Professional Documents
Culture Documents
Algorithms in
Pediatric
Gastroenterology
Editor
Ron Shaoul, Haifa
Kainan University
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Contents
IV Contributors Gastroesophageal reflux and vomiting 44 Chronic intestinal
II
22 Neonatal vomiting pseudo-obstruction
T. Zangen; P.E. Hyman
VI Preface R. Shaoul; N.L. Jones
Z. Hochberg
24 Nausea and vomiting 46 Irritable bowel syndrome
E. Chiou; S. Misra; S. Nurko
VII Introduction P.S. Lemos; R. Shaoul
R. Shaoul
26 Recurrent vomiting and/or
regurgitation Stomach and intestine
Y. Vandenplas; R. Shaoul
Various gastrointestinal conditions 48 Protein-losing enteropathy
28 Typical and atypical reflux syndrome B. Zeisler; F.A. Sylvester
2 Abdominal pain
Y. Vandenplas; R. Shaoul
R. Arnon; S. Misra 50 Celiac disease
30 Recurrent vomiting and/or Y. Bujanover; R. Shaoul
4 Acute gastroenteritis
regurgitation and poor weight gain
A. Lo Vecchio; D. Turck; A. Guarino 52 Helicobacter pylori
Y. Vandenplas; R. Shaoul
N.L. Jones; B.D. Gold
6 Food allergy
32 Cyclic vomiting syndrome
B. Wershil; F.A. Sylvester 54 Gastrointestinal polyps
Y. Vandenplas; B.D. Gold
B. Zeisler; F.A. Sylvester
8 Failure to thrive
A. Lahad; S. Reif 56 Intestinal malabsorption – Part 1:
10 Chronic diarrhea Other motility disorders Pathogenesis and etiology
A. Guarino; E. Ruberto; Y. Finkel
Y. Finkel; A. Guarino 34 Achalasia
12 Upper gastrointestinal bleeding S. Nurko; Y. Vandenplas 58 Intestinal malabsorption – Part 2:
C.G. Sauer; B.D. Gold 36 Constipation First diagnostic steps
A. Guarino; E. Ruberto; Y. Finkel
S. Misra; H.M. Van de Vroot
14 Lower gastrointestinal bleeding
F.A. Sylvester; D. Turck 38 Dysphagia
P.E. Hyman; T. Zangen Inflammatory bowel disease
16 Malnutrition
P.S. Lemos; B. Wershil 40 Fecal incontinence 60 Inflammatory bowel disease
A. Siddiqui; O. Eshach Adiv; S. Nurko D. Turner; A.S. Day
18 Perianal disease
A.S. Day; N.L. Jones 42 Hirschsprung’s disease 62 Crohn’s disease
P.E. Hyman; T. Zangen D. Turner; A.S. Day
20 Gastrointestinal foreign bodies
I. Rosen; R. Shaoul 64 Ulcerative colitis
Kainan University
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Surgical conditions 80 Hepatitis C Pancreas
E. Granot
66 Abdominal mass 100 Acute pancreatitis
R. Udassin; A. Vromen; E. Gross 82 Elevated aminotransferases M. Wilschanski; R. Arnon
J. Garah; R. Shaoul
68 Right lower quadrant abdominal pain 102 Chronic pancreatitis
I. Sukhotnik; P.S. Lemos 84 Elevated alkaline phosphatase M. Wilschanski; R. Shaoul
R. Shaoul; J. Garah
70 Peritonitis
S. Peleg; R. Shaoul 86 Autoimmune liver disease
G. Mieli-Vergani; M. Samyn
104 Index
72 Short bowel syndrome
Y. Finkel; I. Sukhotnik 88 Sclerosing cholangitis 109 Abbreviations
G. Mieli-Vergani; M. Samyn
98 Ascites
A. Ben Tov; S. Reif
Library of Congress Cataloging-in-Publication Data Disclaimer. The statements, options and data contained in this publi- All rights reserved. No part of this publication may be translated into
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Practical algorithms in pediatric gastroenterology / editor Ron Shaoul. not of the publisher and the editor(s). The appearance of advertise- electronic or mechanical, including photocopying, recording, micro-
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Includes bibliographical references and index. products or services advertised or of their effectiveness, quality or permission in writing from the publisher.
ISBN 978-3-318-02509-5 (alk. paper) -- ISBN 978-3-318-02510-1 safety. The publisher and the editor(s) disclaim responsibility for any
(e-ISBN) injury to persons or property resulting from any ideas, methods, in- © Copyright 2014 by S. Karger AG, P.O. Box, CH–4009 Basel
I. Shaoul, Ron, editor of compilation. II. Series: Practical algorithms in structions or products referred to in the content or advertisements. (Switzerland)
pediatrics. Printed in Switzerland on acid-free and non-aging paper (ISO 9706)
[DNLM: 1. Gastrointestinal Diseases--Handbooks. 2. Adolescent. 3. Drug Dosage. The authors and the publisher have exerted every effort by Werner Druck, Basel
III Child. 4. Decision Trees--Handbooks. 5. Infant. 6. Liver to ensure that drug selection and dosage set forth in this text are in ISBN 978–3–318–02509–5
Diseases--Handbooks. 7. Pancreatic Diseases--Handbooks. WS 39] accord with current recommendations and practice at the time of pub- e-ISBN 978–3–318–02510–1
RJ446 lication. However, in view of ongoing research, changes in government
618.92’33--dc23 regulations, and the constant flow of information relating to drug ther-
2014004252 apy and drug reactions, the reader is urged to check the package insert
Kainan University
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Contributors
Orly Eshach Adiv, MD Emer Fitzpatrick Avishay Lahad, MD
IV Pediatric Gastroenterology and Nutrition Unit Consultant Paediatric Hepatologist Pediatric Gastroenerology and Nutrition Unit
Rambam Medical Center Paediatric Liver GI and Nutrition Center Pediatric B North Department
Haifa, Israel King’s College Hospital Edmond and Lili Safra Children’s Hospital
London, UK Sheba Medical Center
Ronen Arnon, MD, MHA Tel Hashomer, Israel
Associate Professor of Pediatrics and Surgery Jamal Garah, MD
Medical Director of Pediatric Hepatology and Pediatric Gastroenterology and Nutrition Unit Piedade Sande Lemos, MD, PhD
Liver Transplantation Rambam Medical Center Pediatric Gastroenterology Consultant
Recanati-Miller Transplant Institute Haifa, Israel Hospital Fernando Fonseca
Mount Sinai School of Medicine Director, Clinica CUF Cascais
New York, NY, USA Benjamin D. Gold, MD, FACG Cascais, Portugal
Pediatric Gastroenterology, Hepatology and
Efrat Broide, MD Nutrition Andrea Lo Vecchio, MD
Head of Pediatric Gastroenterology Children’s Center for Digestive Healthcare Section of Pediatrics
Institute of Gastroenterology Atlanta, GA, USA Department of Translational Medical Science
Assaf Harofeh Medical Center University of Naples Federico II
Zerifin, Israel Esther Granot, MD Naples, Italy
Kaplan Medical Center
Prof. Yoram Bujanover Rehovot and Hebrew University-Hadassah Giorgina Mieli-Vergani
Pediatric Gastroenterology Unit Medical School Professor of Paediatric Hepatology
Edmond and Lili Safra Children’s Hospital Jerusalem, Israel Consultant Paediatric Hepatologist
Sheba Medical Center Paediatric Liver, GI and Nutrition Centre
Tel Hashomer, Israel Eitan Gross, MD King’s College London School of Medicine
Pediatric Surgery Department King’s College Hospital
Eric Chiou, MD The Hebrew University Medical School London, UK
Pediatric Gastroenterology, Hepatology and Hadassah
Nutrition Jerusalem, Israel Sudipta Misra, MBBS, MD, DM
Texas Children’s Clinical Care Center Clinical Professor of Pediatrics and Chief
Houston, TX, USA Alfredo Guarino, MD Division of Pediatric Gastroenterology,
Section of Pediatrics Hepatology and Nutrition
Prof. Andrew S. Day Department of Translational Medical Science Brody School of Medicine, East Carolina University
Paediatric Gastroenterologist University of Naples Federico II Vidant Medical Center
Department of Paediatrics Naples, Italy Greenville, NC, USA
University of Otago
Christchurch, New Zealand Paul E. Hyman, MD Samuel Nurko, MD
Professor of Pediatrics, Louisiana State University Director
Anil Dhawan Chief, Gastroenterology Center for Motility and
Professor of Paediatric Hepatology Children’s Hospital Functional Gastrointestinal Disorders
Director Paediatric Liver GI and Nutrition Centre New Orleans, LA, USA Boston Children’s’ Hospital
King’s College Hospital Boston, MA, USA
London, UK Nicola L. Jones, ND, FRCPC, PhD
Departments of Paediatrics and Physiology Sarit Peleg, MD
Kainan University
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Shimon Reif, MD Anees Siddiqui, MD Prof. Dr. Yvan Vandenplas
Director Pediatric Gastroenterology Pediatric Gastroenterology
Department of Pediatrics Specially for Children/Dell Children’s UZ Brussel, Vrije Universiteit Brussel
Hadassah Medical Center Medical Center Brussels, Belgium
Jerusalem, Israel Austin, TX, USA
Holly M. Van de Voort, MD
Irit Rosen, MD Igor Sukhotnik, MD Centennial Pediatrics Murfreesboro
Pediatric Gastroenterology and Nutrition Unit Pediatric Surgery Unit Murfreesboro, TN, USA
Rambam Medical Center Bnai Zion Medical Center
Haifa, Israel Haifa, Israel Amos Vromen, MD
Pediatric Surgery Department
Eliana Ruberto, MD Francisco A. Sylvester, MD The Hebrew University Medical School
Section of Pediatrics Professor of Pediatrics and Immunology Hadassah
Department of Translational Medical Science University of Connecticut School of Medicine Jerusalem, Israel
University of Naples Federico II Attending Pediatric Gastroenterologist
Naples, Italy Connecticut Children’s Medical Center Barry Wershil, MD
Hartford, CT, USA Professor of Pediatrics
Marianne Samyn Feinberg School of Medicine at
Paediatric Liver, GI and Nutrition Centre Amir Ben Tov, MD Northwestern University
King’s College London School of Medicine Gastroenterology Unit Chief, Division of Pediatric Gastroenterology,
King’s College Hospital Dana-Dwek Children’s Hospital Hepatology, and Nutrition
London, UK Tel Aviv Sourasky Medical Center Ann and Robert H. Lurie Children’s
Sackler Faculty of Medicine, Tel Aviv University Hospital of Chicago
Cary G. Sauer, MD, MSc Tel Aviv, Israel Chicago, IL, USA
Assistant Professor of Pediatrics
Emory School of Medicine Dominique Turck, MD Prof. Michael Wilschanski
Endoscopy Director Professor of Pediatrics Director, Pediatric Gastroenterology
Children’s Healthcare of Atlanta University of Lille Hadassah University Hospital
Training Program Director, Pediatric GI Fellowship Lille, France Jerusalem, Israel
Emory Children’s Center
Atlanta, GA, USA Dan Turner, MD, PhD Tsili Zangen, MD
Head, Pediatric Gastroenterology and Pediatric Motility Service
Ron Shaoul, MD Nutrition Unit Pediatric Gastroenterology and Nutrition Unit
Associate Clinical Professor of Pediatrics Shaare Zedek Medical Center Wolfson Medical Center
Director, Pediatric Gastroenterology and The Hebrew University of Jerusalem Holon, Israel
Nutrition Unit Jerusalem, Israel
Rambam Medical Center Bella Zeisler, MD
Haifa, Israel Raphael Uddasin, MD Connecticut Children’s Medical Center
Associate Professor of Pediatric Surgery Hartford, CT, USA
Head of Pediatric Surgery Department
The Hebrew University Medical School
Hadassah
Jerusalem, Israel
VI
This is the fourth volume of the se- troenterologists and nutritionists in given problem. In the process of
ries Practical Algorithms in Pediat- the world and edited by my friend writing this book I served as the
rics. The previous volumes – Practi- Dr. Ron Shaoul, it is obvious that non-specialist lay reader. Thirty-
cal Algorithms in Pediatric Endocri- the spirit of the algorismus has five years after having completed
nology (now in its 2nd edition), been utilized to its best. my pediatric residency, I discov-
Practical Algorithms in Pediatric Practical Algorithms in Pediatric ered that pediatric gastroenterolo-
Hematology-Oncology and Practi- Gastroenterology is meant as a gy has become a sophisticated spe-
cal Algorithms in Pediatric Nephrol- pragmatic text to be used at the pa- cialty with a solid scientific back-
ogy – have become working tools tient’s bedside. The experienced ground of which I know so little. I
for many general pediatricians and practitioner applies step-by-step would still refer my patients to a
trainees in the respective pediatric logical problem-solving techniques specialist with many of the diagno-
subspecialties. for each patient individually. Deci- ses, symptoms and signs discussed
The term ‘algorithm’ is derived sion trees prepared in advance here. But, with the help of this out-
from the name of the ninth century have the disadvantage of unac- standing book, I would refer them
Arabic mathematician Algawrismi, quaintedness with the individual after an educated initial workup,
who also gave his name to ‘alge- patient. Yet, for the physician who and would be better equipped to
bra’. His ‘algorismus’ indicated a is less experienced with a given follow the specialist’s manage-
step-by-step logical approach to problem, a prepared algorithm pro- ment.
mathematical problem-solving. In vides a logical, concise, cost-effec-
reading the final product, written tive approach prepared by a spe- Ze’ev Hochberg, MD, PhD
by some of the finest pediatric gas- cialist who is experienced with the Series Editor
The field of pediatric gastroenterol- gists. There is an increasing need well as a very enriching and gratify-
ogy is rapidly expanding, and the from both trainees in pediatric gas- ing experience to interact and work
approach to diagnosis and man- troenterology and general pediatri- with everybody. I would like to
agement of the various conditions cians for simple, bedside algo- thank the series editor Professor
is continuously changing. A better rithms. Practical Algorithms in Pe- Hochberg for his guidance and sup-
understanding of the pathogenesis diatric Gastroenterology is meant port and am especially grateful to
of many gastrointestinal disorders to be a pragmatic text which classi- Freddy Brian from Karger Publish-
has led to a more physiologic ap- fies common clinical symptoms, ers for his patience and his under-
proach and the development of bet- signs, laboratory abnormalities and standing in this long process.
ter diagnosis and treatment modal- issues of management as present-
ities. Pediatric gastroenterology is ed in daily practice. I am honored Ron Shaoul, MD
quite unique compared to adult that many of the algorithms in this
gastroenterology. We are dealing book have been written by the lead-
with developmental disorders, ing experts in the area of pediatric
some of which start in utero. The gastroenterology and the surround- I would like to thank my family,
issue of growth and development is ing fields. I would like to take this my wife Ety and my children
unique for pediatrics, and therefore opportunity to thank all those who Dolev and Shaked for their
the approach to the same disease agreed to take part in this book and continuous understanding and
condition may be different between contributed their priceless experi- support.
adult and pediatric gastroenterolo- ence. It has been my privilege as
VII
Abdominal pain
2
Yes No
햲
Acute gastroenteritis
4
Assessment of dehydration 햳
Reassess dehydration
after 3–4 h
Consider the following in addition to rehydration 햷 Consider family abilities Strongly consider NG tube ORS (preferred) or i.v. fluids
to care for the child
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햲 — Definition: AGE is a decrease in the consistency of stools
쏹 햶 — Laboratory investigations that may help in the manage-
쏹 that in developing countries, zinc supplementation results in a
(loose or liquid) and/or an increase in the frequency of evacua- ment of children hospitalized with AGE include acid-base bal- clinically important reduction in the duration and severity of
tions (typically >3 in 24 h), with or without fever or vomiting. ance and electrolyte. acute diarrhea when given as an adjunct to oral rehydration
Diarrhea typically lasts less than 7 days and no longer than 14 therapy. Zinc may be given in ORS or as such. UNICEF and
days. However, a decrease in stool consistency compared to the 햷 — Therapy in adjunct to ORS may include:
쏹 WHO recommend zinc supplementation (10 mg for children <6
previous pattern is more indicative of diarrhea than the number Probiotics: a wide pattern of bacterial preparation, schedules, months of age and 20 mg in older infants and children for 10–14
of stools, particularly in the first 3 months of life. doses, and conditions have been tested. Data from several meta- days) as a universal treatment for children with diarrhea. Never-
analyses show that the effects of probiotics in acute diarrhea in theless, there is no proven clinical benefit of its use for children
햳 — Hydration assessment: the severity of AGE is reflected by
쏹 children are strain-dependent and highly significant for watery in developed countries. Further evidence is needed to establish
the degree of dehydration. The best measure of dehydration is diarrhea and viral gastroenteritis, more evident when treatment whether zinc supplementation will also be of benefit to all chil-
the percent loss of body weight. In most cases, the pre-illness is initiated early in the course of disease and more evident in dren, malnourished and well-nourished ones alike.
weight is not available, but other criteria can provide an esti- children in developed countries. Lactobacillus-GG (level of evi- In the case of vomiting, consider ondansetron. It may prevent
mate of the degree of dehydration. There is no evidence sup- dence I-A) and Saccharomyces boulardii (level of evidence II-B) the need of hospitalizing children to provide i.v. rehydration. It
porting the use of a scoring system for the management of the are the strains most widely tested and are also the most effec- should not be used routinely for outpatient children as it may
individual child. Steiner’s group systematically reviewed the tive. Lactobacillus-GG is associated with a reduced duration of increase the diarrhea.
precision and accuracy of symptoms and signs for the evalua- diarrhea, particularly that induced by rotavirus, a reduction of
tion of dehydration in young children (from 1 month to 5 years; risk for persistent diarrhea (lasting >7 days) and a short duration
see table). The most useful signs for predicting 5% dehydration of hospitalization. It may not be effective for bacterial diarrhea. Selected reading
or more were an abnormal capillary refill time, abnormal skin Racecadotril (Acetorphan): an antisecretory drug that exerts its
turgor, and abnormal respiratory pattern. Cool extremities, a antidiarrheal effects by inhibiting intestinal enkephalinase, Guarino A, Albano F, Ashkenazi S, et al: ESPGHAN/ESPID
weak pulse, or the absence of tears are also helpful indicators of thereby preventing the breakdown of endogenous opioids (en- Guidelines for the management of acute gastroenteritis in chil-
dehydration. Sunken eyes, dry mucous membranes, an increased kephalins) in the GI tract and reducing the secretion of water dren in Europe. J Pediatr Gastroenterol Nutr 2008; 46:s1–s22.
heart rate, a sunken fontanelle in young infants, and an overall and electrolytes into the gut. Racecadotril was highly effective Guarino A, Lo Vecchio A, Canani RB: Probiotics as prevention
poor appearance were less helpful in evaluating dehydration. in reducing the volume and frequency of stool output and in and treatment for diarrhea. Curr Opin Gastroenterol 2009; 25:
reducing the duration of diarrhea (particularly in children with 18–23.
햴 — Rehydration: oral rehydration is the first-line treatment of
쏹 rotavirus diarrhea). Guarino A, Lo Vecchio A, Pirozzi MR: Clinical role of diosmec-
AGE. Several solutions have been proposed to restore hydra- Smectite: a natural hydrated alumino-magnesium silicate that tite in the management of diarrhea. Expert Opin Drug Metab
tion in children with acute diarrhea worldwide. The classical binds to digestive mucus and has the ability to bind endo- and Toxicol 2009; 5: 433–440.
full-strength WHO-ORS contains 90 mmol/l Na. The so-called exotoxins, bacteria, and rotavirus. It reduces the duration of Harris C, Wilkinson F, Mazza D, et al: Evidence guidelines for
‘reduced osmolarity solution’, which is the current WHO-ORS, diarrhea and is effective in abdominal pain. the management of diarrhea with or without vomiting chil-
contains 75 mmol/l Na+. The so-called ‘hypotonic osmolarity Zinc: since intestinal losses of zinc are considerably increased dren. Aust Fam Physician 2008; 37: 22–29.
solution’ is recommended by ESPGHAN for European children during acute diarrhea, a number of trials evaluated the effect of Steiner MJ, DeWalt DA, Byerley JS: Is this child dehydrated?
with AGE and contains 60 mmol/l Na+. When oral rehydration is zinc supplements on diarrheal diseases. The findings suggest JAMA 2004; 291: 2746–2754.
not successful because of vomiting, enteral rehydration via the
NG route is as effective as i.v. rehydration. Enteral rehydration
is associated with fewer adverse events and a shorter hospital
stay compared with i.v. therapy and is successful in most chil-
dren. Children who take ORS should not be given i.v. fluids.
Table. Assessment of severity of dehydration
햵 — Indications for hospital admission: the recommendations
쏹
for hospital admission are based on consensus and include any None or minimal Moderate Severe
of the following conditions:
Normal capillary refill Delayed capillary refill (3 – 4 s) Very delayed capillary refill (>4 s)
• Caregivers cannot provide adequate care at home and/or there
Skin pinch retracts immediately Skin pinch retracts slowly (1 – 2 s) Skin pinch retracts very slowly (>2 s)
are social or logistical concerns Normal respiratory pattern Increased respiratory rate Deep, acidotic breathing
• Newborn age Normal conscious state Restless, irritable Lethargic, unconscious
• Shock Normal drinking Drinks eagerly, increased thirst Unable to drink
5 • Severe dehydration (>9% of body weight) Normal urine output Tachycardia No urine output for >12 h
• Neurological abnormalities (lethargy, seizures, etc.) Deeply sunken eyes
• Intractable or bilious vomiting These signs correspond to These signs correspond to These signs correspond to
• Suspected surgical condition <5% lost body weight 5 – 10% lost body weight >10% lost body weight
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Various gastrointestinal conditions A. Lo Vecchio · D. Turck · A. Guarino Acute gastroenteritis
Various gastrointestinal conditions B. Wershil · F.A. Sylvester Food allergy
햲
Food allergy
6
Careful history and physical
examination 햳
Referral to allergist
for skin prick testing 햹
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Various gastrointestinal conditions B. Wershil · F.A. Sylvester Food allergy
Various gastrointestinal conditions A. Lahad · S. Reif Failure to thrive
햲
Failure to thrive
8 History and physical examination 햳
Primary Secondary
Laboratory test 햶
CBC, liver function, protein, albumin,
BUN, creatinine, electrolytes, iron, celiac profile,
TSH, HIV, urinalysis, stool culture and stool for fat
and reducing substance
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햲 — FTT is the failure to gain weight appropriately. FTT is a
쏹 햵 — The initial management of children with FTT is a high ca-
쏹 Selected reading
descriptive term and not a specific diagnosis. There are no con- loric intake. The healthy infant requires an average of 100 kcal/
sensus criteria to define this description, but most authors kg per day, but children with FTT should receive an up to 50% Frank DA, Zeisel SH: Failure to thrive. Pediatr Clin North Am
agree that a weight below the 3rd percentile for age and gender increase in the recommended daily caloric intake (as suggested 1998; 35: 1187–1206.
for two occasion measurements or a decrease of 2 percentile according to the patient’s age and gender). The number of calo- Jaffe AC: Failure to thrive: current clinical concepts. Pediatr
lines using the standard growth chart of the National Center of ries per 100 ml of formula can be increased by adding less wa- Rev 2011; 32: 100–107.
Health Statistic (NCHS) is considered as FTT. In severe cases, ter to the formula or by adding more carbohydrates in the form Kliegman RM, et al: Nelson Textbook of Pediatrics, ed 18.
linear growth and head circumference may also be affected by of glucose polymers or fat (for example, in the form of MCT or Philadelphia, Saunders, 2007, pp 184–187.
FTT. A wide variety of medical problems and psychosocial corn oil). For young children or older infants, the increase in Maggioni A, Lifshitz F: Nutritional management of failure to
stressors can contribute to FTT. However, the underlying cause the caloric intake can be achieved by using high-caloric food. thrive. Pediatr Clin North Am 1995; 42: 791.
is typically insufficient caloric intake. FTT can cause persistent The child with FTT should be followed up until a weight gain is Perrin E, et al: Criteria for Determining Disability in Infants
short stature and growth abnormalities, secondary immunodefi- demonstrated and sustained. and Children: Failure to Thrive. Evidence Report/Technology
ciencies, impaired neurological functionality and behavioral Assessment No. 72. AHRQ Publication No. 03-E026. Rockville,
problems. 햶 — The laboratory evaluation should be guided by the
쏹 Agency for Healthcare Research and Quality, 2003.
patient’s history and physical findings. Evaluations should be Wright CM: Identification and management of failure to thrive:
햳 — The key to the initial evaluation is the careful record of
쏹 carried out after failure to gain weight because a minority of a community perspective. Arch Dis Child 2000; 82: 5–9.
the patient’s history and the patient’s physical examinations. the children with FTT has abnormal laboratory findings. If no Wright CM, et al: Effect of community based management in
History and physical examinations provide valuable clues to the weight gain is achieved despite adequate caloric intake and if failure to thrive: randomised controlled trial. BMJ 1998; 317:
reason leading to FTT: ‘primary’/nonorganic FTT or ‘secondary’/ there is no finding in history or physical examination, then a 571–574.
organic FTT. Most chronic diseases may contribute to FTT. The laboratory evaluation should be made. The evaluation should
patient’s history should include detailed information about the include some of the most common diseases that can cause FTT
patient’s medical history including pregnancy and delivery time, without other noticeable symptoms.
family history, information about dietary and feeding practices
and social details. The physical examination should provide 햷 — Ask the parents to write down the amounts and the types
쏹
clues as to the severity of FTT and to any possible organic dis- of food and drinks the child ingests for at least 3 days. Observe
eases that may contribute to FTT. The interaction between the the interaction between the infant and his parents especially
child and his parents should be observed as it may be very sig- during feeding. Watch how the child eats and if there are diffi-
nificant as to the cause of FTT (especially during feeding). culties with different types of food.
