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About this Book

This book is served as an overview to General Paediatrics and specially tailored to UM`s teachings.
It integrates comprehensive information from various reliable sources (either lecturers` teachings,
seminar slides, standard textbooks or protocols). However, it would not be able to replace all
textbooks and students should still opt to refer standard textbooks for detailed understandings
and concepts. To those who have prior knowledge in Paediatrics, it will serve as a QuickReview for
revision purpose before final exam. Our team had tried our best to maintain the accuracy and
latest information within our capability. If there is any mistake or suggestion, please email us at
umpaedsfeedback@gmail.com.

Acknowledgement
We would like to acknowledge UPM for their old yet useful senior notes as our major inspiration
and references. Besides, this book follows essential concept and management listed in Paediatrics
Protocol as well. The compilation of this book is not possible without all references enlisted below
and we would express our gratitude and sincerely give a token of appreciation to each of them:
- Nelson Textbook of Pediatrics 20th Edition - WHO Pocketbook of Hospital Care for Children
- Nelson Essentials of Pediatrics 7th Edition - Netter`s Paediatrics
- Illustrated Textbook of Paediatrics 4th Edition - Netter`s Illustrated Human Pathology Updated Ed
- Easy Paediatrics - Handbook of Hospital Paediatrics 2005
- Examination Paediatrics 4th Edition - UM Paediatrics Lecturers

Credits to the Team


The idea of compiling this book is to benefit all medical students who are studying in UM and all
of us, as the MBBS batch 2012/2017, had made this book in hope that it would continue to benefit
our juniors from generation to generation. It is my greatest honour to have everyone of you in the
team in contributing your valuable time and efforts and together, we all share the equal amount
of credits.

Jun Min, Em

Editorial Board:
Chief Editor : Em Jun Min
Co-Editors : Adrian Lim Jia Hwa Khoo Wan Thien Ooi Ying Shi
Audrey Lee Ying Shin Koay Zhong Lin Oon Chun Huat
Aun Yi Yang Koh Ee Yin (Audrey) Quek Ven Chin
Bryan Lee Yen Pei Kong Chen Xi Sherwin Johan Ng
Celia Low Fang Ying Kow Yun Shi Sia Jo Ee
Chan Pei Qi Lai Weng Wai Tan Bee Cher
Chan Xiao Min Leong Hui Ling Tan Hui Ting
Cheah Tian Phern Liew Hun Nee Tan Siang Lyn
Chen Chin Chern Lim Eng Seng Tay Tun Khong
Chew Ai Wie Low Qiong Cong Tee Wei Jie
Chian Xue Han New Ru Peng Teoh Yi Ming
Chuah Chun Wooi Ng Kar Aik Tung Yu Feng
Goh Saw Huan Ng Yun Hui Wong Hong Nang
Heng Kai Voon Ngio Yi Chen Yan Hui Xin
Hoh Wee Liam Ong Jin Xu See Toh Yiling (Yaslyn)
Jaclyn Tay Yi Ling Ooi Chieh Yin Yaw Mei Sim
Jasmine Low Chay Lee Ooi Sze Ting Yong Pei Yee
References

1. Ismail, Hussain Imam Hj Muhammad, Hoong Phak Ng, and Terrence Thomas. Paediatric
Protocols for Malaysian Hospitals. Ministry of Health, 2012.
2. Kliegman, Robert M. Nelson textbook of pediatrics. Saunders Elsevier, 2012.
3. Marcdante, K. J., & Kliegman, R. (2015). Nelson essentials of pediatrics (7th edition.).
Philadelphia: Elsevier/Saunders.
4. Lissauer, Tom, and Graham Clayden, eds. Illustrated textbook of paediatrics. Elsevier Health
Sciences, 2011.
5. Sidwell, Rachel U., and Mike A. Thomson, eds. Easy paediatrics. CRC Press, 2011.
6. Procopis, Peter G. Examination Paediatrics; A Guide to Paediatric Training. Journal of
Paediatrics and Child Health 43.4 (2007): 322-322.
7. World Health Organization. Pocket book of hospital care for children: guidelines for the
management of common illnesses with limited resources. 2013 Revised Edition. Available at:
http://whqlibdoc. who. int/publications/2005/9241546700. pdf. (2015).
8. Maconochie, I., Bingham, R., Eich, C., López-Herce, J., Rodríguez-Núnez, A., Rajka, T., &
Biarent, D. (2015). European resuscitation council guidelines for resuscitation 2015 section 6
Paediatric Life Support. Resuscitation, 95, 222-247
9. Florin, Todd, et al. Netter's Pediatrics. Elsevier Health Sciences, 2011.
10. Buja, M. L., & Krueger, G. R. F. (2013). Netter's Illustrated Human Pathology Updated Edition
(2nd ed.). London: Elsevier Health Sciences.
11. Lee W. S., Thong M. K., Wong C.P. Handbook of Hospital Paediatrics. 289 pages. 2005,
UniPress Publishing.
12. CPG for the Management of Childhood Asthma (p.20). (2014).
13. CPG for the Management of Transfusion-Dependent Thalassaemia (p.99). (2009)
14. CPG for the Management of Neonatal Jaundice (p.62). (2014)

Disclaimer
According to the Malaysia Copyright Act 1987 section 13(2) and TRIPS agreement, this book is
intended for non-profit, educational purpose in view of the use of illustrations, diagrams or
tables from acknowledged reference sources. The amount of copyrighted materials used in this
book is minimal and appropriate to achieve a non-profit transformative purpose in favour of fair
use. However, to avoid any deprivation of authors` rights for all the original sources being used
by this book, its use should only be confined for each individual without any other commercial
purpose. Therefore, students are advised to refer and purchase these original books enlisted in
the `References` section for a more detailed explanation or for browsing of the related contents.
All editors would not held responsibility for any unauthorised distribution of this book in which
fair use would no longer applicable with regards to the use of materials from original sources.
Table of Content

Topics Page No.


PART I : CLINICAL PAEDIATRICS
- REFERENCE RANGES 1
- HISTORY TAKING 6
- PHYSICAL EXAMINATION
- GENERAL 11
- CARDIOVASCULAR SYSTEM 14
- RESPIRATORY SYSTEM 17
- GASTROINTESTINAL SYSTEM 19
- NEUROLOGICAL SYSTEM 23

PART II : FUNDAMENTALS OF PAEDIATRICS


- IMMUNISATION 29
- DEVELOPMENTAL ASSESSMENT (DA) 34
- FAILURE TO THRIVE (FTT) 45
- INFANT FEEDING 50
- MALNUTRITION 54
- MICRONUTRIENTS DEFICIENCY 57
- PREMATURITY 60
- PAEDIATRICS BASIC & ADVANCED LIFE SUPPORT (PBLS & PALS) 63

PART III : NEUROLOGY


- DOWN`S SYNDROME 75
- MENINGITIS 85
- ENCEPHALITIS/ ENCEPHALOPATHY 96
- CEREBRAL PALSY 99
- FEBRILE CONVULSION & SEIZURE 109
- EPILEPSY 113
- NEURAL TUBE DEFECTS 119
- HYDROCEPHALUS 123
- NEUROCUTANEOUS DEFECTS 125
- MUSCULAR DYSTROPHY 128

PART IV : CARDIOLOGY
- CONGENITAL HEART DISEASE 130
- RHEUMATIC FEVER 149
- INFECTIVE ENDOCARDITIS 155
- KAWASAKI`S DISEASE 160
PART V : RESPIRATORY
- COMMON RESPIRATORY INFECTIONS 163
- UPPER RESPIRATORY TRACT INFECTIONS (URTI) 165
- VIRAL CROUP 170
- ACUTE EPIGLOTTITIS 173
- ACUTE BRONCHIOLITIS 175
- BRONCHIAL ASTHMA 179
- PNEUMONIA 187
- PERTUSSIS (WHOOPING COUGH) 194
- CYSTIC FIBROSIS 196
- BRONCHOPULMONARY DYSPLASIA (BPD) 204

PART VI : GASTROENTEROLOGY
- ACUTE GASTROENTERITIS (AGE) 205
- DEHYDRATION & ELECTROLYTE IMBALANCES 212
- GASTROESOPHAGEAL REFLUX DISEASE (GERD) 217
- INFLAMMATORY BOWEL DISEASE (IBD) 219
- HIRSPRUNG DISEASE 228
- INTUSSUSCEPTION 230
- PYLORIC STENOSIS 232
- MALROTATION & VOLVULUS 233
- MECKEL`S DIVERTICULUM & MESENTERIC ADENITIS 234

PART VII : UROLOGY


- RENAL ANOMALITIES 235
- RENAL ASSESSMENT 239
- URINARY TRACT INFECTION (UTI) 240
- VESICOURETERIC REFLUX (VUR) 248
- HAEMOLYTIC URAEMIC SYNDROME (HUS) 250
- PROTEINURIA & HAEMATURIA 251
- ACUTE GLOMERULONEPHRITIS (AGN) 252
- NEPHROTIC SYNDROME 257

PART VIII : HAEMATOLOGY


- HAEMOPOIESIS 263
- ANAEMIA IN CHILDREN 264
- IRON-DEFICIENCY ANAEMIA 269
- THALASSAEMIA 271
- HAEMOSTASIS 284
- AUTOIMMUNE THROMBOCYTOPENIC PURPURA (AITP) 290
- HENOCH-SCHONLEIN PURPURA (HSP) 293
- SICKLE CELL ANAEMIA 295
PART IX : ONCOLOGY
- OVERVIEW 298
- LEUKAEMIA 305
- LYMPHOMA 315

PART X : INFECTIOUS DISEASES


- DENGUE FEVER 318
- MEASLES (RUBEOLA) 327
- MUMPS 330
- RUBELLA 332
- HHV INFECTIONS 334
- HERPES SIMPLEX 334
- CHICKENPOX & SHINGLES 336
- EBV 339
- CMV 340
- ROSEOLA INFANTUM & HHV-8 341
- ERYTHEMA INFECTIOSUM (FIFTH DISEASE) 342
- HAND, FOOT AND MOUTH DISEASE (HFMD) 343

PART XI : NEONATOLOGY
- CONGENITAL HYPOTHYROIDISM 344
- NEONATAL HEPATITIS SYNDROME 349
- NEONATAL JAUNDICE 353
- RESPIRATORY DISTRESS SYNDROME (RDS) 375

PART XII : ENDOCRINOLOGY


- TYPE 1 DIABETES MELLITUS (T1DM) 381

PART XIII : DYSMORPHISM


- ANGELMAN SYNDROME 391
- CORNELIA DE LANGE SYNDROME 392
- DANDY WALKER SYNDROME 393
- DIGEORGE SYNDROME (22q11.2 DELETION) 394
- GOLDEN HAR SYNDROME 395
- MARFAN SYNDROME 396
- NOONAN SYNDROME 397
- PRADER-WILLI SYNDROME 398
- RUSSELL-SILVER SYNDROME 399
- TURNER SYNDROME 400
- WILLIAMS SYNDROME 401

INDEX 402


PART I

CLINICAL PAEDIATRICS
Reference Ranges

Age Groups:
Neonates (≤ 28 days)
Infants (0-1 year old)
Toddlers (1-3 years old)
Pre-schooler (3-5 years old)
Grade-schooler (5-12 years old)
Adolescent (12-19 years old)
Young Adults (20-24 years old) * No longer considered Paediatric patient after 18 years old

Normal Ranges (PR, SBP, RR):

Pulse Rate (PR) Systolic Blood Respiratory Rate (RR)


Pressure (SBP)
Neonates & Infants 110-160 bpm 50-85 mmHg 30-50 /min
Toddlers 110-160 bpm 80-95 mmHg 25-35 /min
Pre-Schooler 110-160 bpm 80-100 mmHg 25-30 /min
Grade-schooler 80-120 bpm 90-110 mmHg 20-25 /min
Adolescent 60-100 bpm 100-120 mmHg 15-20 /min

Weight:
- First 7-10 days loses 10-15% body weight
- Regain birth weight by 7-10th day To calculate:
- First 3 months weight gain by 20-25 gm/day 1 - 9 years old : Wt (kg) = (Age + 4) x 2
- Double birth weight by 5 months 7 - 12 years old : Wt (kg) = Age x 3
- Triple birth weight by 1 year of age.

Length & Height (after 2 years old):


Birth to 1 year : 25 cm
- At birth 50 cm
1-3 years : 10 cm/ year
- 6 months 68 cm
3 yeas - Puberty : 5 – 7 cm
- 1 year 75 cm
- 2 years 85 cm
- 3 years 95 cm Mid-Parental Height:
- 4 years 100 cm - Boys = [Dad`s Ht + (Mum`s Ht +13)] / 2
- 5-12 years 5 cm/year - Girls = [(Dad`s Ht - 13) + Mum`s Ht] / 2
- Target Ht = Mid-parental Ht +/- 8 cm
Head Circumferences:
- Rate of CSF production : 0.35 ml/min = 500 ml/day
- At birth 30-35 cm
- < 3 months +2 cm/month
- 4-6 months +1 cm/month First year +12 cm (42-47 cm)
- 6-12 months +0.5 cm/month Second year +2 cm (44-49 cm)
- 1-2 years +2 cm/year
- 2-7 years +0.5 cm/year
- 7-12 years +1/3 cm/year

1
Tanner Pubertal Staging:
Male
1) Genitalia Development (G)

Stage I The testes, scrotal sac, and penis have a size and
proportion similar to those seen in early childhood.
Stage II There is enlargement of the scrotum and testes
and a change in the texture of the scrotal skin. The
scrotal skin may also be reddened, a finding not
obvious when viewed on a black and white
photograph.
Stage III Further growth of the penis has occurred, initially
in length, although with some increase in
circumference. There also is increased growth of
the testes and scrotum.
Stage IV The penis is significantly enlarged in length and
circumference, with further development of the
glans penis. The testes and scrotum continue to
enlarge, and there is distinct darkening of the
scrotal skin. This is difficult to evaluate on a black-
and-white photograph.
Stage V The genitalia are adult with regard to size and
shape.

2) Pubic Hair Development (P)

Stage I Vellos hair appears over the pubes with a degree of


development similar to that over the abdominal
wall. There is no androgen-sensitive pubic hair.
Stage II There is sparse development of long pigmented
downy hair, which is only slightly curled or
straight. The hair is seen chiefly at the base of
penis. This stage may be difficult to evaluate on a
photograph, especially if the subject has fair hair.
Stage III The pubic hair is considerably darker, coarser, and
curlier. The distribution is now spread over the
junction of the pubes, and at this point that hair
may be recognized easily on black and white
photographs.
Stage IV The hair distribution is now adult in type but still is
considerably less that seen in adults. There is no
spread to the medial surface of the thighs.
Stage V Hair distribution is adult in quantity and type and
is described in the inverse triangle. There can be
spread to the medial surface of the thighs.

2
Female
1) Breast Development (B)

Stage 1 Only the papilla is elevated above the level of the


chest wall.
Stage 2 Breast Budding. Elevation of the breasts and
papillae may occur as small mounds along with
some increased diameter of the areolae.
Stage 3 The breasts and areolae continue to enlarge,
although they show no separation of contour.
Stage 4 The areolae and papillae elevate above the level of
the breasts and form secondary mounds with
further development of the overall breast tissue.
Stage 5 Mature female breasts have developed. The
papillae may extend slightly above the contour of
the breasts as the result of the recession of the
aerolae.

3) Axillary hair development (A)


Stage 1 No hair
Stage 2 Some hair
Stage 3 Adult hair pattern

2) Pubic Hair Development (P)

Stage 1 Vellos hair develops over the pubes in a manner


not greater than that over the anterior wall. There
is no sexual hair.
Stage 2 Sparse, long, pigmented, downy hair, which is
straight or only slightly curled, appears. These
hairs are seen mainly along the labia. This stage is
difficult to quantitate on black and white
photographs, particularly when pictures are of
fair-haired subjects.
Stage 3 Considerably darker, coarser, and curlier sexual
hair appears. The hair has now spread sparsely
over the junction of the pubes.
Stage 4 The hair distribution is adult in type but
decreased in total quantity. There is no spread to
the medial surface of the thighs.
Stage 5 Hair is adult in quantity and type and appears to
have an inverse triangle of the classically feminine
type. There is spread to the medial surface of the
thighs but not above the base of the inverse
triangle.

3
Reporting Tanner Staging:
Male`s stage G(1-5), P(1-5), A(1-3) + Testicular volume (2-25 ml)
Female`s stage B(1-5), P(1-5), A(1-3) + Menarche

Puberty
Male
- Testicular enlargement (> 3mls Prader Orchidometer or > 2.5cm in longest diameter)
- Penile growth and pubic hair
- Growth spurt at P4 (testes at 10-12mls) at average 14 years [Late event]
- Growth completed when bone age is 16 years.

Female
- Breast development
- Growth spurt, B and P 2-3 (average 12 years) [Early event]
- Pubic hair and axillary hair
- Menarche: 13 years (10-14), Bone age 13 years, Tanner B & P3-4.
- After menarche little growth left (2-5cm)
- Growth completed when bone age is 14 years.

Guthrie`s Test
- Neonatal heel-prick screening for selective diseases.
- Mnenomics (Children Can Present More Seriously)
- Congenital hypothyroidism (TSH)
- Cystic fibrosis (Immunoreactive trypsinogen using dried blood)
- Phenylketonuria
- Maple Syrup Urine Disese (MSUD)
- Medium-Chain Acyl-CO-A Dehydrogenase Deficiency (MCADD)
- Sickle-cell anaemia

Fluid Requirement
Neonate
Day 1 : 60 mls/kg/day
Day 2 : 90 mls/kg/day
Day 3 : 120 mls/kg/day
Day 4 : 150 mls/kg/day (Same until 6th months)
6 months - 1 year : 120 mls/kg/day

After 1 year,
1st 10 kg : 100 mls/kg
2nd 10 kg : 50 mls/kg
Subsequent kgs : 20 mls/kg

4
History-Taking
Dr Revathi MD (USM), MPaeds (UM), Fellowship (Oncology)
Prof Surendran MD (UK), MB BCh BAO (UK), MRCPCH (UK), Fellowship (Respiratory)

Clean Hands
Introduce yourself
Informed consent & rapport

Biodata:
- Name, Gender, Age
- Date of Birth (DOB), Date of Admission (DOA)
- Informant like parents, caretakers, guardians (Reliability)

Presenting/Chief Complaint:
- Max 3 complaints, preferably only one complaint eg. Fever for 5 days prior to admission

History of Presenting Complaint:


- SOCRATES
- Site (Localisation, pain worst felt area)
- Onset (When? Duration?)
- Character (Intermittent/continuous; Productive, Blood, Frequency)
- Radiation (Pain either sharp, dull, acute, chronic) to anywhere?
- Alleviating factors (Medication, posture)
- Timing (Diurnal, Nocturnal)
- Exacerbating factors (Any triggering factors)
- Severity (eg. can speak in full sentence?)
- Associated symptoms?
- Chronological order
- eg. 5 years old female presented with fever and cough for 3 days
- DDx:
- URTI
- Pneumonia
- Asthma
- (Acute bronchitis -> If less than 2 y/o)
Cough, fever for 3 days Asthma Diarrhoea for 3 days
- Any bleeding - Any nocturnal symptoms - Duration
- Cyanosis episode - Any wheezing - Frequency of diarrhoea
- Difficulty in breathing - Occurrence of eczema - Colour of stool
- Post-tussive vomiting - Family history of atopy - Consistency
- Facial congestion - Any allergy to seafood - Any vomiting
- Worsen at night - Any carpet, pets exposure - Any sick contact?
(Sleep disturbance) - Any other precipitating
- Any sick contact? factors (cold, dust etc)
- Urination problem

- Oral intake (solid/ liquid)


- Activity (any lethargy)

5
Systemic Review: (To rule out)
- CVS - VSD/ASD, heart failure
- GIT – LOA/LOW, Jaundice
- CNS – Altered behaviour, seizure
- GUS (Genitourinary) – Increased frequency, Dysuria

Past-Medical History:
- Disease & Presentation
- Time of diagnosis, who diagnosed and where?
- Reason on previous admission
- Investigation done (What was done?)
- Treatment (compliance, control, complications) & Follow up
- Current status (well/poor controlled)
- Any planning surgery/procedure

6
- Not to be missed:
- Cyanotic heart disease & VSD/ASD
- Cystic fibrosis
- eg. Underlying history of VSD (heart failure) currently admitted for AGE
- PC focusing about AGE vomiting history (post-tussive), frequency
- eg. History of VSD (heat failure) admitted for respiratory distress
- PC: Difficulty in breathing HPOI: VSD history
- eg. Cerebral palsy child admitted with aspiration pneumonia, seizure, bed sore, electrolyte
imbalance prior to poor oral intake
- PC: Aspiration pneumonia & seizure HPOI: Cerebral palsy

Past-Surgical History:
- Important for VSD, cerebral palsy
- VP Shunt (hydrocephalus)
- Laparotomy (GI problems)

Paediatrics History:
- Antenatal
- Maternal medical conditions
- DM, HPT, Heart failure, Hyperthyroidism, Anemia-any supplement taken
- Infective screening (VRDL, HepB, HIV, CMV)
- Intrauterine growth restriction
- Symmetrical ht,wt, HC <3rd centile -> Occurs at 1st trimester (Microcephaly)
- Asymmetrical ht,wt <3rd centile; HC>3rd centile -> Occurs at 2nd/3rd trimester (PIH, GDM)
- Ultrasound findings, Blood group

- Intra-partum
- Delivery
- EMLSCS/ELSCS
- SVD (Any induction/ assisted delivery)
- When born? POG? Term or Preterm
- Baby weight LBW (1.5-2.5kg), VLBW (1-1.5kg), ELBW (<1kg)
- Apgar score (Ask whether baby cry/activity when born/ appear blue when born)
- Complications (Require resuscitation, Meconium-stained liquor)

- Post-partum
- Meconium Aspiration Syndrome (MAS)
- Ventilator, Duration, Oxygen supply, Complications like jaundice
- Neonatal Jaundice (NNJ) -> Kernicterus -> Cerebral palsy
- Pathological (<24hrs of life, >2 weeks of life - Persisted)
- Physiological (D2 to 2 weeks of life)
- Onset, Phototherapy, Exchange transfusion
- Baby blood group
- G6PD (From cord blood) – Cannot discharge until 5-10 days dt peak onset on 4-5 days
- Thyroid function (From cord blood) - Starts thyroxine treatment for hypothyroidism
within 2 weeks, if persists more than 1 month without treatment -> Mental retardation

7
Immunisation History:
- Details (Age, Dose, Duration, Follow immunisation chart, Complications)
- Completed immunisation (Up-to-date)
- eg. Baby at 4 months
- Baby has completed immunisation (up-to-date) by receiving BCG, HepB on birth, 2nd dose of
HepB on 1st month, 2nd dose of Hib, DPT, IPV on 2nd month, 3rd dose of Hib, DPT, IPV on 3rd
Month without any complications
- Possible complications (Local reaction, fever, rash, allergy, cellulitis/hematoma)

Developmental History: (Mainly for congenital causes)


Gross Motor Fine Motor Speech/Language Social
- Rolling over - Reach for own toys - Start to babble - Afraid of stranger
- Sit with support - Take small objects - Able to call `Papa` - Toilet-trained
- Stand & walk - Hold pencils - Able to speak few - Dry by day/night
- Up & down stairs - Play cubes words one sentence - Play with other child
- Pedal tricycle - Draw shapes - Know 1-10, A-Z - Attend own toilet need

Family History:
- Draw Family tree
- Take note for any siblings presented with same problems
- Ask about consanguinity

Social History:
- Father/Mother occupation
- Income (any financial problem?)
- Housing area/environment/electric & water supply
- Smoking/alcohol history (parent & patient)
- Academic performance (Special school/Normal school)
- Exam result (Good/excellent/average/poor) eg. ranking, interested subjects
- Extracurricular activities (important for chronic diseases eg. asthma)
- Sibling rivalry (Sick attention, relationship/coping, low self-esteem/emotional status)
- Social (Interaction with friends, Hobbies, Acitivity limitation, Mobility support, Support group,
Caretaker - who spends most time with child?)

8
Diet History:
- Breastfeeding history (Exclusive for 6 months)
- Weaning diet (Semi-solid food >6 months)
- Current diet
- If on milk, how many Oz/scoop each time?
- Normal/balanced adult diet
- Malnutrition (Adjusted diet)
- Cystic fibrosis (No fatty foods)
- Failure to thrive (how often)

Drug History:
- Drug, frequency, compliance, complications/side effects (eg. Lipodystrophy, local infection)
- Who observes/supervises patient when taking medicine

Summary:
- Age, Gender, Chief complaint
- Associated significant aspects of history
eg. Assoc with global developmental delay or Incomplete immunisations
- Give provisional and differential diagnosis

9
Physical Examination (General)
Dr Revathi MD (USM), MPaeds (UM), Fellowship (Oncology)

1) Approach
2) Patient Consent
- Opportunistic (Depending on child coorperation)
3) Anthropometry chart/parameters
- Based on serial parameters on centile chart
- 3rd, 5th, 25th, 50th, 75th, 95th, 97th Centile (CDC)
- Below 3rd centile (CDC) = 2 SD below mean (WHO)
- 1 centile = 2/3 of an SD
- Height, Weight -> Plot up to 18 yrs old
- Head Circumference (HC) -> Plot up to 3 yrs old
- Female (Pink/Green), Male (Blue)
- Separate own charts for Down syndrome,Turner`s
syndrome, Achondroplasia, VLBW (<1.5kg)
- Reason for dropping in centile? Refer pg. 44
- Nutrition deficiency, family conflicts/neglect,
serious infections (eg. pneumonia, meningitis)
- Reason of dropping & crossing ≥2 centile?
- Failure to thrive FTT, malabsorption syndrome
* Malaysia doesn`t have own growth chart but using WHO ones
4) Vital Signs
- Blood Pressure, Pulse Rate, Respiratory Rate (Refer Reference Ranges)
- Temperature (same as adult) : 36.5 - 37.5`C
- Normal BP in neonates 60/40 – 50/30 mmHg (If 90/60 is hypertensive in neonates)
- Lowest acceptable normal SBP for 5th centile = (Age x 2) + 70 = ___ mmHg
- Appropriate cuff size (2/3 of arm) for adult, children, infant, neonate
- Smaller arm -> Hypertension (overestimate)
- Bigger arm -> Hypotension (underestimate)
- Change in BP is indicated in loss of fluid (kidney disease), septic shock, hypovolemic shock
- Plot on BP centile charts

Age Height SBP DBP


Centile 25 th
50th 95th
25 th
50th 95th
1 y/o 25th
50th 60 80 100 20 40 60
75th
95th
Interpretation:
25th centile BP : 60/20mmHg (less than this is hypotension)
50th centile BP : 80/40mmHg
95th centile BP : 100/60mmHg (more than this is hypertension)
- Normal BP range is 60/20 – 100/60 mmHg
- If more than 99th centile BP requires urgent intervention

Hypertension is defined as average SBP and/or DBP that is >95th percentile for gender, age & height on
at least 3 separate occasions. (Normal SBP & DBP is <90th percentile) -Handbook of Hospital Paediatrics
10
General Inspection:

- Activity indicates severity


- Conscious level
- Assess using Glasglow Coma Scale (GCS)
- Motor (6), Verbal (5) & Eye (4) Max 15/15 Min 3/15
- <8 requires intubation, cannot maintain airway (eg. aspiration pneumonia)
- Motor:
- If cannot lift arm by ownself, stimulate pain sensation at sternum or supraorbital ridges
- Infant moves spontaneously or purposefully (6)
- Infant withdraws from touch (5)
- Infant withdraws from pain (4)
- Abnormal flexion to pain for an infant (decorticate response) (3)
- Extension to pain (decerebrate response) (2)
- No motor response (1)
- Verbal:
- Smiles, orients to sounds, follows objects, interacts (5)
- Cries but consolable, inappropriate interactions (4)
- Inconsistently inconsolable, moaning (3)
- Inconsolable, agitated (2)
- No verbal response (1)
- Eye:
- Opens eyes spontaneously (4)
- Opens eyes in response to speech (3)
- Opens eyes in response to painful stimuli (2)
- Does not open eyes (1)

- Appearance
- Color (poycythaemia/pallor/pink/cyanosis)

- Dysmorphic features
- Head (flat occiput/low set ears: >1/3 of ear is above line parallel to inner canthus/
skin tags/deformed pinna/hypertelorism: nasal bridge is more than single-eye diameter)
- Eye (cataract/squint/blue sclera/coloboma: hole in eye structures eg iris, retina, choroid,
optic disc/aniridia: no iris)
- Neck (web neck: excessive skin folds in Down/Turner`s syndrome)
- Skeletal deformity: syndactyly/polydactyly (webbed toes)/ bifid thumb/ absence thumb/
absence toe/Arachnodactyly/Ectrodactyly/Brachydactyly (clubbed thumb)/Acheiropodia/
Ectromelia (Phocomelia, Amelia, Hemimelia)/Arthrogryposis/ varus (club foot)/ Pigeon toe/
valgus (flat feet)/ Pes cavus/ Rocker bottom foot/ Hammer toe
- Skin changes: hypopigmentation/hyperpigmentation (café au lait spot): dt neurocutaneous
stigmata, inherited CNS disease eg. Sturge-weber syndrome (AD, Portwine stain),
Neurofibromatosis, Tuberous sclerosis
- Spine: Spina bifida

11
- Hand
- Finger clubbing, peripheral cyanosis, capillary refill time, koilonychia, leukonychia,
- Splinter haemorrhage, Osler`s node, Janeway lesions
- Dystrophic nails in Rheumatic heart disease
- Pulse (Rate, rhythm, volume, character)

- Forearm/Arm
- Birth marks, scratch marks, bruises
- Epitrochlear lymph nodes

- Eyes
- Scleral jaundice, conjunctival pink/pallor

- Oral cavity
- Dental hygience
- Hydration level (AGE, vomiting, diarrhoea)
- Glossitis (nutrition deficiency)
- Angular stomatitis (iron deficiency)
- Mouth ulcer
- Central cyanosis (respiratory & cardiac disease)

- Neck
- JVP/thyroid mass/lymph nodes (submental, submandibular, pre/post auricular, occipital,
anterior/posterior cervical, supraclavicular lymph nodes)

- Limbs
- Clubbing, dystrophic nails, oedema, deformity
- eg. CTEV (Congenital talipus quinovarus/club foot)

- Back
- Spina bifida, sacral oedema

12
Physical Examination (Cardiovascular System)
Dr Revathi MD (USM), MPaeds (UM), Fellowship (Oncology)

1) Approach
2) Patient Consent
- Opportunistic (Depending on child coorperation)
3) Positioning patient at 45’
4) Growth
- If Small for Age `I would like to confirm by plotting on the growth chart appropriate for the
age and gender`

Peripheral Examination
General Inspection:
- Activity
- Conscious level - Assess using modified Glasglow Coma Scale (GCS)
- Appearance
- Dysmorphic features

`I would like to proceed my examination further.`

- Hand
- Finger clubbing, peripheral cyanosis, capillary refill time, koilonychia (if needed)
- Splinter haemorrhage, Osler`s node, Janeway lesions
- Dystrophic nails in Rheumatic heart disease, Palmar erythema
- Pulse (Rate, rhythm, volume, character)

- Forearm/Arm
- Birth marks, scratch marks, bruises
- Collapsing pulse (Aortic regurgitation, Patent Ductus Arteriosus, Hyperdynamic circulation)
- Radio-radial delay (Subclavian artery stenosis, Pre-ductal coarctation of aorta - Left UL delay)
- Radio-femoral delay (Post-ductal coarctation of aorta - Lower Limbs delay)
- Pulse volume (normal flow with reduced volume, not always delayed)
- Femoral pulse no delay but with coarctation? Aortic stenosis (pulse weaker)
- Blood pressure (hypotension/hypertension)
- 4 limbs BP (UL, LL): difference in blood pressure in UL, LL*

- Eyes
- Scleral jaundice, conjunctiva pallor
- Conjunctival polycythaemia (Hct very high)
- Congenital cyanotic heart disease - chronic hypoxia eg. Tetralogy of Fallot (ToF),
transposition of great arteries (TGA), trunchus arteriosus (problem with heart anatomy,
mixing of oxygenated and deoxygenated blood > body compensate by producing more RBC
- Acyanotic heart disease - L>R shunt in interventricular septum
- Eisenmenger syndrome : VSD (heart failure) > Pulmonary hypertension (R>L shunt)
- can be cyanotic and acyanotic heart disease

13
- Oral cavity
- Dental hygience, dental caries (Infective endocarditis), high-arch palate (Marfan`s syndrome),
angular stomatitis (iron deficiency), central cyanosis (respiratory & cardiac disease), hydration

- Neck
- JVP (examine only if more than 5 to 6 years)
- Lymph nodes (submental, submandibular, pre/post auricular, occipital, anterior/posterior
cervical, supraclavicular lymph nodes)
- Limbs
- Clubbing, dystrophic nails, oedema, deformity
- Right lateral thoracotomy
- Back - Modified BT shunt,
- Spina bifida, sacral oedema - Lung (lobectomy)
- Tracheosphageal fistula repair
CVS Examination - Left lateral thoracotomy
- Modified BT shunt
Precordium
- Coarctation repair
- Scar (Refer table beside)
- PDA ligation
- Chest asymmetry (Precordial buldge) - Pulmonary artery (PA) banding
- Chest deformity (Pectus excavatum, Pectus carinatum) - Lung (lobectomy)
- Whether patient is tachypnic (subcostal, intercostal, - Median sternotomy
suprasternal recession) - Any bypass surgery
- Calculate Respiratory Rate (RR) - Look for previous chest drain
- Any visible pulse (Apex beat pulsation) sites, mediastinal drain sites,
- Dilated veins pacemakers
- Pacemaker box (Bulging)
- Mechanical prosthetic heart valve (Audible clicking sounds)

Palpation
- Warm hands (normal apex beat for paeds at 4th intercostal space, midclavicular line)
- Both hands palpate for apex beat (Not miss out dextrocardia)
- Thrill (4 areas)
- Parasternal heave at left sternal edge (Right ventricular hypertrophy)
- Palpable P2 at pulmonary area (Pulmonary hypertension)
- Suprasternal notch thrill (AS - carotid radiation)

Ascultation
- Mitral, Tricuspid, Aortic, Pulmonary areas
- Murmurs (grade, systolic/diastolic, radiation, best heard, maneuvers-inspi/expiration) 6 grades
- Grade 3 Murmur heard, without thrill
- Grade 4 Murmur heard, with thrill
- Mitral regurgitation (not common in paediatrics, often older dt cardiomyopathy,incompetence,
infections, radiate to axilla)
- Ventricular septal defect (common in children, pansystolic murmurs, not radiate to axilla)

What condition in paediatric children with MR? Acute Rheumatic Fever


My provisional diagnosis is mitral regurgitation secondary to acute rheumatic endocarditis, my
differential will be ventricular septal defect, but the point against it is that the murmur radiates to
axilla and patient is older age group. (Give two possibilities)

14
- Usually VSD will close by itself at age at 10 y/o, surgival intervention when too large > Heart
failure, pulmonary hypertension
- Mitral area (MR, VSD) common in paediatrics
- Tricuspid area (TR) rarely happen in children, mainly adult and IVDU (Infective endocarditis)
- Pulmonary areas (loud 2nd heart sound, any fixed 2nd heart sound – not alter by respiration or
posture)
- Listen murmur at the back
PS murmur – Ejection systolic murmur (mild), if severe might have no murmur
PDA murmur – Continuous murmur
Coarctation of aorta murmur
4 Cardinal Signs of Heart Failure:
Pulmonary atresia - No valve, no murmur
- Tachycardia
- Listen to lungs for bibasal crepitations
- Tachypnea
- Feel for pulsatile liver and hepatomegaly
- Cardiomegaly
- Back for deformity, scar and radiation
- Hepatomegaly
Describe heart sounds:
- First and second heart sounds dual rhythm, normal intensity (no loud 2nd heart sound or no
added sound), no murmurs

Common Diseases in Paediatrics:


- Congenital heart disease

Arteriovenous shunt
- Right pulse weaker than left pulse (unlike coarctation whereby right stronger than left)
- Look for any scar (shunt) behind axillary region
- Shunt connecting subclavian artery to pulmonary artery to bypass pulmonary stenosis/atresia
- Volume is smaller in right pulse as it splits into half
- Shunt murmur can be heard during ascultation at the area, if absent indicate shunt blockage.

Tetralogy of Fallot:
- *Pulmonary stenosis (most severe) -> no blood flow to lung
- Overriding of aorta
- Right ventricular hypertrophy
- Ventricular septal defect

In uncoorperative child/easily crying child:


- Ascultation is done first in paediatrics for murmurs, then only feel for apex beat, thrill
- Liver and lung then proceed to peripheral examination

For patient who are cyanosed always related to tachypnoea?


False, why?
- Only when there is ventilation-perfusion problem in
- Cardiac failure
- Pneumonia
- Severe hypoxia
- Metabolic acidosis (tissue perfusion is compromised)

15
Physical Examination (Respiratory System)
Dr Revathi MD (USM), MPaeds (UM), Fellowship (Oncology)

1) Approach
Signs of Respiratory Distress:
2) Patient Consent
- Grunting
- Opportunistic (Depending on child coorperation) - Nasal flaring
3) Positioning (45` or Sitting position) - Tracheal tug
- Intercoastal/subcoastal/
Peripheral Examination supraclavicular recession
General Inspection - Head bobbing
- Alert, conscious - Tachypnoea
- Active to surrounding - Tachycardia
- Appearance (Cyanosis/pink) - Use of acessory muscle
- Lethargic
- On any oxygen or IV drip (not important in CVS, mainly for hydration, unless poor oral intake or
patient has polycythaemia, sluggish blood flow > stroke, dilute the blood by volume-volume
transfusion)
- Dysmorphic features
- Any audible sounds (stridor/ wheezing)
- Nasal flaring (in respiratory distress)
- Calculate Respiratory Rate (RR) tachynoea?

- Hand
- Finger clubbing (suppurative lung disease, chronic lung abscess, pneumonia)
- Palmar crease pallor
- Pulse (Rate, rhythm, volume, character)
- Bounding pulse in CO2 retention

- Forearm/Arm
- Blood pressure taking
- Visible scars

- Eyes
- Scleral jaundice, conjunctiva pallor

- Oral cavity
- Dental hydration, central cyanosis (respiratory & cardiac disease)

- Neck
- JVP (indicated only when more than 5 to 6 years)
- Lymph nodes (submental, submandibular, pre/post auricular, occipital, anterior/posterior
cervical, supraclavicular lymph nodes)
- Nasal polyps (end of examination)

- Limbs
- Clubbing (unlikely in lower limb)
- Skin infections (2` immunodeficiency eg. Kartagener syndrome, Cystic fibrosis, Gluten ds)

16
Chest Examination
Inspection
- Scar (Medial sternotomy, lateral thoracostomy, Chest drain for chest tubes)
- Chest asymmetry (Precordial buldge)
- Chest deformity (Pectus excavatum, Pectus carinatum)
- Whether patient is tachypnic (subcoastal, intercoastal, suprasternal recession)

Palpation
- Apex beat (needed if suspect for mediastinal shift)
- Tracheal deviation (5- 6 y/o)
- Chest expansion (above, upper and lower chest wall)
- Tactile fremitus

Percussion
- Supraclavicular, Intercostal spaces (comparing both sides)
- Hyperinflation of lungs when loss of:
- Liver dullness on percussion (Liver ptosis)
- Cardiac dullness on percussion

Ascultation
- Bell for supraclavicular, Diaphragm for all areas
- If very subtile then only request for deep inspiration
- Breath through the mouth
- `99` vocal fremitus

Back
- Hug pillow to avoid scapula occulding ascultation
- Ascultate for all lung areas (compare bilaterally)
- Breath through the mouth
- `99` vocal fremitus

End of examination,
- Observe any nebuliser attached to patient
- Sputum pot
- Aerochamber (chamber with mouthpiece, take 10 breaths), Inhaler (salbutamol) indicates
asthmatic patient)
- Creon (small tablets) - exogenous enzymes for pancreatic deficiency, indicates cystic fibrosis

Common Diseases in Paediatrics: How to differentiate between mass and pleural


- Acute broncholitis (<18 months) effusion?
- Asthma (18 months to 1 year, >1yrs) - Both will push trachea away
- Pneumonia - Dull on percussion in mass, stony dull in
- Lung abscess pleural effusion
- Pleural effusion - Vocal fremitus louder in mass, softer in pleural
effusion (fluid)

17
Physical Examination (Gastrointestinal System)
Dr Revathi MD (USM), MPaeds (UM), Fellowship (Oncology)

1) Approach
2) Patient Consent
- Opportunistic (Depending on child coorperation)
3) Positioning patient lying flat with single pillow
4) Growth
`I would like to confirm by plotting on the growth chart appropriate for the age and gende`r

Peripheral Examination
General Inspection:
- Activity indicates severity
- Conscious level
- Appearance
- Dysmorphic features
- Nasogastric tube feeding (cannot swallow, have reflux, GI problem)

`I would like to proceed my examination further.`

- Hand
- Finger clubbing (liver cirrhosis, IBD - UC, CD)
- Leuconychia, Muehrcke`s lines (chronic liver disease, hypoalbuminaemia)
- Koilonychia (iron deficiency)
- Palmar erythema (chronic liver disease, polycythaemia, thyrotoxicosis)
- Pallor (GI blood loss, malabsorption, chronic liver disease)

- Forearm/Arm
- Birth marks
- Bruises (clotting abnormalities)
- Petechiae (hypersplenism)
- Scratch marks (pruritus in cholestatic/obstructive jaundice -> conjugated bile pigments
deposition to skin; uraemia)
- Spider naevi
- Pulse (rate, rhythm, volume, character) -> anemia, tachycardia
- Blood pressure (hypotension/hypertension)

- Eyes
- Scleral jaundice, conjunctiva pallor
- Kayser-Fleischer rings (Wilson disease)
- Xanthelasma (cholestasis, hypercholesterolaemia, liver disease)
- Cataract (TORCHES, Intrauterine infections -> conjugated jaundice + cataract + microcephaly)

- Oral cavity
- Oral hygience & hydration
- Glossitis (Vitamin B12 deficiency)
- Aphthous ulcer (Crohn`s disease)

18
- Angular stomatitis (iron deficiency anaemia)
- Palatal petechiae
- Blisters (small hematoma)
- Neck
- Skin colours (Pale - haematological malignancy; Fair, shallow complexion - chronic renal
failure hyperpigmented - chronic renal failure, thalassaemia; Jaundice - liver problem
- Lymph nodes (submental, submandibular, pre/post auricular, occipital, anterior/posterior
cervical, supraclavicular, Virchow lymph nodes) *End of Examination unless suspect lymphoma
- Chest:
- Spider naevi (bigger children)
- Gynaecomastia (bigger children)
- Any loss of axillary hair
- Limbs
- Ankle edema (Protein malnutrition, protein-losing enteropathy, 3rd space water accumulation)
- Scratch marks
- Bruises
Abdominal Examination GIT problem might be in either:
Abdomen - Hepatobiliary
- Abdominal distention - Genitourinary
- Scars - Haematological
- Umbilicus inverted/everted - Endocrine (Cushing`s syndrome,
- Dilated veins adrenal gland)
Palpation
- 9 quadrants eg. local tenderness over which quadrant
- `Do you feel pain any where?` - Last quadrant to be palpated (inform examiner patient is pain)
- Superficial Palpation: Tenderness, soft/guarding/rebound tenderness
- `Look at patient whether crying/pain`
- Deep Palpation: (organs-hepatosplenomegaly, any masses)
- Describe mass (site, size, shape, mobility, consistency, surface/margin, tenderness,
discharge, any skin changes) eg. pancreatic mass, bowel mass, lipoma, ill-defined mass
- Palpate for liver (fix hand, deep expiration moves, inspiration palpate)
- Percuss upper border, midclavicular line from angle of Louis
- Liver measurement (Liver is enlarged, _ cm below subcoastal margin at midclavicular line)
- >2 cm palpable liver is significant in >2 years old child
- Differentiate hyperinflation of lung (liver ptosis) or hepatomegaly
- Avoid using fingerbreadth, unless state how many cm
Describe:
There is a mass palpable below the right subcoastal margin at the right hypochondriac region
which moves with respiration inferiorly, smooth surface, sharp margin, extending to epigastric
region, nodular(cirrhosis)/smooth surface, hard/firm in consistency, non-tender, dull on
percussion, upper border is at ___th intercoastal space, __cm enlarged below right subcoastal
margin, cannot get above it.
Normal liver span: Newborn (~4.5-5 cm), 12 years of age (6-6.5 cm for females and 7-8 cm for males).
In between these times there should be appropriate linear growth with the child.
Adult (8-12 cm; female is 8-10 cm while male is 10-12 cm)

19
Describe:
There is a mass palpable over right hypochondrium region which is round in shape, upper border
is palpable, measuring __ cm, tender/non-tender, firm in consistency, mobile/non-mobile (any
attached overlying structure)

- Right hypochondrium masses (gallbladder eg. choledochal cyst, cholecystitis, choledocholithiasis)


- Palpate for spleen
- Examine inferiormedially from RIF towards left subcoastal margin
- If huge, feel for splenic notch (tip of the spleen)
- Percuss Traube`s space (normal is resonance, dull for splenomegaly)
- Palpate for kidney
- Bimanual palpation for balloting kidney
- Shifting dullness
- Percuss until dull, turn patient to right lateral side, wait for 10 seconds, percuss again
- Percuss on another side if left side there`s a mass present
- If both sides have masses, `There are masses in both flank region, therefore it`s difficult for me
to conclude whether there`s presence of ascites.
- Fluid thrill
- Patient with gross ascites
Ascultation
- Bowel sounds
- Renal bruits (renal stenosis)
Feel for inguinal lymph nodes (IBD, lymphoma, leukemia, abdominal/uterine mass/malignancy)
- Look for any hernia
- If cannot cough, look for site whether there`s any swelling/ bulging
Look for external genitalia
- Pubertal staging for pubic hair (~10 years old)
- Thalassaemia patient : Pubertal delay due to iron deposition/overload from recurrent blood
transfusion, causing panhypopituitarism
- Delayed breast development, absence pubic hair, behaving like pre-pubertal age
- Testicular size/volume (using orchidometer)
1-3ml: pre-pubertal stage
4ml: pubertal stage
- Palpate then compare with orchidometer, about how many mls, any delay in puberty
- Assess for hypopituitarism Causes of palpable kidneys:
- Scrotal edema (Nephrotic syndrome) Unilateral:
- Labia majora edema (Nephrotic syndrome) - Multicystic kidney
- Obstructed hydronephrosis
Back:
- Renal tumour (Wilms tumour)
Scars (Nephrostomy scar) - Renal vein thrombosis
Examine sacral region for sacral edema Bilateral:
Renal punch (rarely done in small children) - Polycystic kidneys (AR/AD)
- Tuberous sclerosis
I would like to complete my examination by - Renal vein thrombosis
doing/assessing:
- Pubertal staging
- Examine the chest (if not done)
20
- Lymph node examination
- Per-rectal examination
- Vomitus, stool (fatty, maleana/pale colour)
- Urinalysis (frothy urine in nephrotic syndrome; hematuria in acute glomerulonephritis)
- Urine dipsticks for proteinuria
- Temperature chart

Precocious puberty
Girls - Secondary sexual characteristics (breast & menses) developing < 8 years
- Menarche <10 years
- Mostly familial causes
Boys - Secondary sexual characteristics developing < 9 years
- Mostly pathological cause (congenital adrenal hyperplasia, intracranial
tumours, dysgerminomas

True precocious puberty False precocious puberty


- GnRH-dependent development of secondary - GnRH-independent development
sexual characteristics at a young age in a normal - May be an unusual progression of sexual
progression accompanied by a growth spurt, maturity
leading to full sexual maturity from activation of - Isolated premature thelarche, adrenarche and
the hypothalamic-pituitary-gonadal axis. menarche can occur.
- Causes: LH ↑, FSH ↑ - Causes: LH ↓, FSH ↓
- Familial - Adrenal (CAH, adrenal tumour)
- Congenital, eg. neurofibromatosis, - Gonadal (Ovarian tumour, testicular tumour)
hydrocephalus - McCune-Albright syndrome
- Acquired, eg. post-sepsis, surgery, radiotherapy - Exogenous steroids
- Brain tumours - Hypothyroidism

Physiologically, girls undergo 3 stages:


A) Thelarche (Breast development)
B) Adrenarche (Adrenal gland)
- Cortisol production
- Pubic hair, axillary hair development
C) Menarche (Commencement of menstruation, average age 12.2 years, occurs at B4)

Pathologically,
If girls have menarche first before hair/breast development, must suspect for Ovarian CA.

Physiologically, boys will have adrenarche, usually have testicular enlargement first, then only
have pubic hair, axillary hair development and hoarseness of voice

Pathologically, if boys have moustache, axillary and pubic hair without testicular enlargement
- Testosterone is not produced by testis, but produced externally eg. malignancy, pituitary
changes

21
Physical Examination (Neurological System)
Dr Revathi MD (USM), MPaeds (UM), Fellowship (Oncology)
Dr Ang Hak Lee MD (UKM), MPaeds (UM), Fellowship (Cardiology)

5 main components of CNS: Localisation of the lesion:


- Motor & Sensory (UL, LL) - UMN/LMN
- Cerebellar Sign - CNS/PNS/Muscle
- Cranial nerve examination - Tone, Power, Reflex, Coordination, Sensory
- Microcephaly & Macrocephaly (TPRCS)
- Developmental assessment/milestones

1) Approach
2) Patient Consent
- Opportunistic (Depending on child`s coorperation)
3) Inspection (Mostly)

Peripheral Examination
General Inspection:
- Activity movement, floopy/active
- Conscious level
- Assess using modified Glasglow Coma Scale (GCS)
- Motor (6), Verbal (5) & Eye (4) Max 15/15 Min 3/15
- Appearance
- Color (poycythaemia/pallor/pink/cyanosis)
- Facial asymmetry, one-eye ptosis, drooling of saliva
- Dysmorphic features
- Microcephalic
- Macrocephalic (increase CSF, increased brain parenchyma or congenital malformation)
- Hydrocephalus (dilated ventricles, not necessary macrocephalic, can be microcephalic in
congenital toxoplasmosis associated with cerebellar atrophy + hydrocephalus)
- Environment
- External Ventricular Drainage (EVD) - hydrocephalus, draining of CSF
- Wheelchair/Clutches/Walking frame

`I would like to proceed my examination further.`

Listen to instructions
1) Examine the lower limbs
- Stand, expose properly to upper thigh
- Start with gait examination (ask patient to walk to-and-fro)
- Scissoring gait (cerebral palsy)
- Waddling gait (proximal myopathy)
- High-stepping gait (footdrop,peroneal nerve palsy),
- Hemiplegic gait (stroke, ask patient to walk on lateral sides of feet (Fog`s test) if there is
subtle hemiplegic gait)
- Broad-base gait (cerebellar ataxia)
- Parkinsonian gait
22
- Stamping gait (proprioceptive disorders)
- Apraxic gait (hydrocephalus)
- Antalgic gait (pain with weight-bearing)
- Psychogenic gait
- Ask patient to run, if cannot see any gait
- Tandem gait (balance in one line, dorsal column problem)
- Romberg`s sign (dorsal column, if ataxia, fall when close the eyes; cerebellar will fall
with/without closing eyes)
- Gower`s sign (Ask patient to squat and stand, in proximal myopathy like Duchenne Muscular
Dystrophy (DMD), patient will use shin to climb)
- Look at patient`s back for any swelling over spinal region, tuft of hair or observable scars
- If patient cannot walk, ask patient to stand and slowly sit down (assess mobility)
- Lie down
- Inspection
- Leg posture (Hip)
- Normal posture: internally rotated & abducted
- Cerebral palsy,scissoring gait: externally rotated & adducted
- Knee (flexed/no)
- Any muscle wasting (most commonly affect vastus medialis)
- Any scars (eg. muscle biopsy scar, archilles tendon scar for
contracture)
- Any deformity (fracture, nail changes, shortening of leg)
- Any skin lesions (hypopigmentation/hyperpigmentation)
- Look for muscle fasciculations (tapping)
- LMN lesion
- Look for muscle tone (start from proximal, relax and test for range of motion)
- hypertonia/hypotonia
- Test for clonus (involuntary movement of ankle, >5 is significant)
- perform sudden flexion at the ankle
- Test for power
0 No movement
1 Flickering of toes
2 Move sideway, cannot move against gravity
3 Move against gravity
4 Move against gravity with resistance (less strong)
5 Can resist fully (strong)
- `Can u touch my hand with your toes?`
- Proximal muscle weakness (proximal power is about _/5)
- Distal muscle weakness (distal power is about _/5)
- Test for reflexes (knee, ankle, plantar reflexes - upgoing is UMN, downgoing is normal)
- Do Jendrassic maneuver if little movement
- Barbinski`s sign only elicit up to 1 month infant (unless persistent primitive reflex)
- Test for sensory dermatomes, ask patient to close eyes

23
- Head T2, Nipple T4, Umbilical T10.
- If lesion near T1-T2, patient will not be alive,
might be brain death
- Test for proprioception in dorsal column
- big toe up or down
- Examine the spine (if patient lying initially)
- spina bifida (LL paralysis, unable to walk)
- Palpate abdomen for
- Constipation (due to lower lumbar patho)
- Urinary incontenence (distended bladder)
- Look for any scars
- DDx for Hydrocephalus + Spina bifida:
- Arnold-chiari malformation
- Dandy-Walker syndrome

- When spina bifida is observed, must look for


ventriculoperitoneal shunt (VP shunt)
- Obstructive hydrocephalus (huge lateral ventricle
with narrowed interventricular foramen due to
increased ICP.
- Drain the ventricles and absorbed into omentum
- If patient with VP shunt + abdominal pain,
suspect complication from peritonitis (long-term)

2) Examine the upper limbs


- Inspection
- Abnormal hand posture
- Any muscle wasting
- Any scars
- Any deformity (fracture, nail changes)
- Look for muscle fasciculations (tapping)
- LMN lesion
- Look for muscle tone (start from proximal, relax
and test for range of motion)
- hypertonia/hypotonia
- Test for power (adduct,abduct,extension,flexion)
0 No movement
1 Flickering of toes
2 Move sideway, cannot move against gravity
3 Move against gravity
4 Move against gravity with resistance (less strong)
5 Can resist fully (strong)
- `Can u make a fist?` Try to release from patient`s hand, test for power
- Proximal muscle weakness (proximal power is about _/5)
- Distal muscle weakness (distal power is about _/5)
- Test for reflexes (biceps, triceps, brachioradialis/supinator reflexes)
- Do Jendrassic maneuver if little movement
- Test for sensory dermatomes, ask patient to close eyes
- Proprioception (big thumb)

24
- Test for coordination (cerebellar sign)
- For both UL & LL
- Ask patient to walk (broad-base gait,
ataxia)
- Past-pointing (dysmetria)
- Dysdiadochokinesia
- Holmes Rebound phenomenon
- Pendulum knee jerk
- Heel-shin test

3) Examine the cranial nerve


CNI (Olfactory nerve)
- Test for smell eg. coffee

CNII (Optic nerve)


- Visual acuity > Snellen chart, color test (red, blue, yellow, green)
- Visual field

CN III, IV, VI (Occulomotor,Trochlear,Abducens nerve)


- Pupillary and consensual reflex
- Accommodation
- Visual field `H-shaped`
- Bitemporal hemianopia
- Homonymous hemianopia
- Central scotoma
- Any restriction in movement: opthalmoplegia, diplopia, ptosis
- Lazy eye (unilateral poor vision)
- Paralytic/non-paralytic
- Visual evoke potential (VEP) if cannot assess eye movement at all

CN V (Trigeminal nerve)
- Motor
- Clench teeth, palpate masseter & temporal

25
- Close opened mouth, palpate medial pterygoid
- Sensory
- corneal reflex (both eyes blinking)
- facial sensation (3 divisions)

CN VII (Facial nerve)


- Look up for frowning of forehead and try to push down wrinkle
- Close eyes tightly and try to open
- Smile, look for nasolabial lesion
- Close lip tightly try to open
- Facial weakness, test buccinator by asking patient to blow, prick face using finger

CN VIII (Vestibulocochlear nerve)


- Rinne`s and Weber`s test
- Perform distraction test (student holding red ball, examiner stand at side, ensure child`s
vision has no problem)

CN IX, X (Glossopharyngeal, Vagus nerve)


- Open mouth and say `ahh` look for uvula deviation
- Cough/swallow (gag reflex)

CN XI (Acessory nerve)
- Shrug shoulder to feel for trapezius
- Turn head against resistance for sternocleidomastoid

CN XII (Hypoglossal nerve)


- Inspect tongue for any wasting & fasciculation
- Tongue deviation
- Power of tongue (pushing against hand in mouth)

Head Circumference (HC) – OSCE


- Rate of growth in preterm infants is 1 cm/week, but reduces with age.
- Head growth follows that of term infants when chronological age reaches term
- Head circumference increases by 12 cm in the 1st year of life
- 6 cm in first 3 months
- 3 cm in second 3 months
- 3 cm in last 6 months

In humans, the sequence of fontanelle closure is as follows:


- Posterior fontanelle generally closes 1-3 months after birth
- Sphenoidal fontanelle closes around 6 months after birth
- Mastoid fontanelle closes from 6-18 months after birth
- Anterior fontanelle generally close between 9-18 months

26
Localising signs (more significant in adolescent and adults):

Frontal lobe signs:


- Unsteady gait (unsteadiness in walking)
- Muscular rigidity, resistance to passive movements of the limbs (hypertonia)
- Paralysis of a limb (monoparesis) or larger area (hemiparesis)
- Paralysis head and eye movements
- Inability to express oneself linguistically, expressive aphasia (Broca's aphasia)
- Focal seizures which can spread to adjacent areas (Jacksonian seizure)
- Grand mal or tonic-clonic seizures
- Changes in personality such as disinhibition, inappropriate jocularity, rage without provocation; or loss
of initiative and concern, apathy, akinetic mutism, general retardation
- `Frontal release` signs, eg. reappearance of primitive reflexes such as the snout reflex, the grasp reflex,
and the palmar-mental reflex unilateral loss of smell (anosmia)

Parietal lobe signs


- Impairment of tactile sensation
- Impairment of proprioception eg. postural & passive movement sensation
- Sensory and visual neglect syndromes eg. inability to pay attention to things in certain parts of the
person's sensory or spatial environment, can be as extreme as denial of a limb.
- Loss of ability to read, write or calculate (dyslexia, dysgraphia, dyscalculia)
- Loss of ability to find a defined place (geographical agnosia)
- Loss of ability to identify objects based on touch (astereognosia)

Temporal lobe signs


- Deafness without damage to the structures of the ear, cortical deafness
- Tinnitus, auditory hallucinations
- Loss of ability to comprehend music or language, sensory aphasia (Wernicke's aphasia)
- Amnesia, memory loss
- Other memory disturbances such as deja vu complex
- Multimodal hallucinations
- Complex partial seizures (temporal lobe epilepsy)

Occipital lobe signs


- Total loss of vision (cortical blindness)
- Loss of vision with denial of the loss (Anton's syndrome)
- Loss of vision on one side of the visual field of both eyes (homonymous hemianopsia)
- Visual agnosias eg. inability to recognize familiar objects, colors, or faces visual illusions such as
micropsia (objects appear smaller) and macropsia (objects appear larger)
- Visual hallucinations, displaying elementary forms, eg. zig-zags and flashes, in one half of the
visual field only for each eye. (In contrast, temporal lobe visual hallucinations display complex
forms, and fill the entire visual field.)

Limbic Signs
- Loss or confusion of long-term memory prior to focal neuropathy (Retrograde amnesia)
- Inability to form new memories (Anterograde amnesia)
- Loss/reduced emotions (Apathy)
- Loss of olfactory functions, decision making ability

Cerebellar signs
- Unsteady and clumsy motion of the limbs or torso (Ataxia)
- Inability to coordinate fine motor activities (Intention tremor & Dysmethria)
- Inability to perform rapid alternating movements (Dysdiadochokinesia)
- Involuntary left-right eye movements (Nystagmus)
- Hypotonia, Dysarthria, Heel-shin test, Scanning/staccato speech
27
PART II

FUNDAMENTALS OF
PAEDIATRICS
Immunisation
Definition:
Vaccine Any suspension of antigen which is intended to produce protective immunity
in the host after administration.
Toxoid Modified biological toxin which is rendered non-toxic but maintains its ability
to provoke an immune response.
Adjuvant/Conjugate Compount linked to a vaccine to enhance the immune response in the host.
Most common eg aluminium salts
Live attenuated Live suspension of microorganisms which have been rendered non-virulent but
vaccine retain their infectivity (multiply) and immunogenicity (antigenic) in the hos.
They generally confer long-lasting immunity.
Attenuated strains that are almost or completely devoid of pathogenicity. They
multiply in host cells and induce antigenic stimulation
- Cellular immunity -> T-lymphocytes
- Adaptive immunity (humoral) -> B-lymphocytes -> Plasma cell -> Abs ->
Memory B & T cells -> Active immunisation -> Lifelong immunity
Killed vaccine Purified extracts from live organism which are incapable of replcation and
therefore non-infectious. They induced relatively short period of protective
immunity.

MOH Schedule
Age (Months) School years
0 1 2 3 5 6 9 10 12 18 4yrs 7yrs 13yrs 15yrs
BCG 1 *
Hep B 1 2 3
DTaP 1 2 3 B
IPV 1 2 3 B
Hib 1 2 3 B
Measles(Sabah)
MMR 1 2
JE(Sarawak) 1 2 3 4
HPV 3X*
DT B
TT
* For BCG, injection given at age of 7 if no scar.
3X* For HPV, 3 doses within 6 months (0,1, 6) at age of 13.
In UM, Pentaxim vaccine is given (DTPa-IPV + Hib) together

Mode of Administration:
- BCG (Intradermal), Others (IM/SC). All are killed vaccines except MMR, BCG, OPV (Polio).
- Many vaccines (inactivated or live) can be given together simultaneously (does not impair
antibody response or increase adverse effect). But they need to be given at different sites unless
given in combined preparation which avoid multiple injections to child. (eg. DTaP, IPV, Hib)
- Site of administration:
- Oral : (Rotavirus, Live typhoid vaccines)
- Intradermal (ID) : BCG, Left deltoid area (Proximal to insertion of deltoid muscle)
- Deep SC, IM injections : ALL vaccines except the above
- Anterolateral aspect of thigh : Preferred site in children
- Upper arm : Preferred site in adults
- Upper outer quadrant of buttock : Associated with lower antibody level production

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Contraindications:

A) Absolute contraindication for any vaccine


- Severe anaphylaxis reactions to previous dose of the vaccine or to a component of vaccine.
- Postponement during acute febrile illness (minor infection without fever or systemic upset is
NOT a contraindication).

B) Relative contraindication for any vaccine


- Within 2 weeks of elective surgery (avoid vaccination)

C) Absolute contraindications for live vaccine


- Immunosuppressed children (malignancy, irradiation, leukaemia, lymphoma, primary
immunodeficiency syndromes but NOT asymptomatic HIV)
- On chemotherapy or < 6 months after last dose
- On high-dose systemic steriods (eg. Prednisolone ≥ 2 mg/kg/day for > 7 days)
- On low-dose systemic steriods (eg. Prednisolone > 2 weeks) : Delay vaccination for 3 months
- If topical/inhaled steriods OR low dose systemic < 2 weeks or EOD (every other day) for > 2
weeks, can administer live vaccine.
- Another LIVE vaccine is given including BCG < 4 weeks ago (Give live vaccine simultaneously,
if unable then give separately with a 4-week interval)
- Within 3 months following IV Ig (11 months if given high-dose IV Ig eg. Kawasaki disease, ITP,
GBS, immunocompromised exposed to other infectious diseases)
- Pregnancy (live vaccine is theoretical risk to fetus) UNLESS there is significant exposure to
serious conditions like polio or yellow fever in which case the importance of vaccination
outweights the risk to the foetus.

D) Absolute contraindications for killed vaccine


- Generally safe except in SEVERE local (induration involving >2/3 of the limbs) or severe
generalised reactions in the previous dose.

E) Following are not contraindications to vaccination


- Mild illness without fever (eg mild diarrhoea, cough, runny nose)
- Asthma, eczema, hay fever, impetigo, heat rash (avoid injection in affected area)
- Treatment with antibiotics or locally acting steriods.
- Child`s mother is pregnant.
- Breastfed child (does not affect polio uptake).
- Neonatal jaundice.
- Underweight or malnourished.
- Over the recommended age.
- Past history of pertussis, measles or rubella (unless confirmed medically)
- Non-progressive, stable neurological conditions like cerebral palsy, Down syndrome, simple
febrile convulsions, controlled epilepsy, mental retardation.
- Family history of convulsions.
- History of heart disease, acquired or congenital.
- Prematurity (immunise according to schedule irrespective of gestational age)

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F) Special Contraindications

BCG - Not to be given to symptomatic HIV infected children


Hep B - Severe hypersensitivity to aluminium or thiomersal (not needed for
HbsAg or Ab positive.
Pertussis - Progressive neurological diseases like infantile spasm, tuberous sclerosis
- Severe reaction to previous dose
- Anaphylaxis
- Collapse or shock-like states
- Hyporesponsive states
- Fits and fever within 72 hours
- Severe local reaction involving 2/3 limbs
- Static neurological diseases, developmental delay, personal or family history
of fits are NOT contraindications.
- Severe hypersensitivity to aluminium and thiomersal.
DT&T - Severe hypersensitivity to aluminium and thiomersal.
Polio - Diarrhoea & vomiting
- Hypersensitivity to penicillin, neomycin, streptomycin or polymycin
- Within 3 weeks from a proposed tonsillectomy (remote risk of vaccine-
induced bulbar polio)
- Polio (IPV) is to be used for immunocompromised children, their siblings and
household contacts. OPV if given to immunocompromised or HIV positive
children tend to cause prolonged excretion of the OPV and can be hazardous
to caregiver.
MMR - Severe reaction to hen`s eggs or neomycin.
Measles - If < 9 months old presence of maternal Ab may decrease immunogenicity
- Avoid in persons hypersensitive to neomycin, polymyxin OR anaphylaxis to
egg ingestion.
Rubella - Contraindicated in pregnancy (though no reported cases of congenital
rubella syndrome due to vaccine)

Footnotes:
1. For infants < 6 wks age, use Recommended Immunisation Schedule for Infants & Children.
2. Measles vaccine should be given only after 9 mths. (exception - given at 6 months in Sabah)
3. For special groups of children with no regular contact with Health Services and with no immunisation
records, BCG, HBV, DTaP- Hib-IPV and MMR can be given simultaneously at different sites at first
contact.
4. It is not necessary to restart a primary course of immunisation regardless of the period that has elapsed
since the last dose was given. Only the subsequent course that has been missed need be given. (eg. An
infant who has been given IPV1 and then 9 months later comes for follow-up, the IPV1 need not be
repeated. Go on to IPV2.). Only exception is Hepatitis A vaccine.
5. Vaccination programme changed in Oct 2008 from OPV (lived) to IPV (killed) as polio wild type
no longer endemic in Malaysia, preventing OPV S/E of paralytic disease.
6. Transplacental transfer of maternal Ig lasted in body around 6 months, avoid giving lived vaccine
except in Sabah for measles. For testing vertical transmission of infection, measure IgG only after 6
months.
7. At birth the immune system of baby is immature, pre-term baby is more prone to infection. At 36th
POG, maternal Ig will pass to fetus via placenta, level will be reduced by 4-6 weeks postnatally.

30
Possible Side Effects from Vaccination:

BCG - Local reaction: Papule at site of vaccination occurs within 2-6 weeks. This
grows and flattens with scaling and crusting. Occasionally a discharging ulcer
may occur. This heals leaving a BCG scar of ≥4 mm in successful vaccination.
- BCG adenitis may occur.
Hep B - Local reaction. Fever and flu-like symptoms in 1st 48 hours. Rarely erythema
multiforme or urticaria.
DPT - Local swelling and redness within 24-72 hours lasting 1-2 weeks.
- Acute encephalopathy (0-10.5/million)
- Shock and unusual shock-like state (3.5-250/100,000)
- Anaphylaxis (2/100,000 cases)
- Protracted crying (0.1-6%)
DT & T - Swelling, redness, pain.
- A small painless nodule at injection site (harmless).
- Transient fever, headache, malaise, rarely anaphylactic reaction.
- Neurological reactions rare.
OPV - Vaccine associated paralytic polio (VAPP)
IPV - No serious side effects have been documented, except local reaction.
- Indicated for children with severe immunocompromised conditions (eg. 1`
and 2` eg HIV, malignancy, organ transplant)
Measles - Transient rash in 5% cases.
- Fever between D5-D12 post vaccination lasting 1-3 days.
- URTI symptoms.
- Febrile convulsions (D6-D14)
- Encephalopathy within 30 days (1/100,000 cases)
- SSPE (1/1,000,000 cases) incidence of acquired infection is 6-22/1,000,000)
Mumps - Rarely transient rash, pruritus, purpura.
- Parotitis in 1% of vaccines, ≥3 weeks after vaccination.
- Orchitis and retrobulbar neuritis very rare.
- Meningoencephalitis is mild and rarely occur (1/800,000) natural infection is
1/400)
Rubella - May have rash, fever, lymphadenopathy, thrombocytopenia, transient
peripheral neuritis.
- Arthritis and arthalgia occurs in up to 3% children and 20% adults who
receive the vaccine.
- Rarely polyneuropathy (like GBS)
Hib - Local swelling, redness and pain soon after vaccination and last up to 24
hours in 10% of vaccines.
- Malaise, headache, fever, irritability, inconsolable crying. Very rarely seizure.

Special Circumstances:

A) Measure to protect inpatients exposed to another inpatient with measles:


- Protect all immunocompromised children with HNIG 0.25-0.5 mls/kg. (measles may be fatal in
children in remission from leukaemia)
- Check measles immunisation status in other children. Give measles monocomponent vaccine
to unimmunised children within 24 hrs of exposure.
- Discharge inpatient child with uncomplicated measles.
- Notify health office.

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B) Patient with past history or family history of febrile seizures, neurological or developmental
abnormalities that would predispose to febrile seizure:
- Febrile seizure may occur 5 to 10 days after measles (or MMR) vaccination or within the first 72
hours following pertussis immunisation.
- Give PCM (120mg or ¼ tablet) prophylaxis after immunisation (esp DPT) 4-6 hourly for 48 hours
regardless of whether the child is febrile.
- This reduces the incidence of high fever, fredfulness, crying, anorexia and local inflammation.
- Rectal diazepam may need to stand by for patient with previous febrile convulsions.

C) Closed contacts of immunodeficient children and adults must be immunised, particularly


against measles and polio (use IPV)

D) Patient contact with invasive Haemophilus influenza B disease


- Immunise all household, nursery or kindergarden contacts < 4 years old.
- Household contacts should receive Rifampicin prophylaxis at 20 mg/kg OD (Max 600 mg) for 4
days (except pregnany women – give one IM dose of cetriaxone)
- Index case should be immunised irrespective of age.

E) Children with Asplenia (elective or emergency splenectomy, asplenic syndrome, sickle cell
anaemia) are susceptible to encapsulated bacteria and malaria.
- Pneumococcal, Meningococcal A, C, Y & W-135, Haemophilus influenza B vaccine.
- For elective splenectomy/chemotherapy/radiotherapy: Give vaccine preferably ≥ 2 weeks
before procedure. However, they can be given even after the procedure.
- Penicillin prophylaxis should continue ideally for life. If not until 16 years old for children or 5
years post-splenectomy in adults.

F) Babies born to mothers who are HbsAg OR HbsAg positive should be given Hepatitis B Ig (200
IU) and vaccinated with the Hepatitis B vaccine within 12 - 48 hours. Given in different syringes
and at different sites.

G) Premature infants may be immunised at the same chronological age as term infants.

Factors affecting efficacy of vaccines:


- Timing (if given too early, maternal Ab circulating infant will interfere with
development of immune response; if given too late, infant may develop disease
before vaccine is given; Consideration needed for places with high incidences like
measles in Sabah)
- Dose (excessive dose will increase cost and risk of side effects)
- Interval between doses (For vaccine requiring booster dose, the recommended
minimum interval between doses is 1 month. No max interval between doses. If
subsequent dose is missed, immunisation can be continued and no need to repeat
the first dose.
- Maintaining in cold chain (production, transportation until administration, suitable
temperature & storage conditions should be maintained)
- Correct administration route (BCG for intradermal, others IM/IV)
- Combination vaccine (convenience, better acceptance and compliance by parents)

32
Developmental Assessment (DA)

Definition:
- Development is the progressive, orderly, acquisition of skills and abilities as a child grows. It is
influenced by genetic, neurological, physical, environmental and emotional factors.
- Main objectives:
- Assess the differing of child development potential by age
- Early detection of delay or abnormal development
- Provide therapy promptly
- Constitutes of 4 aspects (Gross motor, Fine motor, Speech/language, Social) + Primitive reflexes

Important points to note:


- Child must be coorperative, not tired, fretful, hungry nor sick. Remember child behave differently
in an unfamiliar environment.
- Allowance must be made for prematurity up to 2 years.
- Take note of parental account of what child can or cannot do.
Note parental comments on abnormal gait, speech defects, etc.
- Normal development is dependent on intergrity of child`s hearing and vision.
- Normal pattern of speech and language development is essential for a normal social, intellectual
and emotional development.
- Delay in development may be global eg affecting all areas equally or specific areas only eg oro-
motor dysfunction causing speech delay.
- Advanced motor development does not signify mental superiority. Manipulative skills are more
reliable guide, as well as interest in surrounding, responsiveness, alertness and concentration.
- Always assessvision, hearing, language and social development in addition to gross and fine
motor skills.
- Always rule out hypothyroidism in all cases of global developmental delay.
- For preterm child, assess the developmental age by calculating it from EDD -> Corrected age
(Correction is not require when >2 years old)

Warning Signs:
- Discrepant head size or crossing centile lines (too large or too small)
- Persistence of primitive reflexes > 6 months.
- No response to environment or parent by 12 months
- Not walking by 18 months.
- No clear spoken words by 18 months.
- No 2 word sentences by 2 years.
- Problems with social interaction at 3 years.
- Congenital anomalies, odd facies.
- Any delay or failure to reach normal milestones.
* Parental concerns must always be taken seriously.

A) Assessment of children with suspected developmental delay:

History
- Consanguinity
- Family history of developmental delay

33
- Maternal drugs, alcohol, illness and infection in pregnancy
- Prematurity, perinatal asphyxia
- Severe neonatal jaundice, hypoglycaemia or seizures
- Serious childhood infections, hospital admissions or trauma
- Home environment conditions (environmental deprivation)

Physical examination
- Head circumference, dysmorphic features
- Neurocutaneous markers
- Neurological abnormalities
- Full developmental assessment

Investigations
Consider:
(individualised according to history, physical
- Hypothyroidism
findings)
- Chromosomal anomaly
- Visual and auditory testing
- Cerebral palsy
- T4, TSH
- Congenital intrauterine infection
- Chromosomal Analysis
- Congenital brain malformations
- Consider
- IEM (Inborn errors of metabolism)
- Creatine kinase in boys
- Autistic spectrum disorder
- MRI Brain
- Attention deficit hyperactivity
- Metabolic screen
disorder (ADHD)
- Specific genetic studies
- Prior brain injury, brain infections
(Fragile X, Prader Willi or Angelman syndrome)
- Neurocutaneous disorders
- Refer to a geneticist
- Duchenne`s muscular dystrophy
- EEG if history of seizures

B) Assessment of children with suspected hearing impairment or speech delay:

History Warning Signs for Hearing Impairment


- Congenital infection 1 Child appears not to hear
- Perinatal medications 2 Child makes no attempt to listen.
- Severe neonatal jaundice 3 Does not respond to name, `No` or clue
- Family history of deafness or speech delay words e.g. `Shoe`, by 1 yr age
- Chronic ear infections 4 Any speech/language milestone delay
- Quality, quantity of speech Consider:
- Congenital sensorineural deafness
Physical Examination - Familial, genetic deafness
- Examine ears - Congenital rubella infection
- Dysmorphic features - Oro-motor dysfunction
- Distraction test
- Assess expressive, receptive speech
- Neurological/ developmental assessment

Management
- Formal hearing assessment
- Speech-language assessment and interventions
34
HearingTests at different ages
Age Test Comments
Newborn Automated Otoacoustic Determines cochlear function. Negative
screening Emission (OAE) test test in conductive hearing loss, middle ear
infections, or in moderate to severe
sensorineural hearing loss.
Any age Brainstem Auditory Evoked Measures brainstem responses to
Responses (BAER) sound. Negative test in sensorineural
hearing loss
7-9 months Distraction Test (DT) Determines response to sound whilst
presented during a visual distraction.
Infants Behavioural Observation Audiologist identifies bod- ily reactions to
Assessment (BOA) test sound, i.e. cessation of activity, body
movement, eye widening and opening
suckling rate.
> 2.5 years Conditioned Play Audiometry Earphones placed on child and various
games are done when test tone is heard.
Older Children Pure Tone Audiometry Patient presses a response button or
(~4 yrs old) raises a hand when the test tone is heard

C) Assessment of children with suspected visual impairment:

Risk factors Warning Signs for Visual Impairment


- Prematurity 1 Does not fix on mother`s face by 6 wks
- Intrauterine infections (TORCHES) 2 Wandering or roving eyes after 6 wks
- Family history of cataracts, retinoblastoma 3 Abnormal head postures
or squint. 4 Leukocoria (white eye reflex)
- Previous meningitis, asphyxia.
5 Holds objects very close to eye.
- Dysmorphic babies.
6 Squint after 6 months of age.

