . ,.
Flavin adenine dinucleotide (FAD) and flavin Features incl~~e photophobia, glossitis, cheilosis; · · ·
mononucleotide (FMN). A number of redox enzymes, angular stomahh~, seborrheic dermatitis (especially
including glutathione reductase and xanthine oxidase, around the nasolabial folds) and corneal vascularization.'
require flavin coenzymes.
D~agnosis_ of deficiency: Diagnosis should be considered
Riboflavin requirements: The recommended daily intake with. a history of .dietary
is 0.4 mg/1000 Cal for infants and 0.8- 1.2 mg/1000 Cal . . . defi"ci· ency an d cl"m1c · al
marufestations. A reliable indicator of riboflavin status is ·
for children. the daily losses of the vitamin·, urm·a ry excretion
· of Iess -
•
0
Dietan1 sources: Meat, milk, eggs, cereals and vegetables than10
. . Yoofmtakeover24
. hoursis m· d'ica ve o efi.
ti" fd aency·· ..·.·
(broccoli, spinach and asparagus) are good so~rces. Activity of glutathione reductase ·n th · a · ·~
. . 1 ery rocytes gives .
Riboflavin is resistant to oxidation and to heat and is not functional mdex of flavin coenzyme act"ivity· · f t r
co ac o • ··
destroyed by pasteurization. Human milk contains 40- . increase of 20% above the b asa11eve1' m
induced · d ica
" tes
70 µg/100 Cal of riboflavin and cow milk 250 µ g /100 Cal. d eficiency.
Mlcronutrlents In Health and Disease
I 119 •
Treatment: Children are treated with 3-10 mg of oral Pyridoxine deficiency may cause peripheral neuro-
riboflavin daily for several weeks; infants respond to pathy, refractory seizures, dermatitis and microcytic
1 mg daily. Therapeutic doses of vitamin help in anemia. Pyridoxine is given 10-50 mg/day to patients on
improving corneal lesions rapidly. INH (isoniazid) to prevent peripheral neuropathy and
other neurologic effects. For refractory seizure, 100 mg of
Niacin (Vitamin 83)
pyridoxine is injected intramuscularly.
Nicotinic acid and nicotinamide, biologically equivalent
vitamins, are both referred to as niacin. This vitamin can Biotin
be synthesized in the body from tryptophan, however, Biotin deficiency has been observed in individuals who
the conversion ratio is 60:1, requiring large amounts of consume a large number of raw eggs (rich in avidin) for
tryptophan to meet niacin needs. several months. The avidin is not hydrolyzed by gastro-
intestinal enzymes; it binds biotin and prevents its
Sources: Milk, eggs, cereals and leafy vegetables are good
absorption. Cooking of eggs destroys avidin.
sources of typtophan. Deficiency occurs in areas where
Clinical features of biotin deficiency include anorexia,
maize is the staple food as the niacin in maize is present
vomiting, dry scaly dermatitis, glossitis and hyper-
in bound form and not easily absorbed. The vitamin is
cholesterolemia. Long-term parenteral alimentation
resistant to heating. Human milk contains 30 mg/100 cal
without biotin can also lead to deficiency in pediatric and
of niacin compared with 0.12 mg/100 cal in cow milk.
adult patients. Multiple carboxylase deficiency is a genetic
Niacin requirements: Requirements are expressed in terms disorder affecting the activity of carboxylase synthetase.
of niacin equivalents (NE). One NE equals 1 mg of niacin This condition responds to large doses of biotin. Another
or 60 mg of tryptophan. RDA for niacin is related to dietary genetic defect affects the activity of biotinidase, an enzyme
energy intake; the recommended intake is 6.4 to 8 NE/
1000 cal, human milk provides about 8 NE/1000 cal.
Niacin deficiency: Niacin deficiency leads to pellagra
which is characterized by three Ds: dermatitis, diarrhea
involved in the recycling of biotin.
Dietary sources of biotin include liver, egg yolk, milk,
yeast extracts and meat. Recommendations are 0.15 mg
biotin in the multivitamin supplements for infants and .
children. For treatment of biotin deficiency, oral
I
I
t
and dementia. The cutaneous lesions consist of a administration of 2-5 mg daily for 2 to 3 weeks is
symmetrical pigmented rash in body parts exposed to recommended for mild cases. A parenteral biotin dose of
sunlight especially the neck (Casal necklace). More acute 200 µg daily for 2 to 5 days is used in severe cases.
cases may progress to vesiculation, ulceration and
secondary infection. Neurologic symptoms include Pantothenic Acid
apathy, headache and loss of memory. In most chronic Pantothenic acid (vitamin 6 5) is present in virtually all
forms, posterolateral cord degeneration and peripheral naturally occurring foods and is also synthesized by micro-
nerve lesions are seen. organisms. Pantothenate is absorbed in the proximal small
Diagnosis of niacin deficiency: The diagnosis is suspected intestine; in the liver, it becomes a part of coenzyme A,
on history of inadequate diet, isoniazid treatment or which is essential for metabolism of fatty acid, proteins
chronic alcohol ingestion when typical manifestations are and carbohydrates. Isolated pantothenate deficiency is
present. Determination of urinary excretion of N 1 - rare and includes burning feet, insomnia and
methylnicotinamide is most helpful; normal 24 hours gastrointestinal symptoms. The suggested daily intake is
excretion is between 4 and 6 mg, values below 3 mg 2- 3 mg for infants and 3-5 mg for children.
indicate deficiency. In pellagra, these values are usually Cobalamln (Vitamin 812)
between 0.5 and 0.8 mg/ day.
Cobalamin or vitamin 6 12 consists of three compounds:
Treatment of pellagra: The daily dose for treatment is methylcobalamin, 5'-deoxyadenosyl cobalamin and
about 10 times the recommended dietary intake (50-300 cyanocobalamin. The first two are active forms of vitamin
mg/ day). Parenteral therapy is considered when B12 in the body while cyanocobalamin is most common
gastrointestinal absorption is deficient. Prevention of commercially available preparation.
pellagra is achieved by an adequate protein diet containing
tryptophan and niacin-rich foods. Sources: Vitamin 6 12 is produced by intestinal micro-
organisms in animals. Humans do not p~oduc~ vita~
Pyridoxine (Vitamin 86) B12 and have to depend on animal sources including dairy
products, eggs and meat. Organs such as liver, kidney,
Rich sources of vitamin B6 include yeast, sunflower seeds,
heart and muscle meat, clams and oysters are rich sources
wheat germ, unpolished rice/ cereals, soya beans and
walnuts. Primary dietary deficiency is rare but secondary of vitamin 6 12 •
deficiency can occur in malabsorption states and with Absorption and metabolism: Vitamin B12 b~ds t~ intrinSic
drugs like isoniazid. factor, a glycoprotein produced by the gastric panetal cells,
-120
~~~~~~~~~~~~~-..!E~s~s~e~n~tl!a~l~P!ed~l~a~tr~lc~s!.-~~~~~--~~~~~~~--~
. e it acts as a coenzyme fornol'Illal ::
and the ~ompl~x is absorbed by specific receptor-mediated 11
maintenance ~~e ss,~~~sis. Leafy vegetables such as
pro~ess ~the ileum. Absence of intrinsic factor results in
DNA and R . Y s lettuces, dried beans and peas
an i~a?ihty to ab.sorb ingested vitamin B12 known as spinach, turmp greed:~ts sunflower seeds and' cert;i;~ .
pern~c10us anerma. Passive diffusion accounts for a fortified cerea1 pro / ....,,
fraction of total absorption, but may be useful in the fruits and vegetables are rich sources. ..
~ana?ement of p~rnicious anemia with megadoses of the . t The recommended daily allowance of foUc
vi~amm. Cobalamm undergoes enterohepatic recirculation; R~qdiure~ne1f1 s.m· 25 µgin infancy to 200 µg by adolescence
this process accounts for a long half-life of the vitamin. aci vanes ro . ·
Vitamin B12 is transported in plasma bound to .r .
D e1 ic1ency:
Fola te is absorbed in the small intestine
· t t ·
~anscobalamin II. The average total body pool in an adult Deficiency can occur in malabsorpt10n s a es such as
is enough to sustain daily vitamin B12 needs for several · t om· testinal infections, short bowel syndrome
years. ch romc gas r · k f
and celiac disease. Preterm babies are at ns o folate
deficiency due to increased tissue demands a~d lack of
Requirements: The recommended intake of vitamin B
adequate stores as maternal trans~er occurs 1~ the last
for infants is 0.3 µg/ day. Older children should recei;~
trimester of pregnancy. Children with hemoly.hc anemia
0.5-1.5 µg/day and adolescents 2.0 µg/day.
have high folate require~ents due to m~r.eased
D~fici_ency:_ Vita~ B12 deficiency can occur in patients erythropoiesis predisposing them to . def1c1ency.
with impaired intestinal absorption due to defects in Anticonvulsant drugs increase the catabobsm of folate
· intrinsic factor, or distal ileal disease. True dietary vitamin leading to secondary deficiency. ··.
B12 deficiency occurs in persons who follow vegan diets Deficiency of folate impairs DNA synthesis, limits cell
containing no animal or fish products. Content of vitamin division and affects normal growth and repair of tissues.
B12 in breast milk is determined by maternal intake. Hence, The tissues that have the fastest rate of cell replacement
exclusively breastfed infants of strict vegan mothers can are affected first. Erythropoiesis is hindered, resulting in
beco~e v!tamin_B 1 ~ defi~i~1_lt over a period of time
I
megaloblastic anemia.
especially if wearung is not m1tiated at an appropriate age. Maternal deficiency of folate, during pregnancy, is
Vitamin Bi2status is assessed by measurement of serum implicated in neural tube defects. Periconceptional folate
cobalamin levels, with values below 150 pg/mL indicative supplements, begun 1 month before conception and
of negative vitamin B12 balance. Plasma levels of continued for 3 months after, is recommended to reduce '
methylmalonic acid and homocysteine are increased ~~k .
because of block in vitamin B12-dependent steps of In patients with megaloblastic anemia, it is imperative
metabolism. to exclude and treat vitamin B12 deficiency before treating
Characteristic features of vitamin B12 deficiency include with fo_la_te. Otherwise the neurological signs of vitamin
progressive demyelination, which begins in peripheral B12 ~~flc1e~cy may develop and progress irreversibly. .
nerves and progresses to involve the posterior and lateral Deficiency is corrected using folic acid at a dose of 0.5-1
columns of the spinal cord and central nervous system mg/ day orally for 3-4 weeks. .
(subacute combined degeneration). These lesions are
possibly due to a generalized methyl group deficiency in Vitamin C
the nervous system and faulty myelin production. ;.'itamin C (L-a~corbic acid or ascorbate) plays many .
Secondary folate deficiency results in megaloblastic rmportant roles m the body; it is needed for formation of ·'·
anemia, neutrophil hypersegmentation and thrombo- protocollagen and maintenance of norma1 connec t'ive .
cytopenia. .
v ·t · c . healing and bone (os t e01'd) f orma t'ion.· .·.
tissue, wound
Diagnosis of deficiency: The anemia is macrocytic and I amm is a. reducing agent required for ox1'd a ti'on·..!. ,
.
red uc tion reactions including the hyd . f . .,
nucleated RBC showing megaloblastic morphology may d 0r Add' . roxy1ation o 1ysme ...
and P~ me-_ . ittonally, it reduces ferric to ferrous state .:·
be seen in blood. Levels of red cell folate are low; serum
LDH levels are elevated.
1
an . ~ ps m iron absorption in the ut Due to its ..
antioxidant properties it stabi'l' g · h :5
. , ' izes a number of ot er : ·
Treatment: Deficiency is treated with parenteral adminis- compounds, mcludmg vitamin E and f li . :
unlike other animal 1 k o c acid. Humans, .
trations of vitamin B12 (1 mg). Reticulocytosis is seen
within 2-4 days. Patients with neurologic involvement oxidase) required to:' ac th~ enzyme (gulonolactone ",.
conversion of gl t b'c , .
require daily therapy for 2 weeks. acid hence vitamin c is b . ucose o ascor i ":..
must e obtamed from the diet. ·· ,·
Sources: Rich sources of vitamin C . . ::';
Follc Acid (Pferoylmonoglutamic Acid) fruits (oranges, grapefruit, lime anmclude fresh citrus :~
Folic acid is the parent compound of a group of naturally vegetables (cabbage, cauliflo ~ gooseberry) and -~j
occurring, structurally related compounds known as the Much of the vitamin is lost. Wer, spinach, cucumber). ·.
folates. Folic acid is essential for normal growth and stable in canned and froz m fcooking and s t orage, b u tis ~1~_
en oods. Human milk is rich ·>
..
,T•
~
Micronutrients In Health and Disease 1121 -
I
epiphyses Is surrounded by a thin white line (Wimberger ring
the sternum are often apparent. Scurvy can result in sign) (arrow heads)
cerebral hemorrhage or hemopericardium and is
potentially fatal, if left untreated. absorption can adapt to a wide range of dietary calcium
intakes, varying from 10 to 80% of available calcium.
Diagnosis of scurvy: The diagnosis is made by presence Calcium absorption also depends on the interaction of
of characteristic physical findings and history of calcium with other dietary constituents, including fiber,
inadequate dietary intake of vitamin C. X-rays of long phytate, oxalate, fat and lactose.
bones show a ground glass appearance with thinning of The main sources of calcium for infants are milk and
cortex (pencil thin cortex). An irregular thickened white dairy products, with smaller amounts derived from grains
line appears at the metaphysis (white line of Frankel), and fruits once solid foods are introduced. Children
representing the zone of well-calcified cartilage. There is consuming strict vegetarian diets may develop calcium
a zone of rarefaction proximal to this line, which represents deficiency, either alone or in combination with vitamin D
poorly formed trabeculae (Triimmerfeld zone). The lateral deficiency. Strict vegetarian diets may provide as little as
part of the rarefaction appears as a triangular defect call~d 250 mg of calcium per day and include generous amounts
Pelken spurs. The epiphyses are surrounded by a thin of substances that inhibit calcium absorption, such as fiber
white line (Wimberger ring sign) (Fig. 8.8). and phytates. Secondary calcium deficiency may develop
Titerapy for scurvy: Therapy with 10~2~ mg of vitamin .c in association with steatorrhea, chronic malabsorption
orally or parenterally prompts rapid improvement m syndromes, or intestinal or renal abnormalities of calcium
symptoms and resolution of the radiological signs. Daily metabolism.
intake of 100 mL of orange juice or tomato pulp has the The recommended intake of calcium is 200 mg and
same effect. 260 mg/day for infants aged 0-6 and 6-12 months,
respectively. Children aged 1 to 10 years require an intake
of 500 to 800 mg/day. During the pubertal growth spurt,
MINERALS
calcium requirements are as high as 1000 to 1200 mg/ day.
Calcium Pregnant and lactating women require 400 mg/ day.
Calcium is the most abundant mmeral in the body and is Calcium deficiency may cause tetany characterized by
located primarily (98%) in bone. Calcium is essential for muscle cramps, numbness and tingling in limbs. Rickets
the coagulation cascade, nerve conduction and muscle and osteoporosis may occur with chronic deficiency.
stimulation. Intestinal absorption of calcium varies
inversely with intake and is regulated by l,25(0H)D3, Magnesium
which controls the synthesis of calcium-binding protein Magnesium is essential for reactions contro~ling
at the brush border. In the presence of vitamin D, calcium carbohydrate metabolism, membrane transport and signal
-122 Essential Pediatrics
adolescents, pregnant and
transmission contributing to the action of more than Deficiency: Infants, children, ' d d m""nd of zinc due to
. I · crease e "
300 enzymes. Over 80%, of the total body magnesium is in lnclatmg women i~ve in 'h . Deficiency is also seen
bone and skeletal muscle. Rich somccs of magnesium nctivc growth and tissue synt esis,. b rption syndromes
·1· n nnd ma a so ,
include legumes, nuts, bananas nnd whole grnins. Ml n part o f ma In.u t n IO ' .... bsorption due to
I' ·1 t kc or poor "
Magnesium is efficiently absorbed in the intestine nnd cnuscd by low c ictary ~ n . 0 f. ·nc in stools can occ:ur
regulation of its balance depends on renal tubular Intestinal disense. Exccs~iv~ los~ a '~vere zinc deficiency
reabsorption. Primary deficiency is common in children with recurrent or chr?nic d.1arr . en. rolon cd intravenous
with protein energy mnlnutrition. Deficiency mny nlso syndromes cnn occur m patients o p g .'
develop secondary to intestinal malnbsorption, excessive feeding. . h .. ·mportant feature of zinc
gastrointestinal losses (fistulne or continuous s uction) or Poor pl~ys1cnl growl is an I - e children. Dela ed
renal losses (tubular disease or diuretics). Clinical depiction in preschool and school ag . .Y
manifestations of magnesium deficiency include . d h ogonadism 1s a promment
sexual maturation an YP h f
irritability, tetany and hypo- or hyper-reflexia and cardiac feature of zinc deficiency in adolescents. 0. t er ea~r~
arrhythmias in severe cases. Magnesium requirements in include anemia, anorexia, diarrhea, alopec1a, de~matitis,
the first 6 months range between 40 and 50 mg/ day; impaired immune function, poor wound healing and
60 mg/day for 6-12 months and approximately 200 mg/ skeletal abnormalities. .
day for older children. d
Acro erm atitis enteropathica is an autosomal recessive
db . . d
disorder of severe zinc deficiency, cause Y 1mpa1re
TRACE ELEMENTS intestinal absorption due to defect in i~testinal zi.nc
transporter protein. It presents in early mf~ncy, ~1th
Eleven 'major' elements constitute 99% of human body vesicobullous, dry, scaly or eczematous skin les_1ons chiefly
weight: Hydrogen, carbon, nitrogen, oxygen, sodium, in the periorificial (around the mouth and penneum) and
potassium, chlorine, calcium, phosphorus, sulfur and acral areas. Alopecia and eye changes, such as
magnesium. In addition, the body is composed of conjunctivitis, blepharitis and photophobia, may be
through pesticides and contamination of water by pipes in soil especially in mountainous regions due to leaching
and cooking utensils. and erosion. The Himalayan belt and Ganges valley are
areas of severe iodine deficiency in India.
Deficiency: Primary dietary deficiency is infrequent.
Secondary deficiency may develop in malabsorption Recommended daily intake: The recommended iodine
syndromes, liver disease, peritoneal dialysis and other intake is around 90 µg/ day from birth to 5 years of age
conditions causing excessive copper losses. Copper increasing to 120 µg/ day at ages 6-12 years, and
deficiency decreases the life span of the erythrocyte and 150 µg/ day in adolescents and adults. Pregnant and
impairs mobilization of stored iron from liver and bone lactating women require higher amounts (200 µg/ day).
marrow. Features of deficiency are microcytic, hypochromic Iodine is excreted in urine and 24-hour urinary iodine
anemia unresponsive to iron therapy, depigmentation of excretion is a useful measurement of iodine sufficiency in
hair, neutropenia, neurological problems and osteoporosis. a community. Urinary iodine <100 µg/L indicates iodine
Copper transport is disrupted in two human diseases: insufficiency with values <20 µg/L pointing to severe
Wilson disease and Menke disease. Both have defects in deficiency.
copper transporting membrane proteins. Menke disease
is a rare X-linked fatal disorder of impaired copper Iodine deficiency disorders: Nearly 1.5 billion people in
absorption presenting in early infancy with kinky hair, 130 countries around the world live in areas of iodine
skin hypopigmentation, neurological regression and deficiency and are at risk of developing iodine deficiency
seizures. Laboratory findings include hypocupremia, low disorders (IDD). 100 are the commonest cause of mental
plasma ceruloplasmin, neutropenia and anemia. retardation in these populations and are responsible for
an average lowering of IQ scores by 13.5 points compared
Selenium to populations living in iodine-sufficient areas. Goitre is
Selenium is a constituent of glutathione peroxidase, an the earliest manifestation of iodine deficiency and is an
antioxidant in red blood cells and other tissues. Selenium adaptive response to increase thyroid hormone production
also helps maintain normal immune function and is a part under the influence of increased TSH levels, but eventually
of the enzyme type 1-deiodinase which converts thyroxine leads to decompensation in the form of hypothyroidism.
to triiodothyronine. Dietary sources include whole grain, Goitre rates can be as high as 10-30% in endemic
meat, egg, seafood, garlic and mushrooms. Endemic populations suffering from iodine deficiency (Table 8.5).
selenium deficiency results in Keshan disease, a form of Iodine deficiency in the fetus: Maternal hypothyroidism
cardiomyopathy in young children seen in some regions due to iodine deficiency leads to an increased risk of
of China. In combination with iodine deficiency, lack of abortions and stillbirths. The fetal thyroid gland begins
selenium can result in myxedematous endemic cretinism, to function from the second half of gestation. Inadequate
seen in certain parts of Africa. Selenium deficiency may availability of T 4 due to maternal iodine deficiency
be seen in patients on total parenteral nutrition and adversely affects early brain development in the fetus
manifests with macrocytosis, brown hair and whitening leading to permanent manifestations of endemic cretinism,
of nails. including mental retardation, hearing impairment (deaf-
mutism), spastic diplegia and squint.
Chromium
Glucose intolerance, which complicates malnutrition in Iodine deficiency in the neonate: Iodine deficiency affects
young children, has been attributed in part to chromium functioning of the thyroid gland leading to neonatal goitre
deficiency. Chromium acts in glucose homeostasis by and hypothyroidism The brain of the human infant at birth
potentiating insulin action, possibly by facilitating binding has only reached about one-third of its full size and
to its receptor. Symptoms of chromium deficiency are continues to grow rapidly until the end of the second year.
usually in the setting of total parenteral alimentation and The thyroid hormone, dependent on an adequate supply
include glucose intolerance, peripheral neuropathy and of iodine, is essential for normal brain development at this
evidence of disturbed nitrogen and lipid metabolism. critical time. Neonatal hypothyroidism persists into
infancy and childhood, if the deficiency is not corrected
Iodine and results in retardation of physical and mental
development.
Iodine, a micronutrient present in small quantities in the
thyroid gland, is essential for the formation of thyroid Iodine deficiency in children: Moderate iodine deficiency
hormones thyroxine (T 4) and triiodothyronine (T3). is associated with abnormalities in psychoneuromotor and
Thyroid hormones play a key role in body growth and intellectual development of children who are clinically
brain development, especially in the fetus and first three euthyroid, but who do not exhibit other features of
years of postnatal life. endemic cretinism (Table 8.5). Some patients may show
Iodine is most commonly found in sea water and sea goiter (Fig. 8.9) (see Chapter 18). Studies in moderately
food/plants are rich sources. Iodine is relatively deficient iodine-deficient areas indicate that fine motor skills and
-124 Essential Pediatrics
. bl solving improved in school children a
. ft
I
serious and often irreversible (Chapter 13). .,
. .'
Suggested Reading
• Elder CJ, Bishop NJ. Rickets. Lancet. 2014 May 10;383(9929):1665-76:
• Global Consensus Recommendations on Prevention and
Management of Nutritional Rickets. J Clin Endocrinol Metab 2016
Feb;101(2):394-415. .
• ~MR 2010. Nu.trient requirements and recommended diet~
owanc~ for Indians. Report of the Expert Group ofICMR, New Delhi.
• ~Cw~dRel'D1eftarNINy
guidel~nes for Indians. ninindia.org/Dietary
. mes or webs1te.pdf
6
Clin North Am. 2009 Oct;S (S):l0 5-~gnormalgrowth.Pediatr
3
• Suskind DL. Nutritional deficiencies d .
. ... I
'!
chapter
9
Newborn Infants
Ramesh Agarwal • Vinod K Paul • Ashok K Deorari
Newborn infants are unique in their physiology and the 40% occur within first 24 hours, half within 72 hours and
health problems that they experience. Neonatal period is three-fourths within one week of birth. Health of the
characterized by transition to extrauterine life and rapid mother and care during pregnancy and at childbirth has
growth and development. Newborn period, just first profound influence on neonatal outcome. As noted in
28 days of life, carries the greatest risk of mortality. Despite Chapter 1, decline in neonatal mortality is critical to
being less than 2% of total period of under-5 childhood, achieve national health goals. The stagnant early neonatal
the newborn period accounts for over half of under-5 child mortality is a cause for concern.
mortality. Good care, therefore, not only improves
survival of children but lays foundation of optimal long- Definitions
term physical and neurocognitive development. Neonatal period: From birth to under four weeks (0 to 27
Newborn health is the key to child health and survival. days or 1 to 28 days, depending on whether the first day
In india (SRS 2012), neonatal deaths account for 56% of has been taken as day 0 or day 1 of life) of age. An infant
under-5 (Fig. 9.1) and 69% of infant deaths. First week is called a neonate during this phase. First week of life (<7
deaths (<7 days; early neonatal deaths) alone account for days or <168 hours) is known as early neonatal period.
45% of total under-5 deaths. Preterm birth complications Late neonatal period extends from 7th to <28th days.
account for 35% of all neonatal deaths and constitute the Postneonatal period: Period of infancy from 28 to
most important cause of neonatal mortality. Bacterial <365 days (<1 year) of life.
infections (sepsis, pneumonia and diarrhea) contribute to
21% of neonatal deaths. Other causes of neonatal mortality Weeks ofgestation refer to completed weeks of gestation,
are birth asphyxia and congenital malformations. Almost e.g. 36 weeks gestation, refer to range of gestation from
three-fourths of all neonatal deaths occur among the low 36 weeks 0 day to 36 weeks and 6 days.
birth weight newborns. Of all the neonatal deaths, about Perinatal period: Perinatal period extends from 22ndweek
of gestation (>154 days or fetal weighing 500 g or more)
~--- Neonatal
pneumonia 2% to less than 7 days of life.
Neonatal sepsis and Live birtli: A product of conception, irrespective of weight
meningitis 10%
or gestational age, that, after separation from the mother,
shows any evidence of life such as breathing, heart-beat,
pulsation of umbilical cord or definite movement of
Meningitis voluntary muscles.
2% Fetal deatli: A fetal death is a product of conception that,
Malaria
1% after separation from the mother, does not show any
evidence of life.
Stillbirth: Fetal death at a gestational age of 22 weeks or
more or weighing 500 g or more at birth.
Term 11eo11ate: A neonate bom between 37 and 42 weeks
Other Congenital
(259-293 days) of gestation.
neonatal 5% malformations Preterm 11eo11ate: A neonate bom befo_re 37 ":eeks (<~ 9
4%
3 days) of gestation irrespective of the birth weight.
Fig. 9.1 : Causes of under-5 deaths ot global level (20l )
125
b
11111 126 Essentlnl Podiatries
infants may not improve with ventilation alone. The Suction equipment
combination of oxygenation and correction of metabolic Mechanical suction
acidosis would be necessary to open the pulmonary Suction catheters 10, 12 or 14 F
arterioles to improve pulmonary blood flow. Meconium aspirator
· Bag and mask equipment
cardiac Function and Systemic Circulation
Neonatal resuscitation bags (self-inflating)
Asphyxia causes redistribution of blood flow to preserve Face-masks (for both term and preterm babies)
blood supply to vital organs. There is vasoconstriction in Oxygen with flow meter and tubing
the bowel, kidney, muscles and skin while the blood flow
Intubation equipment
to the heart and brain is relatively preserved (diving-in
reflex). Laryngoscope with straight blades no. O (preterm) and no. 1
(term)
As asphyxia is prolonged, myocardial function and
Extra bulbs and batteries (for laryngoscope)
cardiac output too deteriorate and blood flow to all the
Endotracheal tubes (internal diameter of 2.5, 3.0, 3.5 and
organs is further reduced. This sets in the stage for
4.0 mm)
progressive organ damage.
Medications
Preparing for Resuscitation Epinephrine
With careful consideration of antepartum and intrapartum Normal saline or Ringer lactate
Naloxone hydrochloride
risk factors, asphyxia can be anticipated in up to only half
of the newborns who will eventually require some form · Miscellaneous
of resuscitation. In others, the need for resuscitation can Linen, shoulder roll, gauze
come as a surprise. Therefore, each delivery should be Radiant warmer
viewed as an emergency and basic readiness must be Stethoscope
ensured to manage asphyxia. Syringes 1, 2, 5, 10, 20, 50 ml
Preparation for delivery should include: Feeding tube 6 F
i. Assessing perinatal risk factors, ensuring availabi~ity Umbilical catheters 3.5, 5 F
of at least one person who is capable of undertaking Three way stopcocks
full resuscitation and whose sole responsibility is that Gloves
of newborn only. In an anticipated need for resuscita-
tion, there may be need of more than one person.
sequential time points following birth can reflect how well
ii. All resuscitation equipment immediately available and the baby is responding to resuscitative efforts. Extended
in working order (Table 9.1) · . . Apgar scores should be obtained every 5 minutes for up
iii. Ensuring a good teamwork and proper commurucation to 20 minutes, if the 5-minute Apgar score is less than 7.
between teammates.
TABC of Resuscitation
Rote of Apgar Scores In Resuscitation
The components of the neonatal resuscitation can be
The Apgar score is an objective method of evaluating the summarized as TABC:
newborn's condition (Table 9.2). It is generally performed
T-Temperat11re: Provide warmth, dry the baby and remove
at 1 minute and again at 5 minutes after birth. However,
the wet linen.
resuscitation must be initiated before the 1-minute .score
is assigned. Therefore, the Apgar score is not used to guide the A-Airway: Position the infant, clear the airway, if required
:I ' (by wiping or suction of baby's mouth and nose).lf
resuscitation. . ch 1 (ET) b t
· · making
While the Apgar score is not useful for dec151on necessary, insert an endotra ea tu e o ensure an
at the beginning of resuscitation, the change of score at open airway.
_ ........'"...... ~ -.~-- -• ..-. ·- - -. "'7·-.-:-· ... . 1·· - . ......... ----::'-- ..,-;-r:~:---:?c~
~. ·- ---=-...-·-·:--·~·......,.,""-~
R ....... •-.•
Antenatal counselling
Team briefing and equipment check
l
~ Infant stays with mother for routine
care: warm and maintain normal
Term gestation? Yes
good tone? temperature, position airway, clear
Breathing or crying? secretions if needed, dry,
Ongoing evaluation
No
Warm and maintain normal temperature,
position airway, clear secretions if
needed, dry stimulate
Yes
Yes
Position and clear airway
PPV
•
Sp02 monitor
Sp02 monitor
Supplementary 0 2 as needed
Consider ECG monitor
Consider CPAP
,.._.....,_ _ _t,_ _ __
No
_____.._< HR below 100/min? .--- - - - Postresuscitation care
Team debriefing
Yes
No 1 min 60-65%
...__ _ _-< . HR below 60/min? : 2 min 65-70%
3min 70-75%
Yes
4min 75-80%
Intubate, if .n ot already done 5min
Chest compressions 80-85%
Coordinate with PPV 10 min 85-95%
100% 0 2
· · ECG monitor
Consider emergency UVC
HR below 60/mln?
Yes
IV epinephrine
If HR persistently below· 60/min
Consider hypovolemla
Consider pneumothorax .
Fig. 9.2: The algorithm of n9:0natal resuscitation. CPAP continuous positive airway pressure; PPV POsitiv · · ·
saturation of oxygen (Adapted with permission from American Academy of Pediatrics 2015). · e Pressure ventilation; sp02
Newborn Infants 1129 -
iii. Good muscle tone? (flexed posture and active The secretion can be removed from the airway by
movement of baby denotes good tone) wiping the nose and mouth with a clean cloth or by
If a~wers to all the three questions are 'Yes', the infant suctioning with a bulb syringe or suction catheter. The
stays with mother and receives just "Routine care". Routine mouth is suctioned before nose ('M' before 'N') to ensure
care consists of four steps: the infant does not aspirate, if she should gasp when the
i. Warmth: Provided by putting the baby directly on the nose is suctioned. If the infant has copious secretion from
mother's chest in skin-to-skin contact. the mouth, the head should be turned to the side. This
will allow secretions to collect in the side of mouth, where
ii. Cl.earing of afr;vay, if required: Position the baby and
wipe the baby s mouth and nose using a clean cloth. they can be easily removed.
No need to suction routinely. For suctioning, the size of suction catheter should be
iii. Dry the baby 12 or 14 Fr. The suction pressure should be kept around
80 mm Hg (100 cm H 20) and should not exceed 100 mm
iv. Ongoin? evaluation for vital parameters. Helping
Hg (130 cm H 20). One should not insert the catheter too
mother m breastfeeding will facilitate easy transition
deep in mouth or nose for suction as it may stimulate
to extrauterine environment.
posterior pharynx producing vagal response resulting in
If answer to any of the three questions is "No", the baby
bradycardia or apnea.
requires at least some resuscitation. After cutting the cord,
the baby should be subjected to a set of interventions
Dry ond Stimulate
known as initial steps.
After suctioning, the baby should be dried adequately
Initial Steps using prewarmed linen to prevent heat loss. The wet linen
should be removed away from the baby. The act of
Warmth suctioning and drying itself provides enough stimulation
The baby should be placed under the heat source, to initiate breathing. If the newborn continues to have poor
preferably a radiant warmer. The baby should not be respiratory efforts, additional tactile stimulation by gently
covered with blankets or towels to ensure full visualization rubbing trunk, back and extremities for several seconds
and to permit the radiant heat to reach the baby. may be provided to stimulate the breathing. However,
one should not waste too much of time in providing tactile
Positioning stimulation.
The baby should be placed on her back or side with the
neck slightly extended. This helps in keeping the airway Management of Infant Born through
open and facilitates breathing. Care should be taken to Meconlum-Stained Liquor (MSL)
prevent hyperextension or flexion of the neck, since either A baby born through meconium-stained liqor (MSL) may
may interfere with respiration. aspirate the meconium into the trachea and lungs. The
To help maintain the correct position, one may place a procedures like intrapartum suctioning of the mollth and nose
rolled blanket or towel under the shoulders of the infant before deliven; ofthe shoulders and postnatal tracheal Sllctioning
elevating her by 3,4 or1 inch off the mattress. This 'shoulder of non-vigorous babies are no more recommended.
roll' is particularly helpful, if the infant has a large occiput If a term baby born through MSL is vigorous (breathing
resulting from molding, edema or prematurity (Fig. 9.3). well and good tone), the baby is provided initial steps.
The gentle suction of mouth and nose may be required to
Clear Airway, If Necessary clear airways and the baby is kept with mother with
The appropriate method for clearing the airway will continued observation for development of any respiratory
depend on the presence or absence of meconium. difficulty. If non-vigorous (feeble breathing or low tone),
the baby is provided initial steps under radiant warmer
and PPV is provided, if required.
Evaluation
After providing initial steps, the baby should be evaluated
by assessing respiration, HR and color (or oxygen
saturation by pulse oximetry).
Respiration is evaluated by observing the infant's chest
movements. HR can be assessed by auscultating the heart
or by palpating the umbilical cord pulsation for 6 seconds.
The number of beats or pulsation is multiplied by 10 to
obtain the HR per minute (e.g. a count of 12 in 6 seconds
Fig. 9.3: Rolled towel under the shoulders is an HR of 120 per minute). Color is evaluated by looking
- 130 ~~~~~~~~~~~~___:E=s~s~e~n~tl~a~l~Pe~d~i~at~r~ic~s~~~~~~~~~~~~~~--~
ended that term babies should '
at tongue, mucous membranes and trunk. A blue hue to It is therefore, reco mm
the lips, tongue and central trunk indicates central . .~ d ai'r resuscitation. Ideally, oxygen
be m1tiate on room .
cyanosis. Presence of cyanosis in extremities (acrocyanosis) .
saturation s ouh Id b e monitored by pulse
. . oxunetry and
does not have any significance. d I' y should be titrated to mamtam the oxygen
• If the baby has good breathing, HR 100/min or more oxygent. e ~verthe targeted range (Fig 9.2). In absence of
satura 10n m · db
and no cyanosis, then she does not require any pulse ox1m . etry, room air should be substitute
. y.100%
additional intervention and the baby should be oxygen, if the baby fails to improve (unprovement m HR
monitored frequently. and breathing) by 90 seconds. .
• If the baby has labored breathing or persistent central PPV in preterm babies (<35 weeks) ts recommended
cyanosis, administration of CPAP in preterm babies and using intermediate concentration of oxygen (_21 to 30%).
supplemental oxygen in term babies is recommended.
The oxygen concentration should be _titrated by
Baby should have its oxygen saturation monitored and
supplemental oxygen is titrated to achieve the targeted continuously monitoring of oxygen saturation by pulse
saturations (Fig. 9.2). oximetry. BMV is indicated, if:
• If the baby is apneic, has gasping breathing or heart i. The infant is apneic or gasping
rate below 100 min, positive pressure ventilation (PPV) ii. HR is less than 100 beats per minute
is needed. Jn suspected or confirmed diaphragmatic hernia, bag and
Supplemental Oxygen
mask ventilation is contraindicated.
Central cyanosis requires supplemental oxygen, which can Procedure
be provided by an oxygen mask or oxygen tube held in
The infant's neck should be slightly extended to ensure
cupped hand over baby's face or by flow inflating bag and
mask. The flow of oxygen should be at least 5 L/minute. an open airway. The care provider should be positioned
at head end or at the side of baby so as to have an
Positive Pressure Ventilation (PPV) unobstructed view of infant's chest and abdomen. Select
PPV is usually given by using a self-inflating bag and face an appropriate sized face mask that covers the mouth and
mask (bag and mask ventilation or BMV). The self- nose, but not eyes of the infant (Fig. 9.5). The face mask
inflating bag is easy to use as it reinflates completely should be held firmly on face to obtain a good seal. The
without any external compressed source of gas. bag should be compressed using fingers and not by hands.
The resuscitation bag (Fig. 9.4) should have a capacity PPV is the single most effective step in babies who fail to
of 240 to 750 mL. The bag is attached to sources of oxygen breath at birth. Ensuring adequacy of ventilation is the most
and air and a blender which provides a desired important priority in such babies.
concentration of supplemental oxygen.
Oxygen should be treated as a drug. Both too little and
too much of oxygen are bad for the baby. Even a brief
exposure to high concentration of oxygen can have
detrimental effect on the baby. Studies have shown that
term babies resuscitated with room air compared to 100%
oxygen have better survival and long-term outcomes. The
evidence in favor or against the use of oxygen in preterm
babies is yet lacking.
Pressure release
(pop-off) valve
Patient outlet
Ag. 9.4: Self-Inflating bag (Adapted with permission from MP Fig. 9.5: Properly fitting mask (Ad t
2005) 2005) ap ed With permission from NJ'
Newborn Infonta 1131 -
One Two Two Three
Throo Ono
(Squeez.o) (Rolonso ... , •.) (Release • ••.••)
(Squoozo)
Rg. 9.6: Correct rhythm of providing positive pressure venlllallon (Adapted with permission from American Academy of Pediatrics
2005)
_
-· _ , _.._. Procedure
The infant's head should be in midline and the neck kept
Fig. 9.7: Chest compression with thumb technique (Adapted slightly extended. The laryngoscope is held in the left hand
with permission from AAf' 2005) between the thumb and the first three fingers, with the
blade pointing away from oneself. Standing at the head
To determine efficiency of chest compressions, the end of the infant, the blade is introduced in the mouth
carotid or femoral pulsation should be checked and advanced to just beyond the base of the tongue so
periodically. that its tip rests in the vallecula. The blade is lifted as
Possible complications of chest compressions include shown in Fig. 9.8 and landmarks looked for; the epiglottis
broken ribs, laceration of liver and pneumothorax. and glottis should come into view. The glottic opening is
surrounded by vocal cords on the sides. Once the glottis
Evaluation and vocal cords are visualized, the ET is introduced from
After a period of 30 seconds of chest compressions, the the right side of the mou th and its tip inserted into the
heart rate is checked.
Table 9.4:..Appropriate endotracheai"tU~·~:z~- ""1
HR below 60. Chest compressions should continue along
with bag and mask ventilation. In addition, medications /nner diameter Weight Gestational age
(epinephrine) have to be administered. ·of tube (mm) (g) (weeks)
2.5 <1000 <28
HR 60 or above. Chest compressions should be dis-
3.0 1000-2000 28-34
continued. BMV should be continued until the heart rate
3.5 2000-3000
is above 100 beats per minute and the infant is breathing 34-38
spontaneously. 4.0 >3000 >38
Endotracheal Intubation
Endotracheal (ET) intubation is required only in a small
proportion of asphyxiated neonates. Intubation is a
relatively difficult skill to learn and it requires frequent
practice to maintain the skill.
Indications
The indications of ET intubation are: (i) when tracheal
suction is required (in non-vigorous babies born through
MSL), (ii) when prolonged BMV is required, (iii) when
BMV is ineffective, and (iv) when diaphragmatic hernia
is suspected. The other conditions where ET intubation Correct
Incorrect
may be considered are: before starting chest compressions Fig. 9.8: Direction of pull on the laryn with
and for administering epinephrine. permission from MP 2005) goscope (Adapted
133
glottis m:~ ~e v~cal cord guide is at the level of the glottis, LEVEL OF NEWBORN CARE
thu.s pos1tiorung it half way between the vocal cords and
canna. Level-l 11nits: Provide care to normal term newborns and
stable newborns of 35 to 36 weeks gestation. These units
Medications stabilize small and sick infants and transfer them to higher
The majority of infants requiring resuscitation will have a level facilities.
response to prompt and effective ventilation with 100% Level-2 units (special care nursery): Look after babies born
oxygen. Only a few require medications. at or after 32 weeks of gestation or weighing 1500 gm or
Medications used in resuscitation include epinephrine more at birth or those with moderate sickness. These units
and volume expanders (Table 9.5). Sodium bicarbonate can provide CPAP and ventilation for brief periods. They
and naloxone are indicated only for special circumstances. can serve as step-down units for level-3 and level-4 care.
There is no role of atropine, dexamethasone, calcium, Level-3 units (intensive care units): Provide care to babies
mannitol and dextrose for newborn resuscitation in the less than 32 weeks and 1500 gm and ones with critical
delivery room. illnesses. These units can offer full range of respiratory
support.
Route of administration: Since veins in scalp or
extremities are difficult to access during resuscitation, Level-4 care includes full range of advanced subspecialities
umbilical vein is the preferred route. No intracardiac including options of cardiac surgery.
injection is recommended. The Indian health system defines level of care in
For umbilical vein catheterization, 3.5 Fr or 5 Fr following manners:
umbilical catheter is inserted into the umbilical vein such Newborn care corner (NBCC): All birthing facilities must
that its tip is just inside the skin surface and there is free have NBCC to provide resuscitation (care at birth) and
flow of blood. Direct injection into the umbilical cord is care to well babies. These units identify and refer at risk
undesirable. and sick neonates to higher facilities.
Epinephrine may be injected directly into the tracheo- Newborn stabilization units (NBSW: In addition to NBCC
bronchial tree through ET. Since absorption is erratic, this services, these units provide sick newborn care to babies
method is to be used, only if venous access cannot be above 1800 gm.
obtained. The drug is injected by a syringe or a feeding Special newborn care 11nits (SNCU): In addition to services
tube (5 Fr) into the endotracheal tube, flushed with 0.5 mL provided by NBCC and NBSU, these units provide care
of normal saline and dispersed into the lungs by PPV. to babies <1800 gm and limited ventilation facilities.
Indications CARE OF NORMAL NEWBORN BABIES
Use of adrenaline is indicated, if HR remains below 60
Care at Birth
despite adequate ventilation and chest compressions for
30 seconds. · Standard precautions and asepsis at birth: The personnel
attending the delivery must exercise all the universal/
Suggested . Reading standard precautions in all cases. All fluid from the babyI
• Textbook of Neonatal Resuscitation.; 7th ed. American Academy mother should be treated as potentially infectious. Gloves,
· of Pediatrics and American Heart Association, 2015 masks and gowns should be worn when resuscitating the
- 134 I Essential Pediatrics
I
decreases the pain and bleeding in the mother. The baby sensitivity. Electronic weighing scales are ideal. Zeroing
should be observed ~uring. the transition period and of the machine should be performed. The baby is then
appropriately clothed including caps and socks. gently placed on the weighing machine and the weight is
Delayed clamping of umbilical cord: Umbilical cord recorded.
clamping must be delayed for at least 30 seconds (in term First examination: The baby should be thoroughly
as well as preterm babies) in order to allow transfer of examined at birth from head to toe and the findings should
additional amount of blood from placenta to the infant. be recorded in neonatal record sheet. Examine midline
This delayed cord clamping in term babies is asso~ia.ted structures for malformations (e.g. cleft lip, neck masses,
with improved hematologic status, iron status and clinical
chest abnormality, omphalocele, meningocele, cloaca!
anemia at 2 to 6 months. In preterm infants, delayed cord
abnormality). Special attention should be given to identify
clamping is associated with reduced IVH and other
and do~ument the patent anal opening. There is no need
morbidities. However, if the baby is asphyxiated at birth,
for routine passage of catheter in the stomach nostrils and
cord should be clamped immediately after birth and
resuscitation is initiated without any delay. the r~ctum for detection of esophageal atr~sia, choanal
atres1a and anorectal malformation, respectively. The baby
Cleaning of baby: The baby should be dried and cleaned sh?uld be examined for presence of birth injuries. The
at birth with a clean and sterile cloth. The cleaning should axillary te.mpe.rature of the baby should be recorded before
be gentle and should only wipe out the blood and the the baby is shifted out from the birthi
1
ng pace.
meconium and not be vigorous enough to remove the
Initiation of breastfeeding: Brea tf d · h Id be
vemix caseosa (whitish greasy material on the skin). The initiated within one hour of birth sThee hmgl hs ou 'd r
vernix protects skin of the infant and helps maintain . h · e ea t prov1 e
sh ou ld assist t e mother to put th b t
temperature. This gets absorbed on its own after sometime. ·
1rrespechve· of the mode of de!. e aby on breas .
Clamping of the cord: The umbilical cord should be clamped counseling alone witho t . ivery. Breastfeeding
result in high rates ofus proactive sup port is · unlikely to
at 2-3 cm away from the abdomen using a commercially uccessful bre £
available clamp, a clean and autoclaved thread or a sterile support is needed in primi as - eed.mg. Extra
t
para mothers and small babies.
rubber band (Fig. 9.9). The stump should be kept away Vitamin K: It should be admini t ·
from the genitals to avoid contamination. The cord should (0.5 mg for babies less than s ered to all the bab~es
1000
be inspected every 15-30 minutes during initial a few hours more than 1000 g). It is preferable~;nd 1. ~g for ~abi~
after birth for early detection of any oozing. K1preparation, however, if not . admm1ster v1tarru
available, vitamin K3 may
I 1as
be ~d.mirub'steb~ed. Vitamin K3 can cause hemolysis in G6PD • The newborn is not having significant jaundice or any
deficient a ies.
other illness requiring closer observation by a health
Commrmication witlt tlte family: Before leavin the birth provider.
place, the health profes~ional should commun~cate with • The mother has been counseled regarding routine
the mother and the fanuly members. The following facts newborn care and her queries are answered.
should be clearly told to the family: (i) d f h b b • Follow-up advice should be communicated to the
")b' th . ht("') gen ero tea y,
~n.. ir. wefig ' l11 w~ll-be~g of the baby, (iv) need for mother. Babies, particularly born to primigravida
J.Illhahon
. o breastfeedmg
. withm' one h our an d need for mothers should be called for follow-up visit at 48 hours
continued observation for any problem. of discharge, if discharged before 72 hours.
Rooming in: Normal newborn should not be separated • Parents have been explained the foJJowing 'danger
from the m~ther. In the initial a few hours of life, the baby signs' when they need to bring the baby to the hospital:
is ~~ry active and co-bedding of the baby with mother i. Difficulty in feeding or poor feeding
facilitates early breastfeeding and bonding. Studies have ii. Convulsion
shown that any separation during initial hours may have iii. Lethargy (movement only when stimulated)
a deterimental effect on successful breastfeeding. iv. Fast breathing (RR >60/min)
v. Severe chest indrawing
Care of Baby beyond a Few Hours after Birth vi. Temperature of more than 37.5°C or below 35.5°C
Care of tit~ cord: The um?ilical stump should be kept dry • A date for follow-up has been assigned. A normal
and devoid of any application. The nappy of the baby newborn with adequacy of breastfeeding and no
should .be ~olded well below the stump to avoid any significant jaundice by 72 hours of age can be seen at
contammation. 6 weeks of age. In presence of any high-risk factor (e.g.
low birth weight, prematurity significant jaundice, or
Exclusive breastfeeding: A proactive and a systematic feeding not established), the baby should be seen within
approach should be followed to initiate, support and 2-3 days of discharge.
I
maintain breastfeeding. The various advantages of the
breastfeeding should be discussed with the mother to Common Parental Concerns
motivate her. Availability of dedicated lactation nurse or • Weight loss in first week: Normally, babies lose 8-10% of
counsel or significantly improves the chances of successful birth weight in the first week of life which is regained
breastfeeding. by 7-10 days age. Subsequently, there should be a gain
Position of sleep: Evidence has linked prone position to of 20 to 40 g per day.
the occurrence of sudden infant death syndrome (SIDS). • Crying during micturition: The sensation of a full bladder
All healthy term newborns should be put to sleep on their is uncomfortable to many babies who cry before passing
back (supine position). urine and they quieten as soon as the act of rnicturition
starts. Crying during passage of urine as opposed to
Traditional practices that should be discouraged: The before the act of rnicturition should alert clinician to
application of kajal oi: surma in the eyes, putting oil in the the possibility of urinary tract infection.
ear or applying cow-dung on cord must be strongly • Bathing: During the first week, till cord falls off, only
discouraged. sponging is recommended which can be given after the
Timing of discharge in a normal newborn. A normal first 24 hours of life. Later, bathing every 2-3 days is
baby should stay in the health facility for at least 24 hours quite sufficient. A draught-free warm room, warm
and preferably for 48 hours. Smaller babies .or .those ~ith water and quick completion of bath ensure that the baby
feeding problems or sickness should remain in hospital does not get cold during bathing. The head constitutes
as required. . a large surface area of the baby; therefore, it should be
The following criteria should be met in all the babies washed last and dried first. Bathing time can be used
prior to discharge: to inspect baby's cord, eyes and skin for any discharge,
• The routine formal examination of the newborn has rash or redness.
been performed and documented. • Cosmetics: Babies have a sensitive skin and use of
• The newborn is breastfeeding properly. The adequacy cosmetics should be minimized. A low alkalinity, mild,
of feeds can be determined by: non-perfumed/non-medicated soap should b~ us.ed.
- Passage of urine 6 to 8 times every 24 hours Any oil except mustard oil can be ~se~. ~prink~g
talcum powder on babies can result m its inhal.a~on
- Baby sleeping well for 2- 3 hours afte~ fe~ds .
and should be avoided. Avoid products containing
• The newborn has received the immunization as per
boric acid (present in most prickly heat preparati~ns).
schedule.
• Regurgitation (posseting): Babies commonly re~gita~e
• The mother is confident and trained to take care of the
small amount of curdled milk soon after feeding. This
neonate. · .·
• 136 Essential Pediatrics
Skin peeling is another normal skin finding noted is assigned every 5 minutes until 20 minutes or till two
especially in post-term and IUGR babies. Oil massaging successive score are 7 or greater. These scores rapidly
can decrease the flaking and no other intervention is assess the cardiopulmonary status. Apgar scores may be
required. falsely low in ~fants born very preterm and those with
• Diaper rash: There is redness, inflammation and maternal drug intake, sepsis, congenital heart disease and
excoriation of skin in diaper area due to maceration by central nervous system malformations. Low Apgar scores
stools and urine. The problem is more frequent with are poor predictor of long-term neurodevelopmental
plastic nappies. The treatment consists of keeping the outcome.
area dry, avoiding rubbing of the skin for cleaning and
application of a soothing cream. Use of cotton diaper is 1 ~f systemic examination reveals an abnormal finding,
less often associated with this rash. a o~datory evhaluation may be warranted Table 9.6
provi es a sc eme for th ' d
examination of th b e comprehensive history an
e new orn.
EVALUATION OF NEWBORN
Most neonates are born healthy, normal and free from General Observation
disease. Some (approximately 10%) need observation in The least disturbing exaffiin t' . .
nursery. gives an opportunit to a ion should be done first; thlS
Newborn examination yields different information at posture spontane y assess the state of alertness,
'
respiratory distressous activity, co l or, any o b vio· us
different times. Hence, newborns should be examined in
or
should be examined wh th malform a ion. The new orns·
t' b
detail at following time points: (i) soon after birth, (ii) at
24 hours of birth, (iii) before discharge from hospital, and but quiet (happens afte;~-l esy are in light sleep or awake
again (iv) at follow-up visit. 1 A newborn with h .· hour offeed mg
' ).
Immediately after birth, the Apgar scores are assigned YPotorua ha s
in a baby with hYPoxic s an extended posture a
at 1 and 5 minutes (Table 9.2). If the score is less than 7, it the color of the baby; inc~:~phalopathy. A clear note. of
· mg cyanosis, pallor, jaundice
137 .
Table 9.6:- N~wborn history and examination: Format for case presentation
History
General
Mother's name and age, parity, last menstrual period, expected date of delivery
past obstetric history
Past pregnancies: When, gestation, fetal or neonatal problems, current status of children
Antenatal
Number of antenatal visits, tests (hemoglobin; urine albumin, sugar; ultrasound; blood group, VDRL,
HIV), tetanus toxoid immunization, supplements (iron, folic acid, calcium, iodine)
Obstetric or medical
Obstetric complications (toxemia, urinary tract infections, twins/triplets, placenta previa, accidental
complications
hemorrhage); fetal problems (IUGR, hydrops, Rh isoimmunization); medical problems (diabetes,
hypertension); investigations, medications, course
Labor ~resentation, onset of labor (spontaneous/induced), rupture of membranes (spontaneous/artificial),
hquor (clear/meconium stained); duration of first and second stage of labor; fetal heart rate (tachycardia,
bradycardia, irregular)
Delivery Place of delivery, vaginal (spontaneous/forceps/vacuum), cesarean (indication, elective/emergency);
local/general anesthesia; duration of third stage; postpartum hemorrhage
Immediate care at birth Resuscitation; time of first breath and cry; Apgar score; cord care; passage of urine/stool
Feeding history Breastfeeding (when initiated, frequency, adequacy); other feeds
Postnatal problems Feeding problems, jaundice, eye discharge, fever; current problems
Family history History of perinatal illness in other siblings
Past medical problems History of past medical problems, if any
Personal/social history Socioeconomic status, family support
General examination
Immediately after birth Weight, gestation, congenital anomalies, sex assigning, Apgar scores, examination of umbilical vessel,
and placenta
Appearance Overall appearance: Well or sick looking; alert/unconscious
Vital signs Temperature, cold stress; respiratory rate, retractions, grunt/strider; heart rate, palpable femoral
arteries; blood pressure, capillary refill time; cry; apneic spells
Anthropometry Weight, length, head circumference, chest circumference
Gestation Assessment by physical criteria; more detailed assessment by expanded New Ballard examination
Classification by Appropriate/small/large for gestational age; symmetric or asymmetric small for gestational
intrauterine growth age; signs of IUGR
Congenital anomalies Head to toe examination for malformations
Birth trauma Signs of trauma; cephalohematoma
, Common signs Cyanosis, jaundice, pallor, bleed, pustules, edema, depressed fontanel
,~pecial signs Caput; eye discharge; umbilical stump; discharge or redness; jitteriness; eye discharge; oral thrush;
development peculiarities (toxic erythema, Epstein pearls, breast engorgement, vaginal bleeding,
capillary hemangioma, mongolian spot)
Feeding Observe feeding on breast (check positioning and attachment)
Reflexes Moro, grasp, rooting
Systemic examination.
Chest Shape; respiratory rate; retractions; air entry; adventitious sounds
Cardiovascular system Apical impulse, heart sounds, murmur
Abdomen · Distension, wall edema, tenderness, palpable liver/spleen/kidneys, any other lump, ascites, hernial
sites, gonads, genitalia
Musculoskeletal system Deformities; tests for developmental dysplasia of hip; club foot
Central nervous system State of consciousness; vision, pupils, eye movements; facial sensation; hearing; sucking and
swallowing; muscle tone and posture; power; tendon reflexes ·
and plethora should be made. One should also look at the the apex of the baby's axilla by holding the thermometer.
spontaneous movements shown by the baby. · The finding of hypothermia (temperature of less than
36.5°C) in neonate has very important connotations.
Vital Signs . Neonates have a normal respiratory rate of 40-60 breaths/
In a sick baby, assessment of vital paramete~s takes priori~ minute. The HR is faster in preterm babies compared to
over all other examination. Temperature is measured m term babies. The normal HR range is 110-160 beats per
- 138
Fig. 9.12: Salient difference in physical characteristics of preterm and term neonates: (a) Well-curved pinna, cartilage reaching
up to periphery; (bl Flot and soft pinna, cartilage not reaching up to periphery; (c) Well-pigmented and pendulous scrotal socs,
with fully descended testes; (dl Light pigmentation and not yet descended testes; (el Deep transverse creases on the soles; (fl Faint
marks on the sole, no deep creases; (g) Well-formed breast bud (>5 mm); (hl Poorly developed breast bud; (I) Silky hair. where
indMdual strands con be mode out; Ul Fuzzy hair; (kl Labia mojoro covering clitoris and labia mlnora; and (I) Prominent labia
minora and clitoris
tightly shut while crying (Fig. 9.13). Nose is looked for its Subconjunctival hemorrhages are common after vaginal
size, shape, secretions, patency and flaring. The flaring of delivery and resolve spontaneously. The cornea should
the nostrils indicates an increase in respiratory efforts be clear. Pupils should be equal in size, reactive to light
and symmetrical.
regardless of the cause. Gross hearing is often assessed by looking for blink on
The alveolar ridge may have natal teeth or retention response to noise. More formal hearing screening for all
cysts (also called Epstein pearls) that disappear in a newborns is now recommended. Accessory auricles and
few weeks. It is very important to examine the palate for preauricular tags are common finding that inay be
deft. associated with renal anomalies.
- 140
Fig. 9.15: Sinus in lower back may signify underlying neural tube
defect
Neurological Examination
This consists of the assessment of the level of alertness
and examination of cranial nerves, motor and sensory
system and neonatal reflexes.
Cranial nerves: Neonates respond to cotton soaked in
peppermint by 32 weeks of gestation. By 26 weeks, the
infant consistently blinks in response to light and by term
a gestation, fixation and following (tested using fluffy red
yam ball) is well established.
By 28 weeks, the infant startles or blinks to loud
noise. Sucking and swallowing are important aspects
that should be examined as they give insight into the
proper functioning of the V, VII, IX, X and XII cranial
nerves.
The act of sucking requires the coordinated action of
breathing, sucking and swallowing. Suck-swallow
coordination so as to accept paladai feeding is present by
32 weeks. Suck-swallow and breathing coordination
occurs by 34 weeks when baby can breastfeed. However,
perfect coordination of suck-swallow and breathing
·1
.,,_:
I
Sources of Heat Loss
Response to hypotlrermia: Hypothermia -induced
Heat loss in a newborn occurs through four ways: peripheral vasoconstriction leads to increased metabolism
i. Radiation to surrounding environment not in direct with excess oxygen consumption and glucose utilization.
contact with baby Switch to anaerobic metabolism in hypothermia causes
ii. Convection to air flowing in surrounding metabolic acidosis (Fig. 9.18). The acidosis induces
iii. Conduction to substances in direct contact with baby pulmonary vasoconstriction and pulmonary hypertension
iv. Evaporation of amniotic fluid and moisture from baby's further worsening the hypoxernia. When body temperature
skin to atmosphere drops below 32°C, hemoglobin cannot release oxygen
Sources of Heat Production resulting il_l tissue hypoxia. The occurrence of hypoxemia,
bradycard1a, hypoglycemia and metabolic acidosis as a
When exposed to cold environment, the neonate tries to result of hypothermia contribute towards increased
generate heat by increasing physical activity (crying, mortality.
Hypothermia
Catecholamine release
Reduced surfactant
production
Displace bilirubin
bound to albumin Anaerobi~ metabolism, glycol .
Hyperbilirubinemia Hypoxem1a · ysrs
Metabolic acidosis
Management
Methods for temperature maintenance include skin-to.
skin contact, warm room, radiant warmers, incu?ators and
increasing ambient temperature by use of hot air blowers,
or a 200 watt bulb.
Severe Hypothermia
Fig. 9.20: (a) AA Incubator; and (b) Radiant warmer. Note that
Incubator Is covered with cloth to prevent excessive light or
• Remove all wet clothing and place baby in an incubator
noise for adequate comfort of the baby (air temperature 35-36°C), preheated radiant warmer
or thermostatically controlled heated mattress set at
37-38°C. Alternately, one may use a room heater.
temperature inside incubator by altering heater output • Once baby's temperature reaches 34°C, the rewarming
based on baby's temperature and thereby maintains the process should be slowed down.
temperature of baby in the normal range.
• Temperature is measured every hour for 3 hours. If rise
A radiant warmer is an open system (as compared to
of temperature has been by 0.S°C per hour then heating
incubator which is a closed cabinet) and the neonate lies
on a crib. There is overhead radiant warmer that ~ cons~dered adequate and temperature ~easureroent
modulates its heater output based on baby's temperature ~ con~ued 2 hourly until normal body temperature
is attained and thereafter 3 hourly for 12 hours. If rise
sensed by a skin probe. .
of temperature is not adequate one should check the
Radiant warmers and incubators should be used m the heating technique. '
servo-control mode with the abdominal skin temperature
maintained at 36.5°C to 37°C. • Provide oxygen, empirical antibiotics, saline bolus if
shock, IV dextrose and vitamin K. Monitor vitals.
Signs and Symptoms
Suggested Reading
Pe~ipheral vasoconstriction results in ac~ocyanos~s, ~ool
extremities and delayed peripheral capillary refill t~e • Guidelines for perinatal care Second Ed' ti A . AcadeJllY
. t n· cs an d American
o f P e d 1a · C i on, mencan
. . all
d
(CRT). The baby becomes restless and the~ lethargi.c. Gynecologists, 1998 ° 11ege of Obstetnc1ans
Chronic or recurrent episodes of hypothenrua. result m • Thermal protection of the n b WJJOI
poor weight gain. Cardiovascular manifestations may FHW /MSM/97.2 ew om: A practical guide.
•
Newborn Infants 1145 -
BREASTFEEDING factor in breast milk enhances maturation of the intestinal
Breast milk is an idea.I food for neonates. It is the best gift cells and reduces the risk of allergy in later life. Enzymes
that a mother can give to her baby. It contains all the like lipases increase the digestion of fats in the milk.
nutrients ~or nor~al growth and development of a baby Protectio11 ngainst otl1er il/11ess: Breastfed babies have a
from t~1e time of birth to the first 6 months of life. Ensuring lower risk of allergy, ear infections and orthodontic
exclusive breastfeeding for 6 months has a potential to problems. They have a lower risk of diabetes, heart disease
reduc.e u~der-5 m_o rtality rate by 13%, by far the most and lymphoma in later life.
effective mtervenhon that is known to reduce newb Mental growt/1: Babies who are breastfed are better
and child deaths. om
bonded to their mothers. Studies have shown that babies
To accrue t~e maximum benefits, the breastfeeding who were breastfed had a higher IQ than those babies
must be :xclus1ve (o_nly ?reast milk; nothing other than who were given other forms of milk.
breast milk except vitamin drops, if indicated), initiated
within an hour of birth and continued through first Benefits to motlier: Breastfeeding soon after birth helps
6 months after birth. uterine involution, reducing chances of postpartum
hemorrhage. It provides protection against pregnancy due
Benefits of Breast Milk to lactational ameno rrhea. If the mother has been
exclusively breastfeeding her baby and has not resumed
Nutritional superiority: Breast milk contains all the menses, then there is no need for any other contraception
nutrients a baby needs for normal growth and during initial 6 months after delivery.
development, in an optimum proportion and in a form Breastfeeding is most convenient and time saving. It
that is easily digested and absorbed. reduces the risk of cancer of breast and ovary. Breast-
Carboliydrates: Lactose is in a high concentration (6-7 g/ dL) feeding is the most effective way of shedding extra weight
in breast milk. The galactose is necessary for formation of that mother has gained during pregnancy.
galactocerebrosides. Lactose helps in absorption of
calcium and enhances the growth of lactobacilli, the good Breast Anatomy
bacteria, in the intestine. The breast is made up of glandular tissue, supporting
Proteins: The protein content of breast milk is low tissue and fat (Fig. 9.21). The glandular tissue consists of
(0.9-1.1 g/dL) compared to animal milk. Most of the small clusters of sac-like spaces which produce milk. Each
protein is in form of lactalbumin and lactoglobulin (60%), sac is lined by network of myoepithelial cells that propel
which is easily digested. Human milk contains amino the milk into lactiferous ducts towards nipple. Before
acids like taurine and cysteine which are necessary for reaching the nipple, the ducts widen to form lactiferous
neuro-transmission and neuromodulation. These are sinuses which store milk. The lactiferous sinuses lie
lacking in cow milk and formula. beneath the junction of areola and rest of breast.
The areola and nipples are extremely sensitive as they
Fats: Breast milk is rich in polyunsaturated fatty acids, are supplied by a rich network of nerve endings. On the
necessary for the myelination of the nervous system. It areola, there are small swellings of glands which produce
also contains omega 2 and omega 6 (very long chain) fatty
acids, which are important for the formation of prosta-
glandins and cholesterol. Oxytocin makes
Muscle cells { them contract
Vitamins and minerals: The quantity and bioavailability
of vitamins and minerals is sufficient to the needs of the Milk secreting Prolactin makes
cells { them secrete milk
baby in the first 6 months of life.
Water and electrolytes: Breast milk has a water content Ducts
of 88% and hence a breastfed baby does not require any Lactiferous {Milk collects
additional water in the first few months of life even during here
summer months. ..
lrnnumological superiorittj: Breast milk contains a number
of protective factors which include immunoglobulin-
rnainly secretory IgA, macrophages, lymphocytes,
lactoferrin, lysozyme, bifidus factor and interferon among
0
~hers. A breastfed baby is 14 times less likely to die of
diarrhea and almost four times less likely to die of
respiratory infection.
Supporting tissue Alveoli
~ther benefits: Breast milk contains a number of growth and fat
actor, enzymes and hormones. The epidermal growth Fig. 9.21: Anatomy of breast
- 146
br
- 148 Essential Pedlat~~-----------~
~
~ ~ Insert piston
.-.L------~~~=~
....
from cut end
Mother genUy
pulls the piston
•
Expressed Breast Milk (EBM)
If a mother is not in a position to feed her baby (e.g. ill
mother, preterm baby, working mother, etc.), she should Step 4
express her milk in a clean wide-mouthed container and
this milk should be fed to her baby. EBM can be stored at Fig. 9.27: Four steps of breast m ilk expression. Step l: Massage
room temperature for 6-8 hours, in a refrigerator for the breasts gently toward the nipples; Step 2: Place the thumb
24 hours and a freezer at -20°C for 3 months. and Index finger opposite each other just outside the dark circle
around the nipple; Step 3: Press back toward the chest, then
Method of Milk Expression gently squeeze to release milk; Step 4: Repeat step 3 In different
positions around the areola
Ask the mother to wash her hands thoroughly with soap
and water before she expresses. She should make herself gestation) or due to intrauterine growth restriction (IUGR)
comfortable. Gently massage the breast (Fig. 9.27). Hold or both.
the container under her nipple and areola. Place her thumb IUGR is similar to malnutrition and may be present in
on top of the breast at least 4 cm from the tip of the nipple both term and preterm infants. Neonates affected by IUGR
and the first finger on the undersurface of the breast are usually undernourished and have loose skin folds on
opposite the thumb. Compress and release the breast the face and in the gluteal region (Fig. 9.28), absence of
tissue between her fingers and thumb a few times. subcutaneous fat and peeling of skin. Problems faced by
If the milk does not appear, she should reposition her a preterm and IUGR neonate are different, although the
thumb and finger closer to the nipple and compress and management principles are common to both (Table 9.8).
release the breast as before. Compress and release all the IUGR results when the fetus does not grow as per the
way around the breast. Express milk from both breasts. normal fetal growth trajectory. Fetal growth restriction
To maintain adequate lactation, mother should express results from one or more adverse factors that affect the
milk at least 8 to 10 times in 24 hours. normal growth pattern of the fetuses. There are two types
of IUGR babies:
CARE OF LOW BIRTH WEIGHT BABIES • Symmetric IUGR: When insult on the ~etal growth occurs
Low birth weight (LBW; birth weight less than 2500 g) early. The size of the head, body weight and length are
babies have higher morbidity and mortality. LBW results equally reduced. Causes inclu.d e g.enetic and
from either preterm birth (before 37 completed weeks of chromosomal disorders or TORCH infections.
- 150
Resuscitation
Problems
• Compromised intrauterine .environment with high~
chances of perinatal asph yXIa .
• Preterm babies have immature lungs that may be more
difficult to ventilate.
• Immature blood vessels in the brain are prone to
hemorrhage.
• Thin skin and a large surface area, which contribute to
rapid heat loss.
Fig. 9.28: Baby with intrauterine growth retardation show;ng • Increased risk of hypovolemic shock caused by small
many loose folds of skin blood volume.
Management
r . . -·-- ·- -· • Adequate preparation for higher need for resuscitation
Table 9.8: Major problems in preterm bab~s and those with
I intrauterine growth ~etardation (IUGR) 1 • Gentle resuscitation using small bags for positive
Preterm babies pressure ventilation, use of CPAP
Hypothermia • Take extra care to avoid hypothermia
Perinatal asphyxia Temperature Control
Respiratory (hyaline membrane disease, pulmonary hemorr-
Problems
hage, pneumothorax, bronchopulmonary dysplasia, pneumonia)
Bacterial sepsis • Higher surface area to body weight ratio
Apnea of prematurity • Low glycogen stores
Metabolic (hypoglycemia, hypocalcemia)
• Low subcutaneous fat
Hematologic (anemia, hyperbilirubinemia) Management
Feeding problems and poor weight gain • Freq~ent mo~toring and educating parents
• Special attention to maintenance of the warm chain
Babies with IUGR
• Kangaroo mother care
Perinatal asphyxia
Meconium aspiration Fluids and Feeding
Hypothermia
These have been discussed under the section on feeding.
Hypoglycemia
Feed intolerance Infection
Polycythemia Problems
Poor weight gain • Immature defenses
• Greater. probability of invasive interventions like
mecharucal ventilation, umbill'ca1vessel cathetenzahon.
. ·
• Asymmetric JUGR: The insult on the fetal growth occurs
during late gestation producing a brain sparing effect. Management
Head circumference is relatively preserved compared • Strict adherence to asepsis hand h .
• M' · , yg1ene
to length and weight. Causes include placental rmmal handling of babies
insufficiency, pregnancy-induced hypertension or • High index of s · · f
antibiotics usp1c1on of sepsis, rationale use o
maternal medical diseases.
• Decreasing ex ·h
Small for gestational age (SCA): It is a statistical definition . posure to adults/other children wJt
commurucable dise .
and denotes weight of infant being less than 2 standard ases particularly respiratory.
deviation or less than the 10th percentile of the population Metabollc Derangements
norms (plotted on intrauterine growth chart). For the Problems
practical purpose, SGA and IUGR are considered • Low hepatic glyco eSS
synonymous. places these in£ gen ~tores With rapid depletion ins~
ants at increased risk of hypoglycenua·
-
• Immature glucose
premature
. homeosta t'ic mechanisms
b abies can also lead t d
.
.
Newborn Infants
. .
.
m • Improves breastfeeding rate
I 1s1 •
Birth weight
/' ..
e r'
Fig. 9.30: (a) Mother and (b) Father practicing KMC In front open gown and shawl·
KMC using AllMS KMC Jacket. (eJ A mother providing KMC to her twin babies On ·~~ AllMS KMC Jacket; (d) Mother pertorrnl~
0
(fl KMC being practiced In a ventilated baby · e Y Is receiving oxygen by open tube;
Newborn Infants I 1s3
procedure
l(a11garoo positio11i11g: The baby should be placed between
the mother's breasts in an upright position (Fig. 9.31). The
head should be turned to one side and in a slightly
extended position. This slightly extended head position
keeps the airway open and allows eye-to-eye contact
beh·veen the mother and her baby. The hips should be
flexed and abducted in a ' frog' position; the arms should
also be flexed. Baby's abdomen should be at the level of
the mother's epigastrium. Mother's breathing stimulates
the baby, thus reducing the occurrence of apnea. Support
the baby's bottom with a sling or binder.
Mo11itori11g: Babies receiving KMC should be monitored
carefully, especially during the initial stages. The baby's
neck position is neither too flexed nor too extended,
breathing is regular, color is pink and baby is maintaining
temperature.
Feeding: The mother should be explained how to
breastfeed while the baby is in KMC position. Holding
the baby near the breast stimulates milk production. She
may express milk while the baby is still in KMC position.
The baby could be fed with paladai, spoon or tube,
depending on the condition of the baby.
Privacy: The staff must respect mother's sensitivities in this
regard and ensure culturally acceptable privacy standards
in the nursery and the wards where KMC is practiced.
Duration: Skin-to-skin contact should start gradually in
the nursery, with a smooth transition from conventional
care to continuous KMC (Fig. 9.32). Sessions that last less
than one hour should be avoided because frequent
handling may be stressful for the baby. The length of skin-
to-skin contact should be gradually increased up to
24 hours a day, interrupted only for changing diapers.
Fig. 9.32: Kangaroo mother care being provided to extremely
low birth weight babies
When the baby does not require intensive care, she should
be transferred to the postnatal ward where KMC should
be continued.
The mother can sleep with baby in KMC position in
reclined or semi.recumbent position about 30° from
horizontal. This can be done with an adjustable bed or
with pillows on an ordinary bed. A comfortable chair
with an adjustable back may be used for resting during
the day.
Initiate breastfeeding
Observe if:
Positioning and attachment are good
Able to suck effectively and long enough
(about 10-15 min) 32-34 weeks
Yes No
j Breastfeeding j Start feeds by spoon or paladai
I
Observe if:
Accepting well without spilling/coughing
Able to accept adequate amount 28-31 weeks
Yes No
j Spoon or pa/adai feeding J Start feeds by orogastric or nasogastric tube
Observe if:
~
Vomiting or abdominal distension occurs
<
k
8 wees
No Yes
If accepting well
I
once the mother is confident
Fig. 9.35: Progression of oral feeding In preterm LBW infants. Term and near-term sick Infants started on intravenous (IV) fluids can
be Initiated on breastfeeding once they are hemodynamlcally stable
milk can be stored for about 6 hours at room temperature Infants wlio are fed by spoon!paladai or by iutragastric
and for 24 hours in domestic refrigerator (2° to 8°C). htbe: The daily fluid requirements of neonates have been
The steps of breast milk expression are given in Fig. 9.27. discussed in the section of fluids and electrolytes. VLBW
infants (<1500 g) need about 80 mL/kg fluids on the first
Sick mothers/contraindication to breastfeeding: In these day of life. It needs to increased by 10-15 mL/kg/day to
rare circumstances, the options available are: a maximum of 160 rnL/kg/ day by the end of the first week
i. Formula feeds: of life. LBW infants >1500 g are usually given about
a. Preterm formula in VLBW infants, and 60 rnL/kg fluids on the first day of life and fluid intake is
b. Term formula in infants weighing 1500 g or more increased by about 15-20 mL/kg/ day to a maximum of
at birth 160 ml/kg/ day by the end of the first week of life. The
ii. Animal milk, e.g. undiluted cow milk volume for an individual feed can be determined by diving
Once the mother's condition becomes stable (or the total fluid to be given divided by number of feeds planned
contraindication to breastfeeding no longer exists), these in 24 hours.
infants should be started on exclusive breastfeeding.
Nutritional Supplementation
How Much to Feed? Birth w eig11t of 1500-2499 g: These infants are more likely
to be born at term or near term gestation (>34 weeks). They
Infants who are breastfed: Infants who are able to suckle need vitamin D and iron (Table 9.11).
effectively at the breast should be breastfed on demand.
Small babies (<2000 g) may not be relied on demand Birth w eight <1500 g: Those infants who are usually born
before 32-34 weeks gestation have inadequate body stores
feeding and be fed every 2-3 hours.
II 158 Essential Pediatrics
- . ~
.. ---12· causes of inadequate weight gain . . .,_l
of most of the nutrients. Since EBM has inadequate , Table 9. ·
I .
amounts of protein, energy, calcium, phosphorus, trace Inadequate Intake
elements (iron, zinc) and vitamins D, E and K, it is often
Breastfed infants
not able to meet the daily requirement of these infants. Incorrect feeding method (Improper positioning or
Hence, these infants need multinutrient supplementation
attachment)* · h ·
till they reach term gestation (40 weeks, i.e. until the eastfeeding, not feeding in t e night hours•
Less frequen t br
expected date of delivery) . These nutrients can be
Infants on spoon or pa/adal feeds . .
provided by fortification of expressed breast milk with
Incorrect method of feeding* (e.g. ~xcess sp1lhng)
human milk fortifiers (HMF). Fortification increases the
nutrient content of the milk without compromising its Incorrect measurement or calculation
other beneficial effects. As HMF does not provide Infrequent feeding* .
adequate iron, the same has to be given separately in form Not fortifying the milk in VLBW infants
of drops. Fortification or supplementation of minerals and
vitamins should be continued only till term gestation (40 Increased demands
weeks) in VLBW infants. After 40 weeks, only vitamin D Hypothermia or cold stress*
and iron needs to be supplemented (similar to infants with , Chronic illnesses, bronchopulmonary dysplasia
birth weights of >1500 g). Medications such as corticosteroids
*Common causes
Growth Monitoring of LBW Infants
Regular growth monitoring helps in assessing the iv. Proper demonstration of the correct method of
nutritional status and adequacy of feeding in LBW infants; expression of milk and paladai feeding: It is important
it also identifies those infants with inadequate weight gain. to observe how the mother gives paladai feeds; the
All LBW infants should be weighed daily until the time technique and amount of spillage should be noted. This
of discharge. Length and head circumference should be should be followed by a practical demonstration of the
recorded weekly. proper procedure.
Both term and preterm LBW infants tend to lose weight v. Ensuring optimum thermal protection
-
- - 160
. . f kin integrity with needle pricks and use f
followed by application of 0.5% gentian violet four d1srupt10n o s o
times a day till redness subsides would take care. intravenous fluids.
• Severe infection: When area of redness extends beyond
Cl/n/cal Features
1 cm of surrounding tissue or there are signs of sepsis
local therapy plus systemic antibiotic should be started NNS often manifests with ~ag~e and ill-de~e.d symptotns
uires high index of susp1c1on for early
as in management of septicemia. and t herefore, req .f. ·f
. ' . A early but non-spec1 1c mam estation is
Oral thmsh: White patchy lesions on the oral mucosa and diagn~s1s'. tnhe established feeding behavior. The baby
tongue can occur in healthy newborns. True oral thrush alterat10n in . fu '
who had been active and sucking norma 11y~ re ses to suck
lesions are difficult to wipe off and leave hemorrhagic es lethargic, or unresponsive. Poor cry
points when removed. Local nystatin or clotrimazole an d b ecom . .. d '
application four times a day after feed is recommended. h ypo therm ' abdominal distens10n,
ia
·f
vomiting an apneic
· n · h
spells are other common mam estat10~s . iarr ea is
Co11j11nctivitis: Infection should be differentiated from on. Fast breathing, chest retractions and grunt
uncomm f . .. d
sticky eyes and blocked nasolacrimal duct. Sticky eyes · d " t pneumonia. Most cases o merung1tis o not have
in 1ca e kin . d
generally manifests as mucoid discharge without any signs any distinct clinical picture per se, ma g it man atory
of inflammation and requires cleaning with saline. to suspect meningitis in all cases suspected of sepsis.
Conjunctivitis manifests as purulent discharge and signs Shock, bleeding, sclerema and renal failure are indicators
of inflammation and requires local instilla tion of of overwhelming sepsis. ·
antibiotics. Gonococcal conjunctivtis can result in Diagnosis of sepsis is fraught with poor specificity._ A
blindness and requires timely systemic antibiotics therapy. host of conditions like hypothermia, hypertherm1a,
hypoglycemia, hypoxia, late ~etabolic .a~ido~is,
Systemic Infections (Neonatal Sepsis) congestive heart failure and eve~ srmple conditio~ !ll<e
When pathogenic organisms gain access into the blood- nasal block may mimic sepsis. A careful chmcal
stream, it can result into neonatal sepsis, which may be examination and relevant investigations are necessary to
generalized and/ or localized to the lungs (pneumonia), differentiate these conditions from NNS and avoid
the meninges (meningitis) or bones and joints unnecessary antibiotics therapy. Babies who are clinically
(osteomyelitis/ arthritis). Systemic bacterial infections are stable can be ob served, without admission and
known by the generic term neonatal sepsis (NNS), which intravenous antibodies, while providing good supportive
incorporates generalized sepsis, pneumonia, meningitis care (Fig. 9.36).
and bone-joint infections.
Investigations
Etiology No investigation is required to start treatment in a sick
Escherichia coli, Staphylococcus aureus and Klebsiella sp. are baby who has high probability of sepsis (Fig. 9.36). Blood
the predominant organisms. Organisms like Acinetobacter, culture provides definitiv e diagnosis of NNS and should
Pseudomonas and coagulase negative staphylococci are be taken before starting antimicrobial therapy. After
also important pathogens in healthcare associa ted cleaning the skin (with alcohol, povidone iodine and again
infections. alcohol), a specimen of 0.5 to 1.0 mL of blood can be taken
in a small culture media bottle containing 5 to 10 mL of the
Early Versus Late Sepsis liquid broth.
Early-onset sepsis (EOS) (up to. 72 hours after .birth) A panel of tests (sepsis screen) consisting of total leukocyte
infections are cau sed by organisms prevalent m the count (TLC; <5000/mm3), absolute neutrophil count (ANC
3
maternal genital tract or in the delivery area. EOS occurs <1800/mm ), immature to total neutrophil ratio (I/T ratio;
in presence of p erinatal risk factors namely spontaneous more than 20%), CRP (more than 1 mg/dL) and micro-ESR
onset of preterm labor, prolonged rup~re of me~br~nes, (15 mm or more in the first hour) constitute a useful sepsis
foul smelling liquor, multiple per vaginal exammations, scre~n for clii:'~cal~y doubtful cases. Sepsis scree~ is
maternal fever, and difficult or prolonged labor. EOS considered positive, if two of these parameters are positive.
frequently manifests as pneumonia and less commonly Lumbar puncture should be p erformed in all cases
as septicemia or meningitis. . . ~uspe~ted of NNS except in asymptomatic babies being
Late-onset sepsis (LOS) (72 hours or later) infections mveshgated for maternal risk factors. Table 9.13 provides
are caused by the organisms thriving in t~e ext~rn~l gestation specific cut offs for values of various parameters
environment of the home or the hospital. The mfechon is in cerebrospinal fluid.
often transmitted through the hands of the care-provider.s. Treatment
The presentation is that of generalized sepsis, pneumorua
or meningitis. The predisposing factors inc!~de ~BW, !ack Ins~itution of prompt treatment is essential for ensuring
of breastfeeding, poor cord care, superficial mfechons optimum outcome ~f.~eonates with sepsis who often r~ach
(pyoderma, umbilical sep sis), aspiration of feeds and the health care facilities late and in a critical condition·
Newborn Infants 161 -
:~able·~.13:. Normal c·sF examination. fr1 neonates, mean (range) over 5-10 minutes, if perfusion is poor. Repeat the same
1-2 times over the next 30-45 minutes, if perfusion
I
Test · Term Preterm
Cells
continues to be poor. Dopamine and dobutamine may be
Leukocytes 7 (0-32) 9 (0-29) required to maintain normal perfusion.
. Polymorphonuclear cells 61% 57% • Insert intravenous line. If hypoglycemia is suspected,
infuse glucose (10%) 2 mL/kg stat. Do not use glucose
. Protein (mg/dl) 90 (20-170) 115 (65-150)
boluses routinely. Provide maintenance fluid,
Glucose (mg/dL) 52 (34-119) 50 (24-63) electrolytes and glucose (4-6 mg/kg/min). Add
potassium to IV fluids once normal flow of urine has
Supportive care and antibiotics are the two equally been documented.
important components of treatment. Antibiotics take at • Ensuring optimal nutrition is extremely helpful in sick
least 12 to 24 hours to show any effect, optimum suppor- babies. Enteral feeds should be initiated early, if there
tive care improves the outcomes in sick septic babies. is no abdominal distension and baby is hemo-
dynamically stable. Feed mother's milk.
Supportive care: Good supportive care requires meticulous
attention to various aspects: Specific care: Antimicrobial therapy constitutes the
• Provide warmth; ensure normal temperature (36.5°- mainstay of treatment of sepsis. In a seriously sick neonate
37.S0C). suspected of sepsis, appropriate antibiotics therapy should
• Start oxygen by hood or mask, if the baby is cyanosed be initiated without any delay after obtaining blood
or grunting. Provide bag and mask ventilation, if samples for culture.
~reathing is inadequate. Instilling normal saline drops Empiric tl1erapy wl1e11 etiologic agent is not k11ow11: The
tn nostrils may help clear the nasal block. empiric therapy ofNNS should cover the major causative
• Asses.s peripheral perfusion by palpating peripheral pulses, pathogens while awaiting reports of culture studies.
capillary refill time (normally <2-3 seconds) and skin color. Smee the antimicrobial spectrum and susceptibility
· Serial measurement of urine output is helpful for this profile is different in different settings, there cannot be a
Purpose. Infuse normal saline or Ringer lactate 10 mL/kg universal policy of empiric regimen. Antibiotics are often
• 162
('" -·
l
Clinical situation Septicemia and pneumonia Meningitis
Community acquired; resistant Ampicillin or penicillin and gentamicin Cefotaxime and gentamicin
strains unlikely (first line)
Hospital acquired or when there is Ampicillin or cloxacillin and amikacin Cefotaxime and amikacin
a low to moderate probability of (second line)
resistant strains
Hospital acquired sepsis or when Cefotaxime and amikacin Cefotaxime and amikacin
there is a high probability of (third line)
resistant strains ·
Therapy might be modified based on culture report
used in neonates on the slightest suspicion of sepsis outcomes. The reported mortality rates in neonatal sepsis
because of the grave and fulminant nature of neonatal in various studies from India ranges between 45 and 58%.
sepsis. But unbridled overuse of antibiotics is associated
Necrotlzing Enterocolitis
with the serious risk of emergence of resistant strains of
pathogens. Most newborn units in the country are facing Necrotizing enterocolitis (NEC) occurs among smaller
the problem of overwhelming antimicrobial resistance to premature infants, often those less than 32 weeks. The
practically all antibiotics. Rational use of antibiotics is, clinical picture mimics neonatal septicemia because of the
therefore, the responsibility of every physician. presence of abdominal distension, apnea, bradycardia,
Each treating unit should adopt a suitable policy. Based instability of temperature, cyanosis and lethargy.
on changes in the spectrum of etiologic agents and the Management
antibiotics sensitivity pattern, the choice of antibiotics
must be periodically reviewed and modified. Table 9.14 Oral feeding should be withheld. A nasogastric tube is
provides possible regimen of empiric antibiotics. inserted to relieve distension and to aspirate stomach
contents. Fluids and electrolytes in adequate quantities
Therapy after an etiologic agent is known: Antimicrobial
should be administered. Parenteral nutrition may be
ther~i:y.can be ma?e sp~cific once a positive culture and
Tabl~ 9.15: Essential crite_ria for pe;l~atal asphyxia - · • Table 9.16: Neurological patterns of hypoxic-tschemlc
·prolonged m~tabolic or mixed acidemla (pH <7 .O) on an encephalopathy
umbilical arterial blood sample Premature newborns
persistence of Apgar score of 0-3 for >5 minutes Selective subcortlcal neuronal necrosis
Neurolog_ic~I mani!estations, e.g. seizures, coma, hypotonia Periventrlcular leukomalacia
or hypoxic 1schem1c encephalopathy (HIE) in the immediate Focal and multifocal ischemlc necrosis
neonatal period
Periventricular hemorrhage or Infarction
Evidence of multiorgan dysfunction in the immediate neonatal
period Term newborns
Selective cortical neuronal necrosis
Neuropathology Status marmoratus of basal ganglia and thalamus
Parasagittal cerebral injury
These differ according to gestation (Table 9.16) and are of Focal and multifocal ischemic cerebral necrosis
the following main types:
Selective neuronal necrosis involves cerebral cortex, Hypoxia is an evolving process that starts at the onset of
the insult and continues after resuscitation and thereafter
hippocampus, basal ganglia, cerebellum and anterior horn
manifests in form of sequelae. Management thus depends
cells of spinal cord. Seen predominantly in term infants
on which point in this evolution it is detected; with the
and depending on site, this manifests clinically as
preventive approach beginning in the prenatal period and
diminished consciousness, seizures and abnormalities of
then continuing in the form of a long follow-up much after
feeding, breathing, etc. Parasagittal area is a watershed the stabilization of the initial condition.
area for
many arteries and is vulnerable to ischemia
A wide-spectrum of clinical manifestations is seen
D
resulting in proximal limb weakness (upper >lower) that depending on the severity of injury. These manifestations
later may develop into spastic quadriparesis. Status change over time and are clinically noted in babies of
marmoratus is a variant of selective neuronal necrosis gestational age more than 36 weeks by classification on
involving basal ganglia and thalamus, having long-term
sequelae such as choreoathetosis, spastic quadriparesis
the basis of Levene stages of HIE (Table 9.17). I
HIE staging helps predict evolution of the disease and
and retardation. long-term outcome. Babies with stage 1 have uniformly
Preterm good prognosis. Adverse neurological outcomes are
present in 20% of babies with stage 2 HIE. In stage 3 HIE,
Selective neuronal necrosis is rare in preterms; half of the neonates die and remaining half tend to have
diencephalic neuronal necrosis restricted to thalamus and poor neuro-development outcomes.
brainstem w ith or without hypothalamus and lateral
geniculate body is seen. Hypoxia and acidosis fo~o~ed Post-Resuscitation Management of an
by hyperoxia demonstrates a unique pattern of m1ury Asphyxiated Baby (Fig. 9.37)
involving pontine nucleus and s ubiculum of the i. Temperature: Maintain normal temperature of the baby
hippocampus. and avoid hyperthermia. In resourceful setting,
Periventricular leukomalacia (PVL) results from moderate induced hypothermia (core temperature of
hYPoxic-ischemic insult leading to coagulative ne~rosis 33° to 34°C) reduces the death or severe neuro-
and infarction of periventricular white matter that is the developmental handicap. However, the efficacy and
Watershed area between various ar teries . Long-term safety of therapeutic hypothermia has not been proved
sequelae of PVL include spastic diplegia and quadriplegia in resource restricted setting (in absence of intensive
(lower limbs >upper limbs) and visual impairment. care).
Moderate Severe
-·r·'··---· ....._ . .,,_
I'
-~
.- .
....
,
· ' ..
Feature
' Consciousness Irritability Lethargy Comatose
~i :, :, Tone Hypotonia Marked hypotonia Severe hypotonia
,!. Seizures No Yes Prolonged
: ~- · Suckingirespiration . . Poor suck Unable to suck . Unable to sustain spontaneous respiration .
~Odlfled from: Levene Ml.The asphyxiated newborn infant. In: Levene Ml, Lilford RJ, ed. Fetal and Neonatal Neurology and Neurosurgery. Churchill
Livingstone, Edinburgh 1995;405-26 · .
- 164 ~~~~~~~~~~~~~~E!ss~e~n~t~la~l~P!e~d~la~tr~lc~s~~~~~~~~~~~~-----~
..
Need for positive pressure ventllatlon for :?30 seconds,
chest compression or adrenaline
Apgar <7 at 5 minutes
ii. Oxygen: Both hypoxia and hyperoxia can damage if neurological examination is normal and baby is feeding
neurons. Oxygen saturations are maintained between well on breast.
90 to 95%. C02 concentration in ventilated babies
should be maintained between 40 and 50 mm Hg as Prognosis
hypocarbia as well as hypercarbia are detrimental to The following features predict a poor outcome:
brain. • Lack of spontaneous respiratory effort within 20-30
iii. Perfusion: Cerebral perfusion in asphyxiated babies is minutes of birth is associated with almost uniform
in 'pressure passive' state means there is loss of auto- mortality
regulation and blood supply to the brain is entirely • HIE stage3
dependant on BP; it decreases when BP falls and • Abnormal neurological findings pe~sisting beyond the
increases when BP rises. Therefore, to maintain normal first 7-10 days of life
perfusion pressure, a systemic mean arterial pressure • Oliguria (<1 mL/kg/ day) during the first 36 hours
of 45-50 mm Hg (term), 35-40 (1-2 kg weight) and . Thus a~ th~se babies should have regular follow-up
30- 35 mm Hg (<1 kg weight) is required. Judicious with momtonng of neurodevelopmental milestones to
use of fluid boluses and use of vasopressors help detect any deficits early and to intervene effectively.
maintain BP.
iv. Glucose: Levels between 75 and 100 mg/ dL are recom- Suggested Reading
mended. Hyperglycemia enhances cerebral edema and
compromises perfusion, while hypoglycemia poten- • Agarwal R, Jain A, Deorari AK, Paul VK. Post-resuscitation
:~nagement of asphyxiated neonates. Indian J Ped.iatr 2008;75:175-
tiates excitotoxic damage. Hypoglycemia is commonly
seen in asphyxiated infants and the infant must be
regularly monitored. RESPIRATORY DISTRESS
v. Metabolic profile: Hypocakemia and electrolyte
disturbances should be regularly looked for until Resp.iratory distress in the neonate is a common problem
stabilization of baby and corrected as indicated. and
d" it can . be .a seriou s neonatal emergency. Respiratory
.
vi. Seizures: 20-50% of infants with HIE develop seizures i~tress is defmed as presence of tachypnea (RR >60I min)
during day 1 or 2. Seizures are commonly subtle or with lower ches.t retractions, gruntin and c anosis. It call
focal or multifocal. Metabolic disturbances such as be due to respiratory (Table 9 lB) g d Y . tory
causes (Tab! 9 19 ) · an non-resprra
hypoglycemia, hypocalcemia and hyponatremia must treatment is e:se~tial ·t E~rly recognition and prompt
be ruled out. Seizures should be treated with anti- 0
improve the outcomes.
epileptic drugs (AEDs) such as phenobarbitone and
phenytoin. The seizures may be intractable initially but Approach
usually tend to burn out by 48 hours. Subtle seizures Respiratory distress in a neon . by
lasting for brief duration need not be treated. the presence of var in . ate can be recognized
Once the baby is seizure-free for 3-4 days, AEDs are >60 /min) chest retry ti? combinations of tachypnea (~
, ac ons gr tin . as1
stopped in the same order as they were started, except and cyanosis. The gestati~n un g, flanng of a1a~ n of
phenobarbitone. Phenobarbitone is stopped at discharge, distress and presence of '.age at onset, seventy
associated clinical features help
I 16s -
, Table 9.19: Non-p~imo~ary -~uses o~ r~pid breathing . · : Respiratory Distress Syndrome (RDS)
Cardiac ~ongestive heart failure; congenital he~rt · RDS is common in preterrn babies less than 34 weeks of
disease
gestation. The overall incidence is 10-15% but can be as
Metabolic Hypothermia, hypoglycemia, metabolic high as 80% in neonates <28 weeks. In addition to
acidosis prematurity, asphyxia, acidosis, maternal diabetes and
Central nervous Asphyxia, cerebral edema, hemorrhage cesarean section can increase the risk of RDS.
system
Chest wall Asphyxiating thoracic dystrophy,
Etiopathogenes/s
Werdnig-Hoffman disease In RDS, the basic abnormality is surfactant deficiency.
Surfactant is a lipoprotein-containing phospholipids like
in arriving at diagnosis. It should be noted that chest phosphatidylcholine and phosphatidylglycerol and
retractions are mild or absent in respiratory distress due proteins. Surfactant is produced by type II alveolar cells
to non-respiratory causes.
Respiratory causes: Conditions listed in Tables 9.18 and
9.19 can occur both in preterm and term babies. However,
if a preterm baby has respiratory distress within the first
of lungs and helps reduce surface tension in the alveoli.
In the absence of surfactant, surface tension increases and
alveoli tend to collapse during expiration. During
inspiration, more negative pressure is needed to keep
alveoli patent. There is inadequate oxygenation and
I
few hours of life, the most likely cause is respiratory increased work of breathing. Hypoxemia and acidosis
distress syndrome (RDS). Similarly, if a term baby born result in pulmonary vasoconstriction and right to left
to a mother with meconium-stained liquor develops shunting across the foramen ovale. This worsens the
respiratory distress within the first 24 hours, the most hypoxemia and the neonate eventually goes into
likely cause is meconium aspiration syndrome (MAS). A respiratory failure. Ischemic damage to the alveoli causes
term baby with uncomplicated birth developing transudation of proteins into the alveoli that forms
tachypnea in the first few hours of birth is likely to have hyaline membrane. Surfactant production starts around
transient tachypnea of newborn. Presence of suprastemal 20 weeks of life and peaks at 35 weeks gestation.
recessions with or without stridor indicates upper airway Therefore, any neonate less than 35 weeks is prone to
obstruction. develop RDS.
I Contraindications
• Frank chorioamnionitis as suggested by (1) history of fever
and lower abdominal pain, (2) on examination: foul smelling
vaginal discharge, tachychardia and uterine tenderness and
(3) fetal tachycardia
• Maternal diabetes, pre-eclampsia and hypertension are NOT
contraindications
· Regimen
• Injection Dexamethasone 6 mg intramuscularly. A total of
Fig. 9.39: Continuous positive airway pressure being provided 4 doses at interval of 12 hours. Appropriate preparation of
to a preterm baby betamethasone can also be given but is not available in India.
• ACS exerts maximal benefits when delivery happens
24 ~ours atte.r the. last dose and up to 7 days thereafter.
(Fig. 9.39). This is an excellent modality of respiratory Partial effect is evident within a few hours before birth as
support which minimizes lung injury and other compli- well as after 7 days.
cations such as air leak and sepsis. Preterm babies • Oral preparations of ACS are not useful.
developing severe RDS often require mechanical • Repeated courses are not indicated
ventilation. Preterm babies are at risk of lung injury by
Benefits
excessive pressure and high oxygen. High saturations of
Reduction in
oxygen (above 95%) can produce retinopathy of pre-
• Respiratory distress syndrome (RDS)
maturity (ROP) which can blind the infant.
• lntraventricular hemorrhage (IVH)
Since surfactant deficiency is the basis of RDS, • Necrotizing enterocolitis (NEC)
exogenous surfactant is recommended as the treatment • Neonatal mortality
of choice for moderate to severe RDS.
• Other ~e~effitst:· Reduced Incidence of PDA, reduction in
systemic 1n ec ions, decreased need for . t rt
Prevention of RDS f resp1ra ory suppo
~ntd, t~ere ore, ~d~c~d length of hospital stay, low rate of
Administration of antenatal steroids to mothers in preterm ' m ens1ve ~are a r:n1ss1ons and finally reduced cost of care.
labor (<35 weeks) has been a major breakthrough in Not associated with any significant sho t t · 1 or
. r - erm materna
management of preterm infants. Antenatal steroids fetal adverse effects. No increased risk of m t
·
· f t'on
a erna1m ec 1 •
167 -
Surgical Problems
Tracheoesophageal fistula (TEF) should ?e sus~ected in
any neonate with excessive frothing. Diagnosis can be
~Onfirmed by a plain X-ray with a red ru~ber cath~ter (not
~ant feeding tube, it is soft and gets coiled up) mserted
in stomach. Presence of gastric bubble suggests
concomitant TEF. . ·
·Diaphragmatic hernia should be s~spected many Ag. 9.41: Tension pneumothorax on right side displacing the
neonates who has severe respiratory distress and has a mediastlnum and pushing down the diaphragm
II 1ss
Apnea of prematurity occurs in preterm neonates Breastfeeding Jaundice
between the second to fifth days of life and is because of Exclusively breastfed infants have a differe~t .P~ttern of
the immaturity of the developing brain. Central apnea can physiological jaundice as compar~d to artificially fed
also occ':1r because of pathological causes like sepsis, babies. Jaundice in breastfed babies usually appears
metabolic problems (hypoglycemia, hypocalcemia), between 24 and 72 hours of age, peaks.by S-l 5 da.ys ofUfe
temperature instability, respiratory distress, anemia and
polycythernia. Obstructive apnea can occur because of block
.
an d d 1sappears by the third week of life. . . . Of alJ
'ld One-third
1
breastfed babies are detected to have mi . c ~cal Jaundice
to the airway by secretion or improper neck positioning. in the third week of life, which mayp~rsist into the 2nd to
Treatment is supportive and involves correction of 3rd month of life in a few babies. nus increased frequency
underlying cause. Apnea of prematurity is treated with of jaundice in breastfe~ babies is not ~elated to
arninophylline or caffeine. Prognosis is good in apnea of characteristics of breast milk but rather to inadequate
prematurity. In other cases, it depends on the underlying breastfeeding (breastfeeding jaundice)·. Eru:uring ?Ptimum
cause.
breastfeeding would help decrease this kind of Jaundice.
JAUNDICE Breast Milk Jaundice
Jaundice is an important problem in the first week of life. Approximately 2-4% of exclusively breastfed term babies
High bilirubin levels may be toxic to the developing have jaundice in excess of 10 mg/ dL ~eyon? 3rd-4th
central nervous system and may cause neurological weeks of life. These babies should be investigated for
impairment even in term newborns. Nearly 60% of term prolonged jaundice. A diagnosis of breast milk jaundice
newborns become visibly jaundiced in the first week of should be considered, if this is unconjugated (not staining
life. In most cases, it is benign and no intervention is nappies); and other causes for prolongation such as
required. Approximately, 5-10% of them have clinically inadequate feeding, continuing hemolysis, extravasated
significant jaundice requiring use of phototherapy or other blood, G6PD deficiency and hypothyroidism have been
therapeutic options. ruled out. Mothers should be advised to continue
breastfeeding at frequent intervals and TSB levels usually
Physiological Versus Pathological Jaundice decline over a period of time. Some babies may require
I
Physiological jaundice represents physiological phototherapy. Breastfeeding should not be stopped either
immaturity of the neonates to handle increased bilirubin for diagnosis or treatment of breast milk jaundice.
production. Visible jaundice usually appears between
Clinical Estimation
24-72 hours of age. Total serum bilirubin (TSB) level
usually peaks by 3 days of age and then falls in term ~r~gin.ally described by Kramer, dermal staining of
neonates. TSB levels are below the designated cut-offs for ~1hru~m may be used as a clinical guide to the level of
phototherapy. It does not require any treatment. Jaundice. Dermal staining in newborn progresses in a
Pathological jaundice is referred to as an elevation of cephalocaudal direction. The newborn should be
TSB levels to the extent where treatment of jaundice is examined in good daylight. The skin of forehead chest,
more likely to result into benefit than harm. There is no abdomen, thighs, legs, pahns and soles should be bl~ched
clear-cut demarcation between pathological and physio- with digital pressure and the underlying color of skin and
logical jaundice. TSB levels have been arbitrarily defined as subcutaneous tissue should be noted.
pathological, if it exceeds 5 mg/ dL on first day, 10 mg/ dL Serum levels of total bilirubin are approximately
on second day, or 15 mg/ dL thereafter in term babies. 4-6 mg/dL (zone l), 6-8 mg/dL (zone 2), 8-12 mg/dL
Such jaundice warrants investigation for the cause and (z?ne 3), 12-14 mg/dL (zone 4) and >15 mg/dL (zone 5)
therapeutic intervention such as phototherapy. Appearance (Fig.
.
9.42). Yellow
.
. a danger
staining of palms and so es is
1
of jaundice within 24 hours, TSB levels above the expected sign and requires urgent serum bilirubin estimation and
normal range, presence of clinical jaundice beyond 3 further management. In general, the estimation of bili.rubin
weeks and conjugated bilirubin (dark urine staining the levels by dermal zones is unreliable particularly at higher
nappy) would be categorized under this category. TSB levels, after phototherapy and h . . . d t
b · · w en it is carne ou
Presence of any of the following signs indicates by an mexdpene~ced observer. Total serum bilirubin can
pathological jaundice: e assesse non-mvasively by a tr dh Jd
device. anscutaneous han e
• Clinical jaundice detected before 24 hours of age
• Rise in serum bilirubin by more than 5 mg/ dL/ day Measurement of Blllrubln Levels
• Serum bilirubin more than 15 mg/dL Newborns detected to have y 11 di th
• Clinical jaundice persisting beyond 14 days of life skin beyond the legs or h e .ow 'scoloration of e
' w en therrcr · n
• Clay-/white-colored stool and/or dark urine staining levels approach phototh uuca Y assessedTSB
the clothes yellow confirmation of total ser~r~~?' ra:11ge, should have Jab
• Direct bilirubin >2 mg/ dL at any time a marked interlaboratory . rrubm. TSB assessment haS
vanability.
j 169 -
Yes No
+
Start phototherapy
+
Step 2: Does the infant have significant
jaundice to require serum bilirubin measurement'?
Yes No
Measure serum bilirubin and determine if baby requires Continued observation every 12 hours
phototherapy or exchange transfusion (refer to Table 9.21)
Step 3: Determine the cause of jaundice and provide supportive and follow-up care
breastfeed frequently and exclusively. Mother should be jaundice, extravasated blood (cephalohematoma), ongoing
told to bring the baby to the hospital, if the baby looks hemolytic disease, G6PD deficiency and hypothyroidism.
deep yellow or palms and soles have yellow staining. One should rule out cholestasis by noting the urine and
There is no use to expose the baby to direct sunlight to stool color and checking the level of direct bilirubin. If the
reduce hyperbilirubinemia. baby has dark urine or significant jaundice, investigations
Any newborn discharged prior to 72 hours of life should should be initiated to rule out:
be evaluated again in the next 48 hours for assessment of i. Cholestasis (stool color, urine color, direct and indirect
adequacy of breastfeeding and progression of jaundice. bilirubin levels)
ii. Ongoing hemolysis, G6PD screen
Pathotoglcaf Jaundice iii. Hypothyroidism
Term and near term neonates: The American Academy of iv. Urinary tract infection
Pediatrics (AAP) has laid down criteria for managing
babies with elevated serum bilirubin (Figs 9.44 for 25 25
phototherapy and 9.45 for exchange transfusion). Both the
Figs have age in hours on the X-axis and TSB levels on Y-
:::J
:!;'! 20
I_ 20
.§'. i
axis. There are three curves on each Fig. representing three c:
I
:i5 15 15 '5
risk categories of babies defined by gestation and other .~
risk factors. Risk factors refer to hemolysis, asphyxia, :a
E 10
I··
I
10
°'E
acidosis, low alb~min level, G6PD deficiency, hypothemia 2
Q)
en
and sickness. ]j 5 5
~
Pretenn neonates: Table 9.21 provides cutoffs for exchange
0
transfusion and phototherapy in preterm neonates below ~s~1rt:h~~24~h:---4~B:h~~7T2~h~-+-~-{-.:...:.~+-~-!-1 o
96 h 5 days 6 days 7 days
35 weeks of gestation. Age
..
......
Newborn Infants 171
~I
30 30 reaction is directly proportional to dose of photo-
,, I
~
I I 'A
therapy. This product forms 2-6% of TSB which is
rapidly excreted from body thus is mainly responsible I
~ -l
°'25
.§. I 6- 25
for phototherapy-induced decline in TSB.
:c"
2
~ 20
I b 20~ ..J
• Photo oxidation: This is a minor reaction, where
E photo-products are excreted in urine.
2
~ 15 Types of plzototherapy ligl1ts: The phototherapy units
/ 15
~ / available in the market have a variety of light sources that
include fluorescent lamps of different colors (cool white,
10B.1rth 24 h 48 h 72 h 96 h 5 days 6 days 7 days
10 blue, green, blue-green or turquoise) and shapes (straight
Age or U-shaped commonly referred as compact fluorescent
fig. 9.45: Guidelines for exchange transfusion In infants 35 lamps, i.e. CFL), halogen bulbs, high intensity light-
weeks' gestation or more. (A) Infants at lower risk (>38 weeks emitting diodes (LED) and fibroptic light sources.
and well); (BJ Infants at medium risk (>38 weeks+ risk factors or With the easy availability and low cost in India, CFL
35-37 6/7 week and well) and (C) Infants at higher risk (35-37 6/ phototherapy is being most commonly used device. Often,
7 week + risk factors) (Adapted from MP 2004) CFL devices have four blue and two white (for exami-
nation purpose) CFLs but this combination can be replaced
r:;- - ~~ -
Table 9.21: Suggested TSB cut-offs for phototherapy and with 6-blue CFLs in order to increase the irradiance output.
exchange transfusion in preterm infants <35 weeks
• I
In last couple of years, blue LED is making inroads in
Gestation (completed Phototherapy Exchange transfusion neonatal practice and has been found to equally effective.
1
weeks) LED has advantage of long life (up to 50,000 hours) and is
<28 5-6 11-14 capable of delivering higher irradiance than CFL lamps.
28 to 29 6-8 12-14 Maximizing tlie efficacy of pl1ototl1erapy: The irradiance
30 to 31 8-10 13-16 of phototherapy lights should be periodically measured
and a minimum level of 30 microW I cm2 /run in the wave-
32 to 33 10-12 15-18
length range of 460 to 490 nm must be ensured. The lamps
34 12-14 17-19 should be changed, if the lamps are flickering or ends are
Use postmenstrual age (for phototherapy for example, when a 29 week blackened, if irradiance falls below the specified level or
infant Is 7 days old, use the TSB level for 30 weeks). as per the recommendation of manufacturers.
(Adapted with permission from Maisels et al, Jour Perinatol, 2012)
Expose maximal surface area of the baby (Fig. 9.46).
Avoid blocking the lights by any equipment (e.g. radiant
Phototherapy warmer), a large diaper or eye patch, a cap or hat, tape,
Phototherapy remains the mainstay of treating dressing or electrode, etc. Ensure good hydration and
hyperbilirubinemia in neonates. Phototherapy is highly nutrition of the baby. Make sure that light falls on the baby
effective and carries an excellent safety track record of over perpendicularly, if the baby is in incubator. Minimize
SO years. It acts by converting insoluble bilirubin interruption of phototherapy during feeding sessions or
(unconjugated) into soluble isomers that can be excreted procedures.
in urine and feces. Many review articles have provided
detailed discussion on phototherapy-related issues. The
bilirubin molecule isomerizes to harmless forms under
blue-green light (460-490 nm); and the light sources
having high irradiance in this particular wavelength range
are more effective than the others.
For phototherapy to be effective, bilirubin needs to be
Present in skin so there is no role for prophylactic
Phototherapy. Phototherapy acts by several ways:
• Configurational isomerization: Here the Z-isomers of
bilirubin are converted into E-isomers. The reaction is '·
~tantaneous upon exposure to light but reversible as
bihrubin reaches into the bile duct. After exposure of 8-
12 hours of phototherapy, this constitutes about 25% of
TsB, which is nontoxic. Since this is excreted slowly from ·.
body, this is not a major mechanism for decrease in TSB.
• Structural isomerization: This is an irreversible reaction Rg. 9 .46: A jaundiced baby receiving phototherapy with two
Where the bilirubin is converted into lumirubin. The overhead units and blllblanket pad (arrow)
l'tt
- 172
Management
The baby should be nursed supine or in an upright
position and esophageal pouch should be gently sucked
every 5 minutes, or continuously using a slow suction
device. Intravenous fluids should be administered and
infection, if any, should be treated. Surgical repair should
be undertaken as early as possible.
Anorectal Malformation
A variety of anorectal anomalies have been described
(Fig. 9.48b). These may be anatomically classified as high,
intermediate or low. The position is determined by the
relation of terminal part of bowel to the puborectalis sling.
High or intermediate lesions are more common in males.
An X-ray film of the abdomen is obtained 12-24 hours
after birth, with the baby being kept in an inverted
position. A lateral picture of the pelvis should be obtained
to define whether the rectal pouch is above or below a
Fig. 9.47: Esophageal atresia with tracheoesophageal fistula. line drawn from the pubis to the coccyx.
Note the radlopaque catheter at T4 level (arrow). There is a Treatment is surgical. Prognosis is better with low
double gas bubble sign indicating presence of concomitant defects. About 80 to 90% of patients become continents
dueodenal atresia. after surgery for low defects. More than two-thirds of
patients are incontinent after surgery of high defects.
c
~g, 9.48: Various congenital malformations: (a) Congenital hydrocephalus; (b) Anorectai malformation; (c) Tuft of hair overlying
lh Underlying neural tube defect; (d) Menlngocele
I •
i
- 174 Essential Pediatrics
Diaphragmatic Hernia
Cleft lip is recognized readily (Fig. 9.49), ~ut a .careful Diaphragmatic hernia occurs because of failure of closure
inspection of the oral cavity is necessary to identify cleft of the pleuroperitoneal membrane. This allows intestinal
palate. A cleft of the soft palate can be e.asily missed unless loops to ascend to the thorax that compress the developing
the baby is examined carefully. Ve~tncular septal defect lung and can result in pulmonary hypoplasia (Fig. 9:50).
is a common associated anomaly with cleft palate. These babies can present at any time after birth. At b1r~,
a baby may be suspected to have diaphragmatic henua,
if there is respiratory distress and a scaphoid abdomen.
Bag and mask ventilation should be avoided in these
babies. Surgical repair after stabilization is the treatment
of choice.
_RAN
T~_ SP_O~R~T_O
~F:_:_:
N~EO=~:.=...:.:l~E~S~~~~~~~-----
Transport is an important component of sick newborn
care. It requires careful attention to vital pararneters,
temperature and blood glucose levels as well as
coordination with the receiving hospital (Fig. 9.51).
If the birth of an at-risk neonate is anticipated, the
mother should be transported (in utero transport) to a
facility with optimum maternal and neonatal care before
delivery (in utero trans fer). However, if referral of:
neonate is unavoidable, efforts should be made to do th
Ag. 9.49: Unilateral cleft lip and cleft palate best possible job.
..
175 -
-
Baby
+
Prepare for transport
corrected age. Initially, semisolids should be advised
in accordance with the local cultural practices.
ii. Growth 111011ilori11g: Growth (including weight, head
Stabilize (t~mperatu~e. airway, breathing, circulation and blood su ar
secure IV hne and give necessary treatment b f t g ) circumference, midarm circumference and length)
·r s
Log1s 1c
e ore ransfer
should be monitored and plotted on an appropriate
counsel ~he par~nts and family before transport growth chart at each visit.
communicate.with ref~rral facility. Provide a brief note
Arrange supplies, equipment and transport vehicle iii. Droelopmental assessment: Assessment of developmental
- + milestones should be done according to the corrected
. Care during transport age. The milestones should be assessed in four
Monitor frequently (temperature, airway and breath'n
1
· I r domains-gross motor, fine motor, language and
IV cannula and infusions) g, circu a ion,
personal-social. Infants who lag behind in any
Ensure that the baby receives feeds or fluid
Stop the vehicle, if necessary, to manage problems domain should undergo a formal developmental
evaluation. Age appropriate stimulation should be
+ provided to these babies.
. . Feedback after transport
Communicate with referral team for condition at arrival and outcome iv. Immunization: Immunization should be ensured
• lnd1cat1ons may vary as per the facility
according to chronological age.
v. Ongoing problems: Ongoing morbidities, such as
Fig. 9 .51 : Transport of sick neonates diarrhea, pneumonia, occur more frequently in these
babies and should require appropriate treatment.
FOLLOW-UP OF HIGH-RISK NEONATES
vi. Neurological assessment: Muscle tone should be
Improved perinatal and neonatal care has resulted in assessed, any asymmetry between the extremities
improved survival of many sick and small neonates who
are at-risk for long-term morbidities such as growth
failure, developmental delay and visual/hearing
problems. A proper and appropriate follow-up program
would help in prevention, early detection and appropriate
should also be recorded. Any history of seizures or
involuntary movements should also be recorded.
vii. Hearing and vision evaluation: High-risk infants have
higher incidence of moderate to profound hearing
loss (2.5-5% versus 1%). Since clinical screening is
I
management of these problems, thereby ensuring often unreliable, brainstem auditory evoked
disability and morbidity free survival. responses (BAER/ BERA) should be performed
between 40 weeks PMA and 3 months postnatal age.
Who Needs Follow-up Care? Vision of the baby should be checked at 9 months.
Table 9.22 lists the cohort of high-risk infants who require
followup services. METABOLIC DISORDERS
Hypoglycemia
What should be Done at Follow-up?
Hypoglycemia is defined as a blood glucose value of less
i. Assessment of feeding and dietary counseling: Parents
should be asked about the infants' diet and offered than 40 mg/dL (plasma glucose less than 45 mg/dL).
dietary counseling at each visit. Breastfeeding Screening for hypoglycemia is recommended in high
frequency and adequacy should be assessed. The risk situations (Table 9.23). These babies should be
amount, dilution and mode of feeding should be screened for hypoglycemia at 2, 6, 12, 24, 48 and 72 hours
after birth with reagent strips (dextrostix). Babies showing
fTabte 9;22: commoo .n ewborn conditio~s requiring high-risk blood sugar value of less than 40 mg/ dL on reagent strip
l!0 11ow-up care .· .. .. . · . should be treated for hypoglycemia but should have
Birth weight g' andto~·gestation' <32 week~··
<1.SOO ~~- confirmation of hypoglycemia by a lab test as reagent
:'.erinatal asphyxia: Apgar score ~3 at 5 min and/or hypoxic-
; ischemic encephalopathy .· · · Table 9.23: Common causes of ·hypoglycemia • 1 ..
Mechanical ven°tilation for·>24 hours ' Inadequate s~bst;;te:. S~ali for gestationai a·g·e (;eight for'
1 gestation <3rd percentile), gestation <35 weeks, birth weight
Metaboiic problems: Symptomatic hypoglycemia and
hypocalcemia . · · <2000 g .
: Infection$: Meningitis and/or culture positive sepsis Relative hyp~rins~linemia: Infants of diab~tic mother, large ' f~r·
\.HYPert?ni°rubin~mia >20 mg/dL or 'requirement ~! . ex9ha~ge
: date baby (weight for gestation >97th percentile). · ·
.!r~n~fus~on · ·. · -~,....: ·. ·:,:: , ...... _ ... , ! ..' ..... . i I Si~kness: Hypothermia, se.psis, asphyxia •
I# ~ ! ~.t!..... : ;,
- 176 Essential Pediatrics ~
. h hi h . F tus may die suddenly during the last trirn""'t ,,,..
strips ave ·g false positive rates. Appropriate for 1. e '""er
gestational ~ge babies who are breastfeeding adequately pregnancy f th b d Of
do not reqmre any screening for hypoglycemia. ii. Macrosornia or large. size o. e o y (Fi~. 9.52)
its attending risks d unng de~bvili~~ suchf as huth trail~
Cllnlcal Features ·a and increased poss1 ties o cesarean ~'lit,
asph YXI 5ecti
Clinically, the hypoglycemia may be asymptomatic or may ... H'gher risk of congenital anomalies. (Infant Oii
lll. I • 20 t. S Of
manifest with a range of clinical features like stupor, mothers with diabetes are 1mes more at risk
1
tremors, apathy, cyanosis, convulsions, apneic spells, develop cardiovascula~ defects.) o
~achyp~ea, weak and. high-pitched cry, lethargy, difficulty .IV. Neonatal respiratory distress
m feedmg, eye rolling, episodes of sweating, sudden v. Metabolic problems such as hypoglycemia and
pallor, hypothermia and rarely, cardiac arrest. hypocalcernia . .
vi. Polycythemia, i~creased v1scos1ty of blood and
Management of Hypoglycemia hyperbilirubinemia
Prevention of hypoglycemia: All high-risk babies should
receive proper breastfeeding, counseling and support. Pathogenesis
Adequacy of breastfeeding should be assessed and small Maternal hyperglycemia leads to fetal hyperglycemia and
babies not able to suck effectively on the breast, should that in tum leads to fetal hyperinsulinemia (Pederson
receive expressed breast milk by alternate methods. hypothesis). Insulin is an anabolic hormone and promotes
Asymptomatic babies: If the blood sugar is more than growth. Excess maternal glucose and amino acids provide
20 mg/ dL in an asymptomatic baby, a trial of oral feeds is the substrate for increased synthesis of protein, lipids and
given and blood sugar be tested after 30--45 minutes. If glycogen in the fetus. Large fetal size is mostly due to the
repeat blood sugars values are above 40 mg/ dL, frequent accumulation of fat.
feeding is ensured with 6 hourly monitoring of blood
sugar for 48 hours. However, if blood sugar values persist
below 40 mg/ dL, baby should receive IV glucose infusion.
If the initial blood sugar value is less than 20 mg/ dL,
I
then intravenous glucose infusion is started.
Symptomatic babies: A bolus of 2 mL/kg of 10% dextrose
should be given, followed immediately by glucose
infusion at an initial rate of 6 mg/kg/min. Blood sugar is
checked after 30-45 minutes and then 6 hourly. Repeat
hypoglycemic episodes may be treated by increasing the
glucose infusion rate by 2 mg/kg/min until a maximum
of 12 mg/kg/min. If two or more consecutive values are
>50 mg/ dL after 24 hours of parenteral therapy, the
infusion can be tapered off at the rate of 2 mg/kg/min
every 6 hours, with glucose monitoring. Tapering has to
be accompanied by concomitant increase in oral feeds.
Diabetes Mellltus
Diabetes is one of the most common endocrine disorders
affecting women during pregnancy. The following
Ag. 9.52: (a) Infant of d 1' b . · -- · e of
complications are likely to occur during pregnancy of a the baby with broad sh ~ etic mothe r. Note the large~lief
diabetic mother. head; (b) Hairy pinna ofuthders and torso and a relotiVelY
0 e baby
1111 -
Management is at risk to acquire infection from the mother. Such babies
The infant should be screened for malformations and should not be separated from the mother. Exclusive
injuries. Frequent breastfeeding should be encouraged. breastfeeding is encouraged. The infant should be given
The neonate should be monitored for blood glucose levels isoniazid prophylaxis (5 mg/kg/ day) and is evaluated at
during first three days of life. The other morbidities such 6 weeks of age. If there is any evidence of tubercular
as respiratory distress, hyperbilirubinemia sho~ld be infection in the baby (clinically or radiologically), the infant
treated appropriately. should be started on antitubercular therapy. If the infant
does not have any evidence of tuberculosis at 6 weeks,
Hypothyroidism the isoniazid therapy continued for 6 months and the infant
Hypothyroidism during pregnancy, if treated adequately, given BCG vaccine after 2 weeks of cessation of therapy.
does not affect pregnancy outcomes; however, inadequate
treatment of the mother predisposes the fetus to adverse Hepatitis B Infection
neurodevelopment. Neonate should be screened for Women who have hepatitis B infection (active or carrier
hypothyroidism using either cord blood or on blood stage) can transmit the infection to their babies. Such
sample taken after 72 hours of birth.
babies should receive hepatitis B vaccine within 12 hours
Tuberculosis of birth, which can prevent perinatal transmission of
hepatitis B virus significantly. Hepatitis B immuno-
If the mother has active pulmonary tuberculosis that has globulins (HBIG; 100 IU, IM) can be given to enhance
been treated for less than 2 months before birth or the the protection but it is costly and there are availability
diagnosis of tuberculosis was made after birth, the baby issues.
' .
Chapter
10 Immunization and
Immunodeficiency
Aditi Sinha •. Surjit Singh
Table 10.1: Causes of secondary Immunodeficiency Table 10.2: Work-up for suspected immunodeficiency
Human Immunodeficiency virus Infection - Screening investigations
following measles Total and differential leukocyte counts, leukocyte morphology,
severe malnutrition platelet count and size
Nephrotic syndrome HIV serology; X-ray chest
Lymphoreticular malignancies Specific investigations
severe burns Quantitative immunoglobulins: lgG, and subclasses: lgA; lgM;
Drugs: Glucocorticoids, cyclophosphamide, azathioprine,
lgE
diphenylhydentoin Blood group isohemagglutinins (for functional lgM)
severe, chronic infections Anti-diphtheria and anti-tetanus antibodies (functional lgG}
CD3, CD4, COB, CD19, CD16, CD56 by flow cytometry
clinically important causes of secondary immuno- CD18, flow cytometry (leukocyte adhesion defect)
deficiency. Bruton tyrosine kinase protein; Wiskott-Aldrich syndrome
Primary immunodeficiency disorders can affect any of (WAS) protein
the major components of immune system, including T Mitogen stimulation tests (e.g. response to phytohemagglutinin}
and/or B lymphocytes, antibody production, phagocyte Nitroblue tetrazolium dye reduction test, and dihydrorhodamine
number or function and complement components. The assay on flow cytometry, CGD
condition should be suspected in patients presenting with CH50, and AH50 assays and levels of complement component
~of the following 10 warning signs: (i) ~4 new infections Mannan binding lectin assay
in a year; (ii)~ serious sinus infections in a year; (iii) 2".2 Enzyme assays, e.g. adenosine deaminase, purine nucleoside
cases of pneumonia in a year; (iv) 2".2 months of antibiotics phosphorylase
without effect; (v) failure of an infant to gain weight or Delayed skin tL ts (Candida , Tetanus toxoid)
grow normally; (vi) recurrent deep skin infections or organ AH50: Alternate pathway complement hemolytic assay; CD: Cluster
abscesses; (vii) persistent oral thrush, or candidiasis differentiation; CGD: Chronic granulomatous disease; CH50: Total
elsewhere beyond infancy; (viii) need for IV antibiotics to hemolytic complement assay; HIV: Human immunodeficiency virus
clear infections; (ix) ~2 deep-seated infections (e .g.
meningitis, cellulitis); and (x) family history of ranging from mildly increased susceptibility to infections
immunodeficiency. to severe disease requiring thymic or hematopoietic stem
Tables 10.2 and 10.3 outline the workup and clinical cell transplant.
findings in various disorders. Conditions that mimic Wiskott-Aldric1z syndrome (WAS): This X-linked recessive
immunodeficiency (e.g. gastroesophageal reflux, disorder is caused by mutations at Xpll.22-23, encoding
Kartagener syndrome, cystic fibrosis) should be excluded. the WAS protein in the cytoplasm of lymphocytes and
platelets. Eczema begins in early infancy and may mimic
Cellular and/or Combined Immunodeficiency atopic dermatitis. Thrombocytopenia is associated with
Severe combined i1111111modeficie11cy (SCID): Children with small-sized platelets. Due to impaired responses to
SCIO present in early infancy with severe infections due polysaccharide antigens, patients are susceptible to
to viruses, fungi (e.g. P11e11moet;stis jirovecii) or intracellular infections with pneumococci, meningococci and
pathogens (e.g. Mycobacteria). Tonsillar tissue is usually Haemophilus injluenzae. The clinical phenotype varies; some
absent and lymph nodes are not palpable. Left untreated, children have a fulminant course with repeated severe
such babies do not live for more than a few months. infections (WAS spectrum), while others present later,
Profound lymphopenia is characteristic. The most predominantly with bleeding manifestations (X-linked
common form of SCIO is X-linked and is caused by thrombocytopenia spectrum). The risk of lymphoreticular
mutations in the common gamma chain [of interleukin malignancies is increased. There is severe IgM deficiency
2 (y)]; approximately one-fourth cases have adenos~ne in addition to defective T cell signaling, secondary to
deaminase deficiency. SCIO due to purin~ nu~leoside deficient expression of CD43 in lymphocytes.
-·
P~osphorylase deficiency may present later m childhood Ataxia-telmrgiectasia: This autosomal recessive disorder
With milder features. is characterized by progressive ataxia (beginning during
D·G f
e 1 eorge auomaly: This disorder arises from de ects m
. infancy), telangiectasia (initially on bulbar conjunctiva),
sinopulmonary infections, chromos~m~l breakage an~
l~·bryogenesis of third and fourth pharyngeal pouch.es.
increased sensitivity to ionizing radiation. The gene is
(h 18 characterized clinically by an unusual facies
localized to chromosome llq22-23; its product regulates
JPertelorism, antimongoloid s lant, low set ear~,
the cell cycle. The degree of immunodeficiency is less
te~gnathia, short philtrum, bifid uvula), hypocalcem1c
profound than in Wiskott-Aldrich syndrome. Serum IgA,
•d . "f, aortic arch anomalies and absent thymus. In
IgG2 subclass and IgE levels are usually reduced;
clition, 20-30% patients show a variable T cell defect, ·
Ill 100 I ~~~~~~""--_________!Bt~•~o~nl~ln~l!P~nc~Jln~t~rlo~1~------------------~~-----....
- - -.. .- ~-· · .-~-·- ~ - · · TabI•·10.31 Cllnloi l oluoa to tho dlngnonl!I of r>rlmory tmmunodetlolency .
Type of Infection Agn EU IJl'f1tu'Jllfllllon Anooolt1tod f/nclln(JtJ Likely otlo/ogy
Pneumonia or diarrhea; crypto· l"lrnt row monllHI Pt1lluro to llirlvo; ri:rnh; Severe combined lmmuno-
sporldlosls; disseminated ElcO I"feelIcm ,,.
Of llf"' ••tronl1lo
11 ,.
IC
>ll"'llA
,, ..,
nnd deflcloncy
lymph nodoB
4- Gmont110 Only hoyt1 offooto<J; rf.llluro X·llnkod agammaglobulinemla
Pneumonia; pyogenlo lnfectloM
(S. pneumonlse, H. lnflw:mzae) lo lhl'IVO
Hopototiplonomoooly; Common varlable
Diarrhea, slnopulmonary Infections; ofhm Lutor ol1lldhood
lyrnplloc.Jonopnthy Immunodeficiency
pyogenlc (S. pneumonlae, H. lnflum1ti1.tJ) (>5~'!0 yM rn)
Cooroo tnolnl foaturoo, Hyper-lgE syndrome
Recurrent staphylococcal cold absMssGs, Ally ogo
pneumonia (often with pneumatoeele) oozonmlouo rooll
Recurrent or persistent glardlasls Any aoo Aulolmmuno dleoaooo lgA deficiency
lymphocyte proliferative responses llt'e decrensed nnd H1c mny bl~ responsible: Inducible costirnulator (/COS); CD19;
number of yo-positive T cells is incrensed. CDW; CD8'1 ; 13 cell-activating factor of tumor necrosis
Hyper-IgM syudrome: This syndrnme cnn result from fnctor fnmily receptor (BAFF-R), tumor necrosis factor
ogam.mnglobulinemif\ is prolonged to 18-21\ monlhA, e:oll'lmox111.utu) IH rnqulrod fm rmmo chlldro1\ with JgGl
ut.ting m transient hypogammnglobulhwmtn of lnfom:y.
1 1rnd l~C:~\ tiuhclmm duflcluncy. '
~m IgG levels in infoncy nnd cnrly childhood Ahould /,,1111~- l1•r111 col rl lllO.\'awlr: a11d // mcv111rwlc! 111·vµ/1ylt1.\'/s hns
i.nterpreted in context of 11gc·rcl11ted nomORl'l\l\lS. lmpl'\Wl1d the l\lllllllgl.'llll'nl of d1ro11/c sm1111/0111alo11:11/lscmw.
tbkeX-linked n?mmnnglobu\tncmia, Uccll m11nbo1·R 111·0 l11kt:f1•ro11 -y l::i 11t1cd fur lrcnlml'nl of llfc-thrl'l\lcnlng
irmal. !~ese cluldrcn recover ovc1· lime nnd lol\g·term lnfccllonH. J /1•11111t11110/1•tlc ~1f1!111 ct'// f r1111:1J1!1111talio11 Is
ognos1s is excellent. h\crc•nsl11gly wwd In p11lll nl9 with lhe dlse•1t1c. ,
1
II
Miscellaneous lVlg is therapy of choice for Kawa saki dise ase
Complemeut compo11c11t deficicucy: Individunls with idiop;1thic lhrombocytopcnic purpura and autoimmun~
deficiencies of the early complement components (C2-C4) demyclinnting polyradkuloncuropathy, dose being 2 g/kg
may present with recurrent bacterinl infections, while given in single or divided doses. IVlg is nlso replacement
those with deficiency of the lnter components (C5-C9) thernpy in vnrious forms of hypognmmaglobutinemia, the
have predilection for Neisserin infections. Systemic lupus dose being 0.4-0.6 g/kg every 3-4 weeks. Use of 1Vlg is
.erythematosus may occur in those with C2/C4 or Clq considered in severe mynsthcnin, lupus crisis, autoimmune
deficiency. Deficiency of Cl esterase inhibitor is associnted neutropenin, neonatal alloitnmunc and nutoimmune
with hereditary angioneurotic edema, chnrnctcrized by thrombocy topenin, dcrmntomyositis not responding to
onset of recurrent non-itchy swellings in the body. steroid thernpy, nnd certnin vosculitidcs. lVlg has been
used for prophylnxis nnd treatment of nconntnl sepsis in
Hyper-IgE syndrome: Mutations in STAT 3 gene result in low bir1'11 weight babies, with equivocal results.
recurrent 'cold' staphylococcal abscesses, pneumonia with Administrntion of lVlg mny be associntcd with ndverse
pneumatoceles, retained primary dentition and mnrkedly effects, including nnnphylnctoid and nnaphylactic (IgE-
elevated serum IgE concentration (>2000 IU /mL). mediated) rcnctlon::i. IV lg infus ion must be stnrtcd slowly
Inheritance is usually autosomal dominant. nnd the child monitored closely; infusion rate is slowed
Treatment of Primary Immunodeficiency Disorders or discontinued, if lhe child develops chills or rigors. The
risk of acute kidney injmy is negligible with current iso-
Hematopoietic stem cell tra11splm1tntio11 is the trentment osmolar prcpnrntlons. Long-term risks indudc lT.msmh;sion
of choice for most forms of significant cellular immuno- of hepnlitis C infection.
deficiency (e.g. SCID, Wiskott-Aldl'ich syndrome, hyper·
~gM syndrome). The procedure should be done in en~ly Suggested Re ading
infancy. Children with X-linked agammnglobulinemrn, • Gupln S, Mndklllknr M, Singh S, Scht~nl S. Pl'lmnry lmmuno~
lgG2 subclass deficiency nnd common variable imrnuno- ddlclcndci1 In lndln: /\ pcl'!!pcdlvc. Ann N Y Acnd Sci 2012;
~eficiency require administration of i11tr11vc11011 s 1250:73-9.
1mmunoglobuli11 (IVlg) every 3-4 weeks. Though expensive,
• Slnt;h S. /\pprnnc h to n pntlcnt with 11uspcctcd prlnrnry
lnmmnodcflclcncy dlt1ordcr. APl Textbook or Ml'l'tlclnc, 10th cdn.
therapy with IVlg results in satisfactory quality of life. Edt1. Mun]nl YP, Shnnna SK. Jnyp,•c Orolhcn1, New o,·lhl. 2015,
Patients with IgA deficiency do not require any specific
pp. 249-55.
therapy. Prophylactic tl1ernpy with nntimicroliinls (usually
II 184 Essontlnl Podlntrlcs
11
Fig. 10.1: Routes of vaccination. (a) Oral: Pollovlrus (attenuated), rotavlrus; (b) Intranasal: Influenza virus (live-attenuated):
(c) lntradermal: BCG, Inactivated pollovlrus (fractionated dose) and rabies; (d) Subcutaneous: Measles, mumps, rubella, varlcel\o.
yellow fever, Japanese encephalitis, menlngococcal and pneumococcal polysaccharlde, and Inactivated pollovi us:
(e) Intramuscular: Most vaccines, Including hepatitis A and B; diphtheria, tetanus and pertussis, H. lnfluenzae b, pneumococcol
polysaccharlde, Inactivated polio and Influenza
discoloration, particulate matter and inability to suspend young children with BCG, diphtheria and tetanus toxoids
the lyophilized powder. and whole cell pertussis (DTP or DTwP) and OPV
vaccines, and chiefly covered urban areas. The U11iversal
Vaccination Schedules and Immunization Programs Im1m111ization Programme (UIP, 1985) improved natiomvide
The choice of vaccines in national immunization schedules coverage of immunization and also included measles
is based on considerations of disease burden, vaccine vaccine. The Pulse Polio /1111111111izatio11 Programme (1995)
availability and cost-effectiveness, and program coverage enabled polio control. UIP has remained a key component
and sustainability. The Expanded Programme ofImmunization of the Child Survival and Safe Motherhood Programme
(EPI), introduced by the World Health Organization (1992), the Reproductive and Child Health Programme
(1974), was the first global immunization initiative. (1997) and National Rural Health Mission (NHRM, 2005).
Adopted by India in 1978, the EPI focused on vaccinating Efforts of UIP are supported by Child Vaccine Initiati\•e
Immunization and Immunodeficiency 1as I
Box l 0. l : Principles of Immunization 1978 Expanded Programme of Immunization (EPI) &'
, BCG, OPV, typhoid and DPT
• Different live (oral, parenteral, intranasal) vaccines may be 1
1983 Addition of IT vaccine
, given simultaneously, or at an ir\terval of 4 weeks. 1985 Universal Immunization Programme (UIP) 6
• Different types of inactivated or subunit vaccines may be Addition of measles vaccine; typhoid discontinued
administered simultaneously or at any interval between their Cold chain; nationwide implementation
doses. A minimum interval of 4 weeks between two doses of 1995 , Pulse Pollo Immunization Campaign . __
the same vaccine is necessary to ensure adequate immune 2002 Hepatitis B Immunization 7
responses. An exception is the rabies vaccine. Introduced in some states; nationwide by 2010
2006 Japanese encephalitis (JE) vaccine- • · 8
• There is no minimum recommended tin1e interval between · Only In endemic areas; 112 districts by 2010 _
two types of vaccines. Hence, a live and an inactivated 2010 Hepatitis B scaled up to entire country
vaccine can be administered simultaneously or at any Second dose of measles
interval of time. 1 2011 . Pentavalent (DPT+HBV+HIB) vaccine 9
· • When necessary, two vaccines can be given in the same limb · Introduced in some states 1
at a single visit, preferring the anterolateral thigh for ' 2013 Second dose of JE vaccine (in endemic districts)
simultaneous IM injections; vaccines are administered at 2014 · JE vaccine for adults (in endemic districts)
least 1-inch apart. 2015 Inactivated poliovirus vaccine (nationwide by 2016)
Mission lndradhanush (to improve coverage)
( • A delay or lapse in the administration of a dose does not 2016 Rotavirus vaccine (in some states) 11
'f require . the schedule to be repeated; the missed dose is Human papillomavirus vaccine (in some states) .
. administered and the course resumed at the point it was 2017 Measles-Rubella Vaccination Campaign 13
! interrupted. 1 Intensified Mission lndradhanush
Pneumococcal conjugate vaccine (in some states)
' • Vaccines should not be mixed in a syringe unless approved
by the manufacturer. Fig. l 0.2: Milestones in the National Immunization Programme.
• Patients should be observed for allergic reactions for 15-20 The program that started with four vaccines against six infectious
' minutes after receiving immunization. Illnesses now provides coverage against 13 childhood Infections.
• Immunization is not contraindicated in minor illness,
prematurity, allergies, malnutrition, exposure to infection Programme, but recommends certain additional vaccines
and antibiotic therapy. based on regional burden of vaccine preventable diseases
· • Live vaccines are contraindicated in inherited or acquired and the availability, safety and efficacy of various vaccines
immunodeficiency and during therapy with irnmuno- (Table 10.7). Figure 10.3 compares the national programs
suppressive drugs, but may be given after a short (<2 weeks) and recommendations of the IAP.
course of low dose steroids.
• Immunoglobulins interfere with the immune response to
COMMONLY USED VACCINES
certain live vaccines like mumps, measles and rubella, but
not OPV, yellow fever or oral typhoid vaccines. The following section describes vaccines recommended
· • Hepatitis B, tetanus toxoid and rabies vaccine may be given in the national immunization program or Indian Academy
concurrently with corresponding immunoglobulin. of Pediatrics for normal children and certain high-risk
' • Active immunization should follow exposure to rabies, groups.
· . measles, varicella, tetanus and hepatitis B.
BCG Vaccine
and Global Alliance for Vaccines and Immunization (GAVI).
Bacillus Calmette-Guerin (BCG) vaccine contains bacilli
Figure 10.2 and Table 10.6 depict milestoz:es in the national
derived from s ubcultures of live-attenuated M . bot1is
immunization program and current national schedule.
Calmette-Guerin strain. The vaccine used in lndia is the
Mission Indrad11an11sh: Despite the UIP being operational Copenhagen (Danish 1331) strain produced at Guindy
for three decades, recent surveys indicated that only 65% (Tamil Nadu) and available as lyoph ilizcd powder in
of infants received full immunization coverage. In 2014, vacuum-sealed dark multidose vials. When reconstituted
the Government of India launched 'Mission with sterile normal saline, each dose (0.1 ml) contains 0.1-
Indradhanu sh' to strengthen UIP and achieve full 0.4 million live viable bacilli. This heat and light sensitive
immunization coverage rapidly (Box 10.2). The mission vaccine is stable in lyophilized form at 2- 8°C for one year,
derives its n ame from the seven diseases prevented but loses potency rapidly when reconstituted.
through these vaccines (BCG, OPV, pentav~le~t and TT BCG vaccine primarily induces ce ll-mediated
vaccines) and focuses on complete immumzahon of all immunity. Meta-analyses estimate that the vaccine has low
children less than 2-year-old and on pregnant women. protective efficacy agains t primary infection (-40%),
pulmonary infection (8-79%) and all forms (-50%) of
Immunization Schedule of the tuberculosis . However, it enables satisfactory (>50%)
Ind/an Academy of Pediatrics (/AP) protection against severe forms of tuberculosis (mili~ry
The IAP Advisory Committee on Vaccines and Imm_uni~a tuberculosis, tubercular meningitis) and reduces the risk
ti.on Practices (ACVIP) endorses the National Immuruzation of mortality. As childhood tuberculosis accounts for 15-
- 186
"fable 1·0.6:- immunization sohedulo In Indio bofore and after phased lntrod.lfcdon of tWH vacdnet
'. Age Schodulo In 2010 Schedule Jn 2017
At birth BCG, OPV·O, HBV·O BCG bOPV·O, HE3V-O
6 weeks OPV-1, DTP·1, HBV·1 bOPV·1, P~ntavaJ~nt-1, Aota·1·. flPY·1 . PCY-~·
10 weeks OPV·2, DTP-2, HBV-2 bOPV-2, Pentavalent·2, Aota-~
14 weeks OPV·3, DTP·3, HBV·3 bOPV·3, PentavaJent·3, Rota·3·, flPV-2., PC'l,z
9 months Measles-1, JE-1* MA·1·, JE·1', PCV·3·
16-24 months Measles·2, DTP·B1, OPV·B DTP·B1, bOPV·B, JE·~. MR·T
5-6 years DTP·B2 DTP-82
11-13 years HPV·1, HPV·2·
B: Booster; BCG: Bacillus Calmette-Guerln; bOPV: Blvalont oral pollovlrus; DTP: diphtheria, pertueeis, tmnus; flPV: Fraotiomd91 imi~:r&t;,::J
poliovirus; HBV: Hepatitis B virus: HPV: Human paplllomovlrus; JE: Japanaso ancophalltis; MR: Meaeles, rubella; PC'/: Pn~!JflYJO"JCX:al con~
vaccine: Pentavalent: DTP+HBV+ Haamop/1/lus lnf/uonzae b; Rota: Rotavlrue
•where implemented
~.
Box 10.3: Bacillus Calmette-Guerin (BCG) vaccine
routt• 0.1 mL; intradermal
Age Schedule" Site.• Left upper arm at insertion of deltoid
At birth BCG, bOPV-0*, H8V-1 Sdrt•dulc!
National program At birth; catch up till 1-yr (if missed)
6 weeks IPV-1*, H8V-2*, DTP-1, Hib-1, Rota-1, PCV-1
10 weeks IPV-2*, DTP-2, Hib-2, Rota-2, PCV-2 IAP 2016 At birth; catch up till 5-yr
14 weeks IPV-3*, DTP-3, Hib-3, Rota-3, PCV-3 Adt't'~t· n:nctio11s Local ulceration; discharging sinus;
6 months bOPV-1*, H8V-3* axillary lymphadenitis
If immunodeficient, disseminated
9 months bOPV-2*, MMR-1, Typhoid (conjugate), JE-1s
infection, osteomyelitis; scrofuloderma
12 months IPV-81*, Hib-81, PCV-81, HAV-1*
Contrai11dicntio11 Cellular immunodeficiency; sympto-
.15 months DTP-81, MMR-2,Varicella-1 , JE-2s
18 months HAV-2* matic HIV
Stomge 2-8°C; sensitive to heat and light; ·
2-3 years Typhoid (conjugate)-8
discard reconstituted vaccine after 4 hr
4-6 years bOPV-3*, DTP-82, MMR-3, Varicella-2
11-12 year Tdap; HPV-1 & HPV-2* rates are lower in developing compared to developed
B: Booster; BCG: Bacillus Calmette-Guerin; bOPV: Bivalent oral poliovirus; countries.
OTP: Diphtheria pertussis, tetanus; HAV: Hepatitis A virus; HBV: Hepatitis Each dose (2 drops) of trivalent OPV contained 105-106
B virus; Hib: Haemophilus influenzae b; HPV: Human papillomavirus; IPV:
Inactivated poliovirus; JE: Japanese encephalitis; MMR: Mumps, measles,
median cell culture infectious doses of each serotype 1, 2
rubella; PCV: Pneumococcal conjugate; Rota: Rotavirus and 3. Type-specific immunity was associated with highest
'Preferred schedule detailed under respective vaccines, particularly seroconversion rates for OPV type 2, leading to eradication
where indicated by; of wild type OPV2 in 1999. Since this serotype inhibits take
'Influenza vaccine recommended annually and vaccination in high-risk of OPVl and OPV3, and most cases of vaccine-derived
groups not shown poliomyelitis (VDPV) are due to OPV2, as part of Polio
SOnly in endemic areas
Eradication and Endgame Strategic Plan 2013-18, trivalent
enteroviruses, concomitant diarrhea and interruptions in vaccine has been replaced by bivalent OPV (bOPV); OPV2
the vaccine cold chain. Vaccine 'take' and seroconversion use was globally discontinued in April 2016.
BCG ..
1'1.~
KEY
Schedule Recommended age Catch up Immunization
BCG Bacillus Calmette-Guerin; DTP diphtheria, pertussis, tetanus:
Universal Immunization Program only
IPV inactiVated poliovirus: MMR mumps, measles, rubella; OPV
lndlan Academy of Pediatrics only oral pollovirus; TI tetanus tox:oid
Both Schedules 'Boosters (B) as either whole cell or acellular vaccine; 83 as
Only in selected areas in UIP tetanus with reduced diphtheria and reduced pertussis (Tdilp)
Ag. 10.3: Vaccinations scheduled In Universal Immunization Program and Indian Academy of Pediatrics (2016). Details are under
respective vaccines
- 188 ~~~~~~~~~~~~~E~ss~e~n~tl~a~l!P~ed~l!at~rl~c!a ______ ~----------~~~~-~
Since OPV is very sensitive to tcmpcratmc, its potency Recommendations on Vaccination
is monilorL'd using vnccinc vial monitor (VVM), a heat Against Pol/ovlrus In Ind/a
sensitive patch on the vial lnbel (sec lion on Cold Chain). Since Februnry 2014, WHO no longer recommends an OPV
To dccl'L'asc ch.mces of vaccine foil me, at least three doses on1y sc11ed u le. This is because IPV, apart· from protecting
li
nre requin-d. ·I-~ WL'cks apart. The ndminislra\ion of 'zero' fromw1'Id typepoliovirus also protects f agamstpo
. . omyelitis
.
dose at birth L'nhances seroconvcrsion. Urcas tfceding and causedby cVDl'V2 (bOPV used. or routine . . immuruzation·
M 1
.
mild diarrhea arc not contraindications for OPV populationimmunityforOPV21s declining). o.stcounmes
administration. Children with immunodeficiency and prac t'ice a sequential ' IPV-OPV . schedule, APwhich
. . has. . the
pregnant women should not receive the vaccine; its use is advantage that the risk of OPV-mduc~d V P.is ffillUmized
also avoided in household contacts of these patients. by prior administration of IPV, ~hile ~ns~nng. adeqt~ate
ln the past, OPV vaccine was given simultaneously with mucosa! immunity to interrupt wild p~liovrrus circulation.
DPT vaccines at 6, 10 and 14 w eeks, followed by two WHO recommends t/iat all countries using only OPV should
booster doses with DTP boosters a\ 15-18 months and add at least one dose of IPV to the national schedule. The primary
5 years. Since 1995, children below 5 years also received series consisting of three OPV doses ~lus o~~ IPV ~ose can
the vaccine during the (sub-) national immunization days be initiated from the age of 6 weeks, with rmrumum mterval
and supplementary immunization actitivities in the Pulse of 4 w eeks between OPV doses. If one dose of IPV is used,
Polio campaign, wherein simultaneous administration of it is given at 14 weeks of age ~~ei:'- m~temal antibodies~ve
OPV to all young children in U1e community interfered diminishedandimmunogeruc1ty1shigher, oneofthemaior
with feco-oral transmission of the circulating wild objectives of the Polio Eradication and Endgame Strategic
poliovirus. Together with surveillance and targeting of Plan 2013-2018 (see below) is to introduce at least one dose
migrant populations and high-risk areas, wild poliovirus of IPV into routine immunization schedules, strengthen
was eradicated from India; the last wild polio case routine immunization and withdraw OPV in a phased
(serotype l) reported from Howrah in January 2011. manner, starting with OPV2.
While OPV is preferred for eradication of poliomyelitis, Evidence suggests that VDPV and wild type OPV may
the virus may regain neurovirulence, resulting in vaccine- surface 4 years and 10 years, respectively, after global
associated paralytic poliomyelitis (VAPP) in 1 of 1.5 cessation of OPV. Even after global OPV withdrawal,
million OPV recipients, chiefly with OPV3 (recipients) or national schedules should continue to provide at least two
OPV2 (con tacts) . Furthe r, outbreaks of paralytic doses ofIPV in their immunization schedule, administered
poliomyelitis may be caused by a virulent strain of either as full or fractional doses, for at least 10 years after
poliovirus formed by mutation of OPV, chiefly OPV2, OPV withdrawal. While efforts are ongoing to prioritize
called the circulating vaccine-derived poliovirus (cVDPV). IPV supply for use, experts suggest continuation of a 2·
Similnr to the wild virus, cVDPV spreads rapidly through dose fractional (fIPV) dose schedule, which ensures that
the community to cause outbreaks, especially in areas with all eligible infants receive IPV. This strategy is dose sparing
low or declining rates of OPV coverage. (one-fifth the IM dose) and results in better immuno·
genicity than a single intramuscular dose of IPV. Two
Inactivated Pollo Vaccine {IPV} fractional doses or two full IPV doses are required to
IPV is a suspension of formaldehyde killed (salk) achieve ~90% seroconversion, with the first dose given
poliovirus grown in monkey kidney, human diploid or ~14 weeks and an interval ~4 months behveen the first
Vero cell culture. The vaccine primarily induces humeral and second doses. Administering fIPV during routine
immune response, but pharyngeal and possibly, intestinal immunizaton visits at 6-14 weeks achieves high vaccine
mucosa! antibodies arc also induced. Vaccine potency is coverage and acceptability.
measured by its 'D' antigen content. Each dose of currently IPV was, therefore, introduced in India in 2015-16 with
used third generation or enhanced potency IPV (eIPV) two fractional (fIPV) intradermal doses at 6 and 14 weeks · '
vaccines contains 40D, SD and 320 units of types 1, 2 and (Box 10.4). Children continue to receive bOPV on all
3 polioviruscs, respectively, grow1~ in Vero c~ll ct.ilture ~ationa~ irr~muni~a~i~~ days and during supplement~r)'
and purified before inactivation. IPV is highly immuruzahon activities. Patients that m iss immunizatton
immunogenic; with seroconversion in 90-99% of infants. at 6 weeks receive a full intramuscular dose of JPV at
over 8 weeks old administered 2-3 doses 4-8 weeks apart. 14 weeks. The IAP accepts the above schedule as
Vaccination beginning at 6 weeks carries risk of :moderately .effective' against OPV2. It prefers the more
interference with maternal antibodies. Despite low titers immunogemc three-dose schedule or two intramuscular
of secretory JgA and weak induction of herd immunity, doses beginni~g at 8 weeks and' given 8 weeks apa:t
IPV has excellent efficacy in preventing poliomyelitis. IPV (Box 10.4; also footnote). IPV is the vaccine of choice lJl
administration has the advantage of not causing VAPP. · patients ~ith ~m.munodeficiency including symptomatic
Hence, following a phase of sequential or combined O~V HIV, and. m siblings and close contacts of such patients.
IPV use, countries with sustained eradication of circulating · Th~~ children should not receive OPV and receive all
wild poliovirus hnve switched to exclusive use of IPV. additional booster dose of IPV at 5 years. Both schedules
hnmunlxeHlon nnd lmmunodoflolonoy 1&9
llu~ \0.4\: lllV\llt11ll l1l\tl Jl!•ll<1Vlll1!1 (Ii< ll'V) <Hl<l lr1t11 .llVUlr1d r111llft/lfll'i (lf'/J /Uf/,tf ilr1
1
- . .
ret,1in the birth do$e of OPV; this dose is ncccssnry in nrens hydroxide, the ndjuvnnt. This is the most commonly used
with continued risk of wild vims trnnsmission, nnd Is vnccine. The qunntity of toxoid in the vaccine, expressed
unlikely to cau~c VAPP in presence of mnternnlly as limit of flocculnlion (Lf) content is 20-30 Lf of DT, 5-25
transmitted nntibodies.
world, developed b y the Globnl Polio Erndicntion lnitinlivc vncci nntion is begun within a few weeks of life and
in consultation with lwalth nulhorities, experts nnd other multiple closes arc given. Primary immunization with 3
stakeholden;. The plan addresses theerndicntion of all polio doses of the vaccine, given 4-8 weeks apart, induces
disease, caused by wild or circulating vaccine- derived sntisfoctory immune response to OT and IT in 95-100%
poliovirus. Its obj~('tivcs nre: (i) Dcll•ct and inll•rrupt all infants. Protective efficacy ngainst pertussis is lower, at
poliovirus transmission; (ii) strl'ngthcn immunizntion -70-90'X,, and wanes over 6-12 years. Immunization does
systems and withdraw OPV; (iii) contain poliovirus nnd not eliminate C. diplttherine from the skin or nasopharynx.
certify intermption of transmission; and (il•) plnn post-polio Booster doses arc required to s us tain a protective antibody
legacy (Fig. 10.4). .A midterm review suggests I.hat c~rtnin titer of 0.1 IU/mL and protect from disease in the first
activities require focus, including: ( o_strcng!llClllllg ~hse_asc dccnde of life. Naturnl infections and immunization
surveillance; (ii) improving quality of 1mmun1zol10n against pertussis induce immunity las ting 4-12 years,
campaigns; (iii) building cal~acit~ to respond to outb~·en~s. mnking boosters necessary to prevent infection in
A post-certification strategy 1s bemg ~evelop~d to m.am.t nm ndolcscence. Dox 10.5 indicates the sch ed ule for
a polio-free \·\1orld. Its gonls nre: (1) Contnm pohovu·us administration of DTwP or DTaP, containing OT, IT and
sources by ensuring thnt they nre propcrly controlled or acellulnr pertussis.
removed; (ii) prott'Ct populnlions by withdrnwing Ol'V and DTwP vaccine is commonly associated with local (pain
immunizing\·Vith lPV against possible re-emergence of nny nnd redness) and systemic (fever) reactions, chiefly
poliovims; and (iii) detect and respond promptly lo any nttributed to the pertussis component. The incidence of
poliovin1s reintroduction. these adverse effects increases with the number of doses
administered; hence the vaccine should not be used
Diphtheria, Pertussis and Tetanus Vaccine beyond 5 doses or beyond 7 years of age. DTP is also
Diphtheria vaccine contains diphthedn toxin .<DT) incriminated in rarely inducing of serious n eurological
inactivated by formalin and ndsorbl;)d on nlununum complications, though conclusive evidence is Jacking
- 190 Essontlnl Podlntrlca ---......._
Objoctlvoa Stratoglo1
Virus detocllon ond Wild
lnlorrupllon pollovlrus outllroilk msponiu~ mipauloUy oVOPV
lnlorr\lptlon
Slronott,on
Routine Immunization lmmunlznllon,
strengthening and octdross pre- lntrodltGtl IPV
OPV withdrawal roqulsltos for Wlthdrnw OPV2
OPV
wlthdmwnl
Consultation ond
Legacy planning lmplornontotlon of logocy pion
strategic pion
(Box 10.5). The vaccine is contraindicated in children with complete the immunization schl!dulc with OT tl\l\t
progressive neurological disease; children with stable contains the same doses of OT nnd TT ns DTP, but is
neurological diseases (e.g. developmental delay, cerebral devoid of the pertussis component. OT is rccomnwndrd
palsy and idiopathic epilepsy) may receive the vaccine.
up to the ngc of 7 ycnrs, beyond w hich Td must be usl'd.
Absolute contraindications to administration of the
vaccine and adverse events that require precaution are
listed in Box 10.5, if an event listed as precaution recurs Acellular Pertussis Vaccine (DToP)
Box 10.5: Dlpt1therla toxold, tetanus toxold and killed whol0 coll pertussis (DTwP) or ocollular po1tussls (lllnP) vacclt)
Dose, route 0.5 mL; intramuscular
Site Anterolateral aspect of mid-thigh (gluteal region: scintic nerve injury; inndequate rcspo 11 ~l')
Schedule
National program DTwP at 6, 10 and 14 weeks (primnl'y); at '15-18 mo11ths nnd 5 ycnrs (boosters)
IAP 2016 (see footnote) DTwP for primary and DTaP or DTwP for booster in schedule ns nbovc; Tdnp/Td nl t(l-12
years; Td every 10 years
. Catch up (IAP 2016) <7 years: DTwP (preferred) or DTaP at 0, l and 6 months
' . ' 7- 10 years: Tdap at 0 month; Td at 1 and 6 months
.·Adverse reactions >11 years: One dose of Tdap; one dose of Td every 10 years
Common: Local pain, swelling, fever (DTwl»DTnP)
Rare: Hypotonic hyporesponsive episodes, inconsolable cry; fever >40S'C; se\.'. ll ft':;;
encephalopathy (DTwP=DTaP)
Contraindications (i) Progressive neurological disease (administer DT or dT instend); (ii) nnnphylnxis nfter X t:' j,111s
•• \" ,_. !.' ....
dose; (iii) encephalopathy within 7 dnys of previous dose · !
Preca11tions: Previous dose associated with (i) fever >40.5°C within 48 llo ' , (") ,, tc-
. ep1so
· d e <48hours; ("') 11 11YP0 1 11
hyporespons1ve 111 pcrs It
s en ti neons{) Inble crying for >urs,
hours, <-lHhiiur:i;
. '_(
(iv) seizures <72 hours
3
' Storage
- ...... 2-8°C; sensitive to light ·
IAP recommmendalions:
DTwP should be used in primary immunization; DTaP vaccine should be used only In childl'l'll with scvl'l'C odvt•rsc effects nftcr prevlou~ ,i.r-t' i•f
DTwP or children with neurologic disorders; Either DTwP or DTn,P may b~ used for booster clo~c~; DTor used should hove C':J or morn pri t u~-1~
components; Tdap should not replace the second booster of DTwl or DTal
lmmunlzntlon ond lmmunodoflcloncy 191 -
---
d evelopment of \'adous t)'pes ~,f pmlfkl\ ,,celluhu·
pertussis Yacdncs, or DTnf'. Tlwsl~ \' l\~dnes conlnln
vncdnes In lndh\ contnin 5 Lf of tetanus t?xoid, 2 Lf of
dlphthel'in toxoiu nnd three ncellulnr pertussis cor:n~onents
(perlu::isis toxoid 8 pg, filnm~nt~us .hcmagglutimn 8 µg
inactivntcd pertussis tnxin .mct 1._)t\l' lll' nHH'c 1\1.h.llllnnnl
pertu!'tjs antigens, like Hlnment(l\IS hem1\~~lutinin (\'HA), nnd }Jl'l'h\din 2.5 pg). Contr<11nd1cat1ons to Tdap are the
pertactin. fimbri,1\ protl'in nnd n tHmfimhrinl protdn. same ns those listed for DT<iP or DTwP. Tdap may nlso be
Approved \'<\ccines hn\'~ nt h•ast thn.~0 pnthng0nk used llil replacement for Td/tetanus toxoid (TT) booster
pertussis antigens, at least ·l lU <'f inncth·nted pertussis In children tlbovc 10 yenrs and adults of any age, if they
toxin and 6.7-25 Lf of DT. \Vhill' thl' dtkncy of these hnve not received Tdap in the pnst and 5 yea~s have
\'accines is similar to DTw r , the risk llf S\'Stemic nnd locul dnpsed since the receipt of previous TI /Td vaccme.
side effects is lower. Tht:- DTnP \'(Kdn0 ls not induded in
the National Program due to its pN.,hihitivl.' Cl) 't, The li\P Tetanus Vaccine
previously recommended that tlw \'4'l'1.:ine be offored to Extensive routim:' immunization of pregnant women has
all children who can afford. in \'il'W ,,f the ndv,mtngu of led lo decline in the incidence of neonatal tetanus.
fewer side effects, or following '"' nd\'erse 1.•ffoct with Immunizing pregnant women with two doses, wi~h the
DTwP. Since recent studies su~~est th,\t the dficm:y of second dose administered at least 4 weeks pnor to
DTaP vaccines, when used for primary inununi:r.ation, is delivery, provides passive immunity to. the baby due ~o
lower (-16-92%) than with DTwP (6 l-.'l1J%) p.wticullnrly the transplacentnl passage oflgG antibodies. Tetanus .toxm
for perfussis, the IAP thus recommends that nnly DTwP is inactivnted by formalin and adsorbed onto aluminum
(and not DTaP) be used for primary inummization. salts lo cnh,mcc immunogenicity. Each dose of the vaccine
Boosters at 16-2-l months and at 5 years mny be with either contnins 5 Lf of toxoid. The vaccine is heat stable and
DTwP or DTaP (Box 10.5). Contraindications for DTaP remains potent for a few weeks even at 37°C. The efficacy
vaccine are similar and the vaccine should not be given, if of TT vaccine varies between 80 and 100%. While antitoxin
a previous dose of DTwP or DTaP was associated with a Jew! of l),01 lU/mL is considered protective, the level of
contraindication; these children should complete protection available also depends on the toxin load. Since
immunization with DT instead of DTwP or DTaP. tetanus may occur at any age, primary immunization
should begin in early infancy. Tetanus toxoid is given with
Reduced Antigen Ace/lular Pertussis Vaccine (T"dap} DT and pertussis vaccine in DTP. DT, Td and TT may be
and Reduced Antigen Diphtheria used as boosters nt 10 and 16 years of age and for wound
Toxold Vaccine (Td} prophylaxis (Table 10.8). Children who have not received
As natural immunity to diphtheria and pertussis is primary immunization, should receive 2 doses of TT
I
acquired through apparent or inapparent infections 1 month apart.
(Chapter 11), a large proportion of adults especially in
developed countries, are susceptible through lnck of Measles-containing Vaccines
natural boosting and waning of immunity. In nonendemic Measles vaccine, derived from the Edmonston-Zagreb
countries, revaccination against diphtherin every 10 years strain, is available as a monovalent preparation, or in
may be necessary to sustain immunity among adults, combination with rubella (MR), mumps (MMR) and
particularly healthcare workers. Vaccines useful in such varicella (tvlMR-V). Both cellular and humoral responses
situations include diphtheria and tetanus toxoids (DT) and · are elicited. Since infants arc protected by m a ternal
combinations with reduced toxoid content (Td, Tdap). antibodies till 6-9 months of age, administering the
While standard dose DT is recommended for primary vaccine at 9 months in endemic countries balances the
immunization against diphtheria because of its superior need for early protection with the ability to ensure
immunogenicity and minimal reactogenicity, the seroconversion. However, interference b y maternal
reactogenicity of the vaccine increases with age. If given nntibodies cnuses primary vaccine failure in 15%, making
beyond 7 years of age, primary immunization or booster a second dose necessary at 15 1nonths. During outbreaks,
doses should be in the form of Tdap or Td, which contain the vaccine muy be given even earlier (-6 months) w ith a
smaller amounts of diphtheria toxoid (2 Lf) and acellular repeat dose at 12-15 months. Each vaccine dose contains
pertussis vaccine than DTP, and is adequately immuno- at least 1000 infective units of the attenuated virus. Measles
genic even in adults. To promote immunity against vaccine loses potency rapidly after reconstitution; unused
diphtheria, this vaccine may be used whenever TT is vaccine should be discarded after 4-6 hours since
indicated in children above 7 years of age. contamination muy lend to staphylococcal sepsis and toxic
Similarly, Tdap offers the prospect of reducing pertussis shock syndrome.
incidence in adults and adolescents, and also reduces the The two doses of measles vaccine at 9- 12 and 15-24
risk of their transmitting disease to young children. Its months (Box 10.6) in the national immunization progr;tm
reduced antigen content causes less severe adverse effects are being replaced by the MR vnccine in a phased manner.
while being sufficient to induce protective response in This follows the nationwide 'me,,sles rubella' program
previously immunized (booster effect). The available Tdap (launched February 2017) in which one dose of the vacdn~
-
I
192
~:;:--;;;;--;;--;::::::~~-~~:----~~~~,~~~-:'""~~,_,.-----·~~~~~~~---
Table 10.8 Tetanus prophylaxis following wound
All other wounds
No
-
No**
Gi\-e tetanus toxoid (TT) ii more than •10 years or u5 years have elap>ed since last dose
incorporating a birth dose of the vaccine can be used. If is now part of the Universal Immunization Program,
HBIG is not administered, the baby should be immunized introduced as a pentavalent vaccine (DTP, HBV and
in an accelerated schedule at 0, 1 and 2 months, and an HibPRP-T vaccines) in 2015.
additional dose at 9-12 months. Combined passive and
active immunization with use of HBIG and HBV vaccine Pneumococcal Vaccine
results in 90% reduced risk of HBV transmission in S. pneumoniae causes 15-50% of community-acquired
m
patients with needle stick injuries, sexual exposure or use pneumonia, 30-50% of acute otitis media and 50% of
of blood product not screened for HBV. deaths due to pneumonia. Pneumococcal pneumonia is
Seroconversion rates exceed 95% after three HBV doses:
Antibody titer >10 mlU/mL is protective. Vaccination
usually induces long-term immunity, and booster doses
the leading single cause of vaccine-preventable deaths,
globally and in India. Twenty of 90 known serotypes
account for 80% of invasive pneumococcal disease, and 13
I
are not routinely recommended. Double dose of vaccine serotypes cause 75% of invasive disease in young children.
and boosters may be required in patients with chronic Children below two years of age are particularly
kidney disease or immunodeficiency, in whom titers may susceptible to invasive pneumococcal disease. Children
wane. at high risk of disease, regardless of age, include: (i)
primary immunodeficiency, HIV, immunosuppressive
Hemophilus Vaccine therapy and organ transplant recipients; (ii) sickle cell
Haemopltilus i11.fl11enzae b (Hib) causes invasive infections disease, asplenia or hyposplenia; (iii) chronic cardiac, liver
such as pneumonia, meningitis and bacteremia, especially or pulmonary disease; (iv) chronic kidney disease and
in children <2-year-old. Vaccination prevents 33% of nephrotic syndrome; (v) d iabetes mellitus; and (vz) children
pneumonia and 90% meningitis related to Hib. The chief with cerebrospinal fistula or cochlear implants.
antigen is Hib capsular polysaccharide, polyribosylribitol Two kinds of vaccines are available. Unconjugated
phosphate (PRP), which is conjugated to tetanus toxoid polysaccharide vaccine h as 25 µg capsular polysaccharide
(PRP-T), mutant diphtheria toxin CRM-197 (Hib-OC) or of each of the 23 serotypes termed PPV23. Since
meningococcal outer membrane protein (PRP-OMP). Both polysaccharides stimulate B cells independent of T cells,
monovalent and combination (with DTP and hepatitis B the vaccine is poorly immunogenic <2 years and
or IPV) vaccines are safe and immunogenic, with efficacy immunological memory is low. This vaccine does not
of 85-95%. The vaccination schedule depends on age of reduce nasopharyngeal pneumococcal carriage or provide
the child at immunization (Box 10.8). A booster is required herd immunity. Its efficacy in preventing invasive
in the second year to sustain protection. As Hib infections pneumococcal disease in high-risk categories is <70%;
chiefly affect preschool children, IAP recommends that more than 2 doses are not recommended.
the vaccine be given to all children up to the age of 5 years; The pneumococcal conjugate vaccine has the
older children need vaccination, only if planned for polysaccharide of 13 most commonly pathogenic serotypes
splenectomy or if having sickle cell disease. Hib vaccine linked to a diphtheria carrier protein (PCV13); another is
11 194 ~~~~~~~~~~--=~~~~~~~~~--------~~~~-----...
Essential Pediatrics
a 10-valent conjugate vaccine (PCVlO) combined with non- on G9Pll or 116E strain, manufactured_ in Ii:dia. The
typeable H. inj711enzne vaccine. Apart from robust immune vaccine has 49-54% efficacy against r~taviral diarrhea in
response and immunological memory, conjugated the first 2 years of life; it is inexpensive and safe '";th a
vaccines reduce nasopharyngeal bacterial carriage low risk of intussusception. . .
resulting in significant herd effect. The protective efficacy All three rotavirus vaccines may be ~ven \\'1th OPV
is 95-99% for invasive pneumococcal disease covered by without compromising efficacy of either \~~ccine.
included serotypes. Vaccination is avoided during acute gastroententis, as it
Since pneumococcal infections cause significant might compromise vaccine _take. Whil~ none o_f t~e
morbidity and mortality in children <2 years of age, IAP vaccines increases the risk of mtussusception, caution IS
recommends using the conjugate vaccine (Box 10.9). Since necessary in infants at ~k of ~tussusception, e.g: thase
the risk of invasive infections decreases with age, with chronic gastrointestinal disease and gut malforma-
vaccination beyond 5 years is not necessary except in high- tions. Immunization should be completed by 8 months of
risk categories; the latter should additionally receive the age. Studies suggest that vaccine efficacy may be ~~wer in
polysaccharide vaccine. An additional dose of the vaccine countries with high infection rates and competi~on for
may be given in high-risk categories 3-5 years later. Given intestinal infection by other pathogens. The vaccine has
its public health importance, pneumococcal vaccination reasonable potential for preventing diarrhea related
was launched in three states in May 2017. Vaccination will morbidity and mortality in de.vel~ping co~tries. Gh·~
be extended to the entire country in a phased manner. its importance, rotavirus vaconation was introduced m
the UIP in 2016 in selected districts in four states (Andhra
Rotavlrus Vaccine Pradesh, Himachal Pradesh, Haryana and Odisha) using
Rotavirus is the chief cause of diarrhea in infants and the Rotavac vaccine.
toddlers, accounting for 6-45% of diarrhea-related
hospitalization in Indian children. Natural infection does Human Paplllomavirus (HPV) Vaccine
not protect against reinfection or severe disease. The first Cervical cancer, the second most common cancer in
licensed vaccine (Rotashield), a live oral tetravalent women, is almost always due to infection with oncogenic
vaccine, was withdrawn following an association with HPV belonging to 20of100 known serotypes. Serotypes
intussusception. Two live-attenuated oral vaccines are 16 and 18 cause majority of invasive cervical cancer;
currently used worldwide (Box 10.10). Rotarix is a oncogenic serotypes also cause anal, vulvar, Yaginal,
monovalent vaccine containing at least 106 median cell penile and oropharyngeal cancer. Nononcogenic serotypes
culture infective doses of rotavirus strain G1P8 attenuated 6 and 11 cause 90% of anogenital warts.
in Vero cell culture. RotaTeq is a pentavalent vaccine with HPV vaccines contain self-assembling virus like
2-116 million infectious units each of the 5 strains [Gl-4 particles containing recombinant Ll, a major capsid
and PS] reassorted between bovine and human WC3 protein. These vaccines protect against 90% of infections
rotaviruses, and attenuated by Vero cell culture. Both with included serotypes, but do not provide cross
vaccines have 85-98% efficacy against severe rotaviral protection against other strains. The quadrivalent vaccine
gastroenteritis. Rotavac is an indigenous monovalent Gardasil (HPV4) protects against strains 6, 11, 16 and 18,
human-bovine recombinant live-attenuated vaccine based while bivalent Cervarix (HPV2) targets HPV 16 and l S.
1
Type , Pnewnococcal conjugate (PCV13.. PCV10j Pneumococcal polysaccJ111ride (PPV2Jl
Dose, route 0.5 mL; intramuscular 0.5 mL; intramuscular or subcutanc,' •JS
Site Anterolateral thigh or deltoid Deltoid
Schedule .
National program Some states: Three doses at 6 weeks, 14 weeks and 9 months Not recommended
, IAP 2016 Three doses after :;::6 weeks age; given 2::4 weeks apart; High-risk category•; One dose ~8 we;-~
one booster at 15- 18 months after primary course with conjugate
Catch up At 7-11 months: Two doses >4 weeks apart; vaccine; repeat 5 years later, if risk
one booster at 15-18 months persists
.,..
I
At 12- 23 months: Two doses >8 weeks apart
At 24-59 months: One dose
IAdverse reactions >60 months· One dose, if high risk*
Fever, local pain, soreness, malaise Pain, redness
Contraindication. Anaphylaxis after previous dose
'.Storage 2-8°Ci do not freeze 2-8°C
•for details, see tex(above· ·-
hnmunl1Atlon 1111cl lnu;.;..n:.;,;11;.;.;n.;,;,o.:.
cJo;;:.;f:.;,;lo;.:.l,;.:
tm~o~y~----------- j 195 -
--
0011 10,'IO: nrul 11 Jf11vlt1 Jtj w J1,Ut11HJ
- - -- ~ - -
Rntnl'/,\' (RV1) Uo/11'/'1111(1' Vl1) JM11vac:
1 ml. (lyophl\1:1.1Kl)l ?. 111L (lfttuld) t; dflJplj
I.~ ml .. Olquhl)
Scl1erl111tl
.
; Nnlioni\l progrnm 9cfcctctl &f<Hc!l: 3 dose!! at 6, 10 and
·14 W!!eks~
IAP 2016 2 dnstHI nl '\ l) llml I il Wl'l'l<rt 3 dntieti 111 (), IO rtnd '14 wcck!i' 3 tluseit <tl 6, 10 and 14 weeks
(prvforn•d In ti n111 I l ll wt1111\t1)~
Adtierst' renctin11s £lover, dlorrlwn, vomlllnv,; ll1llu111w1ceplfo11 ftt rilru
Co11troi11rllct111011 PaRt hiHtory of lnt11Hti111:1n•pllo11; ~uvcnJ h11111u11odoflcle11cy
Prt'c1111tio11 Postponu vni:dnl\tlon dlll'lllf-1 llllf'IOlllM dlnrrhc11or1t1oduralc llJ11ca11
Stor11gr. 2.-8 9 C; protect from hl'ill; lltll.l wllhln 4 hr of r·cc1111rllllutlon or opct1lttg
•Adminlst~r :<:.I \\'('t'k!I i\l'<\l'I lw~hmln~ 111?:ti \Vl'"l..ri 11[ ''II'' (:~Ill wr•p~.~ f11r l<olof'I><); t'11111pll'tl11y, IJy ll rmmllt!> uf il~C
Both vaccines prevent ccrvlcnl ilr :1//11 1wnpl11r-illl 81'11du 2 Box 1o,11: Human paplllomavirus vaccine
and 3, nnd nctcnocnrclnomn i11:iif11. C.nrd11r·ill 11IH1l pl'llVl'lllll
serolype-rclntcd HCnitnl wnrls nnd vnp,lnnl 11nd v11lv111· IJ011e, ro11111 0.5 mL, lntramuscular
intrnepithelinl ncoplnsln. Both vn1:cl1wM111·1 1110nl 1 Siii! Upper a rm (deltoid)
immunogenic nt 9-1·~ y 'nrs of lltW ond prol1•dhlll p1!l'Hlt1lfl Sdwdttlc!
for at lenst 5 ycnrs. The hlL'lll l1P,L' n l v1H:1.: l1111tlo11 nnd ncl.!d National program In fiornc sl<1tes: Two doses 6--12 months
of booster doses, If nny, is not dcll'l'lllhwd. opilrl in girls 11-13 years
WHO; JAi' 2016 Clrl119-14 years old: 2 doses of HPV4;
Governments of Delhi nnd Punjnb h1wL1lnlllnlcd school· or Hf'V2 ~6 months apart
based progrnms for Hirls aged l 1-1~ Yl'llnl old Hl11c1i 20l6. Girls <::15 years, immunocompromised:
Elsewhere, lAP recommends thnt the vn\'.dnc Ahould be 3 dose& [HPV4: 0, 2 and 6 months; or
offered to nil girls prior lo sex uni dl but (Box 10.'l'I ). 1
Hl'V2: 0, 1 and 6 months)
Immunization cnniLlS lhe risk of compliwcncy rcgnrdlnM Cntch up Up to 45 years (IAP); preferably before
routine screening for cnncc1·; which together with iniliillion of sexual activity
incomplete immunizntion covcrnge might pnniduxlcally
raise cervical cnncer-rdntect mortnlily. There nm 110 Hcriow1
adverse events of HPV vaccine.
Adverse ret1cl/011s
Co11lraimllcnllon
Loca l p<1in, swelling, erythema; fever .
Syncope (d ue to injection, not vaccine)
Anaphylaxis after previous dose
Im
Sl ora,~e 2-8°C; protect from light
Japanese B Encephalltls Vaccine
Japanese cncephnlitis UE) is nn importnnl coul'Jc of vlrnl is highly immunogenic in children, with seroconversion
encephalitis in Tndln nnd is nssoclntcd wilh high fnln lily. >90% wilh two dose!!. The risk of adverse effects is lower
Vaccination ns n control mcnsure is recommended for nil than livc-allcnuatcd vaccine. The inactivated purified Vero
children nnd ndulls residing in highly endemic nrcns nnd cell derived vaccine (bil!lcd on Kolar strain) is safe and
for individunls visiting endemic nrcns for ltlngcr thnn 4 effective, wilh scrocovcrsion in 93-98%.
weeks. Previously nvnilnble vnccinc:-i, dlsconllnueu in
2005, Included innctivnted mouse brain-dcl'lvcJ vnccine Typhoid Vaccine
(Naknynmn or l3cijing-l strnins) nnd prlmnry hnrnsler Typhoid vaccine is currently not part of the national
kidney cell culture vnccinc (Bcijlng-3 strain). Three of lhe progrnm, but is recommended by IAP for families who
four second gencrntion vnccincs ore licensed for use In Ind in con afford (13ox 10.13). The whole cell-inactivated typhoid
(Box 10.12). vaccine containing hcilt-kill cd phenol-preserved or
The Jive-nttcnuntcd cell cullurc vnccinc is used in lhe acclonc-innclivated whole cell S. typl1i and S. paratyphi A
nntionnl prngrnm in hypcrcndcmlc dlslrlcts of Ullnr nnc\ D iH no longer used. Two doses of the vaccine,
Pradesh, West Bcngnl, Assnm nnd Knnmlnkn. It IH b<rncd odmini s lercd SC 4 weeks apart, induced humoral
on SA-14-'14·2, n p;cncticnlly stnblc ncuro-nlten11all.~d JE nntibodic8 that were 50-80'Y., effective in preventing
strnin thnt is unlikely to show ncurovlnilL~tH'l' (Box 'I0.12). typhoid. AcJvenic effcct1:1 (chiefly fever, local pain and
While n slnHlc dose hns prntcclive dficncy of H!l-99%, two hencJoche) were common (10-35'%) and rcvaccination was
doses nrc recommended Lo provide compll'lc nnd HUH\nlncd required every 2-3 years.
protection. In cntfornlc districts, n strnlcgy of mnHH An oral. vnccinc, not marketed in India, contains 2-6
itnmunlznllon followed by roullnc vllccl nnllon ls pl'lldlscd. million llvc·nl\cnunlcd lyophili zcd bacteria of Ty21a
The purified formnlln lnnctlvntl!d SA·'ltl· I11·2 IH n whoh! mulnnt slrnin of S. typl1i. The mutation is genetically stable
virus vncclnu derived from Vero cell c11lllll'c, The vncd nc nnd unlikely to revert lo virulent form. The vaccine is
196 Eaaentlal Pediatric•
~uppliect as an enteric coated capsule that induces coupled to diphtheria toxoid or itHmutant toxin CRM1'17
intestinal mucosal immunity, with an efficacy of 50-60% are not licensed in India . Conj ugnte vnccinc't arc preferred
within 7 days of completing the schedule. To avoid to polysaccharide vaccine, since they generate 'ltrong
bacterial inactivation b y gastric acidity, capsules are anamnestic response and show prolonged immunological
:;wallowed intact, making the vaccine unsuitable for young m emory.
children. Antibiotics are avoided for 3 days before to
7 days Clfte r vaccination to avoid interference with Varlcella Vaccine
r~sponse . Vaccination is repeated every 3 years. Varicella is a benign self-limiting illness, but cornplic;:ition.:s
The Vi capsular polysaccharide vaccine contains the are common in adults and in immunocompromised
purified Vi capsular antigen of S. typl1i strain Ty2. Children patients. Each dose of varicclla v<tccinc hns .1t ll•J<;t 1000
older than 2 years, adminis tered one vaccine dose, develop plaque-forming units of the live virus of Ob <; tr,1in
anti-Vi IgG antibodies with protective efficacy of 50-75%. attenuated in human diploid cell culture. Both cellul.1r Jnd
Since polysaccharide vaccines lack memory responses, humoral immune responses arc cl icilc!d , providing 9,_ 99"~
revaccirmtion is essential every 3 years (Box 10.1~). T~o
I
protective efficacy. Following onedosL', seroconn~ r~i n n is
typhoid conjugate vaccines are approved for use m India seen in 95'Yo young children and 80'X, uf tlun .• > 12 ye.1rs;
and recommended by IAP for children >9 months old. two doses seroconvcrt 90% of the latter. If brl•.tkthro u •h
Here, the Vi antigen is coupled to a carrie r protein such infection occurs, it is us ually a mild Jfobrilc illnl'S w ith J
as tetanus toxoid (PedaTyph®and Typbar-TCV®); vaccines few lesions and predominance of papulcs over vc-;iclc.;.
I
adults without history of varicella, particularly in
institutional settings (school, hospital or army). When
recommended for post-exposure prophylaxis (within Rabies Vaccine
72 hours of contact), its protective efficacy is -70%. India is endemic for rabies, accounting for 50% of global
deaths. N erve tissue vaccines are not reconunended due
Influenza Vaccine to poor efficacy and high incidence of adverse effects.
Influenza virus has three antigenic types (A to C) and Tissue/ c~ll culture vaccines are available as lyophilized
several subtypes based on the surface antigens preparations that are reconstituted to provide at least 2.5
hemagglutinin, and neuraminidase. Mutations due to IU per intramuscular dose, and include: (I) Purified duck
antigenic drifts and shifts result in frequent changes in embryo vaccine (Vaxirab); (ii) purified chick embryo cell
circulating strains. Influenza viruses (A, B) cause global vaccine (Rabipur, Vaxirab-N); (iii) human diploid cell
flu epidemics with severe disease in young children, the vaccine (Rabivax); and (iv) purified Vero cell vaccine
(Indirab, Verorab, Abhayrab, Verovax-R). These vaccines remaining immunoglobulin Is odminlAtcrcd Intra·
have comparable efficacy and, since they lack myelin basic musculnrly at n site nwny from vncclnnllon sill', 11.'Htnlly
protein, are relatively safe. the deltoid or nnlcrolnlernl thigh. Locnl tenderness nm!
stiffness nnd fever arc common. Currentl y nvailnblc t•qulnc
Post-exposure prop11ylaxis: An animal bite/wound is
immunoglobulins arc potent aml ovcrnll 1-1nfo, but ildvcrsc
characterized as follows: Category I: Animal touch or lick
effects arc common nnd usually require prior skin ll•i<Ii"K·
on intact skin; Category II: Minor scratches or abrasions
While preferred, humon immunoglobulin is expensive
without bleeding, licks on broken skin or nibbling of
nnd not available rc11dily.
I
uncovered skin; and Category III: Single or multiple
Vnccin11lion is usu11lly plmrncd mi in!; the Essc•11 or WI 10
transdermal bites, abrasions that bleed, scratches or
contamination of mucous membranes with saliva/licks. sclied111C', in which 5 doses arc given on dnys 0, 3, 7, -1.1i1nd
28; an i1dditionnl dose on dny 90 is ndvist•d in irnmu no·
Individuals with category II or III wounds need wound
compromised or severely malnourished indiviJuills. The
management and rabies vaccine (Box 10.16). ~atients '.""ith
wound category III, and imrnunocomprom1sed patients Updated Thai Red Cross Schedule involves ndministering
with wound category II, should also receive rabies two intrndcrmnl doses cnch on days 0, 3, 7 and '. HJ.
imrnunoglobulin. Patients who have received pre- or post- Abbreviated and effective nlternatc schedules incl 11 d1~:
exposure prophylaxis with rabies vaccine in tlze past do not Zagreb (two JM doses on day O; one dose cnch on d.1y1. 7
require immunoglobulin. and 14); abbrevinted multisite (similnr lo Z11grcb, l'xn ·pt
that last dose is on day 21), reduced four dose (IM do .c
Wound management includes immediate irrigation
on 0, 3, 7 nnd ]4 d11ys), nncl eight site (8 intrndcrmnl do:,•·'l
with running water for 10 minutes, thorough cleaning with
soap and water, and application of povidone iodine, 70% on day 0, four doses on day 7, nnd one each on <fay 28 .11HI
alcohol or tincture iodine. Tetanus toxoid and antibiotics 90). Following re-exposure, patients who have prcviow.ly
are administered as indicated. Wound suturing is completed pre-exposure prophylaxis should rece ive~ lw o
doses on days 0 and 3.
avoided; if necessary, it is performed after administering
imrnunoglobulin. Pre-exposure propliylaxis: This is offered to individ u.il"
Rabies immunoglobulin provides passive immunity by at high risk of rabies, such as laborntory staff handl ing
neutralizing rabies viruses; dose is 20 U /kg for human virus or infected material, care providers to patients w it h
immunoglobulin (ImogenRab, KamRab, BeriRab-P; rabies, veterinarians, animal handlers and catche r",
maximum 1500 U) and 40 U/kg for equine preparations taxidermists, wildlife workers, wardens, qunrnnt i11 c
(anti-rabies serum, Equirab, Vinrig; maximum 3000 U). officers, municipal workers, postmen and travele rs to
This is infiltrated in and around the wound as soon as endemic areas. Three JM doses nrc given on days 0, 7
possible and not later than day 7 of injury. For large or and 21or28. A booster dose is required ofter 1-yr ,\tld
multiple wounds, immunoglobulin is diluted with normal every 5 years thereafter; boosters arc required annuillly,
saline to infiltrate the entire wounded region. Any if using the intradermal schedule. Antibody titers nrL'
Immunization and Immunodeficiency 199 .
monitored 6-12 monthly and boosters given to maintain titer administration to all children. High-risk categories in
>0.5 U/mL. which vaccination must be considered include: (i) patients
with chronic liver disease; (ii) seronegative travelers to
Hepatitis A Vaccine endemic areas; (iii) children attending crcches and
India is endemic for hepatitis A; 50% children are daycare; (iv) seronegative adolescents; and (v) liver and
seropositive by 5 years of age, following infection usually kidney transplant recipients. The vaccine is effective as
with minor manifestations. Disease severity, complications postexposure prophylaxis, if administered to tmimrnunized
and mortality arc higher in adolescents, adults and household or institutional contacts of symptomatic
children with underlying chronic liver disease. Two types patients within 10 days of exposure.
of vaccines are available. Formalin inactivated viral
vaccines usually have aluminium hydroxide or a virosome Meningococcal Vaccine
adjuvant. The vaccine is available either singly or in Neisseria meningitidis accounts for 30-40% cases of
combination with hepatitis B. Two doses, administered bacterial meningitis in children, with high case fatality.
6-12 months npart, provide protective efficacy of 95%, if
administered at >1 year age; maternal antibody may
interfere with immune responses in infancy (Box 10.17).
Two live vaccines are based on H2 and L-A-1 strains of
hepatitis A virus, attenuated through repeated cell culture
Invasive infections are caused by serogroups A, B, C, Y
and W135. While serogroup A (and sometimes C) cause
epidemics, endemic disease in India is due to sero-group
B. Two types of vaccines are available. Unconjugated
vaccines contain group specific capsular polysaccharides,
I
and grown on human diploid lung fibroblasts. A single which are T cell independent, do not induce immuno-
dose of the vaccine is immunogenic and safe (Box 10.17). logical memory and are poorly immunogenic below 2 years
While hepatitis A vaccination is not a public health of age. These are available as bivalent (containing groups
priority, improving hygiene has resulted in increaseded A and C) and tetravalent (groups A, C, Y and Wl35)
age at infection, and serious infections including fulminant vaccines. Conjugate vaccines are preferred o v er
hepatic failure may occur. Hence, IAP recommends its polysaccharide vaccines due to higher immunogenicity,
1Table 10.~: Combination vaccines for use in childre,;and infants ii. Distraction techniques (playing music, pretending to
blow away the pain, deep breathing)
·vaccine Ex~mples -
ill. Breastfeeding or ingestion of sweet liquids during
oTwP-HB-Hib Pentavalent vaccine; Pentavac PFS®,
vaccination
Comvac-5®, ComBE Five®, Shan-5®
iv. Stroking skin near injection site
May combine in same syringe, e.g. Qvac®
+ HibPro®, Hiberix® + Tritanrix® v. Administering IM injections rapidly without
oTwP Tripvac®, Triple antigen®, Comvac31Ri aspiration; and
DTaP-HB-Hib Easy-5® iv. Topical analgesia (5% lidocaine or prilocaine emulsion
DTaP-Hib-IPV Pentaxim® or spray).
oTaP lnfanrix®, Boostrix®, Tripacel® Older children are less anxious, if the procedure is
Tdap Boostrix®, Adacel® explained, and by vaccinating in sitting rather than lying
OTwP-HB Shantetra®, Q-VAC®, Tritanrix-HB®, down position.
Tripvac-HB®, Comvac-4-HB® Immediate allergic reactions are rare and difficult to
DTaP-Hib May combine Tripacel®+ ActHib®, lnfanrix® predict. Severe reactions (anaphylaxis) are usually caus.e d
+ Hiberix® by vaccine constituents, rather than by microbial
DTwP-Hib Easy-4®, Quadrovax®, Shan-41Ri, Tetract contamination. While anaphylaxis is rare (1 per million
Hib®; Triple antigen® + HibPro® doses) and may follow any vaccination, yellow fever,
HepA-HepB Twinrix® MMR and tetanus vaccines are most commonly
MMR-V Priorix tetra®, Proquad® implicated. Each patient must be observed for at least 15
Meningococcal A, C, Y and 135 (Mencevax AC~; A, minutes after vaccination. Anaphylaxis might need to be
C, Y and 135 OT conjugate (Menactra®) differentiated from vasovagal reaction . Components
Pneumococcal 10 or 13-valent (Prevnar®l, 23-valent implicated in allergic reactions include:
(Pneumo231Ril, polyvalent polysaccharide
i. Egg protein: Yellow fever, measles, MMR, rabies PCEV,
(Pneumovax®)
influenza (killed injectable and live-attenuated)
aP: Acellular pertussis; ap: Acellular pertussis reduced dose; D/DT:
diphtheria toxoid; d/dT: Diphtheria toxoid reduced dose; HB: Hepatitis B;
vaccines
HepA: Hepatitis A; Hib: Haemophilus influenzae b; MMR: Measles, ii. Gelatin: Influenza, measles, MMR, rabies, varicella,
mumps, rubella; TITT: Tetanus toxoid; V: Varicella; wP: Whole cell pertussis yellow fever and zoster vaccines
I
(horse) immunized
Rabies antiserum Bite by potentially rabid animal 40 IU/kg
Lapsed immu11i=atio11: Table 10.12 suggests schedules for • CDC The Pink Book. https://www.cdc.gov/vaccines/ pubs/
children who have missed routine immunization. For pinkbook/ index.html
vaccines ·with multiple doses, the entire schedule need not • GOI. Immunization Handbook for Medical Officers. New Delhi:
be repeated and only limited doses are given. The vaccination Department of Health and Family WeUare; 2016
schedule for adolescents is discussed in Chapter 5. • Guide to introducing Inactivated Poliomyelitis Vaccine b.lSed on
the Polio Eradication & Endgame Strategic Plan 2013-2018.
Passive Immunization Available at http://www.who.int/immunization/diseases/
Passive immunity is resistance based on antibodies, poliomyelitis I endgame_objective2/ inactivated_polio_va: cine/
preformed in another host. Thus, preformed antibodies to • Indian Academy of Pediatrics, Advisory Committee on · raccines
varicella and hepatitis B can be injected during the and Immunization Practices (ACVIP) . IAP recom mended
incubation period to limit viral multiplication (Table 10.13). immunization schedule for children aged Othrough 18 ye.'r~, 20l6,
Normal human immunoglobulin serves the same purpose, and updates on immunization. Available at http://\\'l-l.''W.ac\riP·
if specific immunoglobulin is not available, e.g. to protect org/files/IAP-immunization-schedule-2016-IP-2016-Ept!b.pdf
from hepatitis A or measles. • Mission Indradhanush. Available at http://www .mission
indradhanush.in/
SUggested Reading • National Inununization Schedule for infants, children and pregnant
• AAP Red Book.. AYailable at www.aapredbook. aappublications. women. Available at https:/ /mohfw.gov.in/sites/default/ fueSI
org/siteI resources 245453521061489663873.pdf
11
Infections and Infestations
Tanu Singhal • Rakesh Lodha • S~shil_ K ~a~ra
significant is unknown. However, fever may be associated visits. The overwhelming mnjority nrc due to ~lrt1J
with adverse effects such as paradoxical suppression of .m fcctions.
. . Of grcn , 1er concern nrc fevers without
ti locnh1.lno
( ,.,
immune response, increased insensible water losses, sh~ns/without focus in children below te ng.c . '3 yc.1 rs
0
I children.
Heat illness is a medical emergency. The high
temperatures can cause irreversible organ damage and
should be brought down quickly. Since the hypothalamic
set point is not altered, non-steroidal anti-inflammatory
controversial. If fever is thought to be due to over bundling
then repent temperature assessment should be done ;ifter
15-30 minutes. Most guidelines recommend hospitnh1J-
tion of well looking febrile infants less than I month of
age as tl'\ey may have serious infections. These infants
drugs, which act by reducing prostaglandin production,
are ineffective. External cooling is needed v.rith ice water Fever >3B"C In less than 90 days age no focus
sponging, cooling blankets, cold water enemas and gastric I .
washes. At the same time, measures should be taken to
correct the underlying condition.
t
l Well looking]
t
Sick look§ ]
I
antibiotics. A well-looking infant with no chrucal focus of of FUO remains undiagnosed in 10-20% of the cases.
infection and a negative screen (leukocyte count <15,000/
cu mm band count <20%, C-reactive protein negative, Approach to FUO
urine ~hite cells <10/HPF) can be observed at h.ome
without antibiotics, provided the care takers are reliable The first step is to identify sick patients who need
and agree to bring the infant for reassessment 24 hours stabilization and urgent referral to a tertiary care centre.
All attempts are made to reach an etiologic diagnosis. A
and 48 hours later. detailed history is important, and includes:
Fever without Focus in Children Aged 3-36 Months • Whether and how fever was documented
The ns . k f seri·ous bacterial infections decreases with
o . . 01 A h'ld :'I ... -Table~1'i1: Causes of fever. of unknown origin
advancing age and in this age group it is 5 io. c i
.
presenting wi .th fever without focus should be assessed
. . Infectious causes
1 1 D tailed history is taken about vaccination, Enteric fever, malaria, urinary tract infections, tuberculosis,
compete Y· e d th d 'f f th
histo of sick contacts in family an . e con i mn ? e sinusitis infectious mononucleosis, human immunodeficiency
child:hen fever is down. If the patient looks toxic~ he virus, ri~kettsial infections, hidden abscesses (liver, pelvic),
should be hospitalized and unde~go .appr_opnate mastoiditis, osteomyelitis, chronic meningitis, infective
al . d treatment In a non-toxic child with fever endocarditis, brucellosis, cytomegalovirus, toxoplasmosis,
elv uthation39:nC one can ~erely observe. In children with kala-azar
ess an ' ·'hih d
fever more than 39oc, the risk of bacterenna is g er ~ Autoimmune causes
i't is
. recommended to do a leukocyte count and examine . Systemic onset juvenile rheumatoid arthritis, Kawasaki d~sease,
f larial parasite If the leukocyte count is systemic lupus erythematosus, inflammatory bowel disease,
smear or ma . Id b t and th
>l5,000/cu mm, blood culture shou e sen. . e polyarteritis nodosa, Kikuchi disease
· d · · tered IV ceftriaxone on either an inpatient
;::~ntpt:ti::sis. A count less than 5000 I cu mm shoul_d Malignant causes
' L~ukemia, lymphoma, hemophagocytic lymphohistiocytosis
make one suspect vira · I infecti' ons, dengue and entenc
- 208
• Duration and pattern of fever (distinguish from It should be possible to make a diagnosis of the e~ology
recurrent fever) of FUO m · most cases. In a small number
. . of cases,
. 1t may
• Symptoms referable to all organ systems, weight loss not be possible to arrive at the etiologic diagnosis. In such
• History of recurrent infections, oral thrush; joint pain, cases, peno· d.1c reassessments should be done . as the
rash, photosensitivity disease may finally surface (e.g. lymphoma, systemic onset
• History of contact with tuberculosis and animals juvenile rheumatoid arthritis). Some. cases of FUO may
(brucellosis) self-resolve over time. Empirical anti.tubercular therapy
• Travel to endemic zones (kala-azar, rickettsia) with four drugs for four we~ks ~ay b~ tried, if it is ~ot
possible to arrive at an etiologic d1agnos.1 ~ after exhaustive
• Drug history particularly anticholinergics (drug fever) work up and if the patient is sick. Empmcal use of steroids
History is followed by a complete physical examination.
should be avoided.
Documentation of fever is necessary, followed by
assessment of general activity, nutritional status and vitals. Suggested Reading
A head to toe examination, after removing all clothes, is • Antoon JW, Potisek NM, Lohr JA, Pediatric fever of unknown
vital. The physical examination should be repeated on origin. Pediat Rev 2015; 36:380-91.
daily basis as new findings may emerge that provide a • Chien YL. Clinical approach to fever of unknown origin in children.
clue to the etiology. One must keep Kawasaki disease in ] Microbiol Immunol Infect 2017; 50:893-98.
mind since diagnosis before the 10th day of fever is crucial
to prevent coronary complications (Fig. 11.2). Fever with Rash
Preliminary investigations, which should be done in Fever with rash is a common problem that might signify
all patients with FUO include complete blood counts, a serious disorder (dengue hemorrhagic fever,
peripheral smear, malarial parasite, C-reactive protein, meningococcemia) or conversely a minor drug allergy.
ESR, blood culture, Widal test, chest X-ray, tuberculin test, There are a number of infectious and non-infectious causes
urinalysis and culture, liver function tests, serum of fever with rash (Table 11.2).
creatinine and abdominal ultrasound. Specialized
investigations are done, depending on clinical clues. Evaluatlon
If a diagnosis is established on the basis of the above The most important factor that helps determine the
approach, appropriate treatment should be instituted. If etiology of an exanthematous febrile illness is the nature
no diagnosis is made, clinical reassessment and further of rash. Rashes may be macular, maculopapular, vesicular,
investigations are merited. While second line investiga-
tions are being planned and executed, treatment with Table 11.2: Common exanthematous illnesses seen in children•'
intravenous ceftriaxone may be considered as enteric fever Macular! maculopapular rash
is an important cause of FUO in our country, especially in Measles, rubella, dengue, roseola infantum, erythcma
~~~:. with negative clinical and preliminary investiga- lnfectiosum, drug rash, infectious mononucle o~i s ,
I
chikungunya, HIV, adenoviral and enteroviral Infections,
Second-line investigations include HN ELISA, contrast Mycoplasma pneumoniae, secondary syphilis, brucellosis,
enhanced CT of chest and abdomen, CT of the paranasal scrub typhus, chronic hepatitis B, CMV, lupus, systemic ,IRA
sinuses, 2D echocardiogram, complement level, Diffuse erythema with peeling or desquamatlon
antinuclear antibodies and rheumatoid factors, and if Scarlet fever, Stevens-Johnson syndrome, toxic epidermolysis,
indicated bone marrow histology and cultures and tissue staphylococcal and streptococcal toxic shock syndrome,
biopsies. Other serologic tests include brucella and Kawasaki disease
Epstein-Barr virus serology and hepatitis B surface Vesicular rash
antigen. Tests that are of limited value include quantiferon
Varicella, herpes simplex, zoster, enterovlral Infections (hand·
gold and serology for M. tuberculosis. foot-and-mouth disease), papulonecrotic TB
Petechial and/or purpuric rash
Menlngococcemia, dengue hemorrhagic fever, Indian
spotted fever, gonococcemia, hemorrhagic measles and
chickenpox, cutaneous vasculitis, Henoch·Schonleln purpura
Urticaria/ rash
Scabies, cutaneous larva migrans, strongyloides, Insect bites,
pediculosis
Nodular rash
. I
Eflopothu:10r1CJ~f~
I 20 -
Measl e~ iH c;wM~d by an RNA 'liru.s bc11Jn~ng oo th€
paramy.r.ovirus family. 'Jhc viru.1> ls tran.'>mittf:.d b'f dropt~
Hpread from th(~ e-.-f:cn:tions mthe nc,,.,e and.t'.nm~: usu.any
4 day,; bd'1n: and 5 days after the ra<;h. fh.e dl'.'~~.~ 1;
highly contahiou<; with secondary attac~ rates in
susc<:ptiblc hou.c-..ehold am tacts f':',.(C€:J".:.dm~ 'X_fi-,. fr.e ~1
of entry i.c, the te">piratl)ry tract 'Nhere th1: ·11rus mulbphes
in the respiratory epithelium. Primary ·1iu.:-mfa oocur:s
rcsultin" in infocti<.m of the reticuloerufotht:lial system
followed by secondary vin.-mi.a, wh1ch results in systemk
symptoms. The incubatirm period is arourui 10 d.aj'5.
Cllnlcol Feature5
'I. The disease ls common in preschool children; infams are
protected by transplacental antibodi~, w~h dec~ine b-J
fig. 11.3: Diffuse erythematous rash In a patient With dengue 9 months (hence the rationale for vaconation at thz.s a~).
The prodromal phase ls characterized by feve:-, rhi:-..s:cr'r.ea,
nodular, urticnrial or purpuric (Table 11.2); overlap may conjunctiva I congc."Stion and a dry hacking cough- K!J?lik
occur with one etiology having varying presentations. spots, considerE:d pathognomonic of measles, c:~ on
Other factors thnt help in diagnosis arc epidemiology, the 2nd or 3rd day of the illness as grayI ·1.-hite ~ai."1.S cf
season, history of exposure, incubation period, age, sand-liJ.-..e lE:Sions with surrounding erythema OJ1?0Sit.e tr..e
vaccination status, prodromal symptoms and relation of lower second molars on the buccal muc05a. Tr.e rash
rash with fever, dis tribution and progression of rash, usually appears on the fourth day \•:ith rise in fe-:er as
involvement of mucous membranes and history of drug faint reddish macules behind the ears, along the hairlir..e
intake. Examination includes nature of the rash and and on the posterior aspects of the cheeks ffig. 11.4). Tr..::
distribution, involvement of palms and soles (dengue, rash rapidly becomes maculopapular and sprezds to me
Fig. 11.3; spotted fever; Kawasaki disease; Stevens-Johnson face, the neck, chest, arms, trunk, thighs and leg5 b that
syndrome), involvement of mucous membranes, adeno- order over the next 2-3 days. It then starts fading in the
pathy, organomegaly and signs of meningeal irritation. same order that it appeared, and leaving behind branny
Investigations that assist in diagnosis include complete desquamation and brownish discoloration that fades o;·e:-
blood counts, C-reactive protein, blood cultures and the next 10 days.
serology, and sometimes biopsy. Modified measles seen in partially immun.e indh.-idtl.2JS
is a much milder and shorter illness. Hemorrhagic c::-..easles
Management is characterized by a purpuric rash and bleeding from fr.e
All efforts are made to diagnose the serious entities first nose, mouth or bowel
and institute treatment; a specific diagnosis is often not
possible. In this situation, sympto~atic therapy, close
observation, explanation of danger signs to parents an_d
staying away from school until the rash resolves is
recommended. Often drugs and antibiotics are given to a
child with fever and rash. Distinguishing this viral
exanthem from drug-related rash is difficult; intense
itching is common with the latter. Withholding the drug,
sy t t' therapy and observation is recommended.
mp oma 1c · d 'f th
Rechallenge with the medication may be perm1tte , 1 e
rash was mild.
Measles
Meas1es (rub eo1a ) l·s a common and serious
. . childhood
exanthematous illness. Although immunization ~as l~d
to remarkable reduction in mortality, measles is still
estimated to cause 140,000 childhood deaths (2015), of Fig. 11.4: Conjunctiva! congestion and morbOfam rcsl1 of
which 50% occurred in India. measles
11 210 Essential Pediatrics
I
infections. In roseola infantum, the rash appears once fever leads to complications. VZV establishes lifelong lztent
disappears while in measles the fever increases with rash. infection in the sensory ganglia. Reactivation, especi:illy
In rickettsial infections, the face is spared which is always during depressed immunity, leads to the dermatomal rash
involved in measles. In meningococcemia, the upper of herpes zoster.
respiratory symptoms are absent and the rash rapidly
becomes petechial. Drug rashes have history of antecedent Cllnfcal Features
drug intake. Kawasaki disease closely mimics measles; Chickenpox is rarely subclinical; though in some children,
however, glossitis, cervical adenopathy, fissuring of lips, ?nly a few lesions may be present. The peak age of disease
extreme irritability, edema of hands and desquamation is 5-10 years. The prodromal period is short with mild to
are distinguishing clinical features. moderate fever, malaise, headache and anorexia. The rash
appears 24-48 hours after the prodromal symptoms as
Treatment
intensely pruritic erythematous macules first on the trunk.
Treatment is supportive, comprising antipyretics, The rash rapidly spreads to the face and extremities while
maintenance of hygiene, ensuring adequate fluid and it evolves into papules, clear fluid-filled vesicles clouded
caloric intake and humidification. Vitamin A reduces vesicl~s and then crusted :esicles (Fig. 11.5). Sev~ral crops
morbidity and mortality of measles and a single oral dose of .les1~ns ap~ear and simultaneous presence of skin
of 100000 units below 1 year and 200000 units over the les10ns m varymg stages of evolution is a characteristic of
age of 1 year is recommended. Complications should be varicella. The median number of lesions is around 300 but
managed appropriately. may vary from 10 to 1500. Systemic symptoms persist for
Prevention 2-4 days after appearance of the rash. The rash lasts
3-:7 days and leaves behin~ hypopigmented or hyper-
This is a preventable and potentially eradicable disease pigmented macules t~at persist for days to weeks. Scarring
through immunization (Chapter 10). is unusual unless lesions are secondarily infected.