Chronic diarrhea
10
Stop oral/enteral feeding and observe 햲
Diarrhea persists 햳
No Yes
CDG type II
Yes No
Macroscopic endoscopy findings detected that No lesions present 햴 Esophageal varices present 햵
are likely responsible for upper GI bleed 햳
Endoscopic therapy for ulcers if present Consider VCE for evaluation of possible small Perform endoscopic banding procedure and/or
Use 2 of the following methods: intestinal bleed sclerotherapy
Thermal coagulation (heater or multipolar probes) Consider oral PPI, monitor closely, follow-up Workup for liver disease or other causes of portal
Injection with epinephrine hypertension (i.e. vascular abnormalities)
Endoscopic clipping
Continue PPI Consider small bowel enteroscopy if lesions Follow-up endoscopy with repeat banding Consider oral PPI, monitor closely,
Treat H. pylori if present present on VCE Consider prevention follow-up
Consider serum gastrin level Consider advanced imaging such as MR or CT Consider surgical management Consider EGD
angiography, or RBC scan if bleeding persists
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Causes of upper gastrointestinal bleeding in children managed conservatively if there is no significant drop in hemoglobin. bleeding persists, advanced radiographic imaging is suggested and
Understanding the causes of upper GI bleeding in infants, children, and Swallowed blood, esophagitis, gastritis, and Mallory-Weiss tears often could include MR angiography, CT angiography, or RBC scan depend-
adolescents is helpful in dictating the management, which can vary do not cause a significant drop in hemoglobin. However, the latter three ing on the local radiographic expertise. Octreotide may be useful in
from conservative monitoring to advanced endoscopic therapies. The etiologies can, particularly if chronic, cause iron deficiency with or with- pediatric vascular anomalies, which can often be diagnosed with VCE.
following reviews the most common causes as well as the manage- out anemia. If there is a history that may suggest swallowed blood, eval-
ment of upper GI bleeding in the pediatric population. uation for epistaxis or previous surgical site is warranted. Mallory-Weiss 햵 — Endoscopic therapy for variceal bleeding includes sclerotherapy
쏹
Swallowed blood, usually from a non-GI source, can often be a cause tears are most often self-limiting and rarely cause a significant drop in and EVL. The use of both medical therapy with octreotide and EVL may
of suspected upper GI bleeding and can occur in any pediatric age hemoglobin or need endoscopic therapy. Mild/moderate esophagitis give superior results for the management of variceal bleeding at least
group. For example, neonates may spit up or vomit blood due to swal- and gastritis may cause upper GI bleeding but can often be controlled in adults. Once endoscopic therapy for varices is performed, repeat
lowing maternal blood from cracked nipples or blood in breast milk with high-dose acid suppression and monitoring, although endoscopy EVL is often necessary and prophylactic medical therapy with beta-
due to a ruptured blood vessel or from delivery. The most common may be helpful to confirm the diagnosis. Sucralfate (carafate) may be blockers should be considered despite a paucity of data in children.
reason for swallowed blood in childhood is epistaxis, which can also helpful initially if the lesions are gastric in their location as it reacts with
be seen at any age but is most common in the school-aged population, acid to form a viscous paste-like substance; however, once acid suppres- Selected reading
i.e. 6- to 12-year-olds. Any recent otolaryngological or maxillofacial sur- sion is initiated, it is unlikely to provide significant benefit.
gery including tonsillectomy or other oropharyngeal surgery may also If there is a significant drop in hemoglobin, further evaluation for the Banares R, Albillos A, Rincon D, Alonso S, Gonzalez M, Ruiz-del-Arbol
result in swallowed blood, and the presentation thereof can be delayed cause of bleeding is warranted and treatment can be initiated during this L, Salcedo M, Molinero LM: Endoscopic treatment versus endoscopic
by as much as 10–14 days. Most importantly, emesis of swallowed evaluation. Most importantly, the evaluation for liver disease with a thor- plus pharmacologic treatment for acute variceal bleeding: a meta-
blood, albeit occasionally appearing large in volume, does not result in ough history, physical examination, and laboratory assessment can sug- analysis. Hepatology 2002;35:609–615.
a decrease in the patient’s hemoglobin level. gest esophageal varices and help plan endoscopic treatment with band- Calvet X, Vergara M, Brullet E, Gisbert JP, Campo R: Addition of a
Esophagitis, gastritis, and PUD can be classified as mucosal abnormali- ing and/or sclerotherapy. Simple blood tests evaluating liver enzymes second endoscopic treatment following epinephrine injection im-
ties of the upper GI tract and can result in both microscopic and macro- (AST/ALT) and liver function (albumin, PT/PTT) can often be most helpful proves outcome in high-risk bleeding ulcers. Gastroenterology 2004;
scopic bleeding. Gastritis and esophagitis will typically result in mini- in determining whether liver disease is likely to play a role. If no liver 126:441–450.
mal, sometimes chronic, bleeding, while PUD (either gastric or duode- disease is present, endoscopy will often identify a lesion and endoscopic D’Amico G, Pagliaro L, Pietrosi G, Tarantino I: Emergency sclerother-
nal ulcers) with erosion into the underlying vessels can result in acute therapy should be planned and available at the time of endoscopy. apy versus vasoactive drugs for bleeding oesophageal varices in cir-
upper GI bleeding with large volumes at times. While bleeding may Initial treatment with pre-endoscopic resuscitation including blood prod- rhotic patients. Cochrane Database Syst Rev 2010;3:CD002233.
stop with acid blockade treatment in esophagitis and gastritis, ulcer ucts and medical management is essential, with endoscopic therapy Dorward S, Sreedharan A, Leontiadis GI, Howden CW, Moayyedi P,
disease with vessel involvement often requires endoscopic therapy. planned within 12–24 h. Medical therapy including acid suppression is Forman D: Proton pump inhibitor treatment initiated prior to endo-
A Mallory-Weiss tear of the lower esophagus or proximal stomach re- recommended, and, while there is little data in children, adult studies scopic diagnosis in upper gastrointestinal bleeding. Cochrane Data-
sults from forceful vomiting and can cause a large amount of bleeding. suggest it may reduce the need for endoscopic therapy. Sucralfate may base Syst Rev 2006;4:CD005415.
A hiatal hernia may predispose to a Mallory-Weiss tear, and eating dis- also be helpful in the initial treatment, although once acid suppression Dubois J, Rypens F, Garel L, Yazbeck S, Therasse E, Soulez G: Pediat-
orders are often associated with Mallory-Weiss tears. Bleeding typical- therapy is initiated, there may be little to no benefit. Octreotide, a so- ric gastrointestinal vascular anomalies: imaging and therapeutic is-
ly stops spontaneously, and therapy (epinephrine injection with cauter- matostatin analogue, causes vasoconstriction and is not typically recom- sues. Pediatr Radiol 2007;37:566–574.
ization) is only necessary if bleeding does not stop spontaneously. En- mended for ulcer-related upper GI bleeding. Endoscopic evaluation of- Gotzsche PC, Hrobjartsson A: Somatostatin analogues for acute
doscopy often reveals small lower esophageal lacerations. ten reveals the cause for significant upper GI bleeding. The most com- bleeding oesophageal varices. Cochrane Database Syst Rev 2008;
Esophageal/gastric varices result from portal hypertension often, but mon causes in children remain esophageal varices and ulcers or other 3:CD000193.
not always, associated with liver disease. Extrahepatic portal obstruc- mucosal abnormalities detected on endoscopy. Kay MH, Wyllie R: Therapeutic endoscopy for nonvariceal gastroin-
tion including portal vein thrombosis may also be a cause of varices testinal bleeding. J Pediatr Gastroenterol Nutr 2007;45:157–171.
without a history of preexisting liver disease. Varices often result in 햳 — Endoscopic therapy for nonvariceal bleeding can include injec-
쏹 Lau JY, Leung WK, Wu JC, Chan FK, Wong VW, Chiu PW, Lee VW,
significant bleeding, and urgent endoscopic therapy is required. tion, coagulation, and placement of hemostatic clips. Epinephrine is Lee KK, Cheung FK, Siu P, Ng EK, Sung JJ: Omeprazole before en-
Other less common causes of upper GI bleeding in children can include most commonly used for mucosal bleeding stasis and should be inject- doscopy in patients with gastrointestinal bleeding. N Engl J Med
erosions due to chronic NSAID administration, Helicobacter pylori infec- ed in four quadrants around the bleeding lesion. Thermal coagulation 2007;356:1631–1640.
tion, foreign body ingestion, caustic substance ingestion, infections, Dieu- can be performed with multipolar probes or heater probes depending Marmo R, Rotondano G, Piscopo R, Bianco MA, D’Angella R, Cipol-
lafoy’s lesions, or small bowel vascular anomalies. Other rare causes of on the availability. Heater probes have the disadvantage of deeper tis- letta L: Dual therapy versus monotherapy in the endoscopic treat-
upper GI bleeding may be congenital malformations such as intestinal sue penetration with a risk of perforation, while multipolar probes have ment of high-risk bleeding ulcers: a meta-analysis of controlled trials.
duplications, gastric or pancreatic heterotopic tissue, and gastrinoma as- limited deep tissue penetration. Hemostatic clips can be placed on ul- Am J Gastroenterol 2007;102:279–289; quiz 469.
sociated with Zollinger-Ellison syndrome or MEN type 1, which leads to cers; however, the size (<2 mm in diameter) and location of the lesion Molleston JP: Variceal bleeding in children. J Pediatr Gastroenterol
excessive gastrin/acid production resulting in severe ulceration. as well as the endoscopist’s expertise may limit their use. The combi- Nutr 2003;37:538–545.
13 nation of an endoscopic treatment (coagulation, hemostatic clip) and Singhi S, Jain P, Jayashree M, Lal S: Approach to a child with upper
Management of upper gastrointestinal bleeding in children epinephrine injection is superior to epinephrine injection alone; how- gastrointestinal bleeding. Indian J Pediatr 2013;80:326–333.
With the most common causes of upper GI bleeding in children in ever, endoscopic treatment alone may be sufficient. Villanueva C, Piqueras M, Aracil C, Gomez C, Lopez-Balaguer JM,
mind, management can be initiated with conservative measures in Gonzalez B, Gallego A, Torras X, Soriano G, Sainz S, Benito S, Balan-
many children. 햴 — If no lesions are identified at endoscopy, VCE may be consid-
쏹 zo J: A randomized controlled trial comparing ligation and sclerother-
Kainan University
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Various gastrointestinal conditions C.G. Sauer · B.D. Gold Upper gastrointestinal bleeding
Various gastrointestinal conditions F.A. Sylvester · D. Turck Lower gastrointestinal bleeding
햲
Lower gastrointestinal bleeding
14
Melena – black tarry stool, usually Hematochezia 햳 – bright red blood per rectum Occult GI bleeding – detected due to iron
indicates upper GI bleeding deficiency anemia and positive fecal blood
No Yes No
Abnormal Normal
Neonate, 0–1 months Infant, 1 month to 2 years Preschool, 2–5 years Child and adolescent
Anal fissure Hemorrhoids Well appearing Ill child Well appearing Ill child Well appearing Ill child Same as preschool
Very common Uncommon Swallowed NEC – X-ray Allergic colitis – Intussuscep- Infectious Infectious diarrhea – IBD –
in all ages in children maternal Malrotation change formula tion – X-ray, diarrhea – stool culture ileocolonoscopy
blood – Apt test and volvolus – Infectious US, barium stool culture Same as <2 years
Foods and drugs that can cause Coagulopathy – imaging diarrhea – enema Juvenile polyp –
the stool to appear bloody test Hirschsprung stool culture HUS – blood colonoscopy
Antibiotics enterocolitis – Meckel’s diver- and urine testing
Bismuth preparations rectal biopsy ticulum – scan HSP – urine,
Beets Lymphonodular endoscopy
Chocolate hyperplasia – Meckel’s diver-
Gelatin
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햲 — LGIB: bleeding distal to the ligament of Treitz.
쏹 햶 — Differential diagnosis of LGIB: the diagnosis can be de-
쏹 Selected reading
rived from an understanding of the mechanism of bleeding, the
햳 — Hematochezia: the passage of bright red blood per rec-
쏹 age of the patient, and the location of the bleeding. Mechanical- Balachandran B, Singhi S: Emergency management of lower
tum. ly, bleeding can be caused by trauma, ischemia, and inflamma- gastrointestinal bleed in children. Indian J Pediatr 2013; 80:
tion (which are all usually painful) or coagulopathy, vascular 219–225.
햴 — Medical history: information should include:
쏹 malformations, and tumors (which are all usually painless). Barnert J, Messmann H: Diagnosis and management of lower
• Family history: allergy, IBD, polyposis syndromes, vascular Therefore, interrogating the patient and family for pain associ- gastrointestinal bleeding. Nat Rev Gastroenterol Hepatol 2009;
malformations, bleeding disorders. ated with bleeding can narrow down the differential diagnosis 6: 637–646.
• Child history: neonatal history of omphalitis, sepsis, umbilical significantly. Certain causes of bleeding are more common in Khurana AK, Saraya A, Jain N, et al: Profile of lower gastroin-
catheterizations – risk factors for portal vein thrombosis lead- infants and young children (e.g. allergic proctocolitis, intussus- testinal bleeding in children from a tropical country. Trop Gas-
ing to portal hypertension. History of abnormal bleeding or ception, Meckel’s diverticulum, vascular malformations) and troenterol 1998; 19: 70–71.
liver disease. Past episodes of GI hemorrhage. Recent use of other causes are more common in older children (IBD, polyps, McCollough M, Sharieff GQ: Abdominal surgical emergencies
nonsteroidal anti-inflammatory agents or any other medica- varices, rectal trauma). Bright red blood is typical of distal co- in infants and young children. Emerg Med Clin North Am
tions. Vascular skin lesions. History of abdominal or perianal lonic bleeding; the blood will be darker the more proximal the 2003; 21: 909–935.
trauma, pain with defecation. Ingestion of red foods or fluids source of bleeding is (although large-volume hemorrhage from Teach SJ, Fleisher GR: Rectal bleeding in the pediatric emer-
that can be confused with blood. the upper digestive tract can look red). The diagnosis of the gency department. Ann Emerg Med 1994; 23: 1252–1258.
• Characteristics of bleeding: duration of bleeding and amount source of bleeding can be confirmed once the patient has been Tuck D, Michaud L: Lower gastrointestinal bleeding; in Klein-
of blood, consistency of stool, color of blood, blood mixed/ hemodynamically stabilized with a combination of colonoscopy, man RE, Goulet O, et al (eds): Pediatric Gastrointestinal Dis-
coating stool/drips, presence of blood in toilet paper but not imaging, and VCE, as necessary. ease, ed 5. Hamilton, Decker, 2008, pp 1309–1319.
in the stool.
• Associated symptoms: abdominal pain, fever, diarrhea,
urgency, tenesmus, weight loss.
15
햲
Malnutrition
16
Classification 햳
Kainan University
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햲 — Malnutrition is an abnormality in food intake that can lead
쏹 햵 — A general assessment of the child is essential for deter-
쏹 햻 — Hospital admission – in the case of severe malnutrition, it
쏹
to varying pathologic states; its clinical features are a result of an mining the cause of malnutrition, and thus how to approach the serves two purposes: first to slowly restart a nutritional inter-
imbalance of essential nutrients, calories, and/or energy. Accord- issue: 60% of cases have some form of environmental depriva- ventional program in order to avoid potentially serious refeed-
ing to thermodynamic laws, total energy expenditure (including tion, approximately 20% are organic in nature, and no cause is ing electrolyte complications, and second to evaluate the causes
basal metabolic rate, physical activity, thermic effect of feeding, found in 20%. Often, there is no simple way to discern among of malnutrition in a controlled setting. It is important to appreci-
and growth) must be in balance with total energy intake. Energy these possibilities, so it is useful to approach the assessment of ate that the lack of a natural environment might complicate the
needs change during the course of life, with growing infants and the etiology in physiologic terms, using the concept of the body assessment of the child-family interaction.
children having greater energy requirements than adults. How- as a furnace. The causes of undernutrition can then be divided
ever, at any point in time, if there is negative energy balance, into footnotes 6–8. 햽 — Ambulatory treatment – close follow-up – remember that
쏹
undernutrition occurs. Likewise, consistent positive energy bal- very often nonorganic and organic causes of malnutrition coex-
ance will lead to excessive weight gain and obesity. 햶 — On physical examination, the general appearance and
쏹 ist and both must be addressed. Establish routines for daily life
activity/interactions of the child may give an idea of whether events, not only for meal times. Increase caloric concentration
햳 — In general, the most used and practical markers of under-
쏹 there is an organic cause for malnutrition or not. It is important of the meals the child is having and avoid juices and nibbling.
nutrition are weight less than the 3rd percentile or weight less to assess the cognitive abilities and neurodevelopment stage. Consider caloric and vitamin supplements.
than 2 SD for the percentile of the height. Malnutrition was first Careful attention should be given to the child’s interaction with
defined in terms of a deficit in weight for a child’s age. Howev- parents and others as indirect signs of neglect can manifest as a
er, height for age and weight for height are often more useful lack of parental interest in the child, no affection, or no visual Selected reading
tools for assessing acute and chronic malnutrition. For example, contact. Look for signs of abuse, such as scars, ecchymoses, or
a low weight for height is seen in acute malnutrition, whereas in hematomas. It is important to take notice of dysmorphic facies, Ahmed T, Ali M, Ullah MM, et al: Reduced mortality among
chronic undernutrition there are frequently no clinical signs oth- mouth breathing, increased thyroid size, wheezing, heart mur- severely malnourished children with diarrhoea through the
er than low height and weight for age. Children who are over murs, increased liver or spleen, abdominal distension, or abnor- use of a standardized management protocol. Lancet 1999; 353:
90% of their expected weight for height and less than 90% of malities in the neurological examination. Nutritional assess- 1919–1922.
their expected height for age are termed nutritional dwarfs be- ment should be performed by the same trained examiner on Berhamn RE, Kliegman R, Jenson HB (eds): Nelson Textbook
cause their height has been stunted but their weight is appropri- every single visit and always under the same conditions with of Pediatrics, ed 17. Philadelphia, Saunders, 2004.
ate for their height. In developed countries, stunting is unusual height, weight, weight for height, or BMI plotted as appropriate. Figueira F, Alves J, Bacelar C: Desnutrição energético-proteica;
and one can use different classifications, the most common be- Skinfold thickness is important especially in children with neu- in: Manual de Diagnostico Diferencial em Pediatria, ed 2. Rio
ing weight for height until 2 years of age and BMI after 2 years rological conditions due to the difficulty in assessing length, de Janiero, Guanabara Koogan, 2005.
of age. In developing countries, extremes of undernutrition oc- weight, or BMI. If possible, observe a meal with the child and its Fuchs G, Ahmed T, Araya M, Baker S, Croft N, Weaver L: Mal-
cur that are not normally seen in developed countries. Maras- parents. nutrition: Working Group report of the second World Congress
mus is seen after severe nutritional deprivation, primarily of cal- of Pediatric Gastroenterology, Hepatology, and Nutrition. J
ories, and is characterized by growth retardation and wasting of 햷 — Decreased intake as in feeding errors, bad habits, food
쏹 Pediatr Gastroenterol Nutr 2004; 39(suppl 2):S670–S677.
muscle and subcutaneous fat. In kwashiorkor, deficiency in pro- refusal with organic cause (esophagitis, gastritis, dysphagia, Gomez F, Galvan RR, Cravioto J, Frenk S: Malnutrition in in-
tein intake exceeds that of calories, and thus edema accompa- cerebral palsy, oro-motor problems, syndromic disorders), or fancy and childhood, with special reference to kwashiorkor.
nies muscle wasting, so that weight alone may underestimate without cause (nonorganic): neglect, abuse, child-parent inter- Adv Pediatr 1955; 7: 131–169.
the degree of malnutrition. action problems. Hendricks K, Duggan C: Nutritional assessment: clinical evalu-
ation; in Becker BC (ed): Manual of Pediatric Nutrition, ed 4.
햴 — A detailed medical and dietary history is an essential com-
쏹 햸 — Increased losses as in vomiting and/or diarrhea (GERD,
쏹 Morrison’s Health Care, 2005.
ponent of the diagnosis and assessment of malnutrition yet is gastritis, Helicobacter pylori, food allergies (cow’s milk)) and in Management of Severe Malnutrition: A Manual for Physicians
often neglected or incomplete. It should include reliable obser- malabsorptive diseases (most commonly, celiac disease, CF, and Other Senior Health Workers. Geneva, World Health Orga-
vations of the child’s activity level, social interactions, and sleep giardiasis, duodenitis, hepatic disease). nization, 1999.
pattern. The number and types of infections should be noted. A McLean DS, Read WWC: Weight/length classification of nutri-
family history with consideration of parental weight and height 햹 — Increased energy expenditure/poor use as in fever, malig-
쏹 tion status. Lancet 1975; 2: 219–221.
may provide insight into genetic issues. A personal medical his- nancy, CF, hyperthyroidism, renal disease, cardiac disease, pul- Ramos R: History and dietary intake; in Koletzko B (ed): Pediat-
tory can reveal organic pathology, perinatal events, and diges- monary disease, storage disease, metabolic disease. Even with ric Nutrition in Practice. Basel, Karger, 2008.
tive system problems. Additionally, psychosocial features might organic causes, there is sometimes an overlap in terms of phys- Waterlow JC: Classification and definition of protein calorie
give clues to possible causes of malnutrition, such as an abusive iopathology: for instance in CF, there might be anorexia of malnutrition. BMJ 1972; 3: 565–567.
17 or neglectful environment. Diet evaluation as a separate compo- chronic disease, malabsorption, and increased energy expendi-
nent of the history is critical. Inquire about attitude and knowl- ture due to the work of breathing.
edge as well as the amounts, types, and frequencies of food be-
ing provided. Ask specifically about types and qualities of liquid 햺 — Assessment and evaluation – the findings on history,
쏹
Kainan University
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Various gastrointestinal conditions P.S. Lemos · B. Wershil Malnutrition
Various gastrointestinal conditions A.S. Day · N.L. Jones Perianal disease
Perianal disease
18 Perianal symptoms 햲
Kainan University
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햲 — Perianal symptoms are used to describe any symptom
쏹 햸 — Excoriation can be due to frequent watery motions or to
쏹 Selected reading
around the anus. These include itching, redness, pain, fissure, specific conditions such as lactase deficiency (where motions
perianal abscess, fistula, hemorrhoids or rectal prolapse. are acidic). It is important to exclude local infection. Treat un- Ezer SS, et al: Perianal abscess and fistula-in-ano in children:
derlying reason for loose stools (if possible). Protect the peri- aetiology, management and outcome. J Paediatr Child Health
햳 — Refer to other causes of perianal problems given in the
쏹 anal skin (barrier creams) and allow for adequate drying of the 2010; 46: 92–95.
algorithm. skin. Festen C, van Harten H: Perianal abscess and fistula-in-ano in
infants. J Pediatr Surg 1998; 33: 711–713.
햴 — Typical perianal fissures in the midline: 90% at 6 o’clock.
쏹 햹 — Functional constipation in children is often associated
쏹 Kokx NP, Comstock JA, Facklam RR: Streptococcal perianal
These may be associated with skin tags. with pain and/or anxiety leading to withholding of stool. Peri- disease in children. Pediatrics 1987; 80: 659–663.
anal fissure can be consequent to the passage of hard stool ini- Poenaru D, Yazbeck SV: Anal fistula in infants: etiology, fea-
햵 — Atypical tags may occur outside the midline, at any posi-
쏹 tially or subsequently. Consider local topical therapy (such as tures, management. J Pediatr Surg 1993; 28: 1194–1195.
tion. preparation containing local anesthetic and/or steroid) in con- Serour F, Gorenstein A: Characteristics of perianal abscess
junction with oral stool-softening therapy. and fistula-in-ano in healthy children. World J Surg 2006; 30:
햶 — Fungal infection of the perianal region occurs often in
쏹 467–472.
conjunction with the perineum and should be considered in in- 햺 — CD may involve the perianal region in 10–15% of individ-
쏹 Stermer E, Sukhotnic I, Shaoul R: Pruritus ani: an approach to
fancy. Satellite lesions may be present. Swab for microbiologi- uals with CD. This can occur as the presenting feature or devel- an itching condition. J Pediatr Gastroenterol Nutr 2009; 48:
cal confirmation of fungal infection and treat with topical anti- op subsequently. Manifestations include atypical fissures, large/ 513–516.
fungals. multiple skin tags, fistulae and/or perianal abscess formation.
19
Location
Esophagus 햸 Pharynx
Proximal Distal to
to pylorus pylorus
At the Object
Kainan University
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Endoscopic Follow-up Surgery Endoscopic If not out Surgery Immediate Removal Trial of 1 mg Wait Immediate Immediate Immediate Conservative
removal removal sponta- removal glucagon 12–24 h removal removal removal follow-up,
(consider neously, involve
overtube) 햷 surgery surgeons
햲 — History
쏹 햴쏹
쏹 햵쏹
햶쏹햷 — A foreign body in the stomach or duodenum Selected reading
• What (which object, how many objects, size, shape, radio- should be treated according to the object’s type (special consid-
opaque)? eration for narcotic packets, batteries, and magnets), diameter, Ayantunde AA, Oke T: A review of gastrointestinal foreign
• Radiolucent (fish/chicken bones, wood, plastic, most glass, length and whether the object is sharp or not. For sharp objects, bodies. Int J Clin Pract 2006; 60: 735–739.
thin metal objects). removal with an overtube should be considered. There is indica- Betalli P, Rossi A, Bini M, Bacis G, Borrelli O, Cutrone C, et al:
• When? Who witnessed? tion for urgent retrieval of multiple magnets when localized in Update on management of caustic and foreign body ingestion
• Complaints (when started, progression, drooling, vomiting, the stomach. Close clinical follow-up if they have passed the in children. Diagn Ther Endosc 2009; 2009: 969868.
cough, dysphagia, dyspnea, dysphonia, pain in neck/chest/ pylorus and immediate surgical approach if the patient be- Hussain SZ, Bousvaros A, Gilger M, Mamula P, Gupta S,
abdomen). comes symptomatic are needed. Kramer R, et al: Management of ingested magnets in children.
• Signs (fever, desaturation). J Pediatr Gastroenterol Nutr 2012; 55: 239–242.
• Specific questions about past GI surgeries, congenital abnor- 햸쏹
쏹 햹쏹
햺쏹햻 — In general, no foreign body should remain in the Ikenberry SO, Jue TL, Anderson MA, Appalaneni V, Banerjee
malities. esophagus for more than 24 h. Immediate interventions should S, Ben-Menachem T, et al: Management of ingested foreign
• When there is food impaction, investigate whether there is a be made according to the location of the foreign body (upper bodies and food impactions. Gastrointest Endosc 2011; 73:
known esophageal pathology (stricture/past surgery). third), length of time since ingestion, type of foreign body (more 1085–1091.
• If not, search for motility problems, neuromuscular disease, than one coin, sharp objects, batteries) and if the patient is Uyemura MC: Foreign body ingestion in children. Am Fam
achalasia, scleroderma, EoE, severe infections, GERD. symptomatic. Endoscopic removal is also indicated for asymp- Physician 2005; 72: 287–291.
tomatic patients, especially if they present with other pathologi- Waltzman ML: Management of esophageal coins. Curr Opin
햳 — Radiological studies
쏹 cal conditions such as CD or past surgical interventions, which Pediatr 2006; 18: 571–574.
• X-ray: A-P and lateral. could limit foreign body progression through the digestive tract.
• Barium swallow (gastrographin when perforation suspected).
• CT (regularly not needed).