D) Assessment of children with suspected learning difficulties:


It is sometimes a challenge to identify the primary cause of the learning difficulty as conditions
like dyslexia , ADHD and intellectual impairment share common symptoms.

History (A thorough history is important)


- Antenatal perinatal and postnatal complications
- High risk behaviour like substance abuse in mother
- Family history of development delay, learning difficulties etc.
- Detailed developmental milestones
- When learning problems were first noted (preschool achievement, etc. as children with
dyslexia or ADHD will have symptoms in early childhood)
- Past and current education performance
- Areas of learning difficulties
- Specific: e.g. reading difficulties (dyslexia) , writing difficulties (dysgraphia) but extremely
good in tasks that require visual stimulation, e.g. art, music

35
- General : more commonly seen in children with some degree of intellectual impairment or from
an extremely understimulated environment
- Strength of the child perceived by parents and teachers
- Who is the main caregiver at home?
- Social background of the family

Review School concerns with the patient, parents & teachers (always ask for teachers report)
- Common symptoms
- Apathy towards school
- Avoidance or poor performance in specific subject areas
- Disruptive or negative behaviour in certain classes

Review all school workbooks (not only report card)

Basic Cognitive (intellectual functioning) screening tool in a Pediatric Clinic :


- Ask child to tell about a recent event : birthday, visit to grandparents etc. (note whether
language is fluent, coherent, organized)
- Ask parents whether child has difficulty taking retaining classroom instructions or instructions
at home (short term memory)
- Observe the child using a pencil to copy symbols and words (visual perceptual motor disorder
characterized by confusing symbol, easy distractibility , inability to copy information)
- Ask the child to perform a 3-step command (sequencing ability to communicate and
understand information in a orderly and meaningful manner)
- Ask the child to repeat four words , remember them and repeat them again when asked in 5 –
10 minutes (memory , attention)
- Ask the child to repeat three, then four digits forward then repeat three, then four digits
backward (concentration)

Physical Examination
- Anthropometric measurement
- General alertness and response to surrounding (Children with dyslexia will be very alert and
usually very enterprising)
- Dysmorphism
- Look for neurocutaneous stigmata
- Complete CNS examination including hand eye coordination as children may have a associated
motor difficulties like dyspraxia
- Complete developmental assessment.
- Ask child to draw something he or she likes (this can help to get a clearer picture about intellect
of the child)

Block and Pencil test (From Parry TS: Modern Medicine, 1998)
Age Block Test Pencil Test
3 - 3.5 yrs Build a bridge Draw a circle O
3.5 - 4 yrs Draw a cross +
3 - 4.5 yrs Build a gate Draw a square
5 - 6 yrs Build steps Draw a triangle Δ
This test screens cognitive and perceptual development for age.
Block test: build the structure without child observing then ask the child to copy the structure.
Pencil test: Draw the object without child observing then ask the child to copy it.

36
Differential Diagnosis
Common Causes - Autism
- ADHD or combination of both
- Specific learning difficulty like dyslexia
- Limited environmental stimulation
Genetic/ chromosomal - Fragile X
disorder - Hypothyroidism
- Intellectual impairment
- Tourette
- Neurofibromatosis
Neurological - Seizures
- Neurodegenerative conditions
Miscellaneous - Anaemia
- Auditory or visual impairment
- Toxins (Fetal alcohol syndrome, prenatal cocaine
exposure, lead poisoning)

Plan of Management (Dependent on the primary cause for learning difficulties)


- Dyslexia screening test if available
- DSM 1V for ADHD or Autistic Spectrum Disorder (Refer CPG Management of children & adolescents with ADHD)
- Refer Occupational therapist for school preparedness (pencil grip, attention span etc) or for
associated problems like dyspraxia
- Refer speech therapist if indicated
- Assess vision and hearing as indicated by history and clinical examination
- Targeted and realistic goals set with child and parents
- One-to-one learning may be beneficial
- Registration as Child with Special Needs as per clinical indication after discussion with parents

Investigations
Clinical impressions guides choice. Consider:
- DNA analysis for Fragile X syndrome for males with Intellectual impairment
- Genetic tests, e.g. Prader Willi, Angelman, DiGeorge, Williams syndromes
- Inborn errors of metabolism
- TSH if clinically indicated
- Creatine Kinase if clinically indicated
- MRI brain study abnormal neurological examination
- EEG only if clinically indicated

When is IQ Testing Indicated?


When diagnosis is unclear and there is a need to determine options for school placement.


Global Developmental Delay (GDD)
- When a child has not reached two or more milestones in 4 domains of development

37
E) Primitive Reflexes
- Appear from birth and then lost as development progresses.
- High motor center will inhibit the reflexes in later life.
- Persistence beyond these age indicates failure of CNS maturation.

Age Absence of Primitive Reflex


2 - 4 months Palmar grasp, Stepping, Rooting, Sucking, Prone-crawl, Doll`s eye reflex
5 - 6 months Moro reflex, Asymmetrical tonic neck reflex (ATNR), STNR
7 - 8 months Crossed adductor reflex, Swimming reflex
9 - 12 months Plantar grasp (Barbinski reflex), Spinal Galant reflex *refer below

Primitive reflexes Descriptions


Palmar grasp It occurs when a finger is placed in neonate`s palm and the neonate
grasps the finger. This reflex disappears around 4-6 months. Signs of
rentention include poor fine motor skills, handwriting or manual
dexterity.
Plantar grasp It occurs when a finger is placed against the base of neonate`s toes and
the toes curl downward to grasp the finger. It disappears around 9-10
months.
Sucking reflex It is triggered by placing a finger or mother`s nipple in the infant`s
mouth. The neonate will suck the finger or nipple forcefully and
rhythmically in coordination with swallowing. It is inhibited similar with
rooting reflex at 3-4 months.
Rooting reflex When infant is stroked or touched on either side of mouth, the infant will
turn towards the source, open mouth and suck. It is inhibited at 3-4
months.
Moro reflex It occurs when an infant is lying in a supine position and stimulated by a
(Startle reflex) sudden movement. This stimulus results in a symmetrical extension of
the infant`s extremities while forming a C-shape with the thumb and
forefinger. This is followed by a return to a flexed position with
extremities against the body. Inhibition of this reflex occurs at 3-6
months. An asymmetrical response with this reflex may indicate a
fractured clavicle or a birth injury to the nerves of the arm. Absence of
this reflex in neonate is an ominous implication of underlying
neurlogical damage.

Asymmetrical Tonic It is activated as a result of turning the head to one side. As the head is
Neck Reflex (ATNR) turned, the ipsilateral arm and leg will extend while contralateral limbs
or Tonic labyrinthine will flex and bend, mimics a fencer. This reflex is inhibited by 6 months
reflex of agein the waking state. Its persistence beyond 8 to 9 months will
disable the baby to support the weight by straightening arms and
bringing knees beneath the body. Signs of retention include problem
with eye-hand coordination, crossing vertical midline, visual tracking.
Symmetrical Tonic It occurs with either the extension or flexion of the infant`s head.
Neck Reflex Extension of the head results in extension of arms and flexion of legs,
while flextion of head results in flextion of arms and extension of legs.
This reflex is inhibited by 6 months to enable crawling. Signs of retention
include tendency to slump while sitting, poor muscle tone, inability to sit
still and concentrate.

38
Barbinski or Plantar It is triggerd by stroking one side of the infant`s foot upwards from the
reflex heel and across the top of the foot. Infant responds by hyperextending
the toes, great toe flexes towards the top of the foot and the other toes
fan outwards. It generally inhibited 6-9 months postnatally.
Pupillary reflex It occurs with darkening the room and shining a pen-torch directly into
the neonate`s eyes for several seconds. The pupil should both constrict
equally. This reflex should not disappear.
Spinal Galant reflex It is stimulated by placing the infant on the stomach or lightly
supporting him or her under the abdomen with a hand and using a
fingernail, gently stroking one side of the neonate`s spinal column from
the head to the buttocks. The response is positive when neonate`s trunk
curving towards the stimulated side. This reflex can become inhibited
anytime between 3-9 months. Signs of retention include fidgeting,
bedwetting, poor concentration or short term memory, unilateral or
bilateral posture issues.
Doll`s eye reflex It is noted with infant in supine position, slowly turning the head to
either side. The infant`s eye will remain stationary. This reflex should
disappear between 3-4 months.
Prone-crawl reflex It can be stimulated by placing the neonate in prone (face down) on a
flat surface. The neonate will attempt to crawl forward using the arms
and legs. This reflex will be inhibtied by 3-4 months.
Swimming reflex It is stimulated when placing neonate face down in water, the neonate
will make corrdinated swimming movements. This reflex should
disappear at 6-7 months.
Landau reflex It is seen in horizontal suspension with the head, leg and spine
extended. If the head is flexed, hip, knees and elbows will also flex. It
appears about 4 to 5 months, disappear at 1 year old. Absence of this
reflex can occur in hypotonia, hypertonia or mental abnormality.
Parachute reflex It appears around 6-9 months and persist to adulthood. It is elicited by
holding the child in ventral suspension and suddenly lowering to the
couch, infant will react by extension of arms as defensive reaction. It will
be absent or abnormal in CP, asymmetrical in spastic hemiplegia.
Blinking reflex It is stimulated by momentarily shining a bright light directly into the
neonate`s eyes causing him or her to blink. It should not be inhibited.
Cough, Gag, Sneeze, These reflexes should not be inhibited but persisted into adulthood.
Yawn reflexes

39
Gross Motor Fine Motor
Age Descriptions Age Descriptions
6 weeks - Head lag, rounded back, head same plane as 6 weeks - Fix, focus and follow object to 90’
body (Pull to sit) - Follow object to 180` (Past midline)
- Raised chin, high pelvic, knees below abdomen 3 months - Hand grasp object loosely, not
(Ventral suspension) reaching out
3 months - Slight head lag, head above body - Reach for toy
5 months
- Good head control, head lift 45-90’ - No squint
- Pull self up - Palmar grasp (ulnar) of cube
6 months
4 months - Roll from Prone to Supine - Move head, eyes in all direction
5 months - Roll from Supine to Prone 7 months - Transfer object
- No head lag, sit straight back 9 months - Inferior pincer grasp (scissor grasp)
6 months - Sit with support, bear weight on legs, - Neat pincer grasp
support with hands 1 year old - Bang 2 cubes
7 - 8 months - Commander crawl (Creeping) - Tower of 2
9 months - Pull self to sit, sit steadily - Tripod grip
- Stand with support/holding - Flip page one by one
- Lean forward without pivot 1.5 year old - Scribbles spontaneously
- Visual test (Pie chart)
10 months - Pull self to stand - Tower of 3
11 months - Walk with both hand held - Imitates train cube without chimney
1 year old - LSCS (Lie, Sit, Crawl, Stand) 2 years old - Copies straight line
- Walk like a bear (one hand held) - Tower of 6
- Stand alone well - Hold pencil well
1.5 year old - Up & down stairs with one hand held - Imitates train cube with chimney
- Throw ball without falling 2.5 years old
- Copies straight lines - |
- Sit on chair - Tower of 8
2 years old - Up & down stairs (2 feet/step) - Imitates bridge cube of 3
- Walk backwards 3 years old - Copies circle
- Kick ball without falling - Tower of 9
2.5 years old - Jump on both feet - Copies square and plus
4 years old
- Walk on tip toes - Goodenough test 4
3 years old - Pedal tricycle - Copies cross and triangle
5 years old
- Up (1/step) & down (2/step) stairs - Goodenough test 8
- Stand on one foot for seconds - Copies diamond and complex square
4 years old - Up & down stairs (1 foot/step) 6 years old - Goodenough test 12
- Skip/hop on one foot - Tower of 10
5 years old - Skip on both feet
- Run on toes Speech/ Language
6 years old - Heel to toe walk
- Kick, run, climb Age Descriptions
6 weeks - Quiet & startle to sound
Social 8 weeks - Vocalising
Age Descriptions
- Squel with delight
6 weeks - Smile responsively 3 months
- Turn head around (ear level)
3 months - Social smile (Smile spontaneously)
- Babbling with single syllable
- Resist toy pull, smile at itself in mirror 6 months
5 months - Distraction test
- Mouthing
8 months - Babbling with combined syllable
9 months - Stranger anxiety
9 months - Localising sound above,below ear 1m
- Play `peek-a-boo’
- Understand phases
- Feed with spoon occasionally
1 year old - 2-3 words with meaning-papa,mama
- Understand `NO’
- Localising sound above head
1 year old - Casting & follow object
- Recognize >5 words, Picture card -1
- Drink, feed with cup, spoon but spills 1.5 year old
- Point 2-3 body parts
- Play ball with examiner
- Join 2-3 words into sentence
- Clap hands
2 years old - Point 4 body parts, Picture card - 3
- Toilet-trained
- Obey 4 simple commands
1.5 year old - Imitate housework
- Know full name & sex
- Drink & feed with cup and spoon 2.5 years old
- Name one colour
- Dry by day (put on shoes,socks,pant)
2 years old - Count to 10, form sentences
- Play near children 3 years old
- Name two colours, Nursery rhymes
- Unbutton, dress, undress with help
- Fluent conversation, ask questions
- Dry by night 4 years old
3 years old - Name three colours, A-Z
- Play with other children
- Know AGE, Fluent speech
- Parallel/interactive play
- Name four colours
- Buttons clothes fully 5 years old
4 years old - Triple order preposition
- Attend own toilet needs
- Tell time
- Dress/undress alone
5 years old
- Tie shoelaces

40
DENVER DEVELOPMENTAL SCREENING TOOL II (Malaysia Modified version)

Generally, Malaysian and Denver children appear to be similar in their development during first six years of life except for some minor differences in the
personal-social, language and gross motor sectors. Malaysians appear to be slower in self-care but more advanced in "helping around the house", "playing
interactive games" and in "separating from mother". They were slightly slower in gross motor function during first year of life but more advanced during the
second year of life. They were also slightly more advanced in language development. Differences can partly be explained by differences in socio-economic or
cultural differences or genetic factors between these two groups of children.

41
Denver`s Guide on Performing Developmental Assessment

42
Information needed during history taking of a child with suspected developmental disabilities:

43
Physical findings of a child with suspected developmental disabilities:

44
Failure to Thrive (FTT)
Definition:
- Reduction by ≥2 centiles on the weight and height plotted on growth chart.
- Growth parameters are persistently below 3rd centile.
- For WHO chart: <2 standard deviation (SD) below the mean for age
- It is a sign that describes underlying problem but NOT a diagnosis
- Rate of growth is significantly lower than that of other children of similar age and gender.
- Suboptimal weight gain or growth in infants or toddlers
Growth Chart:
- Ideally should be recorded from birth till 18 years old (weight, height) or 3 years old (HC)
- 3rd centile is the lower limit of normality (3% of normal children fall within this limit)
- Single plot is insufficient to interpret as FTT (can comment underweight) unless
- Markedly below 3rd centile
- Markedly discrepant from HC/ length
- Repeated observations are important to identify problems where change in weight is
compared with change in HD/ length
- Special chart needed for Down synrome, Turner syndrome
- Weight over 85th centile is considered overweight while over 97th centile is considered obese.
- Premature infants are plotted as `Corrected` age using the formula:
Corrected age = Gestational age - Number of weeks of prematurity (40 weeks POG as baseline)

- For example, 4 months baby (gestational age) born at 32th weeks POG (8 weeks from 40th
weeks) will have corrected age of 2 months (8 weeks).
- Corrected age is not required when
- Infant born at 36th weeks of POG onwards (not considered premature)
- Baby reaches 2 years old and should be plotted normally like any other child.
Specific Growth Patterns Requiring Further Evaluation:
Pattern Representative Diagnoses to Further Evaluation
Consider
Weight, length, HC all - Familiai short stature - Midparental heights
<5th percentile - Constitutional short stature - Evaluation of pubertal
- Intrauterine insult development
- Genetic abnormality - Examination of prenatal records
- Chromosomal analysis

Discrepant percentiles - Normal variant (familial or - Midparental heights


(eg. Weight 5th, length constitutional) - Thyroid hormone
5th, HC 50th etc) - Endocrine growth failure - Growth factors, growth
- Caloric insufficiency hormonal testing
- Evaluation of pubertal
development
Declining percentiles - Catch-down growth - Complete history & PE
- Caloric insufficiency - Dietary & social history
- Endocrine growth failure - Growth factors, growth
hormone testing

45
Aetiology:
Organic Non-organic
- Inadequate food intake - Inadequate food intake
- Inability to feed - Feeding problems
- Mechanical problem (eg. cleft palate) - Insufficient breast milk
- Lack of coordination (eg. cerebral palsy) - Poor breastfeeding technique
- Vomiting - Incorrect infant formula preparation
- GERD, pyloric stenosis - Insufficient food offered
- Chronic diseases causing anorexia - Lack of regular feeding time
- Respi (cystic fibrosis, asthma) - Infant hard to feed (resist
- CVS (congenital heard disease) feeding/disinterested)
- GIT (malabsorption, D, V, Crohn`s disease)
- Renal (UTI, CRF, Renal tubular acidosis) - Environmental deprivation
- Malignancy - Socioeconomic
- Low income
- Diminished food absorption - Poor education
- Protracted diarrhoea - Poor social support
- Short bowel synrome (post-operation) - Family dysfunction
- Small intestinal disease (Celiac disease) - Marital discord/ single parent
- Pancreatic disease (cystic fibrosis) - Maternal mental illness
- Post-necrotising enterocolitis - Alcohol/ drug abuse
- Child abuse/ neglect
- Protein-losing enteropathy
- Intestinal lymphangiectasia
- Milk protein intolerance (prolonged AGE)
- Inflammatory bowel disease (IBD)

- Increased energy requirement


- Malignancy
- Severe burns/ trauma
- Chronic diseases
- Thyrotoxicosis

- Metabolic
- Hypothyroidism
- Congenital adrenal hyperplasia (CAH)
- Amino acid & organic acid disorders

- Miscellaneous
- Chromosomal disorders (Down, Noonan,
Turner syndrome)
- Congenital infections

46
Clinical features:
Symptoms Signs
- Global developmental delay - Malabsorption
- Gross & fine motor skills - Respiratory
- Mental & social skills - CVS
- Delayed secondary sexual maturation - Neurological
(adolescent stage) - GIT (abdominal distention)
- Constipation (Poor feeding) - Renal (UTI, RTA, CRF - anaemia, sallow)
- Excessive sleepiness (Lethargy) - Physical abuse (eg. Bruises)
- Irritability - Dysmorphic features (underlying syndrome)
- Enlarged tonsils (OSA can lead to FTT)

History:
Birth History Intrauterine insults (IUGR), Prematurity, Birth weight, Infective
screening, Exposure toharmful agents (smoking, alcohol)
Past-Medical History Frequency of acute/chronic illness, Past-hospitalisations,
Previous medical conditions
Feeding History Quantity of milk consumed, Feed preparation, Weaning (when,
what & quantity), Dietary recall and diary
Family History Maternal & paternal height, Growth of other family members &
any illness in family (familial short stature)
Detailed Social History Parental( depression, marital disharmony, substance abuse,
unemployment, poverty) Food insecurity/shortage, Living
condition, Psychosocial problem, Abuse, Neglect

Physical Examination:
- Anthropometric (weight, height, HC - small for age; mid-arm circumference for skeletal muscle
mass; triceps skin-fold thickness for subcutaneous fat storage)
- Evidence of neglected hygiene (eg. diaper rash, unwashed skin, overgrown and dirty nails or
dirty clothing) or signs of non-accidental injury (NAI) or abuse (scars, bruises, ecchymoses)
- Dymorphic features, poor eye contact, lack of facial expression, absence of cuddling response
- Vital signs: hypotension(adrenal/thyroid insufficiency), hypertension(renal disease),
tachycardia/tachypnoea(increased metabolic demand)
- HEENT: Chronic otitis media(structural oro-facial defect), Cataracts(congenital rubella
syndrome, galactosemia), aphthous stomatitis(Crohn`s disease), Thyroid enlargement(hypoT)
- GI: Finger clubbing (Crohn`s disease), Leukonychia (hypoalbuminaemia), Rectum(empty
ampulla for Hirschsprung`s disease)
- Respi: wheezing (CF, asthma)
- CVS: murmur (congenital heart disease)
- Neuro: abnormal deep tendon reflex(CP), dysphagia(CN palsy)
- Uro: diaper rash (diarrhoea, neglect)
- Skin: Pallor(anaemia), Candidiasis(immunodeficiency), Eczema(allergy), Erythema nodosum
(ulcerative colitis, vasculitis)
- Behavioral: Uncooperative (difficult to feed)

47
Investigations:
Blood - FBC
- Anaemia (chronic disease, iron-deficiency, vitamin B12)
- Infections
- Inflammation & immune deficiency
- BUSE + creatinine (renal failure, RTA, metabolic disorders)
- VBG (for RTA - normal anion gap metabolic acidosis)
- LFT (liver disease, malabsorption, metabolic disorders) *ALP↑ osteoclastic activity
- TFT (hypothyroidism)
- Immunoglobulins (immunodeficiency)
- Anti-endomysial, anti-gliadin antibodies (celiac disease)
Urine - U-FEME + C&S (UTI, renal disease)
*Congo red stain for fat gobules under microscopy
Stool - Ova + cysts (worms/ parasitic infections)
- Faecal elastase (pancreatic insufficiency)
Karyotyping - Turner syndrome (short stature)

Others - CXR + sweat test (diagnose Cystic Fibrosis)


- Serum calcium, phosphate (Rickets)
- Lactate, pyruvate (IEM)
- Liver biopsy (glycogen storage disease)
- HIV test (immunodeficiency)

Management:
- Correction of underlying aetiology (if possible)
- Enteral or Parenteral feeding, follow up patient and monitor growth chart
- For patient with severe malnutrition, resuscitation protocol is indicated.

Resuscitation Protocol (based on IMCI, Unicef WHO)


- Indicated to those who fulfill the following criteria:
- Orang asli or other indigenous children present with history of being unwell, fever, diarrhoea, vomiting and
poor feeding
- Severe malnutrition
- Lethargy or has lost consciousness
- Shock
A) Initial assessment:
- Weight the child (or estimation)
- Measure vital signs (BP, PR, RR, temp)
- Provide oxygen support
- IV/intraosseous line
- Draw blood for investigations where possible (RBS, FBC, BUSE, blood culture, BFMP, ABG)
B) Resuscitation for shock
- Give IV/IO fluid 15 ml/kg over 1 hour (use 0.5 normal saline or Hartmann; use 0.5NSD5% if
hypoglycaemic)
C) Monitor and Stabilise
- Measure PR, RR every 5-10 minutes
- Start antibiotics IV Cefotaxime or Ceftriaxone (if N/A use Ampilicin+Chloramphenicol)
- Monitor blood sugar, prevent hypothermia
D) If there are signs of improvements (but PR, RR falling)
- Repeat IV/IO bolus 15 ml/kg over 1 hour
- Initiate ORS (or ReSoMal) PO at 10 ml/kg/hr
- Discuss case with Paediatrician and referral

48
E) If child deteriorates (RR +5/min or PR +25bpm or fails to improve with IV/IO fluid)
- Stop infusion as this can worsen child`s condition
- Discuss case with Paediatrician immediately and referral

Algorithm for Re-Feeding Plan (based on IMCI, Unicef WHO)

A) Starter feed with F75 based on IMCI protocol


- Feeds at 75-100kcal/kg/day (< 100kcal/kg/day in the initial phase).
- Protein at 1-1.5 g/kg/day
- Total volume 130mls/kg/day (if severe oedema, reduce to 100mls/kg/day).

B) How to increase feeds?


- Increase F75 gradually in volume (eg. 10 ml/kg/day in first 3-4 days)
- Gradual decrease in feeding frequency: 2, then 3 and 4 hourly when improves.
- Calculate calorie and protein content daily
- Consider F100 catch up formula when
- Calories 130/kCal-kg/day-140kCal/kg/day.
- Child can tolerate orally well, gains weight, without signs of heart failure.
Note: 1. In a severely oedematous child this process might take about a week. 2. If you do not increase calories and proteins
the child is not going to gain weight and ward stay will be prolonged.

C) Monitoring
- Avoid causing heart failure
- Suspect if: sustained increase (>2 hrs) of respiratory rate (increases by 5/min), and/or
heart rate by 25/min from baseline.
- If present: reduce feed to 100ml/kg/day for 24 hr then slowly increase as follows:
-15ml/kg/day for next 24 hrs; then 130ml/kg/day for next 48 hrs.
- Then increase each day by 10 mls.
- Ensure adequate weight gain
- Weigh child every morning before feeds; ideal weight gain is > 10g/kg/day
- If poor weight gain < 5g/kg/day do a full reassessment
- If moderate weight gain (5-10g/kg/day) check intake or check for infection
- Watch for secondary infection

D) Introducing Catch up Growth formula (F100)


- Gradual transition from F75 to F100 (usually over 48-72 hrs).
- Increase successive feed by 10 mls till some feeds remains uneaten.
- Modified porridge or complementary food can be used, provided they have
comparable energy and protein levels.
- Gradually wean to normal diet, unlimited frequent feeds, 150-220 kCal/kg/day.
- Offer protein at 4-6 g/kg/day.
- Continue breast feeding if child is breastfed.
Note: If child refuses F75/F100 and is too vigorous for forced RT feeding, then give normal diet. However must calculate
calories and protein (as above).

E) Discharge criteria
- Not oedematous.
- Gaining weight well.
- Afebrile.
- Has completed antibiotics.
- Aged ≥ 12 mths (*<12 mths: A Specialist opinion is required before discharge).

49
Infant Feeding
A) Breast-Feeding
Dr Koe Swee Lee MD(NUS), MMed(NUS), MRCP(Edinburgh), IBCLC(Queensland)
Prof. Dr. Lucy Lum Chai See, MBBS(UM), MRCP(UK)

Advantages:
Baby Mother
- Provide ideal nutrition for infants during 4-6 - Free of charge (saves medical expenses)
months of life - Promotes close attachment btw mother-child
- Easily digest, optimal temperature, less allergy - Natural contraception (lactational amenorrhoea)
- Reduce GI infections (developing country), - Not fully reliable but effectiveness increase with
Necrotising enterocolitis (preterm infants) time interval between children
- Improve cognitive development (dt presence of - Important in reducing birth rate in developing
polyunsaturated long chain fatty acids, takes part countries (family planning)
in myelination) - Reduce post-partum haemorrhage (PPH) during
- Foster maternal-infant bonding rooming-in, stimulates oxytocin production
- Reduce indicence of IDDM, obesity, IBD, STD, - Reduce risks of pre-menopausal breast cancer,
pneumonia, otitis media, meningitis osteoporosis
- Enhance visual acuity, IQ, speech development

Protective factors of Breastfeeding in baby


Immunological Humoral
- Secretory IgA (90% of breastmilk Ig)
- Mucosal protection against gut and respiratory infections
- bifidus factor
- Promotes growth of Lactobacillus bifidus
- Metabolises lactose > lactic acid > acetic acid
- Acidic environment (low pH) inhibit growth of GI pathogens
- Lysozyme (bacteriolytic enzyme)
- Lactoferrin
- Iron-binding protein, inhibits growth of E. Coli
- Interferon (antiviral agent)
Cellular
- Macrophages
- Phagocytic, synthesise lysozyme, lactoferrin, C3, C4
- Lympthocytes
- T lymphocytes (may transfer delayed hypersensitivity to infant)
- B lymphocytes (synthesise IgA)
Nutritional - Protein digestion made easier (casein: whey = 40: 60)
- Lipid quality (rich in oleic acid with palmitate in C2 position)
- Improves digestibility and fat absorption
- Hypoallogenic (reduce atopy, conflicting evidence)
- Breakmilk lipase (enhanced lipolysis)
- Calcium: Phosphorus = 2:1
- Prevents hypocalcaemic tetany, improves calcium absorption
- Higher iron content and bioavailability (40-50% absorption)
- Long-chain polyunsaturated fatty acids (retinal development)
- !-Lactalbumin (Increase lactose , Bactericidal, Antitumour activity)

50
Disadvantages:
Intake Unknown volume of milk intake (under or over-concentration)
Infections Transmission of CMV, hepatitis & HIV from infected mother
Breastmilk Jaundice Unconjugated hyperbilirubinaemia due to:
- Increased enterohepatic circulation (increased brush border B-
glucuronidase deconjugation activity and reabsorption)
- Pregnanediol in breastmilk inhibit glucuronyl transferase reducing
conjugation and reduce excretion of conjugated bilirubin.
- Mild, self-limiting (NOT an indication to stop breastfeeding)
Drug transmission Transmission of drugs from maternal blood (eg. anti-thyroid, cathartics,
anti-metabolites)
Nutrient Prolonged exclusively breastfeeding > 6 months of age, leading to poot
weight gain, nutritional deficiency (eg. rickets)
Vitamin K deficiency (insufficient vit K to prevent haemorrhagic disease
of newborn)
Contamination Environmental contaminants (eg. nicotine, alcohol, caffeine etc)
Less flexibility Other family members unable to take part unless expressed breastmilk
Emotion Emotional upset if unsuccessful

Guidelines on Breastfeeding:
- WHO recommends exclusive breastfeeding for 6 months then continue breastfeeding to 2
years and beyond with addition of complementary food (weaning).
- First step: Facilitate breastfeeding in first hour (latest by fourth hours)
- Baby takes 40-50 minutes to latch naturally on nipple
- Rooming-in provides skin-skin contact, keeps baby warm
- Receive colostrm (produced for first few days, low volume, more concentrated, higher protein
and immunoglobulin content as compared to mature mlik) -> Baby is rotected from flora
acquired from mother
- Second step: Feed frequently (1-2 hourly during day, 3 hourly during night)
- Third step: Feed properly
- Position (chest-to-chest contact with baby lies on side, direct mouth-to-nipple not opposite)
- Cradle position, Cross-cradle position
- Latching (infant latches on mother`s nipple and much of the areola, stimulate upper lip,
mouth wide opens)
- Practice
- Chin against breast makes deep suckling movement and swallowing to be heard
- Do not pull baby off breast while still feeding, feed till baby sleeps and let go
- Offer the breast again till baby is satisfied, feed 1 feed on 1 breast
- No limit in duration and frequency of breastfeeding, must satisfy baby`s suckling needs
- Colostrum
- Thick, yellowish milk secreted for first 5-7 days (small amount during first few days due to high
progestrogen which inhibits prolactin from stimulating milk production)
- Ideal nutrient and immunological substances Constituent Colostrum Mature
- Volume of colostrum: Remarks: /100ml Milk
Day 1: 50ml/day Lactose prevents Energy [K cal] 58.0 70.0
Day 2: 100ml/day hypoglycaemia, facilitates Lactose [g] 5.3 7.0
passage of meconium and Protein [g] 2.3 0.9
Day 3: 135ml/day
excretion of bilirubin Fat [g] 2.9 4.2

51
- Mother produces less breastmilk because of poor breastfeeding practice:
- Lack of information and family support
- Limited breastfeeds in frequency and duration
- Switch breastfeeding, Given bottle feeds and water with breastfeeding
- Baby given pacifiers or not given night breastfeeds
- Symptoms when baby has enough breast milk:
- Passing pale urine 5-6 times/day
- Passing yellow stools 3-8 times/day
- Baby is contented about 1 hour after a feed
- Baby puts on at least 20g/day
- Differences between:
Breastfeeding Jaundice Breastmilk Jaundice
- Suboptimal breastfeeding - Prolonged jaundice for 6-8 weeks
- Baby does not get enough breast milk and - increased brush border B-glucuronidase
calories deconjugation activity and reabsorption)
- Jaundice of starvation - Pregnanediol in breastmilk inhibit
- Reabsorption of unconjugates bilirubin glucuronyl transferase reducing
- Management: Correct breastfeed practice, conjugation and reduce excretion of
increase feeding frquency and duration conjugated bilirubin.
- Normal development
- Management: Continue breastfeeding
- Contraindications to breastfeeding:
- Mother is HIV positive
- Mother is being treated for cancer soon after delivery
- Mother is on radioactive drugs for any treatment or investigation
- Maternal conditions (acute infections, septicaemia, ecampsia, nephritis, profuse haemorrhage,
active TB, leprosy, typhoid fever, breast cancer, malaria, chronic poor nutrition, cardiac failure,
substance abuse, inverted nipples, fissuring or cracking of nipples, lactational mastitis)
- Infantile conditions (metabolic disease like galactossaemia, phenylketonuria)
- Non-contraindications to breastfeeding:
- Children is ill with respiratory infections or diarrhoea and is on medications
- Mother is ill with infections and other illnesses
- On other medications (most drugs are compatible with breastfeeding)

B) Formula Feeding
- WHO & MOH recommend formula feeding if the conditions are AFASS (Affordable, Feasible,
Acceptable, Sustainable, Safe)
- Unmodified formula milk (unsuitable for infancy feeding as it contains too much protein and
electrolyte but inadequate iron and vitamins)
- Modified formula milk (Casein: Whey ratio = 40: 60, similar to breastmilk which forms smaller
curd and provides similar amino acid profile)
- Raw milk (unsuitable for infants before 6 months, easily contaminated, form large milk curd,
difficult to digest)
- Pasteurised milk (may contain high bacterial count, should be boiled before consumption)
- Condensed milk (added with cane sugar, 60% carbohydrate, unsuitable for infants)
- Dried skim milk (high mineral and protein content, may cause severe dehydration, unsuitable
for infants)

52
C) Pasturised Cow`s Milk (eg. Dumex)
- Higher casein (Casein: Whey ratio = 63: 37), which is more difficult to digest
- Higher in Ca, Na, PO4 (increased renal solute load)
- Deficient in Vitamin A, C, D and iron

D) Goat`s milk
- Used in cow`s milk allergy, low in vitamin D, iron and folic acid
- Susceptible to megaloblastic anaemia, brucellosis (boiled before use)

D) Soya Formulae (eg. Nursoy, Isomil)


- Indications: Lactose intolerance after acute diarrhoea (short term), galactosemia (long term)
- Biological value of protein lower than that of milk protein, less essential and semi-essential
amino acids
- Nutritionally adequate (loss of vitamins, minerals and trace elements) and support normal
growth
- Have high aluminium and phytoestrogen content

Weaning
- Introduction of solid food which is ideally done between the age of 4 to 6 months.
- After 6 months of age, breast milk becomes nutritionally inadequate as a sole feed, leading to
deficiencies in energy(increased calorie demand), vitamins and iron
- Breastmilk still essential during weaning, encourage as long as possible.
- New food should be offered once a day in a small amount: 1-2 tablespoon(s)
- Use small spoon that fits infant`s mouth, anticipate `spitting out`
- Use same food for 1-2 week until infant is used to the food before introducing new food
- Avoid overzealous, infantile obesity
- Suitable foods: cereals, fruits, vegetabl, eggs, home-prepared food.
- Feeding difficulties during first year of life:
- Underfeeding: restless, hungry, failure to gain weight
- Overfeeding: regurgitation, vomiting, infantile and adult obesity
- Regurgitation and vomiting (common in first few months, usually self-limiting)
- Loose or diarrhoeal stools, Constipation(rare in breastfed infants)

Comparison of different infant milk:


Breastmilk Term formula Preterm Cow`s milk
formula
Energy (kcal/100ml) 70 65 80 67
Carbohydrate (g/100ml) 7.4 7.2 8.6 4.6
Protein (g/100ml) 1.1 1.5 2.0 3.4
Casein: Whey 40 : 60 63 : 37
Casein: lactalbumin 2:3 4:1
Fat (g/100ml) 4.2 3.6 4.4 3.9
Sodium (mmol/100ml) 6.4 6.4 14 23
Potassium (mmol/100ml) 15 14 19 40
Calcium (mmol/100ml) 8.5 10.8 18 30
Phosphate(mmol/100ml) 5 10.6 13 32

53
Malnutrition

- Categorised into short-term response of wasting (weight for height ratios) and long-term
response of stunting (height for age, sex ratio) [weight for age ratio cannot differentiate short or long term]

Causes of malnutrition in children:


Inadequate intake of food - Starvation*
- Poverty*
- Restrictive diets (parental, iatrogenic, self-inflicted, anorexia nervosa)
- Anorexia due to chronic illness
- Late weaning (>1 yrs) - resist solid food when get used to milk, iron-
deficiency anaemia
Malabsorption - Pancreatic disease (Cystic Fibrosis)
- Coeliac disease
- Show bowel syndrome (post-operative)
- Cow`s milk protein intolerance
Increased energy - Chronic infection (hookworm, parasitic, protozoa infections,
requirement HIV, malaria, TB)
- Malignancy
- Burns/ trauma
*Responsible for worldwide childhood death
**Most common dietary deficiencies are iron and vitamin D deficiency

Consequences of Severe Malnutrition:


- Impaired immunity, delayed wound healing
- Apathy and inactivity
- Impaired intellectual development/cognitive function
- Permanent bony deformities or stunted grotwth
- Developmental delay

Nutritional Assessment:
- Dietary history
- Food intake as recalled by parents or recorded ina diary over several days
- Food quantity, preparation, frequency, budget limitation
- Physical Examination
- Anthropometry
- Height (stunted growth in chronic malnutrition)
- Weight (reduced weight with normal height(wasting) indicates acute malnutrition)
- Mid-arm circumference (indication of skeletal muscle mass, <115mm: severe malnutrition)
- Triceps skin-fold thickness (measurement of subcutaneous fat stores)
- Physical signs (Refer pg.52)
- Investigations:
- Serum albumin (nutritional status, reduced in severe malnutrition)
- FBC (low Hb, lymphocyte count)
- Blood glucose
- Serum calcium, phosphate, vitamin D, potassium, magnesium
- Serum B12, folate, iron, ferritin; Schilling test - to differentiate causes of vit B12 deficiency
- Radiology (wrist X-ray)

54
Physical Signs of Nutritional Deficiency Disorders:

Protein-energy Malnutrition:
Marasmus Kwashiorkor
- Deficiency of both protein and calories, results in - Disproportionately low protein intake compared
non-oedematous malnutrition with calorie intake, oedematous malnutrition
- Decreased weight for age & sex ratio (<60% mean) - Near-normal weight for age & sex ratio (<80%)
- Appears loose, wrinkled skin, `old man` wizened, - Appears oedematous, hypoalbuminaemic, overall
decreased skin turgor `fatness`, moon face, lethargic, miserable, LOA
- Muscle atrophy and little subcutaneous fat - Marked muscle atrophy but spared subcutanous fat
(reduced mid-arm circumference, skinfold thickness)
- Thin, sparse, easily pull out hair, hair colour unusual - Thin, red hair and darkened skin (hyperpigmented
changes hyperkeratosis), erythematous macular rash
(pellagroid),`Flaky-paint` rash, angular cheilosis,
monilial stomatitis, fissures, ulcers), parotid gland
enlargement, hepatomegaly
- Hypothermia, bradycardia, hypotension (reduced - Precipitated by infections, secondary
metabolic rate) immunodeficiency

55
Mixed Maramus-Kwashiorkor
- Concurrent wasting and oedema with stunting
- Weight for age & sex ratio (<60%) + Oedema
- Features: dermatitis, neurological abnomalities, fatty liver

Management
- Nutritional rehabilitation should be initiated and advanced slowly to minimize complications:
- Enteral nutrition (Preferred whenever possible, via GI tract, nasogastic or gastostomy tube)
- Parenteral nutrition (Directly into circulation)
- Antibiotics or antiparasites if indicated
- Oral rehydration over IV fluid is recommended to avoid excessive fluid, solute load and
resultant heart/ renal failure.
- Calorie intake is increased till appropriate regrowth or catch-up growth is initiated.
- Refers to gaining weight > 50th percentile for age and may require ≥150% calories than well-
nourished child
- General rule of thumb for infants and children ≤3 years age: Provide 100-120 kcal/kg based on
ideal weight for height
- Complication: Refeeding Syndrome
- Characterized by fluid retention, hypophosphatemia, hypomagnesemia, hypokalemia.

Enteral Nutrition Parenteral Nutrition


- Used when digestive tract is functioning, - Used exlusively or as an adjunct to enteral
maintain gut function and safe feeds to maintain or enhance nutrition
- Feeds are given by gastrostomy or feeding - Provide nutritionally complete feed in an
tube in jejunum appropriate volume of IV fluid
- Given continuously overnight, allow child to - Short-term, delivered via peripherally sited
feed normally during the day cannula
- Gastrostomy is preferred in long-term as it - Long-term, delivered via CVP as it allows
avoids repeated replacement of nasogastric infusion of hyperosmolar solution, not
tubes require repeated resitting of cannula
- Complications: sepsis, blockage, problems of
vascular access on repeated line treatment,
liver disease.

Examples of chronic disease requiring supplemental feeding:


- Cystic fibrosis
- Congenital heart disease
- Cerebral palsy
- Chronic renal failure
- Malignancy
- Inflammatory bowel disease
- Anorexia nervosa

56
Micronutrients Deficiency

Overview:
Vitamin Clinical Condition in Deficiency Source
Vitamin A - Night blindness Liver, mlik, eggs, green
(Retinol) - Xerophthalmia and yellow vegetables,
- Bitot spots fruits
- Follicular hyperkeratosis, immune defects
Vitamin B1 - Beri-beri (polyneuropathy, calf tenderness, Liver, meat, milk, cereals,
(Thiamine) heart failure, oedema, opthalmoplegia) nuts, legumes
Vitamin B2 - Anorexia, mucositis Milk, cheese, liver, meat,
(Riboflavin) - Anaemia, cheilosis eggs, whole grains, green
- Nasolabial seborrhoea leafy vegetables
Vitamin B3 - Pellagra (photosensitivity, dermatitis, Meat, fish, liver, whole
(Niacin) dementia, diarrhoea, death) grains, green leafy
vegetables
Vitamin B9 - Megaloblastic anaemia Meat, fish, cheese, eggs
(Folate) - Neural tube defects
Vitamin B12 - Megaloblastic anaemia Meat, fish, cheese, eggs
(Cobolamin) - Peripheral neuropathy
- Subacute combined degeneration of spinal
cord (posterolateral dorsal column disease)
- Vitiligo
Ascorbic acid - Scurvy (irritability, purpura, bleeding gums, Citrus fruits, green
periosteal haemorrhage, aching bones) vegetables, cooking
destroys
Vitamin D - Rickets (reduced bone mineralisation) Fortified milk, cheese,
liver, sunlight
Vitamin E - Haemolysis in preterm infants Seeds, vegetables, germ
- Areflexia, ataxia, opthalmoplegia oils, grains
Vitamin K - Haemorrhagic disease of newborn Liver, green, vegetables,
- Elevated protein-induced vitamin K absence made by intestinal flora
(PIVKA)

Vitamin A Deficiency:
- Vitamin A is necessary for membrane stability and plays a role in vision, keratinisation,
cornification and placental development.
- Functions:
- Retinol is metabolised to form rhodopsin, first step in visual process
- Growth and differentiation of epithelium
- Complications:
- Xerophthalmia (Xerosis of conjunctiva and cornea, untreated leads to ulceration, necrosis,
keratomalacia, corneal scarring)
- Night blindness (impaired dark adaptation)
- Immunodeficiency (increased risk of infection esp measles, increased mortality risk in
developing nations)
*Hypervitaminosis A (headaches, pseudotumour cerebri, hepatotoxicity, teratogenity)
57
Vitamin D Deficiency:
- Most common form of vitamin deficiency, appears as Ricket in children and Osteomalacia in
post-pubertal adolescents.
- Functions:
- Enhanced intestinal absorption of calcium and phosphate via 1,25-(OH)2-D
- Direct anabolic effect on bone
- Inhibit PTH secretion via negative feedback of raised 1,25-(OH)2-D
- Causes of deficiency:
- Failure to achieve minimum daily nutritional requirement of vitamin D of 400IU especially in
infants who are breastfed for a protracted period (most common)
- Decreased sun exposure especially in infants with dark skin pigmentation, urban living
conditions and winter
- Inherited abnormalities of vitamin D metabolism or vitamin D receptor
- Mineral deficiency eg. X-linked hypophosphataemia
- Decreased activity of 1α-hydroxylase in chronic renal disease (renal osteodystrophy)
- Liver disease (impaired metabolism of vitamin D)
- Anticonvulsants eg. phenytoin (metabolises vitamin D)
- Prematurity
- Metabolic bone disease in the premature infant occurs if the milk used contains inadequate
calcium and phosphorus (1,25-(OH)2-D raised due to hypophosphataemia stimulus, but there
is osteopenia and inadequate minieralisation of growing bone)
- Increased phosphate excretion (familial hypophosphataemic rickets, vitD-dependent rickets -
type I or II (receptor defect), Fanconi syndrome)

Rickets
- Inadequate mineralisation of bone matrix (osteoid) of the growing bones due to vitamin D
deficiency.
- Demineralised bone is less rigid, bends and twists in an abnormal way
- Clinical features:
General - Misery, hypotonia, developmental delay, growth failure
- Dwarfism, pot belly, kyphosis, small pelvis, coxa vara
Head - Large anterior fontanelle with delayed closure (> 2 years)
- Craniotabes (ping-pong ball sensation on touching skull, thinning of
outer table of skull)
- Frontal bossing
- Late dentition with enamel defects
Chest - Rachitic rosary (enlargement of costochondral junctions)
- Harrison sulcus (horizontal depression/groove along the lower border of
the thorax corresponding to costal insertion of diaphragm)
- Pigeon chest
Skeletal - Thickened wrists and ankles (enlarged metaphyses)
- Bow legs (caused by weight bearing)
- Knock knees
- Greenstick fractures (long bones)
Metabolic - Hypocalcaemia (seizures, neuromuscular instability (tetany occurs when
serum Ca <7.5 mg/dl), apnoea, stridor

58
- Diagnosis:
History - Poor vitamin D intake
- Little exposure to direct UV sunlight
Blood - Serum calcium (low/normalise by 2` hyperPTH)
- Serum phosphate (low)
- Serum ALP (elevated)
- Serum PTH (elevated)
- Serum 1,25-(OH)2-D low/normal
- Serum 24,25-(OH)2-D undetectable
Radiology - Distal ulna and radius changes
- Distal widening, increased joint space
- Concave cupping and fraying
- Poorly dermacated ends
- Increased space between distal ends of radius and ulna
- Enlarged metacarpal bones
- Non-ossified metaphysis
- Cysts, subperiosteal erosions, fractures, Looser`s zones

- Management:
- Prevention by health education, exposure to sunlight, diet supplementation with minerals
and vitamin D
- Treatment of nutritional rickets with vitamin D3 (1,25-(OH)2-D) 5,000-10,000IU/day initially for
several weeks followed by provision of 400IU/day in the diet
- Biochemical and radiological monitoring may be required
- Monitor for excess chronic vitamin D symptoms (hypercalcaemia, muscle weakness, polyuria,
nephrocalcinosis)

(a)(b) Irregular mineralization and fraying of the provisional zones of


calcification at the distal ends of the radius and ulnar. The distal radius is
cupped. (c) Diffusely osteoporotic shafts with florid fraying, cupping and
splaying of the distal end of the femur and proximal ends of the tibia and
fibula. Note bowing of the distal shafts of the tibia and fibula. (d) Healing
after 6 months of treatment. Note recalcification of the metaphyses at the
end of the long bones


Rachitic rosary

59
Prematurity

Definition:
Premature infant < 37 weeks Period of Gestation (POG)
Low Birth Weight (LBW) < 2.5 kg at birth
Very Low Birth Weight (VLBW) < 1.5 kg at birth
Extremely Low Birth Weight (ELBW) < 1.0 kg at birth
Small for Gestational Age (SGA) < 10th centile of birth weight for age
Large for Gestational Age (LGA) > 90th centile of birth weight for age

Complications in Premature infants:


Temperature Thermal instability (thermoregularatory mechanism not fully developed
and low body fat)
Respiratory Respiratory Distress Syndrome (RDS)
Apnoea
Pneumothorax
Pulmonary haemorrhage
Bronchopulmonary dysplasia (BPD)
Cardiovascular Patent ductus arteriosus (PDA)
Persistent pulmonary hypertension of newborn (PPHN)
Neurological Apnoea, Hypoxic-ischaemic encephalopathy (HIE)
Intracranial haemorrhage
Periventricular leukomalacia
Lack of primitive reflexes (eg. suckling)
Gastrointestinal Intolerance of enteral feeding
Gastoesophageal Reflux Disease (GERD)
Necrotising enterocolitis (NEC)
Paralytic ileus
Neonatal jaundice
Urological Inability to concentrate urine
Inability to excrete acid load
Immunological Susceptibility to infections (immature immunity)
Septicaemia
Opthalmological Retinopathy of prematurity (may lead to blindness)
Metabolic Hypoglycaemia
Electrolyte imbalance (eg. hypocalcaemia, hyponatraemia, hyperkalemia,
metabolic acidosis)
Osteopenia of prematurity
Haematological Iron-deficiency anaemia
Physiological anaemia
Hypoprothrombinaemia
Surgical Inguinal hernia
Umbilical hernia
Others Neuro-developmental disability
Psychosocial problems

60
Management:

- Before and During Labour


- Prewarmed incubator and appropriate equipment for neonatal intensive care should always
be kept ready in the labour room or operating theatre.

- Adequate Resuscitation

- Transfer from Labour Room (LR) to NNU (Neonatal Unit)


- Use prewarmed transport incubator if available. If not the baby must be wiped dry and
wrapped in dry linen before transfer. For extremely low birth weight infant, from birth, the
infant should be wrapped up to the neck with polyethylene plastic wrap or food plastic bag to
prevent evaporative heat loss.
- If infant`s respiration is inadequate, keep the infant intubated with manual bag ventilation
with oxygen during the transfer.
- For those with mild respiratory distress, preferably initiate CPAP in labour room, and if
tolerated CPAP during transport. Use a pulse oxymeter where available.

- Admission Routine
- Ensure thermoneutral temperature for infant. Incubator/ radiant warmer is necessary for more
premature and ill infants.
- Ventilation in NICU is often necessary if ventilated during transfer. However, some infants take
longer to adapt to extrauterine life and may not require ventilation especially those with no
risk factors and given a full course of antenatal steroids. For the larger preterm infants above
1250 grams, review the required ventilation to maintain a satisfactory blood gas and consider
extubation if the ventilator requirements are low, patient has good tone and good
spontaneous respiration.
- Maintain SaO2 between 89-92% for ELBW; 90-94% for the larger preterm
- Head circumference (OFC), length measurements, bathing can be omitted.
- Quickly and accurately examine and weigh the infant.
- Assess the gestational age with Dubowitz or Ballard score when stable
- Monitor temp, HR, RR, BP and SaO2.

- Immediate Care for Symptomatic infants


- Investigations are necessary as indicated and include blood gases, blood glucose (dextrostix),
FBC with differential WBC and IT ratio (if possible), blood culture, CXR (symptoms present)
- Start on 10% dextrose drip
- Correct anaemia
- Correct hypotension (keep mean arterial pressure (MAP) > gestational age (GA) in wks). Ensure
hyperventilation is absent (cause hypotension). If the baby has good tone and active, observe
first as the BP may rise after first few hours of life towards a MAP reaching GA in weeks.
- Correct hypovolaemia: Give 10 ml/kg of Normal Saline over 20-30 mins, or packed cells if
anaemic. Avoid repeat fluid boluses unless there is volume loss.
- Start inotrope infusion if hypotension persists after volume correction.
- Start antibiotics after taking cultures (eg. Penicillin and Gentamycin).
- Start IV Aminophylline or caffeine in premature infants <32-34 weeks.
- Maintain SaO2 at 89-92% and PaO2 at 50-70 mmHg.

61
- General Measures for Premature infants
- Monitor vitals signs (colour, temperature, apex beat, respiratory rate). Look for signs of
respiratory distress (cyanosis, grunting, tachypnoea, nasal flaring, chest recessions, apnoea). In
VLBL and ill infants pulse oximetry and blood pressure monitoring are necessary.
- Check Blood Sugar
- Keep warm in incubator at thermoneutral temperature for age and birth weight. ELBW should
preferably have humidified environment at least for the first 3 days.
- Ensure adequate nutrition.
- Provide parental counselling and allow free parental access.
- Infection control: observe strict hand washing practices.
- Immunisation:
- Hep B vaccine at birth if infant stable and BW is >1.8 kg. Otherwise give before discharge.
- Ensure BCG vaccine is given on discharge.
- For long stayers other immunisation should generally follow the schedule according to
chronological rather than corrected age.
- Defer immunisation in the presence of acute illnesses.

- Supplements:
- At birth: IM Vitamin K (0.5 mg for BW<2.5 kg; 1 mg for BW ≥ 2.5 kg)
- Once on full feeding, give Infant Multivitamin drops 1 mls OD (continue till fully established
weaning diet).
- For preterm infants, use a formulation with Vit D 400 IU, and Folic acid 1 mg OD.
- Starting at ~4 weeks of life: Elemental Iron 2-3 mg/kg/day - to be continued for 3-4 months.

- Discharge
- Cranial Ultrasound for premature infants ≤32 weeks is recommended at:
- Within first week of life to look for intraventricular haemorrhage (IVH).
- Around day 28 to look for periventricular leucomalacia (PVL).
- As clinically indicated.
- Screening for Retinopathy of Prematurity (ROP) at 4-6 weeks of age is recommended for:
- All infants ≤32 weeks gestation at birth or birth weight <1.5 kg
- All preterms <36 weeks who received oxygen therapy depending on individual risk
- Infants are discharged once they are well, showing good weight gain, established oral
feeding and gestational age of at least 35 weeks.
NEONATOLOGY

62
Paediatrics Basic & Advanced Life Support (PBLS & PALS) [Source: Resus.org.uk]
SECTION A : PAEDIATRICS BASIC LIFE SUPPORT (PBLS)
Introduction:
Cardiorespiratory arrest occurs less frequently in children than in adults; thus, both healthcare
professionals and lay people are less likely to be involved in paediatric resuscitation. It is
therefore important to be familiar with the knowledge and skills required for paediatric BLS so
that the best care possible can be delivered in what is often a stressful situation.
Cardiopulmonary resuscitation (CPR) should start ASAP for optimum outcome. This should start
with the first person on scene, who is often a bystander (eg. a lay rescuer).
Majority of paediatric cardiorespiratory arrests are not caused by primary cardiac problems but
are secondary to other causes, mostly respiratory insufficiency, hence the order of delivering the
resuscitation sequence: Airway (A), Breathing (B) and Circulation (C).
Guideline Notes:
i) Recognition of cardiorespiratory arrest
- If a layperson or healthcare provider considers that there are no `signs of life`, CPR should be
started immediately.
- Pulse is neither reliable to imply effective/inadequate circulation, nor as CPR sole determinant
The presence or absence of `signs of life`, such as response to stimuli, normal breathing (rather
than abnormal gasps) or spontaneous movement must be looked for as part of the child`s
circulatory assessment.
- If healthcare provider does feel for a pulse in an unresponsive child, they must be certain that
one is present for them NOT to start CPR. In this situation, there are often other signs of life
present (Lay rescuers should not be taught to feel for a pulse as part of the assessment of need
for CPR). Decision to start CPR should take <10 seconds from starting the initial assessment of
the child`s circulatory status and if there is still doubt after that time, start CPR.
ii) Compression : Ventilation Ratios
- Rescuers who are unable or unwilling to provide breaths should be encouraged to perform at
least compression-only CPR. Child is far more likely to be harmed if the bystander does nothing.
- All providers should be encouraged to initiate CPR in children even if they haven't been taught
specific paediatric techniques. CPR should be started with the C:V ratio that is familiar and for
most, this will be 30:2.
- Paediatric modifications to adult CPR should be taught to those who care for children but are
unlikely to have to resuscitate them. Specific paediatric sequence incorporating the 15:2 ratio is
primarily intended for those who have the potential to resuscitate children as part of their role.
iii) Chest compression quality
- Uninterrupted, high quality chest compression is vital, with attention being paid to all
components of each chest compression including the rate, depth and allowing adequate time
for chest recoil to occur (approx 50% of the whole cycle should be the relaxation phase).
- In order to facilitate this for children, approximate dimensions of one-third compression depths
in infants & children are about 4 cm and 5 cm respectively.
- To maintain consistency with adult BLS guidelines, compression rate remains at 100-120 min
- Ideally chest compressions should be delivered on a firm surface otherwise depth of
compression may be difficult to achieve.

63
Paediatric basic life support algorithm (Healthcare professionals with a duty to respond):
Unresponsive → Shout for help → Open airway (to assess breathing)
Not breathing normally → 5 rescue breaths (then check for signs of life)
No signs of life → 15 chest compression → 2 rescue breaths, 15 chest compressions (if still fail)
Call resuscitation team (1 min CPR first, if alone)

PBLS Sequence:
For Healthcare professional teams,
1. Ensure the safety of rescuer and child
2. Check the child`s responsiveness:
- Gently stimulate the child and ask loudly, `Are you all right?`
3A. If the child responds by answering or moving:
- Leave the child in the position in which you find him (provided he is not in further danger)
- Check his condition and get help if needed
- Reassess him regularly
3B. If the child does not respond:
- Shout for help
- Turn the child onto his back and open the airway using head tilt and chin lift:
- Place your hand on his forehead and gently tilt his head back.
- With your fingertip(s) under the point of the child`s chin, lift the chin.
- Do not push on the soft tissues under the chin as this may block the airway.
- If you still have difficulty in opening the airway, try the jaw thrust method: place first two
fingers of each hand behind each side of child`s mandible (jaw bone) & push jaw forward.
- Have a low threshold for suspecting injury to the neck. If you suspect this, try to open the
airway using jaw thrust alone. If this is unsuccessful, add head tilt gradually until the airway is
open. Establishing an open airway takes priority over concerns about the cervical spine.
4. Keeping the airway open, look, listen, and feel for normal breathing by putting your face close
to the child`s face and looking along the chest:
- Look for chest movements
- Listen at the child`s nose and mouth for breath sounds
- Feel for air movement on your cheek
- In the first few minutes after cardiac arrest a child may be taking infrequent, noisy gasps. Do
not confuse this with normal breathing. Look, listen, and feel for no more than 10 seconds
before deciding - if you have any doubts whether breathing is normal, act as if it is not normal.
5A. If the child IS breathing normally:
- Turn the child onto his side into the recovery position (see below).
- Send or go for help : call the relevant emergency number. Only leave the child if no other way
of obtaining help is possible.
- Check for continued normal breathing.
5B. If the breathing is NOT normal or absent:
- Carefully remove any obvious airway obstruction.
- Give 5 initial rescue breaths.
- Although rescue breaths are described here, it is common in healthcare environments to have
access to bag- mask devices. Providers trained in their use should use them as soon as they
are available.
- While performing the rescue breaths note any gag or cough response to your action. These
responses, or absence, will form part of your assessment of `signs of life`, described below.
64
Rescue breaths for an infant:
- Ensure a neutral position of the head (as an infant`s head is usually flexed when supine, this
may require some extension) and apply chin lift.
- Take a breath and cover the mouth and nasal apertures of the infant with your mouth,
making sure you have a good seal. If the nose and mouth cannot both be covered in the
older infant, the rescuer may attempt to seal only the infant`s nose or mouth with his mouth
(if the nose is used, close the lips to prevent air escape).
- Blow steadily into the infant`s mouth and nose over 1 second sufficient to make the chest rise
visibly. This is the same time period as in adult practice.
- Maintain head position and chin lift, take your mouth away, and watch for his chest to fall as
air comes out.
- Take another breath and repeat this sequence four more times.
Rescue breaths for a child over 1 year:
- Ensure head tilt and chin lift.
- Pinch the soft part of his nose closed with the index finger and thumb of your hand on his
forehead.
- Open his mouth a little, but maintain the chin lift.
- Take a breath and place your lips around his mouth, making sure that you have a good seal.
- Blow steadily into his mouth over 1 second sufficient to make the chest rise visibly.
- Maintaining head tilt & chin lift, take your mouth away & watch for his chest to fall as air
comes out.
- Take another breath and repeat this sequence four more times. Identify effectiveness by
seeing that the child`s chest has risen and fallen in a similar fashion to the movement
produced by a normal breath.
For both infants and children, if you have difficulty achieving an effective breath, the airway may
be obstructed:
- Open child`s mouth & remove any visible obstruction. Do not perform a blind finger sweep.
- Ensure there is adequate head tilt and chin lift but also that the neck is not over extended.
- If head tilt and chin lift has not opened the airway, try the jaw thrust method.
- Make up to 5 attempts to achieve effective breaths. If unsuccessful, move to chest compression
6. Assess the circulation (signs of life):
Take no more than 10 seconds to:
- Look for signs of life. These include any movement, coughing, or normal breathing (not
abnormal gasps or infrequent, irregular breaths).
- If you check the pulse take no more than 10 seconds:
- In a child aged over 1 year : feel for the carotid pulse in the neck
- In an infant : feel for the brachial pulse on the inner aspect of the upper arm
- For both infants and children the femoral pulse in the groin (mid-way between the anterior
superior iliac spine and the symphysis pubis) can also be used.
7A. If confident that you can detect signs of a circulation within 10 seconds:
- Continue rescue breathing, if necessary, until the child starts breathing effectively on his own.
- Turn the child onto his side (into the recovery position) if he starts breathing effectively but
remains unconscious.
- Re-assess the child frequently.

65
7B. If there are no signs of life, unless you are CERTAIN that you can feel a definite pulse of >60
min-1 within 10 seconds:
- Start chest compressions.
- Combine rescue breathing and chest compressions.

For all children, compress the lower half of the sternum:


- To avoid compressing the upper abdomen, locate the xiphisternum by finding the angle
where lowest ribs join in the middle. Compress sternum one finger`s breadth above this.
- Compression should be sufficient to depress the sternum by at least one-third of the depth of
chest, which is approximately 4 cm for an infant and 5 cm for a child.
- Release the pressure completely, then repeat at a rate of 100-120 min-1.
- Allow the chest to return to its resting position before starting the next compression.
- After 15 compressions, tilt the head, lift the chin, and give two effective breaths.
- Continue compressions and breaths in a ratio of 15:2.
Chest compression in infants:
- Lone rescuer should compress the sternum with the tips of two fingers
- If there are two or more rescuers, use the encircling technique:
- Place both thumbs flat, side-by-side, on the lower half of the sternum (as above), with the
tips pointing towards the infant`s head.
- Spread the rest of both hands, with the fingers together, to encircle the lower part of the
infant`s rib cage with the tips of the fingers supporting infant`s back.
- Press down on the lower sternum with your two thumbs to depress it at least one-third of
the depth of the infant`s chest, ~4 cm.
Chest compression in children aged over 1 year:
- Place the heel of one hand over the lower half of the sternum (as above).
- Lift the fingers to ensure that pressure is not applied over the child`s ribs.
- Position yourself vertically above the victim`s chest and, with your arm straight, compress
sternum to depress it by at least one-third of the depth of the chest, approximately 5 cm.
In larger children, or for small rescuers, this may be achieved most easily by using both hands
with the fingers interlocked.

8. Continue resuscitation until:


- Child shows signs of life (normal breathing, cough, movement or definite pulse of >60 min-1)
- Further qualified help arrives.
- You become exhausted.

For rescuers who have been taught adult BLS, and have no specific knowledge of paediatric
resuscitation, should use the adult sequence. The following modifications to the adult
sequence will make it more suitable for use in children:
- Give 5 initial rescue breaths before starting chest compression.
- If you are on your own, perform CPR for 1 min before going for help.
- Compress the chest by at least one-third of its depth, approximately 4 cm for an infant and
approximately 5 cm for an older child. Use two fingers for an infant under 1 year; use one or
two hands for a child over 1 year to achieve an adequate depth of compression.
- Compression rate should be 100-120 min-1.

66
When to call for help:
- It is vital for rescuers to get help as quickly as possible when a child collapses:
- When >1 rescuer is available, ≥1 starts resuscitation while another goes for assistance
- If only one rescuer is present, undertake resuscitation for about 1 min before going for
assistance. To minimise interruptions in CPR, it may be possible to carry an infant or small child
whilst summoning help.
- Only exception to performing 1 min of CPR before going for help is in the unlikely event of a
child with a witnessed, sudden collapse when the rescuer is alone and primary cardiac arrest is
suspected. In this situation, a shockable rhythm is likely and the child may need defibrillation.
Seek help immediately if there is no one to go for you.
Recovery position
An unconscious child whose airway is clear and who is breathing normally should be turned
onto his side into the recovery position. There are several recovery positions; each has its
advocates. The important principles to be followed are:
- Place child in as near a true lateral position as possible to enable drainage of fluid from mouth
- Ensure the position is stable. In an infant, this may require the support of a small pillow or a
rolled-up blanket placed behind his back to maintain the position
- There should be no pressure on the chest that impairs breathing.
- It should be possible to turn the child onto his side and to return him back easily and safely,
taking into consideration the possibility of cervical spine injury.
- Ensure the airway is accessible and easily observed.
- Adult recovery position is suitable for use in children.
Explanatory Notes:
- Differences between adult and paediatric resuscitation are largely based on differing aetiology,
primary cardiac arrest more common in adults while secondary cardiac arrest more in children
- Onset of puberty, which is the physiological end of childhood, is the most logical landmark for
the upper age limit for use of paediatric guidelines
- Automated external defibrillators (AEDs)
- Capable of identifying arrhythmias accurately in children & extremely unlikely to advise a
shock inappropriately.
- Nevertheless, if there is any possibility that an AED may need to be used in children, the
purchaser should check that the performance of the particular model has been tested in
paediatric arrhythmias.
- Purpose-made paediatric pads (attenuate machine output : 50-75 J) are recommended for
children between 1- 8 years.
- Unmodified adult AED may be used if no such system or manually adjustable machine is
available
- For an infant in a shockable rhythm, risk: benefit ratio favours the use of an AED (preferably
with an attenuator) if a manually adjustable model is not available.

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SECTION B : PAEDIATRICS ADVANCED LIFE SUPPORT (PBLS)
Introduction:
Most paediatric arrests arise from decompensated respiratory/circulatory failure (predominantly
secondary cardiorespiratory arrests). Although in adulthood, primary arrests resulting from
arrhythmias are more common, many young adults have similar causes to children (eg. trauma,
drowning & poisoning), thus respiratory failure is also common in this population.
Cardiorespiratory arrest generally has a poor outcome in children hence the identification of the
seriously ill or injured child is an absolute priority. Directed interventions at the compensated or
decompensated stages of illness/injury can be life-saving and prevent progression to
cardiorespiratory arrest. Any unwell child or infant should be assessed in a systematic manner to
identify extent of any physiological disruption & interventions started to correct the situation.
Order of assessment & intervention for any seriously ill/injured child follows ABCDE principles:
Airway (for airway and cervical spine stabilisation for the injured child)
Breathing
Circulation (with haemorrhage control in the injured child)
Disability (level of consciousness and neurological status)
Exposure (full examination, respecting child`s dignity & ensuring body temp conservation)

Interventions are made at each step to identify abnormalities. Next step of the assessment is not
started until preceding abnormality has been treated & corrected if possible (exception if child
presenting with life-threatening haemorrhage after serious injury - circulatory interventions will
be made simultaneously with assessment, management of airway & breathing).
Paediatric rapid response team (RRT) or medical emergency team (MET) may reduce risk of
respiratory and/or cardiac arrest in hospitalised children. It should include at least one clinician
with paediatric expertise & one specialist nurse.

CPR Sequence: (Refer Algorithm pg. 74)


1. Establish basic life support (see PBLS section)
2. Oxygenate, ventilate, and start chest compression:
- Ensure a patent airway by using an airway manoeuvre described in PBLS section
- Provide ventilation initially by bag-mask, using high [inspired oxygen] as soon as available.
- Intubate the trachea only if this can be performed by an experienced operator with minimal
interruption to chest compressions. Tracheal intubation will both control airway & enable chest
compression to be given continuously, thus improving coronary perfusion pressure.
- Use a compression rate of 100-120 min-1
- If the child has been intubated and compressions are uninterrupted, ensure that ventilation is
adequate and use a slow ventilation rate of ~10-12 min-1
3. Attach a defibrillator or monitor:
- Assess and monitor the cardiac rhythm.
- If using a defibrillator, place one defibrillator pad or paddle on the chest wall just below the
right clavicle, and one in the mid-axillary line. Pads for children should be 8-12 cm in size, and
4.5 cm for infants. In infants and small children it may be best to apply the pads to the front
and back of the chest if they cannot be adequately separated in the standard positions.
- Defibrillator pads may be used to assess the rhythm, when in monitoring mode.

68
4. Assess rhythm and check for signs of life:
- Look for signs of life, which include responsiveness, coughing, spontaneous movements and
normal breathing.
- Assess the rhythm on the monitor:
- Non-shockable : asystole or pulseless electrical activity (PEA)
- Shockable : ventricular fibrillation (VT) or pulseless ventricular tachycardia (pVT)
5A. Non-shockable (asystole or PEA):
This is the more common finding in children.
Perform continuous CPR:
- Continue to ventilate with high-concentration oxygen.
- If ventilating with bag-mask give 15 chest compressions to 2 ventilations.
- Use a compression rate of 100-120 min-1.
- If the patient is intubated, chest compressions can be continuous as long as this does not interfere
with satisfactory ventilation.
- Once the child's trachea has been intubated and compressions are uninterrupted use a ventilation
rate of approximately 10-12 min-1. Note: Once there is return of spontaneous circulation (ROSC), the
ventilation rate should be 12-20 min-1. Measure end-tidal CO2 to monitor ventilation and ensure
correct tracheal tube placement.
Give adrenaline:
- If vascular access is established, give adrenaline 10 mcg kg-1 (0.1 mL kg-1 of 1/10,000 solution).
- If there is no circulatory access, obtain intraosseous (IO) access.
Continue CPR, only pausing briefly every 2 min to check for rhythm change.
- Give adrenaline 10 mcg kg-1 every 3-5 min (eg. every other loop), while continuing to maintain
effective chest compression and ventilation without interruption.
Consider and correct reversible causes (4Hs and 4Ts):
- Hypoxia
- Hypovolaemia
- Hyper/hypokalaemia, metabolic
- Hypothermia
- Thromboembolism (coronary or pulmonary)
- Tension pneumothorax
- Tamponade (cardiac)
- Toxic/therapeutic disturbance

5B. Shockable (VF/pVT)


Less common in children but may occur as a secondary event & is likely when there has been a
witnessed & sudden collapse. It is seen more often in the intensive care unit and cardiac ward.

Continue CPR until a defibrillator is available (same as 5A)


Defibrillate the heart:
- Charge the defibrillator while another rescuer continues chest compressions.
- Once the defibrillator is charged, pause the chest compressions, quickly ensure that all rescuers are
clear of the patient and then deliver the shock. This should be planned before stopping compressions.
- Give 1 shock of 4 J kg-1 if using a manual defibrillator.
- If using an AED for a child of <8 years, deliver a paediatric-attenuated adult shock energy.
- If using an AED for a child >8 years, use the adult shock energy.

69
Resume CPR:
- Without reassessing rhythm or pulse, resume CPR immediately, starting with chest compression.
- Consider and correct reversible causes (4Hs and 4Ts).
Continue CPR for 2 min, then pause briefly to check the monitor:
- If still VF/pVT, give a second shock (with same energy level & strategy for delivery as first shock)
Resume CPR:
- Without reassessing rhythm or feeling for a pulse, resume CPR immediately, starting with chest
compression.
Continue CPR for 2 min, then pause briefly to check the monitor:
- If still VF/pVT, give a third shock (with same energy level and strategy for delivery as previous shock).
Resume CPR:
- Without reassessing the rhythm or feeling for a pulse, resume CPR immediately, starting with
chest compression.
- Give adrenaline 10 mcg kg-1 and amiodarone 5 mg kg-1 after the third shock, once chest compressions
have resumed.
- Repeat adrenaline every alternate cycle (eg. every 3-5 min) until ROSC.
- Repeat amiodarone 5 mg kg-1 one further time, after fifth shock if still in a shockable rhythm.
Continue giving shocks every 2 min
- Continuing compressions during charging of defibrillator & minimising breaks in chest compression
as much as possible.
- After each 2 min of uninterrupted CPR, pause briefly to assess the rhythm:
- If still VF/pVT: Continue CPR with the shockable (VF/pVT) sequence.
- If asystole: Continue CPR & switch to the non-shockable (asystole or PEA) sequence as above.
- If organised electrical activity is seen, check for signs of life and a pulse:
- If there is ROSC, continue post-resuscitation care.
- If there is no pulse (or a pulse rate of <60 min-1), and there are no other signs of life, continue CPR
and continue as for the non-shockable sequence above.
- If defibrillation was successful but VF/pVT recurs, resume the CPR sequence and defibrillate. Give an
amiodarone bolus (unless two doses have already been given) & start a continuous drug infusion.

Important note:
Uninterrupted, high quality CPR is vital. Chest compression and ventilation should be interrupted only
for defibrillation. Chest compression is tiring for providers and the team leader should repeatedly
assess and feedback on the quality of the compressions. To prevent fatigue, change providers should
every two minutes. This will mean that the team can deliver effective high quality CPR so improving
the chances of survival.

Explanatory Notes:
Tracheal tubes - Studies show no greater risk of complications for children <8 years when cuffed,
rather than uncuffed, tracheal tubes are used in OT & ICU.
- Cuffed tracheal tubes are as safe as uncuffed tubes for infants (except neonates) &
children if rescuers use the correct tube size, cuff inflation pressure & verify tube
position. The use of cuffed tubes increases the chance of selecting the correct size at
first attempt. Under certain circumstances (eg. poor lung compliance, high airway
resistance, and facial burns) cuffed tracheal tubes may be preferable.
Alternative - Bag-mask ventilation remains first line method for achieving airway control &
airways ventilation in children
- Laryngeal mask airway (LMA) is an acceptable airway device for providers trained in
its use. It is particularly helpful in airway obstruction caused by supraglottic airway

70
abnormalities or if bag-mask ventilation is not possible.
- Other supraglottic airways (SGA) (eg. i-gel) which have been successful in children`s
anaesthesia may also be useful, but there are few data on the use of these devices in
paediatric emergencies. Supraglottic airways do not totally protect the airway from
aspiration of secretions, blood or stomach contents, and therefore close observation
is required as their use is associated with a higher incidence of complications in
small children compared with older children or adults.
Capnography - Monitoring end-tidal CO2 with waveform capnography reliably confirms tracheal
tube placement in a child weighing more than 2 kg with a perfusing rhythm and
must be used after intubation and during transport of an intubated child. The
presence of a capnographic waveform for >4 ventilated breaths indicates that tube
is in tracheobronchial tree, both in presence of a perfusing rhythm and during CPR.
- It does not rule out intubation of a bronchus. The absence of exhaled CO2 during
CPR does not guarantee tube misplacement because a low or absent end-tidal CO2
may reflect low or absent pulmonary blood flow.
- Povides information on the efficiency of chest compressions and a sudden rise in the
end-tidal CO2 can be an early indication of ROSC. Try to improve chest compression
quality if the end-tidal CO2 remains below 2 kPa as this may indicate low cardiac
output and low pulmonary blood flow
- Be careful when interpreting end- tidal CO2 values after giving adrenaline or other
vasoconstrictor drugs when there may be a transient decrease in end-tidal CO2, or
after the use of sodium bicarbonate when there may be a transient increase in the
end-tidal values. Current evidence does not support the use of a threshold end-tidal
CO2 value as an indicator for stopping the resuscitation attempt.