Infections and Infestations I 211 -
Treatment
Management is symptomatic and includes antipyretics
(aspirin is contraindicated due to risk of Reye syndrome
and ibuprofen due to risk of necrotizing fasciitis),
antipruritic agents and good hygiene. The child should
not attend school until no new lesions appear and all
lesions have crusted. Administration of oral acyclovir
(20 mg/kg/ dose four times a day for 5 days) within
24 hours of onset of rash in healthy children reduces the
Fig. 11.5: The polymorphic rash of chickenpox duration of rash by one day and lesions by 25%. There
may be some benefit even if started within 24-48 hours of
Compl/catlons the rash but none beyond 48 hours. IV acyclovir (10 mg/
kg every 8 hours for 14 days) is recommended for patients
Secondary bacterial infections of the skin lesions may with complicated varicella and illness of any severity in
occasionally result in necrotizing fasciitis; usual organisms high-risk patients such as neonates and immuno-
are S. aureus and S. pyogenes. Neurologic complications compromised children.
include meningoencephalitis, acute cerebellar ataxia,
transverse myelitis, LGB syndrome and optic neuritis. Prevention
Other complications include purpura fulminans due to
Prevention against varicella with varicella vaccine and use
antibodies against protein C, CNS vasculitis leading to
of varicella zoster immune globulin (VZIG) for post-
stroke, autoimmune thrombocytopenic purpura, cold
antibody-mediated immune hemolytic anemia and Reye exposure prophylaxis are detailed in Chapter 10. VZIG is
syndrome. fairly expensive and not always available. Other options,
which may be used are intravenous immunoglobulin and
The progressive varicella syndrome is a dreaded oral acyclovir.
complication of chickenpox in the immunocompromised,
neonates, pregnant women and sometimes even healthy Suggested Reading
children, adolescents and adults. This syndrome is
• English R. Varicella. Pediatr Rev 2003;24:372-79.
characterized by continued development of lesions,
• Gershon AA, Breuer J, Cohen JI, et al. Varicell zoster virus
hemorrhagic lesions, coagulopathy and visceral organ infections. Nature Rev Dis Primers 2015; 1: 15016; doi:l0.1038/
involvement including hepatitis, pneumonia and nrdp.2015.16.
encephalitis; mortality rates are high despite therapy. • Wutzler P, Bonanni P, Burgess M, et al. Varicella vaccination-
Chickenpox in pregnancy is associated with increased global experience. Expert Rev Vaccines 2017;16:833-843.
risk of severe disease in the mother. Congenital varicella
syndrome may occur following infection in the first and Infectious Mononucleosis
second trimester at a frequency of 0.4-2% and is Infectious mononucleosis (IM), a syndrome characterized
characterized by skin scarring, malformed extremities, by fever, fatigue, sore throat and lymphadenopathy, is
cataracts and brain abnormalities (e.g. aplasia, most often caused by a herpes virus, Epstein-Barr virus
calcifications). Finally, if the disease occurs in the mother (EBV). Infectious mononucleosis-like illness can also be
5 days before and 2 days after delivery, severe and often caused by toxoplasma, CMV, adenoviruses and primary
fatal neonatal disease may result. HIV infection.
Herpes zoster in children is characterized by a mild
vesicular rash with dermatomal distribution; unlike adults Epidemiology
pain is less and post-herpetic neuralgia unusual. The risk The EBV virus, a DNA virus of the herpes virus family, is
of herpes zoster is more in children who acquire chicken- shed in oral secretions and transmitted by close intimate
pox in infancy, those whose mothers developed varicella contact like kissing or exchange of saliva. The virus
in the third trimester and in the immunocompromised. replicates in the oral epithelial cells then spreads to
salivary glands travels in the B lymphocytes in the blood
Diagnosis
to the lymphoreticular system including lymph nodes,
The diagnosis is clinical and usually not difficult. Chicken- liver and spleen. The CD8 lymphocytes proliferate to check
pox should be differentiated from other vesicular this replication of virus in the B lymphocytes and represent
- 212 Essential Pediatrics
the atypical lymphocytes seen in EBV infection. Like other enlarged adenoids. There is no clear role of acyclovir in
herpes viruses, EBV establishes lifelong latent infection treatment of EBV in the i.mmunocompetent.
after the primary infection with frequent asymptomatic
reactivations. Other Manifestations of EBV Infections
The epidemiology of IM is related to the age of primary EBV has oncogenic potentia~ and. has. been causally
acquisition of EBV infection. In developing countries, most associated with aggressive proliferative disorders such as
EBV infection occurs in infancy and early childhood when virus associated hemophagocytic syndrome, oral hairy
it is either asymptomatic or similar to other childhood leukoplakia and lymphoid interstitial p~eumonitis ~
infections. For this reason, IM is uncommonly seen or patients with AIDS, nasopharyngeal carcm?m?, Burkitt
reported in India. In developed countries, the age of lymphoma, Hodgkin disease. and tumors m i~mu~o
acquisition of EBV infection shifts upwards and thus IM compromised patients (e.g. X-linked lymphoproliferative
is seen more commonly. disease, leiomyosarcoma, CNS lymphoma).
Clinical Features
Suggested Reading
Symptomatic EBV infections in older children and adults
• Dunmire SK, Verghese PS, Balfour HH JR. Epstein-Barr virus
are characterized by insidious onset with symptoms such infection. J Clin Viral 2018;102:84-92.
as malaise, fatigue, fever, headache, nausea, sore throat, • Stanfield BA, Luftig MA, Recent advances in understanding E-B
abdominal pain and myalgia. Examination shows virus. FlOOORes 2017;6:386.
pharyngeal inflammation with exudates and petechiae at
the junction of soft and hard palate, generalized Roseola lnfantum
lymphadenopathy (cervical, less often axillary and Roseola infantum (exanthem subitum, sixth disease) is a
inguinal), mild splenomegaly (50%) and hepatomegaly common childhood exanthematous illness caused most
(10%). Maculopapular rashes are seen in 3-15% and in commonly by a DNA human herpes virus-6 (HHV-6) and
30% of those who have received ampicillin or amoxicillin. less commonly by HHV-7 and echovirus 16. HHV-6 and
Complications are rare and include splenic rupture HHV-7 target the CD4 T cells and like other herpes viruses
following minor trauma, airway obstruction due to can remain latent in the body for several years after acute
enlargement of oropharyngeal lym.P~oid tissu~, infection.
meningitis, seizures, ataxia, myoc~rd1hs, ~emoly~1c The peak age for roseola is between 6 months and
anemia, thrombocytopenia, neutroperua, aplastic aneffila, 3 years. The prodromal period is characterized by upper
interstitial pneumonitis and pancreatitis. respiratory signs such as rhinorrhea, pharyngeal
inflammation, conjunctiva! redness, mild cervical and
Diagnosis occipital adenopathy and sometimes palpebral edema.
Most patients show leukocytosis and absolute lympho- The classic clinical illness is heralded by high fever ranging
cytosis, with presen.ce of atypical ly~phocyte~. The from 38°C to 40°C associated with febrile seizures in
Etlopathogenesls
~fost cases occur between 5 and 15 years of age; infants
are rarely affected due to the presence of transplacentally
acquired maternal antibodies. Man is the only reservoir
of infection; a carrier state does not exist. The incidence is
high in winter and spring; infections occur by direct
contact, airborne droplets and fomites contaminated by
saliYa and urine. The virus proliferates in the respiratory
epithelium and enters the circulation; it then gets localized
to the glandular and neural tissue. The virus has been
isolated from saliva as long as 6 days before and 9 days
after appearance of salivary gland swelling. Secondary
infection rates vary from 40 to 80%. Mumps infection or
immunization is believed to confer lifelong immunity.
Cllnlcal Features
Ag. 11.6: The ·slapped cheek" rash of erythema infectiosum Following an incubation period of 2-4 weeks, the
symptoms begin acutely with fever, malaise and headache.
DNA virus Parvovirus Bl9. This virus has tropism for cells Mumps infection is characterized by unilateral or bilateral
of the erythroid lineage at the pronormoblast stage. parotitis. This presents as earache, jaw tenderness while
The peak age for erythema infectiosum is between chewing, dryness of mouth and swelling at the angle of
5-15 years. Transmission of infection is by the respiratory jaw. The ear lobe may appear to be pushed upwards and
route and the incubation period is 4-28 days (mean outwards. The defervescence and resolution takes about
16-17 days). The prodromal phase is mild and consists of a week. Occasionally other salivary glands including the
low-grade fever, headache and symptoms of mild upper submaxillary and sublingual glands are affected.
respiratory tract infection. The characteristic rash first The occurrence of epididymo-orchitis is common in
appears as erythematous flushing on the face in what is a adolescent boys or postpubertal men (unilateral in 85%
slapped cheek appearance (Fig. 11.6). It spreads rapidly cases) and occurs 1-2 weeks after parotitis. The testes are
to trunk and proximal extremities as a diffuse erythe- enlarged and tender. Some degree of atrophy develops in
matous macular rash that rapidly undergoes central the affected testes; sterility is rare.
clearing to give it a lacy or reticulated pattern. The rash CNS involvement in the form of aseptic meningitis is
gradually fades over a 1-3 weeks period. Complications
include arthropathy, idiopathic thrombocytopenic
purpura and aseptic meningitis. Fifth disease should be
differentiated from measles, roseola, rubella and drug
rash. Treatment is symptomatic.
seen in -1-10% patients with parotitis. Recovery is
generally uneventful. Mumps is one of the commonest
causes of aseptic meningitis in children. The risk of
encephalitis is between 0.02 and 0.3%, with satisfactory
prognosis and of <2%. Other manifestations include
I
Other serious manifestations of parvovirus B19 auditory nerve damage with deafness, cerebellar ataxia,
infection include arthralgia and arthropathy in adolescents facial neuritis, transverse myelitis and Guillain-Barre
and adults, transient aplastic crises in patients with chronic syndrome. Uncommon presentations include pancreatitis
hemolytic anemia, chronic anemia, pancytopenia or (5% may trigger insulin-dependent diabetes mellitus),
marrow suppression, virus associated hemophagocytic mastitis, oophoritis, nephritis and myocarditis.
syndrome in the immunocompromised, hydrops fetalis
in pregnant women and rare episodes of myocarditis in Diagnosis
healthy children and adults. The diagnosis is based on clinical features. Serum amylase
is elevated in almost 90% patients. The diagnosis may be
Suggested Reading
confirmed by serum IgM ELISA. Mumps parotitis needs
• Ramdass P, Mullick S, Farber HF. Viral skin diseases. Prim Care to be differentiated from suppurative parotitis, sub-
2015; 42:517-67
• Servant-Delmas A, Morinet F. Update of the human parVO\'inis B mandibular lymphadenitis, juvenile parotitis, calculus in
19 biology. Transfus Oin Biol 2016;23:5-12 Stensen duct and other infectious causes, e.g. coxsackie A
and cytomegalovirus.
Mumps
Mumps is an acute viral infection characterized by painful Treatment
enlargement of salivary, most commonly the parotid Symptomatic treatment is given in the form of antipyretics
glands. Mumps is caused by an RNA virus of genus and warm saline mouthwashes. Orchitis is treated by bed
Paramyxovirus; only one serotype is known. rest and local support. Aseptic meningitis responds well
• 214 Essential Pediatrics
otognosls
11lc diagnosis is based on history and characteristic clinical
features of iuiymmetric flaccid paralysis. Stool examination
is recommended in every case of acute flaccid paralysis
(AFP). Virus can be detected from onset to 8 or more weeks
11ftcr paralysi!l; the highest probability of detection being
In the first 2 weeks after onset of paralysis. Examination
of cm•brospinal fluid (cell count, Gram stain, protein and
glucose) is useful in eliminating other conditions that
cnuse APP. Current serologic tests cannot differentiate
between wlld and vaccine virus strains. Collection of blood
specimens for culture or serology is not recommended.
Dlfferentlol Diagnosis
It is not possible to clinically differentiate between wild
and vaccine-associated paralytic polio (VAPP). The two Fig. 11.7: Vesicular rash of hand-foot-and-mouth d isease
diseases most commonly confused with polio are Guillain-
Barrc syndrome and transverse myelitis. Other conditions Cllnlcol Features
with a presentation similar to those of paralytic polio-
myelitis include traumatic neuritis, rabies, meningitis/ The onset is with a prodrome characterized by low grade
encephalitis, and illnesses due to toxins (diphtheria, fever, feeling of being unwell, sore throat. This is followed
botulism) (Chapter 19). by development of ulcers/ blisters in the oral cavity mostly
on the posterior aspect, papulovesicular skin rash on the
Treatment palms and soles and less commonly on buttocks, knees,
elbows and genital area (Fig. 11.7). All manifestations may
Treatment should be early and appropriate to the stage not be present in all patients. The illness resolves quickly
and degree of paralysis. Children with bulbospinal polio over the 4-5 days in most patients.
and respiratory paralysis require hospitalization. Children Complications include loss of toe nails or finger nails
with isolated limb paralysis can be managed at home. As 4 weeks after onset of disease which is temporary. Rare
the ncute phase of illness subsides, recovery in muscle complications include aseptic meningitis, encephalitis,
power is helped by physiotherapy, ambulation and polio-like paralysis, myocarditis and respiratory distress
prevention of deformities. Some children require orthosis syndrome. Mortality is reported in HFMD outbreaks
at some stage for ambulation. Others with fixed particularly due to enterovirus 71 with neurologic
deformities and con tractures require orthopedic complications, from China, Vietnam, Taiwan and
intervention. Malaysia. Some experts believe that HFMD enteroviruses
are occupying the ecologic niche created by eradication
Prevention of polioviruses.
The availnble vaccines and the recommended schedule
are discussed in Chapter 10. Diagnosis
Suggested Reading Diagnosis is clinical and the disease should be differen-
tiated from other illnesses causing oral ulcers such as
• Pollo Global Eradication Initiative. www.polioeradication.org
• World Health Organization. Poliomyelitis. www.who.int
herpangina1 herpetic gingivostomatitis and aphthous
ulcers and also from chicken pox and insect bite allergy.
Hand-Foot~and-Mouth Disease (HFMD)
Treatment and Prevention
HFMD is a common viral illness affecting primarily
children below the age of 5 years. The illness is caused by Treatment is symptomatic with analgesics and soft diet.
viruses of the enterovirus genus, belonging to family Isolation of affected children at home and promotion of
Picornaviridae. This genus includes other infection hand hygiene is important. There is no vaccine available
causing viruses, including poliovirus, ECHO virus, against HFMD.
Coxsackie virus and enteroviruses. Though many viruses
can cause HFMD, Coxsackie virus A16 and enterovirus Suggested Reading
71 are the most common. The disease commonly presents • Hand-foot-and-mouth disease. www.mayoclinic.org
as outbreaks often in preschools and transmission is • Koh WM, Badaruddin H, La H, et al. Severity and burden of
by direct contact with an affected patient or infected hand-foot-and-mouth disease in Asia. BMJ Glob Health 2018; 3(1):
fomites. e000442
----
- 216
. f fulminant hepatitis, which is more common as
V1lol Hepatltts signsdo ces and lends to death in 70-90% of the patients
age a van ' · 1 ·
H~r<1titis is a gent."ral term ml'aning inflammation of the . ts ,,,1, survive' neither funchona nor patholoi>ic:
lh~ nnd c,,n ~ c.u1sed by a Yariety of different hepato-
In pa t1en · 0 . o·
common despite the widespread necrosis
u:
tropic YintSC$ such as hep~titis A, C, D and E. Hepatitis seque1ae 'are .
Infection with HA V does not le~d to chrome or p~rSIStent
. ·
A and E a.r e responsible for most of the waterborne
(community acquirt'Cl) hepatitis, while 13, C and D are h epa ti.ti.s. In some patients, there is a prolonged febrile
. cho\e-
static phase and some patients have a re1apsmg pattern.
responsible for post-transfusion hepatitis. Since a
ronsidernble number of cases of both post-transfusion and Diagnosis
rommun\ty-..'1cquired hepatitis are not identified as being
Laboratory evaluation of li~e.r f~nction in~ludes
cau~~i by hepatitis A-E, investigators have sought to
estimation of total and direct b1hrubm, transammases,
identifr other potentially hepatotropic viral agents,
alkaline phosphatase, prothrombin time, total protein and
including hepatitis G vims, TT virus and SEN virus.
albumin. The specific diagnosis of acute hepatitis A is
made by finding anti-HAV IgM in the serum. Anti-HAV
Hepatitis A
JgM is detectable about 3 weeks. aft~r exposure, always
Hepatitis A is caused by infection with the hepatitis A by the time symptoms occur, its hter mcreases over
\ints (HAV), ,1 nonenveloped RNA virus. In humans, a 4 to 6 weeks, then decline to non-detectable levels within
single serotype of HAY exists. HAY infection induces 6 months of infection. As IgG anti-HAV persists lifelong
lifelong protection against reinfection. HAV is extremely after acute infection, detection of IgG anti-HAV alone
resistant to degradation by environmental conditions, a indicates past infection.
property th.1t allows its maintenance and spread within Hepatitis A needs to be differentiated from other viral
populations. It is spread ,·ia the fecal oral route through hepatitis chiefly E, and sometimes also from Wilson
contaminc1ted food and water, and person-to-person disease and autoimmune hepatitis.
spread tmder poor sanitary conditions. The severity of the
disease increases with age at time of infection. In children Treatment
below age 5, infection is asymptomatic or presents as an
acute tmdifferentiated febrile illness. Classic hepatitis is Therapy is supportive and is aimed at maintaining
seen in older children, adolescents and adults. Hence in adequate nutrition. There is no evidence to suggest that
developing countries with poor environmental hygienic restriction of fats has any beneficial effect on the course of
conditions where most are infected in childhood, the disease. Eggs, milk and butter actually help provide a
symptomatic disease is less common and outbreaks rare. correct caloric intake. Antiviral agents have no role
India is a country with intermediate endemicity, a subset because the hepatic injury appears to be immuno-
of population which is of good socioeconomic status pathologically mediated. Referral to a liver transpiant
escapes natural infection in childhood and gets centre is appropriate for patients with fulminant hepatitis.
symptomatic disease as adults. Steroids are sometimes indicated in patients with
cholestatic/relapsing hepatitis.
Cllnlcol Features
Prevention
The incubation period ranges from 10 to 50 days (median
30 days), during which the patient remains asymptomatic The ideal preventive strategy is improvemen t in
despite active replication of the vims. Thereafter, there is sanitation, hygiene and water supply. Immunization is
a short prodromal phase lasting for up to a week very effective (Chapter 10). Irnmunoglobulin G may be
characterized by symptoms like loss of appetite, fatigue, used for postexposure prophylaxis. If administered within
abdominal pain, nausea and vomiting, fever, diarrhea, 2 .weeks of exposure, it either prevents development of
dark urine and pale stools. In older patients, this disease or reduces its severity.
pro~r~mal ~hase is follmved by an icteric phase, during
which Jaundice de:elops at total bilirubin levels exceeding Suggested Reading
2-4 mg/dL and liver enzymes in hundreds/thousands. • Ma~~r P, Arora NK. Epidemiological transition of hepatitis A in
~e. icteric phase generally begins within 10 days of the India: issues for vaccination in developing countries. Indian JMed
Res 2008; 128:699-704.
rm~al SY_mptom~. Fever improves after the first few days
• Satsangi S, Chawla YK. Viral hepatitis: Indian scenario. Med J
of J~und1c~. During the next few weeks in the convalescent Armed Forces India 2016; 72:204-10.
period, patient shows complete recovery.
In. around 0.1 to 1% of patients, extensive necrosis of Hepatitis B
th~ liver oc.curs during the first 6-8 weeks of illness. In
!his c~se, high fever, marked abdominal pain vomiting Hepatitis B viru~ is a 3.2 Kb, circular, partially double
1aund1ce
. and the d evelopment of hepatic encephalopathy
' ' stranded DNA virus containing 3200 nucleotides coding
assooated with coma and seizures occur. These are the for core protein (HBcAg), precore protein (HBeAg),
envelope glycoprotein (HBsAg), a DNA polymerase with
Infections and Infestations I 211 -
•
symptoms. This is called the immunotolerant phase. In the weekly injections for 6 months. Studies indicate that
second and third decade of life, the phase of immune almost 30% lose HBeAg and halt liver damage with
tolerance converts to a phase of immune clearance wherein treatment and 90% of these continue to be HBsAg negative
there is immune-mediated destruction of the virus infected over 4-8 years follow-up. Antiviral resistance does not
cells leading to abrupt increase in liver enzymes and less occur. The main limitations are treatment related side
commonly symptoms of hepatitis and rarely hepatic effects such as flu-like symptoms, headache, depression,
decompensation. In some this immune clearance is loss of appetite, anemia, leukopenia and thrombo-
associated with loss of HBeAg and development of anti- cytopenia. Promising results are emerging using
HBe antibody and later clearance of HBsAg (0.6% of pegylated IFN in adults with chronic hepatitis B, but data
infected children per year) (Fig. 11.8). In most cases, this in children are lacking.
phase is associated with only temporary loss of HBeAg Oral lamivudine is more convenient to take with fewer
and clearance of HBV DNA with return of antigenemia. side effects and is usually prescribed for I year to begin
Several such episodes may occur over the years with with. There is reduction in liver damage with loss of
development of chronic hepatitis and later cirrhosis and HBeAg but limitations are relapse of viremia and
hepatocellular carcinoma (HCC). In children infected in antigenemia on stopping therapy and high incidence of
early childhood, the initial phase is of active replication, development ofYMDD mutants (10-30% after 1 year and
followed by non-replication and remission of disease or 60-70% after 5 years).
progression to chronic liver disease and HCC. Combinations of either INF-ex 2a or INF-ex 2b with
Treatment
lamivudine have comparable effects and slightly better
results than monotherapy in children affected by chronic
The short-term goals of therapy are to enhance the activity hepatitis. Other drugs recently approved for HBV infection
of the immune system to fight the virus, prevent viral in children include adefovir (above 12 years), entecavir
11 21a Essential Pediatrics
(above 16 years), telbivudine (above 16 years) and more coinfection with HIV) and receipt of blood transfusions
recently tenofovir (above 12 years) (see Chapter 12). prior to the period when HCV testin~ became routine.
HCV is not transmitted by breastfeedmg. Transmission
lmmunoprophylaxls by unsafe injections, drug abuse, tattooing are other routes
Hepatitis B immunoglobulin (HBIG) is used in the post- for disease transmission. Unlike HBV, HCV is not
exposure prophylaxis of newborns of HBV-infected transmitted to household contacts and sexual transmission
women. It is administered intramuscularly as soon as is infrequent.
possible after birth and should be given concurrently with
HBV vaccine, at a different site. The dose for infants is 0.5 C//n/ca/ Features
mL. Combination of HBIG and HBV vaccination in infants In adults, 85% of patients exposed to HCV will develop
born to HBsAg positive mothers prevents transmission chronic infection, of which approximately 10-20%
in approximately 95% of those at risk (see Chapter 10). develops cirrhosis and some hepatocellular carcinoma.
Chronic HCV is a common indication for liver transplant
Suggested Reading in the developed nations. However, the prognosis of
• Nelson NP, Easterbrook PJ, McMahan BJ. Epidemiology of hepatitis childhood HCV infection is generally good. A significant
B virus infections and impact of vaccination on disease. Clin Liver percentage (-40%) of vertically infected children
Dis 2016; 20:607-28. spontaneously clears HCV over a few years. The rate of
spontaneous clearance reduces as age of acquisition of
Hepatitis D
infection advances. Even chronically infected children
Hepatitis delta virus (HDV) was first detected as a new remain asymptomatic; most have normal liver enzymes
nuclear antigen in the hepatocytes of patients infected with and a few changes on liver biopsy. Progression to chronic
hepatitis B virus (HBV) and was frequently associated with disease, hepatic failure and carcinoma are rare in children.
severe acute or chronic hepatitis. Transmission of HDV
requires either co-infection with HBV or superinfection Diagnosis
in individuals who are HBV carriers. Although HDV The diagnosis of HCV infection is based on detection of
infection is closely associated with HBV, HDV clearly antibodies against recombinant HCV antigens by enzyme
belongs to a distinct virus group. Currently, HDV is immunoassay or rapid immunoblot assays or by detection
assigned a floating genus, Deltavirus. of HCV RNA using nucleic acid tests. Enzyme irnmuno-
assays are fairly sensitive but less specific especially wi th
Hepatitis C
false positive results in patients with elevated globulin
Hepatitis C virus (HCV) was recognized in 1989 as a major levels such as those with autoimmune hepatitis. Recom-
cause of non-A, non-B hepatitis. HCV is an enveloped, binant irnmunoblot/ immunochromatographic assays are
single-stranded, positive-sense ribonucleic acid (RNA) less sensitive but more specific than enzyme immunoassc.y
virus, classified as an independent genus (Hepacivirus) in detecting anti-HCV antibodies. Hence the EIAs are
Viral Variants
The HCV RNA-dependent RNA polymerase lacks proof-
reading ability, which results in HCV being genetically
recommended as screening tests and the recombinant
imrnunoblot assay as confirmatory tests. Patients with
positive EIA and negative immunoblot assays are labeled
as indeterminate and repeating tests after 4-6 weeks in
such a setting is recommended. Antibodies against HCV
heterogeneous. Based on analysis of HCV sequences, six are non protective and may last for life even if the patient
major HCV genotypes are recognized. HCV genotypes has cleared HCV from the body. Diagnosis of perinatal
1 and 2 are the most prevalent worldwide. HCV infection, early infection (in the first 4-8 weeks) or active
genotype 3 is most common in Australia and the Indian infection is by performing the HCV RNA PCR.
subcontinent. The viral genotypic distribution in children
generally parallel that reported regionally in adults. HCV Therapy
genotype 1 correlates with higher serum viral levels and Most childhood HCV infections do not need specific
a less favorable response to antiviral treatment. therapy. Treatment is indicated only in children with
persistently elevated liver enzymes and abnormalities on
Epidemiology liver biopsy. Standard treatment in these children includes
The worldwide prevalence of HCV infection is approxi- interferon 2a (preferably pegylated) with or without
mately 3%, which represents an estimated 170 million ribavirin for 24-48 weeks depending on the genotype. A
infected persons. Infection occurs due to contact with number of new anti-viral medications (sofosbuvir,
blood and body fluids of infected people. The primary velpatasvir, ledipasvir, simprevir) have been approved for
modes of infection in children are vertical transmission use in patients with hepatitis C, including those with
from infected mothers (rates ranging from 2 to 10% compensated cirrhosis, HIV co-infection or severe kidney
depending on the level of maternal viremia and disease (see Chapter 12).
Infections and Infestations 219 -
same time as fever. Aedes mosquitoes may acquire the en in older children, adolescents and adults:....
usua lly Se . . . . ......,d
virus when feeding on an individual. can be described under three phases. Febnle, cnttcal <lnd
recovery.
Pothophyslology
Febrile plrase: Characterized by sudden onset ~f high.
The major pathophysiology that differentiates severe grade fever that may last for 2-7 days, t~ere 1s facial
dengue from dengue fever is plasma leakage and flushing, skin erythema, bodyache, n:i~algia, arthralgia,
abnormal hemostasis leading to rising hematocrit values, headache, anorexia, nausea and v.or:ruting. Occasionally
moderate to marked thrombocytopenia and varying the child may have sore throat, miected pharynx and
degrees of bleeding. The cause of abnormal leakage of conjunctiva! injection. ~ posi~ive tourniq~et test and
plasma is not entirely understood. However, rapid minor hemorrhagic manifestations (petech1ae, mucosa!
recovery without residual abnormality in vessels suggests bleeding from nose and gums) may be seen in some
it to be the result of release and interaction of biological patients. Liver may be enlarged and tender from 2 toSdays
mediators, capable of producing severe illness with and indicates risk for developing severe illness. There is
minimal structural injury. progressive decrease in total white cell count and platelet
The pathogenesis of dengue and severe dengue count.
infection is not clear. It is observed that sequential infection
with any two of the four serotypes of dengue virus results Critical phase: During defervescence, 3-7 days from onset
in DHF /DSS in an endemic area. It is suggested that of fever, the patient may show bleeding and shock \\i th
antibodies produced during the first infection are able to fall in platelet count and increase in packed cell volume
neutralize a second viral infection w ith the same serotype. (PCV). Some children show organ dysfunction with severe
However, when no neutralizing antibodies are present (i.e. hepatitis, encephalitis or myocarditis and/or severe
infection due to another serotype), the second infection is bleeding, even in the absence of plasma leakage or shock.
under the influence of enhancing antibodies and the
RecovenJ phase: After 24-48 hours in critical phase, a
resulting infection and disease are severe. It is proposed
gradual reabsorption of extravascular compartment fluid
that serotype cross-reactive antibodies generated from
takes place in next 48-72 hours. The general well-being
previous infection with a particular dengue virus serotype
improves, appetite returns, gastrointestinal symptoms
are not specific for other serotypes. Hence, they bind to
abate, hemodynarnic status stabilizes and diuresis ensues.
the virions but do not neutralize them, and instead
Some patients may have a rash of 'isles of white in the sea
increase their uptake by antigen presenting cells (tissue
dendritic cells, monocytes, macrophages). Enhanced of red.' Others e xhibit pruritus, bradycard i2 and
electrocardiographic changes; respiratory distress due to
antigen presentation by these cells results in activation
and proliferation of memory T cells, and release of pulmonary edema is uncommon. PCV stabilizes er may
be lower due to dilution. While leukocyte counts rise after
cytokines that contribute to the pathogenesis of DHF /DSS.
defervescence, recovery of thrombocytopenia may take
Endothelial cell dysfunction manifests as increased longer.
capillary permeability with microvascular leak,
hemoconcentration and circulatory insufficiency. The Unttsttal features: A few patients may present with
transient nature of plasma leakage suggests that this might persistent thrombocy topenia mimicking idi opa th~c
be mediated by a soluble mediator. Dengue viral infection thrombocytopenia, hemophagocy tic lymphohistioc~·tos1s
is commonly associated with thrombocytopenia, due to and an extended course of illness in form of multi-organ
molecular mimicry between dengue virus proteins dysfunction (extended dengue syndrome). Dengue in
(especially NSl) and endogenous self-proteins. There is immunocompromised children shows higher incidence
activation of blood clotting and fibrinolytic pathways. of organ dysfunction and longer time for platelet
Mild disseminated intravascular coagulation, liver injury recovery.
and thrombocytopenia contribute to hemorrhage. Liver
may show diffuse hepatitis with focal necrosis and Different/of Diagnosis
steatosis; viral antigen may be detected on immuno-
Differential diagnosis includes other hemorrhagic fever,
histochemistry. Central nervous system involvement is
chikungunya infection, influenza, malaria, enteric. feve~
attributed to direct neurotropic effect of the virus.
leptospirosis and less commonly meningococcemta and
rickettsiosis. Malaria, leptospirosis, flu, enteric fever an
Clfnlca/ Manifestations chikungunya infections may be coinfected with dengue·
Dengue infection has varying clinical presentations and The features of chikungunya infection are similar t~
often with unpredictable clinical evolution and outcome. dengue. However, fever is of shorter duration,.ants
Incubation period varies between 3 and 7 days. Infants thrombocytopenia and bleeding are less frequent. Patietl 1
and young children may present with an undifferentiated with chikungunya often have skin eruptions, mucosa
febrile illness. The classic presentation of dengue fever is lesions, polyarthralgia and encephalopathy.
Infections and Infestations 1221 -
Following clinical and laboratory features suggest Antibody determination needs careful interpretation.
presence of severe dengue infection: Following primary dengue infection, 80% patients show
clinical criteria: Acute onset high-grade fever, detectable IgM antibodies by day 5, 99% by day 10 that
hemorrhagic manifestations (positive tourniquet test), peak by day 14 and are undetectable by 2-3 months. IgG
tender hepatomegaly, effusion in body cavities and/ antibodies rise later, peak to levels lower than IgM, decline
shock. slowly and remain detectable at low levels for life.
Diagnosis of primary dengue infection is thus based on
Laboraton1 criteria: Thrombocytopenia (~100 000 cells per
nun3; <1-:-2 platelets per oil immersion field), rising elevated IgM antibodies.
hematocnt
Management
Toimiiquet test: This test is p a rt of the WHO case Undifferentiated fever: Patients have non-specific symp-
defi_n_ition for d.engue, and a marker of capillary toms. Treatment consists of paracetamol for fever and
fragility. The ~est is ?one by inflating the blood pressure regular monitoring for development of any complications.
c~ff to_a pomt midway between the systolic and
diastolic blood pressure for 5 minutes. The cuff is Dengue infection without warning signs: Patients with
deflated and removed. After w aiting for 2 minutes, the fever, bodyache, rashes or minor bleeding may be treated
number of petechiae is counted in the antecubital fossa. symptomatically. Fever and bodyache are best treated
!he. presence o~ :o or. m~re petechiae per 1 square inch
indicates a positive finding. This finding is present in
with paracetamol. Salicylates and other non-steroidal, anti-
inflammatory drugs should be avoided as these may
more than 50% of cases. predispose to mucosa! bleeds. Child should be encouraged
to drink plenty of fluids. In epidemic situations, the
Laboratory Investigations primary care physician or health w orker should monitor
for warning signs (see below) along with hematocrit (PCV)
Children with severe dengue infection show increasing and platelet count, if possible.
PCV and low platelet and leukocyte counts with
lymphocyte predominance. A low leukocyte count in a Dengue with warning signs: Children w ith suspected
child with febrile illness during the endemic season dengue infection w ho have any of the following need
suggests possible dengue infection. While malaria and hospitalization: (i) abdominal pain or tenderness,
enteric fever may have low white cell counts, leukopenia (ii) persistent vomiting, (iii) clinical fluid accumulation,
is more severe in dengue. (iv) mucosa} bleeding, (v) lethargy, restlessness, (vi) liver
Blood levels of total protein and albumin are reduced, enlarged >2 cm, (vi) increase in PCV with concurrent or
more marked in patients with shock. Levels of rapid decrease in platelet count.
transaminases are raised; higher increase in SGOT than These patients should be admitted in hospital and need
SGPT suggests dengue rather than other virus infection. intravenous fluids. Crystalloids are the preferred fluids.
Patients with severe dengue may show hyponatremia and In the hospital, all children without hypotension should •
acidosis, with increase in urea and creatinine. X-ray chest be given Ringer lactate or normal saline infusion at a rate
or ultrasound examination may show varying degrees of of 7 mL/kg over one hour. After one hour, if PCV has
pleural effusion that is more common on the right, but decreased and vital parameters are improving; fluid
occasionally bilateral. Ultrasound examination of infusion rate should be decreased to 5 mL/ kg over next
abdomen may show ascites and enlarged gallbladder. hour and to 3 mL/ kg/ hour for 24-48 hours w ith frequent
monitoring of PCV and vital param eters. When the pa tient
Confirmatio11 of diag11osis of dengue is established by the is stable as indicated by normal blood pressure, good oral
following: intake and urine output, the child can be discharged
Direct methods: Virus isolation by culture; genome (Fig. 11.9).
detection by PCR; NSl antigen detection. If at 1 hour, the PCV is rising and vital parameters do
Indirect methods: IgM detection; IgG detection. not show improvement, the infusion rate is increased to
10 mL/kg over next hour. In case of no improvement, fluid
Virus isolation or PCR requires the sample to be infusion rate may further be increased to 15 mL/kg in the
obtained within the first 5 days of fever, is technically 3rd hour. If no improvement is observed in vital parameters
demanding, not universally available and hence of limited and PCV at end of 3 hours, colloids are given at 10 mL/ kg.
practical use. NSl antigen is a highly conserved Once PCV and vital parameters are stable, the infusion rate
glycoprotein of dengue virus and secreted during the is gradually reduced and stopped over 24-48 hours.
initial phase of illness. It disappears as antibodies appear
and hence declines as illness advances and in secondary Severe dengue: Children having any of the following:
dengue infections. The specificity is -100% and sensitivity (i) Severe plasma leakage leading to shock or fluid
in the first 4 days of illness is 90% in primary dengue and accumulation with respiratory distress; (ii) Sever e
70% in secondary dengue infection. bleeding; (iii) Severe organ involvement: high AST, ALT
- 222 Essential Pediatrics
Hospltall~
No Improvement Improvement J
r - ~sr~ __
Normal saline or
1
[_ DSSIV
~ _L_ J
until stable for 24 Infusion with monitoring
as In Fig. 11 .9 r--;-
Collolds transfusion I
Assessment at 3 hours
10 mUkg 1__e1ood
- - - . - - -- -1
Discharge when
"[A~essmen~
stable for 24-48 hr
No improvement
- ,
Colloids 10 mL/kglhr I
~---*----
Improved
~-t
[ No Improvement l
No improvement - ~
I Look for anemia, acldosls-.-m-y-ca-r-dlal; treat accordinglyJ
Look for anemia, acidosis
and myocardial dysfunction;
treat accordingly Fig. 11.1 O: Management of severe dengue fever
Prognosis Epidemiology
Dengue fever is a self-limited disease but mortality in The rural cycle of chikungunya transmission involves
severe dengue may be as high as 20-30%, if untreated. Aedes africa11s, A. Ja11cifer, and wild primates, while the
Early recognition of illness, careful monitoring and urban cycle involves A . ae~Jpfi and humans. In rural cycle
appropriate fluid therapy has resulted in considerable (seen in Africa), the disease is endemic with a small
reduction of case fatality rate to <1 %. Early recognition of number of cases occurring in most years. In urban areas,
shock is of paramount importance as the outcome of a the outbreaks are sporadic and explosive with infection •
patient with DSS d epends on the duration of shock. If of a large population within weeks. In Asia, the virus may
shock is identified when pulse pressure starts getting be maintained in urban cycle, with A. ae~;p ti or require
narrow and IV fluids are administered at this stage, the reinoculation before onset of epidemic. Outbreaks occur
outcome is excellent. during the rainy season, associated with the population
density of the mosquito vector, which breeds in household
Prevention containers and puddles with peak activity in mid-morning
Preventive measures are directed towards elimination of and late afternoon . After an epidemic, the disease wanes
adult mosquitoes and their larvae. During epidemics, for years b ecau se a large proportion of the population is
aerial spraying/ fogging with malathion is recommended immune.
for adult mosquitoes. Larval control m easures by source
reduction and use of larvicides are even more crucial. Clinical Features
Mesocyclops, the shell fish are credited to eat and The disease h as sudden onset, with incubation period of
effectively eliminate larvae of Aedes. The strategy has been 2-12 days. Infection is characterized by fever, headache,
used with success by Australian scientists working in fatigue, n ausea, vomiting, rash and muscle and joint pain.
Vietnam by growing shell fish in ponds and water traps. Fever rises abruptly to 103- 104°F and is accompanied by
A. aegypti breed in and around human dwellings and rigors that last for 2-3 days. Joint pain appears suddenly
flourish in fresh water. Special drives must be launched and is severe in intensity; the arthralgia and arthritis is
during and soon after the rainy season to interrupt their polyarticular, migratory, and chiefly affects small joints
breeding. There should be no stagnation of water in the of hands, wrist, ankle and feet with less involvement of
bathroom, kitchen, terrace, lawn and other open places; larger joints. The joint pains may continue for months after
stored water should be covered. Cooperation from every the illness. Headache is present in 80% of cases in the acute
house owner, public establishment and the government stage. Photophobia and retro-orbital pain m a y also occur.
- 224 Essentlal Pediatrics
D
2010: A cross sectional observational study. J Med Virol 2016; 88:
provirus. The provirus can remain dormant for extended
923-30.
• Guaraldo L, Wakimoto MD, Ferreira H, et al. Treatment of periods. HIV-1 transcription is followed by translation. A
chikungunya musculoskeletal disorders: a systematic review. capsid polyprotein is cleaved to produce, among other
Expert Rev Anti Infect Ther. 2018 Mar 13. doi:l0.1080/ products, the virus-specific protease (p 10). This enzyme
14787210.2018.1450629. is critical for HIV-1 assembly. The RNA genome is then
incorporated into the newly formed viral capsid. As the
HIV INFECTION, ACQUIRED
new virus is formed, it buds through the cell membrane
IMMUNODEFICIENCY SYNDROME
and is released.
HIV infection has become an important contributor to HIV-2 is a rare cause of infection in children, more
childhood morbidity and mortality, especially in prevalent in western and southern Africa. If HIV-2 is
developing countries and has undone many of the major suspected, a specific test that detects antibody to HIV-2
gains in child health. peptides should be used.
Epidemiology Transmission
It is estimated that more than 36 million persons Transmission of HIV-1 occurs via sexual contact,
worldwide were living with HIV infection at the end of parenteral exposure to blood, or vertical transmission frorn
2016; 2.lmillion of these were children under 15 years of mother to child. The primary route of infection in the
age. More than 90% of HIV-infected individuals live in pediatric population is vertical transmission. Most large
developing nations. Sub-Saharan Africa accounts for studies in the United States and Europe have documented
nearly 90% of the world population of HIV-infected mother-to-child transmission rates in untreated women
children. India and Thailand dominate the epidemic in between 12 and 30%. In contrast, transmission rates in
Southeast Asia, with expansion into Vietnam, China, and Africa and Asia are higher, up to 50%.
Infections and Infestations j 225 -
Vertk"l tr"nsmission of HIV cnn occur during the normally have a relative lymphocytosis. Therefore, for
it\tr.:\\\tNinc ()\' intrapmtum periods, or through breast- example, a value of 1500 CD4 cells/mm3 in children
ft~-..Hn~- Up t\) ~0% of infected newborns nre infected in <1 year of age is indicative of severe CD4 depletion and
id<f\. Ttw hif-ht'st pcrccntnges of HIV-infected children is comparable to <200 CD4 cells/mm 3 in adults.
acquire the \'irus intrnpnrtum. Brenstfeeding is an Lymphopenia is relatively rare in perinatally infected
iinpl rtnnt r\)\\tc of transmission, especially in the children and is usually only seen in older children or those
dc\'t'loping countries. The risk factors for vertical with end-stage disease.
tr'-lnsmission include pre term delivery (<34 weeks B cell activation occurs in most children, as evidenced
sc::t.1tion), a low m«tcrnal antenatal CD4 count, use of by hypergammaglobulinemia with high levels of anti-
illicit dru~s during pregnancy, >4 hours duration of HIV-1 antibody. This response may reflect both
n1ptu~'Ci ml'mbrnnes and birth weight <2500 g. dysregulation of T cell suppression of B-cell antibody
Transfusions of infected blood or blood products have synthesis and active CD4 enhancement of B lymphocyte
aC'i..'O\tntt.•d for n proportion of pediatric AIDS cases. Heat humoral responses.
t.reatm~·nt of fo.ctor Vlll concentrate and HIV antibody CD4 depletion and inadequate antibody responses lead
screenmg of donors have virtunlly eliminated HIV to increased susceptibility to various infections and clinical
trons.mission to children with hemophilia. Blood donor features vary with the severity of immunodeficiency.
screening hns dramatically reduced, but not eliminated,
the risk of transfusion-associnted HIV infection. Sexual Clinical Features
contact is a mnjor route of transmission in adolescents. The clinical manifestations of HIV infection vary widely
among infants, children and adolescents. In most infants,
Natural History physical examination at birth is normal. Initial signs and
Before highly active antiretroviral therapy (HAART) was symptoms may be subtle and non-specific, such as
a\'ailable, three distinct patterns of disease were described lymphadenopathy, hepatosplenomegaly, failure to thrive,
in children. Approximately 10-20% of HIV-infected chronic or recurrent diarrhea, interstitial pneumonia or
newborns in developed countries presented with a rapid oral thrush and may be distinguishable from other causes
disease course, with onset of AIDS and symptoms during only by their persistence. While systemic and pulmonary
the first few months of life; if untreated, these patients findings are common in the United States and Europe,
died from complications by 4 years of age. In resource- chronic diarrhea, wasting, and severe malnutrition
poor countries, >85% of the HIV-infected newborns may predominate in Africa. Symptoms more common in
have such a rapidly progressing disease. children than adults include recurrent bacterial infections,
chronic parotid swelling, lymphocytic interstitial
It has been suggested that if intrauterine infection
pneumonitis (LIP), and early onset of progressive
coincides with the period of rapid expansion of CD4 cells
neurologic deterioration.
in the fetus, it could effectively infect the majority of the
Pediatric HIV disease is staged using two parameters:
body's immunocompetent cells. Most children in this
Clinical status (Table 11.3) and degree of immunologic
group have a positive HIV-1 culture and/or detectable
impairment (Table 11.4).
virus in the plasma in the first 48 hours of life. This early
evidence of viral presence suggests that the newborn was
Opportunistic Infections
infected in utero. In contrast to the viral load in adults,
the viral load in infants stays high for at least the first Children with HIV infection and advanced or severe
2 years of life. immunosuppression are susceptible to develop various
Majority of perinatally infected newborns (60-80%) opportunistic infections. The important pathogens
present ·w ith the second pattern: Slower progression of include: Pneumocystis jirovecii, Cryptosporidium, Crypto-
disease with a median survival of 6 years. Many patients coccus, lsospora and CMV.
in this group have a negative viral culture or PCR in the
first week of life and are, therefore, considered to be Respiratory Diseases Compllcotlng HN Infection
infected intrapartum. In a typical patient, the viral load P. jirovecii (previously P. carinii) pneumonia is the
rapidly increases by 2-3 months of age, and then slowly opportunistic infection that led to the initial description
over 24 months. The third pattern (i.e. long-term survivors) of AIDS. This is one of the commonest AIDS defining
occurs in a small percentage (<5%} of perinatally infected illnesses in children in the US and Europe; most cases
children who have minimal or no progression of disease occur between 3rd and 6th months of life. Even if a child
With relatively normal CD4 counts and very low viral develops the illness while on prophylaxis, therapy may
loads for longer than 8 years. be started with cotrimoxazole. With the use of appropriate
HIV-infected children have changes in the immune therapy, the mortality decreases to less than 10%. Risk
system that are similar to those in mv-infected adults. factors for mortality are severity of the episode and
CD4 cell depletion may be less dramatic because infants severity of the immunosuppression.
--
- 226
Table 11.3: WHO clinical staging.of HIV/ AIDS.for children wit~ confirmed HIV Infection
Cllnlcal stage 1
Asymptomatic
Persistent generalized lymphadenopathy
Clinical stage 2
Unexplained~ persistent hepatosplenomegaly
Papular pruritic eruptions
Fungal nail infection
Angular cheilitis
Lineal gingival erythema
Extensive wart virus infection
Extensive molluscum contagiosum
Recurrent oral ulceration
Unex:plaineda persistent parotid enlargement
Herpes zoster
Recurrent or chronic upper respiratory tract infections (otitis media, otorrhea, sinusitis, tonsillitis)
Clinical stage 3
Unexplaineda moderate malnutrition or wasting not adequately responding to standard therapy
Unexplaineda persistent diarrhea (14 days or more)
Unexplained• persistent fever (above 37.5°C intermittent or constant, for longer than one month)
Persistent oral candidiasis (after the first 6-8 weeks of life)
Oral hairy leukoplakia
Acute necrotizing ulcerative gingivitis/periodontitis
Lymph node TB
Pulmonary TB
Severe recurrent bacterial pneumonia
Symptomatic lymphoid interstitial pneumonitis
Chronic HIV-associated lung disease including bronchiectasis
Unexplained anemia (<8 g/dl), neutropenia (<0.5 x 109/L) or chronic thrombocytopenia (<50 x 109/L)
Clinical stage 4b
Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy
Pneumocystis pneumonia
Recurrent severe bacterial infections (empyema, pyomyositis, bone, joint infection, meningitis; excluding pneumonia)
Chronic herpes simplex infection (orolabial or cutaneous for >1 month duration; visceral at any site)
Esophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
Extrapulmonary/disseminated TB
Kaposi sarcoma
Cytomegalovirus infection (retinitis or CMV infection affecting another organ, with onset at age > 1 month)
Central nervous system toxoplasmosis (after one month of life)
Extrapulmonary cryptococcosis (including meningitis)
HIV encephalopathy
Disseminated endemic mycosls (extrapulmonary histoplasmosls, coccidloldomycosls)
. Disseminated non-tuberculous mycobacterial Infection
Chronic cryptosporidiosls (with diarrhea)
Chronic isosporlasls
Cerebral or B cell non-Hodgkin lymphoma
. Progressive multlfocal leukoencephalopathy
Symptomatic HIV (associated nephropathy or cardlomyopathy)
•unexplained refers to where the condition Is not explained by other causes
bAdditional specific conditions may be included In the regional classlflcalions (e.g. reactivation of American trypanosomiasis menlngoencephalitis
and/or myocarditls In Americas region, penlcllllosls In Asia and HIV-associated rectovaglnal fistula In Africa) '
Infections and Infestations
I 221 •
r.
I
Table 11.4: -Clas~iflcatlo~ oflmmu~; ~~ppres;lo;i~ ~hildren (CD4 levelsinralaij;;n t~ sa""verity of Immune suppre;slo~)
• • - • : •
' .
HIV-associated Age-related CD4 cell values
immunodeficiency < 11 months 12-35 months 36-59 months ~5 years
Not significant >35% >30% >25% >500 cells/mm3
(normal CD4 cells)
Mild 30-35% 25-30% 20-25% 350-499 cells/mm 3
Advanced 25-30% 20-25% 15-20% 200-349 cells/mm3
severe <25% <20% <15% <15%
<1500 cells/mm3 <750 cells/mm3 <350 cells/mm 3 200 cells/mm3
Rec11rre11t bacterial pneumonia may be present in up to 90% Fungal infections present as a part of disseminated disease
HIV-infected children. Initial episodes often occur before in immunocompromised children. Primary pulmonary
the development of significant immunosuppression. As fungal infections are uncommon.
the immunosuppression increases the frequency increases.
Lymphoid interstitial pneumonitis (LIP) has been recognized
The common pathogens for community-acquired
as a distinctive marker for pediatric HIV infection and is
pneumonia are S. pneumoniae, H. influenzae and S. aureus.
considered in the criteria for AIDS in children. In absence
In children with severe immunosuppression and hospital-
of antiretroviral therapy, nearly 20% of HIV-infected
acquired infections, gram-negative organisms, such as,
children developed LIP. The etiology and pathogenesis
Pseudomonas aeruginosa gain importance. Clinical features
of LIP are not well understood, but include: Exaggerated
in HIV-infected children are similar to those in other immune response to inhaled or circulating antigens, and/
children. However, in severely immunocompromised
or primary infection of the lung with HIV, Epstein-Barr
children, the signs may be subtle. Often, the response to virus (EBV), or both. LIP is characterized by nodule
therapy is slow and the relapse rates are high. Bacteremia formation and diffuse infiltration of the alveolar septa by
may be more common, seen in up to 50%. lymphocytes, plasmacytoid lymphocytes, plasma cells and
Choice of antibiotics is based on local patterns of immunoblasts. There is no involvement of the blood
etiologies and susceptibilities. An appropriate choice is vessels or destruction of the lung tissue. Children with
the combination of a broad-spectrum cephalosporin and LIP have a relatively good prognosis.
an aminoglycoside. In areas with large proportion of LIP is usually diagnosed in children with perinatally
MRSA, vancomycin, clindamycin, linezolid or other ~rugs acquired HIV infection when they are older than 1 year of
D
may be used. Children with non-severe pneumorua ~an age. Most children with LIP are asymptomatic. Tachypnea,
be managed as out-patients using a seco.nd or ~ thir~ cough, wheezing and hypoxemia are in children with
generation cephalosporin or coamoxiclav. Sm~e P. J1rov~c11 severe features; crepitations are uncommon. Clubbing is
pneumonia cannot be excluded i~ most ch~ldren with present in advanced disease. These patients can progress
severe respiratory symptoms, cotnmoxazole is also used to chronic respiratory failure. Long-standing LIP may be
unless another diagnosis has been made. associated with bronchiectasis. The presence of a
Tuberculosis is a common medical concern. Co-existent TB reticulonodular pattern, with or without hilar
and HIV infections accelerate the progression of both lymphadenopathy, that persists on chest radiograph for
diseases. HIV-infected children are more li~ely to have 2 months or greater and that is unresponsive to
extrapulmonary and disseminated tubercul?sis; the ~ourse antimicrobial therapy is considered presumptive evidence
is also likely to be more rapid. The overall risk of acti~e TB of LIP. A definitive diagnosis is made by histopathology.
in children infected with HIV is at least 5- to 10-fold ~gher Early disease is managed conserva.tively. ~he.effect ~f
than in children not infected with HIV. The duration of antiretroviral agents is limited. Steroids are indicated, if
antitubercular therapy in patients is same as that f~r not- children with LIP have symptoms and signs of chronic
HIV infected; a few children may need pr~longati?n of pulmonary disease, clubbing and/ or hypoxemia.
treatment to 9-12 months. Close follow-up is ess~r:itial to Treatment includes an initial 4- to 12-week course of
diagnose non-response or drug resistance. Rifan:1picm may prednisolone (2 mg/kg/ d) followed .by taper~? to low
show drug interactions with some antiretroviral agents dose medication, using oxygen saturation and clinical state
(nevirapine, protease inhibitors). as guide to improvement.
.
V 1ral . .
mfectwns c h'1efl y respira
· tory syncytial virus ./ Gastrointestinal Diseases
·
influenza '
and param . fl uenza vuuse
· s, often result
. m
symptomatic disease. Infections with ~denovirus ~nd Multiple microbes can cause gastrointestinal dise~se,
measles virus might result in seno~s. s~que. ae. including bacteria (Salmonella, Campt;lobacter,.My~obacteru~:
Disseminated CMV is a known opportunistic infection, avium intracellulare complex), protoz?a (Giardia, Isospo '
but pneumonia caused by the virus is rare. Cryptosporidium, microsporidia), viruses (CMV, HSV,
Ill 228
rotavirus) and fungi (Candida). Protozoa! infections are manifestation; polyuria, oliguria, and hematuria have als0
severe and can be protracted in children. Children with been observed. Hypertension is unusual.
Cryptosporidizmz infestation can have severe diarrhea
leading to hypovolemic shock. AIDS enteropathy, a Diagnosis
syndrome of malabsorption with partial villous atrophy All infants born to HIV-infected. mothers test antibody.
not associated with specific pathogens, is the result of positive at birth because of passive transfer of maternal
direct HIV infection of the gut. HIV antibody across the placenta. Most uninfected infants
Chronic liver inflammation is relatively common in lose maternal antibody between 6 and 12 months of age.
HIV- infected children. In some children, hepatitis caused As a small proportion of uninfected infants continue to
by CMV, hepatitis B or C viruses, or MAC may lead to have maternal HIV antibody in the blood up to 18 months
liver failure and portal hypertension. It is important to of age, positive IgG antibody tests cannot be used to make
recognize that several of the antiretroviral drugs such as a diagnosis of HIV infection in infants up to this age. In
didanosine, and protease inhibitors may also cause children >18 months old, demonstration of IgG antibody
reversible elevation of transaminases. to HIV by a two or three reactive enzyme immunoassay
Pancreatitis is uncommon in HIV-infected children. (EIA) and confirmatory test (e.g. Western blot or
This may be the result of drug therapy, e.g. didanosine, immunofluorescence assay) can establish the diagnosis of
lamivudine, nevirapine, or pentamidine. Rarely, opportu- HIV infection. While serologic tests were commonly used
nistic infections, such as MAC or CMV, may be responsible in the past, tests that allow for earlier definitive diagnosis
for acute pancreatitis. have replaced antibody assays as the tests of choice for
the diagnosis of HIV infection in infants.
Neurologlc Diseases Specific diagnostic assays, such as HIV proviral DNA
The incidence of central nervous system (CNS) involve- or RNA PCR, HIV culture, or HIV p24 antigen are useful
ment in perinatally infected children may be more than for diagnosis of young infants born to HIV-infected
50% in developing countries but lower in developed mothers (Fig. 11.11). By 6 months of age, the HIV culture
countries, with a median onset at about one and a half and/or PCR identifies all infected infants, who are not
years of age. The most common presentation is progressive having continued exposure due to breastfeeding. HIV
encephalopathy with loss or plateau of developmental RNA PCR is the preferred virological assay in developed
milestones, cognitive deterioration, impaired brain growth countries. IDV culture has similar sensitivity to HIV RNA
resulting in acquired microcephaly, and symmetric motor PCR; however, it is more technically complex and
dysfunction. CNS infections: Meningitis due to bacterial expensive, and results are often not available fo r 2-4
pathogens, fungi such as Cn;ptococc11s and a number of weeks. The p24 antigen assay is less sensitive than the
viruses may be responsible for the clinical features. CNS other virological tests. Fig. 11.11 shows the algorithm for
toxoplasmosis is exceedingly rare in young infants, but diagnosis of HIV infection in infants. The national program
may occur in HIV-infected adolescents; the overwhelming (Early Infant Diagnosis) now uses HIV total nucleic acid
Cardiovascular Involvement
Cardiac abnormalities in HIV-infected children are
(RNA + proviral DNA) PCR test on dried blood spot
samples; positive tests need confirmation with HIV PCR
test on another sample.
Management
common, persistent, and often progressive; the majority
is subclinical. Left ventricular structure and function The management of HIV-infected child inc ludes
progressively may deteriorate in the first 3 years of life, antiretroviral therapy, prophylaxis and treatment of
resulting in subsequent persistent cardiac dysfunction and opportunistic and common infections, adequate nutrition
increased left ventricular mass. Children with encephalo- and immunization. Decisions about antiretroviral therapy
pathy or other AIDS-defining conditions have the highest (ART) for HIV-infected patients were earlier based on the
rate of adverse cardiac outcomes. Resting sinus tachy- magnitude of viral replication (i.e. viral load), .~D~
cardia has been reported in up to nearly two-thirds and lymphocyte count or percentage and clinical cond1~on
marked sinus arrhythmia in one-fifth of HIV-infected The current World Health Organization guidehnes
children. Gallop rhythm with tachypnea and hepato- recommend ART for all children irrespective of the
splenomegaly appear to be the best clinical indicators of immunologic or clinical stage.
congestive heart failure; anticongestive therapy is Availability of antiretroviral therapy has transform~
generally very effective, especially when initiated early. IDV infection from a uniformly fatal condition to a chro~c
infection, where children can lead a near normal I~·
Renal Involvement Current therapy does not eradicate ~e virus ~d c:ure fo~
Nephropathy is an unusual presenting symptom of IDV child; it rather suppresses the virus replication us
infection, more commonly occurring in older symptomatic extended periods of time. The ~ee m~ ~~ups of~,
children. Nephrotic syndrome is the most common are nucleoside reverse transcnptase inhibitors (NR
I
---
Infections and Infestations 229 -
Positive Negative
Positive Negative
i
Continue cotrimoxazole; Repeat HIV-1 PCR (DBS)
start antiretroviral therapy; at 6 months or earlier, if the child
continue breastfeeding is symptomatic
t Positive Negative
J
+ +
Establish definitive diagnosis at 18 months, by HIV antibody tests (3 rapid tests) J
Fig. 11.11: HIV diagnosis in children < 18 months with DNA-PCR. DBS dried blood spot
Protease Inhibitors
Amprenavir 4-16 yr and <50 kg: 22.5 mg/kg q 12 hr (oral solution);
20 mg/ kg q 12 hr (capsules)
I
>13 yr and >50 kg: 1200 mg q 12 hr (capsules)
lndinavir 500 mg/m2 q8 hr; >13 yr: 800 mg q8 hr Hyperbilirubinemia, stones
Lopinavir/ ritonavir 7-15 kg: 12 mg/kg lopinavir; 3 mg/kg ritonavir q 12 hr with Diarrhea, fatigue, headache, nausea;
15-40 kg: 10 mg/kg lopinavir; 2.5 mg/kg ritonavir q 12 hr increased cholesterol and triglycerides
food >12 yr: 400 mg lopinavir; 100 mg ritonavir q 12 hr
Nelfinavir <13 yr: 50-55 mg/ kg q 12 hr Diarrhea, abdominal pain
>13 yr: 1250 mg q 12 hr (max: 2000 mg)
Ritonavir <13 yr: 35Q-400 mg/m 2 q 12 hr (start dose: 250 mg/m 2) Bad taste, vomiting, nausea, diarrhea,
> 13 yr: 600 mg q 12 hr (start dose: 300 mg) rarely, hepatitis
Saquinavir 50 mg/kg q 8 hr Diarrhea, headache, skin rash
> 13 yr: 1200 mg q 8 hr soft gel capsules
symptomatic HIV-infected children should not be given to the onset of labor and rupture of membranes), and
OPVand BCG. complete avoidance of breastfeeding.
Prevention of Mother-to-Chlld Transmission (MTCT) Antfretrovfrol Drug Regim ens for Pregnant Women
. 1·ral
The risk of MTCT can be re duced to under 2% by For all HIV-infected pregnant women, antiretrov.
interventions that include antiretroviral therapy given to therapy is indicated. The r ecommended regimen 15 ~
women during pregnancy and labor and antiretroviral combination of zidovudine (AZT), lamivudine (3TC) an
prophylaxis to the infant in the first week of life, obstetrical nevirapine (NVP) or efavirenz (EFV) during antep~rtull'~
interventions including elective cesarean delivery (prior intrapartum and postpartum period; EFV-based regilllen
Infections and Infestations I 231 -
should not be newly-initiated during the first trimester of leads to frequent antigenic "drifts" (seen in both A and B)
pregnancy. The ART regimen should be started as early when there is minor change in antigenicity and "shifts"
as possible. (seen only in A) where there is major change in
antigenicity. The phenomena of antigenic change lead to
,Antlretrovlral Regimens for Infants Born to evolution of new viruses, which result in annual outbreaks
HN-lnfected Mothers and occasionally pandemics. The novel HlNl pandemic
If ~other receive~ triple ~rug ART during pregnancy and occurred due to emergence of a new swine origin influenza
entire breastfee~mg, th~ infant should receive daily AZT virus H1Nl which was pathogenic to humans and capable
or NVP from birth until 6 weeks of age (irrespective of of rapid human-to-human transmission and to which there
feeding). was no pre-existing immunity. It is estimated that the
novel HlNl pandemic between 2009 and 2010 caused
/ntrapartum Interventions 18,000 deaths globally (2000 in India) with case fatality
Artificial rupture of membranes should be avoided unless rates ranging from 0.0004% to 1.5% (0.83% in India). The
medically indicated. Delivery should be by :1ective pandemic strain then became endemic and caused another
cesarean section at 38 weeks before onset of labor and epidemic in 2015 in India with 30000 cases and 2000
rupture of membranes. Procedures increasing exposure deaths. The currently circulating influenza virus strains
of child to maternal blood should be avoided. are H3N2, pandemic HlNl and influenza B.
Avian HSNl commonly referred as bird flu is a highly
Breastfeeding pathogenic strain of influenza virus that infects and kills
The risk of HIV infection via breastfeeding is highest in humans in close contact with diseased birds but has not
the early months of breastfeeding. Factors that increase acquired pandemic potential due to limited human-to-
likelihood of transmission include detectable levels of HIV human transmissibility.
in breast milk, presence of mastitis and low maternal CD4+ Influenza is transmitted from person to person through
T cell count. Exclusive breastfeeding has been reported to airborne droplet spread or through contact. The portal of
carry a lower risk of HIV transmission than mixed feeding entry is the respiratory tract and the virus attaches itself
and risk of mortality in non-breastfed infants in resource to the respiratory epithelium through hemagglutinin, the
limited settings is increased. Currently, exclusive main virulence factor. The incubation period is 1-3 days
breastfeeding is recommended during the first months of and the period of infectivity is usually 7 days after illness
life. WHO recommends that the transition between onset and sometimes longer in those with severe disease.
exclusive breastfeeding and early cessation of The attack rates are highest in children and young adults.
breastfeeding should be gradual and not an "early and In temperate climates, there is a clear defined influenza
abrupt cessation". season in fall and winters, but in tropical countries like
India, it occurs throughout the year with peak during the
Suggested Reading monsoons.
• WHO/UNAIDS. AIDS epidemic update Dec 2016.
• World Health Organization. Consolidated guidelines on the use
of antiretroviral drugs for treating and preventing HIV infection,
2nd edn. WHO, Geneva, 2016.
• NACO. Pediatric antiretroviral therapy guidelines, 2013 http:/ I
Clinical Features
In most individuals, influenza is a minor illness charac-
terized by a combination of fever, runny nose, sore throat,
I
cough, body ache, headache, abdominal pain, diarrhea and
naco.gov.in/sites/default/files/Pediatric_14-03-2014.pdf.
vomiting. The illness may have a biphasic course.
Influenza Recovery usually occurs within a week. It is sometimes
difficult to differentiate from common cold. Asymptomatic
The influenza virus is capable of causing disease in and subclinical infections are also very common.
humans, birds and animals. Influenza has recently gained A small proportion of individuals (less than 1%) can
more prominence owing to the 2009 novel HlNl have complications and severe disease. The risk of
pandemic. complications is higher at extremes of age (children below
2 and the elderly), pregnant women and those who have
Epidemiology just delivered, those with underlying comorbidities such
The influenza virus is an RNA virus of the Orthomyxo- as any chronic neurologic I metabolic/ cardiac I
Viridae family. Influenza A and Bare the two types that pulmonary /renal disease, those who are immuno-
cause human disease. Influenza A is further classified into comprornised and those with severe asthma. In the novel
subtypes based on the two surface proteins-hemagglutinin HlNl epidemic, the elderly were spared due to pre-
(Ii) and neuraminidase (N). Influenza Bis classified into existent immunity and morbid obesity emerged as an
two distinct lineages-Yamagata and Victoria but not into important risk factor.
~ubtypes. Influenza has a highly segmented genome that The most dreaded complication of influenza is
is prone to frequent mutations and reassortment. This pneumonia with acute respiratory distress syndrome,
- 232 -------------------------~E~s~s~e~n~tl~a~l~P!ed~l~a~tr~lc~s~--------------------~-----~
respiratory failure and sometimes shock and renal failure. For Patients who present
· ·
with symptoms of sev
t' ' I <'r~
As many as 30% of these patients have bacterial coinfection illness or who have comphcah~ns,.a~ Lv1r~ treatment Wllh
with S. pneumoniae and S. aureus. Progression is very rapid oseltamivir should be starte wit. out elay', An effort
Id be made to rule out• other illnesses w1Lh slni'I
and most patients require ventilator support over the next S h OU . h , '•lr
24 hours. Occasionally, other complications such as symptomatology. In pah:n.ts. w1~ signs of lower
encephalitis, seizures, quadriparesis and myocarditis have respiratory involvemen~, ant1b1ot~cs hke coamoxyclav or
been reported. Complications usually set in by day 4 or 5 cephalosporins (cefurox1me, ceftriaxone or cefpodoxim~)
of illness. The red flag symptoms are persistent high fever should be used as bacterial coinfections are common.
of more than 3 days duration, reappearance of fever after
initial defervescence, breathlessness, dyspnea, tachypnea, Prevention
hemoptysis in older children and adolescents, extreme Vaccination is the most effective preventive strategy and
weakness, poor oral intake and altered sensorium. is discussed further in Chapter 10. Chemoprophylaxls
with oseltamivir is also effective in preventing influenza
Diagnosis but is not routinely recommended due to risk of resistnnce.
Influenza is primarily a clinical diagnosis. The complete Household transmission can be reduced by good
blood count may show leukopenia and thrombocytopenia. ventilation in the room, proper hand hygiene and
Diagnosis is confirmed by antigen detection or PCR on adherence to cough etiquettes by the index case. School
throat or nasopharyngeal swabs. PCR-based tests are fairly children show one of the highest infection rates and
sensitive and very specific but are of limited use in routine outbreaks are common in school. For reducing
clinical practice. Specific therapy may thus begin before transmission in schools, the classrooms should be kept
results become available. If the test is negative, therapy well ventilated, children should be trained in hand
cannot be discontinued as sensitivity is only 60-70% and hygiene and cough etiquettes and sick children should be
even lower, if the sample is not properly collected. prohibited from attending school till they are afebrile.
Molecular diagnosis of influenza should be restricted to Temporary school closure may be considered during a
hospitalized patients with severe disease when a defirlitive massive pandemic. In order to prevent nosocomial
diagnosis helps in tracking the severity of the outbreak. transmission, standard infection control precautions
Since the symptoms and lab findings of severe flu including droplet isolation and routine immunization of
overlap those of other infections such as malaria, dengue, health care workers are recommended.
enteric fever, viral hepatitis and leptospirosis, it is
important to conduct appropriate laboratory tests to Suggested Reading
exclude these illnesses. • World Health Organization. Influenza update. www.who.int
• Kumar B, Asha K, Khanna M, et al. The emerging influenza virus
Treatment threat: Arch Virol 2018; 163:831-44.
Definitive treatment of influenza is with M2 inhibitors
I
Zika Virus
(amantadine, rimantidine) or neuraminidase inhibitor
drugs (oseltamivir, zanamivir). The duration of therapy is Zika is an RNA flavivirus closely related to the dengue
5 days. These drugs reduce duration of symptoms, risk of and chikungunya viruses which has recently assumed
complications and death. Though they are most effective, if prominence due to its association with newborn
given within first 48 hours, they are useful even if given microcephaly.
later. The pandemic HlNl strain and most current seasonal
flu strains are resistant to the M2 inhibitors. Oseltamivir is Epidemiology
the first-line drug and zanamivir is used in those with The virus was first identified in a rhesus monkey in the
oseltamivir-resistant virus. Oseltamivir is well tolerated Zika forest of Uganda in 1947 with only 13 human cases
with occasional GI and neurological side effects. diagnosed till 2007. Since then, large outbreaks have
For any patient presenting with influenza-like illness, happened in the Pacific islands of Micronesia, French
the treatment strategy depends on two factors: The Polynesia and New Caledonia. A very large outbreak was
severity of illness and the likelihood of complications. In reported in Brazil in 2015 with almost a million cases. The
patients with mild disease who are not at risk for virus has since spread worldwide including Asia. The
complications, only symptomatic treatment is indicated. WHO has declared it as a public health emergency ~f
Antibiotics and antivirals should not be prescribed. International Concern. No cases have been reported J1l
Patients should be counselled about the red flag signs and India as yet; but India is at high risk for introduction of
asked to seek medical care in the event these occur. These the virus due to presence of the Aedes aegypti mosquito.
pati~ts should be asked to stay at home till they are The virus is transmitted primarily by the bite of Ae:J6
afebrile to prevent disease transmission to others. Patients aegypti. Other routes of transmission include vertical
who ~e. at high risk for complications should be started transmission from mother to child, sexual and possibly
on antivual therapy irrespective of the severity of disease. through blood transfusion.
Infections and Infestations I 233 -
cllnfcal Features and Complications weakness, nausea, vomiting, abdominal pain and joint ~d
muscle aches. This is followed by bleeding from multiple
?vfany infections are asymptomatic. Clinical disease is
sites and multiorgan failure, with fatality of 60%.
characterized by low grade fever with arthralgia, myalgia,
rash, conjunctivitis and lymphadenopathy. Sympto- Diagnosis and Treatment
xnatology resembles dengue and chikungunya except that
rash and conjunctivitis are more prominent than the other There is leukopenia and thrombocytopenia. Definitive
two illnesses. diagnosis is by antigen detection, IgM ELISA: polymer~se
chain reaction and viral isolation. Treatment 1s supportive
There are two major complications of zika infection.
The first is acute neurologic syndromes such as Guillain- and symptomatic. Several novel therapies including
Barre syndrome, myelitis and meningoencephalitis. serum of infected patients who have recovered from
However, more importantly are the teratogenic effects disease and nucleic acid-based therapies are under
with an incidence of 30% in some cohort studies in Brazil. evaluation.
Infections in the first trimester and sometimes in the Prevention
second trimester are associated with abortions,
intrauterine deaths and stillbirths, microcephaly (13%) and Prevention centers around strict isolation of infected cases,
ocular abnormalities. safe burial practices and avoiding consumption of bush
meat. Candidate vaccines are undergoing trials.
Diagnosis
Suggested Reading
Diagnosis in the first seven days is by performing an RT
PCR in blood and after seven days is by IgM MAC ELISA.
• Richards GA, Baker T, Amin P, et al. Ebola virus disease. J Crit
Care 2018; 43:352-55.
ELISA can demonstrate cross-reactivity with other
flaviviruses. Emerging Viruses in India
Treatment
Crimean-Congo hemorrhagic fever (CCHF) vints is an
RNA virus of the Bunyaviridae family normally infecting
There is no specific treatment and care is symptomatic cattle and occasionally transmitted to humans by infected
and supportive. Prevention revolves around avoiding ticks. The virus is highly contagious and human-to-human
travel to zika-afflicted areas especially by pregnant transmission in household and hospital setting is not
women, and vector control. Candidate vaccines are in uncommon. Outbreaks of CCHF have been reported from
development. various countries including Pakistan. It was first reported
from India in 2011 from Gujarat. The presentation is that
Suggested Reading of a viral hemorrhagic fever with fever, body pain, head-
• Bhardwaj 5, Gokhale MD, Mourya DT. Zika virus: Current concerns ache, profuse bleeding, leukopenia, thrombocytopenia,
irl India. Indian J Med Res 2017; 146:572-75. altered liver functions, deranged coagulation parameters,
Ebola Virus
The Ebola virus is an RNA virus belonging to the family
Filoviridae first described in 1976 near the Ebola river in
Democratic Republic of Congo. Several outbreaks of
rhabdomyolysis and renal failure. The disease mimics
dengue with salient differences being early and more rapid
platelet fall and rhabdomyolysis. Diagnosis is by specific
PCR. Treatment is supportive; early administration of
ribavarin is beneficial. Strict isolation of affected patients
ID
hemorrhagic fever have been reported with high mortality. is crucial to prevent nosocomial transmission.
Hantaviruses, rodent-borne viruses, cause two important
Epidemiology clinical syndromes: Hemorrhagic fever and renal
The Old World Fruit Bat is the natural reservoir of Ebola syndrome (HFRS) in Europe and Asia including India and
virus. Infection is transmitted to wild or farm animals hantavirus cardiopulmonary syndrome in America.
(chimpanzees, pigs, monkeys) and humans through direct Rodents are natural hosts and humans acquire infection
contact with bats or consumption of plants/products by inhalation of aerosols/ contact with water contaminated
contaminated with bat feces or body fluids. Humans can by rodent excreta or saliva. In India , HFRS and
also be infected by direct contact with infected animals or asymptomatic hantavirus infection has been reported from
handling or consuming meat of infected animals. Human- Tamil Nadu. The disease presents as a febrile illness with
to-human transmission to family members, caretakers and body pain, headache, thrombocytopenia, elevated liver
health care workers can occur through close contact or enzymes, bleeding and renal failure. Leukocytosis with
handling the fluids of infected patients. shift to left differentiates it from dengue. Diagnosis is by
specific IgM antibodies. Leptospirosis is a close
CllntcoJ Features differential. Coinfections of leptospirosis and hantavirus
The incubation period varies from 2-21 days; initial have also been reported. Treatment includes ribavarin and
8 Yffiptoms are non-specific and consist of fever, headache, supportive care.
B1oont1AI PodfatrfCI
I
erythematous skin rash, hepatic derangement, sensorial of pediatric infections particularly pneumonia. It is
changes and high mortality. Disseminated staphylococcal estimated that 50% of deaths due to severe pneumonia
disease is seen in previously healthy children and are caused by pneumococcus.
characterized by suppurative staphylococcal infections at
multiple sites either together or serially. Etlopathogenesis
CONS are usually pathogens of lower virulence than S. Pneumococcus is a gram-positive diplococcus with a thick
aureus. Since they colonize the skin, they are often cultured polysaccharide capsule. This capsule is the most important
as contaminants, if blood cultures are not collected by virulence factor and determines the various serotypes of
aseptic techniques. They are commonly implicated in the pneumococcus. Almost 90 serotypes of pneumococcus
bacteremia in low birth weight babies or in those with
exist but only a handful cause disease. Serotypes l, 3, 4, 5,
central venous catheters, subacute infective endocarditis, 6A and 6B, 9V, 14, 18C, 19A, 19F and 23 commonly cause
CNS shunt infections, infections associated with peritoneal
human disease and are incorporated in the vaccines.
dialysis catheters and prosthetic joints, urinary tract Pneumococci colonize the nasopharynx; these rates are
infections and postoperative surgical site infections.
highest in young children. Risk factors for disease include
extremes of age, splenic dysfunction, immunodeficiency
Treatment
especially HIV, any chronic disease and CSF leaks.
The most important treatment strategies are surgical
drainage and antibiotics. Antibiotic therapy of staphylo- Cl/nlcal Features
coccal infections has become complicated due to evolving Pneumococcal infections are distributed like a pyramid,
resistance in staphylococci. More than 90% of the current the base being non-invasive disease such as otitis media,
day organisms are resistant to penicillin due to production sinusitis and pneumonia and the apex comprising of
of a beta lactamase or penicillinase that destroys the beta invasive disease like severe pneumonia, bacteremia and
- 236 Essential Pediatrics
meningitis. It is estimated that for every 1000 cases of otitis Suggested Reading
media, there is 1 case of meningitis. Other less common , Global pneumococcal disease and vaccine, www .cdc.gov I
invasive diseases due to pneumococci are osteomyelitis, pneumococcal/global.html .
septic arthritis, cellulitis and peritonitis. , Maraga NF. Pneumococcal infections. Ped1atr Rev 2014; 35:299-310.
Pneumococcus is responsible for 30% of all acute
Diphtheria
bacterial meningitis and is associated with high rate of
complications like subdural empyema, morbidity and Diphtheria is an acute bacteri~l infe~tion c~used by gram.
mortality. Pneumococcal bacterernia presents usually as positive bacillus Corynebacterium dtphtherzae. Though the
fever without focus in infants and children below 3 years, incidence of diphtheria has decreased remarkably
and needs aggressive therapy. Pneumococcal pneumonia following increasing immunization, cases do occur in
has a lobar distribution with necrosis and empyema being unvaccinated children and adults who have lost their
common complications. immunity.
Etlopathogenesls
Diagnosis
The secretions and discharges from infected person or
The gold standard for diagnosis is culture. Low culture carrier are the main source of infection. The infection is
yields are responsible for under recognition of pneumo- transmitted by contact or via droplets of secretion. The
coccus as a common pathogen. Pneumococcus unlike portal of entry is commonly the respiratory t~act. ~e
Salmonella is difficult to culture, especially if antibiotics incubation period of the disease is 2-5 days. C. d1phthenae
have been administered. Special media containing sheep proliferates and liberates powerful exotoxin which is the
blood are required and delays in transportation and principal cause of systemic and local lesions. The exotoxin
improper storage further reduce recovery. In pneumonia, causes necrosis of the epithelial cells and liberates serous
isolation rates from blood are low, and the ideal sample and fibrinous material which forms a grayish white
of lung aspirate cannot be obtained in routine clinical pseudomembrane which bleeds on being dislodged. The
practice. Other tests useful in diagnosis are Gram stain surrounding tissue is inflamed and edematous. The organs
(Fig. 11.13), latex agglutination tests in CSF and pleural principally affected by the exotoxin include the heart,
fluids and recently PCR. kidney and myocardium.
l),.
.. • • I
•
"• ••
respiratory distress. Diphtheritic lesions may occasionally
also be found in skin and conjunctiva .
The commonest complication is respiratory failure due
to occlusion of the airways by the membrane. Myocarditis
..
1.
'
.'
"'
l,· • '
'.9 #
generally occurs by second week of illness and can lead
to symptoms of congestive cardiac failure, arrhythmias
and sudden death. Neurological complications include:
. .... -a....,
I.,~',. .
• -t (i) Palatal palsy, which occurs in second week and is
• ' 1 clinically m anifested by n asal twan g and nasal
t regurgitation; (ii) ocular palsy in third week; (iii) loss of
accommodation, manifested by visual blurring and
I 1
! J inability to read; (iv) generalized polyneuritis occurs by
Fig. 11.13: Gram stain of pus showing abundant gram-positive third to sixth weeks of illness. Renal complications include
dlplococcl, pneumococcl oliguria and proteinuria.
Infections and Infestations I 237 .
I
Features
Bed rest is advocated for two to three weeks. Children
should be monitored for airway obstruction and managed; T~e. incubation ~eriod of the disease is 7-14 days. The
tracheostomy may be required in some cases. Sudden cllllical presentation can be divided into three stages.
exertion should be avoided and changes in rate and The catarrhal phase lasts for 1-2 weeks and is the most
rhythm of heart should be looked for. Children with infectious. The initial manifestations are indistin!ruishable
palatal palsy should be fed by nasogastric feeding. from upper respiratory tract infections. The ~hild has
Generalized weakness due to polyneuritis is treated as cou?h, coryza with little nasopharyngeal secretions.
for poliomyelitis or Guillain-Barre syndrome. Unlike the upper respiratory infections, the cough does
not improve in a few days but becomes more severe and
Prevention and Control frequent "".ith the passage of ~e. Though the cough may
The patient should be isolated until two successive not be.typically paroxysmal m early stages, it tends to be
cultures of throat and nose are negative for diphtheria annoymg and frequent at night. The paroxysmal nature
bacillus. All contaminated articles from discharges should of the cough is suspected towards the latter part of this
be disinfected. All household/ other contacts should be phase.
observed carefully for development of active lesions, The paroxysma.l sta?e lasts for 2-6 weeks in which cough
c~tured for C. diphtheriae and given chemoprophylaxis pro~esse.s to ep1sod1c paroxysms of increasing intensity
With oral erythromycin for 7 days or single dose benzathine ~ndmg with high-pitched inspiratory whoop. The whoop
Penicillin. Previously immunized asymptomatic patients is produced by the air rushing in during inspiration
should receive a booster dose of diphtheria toxoid. Those through th: h~lf-open glottis. The whoop may not always
not fully immunized should receive immunization for be present m infants who present with apneic or cyanotic
their age (Chapter 10). spells. The child coughs up thick tenacious mucus. The
paroxysms of cough may occur frequently and terminate
Suggested Reading by vomiting. Repeated thrusting of tongue over the teeth
• Clarke KEN. Review of the epidemiology of diphtheria: 2000-16. causes ulceration of the frenulum of the tongue.
WWw.who.int Paroxysms of cough are precipitated by food, cold air and
- 230 E11ont111I Pediatric•
mid lh1uld ~. In lnfonlH ~:1 111011th11, lhlfl tilllfW mny lrn suggosted Reading
conHldcmhly pn1lo11Hcd. • Yeung J<HT, Duclos P, Nelson EAS, Hutubessy RCW. An
In th~ t'1m1 111/r~Cl'lll 11/uWl', the lntmv1lty nnd pnroxyRmFI of the global burden of pertussis in children younger than su::tt
of \'.nugh <lt•nt•~su grndunlly over J....i wcck11, Thu vomiting Lancet fnfcct Dhi 2017; 17:974-80. r1.
1
tials for pertussis include adenoviral infections,
endobronchial tuberculosis, extrinsic compression of and the liver and spleen. It multiplies in the reticulo-
airways by lymph nodes, inhaled foreign body and endothelial system and after incubation period varying
reactive airway disease. from 7-14 days spills into the bloodstream and is widely
disseminated, especially to liver, spleen, bone marrow,
Management gallbladder and Peyer patches of the terminal ileum. ThiS
marks the onset of clinical manifestations of enteric fever.
General measures include providing adequate nutrition Infection leads to local and systemic immune responses,
and hydration and avoiding factors aggravating cough. which are, however, inadequate to prevent relapse or
Macrolides including erythromycin, azithromycin or reinfection.
clarithromycin are the drugs of choice. Antibiotics
terminate the respiratory tract carriage of B. pertussis thus Cl!nlcal Features
reducing the period of communicability but do not shorten
There is no appreciable difference between the manifestaf
the course of illness. Nebulization with salbutamol is
tions of typhoid and paratyphoid fever. The halhnark 0
sometimes effective in reducing bronchospasm and
enteric fever is fever which starts as a low grade fever
controlling bouts of cough. Cough suppressants and and then shows stepwise increase peaking to as high as
antihistaminic agents should be avoided.
103-104°C by the end of the first week. This patterI1
differentiates it from viral fever where the peak is usuaIIY
Prevention
at the onset of fever. With fever, there is associated malaiSe
. ed,
Chemoprophylaxis with erythromycin is recommended dull headache, anorexia, nausea, poorly loca 1iz
for close family contacts especially children <2 years of abdominal discomfort, mild cough and malaise. Th.er~
age. Non-immunized and partially immunized contacts may be diarrhea; constipation in children is rare. PhY51c~
should be vaccinated (Chapter 10). findings are unremarkable with the exception of a coate
,. . .
Infections and Infestations I 239 •
tongue, tumid abdomen and sometimes hepatospleno- drops to 40% in the 4th week. Its overall sensitivity is 60%,
rnegaly. The ras~ described in Western textbooks is seldom which reduces to 20-40% after antibiotics. Salmonella is
or never s~en m I~dian subjects. Infants and young an easy organism to culture and use of bile broth media
chil~ren with ~nten~ fever may have diarrhea as a pre- and automated culture systems such as BACTEC improve
donunant manifestation or a short-lasting undifferentiated recovery. Sufficient blood should be collected (10 ml in
febrile illness. In the absence of treatment, fever may adults and 5 ml in children) and a blood: media ratio of
continue for ~ weeks followed by natural remission or 1:5 should be maintained. The use of clot culture methods
by development of complications. does not significantly improve recovery rates. Bone
marrow cultures have higher yield as compared to
complications
peripheral blood cultures as Salmonella is a pathogen of
Tue co~onest ~testinal complications are bleeding or the reticuloendothelial system and should be sent, if a bone
perforation seen m the 2nd or 3rd week of illness in marrow examination is done as part of work-up for
10-lS:'o a~ult patients, ~ut less frequently in children. pyrexia of unknown origin. Owing to very low recovery
Bleeding is due to erosion of a necrotic Peyers patch rates, stool cultures and urine cultures are not
through the wall of a vessel and is usually mild but can, recommended. Antimicrobial susceptibility testing of the
sometimes, be life-threatening. Perforation is a dreaded isolate is important in the era of multidrug resistance.
complication manifesting as acute abdomen, with high The Widal test detects presence of IgG and IgM
mortality unless appropriately treated. antibodies to H (flagellar antigen) of S. enterica var typhi
The term severe or complicated enteric fever is used and paratyphi A and B, and 0 (somatic antigen) common
for patients presenting with neurological complications to typhi and paratyphi A and B. Anti-0 titers are both
such as delirium, coma, obtundation, stupor or shock and IgG and IgM that rise and decline early, while anti-His
is associated with mortality rates as high as 50%. Other primarily IgG that rise and decline late in course of the
complications of include hepatic and splenic abscesses, disease. The conventional method of interpretation of the
hepatitis, cholecystitis, pneumonia, disseminated Widal test has been to demonstrate fourfold rise in
intravascular coagulation, psychosis, ataxia or meningitis. antibody titers in two samples. Since this is often not
The case fatality rate is less than 1 % in appropriately practical, a single titer of at least 1:160 for both 0 and His
treated cases but may be 10-20% in inadequately treated considered positive. Even with this compromise, the Widal
or complicated cases. test has several limitations. Sensitivity is low in the first
week of illness and in patients treated with prior
Relapse: Relapse may occur in 5-15% of treated cases,
antibiotics. Specificity is low owing to anamnestic
usually due to the organism with the same susceptibility
reactions, prior vaccination, cross-reactivity with other
as the original attack and is relatively a milder illness. Rate
of relapse is dependent on choice of drug therapy. It is
Enterobacteriaceae and subclinical infections in endemic
areas.
higher with beta lactams such as cefixime or ceftriaxone
Ill
as compared to quinolones and azithromycin.
Treatment
Carrier state: Although 5-10% adult patients may shed
Indications for inpatient treatment: Most cases of enteric
Salmonella in stool following an acute attack for up to
fever can be managed at home with oral antibiotics and
3 months, only 1-4% excrete bacilli for more than 1 year.
advice to seek medical follow-up in case of failure to
These individuals are potential sources of infection for
respond to therapy or development of complications.
family members and contacts and for the community, if Children with persistent vomiting, poor oral intake, severe
!hey are in occupations that involve f~od p~ocessing. Th~re diarrhea or abdominal distension usually require
is no data on carrier prevalence m children; routme intravenous (IV) antibiotics and IV fluids, necessitating
examination of stool following recovery from enteric fever admission to hospital.
is not recommended.
Antimicrobial susceptibility: The antimicrobial sensitivity
Diagnosis of S. typhi/paratyplzi has shown changes over the decades.
Leukocyte counts may be normal to low with ab~olute Though resistance to chloramphenicol was first noted soon
eosinopenia and neutrophilic predominance: Anemia and after its first use in 1940s, it was not until 1972 that
thrombocytopenia may occur in advanced illness. J?ere chloramphenicol-resistant typhoid fever became a major
may be mild elevation of transaminases to 2-3 hmes problem. Multidrug-resistant typhoid fever (MDRTF)
normal (SGOT being higher than SGPT). A v~ry high C::- became a common occurrence by the end of 1990s, with
reactive protein sometimes helps to differentiate entenc emergence of S. typhi simultaneously resistant to all the
from viral fevers, especially dengue. Ultrasound abdomen drugs that were used as first-line treatment (chloram-
shows mesenteric adenitis with splenomegaly. phenicol, trimethoprim, sulfamethoxazole and ampicillin).
The gold standard for diagnosis is blood culture. The Fluoroquinolones were introduced in the late 1980s and
5ensitivity is greatest in the first week at around 90% but early 1990s and produced very good results initially, but
- 240
-~~--------------~~--~E=s~s~e~n~tl~a~l~P!e~d~la~tr~lc~s::__~--------~~------------~
the past decade has see1\ a progressive increase in the Cefixime) especially if shorter duration of therapy 111 t
. fac ton'I y treated With''lt··I
Although relapses may b e satts
minimum inhibitory concentrations (MIC) of ciprofloxacin df . th 'h l 11o
in S. typl1i and paratypl1i and resistance rates to same drug as use ~r p~t~ry er?pty,daz1~ hrornyc1n I~
fluoroquinolones/nalidixic acid now approach 90%. the preferred drug smce l 1s associa e wit very 1 ,,~,
Thl~ lllnt•11s IH often blplu1slc. Jn the Initial or septicemic by dark field microscopy or immunofluorescence and
phoRo llrntlng 2-7 days, the onset ia .ibrupt with high grade cultures are not routinely available. However, it is now
fever with rlgnr1.4 and chllla, lethargy, severe myalgia, possible to diagnose the illness in the first few days by
Jwndnclw, JHHIHl!a, vomiting. Patient may have PCR in blood.
conjuncllvol ~uffuslun with photophobin and orbital pain, Leptospirosis should be differentiated from other
grncrnllzcd lymphadcnopathy and hepatosplenomegaly. febrile illnesses commonly seen in the monsoon season
Transient mnculopapular crythematous rash may be seen such as malaria, dengue, enteric fever, acute viral hepatitis
In <10'X, cnHcs. Hypotenslon with bradycardia and and hanta virus infections.
circulolory rnllnpsc is rnrcly seen. Some patients develop
acute rcsplrnlorr distress syndrome with respiratory Treatment
follurc. Most patients become asymptomatic within one Treatment should be initiated as early as possible. For
week.
severe leptospirosis, parenteral penicillin G (6-8 million
In some pnlicnts, after a brief asymptomatic phase, U/m2 /24 hr q 4 hr IV for 7 days) is the drug of choice.
the second phase, c~lled the immune or leptospiruric Ceftriaxone and IV tetracycline are also acceptable
pha~e, bcc.<>mcs manifest wherein Leplospira localize to alternatives. For oral treatment, amoxicillin and in children
various tissues. to cause tissue specific signs and above 8 years, doxycycline are preferred.
sympto.ms. In this phase, circulating autoantibodies to
Leptosp1m nrc present; organisms can no more be isolated Prevention
from blood or csr but persist in tissues like kidneys and Prevention entails avoidance of exposure to contaminated
aqueous humor. During the immune phase, some water. Single dose doxycycline or amoxicillin following
children mny develop nseptic meningitis or uveitis with exposure can also prevent illness.
recurrence of fever. Encephalitis, cranial nerve palsies,
paralysis and papilledema are rare manifestations. Suggested Reading
Central nervous system abnormnlities usually normalize • Rajapakse S, Rodrigo C, Balaji K, et al. Atypical manifestations of
within one week; mortality is rare. Jeptospirosis. Trans R Soc Trop Med Hyg 2015; 109:294-302.
In icleric leptospirosis (Wcil's syndrome) after the initial • Tullu MS, Karande S. Leptospirosis in children: a review for family
phase of fever, pntients develop severe hepatic and renal physicians. Indian] Med Sci 2009; 63:368-78.
dysfunction. Jaundice, hepatomegaly and tenderness in
right upper quadrant are usually detected. Splenomegaly Tetanus
found in 20°/., of cases. Non-oliguric renal failure with Tetanus is caused by the bacterium Clostridium tetani, a
azotemia mny develop, often during the second week of spore.forming, anaerobic, gram-positive, motile bacillus,
illness. All patients have abnormal urinary finding on
urinalysis in the form of hematuria, proteinuria and casts.
Hemorrhagic manifestations are rare but when present,
may include epistaxis, hemoptysis and gastrointestinal
and adrenal hemorrhage. Transient thrombocytopenia
found in human and animal feces. These spores are
widespread in the environment. From an estimated
80,000 deaths from neonatal tetanus in India in 1990, less
than 500 cases were reported in 2015 thus certifying India
as free of maternal/neonatal tetanus. Elimination of
I
may occur. Mortality is 5-15%. neonatal tetanus has been defined as less than 1 case of
neonatal tetanus per 1000 live births in every district of
Diagnosis the country.
Complete blood count shows anemia, leukocytos~s with
Pathogenesis
polymorph predominance and thromboc~topema. The
CRP is elevated and liver enzymes are nuldly elevated C. tetani is a non-invasive organism. The spores of the
with SGOT more than SGPT; CPK levels are high. In organism remain nonpathogenic in soil or contaminated
patients with Weil's disease, there is elevated se:um tissues until conditions are favorable for transformation
creatinine, deranged coagulation paramet~rs and direct into vegetative form. Transformation occurs in the
hyperbilirubinemia with elevated transammas~s. . presence of locally decreased oxygen reduction potential,
Specific diagnosis is established by se:olog1c testing, typically in devitalized tissue, in the presence of a foreign
microscopic demonstration of the organism, cul~ure or body, trauma and crush injury and suppurative infections.
PCR. Serologic diagnosis is possible afte~ 5 days ?f i~lness. Two types of toxins are produced by the organism,
The gold standard for serologic diagn~s1 s. •s the tetanolysin and tetanospasmin. Tetanospasmin is the main
microscopic agglutination test (MAT), which is only toxin responsible for the manifestations of the disease. It
available in reference centers. Commercial kits for binds to the neuromuscular junction at the site of injury,
serologic diagnosis include rapid tests and IgM E.L~SA but and undergoes retrograde axonal transport to reach the
these tests are often associated with cross·reactiv~ty and presynaptic nerve terminal where ~t prevents the rele~se
false positivity with other infections sue~ a~ entenc fe~er of inhibitory neurotransmitters glycine and GABA leading
and malaria. Demonstration of organism in tissues or unne to uncontrolled contraction of muscles.
• 242 Essential Pediatrics
Cllnlcol Features
Tctilnus mainly affects the unimmunized and partly
immunized individuals. Thediseasemayoccurin various
forms: Neonatal, generalized, localized, and cephalic. The
most common forms are generalized and neonatal
tetanus.
Gcmeralized tetanus has an incubation period of
approximately 8 days (range 2-14 days). However, the
disease may occur months after the initial injury. The
incubation period depends on the distance of the site of
injury from the central nervous system. The faster is the
onset of symptoms, the poorer is the prognosis.
Characteristically, there is descending paralysis, with
initial involvement of the jaw muscles. There is spasm of
Fig. 11.14: Neonatal tetanus (Courtesy: Dr Amarjeet Mehta
the masscters leading to trismus or lockjaw. Subsequent
involvement of the neck, back and abdominal muscles Jaipur)
occurs, soon involving the whole body. As the disease
progresses, minimal stimuli may lead to generalized Treatment
spasms, the hallmark of the disease and contribute to Most patients require intensive care management and
serious complications and eventually death. Typically, the good supportive care. The aims of treatment are ainvay
sensorium of the patient is preserved. There is difficulty maintenance, prevention of further toxin absorption,
in swallowing. Autonomic instability may occur, with relieving clinical features, e.g. spasms, controlling auto-
blood pressure fluctuations in the form of hypertension nomic instability and antibiotics. Airway management
or hypotension, diaphoresis and arrhytlunias. Recovery may require intubation and mechanical ventilation,
usually begins after 3 weeks and approximately takes four especially in severe cases and if the infant gets frequent
weeks. Recovery from tetanus occurs by sprouting new episodes of largyngeal spasms, apneic attacks or central
nerve terminals in the spinal cord leading to relaxation of respiratory failure. Neutralization of free toxin is done by
the contracted muscles. administering human tetanus im.munoglobulin; however,
antitoxin cannot dislodge the toxin already fixed to the
Neonatal tetanus is a major cause of mortality in nerve roots. The route of administration is intramuscular
developing countries. Pregnant women who are not or intrathecal. The usual dose is 500to1000 IU. Antibiotic
immunized against tetanus do not pass on protective therapy is needed to abolish the bacteria from the wound
antibodies to their babies. Infection results from unhygienic
site; commonly used agents are crystalline penicillin or
I
birth practices, most commonly when the umbilical cord is metronidazole.
contaminated at the time of cutting. Symptoms usually
appear by the third day after birth, never in the first two Spasms are precipitated by minimal stimuli, th~refore,
days of life and rarely after the age of two weeks. Excessive efforts should be made to avoid noxious stimuli including
unexplained crying followed by refusal of feeds and apathy bright lights, pain and loud noises. Relief of spasms is done
are the common initial symptoms. The baby develops ~sin? benzodiazepines. The most commonly used agent
progressive feeding difficulty, becomes rigid, develops is diazepam, either as an intermittent IV bolus or as
paralysis, and may develop opisthotonic posturing and continuous infusion. Diazepam prevents further spasn'\S
experience painful spasms. The mouth is kept slightly open by causing GABA-mediated central inhibition. It also
due to pull and spasm of the neck (Fig. 11.14). There is helps by reducing anxiety and promoting m uscle
generalized rigidity and opisthotonus in extension. Spasms relaxation. Other agents used for severe spasms include
?f larynx and. resi:>iratory muscles are characteristically p~curonium bromide. Autonomic instability is controlled
mduc~d ~y st~uli such as touch, noise and bright light, with the use of alpha and beta adrenergic blockers, and
resulting m epISodes of apnea and cyanosis. The case fatality IV magnesium.
is high (70-100%). All patients should receive a complete course of
immunization with tetanus toxoid once recovered, as the
Localized tetanus is less severe in comparison, and is disease does not induce protective antibodies.
characterized by rigidity and pain confined to the muscles
adjacent to the wound. It may lead to generalized tetanus Prognosis
later. I.n ~atients with isolated localized tetanus, the The disease has high mortality rate in spite of adequate
mortahty is less than 1%. Cephalic tetanus is a form of local supportive care, which may reach up to 50% in severe
tetanus, which occurs due to injury of the bulbar muscles, generalized tetanus and 90% in neonatal forn1. Th~
has a poor prognosis. 0
outcome depends on the incubation period, the site
Infections and Infestations I 243 -
I
epidemiology of childhood tuberculosis follows that in infants with undemutrition. A malnourished patient who
adults. While the global burden of the illness is unclear, it does not respond to dietary therapy should be investigated
is estimated that -10% cases occur in childhood. for tuberculosis.
Tuberculosis infection and disease among children are Children with primary or secondary immune
much more prevalent in developing countries, where deficiencies develop disseminated disease. Illnesses that
resources for control are scarce. It is estimated that in affect cell-mediated immunity (including measles)
developing countries, the annual risk of tuberculosis increase the susceptibility of disease. The risk of infection
infection in children is 2-5%. The estimated lifetime risk is associated with the extent of contact and burden of
of developing tuberculosis for a young child infected with organisms in the sputum. Patients with smear positive
M. tuberculosis, as indicated by positive tuberculin test, is pulmonary tuberculosis are more likely to transmit
about 10%. About 5% of those infected are likely to infection. An increased risk of infection is seen in
develop disease in the first year after infection and the institutional settings (nursing homes, correctional centers
remaining 5% later. These rates increase about sixfold in and homeless shelters).
HIV-infected individuals.
Reasons for an increase in childhood tuberculosis include Pathology
inadequate facilities for diagnosis, prevention and therapy, The inhaled tubercle bacilli lodge in pulmonary alveoli
the HIV pandemic, and emergence of drug resistance with and cause inflammation with hyperemia and congestion.
nearly 170000 children dying every year. Due to improved Initially, polymorphonuclear leukocytes infiltrate the site,
standard of living, the incidence of tuberculosis has declined but their phagocytic ability is low and they are soon
in affluent and highly developed countries. However, it eliminated. The further course depends on the immune
continues to be a public health problem in underprivileged response of the host. If host resistan~e is good, t~e
countries of Asia, Africa and South America. inflammatory exudate around the primary focus 1s
- 244
---
Essentlal Podiatries
absorbed nnd t·hc cnseous nrcn inspissatcd. Healing occurs unrecognized. Asymptomatic infection is defined
by fibrosis.nnd calcificntion. When the cell-mediated immune lnfection associate~ with tub~rculin ~y~e~sensitivity a~
7esponse is weak, the bncilli continue to multiply and the a positive tuberculin test, without significant clinical or
inflammatory process ext·cnds to the contiguous areas. radiological findings.
Progressive primary disease is a serious complication Symptoms in children with PPC include mild fever
of th~ pulmonary pr~mnry complex (PPC) in which the anorexia and weight loss; occasionally PPC are detected
PPC, mstead of resolving/ calcifying, enlarges steadily and during evaluation of intercurrent infection. Cough is
develops a ~arge cnse?us center. The center liquefies and inconsistent and may be absent even in advanced disease.
may e1~pty mt? an adjacent bronchus leading to formation Irritating dry cough can be a symptom of bronchial and
of a cavity, wluch charact~r~stically is associated with large
tracheal compression due to enlarged lymph nodes.
numbers of tubercle bac1lh. Next, the bacilli may spread
Lymph nodes may continue to enlarge even after
to other part~ of ~he lobe or the entire lung, resulting in
resolution of parench ymal infiltrates, and lead to
l~bar c~nsohdnt1on or bronchopneumonia. Cavitary
compression of neighboring bronchi.
disease is uncommon in young children. The enlarged
lymph nodes may co.mpress the neighboring airway. Ball- Progressive primary disease (PPD) is the result of the
valve .effect d~e to. mcomplete obstruction may lead to progression of primary disease. Children with PPD
trapping of air distal to obstruction (emphysema). present with high-grade fever and cough. Expectoration
Enl~rged pa.ratracheal nodes may cause stridor and of sputum and hemoptysis are associated with advanced
respiratory distress, and subcarinal nodes impinge on the d isease and development of cavity or ulceration of
esophagus and cause dysphagia. If obstruction of the bronchi. Cavitating pulmonary tuberculosis is uncommon
bronchus is complete, atelectasis may occur. in childhood. Children with endobronchial tuberculosis
usually present with fever, troublesome cough (with or
Outcome of Bronchial Obstruction without expectoration). Dyspnea, wheezing and cyanosis
i. Complete expansion and resolution of chest X-ray may be present. Partial compression of the airway can lead
findings to emphysema; features of collapse are seen with large
ii. Disappearance of the segmental lesions airway compression.
iii. Scarring and progressive compression of the lobe or Miliary tuberculosis, characterized by hematogenous
segment leading to bronchiectasis spread and multiple systemic foci, is common in infants
A caseated lymph node may erode through the wall of and young children. The onset of illness is sudden and
the bronchus, lea ding to tuberculous bronchitis or clinical features depend on the number of disseminated
endobronchial tuberculosis. Fibrosis and bronchiectatic organisms and involved organs. Unlike other forms of
changes may supervene. Discharge of bacteria into the tuberculosis, the child shows high-grade fever; dyspnea,
lumen may lead to their bronchial dissemination. cyanosis and altered sensorium are associated. There are
Hematogenous dissemination from infected lymph hardly any pulmonary findings, but fine crepitations and
nodes occurs early in course, resulting in foci of infection rhonchi may be present. Patients often show lymphadeno-
in various organs (e.g. Simon focus in apex of the lungs). pathy and hepatosplenomegaly. Choroid tubercles may
If the host immunity is good, these foci are contained and be seen in - 50% and meningitis in 20-30%.
disease does not occur. Lowered host immunity, as in Ple~ral effusion follows the rupture of a subpleural
infants, severely malnourished children and immuno- focus mto pleural cavity, but may also occur following
deficiency, may lead to activation of these metastatic foci hem~togenous spread from the primary focu s. The
and occurrence of disease. Massive hematogenous seeding effus10n occurs because of hypersensitivity to tubercular
with M. tuberculosis, usually within 3-6 months after initial proteins. Minor effusions are usually asymptomatic.
infection, leads to miliary tuberculosis where all lesions Tuberculous effusion is uncommon in children younger
are of similar size. than 5 years of age, and is rarely associated with segmental
Pulmonary tuberculosis resulting from endogenous lesion and miliary tuberculosis. The onset may be
reactivation of foci of infection is uncommon in children; insidious or acute with fever, cough, dyspnea, pain and a
but may be seen in adolescents. The commonest site for pleural rub. Increase in effusion may make breathing
this type of disease is the apex of the lung (Puhl lesion), shallow and difficult. Early signs include decreased chest
because blood flow is sluggish at apex. Regional lymph wall movement, impaired percussion note and reduced
nodes are usually not involved. Miliary and meningeal air entry on affected side. As fluid collection increases,
tuberculosis usually occur within 1 year of the primary signs of pleural effusion are more definite.
lesion.
Extrathoraclc Tuberculosis
Clinical Features The most common forms of extrathoracic disease in
The incubation period varies between 4 and 8 weeks. The children include tuberculosis of the superficial lymph
onset of symptoms is insidious, but may be acute in miliary nodes (scrofula) and the central nervous system. other
tuberculosis. Primary infection usually passes off rare forms of extra thoracic disease include osteoarticular,
Infections and Infestations I 24s -
abdominal, gastrointestinal, genitourinary, cutaneous and and history of contact with adult patients. Clinical features
congenital disease. may be nonspecific and chest radiograph and tuberculin
Tuberculosis of superficial lymph nodes may be test are difficult to interpret. In addition, these do not give
associated with drinking unpasteurized cow milk or conclusive evidence for the disease. While demonstration
extension of primary lesions of upper lung or abdomen of mycobacterium in various clinical specimens is the gold
leading to involvement of the supraclavicular, anterior standard, this is often not possible in children due to the
cervical, tonsillar and submandibular nodes. Although paucibacillary nature of the illness.
lymph nodes may become fixed to surrounding tissues, Histon1 of contact: A contact is defined as a child who
low grade fever may be the only systemic symptom. A lives in a household with an adult taking antitubercular
primary focus is visible radiologically in 30 to 70% therapy or having taken such therapy in the past 2 years.
patients; tuberculin test is usually reactive. Although A history of contact is available in less than one-third of
spontaneous resolution may occur, untreated lympha- the patients. Contacts can often be traced to a maid servant,
denitis frequently progresses to caseating necrosis, cook, domestic aid or gardener in case of patients from
capsular rupture, and spread to adjacent nodes and well-to-do families with healthy parents. Tracing of
overlying skin, resulting in a draining sinus tract. contact is useful for confirming the diagnosis, as well as
Central nervous system disease is the most serious protection of other susceptible children from the disease.
complication of tuberculosis and arises from formation of
a caseous lesion in the cerebral cortex or meninges, due to Laboratory Tests
occult lyrnphohematogenous spread. Infants and young Diagnostic tests for pulmonary tuberculosis can be divided
children are likely to experience rapid progression to into 2 categories based on demonstration of: (i) M.
hydrocephalus, seizures and raised intracranial pressure. tuberculosis or one of its components; (ii) host response to
In older children, signs and symptoms progress over M. tuberculosis.
several weeks, beginning with fever, headache, irritability Tubercle bacteria can be demonstrated by (i) Ziehl-
and drowsiness. The disease advances with lethargy, Neelsen (acid-fast) staining, (ii) special stains, (iii) cultures,
vomiting, nuchal rigidity, seizures, hypertonia and focal and (iv) cartridge-based nucleic acid amplification test.
signs. The final stage of disease is marked by coma, The above methods can be used on sputum, induced
hypertension, decerebrate and decortica~e postur~g.and sputum, gastric or bronchoscopic lavage fluid, or pleural
death. Rapid confirmation of the diagnosis can be d~f1~ult fluid. The best specimen for demonstration of M.
because of variable cerebrospinal characteristics, tuberculosis in children is the early morning gastric aspirate
nonreactive tuberculin tests (40%) and normal chest obtained by using a nasogastric tube. For better results, at
radiographs (50%). Since better outc01:nes ar~ associated least two specimens of gastric aspirates are recommended.
with early institution of therap~, the di~gnos1s sh_oul? ?e Fluorescence microscopy (using auramine-rhodamine
considered in any child with basilar memng1hs, stains) may improve yield further. In young children who
hydrocephalus or cranial nerve involvement. are not able to provide sputum, that can be induced ·by
Tuberculosis of abdomen is due to hematogenous nebulized hypertonic saline (3-5%). Older children may
spread from the lungs. It may, however, be sec~ndary_ to provide expectoration at end of the procedure. In young
swallowing of the infected sputum b~ a patient w1t_h children, a nasopharyngeal aspirate is collected and
ulmon lesions. Patients with abdorrunal tubercu.los1s processed like sputum for smear and culture.
p ary
may remain asymptomatic · rm
· ·ti· a llY· Symptomatic
. . patients
.. Culture: Lowenstein-Jensen (LJ) medium is the most
show toxemia and have colicky abdominal pain, v?~tmg widely used medium for determination of charac.teristic
and constipation. The abdomei:1 ~eels characteristically features of colonial morphology, growth rate and pigment
doughy· abdominal wall is not ngid but tense. The rolled production. Though the culture technique is simpl~, 7-10
up om~ntum and enlarged lyi:'ph _nodes appear as weeks of incubation is necessary for detect10n of
irregular nodular masses with ascites; liver and spleen are organisms. Microscopic examination of thin lay.er culture
often enlarged. h tic plate may lead to detection of microcolomes of M.
Children may rarely present with hemop. agocy. tuberculosis as early as after 7 days. T~e ~ield ?f culture_of
. (HLH) immune hemolytic anemia,
1ymphohistiocytos1s gastric aspirate varies from 30-50 Yo m ch1ldre~1 with
' th · ax and
. d. . 1 drome pneumo or tuberculosis. In view of the excessivelr_ long period for
superior me iastma syn ' d (005) in
immune reconstitution infl~atory syn :~:r startin isolation of M. tuberculosis by convent10nal. culture, LJ
form of paradoxical worserung of symptom .th . un! media has been replaced by my~obactenal growt_h
antituberculous drugs, especially in children Wl unm indicator tube (MGIT) system. In this system, .culture~s
deficiency. positive in majority by end of 2 weeks, though final res t
is available by the end of 6 weeks.
Diagnosis
. . h'ldren is based on Cartridge-based nucleic acid amplification te~t (CBN~T!:
The diagnosis of tuberculosis m c 1 ulin t tin The test, based on real-time polymerase chain reaction, is
clinical features, chest roentgenogram, tuberc es g
- -246 Essontlal Podiatries
preferred for dlngnm1ls of pulmonary tuberculosis; results [ ·Table 11.6: Causes of false positive and false negative
ore nvailnblc In less thnn 2 hours. CONAAT identifies I tuberculin skin test (Mantoux test)
presence of M. l111'erculm1is nnd providcR information on . False negative results False positive results
rlfompicln rcsistnnce. 'l11c sensitivity and specificity of two Infections Infections due to atypicaJ
gnstrk nspiralcs for dingnosing pulmonary tuberculosis in Vlral (measles, mumps, chickenpox, mycobacteria
children rnngcs between 60-70rYo and 90-100%, respectively. HIV) BCG vaccination
ltR utility in extrnpulmonary tuberculosis is lower. Bacterial (enteric fever, typhus, leprosy, Infection at the site of
Serotllaguos/s: EUSA has been used to detect antibodies pertussis, severe TB) test
to vnrious antigens of the bacillus. Despite a number of Live vaccines (measles, mumps, polio,
studies, current l'echniques have no role for the diagnosis varlcella)
of tuberculosis in children. Chronic renal failure, liver failure
Hodgkin disease, lymphoma, chronic
MeN10tl~ to tlfrlg11ose latent- infection: Till date, tuberculin
leukemia, sarcoidosis
skin test was the only method to diagnose latent
Corticosteroids, immunosuppressive
tuberculosis infection. Recently, a new test based on
agents
interferon gamma release assay (JGRA) has been developed.
Newborn, elderly patients
This in vitro test estimates n component of cell-mediated
immunity to M. tuberculosis, based on quantitation of Factors related to tuberculln
intcrfcron-gnmmn (IPN-y) released from sensitized Exposure to light, heat, chemicals;
lymphocytes in whole blood incubated overnight with contamination
antigens specific for the bacterial species. Two tests are Improper dilution; adsorption
nvnilable: QuantiFERONifJgold TB test (QFT) and ELISPOT. Factors related to technique
In countries with high prevalence of tuberculosis, it is Injection of too little antigen
recommended to continue using tuberculin skin test that is Subcutaneous injection
considerably Jess expensive than IGRA. Delayed administration after drawing
into syringe
T11lJerc1tlin skin lest-: The tuberculin or Mantoux test is
Injection close to other skin tests
commonly used to make the diagnosis of tuberculosis in
Inexperienced reader; errors in recording
children. Although currently available test antigens are
not 100% sensitive or specific, no better diagnostic test is test is based on risk of infection and progression to disease
widely available. Infection with M. tuberculosis produces (Table 11.7).
a delayed hypersensitivity reaction to its specific antigenic
components. All purified protein derivative (PPD) lots are BCG test: An accelerated response after injection of the
bioassayed to demonstrate equal potency. The standard vaccine is observed in individuals suffering from
test dose of a preparation is defined as dose of that product tuberculosis. Induration of more than 5-6 mm after 3 days
that is biologically equivalent to 5 TU of PPD-5 or 2 TU of of BCG vaccine is considered a positive reaction. However,
tuberculin PPD RT23. The reaction to tuberculin typically due to high antigen load, there are higher chances of false
begins 5-6 hours after the intradermal injection and positive results and this test is not recommended.
reaches maximal induration at 48-72 hours; vesiculation
and necrosis are rare. Radiology: Chest radiograph has an important role in
Variability of the tuberculin test may be reduced by diagnosis of pulmonary tuberculosis. In extrapulmonary
attention to administration and reading. A 26-gauge tuberculosis, presence of lesions on chest radiograph
needle and tuberculin syringe are used to inject 0.1 mL of supports diagnosis. The typical chest X-ray appearance
PPD intradermally into the volar aspect of the forearm. of a pulmonary primary complex (PPC) is that of a
consolidation of variable size, usually unifocal and
Forty-eight to 72 hours later, the diameter of induration
homogenous (Fig. 11.15). Enlarged lymph nodes are seen
is measured transversely to the long axis of forearm and
in the hila and right paratracheal region. Adenopathy
recorded in millimeters. A non-reactive tuberculin test
does not exclude latent or active tuberculosis. Numerous .- ··--· -Tabi~-11.1: '1nterp~etation oi Mantoux te~t
factors can diminish tuberculin reactivity, resulting in a
Size of induration Interpretation
false negative reaction (Table 11.6). Because some antigens
in PPD are shared with other mycobacteria and Bacillus <10 mm Negative; no active disease
Calmette-Guerin (BCG}, false-positive reactions can occur 5-10 mm Borderline; consider positive in immuno·
in those infected with other mycobacteria or following compromised host; contact with adult
vaccination. Although BCG vaccination of older children patient with sputum AFB positive tuber·
culosis
or adults results in greater initial and more persistent
cross-reactivity, most individuals lose cross-reactivity >10mm Positive; suggests disease in presence
within 10 years of vaccination. Interpretation of the skin of clinical features
Infections and Infestations I 241 •
alone may be the sole feature of primary tuberculosis. detected on computed tomography. CT features such as
Consolidation in progressive primary disease (PPD) is low attenuation lymph nodes with peripheral enhance-
usually heterogeneous, with poorly marginated predilec- ment, lymph node calcification, branching centrilobular
tion for apical or posterior segments of upper lobe or nodules and miliary nodules are helpful in suggesting the
superior segment of lower lobe (Fig. 11.16). There may be diagnosis where the radiograph is normal or equivocal.
features of collapse (Fig. 11.17). Bronchiectasis may occur Contrast MRI is useful for CNS tuberculosis, since it
because of (i) destruction and fibrosis of lung parenchyma demonstrates localized lesions, meningeal enhancement,
resulting in retraction and irreversible bronchial dilatation, brainstem lesions and ventricular dilatation.
and (ii) cicatricial bronchostenosis secondary to localized
endobronchial infection resulting in obstructive pneumo- Histopatlwlogtp Lymph nodes, liver and other tissues
nitis and distal bronchiectasis. In children, cavitary disease may be examined for histological evidence of tuberculosis
is uncommon. by fine needle aspiration cytology.
Pleural effusion may occur with or without lung lesions
(Fig. 11.18). In miliary tuberculosis, there are multiple Diagnostic Algorithm for Tuberculosis
lesions of size 2-5 mm (Fig. 11.19). Occasionally, the chest The diagnosis of tuberculosis disease in children is
radiograph may be normal and lyrnphadenopathy is challenging. Even in advanced nations, the diagnosis is
-1
Fig. 11.15: Pulmonary primary complex (PPC] showing left hllar Fig. 11.16: Progressive pulmonary d isease showing consoli-
adenopathy with ill-defined parenchymal lesion dation
Fig. 11.17: Collapse with consolidation of right upper lobe Ag. 11 .18: Massive ple\Jral effuslon on left side, with medlastinal shift
11 24e
Drug Reg/mens .
ave occurred in the therapeutic approach 1
Qan~ h h o
childhood tuberculosis. Short cour.se t erapy, With
treatmen t du ration of 6 months, is now standa rd
practice. . . . .
The major problem in mclus1on of children m Directly
Observed Treatment Short ~ourse (DOTS) progr~ ~been
a difficulty in demonstration o~ AFB and cl3:'sification of
different manifestations according to cate.gones described
for adults. A joint statemen~ of the Indian A~ademy of
Pediatrics and Revised National Tuber.culos~s Control
Program (RNTCP) has proposed. to classify childre.n into
two categories. Table 11.9 gives the c~tegones of
tuberculosis, as defined by WHO, along with suggested
clinical condition in children. In view of increasing INH
resistance, use of three drugs (INH, rifampicin and
ethambutol) instead of two (INH and rifampicin) is
Fig. 11.19: Mlllary shadows with right paratracheal adenopathy suggested during the continuation phase.
Suspected pulmonary TB
• Fever and/or cough >2 weeks
• ± Loss of weight or no weight gain
• History of contact with suspected or diagnosed active TB
Look for alternative cause for symptoms
+
•
X-ray not suggestive of TB
Antibiotics for 7-10 days, if has not already received
Symptoms persist
Gastric aspirate (GA), Induced sputum: Smear, geneXpert, MGIT
+
Gastric aspirate, induced sputum:
Smear, MGIT, geneXpert
Sputum or GA positive Negative or not feasible
! +
Symptoms persist
Sputum positive Sputum negative
Assign to a category Repeat chest X-ray
and treat after 2-4 weeks
Assign to a category and treat
+
X-ray after 2-4 weeks
Chest X-ray suggestive of TB
Positive tuberculin test, documented contact
Tuberculin positive and Investigate for TB,
abnormal X-ray other diagnosis
.'_ . . - ~able 11.~: Standardized .clinical categories for tuberculosis (TB)-and cli~ical con-ditions -
, Categories Suggested by WHO Suggested conditions (for adults) Suggested regimens' in children
Category I New sputum positive PPC, PPD, TBL 2HRZE + 4HRE
Pulmonary TB Pleural effusion
Serious extrapulmonary TB Abdominal TB
Osteoarticular TB
Genitourinary TB
Central nervous system TB
Pericardia! TB
Category II Relapse Relapse 2SHRZE + 1HRZE + 5HRE
Treatment failure Treatment failure
Return after default Interrupted treatment
PPC: Pulmonary primary complex; PPD: Progressive primary disease; TB: Tuberculosis; TBL: Tubercular lymphadenitis
H isonizid, R rifampicin, Z pyrizinamide, E ethambutol, S streptomycin
'Numerical denotes months for which the drug is to be given; e.g. 4HR is 4 months of INH and rifamplcin
All children in household of an adult patient with sputum positive tuberculosis should be screened for evidence of infection. Children exposed to
adults with sputum positive illness should receive 6 months of isoniazid prophylaxis.
In presence of unsatisfactory response or worsening of • Jenum s, Dhanasekaran s,. Lo~a R, et al. ~pproaching a diagnOstic
features, the initial basis of diagnosis is reviewed point-of-care test for pediatric tuberculosJS through evaluation of
immune biomarkers across the clinical disease spectrum. Sci Rep
especially if there are no issues with compliance. Th~
2016; 6:18520.
possibility of drug resistant tuberculosis should be • Lodha R, Mukherjee A, Saini D, e.t al; Delhi TB. Study ~roup. Role
considered. Following completion of therapy, patients are of the QuantiFERON®-TB Gold m,-Tube test rn the diagnosis of
reviewed every 3-6 months for 2 years. intrathoracic childhood tuberculosis. Int J Tuberc Lung Dis 20IJ;
11:1383-8 .
Radlologlcal Criteria • Mukherjee A, Singh S, Lodha R, et al; Delh~ Pediatric TB Study
Clinical improvement precedes radiological clearance. The Group. Ambulatory gastric lavages provide better yields of
Mycobacterium tuberculosis tha~ induced s~utum in children With
first chest X-ray is done after 8 weeks' therapy, i.e. at the intrathoracic tuberculosis. Ped1atr Infect Dis] 2013; 32:1313-7.
end of intensive phase. In patients who show increase or
• Seth V, Kabra SK (Eds). Essentials of tuberculosis in children, 3rd
little change in radiological features coupled with delayed edn. New Delhi, Jaypee Publishers; 2010.
clinical response, prolongation of intensive phase by one-
month is suggested. Further films are taken after 4 weeks Mycobacterla Other than Tuberculosis (MOTI')
and child, if better, should be shifted to continuation
phase; else the patient is investigated for failure of Atypical mycobacteria or non-tuberculous mycobacteria
treatment and drug resistance. The degree of radiological (NTM) or mycobacteria other than tuberculosis (MOT!)
clearance is graded as: (i) complete, (ii) moderate o~ ~rd - are environmental pathogens that are being increasingly
recognized as cause of human disease. These bacteria are
clearance), (iii) mild (~rd decrease in size), or (iv) no
clearance or appearance of new lesion(s). One need not classified depending on the rapidity of growth in media
treat till complete radiological clearance, since improve- as rapid growers which grow within 7 days and slow
ment may continue even after stoppage of therapy. growers, as those which take longer to grow. Acquisition
is through contact with the environment; human-to-
Mlcroblologlcal Criteria human or animal-to-human transmission almost never
Childhood tuberculosis is paucibacillary. In children, occurs. Though asymptomatic infection can occur, there
where isolation of M. tuberculosis was possible at the time is no recognized latent infection or reactivation disease.
of diagnosis, efforts are made to document disappearance NTM infections may occur in previously healthy or those
of bacilli during therapy. If smear was positive initially, with underlying immunodeficiency, like HIV.
repeat sampling is done at 2 and 6 months. Lymphatic disease is the most common manifestation
Suspecting Drug-Resistant Tuberculosis of NTM disease in children. It usually presents as painless
cervical adenitis in children aged 1-5 years with no
Children in the following categories are at risk of develop- systemic symptoms. The main differential is tuberculous
ing drug resistant tuberculosis: Contact with adult patients lymphadenitis. The definitive diagnosis is by culture; the
with proven drug resistance; irregular treatment or recent ~sual causative organisms are MAC (Mycobacterium arium
~licrobiologic dlngnosis of NTM lnfecthms ls po~slblc In lndin. Cnscs have lw1.•n reported from all states chiefly
ii\ ~ped <llizcd lnb()rntories wh1.n·c identificntlnn nnd from rum! nnd forested nrcns and occnsionnlly also urban
Sl l'\':iatll'll is done by nd\'nnct.•d b\~)chcmknl ot• moll-culnr nrcns.
1ncthods. l't-c ltment depends on tlw cirn~ntlve nrAnnism Scrub typhus is trnnsmittcd by bite of the trombiculid
{Ind it:' St.'nsiti\'ity. !vtAC ig usunlly trt.\lh'd with cnmbinn· mile and lndinn spoll'cd fever by ticks. Rickettsial disease
tion tht.'l'llpy rnnsisting of n mncrolide (dnrilhrnmycin/ is due to invn s ion of the endothelial region of the
:l7.ithromycin), rifompicin, cthnmbutol nnd during initial vnsculnturc nnd subsequent microvasculitis. This process
shl~t.'S with nn nminoglycosidc for 12-'18 months. espcdnlly nffccts the brnin, cnrdiac and skeletal muscle,
Trl'Lltmcnt of the rapidly growing mycobnctcrin (1\tl. skin, liver, lungs nnd kidneys.
11l~n~'ll~.1\ f. d1do1111t•, lvl.fort11it11111) includes n combinntiun
of clnrithrornycin, quinoloncs, nminoglycosides, Cllnlco/ Monlfestollons
tobrnmycin, amikadn, imipenem, minocyclinc, linezolid Incubation period varies from 2 to 1-l days. A history of
and dofozimine. exposure to ticks, history of origin from an endemic area
or a similar illness in family members may be forthcoming.
Suggested Reading
Severity of mnnifcstations varies from a mild, self-limiting
• ATS/ lDSA Stntcmcnt: Dingnosis, trcntnwnt nnd prcn~ntion of illness to a life-threatening disease.
m'ntulicn:uk•us mycobncterinl disenses. Am J Rcspir Crit Cnn.! Ivied
2007; li5:367-416. Initially, the illness appears to be nonspecific and patients
• BTS Guidt'lines for the mnnngement of non-tuberculous present with unrelenting headache, very high fever,
mycobucterinl pulmonary disense. Thornx 2017; 72:969-10. anorexia, myalgias, restlessness, calf muscle pain and
tenderness. Gastrointestinal symptoms include abdominal
RICKEITSIAL AND MYCOPLASMA INFECTIONS pain, nausea, vomiting, and diarrhea. Skin rash is usually
not present until after 2-4 days of illness. The typical triad
Rlckettslal Infections
of fever, headache and rash is observed in only half of the
Rickettsial diseases are a group of febrile illnesses caused patients. In spotted fever, rash is initially discrete pale rose
by obligate intracellular gram-negative bacilli and red blanching macules or maculopapules on the extremities.
transmitted to man by arthropod vectors. Rickettsial Later, the rash spreads to involve the entire body including
diseases are often under diagnosed due to poor awareness. palms and soles and may be petechial or present as palpable
purpura (Fig. 11.21). In severe form of the disease, petechiae
Epidemiology may enlarge into ecchymosis, which can become necrotic.
Rickettsia are a group of motile, gram-negative, nonspore· Severe vaso-occlusive disease secondary to rickettsial
forming, highly pleomorphic bacteria that present as cocci, vasculitis and thrombosis is infrequent but can result in
rods or thread-like obligate, intracellular parasites. gangrene of the digits, toes, earlobes, scrotum, nose or entire
Rickettsia are classified on basis of clinical features and limbs (Fig. 11.21). In scrub typhus, rash is seen initially on
epidemiology into the typhus group (epidemic typhus, trunk or may not be present at all. Painless eschar, tile tache
endemic typhus and scrub typhus), the spotted fever noire, at the initial site of tick attachment is seen in scmb
group (Rocky mountain spotted fever, Indian spotted typhus.
fever), Q fever, trench fever and ehrlichiosis. Scrub typhus Complications may involve any organ system and
caused by R. tsutsugnnmsl1i, Indian spotted fever caused include encephalopathy, pulmonary edema, myocarditis,
by R. conorii and Q fever caused by C. burnetii are prevalent hepatic failure, acute renal failure and vascular collapse.
- 252
FUNGAL INFECTIONS
Fungi have become an increasingly common cause of
disease in humans. Superficial fungal infections are
occurs in the immunocompromised; common pre-
disposing factors include patients with cancer undergoing
chemotherapy and resultant neutropenia, stem cell
transplant recipients and patients on other immuno-
suppressive drugs. Common sites of involvement are the
I
detailed in Chapter 26. We discuss some of the serious lungs (Fig. 11.22) and sinuses. Clinical symptoms and signs
invasive fungal infections, including invasive candidiasis, depend on the site of involvement. Diagnosis is primarily
aspergillosis, mucormycosis and cryptococcosis. by radiology and histopathologic demonstration of the
invasive hyphae in biopsy samples and finally by culture.
Invasive Candidlasis Estimation of galactomannan in serum/bronchoalveolar
The major infection causing species of Candida are lavage samples has emerged as a non-invasive diagnostic
C. albicans, C. tropicalis, C. parapsilosis, C. krusei and test. Treatment should be aggressive. The drug of choice
C. glabrata. It commonly causes superficial infections such is voriconazole. Other options are amphotericin Band caspo-
as thrush, vaginitis, paronychia, etc. Colonization with fungin. Fluconazole has no activity against Aspergillus.
Candida at mucosal sites in patients on antibiotic therapy Surgical resection may be required in non-responding cases.
is also common. Invasive infections with Candida usually
happen as nosocomial infections in individuals with Mucormycosls
impaired defenses such as preterm neonates in the Mucormycosis refers to infection with the filamented fungi
neonatal intensive care unit, critically sick children in of the genus Mucor and Rhizopus. The hyphae are broad
the pediatric intensive care unit and children with cancer and aseptate unlike those of Aspergillus that are narrow
on chemotherapy or following stem cell transplant. The and septate. Mucormycosis is an invasive infection that
Usual risk factors for invasive candidiasis include primarily occurs in patients with risk factors such as
prolonged intensive stay, broad-spectrum antibiotic diabetic ketoacidosis, cancer chemotherapy, transplant
~herapy, renal failure, corticosteroid and other recipients, iron overload and receipt of immuno-
lllUnunosuppressive therapy, renal failure, use of total suppressive drugs. Sites of involvement are mainly the
-
- 254
PROTOZOAL INFECTIONS
Mal aria
Malaria the most important protowal dLwa~ of man i~
caused by the genus Plasmodium. There are four Bped~'1
pathogenic to man, P. vivax, P. falcip~rum, ~'· malariae arid
P. ovate of which the first two occur in J~d1a. Moot of thP.
malaria deaths are attributable to P. falc1parum.
Epldemiolog;
Malaria is an important tropical disease, afflicting
350- 500 million patients annually with aver one miJlfrm
deaths. Of regions endemic for malaria, >70% cases are in
Sub-Saharan Africa. Malaria is also an important cause of
morbidity and mortality in South Asia including India.
Fig. 11.22: Multiple air space opacities with irregular borders The National Vector-Borne Disease Control Program
and internal cavitation suggestive of invasive aspergillosis reported around 0.8 million cases of malari.a in India in
2014 with some 300 deaths; 60% of the cases were due to
nasal sinuses and less commonly pulmonary, gastro- P. faciparum. Large number of cases are report~d from
intestinal and skin/ soft tissue. Infection can sometimes Orissa, Chhattisgarh, West BengaJ, Kamataka, ]hz.r1'-J1Z.nd,
occur due to direct inoculation in traumatic/surgical Madhya Pradesh, Uttar Pradesh, Assam, Gujarat a.n.d
wounds and injection sites. Clinical features depend on Rajasthan. About 10% cases are reported from the urban
the site involved; in the nasal form pain, swelling, bloody areas, due to construction activities, population migration,
discharge and presence of blackish eschars on nasal and inappropriate water storage and disposal
examination are common. Confirmation of diagnosis is by
demonstration of the characteristic hyphae on histopatho- Transmission
logy and ftmgal cultures. Treatment includes radical surgical The infectious stage of the parasite, the sporozoit:, i5
debridement, antifungal therapy with amphotericin Band transmitted to the host by the bite of the female Ancpf:~!~
correction of underlying predisposing factors. mosquito. Six species of anopheline mosquitoes ~re
important in the transmission of the disease, na=.:ly
Cryptococcosls
Anoplzeles culicifacies (rural), A. jluvitalis, A. stepf:!.._Ei
Infection with Cryptococcus r1eofon11a11s is commonly seen (urban), A. minimus, A. philippinesis and A. sur..daiD.1:.. To
in HIV-infected individuals with advanced immuno- enable de..-elopment of parasites in the vector's bodY ::nd
suppression and less commonly in other immuno- make it capable of transmitting the disease, the :;:::st ,·ecto;
compromised patients such as those on long-term be susceptible, feed on human blood and J.i.-e at ]east '.or
steroids, or those with CD-! lymphocytopenia. Rarely, it 10-12 days after an infecti\·e blood meal Tne vector s!lc;-.i1d
may occur in the irrununocompetent (usually due to C. be present in large number or sufficient densitv to b: of
gattii). The disease most often affects the central nerYous importance. Resting habits of the mosquito are ~po:-t<...'11
system; pulmonary and disseminated forms are less for planning control measures. }.fosquitoes usu.all..- br:~
common. Clinical symptoms include headache, Yomiting, in edges of streams, water tanks, pits, cisterns and o·:c:r·
altered sensorium, signs of meningis m and less head tanks. A. stephen.si breed in wells, cisterns, foun \:d.S
commonly neurologic deficits. CSF is usu ally under and o~erh~d tanks •. A fluviatili.s in moving ,.;ater and .A..
increased pressure and has high protein \\ith pleocytosis. su11da1cus 1:1 brackish water. Breeding sites such as
The diagnosis is confirmed by demonstrating cryptococci burrowed pits, pools, ponds, ma..-shy areas and unreguk~
in the CSF by India ink, cryptococcal antigen testing and irrigation channels are conduciye to mosquito breeding
finally culture. Treatment includes antifungal therapy a nd spread of malaria. ~fosquitoes thriv e best ]Jl
with amphotericin Band flucytosine for 2 weeks followed temperature between 20 and 3(}0 C, relatfre humidity 60%
by fluconazole for prolonged periods. Reduction of and in areas with good rainfall The peak tran.smisSio!l
elevated pressure by serial lumbar punctures is also season of malaria is benveen July and Nm-ember. ~fa]zP..a
crucial. is uncommon at altitudes over 2{X)() m above sea le\-el
Infections and Infestations 1255 -
Efficient vectors are those that bite humans in
preference to cattle, have high biting rates and where the
duration of sporogony is shorter and who are long lived
(hence they outlive sporogony). More efficient the vector,
greater the b:Ud~n of malaria; A. gambiae the vector in Sub-
sahara~ Afnca is a very efficient vector and is largely
responsible for the huge burden of malaria in that area.
Life Cycle of Parasite
Humans
Hepatic o~ t~s~ue phase: When an infectious mosquito bites
a human, it Injects sporozoites, which circulate and invade ' ...
hepatocytes and reticuloendothelial tissues within ·~
30 minutes of the bite. During hepatic infection, P. vivax
produces 2000-15000 merozoites and P. Jalciparum
produces 40000 merozoites by repeated divisions. These
merozoites are released and invade erythrocytes at end
of the hepatic phase. The first hepatic phase is
asymptomatic and constitutes the incubation period. This
cycle lasts at least 10 days (1-2 weeks for falciparum
infection).
Fig. 11 .23: Gametocyte of P. falclparum
Erythrocytic phase: After replication in the liver
in the liver and cause relapses by invading the
(exoerythrocytic schizogony), the parasites undergo bloodstream weeks or even years later. This intermittent
asexual multiplication in the erythrocytes (erythrocytic release of schizonts in case of P. vivax and P. ovate may
schizogony). In erythrocytes, parasites develop into ring last for 2-3 years and for P. malariae for 10-20 years.
forms, mature trophozoites and then multinucleated
schizonts, which rupture and release more merozoites. Mosquito: The gametocytes are ingested by an Anopheles
Repeated cycles of erythrocyte invasion and rupture lead mosquito during a blood meal. The gametocyte forms
to chills, fever, headache, fatigue, and signs of organ survive in the stomach of the mosquito; all other stages
dysfunction. are destroyed. The parasites' multiplication in the
A key feature of the life cycle of P. Jalciparum is mosquito is known as the sporogonic cycle. While in the
cytoadherence, whereby erythrocytes infected with mosquito stomach, fertilization of female gametes
mature parasites adhere to endothelial cells in the generates motile and elongated zygotes (ookinetes) that
microvasculature. This process is presumably invade the midgut wall and develop into oocysts (resting
advantageous to the parasite, since it prevents the passage stage). These oocy sts grow , rupture and release
of abnormal erythrocytes through the spleen. High sporozoites that reach the mosquito salivary glands.
concentrations of P. falciparum infected erythrocytes in the Inoculation of the sporozoites into a human host
microvasculature and a complex interplay of host and perpetuates the life cycle.
parasite factors lead to the manifestations of severe
malaria, including cerebral malaria, noncardiogenic Immunity Against Malaria
pulmonary edema and renal failure. Because of the ability Iti11ate a11d acquired resistance: Innate resistance in
of mature P. falcipantm organisms in the erythrocytic stage malaria may be due to differences in the surface receptor,
to adhere to endothelial cells, only ring forms circulate intraerythrocytic factors or yet unkno w n causes.
(except in very severe infections), and levels of peripheral Epidemiologic observations suggest that patients with
parasitemia may be low despite substantial infection. sickle cell trait, thalassemia and glucose-6-phosphate
dehydrogenase deficiency are relatively immune to
Gametocytic phase: After several stages of schizogo~y, malaria. Homozygotes of sickle cell disease are no t
some merozoites are converted to gametocytes (Fig. protected from malaria but heterozygotes are immune.
11.23) which are taken up by the mosquitoes. Th~y _do Variations in HLA frequency may also determine the
not cause symptoms but are responsible for transmission prevalence of malaria.
of malaria. Acquired immunity against malaria is both cell-
Exoerythrocytic phase: Termination of the ery~oc~tic mediated and humoral. The first response to malarial
5chizogony does not necessarily terminate the infection infection is phagocytosis in the spleen or the hyperplastic
With malaria because merozoites of P. vivax, but not those reticuloendothelial cells of the parasitized erythrocytes.
of P.falciparum, may go into a dormant stage (hypnozoite) IgM antibodies against the merozoites help in opsono-
- 256 I Essential Pediatrics
~-r--- ,
therapy. Additionally peripheral smears are cheap and l~ ·~.--..._._..:. - ..... . ·----~ I. P. vivax
readily available. The main drawback is need for expertise
and that they are time consuming (careful examination of
100 fields needs 20 minutes). Sometimes peripheral smears
may be negative due to partial antimalarial treatment or
~-' , .-~ I P. talciparum
I
empirical therapy. This is to prevent irrational therapy of action. Similarly, if an area has resistance to
and consequent drug resistance and also to avoid missing pyrimethamine sulfadoxine and mefloquine, then these
other causes of febrile illness. should not be used as part of combination therapy.
Vivax malaria: The drug of choice for managing vivax Artemisinin-based combination therapy (ACT) is the
malaria is chloroquine. Resistance to chloroquine has been treatment of choice for falciparum malaria (Table 11.9).
rarely reported in India. The total dose is 25 mg/kg; first Artemisinin (qinghaosu) is the antimalarial extract isolated
dose is 10 mg/kg, followed by 10 mg/kg after 24 hours from Artemisia annua. Artemisinin and its derivatives
and 5 mg/kg at 48 hours (Table 11.11). Fever should be (artemether, artesunate, arteether) are the most rapidly
r,:-:--· · --.- --· --- r "fab~e · 11.11: Drug _dose~ fororal_antin:~~fia( ~ugs......:--· -:·~ .--.~ ·.~ - .. ;~· .-~···. :]
' C.hlo~~q-ui~e -(tablets 250 mg salt.with 150 mg base; syrup Loading dose; 10 mg/kg of base; 10 mg/kg after 24 hours and
~o mg base/5 ml) then 5 mg/kg at' 48 hours
Prlmaquine (7.5/15 mg tablets) 0.25-0.75 mg/kg
·Artemether and lumefantrine (tablets having 20 mg artemether Weighing 5-14 kg, 15-24 kg, 25-34 kg and >34 kg Is 1, 2, 3
and 120 mg lumefantrine; syrup artemether 40 mg and 240 mg and 4 tablets, respectively. Administer 0, 8, 24, 36, 48 and 60
.1.umefantrlne per 5 ml) hours1 .7 mg/kg of artemether twice daily for 3 days
.Artemether (syrup 40 mg/5 ml) 4 mg/kg/day single dose
·Mefloquine (250 mg tablets) 25 mg/kg; two doses of 15 mg/kg and 1O mg/kg 8 hours apart
Pyrimethamlne sulfadoxlne 1.25 mg/kg of pyrimethamine single dose
'Doxycycllne 3.5 mg/kg/day
Cllndamycln 1O mg/kg/day twice daily
~uinlne (tablets contain 300 mg)
.. . . .
_ _,
- . . .. --
1O mg/kg thrice dally
- 258 E11ont1nl Pndlntrlc•
acting of all antimala1fals; they also h•Wl' wklc spcdn1t1\ I~ t\llmlnliJh.'t'l!d (.~,.,, r1h11w). 1\ til11Hlt! dnitu nf r"rl11111qu1 1111
antimalarial effect from ring forms to m1\h1t>c troph1)t.ollcs ..r:
0.1~ /1.ll .. hiHlhl Ii,! 11ttt1d ltl rcid11n l'lr•k of l1·r111ttinln111 1111
1
lllM "n o I I' 1 . '
(like chloroquine and unlike quinine lhot l\Cls only on i\rll.'ml~lnln llL1rl\'11llvw1hrt\lll11 KtHll n11 1 ly prnlll11, l.11i·~1
mature forms). Artemether lumefontrlm~ is llH~ nHJ1ll l'l'ill'. tllll\H rllh'l' lllll'1 \lllllllt:lll11l' nd111l11lt1l1'11ll0ll lll't1l'fll'l•11nd
commonly used oral ACT. Other drngs such (IS mdlo· 11\U(h lt•:iH fi·1•q111~ 11l 11:~ 1~ 1H11p<lt'od lo IM q11l111n 11 ,
quine, amodiaquine and pyrimdh;\minc-sulfodoxine m1w t\u·dloli1\k L'lft'l' l~11t1 tlw f11rnl ol' prol1111p.r1llo11 or llw Q'I'
be used in combination with i'lrtcstllli'lle in ;\l't'flS \\'her~ lntcr\'•ll ln l''1tl1•11b1 ''''l'l1 h•li1H high do111• 111·h·11wll11•r h11v1.1
resistance to these drngs is uncommon. 1\ rterolonc m;1kntc hl't~n nvi1rtl·il. t\rli•111hil11lrn1 11h1111ld 11111 lw rnmhltwd wllh
plus piperaquiJ1e phosphate is also an alfrclivc ACT. Orn I othet' (i\rdlulllxk dt'llKH ~n1d1 mi qul11l11e 1md l111luf111111'1no,
quinine with clindamydn or doxycycline (in children :>8- l'hysich111~ shlluld lw 1HV1ll'i~ 11houl r1 1porlH of 11u11roloxlc1ty,
year-old) for 7 days is a1' alternate treatment, but is cspl'l:ll1lly with l'L'pc1\ted w1c, 1rnd lltll'l't{llltllt'd llwrnpy.
associated with poor tolernbility of ornl quinine nnd 111.•ed
for prolonged therapy. Quit1i11c'·ltt1s1·1l llH•1·1111y: <J1.1l11lt1c 11dN pl'lnc:lprllly 011 lltu
Chloroquine should not be used for treatment for nrnlmc trnpho1.olll' Hlc1p,e tll p111·11.~ llo 1lt~wlop11wnl; It dot·~
fakiparum malaria unless there is denrnnstrnblc not prl•vcnt Hl'qucsl1'1\lhlll 11r l11rlhcr dev1•lop1111•11l uf
sensitivity to the medication; similarly mdloquine and formed mcrnnts nml doc1:1 nol klll llw prt!·t'l')1 ll11·01:ytlc or
pyrimcthamine sulfadoxine monothernpy is not scxunl stngc o( J>/11:m1odi11111 ji1ll'i1 1,11·11111. 1'1m•11t1•r11I q11i11l11(l
recommended. At the end of ontimnlnrial thet\\py, n is nv 1ll.1ble nH dlhydroi.:hln1·ldc Hnlt In l:1mn•11lrntlo111l C>(
single gametocidal dose of primoquine (0.75 mg/kg) is 300 mg/mL. Qulnl1w m111-1t 11lwnys bu glvL1 11 l>y l'11lu
recommended to reduce community trnnsmission of controlled inll'llVl'l\lllll'I lnfuslun 11ml ncvor by b11h111 or
malaria. push injection. It Is n•i.:ommcnd1•d lo 11dmlnl1-1te1· 11 lo11dlng
dose of quinine, i.e. 20 mg suit/kg dll11tcd In HI ml./k11 of
Urrcomplicated mixed rr111lari11: Uncomplicated mixed normnl snli1w/dt~Xln>Ht~ ove1· n period of 4 hour!'l. Tll(!
malaria should be treated as P. fi1lcipnr11111 mnlnria with objective of loading dose is to provide lhernpculk h•wlH
ACT. The preferred ACT, if available, for mixed malarin as cnrly ns possible In the i.:0111·sc of lrenlmcnl, wJlhout
is either dihydroartemisinin with pipernquine or overshoot to toxic levels. The lond Ing do~c slw11 Id be
arterolane with piperaquine. Primaquine should be used avoided if tlwrc is rl'li11blc l'Vldcncc thnt· tlw p11til'11l h11s
as mentioned above. ren•ivL'd quinilw/h,\lofnntrlnc/mcfloq11lnc In tlw p.1st
24 homs (lrnlofontrine and nwfloqunc prntlucc nddillv!!
Treatment of Comp/leafed Malaria
cardinc toxicity). After the londlng dosu, quin ine J.~
The treatment of severe malaria is an emergency as it is continued at n dose of 10 mg snit/kg ns infusion over
associated with high mortality approaching 20%. If the 2 hours every 8 homs. lntramusculnr quinine is nnothcr
suspicion of malaria is strong then treatment should be alternative for initial thcrnpy if fncilitics for contrnlli·d IV
initiated without waiting for confirmation of diagnosis. quinine administrntion nrc not nvnllnble; sul>cutn11eo11ii
Severe malaria whether due to fokiparum or vivax should ndminslrnlion mny cnusc skin m!crosis.
be treated similarly. Supportive care and treatment of The parnsitc counts start declining- only nftc1· 24 hours,
complications are as important as antimalarial therapy. slo.wer than nrtemislnin derivntives. The patien t Is
Broad spectrum antibiotics are administered if patient is switched to therapy with ornl quinine as soon l\S pos~.H>lc.
in shock or secondary infection is suspected. If parenteral quinine is continued beyond 48 hom~ or If
Treatment should be parenteral as most patients are rennl failure supervenes, the mnintennncc dose should be
not able to take orally and the bioavailability of oral drugs reduced to 5-7 mg/kg to avoid quinine toxicity. Total
is unpredictable. Artemisinin-based therapy is considered
dur.ation of .thcrnpy is 7 dnys. /\ second drug such ~s
superior to quinine in reducing mortality. pynmcthmmne sulphadoxinc, doxycyclinc or cllndamyc10
Artemisi11in-based therapy: Parenteral formulations of ~ho~tld be added. /\ s~nglc dose of primnquinc 0.75 mg/kg
artesunate, artemether and arteether are commercially is given on completion of quinine therapy to crndlc11lc
available; artesunate is preferred. Artesunate is available gametocytes nnd prevent trnnsmission.
as a dry powder which is reconstituted with sodium The only contrnindlcntion to use of quinine Is evidence
bicarbonate and given as a bolus injection. Artemether of sever~ qt~inine ~llcrgy nnd G6PD deficiency. Thrombo·
and arteether are given by the intramuscular route. The cytopenrn, Jatmd1cc, renal failure, hypotcnsion arc not
dose of artesunate is 3 mg/kg in children with weight less contraindicntions for quinine ndministrntion. Minor side
than 20 kg, and 2.4 mg/kg in patients weighing >20 kg. effects including titmitus, dellfncss, headache, nausea and
For artemether the dose is 3.2 mg/kg stat and then visu<1l disturbances (cinchonism) nrc common In consci<>U9
repeated after 12 and 24 hours and then daily. Parasite p<1tients but do not wnrrnnt dose reduclion. Serious side
counts start declining 5-6 hours after institution of effects with parenteral quinine nre rnrc, If It is odmlt1lstcrcd
therapy; asexual parasitemia disappears after mean of 72 properly. Quinine produces prolongntion of the ore
hours. Once the patient is better, a full course of oral ACT interval on the ECG but significant conduction or
Infections and Infestations I 2s9 -
repolar~zation. abnormalities are rare. Routine ECG National Vecto' Bcme Disease Control Programme {NVBOCP]
11\onitonng during quinine infusion is not required, if there The NVBDCP strategies are two folds: Early case detection
iS no evidence of preexisting heart disease. Frequent blood
and prompt treatment and vector control. It has laid out
glucose monitoring .is necessary during therapy. Quinine guidelines for detection and management of malaria.
can cause marked mtravascular hemolysis (blackwater NVBDCP recommends treatment of uncomplicated vivax
fever); c~ange of t~e.rapy to artemisinin derivatives may malaria with chloroquine and fakiparum malaria with
be required. Qumme can cause immune-mediated
ACT. Artemisinin monotherapy is banned in India and is
thrombocytopenia, .which is suspected, if platelet counts marketed only as combinations. Strategies for vector
fail to recover despite clinical improvement.
control include source control, elimination of breeding
Treatment Fa/lures, Recrudescence and Relapse places, biologic control with use of larvivorous fish in
water bodies, and finally chemical vector control by indoor
An optimal response to therapy is defined as counts which residual spray, space fogging and use of chemical
on day 1 are less than day 0, counts on day 3 are <25% of larvicides like abate in water bodies.
count on day 0, no parasites are seen in peripheral blood
72 hours after starting therapy and up to 28 days and there Suggested Reading
is no fever after 72 hours.
• National Vector Borne Disease Control Program, Ministry of Health
Patients with parasitologically confirmed malaria who and Family Welfare, Government of India. Malaria. http :/ I
con~ue to have f~ver .7~ hours after starting therapy are www.nvbdcp.gov.in/iec.html
occas10nally seen m cllnlcal practice. If peripheral smear • WHO. Guidelines for the treatment of malaria. 3rd edn, 2015;
for malaria is negative, the causes include IV thrombo- 1-317. www .who.int/ malaria/docs/TreatmentGuidelines2015.pdf
phlebitis, secondary bacterial infections, coinfections such • WHO. Malaria. http:/ /www.who.int/malaria/areas/treatment/
as typhoid or rarely immune phenomena. If drug overview I en/
resistance is suspected than treatment should be changed
Lelshmanlasls
to either ACT combination or quinine.
Reappearance of asexual parasites within 28 days of Leishmaniasis is a disease caused by parasites of the genus
treatment is defined as recrudescence or late treatment Leishmania, which are transmitted by bites of female
failure. Causes for recrudescence include choice of wrong sandflies. There are three major clinical forms: Visceral
drug, wrong dose, poor compliance or drug resistance. leishmaniasis (VL}, cutaneous leishmaniasis, and muco-
Recrudescence is fairly common in falciparum malaria, if cutaneous leishrnaniasis (espundia). VL and cutaneous
artemisinin monotherapy is used; and in vivax malaria, if forms of the disease seen in India are caused by Leishmania
ACT is used. Treatment of recrudescence includes donovani. Kala azar, the Indian term for VL, denotes
optimizing drug therapy or change to an alternative regime. hyperpigmentation seen in these patients; -200000 cases
are reported annually, most often from Bihar and eastern
n
Control and Prevention of Malaria UP.
Control and prevention of malaria is based on elimination
of the vector by strategies like insecticide spraying, use of Transmission and Etlopathogenesis
insecticide treated bed nets and elimination of breeding The parasite exists in the human or animal reservoir as
places. The latest malaria vaccine RTS, S/ ASOl acts against amastigotes (non-flagellated, oval Leishman-Donovan
P. falciparum. Phase 3 trials on African children, aged bodies) and in the sandfly and culture medium as
6 weeks to 17 months, show efficacy ranging from 18- flagellated promastigotes. In India and Sudan, humans
39%. In holoendernic areas like Africa, chemoprophylaxis are the chief reservoir (anthroponotic cycle). The female
With pyrimethamine sulfadoxine administered twice sandfly (genus Phlebotomus) ingests the amastigotes, which
during pregnancy to reduce prevalence of maternal develop into promastigotes in its digestive tract, migrates
anemia and low birth weight is practised. to the proboscis (salivary glands) and is injected into the
Chemoprophylaxis against malaria is recommended for susceptible host when the sandfly takes its next feed.
travelers from non-endemic areas to endemic areas. Drugs Within the host, promastigotes infect macrophages and
used include weekly chloroquine (for ar~as that are develop into amastigotes. Amastigotes multiply in cells
chloroquine sensitive), weekly mefloqume, weekly of the mononuclear phagocyte system (monocytes, macro-
chl~roquine and daily proguanil, daily ?oxycycline and phages, histiocytes, Kupffer cells and reticuloendothelial
daily atovaquone-proguanil (expensive but safest). cells in spleen and lymphoid tissue).
Prophylaxis should be started at least 1-2 weeks before . Children aged 1-4 years are considered more
departure and continued for 4 weeks after return (except susceptible to the disease. The protective response is
~tovaquone-proguanil where it can be started on :he d.ay primarily cell mediated immunity that results in
~ departure). For travelers to India, prophylaxis with subclinical infection and spontaneous cure in most cases.
either weekly mefloquine 5 mg/kg or daily atovaquone- Failure of immunity results in illness, such that for every
Proguanil is advised. case of VL, there are about 30 subclinical infections.
,
I
11 2so Essentlal Pediatrics
1
Malnutrition and HIV infection also predispose to clinical Tmmunochromotogrnphlc: Htrlp 1111d ELlSA fo
disease. leishmonlnl onll·K39 nnllbndy h111-1 been w~cd tiuccussful! r
for acrodlagnoslf'.I with high 1-1cnHltlv lty (>90%) an~
Cllnlcal Features specificity ( .... 90 1%). Antibody tllcrn lo K39 decrease
Visceral leis11111aniasis: The incubation period is generally following succc1,1Aful lht~ rnpy, nnd lncrcmw during rnlapsl!
3 to 8 months. Features include high grade fever, weight making it o useful tcHt lo recognize lrcn lment failure.
loss, hepatosplenomegaly and abdominal discomfort. Newer methods with high 1:1cnHltlvlty and specificity
There are no rigors and the patient does not appear toxic. inc1ude the detection of LclHhmnnln anllf;cn ond nnllbody
Splenohepatomegaly, with spleen larger than the liver, is in the urine.
usual. Spleen is huge, firm, smooth and nontender and
palpable by end of first month of illness; moderate Treatment
hepatomegaly is seen in -80%. Unlike African VL, Drugs available for treatment of VL In India Include
lymphadenopathy is infrequent in Indian VL (<5%). sodium stibogluconntc, amphotcrlcln U, lipid formulation
Hyperpigmentation of skin is a feature of Indian VL, seen amphotericin 13 nnd miltcfm1lnc. Sodium stibogluconate
in about two-thirds of patients and affecting the face, was considered first line lhcrnpy for VL in India. However,
hands and upper trunk. Progressive emaciation occurs in need for prolonged thcrnpy, advcn;c effects and Increasing
all cases, though appetite is preserved. Cough and resistance are its major Jimitntions. Jn certain areas of
diarrhea are common. Bleeding manifestations in the form Bihar, the resistance rates exceed 50°/i,,
of petechial hemorrhages, epistaxis and gum bleeding may The National V ecl'or l3orne Dh:icnse Control Program.me
be seen. Pedal edema may occur due to hypoalbuminemia, recommends that in areas where s tibogluconate resistance
however, jaundice is uncommon. Diminished cell- rates are more than 10%, amphotcricin 13 deoxycholate be
mediated immunity may account for a high incidence of used. Side effects of amphotcricin include fever, chills,
secondary infections. Pancytopenia and hypergamma- hypokalemia and ncphrotoxicity. Liprn;omal amphotericin
globulinemia are characteristic. B dosed as 1 mg/kg/ day over 3-5 days or a single dose of
The disease may begin insidiously and be asympto- 5 mg/kg is highly efficacious with fewer adverse effects.
matic initially, but usually runs a chronic course that may Indigenous lipid formulntions of amphotericin B (2 mg/
be fatal without or despite treatment. Death usually occurs kg) mixed with 100 mL of 20'1.i fat emu lsion and dosed for
within 2 years in 75-95% cases, because of severe 5 doses approaches success rates more than 90% and at
secondary bacterial infections or gastrointestinal bleeding considerably lower cost, compared to liposomal
in advanced disease. amphotericin Band even stibogluconnte.
Post-kala-azar dennal leishmaniasis (PKDL): A small Miltefosine is an orally active agent. Treatment with
proportion of patients in Africa and India may show PKDL this drug for 3-4 weeks results in cure rates of 95-1 00%,
that develops 1-10 years after resolution of VL. Hypo- comparable to that with nmphotericin. Mild gas tro·
pigmented macular, maculopapular or nodular skin intestinal side effects may be seen. Other effective drugs
1 lesions are seen first in the perioral area, chin and lips,
and later appear over the neck, extensor surfaces of the
arms, trunk, and legs. Lesions spare the scalp, palms, soles,
axillae and perineum. Lepromatous leprosy is a close
differential, but peripheral nerves are spared. Skin lesions
used for treating leishmaniasis include pentamidine and
paromomycin. Recommended treatment regimens are
summarized in Table 11.12.
Severe anemia and thrombocytopenia may necessitate
packed cell and platelet transfusions. The child should
may persist for up to 20 years. These patients may act as receive a nutritious diet, and coexisting nutritional
chronic reservoir of infection. deficiencies should be corrected. Concurrent infections
should be treated using appropriate antimicrobial agents.
Diagnosis
There is pancytopenia, mild elevation of liver enzymes Response to treatment: Fever, sp leen size, hemoglobin,
and hypergammaglobulinemia with reversal of albumin blood cell counts, serum albumin, and body weight are
globulin ratio. The aldehyde test has poor sensitivity and monitored for response to therapy. In most patients, t~e
specificity and is no longer used. fever subsides within 7 days, blood counts and hemogloblll
Definitive diagnosis of VL is usually based on micro- levels rise, the patient feels better, and spleen becomes
scopic detection of amastigotes in smears of tissue smaller within 2 weeks. f'Masitoiogical cure should be
aspirates or biopsy samples. Bone marrow aspirate or documented at the end of therapy by splenic or bone
biopsy is frequently the tissue of choice with sensitivity marrow aspiration. As relapses are common in this disease,
between 55 and 97%. Lymph node aspirate or biopsy patient should be followed for at least 6 months before
(sensitivity 60%), liver biopsy (sensitivity 85%) and splenic considering a definite cure. The spleen may tal<e
aspirates (sensitivity 97%) may also be used. PCR methods 6-12 months to regress completely. Relapse is suggested
on tissue samples and peripheral blood with very high by an increase of ~plcen size, a fall in hemoglobin lcv~l~
sensitivities have been developed. and should be confirmed by the dcmonstra ti on of parasites
Infections and Infestations I 2s1 -
1 Table 11.12: Treatment of visceral leishmanlasls . Amebic dysentery and extraintestinal amebiasis is
OflJ9' Dose Duration associated with high morbidity and mortality and is a
sodium stlbogluconate 20 mg/kg/day IM or IV 28 days major public health problem globally, especially in adults
in developing countries. It is less common in children and
Af11photericfn B 1 mg/kg alternate day 28 days
some estimates suggest that it is responsible for less than
:uposomal amphotericin B 1 mg/kg/day IV s days 3% diarrhea in children <5 years.
Mlltefoslne 2.5 mg/kg/day oral 28 days
pentamldlne 4 mg/kg IV/IM thrice 8 weeks Etlopothogenesls
weekly
The organism exists in nature as a cyst or trophozoite. Each
p~amomycin (aminosidine) 16-20 mg/kg/day IV/IM 21 days
ingested cyst excysts in the small intestine to produce eight
trophozoites that colonize the mucosa of the large
pKDL: Treatment is indicated only for those who have
intestine. Trophozoites may cause tissue invasion and
severe and prolonged disease. Pentavalent antimonials
destruction through several virulence factors, with little
(2-month course) and liposomal amphotericin B are both
effective. or no local inflammation, resulting in characteristic flask-
shaped ulcers, seen commonly in cecum, transverse colon
Prevention and Control and sigmoid colon. Extraintestinal complications occur
when trophozoites invade the bloodstream and migrate
Control of leishmaniasis involves controlling the source through the portal circulation, to lodge, usually in the liver.
of infection and eradicating the vector. Where sand flies
are mostly endophilic (rest mostly indoors after feeding), Clinical Features
spraying houses with insecticide is effective; use of treated
and untreated bed nets is effective where sand flies are Asymptomatic cyst passage is the most common
endophagic (feed mainly indoors). Insecticide treatment manifestation of E. histolytica, in most cases, the infection
of dogs and dog collars is useful where canines are resolves spontaneously, but uncommonly, these
important reservoirs. In India, where anthroponotic individuals may later present with amebic dysentery and
transmission is important, effective treatment of patients, other invasive manifestations.
especially those with PKDL (who act as long-term After a variable incubaton period of weeks to months,
reservoirs), has been found to be effective in controlling about 10% individuals colonized with E. histolytica develop
transmission when combined with vector control. There symptomatic disease, in form of colitis or extraintestinal
is no effective vaccine for prevention of leishmaniasis. disease. Amebic colitis presents as abdominal pain or
tenderness (-80%), with watery, bloody or mucous
Suggested Reading diarrhea. Some may have only intermittent diarrhea
• WHO. Leishmaniasis. http:/ /www.who.int/leishmaniasis/en/ alternating w ith constipation. Fev er is unusual.
• National Vector Borne Disease Control Program, Ministry of Health Occasionally fulminant amebic colitis may occu r, with
·and Family Welfare, Government of India. Operational guidelines profuse bloody diarrhea, fever, widespread abdominal
on kala·azar (visceral leishmaniasis) elimination In India-2015. paU:, diffuse tenderness and pronounced leukocytosis.
http:/ /www.nvbdcp.gov.in/Doc/opertional-guideline-KA- Toxic megacolon, ameboma, cutaneous amebiasis and
2015.pdf
rectovaginal fistulae can occur as complications of
• Aronson N, Herwald t BL, Libman M, et al. Diagnosis and treatment intestinal amebiasis.
of leishmaniasis: Clinical Practice Guidelines by the Infectious
Diseases Society of America (IDSA) and the American Society of Amebic liver abscess is seen in about 1% of infected
Tropical Medicine and Hygiene. Am. J. Trop. Med. Hyg 2017; 96(1): individuals and may occur months to years after infection.
24-45. While some individuals may have concurrent amebic colitis,
more commonly there are no bowel symptoms. The child
Ameblasls
usually presents with fever with chills and rigors and right
Amebiasis is defined as infection with Entamoeba upper quadrant pain of acute onset (<10 days). Examination
histolytica. Clinical features of amebiasis due to E. reveals toxic appearance, right upper quadrant tenderness
histolytica range from asymptomatic colonization to and hepatomegaly; jaundice is unusual (10-15%). Cough,
atnebic dysentery and invasive extraintestinal amebiasis. along with dullness or crepitations in the right lung base
may be present. Complications include rupture into the
EplcJemfofogy
pleura, which has a relatively good prognosis, and rupture
£. histolytica is thought to infect 10% of the world into the pericardium and superinfection with bacteria,
Population, and 2-55% Indians. However, these are which are more serious.
overestimates, because two morphologically identical,
genetically distinct but apparently nonpathogenic spe~ies, Diagnosis
:~ely. E. dispar and E. moshkovskii, are now recognized Diagnosis of amoebic colitis is established by demonstra-
ausmg most asymptomatic cases. tion of motile trophozoites by direct microscopic examina-
II 2s2 ~~~~~~~~~~~~~E~s~se~n~t~la~l~Pe~d~l~at~rl~ca~--~~~------~~~----
~
ti.on of fresh fecal sample. At least 3 stool specimens taken nbdomlnnl pnln ofter 4 doys of ~rcatmcnt), lndivlduai,
on consecutive days should be examined because the test with huge left lobe nbr:tccsses (risk of rupture Into the
has poor sensitivity (<60%; -90% with 3 fresh samples). pcricnrdlum), size more thnn 8-10. cm (F!.uggetitlng
Stool contains plenty of erythrocytes but few leukocytes impending rnpturc) nnd 1:icvcrcly 111 pat1cnt 11 with
unlike bacillary dysentery where leukocytes are plentiful. accelcrntcd clinlcnl course an~ huge nbi;ceRRcs (su~mcstln~
Presence of ingested erythrocytes within trophozoites Is imnlincnt rupture). Aspiration, pcrcutaneow; cathetl!
. h r
pathognomonic for E. histolytica. Presence of cysts of E. drnlnnge, or both, improve outcomes m t e treatment of
histolytica in stool samples is of no clinical significance and nmebic cmpycmn after liver abscess rupture, and
should not be treated. percutnncous cntheter (or, if necessary, sur~ical) ~rainage
Serological tests are routinely employed for diagnosis could be lifesnving in the treatment of amcb1c pcricarditis.
of extra intestinal disease with E. /1istolytica especially for
differentiating amebic from pyogenic liver abscess. Suggested Reading
Commonly used serologic tests in clinical practice are • Cope JR. Ameblmils. Center for Dl11ensc Control and Prev('ntion.
ELISA, IHA and IFA. They are positive in 70-80% patients Yellow Book 2018. https://wwwnc.cdc.gov/travcl/yl'llowbook/
2018 /in fee tious-d isemws-reIn tcd ·to-Ira vel I a mebia sis
with invasive disease at presentation, and in >90% cases
• Fotedar R, Stnrk D, Beebe N, Marriott D, Ellis J, llarkn('ss /.
beyond first week of symptoms. However, they can persist Laborntory diagnostic techniques for En/amoeba sp('Ci('s, Clin
for years and thus are of limited utility in endemic areas. Microbiol Rev. 2007; 20:511-32.
Thus a negative test is more useful than a positive test in • Stanley SL. Amoebiasls. The Lancet 2003; 361:1025-1034.
ruling out infection.
In case of liver abscess, chest radiograph shows elevated Glardlasls
diaphragm and pleural reaction on the right side.
Giardiasis, caused by Giardia larnblia (also known as G.
Ultrasound, CT, MRI, or isotope scan can localize the
intesti11alis or G. d11odenalis), is a prominent cause of
abscess in most cases. Leukocytosis without eosinophilia,
diarrhea in children and in travelers.
mild anemia, raised alkaline phosphatase and high
erythrocyte sedimentation rate are common findings in
Epidemiology
these patients.
The infection is endemic in developing countries with poor
Treatment sanitation. Breast milk protects against giardiasis by virtue
The practice of giving antiamebic drugs for all children of the glycoconjugates and secretory IgA. Individuals with
presenting with diarrhea should be strongly discouraged malnutrition, humoral immunodeficiencies and cystic
since amebiasis is relatively uncommon in young children. fibrosis are particularly susceptible. Children appear to
Metronidazole is the drug of choice for treating amebic be more severely affected than adults.
colitis (dosed at 30 mg/kg/day in 3 divided doses for
7-10 days). Alternatives include tinidazole (SO mg/kg/ Etlopathogenes/s
Suggested Reading
• Shet A. Congenital and perinatal infections: throwing new light
with an old TORCH. Indian J Pcdiatr. 2011; 78:88-95.
• Adachi K, Nielsen-Saines K. Zika clinical updates. Curr Opin
Pediatr 2018; 30:105-116.
Fig. 11.25: Classical periventricular calcification of CMV
HELMINTHIC INFESTATIONS
The diagnosis of congenital CMV is confirmed by a
positive IgM in the first two weeks of life. The sensitivity Helminthic infestations contribute to significant disease
is low and a negative IgM does not rule out CMV. The burden in children in developing countries. Helminthiasis
detection of CMV by PCR on urine or blood is more sensi- is caused by three groups of worms, nematodes
tive. A positive CMV IgM or PCR after the first 2 weeks of (roundworms), cestodes (tapeworms) and trematodes
life can also occur due to postnatal transmission and is (flukes). Nematodes may be further classified as intestinal
not specific for diagnosis of congenital CMV. Antiviral treat- nematodes and tissue nematodes. All these groups differ
ment with ganciclovir is available, but indicated only in significantly in life cycle, mode of infection, pathogenesis
patients with progressive neurologic disease and deafness. and clinical manifestations.
Perinatal HSV Intestinal Nematodes
The transmission of HSV to babies usually occurs during This group includes Ascaris lumbricoides (roundworm),
delivery in mothers who develop primary genital herpes Enterobius vermicularis (pinworm, threadworm),
at that time. Reactivation of genital herpes is associated Ankylostoma duodenale (old world hookworm), Necator
with very low rates of transmission and disease. Infected americanus (new world hookworm), Trichuris trichura
babies may be asymptomatic or have fulminant disease. (whipworm) and Strongyloides stercoralis. These infections
Three forms of disease have been described; that limited are common where hygiene and sanitation are poor and
to skin, eyes and mouth with vesicular eruption, CNS where there is improper disposal of sewage.
disease that presents as meningitis with seizures and
altered sensorium and disseminated disease that presents Life Cycle
as sepsis like illness with high mortality. The latter two Ascaris, Strongi;loides, Necator and Ankt;lostoma inhabit the
may not have associated skin eruption which further small intestine, Enterobius is lodged in the cecum and
complicates diagnosis. Trichuris inhabits the large intestine. Eggs are released in
Diagnosis is by Tzanck smear of the skin lesions, culture the feces with the exception of Enterobi11s where they are
or PCR of lesions or cerebrospinal fluid. HSV serology released on the perianal skin. The eggs embryonate in the
has no role in diagnosis. Neonates with suspected .or environment and become infective. In Ascaris, Entero/Jius
confirmed infection should be promptly treated with and Triclmra, infection occurs by ingestion of embryonated
acyclovir. The dose is 20 mg/kg 8 hourly for 14-21 days eggs. The larvae are released in the intestines and mature
followed by oral acyclovir for 6 month~. Babie~ born to into adult worms locally in case of trichuriasis and
mothers with active primary herpetic lesions dunng.lab~r enterobiasis, while in case of ascariasis they migrate
should be considered for elective cesarean section if through the intestinal wall, into the portal circulation, the
membranes are unruptured. liver, heart, lungs, trachea, swallowed into the pharynx
and finally mature into adult worms in the small intestine.
Congenital Syphilis
In case of Necator, Ankylostoma and Strongyloides infection
5
YJ>hilis is the only maternal infection that is associated occurs by penetration of the skin by filariform larvae,
'With recurrent abortions. Maternal syphilis can be trans- which then through the systemic circulation reach the
Ill 266 -~~~~~~~~~~~~~E=s~s~e~n~tl~a~l!P!e~di~a~tr~ic~s~~~~~~~~~~~~~--~
heart, then the lungs, trachea, pharynx and finally mature enterobiasis, the eggs are pr~sent on the perianal skin from ,........,
into adult worms in the intestines. Strongyloides is unique hi h they can be lifted usmg the scotch tape method 1
among the intestinal nematodes in several respects: Larvae ~o~gyloidiasis, fresh stool should be examined. for la~a~
divide parthenogenetically in the small intestine, as eggs are rarely present; wet mount examination of
development of the eggs into infective larvae occurs within centrifuged CSF and bronchoalveolar lavage may al
. t• so
the intestine leading to autoinfections and retroinfections. help. Peripheral blood exa~ma 1?n may reveal eosino-
philia (striking in Strongylozdes, :1s~eral larva migrans).
Clinical Features In ascariasis, the worms may be mc1dentally observed in
Clinical features depend on the worm burden and vary the biliary or pancreatic ducts by ultrasound or in the
from asymptomatic infection to severe morbidity. intestines during contrast studies of the gastrointestinal
Penetration of the skin by the larvae of Ancylostoma, tract. Serology may also be used to diagnose Strongyloides.
Necator and Strongyloides may cause a maculopapular itchy
rash. Migration of the larvae through the lungs in case of Treatment
ascaris and hookworm may cause Loeffler syndrome All family members should be treated. Antiparasitic drugs
characterized by fever, cough, dyspnea, wheeze, urticaria, available for nematode infections including albendazole
eosinophilia and lung infiltrates. Other causes of Loeffler (200 mg for children aged 1-2 years and 400 mg for those
syndrome include filarial infection, visceral larva migrans, aged 2 years and above, taken with a fatty meal},
schistosomiasis and allergic bronchopulmonary mebendazole (100 mg twice daily for 3 days or 500 mg
aspergillosis. Visceral larva migrans refers to infection by single dose), pyrantel pamoate (11 mg/kg, max dose
dog/ cat ascaris where the larva have an aberrant life cycle 1 gm), ivermectin in a daily dose of 150-200 µg/kg.
and cause prominent visceral manifestations such as fever, Nitazoxanide is a new drug (100 mg for children aged 1-
eosinophilia, bronchospasm and hepatosplenomegaly. 3 years, 200 µg for children aged 4-11 years and 500 mg
Cutaneous larva migrans characterized by an erythe- for older children adolescents) dosed twice daily for 3 days
matous, serpiginous, pruritic eruption refers to infection (Table 11.13). For pinworm, it is essential to stress on
by non-human hookworms where the larva migrate personal hygiene, keep nails clipped short, clean bed linen
through the epidermis and are unable to mature. thoroughly and ensure hand washing before meals.
Ascaris being the largest worm has the most prominent
intestinal manifestations. Heavy infestation can lead to Prevention
vague abdominal discomfort, abdominal distension, Eradication of nematodes is possible only with improved
vomiting, irritability, poor growth and nutritional defi- hygiene and sanitation and appropriate sewage disposal.
ciencies. A large mass of worms may cause bowel There is limited rationale for periodic deworming in
obstruction and migration of the worms can result in healthy children.
cholecystitis, cholangitis, pancreatitis and rarely
intrahepatic abscess.
I
Tissue Nematodes
Hookworms (Ankylostoma, Necator) suck blood from the
intestine and lead to iron deficiency anemia, hypo- Tissue nematodes of significance in India includ.e
albuminernia and edema. The severity of anemia varies Wuchereria bancrofti, Brugia malayi (causes of lymphatic
and with heavy infestations, transfusion may be needed. filariasis) and Dracuncul11s medinensis (guinea \\·orll'I)·
Heavy infestation with Trichuris may cause dysentery, Lymphatic filariasis is endemic in several Indian states,
anemia, rectal prolapse, abdominal pain, distension, chiefly Bihar and Kerala.
hypoproteinemia and growth retardation. Manifestations
of enterobiasis include perianal or vulva! itching caused Life Cycle
by migration of the gravid females to the perianal skin to Humans are infected by bite of the vector which in most
lay eggs. Strongyloides is associated with abdominal pain, instances in India is the Culex mosquito. The bite releases
vomiting, diarrhea, bleeding, steatorrhea and weight loss. the infective larvae which migrate to the lymphatics an~
Ulceration and strictures of the duodenum may occur. grow into adult males and females in about one year. The}
Hyperinfection syndrome due to Strongyloides occurs mate and release thousands of larvae termed as rnicro-
in the immunocompromised (high dose steroids, filaria which stay in the lung arterioles during the daY
chemotherapy, transplant, HIV) and is characterized by and emerge in the systemic circulation at night. They are
dissemination of massive numbers of larvae into various then taken up the insect vector where they develop furth~~
body organs (pulmonary infiltrates, meningitis) gram- and become infective to humans. The life span of the adt
negative sepsis and high mortality. worms is usually 5-10 years but can be up to 40 years·
Diagnosis Cllnlca/ Features
The ~iag~osis of most intestinal nematodes is by The acute symptoms of filarial disease are fev~:~
exammahon of feces for the characteristic eggs. In lymphangitis, epididymoorchitis and adenolymphangt
_,,..--------=~==-=--~~~~------~~l~n~fe~c~tl~o~n!s~a~n~d~l~nf~e~s~ta~ti~o~n!s~~~~~~~~~~~~ 267
i Table 11.13: Treatment. of lntestinal--nematode lntections
·Helminth Primary
Alternative Comment
Ascaris Single dose albendazole
Mebendazole, pyrantel pamoate, Heavy infestation described
ivermectin, nitazoxanide
Hoo1<Worm Albendazole
Mebendazole, pyrantel pamoate lvermectin ineffective
3 day regime of mebendazole better
than a single dose
Adjunctive iron required in most
enterobius Single dose albendazole
Single dose pyrantel or mebendazole Repeat in 2 weeks
(100 mg) Hand hygiene; nails clipped short, bed
linen hygiene
Trichuris Albendazole for 3 days Mebendazole, ivermectin for 3 days Treatment not very effective
Strongyloides lvermectin for 2 days Albendazole twice daily for 7 days Hyperinfection: prolonged or repeated
(not very effective) treatment
cutaneous larva lvermectin for 1-2 days Albendazole twice daily for 3 days
migrans
Visceral larva Antihistaminics and steroids Antihelminthics controversial
migrans Albendazole/ mebendazole
twice daily for 5 days
(Fig. 11.26). In around 0.5% of infected patients a distinct depends on the feeding habits of vector. In case of W.
immunologic reaction to the microfilaria results in an bancrofti, night time collection is preferred. Diethyl-
entity called tropical pulmonary eosinophilia. Features of carbamazine (DEC) can be used as a provocative agent
this condition include cough that worsens at night, to facilitate day time collections. The filarial antigen can
wheezing, low grade fever, enlarged neck nodes, also be detected by immunochromatography-based card
interstitial infiltrates on chest X-ray marked peripheral tests.
blood eosinophilia (more than 3000/ cu mm) and very high
serum IgE levels. This syndrome can also result from the Treatment
pulmonary phase of ascariasis and hookworms, visceral Most of the symptoms are due to the adult worms but
larvae migrans due to zoonotic ascaris and strongyloides paradoxically treatment suppresses or reduces microfilaria
infections. Chronic manifestations of lymphatic filiariasis but does not affect the adult worms. Treatment is usually
seen usually in adults include hydrocele, lymphedema with a single dose of DEC (6 mg/kg) or ivermectin
and elephantiasis. 200 µg/kg and albendazole 400 mg. Corticosteroids may
need to be used to manage allergic reactions of dying
Diagnosis microfilaria. Treatment may need to be repeated every
This is largely clinical and confirmed by dem~nstrating 6-12 months for reappearing microfilaria till the adult
the microfilaria in Geimsa stained thin and thick blood worms spontaneously die. For tropical pulmonary
smears obtained from finger pricks. The time of collection eosinophilia, treatment with DEC at a dose of 6 mg/kg/
I the names reflecting the principal intermediate hosts for The clinical features of cysticercosis depend on the
each of them. Man is the only definitive host for both the location of the cysts and overall cyst burden. In about
parasites. While the pork tapeworm has a scolex with 2 months, the larvae mature into cysticerci of about 2 mm
suckers and hooks that aid its attachment to the intestinal to 2 cm size. Cysts can lodge in the brain, skeletal muscle,
wall, hooks are absent in T. saginata. Taeniasis refers to subcutaneous tissues, spinal column and eyes. The two
intestinal infection by the adult tapeworm, and sites associated with high morbidity are the brain, the most
cysticercosis results from larval lodging in various sites. common (60-90%) location for cysts, and the eye, the ieast
common site (1-3%). Cysts in the brain parenchyrna
Epidemiology (parenchymal neurocysticercosis) cause foca l or
Cysticercosis is the most common parasitic disease generalized seizures and, less commonly, headache, focal
worldwide, with an estimated prevalence of more than neurologic deficits, or behavioral abnormality. Heavy cyst
50 million persons. Neurocysticercosis, the neurologic burden can cause encephalopathy with fever, headache,
manifestation of cysticercosis, is the most prevalent nausea, vomiting, altered mental status and seizures. Cysts
infection of the brain worldwide. in the subarachnoid or ventricular spaces may cause
meningeal signs and symptoms, obstructive hydro·
Pathogenesis cephalus or cranial nerve palsies (by nerve entrapment);
The life cycle of T. solium and T. saginata begins as a larva those located in the spinal column can cause radicular pain
in pigs/ cattle, and human infection is acquired by or paresthesias. Ocular cysts in the subretinal space or
ingestion of these larvae in undercooked pork or beef. The vitreous humor can impair vision by inflammation or
larvae attach to the human gut and grow into adult through retinal detachment, while those in the extraocular
tapeworms. The adult tapeworm sheds proglottids muscles may limit the range of eye movements and
containing hundreds of tapeworm eggs into human feces. those in the subconjunctival tissue present as a nodular
Infections and Infestations I 269 -
010gnosls
'fhe diagnosis of tenias~s is. established by the demonstra-
tion of eggs or proglothds m the stools. Patients may pass
motile segments of worms through anus.
Diagnosis of neurocysticercosis is based on contrast CT
or contrast ~RI of bran:; MRI is superior to CT (Fig. 11.27).
pernonstrah?n o~ a solitary contrast-enhancing lesion less
than 20 mm l~ ?iameter and producing no midline shift
is highly sensitive for neurocysticercosis; if the scolex is
visible, it is pathognomonic. Cystic, nonenhancing lesions
su~ges~ vi~ble, non-degei:erating cysts; cystic, enhancing
lesions md~cate degener~~g cysts with some surrounding
inflammation; and calc1f1ed cysts suggest old cysts that
have already died. Ocular or extraocular muscle cysti-
cerc~sis can be pic~ed. up on CT or ultrasound, or by
detailed ~ye ex~mmahon. Detection of antibodies by
enzyme-lmked 1mmunoblot assay or enzyme-linked Fig. 11 .27: Multiple lesions of neurocysticercosls on brain
immunosorbent assay of the serum or cerebrospinal fluid Imaging
has a sensitivity of 65-98% and a specificity of 67-100%,
varying with the cyst burden, location, and phase of the course for single lesions, though longer courses of 30 days
infection; the immunoblot assay is the preferred test. are preferred for giant or subarachnoid cysts. Use of
Biopsy of the skin or muscle provides a definitive antihelminthic medications is associated with the risk
diagnosis in ambiguous situations, and may be the of an overwhelming inflammatory response from
diagnostic method of choice for ocular, extraocular muscle, degenerating cysts. This can be prevented by giving oral
or painful muscular or subcutaneous cysts. corticosteroids (prednisolone or dexamethasone) for 2-3
days before and during treatment. Intraocular cysticercosis
Treatment should be ruled out before using antihelminthic
Infestation with the adult tapeworm (teniasis) is treated medications as therapy may cause inflammation and
threaten vision.
with praziquantel (5-10 mg/kg once) or niclosamide
(SO mg/kg once). Therapeutic options in neuro- Treatment of subarachnoid and intraventricular
cysticercosis include medications, surgery, or watchful neurocysticercosis is complicated and risky. Cysts in these
waiting. The decision depends upon multiple factors, locations are usually managed surgically because medical
including symptoms and the location, number, stage, and treatment is associated with the risk of inflammation;
size of cysts. Single active parenchymal lesions usually however, recent reports suggest that high-dose albendazole
resolve spontaneously and may not require anticysticercal (30 mg/kg/ day) is associated with clearance of these cysts.
drugs. Watchful waiting is also indicated for calcified cysts A ventriculoperitoneal shunt should be placed in all
because they are already dead, hence children with patients with evidence of significant obstructive hydro-
seizures and calcified inactive lesions on CT do not require cephalus.
specific therapy apart from anticonvulsants. The Surgical removal of the cyst is considered the treatment
commonly used antiepileptics are phenytoin and of choice for intraocular cysts; antihelminthic medication
carbamazepine, which should be continued for at least should be avoided as discussed earlier. Cysts in the
one year and then tapered or continued based on extraocular muscle may be treated with albendazole and
radiologic resolution. steroids, or surgically excised. Isolated skeletal muscle
A meta-analysis demonstrated that ~ysticid~l d~u.g or subcutaneous cysticercosis requires no specific
therapy in patients with multiple and live cysticerc~ 1s treatment unless, it is painful, and then simple excision
associated with reduced seizures and increased resolution may suffice.
of ~esions in the brain parenchyma. Two effective
anticysticercal drugs are available: Albendazole (15 mg/ Suggested Reading
kg/day bid, max dose of 800 mg/day for 7-30 days) or • Kraft R. Cysticercosis: an emerging parasitic disease Am Fam
Praziquantel (50 mg/kg/ day tid for 15-29 days) . Physician 2007; 76:91-6.
Albendazole is more effective than praziquantel. A 7-day • Hawk MW, Shahlaie K, Kim KD, Theis JH. Neurocysticercosis. Surg
course of albendazole is p erhaps as effective as a 28-day Neurol 2005; 63:123-32.
- 270 Essential Pediatrics
• Zamrnarchi L, Bona ti M, Strohmeyer M, et al. Screening, diagnosis are multilocular that proliferate exogenously and alsQ
and management of human cysticercosis and taeniasis: Technical
recommendations COHEMI project study group. Trop Med Int
metastasize.
Health 2017; 22:881-94.
Cllnlcal Features
Hymenolepiasis Symptoms depend on the target organ involved: Very
Infection with Hymenolepis nana, also known as the dwarf often, liver cysts may regress spontaneously without
tapeworm, is very common in developing countries. Man becoming symptomatic. Otherwise, cysts may become
acts as both definitive and intermediate host because the symptomatic after seve~al year.s when. ~igni~icant mass
entire life cycle may be completed in human host; effect results in abdominal pam vom1tmg, increase in
however, rodents, ticks and fleas may serve as the abdominal girth and a palpable mass; jaundice is rare.
intermediate host. The infestation usually results from Alveolar cysts have a more malignant course. Direct
poor h~gi_ene: The. adult worm lives in the jejunum. spread of infected tissue may result in cysts in the
Transnuss10n is mainly feco-oral, but autoinfection may peritoneal cavity, kidneys, adrenal gland or bones. Lung
also occur, such that one host may harbor upto thousands cyst may present with chest pain, cough, hemoptysis and
?f ad~lt w~rms. Symptoms are usually non-specific, breathlessness. Involvement of the genitourinary tract may
mcludmg mild abdominal discomfort, poor appetite and manifest as passage of cysts in the urine (hydatiduria) and
cosmophilia, some show growth retardation. The infection hematuria. Rupture or leakage from a hydatid cyst may
is a major cause of eosinophilia. The diagnosis is based cause anaphylaxis, manifest as fever, itching and rash, and
on the demonstration of characteristic eggs in stools. results in dissemination of infectious scolices. Rare but
Treatment is with praziquantel (25 mg/kg once) or potentially serious complications include compression of
niclosamide (50 mg/kg once, maximum 2 g). important structures in the central nervous system, bone,
heart, eyes or genitourinary tract.
Echinococcosis (Hydatid Disease)
Diagnosis
Human echinococcosis is an infestation caused by larval
stages of members of the genus Echinococcus, and is Physical examination may reveal a palpable mass, hepato-
characterized by production of unilocular or multilocular megaly or subcutaneous nodules. Ultrasonography is the
cysts in the lung and liver. Echinococcosis is endemic in most valuable tool in diagnosing echinococcal cysts. Lung
most continents of the world, with hyperendemic areas hydatids may be visible on plain X ray. MRI and CT may
in Western China, North Africa, West Asia and areas of be used for further delineation (Fig. 11.28). Diagnostic
South America. aspiration is generally contraindicated because of risk of
infection and anaphylaxis. Antibody detection by EUSA
Pathogenesis is more sensitive but less specific. The test uses partially
Hydatidosis is a zoonosis caused by two Ecltinococcus purified antigens that cross-reacts with other parJsites
species, E. granulosus and E. mulilocularis. The parasite eggs such as cysticercosis and schistosomiasis.
are transmitted from members of the canine family like
Management
dogs and wolves, to various wild and domestic animals
like sheep, cattle and goats, which act as intermediate Treatment depends on the stage and location of the lesion,
hosts. Humans are accidental hosts. Eggs from the adult ~d importantly the experience of the treating center and
worm are passed in the stools that may contaminate the includes albendazole, surgical excision or PAIR
water and soil, and also the fur coats of dogs. Ingestion of (percutaneous asi:'i~ation, instillation of hypertonic sJline
food or water contaminated with eggs or direct contact or another scohc1dal agent; and reaspiration after
with infected dogs may result in humans being infected 15 minutes).
accidentally. Eggs hatch in the intestines to release larvae
that penetrate the intestinal mucosa, and traverse the Suggested Reading
venous or lymphatic system to reach the liver, lungs and, • Cze1'.1ak BY, Akhan 0, Hiemetzberger R, et al. Echinococcosis of
less commonly, other target organs. the hver Abdom Imaging 2008; 33:133-43.
In the target organs, larvae develop into characteristic • Na~arro LE, '.'~ Z, Chiodini PL. Current management of cystic
echinococcos1s. Chn Infect Dis 2015; 60:721-8.
multiloculated fluid-filled cysts, called hydatid cysts. In
children, lung cysts are common, whereas in adults, cysts
are more commonly seen in the right lobe of the liver. RATIONAL ANTIMICROBIAL THERAPY
Other tissues that may be involved include bone, brain, AND ANTIMICROBIAL RESISTANCE
genitourinary tract, intestines and subcutaneous tissue. Rational antimicrobial therapy refers to using anti·
The cyst may keep on expanding over several years. rnicrobials only when indicated; the right drug for the right
Life cycle of E. multilocularis is the same except that duration through the right route and in the right dose.
rodents and mice serve as intermediate hosts, and the cysts Irrational use of antibiotics compromises treatment
Infections and Infestations I 211 -
Solutions
• Education of medical practitioners about rational
antimicrobial practices from the undergraduate level
through postgraduation and for practicing doctors.
• Development of evidence-based guidelines to treat
common infections and ensuring that they are
implemented.
• Educating the public and parents about the hazards of
overuse of antibiotics
• Legislation to prevent over the counter availability of
Ag. 11.28: Lorge hydotid cyst of the liver antimicrobials and licensing of irrational fixed drug
combinations
• Preventing overuse of antimicrobials in the veterinary
outc~mes, increases ~d~erse_ effects and cost of therapy.
Irrational use of antimicrobials is the biggest driver for industry
antimicrobial resistance. Rising antimicrobial resistance • Establishing antimicrobial stewardship programs in
is responsible for increasing morbidity, mortality and hospitals targeting use of antimicrobials in inpatients
treatment cost of infections. especially intensive care units.
The most important antimicrobial resistance challenges Suggested Reading
are:
• Marston HD, Dixon DM, Knisely JM. Antimicrobial resistance.
• Resistance in gram-negative bacilli due to production JAMA 2016; 316:1193-1204.
of extended spectrum beta-lactamases and carba-
. penemases (New Delhi metallo-beta-lactamase) HEALTHCARE-ASSOCIATED INFECTIONS
• Multidrug-resistant tuberculosis AND INFECTION CONTROL
• Chloroquine-resistant falciparum malaria
Healthcare-associated infections (HAis) are termed as
• Resistance in HlV.
those infections that occur in hospitalized patients and
Examples of Irrational Therapy were neither present nor incubating at the time of
admission. They include those infections that occur as a
• Prescribing antimicrobials when not indicated, e.g. result of hospital visit (varicella following exposure in the
using antibiotics to treat viral upper respiratory tract emergency room or outpatient visit), or in hospitalized
infections and viral gastroenteritis patients (diarrhea) or health care personnel (see Chapter 28).
• Prescribing multiple antimicrobials at the same time,
irrational combinations and changing them frequently Types of HAis
• Using high end antimicrobials such as carbapenems to These may range from minor infections such as viral upper
treat community acquired infections and using drugs respiratory tract infections, diarrhea to serious infections.
for MRSA such as vancomycin when not indicated. Immunocompromised children, those in the intensive care
• Using fewer drugs than indicated for diseases such as unit and those who undergo surgery are at the greatest
tuberculosis, HlV, malaria. risk for serious infections. These infections include central
line-associated bloodstream infections (CLABSI), health
Causes care-associated pneumonia (HAP), catheter associated
• Practitioner errors due to inadequate knowledge about urinary tract infections (CAUTis), surgical site infections
microbial etiology and resistance patterns. Other (SSis) and C. difficile associated diarrhea.
reasons are fear of missing a diagnosis, in order to
circumvent investigations and sometimes due to Etiolow of HAJs
pressure from parents. The wrong belief th~t. use of The etiology of health care associated infections in India is
newer and multiple antimicrobials is beneficial also predominantly resistant gram-negative bacilli including
drives practitioners to over use antibiotics. . ESBL (extended spectrum beta-lactamase), AmpC beta-
• Self medication by parents and as per pharmacist lactamases and now even carbapenamase producing E.coli,
recommendations Klebsiella, Pseudomonas and Acinetobacter spp. Gram-positive
• Aggressive marketing of antimicrobials by pharma- pathogens including S. aureus and enterococcus are less
ceutical companies common. Candida is emerging as an important pathogen.
~- - -
- 272
B11onun1 Podlnlrlo•
C/lnlcal Mon/festottons
---....
1:omblnttllom1 rl\tch ru1 plpornalllln tn1.0bnct1Hn or
The clinical. nHmifostotlontl lndudl! new UIHH!l fl'Vl't\ cdop1•rnv.onu r111lb1wl1rn1 or rr1rh11p1•n1~ mA with or Wilhoui
h~modynanuc c~mpromlsc, respiratory ddl'tforc1llo111md tlll\lkttl'ln '1tld 1H1tlf1111H1llr1, r11 COl'lilln ICUtt With hlgl1
diarrhea d~pcndmg on the site l)f 1-11\11-1. StHllL' of the I lt\lti prnvtlluncu of t~11rhnp1•1wrn rot1i11lnni:1•, cullRlln m11 y b
can ~e rapidly prog1~cssivc cmd lc(ld lo ~L·plk iil11ld.: '"'" 1wmlud. Sm1rco c1~nlr11I ttrn'h tlR romovnl of lnfoctt•cl lloc:
multiorgan dysfunction in i\ few hours. l-11\ls l\l'l'd lti bi' nnd d1·11llH1Ht' ol ptrn IR c ru ~ lfll. In l'lw lnlor 'RIR of
differentiated from non·infcclious cnuscs of fever slid\ iltl nntlmkrnhl,11 Hll'W11rdtthlp, lht1rnlti of do-m1cnlf1tlon ;)nd
drug fever, thrombophlcbitis, puhnunary L'mbollsm ,md opllml:.<.11lhm of llwmpy nl ·Hi- 72 ho11rn onc11cull111·0 results
atelectasis. Mere isolation of bacll'ria from 11011 1-ilL't'i ll~ llilL' i\l'O nvttllnblc l:onn11t bu ovurumphn fl lzcrl.
cultures such as trnchea, ul'inc, stool nml dr11lm; I~ nnl
indicative of HAis nnd should not bl.! trci\lcd. r)rovo11 flon
Infection I rcvcntlon nnd control 1!-1 lhc co rdlnnl f'l trntcgy
Consequences of HAis lo prcvml I IAl's. Thu mosl lmporlnnt la lrnncl hygiene wllh
HAis can lead t? significant morbidity, mmlt1llly 1\nd nnllmkrnufnl sonp nnd wnllll' 01· nlcohnl-bnRcd hnnd rub
~engthen duration and cost of hospitnl stny. Mure bcfol'l' nnd nflcr u11ch pnlfonl· rnnlncl, before sterile
unportantly they lead to incrcnsc use of high end pr0l:cd11n.•s nnd nftcr contncl with pnlft•nt surroundings.
antimicrobials that fmther amplify the problem of lmplllllll'llllni.; prcvcnlfon bundles for CL/\1351/ HAP/
antimicrobial resistance. CJ\UTI 11nd SS1 nrc inlcgrnl to nny Infection control
progl'llm. Mnlnlninf ng 11 clcrm hospilni environment with
Treatment nllllnlion lo nit· nnd water qunlf ty and following standard
Management entails early recognition and sending nnd tl'llnsmlssfon bnscd prccnul'lons ore other componenls
appropriate cultures including blood, cndotrnchcnl of prcvcnl'lvc strategy.
aspirates, urine and pus, and starting brond·spcctrum
Suggeste d Reading
antibiotics pending reports. The choice of antibiotics vnrics
with the severity and site of infection, prior antibiotic • Poster CD, Snbclln C. Mcnll'J1 c11rc-nHiioclntcd Infections in rhildrcn.
JAMA 2011; 305:1480-81.
exposure, local antimicrobial resistance patterns and host
• l'nlrlck SW, Kwnl AT, Klclnmnn K, cl· ol. I-!cnllh care-associated
comorbidities such as renal/ hepatic dysfunction. Usually inrccllons nmong cl'lllcillly ill chlldrcn In the US. Pctlintncs 2014;
this regime comprises beta-lactam-betalactamase inhibitor tJ.1:1-10.
12
Diseases of Gastrointestinal
System and Liver
Anshu Srivastava • Barath Jagadisan • Surender K Yachha
5 episodes in all or 3 episodes during a 6-month period. 24 hours ambulatory esophageal pfl monitoring is a
Typically, the attacks begin in early morning with validated method for quantitative measurement of
symptoms of autonomic surge, e.g. lethargy, pallor, mild esophageal acid exposure (Fig. 12.3). It is also used to
fever, headache, tachycardia, hypertension, diarrhea and evaluate the efficacy of anti-secretory therapy and to
abdominal pain. Most subjects have onset in preschool or correlate symptoms (e.g. cough, chest pain) with acid
school age. Family history of migraine and/ or motion reflux episodes.
sickness is noted in 30-40% cases. Symptoms may overlap
with abdominal migraine. Combined 24 hours multiple intraluminal impedance and
pH monitoring detects acid, weakly acid and nonacid
Management: Known precipitants of the episodes should reflux episodes. It is thus superior to pH monitoring alone
be avoided. Management of an attack includes providing which detects only acid reflux episodes. Its main utility is
a quiet environment, administration of intravenous fluids, to evaluate the temporal relationship between symptoms
use of serotonin 5-HT3 antagonists such as ondansetron and GER episodes.
(0.3--0.4 mg/kg/ dose IV q 4-6 hr up to 20 mg) and sedation
with Iorazepam (0.05-0.1 mg/kg/ dose IV every 6 hr) . Upper GI endoscopy may show erosions or mucosal breaks
Agents recommended for prophylaxis against future in the distal esophageal mucosa, the most reliable evidence
attacks are cyproheptadine (0.25-0.5 mg/kg/ day in two of reflux esophagitis. Mucosal erythema and pallor are
or three divided doses) in children below 5 years and, in highly subjective and nonspecific findings. Complications
older children, amitriptyline (initiate at 0.25-0.5 mg/kg/ day like stricture esophagus (Fig. 12.4) and Barrett's esophagus
at bedtime; may increase up to maximum of 1.0-1.5 mg/ can be picked up at endoscopy. Histological features like
kg/day) or propranolol (0.25- 1 mg/kg/day; up to 10 mg elongated retc pegs, basal cell layer hyperplasia and
q 8-12 hr). dilated intercellular spaces, alone or in combination, are
suggestive of reflux esophagitis.
Gostroesophogeal Reflux Disease (GERD) Endoscopic biopsy is important to evaluate other causes
Gastroesophageal reflux (GER) is passage of gastric of esophagi tis and to diagnose Barrett's esophagus. While
not useful for the diagnosis of GERO, barium contrast
contents into the esophagus with or without regurgitation
radiography helps rule out anatomic abnormalities of the
and vomiting. GER is a normal physiologic process that
upper gastrointestinal tract that may cause symptoms
occurs several times a day in healthy infants, children and
similar to those of GERD. This investigation should be
adults. When this reflux of gastric contents causes
done in all infants with vomiting.
troublesome symptoms and/ or complications, it is known
as GERO. About 50% of healthy 3-4-month-old infants Nuclear scintigraplzy has a role in the diagnosis of
regurgitate at least once per day and most of them outgrow pulmonary aspiration in patients with chronic and
this by 1 year of age. Follow-up studies suggest that infants refractory respiratory symptoms due to GERO.
with persistent spitting beyond 3 months of age are at an
Empiric trial of acid suppression: Using proton pump
increased risk of developing GERO in childhood. Children
I
inhibitors for up to 4 weeks is justified in older children
with obesity, repaired esophageal a tresia, cystic fibrosis,
or adolescents with typical symptoms suggesting GERO.
hiatal hernia, preterm babies and a family history of GERO
are at risk of developing severe chronic GERO. Management: Treatment of GERD depends on patient's
Neurologically impaired children like those with cerebral age and nature and severity of symptoms and includes
palsy have increased risk of severe GERO due to multiple lifestyle changes, pharmacologic therapy and surgery.
factors like low pressure of the lower esophageal sphincter Lifestyle changes: Infants should be placed in left lateral
and predominant supine position. position with the he ad end elevated by 30° in the
Clinical features: The common symptoms associated postprandial period to reduce the frequency of reflux. Cow
with GERO in children are: (i) recurrent regurgitation; milk protein allergy is sometimes a cause of unexplained
(ii) weight loss or poor weight gain; (iii) irritability (in crying and vomiting in infants. Therefore, fo rmula-fed
infants with recurrent vomiting may benefit from a 2-4
infants); (iv) h eartburn or chest pain (older children);
weeks trial of an extensively hydrolyzed protein formula.
(v) hematemesis, dysphagia and odynophagia (if
Infants with inadequate weight gain because of losses by
complicated by esophagitis or s tricture esophagus);
regurgitation may benefit from increasing the energy
(vi) wheezing, stridor, cough and hoarseness; and
density of formula . Careful follow-up with charting of
(vii) Sandifer syndrome, an uncommon manife~tati?n,
caloric intake and weight gain is essential.
characterized by spasmodic torsional d ystoma with
For children and adolescents with GERO, measures that
arching of the back and opisthotonic posturing.
are useful include: Dietary modification (to avoid caffeine,
Evaluation: A detailed history and physical examination chocolate and spicy food s), weight loss if obese, sleeping
are generally sufficient to establish the diagnosis of GERO. in the left lateral position with elevation of the head-end
Useful investigations are as follows: of the bed, avoidance of alcohol and cessation of smoking.
- 216 1 ~~~~~~~~~~----.!e~1~1~on~t~
ln~l!P~od~ln~t~rl~o•~--------------------~--------...
Erect
supine
9.0
8.0
7.0 •• I · •kU• ..•11n.u1 l •l llil 11o..11u1.111.11, 11u n 1truu1.n1111111u 11111u1n111n Ullllfll llilll
1
6.0 • •1' ·"'"···••••U·•··••I u.~, .. ,_.. ..... u11u~uu.11h1MwUt:11111uuAt11u1w-u"1: ' " '"'"' •n:n UllU• " '"
5.0 " ' "" .. . . .. 1.uh •• 11 ... _ ,._u ... . . .u .,.;a o ou .t 11.u 1u•11l4UUll •llUUCU• •Ull UIU IU l l f- J,UI Ullh 1
1 1111
• • ,..,,,lf, ,...,,.,,
pH 4.0
3.0 .......,,_ . _ . ............_ _ , ......... . . . .... .......1...........""·• ·UU.• \AAl ooo.10u ...111:.u...1u1<11u111111•1• u 11ou t11ru u 1 1111111HllllU•UU IHOtlff• l•U •H,,l l URU/ll nn<'t<llH
2.0 .._ ,...,.," ....' " .... ,..._• .,,..........., _ , , ,.... ,, , , , ..,, .. " " ' " "''°uu1u ii. 11 1 u1 1 11 , 0 1 u1 11n1uuu11n o11111 1110 11u1 u 11•1111i1,.u1n11•1111•11111111ou-1uuruiu11111u trJ1l ll
1
1.0 _,_,.....,,,....u_,,..,,,_, 1hnU••""'" '''" "'nlhll••"'•""•l••-o... .-iutn~Ul.ll nHUU•ll UOUUllUlllf•l •n 1111 111u1111111u"-u111uu111u111•u1t'11flfl
0.0 ~~~-,-~~~--~~~-p~~---11~~~--r~~~-r
Erect
supine
9.0
8.0
7.0
6.0 ....... .............. .... ........ .....,.,....... . """
5.0
pH 4.0
3.0
2.0
1.0
0.0
12:00:00 PM 4:00:00 PM 8:00:00 PM 12:00:00 AM 4:00:00 AM 8:00:00 AM
Fig. 12.3: 24 hours esophageal pH study. Upper panel shows a normal study and lower panel shows frequent episodes of acidic
reflux with drop In pH to <4 suggestive of GERO
pressure, decreasing the number of episodes of tr.m:sient Th~ mlln C..lU~"S ,\re \;.~~br',\l f'\l~y. b\llb,\r rulh.H\\)'l'\ltl~.
}Dwer esophageal sphincter relaxation and ~g ~ mu..~a.r d~~trophy. bt\lu~tl'm tul\Hl~ ill\d l\l'UNp,\thy.
nadir pressure during sv..·allow-induced rela.'\'.ation.
increasing the length of intra-abdominal esoph.3gus, Esopl:ugc11l 1f~:"J'l111giit: This lJ~~un; dul' ttl cnmlltlon~
accentuating the angle of His and reducing a hiatal hernia. im-ahing e~Fh,l~"'\.'\\l rh,1::1..• \)f sw~\k"dn~ l.t.'.1..'\Xll\llrl<\tl'd
if present Antireflux surgery may be of beneiit in 5el&."fed pt?ristalsis l.)f ~s"1ph,\~Nl blidy with simultilll~lHI~
children ·with chronic-relapsing GERD ,,;th intractable relaxation ot LES, Eti1..,\ll~\' l.lt 1..'::l>rh•\~l·.1l dysphngln cim
symptoms or risk of life-threatening complications. be broJ.dly di\·idt.'\.'l into hn1 ~n.1up::: ~ llltOr 1..\\llSl's (q;.
.achalasia -:ardiJ. .md dHfusl' l'Sl1plM~1..·.1l sp.1sm) nml
Suggested Reading structur,1l ~..m~ l~·S· strktu~s. fordgn bl1dy1 Seh11tikl'~
• Ll BU, Lefevre F, Chelimsky GG, et al; ~orth -~~.,.._~-fur ring,es-0ph.1o~l w~b, t'\..~tnl.)philk t.'Soph.1gitis nnd c.\lri1'5lc
Pediatrk Gastroent.erology, Hepatolc>gy zn.d X-utrition. C~ rompressicn by ,\~rr,mt n~~l or mcdinstin;1\ m01~).
statement on the diagnosis and ma."lagemel'.t oi qdic '\""cmiti."1.g
syndrome. J Pediatr Gastroe:nterol J-,."utr 200S; ~:Ji-93. Dlfferen::: D:og.."lOS.:S end f\toluatfon
• Gastroesophageal reflux: management guidelines for the
Pediatrician. Pediatrics 2D13; 13l;e16SH693. The imp<>rtant 1:~ms~s of d~~phagiJ nnd thdr ~\'nluntion
are shown in T.lbl~ 12.2 ns well ns discussed bdow.
Dysphagla
Dysphagia refers to a sensation of food being hindered in Congenit.ll csop1111St'11l stcnosis: This may be of lhrel'
its passage from the mouth to the stomach, i.e. diffi.cultv types: \\ eb or di.1phr,1gm, fibromus~u\,u stenosis and
in swallowing. Odynophagiil is painful swallowina and stenos.is dut- to c.1rtilaginous trni..:ht'obronchb\ rl.'mnnnt:;.
globus is the sensation of a lump in the throat. Dysphagia Symptoms of Yomiting or dl~st infection due to .1spiration
can be divided into two distinct groups: typically dewlop around 6 months of .1ge whl.'n w eaning
is started.