21
22
Bilious vomiting
Yes No
Yes No
Malrotation and midgut volvulus R/O pyloric stenosis 햲 Other proximal malformations GER/GERD
Intestinal atresia/webs Consider upper GI barium study Inborn errors of metabolism 햳
Meconium ileus Congenital adrenal hyperplasia
HD Milk/soy allergy 햴
NEC Systemic infections
Neurological disorders 햵
Child abuse
23
햲
Nausea and vomiting
24
Physiopathology 햳 History 햴 Physical examination 햵
Clinical features 햶
Causes 햷
Age 햸 GI Non-GI 햹
<3 weeks 3 weeks – 3 years 3 years – adult Infection Inflammation Obstruction Motility Other
GER Gastroenteritis Gastroenteritis Gastroenteritis GER Pyloric stenosis Achalasia CNS – tumor, increased ICP, drugs
GERD Celiac disease Appendicitis Peritonitis Gastritis Congenital anomalies HD Infection – meningitis, UTI,
Gastroenteritis Peptic disease/GERD Migraine Appendicitis Peptic ulcer Malrotation + volvulus Pseudo-obstruction pneumonia, OM, sepsis
Food allergy Food allergies Peptic disease Hepatitis Celiac disease Intussusception Gastroparesis Metabolic – galactosemia,
Pyloric stenosis Appendicitis Pancreatitis Eosinophilic Foreign bodies, bezoars urea cycle deficiency, porphyria
Malformations Obstruction Cholecystitis disease Meconium ileus Endocrine
Systemic infections Metabolic disorder Hepatitis Food allergy Incarcerated hernia Anorexia Toxic
Metabolic disease Increased ICP Bulimia Pancreatitis Bulimia Heart failure
Increased ICP Respiratory infections IBD Cyclic vomiting Renal – obstruction, renal insufficiency
Pregnancy Pregnancy
Increased ICP
Kainan University
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햲 — Nausea is the sensation that one has when about to vom-
쏹 햶 — Vomiting is very common in children and quite often the
쏹 햿 — Abdominal CT is not a very useful imaging test in the
쏹
it. Vomiting is defined as the expulsion of the gastric contents only presenting sign of many diseases. It might be a defense evaluation of the vomiting child by itself but is helpful for ab-
through the mouth with variable intensity. Regurgitation is the mechanism to expel unwanted ingested toxins, an alteration in scesses and tumors.
effortless exit of small amounts of gastric content through the the vomiting center due to increased ICP, or the consequence
mouth. of intestinal obstruction, anatomical changes, mucosal inflam- 헀 — Upper endoscopy is very useful to assess mucosal in-
쏹
mation, or a generalized metabolic disorder. flammation and lesions and to obtain biopsies for microscopy
햳 — The stimuli that lead to vomiting can be quite varied and
쏹 and cultures.
can be divided into: (a) motility disturbances, (b) activated vagal 햷 — The etiology of vomiting can be classified in different
쏹
reflex, (c) direct stimulation of the CNS, or (d) vestibular system ways: 헁 — Ask for a surgical consultation whenever there is any sus-
쏹
stimulation. From the motility causes within the GI system (a), picion of a surgical pathology.
the most common are the ones that lead to slow gastric empty- 햸 — By age, dividing the main ages into: (a) neonatal period
쏹
ing (such as GERD, gastroparesis, cyclic vomiting), viral infec- (newborn up to 3 weeks of age) with a variety of causes but, in
tions (rotavirus, calicivirus, EBV, viral hepatitis), bacterial infec- the first days of life, with special attention to malformations, Selected reading
tions (UTI, sepsis, GI infections), allergic disease and metabolic systemic infections, and metabolic diseases and then to UTI,
disease. The vagal reflex (b) can be stimulated through direct pyloric stenosis, and reflux; (b) from 3 weeks to 3 years with Murray KF, Christie DL: Vomiting. Pediatr Rev 1998; 19: 337–
mucosal irritation (stomach and esophagus), but there are many gastroenteritis, celiac disease, allergies, and reflux disease, and 341.
other psychological stimuli that elicit vomiting through the va- (c) from 3 years to adult with gastroenteritis, appendicitis, and Ramos AG, Tuchman DN: Persistent vomiting. Pediatr Rev
gal route. Vomiting through direct stimulation of the vomiting others. 1994; 15: 24–31.
center in the CNS (c) through drugs, altered vascularization, ner- Richards CA, Andrews PL: Emesis as a model system for the
vous stimuli or mass compression can be worrisome and diffi- 햹 — By causes related to or outside the GI system. Within the
쏹 study of functional bowel disease. J Pediatr Gastroenterol
cult to diagnose. Not very common in children, there is also GI system, it is important to further divide into obstructive ver- Nutr 2007; 45(suppl 2):S120–S126.
vestibular system stimulation (d) as in labyrinthitis and vertigo. sus nonobstructive causes. Vandenplas Y, Rudolph CD, Di LC, Hassall E, Liptak G, Mazur
L, et al: Pediatric gastroesophageal reflux clinical practice
햴 — As in any aspect of medicine, the history gives us very
쏹 햺 — After the appropriate history and physical examination
쏹 guidelines: joint recommendations of the North American So-
important clues regarding the importance of vomiting: age of are completed, a careful differential diagnosis is elaborated, and ciety for Pediatric Gastroenterology, Hepatology, and Nutrition
onset, frequency, time of the day, interval between crisis and screening and disease-related tests should be performed to con- (NASPGHAN) and the European Society for Pediatric Gastro-
whether totally asymptomatic in between crisis, any precipitant firm or rule out the diagnosis. enterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr
factor like cough or crying, whether vomiting is easily elicited or Gastroenterol Nutr 2009; 49: 498–547.
even provoked (‘easy vomiter’), or whether there is any relation- 햻 — Laboratory studies can include a CBC – if anemia is
쏹
ship with feeding and relevant aspects of choking, aspiration, found, one should think of gastritis, esophagitis, or PUD; iono-
and grunting. The content of the vomit can be a sign of immedi- gram and blood gas alterations are seen in pyloric stenosis and
ate attention, whether it contains blood, mucus, bile, or food. metabolic disease; an increase in transaminases, bilirubin, and
Always ask for an association with other symptoms such as fe- GGT may indicate hepatobiliary disease. In cases of severe
ver, diarrhea, abdominal distension, irritability, headache, vomiting and pain, always check the amylase level for pancre-
weight loss, visual disturbances, and sleep disturbances. A de- atitis. Urinalysis might lead to the diagnosis of pyelonephritis.
tailed dietary history with the introduction of different foods can
be indicative of some pathology. Inquire about family history of 햽 — X-ray without contrast as in plain abdominal and chest
쏹
PUD, allergies, and migraine and whether other members of the X-ray might help to rule out obstruction and pneumonia; when
family have the same symptoms. performed with oral contrast (UGIS), it helps to identify anatom-
ical defects (malrotation, intussusception, or volvulus).
햵 — When examining a vomiting child, it is very important to
쏹
immediately evaluate the hydration status and act upon it if nec- 햾 — Abdominal US is very useful to assess hepatic, gallblad-
쏹
essary. Also assess the child’s nutritional status by measuring der, biliary tree, kidney, pancreas, and ovary processes. It is also
weight, height, and BMI. Blood pressure measurement might the gold standard for pyloric stenosis and is very useful to iden-
be important. Focusing on the abdominal examination, look for tify abdominal abscesses and to rule out appendicitis and intus-
distension, bowel sounds, pain, peritoneal signs, and masses. susception.
25 Always perform a neurological examination looking for menin-
geal signs, fontanel, balance, and fundoscopy.
No Yes
No Yes
Resolves by 18 months
No Yes
Consultation with pediatric gastroenterologist, A healthy child Further evaluation Further evaluation
Kainan University
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Since the severity of symptoms differs substantially in patients 쏹
Recurrent regurgitation/vomiting and normal weight in children Selected reading
with reflux, three different algorithms (i.e. this algorithm, the aged <8 years: a history and physical examination should al-
typical and atypical reflux syndrome algorithm, and the recur- ways be performed. Forbes D: Mewling and puking: infantile gastroesophageal re-
rent vomiting and/or regurgitation and poor weight gain algo- • Infant without warning signals: flux in the 21st century. J Paediatr Child Health 2013; 49: 259–
rithm, see pp. 28 and 30, respectively) are proposed. If the case is not troublesome, no further investigations are nec- 263.
essary. Recommendations include the instruction of parents Katz PO, Gerson LB, Vela MF: Guidelines for the diagnosis and
The infant with frequent regurgitation. about warning signals, reassurance, anticipatory guidance, con- management of gastroesophageal reflux disease. Am J Gas-
Regurgitation, spitting-up, posseting and spilling are synonyms, tinuation of breast-feeding, and thickened feeding (AR formula). troenterol 2013; 108: 308–328.
and are defined as the passage of refluxed gastric contents into If the symptoms persist for more than 18 months, an endoscopy Vandenplas Y: Challenges in the diagnosis of gastroesopha-
the pharynx, mouth and sometimes expelled out of the mouth. and a biopsy via UGIS should be performed. geal reflux disease in infants and children. Expert Opin Med
The happy spitter: since more than 50% of 3- to 4-month-old in- If the case is troublesome, the same applies as in a ‘not trouble- Diagn 2013; 7: 289–298.
fants regurgitate at least once a day, regurgitation is considered some’ case. In addition, the follow-up should be organized, par- Vandenplas Y, Gottrand F, Veereman-Wauters G, De GE,
‘physiologic’ in this age group. No diagnostic investigations are ent-infant interactions observed, and, if symptoms persist, en- Devreker T, Hauser B, et al: Gastrointestinal manifestations of
recommended if the infant is thriving well and has no other doscopy and biopsy or 2-week PPI trial should be considered. cow’s milk protein allergy and gastrointestinal motility. Acta
symptoms than simple regurgitation. Therefore, parental reas- If there is an allergy, extensive hydrolysates are recommended. Paediatr 2012; 101: 1105–1109.
surance and anticipatory guidance are the cornerstone of the Vandenplas Y, Rudolph CD, Di LC, Hassall E, Liptak G, Mazur
management. Explaining the physiologic nature and the natural L, et al: Pediatric gastroesophageal reflux clinical practice
evolution of disappearance will help the parents. No dietary guidelines: joint recommendations of the North American So-
changes are recommended in the breast-fed infant if the mother ciety for Pediatric Gastroenterology, Hepatology, and Nutrition
is feeding her baby in an appropriate way. The pros and cons of (NASPGHAN) and the European Society for Pediatric Gastro-
thickening the formula or, if available, antiregurgitation formula enterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr
should be considered. Possible advantages are that the parental Gastroenterol Nutr 2009; 49: 498–547.
observation of decreased regurgitation will contribute to their Table 1. Symptoms and signs that may be associated with GER
reassurance. Possible disadvantages are nutritional conse-
quences since a thickened formula has a different composition Symptoms
than an ‘optimal’ starter formula. Recurrent regurgitation with/without vomiting
The distressed infant with frequent regurgitation: symptoms due Weight loss or poor weight gain
to GER are troublesome when they have an adverse effect on Irritability in infants
the well-being of a pediatric patient. To be defined as GERD, re- Ruminative behavior
flux symptoms must be troublesome to the infant, child or ado- Heartburn or chest pain
Hematemesis Table 2. Warning signals
lescent and not simply troublesome for the caregiver. Regurgita-
tion and vomiting may be difficult to separate in this group. Any Dysphagia, odynophagia
Wheezing Bilious vomiting
proposed diagnostic and therapeutic guideline in this group may GI bleeding
Stridor
be challenged because there is no evidence for a ‘best manage- Hematemesis
Cough
ment’, mainly because of the lack of data. In principle, the same Hematochezia
Hoarseness
recommendations are valid in this group, but the coping of the Consistently forceful vomiting
parents is challenged much more. Moreover, some of these Signs Onset of vomiting after 6 months of life
symptoms may be caused by other conditions such as cow’s Esophagitis Failure to thrive
milk allergy, UTI, etc. If there is associated poor weight gain, in- Esophageal stricture Diarrhea
vestigations and/or a different therapeutic intervention will be Barrett esophagus Constipation
recommended (refer to the recurrent vomiting and/or regurgita- Laryngeal/pharyngeal inflammation Fever
tion and poor weight gain algorithm, see p. 30). Recurrent pneumonia Lethargy
Anemia Hepatosplenomegaly
The 1- to 8-year-old child presenting with regurgitation and Dental erosion Bulging fontanelle
Feeding refusal Macro-/microcephaly
vomiting: most guidelines and recommendations do not con-
Dystonic neck posturing (Sandifer syndrome) Seizures
sider the group beyond the age of the natural disappearance of
27 Apnea spells Abdominal tenderness or distension
infant regurgitation and before the age when history is reliable.
Apparent life-threatening events Documented or suspected genetic/metabolic syndrome
There are no data to evaluate the ‘best management’ in this
age group.
28
Improvement
Yes No
Discontinue PPI
Relapse
Kainan University
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햲 — The pediatric patient with typical reflux syndrome: in old-
쏹 Table 1. Symptoms and signs that may be associated with GER Selected reading
er children above the age of 8–12 years, management can be ac- in older children
cording to adult recommendations. After history and physical Forbes D: Mewling and puking: infantile gastroesophageal re-
examination, a 2-week therapeutic trial with a PPI as the diag- Symptoms flux in the 21st century. J Paediatr Child Health 2013; 49: 259–
nostic-therapeutic intervention may be the best option in this Recurrent regurgitation with/without vomiting 263.
group. However, data in this age group are missing. Weight loss or poor weight gain Katz PO, Gerson LB, Vela MF: Guidelines for the diagnosis and
Ruminative behavior management of gastroesophageal reflux disease. Am J Gas-
햳 — The pediatric patient with extraintestinal/atypical mani-
쏹 troenterol 2013; 108: 308–328.
Heartburn or chest pain
festations: although many children are treated for reflux pre- Vandenplas Y: Challenges in the diagnosis of gastroesopha-
Hematemesis
senting with extraesophageal manifestations, the evidence is geal reflux disease in infants and children. Expert Opin Med
Dysphagia, odynophagia
limited. There are indeed many studies reporting on a high inci- Diagn 2013; 7: 289–298.
Wheezing
dence of abnormal results of reflux investigations in children Vandenplas Y, Gottrand F, Veereman-Wauters G, De GE,
Stridor
presenting with chronic otorhinologic or respiratory symptoms. Devreker T, Hauser B, et al: Gastrointestinal manifestations of
Cough cow’s milk protein allergy and gastrointestinal motility. Acta
However, there are almost no intervention trials. Hoarseness
A demonstration of a time-related association between symp- Paediatr 2012; 101: 1105–1109.
toms and reflux episodes seems, at this stage, the best option Signs Vandenplas Y, Rudolph CD, Di LC, Hassall E, Liptak G, Mazur
for this group. However, non-acid as well as acid reflux may be Esophagitis L, et al: Pediatric gastroesophageal reflux clinical practice
the culprit in this patient group. Today, therapeutic options are Esophageal stricture guidelines: joint recommendations of the North American So-
almost restricted to acid-reducing medications, except for sur- ciety for Pediatric Gastroenterology, Hepatology, and Nutrition
Barrett esophagus
gery. Moreover, parameters evaluating symptom associations (NASPGHAN) and the European Society for Pediatric Gastro-
Laryngeal/pharyngeal inflammation
have been validated in adults but not in children. At this stage, enterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr
Recurrent pneumonia
impedance may be the best option. Gastroenterol Nutr 2009; 49: 498–547.
Anemia
Dental erosion
29
Warning signals
No Yes
No Yes
Assess for FTT (see failure to thrive algorithm, p. 8), consider UGIS
Abnormal
No Yes
Improved
No Yes
Consultation with pediatric gastroenterologist, consider acid Education, close follow-up Treat accordingly Involve dietician, Further evaluation
Kainan University
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The approach to a child with recurrent vomiting and/or regurgi- Table 1. Warning signals Selected reading
tation and poor weight gain is similar to that outlined in the re-
current vomiting and/or regurgitation algorithm (p. 26), i.e. ob- Bilious vomiting Forbes D: Mewling and puking: infantile gastroesophageal re-
taining the patient’s history, performing a physical examination GI bleeding flux in the 21st century. J Paediatr Child Health 2013; 49: 259–
and identifying warning signals. If there is associated poor Hematemesis 263.
weight gain, investigations and/or a different therapeutic inter- Hematochezia Katz PO, Gerson LB, Vela MF: Guidelines for the diagnosis and
vention and dietician involvement are recommended. The ‘best management of gastroesophageal reflux disease. Am J Gas-
Consistently forceful vomiting
approach’ depends on the clinically most suspected diagnosis troenterol 2013; 108: 308–328.
Onset of vomiting after 6 months of life
and/or possibilities to perform diagnostic investigations. Al- Vandenplas Y: Challenges in the diagnosis of gastroesopha-
Failure to thrive
though two double-blind placebo-controlled trials with PPIs in geal reflux disease in infants and children. Expert Opin Med
Diarrhea
distressed infants provided negative results, some of these in- Diagn 2013; 7: 289–298.
Constipation
fants suffered painful GER. Therefore, a time-limited therapeutic Vandenplas Y, Gottrand F, Veereman-Wauters G, De Greef E,
Fever Devreker T, Hauser B, et al: Gastrointestinal manifestations of
trial with acid-reducing medication is acceptable. There is no Lethargy
evidence suggesting that prokinetics may be of interest in this cow’s milk protein allergy and gastrointestinal motility. Acta
Hepatosplenomegaly Paediatr 2012; 101: 1105–1109.
group. In other situations, endoscopy with biopsies and/or pH- Bulging fontanelle
metry or impedance to demonstrate a time relation between Vandenplas Y, Rudolph CD, Di LC, Hassall E, Liptak G, Mazur
Macro-/microcephaly L, et al: Pediatric gastroesophageal reflux clinical practice
reflux and symptoms may be considered. However, since the Seizures
‘distress’ will improve over time, parental reassurance remains guidelines: joint recommendations of the North American So-
Abdominal tenderness or distension ciety for Pediatric Gastroenterology, Hepatology, and Nutrition
the cornerstone. ‘Treat and observe’ versus ‘diagnostic proce-
Documented or suspected genetic/metabolic syndrome (NASPGHAN) and the European Society for Pediatric Gastro-
dures’ largely depend on local possibilities. In case of FTT, di-
etary management is advised, which may be thickened formula, enterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr
formula with increased caloric density, extensive hydrolysates Gastroenterol Nutr 2009; 49: 498–547.
or amino acid-based feeding, NG tube feeding, etc.
31
33
햲
Achalasia (Dysphagia, vomiting of undigested food, respiratory problems)
34
Exclude anatomic/mucosal problem
Barium swallow
Endoscopy 햳
Esophageal motility 햴
Response to therapy
No Yes
Barium swallow
Manometry
Endoscopy 햿
Esophagitis
Kainan University
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햲 — Patients with achalasia present with dysphagia for both
쏹 햹 — PD has been shown to be an effective long-term therapy.
쏹 Selected reading
liquids and solids, vomiting of undigested food, or respiratory Most patients will require more than one dilatation, but a 50%
symptoms. Odynophagia is not a characteristic presenting sign. long-term response has been described. The major risk associ- Chuah SK, Hsu PI, Wu KL, Wu DC, Tai WC, Changchien CS:
ated with PD is perforation, which has been described in 5% of 2011 update on esophageal achalasia. World J Gastroenterol
햳 — Anatomic and mucosal diseases need to be excluded. En-
쏹 the cases. 2012; 18: 1573–1578.
doscopy will show if there is mucosal disease like peptic esoph- Corda L, Pacilli M, Clarke S, Fell JM, Rawat D, Haddad M: Lap-
agitis or EoE. A barium swallow will delineate the anatomy and 햺 — Heller myotomy, with or without fundoplication, has be-
쏹 aroscopic oesophageal cardiomyotomy without fundoplica-
show any strictures. The barium swallow may show variable de- come the standard of care in many institutions since the advent tion in children with achalasia: a 10-year experience: a retro-
grees of esophageal dilatation with tapering at the esophageal of laparoscopic/thoracoscopic surgery. The decision to perform spective review of the results of laparoscopic oesophageal
junction, which is sometimes referred to as beaking, but it may a simultaneous fundoplication is center dependent but should cardiomyotomy without an anti-reflux procedure in children
be negative in early achalasia. not be done routinely. Surgery has been associated with a 95% with achalasia. Surg Endosc 2010; 24: 40–44.
long-term response, and the main long-term complications Hussain SZ, Thomas R, Tolia V: A review of achalasia in 33
햴 — If the barium study is suggestive of achalasia or if it is
쏹 have been reflux and dysphagia (when associated with a fundo- children. Dig Dis Sci 2002; 47: 2538–2543.
normal and there is no other explanation, the next diagnostic plication). The decision to perform either PD or myotomy is de- Jung C, Michaud L, Mougenot JF, Lamblin MD, Philippe-
step is the performance of an esophageal manometry. The diag- pendent on family wishes and the expertise available at the dif- Chomette P, Cargill G, Bonnevalle M, Boige N, Bellaïche M,
nosis of achalasia always needs to be confirmed manometrical- ferent centers, but surgery is slowly becoming the first-line Viala J, Hugot JP, Gottrand F, Cezard JP: Treatments for pedi-
ly, and the following are the manometric diagnostic criteria: treatment. atric achalasia: Heller myotomy or pneumatic dilatation? Gas-
(a) Lack of esophageal peristalsis in the distal esophagus. (b) troenterol Clin Biol 2010; 34: 202–208.
Abnormal LES function – abnormal or absent relaxation; even 햻 — If there is no response to treatment, the patient needs to
쏹 Pensabene L, Nurko S: Approach to the child who has persis-
though a lack of LES relaxation is usually seen, there are pa- be restudied to establish the reason for the failure, and repeat tent dysphagia after surgical treatment for esophageal achala-
tients in whom there may be an apparent complete LES relax- therapy or new therapy should be considered. The differential sia. J Pediatr Gastroenterol Nutr 2008; 47: 92–97.
ation in some swallows. (c) High resting LES – many children diagnosis includes inadequate treatment or severe esophageal Rosen R, Nurko S: The esophagus: motor disorders; in Walker
with achalasia may have normal LES pressure. (d) High esopha- dysmotility. WA, et al (eds): Pediatric Gastrointestinal Disease, ed 4. Phila-
geal pressure compared with gastric pressure. The hallmark of delphia, Decker, 2004, pp 424–462.
the diagnosis is a lack of esophageal peristalsis. 햽 — If there is response to therapy, close follow-up is needed.
쏹
A repeat barium swallow a few weeks after therapy is recom-
햵 — If the manometry is not diagnostic of achalasia, other di-
쏹 mended.
agnoses need to be considered, such as nonspecific motility dis-
orders, systemic illnesses, or psychiatric problems. 햾 — If there is relapse of the symptoms, a careful workup is
쏹
needed. The most common reasons for the recurrence of the
햶 — Even though there is no specific treatment for achalasia,
쏹 symptoms are outlined in footnote 14.
there are treatments that have been designed to improve
esophageal emptying. There are four main modalities. 햿 — The evaluation of the patient includes the performance
쏹
of a barium study, endoscopy, and esophageal manometry.
햷 — The treatment of achalasia is multifaceted. Supportive
쏹 This combination will allow the establishment of the underlying
treatment is instituted. This includes nutritional support, correc- pathophysiology of the symptoms. A correlation between
tion of electrolyte problems, control of the pain, and symptom- esophageal emptying and LES pressure needs to be estab-
atic maneuvers to avoid aspiration. Occasionally, it may be nec- lished. An LES pressure <10 mm Hg is usually considered a
essary to pass an NG tube to provide nutritional support until it success after treatment.
is safe to use other invasive therapies.
헀 — The most common reasons of recurrent symptoms are
쏹
햸 — Pharmacologic treatments have been employed with lim-
쏹 the presence of esophagitis, dysphagia resulting from the ab-
ited long-term success. The main drugs used have been calcium normal esophageal motility, fibrosis at the area of previous
channel blockers. Drugs are a temporary way to treat achalasia treatment, or recurrence or persistence of achalasia. Depending
until more definitive treatments are employed. Injection of botu- on the nature of the problem, new medical therapy, PD, or sur-
linum toxin to the LES has been shown to be an effective short- gery may be indicated (see footnote 10).
35 term treatment of achalasia. Given the short duration of re-
sponse, it is now considered a temporary treatment or a modal-
ity used as a clinical tool to establish the diagnosis when the
diagnosis is not certain.
햲
Constipation
36
Functional Organic
Disimpaction
Monitoring 햶
Anorectal manometry 햸
HD
Anatomical abnormalities
Slow transit* Pelvic floor Anal achalasia Metabolic diseases
dyssynergia** (ultrashort segment HD)**
Studies Treatment
Kainan University
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햲
쏹 — Functional constipation is diagnosed according to Rome 햷 — Barium enema screening in older children with constipa-
쏹 Selected reading
III diagnostic criteria. tion has low yield and is a poor predictor of an abnormal bari-
um enema. Lumbosacral spine MRIs may show lesions such as de Lorijn, et al: The Leech method for diagnosing constipation:
햳 — History includes passage of meconium within 24 h of
쏹 tethered cord, tumors, and sacral agenesis. intra- and interobserver variability and accuracy. Pediatr
birth, onset with potty training, change of diet, stress, and re- Radiol 2006; 36: 43–49.
ported encopresis. 햸 — An anorectal manometry can exclude HD and diagnose
쏹 Kanterman RY, et al: Pediatric barium enema examination:
megarectum and pelvic floor dyssynergia. optimizing patient selection with univariate and multivariate
햴 — Physical examination includes short stature/anemia (ce-
쏹 analysis. Pediatr Radiol 1994; 24: 288–292.
liac), cerebral palsy, anorectal malformations, and neurologic 햹 — These treatments not only show benefit in children with
쏹 Liem O, et al: Novel and alternative therapies for childhood
deficits. mental retardation or cerebral palsy but also in normal children. constipation. Curr Gastroenterol Rep 2007; 9: 214–218.
Longstreth GF, et al: Rome III diagnostic criteria. Gastroenter-
햵 — Benefits of behavioral modification are less clear in chil-
쏹 햺 — A successful program requires a team approach consist-
쏹 ology 2006; 130: 1480–1491.
dren. Professional counseling may be beneficial. ing of a biofeedback therapist, a dietician, and a behavioral psy- van Dijk M, et al: Chronic childhood constipation: a review of
chiatrist so that children learn how to normalize abnormal def- the literature and the introduction of a protocolized behavioral
햶 — Stool logs are key for compliance, altering treatment, and
쏹 ecation dynamics along with anorectal manometry. intervention program. Patient Educ Couns 2007; 66: 63–77.
identifying nonresponders. van Ginkel R, et al: The effect of anorectal manometry on the
outcome of treatment in severe childhood constipation: a ran-
domized, controlled trial. Pediatrics 2001; 108:E9.
Wong AL, et al: Impact of cecostomy and antegrade colonic
enemas on management of fecal incontinence and constipa-
tion: ten years of experience in pediatric population. J Pediatr
Surg 2008; 43: 1445–1451.
Yousseff NN, Di Lorenzo C: Childhood constipation: evaluation
and treatment. J Clin Gastroenterol 2001; 33: 199–205.
37
햲
Dysphagia
38 Medical and feeding history
Physical examination 햳
Barium
swallow
Normal
Developmental Cleft palate Hypoxic brain damage Oropharyngeal Reflux Stenosis Reflux Psychological Functional Achalasia
dysphagia Craniofacial Myasthenia gravis incoordination esophagitis Stricture disease dysphagia 햾 dysphagia 햿 Esophageal spasm
syndromes Congenital myotonic Cricopharyngeal EoE Web Scleroderma
dystrophy achalasia Infectious Foreign body Dysautonomia
Head trauma esophagitis Tumor
Kainan University
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햲 — Dysphagia is defined as difficulty in swallowing. Accurate
쏹 햷 — Impaired oropharyngeal swallowing may be associated
쏹 햽 — If no structural or mucosal abnormality is found, manom-
쏹
pain complaints are difficult to elicit in infants, young children with aspiration and chronic airway disease as well as recurrent etry is indicated. Most nonstructural causes of esophageal dys-
and children with limited cognitive abilities. Untreated dyspha- or chronic pneumonia. In case of proven aspiration, oral feeding phagia are due to abnormal esophageal motility. There are pri-
gia may be associated with food refusal, FTT, aspiration pneu- is replaced by enteral tube feeding to ‘bypass’ swallowing. In mary esophageal motility disorders: achalasia is probably the
monias and/or inability to maintain proper nutrition and hydra- some cases, swallowing may improve (developmental improve- best known of these and is well defined by the absent esopha-
tion. ment or rehabilitation after trauma) and oral feeding can be re- geal peristalsis and impaired deglutitive LES relaxation. Diffuse
sumed. or distal esophageal spasm and nonspecific esophageal motility
햳 — Impaired swallowing can be due to oropharyngeal or
쏹 disorder are associated with dysphagia in a few children.
esophageal dysfunction. History and physical examination of 햸 — Esophageal mucosal lesions often present as dysphagia.