Drugs & Fluids used in CPR:


Adrenaline - Endogenous catecholamine with potent α, β1, β2-adrenergic actions
- Induces vasoconstriction, increases coronary, cerebral perfusion pressure &
enhances myocardial contractility
- Thought to stimulate spontaneous contractions & increases intensity of VF so
↑likelihood of successful defibrillation
- Recommended IV/IO dose : 10 micrograms kg-1. Subsequent doses of adrenaline are
given every 3-5 min. Do not use higher doses of intravascular adrenaline in children
because this may worsen outcome.
Amiodarone - Membrane-stabilising anti-arrhythmic drug, ↑duration of action potential &
refractory period in atrial and ventricular myocardium. Atrioventricular conduction is
also slowed and a similar effect occurs in accessory pathways.
- Mild negative inotropic action. Hypotension that occurs with IV amiodarone is
related to the rate of delivery and is due more to the solvent (Polysorbate 80 and
benzyl alcohol), which causes histamine release, than drug itself.
- In treatment of shockable rhythms, give an initial IV bolus dose of amiodarone 5 mg
kg-1 after third defibrillation. Repeat the dose after fifth shock if still in VF/pVT. If
defibrillation was successful but VF/pVT recurs, amiodarone can be repeated (unless
two doses have already been given) and a continuous infusion started.
- Can cause thrombophlebitis when injected into a peripheral vein and, ideally, should
be delivered via a central vein. If central venous access is unavailable (likely at the
time of cardiac arrest) and so it has to be given peripherally, flush it liberally with
0.9% sodium chloride or 5% glucose.
Atropine - Effective in increasing heart rate when bradycardia is caused by excessive vagal tone
(eg. after insertion of nasogastric tube). Dose is 20 mcg kg-1.
- No evidence that atropine has any benefit in asphyxial bradycardia or asystole and
its routine use has been removed from the ALS algorithms.
71
Magnesium - Major intracellular cation and serves as a cofactor in many enzymatic reactions.
- Indicated in children with documented hypomagnesaemia or with polymorphic VT
(torsade de pointes), regardless of cause.
Calcium - Vital role in the cellular mechanisms underlying myocardial contraction.
- However, high plasma concentrations may be harmful to ischaemic myocardium or
impair cerebral recovery.
- Given only when specifically indicated (eg. in hyperkalaemia, hypocalcaemia and in
overdose of calcium-channel-blocking drugs).
Sodium - Cardiorespiratory arrest results in combined respiratory and metabolic acidosis,
bicarbonate caused by cessation of pulmonary gas exchange & development of anaerobic cellular
metabolism respectively.
- Best treatment for acidaemia in cardiac arrest is a combination of effective chest
compression & ventilation (high quality CPR).
- Routine use of sodium bicarbonate in CPR is not recommended
- May be considered in prolonged arrests, specific role in hyperkalaemia &
arrhythmias associated with tricyclic antidepressant overdose.
- Administration of Na2CO3 generates CO2 (diffuses rapidly into the cells, exacerbating
intracellular acidosis if it is not rapidly cleared via the lungs, side effects include:
- Negative inotropic effect on an ischaemic myocardium.
- Presents a large, osmotically active, Na load to compromised circulation & brain.
- Produces a left shift in O2 dissociation curve, inhibiting release of O2 to tissues.
Fluids - Hypovolaemia is a potentially reversible cause of cardiac arrest. Give IV or IO fluids
rapidly (20 mL kg-1 boluses)
- Use sotonic saline solutions for initial volume resuscitation
- Do not use dextrose-based solutions for volume replacement (redistributed rapidly
away from ICF causing hyponatraemia & hyperglycaemia, which may worsen
neurological outcome)

Post-Resuscitation Care:
Oxygen - Room air is recommended for initial resuscitation of newborn
- 100% oxygen should be used for initial resuscitation for older child
- After ROSC, titrate the inspired oxygen, using pulse oximetry, to achieve an oxygen
saturation of 94-98%.
- In situations where dissolved oxygen important in oxygen transport eg. smoke
inhalation (CO poisoning) & severe anaemia, maintain a high inspired oxygen (FiO2).
Carbon - Controlled ventilation for those not recover immediately from ROSC (may help
dioxide prevent further secondary brain injury)
- Usual target range for PaCO2 in this setting is 4.5-5.0 kPa, but target value should be
towards anticipated value for the individual patient as `normal value` for a child with
a chronic respiratory disorder may exceed the quoted ranges based on children
without adaptive physiology.
IV fluids and - Following ROSC, use of fluids or inotropes to avoid hypotension is recommended to
inotropes ensure dequate tissue perfusion.
Extracorporeal - For rescue and post-ROSC, may benefit to those with cardiac origins of arrest &
membrane where it can be instituted rapidly.
oxygenation
(ECMO)
Prognostic - No single factor is sufficiently reliable, factors should consider include circumstances
factors for of the arrest, initial rhythm, duration of resuscitation and other features such as
resuscitation presence of hypothermia and severe metabolic derangement
outcomes - Comatose children with ROSC receiving mechanical ventilation who fulfill

72
neurological criteria for death, or in whom withdrawal of life-sustaining treatments is
planned should be considered as potential organ donors
Therapeutic - Child who has ROSC, but remains comatose after cardiorespiratory arrest, may
hypothermia benefit either from being cooled to a core temperature of 32-34`C (TH) or having
their core temperature actively maintained at 36.8`C for at least 24 h post arrest.
- Do not actively rewarm a successfully resuscitated child with hypothermia unless the
core temperature is below 32`C. Following a period of mild hypothermia, rewarm the
child slowly at 0.25-0.5`C h-1
Blood glucose - Both hyperglycaemia and hypoglycaemia are associated with poor outcome after
control cardiorespiratory arrest
- Closely monitor plasma glucose concentrations, do not give glucose-containing
fluids during CPR except for treatment of hypoglycaemia.

Parental Presence:
- Reports show that being at the side of the child is comforting to parents or carers and helps
them to gain a realistic view of attempted resuscitation and death.
- Bereaved families who have been present in the resuscitation room show less anxiety and
depression several months after the death.
- Encourage healthcare providers` professional behaviour & facilitate their understanding of the
child in the context of his/her family.
- A dedicated staff member should be present with the parents at all times to explain process in
an empathetic and sympathetic manner. They can also ensure that the parents do not interfere
with the resuscitation process or distract the resuscitation team. If the presence of the parents
is impeding the progress of the resuscitation, they should be gently asked to leave. When
appropriate, physical contact with the child should be allowed.
- Resuscitation team leader should decide when to stop the resuscitation; this should be
expressed with sensitivity and understanding. After the event, debriefing of the team should be
conducted, to express any concerns and to allow the team to reflect on their clinical practice in
a supportive environment.

73
Algorithm for Paediatrics Advanced Life Support (PALS):

74
PART III

NEUROLOGY
Down`s Syndrome (Trisomy 21)

Introduction:
- Most common autosomal trisomy, most common genetic cause of severe learning difficulties
and the development of complication.
Incidence of Down syndrome
Epidemiology: Maternal Age-Specific Risk for Trisomy
- Incidence is about 1:650 live births 21 at Livebirth (Overall Incidence: 1 in
- BUT individual incidence dependent on maternal 800 -1000 newborns)
age Age (years) Incidence
20 1 : 1500
30 1 : 900
35 1 : 350
40 1 : 100
41 1 : 70
42 1 : 55
43 1 : 40
44 1 : 30
45 1 : 25
TRISOMY 21
50 1 : 10
- However, most of DS babies are born to younger mothers because proportionately they have
more babies
- > 85% will survive to 1 year old; at least 50% affected individual live longer than 50 years old
- Risk factors : Increased maternal age and Family history (recurrence)

Cytogenetics (Inheritance):
Non-disjunction - Karyotype: 47, XY + 21
(95%) - Mostly from error during meiosis
- Paired chromosomes 21 failed to separate à 1 gamete with 2
chormosomes 21 and 1 gamate has none
- Fertilization of gamete with 2 chr 21 à trisomy 21
- Parental chromosome do not need to be examined
- Incidence rises with increased maternal age BUT not paternal
- Only 5 % are paternally derived
- Risk of recurrence of DS when have one child with trisomy 21
- 1 in 200 (<35 years old)
- 1 in 100 (>35 years old)
Translocation (4%) - Karyotype: 46, XY, -14, +t (14q21q)
- Results from an unbalanced Robertsonian translocation
- Usually extra chr21 translocated onto chr14, more rarely 15, 22 & 21.
- Affected child has 46 chromosomes, BUT 3 copies of chr21 material
- Parental chromosome analysis is essential due to parent translocation
carrier
- Risk of recurrence with one DS baby
- 10-15% recurrence risk if mother is carrier and 2.5% if father is carrier
- 100% if parent has the 21:21 translocation (very rare)
- <1% if neither parent has a translocation
75
Mosaicism (1%) - Karyotype: 47, XY + 21/46, XY
- Result from non-disjuction during mitosis after fertilisation
- Some cells are normal and some with trisomy 21
- Milder phenotype of DS

Clinical Features:

Single palmar crease is


seen with short phalanges
and matacarpals,
hypoplasia of mid-phalanx
of fifth finger with
clinodactyly.

Newborn
Facial appearance - Round face & short neck
- Flat occiput (brachycephaly & third fontanelle)
- Hypertelorism (abnormal ratio btw interpupillary distance and distance btw
lateral canthus
Brushfield spots
- Bilateral upward slanting of eyes Small, white, grayish
- Brushfield spots in iris or brown spots on the
- Congenital cataract, squint & glaucoma periphery of the iris in
the human eye due to
- Epicanthic folds aggregation of
- Flat nasal bridge connective tissue, a
- Protruding tongue normal iris element.

- Low set ears (ear lobe less than 1/3 below imaginary intercanthal line)
Upper and lower - Single palmar crease (simian crease)
limbs - Clinodactyly (incurved 5th finger)
- Short, stubby fingers
- Hypotonia
- Sandal gap between big toe and second toe
CVS Congenital heart defects
- AVSD(most common), VSD, PDA, ASD primum & Fallot`s tetralogy
GIT - Feeding problem
- Duodenal atresia
- Pyloric stenosis
- Tracheoesophageal fistula

76
- Hirschsprung disease
- Anorectal malformation
CNS - Congenital cataracts
- Glaucoma
Endocrine - Hypothyroidism
- Hypogonadism
Musculoskeletal - Congenital dislocation of the hips

Infant & childhood


General - Severe learning difficulties
- Mild to moderate mental retardation (mean IQ: 25-75)
- Delayed developmetal milestones
- Small stature (modified centile charts available)
- Feeding problems
CNS - Hearing impairment
- Secretory otitis media or sensorineural deafness
- Visual impairment
- Myopia (70 %), Squint, Nystagmus, Glaucoma
- Epilepsy (10%)
Respiratory - Recurrent respiratory infections (eg. URTI)
- Especially those with underlying congenital heart disease
- Upper airway obstruction
- Due to hypertrophy of tonsils & adenoids may lead to sleep apnoea and cor
pulmonale
GIT - Coeliac disease
Haematological - Transient Abnormal Myelopoiesis (TAM)
- Leukemia(AML when <2 yrs old, ALL when >3 yrs old)
Endocrine - Hypothyroidism
- Hypogonadism
- Diabetes Mellitus Type 1 (2 %)
Musculoskelatal - Atlanto-axial instability (rare)

* Walking, language & self-care are usually attained BUT independence is rare.
Adolescent and Adulthood
Puberty - Girls menarche only slightly delayed (fertility presumed)
- Boys are usually infertile due to low testosterone level
Others - Increased risk of Dementia/Alzheimer disease in adult life
- Shorter life expectancy

Diagnosis:
Antenatal Ultrasound - Nuchal fold thickness >3mm
(At 10-14th week)
- Double bubble sign (dilatation of
proximal duodenum & stomach)
Amniocentesis - Karyotyping: Trisomy 21
- At early 2nd trimester (16-18 weeks) - FISH
Chorionic villous sampling - Triple assessment
- After 18th week - ↓ AFP
- ↓ Oestradiol
- ↑ HCG
Newborn Blood sampling - Karyotyping & FISH
77
Routine blood test:
The blood should be screened for the following:
- Full blood count (FBC)
- C-reactive protein or viscosity
- Urea and electrolytes (Kidney function)
- Liver function Tests
- Thyroid function tests
- Random glucose and glycosylated haemoglobin (HgbA1c)
- Lithium and anti-epilepsy drug (AED) levels: check level before morning dose (`trough level`)
- Calcium and vitamin D levels if on AED, poor sun exposure or from a black or ethnic minority
- FSH in women who have not had a period for 6 months
- Consider prostate specific antigen (PSA) in men over 50 years

Management:
The following information and explanation should be conveyed before discharge from hospital:
- Information on Down Syndrome
- Short and long term implications
- Counseling (to deal with feeling of disappointments, anger and guilt)
- Contact with local parent support group
- Every child with down syndrome should have access to an Early Intervention Programme as
soon as possible
- Advice on potential recurrence risk and contraception until chromosomal diagnosis is available

Examination looking for Complications:


Growth
- Appropriate growth monitoring is essential. Those who are excessively short or underweight may have
additional pathology that may requires Ix and Rx
- Down`s syndrome specific growth charts provide essential reference values. The possibility of additional
pathology should be considered for those feeling in the lower centiles who do not have congenital
heart disease
- Overweight/ Obesity is not inevitable and should always be thoroughly assessed
Hearing problems
- Hearing assessment (6-10 months) include auditory thresholds, impedance tests & otoscopy
- Aim to establish whether there is permanent hearing loss by 10 months and instigate intervention
where nessasary.
Thyroid gland
- Baseline T4/TSH at birth or by 1-2 weeks of life
Cervical Spine Instability
- People with Down Syndrome have small risk for major neurological damage caused by cervical
spine instability
- While the need for Cervial spine Xrays is still debated, the American Academy of Peadiatrics
recommends for radiographs to be taken at 3 to 5 years old and repeated every 10 years. These studies
are more important for children who may participate in contact sports and are clearly indicated in those
who are symptomatic.
- Lateral cervical radiographs in the neutral, flexed and extended positions should be taken. The space
between the posterior segment of the anterior arch of C1 and anterior of the odontoid process of C2
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should be measured. Measurements of less than 5 mm are normal; 5 -7 mm indicated instability; >7mm
is grossly abnormal. The cervical canal width should also be measured.
- Children with Down Syndrome should not be barred from taking part in sporting activities
- Clinical symptoms: often mild, are currently the most useful predictors of future risk and merit urgent
cervical spine X-rays and specific referral
- Symptoms of spinal cord compression may include neck pain, unusual posturing of the head and neck
(torticollis), change in gait, loss of upper body strength, abnormal nerurological reflexes, and change in
bowel/bladder functioning
Orthopaedic problems
- Include developmental dysplasia of hip, acquired hip dislocation (related to ligamentous laxity), chronic
patellar dislocation, pes planus, ankle pronation, scoliosis, degenerative joint disease
CVS
- The cardiac status of every child must be established by age of 6 weeks by neonatal peadiatric
examination and ECHO
- Even with ECHO, an occasional lesion is missed. Thus, constant clinical vigilance is essential.
Opthalmological disorders
- Besides standard visual screening, all DS children should be assessed by a paediatric opthalmologist by
6-12 months of age, and then yearly.
OSA
- Major contributor to pulmonary hypertension and development of Eisenmnger`s syndrome in children
with DS and cyanotic CHD. ENT referral for tonsillectomy and adenoidectmy is appropriate.
Obesity (>120% ideal body weight)
- Less active, prefer indoor activites, lower BMR. Reduce calorie intake, increased exercise, weight-bearing

Follow-up:
At 6 weeks old 1. Review chromosomal results and provide nondirective counseling for
next pregnancy
2. Review T4/TSH results
3. Cardiac assessment
4. Confirm involvement in parent support group and EIP
5. Discuss parents` concerns
First year 1. Developmental assessment
(Every 3 months 2. Growth
for 12 months) 3. Hearing assessment at 6 to 10 months
4. Visual assessment for squint
5. Fill in forms for registration with welfare department
1-6 years old 1. Regular development assessment
(Once yearly) 2. Annual hearing and visual assessment
3. Annual thyroid function test
4. Begin Dental checks at 2 years old and continue 6 monthly thereafter
5. Check on EIP. Encourage entry into normal kindergarden
6. Plan school by age of 5
7-12 years old 1. Check on school performance and placement
(Once to twice 2. Dental checks 6 monthly
yearly) 3. Annual Hearing, Visual, Thyroid function test
Adolescent 1. Discuss sexuality and employment
79
Recommendations for Medical Surveillance for children with Down Syndrome
Birth-6 weeks 6-10 12 months 18 mths-2.5 yrs 3-3.5 yrs 4-4.5 yrs
months
Thyroid tests T4, TSH T4, TSH, T4, TSH,
antibodies antibodies
Growth Length, weight & head circumference checked Length, weight & head circumference checked at least
monitoring regularly & plotted on Down`s syndrome annually & plotted on Down`s syndrome growth charts
growth charts
Eye Visual behaviour. Check for congenital cataract Orthoptic, Visual acuity,
examination refraction,opthalmic refraction, opthalmic
examination examination
Hearing Neonatal Full audiological review (hearing, impedence, otoscopy) by 6-10 months and then
check screening annually.
Cardiology, Echocardiogram Dental assessment
other advice 0-6 weeks
Age 5 to 19 years Footnote:
Paediatric review Annually 1, Asymptomatic patients with mildly raised TSH (<10mu/l)
Hearing 2 yearly audiological review but normal T4 does not need treatment but test more
Vision/ Orthoptic check 2 yearly frequently for uncompensated hypothyroidism.
Thyroid blood test At age 5 years, then 2 yearly 2, Down syndrome centile charts at www.growthcharts.
School performance Check performance & placement Consider weight for length charts of typically developing
Sexuality & employment Discuss when appropriate, in children for weight assessment. If BMI > 98th centile or
adolescence underweigh, refer for nutritional assessment and guidance.
Note: The above table are suggested ages. Check at any other Re-check thyroid function if accelerated weight gain.
time if parental or other concerns. Perform DV during each 3, Performed by optometrist/ophthalmologist.
visit.
Adapted from Down Syndrome Medical Interest Group (DSMIG) guidelines.

Down Syndrome Long Case (Template)


1) History
- Presenting complaint
- Reason for current admission.
- HOPI
- SOCRATES about presenting complaint(s), TRO other differential diagnosis
- History for Down syndrome
Diagnosis - When made?
- Prenatal (increased nuchal fold thickness, maternal serum screening
- Birth
- Age in days)
- Where
- Problems/symptoms at birth/diagnosis:
- CVS: cyanosis, tachypnoea, poor feeding
- GIT: vomiting (duodenal atresia), delay in meconium passage
- Haemato: transient myeloproliferative disorder
- Vison & hearing aspects
- Who gave the diagnosis,
- Initial reaction to the diagnosis
- Initial investigations carried out (karyotype, full blood examination, CXR,
electrocardiography, echocardiography, angiography, abdominal X-ray, USS,
brainstem auditory evoked response, ophthalmological assessment)
- Genetic counselling given.
Initial treatment Surgical, any complications from surgery
- CVS: correction of atrioventricular canal
- GIT: correction of duodenal atresia; staged reduction of omphalocoele
Pharmacological (eg. diuretics) & side effects thereof.

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- Past-Medical & Surgical History
Past-medical - Indications for, and number of, previous hospital admissions
condition - Pattern and timing of change in condition
- CVS aspects: when cyanosis or heart failure developed, when and how it was
controlled
- GIT aspects: when operative procedures were undertaken, duration of
hospitalisation, how long until feeding was established). Episodes of
infection.
- Other disease complications
- Development of hypothyroidism, coeliac disease, obstructive sleep apnoea
(OSA), seizures, leukaemia
Past-medical or - CVS: Past surgery, complications, plans for further operative procedures. Past
surgical interventional catheter procedures. Medications, past & present, side effects of
intervention these, monitoring levels, treatment plans for the future. Antibiotic prophylaxis
for dental procedures, maintenance of dental hygiene. Compliance with
treatment. Any identification bracelet. Instructions for air travel and high
altitude. Any recent investigations monitoring treatment. Any recent changes
in treatment regimen, and indications for these.
- GIT: Past surgery, complications thereof, plans for further operative
procedures. Compliance with treatment (eg. following diet for coeliac disease).
Any recent investigations monitoring treatment. Any recent changes in
treatment regimen, and indications for these.
- Hearing and vision: past ear, nose and throat surgical intervention, hearing aid
placement, ophthalmological intervention, glasses.
- OSA: Past adenotonsillectomy, nasal mask continuous positive airway pressure
(CPAP).
- Treatments for other conditions: hypothyroidism, atlantoaxial subluxation,
seizures, leukaemia, arthritis, diabetes mellitus.

- Current Functional Status


Current state - CVS disease
of health Fatigue, shortness of breath, cough, sweating, poorfeeding, recurrent chest
infections; symptoms suggesting arrhythmias, such as syncope, alteration of
Note any of consciousness, dizziness, palpitations, `funny feeling` in the chest, chest pain)
the following - GIT disease
symptoms: Nausea, vomiting, change in bowel habit
- Recurrent infection (how often, what sites [usually upper or lower respiratory
tract], treatment required, any prophylactic antibiotics)
- Hearing impairment (compliance/problems with hearing aids, impacted
cerumen, ventilation tubes for chronic otitis media)
- Visual impairment (development of refractive disorders, keratoconus, corneal
opacities, cataracts).
- Weight concerns (obesity, non-compliance with diet, exercise or sign of
hypothyroidism)
- OSA symptoms (snoring, restless sleep, daytime somnolence)
- Skin problems
- Children: Seborrhoeic dermatitis, palmar/plantar hyperkeratosis, xerosis
- Adolescents: Folliculitis (esp back, buttocks, thighs, perigenital area), fungal
infections (skin and nails), atopic dermatitis
- Oral health
Level of oral hygiene, dental caries, peridontal disease, bruxism (stereotyped

81
orofacial movements with teeth grinding), intervention for malocclusion, non-
compliance with dental recommendations).
- Respiratory problems (recurrent pneumonia due to silent aspiration)
- Orthopaedic issues
- Limping can be due to atlantoaxial subluxation, acetabular dysplasia with
subluxing hips [not more common in DS, but may appear later], slipped femoral
epiphysis, arthritis or leukaemia
- Foot problems (hallux valgus, hammer toe deformities, plantar fasciitis, pedal
arthritis)
- Joint problems (polyarticular onset juvenile arthritis-like arthropathy)
- Diabetes mellitus (increased drinking or eating, weight loss, lethargy)
- Hypothyroidism (dry skin, cold intolerance, lethargy)
- Haematological neoplasia
Acute lymphoblastic leukaemia (ALL) or acute non-lymphoblastic leukaemia
(ANLL) occur 10-15x more frequently in DS, with usual symptoms of pallor,
bruising, fever, hepatosplenomegaly and lymphadenopathy
- Reproductive issues in adolescents
Difficulties with menstrual hygiene, use of oral contraceptives, Depo-provera,
presentation of premenstrual syndrome (PMS) with temper tantrums, autistic
behaviour episodes, seizures, sex education, desire to reproduce
- Neurological issues
Seizures (more frequent than general population, but less than other causes of
intellectual impairment), strokes (due to cyanotic CHD, or moyamoya disease)
Current state Ask about possible co-morbid psychiatric/behavioural issues:
of behaviour - Symptoms of ADHD (inattention, hyperactivity, impulsivity); any treatment for
these.
- Symptoms of ASD (impaired social interaction, impaired communication,
behaviour patterns including preferring own company, tendency to be loner, `in
their own world`), most problematic behaviours at present (eg. rituals, anxiety,
aggression, self-injury); any treatment for these.
- Other behavioural concerns: depression, conduct disorder, oppositional defiant
disorder, aggressive behaviour; any treatment for these.
- Impact of these co-morbid issues (on family, educational facility [eg. special
school], therapists, carers)

- Paediatrics history
Birth history Relevant antenatal, intrapartum & post-natal history, cord blood screening
Immunisation Any delays, local doctor`s attitudes, parents` understanding of importance of
immunisation.
Developmental Any developmental delay
Dietary Breastfeeding, weaning, feeding difficulty, food history

- Social history
Impact on Level of functioning in activities of daily living (ADLs), schooling (type of school,
child level of support from education department, therapists, academic performance,
teachers` attitudes, peer attitudes, teasing, amount of school missed and whether
schooling is appropriate
Impact on Effect of family`s financial burden, whether siblings feel comfortable to bring
siblings friends home, whether siblings miss out on parental time, plans for siblings to act
as guardians in future.

82
Impact on Financial situation, financial burden of disease so far, government allowances
parent being received, marriage/partnership stability, restrictions on social life, plans for
further children,genetic counselling, availability of prenatal diagnosis,contingency
plans for child`s future, guardianship and power of attorney issues
Social support Social worker, contact with DS parent support groups, any available respite.
Parents` degree of understanding regarding health supervision issues in DS.
Access to Access to local doctor, paediatrician, neurodevelopmental clinic, various
health subspecialty clinics attended (where, how often), other clinics attended,alternative
practitioner (e.g. homeopathy) involvement.

- Summary (include PC, important history, functional status)

2) Physical Examination
A. Measurement
Height, Weight, Head circumference, Plot & assess growth chart, Calculate height velocity, Request/
plot birth parameters, parent`s percentiles and ages at puberty
B. Systematic
HEENT, Upper limbs - Diagnostic facies
(General inspection) - Tanner stagging
- Nutritional status (obese/thin)
- Skeletal anomalities (pectus excavatum/scoliosis)
- Skin (cutis marmorata, atopic eczema, hyperkeratotic dry skin, fungal
infections, pustular folliculitis, vitiligo, seborrhoeic dermatitis)
- UL (manoeuvres: palm up (detect simial crease,clinodactlyl), check for
hyperextensibility (hypotonia)
- Fingers (brachydactyly-short fingers), 5th finger (hypoplasic mid-phalanx)
- Nails (clubbing in cyanotic heart disease)
- Palms (Simian creases)
- Blood pressure (elevated in occult renal disease)
- Joints (hyperflexibility, restricted movement: arthropathy)
- Head (microcephaly, brachycephaly, flat occiput, facial profile: fat, late
fontanelle closure)
- Eye (examine glasses for myopia, check vision with wearing glasses,
epicanthal folds, upward slant of palpebral fissures, prominent eyes:
coexistent hyperthyroidism, blocked-tear duct: infant, ptosis, squint,
nystagmus)
- Conjunctival pallor (iron deficiency, TAM, AML, ALL)
- Scleral jaundice (coexistent liver disease)
- Iris (Brushfield`s spots: white speckling of peripheral iris)
- Cornea (buphthalmos: large, cloudy, glaucoma, keratoconus)
- Visual fields (defect, CVA from cyanotic heart disease)
- Eye movement (nystagmus)
- Ophthalmoscopy (cataracts)
- Nose (small, flat nasal bridge)
- Mouth, chin (central cyanosis: various CHD, tendency to open mouth)
- Palate (short hard palate)
- Teeth (hypodontia,irregular placement,periodontal disease,dental caries)
- Tongue (protruding, fissured)
- Tonsils (enlarged causing OSA, absence: previous adenotonsillectomy)
- Ears (wear hearing aid, assess hearing loss (conductive/sensorineural,
small, overfolded upper helix, small/absent earlobes, low-set, eardrum:

83
chronic serous otitis media, atelectatic eardrum, tympanic membrane
scarring, permanent perforation, middle-ear cholesteatoma)
- Neck (short, pterygiumcolli, scoliosis, excess skin back of neck, low
posterior hairline, goitre(thyroid disease), torcollis (spinal cord
compression from atlanto-axial instability)
Chest - Inspection
- Scars (repair of CHD:, repair of tracheo-oesophageal fistula, insertion of
access port for chemotherapy for ALL, AML)
- Tanner staging in girls
- Sternal deformity: pectus excavatum or carinatum
- Palpate & auscultate praecordium
- Various forms of CHD, loud S2 with OSA, development of mitral valve or
tricuspid valve prolapse or AR)
Abdomen - Inspection
- Scars (repairs of GIT anomalies eg. duodenal atresia, pyloric stenosis,
Hirchsprung disease, omphalocele, imperforate anus; repairs of urinary
tract anomalities eg. vesicoureteric reflux, posterior urethral valve; renal
transplantation eg. dysplastic kidneys, glomerulosclerosis; others
operative condition eg. Crohn`s disease)
- Palpation
- Hepatomegaly (CCF)
- Splenomegaly (SBE)
- Hepatosplenomegaly (ALL, AML)
- Enlarged kidneys (hydronephrosis)
Genitalia - Tanner staging: measure penis length & testicular volume
- Penile abnomalies: hypospadias (infant), corrected hypospadias
- Testicular anomalies: cryptochidism, enlarged(seminoma), leukaemic
deposits
Lower limbs, Gait, Back - Lower limbs
- Inspection (Clubbing of toes (CHD), saddle gap, single plantar crease,
hallux valgus, hammer toes, fungal infection of nails (adolescents), pes
planovalgus)
- Palpation (ankle oedema- CCF with CHD)
- Back (short neck/neck webbing, bend over and touch toes for scoliosis)
- Neurological (Hypotonia, normal power, Long tract signs)-quadriparesis/
quadriplegia, Hyperreflexia (Spinal cord compression from atlanto-axial
instability, CVA/cerebral abscess complicating cyanotic CHD)
- Joint (hyperflexibility, restriction of movement)
A.Developmental assessment
Refer pg. 40. Most children with Down syndrome have developmental quotient (DQ) and later
intelligence quotient (IQ) in the range 50-70.

84
Meningitis

Definition:
- Inflammation of the meninges covering the brain, following infection of subarachnoid space.

Aetiology:
Infectious

A) Viral infection (commonest)


- Overall 2/3 of CNS infection are viral
- Enterovirus (80%), EBV, adeno virus, mumps
- Acute onset & vague: maculopapular rash (EV), parotid & mandibular swelling (mumps)
- Confirm by virology test/PCR
- Self-resolving, require only supportive treatment

B) Bacterial infection
- >80% bacterial meningitis are in children <16 years old in UK (5 -10% mortality), >10% of
survivors have long term neurological impairment
- Pathophysiology
- Usually follow bacteraemia
- Damage to meninges result from host response to infection (not from bacterial itself)
body release inflammatory mediators and activate leucocytes à endothelial damage à
increase permeability à cerebral edema, ↑ICP, ↓cerebral blood flow
- Severe consequences
Duration/Condition Causative organism
Neonatal - 3 months - Escherichia coli (E. coli)
- Group B Streptococcus (S. agalactiae)
- Klebsiella sp.
- Listeria monocytogene
1 month - 6 years - Haemophilus influenza (H. influenza)
- Streptococcus pneumoniae
- Neisseria meningitidis
> 6 years - Streptpcoccus pneumoniae
- Neisseria meningitidis
Fistulae/Shunt - Coagulase negative staphylococcus
(S. epidermidis, S. saprophyticus)
Immunocompromised - Fungal infection
- Low virulence organism
- Opportunistic organism
- Well known association between pneumococcal infections & H. influenza with sickle-cell
disease, asplenism or removal of spleen.

C) Fungal infection
Non-Infectious

Disease/Condition Underlying causes


Space-occupying lesion - Malignancy (metastatic spread of malignant cells)
- Haemorrhage (follow SAH)

85
Autoimmune disease - RA, SLE, Sjogren, Vasculitis (Kawasaki`s disease)
- Sarcoidosis
Drugs & contrast media - NSAIDS, amoxicillin, IV Ig, Methotraxate, Isoniazid, TMP/SMX
(Stimulates Type III, IV hypersensitivity reaction)
.

Route of Infection (entry of pathogens):


Blood (blood brain barrier, - Infective endocarditis
choroid plexus, facial vein) - Bronchiectasis
*commonest route - Abscess
- Septicaemia
Peripheral nervous system - Rabies
(PNS) - Herpes simplex
- Poliovirus
Direct implantation - Lumbar puncture
- Ventricular shunt
- Corneal/Other transplant
- Open fracture
Local extension - Mastoiditis
- Chronic suppurative otitis media (CSOM)
- Myelomeningocoele

Risk Factors:
Environment - Overcrowded closed communities, schools, day cares
- Low socio-economic status dt malnutrition and low birth weight
Host - Male are commonly affected
- Too young (preterm) or too old
- Complement or antibody deficiency
- Immunosuppresion: Carcinoma, AIDS, no effective spleen, sickle cell
disease (autosplenectomy), hypo-gammaglobulinemia, DM
Head - Head injury (especially basal skull, cranial or spinal surgery)
- Encephalocele or leaking myelomeningocele
Septic site - Blood route (eg. pneumonia, UTI)
- Local route (eg. sinusitis, mastoiditis, otitis media)
Foreign body - CSF shunt

Clinical Features
- Early stage, there if non-specific and makes early diagnosis difficult.
Symptoms Signs
Non-specific Meningism
- Fever, Irritability, lethargy, drowsiness - Neck stiffness
- Vomiting, poor feeding - Lying with an arched back (opisthotones)
- Seizure - Kernig`s sign +ve (stretch of meninges)
- Child lying supine & with hip, knee flexed à
Meningism back pain on extension of knee
Classical triad: - Brudzinski`s sign +ve
- Headache, Photophobia, Stiff neck - Child lying supine & neck flexed à flexion of
the knee and hip

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↑ICP ↑ICP
- Irritability, drowsiness, vomiting, fits - Bulging anterior fontanelle
- Reduced consciousness, coma - Papilloedema
- Bradycardia, hypertension
- Irregular respiration
- Sunset eyes (squint CN6 palsy)
Septicaemia Septicaemia (signs of shock)
- Fever, malaise, arthritis, rash - Tachycardia
- Odd behavior, DIC (bleeding) - Hypotension
- Purpuric skin lesion - Tachypnea
- Oligouria
- Prolonged capillary refill time (>2s)

Complications:
Brain Local cerebral infarction
- May result in focal or multifocal seizures (increase risk of epilepsy)

Subdural effusion
- Accumulation of high protein & xanthochromic fluid in the subdural region
- Usually sterile, over temporoparietal region
- Associated with H. influenza or pneumonoccal meningitis
- Usually resolve spontaneously

Cerebral abscess
- CF usually suddenly deteriorates with emergency of SOL
- Confirmed by CT scan drainage of the abcess is required

Hydrocephalus
- Impaired resorption of CSF (communicating)

Neurological lesion
- Cranial nerve palsy: commonly 3,4,6 monoplegia/hemiplegia

Meningococcaemia (Meningococcal meninigitis)


- Waterhouse-Friderichsen syndrome/ hemorrhagic adrenalitis/ fulminant
meningococcemia: Adrenal gland failure due to bleeding into the adrenal
glands, commonly caused by severe bacterial infection. Typical pathogen
is Neisseria meningitides.
- Sudden onset of acute fever, coma, collapse, cyanosis, petechial
haemorrhage of skin/mucous membrane, bilateral adrenal hemorrhage
- Death may occur within hours due to shock, toxaemia, DIVC
- Diagnosis confirm by blood culture
- Treatment is urgent and immediate
Ear Hearing loss
damage to the cochlear hair cell
Vessel Local vasculitis
may result in cranial nerve palsies or other focal lesions

87
Early complications Late complications
- Cerebral infarction - Cerebral palsy
- Seizure - Blindness
- Cerebral edema - Deafness
- Cerebral abcess - Mental retardation
- Local vasculitis - Behavior problem
- Meningococcaemia - Epilepsy
- DIC, Coagulopathy - Hydrocephalus
- Shock - Developmental delay
- SIADH

Investigation:
Lumbar puncture - Obtain CSF to confirm diagnosis
- Send for biochemistry test (cell count, protein, sugar)
- Gram stain, culture and sensitivity, AFB, antigen test
- Contraindicated in:
- Cardiorespiratory arrest
- Haematological unstablity
- Focal neurological signs
- Signs of raised ICP:
- Coma, hypertension, bradycardia, pappiloedema, pintpoint pupil
- Local infections
Blood test - FBC (Hb, MCH, MCV for anaemia, WCC for infection)
- ESR/CRP (signs of inflammation)
- RP (hydration status, electrolyte imbalance)
- LFT/CP (nutritional status, liver impairment, coagulopathy)
- RBS (hypoglycaemia)
- Blood gas (metabolic acidosis)
Culture & Sensitivity - Blood, CSF, urine samples

Rapid antigen screen/ PCR - Virology screening (a serology diagnosis can be made on
convalescent serum 4-6 weeks after the presenting illness.
CXR, Mantoux test - If suspected for TB

Head CT/ Brain MRI, EEG - Head CT is indicated when:


- Prolonged depression of consciousness
- Prolonged focal or late seizures
- Focal neurological abnormalities
- Enlarged head circumference
- Suspected subdural effusion or empyema

88

CSF findings in various CNS infections
Condition Appearance Pressure White cell Protein (g/L) Glucose
(cm H2O) (/mm3) (% of blood sugar)
Normal neonate Maybe 5 -10 up to 30 0.5 -2.0 > 60%
xanthochormic
Normal Infant Clear 5 - 10 up to 10 0.2 -1.0 >50 %
Normal child >1 y/o Clear 5 - 10 <10 0.15 - 4.0 > 50%
Acute Bacterial Turbid Usually 100 - 60,000 PMN 0.18 - 4.0 < 40 %
meningitis elevated predominate
Partially treated Usually clear Normal or 1- 10,000 PMN predominate 0.8 -2.0 Normal or low
bacterial meningitis elevated unless treated for extended
period
TB meningitis Hazy, may be Usually 10-500 PMN predominate 0.6 - 6.0, Higher in Very low especially if
viscous elevated initially, followed by obstruction treatment delayed
lymphocyte
Fungal Hazy, may be Usually 25- 500 PMN predominate 0.4 - 4.0 <50 %, lower if
viscous elevated initially, mononuclear cell treatment delayed
predominate later
Viral meningitis/ Usually clear, Normal, PMN early, mononuclear cell 0.4 -1.5 Generally normal.
meningoencephalitis may be slightly predominate later. Rarely May be low in some
hemorrhagic elevated >1000 except in eastern viral (15-20% in
equine mumps)
Abscess Turbid Elevated Usually normal unless Usually normal or Low
epidural or rupture into mildly elevated
ventricle
Brainstem encephalitis Usually clear Usually ~240/mm3, lymphocytes Mildly elevated in Only mildly reduced
normal predominate in 58% of 85% of cases, in 20 % of cases
cases normal in others

89
Management:

1. Supportive treatment
- Monitor vital signs and input/output 4 hourly
- Nil by mouth
- Careful fluid balance required. Usually a maintenance IV fluid is sufficient. Only if SIADH
occurs, reduce to 2/3 maintenance for the initial 24 hrs. Patient may need more fluid if
dehydrated. If fontanel hasn`t close, note daily head circumference. Ultrasound ± CT scan (if
effusion or hydrocephalus is suspected)
- Fit chart
- Daily CNS assessment is essential
- Patient must be observed for 24 hrs after stopping therapy, discharged if no complication

90
2. Medical Management
i) Antibiotic
- Remember to use the correct dosage af antibiotic that will penetrate the CSF
- Start antibiotics ASAP (normally after LP)
Recommended antibiotic therapy according to likely pathogen
Age Group Initial Antibiotic Likely Organism Duration (if uncomplicated)
< 1 month C Penicillin + Cefotaxime Grp B Streptococcus 21 days
E. coli
1 - 3 months C Penicillin + Cefotaxime Group B Streptococcus 10 - 21 days
E. coli
H. influenza
Strep. pneumoniae
> 3 months C Penicillin + Cefotaxime, H. influenzae 7 - 10 days
OR Ceftriaxone Strep. pneumoniae 10 - 14 days
N. meningitides 7 days
Note:
・ Review antibiotic choice when infective organism has been identified.
・ Ceftriaxone gives more rapid CSF sterilisation as compared to Cefotaxime or Cefuroxime.
・ If Streptococcal meningitis, request for MIC values of antibiotics. *MIC = minimal
MIC level Drug of choice: inhibitory
- MIC < 0.1 mg/L (sensitive strain) C Penicillin concentration
- MIC 0.1-< 2 mg/L (relatively resistant) Ceftriaxone or Cefotaxime
- MIC > 2 mg/L (resistant strain) Vancomycin + Ceftriaxone or Cefotaxime
・Extend duration of treatment if complications eg. subdural empyema, brain abscess.

ii) Use of Steroids to decrease the sequel of bacterial meningitis


- There is evidence that use of steroids can reduce the sequel of meningitis especially
sensorineura; deafness in H. influenza meningitis. There may also be of benefits in S.
pneumonia meningitis.
- The best effect is achieved if the steroid is given before or with the first antibiotic dose
- Dosage: Dexamethasone 0.15mg/kg 6 hourly for 4 days or 0.4mg/kg 12 hourly for 2 days
- Our recommendation is to give steroid if the CSF is turbid and the patient has not been given
any prior antibiotics.

iii) Persistent Fever in a patient on treatment with meningitis


- Thrombophlebitis and injection sites eg: intramuscular abscess
- Intercurrent infection eg. pneumonia, UTI, nosocomial infection
- Resistant organisms. Inappropriate antibiotics or inadequate dosage
- Subdural effusion/empyema or brain abscess
- Antibiotic fever

iv) Management of increase ICP


- During first 18 -24 hrs, there is cerebral hyperaemia, thus cerebral protection may be indicated
- 30⁰ bed head elevation
- Antipyretics agents if febrile
- Avoid frequent and vigorous tracheal suctions
- Correction of hyponatraemia/SIADH
- Use IV mannitol judiciously (osmotic diuretics to prevent/treat acute renal failure, reduce
cerebral edema/ ICP

91
v) Partially treated bacterial meningitis
- Children are frequently give oral antibiotics for a non-specific febrile illness
- If they have early meningitis, this partial treatment with antibiotics can cause diagnostic
problem
- CSF examination shows highly elevated WCC but culture will be negative
- Rapid antigen tests & PCR are helpful

vi) Follow up (Long term follow up is essential)


- Note development of child at home and at school
- Note head circumference
- Ask for any occurrence of fits or any behavioral abnormalities
- Assess vision, hearing and speech( if necessary, do an audiometry in assessment of hearing
especially in those with speech delay)
- Follow up until child speak normally or intelligible to others (usually until 4 years old)
- Prophylaxis rifampicin for all household contact for meningococcal meningitis

vii) Prognosis depends on:


- Age: worse in younger patients
- Duration of illness prior to antibiotics treatment
- Specific organism: more complication in H. influenza & S. pneumonia
- Presence of focal signs

Short Notes on Bacterial Meningitis:

Meningococcal Menigitis
- Neisseria meningitides
- Reduce incidence dt introduction of conjugate vaccine agst grp A & C (but still no effective vaccine agst grp B)
- Emergency, can kill previously healthy child within hours
- Associate with speticaemia & purpuric rash (lesions are non-blanching on palpation, irregular shape & size,
necrotic centre)
- Lower risk of long term neurological sequel and recover fully
- Common in middle east, ask about travel history

Haemophilus Meningitis
- Immunization has been highly effective (Hib B vaccine)
- Now it is a rare cause

Pneumonoccal Meningitis
- Increased incidence
- >30% develop neurological impairment
- Associated with sickle cell disease, asplenism or removal of spleen

Tuberculous Meningitis
- History: Insidious onset, 2-3 weeks, minimal meningism, TB contact, chronic cough/illness, ESR>100
- Suspected by +ve Mantoux test (>10mm in 48-72 hours)
- Abnormal CXR
- Confirm diagnosis by LP with Ziehl-Nielson stain
- Start muti-antimicrobial regime ASAP due to increased morbidity & mortality

92
Lumbar Puncture (Spinal tap/ CSF fluid tap)
Definition:
A procedure to collect CSF. It involves inserting a needle between the 3rd and 4th lumbar
vertebrae in the back and extracting a sample of fluid.

Indications:
1. Diagnostic method - Meningitis/encephalitis
- GBS
- Multiple sclerosis (chronic, demyelinating disease caused by
inflammation, destruction & scarring of sheath covering nerve
fibers in brain & spinal cord)
- CNS syphilis
- Certain forms of hydrocephalus
- Lymphoma, leukemia or other cancers involving brain or CNS
- Bleeding in the brain or spinal cord
- Any disorder affecting the nervous system
2. Others - Drain spinal fluid to lower ICP
- Administer dye for imaging studies
- Administer medications (eg. chemotherapy/epidural anesthesia)

Contraindications:
- Increase ICP (S&S , raised BP, fundoscopic sign)
- Bleeding tendency : Platelet count <50,000/mm3 or Prolonged PT and APTT
- Cardiorespiratory instability
- Focal neurological signs
- Local infections at site of LP

Complications:
- Pain or abnormal burning sensations in the legs OR post-spinal tap headache
- Bleeding into CSF (Spinal, epidural, subdural or subarachnoid hematomas)
- A local infection at the site
- CNS infections
- Brain herniation associated with increase ICP
- Inflammation of the arachnoid mater
- Temporary paralysis of a cranial nerve
- Rupture of the soft, central portion of the intervetebral disk (nucleus pulposus)

93
Preparation:
- Sterile set
- Sterile bottles for CSF , bottle for RBS
- Spinal needle 20-22G, lenth 1.5 inch with stylet (length 3.5 inches for children >12 y/o

Procedure:
- Give sedation (midazolam) apply local anaesthetic
- Place child in lateral recumbent position with neck, body, hips and knees flexed.
- Monitor oxygen saturation continuously.
- Visualise vertical line between highest point of both iliac crest and its transaction with the
midline of the spine (at level L3-4)
- Clean area with standard aseptic technique using povidone iodine and 70% alcohol.
- Gently puncture skin with spinal needle at the identified mark and pointing towards the
umbilicus. The entry is distal to the palpated spinous process of L4.
- Gently advance a few millimeters at a time until there is a blackflow of CSF (there may be a
`give` on entering the dura mater before the CSF bckflow). Collect CSF in designated bottles.
- Gently withdraw needle, spray with op-site, cover with gauze and bandage.
- Take RBS
- Ensure child lies supine for next 4-6 hours, continue monitoring till s/he recovers from sedation.

Laboratory Findings:
CSF - Appearance
- Pressure
- Microbiology
- Gram stain
-C&S
- India ink test : detection of meningitis caused by Cyptococcus
neoformans antibody mediated test (latex agglutination, treponemal
titres, cocciciodes antibody)
Latex agglutination test - Determines the presence of
- H. Influenza, Staphylococcus aureus, E. coli, Group B strep, Listeria sp.
- PCR has been a great advance in diagnosis of some types of meningitis. It
has high sensitivity and specificity for many infections of the CNS, is fast
and can be done with small volumes of CSF. Even though testing is
expensive, it saves cost of hospitalization.
Cytology - Identify the presence of maglinant cells

Biochemistry - Glucose, total protein, chloride level


- Glutamine (↑ involved with hepatic encephalopathies, Reye`s syndrome,
hepatic coma, cirrhosis, and hypercapnia)
- Lactate (↑ presence of cancer of CNS, MS, heritable mitochondrial ds,
low BP, low serum phosphorus, respiratory alkalosis, idiopathic seizures,
traumatic brain injury, cerebral ischemia, brain abscess, hydrocephalus,
hypocapnia or bacterial meningitis)
- LDH (distinguish bacterial meningitis which often associated with high
level, from those of viral origin in which the enzyme is low or absent)
- IgG synthetic rate is calculated from measured Ig G and total protein
level; Elevated in immune disorders (MS, transverse myelitis &
neuromyelitis optica or Devic`s disease)

94
Syndrome of Inappropriate Antidiuretics Hormone (SIADH)

Introduction:
- Occurs when excessive levels of antidiuretics hormone (ADH) are produced
- Causes the fluid retention in the body and hyponatraemia

Aetiology:
Tumours - Small cell lung CA
- Prostate tumor
- Thymus tumor
- Pancreas tumor
- Lymphomas
Pulmonary lesion - Pneumonia
- Tuberculosis (TB)
- Lung abscess
Metabolic - Alcohol withdrawal
- Prophyria
CNS - Meningitis
- CNS tumours
- Head injury
- Subdural haematoma
- Cerebral abscess
- SLE vasculitis
Drugs - Chloropropamide
- Carbamezapine
- Cyclophospahmide
- Phenothiazines

Diagnosis:
- Plasma dilutional hyponatraemia (<130 mmol/L)
- Low plasma osmolality (<270 mmol/kg) [Normal range: 285-295 mmol/kg)
- Inappropriate urine osmolality(>150 mmol/kg)
- Continued urine sodium excretion

Treatment:
- Treat underlying cause
- Symptomatic Tx
- Restrict fluid intake to 500-
1000mL/day.
- If not adequate give
demeclocycline( as an
inhibitor of arginine
vasopressin)
- Plasma osmolality,
sodium & body weight
should be measured
frequently
- If very severe give
frusemide with extra
caution 95
Encephalitis/Encephalopathy
Definition:
- Inflammation of the brain parenchyma ± meninges

Aetiology:
- Unknown
- Possible viral or bacterial infections
- Direct invasion of the cerebrum by neurotoxic virus
- Delayed brain swelling following a disordered neuroimmunological respose to an antigen,
usually a virus (post-infectious encephalopathy)
- Slow virus infection; HIV, Subacute sclerosing panencephalitis(SSPE) following measles

Viral Bacterial
1. Enterovirus 1. Mycoplasma
- Poliovirus 2. Borrelia burgdorferi (Lyme disease)
- Coxsackie virus 3. Bartonella nenselae (cat scratch disease)
2. Respiratory virus 4. Rickettsial infection
- RSV
- Parainfluenza virus
3. Arbovirus (arthropod-borne virus)
- Dengue virus (epidermic outbreak)
4. Herpes virus
- Herpes Simplex virus (HSV)
- rare but devastating
5. EBV, CMV
6. HIV
7. Measles (SSPE)
8. Mumps, Rubella

Pathology:
- Frequently non-specific
- Compromise brain swelling, vascular congestion, cellular infiltration, cerebral edema

Arbovirus Tend to be diffuse, leading to extensive neurological damage, microglial


proliferation
HSV Haemorrhagic necrosis of one or both orbital surface of the
frontal/frontaltemporal lobe
Mumps Produce ependymal damage à stenosis of the aqueduct of Slyvius

96
Clinical Features:
- Usually acute onset
- Full recovery within a few days or weeks
- Most devastating illness à death or recovery with permanent neurological sequel
* It is not possible to clinically differentiate viral meningitis vs encephalitis vs myelitis

Symptoms Sign
- Fever, headache, malaise, dizziness - Various neurological sx
- Altered consciousness - Depend on the site & extent of the
- Behavioral change inflammation
- Neck stiffness - Such as paraplegia, sensory disturbance,
- Often seizure, mental confusion, stupor, speech difficulty, involuntary movement,
delirium ataxia, neurologic bladder
- Associate with skin rash (measles, varicella)

Diagnosis:
- Dx by exclusion except for the epidemic encephalitis or following of exanthematous fever
- Confirmatory by CSF virology
- EEG & MRI may show the focal change in the frontal/temporal lobe

Management:
- Mainly is supportive (monitor hydration status, careful nursing)
- Antiviral: All children with encephalitis should cover by acyclovir (HSV - devastated Cx)

Lennox-Gastaut syndrome
- Childhood epileptic encephalopathy
- Onset 2-6 years old
- Associated with status epilepticus (seizure >30 minutes)
- Brain distressed by frequent seizure and multiple different seizure type
- Causing mental retardation & behavioral problem, slow global development
- Associated Seizure: 1. Tonic (90%)
2. Myoclonic
3. Atonic
4. Absence
5. Complex partial
6. Tonic clonic
- Aetiology: Unknown, tuberous sclerosis, hereditary metabolic ds, encephalitis, meningitis,
Hypoxic ischemic encephalopathy (HIE), birth injury
- Diagnosis:
- EEG (abnormal EEG: paroxysmal fast activity, generalized slow spike & wave discharge (1.5 HZ)
- MRI
- CT Scan
- Treatment
- Sodium valproate
- Benzodiazepine

97

Fever/ Headache

Meningitis Encephalitis

Symptoms Symptoms Reye`s Syndrome


- Photophobia - Behavioral change - Caused by viral infection
- Neck stiffness - Altered consiousness (frequently influenza or
varicella) + aspirin
Signs Signs Cx - Aetiology is obscure
- Neck stiffness - Neurological Sx
- Characterized by
- Kernig`s sign - Rash
- Rapid onset of severe
- Budzinski`s sign
encephalopathy (sign of
decerebrate rigidity)
- Hepatic dysfunction
CSF CSF (hepatomegaly, ↓Glu, ↑PT,
CT ↑ transaminase, ↑ NH3)
MRI - Following URTI à child
- Antibiotics, develop fit & sink into deep
EEG
antiviral or
coma within 24-48 hours
antifungal
- Hydration
- Antiviral
- Hydration

98
Cerebral Palsy

Definition:
- Disorder of movement & posture due to a non-progressive lesion of motor pathway in the
developing brain (<2 years old)

Epidemiology:
- Most common cause of motor impairment in children
- Incidence: 2 per 1000 livebirths

Pathology:
- Cerebral atrophy, often with cavity formation in the subcorticla white matter
- Porencephaly (an abnormal communication between the lateral ventricles and the surface of
the brain)
- Degeneration of basal ganglia

Aetiology:
Antenatal (80%) Intrapartum (10 %) Pospartum (10%)
1. Cerebral dysgenesis 1. Birth asphyxia (HIE) 1. Preterm infant
2. Failure of migration of - APGAR score - Periventricular leucomalacia
grey matter - Respiratory distress (PVL): ischaemic necrosis of
3. Cerebral malformation - Chord prolapsed periventricular white matter
- Congenital cyst - Chord strangulation
- Fusion defect - Meconium aspiration 2. Intraventricular/
4. Congenital infections subependymal haemorrhage
- TORCHES 2. Trauma
5. Vascular occlusion - Instrumental delivery 3. Cerebral anoxia/ischaemia
- Abruption placenta
- Placenta praevia 4. Meningitis/encephalitis/
6. GDM, PIH encephalopathy

5. Head trauma/non-accidental
injury (shaken baby
syndrome)

6. Symptomatic hypoglycemia

7. Hydrocephalus

8. Hyperbilirubinaemia
(Kernicterus)

* In many cases, a definite cause cannot be accurately determined

99
Clinical features:
Symptoms Signs
- Feeding difficulties - Delayed motor milestones
- Oromotor discoordination - Abnormal limb tone & posturing
- Slow feeding - Abnormal gait (hemiplegic gait)
- Gagging & vomiting - Once walking is achieved
- Developmental delay in language & social - Hand preference (<12 months old)
skills - Signifies hemiparesis
- Persistence of primitive reflex (> 6 months)
- Becomes obligatory

* Symptoms and signs are not static & a changing pattern of physical symptooms is observed
with increasing age for a considerable period of time

Associated Problems:
General - Learning difficulties/ intellectual impairment (60%)
- Speech and language disorders (from combination of)
- Hearing loss
- Muscle discoordination
- Learning impairment
- Behavioral disorders
- Hyperactivity
- Poor concentration
- Temper outburst
Head - Epilepsy (40%)
- Visual impairment (20%): refractive errors & cortical damage
- Strabismus, squint, mylopia, nystagmus
- Hearing loss (20%)
Respiratory - Aspiration pneumonia
- Hypostatic pneumonia
- Chest infections
GIT - Sucking & swallowing difficulty
- FTT
- GERD
Others - Urinary incontinence
- Constipation
- Menstruation problem
- Pressure sores

Types of Cerebral Palsy:


It can be classified based on
1. Motor function
2. Topographical distribution
3. Severity level
4. Gross Motor Function Classification System (GMFCS)

Adapted source from : http://cerebralpalsy.org/about-cerebral-palsy/types-and-forms/

100

(1) Classification based on motor function
Spastic (70 %) Ataxic (10%) Dyskinetic (10%) Mixed (10%)
- Damage to the upper motor neuron - Affects coordinated movements, - Pathophysiology - Any combination of
pathway: pyramidal & corticospinal balance and posture - Perinatal injury by kernicterus the different types
pathway (common)à damage to basal ganglia
- Pathophysiology: or extrapyramidal pathway - Commonest is a
- Clinical features: - Genetic cause commonest - Hypoxic ischaemic encephalopathy (HIE) mixture of Spastic &
- Persistent primitive reflex - Cerebellar dysfunction or its pathways at term Athetoid
- Initial hypotonia (esp at head & neck)
- Hypertonia (spasicity): tight fisting of the - Clinical features (usually symmetrical) - Clinical features
hand, clasp knife spasticity Early - Constant involuntary movements
- Up-going plantar reflex (Babinski`s - Hypotonia - Athetosis
positive) after 2 years old - Poor balance - Dystonia
- Scissoring of legs when the infant is grown - Delayed motor development - Chorea
up (spasicity of extensor/adductor muscle Late - Choreoathetoid
of LL) - Uncoordinated & involuntary - Poor postural control (flopiness)
- Equinovarus deformity of foot (dorsiflex & movement - Delayed motor development
inversion) - Rigidity - Intellect relatively unimpaired, no seizure
- Windswept hip deformity (ipsilateral - Ataxic gait (broad base)
internal rotation & adduction of hip joint - Obligatory tonic neck reflex Athetosis
with external rotation & abduction of - Control of eye movement & depth - Repetitive involuntary, slow, sinous,
contralateral hip joint) perception can be impaired writhing movements @ arms, legs,
- Fine motor skills requiring hands
- Forms of spastic cerebral palsy coordination of eyes and hands eg. Dystonia
- Hemiplegia writing are difficult - Impairment of muscular tonus
- Diplegia (truncal >limbs)
- Quadriplegia Chorea
* Refer Classification II (topographical - Irregular movement, non-repetitive,
distribution) more jerky and shaky
Choreoathetoid
- Combination of chorea + athetosis
- irregular movement but twisting and
curving

101
(2) Classification based on topographical distribution
Hemiplegia - Aetiology:
- 2/3, congenital: Perinatal stroke, Cerebral malformation
- 1/3, Acute postpartum event
- Destruction of brain at level of the cortex or internal capsule
- Clinical features (usually appears at 4 -12 months of age):
- Unilateral involvement of arm & leg (prefer use only one side of the body)
- Arm usually affected more than leg, face spared
General Limb signs (affected side)
- Initially flaccid & hypotonic Hand
- Then, hypertonia develops - Fisting of affected hand
- Intellectual level is low than - Asymmetric reaching
normal - Flexed arm
- Pronated flexed forearm
- Flexed wrist
Leg
- Limping when walk + circumduction
of affected leg
- Tiptoe walk (toe-heel gait)

-
Diplegia - Aetiology: Preterm infant
- Involvement of all for limbs but legs are affected more then arms
- Hand function appears relatively normal in later life
- Clinical features:
- Floppy in the first few month of life
- Gradually increase the extensor posture
- Clumsiness in grasping
- Walking is abnormal
Quadriplegia - Aetiology: HIE & Congenital event
- Involvement of all four limbs with fairly similar degree (arms > legs)
- Clinical features:
- Poor head control
- Low central tone
- Extensor posturing (trunk involvement)
- Disused atrophy
- Associated problems
- Seizures
- Microcephaly
- Moderate to severe intellectual impairment
Monoplegia - Affect only 1 limb
Paraplegia - Lower half of both including both legs
Triplegia - Involve 3 limbs
Double hemiplegia - One side of body more affected than the other
Pentaplegia - All 4 limbs + neck & head paralysis
- Often accompanied by eating and breathing complications




102

(3) Classification based on severity level
Mild - Child can move without resistance
- Daily activities not limited
Moderate - Child will need braces, medications, adaptive technology to accomplish
daily activities
Severe - Require wheelchair.
- Have significant challenges in accomplishing daily activities
No CP - Has CP sign but impairment happens after completion of brain development
- Classified under incident eg. traumatic brain injury/encephalopathy

(4) Classification based on Gross Motor Function Classification System (GMFCS)
Level I Walk w/o limitations
Level II Walks with limitations:
- Cannot walk for long distance
- Difficulties in balancing , thus cannot run and jump
- May need mobility device
Level III - Walks with adaptive assistance
- Require hand held mobility device assistance (indoor)
- Use wheelchair outdoors
- Can sit by own
Level IV - Use of powered mobility assistance
- Sit supported
- Transported in wheelchair
Level V - Severe head and trunk control limitations
- Extensive use of assisted technology device
- Self-mobility by powered wheechair

Diagnosis
- Not easy to detect in early of life
- Suspected when:
- Risk/etiology affected the brain
- Delay in reaching normal development milestone
- Persistent remain of primitive reflex
(moro reflex, grasping reflex, stepping reflex à cycling movement)
- Less facial expression
- Abnormal gait & posture

Investigation
- Imaging studies (neonatal brain sonography: brain MRI)
- can help to evaluate brain damage and to determine those at risk for cerebral palsy BUT
support a definitive diagnosis of cerebral palsy are lacking
- EEG is useful in evaluating seizure condition
- Hearing and vision screening

103
Management
There is no curative treatment. An early diagnosis can be useful to help get necessary support
(and funding) in place. Once the child has been diagnosed, then their care is taken care of by a
type of MDT known as the CDS (Child development services). This essentially comprises of the
paediatricians, social workers, physiotherapists, occupational therapists, psychologists,
dieticians etc.

- Aimed to increase the quality of life


- Parents should be informed details of the diagnosis ASAP
- Multidisciplinary team approach (MDT) (doctors, parent, community)
- Medical:
- Complete and regular assessment for the child
- Muscle relaxant (diazepam, baclofen, dantrolene sodium)
- Orthopeadic: correct deformities
- Neurosurgery: ↓ spasticity or disabling dystonic movement
- Psychiatry (psychological and social problems : psychologist, social workers
- Education
- Rehabilitation
- Physiotherapy: maintain full range of movement, functions, to prevent contractures
- Speech therapy: oral training (control of drooling)
- Caring at home
- Employment when reach adult life
- External Aid (designed shoes, ankle foot orthoses may be required to provide stability to the
joints in a child who is learning to stand and walk): wheelchairs, splinter

Prognosis
- Cure is not possible
- Based on patern of evolving signs & child`s developmental progress

Cerebral Palsy Long Case (Template)


1) History
- Presenting complaint
- Reason for current admission
a) May be complications of CP, eg. swallowing problem, aspiration pneumonia, seizures
b) May be for elective surgery, eg. tenotomy (correction of contractures), tendon transfer
(correct deformity from muscle imbalance)

- HOPI
- SOCRATES about presenting complaint(s), TRO other differential diagnosis

- Current Functional Status


Intellectual abilities Present developmental status, current placement in education,
domestic situation, employment
Behaviour Hyperactivity, neglect (eg. depression), temper outburst, low
concentration, lack of self-esteem, parental overprotection
104
Vision Cortical visual impairment, strabismus, myopia, hemianopia
Speech, hearing & Expressive or receptive dysphasia, dysarthria, athetoid movements,
communication use of aids eg. communication boards and computers
problem
Activity of Daily Bathing, cleaning teeth, combing hair, dressing, writing and other
Living (ADL) hand usage, toileting, menses
Feeding & Nutrition Sucking and swallowing ability, tube feeds, gastrostomy, gastro-
oesophageal refux, aspiration pneumonia, failure to thrive
Seizures Type, duration, frequency, usual treatment including side efects,
compliance and drug levels, last seizure
Mobility - Walking ability (community, household or non-functional ambulator)
gait pattern, wheelchair mobility)
- Skeletal problems (eg. kyphoscoliosis, lumbar lordosis,
spondylolisthesis, hip subluxation and dislocation,
pseudoacetabulum formation, contractures, unequal leg length)
- Abnormal posturing
Other problems Urinary incontinence, constipation, management of menses, chest
infections, pressure sores, hypostatic pneumonia

- Past-medical history
- Any illness in infancy eg. meningitis/encephalitis, severe jaundice, severe sepsis
- Any hospitalisation/neonatal ICU admission/neurosurgery

- Paediatrics History
Birth history - Relevant antenatal, intrapartum & post-natal history
(look for possible - Maternal past history of miscarriages or infertility.
causes) - Pregnancy: hyperemesis, hypertensive disease of pregnancy,
teratogenic medications, placental problems, clinical evidence of, or
exposure to, infection (eg. TORCH), quality of fetal movements,
gestational age.
- Delivery: presentation (eg. breech, face), instrumental delivery, Apgar
score,resuscitation required, birth weight, oxygen supply, nursery care.
- Neonatal period: respiratory distress, feeding difculties, seizures,
hyperbilirubinaemia (phototherapy or exchange transfusion),
intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL),
hydrocephalus, retinopathy of prematurity (ROP).
Immunisation Any delays, local doctor`s attitudes, parents` understanding of
importance of immunisation.
Developmental - Any developmental delay
- Assess gross motor, social, language
- Ascertain quality of attainment!
eg. bottom shuffling, development of early hand preference, splaying
of fingers when attempting grasp
Dietary Breastfeeding, weaning, feeding difficulty, food history

- Family history (any siblings with CP, neurological disorders)

105
- Current management
- Recent management in hospital
- Usual treatment at home
- Usual doctors seen
- Compliant with follow up?
- Frequency of therapy (physiotherapy, occupation therapy, speech therapy)

- Social History
- Impact on parents and siblings
- Disruption to family routine
- Family financial considerations (e.g. private health insurance, visits to multiple specialists,
cost of hospitalisations, surgical procedures, aids, home modifcations, drugs, benefts
received, such as Child Disability Allowance),
- Social supports (social worker, extended family, respite care, involvement of Spastic Centre,
self-help groups)
- Legal proceedings surrounding perinatal care
- Understanding of problems and prognosis: Parents` and siblings` understanding; degree of
education regarding CP
- Special school/sheltered workshop, self-help group

2) Physical Examination
A. General Observations
- Dysmorphic features (eg. chromosomal anomalies).
- Parameters: head circumference (often obvious microcephaly), weight (often failing to thrive), height
(usually decreased), progressive percentile charts.
- Posture (eg. fisting, increased extensor tone, asymmetric tonic neck reflex [ATNR], hemiplegic,
quadriplegic).
- Movement:
(a) involuntary (eg. choreoathetoid movements, dystonic spasms, seizures)
(b) voluntary (eg. immature gait pattern with wide base, up on toes, arms out for balance; hemiplegic,
diplegic gaits; note posturing of arms when walking)
- Asymmetry (eg. hemiatrophy: look at the size of the thumbnails and the great toenails for subtle clues
to asymmetry)
- Behaviour (eg. lack of interaction with environment, crying)
- Eye signs (eg. squint, nystagmus)
- Bulbar signs (eg. dysarthria, drooling)
- Interventions (eg. nasogastric tube, gastrostomy tube, scars of orthopaedic procedures)
- Clothing (eg. nappies in child over 4 years old)
- Peripheral aids (eg. wheelchair, splints, orthoses)
* Look for bed sores
B. Demonstration of signs of CP
- If possible, perform a standard gait examination.
- If the child cannot walk, but can crawl, look for abnormal crawling:
(a) those with spastic diplegia or quadriplegia—buttock crawling and `bunny-hopping` (jumping
while on knees)
(b) those with hemiplegia - asymmetrical crawl

106
- Gross motor `180°manoeuvre`, incorporating primitive reflexes:
(a) lying supine (assess position adopted, e.g. ATNR)
(b) pull to sit by hands (to assess head lag and grasp)
(c) sitting (assess sitting ability, then lateral propping)
(d) hold up vertically, under axillae (to detect increased extensor tone, scissoring, automatic walking)
(e) tilt sideways (to assess head righting)
(f) ventral suspension (to detect excessive extensor tone)
(g) parachute reflex (to detect asymmetry)
(h) place prone (to detect back arching)
- Inspect carefully for tendon release scars
- Palpate muscle bulk in each muscle group
- Tone: as above, plus assessment of upper and lower limbs, and evaluation of contractures (eg. tight
hip adductors, and tendon achilles)
- Power: voluntary movement, functional power (grasp of toys, cloth cover test)
- Reflexes: the head should be held in the midline (eg. by an examiner) so that an ATNR does not give a
false impression of unilateral hypertonia; note whether there is any crossed adductor reflex, spread of
reflexes, clonus or upgoing plantar responses.

C. Complications of CP
- Measure the head (for microcephaly, or macrocephaly due to hydrocephalus)
- Check the vision, visual felds and extraocular movements (for myopia, squint)
- Check the hearing (for sensorineural deafness)
- Check the ears (for chronic serous otitis media)
- Ask to check the gag refex (bulbar dysfunction)
- Look at the teeth (for dental caries)
- Look at the back (for kyphoscoliosis)
- Inspect and auscultate the chest (for chest infection)
- Palpate the abdomen (for constipation)
- Examine the hips (for dislocation)
- Screen nutritional status (demonstrate fat and protein stores)
- Perform a functional assessment for activities of daily living (eg. ofer cup, spoon, fork, knife, comb,
toothbrush; ask the child to put on a piece of clothing)
- Assess other areas of development (social & language)

- Summary
1) Classify type of CP based on :
- Motor function
- Topographical distribution
- Severity level
- GMFCS
2) List associated problems
- Poor swallowing, chest infection, urinary incontinence, behaviour problems, contractures etc.
- Functional status: ADL, Mobility
- Current management
3) Postulate underlying causes (if confident)
à Antenatal/perinatal/Postnatal

107
3) Discussion
- Differential diagnosis for Global Developmental Delay:
1. Hypothyroidism
2. Chromosomal anomaly
3. Structural brain disorder
4. Cerebral Palsy
5. Congenital infections - TORCHES
6. Neurocutaneous syndrome
7. Inborn error of metabolism
8. Postnatal injury eg. Head injury, intracranial bleed, HIE
9. Muscular dystrophy

- Investigation for CP (Refer notes above)


- Investgation for Global Developmental Delay:

1. Thyroid function test


2. Chromosomal study
3. Brain imaging:
• MRI (motor cortex)
• CT scan (malformations, haemorrhage, periventricular leukomalacia)
• Ultrasound (cyst and structural abnormalities
4. TORCH screen including HIV in infants for congenital infection
5. BUSE: high urea level due to liver disorder or inborn error of metabolism à toxic to the brain
6. Urinary metabolic screen (degenerative condition, inborn error of metabolism
7. EEG- seizure, epilepsy
8. EMG, nerve conduction study: muscular dystrophy
9. Intelligence testing is used to help determine if a child has any intellectual impairment, however
intelligence testing a child with movement difficulties does not always give a true result.
- Management:
- Multidisciplinary (Refer notes above)
- Know social support avenues in Malaysia
- Spastic Children Association (SCA)
- Kuala Lumpur Cerebral Palsy Association (KL CPA)

108
Febrile Convulsion/ Seizure

Definition:
Seizure - Clinical event in which there is a sudden disturbance of neurological
function in association with abnormal or excessive neuronal discharge
Epilepsy - Continuing tendency to have seizures (recurrent seizure) without
provoking factors
Febrile - Seizure associated with fever
convulsion - Absence of other causes (eg. metabolic disturbance, trauma) and no
intracranial infections (eg. meningitis, encephalitis)
- Diagnosis of exclusion

Epidemiology:
- Occurs in about 3% of children: 6 months to 6 years of age
- Earlier the age of occurence, the higher risk of recurrence
- Genetic predisposition (10-20% have positive family history including relatives)
Focal seizures:
Clinical features: - Parietal: numbness/tingling
- Have recent infection hx such as URTI, Otitis media, UTI, AGE sensation
- Raised in temperature rapidly - Temporal: deja vu
- Frontal: wave-like sensation in
- Fitsà generalized tonic-clonic seizure
head
- Occipital: visual disturbance/
hallucination

Classification:
Simple (75%) Complex(25%)
- Last for <5 minutes - Last >5 minutes
- NO focal seizures - Focal seizures present
- NO recurrence in 24 hrs - Multiple seizures in 24 hrs (>1 episode)
- NO brain damage - Risk of subsequent epilepsy (30%)
- Generelised tonic-clonic - Intellectual performance may be affected
- Normal development - Residual neurological deficit post ictally eg.
- No encephalopathy Todd`s paralysis*
- No intracranial pathology - Abnormal development
- Usually during 1st day of fever - No encephalopathy
- Usually aged between 6 months - 6 y/o - No intracranial pathology
- Positive family history of febrile convulsion- Usually occurs other than 1st day of fever
- Normally in those aged <6 months or >6
years old
- Family history of epilepsy or epilepsy
syndrome eg. GEFS+**
* Todd`s paralysis: paralysis of the involved limbs after seizure
** GEFS+ (Generalized Epilepsy with Febrile Seizure Plus)
- An unusual epilepsy syndrome. It describes families who have several members from
different generations with epileptic seizures. The epileptic seizures nearly always start after a
family member has had febrile convulsions.

109
Complications:
Epilepsy - Occurs in ~1% of patients
- Risk factors:
- Neurodevelopmental abnormality eg. cerebral palsy
- Complex febrile convulsion
- Family history of epilepsy
- Brief duration between onset of fever and initial convulsion
Recurrence - Recur in ~15% in the same illness
- Risk of recurrence:
- Family history of febrile convulsion
- Age <18 months (early onset)
- Low degree of fever (<40⁰C) during 1st febrile convulsion
- Brief duration (<1 hour) between onset of fever and convulsion

Differential Diagnosis:
Infection - Meningitis/encephalitis
- UTI
Trauma - Brain lesion (in head trauma, intracranial bleed)
Metabolic - Hypoglycemia
- Hypocalcaemia
- Hypomagnesemia
- Hypo/hypernatraemia
- Inborn error of metabolism (IEM)
Others - Poisons/toxins/drugs
- Hypoxic ischaemic insult
- GEFS+
- A group of AD disorder with variable phenotypes
- Disorders are divided into 4 main groups (1,2,3, and SCN2A), each
associated with defect in either α, β, γ subunit. Several genetic defects
are implicated.
- GEFS+ may mimic febrile seizure in the early stage
- Seizure usually extend beyond 6 years old, there may be intercurrent
afebrile seizures & there may be other seizure in addition to the typical
generalized tonic-clonic seizure of febrile seizure.
- Consequently psychomotoe retardation may accompany GEFS+

Investigations:
Blood - FBC (evidence of infection)
- BUSE (hypo/ hypernatraemia)
- Serum calcium & magnesium
- Dextrostix or RBS (hypoglycemia)
- Blood C & S (for evidence of septicaemia)
Urine - U-FEME + C & S (exclude UTI)
LP - Indicated in patients <18 months (subtle S & S)
- TRO meningitis & encephalitis
EEG - Not indicated even for those with multiple recurrence or with complex
febrile convulsions
110
Lumbar Puncture
- Must be done (unless contraindicated)
- Any signs suspicious of intracranial infection
- Prior antibiotic therapy
- Persistent lethargy and not fully interactive 6-8 hrs after the seizure
- Strongly recommended:
- <12 months old
- First complex febrile convulsion
- In district hospital without peadiatrician
- If parents have a problem with bringing the child again to hospital in event of deterioration
at home

Management:
Not all children need to be admitted. The main reasons for admission are:
- TRO intracranial pathology especially infections
- Fear of recurrent fits
- To investigate and treat the cause of fever besides meningitis/encephalitis
- To ally parental anxiety, especially if they are staying far from hospital

Specific Management General Management


- If prolonged seizure > few minutes Management at home
- IV/Rectal diazepam 1. Stay calm, don`t panick
- Manage as status epilepticus 2. Take note of time on onset (duration)
(refer below) 3. Remove dangerous objects around the
patient
4. Clear the airway, wipe away any vomitus or
*International League Against Epilepsy (ILAE) secretion form the mouth
defined status epilepticus more than 20 5. Do not insert any objects into the mouth even
years ago as single epileptic seizure >30 mins if the teeth is clenched
duration or a series of epileptic seizures 6. Do not give any fluids or drugs orally
during which function is not regained btw 7. Lay the child on the left lateral side
ictal events in a 30-min period. BUT, due to 8. Stay near the child until convulsion is over
clinical urgency in treating generalised
and comfort the child if s/he is recovering
convulsive status epilepticus (GCSE), 30-min
9. Rapid sponging, remove the clothes to lower
definition no longer practical or appropriate
in clinical practice. Once seizure have
temperature
continued for more than a few minutes, 10. If second attack, go to hospital
treatment should be initiated.
Management at hospital
Follow step 1-9
11. Give anti-pyretics (eg. PCM 15mg/kg 6 hrs,
ibuprofen)
12. Prevention of recurrence
- Give rectal diazepam 0.5mg/kg (teach
mother as well)

111
Management at ward
13. Put on fit chart
14. Reassess patient and risk of recurrence
15. PCM
16. teach home management
17. Educate parents on monitoring body
temperature and prognosis of febrile seizure
18. Prophylatic anticonvulsant
- Phenobarbitone/sodium valproate
- Indications ( not absolute):
- Severe seizures or high risk of recurrence
- Patient <1 year old
- Patient with risk factors for AFS
- Excessively anxious parents

Status Epilepticus:
Immediate 1. Assess cardiorepiratory function (ABC)
management 2. Oral airway & administer oxygen
3. Establish IV lines, draw blood for glucose, BUSE & anticonvulsant
levels (in treated patients)
4. IV infusion of glucose (50% glucose bolus)
5. IV diazepam ( 0.25-0.5mg/kg) at rate no faster than 2 mg/min
- Rectal diazepam (0.5-0.75 mg/kg) if IV line not established
6. Monitor vital functions
- Correct any metabolic disturbances (eg. glucose, electrolytes)
- Lower body temperature
- Tracheal intubation & assisted ventilation may be necessary
2nd Step IV Phenytoin (20mg/kg) over 20 mins
Management - Investigate possible causes of SE that may require emergency Rx
If seizures NOT IV Phenobarbitone (10-20 mg/kg)
controlled - Monitor BP & RR (esp if pts received diazepam during initial Mx)
Resistant Seizures 1. Further dose of IV Phenobarbital (if patient still fitting)
- May be necessary to exceed usual recommended upper therapeutic
level of 50 mg/mL
- Monitor for respiratory distress
2. Close monitoring
- EEG monitoring
- Closed supervision (specialized nursing & medical personnel)
3. Consider other anticonvulsant
- eg. Paraldehyde, Lignocaine, Sodium valproate
4. IV barbiturate or halothane + neuromascular blockade
- Induce barbiturate coma if the above drugs fail to terminate seizure

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Epilepsy

Definition (ILAE 2014):


- At least two unprovoked seizures occuring >24 hours apart
- One unprovoked seizure & a probability of further seizures similar to the general recurrence
risk (≥60%) after 2 unprovoked seizures, occuring over the next 10 years
- Diagnosis of an epilepsy syndrome
- Considered to be resolved for
- Individuals who had age-dependent epilepsy syndrome but are now past the applicable age
- Those who have remained seizure-free for last 10 years, not on anti-epileptics for last 5 years
- Chronic, group of condition in which recurrent seizures occur spontaneously in the absence of
an acute precipitating condition (unprovoked seizure)
- Epileptic seizure is the clinical manifestation of an abnormal and excessive discharge of a set of
neurons in the brain.
- Epileptic syndrome is a complex of signs and symptoms that define a unique epilepsy
condition. Syndromes are classified on the basis of seizure type(s), clinical context, EEG features
and neuroimaging.
- It is important to differentiate epileptic seizures from paroxysmal non-epileptic events eg.
neonatal sleep myoclonus, breath-holding spells, vasovagal syncope, long Q-T syndrome.