Oropharyngeal or transfer dyspliagia: Presence of droolina
choking, coughing and nasal regurgitation suggesfs Foreign boifies in ~so1•l111gus: Sharp foreign bodies nnd
oropharyngeal dysphagia. Disorders involving chewing, batteries can ca.use damage by perfor\ltion S\.'Condnry to
oral transfer or pharyngeal phase of swallowing cause this. pressure or chemical necrosis and C\ln presl.'nt with
Table 1U: Evaluation and manage~ent of ~sophageal lesions that cause dysphagia
\ Etiology Investigation Rnding Treatment
Corrosive (acid or alkali) Barium swallow and meal; Narrowing in one or multiple, Endoscopic dilatation (Balloon
stricture upper GI endoscopy short or long, segments of or Savary-Gilliard dilators)
esophagus; may show
contracted stomach or
pyloric stenosis
Stricture after repair of Barium swallow (Fig. 12.5) Narrowing of a short Endoscopic dilatation
tracheoesophageal fistula segment of esophagus
Congenital stricture Barium swallow; CT chest Stricture in middle or Endoscopic dilatation or surgery
lower esophagus; carti·
laginous tissue in
stricture
; Postsclerotherapy stricture Barium swallow; upper Narrowing in lower end Endoscopic dilatation
GI endoscopy of esophagus
· Peptic stricture Barium swallow; Narrowing in lower Endoscopic dilatation; proton
endoscopy; 24 hours pH esophagus; may pump Inhibitor after dilatations
. I
study show hiatus hernia or
erosions
Foreign body Plain X-ray; upper GI Type of foreign body Endoscopic retrieval
endoscopy (Fig. 12.6) and site of impaction
• Achalasia cardia Barium swallow; endoscopy Beak-like narrowing In Pneumatic dilatation; Heller's
esophageal manometry lower esophagus cardiomyotomy
Infectious esophagitis (in Upper GI endoscopy; White curd-like deposits Fluconazole (Candida); ganclclovlr
lmmunocompromlsed children) endoscopic biopsy (Candida); ulcers (cyto- (cytomegalovirus) or acyclovir
megalovirus, herpes) (herpes)
GI: Gastrointestinal
- 278 Essential Pediatrics
Fig. 12.5: Post-TEF stricture. Black arrow shows the short stricture Fig. 12. 7: Barium swallow showing achalasla cardla
and white arrow shows the dilated proximal esophagus
feeding aversion with failure to thrive. The onset is gradual
and the average age at diagnosis in children is around
8-9years. The barium swallow shows esophageal dilatation
with beak-like narrowing at the LES (Fig. 12.7). Manometry
is the most sensitive and specific tool and shows absent
peristalsis in esophagus; incomplete/ absent LES relaxa-
tion and raised intraesophageal pressure. Endoscopy is
useful to exclude other etiologies of dysphagia.
Endoscopic pneumatic balloon dilatation and Heller's
cardiomyotomy with antireflux procedure are two main
therapeutic modalities. The experience with per oral
endoscopic myotomy (POEM) is limited.
Suggested Reading
• Gariepy CE, Mousa H. Clinical management of motility disorders
in children. Semin Pcdiatr Surg 2009; 18:224-28.
• Pandolfino JE, Gawron AJ. Achalasia a systematic rcvkw ..lAl\!A
2015; 313:1841-52.
Constipation
Constipation is defined as a delay or difficu lty in
Fig. 12.6: Upper GI endoscopy showing foreign body (coin) in defecation, present for 2 or more weeks and suffici::>nt to
esophagus cause significant distress to the patient. It is incrcn . ingly
being recognized as a very common problem in child~en
dysphagia, rnediastinitis and/ or upper gastrointestinal and is associated with both physical and psychologica:
bleeding. The vast majority of foreign bodies pass morbidity and a poor quality of life. The normal st~o
unimpeded through the GI tract. The most frequent sites frequency decreases from 4 or more per day dunng
of impaction are at the cricopharynx, mid esophagus at infancy to once per day at 4 years of age. A stool freq.ue;~y
tracheal bifurcation and just above the LES. of ~2/week is considered abnormal for all ages. .e
Guidelines recommend that no foreign body should be majority of patients have functional constipation; orgaruc
left in esophagus for more than 24 hours. Endoscopic removal cause is found in -15% (Table 12.3).
under sedation or anesthesia is the standard of therapy.
Achalasia cardia: Children present with dysphagia, Approach f
vomiting, weight loss, respiratory symptoms and slow Details about pattern of stooling, time of first pass:~~i~e
eating whereas toddlers present with coughing and meconium, presence of blood in stools, diet, stress u
Diseases of Gastrointestinal System and Liver
1219 -
Table 12.3: Causes.of constipation · Ma11ageme11t: No investigations are required for diagnosis
Intestinal nerve/muscle disorders: Hirschsprung disease, in the majority of children with functional constipation.
intestinal neuronal dysplasia, pseudo-obstruction, spinal cord However, an X-ray abdomen may be done to document
abnormalities (tethered cord, myelomeningocele) impaction in select situations, e.g. an obese child who is
Anorectal: Anteriorly placed anus, anal stenosls, rectal stricture, not willing for a per rectal examination. Two main steps
pelvic mass (sacral teratoma) in the management are disimpaction and maintenance
Systemic disease: Hypothyroidism, celiac disease, diabetes therapy.
lnsipidus, diabetes mellitus, hypercalcemia, cystic fibrosis,
myotonic dystrophy
Disimpaction is required in patients who have a rectal
impaction, i.e. presence of a large hard mass of feces on
Developmental: Mental retardation, autism
per rectal examination or abdominal fecoliths or retentive
Drugs: Opiates, anticholinerglc agents, phenobarbltone, encopresis. Rectal impaction is responsible for progressive
vincristine, lead
dilatation of the rectum over time and increased threshold
volume for rectal sensation and defecation. This 'clean out'
events, drug intake and previous surgeries should be known.
is essential, if maintenance therapy is to be effective. The
A predominantly liquid and low fiber diet (milk based) is
oral route is preferred over rectal as it is less invasive.
common and contributes to constipation. A complete
Total bowel wash is done to clean the entire colon using
physical and neurological examination is essential.
Examination for features of spina bifida (pigmentation or polyethylene glycol (PEG) in a dose of 1.5 g/kg/day for
~days at home. Alternatively, PEG electrolyte solution
tuft of hair on lower back), power in lower limbs, perianal
sensation, voluntary contraction and tone of anal sphincter can be given in the dose of 15-40 mL/kg/hr till the rectal
and amount and consistency of stool in rectum on per output is clear and devoid of solid fecal material. In young
rectal examination are extremely useful for diagnosis. children, this should be done using a nasogastric tube and
in hospital under supervision. Intravenous fluids may be
'Red flags' like failure to thrive, blood in stools,
required in small children to maintain adequate hydration.
recurrent fever with loose stools.(enterocolitis), recurrent
An alternative to oral administration of PEG is the use of
vomiting, lump in abdomen, recurrent chest infections and
phosphate enema (contraindicated in <1-year-old) or
features of hypothyroidism should alert the physician to
sodium dioctyl sulfosuccinate enema, 30-60 mL/10 kg
suspect organic etiology.
body weight to a maximum of 120 mL, once or twice
daily for 1-2 days. Repeated rectal enemas should be
Functional Constipation avoided.
The increase in intake of low residue diet and sedentary The aim of maintenance therapy is to promote regular
lifestyle is responsible for the increase in functional stooling and prevent reimpaction. Success of this therapy
constipation in children. Functional constipation is defined is defined as passage of 1-2 soft stools per day and no
by the presence of at least 2 or more of the following soiling. It includes the following components:
criteria: (i) two or fewer defecations in the toilet per week;
i. Behavioral training involves establishing a positive
(ii) at least 1 episode of fecal incontinence per week;
routine of sitting on toilet for passing stools after meals
(iii) history of retentive posturing or excessive volitional
stool retention; (iv) history of painful or hard bowel regularly (2-3 times per day for 5-10 min) and
movements; (v) presence of a large fecal mass in the documenting all stool passage. Embarrassment or
punishment should be avoided.
rectum; and (vi) history of passage of large diameter stools
that may obstruct the toilet. ii. Dietary changes: A nutritious diet with fruit/vegetables
Children with functional constipation pass large or hard and adequate fluids is given. A short trial of milk and
stools and display stool withholding behavior, milk product free diet may be done in refractory cases
characterized by stiffening of whole body and screaming suspected to have bovine milk allergy.
in infants, to walking on tiptoes or tightening of buttocks iii. Medication: Regular and tailor-made (as per response)
in older children. This is often misunderstood by parents laxative use is the key to success and this should be
as if the child is trying to defecate. Often an acute illness, explained to the family. Osmotic laxatives, like
change in diet, coercive toilet training or non-availability lactulose (1- 3 mL/kg/day), and PEG (0.8-1.0 g/kg/
of clean toilet leads to non-passage of stools. The stools day), are the first-line agents. Stimulant laxatives like
become hard and cause pain on passage which leads to senna or bisacodyl are to be used only intermittently
association of defecation with pain and withholding. This as a rescue therapy to avoid impaction. Prokinetics like
further increases stool size and hardness with more pain cisapride are not recommended. In infants, mineral oil
on defecation. Children with functional constipation have and stimulant laxatives should not be used. Glycerin
abdominal pain (10-70%), anorexia (10-25%), enuresis or suppository is preferred over enema for impaction in
urinary tract infections (30%) and psychological problems infants. Premature withdrawal of medications is a very
(20%). common cause of relapse.
- 2so 1
Fig. 12.8: Colonic transit s1udy showing retained radlopaque Fig. 12.9: Barium enema showi 01ack
mar1<ers in the left colon suggestive of outlet obstruction In a arrow shows the dilated ng Hlrschsprung disease. w
child with consflpotion shows the tr tt· proximal segment and white arro
ans ion zone
Diseases of Gastrointestinal System and Liver 1201 -
I
close to the anal margin. Effort is made to preserve the anal the overlying abdominal wall. Thus, the pain of
canal and sphincter mechanism, thu~ preserving con~ence. appendicitis is referred to the periumbilical area when the
In patients with delayed presenta~o~~ a colosto~y m the inflammation is restricted to the visceral peritoneum, but
ganglionic bowel is performed 1mhally to. reheve. the is perceived in the right iliac fossa when the inflammatory
obstruction and allow the dilated hypertrophied proXlmal fluid comes in contact with the parietal peritoneum. Pain
bowel to return to normal. Subsequently, definitive surgery arising from retroperitoneal structures is referred to the
is performed. Now less invasive, laparos~opic and s~gle back as it is sensed by the somatic nerves in the posterior
staged surgeries are performed, in companson. to .previous abdominal wall. Referred pain is common in abdominal
2-3 staged procedure. In the long-term,. maJonty show pathologies; a subdiaphragmatic collection on the right
improvement but nearly two-thirds of patients have some side may manifest as right shoulder pain and ureteric pain
form of constipation or continence problem. is referred to the corresponding side as testicular pain.
Radiation of pancreatic pain to the back and ureteric pain
Suggested Reading from loin to groin are also known.
• Benninga MA, Voskuijl WP, Tininiau JAJM. ,childh~od Physicians must distinguish abdominal pain due to
constipation: is there new light in the tunnel. J Pediatr
emergent diagnoses like appendicitis or intussusception
Gastroenterol Nutr 2004; 39:448-64.
• Tabbers MM, Di Lorenzo C, Berger MY. Evaluation a~d treatment from benign conditions like gastroenteritis or constipation.
of functional constipation in infants and children: evidence b~ed Examination should be meticulous including examination
recommendations from ESPGHAN and NASPGHAN. J Pediatr of genitalia as torsion of testes or incarcerated hernia can
Gastroentcrol Nutr 2014; 58:258-67. be easily overlooked. Differential dia?°osis should be
• Khanna V Poddar U, Yachha SK. Etiology and clinical spectrum considered in terms of age as many diagnoses are seen
of constip~tion in Indian children. Indian Pediatr 20~0; 47:1025-30.
• Langer JC. Hirschsprung disease. Curr Opin Pediatr. 2013 Jun; more commonly in children of certain age groups as
25(3):368-74. shown in Table 12.5.
- 2e2 I -------------~E!ss~e:!:n!!!tl~a~I~P!ed~l~a~tr~lc~s~-------------~ 1
Suprapublc
Acute appendicitis Colitis
Pelvic inflammatory disease Constipation
Tuberculosis abdomen Pelvic inflammatory
disease
Fig. 12.1 o: Causes of abdominal pain as per site of pain. RH right hypochondrlum; LH left hypochondrlum
Table 12.5: Common causes of abdominal pain distention and infection in the appendix causes
progressive inflammation and, subsequently, perforation.
Infants and young children (<2 years of age): Colic, ac~te
The patient presents with fever and anorexia followed
gastroenteritis, intussusception, malrota.tl?n of gut w.1t.h
volvulus, incarcerated hernia, trauma, necrot1z1ng enterocoht1s by pain in the periumbilical area. Vomiting follows the
periumbilical pain, unlike in gastroenteritis. As the
Preschool children (2-5 years of age): Acute gastroenteritis, inflammatory fluid spreads, the pain is then felt in ~e
urinary tract infections, constipation •. intussuscepti?n, a~ute right iliac fossa (McBumey point) towards which the child
appendicitis, malrotation of gut with volvulus, intestinal characteristically points with a finger . A retrocecal
perforation with peritonitis, choledochal cyst, lower lobe inflamed appendix may be difficult to diagnose and may
pneumonia, incarcerated hernia, torsion testis, acute
manifest as spasm at the hip. The diagnosis is most o~ten
pancreatitis, diabetic ketoacidosis, Henoch-Schonlein purpura,
based on clinical suspicion after history and examination.
Meckel diverticulum, trauma
Palpation reveals localized tenderness and is best elicited,
Older children and adolescents: Acute gastroenteritis, gastritis, if there is rebound tenderness.
acute appendicitis, Crohn disease, constipation, urinary tra~t Hemogram shows polymorphonuclear leukocytosis.
infections, dysmenorrhea, pelvic inflammatory disease, ectopic Urine microscopy should be done to rule out urinary tract
pregnancy, Mittelschmerz, renal calculi, acute pancreati~is, infection. Abdominal ultrasound detects a dilated (>6 aun)
cholecystitis, pneumonia, trauma, early phase of acute viral
tubular, aperistaltic structure which is not compressi~le
. hepatitis, testicular or ovarian torsion, intestinal obstruction,
perforation or peritonitis
and is surrounded by fluid. Ultrasound has a sensith'.1ty
of 85-90% and specificity of 95-100% for diagnosing
Acute Appendicitis appe~dicitis : Com~uted tomography may be don;
occas1onally, if the diagnosis is in doubt. In up to on
Acute appendicitis is the commonest pediatric surgical third of patient~, the appe~~ ruptures before s~rge~
emergency and is more common in older children. The Intravenous flwds and antibiotics for gram-negattve an
condition is considered as occurring due to obstruction anaerobic coverage should be given in all cases. Ea.rlY
of the appendiceal lumen by either fecolith or lymphoid surgery is necessary to prevent complications 111'e
tissue, e.g. following viral infection. The obstruction, perforation, appendiceal abscess and sepsis.
Diseases of Gastrointestinal System and Liver j 2aa •
tntussusceptlon investigation of choice for diagnosis of gallstones. MRCP
This is a common cause of intestinal obstruction in children and ERCP have a better accuracy than ultrasonography
between 3 months and 6 years. Intussusception refers to in diagnosing common bile duct stones. These children
the telescoping of a proximal segment of intestine should be investigated with hemoglobin, reticulocyte
(intussusceptum) into a distal segment (intussuscipiens). count, peripheral blood picture and other investigations
This may be ileocolic, colocolic or ileoileal. Most cases to look for hemolytic disease.
occur in infants during the weaning period following Ma11ageme11t: Symptomatic cholelithiasis is treated by
introduction of a new food, vaccination or upper open or laparoscopic cholecystectomy. Common bile duct
respiratory tract infection. An area of enlarged subrnucosal calculi can be removed by ERCP or at surgery by common
Peyer's patch probably acts as a lead point. Beyond two bile duct exploration. Children with asymptomatic gall-
years of age, the possibility of a subrnucosal lead point stones without underlying predisposing factors can be
like liporna and polyp that needs surgical resection should safely followed up. Patients with sickle cell disease s_hould
be considered as failure to resect them will lead to be subjected to prophylactic cholecystectomy, even 1f gaJ.1-
recurrence. Inflammatory conditions, like Henoch- stones are asymptomatic. Children with other hemolytic
Schonlein purpura, also result in intussusception. As a anemias should be screened by ultrasonography, if they
result, there is venous congestion, bowel edema leading are being considered for splenectomy and cholecystec-
to arterial obstruction, bowel ischemia, necrosis, tomy should be done along with splenectomy in those
perforation and shock. The classic triad of abdominal pain, having gallstones.
red currant jelly stools (blood and mucus) and palpable
mass is seen only in a small percentage of children. X-ray Chotedochal Cyst
abdomen shows paucity of air in right lower quadrant.
Choledochal cyst refers to abnormal cystic dilatation of
mtrasound is the investigation of choice that confirms the
biliary tree either as a single or multiple dilatations. This
diagnosis ('doughnut'sign) and provides information
may or may not have associated intrahepatic cystic
about presence of a mass as lead point. Vascularity of
dilatations. It can present in the neonatal period as
bowel is best assessed on color Doppler. Barium enema
cholestasis, mimicking biliary atresia (5% of all neonatal
shows a characteristic 'claw' sign, if the intussusception
cholestasis), or in the older child with recurrent episodes
involves colon. Early reduction either with saline (under
of pain, obstructive jaundice or mass in right upper
ultrasound guidance), barium contrast (both diagnostic
quadrant. Acute or recurrent pancreatitis may be the
and therapeutic) or with air insufflation is advisable.
presentation of choledochal cyst, either due to stone
Reduction with air is safer with lower recurrence rates.
impaction at lower end of common bile duct, or due to
Failure of radiological reduction or suspected intestinal
anomalous pancreatobiliary junction known to be
gangrene may necessitate surgery and resection. associated with choledochal cyst. Biliary peritonitis
secondary to bile duct perforation can complicate a
Gallstones (Cholelithlasls}
choledochal cyst. Untreated cases may go on to develop
I
Gallstones are of three main types: Cholesterol stones with secondary biliary cirrhosis.
>50% cholesterol, pigment (black or bro~) ~tones ~d Ultrasonography is the investigation of choice to
mixed types. Pigment stones are common m childr~n with
diagnose choledochal cyst. MRCP is done to define the
hemolytic anemia. High-risk groups for.gall~tones mcl~de anatomy of the pancreaticobiliary ductal system before
children with hemolytic anemia, obesity, 1leal resec~on surgical excision (Fig. 12.11). Definitive treatment is with
or disease, intake of drugs like ceftriaxone, progressive cyst resection and hepaticojejunostomy in the majority as
familial intrahepatic cholestasis ~ype II~ and total there is a risk of malignancy (cholangiocarcinoma) in the
parenteral nutrition Overall, hemolytic anemia and other epithelium of the cyst, if left i11 situ. Antibiotics and
predisposing conditlons account for 20-30% and 30-40~/o supportive therapy are required before surgery for a child
of gallstones, respectively, while 30-40% cases remain presenting with obstructive jaundice and cholangitis.
idiopathic.
Clinical presentation: Typical presentation is wi~ acu~e Matro tat/on
or recurrent episodes of right upper quadrant or ep1gastric Rotational abnormalities developing during the matura-
P~ Which may radiate to the right sho~lder. kterus a~d tion of the gut cause recurrent obstruction, occurring as
Pain radiating to the back is suggestive of a. ~tone m either the Ladd's band or volvulus of the gut over the
~0nunon bile duct or ampulla causing pancreahtis. Fever narrow mesenteric pedicle. About 80-90% cases of
is uncommon; however, if present, it suggests presence volvulus occur within the first year of life. Abdominal pain
of cholecystitis or cholangitis. with bilious vomiting suggests small bow~l obstr_uc~on;
Diagnosis: Serum bilirubin and alkaline phosphatase_ are abdominal distension may not be a prominent fmdmg.
elevated, if the stone is in the common bile duct. ~aised Findings of malrotation are confirmed on bari~ _meal
a.rnylase suggests pancreatitis. Ultrasonography is the follow through (BMFT), which shows duoden0Je1unal
- 284 j
Fig. 12.11: Magnetic resonance cholanglopancreatography Fig. 12.12: Barium meal follow through showing ma!rotot'ai d
(MRCP) showing choledochal cyst Intestine
junction on the right of the spine (rather than to the left of antral nodularity as compared to ulcers without such
midline at the level of pylorus), an abnormally positioned infection. Mechanical ventilation and coagulopathy
caecum and small bowe l loops on the right side of increase risk of bleeding in stress ulcers.
abdomen (Fig. 12.12). If volvulus is also present, the Diagnosis is established by upper GI endoscopy by
contrast abruptly tapers into a corkscrew appearance at direct visualization of location (gastric or duodenal),
the level of the second portion of duodenum. number and size of ulcer (Fig. 12.13). Endoscopic
After resuscitation, emergency laparotomy is required management can be done at the same time in ulcers with
for correction of the defect, u sually by the Ladd's active bleeding or ooze or those with a visible \'essel. One
procedure, which includes derotation of the volvulus, can also obtain gastric biopsies for HelicoLiacter pylori
division of the Ladd's band, widening of the base of the testing.
mesentery, placement of bowel in a state of nonrotation Proton pump inhibitors are the mainstay of therapy.
and appendicectomy. Actively bleeding ulcers require endoscopic therapy, \1~th
sclerosant or adrenaline injection, application of heater
Peptic Ulcer probe or bipolar electrocoagulation, or placement of
Both gastric and duodenal ulcers occur infrequently in hemoclip over bleeding vessel. Evaluation fo r Helicobadrr
children. Ulcers may be primary, i.e. related to Helicobacter
pylori or secondary, e.g. due to drugs (NSAIDs, steroids),
stress (shock, sepsis and ischemia), corrosives, Menetrier' s
disease, Crohn's disease and Zollinger-Ellison syndrome.
Clinical presentation depends on the age. Neonates
typically present with bleeding and perforation from a
gastric ulcer, usually occurring in the setting of another
underlying problem, such as sepsis or respiratory distress.
Older infants and toddlers frequently vomit, eat poorly
and have upper GI bleeding. Older children may have
the classical epigastric pain which is relieved by eating.
However, this is noted only in a minority; most patients
have pain that is ill-localized and similar to that seen in
functional dyspepsia. Overt or occult bleeding is seen in
approximately half of school-age children -~ith ul~er
disease . Gastrointestinal bleeding, v omiting with
obstruction and severe pain due to perforation _suggest
complicated ulcers. Ulcers associated with Helzcobacter
pylori infection affect older children, family history of ulcer Fl 1 h0wll'l9
d g. 2 -13: Upper gastrointestinal endoscoPY 5
disease is usually noted and upper GI endoscopy shows UOdenal ulcer in the first part of duOdenurn
Diseases of Gastrointestinal System and Liver j2es -
pylori is essential~ all cases with pe~ti.c ~leer and ~~r~ts an important cause is nonorganic abdominal pain which
specific therapy with two of three antibiotics (amox1c1lhn, is responsible for nearly 75% of all cases. As per the Rome
metronidazole, clarithromycin) and proton pump III criteria, such pain is termed 'abdominal pain related to
jnhibitor. Predisposing factors, including NSAIDs, should functional gastrointestinal disorders.'
be avoided. Surgery is indicated in children presenting
with gastric outlet obstruction or uncontrolled bleeding Chronic Pancreatltls
despite drug and endoscopic treatment. This condition is characterized by recurrent episodes of
abdominal pain and exocrine and/ or endocrine pancreatic
Acute Pancreatitis insufficiency. On imaging, diagnosis is based on demonstra-
Acute pancreatitis is less common in children than adults tion of pancreatic calcification and/or dilated pancreatic
and occurs chiefly due to trauma, drugs (valproate, L- duct. Chronic pancreatitis in children may be idiopathic
asparaginase), viral infections (mumps), hemolytic uremic or hereditary, autoimmune, tropical, metabolic (hyper-
syndrome, congenital biliary anomalies, Henoch- calcemia) or secondary to recurrent acute pancreatitis.
Schonlein purpura and occasionally, gallstones, Children present initially with repeated episodes of
hypercalcemia or hypertriglyceridemia. Diagnosis is based pancreatic pain. Chronic diarrhea with fat malabsorption
on presence of upper abdominal pain (with or without (exocrine insufficiency) and symptoms of diabetes mellitus
radiation to the back), elevated serum amylase or lipase develop later along with failure to thrive. Local
and radiological imaging (ultrasonography, CT scan) complications include pseudocyst, pancreatic ascites,
showing bulky, edematous pancreas. Acute severe pancreatic duct stricture, biliary strictures and portal
pancreatitis may result in acute respiratory distress hypertension due to splenic vein thrombosis. These
syndrome, acute renal failure, shock, GI bleed, patients are also at an increased risk of pancreatic
disseminated intravascular coagulation, hypoglycemia, carcinoma, particularly those with hereditary pancreatitis.
hypocalcernia or infected pancreatic necrosis. Late X-ray abdomen may show pancreatic calcification.
complications include pancreatic abscess and pseudocyst Ultrasound and CT scan demonstrates ductal dilatation
formation (Fig. 12.14). Early supportive care in intensive (Fig. 12.15), strictures, calcification and altered size or
care is critical in severe acute pancreatitis. Radiological, echotexture of pancreas. ERCP and MRCP help define the
endoscopic or surgical interventions may be required for pancreatic ductal anatomy (e.g. prominent stricture,
patients with pseudocyst, pancreatic abscess or infected intraductal calculi) and planning of endoscopic or surgical
necrosis. therapy. Exocrine pancreatic insufficiency is confirmed by
demonstrating excess fat and reduced pancreatic elastase
Chronic Abdominal Pain or chyrnotrypsin in stool. Fasting and postprandial blood
Chronic abdominal pain refers to the pain that is either sugar help evaluate for endocrine insufficiency. Evalua-
episodic or continuous and lasts for a period of at least tion for etiology should include looking for hypercalcemia
2 months. The prevalence of chronic abdominal pain in or hyperlipidemia and testing for mutations in cationic
children varies from 0.5 to 19% and depends on the age trypsinogen gene to confirm hereditary pancreatitis.
group evaluated. The principles of diagnosis with regard Treatment includes supportive therapy during acute
to clinical evaluation are similar to that in acute abdominal attacks, administration of antioxidants and oral pancreatic
•
pain but the etiologies differ. In addition to organic causes, enzyme supplements for exocrine pancreatic insufficiency
~lg. 12.14: Contrast-enhanced CT scan showing pseudocyst Fig. 12.15: CT scan showing dilated main pancreatic duct In
n a Patient with acute pancreatltls chronic pancreatltls
".
- 286 I Easentlol Padlotrlca
- ~
and endoscopic, rndiologicnl or surgical lrcnlmcnt for ;Table 12.8: 'Red flag' signs or features that Indicate serioos
pseudocyst, ductal stricture nnd other complicntio nr-1. lllnosss In a chlld with abdomlnal pain
Surgical procedures like partinl pnncrL•nlcctomy or lntcral Pain locallzed away from umblllcus In right/left upper or lower
pancreatojejunostomy nrc required in patil•nts not quadrant
responding to medical thl.'rnpy. Celine gnnglion block is Nocturnal pain
another nlterm\tivc for pain control. Mnn•lgcmcnt of Fnllura to thrive; weight loss
diabetes mellitus, if present, is csscnlinl. Significant vomiting; billous vomiting
Gastrolnlestlnal blood loss
Abdominal Pain Related to Functional Chronic diarrhea
Gastrointestinal Disorders Perslslent fever
Abdominal pain related to functional GI disorders is Jaundice
diagnosed in the presence of p ain lhat is present at least Arthrllls; rash
once a week in the preceding 2 months and the absence of Family history of Inflammatory bowel disease
an organic cause such as an inflammatory, anatomic, Localized tenderness or mass In abdomen; organomegaly
metabolic and neoplastic process. The pain is typically Perianal fistulae
periumbilical and is clearly localized by the child.
Among the various types mentioned above, functional
After extensive studies, the most accepted under-
abdominal pain is the most common. The diagnosis of
standing of childhood functional abdominal pain is of childhood functional abdominal pain h inges on
'visceral hyperalgesia', referring to an altered excessive confidently ruling out organic etiology using a careful
perception of normal gut motility that is interpreted by history and examination; extensive in vestigations are
the child as pain. This perception is influenced by the unnecessary. The history should include not only details
psychosocial stressors in school and home. The focus on of pain but a lso family details, child ' s emotional
the pain is further heightened by the growing concern in environment in home and school, personality, coping
the family and the frequent visits to the doctors. Children skills, school performance and stress factors. The presence
of parents with increased anxiety and functional GI of alarming symptoms (Table 12. 6) inc reases the
problems have an increased risk of developing functional probability of organic disorder and jus tifies fu rther
pain in abdomen. The different types of functional gastro- diagnostic testing. In the absence of red flags. the
intestinal disorders associated with abdominal pain are diagnostic yield of investigations is poor. Hemogram, ESR.
as follows: stool routine and occult blood, and u rin e micrcscopy
F1111ctio11al dyspepsia: Persistent or recurrent pain or should be carried out in all cases to rule out o:"'anic
discomfort is centered in the upper abdomen, located disease. Abdominal ultrasonography is not he!~1ful; the
above the umbilicus and not relieved by defecation nor presence of lymph nodes of <10 mm is not a si.;:cticant
associated with a change in stool frequency or form (i.e. finding. Further investigation is required only ... those
no irritable bowel syndrome). w ith alarm symptoms and b ased on the likely c1~~-n~is.
The aim of management of children \•.rith iun~tionJl
Irritable bowel syndrome: Abdominal discomfort or pain abdominal pain is to make a positive d iagnosis, 1~ r!T'.J.lizi?
is associated with two or more of the following: the lifestyle to not allow pain to curtail d.Uly acfr. Ji~ or
improvement with defecation, onset associated with a school performance, and to recti fy psychological £,1 tors.
change in frequency of stool and onset associated with a The crux of management is counseling the parct~l5 ;md
change in consistency of stool. the child, both jointly and separately. Parents nl'-:.'\.i to be
Abdominal migraine: Paroxysmal episodes of intense, reassured about the benign nature of the ailmc·nt Jnd
acute periumbilical pain are noted, lasting for an hour or emphasis is laid upon avoiding too much attenti >:1 to the
more with intervening periods of normal health lasting child. The concept of visceral hyperalgesia sh0uld ?e
weeks to months. The episodes of pain interfere with explained to parents. Provision of a nutritious diet \\1 th
normal activities and are associated with two or more of adequate fiber and avoiding inta ke of carbona.ted
the following: Anorexia, nausea, vomiting, h eadache, bcvcrnges and refined food helps in reducing blo,1.tmg.
photophobia and pallor. The role of amitriptylinc and h ypnotherapy is rcstncted
to a few refractory cases.
C11ildl10od f1111ctio11al abdomi11a/ pain:This refers to episodic
or continuous periumbilical abdominal pain that meets Suggested Reading
insufficient criteria for other types of FGIDs (functional • a.11d
• Chiou E, Nurko S. Milnugcmcnt of functional abdominal pJ.lfl R v
gastrointestinal disorders). The criteria for childhood Irritable bowd syndrome in children and adolescents. Expert e
functional abdominal pain syndrome are satisfied, if the child Gastrocntl'rol Hl•p•l lol 2010; 4:293-304. . a
has functional abdominal pain for at least 25% of the time • Korterink J, Dcvanarnyana NM, Rajindrajith S, Vlieger A'.BenJUllSd
plus ?n~ or more of the following: Some loss of daily MA. Childhood functional abdominal pain: mechan 1 srn;: ;
1.
management. Nat Rev Gastroenterol Hcpatol. 2015; 12(3):1' CJill
functiorun~ and additional somatic symptoms such as • Marin JR, Alpern ER. Abdominal pain in children. Ernerg Med
headache, limb pain, or difficulty in sleeping. North Am 2011; 29:401-28.
Diseases of Gastrointestinal System and Liver 287 -
~.ACUTE DIARRHEA Table f2.7: Causes ofacute diarrhea
I
rapid (Kussmaul breathing). deficiency), systemic infection (presence of cough, high
Clinical features can be summed up as follows. The grade fever, fast breathing and/ or chest ind rawing
child is thirsty and slightly irritable in early and mild cases suggests pneumonia; high grade fever with splenomegaly
of diarrhea. As the diarrhea continues and dehydration suggests malaria) and fungal infections (oral thrush or
worsens, the child becomes more irritable and develops a perianal satellite lesions).
pinched look. The fontanelle, if open, is depressed, the
eyes appear sunken and the tongue and the inner side of Laboratory investigations: The large majority of acu~e
cheeks appear dry. Abdomen may become distended in diarrheal episodes can be managed effectively even~
hypokalemia. The child passes urine at longer intervals. absence of laboratory investigations. Stool microscoPY 15
As acidosis worsens, the breathing becomes deep and not helpful in management except in selected situations,
rapid. In extreme cases, the child appears moribund, with such as cholera (darting motion suggests Vibrio cholerae)
weak and thready pulses, low blood pressure and reduced and giardiasis (trophozoites). Stool culture is of little value
urine output. Children with severe dehydration may in routine management of acute diarrhea. It is useful to
succumb rapidly, if not treated promptly. decide on antibiotic therapy in patients with Sllig~l~a
dysentery who do not respond to the initial empiric
Assessment of Child with Acute Diarrhea antibiotics. Tests for stool pH and reducing substallces
are not indicated in acute diarrhea. Hemograrn, blood ga~
Goa~s of asse~sment: These are to: (i) determine the type
of d~arrhea, 1.e. acute watery diarrhea, dysentery or ~s~ation, serum electrolytes, renal function tests are;d
md1cated routinely and are performed, only if the c.
persIStent diarrhea; (ii) look for dehydration and other
has associated findings like pallor, labored breathillg'
Diseases of Gastrointestinal System and Liver I 2a9 -
unconsciousness.
2
1n some infants and children, the eyes normally appear somewhat sunken. It is helpful to ask the mother, if the child's eyes are normal or more
sunken than usual.
3Dryness of the mouth and tongue can also be palpated with a clean finger. The mouth may be dry in a child who habitually breathes through
the mouth. The mouth may be wet in a dehydrated child owing to recent vomiting or drinking.
4The skin pinch is less useful in infants or children with marasmus (severe wasting), kwashiorkor (severe malnutrition with edema) and in
obese children.
altered sensorium, seizures, paralytic ileus or oliguria concentration gradient, which also results in electrolyte
which suggests acid-base imbalance, dyselectrolytemia or absorption (by solvent drag). Since the concentration of
renal failure. glucose increases osmolarity, it is suggested that glucose
concentration should not exceed 111 mmol/L. Meta-
Principles of Management analyses have shown that use of low osmolarity ORS
Management of acute diarrhea has four major causes reduction of stool output, decrease in vomiting and
components: (i) rehydration and maintaining hydration; decrease in the use of unscheduled intravenous fluids
(ii) ensuring adequate feeding; (iii) oral supplementation without increasing the risk of hyponatremia. For this
of zinc; and (iv) early recognition of danger signs and reason, the recommendation for use of standard WHO
treatment of complications. ORS (having osmolarity of 311 mmol/L) was changed to
The cornerstone of acute diarrhea management is low osmolarity WHO ORS (having osmolarity of
rehydration by using oral rehydration solutions. After the
history and examination, the child's dehydration status
is classified as no dehydration, some dehydration or severe
dehydration and appropriate treatment is started.
245 mmol/L). Since 2004, based on the WHO / Ul\.TICEF
and IAP recommendations, the Government of India has
adopted the low osmolarity ORS as the single universal ORS
to be used for all ages and all types of diarrhea. The com-
position of the low osmolarity ORS is given in Table 12.9.
lfJ
Pliysiological basis for oral rehydration therapy: In most In the absence of WHO ORS, one may administer
cases of acute diarrhea, sodium and chloride are actively culturally acceptable appropriate homem~de fluids as
secreted from the gut mucosa due to pathogen-induced shown in Table 12.10. Oral solutions should be given by a
dysfunction of several actively functioning absorption spoon or katori and in sips or small volumes rather than a
pumps. However, glucose dependent sodium pump large volume at one time as this increases the retention of
remains intact and functional transporting one molecule oral fluids.
of glucose and dragging along a molecule .of s?dium ":11d
one of water across intestinal mucosa resulting in repletion Table 12.9: Composition of WHO recomm~nded ORS
of sodium and water losses. The glucose dependent Constituent g/L Osmofe or ion mmoVL
sodium and water absorption is the principl~ b~hind
Sodium chloride 2.6 Sodium 75
replacing glucose and sodium in 1:1 molar r~ho m the
WHO oral rehydration solution (ORS). An imp~rtant Glucose, anhydrous 13.5 Chloride 65
consideration in making ORT is that the osmolanty of Potassium chloride 1.5 Glucose, anhydrous 75
the replacement fluid should not exceed that of blood Trisodium citrate, 2.9 Potassium 20
(290 mmol/L). Keeping the intestinal lumen at lower dihydrate Citrate 10
0 smolarity as compared to blood allows for greater Total osmolarity 245
absorption of fluids into the bloodstream across
~ 290 I ~~~~~~~~~~~~~~E~s~s~e~n~tl~a~l~P~e~d~la~tr~lc~s=----~~~~~~~~~------
--.-----::.,..-~ -~~-- ~
Table 12.10: Home available flulds tor acute _diarrhea fTable 12.11: Oral rehydration therapy to prevent dehydrati0
Acceptable home available flulds (Plan. A) 11
Age ORS or other culturally ORS to provide fo
Fluids that contain salt Oral rehydration solution, appropriate ORT fluids use at home r
(preferable) salted drinks (e.g. salted rice after each loose stoo,I
water or salted yoghurt drink),
vegetable or chicken soup <24mo 50-100 ml 500 mUday
with salt 2-10 yr 100-200 ml 1000 mUday
Fluids that do not contain Plain water, water in which a >10 yr Ad lib 2000 mUday
salt (acceptable) cereal has been cooked (e.g. Explain use of OAS, i.e. the amount to be given, how to mix
unsalted rice water), unsalted Give a teaspoonful every 1-2 min for a child under 2 years
soup, yoghurt drinks without Give frequent sips from a cup for an older child
salt, green coconut water, If the child vomits, wait for 10 min. Then give the solution more slowl
weak unsweetened tea, (for example, a spoonful every 2-3 min) Y
unsweetened fresh fruit juice If diarrhea continues after the ORS packets are used up, tell the mothe
to give other fluids as described above or return for more ORS r
Unsuitable home available Commercial carbonated
fluids beverages, commercial fruit
juices, sweetened tea ii. Deficit replacement or rehydration therapy is calculated
as 75 mL/kg of ORS, to be given over 4 hours. If ORS
Treatment Plan A: Treatment of "No DehydrationH cannot be taken orally, then nasogastric tube can be
used. If child's weight cannot be taken, then only age
Such children may be treated at home after explanation
may be used to calculate fluid requirement as shown
of feeding and the danger signs to the mother/ caregiver.
in Table 12.12.
The mother may be given WHO ORS for use at home as
per Table 12.11. Danger signs requiring medical attention If, after 4 hours, the child still has some dehydration,
are those of continuing diarrhea beyond 3 days, increased then another treatment with ORS (as in rehydration
volume/frequency of stools, repeated vomiting, therapy) is to be given. This therapy is effective in 95%
increasing thirst, refusal to feed, fever or blood in stools. cases. Oral rehydration therapy may be ineffective
in children with a high stool purge rate of >5 mL/kg
Treatment Plan B: Treatment of MSome Dehydration" body weight/hr, persistent vomiting >3/hr, paralytic
All cases with obvious signs of dehydration need to be ileus and incorrect preparation of ORS (very dilute
treated in a health center or hospital. However, oral fluid solution).
therapy must be commenced promptly and continued iii. Maintenance fluid therapy to replace losses. This phase
during transport. Fluid requirement is calculated under should begin when signs of dehydration dis;;ppear,
the following three headings: (i) provision of normal daily usually within 4 hours. ORS should be administered
fluid requirements; (ii) rehydration to correct the existing in volumes equal to diarrheal losses, usually to a
water or electrolyte deficits; and (iii) maintenance to replace maximum of 10 mL/kg per stool. Breastfeed ing and
ongoing losses to prevent recurrence of dehydration. semisolid food are continued after replacement of
i. The daily fluid requirements in children are calculated deficit. Plain water can be offered in between.
as follows:
Treatment Plan C: Children with "Severe Dehydration·
Up to 10 kg = 100 mL/kg
10-20 kg = 50 mL/kg Intravenous fluids should be started immediately using
>20 kg = 20 mL/kg Ringer lactate with 5% dextrose. Normal saline or plain
As an example, the daily fluid requirement in a child Ringer solution may be used as an alternative, but 5%
weighing 15 kg will be 1250 mL (first 10 kg, 10 x 100 dextrose alone is not effective. A total of 100 mL/kg of
fluid is given, over 6 hours in children <12 months and
= 1000 mL; another 5 kg, 5 x 50 =250 mL, total 1000 + over 3 hours in children >12 months as shown below.
250 =1250 mL).
Lactobac1
•11 GG) L. plantarum, several strains
fiaec1um
. SF68 and the y1 o. ~d
agents, necrotizing enterocolitis or septicemia. ~ these . usEnterococcus
'
cases, oral intake should be withheld. Hypokale~a along bacteria, .. b h east
boulard11 have een s own to have 50
with paralytic ileus necessitates intravenous fluids and SaccharomYces d t' f . me
. . reducing the ura ion o acute diarrhea .
nasogastric aspiration. Potassium chloride (~D-40 mEq/L) efficacy in f ·11
d . very early phase o i ness.
Th r1f
e efficacy f
should be administered intravenously with parenteral starbt~ ti' mpreparations is strain and concentration (doc~)
fluids provided the child is passing urine. pro io c · f b' · · ""'
s ecific. However, the routine use o pro iotics m patients
Convulsions associated with diarrhea may be due Jith acute diarrhea is not recommended.
to (i) hypo- or hypernatremia; (ii) hypoglycemia;
(iii) hypokalemia following bicarbon~t.e the~apy f_or Prevention of Diarrhea and Malnutrition
acidosis; (iv) encephalitis; (v) meningitis; ~vi) fe~nle
seizures; or (vii) cerebral venous or sag1tt~l smus Prevention of diarrhea and its nutritional consequences
h . . h 1h d
thrombosis. The management depends on the etiology. h0 uld receive major emp as1s m ea t e ucation. The
sthree main measures to ach'ieve this are:
Drug Therapy i. Proper nutrition: Sin~e breast milk offers distinct
Most episodes of diarrhea are self-limiting a~d d~ not advantages in promo~g growth ~d devel~pment of
require any drug therapy except in a few situations. the infant and protection from diarrheal illness, its
Antibiotics are not recommended for routine treatment continuation should be encouraged. Exclusive breast-
of acute diarrhea in children. In acute diarrhea, feeding may not be adequate to sustain growth beyond
antimicrobials are indicated in bacillary dysentery, cholera, the first 6 months of life. Therefore, supplementary
amebiasis and giardiasis. Escherichia coli are normal gut feeding with energy-rich food mixtures containing
flora and their growth on stool culture is not an indication adequate amounts of nutrients should be introduced
for antibiotics. Acute diarrhea may be the manifestation by 6 months of age without stopping breastfeeding.
of systemic infection and malnourished, prematurely born ii. Adequate sanitation: Improvement of environment
and young infants are at a high risk. Thus such babies sanitation, clean water supply, adequate sewage
should be screened and given adequate days of age disposal system and protection of food from exposure
appropriate systemic antibiotics for sepsis. Presence of to bacterial contamination are effective long-term
(i) poor sucking; (ii) abdominal distension; (iii) fever or strategies for control of all infectious illnesses including
hypothermia; (iv) fast breathing; and (v) significant diarrhea. Three 'Cs; clean hands, clean container and
lethargy or inactivity in well-nourished, well-hydrated
clean environment are the key messages. Mother
infants points towards sepsis.
should be properly educated about this. Complemen-
There is little scientific evidence that binding agents tary foods should be protected from contamination
based on pectin, kaolin or bismuth salts are useful. Their during preparation, storage, and at the time of
use is not recommended in acute diarrhea. Antimotility administration.
agents such as synthetic analogues of opiates (diphenoxylate
hydrochloride or lomotil and loperamide or imodium) iii. Vaccination: Evidence suggests that with improvement
reduce peristalsis or gut motility and should not be used in sanitation and hygiene in developing countries, the
in children with acute diarrhea. Reduction of gut motility burden of bacterial and parasitic infectio n has
allows more time for the harmful bacteria to multiply. decreased and viral agents have ass umed. an
These drugs may cause distension of abdomen, paralytic increasingly important etiologic role. Effective vacc~es
ileus, bacterial overgrowth and sepsis and can be are now available against the commonest agent, i.e.
dangerous, even fatal, in infants. rotavirus and their use might be an effective strategy
for preventing acute diarrhea.
AntisecretonJ agents have been used in acute diarrhea.
Racecadotril is an antisecretory drug that exerts its Suggested Reading
antidiarrheal effects by inhibiting intestinal enkephalinase. • Bhatnagar S, Lodha R, Choudhury P, Sachdev HPS, Shah N,
Recent studies reported some evidence in favour of Narayan S, et al. IAP Guidelines 2006 on management of acute
racecadotril over placebo or no intervention in reducing diarrhea. Indian Pediatr 2007; 44:380. 'cl .
the stool output and duration of diarrhea in children with • Piececik-lech M, Shamir R, Guarino A, Szajewska H. Revie\" ~rti e;
acute diarrhea. However, more data on efficacy is needed the management of acute gastroenteritis in children. Alune!l
Pharmacol Tuer. 2013; 37(3):289-303.
before it can be recommended for routine use in all
children with acute diarrhea.
Dysentery
Probiotics, defined as microorganisms that exert beneficial Dysentery refers to the presence of grossly VlSI· 'ble bloodn
effects on human health when they colonize the bowel, in the stools and is a consequence of infection of the co1~
have been proposed as adjunctive therapy in the treatment
of acute diarrhea. Several microorganisms like Lactobacillus
by either bacteria or ameba. Bacillary dysentery is
more common in children than amebic dysentery. ·es
m;e
rhamnosus (formerly Lactobacillus casei strain GG or bacteria causing bloody diarrhea are Sliigella speci
Diseases of Gastrointestinal System and Liver I 293 •
(S. dysenteriae, S. flexneri, S. boydii and S. sonnei.), entero- the gut. Th.is worsens nutrient absorption and initiates
invasive and enterohemorrhagic E. coli, Salmonella and a vicious cycle that can only be broken by proper
eampylobacter jejimi. S. flex11eri is the commonest organism nutrition. Persistent diarrhea is more common in
reported in ?eveloping countries and S. dyseriteriae is malnourished children. Apart from malabsorption,
associated with epidemics of dysentery. malnutrition also results from inadequate calorie
A child with bacillary dysentery presents with fever intake due to anorexia, faulty feeding and improper
and diarrhea. Diarrhea may be watery to start with, but counseling regarding feeding by doctors. One of the
then shows mucus and blood mixed with stools. There is major obstacles to nutritional recovery is secondary
tenesmus, which refers to ineffectual defecation along with lactose intolerance, and in some cases, impaired
str~g and suprapubi~ discomfort. The illness may be digestion of other complex carbohydrates due to
comp.licated by dehydratio_n, dyselectrolytemia, hemolytic decrease in brush border disaccharidases.
uremtc syndrome, convulsions, toxic megacolon, intestinal ii. Pathogenic E.coli, especially the enteroaggregative and
perforation, rectal prolapse and, very rarely, Shigella enteroadherent types, result in malabsorption by
encephalopathy. causing persistent infection.
Administration of ORS, continuation of oral diet, zinc iii. Associated infections of the urinary tract or another
supplementation and antibiotics are the components of focus of infection (more commonly in malnourished
treatment. Stool culture and sensitivity should be sent children) contribute to failure to thrive and mortality.
before starting empirical antibiotics. Antimicrobial agents
iv. Prolongation of an acute diarrhea may rarely be a
are the mainstay of therapy of all cases of shigellosis. Based
manifestation of cow milk protein allergy. The
on safety, low cost and efficacy, ciprofloxacin (15 mg/kg/ increased gut permeability in diarrhea predisposes to
day in two divided doses for 3 days) has been
sensitization to oral food antigens.
recommended by World Health Organization (WHO) as
the first line antibiotic for shigellosis. However, v. The use of antibiotics in acute diarrhea suppresses
normal gut flora. This may result in bacterial over-
antimicrobial resistance to fluoroquinolones had increased
significantly from 2002 to 2011 and only ceftriaxone has growth with pathogenic bacteria and/ or overgrowth
been shown to be uniformly effective. Keeping this in mind, of fungi, resulting in persistent diarrhea and
malabsorption.
intravenous ceftriaxone (50-100 mg/kg/ day for
~5 days) should be the first line of treatment in a sick child. vi. Cryptosporidizmz infection is frequently implicated in
In a stable child, either ciprofloxacin or oral cefixime may persistent diarrhea, even in immunocompetent
be given, but the patient should be monitored for clinical children.
improvement within 48 hours (decrease in fever, stool
frequency and blood in stools). If no improvement is seen Clinical Features
at 48 hours, antibiotics should be changed appropriately. Majority of patients with persistent diarrhea pass several
Oral azithromycin (10 mg/kg/ day for 3 days) can be used loose stools daily but remain well hydrated. Dehydration
for shigellosis but the experience is limited.
· Amebic dysentery is less common among children. The
onset is insidious. Tinidazole or metronidazole is the drug
of choice. Any young child presenting with blood in stools
and persistent abdominal pain should be suspected to
develops only in some patients due to high stool output
or when oral intake is reduced due to associated systemic
infections. The major consequences of persistent diarrhea
are growth faltering, worsening malnutrition and death
due to diarrheal or nondiarrheal illness. The presence of
I
have intussusception and evaluated accordingly. secondary lactose intolerance should be considered ·when
the stools are explosive (i.e. mixed with gas and passed
with noise) and in presence of perianal excoriation. The
PERSISTENT DIARRHEA
stool pH is low and stool test for reducing substances is
Persistent diarrhea is an episode of diarrhea, of presumed positive. Unabsorbed dietary lactose once delivered to
infectious etiology, which starts acutely but lasts for mo~e colon is converted to hydrogen and lactic acid by colonic
than 14 days. It should not be confused wit~ c~r?mc bacteria. Lactic acid results in decreased stool pH, explosive
diarrhea which has a prolonged duration but an ms~d10us stools are due to hydrogen and unabsorbed lactose gives
onset and includes conditions causing malabsorphon. positive reducing substances. There is no need for
laboratory testing for stool pH and reducing substances
Etlopathogenesls when the history is classical and excoriation is marked .
.t\_lthough persistent diarrhea starts as a~ute infec~ious
diarrhea, the prolongation of diarrhea is_not_ entlre~y Management
due to infection. Various factors that are implicated m The principles of management are: (i) correction of de-
Pathogenesis include: hydration, electrolytes and hypoglycemia; (ii) evaluation
i. The predominant problem is the worseru:'g nutrition~! for infections using appropriate investigations (hemogram,
status that, in tum, impairs the reparative process m blood culture and urine culture) and their management;
- 294 Essentlal Pediatrics
and (iii) nutritional therapy. Two-thirds of patients with cereal mixtures, e.g. m1"lk or curd rruxe
" d·nee gruel . ~
persistent diarrhea can be treated on outpatient basis. sooji gruel, or dalia ar~ palata~le, provide good q~~
Patients in need of hospital admission are those with roteins and some m1cronutnents and result in f ty
P . d. aster
(i) age less than 4 months and not breastfed; (ii) presence weight gain than nulk-free iets.
of dehydration; (iii) severe malnutrition (weight for height Secoud diet B (lactose-free dietwitli reduced starcli): Ab
<3 SD, mid-upper arm circumference <11.5 cm for children 65-70% of ch1l' d rei: 1mp_
.
r ove o~ th e. m1tia
. . . 1 d iet A. The
Out
at 6-60 months of age, or bilateral pedal edema); or remainder have impaired digestion of starch a d
(iv) presence or suspicion of systemic infection. disaccharides ~ther than l~ctose._These c~l~ren, if free:f
systemic infection, are advised diet B which is free of rnilk
Nutrition (lactose) and provides carbohydrates as a mixture of
Feeding should be started at the earliest. Initially 6-7 feeds cereals and glucose. Milk protein is replaced by chicken
are given everyday and a total daily caloric intake of egg or protein hydrolysate. The starch content is reduced
100 kcal/kg/ day is ensured. Caloric intake should be and partially substituted by glucose. Substituting only Part
increased gradually over 1-2 weeks to 150 kcal/kg/day of the cereal with glucose increases the digestibility but at
in order to achieve weight gain. Tube (nasogastric) feeding the same time does not cause a very high osmolarity.
may be done initially in children with poor appetite due Third diet C (monosaccharide-based di et): Overall
to presence of serious infection. To ensure absorption and
80-85% of patients with severe persistent diarrhea will
decrease stool output, one may attempt to overcome
recover with sustained weight gain on the initial diet A or
varying degrees of carbohydrate maldigestion by using
the second diet B. A small percentage may not tolerate a
diets with different degrees of carbohydrate exclusion in
moderate intake of the cereal in diet B. These children are
the form of diet A (lactose reduced), diet B (lactose free)
given diet C which contains only glucose and a protein
and dietC (complex carbohydrate free) diets (Table 12.13).
source as egg white or chicken or commercially available
Initial diet A (reduced lactose diet; milk rice gruel, milk protein hydrolysates. Energy density is increased by
sooji gmel, rice with curds, dalia): This is based on the adding oil to the diet.
fact that secondary lactose intolerance exists in children The strategy of serial carbohydrate exclusion to varying
with persistent diarrhea and malnutrition. Clinical trials degrees in plan A, B and C diets are meant to circumvent
have shown that reduced lactose diet is tolerated equally the problem of carbohydrate malabsorption. In addition
well as totally lactose-free diet, without significantly green (unripe) banana diet is gaining acceptance for
increasing stool output or risk of dehydration. If the treatment of persistent diarrhea. Fermentation of
patient is fed entirely on animal milk, the quantity should nondigestible soluble fibers in cooked green (unripe)
be reduced to 50-60 mL/kg providing not more than 2 g banana by colonic bacteria generates short chain fatty acids
of lactose/kg/ day. To reduce lactose concentration in which are absorbed along with sodium in the colon,
animal milk, it should be mixed with cereals, but not thereby facilitating water absorption by solvent drag and
diluted with water as that reduces the caloric content. Milk also conserving dietary nutrients.
II ~ -::~~reduced
Constituents
lactose)
Table ·12.1a:· Diets for persistent diarrhea ..
.
Diet B (lactose free)
-··--·-·- ·
Diet C (monosaccharide based)
-
Milk (1/3 katori/50 ml) Egg white (3 tsp/half egg white) Chicken puree (5 tsp/15 g) or
Puffed rice powder/cooked rice or Puffed rice powder/cooked rice egg white (3 tsp/half egg white)
sooji (2 tsp/6 g) (3 tsp/9 g)
Sugar (1 % tsp/7 g) Glucose (1 Y2 tsp/7 g) Glucose (1 Y2 tsp/7 g)
Oil (1 tsp/4.5 g) Oil (1% tsp/7 g) Oil (1 % tsp/7 g)
Water (2/3 katori/100 ml) Water (3/4 katori/120 ml) Water (1 katori/150 ml)
·~ Preparation
Mix milk, sugar and rice, add After whipping the egg white, Boil chicken and make puree after removing
· bones.
boiled water and mix well, add add rice, glucose and oil and mix Mix it with glucose and oil. Add boiled water to
oil. well. Add boiled water and mix make a smooth flowing feed
rapidly to avoid clumping
Nutrient content
85 kcal and 2.0 g protein 90 kcal and 2.4 g protein 67 kcal and 3.0 g protein per 100 g
per 100 g per100g
...
Diseases of Gastrointestinal System and Liver
I 295 -
f11dica!ions [or change from tlie initial diet (diet A) to the
11ext diet (diet B or diet C)' The di t h Id b h d st~ols/day.for 2 cons~cuti~e days) and weight gain. Most
the next level, if the child showse(.s) ou k de ~ ange ~o children will lose weight m the initial 1-2 days and then
1 mar e increase m
show steady weight gain as associated infections are
stool fre~uency (usually more than 10 watery stools/ day)
treated and diarrhea subsides. All children should be
at any time after at least 48 hours of initiating the diet·
followed regularly even after discharge to ensure conti-
(ii) featu~es o.~. de~ydration any time after initiatin~
treatment, or (m) failure to gain weight gain b d 7 . nued weight gain and compliance with feeding advice.
the absence of initial or hospital . dy ay ~ Prognosis
· Unl . acqmre systemic
infecti?n. ess si~ of treatment failure occur earlier,
each diet should be given for a minimum per10· d of 7 d ays. Most patients with persistent diarrhea recover with an
. approach of stepped up dietary management as discussed
R.es11mptto11 of regula~ diet after discharge: Children above. A small subgroup (<5%) may be refractory and
discharged on totally nulk-free diet should b · 11 require parenteral nutrition and extensive workup. These
.ti. f milk e given sma
quanti es o . as part of a mixed diet after 10 days. If patients generally have high purge rate, continue to lose
they tolerate
. this
. and have no signs of lactose m
· t o1erance weight, do not tolerate oral feeds and require referral to
(abdomma1 pam, . abdominal distens1'on and . exc~filve · specialized pediatric gastroenterology centers.
flatulence) then milk can be gradually increased over the
next few days. Age appropriate normal diet can then be CHRONIC DIARRHEA
resumed over the next few weeks. Chronic diarrhea is a common problem in children. It is
Supplement vitamins and minerals: Supplemental defined as an insidious onset diarrhea of >2 weeks
multivitamins and minerals, at about twice the RDA duration in children and >4 weeks in adults. The term
should be given daily to all children for at least 2-4 weeks: chronic diarrhea is not synonymous with persistent
Iron supplements should be introduced only after the diarrhea. The approach, etiology and management of
diarrhea has ceased. Vitamin A (as a single dose) and zinc chronic diarrhea along with a brief outline of some
are supplemented as both of them enhance the recovery common causes is discussed.
from persistent diarrhea. A single oral dose of vitamin A
Approach
should be given routinely, at 2,00,000 IU for children
>12 months or 100,000 IU for children 6-12 months. Approach to chronic diarrhea must be considered with
Children weighing less than 8 kg, irrespective of their age, the following points in mind:
should be given 1,00,000 IU of vitamin A. One should Age of onset: A list of common causes of chronic diarrhea
administer 10-20 mg per day of elemental zinc for at least according to age of onset is shown in Table 12.14.
2 weeks to children between 6 months and 3 years of age. Small or large bowel type of diarrhea: Features in history
Additio11al supplements for severely malnourislzed infants and examination that help in differentiating small bowel
and children: Magnesium and potassium supplementation from large bowel diarrhea is shown in Table 12.15.
is provided to these children. Magnesium is given by Typically, large volume diarrhea without blood and
intramuscular route at 0.2 mL/kg/ dose of 50% magnesium mucus suggests small bowel type of diarrhea and small
sulfate twice a day for 2-3 days . Potassium is volume stools with blood and mucus suggest large bowel
supplemented at 5-6 mEq/kg/day orall.Y: or .as par~ of type of diarrhea.
intravenous infusion during the initial stabilization penod. Gastrointestinal versus systemic causes: Diarrhea is most
Role of antibiotics: The indiscriminate use of antibiotics commonly of intestinal origin and sometimes pancreatic,
in the treatment of acute diarrhea is among the re~s?ns or rarely, hepatobiliary in etiology. Cholestasis due to
biliary obstruction or intrahepatic cause can cause diarrhea
for persistent diarrhea. Hence, t~e ~s~ of ~mpmcal
due to fat malabsorption. Pruritus and malabsorption of
antibiotics at admission is to be md1v1duahzed and
fat-soluble vitamins (A, D, E and K) and calcium are
reserved for children with either of the follow~g features:
commonly associated. Maldigestion due to deficiency of
(i) severe malnutrition (ma1·ority of these childr~n havef
pancreatic enzymes leads to pancreatic diarrhea in cystic
associated systemic infections an d c l imca' · 1 signs o.
fibrosis, Shwachman-Diamond syndrome (cyclic neutro-
infection may not be obvious); and (ii) evide~ce o~yst~truc penia and bone abnormalities) or chronic pancreatitis.
infection. A combination of cephalospormdanh amifnto- Other causes include Zollinger-Ellison syndrome, and
. · · lly an t erea er
glycoside can be started empmca I
t 5 of culture sens1
'ti"vi·ty
. secretory tumors like VIPoma, carcinoid or mastocytosis.
ch anged according to repor . l0-15%) and Diarrhea may also be a systemic manifestation of other
Urinary tract infection is common (seen in conditions like sepsis or collagen vascular disorders.
should be treated appropriately. Specific questions in history should include:
i. Duration of symptoms; nature, frequency and
Monitoring Response to Treatment consistency of stools; and presence of blood, mucus or
. d by adequate food
~itccessful treatment is charact~rJ.Ze stools (<2 liquid visible oil in stools
intake, reduced frequency of diarrhea1
- 296 ~----~~~~~~------~E~s~s~e~n~tl~a~l~P~ed~l~at~r~lc~s~--------------~~~~~---~
-· . •. . _ .- f onset -(in order of Importance)
Table 12.14: Causes of chronic diarrhea according to age o_ A e >5 years
Age >6 months to 5 years g
Age <6 months cellac disease
Cow milk protein allergy cow milk protein allergy Glardlasls
Lymphangiectasla Cellac disease
Gastrointestinal tuberculosis
Urinary tract Infection* Giard Iasis
Inflammatory bowel disease
Short bowel syndrome** Toddler diarrhea
lmmunodeffclency
Immunodeficiency states Lymphanglectasla
Bacterial overgrowth
Short bowel syndrome**
Cystic fibrosis Lymphangiectasia
Anatomical defects Tuberculosis
Tropical sprue
Intractable diarrheas of Infancy••• Inflammatory bowel disease
lmmunoprollferative small
Microvillous inclusion disease Immunodeficiency
Intestinal disease
Tufting enteropathy Bacterial overgrowth
Pancreatic insufficiency
Autoimmune enteropathy Pancreatic insufficiency
Glucose galactose malabsorption
Congenital sodium/chloride diarrhea
Should be considered in young infants with chronic diarrhea, particularly if fever is noted
•• Consider if there is antecedent history of small bowel surgery ..
These rare conditions should only be considered if the diarrhea is very early in its onset (neonate to 3 months) and common conditions have
been ruled out
l....--.. - - --.. _ , , _
Table 12.15: ·Differentiating-small bowel from large bowel diarrhea
I . Small bowel diarrhea Large bowel diarrhea
Features
Large Small
Stool volume
No Usually present
Blood in stool
Rectal symptoms, e.g. urgency, tenesmus No Yes
h
Dleeaaea of G111trolnt11tln'9I 8_Y.~•,::.;;
to;.:.:m.:...;;;;
on~d--
Ll_v_
or......._,_-=-,,_o;;;-=o..........---...
fibi81ill: Diagnostic clues to Important oauaol of chronlo r111111111m c1wtto of d 1ronlr dlftrfl 1,J11Int I11fd r' •ll t1vt! r 'L yMri.
diarrhea · .. of f1g11 In North f11tll11. I Jl~h~ rl~ki ~mup~ lwfocfo suf1jt<.fq
cow milk Onset of diarrhea af tar Introduction of with 'l'yJm I dl11huh1H n11tfllt11ti1 I >11V111 1;yn11tt1t1H! , ~ lttctlv~
protein allergy cow or buffalo mllk or formula 1¥,t\ d11 lr J1111ry 1 iwtol1n111111111 thymld tflc;Msl!, Turner
Rectal bleeding (due to colllliJ) HY nd ""' 11111Wll Il11m1:1tiy1HI,.,1n11r1'"'''1111111111t111 llvt<r d IM!;lc:e
Anemia; failure to thrive rtnd fl1'til,if1•w1•11nd11tlw#11( 1•1,llm: 11lt;.4!1tt;t• 1 1t1tfo11 f~, ·1tww
Family history of allergy or atopy Ht1l>J1 1r.IH 1"11''' f11 illl l111:mHH1·d rl11k 11{ cl1•vt•l11plt1r, udlac
Response to milk withdrawal dlM•1rn1111ml 1h11H 11h1111ld Im 1;cri•wwtL
Lymphangiectasia Nonplttlng pedal edema suggesting P1·1 fJ1•11f 111/11111 '1'111• d11hnlrnl pn1 ~:t•11l n tl1111 ic; v11tti Mntill
1
lymphedema
how11I dlr11'rlwa, wowth (11111,,'11 11wl 11111•111ln, ;, tf!rnJJ"'"'
Recurrent anasarca
llHH<>d11tlo11 o( dlarrlw11,wd l11fr1Jd1u tl111111f whi·al pmduct~
Hypoalbumlnemla and hypoprotelnemla al wwrnlnK may he pri:111•11 L <>111;1:t 1,f c.Jl11t1h1:i1 bd1m.!
Lymphopenla
Hypocalcemla
lntmd11r llon of wlw11t pr111l11<:ff) 111 dl1·t m:y11t1•-;;. ;1 diilf'Jl'Y,;19
of C!llllar. 1lltH•arH:. ll may nlrio pr••()elft wlU11rut dmmlc
cystic fibrosis History of meconlum lieus dlMrhi•11;m rd rndory lr1111 d1·(kl1·11Gy '" dl111rJrphlc ancrnla
Predominant or associated lower not r1•hpondlt1K 111urnI 1i llppl1:1111·11t ~, ::hurt f~lt>furn, delayed
respiratory tract Infections
p11lwrly1 rkkulH a11d 1111l!:f1Jll'tila. l ~/.il trdri<J tlcm rt-V!!a l~
Severe failure to thrive
Clubbing
fnll11re l.o lhrlV(!, loriN of 1>tiht1Jli111l'11ui. fat, clubbing,
tltrnml;i, rkkclH;rnd 1)1~111) uf 11tl11rr ·1lt11111ln <.fofi ch:ndes.
History of sibling deaths
High sweat chloride (>60 mEq/L) A hl~h lncl l:x of But>pklon for <A:llt:u; dlt,ct.J:;c IE> the key
to dh1gno1}ltt.
·1mmuno- Predominant fever
'deficiencies Recurrent Infections Involving other sites /Jla;.:11m1fn: The maln lnVC!)tlgaUonn rcquln:d for m;,ikir1g
! ,.
History of sibling deaths a dlagncmlHInclude:
Organomegaly I. fil'Yolo:-:y: lgA antib<Jdy t114aln11t tl~;u e tr'1mglutarnina.w
Opportunistic Infections on stool (l'fCJ ls; an 11.LISA b<rned h;t;t, n:cwnrnt.'f'lded fm initial
examination iefltlng of cellac dit~Ct.11>1~. It }w!> a hiy)i t-t-nsi tivity ('J2-
100%) and npeciflclly ('J1-l()(fi..) in both childn:n and
In young children, celiac disease is the most common a<lultr?. lgA nntiencJomyni'1 1 1mtlh(Jdy is ;sn equally
cause of chronic diarrhea in North India. Cow milk protein accurate k Hl (BcnHitl vil y fW,- l()()'ir1; npedfidty 91 - 1()(fir,)
allergy usually resolves by 3-5 years; hence, this diagnosis but iH mored ifflcult l11 p1:rform. ·nw diagn0<:i•; of celiac
should not be considered in children with onset of diarrhea dilwc:wc Ahould nol b1~ ba1~ec.1 only on celiac serology as
beyond 5 years. Toddler diarrhea is a diagnosis of exclusion Rcrology may be fol iw p<1•1itiv1!, folr~c n cg<l tivc and
after common causes have been ruled out. The onset of lnlcrlaboratory varialion!i an: al•.o pres1:nt.
diarrhea is between 6 months and 3 years of age. The child ii. Uppa Cl l!lld<JljCopy: It may be r1urrnal (Jr &how ab~ence
passes 3--6 loose stools, mostly during waking hour. of foldHor Bcalloped folcfo (Fig. 12.16a). Multiple (4-6
Diarrhea worsens with low residue, low fat or high in number) cnd o~copic blop9ic~1 from the bulb and
carbohydrate diet. The child is well thri~ing, there is no Hecond/lhird part of duodenum 1-J hould be t<lkcn in
anemia or vitamin deficiencies and the diarrhea resolves all cases.
spontaneously by about 4 years of age. Treatment is with iii. If itl /oloxy: The charactcrii;tic hi tologic<ll changt-s in
dietary modification; a high (>40%) fat, low c~r~ohydratc ccllac dl1:1casc arc in crca~d inlracpithelii11lyrnphocytes
~iet (especially with decreased intake of iu1ce~) and (>30/100 cnlcrocylc1:1), incn:aq:d crypt lcn ~th , partial
mcrease in dietary fiber is recommended. IBO is less to total villou1:1 atrophy, decrl!<l!'A!d vi llou!f to crypt ratio
common in this age group as compared to older children. and infiltration of pltu1mn cells an<l lymphocytes in
Giardiasis can be diagnosed, if multiple fresh stool.samples lamina propria (Pig. 12.16b).
(at least 3 in number) are tested for troph~zo1tes. The Ditt~no!;lis of ccliac dit;cMiC (bnscd on the modified
laboratory may be asked to use concentration met~odB . criteria of lhc European Society of Pediatric Gastro-
Presence of cysts of giardia in ~m~u~ocompetent patients cntcrology, llcpalology and Nutrition, ESPGHAN)
does not merit a therapy of giard1as1s. require the following:
Limited etiologies cause chronic .di~rrhca in older I. Cllnlcal fcalurC!:I compatible with diagnosis.
children (Table 12.16). A brief description of common ii. POf1itivc intc1:1 tim1l blopi;y il~ described above with or
caUses of chronic diarrhea is given below. without Bcrology.
iii. Unequivocal wspon c to gluten-free diet (GFD) within
Cenac Disease 12 wcckff of lnitl<1llon of Cl1D.
This IS. an enteropathy caused by permanent .sensitivity
h
A poi;ltlvc i;crology makctl the dic:ay,nosis more definite
to gluten in genetically susceptible subjects. It lB t c most capccittlly in developing countrlcu where other cauS<.>S of
20R I EssenUal Pediatrics
Fig. 12.16: Colloc dl~r,a:io: (a) IJpJ')€r gastrointestinal endor.>eopy showing scalloping of duodenal folds (arrow); and [b) Duodenal
hlGfology ohowlng to tal v111ou:i atrophy
vii Immillrophy nrc common due to intercurrent infections of milk intake and is characterized by vomiting, pallor,
or 1mdcrn11lrition. shock-like state, urticaria and swelling of lips. (ii) Delayed,
'flw rcccmt ESPC HAN guidelines s uggest that in Le. T cell mediated: It has an indolent course and presents
Hymptomalic paticnl!i with tTC >10ULN, the diagnosis of mainly with GI symptoms.
ccliac diRcaAc mny be made without a duodenal biopsy Symptoms: The most common presentation is with
provided that the nntiendomysinl antibody and HLA diarrhea with blood and mucus. Depending upon the site
DQ2/DQ8 nre po~itive and there is a definite response to and extent of involvement, the child may have small
gluten-free diet. However, in view of non-availability and bowel, large bowel or mixed type diarrhea. In an Indian
cost of nnlicndomysinl antibody and HLA testing and study, 40% children presented with bloody diarrhea, 33%
multiple labs reporting tTC as positive/negative only watery and 7% with a mixed ty pe of diarrhea.
without nctual titres this approach is not recommended Uncommonly reflux symptoms and hematemesis may be
In our country nt present. Thi s is especially important as present indicating upper GI involvement. Respiratory
it IR very difficult to confirm or refute the diagnosis of CD symptoms (allergic rhinitis and asthma) and atopic
nftcr initintion of GFD. Thus all efforts should be made to manifestations (eczema, angioedema) may be seen in
mnkc a correct diagnosis with full work-up at onset prior 20-30% and 50-60% cases, respectively. Iron deficiency
to initiation of GFD. anemia, hypoproteinemia and eosinophilia are conunonly
Trt!afmcnl': The treatment involves lifelong GFD and present.
correction of iron, folatc and other vitamin/mineral Diagnosis: In India, non-IgE-mediated C:MPA is more
deficiencies by supplementation. The patient should be common. Sigmoidoscopy (aphthous ulcers and nodular
Parental education regarding diet and calcium supplemen- mucosa. On UGI endoscopy after fat loading with 2 g/kg of
tation is essential. butter at bedtime, scattered white plaques or chyle-like
substance covering the mucosa may be seen (Fig. 12.18a).
Intestinal Lymphanglectasla Duodenal biopsy reveals dilated lacteals in villi and lamina
It is characterized by ectasia of the bowel lymphatic propria (Fig. 12.18b). The treatment consists of a low fat,
system, which on rupture causes leakage of lymph in the high protein diet with MCT oil, calcium and fat-soluble
bowel. The disease is often associated with abnormal vitamin supplementation. Intravenous albumin is
lymphatics in extremities. Signs and symptoms include required for symptomatic management and total
peripheral edema which could be bilateral and pitting due parenteral nutrition (TPN) is reserved for management
to hypoalbuminemia or asymmetrical and non-pitting due of chylous effusions. Resection may be considered, if the
to lymphedema tous limb. Diarrhea, abdominal distension lesion is localized to a small segment of intestine.
and abdominal pain are commonly present. Abdominal
Immunodeficiency
and/or thoracic chylous effusions may be associated.
Presence of hypoalbuminemia, low immunoglobulins, Both congenital and acquired immunodeficiency can cause
hypocalcemia and lymphopenia is characteristic of chronic diarrhea. It should be suspected, if there is history
lymphangiectasia. Barium meal follow-through shows of recurrent infections at multiple sites (chest/GI / skin)
thickening of jejuna! folds with nodular lucencies in and wasting. The common immunodeficiency conditions
~~~~mllldi~
~g, 12.18: Intestinal lymphanglectasla. (a) Upper gastrointestinal endoscopy showing white deposits: and (b) Duodenal histology
ows dilated lacteals
- aoo I Essential Pediatrics
presenting with diarrhea include IgA deficiency, severe · Protozoa. Microsporidium, Isospora belli,
lV. . . G . d. l bl .
Cryptosp~di
'lint
combined immunodeficiency (SCID), common variable Entamoeba hzstolytzca,
. .
zar za am za, Cyclospora,'
immunodeficiency (CVID) and chronic granulomatous Blastocystis hommzs
disease (CGD). There is increased risk of celiac disease Multiple stool examinati?ns are re~uired ~o identify the
(10-20-fold increase) and Crohn's disease in patients with causative etiology by u_sm~ spec1~l stams and PCR
lgA deficiency. Diarrhea is either due to enteric infections techniques. Colonic/ termmal ileum biopsy and duodenal
like giardia, cryptosporidium, CMV, etc. or due to bacterial fluid examination are the other ways of diagnosin
overgrowth. Diagnosis is made by measuring serum opportunistic infections. Treatment is with specifjg
immunoglobulins, T cell counts and functions, phagocytic antimicrobials (Table 12.17) along with HAART (hight;
function (nitroblue tetrazolium reduction test) depending active antiretroviral therapy).
upon the suspected etiology. Treatment involves
ndministration of antimicrobials for bacterial overgrowth Drug-Induced Diarrhea
and opportunistic infections and therapy for underlying Diarrhea can be a side effect of many pharmacologic
cause (IV immunoglobulins, y interferon or bone marrow agents. Altered GI motility, mucosa! injury and/ or change
transplantation). in intestinal rnicroflora are the main etiologic factors. Anti-
Acquired immunodeficiency syndrome (AIDS): Chronic biotics can cause loose watery stools by altered bacterial
diarrhea is a common feature in children with AIDS. The flora or bloody stools secondary to Clostridium difficile
impaired mucosa} immunity results in recurrent overgrowth and pseudomembranous colitis (PMC).
opportunistic infections and the altered maturation and Stopping the offending agent is often enough. If suspicion
function of enterocytes results in increased permeability of PMC is present then stool for toxin assay and sigmoido-
and decreased functional absorptive surface with or scopy is required for confirmation. Metronidazole or oral
without bacterial overgrowth. AIDS enteropathy is vancomycin is the drug of choice for PMC.
characterized by chronic diarrhea and marked weight loss
in absence of enteric pathogens. The children are often Inflammatory Bowel Disease (IBD)
sick with other clinical manifestations but sometimes IBD is a chronic inflammatory disease of the GI tract and
diarrhea may be the only symptom. Presence of oral is of two main types, Crohn's disease and ulcerative colitis.
thrush, lymphadenopathy, hepatosplenornegaly and In -10% cases, the findings are non-specific and subjects
parotiditis (10-20% cases) gives clue to the diagnosis. The cannot be classified into one of the above two groups.
common infections include: These cases are labelled as indeterminate colitis. Nearly
i. Vim!. Cytomegalovirus, herpes simplex, adenovirus, 25% of all IBD presents in the pediatric age group.
norovirus Worldwide the incidence of IBD is increasing in children
ii. Bacterial. Salmonella, Shigella, Mycobacterium avium with increase in recent reports of both ulcerative colitis
complex (MAC), Campylobacter jejuni, Clostridium diffidle and Crohn's disease from India. The average age of
iii. Fungi. Candidiasis, histoplasmosis, cryptococcosis presentation in children is -10-11 years. Genetics is a very
--·--·
•
. ·-- --··-~----
Table 12.17: Treatment recommendations for infectious d·iar-rhea-· -
iJllPortant risk factor for IBD and up to 30% patients may perianal and rectal examination for fistulae, tags and
1tave a family member with IBD. fissures is essential. Simple lab tests like hemogram, ESR,
cli11ical feahtres: Children with ulcerative colitis present C reacti,·e protein, total protein, semm albumin and stool
,dth diarrhea and rectal bleeding which raises alarm and for occult blood helps in screening for IBD and confirming
leads to early workup and diagnosis. In Crohn's disease, presence of bowel inflammation. Fecal caJprotectin is a
abdominal pain, diarrhea and growth failure are the reliable test for differentiating patients with functional
predo~ant ~omi:>laints. The classical triad of Crohn's abdominal pain from those with abdominal pain due to
disease, i.e. pain, diarrhea and weight loss is seen in only inflammatorv conditions like Crohn's. It is raised in IBD
J
25% cases. Fever, fatigue and anorexia are present in and normal in FAP.
25-50% cases. The absence of blood in stools and According to the recommendations of the IBD working
non-specific complaints are responsible for delay in group, upper GI endoscopy with biopsy, colonoscopy
diagnosis of Crohn's disease in children. with ileal intubation and biopsy is essential for all cases
Extraintestinal manifestations are seen in 25-30% (Fig. 12.19). Small bowel e' aluation with CT or MR
children with IBD. They can precede, follow or occur enterography should be done for correct classification into
concurrently with the intestinal disease and may be ulcerative colitis or Crohn's disease and to determine the
related/unrelated to activity of the intestinal disease. disease extent. Capsule endoscopy may also be used for
Arthralgia/ arthritis is the most common extraintestinal small bowel evaluation in patients who do not ha,·e any
manifestation seen in 15-17% cases. Uveitis, erythema suggestion of an obstructive (stricturing) lesion of small
nodosum and sclerosing cholangitis are the other extra- bowel.
intestinal manifestations.
Treatment: The goal of treatment is to control inflamma-
Disease distribution: Ulcerative colitis is classified as tion, improYe growth and ensure a good quality of life
distal colitis (proctitis/proctosigmoiditis), left side colitis with the least toxic therapeutic regimen . As IBD is a
(up to splenic flexure) and pancolitis with majority of chronic disease with remissions and exacerbations, proper
children having pancolitis. Majority of patients with counseling of both patient and family at diagnosis is
Crohn's disease (50-70%) have ileocolonic disease, with essential. The main drugs used for IBD are 5 amino-
isolated colonic involvement in 10-20% and isolated small salicylates (5-ASA), steroids and immunomodulators
bowel in 10-15% patients. Upper GI involvement is (6-mercaptopurine, azathioprine, methotrexate and
present in 30-40% cases and perianal disease in 20-25% monoclonal antibodies against tumor necrosis factor, i.e.
cases. Crohn's disease is also classified as predominantly infliximab). Ensuring proper nutrition with caloric
inflammatory, fistulizing or stricturing disease based on supplementation (-120% of RDA) is a necessity for
the clinical features. children with IBD. Calcium and vitamin D supplemen-
As the management and prognosis of Crohn's disease tation should be given as these children are at an increased
and ulcerative colitis is different, so a correct diagnosis is risk of osteoporosis.
essential. Table 12.18 lists the main differentiating features Surgery is indicated in ulcerative colitis patients \\ith
between ulcerative colitis and Crohn's disease. severe acute colitis refractory to medical diseas e.
Diagnosis: The initial evaluation of a child with suspected Uncontrolled hemorrhage, perforation, toxic megacolon,
IBD includes a detailed clinical, family and treatment abscesses and obstruction are the other indications for
history. A complete examination with growth charting, surgery in patients with IBO .
.
Table 12.18: Differentiation between Crohn's disease and. ulcerative colitis .
Crohn's disease Ulcerative colitis
Entire gastrointestinal tract Colon only
Discontinuous lesions Continuous involvement
BloOdy diarrhea Less common Common
·Abdominal pain Common Less common
. Growth failure Common Less common
· Perianal disease Abscess; fistulae Absent
Serology Anti-Sacchromyces cerevislae antibody Perinuclear anti-neutrophil cytoplasmic antibody
(ASCA) positive (p-ANCA) positive
Endoscopy Deep irregular serpigenous or aphthous Granularity, loss of vascular pattern, friability and
ulcers with normal intervening mucosa diffuse ulceration
(skip lesions)
' liistopathology Transmural inflammation with non- Mucosal disease with cryptitis, crypt distortion, crypt
caseating granuloma abscess and goblet cell depletion
.... - --
- 302 I
Fig. 12.19: Inflammatory bowel disease: (a) Deep, linear, serpigenous ulcers on colonoscopy In Crohn's disease; and (b) Confluerrt
superficial ulcerations with friability on colonoscopy in ulcerative colitis
Abdominal Tuberculosis
The gastrointestinal tract, peritoneum, lymph nodes and/
or solid viscera can be involved in abdominal tuberculosis.
The peritoneal involvement is of two types: Wet (or ascitic)
and dry (or plastic) type. On the other hand, the intestinal
involvement may be ulcerative, hypertrophic or ulcero-
hypertrophic type.
The clinical presentation is varied and depends upon
the site of disease and type of pathology. Clinical features
may include chronic diarrhea, features of subacute
intestinal obstruction (abdominal pain, distension, Fig. 12.20: CT scan showing multiple enlarged lymph r '.Jdes
vomiting, obstipation), ascites, lump in abdomen (ileocecal with central necrosis In para-aortic and mesenteric reg 1'.)r.s in
mass, loculated ascites, lymph nodes) and/or systemic abdominal tuberculosis
manifestations (fever, malaise, anorexia and weight loss).
A high index of suspicion followed by documenting
,,,,,,.,_-- ..~"": ·• -;
~ ~
..
..
_
Table 12.19: Common causes of up~er gastrolnt~stin~I bleeding
·Neonate or infant Children >2 years
Fig. 12.22: Upper gastrointestinal endoscopy showing (a) Esophageal varlces: and (b) Largo gastric varlcos
Administration of somatostatin or octreotide decreases parenchymn. The pnssngc is dilalc<l by a balloon and an
the splanchnic and azygous blood flow, thus reducing expansile mctnllk mesh prnRthesiR ls placed to maintain
portal pressures. Both agents are equally effective; limited the communication dlrcclly be tween the portal vein and
studies in children have shown control of bleeding in hepatic vein. This procedure rc::iults in bypassing li ver
64-71% children. Infusion should be given for at least resistance nnd consequently decreases the portnl pres urc.
24-48 hours after the bleeding has stopped to prevent Experience of l'his prncedurc in children is limited .
recurrence and should not be discontinued abruptly.
Endoscopic sclerotherapy (EST) or variceal ligation S11rgiC11/ ma1111g1•11u·11t is required when above measures
(EVL) are the two main methods used to manage have failed or when bleeding is from ectopic variccs that
esophageal varices. Using a fiberoptic endoscope, the cmmot be effectively contrnllcd by endoscopic procedures.
varices are inspected and their location, size and extent Surgery cnn be done either In the form of portocaval s~1u nt
are documented. In EST, 2-3 mL of sclerosant (1 % (selective or nonselective) or dcvascularization : ilh
ethoxysclerol) is injected into each variceal colunm. EVL esophageal staple trnnscction.
is done with a device called multiple band ligator. The
variceal column is sucked into a cylinder attached at the Lower Gastrointestinal Bleeding
tip of the endoscope and the band is deployed by pulling The cnuses of lower gastrointestinal bleeding in chilJren
the trip wire around the varix. Both EST and EVL have are shown in Tnble 12.20. History and physicnl ex<rnu11a·
90-100% efficacy in controlling acute bleeding. tion helps narrow down lhc differential din gn ·is.
()thers
Anal fissure Anal fissure
lntussusception Polyp or pofyposis syndrome
Duplication cyst Solitary rectal ulcer syndrome
Arteriovenous malformation Meckers diverticulum
Rectal prolapse NSAID-induced ulcer I
Meckel's diverticulum Hemorrhoids, rectal prolapse • t.
•
Hemorrhagic disease Henoch-Schonlein purpura ( .
of newborn Arteriovenous malformation
~\I ' ·
Coagulopathy Coagulopattiy
Fig. 12.23: Colonoscopy showing multiple sessile and
Tumors: Leiomyoma. lymphoma
pedunculated polyps in a child with polyposis coli
syndrome (SRUS). Intussusception is characterized by cutaneous lesions as seen in blue rubber bleb nevus
episodes of abdominal pain, vomiting and red currant- syndrome often suggests the diagnosis. Children with HIV
jelly stools, i.e. mixture of blood, mucoid exudates and infection or immunosuppression secondary to chemo-
stool. Painless bleeding is seen commonly in polyps therapy can develop CMV enterocolitis or polymicrobial
(Fig. 12.23), Meckel's diverticulum (Fig. 12.24), varices inflammation of cecwn (typhlitis), both of which can lead
(Fig. 12.25), ulcer or vascular anomaly. Presence of typical to significant rectal bleeding.
~· 12.24: Technetiu~~99m ~rtechnetate scan showing Fig. 12.25: Coionoscopy showing rectal varlx In a patient with
~s divertlculum EHPVO and lower GI bleeding
-3~ I t;1e1umtht1 P1dln1~,1~0-~1..=~==~===~~..,.____,----....
protlirombin time (P1J and international ncnmalfaed Table 1222: C:nrses oJ hepatomegaJy
ratio (INR): Deficiency of factors V and vitamin K
depefldent factors (II, Vll, IX and X) ocrnrs in liver disease. ~ Wer Q:ssase (cirrhosis or chronic hepatitis): Wilson
pr is a marker of synthetic function of Liver. ~""R is a as.ease. chroJlic he;:r..!ffis B and C, autoimmune fNer disease
B~ S)'TY'~-ne, cryptogenic '
standardized way of reporting the prothrombin time. It is
the ratio of a patient prothrombin time to a rumnaI sample, M=taro!ic or storag3 disorders. Glycogen storage disease,
raised to the power of the international sen...c;itiritv iruiex Gaut:her cflse::...se, Nierrenn-Pick disease, progressive familial
imrc:hepalic c:OOle:.-tas?s, nonalcoholic fatty liver disease
(JSI) value for the analytical system used. rs(ranves
between 1.0 and 2.0 and shows how a batch of tissue ractm lrrfedive; Viral hep::-Dtis, Uver abscess (pyogenic or amebic),
tuberculoSs. sa1-none!la, malaria, kala-azar, hydatid disease
compares to an internationally standardized sample.
Tumcrs: Lymphoma, ~eu'kemia, histiocytosis, neuroblastoma,
INR = (PT test/PI nonna1)151 benign hemans:oendcthel.ioma, mesenchymal hamartoma,
hepatoblastoma, hepatocellular carcinoma
The reference range for prothrombin time is usually
around 11-16 seconds; the normal range for the IN9R is BifJaJy. carou disease. choledochal cyst, congenital hepatic
fibrosis, cystic disease of liver, extra.hepatic biliary obstruction
0.8-1.2. A prolongation of PI by >3 seconds is abnormal
Miscellaneous: Congestive heart failure, constrictive peri-
Serum. p~oteins: The half-life of albumin is 20 days; carditis. ~
alburrun IS a marker of liver synthetic functions and is low
in chronic liver disease. Gamma globulins are increased
in autoimmune hepatitis; the ratio of albumin to globulin Table 12.23: Common causes of splenomegaly
is reversed in cirrhosis, particularly in autoimmune liver Portal hypertension: Cirrhosis, extrahepatic portal venous
disease. Low serum albumin and prolonged PT (un- obstruction; congenital hepatic fibrosis, noncirrhotic portal
fibrosis, Budd-Chiari syndrome
responsive to vitamin K) indicate poor synthetic liver
functions, raised ALT and AST indicate inflammation and Storage disorders: Niemann-Pick disease, Gaucher disease,
raised ALP and GGT suggest cholestasis. mucopolysaccharidosis
Hematological malignancies: Leukemia, lymphoma,
Serum ammonia levels: Levels are raised in hepatic histiocytosis
encephalopathy.
Increased splenic function: Collagen vascular disorders,
Cliolesterol: Levels are increased in cholestasis. autoimmune hemolytic anemia, inherited hemolytic anemias
Infections: Malaria, enteric fever, viral hepatitis, infectious
Liver Biopsy mononucleosis, kala-azar; congenital infections
Biopsy is a useful investigation for making a histologic Extramedu/fary hematopoiesis: Osteopetrosis
diagnosis especially in neonatal cholestasis, congenital
hepatic fibrosis, storage disorders like glycogen storage Liver Abscess
I
diseases and histiocytosis. It is useful for enzymatic Pyogenic liver abscess is more common than amebic liver
estimation in metabolic diseases and for copper in Wilson abscess in children. The infection reaches the liver by one
disease. It is helpful in diagnosis of infectious diseases by of the following routes: (i) portal vein, e.g. in intra·abdominal
immunohistochemistry and monitoring response to sepsis, umbilical vein infection; (ii) biliary tree obstruction
therapy. Liver biopsy also helps in understanding the and cholangitis, e.g. choledochal cyst; (iii) systemic sepsis,
stage of liver disease, e.g. chronic hepatitis or cirrhosis, e.g. endocarditis, osteomyelitis; and (iv) direct inoculation,
degree of fibrosis and inflammation (see Chapter 29). e.g. in trauma. In children on immunosuppressive
medications or with defects of neutrophil function (e.g.
Hepatomegaly chronic granulomatous disease), there is an increased risk
A palpable liver does not always indicate enlargement. It of developing abscesses, especially due to S. aureus. In
only reflects the relation of the liver to adjacent structures. children with liver abscess without cholangitis or
In normal children, the liver is palpable one cm and in pyelophlebitis, gram-positive infections are the commonest.
infants up to 2 cm below the costal margin. It is important Invasive intestinal amebiasis can lead to amebic liver
to measure the liver span to determine the presence of abscess although a history of amebic colitis in the preceding
hepatomegaly (Table 12.22). The liver span varies with age: period is not common. Amebic liver abscess is usually
Infants 5-6.5 cm; 1-5 years: 6-7 cm; 5-10 years: _7-9 cm; solitary and in the right lobe of liver whereas pyogenic
and 10-15 years: 8-10 cm. The liver is also examined for abscesses may be multiple (secondary to cholangitis) or
tenderness, consistency and character of the surface. single. Nearly three quarters of pyogenic liver abscesses
are in the right lobe of liver.
Sptenomegaly Clinical feah1res: The child presents with fever and right
Common causes of splenomegaly are listed in Table 12.23. upper quadrant abdominal pain. Jaundice is uncommon.
~Xrlh1h1<1tlon reveals tender hepatomegaly. Empyema, rupture (narrow rim <1 cm) .. Surger~ is req~ired for
pneumonia, subphrenic abscess and cholecystitis can have abscesses complicated by frank mtra~entoneal rupture or
a slmih1r clinical presentation and should be differentiated. multiseptate abscesses n~t _re~pondmg to percutaneous
Cumplications include spontaneous rupture into catheter drainage and antibiotics.
peritoneum, pericardium, pleura or bronchial tree and Prognosis: The abscess cavity. takes 3-6 months t~ resolve
metastatic spread to lungs or brain. completely. Cure rate following management with anti-
Dlng11osls: Leukocytosis and elevated ESR are usually biotics and percutaneous drainage is excellent.
present. Transaminases and alkaline phosphatase are
miJdly elevated. X-ray abdomen shows an elevated right Liver Tumors
dome of diaphragm with or without pleural effusion. Liver tumors account for -0.5-2% of all neoplasms in
Diagnosis is confirmed by imaging; ultrasound provides children. Hepatoblastoma, hernangioendothelioma and
good details about abscess size, number, rim and mesenchymal hamartoma are seen prirnarily in young
liquefaction. Contrast-enhanced CT scan may be required children whereas hepatocellular carcinoma, undifferen-
ln patients with complications (Fig. 12.27). Amebic tiated embryonal sarcoma and focal nodular hyperplasia
serology (indirect hemagglutination test) is positive in present in the older child. The most common tumors are
>95°!., children with amebic liver abscess and helps to hepatoblastorna, hepatocellular carcinoma and infantile
differentiate it from pyogenic abscess. However, in the hemangioendothelioma.
developing world, amebic serology may be positive due Infantile hepatic 1iemangioendot1relioma is a benign
to prior intestinal amebiasis and thus a negative amebic tumor and presents mostly in first 6 months of life with
serology helps exclude amebic liver abscess. an abdominal mass. Jaundice, skin hernangiomas and
Management: Patients with pyogenic liver abscesses are congestive heart failure may be associated. The lesion may
treated with broad-spectrum antibiotics (against gram- be single or multiple and is made of thin vascular channels.
positive-to cover for Staphylococcus aureus, gram-negative Observation is recommended for focal lesions. Treatment
aerobic and anaerobic bacteria) for 4-6 weeks . options for multifocal and diffuse lesions include
Metronidazole is used for 10-14 days in patients with corticosteroids, propranolol, hepatic artery ligation with
amebic liver abscess. Ultrasound-guided percutaneous or without corticosteroids, hepatic artery embolization,
needle aspiration and I or catheter drainage is required for surgical resection or liver transplantation.
abscesses that foil to improve after 3-4 days of antibiotic Hepatoblastoma is the most common malignant liver
therapy, large abscess in left lobe and those with impending tumor in children. It is of two types: Epithelial (fetal or
embryonal malignant cells) and mixed (epithelial and
mesenchymal elements) and presents with an abdominal
mass and anorexia. Weight loss and pain in abdomen
usually appear late; metastasis occurs to lungs and lymph
nodes and alpha-fetoprotein is raised in the majority of
cases. Ultrasound helps to differentiate between malignant
and vascular lesions. CT and MRI are used to define tumor
extent and resectability (Fig. 12.28). The survival of
patients with a hepatoblastoma has markedly improved
m recent years by combining surgery with pre- and
postoperative chemotherapeutic agents such as cisplatin
and doxorubicin. Liver transplantation is an option for
unresectable hepatoblastoma following chemotherapy in
absence of visible extrahepatic disease.
Hepatocellular carcinoma is usually multicentric. The risk
is increased in patients with chronic hepatitis B or C
infection, tyrosinemia, glycogen storage disease or prior
androgen therapy. The tumor presents as a liver mass with
abdominal distension, anorexia and weight loss. Liver
functions are usually normal and anemia may be present;
alpha-fetoprotein is raised. Imaging with CT /MRI helps
in defining tumor extent, resectability and metastasis. Bone
Fig. 12.27: Computed tomography scan shows a multl- scan and CT chest should be done to screen for distant
loculoted llver abscess In the right lobe (black arrow) with metastasis. Treatment options include surgical resection
elevofed right dome of diaphragm and ascites. Percutaneous along ·with chemotherapy; chemoembolization and liver
drainage cofhefer Is seen Jn situ (white arrow) transplantation.
Diseases of Gastrolntestlnal System and Liver I 309 I
I
Tabie.12.24: Causes of Jaundice in children
Uncon)ugated hyperblllrublnemla
Hemolysls: Blood group incompatibility (Rh, ABO), drugs,
infection related, glucose-6-phosphate dehydrogenase
deficiency, autoimmune hemolysls
Blllrubln overproduction: Ineffective erythropoiesis, large
he mato ma
Specific conditions In neonates: Physiologic jaundice, breast
milk jaundice
Enzyme defects: Gilbert syndrome, Crigler-Najjar syndrome
Miscellaneous: Hypothyroidism, fasting
Conjugated hyperblllrublnemla
Neonatal cholestasis
Infections: Sepsis, acute viral hepatitis, enteric fever, malaria,
leptospi rosis
Chronic liver disease
Fig. 12.28: CECT showing a large hepatoblastoma Liver tumor: Primary, secondaries
Infiltration: Histiocytosis, leukemia
Suggested Reading Enzyme defects: Dubin-Johnson syndrome, Rotor syndrome
• Srivastava A, Yachha SK, Arora V, Poddar U, Lal R, Baijal SS. Biliary: Choledochal cyst, choledocolithiasis, ascariasis,
Identification of high-risk group and therapeutic options in children sclerosing cholangitis
with liver abscess. Eur J Pediatr 2012; 171:33-41. Miscellaneous: Drug toxicity (hepatocellular, cholestatic), total
• Dezsofi A, Mc Lin V, Hadzic N. Hepatic meoplasms in children: a parenteral nutrition, veno-occlusive disease
focus on differential diagnosis. Clin Res Hepatol Gastroenterol
2014; 38:399-402.
• Kremer N, Walther AE, Tiao GM. Management ofHepatoblastoma: population. It results from a partial deficiency of the
an update. Curr Opin Pediatr 2014; 26:362-9. enzyme uridine diphosphate glucuronyl transferase
(UDP-GT) and thus, impaired conjugation. Most patients
Jaundice
are asymptomatic and exhibit chronic or recurrent
The term jaundice means a yellow discoloration of skin, jaundice (up to 6 mg/ dL) precipitated by intercurrent
sclera and mucous membrane due to increase in the serum illness, fasting or stress. Mild fatigue, nausea, anorexia or
bilirubin levels. Nearly 250-300 mg of bilirubin is abdominal pain may be present in some patients. Other
produced daily, approximately 70%_from breakd.o:wn ?f liver functions remain normal. No specific treatment is
old erythrocytes in reticuloendothehal system. B1hrubm necessary for this disorder.
is cleared by the liver in three steps. It is fi~s~ tran~ported
Crigler-Najjar syndrome (CN) type I is an autosomal
into hepatocytes by specific carriers. Then it is con1.ugated
to 1-2 molecules of glucoronide. Thereafter, the con1ug~te_d
bilirubin moves to the canalicular membrane where It 1s
recessive disorder characterized by absence of UDP-GT
activity. Patients develop severe unconjugated hyper-
bilirubinemia and die by 18-24 months of age, if untreated.
1
excreted into the bile canaliculi by other carrier proteins. Phototherapy, plasmapheresis and exchange transfusion
Most of the conjugated bilirubin is excreted ~ th~ stool are required for managing these cases in initial phases.
and small amount is reabsorbed after decon1ugation by Serum bilirubin levels should be kept below 20 mg/ dL
colonic bacteria. Colonic bacteria also reduce bilirubin to during first several months of life to prevent brain damage.
urobilinogen which is reabsorbed and excreted in urine. Definitive treatment is possible by liver transplantation,
Serum bilirubin should be >2.5-5 mg/ dL for jaundice preferably auxiliary, if available.
to be visible. Hyperbilirubinemia i.s classified as
Crigler-Najjar syndrome type II is also known as Aria
unconjugated (conjugated bilirubin fraction <15°/~ of total
syndrome. There is marked reduction of UDP-GT. In
bilirubin and normal colored urine) and con1ugated
comparison to type I, jaundice is less severe and does r:iot
hYPerbilirubinemia (conjugated biliru~~ fr~ct~on >20%
result in kernicterus. The condition responds to drugs like
With high colored urine). Conjugated ?~liru~m IS cleared
by kidneys; thus in renal failure, b1ltrubm levels are phenobarbitone that stimu~~te ~yperpl~sia. ~f the
endoplasmic reticulum. The b1hn:bm leve~ ~1grufi_cantly
~creased. Any abnormality of the above steps can cause
decreases in type II CN following adm1mstratI~n of
Jaundice (Table 12.24). phenobarbitone, while no change is seen in type I patients.
Congenital Enzyme Deficiencies Dubiu-/olmson syndrome is an autosomal .rec~ssive
Gilbert syndrome is the most common c:use of disorder resulting from impaired hepatic. ~xcre.tion ?f
Unconjugated hyperbilirubinemia and affects 3-8 Yo of the bilirubin and causes conjugated hyperbihrubmem1a
II S10 I E1aont1a1 Pediatrics
(2-6 mg/dL). Tho trnmrnmlmHws nnd synthetic liver lcptospirosis and vira l hemo rrhagic fever. Other
functions nre normnl. Most pntlcnts nrc asymptomntlc conditions that need to be diffe~entiated ~elude drug.
oport from jnundkc. Prcgnnncy ond oral contrnccpllvcs Induced hepatitis, acute presentation of autounmune liver
mny worsen j1nmdkc. Liver blopRy Is often dono for disease or Wilson d isease.
exclusion of othor cnugcs nnd showM brown-black
pigmcntlltion. lnvostlgatlons
RCJtCJr ~yu1lrcu111• Is n rnrc, outosomnl recessive disorder Direct hyperbllirubinemia with markedly elevated ALT/
mnnlfosting m; mild conjugntcd hypcrbillrublncmln. The AST and normal albumin and p rothrombin time are usual.
primnry defect nppcors to be n deficiency In the Mild Jcukopcnia with relative lymphocytosis is seen.
intmcell\llnr storngo cnpnclty of the liver for binding Ultrasound is not routinely required, but shows mildly
onions. The liver histology Is normol. enlarged liver with increased echogenkity and edema of
gallbladder wall. Viral serologies help determine the
ACUTE VIRAL HEPATITIS etiology of acute viral hepatitis, as shown in Table 12.25.
Viruses can affect tho liver, either primarily, e.g. hepatitis Complications
A, B, C, E or ns pnrl of n systemic involvement, e.g.
cytomegnlovirus (CMY), Epstcin-13arr virus (EBY), herpes These include:
simplex virus (HSV). In lndion children, hepatitis A is the i. Acute liver failure. The appearance of irritability, altered
commonest cnusc (40- 60 1Xi) of acute viral hepatitis, sleep pattern, persistent anorexia and uncorrectable
followed by hepatitis E ( l0-20'X,) and hepatitis B (7-17%). coagulopathy (despite administration of vitamin K)
Nearly 8-20% patients have coinfectlon with more than suggests the development of acute liver fail ure.
one virus, HAY and HEY being the commonest. Hepatitis ii. Aplastic anemia
A nnd E are transmitted by feco-oral route whereas HBY iii. Pancreatitis
and HCV are transmitted by parenteral or vertical (mother iv. Serum sickness, vasculitis-like reaction mav be seen
~
to baby) route (Table 12.25) (see also Chapter 11). in hepatitis B infection
v. Hemolysis (cola-colored urine) with rena l failure in
Cllnlcal Features subjects with glucose-6-phosphate deh ydroge!lase
Following exposure, patients show a prodrome charac- deficiency
terized by low grnde fever, malaise, anorexia and vi. Chronic liver disease: In patients with a cute ·.-iral
vomiting, followed by appearance of jaundice. Examina- hepatitis due to HBY, repeat testing for hepJ.ticis B
tion shows icterus, hepatomegaly and splenomegaly surface antigen should be done after 6 mon L~ to
(small, soft in 15-20%). Mild ascites may be present in 10- document clearance or persistence o f infectio;i. A
15% cases, which resolves completely on follow-up . Over majority (95%) clear hepatitis B infection afte: i cute
the next few weeks, the appetite improves, jaundice icteric infection.
resolves and the child gets better. In young children,
asymptomatic and anicteric presentation of hepatitis A Management
infection can occur. Maintaining adequate oral intake is ess entiul ,rnd
I Differential Diagnosis
The conditions, which mimic the clinical features of viral
hepatitis include enteric fever, falciparum malaria,
intravenous fluids are given, if persistent vomiting :md
dehydration are present. There is no advantage of enf reed
bed rest, but vigorous activity should be a\·oided . No
specific dietary modification is recommended. The child
Table 12.26:
pathy is classified into four stages (Table 12.27).
Identification of hepatic encephalopathy in children can
I
antibody hypotension, renal failure or presence of systemic
Cytomegalovirus PCR inflammatory response syndrome (temperature >38°C or
lgM varicella zoster virus, EBV viral <36°C, leukocyte count >12,000 or <4,000/ mm 3,
capsid antigen tachycardia). Antibiotic therapy is recommended for
Metabolic
Wilson disease Ceruloplasmin, Kayser-Fleischer
ring, 24 hour urinary copper Table 12.29;- Monitoring of children with -;cute liver failure
Tyrosinemia Urinary succinylacetone level . Pulse rate, respiratory ~~te, b~od pressure, temperature (q 4 hr)
Galactosemia Urine nonglucose reducing Intake-output charting (q 6 hr)
substances, galactose-1-phosphate Liver span, neurological monitoring, grading of coma (q 12 hr)
uridyltransferase level
Blood sugar, electrolytes, pH, bicarbonate, lactate (q 6-12 hr)
Autoimmune Anti-liver kidney microsomal
hepatitis Prothrombin time (INR) (daily)
antibody; antinuclear antibody; anti-
smooth muscle antibody; Complete blood counts, CAP (twice a week)
immunoglobulin levels Transaminases, GGTP, alkaline phosphatase, lactate dehydro·
Miscellaneous genase, total and conjugated bilirubin (twice a week)
Hemophagocytosis Triglyceride, ferritin, fibrinogen and Creatinine, calcium, phosphate (twice a week)
bone marrow biopsy Monitor as needed: Evidence of Infection on chest X-ray, blood
Paracetamol poisoning Plasma levels of paracetamol and urine cultures; blood ammonia
.
~ .-
Tabte 12.30: Specific treatment of conditions causing pediatric CHRONIC LIVER DISEASE
acute liver failure Chronic liver disease (CLO) refers to a spectrum of
N;; atal - Antioxidants: chelation; prena"tal intra- disorders characterized by ongoing chronic liver damage
hemochromatosis venous lmmunoglobulin in combination and a potential to progress to cirrhosis or end stage liver
with postnatal exchange transfusion disease. Although a 6-month duration rut off is used for
Tyrosinemia Nitisinone (NTBC); restriction of phenyl- defining chronicity related to hepatitis Band C, it does
alanine and tyrosine in diet not apply to the other causes as irreversible liver damage
Galactosemia Galactose and lactose free diet may have already taken place before symptoms of liver
Hereditary fructose Fructose free diet
disease are recognized.
intolerance Cirrhosis is a diffuse liver process characterized by cell
injury (necrosis) in response to inflamma~on/injury and
Mitochondrial Coenzyme 01 o, vitamin E, carnitine
cytopathies
fibrosis and regeneration (nodule formation). When the
disease is silent, the patient may have hepatosplenomegaly
· Amanita poisoning Penicillin G, silibinin and N-acetyl- and abnormal liver function tests and it is termed as
cysteine
compensated cirrhosis. When the patient dev elops
Herpes simplex High dose acyclovir (60 mg/kg/day) jaundice, gastrointestinal bleed, ascites and/ or.hepa~c
for 21 days encephalopathy, it is known as decompensated arrhOSIS.
Acetaminophen N-acetyl-cysteine (see Chapter 27)
poisoning Etiology
The main causes of CLO in children are listed in
Table 12.31. In India, -25% of CLD is due to metabolic
patients listed for transplantation. Antimicrobials with causes (Wilson disease being the commonest), 8-15% are
coverage against gram-positive and gram-negative due to hepatitis B and 2-4% due to autoimmune causes.
organisms (cefotaxime with cloxacillin) along with Nearly 40% patients do not have a known etiology, and
antifungals are used. Aminoglycosides are avoided to are labeled cryptogenic.
prevent renal dysfunction. Close monitoring and early
detection of infection is essential. Coagulopathy does not Clinical Features
necessarily warrant transfusion of fresh frozen plasma The presentation depends on the etiology and pace of
unless bleeding manifestations are clinically evident or disease progression. Patients may present with insidious
an invasive intervention is planned or INR is >7. Proton onset disease with failure to thrive, anorexia, muscle
pump inhibitions are used for stress ulcer prophylaxis. weakness and/or jaundice or abruptly with massive
In spite of adequate supportive care, the mortality in gastrointestinal bleed, acute onset jaundice, along with
ALF is as high as 60-70%. Early identification of children
who would benefit only from liver transplantation is fa-bie 12.31: Causes of chronic liver disease
essential. The King's College criteria are one of the
.Viral hepatitis Hepatitis B (common), hepatitis C
commonly used criteria to identify adult patients
(uncommon)
requiring liver transplantation. Application of these
Autoimmune liver Autoimmune hepatitis (common),
criteria in developing countries seems to be limited due disease autoimmune sclerosing cholangitis
to variation in etiology other than paracetamol induced
Metabolic Wilson disease, glycogen storage
liver failure. Young age (~3.5 years), bilirubin ~16.7 mg/ dL,
disease (IV)*, progressive familial
prolonged prothrombin time (>40 seconds) and signs of
intrahepatic cholestasis*, galactosemia*,
cerebral edema predicted mortality in an Indian study. NASH related, tyrosinemia*, Indian
Table 12.30 lists the specific therapy for common childhood cirrhosis* (rare), cystic
etiologies of ALF. fibrosis, hereditary fructose
intolerance*, alpha-1-antitrypsin
Suggested Reading deficiency, bile acid synthetic defects
• Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Venous obstruction Budd-Chiari syndrome, veno-occlusive
lancet 2010; 376:190-201. disease, constrictive pericarditis,
• Bhatia V, Bavdekar A, Yachha SK et al. Management of acute liver congestive heart failure
failure in infants and children: consensus statement of the pediatric Biliary Biliary atresia *, choledochal cyst*,
gastroenterology chapter, Indian Academy of Pediatrics. Ind Ped primary sclerosing cholangitis, Caroli
2013; 50:477-82. disease, Alagille syndrome
• Shanrnugam NP, Bansal S, Greenough A, et al. Neonatal liver
Rare causes Niemann-Pick disease, Gaucher disease;
failure: etiologies and management. Eur J Pediatr 2011; 170:573-81.
drug induced (valproate, carbamazepine)
• Srivastava A, Yachha SK, Poddar U. Predictors of outcome in
children with acute viral hepatitis and coagulopathy. JViral Hepat NASH: Nonalcoholic steatohepatitis
2012; 19:el94-201. *Causes in infants and young children <5 yr of age
• 314 I Essential Pediatrics
11! terod sensorium and ascites. Sometimes the patient may Table i 2.32i Investigations for chronic river diSe~
be asymptomntic and child is noticed to have hepato- Common Investigations
splcnomcgnly or elevated transaminases on investigations Liver function tests Low albumin, reversal of albumin-
for some unrelated illness. Clinical features on globulin ratio and prolonged
cxan1inntion thnt suggest presence of CLD are: prothrombin time
Clrnrnctcristlcs of liver. The liver may be firm to hard, High conjugated bilirubin suggests
nodular or have irregular margins in cirrhosis. Differential liver dysfunction or obstruction
left lobe enlargement is a feature of CLO. A small, non- Raised transaminases suggest
palpable shrunken liver is a feature of post-necrotic hepatocellular injury; raised alkaline
cirrhosis. phosphatase and gamma glutamyl
transpeptidase suggest biliary disease
Stigma ta of CLD: These include spider angiomata, palmar
erylhcma, clubbing, leukonychia, muscle wasting, delayed Ultrasonography Nodular liver, mass lesion, dilated
puberty nnd gynecomastia. Testicular atrophy and parotid portal vein and collaterals, ascites
splenomegaly '
enlargement are present in adults with alcoholic liver
disease, but not in children. Upper GI endoscopy Portal hypertension: Esophageal or
gastric varices
J>ortal liypertension: Splenornegaly, ascites, tortuous veins
over abdominal wall with flow away from umbilicus, i.e. Liver biopsy Breaking of lamina limitans and
caput medusae; esophageal varices with/without gastric lobular inflammation; nodule
varices on endoscopy. formation and loss of architecture in
cirrhosis; may also aid in diagnosis of
Fen hires ofliepa tic euceplralopathy: Asterixis, constructional specific diseases
apraxia or altered sensoritun (Table 12.27) may be seen.
Specific to etiology
Evaluation Viral markers HBsAg, HBeAg, anti-HBe, anti-HCV,
Evaluation of patients with suspected CLO is two- HBV DNA, HCV RNA
pronged: (i) determine etiology of CLD and (ii) assess Autoimmune Anti-smooth muscle, anti-liver kidney
degree of liver dysfunction and presence of complications hepatitis microsomal, antinuclear antibodies
(Table 12.32). Based on clinical and laboratory features, Wilson disease Ceruloplasmin, Kayser-Fleischer ring;
liver damage is graded using scores like the CHILD score 24 hours urine copper; liver copper
and pediatric end stage liver disease (PELO) score. Alpha-1-antitrypsin Serum alpha-1-antitrypsin levels; Pl
Complications of CLD are: (i) hepatic encephalopathy; deficiency type
(ii) portal hypertension with variceal bleeding, Ga!actosemia Positive nonglucose reducing
portopulmonary hypertension and hepatopulrnonary substances in urine; galactose-1 -
syndrome; (iii) ascites and spontaneous bacterial phosphate uridyltransferase .:issay
peritonitis; (iv) hepatorenal syndrome; (v) coagulopathy; Cystic fibrosis Sweat chloride test; genetic analysis
le Hepatic Encephalopathy
syndrome
Sclerosing
vein, inferior vena cava
Magnetic resonance cholangicpancreato-
Hepatic encephalopathy refers to neuropsychiatric cholangitis graphy; liver biopsy
abnormalities that result from liver dysfunction. It is a Storage disorders Bone marrow, fundus examination;
principal manifestations of CLO and can be graded liver biopsy
(Table 12.27). Various factors like gastrointestinal bleed,
infection, use of sedatives, dehydration due to aggressive disaccharides like lactulose and lactitol reach the colon
diuresis, constipation and electrolyte imbalance can intact and then are metabolized by bacteria into variety
precipitate encephalopathy. Identification and reversal of of small molecular weight organic acids. It. acts.:iY
the precipitating event is of importance. As ammonia is acidifying fecal contents and trapping the d1ffus 1 . ;
1
an important putative metabolite, efforts are targeted ammonia as ammonium ion in the fecal stream along '°". g
towards reducing its production and absorption and alteration in colonic flora (loss of ammonia produc~d
facilitating its excretion. Oral antibiotics and synthetic bacteria). In infants and children, protein intake .sho or
disaccharides have been shown to be effective in not be restricted to the point of causing growth failure ge
minimizing ammonia production in these patients. compromising overall nutritional status and a target rai;,Je
Neomycin was used in the past but it has serious side of 1-2 g/kg/ day is often recommended. V~geta ·ds
effects of deafness and renal toxicity. Rifaximin is a new proteins, which are rich in branched chain amin° aCl
drug with a better safety profile. Nonabsorbable are preferred over animal proteins.
Diseases of Gastrolntestlnal System and Liver I a1s 11
Nutrition Failure ASCITES
Children with end-stage liver disease are at risk for Ascites is the pathologic accumulation of fluid within the
developing nutritional compromise, which increases the peritoneal cavity and it can occur at any age and also in
disease related morbidity. The etiology of failure to gain utero. The main causes of ascites are given in Table 12.33.
weight in children with end-stage liver disease is Sometimes a large intra-abdominal cyst, i.e. cystic
multifactorial, due to a combination of decreased caloric lymphangioma, omental or ovarian cyst can masquerade
intake, increased energy expenditure, malabsorption of as ascites; this is known as pseudoascites.
macro- and micronutrients and altered physiologic
Evaluation: History and examination, imaging studies
anabolic signals. Children with CLD also have reduced
and paracentesis are required for ascertaining the etiology.
levels of liver-derived insulin-like growth factor 1, which
mediates the anabolic action of growth hormone and thus Patients present with increased abdominal girth ~nd
weight gain. Physical examination reveals ab~omm~l
a growth hormone-resistant state that negatively impacts
growth. distension, bulging flanks, shifting dullness, flmd thnll
and puddle sign. The liver and sp.leen ~ay be difficu~t to
Clinical recognition of malnutrition in infants and palpate in patients with tense asc1tes. Dilated abdominal
children with end-stage liver disease relies on careful collaterals and caput medusae may be seen in ascites due
monitoring for clinical features like growth failure, loss to liver disease, while collaterals in flanks and on the back
of muscle mass, delayed motor development or signs of suggest inferior vena cava block. Ele~ated jugular v~n~us
fat-soluble vitamin or essential fatty acid deficiencies pressure suggests a cardiac origm, e.g. constnchve
(skin rash, peripheral neuropathy, rickets/fractures or pericardi tis.
bruising). The presence of ascites, edema and organo- Ultrasound is a sensitive imaging technique for the
megaly makes weight an unreliable indicator of nutrition detection of ascites. Free fluid layers in the dependent
in a child with CLD. So height monitoring, along with regions, i.e. the hepatorenal recess (Morrison pouch) and
assessment of other anthropometric markers of body fat the pelvic cul-de-sac which is detected on ultras~u~d.
and muscle mass like triceps skin fold and mid-arm Abdominal paracentesis is a simple test for determlillilg
circumference should be used. the etiology. Diagnostic paracentesis should be done when
All patients need increased caloric intake -120-150% ascites is first detected, at the time of hospitalization, or
of their estimated daily requirements. Formulas when there is clinical deterioration with unexplained
containing medium-chain triglycerides are used ~o fever, abdominal pain or diarrhea. Ultrasound-guided tap
maximize fat absorption in the setting of severe cholestasis. is warranted in children with loculated ascites.
Daily supplements of vitamins and other nutrients like
Investigations: Ascitic fluid should be evaluated for total
calcium and iron need to be given. For patients who cannot and differential cell count, albumin level and culture.
meet the needs by oral feeding, nasogastric tube feedings Serum albumin is done to calculate the serum ascites
should be started. albumin gradient (SAAG), i.e. the concentration of
Patients with CLD are especially vulnerable to viral and albumin in serum minus its concentration in ascitic fluid .
bacterial infections. Careful attention must be given to - . .
ensure that all infants and children with CLD receive all Table 12.33: Causes of ascites
'
recommended routine childhood vaccinations.
Hepatorenal Syndrome
Hepatorenal syndrome is a functional renal ~pai~ent
I•common
Cirrhosis and portal hypertension
Budd-Chlari syndrome
Nephrotic syndrome
I
as changes are reversible after liver tr~plant. It is defined Protein losing enteropathy
as progressive renal insufficiency m absence of other Tubercular ascites
known causes (prerenal, nep~roto~ic drugs) of renal Constrictive pericarditis
failure in patients with severe liver disease. Cardiac failure
Chy/ous. Lymphatic obstruction, thoracic duct injury, intestinal
Suggested Reading
Dur d p New management options for end-
..Uncommon
: lymphangiectasia
I
treatment. Long-term administration of oral norrloxacin
m .renal sodium and water retention. (ii) Overfill theory: 5-7.5 mg/kg once a day in patients with cirrhosis and
Primary abnormality is inappropriate renal retention of ~sci tic protein content of <1 g/ dL or prior episode of SBP
sod~um an? water in the absence of volume depletion. is rec~mmended. Despite advances in supporti\·e care,
Basis of this theory is that patients with cirrhosis have bacterial peritonitis is an indicator of poor prognosis.
~~rava~cular hyp.ervolemia rather than hypovolemia.
(m) Peripheral arterial vasodilation: The chief cause of ascites PORTAL HYPERTENSION
is splanchnic vasodilation, which leads to decrease in
eff~ctive arte~ial blood volume. Progressive deterioration The portal vein is formed by the splenic and the superior
of live~ fun~tions, portal hypertension, splanchnic arterial mesenteric veins. Normal portal pressure is betwe~n
vasodilatation and reduced plasma oncotic pressure due 5 and 10 mm Hg and portal hypertension is an increase lll
to low serum albumin contribute to development of ascites. portal pressure of >12 mm Hg. It is a common clinical
situation in children and occurs due to increased portal
~anagement: For patients with ascites related to liver resistance and/ or increased portal blood flow. The
d1sea~e, mobilization of ascitic fluid is accomplished by pre~e~ce of esophageal varices on endoscopy is the mos~
c~ea~g a negative sodium balance until ascites has defllUte evidence of portal hypertension. The causes 0
dui:im~hed or resolved; then the sodium balance is portal hypertension may be either intrahepatic or
~amtamed so that ascites does not recur. Oral diuretic extrahepatic (prehepatic and posthepatic) (Table 12.34)·
(O ~PY consists of single morning dose of spironolactone
The spectrum of portal hypertension in children frof[l
· 3 mg/kg) along with furosernide (0.5-2 mg/kg), that
developed vs. developing world is different. In the former,
Dlaeaaea of Gaatrolnteatlnal Syetem and Liver 1317 -
Table 12.34: Causes of p ortal hypertension lnvasf/gattons
prehepatic Portal venous thrombosis, extrehepatlo The diagnosis of portal hype-rtens ion is made by the
portal venous obstruction (cavernous following investigations:
transformation of portal vein), Isolated
I. Ultrasound and Doppler study, The vascular anatomy
splenic vein thrombosis
ls defined and any block in portal, splenic or hepatic
lntrahepatic Liver cirrhosis (common), congenital hepatic · veins can be detected, Increased size of portal vein is
fibrosis, veno-occluslve disease, nonclrrhotlc
sugges tive of intrahcpatic p o rtal hypertension.
portal fibrosis, schistosomlasls, nodular 1
regenerative hyperplasia Presence of collaterals, asd t.£.-s, splc.'llomegal y and liver
abnormalities (altered echotexture, size and space
Posthepatic Budd-Chiarl syndrome (hepatic vein or
occupying lesions) are also seen.
Inferior vena cave obstruction), constrictive
pericarditis ii. Endoscopy can reveal varicc-s in esophagus, stomach
and congestive gastropathy.
intrahepatic causes of portal hypertension are most iii. Colonoscopy is useful in children with low er GI
common whereas in India, extrahepatic portal venous bleeding as it can show presence of rectal varices or
obstruction (EHPVO) is the commonest cause (50-75%) colopathy.
followed by cirrhosis (25-35%); uncommon causes are iv. Selective CT and MR portovenography are useful for
congenital hepatic fibrosis, non-cirrhotic portal fibrosis delineation of vascular anatomy.
and Budd-Chiari syndrome. Portal hypertension results v. Liver function tests are deranged in subjects w ith
in development of portosystemic venous channels at cirrhosis. Hemogram may show anemia, leukopenia
different sites giving rise to esophageal, gastric or colonic and thrombocytopenia that suggests hypersplenism..
varices. The main pointers which help in differentiating
Compllcatlons
portal hypertension due to cirrhosis from that due to non-
cirrhotic causes are shown in Table 12.35. The most common complication is GI bleeding secondary
to esophageal varices. Hypersplenism usually is not
Clinical Features symptomatic. The enlarged spleen is prone to splenic
The age of presentation ranges from infants to adults. A infarcts and accidental rupture with trauma. Other
majority of patients with EHPVO present with upper complications like ascites and hepatic encephalopathy
gastrointestinal bleeding and splenomegaly. Hematemesis occur frequently in children with cirrhosis.
and melena occur due to esophageal or gastric variceal Hepatopulmonary syndrome: The triad of chronic liver
bleeding. The bleed may be recurrent and is well tolerated disease or portal hypertension, alteration of arterial
without development of post-bleed hepatic encephalo- oxygenation (defined as widened age corrected alveolar
pathy. Splenomegaly alone is the presentation in 10-20% arterial oxygen gradient with or without arterial
cases. hypoxemia) and evidence of intrapulmonary vascular
Patients with portal hypertension due to cirrhosis have dilatations defines hepatopulmonary syndrome. Patients
jaundice, ascites, hepatosplenomegaly and less often, with hepatopulmonary syndrome present with dyspnea,
upper gastrointestinal bleeding. In Budd-Chiari syn- platypnea (dyspnea induced in upright position and
drome, patients present with ascites and hepatomegaly. reliev~d by recumbency) and orthodeoxia (arterial deoxy-
Tortuous prominent back veins are seen in Budd-Chiari genation accentuated in upright position and relieved bv
syndrome with inferior vena cava block. recumbency). Examination shows clubbing and cyano~.
Cllnlcal Presentation
Most children with chronic hepatitis C virus infection ~r~
asymptomatic or have mild nonspecific symptoms, wit
iii. One should screen all family members of HBsAg persistent or intermittently elevated or even normal seJ1Jl!l
positive patient for HBsAg. Vaccination of negative transaminases. Hepatomegaly may be present. Sever~
members against HBV and evaluating other HBsAg liver disease may develop 10-20 years. after o~set ~e
positive members for liver disease is required. infection, with a less than 2% overall nsk dunng 1
pediatric age group. .
Prevention of Chronic HBV Infection 15 1
The natural course of HCV infection in children n~c
Prevention is the most effective method of successfully clearly tmderstood, but overall advanced liver d'15~ase,..,
.
001
controlling HBV infection and its complications. The rare during childhood. In cases with vertical transrrus5~ to
hepatitis B vaccine is highly immunogenic with sero-
conversion rates of >90% after three doses. Antibody titers
spontaneous clearance of infection may be _seen d
7 years of age. Children with transfusion-acqwred e~an
tiOil
(anti-HBs) of >10 mIU/mL signify a response and are may have higher rates of spontaneous HCV clearance
protective. The dose in children and adolescents (aged less those with vertically acquired HCV infection.
Diseases of Gastrolntestlnal System and Liver I a21 -
m
IB
may present as clumsiness, speech difficulties, ~cholastic
deterioration, behavioral problems, convulsions and
choreoathetoid/dystonic movements.
both medications are given at a dose of 20 mg/kg1 daym
two divided doses.
Zi11c: Zinc has been used as acetate, sulfate or gluconate
salts. Zinc acts by inducing intestinal cell metallothionein,
Investigations
which binds copper to form mercaptides. The meta~lC:
Serum cemloplasmin is decreased (<20 mg/dL) in most thionine with copper is held in the intestinal cells until it
patients. In symptomatic patients, the 24 hours urinary is sloughed out. However, zinc is a slow-acting drug that
copper excretion is more than 100 pg/da~. Kayser- takes longer time to achieve a negative copper balance
Fleischer (KF) ring indicates long-standing disease and and is, therefore, effectively used as maintenance thera~Y·
severe copper overload. KF rings are more common in Liver transplantation is indicated in children with
children with neurological (96%) than hepatic (60%) and Wilson disease who present as acute liver. fa1·1 ure or have
asymptomatic (10-20%) Wilson disease. Hepatic copper decompensated cirrhosis unresponsive to medical therapY·
is the single best predictive marker and is considered to
be the gold standard, with values ~50 µg/ g dry weight of
Glycogen Storage Disorders .
liver. Liver biopsy is required for hepatic copper . . t '\etabohC
estimation. Mutational diagnosis is difficult because of the Glycogen storage disorders are importan . n r ical
occurrence of more than 200 mutations, each of which is disorders manifesting in childhoo.d with vaned le ftyp_e
rare. Mutational diagnosis is helpful in screening fami~y picture ranging from asymptomatic hepatomega Yd end·
members of an index patient homozygous for this VI) to hypoglycemia (type I, III) and decompensate
mutation. stage liver disease (type IV) (see Chapter 24).
Diseases of Gastrointestinal System and Liver
Type I glyco8CU storage disease (von Gierke disease): in transaminases. While hypoglycemia and hepatospleno-
I 323.
Inability to c~n~ert .g~ucose-6-phosphate to glucose in the megaly improve, 80-85% develop a myopathy in type ma
uver results 1~ 1~ab1hty to mobilize glycogen. Depending disease while the other 15% (type m b) have only liver
011 whether this is due to glucosc-6-phosphatase deficiency involvement. These cases are managed with diet similar
or translocase deficiency, it is classified as type lA or lB. to that in type I GSD, except that a high protein diet is
Hcp~tom~galy, doll-like fades (Fig. 12.30), hypo- preferred and there is no need to restrict galactose and
glycem1~, se1zu~cs, g~owth retardation, hyperuricemia, fructose.
hypertrig~yccridem1a and lactic acidosis are main
manifestations. Hypoglycemia is more marked after first
Type IV glycogen storage disorder: In type IV GSD there
is a deficiency of branching enzyme resulting in deposition
few months of life as the frequency of feeding decreases.
of an amylopectin like structure in the liver. The presen-
Liver adenoma might develop with risk of bleeding and
malignant transformation. tation is with chronic liver disease, portal hypertension
and hepatic decompensation. Most children are
Hepatomegaly and nephromegaly is appreciated on symptomatic by 3 years of age. Treatment is largely
imaging. Platelet dysfunction may be present. Neutropenia supportive and liver transplantation is required for
is specific to type 1 B. There is mild transaminase elevation. patients with advanced disease.
Liver biopsy shows hcpatocytes with vacuolated cytoplasm
and glycogen accumulation (PAS stain positive, diastase Suggested Reading
sensitive) along with microvesicular steatosis; fibrosis is • Clayton P. lnbom errors presenting "';th liver dysfunction. Semin
absent. Definite diagnosis depends on measuring enzyme Neonatol 2002; 7:4~3.
activity in the liver or mutational analysis. • Mayatepek E, Hoffmann B, Meissner T. Inborn errors of
Management hinges on providing a constant source of carbohydrate metabolism. Best Pract Res Clin Gastroenterol 2010;
24:607-18.
glucose in the form of slowly digested complex carbo- • Mazariegos G, Shneider B, Burton B, et al. Liver transplantation
hydrates. This is achieved by frequent daytime feeding, for pediatric metabolic disease. Mol Genet Metab 2014;111:418-27.
supplementation of uncooked corn starch both in day and
specifically at night. As the child grows into adol.escence, Nonalcoholic Fatty Liver Disease (NAFLD)
longer periods of fasting m ay be tolerated. Smee the This is a common cause of liver disease in children and is
metabolism of other carbohydrates also yield glucose-6- closely associated with obesity and insulin resistance. The
phosphatc, galactose and fructose also need to b_e prevalence is increasing with the expanding prevalence
restricted. Strict metabolic control with dietary therapy is of childhood obesity. NAFLD is a clinicopathological
the key to avoiding complications. diagnosis characterized by macrovesicular steatosis in
Type III glycoge11 storage disorder: There is a deficiency hepatocytes, in absence of other causes of chronic liver
of debranching enzyme manifesting as hepatosple~o disease. It ranges from simple steatosis (macrovesicular
megaly, hypoglycemia, fibrosis in the liver and elevation steatosis in hepatocytes without inflammation) to non-
alcoholic steatohepatitis (NASH, macrovesicular steatosis
in hepatocytes associated with inflanunation and fibrosis)
to cirrhosis of liver and hepatocellular carcinoma. Insulin
resistance and hyperinsulinemia is regarded as essential
to the disease mechanism. Hyperinsulinemia is a response
to energy dense diet (rich in saturated fats, sugars and
refined carbohydrates). This diet elicits hyperinsulinemia,
provides exogenous free fatty acids and drives the liver
towards lipogenesis.
Clinical presentation: Most children are asymptomatic.
Some have vague abdominal pain; examination shows
generalized obesity, cutaneous striae and ~ep~to~egaly.
Splenomegaly is uncommon. ~can~hos1s mgncai:s, a
velvety brown-to-black pigmen~ ms~ f~lds and axillae,
typically associated with hypermsulinenua can be found
in 30-50% patients.
Investigations: Typical biochemical abnormalitie.s in
NASH include moderately raised serum amm~
transferases (with ALT more raised than AST). Metabolic
abnormalities include hypertriglyce~idemia, ~levated
heeks In a child with
.
f tin rum insulin and hyperglycerma. Other disor~ers,
Fig. 12.30:Classical facles with chubbY c which se cause fatty liver can be elimin'ated on basis of
as g may
glyc0gen storage disease
Tttabnent: The fin:-t $~pin tn.'\ltit~ N:\FLD is t\l itfontif)'
it. Besides height .md wei~ht . w,\ist drcumft-rl'nce
provides highly infum\,ltin'.' "ht..l .md is ,, sum)~l\' for
Yisceral o~ity. The ln',ltmmt h,ls tW\' £'-)..\\~tt' rt'wn-e
lh-er di~J.se -lnd tt' rromi.'h:' ht\.1\thy gn"wth. Uh-style
changes ,1imed at \\~e~ht 1':'dul.'.'tion .rt~ t.':'-"t.'nti()\. Oit't,uy Sep.sis and S')·stemtc Infections
ch~ and incn:\.l~-d Fh~~k,,\ ,,cth·Hy lt.' \ld to diminished
insulin resistance ,lnd ,lf't' tlw nh1in st.1y 1.,)f ther,1py. Gr,"\m·p().<:itin' nnd gram-negntiv7 bacterial infecti.ons m.ay
Vitamin E has been shown t\) be :-.lfe and dft'CtiYe in result in jaundice. Up to one-third of neo~atal 1aundice
improving NASH hisrok1gy in childrt'n and its use is has bt't'n attributed to sepsis. The mechanism may vary
recommend~. Other m~'ik.ltil1ns likt' orlistat, metfonnin.. from imp~frrt'd cimaliculnr bile transport dt_ie to defective
UDCA and thiozolidin~iiones n:'1uirt' mt1re dnta to proYe trnnsptlrtcr poladzntion in hepntocytes without hepatic
efficacv. The role of b.ui,1trk sur~t.:'n· has not been necrosis to eleYntcd bilirubin load due to hernolysis in
establi~hed for childhood obesit\'. Pi-e,:l'ntion of over- clostridium infections nnd hepatocellular necrosis in
weight and obesity in children is the best strategy to pneumococcnl infections. Typhoid 1~ight result in elevated
o"-ercome the problem of NAFLD. nlkillinc phosphatnse, transammases nnd lactate
dehydrogcnase. Trnnsaminase elevation an~ liver dys-
Suggested Reading function is nlso present in dengue hemorrhagic fever and
• Barshop NJ, Sirlin CB. Sclmimmer JB, La\in~ JE. Re\'iew article: malaria.
t?pidern.iology, pathogt?n1?$iS and potential ~.ltml!lll$ of pt>dintric
non alcoholic fatty lin!r dise..l~. Aliment Phamulcol Ther 2008; lmmuno/og/cal Disorders
2S:l3-24.
• Mann JP, Goonetilleke R. McKidll..ln P. Pl-diatric non-alcoholic fattr Juvenile idiopilthic arthritis may be associated with
lh·er disease: a practical o\·erdew for non ::pt'Cinli::t. Arch Dis Child hepatomegn ly nnd elevated transaminases. Systemic
2015; 100:67'.r7. lupus erythematosus may be associated with hepato·
• Mitchel EB, La\ine JE. Re,·iew article: the management of pedintric megaly or autoimmune hepatitis. Transplacental transfer
non-alcoholic Ih·t?r dist?a:-e. Alinwnt Pharmacol Ther 2014; 40: of autoantibodies might lead to neonatal SLE with
1155-70.
transient cholestasis, congenital heart block, dermatitis
and hematological abnormalities.
Hepatic Manifestations of Systemic Diseases
Apart from disorders that directly involve the liver, a Hemolytic Anemias
number of disorders affecting other organ systems also
have hepatic manifestations. While, in some disorders, In thalassemia, the repeated transfusions and the increased
• these manifestations may be be.nign, in others the hepatic iron absorption due to ineffective erythropoiesis !rads to
chronic iron overload, fibrosis and cirrhosis. Recnrrent
• manifestations might significantly affect the outcome.
transfusions increase the risk of acquiring hepatitis Band
lschemlc Hepotiffs
hepatitis C infections. Sickle cell anemia has a similnr risk
of transfusion related hepatitis but more specific problems
Severe shock may lead to hypoperfusion of the liver. This are acute hepatic crisis which is a result of ischemic
shock may be the result of sepsis, acute cardiogenic shock insult. These individuals are also at higher risk of pigment
or severe intraoperative hypoperfusion as in cardiac stones resulting in acute and chronic cholecystitis. These
surgery. It usually manifests as an elevation of trans- episodes may be difficult to differentiate from acute
aminases to high levels. The degree of hepatic injury hepatic crisis.
depends on the duration and severity of shock. Thus,
coagulopathy as evidenced by prolonged prothrombin Malignancies
time and encephalopathy may result. Jaundice is a late
Leukemias and lymphomas might be associated with
manifestation.
hepatic infiltration, presenting as jaundice. Hemophago-
cytic lymphohistiocytosis, either familial or infection
Cardiac Disorders
induced, presents with fever, jaundice, hepatospleno·
Apart from an acute cardiogenic shock or intraoperative megaly, liver dysfunction and cytopenia. It is an important
hypoperfusion in cardiac surgery, liver involvement may differential diagnosis for liver failure in the first few
be seen as a result of congestion in right heart failure or as months of life. Sclerosing cholangitis may be a complica·
part of syndromes that involve both the liver and the heart. tion of Langerhans cell histiocytosis.
DI.eases of GastroJntHUnal System and Uver
~
eone Marrcw Transplant bile pigrnL"Jlt-5taiw.!d infl....>t.tina1 (."J'ithelial cells may be
conditionjng chemotherapy and total body irradiation mi~takl-n for pigrm.-nted ~tools. The prer ~ of pale stools
JtlaY lead to veno-occlusive disease manifesting as wf!ight docs not ru~riJy rc~i an extrahepatk or obstructive
gain,hepatom~galy, asdtcs and jaundice, Other ~UM~ of cause as many m.<.-1.alY>lk Jh-1a d i.5eaSl..!S wJth significant
uver dysfunction after bone marrnw transplant include liver dys function pre~ent ·1.t l th pale stools. Al&<>
intrahepatic diseau-~ with Y~ere paucity of bile ductul.es
graft versus h~~t disease (acute or chronic), sepsis ,
infections hepatitis and drug toxicity, or significant canallcular transporter d ysfunction may
prcrent with palt: ~tools. H(J'Never, pre--!>(~ of persistently
Endocrine Disorders pigrm-nt.ed
. yellow stools is not SC(."11 in biliary atresia. A
subsc.-t of patients pr~-*'Tlt w ith signs o f wagulopathy like
Uncontrolled diabetes meUitus presents with hepatomegaly skin or intracranial b1£:eds (seizures, irritability and
and fatty changes. Hypothyroidism manifests as jaundice bulging fontanel). Hepa t.omegaly or hepato-5plen~egaly
in the neonatal period predominantly due to impaired ls common. Early dec.ompensation is a feature in patients
conjugation ofbilirubin and partly due to decreased bile flow, with an underlying metabolic disorder. In a sick infant,
ce/fac Disease one should consider the diagnosis of galactosemia,
tyrosinemia, hemochromatosis, herpes and sepsis. Patients
Elevated transaminases may be observed, which with biliary atresia and choledochal cyst are otherv.•ise
normalize with gluten-free diet in the majority. Persistent healthy looking. Bil,ateral cataract and E. coli sepsis is
rise of transaminases should lead to evaluation for co- typical of galactosemia, whereas rash (maculopapular or
existing autoimmune liver disease. petechial), fe ver, chorioretinitis, microcephaly and
lethargy are suggestive of congenital infections.Triangular
NEONATAL CHOLESTASIS fades, pointed chin, prominent ears, cardiac murmurs and
butterfly vertebrae are seen in Alagille syndrome.
Jaundice is common in neonates as physiologkal jaundice Splenohepatomegaly w ith cherry-red spot on fundus
is found in a majority. This jaundice usually resolves by examination suggests storage disorder.
two weeks of age. Also, most pathological causes of
unconjugated jaundice are detected and treated by two Diagnosis
weeks of age. Though breast milk jaundice can be a cause Neonatal cholestasis has a multifactorial etiology
of unconjugated hyperbilirubinemia beyond two weeks (Table 12.36). The etiological spectrum in referral western
of age, cholestatic jaundice is an important and potentially centres is as follO\\'s-biliary atresia (25%), PFIC, Alagille
serious condition that needs evaluation and early syndrome and bile acid synthetic di sorders (25".;,),
treatment. Conjugated hyperbilirubinemia is defined as metabolic (20%), idiopathic neonatal hepatitis ~TH, 15%),
direct bilirubin value greater than 1 mg/ dL if the total alpha-1-antitrypsin deficiency (10%), and \·iral (5%). nus
bilirubin is less than 5 mg/ dL, or a value of direct bilirubin data is relevant as the proportion of cases with Il\.TH
that represents more than 20% of the total bilirubin, if the reduces when all necessary investigations especialk
total bilirubin is >5 mg/ dL. Conjugated hyperbilirubinemia metabolic tests are done. Also, it warrants mention ~t
presents with high colored urine staining the diapers this is a western data and that alpha-1-antitrypsin is not
unlike unconjugated hyperbilirubinemia. All newborns as prevalent in India as in European countries. Liver
having jaundice beyond 14 days of age with dark-colored dysfunction, general condition and stool color are
urine with or without acholic stools should be referred to important features in the differential diagnosis. These
tertiary health facilities for further investigations and infants need a detailed investigative workup b ased on a
treatment without loss of time after a dose of vitamin K rational approach so as to avoid unnecessarv and costlv
injection. The need for time bound early evaluation and investigations. The etiology and algorithm of evaluatio~
treatment is manifold as mortality and poor outcomes are is different in a 'sick' and 'not sick' infant with cholestasis
common in children with metabolic liver diseases and as shown in the flowchart (Fig. 12.31). This approach
biliary atresia respectively when the ref~rral is de~ayed. avoids a battery approach to investigations.
Often, valuable time is lost by work-up m less eqwpped
In a non-sick infant witlr pale stools, the main objective
Primary health centres.
is to quickly establish the diagnosis or rule out biliarv
atresia. Liver biopsy is an accurate (90-95%) test f~r
C//n/ca/ Features differentiating biliary atresia from other causes of neonatal
Neonatal cholestasis is characterized by high colored urine cholestasis. In biliary atresia, portal tract expansion,
along with jaundice. Jaundice is seldom. no~ced ?Y ~e ductular proliferation and fibrosis is seen, whereas in
parents in the eyes as the sclera is not easily v1~ua_hzed m neonatal h epatitis, there is alteration in lobular
them. Referral of children with biliary atres1a is often architecture, focal hepatocellular necrosis and giant cells
de~ayed as they are healthy looking and ga~g weigh.t. formation. Priming with UDCA or phenobarbitone for 3
~allure to thrive is common in children with met~bolic days before HIDA scan improves the diagnostic efficacy
lVer diseases. Stool color is best assessed by looking at of HIDA. HIDA is more relevant for its negative predictive
the core of the stools as otherwise pale stools covered by value (100%) as the presence of excretion into gut rules
_326, Essential Pediatrics
_..,_.....
-· Table -fa.36: Causes of neonatal cholestasls
&traheps.tic cfsorders lntrahepatic disorders
8itis.ry atresia'" Metabolic: Galactosemla", tyroslnemla*,
Choledochal cyst• Progressive familial lntrahepatlc cholestasis (PFIC 1 and 2)*, Niemann-Pick type c
ln:spissated bile duct syndrome• disease, mitochondrial hepatopathy and fatty acid oxidation defects*, bile acid synthetic
Spontaneous perforation of bile duct defect, Zellweger syndrome,
Wolman disease, cystic fibrosis, alpha-1-antitrypsin deficiency, hereditary fructose
intolerance
Infection: Sepsis*, urinary tract Infection•, TORCH
Idiopathic: Neonatal hepatitis •
Genetic: Alagille syndrome•, Down syndrome, Trisomy E
Endocrine: Hypopituitarism, hypothyroidism
Anatomic: Congenital hepatic fibrosis, Caroli disease
Others: Neonatal hemachromatosis, total parenteral nutrition related, multifactorial
cholestasis of prematurity*
"Common causes
I
Jaundice >2 weeks of life
High colored urine
:I
...
l Direct bilirubin >20% of total bilirubin I
Neonatal cholestasls
...
Injection vitamin K
I
...
I Sick Oethargic, ascites, encephalopathy, coagulopathy, hypoglycemia, I
seizures, edema), failure to thrive
I
Yes
i No
Possibilities IPale stools, to be seen by physician J
Galactosemia, tyrosinemia,
neonatal hemochromatosis
Sepsis, urinary tract infection
I
Congenital intrauterine infections No Yes
Herpes infection, congenital malaria
Hemophagocytic lymphohistiocytosis Possibilities Possibilities
Hypopituitarism Progressive familial intrahepatic cholestasis Biliary atresia
Paucity of intrahepatic bile ducts Choledochal cyst
Cystic fibrosis lnspissated bile duct syndrome
Bile acid synthetic defects Caroli disease
Alpha-1-antitrypsin deficiency Sclerosing cholangitis
I Workup as per likely cause I Wolman's disease, Niemann-Pick type
Idiopathic neonatal hepatitis
c
Ultrasound abdomen
Choledochal cyst
Biliary atresia
lntrahepatic biliary radical dilatation
T
,, i
Serum gamma-glutamyl transpeptidase
Liver biopsy
Further workup as per likely cause
i l '
m
hepatic cholestasis types I and II, tyrosinemia, mito- iv. Bacterial sepsis: Intravenous antibiotics
chondrial cytopathies and bile acid synthesis defects, etc. v. Toxoplasmosis: Pyrimethamine and sulfadiazine with
Management folinic acid
vi. Galactosemia: Lactose free diet
Delayed diagnosis leads to problems of undemutrition, vii.Hemochromatosis: IV immunoglobulins (!VIG) with
coagulopathy, pruritus (older infants), portal hyper- exchange trCl.'.lsfusion may be useful
- . - -
Table 12.37: Multivitamin supplements for cholestasls
·orug Dose Side effects
Vitamin K 2-5 mg IM, repeated monthly Overdose may lead to hemolysis
Oral: 2.5-5 mg alternate day
·Vitamin o Vitamin 0 3 : Oral 1000-2000 IU/day Monitor for hypercalcemia, nephrocalcinosis
or 30000 IU q monthly
Vitamin E Aquasol E: 5Q-400 IU/day Pseudotumor cerebri, hepatotoxicity, hypercalcemia
Vitamin A Aquasol A: 2500-5000 IU/day Pseudotumor cerebri, bone pains
Injectable 30,000 IU/IM at diagnosis and
1o,ooo IU/IM monthly till cholestasis resolves
Water-soluble vitamins Twice the RDA None
IM: Intramuscular; RDA: R~commended daily allowance. . .
Doses are provided as a recommended guide and need to be adjusted as per clinical scenario, response and vitamin levels.
111111 328 I ~~~~~----~~~~=E~••=o~nt~la~l~P~ed~la~tr~lo=•:...---~------------------.
There is considerable delay In reform) of pnlfonlB with 11Rpllt Bmft (lcdt J.attmtl graft nr IP.ft lnb~) fr1 1m .a fhJ
donor. Auxiliary Jlvor lran1>plantstUon i:; aMtJll!r rM,,~~
------
neonatal cholestasis to higher ccntcrA In Jndln. ThlH rcaultR
in delayed etiologic diagnosiA, mlA:-;cd opportunity for where nallvc liver ffi not remow!d tintJ a Hw·r r,rMt 1
corrective biliary atresia surgery In first 60 duyH nnd 11.ver the donor JH Hurglcally pla~d Jn addJtfon fl> thi~ ,/~~ii
. l N ,, "·11•
decompensation in patients with metobolic etiology. Thua liver. Thltf ll-1 uriually d onJJ (or C"~ ~,.. aw1r typed fJ/f.fJJ+~
all efforts should be targeted townrdA early ldcntlflcatlon liver follurc.
of neonates with conjugated hyperbilirublncmln and their The main fndlcaHonRft,, liver tranr;plant.atfon ambilfar·
referral to centres with expertise. atrcala, fulmlnant hepatic fallure and chmnkliv~rrli~-?~
secondary to multiple caur«?H and h<~paHc tum1.>r1i,urJ..f~A
Suggested Reading selection of a blood group compatlbl1: dt>nori.Hv:r.1,, M,
including detailed evaluation of li ver funr.tinnf! awJ y)~J
• Guideline for the cvnluntlon of cholcstntlc Jnundlrc In lnfont11:
Recommendations of the North American Society for Pediatric serologies. The rcclpicneHdiHCilfR..d 111/(! f J,, mrlllm~ .?rl'j
Gnstroenterology, Hepntology nnd Nutrition. J Pcdlatr the new Jlver l8 trnn'1plant.cd, c.m,;uring va8c.ufar and IJ.ilfary
Gastroenterol Nutr 2004; 39:115-28. anastomoRitJ. PatlcntB rnqufre lifclonf) lmm1JntJ,
• Roberts EA. Neonatal hepatitis syndrome. Scmln Nconntol 2003; supprer;sion Ut-Jing corticot~tcroid s, tacrnlim1Js ~M
8:357-74 mycophcnolatc mofotil initially and lat<!r. maintt~fllJr.r>.
• Bhatin V, Bavdekar A, Matthai J, Walkar Y, Slbnl A. Mnnngcmcnt
of neonatal cholestasis: consensus stntcmcnt of the Pediatric
therapy with tacrolimus. Rejection and infc.cti"n am rn;;y-,.
Gastroenterology chapter of Indian Academy of Pediatrics. Ind complications following trnm;plantation. Five-year patitf~
Pediatr 2014; 51: 203-10. survival rate exceeds 80'%.
Hematopoiesis ANEMIA
The hemangioblast is the stem cell from which endothelial Anemia is a sign, it is important to investigate the cause
and hematopoietic cells develop. Stem cells that give rise of anemia to ensure that it is not due to a serious
to only blood cells are called hematopoietic stem cells.
underlying ailment and to define the correct management
They give rise to two colony-forming units (CFU), one is approach.
the common myeloid precursor: Granulocy tes, erythro-
cytes, monocytes and megakaryocytes, also termed CFU- Definition
GEMM. The second is the common lymphoid precursor,
dedicated to the production of lymphocytes and called Anemia is present when the hemoglobin level in the blood
CFU-L. The CFU-GEMM gives rise to two progenitors, is two standard deviations below the mean for the
specific for both the erythrocyte and the megakaryocyte particular age and sex (Tables 13.1, 13.2). The physiologic
(CFU-EMk), and another for granulocytes and monocytes definition of anemia is a condition in which tissue hypoxia
(CFU-GMo). Each of these develops into specific lineages, occurs due to inadequate oxygen carrying capacity of
the CFU-GMo gives rise to four lineage-specific CFUs, blood. According to the National Family Health Survey
three dedicated to each of the granulocyte lineages (CFU- {NFHS-4) data, the incidence of anemia in urban children
Eo for eosinophils, CFU-N for neutrophils and CFU-Baso is 55.9%, rural is 59.4% and overall is 58.4%.
for basophils) and CFU-Mo that is specific for monocytes.
The CFU-L gives rise directly to three lymphoid cells: B Physiological Adaptations
lymphocytes, T lymphocytes and natural killer cells. This Anemia leads to decreased oxygen-carrying capacity of
complex and sequential development of hematopoietic the blood and compensatory physiological adjustments.
cells is driven and regulated by local growth factors and Tissue hypoxia develops when the enhanced release of
cytokines. oxygen from hemoglobin and increase of blood flow to
\:t" ,..__ ..... . , .. .. ,,_ .. .... - _,, . -· ...
Table 13.1: Hemoglobin and hematocrit in infancy and childhood
Hemoglobin (gldL) Hematocrit (%)
Age Mean -2SD Mean -2SD
Birth _(cord blood) 16.5 13.5 51 42
, 1-3 days (capillary) 18.5 14.5 56 45
1 Week 17.5 13.5 54 42
_2 weeks 16.5 12.5 51 39
~month 14.0 10.0 43 31
"2months 11.5 9.0 35 28
3-6 months 11.5 9.5 35 29
o.S-2 years 12.0 10.5 36 33
:2--6 years 12.5 11.5 37 34
~-~12 years 13.5 11 .5 40 35
G·•rls 12-18 years 14.0 12.0 41 36
: ~ 12-18 years 14.5 . .. 13.0 43 37
'laJues two. standard deviations bel~w the mean (-2 SD) indicate the lower limit of normal
329
sso 1
Teble 13.2: Cutoffs tor hemogiobln and hematocrlt proposed Approach to Diagnosis
by tho World Health Organization to define anemia The history may give clues for the etio~ogy o.f anemia. ~ere
Ago group Hemoglobin (g/dL) Hematocrit % may be obstetric history of maternal infections, anenua or
Children, 6 mo to 5 years <11 .0 <33 collagen vascular diseases, or presence ~f prema~ty,
Chlldren, 5-11 years <11.5 <34 blood loss, jaundice [secondary to ABO or Rh incompatibility,
Children, 12-13 years
glucose-6-phosphate dehydrogenase (G6PD) de~ciency
<12.0 <36
d sis] hemangioma or cephalhematoma. History is
Non·prognant women <12.0 <36 an sep ' d tity f milk .
taken regarding the diet, type an quan . ~ , time of
Men <13.0 <39 weaning and intake of vitamins and hematinics. Nutritional
Sourco: WHO 1997 iron deficiency anemia often oc~urs betw~en. 6 months and
2 years due to inadequate wearung, chrome diarrhea or cow
the tissues is insufficient to meet requirements. The milk allergy. Adolescent gro~th spu:t~ menstruating and
mnintcnnnce of blood volume occurs by an increase in the pregnant teens are at risk for iron defiaei:cy. A vegetarian
volume of plasma and redistribution of blood flow . diet and use of goat milk may result m megaloblastic
Cardiac output increases in anemia as a consequence of anemia. History of pica, drug intake, chronic diarrhea, prior
increased stroke volume, this high output state increases surgery, acute and prolonged infections, liver and renal
oxygen delivery to tissues by increasing the flow of blood. disease, transfusions and age of onset of symptoms should
Diversion of blood flow occurs from tissues with lesser be taken. Thalassemia major usually presents at 4--6 months
oxygen requirements to those with greater needs. Thus of age, and 70% present with symptoms by one-year.
skin blood flow is reduced, while cerebral and muscle Diamond-Blackfan (pure red cell) anemia, usually presents
blood flow are increased. at 3-month or earlier and shows a consistently low
reticulocyte count and absence of erythroid precursors in
Cllnlcal Features the marrow. Fanconi anemia has a variable and later onset,
The hemoglobin level at which symptoms of anemia with children presenting at 3-4 years of age or even in
develop depends on two factors, the rate of development adulthood. A family history of anemia, gallstones and
of anemia and state of the cardiovascular system. In requirement for blood transfusions may suggest the
general, symptoms occur at a higher hemoglobin level diagnosis of chronic hemolytic anemia, including hereditary
with rapidly developing anemia, e.g. due to acute spherocytosis or G6PD deficiency.
hemorrhage. Examination is done for clues to the cause of anemia,
Tiredness, lassitude, easy fatigability and generalized e.g. radial limb anomalies (bone marrow failure),
muscular weakness are most frequent and the earliest splenomegaly (hemolytic anemia, infection, storage
symptoms of anemia. This presents as poor feeding, diseases), and lymphadenopathy and hepatosplenomegaly
irritability and inadequate school performance; pallor is (malignancies, malaria, tuberculosis). Petechia, purpura,
the most prominent and characteristic sign. Pallor of nail icterus and bossing also help to diagnose the cause.
beds, oral mucous membranes and conjunctivae are Laboratory Investigation
reliable indicators of anemia. Dyspnea on exertion,
tachycardia and palpitation are common symptoms. It is important to know the age and detailed history of the
child, this information will provide direction to the
Hemic murmurs become prominent with severity of
laboratory investigation. The complete hemogram will
anemia. These are midsystolic flow murmurs, reflecting
reveal, if there is isolated anemia, or if other cell Un.es are
increased velocity of blood passing through the valves.
affected. The red cell indices will demonstrate the type of
They are heard in the pulmonary area, but can be heard
anemia; while the mean corpuscular volume (MCV)
in areas corresponding to any of the heart valves. Systolic
denotes the size of the red cells, the mean corpuscular
bruits, postural hypotension and congestive heart failure
hemoglobin (MCH) and mean corpuscular hemoglobin
may be seen in patients with moderate to severe anemia. content (MCHC) provide information on red cell
Nervous system symptoms include dizziness, headache, hemoglob~z~tio~ (Table 13.3). Using the MCV, a..nemi~s
humming in ears, fainting, tinnitus, lack of concentration can be class1f1ed into microcytic/normocytic/macrocytic
and drowsiness; with severe anemia, clouding of anemia (Figs 13.1-13.3). Abnormal red cell indices can exist
consciousness may occur. in subjects even when the underlying disorder is not
Severe anemia is characterized by a high output state sufficiently severe to cause anemia. In thalassemia minor
with elevated pulse pressure and a 'collapsing' character. or iron deficiency, the MCV, MCH and MCHC are Jo\V
Electrocardiographic changes may be found in approxi- and in megaloblastosis, the MCV is elevated. The red cell
mately 30% of patients with hemoglobin of less than distribution width (ROW) gives the size difference in the
6 g/dL. Findings on ECG are normal QR~ wav.es, red blood cells, low ROW means all the red blood cells
depression of the ST segments, and flattening or inversion are small and uniform in size, while a large RDW shows
of Twaves. that the cells vary in size greatly. Examination of the
_.,,.,.-- _Homntol~glonl Dliordor•
-""- ----'pO;=----~-
I 331
(ifdcell fndic6s Tablt 13.~t Red oall lndloH nnd 11orum lroti AIUdlna In normt1I ohllclrnn
1Jlrtl1 O.tJ-2 yr 0-12 yr Qlrlt1, f2,,.10 yr BoytJ, 1~18 yr
~n corpusculnr volume (fl)
100 70 00 00 88
Mesn corpusculnr hemoglobin (pg) 34 iJ()
27 20 00
Me.'n corpuscular hemoglobin conco"tmtlon (g/dL) 33 33 34 34 M
Red cell distribution width (ROW)" 12,8-±1.2%
setUm Iron
eo..110 µg/dt. (1 o-30 µmol/L)
,serum "'rritln, medlan (range)
1a
1O0 (16-300) ng/mL (boyn); 40 (15-200) ng/mL (glrto)
l lbtal Iron binding capaclt
i
"(lansferrin saturation-- Y 260-400 µg/dL (47-70 pmol/L)
I
L~ -- · · . 20-50%
•ROW • st-andard deviation (SD) of rod bl d · · '
1
••Transferrin saturation • oo coll volumo >< 100/rnoon corpuoculor volumo.
Sorum Iron >< 100/totnl Iron binding cnpuclly
- Low
- serum Iron- . . i
Low ferritln
lnen)ssed total Iron
binding capacity
Normal or lncroosod sorum Iron
N0<mnl or low totol "o"
cap:r~ on~~~:rltln
l -•
Homoalobln HPLC or fJlcctrophore?.is 1
I
l
binding -· - - ..
Homoglobln
[ oloctrophorosls or HPLC
I Homogloblnopathy
homoglobln SS,
- --1 - S-C, B·n thalauemla I
~eflciency .~~-'-~~~~~~~~+
Abnormal Normal
- - - ---,
C-reactive protein
-
Elevated Normal
•
Inflammatory
disease
Anemia of
chronic dlaease
Fig. 13.1: Approach to mlcrocytlc anemia. HPLC high performance liquid chromatography
J>eripheral smear will reveal the red cell morphology, Table 13.4: Retlculocyte count In evaluation of ane~ia · '
Presence of schistocytes, polychromasia, specific red cell Low retlculocyte count
~orphology or parasites may help in makin~ th.e Congenital or acquired, aplastic or hypoplastic anemia
diagnosis. The reticulocyte count helps to determine if Transient eythroblastopenla of childhood
anemia is caused by red cell destruction or decreased Pure red cell aplasla
production, the corrected or absolute reticulocyte count Parvovirus 819 infection
IS more useful (Table 13.4). When nutritional anemias are Bone marrow Infiltration by malignancy, storage disorder
SUspected, iron status, vitamin B12 and folic acid levels High retlculocyte count
~e determined. The reticulocyte count is. decreased in Hemolysls: Autoimmune hemolytic anemia, hereditary
one marrow failure syndromes, transient erythro- spherocytosls
blastopenia of infancy and infections, e.g. parvovirus. In Hemorrhage
cases of anemia with increased reticulocyte count, a Splenic sequestration
Recovery from vitamin 8 12, folic acid or iron deficiency
Coombs test will help to identify, if this is due to immune
Sepsis
or hereditary hemolytic anemia.
332
Nonnal or reduced
\seru~
I
+ + Yes No
Low Nonna! or high
l
Anemia of chronic disease
Early Iron deficiency
Negative
!
~~~~__lL-~~~~~~~~--~::--:-~
Positive
Anemia of renal,
IM;
H
endocrine disease
lytlc anemia
~~o _ _ _ _ _
hepatic~
·
_I L
Hemorrhage
Recovery from nutritional
deficiency or sepals
-~utolmm:~.----
hemolytic anemia,
thalassemla
-
Macrocytosls
Yes No
+
I Megaloblastlc anemia likely I
+
Levels of vitamin B12 and folic acid Reticulocyte count
(or response to therapy)
Bone marrow examination
+ +
Low levels or anemia No megaloblastlc changes In Decreased Increased
improves with therapy; marrow or no improvement
megaloblastic changes with therapy -t
in bone marrow Liver function tests, Hemolysls \
thyroid hormone Hemorrhage
- -i
+
Abnormal •..
Normal
-
tto
JR()N DEFICIENCY ANEMIA
Paf'hophysiology
!)inrinished dietary iron absorption in the proximal small
intestine or excessive loss of bod'"" iron can ~-ult in iron
deficiency. Iron is essential f~r multiole metabolic
processes, including oxygen tran:.--port, D::'-L.\ ~thesis, Ag. 13.4: Peripheral smear from a child with iron deficiency
and electron transport. In se\ere iron deficien"c,, iron- anemia. shows microcytosis (the red blood cells are smaller
then the small lymphocyte in the field), hypochromio (central
containing enzymes are lmv and can affect imm~e and
poUor > 1/3rd of cell diameter), thrombocytosls, and o few
tissue function. Iron defidencv anemia can result in ovorocytes and tear drop cells (moderate onisopoildlocytosls).
diminished growth and leantlng and have serious Jenner-Giemsa xlOOO
consequences in children. Dietary constituents, e.g.
phytates, phosphates and tannates, ma_'lce non-heme iron increased. Serum iron is reduced, total iron binding
unabsorbable. capacity (TIBC) is increased and transferrin is reduced to
Healthy newborn infants ha\""e a total body iron of less than 16% {normal 25-50%). The reduction in serum
250 mg (-80 parts per million, ppm) that decreases to -60 ferritin occurs early, and correlates with total body iron
ppm in the first 6 months of life. Body iron is regulated stores. Ferritin, an acute phase reactant, is elevated in
carefully by absorpti,·e cells in the proximal small inflammatory conditions, and may thus be falsely high in
intestine, which alter iron absorption to match body losses a sick child. High free erythroprotoporphyrin (FEP) is seen
of iron. Breast milk iron content is more bioa'\"ailable than before anemia develops.
cow milk. Besides this fact, infants who consume cow milk
have more iron defidencv because bo\""ine milk has a Treatment
higher concentration of calctum, which competes '"ith iron The cause of anemia should be identified and corrected.
for absorption and they may haYe gastrointestinal blood Hookworm infestation is the commonest cause of occult
loss due to milk allergy. Intercurrent infections and gastrointestinal blood loss in rural India at all ages. Dietary
infestations compound the problem. counseling and treatment of any other causative factors
are required to prevent recurrence or failure of therapy.
Clinlcal Evaluation Oose follow-up is required to assess for adequate response
Dietary history is important, including intake of ~, and correction of anemia, this will help to identify iron
Weaning foods and supplements. Pica increases the nsk therapy failure (Table 13.5).
of infestations and lead paisoning. Common_ features of
anemia are present in proportion to the seventr
~d ~te
of development. Behavioral symptoms,_such as rrntability
and anorexia, precede weakness, fatigue, leg crai:nps,
breathlessness and tachycardia. Congestive heart ~allure
Oral iron preparations should be taken on an empty
stomach or in between meals for best absorption. About
parenteral dose every 3-12 months). . I 1c1crut:1 (hcrcdllnry 11p 1croc yt11~1~)
gal I atonca 111H (ll I I · ·'
hemol tlc/thnl111:11:1c111lc foe 1Ct! 111 flllllt'lll 11 rri 11 )1J1,
Suggested Reading Y:ll ·)(l1llJ' ·•36) I Je1.1ulccni(1:1lcklc<.:dltllt.t<lfit·) cnti
l lllt:!l'lllCC ll l1' J ' l1
• Devalia V, Hamilton MS, Molley AM. Guidelines for the d!ngnosls help lund lnvc1:1tlg11llont1i co11(lrmntnry tcrjlu ilrc t llll
and treatment of cobalamin and folate disorders. Dr J1-foemnlology
2014; 166:496--513.
required.
Laboratory Manlfosfatlonn
HEMOLYTIC ANEMIAS
- - - - - - - -- - - --- - - - - - - -- Lnborntory findings Jn hcmolyllc ancmln nrc: (I) lncrn;w:d
The term 'hemolytic anemia' is limited to conditions in erythrocyte dctilrucllon (Table 13.9,>, (JI) co~p1:n11ti!r1ry
which rate of red cell destruction is accelerated and ability increase In erythropolc1:1l1:1(Tobie13.10), and (Iii) fr·at un~
of the bone marrow to respond to the anemia is specific to pnrticular hemolytic anemia. /\n clcvat1:1J
unimpaired. Table 13.8 lists important causes. Under corrected rcticulocytc count may be the only fc:iturc vf
maximal stimulation, the normal marrow is capable of mild hemolytic nnemin. The Coomb1:1 lcfll lfl tlw rrM 1
increasing its production about 6-8 times its basal level.
The reticulocyte count is useful in determining the rate of
red cell destruction. The normal reticulocyte count value
in the newborn is 3.2+1.4% and in children 1.2+0.7%.
I -
1 Table 13.8: Causes of hemolytlc anemia
Acquired
Mechanical: Macroangiopathic (artificlal heart valves, march
hemoglobinuria); microangiopathic (disseminated lntravascular
coagulation, hemolytic uremic syndrome, thrombotic thrombo-
cytopenic purpura)
Infections: Malaria, kala-azar, C/ostridium welchii
Antibody mediated: Autoimmune hemolytic anemia (warm and
cold types)
Transfusion reactions: Immediate and delayed
Hemolytic disease of the newborn
Drugs: Cefotetan, ceftriaxone
Hypersplenism ,
Cryopathy, e.g. cold agglutinin disease, paroxysmal cold
hemoglobinuria Fig. 13.6: Chlld with hemolytic anemia, showing homoty11C
facles and lcterus
Physical injury, e.g. burns
Chemical injury. Snake bite, lead and arsenic toxicity
Table 13.9: Laboratory signs of accelerated
:inherited erythrocyte destruction
Hemoglobinopathles, e.g. thalassemia, sickle cell disease Fall In blood hemoglobin level at >1.0 g/dL per week
Red cell membrane defect, e.g. glucose-6-phosphate dehydro- Increased serum level of unconjugated blllrubln
genase deficiency
Increased urinary uroblllnogen excretion
Disorders of the cytoskeletal membrane, e.g. hereditary
spherocytosis Increased serum lactate dehydrogenase
Unstable hemoglobins Reduced haptoglobln and hemopexln
Lipid membrane defects, e.g. abetalipoprotelnemla Reduced glycosylated hemoglobin
Porphyria Decreased erythrocyte lifespan (using radioisotope 51 Cr)
I 331
f;tllt 13.fo: Laboratory signs Of aceelerated efythrOPoiesis Hemolytic disorders may be divided into inherited and
'~ralblood
acquired varieties. This classification has a pathogenetic
~romasia or reticulocytosis significance because the nature of hereditary lesions differs
~osls from those acquired. Most intrinsic defects are inherited
~ease in nucleated red cells and the extrinsic are acquired. There are a fow exceptions
I.
n
acute self-limited disease (<3 months). Thalassemia should be considered in any child with
hypochromic, microcytic anemia that does not respond
Suggested Reading to iron supplementation. Children with thalassemia major
usually demonstrate no symptoms until about~ months
• Choudhry VP, Seth T, Saxena R. Hemolytic anemias. deGruchy
Oinical Hematology in Medical Practice. Wiley India (6th edn)
of age (when chains are needed to pair with chains to 1
2013; pp 146-18.3. form HbA, after chains production is turned off). The
• Gupta N, Sharma S, Seth T, et al. Rituximab in steroid refractory condition may not be recognized because of the delay in
autoimmune hemolytic anemia. Indian J Pediatr 2012; 79: 803-805. cessation of HbF production till 3-5 years of age in some
cases. Severe pallor and hepatosplenomegaly are almost
THAl.ASSEMIAS always present. Icterus is usually not seen but mild to
Thalassemia is a Greek term derived from tlialassa, which moderate jaundice may be found due to liver dysfunction
means "the sea" (Mediterranean sea) and emia, which from iron overload and chronic hepatitis.
means "related to blood". It occurs due to globin gene Features of severe anemia, including intolerance to
defects, one of the commonest monogenic diseases. exercise, irritability, murmur or signs of heart failure may
Molecular biology and genetics of thalassentla syndromes be present. Bony abnormalities, such as frontal bossing,
have revealed more than 200 mutations, across prominent facial bones and dental malocclusion are
populations from Southeast Asia to Africa. Carrier rates usually present (Fig. 13.6). Ineffective erythropoiesis
f~r thalassemia reported in North Indians, varies in creates a hypermetabolic state associated \\Tith fever and
different ethnic groups from 3-17%. failure to thrive. Hyperuricemia may be present.
Spie.ctrun'\ of ~ Tholossemlas
~ fJ:i41A~>:t'mia trait: PaHcnts have mild anemia and
~bn('n"i'l,!!1 ~d <-dl indkes; high performance liquid
ch'r\'-.mAti..)£Taphy (HPLC) or he1noglobin electrophoresis
~ho,,'5 ~kYAk'd k\'ds ot HbA2 or HbF, or both. Peripheral
b11.)1.)d film. ('Xan'\in<Hion shows marked hypochromia,
micrc,. . .ytosk> (\,ithout anisocytosis, which is found with
iron dc-nci~~y) ~md t.n~t cells.
laboratory Studies
Complete blood count and peripheral blood film results
are sufficient to suspect the diagnosis. In thalassemia major
and intermedia, the hemoglobin level ranges from 2-8 g/ dL;
MCV and MCH are significantly low. Reticulocyte count
is elevated to 5-8% and leukocytosis is usually present. A
shift to the left is also encountered, reflecting the hemo..
lytic process. The platelet cormt is usually nor?'al, unless
the spleen is markedly enlarged and causmg hyper-
splenism. .
Peripheral blood film reveals hypochromasia and
microcytosis, polychromatophilia, nud.eated _red blood
cells, basophilic stippling and occasional immature
leukocytes (Figs 13.7 and 13.8). An HPLC sample i:nust be
sent prior to the first blood transfusion to confirm the
~ ~ . ~ent wftll
diagnosis of thalassemia that shows absence of ~A. and Fig. 13.8: Peripheral smear from an asymptomatic J-JV" rnio.
high levels of HbF. Elevated HbA2 is characteristic of hemoglobin E disease. showing mlcrocytosls, hypoctiro cx;o
thalassemia trait. target cells and nucleated red blood cells. Jenner-G1ernsa x1
Hematologlcal Disorders I a41 -
--
342
- I E11ontlal Padlatrlc1
l.tJborufory DfucJJa;
I l1ttt1nl11ftJr,lcill fcatun:s of rMtru-11 failure include single
cyf1JJ1!.!tlln, at; In pure red cell apfosia and amegakaryocytk
Special Tests
.. re
Fig. 13.9: Child with Fonconl anemia. The child hod hyper- The Ham test or sucrose hemolysis test may be posttl\.
plQrnenfCJllOn, mlcrocopholy and mlcrophtholmla. She also hod in patients with paroxysmal nochimal hemoglobinurt~
radial roy cJotocto and growth retardation (red cells lysed by patient acidified sera) and type
Hematologlcet Disorders I 345
IPancytopenla] Prognosis
f Severe anemia can result in high-output cardiac failure/
Peripheral blood smear, retlculocyto count, ncutropcnia can lead to bacterial and fungal infections;
red cell Indices, Indirect blllrubln
severe bleeding can occur due to thrnmbocytopenia. The
severity and extent of cytopenia determine prognosis.
Reduced retlculocyte Hemolysls or With current HSCT regimens, mo~t patients with severe
count, normal Indirect retlculocytosls aplastic anemia show 60-70% Jong-term survival; better
blllrubln, no evidence survival is reported in favorable subgroups.
of hemolysls
Suggested Reading
Deficiency of vitamin 8 12, folate Sepals • Mahapatra M, Singh PK, Agarwal M, l:t al. Epidemiology, clinical
Bone marrow fallure, fibrosis Hypersplenlsm and hematological profile and managfmlE.'flt of apl.as tic anemia;
Bone marrow lnflltratlon Paroxysmal AJIMS experience. JAPl 2015; 63: 30-35.
Storage disorders (Gaucher) nocturnal
hemogloblnurla
HEMATOPOIETIC STEM CELL TRANSPLANTATION
Fig. 13.11: Algorithm for evaluation of pancytopenla Bone marrow transplantation (BMT) is more correctly
called hematopoietic stem cell transplantation (HSCI).
congenital dyserythropoietic anemia (red cells lyscd by This is an established life-saving procedure for a number
other acidified sera but not patient sera). A recent of malignant and non-malignant diseases. The
transfusion with packed red cells may induce a false- hematopoietic stem cell transplants are of the following
negative test result. A specific test for paroxysmal types: (1) Autologous transplant-when the source of stem
nocturnal hemoglobinuria is assay for two complement cells is harvested from the patient and (2) Allogenek
regulatory proteins normally present on red cells, CD55 transplant-when stem cells are collected from a human
(decay accelerating factor, OAF) and CD59 (membrane leukocyte antigen (HLA) matched sibling or unrelated
inhibitor of reactive lysis, MIRL). Deficiency of CD55/59 donor. The commonly used sources of hematopoietic stem
on red cells is the hallmark of the disease. Peripheral blood cells are cytokine mobilized peripheral blood, bone
cells in Fanconi anemia show characteristic hyper- marrow and umbilical cord blood.
sensitivity and chromosomal breakage with cross-linking Indications
agents (mitomycin C and diepoxybutane). The chromosomal
fragility is seen even in patients who lack physical stigmata The indications for hematopoietic stem cell transplantation
of the disease. can be conveniently divided into two groups (Table 13.13):
(a) Malignant disorders-here the cure is by the high doses
of chemotherapy or radiation therapy, while the transplant
Treatment
serves to rescue the patient from the myelotoxic effects of
Supportive care such as packed red cells for anemia, the anti-cancer therapy. In allogeneic type of transplants,
platelets for thrombocytopenia and antibiotics for infection there is an additional benefit of the immunological
is needed. Hematopoietic stem cell transplant (HSCT) is response of 'graft versus cancer effect', which contributes
the only curative therapy. Criteria for referral for HSCT to controlling the disease. (b) Non-malignant diseases-
is: (i) patients who are young, (ii) severe aplastic anemia, in these conditions the abnormal marrow is destroyed and
and (iii) a matched related sibling donor. Patients with replaced by the healthy unaffected donor marrow. This
severe acquired aplastic anemia who cannot undergo I. • ~ • - - - - ' -· . . . . - - .•
HSCT may benefit from therapy with antithymocyte Table 13.13: Indications for stem cell transplantation '
globulin (ATG) or anti-lymphocyte globulin (ALG) and Malignant disorders ' Non-malignant disorders '
cyclosporine. Granulocyte colony-stimulating factor (G- Acute myeloid leukemia Thalassemia
CSF) is indicated in patients with neutropenia with Chronic myeloid leukemia Aplastic anemia
infection. If the neutrophil count does not increase, this Acute lymphoblastic leukemia Fanconi anemia
therapy should be discontinued after 7 days, because of (high risk) Immunodeficiency syndromes
the risk of malignancy. Hodgkin disease Inborn errors of metabolism
Therapy with ATG or cyclosporine is contraindicated Non-Hodgkin lymphoma Autoimmune diseases (rare)
in patients with Fanconi anemia. The only curative (relapsed or refractory)
treatment for them is HSCT. However, this will neither Neuroblastoma
Ewing sarcoma
cure the physical and renal manifestations of the disease,
Myelodysplastic syndromes
nor prevent the risk of cancer. Palliative therapy with oral
Gllomas
androgens has been used in patients of Fanconi anemia
Other solid tumors
Who cannot undergo HSCT.
- 346 I Essential Pediatrics . . ~
n -term, silastic, multi-lumen cathet
corrects genetic or acquired disease of blood and bone Venous access: A~~dfcations, infusion of stem cells, bl~
marrow. is needed for IV d . ·stration of blood components and
sampling, and a nuru
AJlogeneic Hematopolettc Bone Marrow Transplant nutrition. . .
C>oncY Requirement . 1 nd fungal infections are a rnai·
.1. • • Bacteria a or
For an allogeneic transplant, a human leukocyte antigen
(HLA) identical sibling is the ideal donor. In spite of HLA
Iti1 ectious: .
r
complic~tlo~ i~ ear appropriate antibiotics is needed.
Prompt mstiinftuho:11 °s assume increasing importance the.
1
1 and late post-transp ant perioq
~ \~t t\) 'n.~"'\t~· the 1-"'ti~nt f ro.m the my"'loto.xlclty dl~ordcr nnd mognltudc of blood loss. Administration of
.l~~ ~ 1..Th-'t'l."-'th'-~apy, Th~ P~"'iure i~ Q.nl)' lndlcatro replacement fluids/blood Is ncccssilry. Pollowing this, the
R~~-:.~l'~t~u:\'l..-k'$ wh\cl\ a~ cht..'11,0- l"\f radios~ns.Hh·e. e.g. child should be cvnlunted for the etiology of bleeding,
~~i.~"U\t~ ~-1,,ph<.1.m~ m.'urohlas«.,ma ~md Qthcr s\llld which mny be due to plntclcts (Tnblcs 13.14 and 13.15),
~Ul"-"'""$... coC\gulation defects (Tnblc 13. 16) or dysfunctional
f\">.-iph~r~l hk"'-'l st~m cdl trnnsphmt.1tions (PBSCT) fibrinolysis. Cllnicnl nsscssmcnt (including type of
hl,w~imt2Uy ttrla~'\.i lxme marrow fo.r aut()\Qgous stem bkcding nnd nntcccdcnt events) nnd results of initial
~-0 tr..t.."'l..~1.mt..lti-.~n. Engrnftmtmt takes pla~ nwre r,lpidly screening help to rnpidly identify the cause, and enable
"''~"[?. ~rirh.~r..ll $t~m cdls are used instead of bone specific mnnngement.
a":..irrcw ~ll' Tht- ..l\h-~m~~ of autluogous tr-cmsplcmt over
.ill~~k tr..u~pl::mt \$ th,,t there is no gm.ft n'~us host Tabla 13.14! causes of th'rombocytopenla ....... ..1
~:l.~ and Q.tl\.""e ~'Srnftmtmt cx~urs then graft rejection Idiopathic thrombocytopenlc purpura
~ u.·•.likely,
Infections: Disseminated lntravascular coagulation, malaria,
kala-azar, dengue hemorrhagic fever, hepatitis B and C, HIV,
~I Blood stem Cell Transplantlon (PBSCT) congenital (TORCH) Infections, Infection associated
1hefn,'-.'"\.'\.it.u-e is similar ro bo.ne marrow trnnsplnnt except hemophagocytosls syndrome
fur ditteren~ in th~ method of colk'Ction of skm cells Medications: Valproate, penlcllllns, heparin, quinine, dlgoxin
.mdslight ch~ in the engrnftm1:.-nt po~ntial. Peripheral Thrombotic microanglopathy: Thrombotic thrombocytopenlc
tlood contains 0.1":-i., :;.~m cells; this number is incrcnsed purpura; hemolytlc uremic syndrome
by J.dministration of colony-stimulating factors. For Malignancies: Leukemia, lymphoma, neuroblastoma
allogenic P&..<:;CT, administration of G-CSF for -l-5 days Autoimmune or related disorders: Systemic lupus
~-ults in higher number of circulating stem cells, which erythematosus, Evans syndrome, antlphosphollpld syndrome,
cm be collt?\.-ted by apheresis. The donor is spared the pain neonatal Immune thrombocytopenla
of marrow aspiration, For autologous PBSCT, stem cells Immunodeficiency. Wiskott-Aldrich syndrome, HIV/AIDS
are rollected similarly, but chemotherapy is given prior
Bone marrow failure: Thrombocytopenia with absent radii,
to the harYe:St ro reduce tumor contamination and yield
Fanconl anemia, Shwachman·Diamond syndrome
higher proportion of stem cells.
Marrow replacement Osteopetrosls, Gaucher disease
Cord Blood stem Cell Transplantation Others: Hypersplenlsm, Kasabach-Merritt syndrome
I
Cardiopulmonary bypass
Suggested Reading
• Seth S, Kanga U, Sood P, et al. Audit of peripheral stem cell Table 13.•16: Common coagulation di~orders
transplant for aplastic anemia in multi-transfused and infected 1
patients. Transplant Proc 2012; 44: 922-24. Inherited disorders
• Kumar R, Prem S, Mahapatra M, et al. Fludarabine, Hemophilia A and 8
cytlophosphamide and horse antithymocyre globulin conditioning von Willebrand disease
regimen for allogeneic peripheral blood stem cell transplantation
Specific factor deficiencies
performed in non-HEPA filter rooms for multiply transfused
patients with severe aplastic anemia. Bone Marrow Transplant Factor VII, X, XIII deficiency
2006; 37: 745-9. Aflbrlnogenemia
Acquired disorders
DISORDERS OF HEMOSTASIS AND THROMBOSIS
Liver disease
Approach to a Bleeding Child Vitamin K deficiency
Warfarin overdose
An important initial step is to stabilize the bleeding patient. Disseminated lntravascular coagulation
Assessment of vitals provides a clue to the severity of the
11 34e I Essential Pediatric•
Pathogenesis
I1ntr1n1lc:_Plihw1~1 I lhctrlnAln Ptttw1 '1 1
The process of hemostasis is divided into cellular and fluid Contoct 110llvollon
phases. The former involves platelets and the vasculnr VII
x11 -~ x11a
wall, while the latter involves plasma proteins. The
physiology of hemostasis is complex, involving n fine
balance between flow of blood and local responses to
vascular injury. The fluid phase is divided into three
processes: (i) multiple-step zymogen pathway thnt leads
x1 - ~x10
~
t
IX-41Xo
I Vllh1
-t ~ ----..
l Ctifllltlffi t
tl§~t19 fffu1,,
Vlf11
~~l~lurri
l
that limit clot propagation.
The physiology of hemostasis includes the generation +
of insoluble fibrin and activation of platelets to form a Pl11ttJfet ftitWr IF1Jt,'fbrX111
hemostatic plug. Pro- and anticoagulant pathways,
platelet number and their function, and vascular factors
control this process. The coagulation cascade is often
depicted as involving two pathways: Intrinsic and
extrinsic. The extrinsic pathway, the primary initiating
pathway for coagulation, is measured by prothrombin
-- i
Prothrombln (loctot II) f--•[ Thrombln (iin) \- -
[x11~f
time (PT). The intrinsic system that works as a regulatory
amplification loop is assessed by activated partial
thromboplastin time (aPTI) (Fig. 13.12). IFibrin cir.A '
Cllnlco/ Evo/uotlon Fig. 13.12: fn vivo coagulation cancado
The age at onset of bleeding, type and sites of bleeding hemophilia), females with bleeding conditiono are sc<:n
(mucosa!, skin, deep in joints or muscle), spontaneous or in autosomal dominnnt conditions (von Wil lcbrand
after intervention (dental extraction, surgery, circumcision), disease). Specific types of bleeding may as8ist Jn diagnosi$,
duration, frequency and the measures required for control e.g. poor wound healing and prolonged bleeding from
assist in defining the etiology (Table 13.17). In case of the umbilical stump suggests factor XIII dcfi cicni:y.
recent onset bleeding, history of antecedent infections, An examination is done, noting the nncmia, fod ing and
rash (Henoch-Schonlein purpura, varicella), and new ecchymoses (Fig. 13.13). The presence of petcchiae,
preceding icterus, diarrhea or dysentery needs to be vascular malformations and ras hcf-1 iB docu mented.
elicited. Important medications that may commonly cause Splenomegaly suggests infections, malignancy, C(Jllagen
bleeding are anticonvulsants, penicillin, warfarin, aspirin, vascular disorders or hypcrsplcnism rather than a primary
non-steroidal anti-inflammatory drugs and heparin. bleeding defect. Rashes may be seen due to pctcchiJc, post·
History of blood transfusions helps assess the severity of drug exposure, infections, collagen vasculilr di ,orders, 1
bleeding. Family history is important; documentation of Langerhans cell histiocytosis and Wiskott-P.J<l rich
sex of affected members and details of bleeding syndrome. The mouth nnd nose nre examined frJr local
manifestations is done. The pedigree should include the causes of bleeding. Hemangiomas and tclangiccli.I Sias lead
sex of any stillborn or dead children as well. An illness to mucocutaneous bleeding in Kasabach-Mcrritt
~--·._
.
f:, _,,
...,_ .. ,..I -
• • •
.r • - ...
syndrome and hereditary telangiectasia.
-.,.• ••• J -•
Table 13.17: Differences in bleeding patterns between platelet disorders and coagulation disorders
• • •
Suggested Reading
• Clinical and laboratory approach to the patient with bleeding. In:
Nathan and Oski's Hematology of Infancy and Childhood, 6th edn.
Nathan DG, Orkin SH, Ginsburg D, Look AT. lusher JM, eds. WB
Saunders: Philadelphia; pp 1515-1526.
Fig. 13.13: Large ecchymottc patch on the upper limb of a Idiopathic Thrombocytopenlc Purpura (ITP)
young girl with von Wlllebrand disease ITP continues to carry its acronym, although the condition
is no longer idiopathic, and is considered to have an
Laboratory lnvestlgof/ons immune basis. This is the commonest bleeding disorder
A hemogram is done for platelet count, morphology of presenting in children between 1 and 7 years of age. It is
platelets and red cells, and screen for microangiopathic important to correctly diagnose this entity and differentiate
hemolysis. The peripheral smear is made from a fresh it from other ominous conditions. Thrombocytopenia
finger stick, avoiding artefactual errors due to EDTA lasting less than 6 months is termed acute, and greater
anticoagulation. Initial screening tests are PT and al"IT than 6 months is termed chronic. The majority of children
(Pig. 13.14). Specific factor assays are done to identify and (60-75%) are likely to have acute ITP that resolves within
grade factor deficiencies. The a PTT is used for monitoring 2-4 months of diagnosis, regardless of therapy.
heparin thcrapyi PT and ratio of PT to an international
normalized standard (INR) are used to assess therapeutic Pathogenesis
warfarin affect. Normal platelet counts vary between 150 and 400 x 103I mm3
Bleeding time is rarely used due to the problems of in children above one week of age. ITP is believed to have
reproducibility and reliability. This test is abnormal if the an immune pathogenesis, against the platelet glycoprotein
platelet count is below 100,000I µL (Table 13.14). In systemic Ilb /IIIa complex. Platelets with surface antibodies are
vasculitic disorders (Henoch-Schonlein purpura) and trapped in the spleen, and removed by macrophages. The
..
PT and aPTT Normal PT
•
Hemophilia A and B
Normal aPTT
Anticoagulant therapy
Infection Oral anticoagulants
Hyper1plenl1m Liver dysfunction von Wlltebrand Factor VII deficiency
Immune thrombocytopenla Vitamin K deficiency disease
Thrombotic mlcroanglopathy Disseminated lntravascular
coagulatlon
M1llgn1ncy
Fanconl anemia
Thrombocytopenla with
abHnt radii
Platelet dysfunction
Fig. 13.14: Work-up In a child with bleeding
1111, ~ l ~~~~~~~~~~~-E_s_s_en_t_la_l_Pe_d_le_t_rlc_s~-------------~~~~-~
karyocytes and help exclude marr
llbl.1s..1~ ~~f-~~ ot bleeding production ofbmegamarrow failure.
infiltration or one
o...,.
~~~~ purpura
\~t$ lh ~~~c l\J~ ~C)rthematosus Management . . . .
Si.~acll~ ~~ f . ns need to be avoided. M1rum1zing th
Platelet trans usio d decreasing the long-term .de
~' · k f h morrhage an 51 e
ris o e t are the goals of therapy. In a child
~~ s~ro{d ~CWltng d~ase ff ts of trea tmen . l
e .ec tt red petechiae or brmses, p atelet count
~ hern<:mh~ telangtectasia with a few sea e · nl 1 b
000 /µ L and no bleeding, o y c ose o servatton
above 20
. . ' d F0 r children wit · h bl ee d'mg, t reatment
f'lth.O~"\e~i$ of these antil'-odies is not known. The is require · b l' (IVIG)
antib..ld.ies ma\' be directed tQward.$ \iral antigens, which . 1 d i'ntravenous immunoglo u m 1 g/kg/
me u es -2 days· or anti-D · immunog
· 1ob um
i· 50-75 mg/
then cro'5.S-react with platelet antigens. Recent data day for 1 ' S 'd d . .
d~be:s a THl dominant pro.inflammatory cytokine k only in Rh positive children: term s ar.e a mirUstered
s!'are~ While increa.~ m~akarvoC\ie aTter hematological mahgnancy is excluded.
'-' . . number in the bone Dexamethasone 20 mg/m2 (total dos~) for 4 days every
marrow is the hallmark of immune-mediated platelet
destructio~ a relath·e decrease in megakaryocyte three weeks for 4-6 courses, or predrusone 1-2 mg/kg/
productio..."'l. due to specific anti-platelet autoantibodies is day for 2-3 weeks or 4 mg/kg/ day for 7 days and then
al."'O implicated in the pathogenesis. tapered have been used. If serious hemorrhage occ~rs,
platelet transfusions may be u~ed ~der cover of steroids.
O !ni'cd E\'cllcibn Therapeutic options for chrome ITP mc~ude alte~ate.day
rn.e..i..-e is often an antecedent history of febrile illness, but low dose steroids, splenectomy and various combinations
the child on presentation is afebrile. There is a seasonal of danazol, vincristine, cyclosporine, azathioprine or
clustering of cases, more frequent during change of rituximab.
sea.~ Children present ''ith a sudden appearance of
bru.L~ and mucosa! bleeding: Epistaxis, oral oozing and
Suggested Reading
prolCIDooed bleeds "ith superficial trauma. It is important • Nugent D. ASH education book 2006. www.asheducation
to estimate the duration of symptoms, and confirm if this book.org/cgi/reprint/2006/1/97 /pdf.
is the initial episode or if there ha,·e been prior eYents, as • Shanna SK, Gupta N, Seth T, Srinivas M, Mishra P, Mahapatra M.
Successful management of refractory chronic immune
in the chronic ITP. The patient is examined for features of thrombocytopenia with intracranial hemorrhage by emergency
marrow failure (Fanconi anemia: Hypoplastic or absent splenectomy. Indian J Pediatr 2012; 79: 397-399.
thumb, short stature and hyperpigmentation; thrombo-
cytopenia with absent radii) and large hemangiomas. Neonatal Allolmmune Thrombocytopenla
Bleeding is mild unless the platelet counts are below Thrombocytopenia in the neonate has varied cause:;; a sick
20,000/µL. With counts from 20,000-50,000/~tL, petechiae newborn may have sepsis, meconium aspiration, and
and ecchymoses are observed follm-.ing mild trauma. The TORCH infection. In a well looking infant, the causes may
presence of splenomegaly or lymphadenopathy should be medications taken by the mother or immunologic
raise suspicion of infection, malignancy or collagen causes like maternal lupus erythematosus or neonatal
vascular disorder, rather than ITP. Hypersplenism and alloimmune thrombocytopenia. In neonatal alloi.rrunune
hepatitis C may also cause thrombocytopenia. thrombocytopenia, the fetal platelets are destroyed by
passage of maternal antibodies against paternally
I
Laboratory Evaluation
inherited antigens present on fetal platelets. Many platelet
Complete blood count shows that only the platelet count antigens, like HPA-la and HPA-Sb, have been identified.
is diminished; other hematological parameters are normal. No prior pregnancy is required to sensitize the mother;
A peripheral smear will help screen for abnormal cells hence 50% of cases may occur with the first pregnancy. A
such as blasts, malarial parasites, estimate the platelet high index of suspicion is required, since the entity can
count, and exclude spurious thrombocytopenia. It will also result in intracranial hemorrhage. As there are a fe'."'
help to assess platelet size: Larger platelets are young and specific t~sts for its ruagnosis, it is primarily a diagn~SJ.5
art indicator of platelet production. Liver and renal of exclusion. Postnatal management requires transfusion
function tests and lactic dehydrogenase is done to rule of washed, maternal platelets (irradiated, if facilities .are
out the possibility of hepatitis, occult malignancy, available) and monitoring until platelet counts normaliZ~·
hemolysis and hemolytic uremic syndrome. If the child is The risk for neonatal alloimmune thrombocytopenia
febrile and ill, then appropriate evaluation is required; this increases in subsequent pregnancies. The fetus might n~
includes chest X-ray, blood culture, tests for malaria or serial ultrasound examinations to screen for intrac.r aru;
dengue serology. Screening tests for disseminated hemorrhage. The mother may receive therapy with )
intravascular coagulopathy should be done, if sepsis is immunoglobulin (IVIG 1 g/kg repeated every 4-monthlY
suspected. A bone marrow will show increased and oral dexamethasone.
I ~
Suggested Reading
• Controversies concerning vitamin K and newborn. American
Academy of Pediatrics Committee on Fetus and Newborn.
Pediatrics 2003; 112: 191-2.
I
Cryoprecipitate Fibrinogen 150 mg/bag, Fibrinogen deficiency 1 bag per 5 kg will raise
factor VIII 80-120 units/ or consumption; factor fibrinogen levels by
bag, factor XIII and vWD VIII deficiency (hemo- 70 mg/dl
(does not contain factor philia A), vWD disease;
IX) factor XII I deficiency
. Random donor Platelets; ~5.5 x 1010 Thrombocytopenia One unit raises platelet Infuse rapidly; do NOT
' platelets (ADP) platelets per bag counts by 5000-10,000/ refrigerate prior to transfusion
mm3 ; 1 unit every
1o kg raises counts
by 30,000-50,000/mm 3
Sfngle donor Platelets; contains at least Thrombocytopenia One collection is equi- Precautions as above
, Platelets (SOP) 3 x 1011 platelets valent to approxi-
mately 6 units of
random platelets
· Fresh blood All components of blood To replace acute and Only to be used in Not a good source for platelets
' massive blood loss severe trauma or coagulation factors
354 I Essential Pediatrics
. th b ..
due to deep vein rom osis me ude p~
l~ .
Novel t11erapies: Supplementation with activated protein Sy~~w
. of the limb· erythema and tenderness on f
C has shown promise in critically ill patients. High-dose and swe11mg '. b oot
'fl · n (Homan sign). may . e seen. b Pulmona ry
therapy with antithrombin III has shown benefit in some d orsi ex10
neonatal studies. embolism may present with anxiety, reathlessness,
'ti hest pain, fever and cough. Symptoms of central
p1eun cc thrombosis . 1u d e h ead ach e, vomitin
. me
Suggested Reading nervous syStem . . g,
• BCSH Secretary, British Society for Hematology. Guidelines for
lethargy, seizures, focal weakness or hem1pleg1a. Strokes
diagnosis and management of disseminated intravascular may occur in utero; the ne':~o~ may then pre~ent With
coagulation. Br J Haematol 2009; 145: 24-33. seizures and lethargy. Precipitating factor.s hke infection,
dehydration and trauma are co?'mon. Pa hen ts.wit~ renal
THROMBOTIC DISORDERS vein thrombosis show flank pain and hematuna. Signs of
arterial thrombosis include diminished or absent
The incidence of thrombosis is lower in children than
adults; thrombosis related morbidity is, however, peripheral pulses and cool extremities.
significant. Children till 6-month-old have lower levels of
Laboratory Evaluation
the vitamin K dependent coagulation factors II, IX, and X,
compared to adults. Levels of thrombin inhibitors, such Since clotting factors are consumed in an acute thrombosis,
as antithrombin and heparin cofactor II, plasminogen, their low level may be the result of the pre-existing
protein C and Sare low at birth. Protein S levels approach thrombosis. The child should be evaluated to rule out DIC
adult values by the age of 3-6 months, but protein C levels with complete blood count, peripheral smear, D-dimer,
are low even into childhood. Thrombin generation is prothrombin time (PT), activated partial thromboplastin
decreased (low prothrombin levels) and delayed in time (aPTI) and fibrinogen level.
newborns compared to adults. The incidence of Imaging studies include: (i) Color Doppler imaging.
thrombosis is highest in infants and in adolescence. Signals are absent in thrombosed vessels and the lumen
cannot be compressed with direct pressure. However,
Clinical Evaluation this may not be sufficient!y sensitive to detect thrombosis
Conditions associated with arterial thrombosis include in vessels such as subclavian veins, superior vena cava
congenital heart disease, recent cardiac catheterization, or brachiocephalic veins; (ii) Echocardiography. This is
fever, recent surgery, trauma, central venous catheter use, useful for vena cava and proximal subclavian vein
and underlying nephrotic syndrome, collagen vascular thrombosis; (iii) Computerized tomography. Useful for
disease and dehydration (Table 13.22). The age at which detecting venous sinus thrombosis; however, both MRI
thrombosis occurred and type of thrombosis (deep vein, and MRA are better at detecting early arterial ischemic
arterial or stroke) should be documented. strokes; (iv) Chest radiography. Reveal find ings of
. - . pulmonary embolism which include small pleural
Table 13.22: Factors which increase risk of effusions with wedge-shaped pleural-based opacity of
thrombosis in children pulmonary infarction; (v) Ventilation-perfusion (V /Q)
Acquired conditions scan. Sensitive procedure for detecting pulmonary
Infections: Viral, bacterial sepsis embolism.
Disseminated intravascular coagulation
Management
Dehydration
Central venous catheter Urgent stabilization is required. If respiratory discress or
Surgery, trauma neurological problems exist, management in an intensive
Cyanotic congenital heart disease care unit is required. If possible, screening t~sts for
Antiphospholipid antibody syndrome hypercoagulable state should be sent prior to initiating
Acute lymphoblastic leukemia; therapy (L-asparaginase and anticoagulation therapy. Children with lower extremity
steroids) deep vein thrombosis can be fitted for compression
Nephrotic syndrome stockings. Initial therapy requires heparin (unfracti:mated,
Inherited prothrombotlc disorders
low molecular weight) followed by oral warfarin therapy.
While underdosing hampers resolution of the thrornbUS1
Resistance to activated protein C close monitoring is required to prevent overdose and risk
Factor V Leiden of bleeding. The international normalized ratio (fNR),
Protein C deficiency which is PT of patient compared to an international
Protein S deficiency standard, is kept in the therapeutic range -2-3. The
Antithrombin deficiency duration of therapy depends on the risk of recurrence;
Prothrombin gene G20210A mutation this can be assessed by testing for thrombophilia sta~'
Elevated lipoprotein (a) level best done 3 months after the event and after stoppiilg
Hyperhomocystelnemia anticoagulants.
Hematologlcal Disorders 355
11 entero.pathy and following treatment with anti-thymocyte q~antitative ~efects in T, B or both lymphocyte subsets
globulin and corticosteroids. with maturation or functional defects, which may lead to
life-threatening infections.
Qualitative Defects
Suggested Reading
Cl1ediak-Higasl1i syndrome is identified by characteristic
giant lysosomes in granulocytes and oculocutaneous • The phagocytic system and disorders of granulopoiesis and
albinism. The condition is due to defect in CHS1 gene that granulocyte function. In: Nathan and Oski's Hematology of Infane)'
and Childhood, 7th edn. Eds. Orkin SH Nathan DG Ginsburg D,
encodes for lysosomal trafficking, resulting in ineffective Look AT, Fisher DE, Lux SE. WB Saund~rs Philadel~hia, 2009; PP
granulopoiesis, delayed degranulation and defects in 1109-1220. I
·· ·-·- -------~ . . - _.............
Otorhinolaryngology
Prem Sagar • Alok Thakar • Sandeep San:iant
DISEASES OF THE EAR and irritability. Older children may report impaired
hearing. History of recent upper respiratory tract infection
Acute Otltls Media is common. Otoscopy reveals a red and bulging tympanic
Otitis media is a common early childhood morbidity that membrane or perforation of the tympanic membrane with
refers to viral or bacterial infection of the 'middle ear cleft'. otorrhea (opaque, yellow-green or reddish-brown fluid).
The middle ear cleft is a term that includes the pneumatic Cleaning of the fluid reveals an intact drum, as the rupture
spaces of the middle ear cavity medial to the tympanic is small and closes promptly after spontaneous
membrane, the attic superiorly, the mastoid antrum perforation. The diagnosis of otitis media is considered in
posterior to the attic, and pneumatized air cells in temporal the presence of the following criteria: Rapid onset of
bone that surround the mastoid antrum and extend to the symptoms, signs of middle ear effusion and signs and
petrous apex. Anatomic features that predispose a young
symptoms of middle ear inflammation.
child to ear infections include a shorter, more horizontal
and compliant eustachian tube, and bacterial carriage in Treatment: Antimicrobial therapy is recommended in all
the adenoids. Risk factors include exposure to cigarette patients except a few who may qualify for a trial of
smoke, overcrowding, bottle feeding, use of pacifier, day observation (Table 14.1). Amoxicillin is the first choice of
care center attendance, cleft palate, Down syndrome, therapy. Higher doses (80-90 mg/kg/ day) are considered
allergy, immune dysfunction and gastroesophageal reflux. where streptococcal resistance is endemic. Coamoxiclav,
lllcidence: The peak incidence of acute otitis media in cefaclor, cefuroxime and newer generation cephalosporins
childhood is in infancy and decreases with advancing age. are useful second-line drugs. Macrolides are considered
Acute otitis media is uncommon beyond the age of 7 years. in patients allergic to penicillin and/ or cephalosporins.
Etiology: The most common causative organisms are Antibiotic therapy is continued for at least 7 days.
Streptococcus pneumoniae, Haemophilus influenzae and Otoscopy should be repeated after 3- 4 days and at
Moraxella catarrhalis in -75% cases; less common pathogens 3 weeks. Adjuvant treatment with oral and topical
include S. pyogenes, S. aureus and Pseudomonas aeruginosa; decongestant agents is not necessary. Antihistaminic
Viruses may be the sole pathogen in 15% of cases. agents, which contribute little to resolution of otitis media
Diagnosis: The condition is characterized by rapid onset and may precipitate sinus infections by drying mucosal
of symptoms such as otalgia or ear tugging, fever, crying secretions, are not recommended.
Age, months
- -· ~-·-- Table 14.1: Recommendations for initial management for uncomplicated acute otitis media-
se~ere symptoms*, otorrhea or uncertain access to
follow-up
No severe symptoms• or otorrhea;
follow-up assured
I
Unilateral Bilateral Unilateral Bilateral
6-23 Antibiotic therapy Antibiotic therapy Treat or observe** Antibiotic therapy
~4 Antibiotic therapy Antibiotic therapy Treat or observe** Treat or observe**
?linlca1 practice guideline: Diagnosis and management of acute otitls media. Pediatrics 2013; 131 :e964-99
.~~elude toxic-appearance; otalgla persisting for >48 hours; temp.erature >39°C (102.2°F) in last 48 hours
off Observation Is offered, follow up must be ensured and antibiotics are begun If the child worsens or falls to improve within 48 to 72 hours of onset
8Ymptoms
357
- 3so I Essential Pediatrics
· .
Test
.. . · . .
Principle
Child Educ Pract Ed 2015; 100:193-7.
Age of child
Automated otoacoustic emissions Evaluates cochlear function; also affected by ear Any age; neonatal screening
canal obstruction or middle ear effusion
Automated auditory bralnstem response Measures integrity of cochlea, auditory nerve and Any age; neonatal screening
brainstem
Visual reinforced audiometry Sound booth based conditioned hearing · 8 months to 2.5 years
Play audiometry Play/game reinforced hearing evaluation >2.5 years
Audiometry Ear and frequency specific hearing assessment >4 years
1363 -
Fig. 14.Sa: X-ray (modified Stenver view) of the mastoid shoo•fn:J Ag. 14 .5b: Cccnear rnp lantee in a rehabilitation session. Note
cochlear implant with multichannel stimulating~ c::crig me &-=-rncl CD"'T'lp orent L1cluding a microphone behind the
the cochlear turn (arrow) . Note the receiver stimulator p.i"J.')Q ard a iianSl1Lit'er superio.iy over 1he mastoid 1hat tronsmlts
component placed pasterosuperiorty and the bal!Jg '.ound cm.p':.i'led s:xi"Xl to the internal recelver stimulator complex
electrode located superiorty trcnscutcnoous..ly
smear, skin tests for common allergens and increased
DISEASES OF NOSE AND SINUSES serum total or allergen-specific lgE are not essential.
Further, skin tests may . be negatiye
~
in cl1ildren durin~
" the
Rhinitis first 1-2 years of illness while the sensitization is confined
Inflammation of mucosa lining the nose may occur alone to nose and sinuses. Differential diagnosis includes food
(rhinitis) or with paranasal sinuses (rhinosinusitis). allergy (egg protein, cow milk, sea food). Management
comprises of allergen aYoidance. Topical corticosteroid
Viral Rhinitis sprays proYide symptomatic relief. Topical decongestants
Viral rhinitis (common cold) is the most frequent cause of are discouraged due to the risk of rebound congestion and
nasal obstruction and rhinorrhea in children, occurring rhinitis medicamentosa.
up to 6-8 times a year, usually due to infection with Bacteria l Rhinosinusitis
rhinovirus, influenza or adenovirus. Symptoms include
malaise, low to moderate grade fever, nasal congestion Four pairs of paranasal sinuses surround the nose and
and rhinorrhea, with or without sore throat. Antipyretics, help humidify inspired air. The maxillary and ethmoid
saline nasal drops, oral decongestants and antihistamines sinuses are present at birth and get easily infected in
provide symptomatic relief. Annual influenza vaccination childhood. Sphenoid and frontal sinuses develop at
reduces the incidence of severe cases. Less than 5% approximately 9-10 months and 7-8 years of age,
affected children develop superimposed bacterial respecti' ely, and rarely get infected alone.
rhinosinusitis and suppurative otitis media. Acute bactcrit?l r11i11osi1111sitis: Rhinosinusitis is termed
acute, if symptoms are for less than 12 weeks. lt usually
Allergic Rhinffis follows viral rhinitis, but may develop dt 110Po and re-
The condition is due to an IgE-mediated reaction to specific currently in the presence of predisposing factors such ns
allergens, commonly inhaled house dust mite, pollen and allergic rhinitis, adenoid int1ammation and hypertrophy,
spores. Coexisting atopic dermatitis an~ as.thma are cystic fibrosis, immunodeficiency, cili~uy dyskincsia,
common. Presentation is with sneezing, itching, nasal daycare attendance, exposure to tobacco smoke and
obstruction and clear rhinorrhea that are seasonal (hay gastroesophageal reflux. Viral infections cause mucosal
fever) or perennial with intermittent exacerbatio~s. edema and ciliary hypoacth ity causing obstruction of
Examination shows pale nasal mucosa, hypertrophied sinus ostia (openings of sinuses into the nasal cavity) nnd
nasal turbinates and thin mucoid rhinorrhea with or stasis of secretions. Obstrncted sinuses are likely to get
W~thout conjunctiva! itching and redness. ~iagnosis is infected bv bacteria from the nasophnrynx, usually S.
clinical; supportive tests such as eosinophilia on nasal pneumoniae, H. i11flue11zne and M. catarrlmlis.