쏹 Esophageal motility disorders occur in cases of esophageal in-
anatomic and neurologic abnormalities should explore for non- Upper GI endoscopy is the optimal study to identify mucosal volvement in systemic diseases, e.g. familial dysautonomia,
esophageal causes. Symptoms of choking, cough, gagging, cya- lesions. Peptic esophagitis due to esophageal acid exposure, scleroderma, CIP and graft-versus-host disease.
nosis, posturing of head and neck during eating, or food aver- EoE due to food allergy and infectious esophagitis (CMV, can-
sion and feeding difficulties are suggestive of swallowing disor- dida, herpes) are the most common causes of esophageal mu- 햾 — Several psychiatric conditions are associated with dys-
쏹
ders. Impaired neuromuscular coordination of swallowing cosal inflammation. phagia. Dysphagia may occur as a phobia following a frighten-
(cerebral palsy, congenital myotonic dystrophy, neurodegenera- ing, sensitizing or choking experience with food. It may also oc-
tive disorders, myasthenia gravis, Chiari malformation, head 햹 — Esophageal intrinsic narrowing may be caused by con-
쏹 cur as part of an anxiety disorder. Finally, dysphagia may be the
trauma), abnormalities of the head and neck (mass, goiter) or genital stenosis or web, acquired strictures (peptic, eosinophilic, presentation of an eating disorder, not otherwise specified.
abnormalities of the oral cavity (macroglossia, cleft palate, caustic ingestion, dermatological disorders), postfundoplication
micrognathia) are supportive of oropharyngeal dysphagia. and tumors or after surgical repair for esophageal atresia. Ex- 햿 — The Rome criteria for functional dysphagia must be ful-
쏹
trinsic compression by a vascular ring may also present as dys- filled for the preceeding 3 months, with symptom onset at least
햴 — Oropharyngeal dysphagia can be a transient phenome-
쏹 phagia (dysphagia lusoria). Evaluations for structural lesions 6 months prior to diagnosis, and include the following: (1)
non in infants upon the introduction of solid food. It is usually include upper GI endoscopy and barium swallow, even with no Sense of solid and/or liquid foods sticking to, lodging in, or
associated with mild motor developmental delay or sensory endoscopic abnormality. passing abnormally through the esophagus. (2) Absence of evi-
hypersensitivity. Diagnostic procedures are seldom indicated, dence that GER is the cause. (3) Absence of achalasia.
and the symptoms resolve spontaneously. 햺 — Isolated cricopharyngeal dysfunction is a rare motility
쏹
disorder in infants and children. Most patients present with
햵 — Esophageal dysphagia occurs with solid food only, or
쏹 feeding difficulties at birth or till 6 months of age. Diagnosis is Selected reading
with both solids and liquids. The associated symptom of odyno- aided by barium swallow and manometry. Clinical improvement
phagia is highly suggestive of esophageal ulceration. may occur spontaneously or after cricopharyngeal dilatations. Owen W: ABC of the upper gastrointestinal tract. Dysphagia.
BMJ 2001; 323: 850–853.
햶 — Videofluoroscopy, or modified barium swallow, is the
쏹 햻 — In the absence of structural or mucosal abnormalities,
쏹 Spechler SJ: AGA technical review on treatment of patients
procedure of choice for evaluating the patient with impaired concomitant symptoms of heartburn or regurgitation suggest with dysphagia caused by benign disorders of the distal
swallowing. Swallowing is assessed by visualizing the passage that esophageal sensitivity to acid may be the cause of the dys- esophagus. Gastroenterology 1999; 117: 233–254.
of barium-impregnated liquids, pastes and pureed foods phagia. Resolution of the dysphagia with PPI therapy implies Tutor JD, Gosa MM: Dysphagia and aspiration in children.
through the oral cavity, pharynx and esophagus. Fluoroscopy that the dysphagia was a manifestation of reflux disease. Pediatr Pulmonol 2012; 47: 321–337.
provides objective evidence of oral and pharyngeal dysfunction
and detects aspiration. Videofluoroscopy aids in assessing the
bolus characteristics (size and consistency) that make food safe
to swallow.
39
햲
Fecal incontinence
History 햴 : Congenital anomaly? Objective of therapy 햳
Postsurgical? Social continence
40 Traumatic injury? Predictability
Independence
No Yes
No Yes
Kainan University
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햲 — Fecal incontinence is defined as the repeated voluntary or
쏹 햽 — There is a lack of correlation between anatomic findings and
쏹 헆 — If the patient does not respond to therapy, further testing is
쏹
involuntary passage of feces in inappropriate places (e.g. under- the degree of fecal continence both in anorectal malformations and necessary. This may include a spinal MRI or anorectal manometry.
wear) after the age of 4 years. The most common form is the invol- neurogenic problems. Therefore, information on anorectal function A colonic transit study may exclude the presence of delayed transit,
untary leakage of stool, resulting in staining of the underwear. is necessary with the use of anorectal manometry. and aggressive behavioral evaluation and treatment may be neces-
sary.
햳 — Despite variations in the underlying pathophysiology, the
쏹 햾 — If a tethered cord is found, neurosurgical evaluation is neces-
쏹
goals of therapy are the same. These include social continence, sary. 쎻
쏹
21 — In patients with intractable incontinence, an ACE procedure
predictability, and eventually independence. should be considered. If it fails, the creation of a permanent colos-
햿 — If there is evidence that the initial repair was done outside the
쏹 tomy/ileostomy needs to be considered. In other patients with an
햴 — The initial step in the evaluation is to determine if there is an
쏹 muscle complex, a redo pull-through needs to be considered. How- imperforate anus who have megasigmoid and intractable symp-
organic problem. The most common reason for fecal incontinence ever, the patient needs to have evidence of good pelvic muscles. toms, resection of the rectosigmoid may be necessary.
is overflow incontinence from fecal retention. Incontinence also Medical therapy or other less complicated surgeries should be con-
occurs with malformations, trauma, surgery, or neurogenic prob- sidered before. 쎻
쏹
22 — For those patients who respond, the therapy needs to be
lems. continued. As the child grows older, and to achieve independence,
헀 — If the patient has low squeeze pressure and/or abnormal rec-
쏹 particularly when rectal interventions are being used, the ACE pro-
햵 — In otherwise healthy children, the presence of stool retention
쏹 tal sensation and the ability to understand commands, biofeedback cedure has been developed to produce a conduit or to place a but-
needs to be assessed. Fecal incontinence in the absence of stool is indicated. ton from the skin to the cecum that can be catheterized/accessed
retention is usually related to rapid transit, anorectal dysfunction, for the self-administration of enemas. This allows them to be pre-
neuropathy, or behavioral problems. 헁 — After the anatomic basis of the incontinence has been stud-
쏹 dictable and independent.
ied, the next step in the evaluation is to establish if there is stool re-
햶 — Common organic reasons for fecal incontinence include ana-
쏹 tention which could be producing overflow incontinence.
tomic malformations or neurogenic problems. Anorectal malforma- Selected reading
tions represent a common cause of organic fecal incontinence. 헂 — The size of the sigmoid is particularly important in children
쏹
after repair of anorectal malformations. A colonic motility study may Bischoff A, Levitt M, Pena A: Bowel management for the treat-
햷 — The most common cause of neuropathic bowel in children is
쏹 also be necessary. ment of pediatric fecal incontinence. Pediatr Surg Int 2009; 25:
myelodysplasia. Other less common causes include tethered cord, 1027–1042.
spinal trauma, tumors, and sacral agenesis. 헃 — Patients with nonretentive soiling respond to multimodal ther-
쏹 Burgers R, Benninga M: Functional nonretentive fecal inconti-
apy. Treatment needs to include support for the child and parents, a nence in children: a frustrating and long-lasting clinical entity.
햸 — Tethered cord is frequently associated with anorectal malfor-
쏹 nonaccusatory approach, and a toilet training program with a reward J Pediatr Gastroenterol Nutr 2009; 48(suppl 2):S98–S100.
mations or myelomeningocele or can occur in isolation. A spinal system. Laxatives, bulking agents, or even loperamide may be need- Di Lorenzo C, Benninga M: Pathophysiology of pediatric fecal
MRI is necessary for diagnosis. ed. incontinence. Gastroenterology 2004; 126:S33–S40.
Pensabene L, Nurko S: Management of fecal incontinence in
햹 — If there is no evidence of stool retention, the most likely di-
쏹 헄 — Some patients have incontinence that is not related to stool
쏹 children without functional fecal retention. Curr Treat Options
agnosis is nonretentive fecal incontinence. The Pediatric Rome III retention. They may have rapid colonic transit or diarrhea, or be select Gastroenterol 2004; 7: 381–390.
criteria for diagnosis include the following: once a week or more patients with absent continence mechanisms. Treatment requires an Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS,
for the preceding 12 weeks, in a child >4 years, a history of (1) def- aggressive bowel program. Since liquid stools usually leak out with- Staiano A, Walker LS: Childhood functional gastrointestinal
ecation into places and at times inappropriate to the social context, out the patient’s perception, stools should be made more solid with disorders: child/adolescent. Gastroenterology 2006; 130: 1527–
(2) in the absence of structural or inflammatory disease, and (3) in dietary fiber. Alternatively, some patients may have increased colonic 1537.
the absence of signs of fecal retention. motility and pass stool constantly. In these cases, the use of antimotil- Yardley IE, Pauniaho SL, Baillie CT, Turnock RR, Coldicutt P,
ity agents such as loperamide may be beneficial. Behavioral interven- Lamont GL, Kenny SE: After the honeymoon comes divorce:
햺 — The most common form of soiling is overflow incontinence
쏹 tions with daily sitting programs should be instituted. To achieve pre- long-term use of the antegrade continence enema procedure.
due to constipation. dictability, it may be necessary to use enemas and suppositories. At J Pediatr Surg 2009; 44: 1274–1276.
times, the use of continence enemas has proven very beneficial. Nurko S: Complications after gastrointestinal surgery. A medi-
햻 — The evaluation of children with anorectal malformations is
쏹 cal perspective; in Walker WA, et al (ed): Pediatric Gastrointes-
complex. An assessment of the anal opening, the state of pelvic 헅 — If there is fecal retention, the use of mild laxatives and behav-
쏹 tinal Disease, ed 4. Philadelphia, Decker, 2004, pp 2111–2138.
and anal muscles, and the position and state of the neoanus is nec- ioral intervention is effective. A combination of behavioral interven- Nurko S, Scott SM: Coexistence of constipation and inconti-
41 essary. A physical examination, and at times imaging techniques tions, oral laxatives, fiber, and rectal interventions is often success- nence in children and adults. Best Pract Res Clin Gastroenterol
like pelvic MRI, or electrical rectal stimulation may be needed. A ful. Management strategies that improve stool consistency may be 2011; 25: 29–41.
differentiation between poorly developed muscles and improper useful. It is generally better to use stimulant laxatives, although they
placement of the neorectum is usually possible. Testing also allows make the bowel movements less predictable. Regular toilet sitting
Kainan University
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Other motility disorders A. Siddiqui · O. Eshach Adiv · S. Nurko Fecal incontinence
Other motility disorders P.E. Hyman · T. Zangen Hirschsprung’s disease
Hirschsprung’s disease
42 Resection of the aganglionic segment
No stricture Stricture
Normal Hypotensive Abnormal Normal
Anal stenosis anal sphincter colonic colonic
motility motility
Botox
Response
Redo pull-through Stool softeners Myotomy Resection Amitriptyline Supportive bowel Resection Irrigations
Kainan University
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— HD is characterized by the absence of ganglion cells in
— There are three reasons for incontinence after pull-
— If ganglion cells are present in the rectal biopsy, a motility
the myenteric and submucosal plexuses, ascending from the through: damaged (hypotensive) anal sphincter (<5% of HD evaluation is the next step. Based on anorectal and colon ma-
internal anal sphincter proximally for a variable distance. The children), overflow incontinence or soft stool leaking around a nometry findings, 3 groups of obstructive pathophysiology
pathogenesis of HD involves an interruption of the normal de- fecal impaction (10% of HD children). Liquid escapes when the were identified: (1) Normal colon manometry associated with
velopment of the enteric nervous system during embryonic life. child relaxes the pelvic floor for just a moment to pass gas. fear of defecation and fecal retention due to pelvic floor dyssyn-
Genetic analysis is consistent with an autosomal-dominant in- Most commonly, frequent HAPCs propagate through the neo- ergia. This condition is identical to functional constipation in
heritance with incomplete penetrance for long-segment disease rectum to the anal sphincter (50% of HD children). Anorectal healthy children. Fear prevents relaxation of the pelvic floor, a
and an autosomal-recessive and multifactorial profile for short manometry will reveal the hypotensive anal sphincter. Anal necessity for defecation. (2) Hypertensive nonrelaxing anal
segment disease. HD has been reported in association with tri- sonography can confirm the diagnosis of anal sphincter injury. sphincter, also termed internal anal sphincter achalasia. A my-
somy 21, central hypoventilation syndrome and Waardenburg When anal sphincter pressure is normal, colon manometry will otomy is probably necessary. (3) Neuropathy proximal to the
syndrome. diagnose the patients with frequent HAPCs that propagate aganglionic segment. A neuropathic motility disorder proximal
through the neorectum. Treatment with amitriptyline, anticho- to the aganglionic colon is frequently associated with HD (10–
— Presenting symptoms include failure to pass meconium
linergics and loperamide decreases the number and improves 20%). Ganglion cells are present, but there is defective coordi-
in the neonatal period, constipation that responds poorly to the consistency of stool. In functional constipation with inconti- nation of contractions.
medical treatment, abdominal distention, poor feeding, subopti- nence, treatment includes education of the child and family,
mal weight gain, and ribbon-like stools or bouts of diarrhea and osmotic laxatives and behavioral modification.
fever associated with enterocolitis. Selected reading
— HD-associated enterocolitis causes episodes of fever, de-
— Rectal biopsy is the preferred means of diagnosis. In HD,
hydration, abdominal distention and diarrhea. HD may present Chumpitazi BP, Nurko S: Defecation disorders in children after
neuron cell bodies are not present after looking at 100 or more with enterocolitis or occur after surgical correction of the dis- surgery for Hirschsprung disease. J Pediatr Gastroenterol Nutr
cuts with adequate submucosa. Anorectal manometry may be ease, even in the absence of enterocolitis preoperatively. The 2011; 53: 75–79.
accurate in a few specialized centers, assessing the rectoanal etiology is not well understood, but colon dysmotility is a risk Dasgupta R, Langer JC: Evaluation and management of persis-
inhibitory reflex in response to rectal balloon distensions. Due factor for continuing enterocolitis. Children with total colon HD tent problems after surgery for Hirschsprung disease in a
to difficulties with pediatric instrumentation, dilated rectums are also at risk for enterocolitis. The risk for enterocolitis may be child. J Pediatr Gastroenterol Nutr 2008; 46: 13–19.
and movement artifacts, manometry is not as reliable as biopsy reduced by routine rectal irrigation or long-term administration Hyman PE: Defecation disorders after surgery for
in most centers. of MET or sulfasalasine. Acute episodes are managed with bow- Hirschsprung’s disease. J Pediatr Gastroenterol Nutr 2005;
el rest, i.v. fluid administration, bowel decompression, bowel 41(suppl 1):S62–S63.
— The current treatment for HD is surgical resection of the
irrigations and broad-spectrum antibiotics. Enterocolitis is the
aganglionic segment and restoration of bowel continuity bring- most common cause of death in children with HD, and aware-
ing the normal bowel down to the anus while preserving nor- ness of the family and the physicians to the symptoms is ex-
mal sphincter function. The most common surgeries are the tremely important.
Swenson, Soave and Duhamel procedures. These may be done
through the laparoscope with primary anastomosis or by lapa-
— Mechanical obstruction can result from stricture of surgi-
rotomy and a two-stage procedure. The outcomes of the surgi- cal anastomosis, retained aganglionic spur after Duhamel pro-
cal procedures appear to be comparable. cedure, that may fill with stool and obstruct the bowel. Physical
examination and a barium enema will help make the diagnosis.
— After surgery, a majority of those affected have chronic
Treatment includes stricture dilations, but some patients may
problems including delayed toilet training, persistent constipa- need a redo pull-through.
tion, fecal incontinence or enterocolitis. An individual child may
have a combination of these symptoms. — In the absence of mechanical obstruction, a rectal biopsy
is the next diagnostic procedure. It may reveal a rare retained
— Obstructive symptoms include abdominal distention,
aganglionic segment and then a redo pull-through is indicated.
bloating, vomiting or constipation. The etiology can be either
mechanical or functional obstruction.
43
Chronic intestinal pseudo-obstruction
44 Symptoms of intestinal obstruction
X-ray: dilated small/large bowel loops
Yes No No Yes
No Yes
Kainan University
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— CIP is a rare, disabling disorder characterized by repetitive
ated systemic or a metabolic disease is suspected, appropriate (TPN) or partial PN, one third require total or partial tube feeding,
episodes or continuous symptoms and signs of bowel obstruc- laboratory tests should be performed to identify a potentially and the rest eat by mouth. Every effort should be done to maxi-
tion, including radiographic documentation of dilated bowel with curable or treatable disease. mize enteral nutrition support in PN-dependent children. Continu-
air-fluid levels, in the absence of fixed, lumen-occluding lesions. ous feeding via gastrostomy or jejunostomy may be effective
The term CIP is applied to different conditions of congenital or ac- — When there is no obstruction at laparotomy, a full-thick-
when bolus feeds fail.
quired, transient, or permanent disorders of the enteric nerves, ness biopsy should be obtained for pathologic diagnosis. Tissue Prokinetic drugs have no role when the patient requires TPN but
muscles, or connective tissues that cause difficulties in transit, may be processed for routine histology, histochemistry for neu- may improve symptoms in patients who eat. Prucalopride, cis-
often resulting in intestinal failure. This heterogeneous group of rotransmitters and receptors, special stain for Cajal cells, electron apride, and tegaserod stimulate serotonin receptors and facilitate
disorders shares clinical features and treatments. microscopy for muscle disease, and silver stain for neuropathic acetylcholine release from the neuromuscular junction of intesti-
disease. Neurons in the submucous plexus of a rectal biopsy nal tissues, increasing the number and amplitude of contractions.
— CIP is a clinical diagnosis and depends on the recognition
eliminate the possibility of HD. Neuropathic findings may include Sequential intravenous erythromycin and octreotide may im-
of the clinical syndrome and the exclusion of mechanical obstruc- maturation arrest of the myenteric plexus with fewer neurons, prove gastric emptying and stimulate phase III of the migrating
tion. A few cases are diagnosed in utero by US findings of poly- which may be smaller than normal, inflammatory infiltrates in motor complex. Erythromycin binds to motilin receptors in the
hydramnios, megacystis, and abdominal distention. Intestinal the myenteric ganglia, or changes consistent with IND. However, gastric antrum, stimulating 3 gastric antral contractions per min-
malrotation is common. More than half of the affected children IND pathology correlates poorly with motility-related symptoms ute and induces phase III in patients capable of generating it. Oc-
present with symptoms of acute bowel obstruction within the and does not predict clinical outcome. Myopathic findings may treotide inhibits gastric emptying, gallbladder emptying, and
first hours of life. More than 75% present with symptoms of con- include thin muscularis in hollow visceral myopathy, extensive pancreatic secretion. The inhibition of gastric emptying is mitigat-
stipation or diarrhea, vomiting, and FTT in the first year of life. fibrosis in the muscle tissue by light microscopy, or vacuolar de- ed by pretreatment with erythromycin so combination therapy
The remainder present sporadically through the first two de- generation and disordered myofilaments by electron microscopy. may be beneficial. Bacterial overgrowth is a common complica-
cades. The clinical course is characterized by relative remissions tion of CIP. Most clinicians use 1- to 2-week rotating cycles of
and exacerbations. Factors that precipitate deteriorations include — In patients with chronic or recurrent symptoms of intesti-
broad-spectrum antibiotics such as AMO and clavulanic acid, co-
intercurrent infections, general anesthesia, psychological stress, nal obstruction, diagnostic testing provides information about trimoxazole, and MET often with antifungals such as nystatin or
and malnutrition. In children who previously had surgery, it can the nature and severity of the pathophysiology. Plain abdominal fluconazole, interspersed with antibiotic-free periods. Constipa-
be difficult to discriminate between physical obstruction related films may identify distended bowel loops. Scintigraphy demon- tion is treated with oral polyethylene glycol, suppositories, or en-
to adhesions and an episodic increase in symptoms. strates delayed gastric emptying of solids and liquids and reflux emas. Abdominal pain is common, and acute pain is best treated
of intestinal contents back into the stomach. Hydrogen breath by decompression of the distended bowel. Opiates are inadvis-
— Most congenital cases are both rare and sporadic. There is
testing reveals increased fasting breath hydrogen and a rapid in- able because they disorganize motility. Patients with chronic pain
no family history of pseudo-obstruction and no associated syn- crease in breath hydrogen with a carbohydrate meal as a marker benefit from a multidisciplinary approach that includes behavior-
drome. The disease is limited to the GI tract, and in 40–50% the for intestinal bacterial overgrowth. Intestinal manometry reveals al or relaxation therapy and the use of nonnarcotic medications.
urinary tract is affected as well. In some cases, familial inherited the pathophysiology responsible for the symptoms. In neuropa- Surgical procedures may be required to reduce symptoms and
autosomal-dominant and autosomal-recessive neuropathic and thy, undilated bowel has contractions of normal amplitude, but improve quality of life in patients with CIP on TPN. Gastrostomy
dominant and recessive myopathic inheritance patterns were they are uncoordinated. In myopathy, contractions are of persis- and jejunostomy are used for feeding and drug administration as
identified. In the autosomal-dominant diseases, expressivity and tently low amplitude, but coordinated. Testing should be per- well as a route for decompression of the stomach and small in-
penetrance are variable; some of those affected die in childhood, formed when the patient feels well and not in an acute episode of testine. Ileostomy decompresses the distal small intestine and
but those less affected are able to reproduce. In some congenital CIP that is usually associated with ileus and bowel dilation. Dilated removes the high-pressure zone of the anal sphincter. Failed
cases, there is evidence of predisposing factors such as intrauter- bowel may have no contractions, and thus studies of dilated bow- medical management may signal a need for total bowel resection
ine exposure to toxins (fetal alcohol syndrome, narcotics), infec- el are not helpful in discerning the physiology. Normal intestinal alone or in combination with small bowel transplantation. Out-
tions (EBV, CMV), ischemia, or autoimmune disease. manometry does not happen in CIP, so a normal intestinal ma- comes in children with CIP are similar to those in children under-
nometry suggests that the clinician should consider other diagno- going transplantation for SBS.
— Pseudo-obstruction can be related to associated systemic
ses. In most cases, manometric abnormalities correlate with the
disease. Some secondary CIP cases are caused by muscular dys- clinical severity of the disease. The absence of the migrating mo-
trophies (myotonic dystrophy, Duchenne muscular dystrophy), tor complex in antroduodenal manometry correlates with a re- Selected reading
mitochondrial myopathies, scleroderma and other connective quirement for TPN in children but not adults. Colonic manometry
tissue diseases, generalized dysautonomia, chromosome abnor- is abnormal in colonic CIP, whereas anorectal manometry is nor- Conor FL, Di Lorenzo C: Chronic intestinal pseudo-obstruction:
malities (e.g. Down syndrome), neurofibromatosis, MEN type IIB, mal in CIP. assessment and management. Gastroenterology 2006; 130:
or metabolic disease (hypothyroidism, diabetes). S29–S36.
45 — Treatment includes supportive care, i.e. nutritional sup-
Hyman PE, Thapar N: Chronic intestinal pseudo-obstruction; in
— Acquired pseudo-obstruction can be related to postisch-
port, medications, and surgery to decompress dilated bowel. Faure C, Di Lorenzo C, Thapar N (eds): Pediatric Neurogastro-
emic neuropathy, postviral neuropathy, severe IBD and autoim- Nutritional support is important to achieve normal growth and enterology. New York, Springer, 2013, pp 257–270.
mune inflammatory response (celiac disease, chronic enterocoli- development but is also important for GI function. Motility im-
Kainan University
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Other motility disorders T. Zangen · P.E. Hyman Chronic intestinal pseudo-obstruction
Other motility disorders E. Chiou · S. Misra · S. Nurko Irritable bowel syndrome
Irritable bowel syndrome
46
Kainan University
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— IBS, one of the most common pediatric FGIDs, is charac-
— Additional workup should be directed and specific. This
— Inconsistent results from studies of dietary interventions
terized by chronic abdominal pain or RAP and disturbed defeca- may include imaging studies (e.g. abdominal plain film, abdom- have likewise failed to support their empiric use in IBS. For
tion. The pathogenesis of IBS is still unclear, but a comprehen- inal US, contrast studies), blood tests (e.g. thyroid function symptoms related to constipation, supplemental psyllium husk
sive biopsychosocial model of illness based on the complex in- tests), stool examination (e.g. stool culture and parasite tests), fiber may help to decrease abdominal pain by softening the
terplay of genetic, physiological, and psychological (e.g. social or upper endoscopy and colonoscopy. In the absence of alarm stool and enhancing colonic transit. Probiotics are theorized to
support, stress) factors has been widely accepted. signs, there is no evidence to support the routine use of abdom- improve symptoms by restoring the microbial balance in the
inal US, endoscopy, or esophageal pH monitoring. gut, by enhancing the intestine’s mucosal barrier, or by altering
— The Rome III criteria were developed to positively diag-
the intestinal inflammatory response. The optimal formulation
nose FGIDs based on symptoms. IBS is no longer considered a — Once a diagnosis has been made, maintenance of a
and dosing of probiotics for IBS, however, are not well known.
diagnosis of exclusion, and treatment can be initiated without strong provider and patient/family relationship is fundamental. Lactose intolerance has also long been implicated as a possible
an extensive workup. The physician should provide reassurance that the positive di- factor in IBS. Lactase deficiency is unlikely in younger children,
agnosis of IBS is not a failure to identify an organic illness, vali- but a 2- to 3-week trial of lactose restriction for older children
Rome III criteria for IBS date the patient’s symptoms as real while explaining the patho- and adolescents with IBS is relatively benign and may be con-
• Abdominal discomfort or pain (at least once per week for physiology of visceral pain and the concept of the brain-gut sidered depending on the clinical history and presentation. The
2 months) associated with two or more of the following in axis, and offer frequent support. Success in treating patients recent use of a low FODMAP (fermentable oligo-, di-, monosac-
25% of the time: with IBS begins with the establishment of an effective patient- charides and polyols) diet has been shown to be successful in a
(a) Improvement with defecation physician relationship. The management should be multidisci- selected group of patients.
(b) Onset associated with change in frequency of stool plinary, and the major therapeutic approaches include psycho-
(c) Onset associated with change in form (appearance) of stool social, pharmacologic, and dietary interventions.