Pathophysiology:
- Instability of neuronal cell membrane (imbalance excitatory & inhibitory neurotransmission) →
Paroxysmal neuronal discharge which produces the clinical seizure (neurological disturbances)

Aetiology:
- Genetic
- Congenital malformation of the brain
- Perinatal complications (brith asphyxia, trauma, intracranial haemorrhage)
- Neurocutaneous syndrome
- CNS infections (meningitis, encephalitis, brain abscess)
- Trauma
- Cerebrovascular accident
- Neoplasm
- Metabolic (hypoglycaemia)
- Any prolonged seizure
* About 50% of epileptic cases, no cause can be found

Classification (Revised ILAE 2011-2013):

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1) Partial - Simple partial (consciousness retained) may involve motor, sensory,
Seizure autonomic, psychic
- involve one - Complex partial (consciousness impaired)
region of - Partial seizure with secondary generation
cortex - `Dyscognitive seizure` is used when difficult to distinguish simple & complex
*According to ILAE 2015 (UpToDate), the terms simple partial, complex partial & secondarily
generalized have been eliminated, since they were difficult to define pragmatically & were often
used incorrectly. Instead, the proposal uses various descriptors of focal seizures to describe an event
more precisely. Examples of preferred descriptors include:
- Without impairment of consciousness or awareness
- Involving subjective sensory or psychic phenomena
- With impairment of consciousness or awareness, or dyscognitive
- Evolving to a bilateral convulsive seizure
.

2) Generalised - Absence
Seizure - Tonic-clonic
- involve both - Myoclonic
hemispheres - Tonic
- Clonic
- Atonic
3) Unclassified - Epileptic/Infantile spasms

Focal epilepsies (Partial seizures)


- Onset in unilateral cerebral hemisphere
- Begins relatively in small group of dysfunctional neurones
Simple partial seizure Complex partial seizure
- No loss of consciousness - Alteration in consciousness
- Clinical features depend on site of seizure arise - Often preceded by an aura
& spread (abnormal unpleasant sensation, smell, visual,
- Frequently involve the motor & sensory auditory, hallucination, fear)
- Motor Sx: Recurrent contraction if muscle in 1 - May assoc with abnormal movement
part of body like hand, leg or face, assoc with (automatism) eg. lip smacking, swallowing,
contralateral motor cortex neuronal discharge pluckering at clothing
- Sensory Sx: Paresthesia or pain in localised area
of body, assoc with sensory cortex neuronal
discharge
.

Frontal lobe seizure - Involves motor cortex


- May lead to clonic movements, which travel proximally same side
(Jacksonian march)
- Asymmetrical tonic seizures can be seen, which may be bizarre &
hyperkinetic, can be mistakenly dismissed as non-epileptic events
Temporal lobe seizure - Strange warning feelings or aura with smell & taste abnormalities &
(Most common) distortions of sound and shape
- Lip smacking, plucking at one`s clothing
- Walking in a non-purposeful manner (automatism) due to spread to pre-
motor cortex
- Deja vu and jamais vu (intense feelings of having been or never having
been, in the same situation before)
- Consciousness can be impaired
- Length of event is longer than a typical absence seizure
Occipital lobe seizure - Causes distortion of vision
Parietal lobe seizure - Causes contralateral dysaethesias (altered sensation)
- Distorted body image
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Generalised epilepsies (Complete seizures)
- Onset in bilateral cerebral hemispheres, without warning
- Always have loss of consciousness
- Symmetrical seizure (bilateral synchronous seizure discharge in EEG)
Absence seizure - Transient loss of consciousness (LOC)
- Abrupt onset and termination
- Occurs usually btw age of 4-9 years, abrupt spontaneously at 12
- Patient stops what he/she is doing & staring blankly ahead or blinking eyes
- Unaccompanied by motor phenomena except some flickering of eyelids
(eyelid myoclonia) & minor alteration in muscle tone
- May be typical (petit mal) or atypical
- Often precipitated by hyperventilation
Myoclonic seizure - Sudden, brief shock-like contraction involving limb & trunk
- Often repetitive
- Jerking movements of limbs, neck or trunk
Tonic seizure - Generalised hypertonia
- May arch the trunk, extend the neck & fall
Tonic-clonic seizure - Most common type
- Rhythmical contraction of muscle groups following tonic phase
- Rigit tonic phase (contraction of all muscle & extension of the limb & trunk,
may fall to the ground causes injury, apnoea & cyanosed followed by clonic)
- Clonic phase:
- Jerking of the limbs
- Irregular breathing (cyanosis persists)
- Saliva accumulates in mouth (drooling of saliva)
- Tongue biting
- Urinary incontinence
- Seizure usually lasts from few seconds to minutes
- Followed by LOW, post-ictal drowsiness or deep sleep up to few hours
Atonic seizure - Often combined with a myoclonic jerk followed by transient hypotonia
(sudden fall to floor/ drop of the head)
- Non-epileptic myoclonic movements are also seen physiologically in
hiccoughs (myoclonus of diaphragm) or during stage II sleep (sleep
myoclonus)

Unclassified epilepsies
Infantile spasms - Usually occurs in infancy (4-6 months)
- Triads of attacks:
- Lightning attack (sudden, severe myoclonic movement of mody, legs bend
(flexor involved more severe than extensor)
- Nodding attack (seizure of throat & neck flexor muscle, during which chin
is fitfully jerked towards breast or head is drawn inwards)
- Salaam or jack-knife attack (flexor spasm with rapid bending of head &
torso forward, simultaneous raising & bending of arms while partially
drawing hands together in front of chest/flailing, similar to ceremonial
greeting)
- Last for several secondas & often occur in multiple burst spasms
- West syndrome (triads of infantile spasms, pathognomonic hypsarrhythmia
EEG pattern & developmental regression)
- Prognosis is poor & intellectual handicap frequently follows

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Investigations:
- Baseline blood & urine test (TRO hypoglycaemia, hypocalcaemia, systemic illness)
- ECG (suspect cardiac dysrhythmia)
- EEG
- Indicated to support the clinical diagnosis of epileptic seizures, classify the epileptic
syndrome, selection of anti-epileptic drug and prognosis
- Helps in localization of seizure foci in intractable epilepsy
- Normal EEG does not rule out epilepsy, epileptiform EEG does not indicate pts had clinical
seizure
- Neuroimaging (preferably MRI) indications:
- Epilepsy occurring in the first year of life, except febrile seizures
- Focal epilepsy except benign rolandic epilepsy
- Developmental delay or regression
- Intractable epilepsy
- Progressive neurological symptoms & signs of raised ICP

Diagnosis:
- Primarily based on a detailed history of characteristics of fits from eyewitnesses
- Any factor which suggest patient is prone to fits
- Neurological examination is essential First Aid Measures during a Seizure (Advise for Parents/
Teachers)
- Differential diagnosis: - Do not panic, remain calm. Note time of onset of the seizure
- Loosen the child`s clothing especially around the neck
- Breath holding attack - Place the child in a left lateral position with head lower than
- Refelx anoxic seizure the body
- Vasovagal syncope - Wipe any vomitus or secretion from the mouth
- Cardiac arrhythmias - Do not insert any object into the mouth even if the teeth are
- Migraine clenched
- Do not give any fluids or drugs orally
- Benign paroxysmal vertigo - Stay near the child until the seizure is over and comfort the
child as he/she is recovering
Management:
A) Principle of anti-epileptic drug therapy for Epilepsy):
- Treatment recommended if ≥ 2 episodes (recurrence risk up to 80%)
- Attempt to classify the seizure type(s) and epileptic syndrome. Monotherapy as far as possible.
- Choose most appropriate drug, increase dose gradually until epilepsy controlled or maximum
dose reached or side effects occur.
- Add on the second drug if first drug failed. Optimise second drug, then try to withdraw first
drug. (alternative monotherapy)
- Rational combination therapy (usually 2 or maximum 3 drugs) eg. combines drugs with
different mechanism of action and consider their spectrum of efficacy, drug interactions &
adverse effects.
- Drug level monitoring is not routinely done (except phenytoin), unless non-compliance,
toxicity or drug interaction is suspected.
- When withdrawal of medication is planned (generally after being seizure free for 2 years),
consideration should be given to epilepsy syndrome, likely prognosis and individual
circumstances before attempting slow withdrawal of medication over 3-6 months (maybe
longer if clonazepam or phenobarbitone). If seizures recur, the last dose reduction is reversed
and medical advice sought.

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B) Selecting antiepileptic drugs according to seizure types:
Seizure type First line Second line
Focal Seizures
Carbamazepine Valproate Lamotrigine,Topiramate, Levetiracetam, Clobazam,
Phenytoin, Phenobarbitone
Generalized Seizures
Tonic-clonic / clonic Valproate Lamotrigine,Topiramate, Clonazepam,
Carbamazepine1, Phenytoin1, Phenobarbitone
Absence Valproate Lamotrigine, Levetiracetam
Atypical absences, Valproate Lamotrigine,Topiramate, Clonazepam, Phenytoin
Atonic, tonic
Myoclonic Valproate Clonazepam Topiramate, Levetiracetam Clobazam, Lamotrigine2,
Phenobarbitone
Infantile Spasm ACTH, Prednisolone, Vigabatrin3 Nitrazepam, Clonazepam, Valproate,Topiramate
Footnote:
1, May aggravate myoclonus/absence seizure in Idiopathic Generalised Epilepsy.
2, May cause seizure aggravation in Dravet syndrome and JME.
3, Especially for patients with Tuberous Sclerosis.

C) Antiepileptic drugs that aggravate selected seizure types:


Anti-epileptic drug Worsened seizure type
Phenobarbitone Absence seizures
Clonazepam Causes Tonic status in Lennox-Gastaut syndrome
Carbamazepine Absence, Myoclonic, Generalised tonic-clonic seizures
Lamotrigine Dravet syndrome, Myoclonic seizures in Juvenile Myoclonic Epilepsy
Phenytoin Absence, Myoclonic seizures
Vigabatrin Myoclonic,Absence seizures

D) Side effects & serious toxicity of anti-epileptic drugs:


Anti-epileptic drug Common side effects Serious toxicity
Carbamazepine Drowsiness, dizziness, ataxia, diplopia, rashes Steven-Johnson syndrome1,
Agranulocytosis
Clobazam2 Clonazepam Drowsiness, hypotonia, salivary and bronchial -
hypersecretion, hyperactivity and aggression
Lamotrigine Dizziness, somnolence, insomnia, rash Steven-Johnson syndrome
Phenobarbitone Somnolence, asthenia, dizziness, irritability, -
behavioural change
Phenytoin Behavioural disturbance, cognitive dysfunction, -
drowsiness, ataxia, rash
Sodium valproate Ataxia, diplopia, dizziness, sedation, hirsutism, gum -
hypertrophy megaloblastic anemia
Topiramate Nausea, epigastric pain, tremor, alopecia, weight gain, Hepatic toxicity (<2 yrs age),
hair loss, thrombocytopaenia pancreatitis,
Encephalopathy
Vigabatrin Drowsiness, dizziness, mood changes, weight gain Peripheral visual field
constriction (tunnel vision)
Footnote
1, Steven-Johnson syndrome occurs more frequently in Chinese and Malay children who carry the HLA-B*1502 allele.
2, Clobazam is less sedative than clonazepam

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E) In patients with `Intractable Epilepsy`, re-evaluate:
- Is it a seizure or a non-epileptic event?
- Antiepileptic drug dose not optimised
- Poor compliance to antiepileptic drug.
- Wrong classification of epilepsy syndrome, thus wrong choice of antiepileptic drug
- Antiepileptic drug aggravating seizures
- Lesional epilepsy, hence a potential epilepsy surgery candidate
- Progressive epilepsy or neurodegenerative disorder
F) When to refer to a Paediatric Neurologist?
- Refer immediately (to contact paediatric neurologist)
- Behavioural or developmental regression
- Infantile spasms.
- Refer
- Poor seizure control despite monotherapy with 2 different antiepileptic medications
- Difficult to control epilepsies beginning in the first two years of life
- Structural lesion on neuroimaging
G) Advice for Parents
- Educate and counsel on epilepsy
- Emphasize compliance if on an antiepileptic drug
- Don`t stop the medication by themselves. This may precipitate breakthrough seizures
- In photosensitive seizures: watch TV in brightly lit room. Avoid sleep deprivation
- Use a shower with bathroom door unlocked
- No cycling in traffic, climbing sports or swimming alone
- Know emergency treatment for seizure
- Inform teachers and school about the condition

Classification of epilepsies and epileptic syndromes (Adapted from ILAE 2010)


Neonatal Childhood Adolescent - Adult
Benign familial neonatal epilepsy Febrile seizure plus (FS+) Juvenile absence epilepsy (JAE)
Early myoclonic encephalopathy Epilepsy with myoclonic-atonic Juvenile myoclonic epilepsy (JME)
seizures
Ohtahara syndrome Panayiotopoulos syndrome Epilepsy with GTC seizures alone
Benign rolandic epilepsy (BECTS) Progressive myoclonic epilepsies
(PME)
Infancy Autosomal-dominant nocturnal FLE Familial focal epilepsies
West syndrome Late onset childhood occipital
epilepsy
Myoclonic epilepsy in infancy Epilepsy with myoclonic absences Others
Benign infantile epilepsy Lennox-Gastaut syndrome Mesial TLE with hippocampal
sclerosis
Benign familial infantile epilepsy Epilepsy with continuous spike-wave Gelastic seizures with hypothalamic
during sleep (CSWS) hamartoma
Dravet syndrome Landau-Kleffner syndrome (LKS) Hemiconvulsion-hemiplegia-
epilepsy
Childhood absence epilepsy (CAE) Rasmussen syndrome
Reflex epilepsies
* Epilepsies (generalized or focal), due to: (If unable to classify into the above)
- Structural / metabolic causes
- Genetic causes
- Unknown cause.
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Neural Tube Defects (NTDs)

Definition:
Failure of normal fusion of the neural plate to form neural tube during the first 28 days following
conception.

Epidemiology:
- Based on Malaysian National Neonatal Registry 2013, prevalence of NTD was 0.42 per 1000
livebirths, highest among indigenous people of Sarawak, lowest among Chinese descent
- Most common type of NTDs: Anencephaly (0.19/1000), Spina bifida (0.11/1000), Encephalocele
(0.07/1000)
- Associate with high mortlity, long-term monitoring of NTD with folic fortification is
recommended.

Overview:
Brain

Spinal Cord

Craniorachischisis totalis - Total failure of fusion neural plate


- Most cases aborted in early pregnancy
Anencephaly - Failure of anteior neural tube closure causing failure of the
development of forebrain, upper brain stems and cranium
- Affected infants are stillborn or die shortly after birth
- TOP can be performed if detected via antenatal USS screening
Encephalocele - Extension of brain & meninges through a midline skull defect
- Often associate with underlying cerebral malformation
- Can be corrected surgically
Iniencephaly - Defect to occipital bone, spina bifida of cervical vertebrae &
retroflexion (backward bending) of head of cervical spine
- Rare occurrence, stillbirth is most common outcome, livebirth
possible but death occurs almost invariably after birth
Cranial Meningocele - Protrusion of meningeal sac via a skull defect with normal brain

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Spinal Meningocele - Protrusion of meningeal sac without any neural element via a
spinal defect
- Neurological symptoms & signs are absent
- Often present as a swollen fluctuant mass covered with a full
thickness of skin with positive transilluminatoin test
- Can be repaired surgically & have good prognosis
Spinal Myelomeningocele - Failure of posterior neural tube closure causing protrusion of
meninges with neural tissue & CSF
- Can be presented with wide range of problems (refer below)
- Closure of spinal defects should be done within 1st week of life
- Severely affected children may develop handicap after active Tx
- Subsequent care is best managed by multidisciplinary teams with
the aim of improving their quality of life
Spinal bifida occulta - Failure of closure of vertebral arch occurs in ≥5% population
- Mostly asymptomatic (incidental finding on X-ray)
- Commonly in lumbosacral region with overlying skin changes
(tuft of hair, lipoma, birth mark or dermal sinus)
- Whenever associated with neurologic involvement, it is termed
occult/closed spinal dysraphism
Occult/closed spinal dysraphism - Spina bifida occulta with distortion of spinal cord or spinal roots
by fibrous bands and adhesions, intraspinal lipoma, dermoid or
epidermoid cyst, fibrolipoma, tethered cord/ diastematomyelia
(most common)
- With growth, it may cause neurological deficits of bladder, bowel
function & lower limbs
- Neurosurgical relief of tethering is usually indicated

Problem in Myelomeningocele:
Problem Management
Paralysis of legs (variable) - Physiotherapy (prevent joint contracture &
- Depends on level of lesion (muscle innervated by strengthen paralysed muscles)
nerve below lesion will be paralysed) - Walking aids & wheelchair (permit mobility)
Dislocation of hip & talipes equinovarus (Imbalance)
- Due to partial denervation of LL
Sensory loss (anaesthesia) - Skin care
- Dermtomes below level of lesion - Prevent development of skin lesion & ulcer
- May lead to pressure sores
Neuropathic bladder (bladder denervation) - Indwelling catheter or intermittent
- Can lead to hydronephrosis & UTI, renal failure, catheterisation
reflux nephropathy - Medication (Oxybutinin & Ephedrine)
- May improve bladder function & dribbling
- Regular urine check for UTI
- Prophylactic antibiotics can be given
- Monitor hydronephrosis & renal failure (USS)
Neuropathic bowel (bowel denervation) - Regular toileting & suppositories
- Laxatives
Scoliosis - Surgical repair

Hydrocephalus from Arnold-Chiari Malformation - Ventricular shunting


- Herniation of cerebellar tonsils through foramen
magnum leading to disruption of CSF flow

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Spina bifida Short Case (Template)
- General planning for this case:
- Demonstrate the level of lesion
- Functional assessment (ability to walk)
- Look for associated abnormalities or complications (hydronephrosis, hydrocephalus)
Q: `This boy has spina bifida. Would you please assess his/her function above the level of lesion?`

- Child s posture & spontaenous movement is valuable to localise level of lesion:


1. Hip flexion corresponds to L1 and L2, so is affected in high lesions.
2. Lesions above L1 cause total paraplegia, as hip flexion is absent. Thus, in thoracic lesions, the lower
limbs are flaccid, in a `frog leg` position of external rotation, with some degree of passive abduction
and flexion at the hips, and the knees slightly flexed, the ankles plantar flexed.
3. Lesions in the high lumbar zone cause the child to lie in a position of flexion & adduction at the hips.
4. Lesions with L3 preserved allow an infant to exhibit some kicking movements when upset, with
some knee flexion and extension.
5. Lesions in the low lumbar zone result in a position of hip flexion and adduction, good knee flexion
and extension, and ankle dorsiflexion, due to unopposed action of the tibialis anterior (L5).
6. Hip extension corresponds to L5, S1 and S2, and so is affected in all but the lower sacral lesions.
7. Lesions at S3 or below completely spare lower limb sensory and motor function, but cause paralysis
of bladder and anal sphincters, and `saddle anaesthesia`.

Physical Examination
Introduce self - Interact with child, gain impression of development
General Inspection - Alertness
- Cry (high-pitched with ACM)
- Nasogastric tube (severe ACM)
- Respiratory distress
- Hoarseness of voice (severe ACM)
- Posture (deformity eg. TEV, dislocated hips)
- Muscle bulk (LL vs UL)
- Movement (LL vs UL, Ataxia - ACM)
- Head (Size, Shunts, Eye signs)
- Skin
Back - Lesion
- Site (closure scar if have, describe)
- Spinal deformity (scoliosis, kyphosis)
- Scars (eg. fixation rod)
Lower limbs (LL) - Inspect, Palpate, Tone, Power, Reflexes, Joint movement, Sensation
Abdominal & pressure - Inspect (scars eg. VP shunt; distention-lax muscles, ileal conduit,
areas patulous
anus, dribbling of urine, Tanner staging-precocity, Pressure sores
- Palpate (kidney: hydronephrosis)
- Percuss (bladder: urinary retention)
- Check (Abdominal reflexes, Anal wnk, Anal tone)
- Urinalysis (detect CRF, shunt nephritis, UTI)
Head - Inspect (Size, Shape eg. frontal prominence, Signs of hydrocephalus:
scalp vein prominence, shiny skin, sun-setting eyes, shunt scars)
- Measure head circumference & request progressive percentiles
- Palpate (sitting up): Fontanelles, Sutures, Shunt (trace tubing)
Eyes - Inspect (Nystagmus: severe ACM, Squint eg. with ACM)
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- Visual acuity
- External ocular movement (CN6 palsy, Impaired upward gaze: Parinaud`s
syndrome with hydrocephalus)
- Fundi (Papilloedema: raised ICP, Optic atrophy: long-standing raised ICP)
Hearing & bulbar function - Assess hearing
- Check lower CN 9,10,11,12
- Suck & swallow reflexes
- Gag reflex (if cannot swallow)
- Tongue atrophy
Upper limbs (UL) Full examination for signs of syringomyelia
Blood pressure Hypertension (CRF)
Chest Full examination of praecordium & lung fields for signs of heart failure dt:
- Hypertension (CRF)
- Cor pulmonale (kyphoscoliosis)
Functional/developmental - Assess ADL in older children
assessment - Perform developmental assessment in infants
Details of possible findings on Spina Bifida examination
Respiratory signs - Stridor (severe ACM)
- Apnoea (severe ACM)
- Tachypnoea (aspiration pneumonia, heart failure)
Skin - Pressure sores
- Scars (eg. VP shunts, tendon releases)
Growth parameters - Head circumference (increased in hydrocephalus)
- Height (usually decreased)
- Arm span (use instead of height, may be normal for age)
- Weight (obese for height, not for arm span)
Lower Limbs - Inspection
- Muscle bulk wasting
- Joint deformity (eg. dsislocated hips, talipes)
- Contractures
- Scars (eg. tendon release, transfers or osteotomies)
- Spontaneous movement
- Palpation (muscle bulk, each muscle compartment)
- Check tone, power, reflexes (including with reinforcement)
- Joint movement
- Hip (eg. fixed flexion deformity, check for dislocation last)
- Knee (eg. fixed hyperextension)
- Ankle (eg. fixed dorsiflexion)
- Check hip for dislocation
- Sensation: demonstrate sensory level (may use a new pin in infants, full
examination in older children)

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Hydrocephalus

Definition:
Obstruction to the flow of CSF → leading to dilatation of the ventricular system proximal to the
site of obstruction.

Aetiology:
- Can be either due to;
- Non-communicating (Obstructive hydrocephalus)
- Obstruction within the ventricular system or aqueduct → Interrupt with CSF flow
- Communicating
- Obstruction at the arachnoid villi → Failure of CSF reabsorption
* Rarely due to overproduction of CSF (choroid plexus papilloma)

Non-communicating Communicating
- Congenital malformation - Subarachnoid haemorrhage (SAH)
- Aqueduct malformation/stenosis - Decreased CSF reabsorption
- Danky-Walker Syndrome - Meningitis: Pneumococcal, Tuberculous
- Atresia of the outflow foramina of the 4th (follow by adhesion & obstruction to the flow
ventricle of CSF)
- Arnold-Chiari malformation - Intrauterine infection (Toxoplasmosis, CMV)
(medulla oblongate & cerebellum protrude - Choroid plexus papilloma (rare)
into the spinal canal) - Increased CSF production
- Posterior fossa neoplasm
- Medulloblastoma
- Cystic cerebellar astrocytomas
- Vascular malformation
- Intraventricular haemorrhage (preterm)
(Blood in the CSF may give rise to adhesion
which obstruct the flow of CSF)
*Some can cause both non-communicating and communicating hydrocephalus

Clinical features:
- Depend on 3 factors:
- Whether the fontanelle & sutures have fused
- Whether the obstruction is acute vs chronic
- Underlying pathology cause

- Generally in child < 2 years old:


- Head circumference is disproportionately large or rate of growth is excessive
- Cranial sutures are separated (usually closes by 12-18 months)
- Anterior fontanelle is bulge, tense
- Distended scalp vein
- Eyes deviated to downward gaze if left untreated (setting-sun sign)

123
- S & S of increased ICP (usually in older chidren > 2 years old:
Symptoms Signs
- Headache (worse on lying down, cough) - Bradycardia *Cushing`s reflex
- Irritable, non-stop crying - Hypertension
- Morning vomiting - Papilledema (if present for long time)
- Changes in personality or mood & school - Diplopia (CN 6 paresis)
performance

Complications:
- Seizure
- Failure to thrive (FTT)
- Mental retardation - Cerebral atrophy
- Neurological deficit
- Cranial nerve palsy
- Cerebellar ataxia
- Affected limb

Investigation:
- Radiology
- Cranial USS (Look for evidence of ventricular dilatation)
- CT/MRI
- Ophthalmoscopy - Look for evidence of papilledema
- Centile charts - Head circumference should be monitored over time

Diagnosis:
- Usually can be diagnosed by history & clinical examination
- Can be diagnose antenatally by USS screening or routine cranial USS in preterm

Management:
- Head circumference should be monitoring over time on centile charts
- Aims of intervention are:
- Treat to the cause of hydrocephalus
- Symptomatic relief
- Minimise neurological damage
- Mainstay of management is ventricular shunt
(either ventriculo-atrial or ventriculo-peritoneal)
- Endoscopy & ventriculostomy can now be performed alternatively
- Complications:
- Shunt malfunction
- Infection (particularly with coagulase-negative Staphylococcus)
- Overdrainage of fluid

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Neurocutaneous Disorders

Introduction:
- Syndromes involving abnormalities of skins and nervous systems (which have common
ectodermal origin)
- Include Neurofibromatosis Type 1, Tuberous sclerosis & Sturge-Weber syndrome

A) NEUROFIBROMATOSIS

Neurofibromatosis 1 (NF-1) or von Recklinghausen disease


- Introduction:
- Autosomal dominant disease
-1/3 are from new mutation
- Affecting 1 in 4000 live births
- Criteria for diagnosis: (≥ 2 criteria)
- ≥ Six cafe-au-lait spots >5mm in size pre-puberty OR >15mm post-puberty
- > One neurofibroma (unsightly firm nodule overgrowth of any nerve)
- Axillary freckling
- Optic glioma (which may cause visual impairment)
- One Lisch nodule (a harmatoma of the iris seen on slit lamp)
- Bony lesions frm sphenoid dysplasia which can cause eye protusion
- 1st degree relative with NF-1

Neurofibromatosis 2 (NF-2):
- Central neurofibromatosis
- Due to mutation on different gene on chromosome 22
- Much rarer form (affecting1 in 40000 live births)
- Characteristic presentation:
- Bilateral acoustic neuromata (may cause deafness)
- Other presentations: Cerebellopontine angle syndrome with a facial (VII) nerve
paresis & cerebellar ataxia

*Most people carry no features other than the cutaneous stigmata

Both NF1 and NF 2 are associated with:


- Endocrinological disorders: MENS (Multiple Endocrine Neoplasia syndrome)
- Phaeochromocytoma
- Pulmonary stenosis
- Renal artery stenosis (Hypertension)
- Gliomatous changes in CNS
- Sarcomatous changes (rare)
- Learning disabilities
- Bony complications (vertebral dysplasia, mild scoliosis, pseudoarthroses, overgrowth)
- Leukaemia (juvenile chronic myelogenous leukaemia & myelodysplastic syndrome)

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B) TUBEROUS SCLEROSIS

Introduction:
- Autosomal dominant inherited disorders
- 70% cases represent new mutation
- Affecting 1 in 7000 live births

Cutaneous features:
- Depigmented ash leaf shaped patches: Fluoresce under Wood`s light
- Roughened patches (shagreen patches): usually over lumbar spine
- Adenoma sebaceum (angiofibromata): In butterfly distribution before 3 years old
* Most people carry no features other than the cutaneous stigmata

Neurological features:
- Infantile spasm
- Developmental delay
- Epilepsy (often focal)
- Intellectual impairment (learning difficulties with autistic features)

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Other features:
- Subungual fibromata(fibromata beneath the nails)
- Phakomata (dense white area on the retina)
- Rhabdomyomata of the heart
- Polycystic kidneys
- Gliomatous change in CNS

C) STURGE-WEBER SYNDROME
- Sporadic disorder characteristics by;
- Unilateral facial naevus lesion (Port-wine stain) in trigeminal nerve distribution
- Leptomeningeal angiomatosis
- There are abnormal blood vessels over the brain surface: may be associate with seizures,
hemiplegia and learning difficulties
- CT brain
- Unilateral intracranial calcification with a double contour `rail-road ` subcortical calcification
- Associated parenchymal volume loss due to cortical atrophy
- Evident enlargement of calvarial and regional sinus

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Muscular Dystrophy

A) DUCHENNE`S MUSCULAR DYSTROPHY:

Epidemiology:
- Commonest cause of muscular dystrophy
- Incidence is about 1 in 4000 male infants (UK)

Cytogenetic:
- Inherited as an X-linked recessive disorder (thus only in males)
- Deletion of chromosomal material on the short arm of X-chromosome (Xp21 site)
- Known to code a protein called dystrophin to maintain the integrity of muscle cell wall
- Deficiency of dystrophin causes
- Influx of Ca2+
- Breakdown of calcium-calmodulin complex
- Excess free radicals being released
- One-third are new mutations

Clinical Features:
- Average age of diagnosis is 5.5 years
Symptoms Signs
Early childhood - Gower`s sign
- Delayed walking - Difficulty in getting up from sitting position
- Difficulty in getting up from sitting position due to weak proximal muscles
- Difficulty in climbing - Waddling gait
- Tendency to falling - Tendency to walk on toes
- Weak anterior tibial muscle
Early School Years - Marked lumbar lordosis
- Slower & clumsy than their peers - Scoliosis
(Learning difficulties) - Pseudo-hypertrophy (calf muscle)
- Non-ambulant by the age of 10-14 years - Selective atrophy
(Atrophy & muscle weakness) - Brachioradialis
- Sternal head of pectoralis major
- Depressed reflexes (except ankle jerk)

Investigation:

Blood - Markedly raised serum creatine phosphokinase (CPK)


EMG - Low voltage interference pattern
- Polyphasia of motor units
- Decreased voltage & duration of motor unit activity
Muscle biopsy - Wide & random variation of cross-sectional diameter of fibers
- Central or internal position of sarcolemmal nuclei
- Splitting of small groups of fibers with replacement by fat &
connective tissue

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Complication:
- Scoliosis (common complication)
- Inability to walk (Paralysis)
- Deaths (usually in the late teens or early 20s)
- Respiratory failure (Nocturnal hypoxia due to weak intercostal muscles)
- Cardiomyopathy

Management:
Conservative Operative
- Prevention of contracture - Lengthening of Achilles tendon
- Passive stretching - Facilitate ambulation
- Provision of night splints - Management of scoliosis
- Maintenance of muscle power by - Insertion of metal rod into the spine
appropriate muscle exercise
- Prolonged mobility
- Delays the onset of scoliosis
- Orthoses
- Prolongation of walking
- Management of scoliosis
- Maintaining good sitting posture
- Trunchal brace, moulded seat
- Respiratory aids
- Indicated when weakness of intercostal
- Muscles develop
- Provision of special schooling
- Emotional support

B) BECKER`S MUSCULAR DYSTROPHY


Introduction:
- Milder form of muscular dystrophies
- Production of some functional dystrophin

Clinical features:
- Similar to DMD but clinically the disease progresses more slowly
- Average age of onset = 11 years old
- Inability to walk in late 20s
- Deaths in early 40s

C) CONGENITAL MUSCULAR DYSTROPHY


- Heterogenous group disorder (AR inheritance)
- Clinical features: Muscle weakness at birth or early infancy
- Investigation
Muscle biopsy - Dystrophic features with reduction of merosin

Neuroimaging - Evidence of central nervous system involvement

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PART IV

CARDIOLOGY
Congenital Heart Disease

Introduction:
- Commonest congenital malformation seen in children, prevalence of 8-10/1000 live birth.
- Most common type of heart defect is VSD.
- About 95% of babies born with a non-critical CHD are expected to survive to 18 years of age.
- About 69% of babies born with critical CHDs are expected to survive to 18 years of age. [CDC 2012]
- In 2006, a study on under five deaths in Malaysia had showed that 10% mortality was directly
related to CHD. [MyCDHR]
- Most structural defects are now diagnosed non-invasively via echocardiography.
- About 10-15% have complex lesions with more than one cardiac abnormality.
- About 10-15% also have a non-cardiac abnormality.

Aetiology:
Cardiac abnormalities Frequency
Maternal disorders
- Rubella infection - PDA, Peripheral PS 30-35 %
- SLE - Complete heart block 35 %
- GDM/ DM - Increased in overall incidence 2%

Maternal drugs
- Warfarin therapy - PS, PDA 5%
- Fetal alcohol syndrome - ASD, VSD, TOF 25 %

Chromosomal abnormalities
- Down syndrome (Trisomy 21) - AVSD, VSD, PDA, ASD, TOF 30 %
- Turner`s syndrome (45 XO) - AS, COA 15 %
- Chromosome 22q11, 2 deletion - Aortic arch abnormalities, TOF
- William`s syndrome - Supravalvular AS, Peripheral PS
(chromosome 7 microdeletion)

Common Congenital Heart Diseases:


Acyanotic Cyanotic

- With left to right shunt (Shunt lesions) Tetralogy of Fallot 6%


Ventricular septal defect 32 % Transposition of great artery 5%
Patent ductus arteriosus 12 % Tricuspid atresia 4%
Atrial septal defect 5% Hypoplastic left heart syndrome 3%
AVSD (complete) 2%
- Without left to right shunt (Non-shunt lesions) Total anomalous pulmonary venous 1%
Pulmonary stenosis 7% connection (TAPVC)
Aortic stenosis 5% Truncus arteriosus 1%
Coarctation of aorta 5% Eisenmenger syndrome -
Double-outlet RV with PS
Critical pulmonary stenosis (PS) <1 %
Ebstein`s anomaly of tricuspid valve

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Congenital heart defect may be presented as/via:
- Antenatal & postnatal diagnosis
- Heart murmur
- Cyanosis
- Heart failure

1) Antenatal diagnosis - Detailed ultrasound scan done at the end of first trimester
Postnatal diagnosis - Routine echocardiogram done on high-risk children:
- With Down syndrome
- Siblings with congenital heart disease
- Mother with congenital heart disease
2) Heart murmur - Murmurs from cardiac defect have to be differentiated from
innocent murmurs
- 2 main types:
- Ejection murmurs (from the outflow tracts)
- Venous hum (from head & neck veins)
- Characteristics of an innocent murmurs:
- Soft, left Sternal edge, Small area, Systolic, normal heart Sound,
aSymptomatic patient (6S)
3) Cyanosis - Peripheral cyanosis (blueness of hands & feet due to poor perfusion)
- Central cyanosis (concentration of reduced Hb >5g/dl in capillary blood
or >3g/dl in arterial blood, less pronounced if the child is anemic)
- Congenital heart disease which cause neonatal cyanosis:
Reduced pulmonary Tetralogy of Fallot
blood flow Tricuspid atresia
(Obtructed) Pulmonary atresia
Abnormal mixing Transposition of great artery (TGA)
(Discordant arterial Hypoplastic left heart syndrome
connection) AVSD (complete)
Total anomalous pulmonary venous drainage
- Diagnosis can be confirmed by HYPEROXIA (nitrogen wash) test
- Hypoxaemia caused by cardiac defects not corrected by increasing
inspired fraction of inspired oxygen (FiO2)
- Child with FiO2 100%, right radial arterial PaO2 <150mmHg suggests
cyanotic CHDs.
- Most infants with cyanotic heart disease in first few days of life are duct-
dependant. Thus, maintenance of ductal patency with IV Prostaglandin
(Prostin) is the key to early survival of these children.

4) Heart failure - Spectrum of clinical syndrome (presents in first 1-2 months)


Symptoms Signs
- Breathlessness - Tachycardia
- Sweating - Tachypnoea
- Poor feeding - Hepatomegaly
- Recurrent chest infection - Cardiomegaly
- Failure to thrive (FTT) - Gallop rhythm, heart murmur
- Pedal oedema, and lung
crepitations are uncommon

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- Causes of heart failure in:
Neonates Infants
- Usually due to obstruction to - Usually due to left to right
the left ventricle (duct- shunts
dependant) - Large VSD, AVSD, large PDA
- Hypoplastic left heart, critical
aortic stenosis, severe
coarctation

Investigation:
- Chest X Ray
A normal CXR and ECG does not exclude CHD
- ECG
- Echocardiography ( look at heart structure ) + Doppler ( look at the flow )
- Cardiac catheterisation mainly used for hemodynamic measurements and intervention

Chest X-Ray - Heart size


- Cardiomegaly (PDA, ASD, VSD, PS etc)
- Normal (CoA)

- Heart shape and position


- Boot-shaped (TOF)
- Box-shaped (Ebstein anomaly)
- Snow man appearance (TAPVC)
- Egg-on-string/ Egg-on-a-string sign (TGA)
- Water bottle sign (Pericardial effusion)
- Dextrocardia

- Pulmonary vasculature
- Plethoric: TGA, TAPVC, Truncus arteriosus
- Oligaemic: TOF, Tricuspid atresia

ECG - RV dominance is normal in neonates, and it is gradually replaced by LV dominance


in later childhood
- Features of RV dominance:
- Right axis deviation
- Large rightward forces : Tall R waves in avR, V1, V2 and deep S waves in I, V5, V6
- Inverted T wave in V1 in infants and small children, except in the first 3 days of life
- The heart rate is faster than in adults
- PR interval, QRS duration, QT interval are shorter than in adults
- Voltage criterias are also different to determine ventricular hypertrophy

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Acyanotic Congenital Heart Disease

A) With left to right shunt

1) Ventricular Septal Defect (VSD)


- Most common (30% of all CHDs)
- 2 main types:
- Perimembranous (adjacent to tricuspid
valve)
- Muscular (completely surrounded by
muscle)
- Clinical features depends on the size of the
left to right shunt across the VSD
- Large defect (same size or larger than aortic
valve)
- Small defect (smaller than aortic valve)

Clinical features:
Symptoms Signs
- Small VSD (Asymptomatic) - Small VSD
- Large VSD - Loud PSM at left sternal edge
- Heart failure - Thrill at Left sternal edge
- FTT especially in 2nd to 3rd month of life - Large VSD
- Recurrent chest infections - Soft PSM at left sternal edge/ No murmur
- Poor feeding - Loud P2 with pulmonary hypertension
- Diaphoresis - Cardinal signs of heart failure:
- Dyspnea - Tachycardia
- Tachypnoea
- Hepatomegaly
- Cardiomegaly

Investigations:
Chest X Ray - Small VSD (Normal)
- Large VSD
- Cardiomegaly
- Enlarged pulmonary arteries
- Plethoric lung fields
- Pulmonary oedema (may present)

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ECG - Small VSD (Normal)
- Large VSD
- LV Hypertrophy/ biventricular hypertrophy
- Signs of pulmonary hypertension (upright T wave)
Echocardiography - Demonstrates anatomy of defect in
heart
- Assess its haemodynamic effects
using Doppler
- Pulmonary hypertension in large
defects

Management:
Small VSD Large VSD
- Advise subacute bacterial endocarditis - Medical
(SBE) prophylaxis - Control heart failure
- Surgery (indicated if) - Oxygen therapy
- The child has an episode of infective - Fluid restriction, nasogastric feeding if
endocarditis (IE) acutely unwell
- There is any sign of progression to - Drugs ( furosemide, spironolactone, thiazide,
pulmonary hypertension ACE inhibitor )
- Prolapsed aortic valve - Subacute bacterial endocarditis prophylaxis
- Surgical
- Indications: severe symptoms with failure to
thrive; pulmonary hypertension with possibly
progression to pulmonary vascular disease;
VSD with PS/AR
- Approaches:
- Transcatheter closure (Amplatzer occluder)
- Dacron or PTFE (Gore-Tex or Impra) patch
- Pulmonary artery banding(↓pulmonary HPT)
Complications:
- Aortic regurgitation
- Infective endocarditis
- Eisenmenger`s syndrome (R>L shunt)
- Infundibular stenosis
- Pulmonary Hypertension
Eisenmenger syndrome
- Occurs when there is cyanosis due to R > L shunting as a result of increased pulmonary blood flow,
pulmonary hypertension, right ventricular hypertrophy and pulmonary vascular disease.
- Complications:
- Hyperviscosity secondary to polycythaemia (headache, dizziness, visual disuturbance)
- Haemoptysis due to pulmonary infarct/ rupture of pulmonary arterioles
- Cerebral infarct due to embolism/ venous thrombosis
- Congestive cardiac failure (CCF)

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2) Atrial Septal Defect (ASD)
- 4 types: (2 major)
Ostium Secundum (80%, most common)
- Deficiency of the foramen ovale and
surrounding
Ostium Primum
- Deficiency of the atrioventricular septum and
is associated with abnormal atrioventricular
valves
- Inter-atrial communication between atrial
septum and AV valves
Sinus venosus
- Occurs at SVC and RA junction, drainage of
pulmonary vein into RA instead of LA
Coronary sinus (Rarest)
- Located within coronary sinus, passes behind
LA.

Clinical features:
Symptoms Signs
- Mostly asymptomatic - Fixed split S2 (stroke volume equal in both
- Recurrent chest infections inspiration & expiration)
- Heart failure - Ejection Systolic Murmur at upper left sternal
- Arrhythmias in adult (4th decades onwards) edge (↑flow via pulmonary valve)
- Paradoxical embolus (when straining, it can - Apical pansystolic murmur from AV valves
cause clot to go from right to left causing regurgitation (ASD primum)
stroke ) - Loud P2

Investigation:
CXR Echocardiography Echocardiography
- Cardiomegaly ± pulmonary - Right axis deviation - For haemodynamic
plethora - Partial/complete RBBB measurements and assess ASD
- RV hypertrophy size
(sometimes)

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Management:
- Nearly all ASDs require closure
- Surgical
- Transcatheter
- Usually done at 4th or 5th year of life, earlier if symptomatic

Complications:
- Eisenmenger`s syndrome
- Paradoxical embolism (rare)

136
3) Patent Ductus Arteriosus (PDA)
- Ductus arteriosus connects pulmonary
artery to the descending aorta. it usually
closes shortly after birth with decrease
in prostaglandin in blood

- Failure to close frequently occurs in


preterm neonates

- In other children, it is thought to be due


to a defect in the constrictor muscle of
the duct.

- Blood flow is from the aorta to the


pulmonary artery ( i.e left to right shunt)
following fall in the pulmonary vascular
resistance after birth.

Clinical features:
Symptoms Signs
- Asymptomatic in small PDA - Collapsing pulse (wide pulse pressure)
- Symptoms of heart failure in large PDA - Continuous murmur, beneath the left clavicle
- In preterm infants, the murmur may be soft and
systolic - usually presents with a collapsing pulse
and failure to wean off the ventilator (wet lung)

Investigations:
CXR & ECG Echocardiography Cardiac catheterisation
- Depends on the size of PDA - Evaluates heart structure & - For haemodynamic
If large, CXR & ECG may show function, assess blood flow measurements and closure
findings similar to large VSD pattern, PDA opening size of PDA (therapeutic)

Management:
Conservative Operative
- Fluid restriction - Surgical ligation
- Pharmacological - Transvenous occlusions with a coil device
- Indomethacin (PG synthase inhibitor) * Depending on symptom severity, PDA size &
- Diuretics (if heart failure) body weight
* In asymptomatic PDA, closure is recommended to eliminate risk of endocarditis.
137
B) Without left to right shunt

1) Pulmonary Stenosis and Aortic Stenosis


Pulmonary Stenosis Aortic Stenosis

Symptoms: Symptoms:
- Usually asymptomatic - Depends on severity:
- A small number of neonates with critical PS - Mild à asymptomatic
have a duct-dependant pulmonary - Critical à severe heart failure/duct-
circulation in the first few days of life. dependant circulation in neonatal period,
reduced exercise tolerance, chest pain on
exertion & syncope

Signs: Signs:
- Ejection systolic murmur at pulmonary area - Small volume plateau pulse
(upper left sternal edge) radiating to the back - Ejection systolic murmur at aortic area
- Thrill at upper left sternal edge (upper right sternal edge) radiating to the
- Ejection click neck
- Loud P2 - Suprasternal/ carotid thrill
Investigation: Investigation:
- CXR à Post stenotic dilatation of pulmonary - CXR à Post stenotic dilatation of
artery ascending aorta
- ECG à RV hypertrophy (upright T wave) - ECG à LV hypertrophy
- Echocardiogram (Tall R in V5,V6; Deep S in V1,V2)
- Echocardiogram
Management: Management:
- Transcatheter pulmonary valvuloplasty - Surgical or balloon valvotomy
(balloon dilatation) - Aortic valve replacement
* Symptomatic children with high resting pressure gradient (>64mmHg) across the pulmonary and
aortic valve are indicated for intervention

138
2) Coarctation of Aorta
Pre-ductal Post-ductal

Presents in infancy as: Presents in older children and adult as:


- CHF - No differential cyanosis is seen
- Differential cyanosis at extremities - Hypertension at upper extremities
- Femoral pulses are weaker than those of the - Blood pressure is low and pulses are weak
upper extremities in lower extremities
- Occurs before the patent ductus arteriosus - Notching of the ribs due to collaterals (seen
- Asynchronous radial pulse in CXR)
- Intermittent claudication à arterial
insufficiency
- Synchronous radial pulse

Clinical features:
Symptoms Signs
- Depends on severity: - Weak of absent peripheral pulses
a) Mild: - Radiofemoral delay (bypass via collateral vessels)
- Heart failure (usually presented early) - BP in the upper limb is higher than BP in the
- Systemic hypertension(older children & adults) lower limb
b) Severe - ± Systolic murmur over the upper left sternal
- Duct-dependent circulation & circulatory edge or back
collapse in neonate

Investigations:
CXR ECG Echocardiography
- Rib notching (development of - Signs of LVH (Dominant R at - Evaluates heart structure &
large collateral intercoastal V5,V6; Deep S in V1,V2, total >7 function, assess blood flow
arteries running posteriorly to big squares) pattern, coarctation size
bypass obstruction

V1

V6

139
Management:
Neonatal severe CoA:
- Frequently associated with large malaligned VSD, intractable heart failure
- Sick infants require temporary stabilisation:
- Mechanical ventilation
- Correction of metabolic acidosis, hypoglycaemia, electrolyte disorders
- IV Prostaglandin E (Prostin) infusion
- Early surgical repair (single-stage CoA repair) + VSD closure or 2-stage CoA followed by VSD
closure at later date)

Asymptomatic/older children with discrete CoA:


- Presents with incidental hypertension or heart murmur
- Choice of treatment (primary transcatheter balloon angioplasty, stent implantation/ surgical
repair) depends on morphology of CoA & age of presentation)

Coarctation Repair (Surgical Approach):




















140
Cyanotic Congenital Heart Disease

1) Tetralogy of Fallot

Introduction:
- Most common
congenital heart disease
- Most are diagnosed
antenatally
- 4 cardinal features:
- Ventricular septal defect
- Pulmonary stenosis
- Right ventricular
hypertrophy
- Overriding aorta

Clinical features:
Symptoms Signs
- Most present with a murmur in the first 2 - Cyanosis, Clubbing (earliest clubbing: 6 months)
months of life - Loud & harsh ejection systolic murmur (ESM) at
- Cyanosis develops later (after a few months) left sternal edge (pulmonary area) from D1 of life
- Life threatening hypercyanotic spells (rapid - Single second heart sound (A2)
increase in cyanosis, usually associated with
irritability or inconsolable crying due to severe * With increasing right ventricular outflow tract
hypoxia, breathlessness & pallor) obstruction, the murmur duration will shorten
- May lead to MI, CVA, & death if untreated while the cyanosis will be worsened (infundibular
- Squatting following exertion in older child spasm).

Investigations:
CXR ECG Echo & Cardiac Catheterisation
- Boot-shaped heart (uplifting - Right axis deviation - Show detailed anatomy of
apex due to RVH), oligaemic - Right ventricular hypertrophy pulmonary arteries
lung fields, PA bay - Tall P wave (P pulmonale for
right atrial enlargement)

141
Management:
Conservative Surgical
- Hypercyanotic spells - Temporary surgery
- Usually self-limiting & followed by a period of - To increase pulmonary blood flow
sleep - eg. Modified Blalock-Taussig shunt for very
- Prompt treatment if prolonged >15 minutes cyanosed infants
- Morphine ( sedative )
- Oxygen, knees to chest position - Corrective surgery
- Propanolol (relieve infundibular spasm + - Usually done at 6 months of age
peripheral vasoconstriction)
- Bicarbonate (corrects acidosis)
- Muscle paralysis and artificial ventilation
(decrease metabolic oxygen demand)
- More potent vasoconstrictors (eg. phenylephrine
and noradrenaline)

Modified Blalock-Taussig shunt


- Creates L > R shunt via anastomosis of subclavian
artery to pulmonary artery
- Increased pulmonry flow distal to RV outflow
obstruction
- Cyanosis is reduced by increased proportion of
oxygenated blood
- Indications:
- Hypercyanotic spells/severe cyanosis <6 month
(too young for total repair)
- Small pulmonary arteries (to promote growth
before definitive repair)
- Anomalous coronary artery crossing in front of RV
outflow tract (preludes transannular incision, repair
with conduit (later age)

Hypercyanotic spells
- Sudden severe episodes of intense cyanosis caused
Complications: by reduction of pulmonary flow
- This is due to spasm of the right ventricular outflow
- Infarction tract or reduction in systemic vascular resistance
- Polycythaemia (hyperviscosity syndrome) (eg. hypovolaemia) with resulting increased in right
- Cerebral abscess (R>L shunt, paradoxical embolism) to left shunt across the VSD, releasing lactate, leads
- SBE/IE to metabolic acidosis
- Clinical feature:
- Failure to thrive
- Peak incidence: 3-6 months
- Often in morning, precipitated by crying, feeding,
If TOF patient without murmur, consider: defaecation
- Severe cyanosis, hyperpnoea, metabolic acidosis
- Concurrent pulmonary atresia (silent heart)
- Severe: syncope, stroke or death
- Develops polycythaemia - Reduced intensity of systolic murmur during spell
- Management:
- Treat as medical emergency, knee-chest/squatting
position (place baby on mother`s shoulder with
knees tucked up underneath (calming effect,
reduce systemic venous return, increase TPR)
- Give 100% O2, IV/IM/SC morphine 0.1-0.2mg/kg to
reduce distress & hyperpnoea.
- If fails, give IV propanolol slow bolus/IV Esmolol
with volume expander. IV sodium carbonate.
- In resistant case, consider IV Pneylephrine/
noradrenaline increase TPR, reduce R>L shunt.

142
2) Transposition of Great Artery (TGA)

Introduction:
- Aorta is connected to RV, pulmonary
artery is connected to LV (discordant
ventriculo-arterial connection)
- Deoxygenated blood is therefore
returned to the body while
oxygenated blood returns to lungs
- Two parallel circulations are
incompatible to life unless there is
mixing of blood between them (eg.
VSD, ASD, PDA)

Clinical features:
Symptoms Signs
- Cyanosis, may be profound & life threatening, - Cyanosis +/- finger clubbing (rare)
usually in the first few days (eg. day 2) of life, - ± Systolic murmur (due to increased flow within
leads to marked reduction in mixing of oxyge- LV (pulmonary outflow tract)
nated and deoxygenated blood - Acidosis
- Cyanosis will be less severe and delayed if there - Single second heart sound
is more mixing of blood from associated
anomalies eg. VSD, ASD, PDA

Investigations:
CXR ECG Echo & Cardiac Catheterisation
- Egg-on-side appearance, - Rarely helpful - Show detailed anatomy of heart
often increased pulmonary with transposition of aorta and
vascular markings pulmonary artery

Egg-on-side appearance:
- Due to anteroposterior
relationship of great vessels
- Narrow vascular pedicle &
hypertrophied RV.

Management:
Simple TGA (intact - IV Prostaglandin E infusion promotes intercirculatory mixing at PDA
ventricular septum) - Temporary surgery: Early Balloon Atrial Septostomy (BAS) if restrictive
interatrial communication
- Definitive surgery: Arterial switch operation at 2-4 weeks age
- LV regression may occur if repair not performed within 4 weeks of life

143
TGA with VSD - Does not usually require intervention during early neonatal period
- May develop heart failure at 1-2 months age
- Elective 1-stage arterial switch operation + VSD closure <3 months age
TGA with VSD & PS - Blalock-Taussig shunt during infancy followed by Rastelli repair at 4-6
years of age

Balloon Atrial Septostomy (BAS):

Arterial Switch:

3) Artrioventricular Septal Defects (Complete AVSD)

Introduction:
- Special form of VSD
- Ranges from ASD primum to
a large defect within a
common AV valve
- Most commonly seen in
children with Down syndrome
- Defect in middle of heart with a
single 5-leaflet valve between AV
junction & tends to leak
- Large defects lead to pulmonary
hypertension
Presentation:
- Present at antenatal ultrasound screening
- Detected through routine ultrasound screening for baby with Down`s syndrome
- Cyanosis at birth or heart failure at 2-3 weeks of life with no murmur
Treatment:
- Treat heart failure medically
- Surgical repair at 3-6 months
144
4) Tricuspid Atresia

Introduction:
- Only left ventricle is effective
- Right ventricle is small and non-
functioning (underdeveloped)
- There is common mixing of
systemic & pulmonary venous
return in LA

Clinical features:
- Cyanosis in the newborn which is duct-dependant
- Well at birth and become cyanosed and breathless
- ECG (left axis deviation) is diagnostic

Management:
Temporary surgery Corrective surgery
- Blalock Taussig shunt (for cyanosed infants) - Semi Fontan/ Glenn operation at 6 months of age
- Pulmonary artery banding (for breathless - Fontan operation at 3-5 years of age
infants)

Fontan procedure:
First stage: Bi-directional Glenn (graft reroutes from SVC to PA and to lung for oxygenation, bypass RA)
Second stage: Fontan (graft & internal baffle re-route rom IVC to PA)

145
5) Hypoplastic Left Heart Syndrome

Introduction:
- Underdevelopment of entire left side of the heart
- Left ventricle is diminutive
- Mitral and aortic valve are usually atretic
- Ascending aorta is usually very small
- ASD

Clinical features:
- Sickest of all neonates with duct-dependant
circulation
- Profound acidosis & rapid cardiovascular collapse
(due to absence of blood flow in the left heart
and ductal constriction )
- Weakness or absence of all peripheral pulses
- Failed hyperoxia (nitrogen washout) test

Management:
- Maintain ABC and immediate initiation of prostaglandin infusion
- Complex surgical correction (Norwood procedure)

Norwood procedure:

146
6) Total Anomalous Pulmonary Venous Connection (TAPVC)

Introduction:
- Connection of all pulmonary veins to
somewhere other than LA (1-3% of
congenital heart lesions)
- Pulmonary veins connect to:
- Supradiaphragm (70%)
- Vein (commonest innominate vein)
- Heart (coronary sinus or RA)
- Infradiaphragm (25%) - obstructive
- Portal vein or its branches
- Ductus venosus
- Mixed (5%)

Clinical features:
A) Obstructive
- Marked cyanosis (from decreased
pulmonary blood flow accentuated
by pulmonary oedema & pulmonary
arterial hypertension)
- Tachypnoea, Respiratory distress
B) Non-obstructive
- Minimal cyanosis
- CCF (pulmonary overcirculation)

Management:
- Surgical with anastomosis of
pulmonary vein confluence to LA
(extracardiac anomalous connection)
- Unroofing coronary sinus (sinus type)
- Repositioning of atrial septum (RA type)

Surgery for TAPVR to Left SVC: Surgery for TAPVR to Coronary Sinus:

147
7) Truncus Arteriosus
Introduction:
- Denotes a single
arterial trunk
serves ascommon
origin of aorta,
pulmonary artery
& coronary arteries
- 2-2.8% of
congenital heard
lesions
- Almost always
associated with
a VSD
- Associated heart
defect include
right aortic arch
(33%)

Clinical features:
- Minimal cyanosis (hihgh pulmonary blood flow)
- Tachypnoea, Respiratory distress
- CCF exaggerated by poor coronary perfusion 2` to low diastolic pressure from runoff into PA

Management:
- Surgical separation of aorta & pulmonary artery, placement of extracardiac RV to PA conduit,
closing VSD by baffling LV to aorta (refer diagram above)

8) Ebstein`s Anomaly of Tricuspid Valve


Introduction:
- Rare, displacement of attachment of septal & posterior leaflets of tricuspid valve toward apex
of right ventricle (RV)
- Risk factors: Children of mothers taking lithium
- Patients have high incidence (20-30%) of pre-exicitation with accessory pathway
Clinical features:
- Cyanosis
- Atrial arrythmias
- Right-sided heart failure (adolescence)
Management:
- Depends on degree of tricuspid regurgitation
& presenting symptoms
- Early surgical intervention has had poor result
- Tricuspid annuloplasty & valvuloplasty have
good results in recent years

148
Rheumatic Fever

Introduction:
- Inflammatory disease that involves heart, joints, CNS, skin & subcutaneous tissues

Epidemiology:
- Most common cause of acquired heart disease in children & adult
- Mainly in under developed countries
- First infection is usually between 5-15 years of age (F>M)
- Extremely rare in infancy and <4 years old children
- Associated with adverse social economic factors, medical care & overcrowding

Aetiology:
- Group A β-haemolytic Streptococcus untreated pharyngitis in susceptible individual
- It has been confirmed this genetic susceptibility is inherited as autosomal recessive (AR) gene

Pathogenesis:
- Streptococci trigger autoimmune reaction à inflammation
- NOT direct infection from the bacteria to the heart
- Antibody produced by the infection showed to cross react with host tissue in the valvular
tissue, myocardium, joint, subthalamic & caudate nuclei
- The inflammatory lesion is in many systems à valvular damage in mitral & aortic, less in
tricuspid & pulmonary
- Characteristic Aschoff bodies in atrial myocardium (inflammatory lesion + swelling +
fragmented collagen fibres)

Clinical features:
- History of pharyngeal infection or URTI for previous 2-6 weeks

Revised Jones Criteria


Major Criteria Minor Criteria
Joint - Migratory polyarthritis (80%) - Fever
O - Pancarditis (50%) - Polyarthralgia (not if arthritis is one of the major
N - Subcutaneous nodule (rare) criteria)
E - Erythema marginatum (< 5%) - Previous history of rheumatic fever or rheumatic
S - Sydenham`s chorea (10%) heart disease
- Raised acute phase reactants (ESR>30mm/hr,
CRP>30mg/L and leucocytosis)
- Prolonged PR interval (same as arthralgia)

Definite Diagnosis:
- 2 major criteria OR 1 major + 2 minor infection
- With supporting evidence of preceding streptococcal infection
- History of scarlet fever
- Positive throat swab (for group A streptococcus)
- Raised anti-streptolysin O titre (ASOT) >200U/ml or anti-DNAse B

149
Clinical features Description
Sydenham`s - Usually occurs 2-6 weeks after Streptococal infection
chorea - Characterised by: (3-6 months)
(St Vitus dance) - Involuntary, purposeless movements
- Followed by motor weakness & hypotonia
- Preceded by emotional lability
- Physical signs:
- Pronator sign à extension of the arms above the head produces
pronation of the 1 or both hand
- Milking sign à ask the patients to squeeze the examiner finger,
irregular contraction of the muscle of the hand will be evident
- Spoon/Dishing sign à extension of the hand forward will lead to
hyperextension of the finger

Subcutaneous - Usually found on the extensor surface of joint & occasionally on the scalp
nodule or spine
- Clinical features:
- Painless & free mobile
- Pea-sized & hard

Migratory - Usually involve larger joints (eg wrists, knees & ankles)

polyarthritis
Symptoms Signs
- Arthralgia which is fleeting - Joints involved
- Lasting <1 week - Redness
- Asymmetrically & migrating to other - Swelling
- Joints over 1-2 months - Tender
- Limitation of movement & non- - Very responsive to salicylates
damaging

Pancarditis - Variable severity


- Clinical features:
- Tachycardia during sleep
- Pathological murmur of valvulitis : MR +/- AR
- Progressive cardiomegaly in CXR, signs of CCF & atrial fibrillation (AF)
- Consists of 3 major components:
- Endocarditis
- Myocarditis
- Pericarditis
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Endocarditis Myocarditis Pericarditis
- Significant murmur - May lead to heart - Pericardial friction rub
- Valvular dysfunction failure & death - Pericardial effusion
- Cardiac tamponade

Erythema - Uncommon early manifestation


marginatum - Characteristic skin rash
- Appears on trunk & limbs
- Non-pruritic, pink macules spread
outwards à pink borders with fading
centre
- Borders may unite to give a map-like
outline

Complications:
- Causes scarring & fibrosis of valve tissue
- Mitral valve ( 85% ) à Mitral stenosis
- Aortic valve ( 55% )
- Tricuspid valve & pulmonary valves ( <5% )

Clinical course & Prognosis:


- Abrupt onset in patient with fever and arthritis
- Insidious onset in patients with chorea
- Patients may also present with fever and carditis in failure
- Worst prognosis if patients have
- Carditis
- Repeated attacks
- Residual valvular heart disease increases chances of recurrence

Management:
Acute Phase Secondary Prophylaxis
- Evaluate FBC, ESR, CRP, CXR, ECG, Echo, & ASOT - Duration of prophylaxis is controversial
- Encourage bed rest & limitation of exercise - Lifelong for patients with carditis & valvular
- Eradication of Grp A β-haemolytic Streptococci involvement
- Penicillin V 250mg 6 hourly x 10 days (children), - Until age 21 years or 5 years after last attack of
500mg 6 hourly (adolescents) ARF whichever was longer
- For patients with allergy to penicillin, - Penicillin
erythromycin or cephalosporin is used - Monthly IM benzathine Penicillin(most effective)
- Anti-inflammatory agents (suppress - Oral penicillin V BD is an alternative
inflammatory response in joints or heart) - Oral erythromycin (if allergic to penicillin)
- High dose aspirin
- Corticosteroids (if fever & inflammation do not
resolve rapidly)
- Treat associated problems
Cardiac failure Diuretics & ACE inhibitor
Pericardial effusion Pericardiocentesis

151
Mitral Stenosis

Introduction:
- In children it is mostly congenital, commonest RHD in adults

Pathology:
- Fibrosis of the leaflets, fusion of rings with calcification & immobility
- Left atrium, right side heart enlarged and hypertrophied
- Followed by pulmonary venous hypertension, pulmonary oedema & right heart failure

Clinical features:
- Asymptomatic or symptomatic on exertion, rarely related to AF & IE.
- Dyspnoea, orthopnea, paroxysmal nocturnal dyspnea
- Palpitation, hemoptysis

Physical findings:
- Left parasternal heave (RV hypertrophy), weak peripheral pulse, Normal Pulse Pressure
- Right heart failure: Distended neck veins, raised JVP, hepatomegaly, ascites & oedema
- Functional Tricuspid regurgitation, pansystolic murmur
- Loud S1 (tapping apex beat)
- Narrow split of S2, maybe loud
- Opening snap soon after S2
- Mid-diastolic rumbling at apex with presystolic accentuation
- Graham Steell (pulmonary regurgitation at upper left sternal border, early diastolic, inspiration,
due to pulmonary hypertension)
- Ejection click

Investigations:
ECG - RA dilatation, LA hypertrophy, RV hypertrophy due to pulmonary hypertension
- AF rare in children
CXR - LA, RV enlargement, pulmonary venous congestion with interstitial oedema
(Kerley B lines), calcifications
Echocardiography - Most accurate

Management:
Medical Surgical
- Good oral hygiene & prophylaxis vs acute - Indicated in
rheumatic fever & IE - Symptomatic patient
- Varying degree of activity restriction - Recurrent AF
- Digoxin for AF, anticoagulation to all MS - Thromboembolism
patients - Hemoptysis
- Balloon valvuloplasty, M-commissurotomy or
replacement if calcification presents

152
Mitral Regurgitation

Introduction:
- The most common Rheumatic involvement in children

Pathology:
- Loss of valve tissue, shortening & fibrosis of leaftlets
- Left ventricle enlarges, left atrium dilates with increased pressure à followed by pulmonary
edema & CHF

Clincial features:
- Asymptomatic mild & moderate disease, rarely get fatigue & palpitation with atrial fibrillation
- Stable for long duration, but MS may supervene
- Can develop LVF & pulmonary hypertension in adult life

Physical findings:
- JVP is normal in the absence of CHF
- Heaving cardiac impulse if severe
- S1 is normal or decreased
- S2 widely split, may be loud
- S3 present & loud
- Pansystolic murmur, grade 2-4/6, at the apex with radiation to the axilla, best on left lateral
decubitus position
- Short diastolic rumble maybe present at apex due to increased flow through the valve

Investigation:
ECG - LV dominance, LVH, AF develops in adults
CXR - LV/LA enlargement, CHF with PVC
Echo - Severity related to degree of dilatation of LV/LA
Catheterization - Left ventriculography

Management:
- Prophylaxis against acute rheumatic fever recurrence & IE
- CHF: Digoxin (also for AF), diuretics
- Indications for surgery :
- Intractable CHF
- Progressive cardiomegaly with symptoms
- Pulmonary hypertension
- It is either valvuloplasty or valve replacement if thick and scarred









153
Aortic Regurgitation

Introduction:
- Usually combined with Mitral Regurgitation
- Remains asymptomatic for long duration but symptomatic if started they deteriorate rapidly
- Rare in IE patients

Pathology:
- Semilunar cusps deformed, ring dilated so they fail to oppose tightly

Clinical features:
- If severe AR or in CHF they will have exercise intolerance
- Angina, CHF & multiple pulmonary venous congestions are unfavourable signs

Investigation:
ECG LV hypertrophy in severe AR, chronic LA hypertrophy
CXR Cardiomegaly of LV, prominent aortic knuckle, pulmonary venous
congestion if in LV failure
Echo Detects severity of AR

Management:
Medical Surgical
- ARF & IE prophylaxis - Indication for surgery
- CHF (Digoxin & diuretics) - Angina or dyspnoea on exertion
- Cardiomegaly even if asymptomatic à valve
replacement or pulmonary root autograft






















154
Infective Endocarditis (IE)

Definition:
- Microbacteria infection à Exudative & proliferative inflammatory alterations of the
endocardium or vascular endothelium

Introduction:
- IE is a rare but very serious complication of patient with structural heart disease
- Typically affect older children with structural heart disease
- 2 factors in its pathogenesis:
- Structural abnormality of heart or great artery by turbulent flow à platelet-fibrin deposition
à Non-bacterial thrombotic endocarditis à Adherence
- Bacteremia resulting in endothelial damage & platelet à Adherence à Colonisation à Fibrin
thrombus (vegetation) formation

Aetiology:
Bacteria Fungus Others
- Streptococcus viridans - Candida albicans - SLE
(Bacterial flora of pharynx & - Aspergillus (Libman-Sacks endocarditis)
upper respiratory tract, - Histoplasma
dental procedures) - Cryptococcus neoformans
- Staphylococcus aureus
- Enterococcus fecalis
- Staphylococcus epidermidis
- Gram -ve organisms (rare)
- HACEK group
- Haemophilus spp
- Actinobacillus
actinomycetemcomitans
- Cardiobacterium hominis
- Eikenella corrodens
- Kingella kingae
- Coxiella burnetii (Q fever)
- Chlamydia

Risk groups:
- IV drug abuser
- Patients with congenital heart disease or rheumatic heart disease
- After cardiac surgery (prosthetic valves)
- Chronic IV catheterization
- Immunosuppressants

Clinical features:
- Fever + new murmur is endocarditis until proven otherwise
(Common symptoms: Unexplained, remitting fever >1 week, LOW, LOA, myalgia)

155
Symptoms Signs
- Fever Hands & limbs
- Malaise - Peripheral stigmata of infective endocarditis
- Anorexia - Clubbing (late)
- Weight loss - Splinter haemorrhage
- Arthralgia - Osler nodes
- History of predisposing factors, procedures (eg - Janeway lesion
dental, surgical), central venous catheter - Necrotic skin lesion
insertion - Pallor (due to anemia)

Head
- Roth`s spot on fundoscopy (retinal infarcts)

CNS
- Neurological signs from cerebral infarction

CVS
- New/ changing cardiac murmur

GIT
- Splenomegaly

Genitourinary
- Microscopic hematuria

Musculoskeletal
- Arthritis (arthralgia)

Definite Diagnosis: (Based on Modified Duke Criteria)


- 2 major criteria OR
- 1 major + 3 minor criteria OR
- All 5 minor criteria (no major criterion met)
Major criteria Minor criteria
- Positive blood culture - Predisposing factors:
- Typical organism in 2 separate cultures - Congenital heart disease **
OR - Rheumatic heart disease
- Persistently +ve blood cultures - Prosthetic valve or other intracardiac
- ≥2 blood culture drawn >12 hours apart prosthesis
- A +ve blood culture for Coxiella burnetii - IVDU
or +ve IgG titer >1: 800
- Fever >38`C
- Positive echocardiogram
- Vegetation*, abscess or dehiscence of - Vascular /Immunological signs ***
prosthetic valve - Positive blood culture that does not meet
OR major criterion
- New valvular regurgitation
(change in murmur is not sufficient) - Positive echocardiogram that does not meet
major criterion
* Vegetations consist of:
- Fibrin, platelets, infecting organisms

156
**Congenital heart disease
- Highest risk if there is a turbulent jet of blood:
- VSD
- Coarctation of Aorta (COA)
- Patent ductus arteriosus (PDA)
- Exception for AS
*** Vascular phenomena (major arterial emboli, septic pulmonary infarcts, mycotic aneurysm,
intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions),
Immunological phenomena (GN, Osler nodes, Roth spots, rheumatoid factor)

Possible IE - 1 major + 1 minor criteria OR


- 3 minor
Rejected IE - Firm alternative diagnosis
- Resolution of symptoms with antibiotics therapy <4 days
- No pathological evidence of IE at surgery/autopsy
- Not meet criteria for possible IE

Investigations:
Blood - FBC
- Normochromic normocytic anemia (unexplained)
- Polymorphonuclear leucocytosis (evidence of bacterial infection)
- Thrombocytopenia (occasionally)
- Acute phase reactant
- Increased ESR & CRP (indicate inflammation)
- Blood C&S
- For evidence of bacteremia of typical organism
- Serum immunoglobulin & complement (Raised)
- Low total complement & C3 complement
- LFT (mildly disturbed)
- Raised alkaline phosphatase (ALP)
- Serology (chlamydia, candida, coxiella, brucella) if culture negative
Urine - UFEME
- Microscopic hematuria
- Urine dipstick (proteinuria)
Imaging - Echocardiogram (visualise endocardial & valvular vegetations measuring
≥2mm. Transesophageal more sensitive than transthoracic in adolescent
or adult with prosthetic valve but often unnecessary for children

Prognosis:
- Prognosis is variable
- Mortality is high ( 20-30% of patients particularly )
- Acute staphylococcal infection
- Fungal infection
- Infected prosthetic material
- Survivors at risk of recurrence

Management:
- Can be divided into conservative and surgery
- Ensure 3 blood cultures taken before antibiotic therapy, do not wait for echocardiography
- Use empirical antibiotics, until culture results available
157
Conservative Surgery
- Intravenous antibiotic (bactericidal agents) - Adjunct to medical therapy in certain
for 4-8 weeks à for bacterial endocarditis circumstances
- Monitor clinical response (+ acute phase - Less chance of complete eradication
reactant) - Indications:
- Commonly used is high-dose penicillin in - Infected prosthetic materials
combination with aminoglycosides - Prosthetic valves
- VSD patches or shunts
- Embolization & large vegetations
- Progressive cardiac failure
- Worsening renal failure

Antibiotic choices for Infecitve Endocarditis in Children:


Organisms Antibiotic of choice Duration of
involved treatment
Streptococcal IV Penicillin (or IV Vancomycin if sensitive to Penicillin) 4 weeks
eg. Strep viridans AND
IV Gentamicin OR IV/ IM Ceftriaxone
Enterococci IV Ampicillin (or IV Vancomycin if sensitive to penicillin) 4 weeks
eg. Enterococcus AND
faecalis IV Gentamicin
Staphylococci IV Cloxacillin (or Penicillin if Penicillin sensitive or 4 weeks
eg. Staph aureus Vancomycin if MRSA)
or epidermidis AND
IV gentamicin (or fusidic acid)
Gram negative IV ampicillin 4 weeks
endocarditis OR
IV cephalosporin (eg ceftriaxone) if resistant to ampicillin

Culture negative IV cloxacillin (vancomycin if penicillin allergic) 6 weeks


endocarditis AND
IV gentamicin
Fungal Amphotericin B 6-8 weeks
endocarditis
- Stop gentamicin after 2 weeks, monitor gentamicin level and renal function
- Substitute streptomycin for gentamicin if resistant to gentamicin and treat for at least 6 weeks
- Stop gentamicin (or fusidic acid) after 1 week
- Surgical removal of infective tissue after 1-2 weeks medical treatment

Prophylaxis
1) Procedures requiring prophylaxis
Oral, dental Dental surgery(eg. tooth extraction, placement of orthodontic bands)
Respiratory system Tonsillectomy, adenoidectomy
Rigid bronchoscopy, Flexible bronchoscopy with biopsy
GIT Sclerotherapy (oesophageal varices), Oesophageal stricture dilatation
ERCP, Appendicectomy
Genitourinary Cystoscopy, Urethral dilatation

158
2) Prophylactic Regimen
Oral, Dental - Ampicillin before procedure
Respiratory Tract - Clindamycin if allergic to Ampicillin
Esophagus

GIT - Ampicillin + Gentamicin OR


Genitourinary - Vamcomycin + Gentamicin (if allergic to Penicillin)

3) IE prophylaxis recommended for


High-risk category - Prosthetic heart valves
- Previous bacterial endocarditis
- Complex cyanotic congenital heart disease
- Surgical systemic pulmonary shunts or conduits
Moderate-risk - Other congenital heart defects (other than high/low risk category)
category - Acquired valvular dysfunction (eg. RHD)
- Hypertrophic cardiomyopathy
- Mitral valve prolapse with regurgitation
NOT recommended - Isolated secundum ASD
in negligible-risk - Repaired ASD, VSD, PDA (>6 months)
category - Mitral valve prolapse without regurgitation
- Functional or innocent heart murmurs
- Previous Kawasaki disease without valvular dysfunction
- Previous Rheumatic fever without valvular dysfunction
- Cardiac pacemakers & implanted defibrillators

Complications of embolic effects of infective endocarditis:

159
Kawasaki Disease (Mucocutaneous Lymph Node Syndrome)
Introduction:
- Systemic febrile condition, infantile polyarteritis of unknown case
- It is one of the most common vasculitides of childhood (70-80% together with HSP)
- First describe in Japan in 1967
- Results from immune hyperactivity to a variety of triggers in a genetically susceptible people
Epidemiology:
- 80% of patients are <5 years old (6 months-4 years old)
- Peak incidence at the end of first year
- More severe in young infants compared with older child
- All races affected but highest incidence in Asian
population
- Commoner in boys (M : F = 1.5 : 1)
Red, cracked lip & conjunctival inflammation.
Aetiology: Peeling of fingers, developed on 15th of illness
- Unknown
- Probable association with microbial agents (staphylococcal & streptococcal)
- Bacterial toxin acts as superantigen
Pathology:
- Vasculitis of small and medium-sized vessels (eg. coronary arteries)
- Inflammatory process involves the entire vascular wall à aneurysm +/- thrombus
- Eventually results in intimal proliferation, scarring, calcification, stenosis & recanalization
Clinical features: (diagnostic criteria)
- Acute fever for at least 5 days + 4/5 of the following features:
- Other diagnosis need to be excluded (diagnosis of exclusion)
Eye - Bilateral conjunctival injection without exudate
Mucosal changes in mouth - Injected pharynx
- Strawberry tongue
- Cracked and erythematous lips
Neck - Cervical lymphadenopathy (>2 LN & >1.5 cm)
Body - Polymorphous exanthema, maculopapular rash or perianal rash
/generalised rash
Changes in extremities - Redness & swelling of the hands and feet
- Desquamation, peeling of the finger (convalescent phase)

- Other features/ Complications:


CNS - Aseptic meningitis
- Extreme irritability
- Altered mental state
CVS - Coronary abnormalities (eg. coronary artery aneurysm)
- Pericarditis, myocarditis
- Myocardial infarction, heart failure
GIT - Diarrhea, vomiting, abdominal pain
- Hepatosplenomegaly
- Gallbladder hydrops
Musculoskeletal - Arthritis (+ arthralgia) in small or large joint
Others - Erythema & induration at BCG site, Sterile pyuria

160
Disease Progression:

Most important complication is coronary vasculitis, usually within 2 weeks of illness, affecting up
to 25% of untreated children. Usually asymptomatic, it may manifest as myocardial ischaemia,
infarction, pericarditis, myocarditis, endocarditis, heart failure or arrhythmia.

