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Nelson
TEXTBOOK of
PEDIATRICS
Nelson
TEXTBOOK of
PEDIATRICS
EDITION 20

Robert M. Kliegman, MD
Professor and Chair Emeritus
Department of Pediatrics
Medical College of Wisconsin
Milwaukee, Wisconsin

Bonita F. Stanton, MD Nina F. Schor, MD, PhD

Vice-Dean of Research William H. Eilinger Professor and Chair
Professor of Pediatrics Department of Pediatrics
Wayne State University School of Medicine Professor
Detroit, Michigan Department of Neurology
Pediatrician-in-Chief
Joseph W. St Geme III, MD Golisano Children’s Hospital
Chair, Department of Pediatrics University of Rochester Medical Center
Professor of Pediatrics and Microbiology Rochester, New York
Perelman School of Medicine at the University of
Pennsylvania Editor Emeritus
Physician-in-Chief
Leonard and Madlyn Abramson Endowed Chair in Richard E. Behrman, MD
Pediatrics Nonprofit Healthcare and Educational
Children’s Hospital of Philadelphia Consultants to Medical Institutions
Philadelphia, Pennsylvania Santa Barbara, California
1600 John F. Kennedy Blvd.
Ste. 1800
Philadelphia, PA 19103-2899

NELSON TEXTBOOK OF PEDIATRICS, TWENTIETH EDITION ISBN: 978-1-4557-7566-8

International Edition ISBN: 978-0-323-35307-6

Copyright © 2016 by Elsevier, Inc.

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any
means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval
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This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).

Notices

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our understanding, changes in research methods, professional practices, or medical treatment may become
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Practitioners and researchers must always rely on their own experience and knowledge in evaluating
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With respect to any drug or pharmaceutical products identified, readers are advised to check the most
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Previous editions copyrighted 2011, 2007, 2004, 2000, 1996, 1992, 1987, 1983, 1979, 1975, 1969, 1964, 1959

International Standard Book Number: 978-1-4557-7566-8

Content Strategy Director: Mary Gatsch

Executive Content Strategist: Kate Dimock
Content Development Specialist: Jennifer Shreiner
Publishing Services Manager: Patricia Tannian
Senior Project Manager: John Casey

Printed in Canada

Last digit is the print number: 9 8 7 6 5 4 3 2 1

To the Child’s Physician and especially to those who through their expressed confidence
in past editions of this book have provided the stimulus for this revision.
Waldo E. Nelson, 9/e, 1969

This is as true in 2015 as it was in 1969.

R.M. Kliegman, 20/e, 2015
Contributors
Mark J. Abzug, MD Michael A. Alexander, MD Alia Y. Antoon, MD
Professor of Pediatrics Professor of Pediatrics and Rehabilitation Medicine Assistant Clinical Professor
Division of Pediatric Infectious Diseases Thomas Jefferson Medical College Department of Pediatrics
University of Colorado School of Medicine Philadelphia, Pennsylvania; Harvard Medical School
Children’s Hospital Colorado Emeritus Medical Staff Chief of Pediatrics
Aurora, Colorado Alfred I. duPont Hospital for Children Shriners Hospital for Children
Nonpolio Enteroviruses Wilmington, Delaware Boston, Massachusetts
Evaluation of the Child for Rehabilitative Services Burn Injuries
David R. Adams, MD, PhD Cold Injuries
National Human Genome Research Institute Omar Ali, MD
National Institutes of Health Assistant Professor Susan D. Apkon, MD
Bethesda, Maryland Department of Pediatrics Associate Professor
Genetic Approaches to Rare and Undiagnosed Medical College of Wisconsin Department of Rehabilitation Medicine
Diseases Division of Endocrinology University of Washington School of Medicine
Children’s Hospital of Wisconsin Director, Rehabilitation Medicine
Stewart L. Adelson, MD Milwaukee, Wisconsin Seattle Children’s Hospital
Assistant Clinical Professor Hyperpituitarism, Tall Stature, and Overgrowth Seattle, Washington
Department of Psychiatry Syndromes Ambulation Assistance
Columbia University College of Physicians and Hypofunction of the Testes
Surgeons Pseudoprecocity Resulting from Tumors of the Testes Stacy P. Ardoin, MD, MHS
Adjunct Clinical Assistant Professor Gynecomastia Associate Professor of Clinical Medicine
Weill Cornell Medical College of Cornell Adult and Pediatric Rheumatology
University Namasivayam Ambalavanan, MD The Ohio State University Wexner Medical Center
New York, New York Professor of Pediatrics Nationwide Children’s Hospital
Gay, Lesbian, and Bisexual Adolescents Division of Neonatology Columbus, Ohio
University of Alabama, Birmingham Systemic Lupus Erythematosus
John J. Aiken, MD, FACS, FAAP Birmingham, Alabama Vasculitis Syndromes
Professor of Surgery High-Risk Pregnancies
Division of Pediatric General and Thoracic Surgery The Fetus Monica I. Ardura, DO, MSCS
Medical College of Wisconsin Nervous System Disorders Assistant Professor of Pediatrics
The Children’s Hospital of Wisconsin Hypoxia-Ischemic Encephalopathy Section of Infectious Disease and Immunology
Milwaukee, Wisconsin Respiratory Tract Disorders The Ohio State University College of Medicine
Acute Appendicitis Jaundice and Hyperbilirubinemia in the Newborn Nationwide Children’s Hospital
Inguinal Hernias Kernicterus Columbus, Ohio
Epigastric Hernia Genitourinary System Hansen Disease (Mycobacterium leprae)
The Umbilicus
Begum Akay, MD Metabolic Disturbances Michelle M. Ariss, MD
Assistant Professor of Surgery The Endocrine System Assistant Professor
Division of Pediatric Surgery Department of Ophthalmology
Oakland University William Beaumont School of Karl E. Anderson, MD, FACP University of Missouri—Kansas City School of
Medicine Professor Medicine
Beaumont Health Departments of Preventive Medicine, Community Children’s Mercy Hospital
Royal Oak, Michigan Health, Internal Medicine, and Pharmacology Kansas City, Missouri
Surgical Conditions of the Anus and Rectum and Toxicology Growth and Development (Eye)
Director, Porphyria Laboratory and Center Examination of the Eye
Cezmi A. Akdis, MD University of Texas Medical Branch Abnormalities of Refraction and Accommodation
Professor of Immunology Galveston, Texas Disorders of Vision
Swiss Institute of Allergy and Asthma Research The Porphyrias Abnormalities of Pupil and Iris
Christine Kühne Center for Allergy Research and Disorders of Eye Movement and Alignment
Education Peter M. Anderson, MD, PhD Abnormalities of the Lids
Davos, Switzerland; Curtis Distinguished Professor Disorders of the Lacrimal System
Medical Faculty, University of Zurich Department of Pediatrics Disorders of the Conjunctiva
Zurich, Switzerland University of Texas MD Anderson Cancer Center Abnormalities of the Cornea
Allergy and the Immunologic Basis of Atopic Disease Houston, Texas Abnormalities of the Lens
Neoplasms of the Kidney Disorders of the Uveal Tract
Evaline A. Alessandrini, MD, MSCE Disorders of the Retina and Vitreous
Professor of Clinical Pediatrics Kelly K. Anthony, PhD, PLLC Abnormalities of the Optic Nerve
University of Cincinnati College of Medicine Assistant Professor Childhood Glaucoma
Division of Emergency Medicine Department of Psychiatry and Behavioral Sciences Orbital Abnormalities
Director, Quality Scholars Program in Health Care Duke University Medical Center Orbital Infections
Transformation Durham, North Carolina Injuries to the Eye
Cincinnati Children’s Hospital Medical Center Musculoskeletal Pain Syndromes
Cincinnati, Ohio Thaís Armangué, MD
Emergency Medical Services for Children: Outcomes Clinical Fellow and Predoctoral Researcher
and Risk Adjustment ICREA-IDIBAPS Neuroimmunology Program
Hospital Clinic
Barcelona, Spain
Autoimmune Encephalitis