• No evidence of an inflammatory, anatomic, metabolic, or neo- Selected reading
plastic process that explains the subject’s symptoms. — Psychosocial interventions include CBT, guided imagery,
gut-directed hypnotherapy, and biofeedback. Consistent results Di Lorenzo C, Colletti RB, Lehmann HP, Boyle JT, Gerson WT,
— In addition, a detailed history and physical examination
supporting the benefit of CBT have been published. CBT is Hyams JS, Squires RH Jr, Walker LS, Kanda PT; AAP Subcom-
are essential for making a diagnosis. Supportive features in- based on the interactions between thoughts, feelings, and be- mittee; NASPGHAN Committee on Chronic Abdominal Pain:
clude a history of abnormal stool passage (straining, urgency, haviors, and the goals include the improvement of coping skills, Chronic abdominal pain in children: a technical report of the
or feeling of incomplete evacuation) or bloating and abdominal the identification of triggers, and the reduction of maladaptive American Academy of Pediatrics and the North American So-
distension. There may be a history of stressful events or infec- behaviors. Gut-directed hypnotherapy involves relaxation ciety for Pediatric Gastroenterology, Hepatology and Nutrition.
tious episodes associated with the onset of symptoms. A careful through guided imagery to produce a state of increased recep- J Pediatr Gastroenterol Nutr 2005; 40: 249–261.
psychosocial history and a complete physical examination are tiveness to gut-specific suggestions and ideas. Bursch B: Psychological/cognitive behavioral treatment of
critical to look for evidence of growth deceleration, delayed pu- childhood functional abdominal pain and irritable bowel syn-
berty, or abnormalities on abdominal or rectal examination. — There are currently little data to support the routine use
drome. J Pediatr Gastroenterol Nutr 2008; 47: 706–709.
of any pharmacologic agents as the first-line therapy. Antispas- Huertas-Ceballos AA, Logan S, Bennett C, Macarthur C: Di-
— Some laboratory screening tests may be considered. A
modics are used on an as-needed basis, but their long-term ef- etary interventions for recurrent abdominal pain (RAP) and
CBC can show evidence of chronic anemia and inflammation. fectiveness remains unclear. For patients with constipation, irritable bowel syndrome (IBS) in childhood. Cochrane Data-
An elevated sedimentation rate and CRP also suggest active but medications such as PEG 3350 or lubiprostone can be used. base Syst Rev 2009:CD003019.
nonspecific inflammation. Serological markers for celiac disease Loperamide has shown efficacy in improving symptoms of diar- Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS,
should be drawn (tissue transglutaminase IgA). Urinalysis can rhea in adults. Antidepressant medications such as tricyclic anti- Staiano A, Walker LS: Childhood functional gastrointestinal
reveal hematuria from nephrolithiasis or show evidence of a depressants and SSRIs have also had mixed results for IBS disorders: child/adolescent. Gastroenterology 2006; 130: 1527–
UTI. complaints in children and adolescents but may be needed in 1537.
some selected patients, particularly those with anxiety. 5HT4 Saps M, Di Lorenzo C: Pharmacotherapy for functional gastro-
— Although none of these alarm signs and symptoms has
agonists and 5HT3 antagonists have been successfully used in intestinal disorders in children. J Pediatr Gastroenterol Nutr
been validated as predictive of an underlying disease, they re- adults but are not currently available for children. Gabapentin 2009; 49:S101–S103.
main useful and their presence should prompt consideration for has also been successfully used as a pain modulator. Suares NC, Ford AC: Diagnosis and treatment of irritable bow-
additional workup. el syndrome. Discov Med 2011; 11: 425–433.
47
햲
Protein-losing enteropathy
48
Yes No
Establish presence of PLE and aim to diagnose specific cause 햴 Consider other nonintestinal causes of
hypoproteinemia 햳
Renal losses
Conduct thorough history and physical examination 햵 Impaired protein synthesis due to liver disease
Losses into body cavities or skin
Malnutrition
Consider laboratory studies 햶
Stool for į1-antitrypsin can confirm intestinal
(but not esophageal or gastric) protein losses
Consider further testing to target specific etiology
Celiac disease
50
Symptomatic 햲 Asymptomatic 햳
Chronic diarrhea Syndromes associated with celiac disease
Malabsorption Turner, Down, Williams
FTT Autoimmune diseases
Anemia PBC, diabetes mellitus type 1
Weight loss Autoimmune thyroiditis
Abdominal pain First-degree family relative of a person with celiac disease
Aphthous ulcers Osteopenia
Abnormal LFT
Laboratory evaluation 햴
TTGA 햶 DGPA 햷
EMA
DGPA
EMA and
HLA-DQ2/HLA-DQ8 positive
Patient symptomatic
Yes No
Diagnosis Small bowel biopsy Follow-up Small bowel biopsy Celiac disease is unlikely
51
Helicobacter pylori
Symptoms
52
CLA resistance? 햴
Yes Unknown No
PPI + AMO + MET PPI + AMO + MET or PPI + AMO + CLA or PPI + AMO + CLA
bismuth + AMO + MET or sequential therapy
H. pylori eradicated?
Yes No
Yes Unknown
H. pylori eradicated?
Adapted from Koletzko et al. [2011] Observe Consider other antibiotics, bismuth, quadruple therapy or higher dosage
53
Gastrointestinal polyps
54 Recurrent rectal bleeding 햲
GI polyp suspected 햳
Stable Unstable
Nonurgent referral for evaluation and endoscopy Urgent referral for endoscopy
햲
Intestinal malabsorption – Part 1 :
Pathogenesis and etiology
56
Bacteria Chymotrypsin Steatocrit Fecal-reducing Cellobiose/mannitol Fecal leukocytes Xylose oral load
Viruses į1-Antitrypsin Fecal elastase substances į1-Antitrypsin Calprotectin (serology for
3
Parasites Sweat test H-lactose Rectal nitric oxide celiac disease)
C. difficile toxins breath test Occlut blood Tests for food
Stool electrolytes Fecal lactoferrin allergy
14
C-D-xylose (prick/patch)
Breath test for small
intestinal bacterial
59
First-line investigations
Stool microscopy and culture
CBC, ESR, CRP and albumin
Consider fecal calprotectin
If findings (especially endoscopy and histology) confirm IBD, distinguish between CD and UC
Ileal or upper gut serpentine ulcers, Red flags not often seen with typical UC
stenosis or cobblestoning (not compatible Microscopic rectal sparing or microscopic skip lesions,
with backwash ileitis) or any inflammation extensive upper GI disease, poor growth, perianal skin tags
in other parts of the small bowel or even and extensive fissuring, deep inflammation
one granuloma remote from ruptured crypt
or perianal fistula or large inflamed skin tags
No Yes
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— Typical symptoms of CD include diarrhea, pain and
— Endoscopic features of IBD include aphthoid ulcers, ser-
Selected reading
weight loss, whereas UC most commonly presents with bloody piginous ulcers, increased friability, granularity and loss of nor-
diarrhea. However, children and adolescents may have atypical mal mucosal markings. Histologic features of IBD include active Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glick-
symptoms, such as short stature, arthritis, unexplained anemia chronic inflammation with granulomata, skip lesions and trans- man JN, Gold BD, Griffiths AM, Jevon GP, Higuchi LM, Hyams
or delayed puberty. Others may present with concerns of eating mural involvement in CD. JS, Kirschner BS, Kugathasan S, Baldassano RN, Russo PA:
disorder (anorexia nervosa) or present to surgeons (e.g. with Differentiating ulcerative colitis from Crohn disease in children
possible appendicitis or bowel obstruction). — Assessment of small bowel involvement should be un-
and young adults: report of a working group of the North
dertaken at the time of diagnosis regardless of the type of IBD. American Society for Pediatric Gastroenterology, Hepatology,
— Stools should be sent on 2–3 occasions for microscopy
Modalities may include CTE, MRI with small bowel protocol (i.e. and Nutrition and the Crohn’s and Colitis Foundation of Amer-
and culture. Microscopy for the presence of white cells on fresh MRE), contrast swallow or follow-through, contrast US Doppler ica. J Pediatr Gastroenterol Nutr 2007; 44: 653–674.
stools may indicate colitis. Standard bacterial pathogens as well or capsule endoscopy. These modalities along with white cell Bunn SK, Bisset WM, Main MJ, Gray ES, Olson S, Golden BE:
as Clostridium difficile, Aeromonas and Yersinia should be scanning may be considered in the situation of high clinical sus- Fecal calprotectin: validation as a noninvasive measure of
looked for. Consider Yersinia serology if clinical suspicion. picion but noncontributory endoscopy/histology. Of all modali- bowel inflammation in childhood inflammatory bowel disease.
ties, MRE should be preferred given its comparable accuracy to J Pediatr Gastroenterol Nutr 2001; 33: 14–22.
— CBC should be examined for hemoglobin (decreased with
that of CTE but without radiation; both MRE and CTE are more Dubinsky M: What is the role of serological markers in IBD?
blood loss or iron deficiency), red cell parameters (hematocrit, accurate than contrast follow-through. Pediatric and adult data. Dig Dis 2009; 27: 259–268.
MCV), platelets (increased as acute-phase response) and white IBD Working Group of the European Society for Paediatric
cells. ESR and CRP may be raised in gut inflammation, whereas
— Standard classification into CD or UC should be undertak-
Gastroenterology, Hepatology and Nutrition: Inflammatory
albumin may be reduced (negative acute-phase response and en. Colitis with some features of CD may be termed ‘IBD unclas- bowel disease in children and adolescents: recommendations
enteric protein loss). sified’. Other investigations may help to distinguish between for diagnosis – the Porto criteria. J Pediatr Gastroenterol Nutr
the two. 2005; 41: 1–7.
— Sensitivity and specificity of these blood tests are low. All
Lemberg DA, Clarkson CM, Bohane TD, Day AS: Role of
four blood tests may be within normal limits at diagnosis when — Backwash ileitis can be described as a short segment of
esophagogastroduodenoscopy in the initial assessment of
disease activity is mild (50% in UC and 20% in CD). mild, nonstenosing endoscopic ileitis without cobblestoning, children with inflammatory bowel disease. J Gastroenterol
serpentine ulcers or granulomatas histologically in the presence Hepatol 2005; 20: 1696–1700.
— If available, consider measurement of fecal calprotectin
of pancolitis. Levine A, Griffiths A, Markowitz J, Wilson DC, Turner D, Rus-
or lactoferrin as these noninvasive biomarkers have greater sen- sell RK, et al: Pediatric modification of the Montreal classifica-
sitivity and specificity for the detection of gut inflammation than — Various features can help to distinguish between UC and
tion for inflammatory bowel disease: the Paris classification.
blood markers. CD. In the presence of colitis, other features that exclude a diag- Inflamm Bowel Dis 2011; 17: 1314–1321.
nosis of UC include histologic rectal sparing, microscopic skip Mack DR, Langton C, Markowitz J, et al: Laboratory values for
— In children and adolescents, the initial endoscopic assess-
lesions, ulcerative or cobblestoning ileal disease, extensive up- children with newly diagnosed inflammatory bowel disease.
ment must include an upper endoscopy as well as an ileocolo- per GI tract disease and perianal changes (fistulas, atypical fis- Pediatrics 2007; 119: 1113–1119.
noscopy. Multiple biopsies should be obtained for histologic sures or extensive tags). Sidler MA, Leach ST, Day AS: Fecal S100A12 and fecal calpro-
assessment. Diagnosis and/or management may be changed if tectin as noninvasive markers for inflammatory bowel disease
gastroscopy is undertaken routinely.
— Serological markers against microbial antigens (such as
in children. Inflamm Bowel Dis 2008; 14: 359–366.
anti-Saccharomyces cerevisiae antibody) may play roles in diag- Turner D, Griffiths AM: Esophageal, gastric, and duodenal
nosing IBD, distinguishing between CD and UC in those with manifestations of IBD and the role of upper endoscopy in IBD
IBD unclassified and indicating long-term prognosis. Other anti- diagnosis. Curr Gastroenterol Rep 2007; 9: 475–478.
bodies include CBir, antiflagellin and the Glycominds panel (e.g.
ACCA and AMCA).
61
62
Maintenance therapy Induction therapy for active disease (PCDAI >10) points 햲
In selected Consider symptoms EEN for 8–12 weeks 5-ASA 햷 and/or Taper corti- Consider symptoms
high-risk due to stenosis, infection with elemental or ciprofloxacin with costeroids due to stenosis, infection
patients (e.g. C. difficile and CMV), polymeric formula 햶 or MET (2–4 weeks) 햸 over 8–10 (e.g. C. difficile and CMV),
wrong diagnosis, 12 weeks of budesonide (may be added weeks; start wrong diagnosis,
medication side effects (3–9 mg/day) to EEN) maintenance medication side effects
therapy
(see top left) In selected high-risk
Admit for i.v. children or those
Anti-TNF therapy Switch (i.e. MTX methylprednisolone with severe growth
after thiopurine or 1–1.5 mg/kg/day retardation or
vice versa) (up to 40–60 mg) clinically significant
in two divided doses 햹 fistulizing disease
Switch (i.e.
adalimumab
after infliximab Consider anti-TNF therapy
or vice versa) 햺
No therapy, Consider other treatments Within 3 months, stop budesonide, Taper corticosteroids Consider other
5-ASA or (e.g. off-label biologics, surgery) 햽 5-ASA, nutritional therapy and over 8–10 weeks, treatments
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햲 — The Pediatric Crohn’s Disease Activity Index (PCDAI) has
쏹 햷 — The 5-ASA treatment should consist of 70–80 mg/kg/day
쏹 Selected reading
been developed for the use in children. Cutoff values for remis- up to 4.8 g daily in two divided doses.
sion and mild, moderate and severe disease activity have been Cucchiara S, Escher JC, Hildebrand H, Amil-Dias J, Stronati L,
validated previously. 햸 — Blood tests and the presence of neuropathy should be
쏹 Ruemmele FM: Pediatric inflammatory bowel diseases and the
monitored when taking MET for a prolonged period of time. risk of lymphoma: should we revise our treatment strategies?
햳 — The addition of sulphasalazine to prednisone may have
쏹 J Pediatr Gastroenterol Nutr 2009; 48: 257–267.
advantages in colonic CD. 햹 — In severe selected cases, bowel rest and TPN may en-
쏹 Dubinsky MC, Reyes E, Ofman J, Chiou CF, Wade S, Sandborn
hance the remission rate. However, this modality should be WJ: A cost-effectiveness analysis of alternative disease man-
햴 — Doses of oral azathioprine should be 2–2.5 mg/kg once a
쏹 carefully considered because of the low tolerability of fasting in agement strategies in patients with Crohn’s disease treated
day and of 6-mercaptopurine it should be 1.5 mg/kg once a day. children. with azathioprine or 6-mercaptopurine. Am J Gastroenterol
Typical onset of action is within 3–4 months. CBC (initially once 2005; 100: 2239–2247.
a week) and liver enzymes (less frequently) should be moni- 햺 — In cases of primary anti-TNF failure (to differentiate from
쏹 Hyams JS, Ferry GD, Mandel FS, Gryboski JD, Kibort PM,
tored for cytopenia. Measurement of TPMT (genotyping or en- the primary response followed by a loss of response), the Kirschner BS, et al: Development and validation of a pediatric
zymatic activity) at baseline and measurement of 6-TG and switch to another anti-TNF regimen is associated with a low Crohn’s disease activity index. J Pediatr Gastroenterol Nutr
6-MMP levels after 2–3 months may aid in optimizing thiopurine success rate. 1991; 12: 439–447.
dosing but do not alleviate the need for frequent monitoring of Johnson T, Macdonald S, Hill SM, Thomas A, Murphy MS:
blood tests. 햻 — Although PEN has been shown to be significantly inferior
쏹 Treatment of active Crohn’s disease in children using partial
to EEN in inducing remission in CD, some weak evidence sug- enteral nutrition with liquid formula: a randomised controlled
햵 — The MTX dose should be 15 mg/BSA once a week. Sub-
쏹 gests that it may be partially effective in maintaining remission trial. Gut 2006; 55: 356–361.
cutaneous dosing is likely as effective as intramuscular dosing in pediatric CD. Turner D, Griffiths AM, Walters TD, Seah T, Markowitz J, Pfef-
but less painful. There are insufficient data to support oral treat- ferkorn M, et al: Appraisal of the pediatric Crohn’s disease ac-
ment. Daily folic acid should be prescribed to minimize adverse 햽 — Surgery is particularly attractive in children with refrac-
쏹
tivity index on four prospectively collected datasets: recom-
events. Liver enzymes and CBC should be monitored, initially tory short-segment ileal disease without colonic involvement mended cutoff values and clinimetric properties. Am J Gastro-
every 2 weeks. After 4 months, once remission is achieved (typi- and those with stenotic ileal disease unresponsive to anti-in- enterol 2010; 105: 2085–2092.
cal onset of action 2–3 months), the dose may be reduced by flammatory therapy. Ileal resection has been proved to acceler- Turner D, Grossman AB, Rosh J, Kugathasan S, Gilman AR,
40%. MTX has been shown to improve growth in thiopurine-re- ate growth in prepubertal growth retardation. Baldassano R, et al: Methotrexate following unsuccessful thio-
sistant children. purine therapy in pediatric Crohn’s disease. Am J Gastroenter-
햾 — Currently, monotherapy with biologics (i.e. without a con-
쏹
ol 2007; 102: 2804–2812.
햶 — EEN should be especially preferred in children with poor
쏹 comitant immunomodulatory agent) is recommended in low- Yamamoto T, Nakahigashi M, Saniabadi AR, Iwata T,
growth, low weight and catabolic state (e.g. hypoalbuminemia). risk children due to the associated risk for hepatosplenic T cell Maruyama Y, Umegae S, et al: Impacts of long-term enteral
lymphoma with dual therapy. However, concomitant thiopurine nutrition on clinical and endoscopic disease activities and mu-
may improve the 1-year remission rate. cosal cytokines during remission in patients with Crohn’s dis-
ease: a prospective study. Inflamm Bowel Dis 2007; 13: 1493–
1501.
63
Ulcerative colitis
64
Exacerbation Assessment of disease activity
Kainan University
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Medical therapies in IBD should be divided into those that in- — In clinical practice, a dose of up to 100 mg/kg is often
Selected reading
duce remission (5-ASA, corticosteroids, anti-TNF therapy, and used effectively but without solid evidence.
likely probiotics) and those that maintain remission (5-ASA, McGinnis JK, Murray KF: Infliximab for ulcerative colitis in
thiopurines, anti-TNF therapy, and likely probiotics). — In cases resistant to the newer 5-ASA regimes (e.g. Asa-
children and adolescents. J Clin Gastroenterol 2008; 42: 875–
col, Pentasa, Rafassal), it may be beneficial to switch to sul- 879.
— In any state of active disease, the following must be ruled
fasalazine that may be more effective but is also associated with Oussalah A, Laclotte C, Chevaux JB, Bensenane M, Babouri A,
out: infectious colitis and Clostridium difficile, 5-ASA-related a higher adverse event rate (e.g. hypersensitivity, headache, GI Serre AA, et al: Long-term outcome of adalimumab therapy
colitis, and wrong diagnosis (e.g. immune deficiency, chronic side effects, or azoospermia). A gradual dose increase over 7–14 for ulcerative colitis with intolerance or lost response to inflix-
granulomatous disease, or Behcet’s disease). days may decrease the adverse event rate. imab: a single-centre experience. Aliment Pharmacol Ther
2008; 28: 966–972.
— In children, endoscopic evaluation of the rectal mucosa is
— Measurement of TPMT (genotyping or enzymatic activity)
Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A,
conceived to be too invasive for repeated monitoring of disease at baseline and after 2–3 months also of 6-TG and 6-MMP levels Johanns J, et al: Infliximab for induction and maintenance
activity and response to therapy. Therefore, reliance on nonin- may aid in optimizing thiopurine dosing. therapy for ulcerative colitis. N Engl J Med 2005; 353: 2462–
vasive indirect markers of disease activity should be used at 2476.
most visits. The Pediatric UC activity index (PUCAI) was devel- — According to pediatric cohorts, PUCAI >45 points at day 3
Turner D, Hyams J, Markowitz J, Lerer T, Mack DR, Evans J, et
oped for the use in children and has proved to be highly corre- warrants preparation for second-line therapy (cyclosporine, al: Appraisal of the pediatric ulcerative colitis activity index
lated with the endoscopic appearance of the colonic mucosa. infliximab, or colectomy) and >65–70 points at day 5 warrants (PUCAI). Inflamm Bowel Dis 2009; 15: 1218–1223.
Cutoff values for remission and mild, moderate, and severe dis- execution of the planned therapy. Those children not meeting Turner D, Levine A, Escher JC, Griffiths AM, Russell RK, Dig-
ease activity have been previously validated in two independent these cutoff values may be slow responders and should be nass A, et al: Management of pediatric ulcerative colitis: joint
pediatric cohorts. Endoscopic evaluation of the colonic mucosa treated with corticosteroids for 2–5 more days until a decision ECCO and ESPGHAN evidence-based consensus guidelines. J
is indicated before major treatment changes, when the clinical is made. Pediatr Gastroenterol Nutr 2012; 55: 340–361.
presentation is in question and during acute severe exacerba- Turner D, Otley AR, Mack D, de Bruijne J, Uusoue K, Walter T,
tion not responding to intravenous steroid therapy. — Level 1 evidence for using biologics in pediatric UC is
et al: Development and evaluation of a Pediatric Ulcerative
currently available for infliximab in patients with moderate to Colitis Activity Index (PUCAI): a prospective multicenter study.
— Recent data in adults suggest that 3 g Pentasa once a day
severe disease but not in those hospitalized for acute severe Gastroenterology 2007; 133: 423–432.
is superior to a dose administered twice a day. colitis. Turner D, Travis SP, Griffiths AM, Ruemmele FM, Levine A,
Benchimol EI, et al: Consensus for managing acute severe ul-
— In high-risk patients (such as those presenting with se-
— Colectomy should also be considered in chronically ac-
cerative colitis in children: a systematic review and joint state-
vere colitis, especially at a young age), thiopurine may be con- tive, resistant disease and in cases of complications (e.g. toxic ment from ECCO, ESPGHAN, and the Porto IBD Working
sidered for maintenance therapy at onset. megacolon, dysplasia, or uncontrolled bleeding). Group of ESPGHAN. Am J Gastroenterol 2011; 106: 574–588.
Turner D, Walsh CM, Benchimol EI, Mann EH, Thomas KE,
Chow C, et al: Severe paediatric ulcerative colitis: incidence,
outcomes and optimal timing for second-line therapy. Gut
2008; 57: 331–338.
65
Abdominal mass
66
Radiological studies 햲
NB 햶 Nonrenal mass
Liver 햸
Ovary 햺
Abdominal lymphoma 햻
Rhabdomyosarcoma 햽
Inflammatory
Miscellaneous (intussusception) 햾
67
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햲 — Abdominal pain is divided into three categories: visceral
쏹 햷 — Certain drugs may cause abdominal pain. These include
쏹 햿 — Plain film abdominal radiographs are most useful in the
쏹
pain, parietal (somatic) pain, and referred pain. Visceral pain NSAIDs, salicylates, antibiotics (erythromycin), calcium channel detection of intestinal obstruction or perforation, appendiceal
occurs as a stimulation of visceral pain fibers by inflammation, blockers, lead poisoning, venoms, and some asthma medica- fecalith, and kidney stones. Chest radiographs may help rule out
ischemia, or stretching. Parietal pain arises from stimulation of tions. pneumonia. CT is likely more accurate than US in the diagnosis
the parietal peritoneum. Referred pain is felt in a body region of appendicitis, abscesses, CD, and kidney stones. US with
distant from the diseased organ and is supplied by the same 햸 — Children with appendicitis usually lie in bed, the legs may
쏹 graded compression is most useful in diagnosing gallstones,
dermatome. be drawn up flexed. A squirming, screaming child rarely has gynecologic pathology (such as ovarian cysts, ovarian torsion,
appendicitis. Children with visceral pain tend to writhe during etc.), or advanced periappendiceal inflammation.
햳 — In infants and preschool children, the most common
쏹 waves of peristalsis, while children with peritonitis remain quite
causes of RLQAP are infantile colic, gastroenteritis, constipa- still and resist movement. Parietal pain is well localized, sharp, 헀 — Indications for surgical consultations in children with
쏹
tion, UTI, intussusception, and incarcerated hernia. In school- intense, and aggravated by coughing or movement. The hydra- RLQAP include suspected surgical cause for the pain, RLQAP
age children, RLQAP may be a result of gastroenteritis, appendi- tion status of the child should be assessed. without an obvious etiology, significant abdominal trauma, bile-
citis, constipation, functional pain, or UTI. In adolescents, the stained or feculent vomiting, involuntary abdominal guarding/
most common causes are appendicitis, gastroenteritis, consti- 햹 — Fever indicates an underlying infection or inflammation.
쏹 rigidity, rebound tenderness, and signs of intra-abdominal fluid.
pation, dysmenorrheal pain, mittelschmerz, PID, and ovarian Most children with appendicitis have a low-grade fever of 37–
torsion. 38 ° C. High fever with chills is typical of perforated appendicitis,
pyelonephritis, and pneumonia. Tachycardia and hypotension Selected reading
햴 — Events that occur with a discrete, abrupt onset, such as
쏹 suggest hypovolemia. Shock in a postmenarcheal girl may sug-
the passage of a stone (biliary or renal), perforation of a viscus, gest ectopic pregnancy. Hypertension may be associated with Bishop WP: The digestive system; in Kliegman RM, Marcdante
or an infarction, result in a sudden onset of pain. The pain in HSP or HUS. Kussmaul’s respiration indicates diabetic ketoaci- KJ, Jenson HB, Behrman RE (eds): Nelson Essentials of Pediat-
appendicitis is continuous and usually occurs with the classic dosis. rics, ed 5. Philadelphia, Elsevier, 2006, pp 579–591.
sequence of shifting pain. Perforated appendicitis may result in Buchert GS: Abdominal pain in children: an emergency practi-
a temporary relief of the symptoms. Colic pain and relief of pain 햺 — Auscultation of the chest should be performed to exclude
쏹 tioner’s guide. Emerg Med Clin North Am 1989; 7: 497–517.
after a bowel movement suggest a colonic source. The relief of right lower lobe pneumonia, which can mimic appendicitis. In Caty MG, Azizkhan RG: Acute surgical conditions of the abdo-
pain after vomiting suggests a source in the more proximal the acute surgical abdomen, bowel sounds are diminished or men. Pediatr Ann 1994; 23: 192–201.
bowel. Previous episodes of similar pain point toward a sickle absent, while hyperperistalsis is frequent in gastroenteritis. Lo- Finelli L: Evaluation of the child with acute abdominal pain.
cell crisis or IBD. calized tenderness is essential in appendicitis, while the pres- J Pediatr Health Care 1991; 5: 251–256.
ence of guarding and rebound tenderness indicates localized Kulik DM, Uleryk EM, Maguire JL: Does this child have appen-
햵 — In the acute surgical abdomen, pain generally precedes
쏹 peritonitis. Deeper palpation is necessary to discover an or- dicitis? A systematic review of clinical prediction rules for chil-
vomiting, and the reverse is true in gastroenteritis. Any child ganomegaly or a mass, which may suggest intussusception or a dren with acute abdominal pain. J Clin Epidemiol 2013; 66: 95–
presenting with colicky pain, bilious vomiting, and failure to periappendicular abscess. 104.
pass flatus or feces should be presumed to have a bowel ob- Leung A, Sigalet DL: Acute abdominal pain in children. Am
struction. Diarrhea is often associated with gastroenteritis or 햻 — Rovsing’s sign (pressure on the left lower quadrant re-
쏹 Fam Physician 2003; 67: 2321–2326.
food poisoning; however, it may occur in perforated appendici- sults in RLQAP) is positive in appendicitis. A positive iliopsoas Mason JD: The evaluation of acute abdominal pain in children.
tis. Bloody diarrhea is much more suggestive of IBD or infec- test (passive extension of the right hip and flexion of the right Emerg Med Clin North Am 1996; 14: 629–643.
tious enterocolitis. The classic ‘currant-jelly stool’ is often seen thigh against resistance) or obturator test (rotation of the right Michalowski W, Rubin S, Slowinski R, Wilk S: Triage of the
in patients with intussusception. Fever indicates any inflamma- flexed hip) suggests an inflamed retrocecal or pelvic appendix. child with abdominal pain: a clinical algorithm for emergency
tory process (gastroenteritis, appendicitis, mesenteric lymphad- Jaundice suggests hemolysis or liver disease, and pallor and patient management. Paediatr Child Health 2001; 6: 23–28.
enitis, etc.). Loss of appetite or anorexia is common in appendi- jaundice point to sickle cell crisis. Phillips GS, Parisi MT, Chew FS: Imaging diagnosis of right
citis and is followed by the onset of nausea and vomiting. Dys- lower quadrant pain in children. AJR Am J Roentgenol 2011;
uria, urinary frequency, and malodorous urine suggest UTI, 햽 — The routine use of rectal examination in appendicitis is
쏹 196:W527–W534.
while cough, dyspnea, and chest pain point to a thoracic source. controversial. A rectal examination may provide useful informa- Schwartz MZ, Bulas D: Acute abdomen. Laboratory evaluation
Polyuria and polydipsia suggest diabetes mellitus. tion for the presence of masses, stool, and blood. In teenage and imaging. Semin Pediatr Surg 1997; 6: 65–73.
girls, purulent cervical discharge, cervical motion tenderness,
햶 — A careful menstrual cycle history as well as a history of
쏹 and adnexal masses are signs of PID.
sexual activity and contraception often yield important diagnos-
69 tic clues in teenage girls. Bilateral lower pelvic abdominal pain, 햾 — Elevated CBC (shift to the left), CRP, and ESR indicate any
쏹
a history of multiple sexual partners, and the use of contracep- inflammatory process, while elevated AST, ALT, GGT, and bili-
tives are often indicative of PID. Sudden colicky pain may sug- rubin levels suggest a biliary or liver disease. Abnormal urinaly-
gest torsion of either a normal ovary or an ovarian cyst. A sud- sis points to a UTI, stones, or glomerulonephritis. A positive
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Surgical conditions I. Sukhotnik · P.S. Lemos Right lower quadrant abdominal pain
Surgical conditions S. Peleg · R. Shaoul Peritonitis
Peritonitis
70 History 햲
Age (antenatal, neonatal, children)
Symptoms (poor feeding, lethargy, restlessness, nausea, vomiting, abdominal pain, diarrhea)
Signs (fever, abdominal distension and rigidity, diffuse rebound tenderness, pigmentation of
abdominal wall, paucity of body motion, decreased or absent bowel sounds, toxic appearance)
Specific questions about nephrotic syndrome, cirrhosis, causes of secondary peritonitis
Etiology 햳
Primary peritonitis
Secondary peritonitis
PMN count <250/mm3 PMN count PMN count >500/mm3 PMN count >250/mm3
250–500/mm3 Usually pH <7.35, Ascitic fluid bile stained
Yes No
arterial-ascitic fluid pH
No If bacterial culture is Intravenous antibiotics gradient >0.1, and
elevated lactate Ascitic fluid bilirubin Is there free air or extravagation Are there more PMN
treatment positive, symptoms if clinical suspicion
>60 mg/l and of contrast medium on the after 48 h of therapy
and signs of infection, high or wait and retap
ascitic fluid/serum abdominal imaging study? with antibiotics than
retap on day 3 within 48 h 햶
bilirubin >1 at baseline?