Investigations:
Blood - FBC
- Anemia (low Hb)
- Neutrophilia (low WBC)
- Thrombocytosis (high PLT - in convalescent phase)
- Acute phase reactant
- Increased ESR & CRP (indicate active inflammation)
- ANA & RA factor (negative)
- LFT (Elevated serum transaminases and hypoalbuminaemia <3g/dl)
Urine - UFEME (Pyuria >10 wbc/hpf)
Imaging - Echocardiography (In the acute phase and repeat at 6-8 weeks or earlier
if indicated)
Others - ECG
- Prolonged PR interval
- Deep Q wave
- ST & T wave changes
- CXR
- Normal or reticulonodular pattern (89.5%)
- Peribronchial cuffing (21.1%
- Pleural effusion (15.8%)
- Atelectasis (10.5%)

161
Management:
Medical General Measures
- IV immunoglobulin (within first 10 days of illness) - Serial echocardiogram
- Lower risk of coronary artery aneurysm - Long-term cardiology follow-up for those with
- Fever and systemic complaints resolve within coronary artery abnormalities
24-48 hours

- Salicylate within for 2 weeks or until patient is


afebrile for 2-3 days

- Aspirin (reduces risk of thrombosis)


- High dose in acute stage (anti-inflammatory
action) until fever subsides
- Low dose after acute stage (anti-platelet action)

Prognosis:
- Mortality 1-2% usually from cardiac complications within 1-2 months of onset
- Recovery is complete in children who do not have coronary artery involvement, 80% of
aneurysm 3-5mm in diameter resolve, 30% of 5-8mm aneurysms resolve
- Prognosis worst for aneurysms >8mm in diameter
Incomplete Kawasaki Disease
- Patients who do not fulfill the classic diagnostic criteria (outlined in previous page)
- Tends to occur in infants and the youngest patients
- High index of suspicion should be maintained for diagnosis of incomplete KD
- Higher risk of coronary artery dilatation or aneurysm occurring
- Echocardiography is indicated in patients who have prolonged fever with:
- Two other criteria
- Subsequent unexplained periungual desquamation
- Two criteria + thrombocytosis
- Rash without any other explanation
Atypical Kawasaki Disease
- For patients who have atypical presentation, eg. renal impairment, that generally is not seen in
Kawasaki Disease
- Treatment:
Primary treatment
- IV Immunoglobulins 2 Gm/kg infusion over 10 - 12 hours. Therapy < 10 days of onset effective in
preventing coronary vascular damage.
- Oral Aspirin 30 mg/kg/day for 2 wks or until patient is afebrile for 2-3 days.
Maintainence:
- Oral Aspirin 3-5 mg/kg daily (anti-platelet dose) for 6 - 8 weeks or until ESR & platelet count
normalise
- If coronary aneurysm present, then continue aspirin until resolves
- Alternative: Oral Dipyridamole 3 - 5 mg/kg daily.
Kawasaki Disease not responding to Primary Treatment
- Defined as persistent/ recrudescent fever ≥ 36hrs after completion of initial dose of IVIg
Treatment
- Repeat IV Immunoglobulins 2 Gm/kg infusion over 10-12 hours
- Vaccinations
- Use of Immunoglobulins may impair efficacy of live-attenuated virus vaccines
- Delay these vaccinations for at least 11 months

162
PART V

RESPIRATORY
Common Respiratory Infections

Introduction:
- Most common cause of death in children worldwide.
- Preschool child has, on average, 6-8 respiratory infections a year.
- Cystic fibrosis is the most common inherited life-limiting disorder in Caucasians.
- Children are prone to respiratory infection especially <2 years old due to smaller airways (easily
blocked), lower resistance and immunity.
- Pathogens (viral-caused: 80-90% of childhood respiratory infections):
RSV Parainfluenza Influenza AdenoV EnteroV RhinoV Mycoplasma
Colds + + + ++ ++ ++++ +
Tonsillitis/ ++ ++ +
Pharyngitis
Otitis media + + + +
Laryngotracheitis + ++++ + +
Bronchitis + + + +
Bronchiolitis ++++ ++ + + +
Pneumonia ++ + + ++
* Viruses & Mycoplasma commonly associated with acute respiratory infection, diagnosis is from nasopharyngeal
aspirate

- Pathogens (bacterial-caused: commonly associated with acute respiratory infection):


Streptococci Haemophilus Streptococcus Staphylococcus
influenza pneumoniae aureus
Tonsillitis ++
Pharyngitis ++
Otitis media + + +
Epiglottitis +++
Laryngotracheitis
Bronchitis
Bronchiolitis
Pneumonia + +++ +

- An increased risk of symptomatic respiratory infection is associated with:


- Poor socioeconomic status (over-crowding, damp housing, large family size)
- Poor nutrition
- Parental smoking, especially maternal
- Gender (Boy > Girl)
- Prematurity especially those who required artificial ventilation/ prolonged oxygen therapy
- Cystic fibrosis, Asthma
- Congenital abnormalities of the lungs and heart
- Immunodeficiency
- Primary/ congenital (hypogammaglobulinaemia)
- Secondary/ acquired (from HIV infection/ chemotherapy)
- Classification (according to level of respiratory tract):
- Upper respiratory tract infection (URTI)
- Laryngeal/ tracheal infection
- Bronchitis
- Bronchiolitis
- Pneumonia
163
Clinical features of respiratory distress:
Symptoms Signs
- Breathlessness - Tachypnoea
- Difficulty feeding or talking - Tachycardia
- Wheeziness - Dyspnoea
- Sweatiness - Recession (intercostal, subcostal & suprasternal)
- Nasal flaring
- Use of accessory muscles of respiration
(shoulders up, lean forward, head bobbing-infants)
- Expiratory grunting
- Wheeze
- Crackles
- Cyanosis
- Liver ptosis (hyperinflation of lungs)
- Harrison`s sulcus
Differentiate viral and bacterial infections (as general):
Viral Bacterial
- High-grade fever - Mild to moderate fever
- More severe cough, breathlessness - Can be severe cough and breathlessness
- Wheezing - Occasional/no wheezing
- Sputum is white to colourless (not definitive) - Sputum is yellowish to greenish (not definitive)
- Normal neutrophils & CRP level - Raised neutrophils & CRP level
(unless 2` bacterial infection) - Normal lymphocytes level
- Elevated lymphocytes level - More toxic-looking and lethargy
- Less toxic appearance except dehydrated
Physical signs of pulmonary diseases:

Wheezing
- High-pitched musical sound produced by air flowing through narrowed airways.
- Heard mostly during the expiratory phase (normal tendency of the intrathoracic airways to narrow when
intrapleural pressure exceeds intraluminal pressure during expiration)
- Sign of increased airway resistance resulting from obstruction in intrathoracic airways.
- Heterophonous or polyphonic when there is diffuse narrowing of the airways. Most common causes of this
wheezing are viral bronchiolitis & asthma.
- Homophonous is when single set of pitches originates in larger airways but can be transmitted widely. Common
causes include tracheomalacia, bronchomalacia, foreign body aspiration & anatomic compression of airways.
Stridor
- Distinct harsh inspiratory noise due to obstruction occurs in the extrathoracic airways.

164
Upper Respiratory Tract Infection (URTI)

Introduction:
- Infection involving the nose, throat, ears & sinuses
- Approximately 80% of all respiratory infection

- Common URTI:
- Common cold (Coryza)
- Sore throat (Pharyngitis including tonsillitis)
- Acute otitis media
- Sinusitis (Relatively uncommon)

- Commonest presentation:
- Nasal discharge and blockage
- Fever
- Sore throat
- Ear pain

- URTI may lead to:


- Poor feeding due to nose block
- Febrile convulsion
- Acute exacerbation of asthma

1) Common Cold (Coryza)


- Commonest infection of childhood
- Commonest pathogen: Rhinoviruses, Coronaviruses, RSV (viral origin)
- Classical presentation:
- Initially clear and later mucopurulent nasal discharge -> Nasal blockage -> Fever and other
constitutional upset
- Usually self-limiting and have no specific curative treatment
- Fever and pain are best treated with Paracetamol/ Ibuprofen
- Antibiotics are of no benefit (viral origin)

2) Pharyngitis and Tonsillitis


- Commonest pathogens: Adenoviruses, Enteroviruses, Rhinoviruses (viral origin)
Goup A β-haemolytic streptococcus (in older children)
Epstein-Barr Virus (Infectious mononucleosis)
- Presentation: Sore throat, fever and malaise
- Examination: - Pharyngitis (Pharynx and soft palate are inflamed)
- Tonsillitis (Inflamed, reddened tonsil, often with purulent exudate)
- Clinically, it is not possible to distinguish bacteria/ viral origin of pharyngitis & tonsillitis.
However, marked constitutional disturbances (headache, apathy, abdominal pain, tonsillar
exudate, cervical lymphadenopathy) is more suggestive of bacterial infection.
- Symptomatic treatment with Paracetamol for fever and pain and encourage fluid intake.
- Antibiotic (often penicillin/ Erythromycin-if penicillin allergy) is often given for severe
pharyngitis and tonsillitis even though only 1/3 are caused by bacteria. Amoxicillin is best
avoided (can cause generalized maculopapular rash if it is due to Infectious Mononucleosis).

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3) Acute Otitis Media
- Acute infection of the middle ear
- Most children have at least 1 episode of acute otitis media (AOM)
- Most common at 6-12 months of age, up to 20% will have ≥3 episodes (Recurrent OM)
- Infant & young children prone to acute OM as their Eustachian tubes are short, horizontal &
function poorly.
- Common pathogens: RSV, Rhinoviruses, Adenoviruses (viral origin)
Streptococcus pneumoniae
Haemophilus influenza
Moraxella catarrhalis
- Presentation: Pain, irritable ear, fever
- Examination: Findings on tympanic
- Otoscopy/ tympanometry (tympanic membrane) - diagnostic membrane:
- Complication: - Bright red
- Mastoiditis - Bulging
- Meningitis - Loss of light reflection
- Pus visible in external canal
- Recurrent ear infection may lead to chronic serous otitis
(in acute perforation)
media (result in conductive hearing
loss)
- Management:
- 80% resolve spontaneously by 24 hours
- Symptomatic treatment for pain and fever (Paracetamol)
- Antibiotics: Amoxicillin/ Augmentin (Co-amoxiclav) - shorten duration of pain but not shown
to reduce hearing loss
- Neither decongestants nor antihistamines help in Eustachian Tube drainage

Chronic Serous Otitis Media (CSOM)/ Otitis media with effusion (OME/ Glue ear)
Introduction:
- Usually asymptomatic/ mild earache and resolves spontaneously
- Very common between ages of 2 & 7 years old, peak incidence 2.5-5 years old
- Most common cause of conductive hearing loss in children
- May interfere with normal speech development & result in learning difficulties in school
Investigations:
- Tympanometry (flat trace is diagnostic)
- Dull and retracted tympanic membrane
- Fluid level and air bubbles
- Pure tone audiometry (conductive loss, possible if >4 years old)
- Distraction test (reduced hearing, younger children)
Management:
- Grommets (Ventilation tubes) insertion
- Adenoidectomy +/- Tonsillectomy (which causes recurrent OM)
- Adenoids harbour organisms within biofilms contribute to infection spreading up to tubes
- Gross hypertrophied adenoids may obstruct & affect function of Eustachian tubes.
- Speech therapy

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Normal Acute otitis media Otitis media with effusion Grommet

4) Sinusitis
- Infection of paranasal sinuses
- Common pathogens : viral origin, occasionally with secondary bacterial infection
- Presentation: pain, swelling and tenderness over cheek (infection from maxillary sinus)
* Frontal sinusitis is uncommon since frontal sinuses do not develop until late childhood
- Management:
- Antibiotics and analgesics are used in addition to topical decongestants
- Concurrent use of intranasal corticosteriods/ antihistamines with antibiotics (hasten recovery)

Indication for Tonsillectomy and Adenoidectomy:


Only Tonsillectomy Both Tonsillectomy and Adenoidectomy
- Recurrent Tonsillitis - Otitis media with effusion with hearing loss
- Peritonsilar abscess (Quinsy) (esp if grommets reinsertion is considered)
- Obstructive Sleep Apnea (OSA) - Obstructive Sleep Apnea (OSA)
- absolute indication
* Adenoids (like tonsils) increase in size till age of 8 years & then gradually regress. In young children,
adenoids grow proportionately faster than airway, so narrowing effect on airway lumen is greatest
between 2 and 8 years of age. They may narrow posterior nasal space sufficiently to justify
adenoidectomy.

5) Choanal stenosis/atresia
- Congenital, presenting during neonatal period (cyanose when normal, pink when crying)
- Bilateral or unilateral and is relatively rare
- Neonates are generally obligate nose breathers, so obstruction of nasal passages can cause
significant respiratory distress, especially when feeding
- Crying bypasses the obstruction as crying infants breathe through their mouths
- Inability to easily pass a small catheter through the nostrils should raise the suspicion
- Diagnosis is confirmed by CT scan & inspecting area directly with a flexible nasopharyngoscope
- Oral airway may be useful in the short term, but definitive treatment is surgery

6) Apnoea
- Defined as the cessation of airflow due to
- Lack of respiratory effort (central apnea)
- Upper airway obstruction (obstructive apnea)
- Central apnea lasting <10 seconds is common in healthy infants & can be present in normal
children during sleep, especially after a sigh breath. Central pauses lasting >15-20 seconds are
considered abnormal. More common in infants
- Obstructive apnea, especially during sleep, is more common in older children.
167
- Premature infants can have apnea of prematurity, which consists of recurrent apneic episodes
that are often of central origin, though they can be mixed. It should resolve by 44 weeks
postconceptional age.

Categories of Apnoea:
Diseases Examples Mechanism Signs Treatment
Apnea of Premature Central control, upper Apnea, bradycardia Caffeine, HFNC,
prematurity (<36 weeks) airway obstruction CPAP, intubation
Central apnea/ CCHS, Arnold-Chiari Abnormal central Apnea Mechanical
hypoventilation malformation control ventilation
Obstructive sleep Obesity, Airway obstruction Snoring, restless Adenotonsillectom
apnea adenotonsillar due to excess tissue, sleep, enuresis, poor y, CPAP/BiPAP,
hypertrophy, Pierre loss of pharyngeal school performance, uvuloveloplasty,
Robin sequence, tone or crowded behavior problems, tracheostomy
Down syndrome, anatomy mouth breathing
cerebral palsy
Breath-holding <3 yr old who turns Prolonged expiratory Cyanosis, syncope, Reassurance;
spells blue after crying, apnea; reflex anoxic brief tonic-clonic condition is self-
may have syncope seizures movements after limiting. Must
cyanosis exclude seizure
disorder

Differential Diagnosis of Acute Upper Airway Obstruction:

168
169
Viral Croup (Laryngotracheobronchitis)

Definition:
- Progressive spread of viral inflammatory process down the respiratory tract involving larynx,
trachea & bronchi (till subglottic area around cricoid)
- Clinical syndrome characterised:
- Barking cough
- Inspiratory stridor
- Hoarseness of voice (due to inflammation of vocal cord)
- Respiratory distress of varying severity

Epidemiology:
- Occurs from 6 months to 6 years of age (peak incidence in 2nd year of life)
- Most severe in children <3 years of age
- Accounts for >95% of laryngotracheal infections

Aetiology: (mostly viral)


- Parainfluenza virus (74%, most common) types 1, 2 and 3
- Respiratory Syncytial Virus (RSV)
- Influenza virus types A & B
- Adenovirus, Enterovirus, Measles, Mumps, Rhinoviruses
- Mycoplasma pneumoniae & Corynebacterium Diptheriae (rare)

Pathophysiology:
- Infection causes mucosal inflamation & increased secretions affecting larynx, tracheal &
bronchi
- Oedema of subglottic area causes critical narrowing of tracheal (potentially dangerous)

Clinical Features:
Symptoms Signs
Early (12 – 72 hours) Inspection
- Low grade fever - Signs of respiratory distress
- Coryzal symptoms (Runny nose, sore throat) - Tachypnea & Tachycardia
- Nasal flaring, expiratory grunting & head
Late bobbing
- Inspiratory, harsh stridor - Suprasternal, intercostal & subcostal recessions
- Barking cough (like sea lion) - Central cyanosis (severe hypoxaemia)
- Hoarseness of voice - Use of accessory muscles
- Respiratory distress (varying degree)
Auscultation
- Poor air entry (reduced breath sound)
- Expiratory rhonchi

Diagnosis:
- Croup is a clinical diagnosis. Studies show it is safe to visualise pharynx TRO acute epiglotitis,
retropharyngeal abscess etc.
- In severe croup, it is advisable to examine the pharynx under controlled conditions (eg. in the
ICU or Operation Theatre)
- Neck Radiograph is not necessary, unless the diagnosis is in doubt, eg. TRO foreign body.
170
Assessment of severity:
- Severity from Clinical Assessment of Croup (Wagener)
- Mild : Stridor with excitement or at rest, with no respiratory distress
- Moderate : Stridor at rest with intercostal, subcostal or sternal recession
- Severe : Stridor at rest with marked recession, decreased air entry & altered consciousness
- Pulse oximetry is helpful but not essential
- Arterial blood gas is not helpful as blood parameters may remain normal to the late stage. The
process of blood taking may distress the child.

Investigation:
Blood - FBC (WBC: lymphocytosis)
- ESR (inflammation)
Pulse oximetry - To measure the oxygen saturation (< 93% considered severe)
Neck radiography - Steeple sign (Laryngeal air column narrowing below vocal cord)
Laryngoscopy - Only perform TRO peritonsillar abscess (quinsy)

Management:
- Children with viral croup can be managed at home/ hospital
- Factors to be considered for home management:
- Mild cases (mother should observe closely for signs of increased
severity)
- Time of the day
- Ease of access to hospital
- Age of the child (Low threshold for child <12 months of age)
- Parental understanding & confidence about the disease
- Indications for hospital admission:
Anteroposterior radiograph of
- Moderate and severe viral croup upper airway with croup. The
- Age less than 6 months subglottic tracheal narrowing
produces an inverted V-shape
- Poor oral intake known as Steeple sign.
- Toxic, sick appearance.
- Family lives a long distance from hospital; lacks reliable transport
- Decision to intubate under controlled conditions (in OT/ICU, with standby for tracheostomy) is
based on clinical criteria, often from increasing respiratory distress
- Indications for oxygen therapy include:
- Severe viral croup
- Percutaneous SaO2 <93%
* With oxygen therapy, SaO2 may be normal despite progressive respiratory failure and high PaCO2,
hence clicnical assessment is most important
- Antibiotics are not recommended unless bacterial super-infection is strongly suspected or
patient is very ill. IV fluids are not usually necessary except for those unable to drink.

Basic management of acute upper airways obstruction:


- Do not examine the throat!
- Reduce anxiety by being calm, confident and well organised.
- Observe carefully for signs of hypoxia or deterioration.
- If severe, administer nebulised epinephrine (adrenaline) and contact an anaesthetist.
- If respiratory failure develops from increasing airways obstruction, exhaustion or secretions blocking
the airway, urgent tracheal intubation is required.

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Treatment:
- Algorithm for the Management of Viral Croup

- Sustained action of steroids combined with the quick action of adrenaline may reduce the rate of
intubation from 3% to nil.
- Antibiotics are not recommended unless bacterial super-infection is strongly suspected or patient is
very ill.
- IV fluids are not usually necessary except for those unable to drink

Spasmodic / Recurrent Croup


- Quite common upper respiratory tract obstruction after viral croup
- Pathophysiology: Hyper-reactive upper airway
- Clinical features: Similar to viral croup WITHOUT preceding symptoms (fever & coryza)
- Complication: Asthma & other atopic diseases (eg, Rhinitis, eczema)
- Management: Similar to viral croup

Bacterial Tracheitis (Pseudomembranous Croup)


- Epidemiology (rare but dangerous)
- Aetiology:
- Staphylococcus aureus
- Haemophilus influenza
- Clinical features: Similar to viral croup except for some features
- Difference from viral croup:
Symptoms Signs
- High-grade fever - Copious thick secretions found during tracheal
- Toxic looking child intubation
- Rapidly progressive airways obstruction

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Acute Epiglottitis

Introduction:
- Acute inflammation of the epiglottis & surrounding structures (aryepiglottic fold & arytenoid
soft tissue)
- Life threatening emergency case (high risk of respiratory obstruction)
- 99% decreased in incidence since the introduction of HiB immunization
- Affects all age group but most common in children 1-6 years of age

Aetiology:
- Haemophilus influenza type b Epiglottitis triads:
- Group A, B and C Streptococci - Severe sore throat with
- Streptococcus pneumoniae dysphagia/drooling
- Klebsiella pneumoniae - Hoarse voice
- Staphylococcus aureus - Pyrexia, generally unwell,
- Haemophilus parainfluenza dehydrated

Pathophysiology:
- Infective agents invade the epiglottis causing inflammation
- Bacteria invade directly into the loosely attached submucosa membrane and might followed
by bacteremia
- Result in oedema of epiglottis and surrounding tissues, leading to airway obstruction

Clinical features:
- Important to differentiate from viral croup as it requires quite different management
Symptoms Signs
Onset is very acute General
- High grade fever - Ill and toxic looking child
- Difficult to speak and swallow - Child sit immobile, upright & open mouth to
- Drooling of saliva optimize the airway
- Noisy breathing (soft inspiratory & expiratory - Stridor is a late sign
stridor)
- Followed by SOB over hours Examination
- No throat examination with spatula until
Uncommon presentation resuscitation equipment is ready
- Cough (minimal/ absence)

Diagnosis:
- Established on the basis of the clinical history & sign of toxicemia & upper airway obstruction
- Mortality is high if the diagnosis is delayed

Investigations:
- Notify senior anesthetist, pediatrician & ENT surgeon
- Perform laryngoscopy to diagnose in ICU/ OT
- Clinical features: Cherry red, intense swelling of epiglottis & surrounding tissues
- Intubate the child before obstruction occurs
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- Blood investigation
- Blood C & S (only after the airway has been secured)
- Neck X-ray is not recommended, may precipitate total airway obstruction and death

Management:
- Admit child to the hospital urgently
- Child should be transferred to ICU or anesthetist room + senior medical stuff in case respiratory
obstruction occurs
- Require either tracheostomy / endotracheal intubation in general anesthetic
- Administered high flow humidified oxygen saturation to achieve maximal alveoli O2 saturation
- Monitor any respiratory and cardiac problem
- The patient should be supervised all time by the medical staff

Medical Treatment:
- IV antibiotic started right after the diagnosis and patent airway
- Second/ third generation cephalosporin (Ceftriaxone, Cefotaxime)
- Given for 2-5 days
- Add Flucloxacillin if the cause is Staphylococcal LTB
- Tracheal tube is usually removed after 24 hours
- Longer if the causative agent is Staphylococcus LTB

Prognosis:
- Usually resolve after 2-3 days of treatment

Prevention:
- Prophylactic rifampicin for close household contacts

Difference between acute epiglottitis and viral croup


Acute epiglottitis Viral croup
Organism H. influenza type b Parainfluenza virus
Site of obstruction Supraglottic Subglottic
Age 2-6 years old <3 years old
Onset Over hours Over days
Appearance Toxic, ill looking Unwell, toxic if tracheitis
Preceding coryza No Yes
Fever > 38.5oc < 38.5oc
Cough Absence/ slight Severe, barking
Dysphagia Present Absence
Able to drink No Yes
Stridor Soft, whispering Harsh, rasping
Voice, cry Muffled, reluctant to speak Hoarse
Drooling of saliva Yes No
Sitting-up or arching posture Yes No
Trismus/ Lockjaw Yes (deep neck space infection) No
Neck X-Ray (AP) Normal Steeple sign
Neck X-Ray (Lateral) Thumb sign Normal
Response to Adrenaline No response Very good
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Acute Bronchiolitis

Introduction:
- Commonest serious lower respiratory tract infection of infant (<2 years old)
Epidemiology:
- 2-3 % of all infants are admitted to the ward each year (annual winter epidemics)
- 90% aged 1-18 months (rare after 1 year old)
- Aged affected 1-2 years, Peak incidence is 1-6 months
Aetiology:
Virus Bacteria
- Respiratory syncytial virus (RSV) - Chlamydia trachomatis
- Adenovirus
- Rhinovirus
- Myxovirus
- Human Metapneumovirus

Risk Factors:
- Preterm Infants (who develop bronchopulmonary dysplasia)
- Congenital heart disease
Protective factors:
- Breastfeeding
- Parental avoidance of smoking
Clinical Features:
Symptoms Signs
Early General
- Coryzal symptoms (nasal congestion & - Sharp & dry cough
discharges, mild cough) - Tachycardia
- Low grade fever (<38. 5 ˚C) - Cyanosis or pallor
Inspection
Late
- Tachypnoea
- Persistent cough (chesty cough as children
- Subcostal & Intercostals recession
like to swallow sputum, may last for ≥14 days)
- Nasal flaring (when the nostrils enlarge
- SOB/ rapid breathing
during breathing) and grunting
- Noisy breathing (wheezing) - about 7 days
- Difficulty feeding related to nasal congestion Percussion
& rapid breathing which can results in - Hyperinflated chest
dehydration - Displaced liver (up to 2 cm or >6th
- Apnea intercostal space in midclavicular line)
(A pause in breathing for >15/ 20 seconds) -↓Cardiac & liver dullness
can be the first sign of bronchiolitis in an - Prominent sternum
infant. (More commonly premature baby & Auscultation
infants <2 months) - ↓air entry
- Fine end-inspiratory crepitation
- High-pitched wheezes/ rhonchi
(expiratory > inspiratory)
- Prolonged expiration

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Complications
- Recurrent apnoea
- Asthma (20-30% of patients)
- RSV specific IgE is produced in the nasopharynx
- Magnitude related to number of wheezing episodes
- Bronchiolitis obliterans (rare)
- Permanent damage to the airways
- Mostly associated with adenovirus infection rather than RSV

Differential diagnosis:
- Bronchopneumonia
- Asthma
- Cardiac Failure

Investigations:
Blood - FBC (evidence of bacteria infection)
- Pulse Oximetry (SaO2)
- ABG (only in severe cases)
-↓PaO2 &↑PaCO2
Imaging CXR
- Evidence of hyperinflation
- Anterior > 6 ribs or posterior >7 ribs in the midclavicular line
- Flattening of diaphragm
- Horizontal ribs
- Increased hilar bronchial markings
- Occasional scattered area of consolidation/segmental collapse due to atelectasis
Others - Nasopharyngeal secretion
- Demonstrating binding of immunofluorescent antibody

* The diagnosis of bronchiolitis is based upon a history and physical examination. Blood tests and CXR are
not usually necessary

Management:
Supportive (Non-Pharmacological) Pharmacological
- Humidified O2 (concentration is determined - Nebulized bronchodilators (eg. salbutamol or
by pulse oximetry which maintained >93%) ipratropium bromide)
- By nasal prong or headbox - Often used even though not shown to reduce
- Mechanical ventilation (2% of infants) severity & duration of illness

- IV drips - Fever control (acetaminophen, PCM, ibuprofen)


- Child with feeding difficulty, tachypnoea &
dehydrated - Antibiotic Rx (not recommended)
- Child on nebulizer (NG feeding maybe useful - Only in suspected secondary bacterial infection &
in these children who refuse to feed and also possibility of septicaemia
to empty dilated stomach) - Recurrent apnoea and circulatory impairment
- Acute clinical deterioration
- Monitor the child for apnea (especially in - High white cell count
infants <4 months old) - Progressive infiltrative changes on CXR

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- Monitor patient with pulse oximetry - Antiviral Rx (eg. Ribavirin)
(look for signs of worsening condition) - Indications:
- Tachycardia - Pre- existing cardiorespiratory distress
- Tachypnoea - Immunodeficiency
- Increased O2 requirement - Only maginally shortens the viral excretion &
clinical symptoms
- Encourage fluids

- Limit direct sick contact

- Influenza virus vaccination for >6mths old


especially for household contact of children,
out of home caregivers of children <5 years

* Mist, antibiotics & steroid are not helpful in acute bronchiolitis

- Cough medicines, decongestants and sedatives, are not recommended. Cough medicines and
decongestants have not been proven to be helpful, and sedatives can mask symptoms of low blood
oxygen and difficulty breathing.
- Coughing is one way for the body to clear the lungs, and normally does not need to be treated. As
the lungs heal, coughing caused by the virus resolves. Smoking in the home or around the child
should be avoided because it can worsen a child's cough. The child should be kept out of
daycare or school until the fever and runny nose have resolved (eg. the time during which they are
most contagious).

Prognosis:
- Overall is good (90% will discharge well); most infants improve within 2-5 days, recover from
acute infection within 2 weeks
- Wheezing may last for 3-4 weeks
- 50% will have recurrent episodes of cough & wheeze over the next 3-5 years

Prevention:
- Monoclonal antibody of RSV
- IM injection monthly
- reduces the number of hospital admissions in high-risk infants (mainly preterm)
- Very expensive thus limited its usage in hospital

Sign of progressive hypoxia:


- ↑Dyspnoea → Restless → Cyanosis → ↓Respiratory effort → Finally apnoea
- ↓PO2 ,↑PCO2

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Differences between acute bronchiolitis, asthma & pneumonia:
Features Bronchiolitis Asthma Pneumonia

Age - Mostly infants <2 yrs old - Older children - Any age
Aetiology Virus Allergens Bacteria
Risk Factors - Pre-term infants - Family history of asthma - Immunodeficiency
- Congenital heart disease - URTI triggers (eg. Down`s syndrome)
- Atopy - Sick contact
- Weather
- Exercise-induced
Pathophysiology Inflammation of small Affects mainly airway. Lung infection.
airway. Particularly from Particularly from Mostly affect alveoli.
bronchioles onwards as bronchioles onwards as Some of the alveoli can
cartilages are replaced by cartilages are replaced by function, some can`t.
plaques. When part of the plaques. When part of the Hence there is a rapid
airway is partially or airway is collapsed, air breathing to enhance
completely blocked, trapping remains in the gaseous exchange at
wheezing occurs and air alveoli. those functional alveoli.
trapping remains in the
alveoli.
History - Happy wheezer - Shortness of breath - Appeared sicker, more
- Coryzal symptoms - Wheezing irritable.
- Low grade fever - Unable to speak in - Coryzal symptoms
- Shortness of breath complete sentence/ - High grade fever
- Wheezing words(normally no fever) - Loss of appetite
- Wheezing
Physical - Active expiration (due to - Active expiration - Shallow and rapid
Findings indrawing of stomach breathing
wall muscles to expel the
air out)
Chest - Labored breathing - Hyperinflated chest - Reduced on affected
Movements - Hyperinflated chest (air trapping) side
- Chest wall recession - Chest wall retraction
- Use of accessory muscle

Hyperresonant Hyperresonant Dull


Percussion

Auscultation - Fine end inspiratory - Wheezing - Bronchial breathing


crackles in all zones - Prolonged expiratory - Coarse crackles
- Wheeze may or may not phase
present
- Prolonged expiratory
phase

Treatment Supportive treatment Asthma action plan Antibiotic


Reliever, preventer
* The effort required to breathe faster and harder is tiring. In severe cases, a child may not be able to
continue to breathe on his or her own.

178
Bronchial Asthma
Prof. Dr. Lucy Lum Chai See, MBBS(UM), MRCP(UK)

Definition:
- Chronic airway inflammation
- Leading to increase airway responsiveness that leads to: (Clinical triads in bolds)
- Recurrent episodes of wheezing
- Breathlessness (SOB)
- Coughing particularly at night or early morning (morning dip)
- Chest tightness
- Average daily diurnal PEF variability is >13% in children (>10% in adults)
- Often associated with widespread but variable and reversible airflow obstruction
either spontaneously or with treatment
- Physiological triad:
- Reversible bronchiolar muscle spasm
- Mucosal edema
-↑mucous production

Epidemiology:
- Most common chronic respiratory disorder in childhood
- Male : Female = 2:1 (In adult: Female > Male)
- Prevalence of asthma seems to have plateaued in Malaysia with 5.8% of children aged 6-7 years
and 8.9% of children aged 13-14% years.
- NHMS 2006 reported an asthma prevalence of 7.14% in children up to age of 18 years
- Prevalence is higher among urban and inner-city children eg. 7.3% (Muar) to 13.9% (KL)
- Responsible for 10-20% of acute admission in children aged 1-16 years
- Appear to have been a significant ↑in the incidence of asthma over the last 30 years

Aetiology: (multifactorial and complex)


Extrinsic (Atopic) Intrinsic (Non-atopic)
- Allergens (house dust mites, animal with fur, - Genetic factor (incidence is higher in child when
cockroaches, pollen, mold, perfume) first degree relatives who are asthmatic)
- Environment (smoking, pollen, carpet, toy, - Gene linkages mediates
moving to new home) i) Switch to IgE production
- Infections (respiratory viral infection) ii) Differentiation into T-helper cells (with
- Weather (cold) production of IL-4 & IL- 5)
- Exercises iii) Eosinophil production & recruitment to lung
- Emotional expression (laugh, cry, sad,
excited, stress)
- Pharmacological (aspirin, beta blocker)
- Food (additives and preservatives)
- Occupational or chemical irritants
(glutaraldehyde)
*Atopy: Individuals who readily develop antibodies of IgE class against common environmental antigens)
Hygiene hypothesis proposed that ↓ infection in the early life bias the immune system toward allergic
phenotypes and autoimmune disease. T lymphocytes may differentiate into 2 distinct subsets Th 1 & Th 2. In
infancy, a shift occurs from the in utero Th2 bias towards a Th1 response necessary for fighting viral & bacterial
infection. A reduction in childhood infection favors persistent of a Th2 bias (characterized by cytokines L IL
4,5,13) directing the immune system toward allergy type of response. However, RSV appears to ↑ the risk of
developing asthma and the validity of this hypothesis.

179
Pathophysiology:
Trigger factor

Airway muscle Mucosal Oedema (swollen


Mucus production bronchial membrane)
tightening

Narrow breathing passage

Wheezing, Cough, Shortness of Breath

Pathogenesis:
- Very complex & NOT fully understood
- Involves a number of cells, mediators, nerves & vascular leakage which can be activated by
- Several mechanisms (commonest is exposure to allergens)
- Cellular components of inflammatory response (eg. eosinophils, T lymphocytes, macrophages
& mast cells)

1) Acute phase (due to variety of stimuli)


- Onset in minutes
- Type 1 hypersensitivity immune response mediated by IgE
(mast cell degranulation = union of allergen with IgE antibodies which is bound to mast cell surface)
- Histamine & leukotriene release from mast cell
- Increase airway receptor hyperresponsiveness (vagal reflex)
- As a result of bronchospasm → narrowing and shortening of airway

2) Late phase
- Onset 4-6 hours, lasted up to 10 days
- Mast cell & alveolar macrophage release leukotriene, prostaglandin, thromboxane →
bronchoconstriction
- Chemotactic factor attracting the neutrophils, eosinophils & macrophages migration & platelet
activating factor → inflammation & edema of airway.
- Chronic changes: damage to respiratory tract epithelium → increase bronchial hyperresponsiveness
& smooth muscle hypertrophy, maintain by releasing bronchoconstrictor factor, or by local axon
reflexes thru exposed nerve fibres, lasting for days or weeks. With increasing severity & chronicity,
remodeling of the airways occurs, leading to fibrosis of the wall, fixed narrowing of the airway and a
reduced response to the bronchodilator medication.

Classification:
Intrinsic (Non-Atopic) Extrinsic (Atopic)
- Identified by bronchoprovocation test - Identified by positive skin prick test to
- Usually adulthood onset common allergens
* Less often used as all asthmatic patients show some degree of atopy

180
Clinical features:
- May have multifactorial trigger factors
Symptoms Signs
Recurrent, episodic, diurnal pattern: Inspection
- Cough (nocturnal cough & early morning - Altered consciousness
exacerbation) - Respiratory distress
- Wheezing - Cyanosed
- Shortness of Breath - Dry skin, eczema
- Chest tightness - Percentile of weight & height↓
- Interval symptoms - BCG scar
- Response to asthma therapy - Mouth- oral candidiasis due to steroid puff
- Severity (no.of school missed, limitation of - Cushing features due to prolonged usage of
activity: eat, talk, walk, hx of nebulizer, steroid, myopathy, vocal cord paralysis
gas/puff) - Hyperinflated chest
(barrel-shaped or pectus carinatum)
- Recurrent chest infections - Harrison`s sulcus (anterolateral depression of
- Failure to thrive thorax at insertion of diaphragm, best seen on
sitting)
History of atopy: - Spine (asthma causes sclerosis & kyphosis)
- Eczema or dermatitis
- Allergic rhinitis(hay fever,early morning sniff) Palpation
- Allergic conjunctivitis, urticarial & - CO2 retention (warm periphery, bounding
angioedema, food & drug allergies pulse)
(absence of these conditions does not -↓chest movement
exclude the diagnosis) -↓vocal fremitus
- Family history of atopy -↑AP diameter (hyperinflated chest)

Percussion
Hyperresonance to percussion (displace liver >6
intercostal space- palpable liver, loss of cardiac
and liver dullness)

Auscultation
- Diminished air entry
- Vesicular breathing with prolonged expiratory
phase
- Generalized expiratory rhonchi
- Crepitations (In infants)
- Silent chest

* Signs of respiratory distress (nasal flaring, expiratory grunting, head bobbing, tachypnea,
suprasternal, supra-clavicular, intercostal & subcostal recession
(Presence of recession without tachypnea = in distress; Presence of tachypnea only = in distress)
* Presence of pulsus paradoxus (↓SBP >10mmHg when inspire: acute severe asthma, chronic obstructive
lung disease, pericarditis, cardiac tamponade) and silent chest indicates acute severe asthma

Diagnosis:
- Diagnosing asthma in preschool children is often difficult. Approximately half of all children
wheeze at some time during first 3 years of life.

181
A) Transient early wheezing (Episodic)
- Virus associated wheeze, episodic viral wheeze, wheezy bronchiolitis
- Due to small airways narrowing & obstruction 2` to inflammation & immune response to viral
infection
- Episodic nature, being triggered by viruses that cause common cold
-↓lung function from birth, from small airway diameter
- Risk factor: maternal smoking during/after pregnancy & prematurity
- Female, resolves by 5 years of age dt ↑ airway size
- Well between episodes, only wheeze with viral infections

B) Persistent & recurrent wheezing (Multi-trigger)


- Preschool & school age have frequent wheeze triggered by many stimuli, discrete
exacerbations and symptoms in between these episodes
- Presence of IgE & eosinophils to common inhalant allergens is a/w persistence of wheezing
- `atopy asthma` - positive skin prick test/ IgE blood test
- Associate with eczema, rhinoconjunctivitis , food allergy, family history
- Sensitization to poorly & later to inhaled
- Inhalant allegens sensitization before & high exposure before 3 years old

C) Childhood asthma
- Clinical index to define risk of asthma in young children with recurrent wheeze
- Positive index children have 65% chance becoming asthmatic by 6 years old
- Negative index children have 95% not becoming asthmatic by 6 years old

Positive index (>3 wheezing episodes/year during first 3 years) + 1 Major criteria or 2 Minor criterias
Major criteria Minor criteria
- Eczema - Positive skin test
- Parental asthma - Wheezing without URTI
- Positive aoeroallergen skin test - Eosinophilia (>4%)

Differential diagnosis: (clinical conditions to consider)


- Bronchiolitis
- Pneumonia
- Transient early wheeze
- Non-atopic wheezing (following viral lower respiratory infection)
- Atopic asthma (recurrent wheezing, eczema, +ve family hx of allergy/ atopy)
- Cardiac failure
- Bronchiectasis Notes:
- Viral-induced wheeze is a clinical diagnosis
- Inhaled foreign body
- Infantile ashtma is diagnosed by recurrent
- Aspiration of feeds (neuromuscular disorder) episodes of wheezing with family history of
- Cystic fibrosis asthma in <12 months infants and multiple
- Chronic lung disease/ bronchopulmonary dysplasia admission (1st admission usually due to
- Eosinophilia in rhonchi patient (Ascaris acute bronchiolitis). Wheezing is not
necessary triggered by URTI but any
lumbricoides)
allergens or strong family history of asthma.
- Recurrent anaphylaxis in a child (food allergy) Cigarettes are allergens on clothes which can
- Vascular ring, laryngeal webs trigger infantile asthma if they are sensitive.
- Recurrent cough due to GERD - For asthma, peak flow & reversibility are
- Immunodeficiency needed for 5-8 years old
- If <5 years old, not need to mention PEFR.
- Tuberculosis
182
Complications of Asthma:
- Pneumonia
- Lung collapse
- Pneumothorax
- Type I respiratory failure
Investigation:
- Diagnosis is based on good history and physical examination, investigations are not usually
necessary.
- Bronchodilator reversibility in PEF >13% or FEV1 >12% is supportive of asthma diagnosis (may
not present in mild asthmatics)
- Raised exhaled nitric oxide and postivie skin prick tests to aeroallergens.
- CXR (only when suspecting):
- Mediastina mass (lymphoma, malignant tumor that compresses bronchioles)
- Pneumothorax (when not responding to bronchodilator, Cx of asthma)
- DO NOT do chest X-ray unless patient is on distress
- TRO other differential diagnosis:
- HRCT thorax scan, lung function test, 24-hour pH study, immune function tests, sweat test,
bronchoscopy, echocardiogram & Mantoux testing

Evaluation of newly diagnosed asthma:


Intermittent Asthma
- Daytime symptoms <1/week
- Nocturnal symptoms ≤2/month
- No exercise-induced sypmtoms
- Brief exacerbations not affecting sleep and activity
Persistent Asthma
Mild - Daytime symptoms ≥1/week
- Nocturnal symptoms >2/month
- PEFR or FEV1 >80%
- Exercise or activity-induced asthma
Moderate - Daytime symptoms daily
- Nocturnal symptoms >1/week
- Exacerbation affecting sleep & activity ≥2/month
- PEFR or FEV1 60-80%
- Exercise or activity-induced asthma
Severe - Daily symptoms
- Daily nocturnal symptoms
- Exacerbation affecting sleep & activity frequently
- PEFR or FEV1 <60%
- Exercise or activity-induced asthma

Evaluation of asthma control:


Characteristic Well controlled Partially controlled Uncontrolled
Daytime symptoms None (≤2/week) >2/week ≥3 features of
Nocturnal symptoms None Any partially controlled
Activity limitation None Any asthma present in
Need reliever/Rescue Tx None (≤2/week) ≥2/week any week
Lung function (PEF/FEV1) Normal <80%
(predicted/personal best)
Exacerbation None ≥1/year
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Assessment of severity of acute asthma exacerbation (AEBA) for children:
Parameters Mild Moderate Severe Life-threatening
Breathless When walking When walking At rest Apnoea
(Infant: feeding (Infant: stop
difficulties) feeding)
Talks in Sentences Phrases Words Unable to speak
Alertness May be agitated Agitated Agitated Drowsy/confused/
coma
Respiratory rate Normal to mildly Increased Markedly Poor respiratory
increased increased effort
Accessory Absent Present Present Paradoxical
muscle/retractions thorocoabdominal
movement
Wheeze Present Present Present Silent chest
SPO2 (on air) >95% 92-95% <92% Cyanosis & <92%
Pulse rate Normal Increased Increased Bradycardia
PEFR (after initial >80% 60-80% <60% Unable to perform
bronchodilator, %
predicted or
personal best)

Management Plan:
- Assess asthma severity/ newly diagnosed asthma
- Choose preventer treatment (refer next page: Algorithm for long term management of asthma)
- Assess asthma control in 4-8 weeks (refer previous page: Evaluation of asthma control)
- Stepwise medication (refer next page: Algorithm for long term management of asthma)
- Monitor asthma control (refer previous page: Evaluation of asthma control)
* For any level, check compliance, technique & trigger factors

Inhaler devices recommended for different age:


<2 years (Infant) : Oral corticosteroid
<5 years : Oral corticosteroid, MDI + Spacer (Aerochamber)
5-8 years : MDI + Aerochamber
>8 years : MDI + Aerochamber + Mask on dry powder inhaler (>11 years old)
Acute asthma (better after oxygenation)
- Close monitoring for at least 4 hours
- Vital sign, Color, Oxygen (pulse oximetry), ABG, PEFR
- Oxygenation (nebulizer)
- Hydration (maintenance fluid)
- Role of aminophylline (Bronchodilator)
- Antibioitic if suspected infection (not in AEBA 2` to pneumonia which is mostly viral)
- Avoid sedative, mucolytic agents
- On discharge, provide asthma action plan to assist parents/patients
- How to recognize worsening asthma
- How to treat worsening asthma
- How and When to seek medical attention
Severe asthma (not better with oxygenation)
- Signs: cyanosed, altered consciousness, silent chest, SPO2 < 95%
- Mx: Same with acute asthma
184

Algorithm for Long-term Management of Asthma: Algorithm for Acute Exacerbation of Asthma in Children:

185
How to use Aerochamber:
- Shake the inhaler
- Remove the cap of inhaler
- Connect inhaler with mask spacer
- Mask spacer fully cover the mouth and nose (no gap)
- Press the inhaler to spray 1 puff of medication into it
- Ask patient hold for 20 seconds, count 10 valve flip (if valve
flip does not function, count chest expansion for 10 times)
How to clean Aerochamber:
- Rinse with water
- Do not brush (prevent electrostatic that causes particles of medications to attach to the wall
of Aerochamber and not entering patient`s airway)
- Dry in rain (not sun)

High risk asthma group:


- Poor asthma control
- Require >3 medications to control
- Excessive reliance on bronchodilators
- Frequent nocturnal attacks and sleep disturbances
- Inadequate treatment or poor adherence
- Frequent visits to ED for asthma exercerbations
- Previous ICU/HDU admission
- Denial of ashtma as a problem
- Failure to perceive severe symptoms of asthma
especially adolescent
- Immediate asthma symptom reaction/hypersensitivity
following certain food, drugs or allergen.

Ashtma Action Plan


- Written action plan details, for individual patient,
daily management (medications & environmental
control strategies), how to recognise and handle
worsening asthma.
- Recommend for patients who have moderate or
severe asthma, history of severe exercerbation,
poorly controlled asthma.
- Usually symptom based but in older children
peak flow measurements may be used as well.
- Should have following components:
- Recommended doses & frequencies of daily
medication
- How to adjust medicatonc at home in response
to particular signs, symptoms, peak flow value
- Symptoms indicating the need for closer
monitoring or acute care
- Emergency telephone no. for doctors, ED, rapid
transportation,family/friends for support
- List of triggers that may cause asthma attack,
help inform others & patient of what triggers to
avoid
- PEF monitoring is recommended for moderate
to severe asthma

186
Pneumonia
Prof. Dr. Lucy Lum Chai See, MBBS(UM), MRCP(UK)

Definition:
- Infection of the lung parenchyma
- Infiltration of the interstitial tissue with inflammatory cells

Epidemiology:
- Incidence rate - Highest in infancy
- Remains relatively high in childhood
- Low in adult
- Increases again in old age

For younger child : Virus is the most common


For older child : Bacteria are the most common
It is difficult to distinguish btw virus and bacteria pneumonia in clinical practice

Classification: (by both anatomically & etiology)


Anatomy (CXR) Etiology
A) Lobar pneumonia A) Community-acquired pneumonia
- Affects the whole of one lobe
B) Nosocomial pneumonia
- Lobar consolidation
B) Bronchopneumonia C) Aspiration pneumonia
- Affects bronchi & lobules
* Useful if divided by age of the infants,can guide
- Localised or generalized patch infiltration
management

Aetiology:
Newborn Infancy Older children/Adult
- Bacteria from mother`s genital - Mostly viral, particularly RSV - Viral infection is rare
tract, usually during (preterm infants) - Bacteria are more common
intrapartum
- Group B β-hemolytic - RSV - Mycoplasma pneumoniae
streptococcus - Streptococcus pneumoniae - Streptococcus pneumoniae
- E.coli - Haemophilus influenzae - Chlamydia pneumoniae
- Gram -ve bacilli/ enterococci - Bordetella pertussis - Mycoplasma tuberculosis
- Proteus - Chlamydia trachomatis
- Klebsiella - Staphylococcus aureus Others:
- Listeria (most severe, a/w malnutrition) - Chlamydia psittaci
- Coxiella burnetti
- Legionella pneumophila
1-3 months Erythromycin
<1 month Penicillin, >5 years old Erythromycin +
Gentamycin 3 months - Ampicillin + Cloxa Ampicillin
5 years old /Augmentin
Aspiration pneumonia : Enteric gram -ve bacteria +/- Strep Pneumoniae, S. Aureus
Immunocompromised : Bacterial (Pneumocystis jiroveci, TB)
Viral (CMV, VZV, HSV, Measles, Adenovirus)
Fungi (Aspergillus, Candica, Histoplasma)

187
Clinical Features:
Symptoms Signs
- Fever Inspection
- Cough (sometimes with sputum production in - Grunting, air hunger, tachypnea, toxic-looking,
older children) cyanosis, nasal flaring, head retracted, recession
- Breathlessness (intercoastal, subcoastal, supraclavicular)
- Rapid & SHALLOW breathing (impression that a
child is afraid to breath deeply) Palpation
- Runny nose ↓Chest movements
- Lethargy ↑tactile fremitus
- Restless, Agitated, Irritated
Percussion
- Pleural inflammation Maybe
Dull to percussion
- Pleuritic chest pain (worsen on inspiration) absent in
- Neck stiffness (involve upper lobe) Auscultation infants
- Abdominal pain (involve lower lobe) - ↓breath sounds
- Bronchial breath sounds
- Coarse crepitations
- Pleural rub
-↑vocal fremitus

Complications:
- Parapneumonic effusion
- Empyema (infected pleural effusion)
- Usually associate with Pneumococcus (childhood)
(For adults: penicillin resistant S.aureus, gram-ve bacteria & anaerobic bacteria)
- Rx : drainage by intercostal chest drain or surgery
- Septicaemia
- Lung abscess

Assessment of severity:
- Essential for optimal management of pneumonia
- Categorized according to mild, severe, very severe based on respiratory symptoms as shown
below:
< 2 months old 2 months - 5 years old
Mild Pneumonia - Rapid breathing -
Severe - Chest indrawing - Severe chest indrawing
Pneumonia - Rapid breathing
Very severe - Not able to drink - Not feeding
pneumonia - Convulsions - Convulsions
- Drowsiness - Abnormally sleepy or difficult to wake
- Malnutrition - Fever/low body temperature
- Hypopnea with slow irregular breathing

Investigations:
- Children with bacterial pneumonia cannot be reliably distinguished from those with viral disease on the
basis of any single parameter, clinical, laboratory or chest radiograph findings.
- Chest radiograph is indicated when clinical criteria suggest pneumonia. It will not diagnose aetiological
agent. However the chest radiograph is not always necessary if facilities are not available or the
pneumonia is mild
- If recurrent pneumonia, exclude cystic fibrosis, immunodeficiency status
188
Blood - FBC (WBC)
-↑Predominance of polymorphonuclear cells suggest bacterial cause
-↓Either suggest a viral cause or severe overwhelming infection
- Blood culture & sensitivity
Remains the non-invasive gold standard for determining the previse
aetiology of pneumonia. However the sensitivity of this test is very low.
+ve blood cultures are found only in 10% to 30% of patients with
pneumonia. Blood culture should be performed in severe pneumonia or
when there is poor response to the first line antibiotics.
Nasopharyngeal aspirate - Viral isolatoin, C&S
BUSE - Hyponatraemia (SIADH)
CXR - Lobar consolidation
- Widespread bronchopneumonia
- Cavitation (less common)
Pleural Fluid - If there is significant pleural effusion diagnostic pleural tap will be
helpful
Serology - Mycoplasma pneumoniae, Chlamydia, Legionella and Moraxella
catarrhalis are difficult organism to culture, thus serology is performed
in patients with suspected atypical pneumonia. Acute phase serum titre
more than 1:160 or paired samples taken 2-4 weeks apart showing 4
fold rise is a good indicator of Mycoplasma pneumoniae infection. This
test should be considered for children aged 5 years or older.
Pulse oximetry - Assessment of oxygenation, pulse oximetry is the best measurement
for hypoxia which avoid the need for arterial blood gases. Good
indicator for severity of pneumonia.

Recurrent pneumonia
- Max 6 admissions/year, if exceeded must further investigate
- Aspiration: GERD, Vocal cord palsy
- Immunodeficiency
- Congenital cardiac disease (ASD, VSD, PDA)
- Obstruction (lymph node, vascular ring, foreign body)
-↓mucous secretion (asthma, Cystic fibrosis)
- Lung deformity (Tetralogy of Fallot)

Management:
- Divided into supportive & pharmacological measures
- Criteria for hospitalization:
- Children aged <3 months whatever the severity of pneumonia
- Fever >38.5 `C, refusal to feed and vomiting
- Fast breathing with or without cyanosis
- Associated systemic manifestations
- Failure of previous antibiotic therapy
- Recurrent pneumonia
- Severe underlying disorders (eg. Immunodeficiency)

Community acquired pneumonia can be treated at home. It is crucial to identify indicators of


severity in children who may need admission. Failure to recognize the severity of pneumonia may
lead to death. The following indicators can be used as a guide for admission.

189
Supportive Measures:
Fluids Oral intake should cease when a child is in severe respiratory distress. In severe
pneumonia, secretion of ADH is ↑ which means that dehydration is uncommon.
It is important that the child should not be overhydrated.
Oxygen Oxygen reduces mortality a/w severe pneumonia. It should be given especially
to children who are restless, tachypnoeic with severe chest indrawing, cyanosed
or not tolerating feeds. It is important to maintain the SaO2 >95%.
Temperature The rationale to use paracetamol is only to ↓ discomfort from symptoms. The
control PCM will not abolish fever.
Chest To assist in the removal of tracheobronchial secretions. Intention is to remove
physiotherapy airway obstruction,↑gas exchange and ↓the work of breathing. There is no
evidence to suggest that chest physiotherapy should be routinely done in
pneumonia.
Cough syrup It is not recommended as it causes suppression of cough and may interfere with
airway clearance. Adverse effects and overdosage have been reported.

Pharmacological Measures:
When treating pneumonia, the clinical, laboratory and radiographic findings should be considered. Other
factors include age of the child, local epidemiology of respiratory pathogens and sensitivity of these
pathogens to particular microbial agents and the emergent of antimicrobial resistance. The severity of
the pneumonia and drug costs has also a great impact on the selection of therapy. The majority of
childhood infections are caused by viruses and do not require any antibiotic. However, it is also very
important to remember that we should be vigilant to choose appropriate antibiotics especially in the
initial treatment to reduce further mortality and morbidity.

For inpatient management of children with severe pneumonia, the following antibiotics are
recommended:
1st line : β lactam dugs : Benzylpenicillin, Amoxycillin, Ampicillin, Amoxycillin-Clavulanate
2nd line : Cephalosporins : Cefotaxime, Cefuroxime, Ceftazidime
3rd line : Carbapenem, Imipenem
Others : Aminoglycosides, Gentamicin, Amikacin

If there are no signs of recovery, patients remain toxic and ill with spiking temperature for 48-72 hours, a
second line antibiotics need to be considered. If Mycoplasma or Chlamydia species are the causative
agents, a macrolide is more appropriate. A child admitted to hospital with severe community acquired
pneumonia must receive parenteral antibiotics. As a rule, in severe cases of pneumonia, combination
therapy using a second or third generation Cephalosporins and macrolide should be given.

Predominant bacterial pathogens of children and the recommended antimicrobial agents to be used:
Pathogens (β-lactam susceptible) Antimicrobial agents
Streptococcus pnuemoniae Penicillin, Cephalosporins
Haemophilus influenzae type b Ampicillin, Chloramphenicol, Cephalosporins
Staphylocccus aureus Cloxacillin
Group A Streptococcus Penicillin, Cephalosporin
Mycoplasma pneumoniae
Chlamydia pneumoniae Macrolides such as erythromycin and azithromycin
Bordetella pertussis

In children with mild pneumonia, their breathing is fast but there is indrawing of chest, antibiotics can be
prescribed orally in outpatient. The mother is advised to return in 2 days for reassessment or earlier if the
child is getting worse.
190
Viral Infection
- Primary viral pneumonia tends to be more insidious onset, less toxic and dyspnoeic
- CXR are much less impressive than bacteria pneumonia
- Radiological features tend to show a more fluffy or patchy appearance often radiated from 1 or
both hilar region.
- Usually bronchopneumonia but lobar pneumonia is still possible
- Treatment is mainstay supportive (antibiotic therapy is indicated when there is fever)

Staphylococcal infection
- Staphylococcus aureus (S.aureus) responsible for a small proportion of acute respiratory
infections in children (common in infant). Nevertheless a high index of suspicion is required
because of the potential for rapid deterioration. It is chiefly a disease of infants and has a
significant mortality rate.
- Radiological features include the presence of multilobar consolidation, cavitations,
pneumatocoeles (tension cysts), spontaneous pneumothorax, empyema and pleural effusion.
- Treatment with high dose Cloxacillin (200mg/kg/day) for a longer duration and drainage of
empyema will result in good outcome in the majority of cases.

Mycoplasma infection
- This is a very common cause of pneumonia in child >5 years old.
- Onset is usually subacute. (1 or 2 weeks)
- Symptoms include general malaise, fever, headache, irritating and paroxysmal cough
resembling pertussis. CXR are often remarkably few and less characteristic. But one is
frequently surprised at the extent of consolidation compared with the paucity of clinical sign.
- Diagnosis is established by mycoplasma serology.
- Erythromycin is the drug of choice.

Afebrile pneumonia syndrome


- Organisms : Chlamydia trachomatis, CMV, Mycoplasma hominis, Ureaplasma urealyticum
- History of maternal STD

Chlamydia pneumoniae
- 2-19 weeks after birth
- Conjunctivitis, URTI >1 week, afebrile
- Physical findings: Crackles, occasional rhonchi, staccato cough, tachypnea
- CXR: Hyperexpanded lung & bilateral infiltrate
- Eosinophils ↑(>400/mm3, IgM, IgG)

191
Foreign Body Aspiration
Prof. Dr. Lucy Lum Chai See, MBBS(UM), MRCP(UK)

Epidemiology:
- Majority are <4 years old
- Most death 2` to foreign body aspiration occurs in this age group.
- Right mainstem bronchus takes off at a less acute angle than left mainstembronchus,
foreign bodies tend to lodge in right airways. Thus, pathology occurs more on right lung.

Clinical features:
Symptoms Signs
- Clear histories of choking, witnessed aspiration, - Cough
physical or radiographic evidence of foreign - Localized wheezing
body aspiration - Unilateral absence of breath sounds
- Most foreign bodies are small and quickly - Stridor
expelled, some remain and causes persistent - Bloody sputum (rarely)
cough, sputum production or recurrent
pneumonia.
- Suspect foreign body aspiration when:
- Persistent wheezing unresponsive to
bronchodilator therapy
- Persistent atelectasis
- Recurrent or persistent pneumonia
- Chronic cough without other explanation

Differential diagnosis:
- Oesophageal foreign bodies (can cause persistent stridor or wheezing + dysphagia)

Diagnostic studies
- Expiratory and lateral cubitus chest radiograph:
- Reveal presence of radiopaque objects & focal air trapping, especially on expiratory film
- Fluoroscopy: for children who cannot perform expiratory views
- Rigid bronchoscopy: for strong evidence of foreign body aspiration. Best for removal of
foreign body.
- Flexible bronchoscopy: Used to locate an aspirated foreign body.

Prevention of foreign body aspiration:


- Educate parents and caregivers by NOT giving children nuts, uncooked carrots/other foods
that may be easily broken into small pieces & aspirated BEFORE MOLAR TEETH eruption.
- Be aware of small objects given to small children and also accessibility of the objects.

Aspiration Pneumonia
Prof. Dr. Lucy Lum Chai See, MBBS(UM), MRCP(UK)

- Defined as the inhalation of either oropharyngeal or gastric contents into the lower airways
(act of taking foreign material into the lungs)
- For it to occur, there must be a breakdown of usual defenses that normally protect the
tracheo-bronchial tree as well as pulmonary complications that result from aspiration event
- Most commonly occurs in individuals with chronically impaired airway defense mechanisms,
such as gag reflex, coughing, ciliary movement, and immune mechanisms, all of which aid in
removing infectious material from the lower airways
- Can occur in community or in a hospital/health care facility (eg. nosocomial). In both
192
situations, anaerobic organisms alone or in combination with aerobic and/or microaerophilic
organisms play a role in the infection. In anaerobic pneumonia, the pathogenesis is related
to the large volume of aspirated anaerobes (eg, as in persons with poor dentition, poor oral
care, and periodontal disease) and to host factors (eg. alcoholism) that suppress cough,
mucociliary clearance, and phagocytic efficiency, both of which increase the bacterial
burden of oropharyngeal secretions
Clinical features:
- More rapid onset * History of last feeding is very important!
- May or may not be preceded by URTI (inhalation case)
Risk factors:

Neurological Anatomic disorders Physiological Mechanical Others


disorders disorders disruption of normal
defense barrier
- Cerebral palsy - Cleft palate - Incompetence - Instrumentation - Altered
- Meningitis - Anomalies of face cardiac sphincter like naso-gastric consciousness in
- Encephalitis and skull - Gastric outlet tube, endotracheal general
- Seizures (Goldenhar obstruction intubation or anesthesia
- Head trauma syndrome) - GERD and tracheostomy - Drug overdose
- Intracranial mass - Tracheoesopha- vomiting - Accidental
lesion geal fistula - Oropharyhgeal ingestion
- Down`ssyndrome - Scleroderma incoordination
- Myasthenia gravis - Esophageal
- Birth asphyxia diverticular
- Werdnig-Hoffman
disease
- Preterm birth

Complication (aspiration pneumonia):


- Atelectasis
- Lung abscess
- Empyema
- Pneumothorax secondary to mechanical ventilation
- Septicemia
- Shock
- Prolonged hospitalization

Chemical pneumonitis (aspiration pneumonitis and Mendelson syndrome)


- Due to the parenchymal inflammatory reaction caused by a large volume of gastric contents
independent of infection
- Aspiration of a massive amount of gastric contents can produce acute respiratory distress
within one hour. This disease occurs in people with altered levels of consciousness resulting
from seizures, cerebrovascular accident (CVA), central nervous system (CNS) mass lesions,
drug intoxication or overdose, and head trauma
- The acidity of gastric contents →chemical burns to the tracheobronchial tree involved in the
aspiration →inflammatory cellular reaction fueled by the release of potent cytokines,
particularly TNF-α, IL-8. If pH of the aspirated fluid < 2.5 and the volume of aspirate > 0.3
mL/kg of body weight (20-25 mL in adults), it has a greater potential for causing chemical
pneumonitis.
193
Pertussis (Whooping cough)

Introduction:
- Acute tracheobronchitis that begin with mild URTI symptoms followed by a severe paroxysmal
cough

Epidemiology:
- All ages are affected but 90% of cases occur in children <5 years of age
- About 70% of unimmunized children are affected by the age of 5 years old
- Highly contagious notifiable disease

Aetiology:
Bordetella pertussis : encapsulated gram -ve coccobacillus

Pathogenesis:
- Pathogen only for human
- Transmitted via airborne droplets, produced during the cough episode
- Attachment of the pili (filamentous hemaglutinin) to the cilia of the epithelial cell, decreased
cilia activity followed by death of the ciliated epithelial cells
- Pertussis toxin stimulates adenylate cyclase, then rise in cyclic AMP-dependent protein kinase
activity, causes a failure of lymphocytes to enter the lymphoid tissues, then a striking
lymphocytosis in the blood

Clinical features:
- Incubation period is 7-14 days (Oxford: 10-14 days)
- Symptoms may persist for 10-12 weeks
- Most contagious during first 2 weeks of cough
- May occur in the immunized child but it is almost invariably less severe
- In very young infant (<3 months) cough & catarrhal sp are less marked and the presentation is
only recurrent attack of apnoea & cyanosis, which increases mortality
Symptoms
Catarrhal stage (1-2 weeks)
- Coryzal symptoms (runny nose, conjunctivitis, malaise)

Paroxysmal stage (3-6 weeks, up to 3 months, 100-day cough)


- Paroxysms or spasmodic cough: series of hacking cough without taking breath in between the cough,
this pattern of cough needed to dislodge plugs of necrotic bronchial epithelial tissues & thick mucus
- Followed by characteristic inspiratory `whoop` (forced inspiration against closed glottis)
- Vomiting of the ingested food or the thick mucus (post-tussive emesis)
- Facial congestion & cyanosis
- Copious amount of mucus which flow from nose & mouth
- In severe cough: conjunctival petechiae/ subconjunctival hemorrhage & epistaxis
- Infant may not have the `whoop` but often have apnoeas following coughing spasm

Convalescent stage (1-2 weeks)


- Residual cough persists for months, especially with physical stress or respiratory irritants
- Coughing becomes less severe, paroxysms & whoop slowly disappear

Diagnosis:
- Mainly clinical, particularly if a typical paroxysmal cough & lymphocytosis
- Confirmed by isolation of B. pertussis from the patients` nasopharyngeal secretion
194
Investigation:
- per-nasal swab or sputum for culture (unsatisfactory as organisms die on the way to the lab &
slow to culture)
- Nasopharyngeal aspirates
- Agglutination/serology test (not useful for diagnosing acute infection, but convalescent
phase is confirmatory)
- Direct fluorescent antibody testing is specific but insensitive, not recommended)
- PCR (sensitive as culture but not specific)
- Blood investigation
- FBC (marked lymphocytosis >15,000 cells/mm3 or >10,000 cells/mm3)

Management:
- Admit patient to hospital if <6 months of age (risk of apnoea)
- Clearing the upper airway of mucus and O2 therapy
- Azithromycin, clarithromycin, erythromycin under 1 month age, TMX for older than 2 months
- Erythromycin to eradicate the organisms (if started during catarrhal phase, else):
- reduce the number of organism (spread) but no reduction in severity or duration of illness as
toxin has already damaged the respiratory mucosa
- risk of having side-effect: infantile hypertrophied pyloric stenosis (IHPS) -> azithromycin
- Salbutamol + corticosteroids (Oxford HOS) - ineffective

Prevention:
- Immunization reduces pertussis by 80-90% (but does not guarantee protection)
- Macrolides effective in preventing secondary cases in contacts exposed to pertussis
- Underimmunised close-contacts under 7 years of age should receive a booster dose of DTaP
(unless a booster dose has been given within preceding 3 years), whereas those 7-10 years of
age should receive Tdap.
- All close-contacts should receive prophylactic antibiotics for 5 days (azithromycin) or 7-14
days (clarithromycin or erythromycin, duration based on age)

Complications:
General - Malnutrition
CNS - Apnoea, cerebral anoxia with convulsions (young infants)
- Encephalopathy (permanent disability)
Respiratory System - Lobar pneumonia (secondary to bacterial infection, 90% of death)
- Atelectasis, Bronchiectasis (late) - secondary to mucosal plugs
- Pneumomediastinum, Pneumothorax
- Interstitial or subcutaneous emphysema
HEENT - Subconjunctival haemorrhage
- Periorbital petechiae
- Otitis media
- Sinusitis
Others - Rectal prlapse
(due to prolonged - Inguinal hernia
coughing fits) - Frenulum tear

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Cystic Fibrosis

Epidemiology:
- Most common serious genetic disorder of Caucasians.
- Carrier rate in Caucasians of 1 in 25, with 1 in 2500 affected births.

Aetiology:
- AR disorder arising from mutation in a gene on long arm of chromosome 7 which codes for
protein called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
- Most common mutation in 70% of cases: 3-base pair deletion that removes the phenylalanine
of position 508 (ΔF508).

Pathophysiology:
- Mutations in CFTR causes defective cAMP-dependent chloride ion transport across epithelial
cells and increases the viscosity of secretions especially in respiratory tract and exocrine gland.
- There is also abnormal transport in sweat gland epithelium resulting in high concentration of
Na and Cl in sweat

Clinical features:
Respiratory tract Abnormal ions transport aross epithelial cells

Reduced airway surface liquid layer, impaired ciliary function & retention
of mucopurulent secretion

Increases viscosity of secretion in airway

- Recurrent chest infection by:
- Staphylococcus aureus
- Haemophilus influenza
- Pseudomonas aeruginosa
- Burkholderia cepacia

- Bronchiectasis and abscess formation (bronchial wall damage)
Symptoms Signs
- Recurrent, productive cough - Clubbing, HPOA
- Copious sputum, smelly & - Hyperinflation
change in odour - Coarse inspiratory crackles
- SOB - Expiratory wheezing
- Lobar collapse, Pneumothorax
- Scoliosis, Chest scars (portacath)
Exocrine gland - Pancreatic insufficiency (deficient in lipase, amylase, protease)
↓ (low fecal elastase)
Maldigestion →Malabsorption → Malnutrition → Failure to thrive (90%)
- Diabetes Mellitus (steatorrhoea)
GIT - Meconium ileus during neonatal period (10-20%) [normal: 24-48 hrs]
- Treated with Gastrograf in enema or surgery

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- Distal intestinal obstruction syndrome (adolescent/ younger adults)
- Intussusception
- Rectal prolapse (>18 months, resolves quickly on starting CREON)
- NASH (fatty liver), cirrhosis, hepatosplenomegaly, portal hypertension
- Cholesterol gallstone, pericholangitis
Joints - Cystic fibrosis-related arthropathy (episodic, <1 week, non-erosive, large
joint involvement)
- Hyperthrophic pulmonary osteoarthropathy (HPOA)
ENT - Nasal polyps
- Sinusitis
CVS - Right-sided heart failure (late, 2` to severe lung disease)
Reproductive - Males are infertile (absent vas deferens)
- Pubertal delay

Clinical features by age groups:


Age group Clinical features
Infancy - Meconium ileus
- Prolonged neonatal jaundice
- FTT
- Recurrent chest infections
- Malabsorption, Steatorrhoea
Young child - Bronchiectasis
- Rectal prolapse
- Nasal polyps
- Sinusitis
Teenager & adults - Diabetes Mellitus (due to decreasing pancreatic endocrine function)
- Cirrhosis & Portal hypertension
- Chest infections, Pneumothorax & life-threatening haemoptysis
- Distal intestinal obstruction syndrome (viscid mucofaeculent material
obstructs bowel)
- Infertility in males (due to congenital absence of vas deferens)
- Allergic bronchopulmonary aspergillosis (ABPA)

Diagnosis & Investigations:


Sweat test - Abnormally salty sweat due to high NaCl content
(Gold standard) - Sweat Cl concentration of 60-125mmol/L repeated twice, diagnostic
of Cystic Fibrosis (CF) [Normal: 10-30mmol/L]
Immunoreactive - Screening test can be done in young infants as part of Guthrie test
trypsin (IRT) - Using dried blood, IRT will be elevated
DNA analysis - To detect gene mutation in CFTR protein
Blood - FBC (anaemia of chronic disease, infection)
- LFT (albumin for nutritional status, AST/ALT for liver derangement)
- Coagulation profile (coagulopathy secondary to liver cirrhosis)
Renal profile (BUSE) - Hyponatraemia (leads to seizure)
- Hypokalaemic alkalosis (due to loss of sodium & postasium loss)
FBS - Cystic Fibrosis-related Diabetes
Imaging - CXR (bronchial wall thickening, cystic ring shadows & Tram`s lines for
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bronchiectasis; hyperinflation with flattened diaphragm)
- CT thorax (signet`s ring shadows with honeycombing - advanced)
- AXR (meconium ileus or equivalent)
- USS (liver, gallbladder)
- ERCP (strictures, choledocholithiasis)
Stools - Low faecal elastase (signifies pancreatic insufficiency)
- Microscopy for fat globules(high fat content), absent of chymotrypsin

Management:
- Multidisciplinary (involved paediatrician, physiotherapist, dietitian, nurse, primary care team
and patient`s parents)
- Aims to ensure optimum physical & emotional growth & to delay onset of pulmonary disease:
- General growth & development
- Respiratory pathogens
- Requency & severity of chest infections & lung function
- Nutrition & GI symtoms
- Development of diabetes, liver or joint disease
- Psychosocial problems (school progress etc)
- Fertility & genetic counseling (later stage)

Respiratory Nutritional Genetic Endocrine


- Physiotherapy - High calorie diet - Genetic screening - DM (insulin)
- Chest percussion with fat soluble - To identify carrier - Reduced fertility:
- Breathing exercise vitamins (A,D,E & K) so that genetic - Obstruction &
- Postural drainage supplement counseling can be abnormal
given development of
- Prophylactic - Pancreatic enzymes vas deferens in
antibiotics supplement using male, ICSI still
enteric coated possible
- IV antibiotics for microspheres in - Subfertility in
acute exacerbation gelatin coated female (tolerate
capsules (CREON) pregnancy well
- Nebulised unless have severe
bronchiodilators lung disease)

- Oxygen at home as
disease progresses *CREON contains
amylase, lipase &
*Antibiotics should protease which have
cover S. aureus, marked effect of
H. influenza & steatorrhoea and allow
Pseudomonas sp. catch up growth
Others
- Mucolytics (eg. Dnase or hypertonic saline)
- ERCP for gallstones, Liver transplant for severe liver cirrhosis
- Heart-lung transplant or bilateral lung transplant (end-stage disease, >50% survival 10 years)
- NSAIDS/ short course corticosteriods (CF-related arthropathy/HPOA)

198
Cystic Fibrosis Long Case (Template)

The hinge of scoring a CF case is to really focus on the chief complaint, do not be narrow-minded
of the cause of respiratory diseases and got carried away by the underlying CF, come out with
differentials of current symptoms, identify current issues to be addressed and present relevant
past medical history of CF.