- ~64 I .. . , Eaaentlol Padlatrlc:e
Epistaxls
Fig. 14.7: Lateral radiograph of the neck showing adenoid
hypertrophy occluding the nasopharyngeal airway in a 6-year-
Bleeding from the nose is frequent in children and usually
old boy (Courtesy: Textbook of ENT, Hazarika) follows injury to the anterior portion of the nasal septum
in Little's area, the location of Kiesselbach nrterial plex us.
reflux with proton pump inhibitors. Adenoidectomy is Bleeding follows local trauma, especially by nose picking
recommended in the presence of adenoid hypertrophy during hot summer days, when reduced ambient
that is associated with persistent or recurrent otitis media humi~ity ~auses crusting in the anterior nasal cavity.
with effusion, failure of medical management for obstruc- Exammation reveals prominent vessels that bleed
tive sleep apnea, chronic adenoiditis, craniofacial growth promptly when touched with a cotton-tipped probe or a
abnormalities due to prolonged airway obstruction and dried clot ?ve~ Litt~e's area. Avoidance of nose picking,
chronic rhinosinusitis. Adenoidectomy is also done for use of lu~ncatmg ointment and pinching the nose to stop
patients with concomitant cleft palate or submucous cleft the bleedm.g are tau?ht to the child and parents. Refractory
palate so as to avoid uncovering symptoms of velo- cases reqmre chemical- (topical silver nitrate) or electro·
pharyngeal insufficiency, such as nasal regurgitation of
fluids and hypernasal speech that are masked due to
compensation by hypertrophied adenoids.
Choonat Atresta
This term refers to congenital failure of the nasal cavities
to open into the nasopharynx. Unilateral or bilateral
choanal atresia or stenosis is hypothesized to be caused
by complete or partial persistence of buccopharyngeal Fig. 14.8: Axial computed tomography of paranasal sinuses
rnernbrane (separating oral cavity from pharynx). or showing right (R)-slded bony and membranous choanal otresla
llasobuccal membrane (separating nose from oral cavity) and left (L)-sided complete bony atresla
- ~ 1 Essentlal Pediatrics
.
.
d cleft palate occur d ue to incomplete fusio
~
cauh:.'rii:ati0n. Coagulopathy should be ruled out in
childrt'n with family history, bleeding from other sites or Cleft lip a~ in maxillary and nasal processes. Cleft Iin
refr,1ct\.)ry \)f Sl'\'ere epist<lxis. Uncommon causes of of the deunilv~ otp ra~ or bilateral, and incomplete (when""'~
maybe ae . t d 'th cl ~·11}
n..-current ~ph~taxis include juvenile nasopharyngeal . 1s
the hp . b 1'fid) or complete (assoaa e W1 b .eft in the
iln$io.fibroma and hereditnrr hemorrhagic tel<mgiectasia 'd e) Likewise, cleft pa1ate may e unilateral a
a1veo lar n g · f · l t r
(~k~Weber·R~ndu syndrome), the latter presenting . d incomplete (c1e t m pa a e posterior 1
bilatera1, an cl ft · l · . o
\\ith ~\'ere rt.'Current epistaxis, gastrointestinal bleeding incisive foramen) or complete (. e mvo vmg entire length
J.nd pulmonary hemorrhage. % cases of cleft lip or palate are assoctato...1
of pa lat e.) 40 . d · · ~~
with other congenital anomalies; s~ rorruc assoaations
S\Jggested Reading · 1 d Goldenhar and Treacher Collins syndromes. Cleft
• Bes.wick D!\t. :l.h:ss ner AH. Hwang PH. Pediatric chronic pa a ee leads to feeding difficulty,
mclut h . abnormal. . nasal
rhinos inusiti:: management in rhinologists and pediatric breathing, abnormal speech, eanng i~pamnent and
otol..uyn,.i:olo~ists.. Ann OtuJ Rhinol Laryngol 2017; 126:6~9. impaired dentofacial growth. Sta~ed surgical reconstruc.
• Klostum.m. T. The m;inagement of Yascular malformations of the tion of the lip and palatal defects 1s performed.
J.irway: :-.fotur.il history. im·estigations, medical. surgical and
r:idiolo~ical m.magement. Otolaryngol Clin North Am 2018;
:;-1:.. 13-~"l. Micrognatltia refers to a dispr?portiona~ely small
mandible. Congenital micrognathia may _be isolated or
DISEASES OF ORAL CAVllY AND PHARYNX associated with Pierre Robin sequence (with cleft palate
and glossoptosis). Unilateral mandib~ar.hypoplasia m~y
Inflammatory Disorders present with other features. o~ hem1~ac1al n:acrosonua.
Rt!currrrrt npl1tl10us stomatitis presents as variably-sized Micrognathia may cause difficulty m feedmg, dental
painful white ulcers with surrounding erythema, located overcrowding and in severe cases where the tongue is
on the oral mucosa and/ or tongue. The precise etiology displaced posteriorly, breathing difficulty. Milder cases
is unknown. Minor (<1 cm) ulcers resolve spontaneously resolve spontaneously. Neonates with breathing difficulty
over se,·eral days. ?\ lajor ulcers (> 1 cm) are less common, require prone nursing and/ or oropharyngeal airway.
may affect the soft palate or tonsils, and heal slowly (4-6 Severely symptomatic patients require surgical
weeks) sometimes with scarring. Though most cases are procedures like tongue advancement, mandibular
idiopathic, recurrent ulcers are seen in Behcet disease and distraction osteogenesis or tracheotomy.
cyclic neutropenia. Symptomatic management includes
Macroglossia refers to disproportionately large tongue
local application of protective and analgesic pastes or
anesthetic gels, failing which topical or, rarely, systemic compared to other structures of the oral cavity. Cases may
steroids may be tried. be idiopathic or syndromic, associated with Down or
Beckwith-Wiedemann syndromes, neurofibromatosis or
Herpdic stoma ti tis caused by herpes simplex virus type congenital hypothyroidism. Macroglossia may be
1 is highly contagious. Erythematous gingiva and mucosal acquired, due to infections, trauma, tumor or vascular
hemorrhage are associated with clusters of painful malformation. The condition may lead to drooling, speech
vesicles, e\·olving to gray pseudomembranous mucosal impairment, feeding difficulty, abnormal grov1th of
ulcers. Symptomatic treatment includes analgesics and alveolus and dentition, or airway obstruction. Speech
oral or intravenous hydration. While oral acyclovir hastens rehabilitation and/ or surgical reduction may be needed.
recovery, lesions usually heal spontaneously in 10-14 days.
Oral cmrdidiasis (thmslr) caused by Candida appears as Stuttering, Stammering
small white curd-like lesions on tongue and oral mucosa.
Stuttering is dysfluency of speech characteri zed by
While common in infants <6 months of age, the condition
abnormal repetition of syllables and prolonged
is often seen in patients receiving prolonged antibiotics
Congenital Disorders
interruptions. The most common pattern is development~!
stuttering, appearing usually at 3-4 years, when there is
inappropriate stuttering for the level of language
development. Acquired stuttering is uncommon and may
follow emotional trauma or neurological illness. Stutter~g
is usually not associated with structural orofacial
A1tkyloglossia (tong11e tie) refers to limitation of ~terior anomalies like tongue tie or adenotonsillar hypertrophY·
tongue mobility due to congenitally short lmgual Surgical intervention for these abnormalities is not useful.
frenulum. Mild forms are common, do not affect speech Mild forms of dysfluency improve spontaneously;
and improve as the patients grow. A very short and ti?ht persistent stammering requires speech and langu~ge
frenulum might restrict tongue protrusion beyond ~e lips, therapy starting in preschool years. Delayed interventlO~
may be associated with clefting of the tongue tip, and is associated with persistent stammering into adulthOO
interfere with feeding and speech. and significant psychosocial morbidity.
r Otorhlnolaryngology j 367 -
r-::-Throal
Viral pharyngiti~ is common and caused by rhinovirus,
iJlfluenza or parainfluenza virus, adenovirus or coxsackie
vi.rUS· Patients present with fever, sore throat, dysphagia,
rhinorrhea, nasal obstruction, cough and bodyache.
Exaxnination shows non-exudative erythema of pharynx
and tonsils and tender cervical lymphadenopathy.
supportive treatment with analgesics, saline gargles and
saline nasal drops is sufficient. Antibiotics are required in
cases of secondary bacterial infection.
Infectious mononucleosis, caused by Epstein-Barr virus,
affects teenagers and is transmitted via body fluids,
commonly saliva. Patients present with fatigue, high fever,
malaise, sore throat, dysphagia and odynophagia.
Examination shows enlarged tonsils, edema of soft palate,
palatal petechiae, significant cervical lymphadenopathy,
hepatosplenomegaly, and a fine rash over arms or trunk.
Differential leukocyte count indicates that over 50% are Fig. 14.9: Acute staphylococcal pseudomembranous tonsillitis
lymphocytes and more than 10% lymphocytes have an with unilateral hypertrophy of the right tonsil. This condition has
atypical appearance. Monospot or Paul-Bunnell tests are to be differentiated from other causes of white patch on the
useful for screening; presence of anti-VCA IgM antibody tonsil (Courtesy: Textbook of ENT. Hazarika)
confirms the diagnosis. Management is supportive,
comprising of hydration, bed rest, analgesics and strongly suspected, therapy against Streptococcus should
antipyretics. Patients with respiratory difficulty or extreme begin without awaiting microbiological confirmation.
dysphagia due to severely enlarged tonsils may require Initial therapy is with penicillin or a first generation
corticosteroids. Ampicillin may cause generalized itchy cephalosporin for 10 days. Coamoxiclav, clindamycin or
maculopapular rash and should be avoided. Severe airway erythromycin and metronidazole are considered in
obstruction may necessitate tonsillectomy or tracheotomy. refractory cases. Complications include peritonsillar,
Diphtheria: Though its incidence has declined parapharyngeal or retropharyngeal abscesses; non-
significantly following immunization, early diagnosis of suppurative complications are scarlet fever, acute
this potentially lethal condition is critical. The patient rheumatic fever and poststreptococcal glomerulonephritis.
appears ill and toxic. Examination shows exudative
tonsillopharyngitis with a thick gray membrane over the Tonsillectomy
tonsils extending to the palate, pharynx and occasionally Indications for tonsilloadenoid resection include
larynx that bleeds when removal is attempted. Cervical adenotonsillar hypertrophy causing obstructive sleep
lymphadenopathy is common. Gram staining and cu~~e apnea, speech defects, craniofacial growth abnormality,
confirms infection with the causative Gram-positive dysphagia, failure to thrive or cor pulmonale. Other
bacillus Corynebacterium diphtheriae. Clinic~! su~picion ~s indications for tonsillectomy are recurrent acute tonsillitis,
enough to warrant immediate treatment with diphtheria recurrent tonsillitis associated with valvar heart disease
antitoxin without awaiting microbiological confirmati~n. or recurrent febrile seizures, recurrent peritonsillar
Therapy is with high dose penicillin or erythromycm. abscess, infectious mononucleosis with severely
Airway obstruction is managed with tracheotomy. obstructing tonsils refractory to medical management, and
Acute bacterial phanpigotonsillitis is usually caused by suspected tonsillar neoplasia.
group A 13-hemolytic streptococci. Les~ common Obstructive Sleep Apnea
pathogens include non-group A streptoc.occ1, S. aureu~,
H. influenzae, M. catarrhalis, diphtheria, gonococ.ci, Obstructive sleep apnea is characterized by partial or
Chlamydia and Mycoplasma spp. Pharyngitis prese.nts with complete upper airway obstruction during sleep. The chief
fever, throat pain, odynophagia and ?~cas10nally, etiology is adenotonsillar hypertrophy. Disease associa-
headache, abdominal pain, nausea and vomiting. ~nlarged tions include obesity, allergic rhinitis, laryngomalacia,
erythematous bilateral tonsils with yellow follicles ~re mucopolysaccharidoses, Down syndrome, craniofacial
t}rpical (Fig. 14.9). Severe cases show purulent ex~dation syndromes, cerebral palsy, hypothyroidism and nasal
With or without membrane formation on tonsils, and masses. Sequelae of obstructive sleep apnea are
c:rvical lymphadenopathy. A rapid strep test ~e.l~s hypoxemia, hypercapnia and acidosis that contribute to
d15tinguish viral from streptococcal pharyngotonsillitis; behavioral and neurocognitive impairment with poor
negative results should be confirmed by throat culture. If learning, attention deficit and hyperactivity, cardio-
11111 968 I ~~~~~~~~~~~~E~s~ae~n~tl~al~P~e~d~la~tr~lc!s------------~~~~---~
VftRculnr segue Jae (systemic and pulmonary hypertension Infections
and cor pulmonale), and metabolic complications such aclreobrotrcliitis (croup) is a viri\I up
Acute lanprgo tr ff ch'ld Pl't
ilR rr.duced Insulin sensitivity, failure to thrive and . t t infection that a ects 1 ren, 6 month
respiratory rac · h b' s
dyallpidemla. Patients present wH tphasic Strid
to 3 years o f age · · f f or,
Pnrents complain of the child snoring, choking, . h and low-grade ever a ter 11n ei:iisod" f
b ark mg coug r ~· o
holding breath, sleeping restlessly, frequent arousals, ld Symptoms may evolve over several d 1~,
common co · . . . ;s.
excessive daytime sleepiness, morning headaches and/ Ch tes X - ra y reveals characteristic
, narrowing
, . . of th•~
or enuresis, Other daytime symptoms include tic region known as the steep 1e sign (Fig. li.lO)
SUb gl 0 t I • d l . 1 ') .
hype rnctivity and inattention, moodiness and poor Most cases of croup are mild an re~o ve m -- days With
Rcholastic performance. Examination reveals obesity, rvative management, includmg reussurnnce, cool
conse b l' d . I .
sleepiness, adenotonsillar hypertrophy, high arch palate, 'st and oral hydration. Ne u ize epmcp 1rme (l:lOQo
m1 . f5 '
lnrgc tongue, long face and/ or retrognathia. The in doses of 0.1--0.5 mL/kg, to a m ax1mun: o ~ ml) provides
diagnosis is ascertained by polysomnography (sleep symptomatic relief. A single dose ot dcxn~1,e t~:i\sone
s tudy) lha t analyzes electroencephalography, electro- (0.3--0.6 mg/kg, intramuscular) reduces seventy, 1! gi\'l'n
ocu Jogra phy, electromyography, oral and/ or nasal within the first 24 hours. Inhaled budesonicte ( l mg twice
nirflow, electrocardiography, pulse oximetry, respiratory a day for two day s) also shows s a tisfoc.tory results.
efforts, end tidal or transcutaneous C0 2, sound Antibiotics against Stapliylococc11s and H. 11if111t'llZnt' are
recordings (for s noring) a nd continuous video indicated, if the child fails to improve and/ or purull.'nt
monitoring during night's sleep in the sleep laboratory. secretions are present.
The Apnca-Hypopnea Index, that estimates the number
of apnca and hypopnea events per hour of sleep, Acute epiglottitis (supraglottitis), due to infection with
indicates the severity of sleep apnea; value> 10 suggests H. injluenzne type B, is less common but a more SC\ 'l're
severe obstructive a pnea. Sleep study a lso helps illness than croup. The incidence has declined following
differentiate between this condition and central apnea, improving immunization against Hn1m1opl1il11s. Piltients,
periodic breathing and central hypoventilation usually ~ years of age, present with acute sore throat,
syndromes. high fever, muffled voice, inspiratory s tridor, marked
d ysphagia and drooling. Unlike croup, cough is m un\ly
Adenotonsillectomy is the treatment of choice for severe
absent. The patient looks toxic and prefers to sit in ;,
obstructive sleep apnea. Tracheotomy may be considered
leaning fonvard, 'tripod' position that helps them brcilthe
in the most severe cases. Children younger than 3 years
better. Latera l neck X-ray reveals a c h a r .l c t~ r i stic
and those with severe apnea, obesity, cardiac complica-
thickening of the epiglottis (' thumb p ri n t' sign).
tions or neuromuscular disorde r s r equire careful
monitoring postoperatively. Maneuvering of the oropharynx or laryn x is not ,1dviscd
as it might precipitate fatal laryngospasm. Rapid airway
management is crucial and includes intuba tion by ~killl'd
DISEASES OF THE LARYNX AND TRACHEA personnel or rigid bronchoscopy fo ll O\n ' d by
tr~cheotorny. ~atypical presentations, a skilled physician
Stridor
might try flexible endoscopy, which sh ow s si ~' i iicnnt
The term stridor refers to audible respiratory noise edema a~~ erythei:na of the supraglottic strn ·turC'S
produced by turbulent airflow through an obstructed compronusmg the airway. IV, cefotaximc or cd tri.1xonc
upper airway. It should be differentiated from stertor that are administered for 7 days.
refers to snoring-like noise produced from obstructed
nasopharynx or oropharynx.
X-ray of chest or lateral neck m ay suggest retro-
1
pharyngeal abscess, epiglottitis, croup or tracheal stenosis.
Computed tomography may be required to rule out
extrinsic vascular compression, but is rarely required in
an acute scenario. Flexible endoscopy h elps assess nasal
cavity, nasopharynx, oropharynx, supraglottis and glottis
during dynamic respiration without need for general
anesthesia, but is avoided, if acute epiglottitis is suspected.
Rigid la ryngotracheobronchoscopy, perform ed under
general anesthesia, is the gold standard when evaluating
a child with stridor. Apart from enabling diagnosis, it may
be therapeutic, allowing removal of foreign body, release
of a web or excision of papilloma. Common etiologies of
airway obstruction and stridor are discussed below. Fig. 14.10: Laryngotrac heobronc httls (c roup). 'Steeple sign'
1369 -
Bacterialchildr
trac11eitis typically caused b y 5 . aureus, affects endotracheal intubation. A snugly fitting endotracheal
youn?er ~and follows a viral upper respiratory tract tube may cause mucosa! trauma and inflammation in the
jnfecti~n. The ~d appe~ toxic and has brassy cough with subglottis, the narrowest part of the larynx leading to
biphasic or expiratory Stridor. X-ray neck shows an irregular scarring. Patients present with progressive biphasic strider
tracheal wall. Bronchoscopy is di agnos ti. c an d a 11ows a few days after extubation. Minor stenosis requires careful
culture and removal of purulent tracheal secretions. observation; severe stenosis requires release of stenosis
Retroph~n1ngeal ab~c_ess is a suppurative complication with C02 laser and dilatation, widening with cartilage
of bact:nal _pharyngitis or dental infection, with abscess grafts or excision of stenotic segment, with tracheotomy.
forIIlation m lymph nodes between the pharynx and Special T-shaped silicone tracheostomy tubes are used for
prevertebral f~scia. Patients appear toxic with high fever, temporary stenting until complete healing. If prolonged
strido_r, d_roolmg and. reduced neck mobility. Spread of inubation is expected, early tracheotomy prevents the
jnfecti~n mto the mediastinum can be fatal. The diagnosis complication of post-intubation subglottic stenosis. The
is confirmed by late~al neck radiograph and contrast CT. use of cuffed tracheostomy tubes should be avoided in
M~gement compnses parenteral antibiotics and surgical children; if a cuffed tube is essential, intermittent deflation
drainage of abscess by transoral or transcervical approach. is advised.
Tracheotomy may be necessary to secure the airway. Another complication of prolonged intubation is
laryngeal granuloma, typically located in the posterior part
congenital Causes of the vocal cord. Small granulomas cause hoarseness
Laryngomalacia is ~e most frequent congenital laryngeal while large lesions present with breathing difficulty. They
anomaly ~d ~e chief cau~e of chronic stridor in infancy. are diagnosed by endoscopy and amenable to endoscopic
The condition 15 characterized by inspiratory strider that removal.
increases when the child is supine or crying, and decreases
Foreign Body Aspiration
in a prone position. Flexible endoscopy reveals omega-
shaped epiglottis, short aryepiglottic folds and partial Foreign body aspiration should always be considered in
collapse of a flaccid supraglottic airway with inspiration. children presenting with acute onset strider and airway
Laryngomalacia is generally benign and self-limited, with obstruction (Fig. 14.11). If a foreign body is not expelled
most cases resolving by 18 months of age. Concomitant by coughing, it migrates into the low er airway lodging
gastroesophageal reflux should be managed medically. most commonly in the subglottis, the narrowest lumen in
Surgical intervention, in form of supraglottoplasty or the ainvay leading to breathing difficulty. Objects such
temporary tracheostomy, is advised, if respiratory distress as balloons pose the greatest risk of choking to death,
is significant. followed by round objects such as balls or marbles. Rigid
bronchoscopy and remov al of fo reign body by an
Vocal cord paralysis is the second most common experienced surgeon is urgently required. Small foreign
congenital laryngeal anomaly. Bilateral vocal cord
paralysis presents with high-pitched inspiratory strider
and cyanosis. It is usually caused by palsy of the recurrent
laryngeal nerve due to excessive stretching of the neck
during vaginal delivery. The condition may be idiopathic
or associated with Arnold-Chia ri malformation,
hydrocephalus or hypoxia. Unilateral vocal cord paralysis,
in contrast, presents with mild strider or weak cry.
Aspiration may occur, if cord immobility is due to vagus ....
nerve paralysis, as the superior laryngeal nerve (that
carries laryngeal mucosa! sensation) is also affected.
Iatrogenic injury to the left recurrent laryngeal nerve
during ligation of patent ductus arteriosus may be a ca~e.
Diagnosis is made on fiberoptic laryngosc_opy, w_h_ich
reveals bilateral or unilateral vocal cord immobility.
Unilateral cord palsy without aspiration does _not need
active treatment in most cases as hoarseness improves
":ith time. Tracheotomy might be required to secure the
airway in bilateral cord paralysis.
lotrogen/o Causes
Acquired subglottic stenosis is the most common cause Fig. 14. 11 : Foreign body, broken part of tracheostomy tube. in
of acquired strider, and usually follows long-term the lower trachea and left main bronchus
Essential Pediatrics
~
- 370
.
. h by endoscopy or usmg transcerv·
bodies mny lodge in sccondnry bronchioles <lnd present repair, e1t er tca1
later with pneumonin. Mnnagcmcnl comprises of approach.
bronchoscopy for foreign body rcmovnl, lavage and
physiothernpy lo clcnr up secretions and antibiotics. Suggested Reading
. gsworth A Thompson T, et al ManagPTh.....
Occnsionally, thorncotomy mny be required for foreign • Bagwell T, Ho II in • . th I -·· ..ut Of
. h erg enc}' department. e ro e of multid
bodies that cannot be retrieved cndoscopically. roup in I e e m C 20 01t
c . . hrine. Pediatr Emerg are 17; doi: 10]"'..:
ncbullzcd cpinep - V11/
C 0()()0000000001276. .
Tracheostomy pE · La ghan ML ~tanagement of airway obs tniction
• Marchese A, n . Med p .., il.iitl
The requirement of prolonged vcntilatory support, stridor in pediatric patients. Pediatr Emerg. ract .2011; H:l-2t
Blackmore K, Aood L\1. Laryngomalaaa: Is there
neurologic dysfunction causing aspiration, and need for • McCa ffer C' I Ot I 20 - ~
evidence base for management? J Laryngo o 11; 131:9.;o..)l
pulmonary toileting are indications for tracheostomy.
Caretakers should be explained about the implications of
tracheostomy, including the inability of patients to ~D~ISEA~S~ES~O~F~TH~E~S~Al~W.
~AR~Y~G=-==-LAN~D_S~~~~----
vocalize and the cure required. Tracheostomy is performed Infections
under general anesthesia with mechanical ventilation Bacterial parotid sialoadeniti.s is fre~uent in young
provided through an endotracheal tube or laryngeal mask. children and presents with painful urnlateral parotid
The trachea is opened at the level of the third or fourth swelling. Purulent material can .be expressed intraorally
ring by a vertical incision that is kept patent using two from the parotid duct upon paro~d m~sage. Management
non-absorbable sutures placed on either side of the involves oral antibiotics, hydration, s1alogogues, parotid
incision. Usually, an uncuffed tracheostomy tube is placed gland massage and warm compresses.
in children unless there is concern of aspiration, in which
case a cuffed tube may be used. Care after tracheotomy Mumps: Patients usually present with bilateral painful
includes repeated suctioning to maintain patency, change parotid enlargement and mild fever, and rarely, with acute
of tube every 5-7 days, chest physiotherapy and peri- unilateral hearing loss or vestibular weakness. Therapy
stomal skin care. When tracheostomy is performed in comprises adequate hydration and analgesics.
infancy and kept for long, speech and language Tuberculosis may affect the parotid or other salinry
development may be delayed or impaired. glands with or without lung involvement. Sarcoidosis may
present with unilateral or bilateral parotid swelling, along
Hoarseness systemic symptoms and peripheral lymphadenopathy.
Vocal nodules are the chief cause of hoarseness in children. HIV infection commonly involves the parotid glands,
Caused by vocal abuse, these are seen most often in presenting as bilateral intraglandular cysts that recur after
children who scream habitually. The severity of needle aspiration.
hoarseness fluctuates, worsening with vocal abuse and
improving with rest. Endoscopy reveals small, bilateral, Drooling
opposing nodules at the junction of anterior and middle- Drooling (sialorrhea) is common in infancy but persists
thirds of the vocal cord. Speech therapy is advised; surgery beyond 2-3 years in children with neu romuscul.u
is rarely indicated. disorders and in mouth breathers. Common cause:> of
Reflux is implicated in occurrence of laryngitis, subglottic drooling are dental malocclusion, adenoid hypertrophy,
stenosis, chronic sinusitis and otitis media with effusion. cerebral palsy ~nd lip incompetency. Chronic drooli~g
Diagnosis is established with 24-hour pH monitoring. :nay l~ad to sk11: excoriation, d yselectroly temia, soetal
Patients respond to lifestyle changes and use of proton isolat10n, learning difficulties and, in sever~ c.1ses.
pump inhibitors; fundoplication is required in severe cases. aspiration pneumonia. Initial treatment is conservath·e
Hypothyroid myxedema may occasionally cause vocal fold and includes correcting the posture, orodental rehabilita·
15
Disorders of Respiratory System
Su11hll K Kabra
DEVELOPMENTAL PHYSIOLOGY higher initially, bt>causL' nf low com pl lnnni of 1lw 1wwhorn
At birth, the newborn has to contend "·ith sudden lung ( 1.5 mL/ cm H~O at bl rth). 'l'lw corn pl lilll<'(' lr' c rl'<'i ~C!~
transition from fetal life to extra uterine exisren~. During in the first few lu1ms ((1 (1 mI./ cm 11:.0 n11d r1·1il 11lnnc<· lo
fetal life, the placenta helps in the gas exchange. Therdore, air flow dl'c.:t·easl's. The tidal volunw o( ,, :1 kg l11font Is
fetal oxygen tension remains constant, independent of the approximately l6 mL ,,t 28 bn•,1ths pl'r rnlrHttl•, R1•!-J llng
matemal le\·els of oxygen. Prior to :!8-32 weeks, the lungs lung \'Olume gradually iricrl'.lSL'S In till' first ft•w hour!:! lo
ha\'e an inherent tendency to collapse and .u-e tmable to rcac.h a mnximum Llf Hll mL \Vlthin 211 hours.
retain any air. The surfactant, a protein in the ~n.~br lining G11s t'.\·c/umgt• ;,, m·wliom: Tlw normnl 11cwl)()rn require!:!
layer decreases the akeolar surface tension and imparts about 7 mL of uxygl'n/mi nute/kg, which is nlrnosl twice
finite elasticity to the interface. As a result, less pressure is the rt?quirement of .m ndult based 011 rclntivc weight.
needed to distend the lungs. When the lung is inflated from Oxygen uptake is a complex prol·css involving lrnnsport
a small or negligible volume such as in atelectasis or from across the alwol.n c.lpillnry mcrnlmnw (diffusion). Tht!
a situation when the alveoli are filled \\ith liquid as happens dead space in llL'Wborn is about 2 ml./ kg with resting tidal
during the first breath at birth, lesser force is required to \'olumc being:!() ml; 35% of the breath is wasted Ml
open up the alveoli, if there is low surface tension at the comp.ucd to 30% in the ndults. Persisting fl•tnl chnnncl[ol
air-liquid interface and if the radius of the terminal units and the ventilation perfusion problems lcncl to incrcnsc
of the lung is adequate. Although surfactant can be in the right-to-left shunt.
detected in the lung exudate from human fetuses as early Gns trnttsport: Rdati\'c hypoxia inn newborn is corrcctcc.J
as 24 weeks, the quantity increases greatly towards the in 5 minutes, hypercapnia by 20 minutes nnd ncidosis in
end of term gestation. Its deficiency leads to respiratory 24 hours. The initi<ll nddosis is partly mctnbolic, due to
distress syndrome. high blood il'vcls of lncta tL•. The higher hemoglobin
Gas transport iti fetal life: Carbon dioxide tension falls concentration and shift lo the left of tlw oxygen
from 35 mm Hg at 10th week of gestation to 28 mm Hg at dissocintion curve allows the newborn to carry higher
full term. The difference in oxygen dissociation cul'\"eS and concentration of oxygen than the <ldult.
increase in hemoglobin concentration enable the fetus to
carry out effective oxygenation of the tissues. TI1e affinity Mechanical Function throughout Childhood
of hemoglobin for oxygen is increased in the presence of The total Jung capacity in« newborn is 150 mL compared
2,3 diphosphoglycerate (2,3 DPG). However, fetal hemo- to -5000 mL in adults. With growth of lungs, there is
globin is relatively insensitive to the effect of 2,3 DPG. multiplication of alveoli and increase in the size of nlveoli
Theuptakeofcarbondioxidealsoshiftstheoxygendissoda- and airways. Pores of Kohn or intcrnlvcolar comrminica-
tion curve to the right; thus adequate oxygen delivery is tions also develop with irKr(•asing age. There is n lnrgc
ensured by the high tissue levels of carbon dioxide. increase in compliance and fall in resistance. The rcciprocnl
Onset of respiration: Hypoxia, hypercapnia and increased of resistance, i.e. condudoncc, rises in proportion lo the
sensitivity of chemoreceptors are the main factors increase in lung volumes. Increase in minute ventilation
responsible for initiation of respiration at birth. reflects the incre\lse in the metabolic rate. De<ld space, tidal
.,.. volume and change in frel1uency reflect changes in the
iveonatal respiratory function: Before birth, the 1ungs are
filled with fluid that needs to be replaced by air. Some mechanics of the lungs.
fluid is extruded from the mouth and some is absorbed Gns tra11sport: The rise of pl l \Ind pC02 together means
by the lymphatics. Intrapleural negative pressure required that the buffer b«se of the blood nl!;o incrcnscs. Bicarbonntc
for the first breath is 40 to 100 cm H 20. This pressure is rises from 19 mEq/L at 2-y<.'nr to -24 mEq/L at 16-ycnr of
371
....... .
II 372 I ~~~~~~~~~~~=Es~s~e~nt~la~l~P~ed~la~t~rlc=s'...-~~------~~~~~--~
. lung disease: Bronchiectasis, cystic fibrosis·
age. Arterial pa02 is -75 mm Hg in the newborn period • Suppura t1ve . hi
and around 5-year reaches adult levels of 95 mm Hg. .
• Fore1gn body retained in bronc
.
• C ongen1't a 1 malformations, sequestrated lobe,
Suggested Reading bronchomalacia .. . .
• Warburton D. Overview of lung development in the newborn • Immune deficiency, primary c1liary dyskin~s1a
humnn. Neonatology 2017; 111:398-401. • Anatomic lesions: Tumors, tracheal stenos1s, H~type
tracheoesophageal fistula
COMMON RESPIRATORY SYMPTOMS
• Psychogenic, habit cou~h ..
Cough • Post-nasal discharge, sinusitis
After maximal inspiration, air is suddenly released • Gastroesophageal reflux disease
through the partially closed glottis, because of forceful • Interstitial lung disease
contraction of the expiratory muscles. This produces a
bout of cough. The cough reflex is controlled by a center Expectoration
in the medulla. Irritation of the pharynx, larynx, trachea, Children have difficulty in expectorating, and hence
bronchi and pleura is transmitted by afferent impulses swallow respiratory secretions. ?lder children ~ith
through the vagus or glossopharyngeal nerves. Efferent chronic respiratory problems may bnng out e~pect?ration.
pathways relay to the larynx and respiratory muscles. Common causes of significant expectoration mclude
Cough is an important defense mechanism that helps bronchiectasis, lung abscess, bronchitis, asthma, and
remove infected secretions from the trachea and bronchi. tuberculosis. The amount and nature of expectoration may
Cough should not be suppressed in young children as give clue about the etiology. Investigations such as cell
retention of secretions may cause atelectasis and count, Gram stain and culture or stain for AFB and culture
pulmonary complications. On the other hand, persistent help in diagnosis and guiding treatment.
cough interferes with sleep and feeding. It fatigues the
child and may result in vomiting. Hemoptysls
Hemoptysis is defined as blood-stained expectoration.
Causes of Acute Cough Causes of hemoptysis may be necrotizing pneumonia,
• Upper respiratory tract infection. Common cold, foreign body aspiration, bleeding diathesis, cavitatory
postnasal discharge due to sinusitis, hypertrophied tuberculosis, idiopathic pulmonary hemosiderosis, mitral
tonsils and adenoids, pharyngitis, laryngitis and stenosis, dilated cardiomyopathy, Goodpasture syndrome
tracheobronchi tis and small vessel vasculitis.
• Nasobronchial allergy and asthma
Respiratory Sounds
• Bronchiolitis, pneumonia, and pulmonary abscess;
empyema Sounds originating from the respiratory system may be
• Measles heard with or without a stethoscope (Table 15.1). The
• Whooping cough intensity and pitch of these sounds vary based on their site
of origin within the respiratory tract, the dictum being that
• Foreign body in air passages the pitch increases and the intensity decreases as one goes
lower into the respiratory tract. Snoring is a loud but low·
Causes of Chronic and Recurrent Cough
pitched ~o~d b~ause it results from the oropharynx, while
• Inflammaton; disorders of airway: Asthma and Loeffler wheeze is high pitched and less intense since it originates
syndrome from the lower tract. Generally, extrathoracic airway
• Infection: Viral, bacterial, chlamydia, mycoplasma, ob~truc~ion produces inspiratory sounds, intrathoracic
tuberculosis, parasitic ma1or arrway produces inspiratory as well as expiratory
• Inhalation of environmental irritants such as tobacco sounds and distal airway obstruction produces
smoke, dust predominantly expiratory sounds.
Oropharyngeal obstruction
.
~_,J ... .. • • -
Character
-: - .._
- •
.· ,
c':' Table 15•2: Distinguishing betWeen. stridor due to 'supraglottlc and tracheal obstructio~
-~ II
II
- I
I
include: (i) systemic hypertension, (ii) blood dyscrasia iontophoresis. In normal children sweat chloride values
1
(coagulation, bleeding disorders), and (iii) p ertussis. are <40 rnEq/ L; level more than 60 rnEq/ L is seen in cystic
fibrosis. Values between 40 and 60 mEq/L are borderline
Treatment: Pressure on alae nasi for 10 minutes controls
and need to be repeated.
bleeding in most cases. In resistant cases, the nasal mucosa
is plugged with gauze piece socked in 1:10,000 solution Suggested Reading
of adrenaline hydrochloride as a temporary measure.
• Beydon N, Davis SD, Lombardi E, et al. An official America~
Profuse bleeding is more likely to arise posteriorly, from Th or acic Society / European Respira tory Society staternen~·
the sphenopalatine vessels. Firm anterior and posterior . t . . . er1t
Pulmonary f trnction estmg m preschool children. Am J Respil"
p acking is done. Care Med 2007; 175:1304-45.
Disorders of Respiratory System
375 -
• Miller .A. E~right PL. PFT lnterprelivc strntcglcs: Am crlcn n Co11gli symps supprcsA cough and retention of mucoid
Thoracic Society /Europenn Respirntory Soclcly 2005 guideline
gaps. Rcspir Cnrc 2012; 57:127-33.
secretions that predispose lo 11pasmodic cough, wheezing,
• Nicolai T. The role of rigid and flexible bronchoscopy in chi ldren. atelcctasis and s uppuration . These agents should be
Pediatr Respir Rev 2011; 12:190-5. avoided in infants and young children.
Antibiotics ;ire of Jillie value in virnl infections. These arc
UPPER RESPIRATORY TRACT INFECTIONS used, if Lhc secretions become purulcnl, lhe fever continuc..-s
Nasopharyngltls (Common Cold) lo rise nnd if the child develops bronchopneumonia.
Common cold is the most frequent illness in childhood Nursing care includes protecting from sudden exposure
~aused by ader:oviruses, influenza, rhinovirus, para~ to chills. Pceding should be conlinucd to maintain hydration.
influenza o~ resp~ratory syncytial viruses. These arc spread
Acute Tonslllopharyngltls (Sore Throat)
by dropl~t mfechon. Predisposing factors include chilling,
sudden exposure to cold air, and overcrowding. Rhinitis Acute inflammation of the pharynx and tons ils is usually
could also be due to allergy. caused by viral infections such as adcnovirus, influenza,
parninfluenza, entcrovirus and Ebstcin-Barr virus. ft may
Clinical Features nlso be caused by measles, rubella, Streptococws pyogenes
especially group A ~-hemolytic streptococci, Mycoplasma
These include fever, thin nasal discharge and irritability
pneumoniae and Candida albicans.
Cervica~ lymph nodes may enlarge. Nasopharyngeai
c~ngeshon cau~es nasal obstruction and respiratory Cllnlcal Features
distress. Eust~c~ian tu~e opening may be blocked leading
to serous ohtts media and congestion of tympanic Fever, malaise, h eadache, nausea and sore throat are
membrane. In allergic rhinitis, there is a clear mucoid characteristic. It is difficult to distinguish clinical
discharge with sneezing. There is no contact with an syndromes due to viral or s treptococcal infections.
infecte~ patient and history of allergy is usually present.
Hoarseness, cough and rhiniti s are common in viral
Wheezing may occur in a significant proportion of cases. infection. Jn these, the onset is gradual and there is less
toxemia. In streptococcal infections, cervical Lymph nodes
Narrowing of the airway and pharyngeal irritation
are enlarged and illness is more acute with high fever,
causes dry hacking cough. Excessive lacrimation is due
exudates over tonsillar s urface and absence of nasal
to the blocked lacrimal ducts in the nose. Nasal discharge
discharge or conjunctivitis. Young children may not
may become purulent, if secondarily infected. The illness
complain of sore throat, but refuse to feed norma lly.
usually lasts for 2-3 days but cold may persist up to two
weeks. Compllcotlons
Compf/cations The illness may be complicated in the acute stage by otitis
media, sinusitis, and peritonsillar and retropharyngeal
Otitis media, l aryngitis, sinusitis, bronchiolitis,
abscesses . The infection may sp read down the
bronchopneumonia and exacerbation of asthma.
tracheobronchial tree and cause tracheobronchitis and
pneumonia. Streptococcal sore throat may be followed a
Differential Diagnosis
few days later by immune-mediated conditions, presenting
Nasal foreign body may present with unilateral with acute rheumatic fever and acute glomerulonephritis.
serosanguineous or purulent discharge from nose.
Diagnosis
Snuffles is clear mucoid discharge from the nose in the
first few weeks of life. Snuffles of congenital syphilis is The possibility of pharyngitis due to group A beta-
hemolytic streptococci should be considered in patient
rare and causes bilateral serosanguineous discharge
presenting with fever, exudates in throat, tender enlarged
commonly excoriating the upper lip and leaving fine scars.
cervical nodes and absent nasal or conjunctiva) congestion.
t:Jasal strictures may ulcerate leaving a flat nasal bridge.
Throat culture for group A ~-hemolytic streptococci helps
Treatment in d efinitive diagnosis. Neutrophil count is often elevated.
Rapid diagnostic tests for P-hemolytic streptococci are not
Relieve nasal congestion: Nose drops of saline may give frequently available.
symptoma tic relief. Nasal decongestants (ephedrine,
xylomatozoline) may cause rebound congestion and Different/al Diagnosis
should be avoided. Antihistaminics dry up thin secretions
Herpangina is an acute febrile illness caused by group A
and relieve sneezing but sh ould be avoided in the first
6 months of life. Newer non-sedating agents (loratidine, Coxsackievirus. Patients have dysphagia, sore throat and
papulovesicular lesions surrounded by erythema over the
cetirizine) are useful in allergic rhinitis.
tongue, pharynx, anterior tonsillar pillars and soft palate.
F . . .
ever is controlled by antipyretics such as paracetamol. Pharynx appears congested.
11111 370 I --------~--~---------=E~ae~e~n~tl~el~P~o~d~le~tr~lc~s~------------~~~~---
VIJ1lltltt'l'lt1 ltt chnrrwtNizcid hy modcrlllP grndc fever,
ri h'
• C11iwy JH, { c
hero ME. Meta analysis of short
IC
course~
p A streptococcal tonsillopharyngitis. p~?'ic
lrl'atmcnt or grou ""%
11uvcJ1·0 tmwm ltt, rmrn th ri 111i11111 I nwmhrimc~ forma lion over rnfoct Dls J 2005; 24:909-17. . I ML A ihls '
tho frur''"ti or pnlnl<l. Thu dlflHllORIH IH conflrmi!d by ur81mt Al Saraswat A, van Dne . nt tarnines fo
r1111l'11r cxn mlnntlon from throat 11wnb. • De Suiter ·Id' Cochrane Database Syst Rev 2015; ll:CT"lnM...~.lht
common co · -vv7.)'!).
1
coccal infections. The procedure may be recommended in
children with multiple episodes of tonsilfitis or in case of bc:come manifest. The child becomes restless and arixioUS
tonsiJJarorpcritonsH/arabsa.-ss. It may reduce the incidence with ta~hypnea due to increasing hypoxemia. Eventually
of group A beta-hemolytic streptococcal infection. cyanosJS appears. As obstruction worsens breath sounds
are inaudible and stridor may apparently' decrease.
Suggested Reading
Spasmodic Croup
• Alvt-s Calv3o MC, P.1>Cha Cri.11pinn Santl>s MA, Alvt>s da Cunha
AJ. AntlblnH~ for pn:vt'ntln~ ~uppurative complication.s from It occu.rs in ~hildren between the age of 1 and 3 years·
tmdlffortmllatcd acute n.~plratory infoctlonti in children under five There 1s at tm~es no preceding coryza. The child wa~eS
year# of axe. CAichran1.: OatJ.ibaMt Syst Rev 2016; 2:CD007880. up suddenly m the early hours of the morning with
Disorders of Respiratory System 377 .
Pneumococcaf Pneumonia
Respiratory infections due to S . prrt·11111011ine are transmitted
by droplets and nre common in winter months. Over-
crowding nnd reduced host resistance predisposes the
children to infection with pneumococci. Bacteria multiply
in the alveoli, resulting in an inflammatory exudate.
Scattered areas of consolidation occur that coalesce nround
bronchi and later become lobular or lobnr in distribution.
The incubation period is 1 to 3 days. The onset is abrupt
with headache, chills, cough and high fever. Cough is
initially dry but may be associated with thick msty sputum.
Child may develop chest pain that is occasionally referred
to the shoulder or abdomen. Respiration is rapid. In severe
cases, there may be gnmting, chest indrawing, difficulty in
~ee~in? ~d cyanosis. P~ret~ssion note is impaired, air entry Fig. 15.2: X-rcry chest showing staphylococcal pneumonia. Note
is dmurnshed, and crep1tations and bronchial breathing is consolidation in both lung fields with pneumotocoeles (arro·1~
heard over areas of consolidation. Bronchophony and
whispering pectoriloquy may be observed. Meningismus fibrosis or follow staphylococcal pyodenna. Debilitating
may be present in apical pneumonia. conditions including malnutrition, diabetes mellitus and
macrophage dysfunction also predispose to infection with
The diagnosis is made on history, examination, X-ray
findings of lobar consolidation (Fig. 15.1) and leukocytosis. staphylococci.
Bacteriological confirmation is difficult but sputum may In infants, the pneumonic process is diffuse initially,
be examined by Gram staining and culture. Blood culture but soon the lesions suppurate resulting in broncho-
may be positive in 5-10% cases. Demonstration of alveolar destruction. Multiple microabscesses are formed,
polysaccharide antigen in urine and blood is not specific which erode the bronchial wall and discharge their
for pneumonia, since it may be positive in patients with contents in the bronchi. Air enters the abscess ca\·itv
colonization in throat. during inspiration; progressiv e inflation results ifl
Penicillin G 50000 IU/kg/day is given IV or IM in formation of pneumatoceles that are pathognomonic of
divided doses for 7 days. Therapy with IV cefotaxime, staphylococcal pneumonia (Fig. 15.2). Staphylococcal lung
ceftriaxone or coamoxiclav is equally effective. abscesses may erode into the pericardium causing
purulent pericarditis. Empyema below 2 years ofage is nearly
Staphylococcal Pneumonia always staphylococcal in etiology.
Staphylococcal pneumonia occurs in infancy and Pulmonary infection may be associated with
childhood. Pneumonia may be primary infection of the disseminated disease, with abscesses in joints, bone,
parenchyrna or secondary to staphylococcal septicemia. muscles, pericardium, liver, mastoid or brain. The
It may be a complication of measles, influenza and cystic ?iagnosis ~f staphylococcal pneumonia is suspe(ted in
mfants with pneumonia with features of svstemic
staphylococcal infection. Complications ~f pyo-
pneu~otho~ax and pericarditis are highly suggesti,·e of
the d1agnos1s.
The child is hospitalized. Fever is controlled with
antipyret~cs and. hydration is maintained by IV fluids.
Oxyge~ is a ?i:n1~1stered to relieve the d yspne.1 and
cyanos~s. Antib~o~1c .therapy should be prompt and carried
out with penic1lhn G, coamoxiclav , cloxacill in or
ce.ftriaxm~e . If t1.1e pat~ent does not respond, vancomycin,
te1coplanm or lmezohd may be used. Prolonged therapy
(2-6 weeks) is desirable.
Table 15:4: Children (2 moiiitis'io 5·ye_ars) with -co~gh or difficult breathi.ng: Facilitate' treatment decisions
Category Essential feat~res , Treatment category
Cough or cold No fast breathing; no indicators of severe pneumonia Home care; home remedy for cough;
paracetamol for fever
Pneumonia with or without Fast breathing: 2-12 months ~50/minute; Home care; oral amoxicillin
lower chest lndrawlng 1-5 years ~40/minute
Lower chest indrawing, normal saturation
.~evere pneumonia Lower chest indrawing; unable to drink or Inpatient care IM, IV benzylpenicillin or
breastfeed, convulsions, lethargy, unconsciousness, ampicillin and gentamicin
.severe respiratory distress, _central cyanosis
Disorders of Respiratory System j 381 -
Pathogenesis
Inflammation of the bronchiolar mucosa leads to edema
and bronchiolar spasm, thickening, forma tion of mucus
plugs and cellular debris. As airway resistance is inversely
related to the fourth power of the radius, even slight
narrowing causes marked increase in resistance and
reduced airflow. Resistance to airflow is increased both
during inspiration and expiration. During expiration, the Fig. 15.3: X-ray chest in a 1-year-old with acute bronchio lrns.
bronchioles are partially collapsed and, therefore, egress Note hyperlnflatlon on both sides and a few infiltrates
of air from the lungs is severely restricted during this
phase. This leads to trapping of the air inside the alveoli Several attacks occur in the same patient. Response to
causing emphysema. When obstruction is complete, the bronchodilators is more cons istent in children with
trapped air is absorbed resulting in atelectasis. Diminished asthma, compared to bronchiolitis.
ventilation and diffusion in severe bronchiolitis result in lleart failure: Conges tive heart failure is s uggested in
hypoxemia and respiratory acidosis. presence of cardiomegaly, tachycardia, enlarged liver,
raised JVP, edema and basal crcp itations.
Cllnlcal Features and Diagnosis
foreig n botlies: Thes e arc diagnosed by history of
The disease begins as an upper respiratory infection. After
aspiration of foreign body, localized wheeze and signs of
a few days, the child has high fever with rapid breathing
collapse or localized obstructive emphysema.
and respiratory distress. Those with severe disease show
retraction of lower intercostal spaces and supras tcrnal Bacteria/ pnettmonia: In bacterial pneumonia, the signs
notch. In severe infection, infants have respiratory distress of obstruction arc less pronounced, feve r is high and
and are cyanosed. Expiration is prolonged; fine crepita- adventitious sounds in lungs arc prominent.
tions and rhonchi are auscultated. Breath sounds arc faint
or inaudible in severe cases. As air is trapped in the lungs, Treatment
the liver and spleen are pushed down; anteroposterior Treatment of bronchiolitis is sympto matic. The child
diameter of the chest is increased and hyperresonancc is should be nursed in a humid atmosphere preferably in
noted on percussion. reclining pos ition al 300 to 40'' with head and neck
X-ray ches t shows hyperinflation and infiltrates clevntcd. lnfonts wilh mild disease can be cared for at
(Fig. 15.3). The diaphragm is pushed down and lung fields home in a humidified atmosphere. If respirato ry dis tress
appear abnormally translucent. The leukocyte count is increases or feeding problems appear, the patient should
normal or slightly elevated. A rapid test on naso- be hospitalized. Mois t oxygen inhalation is the mainstay
pharyngeal aspirate can identify the presence of RSV. of treatment, admini11lercd continuous ly even in absence
of cyanos is. Jlluids and electrolyte balance should be
Course and Prognosis maintained. Very sick infants may need a concentration
Bronchiolitis is generally a self-limited illness, with of 60% oxygen given through a hood, to maintain oxygen
symptoms subsiding in 3-7 days. Death may occur, due saturation more than 92%.
to respiratory failure, in one percent of severely ill patients. Antibiotics have no role. Ribavirin, an antiviral agent,
:11'e relationship of acute bronchiolitis to bronchial asthma has no role In the treatment of in fonts who were previously
in later life is seen in about one-fourth of cases. healthy. f fowcvcr, the mcc.Jic;ition i.hortens the course of
lllnc1m in infants with underlying congenital hea rt disease,
Differential Diagnosis chronic hmg disease and immunodeficiency. Hibavirin is
Bronchial asthma: Bronchial asthma is unusual below the delivered by a ncbulizcr l 6 hours a d<iy for 3-5 days in
age of 1 year. There is often a family history of asthma. such CtlHCB.
-382 I ~~--~~~~------...::.::=..:.:.:.:=!..!:!~~'..-------------~~------~
Eaaontlnl Podlatrlc•
-
Bronchodilntors, inhaled or svst~mk sll.'l'Ulds nnd (II) l'Uluniw of 11 trborn o nll crgcn,11 In atmo~phern th.~t
epinephrine h,we not bL'l.'n found ·u~dul In lnfo nl!:l with uxocl!rbnlu nHlhmn.
acute bronchiolitis. lf a patient shows hup1·u\'l.1l\\l'llt with
1;1110 1/mi s: Slrc1:111, th rou~h lhe vagu8 nerve, may initiiitJ.
bronch~il,\tor or~pincphdnc, fmthcr dusc~ l\ll))' be glvl't\
bmnchlnl Mmooth mu11clc com1lrlctlon. •
e\-ety 4-6 hours. lnh,llcd. hypcrtonk :;,,\inc h1\s bct'I\ shown
to be effu<:tiw in a subgroup of paticnt$. Its rnullnu llSl.' Is l ·'ood: Atlurgy to food protcln1J or additives ha, an
not reconunended. Continuous poslti\'c ,\hwny prcssu1·c ln8lgnlflcnnl role In pnlhogcncfllEJ of asthma.
(CP.~P) or ."~sisted Yentil.\tion is rcquircd lu m1mnge
~sprral'?~' !mlure. Extracorporeal membrtHW oxygl.'nnllon li111foalm•: Children may get lncrcMc In symptoms during
is effectiYe m se\·ere cases. puberty.
Suggested Reading Clinical Features
• Os\·ald CE, CJ..uke JR. NICE dinic;ll guiddim~: lm11\d1\olltls In Thu clinlcnl fcnturc~ of n8thmll
vary from rccurrc'tlt cough
children. Arch Dis Child Educ Pr.let Ed W16; 101:.\6-8. to severe wheezing; symptomfl occur with change in
• \\ alsh P, Rothenberg SJ. American Academy of Pclll"tr\cs 201-1 senson nnd nrc aggrnvatcd by exercise and more in nigh~.
bro~chio~~tis guidduws: bonfire of the evidl'l\c~. \Vest J Emcrg Med Acute asthnrn 1nay uAunlly begin with a cold or bouts of
20b; 16:S5-S.
spasmodic coughing more so llt night. Jn early phase of
the nttnck, cough is non-productive. The patient is
BRONCHIAL ASTHMA dyspncic, with prolonged expiration and wheezing. With
Bronchia~ asthma is a disease characterized by incn~ased. incrensing severity, accessory muscles of respiration are
responsiveness of the airways to v nrious stimuli. used. The child sweats profrn;cly and is apprehensive and
Widespread narrowing of the airways cm1ses paroxysmal restless.
dyspnea, wheezing or cough. The diffuse obstruction to In severe episodes, the child shows air hunger and
the airflow is re,·ersible in a large majority of cases, either fatigue. The presence of cyanosis, pulsus paradoxus and
spontaneously or in response to treatment. cardiac nrrhythrnias indicates severe illness. The chest is
hyperresonant because of air trapping. Occlusion of
Pathophyslology bronchi by mucus plugs mny result in collapse of small
Diffuse airway obstruction in as thma is caused by segments of the lung. /\s obstruction becomes severe, the
(i) edema and inflammation of mucous membrane lining nirflow decreases markedly and breath sounds are feeble.
the airways, (ii) excessive secretion of mucus, inflamma- Wheezing which was earlier nudible may disappear. Thus
tory cells and cellular debris, and (iii} spasm of the smooth absenc~ of wheezing in presence of cyanosis and respira-
muscle of bronchi. tory. d1st~e~s does not suggest clinical improvement.
Asthma has been classified as atopic (earlier called Durmg chntcal recovery, airflow increases and wheezing
may reappear.
extrinsic; IgE mediated, triggered by allergens), non-
atopic (earlier called intrinsic; non-IgE mediated, triggered Persistence of hyperinflation of the chest even after
by infection), mixed, exercise induced or aspirin induced. su~sidence of an acute episode signifies that the appJrent
Inhalation of an allergen leads to a biphasic response with rehef from bronchospasm will be short lived. In chronic
early and late reactions ultimately causing broncho- intern:'ittent .cases, the chest becomes barrel shaped.
constriction. Clubbing of fmgers, however, is unusual.
Diagnosis
Triggers of Asthma
Infectio11s: Viral infections in young children are The diagnosis of asthma is clinical in most cases. Recurrent
important triggers of airway narrowing. Viral infections attacks .of wheezing. or spasmodic cough arc highly
might interfere with the integrity of mucosa} surface by s~1ggestl~e of bronchrnl asthma. Cough, which is asso·
opening up tight intraepithelial cell junctions, inducing ciated with asthma generally, worsens after exercise.
epithelial shedding. They also result in mucosa} edema Sputum is clear and mucoid, but might be yellow due to
I
large number of eosinophils.
and mucus secretion.
P!1lmo1~ary f1111cticm tests (PFT) are importan t for
Exercise: Exercise-induced asthma occurs in genetically
diagnosis of doubtful cnses and monitoring response to
susceptible individuals with hyperreactive airways
therapy. Import<mt parameters on spirometry inclu~e
because of evaporative water losses from the respiratory
PEFR, FEVl, FVC and FEV25-75, all being decreased in
tract. Water loss induces miicosal hyperosmolarity, which
nsthma. FEVl is commonly used for documenting the
stimulates mediator release from mast cells.
severity of nsthma. FEV25-75 is effort independent ~n~
Weather: Sudden change of weather may result in: more sensitive indicator of airway obstruction. PEF~ is
(i) evaporative water losses from lower airways; and measured with flow meter, while spirometry is required
Disorders of Respiratory System j383 -
for others. _Abnormalities in PEFR suggestive of asthma Cystic fibrosis presents with recurrent wheezing; patients
include: Diurnal variation of more than 20%, ~80% of show clubbing and malabsorption. X·ray chest shows
predicted, and improvement of ;:::20% after bronchodilator hyperinflation, peribronchial cuffing and pneumorua. The
therapy. diagnosis is made on sweat testing.
Absol~1te eo~i11opl1il co1111 ts might help distinguish allergic
Management of Asthma
from infectious nature of chronic respiratory disease.
When eosinophilia is present, the symptoms generally Broncliial asthma cannot be cured but can be controlled.
respond to antispasmodic therapy. Goals of therapy are: (i) maintain near normal pulmonary
Cl1es~ X-:ay film shows bilateral and symmetric air function; (ii) maintain near normal physical activity;
trapping m case of asthma. Patches of atelectasis due to (iii) prevent nighttime cough or wheezing with mirumal
mucus ph~gs are i:ot unusual. Main pulmonary artery may chronic symptoms; (iv) prevent recurrences; (v) avoid
be promi.nent m severe cases due to pulmonary adverse effects of therapy. Effective long-term manage-
hypertens10n. Bronchial cuffing may occur due to the ment of asthma involves three major areas:
presenc.e ?f edema fluid in perivascular and peribronchial i. Identification and elimination of exacerbating factors
mters~ih~l space. Extensive areas of collapse or ii. Pharmacological therapy
conso~1dahon should suggest an alternative diagnosis. iii. Education of patient and parents about nature of
Occasionally, the chest radiograph may be normal. disease and steps to avoid acute exacerbation
Allergy tests. ~e.g. skin test, RAST radioallergosorbent Identify and Eliminate Exacerbating Factors
allergen s?ecif~c lg~) have limited usefulness. Blood IgE
may be raised m children with a topic asthma, but cannot Factors associated with development and precipitation of
be u~e.d ~s dia~ostic test. The role of skin tests to identify asthma are passive smoking, associated allergic disorders,
sensitivity to different antigens, and desensitization is inadequate ventilation at home with dampness, cold air,
limited. cold food, smoke, dust and pets in the family. Acute viral
respiratory infections are one of the chief causes of
Differential Diagnosis exacerbation.
Following measures may help in reducing risk of
Bronchiolitis occurs within the first 2 years, usually within recurrences:
the first 6 months of life, usually in winter or spring.
i. The bedroom should be clean and free from dust. Wet
Generally, there is a single attack. Repeated attacks
mopping of the floor is encouraged.
indicate viral infection associated wheeze or multi-trigger
ii. Since heavy tapestry attracts dust, light plain cloth
wheeze or asthma. Hyperinflation of chest with scattered
sheets should be used as curtains in the child's
areas of infiltration may be seen in chest X-ray. Asthma
bedroom.
may start at any age; more than 3 episodes are usual and
iii. Periodic cleaning of carpets, stuffed furniture, loose
wheezing is prominent. Infants with bronchiolitis and
clothing and hangings, calendars and books.
atopic dermatitis, high IgE levels or family history of
iv. The child's bed should be made of licrht material and
allergy need follow up for later development of asthma. • 0
aired regularly.
Congenital malformations with obstruction (vascular v. Caressing of animal pets is discouraged, as the child
rings due to aberrant right subdavian artery or double may be sensitive to their fur.
aortic arch, bronchogenic cysts, tracheomalacia) should vi. It is usually not necessary to restrict the diet, since
be excluded in differential diagnosis. food allergy is not the cause in most cases.
Aspiration offoreign body may result in localized area of vii. Adolescent patients should refrain from smoking.
wheeze, hyperresonance and reduced air entry. A history viii. Exposure to stron g odors such as wet paint,
of foreign body aspiration may be forgotten. Most children disinfectants and smoke should be minimized.
have frequent infections in the lung. ix. The child should avoid attics or basements, especially
if unoccupied and closed.
Hypersensitivity pne11monitis may follow inhalation of
organic dust (molds, wood, cotton or fur dust, bird Pharmacotherapy
•
droppings, grain) or exposure to specific agents (epoxy
resins, PAS, sulfonamide, nitrofurantoin). Patients have Pharmacological therapy of bronchial asthma involves
fever, chills, dyspnea, malaise, aches and pain, rales agents that relax smooth muscle and dilate airways, and
(crackles) and weight loss. X-ray chest shows interstitial those that decrease inflammation. Medications for long-
pneumonia with prominent bronchial markings. Levels term treatment of asthma include bronchod ila tors,
of lgG antibodies to specific antigen are increased. Skin steroids, mast cell stabilizers, leukotriene modifiers and
test shows Arthus phenomenon with local hemorrhage, theophylline (Table 15.5).
edema and pain within 8 hours. The diagnosis is Bro11c110dilators: Commonly used short-acting broncho-
established on lung biopsy. dilators are adrenaline, terbutaline and salbutamol, all
- 384
having a quick onset of action. Adrenaline stimulates a reduces the risk for systemic adverse effects. Commonly
and both fJ receptors, with ensuing cardiac side effects. used inhaled steroids include beclomethasone, budesonide
Terbutaline and salbutamol are specific 132 agonist and and fluticasone; budesonide (BOS) and fluticasone are
hence, have less cardiac effects. While adrenaline is given considered superior to beclomethasone (BOP)- The chief
subcutaneously, the others can be given by oral, inhalation concern with long-term use of inhaled steroids is their
or parenteral route. Inhalation route is preferred because adverse effect on growth with 20% reduction in growth
of rapid onset of action and a few side effects. velocity reported in the first year. The growth velocity
administered orally; significant clinical improvement is Table 15.7: Assessment of risk of exacorbatlon In noar luturo
seen after 14 weeks of therapy.
Uncontrolled asthma symptoms
Leukotriene modifiers: Leukotriene inhibitors are useful One or more severo exacorbatlon requiring hoopllollzatlon In
for treatment of mild to moderate persistent asthma and previous year
exercise-induced asthma. These agents act either by Ever Intubated or PICU admlaslono
decreasing the synthesis of leukotrienes (zileuton) or by Start of the usual 'flare-up' season
antagonizing the receptors (montelukast and zafirlukast). Exposure: Tobacco smoke; Indoor or outdoor air pollutlon;
Montelukast and zafirlukast are approved for use in Indoor allergens
children with asthma; montelukast can be used in children Major psychological or socioeconomic problomo for child or
>1 year of age while zafirlukast >12 years. family
Poor adherence with controller medication, or lncorroct lnhalor
T11eopl1ylline: Theophylline has concentration-dependent
technique
effects. While the bronchodilator effect is by inhibition of
phosphodiesterase, the agent also has anti-inflammatory Co·morbldltles: Obesity, rhino-sinusitis, confirmed food allorgy
and immunomodulatory effects at therapeutic serum Assessment of risk of exaccrlrntions: Based on history,
concentration. Recent guidelines recommend theophylline children arc ilssessed for risk of exacerbations (Table 15.7).
as an alternative second-line therapy (combined with Appropriate treatment to children who arc nl ritlk of
glucocorticoids) in moderate persistent asthma in children exacerbation may help in prevention of exacerbation.
~years, as second-line therapy for mild persistent asthma
in older children and adults, and adjunctive therapy (for Selection of metlication: After assessment of control of
nocturnal symptoms) in moderate or severe persistent asthma and risk for exacerbation, antiasthma drugs arc
asthma. selected . Treatment of asthma according lo the asf'let>sment
is shown in Table 15.8.
Immunotl1erapy: This consists of administering grad~a.lly Infrequent episodes with no risk for exacerbation arc
increasing quantities of an allergen extract to? sens1ti.ve treated with salbutamol or tcrbutaline all and when
subject, so as to ameliorate symptoms associate? with required. The oral route is used, if inhalation is not possible
subsequent exposure to the causative allergen. This form for any reason. Children with infrequent episodes but
of therapy is considered occasionally in highly selected having risk foctor(s) for exacerbation, or children with clay
children who are sensitive to specific allergens, e.g. grass time symptoms >2 per week or nighttime Hymploms once
pollen, mites. Immunotherapy is carried out only under a month should be treated with low dose inhal<!d i;teroids
specialist supervision. with salbutamol inhalation, as and when requ ired. An
alternate strategy is montelukast or sustained rele;rnc
Phannacological management includes the ~?llowing key theophylline.
steps: (1) assessment of symptom control; (11) ass~ss~ent Children with troublesome symptoms on most days or
of risk of exacerbation; (iii) selection of me~1cahon; waking once a week or more, need low dose inhalation
(iv) selection of appropriate inhalation device; and steroids in 2 divided doses and long-acting fl-agonis t
(v) monitoring. (formoterol, salmcterol) above 12 years of age, and med ium
dose steroids below 12 years. Children with severe
Assessment of symptom control: Control of disease is uncontrolled symptoms need high dose inhalation Hteroids
graded based on frequency and severity of sympto~, and in divided doses and long-acting f~-agonists. Montelukast
functional impairment. This is assesse~ by askmg for can be used as add on treatment for belier control of
~equency of symptoms including daytime symptoms, symptoms. Persistent symptoms might require the use of
limitation of activity, nocturnal symptoms and need for low dose prednisolone, preferably on alternate days.
rescue medications, in past 4 weeks (Table 15.6), and
Selection of appropriate inhalation device: Drugs for
classifying as controlled, partially controlled and
maintenance treatment can be administered by inhalation
uncontrolled.
- 386 Essential Pediatrics
fig. 15.6: Aetered dose inhaler with spacer and face • Children <4-year-old: MDI with spacer with face mask
~ • Children >4-year-old: MDI with spacer preferred
• Children>12-year-old: MDI used directly. Use of spacer
improves drug deposition.
Step 3: Moderate persistent Daily use 132 agonist Low dose inhaled steroids +
Daily attack affects activity Long-acting 132 agonist OR .
Medium dose inhaled steroids
Step 2: Mild persistent Low grade symptoms twice a month Low dose inhaled steroids
Nighttime awakening once per month Short-acting 132 agonist, whenever
symptoms
Step 1: Intermittent Infrequent Short-acting 132 agonist, whenever
Asymptomatic and normal PEFR symptoms
between attack
require additional agents like short- and long-acting tration, use of spacer and potential harmful effects of
P-agonists or leukotriene modifiers. Short-acting drugs. Parents concerned about the use of steroids needs
P-agonists should be taken before going for exercise. Long- to be reassured that in conventional inhalation dosage,
acting P-agonists administered in the morriing show action the risk of serious illness outweighs the side effects of
throughout the day. Leukotriene modifiers are satisfactory medication. Peak flow monitoring done properly by
alternative to long-acting P-agonists. informed parents can help by:
Seasonal Asthma i. Detecting early deterioration in lung function
ii. Managing patients who have difficulty in sensing the
A proportion of children get symptoms of asthma for a brief
change in severity of airway obstruction
period in particular season. They remain asymptomatic for
the rest of the year. These children can receive maintenance iii. Managing patients whose asthma severity changes
treatment 2 weeks in advance. Medications are selected very rapidly
according to severity of asthma. After the season is over,
Home Treatment of Acute Exacerbation
patients are reexamined after discontinuing the medications.
The parent/patient is instructed regarding recognition
Newer Therapies and management of acute exacerbation of asthma at home.
A number of novel therapies have been examined for A written action plan is given. Acute exacerbation is
clinical use. Monoclonal antibodies against IgE identified by increase in cough, wheeze and breathless-
(omalizumab), IL4, ILS and IL13 may have promise as ness. PEFR, if measured, may be 15% lower from the
therapy for patients with refractory illness. baseline. For acute exacerbation, parents should ad.minister
short-acting P-agonists by MDI ± spacer ± facemask one
Education of Parents puff at a time repeated every 30-60 seconds up to a
Education of patients and their parents is an important maximum of 10 puffs with monitoring of syrnpt;ms. U
aspect of management. A description of the etiopatho- symptoms are relieved and PEFR is increased at end of
genesis of asthma in plain language should be made. The inhalation, the child can continue the p-agonists
spectrum of severity of the illness, likely course and (~a~butamol or .t~rbutaline) every 4-6 hours and pl~ a
satisfactory outcome is explained. Parents need to be :1s1t to the physlClan. If there is no improvement or partial
involved in the steps required to minimize exposure to rmpr?vement o~ symptoms of life threatening attack at
potential environmental triggers. Avoidance of all kinds any time, the child should be transferred to a hospital.
of smoke at home, including tobacco smoke, wood Patients with life-threatening asthma or those failing
burning and kerosene stove is emphasized. Parents should to show satisfactory response to inhalation therapy at
be advised regarding minimizing the use of carpets, home should receive a single dose of oral prednisolone
Suggested Reading
• Castellani C, Duff AJA, Bell SC, et al. ECFS best practice guidelines:
the 2018 revision. J Cyst Fibrosis 2018; 17:153-178.
• Manda! A, I<abra SK, Lodha R. Cystic fibrosis in India: Present,
past and future. ] Pulm Med Respir Res 2015; 1:002.
Diseases of the cardiovascular system are an important Table 16.1: Heart failure ·due to ·diastolic dysfunction
cause of childhood morbidity and mortality. The majority Mitra! or tricuspid valve stenosis*
of heart diseases presenting in early childhood a re
congenital, resulting from structural defects during Constrictive pericarditis
development. Rheumatic heart disease continues to be Restrictive cardiomyopathy
prevalent in India. Systemic hypertension is increasingly Acute ventricular volume overload (acute aortic or mitral
recognized in childhood and predisposes to cardiovascular valve regurgitation)
morbidity. A variety of other cardiovascular conditions Myocardial ischemia#
may present in childhood. The management of these Marked ventricular hypertrophy (hypertrophic cardio-myopathy,
patients requires an integrated approach with inputs from storage disorders, severe hypertension, severe aortic or
various specialties. pulmonary valve stenosis)
Dilated cardiomyopathy#
CONGESTIVE CARDIAC FAILURE
'Elevated atrial pressures with normal ventricular diastolic pressures
Congestive cardiac failure is the inability of the heart to •otten have combined systolic and diastolic dysfunction
maintain an output, at rest or during stress, necessary for
the metabolic needs of the body (systolic failure) and the
inability to receive blood into the ventricular cavities at
low pressure during diastole (diastolic failure). Thus, due Table 16.2: Causes of congestive cardiac failure
to systolic failure, it is unable to propel blood into the aorta Infants
and in diastolic failure it receives inadequate amount of Congenital heart disease
blood. Dias tolic heart failure is recognized by clinical Myocarditis and primary myocardial disease
features of heart failure and evidence of increased filling Tachyarrhythmias, bradyarrhythmias
pressures with preserved systolic function and in many Kawasaki disease with coronary occlusion
instances, cardiac output. An increase in left-sided Pulmonary hypertension (persistent pulmonary hypertension
pressures results in dyspnea from pulmonary congestion. of the newborn: primary pulmonary hypertension: hypoxia, e.g.
An increase in right-sided press ures results in upper airway obstruction)
hepatomegaly and edema. Besides hypertrophied Miscellaneous causes
ventricles, diastolic failure occurs in restrictive heart Anemia
disease and constrictive pericarditis. Hypoglycemia
Infections
Etiopathogenesls Hypocalcemia
The common causes of diastolic failure are indicated in Neonatal asphyxia (myocardial dysfunction, pulmonary
Table 16.1. While mitral and tricuspid valve stenoses result hypertension)
in elevated atrial pressure, they are not, in the strictest Children
sense diastolic heart failure. The causes of congestive
failure can be classified according to age (Table 16.2). Rheumatic fever, rheumatic heart disease
Rheumatic fever and rheumatic heart disease is typically Congenital heart disease complicated by anemia, infection or
endocarditis
encountered beyond 5 years age; its prevalence appears
Systemic hypertension
to be declining in selected urban populations. Heart failure
Myocarditis, primary myocardial disease
from congenital heart disease typically happens within
Pulmonary hypertension (primary, secondary)
the first 1-2 years of life. Patients with left-to-right shunts
394
--
Disorders of Cardiovascular System I 395 •
tend to develop CCF around 6 to 8 weeks of life. Unlike irritable ond crying oil the time. Often a mother mny stntc
Jeff to right shunts, congenital leakage of the mitral or the thnt the boby brcothc~ loo fost whlle feeding or that the
tricuspid valve can result in heart failure at ;,m early nge. baby is more comforlnblc nnd brcnthcs better when held
congenital tricuspid regurgitation (TR) manifests early ngninst the shoulder-which is lhe equivalent of
beCause the elevated pulmonary artery pressures increnses orthopncn in oldL•r children. Not infrequently, the baby is
its severity. If the TR is not severe, it may improve with brought wil'h persistent hoarse crying, whcc;i:ing,
tiIJle as pulmonary vascular resistance declines. excessive perspiration and less commonly, bccm1se of
The age of occurrence of heart failure may point facial puffiness (Table 16.4).
towards the underlying cause (Table 16.3). Heart failure
at an unexpectedly early age should prompt the search Signs
for an associated condition such as coarctation. Left-sided failure is indicnted by tachypnea and tachy-
Arrhythmias are an important cause of congestive cardia. Persistent cough, especially on lying down, hoarse
cardiac failure in infancy. Heart rates above 180/min tend cry and wheezing are other evidences of left-sided failure;
to precipitate heart failure. If the tachycardia persists for basal mies in the chest nre usunlly not audible. Right-sided
36 hours, about 20% will develop heart failure and almost failure is indicated by hepatomegnly and facial puffiness.
50% will do so in 48 hours. Any long-standing tachy- Examination of the neck veins in smnll babies is not
arrhythmia can be associated with ventricular dysfunction helpful. Firstly, it is difficult to evnluate the short neck
that may mimic cardiomyopathy. Typical examples include with bnby fat nnd secondly, 11emodynamic studies show
ectopic atrial tachycardia and permanent junctional re- thnt right atrial menn pressures stays normnl in many
entrant tachycardia. Severe bradycardia, typically from infants with congestive failure. Edema on the feet occurs
complete heart block, can also result in heart failure. late. Common to both left- and right-sided failure is the
With a normal heart, hemoglobin levels of 5 g/ dL can presence of cardiac enlargement, third sound gallop and
result in heart failure. In a diseased heart, failure may be poor peripheral pulses with or without cyanosis (Table 16.5).
precipitated even with hemoglobin levels of 7-8 g/ dL.
Treatment
Clinlcal Features
Management of heart failure is a four-pronged approach
The recognition of cardiac failure in older children is based for correction of inadequate cardiac output: (i) reducing
on the same principles as in adults. cardiac work, (ii) augmenting myocardial contractility, (iii)
improving cardiac performance, and (iv) correcting the
Symptoms
underlying cause. Identifying the cause is important since
Slow weight gain is related to two factors. The infant takes it has direct bearing on survival.
small feeds because of easy fatigability and there is an
excessive loss of calories from increased work of breathing. Reducing Cardiac Work (Fig. 16. l)
Uncommonly, there may be an unusual gain in weight The work of the heart is reduced by restricting patient
due to collection of water, manifesting as facial puffiness activities, sedatives, treatment of fever, anemia, obesity,
or rarely as edema on the feet. The difficulty in feeding and by vasodilators. Mechanical ventilation helps when
may manifest itself as 'poor feeder', a complaint that the heart failure is severe by eliminating the work of breathing.
baby does not take more than one to two ounces of milk Neonates with heart failure are nursed in an incubator
at a time or that he is hungry within a few minutes after an~ ha_n dled minimally. The baby is kept propped up at
taking a small feed. Since hunger persists, the infant is an mclme of about 30°. The pooling of edema fluid in the
rr:·,~-~-.-:-~~- -·--- Tabl.e 16.3: Time of onset of congestive.failure
Age Lesion
Birth-1 week Duct-dependent systemic circulation (hypoplastic left heart syndrome, critical aortic stenosis, severe
coarctation, arch interrupti?n)_;total anomalous pulmonary venous return (obstructed), congenital mitral
J
and tricuspid valve regurg1tat1on, neonatal Ebstein anomaly
: 1-4 weeks Patent ductus arteriosus (PD:6:) in p~eterms, ventricular septal defect (VSD) with coarctation, persistent
truncus arteriosus, transp~s1t1on with large VSD or PDA, severe coarctation, critical aortic stenosis,
congenital mitral or tricusp1d regurgitation, single ventricle physiology with unrestrictive pulmonary
blood flow
. 1-2 months Transposition with VSD or PDA, endocardial cushion defects, VSD, PDA, severe coarctation; total
anomalous pulmonar~ venous r~t~rn, anomalous left coronary artery from pulmonary artery, single
ventricle physiology with unrestrictive pulmonary flow
. ~-6 months VSD, PDA. endocardial_ cushion defect; anomalous left coronary artery from the pulmonary artery,
coarct~tion, single ventricle physiology with unrestrictive pulmonary blood flow
- 396 E1tont1a1 Pediatric•
~
Tabla 16.4: Symptoms of cardiac laffuro Anemia fmpows 5trc~~ mi the _heart b4>...cause oft_~
Poor weight gain
dccrca,ed oxy~en carrying capacity o~ b~, Anemia
r<:~ult~ In tachycardia and i,n a hyperkir...ffic c!rcuLa.tory
Difficulty In feeding &t11tc, Correction of anem1a deaeare:s card.ta< w0rk_
Breathes too fast; breathes bettor whon held against tho Typlc;illy, pa cked cell volum~ ~t 10-2!"1 mL/k~ ar~
shoulder rnquln::d to correct se_vere a~rma; a fimgle _d~ r;f
Persistent cough and wheezing (um~cmldc IV i~ nftl~n. giw:n pnor to the tr.an<>fu.s1on. Less
Irritability, excessive perspiration and restlessness common condition.~ cau5ing1;trc~ to the heartar€ repea~ed
pulmonary crnboli, thyrotn"Aico.sm and t'Jbesir;.
Pedal edema
Va1iod ila tor" counteract the OOJnp£'flSafi")ry mechanisms
, Table 16.5: Signs of congestive cardiac fallure In heart failure and improve cardi.ac output (Fig. 16.1).
Left-sided Failure of oit11er side Right-sided fal/uro Art(!riolar and venous vasoconstriction i.6 mediated
failure through catecholamines. Arteriolar constriction maintains
blood pn:11~ urc by increasing the sy5temk Yascufar
Tachypnea Cardiac enlargement Hepatomegaly rc11istancc, which increases the work of heart (Fig. 16.2).
Tachycardia Gallop rhythm ($3) Facial edema Vcnoconstriction results in decreased ven.ous capz.dtant:e
Cough Peripheral cyanosls Jugular venous and increased venous return, increasing the fiHing
engorgement prcs~ure~ of the ventricles to increase the cardiz.c output.
Wheezing Small volume pulse Since compensatory mechanis ms are inappropriately
Rales in chest Lack of weight gain Pedal edema excessive, vasodilators, by reducing the arteriolar a..-i-J
venous va soconstriction, reduce the ·Nork of heart
Nitrates arc used as preferential venodilators.
.!. Peripheral resistance ACE inhibitors (captopril, enalapril) are effectiYe for
.!. Venous return
treating heart failure in infants and children. Th.er.=.e agents
suppress rcnin-angiotensin-aldosterone system tl-.~eby
reducing vasoconstriction and salt and water retention.
t Cardiac output
By suppressing catecholamiru:s, they prevent arrh:.·tlullas
and other adverse effects on the myocardium. Tur: rnajor
side effect of ACE inhibitors is cough, .....-hich ca.11 be
Improved tissue 0 2
troublesome. Persistent cough may necessitate th~ u..;;e cf
angiotcnsin receptor blockers, such as losartan. Llitia1h·,
it is necessary to monitor the renal function: Urine a.':2...·:sfs,
blood levels of creatinine and electrolytes once a v;e-~k for
6 to 8 w~eks. The.se medications may cause first-<lose
Better work capacity hypotens1on; the first dose should be one-quarte: of the
calculated dose.
Fig. 16. l: By reducing the systemic vascular resistance and . Although beta-blockers might precipitate CCF, faey
decreasing the venous tone vasodilators provide better work 1mpr.ove symptoms especially in patients with dihted
capacity. LVEDP left ventricular end-diastolic pressure cardrnmyopathy, who continue to have tach..-c2.Idia.
Useful agents include metoprolol and carvediloL Tree !atter
dependent areas reduces the collection of fluid in lungs,
thus reducing the work of breathing. At a temperature of
36-37°C, the overall circulatory and metabolic needs are Congestive cardiac failure
minimal, thus reducing work of heart. Humidified oxygen
.!. co Vasoconstriction
to maintain a concentration of 40 to 50% improves
impaired oxygenation secondary to pulmonary
congestion. If the infant or the child is restless or dyspneic, Venous
sedation may be appropriate. Opiates (e.g. morphine) or
benzodiazepine (midazolam) are useful for sedation in
't Venous tone
selected circumstances to reduce anxiety and lower the
catecholamine secretion, thereby reducing physical
activity, respiratory and heart rates. t Venous return
Fever, anemia and infection increase the work of the
heart. In infants and small children, the presence of
Increased work of heart
superadded pulmonary infection is difficult to recognize.
Antibiotics are, therefore, sometimes administered Fig. 16.2: Low cardiac output (CO) results in vasocoostriCf;()(l.
empirically. In older children, antibiotics are used, only if Increasing systemic vascular resistance (SVRJ and venous tccie
evidence of infection is present. leading to Increase In the work of heart
j 397 .
is preferred since it has properties of beta-blockers with hepatic, renal and pulmonary insufficiency increase the
peripheral vasodilation; treatment is started at low dose sensitivity of the myocardium to digitalis. Digoxin is
and increased. depending on tolerability (0.08 to 0.4 mg/ beneficial for symptom relief and is advised in patients
Jcg/day, maximum ~.O mg/kg/day). Calcium channel with mild, moderately severe or severe congestive failure,
advers~ly affect ca~d1~c contractility blockers and should with or without sinus rhythm. Digoxin can be combined
be avoided unless indicated for systemic hypertension. with ACE inhibitors for synergistic effect.
In the a~ute car~ sett~g, sodium nitroprusside is used
as a vasodilator, since it acts on the venous and arterial Intravenous /notroplc Agents
systems. Phosphodiesterase inhibitors such as milrinone These agents belong to three groups: (i) catecholamine
and calcium ~ensi~izers (levosimendan), have become inotropes: dopamine, dobutamine and adrenaline, (ii)
popular especially in. postoperative period. These agents phosphodiesterase inhibitors: amrinone and milrinone
~a~e P?werful vasodilatory.and inotropic effects. Specific (combine inotropic effects with peripheral vasodilation,
indications for use of vasodilators include acute mitral or inodilators) and (iii) levosimendan, a calcium sensitizer
aortic regurgit~t~on, ventricular dysfunction resulting that is used in acute care settings as a potent inodilator with
from myocard1hs, an.omalous coronary artery from systemic and coronary vasodilatation. Unlike milrinone,
pulmonary artery and in the early postoperative setting. it does not increase risk of rhythm disturbances.
If blood pressure is low, dopamine should be used, as an
Augmenting Myocardial Contractllity intravenous infusion. At a dose of less than 5 µg/kg/ min,
Inotropic. agents like digoxin improve cardiac output by dopamine causes peripheral vasodilation and increases
augmenting myocardial contractility. It has a rapid onset myocardial contractility. Renal blood flow improves,
of action and is eliminated quickly. It is available for oral resulting in natriuresis; higher doses result in peripheral
and parenteral administration. Oral digoxin is available vasoconstriction. The dose of dobutamine is 2.5 to 15 µg I
as 0.25 mg tablets and as digoxin elixir (1 mL = 0.05 mg) kg/min; the dose should be increased gradually until the
(Table 16.6). Parenteral digoxin (0.5 mg/2 ml) is available; desired response is achieved. In patients with dilated
its dose is 70% of the oral dose. Infants tolerate digitalis cardiomyopathy, dobutamine is used as 24 hours infusion
well. In a hospitalized patient, full digitalization should once or twice a week and retains its effectiveness for varying
be sought to maximize benefit. Children are digitalized lengths of time. Milrinone is given in infusion 0.3-0.7 µg /
within a 24-hour period; 1h of the calculated digitalizing kg/min following a loading dose of 50 µg /kg. The dose
dose is given initially, followed by 1A in 6-8 hours and the of levosimendan is 6 to 12 µg/kg loading dose over
final 1A after another 6-8 hours. The maintenance dose is 10 minutes followed by 0.05 to 0.2 µg / kg/ min as infusion.
usually one-quarter of the digitalizing dose (Table 16.6).
Improving Cardiac Performance by
Before the third daily dose, an electrocardiogram is done
Reducing Venous Return (Preload)
to rule out digitalis toxicity. Toxicity can be controlled by
omitting the next one or two doses. The PR interval is a Diuretics reduce the blood volume, decrease venous
useful indicator; if it exceeds the initial interval by 50%, return <1nd ventricular filling. This tends to reduce the
digitalis toxicity is present. The upper limit of normal PR heart size. The larger the heart, the more the wall tension
interval in infants is 0.14 second. and the poorer is its performance. With reduction in heart
Digitalis is used with caution in the following sih1ations: size and volume, the myocardial function and the cardiac
(i) premature neonates; (ii) heart failure due to output improve. Diuretics reduce the total body sodium
myocarditis; and (iii) very cyanotic patients. Myocardial thereby, reducing blood pressure and peripheral vascular
damage, gross cardiomegaly, hypoxia, acidosis, and resistance. This helps in increasing the cardiac output and
reducing the work of the heart.
f:·-;:~ '· ·iabl"e 16.6: Dosage ot"digoxin aiicf diuretics ~~-_-,. Diuretics are the first line of management in congestive
- ·. . Digitalizing Maintenance failure. The action of oral furosemide starts within 20 min.
dose, mg/kg dose Furosemide should be u sed in combination with a
µglkg/day potassium sparing diuretic (triamterene, spironolactone,
D~goxln
amiloride). The combination prevents potassium and
magnesium and reduces the risk of arrhythmias.
Premature, neonates 0.04 0.01
0.02-0.025 Furosemide activates the renin-angiotensin-aldosterone
~ month to one year 0.08 axis, which is responsible for vasoconstriction and sodium
1to3 years 0.06 0.015- 0.02
0.017 and water retention. When furosemide is combined with •
Above 3 years
:Diuretics
0.04 ACE inhibitors, the combination suppresses the axis and I
is, therefore, synergistic.
Furosemide 1-3 mg/kg per day orally or Sodium restriction is recommended but difficult to
1 mg/kg per dose. IV implement in infants and young children. Low sodium
· Spironolactone 1 mg/kg orally every 12 hours diets should be used, only if the heart failure cannot be
- 398 I
controlled with digitalis, diuretics and ACE inhibitors. CONGENITAL HEART DISEASE
However, it is prudent to advise such patients to avoid 't l lle"rt disease (CHD) encompasses a br0 , ,,
Congen1 a " . . 1 . '•u
salt-rich foods such as chips and pickles. Since heart failure .
an d d 1verse rai ' 1 ge of conditions t lat manifest fro ... . ,.
increases calorie requirements, adequate intake is advised. 'od to late adulthood. In common terms Cl-ID
t 1
premap~1 '
tural heart defects that arc present at birth
Correcting the Underlying Couse ref ers to s tn lc · I · ·
Diagnosis requires a syste.mnt1c approac 1 mcluding
The focus of management of CHF has shifted towards . t y pl,ysical exammat1on, chest X-ray, ECG and
h is or , . . t'
identifying and correcting the underlying cause. It is now echocardiography. Palhat1~e or cor~ec 1ve surgery is
possible to rapidly identify the cause of CHF in most feasible for most patients with CHD, if undertaken in a
children with suspected heart disease. Many of these are timely fashion.
managed by curative or palliative operations. A diagnosis
of idiopathic dilated cardiomyopathy requires exclusion Epidemiology and Etiology
of conditions that are known to cause ventricular CHO accounts for nearly one-third of all major congenital
dysfunction. The conditions that might be missed are anomalies. The prevalence of CHD in infancy is estimated
sustained tachyarrhythmias, coarctation of aorta and at 6-8 per 1000 live births; 25% are l.ife-threat~ning and
obstructive aortitis, anomalous origin of the left coronary require early intervention. A prop~rtion ?f patients with
artery from pulmonary artery and hypocalcemia. It is CHD have an identifiable genetic basis (Table 16.7).
important to look for subtle evidence of sustained Table 16.8 shows the association of CHD with acquired
tachyarrhythmias. Anomalous origin of the left coronary disorders and teratogens.
artery is treated surgically.The presence of CCF in a child
with rheumatic heart disease does not necessarily mean Physiology of Congenital Heart Disease
presence of active carditis. In any patient of rheumatic Pressure, Flow and Resistances
heart disease, if active carditis has been excluded and an
adequate trial has been given to medical management, The pressures and resistances in the pulmonary and
operative treatment should be considered. Uncommon systemic circulations are indicated in Table 16.9. The
causes of CCF in infants include upper respiratory obstruc- pulmonary and systemic flows are equal, if there are no
tion, hypoglycemia, neonatal asphyxia and hypocalcemia. abnormal communications between the two sides.
-
Table 16.7: Inherited syndromes associated with congenital heart disease
Syndrome Genetic mutation; inheritance Cardiac lesions Other features
CATCH 22 Microdeletion in 22q; Interrupted aortic arch, TOF, Cleft palate, hypocalcemia,
autosomal dominant VSD, persistent truncus thymic hypoplasia, nasal
arteriosus, double outlet regurgitation, gastroesophageal
right ventricle reflux, learning disability
Williams-Beuren Microdeletion in elastin Supravalvar aortic stenosis, Elfin facies, mental retardation,
(7q11.23); AD pulmonary stenosis, hypersocial personality, short
hypertension stature, hypercalcemia
Down Trisomy 21; Robertsonian AV canal defect, perimemb- Characteristic facies, clinodactyly,
translocation or mosaicism ranous VSD, TOF mental retardation; hypotonia
Turner 45XO or 46/45XO mosaic Bicuspid aortic valve, Short stature, gonadal dysgenesis
coarctation lymphedema
Noonan PTPN11;AD Pulmonic stenosis, hypertro- Short stature, dysmorphic facies,
phic cardiomyopathy, ASD webbed neck, developmental
delay, cryptorchidism
VATER association Sporadic VSD, TOF Vertebral, renal and limb defects,
anal atresia, tracheoesophageal
fistula
Holt-Oram TBX5;AD Ostium secundum ASD; VSD Radial ray anomalies
CHARGE association CHD7; often de novo Branch pulmonary artery Coloboma, growth failure,
stenosis, TOF, VSD choanal atresia, genital
hypoplasia, ear anomalies
• Alagille JAG1; most cases are de novo Pulmonary stenosis, TOF Dysmorphic facies, cholestatic
jaundice, butterfly vertebrae,
renal anomalies
AD: Autosomal domina~t; AV: Atrioventricular; ASD: Atrial septal defect; TOF: Tetralogy of Fallot: VSD: Ventricular septal defect
j 399 .
Table 16.8: Pren t 1· · · -i
a a exposures that increase risk of Increase in pulmonary vascular resistance means
congenital heart disease , obstructive disease in the pulmonary circuit. The
Gestational diabetes (tr .. . · pulmonary vessels develop medial hypertrophy and later
fects hypoplasti ft anspositi~n, atnoventricular septal
de ' 1
c e heart, card1omyopathy, PDA) intimal changes are added, to further obstruct the flow of
blood through the pulmonary circulation. After a certain
Febrile illness in first trimester (increased risk)
stage, it is an irreversible process. The increase in
_Rubella (PDA, peripheral pulmonary stenosis, VSD) resistance to flow in the pulmonary circuit is associated
Lupus (complete heart block) with reduction in flow. The increase in pressure in the
Phenylketonuria (VSD, TOF, PDA, single ventricle)
pulmonary artery associated with normal resistance is
called h yperkinetic pulmonary arterial hypertension
Vitamin deficiency (increased risk of heart disease) whereas when the pressure is increased due to increase
Ter~togens (first t~ime~ter), e.g. anticonvu lsants, NSAIDs, in pulmonary vascular resistance, it is called obstructive
cotnmoxazole, thalldom1de, retinoic acid pulmonary arterial hypertension. Clinically, the two
Exd~ot~ure to organic solvents, herbicides, pesticides, ionizing conditions can be distinguished on clinical examination.
ra 1a ion
Fetal Circulation (Fig. 16.3)
NSA!Ds: Nonsteroidal anti-inflammatory drugs; PDA: Patent ductus
artenosus; TOF: Tetralogy of Fallot; VSD: Ventricular septa! defect The heart assumes its normal four-chambered shape by
the end of 6 weeks of intrauterine life. From then on only
· According to Poiseuille's equation modified for minor changes occur and consist mainly in the growth of
application to blood flow through vessel~, the heart as a whole with increasing age of the fetus. For
Pressure= Flow x Resistance the exchange of gases, the fetus is dependent on placental
circulation, whereas the neonate is dependent on the
The pressure is measured in mm Hg, flow in liters/ lungs. Immediately following birth, the lungs expand with
min and resistance in dynes/ sec/ ems or units (80 dynes/ air and the gas exchange function is transferred from the
sec/ems= 1 unit). Although this equation is not strictly placenta to the lungs; following variou s circulatory
accurate when applied to flow of blood in pulmonary and adjustments.
systemic circuits, it helps in understanding the hemo- Blood oxygenated in the placenta is returned by way
dynamics. of umbilical veins, which enter the fetus at the umbilicus
Systemic pressure = Systemic flow x peripheral vascular and join the portal vein (Fig. 16.3). The ductus venosus
resistance provides a low resistance bypass between the portal vein
Pulmonary arterial pressure = Pulmonary flow x pulmonary and the inferior vena cava. Most of the umbilical venous
vascular resistance blood shunts through the ductus venosus to the inferior
It is thus obvious that the pressure in a vessel is vena cava. Only a small proportion mixes with the portal
dependent on the flow through the vessel and the resistance, venous blood and passes through the liver. Blood from
offered by the vessel to the flow of blood. It is possible to inferior vena cava comprising that from hepatic veins,
increase the pressure in a vessel either by increasing the umbilical veins and tha t from lower extremities and
flow or by increasing the resistance. Increase in flow ki~neys enters the right atrium. On reaching the right
through the pulmonary artery means a left-to-right shunt, atnum, the bloodstream is divided into two by the inferior
as occurs in atrial or ventricular septa! defect or patent margin of septum secundum-the crista dividens. About
ductus arteriosus. Generally, this increase in flow is not one-third of the inferior vena cava blood enters the left
associated with significant increase in pressure as the atrium, through the foramen ovale, the rest two-thirds mix
distensibility characteristics of the pulmonary artery are with the venous return from the superior vena cava to
.such that it can accommodate almost three times the normal enter the right ventricle.
flow without an increase in pressure. Hence, large left-to- The blood reaching the left atrium from the right atrium
right shunts can take place without an increase in pressure. mixes with small amount of blood reaching the left atrium
r-...,.~!--'~'· -i'ai>ie· 16 . 9 ; · sy~tolic ~nd diastolic p.res~ure~·and resist~nce in th~ pulmonary and systemic .circuits
T..-.-~ __ ,, \
· ;· Chamber/v~ssel
t
At birth Adult
I 401
•
L _r·
SVC PV SVC PV
i
IVC I ' 10 10 PV Ive , 0--8 6-1 0
L PV
RA RA LA
60/10
25/0--8 120/0-10
RV LV RV LV
60/40 60/40 PA Ao
PA
I DA
Ao
25/10 120f75
Rg. 16.4: Pressure and resistance in the right- and left-sided chambers and vessels at birth compared to adults. Ao aorta; DA
ductus arterlosus; IVC Inferior vena cave; LA left atrium; LV left ventricle; PA pulmonary artery; PV pulmonary ve in; PVR periphera l
vascular resistance; RA right atrium; RV right ventricle; SVC superior vena cave
i. Pretricuspid versus post-tricuspid shunts of the prolonged right ventricular ejection time and
ii. VSD-PS physiology prolonged "hang-out" interval resulting from increased
iii. Single ventricle physiology capacitance of the pulmonary circulation. Pulmonary
iv. Duct-dependent lesions arterial hypertension (PAH) is typically absent or, at most,
v. Unfavorable streaming and parallel circulation mild. The presence of moderate or severe PAH in ASD is
worrisome and suggests the onset of irreversible changes
Pretrlcuspld versus Post-tr/cuspid Shunts in the pulmonary vasculature.
Acyanotic heart disease with left-to-right shunts is Post-tricuspid shunts are different in that there is direct
traditionally classified as pretricuspid and post-tricuspid transmission of pressure from the systemic to the
shunts. There are important differences in physiology that pulmonary circuit at the ventricular level (VSD) or great
impact clinical manifestations and natural history. Left- arteries (PDA and aortopulmonary window). The shunted
to-right shunts at or proximal to the level of the atria are blood passes through the lungs and finally leads to a
known as pretricuspid shunts. They include atrial septal diastolic volume overload of the left ventricle. The
defects and partial anomalous pulmonary venous hemodynamic consequences are dictated by the size of
connection. The left-to-right shunt and the consequent the defect. For patients with large post-tricuspid shunts,
excessive pulmonary blood flow is dictated by relative symptoms begin in early infancy, typically after regression
stiffness of the two ventricles. Since the right ventricle is of elevated pulmonary vascular resistance in the newborn
relatively stiff (non-compliant) at birth and during early period.
infancy, the shunt is small. Over the years, the pulmonary The excessive pulmonary blood flow returns to left
vasculature becomes capacious and right ventricle atrium and flows through the mitral valve resulting in
progressively enlarges to accommodate the excessive apical diastolic flow murmur that is a consistent marker
pulmonary blood flow. This explains why atrial septal of large post-tricuspid shunts. The left atrium and ventricle
defects (ASD) seldom manifest with symptoms of are dilated as a result of this extra volume. Elevated
pulmonary over-circulation durin~ infan~y and
childhood. The clinical signs are also easily explained by
the physiology of pretricuspid shunts. The ~iast~lic flow
tn.urmur of ASD is across the much larger tncusp1d valve
and is, therefore, relatively subtle or even inaudible. The
pulmonary artery pressure is an inevitable consequence
of large post-tricuspid shunts, and is labeled hyperkinetic
PAH. This needs to be distinguished from elevated
pulmonary vascular resistance that results from long-
standing exposure to increased pulmonary blood flow.
Ill
f
excessive blood in the right ventricle is ejected into the Correction of large post-tricuspid shunts results in rapid
Pulmonary artery resulting in an ejection systolic murmur. and dramatic reduction in elevated pulmonary artery
The second heart sound splits widely and is fixed because pressures.
-402
1
Essential Pediatrics
Table 16.10: Broad physiologic categories of The best example of VSD-PS physiology is ~etra~
congenital heart disease Fallot (TOF). In its le~st s.evere form, TOF _is ?ften not
Acyanotlc heart disease: Left-to-right shunts associated with cyanos1s (pmk TOF). Here ~Sis significant
Pretricuspid: Partial anomalous pulmonary venous drainage enough to result in a large pressure gradient across the
atrial septa! defect ' right ventricular outflow tract (RVOT), but not sever
Ventricular: Ventricular septal defects (VSD) enough to result in a reductio~ in pul~onary blood flow~
Great artery: Aortopulmonary window, patent ductus; ruptured Pink TOF is typically associated with a loud ejection
sinus of Valsalva systolic murmur because of a reasonab~e vol um~ of blood
Both pre- and post-tricuspid: Atrioventricular septal defect, left flowing across the RVOT. As the seventy of PS increases
ventricle to right atrial communications pulmonary blood flow declines and the intensity or
murmur declines progressively. Identical symptoms and
Acyanotlc heart disease: Obstructive lesions
physical findings are present in (i) complete transposition
Inflow: Cor-triatriatum, obstructive lesions of the mitral valve of great arteries with VSD and pulmonic stenosis,
Right ventricle: lnfundibularstenosis, pulmonary valve stenosis, (ii) double outlet right ventricle with pulmonic stenosis
branch pulmonary artery stenosis
and a large subaortic VSD, (iii) tricuspid atresia with
Left ventricle: Subaortic membrane, valvar aortic stenosis, diminished pulmonary blood flow, (iv) single ventricle
supravalvar aortic stenosis, coarctation of aorta
with pulmonic stenosis, and (v) corrected transposition
Misce~lane~us: Coronary artery abnormalities, congenital mitral of great arteries with VSD and pulmonic stenosis.
and tncusprd valve regurgitation
Cyanotlc heart disease Single Ventricle Physiology
Reduced pulmonary blood flow 1his refers to a group of conditions where there is complete
Intact interventricular septum: Pulmonary atresia with intact mixing of pulmonary and systemic venous returns. In
ventricular septum, critical pulmonic stenosis with right-to-left addition to single ventricle (double inlet ventricle), a
shunt at atrial level, Ebstein anomaly; isolated right ventricular variety of conditions come under the category of single
hypoplasia ventricular physiology. Atresia of one of the AV valves,
Unrestrictive ventricular communication: All conditions listed severe hypoplasia of one of the ventricles, severe
under VSD with pulmonic stenosis straddling of one of the AV valves over a large VSD are
Increased pulmonary blood flow all examples of situations where there is mixing of
Pretricuspid: Total anomalous pulmonary venous pulmonary and systemic venous returns. The clinical
communication, common atrium manifestations are dictated by whether or not there is PS.
Post-tricuspid: All single ventricle physiology lesions without In absence of PS, there is excessive pulmonary flow
pulmonic stenosis, persistent truncus arteriosus, transposition especially in infants because of the relativelv lower
of great vessels pulmonary vascular resistance. The propo; tion of
Pulmonary hypertension oxygenated blood from pulmonary veins that mixes with
the systemic venous return is high. Cyanosis is minimal
Pulmonary vascular obstructive disease (Eisenmenger
physiology) and measured oxygen saturation may be 90% or more.
However, preserved oxygenation is at the cost of heart
Miscellaneous fail_ure and permanent elevation of pulmonary vascular
Pulmonary arteriovenous malformation, anomalous drainage resistance (pulmonary vascular obstructive disease). If the
of systemic.veins to LA child survives infancy, pulmonary vascular resistance
progressively increases with increasing cyanosis.
VSD-PS Physiology {Fa/lot Physiology] Single ventricle and its variants can be associated with
This situation is characterized by a large communication varying degrees of PS. The features are similar to VSD-PS
at the ventricular level together with varying degrees of physiology except for relatively severe hypoxia because
obstruction to pulmonary blood flow. Typically, this is in of free mixing of systemic and pulmonary venous return.
the form of subvalvar (infundibular), valvar, annular Palliative operations are the only option for most
(small annulus) and occasionallysupravalvarstenosis. The conditions. The definitive procedure is the Fontan
free communication between the two ventricles results in operation that allows separation of systemic venous rehll11
equalization of pressures. Severity of PS dictates the from pulmonary venous return thereby, eliminating
volume of blood flowing through pulmonary arteries and, cyanosis.
d pendent on an open PDA (duct-dependent systemic Difficult Feeding and Poor Growth
·erculation, DDSC) or pulmonary blood flow is duct The parent may report that the child has difficulty feeding.
~ependent (duct-dependent pulmonary c~rculatior_i, This is usually a feature of an infant with congestive heart
DDPC). Closure of the PDA in DDSC results m systemic failure and may include slow feeding, small volumes
hypoperfusion (often mistaken as neonatal s~psis), as i_n consumed during each feed, tiring easily following feeds
hypoplastic left heart syndrome, where the entire systemic and requirement of periods of rest dur~g fe~ds. Excessive
circulation is supported by the right ventricle through the sweating involving forehead or occ1put i~ co~~only
PDA, and interrupted aortic arch where the descending associated. Not infrequently, no history of feeding difficulty
aortic flow is entirely through the PDA. Severe coarctation may be obtained, but examination of growth charts reve_a ls
and critical aortic stenosis are also examples of DDSC. that the growth is not appropriate for age. A recen~ decline
Closure of PDA in DDPC results in severe hypoxia and in growth rate (falling off the grow~ curve) or weight that
cyanosis in neonates; examples include all forms of is inappropriate for age (<5th cenhle) i:nay result from a
pulmonary atresia (irrespective of underlying heart defect) large left-to-right shunt. Character~shcally, growth
where the PDA is the predominant source of pulmonary retardation affects weight more than height.
blood flow . Patients with pulmonary atresia, where
pulmonary blood supply is from major aortopulmonary Difflcult Breathing
collaterals, may survive even after the PDA closes. Critical
Tachypnea (respiratory rate >60/ min. in infants <2 mon_ths;
PS can present as duct-dependent pulmonary blood flow . >50/min in older infants; >40 / mm after 1 year) is a
Newborns with severe Ebstein anomaly can also present manifestation of heart failure in newborns. For infants,
as DDPC (physiologic pulmonary atresia) even though subcostal or intercostal retractions together with flaring
the pulmonary valve is anatomically normal, because of of nostrils are frequently associated with tachypnea.
inability of the right ventricle to function effectively.
. Neonates with duct-dependent physiology require Frequent Respiratory Infections
prostaglandin El (PGEl) for survival. Early recognition
The association of respiratory infections that are frequent,
of a duct-dependent situation allows early initiation of
severe and difficult to treat with large left-to-right shunts
PGEl and stabilization until definitive procedure is
is frequent but not a specific feahire.
accomplished.
Unfavorable Streaming and Parallel Circulation Specific Syndromes
The p resence of chromo somal a n om a lies or other
Unfavorable streaming refers to a situation where oxygen
rich pulmonary blood flow is directed towards the syndromes that are associated with CHD should alert the
pulmonary valve and poorly oxygenated blood towards clinician to the presence of sp ecific ca rdiac defe cts.
the aortic valve. The bes t example of unfavorable Trisomy 21 is the commonest anomaly associated with
streaming the parallel circulation in transposition of great heart disease; others include trisomy 13 and 18, Turner
arteries (TGA) with intact ventricular septum. Here and Noonan syndromes, and v elocardio faci a l and
survival depends on the presence of a communication DiGeorge syndromes (Table 16.7).
(ideally at atrial level) that allows mixing of pulmonary Nadas Criteria
and systemic venous return. The presence of a VSD may
improve the situation in TGA but significant cyanosis is The assessment for presence of heart disease can be done
usually present unless the pulmonary blood flow is using the Nadas criteria. Presence of one m ajor or h vo
torrential. minor criteria is essential for indicating the presence of
heart disease (Table 16.11).
Clinical Features
Major criteria
While it is often easy to recognize the presence of CHD in Systolic murmur grade Ill or more in i11te11sity: A pansystolic
older children, manifestations of heart disease can often murmur is always abnormal no matter what is its intensity.
be subtle in newborns and young infants. Conditions that
do not primarily involve the cardiovascular sy~tem can
result in clinical manifestations that overlap with those Table 16.11: Nadas' criteria for clinical diagnosis of
resulting from CHD in the newborn. Nonetheless, careful congenital heart disease
clinical eva lua tion is often r ewarding and a llows Major Minor
identification of CHD in most infants and many newborns.
Cyonos/s
Parents seldom report cyanosis unless it is relatively severe
(saturation <80%). It is often easier for them to notice
Systolic murmur grade Ill
or more
Diastolic murmur
Cyanosis
Systolic murmur grade I or II
Abnormal second sound
Abnormal electrocardiogram
Abnormal X-ray
I
Congestive cardiac failure Abnormal blood pressure
episodic cyanosis (when the child cries or exerts).
- 404 1
There are only three lesions that produce a pansystolic Abnormal electrocardiogram: Elec~ocar.diogram is used to
murmur: VSD, mitral regurgitation and tricuspid determine the mean QRS axis, r.1ght or left atrial
regurgitation. An ejection systolic murmur may be due to hypertrophy and right or left ventricular hypertrophy.
an organic cause or it may be functional. An ejection Criteria for ventricular hypertrophy, based only on voltage
systolic murmur associated with a thrill is an organic criteria are not diagnostic for the presen~e of heart disease,
murmur. Grade Ill ejection systolic murmur of a functional since these may be affected by changes m blood viscosity,
type may be heard in anemia or high fever especially in electrolyte imbalance, position of electrodes and thickness
small children. of the chest wall.
A 1111111ber of c11ildre11 aro1111d the age of 5 years may have a Abnormal X-ray: The reason for abnormal X-ray.as a minor
soft, slwrt ejection systolic murmur. If it is accompanied with criterion is twofold. In infants and smaller children, the
a normal second sound, then it is unlikely to be significant. heart size varies with expiration and inspiration. If there
Before labeling a murmur as innocent, it is necessary to is cardiomegaly on an inspiratory film, it suggests heart
reassess after an interval. Typically, innocent murmurs disease. The second reason is that enlarged thymus in
are often detected during a febrile illness and often children up to 2-year-old might mimic cardiomegaly.
disappear. It may be necessary to obtain an ECG and an Fluoroscopy is helpful in separating the shadow of the
echocardiogram to rule out heart disease and allay
thymus from the heart.
parental anxiety.
Abnormal blood pressure: It is difficult to obtain accurate
Diastolic murmur: A diastolic murmur almost always blood pressure in smaller children. It is important to use
indicates the presence of organic heart disease. appropriate sized cuffs while measuring blood pressure.
Central cyanosis: Central cyanosis suggests that either
unoxygenated blood is entering the systemic circulation Diagnostic /mpllcatlons of the Second Heart Sound
through a right-to-left shunt or blood passing through the Of the various heart sounds and murmurs, the most
lungs is not getting fully oxygenated. Oxygen saturation important is the assessment of the second heart sound
of the arterial blood is less than normal (normal being (Fig. 16.5). The normal second heart sound can be
around 98%). If blood is not getting oxygenated in the described in three parts:
lungs, it is called pulmonary venous desaturation and i. It has two components: Aortic closure sound (A2) and
indicates severe lung disease. Cyanosis due to a right-to- pulmonary closure sound (P2).
left shunt indicates presence of heart disease. Central
cyanosis is present in fingers, toes and mucous membranes
Second Heart Sound
(mouth, tongue). It results in polycythemia and clubbing.
Peripheral cyanosis does not imply the presence of heart Splitting Expiration Inspiration
disease. Peripheral cyanosis results due to increased oxygen
extraction from the blood by the tissues, and is seen in fingers
and toes but not in mucous membranes. The arterial oxygen
Normal
D
saturation is normal. Presence of central cyanosis indicates
CHD if lung disease has been excluded. However, cyanosis
that is obvious clinically usually results from significant
V\lide and variable
D
•
desaturation (typically <85%). Poor lighting, anemia and V\lide and fixed
dark skin may mask cyanosis. The routine use of pulse
oximeters allows detection of mild hypoxia. Saturations
<95% while breathing room air are abnormal.
Congestive cardiac failure: Presence of congestive cardiac
Paradoxical
D
failure indicates heart disease except in neonates and
infants, where it might occur due to extracardiac causes, Single second sound
fl
including anemia hypocalcemia and hypoglycemia.
I
Minor criteria
Systolic murm11r less than grade III: However, soft, less than
grade Ill, murmurs by themselves do not exclude heart
I disease.
Abnormal second sound: Abnormalities of the second sound
always indicate presence of heart disease. It has .bee.n
included as a minor criterion only because auscultation is
Fig. 16.5: Second sound (S2): The relationship of aortic !A l
and pulmonlc component (P2) In Inspiration and explrati~
Single S2 means that It may be either A2 or P2 or a combinati
2
--
Disorders of Cnrdlovnaculnr sy1torn I 40tJ -
ii. During quiet breathing, both the componl•nls nrc h1 wldu 111 uxplrnllo11 hut 111u·wwu durl11p, Jnt1plrnllrn1
superimposed on each other d.ming cxpil'nllon, thus (Fig. I(J,r,), A ul11p,lu 11L1C01HI 11rn111d 11w111111 tlrnl It 111 c•lflwr
only a single second sound is henrd.. During lnsplm- A2 m 1'2 01· 11 \:Olll h In11 IInn. 'J'l w de •c:h1I"' 1 wl 1d lwr It lri um tic
tion, the aortic component comes eal'ly whcrem; lhe or pu I1111111 le 01· n n1111hl 1111111111, clc•pt•f u 111 11011111 Iht• lrn:.1 llon
pulmonary component is ddayed, resulting inn :;pill 01' lllll'llfllly o( llH' Hl11gh• 11t•rond 11111111d 1 '1111 llll flll! fllHkaf
in which the A2 precedes the P2. prnfllt'. 111 ll•ll'lllogy o( l111llot.11nly ,1 11l11y,ll• ~12 11 lw;mJ aHd
iii. The aortic component is louder thnn the pulmonnl'y ll 11-l lhc /\21-1lrwe llw p11l111crr1k rnn1pww11t l11 d1·lay1•d and
component, except in young infants. Ho Hofl l11nt 11 IH l111111cllbh:. l11 VSI J wltlt p11lr111111ary arlNial
When we say that the second sound is normal, it Is in hypcrtemd1111 uncl rl>)hl -lo· ldl 1~1111111 (Hl111~11nwng11 r
context of the above three aspects. Abnormalities of lhe ro111pll'x), 1-1 l11gle S2 rcpf'l'Mc11l1111 m111hl1111tl1m of A2 rurcJ
second sound might occur in each of these aspects. 1'2. Whlll• bmwd 011111wcultnllo1111lo11c, ll mly.llt lw difficult
to dlffcrc111'1ntc l>clwec11 ll'lrnlogy of Jl11llot and
Abnormalities of aortic compo11e11t: The A2 mny be Else11me11ger complex, the '11 Nlory a11d diu11t X-ray can
accentuated or diminished in intensity. lt can nlso occm
distinguish these cond lllonH.
early or late in timing. The A2 is accentuated in systemic
hypertension from any cause and in AR; diminished or Imaging Studies
maybe absent when the aortic valve is inunobile because
of fibrosis or calcification; or if absent, in aortic valve Eclioctmliogrn11/1y: Echocaruiogrnphy h;w n·v'1l11tioniz ·d
atresia. The A2 is delayed when the left ventricular ejection the dingnosis or Cl ID ;mu it1:1 diagrumtk yi1·IJ mtlk ... this
inves tigation cos t-cffoclive (Pig. H>.6). Thb1 iHparticularly
is prolonged as in aortic valvar or subvalvar stenosis,
patent ductus arteriosus with a large left to right shunt, true ror infonti; i111d newborns Whew CX<.:<-•llcnl imay,cs arc
readily obtained. 'franscsoplrngcill cchocardiography can
AR, left bundle branch block and left ventricular failure.
supplement transthoracic studies in older children.
The A2 occurs early in V5D, mitral regurgitation and
constrictive pericarditis. Cardine magnetic resonance imaxinx: Cardiac MRI is
important for evaluation or Cl ID, C8pcciillly in older
Abnonnalities of pulmouic component: The P2 may be patients and for postopcrnlive evaluation . Mf<f also
accentuated or diminished in intensity or delayed in defines cxtrarnrdiac structures such as brnnch pulmonary
timing. Although it may occur early in tricuspid arteries, pulmonary veins anti norlopulrnonnry colla terals.
regurgitation, it is not recognized since tricuspid Useful physiologic dllta (blood flow calc ul ations at a
regurgitation as an isolated lesion (without pulmonary number of locations; estimate of ventricular function) is
arterial hypertension) is rare. Accentuated P2 is present obtained. Limitations inclutlc lack of expe rti se for
in pulmonary arterial hypertension from any cause. The interpretation and need for gcncrnl anesthesia to enable
P2 is diminished in intensity in pulmonic stenosis. It is breath-holding.
absent when the pulmonary valve is absent as in
pulmonary valvar atresia. The P2 is delayed in pulmonic Computecl tomograpl,1y: CT overcomes some of the
stenosis, atrial septal defect, right bundle branch block, limitations of MRI because it has a much lower image
total anomalous pulmonary venous connection and type acquisition time. However, exposure to ionizing radiation
A WPW syndrome. is a concern.
Abnormalities in splitting of t11e sec01id sound (52): The Diagnostic clmliac cat11cterizatio11: The role of diagnostic
normal 52 is single (or closely split, <0.03 sec) in expiration cardiac catheterization for patients with CHD has d eclined
and split in inspiration with the louder A2 preceding P2. with the availability of high quality cchocardiography,
Wide splitting of the second sound is defined as splitting MRI and CT. Since cardiac cathclcrization is an invasive
during expiration due to an early A2 or late P2 or the A2- procedure, its performance requires plnnning so that the
P2 interval of 0.03 sec or more during expiration. If the information desired may be obtained with minimum risk
interval increases during inspiration, it is called wide to the patient. Diagnostic cardiac cathctcrization should
variable splitting, but if it is the same in expiration and be advised, if non-invasive investigations do not provide
inspiration it is defined as widely split and fixed 52. Wide information that is required for surgery.
and variable splitting of 52 is seen in pulmonic st~n~si~,
I
Definitive and Palllatlve Treatment
mitral regurgitation and V5D. In pulmonic stenosis, It IS
due to a delay in P2 whereas in mitral regurgitat.io~ and To ensure the best possible resu Its of management of CHD,
VSD, it is due to an early A2. Wide and fixed sphttmg of it is necessary to have a team of qualified individuals who
the S2 occurs in atrial septal defect, right bundle branch are part of a comprehensive pediatric heart program.
block and total anomalous pulmonary venous connection
and is due to a delay in P2. Surgery
The delay in A2 results in closely split, single or Surgery is still the best option for definitive treatment or
Paradoxically split 52. In paradoxically split 52, the split palliation of most CHO. Surgeries for CHD are broadly
·-
- 40s 1 Essentlol Pediatrics
Basal
,,.- .
"!:"~~~
Apical
Fig. 16.6: Two-dimensional echocardlography. An Illustrative example of how the ventricular septum can be sectioned at different
levels to screen for ventricular septal defects. The lines with arrows represent levels at which cross-sectional Images are obtained.
The still frames of the respective echocardiograms are shown In relation to each of the level at which a section Is obtained . Ao
aorta; LV left ventricle; PA pulmonary artery; RV right ventricle; RVOT right ventricular outflow tract
classified as open heart (requiring use of cardiopulmonary ventricle continues to support the systemic circul <:1 tion,
bypass-CPB) and closed heart (not requiring CPB). Most TOF repair where the pulmonary valve is rendered
corrective operations and many palliative operations fall incompetent through a trnnsi"lnnular patch nnd oper;:itions
under the former category. These procedures are generally that require the placement of a right ve ntri cle to
a more significant and expensive undertaking because of pulmonary artery conduit. Com.•clive surgeries associated
the use of the CPB circuit. The morbidity of open heart with excellent long-term survival include the arterial
operations is proportionate to the duration of exposure to switch operntion, repair of total anomalous pulmonary
CPB and the cross-damp time (the period of time when venous connection nnd conrctation.
heart beating is deliberately brought to a standstill through
the use of cardioplegia). Surgery for siugl<• veutric/c pl1ysivlogy: This ca tegory
includes all anatomic examples of single ventricle. In
Corrective operations: Corrective surgery is possible for addition, this includes situations when one <1trio·
atrial and ventricular septa! defects, with no significant ventriculnr valve is ntrctic or one of the ven tricll's is
r-·
l .. Table 16.12: Congenital heart defects amenable to catheter-based interventions
lesion Procedure Comments
Atrial septa! defect Device closure Amenable to device closure, if the defect is in the fossa ovalis and has
sufficient margins
Patent ductus arteriosus Coil or device closure Majority can be closed by catheter interventions, except large
(PDA) PDA in infants
Muscular ventricular septa! Device closure Device closure is an option for older infants (>8 kg)
defect (VSD)
Membranous VSD Device closure Controversial; carries a small risk of heart block
Pulmonary valve stenosis Balloon pulmonary Treatment of choice for most forms except dysplastic valves in
valvotomy Noonan syndrome
Aortic valve stenosis Balloon aortic valvotomy Initial treatment of choice at all ages; however, dilated aortic valves
eventually need surgery
Branch pulmonary artery Balloon dilation with Stenting preferred to surgery
stenosis stenting
Coarctation of aorta Balloon dilation with Neonates: Surgery preferred due to high risk of recurrence
or without stenting Older infants: Balloon dilatation satisfactory
Children > 10 years: Dilatation with stenting is curative
Coronary artery fistula Coil or device closure Treatment of choice
Pulmonary arteriovenous Coil or device closure Treatment of choice when discrete; surgery preferred for diffuse
malformations malformations
. Duct-dependent pulmonary Stenting of the PDA Offered, in selected cases, as an alternative to Blalock-Taussig shunt
. circulation
. Pulmonary atresia with intact Valve perforation followed Preferred procedure in some centers
ventricular septum by balloon dilation
Ruptured sinus of Valsalva Device closure Preferred option in selected cases
aneurysm
. -
· Transposition of great arteries Balloon atrial septostomy · For palliation before definitive surgery
..
111111 408 I ~--------~~~----------~E~s=s~en~t~lo~l~Po~d~ln~t~rlc~1~--------------~~~~~---~
-
Patients "ith CHO show h~h pre\'1.tlen~ of malnutrition, Tnchypncn I!! prominent feature without, ~lg.niflc~l'lt
which impron~s :.ift~.r '-.'\.U~'Ction of th~ underlying gubco~tnl rcceflslon. Cynnosls cleepen~ a~ the '4Pf·ll
ex: ndition. progresses. Later gnflplng respiration and ap~ea t;isue~,
which tcnd1' to limpness and ultimately ano")(1~ ~(.1zur~,
:\fyoc..:nli.-1 dysf.1tt1.:tfon: Chronic Yolume overlond Spclhi cnn last from minutes to hours. Au~ltat1on .n:.-v:a1~
results in nmtricul.u ~nbr~"'nwnt and Yentriculnr softening or cllsnppcarancc of pu~mo~a~y C:J(;Ct1on
d\"'Sfunct:iun thlt is reY~~-J .1tter CQm.....:tion. A proportion murmur. The 1nnnagcmcnt is summarized m fable 16.13.
of patients ,,;th ~'-e~ hy1'oxia m,1y 1.fowlop severe
dysfunctiun in,·oh·in~ ~)th nmtrides. Heart failure is Natural History
mosth- the result of h~mudvn~uuic c"1nsequences of Some Cl-ID hnve n tendency towards spontaneous d<J!lu-rt
ini::re~~ pulmonary blQQ\.i tlo~,-. mitral or tricuspid valve nnd this influences the timing of intervc.'lltfon. Defee~
regurgitation and~\-ere myL1':.udi.1l h~~rtrophy. Systolic known to close spontnncously are atrial and ventricular
dysfunction is a relatin~ly le;.s rotnmon cause. septal defects, nnd patent ductus arteriosus. V~riablcs
Neurologic can..'t:.lucnc~ .111.i dt.1.·do11mn1t1frliiy: Chronic influencing the likelihood of spontaneous closure tnclud~
hypoxia, iu 11tcro hy'P'-1:\iJ. ..md h~-popt-rfusion and open- Age at cvnluation (lower likelihood of closure with
heart slllb--ery contribure suhst.mtially to morbidity. Brain increasing nge), size of the defect (smaller defects mort:
abscess is uniqucly a...'SDciared. with cyanotic heart disease
Table 16.13: Management of hypercyanotic spells
(typically beyond the a~ of~ ye.U'S).
Immediate steps
Eryt1rrocytosis: Older children with cyanotic CHO are Check airway; deliver oxygen by face mask or nasal cannula
prone to complications from chronically elevated red cell
Knee chest position
turnover. These include symptoms of hyperviscosity,
Sedate with morphine (0.2 mg/kg SC or ketamine 3-5 mg/kg/
gout, renal failure and gallstones.
dose IM)
Rlrytlrm disorders mrd sudden dcatli: Chronic enlarge- Sodium bicarbonate at 1-2 mlJkg (diluted 1:1 or in 10 ml.lkg
ment of heart chambers predispose to tachyarrhythm.ia. N/5 in 5% dextrose)
Ouonic right atrial enlargement (ASD, Ebstein syndrome, Correct hypovolemia (10 mlJkg of dextrose normal saline)
severe tricuspid regurgitation) p~sposes to atrial flutter. Transfuse packed red cell, if anemic (hemoglobin <12 g/dl)
Chronic right ,-entricular enlargement predisposes to Metoprolol at 0.1 mg/kg IV slowly over 5 min; repeat ever/
ventricular tachycardia and may precipitate sudden 5 min; for maximum 3 doses; may be followed by infusion at
cardiac arrest. This is a significant long-term concern after 1-2 µg/kg/min
TOF repair where the pulmonary valve is rendered Monitor saturation, heart rates and blood pressure; keep hE:art
incompetent. Left Yentricula r h ype rtrophy and rate below 100/minute
dysfunction is also associated. with high risk of ventricular
Persistent desaturation and no significant Improvement
tachycardia.
Consider vasopressor infusion: Methoxamine 0.1-0.2 mg. ~ri
Cyanotic spells: Patients with the VSD-PS physiology are dose IV or 0.1- 0.4 mg/kg/dose IM, or phenylephrine 5 p0 kg
prone to cyanotic spells. Cyanotic spells occur due to acute as IV bolus and 1-4 µg/kg/min as infusion
decrease in pulmonary blood flow, increased right-to-left If spells persist: Paralyze the patient, electively intubat& and
shunt and systemic desaturation due to (i) infundibular ventilate; plan for palliative or corrective surgery
spasm secondary to increase in circulating catecholamines, Seizures are managed with diazepam at 0.2 mg/kg t'.' or
during feeding or crying; or (ii) activation of mechano- midazolam at 0.1-0.2 mg/kg/dose IV
receptors in right ventricle (due to decrease in systemic Following a spell
venous return) or in left ventricle (due to reduced
Conduct a careful neurological examination; CNS imagi~g . if
pulmonary blood flow). These changes result in peripheral focal deficits are present
vasodilatation and fall in systemic vascular resistance,
Initiate therapy with beta-blocker at the maximally tola ~ated
producing increased right-to-left shunt and systemic
dose (propranolol 0.5-1.5 mg/kg q 6-8 hr); helps improve
desaturation.
resting saturation and decreases frequency of spells
A cyanotic sp ell is an emergency, which requires Ensure detailed echocardiography for disease morphology
prompt recognition and intervention to prevent disabling
Plan early corrective or palliative surgery
cerebrovascular insults or d eath. The spell needs to be
Administer iron in therapeutic (if anemic) or prophylactic dose
taken seriously also because it indicates the need for early
operation. It is commonly seen below 2 years (peaks 1Prevention
between 2 and 6 months). The onset is spontaneous and Counsel parents regarding the possibility of recurrence of spells
unpredictable and occurs more often in early morning, and precipitating factors (dehydration, fever, pain)
although it can occur at anytime in the day. The infant Encourage early surgical repair
cries incessantly, and is irritable and inconsolable.
Disorders of Cardiovascular System 1409 -
\ikcly to dose) and location of defects (fossa ovalis ASD Detection of serious defects through fetal echocardio-
nnd perimembranous and muscular VSDs often dose) graphy enables delivery at a center with a pediatric heart
(Table 16.14). program. While echocardiography is recommended for
Without correction, many children especially those with future pregnancies after diagnosis of serious CHD in a
cyanotic CHO, will not sun i\ e beyond early childhood. child, this has low yield because only 2-8% CHO recur,
The outcomes are improved by correction through surgery with the highest risk for obstructive lesions of the left heart.
and, in some situations, through caU1eter interventions.
Ot?spite curative surgery, some patients have important ACYANOTIC CONGENITAL HEART DEFECTS
long-tem1 sequelae. For example, patients with tetralogy Atrial Septa! Defect
of Fallot who have undergone "curative" repair might
show progressive right ventricular dilation with increased Atrial septal defect (ASD) as an isolated anomaly accounts
risk of late heart failure and sudden cardiac death. There for 5-10% of all CHO. Based on anatomy, ASD is classified
are concerns after the arterial switch operation (aortic root as follmvs (Fig. 16.7):
dilation, silent coronary occlusion), AV canal repair (AV Fossa oval is ASD: They are located in the central portion
valve regurgitation) and coarctation (residual of atrial septum, in the position of foramen ovale. These
hypertension, aortic aneurysm). Operations that involve defects are amenable to closure in the catheterization
placement of conduits (pulmonary atresia, Rastelli laboratory.
operations) require replacement upon growth of the child.
Conditions associated with satisfactory long-term survival Sinus ve11os11s ASD: These are located at junction of
include small left-to-right shunts and bicuspid aortic superior vena cava and right atrium. These defects do not
valves. Survival is satisfactory for many patients with have a superior margin because the superior vena cava
atrial septal defect, coarctation of aorta, pink TOF, straddles the defect. These defects are associated with
mild Ebstein anomaly and some forms of corrected an?malous drainage of one or more right pulmonary
transposition of great arteries. veins.
Prevention of CHO Ostium pri11111111 ASD: These defects are created by failure
of septum primum, and are in lower part of the atrial
Most CHO do not have an identifiable etiology and there
is no effective strategy for their prevention. Education of
public on the risks associated with consanguinity, drugs
and teratogens in the first trimester of pregnancy and
widespread immunization against rubella h ave limited
Fossa ovalis A
role in preventing CHO. Fetal echocardiography is an
important modality for early diagnosis of CHO.
Conditions that involve major chamber discrepancy (such
as hypoplastic left heart syndrome), single ventricle and
common AV canal can be identified by routine four
ch~mber view screening as early as 14-16 weeks gestation.
With some refinement, additional conditions such as
tetralogy of Fallot, large VSD, transposition of great vessels
and persistent truncus arteriosus can be detected. Once a
serious CHO is identified, it is vital to counsel the families
abo~t postnatal manifestations, natural history, surgical Inferior vena cava Coronary sinus orifice
Options and their long-term outlook. Before 20 weeks of Fig. 16.7: Right-sided cardiac chambers showing the three
gestation, medical termination of pregnancy is an option. commonest types of atrial septa! defects (ASD)
septum; inferior margin of ASD ls formed by the
atrioventricular valve.
Cor01tan1 si11us ASD: An unroofod coronary sinus is a rare
communication between the coronary sinus and the left
atrium, which produces features similar to other types of
ASD.
Sounds
81 : Accentuated-loud T1
82 : Wide fixed split, P2++
X : Inconstant (infrequent)
RV LV
Murmurs +u ,U.
Shunt murmur: Absent PA Ao
Flow murmurs (a) Trlcuspid-delayed diastolic
(b) Pulmonary-ejection systolic
2
If ~'
DOM
Phono I
51
• rtr
A2P
I ,,.,.
ESM
I j•
Yentricular enlargement, prominent main pulmonary Rg. 16.12: EchoccJC~og;c c~ ASD. SL.~'CCC.OC S::Ci"i c:cs '.'f?!'o'I
arteI) segment, a relatively small aortic shadow and of the atrial septum shO\•.s ce e-~i ;:::os·e--.c: -.!eret --n ft.. ._w}.
plethoric lung fields. The left atrium does not enlarge in LA Jett atrium; RA righr amum: S\'C supe:-a -ere c~.~
size in atrial septal defect, unless associated \v;th other
anomalies like mitral regurgitation. Echocardiogram
shows increased size of the right Yentricle ,,;th paradoxical Ventricular Septa! Defect (VSDJ
Yentricular septal motion. 20 echo in subcostal ,;ew often This is the most common congenital cardiac lesion
best identifies the defect. The echocardiogram allows identified at birth accounting for one-quarter oi all Qfl)_
decision regarding suitability of catheter closure, based VSD is a communication between the two ,-entricles; 90':o
on measurements of the defect and the adequacy of are located in the membranous part of the \·entricu.. .lI
margins (Fig. 16.12). septum \dth ,·ariable extension into the rntL"'-..-IDar sctitum.
Others are located in the muscular septum and c.an t-e
Assessment of the Severity multiple (Fig. 16.13).
The size of the left-to-right shunt is directly proportional Hemodynomics
to the intensity of the murmurs and heart size. The larger
the shunt, the more the cardiomegaly and the louder the VSD results in shunting of oxygenated blood from foe left
pulmonary and tricuspid murmurs. to the right ventricle. The left ,·entricle st:irts contracting
before the right ventricle. The flow of blood from the lert-
Natural History and Complications to-right ventricle starts early in s~·stolt>. \\'hen the defect
is restrictive, a high pres-ure grddient is m.:iint.1ined
Heart failure is exceptional in infancy. A small proportion ber,.leen the two ventricles throughout the sy~tole. The
of patients might develop pulmonary hypertension by the murmur starts early, masking the first sound and
second or third decade. Closure of ASD is recommended continues throughout the systole with .1lm st the same
to prevent complications of atrial arrhythmias and heart intensity appe.uing as a pansystolic murmur on
failure in late adulthood. auscultation .rnd palpable as (\ thrill. T1.)w,ud the end of
m
systole, the declining left ventriC\ll.lr pressure becomes
Treatment lower th,m the aortic pressurt>. This results in closure of
Most fossa ovalis defects with good margins can be clos.ed the aortic va lve and occurri'nce of A2. At this time,
percutaneously in the catheterization laboratory with however, the left \"entricubr pre::.sure is still higher than
?<=elusive devices. Others require surgical closure. Closure the right vt.'ntricular pres. ure and the left-to-right shunt I
15 recommended before school entry to prevent late continues. The pansystolic murmur, therdore, ends
complications. Small defects (<8 mm) can be observed. beyond A2 completely masking it (Fig. 16.14).
Spontaneous closure is well recognized in small defects The left-to-right ventricular !'hunt occurs during systole
-that are diagnosed in infancy or early childhood. at a time when the right ventricle is also contracting and
II 412 1~--~----~-------=:::!!!!!~~~--~----~~~----~
Essontlol Podiatries
r
left-to-right shunt. There is also an increase in the intensity
of the P2.
Ventricular Septa\ Defect l .__--.-_,,Ji~ Cllnlcol Features
Sounds Patients with VSD can become symptomatic around 6 to
51 : Masked by murmur 10 weeks of age with congestive cardiac failure . Premahire
52 : Masked by murmur at LLSB: __. RA LA babies with a YSD can become symptomatic even earlier.
at second US widely split
J~ l~i
bu\ mobile Palpitation, dyspnea on exertion and frequent chest
53 : With small L--+R shunts infection arc the main symptoms in older children. The
RVl!l~H
precordium is hyperkinetic with a systolic thrill at the left
sternal border. The heart size is moderately enlarged with
a left ventricular type of apex. The first and the second
Murmurs sounds are masked by a pansystolic murmur at the left
Shunt murmur : Pansystollc PA Ao sternal border. The second sound can, however, be made
Flow murmurs : (a) Pulmonary: Ejection systolic (drowned) out at the second left interspace or higher. It is widely
(b) Mitra! delayed dlas\ollc
split and variable with accentuated P2. A third sound may
PHO NO 51
. . ..
,
A2
11
P2
~ ... H
ESM
...,
be audible at the apex. A loud pansystolic murmur is
present at the left sternal border. The maximum intensity
of the murmur may be in the third, fourth or the fifth left
.
2 LIS
PSM intcrspace. It is well heard at the second left interspace
LLSB
., ,.~ ,DOM JW\11_,~ I . but not conducted beyond the apex. A delayed diastolic
murmur, starting with the third sound is audible at the
apex (Fig. 16.16).
The electrocardiogram in VSD is variable. Initially, all
patients with VSD have right ventricular hypertrophy.
Because of the delay in the fall of pulmonary vascular
resistance due to the presence of VSD, the regression of
Rg. 16.14: Summary of auscultatory findings In ventrlcular septal pulmonary arterial hypertension is d elayed and right
defect. 2 LIS second left lnterspace; LLSB lower left sternal border; ventricular hypertrophy regresses more slowly. In small-
PSM pansystollc murmur; DOM delayed diastolic murmur; ESM or medium-sized YSD, the electrocardiogram becomes
I
ejection systolic murmur. normal. In patients with VSD and a large left-to-right
shunt, without pulmonary arterial h ypertension, the
its volume is decreasing. The left-to-right shunt, therefore, electrocardiogram shows left ventricular hypertrophy by
streams to the pulmonary artery more or less directly. This the time they are 6-12 months old. There are, howev~r,
flow of blood across the norm.al pulmonary valve results no ST and T changes suggestive of left ventricular stra 1.0
in an ejection systolic murmur at the pulmonary valve. pattern. Patients of YSD who h ave either pulmonic
Disorders of Cardiovascular System I 413 -
cardiogram shows increased left atrial and vt-ntric'IJlarM;1.e
ns well as exaggerated mitral valve motlan. 20 edit> can
identify the number, site and size of defect almo~t all ca~
(Fig. 16.16), presence or absence of pulmonic sU..-n~r~I,; or
pulmonary hypertension and associated defects.
Assessment of Severity
If the VSD is small, the left-to-right shunt murmur
continues to be pansystolic but since the shunt is sma ll,
the second sound is normally split and the inU.-nsity of1'2
is normal. There is also absence of the delayed diastolic
mitral murmur. If the VSD is very small,itactsas a sumotic
area resulting in an ejection systolic murmur. This is a
relatively common cause of systolic murmurs in yo ung
infants that disappear because of the spontaneous cJ03urc.
If the VSD is large, it results in transmission of left
ventricular systolic pressure to the right ventricle. The
right ventricular pressure increases and the difference in
the systolic pressure between the two ventricles redua.>s.
Fig. 16.15: Chest X-ray in ventricular septal defect. Note the The systolic left-to-right shunt murmur becomes shorter
cardiac enlargement mainly Involving the left ventricle together and softer, and on the bedside is heard as an ejection
with Increased lung vasculature as suggested by the size and systolic murmur.
Increased number of end-on vessels in the lung fields Patients of VSD may h ave either hyperkinetic or
obstructive pulmonary arterial hypertension. The P2 is
stenosis or pulmonary arterial hypertension may show accentuated in both. In the former, there is large Jeft-to-
right as well as left ventricular hypertrophy or pure right right shunt whereas the latter is associated with a small
ventricular hypertrophy. The mean QRS axis in the frontal left-to-right shunt. In hyperkinetic pulmonary arterial
plane generally lies between +30° and +90°. hypertension, the cardiac impulse is hyperkinetic with a
The cardiac silhouette on chest X-ray is left ventricular pansystolic murmur and thrill, wide and variably split 52
type with the heart size determined by the size of the left- with accentuated P2 and a mitral delayed diastolic
to-right shunt (Fig. 16.15). The pulmonary vasculature is murmur. Obstructive pulmonary arterial hypertension is
increased; aorta appears normal or smaller than normal associated with a forcible parastemal impulse, the thri!J
in size. There may be left atrial enlargement in patients is absent or faint, the systolic murmur is ejection type, the
with large left-to-right shunts. Patients ofVSD with a small 52 is spilt in inspiration (closely split) with accentuated
shunt either because the ventricular defect is small or P2 and there is no mitral murmur. Thus, on the basis of
because of the associated pulmonic stenosis or pulmonary the assessment of physical findings, it is possible to
arterial hypertension have a normal-sized heart. Echo- separate very small, small, medium-sized and large VSD.
Fig. 16.16: Echocardiogram (right frame) with anatomic correlates (left) In membranous ventricular septal defects. This view Is a
Parasternal short axis view. f:vrow points to the VSD that Is partly closed by aneurysm of septal leaflet of the tricuspld valve. Ao aortic
root; IA left atrium; LVOT left ventricular outflow tract; RA right atrium, RV right ventricle; LAA left atrial appendage; STL septa!
t~cuspld leaflet: PA pulmonary artery
•
- 414 j Essential Pediatrics
H modynamfcs
Physluluglcnlly, lhc pulmonlc s tcnosis c:tuscs concentric
rihht \ll'nlrkulnr hypertrophy without c.m li.K' en largement
.rnd ''" lncn•,1st• In right ventricular prc~1-.urt• (Fig. 16.21).
Wlwn tlw right vcntrlcul.n pre~surt• is .1s hiHh .1s the left
\'cntrk 11ln1· or the nurtlc pressure, ,, right-to- left s hunt
11p1>1•.us t11 dccomprc.ss the right Vl'n tric l1·. Once the ri>;ht
.md left vcntrlcul.ir JHl'!-ISU rcs h.tvl' bl'corne idt•ntic.11,
incn.•.1sinH ~l~vcrlt y of p11lmn11ic s h·no 1.. rl'duccs the flow
of blood into the pulmon;iry artery .incl incrt'rl!IC'i the right·
to·ldt shunt . As the systol ic prc.,,.urt:s bctwcl'n the two
ventricles .m~ idcntic.ll, ttwrc j., litlf(• or no ldt-to-right
shunt .md tlw VSD is s ilent. ·nw ri~ht - to· lt·ft s hunt i'> .1 lso
Ag. 16.20: Angiogroms (oortogrom) obtained before and otter silent silll'l' it ocn1rs ill insignificnnl diH1·rcnn · in prc<>.'l urc
ro1 occlusion of o moderately lorge potent ductus orterlosus betWL'l'll tlw ri~hl ventricle .md lhc <1orta. 'Jltt.' flow from
(POA) showing complete occlusion the right vent ride into the pulmun.uy .utt•J')' 1xcurs <1cross
the pulnwnic stcnusis producing .in ejection sy~ tolic
CYANOTIC HEART DISEASE murmur. The more SC\ ere the pulmonic ~tcno<. 1 • the less
the flow into the pulmonary .ult.!ry .md the bigger the
Tetralogy of Fallot right·to-lcft shunt. Thus, the severity of cy.m~is i.s directly
Among cyanotic CHO, tetralogy of Fallot (TOF) has a proportional lo the severity of pulmonic s tcno -i , but the
relatively favorable natural history that allows survival intensity of the systolic murmur is in\'C r~ l y related to the
beyond infancy in about 75% of cases. As a result, it is the severity of pulmonic stenosis.
most common cyanotic CHO encountered beyond the age The VSO of TOF is always l.uge l'nough to olllow frt:c
of 1 year, constituting almost 75% of all patients. The exit to the right-to-left shunt. Since the right ventricle- is
physiology is that of VSO with pulmonic stenosis, as effectively decompressed by VSD, congc tivc failure
described above. Anatomically, it is characterized by the seldom occurs. Exceptions to this rull' .H\.' (t) ant•mir:l;
classic tetrad of severe right ventricle outflow obstruction, (ii) infective endocarditis; (iii) systemic hypt:rtcnsion;
large VSO, aorta that overrides the VSO and right (iv) right ventricular dysfunction from lung· t.rnd ing
ventricular hypertrophy. Multiple anatomical variations severe hypoxia, and (v) ao rt ic or tricu:.pid v.llve
exist, which influence treatment (Table 16.15). regurgitation.
- -
Table 16.15: Anatomic variations in tetralogy of Fallot
Structure Common variation Implications
Right ventricular outflow Degree of stenosis at various levels: Severe stenosis manifests early: nnnuku narrowing
tract infundibulum, valve, pulmonary requires correction with transannul!lr p,\lch with
annulus, main pulmonary artery stenosis significant late sequelae; prodominJnt vulvar
stenosis may allow palliation with b~lloon
valvotorny In selectod cases
Branch pulmonary arteries Stenosls of left pulmonary artery (LPA), Small branch PA may not allow surg.cdl cocrect1on
· (PA) absence of either branch PA, hypoplastic at oarly age; absent branch PA roquiro pla~mont
of PA conduit
Pulmonary valve Absent pulmonary valve with aneurysmal Sovoro airway compression; manitost:.ltiC>ns ch.efty
branch PA rosplrntory
Ventricular septal defect VSD extended to Inlet or outlet septum; Surgical oppro. ch needs to bo tnll rod
· (VSD) restrictive VSD with sovoro right
ventricular hyportrophy; nddltlonnl
muscular VSD
Coronary arteries Origin of loft onlorlor descending ortory Abnormal vossol comos In way of conechvo surgory
lrom right coronary ortory
i'
Atrial communication
Aortopulmonary collaterals
Atrial seplal dofocts, potent fornmon ovnlo
Ag. 16.21: Diagrammatic portrayal: (a) Ventricular septa! defect. (b) ventricular septa! defect with moderate pulmonlc stenosls,
and (c) Fallot's tetralogy. (a) In the absence of pulmonlc stenosls, the right ventricular (RV) and the pulmonary artery (PA) pressures
are normal or slightly elevated. Since the left ventricular (LV) pressure Is higher, there Is a systolic flow of blood from the LV Into the
PA through the RV. (b) If a VSD Is associated with moderate pulmonlc stenosls, the RV systolic pressure increases and there Is RV
hypertrophy. The left-to-right shunt decreases and the VSD murmur becomes softer. The pulmonlc stenosls murmur, however, is
loud. (c). In Fallot's tetralogy, the RV and LV pressures are Identical. There Is no left-to-right shunt and as such the VSD is silent. The
flow from RV to PA decreases, decreasing the Intensity of pulmonlc stenosls murmur. A right-to-left shunt occurs from RV to aorta
(Ao) at Identical pressures. As such the right-to-left shunt Is silent
The right ventricular outflow obstruction results in a Physical examination discloses cyanosis, clubbing,
delay in the P2. Since the pulmonary artery pressure is slightly prominent 'a' waves in the jugular venous pulse,
reduced, the P2 is also reduced in intensity. The late and normal-sized heart with a mild parastemal impulse, normal
soft P2 is generally inaudible in TOF. The 52 is, therefore, first sound, single second sound and an ejection systolic
single and the audible sound is A2. Since the aorta is murmur which ends before the audible single second sound
somewhat anteriorly displaced, the audible single A2 is (Fig. 16.22). The electrocardiogram in TOF shows right axis
quite loud. The ascending aorta in TOF is large and may deviation with right ventricular hypertrophy. T waves are
result in an aortic ejection click. On auscultation, the usually inverted in right precordial leads; P pulmonale may
diastolic interval is completely clear in TOF as there is no be present, but is uncommon. Vl may show pure R waves
third or fourth sound or a diastolic murmur. Concentric but transition to R/S complex occurs at V2. Chest X-ray
right ventricular hypertrophy reduces distensibility of the sho'_'Vs a norma.1-sized heart with upturned apex suggestive
right ventricle during diastole. The right atrial contraction of nght ventricular hypertrophy. The absence of main
at the end of diastole causes relatively large 'a' waves. pulmonary artery segment gives it the shape described as
However, these waves not too tall unless right ventricular
dysfunction is present. Tetralogy of Fallot
Sounds
Treatment
The medical management of TOF is limited to prevention
and management of complications and correction of
anemia. Oral beta-blockers help prevent cyanotic spells.
Maximally tolerated doses of propranolol ranging from
Fig. 16.23: Chest X-ray In tetralogy of Fallot with right aortic 0.5-1.5 mg/kg/dose should be administered. Iron
arch. The key findings are reduced lung vasculature as supplementation is recommended for all infants and
suggested by the dark lung fields, normal heart size, concavity young children with TOF. The management of anoxic
In the region of the main pulmonary artery (pulmonary bay]. spells is indicated in Table 16.13.
This X-ray also shows a right aortic arch. The arrow Indicates the
indentation of the right arch on the right side of the trachea
Definitive surgery for TOF involves closure of VSD and
relief of the right ventricular outflow tract obstruction.
Coeur en Sabot. The aorta is enlarged and right aortic arch is The relief of the obstruction might involve placement of a
present in 30% cases. The right aortic arch in a postero- transannular patch across the pulmonary valve resultino-
anterior roentgenogram is recognized by its concave in severe pulmonary regurgitation. There is growin~
impression on the right side of trachea. The pulmonary emphasis on retaining the pulmonary valve during initial
fields are oligemic (Fig. 16.23). repair to prevent pulmonary regurgitation and its major
The murmur shortens and the cyanosis increases with late consequences (RV dilation, arrhythmia, heart failure
increasing severity of the right ventricular outflow tract and sudden death). However, this is not possible, if the
obstruction. Paroxysmal attacks of dyspnea can be present pulmonary annulus is small.
with mild as well as severe TOF. However, effort Although definitive operation is feasible in youno-
. f , 0
intolerance is directly related to the severity. m ~1'.ts, so?1e centers opt for palliative options initially.
This is typically done through the Blalock-Taussio- shunt
Diagnosis which consists of subclavian artery-pulmonar; arten:
The diagnosis of TOF is confirmed by echocardiography; anastomosis using a Goretex graft. Alternatives includ~
cardiac catheterization is seldom necessary. Additional balloon dilation of the pulmonary valve or s tenting of
specific information required for surgical decision is also the patent arterial duct (if present). A number of long-
obtained through echocardiography. Cardiac catheteriza- term concerns have emerged in survivors of TOF repair
~on or CT /MRI may be required in older children with 2-3 decades after the operation. These include heart
hmited echo windows and in selected specific failure and risk of ventricular tachvarrhvthmias as a
circumstances (associated aortopulmonary collaterals, result of right ventricular dilation' that 'results from
uncertainties in coronary artery anatomy). chronic pulmonary regurgitation, as well as the scar on
the right ventricle, if ventriculotomy has been done
Course ond Compllcotlons during operation.
The pulmonic stenosis becomes progressively severe with
Trlcuspld Atresla
•
age, and dyspnea and increasing exercise intolerance limit
Patient activities. Each attack of anoxic spell is potentially Congenital absence of the tricuspid valve is called
fatal. Anemia, by decreasing the oxygen-carrying capacity tricuspid atresia (Fig. 16.24). The right ventricle is
Of blood, reduces the exercise tolerance still further. It can hypoplastic. The inflow portion is absent. The hemo-
result in cardiac enlargement and congestive cardiac dynamics is described above; see singl e ventricle
failure. Patients are prone to infective endocarditis. physiology.
Fig. 16.24: Tricuspid atresla: (a) Normally related great arteries. Systemic venous blood reaching the RA through the superior [SVC)
and inferior vena cava (IVC) reaches the lA through an atrial defect (or patent foramen ovale). There is complete mixing of the
systemic and pulmonary venous blood in the lA. The LV is large. Aorta [Ao) arises from the LV. A muscular ventricular septal defect
Is the only route through which blood can reach the hypoplastic right ventricle (RV Inf.). The pulmonary trunk (PT) arises from the right
ventricle. (b) Transposed great arteries with tricuspid atresia. The PT is arising from the LV whereas the Ao is arising from RV. lA left
artium; RA right artium; RPA and LPA right and left pulmonary artery; RV Inf. right ventricular infundibulum; RV and LV right and left
ventricle; SVC and IVC superior and inferior vena cava; RPV and LPV right and left pulmonary veins
Treatment
Surgical treatment consists in obliterating the atrialized
portion of the right ventricle and repairing the tricuspid
valve. The'cone repair of tricuspid' valve, which involves
mobilization of the displaced tricuspid annulus and
repositioning the valve at the level of the normal annulus,
is increasingly used.
fl~ ..,._. LA
RA
I
RV ....-. LV
I I
lV RV
I
AO ....-.
I
PA I I
PA AO
\ 6rC.I )
Rg. l 6.2S: ll'le route of 0.~'\.1 fiow in CCCl'\Pll:'.:!te TG.\ ~'\ll'ls In
two seporcte ciccu:~~;s and s1.ml\'CI ~<i's on rru.\Jng. lhe
mt\ing con cx.~ur at tN omcl 'ootricuklr cc groot '~~~ lev~.
Bronchlct ccilatero' (St. C~t.) cls0 inc~-:e ~ln"tcrtCry l'\'ocd
flow: In cortocted TGA, the !"Cut~ of b!o-..,'1 flow is notmat.
H~onan't.lcs d~x:l oo o..~'\..'X:icted cn...."·'<nc'f€s
Management
~urgery .is i~di.cated as early as possible since 80% of
mfants die w1thm the first 3 months of life, if not operated.
Obstructed TAPVC needs surgery at short notice. The
results of surgery for T APVC are good in most centers
but newborns and infants with obs truct ed TAPVC
son~etimes need a long time to recover after surgery. The~e
patients may develop pulmonary hypertensive crisis 1n
the postoperative period.
I
and High Pulmonary Flow
Apart from trans position of great vessels nnd t~tal
Fig. 16.31: Chest X-ray In unobstructed supracardlac total anomalous pulmonary venous connection, single ventricle
anomalous pulmonary venous connection to the lnnomlnate without obstruction to pulmonary blood flow, persistent
vein via the left vertical vein In an 8-year-old child. This Is the truncus arteriosus, tricuspid atresia with nbscncc of
characteristic figure of '8' sign or the snowman's sign obstruction to pulmonary blood flow nnd double outlet
Disorders of Cardiovascular System 1425 -
right v~tricl~ without pulmonic stenosis present with Eisenmenger Syndrome
0-anosis ~d increased pulmonary blood flow. Patients Sounds
present with ~ongestive failure in the neonatal period and S1: Normal jl'---111
are charaetenzed by cyanosis, cardiomegaly and failure
to thrive. Almost 80% die within 3 months of life due to
S2: ASD : Widely split and fixed
VSD: Single - ~
RAl~l
PDA: Normally split
congestiv: cardiac failure or pulmonary infection. Those P2: Accentuated
who surv_we devel~p pulmonary arterial hypertension. X: Constant
RV ......_ LV
Echocar~o~aphy is necessary to arrive at the specific S3: RV lnASD
diagnosIS. S~ce the mortality of unoperated patients is
S4: RAlnASD PA 191 Ao
his!1 ~~patients develop Eisenmenger syndrome early Murmurs ~erential
1
in life, it 15 necessary that patients presenting with cyanosis Pulmonary regurgitation (Graham-Steel!)
cyanosis
and increased pulmonary blood flow be referred to Ejection systolic ±
81 X
specialized centers as early as possible. S2 ESM
PHON0 11 - 111-o Ii .., ...
cyanotic Heart Disease with Early DM
Pulmonary Arterial Hypertension
Patients with Eisenmenger syndrome have severe
pulmonary arterial hypertension resulting in right-to-left
Fig. 16.33: Summary of auscultatory findings in Eisenmenger
shunt at the atrial, ventricular or pulmonary arterial level.
syndrome
Eisenmenger complex consists of pulmonary arterial
hypertension with a VSD providing the right-to-left shunt. pulmonary component of the second sound is accentuated
and louder than the aortic component. The splitting of
Hemod;nomlcs
the second sound remains wide and fixed in atrial septal
The pulmonary arterial hypertension is due to pulmonary defect. Due to superimposition of A2 and P2, the second
vascular obstructive disease. If a communication is present sound is single in patients who have a VSD. Patients who
at the pulmonary arterial level or the ventricular level, have a PDA continue to have a normally split second
the right ventricular pressure cannot go beyond the sound. A constant pulmonary ejection click, unlike in
systemic pressure. The right-to-left shunt decompresses patients of valvar pulmonic stenosis, is well heard both
the right ventricle. The right ventricle has only concentric during inspiration and expiration at the second left
hypertrophy without significant increase in the size. In interspace. A functional pulmonary regurgitation murmur
patients who have a PDA or VSD, there is only a mild can be present along the left sternal border. Patients with
parastemal impulse without significant heave. In patients atrial septal defect, in whom Eisenmenger physiology is
who do not have a VSD or PDA, the right ventricle besides uncommon, can develop tricuspid regurgitation (Fig. 16.33).
hypertrophy also dilates. The right-to-left shunt at the Electrocardiogram reveals right axis deviation and right
atrial level is an indication of right ventricular failure to ventricular hypertrophy, P pulmonale may be present. The
accommodate this volume and push into the pulmonary chest radiograph is characteristic, showing prominent
artery. Patients of Eisenmenger syndrome with pulmonary artery segment, large right and left main
communication at the atrial level only exhibit a parastemal pulmonary arteries and their branches, and oligemic
heave and cardiac enlargement. peripheral lung fields (Fig. 16.34).
A right-to-left shunt at the atrial level or the ventricular
level reaches the ascending aorta and is thus distributed Treatment
to the whole systemic circulation. This results in equal Ideally, pulmonary vascular obstructive disease should
cyanosis of fingers and toes. A right-to-left shunt through be prevented. This means early diagnosis and correction
a PDA is directed downwards into the descending aorta, of all CHO associated with increased pulmonary blood
Which results in differential cyanosis affecting lower limbs, flow. Patients with cyanosis and increased pulmonary
With pink upper limbs. blood flow develop Eisenmenger physiology very early
and need to be operated by 2-3 months of age. Medications
C/fnfco/ Features are available for the management of pulmonary hyper-
Patients present with history of cyanosis, fatigue, effort tension.
intolerance and dyspnea. There may also be histor~ of
repeated chest infections in childhood. On physical OBSTRUCTIVE LESIONS
examination, they have cyanosis and clubbing. Differential
cyanosis separates patients who have a PDA from those Aortic Stenosis
~ho have a VSD or atrial septa! defect. The fea~ures Pathologically, the site of obstruction may be at valve level,
lndicative of pulmonary arterial hypertension consist of above the valve (supravalvar) or below the valve
Parasternal impulse and palpable second sound. The (subvalvar). At the valve level, aortic stenosis (AS) results
............ 426
~
I ---------~~~~------~~E~s~a~e~nt~la~l~P~e~~e~t~rl~cs!!..---~----------~~~~~---~
ventricular hypertrophy, t~1e left ventricular diastolic
,
pressure a l"o
" ri ses. With increase
. in left ventricula
. r
1
diastolic pressure, the left <1tria P.rcssd~re m ust increase to
be able to fill the left ventricle during iasto1e. Hence, With
severe AS accompanied with. marked l~ft ventricular
hypertrophy, a forceful left <1tnal contraction results in a
palpable as well ns nu?i.blc ~ourth sou~d (S4). When the
left ventricle sta rts foiling m AS, ~cs1des ~ypertrophy
d ilatation also appears nnd causes increase m heart size
and an audible third so und (S3). In valvar AS, there is
post-stcnotic dilatation ~f ascending aorta, seen on
posteroantcrior chest rad1ograph. In supra~alvar and
subvalvnr AS, this is absent. In valvar stenos1s, the first
sound is followed by an aortic ejection click that precedes
the stnrts of the murmur; the click is heard at the apex,
and along left sternal border.
Cllnlcal Features
Patients with mild to moderate AS are asymptomatic. With
severe stenosis, the initial symptom is generally dyspnea
Fig. 16.34: Chest X-ray in Eisenmenger syndrome following on exertion. The patients may also give history of angina
ventricular septal defect. The proximal right pulmonary artery Is on effort and syncope. Presence of any one of these three
enlarged . There Is a relative paucity of vasculature In the symptoms suggests severe AS. The blood pressure is
periphery with a sudden tapering of caliber of the right normal with mild disease; the width of pulse pressure
pulmonary artery [pruning)
relates inversely with severity of AS resulting in low
amplitude prolonged duration pulse. Cardiac size remains
from either unicuspid or a bicuspid aortic valve. Rarely the normal unless left ventricular failure is present. The apical
aortic valve annulus may itself be small. 5upravalvar aortic impulse is forcible or heaving. In severe AS, the fourth
stenosis results from obstruction in root of aorta, above the sound may be palpable. If left ventricular failure is present,
aortic valve, as in Williams syndrome. 5ubvalvar aortic the 53 may be palpable. A systolic thrill is palpable at the
stenosis may be discrete (membranous), fibromuscular or second right interspace, suprasternal notch and the carotid
muscular (hypertrophic obstructive ccUdiomyopathy). arteries. 51 is normal and followed by an ejection click in
valvar aortic stenosis. The aortic component of the second
Hemod(nam/cs
sound (A2) is delayed but not diminished in intensity in
Valvar obstruction is overcome by raising the systolic AS. The delay results in closely split, single or paradoxically
pressure of the left ventricle. This is brought about by split second sound according to the severity of obstruction.
concentric hypertrophy of the left ventricle. Because of a With severe AS, 54 is audible, while in patients with left
powerful, muscular left ventricle, the emptying of the left ventricular failure, 53 is palpable and audible. The ejection
ventricle is complete but the duration of the systole is systolic murmur starting after the ejection click re.Khl>S a
prolonged. The prolongation of left ventricular ejection peak in mid-systole (Fig. 16.35). With increasing se,·erity,
time causes delayed closure of the aortic valve resulting the peak gets delayed so that the maximum intensil ,. of the
in delayed A2. Flow across the obstruction results in the murmur is closer to the end rather than being midsystolic.
aortic ejection systolic murmur that is typically diamond With immobile valves, due to fibrosis or calcification, the
shaped, starting after the first sound and ending before systolic click as we11 as A2 d iminish in intensity and may
the aortic component of the second sound with a mid- become inaudible (Fig. 16.36).
systolic peak. The systolic murmur is always palpable as Subvalvar AS is distinguished by absence of ejection
a thrill at the second right interspace, suprasternal notch click and post-stenotic dilatation of the ascending aorta
and the carotid vessels. The powerful left ventricle can on X-ray. An aortic regurgitation murmur may be audible.
maintain a normal forward cardiac output. The prolonged The maximum intensity of the systolic murmur and thrill
ejection results in a characteristic pulse that is best is in the 3rd or 4th left interspace. Supravalvar AS
described as slowly rising to a peak that is sustained and (Williams syndrome) is associated with elfin fades, ment~
then has a slow down slope. The peak is low so that the retardation, dentnl abnormalities strabisrnus an
pulse is of low amplitude and prolonged duration. peripheral pulmonic stenosis. Since ' the obstruction is
Concentric hypertrophy of the left ventricle results in above the aortic valve, the pressure in the segment of aorta
decreased distensibility of the left ventricle in diastole- before the obstruction is elevated and results in loud A2·
red uced compliance. In severe AS with marked left The jet through the supravalvar narrowing may be
Disorders of Cardiovascular System
1427 -
Aortic Stenosls
sounds LV
51-Nonnal
S2-A2 Delayed
P2 Normal
Nonna! splitting single
Paradoxical splitting
53: With LV failure
54: Severe stenosis .....
'
. Murmurs
Ejection systolic (Diamond shaped)
(INSP)
(EXP)
11
S4
111 •
.,
S1X ESM A2P2
I• . . II
S2
P2A2
q
Mild
Moderate
Severe
LA
- - --- -:- '
I
I
ESM
Ag. 16.35: Summary of auscultatory findings In aortic stenosfs.
54 fourth sound; X aortic click Fig. 16.36: Aortic stenosis: Diagrammatic portrayal of the
hemodynomic basis for aortic stenosis murmur. The first sound
directed toward the innominate artery resulting in higher (Sl) occurs as the left ventricular (LV) pressure increases above
systolic pressure in the right arm compared to left. left atrial (LA) pressure. Thfs Is followed by the ejection click (X)
The electrocardiogram reveals left ventricular occurring after the aortic valve opens. The shape of the gradient
hypertrophy. Presence of ST and T wave changes suggest between LV and aorta (Ao) corresponds to the shape of the
severe disease (Fig. 16.37). However, a normal electro- aortic ejection systolic murmur (ESM). The murmur ends before
cardiogram does not exclude severe AS. Chest X-ray the aortic components of the second sound (A2)
mi E·.:~. ·i:: . : - · ::: :: :: ·:. J : :.: : : .;..:.~· 1 = :::· ~ ;::: ·=· ,..J . .. :
Ll,f: 1, =--
!i.t ·~·
. .· .!l,::.~ :..i:..·; :.~. ·.:; ~.:. :. .~:. ~. ;. ~.;.:, ;. ~.>.~;. :.::.~:. ~.:. ~.: >_,l, :. :.~..:· ::·.: .. : : :. :·: .
:::; :::: ::" .:.
:'.
::·i
fgj 1~ : ~~~~~!ii~: ~~i~ ~j ~ '·-·· .... ::: :;:. ~=- :;:: ~:=: ::
.,1
- 42a I ~------~~~~~------~!E~s~se~n~t~ia~l!P~ed~la~tn~·cs=~--~~------~~--~~~~~----
d" 1 wall is spared. It may be distal or
sh ows a no rmal-sized heart with dilated ascending aorta aorta; the me ta ligamentum arteriosus and also
in valvar AS. In supravalvar and subvalvar stenoses, the · al to the ductus or . . .
proXlill b 1 ·an artery. A bicuspid aortic valve 1s a
thoracic roentgenogram may be normal. Pres~nce of the left su c av1
cardiac enlargement indicates severe AS. Echocardio~am common association.
can identify the site of stenosis, and assess the gradient
Hemodynamlcs
across the obstruction accurately.
In fetal life, the right ventricular output p_asses into the
Assessment of Severity a through the ductus artenosus. The left
descending aort . · 1 ft ·
The severity of AS is determined, based on the following ventricular output empties into th~ mnorrunate, e carotid
and left subdavian arteries and little output ~eaches the
i. Symptomatic patients have severe AS; lack of
descending aorta. The portion of the aorta dIStal to the
symptoms does not exclude severe disease.
left subclavian and before the portion w.here th~ ductus
ii. Narrower the pulse pressure, the more severe the AS.
·
artenosusJ ·0 ;..........,.., 15
· called the isthmus. At birth,
. the ISthmus
iii. Systolic thrill at second right interspace suggests at
is the narrowest part of the aorta: Following closure. of
least moderately severe AS.
theocd tus arteriosus, the descending aorta 'th
must receive
din
iv. The later the peak of the ejection systolic murmur, the
its total supply from the left ventri.cle via e ascen g
more severe the narrowing.
aorta. Neonates with severe coarctation, therefore, become
v. Delay in A2 correlates well with severity. With mild symptomatic immediately as _the duct starts to close.
AS, the S2 is normally split; with moderate AS, it is
However, a significant proportion pres~nt l~te.
closely split; with severe or critical AS, it is single or
The exact cause of systemic hypertension IS not known;
paradoxically split.
aortic obstruction is partly responsible. The narrow ?u~e
vi. Presence of 54 is indirect evidence for severe AS.
pressure in the descending aorta ~istal to coarcta~on JS
vii. Presence of S3 indicates severe AS and congestive implicated in the renal mechanism for causat10n of
cardiac failure. hypertension. The obstruction stimulates growth of
viii.ST and T changes in the electrocardiogram suggest collateral vessels between the proximal and distal
severe stenosis. segments. The intercostal vessels also participate in
ix. Cardiac enlargement on chest radiograph indicates decompressing the hypertensive upper segment. They
severe AS with left ventricular failure. enlarge and become palpable at the lower borders of the
x. Doppler can quantitate the gradient across the aortic ribs. Palpable collaterals are also felt at the medial and
valve accurately. Two-dimensional echo reveals inferior angle of scapula. Because of the decompression
concentric left ventricular hypertrophy; ventricular of upper segment by collaterals, the resting blood pressure
dysfunction is associated with heart failure. in upper extremities may be normal, but rises on exercise.
Treatment Cllnlco/ Features
Patients with AS should be followed closely, with 6-12 Coarctation has a continuum of severity and the age at
monthly electrocardiogram. Symptoms should be presentation is linked to severity. Newborns with severe
carefully evaluated. Doppler echo can be used to coarctation present as soon as the duct starts to close.
quantitate the gradient at each visit and ventricular Infants with coarctation present with left ventricular
function is monitored. Severe AS is risk for sudden death. dysfunction and heart failure. It is important to examine
Patients should be discouraged from outdoor games, femoral pulses in newborns and infants with heart failure.
athletics, competitive sports and strenuous exercises, if Later in life, coarctation is often not associated with
AS is significant (gradient of >50 mm Hg). symptoms.
Balloon aortic valvuloplasty is the procedure of choice The only symptoms in uncomplicated coarctation may
for valvar AS. A balloon introduced through the femoral be intermittent claudication, pain and weakness of legs
artery can be placed at the aortic valve and inflated to and dyspnea on running. Examination shows delayed and
tear the valve along the commissure. It is indicated, if the weak femorals and strong brachia} arteries. The heart size
gradient is above 75 mm Hg. Supravalvar and subvalvar remains normal with a forcible or heaving left ventricular
AS do not respond to balloon dilation; the procedure apex. A systolic thrill may be palpable in the suprasternal
should also be avoided in patients with significant aortic notch. There are prominent arterial pulsations in th~
regurgitation. Surgical options include aortic valve repair suprastemal notch and the carotid vessels. The first sotlll
,,
(!nap and Exp)
(Exp) S4
I •I
• 52
Moderate
Severe
Age and sex: The incidence of rheumatic fe\ er following
streptococcal throat infection is 0.3% in the generill
population and 1 to 3% in presence of epidemics of
streptococcal pharyngitis. The illness commonly affects
those between 5 and 15 years of age; first episodes are
rare before 3 years or after 30 years age. Although the sexes
Fig. 16.39: Summary of ouscultotoryflndlngs In pulmonlc stenosls are nearly equally affected, mitral valve disease and chorea
is more common in girls whereas aortic valve involvement
is often seen in boys.
regurgitation may appear. Since the right atrium offers
less res istance to flow of blood than obstruction at the Predisposing factors: Poor socioeconomic conditions,
pulmonary valve, the flow through the pulmonary valve unhygienic living conditions and overcrmvding pre·
diminishes reducing the intensity as well as the duration dispose to streptococcal infections.
of ejection systolic murmur.
Etiopathogenesis
The elcctrocnrdiogrnm shows right axis deviation and
right ventricular hypertrophy, suggested by pure R waves The etiology of rheumatic fever is unknown. A strong
or qR complex in V4R and VJ lends. P pulmonale suggests ~s~oci.ation with beta hemolytic streptococci of group A
severe PS. Chest X-rny shows a normal-sized heart with is indicated by a number of observations:
normal pulmonary vnsculature in mild, moderate as well i. History of preceding sore throat is available in 50%
as severe PS. Pulmonary oligemia occurs, if the patients patients; more than 85% show elevated levels of anti·
develop a right-to-left shunt at the atrial level in severe or streptococcal antibody titer.
critical PS. The main pulmonary artery exhibits post- ii. Epidemics of streptococcal infection are followed by
stenotic dilatation. Echocardiography can identify the site higher incidence of rheumatic fever.
and severity of obstruction and helps in planning catheter iii. The seasonal variation of rheumatic fever and
intervention. streptococcal infection is identical.
iv.~ p~tients with established RHD, streptococcal infec·
Treatment hon is followed by recurrence of acute rheumatic fever.
Valvar PS generally does not increase in severity with v. Penicillin prophylaxis for streptococcal infection
time unless it is severe or diagnosed in the newborn prevents recurrences of rheumatic fever in those
period. Patients with mild PS (gradient of 50 mm Hg or patients who have had it earlier.
less) need annual review. Balloon pulmonary Streptococci have never been isolated from rheumatic
valvuloplasty is the treatment of choice for isolated lesions in joints, heart or the bloodstream. Rheumatic fever
valvnr PS. The procedure is sometimes technically appears to be the result of the host's unusual response at
challenging in newborn with critical PS. Surgical both the cellular and hurnoral level to Streptococc11s
treatment is indicntcd only if balloon valvotomy is (Fig. 16.40). Following streptococcal sore throat there is a
unsuccessful, as in pntients with dysplastic valves or latent period of 10 days to several weeks befor~ the onset
smnll pulmonnry valve annulus. of rheumatic fever. Str.eptococcal cell wall proteins as well
as carbohydrates may induce production of antibodies that
Suggested Reading are capable of reacting with human connective tissue,
• Alll' n HO, Shnddy RE, Driscoll DJ, Pcltes TF, Moss Adnms' Heart
resulting in rheumatic fever.
discnsc In lnfnnl'!l, children nnd ndolescents, 8th Edition, Kluwer/ Only heart valves a~e permanently damaged d.urin~
Lippincott Wllllnm nnd Wilkins, Phllndelphin, USA, 2012. an episode of rheumatic fever. All other affected tissue
,,.-------~--------------~----.!D~l~s~or~d~e~rs~o~f~C~a~rd~l~ov~a~e~c~u~le~r~S~y!st~e~m~~--------~~~--- I 4a1
~
STAGE1
lmmuno rocognltlo~
.
~
Rheumatoganlc
. -+
MA--
Pharyngitis
streptococci
STAGE 2
lmmuno coll circulation
Cytoklno reloaso IL-2, TNF-rt, others
STAGE 3
Antibody
attachment
Molecular mimicry
...------; lg . - -
Yy y v~
STAGE4 Immune
T cell recruitment mechanisms
CD4and COB
Infiltration
~
T cells respond to other
Epitope spreading
Neovascul~rlzatlon •
STAGE 5 cardiac a-helical proteins
• including tropomyosin and
T cell recruitment vimentin
Fig. 16.40: Pathogenesis of rheumatic fever. It Is proposed that the endothelium suffers initial damage due to a humeral immune
response, the damage resulting In vascular cell adhesion molecule l (VCAM- l J being expressed on the endothelium. This is folloNed by
activation of cellular Immune response. N. a result CD4+, CDS+ Tlymphocytes and macrophages get attached to the valvar endothelium
and migrate to the connective tissue core. This sets up an inflammatory response. The inflammation is accompanied by neovascularization
of the valve substance. IFN-y Interferon gamma, TNF-cx tumor necrosis factor alpha, Th l Thelper cells l
This is a soft delayed diastolic mitral murmur heard movement. It is an early manifestation and occurs in
transiently during the course of acute rheumatic fever 70-75% of cases according to western literature. Howe\'et,
possibly as a result of flow across the inflamed and the figures from India indicate that arthritis is seen in
thickened mitral valve. 30 to 50% of patients. The pain and swelling appear rather
Endocarditis is represented by a pansystolic murmur quickly, last 3 to 7 days and subside spontaneously to
of mitral regurgitation with or without an associated appear in some other joint. There is no residual damage
aortic regurgitation murmur. Pathologically mitral valve to the joint. Arthritis tends to be commoner in older
is involved in all cases of rheumatic fever with carditis. patients.
Clinically, however, 5-8% patients may present as pure
aortic regurgitation. Thus almost 95% patients will have Subc11ta11eo11s nodules: Subcutaneous nodules appear on
mitral regurgitation murmur, a quarter of them also have bony prominences like elbows, shins, occiput and spine.
an aortic regurgitation murmur and only 5% present as They vary in size from pinhead to an almond. They are
pure aortic regurgitation. Tricuspid valvulitis resulting non-tender. Subcutaneous nodules are a late manifestatitm
in tricuspid regurgitation occurs in 10-30% of cases. and appear around 6 weeks after the onset of rheumati~
Isolated tricuspid valvulitis as a manifestation of fever though they have been described as earlv as 3 wee~
rheumatic endocarditis does not occur. Clinical evidence from the onset. They occur in about 3 to 20°/o of casei of
of pulmonary valve involvement in acute rheumatic fever rheumatic fever in India. Pa ti en ts who have subcutaneo~
is never seen. The acute hemodynamic overload resulting nodules almost always have carditis. They last from a feii
from acute mitral regurgitation and/ or aortic days to weeks but have been known to last for almost 3
year.
regurgitation leads to left ventricular failure and is the
main reason for the morbidity and mortality of rheumatic Cliorea: Sydenham's chorea is also a late manifestatio!I
fever and RHD. occurring about three months after the onset of acutt
Subclinical carditis: Carditis may occasionally be clinically rheumatic fever. Generally, by the time a patient mani~~
silent and only identified by echocardiography that shows chor~a, the si~ of inflanunation usually subside. CM~~
mitral regurgitation. ~ons1sts of serm-purposeful, jerky movements resulllll,
m deranged speech, muscular incoordination, awk\\'•1iJ
Artl1ritis: Rheumatic arthritis is a polyarthritis involving gait and weakness. The affected child is emotion3ll~
large joints that include knees, ankles and elbows. disturbed and drops things she or he is carrving. It is tll!\'
Uncommonly smaller joints may also be involved. It is a to four times more common in females a~ compal'l"i 11.:
migratory polyarthritis with the affected joints showing n:ales. Untreated, it has a self-limiting course of l'\,·o ~
redness, warmth, swelling, pain and limitation of stx weeks.
j 433 -
E-r1J1ema
1
:r· . marginatuni·• It is · an ear1v man1"festation
. cannot be equated with diagnosis, since this may happen
p redommantl)r seen th
over e trunk. It starts as a red spot
J I
with asymptomatic carriers.
\ \'ith a pale center m·ereasmg
•
1
· m· size
. to coa 1esce with.
aclja~t.spots to form a serpiginous outline; the rash in Eclrocardiograplty: The recent revision of Jones criteria
non-itching.
. . Recogru·tion
. of s kin m anifestations
· may be now includes echocardiographic findings for the diagnosis
difficult m dark-skinned patients. of rheumatic carditis. Features suggestive of rheumatic
carditis include annular dilatation, elonga tion of the
Mjnor Criteria chordae to the anterior leaflet of the mitral valve causing
Clinical criteria a prolapse and lack of coaptation of the two leaflets
resulting in mitral regurgitation. There is focal nodular
Freer: Rheumatic fever is almost always associated with
thickening of the tips of the mitral leaflets; they however
fever. The temperature rarely goes above 39.soc.
do not show the independent chaotic movement seen with
Arthralgia: ~algia is a subjective pain whereas arthritis infective endocarditis. Occasionally, the tip of the mitral
~eans su~1echve_ symptoms and objective signs of valve leaflet is flail because of chordal rupture resulting
infl~ati_on. w;ruie arthritis is a major manifestation, in severe mitral regurgitation. The left atrial and
~algia 15 a mm?~ manifestation. Figures from India ventricular size is increased. Involvement of aortic valve
mdicate that arthritis and arthralgia together occur in is recognized as aortic regurgitation.
about 90% of the patients Echocardiography has improved recognition of carditis,
which at times is not possible on auscultation. This has
Previous rheumatic fever or rheumatic heart disease: This lead to the recognition of subclinical carditis, characterized
criterion applies only for recurrent episodes of rheumatic by no clinical but echocardiographic findings of rnitral
fever. regurgitation. While the course of patients with subclinical
carditis is not clear, most patients are advised long-term
Laboratory manifestations
penicillin prophylaxis.
Acute phase reactants: The leukocyte count usually lies
between 10000 to 15000/cu mm. The sedimentation rate Treatment
is elevated during acute rheumatic fever and remains so
for 4 to 10 weeks in almost 80% patients. In a small Management is symptomatic combined with suppressive
proportion of patients, it may remain elevated even therapy.
beyond 12 weeks. Although congestive cardiac failure Bed rest: Bed rest is generally recommended for acute
tends to bring the sedimentation rate down towards rheumatic fever. Prolonged bed rest (>2- 3 weeks) is
nonnal, it is unlikely that patients of acute rheumatic fever seldom necessary unless there is clinically apparent
with congestive failure will have a normal sedimentation carditis with heart failure.
rate. C-reactive protein is elevated in all patients of acute
rheumatic fever, and subsides rapidly if the patient is Penicillin: After obtaining throat cultures, the patient
treated with corticosteroids. While absence of raised C- should receive penicillin. A single injection of benzathine
reactive protein is against the diagnosis of rheumatic fever, penicillin is given when the diagnosis of rheumatic fever
its presence is non-specific. is made. Penicillin V (250 mg four times a day for 10 days)
is an alternative; erythromycin (250 mg four times a day
Prolonged PR interval: Prolonged PR interval can get for 10 days) is given to those with penicillin allergy.
prolonged in many infections, nor is diagnostic of carditis.
Higher grades of block like second degree atrioventricular Suppressive Therapy
block especially Wenckebach type may be seen. Complete Aspirin or corticosteroids are given as suppressive
atrioventricular block is extremely rare. therapy. Since untreated rheumatic fever subsides in
12 weeks in 80% of the patients, either of the two
Essential Criteria suppressive agents is given for 12 weeks. Steroids are a
These include evidence of recent streptococcal infection. more potent suppressive agent as compared to aspirin.
Elevated levels of antistreptolysin 0 (ASO) indicate However, there is no proof that the use of steroids results
previous streptococcal infection and not rheumatic f~ver. in less cardiac damage as compared to aspirin. A number
Although generally the higher the level the more hkely of observations indicate that steroids act faster and are
one can conclude a recent infection, lower levels do not superior at least in the initial phases. Pericardia! friction
exclude a recent streptococcal infection. A basal ASO titer rub tends to disappear within three to five days after
of 50 U / dL that goes up to 250 U / dL is indicative of recent starting the steroids. Subcutaneous nodules also resolve
streptococcal infection. Rising titer of ASO is a strong faster with use of steroids. Patients who have carditis with
evidence for recent infection. congestive cardiac failure have a higher mortality if aspirin
Positive throat culture for streptococci, at diagnosis of is used compared to steroids. In selecting the medication,
rheumatic fever, is uncommon. A positive culture also the following guidelines are followed:
• 434 I Essential Pediatrics
·- I ~
recurrences. The role of systemic vasodilators, most
commonly ACE inhibitors and calcium channel blockers,
to reduce afterload in isolated MR and aortic regurgitation
is controversial. An important additional consideration
in RHO is the presence of varying degrees of mitral
stcnosis that accompanies MR
There are no clear guidelines for the timing of mitral
valve surgery (particularly replacement) in children.
Persistent symptoms, in spite of maximally tolerated
medications, warrant consideration of surgery especially
in the presence of pulmonary artery hypertension. For an
-----~- ---------
Disorders of Cardiovascular System I 441 11
valves, Incidence of embolism is high since the fungal of fingers or toes due to obstruction of blood supply.
vegetations te nd ti> be very large. Despite intensive Damage to the vasa vasorum of blood vessels due to
therapy, mortality fr; high, vasculitis may result in the formation of mycotic aneurysms
that can rupture and result in massive bleeding. The
t.at>oratory Olagno: I$ kidneys suffer from embolic infarct with hematuria and
Blood culture is ~A.mtial for diagnosis. A positive blood focal or diffuse membranoproliferative glomerulonephritis
culture in a patient with underlying heart disease, resulting in albuminuria and microscopic hematuria. The
5u.~pe.cted to have cnd~ rditis Ls confirmatory. 1hree sets findings of IgG, IgM and complement deposits on the
o( cultures, each containing adequate volumes of blood, glomerular basement membrane indicate that it is an
takt>n every half-hour are appropriate and detect 95% immune complex nephritis. Renal insufficiency tends to
cafAffl. 'flic rommoncst cause for negative cultures is prior appear beyond three weeks of the onset of endocardi tis and
antibiotic therapy or unsatisfactory culture technique. is progressive until the endocarditis is cured; hematuria
Jnfccti1m with unus ual organisms, anaerobic organisms can persist for 3-6 months. Even advanced renal
and fungi require special mediums and incubation for insufficiency tends to regress and renal function returns to
2-3 weeks. Arterial sampling does not offer any advantage normal after the endocarditis has been cured.
over venous sampk:.s. Other investigations, which provide
supportive evidence for the diagnosis, include: (i) normo- Treatment
cytic normochromic anemia, (ii) moderately elevated total The principles of management consist of: (i) identification
leukocyte count, OH) reduced platelets, (iv) elevated of organism and its antibiotic sensitivity; and (ii) prompt,
sedimentation rate and C-reactive protein, and (v) micro- appropriate and prolonged antimicrobial treatment to cure
scopic hematuria and albuminuria. and prevent relapse. If the blood culture is positive, the
choice of antibiotics is dictated by the antibiotic sensitivity.
Echocardlography If the culhlre is negative, empirical therapy covering a
&hocardiography is a valuable diagnostic tool, especially wide range of organisms is necessary. If the culture is
in patients with culture negative endocarditis. positive, the culhlre plate should not be discarded. After
Complications like ruptured chordae, perforated cusps starting the antibiotic treatment, patient's serum diluted
and flail cusps can be identified. Vegetations more than to 1:8 parts or more should be used to determine if it
2 mm can be identified on echocardiography, but its inhibits the growth of the organism in subculture, to
sensitivity is dependent on the site of involvement. For indicate the efficacy of treatment. Common organisms
aortic and mitral valves, the sensitivity is more than 90%, causing endocarditis, antibiotic of choice and duration of
while for tricuspid and pulmonary valves, it is 70%. The treatment is shown in Table 16.18. Over the last 2-3
presence of vegetations has high negative as well as decades are, the threshold for surgery for treatment of
positive predictive value for confirming the diagnosis of endocarditis is lowered considerably. Surgery is indicated,
infective endocarditis. Transesophageal echocardiography if response to antibiotics is suboptimal, in presence of large
is useful for diagnosing prosthetic valve endocarditis and vegetation, damage to valve apparatus with severe or
valve ring abscess. refractory heart failure and for fungal endocarditis.
Fu11gal endocarditis: Fungal endocarditis is resistant to
Complications therapy. Therefore, after 2 to 3 weeks of appropriate
Damage to valve cusps or perforation and rupture of treatment (amphotericin B), the patient should be operated
chordae tendinae might result in acute regurgitant lesions to remove the fungal mass. The antifungal agents should
and hemodynamic deterioration. Migration of vegetations be continued postoperatively for a minimum of 6 weeks.
may result in embolic neurological deficit, renal infarcts Relapse following apparently successful treatment can
With hematuria, mesenteric infarct and melena, and loss occur even up to 2 years.
...
, ·- ~,
Organism
-
Table 16.18: Choice of antibiotics and duration of treatment for infective endocarditis
Option I Option II Duration, weeks
Streptococcus viridans Penicillin, aminogfycoside Ceftriaxone, aminoglycoside 4
Group A streptococci Penicillin, aminogfycoside Ceftriaxone, aminoglycoside 4
Streptococcus faecalis Ampicillin, aminoglycoside Vancomycin, aminoglycoside 4-6
Staphylococcus aureus
Cschertchla coli
· Pseudomonas spp.
Cu~re negative
Cloxacillin/cefazofin, aminogfycoside
Ceftriaxone, aminogfycoside
Ticarciffin, aminoglycoside
Ampicillin, aminogfycoside
Vancomycin, aminoglycoside
Ampicilfin, aminoglycoside
Meropenem, aminoglycoside
Ampicillin, aminogfycoside
6
6
6
6
Ill
The choice of antibiotics should ideally be guided by culture results and organism sensitivity
Culture rregatitir. eudomr<litis: Pnth.mts with culturn
negative endocarditis need to be h'C'ah.~d t'mpll'lrnlly. Th'
choice of treatment is ctictatt'd h )' c\rc\lm~tn1H:u~
anticipating the !l'1ost likely <wganism. lf th~ pntlt•nt St'('K8
help late and has significnnt rrnal insufficlcnl:\', the
medication dose might need to be modlfiNi. ·
Prophylaxls
There have been mnjor changes in thl' rt'romnwndations
for prevention of endocarditis. Path'nts with rong{'nitnl
heart defects such as ventricular st'ptal dl'ft'ct. bil'uspid. Suggostod Roadlng
aortic valve and valvar pulmonary skrn)sis dn not • \Vll:;lll\ \V, T1111lw1'1' "''· ( •l'WllZ M, cl nl. l'rcvcnllon or inl~cli~t
routinely require prophylaxis. Accord.in~ t() lht' ~ulctclhws ''IHlol.'nl'lllll ~. C:uldclllwi< fl'om /\mcrkrm l lc.1rt Assuct,11111n
of the American Heart Association, sinct' tlw absolnte Cll'rnllllhm 2Ll07;t l6(l!i):17'.'(i-5·1.
lifetime risk of endocarditis is small, proph~·laxis is only
recommended for patients with conditions assnciah.•d with .MYOCARDIAL
. DISEASES
increased risk of adverse outcome from l'thinrarctitis Myocardltls
(Table 16.19). The focus of prophylaxis has shifted from
prophylactic antibiotics for a d ental pro('edure to the Myocnrditis is ..:hidly cnuscd by ECHO, Coxsackie B,
prevention of dental caries, which reduces the incidence rubella, herpes nnd influcnzn virnses. Diphtheritic
of bacteremia from daily activities and is, therefore, more myocnrditis is O('Cnsionnlly noted in South Asi<1. The
important. These guidelines need va\icfotion in d<.' vcloping prcscntntion may be abnipt, with cnrdiovnsculllr collapse,
countries where oral hygiene is unsatisfactory and regular or insidious devl'lopmcnt of henrt failure. Arrhythmias
dental health screening is not instituted in the majority. nnd conduction disturbnnccs may be present. Examination
Antibiotic recommendations for those who need shows cnrdiilc cnlnrgcmcnt, tachycardia, muffled heart
prophylaxis are as follows: sounds nnd fc.1tures of congestive cardinc failure. The
clectrncardiogrnm shows low voltages, and nonspecific
Dental Treatment ST-T changes. Chest X-ray rcvenls cardiac enlargement
i. Penicillin V 2 g given orally on an empty stomach with pulmonary venous congestion.
1 hour before dental treatment, followed by 0.5 g every Treatment includes management of congestive failure.
6 hours for 3 days, or Digoxin should be used cautiously, preferably in half to
ii. Crystalline penicillin G 1,000,000 U mixed with 600,000 three-quarters the standard dose. Steroids me of uncertain
U of procaine penicillin 30-60 min before dental ~nl~tc. and should be avoided during acute viremi<1. ACE
treatment, followed by oral penicillin as above, or ~nh1b1tors nrc a .usc.ful adjunct to therapy. The utility of IV
iii. Single dose of amoxicillin 50 mg/kg omlly 1 hour mununoglobuhns 1s not proven. Severe heart failure may
before the procedure require ndmission in an intensive care unit and mechanical
iv. Patients with prosthetic heart valves: Injectable ventilation. A vnrinblc proportion of children with
penicillin with streptomycin or gentamicin IM 1 hour myocnrditis recover completely.
before the procedure.
Cardlomyopathles
Genitourinary and Gastrointestinal Procedures
The term cardiomyopathy is an intrinsic disease of the
i. Amoxicillin 25 mg/kg by mouth 1 hour before, with myocnrdium which is not associated with a structural
gentamicin 2 mg/kg IM 30 min before procedure; both deformity of the lw<~rt. It is considered primary cardiorny~
pa thy when the etiology is unknown, and secondary, 1f
Table 16.19: Co~ditlons where antibiotic prophylaxis Is the myoc~rdi~l discnse is attributed to a systemic disease.
· definitely recommended ~yocar~rn.l diseases arc classified clinically as (i) dilated,
Prosthetic cardiac valve; prosthetic material used for valve repair (11) restnchvc, nnd (iii) hypertrophic cardiomyopllthY·
Past history of infective endocardltls A significnnt propmtion of patients have correctible
causes of left ventricular dysfunction that mimics dilated
Uncorrected cyanotic heart disease, palliative shunts and
cardiomyopnthy (Table 16.20).
I
conduits
During first 6 months following complete surgical repair of Dilated Cardiomyopothy
congenital heart disease
Dilated cnrdiomyopathy (DCM) is the commonest forJ11
Repaired congenital heart disease with residual defects at or of myocardinl disease. The onset of cardiac failure Jtl3Y
adjacent to the site of repair · 'd'1ous. C ar d iomegaly and 53 ga11optare
b e ncute or ms1 of
Cardiac transplantation recipients with cardiac valvulopathy present. Murmur of MR and uncommonly, tha
Dlsordora of Cordlovaacular System
,.--------~------~~___;;;~.;_~~;.:.::~~!!::;..:.:.._------~~~
I 443 •
-
"-~~Tl
-""'-b~I• ~e.20: Correctable oau111 of titt ventrloular dyafunctlon In c~lldren
condition C/uos fo diagnosis
i. congenltal cardlovaacutar dleoaaea
Anomalous left coronmy artery from
ECG changes ol myocardial Infarction In I, aVL, V4-6; 20. Doppler
pulmonary artery echocarcJlo,Jraphy
severe coarctatlon ol aorta Woak fomoral pulses; echocardlography
Critical aortic stonosls Auscultation; echocardlography
Acquired cardiovascular dlaoaaea
1
. . .
Takayasu arterltls Asymmetric pulses, bruit, Doppler, sclntlgraphy, angiography
Tachyarrhythmla Disproportionate tachycardia
Ectopic atrial tachycardia ECG
Permanent junctlonal re-entrant tachycardia Esophageal electrophyslology
Chronic atrial flutter
Severe hypertension Blood pressure; fundus examination
~ Metabolic and nutrltlonal causes
Hypocalcemla Setting (newborns; severe hypoparathyroidism); Chvostek, Trousseau signs;
prolonged QTc on ECG
Infantile berl-berl Prominent edema, diarrhea and vomiting; documented thiamine deficiency in
mother (if breastfed)
Carnltlne deficiency Hypoglycemia, congestive heart failure; coma; ventricular hypertrophy; high
ammonia, low carnltine
Hypophosphatemla Poorly controlled diabetes; following hyperalimentation, nutritional recovery
syndrome; recovery from severe burns; hyperparathyroidism; vitamin D
deficiency; hypomagnesemla, Fanconi syndrome; malabsorption
Selenium deficiency Kashan disease (endemic in parts of China); chronic parenteral nutrition, AIDS
tricuspid regurgitation, may be present. The patients are Anomalous Left Coronary Artery
prone to embolic phenomena. The electrocardiogram from Pulmonary Artery (ALCAPAJ
shows non-specific ST and T changes with or without left ALCAPA should be considered in a patient with heart
ventricular hypertrophy, conduction disturbances, failure with or without a murmur suggesting MR and a
arrhythmias or pseudo-infarction pattern. Chest X-.ray pattern on electrocardiogram that suggests anterolateral
shows cardiomegaly with pulmonary venous .hypertens1?n. myocardial infarction (Fig. 16.45). Echocardiography
Echocardiogram confirms dilated ventricular cavity shows a large right coronary artery and absence of the
without hypertrophy of the left ventricle or the septum; origin of left coronary artery from the aorta. The left
left ventricular contractility is reduced. coronary artery is seen to arise from the pulmonary artery
Treatment consists of decongestive therapy with and shows flow in the reverse direction in the left anterior
vasodilators, especially ACE inhibitors. B~ta-~lockers descending artery and the left circumflex artery. This flow
control the heart rate and reduce catecholamme-mdu~ed reversal results from collateral flow into the left coronary
vasoconstriction. Carvedilol, a beta-blocker with system from the right coronary artery. Angiography is
peripheral vasodilator effect, is us~ful i~ managen:ient of rarely necessary for the diagnosis. The treatment is
CCF, especially in patients with disproportionate surgical and requires mobilization and tr'1nslocating the
tachycardia. The starting dose is 0.1 mg/kg/day once origin from pulmonary artery to aorta.
daily, which is gradually increased to 0.5 mgl_kg~d.ay.
.
G ra d ua l improv ement occurs in a .s1gnif1cantt Restrictive Cardiomyopathy {RCMJ
proportion. The prognosis for individual patients canno
It is relatively uncommon in childr~n. Rest.ricti~n to
be predicted and treatment should continue for prol~nged
.
.
periods.
.
. t h erapy, about one-third
Despite aggressive
h
chddren with card10myopat Ycon mue
t·
.
to deteriorate an
kl
eventually become refractory. Intermi'tten t (wee y or f 1-
of
d
b'
ventricular filling is u sually ass?et~ted with .e1t~er
endomyocardial fibrosis or endocardtal fibroelastosis ~vtth
a normal or small er than normal left ventr~cl~.
m
. d · fusions are use u 1 Endomyocardial fibrosis was previ?usl~ ~ndem1~ m f
weekly) dobutamine or levosimen an m f b but is now rare. There is dense f1brosIS m the apical
. . . t t be aware o a num er Kerala
< CI • 1 P illary
in some patients. It is importan o ' ' . th •
and inflow regions of U1e left and right ventric es. ap '.
of correctable conditions that can mimic cardiob~~op~ Y muscles and chordae may be tethe~ed b~ the co~ec~ve
(Table 16.24). Clues to these conditions a;~ 0 a~) on
clinical and laboratory findings, or ECG ( ig. · · 16 tissue, resulting in severe mitral or tncuspid regurgitation.
• 444 I ~--------------------..!!!•!•o~n~tL_~n~IP~a~d~ln~tr~lc~•--------------~~~~-----~
· I r ti· 1
1 r... ·,-I ,-1 f. , ·1Jl r •
I !.
1
,. I 1 •l I •i-. I : - j '
: . ! .•
I
. .-
1
.I ! I I I 1· j : J._l -
! i I ·1 .I • . - r-
I 1
1 I
I .i
m !I
I
t
.1.
. .J . -f
·.-i···
I I
- !_ _ . _ _ _
Fig. 16.44: Pompa disease with blventrlcular hypertrophy. Note the characteristically tall QRS voltage s, and T wave inversion
...
Disorders of Cardiovascular System
I 445 -
'"'--*'" •
- 446 I ~--------~~~~------~E~s~se~n~t~la~l~P~ed~l~a~tr~lc~s--------------~~~~~----~
. adolescents. Systemic hypertension is rar
shows iln echo-free spnc<.! behind the posterior left children andd ung children, but when present Usuaue
vcntriculnr wnll. Evide nce of rl~hl ntrial or right in infants an yo · ( dary hyp t · Y
due to an underlying di.Sease secon . . er ens1on).
vcntriculnt· din~tolic collnp!1c indicates n hemodynnmically f essential hypertension increases wjn.
significant effusion. PcricnrdiocuntcsiH is done to The preva Ience O
~'
. ately 3-4% of chi·1d ren an d a d olescents
determine the etiology i1nd relieve cnrdlnc tnmponade, if age. Ahpprotximsion and 10% have elevated blood pressure
present. Treatment will depend on the etiology. Surgical have yper en .
drninage is indknted, If pyopcricardium is suspected.
Etiology
Chronic Constrictive Perlcardltls . gy of essential hypertension is rnultifactorial.
Th e e tio1o . t· f
Constrictive pericarditis is not uncommon In our country, Ob es1'ty, insulin resistance,. activa
d"
ton o sympathetic
h t .
following tuberculous infection and less commonly, nervous system, disorders m so mm omeos as1s and
following pyogcnic pericarditis. Fibrous thickening of · -angiotensin system, vascular smooth muscle
renm 'd 1 l . f
both layers of the pericardium encases the heart and structure and reactivity, uric act ~ve s,_ genetic actors
restricts filling of both the ventricles equally; calcification and fetal programming ha~e b.een 1mphcated. There is
is rare in childhood. The myocardium is not involved often a history of hypertension m the parents.
initially, but the fibrous process may infiltrate the myo- Approximately 90% of secondary hypertension in
cardium. Dyspnea, fatigue and progressive enlargement children are due to renal or renovascular abnormalities.
of the abdomen are common. The major renal causes are chronic glom:rulonephritis,
Jugular venous pressure is always elevated with equally reflux or obstructive nephropathy, polycystic or dysplastic
prominent 'a' and 'v' waves and a prominent 'y' descent. renal diseases and renovascular hypertension. Coarctation
lnspiratory filling of neck veins (Kussmaul sign) is seen of the aorta and Takayasu arteritis are leading vascular
in about one-half. Liver is enlarged and pulsatile; ascites causes. Hyperthyroidism, hyperparathyroidism, congenital
with unilateral or bilateral pleural effusion is common. adrenal hyperplasia, Cushing syndrome, primary
Splenomegaly mny also be present. Pulse is fast and of aldosteronism, pheochromocytoma and neuroblastoma
low volume and pulsus paradoxus may be present. The are uncommon.
precordium is quiet with a normal-sized heart. First and Transient or intermittent hypertension may be caused
second sounds are normal. An early third heart sound by postinfectious glomerulonephritis, rapidly progressive
(pericardial knock) is commonly hee1rd. The EKG shows (crescentic) glomerulonephritis, Henoch-Schonlein purpura.
low voltage in 75% pa ti en ts and non-specific ST-T changes hemolytic uremic syndrome, acute tubular necrosis, and
in all cases. Normal electroc<1rdiogram is against the diag- renal trauma. Raised intracranial pressure, Guillain-Barn
nosis of constrictive pericard itis. Occasionally, there is right syndrome, burns, Stevens-Johnson syndrome, porphyria,
axis deviation or right ventricular hypertrophy pattern. poliomyelitis, encephalitis, drugs (e.g. sympathomirnetic
The chest X-ray shows normal-sized heart with ragged agents, steroids, cyclosporine), heavy metal poisoning
or shaggy borders and prominent superior vena cava (e.g. lead, mercury) and vitamin D intoxication nuv result
merging with the right atrial margin. The lungs may show in acute elevation of blood pressure. ·
pleural effusion and plate atelectasis. Hemodynamic
studies reveal elevation of right atrial mean pressure, right Definition and Staging
ventricular end-diastolic pressure, pulmonary artery The American Academy of Pediatrics (AAP) clinical
diastolic pressure and the pulmonary artery wedge practice guidelines for screening and management of high
pressures, which are identical. The right ventricular end-
blo?d pressure ~ children and adolescents (2017) prodde
diastolic pressure is more than one-third of the systolic
revised normative data on distribution of blood oressure
pressure. The cardiac index may be normal or reduced,
in normal weight children. H ypertension is d~fined as
but the stroke volume is low. In some cases, therapy with
average systolic blood pressure (SBP) and/ or di,1stolic
digitalis may improve the hemodynamics indicating
blood pressure (DBP) that is 95th percentile for ~·we. sex
presence of myocardial dysfunction.
and height on three different occasions. Elevated,:,blood
Surgical decortication of the pericardium results in
pressure is defined as SBP or DBP that are 90th percentile
normalization of the hemodynamic abnormalities in most
but <95th percentile. Adolescents with blood pressure
cases. Some cases of long-standing constrictive pericarditis
betwe~n 120/80 and 129 / <80 mm Hg are also consider~
with myocardial dysfunction may improve slowly or have as l~avmg elevated blood pressure while hypertension is
residual myocardial dysfunction. A full course of defmed by blood pressure >130/80 mm Hg in this age
• antitubercular treatment often follows pericardiectomy if group. Children w ith blood pressure between the 95th
• the cause is not clear. percentile and 95th plus 12 mm Hg are classified as stage
SYSTEMIC HYPERTENSION
I hypertension and children with blood pressure above
95th plus 12 mm Hg have sta ge n hypertensioll·
Essential (primary) hypertension, the most common form Figures 16.46 and 16.47 indicate blood pressure cut off ~or
of hypertension in adults, is increasingly recognized in stage I and stage II hypertension in girls and boys with
Disorders of Cardiovascular System
. .,
- - ---· -----------
----
-- - - - - --
- - - - - -·- - - - - - - - - - - - -
--- -~-
100 - -
-~--
·t --
.....::=-'.T-_-__- -_-_-_ -_-_- -_-_- -- -- --
-J-- - 1 - -- - - ·-· - -
===-_-_-__
- -- -
-_-_-_
-
-_
-_---
\ ··.
-- - - -- - - - - -
- -
- -- -
- -
- -
- - - - - - - -- - - - - - - - - -- --
- - - -- - - - - - - - - - - - - - - - - - -- - - - - -- -- - - - - - -
90 -- -- - - --- ------ - - - - -- - - - -- - ·-
-·- - - -- __ - - --- - - -- -- - - --
"
0 3 . 4' 5 6 7 8 9 10 11 .. , 12 13 14.-· 1s ' 1s ·:' _11 · - 1a
. .
+ ,.
'·,~ . . . .... .:
9oth DBP ~ 95thDBP -l:r- 95th+1 2_ mm Hg DB P, .
.... i ,,. '·
\ ~
'.
. t;.
.-
·-,··
• .,,...
,":
.. ........
IW .·
~ j - - -- •• ---
.,,
I
"f
Fig. 16.46: Blood pressure levels for boys at 50th percentile for height. Chart depicting 90th (c losed diamonds). 95th (open
squares) a nd 95th + 12 m m Hg (o pen triangles) percentile values for (a) systolic and (b) diastolic blood pressures. representing cut
Off values for the d iagnosis of elevated blood pressure and stage I and stage II hypertension. respec tively, In boys (Based on
Arnerlcan Academy of Pediatrics clinical practice guidelines for screening and management of high blood pressure In children
and adolescents, 201 7)
• 44a I Essential Pediatrics
1- - t - -r - - 1- - -1-- --1- -
- - -- - - -f------ - - - -- - 1-- - 1 - -- 1- - _ _ ,_ _ _ - - -- - - -
- - - - -- - - -i - -1 - - 1- --1- - - - - - t- - + - -- 1---i-- -
- - -- - -- - - - - l-- - + - -- 1- - --~--l---i-----1--
14vcrt--r---r--t---+--+--1---+--~~--1---1-----1---l---+---t---t---t--T----t
--~--I---+--~-- - - •-- - + - -- •-- ~
-- ----1----l---=j~~=5·t;!·:::t==i
- - -- - - - - - - -- -- - - - - - - -
13v == ======---- - --- == ==1- - /---.l.·~~~+--_
---l_ -_-r===+-_-_-_-;~---r-_-_-_--=-1 ~r-
--l---1---l----J_,,---
=- =---i---1---1---l---~--1--
--~--1----I-- ~ ·- ,,,__ -~
- 1- - - -1 - --1- ---t T --1 i
1- --1- - 1-- - - - --l - - 1 -- I ~T __ '-- ~ ·-
120 ~ ~r ,._ - - - - ---1--- ,,,,i-._,..,.I""' -
~ 7_ - ~
~1~-
_- --=!·--'---l---l--l----Jl----l-- ~~~1--1---1---1--+-----I
i'r - - ----::::;;;;t /
--1---- 1-----l-- -J~ --~r--"-+--l---+--+-~--
110 - l - - - - l ---1· ~..... ~l---if--1
- - - ---- - - - - - -
- ~ I _____.-
90i--J--t-----i~-t--+--+--+--~--l--l---+----+---l--+---1--~---1----l
- - - - - -- - - - - - - -- -- - - - ·- - -l- - -+ - - l- --1--- -1--- -
,_ - - ---- - - ------ --- - - - --1 -- -1- - 1 -- 1 -- 1 - - - l f -- I- -
>- - - -- - - - - - - - ----- - __ _,__ _,___ ,_ _ - - -- - ---
------ - - - - - - - - - - - - - - -1--- -<- - - 1- -
80
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
a
-+- 90th DBP -o- 95th DBP -f:r. 95th+12 mm Hg DBP
ioo--i=:=::::r==r=:::=r:=:::r---i--r-.----,--r---r-~--.--.----,r----r--r--.,.......-__,
- --- - --- - _ _ -_ _ 1-_-----='==-=-- r--- r - - i -- \ -- ji -- 1- --ll- - l_ _J_ _ j
-- - - - - - - - - -- - - -- - - - - -i---- --1-- -1- - - - -- - 1 - - -1-- - 1
- - - - - - ·- - - - - - - - -- --
go-EEF=FFFFF~~~~·-*~~~±~±3 ~--"-"'·- - - 1- -- -- - - -- - - ·- - --
1--,.L=-D--"'Y=-
:.._~= -
--
- - - - - - - - - - 1- -+----l--- - l-- - I
40 .JY- ~.--
~ -- ~~~ ~- - - --
. ~ ~~~ ~ ~ - -- ~~~~ ~~~~~
.60 ~v-
-
---t-
---=-~=~::-+- - 1 -=---=---=-+-=-==-i----::----::--:=+i---::--~=-i
--=---t-----:-+
0 1 . 2 ' 3 4 5 6 7 8 9 10 . 11 12 13 - 14 15 16 17 18
. L
Gins
Age
SPB
1
98
2
101
3 4
Disorders of Cardiovascular System
>13
-
102 103 104 105 106 107 108 109 111 114 120
DBP 54 58 60 62 64 67 69 71
68 72 74 75 80
Boys SBP 98 100 101 102 103 105 107
106 107 108 110 113 120
DBP 52 55 58 60 63 66 69 70 72
68 74 75 80
stature at median for age. Simplified tables, which can be activities, including sleep. ABPM is more accurate in
used in office practice, to define patients who need making a diagnosis of hypertension, and its parameters
evaluation are available (Table 16.22). Blood pressure cut- correlate more strongly with end orange damage, than
offs identifying children in the outpatient who need casual blood pressure. ABPM is recommended in children
further evaluation are provided in Table 16.22. with high risk of hypertension {chronic kidney disease,
diabetes mellitus, obstructive sleep apnea, preterm
Measurement of Blood Pressure
children and children with obesity), where clinic blood
Blood pressure can be measured by auscultation, pressure might be normal but ambulatory blood pressure
palpation, oscillometry and Doppler ultrasound. While is high (masked hypertension) or vice-versa (white coat
oscillometric devices are readily available and easy to use, hypertension).
they are susceptible to artifacts and require calibration.