PMN count PMN count PMN count Culture Culture Yes No Yes
>250/mm3 <250/mm3 <250/mm3 negative positive
Second Second Biliary Perforation peritonitis Nonperforation Spontaneous
culture culture
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Is there evidence for
localized infection?
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Surgical conditions S. Peleg · R. Shaoul Peritonitis
Surgical conditions Y. Finkel · I. Sukhotnik Short bowel syndrome
ȞȞabsorptive ȞȞabsorptive Long-term TPN, Catheter-related Colonic dysbacteriosis Nonabsorbed fat binds
surface area surface area excessive glucose intake sepsis (Gram- Impaired metabolism luminal calcium
Osmotic diarrhea Impaired enterohepatic Increased ω6/ω3 LCFA positive and -negative) of D-lactate Lack of free calcium
due to metabolized circulation Impaired enterohepatic Gut bacterial to combine with lumen
disaccharide in colon Gastric hypersecretion circulation overgrowth (Gram- oxalate
ȞȞcolonic absorption Relative pancreatic Bacterial translocation negative, anaerobes) Increased colonic
due to bile salts and fatty insufficiency and portal endotoxemia oxalate absorption
acids Bacterial overgrowth Catheter-related sepsis Hyperoxaluria
Rapid transit Rapid transit Prematurity
Loss of ileocecal valve Diseased residual bowel Aluminium, iron, or
chromium overload
Diarrhea Steatorrhea Major problem around Sepsis Severe acidosis Oxalate nephrolithiasis Transient
Dehydration Diminished energy supply the 6th month Septic shock Impaired consciousness Renal colic pseudo-
Electrolyte malabsorption LCFA deficiency Impaired LFT Lactic acidosis Coma Hydronephrosis obstruction
B12 and iron deficiency Fat-soluble vitamin Ȝbilirubin and ammonia Short gut colitis Disaccharide
Bile salt deficiency malabsorption levels Ȝbacterial content by intolerance
Microelements deficiency End-stage liver failure small gut aspiration Short gut colitis
FTT Ȝfasting breath Ileocolic anasto-
hydrogen levels motic ulceration
Cholelithiasis
Phase 1: Immediate postoperative period Stimulating Broad-spectrum antibiotics Oral broad-spectrum antibiotics Low oxalate diet
Phase 2: Introduction of enteral nutrition enterobiliary axis for septic episode Probiotic agents Preventing dehydration
Phase 3: Advancing enteral nutrition (enteral feeding) Intermittent antibiotics (first Decreasing steatorrhea
Suppressing gut 5 days of each month) Increasing dietary calcium
Aims bacterial overgrowth Continuous cyclical antibiotics
Maintenance of fluid and electrolyte balance Ursodeoxycholic acid (oral MET)
Maintenance of growth and development (30 mg/kg/day) Prevention of colonic stasis
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— The functional definition of SBS presently used for epide-
Workup Selected reading
miological studies in children is a need for PN for more than 28 • History and physical examination
days. A different functional definition is based on measuring the • Search for other sources of fever (e.g. pneumonia, otitis, URI, D’Antiga L, Goulet O: Intestinal failure in children: the Europe-
fecal energy loss of patients with SBS, and a biological criteria meningitis, wound) an view. J Pediatr Gastroenterol Nutr 2013; 56: 118–126.
for defining intestinal failure was suggested by the measure- • CVC blood culture, from each port if double/triple lumen Goulet O, Colomb-Jung V, Joly F: Role of the colon in short
ment of citrulline as the marker of small intestinal epithelial • Peripheral blood culture (minimum 1 ml/bottle) bowel syndrome and intestinal transplantation. J Pediatr
masses. The functional consequences of SBS depend on (a) the • CBC with differential, platelet count Gastroenterol Nutr 2009; 48(suppl 2):S66–S71.
length, surface, and site of the resected small intestine, (b) the • Culture and Gram stain of CVC exit site if inflamed Goulet O, Ruemmele F: Causes and management of intestinal
functional capacity of the remaining intestine, and (c) the age of • Chest X-ray failure in children. Gastroenterology 2006; 130(2 suppl 1):S16–
the patient at the time at which the surgery was performed. • Urinalysis and urine culture S28.
Gupte GL, Beath SV, Kelly DA, Millar AJ, Booth IW: Current
— The etiologies of intestinal failure can be classified ac-
— Intestinal luminal bacteria produce both D- and L-lactate,
issues in the management of intestinal failure. Arch Dis Child
cording to inflammation, surgical reduction of the gut, SBS, but only L-lactate is well metabolized by most humans. When 2006; 91: 259–264.
neuromuscular disease involving the GI tract, and congenital malabsorbed, carbohydrates are broken down to D-lactic acid by Hodge D, Puntis JW: Diagnosis, prevention, and management
diseases of the intestinal epithelium. the bacteria it accumulates in the bloodstream and can result in of catheter related bloodstream infection during long term
diffusion of severe neurologic symptoms, even frank coma. parenteral nutrition. Arch Dis Child Fetal Neonatal Ed 2002;
— During the first stage after intestinal resection, there are
87:F21–F24.
large fluid and electrolyte losses, both from gastric fluid and os- — In case of steatorrhea, LCFA combine with magnesium
Kaufman SS, Loseke CA, Lupo JV, Young RJ, Murray ND,
tomy losses. During this stage, parenteral fluid and nutrition and calcium, making calcium unavailable for the formation of Pinch LW, Vanderhoof JA: Influence of bacterial overgrowth
therapy is mandatory aiming at an adequate metabolic support calcium oxalate. Unabsorbed bile salts in the colon increase the and intestinal inflammation on duration of parenteral nutrition
and prevention of complications. Separate prescriptions for PN mucosal permeability to oxalate. An increase in enteric oxalate in children with short bowel syndrome. J Pediatr 1997; 131:
and fluid replacements are important. absorption results in an increase in the risk of oxalate renal 356–361.
stones. Dietary oxalate restriction and oral calcium supplemen- Köglmeier J, Day C, Puntis JW: Clinical outcome in patients
— At the initial stage of feeding, it is customary to use
tation may help in the prevention of calcium oxalate renal from a single region who were dependent on parenteral nutri-
mother’s milk or a protein hydrolysate formula that is lactose stones. tion for 28 days or more. Arch Dis Child 2008; 93: 300–302.
free and may include MCT in order to facilitate absorption. Lee SI, Valim C, Johnston P, Le HD, Meisel J, Arsenault DA,
Small bowel bacterial overgrowth is a frequent complication — Gallstones occur by precipitation of cholesterol. This may
Gura KM, Puder M: Impact of fish oil-based lipid emulsion on
that causes mucosal inflammation and nutrient malabsorption be due to the low concentration of bile salts in the bile, which serum triglyceride, bilirubin, and albumin levels in children
by deconjugation of bile salts, which results in a depleted bile depends on the impaired enterohepatic circulation of bile acids. with parenteral nutrition-associated liver disease. Pediatr Res
salt pool and impaired micellar solubilization leading to steator- 2009; 66: 698–703.
rhea and malabsorption of fat-soluble vitamins.
— The management of SBS varies according to anatomi- Puder M: Infant parenteral nutrition-associated cholestasis: a
cal factors including the remaining small bowel length and the severe iatrogenic disease. JPEN J Parenter Enteral Nutr 2010;
— The etiology of IFALD is multifactorial, and known risk
preservation of the ileum, ileocecal valve, and colon. 34: 94–95.
factors include prematurity, low birth weight, duration of PN, In patients with dilated, poorly motile segments of the small
lack of enteral feeding, sepsis, multiple surgical procedures, and bowel (gastroschisis, atresia, NEC), reducing bowel dilatation
a diagnosis of jejunal atresia or gastroschisis. and small intestinal bacterial overgrowth have priority over ad-
vancing the volumes of enteral nutrition in order to reduce the
— Sepsis is a common complication of PN therapy in intesti-
risk of liver complications.
nal failure and SBS. Bacteria can spread by the central line exit Use tailored PN and deliver cyclical infusion as soon as toler-
site or hub or by bacterial translocation across the intestinal ance permits. Early oral feeding with breast milk should be pro-
wall. moted for newborns and infants. Continuous enteral feeding
should be used when necessary while balancing the advantages
of advancing enteral nutrition volumes to tube feeding-induced
feeding problems.
73
Neonatal jaundice
74
Physiological Congenital Diagnosis of Abnormalities NSC Metabolic Endocrine Inspissated Choledochal Bile duct PFIC BA
jaundice infections exclusion of bile acid disease disease bile malformation paucity syndromes Idiopathic
Hemolysis Multifactorial – metabolism
Galactosemia Hypopituitarism Alagille, neonatal
Breast milk sepsis, Tyrosinemia
Hypothyroidism nonsyndromic hepatitis
jaundice prematurity, CF į1-Antitrypsin
Gilbert’s syndrome hypoxia, Lysosomal deficiency
Crigler-Najjar syndrome PN storage disease NSC
types 1 and 2 Peroxisomal
disease
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Liver E. Fitzpatrick · A. Dhawan Neonatal jaundice
Liver Y. Bujanover · S. Reif Acute hepatitis
Acute hepatitis
76
Indications for testing
New onset of symptoms (nausea, jaundice, fever, anorexia, dark urine) 햲
Consider coinfection with HDV 햳 Order hepatitis panel including the following 햴
HAV antibody, IgM
HBC antibody, IgM
HBsAg
HCV antibody by CIA
Consider hepatitis E in endemic areas 햵
HAV antibodies+ HBC IgM antibodies+ HCV antibodies+ Negative hepatitis results
HBsAg+
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햲 — New onset of jaundice, fever, abdominal pain, nausea,
쏹 HCV – RNA flaviviridae virus. There are six genotypes with sev- Selected reading
vomiting, anorexia and dark urine are the typical symptoms of eral subtypes involved in hepatitis C. The route of infection is
acute hepatitis. The first laboratory study that confirms the diag- parenteral. Risk factors include receiving blood and tissue prod- Daniels D, Grytdal S, Wasley A: Surveillance for acute hepati-
nosis of hepatitis is the measurement of the transaminase blood ucts, intravenous drug use, organ transplantation, perinatal tis – United States, 2007. MMWR Surveill Summ 2009; 58: 1–27.
level. transmission and sexual activity. The incubation period is 20– Hochman JA, Balistreri WA: Acute and chronic viral hepatitis;
120 days. Most patients are asymptomatic, and only about 25% in Suchy FJ, Sokol RJ, Balistreri WF (eds): Liver Disease in
햳 — Hepatitis D occurs as a superinfection with hepatitis B.
쏹 of the infected subjects will develop jaundice. Transaminase Children. New York, Cambridge University Press, 2007, pp
Determination of serum IgM antibody against HDV will confirm levels are frequently fluctuating. The laboratory evaluation 369–446.
the diagnosis. should initially include the detection of antibodies to HCV using White FV, Dehner LP: Viral diseases of the liver in children:
CIA or ELISA. If those are low positive, RIBA should be per- diagnostic and differential diagnostic considerations. Pediatr
햴 — The main task of the laboratory workup of acute hepatitis
쏹 formed. Following a positive assay, a quantitative HCV RNA Dev Pathol 2004; 7: 552–567.
is to diagnose a disease caused by HAV, HBV and HCV. It is im- PCR test should be performed. Yeung LT, Roberts EA: Current issue in the management of
portant to rule out a chronic disease and to try to find another It is of importance to note that HAV, HBV and HCV can present paediatric viral hepatitis. Liver Int 2009; 30: 5–18.
individual that the patient has been in contact with who has or initially with fulminant hepatitis.
had the disease prior to the commencement of the symptoms in
the individual to be evaluated. 햵 — The course of hepatitis E resembles that of hepatitis A.
쏹
HAV – RNA picornavirus. Hepatitis A is more common among It occurs mainly in developing countries. The detection of anti-
day-care children and schoolchildren as well as in endemic ar- HEV IgG and IgM antibodies confirms the specific diagnosis.
eas. The route of infection is fecal oral. The main risk factors for
hepatitis A are day-care settings and contaminated food or wa- 햶 — In cases where hepatitis A, B, C, D or E has been ruled
쏹
ter. The investigator should always inquire about the history of out, consider another etiology of the disease. The differential
vaccination of the child. The incubation period is 15–50 days, diagnosis of acute hepatitis includes:
and the patient might be asymptomatic when first evaluated. A Infectious agents
positive test of anti-HAV IgM antibody will confirm the diagno- • Viral: CMV, EBV, HSV, HSV6, varicella-zoster virus, parvovirus
sis of acute hepatitis A. Negative IgM but positive IgG antibod- • Bacterial: Brucella, Leptospira, Rickettsia, tuberculosis
ies are indicative of an earlier infection or vaccination. • Parasitic: nematodes, toxocara
HBV – DNA hepadnavirus. The routes of infection include paren- Autoimmune diseases: AIH, AIC, systemic lupus erythematosus,
teral or perinatal transmission, infected household person and sarcoidosis
sexual contact. The incubation period is 2 weeks to 6 months. In Metabolic diseases: Wilson’s disease, CF, A1AT Def, hemochro-
addition to the symptoms described above, skin and joint symp- matosis
toms may accompany the acute presentation. Mild cases are Drugs: Acetaminophen, sulfonamides, antibiotics, antiepileptic
asymptomatic and detectable only by an increase in serum drugs
transaminase. The determination of serum HBsAg and anti-HBC Toxins: Carbon tetrachloride, alcohol
IgM will confirm the diagnosis of acute hepatitis B. However,
it is possible to detect HBC IgM antibodies in the absence of
HBsAg in the early stage, also called the window phase. The
presence of HBeAg represents infectiousness.
77
Hepatitis B
78
Prevention Transmission
1 dose of hepatitis B immunoglobulins
(for infants of HBsAg-positive mothers)
1st vaccine dose within 12 h of delivery Vertical/perinatal Blood products
Completion of 2nd and 3rd doses of The majority of cases Infection from HBsAg-positive
hepatitis B vaccine by 6 months 햲 household contacts
~90% 25–50%
20–30% 햷
Reactivation phase
HBeAg– chronic hepatitis B 햸
HBsAg+, HBeAg remains negative, anti-HBe+/–
DNA levels increase
ALT normal to elevated
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햲 — Infants born to HBsAg-positive mothers should be tested
쏹 햶 — Most children will eventually have undetectable HBeAg
쏹 Selected reading
for HBsAg and anti-hepatitis B antibodies at 12–18 months in and develop antibodies to HBeAg (anti-HBe). This is expected to
order to determine if infection has been prevented. occur in childhood or early adulthood, except for infection with Chen CJ, Iloeje UH, Yang HI: Long-term outcomes in hepatitis
genotype C (commonly observed in Asia), in which case the B: the REVEAL-HBV study. Clin Liver Dis 2007; 11: 797–816.
햳 — Chronic infection develops in up to 50% of young (1–5
쏹 mean age of HBeAg clearance is in the 4th to 5th decade. The D’Antiga AW, Atkins M, Moorat A, Vergani D, Mieli-Vergani G:
years old) acutely infected children, whereas only 5–10% of majority of children undergoing spontaneous HBeAg serocon- Combined lamivudine/interferon-alpha treatment in immuno-
acutely infected adolescents and adults have chronic infection. version (from the immune-tolerant phase to the inactive carrier tolerant children perinatally infected with hepatitis B: a pilot
state) will have a stage during which they manifest a biochemi- study. J Pediatr 2006; 148: 228–233.
햴 — During the immune-active phase, high HBV DNA levels
쏹 cally and histologically active disease. Identifying these children European Association for the Study of the Liver: EASL Clinical
and elevated ALT levels are associated with a greater risk of cir- and differentiating them from those children who are in a pro- Practice Guidelines: Management of chronic hepatitis B virus
rhosis and hepatocellular carcinoma. There is no strict linkage longed immune-active phase may be difficult. If an active phase infection. J Hepatol 2012; 57: 167–185.
between ALT levels and progression of liver disease. is observed for more than 6–12 months, the child should be Haber BA, Block JM, Jonas M, Karpen SJ, London WT, McMa-
treated. hon BJ, Murray KF, et al: Recommendations for screening,
햵 — In children, treatment is indicated during a prolonged im-
쏹 monitoring, and referral of pediatric chronic hepatitis B. Pedi-
mune-active phase or if they have HBeAg-negative chronic hep- 햷 — Most children who undergo HBeAg seroconversion will
쏹 atrics 2009; 124: 1007–1013.
atitis B in order to prevent progression of liver damage and de- remain in the inactive carrier state for years to decades. It is es- Jonas MM, Block JM, Haber BA, Karpen SJ, London WT, Mur-
crease the children’s risk of developing cirrhosis or hepatocellu- timated that 20–30% of children in the inactive carrier state will ray KF, et al: Treatment of children with chronic hepatitis B vi-
lar carcinoma. An enhanced response rate to IFN therapy has undergo reactivation of infection (HBeAg-negative chronic hep- rus infection in the United States: patient selection and thera-
been suggested in children aged 5 years or younger. Currently, atitis B). Yet, some children who are in the immune-tolerant peutic options. Hepatology 2010; 52: 2192–2205.
FDA-approved treatment regimens are IFN-α 5 MU/m2 s.c. thrice phase or the immune-active phase can also develop HBeAg- Kobar GE, MacKenzie T, Sokol RJ, Narkewicz MR: Interferon
weekly or IFN combined with lamivudine 3 mg/kg/day p.o. over negative chronic hepatitis B – they will move directly into this treatment for chronic hepatitis B: enhanced response in chil-
a 6- to 12-month period. IFN-α is approved for the use in chil- phase without first going into an inactive carrier phase. dren 5 years old or younger. J Pediatr 2004; 145: 340–345.
dren as young as 12 months of age, and lamivudine may be Shneider BL, Gonzalez-Peralta R, Roberts EA: Controversies in
used starting at 3 years of age. Lamivudine monotherapy 햸 — The follow-up of children with chronic hepatitis B in-
쏹 the management of pediatric liver disease: hepatitis B, C and
should be avoided because of the high rate of resistance ob- cludes the following: NAFLD: summary of a single topic conference. Hepatology
served (up to 64% over a 36-month period). There are currently • In infants who are HBeAg-positive with normal ALT levels, 2006; 44: 1344–1354.
no studies regarding the use of pegylated IFN in children with ALT levels as well as the HBeAg/anti-HBe status should be Sokal EM, Kelly DA, Mizerski J, Badia IB, Areias JA, Schwarz
chronic hepatitis B. monitored every 6–12 months. Routine monitoring of HBV KB, Vegnente A, et al: Long-term lamivudine therapy for chil-
Although the treatment of children who are in the immune-tol- DNA levels is not recommended. AFP should be measured at dren with HBeAg-positive chronic hepatitis B. Hepatology
erant phase of the disease is considered to be ineffective, a nov- baseline and once every 2–3 years until adolescence (there are 2006; 43: 225–232.
el approach to the treatment of patients at this stage of the dis- no specific guidelines).
ease has recently been suggested. In a pilot study utilizing se- • In infants and children with elevated ALT levels, these should
quential and combination therapy with lamivudine and IFN, a be monitored every 3 months. Treatment should be consid-
significant number of children underwent both HBeAg and ered if ALT and HBV DNA levels are elevated for a prolonged
HBsAg seroconversion. period of time (>6–12 months) or if HBeAg is negative and
HBV DNA levels are detectable.
79
Hepatitis C
80 Transmission
Prevention Vertical – from infected mother to infant; currently constitutes the major mode of infection; Horizontal – acquired through
Mode of delivery (cesarean section): occurs in ~6% of pregnancies blood transfusion or blood products
no definitive recommendations 햲 Factors associated with risk of infection
Breast feeding: supported Female gender
Maternal coinfection with HIV
High maternal viral load (HCV RNA >106 copies/ml)
Spontaneous clearance of vertically Generally benign with insidious, slow progression over 10–15 years: Generally mild, asymptomatic infection,
acquired infection in up to 20% of cases, ~50% asymptomatic which rarely may proceed to
mostly during the first 5 years 햴 ~30% have evidence of chronic active inflammation decompensated liver disease
(progression to cirrhosis is rare) 햵
Follow-up
Treatment
FDA-approved regimens 햶
IFN į-2b (3–5 MU/m2) 3 times weekly s.c. + ribavirin (15 mg/kg/day) p.o.
pegIFN į-2b (1.5 µg/kg) once weekly s.c. + ribavirin (15 mg/kg/day) p.o.
Both regimens for 24 weeks if genotype 2 or 3, or for 48 weeks if genotype 1 or 4
Adverse effects
Who should be treated? IFN/pegIFN – fever, flu-like symptoms, headache, anorexia, neutropenia, depression, alpecia, thyroid antibodies
Children >5 years of age Ribavirin – hemolytic anemia 햷, nausea, rash, cough
(younger children may clear
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햲 — Although cesarean section is not proven to have an ad-
쏹 햶 — Results of IFN monotherapy are poor, achieving an SVR
쏹 Selected reading
vantage in preventing transmission of infection, rupture of of 27% for genotype 1 and of 70% for nongenotype 1 (19 trials
membranes >6 h, internal fetal monitoring and intrapartum per- which included 366 children) and are thus not recommended. Bortolotti F, Verucchi G, Camma C, Cabibbo G, Zancan L, In-
ineal or vaginal lacerations have been reported to be associated By 2008, there were two FDA-approved treatments: IFN + ribavi- dolfi G, Giacchino R, et al: Long-term course of chronic hepati-
with higher transmission rates. rin is approved for children above the age of 3 years and the tis C in children: from viral clearance to end-stage liver dis-
pegylated IFN + ribavirin regimen is approved for children aged ease. Gastroenterology 2008; 134: 1900–1907.
햳 — In selected cases, if early confirmation or exclusion of in-
쏹 5 years and older. IFN in combination with ribavirin for 48 Chen ST, Ni YH, Chen PJ, Jeng YM, Lu MY, Wu JF, Hsu HY:
fection is needed, perform HCV PCR (HCV PCR has low sensitiv- weeks results in an SVR of around 40% in vertically infected Low viremia at enrollment in children with chronic hepatitis C
ity below the age of 1 month). genotype 1 patients, with both pretreatment normal or elevated favors spontaneous viral clearance. J Viral Hepat 2009; 16: 796–
serum aminotransferase levels. With pegylated IFNα-2a (180 µg 801.
햴 — Low HCV RNA levels, defined as <4.5 × 104 IU/ml, have
쏹 × BSA m2/1.73 m2) in combination with ribavirin, children with European Paediatric Hepatitis C Virus Network: Three broad
been found to predict a higher rate of spontaneous viral clear- genotype 1 achieved an SVR of 46%, and in a trial using pegy- modalities in the natural history of vertically acquired hepatitis
ance. lated IFNα-2b (1.5 µg/kg) + ribavirin an SVR of 48% was docu- C virus infection. Clin Infect Dis 2005; 41: 45–51.
mented in patients infected with genotype 1 and a remarkable Goodman ZD, Makhlouf HR, Liu L, Balistreri W, Gonzalez-
햵 — Histological changes are usually mild both in children
쏹 SVR of 100% in children and adolescents infected with genotype Peralta RP, Haber B, Jonas MM, et al: Pathology of chronic
with normal transaminases and in those with elevated transami- 2 or 3. hepatitis C in children: liver biopsy findings in the Peds-C Trial.
nases. Steatosis of minimal degree is present in approximately Hepatology 2008; 47: 836–843.