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A. History
Presenting complaint
Respiratory diseases Productive cough (younger children might not be able to expectorate),
SOB, reduced effort tolerance, fever
HOSPI: For each symptom, ask for duration, chronology of each happening and correlate them with
one another
Associated symptoms Onset: Acute / gradual
URTI symptoms: Runny nose, red eyes, ear discharge, sore throat, horse
crying voice
Cough: Productive or non-productive, sputum volume, colour, blood
Fever: Pattern, documented temperature, relieve with medication
Pain: Pleurisy chest pain
SOB: Cyanosis, intercostal recession, quantify reduced effort tolerance,
orthopnoea, PND
Allergens/ irritants: Wheeze, diurnal variation, precipitating factors such as
cold, fur, dust
TB symptoms: Chronic cough, night sweat, LOW, LOA, sick contact,
crowded place
Progression Progressively worsening over the past few days / years, similar or worse
than previous episodes, frequency in a month / year
Severity Disturbed sleep, poor feeding, inactivity
Past Complications Pneumothorax, moderate-to-large haemoptysis, allergic
bronchopulmonary aspergillosis (ABPA)
Past investigations Sputum colonisation, chest X-ray, pulmonary function tests, overnight
oxymetry
Home management Exercise, Chest physiotherapy (frequency, type and by whom), PEP mask;
antibiotics (nebulised/ oral/ parenteral), saline, bronchodilators,
corticosteroid; venous port access
Systemic review
Gastrointestinal disease - Rectal prolapse (feeling of something coming out during defecation, pain
upon defecation)
- Symptoms of intestinal obstruction, vomiting, abdominal pain,
constipation
Endocrinology diseases - Symptoms of DM (found to be hyperglycemic), polyuria, polydipsia,
polyphagia
- symptoms of pancreatic insufficiency, pale oily stool, poor weight gain,
failure to thrive
Joint diseases - Large joint pain
CVS diseases - Palpitation
Reproductive system - Breast pubic hair and external genitalia maturation delay
Past medical history
Diagnosis Initial symptoms, investigations and management prior to diagnosis,
diagnosis (when, where, how)
Progression Hospitalisation details (frequency, duration, usual treatment)
Complications Frequent respiratory disease
Antibiotic resistant infection
Venous port: thrombosis, infection, haemorrhage, embolism, loss of
venous access and needle phobia
Follow up Outpatient clinics attended (where, how often, routine tests performed:
weight, nutrition, sputum, spirometry, OGTT, LFT, pancreatic function test,
HRCT )

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Gestational history
Antenatal diagnosis Antenatal diagnosis of child with CF with known parental genetic status/
previous CF siblings
Birth history
Complications Perinatal meconium ileus
Developmental milestone
Developmental delay Motor developmental delay due to failure to thrive (poor bone and muscle
growth)
School performance, slow learner
Drug history
What drug Types and purpose, traditional/ self-prescribed medicine
Compliance Is the patient compliant, can patient take the drug by self, if not aided by
who
Side effects Long term oral steroid: HPT, central obesity, easy bruising
Allergies
Vaccination
Schedule vaccination up to date or ever halted due to infection episodes ; when is
the next vaccination due; early measles immunisation
Extra immunisation pneumococcal, influenza vaccines, gamma-globulin for measles contacts,
yearly influenza vaccine
Allergy history
Allergies to food or drug. Presentations of allergies. Management of
allergies (desensitization)
Diet history
Sufficient calorie intake Quantity of milk per feed, frequency of feeds per day, formula or breast
(CF patient need 120% of milk, high energy and fat diet, nasogastric tube or gastrostomy
normal energy Vitamin A,D,E,K supplementation
requirement )
Family history
Metabolic diseases HPT, DM
Hereditary diseases Consanguinity, Thalassemia, other siblings affected / screened as carrier
Social history
Smoke and alcohol Active and passive smoking, pack years – poorer prognosis
exposure Alcohol unit per week – increase risk of pancreatitis
Disease impact on patient Independence, normal social life, school performance, acceptance,
understanding and anticipation on disease, consideration of marriage, (for
male adolescent), infertility
Disease impact on family Financial constrain, discord in marriage, tension in parenting, neglect of
other children
Support Financial aid, insurance coverage, social supportive groups, information
source, counseling, training, main caretaker
Future plans Lung transplantation
B. Physical examination
Assess patients with CF for disease progression, severity and the current status of the disease. It looks
particularly at clubbing, flap, chest deformity, cor pulmonale, nutrition, puberty, diabetes, chronic liver
disease and hypertrophic pulmonary osteoarthropathy. Two very important signs are the cough and
the sputum.
General inspection Parameters Nutrition
- Weight, Height - Muscle bulk (protein); e.g. biceps,
- Head circumference quadriceps
- Percentiles - Subcutaneous fat, eg. mid-arm,
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Pubertal status (delay): breast, subscapular
pubic and axillary hair, voice, - Pallor (anaemia)
external genitalia
Peripheral stigmata of CLD,
Sick or well jaundice, anasarca
Vital signs Oedema (hypoproteineamia)
- Respiration
Use of oxygen supplement
- Pulse
Bedside adjuvants: inhaler
- Temperature
Sputum pot
- Urinalysis (glucose)
Upper limbs Nails Flap
- Clubbing - Hypercapnia
- Cyanosis - Liver failure (rare)
- Leukonychia (CLD)
Skin
Fingers - Bruising or petechiae (CLD,
- Fingertip prick marks (BSL testing) vitamin K deficiency)
- HPOA - Spider naevi (CLD)
- Scratch marks (cholestasis)
Palms
- Erythema (CLD) Muscle: bulk (palpate, if not done
- Crease pallor (anaemia) already)
Pulse
Axilla: hair, odour (Tanner staging)
- Paradoxus (severity of airway
obstruction)
- Alternans (CCF)
- Bounding (hypercapnia)
Head Eyes Mouth
- Conjunctival pallor - Angular cheilosis
- Scleral icterus - Central cyanosis (lips, tongue)
- Retinal venous dilation - State of teeth, dental hygiene
(hypercarbia) - Oral thrush
Ears Face
- Secretory otitis media - Cushingoid (systemic steriods)
- Hearing (aminoglycosides) - Acne and facial hair (pubertal
status)
Nose: Nasal polyps
Chest Inspection Palpation: Tracheal position, apex
- Chest deformity: pectus position, palpable P2
carinatum, increased AP diameter
(hyperinflation), thoracic Percussion for hyperinflation,
kyphosis consolidation
- Scars: previous pneumothorax,
bilateral lung transplant, venous Auscultation (note: may be normal
access port (eg.Port-A-Cath, even in moderately severe CF)
Hickman) - Air entry
- Tanner stage of breast - Breath sounds
development - Vocal resonance
- Harrison's sulcus - Adventitious sounds
- Chest expansion - Crackles
- Cough: moist, productive, request - Wheezes
sputum - Loudness of second heart sound

202
- Perform peak flow measurement if (pulmonary hypertension)
meter available (limited usefulness) - Gallop rhythm (cor pulmonale)
Abdomen Inspection Palpation
- Distension (poor abdominal - Liver ptosis (chest hyperinflation);
musculature with protein-calorie liver edge—is it firm, or is it bumpy
malnutrition, ascites with CLD) (cirrhotic)?
- Scars (e.g. gastrostomy, previous - Hepatomegaly (fatty liver with
meconium ileus, hepatobiliary malabsorption or corticosteroid
surgery for common bile duct use, CCF with cor pulmonale)
stenosis, fundoplication) - Splenomegaly (portal
- Venous access port (e.g. Infuse-A- hypertension)
Port) - Faecal masses (DIOS can present
- Prominent abdominal wall veins as a right iliac fossa mass)
(CLD) - Herniae
- Needle marks (diabetes mellitus) - Assess for ascites (fluid thrill,
- Tanner stage of pubic hair shifting dullness)
- Striae (corticosteroids)
- Examine genitalia
-Inspect anus for rectal prolapse
- Tanner staging
- Hydrocoele
Lower limbs Inspection Gait examination
- Toe clubbing - Peripheral neuropathy (vit E
- Bruising (vit K deficiency, CLD) deficiency)
- Joint swelling (arthropathy) - Cerebellar ataxia (vitamin E
deficiency)
Palpation: Ankle oedema
- Proximal muscle weakness
(hypoproteinaemia)
(corticosteroids)
C. Discussion
1. What is the differential diagnosis of recurrent lung infection?
- Bronchiectasis
- Congenital heart disease (paeds), heart failure causing pulmonary oedema / pleural effusion
acts as a breeding ground for bacteria
2. Why patient has to take nebulized saline and Ventolin?
- To clear respiratory secretions
- Ventolin acts as bronchodilator
3. What is the prognosis of cystic fibrosis?
- Median survival age is 36 years old
- 90% mortality due to respiratory disease, followed by liver cirrhosis
- Poorer prognosis if:
- Female sex (teenage and young adult age period);
- Pancreatic insufficiency;
- Complications, including CFRD or CFLD, or ABPA;
- Abnormal chest X-ray 12 months after diagnosis;
- Lung infection with B. cepacia;
- Age of acquisition of chronic pulmonary infection with P. aeruginosa under 6 years;
- Fall-off in growth curves
- Recurrent haemoptysis;
- Pneumothorax;
- Onset of cor pulmonale;
- Cigarette smoke exposure;
- Poor socio-economic status;
- Non-CF-clinic care.

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Bronchopulmonary Dysplasia (Chronic lung disease of prematurity)

Definition: *POG: Period of gestation


- Nelson: Infants with birthweight <1kg who were born at <28 week POG, have little/no lung
disease at birth but experience progressive respiratory failure over the first few weeks of life.
- Old: Oxygen requirement beyond 36 weeks post-menstrual age (PMA) or ≥28 postnatal days
(not account for extreme prematurity eg. birth weight <1kg or <30 weeks POG)
- NICHHD: Oxygen requirement for ≥28 postnatal days, classified as mild, moderate or severe
BPD depending on extent of oxygen supplementation.
(more accurately predicted pulmonary & neurodevelopmental outcomes at 18 to 22 months corrected age in
preterm infants <32 weeks GA with BPD than previous definitions, useful in NICU but lacking in predicting longer
term respiratory outcomes - From UpToDate)

Pathology:
- Chronic lung damage as a result of:
- Pressure & volume trauma (from artificial ventilation)
- Oxygen toxicity
- Infection (Pertussis, RSV)
- Accumulation of lung secretion
Clinical features:
- Chest hyperinflation, intercoastal & subcoastal recession
Chest X-ray of bronchopulmonary
- Crepitations on auscultation
disease showing hyperexpanded lungs
- Oxygen requirement (on any oxygen supply) with diffuse fibrosis. A nasogastric tube
Investigations: is in situ.

Imaging - CXR (persistent changes)


- Area of fibrosis (opacification) or lung collapse (atelectasis)
- `Honeycomb lung` (cystic pulmonary infiltrates in reticular pattern)
- Lung hyperventilation
- Area of emphysema & collapse
- Thickening of the pulmonary arterioles

Management:
Non- Pharmacological Pharmacological
- Artificial ventilation - Surfactant therapy
- Some may need long-term home O2 - Reduces duration of ventilation & reduces
- Others wean to cPAP, followed by BPD in ELBW group infants
additional ambient O2 - Corticosteroid (if ventilator dependent)
- Facilitate early weaning from ventilator
- Decrease O2 requirement
- May have long-term adverse effect on neuro-
developmental outcome (eg. CP),
hypertension, hyperglycaemia, hypertrophic
cardiomyopathy.
- Diuretics (if ventilator dependent)

Complications:
- Intercurrent infection
- Cor pulmonale or pulmonary hypertension
- Respiratory failure
- Air leaks, subglottic stenosis, tracheal stenosis (complication from ventilation)
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PART VI

GASTROENTEROLOGY
Acute Gastroenteritis (AGE)
Definition:
- Gastroenteritis is the inflammation of stomach & intestine
(hallmark: increased stool frequency with alteration in stool consistency)
- Acute gastroenteritis (<2 weeks duration)
- Chronic gastroenteritis (>2 weeks duration)
Epidemiology:
- Major cause of paediatric morbidity & mortality around the world, especially in developing
world. Dehydration is the most frequent & dangerous complication (ORS is life-saving)
- Related to malnutrition, poor hygiene, poor socioeconomic status, education level and bottle
feeding
Aetiology:
Virus Bacteria Parasite
- Rotavirus (most common) Enteroinvasive (Bloody diarrhoea) - Entamoeba histolytica
- Winter months epidermic - Campylobacter jejuni - Giardia lambdia
- Age btw 6 months & 2 years (commonest of bacterial origin) - Cryptosporidium spp
- Shigella - Cyclospora cayetanensis
- Salmonella
- Enteropathogenic E. coli (EPEC)
- Yersinia
Enterotoxigenic (Watery diarrhoea)
- Vibrio cholerae
- Enterotoxigenic E. coli (ETEC)
(commonly ask in OSCE station) - Bacillus cereus
- Adenovirus (40, 41) - Clostridium perfringens &
- Norovirus (Norwalk virus) difficile
- Coronavirus - Staph. aureus
- Astrovirus
- Pararotavirus
* Cholera & ETEC infection: profuse, rapidly dehydration diarrhea
* Campylobacter jejuni: severe abdominal pain
* Shigella & salmonella: dysentery, abdominal pain, tenesmus

Pathophysiology
- Acquired by person to person spread or ingestion of contaminated food and drink
- Colonisation of the gut by enteropathogens may or may not cause clinical symptoms
- When virulence of the organism > protective factor of the gut,
- Definitive clinical sequence of event is through invasive or enterotoxin route
- Mucosal injury & inflammation - interfering w fluid, electrolyte imbalance & gut absorption
Clinical feature:
- Diarrhoea (acute onset)
- Increased stool frequency, fluidity & volume compared to normal
- Stool weight >250g/day
- Greenish +/- mucus +/- blood or musty colour (invasive bacterial infection)
- Vomiting (acute onset)
- Abdominal pain and distention
- Fever, lethargy, dizzines (systemic manifestation)

205
Physical Examination:
- Assess hydration status (<5% dehydration there is no reliable clinical findings)
- Electrolyte imbalances:
- Acidosis: tachypnoea (Kussmaul breathing)
- Potassium depletion: hypotonia, weakness
- Hypocalcaemia: neuromuscular instability
- Hypoglycaemia: lethargy, coma, convulsions

Investigations:
Blood - FBC (leukocytosis)
- BUSE + creatinine (for dehydration & electrolyte imbalance)
- Hypo/hypernatremia, hypochloremia
- BUN: creatinine (disproportionate high in severe dehydration)
- Serum bicarbonate (low in metabolic acidosis)
- RBS (poor intake resuls in relative hypoglycaemia)
Stool - Stool for rotavirus antigen (eg. Rotaclone)
- Stool C&S (Salmonella, Shigella, Yersinia, Campylobacter)
- Stool red cells & leucocytes
- Stool ova & cyst
Others - ABG (metabolic acidosis)
- Urine osmolality (increased in dehydration)

Complications:
Renal - Oliguria (<200 ml/m2/day or <0.5 ml/kg/hr)
- If pre-renal AKI, urine osmolality>500, urine Na<10 mmol/L, urine urea
>250 mmol/L, urine:plasma osmolality ratio >1.3
- Urgent IV volume re-expansion, if no recovery of renal function, give
minimal maintenance fluid + losses only, without potassium, dialysis is
necessary if persistent hyperkalemia and uncorrected acidosis, recovery is
seen with polyuric phase of ATN
- Hypovolemic shock
- Electrolyte imbalance
- Metabolic acidosis
- Renal venous thrombosis (haematuria+renal mass)
- Haemolytic uraemic syndrome (haemorrhagic colitis by S.dysenteriae, E.coli
- Acute onset of miroangiopathic haemolytic anaemia, thrombocytopenia,
acute renal impairment, multisystem involvement)
CNS - Convulsions
- Hypernatraemia, hypoglycaemia, febrile convulsions, other electrolyte
disturbance, cerebral haemorrhage
- Usually associate with Shigella infection
GIT - Prolonged diarrhoea (>14 days)

Diagnosis:
- Clinical diagnosis, however AGE is diagnosis of exclusion (after excluding other differential
diagnosis as diarrhoea and vomiting are non-specific symptoms in young children)

206
Differential diagnosis:
Systemic infection - Septicemia
- Meningitis
Local infection - Respiratory infection
- Otitis media
- UTI
- Hepatitis A
Surgical cause - Pyloric stenosis
- Intussusception
- Acute appendicitis
- Necrotising enterocolitis
- Hirchsprung`s disease
Metabolic disorder - Diabetic ketoacidosis (DKA)
Renal disorder - Haemolytic uraemic syndrome (HUS)
Others - Coeliac disease
- Lactose intolerance
- Cow`s milk protein intolerance
- Adrenal insufficiency

Management:
- AGE wil lead to various degree of dehydration. According to APLS protocol, assessment of the
state of perfusion of child is the first step in management
- Identify whether child in shock (tachycardia, weak peripheral pulses, delayed capillary refill
time >2s, cold peripheries, depressed mental state with/without hypotension)
- If child is in shock, proceed to treatment Plan C immediately. Else, assess the degree of
dehydration using WHO chart as followed:

Assess
Look at general Well, alert Restless or irritable Lethargic or
condition of child unconscious
Look for eyes No sunken eyes Sunken eyes Sunken eyes
Offer child fluid Drinks normally Drinks eagerly, thristy Nor able to drink or
drink poorly
Pinch abdomen skin Skin goes back Skin goes back slowly Skin goes back very
immediately slowly (>2s)
Classify & Decide
Mild dehydration (<5%) Moderate dehydration Severe dehydration
IMCI: No signs of (5-10% dehydrated) (>10% dehydrated)
dehydration ≥2 above signs ≥2 above signs
IMCI: Some signs of
dehydration
Treat
Plan A Plan B Plan C
Give fluid and food to Give fluid and food for Give fluid for severe
treat diarrhoea at home some dehydration dehydration

Rehydration fluid:
Deficit = % dehydration x Weight (kg) + maintenance fluids + continuing losses
- Use 5% dextrose/0.45% saline (or 5% dextrose/0.9% saline) depending on plasma sodium & calculated
today body sodium. If severe acidosis (pH<7.0) treat with bicarbonate (half the deficit)
- Eg. 10 kg child with 5% dehydration has loss 5/100 x 10000 g = 500 ml of fluid deficit

207
208

Initial fluids for resuscitation of shock:
- 20 ml/kg of NaCl 0.9%
- Hartmann solution as a rapid IV bolus
- Repeated if necessary until patient is out of shock or if fluid
overload is suspected
- Review patient after each bolus
- Calculate the fluid needed over the next 24 hours:
- Fluid for Rehydration (also called fluid deficit) + Maintenance
(minus the fluids given for resuscitation)
- Fluid for Rehydration: percentage dehydration X body weight (g)
- Maintenance fluid (NaCl 0.45 / D5%)
- 1st 10 kg = 100 ml/kg
- 10-20 kg = 1000 ml/day + 50 ml/kg for each kg above 10 kg
- >20 kg = 1500 ml/day + 20 ml/kg for each kg above 20 kg

- Example:
A 6-kg child is clinically shocked and 10% dehydrated as a result of
gastroenteritis
- Initial therapy:
- 20 ml/kg for shock = 6 × 20 = 120 ml of 0.9% saline given as a
rapid IV bolus
- Estimated fluid therapy over next 24 hours:
- Fluid for Rehydration: 10/100 x 6000 = 600 ml
- 100ml/kg for daily maintenance fluid = 100 × 6 = 600 ml
- Rehydration + maintenance = 600 + 600 =1200 ml
- Start with infusion of 1200/24 = 50 ml/h
- The cornerstone of management is to reassess the hydration
status frequently (eg. at 1-2 hourly) and adjust the infusion as
necessary
- Start giving more of the maintenance fluid as oral feeds eg. ORS
(about 5 ml/kg/hour) as soon as the child can drink, usually after 3
to 4 hours for infants, and 1-2 hours for older children. This fluid
should be administered frequently in small volumes (cup and
spoon works very well for this process)
- Generally normal feeds should be administered in addition to the
rehydration fluid, particularly if the infant is breastfed
- Once a child is able to feed and not vomiting, oral rehydration
according to Plan A or B can be used and the IV drip reduced
gradually and taken off.

209
D) Indications for admission to Hospital:
- Moderate to severe dehydration
- Need for intravenous therapy (as below)
- Concern for other possible illness or uncertainty of diagnosis
- Substantial difficulties exist in giving ORS including intractable vomiting, ORS refusal or
inadequate ORS intake
- ORS treatment fails including worsening diarrhoea or dehydration despite adequate volume
- Patient factors (eg. young age, unusual irritability/drowsiness, worsening symptoms)
- Caregivers not able to provide adequate care at home
- Social or logistical concerns that may prevent return evaluation if necessary
* Lower threshold for children with obesity due to possibility of underestimating degree of dehydration.

E) Other indications for IV therapy:


- Unconscious child
- Continuing rapid stool loss (>15-20ml/kg/hour)
- Frequent, severe vomiting, drinking poorly
- Abdominal distension with paralytic ileus, usually caused by some antidiarrhoeal drugs (eg.
codeine, loperamide) and hypokalaemia
- Glucose malabsorption, indicated by marked increase in stool output and large amount of
glucose in the stool when ORS solution is given (uncommon)
* IV regime as for Plan C but the replacement fluid volume is calculated according to the degree of dehydration. (5%
for mild, 5-10% for moderate dehydration)

F) Other problems associated with diarrhoea:


- Fever
- May be due to another infection or dehydration
- Always search for the source of infection if there is fever, especially if it persists after the child is
rehydrated
- Seizures
- Consider:
- Febrile convulsion (assess for possible meningitis)
- Hypoglycaemia
- Hyper/hyponatraemia
- Lactose intolerance
- Usually in formula-fed babies less than 6 months old with infectious diarrhoea
- Clinical features:
- Persistent loose/watery stool
- Abdominal distension
- Increased flatus
- Perianal excoriation
- Diagnosis: compatible history; check stool for reducing sugar (sensitivity of the test can be greatly
increased by sending the liquid portion of the stool for analysis simply by inverting the diaper)
- Treatment: If diarrhoea is persistent and watery (over 7-10 days) and there is evidence of lactose
intolerance, a lactose free formula may be given
- Normal formula can usually be reintroduced after 2-3 weeks
- Cow`s Milk Protein Allergy
- Known potentially serious complication following acute gastroenteritis
- Suspected when trial of lactose free formula fails in patients with protracted course of diarrhoea
- Children suspected with this condition should be referred to a paediatric gastroenterologist for
further assessment
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G) Non-pharmacological / Nutritional strategies
- Undiluted vs diluted formula
- No dilution of formula is needed for children taking milk formula
- Soy based or cow milk-based lactose free formula
- Not recommended routinely. Indicated only in children with suspected lactose intolerance

H) Pharmacological agents
- Antimicrobials
- Should not be used routinely
They are reliably helpful only in children with bloody diarrhoea, probable shigellosis and
suspected cholera with severe dehydration
- Antidiarrhoeal medications
- The locally available diosmectite (Smecta®) has been shown to be safe and effective in
reducing stool output and duration of diarrhoea. It acts by restoring integrity of damaged
intestinal epithelium, also capable to bind to selected bacterial pathogens and rotavirus.
Other anti diarrhoeal agents like kaolin (silicates), loperamide (anti-motility) & diphenoxylate
(anti-motility) are not recommended
- Antiemetic medication
- Not recommended, potentially harmful
- Probiotics
- Probiotics has been shown to reduce duration of diarrhoea in several randomized controlled
trials. However, the effectiveness is very strain and dose specific. Therefore, only probiotic
strain or strains with proven efficacy in appropriate doses can be used as an adjunct to
standard therapy
- Zinc supplements
- It has been shown that zinc supplements during an episode of diarrhoea reduce the duration
and severity of the episode and lower the incidence of diarrhoea in the following 2-3
months. WHO recommends zinc supplements as soon as possible after diarrhoea has started.
Dose up to 6 months of age is 10 mg/day, age 6 months and above 20mg/day, for 10-14 days.

I) When ORS should not be given


- All children who are severely dehydrated, in state of shock or near shock require immediate
IV therapy
- Unconscious child
- Abdominal distension with paralytic ileus, usually caused by opiate drugs (eg. codeine,
loperamide) and hypokalaemia
- Glucose malabsorption (indicated by marked increase in stool output, faliure of the signs of
dehydration to improve & a large amount of glucose in stool when ORS solution is given
- Treatment:
- Rehydration should be given IV
- NG therapy should not be used

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Dehydration

Symptoms & Signs of Dehydration:


Blood - Decreased conscious level & responsiveness (irritable, lethargy)
- Sunken anteior fontanelle
- Sunken & tearless eye
- Dry mucous membrane (eg. mouth, lips)
Peripheries - Reduced skin turgor
- Prolonged capillary refill time
- Clod & clammy hands (peripheral vasoconstriction)
- Pale or mottled skin
Respiratory & CVS - Tachypnoea
- Tachycardia
- Hypotension
Others - Oliguria
- Sudden weight loss
* Bold indicating red flag signs: children at risk of progression to shock

Clinical Assessment of Dehydration:


No Clinical Dehydration Clinical Dehydration Shock
Body weight loss <5% 5-10% >10%
General appearance Appears well, thirst Appears unwell or Appears unwell or
deteriorating, thristy, deteriorating, drowsy,
restless or lethargy cold, sweating
Tears Present Reduced/absent Absent
Tissue elasticity Present Reduced/absent Absent
Skin colour Normal Normal Pale or mottled
Extremities Warm Warm Cold
Eyes Normal Sunken Grossly sunken
Anterior fontanelle Flat Sunken Very sunken
Mucous membrane Moist Dry Dry
Heart rate Normal Tachycardia Tachycardia
Breathing Normal Tachypnoea Tachypnoea
Peripheral pulses Normal Normal Weak
Capillary refill time Normal Normal Prolonged (>2s)
Skin turgor Normal Reduced Reduced
Blood pressure Normal Normal Hypotension (indicates
decompensated shock)
Urine output Normal Decreased Marked oliguria

Risks of dehydration in infants:


- Greater surface area to weight ratio then older children
- Greater insensible water losses (300 ml/m2/day or 15-17 ml/kg/day)
- Higher basal fluid requirement (100-120 ml/kg/day = 10-12% of body weight)
- Immature renal tubular reabsorption
- Unable to obtain fluids from themselves when thristy

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Principle of Management:
- If possible, use enteral (oral) route for fluids instead of intravenous fluid (IV)
- If IV fluid therapy is required, maintenance fluid reuirement should be calculated based on
weight (Holliday & Segar formula)
- Indications for prescribing IV fluid:
- Circulatory support in resuscitating vascular collapse
- Replacement of previous fluid & electrolyte deficit
- Maintenance of daily fluid requirement
- Replacement of ongoing losses
- Severe dehydration with failed NG tube fluid replacement (eg. ongoing profuse losses,
diarrhoea or abdominal pain)
- Certain co-morbidities, esp GIT (eg. short bowel or previous gut surgery)
A) Resuscitation
Crystalloids 0.9% NaCl
Ringer`s lactate @ Hartmann`s solution
Colloids Gelafundin, Voluven
4.5% albumin solution
Blood products Whoe blood, blood components
- Fluid deficit (can cause impaired tissue oxygenation eg. clinical shock, should be corrected with
fluid bolus of 10-20 ml.kg)
- Always reaccess circulation (give repeated boluses if necessary)
- Identify cause of circulatory collapse (blood loss, sepsis) for alternative resuscitation fluid
- Fluid bolus of 10ml/kg in selected condition (DKA, intracranial patholgy or trauma)
- Avoid hypotonic solution in resuscitation (risk of causing hyponatraemia)
- Blood glucose: treat hypoglycaemia with 2ml/kg of 10% Dextrose solution
- Measure Na, K, glucose at outset & at least each day from then on. More frequent in ill-patient
or those with co-morbidities. Rapid result can be done with blood gases measurement
- Consider septic work-up or surgical consult in severely unwell patients with abdominal
symptoms (eg. gastroenteritis)

B) Maintenance
- Volume of daily fluid intake, includes insensible losses (from breathing, perspiratoin, stool) &
allows excretion of daily production of excess solute load (urea, creatinine, electrolyte) in urine
- Most children can be safely managed with 0.45% NaCl with added glucose depending on
glucose requirement (0.45% NaCl in 5% glucose or 0.45% NaCl in 10% glucose)
- 0.18% NaCl with 5% glucose should NOT be used as maintenance fluid, restricted to specialist
to replace ongoing loses of hypotonic fluids (area of high dependency, renal, liver, ICU)
- In SIADH maintenance fluid requirement should restrict to 2/3 of normal recommendation
- Isotonic solution (eg. 0.9% NaCl +/- glucose) should be given for high risk of hyponatraemia
with careful monitoring to prevent iatrogenic hyponatraemia in hospital, these include:
- Peri-or post-operative
- Require replacement of ongoing losses
- Plasma Na at lower normal range (definitely if <135 mmol/L)
- Intravascular volume depletion
- Hypotension
- CNS infection, head injury, chronic disease (CF, DM, pituitary deficits)
- Bronchiolitis, sepsis, excessive gastric/diarrhoea losses, salt-wasting syndrome
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- Calculation of maintenance fluid:
Weight Total fluids Infusion rate
First 10 kg 100 ml/kg 4 ml/kg/hour
Subsequent 10 kg 50 ml/kg 2 ml/kg/hour
All additional kg 20 ml/kg 1 ml/kg/hour
Example: A child of 29 kg will require
- 100 ml/kg for first 10 kg 10 x 100 = 1000 ml
- 50 ml/kg for second 10 kg 10 x 50 = 500 ml
- 20 ml/kg for additional kg 9 x 20 = 180 ml
Total = 1680 ml (Infusion rate = 1680/24 = 70 mls/hour)

C) Deficit
- Replaced over a time period that varies according to child`s condition
- Rate of rehydration should be adjusted with ongoing clinical assessment
- Use an isotonic solution for replacement of deficit (eg. 0.9% NaCl)
- Reassess clinical status & weight at 4-6 hours, continue if satisfactory (If child lose weight,
increase fluid; if gain excessive weight, decrease fluid rate)
- Replacement is rapid in most cases of AGE (by oral or NG), but should be slower in DKA,
meningitis, much slower in hypernatraemic states (aim to rehydrate over 48-72 hours, serum
Na should not fall by >0.5 mmol/L/hr)
Example: 10 kg child who is 5 % dehydrated
Water deficit = 5% dehydration (5% of body water) x body weight (kg) x 1000 ml
= 500 mls (Infusion rate = 500mls/24 hours = 21mls/hour)

D) Ongoing losses
- Includes from drains, ileostomy, profuse diarrhoea
- Best measured & replaced (Any fluid losses >0.5 ml/kg/hr needs to be replaced)
- Calculation may base on each previous hour or each 4 hour period depending on situation
(eg. 200ml loss over previous 4 hours will replace with rate of 50ml/hr for next 4 hours)
- Can be replaced with 0.9% NaCl or Hartmann`s solution. Fluid loss with high protein content
leads to low serum albumin (eg. burns) can be replaced with 5% human albumin

Recommended Fluid Management of Dehydration:


No clinical dehydration Prevent dehydration
(mild dehydration) - Continue breast-feeding or other milk feeds
<5% body weight loss - Encourage fluid intake to compensate for ↑ GI losses
- Discourage fruit juces & carbonated drinks
- ORS as supplemental fluid if ↑ dehydration (40-60 ml/kg within 4-6 hours)
- For every diarrhoea episode, replace with ORS 10 ml/kg
Clinical dehydration Oral Rehydration Solution (ORS)
(moderate dehydration) - Fluid deficit replacement (40-60 ml/kg within 4-6 hours)
5-10% body weight loss - If Na>150 mmol/L, gives replacement for 12-16 hours
- Maintenance fluid is required
- Give ORS often, in small amounts
- Continue breastfeeding, consider supplemental ORS with usual fluids
- Conisder NG tube if inadequate fluid intake or persistent vomiting
Shock Intravenous therapy (IV)
(severe dehydration) - Give rapid infusion of 0.9% NaCl solution, repeat if necessary
>10% body weight loss - If remains shocked, consult paediatric ICU specialist
214
- Replace fluid deficit & give maintenance fluids
- Fluid deficit (% dehydration x weight in kg)
- 100 ml/kg (10% body weight) if initially shocked
- 50 ml/kg (5% body weight) if not shocked
- Can be replaced over 12-24 hours together with maintenance
requirement using 0.45% NaCl/5% dextrose
- Duration should be prolonged (48-72 hours) if hypernatraemia
- For maintenance fluid, refer formula below
- Give 0.9% NaCl or 0.9% NaCl + 5% glucose
- Monitor plasma eletrolytes, urea, creatinine, glucose, consider IV K+
- Continue breastfeeding if possible
- Ongoing losses must be replaced for any fluid losses >0.5ml/kg/hr
- Add 10 mmol KCL to each 500 ml of IV fluid after urine is passed

Management of electolyte Imbalance:


A) Sodium balance in dehydration:
- Daily [Na] requirement is 2-3 mmol/kg/day
- Normal [Na] is between 135-145 mmol/L
- Hypernatraemia defined as [Na] >150 mmol/L (moderate: 150-160 mmol/L; severe >160 mmol/L)
- Hyponatraemia defined as [Na] <135 mmol/L
Isonatraemic & Hyponatraemic Hypernatraemic
- Total body deficit of sodium and water - Water loss exceeds relative sodi
- Proportional loss of sodium and water, plasma - Plasma sodium concentration increases
sodium within normal range (isonatraemic) (hypernatraemic)
- Consume large amount of water or hypotonic - Results from
solution, greater net loss of sodium than water, - High insensible water losses (high fever, hot dry
fall in plasma sodium (hyponatraemic) environment)
- Shift of water from ECF to ICF (increase brain - Water deficit (diabetes insipidus)
volume) → convulsions (hyponatraemic - Profuse, low-sodium diarrhoea
encephalopathy is a medical emergency!) - Sodium gain (salt poisoning, NaHCO3 infusion)
- ECF volume depletion → greater degree of shock - ECF (hypertonic) → Fluid shift from ICF to ECF
per unit of water loss - Signs of ECF depletion less obvious (depressed
- More common in poorly nourished infants in fontanelle, reduced tissue elasticity, sunken eyes)
developing countries - Dangerous (cerebral shrinkage→jittery
movement, hypertonia, hyperreflexia, altered
consciousness, seizures & multiple, small cerebral
haemorrhages, ataxia, tremor, `doughy` skin)
- Transient hyperglycaemia (self-correcting)
Management (for hyponatraemia): Management:
- Bolus of 4ml/kg of 3% NaCl administered over 30 - Depending on the cause of hypernatraemia
minutes to raise sodium by 3 mmol/L (helps to - If in shock, give resuscitation volume with 0.9%
stop hyponatraemic seizures) normal saline as required with bolus
- Gradual [Na] correction should not >8mmol/day - Avoid rapid correction (may cause cerebral
to prevent osmotic demyelination syndrome oedema, convulsion & death)
- Calculation of sodium correction is necessary - Aim for deficit correction over 48-72 hours & [Na]
- In asymptomatic hyponatraemia, 3% NaCl not fall not >0.5 mmol/L/hr.
require if oral fluids/IV rehydration with 0.9% - Maintenance volume is given as well to replace
NaCl is possible ongoing losses following resuscitation volume
- In hyponatraemia with normal/raised volume, - Repeat BUSE every 6 hours until stable
fluid restriction is necessary - Slower rate if chronic hypernatraemia (>5 days)
- Aware of hyponatraemia secondary to DKA - Aware of hypocalcaemia & hyperglycaemia
215
Corrected Na required (mmol) = (135 - present Na) x 0.6 x weight (kg) .
- Calculated requirements can then be given from following available solutions dependent on availability
& hydration status: 0.9% NaCl (154 mmol/L), 3% NaCl (513 mmol/L)

B) Potassium disorders
- Daily potassium requirement: 1-2 mmol/kg/day
- Normal [K]:
- At birth - 2 weeks : 3.7-6.0 mmol/L
- 2 weeks - 3 months : 3.7-5.7 mmol/L
- Beyond 3 months : 3.5-5.0 mmol/L
Hyperkalaemia Hypokalaemia
- Serum [K] > 5.5 mmol/L - Serum [K] < 3.0 mmol/L or [Na] > 3.4 mmol/L
Causes: Causes:
- Dehydration - Sepsis
- Acute renal failure - GI losses (eg. diarrhoea, vomiting)
- Diabetic ketoacidosis - Iatrogenic
- Adrenal insufficiency (eg. diuretic therapy, salbutamol, amphotericin B)
- Tumour lysis syndrome - DKA
- Drugs - Renal tubular acidosis
(eg. oral K supplement, K-sparing diuretics, ACEi) - Hypomagnesaemia (refractory hypoK)
ECG changes: ECG changes: (when K+<2.5 mmol/L)
- Tall, tented T waves - Prominent U wave
- Prolonged PR interval - ST depression
- Prolonged QRS complex - Flat, low or diphasic T waves
- Loss of P wave, wide biphasic QRS - Prolonged PR interval (severe hypoK)
- Sinoatrial block (severe hypoK)
Management: Management:
- Stop all K+ supplementation - Identify and treat underlying condition
- Stop medication causing hyperkalaemia - Unless symptomatic, K+ of 3.0-3.4 mmol/L is
- Cardiac monitoring generally not supplemented but rather
- Exclude pseudo-hyperkalaemia (recheck venous) monitored in the first instance
- If child unstable, symptomatic, abnormal ECG, - Oral supplementation
K>7mmol/L - Oral KCl (max of 2 mmol/kg/day in divided dose
- Discuss for dialysis is common but more may be required in
- IV calcium practice)
- Nebuliser Salbutamol - IV supplementation (1g KCl = 13.3 mmol KCl)
- IV insulin with glucose - KCl is always given by IV infusion, NEVER by
- IV bicarbonate bolus injection
- +/- PR/PO Resonium (K+ binder) - Max concentration via peripheral vein is 40
- If child stable, normal ECG, K+>6, ≤7 mmol/L: mmol/L (concentration up to 60 mmol/L can be
- Nebuliser salbutamol used after discussion with senior medical staff)
- IV insulin with glucose - Max infusion rate of 0.2 mmol/kg/hr (in non-ICU
- +/- IV bicarbonate if acidosis setting)
- +/- PR/RO Resonium - IV correction (1g KCl = 13.3 mmol KCl)
- If child stable, asymptomatic, normal ECG, - K+<2.5 mmol/L may be associated with
5.5 ≤ K+≤ 6 mmol/L significant CVD compromise, in emergency, IV
- Consider treatment if necessary KCl infusion may be given:
- +/- Nebuliser Salbutamol - Dose: Initially 0.4 mmol/kg/hr into central vein
- +/- IV bicarbonate if acidosis till K+ level is restored
- +/- PR/RO Resonium - Ideally this should occur in ICU setting

216
Gastroesophageal Reflux Disease (GERD)
Introduction:
- Gastro-oesophageal reflux (GER)
- Involuntary passage of gastric contents into oesophagus with/without regurgitation and vomiting
- Normal physiological process occurring several times per day in healthy children
- Generally associated with transient relaxations of the lower oesophageal sphincter independent of
swallowing, which permits gastric contents to enter the oesophagus.
- Gastro-oesophageal reflux disease (GERD) is present when
- Reflux of gastric contents causing troublesome symptoms or complications due to frequent or
persistent GER, producing esophagitis-related symptoms or extraesophageal presentations (eg.
respiratory symptoms or nutritional effects)

Epidemiology:
- Common in the first year of life due to: (mostly resolve spontaneously by 1 year of age)
- Maturation of lower esophageal sphincter
- Upright posture
- Introduction of more solid diet
Anti-reflux Mechanism:
- Presence of LES, below the diaphragm (increased intra-abdominal pressure reinforce LES tone)
- Oblique entry of esophagus to the stomach
- Secondary peristaltic wave in oesophagus clears the refluxed material
- Swallowed saliva neutralises the refluxed acid
Pathophysiology:
Infants Older Children/ Adults
- Functional immaturity of LES - Reduced esophageal clearance of acid due to
- Episodes of inappropriate relaxation poor esophageal peristalsis
- Short intra-abdominal esophageal length - Exacerbated by sliding hiatus hernia (Trapping
- Predominantly fluid diet of acid within hernial sac)
- Horizontal posture - Reduced esophageal mucosal resistance
- Delayed gastric emptying
- Inflammation of LES by exposure to acid, pepsin & bile
Clinical features:
Infants Older Children/ Adults
- Frequent vomiting & regurgitation* - Heartburn (retrosternal chest pain)
- Crying, poor sleeping, irritability - Aggravated by stooping, bending & lying down
- Feeding refusal, poor weight gain, sour burps - Vomiting, regurgitation, dysphagia
- Extra-oesophageal symptoms (aspiration - Acid & water brash
pneumonia, URTI, choking, coughing, wheezing) - Odynophagia, hoarseness of voice
* Regurgitation is an involuntary retrograde - Symptoms of anaemia (due to blood loss)
propulsion of stomach content via gastroesophageal - Extra-oesophageal (recurrent pneumonia,
junction to the mouth. chronic sinusitis, laryngitis, dental erosions)
Risk factors:
- Sliding hiatus hernia - Thoracic stomach
- Cerebral palsy - Coeliac disease
- Bronchopulmonary dysplasia (in preterm) - Raised ICP
- Post-surgery (oesophageal atresia, - UTI
diaphragmatic hernia) - Congenital heart disease
- Cystic fibrosis - Fictitious or induced illness
217
Warning signals: (requiring investigations in fants with recurrent regurgitation or vomiting)
Symptoms of GI obstruction Systemic/neurologic disease Non-specific symptoms
- Bilous vomiting - Hepatosplenomegaly - Fever
- GI bleeding (haematemesis, - Bulging fontanelle - Lethargy
haematochezia) - Macro/microcephaly - Failure to thrive (FTT)
- Consistent forceful vomiting - Seizures
- Onset of vomiting after 6 - Genetic disorders
months of life (eg. Trisomy 21)
- Constipation - Other chronic disorders
- Diarrhoea (eg. HIV)
- Abdominal tenderness,
distension

Complications:
General - Failure to thrive
- Feeding problems
- Apnea in preterm infants
- Faltering growth
- ALTE (Apparent life threatening event)* contraversial
SIDS (Sudden infant feath syndrome)
Head - Sandifer`s syndrome
(dystonic movement of head and neck, spasmodic torticollis)
Oesophagus & stomach - Oesophagitis (dysphagia, odynophagia, hematemesis, pain)
- Peptic stricture (associate with oesophagitis)
Respiratory system - Aspiration pneumonia
Social - Smelly mouth due to regurgitation

Investigations:
24 hour pH measurement - Monitor pH for 24 hours
(Gold standard) (Normal ≤ 4%, abnormal > 4%)
Endoscopy with biopsy - Look for oesophagitis, peptic stricture, Barrett`s esophagus,
enteropathy in older children, gastritis or PUD
Barium swallow and meal - Look for underlying anatomical abnormalities of oesophagus,
stomach or duodenum (eg. hiatus hernia, malrotation, oesophageal
stricture)
Others - CXR, urine, C&S, Hb and iron studies, faecal occult blood.
* Raised ICP may cause reflux as well

Management:
Conservative Operative
Feeding modification - Nissen fundoplication (fundus of stomach is
- Small volume, frequent feeds wrapped around the intra-abdominal
- Head prop up to 30o after feeding oesophagus)
- Thickening of feeds (Nestargel, Carobel, carob
seed flour) - Reserved for patient who:
- Fail to respond to medication
Pharmacological - With esophageal stricture
- Antacid (Ranitidine & Omeprazole) - With recurrent aspiration pneumonia
- Alginate & Antacid combination (Gaviscon)
- Motility stimulator (Metoclopramide)
- Prokinetic agents (Cisapride)
218
Inflammatory Bowel Disease
Definition:
- Chronic, idiopathic, immune-mediated, inflammatory disease involving the gastrointestinal
(GI) tract
- Two subtypes: Crohns Disease (CD) & Ulcerative Colitis (UC)

Epidemiology:
- In the pediatric population, Crohn`s disease is more common than UC, with the majority of
children diagnosed in adolescence, although some are much younger
- Prevalence is about 9/100,000 population. Thus, it is estimated that there are about 2000
existing cases in Malaysia
- Worldwide distribution, ↑incidence of IBD in developed countries than developing countries
- Most common onset of IBD is during preadolescent/adolescent & young adulthood
- Bimodal distribution of age: early onset at 10-20 years, smaller peak at 50-80 years of age
- Approximately 25% of patients present <20 years of age, may begin as early as 1st year of life
- Children with very early onset (<6 yr) & <1 yr have ↑incidence of monogenetic cause of IBD
- Monozygotic twins affected more than dizygotic twins in development of IBD (CD > UC)
- Associated genetic disorders: Turner syndrome, Hermansky-Pudlak syndrome, glycogen
storage disease type 1b & immunodeficiency diseases
Pathology:
- Ulcerative colitis (UC) is characterized by diffuse colonic mucosal inflammation that begins at
anal verge and extends proximally. It is limited to the colon, although distal ileal involvement
(backwash ileitis) may occur
- Crohns disease is characterized by transmural inflammation that may involve any segment of
intestinal tract from the mouth to the anus
Aetiology:
- Multifactorial with probable contributions from genetics and the environment
- There is a high incidence of disease among first- degree relatives.
- Defective IBD1 gene cause reduced immune tolerance to luminal bacteria, a process mediated
by proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1),
IL-6, interferon-γ, and IL-23

219
Clinical Features:
Symptoms Signs
Intestinal Manisfestation: General:
- Per rectal bleeding (mucus, pus-filled, UC>CD) - Right/ Left lower quadrant abdominal pain
- Diarrhoea (nocturnal, differentiate from irritable - Generalized abdominal fullness
bowel syndrome) - Oral Ulcer
- Abdominal pain - Clubbing
- Tenesmus, urgency - Pyrexia
- Steatorrhoea - Severe anaemia (fulminant colitis, >5 bloody
- Constipation (less common,in those with stools/day for 5 days in UC or due to poor intake)
proctitis) - Failure to Thrive (underplotted in Growth Chart)
Systemic: Extraintestinal: (more common in UC than CD)
- Fever - Erythema nodosum (red, raised, tender nodules
- Weight Loss located along the anterior shins)
- Anorexia, malaise, easy fatigability - Pyoderma gangrenosum (deep necrotic ulcers
- Growth failure (inadequate calorie, suboptimal often on the legs)
absorption/excessive nutrient loss, LOA, use of - Jaundice (sclerosing cholangitis, chronic active
steriods during treatment) hepatitis)
- Episcleritis, uveitis, and iritis
Extraintestinal Manisfestation:
- Liver tenderness
- Arthralgia
- Secondary amenorrhoea (active disease)
- Arthritis (non-deforming)
- Pubertal delay (Tanner staging)
- Skin rashes
- Perianal disease (tag, fistula, fissure, abcess)
- Eye involvement
- Pneumaturia, faecaluria (enterovesical vaginal)

Complications:
1) Intestinal:
- Stricturing & adhesion (luminal narrowing, pre-stenotic dilation, intestinal obstruction)
- Perianal/perirectal fistulae → abscesses, sinus tract (incomplete fistula ending in a `cul-de-sac`)
- Severe hemorrhage, toxic megacolon or perforation
- Long-term: colonic malignancy
2) Extra-intestinal:
Musculoskeletal - Peripheral arthritis, granulomatous monoarthritis, synovitis, periosteitis
- Sacroiliitis, ankylosing spondylitis, RA (HLA-B27 association)
- Finger clubbing, Hypertrophic osteoarthropathy
- Osteoporosis, osteomalacia (due to malabsorption, malnutrition,
inadequate calcium and vitamin D intake, chronic steroid use, inactivity,
and chronic inflammation)
- Rhabdomyolysis, pelvic osteomyelitis, recurrent multifocal osteomyelitis
Skin & mucous - Oral lesions, cheilitis, aphthous stomatitis, glossitis
membrane - Granulomatous oral Crohn disease, peristomatitis vegetans
- Inflammatory hyperplasia fissures & cobblestone mucosa (CD)
Dermatologic - Erythema nodosum, Pyoderma gangrenosum, Polyarteritis nodosa
- Sweet syndrome, Metastatic Crohn disease
- Perianal skin tags
- Epidermolysis bullosa acquisita
Ocular - Conjunctivitis, uveitis, iritis, episcleritis, scleritis
- Retrobulbar neuritis, Chorioretinitis with retinal detachment
- Crohn`s keratopathy, retinal vascular disease
Bronchopulmonary - Chronic bronchitis with bronchiectasis/ neutrophilic infiltrate
220
- Fibrosing alveolitis, Pulmonary vasculitis, bronchiolitis obliterans
- Eosinophilic/granulomatous lung disease, Tracheal obstruction
Cardiac - Pleuropericarditis
- Cardiomyopathy, endocarditis, myocarditis
Malnutrition - ↓ food intake (IBD, dietary restriction)
- Malabsorption (IBD, bowel resection, bile salt depletion, bacterial
overgrowth)
- Intestinal losses (electrolytes, minerals, nutrients)
- ↑ caloric needs (inflammation, fever)
Haematologic - Anaemia (iron-deficiency-blood loss, chronic disease, VitB12 deficiency)
- Anaphylactoid purpura (CD)
- Hyposplenism
- ↑ risk of arterial & venous thrombosis with stroke, MI, PVD
- AIHA, ↑ activation of coagulation factors, activated fibrinolysis
Renal & genitourinary - Urinary crystal formation (nephrolithiasis, uric acid, oxylate)
- Hypokalemic nephropathy, Renal amyloidosis
- Inflammation (retroperitoneal/perianal/psoas abscess, ureteral fibrosis)
- Fistulation (enteroenteric, enterocolonic, enterovesical, enterovaginal,
enterocutaneous)
- Glomerulitis, membrane nephritis, nephrotic syndrome
Hepatobiliary - Pancreatitis secondary to medications (sulfasalazine, 6-MCP,
azathioprine, parenteral nutrition)
- Granulomatous pancreatitis, sclerosing cholangitis with pancreatitis
- Primary sclerosing cholangitis, cholelithiasis, autoimmune hepatitis,
cholecystitis (immune-mediated)
- Hepatic abscess, hepatic granuloma
- Pericholangitis, carcinoma of bile ducts, NASH
Endocrine - Growth failure (more in CD), delayed sexual maturation
- Thyroiditis
Neurological - Peripheral neuropathy, meningitis, vestibular dysfunction
- Pseudotumour cerebri
- Cerebral vasculitis, migraine

Investigations:
Baseline - FBC (anemia, thrombocytosis, leukocytosis: toxic megacolon)
- ↑ESR, ↑CRP
- Hypoalbuminaemia (↓nutritional status)
- ↑AST/ALT (autoimmune hepatitis), ↑GGT,↑ALP,↑TSB (primary sclerosing
cholangitis, cholelithiasis)
Diagnostic Antibody screening, need to check for both:
(need to couple the - Anti-neutrophil cytoplasmic antibody (p-ANCA)
findings with history, PE - Anti-Saccharomyces cerevisiae antibody (ASCA)
and HPE from biopsy) p-ANCA +ve, ASCA -ve suggestive of UC
p-ANCA - ve, ASCA +ve suggestive of CD
Upper endoscopy + colonoscopy or wireless capsule endoscopy
- Erythema, aphthous ulcers, cobblestone appearance, pseudopolyps,
and mucosal friability in Crohn`s Disease
- Signs of inflammation starting in the rectum, extending proximally in a
continuous fashion, longitudinal ulcers in Ulcerative Colitis
Mucosal biopsy
- Inflammatory infiltrates with crypt distortion and crypt abscesses
consistent with chronic active inflammation are diagnostic for IBD.
221
Others - Stool studies for bacteria, parasites & viruses (infectious diarrhoea)
- CT scan used in emergency (acute abdomen, ischaemic colitis, mesenteric
ischaemia)
- Faecal calprotectin (↑ indicates GI inflammation, specific marker)

Classifications:

Ulcerative colitis
1) Monstreal classification based on extent (E) & severity (S)
E1 (proctitis) Inflammation limited to rectum
E2 (left-sided, distal) Inflammation limited to splenic flexure
E3 (pancolitis) Inflammation extends to proximal splenic flexure
S0 (remission) No symptoms
S1 (mild) ≥ 4 stools/day (with/without blood), absence of systemic
symptoms, normal inflammatory markers
S2 (moderate) 4 stools/day, minumum signs of systemic symptoms
S3 (severe) ≥ 6 bloody stools/day, PR ≥ 90bpm, temp ≥ 37.5`C, Hb <10.5g/dL,
ESR ≥ 30 mm/hour

2) Mayo endoscopic score

(A) Score 0 = normal; endoscopic remission


(B) Score 1 = mild; erythema, decreased vascular pattern, mild friability
(C) Score 2 = moderate; marked erythema, absent vascular pattern, friability, erosions
(D) Score 3 = severe; spontaneous bleeding, ulceration

Crohn`s disease
1) Montreal classification based on age (A), location (L) & behaviour (B)
Age at Diagnosis A1: Less than 16 years old
A2: Between 17-40 years old
A3: Over 40 years old
Location L1: Ileal
L2: Colonic
L3: Ileocolonic
L4: Isolated upper GI
Behaviour B1: Non-stricturing, non-penetrating
B2: Stricturing
B3: Penetrating
P: Perianal disease

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2) Lémann score

- New technique to
score & study
intestinal damage in
Crohn disease
- Disease phenotypes
often change as
duration of disease
lengthens
(inflammatory
becomes structuring/
penetrating)

Difference between Crohn`s disease & Ulcerative colitis:


Features Crohn`s Disease Ulcerative Colitis
Rectal bleeding Sometimes Common
Diarrhoea, mucus, pus Variable Common
Abdominal pain More to right-sided More to left-sided
Abdominal mass Common Not present
Growth failure Common Variable
Perianal disease Common Rare
Rectal involvement Occasional Universal
Pyoderma gangrenosum Rare Present
Erythema nodosum Common Less common
Mouth ulceration Common Rare
Thrombosis Less common Present
Colonic disease 50-75% 100%
Ileal disease Common None except backwash ileitis
Stomach-esophageal disease More common Chronic gastritis can be seen
Strictures Common Rare
Fissures Common Rare
Fistula Common Rare
Toxic megacolon None Present
Sclerosing cholangitis Less common Present
Risk for malignancy ↑ ↑↑
Discontinuous (skip) lesion Common Not present
Cobblestone appearance Present Absent
Transmural involvement Common Only mucosa/submucosa
Crypt abscesses Less common Common
Ulceration Serpentine Longitudinal
Granulomas Common None
Linear ulceration Uncommon Common
p-ANCA +ve <20% 70%
Anti-Saccharomyces cerevisiae Ab +ve 55% 25%

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Differential diagnosis:
- Irritable bowel syndrome
- Infectious colitis
- Bacteria (Campylobacter jejuni, Yersinia enterocolitica, C. diffile, E. coli O157:H7, Shigella)
- Parasites (Entamoeba histolytica, Giardia lamblia)
- AIDS-associated enteropathy (Cryptosporidium, Isospora belli, CMV)
- Lactose intolerance
- Coeliac disease
- Drug-induced colitis (NSAIDS)
- Hyperthyroidism
- Neuroendocrine tumor
Management:
Medical - Aminosalicylates, including sulfasalazine and mesalamine (inhibiting the
cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism,
which alters mucosal prostaglandin production). Given orally or rectal suppository.
- Systemic corticosteroids such as oral prednisone. Corticosteroid dependence,
defined as recurrent symptoms when the dose is gradually tapered, is a common
occurrence and may require an increased dose or additional therapy with
immunomodulators.
- Budesonide is a synthetic steroid, fewer side effects and less adrenal suppression
than prednisone. For short term therapy.
- Antibiotic therapy, eg. metronidazole and ciprofloxacin for complications of
Crohns disease, such as C. difficile infection and perianal fistulae.
- Immunomodulators eg. methotrexate, 6-mercaptopurine (6-MP) and
azathioprine for active disease (S/E: leucopenia, thrombocytopenia, hepatitis,
infection, pancreatitis, and allergic reaction)
- Infliximab is a humanized anti-TNF-α antibody used to treat severe and fistulizing
IBD (first-line therapy in conjunction with corticosteroids)
Surgical - Indications for surgery:
- Failed medical intervention
- Symptomatic patients
- Bowel stricture or obstruction
- Uncontrollable GI bleeding
- Intraabdominal abscess, perianal abscess, and fistula
- Types of surgery:
- Small bowel resection (as limited as possible to prevent short bowel syndrome)
- Colectomy (intractable disease, complication of therapy, fulminant colitis)
- Abscess drainage
- Seton placement for perianal abscess (not completely remission)
Nutritional - In children with growth failure, exclusive enteral nutrition therapy with special
therapy formulas is prescribed.
- Formulas are best tolerated by nasogastric tube because most formulas are not
very palatable.
Psychosocial - Family support, social workers, individual psychologic counseling
support - Ensure parent understand disease manifestations & management
- Encourage patient to participate fully in age-appropiate activites (↓ during periods
of exacerbation)
Surveillance - Begin after 8-10 years of disease to detect dysplastic changes from biopsy
colonoscopy - Immediate colectomy is needed if suggest of progression to colon cancer (esp UC)

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Prognosis:
- There is no cure for IBD
- Goal of therapy is maintenance of long-term remission, normal growth & nutritional status
- Once a child has had UC for 8-10 years, general risk of colon cancer is 1% per year, and by 20
years may be up to 25%
- If a child has continuous disease, or a frequently relapsing course, risk of malignancy is greater
than in those with less severe disease
- In IBD patients, there is an overall increased risk of lymphoma in those exposed to biological or
immunomodulator therapy
Inflammatory Bowel Disease Long Case (Template)
A. History
General profile (Age, Gender, Ethnicity)
History taken from caretaker/parent
Presenting complaints
(Reason for admission)
HOPI - Present according to current condition, remember to rule out other differential diagnosis. If
presenting complaint is related to IBD, focus on IBD under HOPI not under past-medical section
Gastrointestinal symptoms Weight loss, growth, abdominal pain (site, interference with sleep,
precipitation by eating), anorexia, nausea, vomiting, odynophagia or
dysphagia , diarrhoea, urgency, tenesmus, incontinence, rectal bleeding,
fistulae perirectal disease (CD)
Extraintestinal symptoms - General (rashes eg. erythema nodosum: CD, fever, pubertal delay)
(systemic) - Mouth involvement (aphthous ulcers)
- Liver involvement (chronic active hepatitis)
- Joint disease (arthralgias, spondylo-arthropathies)
- Visual problems (uveitis), vascular complications (vasculitis)
- Renal tract involvement (nephrolithiasis)
- CVS (hypertension, myocarditis, pericarditis)
- Neurological problems (peripheral neuropathy)
- Haematological disease (anaemia)
- Musculoskeletal weakness (vasculitic myositis, steroid-induced
myopathy)
- Hepatobiliary (jaundice, pancreatitis)
- Extraintestinal neoplasia (lymphoma)
- Others (amyloidosis, thromboembolic disease - cerebral, retinal)
Progression of Disease
1. Initial presentation, symptoms, when, where and how diagnosed, response to treatment
2. Details of subsequent hospitalisations (frequency, indications, usual length of stay, usual outcome,
doctors involved, clinics attended, previous hospitalisations, past surgery)
3. Complications of the disease
4. Complications of treatment
5. Monitoring of the disease: how often seen in clinic, usual investigations performed, how often seen
by local doctor
Past-Medical & Surgical History
Past-Medical - Other than associated conditions of IBD
Past-Surgical - Any other operation done
Drug History
Drugs - Current medication, change in medication, compliance, control
- Drug allergy
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Family History
Parent & siblings - Inflammatory bowel disease, ankylosing spondylitis, rheumatoid arthritis
Paediatrics History
Birth history - Neonatal anaemia? IUGR? G6PD deficiency?
Immunisation history - Completed immunisation?
Developmental history - Any developmental delay?
- Delayed pubertal staging
Dietary - Any enteral/parenteral nutrition needed
- Food allergy
Social History
Disease impact on the - Schooling (which stream, level), Academic performance (rank, best
child subject), able to take part in physical class/sports?
- Problems of chronic disease: energy levels, behavioural problems,
chronic hospitalisation, altered self-image, school absence, depression,
feeling of missing out due to disease exacerbations and energy levels
- Psychosocial (depression, low self-esteem & relationship)
- Cigarette smoking (exacerbates CD)
- Steroid effects, short stature, delayed sexual development
- Body image, pubertal anxieties (in teens)
Disease impact on the - Occupation of caretakers
family - Financial considerations (financial burden of multiple hospitalisations,
surgical procedures)
- Social support group available
- Social worker, parent support groups, psychologist, online `chat groups`
for teenagers
Understanding of disease - Perception of disease
- Compliance with medications
Summary
- Summarise patient (name,age,gender) with presenting complaint & underlying IBD
- Provisional diagnosis and differential diagnosis
- Current functional status & Complications from IBD
B. Physical Examination
General inspection:
- Parameters (weight, height, percentiles, growth chart)
- Tanner staging
- Nutritional status (muscle bulk, subcutaneous fat, peripheral oedema)
- Pallor
- Jaundice
- Cushingoid appearance
- Abdominal scars and stoma
- Joint swelling (especially lower limbs)
- Skin rashes (erythema multiforme, erythema nodosum, pyoderma gangrenosum)
Upper limbs:
- Clubbing (especially CD)
- Palmar crease/nailbed pallor (anaemia from dietary deficiency, iron loss in gut, folate malabsorption,
vitamin B12 malabsorption, chronic disease, or side effects of salazopyrine)
- Arthritis (wrists, elbows)
- Palpable epiphyseal enlargement (vitamin D deficiency)
Head & Neck:
- Cushingoid facies

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- Conjunctival pallor (anaemia)
- Conjunctivitis scleral icterus (sclerosing cholangitis, chronic active hepatitis)
- Iritis
- Corneal xerosis or clouding (vitamin A deficiency)
- Cataracts (if on steroids)
- Aphthous stomatitis
Abdomen:
- Scars
- Stoma
- Striae (if on steroids)
- Tenderness Mass (matted loops or abscess)
- Hepatomegaly (sclerosing cholangitis, chronic active hepatitis)
- Ascites (protein deficiency, protein- losing enteropathy in CD)
- Enlarged kidneys (hydronephrosis in CD from ureteral compression by inflammatory mass or fibrosis)
- Fistulae (CD)
- Gluteal wasting
- Perianal disease (anal fissures, fistulae, abscesses, anal tags)
- Rectal examination (blood, pus on glove)
Lower limbs:
- Joint swelling (knees, ankles)
- Tibial bowing (vitamin D deficiency)
- Erythema nodosum, pyoderma gangrenosum
- Toe clubbing
C. Discussion
- Refer previous pages for detailed investigation and management in IBD.
- Mainstay of management can be catogorised into medical, surgical, nutritional & psychosocial
intervention. Discuss on the complications which would be faced by patient in future and necessary
management as a whole.

UC. Double-contrast barium enema in a 5 yr old boy who had


had intermittent intestinal and extraintestinal symptoms since
the age of 3 yr.
(A) Small ulcerations are distributed uniformly about the
colonic circumference and continuously from the rectum to
the proximal transverse colon. This pattern of involvement is
typical of ulcerative colitis.
(B) In this coned view of the sigmoid in the same patient, small
ulcerations are represented by fine spiculation of the colonic
contour in tangent and by fine stippling of the colon surface
en face

Stenosis in Crohn disease.


(A) MR enterography of Crohn disease restricted
to the terminal ileum (Montreal category L1) with
inflammatory stenosis.
(B) Ultrasound image of an intestinal stenosis in
Crohn disease.

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Hirschsprung Disease

Epidemiology:
- Incidence 1 in 5000 live births
- Site of involvement:
- 75% confined to rectosigmoid
- 10% involvement of entire colon

Aetiology:
- Failure of ganglionic cell precursors to migrate into the distal bowel during fetal life
- Absence of ganglion cells from the myenteric and submucosal plexus (Meissner & Auerbach
plexus) of large bowel (due to failure of migration from the neural crest)
- This results in sustained contraction at aganglionic segment which is narrow and contracted
segment while distention and dilation of colon proximal to it.

Clinical features:
Symptoms Signs
Neonatal: - Distended abdomen
Early - Rectal examination
- Failure to pass meconium within first 24 hrs - Empty, contracted rectum clenches around
examiner`s finger (snug anal sphincter)
Late
- On finger withdrawal:
- Constipation from birth
- a gush of liquid stool expelled with flatus
- Abdominal distention
- Bilious vomiting
* May occur due to delay in diagnosis because
Children: temporary relief of obstruction as a result of
- Chronic constipation dilatation caused by rectal examination
- Abdominal distention
- Growth failure

Classification:
Short-segment Long-segment
- 5 males : 1 female - 1 male : 1 female
- Affects rectum and sigmoid - Extends above sigmoid
- 10-15% associate with Down`s syndrome

Complication:
- Hirschsprung enterocolitis
- Present during first few weeks of life: fever, foul-smelling diarrhoea, megacolon
- Severe and life-threatening
- Affected areas become thin & inflamed and may perforate
- Sometimes due to Clostridium difficile infection
Investigations:
Abdominal X-Ray - Dilatation of bowel
Rectal suction biopsy - Absence of ganglion cells in submucosal plexus
(1 & 3 cm above dentate line) - Excessive acetylcholinesterase (nerve trunk hyperplasia)
(Gold standard)
Anorectal manometry & - For surgeon to determine length of aganglionic area
barium study - Determine absence/presence of rectosphincteric reflux
- Not for diagnosis
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Management:
- Mainly surgical resection of the involved colon
- Initial colostomy above the aganglionic segment, followed weeks later by a transanal pull-
through excision of aganglionic bowel and creation of primary colorectal anastomosis without
laparotomy (limited to rectosigmoid involvement)

Differentiate functional constipation from Hirschsprung disease:


Functional constipation Hirschsprung disease
Onset Rare in infancy Common in infancy
Delayed passage of meconium Rare Common
Encopresis (involuntary defaecation) Common Unusual
Stool size Very large Small, ribbon-like
Failure to thrive Rare Common
Abdominal distention Variable Common
Painful defaecation Common Rare
Stool in rectal vault Common Rare
Anal tone Open, distended Tight

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Intussusception

Definition:
- Invagination of a segment of proximal bowel into the distal bowel in a `telescopic` manner

Epidemiology:
- Incidence is 1:1000 (Male : Female = 3 : 2)
- Commoner in children (2 months-2 years) than adults, peak at 6-9 months

Risk factor:
- Hypertrophy of Peyer`s patches (Lymphoid hyperplasia)
- Polyps
- Meckel`s diverticulum (eg. Peutz-Jeghers` syndrome, AD, hereditary intestinal polyposis)
- Intramural hematoma (eg. in Henoch Schonlein Purpura)
- Lymphosarcoma

Anatomy:
Common sites Parts of intussusception
- Ileocaecal - Intussuscipien (receiving part)
- Ileo-ileal - Intussusceptum (prolapse part)
- Ileo-ileocolic
- Jejunoileal
- Jejuno-jejunal

Pathophysiology:
- Intussusception progresses leading to prolonged obstruction
- As intussuscepted bowel is pulled further and further into downstream intestine by motility,
mesentery is pulled, stretched and compressed
- Venous outflow from intussusceptum is obstructed, leading to oedema, congestion & bleeding
- Third space fluid loss and `currant jelly` stools result

Clinical features:
Symptoms Signs
- Paroxysmal colicky abdominal pain - Abdominal distension
- Knees draw up, cry & appear pale - Sausage-shaped mass (RUQ or epigastrium)
- Colicky pain every 15-20 minutes - Signs of shock (tachycardia, hypotension)
- Bilious vomiting (prolonged obstruction) - Digital PR
- Refuse feeding, lethargy - Presence of blood or mucus
- Redcurrant jelly stool (blood + mucus)
(pathognomonic)
* Normal in between bouts of attacks

Complications:
- Small bowel obstruction (commonest)
- Mesenteric ischemia
- Perforation
- Peritonitis
- Sepsis
- Hypovolaemic shock (due to pooling of fluid in gut)

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Investigations:
Imaging Plain abdominal X-ray
- Typical gas distribution (crescent gas at the apex)
- Small bowel obstruction (distended small bowel + absence of gas in distal
colon or rectum)
USS & barium enema
- `doughtnut` or `target` appearance (layers of bowel wall of the end - on
intussusception)
- Present of free intraperitoneal fluid
Doppler Ultrasound (not routinely done)
- Check for bowel viability

Management:
- Fluid resuscitation (if patient in shock)
Conservative Operative
- Hydrostatic pressure or enema/air reduction - Laparoscopic or laparotomy (25%)
- Air insufflation - Open reduction
- 75% successful - Gentle retrograde reduction of the
- Partial or incomplete reduction may intussusceptum
warrant a repeat attempt after 4-6 hours - Surgical resection of bowel (10%)
- Indicated in failed open reduction or
gangrenous bowel
* Traction should not be applied to the proximal bowel

Indication for surgery:


- Concomitant peritonitis
- Radiological signs of perforation
- Failure of hydrostatic pressure reduction
- Presence of gangrenous bowel

Prognosis:
- Rapid recovery with resumption of oral feeding within 24-48 hours.
- Risk of recurrence: 1-2 %
- Mortality low if treatment started soon, high if resection is required (development of
gangrenous bowel)

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Pyloric Stenosis
Definition:
- Hypertrophy of longitudinal & circular smooth muscle of pylorus causing gastric outlet
obstruction (GOO)
Risk factor:
- Boys ( Male : Female = 4 : 1)
- First born
- Family history (particularly on the maternal side)
Clinical features:
Symptoms Signs
- Usually presents 2-7 weeks of age, irrespective
at - Do Test feed
of gestational age - For examination
- Calm the hungry infants
- Projectile vomiting
Inspection
- Not bile-stained
- Gastric peristalsis from left to right
- Increases in frequency & severity with time
Palpation
- Constant hunger (even after vomiting) - Pyloric mass or olive at the right upper quadrant
- Refuse only when markedly dehydrated (empty the air with nasogastric tube for
- Weight loss or poor weight gain examination if overdistension)
- In delayed presentation Auscultation
- Succussion splash (shake the infant`s abdomen)

Investigations:
Blood - BUSE: Low Cl (hypochloremia) & Low K+(hypokalemia)
- Serum HCO3-: Metabolic alkalosis (HCO3- increase to 25-35 mEq/L)
Radiology - Abdominal USS: Demonstrating hypertrophic pylorus
- Barium meal: Only perform when in doubt, grossly enlarged stomach
which empties slowly

Management:
Supportive Operative
- Correct fluid & electrolyte imbalance with IV fluid - Ramstedt`s pyloromyotomy
- Chloride and potassium should be replaced - Can be performed by laparotomy/laparoscopically
- Muscle of the pylorus is cut (NOT mucosa)
- Child can be fed the next day, discharge after 2-
3 days post-operatively

Ramstedt`s pyloromyotomy

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Malrotation & Volvulus
Introduction:
- Intestinal malrotation: Any variation caused by interruption of typical intestinal rotation and fixation
during fetal development
- Can occur at a wide range of locations leading to various acute & chronic presentations
- Most common type: Incomplete rotation predisposing to midgut volvulus (defined as abnormal twisting
of bowel at a focal point along its mesentery, different aetiology if occur in adult)

Common sites:
- Duodenojejunal flexure failing to rotate adequately to left around superior mesenteric vessels
- Caecum failing to rotate and descend on the right which may predispose to volvulus

Presentation:
Types Pathophysiology Presenting symptoms
Obtruction without Due to crossing of Ladd`s bands across - Bilious vomiting
compromised blood duodenum - Abdominal distension
supply - PR bleeding (late sign)
Obstruction with Due to volvulus of midgut around superior - Abdominal pain
compromised blood mesenteric vessels, supplying whole midgut - Abdominal distension
supply beyond ampulla of Vater to proximal 2/3 of
transverse colon → mesenteric ischaemia

Investigation:
Plain Abdominal X-Ray - All small bowel is to the right
- Distended stomach + proximal duodenum with rest of the abdomen
being gasless
Barium meal - Duodenojejunal junction to the right of the spine
- Duodenal obstruction often with spiral or corkscrew appearance
- Presence of small bowel mainly on the right side

Management:
Conservative Operative
- Fluid resuscitation & electrolyte correction - Reduction of volvulus
- Orogastric/nasogastric tube with 4 hourly - Resection of bowel (if gangrenous) with division
aspiration of Ladd`s band
- Antibiotics (if septic)

Picture below shows different anomalies associated with malrotation in newborns

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Meckel`s Diverticulum

Definition: Rule of 2s in Meckel`s:


- Ileal remnant of vitellointestinal duct (true diverticulum) - Occurs in 2% population
- Usually 5 cm long and found 60 cm from ileocaecal valve - 2-inches (5 cm) long
- Contains ectopic gastric & pancreatic mucosa - 2 feet (60 cm) from ileocaecal
valve
Epidemiology:
- 2/3 have ectopic mucosa
Occurs in 2% of population
(gastric and pancreatic)
Clinical features: - 2% becomes symptomatic
- Majority asymptomatic
- Most typical presentation is painless, severe rectal bleeding due to peptic ulceration
- Others:
- Diverticulitis : acute abdominal pain (differential diagnosis of acute appendicitis)
- Intussusception (leading to intestinal obstruction)
- Volvulus around a band

Investigations:
- Technetium scan/ Meckel scan (increase uptake by ectopic gastric mucosa 70%)
- Ultrasound, barium enteroclysis, video capsule endoscopy (visualise diverticula)
- Surgical exploration
Extra Notes:
Treatment: Omphalocele/Exomphalos (anterior abdominal wall defect
- Surgical resection in which intestine, liver & other organs remain outside
with membranous sac covering.
Gastrochisis (anterior abdominal wall defect which
abdominal contents freely protrude without membranous
Mesenteric Adenitis sac covering)
Introduction:
- Non-specific, self-limiting inflammation of mesenteric lymph nodes in RLQ
- Most common in children & adolescents (occasional encountered in adults)
- Yersinia enterocolitica is considered most common pathogen in temperate Europe, North
America & Australia, more common in boys
Aetiology:
- Viral or bacterial (Yersinia enterocolitica, Helicobacter jejuni, Campylobacter jejuni, Salmonella
spp, Shigella spp)
Clinical features:
- Acute abdominal pain (differential diagnosis of acute appendicitis)
- Often associate with systemic symptoms and signs including fever, headache, pharyngitis and
cervical lymphadenopathy
Management:
- Investigation (USS look for enlarged LNs, ileal/ileocaecal wall thickening>3mm over >5cm bowel)
- Symptomatic management (self-limiting)
- Conservative treatment
- Persistent right iliac fossa pain warrants surgical exploration to identify cause

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PART VII

UROLOGY
Renal Anomalies

Introduction:
- Frequent cause of renal failure in children (30% of ESRF)
- 3 categories based on the stage of primary abnormality in renal embryologic development:
Primary abnormality Examples
Failure to form a functional nephron - Renal agenesis
(renal parenchymal malformation) - Multicystic dysplastic kidney (MCDK)
Failure of migration of developing - Renal ectopy (Pelvic/ Thoracic kidneys)
kidney to appropriate destination - Abnormal fusion (Horseshoe kidney)
Defects of urinary collecting system - Double ureters (Duplex collecting system)
- Posterior urethral valves (PUV)
- The changes of renal parenchyma (hydronephrosis, dysplasia) are often secondary to
obstructive uropathy or urinary reflux disease
- Almost all abnomalies are detectable on antenatal ultrasound screening
- Inherited conditions include Polycystic Kidney Disease (PKD) are result of specific genetic
mutations detectable at birth or later in life

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A) Polycystic Kidney Disease (PKD)
- Group of genertically inherited conditions in which cyst formation and renal parenchymal
replacement occur anytime from fetal life
- Pathogenesis: ciliary dysfunction (PKD proteins are localised to cilia/basal body), loss/abnormal
cilia in the kidney are associated with cyst development
- 2 major forms: Autosomal Recessive (ARPKD) or Autosomal Dominant (ADPKD)
Autosomal Recessive Polycystic Kidney Disease Autosomal Dominant Polycystic Kidney Disease
- Commonly prenatal, neonatal, infantile, - Variable but commonly adulthood
juvenile, adolescence for age of presentation (40-50 years old)
(Presents early)
- Abnormal gene on short arm of Chr6 encodes - Abnormal PKD1 encodes Polycystin 1 (85%)
for Fibrocystin (polyductin) protein - Abnormal PKD2 encodes Polycystin 2 (15%)
- May associate with Potter sequence - May associate with Tuberous sclerosis (PKD1-
(oligohydramnios with lung hypoplasia, limb & TSC2 gene, contiguous gene syndrome)
facial abnomalities)
- Renal cysts are in radial pattern - Renal cyst are anywhere in kidney, varying size
- Cysts arise from collecting ducts & - Cysts arise from all types of tubules
perpendicular to cortical surface
- Presentation: mass at birth, interferes birth, - Presentation: flank pain, renal colic, mass,
respiration, renal failure haematuria, UTI, hypertension, renal failure
- Association: Biliary obstruction, congenital - Association: Liver cysts, pancreas cyst, vascular
hepatic fibrosis with portal hypertension, liver cyst (Berry aneurysm)
failure (cystic biliary dysgenesis) - Extrarenal manifestation are uncommon in child
- Complications: Oesophageal varices, GI bleeding - Complications: ESRF, stroke, male infertility
hypersplenism with thrombocytopenia, liver
failure, cholelithiasis, ascending cholangitis
- USS: Large kidneys (external surface lobulated), - USS: Progressive bilateral development &
increased echogenicity of parenchyma, loss of enlargement of focal cysts (increase size &
corticomedullary differentiation, macrocyst number with age), external surface smooth
- Diagnosis: - Diagnosis:
- +ve USS findings with - >1 cyst in child
- Absence of renal cysts in both parents - Parent with ADPKD
- Previously affected siblings
- Consanguinity
- Hepatic fibrosis
- Renal cysts do not communicate.
- Disease may present at any age, including prenatally.
- Gene defect leads to malfunction of the ciliary body.
- Both kidneys are usually enlarged, usually bilateral (except early diagnosis of ADPKD in childhood
with positive family history)

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B) Horseshoe Kidney
- Most prevalent fusion abnormality of developing kidney
- Commonly occurs at lower poles, 2 separate excretory
urinary system are maintained
- Isthmus may be located at/ lateral to midline (symmetric or
assymetric horseshoe kidney)
- May contain actual parenchyma or a fibrous band
- Physiology: Kidneys arrest embryologic ascension towards
dorsolumbar position usually between 4th to 9th weens POG
- Pathology: Inferior mesenteric artery holding isthmus and
preventing further rostral migration
- Blood supple is variable & may come from iliac arteries/
aorta, sometimes hypogastric & middle sacral arteries
- May occur isolated or associate with Turner, trisomy 18, less common (trisomy 13, 21)
- Associate with bicornuate/ septate uterus (girls) & hypospadias, undescended testis (boys)
- Most are asymptomatic & diagnosed incidentally by USS
- Symptoms: Pain, haematuria, obsturction, UTI, hydronephrosis (80%), urolithiasis (20%)
- Due to VUR, obstruction of collecting system or UPJ by external ureteric compression
- Patient with isolated case have slightly higher risk of developing Wilms tumour
- Investigation: Renal USS (hydronephrosis), MCUG (identify VUR), DTPA (obstruction)
- Management: Antibiotics & Surgical correction
C) Duplex collecting system
- Defined as 2 pyelocaliceal system within one renal
unit (both ureters may either drain separately or
jointly over a single orifice into bladder)
- Unilateral or bilateral (15-40%), associate with
congenital genitourinary tract abnormalities
- Common, 0.2% of live births
- Mostly asymptomatic, incidental finding
- Occurs when 2 ureteral buds arise from Wolffian duct
- Complete duplication:
- Upper renal unit: drains ectopically in bladder,
urethra (urinary dribbling,incontinence), vagina, uterus
- Lower renal unit: drains into ureteric insertion
- Investigations: renal USS, MCUS (identify VUR,
ureterocele, obstructive uropathy)
- Complications:
- Upper pole: Urinary obstruction from ectopic insertion
(hydronephrosis), ureterocele
- Lower pole: Urinary reflux (from maldevelopment of
ureter`s valve mechanism)
- Management: Surgical correction
D) Renal agenesis & Multicystic dysplastic kidney (MCDK)
- Renal agenesis: absence of both kidneys
- MCDK: failure of union of uteretic bud (which form ureter, pelvis, calyces, collecting ducts) with
nephrogenic mesenchyme (large fluid-filled cysts without renal tissue/ connection to bladder)

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Renal agenesis & MCDK (Non-functioning kidneys)

Reduced fetal urine excretion

Oligohydramnions causing fetal compression

Resulting in Potter's syndrome


- Potter facies: low set ears, beaked nose, prominent
epicathic fold and downward slanting eye, flat facies,
clubfoot
- Pulmonary hypoplasia: causing respiratory failure
- Limb deformity

E) Posterior urethral valve


- Most common cause of lower urinary tract obstruction
in male neonates
- Presence of congenital obstructing posterior urethral
membrane (COPUM)
- Valve classically seen on USS & MCUG (as a result of
perforation of COPUM by advancing Foley catheter)
- Abnormal intergration of Wolffian ducts into posterior
urethra lead to COPUM formation
- Related to impaired lung development in utero (Potter
sequence), bladder wall thickening & dilatation,
hydroureter, urinoma & hydronephrosis
- Obstructive uropathy result in renal dysplasia, renal
insufficiency, ESRF
- Voiding history important (usually have
diminising/abnormal urinary system)
- Treatment: PUV fulguration
- Complications: Post-obstructive diuresis (electrolyte
imbalance)
- Prognosis depends on degree of perserved renal
function after obstruction is relieved.