Hence, the auscultatory method preferred for confirming Clinical Features
the diagnosis of hypertension. Blood pressure should be
Hypertension in children is usually asymptomatic unless
measured after a period of adequate rest (3-5 min), twice
blood pressures are high or sustained. Symptoms are
on each occasion in the right arm in seated position. The
common with secondary hypertension. Headache,
stethoscope is placed over the brachia! artery pulse, below
dizziness, irritability, epistaxis, anorexia, visual changes
the bottom edge of the cuff. An appropriate selection of and seizures occur with significant elevations of blood
cuffs is necessary (Table 16.23). Cuffs should have a pressure. Marked increase in blood pressure may result
bladder width of approximately 40% of the arm circum- in cardiac failure, pulmonary edema and renal
ference midway between the olecranon and acromion. The dysfunction. Hypertensive encephalopathy presents with
bladder should cover at least two-thirds of the upper arm vomiting, ataxia, stupor and seizures. Hypertensive crisis
length and 80-100% of its circumference. may present with decreased vision, symptoms of
The cuff is inflated rapidly to occlude the brachia! artery encephalopathy, cranial nerve palsies, cardiac failure and
(at least 20-30 mm Hg above expected SBP). The cuff is rapid worsening of renal function. Eye examination shows
deflated slowly at the rate of 2-3 mm Hg pe~ second w~e papilledema or retinal hemorrhages. Subclinical target
auscultating at the cubital fossa. Systolic pressure is organ injury may occur in asymptomatic children and
indicated by the appearance of Korotkoff sounds (phase include left ventricular hypertrophy, increased carotid
I) and diastolic pressure by its disappearance (phase~). intima media thickness, retinopathy and microalbwninuria.
Ambulatory blood pressure monitoring (ABPM) is a Children with chronic renal disease present with polyuria,
procedure where the child wears a device that records bl~d polydipsia, pallor, weight loss and growth retardation.
pressure at regular intervals (usually every 20-30 mm),
through a 24-hr period while the child performs regular Evalua tion
1 Children with confirmed hypertension need evaluation
j-'7 - Tabfe ·15,23: Recommended dimensions tor ,
blood pressure cuff bladders to identify potential causes, identify comorbidities and
Width (cm) Length (cm) Maximum arm extent of target organ damage. Patients require a detailed
Age group
circumference (cm) history and physical examination. The history should
10 include sleep and treatment history, smoking a~d alcohol
Newborn 4 8
intake, drug abuse and family history (e~rly car~1ovascular
I
Infant 6 12 15
diseases, hypertension, diabetes, dyshp1derrua or renal
Child 9 18 22 diseases). The birth history and grow.th p~t.ter~s are
Small adult 10 24 26 elicited. Examination should focus on idenhhca_h?~ of
Adult 13 30 34 pallor, edema, syndromic facies,_ambiguous or ~mlize~
large adult 16 38 44 genitalia, rickets, goiter, and s_k m chang~s {~afe au la1t f
52 spots neurofibromas, rash, stnae). Examination of eyes
Thigh 20 42 . d ~e for proptosis, extraocular muscle palsies and
. d ch that the largest arm IS o . . . d ne for
Maximum arm circumference IS calculate SU aoo;.0 (Adapted from fundal changes. Detailed exammahon is o l' b
Would still allow bladder to encircle arm by at least asymmetry of peripheral pulses, upper and lower im
Fourth Task Force report)
- 4so I Essential Pediatrics
.
blood pressures, card 1omega Iy, h eart rate, cardiac r h y thm The goal of therapy for children and adolescent~tlh
abnormalities, murmurs and pulmonary edema. hypertension is to reduce bloo? pressure below 90th
Abdominal examination may show hepatomegaly, percentile and <130/80 mm.Hg m adolescent, except in
·
abdominal mass or ep1gastnc · or rena lbrmt. · presence of chronic kidne)' disease, where or target org<'n "
Laboratory evaluation includes estimation of blood damage, when the goal is to reduce blood pre~sure to less
levels of creatinine and electrolytes and urinalysis. Renal than 50 to 75th percentile. Pharmacothernpy
ll · 11s done
1 in a
ultrasound may identify a mass, scars, congenital stepped-care approach andf usua bl d y starts wit la ow
t 1 dose
anomalies or disparate renal size. The evaluation of of a single agent (step l}. 1 00 pressure con r_o is not
achieved the dose is titrated 4-6 weeks until blood
comorbidities requires fasting lipid profile and glucose pressure ~oals are achieved or the maximum dosage for
levels to identify dyslipidemias, metabolic syndrome and the drug is reached (step 2). If adequate blood pressure
diabetes mellitus. Children with history of sleep- control is not achieved with a single agent, a second agent
disordered breathing may benefit from polysomnography. with a complementary mechanism of action should be
An echocardiogram is used to identify left ventricular added and dose titrated until adequate control or dosage
hypertrophy and screen for coarctation of aorta. Children limit is reached (step 3). If adequate blood pressure control
with suspected renovascular hypertension are is not achieved with a two-drug regime, a third agent from
investigated by Doppler studies or angiography. a different drug class should be added (step 4).
Investigations like plasma renin and aldosterone, plasma/ In the case of hypertensive emergencies, the safest way
urine steroid levels and plasma/urine catecholamines are
rarely required. is to lower blood pressure up to -95th percentile by using
a medication that is administered by continuous
Treatment intravenous infusion in an intensive care unit. In general,
the pressure should be reduced by up to 25% over the
The treatment of hypertension in children and adolescents first 8 hours (10% in the first hour), followed by remainder
has two components, therapeutic lifestyle interventions and planed reduction over next 12-24 hours. Too rapid a
pharmacotherapy. Weight reduction, increased physical reduction in blood pressure may lead to cerebral ischemia.
activity and dietary interventions are the major therapeutic Drug choices include labetalol, nicardipine and sodium
lifestyle interventions. Weight reduction in overweight nitroprusside. Nicardipine is preferred in children due to
children results in significant reduction of blood pressure, its efficacy and safety, but is not easily available
and decreases other cardiovascular risk factors like (Table 16.25). Many patients in hypertensive crisis are
dyslipidemia and insulin resistance. Current physical volume depleted because of a combination of decreased
activity recommendations for children include 30 to 60 oral intake and pressure natriuresis. Volume repletion in
minutes per day at least 3 to 5 days per week or more of such conditions will help restore tissue perfusion rmd
moderate intensity aerobic exercise plus limitation of prevent a precipitous fall in blood pressure that may occur
sedentary activity to less than 2 hours per day. Children with intravenous antihypertensive therapy.
with hypertension may benefit from a dietary approach to
stop hypertension (DASH) diet which incorporates Prevention
increased intake of fresh fruits and vegetables, fiber, non- Prevention of high blood pressure in children can be
fat dairy and whole grain as well as a reduction in sugar achieved by preventing childhood obesity. Regular
and salt consumption. The recommendation for adequate physical activity, consumption of fruits and vegetables,
sodium intake is 1.2 g/ day for children 4 to 8 years old and moderate salt intake and limited consumption of
1.5 g/ day for older children. processed food items and animal fats, and reducing
Children with symptomatic essential hypertension, sedentary activities will aid in lowering the prevalence of
hypertension associated with chronic kidney disease, high blood pressure in children.
diabetes-associated hypertension, evidence of target-organ
damage (left ventricular hypertrophy), or failed non- Suggested Reading
pharmacologic interventions require pharmacologic • National High Blood Pressure Education Program Working Group
therapy. Agents approved for management of hypertension on High Blood pressure in Children and Adolescents. The fourth
report on the diagnosis, evaluation and treatment of high blood
include angiotensin-converting enzyme (ACE) inhibitors, pressure in children and adolescents. Pediatrics. 2004;114(2 Suppl
angiotensin receptor blockers (ARB), beta blockers, 4th Report): 555-76. .
c.alcium channel blockers and diuretics (Table 16.24). ACE • Raj M, Sundaram KR, Paul M, Deepa AS, Kumar RK.,Obcsity in
I
children - time trends and relationship with hypertension, Natl
inhibitors, calcium-channel blockers and thiazide diuretics Med J India, 2007;20:288-93.
should be used as first-line drugs in children_. ACE
inhibitors or ARB are preferred in patients with diabetes
PULMONARY ARTERIAL HYPERTENSION
or chronic kidney disease, however, these agents sho~Id
be used carefully in girls of childbearing age due to nsk Pulmonary ~rterial hypertension (P AH) is defined as
of jnjury to the developing fetus. resting mean pulmonary arterial pressure greater than
Disorders of Cardiovascular System 1451 -
Tabla 16.24: Dosage of common antihypertensive medfcatlons tor'outpatlent managemen1
Agents Dose; frequency Comments
'. ACE Inhibitors, anglotensln receptor blockers
captopril 0.3-6 mg/kg/day; tid Use cautiously If GFR <30 mUmin/1 .73 m2 ; avoid in renal aMry
Enalapril 0.1-0.6 mg/kg/day; qd or bid stenosis
Lisinopril 0.06-Q.6 mg/kg/day; qd Use smaller doses in neonates
Ramipril 6 mg!m2; qd Monitor serum potassium, creatinine regularly
lrbesartan 4-5 mg/kg/day Hyperkalemia, impaired renal functions; anemia,
Losartan 0.7-1.4 mg/kg/day; qd neutropenia, dry cough infrequent
Calcium channel blockers
Amlodepine O.OS-0.5 mg/kg/day; qd-bid Extended release nifedepine must be swallowed whole
· Nifedipine (extended 0.25-3 mg/kg/day; qd-bid release) Side effects: Headache, flushing, dizziness, tachycardia; lower
lsradipine 0.15-0.8 mg/kg/day; tid extremity edema, erythema
. Beta-blockers
Atenolol 0.5-2 mg/kg/day; qd or bid Decrease dose by 50% at GFR <50 mUmin/1 .73 m2; give on alternate
Metoprolol 1-6 mg/kg/day; bid days at GFR <1 o mUmin/1.73 m2 ; sleep disturbances with
Labetalol 10-40 mg/kg/day; bid or tid propranolol, metoprolol; hyperlipidemia; avoid in asthma, heart
failure; blunt symptoms of hypoglycemia
Alpha agonlsts
Clonidine 5-25 µg/kg/day; tid or qid Abrupt cessation may cause rebound hypertension; sedation
Prazosin 0.05-0.5 mg/kg/day; bid or tid May cause 'first dose' hypotension, syncope
Vasodilators
Hydralazine 1-8 mg/kg/day; qid Hypertension refractory to other drugs;
Minoxidil 0.1-1 mg/kg/day; qd or bid Side effects: Headache, palpitation, fluid retention, congestive heart
failure; pericardia! effusions and hypertrichosis with minoxidil
Diuretics
Furosemide 0.5-6 mg/kg/day; qd or bid Monitor electrolytes, fluid status periodically
Spironolactone* 1-3 mg/kg/day; qd or bid Thiazides: Dyslipidemia, hyperglycemia, hyperuricemia, hypokalemia,
Metolazone 0.2-0.4 mg/kg/day; qd hypomagnesemia
. Hydrochlorothiazide 1- 3 mg/kg/day; qd Loop diuretics: Metabolic alkalosis, hypokalemia, hypercalciuria
Amiloride* 0.4-0.6 mg/kg/day; qd *Use cautiously with ACEI, angiotensin receptor blockers
qd: Once daily; bid: Twice daily; tid: Thrice daily; qid:Four times qd
In some situations, it may be possible to affect a complete childhood dilnted cordiomyopolhy, cspccin lly If lhc lm1rt
cure. rntc is relotivcly fixed.
Cllnlcal Features U11dcrlyi11g co11ditio11s: /\ numbl•r of rnngcnlt,11 n ncl
acquirL'd hc.1rt diseases and ccrt.1i11 sr1t•111k conditions
Irregular li~art ra~e: The commonest cause of an irregular
arc known lo be ossociated with cardi nc Mrhythmi.1~
heart r~te is phys1?logical sinus arrhythmia. This can be
(Tobie 16.28). Ventricular and suprnvc•ntricu l.u ,urylhm ias
recognized by a.n mcr~ase. in heart rate with inspiration
con follow cardioc s urgery for rnrn•ction of Cl ID .
and d~crease w~th. expiration. Sinus arrhythmia is usual
following a feb~1le 1~lness ~nd by drugs that increase vagal Operations resulting in scar form .1lio11 in the right
tone (suc~.as d1goxm). It is readily abolished by exercise. ventricle, such as repair of tclralogy of Fi11lot, .ire known
Irregularities ?f rhythm are commonly seen in premature to be associated with ventricular ti1chycarclia. Tlw Fontan
infants especially bradycardia associated with periodic operation for single ventricle physiolo~y or the Senning
ap.nea. c .ommon c~uses of heart rate irregularity in or Mustard procedure for lrnnsposition is known to res ult
children mclude atrial and ventricular premature beats in a particularly high incidence of rc· cn trnnt a trial
and conduction disturbances (Table 16.27). arrhythmias. Orgnnophosphate exposure, tricyclic anti-
depressant overdose, digoxin toxicity, antiarrhythmic
I11appropriate l1eart r~t~: A heart rate that is inappropriately
fast or slow for the clrmcal condition or physiological state drug trea tment and substance abuse e<Hl be a ssoci<lted
should aro~se the suspicion of an underlying arrhythmia. with a variety of arrhythmias.
~ap~ropnately slow heart rate in a child with fatigue, Sy11cope: The commonest rnuse of syncope in children is
g1ddmess or syncope should arouse the suspicion of mediated via the autonomic nervous system, known .1s
complete heart block. Inappropriately fast rates suggest the neurocardiogenic syncope or vnsovngal syncope. A
tachyarrhythmias such as SVT. fraction of syncopa l ep isodes result from cC1rdinc
Unexplained heart failure: Incessant arrhythmias such as arrhythmias. Life-threatening ventricular tilchycMd ia (VI),
as associated with Jong QT syndrome charncteristically
ectopic atrial tachycardia (EAT), permanent junctional re-
results in syncope. It is important to diffe re ntia te them
entrant tachycardia (PJRT) and some forms of ventricular
from vasovagal episodes. Vasovagal syncope occurs in
tachycardia can present as heart failure. At the time of
specific s ituations like prolonged s t<tnding in " hot
initial evaluation, the heart rates may not be inappropriate
environment, sight of blood, painful s timulus, emotion<tl
for the degree of heart failure. Diagnosis may be missed
stress or following a recent illness. Syncopes sccondarv
and requires a high index of suspicion. These conditions
to arrhythmia are sudden, unpredictnblc, paroxysma l and
should be considered in the differential diagnosis of
~ •• :.J # -
usually have no predisposing cause or premonition.
• · Table 16.2~: <;;linical f_e a_tures in arrhythmias Duration of syncope depends upon the dur<ttion of
Irregular heart beat
Heart rate that is inappropriate for the clinical condition . Table 16.28: Arrhythmias suggestive of
1 specific congenital heart disease
Unexplained heart failure
Sick sinus syndrome
Syncope, palpitations, chest discomfort Sinus venosus, atrioventricular canal defect, Holt Oram
Underlying cardiac anomaly known to be associated with syndrome with atrial septal defect (ASD)
rhythm disorders Narrow ORS tachycardias
Family history of sudden cardiac events Ebstein anomaly; corrected transposition with Ebstein
..
i ' Table 16.27: Causes of irregular heart beat
anomaly
Atrioventricular canal defect, ASD, pulmonic stenosis, total
.Sinus arrhythmia anomalous pulmonary venous connection, tricuspid atresia
.Other common and usually benign causes Atrial fibrillation and flutter
Congenital mitral stenosis, total anomalous pulmonary
Supraventricular (atrial and junctional) premature beats venous connection, coronary AV fistula
Ventricular premature beats WPW and pre-excitation syndromes
Transient conduction disturbances (Wenckebach type), Ebstein anomaly; corrected transpos ition with Ebstein
atrloventricular and sinoatrial blocks anomaly
Transient bradycardia in a premature infant
Wide ORS tachycardias
Uncommon but potentially serious causes Anomalous left coronary artery from pulmonary artery,
Mobit:z type II heart block coronary AV fistula, arrhythmogenic right ventricle, atrio-
Ectopic atrial tachycardia; multifocal atrial tachycardia ventricular conduction defects, corrected transposition of
Polymorphic ventricular tachycardia and Torsades great arteries; Ebstein anomaly
Atrial fibrillation, with or without WPW syndrome Postoperative patients
Atrial flutter with variable conduction Supraventricular, ventricular arrhythmias
- """' ----------------==~~~==----------~~~----~
"rrhvthm\,,, Somt' form8 nf hm~ t.).'1' My mlr1rn1cs a11u
E11ant101 Pediatric•
b~-~ ..-_-- - ...-. ~---·--- - -Table 16.33: l?ifferential diagnosis of narrow QRS tachycardia
Arrhythmia Pwaves P-QRS relationship Response to adenosine
Sinus tachycardia Normal 1:1 Transient slowing; AV block
: Sinus node-entry Normal Usually 1:1 No effect or transient AV block
·· Ectopic atrial tachycardia Abnormal and different Usually 1:1 No effect or transient AV block
from baseline
Atrial flutter Saw tooth appearance 2:1or1:1 Transient AV block may unmask flutter
rates exceed 240/min waves; rarely arrhy1hmia terminates
~1 Postoperative intra-atrial Slow atrial flutter, P waves Variable, often 1:1 Transient AV block may unmask flutter
re-entry• different from baseline waves; rarely arrhythmia terminates
Multifocal atrial tachycardia Multiform Usually 1:1 No effect or transient AV block
: .Junctional ectopic tachycardia Normal (AV dissociation) Complete AV No effect on rate; transient retrograde VA
or inverted (1 :1 retrograde dissociation is conduction block unmasks AV
conduction) diagnostic dissociation
• _AV nodal tachycardia Usually not visible (masked 1:1 Sudden termination is characteristic
by RS complexes}
AV re-entrant tachycardia
Junctional re-entrant
..tachycardia
Inverted (retrograde VA
conduction)
Inverted (long VA
conduction time~ ,
1:1
1:1
Sudden termination
Fig. 16.49: Six-lead ECG. Adenoslne was administered to a child with regular narrow QRS supraventrlcular tachycardia. Note the
tachycardia terminates with a P wave. Note delta waves with short PR Interval that Is prominently seen In lead I
by n 2:1 P-QRS ratio during n narrow QRS tachycardia Wid£' QRS tnc11ycardi11: Wide QRS complex tachycardias
indicates atrial flutter (Fig. 16.50). Evidence of complete usually result from foci or circuits in the ventricles. Some
AV dissociation (no consistent P-QRS relationship) supraventricular tachycardias can also result in n wide
indicates junctional ectopic tachycardia. QRS configuration. The overall approach is quite similar
Ade11osi11c administration acts by producing a marked to narrow QRS tachycardias, with identification of P
slowing of AV node conduction (Table 16.33). The effect waves, defining P-QRS relationship and determining the
QRS axis configuration (Fig. 16.52).
of adenosine lasts for a few seconds. Side effects are short-
lived and include flushing, chest pain and dyspnea. Demonstrable AV dissociation (inconsistent P-QRS
relation) suggests ventricular tachycardia (VT). ln most
Adenosine needs to be administered rapidly followed by
situations, however, it is not easy to distinguish VT from
rapid push of normal saline as a bolus. The recommended
SVT. If the patient is stable, administration of adenosine
dose is 50-300 pg/kg. Most re-entrant tachycardias, where
will terminate or unmask SVT. If there is no response,
AV node is a part of the circuit (AV node re-entrant
treatment for VT should be initiated. In stable patients, it
tachycardia, AV re-entrant tachycardia), will be terminated is better to initiate pharmacologic treatment of VT before
by adenosine. Atrial flutter is seldom terminated by considering cardioversion since the response to initial
adenosine. The transient AV block that results from treatment can help decides long-term therapy. LignocaiJ'le
adenosine administration can unmask flutter waves on is the initial choice; procainamide is an effective
the EKG thereby confirming the diagnosis (Fig. 16.51). alternative; others include amiodarone, sotalol, mexeletine
Similarly transient slowing of AV conduction can unmask and flecanide.
ectopic atrial tachycardia. If adenosine is not available,
I vagal maneuvres can be attempted. For infants and young Unstable wide QRS tnc/1ycnrdin: Wide QRS tachycardia
children, an ice filled plastic bag placed on the face is the with hemodynamic instability is a medical emergency.
most effective vagal maneuver. Older children can be Synchronized cardioversion (0.5-2 J/kg) should be
performed immediately. For pulseless patients, CPR
encouraged to perform the Valsalva maneuver or carotid
should be initiated. Subsequent treatment should folloW
sinus massage can be attempted. Eyeball pressure is
contraindicated in infants. standard guidelines recommended for pulseless patients
with VT (Fig. 16.53).
Disorders of Cardiovascular System 1 457 -
· . 1 l l "J_j·l· ! ~ · · ·1 :•!.
. ' - .. . ..
1 ! : , ,1
• • - • ' - • - • .
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I . • I ·-·-·-~----·-·- --· ·
...:...O... •..L-!...._ l ......J. -~-. ~ -....__.... __ _ :_____ __ _ - - · -· - - -
Fig. 16.50: Atrial flutter: Regular narrow QRS tachycardia at a heart rate of 150/min. Heart rate was fixed at 150/min for several
hours that was suggestive of underlying arrhythmia. P waves were abnormally broad and tall
l · IJ Jll '!J t (~
~ .. t ·
" ' ' ' I I 1 ( - f
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i l ~,,, 1i-,. "~ 1•r.,1\J f'\~t\. "·\.l':it. ,,..,.1,, tA I,,.. '"'r·~ 1 1 1~h1 ~"',. _-t-L ~.
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1.11 '·i
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I ~I 1 I I I I I~ -
\r\ ·'
1 f w "' / I"' i\ " "( I • i
1 !,· 111 I I I . Ii l 1T
I l I f; I I
....Ti 1 ! .11 I I I
I
I Iii T
_tlT 11 I : 1 I . : : _µ+:~~
~ f-x+IJ-11"'11-lll ~ll-rt AI. J..,' tt'~
1
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=t~ i . I I I I I I I I· I : ! !!~ ! I I I
Fig, 16.51 : Response to adenosine administration to 0 child With atrial flutter. Note the unmasking of flutter waves that ore prominently
~n In lead II and Ill. P rate was 300/mfn. Before a~mlnlstratlon Of adenoslne. there was 2:1 AV conduction. The blocked p waves
t0ere hidden within the QRS complexes. After administration of adenoslne. AV block Increased and AV conduction block Increased
4:1 unmasl<lng the flutter waves
- 4se I
PREVENTING ADULT CARDIOVASCULAR DISEASE --._
. ns
M aior · k factors for cardiovascular
. . .in adulthood
disease
.
are cigarette smoking, p~ys1ca 1 1~ac t.1v.~y, ?besity,
Intra-cardiac
1
hypertension, diabetes melhtus and ys 1p1 em1a. Sorne
~
of these risk factors begin in childhood and are amenable
to modification, contributing to primary prevention of
a a a a a a a cardiovascular disease.
Intra-cardiac
Obesity: Obesity influences major cardio~ascular risk
factors such as dyslipidemia, hypertension, glucose
intolerance and inflammation. Emerging cardiovascular
Surface risk factors like carotid intima media thickness as well as
carotid elasticity has also shown strong association with
Fig. 16.52: Wide QRS tachycardia resulting from a re-entrant
circuit Involving an accessory pathway in a patient with right
childhood obesity. Childhood obesity is managed by a
bundle branch block. Surface ECG. can be mistaken for combination of increased physical activity and dietary
ventricular tachycardia. ECG of the top two rows has been interventions.
obtained directly from the atrium using postoperative atrial wires
as electrodes. The bottom strip is the surface ECG from a Hypertension: Primary or essential hypertension is the
monitoring lead. Conversion to sinus rhythm after adenosine is most common form of hypertension in older children and
seen In the last four complexes on the right. a artial contraction, adolescents. Childhood obesity is associated with
Pp wave hypertension in children, which often tracks into adulthood.
Dyslipidernia: Screening for dyslipidemia is recommended
Wide QRS tachycardia
for children whose parents and/ or grandparents required
coronary artery bypass-surgery or balloon angioplasty
before 55 years, those with family history of myocardial
infarction, angina pectoris, peripheral or cerebrovascular
disease, or sudden death before 55 years, and those whose
parents have dyslipidemia. Youth with dyslipidemia are
treated with a diet low in total and saturated fats and
• If 1:1 P-QRS relation , try adenosine
• If AV dissociation IV lignocaine
cholesterol. The intake of complex carbohydrates is
1 mg/kg or IV amiodarone 45 mglkg increased, whereas that of simple sugars is decreased.
• If no response, DC shock Drug therapy is used in patients with significantly
CPR = Cardiop11/monary res11scitation elevated LDL-cholesterol.
Fig. 16.53: Management of wide QRS tachycardia
Diabetes mellitus: Diabetes mellitus is associated with
cardiovascular complications, which develop early in
Irregular wide QRS tachycardia: Sustained and irregular childhood and adolescence. Endothelial dysfunction seen
wide QRS tachycardia is uncommon and usually suggests in both types of diabetes is recognized to aggravate
a diagnosis of Wolf-Parkinson-White (WPW) syndrome cardiovascular risk in later life. Optimal daily and long-
with atrial fibrillation. In presence of hemodynamic term glycemic control, maintenance of blood pressure and
instability, synchronized cardioversion (1-2 J/kg) is lipid levels in the normal values for age, regular exercise,
indicated. If the patient is stable, procainamide infusion healthy diet and avoidance of smoking are necessary.
may be tried.
Tobacco co11sumptiou: Mechanisms by which smoking
Once the arrhythmia has been managed, recurrences
exerts its detrimental effects on cardiovascular systern
need to be prevented. Most childhood arrhythmias include endothelial dysfunction, increased oxidative
warrant evaluation by a pediatric cardiologist for follow- stress, increased arterial stiffness, alterations in lipoprotein
up care and to plan definitive treatment. An echo- metabolism and induction of prothrombotic state. School-
cardiogram, Holter test (24 hours ambulatory EKG based campaigns to prevent smoking and chewing tobacco
recording) and esophageal electrophysiologic study is are appropriate tools to contain this public health concern·
often r~quired .. Invasive intr~cardiac electrophysiol~gic
Suggested Reading
1. Raj M. Obesity and cardiovascular risk in childrl"ll and adolcsa-nts. 2. P.aj M, Sundaram Y..R, Paul M. et al 0--..esity inc.~~..: tt=..e ~
Indian] Endocrinol Metab 2012; 16:13-19. and rdaticnsrup-;.ith hy~~ ~~ ~.!ed Jl::rl2 zm; ~s.
17 Disorders of Kidney and
Urinary Tract
Arvind Bagga • Aditi Sinha • RN Srivastava
RENAL ANATOMY AND PHYSIOLOGY (Fig. 17.1). Six to eight distal tubules join to form the
collecting ducts that finally enter the renal pelvis.
Each kidney is composed of approximately a million
nephrons, each consisting of a glomerulus and renal The early part of the distal tubule on its ascent from the
tubule. The glomerulus is made of a tuft of capillaries and medulla to the cortex lies near the glomerulus of the same
a central region of mesangium. The capillaries arise from nephron. The cells of the tubule in contact with U1e afferent
the afferent arteriole and join to form the efferent arteriole. arteriole are denser than the rest and called marnla densa.
The capillary wall consists of fenestrated endothelium, The smooth muscle cells of the afferent arteriole, in this
glomerular basement membrane and foot processes region, contain prominent cytoplasmic granules that are
(podocytes ) of visceral epithelial cells. The basement the site of renin activity. The juxtaglomerular apparatus
membrane is m ade of type IV collagen, laminin and GGA) is composed of afferent and efferent arterioles, the
heparan sulfate proteoglycan. The Bowman space leads macula densa and lacis cells located between these
into the proximal tubule that has an initial convoluted structures. The JGA is involved in systemic blood pressure
portion, then the straight segment, descending and regulation, electrolyte homeostasis and tubuloglomerular
ascending limbs of the loop of Henle and the distal tubule feedback.
Connecting tubule
o;,,,, "'"'"'"'•'
tubule
~-
Proximal convoluted tubule
Na• (50%) Cortical collecting duct
K• (65--70%)
Thick ascending Na• (2-3%)
loop of Henle K•(2-5%)
Proximal straight tubule
Na•(15%)
Na• (20%)
K•(20-25%}
Medullary collecting duct
Na• (7%)
Fig. 17.1: Renal tubular handling of sodium and potassium. The major sites of reabsorptlon are shown. with percentage of tntere'
cation In parenthesis
460
...
Disorders of Kidney and Urinary Tract j461 -
Renal Physiology
tensin mechanism. The renin-angiotensin-aldosterone
Glomerular filtrat1"0 n d epends upon the higher· pressure system, prostaglandins and natriuretic peptides are
in afferent
h arterioles
d h · The fi"ltr ti" b ·
a on arner is· cons ti"tute d involved in sodium handling. Potassium is completely
by t e en ot elium with slit pores, basement membrane reabsorbed in the proximal tubule; the amount seen in
and podocytes of visceral epithelial cells. Filtration of urine depends upon its secretion in the distal tubule.
solutes. depends upon their · molecular size
· shape and Distal tubules and collecting ducts are responsible for
electncal
. . charge · Th e i trate from the 'glomerular
f · 1 urinary acidification, concentration and regulation of
capil_lanes passes from the Bowman capsule into the sodium balance. Exchange of potassium or hydrogen ions
proximal c?nvoluted tubule, loop of Henle, distal tubule for sodium takes place in the distal tubules under the
and collec~g ducts. The filtrate contains all the diffusible regulation of aldosterone. Antidiuretic hormone mediates
and ultrafiltrable
.. substances presen t mp. 1asma. 5ma 11 absorption of water through insertion of 'water channels'
0
qu~hties ~ protein are usually present, but are reabsor- (aquaporins) on the luminal surface of cells in the
bed m prox~al tubule. Bulk of the glomerular filtrate is collecting tubules.
:eabsorbed into ~he peritubular capillaries and only 0.5%
is excreted as unne. Renal Acidification
The kidney helps in regulation of acid-base balance by
Tubular Reabsorption maintaining plasma bicarbonate concentration at 22-26
The p~oximal tubule~ reabsorb about 80% of the glome- rnEq/L. Depending on dietary protein intake, children
rular filtrate. Approximately 65% of sodium is reabsorbed produce about 1-3 mEq/kg/day of nonvolatile acids.
in the proxi~al tubule, through several active transport Filtered bicarbonate is almost completely reabsorbed, 85
systems. Sodm1? transport is dependent on the parallel to 90% in the proximal tubules and the rest in distal tubules
transport of bicarbonate, chloride, amino acids and and collecting ducts. Bicarbonate, consumed in the
glucose. Tubular reabsorption of sodium and other buffering of nonvolatile acids, is regenerated by the renal
permeable solutes is promoted by the phenomenon of excretion of titrable acid and ammonia. Chronic acidosis
solvent drag during transport of water across the tubular augments the production of ammonia and thus
epithelium. Figure 17.l indicates the principal sites of elimination of acid. Figures 17.2 and 17.3 demonstrate the
reabsorption of sodium and potassium. chief mechanisms invo lved in the reabsorption of
The glomerular filtration rate is regulated by tubulo- bicarbonate and excretion of protons in the proximal and
glomerular feedback that depends upon the functional distal tubules, respectively.
integrity of the JGA. Increased delivery of chloride to the The reabsorption of filtered bicarbonate as well as
macula densa results in local activation of renin-angio- excretion of acid is mediated by tubular secretion of hydrogen
3 Na•
...............-- ------------.-~
I
I
I 2 K•
I
.
I
W+O~ I
t I
I
I
.. _Na•
I
I Carbonic
I anhydrase
Carbonict I- - - - - - ~ HCO'i
anhydrase I
I
H 0 + C02 - - - - - - .;... - - - - - - '
2
~K·
a b
c1-~~====----=====:::t~
ions (H+). In the proximal tubule, filtered HCOJ combines size between 12 and 40 weeks, with the renal length
with H+ to fonn H 2C03 that rapidly dissociates to H 20 and increasing from about 1.0 to 2.7 cm. The fetal bladder is
C02 (catalyzed by carbonic anhydrase at the brush border visualized by 10-14 w eeks, and its capacity increases
of the tubular basement membrane) (Fig. 17.2). C02 diffuses steadily to about 50 mL at term. Beyond 16 weeks, the
along its concentration gradient into the tubular cell, amniotic volume is principally dependent on urine
combining with H 20 to generate HCOj that is absorbed by production.
the peritubular capillaries. The proximal tubule reabsorbs
80-90% of the filtered HCOJ; the remainder is reabsorbed Gtomerutar Filtration
distally. In the distal tubule, the secreted H+ ions combine Glomerular filtration begins at 5-9 weeks' gestation,
with the major urinary buffers, sodium hydrogen initiating urine formation. The fetal kidney receives about
phosphate (Na 2 HP04 ) and ammonia (NH3 ) to form 2-4% of cardiac output, which increases in neonates to
Na~P04 and NH4• (measured in urine as titratable acidity 15-18%. Serum creatinine level is high at birth, reflecting
and ammonium ion, respectively) (Fig. 17.3). The distal ma temal values, but falls rapidly to 0.3-0.5 mg/ d L by the
nephron generates and maintains a steep pH gradient end of first week. Most (92%) neonates pass urine within
between the blood and urine, but its capacity to secrete tt• the first 48 hours. The GFR is low at birth (15-20 mL/
ions is small. Thus, even a slight increase in distal HC03 2
min/1.73 m in the first 3 days in term, 10-15 mL/min(
delivery results in increase in urine pH. Extracellular fluid 1.73 m 2 in preterm) but increases to 35-45 mL/min/l.73 nr
volume and potassium balance also regulate H+ secretion at 2 weeks and 75--80 mL/min/1.73 m2 by 2 months.
and HC03 reabsorption.
Tubular Function
Suggested Reading
Tubular function contributes to urine formation aroU!ld
• Bernstein PL, Ellison DH. Diuretics and salt transport along the 14 weeks' gestation. Postnatal tubular m aturation folloW 5
nephron. Semin Nephrol 2011;31 :475-82
• Srivastava RN, Bagga A. Renal anatomy and physiology. In:
a pattern similar to GFR but its maturation is delayed.
Pediatric Nephrology, 5th edn. Jaypee, New Delhi, 2011;1- 19 Infants have reduced sodium and bicarbonate reabsorptio!l
and limited ability for hydrogen ion excretion. The pB of
Development of Structure and Function urine in newborns is high for the degree of acidernia.
The fetal kidneys are lobulated structures that ascend from
Urine Osmololity
the pelvis to their normal position between 6 and 9 weeks
of gestation. These kidneys can be visualized on antenatal The capacity of the kidneys to concentrate or dilute u~e
ultrasound by 12-13 weeks. The kidneys grow steadily in is limited in neonates. An infant can concentrate his UJ1!1e
I
Sodium Urinary sodium excretion Delhi, 2015; 4~5
Plasma renin, aldosterone • Kaplan BS, Pradhan M. Urinalysis interpretation for pediatricians.
·A~H: ~ntidiuretic hormone; GFR: Glomerular filtration rate Pediatr Ann. 2013;42:45-51.
- 466
L R
a b t_~~~~-:::--:--:--:---~~~~-
Time in minutes
Fig. 17 .5: (a) 99mTc-DMSA scintigraphy showing midzonal scars and loss of volume in the right kidney. The. left kidney i~ normal;
(b) Renal dynamic scan with diuretic was performed in a 6-week-old newborn with Isolated left hydrone~hros1s. The excretion. of lt'l.l
tracer on the left side is sluggish and unchanged with administration of diuretic, suggesting an obstructive pattern of excretion, as
seen with pelviureteric junction obstruction
• Schwartz GJ, Munoz A, Michael F, e t al. New equations to estim ate not infrequent. Gross hematuria is rare in acute pyelo-
GFR in children with CKD. J Am Soc Nephrol 2009;20:629-37 nephritis. Conditions that cause persistent microscopic
• Utsch B, Klaus G. Urinalysis in children and adolescent. Dtsch hematuria include idiopathic hypercalciuria, benign
Arztebl Int. 2014;111:617-25.
familial hematuria, Alport syndrome, IgA nephropathy
and membranoproliferative GN.
HEMATURIA
The presence of blood in urine imparts it a color, which Diagnostic Evaluation
includes various shades of deep red, smoky brown, cola- A history of pain in the flank or suprapubic region, d ysuria
color and faint pink. Parents may mistake very concen- and edema should be obtained. Physical examination
trated urine for that containing blood. Microscopic includes assessment of growth and features of acute or
examination of urine will show red blood cells. Reagent- chronic kidney disease such as edema, h ypertension,
coated dipsticks detect free hemoglobin and myoglobin. unexplained pallor, bony abnormalities and abdominal
Red urine may be present in porphyria and following mass. An audiogram and a detailed eye examination may
beetroot ingestion. Urine appears orange-colored after be needed. Figure 17.6 shows an algorithm for evaluation
administration of rifampicin or pyridium. Uric acid and of patients with hematuria.
xanthine crystals may also impart a pink tinge to the nappy. A fresh specimen is examined for red cells, red cell casts
In children, the commonest cause of gross hematuria is and protein. Absence of large number of red cells in bloody
postinfectious GN (Table 17.2). Urinary tract stones are urine suggests hemoglobinuria (intravascular hernolysis)
.
~
Table 17.2: Causes of hematuria
Glomerular Non-glomeru/ar
Postinfectious glomerulonephritis (GN) Hypercalciuria
lgA nephropathy · Renal calculi
Henoch-Schonlein nephritis Urinary tract infection
Membranoproliferative GN Hemorrhagic cystitis
Rapidly progressive GN Trauma, exercise
Cystic renal disease
Interstitial nephritis
Uncommon Uncommon
Lupus nephritis Vascular malformations
Other vasculitides, e.g. microscopic polyanglltis Coagulation disorders
Membranous nephropathy Thrombocytopenia
Familial benign hematuria Nutcracker syndrome
Alport syndrome Renal or bladder malignancy
Disorders of Kidney and Urinary Tract 1467 -
~~
'
Urlno dipstick, microscopy
Urinalysis >5 RSC/high power field
No
---1Plgmenturla, drugs I
~"'"I Non-glomerular
24 hours urine protein and creatlnine Urine spot calcium, creatinine, protein, urate
ASO, antl-DNAse B 24 hours urine calcium, urate, protein, creatinine
ANA, antl-dsDNA, ANCA Urine culture
Blood albumin, cholesterol Spiral CT abdomen
Coagulation screen
Renal Doppler, magnetic resonance venography
Common causes No etiology Identified
Acute, chronic
glomerulonephritis
Evaluate vision, hearing Common causes
Screen parents and siblings Hypercatciuria
Renal calculi
Urinary tract infection
Hydronephrosis
Consider kidney biopsy
Ag. 17.6: Approach to evaluation of a patient with hematurta. The Initial step In evaluation attempts to distinguish glomerular from
nonglomerular causes of hemoturta (see Table 17.3). Estimation of complement C3 is an important screening test for postinfectious
glomerulonephrltis. Patients with persistent glomerular hematurta might require kidney biopsy and/or screening for familial causes. ASO
anttstreptolysln O; ANA antinuclear antibody; anti-dsDNA anti-double-stranded DNA antibody; ANCA antineutrophil cytoplasmic antibody
or myoglobinuria. In glomerular disease, urine shows A plain X-ray film of the abdomen and abdominal
dysmorphic red cells, of different shapes, whereas in ultrasound is done to exclude major renal and urinary tract
bleeding from renal pelvis or the lower urinary tract, the anomalies and calculi. Blood levels of creatinine are
red cells maintain normal morphology (Fig. 17.7 and measured; specialized blood tests depend on the likely
Table 17.3). Presence of significant proteinuria (2+ or clinical etiology. Surgical conditions that cause hematuria
more) and/or red cell casts suggests glomerular disease. can be diagnosed by appropriate imaging. Invasive
Hypercalciuria should be screened by determination of procedures such as cystoscopy are rarely indicated.
urinary calcium to creatinine ratio on one or more random In a significant proportion, isolated microscopic
samples. hematuria spontaneously disappears over a period of
several years. Other family members may have similar
urinary abnormalities. If there is no family history, a renal
biopsy is not urgently indicated and the patient kept under
observation.
Renal Biopsy
Renal biopsy should be done, if hematuria is associated
with persistent or heavy (3+ or more) proteinuria, history
of renal disease in the family or evidence of chronic kidney
disease in the patient, or if renal impairment or hyper-
tension are seen on follow-up. A biopsy is also considered
in children showing persistent microscopic hematuria for
two or more years even in the absence of the above •
Fig. 17.7: Phase contrast microscopy showing dysmorphlc red features. This procedure is necessary to diagnose IgA
cells (arrowhead). Normal red cells are also seen (arrow) nephropathy, Alport syndrome, thin basement membrane
- 468
disease (typically presents as familial benign hematuria) changes. Persistent and heavy proteinuria, especially ii
and chronic GN. The biopsy is evaluated by light, associated with hematuria, should be promptly evaluated.
immunofluorescence and electron microscopy.
Quantltatlon of Protelnurla
Alpert Syndrome
Protein excretion at 100-1000 mg/m2 I day indicates mild
This condition is inherited in an X-linked manner, although to moderate proteinuria; more than that is heavy
autosomal transmission is known. Mutations in the gene (nephrotic range) proteinuria. Accurate quantitative
encoding alpha subunit of collagen IV (COL4A) result in measurements of 24 hours urinary protein are not needed,
persistent microscopic hematuria, moderate proteinuria if semiquantitative tests are done on a concentrated (first
and progressive kidney failure. A significant proportion morning) specimen. Normally, the protein to creatinine
show high frequency sensorineural deafness; ocular defects ratio, in the first morning urine specimen, is below
(lenticonus, cataract, macular changes) are often associated. 0.2 (mg/mg); a ratio of 0.2-2 indicates mild to moderate
Ultrastructural examination of renal biopsy shows variable and >2 heavy proteinuria. The latter usually corresponds
thickness of glomerular basement membrane with lengths to 3+ or 4+ reaction on boiling or dipstick test.
of marked attenuation to areas of lamination. Therapy is Important causes of asymptomatic proteinuria include
supportive, including the use of angiotensin-converting orthostatic proteinuria, chronic glomerular diseases, reflux
enzyme inhibitors. The majority of male patients (X-linked nephropathy, renal hypoplasia and rarely renal tubular
illness; hemizygous mutations in COL4A5 gene) show disorders (Table 17.4). In orthostatic (postural) proteinuria,
progression to end stage kidney disease. The course the
illness in patients with autosomal recessive illness (mutation ~- Table ·17:4~ ·Conditions presenting -;ith -pfoteinuria
in COL4A3 or COL4A4} is also rapid. Glomerular proteinurla
Serologic evidence for streptococcal infection is present enzyme inhibitors carry risk of hyperkalemia. Patients
in most patients with pharyngitis, though antibiotic with hypertensive emergencies need prompt treatment
therapy may blunt this response. ASO titer is increased in with IV nitroprusside or labetalol.
more than 80% patients; anti-DNase Bis elevated in cases Left ventricular failure: Hypertension should be
of streptococcal skin infection. The titers decrease within
controlled and IV frusemide given to induce diuresis,
4-6 weeks. The level of serum C3 is low in 90% patients
leading to improvement in heart failure. If diuresis is not
but normalizes by 8-12 weeks. Persistent low C3 levels
noted, dialysis is initiated. Respiratory support with
indicate other forms of GN.
positive end-expiratory pressure may be needed.
Management Prolonged oliguria: Treatment, as outlined above, should
Patients with mild oliguria and normal blood pressure be continued and levels of blood urea, creatinine and
can be managed at home. Close attention to blood pressure electrolytes monitored. Dialysis is required in children
and dietary intake is essential. Treatment with penicillin with severe renal failure and prolonged oligoanuria, fluid
has no effect on the course of the disease, but may be given, overload and life-threatening electrolyte distu rbances.
if active pharyngitis or pyoderma is present. The principles Occurrence of secondary infections should be avoided.
of management of patients with severe oliguria and acute
kidney injury are discussed later. Outcome and Prognosis
Diet: The intake of sodium, potassium and fluids is A~ute poststreptococcal GN has an excellent prognosis in
restricted until blood levels of creatinine reduce and urine childhood. The symptoms begin to resolve in the first week
output increases. Overhydration may increase the risk of with loss of edema and fall in blood pressure. Gross
hypertension and precipitate left ventricular failure. hematuria and significant proteinuria disappear within
Patients with azotemia require accurate measurement of 2 weeks, although microscopic hematuria and slight
urine output and daily weight, and restriction of fluid prot~inuria ~~y persist for several months. Hypertension
intake to an amount equal to insensible losses and 24 hr subsides withm 2-3 weeks, but rarely may persist for
urine output. se~eral weeks. Pa~ients with acute GN of nonstreptococcal
etiology have vanable and unpredictable outcome. '01e~e
Diuretics: Patients showing modest edema are treated
cases need close follow-up over several years with periodiC
with oral frusemide at a dose of 1-3 mg/kg; the edema
urinalyses and measurements of blood pressure.
disappears with the return of renal function. Therapy with
IV frusemide (2-4 mg/kg) is necessary in patients with Renal biopsy: A biopsy is rarely indicated in those
pulmonary edema. suspected to have poststreptococcal GN except v;hen
Hypertension: Mild hypertension may be controlled by renal function is severely impaired beyond 7-10 days or
restriction of salt and water intake. Effective anti- serum C3 remains depressed beyond 12 weeks. Patient;
with features of a ~ystemic illness (e.g. systemic Jupt1
5
hypertensive agents include amlodepine, nifedipine or
diuretics. Beta-blockers and angiotensin-converting require a kidney biopsy (Table 17.6).
Disorders of Kidney and Urinary Tract I 411 •
crescentlc Glomerulonephrltls
Rapidly progressive GN (RPGN) is defined as an acute
nephritic illness accompanied by rapid loss of renal
function over days to weeks. The histopathological
correlate is the presence of crescents (crescentic GN)
involving 50% or more glomeruli (Fig. 17.9) suggesting
severe glomerular injury. The chief forms of RPGN are:
(i) immune complex crescentic GN (immunofluorescence
showing immunoglobulin and C3 deposits; normal or low
C3), (ii) pauci-immune crescentic GN (related to small
vessel vasculitis; positive antineutrophil cytoplasmic
antibodies; scant immune deposits) and (iii) anti-
glomerular basement membrane GN (with anti-GBM
antibodies; linear IgG deposits). There is satisfactory
clinicopathologic correlation and patients with extensive Fig. 17 .1 O: Henoch-Sch6nlein p urpura in a 6-yeor-o!d g ir1
histological changes have poor outcomes. Renal biopsy admitted with severe abdominal pain. No e purpuric rash a-1er
should be performed in all patients with severe nephritic the lower limbs
features, which do not resolve within 1-2 weeks.
The outcome is related to histological severity and patient may present with nephritic or nephrotic syndrome,
prompt institution of therapy. Satisfactory results have hypertension, azotemia and crescentic GN. Therapy with
been obtained with initial administration of IV and oral a combination of oral/IV corticosteroids and cyclophos-
corticosteroids and IV cyclophosphamide, followed by phamide initially, followed by maintenance steroids and
maintenance irnmunosuppression for 2-3 years. Prompt azathioprine is recommended . Long-term outcome
plasmapheresis is recommended for patients with pauci- depends on the severity of renal manifestations.
irnmune crescentic GN and Goodpasture syndrome.
lmmunoglobulin A Nephropathy
Nephritis in Henoch-Schonlein Purpura Predominant deposition of IgA in the glomeruli, chiefly
Henoch-Schonlein purpura (HSP) is the most common in the mesangium and occasionally in capillary walls is
vasculitis in children (Fig. 17.10). Mild renal involvement characteristic . The usual clinical manifestation is
indicated by microscopic hematuria and mild proteinuria recurrent episodes of gross hematuria following upper
is common. Serum IgA levels may be elevated. Renal respiratory infections; each episode lasts for 2-5 days.
biopsy shows mesangial proliferation with mesangial An acute nephritic or nephrotic syndrome is rarely the
deposition of IgA. Most patients recover without any initial manifestation. Renal histology sh ows mesangial
specific treatment. However, long-term observation is proliferation of varying severity. Patients \1.·ith
necessary to detect insidious renal damage. Rarely, a hematuria and non-nephrotic proteinuria are treated
using angiotensin-converting enzyme inhibitors.
Therapy with corticosteroids and alkylating agents is
indicated in patients with nephrotic range proteinuria.
deranged renal function or tho se with sen~ re
histological changes.
Lupus Nephritis
Patients with systemic lupus erythematosus variably
present with asymptomatic proteinuria and / or hernaturia,
acute nephritic syndrome and nephrotic syndrome. Renal
biopsy rnay show almost normal glomeruli. focal or diffuse
proliferative GN or membranous nephropathy. Irnmuno-
fluorescence studies show mesangial and capillary wall
deposits of all immune reactants (full-house deposition).
Antinuclear and double-stranded DNA autoantibodies are
~
Fig. 17.9: Large cellular crescent with compression of glomerular
tuft (Masson trlchome x 200)
present in most cases with lupus nephritis; C3 le\·els are
reduced.
Remissions and relapses and progressive renal damage
are characteristic. Infections and end stage renal disease
are the chief cause of mortality.
I
- 472 Essential Pediatrics
I
resultant fall in plasma oncotic pressure leads to interstitial Prognosis Good; relapses stop Variable progression of
edema and hypovolemia. This stimulates the renin- by second decade renal damage
angiotensin-aldosterone axis and antidiuretic hormone MPGN: Membranoproliferative glomerulonephritls
Disorders of Kidney and Urinary Tract
j 473 -
Ag. 17.11: (a) Renal histology in a 4-year-old boy with steroid-dependent nephrotic syndrome. There Is normal morphology of
glomerular capillary loops, mesanglal matrix and cells suggestive of minima! change disease; (b) Histological features in a
6-year-old girl with steroid-resistant nephrotic syndrome secondary to focal segmental glomerulosclerosis. Note the hilar sclerosis
involving large areas of the glomeruius and adhesions to the Bowman's capsule
immunity, which through yet undefined mechanisms increasing edema, urine output may fall . The blood
alters the permselectivity of the glomerular filter, resulting pressure is usually normal; sustained elevation suggests
in proteinuria. A significant proportion of patients shows the possibility of significant glomerular lesions. The
Th2 polarization; some also show perturbation in the T- bloated appearance and relative well-being of the child is
regulatory /Th17 axis. misleading and after the loss of edema, severe muscle
wasting is revealed. Infections may be present at the onset
Clinical Features and during relapses.
The onset is insidious with edema first noticed around
Laboratory Findings
the eyes and subsequently on legs. It is soft and pits easily
on pressure. Gradually, edema becomes generalized, with Urine examination shows heavy (3 - 4+) proteinuria. Gross
ascites, hydrothorax and hydrocele (Fig. 17.12). With hematuria or persistent microscopic hematuria suggests the
likelihood of significant glomerular lesions; hyaline and
granular casts are present. Serum albumin is low and values
below 1 g/ dL are often obtained. Hypercholesterolernia
may impart a milky appearance to the plasma. Blood urea
and creatinine values are within the normal range except
when there is hypovolernia and fall in renal perfusion.
Blood levels of IgG are low and those of IgM elevated;
C3 level is normal. The severity of glomerular damage is
reflected in the passage of proteins of large molecular
weight, chiefly globulin.
Evaluation at onset of nephrotic syndrome includes:
(i) urinalysis for proteinuria, red cells, casts; (ii) blood
levels of urea, creatinine, albumin, cholesterol; (iii)
complete blood counts; and (iv) tuberculin test. Depen-
ding on clinical and laboratory findings, the following
additional tests may be required: (i) C3 and antistrepto-
A renal biopsy is not required to con£m:n the ~iagnosis Table.17 •8•. Definitions regarding
• course of nephrotic
. syndrome'
.
of MCNS prior to starting treatment. A biopsy is recom- . . . Urine albumin nil or trace (or protefnuria <4 m~
Rem1ss1on. . ·
mended in children with atypical features at the onset (age m2fhr) for 3 consecutive early morning specimens
below 12 months, gross or persistent microscopic hema- . ur·ine albumin 3+ or 4+ (or proteinuria >40 mg/m2fhr)
Reapse.
I . · h · b ·
turia, low blood C3, hypertension or impaired renal for 3 consecutive early morning specimens, aving een 111
function). Patients who continue to show nephrotic range remission previously
proteinuria despite appropriate steroid therapy require a Frequent relapses: Two or m?re relapses in initial six months
biopsy to determine the underlying disorder. or four or more relapses in any 12 months
Stero1"d dependence: Two consecutive frelapses when on
Management of lnltlal Episode alternate day steroids or within 14 days o 't1s d'1scont'inuat1011
.
The child should receive a high protein diet. Salt is restric- Steroid resistance: Absence of remission despite therapy with
ted to the amount in usual cooking with no extra salt given. daily prednisolone at a dose of 60 mg/m 2/day for 4 weeks and
Any associated infection is treated. Patients should be alternate day for next 4 weeks
screened for tuberculosis. Diuretics are administered, only
if edema is significant. They should be used cautiously and Management of Relapse
overzealous fluid loss avoided. Frusemide (1-4 mg/kg/
Relapses are often trigger~d by minor. infection.s.
day in 2 divided doses) alone or with an aldosterone
Symptomatic therapy of infectious illn~ss ~ght result m
antagonist, spironolactone (2-3 mg/kg/ day in 2 divided
remission of low grade (1-2+} protemuna. However,
doses) is adequate. Therapy with corticosteroids results in
persistence of 3-4+ proteinuria requires treahnent for relapse.
abolition of proteinuria (remission) usually by 10-14 days,
Prednisolone is given at a dose of 60 mg/ m 2 /day until
diuresis and loss of edema.
protein is negative/ trace for three consecutive days, and then
The first episode of nephrotic syndrome should be on alternate days at a dose of 40 mg/m2 for 4 weeks. Thus,
treated adequately, both in terms of dose and duration of treabnent for a relapse usually lasts for 5--6 weeks.
corticosteroids, since this is considered an important The first2-3 relapses are treated in the manner described
determinant of long-term course. Only prednisolone and
above. Once the pattern of relapses is known, therapy is
prednisone are of proven benefit in the treatment of individualized. Patient~ with infrequent relapses continue
proteinuria. Either of these agents is given at a dose of
to receive treatment for individual relapses as outlined
60 mg/m2 /day (maximum 60 mg) in single or divided
above.
doses for 6 weeks, followed by 40 mg/m2 (maximum
40 mg) as a single morning dose on alternate days for the Frequent Relapses and Steroid Dependence
next 6 weeks. Therapy with corticosteroids is then
stopped. Extending initial therapy beyond 12 weeks Patients with frequent relapses or steroid dependence
increases the risk of corticosteroid toxicity without require prolonged treatment in order to maintain disease
significant benefits, and is not recommended. remission.
Long-term Alternate Doy Prednlsolone
Parent Education
Following treatment of a relapse, the dose of prednisolone
The parents should be explained about the disease and is tapered to maintain the patient in remission; usually a
the usual outcome and their cooperation ensured. They small dose is given on alternate days for 9- 18 months
are taught how to examine urine for protein, which (Table 17.9). This strategy is effective in maintaining
should be done periodically to detect a relapse early. remission in many patients. Since infections precipitate
During the periods of remission, no dietary restrictions relapses, administering the same small dose daily for
are imposed. 5-7 days starting at onset of infections m ay prevent
relapses. Relapses, while on this therapy, are treated .as
Subsequent Course described above. Patients with repeated relapses, while
A small proportion of patients have only a single episode on long-term therapy, should be considered for treatment
of the illness, while the majority shows relapses. Some with a steroid- sparing agent.
patients have three or less relapses in a year (infrequent
relapsers), while others have four or more relapses Steroid-Sparing Agents
(frequent relapsers) (Table 17.8). About 15% remain in The additional use of an alternative agent should be
remission while on prednisolone therapy and relapse considered in patients with: (i) prednisolone threshold (for
whenever the dose is reduced or within 2 weeks of its maintaining remiss.i.on) higher than 0.5-0.7 mg/ k~ ~n
discontinuation (steroid dependent). About 10% patients alternate days, or (11) features of corticosteroid toxic! J
either do not respond to the initial treatment with (growth failure, hypertension, cataract). The agents use.~
prednisolone, or do so transiently and later cease to usually in successive order, are listed below and 1
respond (steroid resistant). Table 17.9.
Disorders of Kidney and Urinary Tract 1475 -
,-
l
~
Table 17.9: Therapy for steroid-sensitlve.~ephrOtic-~yncirome
Agent Dose Duration Adverse effects
Prednisolone 0.3-0. 7 mg/kg on 9-18 months Cushingoid body habitus, hypertension, short
alternate days stature, cataract, hirsutism
Levamisole 2-2.5 mg/kg on alternate days 1-2 years Leukopenia, rash, flu-like symptoms
Cyclophos- 2-2.5 mg/kg/day 12 weeks Leukopenia; alopecia; gonadal toxicity; nail
phamide* discoloration. (Hemorrhagic cystitis; nausea and
vomltin'g are more common with IV administration)
Mycophenolate 600-1000 mg/m 2/day or 1-3 years Gastrointestinal discomfort, diarrhea; leukopenia
mofetil 20-25 mg/kg/day
Cyclosporine (CyA)" CyA: 4-5 mg/kg/day 12-36 months Acute and chronic nephrotoxicity, elevated
Tacrolimus (Tac)* Tac: 0.1-0.2 mg/kg/day transaminases (both agents); hirsutism, gum
hyperplasia, hypertension or hyperlipidemia
(CsA > Tac); hyperglycemia, neurotoxicity with
headache and seizures (Tac > CsA)
Rituximab* 375 mg/m2 IV once a week 1-2 doses Infusion reactions (fever, rash, bronchospasm);
neutropenia
• Preferred earlier, if relapses are life-threatening (associated with peritonitis, other serious infections or thrombosis) or in presence of significant
steroid toxicity
Levamisole: This immunomodulator is effective in steroid-sparing agents or show high steroid threshold with
reducing relapses in patients with frequent relapsing or steroid toxicity. Cyclosporine A or tacrolimus is
steroid-dependent nephrotic syndrome. After inducing administered, in two divided doses, for 12- 24 months
remission, levamisole is administered at a dose of 2- aiming for respective trough levels of 80-120 ng/mL and
2.5 mg/kg on alternate days. Alternate day prednisolone 3-7 ng/mL. Both agents hav e strong steroid-sparing
is given in decreasing doses, until a dose of 0.3-0.5 mg/ potential, with steroid discontinuation achieved in most
kg is reached, for 3-6 months; it is occasionally possible patients over 6-9 months.
to discontinue steroids altogether. Treatment with Adverse effects are common and include acute and
levamisole is given for 1-2 year or longer. The chief side chronic nephrotoxicity. A renal biopsy is done after
effect is leukopenia, which should be monitored every 2-3 years of continuous therapy. Patients receiving
2 months; others include flu-like symptoms and rash. cyclosporine have cosmetic side effects (hirsutism, gum
hyperplasia), hypertension and hypercholesterolemia.
Cyclophosphamide: Treatment with cyclophosphamide Treatment with tacrolimus is associated with risk of
and alternate day prednisolone is effective in many hyperglycemia, elevated transaminases, diarrhea, tremors,
patients with frequent relapsing or steroid-dependent headache and seizures.
nephrotic syndrome. A 12-week course of treatment may
induce long-lasting remission in 30-40% cases. Side effects Rituximab: This monoclonal anti-CD20 antibody has been
include leukopenia, nausea and vomiting; a high fluid used with success in patients with steroid dependent
r intake is ensured to prevent hemorrhagic cystitis. There
is risk of gonadal toxicity and malignancies, although at
nephrotic syndrome, with remission lasting 6-18 months.
This agent appears to be useful in patients who fail to
the doses and duration used, these risks are minimal. The respond or show toxicity with other therapies.
alkylating agent, chlorambucil has significant additional
Complications in Nephrotlc Syndrome
toxicities and a low margin of safety, and is not
recommended~ · The patient should be maintained in remission, as far as
possible. Relapses should be promptly treated so that the
Mycophenolate mofetil: Prolonged treatment with this child does not develop more than minimal edema.
agent is useful in reducing relapse rates and corticosteroid
sparing. The lack of renal, hemodynamic and metabolic Edema
toxicity makes it an alternative to calcineurin ~ibitors. Edema is controlled with salt restriction and oral hydro-
Chief side effects include gastrointestinal discomfort, chlorothiazide or frusemide for a few days. Salt must
diarrhea and leukopenia. The dose of the medication is not be totally stopped and the usual amounts used in
600-1000 mg/m2 /day or 20-25 mg/kg/day in two cooking should be allowed. For massive edema, higher
divided doses for 12- 36 months. Tapering doses of doses of frusemide along with spironolactone are needed.
prednisolone are given for -6 months. Infusion of albumin is necessary in cases where serum
Cyclosporine and tacrolimus: Therapy with either of these albumin levels are low causing poor renal perfusion and
agents is indicated in patients that fail to benefit with other oliguria.
-476 j Essential Pediatrics
.,..,,.17~10;·--~~~~~-o.-*~
--------._,,
Ag1Jnl D{)§{J Durathn EffJCae/ , M~erse efl~
C1Jclruwrln fnhfblfort
C-1rJ<JS;J>Ofifj~ ' 4-fi ff¥,;"¥.fJ/d::i:J 12-<;e rra""'."d. YJ-&:f~ See Tatle 17.9
ftil>fOliffitJ§ (J, 1--0,2 fWJf!l'fl/~/ 12J~f(ilClri'°''~ 70-e&%
C1cfopllotphtmta.
f/J(j-7rf
lfllf1Jo/gf}'.11J{}
· A rrVJjrrr, g~ ~ lEi.Ao:-"~ a~ r.zw.:ea a.~ •I04"l'lffir.g;
Oral 24,5 rnrJl'QJIOO'J 12 -11r;qm
20-25'% gr'~J WY.fdlr, r~ c~
Hirth doH cort1C<Jt1.9rofd• vlfth cy~kfe
MM.tt1jlpr9rJr1l§l,Aono 20-00 rfl/'$'1-.g fV 'P~
00 20-zoah H'~...n. rr,rpr~Ja. l'll, n;agfycemia. &sroid
aftemate psi/cfliosis, sjstsfrac rrtec00os
OO'j~ Y. 6
tr<mtlflt:nt fo the achievement of compl€:te remission, although ultrastructural abnormalities of the glomerular
occummm uf partial reml.%lon ls also satisfactury, Patients basement membrane are present at birth.. Elevated levels
who mlprmd to tn:atmcnt do f,o within 3-6 mcmths. of alpha-fetoprotein (AFP) in maternal serum and
Adj1111 c:tive th£:rnpy with angiotensin-conv€:rting amniotic fluid enable antenatal screening. The clinical
em:yrrw inhibitor;~ fo,~, enalapril 0.3-{),6 mg/kg/ day, course is complicated by failure to thrive, recurrent
rnmlpril 6 mg/ mzI cfoyJ i~ a1;bociated with decrease in infections, hypothyroidism and progression to renal
prutdnurla und CtJntroJ of hypertension. Adverse effects failure by 2-3 years.
Include dry OJU~~h, hyperY..alcmia and decline in renal Patients with Denys-Drash syndrome show mutations
fur1dlm1. Anglotcn1'in receptor blockers (e.g. losartan, in the WT1 gene, congenital nephrotic syndrome, male
valimrltin) may b(! U!'-ed in caw of persis tent dry cough pseudohermaphroditism and high risk of bilateral Wilms'
with ACE inhil?ilor1:J1 or a B add-on therapy for better tumor. Renal histology is characterized by diffuse
antlprolcinurlc effect Therapy with HMG coenzyme-A mesangial sclerosis and there is progressive renal failure.
rccJuctaw Jnhibitori; ia adviB<!d for subjects with persistent Other causes of congenital nephrotic syndrome include
hypt'rd1,>lcHlcrolcmia. infections (congenital syphilis, cytomegalovirus disease,
JJypcrlcnaion mul't be controlled and infections mana- toxoplasmosis) and mutations in PLCE1 or NPHS2 genes;
g<:<.1 appropriatcly. Edema is minimi:r...ed with judicious use rarely renal histology may be normal (minim.al change
of tllurclicB. The UHC of intravenous albumin is indicated in nephrotic syndrome) or show focal segmental glomerulo-
cascfl with (l) ayrnplomatichypovolcmia, (ii) symptomatic sclerosis. Therapy of patients with congenital nephrotic
ccJcma "'(iii) marked ascilcs that is causing respiratory syndrome includes appropriate nutrition, control of
compromii;e, Jn cnscs with hypovolemia, 10-20 mL/kg ~f edema, thyroxin supplements and reduction of proteinuria
4..5-S'Y,, nlbumin should be infused. Severe symptomatic through ACE inhibitors and/ or indomethacin.
edema or ilHCilcH may be treated with 0.75-1 g/kg of 20% Regular use of IV albumin infusions (every 2-3 weeks)
albumin, lnf uHed over 2 hours, to expand the circulating avoids marked hypoalbuminemia and reduces the need
volumu followed by frusemide l mg/ kg. Close monitoring for hospitalization for managing anasarca.
l11cBt1cnllnl to avoid fluid overload and pulmonary edema.
Suggested Reading
Congenital Nephrotlc Syndrome • Ellis D. Pathophysiology, evaluation, and management of edema
in childhood nephrotic syndrome, Front Pediatr 2016; 3:11L
Congenltol ncphrotic syndrome present ~n th~ first
• Gulati A, Bagga A, Gulati S, on behalf of the lndian _Society _of
3 months of life with anasarca, hypoalbummemia and Pediatric Nephrology. Guidelines for management of children with
ollguria. The ctlolob'Y of congenital ncphrotic s~ndro~e steroid resistant nephrotic syndrome. Indian Pediatr 2009; 46:35-47,
Is heterogeneous. The 'Finnish' form of the disease. is
Inherited in an nutosomal recessive manner, with
mutations in the gene encoding nephrin (NP.HS1_J. ~he
• Indian Pediatric Nephrology Group. Indian Academy of Pedia~cs.
Management of steroid sensitive nephrotic syndrome, Revised
guidelines. Indian Pediatr 2008; 45:203-14,
1
charnctcriHtic renal histology with microcystic d1Jat~on • Sinha A, Menon S, Bagga A. Nephrotic syndrome: State-of-the-
of proximal tubules is seen after a few months of life, art. Curr Pediatr Rep 2015; 3:43-<JL
CHRONIC GLOMERULONEPHRms insufficiency associated with ~~tisfactory urin~ output,
and minimal urinary abnormalities suggest the diagnosis
Orronic GN is not a single disease entity, but comprises Leukocytes and eosinophils are frequently seen in th~
advanced stages of several fonns of GN. In most cases, the
urine.
glomerular disease is primary and not part of a systemic A renal biopsy establishes the diagnosis and helps assess
disorder. However, chronic GN may occur in systemic severity. Drug-related interstitial nephritis is ~eated With
lupus erythematosus, microscopic polyarteritis, familial stoppage of the offending drug; treatment ~1t~ corticos-
nephropathies and nephropathies due to drugs and toxins. teroids is beneficial. The treatment of chrome interstitial
Variable glomerular deposition of immunoglobulin,
nephritis is symptomatic.
complement and fibrin is found on immunofluorescence
studies. Renal biopsy examination in early stages shows Suggested Reading
several patterns, while later the histologic changes are
• Ulinski T, Sellier-Leclerc AL, Tudorache E, et al. Acute
nonspecific. Most glomeruli are sclerosed with corres- tubulointerstitial nephritis. Pediatr Nephrol 2012; 27:1051-7.
ponding tubular, interstitial and vasrular changes.
The patient may be asymptomatic and the disease detected Urinary tract infection (UTI) is a common medical problem
on routine urine examination. Others may show failure in children, affecting 3-10% girls and 1- 3% boys. They
to thrive, persistent anemia, moderate to severe hyper- are an important cause of morbidity and might result in
tension, edema, nocturia, microscopic or gross hematuria, renal damage, often in association with vesicoureteric
bone pains and deformities. reflux (VUR). During infancy, UTis are equally common
in boys and girls because the route of infection is often
Differential Diagnosis hematogenous and boys have a higher incidence of
urinary tract anomalies. Beyond infancy, the incidence is
It might be difficult to distinguish chronic from acute GN.
higher in girls.
The presence of anemia, growth retardation, hypertensive
retinopathy, left ventrirular hypertrophy and radiological
Microbiology
skeletal changes indicate impaired renal function of long
duration. Examination of the renal biopsy is valuable. UTis are chiefly caused by E. coli the predominant
Urinalysis shows proteinuria, hematuria, white cells and periurethral flora, others include Klebsiella, Enterobacter
casts. Urine specific gravity is fixed and low (around 1.010). and Staphylococcus saprophyticus. Proteus and Pseudomonas
Blood urea and creatinine levels are raised and the infections occur following obstruction or instrumentation;
glomerular filtration rate less than 30 mL/min/1.73 m 2• Candida infection occurs in immunocompromised children
Ultrasonography shows small kidneys with regular outline. or after prolonged antimicrobial therapy.
There is no specific treatment for chronic GN. Treatment Recurrent UTis are observed in 30-50% children usually
with immunosuppressive drugs does not offer any benefit. within 3 months of the first episode. Predisposin~ factors
The blood pressure should be controlled and infections for recur.r ent UTI include female sex, age below 6 months,
treated. If renal function is compromised, the treatment is obstructive uropathy, severe vesicoureteric reflux (VUR),
that of advanced chronic kidney disease. voidin~ d)'."sfunction, constipation and r epea ted
cathetenzahon, e.g. for neurogenic bladder. Children
with malnutrition and those receiving immuno-
INTERSTITlAL NEPHRITIS
suppressive therapy are also susceptible.
This is focal or diffuse inflammatory reaction of renal
interstitium with secondary involvement of tubules and Clinical Features
rarely, glomeruli. Acute interstitial nephritis is usually due Neonates show features of sepsis with fever, vomiting,
to infections or drugs (e.g. ampicillin, cephalosporins). diarrhea, jaundice, poor weight gain and lethargy. The
Common causes of chronic interstitial nephritis include older infan: has unexplained fever, frequent micturiti~n
urinary tract obstruction and vesicoureteric reflux. and occas10nally convulsions. Gross hematuria is
Interstitial nephritis may be a feature of a systemic uncommon. The presence of crying or straining during
disorder (e.g. systemic lupus, vasculitis, associated with voiding, dribbling, weak or abnormal urine stream and
uveitis); autoantibodies to tubular basement membrane palpable bladder suggest urinary obstruction.
are found in some cases. It is difficult to distinguish between infection localized
The clinical features are nonspecific and include to the bladder (cystitis) and upper tracts (pyelonephriti5l·
abdominal pain, anorexia, pallor, headache and edema. The distinction is not necessary since most UTI in chiJdr.ert
Hypertension is absent. The presence of progressive renal below 5 years of age involve the upper tracts. Patients with
479
high fevc.r (>39°C), systemic toxicity, persistent vomiting,
dehydration, renal angle tenderness or raised creatinine are Tabfe 17.11: Antimicrobials for treatment of UTI
consi~ered as complicated. Patients with low grade fever, Medication Dose (mg/kg/day)
dysuna, ~requency and urgency and absence of symptoms Parenteral
o~ c~m~hca.te~ UTI are considered to have simple UTI. This Ceftriaxone 75-100, in 1-2 divided doses IV
d1stmchon is important for purposes of therapy.
Cefotaxime 100-150, in 2-3 divided doses IV
I~~ortant f~atur~~ on ~valuation include history of Amikacin 10-15, single dose IV or IM
strammg ~t .m 1ctunhon, incontinence or poor urinary Gentamicin 5-6, single dose IV or IM
stream, v01dmg postponement and surgery for meningo-
Coamoxiclav 50-75 of amoxicillin, in 2 divided doses IV
~yelocele or.anorectal malformation. Finding of palpable
ktdney~s), distended bladder, tight phimosis or vulva! Oral
synech.1ae a~d neurological deficit in lower limbs suggest Cefixime 8-10, in 2 divided doses
a pred1sposmg cause. Coamoxiclav 3D-50 of amoxicillin, in 2 divided doses
Ciprofloxacin 10-20, in 2 divided doses
Diagnosis Ofloxacin 15-20, in 2 divided doses
The diagnosis of ~TI is base~ on growth of significant Cephalexin 50-70, in 2-3 divided doses
number of organisms of a single species in the urine.
Significant bacteriuria is a colony count of >105/mL of a or following treatment, unless symptoms fail to resolve
sing~e species in a de.an catch sample. Urine may be despite 72 hours of therapy symptoms recur, or
obtained by suprapub1c bladder aspiration or urethral contamination of the initial culture is suspected.
catheterization in children below 2 years. Any colonies
Imaging Studies
on suprapubic aspiration and >50,000/mL on urethral
catheterization are considered significant. The occurrence Following treatment of thefirst episode of UTI, plans are made
of significant bacteriuria in absence of symptoms is termed for evaluation of the urinary tract. The aim of imaging studies
asymptomatic bacteriuria. is to identify urologic anomalies that predispose to
The presence of >10 leukocytes per mm 3in fresh p yelonephritis, such as obstruction or v esicoureteric
uncentrifuged sample, or >5 leukocytes per high power reflux, and detect evidence of renal scarring. Renal
field in centrifuged sample is useful for screening. Dipstick ultrasonography is useful in detecting hydronephrosis or
examination, combining leukocyte esterase and nitrite, has anomalies of the urinary bladder and may be performed
moderate sensitivity and specificity for detecting UT!. even during therapy for UTI. Micturating cystourethrogram
is necessary for the diagnosis and grading of VU R
(Fig. 17.13) and defines urethral and bladder anatomy.
Treatment
This procedure may be performed 2-4 weeks after
Once UTI is suspected, a urine specimen is sent for culture treatment of the UTI. DMSA scintigraphy detects cortical
and treatment started. Infants below 3 months of age and scars, which are regions of decreased uptake with loss of
children with complicated UTI should initially receive parenteral renal contours or presence of cortical thinning with
antibiotics. The initial choice of antibiotics is empiric and is decreased volume (Fig. 17.Sa). In order to distinguish scars
modified once culture result is available. While a third from reversible changes of pyelonephritis, this procedure
generation cephalosporin is preferred, therapy with a is done 3-4 months after therapy for UTI.
single daily dose of aminoglycoside is also safe and These investigations should be performed judiciously,
effective (Table 17.11). Once oral intake improves and such that sufficient evaluation is done but at minimum
symptoms abate, usually after 48-72 hours, therapy is risks of radiation exposure. The recommendations of the
switched to an oral antibiotic. The duration of treatment for Indian Society of Pediatric Nephrology ·on evaluation
complicated UTI is 10-14 days. Older infants and patients following the first UTI are summarized in Table 17.12. All
with simple UTI should receive treatment with an oral infants (<1 year) require evaluation using ultrasonography,
antibiotic for 7-10 days. Adolescents with cystitis may MCU and DMSA scan, since they are at the highest risk of
receive shorter duration of antibiotics, lasting 72 hours. UTI recurrence and scarring. Early detection of high grade
Patients with asymptomatic bacteriuria do not require treatment. VUR or obstructive uropathy allows interventions to
All children with UTI are encouraged to take enough prevent progressive kidney d ama ge. Imaging is less
fluids and empty the bladder frequently. Routine aggressive in older children, but patients with recurrent
alkalization of the urine is not necessary. With appropriate UTI require detailed evaluation for anomalies.
therapy, fever and systemic toxicity reduce and urine
culture is sterile within 24-36 hours. Failure to obtain such Preventing Recurrent UTI
results suggests either lack of bacterial sensitivity to the Prophylactic antibiotics are administered to young infants
medication or presence of art underlying anomaly of the until results of imaging are available. The medication used
urinary tract. A repeat urine culture is not required during should be effective, nontoxic and not alter the gut flora or
4eo I Essential Pediatrics ·
Suggested Reading
• American Academy of Pediatrics, Subcommittee on Urinary tract
infections. Urinary tract infection: Clinical practice guideline for
the diagnosis and management of the initial UTI in febrile infants
and young children 2 to 24 months. Pediatrics 2011;128:593-{;10.
• Garcia-Roig ML, Kirsch AJ. Urinary tract infection in the setting of
I
vesicoureteral reflux. FlOOORes. 2016 June 30;5.
• Indian Society of Pediatric Nephrology. Revised statement on Fig. 17.13: Mlcturating cysotourethrogram showing bllaterol
management of urinary tract infections. Indian Pediatr 2011; grade V veslcoureterlc reflux In a glrl with recurrent UTI. Note me
48:709-17. . dilatation, tortuoslty of ureters and cupping of the calyces
Disorders of Kidney and Urinary Tract I 4a1 I
prophylaxis, or in patients who show deterioration of renal
function. Ureteric reimplantation has cure rates of 95-97%.
The precise indication for endoscopic submucosal
injection of dextranomer /hyaluronic acid copolymer
(Deflux) at ureteric orifices is not defined. While results
are satisfactory in centers with expertise, a significant
proportion of patients, particularly those with bowel
bladder dysfunction, may show persistence and/ or
recurrence of reflux.
II Ill IV v
Fig. 17. 14: Grading of vesicoureteric reflux (\/UR) on mlcturating Follow-up
cystourethrogram. Grade I: VUR does not reach the renal peMs; Repeat imaging is required after 18-36 months in patients
Grade II: VUR extending up to the renal peMs without dilatation of with grades III-V VUR. Radionuclide cystogram, with
peMs or calyceal fornices; Grade Ill: VUR extending up to the kidney.
lower radiation exposure and higher sensitivity, is preferred
with mild dilatation or tortuostty of the ureter and renal peMs. and
no or minor blunting of the calyceal fornices; Grade N: Moderate for follow-up evaluation. Urinalysis and measurement of
dilatation or tortuostty of the ureter. renal peMs and fomices. with height, weight and blood pressure are done annually. Urine
complete obliteration of the sharp angles of the calyceal fornices, cultures are obtained, if the patient has symptoms of UTI.
bUt normal appearance of the papillary impressions; Grade V: Gross
dilatation and tortuostty of the ureter. renal peMs and calyces. with Screening of Slbllngs and Offspring
loss of papillary Impressions on calyces
VUR is inherited in an autosomal dominant manner with
incomplete penetrance; almost one-third siblings and
Vesicoureteric reflux offspring of patients show VUR. Ultrasonography is
recommended to screen for presence of reflux; further
Grades I and II
imaging is performed, if ultrasonography is abnormal.
Grades Ill to V
•
Antibiotic prophylaxis
..
Antibiotic prophylaxis till 5-year-old
Outcome
till 1-year-old Continue beyond 5 years, if bowel Primary VUR tends to resolve by 6-10 years of age. Factors
bladder dysfunction is present favoring resolution are younger age and low grade and
unilateral VUR. The rate of resolution is 70-90% for grades
Breakthrough febrile UTI
/ Consider surgery /
I-III and 10-35% for higher grades.
Reflux Nephropathy
Fig. 17 .15: Management of vesicoureteric reflux. Medical This is characterized by renal cortical scarring, pre-
therapy Is based on the principle that VUR resolves over time, dominantly at the poles. The underlying calyces lose their
and prophylactic antibiotics maintain urine sterility and prevent normal concave shape and show clubbing. Such scarring
Infections while awaiting spontaneous resolution. Reflux takes occurs early in life when the kidneys are still growing.
longer to resolve, if associated with bowel bladder dysfunction
Reflux nephropathy is an important cause of hypertension
or If high grade reflux is present; such patients require prolonged
and end stage renal disease in children.
prophylaxis. Surgical correction of VUR Is indicated, if break-
through infections occur, since significant parenchymal injury
Suggested Reading
may occur with pyelonephritis
• Neveus T, von Gontard A, Hoebeke P, et al. The standardization
of terminology of lower urinary tract function in children and
low after 4-5 years of age, prophylaxis may be adolescents: report from the standardization committee of the
discontinued in children older than 5 years with normal International Children Continence Society. J Urol 2006;176:314-24.
bowel and voiding habits, even if mild to moderate reflux • Peters CA, Skoog SJ, Arant BS, et al; American Urological
persists. Association Educa tion ond Reseilrch. Summary of the AUA
guideline on mmrngement of primary vesicoureteral reflux in
Other measures to be instituted include a liberal fluid children. J Urol 2010;184,1134-14.
intake, regular and complete bladder emptying and local • Skoog SJ, Peters CA, Arant BS, et al. American Urological
toilet. Constipation should be avoided. A close follow-up Association Education and Research. Pediatric vesicoureteral reflux
is required for occurrence of breakthrough UTI. guidelines panel summary report: Clinical practice guidelines for
The indications for surgical correction of primary VUR screening siblings of children with vesicoureteral reflux and
are limited and include poor compliance or intolerance to neonates/ infants with prenatal hydronephrosis. J Urol 20 10;
184:1145-51.
I
rnedical treatment. Patients with grades III to V reflux may
• Yeung CK, Chowdhary SK, Sreedh B. Minimally invas ive
be offered surgical repair, if they have breakthrough management for vesicoureteral reflux in infants and yo ung
febrile UTI, if parents prefer surgical intervention to children. Clin Perinatol 2017;44:835-49.
- - 4a2 I
b ack mo. t the circulation across the damaged tubular
ACUTE KIDNEY INJURY b . f . .
epithelium and tubular o sultruc~on . ro~ 10~~hon of
Acute kidney injury (AKI) or acute renal f~ilure (~)
cas t s an
d cellular debris res ts m o 1guria.
' bl b . f .
1 1 e early
f fl .
denotes an acute impairment of renal function resulting stages are rapidly revers1 e y m us1on o uids,
in retention of nitrogenous wastes and other metabolic or severe ischemia may lead to acute tubular
prolonged 'f .h
derangements. Oliguria or anuria is a prominent feature, necrosis. Nephrotoxic agents ca~se um orm ep1! eli,11
though rarely urine output may be normal. damage, especially in the proximal tubules, without
disruption of tubular basement membrane.
Definition and Classlflcatlon In acute tubular necrosis, examination may be normal
In the absence of a standard definition of ARF, the term except for dehydratioi:· The o.liguric pl~ase las~s about
acute kidney injury (AKI) is proposed to reflect the entire 3-10 days, during which period the b1ochem1c~l and
spectrum of the disorder. Patients are diagnosed to have · clinical abnormalities gradually worsen, more rapidly if
AKI, if there is abrupt reduction in kidney function, infection, trauma and bleeding are associated. Subse-
defined as either (i) absolute increase in serum creatinine quently, urine output increases steadily. A diuretic phase
of more than or equal to 0.3 mg/dL over 48 hours, or a may be observed, usually lasting for a week, during which
percentage increase of more than or equal to 50% from large amounts of ·w ater and electrolytes may be lost.
baseline in last 7 days, or (ii) reduction in urine output
(less than 0.5 mL/kg/hr for >6 hours). The inclusion of Approach to Evaluation
both an absolute and a percentage change in creatinine History provides clues to the underlying cause of AKI. It
allows for variations related to age, gender and body mass is important to examine for prerenal factors that lead to
index. Table 17.14 shows the classification of AKI. renal hypoperfusion. A history of diarrhea, vomiting, fluid
or blood loss is taken and assessm.ent of fluid intake in
Incidence and Etiology the previous 2-1 hours made . In patients w ith nephro-
The etiology of AKI is classified as prerenal, intrinsic renal toxicity or intravascular hemolysis, urine output is often
or postrenal (Table 17.15). The chief causes of AKI include not diminished (nonoliguric renal failure).
acute tubular necrosis (ATN) secondary to hypovolemia, Laboratory evaluation (Table 17.16) includes blood
sepsis and nephrotoxic agents, acute glomerulonephritis counts and estimation of blood levels of urea, creatinine,
and hemolytic uremic syndrome (HUS). Postrenal failure electrolytes, pH and bicarbonate and urinalysis. In
is consequent to mechanical obstruction in the collecting prerenal azotemia, the renal tubular function is intact and
system. In developing countries, common causes include reabsorption of water and sodium is increased. The urine
septicemia with multiorgan failure, HUS, gastroenteritis is concentrated with low sodium content. Impaired
with dehydration, postinfectious and crescentic GN and tubular function in intrinsic renal failure results in
intravascular hemolysis. In developed countries, AKI increased sodium excretion and failure to concentrate
follows major surgical procedures, HUS and severe urin~. Determination of urine sodium and osmolalitv ,md
systemic infections. frach.o nal excretion of sodium help in differenti~ting
functior:ial oliguria (prerenal) from established (intrinsic)
Pathophyslology renal fm~ure. U.ltras~nography is a useful imaging tool in
Prerenal failure is secondary to systemic hypovolemia or renal failure smce it allows visualization of the pelvi-
renal hypoperfusion, where renal tubular injury leads to calycea~ system and assessment of the renal size, structurnl
marked decline in glomerular filtration and renal blood an:alies and calculi, and does not depend on renal ft mction.
flow, often by 50 to 75%. Leakage of glomerular filtrate d ' ostt. pati~ntsb\~ith AKI do not require a renal biopsy.
1n ica 10 ns or iopsy are: (i) rapidly progre:':' i\·e or
Stage
. .
Serum creatmme
:~~le 17.14: Staging of acute kidney injury (A~l~baseci°on KDIGO criteria* · •
Urine output · · · · .1
1 Increase in serum creatinine of <':0.3 mg/dl over L
48 hours or <':150% to 200% (1.5- to 2-fold) from ess than 0.5 mUkg per hour for >6 hours
baseline in last 7 days
2 Increase in serum creatinine to more than 200%
to 300% (>2- to 3-fold) from baseline Less than 0.5 mUkg per hour for > 12 hours
3••
Increase in serum creatinine to more than 300%
hours Less than 0.3 mUkg per
. · for 12
hour for 2 4 hours, or anuna
(>3-fold) from baseline (or serum creatinine
;::4.0 mg/dL with acute increase of ;;>:0.5 mg/dL)
• · Table 11.1s: lmportant causes 'of"acute kidney injury Table 17.16: Investigations In patients with ~cute kidney Injury
Prerenal failure Complete blood counts
Hypovolemla (dehydration, blood loss, diabetic ketoacidosis) Blood: Urea, creatlnine, sodium, potassium, calcium,
Third space losses (septicemia, nephrotic syndrome) phosphate, pH, bicarbonate
Congestive heart failure Urinalysis; culture
Perinatal asphyxia Urine: Sodium, osmolallty, fractional excretion of sodium
Drugs (ACE inhibitors, diuretics) Chest X-ray (for fluid overload, cardiomegaly)
Intrinsic renal failure Abdominal ultrasonography
Acute tubular necrosis Investigations to determine cause
Prolonged prerenal insult (see above) Peripheral smear examination, platelet and reticulocyte count,
Medications: Aminoglycosides, radiocontrast, NSAIDs complement (C3), LOH levels ; stool shlgatoxin (suspected
Exogenous toxins: Diethylene glycol, methanol hemolytic uremic syndrome)
lntravascular hemolysis, hemoglobinuria Blood ASO, C3, antinuclear antibody, antlneutrophil cytoplasmic
Tumor lysis syndrome antibody (suspected acute, rapidly progressive GN)
Hemolytic uremic syndrome: Infection associated, atypical Doppler ultrasonography (suspected arterial, venous
Glomerulonephritis (GN) thrombosis)
Postinfectious GN Renal biopsy (specific diagnosis feasible)
Systemic disorders: SLE, Henoch-Schonlein syndrome,
microscopic polyangiitis includes measurement of blood pressure, search for signs
Membranoproliferative GN of congestive heart failure, fluid overload, acidosis and
Interstitial nephritis (drug-induced, idiopathic) anemia. Complications such as dehydration or fluid
Bilateral renal vessel occlusion (arterial, venous) overload, hypertension, heart fa ilure, severe anemia,
Postrenal failure
hyperkalemia and acidosis requ!re urgent treatment.
Posterior urethral valves, urethral stricture Fluid Repletion
Bilateral pelviureteric junction obstruction
Prerenal ARF responds to fluid replacement with
Ureteral obstruction (stenosis, stone, ureterocele)
improved renal perfusion and increased urine output.
·Neurogenic bladder
Dehydration is corrected by infusion of 20-30 ml/kg of
NSAIDs: Nonsteroidal anti-inflammatory drugs; SLE: Systemic lupus normal saline or Ringer's lac tate over 45-60 min. If
erythematosus hemorrhage accounts for vasc ular collapse, blood
transfusion should be given. Potassium should not be
nonresolving glomerulonephritis; (ii) AKI associated with administered until urine flow is established; care is taken
underlying systemic disorder, e.g. lupus erythemato~':1s, to avoid overhydration. Patients with renal hypoper-
Henoch-Schonlein purpura; (iii) suspected intershh~l fusion, in whom the only reason for oliguria is intra-
nephritis; (iv) clinical diagnosis of acute tubular necrosis vascular volume depletion, respond to fluids with increase
or HUS, if significant dysfunction persists beyond 2-3 in urine output (-2 ml/kg over 2-3 hours). Appropriate
weeks; (v) underlying cause of AKI ~ot ap~arent on fluid therapy should be continued. However, if no diuresis
clinical features and investigations. Patients with severe occurs despite correction of dehydration, frusemide
azotemia might require dialysis prio~ to biopsy to red':1ce (1-2 mg/kg IV) may be given. If these measures fail to
the risk of bleeding. Figure 17.16 indicates representative induce diuresis, a diagnosis of AKI is likely.
diagnoses on histology.
Occasionally, a patient with undetected chronic kidney Fluid Restriction
disease may present for the first time with acute onset of In patients with AKI, fluid retention may result from
oliguria. History of previous renal disease may be_p~:sent. excessive oral or parenteral fluids, and leads to edema,
The presence of the following suggests the ~oss1b1hty of hypertension and heart failure. Daily tluid requirement
chronic kidney disease: (i) retarded phys1c~l growth, is restricted to insensible water losses (300-!00 mL/ m 2),
(ii) severe anemia, (iii) hypertensiv e retmopathy, urine output and extrarenal fluid losses. This is usually
(iv) hypocalcemia, hyperphosphate~ia and high para- given orally; intravenous fluids are not required.
thormone, (v) r adiologic features of mineral bone disease Intake-output monitoring, daily weight, physical exami-
and (vi) small kidneys on imaging. nation and serum sodium guide fluid management. If fluid
in an appropriate volume and composition is given, the
Management patient should lose 0.5-1 % of weight every day a~1d se~u.m
Prompt clinical and laboratory evaluati?n is necess~ry. sodium should stay within normal range. A rapid weight •
Management includes treatment of hfe-threatemng loss and rising sodium suggest in adequate fluid
complications, maintenance of fluid and electrolyte_bal~ce replacement, while absence of weight loss and low serum
and nutritional support. Evaluation for complications sodium indicate fluid excess.
·.,
- ------ -··-
- 484
---~--~----------~------~E~s~s~e~n~ti~a~l~P!e~d~ia~tr~ic=s~~------------------------------
~
Fig. 17. 16: Photograph of kidney biopsy showing [a) Acute tubular necrosis/injury In the form of simplification of proximal 1ubulor
epithelium along with fine granular costs In some tubular lumlna [H & E 200 x ); (b) Patch of acute cortical necrosis Involving glomerull,
tubules and lnterstltlum with adjacent relatively preserved cortical porenchyrno (H & E 40x); (c) Throm botic m ic roanglopathy, suggested
by glomerull with marked endothelial swelling, capillary lumlna occluded by fibrin thrombi and mesanglolysls; [d) Tt1rombotlc
mlcroanglopothy, suggested by glomeruli showing endothelial swelling and detachment, widened subendothelial spaces. and
arterloles showing Intimal hyperplasia, endothelial swelling and lumen occluded by platelet thrombi (arrow)
I
Disorders of Kidney and Urinary Tract I 4ss •
Dopamine at low doses causes renal vasodilatation and interstitial nephritis is suspected, the offending agent
may induce a modest natriuresis and diuresis. However, should be withdrawn and oral corticosteroids given.
it has no ~enefici~l effect on the outcome of AKI, and may
be ass~ciated wit~ transient tachyarrhythmia or tissue Dlalysls
ischemia. Hence, its use for prevention or treatment of
AKI requiring dialysis can be managed with multiple
acute tubular necrosis is not recommended. The role of
modalities, including peritoneal dialysis, intermittent
othe~ medication~, including fenoldopam, atrial natriuretic
peptide and calcium channel blockers is investigational. hemodialysis and continuous hemofiltration or hemodia-
filtration. The purpose of dialysis is to remove endogenous
Treatment of Compl/catlons and exogenous toxins and maintain fluid, electrolyte and
acid-base balance until renal function recovers.
In a child with ARF, immediate attention is directed
towar~s ~etection and management of life-threatening
Indications for dialysis include persistent hyperkalemia
comphcattons. Table 17.17 lists important complications (>6.5 mEq/L), fluid overload (pulmonary edema, severe
and measures for their management. Children with hypertension), uremic encephalopathy, severe metabolic
pulmonary edema and congestive cardiac failure may acidosis (bicarbonate <10-12 mEq/L) and hyponatremia
require endotracheal intubation and assisted ventilation. (<120 mEq/L) or hypematremia. The decision to institute
Severe acidosis is treated by administration of sodium dialysis should be based on assessment of the patient and
bicarbonate, and, if persistent, dialysis. keeping in view the likely course of AKI. Dialysis should
Infections, including respiratory and urinary tract, begin early to prevent life-threatening complications.
peritonitis and septicemia, are important causes of death. The choice of dialysis modality is influenced by several
Procedures should be performed with aseptic techniques, factors, including goals of dialysis, the advantages and
IV lines carefully watched, skin puncture sites cleaned, disadvantages of each modality and institutional resources
and long-term catheterization of the bladder avoided. (Table 17.18).
Specific Therapy Peritoneal dialysis: Peritoneal dialysis does not require
Patients with atypical HUS benefit from plasma exchanges. vascular access and sophisticated equipment and is easy to
Immunosuppressive medications and plasma exchange perform even in neonates. It is often the initial renal
are useful in dialysis-dependent patients with vasculitis, replacement therapy of choice in sick and unstable infants.
crescentic GN or systemic lupus erythematosus. If Peritoneal access is obtained using a stiff catheter and trocar,
01· fl Bofl 1Jllllflllc catheter (oec Chnptcr 29). The abdominal The most important complication is peritonitis.
Rkfn lu pn!p1m•d m1 for u 1mrglc11I procedure. Dinlysia fluid Meticulous aseptic precautions will minimize its incidence.
ltt lnfUlll!d 30- [j() 1111,/ k14, fefl In the peritoneal cavity for 30- Stiff ca thcters should be removed after 48-72 hours, beyond
601111111111d fhe11 drained 1ml11g Hlphon effect (Pig. 17.17a). which the risk of infection is very high. The risk of injury
f11ftl11lly :30='1 11 <:yd,.H111·c c1mlcu oul. Commercially available to viscera and infections is considerably less with soft
dl11ly1111 lt•1111r1• lm:l;1h: b.wcd and wilh a dexlroi;e conccntrntion silastic (Tenckhoff or Cook) catheters, which, therefore, can
of ·1.7%. In pitllP11fM wllh fluid overloau, the concen tration be used for prolonged period s. Whi le the standard
of cl ex tnmc IH lncnwJt!d to 2.5-:1% lo frlcililn te u llrafiltra lion. (double-cuff) Tcnckhoff catheter needs to be placed
Puln11Hl11111 1111101 acldcJ in the firHl 5-10 cycles, lo enable surgically, a temporary (peel away) catheter is inserted
C01Tc<.:llo11 of l1ypcrknlcmla. Later, 3-4 mEq/ L potassium bedside. The use of an automated cycler is preferred to
chloride IH added lo lhc dl11 Iy1:111 le. The results of peritoneal manual peritoneal dialysis.
dlnlyHIHnm grnllfyl11g. l11 acute lubular necrosis, often a single
d lalyHIH111 nclcq11alc. The procedure can be repeated, if llcmodialysis: Hemodialysis is efficient for correction of
ncccmmry. fluid and electrolyte abnormalities. It is expensive to
Pure
water
~-
•c:r~ -==
Blood returned
.._ ii
Pottont __. : I
0 0
Blood removed l -t
: -~-..a
!
Dextr8se ()A A Blood
0 0 A pump Drain Fresh
oA () OA . __ _____ ___ • __________ __ ___ __ dialysate ,
Drolnooo L>og 0 . A
0 0 0 To&ns()
-- ---------------J
A
0 0 Water A b
a 0 0 (>A 0
A
Fig. 17. 17: Modolltlos ot dialysis tor acute kidney Injury. (a) Peritoneal dialysis Is based on solute sfer
across Iha porltonoar membrane, driven by the concentration gradient and high dextrose content of ~xc~~nge and water t~~~rysls
I roqulros blood to bo pumped outside the body via a large bore double lumen catheter followed
(Fig.17.17b). These dialyzers are available in different sii.cs (\'I) 1wphrntoxk lllt dk11llon:-i, 1~ .~. 111ni1111Hl)'l'llt1ldt1r.l,
1
(0.5-1:5 m 2) and sel~ction depends upon patient size nnd lndnnwtlrndn; m11lt rn1tl l11t11kt• 1,f :\l II l11hlhltol'H,
1
ultraftltrate properties. Vascular access is necessnrv for ninW!'l\llldt•; nnd (vii) n•1111I \'1•ln lhrn111\,wd~1, ''·!-\· In l11f1rnlr:1
removing and returning large quantities of blood reqi1ircd of diabetic; nwth1ir~, s1•\' 1~n· birth il~•l'hy ,,ln, d11hyd1't\tllln1
for the procedure. This is usunlly achieved using a double polycytlwmin nnd l'11tlwh•rlz11th1n nr umhllk11l vt•lnti. A1( 1
lumen catJ:eter in.serted into the internal jugular, femornl may 0crHslonnll~· bu llw flr:-it mr11\lfl':-1t11th1n of i\ l'llllHt.ll\lll\I
or subclavian vem. Most children are maintnined on a nnomal\' of th11 urlnnrv tl'llcl.
hemodialysis regimen of 3-4 hours, Unee times n week. l~en11·1 foilurn 1:-i i:;u;1wcll'd In th~ pr11 ~1 1 1w11 111' nll~11rl1'
Sick patients with fluid overload benefit from dnily (min' m1tput O.!l mL/kH/hr) OI' hlnod lTt111t lnln1l ~ I.:! tnK/
dialysis initially. dL. S~rum cr1•11tlnlnc~ le\'ds arn hlfih 11t birth (rdh•ctl11H
Co11ti11uous renal replacement t11era11ics (CRRT): CRRT is ma ten ml l11 vcls) 1md dl'Cn'i\Sl' lo b1•lo\\' ll.!\ I\\}\/ d L hy 'l- '7
any extracorporeal blood purificntion therapy inknded to dnys of n~1'. F111l\ll'l' llf 1wl11cllnn or rlst• 11f s1•r11m cn:11llnhm
substitute for impaired renal function O\'er an extended indicnles imp11h'l•d n•n,,l f11ndinn.
period of time and applied for, or aimed at being applied The principles nf nrnn l~t·nwnt "1'11 ~lmllilt' to llrnl f<H'
for, 24 hours a day. Various modalities include [continuous older ..:hildrl'n. Fluid should hl~ llmlh•d lo l11:i1'm1lhh'
arteriovenous hemofiltrntion (CAVH)], [continuous (30 mL/k~ / d,,y for full-ll'l'm, ."ll- tlll) ml./ k~/ d1l)' flll'
venovenous hemofiltration (CVVH)]. continuous vcno- pre h. rm tWlllUttes), ~nstrnint1•slin 11I .ind r0n11I l11~~~11•1t.
1
venous hemodiafiltration (CVVHDF) and slow continuous Exlremdy pn'm.1lurc 1wnnnll'S l\\ll'St'd In r1Hll1rnl \Vlll'llll'l'ri
ultrafiltration (SCUF). These U1erapies are useful when large require c'l:tl'll fluids. S)•sltllil' blnnd pn'sSlll'l' 111111\• tlm11
amount of fluids have to be removed in sick and unstable 95-lOO mm H~ mny 1w1•d lt'l'nlnwnt.
patients. CVVH is preferred modality in AKI secondary to Extt-.1 C'lll'l' shnuld ht~ lnken whil1• di11ly:t.inK IH't)IH\li'~;
major surgical procedures, bums, heart fa ilure anct septic perito1w.1l dialysis is lt'drnirnlly t'11sh•r 1md pr,•h_•1·rt•d.
shock, especially when conventional hemodialysis or Howe\'l'r, smhh•n disll'nlion tl f 1wrltrnw.d 1\\\'lly mny
intermittent peritoneal dialysis is not possible. cnusc respi1-.lltH'Y l'mh1H'l'1lssnwnl 1ll' np1wn. I lypntlwrmll\
should be avoidt'd by c.ucfully w:mning tlw dl11l~·sls fluid.
Slow lo11g extended daily dialysis (SLEDD): Sick patients A number of drngs i:u e dinly:1.11blt• and nppl'(1p1'111h1
often benefit from hvbrid treatments that combine the amounts should be nddcd In supplement for th •Ir lV!l~lt'll.
advantages of CRRT ~d feasibility of hemodialysis. SLEDD
is done daily for an extended but limited period (8-10 hours) Suggested Reading
using low dialysate flow rates and at the same time • Ckci,, E, Dl!\'<1r11jnn I'. P1~di11lrlr 1w11h• l..ld1wy inlury: pr1·\'11h·111:1•,
minimizing the cost and technical complexities of CRRT. impilct <md """'·'~1•m1•nl ch.1 ltt-11~1·:1. Int j N1•plm1l l~1'111w,1•11: Di~
2017; IO:i7-lt
Outcome • }l'ttnn JG, J\ ~l..1• 1'111.i DJ. Updnl1' 1111 1\c\111' kld1w\• lnj11rv In llw
m•1l1Mt1'. Curr Opln l\•dl.1lr 2012; 2·1:191- ti. · ·
AKI carries a mortality of 20-40%, chiefly related to the
• !Vlooru PK, I l~u RK, Liu KO. l\l,1n.1}\l'l\l1'1\I nf <h'lll1• l..hliwy lnjury:
underlying etiology and duration of renal failure. P~tients Cnrc ('mrinilum WIH. i\m J Kid1wy rn~ ~\l\li; 72: 1- 1:1.
with septicemia and HUS with prolonged anuna are • Ricci Z, G1,hlst1•i11 SI.. l\•di.1trk n'nlhn111w; l"l'llnl n•plt1l'••11wnl
associated with poor prognosis. The outcome in crescentic tht-rnpy. Conlrib Nq,hrnl 201 <•; 1~7: 1:?1 -.1ll,
GN and vasculitis depends on the severity of the renal • S1'lcwski DT, C.lildstl'ln SL. Tlw 1·1111• nf fluid 1)\•1•rlond 111 tlw
injury and promptness in initiation of specific U1ernp~. pn•dlclion or lllltC'llllW in <lCllll~ khhwy injury. l\·dlntr Nl'phml. :'.ll IH;
33:13-24.
The outlook is satisfactory in acute tubular necrosis
Without complicating factors. Other factors associated
HEMOLYTIC UREMIC SYNDROME
With poor outcome include delayed referral, presence of - -
complicating infections and cardiac, hepatic or rcspi.ratory Hemolytic url'mk syndrome is n hl'lt!rog1'1w111111 grm1p of
failure. Maintenance of nutrition and prevention of disorders that arc n common cnusc nf AKI In children.
infections is crucial in improving outcome. They arc chnradcri zcd by micrnnngiopnlhk lwrnnlytk
chlldrcm of nil ages and Is flssocinted with abnormalities (Figs 17.16c and d). The capillary lumen is narrowed b
of thu nlLcrnnllvc complement pnthway (complement swollen endothelial cells, blood cells and fibrin thromby
M1Aoclotccl or atypical HUS). Arterioles may show similar changes. Patchy or extensivi.
renal cortical necrosis may be present. HUS is diagnose~
Shlgatoxln·Assoclated HUS on clinical and laboratory features, and a renal biopsy is rarely
Verotoxln-produclng E. coli (in North America and required.
U11ropc; mrn1t commonly 0157: H7; 0104:H4 in a recent
Treatment
epidemic) nnd Shigclln dyscnlcrine 1 (in south Asia) cause
1'110 dlnrrhcnl prodron1c preceding HUS. Cytotoxin- Treatment includes management of complications of renat
mcdlntcd injury to endothelium in the renal micro- failure, treatment of hypertension and correction of
vnsculnturc lcndf! to localized congulation and fibrin anemia. Proper nutrition must be ensured. Peritoneal or
deposition. As red cells and platelets traverse these hemodialysis may be necessary to prevent complications
dnmngcd vessels, they arc injured and sequestered. of renal insufficiency. Repeated plasma exchange with
Though the brunt of the microvascular injury is on the infusion of fresh frozen plasma is recommended for
kidney, other organs especially the brain may be affected. patients with atypical HUS. Plasma exchanges are initiated
Slncl! chiefly shigntoxins 1and2 are implicated, the illness as early as possible, performed daily until hematological
ls nlso coiled shigntoxin E. coli-related hemolytic uremic remission, and then less frequently. Patients with anti-
Ayndromc (STEC-HUS). factor H antibodies benefit from immunosuppression with
agents that reduce antibody production. The use of
Atypical HUS eculizumab, a high affinity monoclonal antibody targeted
against CS, benefits patients with HUS associated with
This condition often lacks the prodromal history of
activation of the complement cascade. While effective in
dinrrl~ca or dysentery, but may be triggered by minor
ensuring hematological and renal remission, the
Infections. The onset may be insidious or present with a
medication is not available in the country.
rnpidly progressive illness. Microangiopathic lesions
chiefly affect interlobular arteries and result in severe Outcome
hypertension and progressive renal insufficiency.
Predisposing factors include mutations in regulators of Mortality during the acute episode of shigatoxin
the complement pathway (factors H, I and B, C3, associated HUS is low. On follow-up, 20-30% patients
membrane cofactor protein and thrombomodulin), and show v~rying degree of residual renal damage. Factors
antibodies ngainst complement factor H. suggestive of poor outcome include oligoanuria for more
than 2 weeks, severe neurological involvement and
Cllnlcal and Laboratory Features presence of cortical necrosis. The acute and Ion<T·term
outcome. in aty~ical HUS is unsatisfactory, thou~h the
Children of all ages may be affected. Following a
prognosis h~s improved with supportive measures.
prodrome of acute diarrhea, dysentery or a febrile illness,
Recurrent episodes of HUS may occur, including in the
patients show sudden onset of pallor and oliguria. Blood allograft after renal transplantation.
pressure may be high. Focal or generalized seizures and
alteration of consciousness are common. Many patients Suggested Reading
do not show a prodromal illness.
The blood film shows broken and distorted red cells, • Ariceta G, Be~ba~ N, Johnson S, European Pediatric Study Group
f~r HUS: Gmd.ehne for the investigation and initial therapy of
increased reticulocyte count and high blood levels of LOH. diarrhea negative hemolytic uremic syndrome. Pediatr Nephrol
Coombs' test is usually negative except in S. pneumoniae 2009, 24:687-96.
associated HUS where the test is positive. Thrombo- • Fakhouri F, Zuber J, Premeaux-Bacchi V, Loirat C. Haemolytic
cytopenia is usually present; neutrophilic leukocytosis is ur~emic sri;drome. Lancet. 2017; 390(10095):681--696.
• Louat C, Premeaux-Bacchi V. Atypical hemolytic uremic syndrome.
seen in patients with shigellosis. Urine shows microscopic · Orphanet J Rare Dis 2011; 8:6--60.
hematuria and mild proteinuria. Blood levels of urea and • Walsh PR, Johnson S. Treatment and management of children with
creatinine reflect the severity of renal failure. In patients haemolytic uraemic syndrome. Arch Dis Child 2017· doi: 10.1136/
with STEC-HUS, establishing etiology requires either stool archdischild-2016; 311- 377. '
culture or PCR for STEC or ELISA for shigatoxin. Serum
complement C3 levels are low in some patients with CHRONIC KIDNEY DISEASE
atypical HUS. Detailed analysis of components of the Chronic kidney disease (CKD) is defined as kidney
alternative complement pathway and its regulators is damage lasting for at least 3 months as characterized by
recommended in all patients with atypical HUS. structural or functional abnormaliti~s of the kidney with
I
On renal biopsy, the endothelial cells are swollen and or without decreased glomerular filtration rate (GFR)·
separated from the basement membrane with accu- Abnormalities may include structural malformations (e.g·
mulation of foamy material in the subendothelial space hydronephrosis, single kidney), pathological conditi0115
Disorders of Kidney and Urinary Tract 489 I
r- -.......-----~-
(e.g. focal segmental glomerulosclerosis) and markers of frequent passage of urine, nocturia and increased thirst.
kidney damage such as abnormal urinalysis (hematuria, Anemia that is usually normocytic and normochromic is
proteinuria) or biochemistry (persistently increased serum chiefly due to reduced renal erythropoietin production.
creatinine). CKD is divided into 5 stages, based on level Mild hemolysis and blood loss from gastrointestinal tract
of GFR estimated from level of serum creatinine and height may also contribute.
using the modified Schwartz formula (Table 17.19). Since Resistance to the action of growth hormone, the levels
renal maturation increases from infancy to reach adult of which are increased, is considered to be responsible
values at the age of 2 years, CKD stages apply only to for growth failure. Anorexia, malnutrition and skeletal
children beyond >2-year-old. Terms such as chronic renal deformities contribute to growth retardation. Abnormalities
failure and end stage renal disease are avoided. Important in metabolism of calcium and phosphate and bone disease
conditions resulting in CKD are listed in Table 17.20. results from hyperphosphatemia, lack of renal formation
Congenital abnormalities of the kidney and urinary tract of 1, 25-dihydroxyvitamin 0 3 , deficiency of calcium,
(CAKUT) are the leading causes of CKD in childhood. chronic acidosis and secondary hyperparathyroidism.
The blood pressure may be increased and optic fundi
Pathophyslology and Cllnlcal Features show hypertensive retinopathy. Severe proximal muscle
The term CKD implies permanent decrease in renal weakness, peripheral neuropathy, itching, purpura and
function. Most children with CKD stage 1-3 (GFR more pericarditis are late features . Infections are common and
than 30 mL/rnin/1.73 m 2) are asymptomatic; reduction may acutely worsen renal function.
of GFR below this level is associated with symptoms.
Regardless of the etiologtj, once there is a critic~l loss of ne~h~on Investigations
mass, the renal failure is progressive and 1}1anife~t~ wzth s1m1l~r The patient should be investigated to find the cause of
symptoms. Loss of urinary concentrating ability results m renal failure and detect reversible factors (e.g. urinary tract
obstruction, UTI, severe hypertension, drug toxicity and
fT abie -17.20: Commo'n causes of chronic kidney disease I dehydration). Appropriate imaging studies are done.
G!~merulonephritis: ldi~pathic (e.g. focal segmental glomerulo- Blood counts and levels of urea, creatinine, electrolytes,
sclerosis); secondary (systemic lupus erythematosu~, lg.A pH, bicarbonate, calcium, phosphate, alkaline phos-
nephropathy, microscopic polyarteritis, Henoch-Schonlein phatase, parathormone (PTH), protein and albumin are
Purpura) obtained. Levels of ferritin and transferrin saturation are
obtained in patients with anemia. GFR can be estimated
Reflux nephropathy: Primary, secondary
based on serum creatinine and height (p 465); its accurate
·obstructive uropathy: Posterior urethral valves, pelviureteric
assessment by creatinine clearance or radionuclide
junction obstruction, renal stones
methods is rarely necessary.
Developmental anomalies: Bilateral renal hypoplasia, dysplasia
Familial nephropathy: Nephronophthisis, Alport syndrome,
Polycystic kidneys .
Others: Hemolytic uremic syndrome, amyloidosis, renal vein
thrombosis, renal cortical necrosis .
Management
Optimal management of CKD involves a team approach
involving pediatric nephrologist, specialist nurse,
dietitian, social worker and orthopedic surgeon. The
I
management of CKD focuses on the following pri~ciples: sodium requiring its sui:'~leme~tation: Children with
(i) Treatment of reversible conditions; (ii) Retarding the chronic glomerulonephntis r~tam sodmm. and water,
progression of kidney disease, with particular attention which contributes to hypertension. These patients require
to control of hypertension and proteinuria; (iii) Anticipa- salt and water restriction and may benefit from diuretics.
tion and prevention of complications of CKD; (iv) Optimal Potassium: Renal regulation of potassium balance is
management of complications, including anemia, mineral maintained until very late, but the capacity to rapidly
bone disease, malnutrition, growth failure and metabolic excrete a potassium load is reduced. Dietary items with
acidosis; and (v) Identification of children in whom renal large potassium content should be avoided.
replacement therapy (RRT) is anticipated; adequate
counseling and preparation of the family for RRT. Calcium and phosphonis: Calcium supplements are given
At the initial stages, management aims at maintaining as calcium carbonate or acetate. Excessive consumption
nutrition and retarding progression of the renal failure. of dairy products should be avoided to restrict phosphate
Later, treatment of complications and renal replacement intake.
therapy in the form of dialysis or transplantation is required.
Vitamins: Vitamins B1, B21 folic acid, pyridoxine and B12
Treatment of Reversible Renal Dysfunction are supplemented.
Common conditions with potentially recoverable kidney
function include an obstruction to the drainage, recurrent Hypertension
urinary tract infections with vesicoureteric reflux and Hypertension in patients with proteinuria and glomerular
decreased renal perfusion due to renal arterial stenosis. filtration rate >30 mL/min/1.73 m 2 should preferably be
Care should be taken to avoid AKI that may follow the treated with angiotensin-converting enzyme inhibitors
administration of nephrotoxic drugs, herbal medications (e.g. enalapril). Beta-adrenergic blockers (atenolol) and
and radiocontrast agents, and occur with hypoxic injury calcium channel antagonists (nifedipine, amlodipine) are
due to inadequate hydration during or following surgery. also effective; the latter are the preferred initial choice in
Retarding Progression of Renal Failure CKD stage 4-5 (GFR <30 mL/min/ 1.73 m 2 ). Treatment
with loop diuretics is beneficial in those with fluid
Hypertension and proteinuria lead to increased intra- overload. Patients with severe hypertension, uncontrolled
glomerular perfusion, adaptive hyperfiltration and pro- with the above medications, may require additional
gressive renal injury. Hypertension should be adequately therapy with clonidine or prazosin.
controlled. Long-term therapy with angiotensin-
converting enzyme inhibitors has been shown to reduce Anemia
proteinuria and may retard progression of renal failure.
Anemia generally develops when the GFR falls below
Strict control of blood pressure to 50th to 75th centile for
30 mL/min/1.73 m 2 • Iron deficiency, indicated by low
age, gender and height, is useful in delaying progression.
levels of transferrin saturation (<20%) and fe rritin
Children with proteinuria should be treated with an ACE
(<10~ ng/ dL), is the most common un d erl ying
inhibitor or an angiotension receptor blocker (ARB)
contnbutmg factor. Therapy with iron (elemen:al iron
because of their antiproteinuric effect. Therapy with lipid
4-6 mg/kg per day) should be initiated in such cc1ses. Iron
lowering agents and correction of anemia, shown to be
replete patients with pernicious anemia should 1eceive
useful in retarding progression of CKD in adults, may also
have utility in children. therapy with rec~mbinant human erythr ~)poietin
50-1~0 U /kg/ dose given subcutaneously or inh·a,·enously
Diet 2-3 hmes a week. The dose of erythropoietin should be
Careful attention to diet is essential. Recommended daily adj~sted to achieve .target hemoglobin of 11-12 g/dL.
amounts of calories should be ensured. A diet high in Patients should receive iron and micronuh·ient supple·
polyunsaturated fats, such as corn oil and medium chain men.ts c?ncomitantly: Patients on hemodialysis should
triglycerides and complex carbohydrates is preferred. receive intravenous iron supplementation. Inadequate
Water restriction is usually not necessary, except in ESRD response to erythropoietin may occur due to iron, folate
or presence of fluid overload. Excessive use of diuretics, or vitamin B12 deficiency, chronic infection, aluminurn
overzealous restriction of salt and gastroenteritis may lead toxicity and severe hyperparathyroidism. Patients with
to dehydration that should be corrected. hemoglobin level below 6 g/ dL should receive leukocyte·
poor, packed red cell transfusions. Blood is transfused slowly,
Proteins: The protein intake should be 1-2 g/kg/day; since it may aggravate hypertension and heart failure.
proteins consumed should be of high biologic value.
Restriction of protein intake is not required. Infections
Sodium: Since renal regulation of sodium reabsorption is Urinary tract and other infections should be promptly
impaired, its dietary intake needs to be individualized. treated with effective and least toxic drugs. The dosage of
Some infants are polyuric and lose large amounts of most drugs requires modification (reduction of dosage
Disorders of Kidney and Urinary Tract I 491 -
and/ or increase in dosing interval), depending on the hypocalcemia, hyperphosphatemia and raised levels of
severity of renal failure. alkaline phosphatase and PTH. X-rays reveal changes
suggestive of rickets. Radiologic features of secondary
Growth hyperparathyroidism are initially seen in the phalanges
Optimization of caloric and protein intake and treatment and clavicles.
of mineral bone disease is important. Administration of The goals of early intervention are to maintain normal
recombinant human growth hormone at 0.024-0.070 mg/ bone mineralization and growth, avoid hyperphospha-
kg subcutaneously once a day, 6-7 times a week (max 0.35 ternia and hypocalcernia, and prevent or reverse increased
mg/k?/week) ~proves growth velocity in children with PTH secretion. Treatment is based on dietary restriction of
chrome re":a~ failur.e. Early recognition and management phosphate, and administration of phosphate binders and
of malnutrition, mineral bone disease, metabolic acidosis vitamin 0. When serum phosphate exceeds the target
and. el~o~yte disturbances should take precedence over range, phosphate containing food (e.g. dairy products) are
the mstitutio.n of ther~py with growth hormone. The goal restricted. Oral phosphate binders, calcium carbonate or
of the~apy is to achieve the patient's genetic height acetate (0.5-1 g/ day with meals) reduce intestinal
potential. absorption of dietary phosphate. Since aluminum
accumulation may increase the risk of bone disease and
Mineral Bone Disease encephalopathy, prolonged administration of aluminum
Mineral bone disease (MBO) is a serious problem in hydroxide as a phosphate binder is avoided. Sevelamer, a
children as it occurs during the period of active growth calcium and aluminum free ion-exchange resin that binds
(Fig. 17.18). Its prevention and adequate treatment is phosphorus within the intestinal lumen, is a safe and
crucial. The proximal nephron is the chief site of synthesis effective alternative to calcium containing phosphate
of 1,25-dihydroxyvitamin 0 3 (cakitriol), the most potent binders.
metabolite of vitamin 0. Its decreased production is an The first steps in managing elevated levels of PTH in
important factor in the pathogenesis of secondary children with CKO are correction of underlying
hyperparathyroidism in CKO. Recent studies also show a nutritional deficiency of vitamin 0 deficiency and
high incidence of vitamin 0 deficiency among children management of hyperphosphatemia. If the PTH still
with CKO. With reduction of renal function, phosphate remains elevated after these measures, therapy with
balance is initially maintained by its increased excretion activated vitamin 0 should be started. Vitamin D analogs
from the normal nephrons. However, when the GFR falls with short half-life (calcitriol, 20-50 ng/kg/ day or lcx-
below 25%, blood phosphate levels rise. hydroxy 0 3 , 25-50 ng/kg/ day) are preferred. Excessive
The symptoms of are vague and nonspecific. Bone pain, vitamin D intake may cause hypercalcemia, hyper-
muscle weakness, growth retardation and skeletal calciuria and elevation of calcium phosphorus product,
deformities are prominent. Blood examination shows which should be monitored.
Osteotomy may be required to correct bony deformities.
Immunization
Patients with CKO should receive all routine vaccines.
Apart from the regular immunization, children with CKO
should also receive vaccines against pneumococcal,
chickenpox and hepatitis A and B infections, especially if
prepared for transplantation. Immunization is scheduled
so as to complete live vaccinations prior to transplantation.
Primary as well as booster doses of inactivated vaccines
can be given 6 months after transplant.
Long-term Care
The rate of progression of chronic renal injury is variable.
In some disorders (e.g. hemolytic uremic syndrome,
crescentic GN), stage V CKO is present within a few weeks
or months. In others (e.g. reflux nephropathy and some
I
Chronic Hemodlalysls (HD)
are less common. Early and correct diagnosis is essential
HD is mostly carried out in the hospital setting. These since specific management is possible in many cases. The
children require vascular access either an arteriovenous diagnosis of a primary tubular disorder implies that there
Disorders of Kidney and Urinary Tract 1493 -
,,.---
iS no significant impairment of glomerular function or Table 11.21~esenting f;!atures in tubular disorders
tubulointerstitial inflammation. A tubular disorder may be Growth retardation, failure to thrive
congenital or acquired and involve a single function of a Delayed gross motor milestones
tubule (renal glucosuria, nephrogenic diabetes insipidus)
Polyuria, excessive thirst
or multiple functions (Fanconi syndrome).
Recurrent episodes of dehydration, vomiting, fever
Initial Evaluation . Rickets, bone pains
Children with primary defects in tubular function usually Episodic weakness
present during infancy. Table 17.21. shows important Constipation
clinical features of patients with such disorders. Most renal Craving for salt and savory foods
tubular disorders can be diagnosed following careful
interpretation of urine and plasma biochemistry, key glomerular filtration rate. Patients with distal RTA are
investigations are listed in Table 17.1. unable to excrete ammonium (NH;) ions adequately, a.nd
the urine pH cannot reach maximal acidity (i.e. rema.ms
Renal Tubular Acidosis (RTA)
>5.5) despite acidemia, indicating ~ow H+ conc.e ntrahon
RTA encompasses conditions characterized by a defect of in the collecting duct. Hypokalemia is caused by .rncrea: ed
renal acidification, which result in h yperchloremic urinary losses of potassium and aldosterone stimula tion
metabolic acidosis and inappropriately high urine pH. by urinary Na+ loss and volume co~traction, leading to
Defects in tubular transport result in reduced proximal further increase in tubular K+ secretion.
tubular reabsorption of bicarbonate (HC03), the distal The condition is often sporadic, but may be inherited
secretion of protons (hydrogen ion, H+) or both, leading (dominant, recessive or X-linked). Important .forms ~re
to impaired capacity for net acid excretion and persistent listed in Table 17.22. The disease may be associated with
hyperchloremic metabolic acidosis . The plasma anion gap systemic diseases (systemic lupus er~thematosus, wn:on
[Na+-(CI- + HC03)] is in the normal range (B-12 mEq/L). disease) or seconda ry to r enal disease (obstructive
The renal function is normal or only mildly impaired. uropathy, reflux nephropathy) or drug toxicity (lithium,
Two main forms are recognized : Distal RTA (type 1) analgesics, amphotericin B).
and proximal RTA (type 2). Another variety (type 4) distin-
guished by the presence of hypoaldosteronism and Presenting f eatures: Children present with failure to thrive,
hyperkalemia is less common in children. polyuria, polydipsia, hypokalemic muscle weakne~s an_d
rickets. Ultrasonography may show nephrocakmosis
Distal RTA (Fig. 17.20).PatientswithincompleteforrnsofdistalRTA may
Distal (type 1) RTA is due to defec~ve .s~cretion of H+ ~ present with nephrolithiasis or incidentally detected
the distal tubule, in the absence of sigruficant decrease m nephrocalcinosis.
r:.
~ Typ~ of RTA
Table 17.22: Inherited forms of renal tubular acidosis (RTA)
Associated disorders
Hemolytic anemia
, Type 1 (distal)
Early hearing loss
Normal hearing; delayed hearing loss
Ocular abnormalities (band keratopathy, cataracts, glaucoma); defective
Type 2 (proximal), isolated
dental enamel; intellectual impairment; basal ganglia calcification
Dent disease
Type 2, Fanconi syndrome
Cystinosis
Tyrosinemia type 1
Fanconi-Bickel syndrome
Wilson disease
Galactosemia
Hereditary fructose intolerance
Lowe syndrome
Glycogen storage disease type I
Mitochondrial disorders
Osteopetrosis; blindness, deafness
Type 3 (combined)
Congenital adrenal hyperplasia
Type 4 (hyperkalemic)
Pseudohypoaldosteronism (PHA)
PHA type 2, Gordon syndrome
- 494 I Essential Pediatrics
I
Absent
Bone disease Common Often present Absent
U·B PC02: Urine to blood PC02 gradient
Disorders of Kidney and Urinary Tract 1495 -
~::.:~=-=O_Ll_TH_IA_S_l_
S ..;_AN::...::::D~N~E~P!!H~RO~C~A~l~C~IN~O~S~IS~-- should include renal function tests, blood levels of cal-
Renal calc~i are unconunon in children and occur usually cium, phosphorus, uric acid, pH and bicarbonate. Detec-
iJl the se~g of an underlying metabolic abnormality. tion of specific crystals in the urine may suggest an
symptoms_ mcl~de d!'suria, hypogastric pain, hematuria etiology (Fig. 17.22). High (>5.5) urine pH in first morning
and occaswna . Y urinary infections. Nephrocalcinosis sample suggests defccti\·e tubular acidification.
refers to formation of _crystalline deposits within the renal Quantitation of calcium, oxalate and uric acid in timed
parenchyma, presenting as enhanced renal echocrenicity urine collections evaluates excretion of solutes as com-
,.,,hich may be cortical, medullary or diffuse. Table 17.2.1 pared to normal indi\"iduals. Alternatively, solute excre-
lists c~mmon ~derlying metabolic causes. Urinary tract tion is expressed as a ratio to urinary creatinine in spot
infection, particularly with urease producino- orcranisms samples. Patients with hypercakiuria require e\·aluation
like Proteus, favors precipitation of magnesiun~an~1 oruun1 for hypercalcemia (intact PTH, 25-hydroxyvitamin D) and
phosph~te and c_alciu_m phosphate (struvite stones). for association with incomplete distal rena l tubular
Progress1v: ren_al rmpa1rment may occur in patients ,...,ith acidosis, hypomagnesemia, hypophosphatemic rickets
nephrocalonos1s, untreated obstruction or recurrent UTI. and abnormalities of the thyroid hormone . Where
available, stone analysis is performed u sing X-ray diffrac-
Evaluation tion or infrared spectroscopy.
Ultrasonography detects most radiopaque and radiolucent
calculi and nephrocalcinosis. High resolution computerized Idiopathic Hypercalclurla
tomography detects even minute calculi. Plain radio- This is the most co111111011 1111dt.'Tlyi11g rn11sc in patients with
graphs an~ intravenous pyelography are rarely required; nephrolithiasis, but may alternatively present with
the latter is useful only if suspecting radiolucent or low microscopic and gross h ematuria. A family history of
density stones {uric acid, xathine), duplex system or hemah1ria or nephrolithiasis is often present. Urinary
obstruction, particularly in a young child where perfor- calcium to creatinine ratio in the early morning 'spot' urine
ming CT would necessitate sedation. Howev er, high serves as a screening test. The upper limit of normal in
resolution ultrasonography may overdiagnose nephro- children over 2 years is 0.2 (mg/mg). The diagnosis is
calcinosis, particularly in newborns .w here physiologically confirmed by an accurate measurement of 2-1 hours
increased echogenicity or deposition of Tamm-Horsfall urinary calcium; values greater than -1 mg/ kg / day are
protein is mistaken for medullary nephrocalcinosis. abnormal. Blood levels of calci111111111d 111a~11t·s i1111111re 11om111/.
Investigations aiming at detecting abnormalities show Idiopathic hypercalcit~ria should be distinguished from
a metabolic cause in 50% patients. Initial investigations hypercalciuria secondary to persistent hypercalcemia (e.g.
hyperparathyroidism, v itamin D toxicity) or associated
- - . - with renal tubular acidosis. A high fluid intake and diet
Table 17.24: Underlying metabolic abnormalities in children
with nephrolithiasis or nephrocalcinosis low in animal protein and salt is advised. Therapy with
. . thiazide diuretics, which reduces urinary calcium
: Hypercalciuria with hypercalcemia
excretion, may be required.
Vitamin D overdose
Primary hyperparathyroidism Endemic Vesical Calculi
Production of PTH related peptide (malignancy, sarcoidosis)
Vesical calculi are usually single stones, detected in yotmg
Hypercatciuria with normal serum calcium
boys (<5-year-old) in some regions of the countn·, e.g.
Idiopathic hypercalciuria Rajasthan, Andhra Pradesh and NorU1-Eastern st,1t~s, and
Familial hypophosphatemia with hypercalciuria in neighboring countries, e.g. Pakistan and Afghanistan.
·Distal renal tubular acidosis These stones are composed of ammonium acid urate and
Dent disease calcium oxalate. Risk factors include consumption of a
Bartter syndrome with/without sensorineural deafness predominantly cereal (wheat or jowar) based diet, which
Autosomal dominant hypocalcemia with hypercalciuria has low amounts of calcium and phosphate and high
.Familial hypomagnesemia, hypercalciuria and nephro- oxalate content. Recurrent diarrheal episodes contribute
calcinosis by causing dehydration and an acidic, concentrated urine.
Lowe syndrome A high intake of dairy products and animal proteins has
Frusemide use led to a decline in the prevalence of U1ese stones.Treatment
Mlscellaneous causes requires suprapubic cystolithotomy; these stones rarely
Pn~arY hyperoxaluria (type I, type 11) recur.
Cystinuria
.Abnormal purine, pyrimidine meta?oli~m : Lesch-Nyhan Primary Hyperoxaluria
syndrome, glycogenosis type 1, xanthmuna Primary hyperoxaluria type 1 is an autosomal recessive
Melamine toxicity disorder of glyoxylate metabolism with deficient activity
- 498 Essenttal Pediatrics
•.
·~
"
.\:...
0, .
.. '}
'"t'' I
.;~ ,;
.. ·~ •l;.
'
-~
\ ..1 ~
' tr
.... '-> ..
a . . . . . __ _..___t·..~~·.._....~-·. . . . -~~~~ lP.~··~-'~·~·~
·.: , 1.) • "
__.
. ... ...·
I\;
.,
~
••
;::.:::::::::::::::;..;_.~~~~~~~--.
.. •. '
: . t... c .
. •
•
~
'l • '
'
:
. ':'
.. •
~~·
Fig. 17.22: Morphology of urlne crystals may suggest etiology of renal stones. (a) Envelope-shaped oxalate dihydrate crystals;
(b) Florets of calcium phosphate; (c) Coffin lid-shaped triple phosphate; (d) Hexagonal cystlne crystals
of the liver-specific enzyme, alanine glyoxylate amino- disulfide bonds of cystine to form the more soluble
trans ferase causing overproduction of endogenous homodimer, cysteine.
oxalate, which manifests as renal s tones and/ or
nephrocalcinosis. Precipitation of oxalate also affects the Management of Renal Calculi
eyes, heart, bones and bone marrow. The diagnosis is
suggested by elevated oxalate in plasma and/or urine, Stones less than 5-7 mm in size may pass spontaneously.
and confirmed by deficient activity of the enzyme on liver Extracorporeal shock wave lithotripsy (ESW L) may
biopsy and sequencing of the affected gene, AGXT. suffice for small stones. Percutaneous nephrolithotomy
Treatment is supportive; some patients with partial may be appropriate in patients with relative contra·
deficiency benefit from pyridoxine supplementation. indication for ESWL or with stones too large for
Patients presenting in childhood progress to end-stage lithotripsy. Ureteroscopy is useful for distal and mid·
renal disease by adolescence and require combined liver ureteric calculi. Open surgery is necessary for stones
kidney transplantation. more than 3 cm in size or those with associa ted
pelviureteric junction obstruction.
UTI should be treated and an adequate fluid intake
Cystlnurla ensured. Patients with idiopathic hypercalciuria may
This autosomal recessive disorder is characterized by benefit from a low salt intake; d ietary calcium restriction
impaired proximal tubular reabsorption of cystine and is not necessary. Persistent hypercalciuria is treated with
dibasic amino acids (ornithine, lysine and arginine). oral potassium citrate, an inhibitor of crystallization-
Supersaturation of urine with cystine crystals may lead Thiazide diuretics reduce urine calcium excretion; their
to formation of recurrent radiopaque calculi and account long-term use is, however, restricted due to side effects.
for 10% of cases presenting in childhood. The diagnosis is Prolonged alkali supplementation is necessary in patients
suggested by presence of hexagonal crystals in urine, with distal RTA.
urinary excretion of specific amino acids (as above) and
positive urine nitroprusside cyanide test. Confirmation Suggested Reading
requires quantification of urinary cystine excretion (24 hr • Copelovitch L. Urolithiasis in children: medical approach. Pediatr
or cystine:creatinine ratio), stone analysis or genetic Clin North Am 2012;59:881-96.
• Rumsby G. Genetic defects underlying renal stone disease. Ini J
testing. A high fluid intake and urinary alkalization help,
Surg. 2016;36(Pt D): 590-595. .
since cystine is poorly soluble at normal urina~y. pH ~ut
.....
- 500 Essential Pediatrics
postvoid residual urine or dysfunctional voiding. Cardiac Multicystic dysplastic kidney: A multicystic dysplastj
arrhythmias are a rare but serious adverse event effect of kidney (MCDK) is an enlarged nonfunctioning kidne c
tricyclic antidepressants, which are, therefore, not with cysts of varying sizes resulting f~om ~bnorrnfi
recommended. Anticholinergic drugs reduce uninhibited differentiation of the metanephros. Affecting 1 m 2400 to
bladder contractions and are useful in children who have 4300 live births, it is the most common cystic renal
significant daytime urge incontinence besides nocturnal malformation in children. Ultrasonography shows
enuresis. The usual dose is 5 mg for oxybutynin or 2 mg characteristic findings, including multiple thin-walled
for tolterodine at bedtime, given above 6 years of age. noncommunicating cysts of varying size, in an enlarged
Desmopressin (DDAVP, 0.2-0.4 mg orally; oral melt kidney without identifiable parenchyma or renal pelvis
120-240 µg) works by reducing the volume of urine. Its (Fig. 17.23).
rapid onset of action makes it a satisfactory choice for Most patients with MCDK have a normal contralateral
special occasions like staying out for the night. Relapse kidney showing compensatory hypertrophy. However,
rates are high after stopping the medication. 20-40% cases may show associated abnormalities of the
contralateral genitourinary tract, such as vesicoureteric
Suggested Reading reflux or pelviureteric junction obstruction. A DMSA scan
• Thurber S. Childhood enuresis: Current diagnostic formulations, confirms that the affected kidney is nonfunctional and
salient findigns, and effective treatment modalities. Arch Psychiatr rules out reflux-associated scarring of the contralateral
Nurs 2017;31:319-23.
• Van Herzeele C, Walle JV, Dhondt K, Juul KV. Recent advances in
kidney. Children with MCDK require regular monitoring
managing and understanding enuresis. FlOOORes. 2017;6;1881. by ultrasound to ensure compensatory hypertrophy of the
normal kidney and progressive involution of the affected
CONGENITAL ABNORMALITIES OF kidney, which is undetectable by 5-7 years of age in most
KIDNEY AND URINARY TRACT cases. Progressive renal impairment is seen, only if other
abnormalities are associated. The risk of malignant
Congenital abnormalities of kidney and urinary tract transformation (Wilms' tumor) and hypertension is
(CAKUT) are common and account for about 25% cases negligible. Nephrectomy is not indicated except in
of CKD in children. presence of severe hypertension, suspected malignancy,
or a large kidney that fails to involute.
Single Kidney
In unilateral renal agenesis, one kidney fails to form while Obstructive Uropathy
the other is normal in size, position and function. Agenesis Obstructive anomalies of the urinary tract are an important
may occur due to primary failure of formation of the cause of irreversible renal damage in childhood. The
ureteric bud or its inability to engage with the renal common lesions include pelviureteric junction obstrnction,
mesenchyme. The condition may occur sporadically or as vesicoureteric junction obstruction and posterior urethral
part of syndromes such as brachio-otorenal, DiGeorge, valves. Diagnosis is suspected on antenatal ultr.1sono·
Fanconi anemia, Fraser or pail-patella syndromes. Renal graphy or following presentations with dribbling of urine,
a genes is'is asymptomatic, usually detected incidentally on poor urinary stream, fever and/ or urinary tract infections.
ultrasonography. Usually, there is compensatory Chronic obstruction results in dysfunction of distal h1bules
hypertrophy of the normal kidney. A DMSA scan helps in with impaired urinary concentration and acidification,
ruling out scarring due to associated vesicoureteric reflux
or an ectopic kidney. Children with single kidney should
avoid contact sports. While affected patients are expected
to maintain glomerular function, they require annual
monitoring for hypertension and proteinuria.
Fetuses with bilateral renal agenesis or hypoplasia
rarely survive to term. Lack of fetal urine production leads
to oligohydramnios and limb anomalies. Neonates show
low set ears, flat nose, prominent epicanthic folds and
small chin (Potter fades). Pulmonary hypoplasia is the
usual cause of death.
Renal Dysplasla
Renal dysplasia implies abnormal development of re~al
parenchyma. Primitive ducts surrounded by connective
tissue, metaplastic cartilage, poorly differentiated Fig. 17.23: Multlcystlc dysplastic kidney. Multiple. thin-wall~
glomeruli and dilated tubules are present. Bilateral total and noncommunlcatlng cysts Involve the left kldneY
renal dysplasia is fatal in the neonatal period. postnatal ultrasound at one month age
Disorders of Kidney and Urinary Tract
I so1 -
leading to polyuria, polydipsia, failure to thrive, refractory are commonly associated with duplex systems, particularly
rickets and systemic acidosis. in girls. Endoscopic deroofing is the treatment of choice.
Pelviurcteric junction (PUJ) obstructio11: Stenosis of the
PUJ may be unilateral or bilateral. Obstruction is more Mlscellaneous
common in bo~s and in presence of ectopic, malrotated Re11al ectopia, renal fusion: An ectopic kidney may lie in
or horseshoe kidney. It may present as an asymptomatic the pelvis or the iliac fossa. It may be structurally normal
flank mass, or with upper abdominal pain, UTI or or hypoplastic. The patient may be asymptomatic, or have
hematuria. Ultrasonography shows a dilated renal pelvis abdominal discomfort or dysuria. A horseshoe kidney
without ureteric dilatation. Radionuclide (DTPA) renal results from fusion of identical poles of both kidneys.
sea~ shows imp~ired drainage of the affected kidney Patients with horseshoe kidney show vesicoureteric reflux
which does not improve despite administration of a in 30% cases.
diuretic. Where scintigraphy is not available, intravenous
pyelography shows renal pelvis dilatation with an abrupt Re11al duplication: A duplex (duplicated) system is a
cut-off at the PUJ. Mild cases are followed up with kidney with two pyelocalyceal systems. In patients with
ultrasound. Surgical treatment by pyeloplasty is indicated partial or incomplete duplication, either a single or bifid
if the relative function of the affected kidney is impaired. ureter is present; in those with complete duplication, two
Nephrectomy may be required for a kidney with ureters from the affected side empty separately into the
extremely poor function that does not improve despite bladder. Evaluation consists of imaging of the upper tract
temporary nephrostomy, severe hypertension or recurrent (ultrasonography, DTPA renal scan, intravenous pyelo-
urinary infections. graphy) to evaluate for obstruction and lower tract (MCU)
for vesicoureteric reflux.
Posterior uretliral valves: These are an important cause
of distal urinary tract obstruction in boys. The usual
ANTENATAL HYDRONEPHROSIS
presenting features are dribbling, abnormal urinary
stream, palpable bladder and recurrent UTI. The presence Extensive use of antenatal ultrasonography has lead to
of severe obstruction in utero may lead to renal dysplasia, increasing detection of CAKUT. On antenatal ultrasound,
with mild to moderate renal dysfunction at birth. hydronephrosis is identified in 4-5% pregnancies.
Antenatal ultrasound shows bilateral hydrouretero- However, the majority of cases of antenatal hydro-
nephrosis with or without a thick-walled bladder and nephrosis resolve without sequelae, representing transient
oligohydramnios. The diagnosis is confirmed on MCU, physiological obstruction or stasis. Patients require
which shows dilated posterior urethra and valves at its monitoring by ultrasound during the antenatal period for
junction with the anterior urethra. The bladder is enlarged progressive worsening and association with oligo-
and may show diverticuli and trabeculations; secondary hydramnios, which suggests severe lower urinary tract
vesicoureteric reflux is common. obstruction. A postnatal ultrasound is recommended
Endoscopic fulguration of the valves is performed as during the first week of life and on day 1 in severe cases.
early as possible. Alternatively, temporary urinary diver- Neonates with posterior urethral valves, solitary kidney
sion by vesicostomy or bilateral ureterostomies is or bilateral hydronephrosis and impaired renal function
necessary. Long-term follow-up is necessary since a require prompt management. Neonates showing signi-
significant proportion of patients show progressive kidney ficant unilateral or bilateral dilatation should undergo a
disease. Bladder dysfunction is common, with delayed MCU at 4-6 weeks of life to detect vesicoureteric reflux; if
continence or incontinence, poor bladder sensation and a reflux is ruled out, a diuretic renal dynamic (DTPA) scan
poorly compliant low capacity bladder. If pharmacotherapy may be required done to detect significant PUJ or VUJ
fails, patients may require clean intermittent catheterization obstruction and evaluate differential renal fm1ction. Most
~d occasionally bladder augmentation. cases with mild to moderate hydronephrosis require only
ultrasound monitoring and show spontaneous resolution
Phimosis: Up to the age of 2 years, the prepuce cannot by 2- 5 years of age. Surgery is indicated in presence of
be fully retracted because of congenital adhesions with obstructive drainage pattern associated w ith low
the glans. The diagnosis of phimosis should thus be made differential function, and/or recurrent UTI. Infants with
with caution in young children. Indications for therapy vesicoureteric reflux should receive continuous antibiotic
include recurrent balanoposthitis, forceful/ difficult prophylaxis.
urination, paraphimosis or r ecurrent urinary tract
Figure 17.24 shows a proposed algorithm for postnatal
infections.
Ureterocele: This is a congenital condition in which the
tennmal part of the ureter distends within the blad~er to
~orm a sac-like pouch. Symptoms include re.current unnary
infections, abdominal pain and urolithias1s. Ureteroceles
evaluation and .management of antenatally detected
hydronephrosis. Parents of infants with antenatal
hydronephrosis should be counseled regarding increased
risk of urinary tract infections and their prompt manage-
ment.
I
----~-·-- --
• so2 I Essential Pediatrics l
Postnatal ultrasound
Initial scan in first week; repeat at 4-6 weeks
I •
No intervention* j •
Mlcturatlng cystourethrography
Diuretic renography
Ultrasound q 3-6 months until Surgery if obstructed pattern with differential function <40%
resolution* or decline on follow-up
Monitor by ultrasound until resolution*
*Parents of infants with hydronephrosis should be counseled regarding the risk of urinary tract infections
Fig. 17 .24: Postnatal evaluation in patients with antenatal hydronephrosls. A postnatal ultrasound Is recommended at 3-7 days
except In suspected lower urinary tract obstruction. where it is done earlier. Postnatal hydronephrosis is classified using Society for
Fetal Urology (SFU) grade or renal pelvic anteroposterlor diameter (APDJ. Infants with normal findings should undergo a repeat
study at 4-6 weeks. Patients with isolated mild hydronephrosis (unilateral or bilateral) should be followed with sequential ultrasounds.
at 3 and 6 months, followed by 6-1 2 monthly until resolution; those with worsening hydronephrosis require closer evaluation.
Patients with higher grades of hydronephrosis or dilated ureter(s) are screened for underlying obstruction or vesicoureteric reflux.
Diuretic renography Is useful in detecting pelvlureteric junction or vesicoureteric junction obstruction and determining the need for
surgery.
Fig. 17 .25: Findings on ultrasonography In polycystlc kidney disease. (a) Note bulky enlarged kidney with Increased echogenlctty,
loss of cortlcomedullary differentiation and occaslonal visible cyst (arrow) In a child with autosomal recessive polycystlc kldney disease;
(b) Renal architecture Is disorganized by multiple Irregular cysts of varying sizes In autosomal dominant polycystlc kidney disease;
also note the foci of calcification
grandparents should be screened; rare cases are due to de cytosolic proteins called nephrocystins. Patients with
novo mutations. Therapy with angiotensin-converting nephronophthisis present during the first decade of life
enzyme inhibitors helps control hypertension and limits with polydipsia, polyuria or enuresis, growth retardation
hyperfiltration and proteinuria. The role of inhibitors of and renal insufficiency, acidosis and anemia. Extrarenal
the mTOR pathway (sirolimus and everolimus) and V2 features may include retinitis pigmentosa; ocular motor
receptor antagonists (tolvaptan) is being explored. apraxia, hypotonia and cerebellar or midbrain
abnormalities (Joubert syndrome); skeletal chondro-
Glomerulocystlc Kidney Disease dysplasia (Jeune syndrome); and hepatic fibrosis with
The predominant finding in glomerulocystic kidney pancreatic dysplasia.
disease (GCKD) is cysts involving glomeruli, diagnosed The diagnosis of nephronophthisis is supported by the
most definitely on renal biopsy. Ultrasonography shows ultrasound or CT finding of small kidneys with corti-
small subcortical cysts with increased kidney echogenicity comedullary cysts and poor corticomedullary differ-
and loss of cortical medullary differentiation. The entiation. Renal histology shows cysts involving the
condition may occur sporadically, with autosomal collecting ducts, tubular dilatation with atrophy and
dominant inheritance, as a part of known syndromes interstitial fibrosis. While medullary cystic kidney disease
(tuberous sclerosis, trisomy 13) or in association with other is histologically indistinguishable from nephronophthisis,
renal diseases such as dysplasia, ADPKD or ARPKD. the disease is inherited in an autosomal dominant manner,
Mutations in the hepatocyte nuclear factor ~gene lead to and presentation is delayed to adulthood.
the renal cysts and diabetes syndrome, chara~teriz~d by
GCKD, maturity onset diabetes and gemtounnary Suggested Reading
abnormalities. • Avni FE, Hall M. Renal cystic diseases in children: n~w concepts.
Pediatr Radial 2010;40:939-46
Nephronophthisis-Medullary
• Emma F, Salvia ti L. Mitochondrial cytopathie~ and the kidney.
Cystic Disease Complex Nephrol Ther. 2017;13 Suppl 1:523-528.
This group includes recessively inherited cystic disord~rs • Kwatra S, Krishnappa V, Mhanna C, ct al. Cystic diseases of
caused by mutations in genes, named NPHP 1-9, encoding childhood: A review. Urology. 2017;110:18.\-191.
I
Chapter
18
Endocrine and
Metabolic Disorders
PSN Menon • Anurag Bajpai
GENERAL PRINCIPLES
~
Endocrine glands play a crucial role in the maintenance ,,--------------------~--------------------------------,
of body physiology and homeostasis. The hypothalamic- f @ ~ @ 1
pituitary axis regulates most endocrine organs including
thyroid, adrenals and gonads, and processes like growth, !
I
I Ga J G~y I ~
~
@!J l
I
puberty, and regulation of salt and water homeostasis.
j Adenylate cyclase I :
1
m
1
hormones are slowly metabolized by the liver and excreted
Physiology
in the urine. Urinary analysis for steroid hormones thus
provides an indirect outline about their synthesis and The anterior and posterior parts of pituitary gland are
metabolism. Activation of hormones (e.g. androgen to distinct both in embryology and function. The anterior
estrogen, testosterone to dihydrotestosterone and cakidiol pituitary develops from the Rathke's pouch. Posterior
to cakitriol) is vital for the action of some hormones. pituitary originates from the infundibulum, which is a
Inactivation of hormones at the site of action prevents their downgrowth from the floor of the diencephalon. The
excess effect~ (e.g. inactivation of cortisol by ll~ principal hormones produced by the anterior pituitary are
hydroxystero1d dehydrogenase prevents its action on thyroid-stimulating hormone (TSH), adrenocorticotropic
mineralocorticoid receptor). Peripheral conversion also hormone (ACTH), follicle-stimulating hormone (FSH),
plays a_n important role in hormone function (e.g. luteinizing hormone (LH), growth hormone (GH) and
conversion of thyroxine to triiodothyronine). prolactin (PRL). These hormones regulate the actions of
target organs-adrenals by ACTH, thyroid by TSH and
Assessment of Hormone Action gonads by LH and FSH. The secretion of anterior pituitary
Endocrine assessment relies on the estimation of basal hormones is regulated by hypothalamic peptides: Growth
hormone levels (e.g. thyroid disorders), their metabolites hormone releasing hormone (GHRH), somatostatin,
(e.g. urinary metabolites in adrenal disorders), hormone dopamine, gonadotropin-releasing hormone (GnRH),
effects (e.g. U:S.ulin-like gro~th factor-1 levels in growth corticotropin-releasing hormone (CRH) and thyrotropin-
~Or_n1?ne defi~iency and urinary osmolality for diabetes
releasing hormone (TRH), and also by hormones produced
ms1p1dus), shmula~i?n tests in deficiency states (e.g. by the target glands. Posterior pituitary hormones
growth h?rmone d~fic1ency and adrenal insufficiency) and (arginine vasopressin or A VP and oxytocin) are secreted
suppression tests m excess states (e.g. growth hormone by neurons in the hypothalamic nuclei. A VP (antidiuretic
excess and Cushing syndrome). Pulsatile secretion of hormone, ADH) is the key regulator of body water and
hormones makes the assessment of many hormones by a osmolality.
single blood test arduous. Pooled samples (three blood
Growth Hormone Deficiency
samples drawn at 0, 15 and 30 minutes) are mandatory
for hormones such as gonadotropins, prolactin and Growth hormone deficiency (GHD) may be caused by
cortisol. congenital ~alformations of central nervous system
The feedback mechanism also guides the assessment (CNS), genetic defects or acquired neurological insults
of endocrine disorders. As discussed earlier, in primary (':~'able 18.1). Children with GHD have normal growth at
organ failure, pituitary hormones are elevated through birth. Growth reta~dation .becomes apparent by the age
a feedback regulation loop (e.g. thyroid-stimulating of one year. Crowding of rrudfacial structures with a round
hormone in primary hypothyroidism, luteinizing Table 18.1: Etiology of growth hormone deficiency
h~rmone and follicle-stimulating hormone with gonadal Congenital
failure and adrenocorticotropic hormone with adrenal
failure, whereas low pituitary hormone levels suggest Genetic defects
probable hypothalamic or pituitary dysfunction). The Isolated GH deficiency
feedba~k mechanism also provides the basis for dynamic Type I: Autosomal recessive
endocrme tests for diagnosis of hormone excess states Type 11: Autosomal dominant
(e.g. dexamethasone suppression test for Cushing Type 111: X-linked recessive
syndrome and glucose suppression test for growth Multiple pituitary deficiencies
hormone excess). Type I: Autosomal recessive
Type II: X-linked
Suggested Reading Idiopathic GH releasing hormone deficiency
. "":.
- 506 j Essential Pediatrics
Evaluation
History: Perinatal history, birth weight and length should
be recorded. History of birth asphyxia, breech presentation,
neonatal hypoglycemia, micropenis and prolonged
jaundice should alert the pediatrician for the possibility
of GHD. Features of chronic infections, cardiopulmonary Fig. 18.4: Achondroplasla: Note the abnormal bOdY propo
rfons
1
disorders, malabsorption and raised intracranial tension and the characteristic facies.
I so1
II
Endocrine and Metabolic Disorders
-
Tabie-18.2: Po~nters .to the etiology of shortstatu~e ·- . '1 electrolytes, liver and renal function tests and venous
Pointer Etiology - · · blood gases (renal tubular acidosis). Estimation of skeletal II
Mldline defects, Growth hormone deficiency
maturation (bone age) forms an important aspect of
mlcropenls evaluation of short stature.
Rickets Renal failure, malabsorption, renal
Step 2: The next step in evaluation involves evaluation for
tubular acidosis hypothyroidism (free T4 and TSH}, celiac disease (tissue
transglutaminase antibody) and Turner syndrome
Pallor Renal failure, malabsorption,
(karyotype in all girls).
nutritional anemia
· Malnutrition Step 3: Evaluation for GH-IGF (insulin-like growth factor)
Protein energy malnutrition,
malabsorption, celiac disease, cystic
axis is performed after common causes of growth
fibrosis retardation are excluded. This is important as systemic
illness and hypothyroidism influence the GH-IGF axis.
Obesity Hypothyroidism, Cushing syndrome,
Random or fasting blood GH level measurements do not
Prader-Willi syndrome, pseudohypo-
confirm the diagnosis of GHD, as GH hormone secretion
parathyroidism
is pulsatile. The diagnosis of GHD requires pharmacologic
Metacarpal Turner syndrome, pseudohypo- stimulation tests. GHD is suspected when the peak level
shortening parathyroidism of GH is less than 10 ng/mL following stimulation. The
Cardiac murmur Turner syndrome, congenital heart common provocative agents used are insulin, glucagon,
disease clonidine or GHRH. Levels of IGF-1 and IGF binding
. Mental retardation Hypothyroidism, Down syndrome, protein-3 (IGFBP-3) are helpful to diagnose GHD and
Turner syndrome, pseudohypo- Laron syndrome. GHD may be associated with other
parathyroidism pituitary hormone deficiencies and appropriate
investigations should be carried out to detect deficiency
of these hormones, if GHD is present. CT or MRI scans of
Corrected height SOS hypothalamic and pituitary regions are essential to rule
out developmental or acquired neurological lesions.
>-2 sos <-2 sos Management
+
No evaluation Growth velocity General measures: Management of short stature involves
correction of the underlying cause and provision of
adequate nutrition intake. Patients should be advised diet
>1 sos <-1 sos rich in protein and calorie content. They should be
Facies, body
encouraged to increase their physical activity. Iron and
Phy1lologlcal
variant proportion vitamin deficiencies should be corrected, if present. Zinc
supplementation (10 mg/ day for 3-6 months) may help in
improving growth in patients with idiopathic short stature.
Normal phenotype
•
Abnormal
Specific therapy: Initiation of specific treatment is effective
Genetic ayndrome Hemogram, LFT, RFT, bone age, chest X-ray, in restoring growth in hypothyroidism (thyroxine), celiac
Skeletal dy1plaala malabsorptlon studies, blood gas disease (gluten-free diet) and renal tubular acidosis
(bicarbonate supplements). A short course of testosterone
•
Normal
helps boys with constitutional delay of growth and
Thyroid profile, puberty. Treatment of genetic syndromes and skeletal
celiac serology, karyotype in girls dysplasias is extremely difficult. Some of them do respond
to GH therapy. Surgical techniques for bone lengthening
Normal
(e.g. Ilizarov procedure) have been used with variable
IGF-1, IGFBP-3 success in selected forms of skeletal dysplasia.
GH provocation tests Growth l1or111one: GH is highly effective patients with
GHD. GH therapy may result in increase in final height
Abnormal
•
GH deficiency
Laron syndrome
by 20-30 cm from pretreatment levels. The treatment is
given as daily night-time injections (25-50 pg/kg/ day)
till epiphyses close. GH therapy is monitored by
assessment of physical growth and bone age measurements.
Fig. 18.5: Approach to a child with short stature. GH ~ro~ Lab parameters are often not helpful to monitor GH
hormone; IGF-1 Insulin-like growth factor-1 ; IGFBP-3 IGF b1nd1ng
therapy, even though IGF-1 levels have been tried. The
Proteln-3; LFT liver function tests; RFT renal function tests:
treatment is expensive and all efforts should be made to
SDS standard deviation score
•sos I Essential Pediatrics
- - -
I
Table 18.3: Indications for growth hormone therapy Diabetes lnslpldus
Growth hormone deficiency in children and adults Polyuria (urine output >5 mL/kg/hr or 2 L/m2/day) is
Turner syndrome an important pediatric .proble~ and may be t~e only
Chronic renal insufficiency
manifestation of a senous disease such as diabetes
insipidus, diabetes mellitus, brain tumor and renal tubular
Prader-Willi syndrome
acidosis. Polyuria may result from increased solute load
Small for gestational age who fail to catch-up in growth by 2- or impaired renal concentrating capacity (Table 18.4).
3 years of age
Diabetes insipidus (DI) is an important cause of
SHOX gene mutations and Leri-Weill dyschondrosteosis polyuria. DI presents with low urine osmolality (<600
Noonan syndrome mOsm/kg) in association with high plasma osmolality
Idiopathic short stature (>300 mOsm/kg or serum sodium >146 mEq/L). DI may
be due to decreased production of vasopressin (central
ensure that treatment is given regularly for at least 2 years. DI) or its action (nephrogenic DI). Dehydration is unusual
The role of GH is expanding with increasing use in other unless there is an abnormality of thirst mechanism.
disorders with short stature such as Turner syndrome, However, infants are at a high risk of developing
chronic renal failure, small for gestational age infants who hypernatremic dehydration.
fail to catch-up, Russell-Silver syndrome, Prader-Willi Central DI: This is commonly associated with an
syndrome and idiopathic short stature (Table 18.3). intracranial pathology (Table 18.4). Craniopharyngioma
may present with DI, growth retardation and skull
Growth Hormone Excess
calcification. Germinoma located in the pituitary stalk may
Excess of GH during childhood may result in somatic be missed on routine brain scans, emphasizing the need
overgrowth or gigantism. Increased GH secretion after the to repeat neuroimaging, if no cause is found. Malforma-
fusion of skeletal epiphyses causes features of acromegaly. tions of the CNS such as septo-optic dysplasia and
Coarse features with prominent jaw, broad nose, large holoprosencephaly display central DI and deficiency of
tongue, bushy eyebrows, thick skin and dorsal kyphosis anterior pituitary hormones. Histiocytosis is the
are characteristic. Headache and visual field defects
(bitemporal hemianopia and enlargement of the blind Table 18.4: Causes of polyuria
spot) are common. Increased fluid load
Diagnosis: The diagnosis is based on clinical examination, Iatrogenic
serial photographs of the child, growth assessment and Compulsive water drinking
investigations. X-rays may show tufting of the phalanges Increased solute load
and increased heel pad thickness. MRI of brain helps to
confirm and determine the extent of the tumor. IGF-1 is Osmotic diuresis: Diabetes mellitus, mannitol treatment
the best screening test for GH excess. Non-suppressible Salt loss: Adrenal insufficiency, diuretics, cerebral salt wasting,
aldosterone resistance
GH levels confirm the diagnosis after a glucose challenge.
Pituitary gigantism is rare in children. It may be the Impaired urinary concentration
only clue to an underlying pituitary adenoma, which may Inefficient ADH action (diabetes insipidus, DI)
be associated with isolated or multiple endocrine Central DI (neurogenic DI)
abnormalities in the setting of multiple endocrine Genetic defects
neoplasia or McCune-Albright syndrome. Malformations: Septo-optic dysplasia, holoprosencephaly,
Differential diagnosis: GH excess differs from Sotos anencephaly
syndrome (cerebral gigantism), which is characterized by CNS insults: Head trauma, neurosurgery, infection, brain
large size at birth, excessive growth in early childhood, death
and advanced height, weight and bone ages. The skull is Infiltrative disorders: Sarcoidosis, histiocytosis
large with prominent forehead and jaw, high-arched Space occupying lesions: Craniopharyngioma, gerrninorna
palate, hypertelorism and antimongoloid slant of the Nephrogenic DI
palpebral fissure. Tall stature due to hereditary tall stature, Genetic: X-linked N2 receptor), AR and AD (aquaporin defect)
obesity, precocious puberty, Marfan syndrome and Acquired: Hypokalemia, hypercalcemia, obstructive
uropathy, nephrocalcinosis
homocystinuria should be ruled out by appropriate tests.
Tubulopathy
Management: Medical management involves the use of long- Renal tubular acidosis
acting somatostatin analogs such as octreotide. The GH Bartter syndrome
receptor antagonist, pegvisomant is also useful in treatment. Gitelman syndrome
Partial or complete resection of pituitary adenoma is AD: Autosomal dominant; ADH: Antidiuretic hormone; AR: Autosornal
indicated, if there is evidence of raised intracranial tension. recessive
Endocrine and Metabolic Disorders I sog •
comJI\onest infiltrative disorder associated with central Confirm polyurla 2
Urine output <2 lJm /day
DI. Neurological infections including tuberculosis may Document urine output No further evaluation
manifest with central DI later.
2
Urine output >2 Um /day
Nepltrogenic DI: This results from inherited or acquired Urine osmolality
resistanc~ to ~asopressin. Congenital nephrogenic DI due
to mutaho~ m ~asopressin receptor (V2) presents in
infancy with failure to thrive, recurrent fever and <300 mOsm/kg >300 mOsm/kg
Inefficient aldosterone action: These include adrenal Investigations: Initial investigations should include
insufficiency, isolated aldosterone deficiency or testing for ~uine sugar and early morning specific gravity
aldosterone resistance. They present with hyponatremia, or os~~lahty. Blood gases, urea, electrolytes, calcium and
hyperkalemia and dehydration. The condition may be creatinine should be estimated. High plasma osrnolality
lethal. Failure to thrive is common. Pigmentation is (>300 mOsm/kg or sodium >146 mEq/L) with low urine
characteristic of adrenal insufficiency. Polyuria and salt osmolality .(<300 m~sm/k~ and urine specific gravity
wasting in the neonatal period should prompt evaluation <l.005) suggest the diagnosis of DI, which needs further
for congenital adrenal hyperplasia (CAH). Genital classification on the basis of response to AVP. Patients
ambiguity in girls is a clue to the diagnosis of CAH. with normal plasma osmolality and low urine osmolality
I
Hypothalamus Table 18.6: Etiology of hypothyroidism
TRH Primary (thyroid, >95%)
Autoimmune thyroidit/s
Enzyme defects: Trapping, organification, thyroglobu lin
synthesis, deiodination
Iodine deficiency: Endemic goiter
Dysgenesls: Aplasia, dysplasia, ectopia
TBG Thyroid Injury: Surgery, radiation, infection
Goitrogens: Thiocyanates, thionamides, lithium, amiodarone
Transient causes: Maternal TSH receptor blocking antibody,
iodine excess, maternal antithyroid drug
End organ
Secondary or tertiary (hypothalamus or pituitary, <5%)
fig. 18. 7: Regulation of hypothalamic-pituitary-thyroid axis. FT3
Malformations: Septo-optic dysplasia, holoprosencephaly
free trllodothyronlne; FT4 free thyroxine; T3 trliodothyronine; T4
thyroxine; TBG thyroxine binding globulin; TRH thyrotropln- Genetic defects
releaslng hormone; TSH thyroid-stimulating hormone CNS insults: Trauma, surgery, radiation, infection
CNS tumors: Craniopharyngioma, germinoma
thus be estimated after 48 hours after birth as a part of
Peripheral (extremely rare)
neonatal screening for congenital hypothyroidism.
Resistance to thyroxine
Assessment of Thyroid Function CNS: Central nervous system; TSH: Thyroid-stimulating hormone
Thyroid function is assessed by serum TSH and free and/ complete agenesis, partial agenesis to ectopic thyroid.
or total T4 and T3 . TSH is the most sensitive indicator of Increased incidence of thyroid dysgenesis is noted in
primary (thyroidal) hypothyroidism, but is not as helpful Down syndrome. Biosynthetic d efects include disorders
in the diagnosis of central (pituitary or hypothalamic) affecting iodine transport, peroxidation, thyroglobulin
hypothyroidism. Serum T4 level is a better indicator of synthesis and deiodination. Pendred syndrome, a disorder
thyroid status than serum T3 due to increased conversion of the pendrin gene, is associated with d ecreased
of T4 to T3 during thyroid-depleted states. Considering intracellular transport of iodine and deafness. Nongoitrous
the variability in the levels of circulating thyroxine-binding congenital hypothyroidism is known to be associated with
globulin (TBG), estimation of free thyroid hormones is genes TSHR, PAXB and TSHB . Transient congenital
superior to total hormone levels in the diagnosis of h ypothyroidism may occur following transplacental
hypothyroidism. Low free T4 (Ff4 ) and low TSH levels passage of TSH receptor blocking antibodies, iodine
suggest central hypothyroidism, while low FT4 levels with exposure and treatment with antithyroid drugs (e.g.
high TSH levels indicate primary hypothyroidism. amiodarone).
Persistent elevation of TSH in the presence of normal FT4
suggests subclinical hypothyroidism. Elevated FT4 and Clinical features: Features of congenital hypothyroidism
undetectable TSH levels imply a hyperthyroid state. are nonspecific and often difficult to identify in the
neonatal period. They become prominent with increasing
Hypothyroidism age. However, the window period for neurological
Hypothyroidism is caused by defects in the hypothalarnic- intervention would have elapsed in most children bv that
pituitary axis (central hypothyroidism), thyroid gland time. This underscores the need for neonatal scre~ning
(primary hypothyroidism) or the peripheral sensitivity to for congenital hypothyroidism. Clinical manifestations
thyroxine {Table 18.6). include hoarse cry, facial puffiness, umbilical hernia,
hypotonia, mottling of skin and leth argy (Fig. 18.8).
Congenital Hypothyroidism Prolonged jaundice, constipation and unexplained
Congenital hypothyroidism is the most common hypothermia may also indicate hypothyroidism. Open
preventable cause of mental retardation. Congenital posterior fontanel is an important indicator of congenital
hYPothyroidism is more commonly reported in India (1 hypothyroidism (Table 18.7).
in 1000 newborns) compared to western countries (1 in
Eval1111tio11: History of maternal thyroid disease or
4000).
ingestion of antithyroid medications should be probed.
Etiology: With wider coverage of iodine supplementation Family history of hypothyroidism suggests dyshormono-
program, the incidence of iodine deficiency has declined genesis, while recurrent transient hypothyroidism
and thyroid dysgenesis has emerged as the most common indicates a disease related to maternal TSH receptor
cause of congenital hypothyroidism in India (7~% of all antibody. Residence in iodine deficient area may suggest
cases). The disorder encompasses a spectrum rangmg from the diagnosis of iodine deficiency. Presence of goiter
-512 I ~~----~~~~~~----~=E=ss~e~n~t~ia~l~P~e~d~la~tr~lc~s=-------~~--~~~~~~~-~
IThyroid scan I
+ I +
No uptake Ectopic uptake Increased uptake
i i
~cthyrold I Dyshormonogenesis
Iodine deficiency
Negative Positive
011tco111e: Early diagnosis and treatment following Evaluntion: Severe short stature and intellectual disability
neonatal screening has resulted in normal intellectual suggest missed congenital hypothyroidism. A firm and 1
outcomes. Outcome is, however, poor in children with
congenital hypothyroidism who have been diagnosed
non-nodular goiter implies iodine deficiency or disorder 1
of thyroid hormone synthesis; firm nodular goiter
beyond the neonatal period. Mental retardation and short indicates autoimmune thyroiditis. Family history of
stature are common sequels. acquired hypothyroidism suggests autoimmune
thyroiditis. Children with central hypothyroidism should
Screening: Difficulty in early identification of congenital
be evaluated for other pituitary hormone deficiencies
hypothyroidism and the disastrous consequences of
including MRI of the hypothalamic-pituitary region.
delayed diagnosis have led to neonatal screening for
Antibodies to thyroid peroxidase enzyme (anti-TPO)
hypothyroidism. Screening programs use dried blood
should be estimated in acquired primary hypothyroidism.
sample collected at postnatal age of 2 to 4 days. The most
commonly used strategy screens first for TSH. Care should Managemc11t: Treatment of acquired hypothyroidism
be taken to use appropriate cutoff for TSH levels as per should be gradual. A dose of 100 µg/m 2 /day is
age. Higher levels of TSH are used initially as cutoff for recommended (Table 18.9). In long-standing cases, initial
treatment (more than 40 mU /L). TSH-based screening has treatment should be started at 25-50% of these doses with
higher sensitivity compared to T4 -based approach. gradual build up every 3-4 weeks. Thyroxine should be
However, TSH-based approach does not identify central given in empty stomach in the morning. Follow-up should
hypothyroidism. T4 first approach can identify these be done every three months during the first two years of
children, but has the disadvantage of missing cases with therapy and six monthly thereafter. The doses should be
compensated hypothyroidism. modified to maintain TSH levels in the normal range. Most
children require lifelong therapy.
Acquired Hypothyroidism
Etiology: Autoimmune thyroiditis is the most common Subclin/cal Hypothyroidism
cause of acquired hypothyroidism. This is more common Mild elevations of TSH (below 10 mU / L) with normal Ff4
in girls. Goiter is often nodular and firm unlike the soft levels are frequently observed in children especially with
and uniform goiter seen in dyshormonogenesis. Anti- obesity. The clinical relevance of subclinical h ypo-
thyroid peroxidase (anti-TPO) antibodies are usually thyroidism is unclear. In most cases, these findings reverse
present. Autoimmune thyroiditis may be associated with over a period of three to six months and do not require
other autoimmune endocrinopathies such as adrenal treatment. Treatment should be considered in children
insufficiency, type 1 diabetes mellitus and hypopara- with thyromegaly, presence of anti-TPO antibodies, or
thyroidism. Rarely, congenital abnormalities, e.g. thyroid family history of hypothyroidism.
dysgenesis or an inborn error of thyroid hormone
synthesis may become evident in older children and Goiter
adolescents. Iodine deficiency and goitrogens are other Goiter refers to the enlargement of the thyroid gland. From
causes of primary hypothyroidism in older children. a clinical standpoint, thyromegaly is diagnosed \Vhen the
Secondary hypothyroidism due to combined hypothalamic- lateral lobe of the thyroid is larger than the terminal
pituitary defects could be a manifestation of neurological phalanx of the thumb of the child (Fig. 18.10).
insults or tumors.
Etiology Goiter may be associated with diminished,
Clinical features: Features of acquired hyp?t~yroidism normal or increased thyroid function (Table 18.10).
are subtle compared to congenital hypothyroidism. Often Thyroid enlargement may represent increase in size in
short stature may be the only manifestation. Cold response to compensatoryTSH secretion (hypothyroidism),
intolerance lethargy, constipation, delay in dentition and infiltration (autoimmune thyroiditis, neop lasm s
poor school performance may suggest hypothyroidism. or hemochromatosis), or presence of TSH receptor
All children with unexplained developmental delay, stimulating antibodies (Graves disease). Important causes
mental subnormality and short stature should be
evaluated for hypothyroidism. Most patients with Table 18.9: Recommended dose schedule of thyroxine
hypothyroidism have delayed pu?~rty; how~ver, Age Thyroxine dose, µglkg/day
uncontrolled long-standing hypothyro1d1sm m~y t_ng~er Neonatal period 10-15
precocious puberty in girls. Goiter is commo.n ~iodine
1-6 months 6-10
deficiency, chronic lymphocytic thyroi~ihs a~d
dyshormonogenesis. Hypothyroidism is associated with 1-5 years 4-6
Down syndrome, Turner syndrome, ~eliac disease and 5-12 years 3-5
type 1 diabetes. Children with these disorders sho~ld be 12-18 years 2-3
periodically screened for hypothyroidism even m the >18 years 1-2
absence of symptoms.
11 s14 Essential Pediatrics
~
functions are normal. Ultrasound and fine needt
aspiration should be performed, if no clue to etiology~
identified.
Mauagemeut: Treatment should be directed to the caUSe
(antithyroid medications in Graves disease; thyroxine in
hypothyroidism). Children with autoimmune thyroiditis
should be followed with annual thyroid function tests.
Suppressive thyroxine therapy for euthyroid goiter is of
limited benefit and is best avoided. Surgery is indicated,
only if goiter is large enough to cause respiratory
embarrassment.
. -
I .
'Iodine deficiency
Median urine iodine, µg/L
Goiter prevalence
Neonatal thyroid stimulating hormone, >5 mU/L whole blood
N~ne
>100
<5%
<3%
Mild
50-99
5-20%
3-20%
Moderate
20-49
20--30%
20-40%
Severe
<20
>30%
>40%
II
cretinism None None Present Present
Assessment of iodine deficiency disorders and monitoring their elimination: A guide for programme managers. 3rd ed. 2007, WHO
Endemic cretinism: This is a disorder associated with Table 18.13: Etiology of hyperthyroidism_
endemic goiter and severe iodine deficiency with
Infancy
characteristic clinical features, which include deaf-mutism,
squint, mental retardation and characteristic spastic or Transplacental passage of thyroid antibodies
rigid neuromotor disorder. Two types of endemic TSH receptor activating mutation
cretinism are described . Neurological cretinism is After Infancy
characterized by deaf-mutism, squint, proximal spasticity Graves disease (TSH receptor stimulating antibody)
and rigidity (more in the lower extremities), disorders of Release of preformed thyroid hormone: Subacute thyroiditis
stance and gait with preservation of vegetative functions, Toxic thyroid nodule, toxic multinodular goiter
occasional signs of cerebellar or oculomotor disturbance Iatrogenic
and severe mental deficiency. Retarded psychomotor Pituitary resistance to T3
development, severe short stature, coarse facial features
and myxedema without deaf-mutism characterize common. Examination reveals firm homogeneous goiter.
myxedematous cretinism. Iodine deficiency is also Eye signs are relatively uncommon compared to adults
associated with poor school performance in children and and are related to sympathetic over-activity (lid lag,
recurrent pregnancy loss in women. ophthalmoplegia, absence of wrinkling) or autoimmune
infiltration (chemosis, proptosis). Tachycardia, cardiac
Prevention a11d control: Iodine deficiency disorders are
arrhythmia and high output cardiac failure may occur.
best prevented as treatment is usually ineffective.
Iodinated salt or iodized oil are highly efficacious in Diagnosis: The diagnosis is confirmed by the demonstra-
preventing iodine deficiency. Treatment of endemic tion of elevated serum free T4 and T3 levels. The presence
cretinism may eliminate signs of hypothyroidism but of goiter, infiltrative eye signs and hyperthyroidism are
neuromotor and intellectual deficiency are irreversible. suggestive of Graves disease. Absence of goiter should
Surgical removal of large goiters is indicated only to raise the possibility of transient hyperthyroidism as part
relieve airway obstruction or for cosmetic reasons. of autoimmune thyroiditis. Differentiating thyrotoxicosis
The National Goiter Control Program.me of the Ministry from thyroiditis is important, as antithyroid drugs are not
of Health and Family Welfare in India began in 1962 with required in children with thyroiditis who may progress
establishment of salt iodination plants. The program is to hypothyroidism. Diffusely increased radiotracer uptake
directed towards control of iodine deficiency disorders is suggestive of Graves disease while reduced uptake is
and ensuring that only iodized salt is used in India. The characteristic of thyroiditis.
recommended daily intake of iodine is 40-120 µg for
children up to the age of 10, 150 µg for older children and Management: Antithyroid drugs are ineffective in the
adults and an additional 25 µg and 50 µg during acute phase due to lag period in their onset of action.
pregnancy and lactation, respectively. Based on an Propylthiouracil is contraindicated in children due to
hepatotoxicity. Treatment should be started with
assumption of a mean intake of salt of 5 g/day, the
methimazole (0.5-1.0 mg/kg/day) in 3-4 divided doses.
recommended level of iodination is one part of iodine in
Beta-blockers (propranolol 2 mg/kg/ day in two divided
25,000 to 50,000 parts of salt.
doses) are effective in ameliorating of sympathetic
HYPerthyroldlsm symptoms. Iodinated contrast (idopate 0.001 µg/kg/ day)
and Lugol iodine (5% iodine and 10% potassium iodide;
HyPerthyroidism is relatively uncommon in children. It
126 mg/mL iodine, 1 drop 8 hourly) are effective in
is most commonly seen in young girls, caused by Graves
reversing of features of hyperthyroidism. Prednisolone (1-
disease (Table 18.13).
2 mg/kg/day) inhibits peripheral conversion of T~ to T3
Clinical features: The condition should be suspected in and is useful in treatment of hyperthyroid storm. Cardiac
children with weight loss with increased appetite, tremors, failure refractory to these measures requires treatment
diarrhea, warm extremities, increased sweating and with digitalis.
anxiety. Inability to concentrate, personality changes, Surgery and radioiodine ab la tion should be considered
lllood instability and poor school performance are in patients with failure of medical management. Patients
- 516 I E11ont101 Podlntrlc•
with large or toxic nodular goiter require ptll'tltll u1· lulnl PTH 1t1c1'1JntH.J£1 no rum colclum hy Hti mulaUn~ bone
thyroidectomy. Radioiodine (1311) is now increm;lngly llst•d rc1Jorptfon (oah!obhrnt), cr1lcltrl11I proJui::tlon (proximal
in the management of childhood Grnves dlscttsc. t11bu lo) nnd ru11n I cll lclt1 m rNiorpt ion ( d 1,,tal tubule).
Cn lcllrlol lH tile only 110rmonc tlrnl rc~ulawi; in!J:1:lin-'ll
Neonatal Hyperthyrofdism cnlclum 11bf1orptlo11. Cnlcltrlol 111 formed by ar:tivation of
One percent of babies bom to mo Uters with Grnws dlscm~u vHnmln IJ In tho llvtr (2'.l-hydr11xylatlon) ilnd kidney (1tt,..
show fetal thyrotoxicosis and cardinc foil me. Mnnngcmcnt hydruxylHllon). Sunllg lil h1 the major r:<mrcc of vltaminO
includes maternal antithyroid drngs nnd digitnllznllun . with minor co11lrlb11llon from dlc:ta ry liOlH C<:b. t",..
This usually occurs within the first week of life but nrny hydroxylm1e enzyme In the klc.lnc:y~ iH the ratc·limiling lllf.-p
be delayed, if mother is on antithyroid medictttions or hm1 of cnlcltrlol l'.lyntheHIH. C11 lcllonin, rwcn:ted by the
concomitant TSH receptor blocking antibody. Treatment pnl'l\fullkulnr cclll'.I of thyroid in re11p<inflc lo elevated
should include antithyroid drugs, proprnnolol and en lei um lcvcll'.I, lowcrn ~cr11m c1:1lcl um levels by dccrcai;ing
corticosteroids. The condition is self-limiting and resolves bone resorption llnd lncrca1:1 ing urinary cillciurn excn:tion.
over 3-6 months. lt hns n minor role on calcium hom<:osta.,is.
Evaluation
action of PTH characterize these disorders. Hypopara-
thyroidism may occur as part of congenital maliormation Evaluation is directed towards identification of etiology
or acquired destruction of the parathyroid glands. and assessment of the severity of illness.
Autoimmune hypoparathyroidism is the most common Clinical: Detailed history of the age of onset, presenting
form in older children and frequently associated with features, frequency of episodes of hypocalcemia and
autoimmune polyendocrinopathy type 1. family history should be obtained. Neonates should be
DiGeorge syndrome characterized by abnormal screened for prematurity, birth asphyxia, maternal
development of third and fourth pharyngeal pouches is hyperparathyroidis m and initiation of top feeds .
caused by deletion of part of chromosome 22q. lbis results Congestive cardiac failure, recurrent infections and
in maldevelopment of thymus (resulting in T cell abnormal fades are suggestive of DiGeorge syndrome.
immunodeficiency), parathyroid glands (resulting in
hypoparathyroidism), heart (resulting in conotruncal Investigations: Initial evaluation should include serum
defects) and face (abnormal fades). Activating mutation phosphate levels, renal and liver function tests and serum
of calcium-sensing receptor is associated with low PTH alkaline phosphatase (Table 18.15 and Fig. 18.11).
and calcium levels with paradoxically increased urinary Phosphate regulation is dependent on PTH and inefficient
calcium excretion (familial hypercalciuric hypocalcemia). PTH action results in hyperphosphatemia. Hypocakemia
due to decreased vitamin D action is associated with
Hypomagnesemia is an important cause of transient secondary hyperparathyroidism and low phosphate
hypoparathyroidism and should be excluded in children levels. Thus hypocalcemia with hyperphosphatemia in the
with refractory hypocakemia. absence of phosphate load (exogenous or tissue lysis) and
normal renal function suggests parathyroid insufficiency.
P7H resistance (pseudoliypoparatlryroidism, PHP): lbis Hypomagnesemia should be considered in patients with
is caused by an inactivating mutation in the gene encoding refractory hypocalcemia and normal or low phosphate
for stimulatory subunit of G protein (Gsa). lbis presents levels. 25-hydroxyvitamin D levels should be measured
with clinical features of hypoparathyroidism in the wake in children with rickets to identify vitamin D deficiency.
of elevated PTH levels. PHP may be associated with the
phenotype of Albright hereditary osteodystrophy such as Management
round facies, brachydactyly, short stature, obesity, short
fourth and fifth metacarpals (brachymetacarpia), In children with severe hypocalcemia (ionic calcium
osteodystrophy and heterotopic ossification. <0.8 mmol/L), parenteral calcium should be administered
(2 mL/kg intravenously over 5-10 min) after obtaining
Vitamin D related: Vitamin D deficiency (nutritional, blood sample for calcium. Cakium gluconate (10%, 9 mg
rn~Iabsorption), decreased la-hydroxylase ac~on (renal calcium per mL) is the preparation of choice. Care should
failure, vitamin D-dependent rickets type I), mcreased be taken to administer the drug slowly (to avoid cardiac
inactivation of vitamin D (antiepileptic drugs) and effects) and avoid extravasation (to prevent skin necrosis).
- 518 j -~----~~~~~~------~E~s~s=e~n~tl~al~P~e~d~la~t~rl~c!s------~------~~~~~~----
~
- Table1e.i5: Laboratory features- of common causes of hypocalcemia -,
Phosphate 2s-hydroxyvitamin D Parathyroid hormone (PTH)
Disorder
High
Vitamin D deficiency Low, normal Low
Normal High
Renal failure High
Normal Low
Hypoparathyroidism High
Normal High
Pseudohypoparathyroidism High
Normal Low
Hypomagnesemia Low, normal
Cholesterol
SIAR
Mitochondrial transport
OHEAS
I
CYP11A1
POR POR
Androstenediol
Pregnenolone 1 - - - -- i 17-0H pregnenolone DHEA HS017
L - -- - - r -- - - - ' CYP17A1 , CYP17A1, L...----~----
HS03B2
HSD3B2 17a-Hydroxylase HSD382 17, 20-lyase HSD382
Corticosterone CORTISOL
CYP11B2
18-Hydroxylase
18-0H-Cortlcosterone
CYP11B2
18-oxidase
ALDOSTERONE
Ag. 18.12: Pathways of steroid blosynthesls. The key enzymes mediating synthesis of principal steroids are named according to
their site of action and the nomenclature of cytochrome P450 enzymes. StAR steroldogenlc acute regulatory protein;
DOC deoxycortlcosterone; DHEA dehydroeplandrosterone; DHEAS DHEA sulfate; DHT dlhydrotestosterone. The enzyme nomenclature: CYPl lAl :
P450 side chain cleavage enzyme, P450scc or 20.22-desmolase; HSD3B2: 3p-hydroxysterold dehydrogenase type 2; CYPl 7A1: 17a-hydroxylcse
orl 7,20 lyase; CYP2 l A2: 21-hydroxylase; CYPl l B1: 11 P-hydroxylase; CYP 11 B2: This has 3 actlons-11 P-hydroxylase, 18-hydroxylase and 18-oxldcse;
POR: P450 oxldoreductase, CYPl 9A l: Aromatase, HSDl 78: 17P·hydroxysterold dehydrogenase, SRDSA2: Scx·reductase type 2
Aldosterone acts on distal renal tubules and collecting hypercortisolism caused by an ACTH-producing pituitary
ducts of kidneys to promote sodium and fluid tumor. Classic features of Cushing syndrome such as
reabsorption. Aldosterone deficiency causes urinary salt- central obesity, striae, moon fades and buffalo hump are
wasting resulting in salt-wasting crisis (hyponatremia, rare in children (Fig. 18.13). Growth failure and obesity
hyperkalemia and metabolic acidosis). are common; other features include hypertension,
hirsutism, delayed puberty, behavioral problems, bone
Adrenal androgens are necessary for the development of
pain and muscle weakness.
pubic and axillary hair in girls.
Adrenocorticotropic 'llormone (AClli), a polypeptide Etiology: Cushing syndrome may be caused by increased
secreted by the anterior pituitary, is the major regulator endogenous production or exogenous administration
of glucocorticoid and androgen synthesis. Intravascular (Table 18.16). Prolonged steroid treatment is the
volume, serum potassium levels and renin-angiotensin commonest cause of childhood Cushing syndrome.
system are the chief regulators of aldosterone synthesis. Increased adrenal glucocorticoid production may be
ACTH has only a minor role in aldosteron~ reg~l~tion. related to increased ACTH levels or represent autonomous
~CTH deficiency as in secondary adrenal 11~suffic1ency adrenal hyperfunction. Adrenal pathology is more likely
is, therefore, not associated with salt-wasting. ACTH in young children, while pituitary causes are common
secretion is stimulated by hypothalamic corticotropin- after puberty. Ectopic ACTH production is rare in
releasing hormone (CRH) and suppressed by cortisol as chlldren.
part of a feedback loop.
Evaluation: Investigations are directed towards
Adrenocortical Hyperfunctlon-Cushing Syndrome confirming the diagnosis of Cu shing syndrome and
The most common disorder of adrenocortical hyperfunction finding the etiology. Commonly used screening tests
is Cushing syndrome. The term Cushing disease refers to include assessment of diurnal cortisol rhythm, overnight
- s20 1 Essential Pediatrics
~
dexamethasonc suppression test (cortisol ll•vl'ls •lhi•r
single midnight dose of dex111Y1c th nsono O,'.\ "'~/ n ~'.
maximum dose 1 t~'g) nn~ ~.:\-hm~r urinu frl' t1 cnrtlii~l
(Table 18.17). The drngnns~s 1s conhrnwd with lnw c\C\sl'
dexamethasone suppression tes . cortls11l ,,h q,
. lt (sc rum
dexamethasone 5 pg/kg every 6 '\llll'S lor two dily~).
The most important pnrt of cvnhmtinn of'' l'hlhl Will
Cushing syndrome is to differentiate ACTH·dl'pt•ndt•n~
causes from autonomous 11drcnnl steroid prnthwtlon
(Table 18.18) . ACTH levels difforcnti111\• ACTH.
independent (ACTH levels <5 pg/mL) from /\CTI\.
dependent conditions (ACTH levels >l5 p~/ ml.). l'.clnpk
ACTH production should be suspected in chlldrt' n w\\h
extremely high ACTH levels (>100 pg/mL). 1ll~h dost.'
dexamethasone suppression test is based on the prlnclplt•
~-.L~UUIU .• I that high doses of this agent suppress ACTH production
Fig. 18.13: Cushing disease secondary to pituitary adenoma. in individuals with pituitary lesions but not in thost~ with
Note the moon face and hypertrichosis over forehead and ectopic ACTH production (Fig. 18.14).
upper lip Adrenal tumors in children are usunlly lm·gc l\llll
identifiable on ultrasound. Magne tic reson11ncc iml\~in~
Table 18.16: Etiology of Cushing syndrome of the hypothalamic-pituitnry region should b0 1wrinrm(\I
ACTH-dependent causes in children with ACTH-dependent Cushin~ sy ndroml'.
Hypothalamic lesions: Increased corticotropin production Inferior petrosal sinus sampling is the tes t for identifying
Pituitary lesions: Microadenoma, macroadenoma the source of ACTH production and should be pl'rfornwd
Ectopic lesions: Neuroblastoma, carcinoid tumor, Wilms tumor in children with ACTH-dependent Cushing symlrnnw
with normal neuroimaging.
ACTH Independent causes
M1m 11gc111r11 t : Resection of adrenal lesion is rccomnwmkd
Ad~enalcarcinoma, adenoma
for adrenal adenoma and carcinoma. Prolongl'd cortisol
Pigmented nodular hyperplasia
excess causes suppression of the norm11l contr.1blernl
McCune-Albright syndrome
adrenal gland. This mandates close monitoring for t1d ren,1l
Exogenous administration insu.fficien~y i.n the perioperative p e riod . Adrenal
Glucocorticoids carcinoma is lughly malignant and has a high rntc of
ACTH recurrence. Pigmented nodular hyperplasia should be
ACTH adrenocorticotropic hormone
+:
Negative
[ Urine free cortisol, ONDST
I
j
+
Positive
Tabi8 ie°!19: Etiology of hyperaidosteronism
Primary hyperaldosteronlsm
Adenoma, hyperplasia .
Glucocorticoid remediable hyperaldosteronism
I
Cushing syndrome unlikely Secondary hyperaldosteronlsm
Renal artery stenosis, renin-secreting tumor
Cardiac failure, nephrotic syndrome, liver disease
< 5 pmol/L ~10 pmol/L > 10 pmol/L Other causes of excessive mineralocortlcold action
\ CR1test I Apparent mineralocorticoid excess (deficiency of 11 P-
hydroxysteroid dehydrogenase)
+:
Negative
+
Positive-. MRI head
Liddle syndrome . .
Congenital adrenal hyperplasia due to def1c1ency of 17a.-
hydroxylase or 11 p-hydroxylase
1-- - Positive
Adrenal lesion Evaluation: Hypokalemic alkalosis in a c~ld with low
HRCT adrenal Negative renin hypertension should prompt evaluation for t:ue ~r
+
Ectopic ACTH Pituitary lesion
apparent aldosterone excess. High aldosterone level.in this
setting is suggestive of primary hyperaldosteroru~m or
GRA. Decrease in aldosterone levels and resolut10n of
fig. 18.14: Approach to Cushing syndrome in children. ACTH clinical and laboratory features after dexamethasone
adrenocortlcotropic hormone; CRH corticotropln-releaslng
hormone; HRCT high resolution computed tomography scan; suppression suggests GRA; no effect is s~en in primary
IPSS inferior petrosal sinus sampling; LDDST low dose hyperaldosteronism. Diagnosis of pnmar~ hyi:>er-
dexamethasone stimulation test; ONDST overnight dexa- aldosteronism should be confirmed by adrenal rmagmg.
methasone stimulation test
Management: Hyperaldosteronism should be manag~d
with salt restriction and aldosterone antagonist
treated with bilateral adrenalectomy. Trans-sphenoidal (spironolactone, eplerenone). Physiological hydrocortisone
resection of. pituitary adenoma is recommended for replacement suppresses ACTH secretion in glucocorticoid
Cushing disease. remediable aldosteronism resulting in resolution of
Medical management of Cushing syndrome with hyperaldosteronism and hypertension. Surgery is the
inhibitors of steroidogenesis (ketoconazole, aminoglute- treatment of choice for adrenal adenoma.
thimide, cyproheptadine, metyrapone and mitotane) has
been tried with variable results. Pheochromocytoma
Pheochromocytoma is a catecholamine-secreting tumor,
Aldosterone Excess arising from chromaffin cells of adrenal medulla. It can
Hyperaldosteronism is associated with fluid and so~ium also arise from the abdominal sympathetic chain, peri-
retention along with increased urinary loss of potass1':1m. adrenal area, or in the thoracic cavity. The condition is
The chief clinical features of primary hyperaldosterorusm rare in children and coexists with other syndromes such
are hypertension and hypokalemic alkalosis. Primary as neurofibromatosis, von Hippel-Lindau disease and
hyperaldosteronism due to increased adrenal aldosterone multiple endocrine neoplasia type II. Compared to adults,
production is extremely rare. Secondary h yperaldo- pheochromocytoma is more likely to be bilateral and
steronism results from factors that activate the renin- associated with underlying genetic anomaly in children.
angiotensin system.
Clinical features: Excessive secretion of catecholamines
Etiologtj: Primary hyperaldosteronism may be cau~ed.by results in hypertension, which is u sually sus tained and
diffuse hyperplasia or adenoma. Gluc~cor~1co1d often paroxysmal. The clinical symptoms include
remediable aldosteronism (GRA), a genetic disorder headache, palpitation, pallor, sweating, nausea, vomiting,
involving chimeric fusion of CYPllBl ~romoter ~d the visual disturbances and occasionally convulsions.
coding region of CYP11B2, results m regula tion of
aldosterone secretion by ACTH and ther~by, hyperaldo- Evaluation: The diagnosis should be considered only after
steronism. Primary hyperaldos teronism s~1ould be other common causes of childhood hypertension such as
differentiated from secondary hyperaldostero~sm (renal renal parenchymal disorders, renal artery stenosis and
failure, congestive ca rdiac failure, liver d1se~se and coarctation of aorta have been excluded. Diagnosis is
nephrotic syndrome, and apparent and real mmeralo- established by demonstration of increased urinary
corticoid excess (Table 18.19). excretion of catecholamines a nd their d e rivatives.
Essential Pediatrics
- s22 1
Ultrasound, CT scan, MRI scan and 1231 metaiodo- hyperpigmented such as areola and genitalia. Pigm~
I benzylguanidine (MIBG) scintigrap.hy are used for
localization. Often the tumors are multiple.
Management: Surgery is the treatment of choice.
Transabdominal exploration of all the sites with removal
tion is absent in children with secondary adrenal
insufficiency.
Evaluation: All patients suspected to have adrenal
insufficiency should undergo urgent testing for serum
of tumors is advocated. Preoperative alpha blockade is electrolytes and blood sugar. Basal levels of cortisol are
needed using phenoxybenzamine and prazosin. Recently, low but can be in the normal range. Elevated plasma renin
calcium channel blocking agents have been used activity indicates mineralocorticoid deficiency. ACTH
successfully. stimulation test (cortisol estimation 60 minutes after
0.25 mg of intramuscular or intravenous ACTH injection)
Adrenal Insufficiency is the best test for adrenocortical reserve. Serum cortisol
Adrenal insufficiency may be related to adrenal defects levels lower than 18 µg/ dL are suggestive of adrenal
(primary adrenal insufficiency; autoimmune destruction, insufficiency.
infection, steroidogenic defect, hemorrhage), decreased The next step in evaluation of adrenal insufficiency is
ACTH production (secondary adrenal insufficiency) or estimation of ACTH levels. Elevated ACTH levels suggest
ACTH resistance. primary adrenal pathology while low levels points
towards pituitary defect. Further evaluation of primary
Etiology: Autoimmune adrenal dysfunction is the adrenal insufficiency includes abdominal CT scan and
commonest cause of primary adrenal failure (Addison
workup for tuberculosis.
disease) beyond infancy. Autoimmune adrenal failure is
often associated with autoimmune polyendocrinopathy Ma11ageme11t·: The initial management of salt-wasting
type 1 and 2. Infections due to tuberculosis and human crisis includes correction of shock by fluid boluses. Hydro-
immunodeficiency virus (HIV) are known to result in cortisone is given immediately at a dose of 50 mg/m2,
primary adrenal failure. Adrenal hemorrhage in the followed by 100 mg/ m 2 I day in four divid ed doses.
setting of meningococcal and other bacterial infections Frequent monitoring of hemodynamic parameters, urine
(Waterhouse-Friderichsen syndrome) is an important output and serum electrolytes are required. Once the child
cause of adrenal insufficiency. Congenital adrenal is hemodynamically stable, hydrocortisone is tapered to
hyperplasia (CAH) due to deficiency of 21-hydroxylase the physiological dose (10 mg/m2 / day). Fludrocortisone
or 3~-hydroxysteroid dehydrogenase and deficient acetate (0.1 mg/day) is added once hydrocortisone dose
steroidogenesis due to defective steroidogenic acute is <50 mg/m2 / day.
regulatory protein (StAR; causing lipoid CAH) are the Long-term management of adrenal insufficiency
chief causes in the neonatal period. requires lifelong replacement of glucocorticoids and
Secondary adrenal insufficiency is caused by congenital mineralocorticoids. Parents should be educated about the
malformations (holoprosencephaly, midline defects), need for increasing dose during periods of stress. Thr. dose
genetic defects or acquired insults (neurosurgery, tumor, of glucocorticoid should be increased 2-3 times in
radiation). This is usually associated with other anterior conditions of minor stress (fever and mild infection) and
pituitary hormone deficiencies as well. In secondary 4- 5 times in severe stress (severe infection or surgery).
adrenal insufficiency, mineralocorticoid function is These doses should continue throughout the period of
preserved, as ACTH does not regulate aldosterone stress. Patients with secondary adrenal insufficiency
secretion. Thus, salt-wasting is not observed. Prolonged require lower dose of glucocorticoids (6-10 mg/m 2 / day);
steroid treatment is associated with suppression of the mineralocorticoid replacement is not necessary.
hypothalamic-pituitary axis resulting in adrenal
insufficiency after discontinuation of medications. Again, Congenital Adrenal Hyperplasia
mineralocorticoid activity is preserved in these patients.
Congenital adrenal hyperplasia (CAH), a group ~f
Clinical features: Adrenal insufficiency presents with autosomal recessive defects in steroid synthesis, 15
slowly progressive lethargy, vomiting, salt craving, characterized by deficiency of adrenocortical hormones
fatigue, postural hypotension, hypoglycemia and episodes on one hand and excess of steroid precursors on the oth~r
of shock during severe illness. The concomitant presence (Fig. 18.12). CAH is the commonest adrenal disorder lil
of shock, hyponatremia, hyperkalemia and hemoconcen- childhood.
tration is characteristic of acute adrenal insufficiency and
warrants immediate steroid replacement. Primary adrenal 21-hydroxytase Deficiency
insufficiency is characterized by hyperpigmentation due 21-hydroxylase deficiency is the commonest form of CA~
to elevated levels of melanocyte-stimulating hormone. accounting for over 90% of all cases. This ' rder 15
· d iso d
Hyperpigmentation is present in sun-exposed areas such associated with diminished synthesis of the cortiso~~J:J
as elbows and palmar creases and areas that are normally - aldosterone. Low cortisol levels stimulate A
Endocrine and Metabolic Disorders js23 -
.-- ·Tabi8"1 e.20; eompanson-of common~ used steroid preparations
synthesis. Elevated ACTH level causes accumulation of
steroid precursors (e.g. dehydroepiandrosterone, Potency (compared Biological
Preparation
androSten~one and 17-hydroxyprogesterone). Depending to hydrocortisone) half-fife
on the seventy of enzyme deficiency, the disease forms a Gluco- Mineralo- Growth
spectrum of presentation as highlighted below. corticoid corticoid inhibitory
salt-wasting fonn: These patients are the most severely 1 1 1 6 hours
Hydrocortisone
affected and present in the neonatal period with 0.8 1.25 1.25 5 hours
Cortisone
viri}ization and salt-wasting. Abnormal genital appearance 8 8 hours
Prednisolone 4 0.25
should prompt the diagnosis in girls. Diagnosis is often
0 40 12 hours
Jllissed in boys as they lack specific clinical features. They Dexamethasone 20
present after second week of life with failure to thrive, 100 0.1 12 hours
Fludrocortisone 0.1
polyuria, hyperpigmentation and shock. Early diagnosis
is mandatory to prevent mortality. 21-hydroxylase in those with simple virilizing and non-classic forms. The
deficiency should be suspected in neonates with best method of diagnosing these patients is the estimation
ambiguous genitalia, polyuria, shock, recurrent vomiting of 17-0HP levels before and 60 minutes after an
and features of sepsis with negative septic screen. The intramuscular injection of ACTH (0.25 mg).
diagnosis is confirmed by measurement of blood levels
of 17-hydroxyprogesterone (17-0HP). If these tests are not Ma11ageme11t: These patients req~ire lifelong. steroid
available, the child should be managed empirically in the replacement therapy. Patients with salt-wasting and
lines of adrenal insufficiency. virilizing forms are treated with hydrocortisone (10-15
mg/m2 /day) and fludrocortisone (0.1 mg/ day). After
Simple virilizing form: A subset of patients with 21-
completion of growth and pubertal development,
hydroxylase deficiency (25%) synthesizes enough
synthetic glucocorticoid preparations (dexamethasone,
aldosterone to prevent adrenal crisis. These patients have
prednisolone) can be used (Table 18.20).
features of androgen excess in the form of virilization in
girls and peripheral precocious puberty in boys (Fig. 18.15).
Other Variants
Non-classic fonn: This disorder is associated with partial Enzyme deficiencies other than 21-hydroxylase deficiency
21-hydroxylase deficiency. Clinical manifestations are account for less than 10% of cases of CAH (Table 18.21).
related to mild hyperandrogenism that presents with Patients with 11-hydroxylase deficiency and 17-
hirsutism, acne and menstrual irregularity in adolescents. hydroxylase deficiency present with hypertension and are
Diagnosis: Diagnosis of the salt-wasting form is managed with hydrocortisone alone. Deficiencies of StAR
established by demonstration of extreme elevation of 17- and 3-hydroxysteroid dehydrogenase manifest as salt-
0HP levels (10000-20000 ng/ dL, normal <90 ng/ dL) in wasting crisis and require therapy with rnineralocorticoid.
presence of clinical and laboratory features of adrenal
insufficiency. 17-0HP levels are elevated to a lesser extent Suggested Reading
• Bajpai A, Menon PSN. Congenital adrenal hyperplasia. In: Gupta
P, Menon PSN, Ramji S, Lodha R, Eds. PG Textbook of Pediatrics,
second Ed. New Delhi; Jaypee Brothers, 2018; pp 2712-7.
• Brandao Neto RA, de Carvalho JF. Diagnosis and classification of
Addison disease. Autoimmune Rev 2014; 13: 408-11.
• Desai MP, Menon PSN, Bhatia V. Pediatric Endocrine Disorders,
3rd edn. Hyderabad: Universities Press, 2014; pp 221-267.
• Greaves RF, Jevalikar G, Hewitt JK, Zacharin MR. A guide to
understanding the steroid pathway: new insights and diagnostic
implications. Clin Biochem 2014; 47: 5-15.
• Shulman DI, Palmert MR, Kemp SF for the Lawson Wilkins Drug
and Therapeutics Committee. Adrenal insufficiency: Still a cause
of morbidity and death in childhood . Pediatrics 2007; 119: e484-94.
• Speiser PW, Azziz R, Baskin LS, et al. C o ngenital adrenal
hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine
Society clinical practice guideline. J Clin Endocrinol Metab 2010;
95: 4133-{>0.
• Storr HL, Chan LF, Grossman AB, Savage MO. Pediatric Cushing
Fig. 18.15: Congenital adrenal hyperplasia secondary to 21- syndrome: epidemiology, investigation and therapeutic advances.
hYdroxylase deficiency. Note the clitoral hypertrophy, Trends En'docrinol Metab 2007; 18: 167-74.
hyPerplgmentatlon and Increased rugosltv of the labial folds • Savage MO, Storr HL. Pediatric Cushing"s disease: management
9Mng a male appearance to the female genitalia issues. Indian J Endocrinol Metab 2012; 16: S171-5.
Endocrine and Metabolic Disorders
I s2a -
~
,
. EI
synth~sis. evated ACTI-I level causes accumulation of
Table 1e.20: Comparison ofcommo~ty used Steroid preparations
steroid pr~cursors (e.g. dehydroepiandrosterone
androstened~one and 17-hydroxyprogesterone). Dependin~
on the seventy of enzyme deficiency the disease forms a
spectrum of presentation as highlighted below.
Preparation
G/uco-
Potency (compared
to hydrocortlsone)
Minera/o- Growth
cortlcold cortlcold Inhibitory
Biological
half-life Ill
Saft-wasting fonn: These patients are the most severely
Hydrocortlsone 1 6 hours
affe.cte? and present in the neonatal period with
virilization and salt-w~s ting. Abnormal genital appearance Cortisone 0.8 1.25 1.25 5 hours
sh.ould prompt the diagnosis in girls. Diagnosis is often Prednisolone 4 0.25 8 8 hours
aussed m boys as they lack specific clinical features. They Dexamethasone 20 0 40 12 hours
presen~ after sec?nd week of life with failure to thrive,
Fludrocortisone 0.1 100 0.1 12 hours
polyuna, hyperpigmentation and shock. Early diagnosis
is ~a.ndatory to prevent mortality. 21-hydroxylase
deficiency should be suspected in neonates with in those with simple virilizing and non-classic forms. The
ambiguous genitalia,.pol~uria, shock, recurrent vomiting best method of diagnosing these patients is the estimation
and features of sepsis with negative septic screen. The of 17-0HP levels before and 60 minutes after an
diagnosis is confirmed by measurement of blood levels intramuscular injection of ACTH (0.25 mg).
of 17-hydroxyprogesterone (17-0HP). If these tests are not
Management: These patients require lifelong steroid
available, the child should be managed empirically in the
lines of adrenal insufficiency. replacement therapy. Patients with salt-wasting and
virilizing forms are treated with hydrocortisone (10-15
Simple virilizing form: A subset of patients with 21- mg/m2 /day) and fludrocortisone (0.1 mg/day). After
hydroxylase deficiency (25%) synthesizes enough completion of growth and pubertal development,
aldosterone to prevent adrenal crisis. These patients have synthetic glucocorticoid preparations (dexamethasone,
features of androgen excess in the form of virilization in prednisolone) can be used (Table 18.20).
girls and peripheral precocious puberty in boys (Fig. 18.15).
Other Variants
Non-classic form: This disorder is associated with partial
21-hydroxylase deficiency. Clinical manifestations are Enzyme deficiencies other than 21-hydroxylase deficiency
related to mild hyperandrogenism that presents with account for less than 10% of cases of CAH (Table 18.21).
hirsutism, acne and menstrual irregularity in adolescents. Patients with 11-hydroxylase deficiency and 17-
hydroxylase deficiency present with hypertension and are
Diagnosis: Diagnosis of the salt-wasting form is managed with hydrocortisone alone. Deficiencies of StAR
established by demonstration of extreme elevation of 17- and 3-hydroxysteroid dehydrogenase manifest as salt-
0HP levels (10000-20000 ng/ dL, normal <90 ng/ dL) in wasting crisis and require therapy with mineralocorticoid.
presence of clinical and laboratory features of adrenal
insufficiency. 17-0HP levels are elevated to a lesser extent Suggested Reading
• Bajpai A, Menon PSN. Congenital adrenal hyperplasia. In: Gupta
P, Menon PSN, Ramji S, Lodha R, Eds. PG Textbook of Pediatrics,
second Ed. New Delhi; Jaypee Brothers, 2018; pp 2712- 7.
• Brandiio Neto RA, de Carvalho JF. Diagnosis and classification of
Addison disease. Autoimmune Rev 2014; 13: 408-11.
• Desai MP, Menon PSN, Bhatia V. Pediatric Endocrine Disorders,
3rd edn. Hyderabad: Universities Press, 2014; pp 221-267.
• Greaves RF, Jevalikar G, Hewitt JK, Zach arin MR. A guide to
understanding the steroid pathway: new insights and diagnostic
implications. Clin Biochem 2014; 47: S-15.
• Shulman DI, Palmert MR, Kemp SF for the Lawson Wilkins Drug
and Therapeutics Committee. Adrenal insufficiency: Still a cause
of morbidity and death in childhood. Pediatrics 2007; 119: e484-94.
• Speiser PW, Azziz R, Baskin LS, e t al. Congenital adrenal
hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine
Society clinical practice guideline. J Clin Endocrinol Metab 2010;
95: 4133-60.
• Storr HL, Chan LF, Grossman AB, Savage MO. Pediatric Cushing
Fig. 18.15: Congenital adrenal hyperplasia secondary to 21- syndrome: epidemiology, investigation and therapeutic advances.
hYdroxylase deficiency. Note the clitoral hypertrophy, Trends Endocrinol Metab 2007; 18: 167- 74.
hYPerp!gmentatlon and increased rugoslty of th~ labial folds • Savage MO, Storr HL. Pediatric Cushing's disease: management
QMng a male appearance to the female genitalia issues. Indian J Endocrinol Metab 2012; 16: 5171-5.
--a;:;•
.,....;;:oo~ ...... ...