40% of the infected children. Fibrosis grades are generally low 햷 — The most common adverse effect of ribavirin therapy is
쏹 Iorio R, Giannattasio A, Sepe A, Terraciano LM, Vecchione R,
and fibrosis progression is relatively slow with an inconclusive hemolytic anemia. It is dose dependent and usually occurs dur- Vegnente A: Chronic hepatitis C in childhood: an 18-year expe-
correlation with the duration of disease. In a recent study of 121 ing the first 4 weeks of therapy. In animal studies, ribavirin has rience. Clin Infect Dis 2005; 41: 1431–1437.
treatment-naïve children aged 2–16 years (mean age 9.8 years), been shown to have teratogenic and embryotoxic effects, war- Karnsakul W, Alford MK, Schwarz KB: Managing pediatric hep-
bridging fibrosis was observed in only 5 of the children. Over- ranting caution and contraception advise when treating adoles- atitis C: current and emerging treatment options. Ther Clin
weight children were noted to have more fibrosis than nonover- cents. Risk Manag 2009; 5: 651–660.
weight children. Cirrhosis is rare and estimated to occur in 1.8– Mack CL, Gonzalez-Peralta RP, Gupta N, Leung D, Narkewicz
4.7% of children, mainly those who were infected perinatally, MR, Roberts EA, et al: NASPGHAN practice guidelines: diag-
have persistent viral replication and are infected with HCV geno- nosis and management of hepatitis C infection in infants, chil-
type 1a. Hepatocellular carcinoma can occur in the pediatric age dren, and adolescents. J Pediatr Gastroenterol Nutr 2012; 54:
group but is extremely rare, so that these patients have been 838–855.
the subject of case reports. Schwarz KB, Mohan P, Narkewicz MR, Molleston JP, Nash SR,
Hu S, Wang K, Gries JM: Safety, efficacy and pharmacokinet-
ics of peginterferon alpha 2a in children with chronic hepatitis
C. J Pediatr Gastroenterol Nutr 2006; 43: 499–505.
Wirth S, Pieper-Boustani H, Lang T, Ballauff A, Kullmer U,
Gerner P, Wintermeyer P, Jenke A: Peginterferon alpha-2b
plus ribavirin treatment in children and adolescents with
chronic hepatitis C. Hepatology 2005; 41: 1013–1018.
81
햲
Elevated aminotransferases
82 History and physical examination
Retest with synthetic function (albumin, INR) and CK to confirm elevation
Normal Abnormal 햳
Children US Tests Tests Test for Recheck Anorexia Thyroid Celiac Adrenal Muscle Hemolysis
at risk Ceruloplasmin Ferritin HCV, after nervosa disease disease insuffi- disease (usually
24-hour urine Percent iron HBC antigen, 6–8 weeks ciency isolated
copper saturation other of AST)
Slit-lamp test HFE mutation viruses abstinence
Yes No for Kayser-
Fleischer rings
Test for No further HCV RNA TSH, Total IgA, Cortisol, AST/ALT >3
HBV/HCV assessment or T3, T4 TTGA, aldo- Cpk ↑ LDH ↑
HBV DNA antiendo- sterone, aldolase
mysial glucose,
Treat Immuno- antibody, electro-
underlying globulins DGPA lytes
Positive Negative
risk factors ANA,
anti-SMA See
neonatal
jaundice
Test for algorithm,
HBV DNA or p. 74
HCV RNA
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햲 — LFT are a helpful screening tool and an effective modality
쏹 햳 — The differential diagnosis for prolonged elevated liver
쏹 Selected reading
to detect hepatic dysfunction. Aminotransferases are the most enzymes include the spectrum of NAFLD, usually related to obe-
frequently utilized and specific indicators of hepatocellular dam- sity, AIH, Wilson’s disease, hemochromatosis, viral hepatitis, D’Agata ID Balistreri WF: Evaluation of liver disease in the
age. These enzymes – AST (formerly named serum glutamate alcohol- or drug-related disorders, or may be related to an ex- pediatric patient. Pediatr Rev 1999; 20: 376–390.
oxaloacetic transaminase) and ALT (formerly named serum glu- trahepatic disorder. Elevated AST may be due to muscle dis- Pratt DS, Kaplan MM: Evaluation of abnormal liver-enzyme
tamic pyruvate transaminase) – catalyze the transfer of the ease, hemolysis or macro-AST. Abnormal liver enzymes can results in asymptomatic patients. N Engl J Med 2000; 342:
α-amino acids of aspartate and alanine, respectively, to the also be noted in anorexia nervosa, thyroid disorders, celiac 1266–1271.
α-keto group of ketoglutaric acid. ALT is primarily localized to disease and adrenal insufficiency. Thapa BR, Walia A: Liver function tests and their interpreta-
the liver, but AST is present in a wide variety of tissues such as tion. Indian J Pediatr 2007; 74: 663–671.
the heart, skeletal muscle, kidney, brain and liver. In every as-
sessment of a child with elevated aminotransferases, there is a
need to rule out a nonhepatic etiology. The presence of elevated
conjugated bilirubin and/or elevated ALKP and GGT requires
further and usually more urgent assessment. PT and albumin as
markers of liver function should be part of the investigation of a
child or infant with elevated liver enzymes.
83
Normal Increased
Other etiology found AMA+ and US Dilated bile ducts 햷 AMA– and US
normal or normal 햸
AMA– and
hepatic parenchyma
abnormal 햶
Degree of ALKP elevation
>50% <50%
elevated elevated
Test for bone Consider liver biopsy Liver biopsy MRCP/ERCP Liver biopsy Observation
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ALKPs are a family of zinc metalloenzymes with a serine at the 햳 — TH of infancy and early childhood is defined as a marked
쏹 Selected reading
active center; they release inorganic phosphate from various elevation of ALKP activity in the serum of children younger than
organic orthophosphates and are present in nearly all tissues. In 5 years in the absence of clinical or laboratory findings of liver D’agata ID Balistreri WF: Evaluation of liver disease in the pe-
liver, ALKP is found histochemically in the microvilli of bile can- or bone disease. TH is frequently an incidental finding detected diatric patient. Pediatr Rev 1999; 20: 376–390.
aliculi and on the sinusoidal surface of hepatocytes. ALKPs from during routine blood chemistry analysis or in patients with vari- Dori N, Levi L, Stam T, Sukhotnik I, Shaoul R: Transient hyper-
the liver, bone and kidney are thought to be from the same ous childhood illnesses. TH is considered a benign condition in phosphatasemia in children revisited. Pediatr Int 2010; 52: 866–
gene; however, those from the intestine and placenta are de- children, and the elevated serum ALKP levels usually return to 871.
rived from different genes. In the liver, two distinct forms of normal within 4–6 months. Pratt DS, Kaplan MM: Evaluation of abnormal liver-enzyme
ALKPs are also found, but their precise roles are unknown. In results in asymptomatic patients. N Engl J Med 2000; 342:
healthy individuals, most circulating ALKP originates from the 햴 — There might also be a physiologic increase during preg-
쏹 1266–1271.
liver or bone. In normal healthy children, the bone and liver nancy, postprandially and after fasting. Siddique A, Kowdley KV: Approach to a patient with elevated
fractions predominate. The serum level of ALKP changes with serum alkaline phosphatase. Clin Liver Dis 2012; 16: 199–229.
age; compared to adult levels, it is mildly elevated during the 햵 — In case of suspected cholestatic liver disease, a complete
쏹 Thapa BR, Walia A: Liver function tests and their interpreta-
first 3 months of life, increases at puberty by two- to three-fold investigation should be done (see neonatal jaundice algorithm, tion. Indian J Pediatr 2007; 74: 663–671.
and remains above the adult level for 1 or 2 years. This increase p. 74). US and an AMA test should also be performed although
is related to the bone growth spurt during puberty. PBC has rarely been reported in pediatric patients.
85
Abnormal Type 1 AILD and normal transaminase levels, negative autoantibody titers for >1 year
transaminase levels = on maintenance treatment and no relapses (not during or before puberty!) 햻
relapse 햺
Pulse steroids
No inflammation Inflammation
on liver biopsy on liver biopsy
Consider alternative treatment to replace azathioprine, Attempt to stop treatment Continue with treatment
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Evaluation cell infiltrate in the portal tracts, infiltrating the parenchyma (interface cases. Nonadherence, as a possible cause of treatment failure, should
All children and adolescents presenting with abnormal LFT after ex- hepatitis). The presence of biliary features on liver histology and/or be thoroughly investigated.
cluding viral hepatitis with appropriate investigations should be in- an abnormal cholangiography support the diagnosis of ASC, whereas
vestigated for AILD. the absence of both features leads to the diagnosis of AIH. An abnor- 햹 — Once the transaminase levels have normalized and the dose of
쏹
There are three liver disorders, in which liver damage is likely to arise mal cholangiogram, however, can be present also when the liver bi- prednisolone has successfully been decreased to a daily maintenance
from an autoimmune attack: AIH, ASC, which is included in the scleros- opsy does not show biliary features. dose of 2.5 or 5 mg, transaminase levels, IgG and autoantibody titers,
ing cholangitis algorithm (p. 88), and de novo AIH after liver transplant. all sensitive markers of disease activity, should be monitored at regu-
The management of the latter will not be discussed in this algorithm. 햵 — AILD is treated with immunosuppressive drugs. The first-line
쏹 lar intervals (ideally 3 monthly).
treatment consists of oral prednisolone, given once a day, at a dose
of 2 mg/kg/day (maximum dose of 60 mg/day). The treatment ideally 햺 — Abnormal transaminase levels during regular monitoring and
쏹
History
should be commenced in hospital for close monitoring of blood sug- on maintenance treatment suggest relapse of AILD and should be
AILD can present as ALF, acute hepatitis, chronic hepatitis or with
ar, blood pressure and neurological status to assess possible side managed with increased doses of oral prednisolone (up to 2 mg/kg/
complications of chronic liver disease. In AIH, there is a female pre-
effects. LFT and clotting profiles should be monitored on a daily ba- day) aiming at a progressive normalization of the transaminases.
ponderance; in ASC, 50% of the patients are male. Approximately 20%
sis. While on high-dose prednisolone, H2 blockers should be added Monitoring should be close to avoid steroid toxicity. Nonadherence
of the patients have associated autoimmune disease affecting other
for gastric protection. Fat- and water-soluble vitamin supplements are should be thoroughly investigated. In case of frequent relapses, alter-
organs and 40% a positive family history of autoimmune disorders.
indicated. If the diagnosis of ASC is suspected or confirmed, ursode- native treatments as discussed above should be considered if not yet
Physical examination oxycholic acid (15 mg/kg twice a day) should be added. implemented.
Evidence of acute hepatitis with jaundice, tiredness and poor appetite 햻 — In patients with type 1 AILD, in whom transaminase levels and
쏹
associated with encephalopathy in case of fulminant liver failure pre- 햶 — If a progressive normalization of the transaminases is not ob-
쏹
tained during the first 6–8 weeks of treatment or the dose of predniso- IgG have been normal with negative or less than 1:20 autoantibody
sentation. titer by immunofluorescence testing for more than 1 year, in the ab-
Evidence of chronic liver disease with splenomegaly, palmar erythe- lone required to maintain a steady fall of the transaminases is too
high, second-line azathioprine can be added as steroid-sparing agent. sence of relapses, discontinuation of treatment can be considered;
ma, spider naevi and cutaneous shunts. Rarely peripheral edema and however, this should never be attempted before or during puberty as
ascites. Azathioprine is not recommended as first-line treatment because of its
hepatotoxicity especially in severely jaundiced patients. The starting the risk of relapse is particularly elevated during this period. When
dose is 0.5 mg/kg/day, which can be increased gradually in the ab- considering stopping the treatment, a liver biopsy should be carried
Laboratory examination
sence of toxicity (e.g. bone marrow suppression) to 2 mg/kg/day. Aza- out to assess the degree of inflammation and compare with previous
Clotting profile, LFT including bilirubin (plus conjugated fraction), se-
thioprine metabolite (6-thioguanine and 6-mercaptopurine) measure- histology where possible. If despite normal transaminase levels in-
rum transaminases, GGT, albumin and full blood count.
ments, as used in IBD, have been suggested to be useful in identifying flammation is still present, treatment should not be discontinued be-
Immunoglobulins, autoantibodies (including ANA, SMA, liver kidney
drug toxicity and nonadherence as well as in achieving therapeutic cause of the high risk of relapse. If no inflammation is present, cessa-
microsomal antibody type 1, and, whenever possible, antiliver cyto-
levels of 6-thioguanine also in patients with AIH. tion of treatment can be attempted.
sol type 1, antisoluble liver antigen) and complement.
햷 — Transaminase levels and clotting profiles should be monitored
쏹
햽 — When discontinuing treatment, second-line treatment (e.g.
쏹
햲 — AILD is an inflammatory liver disorder characterized serologi-
쏹 azathioprine, MMF) should be gradually decreased and eventually
cally by the presence of nonorgan and liver-specific autoantibodies weekly during the first 6–8 weeks of treatment aiming at obtaining at
least an 80% decrease of the initial transaminase levels, usually fol- stopped under close monitoring of the transaminase levels. Subse-
and increased levels of IgG in the absence of a known etiology. It is quently, the dose of prednisolone should be very slowly decreased
important that other causes of liver disease, where autoantibodies lowed by a complete normalization of the transaminase levels within
6–9 months. A rapid complete normalization of the transaminase lev- and stopped. Following cessation of treatment, transaminase levels
can be positive, such as Wilson’s disease, nonalcoholic steatohepati- should be monitored 3 monthly for 1 year, 6 monthly for 1 year and
tis and viral hepatitis caused by HBV or HCV, are excluded before a els at the cost of steroid toxicity has no prognostic advantages. The
steroid dose should be decreased in parallel to the decrease of the then yearly for a few years.
diagnosis of AILD is made. Depending on the autoantibodies present,
AIH is divided into type 1 AIH, characterized by ANA ± SMA, and type transaminase levels, hence the need for regular monitoring. The aim
2, positive for liver kidney microsomal antibody type 1 or antiliver is to decrease the dose of prednisolone as soon as possible to a main-
Selected reading
cytosol type 1. ASC is usually positive for ANA and/or SMA. Antisolu- tenance dose of 2.5–5 mg/day, depending on the age of the child. Dai-
ble liver antigen characterizes a particularly severe phenotype. ly treatment is important in AILD since there is a high incidence of re- Gossard AA, Lindor KD: Autoimmune hepatitis: a review. J Gastro-
lapse when alternate day treatment is attempted. If any other steroid- enterol 2012;47:498–503.
햳 — Baseline investigations in AILD include a clotting profile. If the
쏹 sparing agents are used, e.g. azathioprine or MMF, the dose of these Mieli-Vergani G, Vergani D: Autoimmune paediatric liver disease.
clotting is abnormal (INR >1.5), liver biopsy should be deferred until should not be altered while adjusting the dose of prednisolone. World J Gastroenterol 2008;14:3360–3367.
coagulation normalizes on immunosuppressive treatment. In rare Mieli-Vergani G, Vergani D: Autoimmune liver diseases in children –
cases, AILD can present as ALF with encephalopathy, for which liver 햸 — If transaminase levels fail to improve, azathioprine should be
쏹
what is different from adulthood? Best Pract Res Clin Gastroenterol
87 transplantation is the only therapeutic option. discontinued and alternative agents should be added to the predniso-
2011;25:783–795.
lone maintenance. We have obtained good results with MMF. We use
Mieli-Vergani G, Vergani D: Autoimmune hepatitis. Nat Rev Gastro-
햴 — If the clotting profile is normal and platelet count exceeds 70 ×
쏹 a starting dose of 10 mg/kg/day in two doses with a maximum daily
enterol Hepatol 2011;8:320–329.
109/l, a liver biopsy can be performed at presentation. In order to be dose of 40 mg/kg/day (maximum 1 g b.d.). The main side effects are
Roberts EA: Autoimmune hepatitis from the paediatric perspective.
able to distinguish between AIH and ASC, a cholangiography is indi- bone marrow suppression and GI discomfort. Levels can be mea-
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Liver G. Mieli-Vergani · M. Samyn Autoimmune liver disease
Liver G. Mieli-Vergani · M. Samyn Sclerosing cholangitis
Sclerosing cholangitis
88
Infancy Childhood to adolescence
Obstructive jaundice ± pale stools Obstructive jaundice ± pruritus
No evidence or history of gallstones
Investigations Investigations
Blood tests and urine Blood tests including immunoglobulins and autoantibodies
US scan Imaging
Liver US scan
Gallbladder MRCP
Splenic abnormalities ERCP (by experienced operator)
BA
NSC Monitor
AFP and Ca199
Proceed to Kasai Rx ursodeoxycholic acid
US scan
portoenterostomy Supportive management
If indicated, follow-up MRCP/ERCP
(not in BA)
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— Every infant presenting with obstructive jaundice requires fur-
• Liver biopsy • Langerhans cell histiocytosis: in this rare systemic immunological/
ther investigations as to the etiology of the obstructive jaundice. It is A liver biopsy is indicated but should be considered carefully be- oncological condition, the involvement of the liver and biliary sys-
important for health professionals to assess the stool and urine color cause of the possibility of biliary complications if bile ducts are di- tem leads to a cholangiopathy. Liver transplantation is indicated in
personally. lated. It is to be avoided in sickle cell disease where mortality is end-stage liver disease but should only be considered if the sys-
high if liver biopsy is carried out during a sickle crisis. temic condition is in remission because of the risk of recurrence.
— In older children presenting with obstructive jaundice and/or
pruritus and in the absence of gallstones, further investigations to — Liver biopsy
— If BA is suspected, further management by a pediatric hepato-
look for an underlying cholangiopathy are indicated. A liver biopsy should only be carried out by an experienced person biliary surgeon with laparotomy and intraoperative cholangiography
providing the patient’s clotting profile is within the normal limits and to assess the extra- and intrahepatic bile duct patency is required. If
— Investigations include:
the patient is clinically stable. Histopathological changes of distal bile the biliary system is not patent at the time of laparotomy, confirming
• Blood tests
duct obstruction (expansion of portal tracts with bile duct prolifera- the diagnosis of BA, the surgeon will proceed to a Kasai portoenter-
Total and conjugated serum bilirubin
tion and presence of intracanalicular bile plugs) suggest BA. Other ostomy. The outcome is significantly better if the procedure takes
AST, ALT, GGT (low GGT can be suggestive of PFIC)
changes such as bile duct paucity (as seen in Alagille syndrome) or place prior to the age of 100 days.
Synthetic function, clotting profile
intrahepatic cholestasis with giant cell transformation (as seen in
Full blood count including blood film and hemolytic screen if
BSEP deficiency) can be described. In a neonate with α1-antitrypsin — In NSC, a condition with an autosomal-recessive mode of in-
indicated heritance in most cases, the extra- and intrahepatic biliary systems
deficiency presenting with a cholestatic jaundice, the histopathologi-
α1-Antitrypsin phenotype are thin and irregular on direct biliary imaging. Prior to confirming
cal findings on a liver biopsy can mimic BA.
CF genotype or immunoreactive trypsin the diagnosis, other conditions such as Alagille syndrome (bile duct
Cortisol and thyroid function test — If the findings on liver histology are inconclusive and/or if the
hypoplasia) need to be excluded. The management of NSC is sup-
Cholesterol and TG stool color is intermittently pale, further imaging of the biliary tract portive with fat and water-soluble vitamin supplements, MCT-based
• Urine can be organized such as ERCP, which should be performed by an feed and ursodeoxycholic acid 10 mg/kg maximum 3 times/day.
Microscopy and culture experienced operator. Failure to cannulate the ampulla or visualize
Reducing substances to exclude galactosemia the biliary system and/or absence of the bile in the duodenum war- — Monitoring for all patients with a cholangiopathy includes
Organic and amino acids rant further surgical assessment with laparotomy and intraoperative regular follow-up (6 monthly if evidence of chronic liver disease) in a
Bile acid profile cholangiography. center with pediatric hepatology experience with blood tests includ-
• US scan ing AFP (tumor marker for hepatocellular carcinoma) and CA-199-9
When done by an experienced ultrasonographer, useful informa- — The presence of high immunoglobulin G levels, positive auto-
(tumor marker for cholangiocarcinoma) as well as imaging with US
tion can be obtained with the assessment of: antibodies (in particular ANA and anti-SMA), interface hepatitis and/ and, if indicated, MRCP/ERCP.
– Liver parenchyma (homogeneous, heterogeneous, or cholangiopathy on histological examination, and/or extra- and/or
intrahepatic cholangiopathy on MRCP/ERCP is diagnostic of ASC, — If the liver disease decompensates, liver transplantation
suggestion of fatty infiltration)
which needs to be treated accordingly (cf. autoimmune liver disease should be considered; however, cholangiocarcinoma is a contraindi-
– Biliary system: bile duct dilatation or presence of cystic
algorithm, p. 86). cation for liver transplantation because of the high risk of recurrence.
structure, biliary sludge in gallbladder or biliary system
Recurrence of disease after transplant is frequent in ASC, described
– Presence of gallbladder and description of shape and
— In the presence of a cholangiopathy on histology and/or
in PSC, and rare in other forms of SC such as BA and NSC.
wall, gallstones
MRCP/ERCP, but in the absence of autoimmune features and other
– Splenomegaly or splenic malformations such as
conditions associated with SC, the diagnosis of cryptogenic SC (pri-
asplenia and polysplenia which are associated with BA
mary SC) can be made, and further management includes the use of Selected reading
– Triangular cord sign (fibrotic structure at the liver hilum)
ursodeoxycholic acid (maximum dose 20 mg/kg/day).
described in BA Mieli-Vergani G, Vergani D: Autoimmune liver diseases in chil-
• Nuclear medicine scan
— In ASC and cryptogenic SC, further investigations to look for
dren – what is different from adulthood? Best Pract Res Clin Gas-
A DISIDA scan will assess liver function and excretion, very sensi- the presence of IBD are indicated as both conditions are associated troenterol 2011; 25: 783–795.
tive but not specific for BA with IBD and the bowel involvement can be quiescent at the time of Mieli-Vergani G, Vergani D: Sclerosing cholangitis in the paediat-
• MRCP the hepatic presentation. ric patient. Best Pract Res Clin Gastroenterol 2001; 15: 681–690.
Can be helpful in the presence of bile duct dilatation to deter- Mieli-Vergani G, Vergani D: Unique features of primary sclerosing
mine the anatomy. Difficult to interpret in infants where no — Some conditions have been associated with a cholangiopa-
thy, which has been labeled secondary SC. cholangitis in children. Curr Opin Gastroenterol 2010; 26: 265–268.
bile duct dilatation is present. Ponsioen CY: Recent insights in primary sclerosing cholangitis. J
• Immunodeficiencies, in particular hyper-IgM syndrome, where SC
— Investigations include:
is related to colonization of the biliary system by Cryptosporidium. Dig Dis 2012; 13: 337–341.
• Blood tests with full chronic liver disease workup including baseline The presence of Cryptosporidium in the stools and/or liver biopsy Shneider BL: Diagnostic and therapeutic challenges in pediatric
89 liver profile, immunoglobulins and liver-specific autoantibodies should be actively sought to start the appropriate treatment (paro- primary sclerosing cholangitis. Liver Transpl 2012; 18: 277–281.
• Imaging momycin). Filtered water should be used as Cryptosporidium pro- Trivedi PJ, Hirschfield GM: Review article: overlap syndromes
– US scan phylaxis. If bone marrow transplantation is considered, liver dis- and autoimmune liver disease. Aliment Pharmacol Ther 2012; 36:
– MR cholangiography: currently, first-line investigation for more ease needs to be assessed, and sequential liver and bone marrow 517–533.
detailed imaging of the biliary system. If inconclusive further di- transplantation should be considered.
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Liver G. Mieli-Vergani · M. Samyn Sclerosing cholangitis
Liver G. Mieli-Vergani · M. Samyn Acute liver failure
Basic investigations 햳
LFT, PT or INR, full blood count, blood sugar, renal function tests, blood gasses
Hepatic encephalopathy grade II with agitation or grade III/IV Hepatic encephalopathy grades I–II
Liver transplantation 햷
Kainan University
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햲 — Definition and presentation
쏹 • Drugs and toxins can cause liver failure in children. Risk fac- 햷 — Liver transplantation
쏹
• ALF in children is a rare multisystemic disorder, in which tors are age (very young or adolescents), abnormal renal • The most common type of liver transplantation in children is
severe impairment of liver function, with or without enceph- function, concomitant use of other hepatotoxic agents, drug orthotopic liver transplantation with a split liver. Living-relat-
alopathy, occurs in association with hepatocellular necrosis interactions and preexisting liver disease. Drug-induced ed donation can be considered in ALF and requires rapid as-
in a patient with no recognized underlying chronic liver dis- hepatotoxicity can be a dose-dependent response, an idio- sessment of the donor. The 1-year survival in children after
ease. syncratic reaction or a synergistic reaction. liver transplantation for ALF is currently 75%.
• Liver function is severely impaired when: (a) PT >15 s or INR • Metabolic conditions include galactosemia, tyrosinemia, he- • Auxiliary liver transplantation is used in ALF because of the
>1.5 is not corrected by vitamin K in the presence of HE, and reditary fructose intolerance and neonatal hemochromatosis regenerative potential of the native liver, if given sufficient
(b) PT >20 s or INR >2.0 in the absence of HE. in infancy and Wilson’s disease in childhood. Fatty acid oxi- time to recover. The auxiliary graft provides liver function,
• The most common symptoms are fatigue, nausea and ab- dation defects and inborn errors of bile acid metabolism while the native liver regenerates. Auxiliary liver transplan-
dominal pain followed by jaundice. need to be considered. Mitochondrial disorders have been tation should not be considered in patients who are diag-
• The clinical examination is often nonspecific. Jaundice is included in the etiology of ALF in children over recent years. nosed with an underlying chronic liver disease such as AILD
usually present, whereas hepatosplenomegaly is uncom- • Miscellaneous causes of ALF in children include AILD, vas- or Wilson’s disease.
mon. Symptoms such as skin rash, joint pain, concentration cular causes (e.g. Budd-Chiari syndrome, veno-occlusive • In our center, 60% of children who have undergone auxiliary
problems, etc. may suggest specific etiologies, e.g. autoim- disease and cardiomyopathies) and malignancies (e.g. he- liver transplantation for ALF have regenerated their own liv-
mune or metabolic etiologies. mophagocytic lymphohistiocytosis, leukemia and lympho- er and have been taken off immunosuppression.
• Taking a detailed medical and family history is essential. Re- ma). • Hepatocyte transplantation to provide a functioning hepatic
cent travels or contact with jaundiced people suggest viral • Indeterminate or non-A-E hepatitis is diagnosed when all mass while the native liver regenerates is still experimental
hepatitis, whereas drug exposure suggests toxic hepatitis. other causes of ALF are eliminated by appropriate labora- but could potentially be used as a bridge to transplantation.
tory investigations and clinical examination. • The prognosis of ALF varies greatly with the underlying
햳 — LFT are abnormal with raised transaminase (ALT, AST)
쏹 etiology, the clotting profile being the best predictor of sur-
and bilirubin levels. AST and ALT levels can be in their thou- 햶 — If the INR is >4, the changes of survival without liver
쏹 vival.
sands. High transaminases with minimally elevated bilirubin transplantation are small, unless in stable paracetamol over-
levels suggest a metabolic disorder (e.g. fatty acid oxidation de- dose, mitochondrial disorders and fatty oxidation defects. Selected reading
fect or mitochondrial cytopathy) or acetaminophen toxicity. • Contraindications to transplantation include: permanently
High conjugated bilirubin levels with nearly normal transami- fixed and dilated pupils; uncontrolled active sepsis; severe Devictor D, Tissieres P, Afanetti M, Debray D: Acute liver fail-
nase levels in the neonate suggest neonatal hemochromatosis. respiratory failure (ARDS); diagnosis of mitochondrial disor- ure in children. Clin Res Hepatol Gastroenterol 2011; 35: 430–
Clotting tests (PT or INR) are the most important to determine der with neurological involvement. 437.
the severity of liver damage. In the presence of abnormal PT or • Relative contraindications include: accelerating inotropic re- Bansal S, Dhawan A: Acute liver failure; in Kleinman RE, Gou-
INR, evidence of DIC must be assessed. quirements; infection under treatment; cerebral perfusion let OJ, Mieli-Vergani G, Sanderson IR, Sherman P, Shneider
pressure <40 mm Hg for >2 h; history of progressive or se- BL (eds): Walker’s Pediatric Gastrointestinal Disease, ed 5.