F) Absence musculature syndrome (Prune Belly syndrome)


- Severe deficiency of anterior abdominal wall muscle (wrinkled folds covering abdomen)
- Frequently associate with large bladder, dilated ureters & cryptorchidism

238
Renal Assessment

Glomerular filtration rate (GFR)


- Low in the newborn infant and is especially
low in premature infants
- GFR at 28 weeks Period of Gestation (POG) is
only 10% of term infant
- In term infants, the corrected GFR (15-20
ml/min per 1.73 m2) rapidly rises to 1-2 years
of age when the adult rate of 80-120 ml/min
per 1.73 m2 is achieved

Assessment of renal function in children:


Plasma creatinine Main test of renal function. Rises progressively throughout childhood according
concentration to height and muscle bulk. May not be outside laboratory `normal range` until
(PCr) renal function has fallen to less than half normal
Estimated The formula eGFR = k × height (cm) ÷ creatinine (μmol/L) provides estimate of
glomerular GFR. Better measure of renal function than creatinine and useful to monitor renal
filtration rate function serially in children with renal impairment (k is 40 if creatinine measured
(eGFR) using Jaffe method or 30 if measured enzymatically)
Inulin or EDTA More accurate as clearance from the plasma of substances freely filtered at the
glomerular glomerulus, and is not secreted or reabsorbed by the tubules. Need for repeated
filtration rate blood tests limits use in children
Creatinine Requires timed urine collection and blood tests. Rarely done in children as
clearance inconvenient and inaccurate
Plasma urea Increased in renal failure, often before creatinine starts rising, and raised levels
concentration may be symptomatic. Urea levels also increased by high protein diet and if in a
catabolic state.

Radiological investigations of kidneys and urinary tract:


Ultrasound (US) - Standard imaging procedure of the kidneys and urinary tract, provides
anatomical assessment but not function. Excellent at visualising urinary tract
dilatation, stones and nephrocalcinosis (small, multiple calcium deposits in renal
parenchyma)
- Advantages: non-invasive, mobile
- Disadvantages: operator-dependent, will not detect all renal scars
DMSA scan (99mTc - Static scan of the renal cortex
dimercaptosuccini - Detects functional defects, such as scars, but very sensitive, so need to wait at
c acid) least 2 months after a urinary tract infection to avoid diagnosing false `scars`
Micturating - Contrast introduced into bladder through urethral catheter.
cystourethrogram - Can visualise bladder and urethral anatomy. Detects vesicoureteric reflux (VUR)
(MCUG) and urethral obstruction
- Disadvantages: invasive and unpleasant investigation especially beyond
infancy, high radiation dose
MAG3 renogram - Dynamic scan, isotope-labelled substance MAG3 excreted from the blood into
(mercapto-acetyl- the urine. Measures drainage, best performed with a high urine flow.
triglycine, labelled - In children old enough to cooperate (usually >4 years), scan during micturition is
with 99mTc) used to identify VUR
Plain abdominal X- - Identifies unsuspected spinal abnormalities
ray - May identify renal stones, but poor at showing nephrocalcinosis.
239
Urinary Tract Infection (UTI)
Introduction:
- UTI is the growth of bacteria in the urinary tract
- Clinical manifestations of UTI include:
Clinical Pyelonephritis - Acute pyelonephritis is infections involving renal parenchyma with
(Upper UTI) fever > 38`C, can lead to pyelonephritic scarring
- Pyelitis is infections with no parenchymal involvement
- Involve any of these: abdominal/back/flank pain, fever, malaise,
nausea, vomiting, diarrhoea. Fever can be the only symptom
- Newborn has non-specific symptoms (poor feeding, irritability,
jaundice, weight loss)
- Most common serious bacterial infection in infants <2 years
- Xanthogranulomatous pyelonephritis (rare, granulomatous
inflammation with gaint cells & foamy histiocytes, manifest
clinically as a renal mass or acute/chronic infectio. Renal calculi,
obsruction & Proteus sp or E. coli infection as cause of lesion,
requires total/partial nephrectomy)
Acute Cystitis - Inflammation of bladder presenting with dysuria, urgency,
(Lower UTI) frequency, suprapubic pain, incontinence, malodorous urine
- No fever, not result in renal injury
- Acute haemorrhagic cystitis (often caused by E. coli while
adenovirus type 11, 21 more in boys, self-limiting, haematuria for
approximately 4 days)
- Eosinophilic cystitis (rare, multiple solid bladder masses consist
histologically of inflammatory infiltrates with eosinophils, ureteral
dilatation with hydronephrosis is common, may have allergen
exposure, treatment is usually antihistamine & NSAIDS)
- Interstitial cystitis (irritative voiding symptoms like urgency,
frequency, dysuria, bladder & pelvic pain relieved by voiding, -ve
urine culture, more in adolescent girls, diagnosis by cystoscopic
observation of mucosal ulcers with bladder distention, treatment
include bladder hypodistention, laser ablation of ulcerated area,
however no treatment provides sustained relief)
Asymptomatic bacteriuria - Condition when there is +ve urine culture but no symptoms of
infection, more common in girls, rare in boys
- Benign condition, no renal injury except in pregnant women,
which can lead to symptomatic UTI
- Great mimickers include day/night incontinence or perianal
discomfort 2` to UTI
Focal pyelonephritis - Acute lobar nephronia (acute lobar nephritis) is renal mass caused
`nephronia` by acute focal infection without liquefaction
(less common) - Early stage of development of renal abscess
- Identical manifestations as pyelonephritis
- CT shows nephromegaly without focal mass
Renal abscess - Renal abscess occurs following a pyelonephritic infection by
(less common) uropthogens or 2` to haematogenous infection (S. aureus)
- Perinephric abscess occurs 2` to contiguous infection in perirenal
area (eg. vertebral ostemyelitis, psoas abscess) or pyelonephritis
dissecting to the renal capsule

240
Definition:
Lower UTI Collective terms involving cystitis & urethritis
Upper UTI Collective terms involving pyelonephritis & renal abscess
Urosepsis Bacterial infection in urinary tract invade bloodstream to cause
septicaemia
Significant bacteriuria ≥105 cfu/mL of a single species of organism
Asymptomatic bacteriuria ≥105 cfu/mL of single species of organism without UTI symptoms
Sterile pyuria ≤104 cfu/mL, presence of pus cells with/without UTI symptoms or
pure/mixed growth of bacteria (seen in partially treated UTI, TB,
calculi, tumour)
Contaminated urine sample ≤104 cfu/mL or mixed culture
Recurrent UTI Same strain organism with rapid reinfection after cessation of
therapy within 2 weeks
Catheter-associated UTI Presence of UTI symptoms, ≥103 colony forming units of ≥1 bacterial
(CA-UTI) species in a single catheter urine specimen or in MSU from a patient
whose urethral, suprapubic or intermittent catheter removed within
previous 48 hours

Epidemiology:
- Occurs in 1% of boys & 1-3% of girls before age of 11 (50% have recurrence within a year)
- First year (M>F = 2.8-5.4:1), beyond 1-2 years (F>M = 10:1)
- In girls, first UTI is usually by age of 5, with peaks during infancy & toilet-training
- Comprises of 5% of febrile illness in early childhood
- Majority of cases of CKD in child are 2` to VUR or obstructive nephropathy which usually
associate with recurrent UTI

Aetiology:
E. coli - Commonest (85-90%), virulence depends on:
- Cell wall antigens (O,K,H antigens)
- Possession of endotoxins (haemolysin)
- P.fimbriae mediate attachment → pyelonephritis
Proteus - Common in boys, presence under prepuce
- Predisposes to formation of phosphate stone by urea-splitting mechanism →
ammonia → alkalising urine
Pseudomonas - Usually associated with structural abnormality in urinary tract affecting
drainage or catheter insertion (CA-UTI)
Klebsiella - More commonly found in hospital-acquired UTI due to their resistance to
antibiotics favours their selection in hospital
Enterococus - In neonate, UTI is due to haematogenous spread
- In older child, UTI is due to ascending spread (bowel organism colonise
periurethral area & adherence to uroepithelial cells)
S. saprophyticus - Present for both gender, more in adolescent girls (prone to be sexually active)

S. epidermidis - Associate with UTI in hospitalised patients (esp those with AIDS)

241
Risk factors:
- Divided into host defence mechanism & pathogen virulence
Host Pathogens
- Anatomy difference (female) - Bacterial infection
- Vesicoureteric reflux (developmental anomaly) - Enteric flora enter urinary tract via urethra
- Incomplete bladder emptying - Common organisms:
- Infrequent voiding, leads to bladder enlargement - E. coli
- Vulvitis - Proteus
- Hurried micturition - Pseudomonas
- Obstructive uropathy (constipation) - Pathogenicity (P fimbriae, capsular antigens,
- Neuropathic bladder (CP, spinal bifida) urease, haemolysin)
- Facilitation of entry of organism - Parasitic infection
- Uncircumcised male - Pinworm infestation
- Catheterisation - Fungi infection
- Surgery/instrumentation (cystoscopy) - Candida albican
- Behavioral activity - Immunocompromised patient
- Toilet training - Viral infection (rare)
- Wiping from back to front in girls - CMV, rubella (asymptomatic shedding in
- Tight clothing (underwear) congenitally-infected babies)
- Sexual activity - Adenovirus, BK virus (haemorrhagic cystitis in
- Pregnancy marrow transplant)
- Anatomy anomaly (labial adhesion)

Clinical features:
Newborn/Infant Older children
- Non-specific symptoms - May have specific urinary symptoms
- Fever, lethargy, irritability - Fever (chills & rigors), lethargy
- Vomitting - Frequency, secondary enuresis
- Diarrhea - Urgency/ hesistancy
- Prolonged jaundice - Dysuria/ scalding micturition
- Poor feeding, FTT - Suprapubic pain (cystitis) or loin pain
- Complications: - Cloudy & smelly urine
- Febrile convulsion (>6 months) - Anorexia, vomiting, diarrhea
- Irritability, photophobia, headache (meningitis) - Febrile convulsion
- Septicaemia
* Sometimes it is difficult to localise the site of infection whether upper or lower UTI
* The presence of UTI should be considered in children <2 years old with unexplained fever
* Pyelonephritis is normally presented with fever, loin pain while in cystitis, there is no fever, loin pain

Physical examination:
- General examination, growth, blood pressure
- Abdomen : Distended bladder, ballotable kidneys, other masses, genitalia, perineal hygiene
- Back : Spina bifida
- Lower limbs : Deformities, wasting of muscles (Neurogenic bladder)
Diagnosis:
An accurate diagnosis is extremely important as a false diagnosis of UTI will lead to unnecessary
interventions that are costly and potentially harmful. The quality of urine sample is of crucial
importance. Diagnosis is made when:
- Bacterial culture of ≥105 cfu/ml of a single organism OR
- Symptomatic + bacterial culture of 102 -104 cfu/ml of a single organism
242
Collection of urine:
Adhesive bag urine Applied to the perineum after careful washing, although there may
specimen be skin contamination. Positive culture should be confirmed with a
clean catch or suprapubic aspiration specimen
Clean catch specimen In a child who is bladder-trained. Sampling into a waiting clean pot
when the nappy is removed (recommended method)
Urethal If there is urgency in obtaining a sample and no urine has been
catheterisation passed, high sensitivity & specificity, lower risk of introducting
infections
Suprapubic aspiration Gold standard of obtaining an uncontaminated urine sample and
(SPA) any growth from SPA specimen is significant. It is usually done in
infants <1 year old, but also applicable in children up to 4-5 years
of age. Method : With the child lying in supine position, a fine
needle attached to a syringe is inserted directly into bladder 1-2 cm
above symphysis pubis under USS guidance (98% success rate) in
the midline. Urine is usually obtained at a depth of 2-3cm). It may
be used in severely ill infants requiring urgent diagnosis and
treatment, but considered invasive (increasingly replaced by
urethral catheter sampling)

Good method
- Suprapubic aspirate
- Catheter specimen
- Mid-stream specimen
- Clean catch specimen
- Bag urine specimen
Poor method

Investigations:
U-FEME + C&S - Should be microscoped and cultured straight away
- If there is delay in culture :
a) Refrigerate at 4`C (to prevent overgrowth of contaminating bacteria)
b) Add bacteriostatic agent (eg. Boric acid 1.8% or dipslides)
- UFEME diagnosis : Pyuria (>10 pus cell)
* Presence of WBC alone is not reliable (may lyse during storage or present
in febrile child without UTI in balanitis/vulvovaginitis)
- Culture diagnosis :
- ≥105 cfu/ml of single organism (90% specificity)
- Mixed organisms in the absence of WBC → Contamination
- For urine microscopy, WCC >10/ml (uncentrifuged) or >5/hpf (centrifuged)
is considered abnormal, can be false -ve in immunocompromised
Blood - FBC (leukocytosis, neutrophilia, ↑ESR, ↑CRP): non-specific for UTI
- ↑WCC >20,000-25,000/mm3 (suggestive of renal abscess)
- ↑Serum procalcitonin (pyenephritis, high risk of renal scarring)
- Blood culture (before initiating antibiotics)
Imaging - USS (reveal dilatation of upper tracts, renal size & major anomaly)
- MCUG (detect VUR or infravesical obstruction eg. posterior urethral valve)
(USS is done urgently, - 99mTc DMSA (uptake defect in early phase indicates inflammation, uptake
others for later stage) defect 6 months later indicates permanent scarring)
- MAG3 (only use in ureter dilatation without reflux, look for RAS, obstruction)
243
Studies show that 3 parameters in urinalysis (leukocyte esterase, nitrite, microscopy) carry highest sensitivity
and specificity in diagnosing UTI.

Management:
- After first proven UTI, antiobiotic therapy should be started without delay after collection of
satisfactory urine specimen, together with ultrasound of kidney & urinary tract
- In patients with high risk of serious illness, it is preferable that urine sample should be obtained
first; however treatment should be started if urine sample is unobtainable.
- Oral antibiotic is satisfactory in a non-toxic child. The usual choices include trimethoprim
or cephalosporin. Agents that are excreted in the urine but do not achieve therapeutic
concentrations on the blood stream (eg. Nalidixic acid or nitrofurantoin) should not be used
to treat UTI in febrile infants and young children with likely renal involvement
- Patients with toxic appearing/unable to retain oral intake should receive parenteral antibiotic
- Duration of treatment: 7-14 days. Always review antibiotic when urine C&S results are available
- Repeat urine culture after 2 days of treatment. Bacteriuria is almost always eradicated within
24-48 hours of introducing effective treatment. Change antibiotic if bacteriuria persists.
- Children treated for UTI should continue antibiotic at prophylactic dosage while awaiting
hospital referral and imaging studies

Drug Therapy Prophylaxis


Trimethoprim 4 mg/kg/dose bd 1-2 mg/kg nocte
Nitrofurantoin* 1 mg/kg/dose qtd 1 mg/kg nocte
Amoxycillin 20-40 mg/kg/dose tds
Amikacin 15 mg/kg/dose od
Gentamicin 5 mg/kg/dose od
Cephalexin 50-100 mg/kg/day in 4 dose 5 mg/kg nocte
* Must check G6PD status

Prevention of UTI
- Aim : - To ensure washout of organism that ascend into the bladder
- To reduce the presence of aggressive organism
- High fluid intake to produce a high urine output
- Regular voiding
- Ensure complete bladder emptying (double micturition)
- Prevention of constipation
- Good perineum hygiene
- Antibiotic prophylaxis
- Lactobacillus acidophilus (probiotics to encourage colonisation of gut to reduce number of
pathogenic organisms which potentially cause invasive disease
244
Factors predisposing to renal scarring/damage
- Antenatal renal anomality
- Infant & boy
- Delayed treatment of UTI, recurrent UTI
- Septicemia
- Severe grades of reflux
- Host susceptibility, bacterial virulence

Antibiotic prophylaxis:
- Should not be routinely recommended in infants and children following first time UTI as
antimicrobial prophylaxis does not seem to reduce significantly the rates of recurrence of
pyelonephritis, regardless of age or degree of reflux.
- However, antibiotic prophylaxis may be considered in the following:
- Infants and children with recurrent symptomatic UTI
- Infants and children with vesico-ureteric reflux grades of at least grade III

Antibiotic Treatment for UTI:


Type of Infection Preferred Treatment Alternative Treatment
UTI (Acute cystitis)
E.coli. PO Trimethoprim 4mg/kg/dose bd PO Trimethoprim/ Sulphamethazole
Proteus spp. (max 300mg daily) for 1 week 4mg/kg/dose (TMP) bd for1 week
- Cephalexin, cefuroxime can also be used especially in children who had prior antibiotics.
- Single dose of antibiotic therapy not recommended.
Upper Tract UTI (Acute pyelonephritis)
E.coli. IV Cefotaxime 100mg/kg/day q8h for IV Cefuroxime 100mg/kg/day q8h OR
Proteus spp. 10-14 days IV Gentamicin 5-7mg/kg/day daily
- Repeat culture within 48hours if poor response.
- Antibiotic may need to be changed according to sensitivity.
- Suggest to continue intravenous antibiotic until child is afebrile for 2-3 days and then switch to
appropriate oral therapy after culture results e.g. Cefuroxime, for total of 10-14 days.
Asymptomatic bacteriuria
No treatment recommended
Antibiotic Prophylaxis for UTI
Indication Preferred Treatment Alternative Treatment
UTI Prophylaxis PO Trimethoprim 1-2mg/kg ON PO Nitrofurantoin 1-2mg/kg ON OR
PO Cephalexin 5mg/kg ON
- Antibiotic prophylaxis is not be routinely recommended in children with UTI.
- Prophylactic antibiotics should be given for 3 days with MCUG done on the second day.
- A child develops an infection while on prophylactic medication, treatment should be with a different
antibiotic and not a higher dose of the same prophylactic antibiotic.

Measures to reduce risk of further infections


- Dysfunctional elimination syndrome (DES) or dysfunctional voiding is defined as an abnormal
pattern of voiding of unknown aetiology characterised by faecal and/or urinary incontinence
and withholding of both urine and faeces
- Treatment: high fibre diet, use of laxatives, timed frequent voiding, regular bowel movement
- If condition persists, referral to a paediatric urologist/nephrologist is needed

245
Recommendations for imaging
Previous guidelines have recommended routine radiological imaging for all children with UTI.
Current evidence has narrowed indications for imaging as below:
Ultrasound Recommended in
- All children less than 3 years of age
- Children above 3 years of age with poor urinary stream, seriously ill
with UTI, palpable abdominal masses, raised serum creatinine, non
E coli UTI, febrile after 48 hours of antibiotic or recurrent UTI
Should be done urgently TRO obstruction or pus collection
DMSA scan Recommended in infants and children with UTI with any of the
following features:
- Seriously ill with UTI
- Poor urine flow
- Abdominal or bladder mass
- Raised creatinine
- Septicaemia
- Failure to respond to suitable antibiotics within 48 hours
- Infection with non E. coli organisms
MCUG Routine MCUG after first UTI should not be recommended, may be
considered in:
- Infants with recurrent UTI
- Infants with UTI and the following features:
- poor urinary stream, seriously ill with UTI, palpable abdominal
masses, raised serum creatinine, non E. coli , UTI, febrile after 48
hours of antibiotic treatment
- Children less than 3 years old with the following features:
- Dilatation on ultrasound
- Poor urine flow
- Non E. coli infection
- Family history of VUR
Done when children is free from infection, usually 6 weeks after an
acute infection
Others DTPA scan (Tc-99m diethylene-triamine-penta-acetic acid scan)
MCUG in older children (depend on USS findings)

Recommendation for Imaging:


0-2 years old - USS, DMSA & MCUG
2-5 years old - USS & DMSA
- MCUG if USS & DMSA abnormal or child has severe or recurrent
infection or family history of reflux
>5 years old - USS
- MCUG if USS abnormal or child has recurrent infection
* DMSA/MCUG usually done 4-6 weeks after initial UTI

246
Further Management
This depends upon the results of investigation
Normal renal tracts - Prophylactic antibiotic not required
- Urine culture during any febrile illness or if the child is unwell
Renal scarring without VUR - Repeat DMSA 6-12 months later to ensure defect is a real scar
and not pyelonephritis
- Repeat urine culture only if symptomatic
- Assessment includes height, weight, blood pressure and
routine tests for proteinuria
- Children with a minor, unilateral renal scarring do not need
long-term follow-up unless recurrent UTI or family history or
lifestyle risk factors for hypertension
- Annual BP surveillance for life
- Annual renal function test and UFEME (for proteinuria) if
bilateral or severe scarring
- Children with bilateral renal abnormalities, impaired renal
function, raised blood pressure and or proteinuria should be
managed by a nephrologist
- Close follow up during pregnancy
Vesicoureteric reflux (VUR) - Refer VUR topic
Posterior urethral valve - Refer urologist/surgeon
Renal dysplasia, hypoplasia - May need further imaging to evaluate function and drainage.
or evidence of obstruction - Refer surgeon if necessary.
- Monitor renal function, BP, and growth parameters

- Intrarenal reflux. MCUG in an infant with a past history of UTI


- Note the right vesicoureteral reflux with ureteral dilation, with
opacification of renal parenchymal representing intrarenal
reflux

- DMSA scan showing bilateral renal scarring, more severe on left


upper lobe

247
Vesicoureteric Reflux (VUR)
Definition:
- Retrograde flow of urine from the bladder up to the ureter and collecting system
Aetiology:
Primary VUR Secondary VUR
- Congenital incompetence of ureterovesical (UV) - Distal bladder obstruction (BOO)
junction (commonest) - Increased intravesicular pressure from cystitis or
- Ureter is displaced laterally and enter directly acquired bladder obstruction
into the bladder rather than at an angle - Posterior urethral valve (urethral obstruction)
- Shorten intramural course - Neuropathic blader (50%)
- Familial (30-40% in first-degree relatives) - Voiding dysfunction
- Duplication of ureters with/without ureterocele
- May obstruct upper collecting system
- Often lower pole of duplicated renal unit
- Post-UTI (temporary) or recurrent UTI

Clinical features:
- Commonest radiological abnormality in children with UTI (30-40%)
- Children with VUR are at risk for further episodes of pyelonephritis with potential for increasing
renal scarring and renal impairment (Reflux nephropathy)
ESRF (End stage
renal failure)

Recurrent Progresssive
VUR
UTI renal
Hypertension

* Backflow of urine from the renal pelvic into the papillary collecting duct → high risk of renal scarring

Investigations:
Renal ultrasound (RUS) - Evaluate urinary tract for hydronephrosis, scarring
Micturating cystourethrogram - Detect urethral/ bladder abnormalities
(MCUG) - Detect VUR
- Provides additional anatomic detail as compared to NCG
- Indicated when RUS reveals findings suggestive of VUR or there is a
recurrence of febrile UTI
Radionuclide cystogram (NCG) - Same as MCUG but able to detect mild VUR with less radiation
Dimercaptosuccinic acid - Reliable test for diagnosis of acute pyelonephritis
(DMSA) - Detection of renal scarring
Nuclear renal scanning - Identify renal scarring

Complications:
Incomplete bladder emptying - Urine return into bladder after voiding
- Predisposes to UTI
Pyelonephritis - Particularly if there is intrarenal reflux
Chronic kidney disease (CKD) - Occur when voiding pressure is high & transmitted to renal papillae
- Segmental glomerulosclerosis with interstitial scarring → shrunken,
poorly functioning segment of kidney (if severe & bilateral) → renal
failure & HPT
Hypertension - Renal scarring causing decreased renal function, fluid retention
248
Classification of VUR Severity (International Reflux Study Committee)

Grade 1 Into a non-dilated ureter


Grade 2 Into the pelvis and calyces without dilation
Grade 3 Mild to moderate dilation of the ureter, renal pelvis, and calyces with minimal blunting of
the fornices
Grade 4 Moderate ureteral tortuosity and dilation of the pelvis and calyces
Grade 5 Gross dilation of the ureter, pelvis, and calyces; loss of papillary impressions; and ureteral
tortuosity

Management:
- Most reflux resolves spontaneously with time (grade 1 to 2 - 80%; grade 3 - 50%; grade 4 - 25%)
- Studies have not shown any significant difference in outcome between both medical & surgical
intervention
Medical Surgical
- Long-term prophylactic antibiotic therapy - Ureteral reimplantation/ dextranomer/
- TMX or nitrofurantoin hyaluronic acid copolymer (Deflux procedure)
- Maintain sterile urine until - Very successful minimally invasive correction of
- At least 4-5 years old (based on fact that new mild to moderate VUR
scars have only rarely been seen to develop - Considered if:
after 4-5 years but optimal duration is not yet - Antibiotic prophylaxis fails to prevent
well-defined) breakthrough infection
- Reflux has resolved spontaneously - New scar formation
- Useful in children with high-grade VUR or - Non-compliance to medical prophylaxis
recurrent symptomatic UTI - Persisting high grade (4 to 5) VUR beyond 2
years especially in girls
- Immediate treatment for any breakthrough
infection
- Periodic urine culture (approximately every 3
months) to detect asymptomatic bacteriuria as
well as culture when a fever is present
Additional
- Advice on general measure to prevent recurrent UTI
- Follow up patients with renal scarring (refer UTI section)
- Sibling screening (High risk group would be siblings younger than 5 years of age, evidence of AD)
* For mild reflux (grade 1 and 2), discontinuing prophylaxis after age 2 years. If DMSA scan shows
scarring; repeat 1 year later. If DMSA scan normal, can discharge.
Medical management is the treatment choice for
- All infant (regardless of the reflux grade)
- Older children with mild to moderate VUR (grade 1-3) who can be maintained infection-free
249
Haemolytic Uraemic Syndrome (HUS)
Introduction:
- Characterised by triad: microangiopathic haemolytic anaemia, thrombocytopenia, renal injury
- Important cause of AKI in children (occurs in <5 years of age but can occur in older child)
- Most common type is associated with prodromal diarrhoeal illness (D+HUS)
Aetiology:
- Contamination of meat, fruit, vegetables or water with verotoxin(VT)-producing E.coli O157:H7
or Shigella → inactivate ADAMTS13→microthrombi→ haemorrhagic enterocolitis → HUS
- Atypical HUS (without prodromal diarrhoea) is more severe than D+HUS, can be 2` to infection
(Strep Pneumoniae, HIV), genetic & acquired defects in complement regulation, medication, SLE
Clinical features:
Symptoms Signs
Prodromal phase: - Pallor (microangiopathic haemolytic anaemia)
- Diarrhoea - Irritability
- Bloody stools (enterocolitis) - Petechiae (thrombocytopenia)
- Signs of dehydration
Acute phase (7-10 days later): - Hypertension (volume overload/AKI)
- Weakness, lethargy - CNS signs: seizures (25%), encephalopathy
- Abdominal pain - Other organs:
- Oliguria/anuria (AKI) - Pancreatitis
- Haematuria - Cardiac dysfunction
- Bleeding tendency (thrombocytopenia) - Colonic perforation
* Suspect child without diarrhoea with microangiopathic syndrome as TTP (predominant CNS symptoms with
significant renal disease, recurrence is common, but difficult to distinguish from HUS in some cases)

Investigation:
Blood - Normochromic, normocytic anaemia (MAHA)
- Thrombocytopenia
- Leukocytosis
- Increased LDH, decreased hatoglobin (breakdown of RBCs)
- Elevated reticulocyte count (RR)
- LFT: Increased unconjugated bilirubin, Increased AST
- RP: Elevated creatinine
PBF - Presence of schistocytes, helmet cells, burr cells
Urinalysis - Presence of haematuria, proteinuria, pyuria, casts
Others - Positive stool culture for E.coli O157 : H7
- Positive stool test for shiga-toxin
- Elevated amylase/ lipase
- Coombs test negative
- D-dimer normal (TRO SLE, consumptive coagulopathy)

Management:
Supportive Managing complications
- Volume repletion (early hydration for diarrhoea) - Dialysis (indicated if uncorrected renal
- Control of hypertension insufficiency)
- AVOID antibiotics, antidiarrhoeal - RBC transfusion
(as they may increase risk of developing HUS) - Platelet transfusion (NOT use unless in active
haemorrhage as it might worsen thrombotic
microangiopathy)

250
Proteinuria
- Defined as urine protein > 40 mg/m2/hr or >1 g/m2/day OR
- Early morning urine protein: creatinine index > 200 mg/mmol (3.5 mg/mg)
A) Physiological/ Transient Proteinuria
- Causes include:
- Orthostatic (eg. proteinuria only when standing upright, normal when recumbent)
- Exercise induced (transient)
- Febrile (transient)
B) Pathological/ Persistent Proteinuria
- Confirmed by repeated urine dipstick then quantified by 24 hrs urine collection or measuring
urine protein/creatinine ratio in an early morning sample (Protein should not >20 mg/mmol Cr)
- Causes include:
Tubular proteinuria - Hereditary tubular dysfunction
- Acquired tubular dysfunction
Glomerular disease - Minimal change disease
- Glomerulonephritis
- Abnormal glomerular basement membrane (familial nephritides)
Vascular disease - Hypertension (increased glomerular perfusion pressure)
Others - UTI - Reduced renal mass
- Drugs - Urinary calculi
- Tumours (eg. lymphoma)
- Usually asymptomatic and may appear frothy urine
- Most common symptoms of renal impairment
- Primary detection is by urine dipstick (can detect >100-200mg/L, react primarily with albumin)

Haematuria
- Indication of bleeding from anywhere in urinary tract (RBC should not present in normal urine)
- Red-coloured urine or postitive test for Hb on urine dipstick (>10 RBC/hpf)
Macroscopic - Visible & reported as red urine by patient
- If seen at initial voiding, becomes clear later (urethra, prostate, bladder neck)
- If diffuse at voiding (bladder, ureter, kidneys) * Brown urine for glomerular
- If seen at end of voiding (prostate, bladder base)
Microscopic - Detected by urine dipstick (detection limit: 15-20,000 RBC/ml)
- Can be false +ve for haemoglobinuria or myoglobinuria
- Always followed by urine microscopy (+phase contrast) to confirm presence
of RBC (red cell cast suggestive of bleeding from kidneys, most often dt GN)
- Causes:
Non-glomerular Glomerular
- Infection (bacterial, viral, TB, schistosomiasis) - Acute GN (usually with proteinuria)
- Trauma (genitalia, urinary tract, kidneys) - Chronic GN (usually with proteinuria)
- Stones - IgA nephropathy
- Tumours - Familial nephritis (eg. Alport syndrome)
- Sickle cell disease - Thin GBM disease
- Bleeding disorders
* GBM is -ve charge & permeability depends on size &
- Renal vein thrombosis charge molecules
- Hypercalciuria
* Renal biopsy indicated when RP abnormal, persistent ↑complements, recurrent macroscopic hematuria
or significant persistent proteinuria

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Acute Glomerulonephritis (AGN)
Definition:
- Specific set of renal disease which immunological mechanism triggers inflammation and
proliferation of glomerular tissue
- Antigen-antibody complexes in the glomerular basement membrane (GBM) induces
complement activation
- Initiates glomerular proliferation and inflammatory response
Epidemiology:
Most common in the younger age group
Aetiology:
Exogenous Endogenous
- Post-streptococcal infections* - Autoimmune diseases
- Pharyngitis - Henoch Schonlein purpura
- Skin infection (eg. impetigo) - Systemic lupus erythematosus (SLE)
- Bacterial infection/Sepsis - Wegener`s Granulomatosis
- Subacute bacterial endocarditis - Polyarteritis Nodosa (PAN)
- Drugs - Hemolytic Uremic Syndrome
- Heavy Metal - IgA Nephropathy
- MembranoprolIferative GN
- Hereditary nephritis
- Goodpasture syndrome (anti-GBM ds)
* Most common cause in children (6-10 years old) & developing world, usually caused by Group A β-hemolytic
streptococci

Post-Streptococcal AGN
Pathogenesis:
- Immunological in nature
- Bacteria become trapped in the glomerulus → Acute diffuse proliferative GN
- Formation of immune complex → Deposited in the glomerular capillary (evoke inflammatory
response → Complement activation) → Damage to GBM → Hematuria & Proteinuria
- Increased glomerular cellularity restricts glomerular blood flow & therefore glomerular
filtration rate (GFR) decreases → Reduced urine output & fluid retention → Pulmonary oedema
& HTN (can lead to seizures)
Clinical Features:
- Post-streptococcal GN develops after 1-2 weeks of streptococcal infection
Symptoms Signs
Specific Cardinal Features of AGN
- Edema (Periorbital, pedal & scrotal) - Oedema
- Facial puffiness is an early sign - Hematuria (micro/macroscopic)
- Smoky or tea-coloured urine (haematuria) - +/- proteinuria
- Reduced urine output - Uraemia (azotemia)
Non-Specific - Oliguria
- Anorexia & lethargy - Hypertension
- Abdominal Pain General
Complications: - Hypertension
- SOB (pulmonary oedema) - Papilloedema (fundoscopy)
- Dizziness, headache (hypertensive encephalopathy) - Skin lesions (eg. impetigo, cellulitis)
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Complications:
CNS - Hypertensive encephalopathy
Early - Restless, drowsy
- Headache
Late - Visual disturbance
- Vomiting, nausea
- Seizures, Coma

Respiratory System - Pulmonary oedema


Renal - Nephrotic syndrome, rapidly progressive GN
- Irreversible renal failure
Blood - Severe uraemia
- Hyperkalemia [K+] > 5.5 mmol/L
- Kussmaul`s breathing due to metabolic acidosis
- Cardiac arrest (due to cardiac arrhythmia)

K – Ketones (DKA)
U – Uraemia
S – Sepsis
S – Salicylates
M – Methanol
A – Aldehydes
L – Lactic acidosis

Diagnosis:
- Detailed history (evidence of a recent streptococcus infection (culture of the organism)
- Raised ASOT and low C3 level that return to normal after 3-4 weeks
- ASOT (Antibody to Streptolysin-O titre) - Post-streptococcal GN
- ANCA (Anti-neutrophil cytoplasmic antibody) - Goodpasture synd
Investigations:
Urinalysis & Culture - Hematuria (RBC distorted and fragmented)
- Proteinuria (usually trace up to 2+ but if >2+ need to consider nephrotic
syndrome)
- RBC casts (pathognomonic for AGN) & other cellular cast
- Pyuria may also be present
Bacteriological & - Raised ASOT (>200 IU/ml)
serological evidence - Increased anti-DNAse B (if available) - better serological marker of preceding
of antecedent strep. streptococcal skin infection
Infection - Throat swab or skin swab
Blood - FBC (↑WCC for evidence of infection)
- Renal Profile
- Blood urea, serum creatinine (assess renal function, ↓GFR)
- Electrolytes (look for electrolyte imbalance)
- Complement levels
- C3 level is low at onset of symptoms and normalize by 6 weeks
- C4 level is usually within normal limits in post streptococcal AGN
- Immunological markers
- Antinuclear & anti-dsDNA antibody (SLE)
- ANCA (for Wegener`s granulomatosis & polyarteritis)

253
Imaging - CXR (look for cavitation in Wegener`s granulomatosis)
- Renal ultrasound & biopsy
- Indication of renal biopsy:
- Steriod-resistant, atypical presentation or severe acute renal failure
- Prior history of renal disease or family history of nephritis
- Features suggesting non post-infectious AGN as cause of acute nephritis
- Delay resolution:
- Oliguria > 2weeks
- Azotemia > 3 weeks
- Gross haematuria > 3 weeks
- Persistent haematuria > 6 months

Management:
- Divided into supportive & specific management
A) Supportive Management:
- Strict monitoring
- Fluid intake, urine output, daily weight, BP (nephrotic chart)
- Penicillin V for 10 days to eliminate β-haemolytic streptococcal infection (give erythromycin if
penicillin is contraindicated)
- Fluid restriction to control edema and circulatory overload during oliguric phase until child diureses
and BP is controlled
- Day 1 : Up to 400 mls/m2/day. Omit if child has clear signs of fluid overload eg. pulmonary oedema
- Day 2 : Till patient diureses - 400 mls/m2/day (as long as patient remains in circulatory overload)
- When child is in diuresis - free fluid is allowed
- Diuretics (eg. Furosemide) should be given in children with pulmonary oedema, it is usually needed
for treatment of hypertension
- Diet: Salt free! Protein restriction is unnecessary
- Look out for HTN and complications of Post-streptococcal AGN:
- Hypertensive encephalopathy
- Pulmonary edema (acute left ventricular failure)
- Acute renal failure
- Indication for dialysis:
- APO, Hyperkalemia, severe acidosis, uraemic symptoms

B) Specific Management:
Infection - Antibiotic (oral penicillin ×10 days) to eliminate β-haemolytic Streptococcal
infection
Edema - Diuretic eg. frusemide may be useful for treatment of hypertension and if fluid
retention has not improved with fluid restriction
Hypertension Significant hypertension but asymptomatic
① Nifedipine - Bed test and recheck BP 30 min later
② Frusemide - If BP still high, give oral nifedipine 0.25-0.5 mg/kg. Recheck BP 30 min later
③ Captopril - Monitor BP hourly ×4 hours the 4 hours if stable
④ Metoprolol - Oral nifedipine can be repeated if necessary on prn basis.
- May consider regular oral nifedipine (6-8 hourly) if BP persistently high
- Add frusemide 1mg/kg/dose if BP still not well controlled
- Other anti-hypertensives-captopril (0.1-0.5 mg/kg 8 hourly); Metoprolol 1-
4mg/kg 12 hourly

254
Symptomatic/severe hypertension/hypertensive emergency/ hypertensive
encephalopathy
- Symptom/ sign: headache, vomiting, loss of vision, convulsions, papilloedema
- Emergency management is indicated to reduce BP sufficiently to avoid
hypertensive complications yet to maintain it at a level that permits
autoregulatory mechanism of vital organs to function.
- Reduce mean BP [DBP + 1/3(SBP - DBP)] by 25% over 3-12 hours then next 75%
reduction is achieved over 48 hours
Severe acute - Severe persistent oliguria or anuria with azotaemia is uncommon
kidney injury - Peritoneal dialysis
- Hemodialysis
Hyperkalemia - IV calcium gluconate
- Protect myocardium from hyperkalemia
- IV insulin with dextrose
- To drive potassium into cells
- IV sodium bicarbonate
- To connect acidosis
- Resonium (oral or rectal)
Pulmonary - Sit-up & give high flow O2 by face mask
edema - Venous vasodilator (eg. morphine) (+ metoclopramide: antiemetic)
- IV diuretics (eg. frusemide)
- IV nitrates also can be used
- If no response consider hemodialysis

Antihypertensive drug used for hypertensive emergency in children


Drug Dose
Nifedipine 0.25-0.5 mg/kg/dose oral, may be repeated twice if no response. Caution with the
sublingual route
Sodium Nitroprusside 0.5-1.0 mcg/kg/min, iv infusion, may increased stepwise to 8.0 mcg/kg/ min max.
Need to be given in the ICU setting. Caution in liver and renal failure.
Labetolol 0.2-1.0 mg/kg/dose, by repeated iv boluses OR 0.25 – 2.0 mg/kg/hour by iv
infusion.
Hydralazine 0.2-0.4 mg/kg/dose by iv bolus, may be repeated twice if no response.

When to discharge?
Criteria for discharging patients:
- Weight drop
- Renal function improved
- HTN resolved
Follow up: (if proteinuria and hematuria has fully resolved)
- Follow up for at least 1 yr at 1-3 months interval
- Do U-FEME (and renal function if initially abnormal) to evaluate recovery
- Monitor BP at every visit
Prognosis:
- Proteinuria and oedema characteristically decline rapidly by 5-10 days
- Hypertension and gross hematuria normally resolves by 2-3 weeks
- C3 returns to normal by 6-8 weeks, Microscopic hematuria persist for months to a year
- Generally EXCELLENT prognosis, self limiting disease with >95% recover completely but
minority of patient progress to renal failure disease

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Natural history of Acute Post-Streptococcal GN:

Familial Nephritis (Alport syndrome)


- X-linked recessive disorder that progresses to ESRF, family history of nephritis
- Characterised by glomerulonephritis, ESRF, bilateral sensorineural hearing loss
- Others: cataracts, lenticonus, keratoconus, retinal flecks in macula, proteinuria, haematuria
- Macrothrombocytopenia or granulocytic inclusions; Diffuse leiomyomatosis of oesophagus/
female genitalia
- Management: Symptomatic, ACE-I (↓proteinuria), dialysis, renal transplant(may fail: rejectance)

Vasculitis
- Includes HSP, PAN, microscopic polyarteritis & Wegener granulomatosis
- Clinical features: Fever, malaise, weight loss, skin rash, arthropathy
- Diagnosis:
- ANCA(anti-neutrophil cytoplasmic Antibody)
- Renal arteriography (to demonstrate aneurysm in PAN)
- Management:
- Steroids, plasma exchange & IV cyclophosphamide

Systemic Lupus Erythromatosus (SLE)


- Manifests as lupus nephritis
- Diagnosis is made from renal biopsy
- Management: Steriod or Cyclophosphamide (for steriod-resistant)
Primary & Secondary Causes of Renal Disease in Children:
Primary Secondary (Systemic)
- Minimal change nephrotic syndrome - Post-infectious GN
- Focal segmental glomerulosclerosis - IgA nephropathy
- Membranoproliferative GN - Henoch-Schonlein purpura-related nephritis
- Membranous nephropathy - Membranoproliferative GN
- Congenital nephrotic syndrome - HUS, SLE, Wegener`s granulomatosis, other
- Alport syndrome vasculitides
- Intrinsic tubular disorders - Tubular toxins
- Structural renal disorders - Antibiotics, Chemotherapeutic agents
- Congenital urinary tract abnormalities - Haemoglobin/myoglobin
- Polycystic kidney disease - Tubular disorders
- Renal/urinary tract tumour - Cystinosis, oxalosis
- Galactosemia, heritary fructose intolerance
- Stones (calculi)
- Sickle cell disease/trait
- Trauma
- Extrarenal malignancy (leukaemia, lymphoma)
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Nephrotic Syndrome
Introduction:
- Clinical syndrome of massive proteinuria defined by:
- Oedema (Increased ECF)
- Proteinuria
- 24-hour urine protein >40 mg/m2/hour or >1g/m2/day
- Early morning/spot urine protein: creatinine index of >200 mg/mmol (>3.5 mg/mg)
- Hypoalbuminaemia (<25 g/L)
- Hypercholesterolaemia (>250 mg/dL) or Hyperlipoproteinaemia (>10 mmol/L)
Epidemiology:
- Incidence is 16/100,000 children
- M : F ratio = 2 : 1
- 85-90% of children, proteinuria resolve with steroid & do not progress to renal failure
Aetiology:
Primary Secondary
- Congenital (family history of Alport Syndrome, - Autoimmune disease
renal failure, renal transplant) - Henoch-Schonlein purpura
- Primary focal glomerulosclerosis - Wegener & other vasculitides
- Primary idiopathic nephrotic syndrome - SLE
- Minimal change disease (<5 y/o) - Diabetes (eg. diabetes nephropathy)
- 85-90% of cases - Amyloidosis (usually adults)
- Antecedent URTI & prevalent in patients with - Chornic infections (eg. Hepatitis B, C, HIV, AGN,
family hx of atopic diseases malaria)
- Histology: - Allergens (eg. bee sting)
- Glomeruli are normal or minimal increase in - Amyloidosis
mesangial cells - Drugs (eg. corticosteroids, diuretics, ACE
- EM - podocyte fusion Inhibitor, NSAIDs)
- Congestive heart failure, constrictive pericarditis
- Renal vein thrombosis
- Malignancies

Pathophysiology:
- Believed to be an immunological event but precise pathway still unknown
- Hallmark: Heavy proteinuria
- Selective permeability to albumin of the glomerular capillary
- There are two hypotheses:
- Change in the anionic composition of the GBM (albumin is negatively charged)
- Flattening, retraction and effacement of the foot podocytes

Proteinuria (↑ glomerular permeability), hypoalbuminemia (↓ plasma oncotic pressure)

Oedema (salt & water move to extravascular compartment due to ↑ hydrostatic pressure) +
Activation of renin-angiotensin aldosterone system

Promotes sodium & water reabsorption in the distal nephron

Hypovolemia → Hyperviscosity *
(↓ synthesis of antithrombin, protein C, protein S)
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Hyperlipidaemia
- Increased cholesterol and triglyceride synthesis following increased hepatic albumin synthesis
- Urinary loss of enzyme digesting cholesterol

* Virchow`s triad: hypercoagulability, endothelial injury, Blood flow (turbulent)

Types of Nephrotic Syndrome


- Minimal Change Glomerular Lesion (Steroid sensitive NS – commonest type)
- Focal Segmental Glomerulosclerosis
- Membranoproliferative/ Mesangiocapillary GN Steroid Resistant NS
- Membranous Nephropathy

Clinical features:
Symptoms Signs
- Facial swelling (earliest) - Periorbital oedema
- Breathlessness (due to pleural effusions & - Scrotal, leg, sacral & pedal oedema
abdominal distension) - Ascites
- Abdominal pain & diarrhea (lethargy) - Signs of pleural effusion
- Decreased urine output - Ipsilateral reduced chest expansion
- Hypertension (<15%) - may be atypical NS - `Stony dull` to percussion
- Absent breath sounds or bronchial breath
sound just above the effusion

Complications:
Hypovolemia - Due to oedema (water and sodium moves into third space)
- Clinical Features: abdominal pain & syncope (peripheral vasoconstriction)
- Investigations:
- Low urinary sodium (<20mmol/L)
- High PCV
- SHOCK & THROMBOSIS (commonly renal vein thrombosis)
Thrombosis - Urinary losses of antithrombin increased blood viscosity
- Increased synthesis of clotting factors by steroid thrombosis
Infection - Urinary losses of immunoglobulin (susceptible to infection particularly
Pneumococcus)
- Steroid therapy (immunosuppression)
- Generalised edema - good for bacterial culture medium
- eg. Spontaneous Bacterial Peritonitis (SBP), cellulitis, URTI
Hypercholestrolemia - As explained above
Renal Failure - <5% develops RF (NOT for minimal change ds)

Differential diagnosis of an oedematous child


- Allergic reaction
- Congenital Heart Disease (CCF)
- Chronic Liver Disease
- Protein Losing Enteropathy/ Malnutrition

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Investigations:
Blood - FBC (Hb, WCC & Hct)
- Evidence of infection & hemoconcentration
- ESR
- BUSE + Creatinine
- LFT (Look for hypoalbuminemia <25g/L)
- Serum complement level (↓C3 & C4 in AGN)
- Serum ASOT & anti-DNAse B
- Hepatitis B
Urine - Urine dipstick (albustix) for proteinuria
- 24-hour urine collection (in older children)
- U-FEME (if +ve) + C & S
- Urinary sodium concentration
- Low sodium (<20mmol/L) indicates hypovolemia
Renal Biopsy - Not indicated for idiopathic syndrome in children prior to starting corticosteroid
therapy
- Main indication is
- Steroid resistant nephrotic syndrome*
- Presence of atypical features such as persistent hypertension, gross hematuria
Imaging - Renal ultrasound/CT/MRI (TRO renal vein thrombosis if indicated)
* Define as failure to achieve remission despite 4 weeks of adequate corticosteroid therapy

Management:
1) Management of the oedematous state
Bed rest - Not required & usually not practical unless the child has gross oedema
Diet - A normal protein diet with adequate calories is recommended
- No added salt to the diet during the oedematous state
Antibiotics - Penicillin V 125mg BD (1-5 y/o); 250mg BD (6-12 y/o); 500mg BD (>12y/o) is
recommended during relapse particularly with gross oedema
Fluid status - Carefully assess the haemodynamic status
- Check for signs and symptoms which may indicate
- Hypovolaemia (abdominal pain, cold peripheries, tachycardia and poor pulse
volume, low blood pressure) OR
- Hypervolaemia (basal lung crepitations and rhonchi, hypertension)
Fluid restriction - Not usually recommended except in oedematous state
Diuretics - eg. frusemide is not usually necessary in steroid responsive nephrotic syndrome
but if required should be used with caution as it can precipitate hypovolaemia
Human albumin - 0.5-1.0 g/kg can be used in symptomatic grossly oedematous states together with
(20-25%) IV frusemide at 1-2 mg/kg to produce a diuresis
- Caution: fluid overload and pulmonary oedema with salt poor albumin infusion.
Urine output and blood pressure should be closely monitored
- Human albumin at 0.5-1.0 g/kg of 5%, 20% or 25% (which ever is available) over
one hour in those suspected to have hypovolaemia/underfilled state. Do not give
frusemide in this instant.
Chart - Input/Output chart
monitoring - Nephrotic chart

2) Management of complications of nephrotic syndrome


Hypovolemia - Clinical features: abdominal pain, cold peripheries, poor pulse volume, hypotension
& haemoconcentration
- Treatment: infuse salt poor albumin at 0.5 to 1.0g/kg/dose over one hour. If salt-

259
poor albumin is not available, other volume expanders like 5% albumin, plasma
protein derivatives or human plasma can be used
Primary - Clinical Features: fever, abdominal pain in children with frank nephrotic syndrome
peritonitis (SBP) - Investigations: Blood culture, peritoneal fluid culture (not usually done)
- Treatment: parenteral penicillin and a third generation cephalosporin
Thrombosis - Detailed investigation & adequate treatment with anticoagulation is needed

3) General Advice
- Inform regarding high probability (85-95%) of relapse.
- Home urine albumin monitoring. Urine dipstick testing of the first urine specimen in the
morning daily. Parents are advised to consult doctor if albuminuria >2+ for 3 consecutive days
- Immunocompromised status eg. steroid therapy
- Parents and children should be advised & cautioned for contact with chicken pox and measles,
and if exposed should be treated like any immunocompromised child
- Immunization: While the child is on corticosteroid treatment and within 6 weeks after its
cessation, only killed vaccines may safely be administered to the child. Live vaccines can be
administered six weeks after cessation of corticosteroid therapy
- Acute Adrenal Crisis
- This may be seen in children who have been on long term corticosteroid therapy (equivalent
to 18mg/m² of cortisone daily) when they undergo situations of stress. Prevention and
- Treatment: corticosteroids (hydrocortisone) given in 3 divided doses at 2-4 mg/kg/dose
4) Corticosteriod therapy
- Corticosteroids is effective in inducing remission of nephrotic syndrome but the most optimal
dose & duration is yet to be resolved although it has been found that longer duration results in
more prolonged remission
- Prednisolone dosage at:
- 60 mg/m²/day (maximum 80mg/day) for 4 weeks
- Followed by 40mg/ m²/EOD (maximum 60mg) for 4 weeks
- Then reduced prednisolone dose by 25% monthly over next 4 months
- 90% of children will achieve remission defined as urine dipstick is trace or nil for 3 consecutive
day within 28 days, many within 7-14 days
- Definition:
Steriod-sensitive - Age between 1-10 years old
nephrotic syndrome - No macroscopic haematuria
- Normal BP, complement, renal function
Steriod-resistant - Failure to achieve response to an initial 4 weeks treatment with prednisolone
nephrotic syndrome 60mg/m²/day
- Should be referred to a nephrologist for a renal biopsy

5) Management of relapse
- Majority of children with nephrotic syndrome will relapse.
- Definition: Urine albumin excretion >40mg/m²/hour or urine dipstix of 2+ or more for 3
consecutive days
- Treatment: Prednisolone 60 mg/m²/day until remission then 40 mg/m²/EOD for 4 weeks & off
- Breakthrough proteinuria may occur with intercurrent infection and usually does not require
prednisolone if the child has no edema remains well and the proteinuria resolves with
resolution of the infection. If proteinuria persists, treat as relapse.

260
6) Management of frequent relapse
- Definition: ≥2 relapses within 6 months of initial response or ≥4 relapses within any 12 months
- Treatment:
- Prednisolone 60 mg/m²/day till urine albumin nil/trace for 3 days (until remission)
- Prednisolone 40 mg/m²/alternate morning for 4 weeks only
- Taper prednisolone dose every 2 weeks and keep on as low alternate day dose as possible for
6 months. Should a child relapse while on low dose alternate day prednisolone, the child
should be re-induced as for a relapse.
7) Management of Steriod-dependent Nephrotic Syndrome
- Definition: 2 consecutive relapses occurring during the period of steroid taper or within 14 days
of its cessation
- Treatment:
- If the child is not steroid toxic, re-induce with steroids and maintain on as low a dose of
alternate day prednisolone as possible
- If the child is steroid toxic (short stature, striae, cataracts, severe cushingoid features)
consider cyclophosphamide therapy
8) Cyclophosphamide therapy
- Indicated for the treatment of steroid dependent nephrotic syndrome with sign of steroid
toxicity & should be started when child is in remission following induction with corticosteroids
- Dose: 2-3 mg/kg/day for 8-12 weeks
- Monitoring: FBC and U-FEME two weekly
9) Relapse post-Cyclophosphamide
- Relapses after a course of cyclophosphamide is treated as for relapses after the initial diagnosis
of nephrotic syndrome if the child does not exhibit any further signs of steroid toxicity
- Should relapse occur soon after a course of cyclophosphamide when the child is still steroid
toxic, or the child again becomes steroid toxic after multiple relapses then a paediatric
nephrology opinion should be sought
- Treatment options available include cyclosporine & levamisole
10) Steroid-resistant nephrotic syndrome
- Refer for renal biopsy, specific treatment will depend on the histopathology
- General management of nephrotic state:
- Control of edema
- Restriction of dietary sodium
- Diuretic eg. Frusemide, Spironolactone
- ACE inhibitor (eg. captopril) or ARB (eg. Losartan, Irbesartan) to reduce proteinuria
- Monitor BP & renal profile 1-2 weeks after initiation of ACE inhibitor or ARB
- Control of hypertension using anti-hypertensive of choice
- Penicillin prophylaxis
- Monitor renal function
- Nutrition: normal dietary protein content, salt-restricted diet
- Evaluate calcium & phosphate metabolism
Prognosis:
- 93%-97% respond to steroid therapy (steroid-sensitive)
- 1/3 resolve, 1/3 relapse infrequently, 1/3 relapse frequently
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- <5% develop renal failure
Summary of Treatment of Nephrotic Syndrome:

Side effects of CORTICOSTERIODS:


C - Cushing syndrome
O - Osteoporosis
R - Retardation of growth
T - Thinning of skin & easy bruising
I - Infections & immunosuppression
C - Cataract & glaucoma
O - Oedema
S - Suppression of hypothalamic-pituitary-
adrenal axis
T - Thinning & ulceration of gastric mucosa
E - Emotional disturbance
R - Rise in BP (hypertension)
O - Others (fetal abnormalities, hypokalemia)
I - Increase in hair growth (hirsutism)
D - DM precipitation
S - Striae (abdominal)

Definitions:
Remission - Urine dipstick is trace or nil for 2 consecutive days within 28 days
Relapse - Urinary albumin excretion > 40mg/ m²/hour OR
- Urine dipstix ≥ 2+ for 3 consecutive days
Frequent relapse - ≥ 2 relapses in 6 months of initial diagnosis OR
- ≥ 4 relapses within any 12 months period
Infrequent relapse - Anything less than frequent
Steroid-resistant - Failure to achieve remission in spite of 4 weeks treatment with prednisolone at
60 mg/m2/day (standard steriod therapy)
Steroid- - ≥ 2 consecutive relapses during period of steroid tapering or within 14 days of
dependance steriod cessation


262

PART VIII

HAEMATOLOGY
Haemopoiesis

- Maintain lifeling production of haemopoietic cells


- Main sites in fetal life are yolk sac (0-2 mths), liver & spleen (2-7 mths) [postnatal: bone marrow]
- All haemopoietic cells derived from pluripotent haemopoietic stem cells
- Deficiency causes bone marrow faliure (stem cells require for ongoing replacement of cells)
- Stem cell transplantation (cells from healthy donor into children with marrow failure)
- Embryonic haemoglobin Haemoglobin type Globin chains
(Hb Gower 1, Gower 2, Portland) α-gene cluster β-gene cluster
are produced between 4-8 weeks Embryonic
POG, after which Hb production Hb Gower 1 ξ2 ε2
switches to fetal Hb (HbF), main Hb Gower 2 α2 ε2
Hb during fetal life, higher affinity Hb Portland ξ2 γ2
for oxygen than adult Hb (HbA), Fetal
thus advantage in relative hypoxic HbF α2 γ2
environment of fetus. Adult
- At birth, HbF, HbA and HbA2 HbA α2 β2
gradually replaced by HbA and HbA2 α2 δ2
HbA2 during first year of life Haemoglobin types in newborns and adults
- Increased HbF proportions in Newborn HbF 74%, HbA 25%, HbA2 1%
healthy children is a sensitive Children >1 year old and HbA 97%, HbA2 2%,
indicator of haemoglobinopathies adults HbF (0.5-0.8%)
- Stores of iron, folic acid, vitamin
B12 in term & preterm babies are adequate at birth. However, in preterm infants, stores of iron
& folic acid are lower and depleted more quickly, leading to deficiency after 204 months if
recommended daily intakes are not maintained by supplements.
- Hb concentration is high at birth (>14g/dl) but falls to its lowest level at 2 months of age
- White blood cells in neonates are higher than in older children (10-25x109/L)
- Platelet counts at birth are within the normal adult range (150-400x109/L)

Haematological values during infancy, childhood & adulthood: (Nelson)

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Anaemia in Children

Definition:
- Hemoglobin level below the normal range for a child of that age and gender (WHO)
Age Non-anaemic Mild anaemia Moderate anaemia Severe anaemia
6 - 59 months ≥11.0 10.0 - 10.9 7.0 - 9.9 <7.0
5 - 11 years ≥11.5 11.0 - 11.4 8.0 - 10.9 <8.0
12-14 years ≥12.0 11.0 - 11.9 8.0 - 10.9 <8.0

- Variation in FBC indices with age:


Age Hb (g/dL) RBC (x10^12/L) MCV (fl)
Birth 14.9-23.7 3.7-6.5 100-135
2 months 9.4-13.0 3.1-4.3 84-105
12 months 11.3-14.1 4.1-5.3 71-85
2-6 years 11.5-13.5 3.9-5.3 75-87
6-12 years 11.5-15.5 4.0-5.2 77-95
12-18 yr girls 12.0-16.0 4.1-5.1 78-95
12-18 yr boys 13.0-16.0 4.5-5.3 78-95
In general: MCV (mean corpuscular volume): 80-95 fL
MCH (mean corpuscular haemoglobin): 27-34 pg
MCHC (mean corpuscular haemoglobin concentration): 30-35 g/dL

Physiology: (Refer Haemopoiesis for more details)


- In fetus, blood contains predominantly HbF (fetal Hb), therefore O2 dissociation curve is shifted
to left (high affinity for O2)
- Hb concentration in newborn is 15-23 g/dL
- Minimum level is at 2-3 months of age (lower limit is 9.5 g/dL) because of erythroid hypoplasia
of bone marrow, ↓in blood volume & change of HbF→HbA (from late fetal life to 6-month age)
Aetiology (Classification according to mechanism):
- Anaemia results from one or more of the following mechanisms: (anaemia of prematurity: >1 mechanism)
A) Reduced RBC production:
- Ineffective erythropoiesis
- Iron deficiency (commonest cause of anaemia)
- Folic acid deficiency
- Chronic inflammation (juvenile idiopathic arthritis)
- Rarities (myelodysplasia, lead poisoning)
- Red cell aplasia
- Congenital red cell aplasia/Diamond-Blackfan anaemia (complete absence RBC production)
- Parvovirus B19 infection
- Transient erythroblastopenia of childhood
- Rarities (Fanconi anaemia, aplastic anaemia, leukaemia)
B) Increased RBC destruction: (haemolysis)
- RBC membrane disorders (Hereditary Spherocytosis, Hereditary Elliptocytosis)
- RBC enzyme disorders (G6PD)
- Haemoglobinopathies (Thalassaemia, Sickle-cell disease)
- Immune (Haemolytic disease of the newborn, AIHA)
C) Blood loss: (relatively uncommon cause in children)
- Fetomaternal bleeding
- Chronic gastrointestinal blood loss (Meckel`s diverticulum)
- Inherited bleeding disorders (vWD)

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Aetiology (Classification according to age groups):

Neonates
Severe Less severe
Antepartum Antepartum
- Rh isoimmunisation (usually with jaundice) - ABO incompabilities
- Twin-twin transfusion syndrome - Kell & Duffy
- Feto-maternal transfusion
- Abruptio placentae

Intrapartum/ Postpartum
- Hemorrhage

Infants or childhood
Type Examples
Haemolytic anaemia
Intracorpuscular factor Extracorpuscular factor
- Hemoglobinopathies - Autoimmune hemolytic anaemia
- Sickle cell anemia (Coomb`s test +ve)
- Thalassemia - Primary
- Red cell enzyme deficiency - Infection (CMV, HIV, viral hepatitis,
- G6PD deficiency infectious mononucleosis,
- Pyruvate kinase deficiency mycoplasma, typhoid fever,
- Red cell membrane defect malaria)
- Spherocytosis - Drug: penicillin
- Congenital dyserythropoietic - Collagen disease: SLE
anemia - Heavy metals
- Hypertension

Deficiency anaemia
- Nutritional anemia
- Iron deficiency anemia
- Folate or very rarely vitamin B12 deficiency
- Malabsorption syndrome
- Celiac disease

Bone marrow failure


Primary Secondary
Congenital: - Drug (antibiotic, cytotoxic,
- Fanconi`s anemia convulsion)
- Congenital pure red cell aplasia - Post-infection (viral hepatitis, EBV,
(Diamond-Blackfan anemia) parvovirus)
- Irradiation
Acquired:
- Bone marrow infiltration (leukemia,
- Aplastic anemia
lymphoma, neuroblastoma)
- Transient erythroblastopenia of
childhood (TEC)

Blood loss

265
Acute Chronic
- Trauma - Parasites (eg. hookworm)
- GIT - Bleeding disorders
- GERD - Hemophilia
- Meckel`s diverticulum - von Willebrand`s disease
- Cow`s milk protein intolerance
- Menstruation in adolescent
- Epistaxis
- Iatrogenic (eg. excessive
venesection in infants)

Anaemia of chronic - Chronic inflammatory disorders


disease - Juvenile idiopathic arthritis
- Organ failure (eg. ESRF)
- Hypothyroidism

Clinical features:
Symptoms Signs
- Pale - Pallor, jaundice
- Lethargy & tiredness - Tachycardia, tachypnea
- Anorexia - Collapsing pulse, bounding pulse
- Reduced effort tolerance - Flow murmur
- Associate with jaundice - Bleeding site, ecchymosis
- Reduced activity - Hepatosplenomegaly
- Hematemesis, hematochezia - Lymphadenopathy
- Signs of iron-deficiency anemia:
(koilonychia, angular stomatitis, glossitis)
- Signs of cardiac failure:
(tachycardia, tachypnea, cardiomegaly,
bibasal crepitations)

Simple Diagnostic Approach to Anaemia in Children:

Hb HPLC Findings:

Sickle-cell:
- HbS present
- No HbA

β-Thal major:
- Only HbF present

β-Thal minor:
- Increased HbA2

α-Thal trait:
- Hb HPLC normal

266
Physical Findings in Evaluation of Anaemia:

267
Summary for Aetiology of Anaemia:

Differential Diagnosis of Anaemia with/without Generalised Lymphadenopathy/Hepatosplenomegaly:


Presence Absence
- Acute/ chronic leukaemia - Acute blood loss
- Chronic haemolytic anamia - Iron-deficiency
- Thalassaemia - Folate deficiency
- Hereditary Spherocytosis/ Elliptocytosis - B12 deficiency
- G6PD deficiency - Acute haemolytic anaemia
- Malignancies (eg. lymphoma) - G6PD deficiency with oxidant stress
- Chronic infection (eg. TB) - Autoimmune
- ABO incompatibility
- Infection (eg. Malaria)
- Drug-induced
- Bone marrow failure (Aplastic/Fanconi`s anaemia)
- Others (Hypothyrodism, Chronic renal failure)
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Iron-deficiency Anaemia

Introduction:
- Commonest deficiency disease in the world at present.
- Commonest cause of anemia in childhood
- Prevalence is higher in poorer socioeconomic groups.
- Incidence of iron deficiency anemia in most reported series appears to be related to not age,
sex, or race, but to socioeconomic factors.
- Inadequate intake of iron is common in infants as additional iron is required for the increase in
blood volume accompanying growth and to build up the child`s iron stores
- May develop because of a delay in introduction of mixed feeding beyond 6 months of age or to
a diet with insufficient iron-rich foods, especially if it contains a large amount of cow`s milk
- Iron absorption
- Markedly increased when eaten with food rich in vitC (fresh fruit & vegetables)
- Inhibited by tannin (tea) Iron content in food:

Iron sources:
- For infants, iron may come from:
- Breastmilk (low iron content but 50% of the iron is
absorbed)
- Infant formula (supplemented with adequate iron)
- Cow`s milk (higher iron content than breastmilk, only
10% is absorbed)
- Solids introduced at weaning (eg. cereals:
supplemented with iron but only 1% is absorbed)

Aetiology:
- Chronic blood loss
- Meckel's diverticulum, peptic ulcer, ITP, parasitic infection, hemoglobinuria, polyp
- Increased demand - prematurity/low-birth weight infant and rapid rate of growth
- Frequently poor dietary intake of iron
- Impaired absorption - Malabsorption, chronic diarrhea, GI abnormalities, hookworm infection

Laboratory findings:
- Red cell indices
-↓Hb (hypochromic , microcytic RBC, Anisopoikilocytosis, +/- target cell)
-↓MCV
-↓MCH
- Low serum ferritin
- Stool for occult blood loss and ova and cyst for parasitic infections

Management:
- Nutritional counseling
- Advice on diet
- Maintain breastfeeding
- Use iron fortified cereals
- Iron supplementation
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- Oral iron medication: 6mg/kg/day of elemental iron in 3 divided doses for 6-8 weeks after
hemoglobin level is restored to normal. Syrup FAC (ferrous ammonium citrate): 1mg elemental
iron per ml. Ferrous fumarate/sulphate tablet: 200mg elemental iron per tablet.
- Consider the following for failure to respond to oral iron:
- Non-compliance
- Inadequate iron dosage
- Unrecognised blood loss
- Incorrect diagnosis
- Impaired GI absorption
- Blood transfusion: In general no transfusion required in chronic anemia unless there are signs
of decompensation (e.g.: cardiac dysfunction) and the patient is otherwise debilitated. Give
low volume packed cells (<5ml/kg) if necessary over 4-6 hours with IV furosemide (1mg/kg) in
severe anemia (Hb <4g/dL)
- For 6-year-old patients, blood transfusion is indicated if Hb< 6mg/dL or emergency. If patient's
condition is stable, consider 20ml/kg in 1 day.

Iron requirements during childhood:

270
Thalassaemia
Definition:
Hemoglobinopathies are genetic disorders which result from either the synthesis or abnormal
Hb chain (Hb variant) or defective synthesis of normal Hb chain (thalassemia syndrome)

Introduction:
- Inherited defects of globin chain synthesis
- Results from alteration (absence/reduce) in the genes controlling the globin chain production
- Excess of other globin chains → Precipitate within red cell membrane → Cell death within bone
marrow (ineffective erythropoiesis) & premature removal of circulating red cell by spleen
(shortened RBC survival) → Hypochromic and microcytic anaemia
α-Thalassemia Reduced rate of α-chain synthesis (chromosome 16)
β-thalassemia Reduced rate of β-chain synthesis (chromosome 11)
* Chromosome 11 - ε,γ,β,δ ; Chromosome 16 - α,ζ
- Common presenting symptoms are pallor, lethargy, FTT & hepatosplenomegaly

Epidemiology:
- β-thal major is an inherited blood disorder presenting with anaemia at 4-6 months of age
- In Malaysia, β-thal carrier rate is estimated at 3-5%, most of whom are unaware of their carrier/
thal minor status
- Carrier rates of α-thal & HbE are 1.8-7.5% and 5-46% respectively (HbE are found more in
northern peninsular states)
- Interaction between a β-thal carrier with a HbE carrier may result in birth of patient with HbE/β-
thal or thal intermedia with variable clinical severity (moderate-severe forms behave like β-thal
major patients while the milder forms are asymptomatic)

Types of Haemoglobin:
Hb Structure Comments
Normal A α2β2 - 97% of adult haemoglobin
A1c α2β2 - ≤5% of HbA (glycosylated Hb)
A2 α2δ2 - 2% of adult haemoglobin (↑in β-thal)
F α2γ2 - Normal Hb in fetus from 3-9 months, ↑in β-thal
Abnormal chain H β4 - Found in α-thal
production Barts γ4 - Found in homozygous α-thal, incompatible with life
Abnormal chain S α2β2 - Substitution of valine by glutamate in position 6 of β chain
structure C α2β2 - Substitution of lysine by glutamate in position 6 of β chain
* There are 4 α gene & 2 β gene for globin synthesis

- Diagnosis of Thalassaemia involves both clinical & laboratory diagnosis


- Laboratory diagnosis involves screening tests and diagnostic tests:
- Screening test:
- MCH (<27 pg) & MCV (<80 fl)
* MCH preferable as it is less susceptible to storage changes (But Hb Constant Spring have normal MCV, MCH)
- RDW (normal in thal trait, increased in iron-deficiency CV>14%, thal-intermedia, thal major)
- Diagnostic test:
- High performance liquid chromatography (HPLC) – quantify HbA2, HbF
- Low serum ferritin (α-thal is considered when iron-deficiency is excluded & HbA2 is normal)
- Haemoglobin electrophoresis
- Other tests: PBF, H-inclusion test, Kleihauer test, Sickle solubility test
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A) β-Thalassaemia

Epidemiology:
- Commonest in people from Mediterranean and Middle East
- Common in Chinese and Malays in Malaysia

Diagnostic criteria for β-Thalassaemia:


Types Clinical Diagnosis Laboratory Diagnosis
β-Thalassaemia minor - Normal to mild anaemia - Hb (>10 g/dL)
(trait) - No organomegaly - MCH (<27 pg)
- HbF(2.5-5%)
- Asymptomaptic
heterozygous carrier - HbA2 (4-9%) [HbE trait if >20%]
- HbA >90%
β-Thalassaemia - Milder anaemia - Hb (8-10 g/dL)
intermedia/ HbE Thal (presented after 2 years old, not require - MCH (<27 pg)
regular transfusion, require when - HbF(>10%)
fulminant infections, pregnancy, oxidant - HbA2 (4-9%) [HbE if >10%]
drug use) - HbA (5-90%)
- Thalassaemia facies - HbH disease (presence of H band)
- Hepatosplenomegaly
β-Thalassaemia major - Severe anaemia - Hb (<7 g/dL)
(Cooley`s anaemia) (Present usually at 4-6 months or child - MCH (<27 pg)
younger than 2 years old, require regular - HbF (>90%)
- Homozygous β- blood transfusion+iron chelation therapy) - HbA2 (normal or high)
thalassaemia - Hepatosplenomegaly - HbA (usually absent)
- Jaundice
- Thalassaemia facies
- Growth failure/ mental retardation

During pregnancy, β-thalassemia major does not affect the fetus due to HbF. When a baby is born in the first 6
months of life it is gradually replaced with HbA. Thalassemic children are unable to produce enough HbA, he/she
is usually well at birth and become ill in later life. So, the HbF is increased in that patient.