Essential Pediatrics
- 524 I ~
- - --Table 18.21:- Comparis on of common variants of congenital adrenal hyperplasia
I Enzymes
deficient
21 ·hydroxylase
Salt-wasting
Androgen
levels
High
Blood pressure
Low
Clinical presentation
Boys
Precocious
Girls
Ambiguity of
Laboratory
· diagnosis
17-0HP*
Treatment
Hydrocortisone
Fludrocortisone
puberty genitalia
Ambiguity of 17-0HP* Hydrocortisone
Simple virilizing High Normal Precocious
puberty genitalia
Hirsutism 17-0HP* Hydrocortisone
Non-classic High Normal Normal
Fludrocortisone
Ambiguity of DOC Hydrocortisone
11 P-hydroxylase High High/Normals Precocious
genitalia Spironolactone
puberty
Ambiguity of ACTH Hydrocortisone
3f3·hydroxysterold Variable# Low Ambiguity of
genitalia stimulation Fludrocortisone
dehydrogenase genitalia
test**
Highs Ambiguity of Delayed puberty DOC Hydrocortisone
· 11cx-hydroxylase/ Low
genitalia Fludrocortisone
17·1yase
StAR Low Low Ambiguity of Delayed puberty Low 17-0HP Hydrocortisone
genitalia Fludrocortisone
OBESITY Weiglit for height: This compares the child's weight to the
expected weight for his/her height and is useful in
The incidence of childhood obesity has increased rapidly
children below 2 years of age (see Chapter 2). Weight for
in the last decade. The prevalence of overweight and/ or
height more than 120% is diagnosed as obesity.
obesity in Indian children is around 20% posing significant
risk of lifestyle diseases in future. Skinfold tltickness: Skinfold thickness measured over the
subscapular, triceps or biceps regions is an indicator for
Criteria for Diagnosis of Obesity subcutaneous fat. Age specific percentile cut-offs should
Obesity implies excessive fat and not merely excess weight. be used with values more than 85th percentile being
As methods of measuring body fat are cumbersome and abnormal.
expensive, several clinical and anthropometric parameters
Waist circumference and waist hip rati o: Waist
are used as markers of obesity.
circumference is measured at the minimum circumference
Body mass index: Body mass index (BMI) is the most widely ~etween the iliac crest and the rib cage. Hip circumference
used parameter to define obesity. It takes into account is measured at the maximum protuberance of the buttocks,
weight as well as the height. It is calculated by the formula: and the waist hip ratio (WHR) may be calculated from
these values. Waist circumference itself is a satisfactory
BMI =Weight (kg) + height (m2)
marker of abdominal adiposity, a risk factor for me tabolic
Children with BMI more than 85th percentile for age and cardiovascular effects of obesity. Waist circumference
are considered overweight while those with more than greater than 75% is a risk factor for metabolic
95th percentile for age are obese. BMI is a good indicator complications. WHR is probably a more refined method
of body fat but is unreliable in short muscular individuals. but is not age-independent; norms for Indian children are
BMl greater than 99th percentile (120% of 95th percentile) not available.
implicate severe obesity. The cutoffs for obesity should
take into consideration the local population. As the aim Etiology
of assessing BMI is to identify individuals at risk for
In most children with obesity, environmental and the
metabolic complications, lower BMI cutoffs h ave been
hereditary factors play the major role. Underlying etiology
recommended for Indian adults (23 kg/m2 for overweight
is identified in a few cases (<1 %) . The ca uses of childhood
and 27 kg/m2 for obesity). Thus the use of CDC charts
obesity are classified in Table 18.22.
would underestimate the problem of obesity in Indian
children and IAP 2015 growth charts should preferably Constitutional obesittp Most children with obesity do n?t
be used for defining obesity. have an organic cause. This is caused by imbalance Ul
Endocrine and Metabolic Disorders
I s25 •
Drugs: Commonly used drugs associ·ated with obesity ·. fig. 18.16: Acanthosls nlgrlcans on the back of neck in a girl
include corticosteroids, antipsychotics (o 1anzapme, with obesity
-526 Essential Pediatrics
Table 1 8.26:· ~tions of obesity Rcsi•ir11tory systt•m: Obcsc children nre nt risk of
CotrJpijca00n.s rcspirntory distress nnd bronchinl nsthmn. Obesity t
lnsu&t reS:stance. type 2 ciabetes. metabolic
predisposes to the development of obstructive sleep npnca 1
and hypovcntilntion syndrome.
SJTldrome. h~iperandrogenism
Hypertens.ion. dyslip«remia. atherosclerosis G11stroit1ft•sti1111l syslt'm: Obesity is llSSocintcd with
Non-alcoholic fatty liver disease, gall· gastroesophngeal rcnux discnse and non-<1lcoholic fotty
stones. gastroesophageal reflux liver disease. Fatty liver is present in 40'Y,, of children with
Bl~nrs cfrsease, slipped capital femoral obesity but elcv<ttcd serum trnnsaminascs occur only in
eptphysis, fractures 25% of thl'Se children. Gallslont•s nrc noted in 2% children
Obstructive sleep apnea, hypoventilation with obesity. R<tpid weight fluctuations arc associated
syn<irome with the gallstone disease. Gallstone should be suspected
Benign intracranial hypertension
in an obese child with recurrent abdominal pain, jaundice,
nausea and intoler<tnce to fatty foods.
fndDcrine system: Endocrine complications are the most Psyclwlogicnl issues: Obesity is associated with increased
Important ad\-eTSe effects of childhood obesit\-. Central prevalence of mood disorders. This represents intrinsic
to this~ the de\·elopr:r'ent of insulin resistance caused by effects of obesity and psychological effects of bullying.
m-er:.l'ill of fat and its deposition in lh·er and skeletal
muscle. ~resistance predisposes to deYelopment of Assessment of Complications
tj-pe 2 diabetes, polycystic O\·arian disease, metabolic
The high incidence of complications in obese children calls
~&ldrom~ an~ non-alcoholic fatty li\·er disease. Hyper-
for regular follow-up screening. Investigations should
androgerusm IS a common feature in obese girls. Obesity include a baseline oral glucose tolerance test using blood
has also been associated \\ith accelerated growth, skeletal sugar leYels fasting and 2 hours after 1.75 g/kg glucose
maturation and early puberty in girls.
(maximum 75 g), lipid profile and liver hmction tests. Age
Cardiovascular system: Obese children haYe a higher pre- appropriate cutoffs should be used for these investigations
valence of dyslipidemia, hypertension and atherosclerosis. (Table 18.27). These tests should be repeated every 3 years,
Importantly hypertension may be masked, requiring if normal. Fasting insulin has limited role and is not
repeat blood pressure measurements. Childhood obesity routinely required. Mildly elevated liver transaminases
is associated with increased risk of adult coronary disease. are common in obese children; persistent elevation beyond
twice the upper limit indicates non-alcoholic steato-
Central nervous system: Benign intracranial hypertension hepatitis. Children with elevated transaminases should
is common in children with obesity and presents with undergo ultrasound abdomen and work-up for other
headache and vomiting. causes of hepatic dysfunction (hepatitis Band C, Wilson
Orthopedics: Obese children have a higher risk of flat foot, disease and autoimmune hepatitis). Sleep studies may be
Blount disease (tibia vara), fractures, genu valgum and required in the presence of snoring, daytime somnolence
osteoarthritis. The most debilitating complication is or lethargy.
slipped capital femoral epiphysis. This presents with dull
aching pain in knee, hip or groin with abnormal gait. Management
Blount disease presents with progressive bowing of legs Management of childhood obesity is challenging with
and knee pain. X-ray of knee and hip should be done in major impetus on lifestyle measures (Fig. 18.19). Specific
obese children with recurrent pain in hip or knee or management is available for only a few situations. Diet,
abnormal gait activity and behavioral measures are the cornerstone of
I Body mass index I like dancing, sports and running should made to en
· d ai·1y. We1g
· h t bearing exercise
sure
I a minimum of 30 minutes
+
2-3.5 sos >3.SSDS
+ and over-regimented schedule should be avoided. s
Assess for complications
lr
Specific Management
Complications or Specific treatment should be initiated in children With
Insulin resistance hypothyroidism, GH deficiency and Cushing syndrom
Children with mildly elevated TSH level do not nee~
Lifestyle modification Lifestyle modification/ treatment. Obese children with Prader-Willi syndrom
Diet, physical activity Add metformin/
statin, if indicated and growth failure may benefit from GH therapye
Octreotide is effective in hypothalamic obesity whiJe th~
No improvement use of leptin is reserved for leptin deficiency.
No improvement More intensive diet
New complications _ _ __., Treatment of Complications
control/metformin/orfistat.
Surgery, if indicated. Complications should be treated early to avoid long-term
Fig. 18.19: Approach to management of obesity. SOS standard adverse effects. Metformin is indicated in children with
deviation score insulin resistance and type 2 diabetes, non-alcoholic fatty
liver disease and polycystic ovarian disease. Statins are
therapy; measures such as drug therapy and surgery are the drug of choice for children with persistent
reserved for morbid cases. dyslipidemia. Treatment of non-alcoholic fatty liver
disease includes the use of metformin, vitamin E and
Th~ ~~a~ement of obesity is a challenge, requiring
pioglitazone. Girls with polycystic ovarian syndrome may
mul~1-d1s_c1plmary approach involving physicians,
benefit from lifestyle modifications, metformin, oral
nutnti?n~sts and physical trainers. The goal is to bring
contraceptives and antiandrogens. Medroxyprogesterone
BMI within the normal range for age and gender. Excessive
acetate is beneficial in children with obesity-
an? rapid weight loss adversely affects the growth of the
child and should be avoided. In most children, weight hypoventilation syndrome while continuous positive
airway pressure may be used in obstructive sleep apnea.
stabilization is the initial aim; weight loss should not
exceed 1 kg per month. The child and parents are
Medical Management tor Obesity
counseled that there is no quick fix solution for obesity.
The focus is on changing the lifestyle of the child without Orlistat is the only drug approved for use in children with
recourse to drugs and surgery. obesity. The drug inhibits gastric lipase resulti ng in
red_uce~ absorption of fat with modest weight loss. The
Lifestyle Measures ma1or side effects are abdominal pain, bloating, steil torrhea
and leakage of oil. The medicine should be combino?d with
The cornerstone to management is lifestyle measures. The
fat-soluble vitamins. Newer agents include MC4 receptor
whole family is encouraged to follow a healthy lifestyle
modulators, GLPl analogs and endocannabinoid agonists.
as a unit; focusing on the child alone is often
counterproductive. Surgical Management
Nutritional therapy: The child should be advised to stick Bariatric surgery is considered in severe obesitv when
to regular meals. Skipping breakfast and snacking in oth~r ~eas:ires fail. The intervention is preferr~d after
between meals should be discouraged. The caloric intake achievmg fmal height to avoid potential adverse ~owth
should be reduced by 20%. Overzealous restriction and effects. Bariatric surgery is a major surgical under~aJ<ing,
fad diets are not recommended. Food pyramid and 'traffic and should be viewed as a potentially life-saving and not
light' approach for diet may be used to highlight healthy just a cosmetic procedure. Patients need to adhere to strict
eating pattern. Special emphasis is laid on fixed portion dieta~y r~striction for life. Laparoscopic adjustable
size, decreased junk food consumption, avoiding bandmg is the recommended procedure in children·
television viewing while eating, and increased fruit Malabsorptive procedures and gastric sleeve are not
consumption. recommended for children.
I
cafe au lait spots), skeletal (multiple fibrous dysplasia) and
. Gon~dot~~~ln~ependent or central precocious puberty endocrine abnormalities (hyperthyroidism, rickets and
. Idiopathic GH excess). Precocious puberty occurs at an early age and
Tumors: Hamartoma, pituitary adenoma, craniopharyngloma, is rapidly progressi~e. Prolonged untreated prim~ry
glioma hypothyroidism may induce early puberty due to action
Infections: Neurotuberculosis, meningitis of TSH on FSH receptor. Delayed bone age and growth
Injury: Head trauma, neurosurgery, cranial irradiation are characteristics.
Malformation: Arachnoid cyst, hydrocephalus, septo-optic
dysplasia Evaluation
.' Gonadotropln-lndependent or. peripheral precocious Aims of evaluation include confirmation of diagnosis,
puberty · · identification of underlying etiology and determination
Hypothyroidism of prognosis and treatment (Fig. 18.20).
Ovarian estrogen: McCune-Albright syndrome, cyst, tumor,
aromatase excess Clinical: History should include the onset, progression
Adrenal estrogen: Estrogenic adrenal adenoma and extent of puberty. Exposure to steroids, estrogens and
Exogenous estrogen exposure androgens should be enquired. Family history of
. - precocious puberty and early menarche points towards
Incomplete v:arlants
idiopathic central precocious puberty. Features of
Isolated thelarche hypothyroidism should be assessed. Advanced growth is
Isolated pubarche (adrenarche) characteristic of precocious puberty; growth retardation
Isolated menarche indicates hypothyroidism or concomitant GH deficiency.
Gonadotropin-independent precocious puberty (peri- Examination of vaginal mucosa for estrogen effect
pheral precocious puberty) is rare and usually caused by provides clues regarding the pubertal status of the patient.
estrogenic ovarian cysts. Fluctuating pubertal development Red, glistening vaginal mucosa suggests lack of estrogens
and early vaginal bleeding (due to hyperestrogenic state) while pink mucosa with mucus is indicative of estrogen
is common. The condition is usually self-resolving and effect. Abdominal examination for adrenal or ovarian mass
there is no need for treatment. Recurrent ovarian cysts should be done. Features of McCune-Albright syndrome
should raise the possibility of McCune-Albright syndrome, include cafe au lait spots, polyostotic fibrous dysplasia,
a somatic activating mutation of stimulatory G protein, bony deformities and polyendocrinopathy.
•
Retarded
IExclude hypothyroidism J
Normal
i i
•
LowLH Elevated LH
I
i
Prepubertal LH response Pubertal LH response
•
Gonadotropln-lndependent pp •
Gonadotropln-dependent pp
Ultrasound adrenal and ovary MRI brain
Bone scans for fibrous dysplasia
Management
Management of central precocious puberty includes
treatment of underlying pathology and GnRH analog
therapy. GnRH analog should be continued till the age of
12 years. CAH is managed with hydrocortisone and
fludrocortisone. Surgery is the treatment of choice f~r
adrenal and testicular tumors, while radiotherapy 15
effective in hCG-secreting tumors. Arornatase inhibitors
and antiandrogens are indicated in testotoxicosis.
Delayed Puberty
Delayed puberty is more common in boys than in ~r15·
Fig. 18.21: Central precocious puberty secondary to
hypothalomlc hamartoma Most children with delayed puberty have consti·tutlona
1
Endocrlno nnd Motobollo Dl1ordor• 833
Prococlou11 pulJorly -
Atl8ons tho oxlonl, lotillculnr olzo
,-- Tablo 18:31: Elfofogy or cJtjfnyod puborty In gfrfo - 1
-- ,--
Boriollno LH, FSI I
-Propubortol LH lovols
- - +___ -·--
'Hypogonadotropfo hypogonadl1m
Tron9/ont
Syotomlc dloorcJoro: f~orwl folluro, llvor dlrioaoo, collac dl30lJM,
J ronal tubular oclcJoolo, cyollc flbroolo
GnRH o llrnul1p10~'...!.os~J Nulrlllonol dloorcJoro: MalnlJlrltlon, onoroxla norvoaa
__+__ _ i
EncJocrlno dloordoro: Mypolhyroldlr;rn, hyporproractfnomla, typo
1 cllobotoo
' Propubortnl LH rosponso r ronpo~iiio-]
I- - - -:i- - --.J
Adronol lmoglna
Puborlol LH
-- t - -
Pormonont
lsolatod hypogonadotroplc hypooonodlem
+ i IOonndotropln·
dopondont
Gonellc: KAL 1, GnAH rocoptor, LH, FSH, DAX1 mutatlone
Dyemorphlc oyndromoa: CHARGE, Prador·Willl, Lauronoo·
Normol lmoglng Moss loslon - t Moon-Bardol·Blodl
i [ Mm br~-.1 Multlplo pituitary hormono doflcloncloo
JACfH stlmulallon lost L&fuinol tu'!'or I Malformations: Holoproeoncophaly, oopto·optrc dyBplasla,
I mldllne dofocto
t t Genetic disorders: PROPf, LH gono dolotrono
Normol 17-0HP lovols High 17-0HP Brain tumors: Cranlophoryngloma, germlnoma, glloma
+
Check hCG le~ l-cA6 Brain Injury: Surgery, Infection, radlatlon, trauma
lnflltrallve disorders: Hlatlocytosla, autolmmune disorders
I Hypergonadotroplc hypogonadlam
t t
Normal High Gonadal dysgenesls: Turner syndrome, SRY deletion, tr1somy
18, 13, 21
LH receptor study hCG-aecrotlng tumor Steroldogenlc defects: StAR, 17u.-hydroxy1Mo, 17f~hydroxy
CT brain, chost and abdomon sterold dehydrogenaae or aromatase deficiency
Ovarian Insults: Surgery, radiation, alkylating agents, Infections
Fig. 18.23: Approach to precocious puberty Jn boys. ACTH Autoimmune ovarian failure: Autoimmune polyendocrinopathy
adrenocortlcotroplc hormone; CAH congenital adrenal Gonadotropln resistance: LH and FSH receptor mutations
hyperplasia; CT computed tomography; FSH folllcle-stlmulatlng
Isolated amenorrhea
hormone; GnRH gonadotropln-releaslng hormone; hCG human
chorlonlc gonadotropln; LH lutelnlzlng hormone; MRI magnetic Structural malformations: Mullerlan agencsls, vaginal septum,
resonance Imaging; 17·OHP 17-hydroxyprogesterone lmperlorate hymen
Inefficient androgen action: Complete androgen insensitivity
syndrome
delay emphasizing the need for watchful monitoring and DAX1: Dosage sensitive sex reversal; FSH: Follicle-stimulating hormone;
conservative approach. GnRH: Gonadolropln-releasing hormone; LH: Lutelnizing hormone;
KAL 1: Kallman syndrome gene 1; SIAR; Steroidogenlc acute regulatory
protein; SRY: Sex determining region on Y chromosome
Delayed Puberty In Girls
Delayed puberty in girls is defined as Jack of secondary by ovaries and elevated gonadotropin levels. Causes
sexual characteristics by the age of 13 years. Absence of include Turner syndrome, ovarian failure and enzymatic
menarche by the age of 16 years, or S years after onset of defects in estrogen synthesis.
puberty indicates pubertal delay.
Evaluation
Etiology Goals of evaluation include identification of constitutionaJ
Delayed puberty may be caused by defects in the delay, organic etiology requiring neuroimaging and
hypothalamic-pituitary axis, ovaries or genital tract decision regarding treatment.
(Table 18.31). Defects in the hypothalamic-pituitary
Clinical: Family history of delayed puberty provides a
axis are associated with low gonadotropin levels
clue to constitutional delay in puberty. Patients are
(hypogonadotropic hypogonadism). This may be related
screened for chronic systemic or neurological diseases,
to reversible causes such as systemic diseases,
Turner syndrome or hypothyroidism, and poor olfactory
malnutrition, eating disorders, hyperprolactinemia and
sensation. Amenorrhea with normal secondary sexual
hypothyroidism. Irreversible defects include destruction
characteristics indicates anatomical defects.
of the hypothalamic-pituitary axis by infection, surgery,
radiation or tumor. Defective smell sensation, low GnRH Investigations: Workup is directed towards screening for
levels and hypogonadotropic hypogonadism characterize systemic disorders (liver, renal or gastrointestinal disease),
l<allmann syndrome, a neuronal migration defe_ct due to followed by estimation of FSH levels and karyotype.
mutation of KAL1 gene. Hypergonadotrop1c hyi:>o- Steroidogenic defects are likely, if karyotype and pelvic
gonadism is associated with defective estrogen production ultrasound are normal. In patients with low /normal FSH
·-
- ~ ' ---------~Es~sec=n~tiaJ~Pedi~
aa~trlcs~-----------
~~e:'~t "'hble t&.32: ~ ol delayed puberty In boys
2cttE ~seuic ·1h:e!.:s ~.ii os:r=e- -~ hypogonadlsm
a:i.a:cu :::er:. -ew.e-~
Tra~-S-u!
I Qmse.:.t"i'~ d€ta.~· cf puberty and growth
• ~~ci~~ R~ ~re. tr:erdisease, celiacdiseas~,
H~~
~,:::u::e ="<=ran frs.rit ; renal ruool'.ar ~ ~-stic fibroSts
~Ct?~ N~-..'a?al en~ Malnutrition. anorexia nervosa. bulimia
T
00."\"CSR
~ cf'~ ~,xithyroidism, hyperprolactinemia, type
~
&el'.s::::sa:u ,
0-5 fr::a;i1'"-g
NCc::a
t!I~ ::e"·ts
k:t:::ir::r:l:r eoo=i~
I t QSabetes m~
Delayed puberty
•
Screening Investigations
Gonadotropln
Low High
Clinical follow-up Exclude testlcular Insult
GnRH/hCG test Karyotype
Response No response
CDPG Permanent HH
MRI head
Low
hCG test
Testicular biopsy
Low High/normal
5cx-reductase defect partialAIS
Investigations: Initial step includes estimation of LH, FSH mosaic forms like 45X/ 46XX and 45X/ 46XY are also
and testosterone levels. Elevated gonadotropin levels observed. Premature atresia of ovarian follicles and
(hypergonadotropic hypogonadism) should be followed bilateral streak gonads may be present.
by karyotype (Klinefelter syndrome) and evaluation for
biosynthetic defects. Boys with low LH and FSH levels Clinical Features
may have constitutional delay in puberty or h ypo- Short stature is a frequent finding. Turner syndrome is
gonadotropic hypogonadism. They may be distinguished identified at birth by presence of lymphedema, cystic
by hCG stimulation test or GnRH s timulation test hygroma and left-sided obstructive cardiac lesions. Features
(Fig. 18.26). However, these tests are nondiscriminatory in childhood include cubitus valgus (wide carrying angle),
in most cases and follow-up after a course of testosterone shield chest with widely spaced nipples, web neck and short
is the best strategy. Patients with hypogonadotropic fourth metacarpal (Table 18.33). Cardiac associations such
hypogonadism should undergo. eva~uation of hypo- as coarctation of aorta, mitral valve prolapse and aortic
thalamic-pituitary axis and neurormagmg. stenosis are common. Renal m alforma tions such as
horseshoe kidney, duplication of renal pelvis and agenesis
Management may be present. Endocrine associations include hypo-
Testosterone treatment should be deferred till the age of thyroidism and diabetes mellitus.
14 years and bone age of 13.5 years. Boys with .suspected
constitutional delay in puberty should receive three-
monthly injections of testosterone enanthat.e (100 mg~. This Tabla 18.33: Pointers to the diagnosis of !urn~r syndrome
should be repeated, if adequate response is not achieved . Age.group Features . ,
1
Serum testosterone levels should be estimated three Intrauterine period Increased neck translucency, cystic
months after the last dose of the drug. Low testosterone hygroma
levels indicate hypogonadotropic hypogonadism and the Infancy Cystic hygroma, lymphedema,
need for continued treatment. coarctation of aorta, partial
anomalous pulmonary venous
Turner Syndrome return (PAPVR)
Turner syndrome is the most i~p?rtant ca~se of Childhood and Growth failure, hearing defect,
hypergonadotropic hypogonadism m girls. The disor~er adolescence delayed puberty, skeletal abnor-
affects 1 in 2500 newborn phenotypic females. These girls malities
present with short stature, classical phenotyp.e and Adulthood Secondary amenorrhea, infertility
delayed puberty. While most common karyotype is 45X,
-536 I Essential Pediatrics
---...__
,..,..-~- ...----
I_ Table 18.34: Associations ofTumersyndrome
• .._ . ~ .I -
Intervention
..
System Association
Growth Growth failure GH, oxandrolone
Delayed puberty, secondary amenorrhea, infertility FSH estimation at 12 years, hormone replacement
Puberty
Cardiovascular Coarctation of aorta, bicuspid aortic valve, partial Four limb blood pressure, ECG, ECHO at baseline, MRI
system anomalous pulmonary venous return (PAPVR), at 1B years, imaging every 5 years
aortic dissection
Ear Otitis media, conductive and sensorineural hearing loss Hearing assessment, otoscopic examination, hearing aid
Eye Strabismus, ptosis, color blindness Fundoscopy
Orthopedics Scoliosis, lordosis, reduced cortical density, congenital Orthopedic review
dislocation of hip
· Renal system Collecting duct abnormality, horseshoe kidney, Ultrasound kidney
positional abnormality
Autoimmune Hypothyroidism, celiac disease Thyroid function, tissue transglutaminase antibodies
disorders
Skin Pigmented nevi Monitoring for size
Gonadal differe11tiatio11: Germ cells arise from the • Table 18.35: Karyotype based classification of disorders of i •
coelomic epithelium of hindgut and migrate to the gonadal · sex differentiation (DSD) : I
ridge at 4-6 weeks of gestation. These cells combine with 46,XX DSD
somatic cells to give rise to the bipotential gonad. A Androgen excesss
transcriptional factor present on the Y chromosome called Congenital adrenal hyperplasia
the sex-determining region of the Y chromosome (SRY) is 21-hydroxylase deficiency
one of the most important regulators of sexual 11 ~-hydroxylase deficiency
differentiation. SRY acts in conjunction with other genes
3~-HSD deficiency
like Wilms tumor gene 1 (WTJ), SOX9 (a transcription
POR deficiency
factor on X chromosome) and dosage-sensitive sex reversal
Placental aromatase deficiency
(DAXl) gene to induce testicular development. In the
Maternal virilizing tumors
absence of SRY, the bipotential gonad develops into ovary.
Maternal ingestion of androgenic drugs·
Genital differe11tiatio11: Following development of testis, Abnormal gonadal developments
antimi.illerian hormone secreted by Sertoli cells induces Ovotesticular DSDs
regression of Miillerian ducts. Testosterone produced by 46,XX testicular DSD (SRY+, SOX9 duplication)
Leydig cells is responsible for sustenance of Wolffian ducts. 46,XY DSD
Dihydrotestosterone (DHT), produced by action of Sa- Disorders of androgen synthesis or actions
reductase on testosterone, is responsible for male external LH receptor mutationss
genital development (scrotal fusion and development of
Congenital adrenal hyperplasia
corpus spongiosum and penile corpus cavemosa).
StAR deficiency
Feminization is the default process of sexual
3~-HSD deficiency
development. Jn the absence of antimi.illerian hormone
17-hydroxylase/1 7,20-lyase deficiency
and testosterone, Miillerian ducts differentiate into
POR deficiency
fallopian tubes, uterus and the upper two-thirds of the
vagina. Labioscrotal swellings and urethral folds do not 17P-HSD deficiency
fuse and give rise to labia majora and minora, respectively. 5cx-reductase deficiency: Types I and II
The genital tubercles form the clitoris while canalization Androgen insensitivity syndrome (AIS): Complete or partial
of the vaginal plate creates the lower portion of the vagina. Smith-Lemli-Opitz syndrome
Prenatal exposure to androgens may lead to labioscrotal Abnormal gonadal development
fusion, while exposure thereafter usually causes Gonadal dysgenesis: Complete or partial
clitoromegaly alone and no labial fusion. Gonadal regression
Ovotesticular DSD
Classification Other conditions
DSD may be caused by defects in gonadal differentiation Persistent MOllerian duct syndrome
(gonadal dysgenesis), androgen production (increased in Sex chromosome DSD
females and reduced in males) or action (androgen 45,X (Turner syndrome and variants)
insensitivity syndrome) (Table 18.35). 47,XXY (Klinefelter syndrome and variants)
Increased androgen production in girls: Excess androgen 45,X/ 46,XY (mixed gonadal dysgenesis, ovotesticular DSD)
production during the critical period of fetal development 46,XX/46,XY (chimeric, ovotesticular DSD)
may result in masculinization of a female. These disorders HSD: Hydroxysteroid dehydrogenase; POR: P450 oxidoreductase;
are the commonest form of DSD. Congenital adrenal SIAR: Steroldogenic acute regulatory protein
hyperplasia should be excluded in all children with DSD.
21-hydroxylase deficiency is characterized by deficiency
of glucocorticoids and mineralocorticoids with elevated Inefficient androgen action i11 boys: These disorders result
androgen levels. Delay in diagnosis could be fatal, from decreased production, activation or action of
underscoring the importance of early diagnosis. llP- androgens. Androgen insensitiv ity syndrome (AIS)
hydroxylase deficiency, 3P-hydroxysteroid dehydrogenase previously referred to as testicular feminization syndrome,
deficiency and P450 oxidoreductase deficiency are the an X-linked disorder of androgen action, is the commonest
other forms of CAH that present with virilization. cause and is characterized by resistance to androgens. AIS
Transplacental androgen exposure due to maternal forms a spectrum ranging from a normal fema le to a boy
medications or hyperandrogenism may lead to virilization with hypospadias, to a male with infertility. Complete
in newborns. These disorders are readily identifiable by androgen insensitivity presents in the neonatal period as
history of virilization in mother. Rarely aromatase a girl with inguinal mass and primary amenorrhea in older
deficiency may be associated with virilization of mother girls. Pubic and axillary hair is sparse or absent. Mi.illerian
during pregnancy and DSD in the newborn. structures are absent. High DHT levels are diagnostic. 5a-
- 5381 Essentlal Pediatrics
reductase deficiency is associated with reduced DHT Tabte 18.36: Cllnlcal_p.o ln(;s to~etiology of disorders of
production. These children virilize during puberty due sexual differentiation (DSD)
to increased testosterone levels. High testosterone and low Pointer Likely diagnosis
DHT levels are diagnostic. Testosterone biosynthetic Congenial adrenal hyperplasia, SF1
Pigmentation
defects include deficiency of StAR, 3P-hydroxysteroid defect, StAR defect
dehydrogenase, 17a.-hydroxylase and 17P-hydroxysteroid Smlth·Lemell·Optlz syndrome
Polydactyly
dehydrogenase enzymes. Diagnosis requires estimation Skeletal dysplasla SOX9 defect
of testosterone precursors and basal and hCG-stimulated Genital asymmetry Mixed gonadal dysgenesis,
testosterone and androstenedione levels. ovotestlcular DSD
Hypertension 11 ~-or 17a·hydroxylase defect
Disorders of got1adal differentiation: These disorders are
associated with abnormal gonadal development. The Hemihypertrophy WT1 mutation
gonad is usually streak (no functional gonadal tissue). Renal failure Denys-Drash syndrome
Combinations of partially functional testis or ovary or Genital examination: The most important step is
ovotestis may be observed. SRY gene deletion results in
identification of gonads. Bilaterally rounded structures
normal female phenotype with 46,XY karyotype. below the inguinal canal are most likely testis. Unilateral
Mutations in genes involved in the testicular differentiation
gonads are suggestive of mixed gonadal dysgenesis. The
(WTl, SOX9, steroidogenic factor 1 and DAX1) are other
labioscrotal region should be evaluated for the extent of
causes of 46,XY gonadal dysgenesis. These disorders are
fusion (Fig. 18.28). Miillerian structures may be confirmed
associated with renal (WT1 mutation), skeletal (SOX9) and
by rectal examination. The length of phallus and number
adrenal abnormalities (DAXl). 46,XY gonadal dysgenesis
of openings in the urogenital region should be recorded.
is associated with risk of development of gonadoblastoma.
Asymmetrical labioscrotal region is suggestive of gonadal
Asymmetric gonadal location may result in asymmetric
dysgenesis or ovotesticular DSD. The genitalia should be
genital appearance. 46,XX gonadal dysgenesis is usually
caused by SRY translocation and presents as normal staged according to the classification proposed by Prader
appearing male. Ovotesticular DSD, the new term for true from grades I to V, with grade I representing female with
hermaphroditism, is characterized by the presence of both clitoromegaly and V male with cryptorchidism.
ovarian and testicular tissue in the same individual. Investigations: Initial investigations should incl ude
karyotyping, estimation of blood levels of electrolytes and
Evaluation 17-0HP and pelvic ultrasound. Fluorescent in situ
Detailed workup for DSD is indicated in the infants with hybridization (FISH) can be used to confirm the pres.:nce
genital ambiguity, girls with inguinal masses (probable of Y chromosome. Identification of Miillerian stnKrures
AIS), boys with cryptorchidism (probable 21-hydroxylase is an important part of evaluation of ambiguous geniulia.
deficiency) and penoscrotal h ypospadias (probable
undervirilization disorder) and adolescent girls with
amenorrhea (probable AIS) . 21-hydroxylase deficiency
should be excluded by estimating blood electrolytes and
levels of 17-0HP.
Clinical: Family history of genital ambiguity is suggestive
of genetic disorders such as 21-hydroxylase deficiency or
androgen insensitivity syndrome. CAH is likely, if there ....,
~
Management Etiology
Management involves parental counseling, decision about Most children with undescended testis do not have an
sex of rearing, timing of surgical correction and identifiable underlying cause. Endocrine causes, account
gonadectomy. for only a small proportion of boys with undescended
testis. The possibility of salt-wasting 21-hydroxylase
Parental co1111seli11g: Dirth of a child with DSD generates deficiency presenting with sex reversal should be
significant parental anxiety and stress. The most important considered in newborns with bilateral cryptorchidism.
aspect of counseling is reassurnnce of parents that the child Undescended testis may be associated with hypo-
is healthy and the condition is amenable to surgical and/ pituitarism, dysmorphic syndromes and disorders of
or medical treatment. Gender specific connotation (his or androgen production and action.
her, testis, ovary) should be avoided and neutral terms like
gonads and phallus be used. Future implications regarding Evaluation
sexual and fertility prospects should be discussed. It is important to differentiate true undescended testis
Decision about gender of rearing: Gender assignment from retractile or ectopic testis due to therapeutic and
should depend on the potential for future sexual and prognostic implications (Fig. 18.29). Poorly developed
reproductive function, anatomical status, feasibility of scrotum and inability to bring down the testis to the scrotal
reconstructive surgery and social acceptance and norms. sack suggests true undescended testis. Retractile testis is
Girls with virilization disorders usually have potential for an otherwise fully descended testis that has an active
fertility and should be reared as females. Individuals with cremasteric reflex, which retracts it into the groin.
Undescended testis
Present Absent
Assess scrotal development hCG test
..
Normal
Undescended testis
..
Negative
l Anorchla I
r ···-:-· --·-·
• f • - - -.. · • '"fabie·1a.39: Differenti~iing features of common causes of diabetes in child re~
i Feature Type 1 diabetes mellitus Type 2 diabetes mellitus Maturity onset diabetes of the
! '
young (MODY)
.Age at onset Any age; most common Post-pubertal; adults Post-pubertal; adults and
in children and adolescents adolescents
Onset of disease Acute Insidious Insidious
'Diabetic ketoacidosis at onset 3Q-60% 5-25% Less than 5%
Family history of diabetes 5-10% 75-90% 100%
Obesity Around 20% More than 90% Unusual
Acanthosis nigricans Absent Usually present Absent
Insulin requirement Universal Variable Variable
'
C-peptide levels Low High, normal Low-normal
I .
Insulin sensitivity Normal Low Normal
Islet cell antibodies 40--70% Unusual Negative
, Management Insulin Diet, metformin Diet, sulfonylurea
(ICA). These antibodies usually ~redate the. clinical
the initial stage of type 2 diabetes and autoantibodies are
presentation of insulin-dependent diabetes melhtus by a
positive in only 60% of Indian children with type 1
diabetes. fewmOnths or years. This suggests .thatf they
h
play a major
d'
1 during the initial pathogenesis o t e isease. The
Type 1 Diabetes Mellitus ~~=valence of antibodies in newly diagnosed Indian
children with type 1 diabetes is substantially lower.
Type 1 diabetes is the commonest form of childhood
diabetes characterized by insulin deficiency due to
Cl/n/cal Features
damage to beta cells of pancreas. The disorder requires
lifelong insulin replacement. Children and adolescents usually present with symptoms
of diabetes that are ongoing for a month or two prior to
Epidemiology seeking physician's contact, with an acute increase in
There is a significant geographic variation in the incidence symptoms over the previous we~k. Sympt?ms of t~p~ 1
of type 1 diabetes. Scandinavia has the highest incidence, diabetes include polyuria, noctuna, enuresis, polydipsia,
with Finland having the incidence of 35/100,000/year. recent weight loss, polyphagia and fatigue. Recent acute
Indian data suggest an incidence of 10.5/100,000/year. infection is often noted at presentation. Unfortunately,
Type 1 diabetes can occur at any age but has two these symptoms are often ignored resulting in delayed
discernible age peaks of higher incidence. The first peak diagnosis.
occurs around 5 to 7 years is related to exposure to viral
infections, while the second peak around puberty is linked Course of Illness
to increase in GH and sex steroids. Most children respond to insulin therapy. Once insulin is
initiated, blood sugars gradually decline. Often, after
Pathogenesis around a week of insulin therapy, the need for exogenous
Children born to parents with type 1 diabetes have a insulin declines, due to a transient recovery of insulin
higher risk of developing the disease. The risk is higher, secretion. This phase is called the "honeymoon phase of
if the affected parent is father (7% compared to 4%, if diabetes". Some children may be completely insulin-free
mother is affected). If a sibling is affected, the risk is 6% during this time. This phase lasts from a few days to a
when the onset is before 10 years of age and 3% thereafter. month, and rarely to one year. The need for insulin
The role of heredity is less significant in type 1 diabetes gradually increases till such time when the pancreas can
compared to type 2. In studies on identical twins, no longer secrete insulin. At this point, the daily insulin
concordance rates of only 30-40% have been reported for requirement plateaus at around 0.8-1 unit/kg/day.
type 1 diabetes suggesting that factors other than heredity
play an important role in the pathogenesis of the disease. Ambulatory Care
The most important genetic focus for type 1 diabetes Day-to-day management of type 1 diabetes involves
lies in chromosome 6 and is linked with expression of HLA medical management of glycemic control, and avoicl:lnce
antigens. HLA-DR3 and DR4 have emerged as important of acute complications and prevention of chronic
determinants of developing type 1 diabetes. Other genes complications on one hand and achieving social, scholastic
implicated in pathogenesis include insulin gene and and psychological goals of the child on the ot her.
cytotoxic T lymphocyte antigen 4 (CTLA4). Together these Comprehensive education and ongoing involvement with
genes can explain around 60% heritability of type 1 the family is mandatory. Teamwork approach ·..vith
diabetes. Protection against the disease is provided by the pediatrician/ endocrinologists, diabetic nurse educn tor,
HLA-DR2 haplotype. social worker and nutritionist is essential.
Infections predisposing to type 1 diabetes include
mumps, coxsackievirus, cytomegalovirus and rubella Insulin
(congenital rubella syndrome). Rodenticides have been Insulin is the cornerstone of type 1 diabetes management.
implicated in the development of diabetic ketoacidosis in The body secretes insulin at a basal rate with intermittent
Korea. There is increasing evidence that early introduction secretion with meals. The aim of management is to mimic
of cow's milk protein may be an important factor in the this pattern as best as possible.
subsequent development of diabetes in genetically
susceptible infants. This has led to delayed introduction Dose: Insulin dose is guided by pubertal status with lower
of cow's milk in infants. dose for prepubertal children (0.6 unit/kg/ day) compared
to pubertal (1.0-1.2 unit/kg/ day) and post-pubertal
There is substantial evidence for autoimmunity in type
children (1.0 unit/kg/ day). In the post-ketoacidosis phase,
1 diabetes. Lymphocytic infiltration around the beta cells
the dose may be as high as 2-2.5 unit/kg/day.
is found on autopsy of individuals of type 1 diabetes who
die due to incidental causes. At diagnosis, 70-SO% of white Preparations: Chemical modifications of insulin alter th~ir
children with type 1 diabetes have islet cell antibodies action profile providing flexibility in tailor made insulin
Endocrine and Metabolic Disorders 1543 -
r~--.---------- ._
I
· Table -19:40; Pharmac0kinetic profile of insulin preparations
preparation Onset Peak Duratfon Indications
Rapid-acting
Uspro 5-10 min 1-3 hours 3-4 hours Small child on mixed split regimen, insulin pump,
As part 5-10 min 1-3 hours 3-5 hours Multiple daily injections (MDI)
·Short-acting
Regular 30-SO min 2-4 hours 5-8 hours Diabetic ketoacidosis (OKA), mixed split regimen
Intermediate-acting
NPH 1-2 hours 2-8 hours 16-24 hours Mixed split regimen, basal bolus regimen
Long-acting
Glargine 2-4 hours Peakless 20-24 hours Basal insulin
Detemir 1-2 hours 6-12 hours 20-24 hours Basal insulin, mixed split regimen
Degludec 0.5-1 hours Peakless >24 hours Basal insulin
regimen. Currently all available forms of insulin are multiple daily injections is preferred in most children with
derived by recombinant DNA technology (Table 18.40). the exception in a resource-poor setting where a
conventional regimen is more practical.
Slwrt-acting (regular) insulin: Regular insulin that is
structurally the same as natural insulin, is the agent of Basal bolus regimen: Basal bolus regimen mimics
choice for IV infusion while managing diabetic physiological insulin secretion with the use of a long-acting
ketoacidosis (DKA). On subcutaneous administration, the basal insulin (detemir or glargine, 40-50% of total daily
medication forms hexamers in the skin, delaying onset of dose) and mealtime rapid-acting analog (aspart, glulisine
action by 30-60 minutes. Regular insulin should hence be or lispro, 50-60% of total daily dose, Fig. 18.30). The
given 30 minutes before a meal, which may be a problem mealtime dose is distributed over 3-5 times a d a y
in young children and toddlers with unpredictable eating depending on the diet pattern of the child. This regimen
patterns. The longer duration of action is helpful, if there offers flexibility, as changes in mealtimes do not cause
is a substantial gap between meals especially in school- significant fluctuations in glycemic control. The risk of
going children who have early breakfast and late lunch. hypoglycemia is also lower compared to mixed split
regimen.
Rapid-acting fosulins (lispro, aspart and glulisfoe): These
insulins do not form hexamers after injection and have Mixed split regimen (tw o or three injections p er d ay,
immediate onset of action. They are ideal for toddlers with Fig. 18.31): This involves the combination of short- and
irregular eating patterns and can be given even after a intermediate-acting insulin mixed at the time of injection.
meal. They provide better post-meal glycemic control The injections are given before breakfast (two-thirds of
compared to regular insulin and reduce the risk of daily dose) and before dinner (one-third of daily dose).
hypoglycemia. Insulin analogs are, however, expensive The ratio of short· to intermediate-acting insulin is 1 to 2.
and provide inadequate lunchtime cover on a two- This regimen has the advantage of less frequent injections
injection regime.
Intennediate-acting insulin (NPH): NPH is a chemically
.1. Short-acting
modified insulin (protamine) with prolonged duration of
action of 12-18 hours. It is traditionally used with short-
acting insulin for mixed split regime, but has significant
intra-individual variability in absorption resulting in Long-acting
fluctuating glycemic control. .1.
Long-acting insulin (glargine, detemir and deglitdec):
These long-acting forms provide peakless cover for Breakfast Lunch Dinner Bedtime
18-36 hours. They are useful as basal insulin in basal bolus
regimen. i i it
Fig. 18.30: Basal bolus regimen. Intermediate- (NPH) or long-
Insulin Regimen
acting insulin (glarglne or detemir) is given before dinner or at
The decision about the choice of insulin regimen is bedtime (40-50% of total daily dose; black arrow). Rapid- or
dependent on age, socioeconomic status an~ level .of short-acting Insulin (aspart or llspro) is given before each meal
glucose control of a child. A physiological regunen with (50-60% of total dally dose; blue arrows)
-544 I Eaaantlol Podlotrlce
I
Dlobolos Educallon
J. Short-acting
Structured dlnbctcs cducntlon i ~ mandiltory for the
mnnagcmcnt of dlnhctcs In children. K1:y an•.1q 10 ht·
covered In the progrnm Include pnt hophy.ri iolngy of
dlabt•lcfl, Insulin use, sick d.1y rnan11gcmcnl, hyp11;;lyccm1,1
nutrition, phys ic'11 nctlvlly and ~octa l issues (Table 18..Jt):
Nutrlllonol Managomont
Breakfast Lunch Dinner Bedtime The key lo s uccessful nutrltion;il rmmilgcm ('nt in type· I
tt tt Jiabctcs is flexibility. Ovcrzcillou.<t control i~ <l'><>oci.1lcd
with rl'bl'iiious behavior a nd d ietary indi'lcn ·lion. Thnc
Fig. 18.31: Mixed spilt regimen. Insulin Is given before breakfast is no 'diabetic diet' for children nnd they s hould bt
(two-thirds of daily dose) and dinner (one-third of dally dose). encouraged to hnvc a normal hea lthy di<'I. l mp,1rt.mc~
Each Injection Is a combination of Intermediate- or long-acting should be given to consistency of mca ltimings. D1t·t.1ry
(NPH or detemir; two-thirds of the total dose; black arrows) and exchanges and a 'nutritional pyr11mid 11pproach' arc u<;eful
short- (regular) or rapid-acting Insulin (llspro or aspart. one-third
in providing variety for children. Occasion nl trc,1ts during
of the total dose; blue arrows). Regular meal pattern Is required
to prevent hypoglycemia special occasions and eating out arc allowed, if COVl'T<'d
appropriately with insulin (Table 18A2).
Monitoring
J. Short-acting
Self-mo11itori11g of blood glucose (SMBG): SMBG is critical
for management of type 1 diabetes. It s hould ideally b~
done before each meal and at bedtime. Pos t-meal and
midnight blood sugars are measured as required, ad ju.;ted
according to the patient age (Table 18.-B). In children with
significant glycemic variability, continuous gluco'le
Breakfast Dinner Bedtime monitoring system (CGMS) provides information .1b•>uf
it tt glycemic control every 5 minutes over a 72-hour P'!riod
to help decide about insulin adjustment.
Fig. 18.32: Modified mixed spilt regimen. The night-time Hemoglobit1 A1c: HbAlc is a marker of glycemic Clmtrul
intermediate-acting Insulin has been shifted from before dinner over previous 3 months and is the best predictor o~ long-
to bedtime. This Is indicated In the presence of nocturnal term complications. Target levels for HbA le ure lb.; th.m
hypoglycemia and high pre-breakfast blood glucose levels. 7.5% in children and adolescents. These level · nuv b~
Delayed peak of intermediate-acting Insulin reduces the risk of falsely low in children with sickle cell dise.b . :> ..iron
nocturnal hypoglycemia on one hand while providing deficiency and increased red cell turnover as in ht·r~t•lvtic
reasonable cover for morning hyperglycemia
anemia. Falsely elevated HbA le levels are -:-c\:'n ..~i th
uremia and high dose aspirin treatment.
and lower cost. The regimen requires rigid dietary control
and strict lifestyle with regular mealtimes and snacks. In Follow-Up
a variation of the regimen, the interrnecilate-acting insulin
is shifted to bedtime to prevent nocturnal hypoglycemia Children with diabetes should be follow ed en.·n· th!1.~
and morning hyperglycemia (Fig. 18.32). months or more frequently as needed . Clinic.11J.!'!-L"' -nwnt
should include assessm ent of growth, pubcrt\ . Htii..iJ
Co11tin11011s subcutaneous insulin infusion (ins11/i11 pump): glucose levels, and examination of injection sik · ,ind 1.·.1n·
Insulin pump is an external device that infuses insulin at of feet. Children with pcrsis tl'nt hypoglyccm i.1 ~lhiul J be
a predetermined rate with additional boluses given at evaluated for adrenal insufficiency, hypot hrr-.Hdbn1,
mealtime. The basal dose can be adjusted for different celiac disense and diabetic ncphrop;1thy with dl· · n.>.b~d
times of the d ay and boluses tailored to different amount insulin excretion. Puberty is assod,ltl'd with ,111 inr:tl'.1St!
and types of meals to provide good glycemic control with in insulin requi rt•nwnt due to the dfl'ct of Sl'X h1m11one~
limited glycemic variability. Insulin pump is superior to and GH. The requirement furthl'r increases in i1dok:-0n'nts
basal bolus regimen in terms of insulin require ment, with obesity.
glycemic variabHity and weight gain. Closed loop systems
and insulin pumps with capability to detect blood s ugar Sick Doy Core
levels and infusing desired amount of insulin, arc expected Key aspects of sick dlly management include frrqlu:n;
to be available soon and provide physiological glyccmic blood g lucose mo nitoring, r egular fluid intake art
control. treatment of the .mtcrcurrent 1'11 nesses. Insu1·m rcqwr
. emrnt
- Endocrine and Metabolic Disorders
\ 545 -
Ill
Table 18.41: Diabetic education
Category Should know May know Optional
Disease Diabetes Is a lifelong disease Role of Insulin as Ille-saving therapy Glucose homeostasis
Normal outcome ls possible with Differences of type 1 vs. 2 diabetes Disease classification
appropriate therapy Pathophyslology of diabetes Role of autolmmunlly
Complications Disease associations
Treatment Insurin ·is th e only mode of treatment Insulin preparations Insulin regimens
Daily injections are a must Time course of Injections Insulin pumps
Physical activities Injection devices Newer Insulins
No alternative medicine Exercise and sports Competitive sports
Hope for the future
Skills Insulin storage Glycemic targets Ketone monitoring
Drawing up and mixing of insulin Insulin changes Glucagon Injection
Insulin injection techniques Ketone monitoring
S~lf blood glucose testing
Diabetes diary and log
· Nutrition Healthy eating RDA for age Carbohydrate counting
Avoid simple sugars Food exchanges Insulin to carb ratio
Mid-meal snacks High fiber intake Glycemic index
Follow-up Honeymoon phase Role of HbA1c CBGM
Hypoglycemia Complication Transplantation
Sick day guidelines Physical activity Career counseling
OKA prevention
CBGM: Continuous blood glucose monitoring; OKA: Diabetic ketoacidosis; RDA: Recommended dietary allowances
-··-·
i .. ·.·, .
·-· - Table 18.42: Nutritional guidelines for t}tpe1 diabetes
Component Recommendation Implication
'~= °'
Less tmn so msfdl..
0n;t CCfTE'C5:n of 1 I Encou.-age f..cifs,
- - ...
--: . -., .· _.,_ ..... -
~
Table 18.46: Complications of OKA Growth failure occurs in children whose diabetes is not
Acute well controlled. Mauriac syndrome occurs with poor
Chronic
control of diabetes and is characterized by hepatomegaly,
·Cerebral edema Growth hormone deficiency pale skin and extreme short stature.
Infections: Bacterial, fungal Mental retardation
Hypoglycemia Diabetes insipidus Delayed puberty is associated with inadequate control of
Hypokalemia diabetes and delayed bone age.
Acute respiratory distress
syndrome Hypoglycem ic unawareness is caused by frequent
Venous thrombosis hypoglycemia associated with tight metabolic control of
diabetes. It is due to impaired counter-regulatory response
cerebral edema should b e immediately treated with to hypoglycemia. Raising blood sugar targets and
intravenous mannitol (5 mL/kg) followed by fluid prevention of hypoglycemia usually causes reversal of
restriction and head end elevation. hypoglycemic unawareness.
Infections: Bacterial and fungal infections are common. Retinopathy is characterized by microaneurysms and
Indicators include persistent fever, leukocytosis, black proliferative disease. Earlier 80-90% individuals developed
nasal discharge (rhinocerebral mucormycosis) and eye disease b y 15 years of diabetes. With intensive
hemoptysis (pulmonary aspergillosis). management of diabetes this complication is delayed to
beyond childhood. Ophthalmologic examination should
Hyperosmofar Non-Ketotfc State
be conducted once the child is more than IO-year-old and
This condition is characterized by severe hyperglycemia has had diabetes for 3-5 years. Annual follow-up is
(usually >600 mg/ dL), hyperosmolality (>350 mOsm/kg), suggested.
low plasma ketones (negative or positive at <1:2 dilution)
and severe dehydration. Although chiefl~ a compl~cati~n Peripheral neuropathy is unusual in children and
of type 2 mellitus, it can occur in type I diabetes if msuhn adolescents. This results in decreased nerve conduction
is present to prevent ketoacidosis, but is insufficient to velocity and sensory changes. An abnormality in vibration
control the blood sugar. Management is similar to DK.A perception may be the first finding.
with a need for slower dehydration correction, more fluids
and lower insulin requirement. Nephropat11y is defined by presence of albumin in the
urine. Annual screening for microalbuminuria is initiated
Long-term Complications of Type 1 Diabetes once the child is 10 years of age or has had diabetes for
R~gular screening for long-term complications is esse~tial 5 years. If screening shows elevated ratio of spot urine
for their early identification, prevention a~d ~ppropnate microalbumin to creatinine, 24 hours urine microalbumin
treatment (Table 18.47). Screening for complications ~hould is estimated. Patients with significant microalbuminuria
be started after 5 years of diagnosis if the o~set of diabetes should receive ACE inhibitors to delay the progression of
is before puberty, and 2 years if diagnosed m puberty. nephropathy.
Lipoatrophy is fat atroph y at the inje~tion site. This can Dyslipidemia: Fasting lipid profile is performed on all
be prevented by rota tion of injection sites. children more than 2-year-old at time of diagnosis (after
Limited joint mobility, due to fl exion contractu~e.s of glucose control is achieved), or if there is family history
~etacarpophalangeal and proximal interphalangeal JOmts, of high cholesterol (>240 mg/ dL) and/ or a cardiovascular
lS typically noted in the hands. event before 55 years. If there are no concerns of hyper-
-sso 1 Essential Pediatrics
Table 18.47: screening for complications In chlldntn with type 1.cll'a6atea-mollllua -- ----· ---
Complications Indications Procedures Managemtmt
Retinopathy First eye examination after Initial examination of dilated lmprovomont In dlal>otoa 0011trol
3 months of diagnosis; fundus La9or troatmorit for vl~Ul\l looo
screening after 11 years
Prepubertal Duration of diabetes >5 years
from onset
Pubertal Duration of diabetes >2 years
from diagnosis
Nephropathy Annual screening after 11 years Annual screening for micro lmprovomont In dlabotoo control
Prepubertal Duration of diabetes >5 years albuminuria: Albumin excretion Control ol blood proosuro
from onset rate (AER) 20-200 µg/mln or ACE Inhibitors to roduco protolnurlo
Pubertal Duration of diabetes >2 years AER 30-300 mg/day
from diagnosis
Hypothyroidism At diagnosis; thereafter every Serum TSH and FT4 estimation Thyroxine therapy
2 years Thyroid autoantibodles
Hyperlipidemia Annual screening after 12 years Serum lipid profile Strict diet control
Prepubertal At diagnosis; thereafter every 5 years Stalins
Pubertal At diagnosis; thereafter every 2 years
lipidemia in the family, screening is performed after onset Type 2 Diabetes Mellltus
of puberty (>12 years). For pubertal children (>12-year- Type 2 diabetes in children nnd adolescents is incrc.1sing
old), a fasting lipid profile is performed at diagnosis after rapidly with the advent of childhood obesity epidemic.
glucose control is achieved. If LDL is <100 mg/ dL, lipid The disorder presents with milder symptoms than type l
profile is repeated every 5 years. If lipids are abnormal, diabetes though OKA can develop occnsionnlly. Di.1gnosis
annual monitoring is recommended in both age groups. is established based on presence of obesity, nc;rnthosis
Intervention is needed if fasting LDL >100 mg/ dL, initially nigricans, elevated insulin levels, normal C-pL'plid1•, .md
by dietary modification with decrease in saturated fat in lack of glutamic acid decarboxylnsc (GAD) nntilindics.
diet. A pharmacologic agent is added for LDL >160 mg/ Lifestyle measures and metformin nrc the mn i n ~t.1y of
dL, and in patients at risk of cardiovascular disease and treatment. Adolescent type 2 diabetes, however, h.1~ ""
LDL values 130-159 mg/dL after initiation of dietary aggressive course compared to adult type 2 dinbclc·:, with
changes and lifestyle intervention. The goal of therapy is faster loss of cell function. Children who prcsl·nl with
LDL level <100 mg/ dL. ketosis are treated with insulin initially nnd trnnsitwncd
to oral hypoglycemic agents once endogenous 1~lurosc
Hope for Future secretion recovers. These children and adolesccn l:- ,,: 1nuld
Given the need for lifelong treatment in type 1 diabetes, be evaluated for hyperlipidemia, diabetic retinop.1t h 1· .md
it is only expected that most patients seek permanent nephropathy at diagnosis. It is recommended that dutJ rcn
cure from the malady. Unfortunately no such cure is at risk of type 2 diabetes be regularly screened for di.1bctcs.
available at the moment. The efforts at developing cure
for type 1 diabetes are directed towards reversing the Monogenlc Diabetes of Young (MODY)
autoimmune process or restoration of f3-cell mass. MODY represents a group of inherited cond i ttons
Immunosuppressive agents (steroids, cyclosporine A, characterized by impaired cell function. The di ·order
azathioprine, anti-thymocyte globulin and anti-CD3 presents with relatively mild, non-ketotic diabetes in ,1 lean
antibody) have resulted in only partial and transient individual with strong family history of diabetes affecting
response. These strategies are limited by the fact that over three generations. The condition responds to lifcstylc
95% of f3-cell mass is destroyed by the time of diagnosis measures and low doses of sulfonylurea.
of the disease. The other, more appealing approach for
cure for type 1 diabetes mellitus, involves restoration of Neonatal Diabetes Mellltus
f3-cell mass using pancreatic, islet cell or stem cell Onset of diabetes before three months of life suggests
transplantation. Pancreatic transplant is a major neonatal diabetes. It is a challenging condition requiring
endeavor requiring long-term immunosuppression and meticulous monitoring and treatment. The diseas~
is not recommended in adolescents with type 1 diabetes. represents transient cell dysfunction (transient nconatnt
Studies have failed to show long-term remission with diabetes) permanent insulin secretion defect (permanen
islet cell or stem cell transplantation. neonatal diabetes) or congenital insulin resistance
Endocrine and Metabolic Disorders j ss1 -
~-----~------~~~....!:!::.::=::.:.:.:.::...=.:.:...=~~~~==-~~~~~~~~
syndrome_. The ~ost common cause of permanent • American Diabetes Association position statement: Standards of
•
neonatal d!abet:s is activating KATP channel, the on-off medical care in diabetes 2016. Diabetes Care 2016, 51 :112
button for msuhn secretion. These disorders are amenable • Atkinson MA, Eisenbarth GS, Michel AW. Type 1 diabetes. Lancet
to treatment with sulfonylurea. 2014; 383: 69-82.
• Dunger DB, Sperling MA, Acerini CL, ct al. ESPE/LWPES
Suggested Reading consensus statement on diabetic ketoacidosis in children and
adolescents. Arch Dis Child 2004;89:188-203.
• Acerini C, Craig ME, de Beaufort C, et al. Introduction to ISPAD • International Society for Pediatric and Adolescent Diabetes. ISPAD
Clinical Practice Consensus Guidelines 2014 Compendium Clinical Practice Consensus Guidelines 2014. Pediatric Diabetes
Pediatric Diabetes 2014;15:1-3. · 2014;Supp 20:1-290.
• American Diabetes Association. Clinical practice guidelines 2014. • Melendez-Ramirez LY, Richards RJ, Cefalu WT. Complications of
Diabetes Care 2014;37:514-85. type 1 diabetes. Endocrinol Metab Clin North Am. 2010;39:625--40.
Chapter
19
Diseases of
Central Nervous System
Rashmi Kumar
Status Epilepticus
of 5-10%, microarray' which examines the ':"ho.le genome,
. lds d'1agnos1s
. in. up to 2 00;.0 patients w ith intellectual Any seizure persisting for more than 30 minutes or multiple
Yie •
seizures, irrespective of duration, wi th no regaining of
disability with or without dysmorphism. Next genera~on
sequencing is an emerging technique that allows detection consciousness in between, is termed status epilepti.cus. A
. . changes through the who1e genome. single convulsion usually lasts for less than 5 minutes.. There
of single nucleotide
is a growing opinion that if a convulsion lasts beyond that
Suggested Reading time it should be treated as status epilepticus. As a corollary,
· amination of the child and if any child is brought conntlsing to the emergency, he
• Menkes JH, Moser FG. Neurologic ex M nkes JH Samat HB should be treated as status. In m-er SO'!C. of ca...-es. status
infant. In Child Neurology, 7th edn. ~d~. ~hiladelphia · 2006,
Maria BL. Lippincott Williams W1lkms, ' ' epilepticus occurs as the patient's first seizure. Status
PP 1-29. epilepticus is caused by the same entities that cause i..'01.ated
II HM !1annt1nl Podlntrlc•
r .. .' Aout•t'•"'' I
pl'lor unpmvoked IH!izurcs. Febrile seizures affect 3-8%
L'illld n~n up to 7 yearn of ngc. About 25-40% haven positive
!
fol!illy hl 11 tory. 7cvcr. mny be cau se~. by .minor upper
M11lntt1l11~tlrwuy,1Jrn~ill11t1u, 11lruuliHl011 I rekplralory lrad mfectmn, gastroe.ntcr1t1s,. v1r~I exanthcm,
I
I
A1tn11111~1ar wcyu~11
. .. . - ba clcrlul ln(cctlon, mnlurln or 1mmunizahon. Febrile
Uloml u1nutrulyt1111: gluoo1111; Helzurcl-l rnm1l be differentiated from ncute symptomatic
1mlolu1111 11111y11oiilu111; Heli'.ure11 dtw lo lnlrncranial infection and those triggered
!Ivor oml kltlnny tu11<Jllon lt11tl11; by foV<!r Jn chlklrcn wHh underlying epilepsy.
hlootJ oourtl!j;
tmlloology (If lnulCltiltJd)
.. -,Ypos
IV lomi opmn (0,1 r11ull1u) Ill' 111ll11vnl11111 (0.1 111y/ky); A s imple febrile seizure is n generalized seizure (without
1111 to~ doer111, I) 1111r111ttrn 11p111l
Corrnat nmlt1hollc1 flh11urrnnllty (11.u. IV yluuu1H1, II llypoylyoor11lu) focnl fcature1:1) that lasls Jess than 15 minutes and occurs
only once within a 24 hours period of fever in a neuro-
. --"·. -~- , 11 Ir .11nlzurt1~:~111;11~10;, . logically normal child . About 15-20'1'0 cases are complex
ndm ll~llltor llCJqu11nt111lly fcbrl le Hcizu re, diagnosed in presence of any of the following:
:w
IV.plrnnyloln or follpl1011ylol11 I
mylko l11luulu11
(I) focal 1:1igm1 or Hyrnploms; (ii) duration >15 minutes; or
(iii) recurrent seizures within the same febrile illness.
I --·· -- - i
Rflpflnt, If 1101}titJCI, ot 1o rno/ky
. Recurrenl febrile sei zures may be noted in children with:
(i) nge <18 months; (ii) family history; (iii) multiple
r.1v oocu;;,~~lr>ro~to 20.:..io mu/k1''"ru.~1or~ I seizures; (iv) first seizure at low temperature (<40°().
I . IV-,; ,~,..;;.;; •• 1±~6 :"'"'-;;;~ ,:,"81011 I It wns suggested thnt a prolonged febrile seizure in infancy
cnn cause hippocampal injury and mesial temporal
· ----c;~~-1,;iucod typhon~borbllono
sclerosis, leading to temporal lobe epilepsy. Subsequent
studies demonstrnte that a hippocarnpus that has already
I (or lhloponlono and propofol) Infusion been dnmagcd either by a perinatal insult or genetic pre-
- 1- ~~?_~!ld~r_ \-
disposition mny cause prolonged febrile seizure in infancy.
Management
[- -1v kotRmlno ; nd- 0~1:1l1~plra"2:'1~ _ j .E
An acute episode of seizure is terminated by intravenous
i · · · ·in101uiici1i1arili>'Y----••-•••· --- 01oiary 111iira.Jiy ·· ·: lornzcpmn or midazolam. In case the patient presents in
i Voool norvo stlmulollon Epllopsy suroory : status, standnrd protocol for management of s tatus
-· --·----- -- ~ ~~ -----~-------~·- ·· ··· ~-"-·------ - - ' epilepticus is followed.
Fig. 19.1: Sequential drug 1herapy In 111e management of status
epllepllcus In first episode of febrile seizure, lumbar puncture is
indicated in clinicnlly suspected meningitis or if Hib/
seizures: The condition cnn cause mulliorgan dysfunction, pneumococcnl immunization status is not known.
neurodevclopmcntal sequclac, nnd, in 1()0,{, cnses, denth.
Prophylaxis
Figure 19.l summarizes the management of stntus
epileptic us. The term nfraclory st·nl 11s ('pilC'pl ic11s is used for In children with risk factors for recurrence or those with
seizures thnt persist despite the use of benzodiazepine nnd frequent recurrences (2:3 in 6 months or 2:4 in one year),
one nnticonvulsnnt in npproprintc doses. Seizures that do intermittent prophylaxis reduces recurrences by 80% . Oral
not respond despite 24 hours of nnesthesin nre termed super- benzodinzcpines (diazepam 0.6-0.8 mg/kg/day in
rcfractory. · 3 divided doses or clobazam 0.8-1 mg/kg/ day in 2 divid~
doses) should be started at the first sign of any febrile
Febrile Seizures illness and continued for first 3 days of febrile illness.
Febrile seizures refer to seizures nssodated with high-
grade fever (>38°C) occuring in neurologically healthy Acute Symptomatic Seizures
children between 6 months and 5 years of age, without A seizure occurring within a week of acute neurolog~cal
underlying intracranlal infection and without history of · ·
m1ury, · act'1ve inflarnmatton
such as stroke, trauma, anox1a,
Diseases of Central Nervous System
,,,--------~------~~~---=~:=.::::..::..:....==:..:..:.~~~:=_:::~~~~~~~~~~- lsss -
nnd infection, nnd within 24 hours of acute metabolic of the affected limb of up to 24 hours may result, and is
dcrilllgcmenls, requires evnluation with serum electrolytes,
lutnbnr pun.cturc and neuroimaging if indicated clinically.
Antiepllephc thernpy is initiated and discontinued after
3-6 months if awnke and sleep EEG records are normal.
known as Todd's palsy. Focal or partial seizures may spread
to involve the whole body (secondary generalization).
Complex partial seizures are associated with
automatisms or loss of consciousness. Complex partial
seizures arising from the temporal lobe are also called
II
I
EPILEPSY psychomotor epilepsy. Patients may have a 'deja vu'
Epilepsy is defined as occurrence of two unprovoked feeling, visual, olfactory or visceral aura and peculiar
sciz.ures ov~r a day apart beyond the neonatal period. posturing or automatisms which are usually repetitive.
Pntien~~ with one unprovoked seizure and a high There is no memory for the event.
probability of further seizures in the next decade, similar
to the rccurr~nce risk (over 60%) following two Etiology
unprovoked. seizures, are also termed having epilepsy. Epilepsy may have genetic, structural, metabolic and
The International League Against Epilepsy (ILAE) 2017 unknown etiology.
classification categorizes epilepsy using semiological
phenomena at onset, as follows. Differential Diagnosis
Various paroxysmal events mimic epilepsy. Entities seen
Generalized Onset Epilepsy
commonly in children are discussed.
Tonlc-clonlo Benign neonatal sleep myoclonus: A well infant presents
A tonic phase lasting at least 30 seconds and associated with bursts of myoclonic or clonic movements only during
with uprolling of eyeballs, frothing from mouth, tongue sleep in the first week of life. The movements abort as
bite, perioral cyanosis and/ or incontinence of stool and soon as the child awakens. The conditions lasts for a few
urine, is followed by clonic movement of all limbs. weeks to months. Only reassurance is required.
Myoolonlo Breath holding spells: 1his behavioral problem usually
affects boys between 6 months and 3 years of age. The
Sudden, jerky shock-like violent contractions involve axial sequence of events is typical. The child first has a long
and appendicular muscles. cry, usually after being denied some demand. Then the
child holds his breath and turns blue and limp. This may
Atonle be followed by tonic and a few clonic movements. Parents
Sudden loss of tone involving axial and appendicular must be reassured and advised about consistent parenting
muscles. practices. They should refrain from giving into the child's
demand or giving him undue attention just after the
Spasm episode. Iron deficiency should be treated.
Well-sustained, sudden inward and/or outward Syncope: This usually occurs in the upright position. Patient
movements of head, neck, trunk and extremities occur in may have been standing immobile for sometime or have
cluster or in isolation. suffered sudden fear or emotion. The fall to the ground is
usually not as sudden as in a convulsion. The patient is
Absence pale and pulse is slow. The attack is aborted by lying flat or
Brief periods of behavioral arrest, lasting 30-60 seconds, with legs elevated as this improves the cerebral blood flow.
occur without associated motor phenomenon.
Psyclwgenic seizures: These occur more commonly in
Tonic older girls. Jhe patient subconsciously tends to gain
something. There are bizarre body movements with eyes
Only tonic phase, as described in tonic-clonic seizure, tightly shut and pelvic thrusts. Very often the child does
occurring without the clonic component. it when there is an audience around.
Focal Onset Epilepsy
Epileptic Encephalopathles
These may be motor, sensory or autonomic. They account
for 6001 · m· childhood· They more often Conditions in which epileptiform abnormalities them-
10 o f ep1.1eps1es . have
· selves contribute to progressive cognitive decline form a
1
a structural cause. Important causes are atrophic esions,
scars, inflammatory granulomas, strokes and vascular part of one of two common syndromes.
insults, head trauma, abscess and neoplasms. In our counhi~ch, West Syndrome
.
neurocysticercus granu1omas are a common cause,. w.
. . d' like enhancing 1es1ons This is the most common epileptic encephalopathy in
c1ass1cally produce a ring or isc . . .
on n · · A imple focal or partial seizure is not infancy, and is characterized by the triad of epileptic
eurormagmg. s · t a 1 · spasms, hypsarrhythmic EEG and psychomotor
associated with loss of consciousness. A transien P ra ysis
n-iarda-tion at regres5~on. Etio!ogy is drrase. Aln:c:sit a.~y Principle$ of Drug Therapy
t;,'pe of brain ms.wt in ea:rlj• life can !ea<l to thls syndro-me. T.abh? 19.-! shows agffits u::::eJ fur ,-.ui"('US ~b.1~ tyf'l":\
/,., b-'JUt r;.,-c;-fu1.rds. oztient.s are svmpt.omatic and cnt~.mi :\IJ parents and car~gh·er: s~ouki l't:' :h.h~s"--J fut
a-;pt..ogenfr:; the ~.Jtrome is ~u.ally better in fre !.an:a- domiciliary m.lilagemimt ot s~izun..~. wht~h mdudt"S
c.a teg.oq. Ti'.e tteatment of choice is either ..\CTH o-: pumng the dilld in ~,-&-y p...~iti0n ~m,i ,l.Jmin~~rit~
curtkos.ten:nd.s; alternatiYely, -.-igabatrin may be u...::.ed. mrr.ma...;.al or buoc.al nudnol.un or 11..'T.ln.'f'\m.
PtCY6f>00-1S for r:eu.rod~elopment is variable cmd depends _-\EDs are sb.rtOO ili~r tw-o U."tproYuk~i "'Fi~. .,l~ ('.t
011 seizure romroJ a.-"\d tmderlying etiology.
c-cneralized tonic donic ~i.zure$.. How~n~r. it is indk•\h.\i
f.E::UO/..fr..h.1?J1 5-;rr.Jrc.fl'.e
~a: a single episode if the n~uNim,\~it~ '-'r EEG is
cllnormal or the child h.!S pre;e.""l.~i in st.itus t>filt'~'ti...."1.ts,.
This. is cme of the mas.t d.Hficult epilepsies to treat. Chsct Initial ther.lpy i.s mcno!her..?py, initi.tlly in lcw ...i<W th'!t
occurs. in late inf~ or earlv childhood. ~fixed seizures,
is gradualh- increa....'€<l to maximum ph.1nn,\....\.'l0gk.llh-
induding tonk, a~c, my~lonic, atypiral ahsen...'"e ami !
tole..-ated do,e. Poh-theratw is indic.1h.-<l if th~re .u~
ar generalised toruc-donic seizures, are cha:raru::..-istic;_
Etiol0'6J' i; di?erse. Jntel1ectu.ll regression im·ariably
multiple ~ tyres or f;ilure to n..~pon. .i t\' m~'no
tha....rapy. Rational combination s.h uld l~ u~'1; dru,~ ''ith
if....CUH. EEG sho-.1.-s ger.erafued slow spi_\:e anrl sharp waYe
the same mech.mism of action ..md sinl.il.rr .1dn?~ ~fit\.i
act1vity of 1.5-2.5 Hz. Drugs used include vaiproate,
famotrigine, benzodiazeplnes, topiram.?te, Je.-etireret:am profile should be aYoided.
and zonis.mide. Th_~peutic options in refrac+.ory c.a...<:es Up to one-third of epilepsies are drug refr.Kt\'ry er
medicall\- intractable. Refr.actory ~pilepsy is usu.\lly
include dietary ,,, ther;ml;r
-r.J and '-t'--r-J
..mJPnC:1,.r sun?err.
o ""
defined a5 failure of 2-3 appropria~y cho...;;;en :\Elli \\ith
lnvMfigatk>ns a minimum number of dL.;;;.ablins Socizures, or the b.:k l'i
A video EEG is indie.lted in all cases of unprovoked remission m·er a certain period of time. \",1ricus f.'!.'-il.1r:;
Sf..-izure. Vl'ru]e a normal EEG does not rule out seizure, it like quality of life. natural history of the disc.'!.~<.' .md
is uu..fuJ in diagnosing epilepsy syndromes and pseudo- available treatment options determine intr.1.:t.'!.bility.
seizures and in enabling decisions regarding antiepileptic Therapeutic options include diet.uy ther.lfy, Y,1b.1l n~r..-e
drug withdrawal Some salient EEG findings are summa- stimulation. immunotherapy and epilepsy suI'~ry.
rized in Table 193. Jn tropic.al countries, neuroimaging
(prcforably MRI brain with contrast) should be done in Suggested Reading
aJJ ~with unprO">'Ok.ed seizure as neurocysticerrosis • Fenichel G".\.L ParoX>S.mal d isorder:$. In: Clinkal I'<?...i:Jtri.:
.. and tuberruJomas are the most common causes of seizures. ~eu..-u!ogy. ;th edn. ~unde.-s, Philacclfhl.J.. ::013; FP ~-=--:.·~-t
b
-
Fig, 19.2: Neural tube defects. (a) Tuft of hair overlylng spina bifida occulto; (b) Dorsolumbar meningomyelocele; (c) Occipital
encephalocele
-558 j EHentlal Pediatric•
Fig. 19.3: Findings In tuberous sclerosis Include: (a) Subependymal nodule on non-contrast CT of brain; (bJ Cortical tubers on axial
FLAIR magnetic resonance Imaging; (c) Hypoplgmented ash leaf macule; and Id) Hyperplgmented maculopapular taclal rash
(odenoma sebaceum)
Of.seases of Central Nervous System lssg-
Suggostod Reading
• Uni.- H. KJm.tl D. Sh· .i~w•my l- Common n.-urocul.Jncou'
s\n,IN.tm.""' .f'rdl.llr Ann ::0 15; ·U : ~%-SQ.l .
• , :-::1n.t G . Ncuw1m.l~ln>: of rh.1lo mahl4C' 0\ en·if."w and
.1J,.i1~ 1'1..·di.ur R.Jdiol ~ 1 5: "~ Surrl J . >J~\J--42.
Encephalopathles
Acute disseminated encephalomyelitis
Postinfectious: Typhoid, shigolla. Reye syndrome
Hypoxic encephalopathy. heat hyperpyre.xia
Metabolic: Diabetic acidosis, uremic coma, hepatic coma,
neonatal hyperbllirublnemla. lactic acidosis, mitochondrial
disorders. Inborn errors of metabolism
Fluid and electrolyte disturbances.
Hypematremia. hyponatremla, alknlosis, acidosis
Toxic: Heavy metals (lead. mercury, arsenic), insecticides.
Cannabis indlca, carbon monoxide
Fig. 19.5: Bulbor conjunctiva! telongiectoslo in a child with ataxia Post-vaccination
1elongiectosio
-sso 1 Essential Pediatrics
polymorphonuclear cells. Protein is mildly increased and lasting 7-10 days. In severe cases, signs of raised
sugar is normal. Etiology is determined in only a small intracranial tension and hyperventilation are followed by
proportion. Viral detection by CSF polymerase chain shock and rapid death. Others recover gradually over
reaction (PCR) or specific antibodies are necessary but weeks to months, but majority of survivors have
have low diagnostic yield. prominent extrapyramidal sequelae.
Sick patients require careful monitoring in an intensive
care unit, targeting maintenance of vital functions and Diagnosis
ensuring asepsis, adequate nutrition, good nursing care CSF shows nil to moderate pleocytosis with elevated
and appropriate physiotherapy. Symptomatic management protein and normal sugar. MRI shows characteristic
includes administering antipyretics and anticonvulsants changes in bilateral thalami, basal ganglia and midbrain
and measures to reduce intracranial tension. (Fig. 19.6a). JE virus specific IgM can be detected by ELISA
in CSF and serum and has 95% sensitivity and specificity
Japanese Encephalitis (JE) when performed in CSF by 10 days of illness; earlier
JE virus is the leading cause of viral encephalitis in India samples m ay be negativ e. Viral isolation and detection
and worldwide, with the majority of cases occuring in by PCR in CSF or brain during early illness has low yield.
Asia. In India, most cases are reported from southern and
eastern states with outbreaks during and after monsoons. Management
Management is essentially supportive, as outlined above.
Etiology and Transmission
JE virus is a single stranded neurotropic RNA virus Prevention
belonging to family Flaviviridae. The chief vector across JE can be controlled by reducing contact with mosquitoes
Asia is Culex tritaenirrhynchus, a zoophilic mosquito that (using insecticide spray, larvicides, bed nets and
breeds in rice fields. The infection is zoonotic, with pigs repellants), vaccination of pigs and location of pigsties
and Ardeid birds as the chief hosts that harbor, amplify away from human dwelling, a nd, most usefully, by
and transmit the infection without developing illness, vaccinating susceptible humans. However, human
despite signifincat viremia. Man is an incidental dead-end vaccination does not interrupt the natural cycle of JE virus
host in whom the brief viremia deters further transmission. and does not provide herd immunity. JE vaccination is
now part of the National Immunization Program in
Cllnlcal Features endemic states (see Chapter 10).
JE tends to occur in epidemics and outbreaks, chiefly Mouse brain killed vaccine: This was the earliest vaccine
affecting children between 5 and 15 years of age or young to be manufactured against JE but is no longer in use.
adults. A prodrome of fever, headache, vomiting and Live-attenuated SA-14-14-2 strain vaccine: This is the only
diarrhea, lasting a few hours to days, is followed by an live-attenuated JE vaccine currently availab le. It is
acute encephalitic stage with persistent fever, seizures, produced by Chengdu Biologicals and is being used in
coma, focal deficits and signs of raised intracranial tension the public sector in China since 1998, Nepal (since 1999)
•
Fig. 19.6: Magnetic resonance imaging in acute encephalitis. (a) Axial FLAIR images showing bilateral thalamlc involvement In
Japanese B encephalitis; (b) Coronal T2-weighted Images showing right temporal involvement in herpes encephalitis; and (cl
~al FLAIR Images showing bilateral subcortlcal and periventricular patchy asymmetrical white matter signal changes In acute
disseminated encephalomyelitis
Diseases of Central Nervous System
I ss1 -
and India (since 2006). Studies conducted in Nepal kg every 8 hour for 14--21 days. Howe,.-er, despite early
reported efficacy of 99.3°.4, in the same year, 985% after therapy, less than 4{Yf.., patients survi\-e without disabilit;.-
one year and 96.2% after 5 years. An Indian study found and 5% may relapse.
vaccine efficacy to be 94.5% after 6 months. Dose is 05 ml
given subcutaneous.
JC51 Vaccine-Ixiaro: This is a new generation formalin
inactivated vaccine manufactured by Intercell (Austria)
and distributed by Novartis Vaccines. It is prepared
from the SA-14-14-2 strain grown in Yero cells. This is the
Acute Bacterial Meningitis
This is a relatively oommon and potentially fatal condition.
A high index of suspicion is essential to enable timely
diagnosis and treatment.
II
only JE vaccine to have received US Food and Drug Risk Factors ond PatritCgSr.e-31.s
Administration (FDA) approval for use in adults and
Infections are most common in the first 5 years of life. Risk
children beyond 2 months of age. This vaccine produced factors include bacterial colonization of nasopharynx,
with Austrian collaboration is available in India as JEEV
overcrowding, po\·erty and male sex_ Anatomic defects
(Biological E Ltd) . Schedule is 2 doses 28 days apart
such as fracture base of skull, pilonidal s inus and
followed by a booster after one year. Dose is 0.25 ml below immunodeficiencies predispose to meningitis. Bac-.eremia
3 years and 0.5 ml beyond.
is followed by lodging of bacteria in choroid plexus and
Indian Strain vaccine: Another Vero cell-derived purified the meninges. An intense inflammation leads to meningeal
inactivated JE vaccine is developed from an Indian strain exudates, ventriculitis, peri\·ascular inflammatory
of the virus (821564 XZ) isolated in Kolar, Kamataka, exudates, venous occlusion, infarction, necrosis and / or
during the early 1980s and characterised by the National raised intracranial pressure.
Institute of Virology, Pune. This vaccine was developed
through public-private partnership between the Indian Etiotog;
Council of Medical Research and Bharat Biotech Ltd. It The causative organisms vary with age. In the first 2
has received manufacturing and marketing approval from months of life, the most common pathogens include Gram
the Drug Controller General of India and is being negative bacteria, followed by S:aphylococcus aurms., group
marketed by the name, JENV AC. B streptococci and Listeria mo1wcytogenes. Between 2-24
Cllimeric vaccine: Another JE vaccine under development months, Hemophilus injluen=ne type b infections are most
is the live attenuated YFV-17D/ JEV vaccine (Acambis, common, followed by Streptococcus pne11mo11iae and
UK). The premembrane and envelop (prME) genes of an meningococcus. Beyond 2 years of age, pneumococcus and
attenuated human vaccine strain (SA-14-14-2) of JE virus meningococcus are the most common organisms, followed
are inserted between core and nonstructural genes of a by Hemophilus injluenZ11e type b.
yellow fever 17D infectious clone, resulting in a live
chimeric vaccine. Recruitment for phase 3 studies is Cffnlcat Features
ongoing in Thailand. Oinical features var}' with age. N ewborn and 'oung
infants present with lethargy, poor feeding, shrill cr...- and
Herpes Simplex Virus (HSV) Encephalitis seizures. Older infants present with fever, poor reedmO'
This is the leading cause of sporadic encephalitis and has irritability and photophobia. A tense bulging anteri;;
a severe fulminant presentation with high rates of fontanelle in a febrile infant suggests meningitis. Older
mortality and disabling sequelae. A non-specific prodrome children present with abrupt onset of high fe,·er, se\·ere
of headache, malaise, fever and vomiting is followed by wuelen~g hea~ache, anorexia, myalgia, photophobia
altered consciousness, focal or generalised seizures and and merungeal signs, and may develop convulsions and
focal neurologic deficits. Presence of focal signs is coma.
considered characteristic of HSV encephalitis. Presentations Meningeal signs are lacking till 2 years of age. Si2115 of
include movement disorders, stroke, behavioral raised intracranial pressure include hyperte;sion,
disturbances, hallucinations and memory loss. bradycardia, bulging fontanelle, third or sixth cranial
Examination of the CSF reveals pleocytosis, mild nerve palsy, posturing or breathing abnormalities.
protein elevation and occasionally, red blood cells. EEG Papilledema is unusual, especially in infants. A search
may show a characteristic picture of periodic lateralised should be made for septic foci elsewhere. Purpuric rash
epileptiform discharges. Neuroimaging shows suggests meningococcemia.
characteristic temporal lobe signal changes, with MRI
being more sensitive than CT (Fig 19.6b). PCR for HSVl Dftterentiot Diagnosis
in the CSF has 75% sensitivity and 100% specificity and is Viral and tuberculous meningoencephalitis are the chief
considered the gold standard for diagnosis. differential diagnoses. The latter is particularly
Management includes supportive care and specific considered when faced with partially treated bacterial
antiviral treatment with intravenous acyclovir at 20 mg/ meningitis.
Essential Pediatrics
I
tuberculous Meningitis
ht.'n\\;\t\\'\\\ ,md dt'-\th . C$F t''\•\m\n,\foln t't'H'als rnised
l"'·tt~Urt\ t\\tNd tlu\d.• m.uk,,Hy h\1..'t't'c\$t'\l ct'\l count (often This is the most severe form of tuberculosis. Predisposing
\n th1)\t~md~ F~·'' nm\~) \'\\idly "~'"'l'l't$\'d 1.'f polymorpho-
factors nre young nge, presence of a household contact,
nudNr 1.."\'U:', \nCt\:\;\St'l.l 1"1\.'tt'\n and low :'USl\f (less Ihm\ recent measles nnd protein energy malnutrition.
~~\' \'\l th~ C\'.nrom\t,mt blO\'d su~,u) .. Grc\l\\ stain and
' Pathophyslology
b.\.:'lt'fl•\\ cu\tun.' m.w cn,\blt:- d\a~no~i:' . H\,\\'l'VCr, PCR to
d~tt,~t b..\1..'.~ri,,l DN~\ is nw1't' :O:t'\\:-:.iti\''-'- Otht'r u:-:t:-ful tests Primary infection is followed by intermittent bacillemia
al'C l.-th..''\. -~glutin.;lt\1..'n h.':-:t. 1.' ~'untt'rcurrt'nt \rnmuno- and seeding of meninges, termed Rich's foci. During stress
dt'\:'tf\."'lpho.t'C~is J.nd bk•\'ld cultm't'.. ln \'t.'ry t'arly cases, CSF and lowered immunity, these foci rupture to cause
~''\.,\min,\thm m,\y l~' norm,\l fc,r 1..·cll rount. pwtdn and tuberculous meningitis, with characteristic thick exudates
~u~,\r but culturt' may be p\'\.."iti\'~.. ln casl.':' partially trcnted in the basal cisterns and endarteritis.
with 'mtihi\)t\cs, CSF n'll count is hn\'Cl" nnd hns a
l"T'c::"<iomin,mL"\' of lymphlxyh.':-: and culture is sterile . Clinical Features
lma.~ing in bacterial menin~itis m<w be normal or show The first or prodromal phase of the illness is characterized
int~\S:meninge.,1l cnh,\\\ct:'m~nt or it{tr\lcranial complica- by nonspecific irregular fever, anorexia, irritability and
tions $uch as subdural effusion (Fig 19..7a) or empyema, occasional vomiting and lasts 1-4 weeks. The second stage
Yentriculitis. brain abscess, hydrocephalus or infarcts. has neurological manifestations like seizures, focal deficits
Other romplications include syndrome of inappropriate
and meningeal signs. The third stage is one of coma and
:.-t"Cretion of antidiuretic hormone and sequelae of injury
sequelae. Hydrocephalus (communicating or obstructive),
such as deafness, epilepsy, intellectunl disability,
decerebrate poshuing, cranial nerve palsies, optic atrophy,
neurological deficits and hydrocephalus.
extra pyramidal signs and focal deficits are more common
Treatment in tuberculous than other CNS infections. Chief differential
Empirical intravenous therapy with third generation diagnosis are partially treated bacterial meningitis and
cephalosporin should be initiated without delay. viral meningoencephalitis.
Vancomycin is added if there is lack of clinical response
Diagnosis
by -lS-72 hours. Antibiotics are revised based on results
of investigations .. Therapy is usually adrninstered for Diagnosis is based on clinical features and investigations.
3 weeks in neonates and for 7-10 days in older children. CSP typically shows raised pressure, up to 500 cells per nun3
Dexamethasone, adrninstered intravenously at 0.15 mg/ with lymphocytic predominance, increased protein :tnd
kg/dose every 6 hours for two days, beginning with the low sugar (level about half the concomitant blood sl!gar
first dose of antibiotic is considered useful in preventing level). However, CSP may mimic bacterial meningitis or
hearing loss and short-term neurological sequelae. be normal in about 10-15% cases each.
Neuroimaging often shows hydrocephalus and basal
Prevention
exudates (Fig. 19.7b). The diagnosis is supported by
The risk of bacterial meningitis is reduced considerably prolonged history of symptoms, family history of
by mass vaccination against hemophilus, pneumococci and tuberculosis, positive Mantoux (tuberculin) test, chest
Fig. 19.. 7: Computed tomography In acute encephalitis. Contrast enhanced Images showing: (a) Bilateral subdural effusion In a
child with acute bacterial meningitis; (bl Communicating hydrocephalus with basal meningeal enhancement In a child with
tubercular meningitis; (c) Ring enhancing lesion with eccentric dot In left parietal lobe suggestive of neurocystlcercosls:
and (d) Non-contrast Image shows multiple calcified neurocystlcerl lesions, described as 'starry sky'
Diseases of Central Nervous System I s63 _,
radiographic evidence of tuberculosis and findings on CSF Clinlcol Features and Diagnosis
examination and neuroimaging. The diagnosis is Patients are usually older than 3 years and present \\ith
confirmed if CSF culture or PCR is positive for recent onset of focal or generalised epilepsy. Neuro-
Mycobacterium tuberculosis or acid-fast bacilli are present. imaging re,·eals one or multiple ring-enhancing lesions
Gene Xpert is a quick cartridge based test for M. tuber- with perifocal edema (Fig. 19.7c) with or without an
culosis genome and drug resistance to rifampicin. asymmetric scolex within the ring. Patients may
occasionally present with encephalitis and raised
Treatment intracranial pressure with or without seizures.
Antitubercular treatment includes two months of four Neuroimaging in these cases reYeals cerebral edem<l in a
drug (intensive) therapy and 10 months of two drug brain studded with cysts in various stages, including
(maintenance) therapy (Chapter 11). Intravenous is enhancing and nonenhancing cysticerci, termed a 'starry
dexamethasone is followed by oral administered for 8-12 sky' appearance (Fig. 19.7d).
weeks to prevent sequelae. Patients with obstructive The combination of clinical and radiological findings
hydrocephalus require CSF diversion by shunt or third is usually diagnostic. Radiological differential diagnoses
ventriculostomy. include tubercular and Toxoplasma granulomas. Serology
by enzyme linked immunoelectrotransfer blot assay hns
Prognosis high sensitivity (100%) and specificity (83-100%) for
multiple and extraparenchymal neurocysticercosis, but
Prognosis is related to patient age and stage of disease at
diagnosis. Early treatment (stage 1) results in complete has poor diagnostic utility for one to few cysticerci and
cure. While 80% of patients treated in stage 2 of disease calcified lesions.
survive, 50% show sequelae. Only 50% of patients treated
Management
in stage 3 survive and 80% show sequelae. Complications
include hydrocephalus, optic neuritis, infarction and Symptomatic treatment of seizures is essential. Anti-
spinal block due to arachnoiditis. Sequelae include focal epileptic therapy is continued for at least 6 months and
neurological deficits, epilepsy, intellectual disability, until the lesions disappear. Definitive antihelminthic
blindness and occasionally, endocrinopathies. therapy is recommended for up to 5 lesions. Albendazole
is the preferred agent and is administered at 15-20 mg/
Neurocystlcercosls kg/ day in two divided doses for a week. Cysticidal
therapy is contraindicated in ocular neurocysticercosis and
Parasitic infestation of the brain by the encysted larvae of cysticercal encephalitis since degenerating cysts may
pork tapeworm Taenia solium is a public health problem evoke intense inflammatory response. All patients should
in many developing regions including Southeast Asia, first receive oral prednisolone at 1-2 mg/kg/day for 5-7
Latin America and sub-Saharan Africa. The condition days, beginning prior 2-3 days to antihelminthic therapy.
affects 9% people across ages and 13% of children.
Neurocysticerci account for up to 35% patients presenting Acute Disseminated Encephalomyelitis
with seizures in rural regions, with active or degenerating
Immune-mediated cerebral inflammation may follow viral
neurocysticerci being more common than calcified
exanthem or vaccination. While measles is the most
granulomas. Humans acquire the infection by consuming
common cause, causative infections include rubella,
undercooked pork containing cysticerci or by eating food
mumps, varicella zoster, influenza A and B, Ricketfsia and
contaminated with feces containing tapeworm eggs. The
Mycoplasma pneumonia. Vaccines that may precipate the
eggs form larvae that cross into the bloodstream to seed syndrome are rabies, vaccinia, measles and yellow fever.
the brain. Patients present with altered consciousness, convulsions
and multifocal neurological signs affecting cerebellum,
Pathogenesis optic nerves, long tracts and spinal cord. Fever may be
Parenchymal or cerebral infection is more common than absent at onset. CSF may reveal mild pleocytosis. MRI
extraparenchymal neurocysticercosis, manifesting as shows characteristic scattered lesions in the white matter,
intraventricular, spinal or ocular cysts or arachnoiditis. at times affecting the deep grey matter and other areas
Cysts may be single or multiple, and usually form at the (Fig. 19.6c). Treatment options include pulse corticosteroids,
gray-white matter interface. Four stages are recognised, intravenous imrnunoglobulin and plasmapheresis.
namely the vescicular, colloidal, granular-nodular and
nodular-calcified lesions. The first two or active stages Autoimmune Encephalitis
carry low risk of seizures and do not enhance on Neurological syndromes presenting with neuropsychiatric
neuroimaging. Cysticerci usually cause seizures in the features, mutism, movement disorders, seizures and
degenerating or granular-nodular stage, and are detected cognitive decline may be caused by serum and/ or CSF
as enhancing lesions on MRI. antibodies against ion channels, receptors and associated
111111 564 I ~~~~~--------~~---E_s_s_e_nt_la~l~P~e~d=la~tr~lc~s:.-...---~--~------------------~
Table 19.6: Etiology of cerebral palsi •· · -
0
I
Congenital or intrauterine infections
However, 23-40% of patients present in childhood.
Maternal or obstetric complications
Treatment options include pulse methylpredisolone,
Teratogens
intravenous immunoglobulin, plasma exchanges and
intravenous rituximab. Perinatal
Birth asphyxia
Encephatopathles Prematurity; low birth weight
Birth trauma; intracranial hemorrhage
The term encephalopathy is used for diffuse cerebral
Hyperbilirubinemia; hypoglycemia
dysfunction due to a non-inflammatory pathology, as
Central nervous system (CNS) infection
~gainst e.ncephalitis which is characterized by
mflammahon. However, the two are often difficult to Postnatal
distinguish clinically. Fever cannot discriminate between CNS infection
the two ei:iti~es a~ encephalopathy may be precipitated Hypoxia
by systemic infection, and fever may have an alternative Trauma; toxins
cause.
Dengue Encephalopathy affecting 2-3 infants per 1000 live births. While perinatal
asphyxia was considered the most common cause, it
Neurological manifestations, including encephalopathy,
accounts for less than 10% of cases. Various causes are
are common with dengue infections and may be caused
by vasculitis, cerebral edema, hypoperfusion or listed in Table 19.6.
hyponatremia. However, virus invasion of the brain Cllnlcal Features
producing encephalitis has also been documented.
The most common presentation is with developmental
Reye Syndrome delay. Physical findings are persistence of neonatal
This acute encephalopathy may follow a viral upper reflexes, increased tone, fisting with cor tical thumb,
respiratory tract infection (90% cases) or varicella (5-7%). scissoring of legs, toe-walking, abnormal posture and gait,
History of salicylate ingestion is common. The onset is abnormal movements and/ or hyperreflexia. Common
abrupt with protracted vomiting followed by delirium, co~orbidities inc~ude intellectual disability, microcephaly,
combative behavior and stupor. While most children have seizures, behav10ral problems, difficulty in speech,
a mild course, there may be rapid worsening with seizures, language, swallowing or feeding, blindness, deafness,
coma and death. Common findings include mild squint, malnutrition, sleep disturbances and exct-:..sive
hepatomegaly, hypoglycemia and elevated serum drooling. Contractures may develop that are initially
dynamic and later fixed .
transaminases (>3-fold) and ammonia and coagulopathy
with normal levels of serum bilirubin. Liver biopsy reveals Classification
diffuse microvesicular fatty infiltration without any
inflammation or necrosis. Cereb.ral palsy ~s cl.as sified topographic ally as
quad.nple?1c, hem1pleg1c, monoplegic or diplegic, and
Suggested Reading phys1.olog1cally as spastic, dyskinetic, ataxic or mixed.
• Kumar R, Tripathi P. Japanese encephalitis. In: PG Textbook for Spa.she pal~y ~ay be quadriplegic, diplegic or hemiplegic,
Postgraduates. eds: Gupta P, Menon PSN, Ramji S, Lodha R. Jaypee while dyskmehc palsy may be choreoathetoid or dystonic.
Brothers Medical Publications, New Delhi. 2015. pp 2144-2150.
Spast~c qua~ripl~gia is the most common type of cerebral
• Lehman RK, Schor NF. CNS Infections. In: Nelson Textbook of palsy m I~dia. It is often caused by perinatal asphyxia or
Pediatrics.eds: Kleigman RM, Stanton BF, St Geme JW, Behrman
RE 19th edn. Elsevier Philadelphia, 2011, pp 1998. neonatal illness. Common comorbidities are intellectual
• Kumar R. Viral encephalitis and encephalopathies. In: Medical disability, seizures, pseudobulba r palsy, microcephaly,
Emergencies in Children. Eds: Meharban Singh. 5th edn. Sagar squint or visual disturbances, speech abnormalities and
Publications. New Deihl. 2012; pp 324-32. deformities. Neuroimaging may show cystic encephalo·
malacia.
CEREBRAL PALSY Spastic diplegia is the second most common type, and is
Cerebral palsy refers to permanent, nonprogressive and linked to prematurity. Intellect is often p reserved.
occasionally evolving, disorders of tone, movement or Neuroimaging shows periventricular leucomalada.
posture, caused by an insult to the developing brain. It is Spastic 1iemiplegic palsy usually results from a vascular
the most common chronic motor disability in childhood, insult or perinatal stroke. Early hand preference is a clue.
Diseases of Central Nervous System
I sss -
Neuroimaging usually reveals focal changes or a deficiency. Static disorders such as cerebral palsy may
porencephalic cyst. These children are usually mobile. appear to regress due to formation of contractures,
They may have preserved or impaired intellect. epilepsy, movement disorders or emotional problems.
Dyskinetic or extrapyramidal palsy may result from Epileptic encephalopathies also cause neuroregression.
asphyxia or kemicterus. Rigidity, dystonia, dyskinesia and
drooling are prominent while intellect is relatively
preserved. Radiology may indicate abnormalities in basal
ganglia or thalamus.
Acute deterioration following illness, trauma or brain
infections after which the child remains static or improves
need to be differentiated. The neurocutaneous disorders
also have progressive neurologic deterioration. Diseases
like lupus erythematosis and multiple sclerosis can also
I
Ataxic palsy is caused by cerebellar malformations and appear like a progressive degeneration.
is associated with other cerebellar signs.
Mixed CP refers to a presentation including both spastic Evaluation
and extrapyramidal features. A detailed history should elicit the age at onset, course
and evolution of illness, history of consanguinity and
Evaluation
family history. Progressive deterioration may be difficult
A detailed history is taken to detect various manifestations to detect in patients with infantile onset. Other features
and antecedent events. Physical and neurologic include feeding difficulties, vomiting, failure to thrive,
examination should include detailed assessment of lethargy, irritability and lack of visual fixation and social
development and evaluation for dysmorphism and interaction. Small molecule disorders (aminoacidopathies;
neurocutaneous markers. Spasticity is classified using urea cycle disorders; organic acidemias and fatty acid
tools such as Gross Motor Function Classification System oxidation defects) typically have a relapsing and remitting
and Modified Ashworth Scale. course with progressive deterioration, while large
molecule storage diseases (lysosomal storage disorders;
Management glycogen storage disorders and mucopolysaccharidoses)
Management requires multidisciplinary inputs from the have chronic progressive course. Physical examination
pediatrician, occupational therapist, physiotherapist, should focus on appearance (Fig. 19.8), detailed
clinical psychologist, orthopedic surgeon, speech neurological examination including fundoscopy, hepato-
therapist, ophthalmologist, ENT specialist, social worker splenomegaly, and specific findings in eye, skin and
and special educator. Generalised spasticity is managed
by physiotherapy and drugs such as diazepam, baclofen,
tinazidine or dantrolene. Localized spasticity can be
effectively treated with injection of botulinum A toxin.
Some patients may require tendon release or tendon
lengthening. Dystonia is managed with trihexiphenidyl,
botulinum or levodopa.
Suggested Reading
• Evaluation of a child with cerebral palsy. Aneja S. Indian J Pediatr.
2004 Jul; 71(7):627-34.
• Fenichel GM. Hemiplegia, paraplegia and quadriplegia. In: Clinical
Pediatric Neurology. 7th edn. Saunders, Philadelphia. 2013.
Chapter 10, 11.p 236-70.
• Gulati S, Sondhi V. Cerebral palsy: An overview. Indian J Pediatr.
2017 Nov 20 [In Press].
• Stavsky M, Mor 0, Mastrolia SA, Greenbaum S, Than NG, Erez 0 .
Cerebral Palsy-Trends in Epidemiology and Recent Development
in Prenatal Mechanisms of Disease, Treatment, and Prevention.
Frontiers in Pediatrics. 2017; 5:21. doi:l0.3389/fped.2017.00021.
NEUROLOGICAL REGRESSION
Various disorders present with progressive deterioration
in mental and motor functions, causing loss of acquired
milestones. Inherited metabolic storage disorders are the
most common etiology; other causes include sequelae of
infections (e.g. HIV encephalopathy, subacute sclero~~g Fig. 19.8: Coarse facial features with psychomotor retardation
Panencephalitis and progressive rubella panez:tcep~alitis), In a chlld with (a) Mucopolysoccharldosls type 2: and
hydrocephalus, hypothyroidism and v1tamm B12 (b) Cretinism (congenital endemic hypothyroidism)
I
j
,_566
- - r - .. - - · - - - · - --~- -
Treatment
The first priority is to evaluate for and manage conditions
for which specific therapy is available, such as
hypothyroidism, hydrocephalus, vitamin B12 deficiency,
lead poisoning, Wilson disease, adrenoleukodystrophy,
and biotinidase deficiency. Specific diets are useful in
conditions such as galactosemia, fructose intolerance and
phenylketonuria. Enzyme replacement therapy is
available for Gaucher disease, milder variant of
mucopolysaccharidosis type 1, glycogen storage disease
Rg. 19.9: Characteristic predominantly posterior white matter
type 2 (Pompe disease) and Fabry disease. Transplantation
Involvement In a patient with adrenoleukodystrophy
of the bone marrow and liver may be useful in patients
skeJeton that may indicate the underlying etiology. with Hurler disease and glycogen storage disease,
Table 19.7 lists disorders based on age of onset; specific respectively. Several disorders are already screened .for
clinical and diagnostic features are discussed in as part of newborn screening programs in many count~e~·
Chapter 24. While most conditions have a poor outcome, specif•~
Biochemical tests are targeted towards detecting the diagnosis enables prenatal counseling and antenata
suspected defect and include serum ammonia, arterial diagnosis in subsequent pregnancies.
Diseases of Central Nervous System
I sa1 •
suggested Reading fright lasting a few minutes. Consciousness is maintained.
• Feni.che~ GM. Psychomotor retardation and regression. In: Clinical With time these attacks decrease and stop altogether and
Pediatric Neurology. 7th edn. Saunders, Philadelphia. 2009. typical migraine may develop.
pp. 113-146.
• Menkes JH, Moser FG. Neurologic examination of the child and Conversion Reaction
infant. In: Child Neurology. 7th edn. Eds: Menkes JH, Samat HB,
Maria BL. Lippincott, Williams and Wilkins Philadelphia. 2006. Hysterical ataxia is relatively common in older children
pp. 1-29. and adolescents. Although the hysteria is involuntary,
• Sheth J, Mistri M, Bhavsar R, et al. Lysosomal storage disorders in there is some secondary gain. The child does not have
Indian children with neuroregression attending a genetic center.
Indian Pediatrics 2015; 52:1029-33. difficulty sitting but when made to stand there is severe
swaying from the waist, so that she lurches and staggers
from one object to the other. Diagnosis is by observation
ATAXIA
only.
The term ataxia refers to disturbance of fine control of
posture and movement, usually caused by abnormalities Episodic Ataxias (EA)
of the cerebellum or its afferent and efferent connections, These are due to ion channel mutations. EA type 1 results
posterior column of the spinal cord or the vestibular from a mutation of potassium channel gene KCNA1 .
system. Ataxia may be acute and/ or recurrent or chronic Attacks of ataxia and myokymia of the face and limbs
and progressive (Tables 19.8 and 19.9). lasting 10 minutes to 6 hours in duration usually start after
5-7 years of age. EA type 2 is due to mutation in voltage
Acute or Recurrent Ataxia dependent calcium channel gene. Episodes of ataxia,
The most common causes in children are acute post- vertigo, jerk nystagmus with vomiting lasting one hour
infectious cerebellitis and drug toxicity, followed to a day occur 1-3 times per month. Onset is in school
by migraine, brainstem encephalitis and underlying age. Most patients are normal between attacks but some
neuroblastoma. Some of these are being described may have slowly progressive truncal ataxia and
below: nystagmus.
--- --,- ..
... ,_ ____ , ~- .. - •• ' ..... ,f~r-
Trihexiphenidyl, baclofen, carbamazepine, benzodia· ~eralize<l myodonus th'1t tl\.' tllrs chll:'f'I}' dmlt11{ nt lhm
zepines or levodopa may be useful. Outcomes vary from or stress, im-clhres the fol.'.e, tt·unk 1)1' t-H'U"l.lt11n l lll\11_1rll'!I,
complete disability to functional independence. has onset in first or St:.'(ond dc..:ndc of life, nl\d l1_111~!ltWl11lt1l1
with normal EEG and m~u1·oln1 A8 lng . Thc1·rtp}' with
Wilson Disease nitrazepam or donazepam tnA)' be usehtl.
Wilson disease, an autosomal recessive disorder
characterized by copper accumulation in liver, brain and Tics
cornea, presents variably at 3-50 years. Children usually These~ sudden, bl'id, pmposeles~. cumplto•;< sll1rtiutyptill
present with acute or chronic hepatitis or hepatic failure. mm·ements or utterances, which ore c\ ocl1 1'bntcll by 11ll'er.l~,
Neurological symptoms predominate in the second are suppressible and disappeal' dudn~ sll'cp. Exn111plr~
decade, and include disturbance of speech or gait, often include clearing the throo\t, c~°l' blinkinp,-. g1'11uod11g, llp
unchanged for years, followed by d ysarthria, dystonia, smacking and shrugging of shoulders.
rigidity, abnormalities of gait and posture, tremor and Tourctte symlromt is char,1ct\'rized by mnllir nf\d Vt•rbt1I
drooling. Dementia and psychiatric symptoms may also tics and attention deficit. Verbal tks lndudl• ~morlln g,
occur. Almost all cases with neurological involvement sniffing, grunting or hissing. Disl'asc l'llllt'se wn. l'N l\11d
show golden-brown pericorneal discoloration, termed wanes O\'er prolonged period. The cnmllthm I~ pcrlrnps
Kayser-Fleischer rings. Diagnosis is suggested by reduced caused by streptococcal inft'(tion in &t.•nctkully pt'l•dl~po~wd
serum ceruloplasmin levels ( <20 mg/ di), increased individuals. Pimozide, halopcridol or fluplwn11zil1e 11My
urinary copper excretion and increased hepatic copper
be used if the tics are bothe rsome.
content on biopsy. Patients require lifelong chelation with
oral D-penicillamine or trientine, titrated to maintain Tremor
urinary copper excretion at 5-10 times normal. Pyridoxine,
zinc and vitamin Eis given. Patients slowly recover over These are involuntary oscillating, rhythmic nml ll$t1.11ly
months. However, some patients progress to liver failure distal movements of low amplitude on both silks of :in
despite therapy, necessitating liver transplantation. axis. Tremors may be physiological, pn·cipia l11h•d by
anxiety, fatigue, stress or drugs s uch ns xn nthlrit·~ ,
Pantothenate Kinase associated Neurodegeneratlon adrenergic agonists, nicotine, th y rnid ho1·n10ne and
amphetamines. Tremors may be secondnry to injury to
Pantothenate kinase associated neurodegeneration is an
autosomal recessive disorder associated with iron deposi- basa l ganglia following meningoenccphnlilis .rnd
neurodegenerative diseases.
tion in basal ganglia. Patients present with progressive
dystonia, initially affecting feet, leading to equinovarus Infantile Tremor Syndrome
deformity, followed by rigidity in hands. Two-thirds
patients have retinitis pigmentosa while one-fourth Infantile tremor syndrome was described in l'. rlusi\·1·ly
develop seizures. MRI is characterized by 'eye of tiger' breastfed Indian infants, presenting at 8- 113 months of .1gc
appearance of the basal ganglia on TI-weighted images. w ith listlessness, developmental delay ;rnd rcg re:-:su1n,
Management is symptomatic. pallor, depigmented sparse hair and hy pcrpignw1ill'd
knuckles. Subsequent symptoms include prof; n•ssiVl' li 111h
Symptomatic Genera/zed Oyston/a tremors, bleating cry, and arms positioned likl' a 'bird
Symptomatic generalized dystonia may follow various about to take flight'. The condition is linked to cob;'1lamin
types of brain injury. Progressively severe dystonia is deficiency and responds to therapy with cobalnmin on<l
observed beginning 2- 3 years after kernicterus or perinatal propranolol.
asphyxia. Patients with stroke, head trauma, tumor of
basal ganglia, antiphospholipid syndrome and neuronal Suggested Reading
storage disease may show hemidystonia. • Fenichel GM. Movement disorders. In: Cllnicol P1•clintrlc
Neurology. 7th edn. Saunders, Philadelphln. 2013; pp 277-294.
Myoclonus • Kruer MC. Pediatric movement disorder~. Pcdirttr Rev 201 5; 36:
104-116.
These are sudden, brief, jerky, involuntary movements • Schlaggar BL, Mink JW. Movement disordNs in children. l'cdiutr
that are focal, multifocal or generalized. Generalized Review 2003; 24:39-50.
myoclonu s is not stereotyped. Myoclonus is more • Silveira-Moriyama L, Kovac: S, et nl. Phenotypes, genotypes, and
common when awake but may not disappear completely the management of paroxysmal movement disordNs. Dev. Med
Child Neurol. 2018 (In press).
during sleep. It may occur in isolation, as part of myoclonic
epilepsy, where EEG shows epileptiform discharges, or
STROKE
as part of systemic or CNS disorders. Myoclonus cannot
be voluntarily suppressed. A very wide variety of systemic Neurological w eakness of one-half of the body (upper and
and central nervous system disorders can cause lower limb), termed hemiplegia, is caused most commonly
myoclonus. Essential myoclonus refers to focal or by a stroke, defined as rapidly developing focal or global
Diseases of Central Nervous System j s11 -
disturbance of brain function lasting more than 24 hours most common (90%) presentation is with hemiparesis,
with no obvious nonvascular cause. Other causes of
hemiplegia include transient ischemic attack, Todd palsy,
granuloma, tumor, abscess, encephalitis, demyelinating
disorders, congenital brain malformation, neurocutaneous
disorders and migraine.
hemisensory signs, aphasia and/or visual field defects.
Cortical strokes may cause convulsions, contralateral
hemiparesis, cortical sensory loss and aphasia. Internal
capsule infarction may cause contralateral dense
hemiplegia, upper motor neuron type of facial palsy,
I I
Stroke may be broadly classified as ischemic or hemianesthesia and homonymous hemianopia. Altered
hemorrhagic variants that account for 55% and 45% of all sensorium may occur with posterior fossa stroke.
cases in childhood, respectively. Ischemic stroke may be Brainstem infarction causes crossed paralyses of cranial
caused by arterial thrombi or embolism or due to cerebral nerve ipsilaterally and contralateral limb palsy.
venous sinus thrombosis. Weakness due to stroke is Initial stabilisation includes attention to airway,
typically sudden, worst at the onset and improves breathing and circulation, supportive treatment for
gradually over days to months. Almost 20% of childhood hypoxemia, hypoglycemia, dehydration, seizures and fever.
stroke is recurrent. Thrombolysis with tissue plasminogen activator (tPA),
adminstered intravenously within 3 hours and intra-
Acute lschemlc Stroke arterial within 6 hours of the event, are recommended in
One or more risk factors for acute ischemic stroke, listed adults; however, no clear guidelines are available for
in Table 19.11, are present in two-thirds of patients. In the children. Pending investigations for cause, ultra-
others, no cause for stroke can be found despite extensive fractionated or low molecular weight heparin may be
evaluation. Patients with arterial thrombi may have administered.
prodromal symptoms, stuttering course and history of Suggested evaluation is listed in Table 19.12. Neuro-
transient ischemic attacks, while those with embolism irnaging should be done as soon as possible. Ultrasound
usually present with sudden loss of function. The precise is useful if fontanelle is open. Transcranial Doppler shows
neurological deficit depends on the site of infarction. The changes in cerebral blood flow velocity in moderate to
... ~ ~ - ~-- ---~
F"
••• •
'
... .... j - •
Table 19.11: Risk factors for acute ischemic stroke
. . ·-
Cardiac disease
Complex cyanotic heart disease Fibrillation; sick sinus syndrome; heart block
·' Infective endocarditis Valvular heart disease
Cardiomyopathy Prosthetic valves
Atrial myxoma; rhabdomyoma Patent foramen ovale
Hematological
Iron deficiency anemia Disseminated intravascular coagulation
Sickle cell disease Hemolytic uremic syndrome
Polycythemla Thrombotic thrombocytopenic purpura
Leukemias
Prothrombotlc disorders
Protein C or S deficiency . Prothrombin gene mutation G20210A
Antithrombin Ill deficiency Hyperhomocysteinemia
Activated protein C resistance Antiphospholipid antibody syndrome
Factor V Leiden mutation
Vascular conditions
Cervicocephalic arterial dissection Neurofibromatosis
Moyamoya disease Vasculitis: Primary; secondary to lupus
Fibromuscular dysplasia Infections: Tuberculosis; varicella
Diabetes
Metabollc conditions
· Homocystlnuria Organic acidemlas
Mitochondrial encephalomyopathy lactic acidosis and stroke Ornithine transcarboamylase deficiency
· Fabry disease Pyruvate dehydrogenase deficiency
I
Complete lipid profile Capillary telangiecia.Sis
Imaging: Carotid Doppler; computed tomography if hemorrhage Cavernous ma!fOf'fW....tio1ilS
suspected; MR Imaging, arteriography and venography; carotid Aneurysms
angiography, if indicated Bleeding and clotting dia!Besis
Echocardlography and electrocardiography Vascufrtis
Evaluation for procoagulant state Hypertension
• During acute phase: Serum homocysteine levels; genetic Trauma
testing for mutations (factor V Leiden, prothrombin gene);
activated protein C resistance; lupus anticoagulant,
antlcardiolipin and 1~2 glycoprotein-1 antibody lntracranlal Hemorrhage
• After 8-12 weeks: Levels of protein C, S and antithrombin Ill Clinlc.al presentation is more dramatic than ~·.im is&~
s troke, with severe headache and vomiting due~ :r-»sed
Antinuclear and antl-neutrophil cytoplasmic antibody;
rheumatoid factor intracranial pressure, and meningeal signs d u e ro leakrr..3
of blood into the CSF. Causes of intracranial r.emodreg~
are listed in Table 19.13. A thorough e , -a!uation i5
warranted as a potential cause is found in about 9[P.,,ca.-.o_
It must be noted that cerebral venous sinus ~-5
also can result in ICH because of back pressure.
er scan is preferred to .fv{R.I in diagnosis of h emmnaga
MR, er or 4-vessel carotid angiography is required to
delineate arteriovenous malfonll2ltions and aneu..r:-"""5:::;-.s..
Complete blood counts, including platelet count, clo::L-.g
factor assays like von Willebrand factor antigen, fac:;:ir
VIII and factor XU and liver function tests are require-::.
Management consists of resuscitation and suppor::-:-e
care. Identification of the cause may be follm,·ed by d.::E:-i-
tive treatment, in addition to rehabilitati.-e measures.
severe ischemia. CT is preferred in unstable patients or Table 19.14: Risk factors for cerebral venous sinus thromb'":.s
when intracranial hemorrhage is suspected. It may be Dehydration, hypoxia
normal in early ischemic stroke for up to 72 hours after
Cardiac disease: Congenital, postoperative, post-catheterizc.;.,°Jn
onset, after which there is edema in the affected area
(Fig. 19.10). MRI can identify ischemia within hours and Anemias: Sickle cell disease, iron deficiency ane mia,
thalassemia
diffusion weighted imaging within 45 minutes. While four
vessel carotid angiogram is most accurate for distal Head and neck infections
arteries, lesions of internal carotid artery, moyamoya Metabolic: Homocystinuria; prothrombotic disorders
disease, arteriovenous malformations and aneurysms, MR Nephrotic syndrome
angiography is a satisfactory alternative. Malignancy: Leukemia, lymphoma
Appropriate rehabilitation should be planned. Long- Systemic diseases: Systemic lupus erythematosus, Beh~et
term low dose aspirin is administered to prevent disease, inflammatory bowel disease
recurrence. Treatment of the underlying cause is important Drugs: L-asparaginase. oral contraceptives, steroids
to prevent recurrence. Conditions with a high risk of
Other structural conditions: Head injury. brain tumor.
recurrence (e.g. cardiac or prothrombotic disorders)
hydrocephalus, Sturge-Weber syndrome
require long-term oral anticoagulants.
Diseases of Central Nervous System ls13 -
empty delta sign. CT or MR venography is more definitive. ·· Table 1s.15: Causes of paraplegi8or quadrlplegla
Diffusion and perfusion MRI and digital subtraction Spastic
angiography are needed in equivocal cases. A detailed
evaluation for prothrombotic states is essential. Compressive
•
Tuberculosis of spine with or without paraspinal abscess
Initial treatment is supportive. Antibiotics are given if
bacterial infection is suspected. Ultrafractionated heparin Extradural: Metastasis from neuroblastoma, leukemia,
or low molecular weight heparin followed by warfarin lymphoma; inflammatory process, such as epidural abscess
(usually posterior to the spinal cord), bony abnormalities such
for 3-6 months is the treatment of choice. Thrombolytic as achondroplasia, Morquio disease, hemivertebrae and
treatment is recommended only in selected cases. occipitalization of atlas vertebra, atlantoaxial dislocation
lntradural: Neurofibroma, dermoid cyst
Suggested Reading
lntramedullary: Glioma, ependymoma, hemato· or hydro-
• AHA Scientific statement management of stroke in infants and myelia
children. Stroke 2008; 39: 2644-2691.
Noncompressive myelopathies
• Crawford LB, Golomb MR. Childhood stroke and vision: A review
of the lite rature. Pediatr Neurol. 2017; doi: 10.1016/ Vascular anomalies of the spinal cord: Arteriovenous
j.pediatrne urol.2017.11.007. malformations, hemangiomas and telengiectasia
• Rosa M, De Lucia S, Rinaldi VE, et al. Paediatric arterial ischemic Trauma or transaction of cord
stroke: acute management, recent advances and remaining issues. Transverse myelitis/myelopathy: Viral, neuromyelitis optica,
Ital J Pediatr 2015; 41:95-107.
segmental necrosis due to vascular occlusion, e.g. of anterior
• Tsze DS, Valente JH . Pediatric stroke: A review. Emergency
Medicine International 2011; 2011 :734506. spinal artery
Familial spastic paraplegia
PARAPLEGIA AND QUADRIPLEGIA Lathyrism
Degenerative spinal cord disease
Paraplegia refers to weakness of tnmk and both lower
limbs, while quadriplegia denotes weakness of all four Supra-cord lesions
limbs. Paraplegia or quadriplegia may occur due to Cerebral palsy
disorders of cerebrum, spinal cord, peripheral nerves, Hydrocephalus
neuromuscular junction or muscles (Table 19.15). While Bilateral cortical disease
cerebral disorders are upper motor neuron type, spinal Bilateral white matter disease
cord lesions may cause either upper or low er motor Flaccid weakness
neuron involvement and the other three types of lesions Spinal shock in the initial stages of spinal cord damage, e.g.
show lower motor neuron involvement. after trauma, vascular, inflammatory, neoplastic lesions, or
transverse myelopathy
Cerebral Disorders Guillain-Barre syndrome
Lesions involving parasaggital and periventricular areas, Acute poliomyelitis
Spinal muscular atrophies
in particular, cause paraplegia or quadriplegia. Common
Peripheral neuropathies
causes include perinatal asphyxia, structural malformations
Botulism, Riley-Day syndrome
and sequalae of CNS infections.
Pseudoparalysls
Spinal Cord Disorders Surgery, osteomyelitis, fractures, myositis, metabolic myopathy
These may cause acute or chronic progressive paraplegia
or quadriplegia. Cervical cord lesions present as in isolation or as part of Down syndrome, mucopoly-
quadriplegia, whereas lower lesions present as paraplegia. saccharidosis (e.g. Morquio syndrome) o r Klippel-Feil
Lower motor neuron signs are present at the level of the syndrome (decreased number and abnorma l fusion of
cord lesion and upper motor neuron signs are noted below cervical vertebrae). These are later replaced by upper
the lesion. Acute transverse lesions of the cord may cause motor neurone signs within a few days to weeks.
spinal shock with loss of all motor, sensory, autonomic
and reflex functions below the level of lesion. Patients with Transverse Myelitis
chronic spinal cord lesions present with clumsy gait, foot Transverse myelitis is an acute demyelinating condition
deformity and/ or stunted limb growth. Malformations of the cord characterized by sudden onset of often symme-
like meningocele and meningomyelocele are obvious at trical leg weakness ,..,.ith loss of reflexes, movements and
birth. The skin overlying spinal dysraphism may show sensation below a certain level with bladder and bowel
abnormalities like pigmentation, tuft of hair, lipoma or dysfunction over 1-2 days. Longitudinally extensive
sinus. Congenital atlanto-axial dislocation may cause acute transverse myelitis may occur with optic neuritis sequen-
or slowly progressive quadriplegia at any age, and is tially or together, termed Devic disease (neuromyelitis
usually caused by odontoid hypoplasia, occurring either optica). Diagnosis is enabled by contrast enhanced
--
- s14 I ~--------~~-------------=E!ss~e~n~t~la~l~P~e~d~la~t~rl~c~s:____--------------------------~----..
magnetic resonance imaging of the cord ..High dose ~HEA~D~AC~H~E~~~~~~~~~~~~~-
intravenous steroids are the treatment of choice. Headache is a common reason for neurological consul ta-
. · hildren Headaches may be acute, recurrent or
hon m c · . . d
Spinal Muscular Atrophy chronic and primary (e.g. migraine) or secon ary to an
Spinal muscular atroph~ is a heredit~ry disorder
Pathophyslology
The brain and most of the dura and ependyma are pain
insensitive. Pain sensitive intracranial structures are
muscles are spared and the baby appears alert. Type 2 vascular sinuses, large arteries and dura mater at the base
presents between 6 and 18 months of age and type 3 of the brain, and extracranial structur~s are skin,
presents after 18 months of age with motor delay. subcutaneous tissue, cranial nerves, arteries, muscles,
Diagnosis is by molecular testing. periosteum, sinuses and teeth. Inflammation, injury,
displacement or traction of these structures. may cause
Spinal Cord Compression headache. The trigeminal and upper cervical nerves
Spinal cord compression may be caused by congenital mediate the pain sensations.
lesions, tumors, Pott's spine, and disc prolapse. Root pains
may be an initial symptom. It is important to remember Evaluation of a Child with Headache
that early symptoms of a compressive cord lesion may be Evaluation is primarily clinical and investigations to
missed especially in a young child and they may present rule out serious underlying disorders are required
suddenly like an acute noncompressive cord lesion. infrequently. A detailed history about the pattern of
Polyneuropathy
headache should include description of episodes,
frequency, duration, location and associated symptoms.
The most common polyneuropathy presenting as quadri- Severe progressive recent onset headache may suggest
plegia is acute inflammatory demyelinating polyneuropathy intracranial pathology. Neurologic examination should
or Guillain-Barre syndrome. This postinfectious immune- include fundus examination.
mediated disorder presents acutely with symmetrical
ascending paralysis, early and complete loss of deep Migraine
tendon reflexes with or without sensory changes like pain,
paresthesias and loss of position and vibration sense. Migraine presents as acute recurrent headache occurring
Autonomic disturbances may occur. Involvement of in episodes lasting 2-72 hours. Migraine accounts for 75%
thoracic muscles may cause respiratory insufficiency, of consultations for headache, affecting about 10%
which is important to recognize. Treatment options children aged 5-15 years. Below the age of 7 years, both
include intravenous immunoglobulin and plasmapheresis. sexes are equally affected. At older age, girls are affected
more often. Typical features include unilateral localization
Neuromuscular Junction Disorders (in two-thirds of patients), throbbing character, moderate
Myasthenia gravis usually presents with ptosis and to severe intensity, triggering by stress, exercise, trauma
weakness of extraocular muscles worsening in the later and menstruation and association with nausea, vom iting,
part of the day. It may occasionally cause generalized photophobia and phonophobia.
weakness. Repetitive nerve stimulation test shows a .Mi!?raine ~s c~assified as migraine with aura (classic
decremental response. Antibodies against acetylcholine ~gra~e), rru?1°ame without aura (common migraine) and
receptors are found in up to 85% of generalized immune migraine equivalents. Migraine without aura is twice as
mediated myasthenia. common among school age children as migraine with
aura, but both may occur in the same person. Usual
Muscle Disorders features o! aura .are visual aberrations, flashing lights,
These cause proximal weakness, usually with preserved c~loured line~, bl.md spots, blurred vision, hemianopia or
deep tendon reflexes. . v1s':1al hallucinations. Dysesthesias of limbs and perioral
regi~n, focal mot?r deficits like hemiplegia, ophtha\mo-
Suggested Reading plegia and aphasia may also occur. Aura is transient and
usua~y last~ less than .a day. Migraine equivalents are
• Fenichel GM. Paraplegia and quadriplegia. In: Clinical Pediatric
Neurology. 7th edn. Saunders, Philadelphia. 2013; pp. 253-269. tra~s1tory disturbance m neurologic function, including
• McD.onald CM. Clinical approach to the diagnostic evaluation of beru.gn paroxysmal vertigo, cyclic vomiting, paroxysmal
herd1tary and acquired neuromuscular diseases. Phys Med Rehabil torhcollis, acute confusional migraine, hemiplegic
Clin N Am 2012; 23:495-563. migraine and ophthalmoplegic migraine.
• Menezes MP and North KN. Inherited neuromuscular disorders: Family history is present in 90% cases, especially in
Pathway to diagnosis. J Paediatr Child Health 2012; 48:458-465. classic migraine. Inheritance is believed to be multi-
j s1s •
fa:tori?l ra~her than Mendelian, and familial hemiplegic
~ Table 19.16: Causes of raised intracranlal pressure
m1grame is the only well-established monogeneic
migraine syndrome. Hydrocephalus (For details,see Table 19.19)
Known triggers. of migraine should be avoided. During Central nervous system fnfections
the attack, the child should be given an analgesic and lntracranlal hemorrhage
~sked to rest. Nonsteroidal anti-inflammatory drugs like Space occupying lesions: Tumors, granulomas, abscesses
ibupr~fen are usually effective. Sleep is also effective; the Metabolic causes: Reye syndrome; Inborn errors of
attack IS usually over by the time the child awakens. Selective metabolism, acute hepatic failure
sero~onin agonists. like sumatriptan, available as oral, Arterial, venous stroke
sublingua.l preparations and nasal sprays, are effective and
Hypertensive encephalopathy
non-sedative. ~vere migraine may benefit from intravenous
prochlorperazme maleate, dihydroergotamine or sodium Idiopathic
v.alp.r?ate. Prophylactic therapy is indicated, if there is
s1gruf1cant schoo~ absenteeism. Flunarizine, amitriptyline, Clinical Features
propranolol, top1ramate and valproate may be used. Symptoms of raised intracranial pressure are headache,
vomiting and visual disturbances, progressing to focal
Tension Type Headache
neurological deficits and coma. Chronically raised
This is a common type of headache, affecting 10-25% of intracranial pressure before closure of sutures results in
children, with a lifetime prevalence of 70%. Headache could increased head size and hydrocephalus, presenting as
be episodic or chronic, persisting for weeks or months. bilateral sunsetting, tense bulging anterior fontanelle,
Episodic tension type headache affects all ages and both hypertension and bradycardia. Sixth cranial nerve palsy
sexes and is related to fatigue and stress. The pain is a due to raised intracranial pressure, termed a false
constant ache usually localized to the back of head and neck. localizing sign, presents as squint and diplopia. In older
It is probably mediated by sustained contraction of muscles patients with closed sutures, percussion of the skull
attached to the skull. While nausea and vomiting are absent, produces a sound like a cracked pot, termed a positive
photophobia and phonophobia may occur. Macewen sign. Herniation of brain tissue causes various
clinical syndromes (Table 19.17), compression of the
Suggested Reading brainstem, coma and death.
• Fenichel GM. Headache In: Clinical Pediatric Neurology. A signs
and symptoms approach. 6th edn. Saunders, Philadelphia 2009; Management
pp. 76--89. Invasive methods to monitor intracranial pressure with
• Headache Classification Committee of the International Headache
Society (IHS) . The International Classification of Headache
intracranial catheters and transducers should be used onlv
Disorders, 3rd edn. Cephalalgia. 2013; 33:629-808. in intensive care setting with strict aseptic precautions and
are contraindicated in presence of coagulopathy. Measures
RAISED INTRACRANIAL PRESSURE, SPACE OCCUPYING to manage raised intracranial pressure are listed in
LESIONS AND HYDROCEPHALUS Table 19.18.
Intracranial pressure refers to the pressure of CSF within Space Occupying Lesions
the cranium. It is normally pulsatile and less than 5 mm Hg
Brain Tumors
in newborns, 6-15 mm Hg in infants and 10-15 mm Hg in
older children. Intracranial pressure is considered severely Primary brain tumors are the second most common
elevated, if raised above 40 mm Hg. malignancy in childhood after leukemia, and may be
malignant or benign. Their incidence is increased in
Pathophyslology neurocutaneous syndromes like tuberous sclerosis and
Raised intracranial pressure results in decreased cerebral neurofibromatosis. Tumors present chiefly with focal
blood flow and/or herniation of brain tissue. Cerebral neurological deficits and symptoms of raised intracranial
blood flow is normally about 50 mL per 100 g of brain pressure. Two-thirds of pediatric brain tumors are
tissue per minute and depends on cerebra.I perfusion infratentorial. Of these, medulloblastoma and cerebel.lar
pressure, the difference between mean arte~ial pressu~e astrocytomas account for a third each while brainstem
and intracranial pressure. Various m~ogemc, met~bol.1c gliomas and ependymomas constitute U1e majority of the
and neurogenic autoregulatory mecharusms help main tam rest. Since the posterior fossa is tightly encased with
cerebral blood flow. Decrease in cerebral blood flow to narrow CSF pathways, infratentorial tumors present with
below 40% leads to progressive ischemia, ~e~ronal dea~h, raised intracranial pressure and hydrocephalus. Common
cerebral edema and further increase m mtracranial supratentorial tumors include astrocytomas, cranio-
pressure, leading to diffuse bilateral cortical dysfun~tion pharyngioma, ependymomas, choroid plexus papillomas
and coma. Causes of raised intracranial pressure are hsted and pineal body tumors. Neuroimaging by MRI helps
in Table 19.16 and common causes are discussed below. define the nature and extent of tumor.
• 576 Essential Pediatrics
I
contralateral lower limb
Lateral transtentorial Downward and medial displacement of uncus Unilateral dilated pupil with ptosis (third nerve
and parahippocampal gyrus palsy); impaired consciousness; abnormal
respiration; hemiparesis
Central transtentorial Downward displacement of diencephalic structures Impaired consciousness; abnormal respiration;
symmetrical small reactive or midposition fixed
reactive pupils; decorticate followed by
decerebrate posturing
Upward transtentorial Upward displacement of cerebellar vermis and Prominent brainstem signs; downward gaze
midbrain deviation; decerebrate posturing
Transforaminal Downward displacement of cerebellar tonsils Neck rigidity; impaired consciousness;
and medulla ophisthotonus; decerebrate rigidity; vomiting;
irregular respiration; apnea; bradycardia
. ,.
_ Table ~. 9.18: Management of raised intracranial pressure pediatric posterior fossa tumors. Boys are affected
2-4 times as often than girls. These rapid ly growing,
Raise head end by 30 degrees; keep head in midline
malignant tumors present with cerebellar signs and
Hyperventilate to maintain PC02 at 30-35 mm Hg features of raised intracranial pressure. Neuroimaging
Administer mannitol at 0.25-1 g/kg (1.25-5 mUkg of 20% reveals a midline mass arising from the vermis, effacing
solution) as intravenous (IV) bolus; repeat every 8 hours for the fourth ventricle and basal cisterns, causing obstructive
48-72 hours hydrocephalus (Fig. 19.lla). The tumors a re usually
Administer hypertonic (3%) saline at 0.1-1 mUkg/hr to maintain hyperdense with prominent enhancement (90%) and
serum sodium at 145-155 mEq/L associated with cysts or necrosis (40-50%) or calcification
Administer IV furosemide at 1-2 mg/kg/dose (10-20%). Forty percent of patients have evidence of CSF
Switch to oral acetazolamide or glycerol when stable seeding at diagnosis. The prognosis is poor.
Consider corticosteroids (oral or IV) for vasogenic edema Cerebellar astrocytoma: These arise from either cerebellar
Consider decompressive craniectomy hemispheres, and present with ataxia, incoordination m d
nystagrnus. Most tumors are low-grade and slow-gro\\·ing
Medulloblastoma: These midline cerebellar tumors and carry a satisfactory prognosis as they can usuall~- be
usually affect young children, accounting for 30-40% of excised completely.
Rg. 19.11: Contrast enhanced tomography In the setting of raised intracranial tension showing (a) Enhancing heterogenous mas~
arising from vermis suggesting medulloblastoma; (b) Left parietal enhancing lesion with midline shift In a case of brain abscess.
and (c) Multiple basal ring enhancing lestons and meningeal enhancement in a patient with tubercular meningitis
Diseases of Central Nervous System
I sn •
Brainstem gliom~: These usually present between 5 and surrounding edema. Large lesions show mass effect,
1~ years of age wit~ lower cranial nerve palsies, long tract
signs, cerebe~lar signs and signs of raised intracranial
pre~su~e. ~le bo~ focal brainstem gliomas and diffuse
intrmsic ponhne ghoma carry grave prognosis, the latter
have worse outcomes.
distortion of surrounding structures and midline shift
(Fig. 19.llb). CSF may show mild pleocytosis due to
meningeal reaction; however, lumbar puncture is usually
contraindicated because of risk of herniation. Management
includes administration of intravenous antibiotics with
I I
Ependymoma of tlte fourth ventricle: These arise from cells good penetration into the CSF for 4-8 weeks. Anaerobic
lining the v~ntricle. Tumors arising from the floor of the coverage must be ensured. A third-generation cephalo-
fourth ventricle present with torticollis and ataxia while sporin with vancomycin and metronidazole provides
those arising from the side of the ventricle affect ~ranial satisfactory empiric coverage. Drainage of the abscess
nerve~, presenting with impaired hearing, dysphagia and must be done through burr hole, craniectomy, craniotomy
clumsiness. or by stereotactic aspiration.
Cranioph~n!ngioma: These are cystic benign supratentorial Subdural Collectlons
tumors ansmg from the squamous epithelial rest cells of
~e RatI:I<e pouch. C~ical features include growth failure,
Subdural collections usually occur as a complication of
visual field d~fe~ts (b1temporal hemianopsia or unilateral bacterial meningitis, chiefly in infancy. Subdural
or asymmetric field defects), signs of raised intracranial effusions are usually sterile and resolves spontaneously;
pressure and endocrine abnormalities like diabetes drainage is only necessary if associated with pressure
effect. They may, however, be associated with prolonged
insii:>i~us. and delayed puberty. X-ray skull may reveal
calcificat10ns. Treatment includes cyst aspiration and fever. Subdural empyemas are collections of pus in
radiotherapy. subdural spaces and are detected on imaging by an
enhancing capsule. They usually require drainage but may
Glioma of cerebral hemispheres: These usually present refill. Subdural hematomas are usually traumatic and
with seizures and hemiparesis; features of raised present with features of chronically raised intracranial
intracranial pressure are usually delayed. Histologically, pressure. A vascular membrane forms around the
these may be astrocytoma, oligodendroglioma or hematoma. As blood cells get absorbed, the fluid's protein
glioblastoma. content increases, thus increasing oncotic pressure that
Glioma of optic nerve: These relatively uncommon tumors draws fluid into the hematoma. The collection grows,
usually occur in a setting of NFl and present with tearing small bridging veins within the hema toma, further
decreased vision, and later with proptosis, symptoms of increasing bleeding. The sequence of bleeding, increased
raised intracranial pressure, focal neurological deficits and pressure and growth repeats itself. The skull mav show
hydrocephalus. Hypothalamic involvement may result in positive transillumination. Imaging reveals a bi~onvex
polyuria and polydipsia. Imaging indicates an enlarged collection, as compared to the crescent shape seen with
optic nerve. epidural collections.
Management
The first priority in managing coma is ensuring that Clinic~/ criteria: Complete loss of conciousness, vocalization
airway, breathing and circulation are maintained. Spe~c and volitional activity
I
therapy is administered where available. Supportive Absent bralnstem reflexes: Absence of all of the following:
treatment includes antipyretics for fever, anticonvulsants Pupillary responses to light (with pupils midposition, 4-6 mm)
for seizures, and measures to manage raised intracranial
Oculocephalic reflex
pressure (Table 19.18). Sedative anticonvulsants are
Oculovestibular (caloric) responses
avoided to prevent interference with evaluation of depth
of coma. Appropriate nursing is essential in improving Corneal reflex
outcomes during prolonged coma, and includes chest Jaw reflex
physiotherapy to prevent hypostatic pneumonia, adequate Facial grimacing to deep pressure on supraorbital ridge or
nutrition, care of the skin and eyes to prevent bedsores, temporomandibular joint
corneal ulceration and exposure keratitis, care of the bowel Pharyngeal gag reflex
and bladder to prevent constipation, fecal impaction and Coughing in response to tracheal suctioning
urinary tract infection, and physiotherapy to prevent deep Sucking and rooting reflexes
vein thrombosis and contractures. Apnea: Absence of respiratory drive at PaC02 of 60 mm Hg
The patient should be placed in lateral head down or 20 mm Hg above baseline
position with frequent changes from side to side. This Prerequisites
position-also called the 'recovery' (from anesthesia) Clinical and/or neuroimaging evidence of acute CNS
position reduces obstruction to breathing from tongue catastrophe severe enough to explain the condition
falling back, protects against hypostatic pneumonia by Core temperature more than 32°C"
facilitating drainage from lungs and guards somewhat
No drug (sedatives, narcotics) or alcohol intoxication,
against aspiration. poisoning or neuromuscular blockade
Persistent Vegetative State Normal blood pressure
No confounding conditions such as severe electrolyte, acid-
This term refers to a state after recovery from coma when base, metabolic or endocrine disturbances
the patient returns to a wakeful state with preserved sleep Two evaluations, separated by a time interval of 48 hours, if
wake cycle but without any awareness. <2 months old; 24 hours, if 2-12 months old; 12 hours, if 1-18
years old; and at any interval, if > 18 years old
Brain Death
Ancil/iary tests: Two tests required if <2-month-old; one test
This term refers to complete cessation of all brain function if 2-12-month-old; tests optional if >1 year old""
including the brainstem. Criteria for brain death are listed Cerebral angiography
in Table 19.22. The proximate cause of brain death should Electroencephalography
be known and the condition should be irreversible, with
Transcranial Doppler ultrasonography
potentially reversible causes excluded, including use of
Cerebral scintigraphy
CNS depressants, hypothermia, shock, and metabolic and
endocrine disturbances. All brainstem reflexes should be •Adapted from American Academy of Pediatrics. Task Force on ?rain
absent with apnea. Since brains of young infants have Death in Children 2011, and the American Academy of Neuro:ogy,
Practice Parameters for the Clinical Diagnosis of Brain Death; and
increased resistance to damage, longer observation
consistent with the Indian Transplant of Human Organs {THO) Ac:, 201 4
periods and ancillary tests are reconunended in this group. "35°C according to the THO act
Two independent physicians must conduct a full lwo tests 6 hours apart at all ages according to the THO Act
examination twice at the recommended time interval. The
apnea test should be performed by disconnecting the Suggested Reading
patient from the ventilator after achieving normal blood
gas, allowing arterial carbon dioxide to rise to 60 mm Hg • Act and Rules under Transplant of Human Organs Act (I1IOA)
Transplantation of Human Organs and Tissues Rul es, 20H;
or 20 mm Hg above baseline; absence of respiratory effort available at notto.nic.in/ act-end-rules-of-thoa.hbn.
(positive apnea test) is consistent with brain death. • Nakagawa et al. Guidelines for the determination of brain death
It is possible to sustain life on life support systems in infants and children: An update of the 1987 Task Force
sometimes indefinitely even after brain death but the indi- recommendations. Critical Care Medicine. 2011; 39: 2139-55.
vidual can never return to a functional state. The diagnosis • Taylor DA, Ashwal S. Impairment of consciousness and coma. In~
Swaiman KF, Ashwal S, Ferriera DM. eds. Pediatric neurology.
of brain death is important in deciding to discontinue the
principles and practice.5th ed. Philadelphia: Elsevier Publications;
life support systems and also for organ transplantation.
2006. p. 1379-1400. ·id
Different countries have their own laws and criteria for • Sharma S, Kochar GS, Sankhyan N, Gulati S. Approach to the chi
diagnosis of brain death. with coma. Indian J Pediatr.2010; 77:1279-87.
20
Neuromuscular Disorders
Sheffali Gulati
A motor_ unit comprises one anterior horn cell and all the Inflammatory disorders such as dermatornyositis are
muscle fibers that it innervates · Neuromuscu1ar d isor
" d ers associated with waxing and waning course and pain.
may be. dued to lesions anywhere along the mo tor uru·t. Cardiac disease often accompanies Duchenne muscular
These me1u e neuronopathies (disorders of anterior horn dystrophy, Pompes disease and myotonic dystrophy. Skin
cell), neuropathi~s (d~sorders of axon or its myelin), rash is seen in dermatomyositis; eyes are involved in
n~uromuscular JUnchon disorders and myopathies myotonic dystrophy, congenital muscle dystrophies and
(disorders of muscle). mitochondrial diseases. Liver involvement may be seen
with mitochondrial disorders, acid maltase deficiency and
APPROACH TO EVALUATION carnitine deficiency.
The predominant presenting complaint of a patient with Laboratory Evaluation
a neuromuscular disorder is weakness. Weakness may
also result from disorders of the upper motor neuron, e.g. Creatine _phosphokinase (CPK), a muscle enzyme, is
cerebral palsy. Weakness due to an upper motor neuron elevated m most muscular dystrophies. Muscle biopsy
lesion is associated with increased tone, brisk reflexes and enables diagnosis based on specific morphological
extensor plantar responses. Additional features that features, immunohistochemistry (absent or reduced
suggest central nervous system involvement include staining for specific protein) and enzyme histochemistry
decrease in level of consiousness, seizures and cognitive (absent ?r redw~ed enzyme function). Electrophysiological
tests, mcludmg nerve conduction s tudies and
impairment.
Lower motor neuron lesions are associated with electromyography, help localize the lesion and assess its
severity. Muscle imaging (ultrasound and MRI) is useful
significant weakness, hypotonia, depressed reflexes and
in certain cases. Molecular genetic testing is available for
flexor plantar responses. Anterior horn cell involvement
many disorders, including spinal muscular atrophy and
(e.g. spinal muscular atrophy) is associated with
Duchenne muscular dystrophy.
generalized weakness and wasting, fasciculations and
hyporeflexia. Peripheral nerve involvement (e.g. hereditary Hypotonia
sensory and motor neuropathies) is associated with
predominantly distal weakness and wasting, hyporeflexia Hypotonia is a common sign of neuromuscular disorders.
and sensory involvement. Neuromuscular junction Any les~on along the motor unit can result in periplreral
involvement (e.g. myasthenia gravis) leads to fatigable and hypotonza, characterized by depressed muscle stretch
fluctuating weakness. Muscle diseases (e.g. muscular reflexes and loss of muscle power. The common causes of
floppiness in infants are shown in Fig. 20.1. Hypotonia in
dystrophies) present with proximal weakness and
utero may result in hip dislocation or multiple contractures
relatively preserved bulk and reflexes. The mode of
(arthrogn;posis). The mother may give a history of reduced
inheritance is variable, e.g. X-linked recessive in Duchenne
fetal movements or polyhydramnios.
tnuscular dystrophy and Becker muscular dystrophy;
autosomal dominant in facioscapulohumeral dystrophy; An alert hypotonic infant with absent deep tendon
and autosomal recessive in sarcoglycanopathies and reflexes, predominantly distal movements and
fasciculations is the typical phenotype of spinal muscular
congenital muscular dystrophies.
The presentation and pattern of disease over time atrophy. Neuropathies usually present later in childhood.
allows definition of possible conditions. Muscular Atrophy out of proportion to weakness, depressed or
dystrophy is associated with inexorabl~ weak~es~. absent reflexes and predominantly distal weakness
Metabolic disease and ion channelopathies (penod1c suggests a nerve disorder. Fatigability, ptosis, proximal
paralysis) are associated with episodic course. muscle weakness and history of myasthenia gravis in the
581
-582 I Essential Pediatrics
Central Hypotonia
Neurometabolic conditions
Chromosomal disorders
Prader-Willi syndrome; trisomies Acid maltase deficiency
Biotinidase deficiency
Static insult GM1/GM2 gangliosidosis
Cerebral malformations Lowe syndrome
Perinatal insult Peroxisomal disorders
Familial dysautonomla
Infections
Sepsis/Meningitis; intrauterine infections Benign congenital hypotonia
Peripheral Hypotonia
Neuromuscular junction
Congenital myasthenia
Transitory myasthenia
Botulism
Fig. 20.1: Common causes of 'floppy Infant'. Maintenance of normal tone requires on intact central and peripheral nervous
system
mother suggest a neuromuscular junction disorder. • McDonald CM. Clinical approach to the diagnostic evaluation of
Predominantly proximal muscle weakness, normal or hereditrary and acquired neuromuscular diseases. Physic,11
medicine and rehabilitation clinics of North America. 2012;
depressed tendon reflexes and static or improving course 23(3):495-563.
indicate a muscle disease. Deep tendon reflexes are
preserved in muscle disease or, if reduced, are in Muscle Weakness In Older Children
proportion to the degree of muscle wasting and weakness.
Distal weakness is predominantly seen in neuropathies
Atrophy is less prominent in muscle disorders.
and ~ome muscle disorders like myotonic dystrophy.
Central l1ypoto11ia is characterized by preserved muscle Proximal weakness has broad differential diagnosis
power and normal or brisk deep tendon reflexes. (Fig. 20.2). The child may complain of difficulty in risirlg
Sometimes patients may display features of both central from the chair, going up and down the stairs or reaching
and peripheral hypotonias; common causes of mixed with their arms. Some disorders such as chronic
l1ypotonia include hypothyroidism, motor unit disorders inflammatory demyelinating polyneuropathy (CIDP) and
with superimposed hypoxia, acid maltase deficiency, certain muscle dystrophies show both proximal and distal
mitochondrial disorders and infantile neuronal weaknesses.
degeneration.
DISORDERS AFFECTING ANTERIOR HORN CELLS
Mixed l1ypoto11ia: Features of both central and peripheral
hypotonias as in lysosomal storage disorders, Spinal muscular atrophy and poliomyelitis are the MO
mitochondrial disorders and peroxisomal disorders. most common anterior horn cell disorders in children.
Besides these, other enteroviruses (e.g. coxsackievirus and
Suggested Reading echovirus), juvenile form of amyotrophic lateral sclerosis,
• Ahmed Ml, Iqbal M, Hussain N. A structured approach to the and neurometabolic disorders like Tay-Sach disease,
assessment of a floppy neonate. Journal of Pediatric Neurosciences. neuronal ceroid lipofuscinosis and Pompe disease, may
2016;11(1):2-6. also involve anterior horn cells.
• Jan M. The hypotonic infant: Clinical approach. Journal of Pediatric
Neurology 5 (2007) 181- 187. Spinal Muscular Atrophy
• Darras BT, Jones HR Jr, Ryan MM, et at., 2015. Neuromuscular
disorders of Infancy, Chlldhood and Aldolesence:A clinician This is an autosomal recessive disease caused by a
Approach 2nd ed.Elsevler, London. mutation in the SMNl gene at chromosome 5q13.2 region.
ls83 -
Proximal muscle weakneH I
+
Absentdeeptendonreftexes
.. I
+ ...
!Progressive disorder! Reduced or absent Ptosls
Fasciculations ± calf hypertrophy deep tendon reftexes Ophthalmoplegla
Tremors Faligability
Contractures
Static course Facial weakness Diurnal variation
1 Static course
... l
ISpinaI muscular atrophy j IMuscular dystrophy I IMyopalhy I j Neuromuscular junction disorders j
•
I
...
Rash Dynamic findings
Systemic features Episodic worsening
This region also carries SMN2 gene, the copy number of present later in childhood (> 18 months) and are usually
which acts as a main modifier of the various clinical able to walk. These children are often misdiagnosed as limb
phenotypes encoding the SMN protein of anterior motor girdle muscular d ystrophy or myopathy. Global areflexia,
horn cells. Four clinical types are recognized. Type 0: It is fasciculations, polyminimyoclonus and tremors gh·e a clue
the most severe form and presents in the fetal life. Most towards Wlderlying anterior horn cell p athology.
children do not survive. Patients with type 1 disease Treatment is supportive and includes respiratory care,
(Werdnig-Hoffmann disease) present with profound management of problems in feeding and swallowing,
hypotonia, fla ccid weakness and global areflexia ensuring adequate nutrition, treatment for g a s tro-
(Fig. 20.3). Respiratory weakness, poor swallowing and esophageal reflux, orthopedic care and rehabilitation,
tongue fasciculations are common. These children usually appropriate immunization and family educa tion a nd
never learn to sit. Aspiration pnewnonia is an important counseling. Newer genetic based therapies haYe been
cause of morbidity and mortality. Patients with type 2 developed for SMA like SMN 1 gene replacement
disease (Dubowitz disease) have onset of illness at 6--18 therapy and SM1'J2 upregulation/modification. Spinraza
months of age and are usually able to sit unaided. They (Nusinersen) is an antisense oligonucleotide and is the first
may develop kyphoscoliosis, tremors (polyminimyo- disease modifying therapy approv ed for S~l A. It has
clonus), poor swallowing and respiratory insufficiency. shown significant benefits in these patients, but needs
Patients with type 3 disease (Kugelberg Welander disease) repeated intrathecal administrations.
Suggested Reading
• Darras BT, Markowitz JA, Monani UR, et al. Spinal muscular
atrophied: A clinical approach, second ed. Academic Press, S.:in
Diego 2015: 117-145.
• Faravelli I, Nizzardo M, Comi PG, Corti S. Spinal mmcubr
atrophy-recent therapeutic advances for an old challen!:~· Nat
Rev Neural 2015; 11: 351-359.
• Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscul.u
atrophy: controversies and challenges. Lancet Neurol ~0 1 ~ 11:
443-52.
• Patient Education Leaflets on SMA; available at http:/ / aiims.edu /
aiims/ departments/pediatrics/ ped_neuro I patiented u.htm
• Seo to M, Finkel RS, Mercuri E, MWltoni F. Therapeutic appro.lcht-s
for spinal muscular atrophy (S!\L\). Gene Ther. Wli Sep; 24(<)):
514-9.
PERIPHERAL NEUROPATHIES
Fig. 20.3: A 5-month-old boy with motor delay and repeated Most neuropathies are chronic. Guillain-Barre syndrome
Chest Infections. shows generalized hypotonla. absent deep is the most common cause of acute neuropathy. Oinical
tendon reflexes. poor muscle power and tongue fasclculatlons.
features, presentation, electrophysiological characteristics
Note the 'frog-Ilka' posture and subcostal retractions due to
respiratory muscle weakness. A diagnosis of spinal muscular and laboratory studies help in evaluating the diagnosis
atrophy type 1 was made (Fig. 20.4).
-sa4 I Essential Pediatrics
...
IDemyelinallng J
"' I
I Axonal
!
I Pattern I
• Acqulrod
.
AtDP orCIDP
Diphtheria
Toxic, e.g. arsenic
Hereditary •
Charcot-Marle-Tooth
disease 1 and 3
Metachromatic
leukodystrophy
Krabbe disease
•
Mononeuropathy
t
I •
Asymmetric with
stepwise progression
Mononeurltls multiplex•
i
..
Polyneuropalhy
(involvement of ~2 nerves)1
1
j
Table 20.2: Diagnostic criteria for Gulllaln-Barre syndrome Initiative, AFP is defined as any case of AFP in children
Features required for diagnosis <15-year·old, or any paralytic illness at any age when polio
is suspected. Common causes of AFP include Guillain-
Progressive weakness In more than 1 llmb (usually starts In
legs) Barr~ syndrome, poliomyelitis, transverse myelitis
traumatic neuritis, postdiphtheric neuropathy and
Arellexla (or decreased tendon reflexes) In weak llmbs
nonpolio enteroviral illnesses. The differential diagnosis
Features that strongly support diagnosis varies with age (Table 20.3); distinguishing features are
transportation of stool specimens for laboratory testing, A case is classified as 110/io, if wild poliovirus is isoln ted
search for additional cases and outbreak investigation in from the stool specimen. Cases with in<1dequatc s tool
the affected community, 60 days follow-up examination, specimens and ha\'ing residual we.1kness \vho h;l\ e dil~d
analysis of laboratory results and case classification. or are lost to follow up undergo additional in\'cstigntion
Collection of stool specimens from e\'ery patient is an and are presented for re\'it•w by the Nnti onn l Expert
important aspect of the eradication strategy. From every Review Committee. This committl'e classi fies the c.,Sl' ,,s
case of AFP, two stool specimens are collected, ideally compatible wit11 polio or disc11r1frd 11s 11 011-pci/io AFP.
within 14 days of onset of paralysis and at least 24 hours Experience indicates thnt .1t least 1 c,1se of non-polio AFP
apart. While the optimal period for detection of poliovirus occurs for e\'ery 100 000 children aged <15 Yl'.ns pl'r )'l',1r
in the stool is within 14 days of onset of paralysis, specimens (background AFP r.1te). As pl'I' Nntional Polio Surwilbnl'C
may be collected from any late-reported case up to 60 days Project, the non polio Al~P rate, which is nn indic.ltor of
from the onset of paralysis. Beyond 60 days after paralysis, sunreillance sensitiYity should be equnl or to more than
1:100, 000.
the likelihood of detecting poliovirus is very low. Voided
stool sample, is preferred. In cases '•:here it is not po~ibl~, Suggested Reading
other methods include digital extraction (when child is
constipated or dies), postmortem stool collection (contents • Chatterjee A, \lidpnll', Dhol~ TN. J\,Ji,, r.u11ic.1tion in ln.t i.1.
Vaccine 2013;18: 1:'!6~-75.
of large intestine) and use of rectal tub~. Enema or • Smveiltmce of neut,~ ll.1ccid p1H.1ly:;i~ . :11'1.\ 1,ln. N1•w O..'lhi: t\li11btry
purgatives are not recommended. Each speomen sho~d of HealU1 & family \\'df.m.', G1w1•mnwnt of ln11i.1: ~0(1,'\
be8 geach (about the size of one adult thumb), c~llected m
a dean dry screw-capped container. The specunens are NEUROMUSCULAR JUNCTION DISORDERS
collect;d, labeled and then transported in the 'cold chain'.
Disorders affecting the nt•unm1uscul.u· jlltll' tion c.m bl'
Two types of cell lines are used for poliovirus isolation.
acquired or inherited (Tilble 20.S). They arl' usti.llly put\.'
The human rhabdomyosarcoma (RD) ce~l lines favor
motor syndromes nffcctin~ pm:-..im.11, bulb.um t'\.h\locul.lr
growth of all enteroviruses, and L20B cell Imes favor the
muscles.
growth of only polioviruses. lf cytopathic effects ?PP~ar
in L20B cell line, the isolate then goes for neutrahzat~on Myasthenla Gravis
test to determine the serotype (type 1.' :: or. 3) usmg
appropna · te an tiS'era . Intratypic differentiation About 20% patients with mynstlwnin lHWt' onset in
r 1s.done hto
determine, if the isolate is wild or vaccin~ po tovirus; t e childhood or ndolcsccnct'. Fntig11blt• wc1\knes~ is tlw
, former isolates undergo genetic sequencing. hallmark. ~fost patients h,we ptosis or ophthnlmnpll'hl.1
-oeo I Essential Pediatrics
wh ich may be asymmetric and variable o ver time. of the clinical sign (ptosis, ophthalrnoplegia, dysarthria)
l'upllb1Ty reactions arc normal. Children may develop under observation. Edrophonium is not recommended for
dlplopla on HUbta incd gaze or continuous activity like use in infants due to high risk of arrhythmias and short
ret1di111;. O n attempting to tightly d ose the eyes, after a duration of action which precludes objective assessment.
fl'w 1nJ11uleH, the cornea may get exposed due to inability Neostigmine may also be used as a diagnostic test. The d05e
lo 1111 ~1a Jn conlraclion of orbicularis oculi (peep sign). used is 0.125 mg/kg in an infant and 0.04 mg/kg TM in an
About half of the children with ocular findings may older child. It is slower in action, with anticipated response
u1•v1•lo p b ulbar or llmb girdle weakness within 2 years. in 10-15 min and maximum in 30 min (Fig. 20.6). If the
lh1lh.ir wc;.1 km~!J~ may ma nifes t in form of difficulty in result is equivocal or negative, the dose may be repeated
•- 11wallowing ;ind chewing and nasal and slurred speech. in 4 hours.
1.lmh wc·ak11c11s is usually symmetric and proximal. Deep
Repetitive neroe stimulation studies are abnormal in
ll'lldw1 n •n cxcH nrc either normal or reduced in proportion
50-70% cases with generalized myasthenia gravis. A
lo tlw dt·grec of muscle wc<1kncss. Respiratory muscles
111ay ahm get involved and may lead to myasthenic crises. decrement of >10% is characteristic. Electromyography
My.111the11ia gravis may be associated with thyroid dis- may be normal or may show unstable or myopathic
orderM, Mys temic lupus crythcmatosus, diabetes mellitus muscle unit action potentials. Single fiber electromyo-
and rhc uinilloitl arthritis. Thymomas are found chiefly in graphy is more sensitive and may show increased jitter
adoll'M c'cnt onset myas thenia grnvis and are ra re (<5%) in or blocking.
ea rly childhood. Acetylcholine receptor (AChR) antibodies may be positive
'l'runsltory lll!o11atal myt1slftenia occurs in about 15% of in children with myasthenia gravis; the rates are lower in
bnbi< H born lo myasthenic mothers. Symptoms start within
1 peri- and prepubertal children (50-60%). Antibodies to
11 few hours after birth but may be delayed till the third muscle-specific kinase (Anti-MuSK) are seen in -10%
duy. Thcf'! c include difficulty in feeding, weak cry, seronegative patients. X-ray chest or CT of anterior
hypolonia, lack of facial expression and respiratory mediastinum may show thymoma or thymic hyperplasia.
lnti uffidcncy. Supportive care suffices in most cases. Oral Congenital Myasthenla Syndromes
or J11lrn111u1:>culi1r pyridostigmine, usually for 4-6 weeks,
1rn1y be wnrr<111t~d in severe cases. The congenital myasthenia syndromes are exceptionally
rare ..They sho~d be suspected in seronegative m yas thenia
l :dro11fw11i11111 ftosti11g is usually the first test performed in ?rav1s, flopr y infant with underdeveloped muscles and
o flll8pcclcd cnsc of myasthenia gravi s. The dose used is m adults with childhood history of difficulties affectin(7
(l.'1 - 0.2 mg/kg; may be repeated every minute to a total cranial, respiratory, truncal or limb muscles. Commo~
dm1c of 5 mg (weight <34 kg) or 10 mg (weight >34 kg). feat~res incl~d.e hypotonia, limb weakness, feeding and
12ffoc h; ore Hccn within 10 seconds and persist till 120 resp1r.atory d1ff1c~lhes, arthrogryposis, ptosis, ophthalmo-
1:1cconds. A positive result consists of trnnsient resolution pares1s, .dysphag1a and dysarthria. They do not respond
t? steroids and other immunosuppressants. Cond itioPS
· !nblo 20.5: Neuromuscular junction disorders In children ' hke endplate ace~lcholinesterase deficiency and slL'w
. lmmuno modlated Metabolic causes channel congenital myasthenia may worsen with
Myasthenla gravts Botulism pyridostigmine.
Lambert-Eaton myasthenlc Organophosphate Treatment
syndrome poisoning
Congonltal myesthenlc Snake envenomatlon Cholinesterase inhibitors are the initial treatment for
eyndromos Tick paralysis myasthenia gravis. Pyridostigmine is commonly used at
Chollno acetyltransferase Hypermagnesemla doses of 1-7 mg/kg/ day in 4 divided doses. Prednisolone,
doflclency Drugs at low doses (0.5 mg/kg/ d), may be used in a nonacute
Paucity of synaptic vesicles Amlnoglycosldes setting. Azathioprine, cyclosporine, cyclophosphamide
Endplate acetyl- Erythromycln and mycophenolate mofetil are used as steroid sp:iring
cholinesterase deficiency Tetracycline drugs or for refractory cases. Drugs that interfere with
Acetylchollna receptor Fluoroqulnolones neuromuscular transmission (Table 20.4) should be used
defects with caution. Thymectomy is beneficial in seropositive
Mutations In rapsyn or Neuromuscular blocking patients.
plectln agents A rnyasthenic crisis necess itates ca rdiorespiratory
Phenytoln .
Dok·7 deficiency D·penlclllamlne monitoring and support. It should be differentiated from
Lithium cholinergic crises due to overdosage of acetykholin-
Interferon a esterase inhibitors. Antecedent events, predominance of
cholinergic symptoms, ice pack test and edrophonium
Neuromuscular Disorders I sag -
Fig. 20.6: Juvenile myasthenla gravis: A 9-year-old boy presented with drooping of eyelids, more in the evening than morning, and
restricted eye movements. Examination revealed asymmetric ptosls, external ophtholmoplegia, normal pupils and normal motor
examination. Note the improved ptosls (a) before and (bl after administration of neostigmine
challenge test help differentiate the two entities. IVIG or Suggested Reading
plasmapheresis may be required in patients with • North NK, Wang HC, Clarke N, et al. Approach to the diagnosis
myasthenic crisis. of congenital myopathies. Neuromuscular Dis 2014; 24:97-116.
• Wang HC, Dowling JM, North K, et al. Consensus statement on
Suggested Reading standard of care for congenital myopathies. J Child Neurol 2012;
• Castro D, Derisavifard, S, Anderson, M, et al. Juvenile myaesthenia 27;363.
gravis: a twenty year experience. J Clin Neuromuscular. Dis 2013;
14, 95-102. Muscle Dystrophles
• Sanders DB, Wolfe GI, Benatar M, et al. International consensus
guidelines for management of myasthenia gravis. Neurology 2016; The muscular dystrophies are diseases of muscle membrane
87:419-25. or supporting proteins characterized by patholoo-ical
evidence of ongoing muscle degeneration and reg~era
MUSCLE DISORDERS tion. Diagnosis of these disorders is based on clinical presen-
Congenital Myopathles tation, genetic testing, muscle biopsy and muscle imaging.
The congenital myopathies are a diverse group of muscle
Dystrophlnopath/es
disorders caused by genetic defects in the contractile
apparatus of the muscle and defined by distinctive Dystrophin?pat~ies are a group of disorders resulting
histochemical or ultrastructural changes on muscle biopsy. from mutations m the dystrophin gene (located on short
Majority of these disorders present as 'floppy infant' arm of X chromosome, Xp21). Duchenne muscular
syndrome. The common presenting features include dystrophy is the most common dystrophinopathy with
hypotonia, static or non-progressive muscle weakn~ss and an incidence of 1in3500 live male births. Its allelic variant,
normal or decreased deep tendon reflexes. Respiratory Becker muscular d ystrophy, differs by a later onset
insufficiency, feeding difficulties, contractures and s~eletal (usually >6 years old), and slower progression (wheel-
deformities may be present. They may also present m late chair confinement >15 years), a higher incidence of
childhood or adulthood (Table 20.6). myalgias, occasional rhabdomyolysis following exercise
Serum creatine kinase is either normal or mildly raised. and early cardiomyopathy.
Electromyography reveals a myopathic p~t~ern." T~e Over 4700 mutations are reported in the Leiden
disorders are clinically indistinguishable; distmch.on is Duchenne dystrophy database. 65% of the pathogenic
possible by characteristic features on sk~letal mus~le biopsy changes are large partial deletions. Mutations in the
incorporating new immunohistocheIDical techniq~es and dystrophin gene can cause Duchenne muscular dystrophy
electron microscopy. Advances in molec~lar genetics .h ave or Becker muscular dystrophy. The phenotypic variation
improved our understanding of congerutal myopathies. is explained by the reading frame hypothesis. In >90% of
-sgo 1 E11onllnl Pediatric•
cases, mutations that disrupt the reading frame (fr.unc: prol>c amplHlr.1t l11n (Ml.PA) i1r1• 11r.t·tl fur tl1·tt·f!l11t1 ,,,
shift) lead to dystrophin deficiency and cause Duchcnne mutations. Musrl1· hl11p.. y 111.1y lw rc·1111ir1•cl in rn111.11111n
dystrophy. In Becker dystrophy, mutations maintain the ncgntivc CJ St'S allld lo d ilfl•r1•11 Ii11l1• lw h vn ·n 1)11dwru '" .ind
reading frame (inframe mutations) and result in abnormnl Decker dystrophy. lli11p1.y 11 hmv ~1 1wu11.,h Mid .11t1·t11J1lr1I
but partly functional dystrophin. rcgcncr.1tio11 of lndlvid11.1l 1111l'1cl1· fi l>c·r". v.1rl.1bl1· 11 11 1 ·• f..-
Children with Duchcnnc dystrophy become fibcr dianwh'r with h11tl1 hyp1·rtrnph h .111d 'lm.111 f1b~-t1 ,
symptomatic before age of 5 years and may have history and ccntr.11 n11d1•I. l..11i-r, .1111111 ~ 1 Iha· 1·11tir1· mu ,, Ir ''
of delayed walking. Gait disturbances become apparent replaced hy flhrof.111 y 1 1~.-. 111 " ( l11 i1111111111nhh t11d ,·1111,1r,.
at 34 years of age. Wnddling gait, Gower sign .ind calf nbsenccof drtrophln (I , 2, '.' ) ,.. 1.t111 i 11>~ i-. -..·,·n 111r111dw 1 ··('
muscle pseudohypcrtrophy (Fig. 20.7) arc classical dystrophy; dystrophln 11t11i11ing h rl'd11n·d .md p.tt. h·, r1
findings. Weakness of neck flcxors is early. Other muscles Decker dystrophy.
that show hypertrophy include vastus laternlis, Mm111gc1111·11t: Pillil•nl !'I with I >11 h1·11m• d y:"\trnph\ rr1p11r..,
infraspinatus, deltoid, gluteus maximus, triceps ilnd
mullidisclplinnry mi\n11ht'ml·t1t, .1lm l n ~~ for m.llnh'n it'•··• r
masseter. The progression of weaknl!ss mily plateau
muscle strength and rnt1gl' 11( 111nlllln of joinh h\' '"'' 11 '"·
between 3 and 6 years of age, followed by incre.1sing gait physiotherapy and avoid,111 1• of pnil11 n~t·d 1n1111 1~'• ' t•,
difficulty, development of contrnctures and lumbar Corticosteroids (pn•d11h.011t•, d1·fl.v.tnir t} .u1· th·. , rilv
lordosis. The age ,1t Joss of independent ambulation in
therapies proven lo lmprov1• ~ t r 1· n >; th .md pr. ·: ~ .~
untreated patients is between 8.8 and 10.5 years. After loss ambulation in childn•n w ith th1• d i.,1'.1w. I o\• I· ·<:
of ambulation, there is worsening kyphoscoliosis,
prcdnisolo11c 111.1y IH· :-.1.irll·d wilh .1 i111 111 l'h"1·n wi; 11;, ··t
increasing upper limb weakness nnd bulbar dysfunction. limb strength, rl•d11 d 11g p n •>; r1•.,.,lon ,1 j .,,·,>11.1 " , u1.l
Weakness of intercostal and diaphragmatic muscles delaying ch•clirw i11 n·spir.1tmy .rnd 1".1rd1.1.: tutt ! ., ..
with spinal deformity affects respiratory function. Supportive m .m;i~;l'nwnl .1IM1 i nr lud1·~ pulnw 11.1t " 111.I
Dropping of vital capacity <20% of normal lc.1ds to cardiac care, nutriti1111, ,-.1lci11m h11m1~1..1.,..1... .1prtvi" 1' <'
nocturnal hypoventilation. Cardiom yopathy and fmmunizJtiOI\ ,\l\d lll'thopl•d k \".HI' fl'.1bl,• '10 .. ) :\ ,• ,H"C
arrhythmias arc major cardiac manifestations. Children therapies includl• 1•x1111 ""-ippln ~ \1'1 11\~~ .rnt1 " ·l1 n•
with deletion of exons 48 to 53 arc cspeciillly prone to oligonuclcotidc~. Ph.hi· '.\ tri.1t .. l1t1\ ,~ :-lwwn .. 1~n1 t1 ,J11t
cardiac complications. The cause of death is a combination clinical benefits .uhl Ekpl in.l'I\ h,,., t,.,.,, Fl);\ .1pr r••h ·,I.
of respiratory insufficiency and cardiomyopathy. Other although more clink ,,! d.\t.1 1.. r,•,1u1r,·,t 1,1 pr\ln •lb ,·tth .1..:~ .
features include variable degree of intellectual disability
and impaired gastric motility. Myotontc D}'st10(.)/1> 1
Tnx' ·t
Around 10% of female carriers show variable degree It lR the most comnwn mu ..cul.ir dystr1•rhr s'"'" in ... tult~.
of weakness with elevated levels of crcnllnc kinase, calf ThiR dbordt•r trnn,.m lttt'd In .m •\\lto'lum1ll d11nd11.1nt
hypertrophy, myalgias and cramps and Increased risk of monncr, Is r.111st•d hy ~"' 11bnorn1.ll l''r'"ll'illll\ ( - ~ll l ,it
dilated cardiomyopathy. Rarely, the full Duchcnnc trinuclcothlc 1cn;1 1't'pl·.1t.., In tlw l >.\ 11'~ ~l·11c '"'
phenotype is present In girls with complclc Inactivation cluomusonw 19. nw d '""k fonn P''"'''"t" in ,·hlldho,11.t ''1th
of normal X chromosome. myotonlil, fod.11 \\'t'.1l..1ws 'I, d b 1.1l li111li \,·,·.1li.1w"''I. , ,11.11.i. 1~
Semm creatine kinase levels arc highly elevated (>10 (lrldt.•11ct'nt spo\.c-111..t• P''!'i ktlor \7•l1':'I Ul.1r 1.:.11.H..td). m1nr.il
times upper limit of normal), but do not correlate with bnhlno!i!I, c mluninup.,thil'!I (tc ~ tl c ul.u ,1twph)',
severity of the disease or response to treatment. Multiplex hypcrlnsullnlsm, tdC\•nal lltrophy 1md ~ rowth horrH 1111 ~
PCR and the more sensitive multiplex ligation dependent dlsturb,mccs), cMtlh1c .urhythmlit~ 1rnll lliiftur bN
-- Neuromuscular Disorders 1591 -
•
Fig 20 7. (a) Duchenne muscular dystrophy The child presented with progressive gait difficulties and lurching. Examination shows
• · ·muscle weakness, more In the lower
proximal · limbs, calf hypertrophy and positive · Gower sign.
· (bl ~xam1norion Inanother child
shows hypertrophy of deltoid and infraspinatus with wasting of posterior axillary fold muscles (Valley sign)
Table 20.7: Management of Duchenne muscular dystrophy diplegia, clubfoot and gastroparesis. M~otonia is absent in
neonates and infants. There may be a history of decreased
Corticosteroids
fetal movements and polyhydramnios in the mother. EMG
Indication: Children >2 years with static or declining function shows a myopathic pattern and myotonia ('revving engine'
Dose: Prednisolone 0.3-0.75 mg/kg/day sound). Genetic testing is confirmatory.
(initially 0.3-0.5 mg/kg/day, if non-ambulatory) Medications that block sodium channels (procainamide,
Deflazacort, 0.9 mg/kg/day (preferred in children with disopyramide, phenytoin, quinine, mexiletine); tricyclic
excessive weight gain or behavioral problems) antidepressants (clomipramine, imipramine); diuretics
Ensure immunization against pneumococcus, influenza and (acetazolamide, thiazides) and other agents (taurine,
varicella before starting steroids nifedipine, diazepam, carbamazepine, prednisone and
Monitoring albuterol) have been used for treatment, with variable results.
Pulmonary function tests: Every 6 months if non-ambulatory;
Facloscopu/ohumeral Muscular Dystrophy
annually in ambulatory patients .
Echocardiography. Once in 2 yr for <1 O yr of age; annually if The clinical spectrum of this autosomal dominant disorder
>10 years . . ranges from asymptomatic children to wheelchair bound
Serum calcium, phosphate, 25(0H) vitamin Da (biannually) patients. The age at onset is variable. The disease may start
DEXA scan annually with asymmetric facial weakness followed, sequentially,
by scapular fixator, humeral, truncal and lower limb
Physical therapy weakness. Biceps and triceps are typically involved with
Effective stretching and appropriate positioning at ~ari~us sparing of deltoid and forearm muscles resulting in the
joints, assistive devices to prevent contractures, avoid high "Popeye" arm appearance. Lower abdominal muscles are
resistance strength training .. weaker than upper abdominal muscles resulting in Beevor
Surgery: For fixed contractures and spinal deform1t1es sign. Side-to-side asymmetry of muscle weakness is typical
(Fig. 20.8). Other features include high frequency hearing
Other components
loss, Coats disease (retinal telangiectasia, exudation and
Respiratory and cardiac care detachment), atrial arrhythmias and restrictive respiratory
Management of gastrointestinal problems
disease. The diagnosis is confirmed by demonstrating the
Psychosocial management shortening of the macrosatellite repeat D4Z4 which is
Family education and genetic counseling
normally in one allele of 4q35. Treatment is supportive.
Newer therapies h i
c=.. ell therapy p armaco1og ca1 Limb Girdle Muscular Dystrophy
~on skipping, gene therapy, c ti ' read through
approaches (utrophin upregula on, Limb girdle muscular dystrophy is a group of clinically
compounds, myostatin inhibitors) heterogeneous syndromes with autosomal dominant or
recessive inheritance. Most childhood onset limb girdle
g . . till The congenital form may present dystrophies are associated with predominant lower
~tromtestinal mo. ty. d. , hypotonia, facial extremity weakness. Cardiac or other systemic involvement
With respiratory failure, poor fee mg
- 592 ~------~~~~~~--__2E~s~a~on~t~ln~l~Pe~d~la~t~rl~ce!._.--------------~--------~
ll
Fig. 20.8: Facioscapulohumeral dystrophy: (a) Note the facial weakness an(J lnablllfy to completely close the eyes;
(b) Asymmetric scapular winging
is variable. Serum creatine kinase is modestly elevated immune system. Dcrrrnitomyositis is the mo~ t common
but can be high in the sarcoglycanopnthies, dysfcrlino- pediatric inflammatory myopathy, which typically affects
pathy and caveolinopathy. Autosomal recessive limb skin rind muscle but may involve joints, gut, lung, heart
girdle dystrophies have early onset, rapid progress ion nnd nnd other internal orgnns (sec Chapter 22).
higher creatine kinase values. Treatment is symptornntic.
Metabollc Myopathles
Congenital Muscular Dystrophy The metabolic myopnthics arc a group of muscle disorders
These patients usually present nt birth or in first yenr of resulting from foiled energy production relntcd to defects
life. Infants show hypotonia, weakness, arthrogryposis, in glycogen, lipid or mitochondrial metaboli ~ m . The
bulbar dysfunction or respiratory insufficiency. Weakness symptoms arise due to a mismn tch between the rate of 1
is static or slowly progressive. Diagnosis is supported by ATP utiliz<1lion and the cnpncity of muscle metabolic
dystrophic myopathic features on muscle biopsy, elevated pathways to regenerate ATI'. Affected children ilnd adults
creatine kinase levels and exclusion of common present with exercise intoleran ce, wcnkness and
myopathies of newborn. myoglobinuritt; newborns nnd infants present with serere
~ultis~stem disorders. Most metabolic myopatllics ha\'e
Suggested Reading mterm1ttent rnther thnn stntic findings. Sunw children
• Bimkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell /\, present with progressive proxim<1l musc le \n'akness
Brumbaugh D, et al. Diagnosis and management of Duchen nc mimicking" dystrophy or an inflammatory m:;npathy.
mu scula r dystrophy, part 1: diagnosis, 11nd ncuromuRc1tl;ir,
rehabilitation, endocrine, and gastrointes tinal ;ind nutritional In patients with glycolytic or glycogenolyt 'c defects,
management. lancet Ncurol. 2018 Mar;17(3):251-67. symptoms arc induced by either brief isomet ric exercise.
• Bimkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Colvin such ?s lifting heavy weights, or by less intense. b~I
MK, et al. Diagnosis and management of Duchcnnc muscular s usta rned dynamic exercise. In di sorders of lipid
dys trophy, part 3: primary care, emergency management,
metn~olism, the.abnormalities nrc induced by prolon~ed
psychosocial care, and transitions of care across the lifespan. Lancet
Neurol. 2018 Feb 1; pii: 51474-4422(18)30026-7. e~ercisc and fastmg. lnvcstignlions include scrum cre.1tu1e
• Bonne man CG, et al. Diagnostic approach to the congenll11 l kmnsc nnd amrnonia, urine myoglobulin, tandem niJSS
muscular dystrophics. Neuromuscul Disord. 2014;24(4),289-::n l. spectroscop7, gn.s chromntography mnss spcc troniet~~·
• Gloss D, Moxley RT, Ashwal S, Oskoui M. Practice guidcllnc updntc clcctrophys1olngtcnl s tudies, forearm ischcmia cxerc1~e
summary: Corticosteroid treatment of Duche nne muscle test, muscle biopsy nnd moleculnr studies.
dystrophy. Neurol 2016;86:465- 72.
• Patient education leaflets is available at htlp://nilm!l.cd11/allm!i/ Suggested Reading
departments/ pediatrics/ ped_neu ro/ pa tlented LI .him
• Thornton CA, Myotonic dystrophy. Ncurol. Clln. 2014;32(3):705-719. • !3crnrdo /\, Dit\fourn S, 1-llrnno M. A dia~noslic ,1 Jgorilhll\~~l:
mctnbollc myopa thic~. Curr Ncurnl nc uroscknce Rl'I'· 2
Inflammatory Myopathles Mar;10(2):118- 26. .
• l.illckl!I' Jll, Kl'l1 YS, Ron cnroli P, Sharma R, l~olll•rls M. f1kt.1 l~~~
The inflammatory rnyopathies are a diverse group of mynpnlhil'!I: n pr.1cllc11I nppronch. Prnctlcal Nl•urology. 2017
disorders in which muscle appears to be injured by the H; prnclnc~ urol·2017-001708 .
Chapter
21
Childhood Malignancies
Rachna Seth
rI
Tumor
Table 21.2: Predominant pediatric malignant tumors by age and slle
Less than 1 year 1-12 years 12.-21 yflart1
I
Leukemia Congenital leukemia Acute lymphoblastlc leukemia (ALL) Aouta lymphoblHBllo l~tJk~mlrt
Acute myeloid leukemia (AML)
Juvenile myelomonocytic JMML (<3 years) Acute my~lold leukqml11
leukemia (JMML) Chronic myeloid leukemia (age :>3 years)
CNS Medulloblastoma Medulloblastoma Cerebtlllar flBlrocytomo
Ependymoma Ependymoma Astrocytomo
Astrocytoma, glioma Astrocytoma, glioma Cranlophnrynoloma
Choroid plexus papilloma Choroid plexus papilloma (<3 years) Medulloblastom11
II Lymphoma Rare
Craniopharyngioma (older child)
Cerebellar astrocytoma (older child)
Non-Hodgkin lymphoma
Hodgkin lymphoma
Hodgkin lymphomo
Non·Hod9kln lymphoma
Chest Neuroblastoma Neuroblastoma (common up to 4 years) Lymphoma
Teratoma Lymphoma (commoner In :>4 years) Ewing sarcoma
Teratoma
Rhabdomyosarcoma
Head and Neck Retinoblastoma Retinoblastoma (<5 years) Lymphoma
Neuroblastoma Neuroblastoma (younger child) Soft tissue oarcoma
Rhabdomyosarcoma Lymphoma (>4 years)
Rhabdomyosarcoma
Abdomen Neuroblastoma Neuroblastoma (younger child) Lymphoma
Hepatoblastoma Wilms tumor (younger child) Liver carcinoma
Wilms tumor (>6 months) Lymphoma (older child) Soft tissue sarcoma
Hepatoblastoma Dysgorminoma
Yolk sac tumor Rhabdomyosarcoma
Genitourinary Teratoma Rhabdomyosarcoma Teratocarclnoma
Yolk sac tumor Teratoma
Embryonal carcinoma
Extremity Fibrosarcoma Fibrosarcoma Osteosarcoma
Rhabdomyosarcoma Ewing sarcoma
Ewing sarcoma Soft tissue sarcoma
Multlsystem Langerhans cell Langerhans cell histiocytosis
histiocytosis
depending on their natural history. Acute lymphoblastic Acute Myelold Leukemia (AML)
leukemia (ALL) and acute myeloid leukemia (AML) are Acute myeloid leukemia (AML) also termed as acute non·
common; a small proportion has chronic myeloid leukemia lymphoblastic leukemia, the second most common type
(CML) and juvenile myelomonocytic leukemia (JMML). of leukemia in children, accounts for 15-20% of leukemia
in children. AML is much more complex and rcslstnnt
Acute Lymphoblastlc Leukemia (ALL)
disease than ALL and results from clonal proliferation of
ALL is the most common childhood malignancy accounting hematopoeitic precursors of myeloid, crythrold and
for one-fourth of all childhood cancers and three-fourths of megakaryocytic lineage. Intensive myclosupprcssivc
all newly diagnosed patients with acute leukem~a. Its induction and post-remission therapy result In Jong-tcrrn
incidence is approximately 3-4 cases per 100,000 ch1l~ren survival in 40-50% patients.
below 15 years of age. Boys have higher rates .than gir~s,
especially in adolescents with T-cell ALL. There 1s a peak m Etlopathogenesls
incidence of childhood ALL between2 and 5 years due to ALL
The etiology of acute leukemia Is unknown In the mnjorllY·
associated with a pre-B lineage (common ALL). Significant
Several genetic syndr?mes arc nssoclntcd with on
progress in treatment of ALL in last two decad~ has lead to
increased risk of leukemrn (Table 21.3).
cure rates of over 80% in most developed countries.
L--------------------------------C~hi~ld~h~o~o~d~M~a~l~lg~n!an~c~l~es~--------------------~ I 595 1111111
r=-::-::~====~--:--lTi~abbJl~e~2~1]~~:r.G~e;n;eti~c~a~n~d~e;nv~~lro;n~m~e:n~ta~~~-ri~s~~~fa~ci~o~~-.f~or~c~h~il~dh~o~od~·~1e~u~k-e~
m la--~---....~~~~~
Environmental -- ' ~ '
·· · ·-·
Down syndrome
Ionizing radiation
Fanconi anemia
Alkylating agents: Cyclophosphamide, ifosfamide, carboplatln, procarbazlne
, Shwachman-Diamond syndrome
Epipodophyllotoxins: Etoposide, tenoposlde
Bloom syndrome
Nitrosourea: Nitrogen mustard
·Ataxia telangiectasla Benzene
Olamond-Blackfan anemia
1
Kostmann syndrome
1Li-Fraumeni syndrome
1
Severe combined immune deficiency
Paroxysmal nocturnal hemoglobinuria
, Neurofibromatosis type I
Fig. 21.2: (a) Bone marrow from a child with acute lymphoblastic leukemia shows red uced norm a l marrow elem ents which ore
replaced by lymphoblasts. The neoplastic lymphoblasts are slightly larger than lymphocytes and have round or convoluted nuclei,
fine chromatin, often with a smudged appearance, Inconspicuous nucleoli and scant baso philic cytoplasm. (b) Peripheral smear
of a 6-year-old child diagnosed with acute myelold leukemia (AML-M2Jshowing a myeloblost containing an Auer rod (pink-colored
aggregated lysosome)
r~.~. _. ,_· Table~~ .4: Frefl~h-American-Britis~ (F~) classification of acute lympho~!!lst!~ leukemia_
Cyto/ogig features L 1 (Bo-85%) L2 (15%) L3 (1-2%}
Cell size Small cells predominate; homogenous Large; heterogeneous Large; homogenous
'Amount of cytoplasm Scanty Moderately abundant Moderately abundant
Nucleoli Small, · inconspicuous One or more, often large One or more, prominent
Nuclear shape Regular, occasional clefts Irregular clefts, indentation Regular, oval to round
• - .... ~·- ,. .. -· 1
f Ta~le 21.6: Classification of acute myeloid leukemia (AML} Clinical Features
French-American-British (FAB) classification The duration of symptoms in a patient with ALL varies
MO Minimal differentiation from days to weeks and in some cases few months. The
clinical features are attributed to bone marrow infiltration
M1 Myeloblastic leukemia without maturation
with leukemic cells (bone marrow failure) and
M2 Myeloblastic leukemia with maturation extramedullary involvement, and include pallor and
M3 Promyelocytic leukemia fatigue, petechiae, purpura or bleeding, and infections.
M4 Myelomonocytic leukemia Lymphadenopathy, hepatomegaly and splenomegaly are
M5 Monocytic leukemia present in more than 60% (Fig. 21.3a). Bone or joint pain
M6 Erythroleukemia and tenderness may occur due to involvement of
periosteum of bones or joints; skin rash/ eruption may also
M7 Megakaryocytic leukemia
occur. Infants and young children may present with a limp
or refusal to walk. Tachypnea and respiratory distress may
Acute Myeloid Leukemia be present secondary to severe anemia leading to
The classification is summarized in Tables 21.6 and 21.7. congestive heart failure or secondary to the presence of
Myeloblast containing an Auer rod is shown in Fig. 21.2b. mediastinal mass leading to tracheal compression
- .t
-· T!ible 21.1: Gerieti? abnormalities in-AML ··'"'""':. - · ~-- · --- --·~ --·· .~~- •· - .
. • • •"I
Deletion Sq
Monosomy 7 .
~ .
r' <35
l~. .. <35
Childhood Malignancies 1597 -
Fig. 21.3: (a) AA 8-year-old child presented with acute lymphoblastic leukemia, prolonged fever and generalized lymphadenopathy;
(b) A ~-year-old child~ acute myelold leukemia showing bilateral subconjunctival bleeds. (c) A 9-year-old child with acute
myelo1d leukemia showing gum hypertrophy; (d) A 10-year-old girl with acute myelold leukemia presenting with proptosls (chloroma
orbit)
(superior mediastinal syndrome). A large mediastinal thrombocytopenic purpura (ITP), aplastic anemia and
mass may cause superior vena cava syndrome with facial viral infections (e.g., cytomegalovirus) that might result
edema and plethora, throbbing headache, conjunctiva in leukemoid reactions and pancytopenia. ITP is the most
congestion and dilated neck veins. common cause of acute onset petechiae and purpura in
Patients with high tumor burden may present with very children. There is no evidence of anemia and have normal
high total white cell (TLC) count (hyperleukocytosis, TLC TLC and differential count. Bone marrow smear reveals
>100 OOO/mm3 ) or tumor lysis syndrome. normal hematopoiesis and normal or increased number
A few patients (5-10%) have central nervous system of megakaryocytes. Aplastic anemia may present with
involvement at diagnosis; they present with cranial nerve pancytopenia, or juvenile rheumatoid arthritis with fever,
palsies, seizures and occasionally raised intracranial joint symptoms (limp, arthralgia or arthritis), pallor,
pressure (headache, vomiting, irritability, papilledema). splenomegaly and leukocytosis. ALL should be
The diagnosis of CNS leukemia is made on examination distinguished from other malignancies (neuroblastoma,
of the cerebrospinal fluid. Overt testicular leukemia is seen non-Hodgkin lymphoma, rhabdomyosarcoma, Ewing
in -1 % boys, when it presents with firm, painless, sarcoma and retinoblastoma) that present with bone
unilateral or bilateral swelling of the testes; the diagnosis marrow involvement.
is confirmed on biopsy. Rare sites of extramedullary
Laboratory Features and Diagnosis
involvement include heart, lungs, kidneys, ovaries, skin,
eye or the gastrointestinal tract. Clinical presentation, peripheral blood counts and
The clinical presentation of AML is similar to ALL but morphology are indicative of the diagnosis of ALL
more likely to have high TLC and incidence of infections (Table 21.8). Children may present with pancytopenia or
(Fig. 21.3b). Unlike ALL, lymphadenopathy and massive
Tabie 21.S: Evaluation of a child with suspect~d ·leukemia
hepatosplenomegaly is not very common. However, infants
and toddlers with M4 and MS AML subtypes have more • History and physical examination
organomegaly, high leukocyte counts and CNS disease at • Complete blood count and differential count
diagnosis. Gwn hypertrophy a common feature of the M4 • Peripheral smear examination (cell morphology), leukocyte
subtype (Fig. 21.3c). Disseminated intravascular platelet count, immune phenotype
coagulation may occur with any subgroup, but is common • Chest X-ray (include lateral view, if mediastinal mass is present)
in acute promyelocytic leukemia (M3). Chloromas are • Blood electrolytes, urea, creatinine, uric acid, lactate
localized collections of leukemic cells that which may occur dehydrogenase, calcium, phosphate, bilirubin, and
at any site including CNS, neck, bones (typically orbit) and oxaloacetate and pyruvate transaminases
skin (Fig. 21.3d). Patients with high TLC may present with • Prothrombin time, coagulation profile
signs of leukostasis such as pulmonary infiltrates causing • Bone marrow aspirate: Morphology, immunophenotype,
respiratory distress or stroke. Central nervous system cytogenetics, FISH/PCR for specific translocations
involvement may occur in up to 15% patients. • Bone marrow biopsy
• Serology: HIV antibody, hepatitis B surface antigen and
Differential Diagnosis antibody, hepatitis C antibody
The clinical profile of ALL may mimic infectious • CSF cytology (give first dose of methotrexate with diagnostic
mononucleosis, acute infectious lymphocytosis, idiopathic tap)
- 598 I
hyperleukocytosis. The diagnosis Is confirmed by lnduoffon moropy
peripheral smear examination and bone marrow asplrnlc The goal of this phuflC! fg to er;tclk;; f1• lf•t1k<:mla ~ud1 th-'t
and biopsy. It is necessary to perform an aspirate M well nt end of thl1:1 phm1c ttwn· Me ~5'Y,, lcuhm1lc bla~f~ in H~
as biopsy at time of initial diagnosis. Higher leukocyte bone mnrrow. fnduction therapy with iJ rer,lm1f1um1birrlt1'1.
(TLC) counts are more common with T cell A LL. The bone vlncrlstlnc and precl11ifwne adrrdnlc:ten:d f 11r 4 ·111·1·1'~
marrow where >25% of bone marrow cells nre leukemic induces rcmif.mlon in H0- 95% p11tinlt.'i. Cum·nt indu<.tlon
lymphoblasts is diagnostic for ALL (20% in case of AML). rcglmena thnt combine vinc:ri 11tirw, pr~d11ie;ol<J~e, f,..
While morphology of the leukemic blasts can give aHparngin11Hc and an anthrncycHnc re~ult in rnmi~A1<111 iri
important clues to the diagnosis, it needs to be confirmed 95-98% by 4-6 wcckH. f';iticntll who ac.hh~vc rapid early
by immunophenotyping of the bone marrow. Immuno- rcmiasion (<5'.Y,, bla1:1ts in m ll rtO 'N) by day 7 o r 14 <1f
phenotype differentiates the cellular lineages of ALL into induction have a better pror,.nooi~ than t}low tt-sp<Jndl'f~.
pre-B, T cell and mature B cell. This distinction is important Failure to achieve this al end of induction Is a~wcfated
as there are therapeutic implications of the cellular origin with high-risk of relapse.
of ALL. The diagnosis for AML is also ascertained by
CNS Prevenl/ve Therapy
peripheral smear and bone marrow examination, with
determination of morphologic, cytochemical, immuno- Most children with leukemia have s ubclinica l C1'S
phenotypic and genetic characteristics of blast cells involvement at diagnosis, which might act a<J a ganctuary
(Table 21.7). where blasts are protected because of the blood-brain
barrier. CNS prophylaxis has enabled incrcagcd r,u rvival
Evaluation of CSF for blasts to determine CNS
rates in leukemia. Given the concern of long-term
involvement is important for staging. The spinal tap is
neurotoxicity and risk of brain tumors folluwin~ standard
performed ideally with platelet count -100000/mm3 .
cranial irradiation, experts recommend lowe r do-,e
Children with CNS leukemia require more intensive
irradiation combined with intrathccal adminis trati(Jn of
therapy. Occasionally, the diagnosis of AML is preceded methotrexnte. Alternative regim ens include the use of
by a prolonged preleukemic phase las ting several weeks triple intrathecal therapy consisting of m e thotrcxate,
or months, characterized by lack of one of the normal hydrocortisone and cytarabinc without cranial irradiatfon
blood cell lineages, with refractory anemia, moderate or high dose systemic chemotherapy. Others propose that
neutropenia or thrombocytopenia. The condition is irradiation be limited to patients with high risk fc·a tu n..-s
referred to as a myelodysplastic syndrome; some patients at diagnosis, including T cel l ALL with leukocyte counts
show hypoplastic bone marrow that develops later into >1000 OOO/mm3, Philadelphia chromosome positive and
acute leukemia. presence of CNS leukemia.
and presence of minimal residual disease at end of show better outcomes than AML ln lhosc wllh<ni t tr16Qmy
induction by PCR assay or by flow cytometry (Table 21.9). 21. Children with trisomy 2'1 nro also ill hlHh~r rl!!.k ft>r
-15-20% patients with ALL relapse, most commonly ALL. However, these patients do not show ii pr1-tl~L•l<Dml.c
in the bone marrow followed by CNS and testis. The phase and their outcome is inforior ("o lhqso wilhtmt Oown
prognosis for patients who relapse depends on the site syndrome and ALL.
and time of relapse. Early bone marrow relapse before
completing maintenance therapy has the worst prognosis; Suggested Reading
late relapses after cessation of maintenance therapy show • Arora RS, Arora Il. Acute leukemia In chll4r11•l; A rvvlttw uf fjw
better (30-40%) survival. Relapse at extramedullary sites, current Indian data. South Asian I Cancer, :Wlf1; 1.i(3):l 51)... Jf)IJ,
particularly testis, is more favorable in terms of survival. • Seth R, Singh A. Leukemias in children, lndlim 1Pi1dlalr ?J)I ~; 82(?);
R
Late isolated CNS relapse (>18 months) can be effectively 817-24.
cured with cranial irradiation and systemic chemotherapy. • Taga T, Tomlzawa D, Takahashi I l, Adachi 8. A(;ul(I myt lnJd
leukemia in children: Current i;tatus 11nd fµture d lrn.:lhms, 1'~1llAtr
Therapy for relapse is more aggressive than first line Int 2016; 58: 71-80.
therapy. • Pui CH, Carroll WL, Mcshlnchl S, Arc11cl It Olol n ~y, rhk
Adverse prognostic factors in AML include: Older age, stratification and therapy of pedlt1lric acut~ JeukPmlas: 1111 upd a~,
obesity, MO and M7 subtype, and CNS disease at J Clin Oncol 2011; 29:551-65.
diagnosis. Lack of minimal residual disease, M3 subtype, • Pui CH, Y11ng JJ, Hunger SP, PiL~ters R, Schrnppc M, Ulond l A, tt
AML associated with Down syndrome and presence of al. Childhood acute lymphoblastlc leukemia: Prngr•t6ti thmuy,h
collaboration. J Clin Oncol. 2015;33:2938- 4fl.
favorable cytogenetics [Inv16, t(8;21), t(15;17)] are
associated with favorable outcome.
CHRONIC MVELOID LEUl<EMIA
Late Effects of Treatment Chronic leukemias constitute 3% of Jcukc min i; in
Long-term effects of treatment are of concern. Patients who childhood. Chronic myeloid leukemia (CM L) iR a clonal
have received cranial irradiation at a young age are at risk disorder that originates in a pluripolent hematopoietic
for cognitive and intellectual impairment and development stem cell and is characterized by myeloid hyperpl asia of
of CNS neoplasms. There is a risk of secondary AML after the bone marrow, extra med ullary hc mal o poi1·sifl,
intensive use of epipodophyllotoxins (etoposide, elevation of white blood cell count (with appeara nce· of
teniposide). Endocrine dysfunction leads to short stature, the complete range of granulocyte precursorn in the
obesity, precocious puberty, osteoporosis, thyroid peripheral blood) . CML bears a specific cytogen1~ tic
dysfunction and growth hormone deficiency. Patients marker that is known as the Philadelphia (J' h)
with prior therapy with an anthracycline are at risk of chromosome. Ionizing radiation is implicated in the
cardiac toxicity. pathogenesis of CML. Two main forms of well d iffcr,·n·
tiated myelogenous leukemia are recognized .
Down Syndrome and Acute Leukemia
Adult CML: TI1e condition is clinically and hematologk;,illy
Children with Down syndrome (trisomy 21) have a 15-20 comparable to the adult form of chronic myclogcnnus
fold higher risk of acute leukemia, compared to the general leukemia and occurs in children above the age of 4 years
population with a cumulative risk of -2.1%. The ratio of (Fig. 21.Sa).
ALL to AML in Down syndrome is similar to that in other
children. One-half to two-thirds patients of acute leukemia Juvenile CML: This form presents in infancy and 1· 1rly
in children with Down syndrome are ALL, the exception childhood, usually below the age of 4 years, and h'1s a
being the first 3 years of life when AML predominates more rapid course (Fig. 21.5b).
and exhibits a distinctive biology. Approximately 10%
children with Down syndrome develop a preleukemic Adult Variety of CML
clone, transient myeloproliferative disorder with somatic Though the adult variety of CML is a common leuk.·1nia
mutations in hematopoeitic transcription factor GATAl. in adults, it is rare in children accounting for 3-5% c:i-;cs.
These children present with high leukocyte count, CML patients show a triphasic course: The usual phoise at
circulating blasts in peripheral blood, hepatospleno- diagnosis (- 85% patients) is the chronic phase, which may
megaly, effusions, anemia and thrombocytopenia in the progress to the accelerated phase and blast crisis
neonatal period, which resolves by 3 months. About 20% resembling acute leukemia in which myeloid or lymphoid
patients with the transient myeloproliferative disorder blasts proliferate in an uncontrolled manner.
develop AML. AML in children with Down syndrome Children present in the chronic phase with fatigue,
generally develops before 5 years of age, has low leukocyte malaise, weight loss, excessive sweating, abdominal
count and does not have CNS involvement; two-thirds fullness, and bleeding due to platelet dysfunctioni
show acute megakaryocytic leukemia (FAB M7). Since splenomegaly is usually massive. Symptoms of leukostnsis
blast cells in these patients have high sensitivity to such as headache, dizziness and visual disturbances mnY
medications, they require less intense chemotherapy and occur rarely. Symptoms in the accelerated phase or blnst
Childhood Mallgnancles
I &01 -
count shows all forms of myeloid cells from promydocytes,
myclocytcs and mctamyelcxytes to polymorphonud€'ar
,, .. leukocytes; ba5ophilia is common. Genetic testing for the
,:. ~ ,"/· ..l
) ...t' , ' ,• •
l/ Philadelphia (Ph) chromosome in conjunction with
marrow morphology allows confirmation of the diagna;is.
..f ,
. .. ..__ . \~
Treatment
The aim of treatment is to control increasing white cell
counts. First and second-generation oral tyrosine kina:,e
inhibitors (TKI) arc the treatment of choice. !viajorit-f of
patients achieve complete hematologic and cytngenetk
response following imatinib therapy and the rate of
progression to accelerated or blast crisis is reduced. The
I
starting dose of imatinib is 340 mg/ m 2 I day. Bone marrow
cytogenetics is monitored every 6 months until a romplete
cytogenetic response is obtained. Survival after
development of accelerated phase is usually less than a
year and after blast transformation only a fev.- months_
Allogeneic stem cell transplantation is recommended for
patients who do not respond to TIU.
donw- l$ r~ :-en\. i;:unw:J (rn111 11 IOil· fold h1ercaaed ri!:lk ln monozygotJc twins
compun.'d with dl:t.ygolk twlnfl. J.!pld.emiol.ogic studies
ht\Vl! l'llltW,l'rilcd ll11kr1 between 1:-lo~gkm lymphoma ~nd
7
vlr"I ll111c11ricr1 llk1! Ep1-1 lcl11-IJL1rr virus (EBV). EBV viral
DNA Cilll \Jc (ound In I ludgkln-Hecd-Sternberg cells,
sugp,cttllng nwnodo111.1I prnli~ernll?n ?f the neoplastic
clone follow Ing Infccllon. EJJV infection is commonly seen
• Raul L' Cht\'l\k m~'\'\,,lct \<'\1\..\'ml:I \" l"\1lkh~n: A \.wlrt' 1·,~vl1•w. In ymmri children with mixed ccllularity disease. Immune
Clin C~nC\'t hwt'$1\~ ) .. ~l'\U;~~C\~-i\ , defldc1~t:y (co11gcnltal/nc:quire<l) and autoimmune
• &\ITT\'P ~L Ec\..af\it l_ T.\\11•t Ji, ~l\\1111 l:, M111\1\~1•m1•nt nl' dmmlc
condlthmH (rheumatoid arlhrili1:1, SLE, sarcoidosis, ITP) are
m~~ll.'i-l k\\\..t'mi~ \" chi\,ihC\\"-l. C\m \\1•111;1111\ M:1Hl\ \~"I' :Hl\2;
~\l~~·t 1\SSodnlcd with lncrcmicd risk of Hodgkin lymphoma.
• Tani?awa .-\, Qrtima\ ""'""Se"wnl for \'''\\.\Irk d1ri1nk my1•l1lhl
l~\U:: mi<\ .. l't'diatr lnt 20\t\; ~'\: r;·1-~. Pathology
Lymph nodes nrc the most common tissue on which the
LYMPHOMA dlni;nosh! of l lm.lgkin lymphoma is made. However, liver,
Lrmphomas are the third most comml)n m1\li~1\lmcy, spleen, bone marrow or lung may provide the material
compri$ln~ 10-15% l'f childhood ~""l't'l'S. Ahnul 60% m·c
f01· histological examination. It is necessary to obtain the
non-Hodgkinlymrhomaand40%are Hod~k\n lymphom,\ entire node by excision biopsy for proper examination.
tTable 21 . 11), Fine 1wedlc <lspiralion biopsy and frozen section material
nrc not optimal for histology.
HODGKIN LYMPHOMA
The Wl 10 classification of Hodgkin lymphoma
recognizes lwo subtypes: Nodular lymphocytic predomi-
Hodgkin lymphoma is a lymphmetkulnr 1\l•oplnsm nant Hodgkin lymphoma (NLPHL) and classical Hodgkin
primarily of B cell \Uw,1ge thilt itw0\w~ lymph nodes nnd lymphom.l. NLPI IL subtype is characterized by large cei:s
the lymrhatic system . The incidence r.,n~l'S from !'-7 I with mullilobed nuclei referred to as popcorn cells. These
100,000 population; the conditi0n is unrtmHnnn lwlow lhc pnlicnts arc generally asymptomatic and present with
age of 5 years and exhibits thrt'l' di!•tind forms \n localized nonbulky mcdiastinal disease. The hallmark of
developing countries: The childhoNi iorm (ymm~cr thnn classic Hodgkin lymphoma is the Reed-Sternberg (RS) cdl,
1-t years),,, young <ldult form (15-t-t ye1us) ''"d olckr ndult n binucleated or mullinuclcated giant cell with bilobrd
form (SS-7-l years). There is n m.llt' prt•pcmdcrnn~·c (10:1) nucleus and two large nucleoli, giving an owl eye
in children affected below 7 yl'ars of n~c, with l'qunl sex nppenr:-incl! to the cells. There are four varieties of Hodgkin
distribution beyond l~ ye.us of a gt'. The Ynst mnjtwity (80- disense, characterized by the number of RS cells,
90%) achieYe disease remission with m\\ltingent characteristics of inflammatory milieu and presence or
chemotherapy with or without r:-idiotherJpy. nbscncc of fibrosis (Table 21.12). Nodular sclerosing is the
. .
Table 21.11: Clinical features of Hodgkin and non-Hodgkin lymphoma
Clinical feature Hodgkin lymphoma Non-Hodgkin lymphoma
Nodal spread Continuous Discontinuous
Localized Yes Rare
Extranodal disease Rare Common
Central nervous system disease Rare Common
Bone marrow involved Rare Common
Class B symptoms Common Uncommon
Abdominal disease Uncommon Common
Subtype based therapy Not Important Crucial
Cure rates 85-90% 70-80%
Childhood Mnllgnnnoln•
most common type in developed countries, wherens in lymphocy h' d1~plollo11), h11lk y 1111•1f1,1 tt tln 11 I rl ltw.1'111,
developing countries including India, the mixed cellularity extensive splt•11lc lrw11lv1•1111·11t .111d mon• th.rn 'i 11od.il l'ljt,..,
type accounts for -60% cases. On immunophenotyping, in stngc Ill. Bmw lnvol v1•11w11t hy 111.,.,lc,11 I II. 11111y c.111·1•
the classic subtypes are positive for CD15 and CD30 nnd pain. BorH~ rnnrrow l11volv1•m .. nt r.tr•·ly fl! /W IH lu
may be positive for CD20, whereas NLPHL is negative cytopcnins nnd hns li1•1•11 ns1wd,11t•d with 11 v .irkty of
for CD15 and CD30 but positive for CD20 and CD45. parnneoplnstic syndrom1 :"1. 1
a
~ • I .
Fig 2l 6 . ( l This
10-year-old boy presented with fever and significant bllatorot c orvlc al lyrnpt1oc.Jonopotrw. Lympt1 nrxJ0 t)lrmw
sh~wed f~a~ures of Hodgkin lymphoma; (bl A 10-year·old boy with lover, slgnlrtcont rtoht c orvtcot tyrnpllac.Jonopothy woi <Jl<J~rlf)~'"J
as Burkitt lymphoma; (c) Chest X-ray of a 7.year·old boy with medtasllnat mass and tort -slcJocJ plourot otlu11lon. Ho wm dlo<Jno .'XJ
as T lymphoblastlc lymphoma on lymph node biopsy
- so4 I ~--~--~~~~~~--~--_!:E~s~s~e~n~ti~al~~P~ed~i~a~tr~lc~s!._.__.------~~~~~~~~~~-:------..........
. linun· ation of radiation-associated adverse
Tobie 21 , 131 Diagnostic evaluation tor children with ~odgkin approach is e · J k l
effects like myocardial dysfu~ct1on, muscu os e etal
lymphoma owth deficits and second malignancy. . .