햴 — Investigations to determine the cause of ALF include:
쏹 vere neurological problems, in which the ultimate neurologi- Hamilton, Decker, 2008, pp 1117–1129.
• Biochemistry, full blood count and clotting profile, immunol- cal outcome might not be acceptable; convulsions. Shanmugam NP, Bansal S, Greenough A, Verma A, Dhawan
ogy, virology and bacteriology A: Neonatal liver failure: aetiologies and management – state
• Urine including penicillamine challenge for urinary copper of the art. Eur J Pediatr 2011; 170: 573–581.
estimation in older children, when possible
• Liver US scan
• Bone marrow aspirate, muscle and skin biopsy if indicated
• Liver biopsy is rarely helpful and contraindicated because of
coagulopathy
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Liver G. Mieli-Vergani · M. Samyn Acute liver failure
Liver E. Fitzpatrick · A. Dhawan Hepatomegaly
Hepatomegaly
92
Splenomegaly No splenomegaly
Chronic liver Hematological Malignancies 햸 Infections 햹 Metabolic Storage Over- or Glycogen Tumors 햸 Hematological Heart
disease with disorders 햷 Leukemia, EBV, CMV disorders disorders undernutrition hepatopathy Hepatoblastoma, disorders 햷 failure 헀
secondary portal Thalassemia lymphoma, Mucopoly- GSD (fatty liver) 햾 (Mauriac’s hepatocellular Sickle cell
hypertension hemophago- saccharidoses 햺 (except syndrome) 햿 carcinoma, disease
į1-Antitrypsin cytic lympho- Lysosomal type IV) 햽 hemangioendo-
deficiency 햳 histiocytosis, disorders 햺 thelioma, other
Congenital hepatic Langerhans cell Peroxisomal malignant tumors
fibrosis 햴 histiocytosis disorders 햻
CFALD 햵
Wilson’s disease
AILD
Chronic viral
hepatitis
Budd-Chiari syndrome 햶
GSD type IV
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Liver E. Fitzpatrick · A. Dhawan Hepatomegaly
Liver E. Broide · S. Reif Gallstones
Gallstones
94
Obtain history
Yes No
Infancy Childhood/
adulthood Biliary Fever Elevated Pancreatitis Continue clinical +
pain chills canalicular US follow-up
enzymes
95
Portal hypertension
96
Laboratory studies
Imaging/endoscopy
bleeding episode) are β-blocker therapy in combination with sclero- Shneider BL, Bosch J, de Franchis R, Emre SH, Groszmann RJ, Ling
size and the presence of red wale sign and cherry red spot are associ- SC, et al: Portal hypertension in children: expert pediatric opinion on
ated with an increased risk of hemorrhage. therapy or band ligation, portosystemic shunting (TIPS or surgical
shunt) and liver transplantation. the report of the Baveno V Consensus Workshop on Methodology of
97 Diagnosis and Therapy in Portal Hypertension. Pediatr Transplant
Therapy Sclerotherapy: several randomized studies have demonstrated that
The therapy of PH is directed at the management of variceal hemor- sclerotherapy initiated after the first bleeding episode reduces long- 2012;16:426–437.
rhage and divided into prophylaxis (primary) of the first episode of term morbidity and mortality. The main complications of sclerotherapy Superina R, Shneider B, Emre S, Sarin S, de Ville de Goyet J: Surgical
bleeding, emergency therapy and prophylaxis (secondary) of subse- are esophageal ulceration and stricture formation. guidelines for the management of extra-hepatic portal vein obstruc-
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Liver R. Arnon · A. Dhawan Portal hypertension
Liver A. Ben Tov · S. Reif Ascites
햲
Ascites
98
Abdominal paracentesis 햳
Multiple Single
organisms and organism
surgical source
of infection
R/O nephrotic
syndrome
Treat Treat Treat Treat i.v. antibiotics i.v. antibiotics Anti- Empirical Sodium Treat
underlying underlying underlying underlying Consider myco- i.v. antibiotics restriction 헂 underlying
causes causes causes causes surgery bacterials Diuretics causes
Kainan University
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햲 — Ascites is of Greek derivation (‘askos’) and refers to sack-
쏹 햷 — The presence of a high neutrophil count warrants the use
쏹 헀 — The most recent theory of ascitic fluid formation in cirrho-
쏹
like appearance. The word describes pathologic fluid accumula- of empirical antibiotics (usually third-generation cephalospo- sis is the peripheral arterial vasodilatation hypothesis. Portal
tion within the peritoneal cavity. The presentation of ascites in rins) even in cases with negative cultures. pressure increases above a critical threshold, and circulating
children is different from that in adults. The earliest symptom nitric oxide levels increase. Nitric oxide leads to vasodilatation.
might be modest weight gain. The first sign is dullness on per- 햸 — Chylous ascites can result from an injury or obstruction
쏹 As the state of vasodilatation worsens, plasma levels of vaso-
cussion in the flanks with shifting dullness. Ultrasonographic of the thoracic duct in its abdominal portion. The diagnosis is constrictor, sodium-retentive hormones increase, renal function
scans can detect as little as 100 ml of fluid in the abdomen. The made by the demonstration of milky ascitic fluid with a high deteriorates and decompensation occurs.
evaluation of a patient with ascites requires that the cause of protein and TG content as well as elevated lymphocyte count.
the ascites be established. In most cases, ascites appears as Treatment is based upon diet that contains mainly MCT and 헁 — The differential diagnosis includes right-sided heart fail-
쏹
part of a well-recognized illness such as cirrhosis, congestive high protein in order to decrease lymph flow and facilitate heal- ure, constrictive pericarditis and obstruction of the inferior vena
heart failure, or disseminated carcinomatosis. In these situa- ing of the thoracic duct. PN might be mandated. Other treat- cava as in vena cava web.
tions, the pediatrician should determine if the development of ments include octreotide and investigational laparotomy.
ascites is indeed a consequence of the basic underlying disease 헂 — Treating children with ascites has a similar approach to
쏹
and not due to the presence of a separate disease process. 햹 — The lack of difference between serum and ascites albu-
쏹 treating adults, though the aim of the treatment is not only to
min combined with a low neutrophil count suggests the pres- reduce the ascitic fluid but to encourage growth as well. Espe-
햳 — Diagnostic paracentesis (50–100 ml) should be part of the
쏹 ence of ascites due to low oncotic pressure and albumin loss in cially when considering the possibility of liver transplantation in
routine evaluation of patients newly diagnosed with ascites. The the urine. Among the differential diagnoses in children, the the future. As treatment is started, baseline weight, electrolytes,
fluid should be examined for its gross appearance, protein con- most likely diagnosis is nephritic syndrome, which should ini- albumin, total protein, urea, creatinine and white blood cell
tent, albumin level, cell count, differential cell count, Gram and tially be treated with steroids. count should be obtained. The goal of diuretic treatment is to
acid-fast stains, bacterial culture, amylase, glucose, LDH, TG achieve a negative fluid balance of 10 ml/kg/day. Cirrhotic asci-
and cytology. Paracentesis may not be indicated in the initial 햺 — Pancreatic ascites occurs mainly in patients with severe
쏹 tes refractory to medical therapy requires the consideration of
diagnostic evaluation of ascites in a child with known liver dis- acute pancreatitis, chronic pancreatitis or pancreatic trauma. A using second-line (surgical) treatment such as TIPS or perito-
ease who presents without clinical deterioration in his chronic high amylase level in the ascitic fluid is indicative of pancreatic neovenous shunt as a bridge for transplantation. In fact, the
illness. ascites. evaluation for liver transplantation becomes urgent once ascites
has become diuretic resistant.
햴 — The SAAG should be calculated to determine if the fluid
쏹 햻 — Cytology has high sensitivity for the detection of perito-
쏹
has the features of a transudate or an exudate. The gradient cor- neal carcinomatosis.
relates directly with the portal pressure. Most of the time, a gra- Selected reading
dient >1.1 g/dl indicates PH. The SAAG categorizes ascites bet- 햽 — The importance of distinguishing this variant from spon-
쏹
ter than either the total protein concentration or other param- taneous bacterial peritonitis is that secondary peritonitis might Giefer MJ, Murray KF, Colletti RB: Pathophysiology, diagnosis,
eters. require emergency surgical intervention. and management of pediatric ascites. J Pediatr Gastroenterol
Nutr 2011; 52: 503–513.
햵 — An ascitic fluid neutrophil count ≥250/mm3 raises the
쏹 햾 — This is the most common bacterial infection of the ascitic
쏹 Hou W, Sanyal AJ: Ascites: diagnosis and management. Med
suspicion for infection. In fact, paracentesis is mandatory in the fluid. The infection is monomicrobial with a low bacterial con- Clin North Am 2009; 93: 801–817.
presence of unexplained fever and other signs of infection in centration. The current theory about the evolution of the spon- Runyon BA: Ascites and spontaneous bacterial peritonitis; in
any patient with known ascites as well as in any case of cirrho- taneous form of ascitic fluid infection consists of translocation Feldman M, Freidman LS, Brandt LJ (eds): Sleisenger &
sis decompensation. of microbes from the gut to the mesenteric lymph nodes, spon- Fordtran’s Gastrointestinal and Liver Disease, ed 8. Philadel-
taneous bacteremia and subsequent colonization of the ascitic phia, Saunders, 2006, pp 1935–1960.
햶 — The method of choice to obtain cultures consists of
쏹 fluid. Suzanne V, McDiarmid MB: End-stage liver disease; in Klein-
using blood culture battles instead of three agar plates. This man RE, Goult OJ, Shneider BL (eds): Walker’s Pediatric Gas-
method has high yield in detecting the offending pathogen. 햿 — In tuberculous peritonitis, there is a lymphocytic predom-
쏹 trointestinal Disease, ed 5. Shelton, People’s Medical Publish-
Bedside inoculation is superior to delayed laboratory inocula- inance of the ascitic fluid. This disease is more common in chil- ing House, 2008, pp 1131–1148.
tion. dren who suffer from concomitant HIV infection. Of note, 50% of
patients with tuberculous peritonitis have underlying cirrhosis.
99
Acute pancreatitis
100
Symptoms/signs/laboratory results 햲
Severity assessment 햳
Mild Severe
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In adults, the majority of cases are associated with gallstones, 햳 — The pediatric scoring system is a prognostic system for
쏹 Selected reading
alcohol abuse, hypercalcemia, hypertriglyceridemia, drugs and predicting the severity of an attack of acute pancreatitis in pedi-
blunt trauma. atric patients. One point is assigned for each category. Children Bai HX, Lowe ME, Husain SZ: What have we learned about
In children, the association with severe systemic illness such as who have a score >3 should be admitted to an intensive care acute pancreatitis in children? J Pediatr Gastroenterol Nutr
HUS is common, as are infectious (mainly viral) causes, struc- unit. Categories include the following: 2011; 52: 262–270.
tural disorders, e.g. pancreas divisum, and metabolic disorders, On admission: age <7 years, weight <23 kg, WBC count at onset Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH: Acute
e.g. GSD. Drugs causing pancreatitis in children include valproic >18,500/µl and LDH >2,000 IU/l. pancreatitis: value of CT in establishing prognosis. Radiology
acid and L-asparaginase. Genetic causes involve mutations of After 48 h: Ca <8.3 mg/dl, albumin <2.6 g/dl and a rise in urea 1990; 174: 331–336.
cationic trypsinogen (hereditary pancreatitis), serine protease >5 mg/dl in the first 48 h. DeBanto JR, Goday PS, Pedroso MR, Iftikhar R, Fazel A,
inhibitor Kazal type 1 (Spink 1) and the cftr gene. Nayyar S, Conwell DL, Demeo MT, Burton FR, Whitcomb DC,
햴 — US should be performed early, and the findings may in-
쏹 Ulrich CD 2nd, Gates LK Jr, Midwest Multicenter Pancreatic
햲 — One of the symptoms of acute pancreatitis is a sudden
쏹 clude pancreatic enlargement, altered echogenicity, dilated pan- Study Group: Acute pancreatitis in children. Am J Gastroen-
onset of epigastric pain radiating to the back. The pain is severe, creatic ducts, CBD or intrahepatic ducts, gallstones and sludge, terol 2002; 97: 1726–1731.
worsened by food and often accompanied by vomiting. In addi- pancreatic calcifications, cysts and fluid collections. CT scans Marik PE, Zaloga GP: Meta-analysis of parenteral nutrition
tion, the abdomen may be tender with localized guarding and should only be performed if there is deterioration. versus enteral nutrition in patients with acute pancreatitis.
rebound. There may be fever, tachycardia and occasionally hy- BMJ 2004; 328: 1407.
potension. Laboratory results include a rise in serum amylase 햵 — Local complications include fluid collections, pancreatic
쏹 Powell JJ, Miles R, Siriwardena AK: Antibiotic prophylaxis in
and lipase in excess of 3× normal. necrosis, abscesses, bleeding and pseudocyst formation. the initial management of severe acute pancreatitis. Br J Surg
1998; 85: 582–587.
Steer ML: Pathogenesis of acute pancreatitis. Digestion 1997;
58: 46–49.
101
햲
Chronic pancreatitis
102
Laboratory studies
Calcium
TG
Renal function
Sweat chloride concentration
IgG4 햳
Imaging 햴
US
EUS/MRCP
Normal Abnormal
Genetic testing 햵
PRSS1
SPINK1
CFTR
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햲 — Recurrent acute pancreatitis occurs in up to 10% of chil-
쏹 햵 — Genes associated with pancreatitis are consistent with
쏹 Selected reading
dren after an initial episode. The diagnosis of chronic pancreati- hypotheses underlying the pathophysiology of pancreatitis.
tis is based on a combination of clinical features (abdominal Genes such as cationic trypsinogen (PRSS1), anionic trypsino- Darge K, Anupindi S: Pancreatitis and the role of US, MRCP
pain consistent with pancreatic origin, evidence of exocrine gen (PRSS2), pancreatic secretory trypsin inhibitor (SPINK1), and ERCP. Pediatr Radiol 2009; 39(suppl 2):S153–S157.
pancreatic insufficiency and/or evidence of endocrine pancreatic and chymotrypsinogen C (CTRC) have been demonstrated to be Fusaroli P, Kypraios D, Caletti G, Eloubeidi MA: Pancreatico-
insufficiency) with suggestive imaging studies. In adult patients, involved in the regulation of trypsinogen autoactivation. The biliary endoscopic ultrasound: a systematic review of the lev-
pancreatic biopsy is considered the gold standard for diagnosis; CFTR gene, responsible for CF, encodes for a cAMP-dependent els of evidence, performance and outcomes. World J Gastro-
however, it is rarely, if ever, performed in children. chloride channel located in the apical membrane of the pancre- enterol 2012; 18: 4243–4256.
There are 4 main groups of causes (unlike for adults, in whom atic duct cells. Lowe ME: Pancreatitis in childhood. Curr Gastroenterol Rep
alcohol is the only cause): (1) structural, (2) familial or genetic, 2004; 6: 240–246.
(3) autoimmune, and (4) idiopathic. The differential diagnosis of chronic pancreatitis in childhood Morinville V, Husain SZ, Bai H, et al: Definitions of pancreatic
includes the following: pancreatitis and survey of present clinical practices. J Pediatr
햳 — Autoimmune pancreatitis is a recently described fibroin-
쏹 • CF Gastroenterol Nutr 2012; 55: 261–265.
flammatory disease that is characterized by raised serum levels • Hereditary pancreatitis Nydegger A, Couper RT, Oliver MR: Childhood pancreatitis. J
of IgG4 (in >70% of the cases) and an IgG4-positive lymphoplas- • Tropical calcific pancreatitis Gastroenterol Hepatol 2006; 21: 499–509.
macytic tissue infiltrate. A favorable and rapid clinical response • Inborn errors of metabolism (particularly branched-chain Solomon S, Whitcomb DC: Genetics of pancreatitis: an update
to oral steroid therapy is often seen. Biliary involvement is com- aminoacidemias) for clinicians and genetic counselors. Curr Gastroenterol Rep
mon, and the term IgG4-associated cholangitis has recently • Hyperlipidemias 2012; 14: 112–117.
been coined. • Partial lipodystrophy Webster GJ, Pereira SP, Chapman RW: Autoimmune pancre-
• Wilson’s disease atitis/IgG4-associated cholangitis and primary sclerosing chol-
햴 — Imaging plays a crucial role in the diagnosis of acute and
쏹 • Hemochromatosis angitis – overlapping or separate diseases? J Hepatol 2009; 51:
chronic pancreatitis in children, and US is the primary imaging • α1-Antitrypsin deficiency 398–402.
modality. The US study can be improved by incorporating high- • Fibrosing pancreatitis
resolution imaging, color Doppler, harmonic imaging and pan- • Alcohol
oramic view. CT is widely used for further evaluation. EUS and • Idiopathic diseases
MRI in combination with MRCP are emerging as the modalities
of choice. MRCP is noninvasive and radiation-free. It has a high The treatment of chronic pancreatitis in pediatric patients
potential to replace ERCP. consists of:
• Pain relief
• Pancreatic enzyme replacement therapy
• Insulin if indicated
103
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Congenital disorder of glycosylation 10 Down syndrome 50 Failure to pass flatus or feces 68
Congenital hepatic fibrosis 92 Drooling 20 Failure to pass meconium 42
Congenital infections 74 Drug-induced hepatitis 76 Failure to thrive 8, 26, 28, 30, 44, 50, 72
Congenital lactase deficiency 56 Drug-induced hepatotoxicity 90 Familial adenomatous polyposis 54
Congenital mesoblastic nephromas 66 Drug-induced malabsorption 56 Familial hamartomatous polyposis syndrome 54
Congenital myotonic dystrophy 38 Dry mucous membranes 4 Family history of migraine 32
Congenital sodium diarrhea 56 Dullness on percussion in the flanks 98 Fat malabsorption 10, 72
Congenital sucrase-isomaltase deficiency 56 Duodenal ulcers 12 Fatigue 90
Congestive heart failure 98 Duodenitis 16 Fatty acid oxidation defect 90
Constipation 2, 6, 18, 26, 28, 30, 36, 42, 44, 50, 68 Duplication 14 Fatty infiltration 88
Cool extremities 4 Dysautonomia 38 Fecal incontinence 40
Cough 26, 28, 30, 38, 68 Dysgerminoma 66 Feeding difficulties 38
Cowden’s disease 54 Dysmenorrhea 68 Feeding refusal 16, 26, 28, 30
Craniofacial syndromes 38 Dysphagia 2, 6, 16, 20, 26, 28, 30, 34, 38, 46 Fever 2, 4, 14, 16, 20, 26, 28, 30, 42, 46, 68, 70, 76, 92,
Cricopharyngeal achalasia 38 Dysphonia 20 94, 100
Crigler-Najjar syndrome 74 Dysplasia 64 Fibrosis 34, 78, 80, 92
Crohn’s colitis 60 Dyspnea 20, 68 Fistula 18
Crohn’s disease 18, 60, 62 Dystonic neck posturing 26 Fluid accumulation in the peritoneal cavity 98
Cushingoid features 66 Dysuria 68 Fluid collection 100
Cyanosis 38 Focal biliary cirrhosis 92
Cyclic vomiting 24 E Early satiety 6 Folate malabsorption 56
Cyclic vomiting syndrome 32 Eczema 6 Food allergy/intolerance 6, 10, 16, 22, 24
Cystic fibrosis 10, 16, 56, 74, 76 Edema of the lips 6 Food aversion 38
Cystic fibrosis-associated liver disease 92 Electrolyte malabsorption 72 Food hypersensitivity 6
Cystic mass 66, 88 Electrolyte transport defect 10 Forceful emesis 32
Cystic renal diseases 66 Elevated portal blood pressure 96 Foreign bodies 24
Embryonal carcinoma 66 Foul-smelling bulky stool 58
Dark urine 76 Encephalopathy 86 Functional abdominal pain 2, 68
D Deceleration of growth 46 Endocrine pancreatic insufficiency 102 Functional constipation 2
Decreased fertility 50 End-stage liver failure 72 Functional dysphagia 38
Decreased or absent bowel sounds 70 Enteral protein loss 48 Fungal infection 18
Dehydration 4, 24, 32, 72, 74 Enterocolitis 42
Delayed puberty 46, 50, 60 Eosinophilic disease 24 Gagging 38
Dental enamel hypoplasia 50 Eosinophilic enteropathy 56
G Galactosemia 24, 74, 90
Dental erosion 26, 28, 30 Eosinophilic esophagitis 6, 38 Gallstones 72, 94, 100
Dermatitis herpetiformis 50 Eosinophilic gastroenteritis 6 Gardner’s syndrome 54
Desaturation 20 Epigastric pain radiating to the back 100 Gastric ulcers 12
Developmental dyschezia 18 Epistaxis 12 Gastric varices 12
Diabetes mellitus type 1 50 Epithelial cell tumor 66 Gastritis 6, 12, 16, 24
Diarrhea 2, 4, 6, 14, 26, 28, 30, 40, 42, 44, 54, 60, 68, Esophageal dysphagia 38 Gastroenteritis 6, 24, 68
70, 72 Esophageal food impaction 6 Gastroesophageal reflux 22, 24
Diffuse rebound tenderness 70 Esophageal spasm 38 Gastroesophageal reflux disease 16, 22, 24
Dilated bowel 44 Esophageal stricture 26, 28, 30 Gastrointestinal bleeding 2, 12, 14, 92, 96
Dilated common bile duct 100 Esophageal varices 12, 96 Gastrointestinal duplications 66
Dilated pancreatic ducts 100 Esophagitis 12, 16, 26, 28, 30, 34 Gastrointestinal foreign bodies 20
Disaccharidase deficiency 10 Excoriation 18 Gastrointestinal hemorrhage 14
105 Disaccharide intolerance 10 Exocrine pancreatic insufficiency 56, 102 Gastrointestinal polyps 54
Dismotility 34 Extrahepatic disease 82 Gastroparesis 24
Disseminated carcinomatosis 98 Extrahepatic portal vein obstruction 12, 96 Gaucher’s disease 92
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Index
Index
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Micrognathia 38 Osteopenia 50 Poor appetite 86
Microvillus inclusion disease 10, 56 Ovarian mass 66 Poor feeding 42, 70
Migraine 24 Ovarian/testicular torsion 68 Poor growth 60
Milky fluid 98 Overnutrition 92 Poor weight gain 58
Mitochondrial cytopathy 90 Oxalate nephrolithiasis 72 Portal hypertension 14, 92, 96
Mittelschmerz 68 Portal tract expansion 74, 88
Motility disorder 10 P Pain 60 Portal vein thrombosis 96
Mucopolysaccharidoses 92 Pale stool 74, 88, 94 Positive energy balance 16
Multicystic kidney 66 Palmar erythema 86 Postgastroenteritis diarrhea 10
Multiorgan failure 100 Pancreas divisum 100 Precocious puberty 66
Murphy’s sign 94 Pancreatic ascites 98 Primary biliary cirrhosis 50, 76
Muscle disease 82 Pancreatic calcification 100 Primary/nonorganic failure to thrive 8
Muscle wasting 58 Pancreatic cysts 100 Primary hypomagnesemia 56
Myasthenia gravis 38 Pancreatic enlargement 100 Primary peritonitis 70
Myelodysplasia 40 Pancreatic necrosis 100 Progressive familial intrahepatic cholestasis 74
Myelomeningocele 40 Pancreatitis 24, 94, 100, 102 Protein-calorie malnutrition 56
MYH-associated polyposis 54 Para-adrenal mass 66 Protein-induced enterocolitis 6
Parietal (somatic) pain 68 Protein-losing enteropathy 48, 54
Nausea 6, 68, 70, 76, 90 Passage of a stone 68 Protein synthesis 48
N Neck pain 20 Paucity of body motion 70 Pruritus 88
Necrotizing enterocolitis 14, 22 Pearson’s syndrome 56 Pseudocyst formation 100
Negative energy balance 16 Pelvic floor dyssynergia 36 Pseudo-obstruction 24, 44
Neglect 16 Pelvic inflammatory disease 68 Psychological dysphagia 38
Neonatal hemochromatosis 90 Peptic disease 24 Pulmonary diseases 16
Neonatal lymphangiectasia 10 Peptic ulcer disease 12, 52 Pyloric stenosis 24
Neonatal sclerosing cholangitis 74, 88 Peptic ulcer 24
Nephrotic syndrome 70 Perforated appendicitis 68 Rapid transit 40
Neuroblastoma 66 Perforation of a viscus 68
R Rebound tenderness 68
Neurodegenerative disorders 38 Perianal abscess 18 Rectal prolapse 18, 54
Neurogenic problems 40 Perianal fissure 18 Rectal varices 96
Neurologic changes 24 Perianal pain 18 Recurrent episodes of nausea 32
Neurologic deficits 36 Perianal skin tags 60 Recurrent pneumonia 26, 28, 30
Neurological disorders 22 Peripheral edema 48, 86 Recurrent rectal bleeding 54
Niemann-Pick disease 92 Perirectal disease 2, 46 Recurrent regurgitation 26, 28, 30
Nocturnal diarrhea 2, 46 Peritonitis 20, 24 Recurrent vomiting 32
Nonalcoholic acute steatohepatitis 76 Periumbilical abdominal pain 2 Red flags 60
Nonalcoholic fatty liver disease 82 Peroxisomal disorders 92 Redness 18
Nonbilious vomiting 22 Peutz-Jeghers syndrome 54 Referred pain 68
Nonfunctional abdominal pain 2 Pharyngitis 68 Reflux disease 38
Nonretentive fecal soiling 40 Phenotypic diarrhea 56 Reflux esophagitis 38
Pigment gallstones 94 Renal ascites 98
O Obesity 16, 94 Pigmentation of abdominal wall 70 Renal colic 72
Obstruction 20, 24 Pigmented stool 74 Renal diseases 16
Obstructive jaundice 88 Pin worms 18 Residual/recurrent achalasia 34
Obstructive symptoms 42 Pleural and pericardial effusions 48 Respiratory infection 24
Occult gastrointestinal bleeding 14 Pneumonia 24 Respiratory symptoms 34
107 Odynophagia 38 Polycystic kidney 66 Restlessness 4, 70
Omphalitis 14 Polycystic liver disease 92 Rhabdomyosarcoma 66
Oro-motor problems 16 Polydipsia 68 Ribbon-like stools 42
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Index
Index
PJS Peutz-Jeghers syndrome RLQAP Right lower quadrant abdominal pain TNF Tumor necrosis factor
110 PLE Protein-losing enteropathy R/O Rule out TPMT Thiopurine S-methyltransferase
PMN Polymorphonuclear leukocytes SAAG Serum ascites-albumin gradient TPN Total parenteral nutrition
PN Parenteral nutrition SBS Short bowel syndrome TSH Thyroid-stimulating hormone
PPI Proton pump inhibitor SC Sclerosing cholangitis TTGA Transglutaminase IgA antibodies
PSC Pediatric sclerosing cholangitis SMA Smooth muscle antibodies UC Ulcerative colitis
PT Prothrombin time SOS Sinusoidal obstruction syndrome UGIS Upper gastrointestinal series
PTT Partial prothrombin time SPT Skin prick test ULN Upper limit of normal
PUD Peptic ulcer disease SSRI Selective serotonin reuptake inhibitor URI Upper respiratory infection
PVT Portal vein thrombosis SVR Sustained virologic response US Ultrasound
RAP Recurrent abdominal pain TG Triglycerides UTI Urinary tract infection
RBC Red blood cells TH Transient hyperphosphatasemia VCE Video capsule endoscopy
RIBA Recombinant immunoblot assay TIPS Transjugular intrahepatic porto- WBC White blood cell
systemic shunt