Clinical features:
General - Pallor (anemia)
- Jaundice (due to hypersplenism, ↑ RBC destruction)
- Failure to thrive or retarded growth
- Delayed puberty
Thalassaemia - Skull bossing (prominent frontal & parietal bones)
facies (bony - Maxillary overgrowth
deformities) - Prominent malar eminence
(hypoxia - bone marrow expand inside the bones → bone weak & alter shape →
make more & more non-functional RBC → RBC dies easily)
GIT - Hepatosplenomegaly
- due to resumption of hematopoiesis (extramedullary hematopoiesis)
- Gallstones (↑ bile pigments) *cholecystectomy if biliary colic/obstructive jaundice
CVS - Cardiomegaly
- Recurrent leg ulcers
Hypersplenism
- Splenomegaly with normal function of bone marrow
- Pancytopenia (anaemia, leukopenia, thrombocytopenia) caused by enhanced capacity of splenic
pooling, sequestration and destruction of blood cells, leading to ↑ plasma volume
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Investigations:
Blood - FBC
- ↓Hb, MCH, MCV - hypochromic microcytic anaemia)
- ↑ Reticulocyte count (RR)
- RDW (normal in thal trait, raised in iron-deficiency, thal intermedia, thal major)
- PBF
- Anisopoikilocytosis (including fragments & tear-drop cells)
- Hypochromia, microcytosis
- Basophilic strippling
- Pappenheimer bodies & Target cells
- Iron status (TRO iron-deficiency anaemia or identify iron overload in thal major)
High performance - Precise quantification of HbA2,HbF with presumptive identification of variant Hb
liquid - Diagnostic for β-Thal in accurate determination of ↑HbA2
chromatography - HbA2 (4-9%) in heterozygosity or severe β-Thal
(HPLC) - HbA2 (3.6-4.2%) in mild β-Thal
- Correction required for HbA2 to quantify Hb subtypes (falsely lowed by iron
deficiency)
Hb Electrophoresis - Screening for abnormal Hb
- Increaed HbF (α2γ2) & HbA2 (α2δ2>4%)
- Markedly low HbA (α2β2)
- H inclusion test for α-Thal
DNA analysis - Confirmatory test by identify globin chain synthesis & structural analysis
- Diagnostic test for α-Thal
- Required when unable to confirm haemoglobinopathy by haematological tests
- Genetic counseling & prenatal diagnosis

Baseline investigations to be done for all new thalassaemia patients:


- Full blood count and peripheral blood film (In typical cases, the Hb would be <7g/dL)
- Hb electrophoresis/ HPLC (β-Thal major: HbA decreased or absent, HbF increased, HbA2 variable)
- HbA decreased or absent
- HbF increased
- HbA2 variable
- Serum ferritin
- Red cell phenotyping (ideal) before first transfusion
- DNA analysis (optional)
- indicated for confirmation of difficult cases, used in prenatal diagnosis and detection of α carrier
(available at IMR, HUKM, UMMC and USM)
- Liver function test
- Infective screening - HIV, Hepatitis B & C, VDRL screen (before first transfusion)
- HLA typing (for all patient with unaffected siblings)
- All nuclear family members must be investigated by Hb electrophoresis for genetic counseling
- 1st & 2nd degree relatives should be encouraged to be screened & counselled (cascade screening)

Management:
- Algorithm for management of transfusion-dependent thalassaemia patients (CPG 2009) involves:
- Family cascade screening, Genetic counseling, Dietary advice
- Blood transfusion therapy
- Iron chelation therapy
- Monitor for complications
- Transfusion-related complications (HepB, HepC, HIV)
- Iron overload (serum ferritin, liver iron concentration, cardiac T2)
- Target-organ damage (cardiac, endocrine, hypersplenism, infections)
- Consider stem cell transplantation (when has unaffected siblings)

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1) Blood transfusion therapy
- Aim: suppress extramedullary haemopoiesis while minimising complications from transfusion
and maintaining normal well-being

β-Thalassaemia Major
- Indications:
- After completing blood investigations for confirmation of diagnosis
- Hb <7 g/dL on 2 occasions > 2 weeks apart (in absence other factors eg. infection)
- Hb >7 g/dL in β-Thal major/severe forms of HbE-β Thal if impaired growth, para-spinal
masses, severe bone changes, hepatosplenomegaly
- Transfusion targets:
- Maintain pre-transfusion Hb level at 9 -10 g/dl
- Aim to keep mean post-transfusion Hb at 13.5-15.5g/dl
- Aim to keep mean Hb 12 - 12.5 g/dl
- Not advisable to raise the post-transfusion Hb above 15.5g/dL
- High-transfusion regime (never allow to fall <10g/dL)
- Above targets allow for normal physical activity and growth, abolishes chronic hypoxaemia,
reduce compensatory marrow hyperplasia which causes irreversible facial bone changes and
para-spinal masses
- Transfusion interval:
- Usually 4 weekly interval (usual rate of Hb decline is at 1g/dl/week)
- Interval varies from individual patients (range: 2-6 weekly)
- Transfusion volume:
- Volume: 15-20mls/kg (maximum) packed red cells (PRBC)
- Round-up to the nearest pint of cross-matched blood provided
- If calculated volume is just >1 pint of blood, give 1 pint
- If calculated volume is just < 2 pints, give 2 pints
- This strategy minimizes the number of exposure to immunologically different units of blood
product and avoid wastage of donated blood
Note:
- In the presence of cardiac failure or Hb < 5g/dl, use lower volume PRBC (< 5ml/kg) at slow infusion
rate over >4 hours with IV Frusemide 1 mg/kg (20 mg maximum dose)
- It is recommended for patients to use leucodepleted (pre-storage, post storage or bedside leucocyte
filters to prevent non-haemolytic febrile reachtion by removing WBC) PRBC < 2 weeks old
- Leucodepletion would minimize non-haemolytic febrile reactions and alloimmunization by removing
white cells contaminating PRBC

β-Thalassaemia Intermedia
- Clinical diagnosis where patients present later with less severe anaemia at > 2 years of age
usually with Hb 8g/dl or more
- Severity varies from being symptomatic at presentation to being asymptomatic until later
adult life. If they require regular transfusion, follow β-Thal major transfusion regime
α-Thalassaemia (Hb H disease)
- Transfuse only if Hb persistently < 7g/dl or symptomatic
When Hb is kept in normal range by blood transfusion, there is neither bone expansion nor anaemia or
extra iron absorption, the only problem is iron overload. As child grows, more blood & shorter interval
should be given. High transfusion starts with 30% more than low transfusion, in which patient have to
increase amount of blood later due to marrow expension & hypersplenism.
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Expected Hb rise with Hct levels:

Senario 1: Patient 20kg, 360mls transfusion every 4 weeks, average Hct 60%
1) Annual blood requirement = 13 transfusion x 360ml/20kg = 234 ml/kg/year
2) Annual pure RBC requirement = 234 x 60% = 140.4 ml/kg/year
3) Annual transfusional iron loading = 140.4 x 1.08 = 152 mg/kg iron
* Usual Hct level of Malaysian packed red cell ranges from 50-75%

Complications from transfusion:


Iron deposition - Cardiac siderosis (cardiomyopathy)
- Liver (cirrhosis)
- Pancreas (DM)
- Endocrine glands (eg. hemosiderosis in pituitary gland causing infertility)
- Skin (hyperpigmentation)
Antibody formation - Red cell antibodies
- HLA antibodies
- Ulticaria or anaphylactic shock
Infections - Hepatitis B & C, HIV, CMV, Syphilis, Malaria
Others (complications - Fluid overload
from massive BT) - Hypothermia
- Thrombocytopenia (leads to bleeding)
- Electrolytes imbalances (eg. hypernatremia, hyperkalemia)
- Citrate toxicity (leads to hypocalcemia)
- Febrile reaction (mild pyrexia is not a CI for BT)
- Acute respiratory distress syndrome (ARDS)

Formula for target volume of transfusion:


Target volume = (Post-Hb - Pre-Hb) x Weight x 4.5

Summary (Blood transfusion therapy)


- Transfusion should be initiated when patient is confirmed to have Thal major and Hb<7 g/dL, more than 2
weeks apart
- In Thal intermedia, consider transution when patient has FTT or bony deformities or extramedullary masses
- All patients should have full RBC phenotyping consisting of ABO, Rh, Kell, Kidd, Duffy & MNSs prior to first
transfusion
- All patients should also be tested for viral markers at diagnosis & every 6 months
(HbsAg, Anti-HCV, Anti-HIV antibody)
- Pre-transfusion Hb should be kept between 9.5-11.5 g/dL
- Post transfusion Hb should be between 13.5-15.5 g/dL
- Fresh blood <14 days and leucodepleted blood are advisable
- Volume of transfusion: 15-20 ml/kg, 2-4 weeks apart (depedent on Hct blood pack, preferably whole pack
blood should be utilised.
- In the presence of hypersplenism, consider splenectomy

275
2) Iron Chelation Therapy
- In most normal adults there are ~4g of iron in the body (3 g in RBC; 1g in liver storage). GIT
absorbs only ~10% in total daily diet; there is no natural way of getting rid of iron once it is in
the body, but a small amount excreted every day via skin & gut.
- This is essential to prevent iron overload in transfusion dependent thalassaemia.
- Compliance to optimal treatment is directly related to superior survival outcome, now possible
beyond the 6th decade.
- Currently 3 approved iron chelators are available:
- Desferrioxamine (DFO) - subcutaneous
- Deferiprone (DFP) - oral
- Deferasirox (DFX) - oral

i) Desferrioxamine (Desferal®)
MOA:
- It picks up iron from cells & brings it out in urine & stool & prevents the iron that is stored in
body from interfering with its normal function
- Serum ferritin level is best guide for whether the treatment is working or not
When to start?
- Usually when the child is >2-3 years old when serum ferritin reaches 1000 µg/L
- This usually occurs after 10-20 blood transfusions (250 mL pack rbc/ 1 unit of blood = contain
0.2g iron)
- In early stage, extra iron is stored in the liver (max 20g), when the storage is full, then iron is
accumulated in other organs, damaging the organs.
* Normal serum ferritin level = 100-400 μg/L
Dosage and route:
- Average daily dose is 20-40mg/kg/day, by subcutaneous (sc) continuous infusion using a
portable pump over 8-10 hours daily, 5 - 7 nights a week
- Aim to maintain serum ferritin level below 1000 μg/L
- Vitamin C augments iron excretion with Desferal
- Severely iron loaded patients require longer or continuous SC or IV infusion (via Portacath)
Complications of Desferal:
Local skin reactions - Usually due to inadequately diluted Desferal or infection
- Redness, swelling, hard tender lump
Yersinia infection - Present with fever, abdominal pain & diarrhea
- Stop desferal and treat with cotrimoxazole
Severe allergy - Rare
Desferal toxicity - High doses >50 mg/kg/day in the presence of low serum ferritin in
children
Ocular toxicity - Reduced vision, visual field and night blindness
- Reversible when Desferal is discontinued
Auditory toxicity - High tone deafness, usually irreversible
Growth retardation - Vertebral growth retardation
Skeletal lesions - Pseudo rickets, metaphyseal changes

276
Complications of chronic iron overload in Thalassaemics over 10 years:
Endocrine - Growth retardation
- Impaired glucose tolerance (DM)
- Pubertal delay
- Hypothyroidism
- Hypoparathyroidism
Cardiac - Arrhythmias
- Pericarditis
- Cardiac failure
Hepatic - Liver cirrhosis (especially if with Hepatitis B/C infection)

ii) Deferiprone / L1 (Ferriprox®/Kelfer®)


- Alternative if iron chelation is ineffective or inadequate despite optimal Desferal use, or if
Desferal use is contraindicated
- However, there is no formal evaluation in children <10 years of age
- Deferiprone is given 75-100 mg/kg/day in 3 divided doses
- Can abe used in combination with Desferal, using a lower dose of 50mg/kg/day
- There are risks of GI disturbance, arthritis and rare occurrence of idiopathic agranulocytosis
- Weekly full blood count monitoring is recommended. Stop if neutropenic (<1,500/mm3)
iii) Deferasirox (Exjade®)
- Can also be used for transfusional iron overload in patients 2 years or older but expensive
- Dose is 20-30 mg/kg/day in liquid dispersible tablet, taken once daily
- There are risks of transient skin rash, GI disturbance and a reversible ↑ serum creatinine
- Monthly monitoring of renal function is required

Degree of iron overload:


Mild Moderate Severe
Serum ferritin (µg/L) <2500 2500-5000 >5000
LIC (mg Fe/g DW) <7 7-15 >15
Cardiac T2 MRI (ms) >20 10-20 <10
* Cardiac T2 MRI is indicated for those >10 years old

Summary (Algorithm for Iron Chelation Therapy)


- Start chelation therapy if serum ferritin >1000 µg/L, usually at age 2-3 years
- First line is monotherapy DFO 20-40 mg/kg/day (children) up to 50-60 mg/kg/day (adults) s/c slow infusion 5
nights per week
- If inadequate chelation with DFO, consider:
- DFX 20-30 mg/kg/day in young children >2 years old OR
- DFP 75-100 mg/kg/day if >6 years old
- In mild iron overload:
- Continue current iron chelator
- Aim for serum ferritin <1000 µg/L
- In moderate to severe iron overload:
- Check compliance, optimise dose of current drug or monotherapy
- Switch to alternatives:
- Another monotherapy
- Consider DFP-DFO combination’
- IV DFO

277
3) Monitoring of Patients
Monitoring Assessment & Investigations
Blood transfusion - Screening for HbsAg, Anti-HCV, Anti-HIV 6 monthly
- During each admission for blood transfusion, following should be done:
- Pre-transfusion Hb, platelet count and WBC (if on Deferiprone).
- Post transfusion Hb-1⁄2 hour post transfusion.
- Calculate the volume of pure RBC transfused based on the haematocrit
(HCT) of PRBC given (usually HCT of PRBC from blood bank is >50-55%)
- Volume of pure RBC transfused = volume of blood given x HCT of PRBC
given (eg. 600 mls x 0.55 = 330 mls)
- Annual volume of pure RBC transfused per kg body weight
- Iron balance assessment.
Growth - Weight, Height & physical examination (liver, spleen size) 3-6 monthly
Medication - Review of current medications
Iron overload - Serum ferritin 3 monthly
Cardiac assessment - Annual ECG or Holter monitoring for arrhythmias
(>10 years old) - Annual cardiac echocardiography
- Cardiac T2* MRI (1-2 yearly)
- LIC MRI 102 yearly
Drug toxicity
- Desferrioxamine - Auditory/ ophthalmology annually
- Deferiprone - FBC weekly, ALT 3 monthly
- Deferasirox - RP, urine protein monthly, ALT monthly, Auditory/opthalmo annually
Growth failure - Test for DM, hypothyroidism, delyed puberty, zinc deficiency, bone
(Evaluate growth & disorders, DFO toxicity
development) - Bone age assessment
- GH stimulation tests (in referral centre)
Delayed puberty, short - Tanner staging 6 monthly
stature & hypogonadim - LH, FSH, oestradiol or testosterone
- Pelvic USS (for girls)
- GnRH stimulation test if necessary
Hypothyroidism - Free T4 and TSH
DM - Fasting plasma glucose or OGTT
Liver iron assessment - Liver T2* MRI for non-invasive assessment of liver iron
- Liver biopsy for liver iron concentration and the assessment of hepatitis,
fibrosis or cirrhosis in selected cases and prior to bone marrow
transplantation
Osteoporosis/osteopenia - Serum calcium, phosphate, ALP
- 25-OH VitD
- Serum zinc
- Spinal radiograph (AP & lateral view)
- DEXA scan
Hypoparathyroidism - Serum calcium, phosphate, ALP
- Serum magnesium
- PTH
Hypoadrenalism - Baseline cortisol at 8-9am
- ACTH stimulation test

278
4) Splenectomy
- Indications:
- Blood consumption volume of pure RBC > 1.5X normal or >200-220 mls/kg/year in those
>5 years of age to maintain average haemoglobin levels
- Evidence of hypersplenism
- Massive splenomegaly (risk of splenic rupture)
- Give pneumococcal and HiB vaccinations* 4-6 weeks prior to splenectomy
- Meningococcal vaccine required in endemic areas
- Penicillin prophylaxis for life after splenectomy.
- Low dose aspirin (75 mg daily) if thrombocytosis >800,000/mm3 after splenectomy (platelets
in blood usually high after splenectomy)
- Thromboembolic phenomenon is more common in patients with Thal intermedia, thus short-
term anti-thrombotic prophylaxis should be considered during risk periods
* Revaccination of HiB may be required after 5 years

5) Diet & Supplement


- Oral folate at minimum 1 mg daily may benefit most patients
- Low dose Vitamin C at 3 mg/kg augments iron excretion for those on Desferral only
- Dose: <10 yrs, 50mg daily; >10yrs, 100mg daily given only on deferral days
- Vitamin E supplmentation to reduce platelet hyperactivity & reduce oxidative stress
- Avoid iron rich food such as red meat and iron fortified cereals or milk
- Tea may help decrease intestinal iron absorption
- Dairy products are recommended as they are rich in calcium
- Calcium and zinc

6) Bone Marrow Transplantation (BMT)


- Potential curative option when there is an HLA-compatible sibling donor
- Results from matched unrelated donor or unrelated cord blood transplant are still inferior with
higher morbidity, mortality and rejection rates.
- Classification of patients into Pesaro risk groups based on the presence of 3 risk factors:
- Hepatomegaly > 2cm
- Irregular or inadequate iron chelation therapy
- Presence of liver fibrosis
- Class I patients have none of the above characteristics, patients in Class II have one or two,
while patients in Class III exhibit all three characteristics
- Best results if performed at the earliest age possible in Class 1 patients
- In newly diagnosed transfusion dependent thalassaemics, the family should be informed of
this option and referred early to a Paediatrician for counselling and HLA typing of patient and
unaffected siblings to identify a potential donor.
Pesaro Risk Groups and Outcome following BMT
Class No. of risk factors Event Free Survival % Mortality % Rejection %
1 0 91 7 2
2 1-2 83 13 3
3 3 58 21 28
Adults - 62 34 -

7) Antenatal diagnosis
- Can be done by chorionic villous sampling at 9-11 weeks period of gestation.
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8) Patient and parents support groups
- Various states and local Thalassaemia Societies are available nationwide
- Provide support and education for families
- Organises fund raising activities and awareness campaigns
- Health professionals are welcomed to participate.

B) α-Thalassaemia

Epidemiology:
- Common in Asian population
Pathology:
- There are 4 α-globin genes coded by chromosome 16
- Reduced synthesis of α globin chains of Human Hb
- Clinical manifestations depend on the number of functional genes
Types of α-Thal:
Thal minor - α-thal 1-2 α globin genes deleted
(trait/carrier) - α-thal 2-1 α globin genes deleted
- Asymptomatic/ incidental finding
- Absent OR mild hypochromic microcytic anemia

Thal - Deletion of 3 α-globin genes (tetramers of β chains; β4)


intermedia - 1 functional α globin gene
(HbH - Moderate chronic hemolytic anemia (7-10 g/dL)
disease) - Normal life expectancy & blood transfusion may be required during fulminant
infection, pregnancy and uses of oxidant drugs
- ~30% have mongoloid facies, ~70% have hepatosplenomegaly
- Can be diagnosed at birth: presence of Hb bart 20-40% in cord blood

Hb Bart - Deletion of all 4 α-globin genes (tetramers of fetal γ-chains; γ4)


- 0 functional α globin gene
- hydrops fetalis (incompatible with life due to ineffective O2 transport) & death in-utero
- Associated with eclampsia & obstructed labor to the mother
* Hb Bart (γ4)
- High oxygen affinity Hb
- No heme-heme interaction (no Bohr effect)
- Functionally useless Hb for oxygen transfer - severe hypoxia

Diagnostic criteria for α-Thalassaemia:


Types Clinical Diagnosis Laboratory Diagnosis
α-Thalassaemia trait - Normal to mild anaemia - Hb (>10 g/dL)
- No organomegaly - MCH (<27 pg)
- Hb analysis (normal)
- H inclusion may be present
- DNA studies may be necessary

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Thalassaemia Long Case (Template):
A. History
General profile
(Age, Gender, Ethnicity - HbE more likely in Malays & Chinese)
Presenting complaints (Reason for admission, consider)
- Visit to drug therapy centre for regular blood transfusion
- Admission for elective surgery (eg. splenectomy, cholecystectomy)
- Symptoms of complications (cardiomyopathy, CCF, DM, worsening anaemia, jaundice)
- May also be causes not directly related to thalassaemia
HOPI - Bring past-medical history of Thalassaemia under this section (unless presenting complaint not
related to Thalssaemia)
Diagnosis of - Age of diagnosis (antenatal/infantile/childhood)
Thalassaemia - Initial presentation (increasing pallor, FTT, jaundice, ↓ET, LOA, syncope)
- Where it was diagnosed, investigations done
- Ellicit most probable type of Thalassaemia
- β-Thal major (6-12 months)
- β-Thal intermedia/HbE (late >2 years old)
Treatment History
- Ask about age of first transfusion
- Age when chelation therapy started
- How often are transfusion needed per year (Quantify)
- Other medications (eg. Folate, VitC, B-complex, Thyroxine-short stature, Penicillin-post-splenectomy)
- Drug allergy
- Hospitalisations (other than PCT) & reasons
- Previous surgery (eg. splenectomy, cholecystectomy)
A) Blood transfusion - Blood group
- Frequency & volume (pints)
`Hb from previous transfusion range from __ to __`
- Pre & Post-transfusion Hb (maintain adequare transfusion to prevent
extramedullary erythropoiesis)
- Pre-transfusion: 9.5-11.5 g/dL
- Post-transfusion: 13.5-15.5 g/dL
`My patient was active before & after transfusion, no complications noted`
- When started? Why? When Hb <8g/dL for 2 weeks? Severe anaemia?
- Infective screening (HepB,C,HIV) every 6 months until now (-ve/+ve)
- Current serum ferritin level (normal 100-400 ng/ml)
- Control:
- Symptoms & progression of anaemia few weeks before transfusion?
- Need for any unscheduled transfusion?
- Is growth appropriate to chart?
- Symptoms of extramedullary erythropoiesis? Increasing size of mass in
abdomen?
- Complications from blood transfusion:
- Mild: Rash, itchy, ulticaria (Tx: hydrocortisone)
- Severe: Hypotension, anaphylactic shock, bronchospasm
- Complications from iron overload:
- Cardiac siderosis (CCF, cardiomyopathy) – echo yearly
- Endocrine
- Pancreas (DM) - HOPI can be elective admission for insulin therapy
- Hypogonadism (amenorrhoea,↓pubertal staging, absence pubic hair)
- Hypothyroidism (less active)

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- Short stature (GH insufficiency)
- Osteoporosis
- Liver (chronic liver disease)
B) Iron chelation cherapy - Started when serum ferritin level >1000 ng/ml after __ no. of transfusion
- Types: Desferal, Deferiprone (>5 years old), Deferasirox (2-3 years old)
- On monotherapy? If desferal, who inject the drug? Use of infusion pump?
- After chelation, target ferritin level achieved? Below 1000ng/ml?
- Vit C given? Dosage? To augment iron excretion from stool
- Compliance:
- How many bottle of infusion needed?
- Any missed day in a week/month?
- Calculate percentage of compliance per month: x/30 x 100%
- For Desferal, 20-60mg/kg/day (max 50), 8-10 hours daily, 5-7 nights/week
- Complications:
- Local skin infections (redness, swelling, pain)
- Yersinia infection (abdominal pain, fever, diarrhoea) - on antibiotics?
- Severe allergy
- Desferal toxicity (>50mg/kg/day)
- Ocular toxicity (reduced vision, night blindness)
- Auditory toxicity (high tone deafness)
- Growth retardation
- Skeletal lesions (pseudorickets, metaphyseal changes, fracture)
C) Splenectomy - When was started? >5 years old
- Why?
- Hypersplenism (pancytopenia with pooling of blood)
- ↑ splenomegaly (risk of rupture when spleen fails)
- Pre-vaccination (>2 weeks; 4-6) before surgery
- Meningococcal, Pneumococcal, Hib (If given <5 yrs old ↑ infection risk)
- Post-surgery
- Lifelong penicillin (↓streptococcal infection)
- Low dose aspirin (antiplatelet): prevent thrombosis (thrombocytosis
after splenectomy)
- Complications:
- Requires ICU monitoring (infections), discharge after how many day?
Past-Medical & Surgical History
Past-Medical - Other than associated conditions of thalassaemia
Past-Surgical - Splenectomy
Drug History
Drugs - Any supplementation (folic acid?)
- Drug allergy
Family History
Parent - Parent genetic status, do they know they are carriers? Consanguinity?
- Genetic counseling done before?
- Draw family tree
Siblings - Any affected? If yes, on any treatment? Severity?
- If not affected, possibility of stem cell transplant?
Paediatrics History
Birth history - Neonatal anaemia? IUGR? G6PD deficiency?
Immunisation history - Completed immunisation?
Developmental history - Any developmental delay?
- Abnormal pubertal staging
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Dietary - Any restricted diet (less intake of iron, red meat, peanut butter, curry
powder, use of iron pan)
- Food allergy
Social History
Disease impact on the - Schooling (which stream, level), Academic performance (rank, best
child subject), Amount of school missed, Behaviour, conduct, Able to take part
in physical class/sports?
- Body image, pubertal anxieties (in teens)
- Psychosocial (depression, low self-esteem & relationship)
Disease impact on the - Occupation of caretakers
family - Financial considerations (cost of Desferal+pump) expensive
- Social support group available

Understanding of disease - Perception of disease


- Compliance with medications

Summary
In summary, my patient is a (age/race/gender) who has (β-Thal major/HbE β-Thal/HbH), who is
- Transfusion-dependent
- Clinically thalassaemia major/intermedia
- Ongoing problems/issues include _____ & reason for hospitalisation is ______.
- Complications (without evidence of iron overload)
B. Physical Examination
General inspection:
- Bronze-skin
- Short stature
- Attached PCT, oxygen, IV lines (infusion of medication)
- Thalassaemic facies (frontal bossing, maxillary overgrowth, malar eminence)
- Pallor (conjunctival, nailbed, palmar crease)
- Jaundice (scleral jaundice, generally appear jaundice)
Abdomen:
- Desferal scars (pigmented, round, no lipodystrophy)
- Surgical scars (open/laparoscopy)
- Hepatomegaly +/- Splenomegaly
Chest:
- Apex beat displaced?
- Flow murmur?
- Signs of CCF?
Others:
- Signs of CLD
- Signs of hypothyroidism (dry,scaly hair, hyporeflexia etc)
- Screen visual acuity
- Tanner staging (if parent allows)
C. Discussion
- Refer previous pages for detailed investigation and management in Thalassaemia.
- Mainstay of management should include blood transfusion, iron chelation therapy, splenectomy (if
hypersplenism), genetic counseling & screening, dietary advices and management for complications.
Bone marrow transplant should depend on patient`s siblings.

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Haemostasis

- Processs of haemostasis involve vasculature, platelets and coagulation factors.

Clinical features:
History Most likely aetiology
(overlap considerable)
- Easy bruising (ecchymoses) Coagulation defects, platelet or
vascular
- Petechiae (skin & mucous membranes)
- Mucosal bleeding:
- Gum bleeding
- Epistaxis Platelet disorders
- Haematuria
- Menorrhagia
- Internal bleeding (GIT, intracranial, intramuscular)
- Bleeding into joints (haemarthroses) with minor injuries
- Bleeding into muscles Coagulation defects
- Excessive bleeding after trauma (eg. surgery, dental
extractions)
Examination
- Skin (Petechiae: ~1-2mm spots; Purpura: <1cm, varying shape & Ecchymoses: >1cm, varying shape)
- Mucous membrane (Palatal petechiae, gum bleeding)
- Assymetrical joint deformities (due to haemarthroses)

Normal Coagulation Cascade:

APTT
(Heparin)

PT/INR
(Warfarin,
liver damage)

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Investigation of clotting disorders:
Test Mechanism Abnormal in DIC
FBC & PBF Platelet morphology & count
Bleeding time Abnormalities of other blood cells, Prolonged in
measures platelet plug formation in vitro thrombocytopenia, platelet
function disorders & von
Willebrand disease
Prothrombin time (PT) Measures factors VII, X, V, prothrombin & Prolonged in liver disease,
fibronogen (extrinsic & common vitamin K dependent clotting
pathyways) (INR=1) factors; Used to monitor
Normal=10-14s warfarin therapy
Activated partial Measure factos V, VIII, IX, X, XI, XII, Used to monitor heparin
thromboplastin time prothrombin & fibrinogen (intrinsic & therapy
(APTT) common pathways)
Normal=30-40s
Thrombin clotting time Normal=14-16s Abnormal in fibrinogen
(TT) deficiency or thrombin
inhibition
Coagulation factors Specific assays of individual clotting Clotting factor deficiencies (eg.
factors haemophilia)
Abnormal in DIC
Fibrinolysis tests Detection of fibrinogen or fribrin Decrease in enhanced
degradation products (FDPs), fibrinolysis
Plasminogen & plasminogen activator
raised

A) Disorders of Vasculature
- Clinical features are generally mild, with skin & mucous membrane bleeding (bruising,
petechiae). All screening tests are normal including the bleeding time.
- Aetiology:
Inherited - Ehlers-Danlos syndrome
- Hereditary haemorrhagic telangectasia
- Marfan`s syndrome
Acquired - Easy bruising syndrome
- Vasculitis (eg. Henoch-Schonlein purpura (HSP))
- Infection (eg. meningitis)
- Vitamin C deficiency (scurvy)
- Drugs (eg. steroids)

B) Platelet disorders
- Include thrombocytopenia & platelet dysfunction
1) Thrombocytopenia (when platelet count <150 x 109/L)
Classification Platelet count x 109/L Risk
Severe <20 Risk of spontaneous bleed
Moderate 20-50 Risk of excess bleed during operation or trauma
Low risk of spontaneous bleed
Mild 50-150 Low risk of bleed during operation or trauma
- Clinical features: Bruising, Petechiae/ecchymoses, Purpura, Mucosal bleeding (epistaxis, gum),
GIT bleeding, Haematuria, Intracranial haemorrhage)
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- Aetiology:
1) Increased platelet consumption/destruction
Immune - ITP
- SLE
- Alloimmune neonatal thrombocytopenia
Non-immune - Haemolytic Uraemic Syndrome (HUS)
- Thrombotic Thrombocytopenic Purpura (TTP)
- DIVC
- Congenital heart disease
- Giant haemangioma (Kasabach-Merritt syndrome)
- Hypersplenism (liver disease, haemolytic disease)
2) Decreased platelet production
Congenital - Fanconi`s anaemia
- Wiskott-Aldrich syndrome
- Bernard-Soulier syndrome
- Thrombocytopenia with absent radius (TAR syndrome)
Acquired - Aplastic anaemia (cytotoxic drugs)
- Leukaemia, Lymphoma
- Dengue, HIV
- Drug-induced (penicillin, heparin)
- Radiation

2) Platelet Dysfunction
- Platelet count is normal but bleeding time is prolonged & specific platelet function tests are
abnormal. They may be inherited or acquired.
- Aetiology:
Congenital - Glanzmann`s thromboasthenia (rare)
Acquired - Drugs
- Aspirin (Inhibition of cyclo-oxygenase)
- Heparin (Platelet segregation & secretion inhibited)
- Myeloproliferative disease
- Uraemia

C) Clotting factor disorders


- X-linked recessive inheritance, 30% there is no family history (spontaneous new mutation)
- A group of blood disorders in which there is a defect in clotting mechanism
- Most common: Haemophilia A (Factor VIII deficiency), Haemophilia B (Factor IX deficiency)
- Clinical features: Bleeding during neonatal period (unusual), usually presents with easy
bruising when crawling & walking (9-12 mths), Haemarthrosis (large joints: knee,ankle,elbow),
Epistaxis, gum bleeding, haematuria, intracranial haemorrhage, recurrent spontaneous
bleeding into joints & muscles (crippling arthritis), bleeding post-circumcision
- Investigations:
- FBC
- Coagulation screen (PT, APTT)
- Specific factor assay (FVIII-low in Haemophilia A, FIX-low in Haemophilia B)
- Bleeding time is applicable
- vWF screen even if APTT normal

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- In haemophilia, APTT is prolonged in moderate and severe haemophilia but may not show
prolongation in mild haemophilia. PLT & PT are normal. When APTT is prolonged, proceed to do
FVIII antigen level. If this is normal, only then proceed to assay the Factor IX level. Once the level
has been measured, then the haemophilia can be classified as below.
Classification of haemophilia and clinical presentation
Factor level Classification Clinical presentation
<1 % Severe Spontaneous bleeding, risk of intracranial haemorrhage
1-5 % Moderate Bleeding may only occur with trauma, surgery or dental
5-25 % Mild procedures

- Further Investigations
- HbsAg, anti-HBS, anti-HCV, HIV serology
- RP, LFT, Platelet aggregation (if high suspicion of platelet defect)
- Diagnosis of carrier status for genetic counseling
- Mother of a newly diagnosed son with haemophilia
- Female siblings of boys with haemophilia
- Daughter of a man with haemophilia
- Once a child is diagnosed to have haemophilia, check the viral status at diagnosis & then
yearly. This is because treatment carries the risk of acquiring viruses. All haemophiliacs should
be immunized against Hepatitis B.

- Treatment
- Treatment of severe haemophilia should be prophylactic to prevent arthropathy & ensure
best quality of life possible. Dosage of prophylaxis is usually 25-35 U/kg of FVIII concentrate,
given every other day or 3x/week. For FIX, the dosage is 40-60 U/kg, given every 2-3 days.
However, this form of management is costly & requires central venous access.
- On demand treatment is another option for inadequate clotting factors are. It consists of
replacing the missing factor: FVIII con-centrates (Haemophilia A), FIX concentrates
(Haemophilia B). FFP & cryoprecipitate ideally SHOULD NOT be used (high risk of viral
transmission). Dose of factor replacement depends on the type & severity of bleed.
- Dose of factor required can also be calculated using the formulas below
- Units of FVIII: (% rise required) x (weight in kg) x 0.5
- Units of FIX: (% rise required) x (weight in kg) x 1.4
- Percentage of factor aimed for depends on the type of bleed
- For haemarthroses, 30-40 % is adequate
- For soft tissue or muscle bleed aim for 40- 50 % level.
(there is potential to track and cause compression/compartment syndrome)
- For intracranial bleeds or patients going for surgery, aim for 100%
- Infuse FVIII by slow IV push at a rate not exceeding 100 units/min in young children
- FVIII is given every 8-12 hours. Factor IX is given every 12 - 24 hours.
- Duration of treatment depends on type of bleed:
- Haemarthroses 2-3 days
- Soft tissue bleeds 4-5 days
- Intracranial bleeds or surgery 7-10 days.
- Veins must be handled with care. Never perform cut-down unless in an emergency
as it destroys the vein.

287
- Complications:
- Joint destruction
Recurrent haemarthroses into same joint will destroy the joint causing osteoarthritis &
deformity, this can be prevented by prompt & adequate factor replacement
- Acquisition of viruses (Hepatitis B, C or HIV)
Immunisation and regular screening recommended.
- Inhibitors:
These are antibodies directed against the exogenous factor VIII or IX neutralizing the clotting
activity. Can develop at any age but usually after 10-20 exposure days. Suspected when there
is lack of response to replacement therapy despite high doses. Treatment requires `bypassing`
the deficient clotting factor. Currently 2 agents are available - Recombinant activated FVII
(rfVIIa or Novoseven) & FEIBA. Immune tolerance induction is also another option.

Haemophilia A & B:

D) von Willebrand disease (vWD)


- AD, worse in female (menstruation
- vWF (carrier protein for FVIII & promotes platelet adhesion), deficiency causes low FVIII activity
& platelet adhesion abnormalities
- Clinical features:
- Excessive traumatic bleeding (from cuts & operative and mucous membranes-epistaxis, gums,
menorrhagia)
- Spontaneous bleeding (rare except in homozygous)-haemarthroses & muscle bleeds
- Investigation:
- Prolonged bleeding time (platelet adhesion decreased)
- FVIII activity reduced
- vWF levels reduced
- Platelet aggregation with reduced ristocetin activity

288
- Management:
- FVIII concentrate infusions containing vWF (severe)
- DDAVP & fibrinogen inhibitors (milder)

E) Disseminated Intravascular Coagulation (DIC)


- State of consumption of platelets & clotting factors with widespread intravascular fibrin
deposition dt uncontrolled activation of clotting cascade. It can be acute or chronic (mild, rarer)
- Clinical features: Severely unwell with generalised bleeding, petechiae & bruising (acute form)
- Investigation: FBC, PBF (thrombocytopenia, microangiopathic anaemia); TT↑, APTT↑, PT↑,
FDP↑, Fibrinogen↓, FV↓, FVIII↓

- Management:
- Treat underlying cause
- Supportive therapy on ICU (blood, FFP, fibrinogen, PLTs)
- Protein C concentrates given in meningococcal sepsis DIC

Haemostasis Test:

Congenital Prothrombotic Conditions:


Factor V Leiden deficiency Abnormal Factor V (1% Causasian population)
Protein C deficiency Protein C inactivates FV, VIII and stimulates fibrinolysis
Protein S, Antithrombin III deficiency Cofactor for Protein C, Inhibition of thrombin & Factor X

289
Autoimmune Thrombocytopenic Purpura (AITP)

Definition: (aka Idiopathic Thrombocytopenic Purpura)


- Isolated thrombocytopenia with otherwise normal blood count in a patient with no clinically
apparent associated conditions that can cause thrombocytopenia (such as HIV infection, SLE,
lymphoproliferative disorders, alloimmune thrombocytopenia and congenital or hereditary
thrombocytopenia).

Epidemiology:
- Commonest cause of thrombocytopenia in childhood
- Usually affects children aged 2-10 years old

Aetiology:
Acute AITP Chronic AITP
- Post viral infection - Usually idiopathic
- Usually presents after 1-2 weeks after a - Associated with autoimmune disorders
viral infection - SLE
- Thyroid disease
- Chronic lymphatic leukemia
- Viral infections (e.g. HIV)
- Drugs (e.g. that cause AHA)
*AHA = autoimmune haemolytic anaemia (e.g. quinine, penicillin, methyldopa)

Pathogenesis:
- Thrombocytopenia results from an immune-mediated destruction of circulating platelets (due
to anti-platelet autoantibody) within the reticuloendothelial system (especially spleen)
- ↓platelet counts accompanied by a compensatory↑megakaryocytes (platelet precursors) in
bone marrow

Classification:
Acute AITP Chronic AITP
- 1 or 2 weeks of duration - >6 months duration
- Usually occurs in children - Usually occurs in adults/teenagers
- Male: Female = 1: 1 - Male: Female = 1: 3
- History of viral infection - Usually no history of viral infection
- Rapid onset of purpura - Associated with autoantibodies (60-70%)
- Self-limiting illness (95%) & only 5%
becomes chronic

Clinical features
Symptoms Signs
- History of fever (post viral infection) - Petechiae & purpura
- Bleeding tendencies, easy bruising - Superficial bruising (ecchymoses)
- Mucosal bleeding (e.g. gum bleeding) - No hepatosplenomegaly
- Epistaxis, PR bleed, haematemesis, - No lymphadenopathy
- Haematuria - Intracranial bleeding (rare; 0.1-0.5%)
- Menorrhagia (after puberty) - Positive tourniquet test (Hess test)
*Spontaneous bleeding usually occurs when platelet counts <20 x 109/L

290
Investigations:
- Diagnosis is principally based on on the history, physical examination, full blood count &
examination of peripheral smear
- Diagnosis by exclusion (should exclude other causes of thrombocytopenia)
Blood - FBC
- Normal Hb & WBC
- ONLY thrombocytopenia (<150 x 109/L or <100 x 109/L)
- But look for other associated blood parameters disorders (e.g. pancytopenia)
- FBP
-↓amount and ↑size of platelet
- Prolonged bleeding time (normal:≤11 mins, not practised nowadays)
Biopsy - Bone marrow aspiration (controversial)
- Threshold for performing a bone marrow aspiration must be low
- Indicated if there is:
- Presence of atypical features e.g. organomegaly, significant lymphadenopathy,
abnormal blood counts or suspicious peripheral blood picture
- Before starting steroid therapy (to avoid partially inducing an undiagnosed
acute leukemia)
- Not responding to IV Ig therapy
- Persistent thrombocytopenia beyond 6 months
- Thrombocytopenia recurs after initial respond to treatment
*Others tests maybe indicated when there is atypical presentation from the history, physical
examination, FBC or PBF (eg. Antinuclear factor, Coomb`s test, ultrasound of abdomen, HIV testing)

Management:
- Not all children with diagnosis of acute ITP need hospitalization (80% is acute, benign, self-
limiting)
- Hospitalization is indicated if:
- Severe life-threatening bleeding (e.g. ICH) regardless of platelet count
- Platelet count <20,000 with evidence of bleeding
- Platelet count <20.000 without bleeding but inaccessible to health care
- Parents request for admission
- Most of childhood ITP remit spontaneously with 70% achieves platelet count >50,000 by the
end of 3rd week
- Careful observation and monitoring platelet count without specific treatment is appropriate for
patients with
- Platelet count >20,000 without bleeding
- Platelet count >30,000 with only cutaneous purpura
- Treatment is indicated if there is:
- Life threatening bleeding episode (e.g. ICH) regardless of platelet count
- Platelet count <20,000 with mucosal bleeding
- Platelet count <10,000 with any bleeding
- Choice of treatment
- Oral prednisolone 4mg/kg/day for 7 days, then taper and discontinue at 21 days
- IV Methylprednisolone 30mg/kg/day for 3 days
- IV Immunoglobulin 0.8g/kg/dose for 1 day or 250mg/kg for 2 days
- IV Anti-Rh(D) Ig (50-75mg/kg) in Rhesus positive patients → may cause haemolytic anemia
- All are effective in raising platelet count quicker compared to no treatment with IVIG quickest
291
- However no direct evidence indicates that any of these treatments reduce bleeding
complications or mortality from ITP. No influence on progression to chronic ITP.
- Side effects of IVIG is common (15-75% incidence) and include fever, flushing, headache,
nausea, aseptic meningitis and transmission of Hepatic C (older preparation).
- Steroids should not be continued, however, if there is no response or if there is a rapid relapse
after withdrawal. The considerable risks of long term side effects in a growing child outweigh
benefits of either too frequent high dose pulses or any attempt to titrate the platelet count
against a regular lower steroid dose.
- Platelet transfusion are reserved for life threatening haemorrhage (↑platelet only for few
hours)
- Treatment should not be directed at increasing platelet count above a preset level but rather
on the clinical status of the patient.

Chronic ITP
- Persistent thrombocytopenia after 6 months of onset (20%)
- Wide spectrum of manifestations varying from mild symptomless low platelet counts through
intermittent relapsing symptomatic thrombocytopenia to the rare stubborn and persistent
symptomatic and haemorrhagic disease
- Management
- Every opportunity should be given for disease to remit spontaneously as the majority will do
so if given enough time
- Revisit the diagnosis to exclude other causes of thrombocytopenia (Immunodeficiency,
lymphoproliferative or collagen disorders or HIV infection).
- Asymptomatic children can be left without therapy and kept under observation.
- Symptomatic children may need short course of treatment to tide them over the relapse
which include:
- Intermittent pulses of IVIg
- Intermittent anti-Rh(D) antibody treatment for those with Rhesus D positive
- Intermittent pulses of steroid
- Care must be taken with any pulse of steroid strategy to avoid treatment-related steroid side
effects. Aware of immunosuppression eg. risk of severe varicella
- No justification for long term continuous steroids
- Splenectomy is indicated when:
- Persistence of disease after 12 months with
- Bleeding symptoms and
- Platelet count <10,000/µL to 30,000/µL (ages 8-12 years)
- No response or only transient success with intermittent IVIg, anti-D or pulse steroids
- No contra-indications to surgery. Operative mortality <1%
- Over 70% rate of complete remission post splenectomy
- Pre-splenectomy immunization against pneumococci, haemophilus influenza type b and
meningococci infection mandatory 2 weeks before surgery
- Post-splenectomy penicillin prophylaxis
- Post-splenectomy failure or relapse, consider: danazol, vincristine, azathioprine,
cyclophosphamide, alpha-interferon, stahphylococcal protein A immunoadsorption,
cyclosporine, cholchicine or dapsone.

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Henoch-Scholein Purpura (HSP)

Definition: (aka anaphylactoid purpura)


- Small vessel vasculitis, combination of triads:
- Characteristics, skin rash (purpura)
- Arthralgia & periarticular edema
- Abdominal pain or glomerulonephritis

Epidemiology:
- Usually occurs at age between 3-10 years old
- Twice as common in boys
- Peak during the winter months
Pathophysiology:
- Aetiology of HSP is unknown.
- Postulations:
Genetic predisposition & Antigen exposure
- Increase circulating IgA levels and disruption
in IgG synthesis
- IgA & IgG interact to produce complexes that
activate complement
- Deposited in affected organ
- Precipitate inflammatory response with vasculitis
*HSP and IgA nephropathy are related disorders. Both illnesses have elevated serum IgA levels and
identical findings on renal biopsy

Clinical Features:
Symptoms Signs
- Preceded by URTI - Characteristic rash (1 clinical features in
st

- Fever 50% of patients)


- Arthralgia (2/3 of patients) - Symmetrically distributed over
- Knees & ankles (non-destructive arthritis) - Buttocks, pressure points, sock line
- Colicky abdominal pain - Extensor surfaces of arms, legs & ankles
- If severe, give corticosteroids - Trunk spared; unless induced by trauma
- Hematemesis & melena - Initially urticarial → maculopapular →
- If gastrointestinal petechiae develops purpura (palpable)
- Renal involvement (80%) - Glomerulonephritis - Periarticular edema
- Hematuria (micro or macroscopic) - No damage to the joints
- Mild proteinuria
- Subcutaneous edema & scrotal edema

Complications:
Abdomen Others
- Intussusception (intramural haematoma) - Hypertension
- Ileus - CNS involvement
- Protein-losing enteropathy
- Nephrotic/nephritis syndrome
- Deteriorating renal function
- Orchitis

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Diagnosis:
- Clinical diagnosis and not based on laboratory evaluation

Investigations:
- Routine laboratory test results are usually within reference ranges.
- Some laboratory studies TRO other diagnoses and in evaluating renal function
- Urinalysis: Hematuria/ proteinuria are present in 10-20% of patients
- Platelet count and coagulation studies:
- Platelet count is usually in the reference range but may be elevated; the platelet count
should not be low in HSP. A normal platelet count rules out idiopathic thrombocytopenic
purpura (ITP). A normal platelet count and normal coagulation studies (eg., PT, aPTT, FDP)
rule out thrombotic thrombocytopenic purpura (TTP).
- Lipase: A normal lipase level makes acute pancreatitis very unlikely.
- FBC and differential: WBC count may be in the reference range or elevated. Eosinophilia is
sometimes present.
- Erythrocyte sedimentation rate: Sedimentation rate may be in the reference range/ elevated.
- BUN and creatinine levels: May be elevated from renal involvement of HSP/ from dehydration.
- Abdominal ultrasound may be better than barium enema to diagnose intussusception.
- IgA level (elevated in >50%)

Management:
- Very limited data are available on the treatment of Henoch-Schonlein purpura. Fortunately,
most patients recover quickly in several weeks without treatment.
- Treat any suspected infection
- Supportive therapy for rash, arthalgia, fever & malaise
- For renal disease:
- Standard treatment of nephritic or nephrotic syndrome (see below)
- Renal biopsy (if severe hypertension or rising creatinine)
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Helps joint pain and do not seem to worsen the purpura. However, NSAIDs should be used
cautiously in patients with renal insufficiency. Clinicians often use corticosteroids to treat
abdominal pain, subcutaneous edema and nephritis, but few prospective placebo-controlled
studies have demonstrated their effectiveness.
- Prednisolone in a dose of 1 mg/kg/day for 2 weeks and then tapered over 2 more weeks
- Shown to improve gastrointestinal and joint symptoms. Although this regimen did not
decrease the incidence of renal disease, it did lessen the severity of nephritis in some patients.
Other treatment regimen have included IV or oral steroids with or without any of the
following: azathioprine, cyclophosphamide, cyclosporine, dipyridamole, plasmapheresis, high
dose IV immunoglobulin G (IVIg), danazol, or fish oil.

Prognosis:
- HSP is generally a benign disease with an excellent prognosis.
- More than 80% of patients have a single isolated episode lasting for a few weeks.
- Approximately 10-20% of patients have recurrences.
- Fewer than 5% of patients develop chronic HSP.
- Abdominal pain resolves spontaneously within 72 hours in most patients.

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Sickle Cell Anaemia
Introduction:
- AR, common sickle cell syndromes include HbSS, HbSC and HbS-β-thal, others are rare variants
- Hb phenotype must be identified as clinical complications differ in frequency, type and severity
- Sickle cell Hb (HbS) is Hbα2βs2, single amino acid substitution (valine for glutamic acid at
codon 6 on β-chain → HbS crystallise and form a gel in deoxygenated state → normally soluble
when reoxygenated (reversible HbS) and able to enter microcirculation
- HbS is insoluble in low oxygen tension → polymerises as long fibers (sickle-shaped) → block
microcirculation → microinfarction → pain and dysfunction
- HbS releases oxygen in tissure more readily than HbA (OxyHb dissociation curve shift to right)
- 2 common clinical conditions:
- Sickle cell anaemia HbSS (homozygous disease, 85-95% HbS, 5-15% HbF, no HbA)
- Sickle cell trait HbSA (carrier, heterozygous disease, 40% HbS, 60% HbA)

A) Sickle cell anaemia


- HbSS disease, seen in Africans, Mediterraneans & Indians
- Clinical features vary depending on any coexisting haemoglobinopathies, eg. HbS-β-thal is
mild while HbSS is worse
- Clinical features:
Acute Chronic
- Life-threatening infections (fever) and functional - Anaemia (Hb 6-9 g/dL, moderately severe,
asplenia (usually by 4 months of age) haemolytic, not routinely transfusion dependent)
- Pneumococcal bacteremia - Jaundice, Pallor
- Severe Mycoplasma pneumonia - Reticulocytosis (5-15%)
- Meningitis, deafness, arthritis - Failure to thrive (due to chronic disease)
- Pigment gallstones (due to haemolysis)
- Intermittent crises (Refer below) - Salmonella & Staphylococcus osteomyelitis
- Splenic sequestration crisis - Aseptic/Avascular necrosis
- Vaso-occlusive crisis - Priapism (blood pooling within the corpora
(Acute chest syndrome or Pain crisis) cavernosa, eventual impotence)
- Aplastic crisis - Dactylitis (6 months of age)
- Haemolytic crisis - Renal failure (haematuria, papillary necrosis,
renal concentrating defect)
Sickling phenomenon/crisis is exacerbated by:
- Congestive cardiac failure (cardiac flow murmur,
- Hypoxia
- Acidosis cardiomegaly)
- Fever (infection) - Chronic lung disease (pulmonary fibrosis,
- Hypothermia restrictive lung disease, cor pulmonale,
- Dehydration pulmonary hypertension)
- Proliferative retinopathy
- Splenomegaly (infancy)
- Stroke
- Autosplenectomy (due to splenic crises, usually
- Overt (8-10%, seizure, altered consciousness,
2-4 years of age)
focal paralysis)
- Leg ulceration (older patients)
- Silent (20%, significant change in school
- Psychological problems
performance or behaviour)
- Narcotic addiction (rare)
- Dependence (unsual)
- Chronic pain syndrome

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Sickling crises:
- Most episodes of crises last between 5-7 days
Splenic - Life-threatening, hyperacute ↓Hb 2` to splenic pooling of RBC and sickling
sequestration crisis within spleen (moderate to massive splenomegaly, RR↑), hypovolemic shock
- ↑infection risks from encapsulated organisms
- Transient, continue for 3-4 hours and may last for one day
- Management: Blood transfusion, Prophylactic antibiotics, Vaccination
Vaso-occlusive - Occurs in any organ with clinical symptoms of pain or organ dysfunction (due to
crisis restriction in blood flow → ischaemia → pain & necrosis)
- i) Acute chest syndrome
- Vaso-occlusive crisis within lungs with evidence of new infiltrate on CXR
- Defined by ≥2 of: chest pain, fever, CXR: pulmonary infiltrate/focal abnormality
- 2nd most common complication, 25% of death in sickle cell patients
- Associated with infection and infarction, atelectasis, fat embolism
- Initial complaint of chest pain, develops cough, ↑RR, ↑HR, hypoxia and
progressive respiratory distress in later stage
- PE: ↓breath sounds, dullness on percussion
- Management:
- Early recognition and prevention of arterial hypoxemia
- Oxygen, fluids, analgesics (use wisely), antibiotics, bronchodilators, RBC
transfusion (rarley exchange transfusion)
- Incentive spirometry may help ↓incidence of acute chest crisis presented with
chest or abdominal pain ↓ development of atelectasis
- ii) Pain crisis (most common type of vaso-occlusive event)
- Microvascular painful infarcts of muscle, bone, bone marrow, lung, intestines
- Usually localises to long bones of arms/legs but may occur in smaller bones of
hands or feet in infancy (dactylitis) or in abdomen
- Usually last 2-7 days
- Crises within femur → avascular necrosis of femoral head or chronic hip disease
- Management:
- Fluids, analgesics (usually narcotics & NSAIDS), oxygen if hypoxic
- Priapism can occur in boys (between 6-20 years old)
- Experiences sudden, painful onset of turnescent penis that will not relax
- Management: Administration of oxygen, fluids (due to renal medullary
infarction which results in loss of ability to concentrate urine), analgesia,
transfusion (achieve HbS <30%, often by partial exchange transfusion)
Aplastic crisis - Acute and reversible worsening of patient`s baseline anaemia
- Presented with pallor, tachycardia, fatigue
- Usually triggered by parvovirus B19 infection (invades RBC precursors,
multiplying and destroying RBC, almost complete cessation of RBC production
for 2-3 days)
- Reticulocytopenia, rapid RBC turnover (↓Hb)
- Management: Supportive, blood transfusion (sometimes)
Haemolysis crisis - Acute accelerated ↓Hb (RBC break down at faster rate)
- Common in patient with coexistent G6PD deficiency
- Management: Supportive, blood transfusion (sometimes)

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B) Sickle trait
- Heterozygote expression of sickle Hb gene eg. HbSA
- HbS makes up 30-40% of Hb, appears partially protect against falciparum malaria
- Usually asymptomatic with no anaemia
- Sickling can occur in severe hypoxia, haematuria is the commonest symptom
- Special care is needed with general anaesthetics and pregnancy
- Diagnosis is made by Sickledex test and Hb electrophoresis

Investigations:
Blood - FBC (Hb 6-8 g/dL usually)
- PBF (sickle cells, target cells, Howell-Jolly bodies)
Sickledex test - Specific test to identify sickle cells (HbS blood will sickle)
Hb electrophoresis/ - To detect relative quantities of HbS, HbF, HbA
Isoelectric focusing/
High-performance
liquid chromatography
Guthrie test - Newborn screening for sickle cell disease at birth

Management:
General - Folic acid 5 mg OD
- Oral penicillin daily (due to autosplenectomy)
- Triple vaccination (Pneumococcal, Hib, meningococcal)
- Regular influenza vaccination
- Avoid precipitating factors
Crises - Admit to hospital
- Check FBC, film, reticulocytes, BUSE, LFT, CRP
- CXR if respiratory symptoms/signs, ECG if chest pain
- MSU and blood cultures if infection suspected
- Strong analgesia (usually IV opiates)
- Fluid (IV, 50% above usual formula)
- Oxygen (by CPAP if necessary eg. sickle chest syndrome)
- Bed rest and keep warm
- Monitor closely (SPO2, PR, BP, RR, pain & nausea)
- IV antibiotics if infectoin present or suspected
- Transfusion if necessary (multiple may be needed)
- Exchange transfusion (↓proportion of sickle cells, indicated in severe painful
crises, neurological damage, sequestration, sickle chest syndrome,
priapism)
Surgery - Transfusions are performed pre-operatively for major surgery to ↓HbS
fraction
to <30%
- Anaesthetic care is taken to keep patient warm, well oxygenated and
hydrated, pain-free and acidosis avoided
New therapies - Bone marrow transplant or Haematopoietic Stem Cell Transplant (for severe
disease, using a haploidentical sibling match, curative)
- Hydroxyurea (↑HbF, ↓frequency of crises as early as 1 year of age)

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PART IX

ONCOLOGY
Oncology Overview
Cancers in Paediatrics:
- Neuroblastoma
- Nephroblastoma (Wilms tumour)
- Rhabdomyosarcoma
- Bone tumours
- Retinoblastoma
- Germ cell tumours
- Liver tumours (Hepatoblastoma)
- Brain tumours
- Childhood histiocytosis syndrome
- Leukaemia (Refer subsequent chapter) *Most common!
- Lymphoma (Refer subsequent chapter)

Differences between adult and childhood cancer:


Adults Childhood
- Usually arise from squamous cells eg. - Usually arise from embryonal cells eg.
- Lung - Neuroblastoma
- Breast - Nephroblastoma
- Colorectal - Hepatoblastoma
- Retinoblastoma
- Less chemosensitive, more complications - More chemosensitive, less complications
- Poorer prognosis - Better prognosis (70%)

A) Neuroblastoma
- Tumour arising from neural crest cells of the sympathetic nervous system, may develop in
- Adrenal gland (50%)
- Sympathetic chain (50%): anywhere from cranial fossa to the coccyx)
- Clinical features:
- Usually <5 years old
- Abdominal mass
- Metastatic symptoms (70%): Bone pain, Proptosis, periorbital bruising, massive
hepatosplenomegaly, skin, nodules, lymphadenopathy, weight loss, pallor, malaise
- Investigations:
- Urinary catecholamine metabolites (↑vanillylmandelic acid (VMA) and homovanillic acid (HVA)
- CT/MRI scan
- Meta-iodobenzylguanidine (MIBG) scan: cathecholamine precursor, will outline metastases
- Tissue biopsy (or positive bone marrow): necessary to confirm diagnosis & define molecular
features that determines prognosis & therapy
- Management:
- Treatment depends on child`s age, tumour stage & biology (presence/absence of amplification
of MYCN oncogene)
- Low-risk tumours (managed with surgical resection +/- chemotherapy (Subtype-Stage 4S
resolves without therapy; cure rate >90%)
- High-risk tumours (More aggressive chemotherapy, high-dose chemo with stem cell rescue,
local radiotherapy & differentiation treatment*; cure rate 10-40%) * Use of retinoic acid derivatives
to force cells to diffentiate past a point of development so that they lose capacity to grow quickly/spread)

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B) Nephroblastoma (Wilms tumour)
- Tumour of embryonic renal precursor cells, incidence is 7.8/million
- Clinical features:
- Mean age 3 years, 5% with bilateral disease at presentation
- Abdominal mass (most common presentation), abdominal pain & vomiting
- Hypertension, haematuria
- Associations: genitourinary abnormalities, overgrowth disorders (hemihypertrophy, Beckwith-
Wiedemann syndrome), aniridia, Chr11 short arm deletion involving ½ Wilms gene (eg. W1T)
- Investigations:
- Imaging (Abdominal USS, CT/MRI scan, AXR, CXR-metastasis)
- Urinalysis (haematuria)
- Staging:
I - Completely resected disease of kidney only
II - Disease beyond kidney but completely resected
III - Residual disease post-surgery or nodal involvement
IV - Metastatic disease (usually lung)
- Management: (age-dependent)
- Primary nephrectomy then chemotherapy (USA)
- Initial chemotherapy, nephrectomy (Standard in UK, Europe)
- Radiotherapy used as part of combined strategy for local residual post-surgery & pulmonary
metastatic disease
- Prognosis: (histology, disease stage, tumour size, child`s age)
- Favourable histology (89-98%, 2-year survival)
- Poor histology (17-70%, 4-year survival)

C) Rhabdomyosarcoma
- Tumour of primitive mesenchymal tissue (which striated muscle arises from), may occur
anywhere, but commonest sites are: head & neck, genitourinary tract, extremities
- Clinical features:
Head & neck tumour - Proptosis, Facial swelling
- Nasal obstruction, blood-stained nasal discharge
Genitourinary tract tumour - Urinary tract infection (UTI), Dysuria
- Blood-stained vaginal discharge
- Associations: NF-1, Beckwith-Wiedermann syndrome
- Management: (site, resectability, stage, location, histology, metastases)
- Initial surgical resection then chemotherapy
- If unresectable initially, chemotherapy, second look surgery +/- radiotherapy
- Prognosis: localised standard risk histology disease has 70% 5-year survival

D) Bone tumours
- Incidence: 5.6/million
(whites>blacks, M>F),
- Most commonly
present in adolescent
- Two most common:
- Osteosarcomas
- Ewing sarcoma

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E) Retinoblastoma
- Tumour arising in the retina. Annual incidence: ~4/million
- May be unilateral (75%) or bilateral (always hereditary)
- AD, incomplete penetrance, hereditary (40%), sporadic (60%)
- Clinical features:
- White pupillary reflex (leucoria): picked up on developmental checks
- Squint (any new squint in child should be investigated, though it is an unusual finding)
- Decreased vision
- Proptosis, raised ICP, orbital pain (advanced disease)
- Management:
- Local therapy (radiotherapy, photocoagulation/cryotherapy)
- Enucleation of eye (if unavoidable)
- Chemotherapy (reduce tumour volume prior to local therapy/if residual/metastatic cancer
- Optimised treatment which minimises radiotherapy to improve visual sparing & reduce
incidence of future secondary tumours
- Prognosis:
- Overall survival is >90%. Poor survival if extensive/metastatic disease. Familial cases have
increased incidence of 2` malignancies (osteosarcoma, soft tissue sarcoma, melanoma)

F) Germ cell tumours


- Tumours arising from primitive pluripotent germ cells which migrate from fetal yolk sac to
form gonads.
- Mostly benign, include sacrococcygeal teratoma, choriocarcinoma, seminoma, dysgerminoma.
- Sarcococcygeal teratoma:
- Most common neonatal tumour
- Clinical features:
- Rectum & urinary tract may be involved, 90% have an external component
- 10% malignant at birth, if benign teratomas left unresected malignant transformation can
occur (Malignancy defined as tumour which secretes AFP or B-hCG, has particular histological
appearance-yolk sac tumour)
- Investigations:
- Imaging (CT/MRI scan of affected area, bone scan, chest CT)
- Biological markers (↑AFP, β-hCG)
- Histology of lesion (biopsy or resection specimen)
- Management: Surgical resection (if possible). Malignant tumours should be treated with
chemotherapy before surgery to minimise morbidity
- Prognosis (excellent if benign, 60-90% 5-year survival if malignant.

G) Liver tumours
- Primary:
- Benign (hemangioma)
- Malignant
- Hepatoblastoma
(refer next page)
- HCC
- Secondary/Metastatic:
- Wilms tumours
- Neuroblastoma
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H) Hepatoblastoma

Introduction:
- Occurs predominantly in children <3 yr of age, median age of diagnosis is 1 yr
- Aetiology unknown, associate with familial adenomatous polyposis (FAP), Beckwith-
Wiedemann syndrome, hemihyperplasia, Gardner syndrome & other somatic overgrowth
syndromes (increased IGF-2 expression 2` to genetic mutations/ epigenetic changes
- All children with Beckwith-Wiedemann syndrome or hemihyperplasia should be routinely
screened with AFP levels & abdominal ultrasounds
- Prematurity & low birthweight is associated with ↑incidence, risk ↑ as birthweight ↓.
Epidemiology:
- Primary hepatic malignancies in children are rare (<2% of all pediatric malignancies)
- Hepatoblastoma accounts for majority of cases (75% of primary liver tumors)
- Approximately 100 new cases of hepatoblastoma are diagnosed each yr in US
- Usually of an advanced stage, yet adjuvant chemotherapy & total hepatectomy with
transplantation provide cure and long-term survival for the majority of patients
- Survival >85% (reported by International Society of Pediatric Oncology)
Pathogenesis:
- Arises from precursors of hepatocytes, histologically classified as whole epithelial type,
containing fetal/embryonal malignant cells (either as a mixed or pure elements)
- Mixed type contains both epithelial & mesenchymal elements
- Histologic classification has a direct correlation with clinical outcome
- Pure fetal subtype predicts a more favorable outcome
- Small cell undifferentiated subtype has normal AFP levels, predicts worse outcome
Clinical features:
- Usually presents as a large, asymptomatic abdominal mass
- Arises from right lobe 3x more often than left, usually unifocal (large, firm mass)
- Fatigue, fever, weight loss, anorexia, vomiting & abdominal pain as the disease progresses
- Rarely, it presents with hemorrhage 2` to trauma/spontaneous rupture
- Metastatic spread most commonly involves regional lymph nodes & lungs
Diagnosis:
Blood - Anaemia
- Thrombocytosis (30%)
Liver biopsy - Biopsy of liver tumour to establish diagnosis
AFP - Used in diagnosis & monitoring of hepatic tumors
- Elevated in almost all hepatoblastomas
LFT - Bilirubin & liver enzymes usually are normal
Hepatitis B & C - Usually negative in hepatoblastoma
screening
Imaging - AXR, USS to characterise the hepatic mass
- USS to differentiate malignant hepatic masses from benign vascular lesions
- CT or MRI to define extent of intrahepatic tumor involvement & potential
for surgical resection
- CT thorax to look for metastatic lesions

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Management:
- Complete resection is the definitive cure
- Max 85% resectability, hepatic regeneration noted within 3-4 months post-surgery
- Treatment is based on surgery & systemic chemotherapy using:
- Cisplatin+ vincristine+5-fluorouracil/doxorubicin
- Liver transplant is a viable option for unresectable hepatoblastoma with good long-term
survival
- Pretransplant medical condition is important predictor of outcome
- Transplant is much more effective as primary surgery than as salvage therapy
- Alternative treatment options currently under investigation include other systemic
chemotherapy agents such as carboplatin, ifosfamide, etoposide, and irinotecan
- Other treatment approaches include transarterial chemoembolization, cryoablation, and
radiofrequency ablation.
Prognosis
- Survival rates >90% in low-stage tumors (with surgery & adjuvant chemotherapy)
- Survival rates is ~60% for unresectable tumour at diagnosis
- Survival rates of ~25% for metastatic disease with complete regression by chemotherapy &
surgical resection of tumour & isolated pulmonary metastatic disease
- Long-term chemotherapy S/E: cardiac toxicity with doxorubicin, renal & ototoxicity with
cisplatin

Algorithm for the management of a child presents with a hepatoblastoma

*Consider continuation of
chemotherapy or living-related liver
transplantation if cadaveric liver
transplant not available in a timely
fashion

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I) Brain tumours
- In children, always primary.
- Divided into supratentorial & posterior fossa
(infratentorial)
- Infant <2 years : Equal frequencies of infra &
supratentorial tumours
- 2-12 years : 2/3 posterios fossa (infratentorial)

- Clinical features:
Signs of raised ICP - Morning headache, drowsiness, vomiting (esp on waking)
- Diplopia, strabismus, papilloedema (late sign)
- Nystagmus (horizontal, vertical or rotatory)
- Bulging fontanelle, macrocephaly
- Behavioral/ personality change
- Head tilting & nuchal rigidity
- Cranial nerve palsies (IV & VI)
Focal neurological signs - Complex partial seizures
- Ataxia (cerebellar tumours)
- Hemiparesis
- Endocrinopathies (eg. diabetes insipidus)

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J) Childhood Histiocytosis Syndrome
- Group of disorders involving proliferation of histiocytic cells in bone marrow of dendritic cell or
monocyte-macrophage systems
- Most are benign proliferations, some malignant. Classified based on histology:

Class I : Dendritic Langerhans` cell histiocytosis


cell disorders - Langerhans` cells (skin histiocytes with antigen-presenting function)
- They are CD1a +ve & identified on EM with cytoplasmic organelles (Birbeck
granules: like tennis rackets)
- Unknown cause. Incidence is 2-5 cases/million children, peak age 1-3 years, M>F
- Clinical features: Result of infiltration with Langerhans` cells & subsequent
immunological reaction to these cells.
Bone pain & swelling Due to isolated/ multiple lytic lesions:
- Punched-out skull lesions, mastoid necrosis with
middle ear involvement (lytic lesion)
- Jaw (floating teeth), orbit (proptosis), vertebral
fractures, long bone lesions
- Bone marrow infiltration seen
Skeletal survey should be performed at diagnosis
Skin rash Pink/brown papules becoming eczematous, scaly &
pruritic, involving face, scalip, behind ears, axillary &
inguinal fold, back & nappy area
Lung infiltration Causing cough, tachypnoea, chest pain
CXR (diffuse micronodules, later reticulonodular)
Endocrine Esp diabetes insipidus
Ear discharge, lymphadenopathy, hepatosplenomegaly
- Management:
- Single system: observation alone, topical treatment (rash), analgesia, steriods,
chemotherapy if necessary
- Multisystem: chemotherapy then BMT if necessary, eg. non-responders with
bone marrow disease
- Prognosis: worse if multisystem, >1 year old & with active disease
Class II : Hemophagocytic lymphohistiocytosis (Systemic form)
Macrophage - Primary (mutation in perforin gene, absent perforin granules in lymphocytes)
disorders - Secondary (infections, immunosuppression, far infusions or malignancy)
- Disorder involving immune dysregulation
- Diagnostic criterias:
- Fever, Splenomegaly, Pancytopenia
- High TG or low fibrinogen
- Typical histology (with haemophagocytosis)
- Others (lymphadenopathy, skin rash, LFT ↑, ferritin ↑)
- Treatment:
- Primary: chemotherapy then BMT if needed (persistent/familial disease)
- Secondary: may resolve with treatment of percipitating factors
Juvenile xanthogranuloma (Cutaneous form)
- Single or multiple yellow-orange papules, usually regress over few years
- Lipid-laden macrophages seen on histology
- Systemic involvement (most commonly ocular) is rare
Class III : Malignant - Acute monocytic leukaemia (M5)
histiocytoses of - Acute myelomonocytic leukaemia (M4)
lymphoid origin Treatment is with chemotherapy or BMT

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Leukaemia

Definition:
- Uncontrolled & abnormal hyperproliferative immature WBC, leading to bone
marrow failure & body organ infiltrated OR
- Malignant neoplasm of haemopoetic stem cell characterized by diffuse replacement of bone
marrow with neoplastic cells & leukemic cells infiltrate liver, spleen, lymph node & other tissues

Epidemiology:
- Acute leukemia is the single most common form of malignancy in children
- Incidence rate in west Malaysia ~ 3/4 per 100,000 children below the age of 13 years old
- About 70% of leukemia are ALL & about 18% is non-lymphoblastic leukemia
- CML is relatively rare in childhood

Aetiology:
- Most commonly, the aetiology is unknown
- Genetic factors
- Increased incidence in patients with chromosomal disorders (eg. Down`s syndrome, ataxia
telangiectasia, Wiskott-Aldrich syndrome & identical twins with affected parents)
- Chromosomal abnormalities:
Philadelphia chromosome in CML (95%) & sometimes ALL
- A long arm of chr22 is shortened by reciprocal translocation to long arm of chr9
- Environmental factor
- Chemicals (eg. benzene compounds used in industry)
- Drugs (eg. chemotherapy with chlorambucil & procarbazine)
- Radiation exposure (eg. nuclear generators & Rx for Hodgkin`s disease)

Pathogenesis:
- Clonal proliferation by successive divisions from a single abnormal stem/progenitor cell
- Blast cells fail to differentiate normally (non-functional cell) but are capable to further divide
- Accumulation of these cells results replacement of normal haemopoetic precursor cells of bone
marrow -> Bone marrow failure
- Immature cell with rapid infiltration to the body organ, may result in death

Classification:
- Classified on the basis of:
- Type of cell involved, Maturity of cells
- Either acute or chronic
Acute Leukemia Chronic Leukemia
- Very immature cells (blast cells) - Initially, mature leukocytes
- Rapidly fatal course - Relatively indolent course
- Subdivided into: - Subdivided into:
- Acute myeloid leukemia (AML) - Chronic myeloid leukemia (CML)
- Acute lymphoblastic leukemia (ALL) - Chronic lymphoblastic leukemia (CLL)
- Acute lymphoblastic leukaemia (ALL) (75%): peak incidence age 4 years
Acute myeloid leukaemia (AML) (20%): stable incidence <10 years, increase in adolescence
Chronic myeloid leukaemia (CML) (3%)
Juvenile CML and the myelodysplastic syndromes (2-3%, rare)
305
A) Acute Lymphoblastic Leukaemia
- Arises from early cells in the lymphoid series
- Genetic association with Down syndrome, hyperdiploidy, translocation (eg. t(9:22) Philadelphia
chromosome (poor risk)

Classification of ALL:

Clinical Features:
Organ Symptoms or Signs
General - Malaise & anorexia
Bone Marrow - Anemia: pallor, lethargy
- Thrombocytopenia: brusing, petechiae & nose/gum bleed
- Neutropenia: infection, Fever, Mouth ulcer
- Bone or joint pain: Limping)
Reticulo-endothelial system - Hepatosplenomegaly
- Lymphadenopathy
- Superior mediastinal obstruction
Other organ infiltration - CNS: headaches, vomiting, convulsions & nerve palsies
- Testis: Testicular enlargement
- Kidney: Acute renal failure

Investigations:
FBC, PBF - Anaemia (normochromic, normocytic)
- Blasts present (normally only found in bone marrow_
- WCC↓, normal or ↑
- Platelet ↓
CXR - Mediastinal mass (in T-ALL)
CSF - Blasts seen if CSF involvement
Renal function & uric acid - Impaired renal function with raised uric acid (if renal
infiltration or tumour lysis syndrome)
Special classification test - Chromosomal analysis
- Immunocytochemistry, immunophenotyping
- Ig & T-cell receptor gene rearrangement studies

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Management:

Induction of remission - Aim to kill rapidly most tumour cells to enter remission phase
- Combination therapy for 4 weeks, remission rate is 95%
- Multiagents: vincristine, danorubicin, L-asparaginase, steriod (pred/dexa)
Consolidation of - Blocks of intensive chemotherapy to consolidate remission
remission - To bring down tumour burden to very low level
- Improves cure rate BUT high risk for complications (toxicity)
- Multiagents: Ara-c, cyclophosphamide, etoposide
- CNS prophylaxis (crosses BBB), eg. intrathecal chemotherapy (MTX)
(previously used high-dose MTX & CNS radiotherapy but associate with
adverse neuropsychological side effects)
Intensification - 2-3 blocks of intensive multiagent chemotherapy to clear submicroscopic/
minimal residual disease
Maintenance - 2/3 years chemotherapy(outpatient) usually with oral 6-MP, MTX, vincristine
chemotherapy & prednisolone or dexamethasone
- Modest intensity continue over 2 years (girls) or 3 years (boys)
- Co-trimoxazole given throughout regimen to prevent Pneumocytic carinni
infection

Management of Relapse:
- Intensive chemotherapy (and cranial irradiation CNS relapse): high dose chemo +/- total body
irradiation (TBI). BMT may offer best chance of cure
- Relapse usually attacks CNS (polyphagia), testes (painless unilateral swelling), bone marrow
(pancytopenia)

307
Remission criteria:
- <5% blasts in the bone marrow OR absence of blast cells in the PBF
- Restoration of normal peripheral blood counts
- Absence of extramedullary involvement
- Child is physically well or normal

Prognostic indicators:

Ph+, 11q23

B) Acute Myeloid Leukaemia


- Arises from a pluripotent cell or myeloid progenitor committed to erythroid, granulocyte-
monocytic or megakaryocyte line
- Associate with Down syndrome, aplastic anaemia, Fanconi anaemia, previous chemotherapy

Clinical features:
Organ Symptoms or Signs
Bone marrow failure - Same as in ALL: WCC may be ↑, ↓ or normal
Others - Gum hypertrophy (esp M4 & M5)
- DIC (M3)
- Chloroma (localised mass of leukaemic cells, eg. skin,
retro-orbital epidural)
- Bone pain (less common than in ALL)

Classifications:

**

* Associated with DIC (M3)


** Characterised by leukaemic skin nodules, gum hypertrophy & CNS infiltration (M4)

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Investigations:
Same as ALL. Bone marrow must contain ≥30% blast cells (blasts may contain Auer rods)

Management:
Induction of - Chemotherapy(eg. danorubicin,cytosine arabinoside,thioguanine/etoposide
remission - >80% achieve remission. If not achieved then BMT is necessary.
Consolidation - Same as induction regimen
- Intrathecal chemo (+/- irradiation) if CNS leukaemia at diagnosis/CNS relapse
Further consolidation - Total 4-5 courses of multiagent chemotherapy (eg. etoposide, cystosine
arabinoside, m-amascrine)
- BMT is usually only considered after relapse of AML in children

Management of Relapse:
- Treated with intensive chemotherapy (and intrathecal chemotherapy & cranial irradiation in
CNS relapse). BMT offers best chance of cure.
- Common site: bone marrow (CNS rarely)

Prognosis:
- Overall cure rate is 60-70%. Cure rates depend on types (highest for M3 AML) & decrease with
increasing age.

Principle of Management:
1) General
- Correction of anaemia & thrombocytopenia by blood & platelet transfusion
- Treat infection with IV antibiotics
- Prevention of acute tumour lysis syndrome (ATLS) by giving adequate hydration & allopurinol
* ATLS resuls from massive release of cellular breakdown products consequent of tumour cell death from effective
treatment, biochemical disturbances: hyperkalemia, hyperuricaemia, hypocalcaemia, hyperphosphataemia.

2) Chemotherapy
- Acts in different ways BUT end-result is inhibit process of cell division
- Not only affect tumour cell but also normal dividing cells:
- Bone marrow suppression: anaemia, thrombocytopenia & neutropenia leads to infection
- Gastrointestinal tract ( mucositis causing mucosal ulceration)
- Germinal epithelium (sterility that may be irreversible)
- Other SE of chemotherapy:
- Loss of hair (alopecia)
- Nausea & vomiting (particularly for cisplastin because its direct action on brainstem CTZ)
- Antiemetics (metoclopramide & domperidone)
- Serotonin 5HT3 antagonists (ondansetron & granisetron)
- May cause cancer, particularly acute leukemia years after Rx
- Give