. Physical oxamlna11on; measure size and number of lymph gr t for patients with favorable clin1caJ
nodes . r (localized node involvement: Stage r, II, JIIA;
Treatmen
Complete blood counts, ESR, CAP. liver and renal functions, presenta IOfnB symptoms·/ no evidence of bulky disease)
alkptlne phospha1ase, LOH
absence o I I
· f 2-4 cycles of chemotherapy (ABVD ot 1ers) and
consists o f bl 1· · I
Biopsy of lymph node or involved extranodal site low dose involved field radiation. Un a~ora e ~ mica
Chest X-ray posteroanterior and lateral views; measure . (B symptoms· bulky mediastmal/penpheral
presen ta t10n ' . f d'
medlastlnal mass thoracic cavity ratio lymphadenopathy; extranodal extension. o 1sease;
CT scan: Neck, chest and abdomen advanced disease: Stage IIJB-IV) are treated with 4-6 cycles
r -
- . .. - --· - - ..... __
Table 21.14: Modified Ann Arbor staging for Hodgkin lymphoma
Staoo Involvement
I Slngle lymph node region (I) or one extra lymphatic site/organ (le) by direct extension
•II Two or more lymph node regions on the same side of diaphragm (II), or one or more lymph node regions on sar' ..
side of diaphragm plus local extralymphatic extension (llE)
. Ill Lymph node regions on both sides of the diaphragm (111), which may be accompanied by local extralympha .~
extension (Ille)
1111 Abdomen disease is limited to the upper abdomen: Spleen or its hilar nodes, celiac nodes, porta hepatis nodr. ~
1112 Abdomen disease Includes paraortic, mesenteric and iliac nodes, with or without disease in upper abdomen
IV Diffuse Involvement of one/more extralymphatic organ/sites with or without associated lymph node involvement
A No B symptoms
'B Presence of at least one of the following:
Unexplained weight loss >10% baseline during 6 months before staging
Recurrent unexplained fever >38°C
Recurrent night sweats
x Bulky tumor
X Bulky tumor Is either a single mass of tumor tissue exceeding 10 cm in largest diameter, or a mediastinal mass extending one-third of the
m1uclmum transverse intrathoraclc diameter measured to the inside of the ribs on a standard posteroanterior chest radiograph
E IHlon Localized extranodal extension of Hodgkin lymphoma from a contiguous/nearby nodal site
Childhood Mnllgnnnclos I sos -
• Radma S, Das RR. Puri K. Sinsh r, Clinic,,\ Pt'\'fll~ i\thl ddicicncy nnd DNA rcpnlr deficiency syndromes
~:her~py ~~in chilJn•n \\ith Ho...\_~\...h\ lymp h\11\\;\ ''t I\ (Wi~kott-Aldrkh syndrome, X-llnkcd lymphoprolifcrntivc
~- ca..-e '-"'ent:\?.. J Clin Di.JS Rt.'S ::0 t::; 9:SC~5--.~>l).
ctisurdct·~ nnd ntnxin t('lnnglcctnsin) , ncquircd
immunoddlclcncy syndrome nnd orgnn trans plantation
NON-HODGKIN LYMPHOMA
(post-trnnsplant lymphoprolifc.•rnllvc discnse). Infection
Non-Hodgkin lymphoma (NHL) 1.."0mprises a lwt~rn with mnlntfa nnd ED virus arc considered risk factors for
geneous group of neopl,1sms that most romm1.mlY tlCCur Burkitt lymphomn.
during the second decade. To~thff \\itil Hodgkin ~iisl'nse,
N""HL comprises the third most common childhood
I
Pathology
malignancy. The major his tological types of NHL arc 13urkitt/Burkitt-
likc lymphoma (BL), lymphoblastic lymphoma (LL),
Epidemiology diffusc llll'gc U cell lymphomn (DLBL) nnd nnaplastic large
The relative frequency and incidence of NHL show cell lymphoma (ALCL) (T<lblc 2·us).
geographic \-a.riations.. There is male p1~ponder•mt~. with
male to female ratio of 3:1 in duldren <15-w,u-old. NHL is Cllnlcal Features
uncommon before 3 rears of ..ige.. Age-s~1t'\:ifk h~nds of NHL in children hns distinct clinical and behavior
incidence of t\.Tfil may correlate \\ith histologk subtypt.'. properties when compnrcd to adults. Lymphomas in
Burkitt and Burkitt-like lymphomas occur in childrl'n adults are commonly low or intermediate grade and are
between 5 and 15 years, wllile the incidence oflymphobklstic dominantly nodal, have variable growth fraction with
lymphoma is constant aero..-;:; all age groups. Diffuse 1'1rge B poor long·ll'rm outcome. NHI. in children is high grade,
cell l)mphoma (DLBCL) is a disease of older .1doles1..~nts. In e:xtrnnmfal with high growth fraction nnd good outcome.
equatorial Africa, 50°a of all cancen; are lymphom'1s (chiefly Children usually present with extrnnodal disease
Burkitt l)mphoma). In United States and Europe, one-third involving the mcdi'1stinum, '1hdomen, or head and neck
of childhood NHL is lyrnphoblastic, one-half '1re sm'1ll region (Fig. 21.6b). lntrathoracic NHL, most often T-cell,
nondea,·ed cell lymphomas (Burkitt, non-Burkitt or Burkitt- m'1)' have fo'1turcs of superior mcdiastinal or superior
like) and the rest are large cell lymphom'1s. In Indi'1, vcna c'1val syndrome. There may be associated pleural or
lymphoblastic lymphoma is more conunon. pericardial effusion (Fig. 2·1.6c). Cervicnl ndenopathy,
Lymphoblastic lymphomas are T cell deri\ ed, while '1bdominal pain, ascites, pnlpnble abdominal mass,
undifferentiated lymphomas (Burkitt, non-Burkitt) '1re intestinal obstruction or intussusception, cranial nerve
B cell derived. NHL may follow previous chemother'1p)' p<11sy, boncorj'1W swelling, and cytopcnias due to marrow
for Hodgkin disease, or be associated with immuno- involvement nre other fcnt11res.
r --- _...... -
f;... Table 21.15: Types of non-Hodgkin lymphoma (NHL)
' Type Immune type Features Translocatlon Remarks
Burkitt, Burkitt- Mature B cell (surface Intra-abdominal, head, t(B:14)(q24;q32) India: sporadic form is common
. like lymphoma lgG ±lgM) neck; jaw (Waldeyer ring) t(2;8)(p11 ;q24) and with abdominal presen-
50% of NHL CD10, 19,20;kappa Less common: CNS, testes, t(B:22)(q23;q23) tation
and lambda marrow Africa: Endemic form common
with jaw mass
Diffuse large B Mature B cell Nodal, abdomen, bone t(B: 14)(q24;q32) 10-20% of NHL; often localized
cell lymphoma CD 19, 20, 22, 38, 79a Less common: CNS, t(2;17)(p11 ;q24) 20% present as primary
(DLBCL) marrow, mediastinum mediastlnal disease; poor
10-20% of NHL prognosis
Lymphomatous Pre T cell (-70%) Mediastinal, bone t(1 ;14)(p32;q11) Majority 70% are T lineage
lymphoma Pre B cell (-30%) marrow, skin, bone t(11 ;14)(p13;q11) with medlastinal mass >25%
Precursor T & B cells t(11;14)(p15;q11) blasts: Managed as leukemia
20% of NHL t(10;14)(q24;q11)
t(7;19;)(q35;p13)
Anaplastlc large CD30; anaplastic Lymph node, skin, bones, t(2;5)(p23;q35) Varied presentation; extranodal
cell lymphoma lymphoma kinase visceral, soft tissues t(1 ;2)(q21 ;23) nodal Involvement
10% of NHL (ALK, CD246), t(2;3)(p23;q21) Systemic symptoms present
epithelial membrane t(2; 17) (p23;q23) Prolonged waxing/waning
antigen pos~tive t(X;2) (q 11·12;p23) course
Inv 2{p23;q35) Diagnosis delayed and difficult
Essential Pediatrics
- 606
. ·~" .
. --~- r-:-· - • - • - ~- · -Hodgkin
•· lymphoma
Table 2·1 .16: st. Ju.de staging system for chlldho~d non
II IV
Diagnosis
Two/more nodal or extranodal areas on both sides of diaphragm
Any of the above with central nervous system and/or bone marrow involvement
Emergency Management
NHL are rapidly growing tumors and require prompt Life-threatening complications in NHL Include:
diagnosis. Selection of the appropriate lymp~ node ~r • Superior vena cava obstruction and caoplrngcal
mass for histological diagnosis is necessary. Histology is compression from mediastim1l mosses with lympho·
supplemented, where possible, with imrnunophenotypic blastic lymphoma
and cytogenetic studies. If the clinical condition is not • Airway obstruction from pharyngeal or intrnlhornclc rn;i~s
suitable for biopsy, due to a large mediastinal mass • Tumor lysis syndrome seen with lymphobl ns tlc
causing superior vena cava syndrome, the diagnosis may lymphoma and Burkitt lymphoma
be made with less invasive procedures including • Respiratory/cardia c compromise d ue to m a!l!:J ivc
percutaneous needle aspiration, examination of body pleural/pericardial fluid . .
fluids (e.g. pleural fluid) or bone marrow. All newly • Paraplegia from epidural tumor or raised 111tracran1al
diagnosed patients should be carefully staged (Table 21.16) pressure, and neurological deficit from intracranlil l
and worked up (Table 21.17). lymphoma or CNS involvement
• Obstructive jaundice and pancreatiti s f rorn
Management
compression of bile or pancreatic ducts
Improvement in survival has been possible due to use of • Gastrointestinal bleeding, obstruction, intussusccplion
highly effective chemotherapy and strong supportive care. and rarely perforation
Surgery has limited role in treatment, other than for These complications need to be recog nized enrly ilnd
diagnosis. Radiotherapy is restricted to emergencies, e.g., treated appropriately. Patients with superior mcd insli11,1J
spinal cord compression due to paraspinal disease. or vena caval syndrome require therapy with high dw.e
Multiagent chemotherapy, directed to the histologic IV dexamethasone. Tumor lysis s yndrom e m u ~I lie
subtype and stage of the disease, is recommended for anticipated and prevented by ensuring hydrnlion, and 11:.e
NHL.
of rasburicase or allopurinol; those with acute kid1 1<>y
injury or metabolic aberrations require hemodi n l y~ i s.
·Table 21·.11: Evaluation of a patient with non-Hodgkin lymphoma The cornerstone for treatment of pediatric NJ IL i ~
History and physical examination multiagent chemotherapy. Different chemothcrnpc11t ic
Complete blood count; peripheral smear examination regimens are used for treatment of 13 nnd T cl'! I
Liver and renal function tests, electrolytes, LDH, uric acid lymphomas. Most successful protocols arc the Gcm•:in
Biopsy for histology; cytochemical, immunologic, cytogenetics
BFM (Berlin, Frankfurt, Munster) protocols ilnd a m odified
and molecular studies version of LSA2L2 protocol. These are intensive protornls
Pleural, pericardia! or peritoneal fluid: Cytomorphology, immuno-
that use combinations of 8to10 drugs. Crani<l l im1 d inti on
phenotype characterization or prophylactic intrathecal chemotherapy is given in f>lilg': S
III and IV disease. Chemotherapy is give for a period of 1
Bone marrow aspiration and biopsy: Cytomorphology, immuno-
phenotype characterization
to 2 years depending on the stage and extent of the disease.
Radiation is recommended for specific indicntions, like
Chest radiograph (include lateral view if mediastinal widening)
CNS involvement. Long-term survival in patients with
Ultrasonography chest and abdomen lymphoblastic lymphoma with limited disensc is 80- 90%
CT scan/MRI of neck, chest and abdomen and for advanced disease 70-80%.
Positron emission tomography-CT (optional) Therapy for B cell (Burkitt, non-Burkitt) lymphornas is
Echocardlography different. Most protocols consist of short dura tion
(6 months) intensive alkylating high dose methotrcxatc,
Childhood Mallgnancles 1001 -
vin~"ristine, anthracyclines, etoposide and cytarabine. CNS of one RBl allele predisposes to cancer, while loHR of th'!
f1'."lphylaxis is provided with intrathecal chemotherapy. second allele, in developing retinal ceJIR, le11de1 to
Long-term survival is highly satisfactory with survival in retinoblastoma.
more than 90% patients with limited disease and 75-85% Retinoblastoma, a tumor of the embryonic neural retina,
in patients. with e xtensiYe disease. Survival rates in can be sporadic or inherited. Sporadic tumo rfi a rc
patients with bone marrow disease have also improved unilateral, unifocal and occur at an old er a ~e, while
dramatically. The use of anti-CD20 monoclonal antibodies inherited tumors occur earlier and arc often bilatcrt1 l and
m
(ritu,ximab) dire<:ted against B-cell antigens has been multifocal (Fig. 21.7a). The "two hit'' model of oncogc:mc11i11
combined with standard chemotherapy to improve proposes that two mutational evcntR arc required for
survival. Anaplastic large cell lymphoma may be treated development of rctinoblas toma, the firnt hit be ing a
either as Burkitt or as lymphoblastic lymphoma. The inherited mutation in IW1 and the second is acquired Jn
management of relapses is a challenge that requires the somatic retinal cell. In sporadic retinoblastoma both
intensive protocols and stem cell transplantation. mutations occur in the somatic retinal cell. Most cases of
hereditary retinoblastoma have a spontaneouA new
Suggested Reading germline mutation while their parents have wild type IW1
• Gross TG, Perkins SL. Malignant non-Hodgkin lymphomas in alleles. The risk of an offspring inheriting an RB1 mutation
dilldren. In: Principles and Practice of Pediatric Oncology. Eds. from a parent with germline mutation is 50%; 97"/,, children
Pizzo PA, Poplack DG. Lippincott Williams and Wilkins, with inherited mutation is at risk of rctinoblastoma .
Philadelphia, 2011; 663-82.
Germline mutations of RB1 also cause an increased risk
• Veronique Minard-Colin, Laurence Brugieres, Alfred Reiter,
~litchell S. Cairo, Thomas G. Gross, Wilhelm Woessmann et al.
of a second malignancy of the Jung, soft tissue, bladder,
Non-Hodgkin Lymphoma in Children and Adolescents: Progress skin, bone and brain; the risk is higher when these patients
Through Effective Collaboration, Current Knowledge, and receive radiation therapy for the retinoblastoma. A small
Challenges Ahead. J Clin Oncol .2015;33:2963-74. proportion (5-10%) of unilateral tumors is heredita ry.
RETINOBLASTOMA Clinical Features
Epidemiology The tumor arises from retina and grows towards the
vitreous. Its progression results in involvement of ocular
Retinoblastoma is the most common primary intraocular coats and optic nerve leading to scleral, orbit and central
tumor of infancy and childhood with an incidence of 1 in nervous system involvement. Hematogcnous dissemination
every 20,000 live births. About 90% cases are diagnosed may lead to distant meta s tas is. Le ukocori<1 ( \.v h ite
by the age 3-4 years and 98% by 5 years. One-third patients pupilla ry reflex) is the most common presenta tion
have bilateral disease, which is often multifocal and (Fig. 21.7b). Strabis mu s, poor vi s ua l tracking a nd
diagnosed at a younger age. The tumor is highly sensitive glaucoma are other presentin g fea ture s . O rbita l
to chemotherapy and survival rates in developed countries inflammation, hyphema and irregular pupil, phthisis bu I bi
are greater than 90%. (Fig. 21.7c) and a fungating oculnr mass suggest advanced
disease is often detected late, in developing countries,
Genetics
retinoblastoma either with a n orbit<il mass (propto is) or
The retinoblastoma gene (RB1), encoded on chromosome with distant me tastasis to the bones, born~ marrow, lymph
13ql4, was the first described tumor suppressor gene. Loss nodes and central nervous system.
Ag. 21.7: Retinoblastoma: (a) Familial retinoblastoma In two siblings; (b) A 3-year·old boy showing leukocorla; (c) A 3-yoar·old boy
With Phthisis bulbl
- 000
i ...
I
•
Opaque media from hemorrhage
Tumor necrosis, aseptic orbital cellulitis, phthisis bulbi
Diagnosis Treatment
The d ingnosis is based on history, clinical examination and The aim of treatment is survival with eradication of
imnging. Ocular examination of both eyes should be done disease; maintenance of vision and preservation of glob"'
under anesthesia. Imaging studies such as ultrasound, and vision are secondary goals. Treatment depends (•n
CT /MRI (preferred) scans are used to assess the orbital, size, location, extent of the tumor and whether it is
optic nerve and for intracranial extension. Rarely children hereditary or sporadic. Retinoblastoma is curable wht•n
with hereditary retinoblastoma show a pineal tumor the disease is intraocular.
(trilnteral retinoblastoma) that is detected on imaging. CSF Laser therapy: Argon or diode laser is the prim;uy
and bone marrow examination are done only if indicated
treatment for smaller tumors, but is also sometimes u!'t».i
on clinicnl examination or imaging. Biopsy or aspiration after chemoreduction.
cytology is not routinely required unless the diagnosis is
in doubt. Occasionally an adjacent lymph node needs to Cn1ot11erapy: A special probe applied through U1e sckr.1
be aspirated for metastasis. Screening for RBI mutations to produce low temperatures (-60 to-S0°C) is suitabl, for
on peripheral blood or tumor tissue, helps differentiate tumors smaller than 4 disc diameters dose to the retin.1.
somatic from germline mutations. C1iemot1ierapy: Chemotherapy enables salvaging the
affected eye, avoiding enucleation or external b1::im
Staging radiotherapy and risk of second malignancies. Systemic
Retinoblastoma may be intraocular or extraocular. chemotherapy most often comprises a combination of
Intraocular retinoblastoma denotes that the disease is vincristine, carboplatin and etoposide. Chemotherapy may
limited to the eye, and is confined to the retina or extends also be used for chemoreduction, as an adjunct modality
to the choroid1 ciliary body, anterior chamber and optic or for therapy of metastasis. Newer routes of drug
nerve head (Tables 21.18 and 21.19). Extraocular (melphalan, carboplatin) administration by periocular,
retinoblastoma refers to extension of the illness beyond intravitreal and intraophthalmic artery injection have
the eye, including tissues around the eye (orbital improved outcomes in intraocular retinoblastoma.
retinoblastoma) or spread to the central nervous system, En11cleatio11: In cases of unilateral disease with large
bone marrow or lymph nodes (metastatic retino- tumors where no useful vision can be preserved,
blastoma). enucleation is performed early. In children with bilateral
Chlldhood Mallgnanctes 1609 -
1l11J111lt:ill t1yt:ilU1lli11 d1011111lh1 rnpy IR 111wd lnlllnlly, followed kidney tissue "'.lied nephroi;enic ~ts. l\TT1 _is the~
hY l111'il l lr 1111tm o111 with lnllor phot11 con~1llnllun or chnrnctcrlzt'd Wllms tumor gene, with mutat:iOT1$ of th5
rry11!11urnpy ln 1ml11r In pniti1wv u vle1lon. Tho uyu with the gene obscrwd in npproximatcly 20% of Wilms tumors.
111111ti11f11l vl1:1lnn 11ho11ld bu 11n11d1i.1li 1l In thusL~ cnses. occnsionnlly in nssociiltion with mutatio n s in CTXJ\'Bi
(cntcnin beta 1; 3p22.1) ilnd WTX (gene on .X-chrom0$01ne).
/11111/11/11111·1111y1 l1x1t•niril hu11 111 rndlotllt'l'•lPY ft:l considered,
The WT1 gene is loc.ltcd on chromo:.ome l 1pl3 and
If 1 l11m111f humpy 1ll1 ~_1 fnc11l th1ir1lpy fnl I. J{ndlothcrnpy mny encodes for a trilnscriplion foctor that is critical for n ormal
ll111d tn n rhllnl dutormlly, liln:n ttyndromu, Ctllnrncls,
development of kidneys and gon;ids. l\TT2 is localized ro
rnillnll1111rullnnpnthy,1wovnHc11lnr ~1 ,111rnmn nnd risk of
a clus ter of genes at 11p15. Patie nts with \\}1 muo~.s
11 ti1tr11nd m 11 liKll1Hlcy.
have highe r risk of recurre nce and bilateral d i..<.ea..<:.e.
ll1•11111to1111/l'/l1' t>l1'111 1'111/ ll'1111s11/1111l11t/1111: Pnlients with Children with sonH.' genetic syndromes are predb~
µ11 lr11cir11h1r dftill1lHC! li.1vL• poor prognosis with respL•ct lo to Wilms tumor. These include WAGR (W ilms nunor .
1:1111·vlv,1l, Thn110 with n·~lonnl uxlrnoculilr di sease aniridia, genitourinary abnorm alities and mental
(lnvnlvlr1K nrbll, optic lll'l'VLl or prunuriculnr region) m ny retardation, WTl dcll 1p13), Denys-Dra~h syndro me
lw lrunl ud with n cornbinnllon of co nvcntionnl (renal failure, mesangial sclerosis, male herm.'lfh.rodit:h-m..
rlwn111llwrnpy nnd ox turnal bt.!<Hn rndlolht.!rnpy. Pa tients WT1 missen se mutati o n) and Beckwith-\\"ied e m.ann
with dltit·,1111 nwtnHlnsls rc.• quire high dose che motherapy, syndrome (hemihypertrophy, macroglo$Sia. omphal~e.
i1)(tum 11i l>c..mm rndlolhernpy nnd hcmntopoietic stem cell organomegaly, WT2 delllplS.5). Loss of h eterozyg053ty
trnnttplnnlnl Inn. of lp and/or 16q and high expression of telomer.l....~ are
associated with poorer outcome in \~ilms tumor.
rrogno5111
Mual l11nwn1 thnt arc confined to the eye are cured. Focal Pathology
tl wm py or unuclcntlon iH curalive in more than 95% of The histopa thology may be favorable (differen tiated
p11th•n1a with 11nllnter;;il dh;c;;ise. Cures ;;ire infrequent when blastemal, stromal and epithelial cells) o r unf.:n·orab.:?
cxlenRIVl' orbltnl or optic nerve extens ion has occurred or (diffuse or focal anaplasia, clear cell s.arcoma . rha.bdo:d
llw pnllenl hnR tliRtnnt metastas is. tumor). Most tumors are unicentric; 11 ':o are multirent:ric
Gmwtic counseling is an importnnt component of
mnnngc menl'. All fin;t degree relatives of children with Diagnosis
know·n or aw;pectcd he reditary rctinoblastoma should Most patients present with an asymptomatic abdominal
hilve n·~11lnr exnminalfon for evidence of ma lignancy until mass detected by their parents or physician during routine
7 ycm rll of age. examination. Features at diagn os is include: hem.atuP..3
(10-25%), hypertension (25%), abdominal pain (.3-0"").
Suggoated Reading fever (20%), anorexia and vomiting. Wilm.' turne r sho uld
• llhavna Chawla, Jfochna Seth, Lnxmi Moksha. Chemotherapy for be considered in any child with abdominal mass... Twr. r
Oc11IM Cnnct•rH. T rlmurthy Vclpamlian. Pharmacology of Ocular thrombus extending into the inferior vena ca\·a is found
'flwr.1pc11tics. Adis Springer. 2016:333- 58. . in 4-10%. O ther features at presentation include anemia.
Cm1turk S, Q,1ddo11111i I, Khc tan V, l'I al. Survival of rctmoblasloma
In li•HH dt•vclopcd countries, impact of socioeconomic nnd henlth
thrombocytosis, acquired deficiency of von \\'illebrand
n·lnled Indicators. Br J Ophthalmol 2010; 94; 1432-36. factor and factor VII, and polycythemia. Differential
• Ch.iwla II, JfaHan JI, Azad R, e t nl. Clinical presenta tion and s urviva l
11 ( n!tlnobln1itoma in Indian children. Ophthlmol 2016;100:172-78.
o Dirmira 11, Klmani K, Dimbn C!AO, ct al. Rctinoblnstoma. Lancet Table 21.20: Evaluation of Wilms tumor
2012; 379:1436- 46. Investigation Purpose
Abdominal ultrasound Organ of origin. identify
~ILMt!U~,~O~R~----------- contralateral kidney
WllmR tumor or nephroblastoma is the commonest Location of tumor thrombus in
malignant neoplasm of the kidney ~nd ~econd vena cava
mof!t common abdominal malignancy m children. CT scan Localization of tumor and
Approximately 6% of all childhood cancer is Wilms tumor extent of spread
with a peak incidence at 2-3 years of age. l~dividuals with Chest X-ray Pulmonary metastasis
horseshoe kidney have a higher risk of W1lms tumor. Bone scan, skeletal survey Bone metastasis. especially in
clear cell sarcoma
Gonetlcs Brain Imaging (MRI, CT scan) Brain metastasis in rhabdoid
While a vast majority of Wilms tumors are sporad.ic, tumor and clear cell sarct:lma
1-2% may be familial. Familial tumors ~ccur ~tan earlier Fine needle aspiration cytology Cytological confirmation of
ngc and have a high propensity for bem? bilateral. The tumor prior to chemotherapy
tumor is thought to develop in the foci of embryonal
Essential Pediatrics
- 610
- -~· - -~ •• -- - · -· ·· ~ . 1i mor Study Group)
Table 21.21: Staging for Wilms tumor (National W1lms _u . -
Tumor confined to the kidney and completely resected
Stage I
Renal capsule and sinus vessels not involved beyond 2 mm
Regional lymph nodes dissected and negative
· d Ith negative margins and lymph nodes
Tumor extends beyond the kidney but 1s completely resecte w .
Stage II 1
At least one of the following: (i) Penetration of renal capsule; (ii) Invasion of renal sinus vesse s
II Stage IV
Stage V
Tumor extends beyond surgical margins (microscopy, gross examination)
Tumor not completely resected because of infiltration of vital structures
Hematogenous metastasis, metastasis to distant lymph nodes
Bilateral renal involvement at time of initial diagnosis
• Fernandez C, Geller JI, Ehrlich PF, Hill AD, Kalapurakal JA, Grundy
diagnosis includes neuroblastoma and other flank masses
PE, Dome JS. Renal tumors.In: Principles and Practice of Pediatric
including hydronephrosis, multicystic kidney, and Oncology. Eds. Pizzo PA, Poplack DG, Lippincott Williams and
rarely abdominal lymphoma and retroperitoneal Wilkins, Philadelphia, 2011; 861-85.
rhabdomyosarcoma. Features of associated syndromes • Perlman EJ, Grundy PE, Anderson JR et,al. WTl mutation and
may be present in 10-20%. Evaluation and staging of llp15 loss of heterozygosity predict relapse in very low risk
Wilms' tumor are discussed in Tables 21.20 and 21.21. Wilms tumor treated with surgery alone. J Clin Oncol 2011;
29:698-703.
Treatment • Prasad M, Vora T, Agarwala S, et al. Management of Wilms Tumor:
The approach to treatment differs across the world. While CMR Conseesus document. Indian J Pediatr 2017;84:437-45.
the Childrens Oncology Group recommends upfront
resection of the tumor, the International Society of NEUROBLASTOMA
Pediatric Oncology (SIOP) recommends preoperative
chemotherapy without biopsy. The outcome with both Neuroblastoma, derived from the neural crest, is the most
approaches is similar. Upfront surgery provides accurate common intra-abdominal and extracranial solid tumor in
diagnosis prior to starting chemotherapy while children, accounting for 7- 8% of all cancers. This is a
preoperative chemotherapy shrinks the tumors making disease of early childhood with approximately 90%
surgery easier and decreasing the risk of spillage and patients presenting before 5 years of age and almost 50%
rupture. Radiation has limited role in the management. within the first 2 years of life. The etiology is not kno\'m
Patients <2-year-old with tumors <550 g with favorable but familial cases occur, and there is association with
histology are at low risk and m ay be treated with neurofibromatosis, Hirschsprung disease, heterochromia,
nephrectomy alone followed by close observation. Chemo- fetal hydantoin and fetal alcohol syndromes and
therapy for other stages I or II patients includes vincristine Friedreich ataxia. Rearrangement or deletion of the short
and actinomycin for 18 weeks. Doxorubicin and arm of chromosome 1 is present in 80% patients.
abdominal radiation are additional therapies for stage III Neuroblastoma is one of the few cancers that m ay undergo
illness. Cyclophosphamide, carboplatin and etoposide are spontaneous regression.
used for anaplasia and metastatic disease. Pulmonary
radiation is used for pulmonary metastasis. The pathology varies from extremely undifferentiated
Overall -90% of children with Wilms' tumor are long small round blue cell tumor (neuroblastoma) to tumors
term survivors. Young age, low stage and low weight with mature Schwannian stroma with ganglion cells
(<550 g) are favorable prognostic factors. Presence of (ganglioneuroblastoma and gan glioneuroma). The
anaplasia and loss of heterozygosity of lp or 16q increase characteristic histopathologic feature is the Homer-Wright
the risk of recurrence. Survivors of Wilms' tumor have pseudorosettes which are circular groupings of dark
relatively few late effects. Cardiotoxicity, renal failure, tumor cells surrounding pale neurofibrils. N euro-
second malignancy and pulmonary toxicity is reported in blastomas can resemble other small round blue cell tumors
survivors of advanced stage disease who receive intensive such as rhabdomyosarcoma, Ewing sarcoma and non-
chemotherapy and radiation. Hodgkin lymphom a, but are differentiated by
characteristic immune histochemistry. The pathology is
Suggested Reading closely correlated with prognosis, and tumors that show
• Buckley KS. Pediatric genitourinary tumors. Curr Opin Oncol 2012; better differentiation, more Schwannian stroma and low
24:291- 96.
mitosis-karyorrhexis index have favorable outcome.
ls11 -
Fig. 21.8: Nmuoblastoma. (o) ·1~accoo11's oyo' (lort oyolld) In a ct1lld with metastatic disease; (b) CT abdomen showing a suprarenal
mass SlJggestlVe of nouroblaslorno
r
Stage I
Toblo 21.22: International neuroblastoma staging
Localized tumor confined to the area of origin; complete excision, with or without microscopic residual disease;
Identifiable lpsllateral and contmlatoral lymph nodes negative microscopically
Stago II Localized tumor with lncomplelo gross excision; ldentlflable lpsllateral and contralateral lymph nodes negative
microscopically
Stage llB Locallzod tumor with complote or Incomplete gross excision, with positive lpsllateral regional lymph nodes; identifiable
contmlateral lymph nodes nogatlvo microscopically
Stage Ill Tumor Infiltrating across tho mldllne with or without regional lymph node Involvement; or unilateral tumor with
contralateral regional lymph nodo lnvolvomont; or mldllne tumor with bilateral regional lymph node Involvement
Stage IV n1mor dlssomlnatod to distant lymph nodes, bone, bone marrow, !Iver or other organs (except stage IV-S).
Stage IV·S Locnllzod primary tumor as dollnod for stage 1 or 2 with dissemination limited to liver, skin, and/or bone marrow
(llmltod to Infants loss than 1-yoar-old)
• 612 '
-- --- ---- - .. -- Table 21.2s: Management of neuroblastoma
Age. months MYCN Therapy Survival
Risk categol)'
ampliflcBtlon
No Surgery >90%
Low I Any
No Surgery; low dose chemotherapy >80%
UA, llB Any
IV..S <12 No Observation/chemotherapy/radiation
>75%
lntennediate Ill Any No Chemotherapy
IV <18 No Radiotherapy to tumor bed if residual
IV-S Any No disease present + second look surgery
II, Ill, IV Any Yes Multlagent chemotherapy + autologous 50%
\V..S <12 Yes bone marrow transplant + maintenance
IV >18 No therapy with 13-cis retinoic acid
Quantitation of serum neuron-specific enolase and children from infancy to 5 years of age. These may present
ferritin, amplification of i\ lyc-N gene, tumor cell ploidy as an asymptomatic abdominal mass; as disease progresses
and age-based histologic classification are of prognostic patients hnve abdominal pain, weight loss, vomiting and
value. Patients with neuwb\;.'lstoma can be divided into anorexia. Serum a fetoprotein (AFP) is a useful diagnostic
those with faYorable and unfaYorable features. The former, marker for disease assessment during and after completion
characterized b~ young age (<1.5 years), favornble stage of therapy. Tumor thrombi may extend into hepatic veins
(I, II and IV-S) (Table 2122), normal levels of ferritin and and inferior vena cava. Liver may become involved due to
favorable histology, has a sun ival expectancy of 90'% or metastasis from cancers which include lymphoma
more. Older patients with stage Ill or IV disease, serum (Hodgkin and non-Hodgkin lymphoma) neuroblastoma,
ferritin >150 ng/mL and h1mors of unfavorable histology Wilms tumor and desmoplastic small cell tumor. Benign
have survival rates of 20% or less. neoplasms of liver include mesenchymal hamartoma,
hemangioma, hemangioendothelioma, adenoma and
Treatment teratoma.
Treatment modalities include d1emotherapy, surgery and Diagnostic imaging includes CT or MRI of the abdomen
radiation therapy. Localized neuroblastoma can be treated along with the CT of the chest for evaluation of metastatic
by surgery alone and does not require chemotherapy disease. Complete resection of the tumor either by p artial
(Table 21.23). Patients with stage IV-S just require careful hepatectomy or by liver transplantation is critical for
observation. Chemotherapy is the d1ief of treatment for successful treatment.
advanced neuroblastoma. The regimens used include Hepatocellular carcinoma is an aggressive hep atic
OPEC (vincristine, cyclophosphamide, cisplatin, teniposide neoplasm affecting older children or adolescents. Children
(VM-26), CADO (vincristine, cyclophosphamide, with biliary atresia, infantile cholestasis, glycogen s torJ;e
doxorubicin) and PECAOO (vincristine, cyclophosphamide, disease and wide array of cirrhotic diseases are
doxorubicin, cisplatin, tenoposide). Other modalities predisposed to developing hepatocellular carcinoma.
include surgery, radiotherapy and autologous bone
marrow transplantation. Addition of cis-retinoic acid to SOFT TISSUE SARCOMA
autologous stem cell transplantation has been shown to
improve survival in patients with high risk neuro- Pediatric soft tissue sarcomas are a group of malign:<nt
blastoma. In all treatments good remissions are often tumors that originate from primitive mesenchymal tissue
reached, but the recurrence rate is high. and account for 6-7% of all childhood tu m o~ s .
Rhabdomyosarcomas account for more than half ot .111
Suggested Reading cases of soft tissue sarcoma in children. Other soft tissue
• Bansal D, Totadris, chinnaswamy G, et al. Management of sarcomas include fibrosarcoma, synovial sarcoma and
neuroblastoma: ICHR Consensus Document IndianJ Pediatr 2017; malignant peripheral nerve sheath tumors.
84:44fr.55. Soft tissue sarcomas may arise in any part of the body,
• Simon T, Hero B, Schulte JH, et al. 2017 GPOH guidelines for most common by the trunk and the extremities. These
diagnosis and treatment for patients with neuroblastic tumors. Klin neoplasms can present initially as an asymptomatic solid
Pediatr 2017;229:147~7.
mass, or may be symptomatic because of local invasion to
adjacent organs. Approximately 15-30% patients haYe
MALIGNANT TUMORS OF THE LIVER
metastatic disease at presentation, chiefly affecting the
Primary tumors of the liver are rare; over two-thirds of these lung. Other sites for metastases include the skin, bone,
tumors are malignant. Over 80% of malignant liver tumors liver, and lymph nodes. Treatment modalities include
in children are hepatoblastomas.The disease usually affects surgery, radiation and chemotherapy.
Childhood Mallgnencles j 613 . .
Rhcbdomyosarcoma
Osteosnrcoma is characterized by highly malignant
R}1Jbdonn-os.ucoma
. . • the co mmonest soft hssue
·
s an."tltntt, pleomorphic spindle cells with mnlignant osteoid
is J m.'lhgnant ~mor of skeletal muscle. Almost half of formation. Radiographic examination shows sclerotic or
the:;ecases are d1a£"nosed
0 ~
br :>years
- of age .md two-thirds lytic bone lesions nnd pcriosteal new bone formation over
b,· 10 yea.rs. the metaphyseal region. Biopsy is done to confirm the
. "J'.'e chi_ef sites are the head and neck (commonest), the diagnosis. Imaging studies include CT chest and
genitourinary tract and the e:-.:tremities. Orbital radionuclide bone scan to rule out metastasis; MRI
rhabdo~\yosarco~n.:i p_resents in young children with provides an accurate assessment of tumor extent.
proptos1s or swelling ot the e~·elid. Genitourinan• tumors
m.iy present as a pel_,·ic nuss , bladdt>r and prostate
~J.rge.me.~t or polyp01d mass in the Yagina. Almost one-
r,iurth pah~ts present with metastasis at diagnosis,
,~1mmor~ly m lungs,. bone marrow cmd bone. The major
Successful treatment requires complete surgical resection
followed by multiagent chemotherapy. Limb sparing
surgery by wide resection of the primary tumor is followed
by replacement of missing bone by prosthesis. Chemo-
therapeutic agents include doxorubicin, cisplatin,
I
h.J.~tologic types a.re: (1) Embryonal (60%), seen \\ith tumors i.fosfamide, cyclophosphamide and high dose methotrexate.
of ht>ad, neck and genitourinary tract, and has favorable The tumor is unresponsive to radiotherapy. With current
rn'"'gnosis; (ii) ah'eolar (20%) that is more common in older regimens, more than two-thirds of patients without
children, at the extremities and perinea} region and has metastasis are cured.
unfa\·orable outcome.
Rhabdomyosarcoma is curable in most children with Ewing Sarcoma
localized disease who receh·e combined therapy with Ewing sarcoma occurs most often in the second decade,
mOOications, radiotherapy and surgery, with more than but can occur below the age of 10 years. They most often
70~~ suni,·ing 5 ~ears after the diagnosis. Chemo- arise from flat bones such as pelvis, chest wall and
therapeutic drugs include vincristine actinomvcin vertebrae and the diaphyseal region of long bones.
cyclophosphamide and doxorubicin. ' ' ' Common sites of metastasis are lungs and other bones;
bone marrow metastasis is not uncommon. The typical
S.ONE TUMORS presentation is with pain, swelling or a limp, often
associated with fever and weight loss. Osteomyelitis and
05teogenic sarcoma and Ewing sarcoma are two major Langerhans cell histiocytosis particularly eosinophilic
bone tumors in children and adolescents. Both tumors granuloma are the chief differential diagnosis (Fig. 21.9).
occur commonly during the second decade of life and Plain radiographs show destructive lesions of the
show male predominance.
Osteogenic Sarcoma
Its peak incidence is during adolescence, correlating with
rapid bone growth. The distal femur and proximal tibia
are the most frequent sites followed by proximal
humerus and middle and proximal femur. Flat bones,
e.g. ,·ertebrae, pelvic bones and mandible are rarely
affected . Patients present with a localized painful
swellino 0
that mav be attributed to traumatic or infective
conditions, delaying the diagnosis by mon thsM
J
. etastasIS .
occurs earlv to the lunos and other bones. Germline
mutations ~f tumor su;pressor genes, including the
retinoblas toma (RBJ) gene are associated with increased ·.
incidence. Li-Fraumeni syndrome, associated with
germ.line mutations of the tumor suppressor p53 gene,
is characterized by increased incidence of breast can~er, _
soft tissue sarcoma, osteosarcoma, adrenocorhcal · ·'
carcinoma and leukemia in first degree relatives. High
d0se radiation therapy. such as that for Ewing sarcoma
or brain tumors, predisposes to development of
0 st~sarcoma, either in or at sites distant from the
Fig. 21. 9: Ewing sarcoma. Radlograph showing permeative lytic
radiation field. Benign bone lesions such as Paget d.i sease,
leslon with a prominent soft-tissue mass extending from the
lllu.ltiple hereditary exostoses, fibrous dysplas~a and
bone. Perlosteol reaction Is seen. The onion-skin (sunburst
enchondromatosis may ~asionally undergo malignant .. . PCiffern) indicates an aggressive proce5s suggesting Ewing
transformation to osteosaicoma. · : · · . sarcoma ·
- 614 j Essential Pediatrics
I
Fig. 21.11: Langerhans cell hlstlocytosls, (a) Radlogrort1 of F.hJll M1nwlna fylln l11~10m; ft 1) 111'7 !;l.1t/1flt itJU, sVirJ ltJ-;kA ~ ur.d Y-~JN!U-J
Langerhans Cell Hlstlocytosls (LCH) o( t1'<•lh, Ollwr m.1nlfrr-; tatl11n~ lttdtufo ~eborrht'ic. c:kiri
LCH is a rare non-ma ligncmt disease wilh unknown rntih (l'lg , ?. l , J ll>J In M ' ;1lp Mf! ti ;rnd bac k (W%),
etiology characterized by a clonal prolifornllon o( Iym phrt d 1•1111pa tl1y (T}'Y,, ) I hl'JM Iuc;p leru1r11 ega l y f'L.()'f,,,
pathologic cells with the chilrncteris li cR of I .angi·rhi'lllli tnrl1yp1wa, air IVi1k1;, p;u·i·rwhyrrwl lurrg infiltt<1fc<; (Vi't-.)1
cells in single/multiple sites nnd iln 1m1rn•d lctahl1• Ja11ndk1•, ahdoml rr a l dfot i;111.,Jor1 1 m:urodegcmcr11tlve
course. The clinical presentation iH hclcrow• 1wo11H 11ymplo111r; ;111d (1·;1t11ri•n Ii( 1rr;1lab1;urptim1 , Pitui tMy
ranging from single system involv<'m1•11t to a dytif11111:lln11 may ri·1> ult J11 growt h retardatlf/r1 .irrd
multisystem life threatening disea se (Table 21 .2<i). 'J'lw d iab1:t1• r1 I1wl pid IJI>. !)1:v1·n• d l1i(:t11:e iH characteri;r,f·rl by
hallmark of LCH is the presence of Birl>cck Kfillllrlt!tl fowr, w1·l1~hl lot>ri, rr1111i1IM:, failure to thri ve and l rn:r
(BG) on electron microscopy nnd poRitivity for S-100 dyri(11ncllo11. l,ivn lnv11lverr1 ·nt may n:1:ult in sclc:m'.1r1g
protein and CD1a positivity. The number of Lang1!rhan1> cholangiliH.tnd d rrhoi>it>. Bom.: marrow involvemen t m :1y
cells with BC Ciln vary in differcnt Jes iorrn, l,1111g1~ r!n lead lo a11 •mla and thrombocylope11ia.
(CD207) is a type JI transmembrane protein il RRnclal<•d
with BC and is presumed to be more senRitive and Dlag noala
specific thnn CD1a. Tlw cla1rnlc:al hir1lopatlw logl c foatun: of LCf I j<, the
The spectrum of LCH (eosinophilic grnnulom;i, I frtnd· prcs~n 1! of ll'11iona l hi11tiocyl1.:11 of l.C phc:notyp<·, :11ith
Schuller-Christain disease, Letterer-Si we disease) rcflccl's vnrying proportion 11( rr1<1 cropl111ge11, T Jymph 11(j!1·3,
varying extents of the disease. The course of dil:ieaRe iR cosinophilH11ncl m11ltln11de;1l1•d gi;mt cdl!-!. Th1: cell« '.:h1»1/
unpredictable, varying from rapid progression and death, pm1llivlly lo S-1 ()(),CJ Jl ii, ilrld lnng1:rin (CU 207); w~ MC
to repeated recurrence and recrudescence with chronic ~ccn on c!cctmn mknmn ipy. IJiag1101-1lic work up ~.hr11 Jld
sequelae, to spontaneous regression and resolution . incl udc h1op11y frtitn mo41 appr11pri;it1: Hite, complete bh1Jd
Patients with disease that is localized (skin or bone) have count, live r (unclion l<:HlH, c.:oaguhili<m H tw.Ji1:~, s k,~Jc. tal
a good prognosis and are felt to need minimum or t!Vcn rrnrvey, clw1it X· ray ancJ urine Hpecific gravity, Tl11::!>c
no treatment. Jn contrast, multiple organ involvement, include ultrnMound ahdorrH:n, CJ' ches t and or abdoml'n
particularly in young children (under 2-year-old), carriei; and MIH brain. Bon(! marrow hiopgicH are requirec.l to
relatively poor prognosis. cxclu'fo in(iltration .
The most common involvement is of the skeleton Trcatm1:nt for loc.a ll;r,cd diHca8c or Bingle bony lesion
(80%). Bone lesions can be single or multiple affecting varic!H (rom ohlH!fViltion, c urettage, indomethacin,
skull bones, long bones, vertebrae, ma sto id and bir,pfw,; plwnatl!i;, low do8c radiation to s yst emic
mandible. The lesions may be painless or present with chcrnothcrnpy. M11ltl r;y1'! lcrn <li Hcasc is treated with
pain and local swelling; X-rays s how sharp lytic lcRions chcmothernpy, c:ombinin1~ vinblaatinc, prcdnlsonc ilnd
(Fig. 21.lla). Clinical manifes tation includes vertebral 6-mcrcaptopurinc. ChilcJhoocJ LCH may hnvc long-term
collapse and spinal compression, pathological fractures scquclac some of which occur many years after completion
in Jong bones, chronic draining ears and early eruption of treatment.
Chlldhood Mallonrmclo•
,,------~~~----~~~~~~.=..:..;.:,;.;;;.;.;.;:.::.::-_::;::!.!.!!!!!!!.~::-----~~~~--~----
··---=~
r--: Table 21.27: Diagnostic criteria for HLH n tlrllJ uh~d to ilcJfcu.:IH Jn ' '-'"' tJtm 111 11.11t Jfll l YJll1rr A1111
HLH diagnosis establlshed, If ~ne of the two Is fu/fl/lod cytotoxic cdltt, fm1dl11y, In pfll l111l1>J1)l'Jtl w#i·1,ilit>111tf 'I orlJ~
Amolecular diagnosis of HLH (e.g. PERF, SAP, MUNC mutations) aniJ nwcrophilf$''H mid pmd11rllim of pr11l11ll.11m11111ltlf'j
i;yfoklntJH(lnhtrfomn y,;m11n111 l llflll>f l lJ!l-' ftr.; h f,y l11f AJ/1114
OR
1111d lntcrlm1klrni), Ymmr, 1 hlldr''fl '11Jfl1 I,,,, I n111J 'nJJr//11
5 of the following 8 criteria are fu/fllled
gene mutotlon.H1 or11 (,m1ll y l1l,,1my 1,f l '1 J I Aft'111~,1 r11JC:t1
•Fever
ilf'I huvlny, prJrn nry llLI I, 0/d,•r d1l"1tn1 'llH11 JIU f '''
• Splenomegaly
children wltho11l ld1mtlflablt· n11JtAfl1m~ "''! 1jµ:-,r r'H"i''IJ f,11
• Cytopenlas in at least two cell lfnes ha ve sccondnry or 1letjulr1•d HU I, tWt:.i1111JMj JIU 1 t1>
Hemoglobin <90 g/l Infection or other tilimull (1~.Y,, j1J vi-nl/J~ 11wum;;f1AJJ nnf1r'ltl~,
Platelets < 100 x 109/L SU!), DlflgnoRtlc cri teria t>f I fl JI J:; t>IVl'llll fr1 'fahJ~2.J ,ZJ,
Neutrophils <1 x 109/L
• Hypertriglyceridemia and/or hypofibrlnogenemla ONCOLOGIC EMERGENCIES
Fasting triglycerides >3 mmol/l (>265 mg/dL)
Oncologk em<!rgendcH 1rn1y pwt-;t·nl :c:1t dJ;;ypAh uf tfi'.:
Fibrinogen <1 .5 g/l malignancy, during courf.<' of tilt~ dl:-N1f.it or 1'~ ~ u 1't:-#/Vl"f lO!
• Hemophagocytosis in bone marrow, spleen or lymph nodes of therapy, A r;olJ<l tu mm 1n;1y Jnvmfo 1>r t;111npt1~j'; ·/it;.:I
• Low or absent activity of natural killer cells organ6 lik<! trachea, c6ophar,us '" 1;11p,~r1'1r v•.rr1:; CA '/tJ ,
• Ferritin >500 µg/L Effu 6lon t> into tlw p ll!ura l r;pM1: or p1~rk~ rdlum m ;;y
• Soluble c025 (soluble interleukin-2 receptor) >2400 units /ml comprominc functioni; ,,(I ung and l'w;ut, !'/fJ-t;J:;t;;-;J-, int/J tf;1]
brain may lead to C<'Tl!bral 1:d em ;-t ,1ruJ (1-a t !Jn -'1 ,,( rah~..0
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSES (HLH _ _ inlracranial leMion. Spinal omJ t 11m11r ln•1t;J·11;'1n1..-r;t f Ni'j JI~
to cord compression. Horw marmw in1ml'l1:rfll:tlt fl;";U!t:, i11
HLH is an aggressive and potentially fatal syndrome whkh anemia, bleeding due 1'> lhrmnboc:ylJ1f"'tli.a ''' urtJ~uJ;,!SIJrt
results from an inappropriate prolonged activation of abnormalitie1> (di 1H~afie I chcm1Jth1:rn py ), J 1~11Yc,-,t,,<:.i·;,
lymphocytes and macrophages (Table 21.27). HLI-1 is thrombosis, e<?r cbrova1Ku la r '~P' '"'''d '~h and in f,·<.ti1;n -s,
r~~~. Table 21.28: Common oncologlc emergencies: Clinical features and tmatmont
Emergency Manifestation Illness Troatmont
Tumor lysis Hyperkalemia (arrhythmia), hyperuricemla, hyperphos- ALL, AML, Hydration, i'.ifll'.>put'rrV'A,
syndrome phatemia, hypocalcemic tetany, metastatic calclflcatlon, NHL Burkitt raBb1Jrlc;;_~, ht:m'A~1J~'>
renal failure lymphoma
Hyperleukocytosis Thrombosis, stroke, pulmonary infiltrate, hypoxia Leukemia H ydration, nydmf-'jUrc:a
5
WBC > 10 /mm 3
Leukophr:rr;r,irs, d'l~rmtht::t<:VJ
Superior vena Swelling of face and neck; proptosls; difficulty In lylng NHL, ALL, Prompt 11".l~uo di~~r.o:.''
cava/mediastinal flat, breathing and swallowing; hoarse voice, Horner germ cell Storoi<h; fir~ r:NJ 01 rn:-~~r.:ttt
syndrome syndrome, wheezing, effusion (pleural/pericardia!), tumor Ch Qmoth1:mw1. rm1iatJcn
features of C02 retention (anxiety, confusion, lethargy, (rarefy u:;;P,(J in ct'liltJrcn)
headache, syncope) lntravonow; fint?j ln l?Yt!!r f.mb
Monitor for tumor lyc:b
Spinal cord Paraplegia, back pain, urinary retention, back pain, loss Neuroblastoma Prompt therapy with do.1..a·
compression of deep tendon reflexes, hypotonia Ewing sarcoma thasono
Lymphoma of Surgory occar>lonalfy tlJ!}uired
vertebral body Dofinltivo thorapy of tumor
Increased intra- Headache, emesls, hypertension, bradycardla, Ill and Medulloblastoma Dexamothason<J. curg:r..al
·cranial pressure VI nerve palsy, seizures Aslrocytoma lntorvontion. anticorrtul:::anu
Bralnstem glloma
Febrile neutropenia oral or axillary temperature >38.3°C (101"F), or two Child with Therapy whh arrt.it;lot.lc(o) and
consecutive temperature >38°C (100°F) In 12 hours malignancy on antifungal mc<Jlcatlona afl!Jr
period lasting at least 1 hour chemotherapy 3 dayn of lover
Neutropenla: Absolute neutrophll count <500/mm3
.. or <1 OOO/mm3 with expected decline sepsis, shock,
pneumonia, typhlltis (Inflamed cecum), DIC
Typhlitis Fever, neutropenla, acute abdominal pain, may Acute leukemia Supportive caro, IV antibiotics
progress to bowel infarction solid tumors consider G·CSF
- s1e I
-t m effects of cancer treatment, integrate them
Hormonal problems can occur because of paraneoplastic 1ong er · 'd f als t 'alls
secretions (Table 21.28). Metabolic complications may occur appropriately into society,. prov1 e relinerr d ~ sp~ ts
prior to/ at onset of chemotherapy following lysis of tumor as needed, offer psychologica1coW1Se g an ans1tion of
patients to adult care when ready. Th~ term long-term
=
cells. Therapy related complications include myocardial
dysfunction (anthracyclines), extravasation. of dr~~s survivor refers to patients who are disease free .for a
(anthracyclines, vinca alkaloids), hemorrhagic cystitis · · um period of 5 years. 92% children who were disease
(cyclophosphamide), cerebrovascular accidents (methotrexate, to s years, were alive at 15 years after diagnosis.
1-asparaginase) and pancreatitis (1-asparaginase,
Late Effects Associated with Childhood Cancer
corticosteroids). Early diagnosis and urgent management of
these conditions will save lives and allow for treatment of The common late effects of pediatric cancer comprise
the underlying malignancy. deficits in growth and development, organ ~ction,
I Suggested Reading
• Seth R, Bhat AS. Management of common oncologic emergencies.
Indian J Pediatr 2011; 78(6):709-17.
• Seth R, Singh P, Puri K, Arora A, Rathore AS. Morbidity profile
reproductive capacity and health of offspring and
development of subsequent neoplasms.
i. Growth and development: The components affected
include linear growth, sexual maturation,
and outcome of hyperleukocytosis in childhood acute leukemia:
musculoskeletal development, skeletal maturation,
experience from a tertiary center. Int J Hematol Res. 2015; 26:90-4. intellectual function, emotional and social
maturation (Table 21.29).
LATE EFFECTS AND SURVIVORSHIP ii. Organ function: Exposure to higher cumulative
With refinements in diagnostics and advances in chemotherapy and radiation doses required for more
therapeutics and supportive care the overall survival of biologically aggressive refractory disease increases
childhood malignancy has increased significantly over the the risk of both vital and nonvital organs toxicity.
past few decades. Over 80% children and adolescents with These include anthracycline related cardiotoxicity,
cancer survive 5 or more years from diagnosis in many pulmonary function abnormalities and, chronic liver
centers and are effectively cured of the disease. This is disease.
however at the cost of increased morbidity in the form of iii. Reproductive capacity _and pregnancy outcomes:
various late effects of cancer treatment. It is estimated that Reproductive functioning may be affected by various
a third to half of childhood cancer survivors will anticancer modalities (surgery, chemotherapy and
experience a late term effect of cancer therapy; of which radiation). Alkylating chemotherapy is toxic to the
up to half may be life threatening. gonads. They produce a dose related gonadal germ
The main goals of the Cancer Survivorship Program are cell injury. In boys, alkylators damage germ cells
to improve the health and well-being of childhood cancer leading to infertility. Compared to boys, girls
survivors by promoting adherence to a schedule of follow- maintain an ovarian function at higher cumulati\·e
up appointments and routine screening tests, educate doses of alkylating agents and if dysfunction occurs
patients, parents and healthcare professionals about the it is often reversible.
is seen at doses of 1-3 Cy but is irreversible at higher following high dose myeloablative therapy. Higher doses
doses (>3 Cy). Prepubertal status does not protect of myeloablative chemotherapy can be administered than
from germ cell injury. Abdominal, pelvic or spinal is otherwise possible. There is no risk of graft rejection or
radiation also contributes to germ cell depletion in GvHD. This approach was initially restricted to solid
girls. Ovaries of younger girls are more resistant to tumors (neuroblastoma, germ cell tumors, retinoblastoma,
radiation damage as compared to ovaries of older medulloblastoma) where bone marrow was free of disease,
women. Radiation doses >20 Cy cause irreversible but is now being used for hematological malignancies and
ovarian failure and doses between 20 and 30 Gy
delay pubertal development. lymphomas.
iv. Second maliguatit 11eoplasm (SMN): Pediatric cancer
survivors are at an increased risk for development
of second cancers; host factors (genetics, immune
function, and hormonal status), primary cancer
Peripheral HSCT: CD34 positive cells are mobilized.fr~m
marrow into circulation in sufficient numbers for clinical
use by use of recombinant human hematopoietic growth
factors. These cells can establish durable marrow
I
therapy, environmental exposure and lifestyle engraftrnent.
factors play a role in the occurrence of secondary
neoplasms. Common malignancies that occur as Umbilical cord transplantation: Cord blood banks are
second neoplasms include acute myeloid leukemia another source of stem cells. The graft composition and
(AML) including myelodysplastic syndrome and biological properties of umbilical cord stem cel!s a~e
solid tumors. Secondary AML commonly develops different from adults. Cord blood transplantation is
in association with use of alkylating agents or associated with enhanced engraftment and reduced
topoisomerase II inhibitor therapy. Radiation incidence of GvHD.
therapy is also implicated in the occurrence of SMNs
like acute leukemia and solid tumors involving the Uses of BMT
breast, thyroid, CNS, bones, and soft tissues. The Allogenic BMT is indicated in all patients of acute myel~id
latency for occurrence of SMN varies from 2-3 years leukemia after the first remession, except these with
to as long as 10 years. Breast cancer is the most favorable cytogentics and good risk group which includes
frequently reported secon~ar~ s~lid tumor. in acute promyelocytic leukemia with translocation t(l5;17),
childhood cancer survivors with incidence varymg t (8;21) and inversion (16) or low levels of minimal residual
from 10 to 20% by 20 years from radiation. disease.
BMT is indicated in patients with acute lymphoblastic
BONE MARROW TRANSPLANTATION (BM!) leukemia during their first remission and a risk factor
BMT is the established therapy for congenital or acquire.cl including hypodiploidy, t(4;1 l) biophenotypic leukemia
disorders of the hematopoietic system and hematologic and high minimal residual disease after induction.
malignancies. Transplantation is also indicated after second and
subseqent remissions.
Allogenic hematopoietic stem cell transp~a~tation (hHSCT) BMT may also be considered for various non-malignant
d and a rec1p1ent w o are
occurs between a 0 .nor d t aft vs host disorders, e.g. severe combined immunodeficiency,
immunologically identical. It can lea 0 grd t Wiskott-Aldrich syndrome, severe aplastic anemia and
disease (CvHD), where immune cells fr~~ t~:cti~~o~~=~e storage disorders.
against antigens on host cells and gra reJ
h t lls destroy donor stem ce11s
immune compete~t os ~e he risk of relapse of Suggested Reading
before the graft 1s established. T · HSCT
. I following a 11ogemc • Guilcher GMT. Hematopoietic stem cell transplantation in children
malignant disease 1s ower aft on malignant cells. and adolescents. Pediatr Rev 2016;37:135--44.
because of immune effects of the gr
Chapte r
22
Rheumatological Disorders
Surjit Singh
Reactive arthritis This has become less common in our experience. !t can
' Systemic lupus erythematosus, dermatomyositis or polyarteritls result from actual infection with Mycobacterium tuberculosis
nodosa
or from an allergic phenomenon (Poncet disease). The
~o~mer us~ally presents as mono-arthritis (e.g. hip or ;inl<le
Associated with leukemia or neuroblastoma
JOmt) while _t~e latter pr~scnts as polyarthritis with a
Associated with Lyme disease or brucellosis strongly positive tubercuhn reaction. Arthrocentesis may
·Sickle cell disease be diagnostic (Table 22.2).
Associated with hypogammaglobulinemla
Reactive Arthritis
Chronic arthritis (>6 weeks)
This is not as common in children as in adults. It i.5
Juvenile idiopathic arthritis diagnosed on the basis ~f Berlin criteria: (i) peripheral
Ankylosing spondylitis arthritis, usually low~r limb, asymmetric oligoarthritisi
Tubercular arthritis (ii) evidence of preceding .gastrointestinal or genitourin~
infection (usually by Shtgella, Chlamydia or Yersinia), J!1
Legg-Calve-Perthes disease absence of clinical symptoms and (iii) exclusion of other
Psoriasis arthritides.
620
•
__________________.!R~h~e~u~m:!!!at~o~lo~gf!!l~ca~l~D~l~s~o~rd~e:.!r!s_ _ _ _ _ _ _ _ _ _ _ _ J 621 -
A s~all proportion of children with acute lymphocytic of one or more joints with onset below 16 years of age and
leukemia show bone and joint pains. Bone pain, that is persisting for at least 6 weeks. It has the following .subtypes:
more marked at night, is the predominant complaint in i. Systemic
affecte~ children. Hemogram shows lymphocy tic ii. Oligoarthritis: (a) persistent (b) or extended
predommance and thrombocytopenia, in contrast to a iii. Polyarthritis: Rheumatoid factor n egative
polymorphonuclear predominance and thrombocytosis iv. Polyarthritis: Rheumatoid factor positive
characteristic of juvenile idiopathic arthritis. A bone
v. Psoriatic arthritis
marrow examination is required to confirm the diagnosis.
vi. Enthesitis-related arthritis
X-linked agammaglobulinemia (Bruton disease) may
sometimes present as an unusual 'aseptic'arthritis (due vii. Undifferentiated arthritis: that (a) fits no other
to Mycoplasma infection), but accompanying respiratory category; or (b) fits more than one category
infection is usually present. JIA is not rare; its estimated prevalence ranges from
Arthritis can, at times, be the presenting complaint of 0.4 to 1.3per1000 children below 16 years of age. It is the
hemophilia or human immunodeficiency virus infection. commonest rheumatological disorder of childhood and
one of the most common causes of disabilih·, chronic
Legg-Ca/ve-Perthes Disease morbidity and school absen teeism. While West~m studies
suggest that JIA is more common in girls, in India, female
This is characterized by an avascular necrosis of the
predominance is not marked.
femoral head, occurring usually in boys 5-10 years of age.
. Systemic JIA (sJIA) is now considered to be a separate
It may be a manifestation of an underlying h yper-
d~sease a~toget~er. It is classified as an auto-inflammatory
coagulable state (hypofibrinolysis or deficiency of protein
disorder m which the innate immune system is primarily
C or S). Familial occurrence is commmon and the condition
affected unlike other types of ]IA which represent defects
is bilateral in 10% patients. Affected children present with
of acquired immunity. The ILAR definition for sJIA
a painful limp. Initial X-rays may be normal. Isotope bone
requires that fever be present for at least 2 weeks and
scans and magnetic resonance imaging are required to
should be accompanied by one or more of the follo"ing:
confirm the diagnosis. Subsequ ent X-rays show a
Evanescent rash, generalized lymphadenopathy, hepato-
characteristic sequential progression: (i) Widening of joint splenomegaly or serositis.
space, (ii) fragm entation of epiphysis with patchy areas
of increased lucency or density, (iii) abnormalities of shape
Etiology
of femoral head and neck, and (iv) d eformed head.
Treatment options include femoral varus osteotomies or The immune system is intimately involved in the evolution
containment splints. of JIA. HLA DRS and DRS are linked to early onset
oligoarthritis (seen more often in girls), 827 to late onset
Juvenile Idiopathic Arthritis oligoarthritis (seen more commonly in boys) and DR4,
The term juvenile idiopathic arthritis OIA) was proposed Dw4 and DRl to rheumatoid factor positive polyarthritis.
by the Pediatric Standing Committee of the International JIA is not a homogeneous disease and the different
League of Associations for Rheumatology (ILAR). It refers subtypes may represent separate clinical conditions.
to a group of conditions characterized by chronic The etiopathogenesis of ]IA remains an enigma. Several
inflammatory changes of the joints. It is defined as arthritis environmental triggers (e.g. infection with rubella virus,
- s22 I Essential Pediatrics
parvovirus B19, M. t11berc11losis, Mycoplasma pneumoniae Polyartliritis: Polyarthritis occurs in 25-30% of patients
and cntcric organisms, physical trauma or psychological and is more common in girls.Joint pain, out of proportion
stress) are linked to the onset of JIA, but their exact role is to the degree of joint swelling, is the usual complaint. Fever
not clear. Cytokincs like tumor necrosis factor-a (INF-a), and malaise can be significant. Two subtypes are known:
IL-6 and IL-1 have to have an important role to play in Rheumatoid factor negative: This subtype may occur at any
the pathogenesis of the disease. A number of auto- age in childhood. Knees, wrists and hips are the joints
nntibodies (for instance, antinuclear antibody) may be seen usually affected. Small joints of hands and feet are less
in the sera of children with JIA. The classical IgM commonly involved and rheumatoid nodules are not seen.
rheumatoid factor is almost never detectable in preschool Joint disease in this subtype of JIA is far less severe than
children with JIA. Older girls with polyarticular small joint that seen in patients who are rheumatoid factor positive.
disease of the hands (especially involving the
metacarpophalangeal and proximal interphalangeal Rheumatoid factor positive: Age at onset is late childhood
joints) may, however, be RF positive. or early adolescence. The arthritis is symmetrical, additive,
severe and deforming and typically involves small joints
I Cllntcal Subtypes
Three major types of onset are described according to the
presentation during the first 6 months of disease, namely
systemic JIA (with fever and rash), oligoarthritis (4 or
of hands, especially the metacarpophalangeal and the
proximal interphalangeal. Cervical spine and temporo-
mandibular joints can also be affected. This subtype is the
only category of JIA which is somewhat similar pheno-
typically to adult onset rheumatoid arthritis. Rheumatoid
fewer joints involved) and polyarthritis (more than 4 joints
involved). nodules are present in some patients and they usually
indicate severe disease.
Systemic /IA (s/IA): About 5-15% of patients withJIA may
have acute onset disease with prominent systemic Psoriatic artliritis: Psoriatic arthritis is said to be present
features. These systemic features may sometimes precede when there is arthritis in association with psoriasis or any
joint manifestations by weeks or months. This condition 2 of the following features-dactylitis, nail pitting and
should, therefore, be considered in differential diagnosis psoriasis in a first degree relative. Arthritis may precede,
of any child with prolonged fever. The illness can occur accompany or follow occurrence of psoriasis in children.
at any age and is more common in boys. Clinical features suggestive of psoriatic arthritis include
It usually begins as an intermittent fever with a simultaneous occurrence of small and large joint arthritis
characteristic twice daily peak. Fever is generally more or involvement of distal interphalangeal joints.
prominent in evening. It is accompanied by an evanescent Enthesitis-related arthritis: This condition is more
maculopapular truncal rash. The rash may be difficult to common in boys, typically older than 8 years. Asymmetric
recognize in individuals with dark skin. Affected children large joint (e.g., knee, ankle, hip) involvement of lower
show marked irritability that decreases with subsidence extremity is characteristic. Many children are HLA 827
of fever. Serosal involvement (in the form of pericarditis positive, and a proportion of these may go on to de\·elop
or pleuritis) may be prominent. Hepatosplenomegaly and ankylosing spondylitis later as adults . HoweHr,
lymphadenopathy are common at presentation and sacroiliitis and spondylitis are usually not significant till
can lead to diagnostic confusion. There is moderate late adolescence. Self-limiting acute symptomatic iritis
neutrophilic leukocytosis and an elevated erythrocyte may occur in some patients but it does not progress onto
sedimentation rate along with thrombocytosis. the chronic iridocyclitis seen in oligoarthritis of young
Rheumatoid factor is negative. girls. A family history of ankylosing spondylitis, psoriasis,
Oligoarthritis: Oligoarthritis is the most frequent type of Reiter disease and low back pain may be obtained in these
JIA accounting for approximately 60-70% of patients. Four children.
or fewer joints (usually large) are affected during the first
6 months of disease. Joint swelling, rather than joint pain, Laboratory Investigations
is the usual complaint. Two subtypes are described: The The clinician should recognize the differing patterns of
term persistent (if number of affected joints continues to joint involvement in various types of JIA. This 'pattern
be 4 or less) and extended (if number of affected joints recognition' is often the most important diagnostic clue.
exceeds 4 during the disease course). Laboratory investigations may be of a little or no help in
Oligoarthritis is more common in young girls, typically arriving at a diagnosis.
3-5 years of age. Asymmetric involvement of knee or ankle Synovial fluid aspiration for microscopy and culture is
is characteristic. Small joints of hands and feet are not indicated in children with rnonoarthritis because septic
involved. Asymptomatic, and potentially blinding, arthritis may need to be excluded (Table 21.2). Complete
iridocylitis can be seen in 25% patients with early onset blood counts should be requested along with a.n
oligoarthritis, and is especially common in girls with erythrocyte sedimentation rate. Acute lymphoc~tic
antinuclear antibody (ANA) positivity. leukemia can sometimes have an arthritic presentation,
Im -
B children m ay b e nustakenly
and such . dlngnosl'd ns hnvlng rofProxlh, vold1•i'oxll') J111w~ Jow11rwi!Jtr1>Jt1l1!::.t111:,J ~·1~1~
JIA· one m~rrow aspiration is therefore nccessnry If \\RO Offl1 CIR, hlll rl nl IH>l t'1•~'1Jltltl'l'!lldetJ for Uli'~ Jrl d 1l1.d tf.:Jl,
of glurocorticoids is being contemplated fol' ll'~Mnwnt of Althm1~h lllll 11w1fo1nl1in1 ,,( a tl1m of ,,11 1'JtjAJlh fa ti~
JIA· Rfllllt?,ldlt1r1yncrri lk n•rip1111 r;1•N a m well IM11l'lm •md /j r)·1~
C-reactive
. protein·
. . n smTogntc mnrkcr
measurement is pr1tll·11l mny r1•rip1md le> cm•• Nf}AJO anti n<1t v1th.1! ofht." f,
of ~sease activity and is helpful nn follow-up. Plnln Rl•:'lponlit! lo tlwmpy h LJl)tJally 1>low ancl thi!) fad 11w~t ~
~diogr~phs of affected joints are obtained nt thrn! of lnlllnl ~xplnhwd lo till! paret1lt1. Tn~ahm.mt mu~t contJmu.t fur tJt
diagnosis and may be repeated for 11sscssnwnt of erosive l~nsl ·1-6 Wt!Ckr> before il <lcd t>lon to tswltch 1m:r tn i#llAh .1.ff
diseas~. It should be noted that screening for rheumntold NSAll) lr1 nrndc~.
fa~r isnnot a m~e~l test for diagnosis of nrthrilis In young Dlst•nlltJ mocJlfylny, •mtl·rheumatic dru~:) (JJMAJ{l.J?,)
ch1ld:e , but it is an important prognostic factor In 1wt~d lo bl• Hllll'h!u 111 ulrltolit all chlldrt'n wHJ1 P''Jy~rthrith
situations where it is positive. Wll\!kly 11\t! lhotn~ xatc (1 5- 25 n1g/m 2/ w1!f:l-. giYen
s11bc11hmcmrnly or orally) hw>!>implified 1Mnarp m.1:nt uf
Treatment St.~ vt•rt~ (ornrn of JJA. Children l>f!l! lfl to tol er ;;te
•
Managemen! of JIA is multidisciplinnry. Physlothernpy nwtholn!xnle bt!llcr than ;1dult,; nnd have fower (jdw:r~
and occupa~on~l .therapy should be tnilored to specific c(focts, On ''~ the d1ild i» i11 ~table remh!:Jiun ( u o,u~ JJy
n~ of an m~_1ndt~al child, in order to prevent dcfor· nchic•wd aflt~ r Ht!Vl'fill month1;), the drug can b~ tapered
nuti~ and facilitate mainstrenming' nnd rchnbilitntion. lo the minimum dfoc.:ti ve dorw a nd then i,topped ,
Physical therapy helps in relieving p11in, mnintcnnncc of Mclhntrcxnlt! Hlwul<l alwayHbr! given under cl1r)l! medical
posture and joint mobility, improves muscle strength nnd supervision. Pc!riodk lc1; ling of Jivf!r fun ctl o n i; is
prevents fixed flexion deformities. All pntients with JIA mandatory. Dl'Vlfopm enl of hepatic fibmsi.,, a dreaded
need to be assessed by an ophthalmologist so thnt uvcitis ndvc rs~! dfc•d, ii-i un «11nmon. f lydmxychl<mJquine i5 a
can be detected early and treated uppropriatcly. Children useful adjund and ii; often ui;e<l along with mltlhotri:.xatf:',
with oligoarthritis need regular ophthnlmologknl follow- LcflunomiJ c, nn inltibilur of pyrimidine synthebiE, ha!>
up as uveitis can develop later. been uscJ in aJultHwith rheumatoid arthritis,
lntrn-articular injections of glu cocurticoicfo (usually
Medical t11erapy: NSAIDs are the mainstny of symptomatic
triamcinolone) arc the preferred therapy for childnm with
management. The com·entional NSAlDs inhibit both
oligoarthrilis who do not rci;pond to an initial trial of
isoforms of the enzyme cyclo-oxygcnnsc, i.e. COX-1
NSAIDs. Systemic glucocorticoidi; (usually prednisolon~
(constitutive; mediates physiologic prostaglnndin
1-2 mg/ kg/ d11y; occa sionally methylprcdni ~o l on e
production necessary for gastrointestinal mucosa I integrity
10-30 mg/kg) arc nccci;sary for se vere unremitting
and adequacy of renal blood flow) and COX-2 (inducible;
arthritis, systemic manifc1>tations (e.g. p cricardi tis,
mediates pathologic prostLlglandin production, especially
myocardilis, vnsculitb) nnd rapidly progresi;ive d isease.
at sites of inflammation). NSAIDs commonly used in
Prcdnisolonc, when used in thi s manner, is us ually given
children are naproxen and ibuprofen. lndomcthacin is
as bridge therapy for n few weeks while awaiting the
believed to be of particular use in enthesitis related arthritis.
clinical res ponse of methotrexate.
Doses of commonlv used NSAIDs are given in Table 22.3.
lridocyclitis warranl1; therapy with local s teroid
Development of Reye syndrome is a d~stin~t possi~ility
instilln lion ;m<l m yd ria lie eyed rops. Weekly methotrexa te
while a child is receiving NSAlDs, especially 1f there 1s an
therapy is required for pnticnts with severe uvcitis .
interctment viral illness. All children with NSAIDs must
Newer moJalitics of treatment includ e recently
be monitored for gastrointestinal adverse effects. The
introduced biological agents like anakinra (IL-1 receptor
recently introduced selective COX-2 inhibitors (e.g.
antagonist); cm1akinumab (monoclonal antibody to JL-1);
tocilizumab (monoclonal antibody to IL6 receptor);
1--- ·-
r. .. Table22.3: Doses of commonly used NSAID~ infliximnb, golimumab and adalimumab (monoclonal
l
Dose, Maximum dose, Frequency of antibodies to TNF-r:t.); etancrccpt (recombinant soluble
mg/kg/day mg/day administration TNF receptor p75 fusion protein) and abatacept (inhibitor
750 Twice dally of T cell activation). Etanerccpt and infliximab are
Naproxen 15-20
Four times
powerful biological agents against TNF-u.. While
Ibuprofen 35-45 2400
dally etancrccpt has been used in children with polyarthritis
not responding to mcthotrcxatc, infliximab has been more
1-2 150 Three times
lndomethacin commonly used in adults with spondyloarthropathy.
dally
Tocilizumab and anakinra have found favour in children
2-3 150 Four times
Diclofenac with severe forms of sJJA. While these biologics are
dally
now being incrcnsingly used ns first line therapy in children
0.3-0.6 20 Once dally
Piroxlcam with JIA, long-term safety of these products remains
The analgesic dose Is usually half the anti-Inflammatory dose unclear.
Essential Pediatrics
~
0 )IJ(f.fl severe and has a poorer prognoois ~an adult SU. The
011)Wilrlhrilla 11121111lly htis ti good prognosis but localized
o!
hallmark of SLE is the presence anbnuclear anlibodi~
(ANA). Marked female predo~anre characteristic Cli
d,jfPrrnilir.ti con develop due to Miymmetric growth of adult SLE is usually not apparent m young children.
lln1l112. C hildn~ n with enlhesitis related arthritis can
dt!\'~ l11p bpond yIi tis and sacroi Iii tis later, especially if they
Diagnosis
iHfj I II .A 1127 poAitlvC!.
Diagnosis of SLE is fac~litate~ ?Y Systemic Lupus
Chlldn.in with rheumatoid factor positive polyarthritis International Collaborating Climes (SUCC) critena
lH\V li 1' 'liHIH\!IC pattern almilar to adults and fihow erosive
(Table 224). However, SLE is ah~·ays ~~cal diagnosis--
{\IHI d1 formln~ ilrthrltis, Prognosis ifi better for
the criteria mereh· prm;de helpful gwdelines fur r~achin.,
~~rllnl!~i\llvo polyMthrilla as remissions are obtained more
a diagnosis. In. man~· ~a~~ts. especially childr~
oftl:n i\nd rctiidual joint lesions may be minimal. treatment ma\· ha\·e to be uutiated eYen when they do not
Tlw co11rnc: of 11ys tcmic onset disease can be extremely fulfil the reqttlsite criteria.
varli\hlo il lHI rc:nponsc to therapy is not always satisfactory. The maiar rash, which is Yirtually pathognomonic of
lnil ppropria tcly trciltcd or untreated patients with JIA SLE, may not be apparent initially. It inYoh·es the cht>ek,
"'''Y dCV<!IOp flcxlon contracturcs of hips, knees and bridge of nose and lower eye.lids but ':11ar~c~stically
• . l' lhl1Wt•. rl!Hllllinf; in permanent disability. Neck stiffness spares the nasolabiaJ folds (Fig. 22.la). Di.'C01d lesions a.r~
1~1 iln t·~iprclally debilitating problem and can result in rare in childhood on...~t SLE Oral ulccr,1 tions may in\'oh·t'
IClrtlcolliti. Tcmporom;mdibular joint involvement results the buccaJ mucosa or palate and are usually painl~'-"· Somt-
In n·strlct<·d ope ning of the mouth and may require children may have prominent frontal alopecia (Fig. 22.lb).
~ 11q~k11l inl'crvcnlion.
Arthritis is generally mild and always non-erosi\'e.
Renal inv olvement is a dreaded complication oi SLE
Compllcaf/ons and one of the commonest cau..~ of mortality in children.
A1wmii\ 1 due to chronic ongoing inflammation, is almost Lupus nephritis is com·entionally classified J.$ iollmrs:
alwi\y~ prc~l'nl in children with persistent active arthritis Class I: ~vfinimaJ mesangial; O a..;;;s II: ~Ies.mgial proliil'.r.1tiYe;
nml Sl·rlill hl'moglobin levels mirror disease activity. Blood Class fll: Focal proliferatfre; Cla..'S I\!: Diffuse pn liil'rJti\-e;
loi'i~ lnducc·d hy NSAlDs ciln also be a contributory factor Class V: Membranous; Clas.:s \ J: AdYanced s.:krnsin.g.
for tlw i\ncmlil . Chronic anterior uveitis may be clinically Class ill and Oass IV lesions (i.e., proliferath·e gl0m~rulo
~llc•nt nnd potentinlly blinding. Girls below 6 years of age nephritis) require the most a&:>oressh·e forms oi th~rJpy.
with oli~<li\rthritif'!, and who have antinuclear antibodies,
nrn nl the hl~hcst risk of developing this complication.
Children with sjfA nre especially prone to develop Table 22.4: SUCC Classification Criteria for S E
mncrophn~c activation syndrome. This is a potentially Requirements: <?:4 criteria (at least 1 clinical and 1 b l ~ratory
foli\I complication that presents with unremitting fever, criteria) OR biopsy-proven lupus nephritis with po$1: ~t·~ ANA
tiuddl·n onset ictcrus, bleeding tendency, leukopenia, or anti-dsDNA
thrombocy topcnia, h ypofibri nogenemia, elevated Clinical criteria
trlglycC'ridcs nnd raised ferritin levels. Prompt adminis- Acute cutaneous lupus
tt·atlon of Intravenous methylprednisolone pulses can be Chronic cutaneous lupus
llfo S\Win~. Oral or nasal ulcers
Growth disturbances, limb length discrepancies and Non-scarring alopecia
joint cnntracturcs can be seen in children with long- Arthritis
standing discnse. Growth failure may occur secondary to Serositis
severe inflammation or treatment with glucocorticoids. Renal involvement
Trcntmcnt with recombinant human growth hormone Neurologic involvement
mny be an option in children with growth disturbances. Hemolytic anemia
Secondary mnyloidosis is a rare complication that presents Leukopenia
with asymptomatic proteinuria and hypoalbuminemia, Thrombocytopenia {<100,000/cu mms)
nnd is often irreversible. Immunologic criteria
Antinuclear antibody (ANA)
SYSTEMIC LUPUS ERVTHEMATOSUS Anti-dsDNA
Anti-Smith
Systemic lupus erythematosus (SLE) is an autoimmune Antiphospholipid antibody
disorder characterized by inflammation of connective Low complement (C3,C4,CH50) iG
tiss ues and blood vessels resulting in multisystem Direct Coombs' test (do not count in presence of hemotYt
involvement. Clinical manifestations are variable and the anemia)
course unpredictable. Childhood SLE is usually more
, . , . - - - - - - - - - -_ __ _ __!R!!.h~o~
um
=:et::o::::lo:.!!o~lc~Q!..I!:!
DJ!!s!!or~d~tt!.!rt~---------- I 625 -
Fig. 22. l: Systemic lupus erythematosus. Note (o) Molor ro~ti; OrYJ lbJ Fru~~ d/.Y';Y./J.t;
Neurological features include psychosis, seizures, U6c of monthly pulM?'6 uf IV cydaphosphamide (500 mg/
alterations in sensorium, focal deficits and chorea. There m2) has cons iderably impm,1e<l the long-term outcome in
maybe no correlation between severity of clinical involve- children with i;cvere form"? of lupus nL-phritis. Once
ment and findings on neuroimaging. Hematologic remission is achieved, Hu: patiL-nt can be maintained on
abnormalities include Coombs' positive hemolytic anemia, mycophcnola tc mvfotiJ ''' ai'~thiavrim:. Mycophenolate
leukopenia, lymphopenia and thrombocytopenia . In mofotil is bcin~ increar,in)jly u.<Y..:d for th£.-rapy of severe
addition, there may be coagulation abnormalities due to forms of lupus nephritis in child ren.
presence of antiphospholipid antibodies . Cardiac Low dose prcdniM>lom: (25-3 mg/day) and hydroxy-
manifestations include pericarditis, myocarditis, or chJoroquinc (5-6 mg/kg/day) may n£.-cd to be continued
verrucous (Libman-Sacks) endocarditis. A few autoimmune for several years depending lm thl: clinical response.
diseases may coexist with lupus including autoimmune Infections must be treated aggr~sively with appropriate
thyroid disease, celiac disease and overlap syndromes. antimicrobials and the steroid dO"~ increased during such
epis odes. With appropriate thL-rapy, the Jang-term outlook
Serology of SLE in children is quite t"Jlcouragjng.
Almost all patients with SLE have demonstrable ANA.
Presence of anti-double stranded (anti-ds) DNA antibodies Antlphosphollpld Syndrome
is highly specific of SLE and us.u ally correlate ~ith disease
Antiphospholipid syndrome is a common accompaniment
activity. Anti-histone antibodies are .present m n~o~atal
of SLE but can be seen in association with other
lupus especially those as~ocia ted. wit~ characteristic ?f rheumatological disorders as well. The synd rome can, at
drug-induced lupus. Anh-Ro antlb?dies a~e present. m times, arise de nova when it is known as primary
neonatal lupus especially those associated with congemtal antiphospholipid synd rome. It is a common cause of
heart block. Anti-Sm antibodies are a marker for CNS acquired hypcrcoagulable statc-s in children and is manifest
lupus. with venous and arterial thrombosis, Hvedo reticularis and
thrombocytopenia . The presentation is som e times
Treatment catastrophic and may result in fatality. Laboratory diagnosis
Glucocorticoids and hydroxychloroquine form the is suggested by a typical coagulation profile (normal
mainstay of therapy. Prednisolone is started at doses of prothrombin and prolonged partial thromboplastin times)
1-2 mg/kg/ day and gradually. t~pered o~~r several and confirmed by detection of anticardiolipin anfibodies
months according to disease activity. Arthritis usually (lgM and JgG), anti-132 glycoproteinl antibodies (lgi'vf and
responds to NSAIDs. Sunscreen lotions (with sun IgG) and the lupus anticoagulant test Treatment is with
protection factor of 15-20) must be prescribed for all long-term oral anticoagula tion.
children with lupus and applied 3-4 times/day, even on
cloudy days. . . JUVENILE DERMATOMYOSITIS
Life-threatening comphcahons (e.g. class. IV lupus
nephritis mycocarditis, encephalopathy) reqmre the use Juvenile dermatomyositis (JDM) is not merely a disorder
of intrav~nous pulses of methylprednisolone (30 ~g/kg/ of muscle and skin, but a multisystem disease
day) for 3-5 days. Rituximab, a monoclonal antibody to characterized by nonsuppurative inflammation of striated
CD20, has also been found to be effective in such situations. muscle and skin, and systemic vasculopathy. Unlike
.I
Essential Pediatrics
626 I ~--~~~~----====~~=-----~~~~~~--
- ~ ';'me p0}TinY~--ilis (Le. ii."it.11 no accompanying skin iv. Chemically induced scleroderma (e.g. with polyvinyl
f:ii,·c~~~} is"m-~ in children.. The diagnosis of chloride, pentazocine, bleomycin)
JD~f an be maC.e on basi..s of the f:ollowing criteria: v. Pseudosclerodermas (e.g. phenylketonuria, sclere-
L Chal:-.:.rte-isfu: ~discoloration oYer the upper dema, progeria and porphyria cutanea tarda)
e-re•rls (Fig. 22..22) or a scaly, eryt:hematous rash over Diffuse cutaneous systemic scleroderma is usually
~.J a.c;pecis of metara.rpophalangeal and proximal associated \Vith widespread visceral involvement
mte:p~ezl }oIDt5 (Gottron papules; Fig. 222b) including the gastrointestinal tract, heart, lungs and
ii 5)nur.emca1 proximal muscle weakness kidneys. It is believed that fe~omaternal gra~t-versu~
ill. fl~1.ated ?.e-.-els -of musc1£ enzymes (creatine kinase, host reactions are involved m pa thogenes1s of this
a!aru...'le and 0-partate aminotransferases aldolase) condition. Onset of disease is insidious and may be
difficult to recognize in initial stages. The child presents
h-. .E!a:tromyographic e>idence of myopathy
v.rith skin tightening (edema, atrophy and acrosclerosis),
..-. Muscle biopsy shm••ing myonecrosis, myophago- Raynaud phenomenon (i.e. blanching, cyano~is and
c;,·tosis and perifascicular atrophy erythema), soft tissue contrach.~res,_ arthralgias and
A definite dizgnosis of JDM can be made, if a child myalgias, dysphagia (regurg1tati~n, refl~x a_nd
fulfils the first criterion along \,·ith any three of the aspiration), dyspnea (interstitial fibrosis, low .d.1fh~smg
remajning four and it is considered probable if two of the capacity) and characteristic subcutan~~us calc1f1c~hons.
four criteria are met. Other dermatological changes Many children have abnormalities of nailfold
include edema o..-er eyelids, photosensitivity, truncal capillaries, which can be seen as capillary dropouts and
rash and c.alcinosis. ~!agnetic resonance imaging (J..00) dilated loops with a nail-bed capillaroscope or +40 lens
shows characteristic hyperintense signals on T2- of an ophthalmoscope. Onset of hypertension and
weighted images suggesth-e of muscle edema and proteinuria usually indicates renal involvement, and
inflammation .,.,•hile Tl ·weighted images may show should be a cause for concern.
fibrosis, atrophy and fatty infiltration. Muscle biopsy is
Im·estigations show presence of ANA (with nucleolar
rarely required for diagnosis.
pattern on immunofluorescence) and antibodies to Scl70
Treatment is with pulse .intravenous methylpred.nisolone (DNA-topoisomerasel) or centromere. No form of drug
(30 mg/kg/day) for 3-5 days followed by gradually therapy is curative. Penicillamine and colchicine can
tapering doses of oral prednisolone (1.5-2 mg/kg/day). produce beneficial results in some patients, especially if
Weekly methotrexate (15-25 mg/m:?/week given used early in the course of disease. Monthly pulses of IV
subcutaneously or orally) is the mainstay of maintenance cyclophosphamide (followed by maintenance d aily
therapy. Usual duration of therapy is 18-24 months. Rapid azathioprine or weekly methotrexate) can be life saving
tapering of steroids may result in disease relapse. Long- in patients with interstitial lung disease. Nifedipine is
term prognosis is excellent, if treatment is started early.
useful for management of Raynaud phenomenon while
enalapril can result in control of blood pressure and
SCLERODERMA stablization of renal function. The latter is also the drug
Scleroderma refers to hardening of the skin. It can be of choice for scleroderma renal crises. With appropriGte
classified as follows: management, 10 years survival rates of up to 90% hu.ve
L Systemic scleroderma (e.g. diffuse cutaneous, limited been reported in children.
cutaneous) Scleredenza is a benign, self-limiting condition
ii. Overlap syndromes characterized by non-pitting indurated edema over face,
iiL Localized scleroderma (e.g. morphea, linear sclero- neck, shoulders and chest, but excluding the hands and
derma, eosinophilic fasciitis) feet.
of involvement: TYJI<' I: Aortic arch; 7)//'t' ti: DesCl'lHling c rythcma o{ hanJu or (1!1:1; c11nv<1lc'>Cent ~ ta~c:
dt~Atfllillllillion, whkh uiiually b1·gln11 p1:TiUnJSWlllyJ
aorta; Type III: Aortic arch and descending nmla; 'f!J/h' /V:
Aorta and pulmonary nrtcry. Children with TnknynAu Iv. 1'0/y11wrr1lw1trJ rati/1 (rn:vcr vc1;lc:ul;n)
arteritis often show a strongly positive tuberculin rcncllon. v. Ct'rvlcnl lympltndenopr1/hy (at lca•,l I node 21.5 cm;
The classification criteria for childhood Tnknynsu nrtcrlliA uHually unilall!ral)
are given in Table 22.5. C. lllncAA not explained by any other known diwa~c
Diagnosis is confirmed by nngiogrnphy. Treatment process.
involves long-tem1 inmmnosuppression with prednlsolonc These cllnlcill fcalureHevolve 6<!q uc:nlially uvc.-r a pc.'t'iod
and methotrexate (used in weekly doses). Mycophenolnte of dayi; anti all need not be prc1>1:nl loh ·!her at a given
mofetil has also been found to be useful. Angioplnsty point or lime. This partly cxplaini. tht: difficulty that the
procedures are now being increasingly performed even clinician experiencei; in arriving al ;J t iirrcct diagn O"~i;.
in small children and show promising results. Most children have high grade fever and arc extrc:mdy
Cyclophosphamide or azathioprine mny be required in irritable. Jn fact il i!> !hi!; irritabi lity that often prnvide-., the
children who foil to show nn adequate response to steroids. first clinlcnl clue lo Jiagnoi;i~. Other chM;ictr:ri'llic clinical
Hypertension must be managed appropriately. finding,; include pcrianal dc11quamation (in fir~t fcw day!>
of fever) anu reactivation of BCG i;car, uc,uai ly !>cen in
Kawasaki Disease infanlR). Arthritis is ofll'n sc1:n in childrl'n wi th Kawasaki
Kawasaki disease is an acute febrile mucocutnneous disease nnd mny rl.'sull in diagnostic confu.,i!Jn. Hydrops
lymph node syndrome mainly <1ffecting in fonts nnd young of gall bladder can abo occur. Sterile pyuria is common
children. More than 80% of cnses nre seen in chilurcn nnd, in the setting of ongoing fcvl.'r, may lead to an
under 5. It is the commonest vasculitic di sorder of erroneous diagnosis of urinary tract infection.
childhood and has replaced acute rheumatic fever as the KD must be considered in differential diagnosis of all
leading cause of acquired heart disease in children in many children, especially lholie below 5· ycar·old, who have
countries. The basic lesion is a necrotizing vasculilis of £ever without apparent focus lasting more than 5 days.
Thrombocytosis with periunt;ual peeling i.s characteristic
·Table 22.s: c1a5siflcat1on criteria for childhood Takayasu arterltls of second week of illness. 13t•au lint's may be seen during
Angiographlc abno;malltle; (conventional, CT or MRI) of the the convalescent phase (Fig. 22.4).
aorta or Its main branches, plus at least one of the following 4 Treatment is with a single dose of intravenous immuno-
features: globulin (2 g/kg) and aspirin in anti-infl.:immatory doses
Decreased peripheral artery pulse(s) and/or claudlcatlon (30-50 mg/ kg) until the chil<.l bccom,•s a febrile. Low dose
of extremities aspirin (:\- 5 mg/kg/ d ny) is then continued fur 4-6 weeks
Blood pressure difference between both limbs >10 mm Hg for ilH anliplalclet activity . In appropriately treated
Bruits over aorta and/or Its major branches children, lhe lung·lerm prognosis is excellent with less
than 3'Y., palicnl::1 developing coronary artery abnormalitic.'S
Hypertension
ns compared to 15-2S'Y,, in the unlrc<1tcd category.
- 628 I Essontlol Podlotrlce
Fig. 22.3: Findings in acute phase of Kawasaki disease. (a) Red cracked lips; (b) Strawberry tongue; (c) Swelling on dorsurn 0f
hands; and (d) Perlungual d esquamatlon.
Fig. 22.5: Findings in polyarteritis nodosa Include (a) Livedo reticularls; and (b) Microaneurysm (black arrow) on angiography
'Table 22.6: Classification criteria for childhood polyarteritis Table 22.7: Classification criteria for childhood Hcnoch·
nodosa SchOnlein purpura
A childhood illness characterized by the presence of either a Palpable purpura with at least one of the following:
biopsy showing small and mid-size artery necrotizing vasculitis
Diffuse abdominal pain
or angiographic abnormalities (aneurysms or occlusions),• plus
at least 2 of the following: Any biopsy showing predominant lgA deposition
Arthritis or arthralgia
Skin involvement
Renal involvement (any hematuria and/or proteinuria)
Myalgia or muscle tenderness
Systemic hypertension CNS vasculitis, coma, Guillain-Barre syndrome,
Abnormal urinalysis and/or impaired renal function pulmonary hemorrhage, carditis and orchitis.
Mononeuropathy or polyneuropathy
Testicular pain or tenderness Laboratory Investigations
Signs or symptoms suggesting vasculitis of any other major IgA vasculitis is a clinicnl diagnosis and none of the
organ systems (gastrointestinal, cardiac, pulmo- laboratory features are pathognomonic. There may be a
nary or central nervous system) nonspecific increase in total scrum IgA levels. Many
'Should include conventional angiography if magnetic resonance children may ha ve microscopic hematuria and
angiography is negative proteinuria. Skin biopsy from the involved sites shows
leukocytoclastic vasculitis. On indirect immuno-
the first few days of illness. Glomemlonephritis is seen in fluorescence, there arc deposits of lgA in skin as well as
approximately one-third, but only 10% patients have renal biopsies. Ultrasound examinations may need to be
azotemia or nephrotic range proteinuria. Clinically, it may repeated for evolving abdominal findings.
manifest as isolated hematuria, hypertension or a
nephritic/nephrotic syndrome. Significant renal Treatment
involvement is uncommon in children below 6 years old. Management is generally supportive with maintenance
Gastrointestinal manifestations usually occur in first of hydration and pain relief. Prcdnisolone (1-1.5 mg/kg/
7-10 days of the illness. Affected children may be erroneously day) is often given in children with gastrointestinal
diagnosed as having a 'surgical abdomen'. Abdominal involvement and is usually continued for 2-3 weeks (in
pain is usually intermittent, colicky and periumbilical. gradually tapering doses) depending on the clinical
Vomiting occurs in about 60% of patients but hematemesis response . There is, however, no clear evidence that
and malena are relatively less common. Intussusception steroids alter the natural course of disease.
(ileoileal or ileocolic) can be seen in the acute phase. Nephritis due to IgA vasculitis may need aggressive
Most clinical features of IgA vasculitis are self-limiting management with immunosupprcssants (prcdnisolone
and resolve in a few days. Rare manifestations include and azathioprine).
- 630
B h et disease is characterized by multiple relapses
Prognosis .the ! if"cant disability from ocular and neurological
The disease usually runs its entire course in 4 weeks and wi sign i . (
mam"fes t a ti·ons · Widespread thrombosis
. venous
. and
majority of children have no permanent seq~el~e. even arterial) of large vessels may be life-threaterung. Many
when the short-term morbidity is quite significant. patients show a positive pather~ test (cutaneous pustular
Children older than 6 years with significant renal . following needle pricks). HLABS and BS!
involvement (especially children with rapidly reac t10n . h h" d
h ap10 typ have been associated
es wit t is syn rorne.
progressive glomerulonephritis and crescents) nee.d ~o Dru therapy involves use of cokhi cine· an d thal"d ·
1 onude.
be closely followed up; the long-term pr?gnos1s. is Me~otrexate and chlorambucil have also been used.
guarded in such situations. Overall 1-5% of children with
nephritis due to IgA vasculitis progress to end stage renal Suggested Reading
disease. • Ozen s, Ruperto N, Dillon MJ, Bagga A, ~amorz K, Dav~ JC'. et al.
EULAR/PRES endorsed consensus critena for the classification of
Granulomatosls with Polyangiitis ('Negener granulomatosis) hildhood vasculitis. Ann Rheum Dis 2006; 65:936-41.
• ~etri M Orbai AM, Alarc6n GS, Gordon C, Merrill JT, Fortin PR,
This condition is characterized by necrotizing granulo- et al. o:rivation and validation of the Systemic Lupus Inter_national
matous angiitis affecting the respiratory tract and kidneys. Collaborating Clinics classifica tion criteria for systemic lupus
It is rare in children. Constitutional symptoms are quite erythematosus. Arthritis Rheum. 2012; 64:2677-86.
prominent. Presence of anti-neutrophil cytoplasmic • Singh S, Abujam B, Gupta A, Suri D, Raw at A, Saikia B, et al.
antibodies (ANCAs), especially c-ANCA, are virtually Childhood lupus nephritis in a developing country-24 years' single-
pathognomonic. With steroids and cyclophosphamide and center experience from North India. Lupus. 2015; 24:641-7.
• Singh S, Chandrakasan S, Ahluwalia J, S~ri ~' Rawa~ A, Ahme.d
occasionally, intravenous immunoglobulin, the long-term N, et al. Macrophage activation syndrome rn children with systemic
outlook is satisfactory. onset juvenile idiopathic arthritis: clinical e xperience from
northwest India. Rheumatology International 2012; 32:881-886.
Behc;et Disease • Singh S, Newburger J, Kuijpers T, Burgner D. Management of
Kawasaki Disease in resource limited setting. Pediatric Infectious
This is an extremely uncommon vasculitic disorder, with Disease Journal 2015; 34:94-6.
variable clinical manifestations. • Singh S, Suri D, Aulakh R, Gupta A, Rawat A, Kumar RM. Mortality
i. Major: Aphthous stoma titis, genital ulceration, in children w ith juvenile dermatomyositis : two d ecades of
cutaneous manifestations and ocular disease experience from a single tertiary care centre in North India. Clin
Rheumatol. 2014; 33:167S-9.
ii. Minor: Gastrointestinal disease, thrombophlebitis, • Singh S, Vignesh P, Burgner D. The epidemiology of Kawasaki
arthritis, family history and neurological involvement. disease: A global update. Arch Dis Child. 2015; 100:1084-8.
Chapter
23
Genetic Disorders
Neerja Gupta • Madhulika Kabra
.I
•
I
I
I
Fig. 23.1 : Schematic structure of a chromosome Fig. 23.2: Concept of locus, gene, allele and genotype
631
Essential Ped•atr•cs
c:E:.£:5:-n a-::sep.~·\found d1:::.turom..~ in thl' £~'\l'tk •WC ,)bscrvcd in the same individual. If the nondisjunction
''" ,......-- -;:n ro:re-~:-:-~21-:id~""t i~SUT\i\",\l. Dl'pendit\g occurs ,,ft-er a fow mitotic divisions have already occurred,
~ro ~ ~ ci <Il...~;:)J.-m;ilit\-. the cim.'lm~'\11'\l' im·uh't.'i mo~ th;m two cell lines arc observed, some with normal
.::;c 62~ci::i'-uhne'i',, thmnuy ~an '-"1rly ~'1'l1'rtion, llth.i ,)thcrs with abnormal complement of chromosomes.
seJ. ti.....21. .:r.ea:-.!.~ .:3.:-.:.fu. m2lformations or in~lkx:hl•ll
Structural Ct1romosome Abnormalities
~"-£.:.._._ ...\: ~ O!'Jy ·.3 pm ()t thl' cl\romo..~l",me may
red=-...J::i"-.ri".3 m )~ c.::.us:n_g )~ $C\'e.t~ ~ctk distun\.lt'\~S. Olief types of structural chromosome abnormalities are:
~ 2..Dy. ~~ ,c i .3 wh01e chromosome, except the (i) translocation, (ii) inversion, (iii) deletion, (iv) duplica-
:<C!:ro!:Jcs...""O~ 1.::s :n Tu..."Tier ~"Tldnm1e) , is lt-thal. Sun·eys tion, (v) ring chromosome and (vi) isochromosomes.
a 5iill-~~ rr ...b.._-u-tu.~ ~ow chrom~mal anom,\li~s
TriU1$lt>catio11 (Fig. 23.5): A chromosome or segment of a
b. a .a..~e ~~"\!-Sun.. flye .."'It lOC\1 liw newboms, h~we chromosome may break off from the parent chromosome
~~zn..~- ~are t-,,-~"' ty~of clm.'lmCl$0m:tl
,rnd j\)tn another chromosome, in a process called
~~~1umeriral (a...•euploidies) and structur~l.
tmnslocation. One chromosome may appear shortened in
~~~d.~ re:,.-ult fn."Un failure of chromosomes to
this process. If no loss or gain of the genetic material
~~during rell dhision. This phenomenon
occurs, the translocation is balanced and the person is
is knm..-n as m:mdisjunction. Nondisjunction during phenotypkally nonnal. Translocated chromosome may be
~-is I !82.ds to furmatian of disomic or nullisomic
transmitted to either gamete during meiosis, such that
gamehs, resultin~ _. in tri..'Llmic and monosomic zY•:!Ores
... b , when it mates with a normal gamete, the resulting zygote
respec:trrely; ncmdb"junction during meio5is 11 results in may have either excess or deficiency of the genetic
monosomic, di.--omk and nulli..<:-0mic gametes, leading to material. Such an offspring is abnormal. Viability of such
disomic (~ drrmnosomes}, trL.;;omic (-17 chromosomes) and
zygotes would depend on the essentiality of the genes
~ p:; chromosomes) zygotes, respectiYely, as
carried on translocated portion of the chromosome.
shown in Fig. -,:;3_ ~ondi..9unction may occur in maternal
or paternal germ cells, but is more common in the f-om1er D_clctia11 (Fig. 23.6): A segment of chromosome may break
and with increasing age. Common aneuploidies in live otf and be lost. Loss of a portion of chromosomal material
born babies include Down syndrome (trisomy 21), Edward large enough to be seen by light microscope is often lethal
syndrome (trisomy 18), Patau syndrome (trisomy 13, or poorly tolerated. Gene deletion syndromes are
Fig. 23.4) and Turner syndrome (monosomy X'). characterized by loss of a cluster of genes, giving rise to a
n Gamete
Gametes
Fertilization//
/
/
C
·n, :
l~ \\ ' l- ,
I
I
I Fertilization
/
\ I ' I
~·
CD,~. (()
' , ....._ I
Monosomy Trisomy
II IJ
4 5
IJ Cl II
_1_0_ - - 1 1 - 1 2
_JI__
16
I! 11
-1-7- --18-
II19 Bl
20 21 22
_I _1
x y
Interstitial deletion Terminal deletion
0
Fig. 23.4: Aneuploidy of chromosome 13 (trisomy 13)
U IJ H ~- --3
5
1i Ii aa
6 -7- - II I~ =~ ~~
8 - - - 9 - __1_0___1_1___1_2_
Q
a~
-1-3- ee
--1-4- e&
__1_5_ 31 Si
--16- --17- --1-8
Translocation
I •
-2
1
~ I& (Is
~
tifil
@-y
a
Fig. 23.6: (a) Schematic diagram of deletion; (b) Karyotype
H@ii
with deletion of long a rm of X chromosome
3
ii 4 5
of parathyroid and thymus, facial and palate anomalies;
22qll). Submicroscopic deletions are detected on special
if II JJ »M J' 1»~2
chromosomal staining or fluorescent in situ hybridization
it -=r
-6- - 8 - - 9- _ 1_0_ - -1-1-
(FISH) (Fig. 23.7). DNA probes make it possible for FISH
to be used for diagnosis for aneuploidies and micro-
«•
-13-14'~
!ft ftd
deletion syndromes.
~K I -v
-x- D
19
b
Fig. 23.5: Translocation. (a) Cartoon indicating exchange of
parts of chromosomes. (b) Karyotype showing translocatlon
between chromosomes 2 and 20 (t[2;20)]
Dr1plications are abnormal duplication or copy of part of on maternal side or inheritance of both copies frorn
a particular chromosome that result in extra genetic paternal side).
material. Chromosomal abnormalities are generally sporadic and
therefore, the risk of their recurrence in offsprings is low,
Ring chromosome (Fig. 23 .8) occurs due to a two except when either parent is carrying a balanced trans.
breakpoint event involving the ends of the p and q arm
location.
which leaves two sticky chromosomal ends that join to
form a ring.
Testing for Chromosomal Disorders
Inversion (Fig. 23.9a) results from one or two breaks along Laboratory testing for chromosomal disorders includes
the length of the chromosome arm. The broken pieces conventional karyotyping, fluorescent in situ hybridization
rotate by 180 degrees and reinsert in a novel way. If there (FISH), quantitative PCR (qPCR), multiplex ligation probe
is no loss or gain of genetic material, there may be no amplification (MLPA) and chromosomal microarray
significant clinical manifestations. Break point is important
(CMA).
if it disrupts a vital gene.
The process of making chromosome preparations by
Isochromosome (Fig.23.9b). During mitotic cell division, in vitro culture, staining, identification and classification
the chromosome divides longitudinally. Rarely it divides of chromosomes is called karyotyping. Karyotyping can
transversely across the centromere, with half of the be performed on peripheral blood lymphocytes, bone
chromosome replicating to form its complement. Thus marrow aspirate and tissue biopsy material. The process
instead of normal chromosomes, two new types of is labor intensive and involves culture, followed by
chromosomes are formed, one having both the long arms harvesting chromosomes after the cells are arrested in
and the other with both the short arms. These are known mitosis. After preparation of slides, staining (usually
as isochromosomes. Each isochromosome has excess of Giemsa stain) is done to produce a banding pattern unique
some genetic material and deficiency of other genetic for each chromosome (Fig. 23.10). This enables detection
material. For example, isochromosomes cause some cases of numerical and structural abnormalities through the
of Turner syndrome. genome at a resolution of approximately 5 Mb. The
Genomic imprinting: Maternal and paternal sets of genes chromosomes from one metaphase figure (a single cell)
are not always functionally equal. Some genes are are classified according to their length (chromosome one
preferentially expressed from maternal or paternal side. is the longest) and banding features into groups called a
Examples include Prader-Willi syndrome (microdeletion karyotype.
on paternal side or inheritance of both copies from Molecular cytogenetic techniques include FISH,
maternal side) and Angelman syndrome (microdeletion quantitative polymerase chain reaction (qPCR) and
•
le (1 2
Cl3
it («
4 5
BJ
6
le 6< «»
7 8 9
1)
10
II
11
I»
12
I
~
AG
13
It
14
66
15
ca
16
II
17
no_
18
a b
,.
19
II
20 "'
21
IA
22
I
x
,_
y
Fig. 23.8: (a) Schematic representation; and (b) Karyotype showing ring chromosome 18 in a child with developmental delay and
seizures (see red arrow)
1
cC!"f-
Genetic Disorders j 635 -
- cc
__ §c~~~
~ ~~ ~ ~~ i~
..... ~c--,._-
8 . ..,_ . .
'l!
~
"~-
'E~ ~~~ h.....
c:
c:
:;i .G c: -
lfl~~
.. . a
:: ~ 2 --n . ;.,:o ~:;; ,.,
~::i~.
N
";~
:,,.,.: ::< ;:...=..~--
::-a;a; :i: '-: !i. ..,;:d.,l
3.5
-r "? ":" ...~ ~
o =-·
~~
. .. ~~
: ;, g,
'I' Q cD ~ i::f : :
~
~;_.:,, '7'1'
~~ ~ :r c;; 8~ ~:i:C~=H
II)
CD N
· 2~
... ... ...
uu u
::12::1
~
~
~
0;:
... zu
<-
... c. ~3~~5U s
li! w
)(-.._er-
--:--r
Cl.ZZ
~~
"-z
OUJ
ii'~'.)
~~~
NN
~~
~
w
II)
oz3
~ uj w
3
2.5
1.5
0.5
Rg. 23.1 O: MLPA analysis showing hemlzygous deletion (Indicated In red) In a patient with Smlth-Magneis syndrome
"'"'~
21
(imnnthri o( ''W, .111d llwn tivury YtJM,
Tliyl'lllil ily.~.fl11lft/0111 Ahn111 I ~ -!lil,°Yi, JMllu11 lq wllh I).,.1111
symlrom11 h1W•' hypn1hyroldi11111 . l hyn1ld (1 11 1• 111111 t"'"'-
(T~ ,rnd TSI I) .ir11 n 11·n111111u111l"d unru in llw 111:1111111 ~ 1
pllrlnd or 111 flrr1 I ro11l 1wl, 1•vu1·y ttl11 r111111lht1 in lllf1111• y 11/l•j
llwn ovtiry yi•11r. 'I hlH Hlt1111ld ld1•1illy l111fodll 1111 t)ll1y11 1j. j
1mtllmdh)tl, ut1p1•dr1ll y 111 oldur chll1lr11n, 11~ 11ll1;J11~y lb
.. l1Sll1llly 11\lllllJlll\1111111,
1\tl1111t11-111·1'/11//11/ t111f1l1m1f/11111 'f litt l11t'ld1•11f1! lei Ynll11l1J1:1
1·cporl1•d 111 lll·-'.'HI%. l.11l1 1 r1il 11uck t'r1cl l11v,f1qiJ1 1~
e•/ .. . recomnwrnl1•d onrn 111 :l- ~ yt•a1·,,, lwf11r11 "'"'Pi" ry, (11 1
pMlld p1lllnn 111 hp11rl1ll g.11111'11, •II' t•r1rl l11r, it ::ifv,11., n1a.J
"
Ag. 23.11: Three types of chromosomal abnormalllles found 21 '
" " Iii
- !. .·~· 1._· - ..
Fig. 23. 12: Children with Down syndrome at (a) 3 months; (b) 15 months; and (c) 2 yoars ol a~Jl). Noto tho flat t~c l<n, ufi'll0 1rJttl''
slant and open mouth appearance
Genetic Disorders
j 637 -
Table 23.1: Evalu~tlon In patients with Down syndrome
E'vt1lt111tlon
Frequency of assessment
Growth
Twice a year in first year; annually till 5 years
Auditory (screen for hearing loss, otltls media)
Oculnr
Thyroid profile
Cardiac evaluation
At Initial contact; follow up if congenital heart disease
Hematology
Screen for leukemia, twice a year in first year; monitor as
per need
Dental
Annually
Additional evaluations
Routine Immunization as per schedule
Vlgllance about signs of gastroeso h 1 fl d' · · ·
Early stimulation therapy p agea re ux isease, cellac disease, obstructive sleep apnea, atlantoaxial dislocation
Physiotherapy, occupational and speech therapy
Guidance regarding vocational training, hygiene and self-care
Discuss behavioral Issues
Counseling regarding future pregnancies and prenatal diagnosis
Counsellng
Options for couples who come late or opt for initial
I
Parents of a child with Down syndrome should be screening with serum markers and ultrasonography are
counseled wit~ tact, compassion and truthfulness. Briefy, karyotyping by amniocentesis at 16-18 weeks, trans-
one ~hould : (1) Inform about the disorder as early as abdominal chorionic villus sampling and cordocentesis
possible after diagnosis is confirmed; (ii) counsel in after 18 weeks. Karyotype results are available within a
presence of both the parents in privacy; (iii) talk in simple week wi~ cord blood samples and direct chorionic biopsy
and positive language giving hope and allow sufficient preparations. The results of amniotic fluid cultures take
time to the parents to ask questions; (iv) discuss known about two weeks. Rapid testing using FISH and
problems and associated disorders; (v) highlight the quantitative PCR is very reliable and results are available
importance of early stimulation; (vi) not discuss in 24-48 hours.
institutionalization and adoption, unless asked, and
discourage both the options; (vii) ask parents to contact TURNER SYNDROME
the local Down syndrome association, if one exists; Turner syndrome, with 45 X chromosomal constitution
(viii) talk about genetics only after chromosomal analysis; has an incidence of -1 :3000 newborns. However:
(ix) inform about recurrence risks and possibilities of chromosomal studies of spontaneous abortions have
prenatal diagnosis; and (x) schedule future appointments. clearly shown that majority of 45 X fetuses are likely to be
Risk of recurrence: Women 35 years of age or less who aborted. Since there is no apparent relationship to
have a child with trisomy 21 have a 1% risk of having advanced maternal age, it is likely that the condition does
another, which is significantly greater than the general not arise from gametic nondisjunction.
population. The risk is little increased, if any, over the Cytogenetlcs
usual maternal age dependent frequency if the mother at
risk is 35 years or older. For translocations inherited from Many patients with Turner syndrome show considerable
the mother, the risk is about 10%, whereas it is about degree of chromosomal mosaicism, i.e. 45, XI 46, XX: or
4-5% when father is the carrier. Balanced translocation other karyotypes with multiple cell lines. Formation of
21; 21 is the only situation where all viable fetuses will isochromosome of long arms of X chromosome may lead
have Down syndrome. to Turner phenotype with 46 chromosomes because of
absence of short arms. Figure 23.6b shows a karyotype of
Prenatal screening and diagnosis (also section: Prevention a child with Turner syndrome ,..,,ith deletion of long arm
of Genetic Disorders). Parents who wish to get a prenatal of X chromosome
diagnosis have a number of options. They can directly get
a fetal karyotype either by chorionic villus sampling (by Clinical Features
transcervical or transabdominal route) or amniocentesis. Turner syndrome may be recognizable at birth.
Alternatively (if the parents do not want invasive testing) Lymphedema of the dorsum of hands and feet and loose
an initial screening may be performed with maternal skin folds at the nape of neck may be present. Other
serum markers and ultrasonography (as discussed later). manifestations include short stature, short neck with
- s3a 1 Essential Pediatrics
Management
Height monitoring should be done using growth charts for
Turner syndrome. Cardiac evaluation and measurement of
blood pressure is reconunended at baseline and every year.
Ag. 23.13: Turner syndrome. Note (a) ?tosls In right eye, shield Treatment with growth hormone is reconunended. While
chest. Increased carrying angle, webbed neck and short neck; therapy may increase the final height by 8-10 cm, the cost
and (b) low posterior hair llne
is prohibitive. Thyroid testing should be done in infancy
'"·ebbing and low posterior hair line. Anomalous ears, or early childhood, if the child is lagging in growth. Routine
prominent narrow and high arched palate, small mandible evaluation is required after 10 years of age. Counseling
and epicanthic folds may be noted. Chest is broad shield- regarding behavioral problems due to short stature,
like with widely spaced hypoplastic nipples (Fig. 23.13a amenorrhea and sterility is an integral part of management.
and b). There is increased carrying angle at elbow. Bony Ovarian hormone replacement is advised around 14 years.
anomalies include medial tibial exostosis, and short fourth Conjugated estrogen (0.3 mg/ day) or ethinyl estradiol (5-
metacarpals and metatarsals. Pigmented nevi may appear 10 ug/ day) are given for 3-6 months; the dose of
in older patients. At puberty, sexual maturation fails to medications may be increased. After 6-12 months, cyclical
occur. The phenotype is highly variable. It has been therapy with estrogen and progesterone is started.
recommended that the diagnosis of Turner syndrome Regular audiometry is advised in adulthood or earlier,
should be considered in all girls with short stature. if indicated. Evaluation for renal malformation by ultra-
Ultrasound may show streak ovaries and hypoplastic sonography should be done at first contact. Prophylactic
uterus. Levels of FSH and LH are increased (hyper- gonadectomy is advised for patients with Y chromosome
gonadotropic hypogonadism). Adult stature is usually due to the risk of developing gonadoblastoma.
below 145 an. Associated congenital defects are common Table 23.2 gives brief description of some common
in kidneys (horseshoe kidney, double or cleft renal pelvis), aneuploides.
Table 23.2: Clinical features of common aneupioidies
Aneuploidy Clinical features Management
Trisomy 18 Failure to thrive, developmental retardation, hypertonia, micro- Symptomatic, supportive
Edward syndrome gnathia (Fig. 23.14a), shield-shaped chest, short sternum, joint
abnormalities including flexion deformity of fingers (Fig. 23.14b and c),
limited hip abduction and short dorsiflexed hallux. Congenital heart
disease is common
Trisomy 13 Development and physical retardation, microcephaly, sloping Symptomatic, supportive
Patau syndrome forehead; cleft lip with/without cleft palate common
Holo·prosencephaly; varying degree of incomplete development
of forebrain, olfactory and optic nerves
Microphthalmia, iris coloboma, retinal dysplasia and cataract; deafness
Capillary hemangiomata (Fig. 23.15); polydactyly, flexion deformities
Congenital heart disease (80%); most die by 6 months of life
Klinefelter syndrome Hypergonadotropic hypogonadism, small testes, fail to develop Behavioral and psychosocial
47,XXY secondary sex characters; tall stature, gynecomastia rehabilitation
Borderline intellectual disability, behavioral problems Testosterone therapy in middle·
Consider diagnosis in boys with mental retardation, psychosocial or late adolescence
learning disability, or problems in school adjustment
Genetic Disorders
I 639 •
I
PREVENTION OF GENETIC DISORDERS
bleeding in cases of hemophilia. Enzyme replacement
therapy, although expensive, has become feasible with the Carrier Screening
availability of deficient enzymes for Gaucher disease, It is now possible to detect the carrier state in a large
Hurler syndrome, Hunter syndrome, mucopoly- number of autosomal recessive or X-linked recessive
saccharidosis type VI, Fabry disease, MPS IV and Pompe disorders. HbA2 levels are highly useful in identifying
disease. carriers of thalassemia trait pre-pregnancy or early in
Promoting excretion of toxic substances: The excretion of pregnancy. In India ideally all partners should be tested
certain metabolites can be promoted by chelating agents, for beta-thalassemia carrier status as the condition is very
e.g. penicillamine promotes excretion of copper in patients common in North India. Female carriers of Duchenne
with Wilson disease and desferrioxamine is used to chelate muscular dystrophy may show high serum levels of the
iron in patients with thalassemia and hemochromatosis. enzyme creatinine phosphokinase, but can be tested more
precisely using molecular techniques. Such techniques are
Augmenting enzymes: Certain enzyme systems, which increasingly used for detection of individuals who are
may be immature or reduced at certain phases of life may likely to give birth to offspring with hereditary disorders.
be induced or stabilized by the use of chemical agents.
Phcnobarbitone is used to induce hepatic microsomal Newborn Screening
enzymes Jike glucuronyl transferase in cases of neonatal
hyperbilirubinemia or Crigler-Najjar syndrome. In some This is an example of secondary prevention by early
metabolic disorders, enzymatic block can be bypassed by diagnosis and treatment. Newborn infants are screened
administration of large quantities of the coenzyme, e.g. routinely for some endocrine disorders and inborn errors
pyridoxine in homocystinuria. of metabolism in developed countries. This is of special
value for detecting affected cases in the newborn period,
Avoid precipitating factors and drugs: Certain drugs, so that handicap can be prevented or minimized by early
which precipitate adverse symptoms in metabolic treatment, e.g. congenital hypothyroidism, congenital
disorders, such as barbiturates in porphyria and oxidating adrenal hyperplasia, phenylketonuria, galactosemia and
agents in glucose-6-phosphate dehydrogenase deficiency, tyrosinemia.
should not be given to affected patients.
Stem cell transplantation is recommended for many Prevention of Neural Tube Defects
genetic disorders like thalassemia major, severe Hurler Folic acid supplementation is recommended at a dose of
syndrome and some primary immunodeficiencies. 0.4 mg daily from 1 month before to 3 months after
Surgery helps to reduce the functional or cosmetic conception to prevent neural tube defects. Expectant
disability in some structural defects, e.g. removing the mothers at high-risk of such defects (e.g. previous fetus
spleen in hereditary spherocytosis. Solid organ transplan- with neural tube defects) should consume 4 mg of folic
tation, of liver, kidney and heart, is available across India. acid daily to prevent recurrence.
Conditions where transplantation may be useful include
ornithine transcarbamy1ase deficiency, maple syrup urine Maternal Serum Screening
disease, cardiomyopathies and polycystic kidney disease. Estimation of pregnancy associated plasma protein A
Supportive care: Patients with hemophilia and osteogenesis (PAPP-A) and free human chorionic gonadotropin (hCG)
imperfecta should be protected from trauma and other in the first trimester and serum alpha-fetoprotein, hCG,
Genetic Disorders I s43 -
unconjugated estriol and inhibin A in second trimester based tests. Single gene disorders, e.g. thalassernia, sickle
are useful biochemical markers to detect aneuploidies. If cell anemia, hemophilia, Duchenne muscular dystrophy
the risk of bearing a child with Down syndrome is more and cystic fibrosis can be diagnosed prenatally.
than 1:250, prenatal fetal karyotyping can be offered. Fetal
ultrasonography helps to detect fetuses at high-risk for Genetic Counseling
chromosomal abnormalities. Findings in the second Genetic counseling is a communication process, which
trimester which suggest Down syndrome are increased deals with problems associated with occurrence and
nuchal fold thickness, short femur and humerus length recurrence of a genetic disorder in a family. It is the process
and duodenal atresia. In the first trimester, nuchal by which patients or relatives are advised of the risk of
translucency and nasal bone are robust markers. transmission, occurrence and consequences of the
Alpha-fetoprotein and estriol are low, whereas hCG is disorder, and how this can be ameliorated or prevented.
high, in pregnancies with Down syndrome fetuses. The Genetic counseling is an important component of
detection rate of Down syndrome by triple test in the management of genetic disorders, since definitive therapy
second trimester is about 65% with a false positive rate of is not available for most cases.
I
5%. All three markers are reduced in fetuses with The objectives of genetic counseling are:
trisomy 18. Ultrasound findings help in counseling, • To provide information about the disease to the
particularly if the parents have opted for initial screening individual and the family
with maternal serum markers. First trimester screening • Help the individual or family to choose a course of
using dual markers has high detection rates, which action that seems appropriate in view of disease risk,
improves further if ultrasound markers are combined. family goals, and ethical and religious standards
Elevated maternal serum alpha-fetoprotein level is a • To make the best possible adjustment to the illness in
sensitive marker for fetuses with open neural tube defects. an affected family member, and risk of recurrence.
Prenatal Diagnosis and Selective Termination of Counseling should be undertaken by a physician with
Affected Fetuses proper understanding of the genetic mechanisms.
Indications for genetic counseling include: (i) Knmvn or
This is a successfully used modality for preventing birth suspected hereditary disease in a patient/ family; (ii) birth
of affected babies and reducing the load of lethal, defects in previous children; (iii) unexplained mental
chronically disabling, untreatable or difficult-to-treat retardation, dysmorphism, multiple malformations;
genetic disorders in the community. Non-invasive (iv) consanguinity; (v) exposure to a teratogen during
prenatal screening (NIPS) is also being used for screening pregnancy; and (vi) identification of malforrnation(s) by
high risk pregnancies for aneuploidies. This NGS-based ultrasonography during pregnancy.
technique evaluates mother's bloo~ for common fe_tal
aneuploidies after 10 weeks of gastahon and has negative Suggested Reading
predictive value of 98-99%. Positive tests would need • Cassidy SB, Allanson JE. Management of genetic syndromes, 3rd
confirmation by invasive testing. edn. Wiley Blackwell, USA, 2010.
• Harper PS. Practical Genetic Counseling, 7th edn. Wright
Invasive Prenatal Testing Publishers, Bristol, 2010.
This includes chorionic villus biopsy (at or after 10-12 • Jamuar SS, Tan EC. Clinical application of next-generation
sequencing for Mendelian diseases. Human Genomics 2015; 9:10.
weeks gestation), amniocentesis (16-20 weeks) and cord
• Miller DT, Adam MP, Aradhya S, et al. Consensus statement:
blood sampling (after 18 weeks). Proce~ure rel_ate? ri~k is
chromosomal microarray is a firs t-tier clinical diagnostic test for
lowest with amniocentesis (-0.5%), wh1le chonoruc villus individuals with developmental disabilities or congenital
biopsy has a risk of fetal loss in about 1%. These samples anomalies. Am J Hum Genet 2010; 86, 749-64.
can be used for chromosomal studies, DNA based tests or • Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis
enzyme assays. Amniotic fluid _is ~e ~refer~ed sample for for noninvasive examination of trisomy. N Engl J Med
chromosomal studies and chonoruc villus tissue for DNA 2015;372:1589-97.
Chapter
24
Inborn Errors of Metabolism
Neerja Gupta • Madhulika Kabra
Inborn errors of metabolism (IEM) are conditions caused with slow progression. They usually have characteristic
by the genetic errors related to synthesis, metabolism, findings that enable a specific clinical diagnosis.
transport or storage of biochemical compounds. The
metabolic error usually results in the accumulation or Clinical Suspicion
deficiency of a specific metabolite. These disorders are The diagnosis of IEM is often delayed, and requires a high
individually rare, but collectively common, and manifest index of suspicion. Symptoms are often nonspecific,
at any time from the fetal life to old age. Early recognition leading to evaluation for other disorders. Clues that
of signs and symptoms, prompt evaluation and suggest the presence of an IEM are listed in Table 24.1.
management results in optimal outcome.
Classification
Table 24.1: Clinical clues suggessting IEM
Intoxication group includes disorders of intermediary
Neonates
metabolism, with accumulation of toxic compounds
resulting in acute or progressive symptoms. Amino- Unexpected deterioration after normal initial period
acidopathies (e.g. phenylketonuria, maple syrup urine Nonspecific, unexplained features such as poor feeding,
disease), organic acidurias, urea cycle defects, disorders lethargy, vomiting, hypotonia, failure to thrive, respiratory
abnormalities, apnea, bradycardia and hypothermia
of carbohydrate and copper metabolism and porphyrias
belong to this category. Symptoms are precipitated by Children
catabolic state (fever, infections, immunization, Sudden a.nd ra~id illness in a previously well child precipitated
dehydration or fasting). by fever, infection or fasting
Acute encephalopathy; previous similar episodes
Defects of energy metabolism include conditions with Recurrent coma, stroke, ataxia, cramps
deficient energy production or utilization within liver, Worsening with intercurrent febrile illness
muscle, heart and brain, e.g. mitochondrial disorders, History of aversion to sweets, high protein
disorders of glycolysis, glycogen metabolism and Developmental regression
gluconeogenesis, and hyperinsulinism. Failure to thrive,
Fa~ial dysmorphism, structural anomalies of brain, catar:ict,
hypoglycemia with high lactate, hepatomegaly, retinopathy, deafness cardiomyopathy, hepatome ga ly,
hypotonia, cardiomyopathy, myopathy, neurological myopathy
symptoms and circulatory collapse may occur. Pec~liar ~dor (musty in phenylketonuria; cabbage like in
Disorders ofcomplex molecules include lysosomal storage tyrosinem1a;. ~aple syrup like in maple syrup urine disease;
sweaty fe~t 1n 1s~valeric acidemia or glutaric acidemia type II;
diseases, peroxisomal disorders, al-antitrypsin deficiency
cat u.nne in multiple carboxylase deficiency)
and con~enital disorders of glycosylation. Symptoms are
Pe.rs1s~ent or recurrent hypoglycemia, intractable metabolic
progressive and permanent and do not have precipitating ac1dos1s, hyperammonemia, hyperkalemia
factors. Most disorders have multisystem involvement. Reye syndrome like illness
Common features include developmental delay, E. coli sepsis
organomegaly, coarse fades and arthropathy.
Others
The onset of illness in the intoxication group and in
defects of energy metabolism is often sudden, with Family history of similar illness, unexplained sib deaths, or
progressive neurological disease
nonsp~cificyhysical findings. The course may be recurrent
Parental consanguinity: Most acutely presenting metabolic
and ~p1sodic, and response to supportive therapy is rapid.
disorders are autosomal recessive.
In disorders of complex molecules, the onset is gradual
644
Inborn Errors Of Metabolism I 645 -
-
ACUTE PRESEHTATIOU
... ' -
normal. In urea cycle disorders, ammonia levels usually
exceed 1000 µg/ dL and cause respiratory alkalosis with
Nconatc1; with metabolic disorders are usually normal at compensatory metabolic acidosis. In organic acidurias,
birth .!lincc the 5malJ intermediary metabolites are ammonia levels are <500 µg/ dL and in fatty acid oxidation
eliminated by the placenta during fetal life. Disorders of
defects <250 µg/ dL.
glucc~!, protein and fat bwakdown usually present early;
Urine metabolic screen includes pH, ketones and
premature neonates with transient hyperammonemia of reducing substances. Urine is examined by ferric chloride,
newborn (THAN) and term babic.-s with glutaric acidemia
dinitrophenylhydrazine and nitroprus~ide te~ts for PKU,
type J1 or pyruvatc carboxylase deficiency may present organic aciduria/maple sy~up ur~ne disea.se and
on the fin~t d ay of life. Early onset of symptoms is homocystinuria, respectively. B1ocherrucal screerung may
as&ociatcd with bcvcrc disea se. An important clue to be normal in asymptomatic patients. .
diagnosiMis unexpected dctc.--rioration after normal initial Specialized tests such as quantitati~e ~lasma ammo
period in a full terrn baby. Neonates with organic aciduria, acids analysis by high performance hqmd chroma_to-
urea cycle cfow rd ern and some aminoacidurias may graphy (HPLC), acylcamitine profile on plasma or dned
pww nt with lethargy, poor feeding, persistent vomiting, blood spot by tandem mass spectrometry (TMS) and
scizurcH, tachypnca, floppiness and body or urine odor. urinary organic acids by gas chron:iatogr~phy a':'d m~ss
Conditions s uch a s s epsis, hypoxic ischemic spectrometry (GCMS) help in reachmg a d1agnos1s. Urme
encephalopathy and hypoglycemia should be excluded. samples should be obtained during the acute phase_ of
I
Older children ~how acute unexplained, recurrent illness and frozen at -20°C. It is advisable to provide
episodes of alte red sen sorium, vomiting, lethargy details about drugs, diet and fluids given to the patient
progressin~ to coma, stroke or stroke-like episodes, ataxia, while ordering these tests. A pretransfusion sample is
pHychiatric foaturcs, exercise intolerance, abdominal pain, preferred, if blood transfusion is planned. All samples ~
quc.1dripMc1>is or arrhythmias (Table 24.1). The symptom should be promptly transported to the lab. Examinations
free period may be prolonged, often longer than 1 year and of cerebrospinal fluid, chest X-ray, echocardiography,
patients arc normal in between the episodes. Intercurrent ultrasound abdomen, computed tomogra phy and
ilJncsscs, high protein intake, exercise, fasting and drug magnetic resonance imaging of the head and
inlnkc may precipitate symptoms. Encephalopathy occurs electroencephalogram (EEG) are required in specific cases.
with little wnrning in previously healthy individuals, Based upon the abnormalities on basic metabolic
progresses rapidly, may be recurrent and is not associated screening, acutely presenting IEMs are classified into five
with neurological deficits. Physical examination shows major categories: Aminoacidopathies, organic acidemia,
altered scnsorium, apnca or hyperpnea and hypotonia. urea cycle disorders, mitochondrial disorders and fatty
acid oxidation d efects (Table 24.2). Figure 24.1 describes
Laboratory Investigations the initial approach in such patients.
Metabolic screening includes measurement of blood levels
of glucose, electrolytes, lactate, pH, bicarbonate and Biochemical Autopsy
nmmonia. During neonatal period, ammonia levels are In a severely ill or dying child with suspected but
<200 µg/ dL; subsequently levels <80 µg/ dL are considered undiagnosed IEM, parents should be advised of the need
r- .. --· ··- ·-. --- -··- .. ---
I. Table 24.2: Differential diagnosis of metabolic disorders with acute presentation
Diagnosis Acidosis Ketosis Plasma Plasma NH3 Plasma Special test
lactate glucose
Amlnoacldopathles ± + N N N/-1- Blood spot for TMS and
plasma/urine amino acid;
mutation analysis
Organic +++ + i ii J,J, Blood spot for TMS and
acldemla urine GCMS; mutation analysis
· Mitochondria! ++ ± iii N N Lactate: pyruvate ratio, blood
disorders spot for TMS, urine GCMS,
muscle biopsy; mutation analysis
Urea cycle N N N iii N Plasma amino acid, urine GCMS,
disorders · urine orotic acid; mutation analysis
Fatty acid ± N ± i J,J,J, Blood spot for TMS for
oxidation defects, acylcarnitines and urine organic
glycogen storage acid; mutation analysis
disorders
GCMS: Gas chromatography and mass spectrometry; TMS: Tandem mass spectrometry
- 646 I
Suspected metabolic disorder
Poor feeding, persistent vomiting, seizures, ftoppiness, encephalopathy
Plasma amonia
High Normal
Table 24.3: Specimens taken in critically- sick children with- : ii. Provide adequate calories (0.2% saline in 10% dextrose
undiagnosed IEM J IV); intralipids (2- 3 g/kg/ day) may be infused if fatty
l . .
acid oxidation defect is not suspected.
Clinical photograph and infantogram
iii. Correct metabolic acidosis, dehydration and electrolyte
Blood: 5 ml in heparin, separated and stored at - 70°C; 5-10 ml
EDTA blood (leukocytes), refrigerated and not frozen; few blood
imbalance. Treat intercurrent illness, if any.
spots on filter paper (acyl carnitine analysis) iv. Enhance excretion of toxic metabolites. Immediate
measures to reduce blood ammonia are necessary as
Urine: 5-1 o ml frozen in plain sterile tubes
the risk for irreversible brain damage is related to its
Cerebrospinal fluid: 3-5 ml in 1-2 aliquots frozen and stored concentration. IV phenylacetate and sodium benzcate
at-70°C with L-arginine (Table 24.4) are used as detoxifying
Skin biopsy: -3 mm diameter skin (include dermis) from the agents, in urea cycle defects and organic acidemias.
flexor aspect of the forearm or anterior aspect of thigh. Store Dialysis is initiated if plasma ammonia levels >500-
at 37°C or refrigerate (not freeze) in culture medium or saline 600 µg/ dL, or if levels do not fall within 2 hours after
with glucose.
initiation of IV treatment. Hemodialysis is preferred
Liver, muscle, kidney, heart biopsy: At least two tissue biopsies to peritoneal dialysis and exchange transfusion.
of about 1 mma, one immediately frozen in liquid nitrogen and
Carnitine eliminates organic acids as camitine esters,
other in the glutaraldehyde
and is used in life-threatening situations associated
with its deficiency, at a dose of 25-50 mg/ kg IV over
for a biochemical autopsy for confirmation of diagnosis 2-3 minutes, followed by 25-100 mg/kg/day orally.
(Table 24.3). Specimens should be obtained before or L-carnitine should not be administered with sodium
within 1 to 2 hours of death to facilitate diagnosis. benzoate. Intractable seizures without metabolic
acidosis or hyperammonemia are treated with
Principles of Management pyridoxine 100-200 mg IV.
Specific treatment is directed towards reversing the basic v. Empiric cofactor or coenzyme therapy may be
pathophysiological process causing the disease. It administered (Table 24.5) to maximize residual enzyme
includes reduction of substrate accumulation for a activity. Long-term adherence to dietary and
deficient enzyme, reduce accumulated toxic metabolites, pharmacologic regimen is recommended. Prompt
supplement metabolites, replace deficient enzyme or recognition and avoidance of physiologic stresses
enhance residual enzyme activity (Fig. 24.2). Treatment (fever, infection, trauma, surgery, fasting) and changes
is symptomatic, supportive and often instituted in diet that may precipitate symptoms is important in
empirically. preventing metabolic d ecompensation. .
i. Eliminate dietary or parenteral intake of potentially vi. If clinical improvement is observed and a final dia~osJ.S
toxic agents (e.g. protein, fat, galactose, fructose). is not yet established, some amino acid intake is provided
- - - -- - -- -
R~ of toxic metabolite
1 Increased exaetion, transport
Oeaeased prod\Jdion
~accumulate; I Deficient
enzyme
IDeficient product I
after 2-3 days of complete protein restriction. Essential organomegaly, coarse facies, cataract, dislocated lens,
amino acids or total protein is provided orally or IV (begin chronic skin lesions, abnormal hair or urine color, and
at 0.5 g/kg/day, increased to 1-1.5 g/kg/day) until failure to thrive are useful clues. These forms are divided
diagnostic evaluation is complete. Appropriate amino into subgroups depending upon the involvement of
acid formula (free of precursor amino acids) or protein specific system (Fig. 24.3).
free infant formula ,.,..:ith breast milk is introduced with Neurologic findings are developmental delay or
clinical and laboratory monitoring. Expressed human progressive p sychomotor retardation, seizures, ataxia,
milk is preferred as it can be measured and total protein spasticity, variable hearing and visual impairment, and
intake can be quantified. extrapyramidal symptoms. Psychomotor or developmental
CHRONIC AND PROGRESSIVE PRESENTATION delay is the chief manifestation and tends to be global and
progressive; regression of milestones m ay be p resent.
This group of disorders is characterized by variable but Severe irritability, impulsiv ity, aggress iveness,
insidious onset from birth to adulthood. Unexplained hyperactivity and abnorma l behavior (automa tis m,
developmental delay with or without seizures, stereotypes, compulsive chewing of thumbs and fingers,
- 648 I Essential Pediatrics
Chronic encephalopathy
Psychomotor regression
Selz\Jres
Neurological signs
...
Yes
I
No•
l
I
+ +
Gray matter disease White matter disease ChllnUOI In •kin i
Motor difficulties
vtscaromegaly Muaclo
Seizures ± skeletal chnnges Mltochondrlol connoctlvo tl1tut1
Impaired vision Tone abnormalities dlsordors Homocyt1llnurlt1
Gaucher disease
Dementia
+
Pyridoxine dependency
i
Central only: Canavan disease,
Niemann-Pick disease
Mucopolysaccharldoses
types I, II, Ill, VII
Monkoa dl60t1!lO
F ~1coslcJo ol!I
Goloclo!llnllrlonlt1
Biotinidase deficiency Alexander disease, GM2 and GM1 GM1 gangllosldosls
Neuronal ceroid lipofuscinosis gangliosidosis (late), Sialidosis 11
GM2 gangliosidosis (early onset) adrenoleukodystrophy, Zellweger syndrome
Mitochondrial, e.g. Leigh disease, aminoacidopathies, organic aciduria
MELAS Central and peripheral: Metachromatic
leukodystrophy, Krabbe disease,
peroxisomal disorders
Fig. 24.3: Initial approach to a chronic encephalopathy. MLD metachromatlc leukodystrophy; NCL neuronal c erold llpofusclno~ln;
NPD Niemann-Pick disease; MPS mucopotysacchartdoses. Modified from: Clarke JTR. A cllnlal guide to Inherited metabolic dlseaso
I (Reference 1)
•
Laboratory Investigations
Investigations include complete hemogram, liver and Galactosem/a
renal function tests and electrolytes. Anemia and There are three disorders of galactosc metabolism
thrombocytopenia are important features of Gaucher (Fig. 24.8), but it is the deficiency of the enzyme galactose-
disease; pancytopenia may be seen in propionic and 1-phospha te uridyltransfcrase (GALT), that is referred to
methylmalonic acidemia. Peripheral smear may show as classical galactoscmia. Deficiency of GALT results in
vacuolated lymphocytes in neuronal ceroid lipofuscinosis, accumulation of galactose-1-phosphate and other
fucosidosis and sialidosis; acanthocytosis in abetalipo- metabolites (e.g. galactitol) that have toxic effects on the
proteinemia and Hallervorden Spatz disease. Adrenal liver and other organs.
insufficiency is frequent in patients with adreno- Patients are normal at birth, but by 3-4 days of breast
leukodystrophy. Metabolic acidosis with proximal tubular milk or formula feeding show life-threatening disease with
dysfunction is present in patients with Lowe _syndrome, vomiting, diarrhea and poor weight gain. Jaundice and
cystinosis, Wilson disease and ~alactosemia. Neuro- liver dysfunction are progressive and appear at the end
imaging, electrophysiological studies an~ skeletal survey of first or second week of life. The disease may present
are useful for various neurodegenerahve and storage initially with indirect hyperbilirubinemia due to hemolysis
disorders. secondary to high levels of galactose-1-phosphate in
Bone marrow aspirate is useful to rule out specific erythrocytes. Many affected infants die of E. coli sepsis in
storage disorders. Enzyme assays for v~rious s_to.r~ge the neonatal period. Untreated infants, if surviving the
disorders are now available and provide defmih~e neonatal period, have persistent liver disease, cataracts
diagnosis. Estimation of plasma lev~ls of l~ctate, amm~~·a, and mental retardation. Acute galactose toxicity may
very long chain fatty acids and ammo acids are use .f1!' rarely cause chiefly neurologic symptoms. Proximal renal
certain cases. DNA molecular testing is the most speci ic tubular disease presents with metabolic acidosis,
form of diagnostic testing and is useful for prenatal galactosuria, glucosuria and aminoaciduria (Fanconi
diagnosis. syndrome).
The diagnosis is confirmed by either enzyme or specific
Management mutational analysis. A negative urine dipstick by glucose
A multidisciplinary team of metabolic ~peci~lists, pediatr~c oxidase method with positive Benedict reaction indicates
.
neuro1ogists, . . 1 geneticist/ cardiologist,
c1rmca . orthopedic
. . h non-glucose reducing substances, e.g. galact~s~. or
d h . therapist is reqmred to maxmuze t e fructose. A negative test does not eliminate the possibility,
surgeon an P ysio . Su l of deficient especially if the patient has received N glucose for more
supportive care in these patients. PP Y. .
enzyme (enzyme rep 1acement) , e nhancing residual . . than a few hours.
enzyme activity. through co fac t o r and megavitamm .
fuerapy (enzyme enhancement/ organ transplantation~, or Management: If the diagnosis is suspected, whether or not
. o f sub s tra te accumulation (substrate reduction) urinary reducing substances are found, galactose-
red uction
are available for these disorders (Fig. 24 ·2)· containing feedings should be discontinued and replaced
- 650 Essential Pediatrics
II
jaundice, ascites
encoded by FAH Repeated neurologic blood, urine
crises; change in mental status, Confirmation by genetic testing
peripheral neuropathy Therapy: Nitisinone• (NT8C 1 mg/kg/day)
Death occurs <1 O years from liver Dietary restriction of phenylalanine and tyrosine
failure or cancer, neurologic crisis Liver transplant for liver failure, cancer,
failure to respond to NT8C
Homocystlnurla Deficient Manifestation after 3-4 years of age Urine nitroprusside test; high plasma levels of
Autosomal recessive cystathionine Developmental delay, seizures, methionine, homocysteine
13-synthase; psychiatric problems, extrapyramidal Confirmation by genetic testing
encoded by signs, marfanoid, osteoporosis Therapy: Lower plasma homocysteine levels
CBS Ectopia lentis by 8 years; myopia (< 15 µmol/L)
Thromboembolism a cause Methionine restricted diet; oral betaine
of early death and morbidity 86 (200-1000 mg/d; responsive 50%)
If folate, 812 deficiency: folate (5 mg/day),
hydroxycobalamin (1 mg IM/month)
Vitamin C for endothelial dysfunction
Alkaptonurla Deficient Urine turns brown black on GCMS can identify, quantify homogentisic acicl
Autosomal recessive homogentisate standing; staining of diapers No specific therapy; vitamin C
1,2-dioxygenase Grey discoloration of sclera, prevents ochronosis
ear and nose cartilage (ochronosis)
after 30 years
Arthritis of shoulders, hips
Renal stones
by soy based or lactose free formula pending results of Hereditary Fruc tose Intolerance
confirmatory enzyme assay or genetic studies. Galactose The condition occurs due to deficiency of the enzyme,
restricted diet is required throughout life. aldolase B. Symptoms occur following ingestion of
Galactokinase deficiency: This deficiency is rare. The only fructose or sucrose and present with intractable vomiting
significant abnormality is cataract due to accumulation and symptomatic hypoglycemia. Prolonged exposure
of galactitol. Liver, kidney and brain symptoms are not results in failure to thrive, dislike for fruits and s·weets,
seen. Galactose free diet, leads to improvement and irritability, hepatomegaly, abdominal distension, edema
prevents further damage. Galactose restricted diet is and jaundice. Investigations show hypoglycemia, lactic
required throughout life. acidosis, hyperuricemia and deranged liver function tests,
I es1
Table 24.a: Urea cycle defects and organic acldemlas
Disorder Defect Clinical features Diagnosis, treatment
Urea cycle defects Urea cycle is composed of Hyperammonemla (ammonia
Classic: Neonates
Urea cycle is the main 6 enzymes (Fig. 24.5) >80 µg/dL after neonatal porlod)
have poor feeding,
pathway ror removing normal anion gap end glucose
Defects of these enzymes vomiting, tachypnea, hypo·
highly toxic ammonia, lead to hyperammo- thermia, irritability, seizures, level
de(rved from nemia and deranged amino Plasma amino acid analysis and
lethargy and coma
cataboOsm of amino acid metabolism (Fig. 24.6) Partial deficiency: urinary erotic acid can distinguish
acids Symptoms delayed for specific defects (Fig. 24.6)
months or years; often Enzyme activity; genetic tasting
triggered by stress, high Therapy: Removal of
protein intake or illness ammonia (Table 24.4)
Arginase deficiency: Restrict protein lntako
Specific symptoms; (essential amino acids
spastic dlplegla, dystonla, 0.25 g/kg/d)
ataxia
Organic acldemlaa Deficiency of specific Insidious onset with Abnormal basic metabolic
Autosomal recessive enzyme in pathways of few/no acute crises or an screening (acidosis, ketosis, hyper·
disorders; excretion amino acid degradation, acute metabolic encephalopathy ammonemla, hypoglycemia),
of non-amino organic e.g. branched-ctlain amino that is precipitated by abnormal liver function tests and
acids In urine acids (leucine, isoleucine, fever, fasting or infection. neutropenla.
valine), tyrosine, homo- Multiple carboxylase deficiency Abnormal plasma acylcarnltlne
cysteine, methionine, and biotinidase deficiency: profile.
threonine, lysine, hydroxy· Additional hair and Enzyme activity; genetic testing
lysine and tryptophan skin abnormalities Acute phase: Adjunctive therapy with
(perioral eruption, alopecia) cofactors or vitamins (Table 24.5)
(Fig. 24.7)
N-ecetyl g-.itamatel
1ynlhaw
N-acetyl glutamate
Carb:amoy1 phosphate
1ynlllase(1)l
Ir - Ammonia
~
Omilhlne
-
transcarbamoylase (2)
Citrulllne
""'•\;'"'"' Aspartate
Arginine
f:
Arginosucclnate
noaucclnnt"
that&())
i
No specific amino acid elevation
.__ i_ -
[ Urine erotic acid• ]
---1 -
r-- --
[ Elevation of-specific ~m~~I~
joined into chains by cx-1-4 and cx-1-6 bond. Ingested [Galactitol J + - - ~~5.! r!_d~t~e_ - - - Gafaciose
I
carbohydrate is absorbed as glucose via the portal system,
phosphorylated to intermediate compounds (glucose-6- ATP
phospha te and glucose-1-phosphate) and stored as Glucose-1-phosphate +UDP Galacloklnase
glycogen. Glycogen is the main glucose reservoir in the
pyrophospho~ ADP
/l
UDPijlucose
liver and provides energy between meals or during
fasting. In muscle, it provides energy for contraction. Pyrophosphate G_,
al,-
ac-=t-os.:...e--1-=---,
ph,....o_s....,
ph,....a...,.te__,]
When peripheral glucose is utilized and its levels fall,
UDP-glucose
glycogen is depolymerized, bonds at branch points are Galactose-1 ·phosphale
UDPijalaclose
split and free glucose is released into blood by hydrolytic 4'-epimerase uridyllransferase
(
dephosphorylation (glycogenolysis )(Fig. 24.9). Defect in
UDP-galactose
the synthesis and degradation of glycogen causes glycogen
storage disease (GSD) or glycogenoses; most common
types are I, III and IV (Table 24.9).
Phosphoglucomutase
Issa -
Phosphorylase kinase
jGlycogen j G-
S-D-
Vl-
11~
l
Liver [
I
I
I + Muscle LGSD IX j
I Branching enzyme
Lysosom_e__.___
IGso 1vl Phosphorylase
Liver j G~p 21)
Glycogen synthatase
Pyrophosph~~-------Jr
0
:
'"' )
UTP I
Glucose -1-phosphate
1
Limit dextrins
Debranching
[S;so 111 j
.. 1 Phosphoglucomutase enzyme
l
~G
-1--j Glucose-6-phosphatase Glucokinase 1
ucose +------~...::.....:..:.::....::..:::.:_-1 Glucose-6-phosphate - - - ---i Glucose
j GSDl j
1-00'~-·~
Fructose-6-phosphate
Fig. 24.9: Schematic glucose and glycogen metabolism in liver and lysosomes. Common enzyme defects and corresponding
glycogenoses are depicted
myopathy and nonsyndromic aminoglycoside-induced and ketosis. Muscle biopsy shows ragged red fibers as well
sensory neural hearing loss. as subsarcolemmal accumulation of mitochondria.
A markedly elevated blood lactate and lactate-to- Staining for succinate dehydrogenase and cytochrome C
pyruvate ratio >30 suggests an OXPHOS defect. Other oxidase is useful. Brain magnetic resonance imaging (t. IRI)
biochemical features are metabolic acidosis, hypoglycemia and/ or spectroscopy are helpful in diagnosis.
Inborn Errors of Metabolism I e55
Ag. 24.10: (a) A 4-yeor-old child with gtycogen storage disease type I. Note the doll-like facles and protuberant abdomen due to
hepatomegaly. (band c) Pompe disease (type II) with marked hypotonio; and (d) Cardiomegaly
No specific therapy is available. Supportive treatment mucopolysaccharides are excreted in urine. Six different
includes supplementation with cofactors such as types of mucopolysaccharidoses with their subtypes nre
riboflavin, coenzyme Q, folinic acid, vitamin E, vitamin C, recognized. Their distinguishing featmes nrc described
camitine, high lipid, low carbohydrate diet and avoiding in Table 24.11 and are shown in Fig. 24.11.
mitochondrial toxins such as sodium valproate and statins. Urinary excretion of glycosaminoglycans (GAG) by 20
electrophoresis is a useful screening test. Specific enzyme
Lysosomcl Storage Disorders assays and DNA analyses confirm the diagnosis. Pnlliative
Lysosomes are one of the important cellular organelles care and multidisciplinary management nre important.
responsible for degradation of complex cellular molecules Enzyme replacement therapy is available for types I, II,
using various acid hydrolases. Deficiency of these IV, and VI, but the cost is prohibitive. An early bone
enzymes results in the accumulation or storage of an marrow transplantation has been found to be effective in
intermediate compound. Deposition of this stored material MPSIH.
in several body tissues leads to cellular damage and
Sph/ngo/ipidoses
disease symptoms.
Enzyme deficiencies in the degradation pathway of These are clinically heterogeneous disorders and include
glycosaminoglycans cause mucopolysacclzaridoses. In some GMl and GM2 gangliosidoses, Gaucher disease,
glycolipid storage disorders, neurological functions are Niemann-Pick diseases, Fabry disease, Furber disease, and
impaired due to abnormal deposition in the brain. The Krabbe and metachromatic leukodystrophy. The most
second category of oligosaccharidoses is the result of consistent feature is enlarged liver and spleen, with or
deficiencies of enzymes responsible for degradation of without neurological involvement (Gnucher disease I and
glycoproteins with a less complex polysaccharide III, Niemann-Pick disease A and B, and GMl
(oligosaccharides) than glycosaminoglycans. The third gangliosidosis). Metachromatic leukodystrophy and
category, sphingolipidoses is caused by deficiency of Krabbe disease are characterized by white matter
sphingolipid degrading enzymes. Accumulation of lipid involvement and demyelination without organomegaly.
inside the cells gives them a foamy appearance, chiefly Ga11clier disease : This is the commonest autosomal
seen in liver, spleen, lungs and marrow, with enlargement recessively inherited lysosomal stornge disease. It occurs
of these organs. All conditions have autosomal recessive due to the deficiency of the tissue e nzy me gluco-
inheritance except mucopolysaccharidosis II and Fabry cerebrosidase that splits glucose from glucosykeramidc,
disease (X-linked). Common disorders are discussed resulting in accumulation of the latter in cells of the
below and summarized in Table 24.10. reticuloendothelial system. Cerebrosidc-laden cells are
large and have eccentric nuclei with vacuolnted cytoplasm
Mucopotysocchortdoses and 'wrinkled tissue paper' appearance (Gaucher cells). It
Mucopolysaccharides constitute a major part o~ connective is characterized by visceral (hepatosplenomegC\ly), nnd
tissue and consist of units of disaccharides, rutrogen and bone marrow involvement leading to anemia,
esters. In mucopolysaccharidoses, acid mucopoly- thrombocytopenia, leukopenia, bony pains, fractures.
saccharides are deposited in the tissues and excreted in There may be associated neurological symptoms like
the urine. Due to lack of degradation, mucopolysaccharides developmental delay, seizures and ocular involvement.
accumulate in the lysosomes causing disorganization of No11-11e111·011opatl1ic (type l) is the commonest form and
the cell structure and function. Partially degraded characterized by absence of neurological symptoms. Signs
- 656 j Essential Pediatrics
------ ....._...._ -
MPS type Developmental Coarse
Table 24.11: Differentiating features of mucopolysaccharidosis l
Viscera Joint Dysostosis Corneal Urine g/yco-
delay facies• megaly contractures multiplex•• clouding saminog/ycans
Hurler/IH +(severe) + (severe) + + + + Dermatan
Scheie/IS +(mild) ±(mild) + ±(mild) + sulfate
Hunter/II +(mild to + + + + Keratan
severe) sulfate
Sanifilippo/lll +(severe) +(mild) ± ±(minimal) - (minimal) Heparan
sulfa_te
Morquio/IV +(mild) -(laxity) + ± Keratan and
chondroitin
sulfate
Maroteaux- + + + + + Dermatan
LamyNl sulfate
SlyNII +(severe) + + + + ± All except
keratan sulfat2
• Depressed nasal bridge, thick lips and ala nasi, enlarged tongue and peg-like teeth
•• Dysostosis multiplex refers to thickened skull, deformity of sella turcica, broad spatulate ribs, beak shaped vertebrae and proximal taperir.q of
metacarpals
and symptoms can develop at any age and include anemia, and swallowing difficulty, opisthotonus, head
fatigue, poor growth, delayed puberty, easy bleeding and retroflexion, spasticity and trismus, abnormal eye
bruising, weak bones, bone and joint pain, fractures and movements, oculomotor apraxia (trouble in moving eves
enlarged liver and spleen (Fig. 24.12a). to look side-to-side, need to tum head to see things on the
Neuronopathic forms show involvement of the central side), saccadic initiation failure (failure in starting fast eye
nervous system. Two types are distinguished by the rate movements) and optokinetic nystagmus, dementia and
of neurological progression. Type II (acute neuronopathic) ataxia, generalized tonic-clonk seizures and progressive
presents early in fetal life as hydrops or in early infancy myoclonic epilepsy.
with neurological signs and involvement of spleen and Diagnosis is made by measuring glucocerebrosidase
liver involvement. Course is rapidly progressive leading levels in leukocytes or skin fibroblasts. Serum chitotrio-
to early death by 2-4 years. Type III Gaucher disease sidase levels are elevated. Neuro-ophthalmological
(chronic neuronopathic, Fig. 24.12b) a chronic form with investigations, hearing assessment by brain evoked
indolent course and manifestations in early childhood. response audiometry, EEG and neuropsychometry tests
Signs and symptoms are same as in type 1 except that are required. DNA analysis is helpful in assessment of
neurological involvement is slowly progressive and leads phenotype and prenatal diagnosis.
to death by second or third decade. Neurological This was the first storage disorder for which treatment
symptoms include developmental delay, stridor, squint was available, chiefly as enzyme replacement therapy and
Inborn Errors of Metabolism I ss1
fig. 24. l l: Mucopolysaccharidoses: (a) Patient with type IH disease showing corneal clouding and coarse facial features; (b) MPS,
type 11 without corneal clouding but with facial coarseness; (c] MPS IHS (milder phenotype) with restriction of joint movements;
(d) Short trunk with· barrel-shaped chest and sternum protruding forward in MPS IV (morquio disease); (e) Mild facial coarseness in
A child with MPS Ill; (f) MPS VI (Marotaeux-Lamy) with abnormal skull and facial coarseness; (g) Becking of the inferior margins o f
vertebrae and proximal pointing of metacarpals in MPS type I; (h) Central becking of the lumbar vertebrae with proximally pointed
metacarpals and short ulnae in MPS IV
substrate reduction therapy. The former provides deficient with type I Gaucher disease with mild to moderate
enzyme to allow breakdown of fat in cerebroside laden manifestations for which enzyme therapy is not an option.
cells. Enzyme replacement does not have much effect on Splenectomy increases the risk of progressive skeletal and
neurons so CNS manifestations are irreversible. Therapy pulmonary disease. Stem cell transplantation is a potential
is recommended in types I and III but not in type II. option.
Substrate reduction therapy means reducing the
production of fatty material, thereby avoiding cellular Metacliromatic le11kodystropliy: Sulfated glycosphingolipids
accumulation. Miglustat is oral treatment for adult patients accumulate in white matter of the central nervous system,
- ssa I Essential Pediatrics
Peroxlsomal Disorders
Peroxisomes are involved in the oxidation (~-oxidation of
phytanic acid and of very long-chain fatty acids, VLCF~)
as well as synthesis of plasmalogens. Based .u?on t~eu
functioning, peroxisomal disorders can be divided mto
two major groups.
Disorders of peroxisomal biogenesis or importation are
Fig. 24.12: (a) Gaucher type l : Note protuberant abdomen
caused by defects in the transfer of pr?teins produced in
due to hepatosplenomeagly; and (b) Gaucher type Ill: Note the cytosol into the peroxisomes. This includes Zellweger
trismus and ophthalmoplegia syndrome (Fig. 24.13), neonatal adre~oleuk?dystrophy
and infantile Refsum disease and rhizomehc chondro-
stains them purple with a brown background, resulting in dysplasia punctata (Fig. 24.14). These disorders have
metachromatic staining. autosomal recessive inheritance and are caused by defects
Ag. 24.15: Brain MRI findings In X-llnked adrenoleukodystrophy. T2-welghted axial Images show symmerricol hyperintense s!gncl
changes Jn bilateral perleto-occlpital white matter and splenlum of corpus callosurn (Courtesy: Dr. Atln Kumar. AllMS. New Delhi)
Suggested Reading
• Clarke ]TR. General principles. In: A clinical guide to inherited • S.i udubra)' )1\1, "''" den Ber~h·• G. W.tlter JH. lnl:>om mt'ral:>olic
metabolic diseases, 3rd edn. New York: Cambridge University diseases: Di.1~n os i s .md trc.1tm.-n t. :>th t'<in. Sprinser l\IN IZin;
Press, 2006. 2011.
Chapter
25
Ophthalmic Disorders
Radhika Tandon
Children may present with varied primary eye problems. II. Family history of any of tile following
Several systemic diseases have ocular manifestations, • Rctinoblastoma
some of which are very useful in making the correct • Childhood cataract
diagnosis and instituting appropriate management. Also, • Childhood glaucoma
therapies for some diseases are known to have ocular side • Refractive errors in early childhood
effects which need to be recognized. Rarely, medications • Retinal dystrophy or degeneration
for eye diseases can have systemic side effects. Finally • Strabismus and/or amblyopia
diseases beginning in the eyes and adnexa can have • Sickle cell disease
systemic complications. • Syndromes with ocular manifestations
• Nontraumatic childhood blindness
PEDIATRIC EYE SCREENING III. Signs or symptoms reported by the family, henltf1 care
The concept of screening children for eye diseases is based provider or school teacher
on the awareness that infants and young children cannot • Defective ocular fixation or visual interactions
communicate their symptoms and visual difficulties. In • Abnormal appearance of the eye(s)
addition, several potentially blinding diseases manifest in • Squinting or tendency to close one eye in certain
this age group; their early detection and treatment can limit situations
ocular morbidity and prevent irreversible blindness. • Any obvious ocular alignment, movement abnor-
mality, head tilt or nystagmus
The goal of pediatric eye screening is to detect eye and
visual disorders in children or identify their risk factors • Large and/ or cloudy eye(s)
so that the child can be referred for detailed ophthalmic • Drooping of the eyelid(s)
evaluation, confirmation of diagnosis and appropriate • Lumps or swelling around the eye(s)
medical management. • Persistent or recurrent tearing, sticky disch.-i rge,
redness, itching or photophobia
Comprehensive Pediatric Eye Evaluation • Learning disabilities or dyslexia
Presence of any of the following risk factors is an indication
for referral for comprehensive ophthalmic evaluation. Guidelines for Examination
I. General 11raltlz co11ditio11, systemic disease or use of Children are best examined in a comfortable and friendly
mrdicafio11s associated wit/1 etje disease environment. Very young chiJdren can remain in the lap
• Extreme prematurity (gestational age :530 weeks); of their mother while older children can be distracted with
suspected retinopathy of prematurity toys and colorful objects. When the child first enters the
• Intrauterine growth retardation room, simple observation of behavior, fixation, movement
• Perinatal complications and general awareness of the surroundings are good
• Neurological disorders indicators of the child's visual status, and gross abnor-
• Juvenile rheumatoid arthritis malities can be detected.
• Thyroid disease Steady fixation and uniform steady alignment of the eyes
• Craniofacial abnormalities develop in the first 4-6 weeks. Visual acuity assessment in
• Diabetes rnellitus children less than 6 months of age is limited to seeing if the
• Syndromes with known ocular manifestations child attempts to fix and follow light. A child 6-12 months
• Chronic steroid therapy; use of hydroxychloroquine of age can follow and even reach out towards colorful
or other medications known to affect eyes objects, and this permits a very crude assessment of gross
• Suspected child abuse visual ability. A more objective assessment can be made
660
,..... .
1-
older can be tested with more conventional vision testing
lid coloboma, severe corneal opncity or lo in I cal.ll'.tct wllli
methods using a Snellen visual acuity chart with either
a white opaque lens. Sometimes tlw di ~K·a 11 1• lti IH'c•H<:nt ilt
alphabets or tumbling E or Landoldts C symbols (Fig. 25.1).
birth, but is detected later on, for cxa mpl1!, ii parli.11 c;il.iracl
Ocular movements and external examination of the eye
or mild congenital glaucoma. Somcli11wr; llu· d i111•:i t11! Iii 11
can be performed by using adequate illumination with a
defect of development but manifoslr; l.:iter, mid i ai-1 dc•vi.•·
torch and aided by toys or colorful pictures to capture the
lopmental cataract or juvenile glaucornn,
child'sattentionandinteresttocooperatewiththeexaminer.
Pupillary reactions must be tested and fund us examination
Disorders In Development of the Whole Eyeball
should be attempted with a direct ophthalmoscope
(Globe Abnormalities)
A child may be born with a smnll eye (micrnphtl1:-ilmcm or
VH oc m3
Abnormalltles of Development of the Orbit, Eyollda and
Adnexa (Lacrlmal Drainage System and Glands)
Children are sometimes born with the eyes compl ct·11ly
XUA c 0 0 WEm covered by the eyelids so that the globe is not nppa rcnt or
visible (cryptophthalmos). A blocked nnsolacrirna l duct
HTVO () 0 0 () E3Wm may manifest at birth as a dacryocys loccle, or la lc:r 111-1
dacryocystitis. Lncrimal diverticubc or fis tula a rc oilier
VUAXT 0 0 c () c abnormalities which may or may not be npparcnt a l birth.
HAVOUX . 0 0 0 0 c 0 9 Ill 9 E m &U Telangiectasins and vasculnr abnormalitieH s uc h Mi
.
Y U IC T M A 0 V D 0 0 0 0 0 0 un••1111111
capillary or cavernous hemangioma, lyrn ph hemangiuma,
arteriovenous malformations and orbHnl varices may be
present as isolated abnormalities or as part of syndromes
such as the phakomatoses.
Fig. 25.1: Snellen visual acuity testing charts. The charts are
printed on a semitransparent plastic sheet and mounted on Other abnormalities of the lids include abnormnl Hhapc
an Illuminated box. Vision Is tested at a distance of 6 metres. and position such as blepharophimosis, ptos is, promine nt
The chart on left Is In English, can be available In other languages epicanthic folds, lid coloboma, congenital ichthyos iR,
and Is used for children who are able to read. The chart In the entropion and ectropion, Early oculoplastic rccons l rucllon
middle Is the C chart and on the right the E chart, both of which needs to be undertaken if the visual axis is covered or lho
can be used for pre-school children who can understand and cornea is at risk of exposure kerntopathy due to lag-
communicate the directions ophthalmos or inadequate lid closure.
662 Essential Pediatrics
Infections
•
Preseptal cellulitis and orbital cellulitis manifest as swelling
and inflammation of the eyelids, are differentiated clini-
cally, and often occur due to spread of infection from the
lids, adnexa or paranasal sinuses or following trauma.
These are potentially dangerous infections as they involve
the anatomical 'dangerous area of the face' and if not trea-
ted promptly and adequately, can spread intracranially,
Fig. 25.2: Child with bilateral congenital corneal opacity due resulting in meningitis or cavernous sinus thrombosis.
to anterior segment dysgenesis. Differe ntial diagnoses include Ultrasonography is required to detect an orbital abscess,
all causes of congenital corneal opacity, congenital glaucoma
which has to be drained. CT scan or MRI is required if
with buphthalmos and corneal edema due to raised intraocular
involvement of adjacent paranasal sinuses or intracranial
pressure
involvement is suspected. Treatment requires systemic
ACQUIRED EYE DISEASES antibiotics and anti-inflammatory agents, supplementation
with topical antibiotics, and supportive measures, inclu-
Nutritional Disorders ding lubricating eyedrops to prevent corneal damage.
The most important condition in this category is vitamin A . ?ther infections involving the eyelids include blepha-
deficiency which can be catastrophic in young children if nhs, hordeolum externum (stye), hordeolum internum.
severe enough to produce keratomalacia. Up to the age of (infected chalazion), molluscum contagiosum and phthiri-
six months, children have adequate hepatic reserves of asis of the eyelashes. Lid hygiene, hot fomentation and local
vitamin A. However, if the mother's nutrition is poor or antibiotic oint?'ents are useful along with instructions for
the infant is not properly fed afterbirth, severe vitamin A personal hy_g1ene. P_hthiriasis will require mechanical
deficiency may be precipitated by an attac~ of acute rem~val of mts a~heru~g to the eyelashes, local applicatio~
respiratory infection such as measles, p~eumoma ?r acute ~f 20 Yo fl ~orescein sod mm to the lid margins and systenuc
gastroenteritis, which could lead to bilateral blindness ivermec~m therapy for recalcitrant cases, along with advice
due to severe keratomalacia (Fig. 25.3). Milder forms of on hygiene and treatment of other affected fam.ilY
vitamin A deficiency may manifest with xerosis of the members.
conjunctiva, Bitot spot and nyctalopia or night blindn~ss. Common infections of the ocular surface include con-
Adequate nutritional advice to the pregnant and_lactati~g junc~iviti~ ~~ich co~ld be bacterial, viral or chlamydia!.
mother and proper weaning with vitamin A nch fr~1ts ConJunctiv1hs occurring within the first month after birth
and vegetables is advised. Keratomalacia is treated with . is called_opht~almia ne.onatorum. Every effort should be
oral vitamin A 200,000 IU stat followed by a second dose made to ~dentify the eh~logic agent, especially in cases of
after 24 hours and a third dose after 2 weeks. In case the ophthalmta neonatorum, since gonococcal conjunctivitis can
.....
Ophthalmic Disorders 1663 -
cause loss of vision in the newborn. Conjunctival smears natamycin (5%) 1 hourly with supportive measures. Herpes
and swabs can be sent for microbiological evaluation. simplex viral keratitis is treated with topical acyclovir 3%
Mucopurulent conjunctivitis is treated with topical anti· eye ointment for epithelial involvement and systemic
biotic eyedrops and supportive measures such as cleansing acyclovir for herpetic keratouveitis or recurrent disease.
the eye with clean water, lubricating eyedrops and cold Other infections include endophthalmitis (traumatic,
compresses. metastatic, or iatrogenic following intraocular surgery)
More severe infections include keratitis and corneal and parasitic infestations, such as toxoplasmosis, toxo-
ulcers (Fig. 25.4). Trauma is the most common underlying cariasis, and cysticercosis of the eye, extraocular muscles
predisposing factor, but poor hygiene and lowering of or orbit.
local immunity secondary to chronic inflammation, viral
infections or use of topical steroids are other risk factors Allergic and Inflammatory Diseases
for bacterial and fungal infections of the cornea. Trauma Children may develop allergic diseases of the skin around
with vegetative matter, such as a thorn, tree branch or the eye and the ocular surface and conjuncti~a. De~a~tis
wooden broomstick (often used for making 'bows and may be an allergic reaction to local ophthalrruc medication
arrows' for playing), predisposes to fungal infections. or sometimes secondary to insect bite, application of
Corneal ulcers require an examination under anesthesia traditional eye medicines or herbal remedies and use of
for detailed evaluation and corneal scraping for micro- local creams or lotions. In addition, a variety of environ-
biological analysis. Empirical therapy for bacterial corneal mental and hereditary factors may interplay to produce a
ulcers is started with a combination of freshly prepared variety of allergic conjunctiva! manifestations such as
fortified topical antibiotics such as 5% cephazolin and 1.3% seasonal allergic conjunctivitis, hay fever conjunctivitis,
tobramycin eye drops hourly and half hourly alternately perennial or chronic allergic conjunctivitis, a topic allergic
round the clock for the first 48 hours. After 48 hours, the conjunctivitis and vernal keratoconjunctivitis. Itching,
culture report and clinical response are reviewed. If there redness, discomfort, gritty or foreign body sensation,
is no substantial clinical improvement, the antibiotic is watering, mucoid or thick ropy discharge, photophobia
changed based on microbiology results. If clinically and blepharospasm are all seen in different combinations
responding to therapy, the frequency of antibiotics can be and varying degrees of severity. Treahnent includes cold
reduced to use during waking hours only, followed two compresses, topical antihistaminic eyedrops for mild cases
days later by two hourly application, then reduced to and counseling to avoid rubbing the eyes. Topical
4 hourly or 6 hourly, and discontinued a week after the corticosteroid eyedrops give quick relief but are best
ulcer has healed . Supportive measures include topical avoided in mild cases because of the danger of self-medi-
cycloplegics, hot fomentation, analgesics, antiglaucoma cation and unsupervised chronic topical use complicated
medication if secondary glaucoma is present, and antibiotic by steroid induced glaucoma and secondary corneal
ointment at night. Fungal keratitis is treated with topical infection and ulceration. More severe allergies may have
secondary consequences in the form of dry eye, kera to-
pathy and corneal ulceration. These are best referred to
ophthalmologists for expert management and careful
follow-up.
Other inflammatory diseases include phlyctenular
conjunctivitis or keratoconjunctivitis (believed to be an
'allergic' immunological reaction to tubercular antigen);
interstitial keratitis seconda ry to infections like rubella,
syphilis, leprosy and tuberculosis; and u veitis, either
idiopathic or associated with juvenile chronic arthritis,
psoriasis, tuberculosis, sarcoidosis and toxoplasmosis.
Acute anterior uveitis (iritis, cyclitis and iridocyclitis)
usually presents with a red inflamed eye with photophobia
and diminution of vision. Chronic uveitis may be less
symptomatic with decreased vision due to complicated
cataract. Intermediate and posterior uveitis (pars planitis,
vitritis, retinitis, choroiditis and retinochoroiditis) are
usually painless with symptoms of decreased vision (due
to hazy media and retinal or optic n erve swelling and
inflammation) and floaters (due to inflamma tory cells in
the vitreous). Treatm.e nt is with topical cycloplegic agents
and steroids, supplemented with systemic steroids and
specific therapy for any underlying disease, such as
--
- 664 I Essential Pediatrics
tuberculosis. Patients with uveitis need detailed exami- Sturge-Weber syndro~le and nc~us of Ota ~u1y be
nation with a slit lamp biomicroscope to identify U1e associated with cafe au la1t spots, plex1form ncurof1broinlls
inflammatory response, ophthalmoscopy to v iew the of the lids and orbit 1md Lisch nodules on the iris llnd
fundus and speciaHst ophthalmic care and follow-up to glaucoma.
control the inflammation and minimize the morbiditv Muscular dystrophies or degenerations such ns chronic
related to the disease and its treatment. " progressive extemal ophthalmoplegia result in ptosis and
lntraocular (retinoblastoma or juvenile xanthogranu- restriction of eye movements. Duchenne muscular
loma) or systemic malignant disorders may sometimes dystrophy may be associated with cataracts.
mimic uveitis syndrome due to malignant cells in the eye
and vascular uveal tracts. Tumors and Neoplastic Diseases
Optic neuritis is another important inflammatory Benign tumors include dermoids of orbit, lids or on comeii,
disease which could be idiopathic, secondary to infections hamartomas, osteoma, vascular malformations or heman-
or associated with demyelinating disorders. Classical giomas of various types and neurofibromas. Malignant
features include a rapid drop in vision, usually in one eye, intraocular tumors are confine d to retinobla stoma
which is accompanied by a relative afferent pupillary (Fig. 25.5), juvenile xanthogranuloma, medulloepithe-
defect and normal fund us (retrobulbar neuritis) or inflam- lioma and metastatic lesions from neuroblastomas, Ewing
matory swelling of the optic disc (papillitis) and retinal sarcoma, leukemias and ly mphomas. Orbital tumors
edema and/or exudates (neuroretinitis). Patients need to include rhabdomyosarcoma, Langerhans cell histiocytosis,
be treated in consultation with a neuro-ophthalmologist extraocular spread of retinoblastoma, metastatic spread of
after investigations to identify the cause. Ewingsarcoma,neuroblastoma, leukemia and lymphoma.
Glaucoma
Primary congenital and developmentnl juvenile ghn.1comn
are now recognized to be inherited discl'lscs. Prnnnry
congenitnlglnucoma is nssocintcd with CY1'7 mgene •. (2p2 ~)
with a predominantly autosomnl recessive mode of mhcn·
tance, and mutations in the myocillin (MYOC) gene.
Photophobia, blepharospasm, wntering and an enlarged
eyeball are cbssic symptoms. Susp.icion of glaucomn or
buphthalmos wnrrnnts urgent rclcrrnl .to. an op~1lhal
mologist. An examination under anl'slhcs1a 1s required to
measure thecorne'11 diameter and intraocul<1r pressure, <1nd
to visu<1lize the optic disc. Once glaucoma is confirmed,
medical thernpy is started to lower the pressure <1nd patient
prep<1red for surgery. If the comen is clear enough to allow
visualization of the angle structures, a goniotomy is nttemp-
ted. If the glaucoma is more severe or the cornea very ede1~1a
tous, a drainage procedure is undertaken to open aItemahve Fl 25 7a· The sequelae of ocular trauma. Following Injury with
aqueous drainage channels such as trabeculectomy and a ~ooden. stick. the child had corneal perforation. which was
trabeculotomy. If the cornea fails to clear after adequ~te repaired. Traumatic cataract was surgically removed. Note the
Irreversible anatomical damage with corneal scar. distorted Iris
control of the intraocular pressure, corneal transplantation
and pupil and lens capsular opaclllcatlon
is required to restore vision and prevent irreversible sensory
deprivation amblyopia.
Children can also develop secondary glaucoma due to
chronic use of topical corticosteroid eyedrops, following
Fig. 25. 7c: Following trauma with a compass. this young teenager had to be operated for trauma-Induced cataract and retinal
detachment and subsequently developed a conjunctiva! inclusion cyst
hereditary conditions like retinitis pigmentosa and factors by a premature, underdeveloped retinal vascular
different forms of macular degeneration such as Stargardt system. The chief risk factors are prematurity, especially
disease. These diseases lead to gradual, painless, bilateral birth before 32 weeks of gestation, birth weight less than
diminution of vision in the first or second decade of life 1500 g and presence of other contributory risk factors such
which may be accompanied by defective dark adaptation as supplemental oxygen therapy, hypoxemia, hypercarbia
or abnormal color vision. No specific treatment modalities and concurrent illnesses like septicemia. The clinical
are available, but refractive correction, low vision aids, features are graded in stages of severity depending on
visual rehabilitation and genetic counseling are ancillary the retinal signs and the zone of retina involved. Children
measures. at risk should be screened periodically to look for evidence
Vascular abnormalities of the retina such as heman- of developing what is considered as 'threshold' disease,
giomas, arteriovenous malformations and exudative i.e. requiring ablative laser treatment of the avascular zone
vitreoretinopathies like Coats disease may be seen. Retinal of the retina to check further progression and prevent
vasculitis may be seen in Eales disease and other inflam- blinding stages of the disease which would then require
matory disorders. Diabetic retinopathy and hypertensive surgical intervention to treat the ensuing retinal
retinopathy can occur if these systemic disorders are detachment and other complications.
present in sufficient grade of severity and for an adequate
duration of time. An important disease seen only in Blindness and Low Vision in Children
children is ROP. The World Health Organization (WHO) has categorized
blindness in different levels based on the extent of vision
Retinopathy of Prematurity loss. Vision 2020: The Right to Sight is a global initiative
This condition unique to children is seen in preterm babies for the elimination of avoidable blindness, a program
due to early exposure to oxygen and other environmental jointly run by the WHO and The International Agency for
*Visual field <40° up to 20° across, around centre of fixation or hemlanopia involving macula
tVisual field <20° up to 10° across, around centre of fixation
*Visual field <10° across, around centre of fixation
HMCF: Hand movement close to face
668 Essential Pediatrics
Fig. 25.8: Low vision and rehabilitation services: (a) Retinoscopyfor refraction; (b) Checking acceptance; (c) Child wearing prescribed
glasses; (d) Teenager using telescope; (e and f) Helping for near vision
26
Skin Disorders
Neena Khanna • Neetu Bhari
BASIC PRINCIPLES
Morphology of Lesions
Mocules
Macule is a circumscribed area of change in skin color
without any change in consistency (Fig. 26.1). A macule
may be hyperpigmented (e.g. cafe au lait macule),
hypopigmented (e.g. leprosy), depigmented (e.g. vitiligo),
or erythematous (e.g. drug rash).
-
.
. . ~~..: ·- -. .
-~
'
,,,-
. .
....;'
• I
j• ,• _, ... .· ....
multiple closely packed firm elevations, e.g. verrucous ' ... ........... ""'
warts). A papule which is >0.5 cm in size and with the major
part in the skin is called a nodule (Fig. 26.2b).
Fig. 26.2: (a) Papule: Solid lesion, s:0.5 cm; (b) Nodule: Solid
lesion, >0.5 cm
Plaque
Plaque is an area of altered skin consistency, the surface
area of which is greater than its depth (Fig. 26.3). A plaque
can be elevated, depressed or flat.
Wheal
Fig. 26.1: Macule: Circumscribed area of change In skin color Wheal, the characteristic lesion in urtica ria, is an
without any change In consistency evanescent, pale or erythematous raised lesion which
669
I s10
Fig. 26.3: Plaque: Area of altered skin consistency with a surface Fig. 26.5: Blister: Circumscribed, elevated, superficial fluid-filled
area greater than its depth lesion
-11
to dermal edema, and when the edema extends into
subcutis, it is called angioedema. When the wheals are
linear, the phenomenon is called derrnographisrn.
) '
I
Blisters
Blister is a circumscribed elevated, superficial fluid filled cavity
~
(Fig. 26.5). If ~0.5 cm, it is a vesicle and if >0.5 cm, a bulla.
Scales ·
Scales are flakes of stratum corneum (Fig. 26.6) and are
diagnostic in certain dermatoses, e .g. silver easily
detachable flakes in psoriasis, branny scars in pityriasis
versicolor and fish-like scales in ichthyosis.
Crusts
Crusts are formed when serum, blood or pus dries on the
skin surface (Fig. 26.7). Fig. 26.6: Scale: Appears as flakes of stratum comeum
i\ll\1ph~· I~ lh1• l'l'lhH llUt1 tlf "tl1111' lll' 1111 li1y11rri 11f i1ld11, 111
1
Pattorna Formod
Amingcmc::n t 11nd configuration of skin lesions can help
In dl11gnolllH(Tnhlc 26,1).
Seborrhelc dermatitis
Fig. 26.13 : lchthyosls vulgaris: Lorge scales on extremities
that are attached at the center and turned up at the edge
lmpollgo contaglosa --=:::X:::'.L..
Acne, atoplc dermatitis,
Salmon palch port wine stain
Segmental vltlligo
Lichen
plan us
Scabies
lchthyosis
Defect Reducu d or all sent Deflcloncy ol storold Doloct/doflolonoy ol Mutation of Knratln 1 awJ f o
filaggrin that helps sullotoso onzymo lrnnoglutornlnnoo AOCA12, dr:tect
fonn kemlin lilumont ALOX12B
Age of onset 3-12 months Birth Birth Olrlh Olrth
Sex Equal in both sexes Only males Equul In both ooxoo Equal In both Equal in both sm:.r;s
00)(00
Incidence Common Amo Vory roro Aaro Raro
Clinical Fine while scales on Largo dnrk brown Collodlon boby ot birth, Collodlon baby Gr:nGrallz."..ld
features most parts of body adherent scales onohoothod In ohlny nt birth; followed erythc:m:J with
Large mosaic-like (Fig. 26.14) lacquor·llko rnornbruno by fine branny bliW;rin~J at
scales. attached which on ohodcJlng acalos and birth. Follcmed b'/
(at center and rovoalo cJlfhmo largo markod brown, 'llBrty,
upturned al edges th ick brown plnto·llko orythema broad linear
on extensors of scnlos (Fig. 26.15) (Fig. 26. 16) plaques (Fi~ . 26.1 7).
lower extremities which persist for llfo; Scales rna1 fall off
(Fig. 26.13) erythoma minimal leaving skip ;:ireas
Sites of Extensors of limbs; Generalized Gonorallzod lnvolvo- Generalized Genc: ralizP.d
predilection major flexures always Involvement; mont; accentuation erythema and involverm;nt;
spared: face usually encroachment of on lower limbs scaling accentuation in
spared flexures; palms and flexures flexures
and soles spared
Associated Hyperlinear palms and Corneal opacities; Ectroplon and Palmoplantar Palmoplantar
features soles: keratosis pilarls; cryptorchidlsm eclabium; crumpled keratoderma keratoderma in
atopic diathesis ears; palmoplantar less frequent >60°/o
keratoderma
CHnicol Features
Inherited PPKD is characterized by thickening of palms
and soles which usually manifest at birth or in the first
few months of life. The thickening may vary from mild
to moderate (Fig. 26.19) or may be severe, in which case it
mav be mutilating (Fig. 26.20). The keratoderma may be
restncted to palms and soles or spill on to dorsae of hands
and feet (keratodenna transgradiens; Fig. 26.21).
Treatment
Therapy for PPKD includes use of emollients, keratolytics
Fig. 26.17: Kerotinopothic ich1tryosis: Brownish, warty, brood
linear plaques (salicylic acid 6%, urea 30-40%), topical retinoids and
vitamin D (calcipotriol), all used after soaking in water.
In mutilating variants, treatment with oral acitretin may
be warranted.
I
Fig. 26.18: Collodion baby: Baby is ensheothed in a shiny
lacquer-like membrane
Flg. 26.19: Palmoplantar kerotoderma: Autosomal dominc•i
variant, with thickening of palms
Collodion babies are at risk of thermoinstability,
hypernatremic dehydration, skin infections, pneumonia
and sepsis.
Treatment
Since collodion babies are frequently at risk of several
complications, they are best managed in a controlled,
humidified environment, carefully monitoring for fluid
and electrolyte imbalance. Skin care (frequent application
of emollients) and eye care are paramount. Oral acitretin
is often needed.
wtth keiotodermo ~pllllno onlQ ct01~(1fl 01 iaPt 1h1l'i11lri111tl1'Vl'l11111111•11l11I ') 111111111 1• 111111111111 d11il •111d1111111
11111111·1·1111il• Pl l11d1J1111 . ., 1111 dlt1111d111t1 11111 I l1illfllll11,f 11111;11,f
Eptdermolysls Bullosa 11111tlll1t11 111111'1 il11111 ·11 !Al I, Al< 1111d Xr.1 1 ) 11/ l1y 111111• lll ll'l:I
l11v11lv11d (111111'1 ll'1 1llt, 1111111:1, 11w1111l 111l1111d111,
Epictermolysis bullns,, "1'l' ,, hl'l1'rn>\1'n1,1H1tl >\l'IHll' 11f
ctisorcit.'t':' ddiiwd by ,, h'1Hh-1w~· II\ d1'v1•h1p hll~l1•1·ri 11v1111
on trivial trauma. Sl'\'t''"'I \'•ll'lrml!'l nt' Ill\ nrti rt'\'0~11l~.11il Al 1/ 1/1 // 1 11/11 / I i/1 Jf /r-1111 111/ / /YJ if 1/ 1/11~/1 I
based on inlwl'itnnct'. ~'''"' d1'ft•l'l:1 '"'d l'llnk.11 f11(1l111•uti 'l'lw 1•oi1dlll1111 lt:i l11l11•rlt1 1rl 1111111 XI.I' 111111111111, I ldld
(Table 26,~), tm Si mph•'\ 1rnd lhH"lflill\I d)'l!ll'l\pl\I\' 1\1\ l\r\V\I pr11rw11ln wlllt l11l11lt•r11111 '1• l1dll'11t 1111rl 1•11111111f1 •ri 11l ld1~l11• 1 '11 11
<1n AD inlwritanct.', whlh• j111wtl111rnl 1\11 nnd r1ic1w1lv11 dllP Ill f'Pdll1 °Prl l1W1'1lll11g (lty1111flid111tilc:i) ,,,., 1lllt;11 111
dystrophic EB hnvc "''AR lnlwrllnnc1•. pr11r>~·1h ·1111( 11111y11 l1•w t1w1•11 t 11l11111 "1r 'I I 11 • f111 l••ti I« rl Id 11r• 11·11_•
wllh prn111l111•nl f1111•l1t•11rl, tltll'I·. l1111i 11 11d ,, fl.rt 1111c;1•,
Clinical Features t\ddlll1llhtl l1•1llllf°11r1 ft11l1td1 111111 1 Wlltd· l1•d, tf n l~ I l1fll/1 1d
1
The hallmark of llw diSt'MW I~ lcnd1'ncy 111 d11v1•lop jltll'llll IJll111 '11.. lll, '1'l11• lt1tll'l1tllP 11p11tr11•1fIJ1,l1I 111lt111'tf 1 111 j flfl!
blisters even on trivinl injury, prl'dnmlnnnlly nt rilltir; of nnd nl11w )',rnwl1111,. '1'1111lt•t•ll111111y lw ,,f 1i;•·11t tl 1 11~. '/l1 ,'/_f1) (II
trauma. Howl'\'er, there 1H1' dlffcrrnct'rl 111 ty1w oi 111'111wp,·Hhrtp1•1 I.
blistering, thl'ir ctistribullon and Sf'Vt'rily, 1:vol11llon n11d
sequelac as well ns the degree of nrnco!'lnl n11d 111111 '/'1·1•1111111•11/1 'l'IH•t'I' lrl IHI tip1•t ll k 11'1•,Jlllll'lll, J1t1f 1Jll•1flly uf
involvement in the different vnrlnntrl (Tnhl1• 26.:11 llf\l 1'1lll hi' li11p1·11v1•d hy 11111l1tl1•11111l< ,. 11( 111111 11111lii•·111
Figs 26.22 to 26.25). h1 m1wr!1111n 1 n11d ttlf11ll11)flll) (1•Vl 'I' fly l1·11ld r; p1 my, ll1r,.
,.
Toblo 26.3: Cllnloal fonluro!.I Of onl<Jmrnolyf:ll§ lmlloMl (120)
EB simplex Juncl/onnl IW Do111!111111t 1lytJtrop/1/o IJIJ f?OOflf.JtJfVI) lfyr,/tU/Jfi/f} /:U
Age of onset Early chlldl1ood At blrt11 /\I hlr1J1 1l11ltinoy /\I IJlrllt
Skin lesions Nonhemorrhaglc Largo fluccld h11llno l'IOrnonl1oulo hllt11om I l(Jnl(1rtli11yla IAl e, l11fN
bulloe which heal which honl olowly wlilol 1liunl with tlf>mu wlll<,ff llu11I •111111 t;r)tJ trlriQ
without scarring (Fig. 26.23) tio1mlno nnd 1nllln Wlu. :!0.W)
(Fig. 26.22) Wll.J. 2 0 . ~'1)
Sites Honds and feot Trunk ancJ oltoo of ~lltori of tro11rn11 Go1wmllt11d
trnuma (knoofl, Oil)OWB,
flngore). Porlorlflclol
granulation llfleuo
Mucosa! lesions None lnvolvod Mlnlmnl tlovoro
Nall Involvement Absent Proeent Pro110111 Pronunt
Complications Heal without Ono variant 6onrrlnQ nnd rnlllo Ot1V11ro r.r:11r1lr1~1; rl'f'ml0r,rnor11
scarring lothal formnllon OI cm1tr11Uuroi., lw·,11,11 ul
ululttt imcJ o.ri11pt11ilJ'JIJI
olrlr.t111'11ti
Level of split lntraepldermnl Lamina luclda Bublnmlnn cJon§a Otibluml1111 cJ1irisu
Gene defect Keratin 5 and 14 Lamlnln, collaoon XVII Collauon VII CnflO{IOrt VII
- S76 Essential Pediatrics
Neurocutaneous Syndromes
Neurofibromatoses
Neurofibromatoses encompass eight inherited disorder=-.
of which neurofibromatosis type 1 (NF l) is most commcm.
Fig. 26.24: Dominant dystrophic epldermolysis bullosa : NFl is an autosomal dominGnt disordL'r with 100·;,,
Localized Involvement of trauma prone site, bullae heal with penetrance. The defect is mutation /dell't io n of NFI
mllia formation gene.
Cli11ical feahtres: At least two of the following criteria
should be met to reach a diagnosis of r'-.Tfl:
1. S~x or m_o rc cafe au la.it macules (Fig. 26.27) which are
Skin Disortiers I ---. ::>I l
-
>::>mm m prepubertal age group or >15 mm in post-
pubertal age group.
2. Two or more neurofibromas (Fig, 26.27) of any type, or
one or more plex.iform neurofibromas.
3. Freckling in axillae or groin.
-1. Optic glioma.
5. Two or more Lisch nodules on slit lamp examination_
6. Dysplasia of the sphenoid; d ysplasia or thinning oflong
bone cortex.
7. First degree relati ve w ith NFl.
Neurofibromas which are symptomatic or have turned
malignant need to be excised.
-,
. ..,, . ..
_.. ..,~-·
'J • . , ,•
., ... ·
f . :. ... .
:" •.'- . ,."' ·. · Rg. 26.28: r_c e r'21...:; :;;:-:e-;:-s:;. .~· ..:..>,;11..';"o-:i- ··~ ·. ~ .ro.,::- :;-'--:i1
oscr~te cr;re-c-a..s :-o::ua 12$0~ ,,. - r~...J'..".f ~-..')...~" ~,·:::
bilct.ercl c nee<.S cr.c ::;..,.~ of -:·~ :::::-· :......-.;-. ~-:· -"\:1-.'..J':O \\=I
defined. o .d. n-1 cca<;;r.e-..~ --O.:-...Jo:? ;:. ~· ~ -...N..
Major features Minor features There can b~ '1..'-.~i.1tl::'\:i ,ient-.ll. '-"-'"\tbr, 1k·u r ..~: ..--d..-.11 ..;1~..:
Facial angiofibromas Confetti skin lesions deYelopmental ,mom.:tli~ .\ttn..1~'n;t'.'nt ~n..· u ..i ..~ ~';;-.- ~k
(Fig. 26.28a)/forehead plaque Gingival fibromas counseling of th~ p..m m ts .:md $ymr t\).:n ..1tk ..·..~n.'. •
Periungual fibromas Multiple dental pits
Xeroderma Pigmentosum
Ash leaf macules (Fig. 26.28b) Rectal polyps
Shagreen patch Bone cysts This is .m A R conditil)n, dut:> to dc.'t\., ·ti,·c.' nu ·k...,ti,k
Multiple retinal hamartomas Multiple renal cysts excision rep<tir of rhl)tod.1 m,1~t'i D".'\.\, .11~.i ~h.\r.h'!'\'n.:-~'i
Cerebral tumors Retinal achromic patch by extreme photo$t'n:>iti,· i t~· \m.mi t1..':'fo\~ -~ ~ .1~~1k ~m~
Renal angiomyolipoma bum) with OOS('t in infatKY. 0Yc.'r t't.c.''\.t ~""'\.- \ t'..U":' tb' ..-hil,1
Cardiac rhabdomyoma develops hyperpigm('ntt'd t frc.'' ~h.--m.~- .u~,i tn r,,~
Definite TSC: Presence of either 2 major OR 1 major+ 2 minor criteria
pigmented le:.-io ns pn.·><fomin:mtly o n the.' rlh,t\'<.''\.:'< ' c'<.i
Probable TSC: Presence of 1 major+ 1 minor criteria skin on a background l"'f :\.c.'l'\\..:.i~ (Fl_,~- :t'.:>l,). '-" c.' r t: m~'.
Possible TSC: Presence of 1 major OR 2 minor criteria most children deYelop actinic k\.'r.l.t~'\.'$ (,"I rt\.'\\Ul~-:_n.m t
- 61a 1
. l' ) basal cell cnrcinomn, squamous cell carcinoma
cond 1 ion , • ' . I ·
., Most children nlso have p 1otophob1a/
an d Jnc la n()m " 9 · ·. ..
· tivitis kcrntil1s, corneal opnc1t1cs ancl d evelop
1
con1.unc ci'cs 0 f eyelids imd conjunctiva. Neurological
mn 11gnnn . . . ,
involvement is i;ccn in a third of the patients.
1·rentme1tt Higorous sun protection O!fcstyle modific~
tions and sunscreens) rind use of topical and systei:i1c
retinoids delays and reduces de~clopmcnt of neoplas.1as.
Equally importnnt is oncosurvc11ln.nce an~ .appr~priate
treatment of prernaligmmt and malignant skin lesions.
NEVI
Nevus is a developmental disorder characterized by circum-
scribed hyperplnsia of epidermal or dermal structures.
Fig. 26.29: lncontinentia pigmenti, vesicular phase: Multiple crusted Melanocytlc Nevi (MN)
vesicular lesions over the right lower limb of a female child
MN are composed of nests ~f mela no~ytic nevus cells
and may be congenital or acquired. Acq~1red Mt;I may be
j1111ctional (with nevus cells at dcrmocp1~ermal J~ncti~n},
compound (with nevus cells a t d ~rmoep1dcrmal iunctJ~n
and in dermis) and dermal (with nevus cells only m
dermis). Of these, first two are seen in children while
the dermal variant is seen only in adults.
The clinical presentation depends on the type of MN
(Table 26.5, Fig. 26.31).
Treatment
Dermal Melanocytosis
Mongol/an Spot
Mongolian spot is a dermal melanocytosis, d ue to
entrapment of melanocytes in dermis during their
migration from the neural crest into the epidermis. The e
Fig. 26.30: Xeroderma pigmentosa: Multiple. brown to black spots present at birth (or soon thereafter) as gray blt;e
freckle-like lesions over the face and lips, associated with macules, in the lumbosacral region a nd disap pcJr
conjunctiva! congestion spontaneously by early childhood.
Nevus of Ota
Presents at birth or infancy (sometimes in adolescence)
and consists of mottled slate-gray and brown hyper·
pigmented maculcs in the distribution of the mnxillary
division of trigeminal nerve (fig. 26.32). Lesion persists
for life and is frequently associated with pigmentation of
sdera (slate-gray) and conjunctiva (brown). Pigmentation
of nevus of Ota frequently impacts child's psychosocial
development and can be reduced by treating with
Nd:YAG laser.
Epidermal Nevi Fig. 26.33: Verrucous epidermal nevus: Multip le, brovm popular
lesions, arranged linearly
These nevi usually present at birth, as multiple brown
papules arranged linearly (Fig. 26.33). Several variants Vascular ' Birthmarks'
are described, including vcrrucous epidermal nevus, Vascular 'birthmarks' are classified based on the
inflammatory linear verrucous epidermnl nevus, nnevus pathogenesis, evolution, clinical manifestations and on
comedonicus and nevus sebaceous. the presence of associations into vascular tumors and
Topical retinoic acid and dermabrasion are helpful. vascular malformations (Table 26.6).
Morphology Soft, bright nodule Telangiectatic Light pink-deep red Cluster of thin-walled
with pale stippling macules macules (Fig. 26.35); vesicles
(Fig. 26.34) bosselated with age
I Site
Complications
Face forehead, eyelids
and neck
Interfere with
function; bleeding
or ulceration
Nape of neck
None
Face
Sturge-Weber syndrome
associated with
Trunk
hamartomas;
seizures, eye deficits
Course Grows for a few months; lnvolutes by age of Persists throughout life Persists
later regresses one year
Fig . 26.34: Infantile hemangioma: Soft bright red nodule with Fig. 26.35: Port-wine stain: Light pink to deep red rnocule otten
pale stippling developing bosselation as child grows
I tHJ I
Atopic Dermatitis
Atopic dermatitis is an acute, subacute or chronic
relapsing, endogenous eczema, characterized bv drv
skin and recurrent, pruritic, symmetric dem1atitic le";;io~
The condition is due to a complex interaction betw~n
genetic susceptibility and immunological changes with
heightened IgE response.
Cllnico/ Features
Lesions develop in infancy, anytime after 3 months of
age. In children, two distinct patterns are recognized.
Fig. 26.38: Cl111dt1ood patte1n of atcplc t1( 11nlltllls. l""1v l"loquur.
Infantile pattenr: Manifests as itchy, erythematous In the fle:...'Ures
papulovesides, on the face (Fig. 26.37), but may become
generalized. The lesions clear by 18 months of age in dust mite (using b,\rrkrs \)t\ pillow~ 1\1\d m 11ll1'l':4Sl'~,
40% and evolve into childhood pattern in the rest.
regular vacuuming of mom~) nrny lwlp. Tlwn• it' "''
Childlrood pattem: Childhood pattern is characterized contraindicntions to \":t(dn \lion l..'~l'l'pl in d\ild l'l'll :;pl·d-
by dry, lichenified and crusted plaques, seen mainly on ficall) allergic to egg~. in whnm inflt1l't1:."1 11nd ~· l'll11w
fe\·er ,·,1ccines n1"C ~woidcd. Dkl,'1')' 1\•:;lrkli11ns ,11\' u~u.11lr
antecubital (Fig. 26.38) and popliteal fossa, the neck and
not warrantro and bl\\\St l\..'l'llit1g i~ l'lll'll\11\\t;l'd .1s II 11111)·
face. Most (70%) clear by 10 years of age.
decrease the chance of the infont dc\'dllping the dl ~l'.lSl',
The diagnosis is based on Hanifin and Rajka criteria
(Table 26.8). Secondary bacterial and fungal infections Skin Ct1rc: Mild sonps nnd ck•1m~ing hithm!'< 111'1..' tu b1•
are frequent. Viral infections like herpes simplex and used for bathing followed immediately h~· npplk11lh111 l'r
molluscum contagiosum may become widespread. moisturizers to skin. lfowl..'\"l'l', thl..' 1.:osl· effl..'dln-11e~s nf
moisturizers which dnim to rl'pknlsh nah11'1\l
Treatment moisturizing factors is dcbnt,\bll..'.
General measures: Care takers and the child should be Acute lesions are trenh~d with wet d1·l· :;~i ng ,11\d
counseled about the chronicity of the disease and that topical steroids. Antibiotics nnd nntifung.ll!' (h11'k1\l /
the child should avoid contact with irritants (woolens systemic) are used when indk.lh.~d. Om\ mllhi:;l.11nlnks
and chemicals). Measures to reduce exposure to house are often prescribed.
- 682 I Essentlal Pediatrics
Treatment
Treatment depends on extent and course of disease
(Table 26.10).
Mlllarla
Etiology
Miliaria is due to obstruction and rupture of eccrine sweat
ducts resulting in spillage of sweat into adjacent
epidermis/ dermis. Depending on the level of rupture,
miliaria is classified into:
• Miliaria crystallina
• Miliaria rubra Fig. 26.43: Mlllarla crystalllna: Tiny, non-Inflamed superflclol
• Miliaria profundus vesicles
I sas
PAPULOSQUAMOUS DISORDERS
Psoriasls
Etlolog/
Psoriasis is a disease of T cells, with interplay of genetic
factors (PSORS1-8 genes, and several others) and
environmental influences (physical trauma, infections and
drugs).
Based on morphology of lesions, psoriasis is classified
as chronic plaque psoriasis, guttate psoriasis and pustular
psoriasis. Based on age of onset, chronic plaque psoriasis
is classified into type 1 (onset in childhood or adolescence,
positive family history, association with HLA-CW6, severe
Fig. 26.4~: Trach~onychia: Multiple, longitudinal, linear striations disease, prominent Koebner phenomenon and prolonged
over the f1ngernrnls associated with roughness of nail surface
course, requiring aggressive therapy) and type fl psoriasis
Pachyonychla Congenita (onset in adults).
It is a rare autosomal dominant disorder, characterized Clinical Features
by gross thickening (tenting) of nail plates (Fig. 26.45a),
Chronic plaque psoriasis (CPP): CPP is characterized by
oral lesions in form of leukoplakia (Fig. 26.45b) and
well-demarcated, indurated, erythematous, plaques
keratoderma of palms and soles.
surmounted by silvery scales (Fig. 26.46), which are
accentuated on grating the lesion with a glass slide
(Grattage test). Removal of the scales by further scraping
reveals a glistening white membrane and on removing
the membrane, punctate bleeding points become \"isible
(Auspitz sign). Lesions become poly cyclic due to
confluence and annular because of central clearing.
Symmetrical involvement of knees, elbows and extensors,
lower back, scalp and sites of trauma (Koebner or
isomorphic phenomenon) is seen. Face and photo-exposed
areas are generally spared.
Guttate psoriasis: It typically occurs in children and
adolescents and is characterized b y crops of s m all,
erythematous scaly papules, predominantly on trunk.
Guttate psoriasis is often triggered b y streptococcal
tonsillitis.
Fig. 26.45: (a) Pachyonychia congenita: Massive thickening of the Fig . 26.46: Chronic plaque psoriasis: Well -d emarcated ,
ml plates resulting in tenting of nails; (b} Leukoplakla of the tongue lndurated. erythematous plaques surmounted by slivery scales
- sea 1 Essential Pediatrics
I
average course of about 1 year.
Mid-potent topical corticosteroid or topical tacrolimus
can be used in children to relieve the pruritus.
Phototherapy has been tried in refractory cases.
Lichen Strlatus
Lichen striatus is characterized by presence of hyp o-
pigmented/ erythematous papular lesions configured
linearly usually on the limbs. Active lesions subside
spontaneously, leaving behind atrophic, post-inflammatory
hypopigmentation (Fig. 26.50). Counseling about the self-
Fig. 26.47: Annular pustular psoriasis: Superficial pustules which lirniting nature and that it is not vitiligo is often all that is
coalesce to form annular lesions required.
Ag. 26.48: Lichen planus: Polygonal. flot·topped, violaceous Fig. 26.50: Lichen strlatus: Hypopigmented atrophic mocules
pcpules configured linearly over left forearm
Pityrlasis Rosea
Table 26.12: Treatment of lichen planus in children
Etiology
Type of disease Therapy"
The condition may be triggered by reactivation of human
Localized Topical steroids
herpes viruses (HHV-7, HHV-6).
Extensive Narrow band UVB
Oral steroids Cl/nlcal Features
Acitretin PR begins with a 'herald patch' in 80% cases. Lesion is
characteristically oval, wrinkled with a collarette of scales
Scalp lichen planus Oral steroids
at the periphery. This is followed by multiple, smaller,
Mucosal lichen planus Dapsone and topical steroids oval to round scaly secondary eruptions. Their arrange-
in orabase ment is characteristic as lesions run downwards and
Oral steroids outwards from the spine (Christmas tree appearance)
Acitretin along lines of cleavage. The condition is self-limiting, with
the lesions resolving spontaneously within 2-10 weeks.
·0ra1 antihistamines to be added, if lesions itchy No treatment is usually required. Oral antihistamines,
calamine lotion and topical steroids may be used to
decrease itching. Recalcitrant lesions may be treated with
ultraviolet light.
Erythroderma
Childhood erythroderma may be a manifesta tion of
several dermatoses including ichthyoses (nonbullous
ichthyosiform erythroderma), dermatitis (atopic
dern\atitis, seborrheic dermatitis) and papulosquamous
derrnatoses (psoriasis, pityriasis rubra pilaris) and as an
adverse effect to drugs.
Cllntcat Features
Erythroderma refers to a generalized erythema usually
with, sometimes without, scaling that involves more than
90% of the child's body s urface area (Fig. 26.51 ).
EryU\Toderma is often complicated by thermodysregula-
Fig. 26.49: lichen nitidus: Multiple. small, monomorphlc. tion, sepsis and fluid, electrolyte and nutritional imbalance.
hypopigmented papules over the lower abdomen and shaft Treatment includes addressing the underlying d isease
Of penis and preventing complications. Treatment should be
688 1 Essential Pedlntrlcs
I Pemphlgus Vulgaris
This is the most common variant of pemphigus,
accounting for over 80% cases.
Pemphigus vulgaris is an autoimmune disease,
Chronic Bullous Disease of Childhood
·This is an IgA-mediated blistering disorder, characteriz(•d
by a dermoepidermal split. The condition is seen in
characterized by acantholysis, induced by deposition of children less than 5 years of age. The lesions arc itchy, ll' ll'-C
IgG autoantibodies against desmogleins 3 and 1 present bullae on an erythematous skin. New lesions appe<ir <u ou nd
in desmosomes, which are cell-to-cell adhesion molecules previous lesions resulting in a 'string of pearl' appeara n c
in epidermis. (Fig. 26.53). The lesions are usually grouped nrouncl the
orifices (perioral, perinasal, perigenital or pcriannl). Th ·y
Cllnlcal Features
Patients develop flaccid bullae on non-erythematous skin
(Fig. 26.52). The bulla spreads on tangential pressure (bulla
spread sign) and can be induced (Nickolsky sign). These
rupture easily to form crusted erosions. The usual sites
are scalp, face, flexures and trunk. Oral lesions might
antedate skin lesions in 50% of patients and eventually
80-90% of patients develop oral lesions. Mucosa! lesions
are characteristically painful erosions with ragged
margins.
Treatment
General measures: Counseling the caretakers about course
of disease and necessity of continuing therapy during
asymptomatic maintenance phase is important. Supportive
measures including barrier nursing, skin and mucosa} care
(measures to augment healing, prevent and treat skin
infections), maintaining fluid and electrolyte balance help Fig. 26.53: Chronic bullous disease of childhood: Tense bullae
to improve response to therapy. on erythematous skin In perlgenltal area
Skin Disorders 1689 -
Cllnlcal Features
• C11ta11eo11s lesions: Lesions usually appear in a single
crop. Target lesions which consist of 3 concentric areas
of varying degrees of erythema are characteris tic
(Fig. 26.57). Central bullous lesions are characteris tic
in EM major. Lesions are seen symmetrically on acral
parts especially of upper extremities and on the face.
• Mucosa/ lesions are conspicuous in EM major (buccal
erosions and hemorrhagic crusts of lips).
• Constit11tio11al symptoms are present in EM major.
Most patients are managed symptomatically. In
patients with recurrent EM, suppressive therapy with
acyclovir may be instituted.
I Age
Clinical features
Children
Thin-walled blisters with
erythematous halo; rupture to
form honey colored crusts
(Fig. 26.59)
Infants
Thick-walled, persistent blisters
on bland skin; rupture only after
a few days to leave thin varnish
like crusts (Fig. 26.60)
Any age
Crusted, tender erythematous
lndurated plaque with thick
adherent crusts
Lesions spread without central Lesions heal in center to form Lesions heal with scarring
clearing annular plaques
Lymphadenopathy frequent Lymphadenopathy rare Frequent
Sites of Face, especially mouth and Face, other parts of body Thighs, legs
predilection nose
Complications Post-streptococcal glomerulo- Staphylococcal scalded skin Glomerulonephritis,
nephritls, eczemallzation syndrome eczematization, scarring
Fig. 26.58: Furuncle: Firm, red follicular nodules which discharge Fig. 26.59: Impe tigo contaglosa: Honey-colored crusted lesions
pus and heal with minimal scarring around mouth
Skin Disorders I 693 ..
Treatment
General measures include local hygiene, removal of crusts Fig. 26.61: Stophy1ococcol scolded skln syndrome: Erylt1oma
and superficial peeling of skln in thin sheets
(in ecthyma), rest and limb elevation (for cellulitis). NSAIDs
are used if pain and constitutional symptoms are present.
Topical antibiotics like mupirocin, sodium fusidate and
nadifloxacin are used for localized lesions. Systemic
therapy is required in patients with extensive lesions, in
spreading lesions (erysipelas and cellulitis), and in
presence of constitutional symptoms and lympha-
denopathy. Follicular pyodermas and bullous impetigo
warrant use of anti.staphylococcal antibiotics (cloxacillin
or coamoxiclav) while spreading pyodermas should be
treated with injectable penicillins. For impetigo and
ecthyma, macrolides usually suffice.
Cutaneous Tuberculosls
Cutaneous tuberculosis caused by M. tuberculosis is
classified based on host's immune status as well as route
of inoculation into:
• Lupus vulgaris (Fig. 26.62)
• Scrofuloderma (Fig. 26.63)
• Tuberculosis verrucosa cutis Fig. 26.63: Scrofuloderma: Sinus with mouth showing
• Tuberculids undermined edge and fixed to underlytng lymph node
- 694 I Essential Podlotrlcs
The diagnosis is confirmed by histopathology. Patients presentation depends on the type of leprosy (Table 26.20,
should be evaluated for systemic tuberculosis. Therapy Figs 26.64 and 26.65).
of cutaneous tuberculosis comprises use of four anti-
tubercular medications (isoniazid, rifampicin, ethambutol Lepra Reactions
and pyrazinamide) for 8 weeks followed by 2 agents Two types of acute episodes (lepra reactions) are
(isoniazid and rifarnpicin) for the next 16 weeks. recognized in leprosy. Type 1 reaction (TlR) which
develops in patients with borderline leprosy (BT, BB, BL)
• Leprosy is due to alteration in host CMI. TlR m anifests as edema
The mode of transmission of M. leprae is uncertain but and erythema of pre-existing lesions along with neuritis
possibly nasal droplet infection is important. The clinical which may result in development of new sensory and
manifestations depend on the host immunological motor impairment. Type 2 lepra reaction (T2R, erythema
response. If the host mounts good cell-mediated immunity nodosum leprosum, ENL) which occurs in highly
(CMI), the infection is localized (tuberculoid pole) while bacillated patients (BL and LL) is an immune complex
if the CMI is poor, the infection is extensive with visceral reaction and manifests as several tender, erythematous,
involvement (lepromatous pole). transient nodules on face, flexures and legs. Patients may
The Ridley-Jopling classification, based on clinical, also show neuritis, orchitis, iridocyclitis, arthralgia and
pathological, immunological and bacteriological fever.
parameters, classifies leprosy into:
• Indeterminate leprosy Compllcations
• Determinate leprosy Patients may show the following complications:
- Tuberculoid • Trophic ulcers
- Borderline tuberculoid • Deformities: Claw hand, clawing of toes, foot drop and
- Borderline saddle nose deformity
- Borderline lepromatous • Ophthalmologic complications: Diminished corneal
- Lepromatous sensation, lagophthalmos, recurrent iridocyclitis
Tuberculoid and lepromatous leprosy are stable forms, • Renal involvement
while borderline forms of leprosy are unstable.
Prototype skin lesion is a hypopigmented/ erythematous Investigations
macule/plaque which is anesthetic/hypoaesthetic/ Slit skin smears: Slit skin smears, from the lesions and
nonnoaesthetic. Skin appendages (hair, sweating) on the ear lobules, are stained with modified Ziehl-Neelsen
lesions are reduced and there is epidermal atrophy. The method for acid fast bacilli (AFB). The smears are usually
nerves may be thickened and tender and there may be negative in TI /BT /most BB leprosy and usually positive
associated sensory and motor impairment. The clinical in LLI BL and some BB.
Indeterminate Tuberculold
Skin Disorders
••
involvement
Reactions T1R T1R T1R, T2A T2R
Lepromin +/- + +/-
reaction
Presence of +/- +/- ++ +++
acid-fast bacilli
Fig. 26.64: Indeterminate leprosy: Ill-defined hypopigmented, Fig. 26.65 : Borderline tuberculoid: Well-defined erythema1ous
hypoesthetic lesion on the face plaque with satellite lesions
Skin biopsy: Presence of granuloma (epithelioid cells in For the purpose of treatment, leprosy is classified into
tuberculoid leprosy and foamy cells in lepromatous paucibacillary (PB) and multibacillary (MB) leprosy (Table
leprosy) and nerve involvement are typical.
26.21) and based on this multidrug therapy (MDT) is
Treatment instituted (Table 26.21).
Patient and parents are reassured and counseled regarding Treatment of lepra reactions requires specific treatment
treatment compliance and care of hands, feet and eyes. (Table 26.22).
T•bft 20.21: WHO r1Jcomrneilda11<1na tortremment of T'abfe 26.22: Treatment oi reactions in leprosy
l#ipro§Y In ehll!JrM agfJd 10--15 years Type 1 reaction Type 2 reaction
Ptiuclboclllory Multlbac/J/ary Mifd NSAIDs NSAIDs
D11flnltlon !1 or I~~~ f9slong >5 l~lons Moderate NSAIDs NSAIDs
Duration of (J morrlhs; ta be 12 months; to be Oral corticosteroids Thalidomide·
tMrBpy oompli!tlid In completed in 18 month§ Chloroquine
omonth§ Clofazimine
SuporvJ§!jd Rifamplcln 450 mg Aifamplcin 450 mg + NSAIDs Thalidomide•
clofazlmlne 150 mg Severe
(monthly)
Oral corticosteroids Oral corticosteroids
UmJuptuvlr;od Dapoona Wmg Da~..one 50 mg +
(dtillY) and clofazlmine 25 mg NSAIDs: Nonsterofdal anti-inflammatory drugs
•Thalidomide is a teratogenic agent and avoided in gir1s in the
llltomplr.:ln 10 m!Jlk~; clof1Jtlmlr11:1 1 mg/11.tJ d;,fly, B rrigfl'.g rnonthl'f; reproductive age
dtJp§OncJ 2 mg/k!J
I Sito
clofwd curlaco
(Fig, 26.66)
.. -.... - .
·1 ., • ,
.
...(
..,
,, 1
. . •,'J" ' ,. .•
#
Mofl\JSCUm Contogiosum
Caused b:- a po~irus, patients show multiple, penrly
white, dome--::..llaped p.:ipule:; ";th central umbilirntion
(Fig. 26.68}. Cheesy material c.m b~ ~xprt.>sst.>d from the
lesion. The lesions are ~on .:iny part of the body. The
condition is self-limiting and lesions usually ckar within
a:--ear.
but \1oide:.-pread lesions are~ in p.1tients with alopic
dermatitis and in those who are inmumocompromiscd.
Treatment modalities used include wart paint or
mechanical extirpation.
Hand-Foot-<md-Mouth Disease
The illness is cau_<:ed by coxsackie \irus A 16 infection, with
fero-oral route being the predominant mode of transmission.
It most often affects children between 1 and 10 years of
age during the summer and autumn months. The
inrubation period is 3-6 days. It manifests as an enanthem
oYer the tongue and buccal mucosa, followed by painhil
vesicular exanthem involving lateral aspects of hands and
feet (Fig. 26.69}.
The disease usually runs a self-limiting course of
7-10 days, \\ith a very rare incidence of cardiac and
neurological complications.
Gianotti-Crosti Syndrome
Also krmwn as papular acrodermatitis of childhood, the
conduction is associated with hepatitis B virus and
Epstein-Barr \'irus.
The condition presents as characteristic lesions
(Fig. 26.70} on the face, buttocks and limbs, associated with
mild constitutional symptoms. The mucous membranes Fig. 26.69: (a) Hand-foot-and-mouth disease: Skin lesions:
Oblong vesicles with erythematous halo on palms; (b) Mucosa!
are not affected. The eruption fades with mild desquama-
lesions: Oval. vesicular lesions with erythematous halo
tion in 3-1 weeks.
Dormatophyto1101
k\-:\un~ (Fi~. ~<1.7~) with li•\\'k~1\11111d nl ~111)-\hl t•rylh1•n111.
11\~''\) k~t1I\\~ \\\;\)' ll'\WI.' 1\1\.' \\ llf \'lllycydk 1h_.pll-\llWl\l1ltlllt1 Hlof(IOV
;.\fh.'t' lK'\\\il\~· Thr<•o tWtll'l'il of fungi cnw1c dc!rmntophytoses: Tricho-
phylnn, l\pldl'rmophyton and MkroRporum.
/In/co/ r ooluros
Tlw lnfC'ctlon IA ~·lvrn dl((crcnl nnmes depending on the
sill' nffl•cted. DN~nnlophyl c lnfcction of skin is known as
tliwn corpori:-i, of groin as tinca .cruris, of ha~ds as t~nca
11 rn111111111, of fl•l!I a:-i lin ca pcd1s and of nails as tmea
ungulum. Tlw clnssicnl lesion is nn annular/~rcuate/
polycyclic plilqtw with n clcnr center ;md an achve edge
shnwln8 pnpulovesiculillion ;ind scaling.
'l'i111•11 cn}'itis Three patterns ;ire recognized:
• Nm1-i11fla111111ntory or e11irlemic type en used by anthro-
pophilic organisms ;ind so is responsible for epidemics.
It prcsr•nts ilS nlopcciilc patch, in which hairs break off
Cilsily (Fig. 26.73).
• Itiffa111111nt·ory or kerion: Cnuscd by zoophili c
org;misms nnd so docs not cause epidemics. It presents
as n boggy swelling (Fig. 26.74) from which hair is easily
J ~ -l pluckahll' without pnin. Usually associated with
Ag. 26. 71: Herpes gingi'vostomotitfs: Closed grouped vesicles occipitnl lymphadenopnthy.
on on edematous base which coalesce to form polycyclic • f'11v11s: Caused by T. sc/10c11lei11ii, presents as yellowish,
erosions foul smelling cup-shaped crusts with matting of hair.
Ag. 26.72: Herpes labialis: Polycyclic area of hypoplgmentatlon Fig. 26.73: Tineo capltls: Area of non-scarring alopecla with
and vesicular lesions mlnlmal lntlammatlon with scaling at periphery
Skin Disorders
I 699 -
Candidal intertrigo presents as erythematous, moist,
macerated lesions with a frayed irregular edge with
satellite pustules, present mainly in major skin folds, like
axillae, groins and neck.
Candida! diaper dermatitis is characterized by well-
defined weeping/eroded lesions with scalloped border
and a collar of overhanging scales and satellite pustules.
The lesion begins in the perianal region, spreading to
perineum, upper thighs, lower abdomen and lower back.
Diagnosis
KOH mount shows budding yeasts and pseudohyphae.
Culture is done in unresponsive cases to speciate the
candida.
Treatment
Fig. 26.74: Kerion: Boggy swelling of scalp which drains pus Predisposing factors should be addressed and the area
from multiple openings kept dry. Topical therapy includes imidazoles
(clotrimazole, miconazole and ketoconazole) nystatin
Investigations cream for folds and lotions for oral mucosa. Systemic
The diagnosis is confirmed by the KOH test that shows therapy with weekly fluconazole is given in patients with
fungal hyphae. Culture helps in identification of species extensive disease.
and this is important in patients with tinea capitis. Wood's
lamp may help in diagnosis during epidemics. Pltyrlasls Verslcolor
The condition is cuased by Malasezzin furf11r, a commensal
Treatment
yeast. Patient presents with scaly, perifollicular macules
Tinea capitis Washing with ketoconazole shampoo and with variable pigmentation (hypopigmented, erythematous •
not sharing combs and head wear help to reduce or hyperpigmented). The fine branny scales are accentuated
transmission. Tinea ca pi tis is always treated with systemic by gentle abrasion with a glass slide. The lesions are I
agents; griseofulvin (15 mg/kg/ day of ultramicronized frequently seen on upper trunk (both anterior and
formulation) for 6 weeks is treatment of choice. Longer posterior), neck and sometimes also on proximal part of
treatment (8 weeks) is needed for kerion. Terbinafine upper extremities.
(5 mg/kg/ day for 4-8 weeks) is effective in trichophyton
(noninflammatory) but not in microsporum tinea capitis. Diagnosis
Moroever, use of terbinafine in children is hindered by its KOH mount shows a mixture of short branched hyphae
unpleasant after taste. and spores (spaghetti and meatball appearance).
Tinea corporis Localized lesions of tinea corporis are
Treatment
managed by topical therapy (azoles available as
clotrimazole, miconazole or ketoconazole in lotion, gel and Topical therapy with imidazoles (ketoconazole, 2%) for
cream formulations). Widespread lesions require systemic 3 consecutive days is sufficient in most cases. Systemic
antifungal therapy with terbinafine (2-6 weeks) or therapy with fluconazole is occasionally required in
griseofulvin (4-8 weeks). Due to resistance to terbinafine, extensive and recurrent disease.
itraconazole is being used frequently.
DISEASES CAUSED BY ARTHROPODS
Candldlasls
Candida albicans, a normal commensal becomes pathogenic Scabies
in the presence of predisposing factors including obesity, Scabies is caused by Sarcoptes scabei var hominis and
diabetes and immunocompromised states. Less frequently transmitted by dose contact with infested humans.
other species like C. glabrata may be involved. Patient presents with itchy (worse at night) lesions,
Candidiasis presents as oral thrush, vulvovaginitis, present in a characteristic distribution. The primary lesion
intertrigo, candidal diaper dermatitis or paronychia. Oral is a burrow, a grey thread-like serpentine line with a
thrust presents as soft, creamy white to yellow, elevated minute papule at the end; pa pules and papulovesides may
plaques, that are easily wiped off to leave an erythernatous, also be seen. Secondary lesions consist of pustules,
eroded or ulcerated surface. The lesions are seen on buccal eczernatized lesions and nodules. Lesions are seen in webs
mucosa, tongue, palate and gingiva. of hands, on wrists, ulnar aspects of forearms, elbows,
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py1Jd1 rn111 ol rwr1 lp. Thoup,h ntlult Ike arc dHficult frJ find,
1
Popular Urticaria
l'npultu 11rllc11du IH due to biles of nrthropods such as
mosqulluc!I n11d fle1\H, An Jnllinl llchy, urticorial wheal thJt
dcvclupr:1 nl the tlltc of bite cvolvc11 into a firm pruritic
pnpult!, whkh pcn1lal!I for sevcrnl dny11. Tile lesion often
hM n cc11trnl hemorrhagic pundum (Pig. 26.76) and may
bll sut·mot111lcd by a tiny vesicle.
Scctmdr1ry lnrccllon, cezcmntization, hyper- and
hypoplgmcnl(lllon, partkulnrly in darkly pigmented
lndlvldunla l\l'c not uncommon. New bites by the sarnc
Fig. 26. 75: (a) lnfontlle scabies: Multiple populovoslculor loolons Npeclea ortcn c1wsc 11 t'ccrudcsccnce of activity in existing
on soles; (bl Infantile scabies: Nodular lesions of gonllalla nnd even healed lculollr:t.
Skin Disorders 1101 -
Ag. 26. 7 6: Popular urticaria: Popule with a cen1rol hemonhoglc Ag. 26.78: Acrodermatitis enteropathica: Sharply demarcated
punctum erylhematous plaque over the perianal area with fissured margins
Treatment Treatment
Prevention of repeated insect bites through use of Oral administration of zinc sulfate or zinc gluconate.
protective clothings, judicious use of insect repellents and
treatment of pets with infestation is recommended. Topical Porphyrfa
steroid-antibiotic combination and oral antihistamines Porphyrias are a group of diseases characterized by
help in reducing pruritus and hypersensitivity reaction. genetic or acquired enzyme deficiencies in the pathway
of haemsynthesis, resulting in accumulation of haem
precursors: 5-aminolaevulinic acid (ALA), porphobilinogen
MISCELLANEOUS DERMATOSES
and porphyrins.
Protein-Energy Malnutrition Based on clinical and biochemical parameters,
porphyrias are classified into:
Marasmus is characterized by emaciation and dry, thin, I. Erytl1ropofrtic porpl1yrin: Congenital erythropoietic
pale, wrinkled skin while kwashiorkor manifests as porphyrin (CEP), erythropoietic protoporphyria (EPP).
generalized edema and areas of hyperpigmentation and 2. Ht•pntic porpl1yrin: Porphyria cutanea tarda (PCT),
occasional desquamation ('flaky paint appearance') vnriegate porphyria (VP), acute intermittent porphyria.
predominantly at sites of pressure and friction (Fig. 26.77). Porphyrias are characterized by extreme photo-
Hairs may show alternate areas of discoloration (flag sign).
sensitivity and blistering and scarring of photo-exposed
Acrodermatitis Enteropathlca areas (Fig. 26.79).
Treatment for all porphyrias includes genetic
This is an autosomal recessively inherited disorder
counseling, strict photoprotection and some specific
resulting in deficiency of zinc transporter protein and
measures (Table 26.24).
resultant defective zinc absorption. The condition is
characterized by the dermatitis, diarrhea, alopecia and Mastocytoses
irritability. Characteristics skin lesions include periorificial
Etiology
sharply demarcated, erythernatous crusted plaques with
fissured margins (Fig. 26.78). Mastocytoses are a heterogeneous group of diseases
characterized by localized or diffuse accumulation of
clonal mast cells in U1e skin and/or in internal organs.
Urticaria pigmentosa is the most common variant
(70-90%) of cltildhood mastocytosis. It may be seen at birth
or appear in the first year of life and is characterized by
itchy multiple, discrete, yellowish-brown hyperpigmented
macules and slightly elevated plaques in a generalized
distribution with a truncal predominance (Fig. 26.80).
Dem\Ographism is present in one-third of patients and in
the first 2 years, pathognomonic Darier's sign may be present.
Diagnosis is confirmed with histological and immuno-
Ag. 26.77: Protein-energy malnutrttion: Generalized, areas of histochemical evaluation of skin biopsy.
hyperpigmentatton and occasional desquamatton ('Haky paint Treatment is directed at alleviation of symptoms
appearance') in an Irritable child (pruritus) with antihistamines and/ or disodium
- 7021 Essential Pediatrics
Fig. 26.79: (a) Congenital erythropoietlc porphyrio: Hypertrichosis over the face: (b) Congenital erythropoietlc porphyria : Hyper.
pigmentation, mutilating scarring
~:-~-· - --- - ----- ·-· Table 26.24: Manifestations and treatment' of porphyrias
L.:-:...:-- -~.._:
Classification
Several subsets of LCH with overlapping features are
recognized:
• Letterer-Siwe disease is generalized form which occurs
predominantly in -~ildren <2 years. '
Fig. 26.80: Urticaria plgmentosa: Multiple, discrete, yellow-brown • Hand-ScJ1ii/ler-Clmstzan syndrome is chronic, multifocal
hyperpigmented plaques over the chest and abdomen form, with peak onset in children aged 2-10 years.
Skin Disorders 1103 . . . .
27
Poisonings, Injuries and
Accidents
Jhuma Sankar 1111
INJURIES AND POISONING abdominal and thoracic structures. The impact of ~au~a
is trnnsmitted widely through the body resultmg_ tn
Nearly ~~ of childhood injurit>s are unintentional or multisystem injuries. Early recognition and aggres~1ve
accidental. Injuries aC\.-ount for 6-10'\, t'f ,\ll childhood management of emergencies like ~irway o?struch~n,
deaths. A signifi.:-.mt proportion of tht.~ ~.hildR'n could hemorrhage including intra-abdominal and i_ntrncrnmal
be sa\·ed, if appropri.:i~ injury prevt-ntion nw.\~Un's Wl're hl'morrhagcs improve survival rat~s after maJor_ trauma.
applied. Rrud tr.:ittk cras.hl:':.', falls, dn1wning, bums ~md Subtle changes in heart rate and peripheral pe~fos10n n~ust
poisoning are tht' lt?ading c.rnses of child death from be looked for, as these are signs of 1mpendrng
injuries. A large proportion (e.g. drnwning, bums, cardiof('spiratory failure. Hypotension is a late sign of
falls) occur in or around the home. The following is a
shock and blood pressure may remain nom1al despite
global resource on intentional injury and its prevention:
::?.5-30% blood loss (Table 27.1).
lrttp://rcr.uw.•l'110. in t/<'ioll'llCt'_i11jury_ 1"t't't'lltio11/c11ild/i11j11 ryl
Blunt injury is common compared to penetrating injury.
world_report/m/
Common\ isceral injuries include contusions, lacer<l tion
or hematomn of liver, spleen, lungs as we ll .1S
ROAD TRAFFIC ACCIDENT~D FALL§
pneumothornx, rib fractures and gastrointestinal tr.1ct
Road traffic crashes are the leading cause of death among injury. Ht!ad injuries, alone or associated with mult :ple
children aged 10 to 19 years. India has high rates of road system injuries, are the most severe and cause most d<'aihs.
traffic accidents in the world. falls account for a significant Head injuries also account for disability in children. Bl unt
proportion of visits by children to hospital em~rgencies. trauma in children often results in airway and breath'ng
Seat-belts and child-restraints, helmets, pedestrian lanes, compromise rather than bleeding and shock.
daytime running lights for vehicles, speed limits, laws
against drinking alcohol and driving are a_m?~S !he Management
successful interventions to pre\ ent road traffic mJunes. Children may not cope well emotionally after an accid•.nt.
Severe falls can be avoided by changes in architectural They need to be managed in a calm, child-friend ly
designs, and specially designed child products and environment, preferably in the presence of a pnrcm or
playground equipment. guardian. Initial management during 'the golden huur'
in pediatric emergency includes primary survey . nd 1
Factors Predisposing Children to Trauma
resuscitation by a well-organized team. The gonl of the
Children have a pliable skeleton with less fat and more primary survey is to find and relieve immediate life-
elastic connective tissue, protecting tightly packed threatening conditions. It starts at the injury seem• and
704
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~d:.a:c:5 :...:- " ::: (!(C' :.i.~t:v.
.,, - - _...
Pz:-re:r.tz:J s.-1.- ;:e:-;""?S-)Y.J o:: ex o: =-~·•0!:'.:c; ~--:~ CUC".::::-:::rn..~
morbidity (T;_1l>lcJ 27.2), r~tr5t.i:65m; CTI ce:"...am =:<"?==S c: ..:..::-..;-c~ :=-2 y ttrrtnd"'
1~ ~..e D¢ries:.. c~.:l!:a o sf..cr '.:: ~ .::' ::-:~~rd.!.~
S1•co111l11ry tiflr'INJJ lndud e:; iJ)';!)eMm1~11t a:> per th!!
m1wn1<>nl , "nAMl'l ,J!" (1;ymptmr1:)1 aJle1g)e-,)1 rw!dia=tivrl§/ or ~.:fil..arr.a..~3e faX+'..:s t.o _y.-eoe:-..: ~.s..
f'll:ll llliw:;:;, Ja~I, tlll! i11 1 ;Jlld ~!Y'!lll:? JJ.!i#.finh tn the iJJ~!h) Cm1ken .,,,it.rri ~e:-e &u..~16 c:~....=t:. ?-...=.,..c ~~00.ated
and Jw.1d Ir> 101.~ 1•.x;md1i;11J1m It> iJ~nlify intrathunn.:k , int~ tr~nzttic mjuries r,,.,-nm.; r::igft: ::e =~d b~u._~ of
nbdo111i11;d, and H kJ•lc~ t.;iJ <>r i;k;ull injurie;,, Cuntlt1ued ed.~p,21 ar.d chaTimg ra!a::'e en t:-u::: :_ ~- EI.=.:::-:c.:: Df:r-ies
rcHL1Hdlatl1111 .i11d fl!;1:,:,11JSi>rrHml i.,h11uld prowed CAn oaur rrmn d irect crr-:rtad 0 7 =:- .!:"', ~..: sn.:Il .::s;?
1iJ1t111fhl1H'01Jt;Jy. J<,1cJl11J11)$ic !:Y,mninatit)(J ill Y<J) Yl:',, U.::.t.: (7f H~ >:rike. Drrect cnn.""'·rf C':~. :-_.:s e::=y .::...--:d .:.rit
X·rny, ullral'icm11waphy illld Cr J>GJn t11 defi111: an~fl...nny 5-Jle ·r.rn.md- Tn<:: e:Y.iant ci ~~ ~e-:.6 an =:e T&UL.:0~
nnd nlmormalltic•i,, Jlcx:u ~d iJ%"-~~,mi:nt by ~,ono17aphy iTI of rurrenf, and ro'Jr-x cf ~~L c:..__--.~ ~ <.'.,..,.::_. • t::e 't-cd_:-
lni111Jl.1 CJ 1Nff) may l>c~ IJ1i'_d ul in ddoctin~intra-;,bdvminaJ C urr~f p~mg in the regfo:: o: =.:: ne~ CL1 curse
bJL', dln>S that r an be performC'd w rially at thl.!' bcch,ide,
1
arrllj·thmlz.> and ce.ath. j 155'!:5 ···i~ r..::::-- :-~"!C== itk-e
Mm111x1•1111·11t of l11juri1'1>n:1~uin:-.; a bf)('cialfot mull idfociplinary b ane and tenrl0'1'. s conYe.TI ~are e~e-.:--=:.:::z... e-~ L.cro
,,.,,,,, inv11lvl111~ recJlatric emergency phy!>id ans , th£'rn121 energy and sustain ~n:-e c.a:r-2g e. L."1..~..:.bti.u::?i
a11c•fitlwlilifH, hllfW">llt>, 1>rlh1>pedid.in, pediatrk ink"Tl.'>l-11=-ts 1.njurj, as.50Cia red -,..ifh large ~. C-.C~es ~e .tini.""2!-
nnd tralrwd n11rnl11g p1!n>m111eL Life-thrc:alt.'nin;,; ch e5t direct th_~J injury , chemiraJ pne<..rrru:rni'-K im-m r.d.rm fu l
lnj11ril H, 1•.g. h•111>i1111 p111: urnothorax, flail d u..'!>t, rna,,.:..ivc:
1
chemk.als and Sj'Stemic pd..soning f::-u:n m..W .?.tic.z1 of
hcmolhorax and c:arJ i;u: la mptJrwde 1>huuld be rapidly cyanide and rarbon mmwxide.
llh•ntifJ1!d and marwiw<J. Abdominal blunt injury may
rm111lt Jn <'0111111,lorlf1, h emalomai; or laceration of w lid Clauification of Sums
organH. Suitable an;dgct~ic medication is titrated to
alli!Viillt• p;tin n11d anxiety. Availability ,,f cmc:rgl'llcy Thermal burns may be sc.alds (cau...~.d ITT- ho.! li~d C::"
nwdkal t>1•rvin·H, tn111i,port ''Y"'lerm; and advanced trauma £.team), contact bums (contact \ \; th ho! -obt~): flame
fncililic•r> har> n•rrnltc-d in H i)~nificant reduction in accident bums, chemk.1] bums (exposed to strong arids or alk.J li' )
rnlnfl•d 11111rt,illty in dt!V<:lopcJ c:ounlricr;. f'ulytrauma may or electrical. Based on depth, burns are d .cs....uied a_.;;:
haVl! rilgnifirant pi.ydu1logkal and i;1Jcial impact on the 1. First degree or superficial burns conf.ned to the
Jcvcloplng brain anJ reflult in cons iderable morbidity. epidermis. Characterized as erythem.atous, painful .and
PHychologkal and ttodal support, during n..'Susdtation and dry bums. They heaJ \•.rithin a v•.-eek not le.anno .J.m-
nftcrwor<.li>, it.1 important. scar behind. " ..
BURNS, ELECTRICAL AND INHAlATIONAl INJURIES 2. Second degree or partial thickness bums im·oh·e p3rt
of the dermis, and are characterized b\· en-them.J.h,us,
Wl 10 ('SlimalcH <tpproximately 10% of all unintentional moist and painful bums. (a) Superficial: T;ke less than
Injury rl'lah:J dl•alhH arc Jue lo fire related burns. Children 3 weeks to heal; (b) Deep: Take more than 3 weeks to
arc at· hlKht:r rhlk u( d1!alh from burns with 3.9 deaths per heal and leave scars.
3. Third degree or full thickness bums damage the full bums chemical burns and inhalational injury; and (v) burn
I '
thickness of dermis. These are characterized as leathery, patients with concomitant trauma.
dry and insensate burn. They cannot regenerate The goals of resuscitation and early management are:
themselves without grafting. (i) adequate fluid replacement; (ii) correction of hypoxia
The "rule of nines" for calculating the surface area of and ventilatory disturbances; (i i i ) prevention of
bum is not applicable to children <15-year-old. The Lund hypothermia; (iv) adequate control of pain and anxiety;(v)
and Browder chart can be used for the same. A practical wound care; (vi) nutrition, and (vii) supportive care. IV
approach is to consider the child's palm together with access is established with the peripheral cannula and may
fingers as representing 1% of total body surface area be performed through bum-injured tissue, if required.
(TBSA). The risk of mortality from burns covering 30% of Children with > 10% burns should have urinary
body surface area is -50% and that with more than 50% catheterization to titrate fluid resuscitation.
BSA is -100%.
Flrtid replacement: The goal of fluid resuscitation is to
replenish the fluid loss and to restore and maintain
Rrst Aid
perfusion, tissue oxygen delivery at optimal levels in order
Fire injuries: At the scene of fire, the child should be to protect the zone of ischemia in burnt tissues without
wrapped with a blanket or coat; attempt is made to overloading the circulation. Monitoring urine output and
extinguish the flames by rolling the victim on the ground. a nasogastric tube for continuous suction to prevent emesis
Running with clothes on fire should be avoided. The and aspiration are essential. The adequacy of fluid
victim is rescued to a safe airy place away from the fire to resuscitation is based on urine output, which should be
prevent exposure to gases like carbon monoxide and maintained above 1 mL/kg/hr in infants and young
cyanide. In the case of minor bums or scalds, pour cold children. The Parkland formula estimates the amount of
water, apply cold-water soaks or submerge the burned fluid to be replaced over 24 hours as follows:
portion immediately in cold water. Application of grease,
Volume of Ringer lactate (mL) = 4 mL x weight (kg) x %
soda, oil, powder, butter, toothpaste or herbs should be
TBSA bum
avoided. The wound is covered with clean sheets of sterile
dressing and the patient wrapped in a blanket or foil. In addition, the child requires maintenance fluid
Management of patients requires assessment of the extent therapy. Half of the resuscitation volume should be given
of injury, including surface area, depth and cause of bum. in initial 8 hours and the other half in following16 hours.
Potassium is administered after normal kidney func tion
Electrical injuries: The power supply should be switched
off. Using a nonconductor material (dry wooden stick or is shown. Subsequent fluid management should account
for ongoing fluid losses (Fig. 27.1).
dry cotton clothes), the victim is pulled from the electric
source. The surface injury may be smaller and is often not Analgesia: Adequate control of pain is an essent ial
• indicative of the extent of injury to deeper tissues. Children component of bum management; opioids are commonly
should be monitored for arrhythmias, ongoing myolysis, prescribed.
and secondary organ dysfunction. Wound care and topical tlterapy: Adequate wound care
Inlialational injury: Children with inhalation injury may and topical therapy result in healing of first and second-
require to be intubated and provided supportive degree bums, without need for skin grafting. The most
ventilation. Pneumonitis peaks after 3-5 days of injury. commonly used topical agents are 0.5% silver sulfadiazine,
High blood levels of carboxyhemoglobin suggest carbon
monoxide poisoning. Inhalation of 100% oxygen shortens
the elimination half life of carbon monoxide from 4 hours
(4 mUkg x % BSA burn) (Ringer lactate)
to 40 minutes, and is thus recommended . Cyanide Plus
poisoning can occur when significant quantities of plastics Maintenance (5% dextrose & Ringer lactate)
are burned. The antidote, hydroxycobalamin, infused at
Initial 24 hours
a dose of 70 mg/kg IV, binds with cyanide forming
cyanocobalamin that is stable and excreted in urine. Amyl Half of resuscitation volume in first 8 hours
nitrite and sodium nitrite may induce methemoglobinemia
and are not recommended.
Other half In next 16 hours
I
Subsequent
therapy ,
Hospltallzatlon -
Maintenance
Minor burns can be treated at home with topical Plus
ointments. Indications for inpatient care include: (i) third- Hourly ongoing loss calculated as
(25 + % BSA bum) x Total BSA
degree burns at any age group; (ii) second-degree burns (N/5 In 5% dextrose)
involving more than 10% TBSA; (iii) burn injuries
involving the face, hands or genital areas; (iv) electrical fig. 27.1: Outline of fluid resuscitation In burns
Poisonings, Injuries and Accidents I 101.
0.5% silver nitrate and mafenide acetate. Application use of life jackets, fencing around swimming pools,
of silver s~lf~diazine is painless and has a soothing covering water hazards and prompt first aid.
effect, restricting fluid and heat loss from burn surface.
However, it can cause skin rash, leukopenia, and thrombo- CHOKING AND SUFFOCATION
cytopenia. Silver nitrate is not an effective antibacterial
agent because of poor penetration of the burn eschar. The Choking, suffocation and strangulation are important
medication can cause hyponatremia, hypokalemia, causes of unintentional injuries, especially in infants.
hypochloremia and hypocalcemia. Mafenide acetate Complications include anoxic brain damage and
penetrates the bum eschar effectively; its application may esophageal perforations. Food (chiefly nuts), latex
be painful and associated with skin reaction and metabolic balloons, toys, lids and small containers are commonly
acidosis. involved in choking, while suffocation is commonly seen
in a crib, waterbed or with playground equipment.
Daily dressing changes are required; moist exposed
Ingestion or inhalation of button batteries is dangerous.
burn ointment (MEBO) is promising. Treatment for small,
Most batteries pass through the alimentary tract, but
deep second-degree bums has two components: Excising
occasionally are impacted in the esophagus or cause
the bum wound before it is infected and covering the
gastric erosion. Batteries have also been inserted into the
excised wound with synthetic or biological wound
nose. Ingested small coins are usually passed safely but
dressings. For circumferential burns of the chest, abdomen
may became impacted and require surgical intervention.
and extremities, decompressive escharotomy need to be
performed. Prevention strategies include enforcing regulatory
standards for baby and child product design and
Nutrition: High caloric and protein intake are crucial for manufacture, appropriate labeling and parental education.
survival and recovery. Caloric requirement in children
with burns is estimated as follows: POISONING
Infants: 2100 Kcal/m2 + 1000 Kcal/m2 bum surface area Acute childhood poisoning is a common and challenging
Children: 1800 Kcal/m2 + 1300 Kcal/m2 bum surface area pediatric emergency. Children are susceptible to
Adolescents: 1500 Kcal/ m 2 surface area and bum surface area poisoning because of their curious and exploring nature,
Adequate protein intake (2-3 g/kg body weight) and and propensity to put virtually everything in their mouths.
supplementation of trace vitamins and minerals are Common poisoning agents in high-income countries
necessary. Whenever feasible, particularly in children with include pharmaceuticals, household products and
less than 15-20% bums, nutrients are given enterally. Tube chemicals; in low and middle-income countries, pesticides,
feeding is started on the first day of admission with rapid kerosene, cleaning agents and pharmaceuticals are
advancement towards intake goals. Parenteral nutrition commonly involved. Majority of poisonings in children
is considered in children with extensive burns, inhalation <5 years of age are accidental, while in older children and
injury or prolonged paralytic ileus. teenagers, these are largely intentional.
Supportive measures: Assessment of physical abilities and Clinical Approach to Child with Suspected Poisoning
enabling a full range of joint movements by physical and
occupational therapy and play therapy is encouraged. The initial approach includes stabilization and rapid
assessment of the airway, breathing, circulation and
DROWNING AND NEAR DROWNING mental status. After initial assessment and s tabilization
of vital signs, general physical and neurological
Drowning is an asphyxial death from submersion or examination is done. Physical examination may show
immersion in liquid. It is the leading cause of injury related pallor (hemolysis), cyanosis (methemoglobinemia) or
death for young children under 5 years of age. Drowning icterus (hepatotoxic agents, hemolytic agents) . Acidotic
rates in low-middle income countries are 6-time higher breathing suggests poisoning due to alcohols, salicylates
than in high-income countries. Risk factors for drowning or agents causing hypotension, hy poxia or seizures.
include residence in densely populated areas with large Tachycardia or tachyarrhythmia may point towards
amount of open water, young age, male sex and those with sympathomimetic and anticholinergic agents, while
conditions such as epilepsy and autism. While drowning bradycardia and bradyarrhythmia suggest toxicity with
is most frequent in natural bodies like ponds, lakes and digitalis and cholinergic agents. Oral cavity examination
rivers, drowning in swimming pools and bathtubs is may reveal signs of caustic ingestion such as excessive
increasing. salivation and swallowing difficulties or indicate a poison
Management includes immediate resuscitation and by its odor. Characteristic features with commonly
transfer to a tertiary care facility. In case of death due to reported poisoning agents are shown in Table 27.3.
drowning, parents need to be provided psychosocial Often a particular poison produces a constellation of
support, as it is difficult to cope with the unexpected death. features (toxidromes) involving various organ systems
Successful interventions to prevent drowning include the that confirm the likely diagnosis. A history of vomiting,
- 708 Essential Pediatrics
I
Oral burns Corrosives
Gum lines Lead, mercury, arsenic, bismuth
Odor
Bitter almond Cyanide
Acetone lsopropyl alcohol, methanol, salicylates
Alcohol Ethanol
Garlic Organophosphates, arsenic, kerosene
diarrhea, excessive sweating or salivation, seizures and in a child with suspected poisoning should J11 cl11d1·
presence of meiosis, coma and respiratory failure indicate vomitus or gastric aspirate, and urine nnd IJ)ood
anticholinergic (organophosphate) poisoning, while the specimens. Simple bedside tests help in management oml
presence of mydriasis, dry mouth, seizures, sensorial monitoring of these patients ('fable 27.5).
alteration and hypertension may point towards poisoning
or overdose with cholinergic compounds (Dha tura, Management
atropine or tricyclic antidepressants) (Table 27.4). Emergency cardiorespirntory stabilization Is the priorily
and should precede diagnostic tests. While the patient h
Laboratory Evaluation being stabilized, a member of the team should contact till'
Diagnosis of poisonings is chiefly clinical and quantitative National Poisons Information Centre (NPJC) nt AllMS1
estimation of most toxins is usually not possible or New Delhi which has an emergency helpline avallal>l•l
delayed. Laboratory evaluation is used to support the 24 x 7. Based on the information provided, ndvlcc on
clinical diagnosis. Quantitative estimation of selected diagnosis and management of the child or adult pntlent ls
agents, such as heavy metals, salicylates, some provided and the poisoning is recorded in the Nnllonnl
anticonvulsants, digoxin and paracetamol is available at Database. Helpline numbers arc 1800-116-'J 17, 011·
the toxicology laboratory at the All India Institute of 26589391, and 011-26593677
Medical Sciences, New Delhi as well as a few private http://www.aiims.edu/aiims/departme11ts/pliar111acolosy/Nl'IC/
centers in the country. Samples for quantitative assessment home.htm
Poisonings, Injuries and Accidents
1109 -
Principles of management of patients with poisoning should be optimized to maintain adequate gas e.,xchange
include: (i) initial assessment and rapid stabilization of and hemodynamics, taking care to avoid nosocomial
airway, breathing and circulation (basic life support) and infections.
supportive care, (ii) decontamination, (iii) enhancement Circ11latio11: Causes for cardiovascular instability in
of excretion, and (iv) administration of antidotes. These poisoned patients include decreased systemic \'ascular
are discussed below. resistance, myocardial depression (tricydic antidepres.,i.nts,
.
calcium channel blockers) and arrhythmias (digoxin,
Basic Life Support tricyclic antidepressants). Priority is given towards
Ainoay and breatlting: Early elective intubation is optimization of preload before using vasoacti\'e agents.
preferred in patients with high risk of aspiration and In hypotensive patients, it should be remembered that
progression to respiratory failure. Rapid sequence patients are often not hypovolemic; aggrl'Ssivc fluid
intubation is preferred, due to potential loss of protective resuscitation can, therefore, lead to fluid overload. If
airway reflexes and expectation of a full stomach, with hypotension persists after 1 or 2 st<rndard crystalloid
risk for aspiration. Specific indications for intubation boluses, infusion of a direct acting vasopressor, such as
include failure to maintain patent airway due to CNS epinephrine nnd norepincphrine, is preft•rrL'<i. Arrhythmins
depression or increased secretions; respiratory failure cnused by agents that block fast sodium chnnnels {tricyclic
(hypoxemia or hypercapnia) and severe pulmonary edema antidepressants) are managed with sodium bicarbonate
(salicylates). Establishment of airway may be diffi~ult in therapy.
children with poisoning due to caustics and up~er airway
burns and/ or angioedema. Adequacy of breathing should Supportive Care
be assessed by respiratory efforts, chest excursions, air The goals of care include post-stabilization care and
entry, and oxygen saturation. Mechanical ventilation monitoring for complications and organ dysfunction.
. . 110 I Essential Pediatrics
Convulsions may occur due to hypoglycemia, hypoxia, Pulmonary edema is non-cardiogenic and occurs with
cerebral edema, direct effect of toxin on the central nervous substance abuse (heroin, cocaine) or with aspirin overdose.
system, and hypo- or hypematremia. Seizure control is Treatment comprises of administration of 100% oxygen
achieved through administration of benzodiazepines and positive pressure ventilation, if required. The use of
(lorazepam 0.1 mg/kg IV, midazolam 0.15 mg/kg IV, frusemide and atropine (for organophosphate poisoning)
rectal diazepam 0.2-0.5 mg/kg/ dose). Status epilepticus may be helpful.
is managed as per standard protocol. Pain is common with snake or scorpion bites and with
Acid-base abnomra/ities are commonly observed with ingestion of corrosives. Analgesics, narcotics (if no
alcohols, salicylates and iron toxicity. The emphasis is respiratory /CNS depression) and local anesthetics are
directed at the underlying etiology rather than excessive often required.
use of sodium bicarbonate. Nausea, vomiting and upper GI bleeding may be observed
Electrolyte aud metabolic abnornrnlities are anticipated ~i~h i.ngestion of corrosives or drugs causing gastric
in poisoning with drugs such as digoxin, beta-blockers, 1rntation, or due to stress of illness itself. The use of
insulin and potassium chloride. Administration of antiemetics, H 2 receptor antagonists and proton pump
antidotes, if applicable, and correction of the underlying inhibitors should be considered.
abnormality is important. Decontamination or Removal of Unabsorbed Polson
Hypotlrennia is observed in poisoning with narcoleptic Decontamination is an important step that helps reduce
agents such as chlorprornazine. Management comprises further absorption of the poison. The method varies
of keeping the patient warm, administering pre-warmed depending on the 1JT~ and route of exposure, patient age
IV /nasogastric fluids and monitoring for complications and general cond1hon, and the time elapsed since
of hypothermia, e.g. hyperglycemia and disseminated poisoning. However, decontamination should not be
intravascular coagulation. routinely employed for every patient.
Poisonings, Injuries and Accidents 1111 -
vennal and OClllar decontaminatio11: Dermal and ocular of gut of a child with ingestion of heavy metals, iron,
decontamination begin with removal of any contaminated sustained release or enteric-coated tablets and drug packets.
clothing and particulate matter, followed by flushing of Careful attention should be paid to assessment of the
the affected area with tepid water or saline. A minimum airway and abdominal exam before initiating WBI, and it
of 10-20 minutes of flushing is recommended for most should never be done in a patient without bowel sounds
exposures, although some chemicals (e.g. alkaline or signs of obstruc~io_n or ile~s, or withou~ a protecte.d
corrosives) require longer periods of flushing. Dermal airway. WBI is administered via a nasogastnc tube and 1s
decontamination should include thorough cleansing with continued until the rectal effluent is clear.
soap and water especially in case of organophosphate Syrup of ipecac or use of other emetics is no longer
poisoning. Water should not be used for decontamination recommended as the amount of poison removed is highly
after exposure to highly reactive agents, such as elemental variable and the outcomes do not seem to improve with
sodium, phosphorus, calcium oxide and titanium administration. Induced emesis is also contraindicated in
tetrachloride. infants, comatose patients, and in children with corrosive
Gastrointestinal decontamination: GI decontamination and hydrocarbon ingestion.
strategies are most likely to be effective, if employed Surgical decontamination coml'.'rises of endosc~l'.'ic
within the first hour after an acute ingestion. However, removal of toxins in case of ingestion of large quantities
even rapid decontamination with activated charcoal will, of the toxin or substance (body packers) or lethal amounts
at best, bind -30% of the ingested substance. Of the
of heavy metals refractory to WBI.
methods of GI decontamination, only activated charcoal
and whole-bowel irrigation (WBI) are of clinical benefit. Enhancement of Excretion
Gastric lavage may be employed for patients who arrive
within 1 hour of toxin ingestion. Following insertion of a
The technique of enhancing excretion is useful only fo~ a
large-bore orogastric tube (preferably 28 Fr in infants and few toxins where prolonged exposure can result m
36 Fr in older children) into the stomach, the gastric hemodynamic and respiratory compromise or organ
failure. Commonly used methods for enhancing excretion
contents are aspirated and washed. Child is kept in lateral
decubitus position with head end lowered. Contra- are described below.
indications to gastric lavage include unprotected airway, Urinary alkalinization is used for enhancing excretion of
ingestion of corrosive substances or hydrocarbons, and weak bases and acids, respectively. Alkalinization is
patients at risk for GI perforation or hemorrhage. accomplished by continuous infusion of sodium
Complications include pulmonary aspiration, respiratory bicarbonate, aiming for urine pH of 7.5-8. This procedure
compromise, mechanical injury or perforation of is used to enhance excretion of weak acids, e.g. salicylates,
esophagus, and electrolyte imbalances. There is limited isoniazid, phenobarbitone and methotrexate. Sodium
evidence to suggest that its use improves clinical outcome, bicarbonate is given at a dose of 1-2 mg/kg in one liter of
so gastric lavage should not be considered unless a patient N/5 normal saline and infused at a rate of 0.5 to I liter per
has ingested a potentially life-threatening amount of hour until desired pH is achieved. Serum pH should be
poison. closely monitored, since pH >7.5 is potentially dangerous
Activated charcoal is a potentially useful method of GI for cellular function. Acidification of urine is not advised
decontamination. Charcoal is activated by heating to because of associated complications like acidosis,
extreme temperatures, which lead to creation of extensive hyperarnmonemia and rhabdomyolysis.
network of pores, providing large surface area for
Forced diuresis in order to ensure urine flow -5 mL/kg/
absorption. Charcoal is most likely to be effective when
given within 1 hour of toxin ingestion. It adsorbs almost hr facilitates drug elimination. Brisk diuresis reduces drug
all toxins except common electrolytes, iron, mineral acids or concentration in distal tubules a nd decreases the
bases, alcohols, cyanide, most solvents, most water insoluble concentration gradient, reducing chances of reabsorption
compounds (hydrocarbons), pesticides and lithium. The dose and enhancing elimination. Diuresis is usually combined
of activated charcoal is lg/kg in children or 50-100 gin with urinary alkalinization.
adolescents and adults. A patent and stable airway must Hemodialysis is effective in removal of substances having
be ensured before administering activated charcoal. Its use the following properties: (i) low volume of distribution
is contraindicated in patients with intestinal obstruction, (<1 L/kg), (ii) low molecular weight, (iii) low degree of
ileus, peritonitis and corrosive ingestions.. . . protein binding, and (iv) high degree of water solubility.
Whole bowel irrigation (WBI) involves mstilhng large Toxins removed by hemodialysis include barbiturates,
volume of polyethylene glycol electrolyte solution (PEG- carbon tetrachloride, digitalis, ethanol, ethylene glycol,
ES) rectally or orally to wash out the entire gut. salicylates, theophylline, bromide, lithium and valproic
Recommended doses of PEG-ES are 35 mL/kg/hr in acid. In addition to enhancing elimination, hemodialysis
children and approximately 1-2 L/hr in adolescents. In benefits by correcting metabolic and electrolyte
children, WBI is particularly useful in decontamination abnormalities resulting from ingestion of toxic substances.
-1121 Essential Podlntrloe
Hemoperfusiorr involves circulating bloo~ thro~tgh n However, cf(cctlvu 1111tldotcs 11r(i 1101 11v11lh11Jlo fur t1i11j<,fily
cartridge with large surface area coated with ilchvalcd of pulsonlllg!l, r111d symptorrmtk nrul 911p17~1~tlvu '!:i1ftrH·1ll
charcoal. Hemoperfusion enables removal of substances rcmnlns the 111rtinst11y of 1111111111\{' trt e llL I 11bl1• ?'l.f1 lli:.b
with: (i) low water solubility, (ii) high nffinity for lhc nnlidolcs ui::cd co11i111011ly for· 111r11111g!•rr1(.•fll 111 v11rlt1!1t;
adsorbent, (iii) fas ter rate of equilibrium between ·
po I.su11111gs. A llHI· of 111111111f11tlttrNFJ· of ·i;Jwdfk · 1111tldcJl4-.1;
peripheral tissues and blood, and (iv) low affinity fm• In lmJln Is ll\llintnincd by the Nl'IC.
/
plasma proteins. Toxins eliminated by this technique arc 1111 1://wrow. 11/1111ti.t'1I11/11//1119/t(1·1111tf 11/l'll IP/11/10 r11111r(Jfoy,y/NI I '/
1
carbamazepine, barbiturates and theophylline. 11/1/SSJ'Vf:1/vll / /lg./J //11
Hemofiltratio11 removes compounds with molecular
weight 500 to 40000 RMM, and is used for removal of COMMON POISONINGS
arninoglycosides, theophylline, iron and lithium. ---
--~ -
Exc11a11ge tra11sfusio11 removes poisons affecting the red Hydrocarbon Poisoning
1-lydrocnrbun lngcs llomi ncco1111I for' ~!1 1'• o( arddtnf:•l
1
blood cells, as in methemoglobinemia or arsenic-induced
hemolysis. poisonings 11ml ~25';1,, of d c11liw related lo 1t1w·11llon•1 Ill
Multiple dose activated clrarcoal (MDAC) enhances children <5 ycnrH p,lobllliy. C hildren 111'1· ofh·11 ;wcld•·11tal
elimination by 2 mechanisms, interruption of enterohepatk victims of I IC pnisoni11g 1111 lilcHc prodtr<:1H ilrf' i11appro·
circulation and gastrointestinal dialysis where intestinal prinlcly stored in unlnbckod co11lnlnl•r·n o r drlnkl111;,gl;1 .<i~A ·11
mucosa is used as the dialysis membrane. MDAC is given and arc often nllrnclivc in color or ph•ai>l1 1ll 11 1111·llr111~ lib!
at a dose of 0.5 g/kg every 4-6 hours, until the~ is significnn t furniture polishes. I lydroci11·bo11H arc cnlegorizl'll i11to
decline in serum drug concentrations. Chief complications nliphal'ic (kerosl•ne), arom;1lic (be11zc11c), lial11gN11dl·d
include bowel obstruction and perforation. The technique (cnrbon tetrachloride) and mixed cornpoumlH. Awrnal ir
is recommended for drugs like carbamazepinc, dapsonc,
and hnlogenatcd compounds have prcdomlrwnl f'ffoct on
phenobarbital, quinine and theophylline. lV infusion of
the central nervous system, while aliphatic hydrocarhon <i
intralipid may be used for sequestering fat-soluble drugs
(calcium channel blockers, tricyclic antidepressants) and have risk of nspiralion and pulmonary 1-1yrnplorrw. Tlw
reducing their impact on target organs. most lmportnnl mnnifcslntion of hydrocarbon toxicity b
aspiration pneumonitis via i11 ;1clivalio11 of type fl
Administration of Specific Antidotes pncumocytcs nnd resulting surfactant ddicicncy. llw
Antidotes are substances that counteract the effect of propensity of a hydrocnrbon lo cilusc a Hpiratio11
poisons, and \'\'here available, are of immense utility. pncumonitis is inversely proportional lo ilH vi8cof'lity, a1Hl
I Hydrocarbon Ingestion
I
l
! i
Abnormal chest X-ray
Admit; Oxygen, IV fluids, beta agonists
Monitor respiratory and neurologic status
Normal chest X-ray No steroids or prophylactic antibiotics
discrete or circumferential ulcers; Grade 3a scattered 3-6 weeks after injury, progressively increasing the size
necrosis; and Grade 3b extensive, circumferential necrosis of bougies passed ~ver endosc~pi~ally pla~ed guidewlres,
of mucosa. The risk of perforation and aspiration arc high. Esophnge.11
strictures refractory to dilatation may be surgically
Management corrected by resection and esophageal bypass.
Management comprises of emergency care and supportive
Organophosphate Poisoning
care (Fig. 27.3). Nasogastric tube should not be inserted
and gastric lavage is contraindicated, as they increase the Organophosphates and carbamates are commonly used
risk of injury and perforation. Exceptions are made in pesticide agents and a common cause of poiso~i~'S in
patients with mercury chloride, zinc chloride and phenol developing nations. Organophosphates cause tox1c1ty by
ingestion, as these compounds are associated with severe inactivating acetylcholinesterase, resulting in excess of
systemic toxicity and may be rapidly fatal. Airway nicotinic and muscarinic activity in the peripheral and
protection is a priority as laryngeal edema may rapidly central nervous systems. These agents form an irreversible
progress over minutes to hours and may cause airway bond with and permanently inactivate the enzyme. On the
obstruction and death. Elective intubation might be other hand, carbamates reversibly bind with the enzyme.
required in such cases, or in presence of respiratory
distress or hoarseness of voice. Expertise to perform Clinical Features
emergency tracheostomy or cricothyrotomy should be The symptoms of organophosphate toxicity depend upon
available at the time of elective intubation. There is no the route, duration of exposure, and the absorbed dose.
role for use of intravenous or nebulized corticosteroids or Acute poisoning is characterized by three phases:
epinephrine in reducing the need for intubation. Cholinergic crisis, intermediate syndrome and delayed
neuropathy. The features of acute cholinergic crisis include
Long-ternr management comprises of ensuring nutrition diarrhea, urination, miosis, bronchorrhea/bronchospasm,
and therapy for strictures. Patients are initially kept nil bradycardia, emesis, lacrima tion and saliva tion
orally and managed with IV fluids. Endoscopic grading (DUMBBELS). Some patients show nicotinic features with
helps in planning nutritional support. While patients with hypertension, tachycardia and dysrhythmia, muscle
grade 1 and 2a are allowed oral feeds, those with grade weakness, fasciculations, tremors and hypoventilation.
2b or 3a are fed by nasogastric tube that is inserted by Patients with severe poisoning may present w ith coma
endoscopy. Patients with grade 3b injury receive enteral and respiratory failure which may rapidly progress. Whill'
feeding through gastrostomy; some patients require total recovering from cholinergic crisis, some patients may
parenteral nutrition prior to gastrostomy. suddenly develop respiratory failure (intermediate
Stricture formation is the most important complication. syndrome). Late complications of poisoning include
Dilatation th erapy and surgery are recommended for delayed polyneuropathy and a range of chronic neuro-
prevention and treatment of strictures. Dilatation is done psychiatric symptoms.
I Mild ingestion: Normal oral and upper airways l Moderate to massive Ingestion
Oral, upper airway burns
No evidence of mediastinitis, peritonitis
or hemodynamic compromise
(PAM), which facilitates reactivation of acetykholine- 1 8. If tidal volume <6 mL/kg while weaning from mechanical1
sterase. A stepwise approach to treatment of organo- ventilation (pressure support mode), continue to ventilate. :
phosphate poisoning is described in Box 27.1. 9. Sedation with benzodiazepines to combat atropine-
Pralidoxime is not administered in patients with induced agitation.
carbamate toxicity, since patients usually recover within 10. If features of cholinergic crisis recur, treat as above with
24 hours with or without treatment. Since organo- PAM and atropine. ;
phosphate and carbamate poisoning are clinically
indistinguishable, the initial therapy should be as for the recover completely in 3 weeks time or progress to
former poisoning. Since succinylcholine is metabolized by fulminant hepatic failure.
similar cholinesterase enzymes, its use should be avoided
during rapid sequence intubation. Treatment
The initial management of paracetamol overdose is like
Acetaminophen (Paracetamol) any other toxin comprising of gastric lavage (indicated in
Acetaminophen is a widely used analgesic and antipyretic this case) within 4 hours of ingestion and therapy with
available in different strengths, formulations and its antidote, N-acetyl cysteine (NAC). NAC, a precursor
combina tions. Acetaminophen toxicity is the most for glutathione synthesis, reduces the incidence of
common cause of acute liver failure in the western world. hepatotoxicity, if administered promptly. A single
Acetaminophen toxicity results from formation of highly acetaminophen blood level obtained at least 4 hours of
reactive metabolite, N-acetyl-p-benzoquinoneimine ingestion and plotted on the Rumack-Matthew nomogram
(NAPQI). NAPQI is normally detoxified by glutathione, (Fig. 27.4) is used to decide treatment. The normal thera-
but overdose of paracetamol leads to depletion of peutic level is 10-20 mg/ml. The nomogram predicts the
glutathione stores. Free NAPQI combines with hepatic risk of hepatotoxicity at a single point in time, and thus
macromolecules to produce hepatocellular necrosis. The cannot predict hepatic failure during the illness or patient
toxic dose of acetaminophen in children is >200 mg/kg. death. It cannot be used for multiple doses of paracetamol
or after 24 hours of ingestion, and is not useful for
Cllnlca/ and Laboratory Manifestations associated ingestion with opioid or anticholinergic agents.
The clinical manifestations of acetaminophen intoxication A stepwise approach to management of acetaminophen
are described in four stages (Table 27.7). Patients either overdose is described in Fig. 27.5. NAC can be administered
. - ------- - - - · --·-,
r
Stage Tinie after ingestion ·,
·~~·~-----~
Table 27.7: Clinica! stages of a~etaminophen toxicity
Characteristics
.. -i
(SI unlla) lho llHfllll'/i. 'l'lw phyNl ol1,~lr, fovf•l o( Mctl. lb itJ -4%1of th.ct
11MIL 110/niL I. I11 I Jl{,•1lHwlobln i;1m c1•11trntlon, Mt tf fb i!J reduc&J
BOOO 1000 loI) Ju mop,lol>Jn fJ
by cyhJ! Lrlf11ml! IJ'Jr.1 mo > in<Jm•'de 2lu·'l'11 j ne
, t'
I
000 1
600 100
~
i 200
No llopnllo
Cllnlcol and La/)orulory Munlfot f(Jftom
ij
100
00
toxicity Clinical fcatunJHrnngc from atiymptomatic w ith cya~i~
60 10 lo tic vcrc an ox ic tiym plomi; Ii kc lethargy,, s tupor and
40 11clzureH, Tlw patient appc:rirH cya n ow~, which doc""S n'.A
5 rcllpond to HJO'Y,, oxyrcn. The ltcvcnty of symptoms
20 dcpcnc.IHupon blom.J M~ll fb Jevcli;; k-vcls >70'Yo result in
vm1cular collapHc and J ca lh. Arterial blood gas rev~a ls
10 normal J>a02 and low Sp0 2• BeJ Hidc tests, such as the filter
paper lcHI, ~ re wJef ul for Hcrccning; blood is chocolate-
0 4 8 12 10 20 24 colorcd and J oell not turn red on exposure to oxygen. The
dln gnos is is confirmed by multipl e wavelength co-
Hours nllor lnoosllon
oximelry, which also gi ves MctHb levels in blood,
Fig. 27.4: Rumack-Matthew nomogram
Treatment
Blood for acetaminophen levels ot
least 4 hours post-lngosllon
I Management comprises 6upportive care and administra-
tion of me thylen e blu e, at a dos e of 1-2 m g /k g
followed by bolus of 25-30 mL normal saline. The do5<:
•
cnn be repeated nflcr l hr to maximum of 7 mg/kg ow:r
I. Plot on Rumack-Matthew
1
nomogromJ
··-· 24 hours; at higher dosi.lgc, the oxidiz ing action oi
methylene blue exceed s the reducing action of
~ i_~
leukomethylcne blue. Even after resolution of sympto ~,
patients should be observed for recurrences. Patients wit;1
Acetaminophen levels are below
the broken line _!_____
Acetaminophen lovols oro above
the solid lino G6PD deficiency should not receive methylene blue. Otht'r
therapies include ascorbic acid, hyperbaric oxy gen ar.J
exchange transfu sions.
Do not give N-acetylcystelne; [ ; rapy wlthN-ocetylcy-;teln~
stop, If already started
ENVENOMATIONS
Fig. 27.5: Approach to a child with acetaminophen overdose
Snake Bites
orally or intravenously. King's College critcl'in for The highest burden of envcnomntions exists in south and
acetaminophen toxicity are used for deciding refcrrnl for south-cast Asia nnd sub-Snharan Africa. India has the
liver transplnntation: (i) acidemin (serum pH <7.3) nftel' highest number (46000 annually) snake bite-related deaths
adequate fluid resuscitation, (ii) coagulopathy (INR >6), in south /\sin. More than one-quarter of these deaths occur
(iii) renal dysfunction (creatinine >3.4 mg/dL), and (iv) in children 5-14-year-old, mostly in rural areas and during
grade III or IV hepatic encephalopathy. The degree of the monsoon season. The four most important venomous
transaminase elevation is not involved in determining snakes in India nre Indian cobrn (Naja naja), Indian krait
liver transplantation. (Bimgarus cncrule11s), Russell viper (Daboia russelii) and
saw-scnled viper (Ec/1is cari11at11s).
Methemogloblnemla
Methemoglobinemia is a condition where iron (within Clln/col Features
hemoglobin) is oxidized from ferrous (Fe 2+) lo ferric As per WHO, the diagnosis of envenomation is based on
(Fe3+) state, resulting in inability to transport oxygen to one or more of the following: (i) history of snake bite, (ii)
1111.
pr~enc~~f fani marks, (iii) local features such as pain Management
an swe mg at t e site of bite, (iv) systemic monifestations
such as spontan~ous bleeding or neurotoxicity, or (v) if The 'National Snnkeblte Protocol' was developed in 2006
the~ead s.nake is brought for identification. Systemic to optimize the mnnngement of snake bite victims and to
ma estations of snake bite depend on the species of improve outcomes. There is emphasis on the Do's and
snake. Don' ts of snake bite (Table 27.8), especinlly with regard
• C~rdiovascu!ar toxicif'lJ is seen with cobra and viper to tourniquet application, prehospital trentment,
bites an~ includes hypotension, bradycardia, ndministrntion of SAV nnd management of adverse events
arrhythmias and pulmonary edema. associated with its use. Principles of management nre as
• !femotoxic fe~trtres are seen with viper bites and follows:
mclu~e bleeding from the site of bite, spontaneous Immobilizntio11 of the bitten limb retards systemic venom
bleeding from gums, epistaxis, tears, intracranial absorption. Wnlking for >10 minutes is a risk factor for
~leeds, mele.na, hemoptysis, hematuria, and conjunc- severe envenomation. A stretcher, bicycle, cart or any
tiva! and skin bleeds. Cerebral arterial thrombosis is motor vehicle should be used for transport; if none
seen with D. russelii.
available, the patient should be carried (e.g. fireman's lift
• Neu~otoxic f~atr_1res include ptosis, external ophthalmo- method).
plegia, mydnas1s, and bulbar and respiratory paralysis
is seen with cobra and krait bites. Assessme11t: ABCDE approach should be used in all
• Neplirotoxicity is a common manifestation of bites from children presenting with history of snake bite. Detailed
vipers and sea snakes, and includes features of lower clinical assessment and, if possible, species diagnosis
back pain, hematuria, hernoglobinuria, myoglobinuria, should be carried out. One should look for the dues to
oliguria and uremia. severe systemic envenoming as described above. The
• Endocrine features may occur due to infarction of the bitten part is examined for edema, tenderness, pulses and
anterior pituitary following bites of Russell viper. the compartment syndrome. Systemic examination
includes assessment for spontaneous bleeding from the
Laboratory Findings skin, mucosa and internal organs, and neurologic
The diagnostic test used to confirm hemotoxic bites is the examination for ptosis, trismus, ophthalmoplegia, pooling
20 minutes whole blood clotting time. While the test it is of oral secretions, and paradoxical breathing. Some
useful to detect hemotoxic species, treatment with snake children with neurological symptoms may be un-
anti-venom (SAV) should be based on clinical assessment. responsive to painful stimuli, areflexic and show fixed
Steps for performing the whole blood clotting time are as dilated pupils.
follows:
• Use a clean, new and dry test tube Supportive care of victims of snake bite is important and
• Leave a few mL of venous blood undisturbed for 20 determines outcomes. Care comprises of ventila tion,
minutes inotropes, dialysis, administration of blood products,
• The test tube is tipped to see, if blood has clotted debridement as and when required, maintenance of
• Interpretation: Absence of clotting confirms hemotoxic asepsis, and prevention of nosocomial infections. Patients
envenomation (Viperine species) need to be monitored for complications such as respiratory
Other studies such as hemoglobin, hematocrit, platelet failure, acute kidney injury, compartment syndrome,
and leukocyte count, peripheral smear, muscle and liver tissue necrosis, bleeding into internal organs, refractory
enzymes, electrolytes and venous blood gases, and shock, secondary infections and endocrine dis tur-
urinalysis are performed, if indicated. bances.
Do it RIGHT Do NOT
Reassure patient (only 50% venomous snake bites Use traditional first aid measures, such as local incisions or pricks,
punctures or tattooing at the site of bite or in the bitten limb
actually envenomate)
/Immobilize as in a fractured limb; do not block blood supply Attempt to suck the venom out of the wound
GH Get to Hospital immediately Use (black) snake stones
TTell the doctor of any systemic symptoms, such as ptosis Tie tight bands (tourniquets) around bitten li~b
Give electric shock
Apply or instill chemicals, herbs or Ice packs
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1 1
t.achyc..lroi.a; life-thn:>.1h:' nitlg .m.lphyt"I~ i~ r.u~. S1.1ml' hnwrll' nslnn, myoc1Hdl.1l d yll f1111 r tlnn, a rrhythm i<h,
patients show pyrogenic re.1ctions sh.\kins '-' hills. fl.'\'\'r pulmlllll\I')' l'lkmn (t:ard log1•nk 111· non-cn rd loh1•nic), shock
and hypotension) th.1t oa.::ur 1-2 hout'$ ,\ih.'r infu~illl\ or nnd h) P.ot~n~ion. C(implkntlonfl lncludt~ t'l\c1.•phillop.1thy,
serum sickn~ (few_r, Yomiting, di.lrrht:.\, lymph.ld~no· convulsions, nphnsin, lwmlpl1•Ml11, rPrdlrnl hcmorrhagl',
pathy, nephritis, and encephalopathy} 1-1::? days following DIC nnd rcspimtory fnlh1rl' (Tnhle 27.9).
therapy.
Management
At the earliest sign of a reaction, SAV administr,ltion I~
temporarily su spended. Epinephrine (0.01 mg /k~. 1 in M~nngemcnt i~ directed towards providing symptomat ic
l<XXJ) is gi\-en intramuscularly for early nnnphybctic nnd rchef ns specific thc1'ilPY (nnlivcnom) ll'! not nvnilnblc, t1< 1r
pyrogenic reactions. Subsequently patients should f\'Cein~ rt'comm1mdcd for routint~ use. Blood snmplcs nrc taken
treatment with an antihistamine (chlo rplwnirnmine for electrolytes (hypcrknl1. min), li pid profile (low scrum
1
maleate, 0.2 mg/ kg IV) and h ydrocortisone (:? mg/kg cholesterol and triglyccrklt.s with rise In free fatty acids),
1
body weight IV). In patients with systemic e1wenomation, nnd nmylnse, LOH, nnd trnnsnmlnnscs (nll elevated).
therapy \\ith SAV might require to be gh·en for severnl
days until hemos tatic abnormalities persist.
Table ~7.~: Grading severity of scorpion stings ··
OUtcome Grades Cllnlcal features •
Grade I Isolated pain
The mortality rates ha' e varied between 5°/o and 15%,
Among survh ·ors, the main cause of pemmnent disability Grade II Hypertension, sweating, vomiting, prlaplsm,
fever, shivering
is local necrosis. Large areas of skin necrosis necessitate
debridement and grafting whereas destruction of deep Grade Ill Cardlogenlc shock, pulmonary edema, altered
consciousness
tissues might require amputation. ArHtrodesis, chronic
ulceration, osteomyelitis and malignant transformntion Grade IV Tachycardia, hypotenslon with or without
pulmonary edema
are long-term consequences. Cerebral hypoxia from
Scorpion Envenomation
Suggested Reading • CDC. National action plan for child injury prevention. https://
• Murphy K. Management of musculoskeletal injuries. In: Behrman, www . cdc . gov I safechild I pdf Ina tiona !_action_
Kliegman, Jenson, Stanton (eds) Nelson Textbook of Pediatrics, 2Qlh plan_for_child_injury_prevention-a. pd f.
edn. Philadelphia, Elsevier, 2016 pp 366-74. • Katz A, Kluger Y. Caustic material ingestion injuries-Paradigm shift
• World Health Organization. Children and poisoning. http:// in diagnosis and treatment. Health Care Current Reviews 2015;
www.who.in t I violence_inj u ry _prevention/ child I injury/ 3:152.
world_report/Poisoning_english.pdf.
• World Health Organization. World report on childhood injury • Kajala P, Jhavar L, Singh S, et al. Demographic and clinical profile
prevention. http:/ I apps.who.int/iris/bitstream/10665/ 43851 /1/ of children presenting with acute poisoning in a tertiary care
9789241563574_eng.pdf. hospital. lJEP 2011; 3: 55-9.
Chapter
28
Pediatric Critical Care
Praveen Narsaria • Rakesh Lodha
Care for critically ill children has an important role in small sample volumes. Portable X-ray and ultrasono-
improving child survival. In tertiary care hospitals, 5- 10% graphy units are d esirable. In addition to the p rimary
of pediatric beds are reserved for intensive care; higher disorder, it is necessary to ensure nutrition, sedation and
numbers are required, if the hospital has surgical units. effective analgesia and infection control. Communications
In order to optimize resource utilization in resource with the parents is necessary to keep them informed about
limited settings, it is useful to understand the indications the condition of their child, and ensure their trust and
of admission to PICU (Table 28.1). cooperation.
The optimal number of beds in a PICU is &-10. Attention
is given to the layout, ensuring 200-250 square feet area Suggested Reading
per bed, with rapid access to head end for airway • Slusher TM, Kiragu AW, Day LT, Bjorklund AR, Shirk A, Johannsen
management. The unit should have uninterrupted power C, Hagen SA. Pediatric critical care in resource-limited settings:
supply and preferably be air-conditioned. A crash cart Overview and lessons learned . Front Pediatr 2018;6:49.
having necessary drugs and resuscitation equipment
should be available. The unit should have a central ASSESSMENT OF A SERIOUSLY ILL CHILD
monitoring station and space for utilities and storage. A sick child who is non-responsive to verbal and physical
Equipment required are cardiorespiratory and ECG stimuli should be immediately checked for breathing
monitors, oximeters, devices for oxygen therapy, efforts (gasping, apneic) and central pulses (present,
mechanical ventilators, nebulizers, infusion pumps, absent). If the child has abnormal respiration (gasping
weighing scales and enough disposables. The ICU should or not breathing) or has absent central pulses, th en child
have access to laboratory facilities, including blood counts, should receive CPR (cardiopulmonary resuscitation)
glucose and electrolytes, and blood gases that require irnmedia tely.
Further assessment comprises of the ABCDE approach.
,Table 28.1: Indications for admission to the pediatric intensive A stands for ' airway assessment' and should categorize
care unit the airway as 'clear', 'maintainable' and 'not maintainable'.
-
• Hemodynamic instability or shock requiring inotropic support, B stands for ' breathing assess m e nt' a nd includes
e.g. cardiac arrhythmias, cardiorespiratory arrest, severe respiratory rate and effort, abno r mal sounds on
anemia or hemorrhage auscultation and pulse oximetry. C stands for 'circulation
• Respiratory distress requiring .oxygen t~erapy a~d!or assessment' including skin color and temperature, heart
Impending or established respiratory farlure requ1rrng rate and rhythm, blood pressure, central and peripheral
mechanical ventilation pulses, capillary refill time and assessment of end organ
• Altered sensorium due to any cause, including encephalo- perfusion b y mental status (brain perfusion), and urine
pathy, status epilepticus, raised intracranial pressure output (renal perfusion). D stands for ' disability' that
• Acute hepatic or renal failure and complications establishes the level of consciousness b y A VPU pediatric
• Severe metabolic abnormalities, e.g. dyskalemia, dys- response scale or Glasgow Coma Scale and pupillary
natremla, hypoglycemia, diabetic ketoacidosis; acute response to light. E stands for' exposure' wh ere body parts
poisoning are exposed to look for skin rashes or wounds. Features
• Severe infections, e.g. severe malaria, severe pneumonia predictive of a serious illness, particularly in young infants
• Procedures: Peritoneal dialysis, exchange transfusion, ' are listed in Table 28.2. The history should focus on the
central venous cannulation underlying illness. Common investigations include blood
• Postoperative m.onitorlng counts, glucose, electrolytes and arterial blood gases.
721
- 722 Essential Pediatrics
r·· Table 28.2: Common danger signs. - over sternum or forehead for 5 seconds to cause blanching.
The normal capillary refill time is 3 seconds or lower;
Seizure activity
prolongation signifies impairment of microcirculation .
. Excessive, inconsolable cry Another way of determining adequacy of peripheral
Decreased activity or drowsiness perfusion is noting the core-peripheral te?'perature
Increased work of breathing gradient; gradient >5°C indicates hypoperfus1on.
Abnormal sound on breathing Continuous ECG monitoring is necessary in children
Apneic episodes or cyanosis admitted to the PICU. Central venous pressure (CVP) is
monitored by placing a catheter through a large vein into
Cold extremities (particularly in absence of cold environment)
the right atrium; the pressure informs about venous return
Decrease in the urine output and preload. Normal right atrial pressure is less than
Decreased feeding, bilious vomiting 6 mm Hg. Low CVP in a child with hypotensio~ signifies
low intravascular fluid volume. CVP may be increased
Monitoring due to myocardial dysfunction, fluid overload or increased
pulmonary artery pressures. Renal perfusion is assessed
Respiratory by monitoring urine output; output <0.5 mL/kg/hr in a
The patient should be observed for respiratory rate and child with normal kidneys signifies poor perfusion.
pattern, nasal flaring, use of accessory muscles and color Monitoring of the sensorium and neurologic status also
(Table 28.3). Examination is done for symmetry of air gives information about brain perfusion.
entry, breath sounds and presence of stridor, rhonchi and
crepitations. Respiratory rate is monitored continuously Suggested Reading
by impedance pneumography. Pulse oximetry allows non- • Bronicki RA,Spenceley NC. Hemodynamic monitoring. In: Nichols
invasive measurement of oxygen saturation. While DG, Shaffner DH, eds. Roger's Textbook of Pediatric Intensive Care,
reliable, some conditions lead to inaccuracies, e.g. 5th edn. Lippincott Williams and Wilkins 2016: pp 1120-36.
dyshemoglobinemia (methemoglobin, carbon monoxide • Cheifetz IM, Lee JH, Venkataraman ST. Respiratory monitoring.
In: Nichols DG, Shaffner DH, eds. Roger's Textbook of Pediatric
poisoning}, dyes and pigments (methylene blue), poor
Intensive Care, 5th edn. Lippincott Williams and Wilkins 2016:
peripheral perfusion, increased venous pulsations and pp 686-709.
interference with external light (phototherapy unit,
fluorescent light). Chest radiography and arterial blood
PEDIATRIC BASIC AND ADVANCED LIFE SUPPORT
gas analyses are performed periodically.
Cardiopulmonary arrest in children is much less comm n
Hemodynamlc than adults and usually represents the terminal even t of
Hemodynamic monitoring provides information about progressive shock or respiratory failure rather thil.' a
circulatory status and perfusion of vital organs. The rate primary cardiac cause. The major causes in infants ar;d
and character of pulse should be examined . Blood pressure children are respiratory failure, sudden infant df' ' h
can be monitored manually or by oscillometry. The state syndrome, sepsis, neurologic diseases submersio11 or
1
of microcirculation is assessed by capillary refilling time. drowning and injuries. In contrast to adults sudd->n
Pressure is applied with the index finger or ball of thumb cardiac arrest in children is uncommon. Basic J. fe
~up port (BLS) refers ~o a protocol of procedures perforn~ ~d
-i:able, . - ,,. - . - ·--·- ...... -
-- - 28.3: , - - ~ ---
..- ~ m c.ases of cardiopulmonary arrest to prov d e
Respiratory rates (RR) and heart rates (HR) at car~1opulmonary resuscitation (CPR) with or without
. different _ages ,, devices and bag-mask ventilation till advanced 11fe
•Age, years RR, breaths/min HR, beats/min . support (ALS) can be provided. The major objective'- of
1 30 (22-38) 120 (80-160) CPR are to preserve organ viability during cardiac arrest
and to help return spontaneous circulation.
2 25 (17-33) 110 (80-130)
4 23 (17-27) 100 (80-120) Basic Life Support
~';...":.>t't>...""'-' Ci~'\.tl~ti l.n-.·\irwa\'-o.n.,1thin~ (C-A-U) hn~ cnn usu onci hnnd to 1mpport the lnfont's body and head
~":.~ ~'vmm~'Th.l~,i in 2.\\1~ \t~x'l,\tt- ().f l't'\.'llnt.r~c u,,~ic Lifo nml thll other hnnd to perform chest compression.
$C,.t'f"'rt ti:.' m...iinttin unif\:xrm\ty in CP1' ;;\lg(\flthm ncruss C/u·st co111111·1·s$/oll lt'rf111/q111· /11 lltc cf1//d (1-8 yenrs age)
.ill~~~
Fig. 28.l lndlcntes how the heel of o~e. hand should be
plnccd ovel' lower hnlf of sternum, avoid mg pressure over
xlpholcl, nnd with finger.s lifted above the chest wa·ll· to
r:u.u.ll .l...~··~m~t is d'-'n~ K> C\lnfirm c;irdiac arn~$t so thnt prcvrnt compression of rib cage. Rescuer should pos1t1on
ll.~'-:NXIDf mt'i.\$ttrt~ c,u\ bt' l-t·~un pt\)mptly to l~nnble him/herself vet'licnlly nbove the victim's chest.
int.:tc:t n~Ur\.'>le>~ic sun-iY"L Thl' c~'ml•in"tion of un-
~~n.°'1\-x'n~ .ind ,,~~nt or •lbm).nnal bn.\1thing most
tm;'-:c cl1ildmt 11111/ >R !J<'flrs of nKe: The two-hand ~ethod
for chest compression should be used to achieve an
A.\..--ur.t~~- idrntifi~ (\Huiac "'n~t. P,1lp.\tt{l1' {)f the pulse
<Hkquate depth of compression. This is achieved by
fur it::- a~~ i$ unr-c:-liabh.• a:' tht.' ~ok dNerminnnt of
plncing the lwcl of one lrnnd over the lower half ?f stem um
c.irdi:ic: <nn."':$t. lf tht:> Yictim is \m~spon~\'e, not breathing
nnd the heel of the other hand over the first hand,
rt.\}rm.ill~-. anj the~a~no~~t\$(.l.f lift', lay rescuers should
interlocking the fingers of both hands, with finger~ lift~d
~in CPR: in such 3. settil\~ hto,'\lth ca•e providers shouId
above the che:>t wall. External chest compression in
~CPR unl~ they definitely palpate a pulse \Vithin
Ill se.."'Dnd.'-. children and infnnts should always be accompanied by
rescue breathing. Ventilation is relatively less important
during the first minute of CPR for victims of a~rh.ythmia
induced cardiac arrest than it is after asphyx1a-mduced
CPR should begin with chest compression. Chest
arrest. The lay rescuers should use a 30:2 compr~ss!on
comrre:s.sio11$ are serial rhythmic compressions of the ventilation ratio for all (infant, child and adult) victims.
che.-t that allow blood tlow to \"ital organs (heart, lungs
For one healthc<ire provider, the compression-ventilation
and brain) in an attempt to keep them viable until ALS
ratio should be 30:2 for all age groups and for two rescuers,
(ad,-ancro life support) is aYailable. The victim should be
the compression-ventilation ratio should be 30:2 in adults
aid supine on a hard and flat surface. Adequate chest and 15:2 in infants, children and adolescents. Once an
compression is given by pushing hard, to a depth of at
advanced airway (tracheal tube) is placed, chest
least one-third of anteroposterior dimension or
compressions should not be interrupted for ventilation.
approximately Bz inches (-l cm) in infants and 2 inches
The victim should be reassessed after two minutes. If
(5 cm) in children. The rate should be 100-120
signs of spontaneous circulation have reappeared, chest
compressions per minute, allowing full chest recoil and
compression should be discontinued and only ventilation
minimizing interruptions in chest compressions.
continued till return of spontaneous breathing.
Compression of the xiphoid process should be avoided.
Chest compressiotr i11 ill/ants (<1 year) Airway
Two-thumb technique: The infant's chest is encircled with Infants and children are at increased risk of respiratory
both hands; fingers are spread around the thorax and the obstruction and failure compared to adults, for the
thumbs brought together over the lower half of the following reasons: Smaller upper airway in comparison
sternum, a\·oiding the xiphisternum. The sternum is to adults; large tongue in relation to oropharynx; smaller
compressed with the thumbs and the thorax with the
fino-ers for counterpressure. The two-thumb-encircling \
trauma is suspected, hend and torso should be movi:d n& Mid 1ixR ml1111d (m pn:t;11m µ uf fm,·1y,n body, wf1kf1 I~
n unit and the neck lmmobilir.ed. nimovml, I( vltill>I~·; flHmf 1;v1~·11pitlf!J i~ 11ut rn1111101t:t1dl!d,
OJle" tl1e nirwny: The tongue iH lifted nway from lhtl If the vicllm ill ;rn ln(11nt l//hu 1~ r~·t:.1!1111::-.lw• ""'' fm~ ft•Hllfl~
posterior pharynx to keep the nirway patent. of ilirway nbtilrncUw1, lw Ir e;l1111 1111d t lwi;t thru~t Mt
i. Head till c/1/n lift 111n11e11vcr (Pig. 28.2): If the victim IH pN(OnnNl 1i lI tllH(11n•ly,11 bud y {.' 11~11:~ fJllf I 1( tlll th~· 11dM1t
found unresponsive and has signs of llfo, the 11irway lwc;1mwll u11n·1ip1111Eil111·, If tlw •111 ""' h itll ulder d1Hd (Jf
ls opened by tilting the head back and llfllnK tlw chin. 11<lol,!1ic1•11t, an 11luJ11mln11I tlm1t;I. h ~lvert lly (;t1m<llt1r,
One hnnd ls pl need over the forchead aml lw;id IR b4!hind 1Jw victim till tilt• (1m·l;y1 IJ11dy j1-, i~Y.pdl!:d uul '''
gently lilted back. Simultaneously, the HnKcmi of Iha 1111 tlH! pillf,.:nl lwcwne;; 1J1m•1;pon1:il v1: ( ,tl;tpter 2'J), II tht
other hand arc placed on the lower jaw to lift the chin vlc.llm ht!c;onwn 1111r1•,,JWtltil v1·, airdlopulmmrn r y
to open the airwi\y. This maneuver Rhnuld not be? used, rcRuRcHatlnn 11l11111ld 1)1: h{:y,1rn wlth ;rn <iddltlon;,I
if there is suspicion of trnuma to head nnd /or neck. manc11vcr of du~ckl11~ tlw illrway for fl ti' ford/!fl body ;ifter
ii. fnw thrust (Fig. 28.3): Two or three fingers nre plnccd giving lhc ch1~,,t c:ompn•,,,...f11n and b1·frm: hrnaHw are y)v1:n.
under each side of lower jaw nt its angle to llft the jaw Trnin •c.J hcalthc11n: pmvl1for ,. . J1011ld pt:rform a ton~ue·jaw
lift to look for ob1Hru ctln~ ,,bj~t;ti;,
fJreolhlng
After opening the airway, om: 11l1011ld ch~d; for bn:athlng,
Periodic gat1pin>;, nli;o cn ll<:d ttY,Onu! y,t111pt1, lt> not breath in!~·
If there is effective t1ponta111~ou i; brc:athing without ·vi-
dencc o( trauma, the child iH turn1:d to recovery po~.ltirm,
which helps maintain a p;itcnt airway anc.J prevent',
aspiration.
Components of PALS are: (i) Basic life support; (ii) use of Newborn; >3 kg 3.5-4.0 8
equipment and techniques to establish and maintain effec- Infant 3.5-4.0 8
tive oxygenation, ventilation and perfusion; (iii) clinical
An appropriate sized endotracheal tube is used
and ECG monitoring with arrhythmia detection and
(Table 28.5). Beyond 1 year, the size of the tube is:
management; (iv) establishing and maintaining vascular
access; (v) identification and treatment of reversible causes (Age in year)
Tracheal tube size (in mm) = +4
of cardiopulmonary arrest; (vi) emergency treatment 4
of patients with cardiac and respiratory arrest; and Tubes 0.5 mm smaller and 0.5 mm larger than the
(vii) treating patients with trauma, shock, respiratory estimated size should be available for use. The size of
failure or other pre-arrest conditions. suction catheter is usually twice the internal diameter of
the tracheal tube in mm, e.g. 8 Fr suction catheter for
Adjuncts for Airway and Ventilation tracheal tube of size 4 mm. Cuffed tubes are preferred in
Oxygen should be given to all seriously ill or injured patients with poor lung compliance, high airway
children with respiratory insufficiency, shock and trauma. resistance and large glottic air leak.
During mouth-to-mouth rescue breathings, only 16-17% The depth of insertion of the tube is approximately three
oxygen is delivered, with alveolar oxygen pressure of times its inner diameter. In neonates, the endotracheal tube
80 mm Hg, and optimal external chest compressions is inserted to a depth of:
provide only a fraction of the cardiac output, resulting in Depth of insertion (cm)= birth weight (kg)+ 6
reduced tissue perfusion and oxygen delivery. Ventilation- In children >2-year-old, the depth of insertion of the
perfusion mismatch during CPR and underlying endotracheal tube is:
respiratory disorders causes right-to-left shunting that (Age in years)
reduces oxygenation. Depth of insertion (cm)= + 12
2
Tube placement is confirmed by looking for
Endotracheal Intubation
symmetrical chest rise and auscultating for air entry on
If used properly, this is the most effective and reliable both sides. Auscultation over upper abdomen is required
method of ventilation. The advantages of endotracheal to rule out esophageal intubation. Other markers of proper
intubation are: (i) it ensures adequate ventilation; (ii) reduced tube placement are improving heart rate, color, perfusion
risk of aspiration of gastric contents; (iii) inspiratory time and oxygen saturation. The position of the tube should be
and peak inspiratory pressure can be controlled; (iv) suction confirmed on chest radiograph.
can be done to keep airway patent; and (v) positive end-
expiratory pressure can be provided. However, a skilled Vascular Access
person is required for intubation. Hence, it is recommended During CPR, the preferred access is the largest easily
that bag and mask ventilation should be continued in accessible vein, cannulating which does not require
children who require ventilatory support in the out-of- interruption of resuscitation. Central venous lines provide
hospital setting, when transport time is short or when an secure access, rapid action, higher peak drug levels, and
expert is not available for intubation. Indications for permit administration of drugs that might injure
endotracheal intubation are listed in Table 28.4. peripheral veins (vas opressors, calcium glucona te,
hypertonic solutions like sodium bicarbonate). Femoral
Table 28.4:' Indications for endotracheai ·intubation ~ 1
. vein is the safest and easiest to access (Chapter 29). Agents
Excessive work of breathing leading to fatigue with short half-life such as vasopressors, adrenaline and
Inadequate neurologic control of ventilation, and poor respiratory adenosine act better, if given through central venous
e~rt · access. Catheter lengths of 5 cm in infant, 8 cm in a yormg
Functional or anatomical airway obstruction child and 12 cm in an older child are usually suitable.
Need for high peak inspiratory pressure or positive end Intraosseous access should be tried in patients, if the
expiratory pressure central or peripheral venous assess is not achieved. The
Lack of protective airway reflexes usual site for intraosseous access is upper end of tibia
medial to tibial tuberosity (Chapter 29). Other sites include
For prolonged duration cardiopulmonary resuscitation
the distal end of femur, lower end of tibia above medial
- 12s \ Essential Pediatrics .
malleolus and anterior superior iliac spine. Drugs like · g 4o-60 mL/kg of crystalloids. Dextrose solutions
infusm
adrenuline, adenosine, and vasopressors can be transfused sh ld not be used for initia1resuscitation
· · as they do not
by this route. Samples for chemical analysis, blood ex;~nd the intravascular _volume effe~tiv~ly a~d may
grouping and crossmatching may be taken from these cause hyperglycemia, leading to osmotic dmr:s1s and a
sites. vicious cycle of polyuria and hypovolemia . Hypo-
Tracheal route is not a preferred route of administration glycemia, if suspected or documented, should be managed
of medications even in emergencies. If intravenous or rapidly with intravenous glucose and measures to prevent
intr.-iosseus access is not established, the tracheal route recurrence.
may be used for lipid-soluble agents like lidocaine,
epinephrine, atropine and naloxone. Arrhythmias
Most pediatric arrhythmias are t~e cons.equence .of
Post-arrest Core hypoxemia, acidosis or hypotens10~. Ch1l~ren with
Fever is common after cardiac arrest and should be myocarditis, cardiomyopathy or foll~wmg cardia.c surge!/
controlled aggressively. After return of spontaneous are also at risk of arrhythmia. Drugs m therapeutic or toxic
circulation, hypoxia or hyperoxia should be avoided and doses can cause arrhythmia. About 10% of pediatric
oxygen saturation should be maintained between 94 and cardiac arrest patients have ventricular fibrillation (VF)
100%. Continuous arterial pressure monitoring is done to or pulseless ventricular tachycardia (VT).
maintain blood pressure above the Sth centile. Table 28.6 Bradyarr1iytltmia: Hypoxemia, hypothermia, acidosis,
shows doses for commonly used drugs during resuscitation. hypotension and h ypoglycemia depress sinus node
function and slow conduction through the myocardium.
Fluid Therapy Excessive vagal stimulation, raised intracranial pressure
Ea rly restoration of the circulating blood volume is or brainstem compression may cause bradycardia. Sinus
important to prevent progression to refractory shock or bradycardia, sinus node arrest with junctional or
cardiac arrest. An initial fluid bolus of 20 mL/kg is idioventricular rhythm and AV blocks are u su ally
recommended in shock, and after each bolus, the patient preterminal rhythms. All slow rhythms resulting in
is reassessed. Volume expansion is best achieved with hemodynamic instability require immediate treatment.
isotonic crystalloid fluids, such as Ringer lactate or normal Epinephrine is the mos t useful drug in tr ea ting
saline. Blood replacement is indicated in patients with symptomatic bradycardia, unless due to heart block or
severe hemorrhagic shock who remain in shock despite vagal overtone. For bradycardia due to vagal overtone,
-
Table 28.6: Drugs used duri~g cardiopulmonary resuscitation
Drug Indications Dosage Remarks
rr,,,
I
Epinephrine Symptomatic bradycardia, IV/10: 0.01 mg/kg (1:10,000; 0.1 mUkg) Tachyarrhythmia and hypertension
pulseless arrest ET: 0.1 mg/kg (1 :1000 flush with 1-2 ml occur
of saline); repeat 3-5 minutes, if required
Atropine Bradyarrhythmias 0.02 mg/kg Tachycardia, pupil dilatation may occ ~:
Calcium Hypocalcemia, 1 mUkg IV or 10 (slow push) Monitor heart rate; flush line with sali 1:1
gluconate hypermagnesemia, before and after infusing calcium
(10%, 9 mg/ml hyperkalemia gluconate; avoid extravasation
calcium)
Glucose Suspected, documented 0.5-1 g/kg Avoid hyperglycemia
hypoglycemia
sodium Severe metabolic acidosis, 1 mEq/ kg IV/10 slowly U_se once ventilation is adequate;
bicarbonate hyperkalemia dilute 1: 1 with 5% dextrose
Adenosine Supraventricular tachycardia 0.1 mg/ kg; repeat dose 0.2 mg/kg; M~nitor ECG during dose; give throush
rapid bolus IV/O vein close to heart
Amiodarone Pulseless VF or VT 5 mg/kg IV/10 Monitor ECG during dose
Lidocaine . VF or VT 1 mg/kg IV/10; follow by infusion Monitor ECG during dose
at 2~50 µg/kg/min
Naloxone Opioid intoxication 0.1 mg/kg IV/10/ET Repeated doses may be required
Magnesium Torsades, suspected 25-50 mg/kg rapid push for first Watch for respiratory depression and
two indications; infusion over 30 min hypotension
sulfate hypomagnesemia,
severe asthma tor asthma 1~
' ' . .
ET: Endotracheal; 10: lntraosseous; IV: Intravenous; VF: Ventricular fibrillation; VT: Ventricular tachycardia
Pediatric Critical Care
1121 -
atrop~e is the drug of choice. If no positive or transient Suggested Reading
effect is observed after ventilation and oxygenation, • 2015 Am~ricnn Heart i\srnc!ntinn G uldl'lln e~ Updnl<• for
continuous infusion of epinephrine or dopamine should Caroiopulmonary Rcsusdlntion lmcl Enw1·gcncy Cnrdlovn~<'lllnr
be considered. Care: Part 11: l\.'\Jii.ltrk U.isic Lifo Suppurl nml Cnrdlopulrnon11ry
Rcsusdt,\tion. Circul.1tion 2015; 1:\2: S..'i 19-25.
Pulseless electrical activity: It is a state of electrical activity • 2015 Amcriciln Ht•art Associ111ion Guideline~ Updnlc fur
observed on a monitor or ECG in absence of detectable Cardiopulmonary Rl•suscit... lion nnd cml'l"!ll'llCY C11rd luvnsct1IM
cardiac activity. This is often a preterminal state preceding C.ire: Part 12: Pl-Ji... tric Adv,mn·d Lift• Support. tlrc11lnl1011 2015;
asystol~, ref'.resenting the electrical activity of a hypoxic 132: 5526-U.
and ac1dohc myocardium. Occasionally, pulseless
SHOCK
electrical activity may be due to sudden impaim1ent of
cardiac output with normal ECG rhythm, v.rith heart rate This is an acute syndrome that occurs bemuse of cnrdlo-
increased or rapidly decreasing. Pulses or other evidence vascular dysfunction nnd innbility of circulatory sys tem
of cardiac output are absent and child appears lifeless. to provide adequa te oxygen and nutricnls lo meet the
This state is called electromechanical dissociation. metabolic needs of vital orgnns. Shock, however, i!:i n
Reversible causes of electromechanical dissociation are clinical diagnosis that can exist without hypolens ion. The
best remembered as 4Hs and 4Ts. The 4Hs are severe chief types of shock are listed in Table 28.7.
hypovolemia, hypoxia, hypothermia and hyperkalemia
and other metabolic imbalances, while the 4Ts are tension Blood Pressure Regulation
pneumothorax, toxins and drugs, pericardia! tamponade, A host of neural and Immoral reflexes maintain perfusion
and pulmonary thromboembolism. Treatment of pulseless to vital vascular beds. Neural sympathetic reflexes act vin
electrical activity and electromechanical dissociation is the the vasomotor center and include: (i) bnroreceptors in the
same as treatment of asystole; reversible causes should carotid body and aortic arch; (ii) volume receptors in righ t
be identified and treated appropriately. atrium and pulmonary bed; (iii) chemoreceptors in nortic
Defibrillation: Defibrillation is the asynchronous and carotid body; and (iv) cerebral ischcmic response.
depolarization of a critical mass of myocardium in order Humoral responses are mediated by: (i) adrenal medulla
to terminate VF or pulseless VT. It is successful in cases of through catecholamines; (ii) hypothalamus and pituitary
sudden onset VF having oxygenated normothermic through ACTH and vasopressin; and (iii) ren in-
myocardium without significant acidosis. Larger size angiotensin-aldosterone system.
defibrillator paddles, 8 to 10 cm in diameter, are Bnrorcceptors: Reduction in mean arterial or pulse
recommended in children weighing more than 10 kg to pressure results in decreased stimulation of carotid sinus
maximize current flow. Smaller paddles are used in and aortic arch baroreccptors, and vasoconstriction
infants. One paddle is placed over the right side of the through inhibition of the vaso motor center. Vaso-
upper chest and the other over the apex of the heart. constriction is severe in skeletal muscles, splanchnic and
Alternatively, electrodes are placed in anterior-posterior cutaneous vascular beds, while flow is preserved in
position with one placed to the left of the sternum and the cerebral, coronary and retinal circulation.
other one over the back. C/1c111oreaptors: Hypotension and reduced perfusion
The optimal electrical energy dose to defibrillate is not cause local tissue hypoxia and acidosis, acti va ting
established in children. Available data suggest an initial chemoreceptors that stimulate respiration, induce vaso-
dose of 2 J/kg, second dose of 4 J/kg and subsequent doses constriction and enhance cardiac function.
of >4 J/kg, to a maximum of 10 J/kg (adult dose). Children
>8-year-old or those weighing >50 kg should receive adult Table 28.7: Types of shock
doses of defibrillation. Single shock strategy followed by Type of shock Clinical syndromes
immediate CPR (beginning with chest compressions) is
Hypovolemic Hemorrhage
recommended for children with out-of-hospital or in-
Dehydration due to diarrhea, vomiting,
hospital VF/pulseless VT. After 5 cycles or 2 minutes of
starvation, polyuria, burns, heat stroke
CPR, the rhythm is checked to look for reversion to sinus
Cardiogenic Congenital heart disease, cardiomyopathy,
rhythm. If the rhythm is still VF or pulseless VF, another
cardiac arrhythmias, tamponade, anoxia
shock is given, followed by chest compressions, a dose of
epinephrine and establishing an advanced airway, Distributive Anaphylaxis
provided it does not interrupt the CPR. If after 2 minutes Neurogenic
or 5 cycles of CPR, VF or pulseless VF persists, another Drug toxicity
shock may be given followed by chest compressions and Burns
administration of amiodarone or lidocaine. Simultaneous Toxic shock syndrome
correction of hypoxia, acidosis and hypothermia is Septic shock* Bacterial, viral, fungal
necessary to improve the outcome of defibrillation. •This has components of distributive, cardiogenlc and hypovolemlc shock
- 7281 ~~~~~~~~~~~~_..!E~s~s~e~nt~la~l~P~e~d~la~t~rl~cs!,___--~~~~~~~~~~~------...._
. frock arises from loss of preload. Clues that
lfumoral rccc11tors: Hypotension-induced release of 1-lypovo/~mc ~olemic shock are (i) fluid losses due to
epinephrine and norepi~1ephrine fr01~1 adrenal medulla s~ggest ypo i'ting blood loss, profuse and prolonged
and systl.'mic adrcncrg1c nerve endings Jen~ to vnso- dmrrhea, vom ' . . f h ('') d
. uria or a combination o t ese, or u re uced
constriction and inotropic nnd chronotroptc effects. swcatmg, po1Y · ' · fl 'd d · ·
Release of vasnprcssin from ncurohypophysis cnu~es . k d to vomiting poor appetite or u1 epnvation.
mta e ue ' d emb
vasoconstriction and stimulates free water reabsorptlon . 1 examination shows ry mucous m
Pllys1ca ranes,
' fll d' · · h d
in the distal ncphrnn. absence of tears, delayed capillary re .1 . , 1mlnm1s ~ ~eri-
and poor color. The CVP IS 1ow. vestigations
Rerri11-1mgiotc11si11-t1ldostcro11c syst~m: Reduced. renal p1lera1pttlseS ' . . 1 t d · ·
show high blood urea and creatmme, e eva e unc acid
perfusion results in release of renm fro1~1 the ,iuxta- and small cardiac silhouette on chest X-ray.
glomerular appamtus, that helps convert at~g1ote~1smo?en
to angiotensin I and angiotensin II. Ang1otensm II is a .
Card iogem 'c sliock results from loss of.cardiac contractility.
.
potent vasoconstrictor and stimulates release of aldo- Clues are history of congenital heart d1se~se, r~cent cardiac
sterone, enhancing sodium reabsorption. surgery or d 1·seases 'associated with cardiac disorders
f (e.g.
Duchenne muscular dystrophy), presence o a murmur,
Diagnosis of Shock S3, gallop or friction rub, elevated ]VP and hepatomega.ly.
An early diagnosis of shock or impending shock and its CVP is elevated and chest X-ray may show a large cardiac
appropriate management improve outcomes. Early silhouette and pulmonary edema.
diagnosis of shock requires a high degree of suspicion and
Distributive slrock results from loss of afterload or
knowledge of predisposing conditions. Children who are
febrile, have an identifiable source of infection or are systemic vascular r~sistance .. ~lues on hi~tor_y include
hypovolemic due to any cause are at increased risk. Signs recent allergies or spmal cord mJury. Exarrunation shows
of early shock include tachycardia, mild tachypnea, bounding pulses, well-perfused ski~ and low blood
prolonged capillary refill (>2-3 seconds), orthostatic change pressure requiring large volume of flmd.
in blood pressure or pulse, and mild irritability. Decreased Septic sltock has components of all aforementioned types:
tissue perfusion is identified by change in body temperature Loss of preload, loss of afterload or systemic vascular
(cold extremities) and decreased capillary refill. Vital organ resistance, and loss of contractility. Apart from fever and
hypoperfusion is assumed in presence of oliguria or altered tachycardia, there may be features of decreased perfusion
mentation. Narrowing of pulse pressure is an early finding in form of altered sensorium, prolonged capillary refill
due to reduced systolic and mild increase in diastolic blood >2 seconds (cold shock) or flush capillary refill (warm
pressures. Patients with early septic shock show incre~~ed shock), diminished or bounding pulses, and/ or decre3~ed
peripheral pulses, warm and over perfused extrerruhes, urine output. Hypotension is a late feature. A foci.;s of
wide pulse pressure and hyperdynamic precordium. infection should be looked for.
If shock continues, the compensatory mechanisms are
insufficient to maintain the met~bolic needs ?f ti~sues. Monitoring
Cellular ischernia and inflammation affect brain, kidney Monitoring of patients who are in shock or impending
• and cardiac microcirculation. Tachypnea due to metabolic shock is necessary. Parameters to be monitored are pulse
acidosis leads to respiratory alkalosis. Skin shows features rate and volume, respiratory rate and pattern, tempera-
of reduced capillary refill and mottling. Hypotension, ture, skin color, blood pressure, sensorium., urine output,
oliguria and hypothermia set in. Mental changes include ECG and pulse oximetry. Metabolic parameters incl ude
agitation, confusion, stupor and finally coma (Table 28.8). blood glucose, electrolytes and arterial gases.
Classification Therapy
Recognition and treatment of shock depends upon the Therapy depends on the type of shock. In hypovok 1nic
etiology of shock. shock, replacement of intravascular volume by isotonic
~ ·- Table 2a.e: stage s of shoc k - · ·--T, - -·-, "; -,., ·
Clinical parameter Compensated Uncompensated Irreversible
Mental status Agitation or confusion Drowsiness Unresponsive
Heart rate Tachycardia Marked tachycardia Bradycardia
Respiration Normal or mild tachypnea Tachypnea Apnea
Skin and capillary refill time Increased capillary refill time Very slow capillary return Cold and cyanotic skin
with cold peripheral skin and mottling
Urinary output Adequate Oliguria or anuria Anuria
Blood pressure Normal Hypotension Unrecordable
··- ,,
Pediatric Crltlcal Care 1729 -
t1:uid!$ is t\t.'l.."eS&'lry. In cardiogenic shock, inotroplc support monitoring and are cons idered for intubation and
and n.-duction of afterload by use of vasodilntors is mechanical ventilation.
~net1ciaL
Vasoactlve Drugs
Fll.Jk:i Tl'!erapy Vaso11rcssors (Table 28.9) Dopamine is the first-line
\'"scufor accrss: Large bore IV cannula or catheter is inotrope for mnnaging shock nssociated with high cardiac
pfaC\:~ in u large peripheral vein, e.g. femornl
vein. In older output and low sys tem ic va scular resistance, The
children and adolescents, cannulation of internal jugular, medication increases cardiac output at doses of 5-10 µg/
e.'\.-tl:>mal jugular and subdavian wins can be considered. kg/min. Its vnsoconstrictor effect of dopamine is seen at
Flvi,1$ and lilood 11roducts: The first choice of fluid for the doses >15 µg/kg / minute and follow release of norepine-
acute st-,lge is 0.9% normal s<lline or Ringer l<lctate. Large phrine from sympathetic vesicles, which may not be weJl
Yoltm1e5 o.f fluid have been used for acute stabilization in developed in young infants ( <6 months). Low dose
children ,.,,·ithout increasing the risk of <lcute respiratory dopamine (2-5 µg/kg/min) does not significantly affed
distre&; syndrome or cerebral edema. When fluid require- renal blood flow. Dopamine refractory shock responds to
ment is high, colloids (dex.i ran, gelatin, 5% albumin) may norepinephrine or high doses of epinephrine. Some
~ u~i. Packed red cells should be given at 10 ml/kg, to clinicians prefer using low dose norepinephrine as the first
maintain hematocrit -33%. line agent for warm hyp erdynamic shock. Use of
vasopressors can be titrated to maintain a perfusion
folume of.t1uili~ Nonna! saline or Ringer lactate, 20 mL/kg, pressure, that refers to mean arterial pressure minus CVP,
is inhL--ed rapidly over 5-10 minutes, and titrated with or systemic vascular resistance that ensures adequate
changes in heart rate, capillary refill and sensorium. If no urine output and creatinine clearance.
significant improvement is noticed, repeat boluses of
20 ml/ kg are given. Large volume fluid deficits require Inotropes (Table 28.10): After initial fluid resuscitation,
-IQ to 60 ml/kg and maximum up to 200 ml/kg over first- myocardial contractility needs to be augmented to
hour for replenishing the deficit. In situations where improve cardiac output. Dobutamine and mid-dose
availability for ventilator support and inotropic drugs is dopamine are used as initial inotropic agents in adults,
limited, fluid boluses should be administered cautiously. but children are less responsive. Epinephrine infusion
Patients who do not respond to boluses of 40-60 ml/kg usually works in dopamine or dobutamine refractory
in 1 hour are labeled as fluid refrncton; and should receive shock. Low dose epinephrine is used as first-line choice
inotropic support. These patients require careful for cold hypodynamic shock, i.e. low cardiac ou tput.
Epinephrine
Norepinephrine
Phenylephrine
2-20 µg/kg/min
O.o1-2 µg/kg/min•
0.05-1 µg/kg/min
0.1-0.5 µg/kg/min
D,!02 > 13 >a:
131=132 >a:
13 >a.
a selective
Renal effects, early inotropy needs,
septic shock
Anaphylaxis, cardiogenic shock
Severe vasodilatation, hypotension
lschemia, hypertension
Acidosis from poor perfusion,
ischemic injury
Acidosis, ischemic injury
•
spells
·-
- 730 1!1uumllnl Put1lntrlo1
~------~---------==.:.:!!:!..~~2!.-----------------------~
i-- - ---r,.· <
i'abl~· 20.11: VModllolor i£gtmtn
(//§/(
Drug D~~a()e Sito of EJOllm1 Uno
Nltroprusslde 0.3-7 µg/kg/mln At'tsrlus > volno Aflorlo111..I rocJuotlon Cymlltlo toxlolly, hypotmrnlon
Nltroglycerln o.5-5 µg/kg/rnln Velni:1 > tltl13rlt19 tJrolottcJ tmd ofit,1tlewrJ rntJuollun I fypolom1lon, rfltllh@moaloblnomltt
NUTRITION IN THE CRITICALLY ILL Use of TPN requires monitoring of blood glucose 2-3
Critically .m children are prone to malnutrition, due to times a day; electrolytes and urea twice a week; and
red~ced mtake and accelerated demands, increased weekly biochemistry, triglycerides and blood counts.
~esh~g ~nergy expenditure, proteolysis, and glucose and Complications include catheter-related infections, liver
msu~1~ mtoler~nce. It is essential to provide adequate dysfunction, hyperglycemia, acidosis, hyperlipidemia and
nutrition early m the course of illness in order to improve electrolyte imbalance.
outcomes. The enteral route is preferred, since it is safer
Suggested Reading
and more c?~t-effective than total parenteral nutrition.
~nt~ral nutrition helps maintain the gut barrier, preserves • de Carvalho WB, Delgado AE, Leite HP. Nutritio nnl s upport. In:
Nichols DG, Shaffner DH, ed s. Ro~cr's Textbook of Pcdiiltrlc
md1ge~ous flor~ and prevents overgrowth of pathogens, Intensive Care, 5th edn. Lippincott Willia ms nnd Wilkins ::!.016:
reducm.g the nsk of bacteremia and pneumonia. By pp 1615-32.
preve~ting ~trophy of gut mucosa, resumption of oral • Joffe A, Anton N, Lequie r L, Vnndenncer B, Tjosvold L, L1rst•n 13,
f~eds .1s easier ~uring recovery. Supplementation of Hartling L Nutritional support for criticnlly ill children. Coclmme
vitamins and rnrnerals is also best done by the enteral Database Syst Rev. 2016; 5: CDOOSI~ .
route.
Apart from milk-based feeds, commercial formulae are SEDATION, ANALGESIA, PARALYSIS
available to supplement nutrition. Elemental formulae The goal of sedation is safe and effective control of pain,
contain carbohydratis as oligosaccharides, maltodextrins anxiety and motion, allowing necessary procedures to be
or hydrolyzed cornstarch; nitrogen as peptides or amino performed and to provide appropriate amnesia or
acids; and lipids as oils or medium chain triglycerides. decreased awareness. n\e state of consciousness varies
~~~ lactose or lactose-free diets are available. Feeding is from mild to deep sedation to general anesthesia. In
rmtiated at10-15mL/kg/day and increased byl0-15 mL/ moderate sedation (conscious sedation), consciousness is
kg/ day until targets are achieved. Feeds may be delivered depressed but protecti\·e airway reflexes are maintained
directly into the stomach by nasal or oral routes. Bolus and the child responds appropriately to verbc11 command
feeding is preferred over continuous feeding as it is or to light physical stimulation. Airway is maintained
physiological and requires less expertise to administer. independently and spontaneous 'entilation is ,1dequate.
Small bowel feeds are useful in gastroparesis. Continuous Deep sedation refers to a medically controlled s tate of
feeding is preferred for small bowel feeding. depressed consciousness from which the child is not ensily
Conditions where enteral feeding is contraindicated are aroused but responds purposefully to painful stimuli. The
severe gastrointestinal hemorrhage, recent gastrointestinal ability to maintain airway is impnired and requires
surgery and intestinal obstruction. Complications of assistance; spontaneous ,·entilation m<iy be inadequate.
enteral feeding are intolerance, misplacement of the
feeding tube, esophagitis and esophageal ulceration.
Gastrointestinal reflux can lead to pulmonary aspiration.
Diarrhea may occur because of hyperosmolar formulae,
infection or malabsorption.
The child should be carefully assessed before sedation
for underlying medical problems, medication use, allergies
and time and nature of last oral intake. Monitoring is
important during sedation and following procedures,
including assessment of vital signs, movement of chest
I fl
Parenteral nutrition refers to the delivery of nutrients wall, ECG monitoring and pulse oximetry. Table 28.12
directly into the bloodstream, including amino acid summarizes commonly used drugs for sedation and
mixtures, lipids, glucose, trace minerals and vitamins. -· analgesia and Table 28.13 lists clinical scenarios requiring
These are infused into a peripheral or central vein. A sedation and analgesia. For children on mechanicnl
peripheral vein may be used, if the osmolality of infusate ventilation, continuous infusion of midazolam or
is less than 700 mOsm/kg. For delivery of adequate diazepam is used for better control of ventilation.
calories, central venous access is essential. For infants, Intermittent doses or continuous infusion of fcntanyl or
glucose infusion is started at 5- 6 mg/kg/min and morphine is used for pain control.
increased gradually; insulin may be used, if there is
Neuromuscular Blocklng Drugs
hyperglycemia. Amino acids are begun at 1 g/kg/d and
increased over 2-3 days to 2.5 g/kg/d. Lipids are given The use of neuromuscular blocking drugs is common in
at 0.5 g/kg on day 1 and increased to 2-2.5 g/kg/ d over patients with artificial airway who <UC undergoing
4--5 days. Appropriate combinations can be achieved by mechanical ventilation. Succinylcholinc is the only
considering fluid requirements. In a critically ill child, the depolarizing muscle relaxant available. Non-depolarizing
energy requirement is lower, as metabolism may be drugs are pancuronium, atracurium, vecuronium and
decreased, there is decreased activity due to illness, rocuronium. Short-term indications for these drugs
sedation and analgesia, and growth is lacking. The energy include ainvay instrumentation and invasive procedures.
goal in the initial phase of acute illness is less than for a Long-term use facilitates: (i) mcchanicnl ventilation,
normal child and revised regularly to avoid overfeeding overcoming patient ventilation dyssynchrony, and/or
and underfeeding. ensure high frequency ventilation; (ii) reduction of work
-732
~-·---·-- ...
-..---~~ ··~-- ·---·-~.-~--
Table 28.13: Cllnlca.1~cenarios f_
o !_~a,!lo~ and analge~l.a
Clinical scenarios Examples Sedation strategy
Non-invasive procedures CT scan Comforting alone in older children
Echocardiography Chloral hydrate orally
EEG Triclofos orally
MRI Midazolam intravenous (IV)
Ultrasonography Comforting alone
Procedures associated with low level of IV cannulation Comforting and local anesthesia
·pain and high level of anxiety Phlebotomy
I .
Lumbar puncture
Flexible bronchoscopy
Procedures associated with high level of Central catheter placement Midazolam and fentanyl or morphine IV
pain and high level of anxiety Bone marrow aspiration Ketamine IV or intramuscular
Endoscopy
Abscess: Incision and drainage
lnterventional radiology procedures
lntercostal drainage
Paracentesis
-r... a.1.c: _S> :r., R!ICb2 tw are prepared by pn..x.~ing bfb>e pooh; of ti~nor pl.ls.mo
obtained from whole blood or pla~mnrhere~t~.
Hf!.rid ~ ~.d fqgfer:e., f"z:d cisfti.ecfon
Indications for r~ cell trnnsfu~ion •lr~ listt'd in
~ p-e;--..a.6:rs ~g irr~P- pm::edi:r.5
Table :!S.15.
€:',.sr..re ~O:;n; F'refa ~ t'.) ;:a-~ r!LrUmOO
Tn:m::.jusion (r!raa.rh-bloo,l lo~~ lf p,itient is not Shlbilin.'<-i
Awqrr.e e:'.d rE6yf2! p--c:scnptbn at zr".J:Jidi:;s after 2 bolu..~ of 20 ml/ kg of isotonic cr}~talloids, it is
P~ O""~ rraa:::tc.n CCtiC"Cl.. w~ "rec.Xe guidelines likeh- that the bl°'-'Xi lo.....;s is >30% ,md the p.ltient ~hould
S'/x~iC:e fa HAI reref',.-e ~h blood.
fka;"(h care 2SSCCiatE:d ~J:trcc.iz.: A·.tic ant2cids and ~ Transfusion for drronic '11r.•mid: Olildren with chronic
f'i.o'.f<ers; cfsi~ r~~/ tfie.r.:p/ eq:iprnerrt; st=ri!e Hufds anemia ll!>--Ualh· tolerate hemo-.;lobin le,·els as low ,1s -1 g/ d L
6"'.A""r..E:f.l~~ arid ruria""~; aia:-.ge ..~or ciram Mling Im·estisrationS for the underhing (\\Use of anemia should
e,g;<f ~ r.o..zs; care dcrirrg scctcning; head end at ~ be sen~ prior to instituting t.r,msfusions. Patients arc
efetaf"oo-; o~.ed ~cd"iea! ~; sc.'.ec:5'~ decamamination screened for cardio\·asculnr decompensntion, an
ot g:;t (f£br:e.mr.in. ~.t.a.11fcin, pdJmJXin. r.:.(5tatin) indication for emergfficy transfusion.
ef<xxf;st.ream W.ecticn: Care cJ v-~ ao:ess; use of Teflon Oro ice ofblood group: For red cell trans fusions, the choices
a pr$\JUretT:e:ie came!ers; a-!Oi..d rr.ut"-.Zumen catheters; use
are ba_.;;ed on the principle th,1t the recipient plasma must
t:ar..sy:aret".t dre.<>..si:-~-; rnmlt':'.aJ ""break in. in~o catheter and
~tr~oos f:uting; 2:1/cid TPN catheters fer other infusions
not contain antibodies corresponding to donor A or B
antigens. For plasma and pl,1telet transfusion, donor
Uliri:ary tract infectkJns; WnimaI catheterization; asepsis plasma must not contain A or B antibodies corresponding
durltig insemoo; dese:d drarnge; ea.1Y removal of catheter
to recipient A or B antigens (Table 28.16). Patients who are
RhD negatiYe should receiYe only RhD negative red cells.
The risk of HAI is related to the severity of underlying Ideally, the same blood group red cells that are compatible
fffnes.,., length of PICU stay, iw,-~-Jve monitoring and with the recipient plasma should be transfused.
diagnostic procedures, and indiscriminate use of Quantity of trmrsfusiotr: The quantity of blood
antimicrobials. Almost 90% of bloodstream infections administered depends on hematocrit of the blood unit,
occur in children with central venous lines, 95% of
pneumonia in those on mechanical ventilation and 75% Table 28.15: lncfications for red blood cell transfusion in children I
of UTT in children with catheters. HAI may be caused by Infants
o-:-ganb"Tl'l.S that originate from exogenous sources in the Hematocrit <.20 and asymptomatic with reticulocytes <100000/
hospital or from patient's ov.--n flora. Apart from increased cu mm
duration of hospital stay and cost of therapy, mortality
1.
Hematocrit <30 and requiring oxygen
attn'but:ed to HAI ranges between 10 and 20%. Hematocrit <35 and requiring CPAP or mechanical ventilation;
It is important for JCUs to have infection control heart rate > 180/min or respiratory rate >80/min persisting for
proryams to reduce the risk of HAI. A team of health >24 hours; weight gain <10 g/day over 4 days while on >100
profa~sionals should ensure implementation and CaL'kg/d; or if undergoing surgery
CDmpJiance on part of the PJCU team_ Infection control
Children
activities (Table 28.14) can reduce HAI rates by -50%.
Hemoglobin level S4 g/dl (hematocrit S12) irrespective of
clinical condition
Suggested Reading
Hemoglobin 4-6 g/dl (hematocrit 13-18) with features of
• Jonm r-.i, de Saint Blznquat l , Stamm D, 1.aunay E, Gras-Le Gum
C. H~lthure-associated infection prevention in pediatric intensive hypoxia, acidosis, dyspnea or impaired consciousness
care anits: a tl?View. Eur J Oin Microbial Infect Dis 2012; 31: Malaria with hyperparasitemia >20%
24fs1-W, Features of cardiac decompensation
8lOOD TRANSFUSIONS Table 28.16: Choices of ABO blood groups for red cells,
Blood componenf transfusion is an integral part of plasma and platelet transfusions
treatment for many patients cared for in PICU. Blood Recipient Acceptable ABO group of component
products are prepared from coIIected whole blood or blood group
aphl·n:.-si~ donation. Whole blood units are separated into Red blood cells Plasma Platelets l
red cells (RBC) and plasma and platelet components by 0 0 0,A,B,AB O,A,B,AB
differential centrifugation. Automated apheresis
procedures are used to collect platelets, granulocytes or A A,O A.AB A.AB
plasma, Cryoprecipitate is prepared from a plasma urtit. B 8,0 B,AB B,AB
Ma$ma proteins, e.g. albumin, anti-D immunoglobulins,
IV immunog.lobulins and concentrated coagulation factors AB AB,A,B,O AB AB
- 734 1 Essential Pediatrics
pretransfusion hemoglobin level and patient weight. If the Tabfe 28.18: tndicatfons for transfusion offresh frozen Plasma
hemoglobin level is ~5 g/ dL and citrate phosphate Coagulation factor ~eflciency when individual factor
dextrose red cells (hematocrit 70-75) are used, a trans- replacement is not available
fusion of 10 mL/kg raises hemoglobin level by 2.5 g/dL. Anticoagulant (vitamin K antagonist) related bleeding
If anemia has developed slowly and hemoglobin level is
Severe liver disease with prolonged prothrombin time or
<5 g/ dL, red cell transfusion should be given slowly or in
bleeding tendency
small quantities to avoid precipitating cardiac failure from
Disseminated intravascular coagulation with active bleeding
circulatory overload.
C1 esterase deficiency in hereditary angioneurotic edema
Platelets
Platelet concentrates are prepared from whole blood mL of donor plasma and stored at -20"C for up to 1 year.
donation but these may also be collected by apheresis. The This unit contains 80-100 units of factor VIIJ, 100-250 mg
usual platelet bag (unit) contains 7.0 x 1oio platelets, about of fibrinogen, 40-60 mg of fibronectin, 40-70% of vWF and
50 mL plasma, trace to 0.5 mL of red cells and varying 30% of factor XIII. Indications for use include hemophilia,
number of leukocytes (up to 108). Apheresis platelet units von Willebrand disease and congenital deficiencies of
contain 3 x 10 11 platelets, approximately 250-300 mL fibrinogen or factor XIIL Compatibility testing of
plasma, trace to 5 mL of RBCs and 106-109 leukocytes. It cryoprecipitate units is not necessary but ABO compatible
can be stored for 5 days at 20-24°C. The need for platelet units should be used. Cryoprecipitate is infused at the rate
transfusions depends on the platelet count, bleeding of 1 unit/5-10 kg of recipient weight, over 2-4 hours.
tendency, etiology and setting of interventions like
invasive procedures or surgery (Table 28.17). Risks of Transfusion
The chief risks of blood products include: (i) transfusion
Plasma reactions; (ii) transmission of infectious agents, including
Plasma is prepared from a whole blood donation by HIV, cytomegalovirus, hepatitis Band C viruses, syphilis
centrifugation or automated apheresis. A unit of plasma and malaria; and (iii) bacterial contamination due to
contains 150-250 mL when prepared from whole blood inappropriate collection or storage.
donations. Immediately following collection, plasma
contains approximately 1 unit/mL of each of coagulation Time limit for infusion: There is risk of bacteria l
factors. Coagulation factors V and VIII are labile and are proliferation or loss of function in blood products once
not stable in plasma stored at l-{i0 C. Plasma frozen within they are removed from storage.
8 hours of donation (fresh frozen plasma, FFP) contains i. Whole blood or packed red cell transfusion should
:::0.7 U/mL factor VIII; this may be stored for 12 months begin within 30 minutes of removing from storage
at -20°C. The use of FFP is limited to treatment or temperature (2-{i 0 C) and completed within 4 hours, ii
prevention of significant bleeding due to deficiency of one amb_ient temperature is 22-25°C. In case of h igh
,,f
Mt,lk. .\\ pt\.),._"°"'hn\..~ \m·,,h·\,\ \n \\\\\' d1lldl'\'I\ lm:lmlu
di.~n1..\."tk Pt\'-'\\.hn'\.'~ ;\l\d llwr11l°'\'u\ k \l\l\'l"\'t'lllll111s, S\ 11\\l'
(It whkh m.w h~ cr\tk;1\ 1.w Hfo s;w\11~. It Is im1Hwtnnl to
. '
\:'lb$t'rn~ m1h·c1~''\ ~ll'r\lc p1\'l.'11utk111s dmln~ nwdlcal
pn:)\x"l.lmc ,md disp1.~~ \\'\\St\' '"·tid\'S 11pp1\1p1'1,1lt•lr.
Com!11icati011s: ~h~st compressions mny cause rib and Central Venous Cannulatlon
cnrd1~c dnmngc II\ mfnnts, but arc rnrc, if performed by lmlicatious: Usw1l indications include: (i) inability to es tab·
ex~en~nccd personnel. Uncommon complications of the lish venous nccess in the peripheral circulation; (ii) access
Heunltch m~nc~1vcr, if performed incorrectly, include for drugs and fluids thnt require central administration (e.g.
pneumomed1nstmum, rupture of spleen 01· slomnch nnd vasopressors, hypernlimcntation fluids, contrast
injury to the norta.
medications); (iii) to monitor central venous pressure; and
(iv) ncccss for hcmodialysis, plnsmapheresis or continuous
Nasogastrlc TUbe Insertion
rcnnl replacement therapies.
fodicatious: Nnsogastric intubation is usunlly performed
for: (i) ndministrntion of mcdicntions or nutrients in uncon· Procedure: Principles common to all central venous cathe-
scious or nnorexic children; (ii) gns trointestinnl decompres· ter procedures, regardless of site, include: (i) strict attention
sion in case of intestinal obstruction or traumn; nnd (iii) to asepsis; (ii) use of the Seldinger technique (placement
gastric lavage in a patient with upper gnstrointestinnl over a guidewire minimizes trauma and hematoma forma-
bleeding or toxin ingestion. tion nnd enhances successful cannulation); (iii) adequate
sedation to minimize movements; (iv) attention to appro-
Contraitrdicatio11: (i) Suspected basilar skull frncture, priate location of catheter tip, avoiding high-risk sites such
(ii) maxillofacial trauma as ventricles and left atrium, verifying tip position with a
Proced11re: The largest size tube that does not cause undue radiograph; (v) avoiding placement in presence of a
discomfort to the child is chosen. Typically, an 8 Fr tube is bleeding diathesis; and (vi) continuous monitoring of vital
used in neonates, lO Fr for a 1-year-old and increasing s izes signs and oxygen saturation.
in childhood up to 14-16 Fr tubes in teenagers. The length
Sites: The site of access depends on the indication
of tubing to be passed is estimated by adding 8-10 cm to (Table 29.1).
the distance between the nostrils to the xiphoid process.
The child is prepared by explaining the procedure as fully i. External jugular vein. The external jugular vein can be
as possible; sedation is rarely needed. identified easily. There is less risk of pneumothorax.
Infants and obtunded children are placed supine with Complications are minimal because of the superficial
position of the vein and the ability to compress the
the head turned to one side. The curved tube is straightened
vein to prevent hemorrhage.
and its patency checked with a syringe. Application of a
lubricant facilitates atraumntic nasal passnge. The tube is ii. Internal jugular vein. Internal jugular vein cannulation
grasped 5-6 cm from the distal end and advnnced poste- provides an excellent approach to the central circula-
riorly along the floor of the nose. It is inserted with its tion with a high success rate and minimal compli-
natural curve pointing downwurd in order to go past the cations. Carotid artery puncture and pneumothorax
bend of the posterior pharynx easily. The procedure is are the most common complications. With left-sided
discontinued temporarily, if the child coughs or gngs or if cannulntion, there is potentinl for injury to the thoracic
the tube emerges from the mouth. When the tube is passed duct and there is a higher ris k for pneumothorax
successfully to the measured length, its position is checked. because the apex of the left lung is higher than on the
Using a 5 mL syringe filled with nir nttnched to the proximal right.
~-•,__,...,
; . .~'·
,.fF..,
_
•
_
•
• ••
.,,.,J..l t.,.
A • :',,,
_..o
• - Table
· -.-
29111:....,.Pre;erred
.. - .
choices
•
for placement ofI central
,.,. ,
line
"
Llnd~c~!ID{l ·-~
:.i.., •.J- "-' "'• o,
iii. S11bdavim1 vdn cm1111tlalim1. This vein is the preferred site c0 ,,,11 1;wtiot1s: The following complications may o.c~ur:
in patients with long-term cnthetcr rL•quin~mcnts been use (i) puncture of the calcancus, resulting in nccrohzmg
of its relatively hii;h level of palil'l1l comfort nnd cnsc of chondrilis or ostcomyclilis; (ii) calcified nodules. ?f t~e
cnthetcr mnintcnancc. ln pnli1.mts wilh hypovolcmia, thc heel; (iii) hcmolysis, resulting in falsely cle~ated bthrub~
subclavinn vein docs not collnpse as rcndily ns other amt potnssium levels from mechanical tra.uma,
major vessels. Major complications include pncumo- (iv) erroneously high glucose values due to alcohol m the
thorax, subclavian artery puncture, or occasionally, swnb; and (v) innccurate pC02 and p02 v(llues from poor
hemothorax. The chief long-term risk is subclavian vein blood flow.
stenosis.
iv. Fc~moml Vl.'ill ca111111lat io11. Femoral vein cannulntion is the Umblllcal Vessel Catheterlzatlon
most common site for central vein cannulation ns it is ltulicatious: The umbilical vein is a convenient route for
easily accessible. Main complications are the risk of vascular access in newborns during the first 7-10 days of
arterial puncture, infection, and rarely, deep vein throm- life. The route is used for administration of intravenous
bosis (more common with long-dwelling catheters in fluids or drugs during neonatal resusc~tation, ~hen
adolescents). establishing peripheral venous access 1s technically
difficult. It is also employed as a route for central venous
Capillary Blood (Heel Prick)
pressure monitoring and for performing exchange bl~od
Indications: Heel prick is a useful technique to obtain arte- transfusion. Cannulation of the umbilical artery provides
rialized capillary blood for blood gas analysis, bilirubin, a route for arterial pressure monitoring or arterial blood
glucose, hematocrit and other parameters in newborns. sampling and alternative access for exchange transfusion.
Teclmiq11e: Figure 29.3 indicates the appropriate areas to Co11trai11dicatio11s: Omphalitis is a contraindication; the
use for heel punctures for blood collection. Prewarming the procedure should also be avoided in presence of peritoni-
infant's heel (using a cotton wad soaked in sterile warm tis or necrotizing enterocolitis.
water at40°C or a hot towel) is important to obtain capillary
blood gas samples as it increases the flow of blood, allowing Equipment: These include a 5 or 8 Fr catheter or feeding
collection of blood specimen. Hot water should not be used tube, 10 mL syringe, tape or silk suture to tie the base of
since baby skin is thin and susceptible to thermal injury. the cord, normal saline for flushing, intravenous tubing
After ensuring asepsis, a sterile blood lancet or a needle is and three-way connectors, a set of sterile drapes, sterile
punctured at the side of the heel in the appropriate regions instruments (small iris forceps, needle holder and scalpel
as shown in Fig. 29.3. The central portion of the heel is blade) and antiseptic for skin preparation.
avoided as it might injure the underlying bone. Blood
sample is obtained by alternate squeezing and releasing of Procedure: The neonate is placed beneath a radiant
calf muscles. warmer. Anesthesia is not required; the limbs are res-
trained gently. The abdomen and umbilicus are deaned
with chlorhexidine gluconate or povidone-iodine and
sterile drapes placed, leaving the umbilical area exposed.
Arterial catheterlzatlon
1739 -
Imlicatlo11s: Arterial c«thcterlzntlon mny be llCl' d('d (I) to
monitor blood pressure continuously, ei;pcclnlly In lwmn·
dynamically unstable patients; flnci (II) to fr1!q11cntly
monitor arterial blood gas.
Sites a11d procedure: Radial flrtery cannulntlon IH fl prlnrnry
site of arterial cannulation In infonts and childrnn. Right
radial artery cannulation is performed when prl 1h1ctill1
~
infusion wil'hout significant subcutaneous infiltration. The
stylet is removed. Proper placement is confirmed by aspira-
tion of bone marrow into a 5 mL syringe and free flowing I
dcsi red intra venous tubing and solution. The site is observed I
I
Peritoneal Dialysis
After the site is chosen, xylocaine is injected with a small
needle to produce a skin wheal. The skin is then tilted This modality of dialytic support is used for renal replace-
anteriorly so that further infiltration into the subcutaneous ment therapy both in acute kidney injury (AKI) and end-
tissue is in a different plane (Z tracking). A needle or over- stage renal disease. Catheters placed surgically for chronic
the-needle catheter is then advanced using the Z tracking ambulatory peritoneal dialysis are not discussed here.
technique and at an angle perpendicular to the skin.
Indications: The modality is used in patients with AKI in
Continued aspiration of the needle is used until peritoneal
whom dialysis is indicated (Chapter 17) and hemodialysis and
fluid is aspirated. Approximately 10-15 mL of fluid is
continuous renal replacement therapies are not available,
aspirated for studies. Appropriate studies may include
orifhemodialysisiscontraindicated. Thetechniqueiswidely
cultures and Gram stain, cell count, cytology, amylase, LOH,
available, inexpensive and technically easy to perform even
bilirubin, albumin and protein. If the paracentesis is per-
in newborns.
formed for therapeutic purposes, a catheter should be placed.
C~ntr~i~dications: Relative contraindications to peritoneal
Complications: Complications include hemorrhage, fluid
dialysis include recent abdominal and/ or cardiothoracic
leak, intestinal or bladder perforation, and hypotension,
surgery, diaphragmatic peritoneal-pleural fistula, fecal or
if large volumes are removed.
fungal peritonitis and abdominal wall cellulitis.
Catheterlzatlon of Bladder Pr~cedu~e: Ac~e~s for peritoneal dialysis can be achieved
: -~~·
. -. . . . .
Fig. 29.9: Peritoneal dialysis: (a) Stiff uncuffed catheter used for acute peritoneal dialysis; (b) Soft single cuff Tenckhoff catheter
Inserted bedside for acute dialysis; (c) Usual site of catheter insertion is in midline below the umbilicus or two-thirds of
the distance between umbilicus and anterior superior iliac spine; (d) Device for automated control of dialysis and aseptic han-
dllng; and (e) Infant undergoing dialysis with soft Tenckhotf catheter
and guiding the tip of the catheter into the left iliac fossa. parameters. Acute manual PD requires constant super-
The trocar is removed and the catheter attached to a three- vision to ensure accurate inflow, dwell and drain times and
way connection to the peritoneal dialysis fluid and the drain the maintenance of a record of exchange and drain vol umes
bag. Once easy inflow and outflow are confirmed, the and net ultrafiltration. By comparison, the use of the
catheter is secured with a purse-string suture and manual automated cycler reduces need for constant supervision
cycles of dialysis are initiated. and record maintenance and decreases the number of
The soft single cuff catheter is inserted using an intro- manual interruptions and risk of peritonitis.
ducer kit using the modified Seldinger technique. A tunnel Complications: Abdominal pain or discomfort may occur
is created in the soft tissue so that the exit site is away from due to abdominal dis tension, improper position of the
the entry point into the peritoneum an~ the cu~f prote~ts catheter or peritonitis. Mild hemorrhage is frequent during
from bacterial migration. This catheter ts associated with catheter placement, particularly with rigid acute catheters.
lower risk of peritonitis, particularly if used with an auto- Leakage around the PD catheter site is managed by reducing
mated cycler device (Fig. 29.9d). It can be capped when not the exchange volume or placing a suture at the exit site.
in use, allows ease of nursing, and can be used for several Inadequate drainage is due to improper placement of the
weeks (Fig. 29.9e). catheter tip or decreased bowel motility. Bowel perforations
is rare but may be observed with placement of stiff catheters.
Prescription: Acute PD can be performed intermittently or Metabolic complications include hyperglycemia, hypokale-
continuously depending upon the desired amount of fl~d mia, protein losses and hypernatremia.
and solute removal, and either manually by nurses or via
an automated d evice. About 20-30 mL/kg is infused over Bone Marrow Aspiration and Biopsy
5 min, kept in the abdomen for 20-40 min, and then drained Aspecial bone marrow needle is introduced into the bone
out. Ul trafiltration should not exceed 5-10% of bodYweight marrow space, and a sample aspirated for analysis. A mar-
over 24-48 hours. The prescription is modified every row biopsy is taken to ascertain the cellularity and
6-12 hours based on clinical evaluation and laboratory architecture of the marrow.
- 744
l~~fio?L;;;: Bc:c::- ~w asoll'atiim and hiopSY are spines (or fur the tibial site, the entire leg up to the distal
mm.:at:-d m cr~ciP=-;J...~
=- - - ~
bi.to\- ID-~. ~ec-
&
hiliofthidt)anddraped.Theposteriorsuperioriliacspine
pb.ine.j ttrrcn:.,_'-'-~; .. m a::...~""3s ma..."lier to role is Iocated~b"\- tracing the iliac crest baoovards to its most
out sioriiic::...~t [.>a:3.1! ,,.~ such as l\lllphoreticular
~ ~ -- - - prominent .ind ele\"ated point About 2 mL of 1% lidocaine
milig::n=:...;:y ·a~..r <-=-~=-- ::>stic err m~~o-o-en.ous Ieu..~ is injected subcutaneously into the periosteum. The bone
mi.a. Ho.:i~b rr ~.-Hoccb lnnurwma. chronic mn:- marroK nero.Ie is held firmly in the dominant hand with
lcid la~"',;,1:1,~c:i._-'6~~~=- m~~~);h:f"J?k.~.: the index finger placed m·er the needle to act as a guard.
err ap2=,,4:i~ amrm;"'; ::i::e;-.::....&rl-=-..~c ar.en'.ia; s:de:ro:,!a.stic The need.le is advanced. perpendicularly into the identified.
anemia; r~ ::n"\..-erl-.2T5 ~ ~~~ - fta:nrn--ha£R-..--tcEs
-r o _ area -....ith twi..qing motion till bone is felt. On advancing
~-ndrmnr.; 5n...~ ::rx~· ~~-;; (refutobLb-roma. n..."'ll.ro- further-, a 'give way' is felt that indicates that the needle is
bk.~"'13); ir..filtrafu-~ 5tc:r2.ge di.~'6 (Gaudter di..~c:e) in the bone marrow. The stylet is removed and a 20 ml
OT infections, lll\OJTing m~ l-on.e ffian"O\\- (kala-azar, syringe attached. The piston is pulled to create negative
tuberado-.3$)_ pres..'tL..--eanda..'Pirateslowl~-aroundO.SmLofmarrow.The
snin_ae is d.i..<::eorLnected and the marrow placed on slides.
Sitzs: The iliac cest is me ~-05! cummonh- u_-.ed. site. 1he
To ~k.e a touch preparation, the marrow is spread on the
sternum ?s net ;:-referred mcimd..i.cn b-ecau_~ of as:-.odated
slide by placing another glass slide so as to smear the mar-
pain and me ::ris.k of tjm tng u...1de..-tyi."'lg "\"ital structures.
row gent!y. Additional slides are prepared. similar to a peri-
~ta.rrow ::n.a...- :-e ~"""1)irate.:i from the ~rorimal tibia medial
phera.l smear, u...<IDg another glass slide at 30° angle to spread
to tt-.e tibial h•~>y L"l m.-=anrs: (<l:y~-<>ld). This site is
the marrow in a tongue-shaped projection on the slide.
preferred in i:nia..i~ ~!a! bio~-y fro::n me
iliac site in young
children is di£fu:u.lt as U1'..r iliac rn:st is small and carries risk To perform marrow biopsy, the stylet is replaced and the
of injuring pe.hic -P_;:;,rera.. needle withdrawn slightly. The needle is advanced
through another- site in the bone. Once the needle is lodged
F.quipmnrt: \ ·arious types of borte marrow biopsy needles in the oone, the stylet is removed and the needle advanced
are aYail.able (Figs 29.Ha and b ). The Jamshidi needle and in rotatory motion through the marrow space. The needle
its modifications are u_.;;;ed -,,idely because of their light is \\ithd.rawn and biopsy specimen placed in a vial con-
wein<h*- !:h::>rnbe\·ellederu:ithatallowseasYcorin~ofbone
y .u...,..=:il..A.&..lt' 0.J , taining formalin.. Once the needle is removed, local pressure
a tapering end th.at racilita!cs ream~ry of marrm,· specimen is applied to allow bleeding to stop. Drapes are removed,
and suitability for oom a..<>piration and biopsy. the skin is deaned and pressure bandage applied..
Proadure: The child st.ou!d be fasting for 3-! hours before Aspiration from the tibia is performed in a similar man-
the procedure_The child is positioned. prone with face ner. The preferred site is medial to the tibial tubercle, one
turned to a side and the pehis stabilized by folding a sheet inch below the joint line to avoid the growth plate. The bone
below it If tibia is to be <!!.--pirated, the leg is slightly flexed cortex is thinner and the marrow space is reached more
at the knee joint. Sedation ,,;fu intra\·enous midazolam and ~ckly than"ith the pehic site. Obtaining a biopsy is often
ketamine is administered during continuous monitoring of difficult as the marrow is more spongy.
Liver Biopsy
lndi~tions: Llv~~iopsyisusedtoevaluatehepatichisto
logy m order to:_(~) diagnoseparenchymal liver disease (e.g.
neonatal hepatitis, suspected metabolic liver disease); (ii)
Wlde.rstand the cause of persistently abnormal liver tests;
(iii) determine the etiology of focal or diffuse abnormalities
on imaging studies; (iv) assess the prognosis of known liver
~a...--e (e.g.. ex~epatic ~il!ary atresia, autoimmune hepa-
titis, chro:U~ nral he?ahtis); (v) determine response to
therapeutic mterYentions; (vi) develop a treatment plan
based on histol~~·; and (vi~) monitor effects of hepatotoxic
drugs. Analys~s of the biopsy specimen may include
evaluation of histology, metal content, enzymatic assays
a • b and cultures for viral, bacterial, or fungal pathogen.
Ag.. 29.10: Need'ies for bone marrow aspiration and b!opsy. CmrtraindicatimtS: Absolute contraindications include co-
(a) Jcmshd needes; (b) Vrn ~ needle agulopathy,assuggested by lowplateletconnt (<60.000/µL)
hnportPnt Medlolll r>moud1mut .,.......= - -_......,. . . . . . . --~
or prolonged prothrombin time (intcrnntlonnl normnllzL•d
ratio >1.5), and an inability to remnln st Ill (with nr wl th1111l
sedation). Relative contrnindicntlnnH lncl11d u 111w111ln,
peritonitis, marked ascites, high-grndc blllnry ohHl l'lt(:llon,
and a subphrenic or right pleurnl Infection or uff11Hlnn.
Proced11re: The biopsy may be performed pcrcuh11wn11Hly
at bedside with or without ultrnso11nd guldnncu. An
ultrasound-guided biopsy carries lower risk of compll·
cations and allows visualization of llw livN and nny tlll}~l'l r10' 2?. 1I : l)an 1l1111tr11"'11111 J '.J' Ill ft .ti ttVIf /.JI I 11 l't /t}f I# /j '/(~ 1-JI
lesions. Uncommonly, the biopsy is perfnrnwd 11 H ln~ the
transjugular route, laparoscopicnlly or by wed gt! rcst•cllon 11111 nrn rl{1•d J11 kl'I ·11rif1tl tilf1 • j11rit ,,, >o'I•' ti 11• I1111 d••fl ,f II 11; 11rm:r
during laparotomy. Transjugulnr venous blopRy IH rib, HO illl '" 11Void l11J11rl11y, ""' 111•1ir11•1,iw "'"' lm11dl1• fUI
preferred in patients with severe coagulopnlhy. nlnK nlollK tlw J11w1·1· h1mlt·1' 111 rlbr,, 'I lw 11w dl1· l; IWPt~·11
The child should be fasting for 4-6 hourH. An cn n•f11IIy n11111}1, 11 Ji11rl:tA111 fll I plm w In ,, d1·111h ,,, 'I! I 111 I 1,, 'rj'IV
intravenous line is secured and the child mnde to lie! Wily' Hlllltill f " ' " j Ii f1•11 ll p1111 1'11 pt,,,.,~ nf 11 w ll ·11•ft,t JA IJll t, f hi~
supine. The abdominal girth is mensured nt the umblllcuA lf'.
lip of tlw 111•1•dl1• ril11>11ld n·•il J111;I 1J;y1111d 1: <,,11Y-<ule :ind
to allow subsequent comparisons. The lower border of should 111ov1• w1·JI wltl1 w 11pln1t)1111, 1IW Yi"' ' 1~ fm:d 1111d tt11J
liver is localized by palpation or percuAsion, nnd itR 1wt~d le wit hd '"' w111jlll1kI y, '1'h1•fl,1mpl1d11 t r<o1~(1·m~l to vfah,
position on the midclavicular line mnrked . l!.B. form nli11 for I d1,f1111.1th11l11~y,
During continuous monitoring o f vitnl signs, sedntion Tlw l>lopuy 11lh• lt11>1 ..1J•·d wlth tin turi: lotf l~1'' ;;nd ~re?'
is administered. The site of biopsy is chosen based on the sure drc'1iHl11g appllt·d 111 pn-ve11t 1Jle•1tHfl// 1111 • rl111t1, '~
liver span. If the liver is palpable, a subcostal approach may monlton•d ovc!r till! 111~x l 6-S~ houm for t;j h1r;j rtJ1;,,
be used. However, a right lateral transthor'1cic approach is tochypnrn1, hypoh:1111l1111 ;1111J hH:nw.1: i1~ abdurr1J1,,,1 v~rth
most conunon, in which the needle is inserted in the tenth and cxccRfilve pain, which irwy w ;sit,t'•t 111f1:rrv1I bl1: 1·d111;y
intercostal space in the midaxillary line, nftcr confirming
liverdullness. Localanesthesiaisadministered.Thebiopsy Co11111llcnt/011r1: Compliratl111111 lnc Jud l• h1l rn·iibdi;u1inaJ
is usually performed using a sprin~-loadcd scmi'1ut~matic
hcmorrha81!, l>lllriry 1rn rif11nlti t>, lwpal l J1u:e r:J tl1 u l,
biopsy gun (Fig. 29.11) of size ~8 (infants~ or 16 (chtldrcn) hcmothorn x, Jwmobllia, pn eumothorau, ~a ll b l :srJch:r '''
gauge. The gun is loaded and its needle inserted through
lntcslinal perforation and iatmw:nk 11rtt:ri ovt't1<1U'> fi•.tul;1.
Chapter
30
Rational Drug Therapy
Anu Thukral • Kana Ram Jat
746
Rational Drug Therapy I 747 -
Cl~un> ofd11ct11::- artf'ria..~us i1111ronatr::: 10 mg/kg/dny PO Sirk <1)i•c:ts: Resplmtory distrc!:ls, increased intracrnnial
followed by 5 mg/kg/ day q 2-l hr for 2 dnys pressmc, sdiures
Si1fe effects: Nnusea, vomiting. ms.hes Cv11tmi11dimtio11: Respiratory failure, obstructive airway
discnsc
No.oroxen
juvenile idiopathic artlrritis: 10-20 mg/kg/dny PO q 12 hr ANTIARRHY!HM_!CS
Analgesia 5-7 mg/kg/dose PO q 8-12 hr (nftcr menls) Adenoslne
Side effects: Nausea, vomiting, rashes 0.1 mg/kg/dose (initial maximum dose 6 mg) rapid IV
(owr 1-3 sec); if no response in 1-2 min 0.2 mg/kg bolus
Diclofenoc Sodium To ensure thnt the drug reaches the circulation, administer
1-3 mg/kg/day PO q 8 hr directly into a vein with a three-way stop cock with 5-10
Side effects: Gastric bleeding, ulcer mL of saline flush ready to push immediately; maximum
single dose 0.25 mg/kg or 12 mg
Mefenamlc Acid Sidl' cfft•cts: Transient chest pain, dyspnea, flushing,
bronchosposm. Carbamazepine and dipyramidole
25 mg/kg/day PO q 6--8 hr
increase the toxicity I effect of adenosine.
Antipyretic dose: 5-8 mg/kg/ dose
Side effects: Gastric bleeding, rash, seizures Atropine Sulfate
lndomethocln O.Ql mg/kg/dose SC or IV
The dose can be repeated after 2 hr (max 4-6 times a day).
1-3 mg/kg/day PO q 12-24 hr
Orga11opl1ospl10r11s poisoning: 0.02-0.05 mg/kg every 10-20
Dose for ductal closure depends on the age of U1e neonate
min until atropine effect, then q 1-4 hr for at least 24 hours
(fable 30.1)
Side effects: Oliguria, hypoglycemia, platelet dysfunction Side <'f/l!cls: Dry mouth, blurred vision, tachycardia, urinary
retention, constipation, dizziness, hallucinations, restless-
ness
1 Table 30.1: lndomethacin dose (mg/kg) In neonates
Age at first dose 1st 2nd 3rd Lldocalne Hydrochloride
<48 hours 0.2 0.1 0.1 1 mg/kg/dose (maximum dose: 100 mg) slowly IV; repeat
in 10-15 min for two times; maximum total dose 3-5 mg/
2-7 days 0.2 0.2 0.2
kg within the first hr; endotracheal dose is two to three
>7 days 0.2 0.25 0.25 times the IV dose.
Continuous infusion 20-50 µg/kg/min IV /IO (do not
Tramadol exceed 20 pg/kg/min for patients with shock or CHF);
administer 1 mg/kg bolus when infusion is initiated (bolus
1-2 mg/kg q 4-6 hr up to maximum of 400 mg/ day; avoid
not given within previous 15 min)
below 14 yr of age
Side effects: Hypo tension, seizures, asystole, respiratory arrest
Side effect: Seizures, renal and hepatic dysfunction
Phenyto/n Sodium
I
Narcotic Analgesics (Oplolds)
Arrlzytlm1ia: Loading 1.25 mg/kg IV over 3 min and repeat
Fentony/ every 5-10 min to a maximum total dose of 15 mg/kg or
0.5-5 µg/kg/dose q 1-4 hr IV; may be administered as a until arrhythmia reverts or hypotension develops;
continuous infusion 1-5 µg/kg/hr maintenance 5-10 mg/kg/day PO q 12 hr
Potent narcotic analgesic; 0.1 mg dose possesses analgesic Status epileptirns: Loading 15-20 mg/kg IV, do not exceed
activity; equivalent to 10 mg of morphine. 1-3 mg/kg/min, maintain with 5-8 mg/kg/day PO or
Side effects: Rapid infusion may cause chest wall rigidity; IV q 12-24 hr
respiratory distress and respiratory arrest. Side effects: Gum hypertrophy, hirsutism, hypersensitivity,
megaloblastic anemia, osteomalacia, vestibulocerebellar
Morphine syndrome
0.1-0.2 mg/kg/dose q 4 hr (maximum 15 mg) IV /IM/SC
Continuous infusion in neonates 0.01-0.02 mg/kg/hr, Procolnamlde
infants and children 0.01-0.04 mg/kg/hr Arrhythmia: 3-6 mg/kg/ dose over 5 mins, repeat q 5 min
Naloxone (0.01 mg/kg IV) is an antidote in case of up to total of 15 mg/kg; IV infusion: 0.5 mg/kg/hr; oral
respiratory depression. 50 mg/kg/day PO q 3-4 hr
-748 Essential Pediatrics
ANTIFUNGAL AGENTS
•
Amphoterlcln B
discomfort.
Test dose 0.1 mg/kg IV; then start 0.25 mg/kg/day;
Qu/nolones (Table 30. 7) increase by 0.25 mg/kg daily, until dose of 1 mg/kg/ day;
Side effects: GI upset, renal failure, insomnia, dizziness and Dilute in 5% dextrose, saline; Protect from light
seizures; no concerns of arthropathy. Inhibition of liver Total dose should not exceed 30-35 mg/kg over
enzymes can result in elevated levels of theophylline. 4-6 weeks
Other side effects include: Rash, photosensitivity, raised Side effects: Febrile reactions, nephrotoxicity, hypokalemia,
transaminases, neutropenia blood dyscrasias
750 Essential Pediatrics
•
2.5-5 mg/kg/day
1 mg colistin base
= 30,000 IU
1 mg colistimethate
sodium = 12500 IU
lmipenem 0-4 wk old and <1.2 kg : 50 IV 12 hr Pruritus, urticaria, seizures, dizziness, hypotension,
.::
<1 wk old and 2!1 .2 kg: 50 12 hr elevated liver enzymes
~1 wk old and <!1 .2 kg: 75 8 hr
Child (4 wk-3 mo): 6 hr
100 mg/kg/ day IV q 6 hr
Child (>3 mo): 60-100; 6 hr
Maximum 4 g/24 hr;
Cystic fibrosis: 90; 6 hr
. .• . Maximum 4 g/24 hr
(Contd...)
-752 I Essentlal Pediatrics
Faropenem 200 Increased to 300 PO 8-12 hr Diarrhea, abdominal pain, loose bowel movement,
nausea, and rash; safety in infants not established
Ertapenem 15-30 IV/IM 12 hr Not approved for children less than 3 months,
diarrhea, nausea, headache
Va neomycin 3o-45 in neonate (dosage IV 6-8 hr Ototoxicity and nephrotoxicity (exacerbated with
and frequency varies with concomitant aminoglycosides); adjust dose in renal
gestation age); 40-60 failure
Linezolid 10 mg/kg/dose IV 12 hr Dysgeusia, constipation, diarrhea, dizziness,
PO 8-12 hr headache, anemia, leukopenia, thrombocytopenia
Teicoplanin 10 mg/kg 12 hr for 3 doses; IV, IM 24 hr Long half life. Less nephrotoxic; less catheter-related
then 6-10 phlebitis
Tigecycline 1.2 mg/kg/dose IV 12 hr Hypersensitivity reactions, deranged liver function
(Max dose 50 mg) Use with caution In below 8 yrs
Nitrofurantoin 5-7 PO 6 hr Dizziness, hypersensitivity, icterus, interstitial
Prophylaxis: 1-2 pneumonitis, nausea, vomiting
Jsopr/nos/ne ANTIDOTES
Subacute sclerosing panencephalitis: 50-100 mg/kg/ day
POq 12hr Table 30.10.
Side effects: Use cautiously in renal dysfunction Ipecac syrup is used to induce vomiting.
Ratlonal Drug Therapy 755 -
•
external cephalic version): 250 µg IM
Side effects: Local site reactions (pain, discozn!o~t, or tender-
ness), fever, joint or muscle pain, headache,_dizziness, w_e~ Intravenous lmmunoglobulln (NIG)
ness, tiredness, itching, skin rash, nausea, diarrhea, vonuting Primary immunodeficiency: 400-500 mg/kg IV infusion
every 3-4 weekly
Anti-snake Venom Intravenous immunoglobulin (!VIG): 0.4 g/kg IV infusion
Mixhtre of four enzyme-refined, lyophilized, polyvale~t daily for 5 days; 1 g/kg/ day for 2 days or 2 g/kg in one
anti-snake venom (common Krait, cobra, Russell anti- day as IV infusion over 10-12 hr as single dose
snake venom) Side effects: Hypersensitivity reactions
5 vials (50 mL) for mild, 5-15 vials for moderate, 15-20
vials (150-200 mL) . 0
Tetanus Antitoxin
For severe features; smaller children may reqmre SO Yo
Prophylactic: 3,000-5,000 U SC, IM; Therapeutic: 10,000 U
more dose. .
,.Exclude horse serum allergy (0.02 m~ of ~:10_ dilut~d IM,IV
antivenin intradermally); then infuse antiverun diluted m Intrathecal: 250-500 U q 24 hr for 3 day
250 mL N/5 saline (20 mL/kg/hr) Side effects: Serum sickness, anaphylaxis
~ 758 I ~~~--~~--~--~---E_s~s~en~t~la~l~Pe~d=la~tr~lc~•:......----------------------~---
\-tlrlcella Zoster tmmunoglobulln Ftuttcasone Propionate
125 U/kg IM within 48-72 hr of exposure to vnricella MDI 25, 50, 125 µg/puff, rotacaps: 50, 100, 200 µg/puff:
Sidi" ~t(('Cts: Pnin at injt.'Ctlon side, hypersensitivity 100-1000 µg/day q 12 hr
Side cf/eels: Hoarseness, throat irritation, headache, dryness
BRONCHODILATORS, RESPIRATORY STIMULANTS AND in mouth/nose/throat, cough
ANTl·ASTHMA AGENTS lprotroplum Bromide
Adrenaline MDI 20 11g/p11ff: 2-4 puffs as needed
O.Ol mL/kg/dose (mnx 0.5 ml/dose) of 1:1000 solution Rotacap 40 11g/cap: 1-2 cap as needed
SC, rcpc.1t after 15-20 min Raspules 0.5 mg/2 ml, <1 yr: 125 µg/dose; >1 yr:
For resuscitation, 0.1-0.3 mL/kg/dose (1:10000) IV 250 pg/dose, repeat q 20 minutes for 1 hr (during
Side~ eJrc>cts: Tachycardia, palpitntions and anxiety
exacerbation); then q 6-8 hr
Side effects: Sinusitis, exacerbation of chronic obstructive
Amlnophylllne pulmonary disease
Status 11stlmratirns: 5-7 mg/kg IV loading, followed by Montelukast Sodium
infusion at 0.5-1 mg/kg/hr 1-5 yr: 4 mg PO once a day in evening; 6-14 yr: 5 mg once
Do not use loading dose, if already giving aminophylline. daily; >14 yr: 10 mg once daily
Ap11eic spells i11 preterms: 5 mg/kg IV loading, followed by Side effects: Fever, upper respiratory infection, headache,
1-2 mg/kg PO/IV q 8 hr pharyngitis, cough, abdominal pain, diarrhea, olitis
Sidt• effects: Tachycardia, tremors, irritability, convulsions media
Dobutamlne DIURETICS
Ml/Ir/none Hydroch/orthlazlde
50-75 µg/kg loading dose followed by 0.25-1.0 µg/kg/min. Neonate and infant <6 mo: 2-4 mg/kg/ day PO q 12 hr
Side effects: Extravasations may cause .tissue ~ecrosis, maximum dose 37.5 mg/24 hr
dizziness, headache, rarely severe allergic reactions ~mo and child: 2 mg/kg/day PO q 12hr; maximum dose
100 mg/24hr
Noreplnephr/ne Hypertension: Infant and child: Start at 0.5-1 mg/kg/day
0.05-0.1 µg/kg/min titrate dose to desired effect PO q 24 hr; maximum dose of 3 mg/kg/24 hr up to
(maximwn 2.0 µg/kg/min) 50 mg/24 hr
Side effects: Headache, bradycardia, hypertension Side effects: Almost similar to furosemide but less frequent
Meto/azone Dexamethasone
0.2-0.4 mg/kg/day PO q 24 hr 0.05-0.5 mg/kg/ day PO q ~ hr
Side effects: Hypotension, palpitations and hypovolemia, Congenital adrenal hyperplasia: 0.5-1.5 mg/ day
hypokalemia, hyponatremia Cerebral edema 0.5 mg/kg/dose IV /IM q 6 hr
Pulse dexamet1iasone:S mg/kg as slow infusion (maximum
Splrono/actone dose 100 mg)
Side effects:Weight gain, insorrmia, mood chang~, arne, dry
Neonates: 1-3 mg/kg/ day q 12-24 hr
skin bruising or discoloration, slow wound healing, nausea
Children: 1.5-3 mg/kg/day or 60mg/m2 /dayq12-24 hr; Croi;p: 0.3-0.6 mg/kg IM/ oral, single dose
not to exceed 100 mg/ day
Side effects: Dry mouth, dizziness, headache, irregular periods, Hydrocortlsone
gynecomastia, hirsutism, erectile dysfunction, hyperkalemia
Status astlzmaticus: 4-8 mg/kg/ dose IV q 4-6 hr IV
Trlamterene Endotoxic slzock: 50 mg/ m 2 initial dose followed by 50-150
mg/m2/day q 6 hr IV for 48-72 hr
2-4 mg/kg/ day q 12 hr
Acute adrenal insufficiency: 1-2 mg/kg/ dose IV, then
Side effects: Hyperkalemia, hyponatremia, dry mouth,
headache 25-150 mg/m2 /day IV or IM
Side effects: Hypertension, hyperglycemia, arrhythmias
Mann/to/
0.5-3 g/kg/ dose IV given over 30-60 min Prednlsolone
Side effects: Hypotension, tachycardia, fluid and electrolyte (Prednisolone, 5 mg = 0.75 mg betamethasone or dexa-
imbalance methasone, 4 mg methylprednisolone or triamcinolone,
20 mg hydrocortisone and 25 mg cortisone acetate)
HORMONES Acute ast11111a: 0.5-2 mg/kg/ day PO q 12-24 hr
Anti-inflammatory: 0.5-2 mg/kg/day PO q 8-12 hr
Betamethasone Neplzrotic syndrome: 2 mg/kg/day, q 12-24 hr daily; then
Anti-inflammatory: 0.0175-0.25 mg/kg/ day or 0.5-7.5 mg/ on alternate days
m 2 /day PO q 6--8 hr; 0.0175-0.25 mg/kg/day or 0.5-7.5 Congenital adrenal hyperplasia: 2 mg/kg/ day PO q 6-S hr
mg/m2/day IM q Cr12 hr or single dose in the morning
Fetal lung maturity (24-34 weeks); administer to mother Side effects (immediate): Moon fades, acne, increa_ d
12 mg IM in 2 doses 24 hr apart appetite, gastritis, hypertension, electrolyte disturbances,
Side effects (short tenn): Sodium retention-related weight glaucoma, pseudotumor cerebri
gain, glucose intolerance, hypokalemia, gastrointestinal Side effects (prolonged therapy): Myopathy, osteoporo::is,
upset and reversible depression of the hypothalamic- stunting, cataract, adrenal cortical suppression
pituitary-adrenal axis
Side effects (long term): Hypothalamic-pituitary-adrenal Methylprednlso/one
activity suppression, cushingoid appearance, hirsutism or 1-2 mg/kg/ dose IM or IV
virilism, impotence, cataracts and increased intraocular H_igh dose (pulse) t1zerapy: 15-30 mg/kg daily for 3-5 days
pressure, myopathy, osteoporosis Side effects:Hypertension, sweating, hyperglycemia, mood
changes, dyselectrolytemia, rarely arrhythmias
Cortisone Acetate
Physiological requirement: 0.7 mg/kg/day Triamcinolone
Therapeutic dose: 2.5-10 mg/kg/day q 8 hr 24 mg/ day PO q 8-12 hr; deep IM 40 mg or intra-articul,u
Side effects (immediate): Moon fades, acne, increased 2.5-15 mg; avoid <6 yr
appetite, reduced resistance to infections, headache, Side effects: Fluid retention, hypokalemic alkalosis, aseptic
gastritis, hypertension, electrolyte disturbances, glaucoma, necrosis of femoral heads, gastritis
pseudotumor cerebri
ACTH
Side effects (prolonged therapy): Myopathy, osteoporosis,
growth retardation, cataract, adrenal cortical atrophy For infantile spasms: 20-40 U /kg/ day IM q 24 hr for 6 week
or 150 U /m2I day q 12 hr for 2 weeks followed by a gradual
tapering, for dynamic testing (short ACTH stimulation test)
Fludrocort/sone <~months: 62.5 pg; 6 111011.t11s-2 years: 125 µg; >2 years 250 pg
Infants: 0.05-0.1 mg/ day PO q 24 hr; Children: 0.05---0.2 mg/ Side effe~ts : C/I hepa~1c ,da~age, nephropa thy, acute
dayPOq24hr psychosis, CHF, Cushing s disease, peptic ulcer, fungal
Side effects: Hypertension, hypokalemia, acne, rash infections, recent surgery
Vasopressln
L11gol's solution (125 mg/mL of total iodine) contains in each
Diabctesinsipid11s:5-20Uql 2 hIM·l 5_10 U/k I . 100 mL, 5 g of iodine and 10 g of potassium iodide. Fo;ir drops
IV infusion ' · m g mmute four times a day contain about 134 mg of iodine
Side effects: Hypertension, water intoxication hypo-
natremia ' Propylthlourocll
Neonate: 5-10 mg/kg/day q 8hr; <10 yr: 50-150 mg/day
Desmopressln q 8 hr; >10 yr: 150-300 mg/ day q 8 hr
Hemopltilia: I'.1fa11t~ >3 montlrs ofage and children: 0.3 µg/kg Maintenance: 50 mg q 12 hr
IV by slow mfus1on over 15-30 min beginning 30 min Side effects: Hepatitis, vertigo, rash, interstitial pneumonitis
before procedure; may repeat dose, if needed.
Erythropoletln
. Diabetes insipidus: Intransal 5_30 µg/day
Side effects: Water intoxication, hyponatremia Anemia ofprematurity: 25-100 U /kg/ dose SC or IV, 3 times
a week
Growth Hormone C11ronic kidney disease: 50-150 U/kg/dose SC or IV, 2-3
times a week
0.0~-0.2 unit /kg/ d ay SC or IM till accepted height is
achieved or bone fusion occurs SC route requires lower doses than IV; rotated through
arm, thigh and anterior abdominal wall.
T'.1rner syndrome: 0.11-0.14 unit/kg/day
Side effects: Local swelling, dizziness, nausea, pain at the
Side effects: Abnormal bone growth, abnormal touch site of the injection, fever
sensation, pseudotumor cerebri and hyperglycemia
Darbepoetln Alpha
lnsufln
Prolonged half life; administered less frequently; 0.45 µg/
Refer to Chapter 18 kg IV/SC once a week; 0.75 µg IV /SC once a fortnight
Side effects: Hypertension, seizures, venous thrombosis
Glucagon
Hypoglycemia (neonates/ infants): 0.025-0.3 mg/kg/dose q Octreotlde
30 min IM/IV /SC 1 µg/kg/hr (up to 50 µg/hr); given as continuous IV
Side effects: Nausea, vomiting, urticaria, respiratory infusion
distress Side effects: Local pain, stinging, tingling at site of injection,
hypothyroidism, conduction abnormalities, pancreatitis
Dlazoxlde
Hypertensive crisis: 1-3 mg/kg/dose up to maximum of Vitamin D
150 mg/dose Treatment doses of vitamin D for nutritional rickets (dose
Hyperinsulinemic hypoglycemia: 8-15 mg/kg/day PO q in IU).
8-12 hr
Age Daily dose for Single dose Maintenance
Hyponatremia, salt and water retention, gastrointestinal
90 days daily dose
disturbance, hyperuricemia
<3 mo 2000 NIA 400
Carblmazole 3-12 mo 2000 50,000 400
11 Potassium Chloride
1-2 mEq/kg/d PO q 8 hr; not to exceed 200 mEq/L in
central line infusions
Side effects: Hyperkalemia, GI disturbances, phlebitis
repeat in 15 minutes
Co11trai11dicatio11: Myasthenia gravis and acute narrow
angle glaucoma
F/umezanll
Reversal of benzodiazepine sedation (lV):
Sodium Bicarbonate Cllild: Initial dose: 0.01 mg/kg (max dose: 0.2 mg) given
1-2 mEq/kg/dose over 15 sec, if needed .after 45 sec, 0.01 mg/kg (maximum
dose: 0.2 mg) Q 1 mm to a maximum total cumulative
The dose is calculated as: dose of 0.05 mg/kg or l mg, whichever is lower. Usual
Base deficit x weight in kg x 0.6 =mEq, or ml of 7.5% solution total dose: 0.08-1 mg (average 0.65 mg); as an altern,ltive
of sodium bicarbonate for repeat bolus doses, a continuous infusion of o.oos-0.01
Side effects: Metabolic alkalosis, hypernatremia, hyp?- mg/kg/hr has been used.
kalemia, thrombophlebitis, intracranial hemorrhage m Side effects: Nausea, vomiting, dizziness, tremor, depression,
euphoria, agitation, palpitations, dyspnea, hyperventilation
neonates
--
Rational Drug Therapy 1763 -
Lorazepom M/dozotom
O. l mg/kg IV; repeat at 5 minutes; longer duration ofaction 0.07-0.2 mg/kg/ dose IM or IV . .
than diazepam; 0.03-0.05 mg/kg/ dose PO q 8-12 hr Pre-operative sedation or conscious sedation (mech~cal
Side effects: Confusion, depressed mood, hyperactivity, ventilation) above dose followed by 0.2-1 µg/kg/~ for
agitation, hostility neonates and 0.5-3.0 µg/kg/min for infants and children
Status epilepticus 0.2 mg/kg IV or IM followed by 0.1-0.2
C/onozepom mg/kg/hr
Intranasal 0.2 mg/kg may be used for acute seizure control
Infant and child <10 yr or <30 kg: initial: 0.01-0.03 mg/
Side effects: Respiratory depression, shock
kg/ day PO q 8 hr; increment: 0.25-0.5 mg/ day q 72 hr,
up to maximum maintenance dose of 0.1-0.2 mg/kg/ day Trlclofos
q Shr
20 mg/kg/dose for sedation PO q 12 hr
Child 2:10 yr or 2:30 kg and adult: initial: 1.5 mg/24 hr PO
q 8 hr; increment: 0.5-1mg/dayq72 hr; maximum dose: Side effects: Gastrointestinal disturbance, mild rash
20 mg/24 hr
Carbamozeplne
Side effects: Drowsiness, dizziness, muscle weakness, loss
of balance or coordination <6yr: 10-20 mg/kg/day PO q 8 hr, increment q 5-7 days
up to maximum of 35 mg/kg/24 hr; 6-12 yr: 10 mg/kg/
Chloral Hydrate 24 hr PO q 12 hr up to maximum 100 mg/ dose q 12 hr;
maintenance 20-30 mg/kg/ day q 6-12 hr
5-10 mg/kg/dose for sedation; 20-75 mg/kg/dose for Side effects: Dizziness, drowsiness, nausea, ataxi~, and
heavy sedation vomiting, pruritus, speech disturbance, xerostomia and
Side effects: Nausea and vomiting are more common, amblyopia
diarrhea; dizziness and drowsiness are less common
Clobazom
Chlorpromozlne
<30 kg: 5 mg PO q 24 hr, increase to 20 mg q 24 hr
2.5-6 mg/kg/day PO q 6 h >30 kg: 10 mg PO q 24 hr, increase to 40 mg q 24 hr
Chorea: Start with 50 mg/day PO; increase by 25 mg/day Side effects: Dizziness, drowsiness, anxiety, suicidal thoughts,
till controlled; maximum dose 300 mg/day withdrawal symptoms, lower doses in liver diseases
Neonatal tetanus: 1-2 mg/kg/dose q 2-4 hr
Side effects: Extrapyramidal reactions (e.g. Parkinson-like Pentobarbltol
symptoms, dystonia, tardive dyskinesia), drowsiness, Refractory status epilepticus: 10 mg/kg loading IV over
dizziness, skin reactions or rash, dry mouth, orthostatic 1 hr, maintenance 1-5 mg/kg/hr
hypotension, amenorrhea, galactorrhea, weight gain Side effects: Hypotension, respiratory s uppression,
arrhythmia
Fluoxetlne Hydrochloride
Phenobarbital
5-10 mg/day; maximum 20 mg/day
Side effects: Insomnia, weakness, anxiety, drowsiness, Anticonvulsant: 20 mg/kg loading IV; 3-5 mg/kg/ day IV
tremor, diarrhea, dyspepsia, nausea, nervousness, q 12-24 hr as maintenance
headache, xerostomia Side effects: Dizziness, respiratory depression, hypotension
•
Phenytoln Sodium
Ha/operldol
Arrhythmia: Loading 1.25 mg/kg IV over 3 min and repeat
Psychotic disorder: 0.05-0.15 mg/kg/day PO q 8-12 hr; every 5-10 min to a maximum total dose of 15 mg/kg or
agitation: 0.01-0.03 mg/kg/ day q 8-12 hr; chorea: until arrhythmia reverts or hypotension develops;
0.25 mg PO q 12 hr; 5-10 mg/day q 12 hr maintenance 5-10 mg/kg/day PO q 12 hr
Side effects: Extrapyramidal reactions, dyskinesia Status epileptirns: Loading 15-20 mg/kg IV, do not exceed
1-3 mg/kg/min. Maintain with 5-8 mg/kg/day PO or
Ketomlne IV q 12-24 hr
IV induction: 0.5-2 mg/kg at a rate not to exceed 0.5 mg/ Side effects: Gum hypertrophy, hirsutism, hypersensitivity,
kg/min; IM, oral, rectal: 3-10 mg/kg/dose; nasal and megaloblastic anemia, osteomalacia and vestibulo-
cerebellar syndrome
sublingual: 3-5 mg/kg/ dose
Minor procedures 0.5-1.0 mg/kg; sedative dose 2 mg/kg Fosphenytoln Sodium
The concomitant use of midazolam is beneficial 15-20 mg/kg/day; then 4-6 mg/kg/day
Side effects: Hypertension, hypertonia, dipl?pia, increased Side effects: Pruritus, dizziness, ataxia, nystagmus, contra-
intraocular pressure, salivary hypersecretion indicated in porphyria
-1s4 I Essential Pediatrics
I Ribavirln 6 g In 300 ml sterile water; nebulize q 12-18 hr/day for 3-7 d Seizures, congestive heart failure,
Oral: 10 mg/kg/day q 6-8 hr (max <10 yr: 150 mg/d; >10 yr; urinary retention, leukopenla
200 mg/d)
Senna Constipation: 10-20 mg/kg/dose, PO q 12-24 hr Loose stools, cramping
Sildenafil 0.3-3 mg/kg/day PO q 8 hr, 0.3-2 mg/kg/ dose PO q 6-12 hr Dizziness, light headed
IV bolus: 0.4 mg/ kg over 3 hr; followed by 1.6 mg/kg/d infusion
Sotalol Arrhythmia: 2-8 mg/kg/day, PO q 8-12 hr May cause arrhythmia
Succlnylcholine Neuromuscular blocking agent: 1-2 mg bolus, maintenance Hypot.ension, bronchospasm, hyper-
0.04-0.07 mg/kg/dose IV q 5-10 min as per desired effect kalem1a, malignant hyperthermla
Sulfasalazine Inflammatory bowel disease: Start at 40-75 mg/kg/day, Headache, nausea, rash, neutropenla
PO q 6 hr; maintenance: 30-50 mg/kg/day PO q 8 hr
Theophylllne Apnea In preterm: Loading 6-10 mg/kg; maintenance 2-4 mg/ ~I disturbance, tachycardia, feeding
kg/dose PO q 12 hr intolerance, irritability
Bronchodilator: 1~20 mg/kg/day
1-2 mg/kg IV over 10 min followed by 1-2 mg/kg/hr continuous Dizziness, faintness
Tolazoline
Infusion
---mo.s:: · ~ --
Rational Drug Therapy 1765 -
Side effects: ~epatotoxicity, irritability, hearing loss, Side effects: Postural hypotension, dizziness, foinlnmis,
nausea, vonuting, pyrexia nasal stuffiness, priapism
VJgobatrln
Tolazollne
Infantile spasm: 40-150 mg/kg/day PO q 12-24 hr 1-2 mg/kg IV over 10 min followed by 1-2 mg/kg/hour
Side effects: Visual field defects, GI and psychiatric symptoms in continuous infusion .
Side effect: Dizziness, faintness
VASODlLATORS
lsosorblde Dlnltrate Suggested Reading
0.1 mg/kg/ day PO q 6--8 hr • de Vries TPGM, Heming RH, Hogcrzcil HV, Frcslc DA. Gulde tu
Good Prescribing-A Practical l\lanunl. Essl'l\tlnl Drugs nnd
Side effects: Flushing, headache Medicines Policy, World He.11th Organiznlion, 1211 Gl•ncvn 27,
Nlfedlplne Switzerland 2000. Avail.lblc nt http:/ /www .who.int/mcdlchws/
areas/rational_use/en/https:/ /www . dru~s. com/
0.3 mg/kg/dose oral q 6 hr • Ritter JM, Lewis LO, ~·!ant TGK, Ferro A. A Textbook of Clinknl
Antihypertensive: 0.25---0.5 mg/kg/dose (maximumlO mg) Phannacology .md Therapeutics, 5th edn, 2008. London, Hoddl·r
POq6hr Arnold. Availt1ble at http:/ /pharmnresenrchllbrnry.com/wp·
content/uplo.1ds/2013/03/ A-Textbook·of-Clinicnl-Phnrmncology·
Vasodilator: 0.3 mg/kg/dose PO q 6 hr and-Therapeutics-5th-edition.pd r
Side effects: Hypotension, dizziness • Singh MB, 0..'0rari AK. Drug dosages in children, 8th cdn. New
Prozosln Delhi, Sagar Publications, 2009.
• Unni JC, Nair MKC, Menon PSN, Bansal CP. !AP l'cdlntric
Antihypertensive: 0.05--0.1 mg/kg/day q 8 hr (maximum Drug Formulary, 3rd edn. Mumbai: lndiJn Academy of l'cdintrics
0.5 mg/kg/ dose) 2012.
•
Chapter
31
Integrated Management of
Neonatal and Childhood Illness
Ajay Khera • Varun Alwadhi
Many well-known interventions like universal immuniza- treatment of sick children in an outpatient or primary care
tio~, es~ential newborn care, exclusive breastfeeding setting.
during first 6 months of life, appropriate complementary
feeding, oral rehydration therapy, and timely and Cllnlcal Guldellnes
appropriate use of antibiotics in pneumonia have proven The clinical guidelines target children less than 5-year-
to be effective in reducing child mortality. While each of old, the age group that bears the highest burden of
these interventions is successful, there is evidence to suggest morbidity and mortality. The guidelines represent an
that an integrated approach is needed to manage sick children . evidence-based syndromic approach to case management
Sick children often present with overlapping signs and that includes rational, effective and affordable use of
symptoms common to different illnesses and often suffer drugs. Careful and systematic assessment of common
from more than one illness, which may necessitate symptoms, using selected reliable clinical signs, helps to guide
different treatments. Another reason for integrated rational and effective actions.
approach is the need for incorporating preventive An evidence-based syndromic approach can be usr~d
strategies such as immunization and nutrition along with to determine: (i) Health problem(s) the child may have;
curative care. (ii) severity of the child's condition; and (iii) actions tbt
can be taken to care for the child (e.g. refer the child
INTEGRATED MANAGEMENT OF NEONATAL AND immediately, manage with available resources or manage
CHILDHOOD ILLNESS STRATEGY at home). In addition the guidelines suggest tl e
Integrated Management of Childhood Illness (IMCI) adjustments required to manage with the capacity of
strategy, developed by World Health Organization in health system and active involvement of family membr!s
in health care practices.
collaboration with UNICEF and many other agencies in
mid-1990s, combines improved management of common Principles of Integrated Care
childhood illnesses with prevention of diseases and
promotion of health by including counseling on feeding Depending oi: a c~ild's ~ge, various clinical signs a11d
and immunization. This strategy has been adapted and s~mptom.s differ m their degrees of reliability and
expanded in India to include neonatal care at home as diagnostic value and importance. IMNCI clinical
well as in the health facilities and renamed as Integrated guidelines focus on children up to 5 years of age. The
Management of Neonatal and Childhood Illness (IMNCI). treatment guidelines have been broadly described under
two age categories:
1. Young infants age up to 2 months
Essentlal Components
2. Children age 2 months up to 5 years
The IMNCI strategy includes both preventive and curative The IMNCI guidelines are based on the following
interventions that aim to improve practices in health principles:
facilities, the health system and at home. At the core of • All children under 5 years of age must be examined for
the strategy is integrated case management of the most conditions which indicate immediate referral
common neonatal and childhood problems with a focus • Children must. ~e routinely assesse d for major
on the most common causes of death in children <5 years symptoms, n.utr~tional, quality of interaction with a
of age. child, immuruzation status, feeding problems and other
The initial guidelines developed in 2003 were adapted problems
in 2009 and have recently been revised again in 2017 and • Only a limited number of carefully selected clinical
this chapter elaborates the clinical guidelines for the signs are used for assessment
766
Integrated Management of Neonatal and Childhood Illness
l1s1 -
• A combination of individual signs is used to classify Outpatient '1ealtT1 facility: Assessment; classification and
the severity of illness which calls for specific action identification of treatment; referral, treatment or counseling
rather than a 'diagnosis'. Classifications are color-coded of the child's caretaker (depending on classification(s)
and suggest referral (pink), initiation of treatment in identified); follow-up care
health facility (yellow) or management at home (green)
• IMNCI guidelines address most common, but not all
Referral liealtli facilihj: Emergency triage assessment and
pediatric problems treatment (ETAT); diagnosis, treatment and monitoring
of patient progress.
• IMNO management protocols use a limited number
of essential drugs Appropriate liome management: Teaching mothers or
• Caretakers are actively involved in the treatment of other caretakers how to give oral drugs and treat local
children infections at home; counseling mothers or other caretakers
• IMNO includes counseling of caretakers about home about food (feeding advice, feeding problems); develop-
care including feeding, fluids and when to return to ment support care (playing and communication) fluids;
health facility. when to return to the health facility; and the mother's own
The overall case management process is summarized health.
in Fig. 31.l.
Classification Tables
The case management of a sick child brought to a first-
level health facility includes a number of important IMNCI classification tables describe the steps of case
elements. management process: ASSESS, CLASSIFY and IDENTIFY
For all sick children age up to S years who are brought to a first-level health facility
!
ASSESS the child: Check for danger signs (or possible bacterial infection/jaundice). Ask
about main symptoms. If a main symptom is reported, assess further. Check nutrition and
immunization status. Check for other problems.
CLASSIFY the child's illness: Use color-coded triage system to classify main symptoms and his or '
her nutrition or feeding status
I
i
If urgent referral is needed and possible If no urgent referral is needed or
possible
+
Identify urgent Identify treatment
pre-referral treatment(s) needed needed for the child's classifications:
for the child's classifications Identify specific medical treatments
andfor advice
-
. i
IL
Follow-up care: Give follow-up care when the child returns to the clinic
_ If necessary, reassess the child for new problems
fig. 31 .1: Summary of the case management process
-768 j
TREATMENT. There are separate classification boxes for ·
d rawmg, fever / hypothermia, movement only when
main symptoms, nutritional status and anemia. stimulated or no movement at all.
IMNCI classifications are not necessarily specific This infant should be referred urgent!~ to the hospital
diagnoses, but they indicate what action needs to be taken. after being given the first dose of .1~tramuscular
All classifications are color-coded: pink calls for hospital ampicillin/ oral amoxycillin plus gentam1cm, treatment to
referral or admission, yellow for initiation of treatment, prevent hypoglycemia, and advi~e to the .mother on
and green means that the child can be sent home with keeping the young infant warm while arranging referral,
careful advice on when to return. and on the way to the hospital.
Classification tables are used starting with the pink A sick young infant with local ba~t~rial infection _is
rows. If the young infant or child does not have the severe the one with umbilicus red or drammg pus or skin
classifications, look at the yellow rows. For the classification pustules. This infant may be treated at home with oral
tables that have a green row, if the young infant or child antibiotics but should be seen in follow-up after two days.
does not have any of the signs in the pink or yellow rows, Additionally, if the sick young infant has jaundice,
select the dassifica tion in the green row. If the young infant classify for jaundice.
or child has signs from more than one row, the more severe There are two possible classifications
classifications is selected (Box 31.1). However, if the • A sick young infant with severe jaundice is one who
classification table has more than one arm (e.g. possible has yellow palms and soles or has jaundice at age
bacterial infection/jaundice, diarrhea in a sick child), one <24 hours or at age 14 days or more. This infant should
may have more than one classification from that box. be referred urgently to the hospital after being given
treatment to prevent hypoglycemia and advice to the
Box 31 .1: Effective communication with core provider mother on keeping the young infant warm while
It is critical to communicate effectively with the infant's mother arranging referral.
or caretaker. Proper communication helps to reassure the
• A sick young infant with jaundice is one who has
mother or caretaker that the infant will receive appropriate
care. In addition, the success of home treatment depends on jaundice but the palms and soles are not yellow. This
how well the mother or caretaker knows about giving the infant should be given home care, but mother should
treatment and understands its importance. be advised when to return immediately and should be
Parents, if correctly informed and counseled, can play an seen in follow-up in two days.
important role in improving the health status of their children
by following the advice given by a health care provider, by Assessing for Diarrhea
applying appropriate feeding practices and by bringing sick
Diarrhea is a main symptom, which is assessed if the
children to a health facility as soon as symptoms arise.
mother says it is present. Exclusively breast-fed infan ts
normally pass frequent soft stools. This should not be
OUTPATIENT MANAGEMENT OF YOUNG INFANTS AGE UP confused with diarrhea. A young infant is said to have
TO 2 MONTHS diarrhea if the stools have changed from usual pa ttern
Young infants have special characteristics that must be and the child is passing many watery stools (more water
considered when classifying their illnesses. They can than fecal matter).
become sick and die very quickly from serious bacterial
infections. They frequently have only general signs such Cllnlcal Assessment and Classlflcat/on
as few movements, fever or low body temperature. Mild All infan ts w1'th d'iarrhea should be assessed for presence
chest in drawing is normal in young infants because their of dehr:dration. A number of clinical signs are used to
chest wall is soft. The assessment procedure for this age dete~~me the le~el of dehydration: infant's general
group includes a number of important steps that must be condition (lethargic or. ~conscious or restless/irritable);
taken by the health care provider, which are given below. sunken eyes and elasticity of skin (skin pinch oes back
very slowly, slowly or immediately). g
Communicating with the Caretaker Allyounginfants 'thd' h
. wi iarr ea are classified for degree
It is critical to commtlllicate effectively with the infant's of. dehydration. .Young infants wi'th severe d eh yd ration .
mother or caretaker. Good communication techniques and will need IV flmds while . those wi'th d h d
some e y ration .
an integrated assessment are required to ensure that are. treated as plan.B with. oral rehydra ti on. y oungin. fanst
common problems or signs of disease or malnutrition are with no dehydration
. will require m fl
ore u1 to prevent
'd
not overlooked. d eh yd ration.
Checking for Possible Bacterial Infection/Jaundice Checking for Feeding Problems or Very Low Weight
A sick young infant with possible serious bacterial All sick young .infants seen in outpatient health facilities
infection is one with any of the following signs: not should be routinely evaluated for ad t f d' d
. . h k equa e ee mg an
feeding well, convulsions, fast breathing, severe chest in have their weight c ec ed). Infants w h o are very 1o....,
Integrated Management of Neonatal and Chlldhood Illness 1769 -
weight (weight <1800 g) are given pink classification and Non-urgent treatments, e.g. applying gentian violet
should be referred to a hospital. Infants who are low paint on skin pustules, should be deferred to avoid
weight (weight 1800-2500 g) need special attention to how delaying referral or confusing the caretaker.
they are fed and on keeping them warm. • If an infant does not need urgent referral, check to see
To assess the young infant for feeding problems the if the infant needs non-urgent referral for further
mother is asked specific questions about infant feeding to assessment. These referrals are not as urgent. Other
determine if the feeding practices are optimal. If there is necessary treatments may be done before referral.
no indication for referral the mother is observed for
breastfeeding. Breastfeeding is observed to see the signs Treatment In Outpatient Clinic and at Home
of attachment and whether the infant is suckling Young infants who have local infection, feeding problem
effectively. Mothers of infants with problem in feeding or low weight, or diarrhea with some dehydration should
are counseled appropriately. Infants who are not low have treatment initiated in clinic, which is continued at
weight for age and have no feeding problem are classified home. Counseling a mother I caretaker is critical for home
as 'no feeding problem' and counseled about home care care. The health professional should use good corrununica-
of young infant. tion skills while counseling the mother I caretaker for
treatment (Box 31.2).
Checking Immunization Status
Immunization status should be checked in all sick young Box 31.2: Effective communication and counsellng-APAC
infants. A young infant who is not sick enough to be • Ask and listen: Ask the mother I caretaker and listen carefully
referred to a hospital should be given the necessary to find out the young child's problems and what the motherI
immunizations before he is sent home. caretaker is already doing for the young infant
• Praise: Praise the mother/caretaker for what she has done
Assessing other Problems well
All sick young infants need to be assessed for other • Advise and teach: Advise the mother/caretaker how to take
potential problems mentioned by the mother or observed care of young child at home (for tasks which require mother/ '
during the examination. If a potentially serious problem caretaker to carry out treatment at home: give information,
is found or there are no means in the clinic to help the show an example, and let her practice) ,
infant, he should be referred to hospital. • Check: Before the mother/caretaker leaves, always check .
understanding by asking questions to find out what she
Identify Treatment and Treat '· understands and what needs further explanation
The next step is to identify treatment required for the
young infant according to the classification (see Charts). Advise when to Return
All the treatments required are listed in the 'Identify Immediately: Return immediately if the infant has any of
Treatment' column of the ASSESS and CLASSIFY THE these signs: breastfeeding or drinking poorly, becomes
SICK YOUNG INFANT. If a sick infant has more than sicker, develops a fever or feels cold to touch, fast
one classification, treatment required for all the breathing, difficult breathing, yellow palms and soles (if
classifications must be identified. The first step is to young infant has jaundice), diarrhea with blood in stool.
determine if there is need to refer the child to hospital.
All infants and children with a severe classification For follow-up visit: Return not later than 2 days if the
(pink) are referred to a hospital as soon as assessment is infant has: Local bacterial infection or, jaundice or diarrhea
completed and necessary pre-referral treatment is or feeding problem or thrush; and not later than 14 days
administered. Successful referral of severely ill infants to if low weight.
the hospital depends on effective counseling of the Next well cliild visit: For immunization and feeding
caretaker. counseling.
The first step is to give urgent prereferral treatment
(written in bold font in identify treatment section of chart). Counsel the Mother about her Own Health
This maybe:
During a sick infant visit, listen for any problems that the
• Administering first dose of antibiotic mother herself may be having. She may need treatment
• Treatment of severe dehydration or referral for her own health problems. If the mother is
• Prevention of hypoglycemia with breast milk; if young sick, provide care for her, or refer her for help. Advise her
infant is not able to swallow give expressed breast to eat well to keep up her own strength and health. Check
milk/ appropriate animal milk with added sugar by her immunization status and give tetanus toxoid if needed.
nasogastric tube Give the mother iron folic acid tablets if she is not taken
• In young infants with diarrhea, givin? frequent sips of them. Make sure she has access to family planning and
ORS solution on the way to the hospital. counseling on STD and AIDS prevention.
-no I ~------------~~~----....!:E=aa=e~n~tl~a~l~P~ed~l!at~rl~c!s__.~------------------------~-----~
OUTPATIENT MANAGEMENT OF SICK CHILD AGE Classificatio11 of cougli or difficult breath~ng: Those
2 MONTHS TO 5 YEARS requiring referral for possible severe pnew:noma or severe
disease. This group includes children. with any general
The assessment procedure is similar to that of young infant danger sign, or stridor when calm. Children Wl~ sev~re
including: (i) History taking and communicating with the pneumonia or severe disease most likely have an mva~ive
caretaker about the child's problem; (ii) checking for bacterial organisms and diseases that may be h.fe-
general danger signs; (iii) checking main symptoms; threatening. The patient needs urgent referral to~ hospital
(iv) checking for malnutrition; (v) checking for anemia; for treatment, such as oxygen, a bronchodilator. or
(vi) assessing the child's feeding; (vii) checking immuniza- injectable antibiotics. Pulse oximeter is u~ed to ~etemune
tion status; and (viii) assessing other problems. oxygen saturation and patient referred 1£ <90 Yo.
Communicating-History Taking Those who require antibiotics as outpatients be~ause
they are highly likely to have bacteri~l pneumonia. A
A sick child brought to an outpatient facility may have
child with cough or difficult br~athmg_ ~ho has f~st
signs that clearly indicate a specific problem. However, breathing and or chest indrawing is classified as having
some children may present with serious, nonspecific signs pneumonia. This child should not hav e_a g~neral danger
called General Danger Signs that do not point to a 0
signs, or stridor and his oxygen saturation is >90 Yo.
particular diagnosis. For example, a child who is lethargic
or unconscious may have meningitis, severe pneumonia, Those who simply have a cough or cold ai:'d do not
cerebral malaria or any other severe disease. Great care require antibiotics. Such children may require a safe
should be taken to ensure that these general danger signs remedy to a relieve cough. A child with cough a:'d c~ld
are not overlooked because they suggest that a child is normally improves in 1-2 weeks. However, a child with
severely ill and needs urgent attention. chronic cough (more than 14 days) needs to be further
assessed (and, if needed, referred) to exclude tuberculosis,
Assessing for General Danger Signs asthma, whooping cough or another problem.
The following signs should be routinely checked in all
children: (i) History of convulsions during the present Diarrhea
illness, (ii) unconsciousness or lethargy, inability to drink A child with diarrhea passes stools with more water than
or breastfeed when mother tries to breastfeed, or to give normal. A child with diarrhea may have (i) acute watery
child something to drink; (iii) child vomits everything; and diarrhea (including cholera); (ii) dysentery (bloody
(iv) child is presently having convulsions. diarrhea); or (iii) persistent diarrhea (diarrhea that lasts
If a child has one or more of these signs, he must be 14 days or more).
considered seriously ill and will almost always need Clinical assessment and classification. All children wifo
referral. diarrhea should be assessed for dehydration based on the
following clinical signs: General condition (lethargic er
Assessing for Main Symptoms unco~scious or restless/irritable); sunken eyes; child 's
After checking for general danger signs, the health care reaction when offered to drink (not able to drink or
provider must enquire about the following main drinking poorly or drinking eagerly /thirsty or drinkin.-
symptoms: (i) Cough or difficult breathing; (ii) diarrhea; normally) and elasticity of skin (skin pinch goes back ve;,.
(ill} fever; and (iv) ear problems. If the symptom is present slowly, slowly or immediately). In addition a child with
the child is evaluated for that symptom. d~arrhea sho':1ld be asked how long the child has had
diarrhea and if there is blood in the stool Thi ill 11
'd ·f· · · SW a OW
Cough or Difficult Breathing i enh 1cahon of children with persistent diarrhea and
dysentery.
Four key clinical signs are used to assess a sick child with
cough or difficult breathing: Fever
• Fast breathing: Cut-off respiratory rate for fast breathing
is ~50 breaths per minute for a child 2-12 months and All .cases with fever are suspected to h ave ma1aria. after
~40 breaths per minute for 12 months up to 5 years
rulmg out other common causes d h Id b
. . t df nfir an s ou e
• Lower chest wall indrawing mvesti.~ ; . or~ ki m(~tion of malaria by microscopy
or. rap1 iagnos c. t DK) so as to ensure treatment
• Stridor with. full therapeutic dose with appro riate dru all
• Wheeze confirmed cases. P g to
Patients with wheezing and either fast breathing or History of duration of fever is important . .
1
chest indrawing are given a trial of rapid acting inhaled fever. If fever has persisted daily for mar th m eva u~g
bronchodilator for up to three times 15-20 minutes apart. the child needs to be referred to hosp'tel fan seven ayst
. · Th 1 a or assessmen
The patient is observed again for respiratory rate and signs ~d d1agn~stic tests. e other signs looked for in a child
of chest indrawing, and reclassified as follows: . )
with fever include general danger si"gns (assesse d ear11er
Integrated Management of Neonatal and Childhood Illness
1771 -
and signs of meningitis, e.g. stiff neck. Besides these, signs Checking for Anemia
of measles such as cough/ difficult breathing, diarrhea, Palmar pallor can help to identify sick children with severe
cornea clouding, mouth ulcers and ear infections. Before
anemia. Wherever feasible, diagnosis of anemia can be
classifying fever, one should check for other obvious
causes of fever. supported by using a simple laboratory test for
hemoglobin estimation. For clinical assessment of anemia
Ear Problems the color of the child's palm is compared with examiner's
own palm. If the skin of the child's palm is pale, the child
A child with an ear problem may have otitis. It may be
has some palmar pallor. If the skin of the palm is very
acute or chronic infection. If the infection is not treated,
pale or so pale that it looks white, the child has severe
the ear drum may perforate. The mother is asked about
palmar pallor. Pallor is classified as severe anemia, anemia
history of ear pain and ear discharge or pus. The child is
or no anemia.
examined for tender swelling behind the ear. Based on
these clinical findings a child can be classified as
mastoiditis, acute ear infection, chronic ear infection or Assessing Child's Feeding and
no ear infection. Children with mastoiditis are classified Development Support Care
as severe illness and referred urgently to hospital. Children All children less than 2 years old and all children classified
with acute ear infection are given oral antibiotics and those as moderate acute malnutrition need to be assessed for
with chronic ear infection are advised to keep the ear dry feeding and development support care.
by wicking. Feeding assessment includes questioning the mother
Checking for Malnutrltlon or caretaker about: (i) Breastfeeding frequency and night
feeds; (ii) types of complimentary foods or fluids,
After assessing for general danger signs and the four main frequency of feeding and whether feeding is active; and
symptoms, all children should be assessed for malnutrition. (iii) feeding patterns during the current illness. The mother
There are two main reasons for routine assessment of or caretaker should be given appropriate advice to help
nutritional status in sick children: (i) To identify children overcome any feeding problems found.
with severe malnutrition who are at increased risk of
mortality and need urgent referral to provide active Assessment of development support care includes
treatment; and (ii) to identify children with suboptimal assessment of mother's sensitivity and responsiveness
nutritional status resulting from ongoing deficits in dietary to the child's needs through questioning the mother or
intake plus repeated episodes of infection and who may caretaker about: (i) Playing with the baby; (ii) talking to
benefit from nutritional counseling. the baby, and (iii) making the baby smile and the learning
pattern of the child. The mother or caretaker should be
Clinical assessment and classification: Edema of both feet; given appropriate advice to help overcome any playing
weight for height; mid-upper arm circumference (only for and communication problems found (for more details,
children 6-59 months) refer to the section on counselling the mother or
The child is classified as Complicated Severe Acute caretaker).
Malnutrition when they have severe acute malnutrition
(edema of both feet, weight for height/length less than Identify Feeding Problems
-3 SD scores, or mid-upper arm circumference less than
It is important to complete the assessment of feeding by
115 mm) and at least one medical complication, including
any general danger sign, any severe classification, or referring to age appropriate feeding recommendations
pneumonia with chest indrawing or a feeding problem and identify all the feeding problems before giving advice.
in children under 6 months. Children classified as having Other common feeding problems are: Difficulty breast-
complicated severe acute malnutrition are at high risk of feeding, use of feeding bottle, lack of active feeding and
death from pneumonia, diarrhea, measles, and other not feeding well during illness.
severe diseases. These children need urgent referral to
hospital where their treatment can be carefully monitored. Identify Developmentally Supportive
{Family Interaction) Problems
If the child has at least one sign of severe acute mal-
nutrition, but does not have other signs of complication, It is important to complete the assessment of family
they are classified as Uncomplicated Severe Acute interaction and identify all the problems before giving
Malnutrition. A child is classified as Moderate Acute advice. Based on the mother's answers to the questions,
Malnutrition if the weight-for-age is between -3 and -2 identify any differences between the family's actual
Z-scores or MUAC is between 115 and 125 mm. The child interaction (sensitivity and responsiveness) and the
is classified as No Acute Malnutrition if the child has a recommendations. These differences are problems.
weight-for-age over -2 Z-scores, and has no other signs Some examples of interaction problems are listed in
of malnutrition. Box 31.3.
Box 31 .3: Examples of Interaction problems necessary pre-referral treatment is administered. If a child
only has severe dehyd_rat~on a~d n? other sev.ere
fomily interaction Recommmdt•d action
classification, nnd IV infusion 1s available m the outpatient
Mother reports, "she does Discuss ways to help baby see, clinic, an attempt should be made t~ rehy~rate th~ ~ick
not play with baby" hear, feel and move, appropriate child. The principles of r~ferral of a .sick child are s1m1lar
for age, ask caregiver to do play •
to those described for a sick young mfant.
or communication activity,
appropriate for age
Referral of Chlldren Age 2 Months to 5 Years
Mother reports, "she does If baby is less than 6 months ask
not talk to child or talks caregiver to looks into baby's eyes For all cl1ildre11 before referral
harshly to child" and talk to baby. For older 1. Prevent low blood sugar by giving breast milk or sugar
children give caregiver and child 1 water.
an activity to do together. Help 2. For convulsions give diazepam (10 mg/2 mL solution)
mother interpret what child is in dose 0.2 mg per kg (0.05 ml/kg) IV or rectally; if
doing and thinking and see child ' convulsions continue after 10 minutes, give a second
respond and smile. If the mother dose of diazepam.
scolds child, help caregiver
distract child from unwanted 3. For severe pneumonia or severe disease (as also for
actions by giving alternative toy or mastoiditis), give first dose of IV or intramuscular
activity. If the mother is not able antibiotic. Options for an intramuscular antibiotic for
to comfort child and child does not pre-referral use include (ampicillin plus gentamicin
look at the mother for comfort: combination, OR ceftriaxone).
help mother look into child's eyes 4. For very severe febrile d isease, give one dose of
and gently talk to child and hold 1 paracetamol for high fever (38.5°C or above); give first
child. dose of intramuscular quinine/ artesunate for severe
Mother tries to force smile Ask mother to make large gestures 1 malaria in high Plasmodium falciparum area, and give
or is not responsive to baby and cooing sotmds; copy baby's first dose of an appropriate antibiotic.
sounds and gestures and see
5. For severe complicated measles, give first dose of
baby's responses. 1
appropriate antibiotic, give vitamin A, and if there is
Mother says the child is Encourage more activity with the ;
clouding of the cornea or pus draining from the eye,
slow to learn child, check hearing and seeing.1
Refer child with difficulties I apply tetracycline eye ointment.
I 6. For severe dehydration, IV fluids should be given in
·-------·~ -- - the outpatient clinic according to WHO Treatment
Plan C. Give 100 mL/kg IV fluids. Ringer's lactate
Checking Immunization, Vitamin A and Follc Acid solution is the preferred commercially available
Supplementation and Deworming Status solution.
The immunization status of every sick child brought to a 7. For severe persistent diarrhea, treat dehydration before
health facility should be checked. After checking referral using WHO Treatment Plan B for some
immunization status, determine if the child needs vitamin dehydration and Plan C for severe dehydration.
A supplementation and/or prophylactic iron folic acid 8. For severe acute malnutrition, give first dose of
supplementation or deworming administration. intramuscular antibiotics. Options for an intramuscular
antibio~i~ for pr~-re~erral u se include ampicillin plus
Assessing other Problems gentarrucm combination OR ceftriaxone. Oral amoxicillin
The IMNCI clinical guidelines focus on five main can be an option.
symptoms In addition, the assessment steps within each
main symptom take into account several other common Treatment In Outpatient Clinics and at Home
problems. For example, conditions such as meningitis, Identify the treatment associated with each nonreferral
sepsis, tuberculosis, conjunctivitis, and different causes classification (yellow and green) in the IMNCI chart.
of fever such as ear infection and sore throat are routinely Treatment uses a minimum of affordable essential drugs
assessed within the IMNCI case management process. (Box 31.4).
knows how to give treatment, understands its importance • Reduction of signs of possible severe vacterial infection
and knows when to return to n health care provider. (PSBI) in young infants
Table 31.l lists the specific times to advise a mother or • Revised drug dosages for pre-referral treatment of
caretaker to retum to a health facility. possible severe bacte.rial infec.tion .
• Simplified classifications of diarrhea m young Infants
r~--·.·~- Tab~e 3~1: Follow-::up-vlslts ., ·=i • Mandatory assessment of breastfeeding in all young
When to return infants
Immediately • Revised immunization schedule and addition of
• Any sick child not able to drink or breastfeed, or becomes deworming as per immunization and deworming
sicker or develops a fever policy of India . .
• If child has no pneumonia: Cough or cold, also return if fast • Removed weight for age as cntena for referral and
breathing or difficult breathing referral of low birth weight aligned with other existing
• If child has diarrhea, also return if blood in stool or drinking new-born training packages
poorly • Added classifying danger signs as severe disease with
For follow-up visit (not later than ... ) addition of convulsing now
• 2 days: Pneumonia, dysentery, malaria/suspected malaria/ • Added use of rapid acting bronchodilator before
fever; malaria unlikely if fever persists; measles with eye or classifying wheeze with fast breathing/ chest indrawing
mouth complications. in children presenting with cough or difficult breathing
• 5 days: Diarrhea, if not improving, persistent diarrhea, acute • Revised signs for classifying pneumonia as per WHO
ear infection, chronic ear infection, uncomplicated acute recommendations
malnutrition/feeding problem, any other illness, if not • Added use of pulse oximetry for classifying pneumonia
improving.
• Revised classification of fever as per National Anti-
• 14 days: Anemia
Malaria Program guidelines including use of ROT and
• 30 days: Moderate acute malnutrition
drugs for treating malaria
Advise when to return for the next Immunization according to
• Signs for severe acute malnutrition revised
immunization schedule.
• Added early child development in the section o!:l
Salient Adaptations In IMNCI (2017) feeding counseling
In general the adaptations were undertaken to update as Suggested Reading
per global advancements and in line with the various • IMCI: Global Survey report. World Health Organization; 2()17
guidelines of India released from time to time. The Integrated Management of Childhood Illness Chart Book' :t.
adaptation took into consideration revised WHO IMCI Geneva: World Health Organization; 2014
charts released in 2014 and antimicrobial therapy • Oxygen therapy for children: a manual for health workers. G~ · n:
advancements. A major adaptation included incorporation World Health Organization; 2016
• Pediatric emergency triage, assessment and treatment: ca of
of Early Child Development messages along with critic~lly ill children: Upda ted guideline. Integrated Maruge:r,•:\!
nutritional counseling. of Child Illness. World Health Organization; 2016
• Not able to feed or J> Give first dose of ampici/lin /oral amoxycillin and
Classify • Convulsions or intramuscular gentamicin.
C>
ALL • Fast breathing (60 breaths per minute or POSSIBLE .•
ASK: LOOK, LJSTEN, FEEL: li> Treat to prevent low blood sugar.
YOUNG more) or SERIOUS
INFANTS • Severe chest indrawing or BACTERIAL
• Is the infant • Count the i> Warm the young infant by slcin to skin contact
having breaths in one • Axillary temperature 37SC or above (or INFECTION
while arranging referral
r~
diflirutty in feels hot lo touch) or
feeding? • Axillary temperature less than 35SC (or
mi"'•
Repeat the court INFANT
feels cold to touch) or
li> Advise mother how to keep the young infant
•Has the if elevated. MUST warm on the way to the hospital
infant • Look for severe chest indrawing. BE • Movement only when stimulated or no
had CALM movement al all.
;;. Refer URGENTLY to hospital
convulsions?• Look at the umbilicus.
-
Is it red or draining pus?
.___ • Umbilicus red or draining pus or LOCAL ;;. Give oral amoxycillin for 5 days.
• Look for skin pustules
BACTERIAL :;.Teach mother to treat local infections at home. 0
• Skin pustules.
• Measure aicillary temperature
(if not possible, feel for fever or low body
INFECTION )>Follow up in 2 days. z
Cll
temperature). 0
• Look at the young infant's movements :J
If infant is sleeping, ask the mother lo awake '---
m
him/her_ •Palms and soles yellow or li> Treat to prevent low blood sugar. i
- Does the infant move on his/her own? •Any jaundice at age < 24 hours or age SEVERE m
If the young infant is not moving.gently 14 days or more >Warm the young infant by skin to slcin contact :J
I~
And if the infant JAUNDICE Q.
stimulate him/her. while arranging rvfwral.
- Does the infant not move at all? has jaundice 0
• Look for jaundice?
Are the palms and soles yellow?
I/ >AcMse mother how to keep the young inhnt
warm on the way to the hospital
• Palms and soles not yellow JAUNDICE );>Advise mother lo give home care for the )'OlJll9 5"
infant Cll
Cit
Cit
Hollow up in 2 days.
I
AGE UP TO 2 MONTHS
I
Ttfr:IEN ASK::
Qoes tile young infant have diarrhoea?*
.
IF YES LOOK AND FEEL: . Two of the following l" Give first dose of intramuscular amp lc//lln (Oral Amoxyclllin)and
signs: gentamicin.
• Look at the young infant's general conditiCJl: II ·
SEVERE
Infant's movements 11 • Movement only when DEHYDRATION Hf infant also has another severe classification:
• Does the infant move on his/her own?
I
- Refer URGENTLY to hospital with mother giving frequent sips o
stimulated or no
ORS on the way.
• Does the infant move only when stimulated but movement at all -Advise mother to continue breastfeeding.
• Sunken eyes
~
then stops? -Advise m other how to keep the young In fant warm on the way
i
• Does the infant not move at all? Classify • Skin pinch goes back to the hospital
DIARRHOEA very slowly.
• Is the infant restless and irritable?