vi

Carola A.S. Arndt, MD
Professor of Pediatrics
Department of Pediatrics and Adolescent Medicine
Division of Pediatric Hematology-Oncology
Mayo Clinic
Rochester, Minnesota
Soft Tissue Sarcomas
Neoplasms of Bone
Stephen S. Arnon, MD, MPH
Chief, Infant Botulism Treatment and Prevention
Program Branch
Division of Communicable Disease Control
Center for Infectious Diseases
California Department of Public Health
Richmond, California
Botulism (Clostridium botulinum)
Tetanus (Clostridium tetani)
Stephen C. Aronoff, MD, MBA
Professor and Waldo E. Nelson Chair
Department of Pediatrics
Temple University School of Medicine
Philadelphia, Pennsylvania
Cryptococcus neoformans
Histoplasmosis (Histoplasma capsulatum)
Paracoccidioides brasiliensis
Sporotrichosis (Sporothrix schenckii)
Zygomycosis (Mucormycosis)
Nonbacterial Food Poisoning
David M. Asher, MD
Supervisory Medical Officer
Chief, Laboratory of Bacterial and Transmissible
Spongiform Encephalopathy Agents
Center for Biologics Evaluation and Research
(CBER)
United States Food and Drug Administration
Silver Spring, Maryland
Transmissible Spongiform Encephalopathies
Ann Ashworth, PhD, Hon FRCPCH
Professor Emeritus
Department of Population Health
Nutrition Group
London School of Hygiene and Tropical Medicine
London, United Kingdom
Nutrition, Food Security, and Health
Barbara L. Asselin, MD
Professor of Pediatrics and Oncology
Department of Pediatrics
University of Rochester School of Medicine
Golisano Children’s Hospital
Rochester, New York
Epidemiology of Childhood and Adolescent Cancer
Joann L. Ater, MD
Associate Professor
Department of Pediatrics
University of Texas MD Anderson Cancer Center
Houston, Texas
Brain Tumors in Childhood
Neuroblastoma
Erika F. Augustine, MD
Assistant Professor of Neurology and Pediatrics
Division of Child Neurology
University of Rochester Medical Center
Rochester, New York
Dystonia
Marilyn C. Augustyn, MD
Professor of Pediatrics
Boston University School of Medicine
Boston Medical Center
Boston, Massachusetts
Impact of Violence on Children
Contributors vii
Ellis D. Avner, MD Christina Bales, MD
Professor Assistant Professor of Pediatrics
Departments of Pediatrics and Physiology University of Pennsylvania Perelman School of
Medical College of Wisconsin Medicine
Milwaukee, Wisconsin Attending Physician
Introduction to Glomerular Diseases Division of Gastroenterology, Hepatology, and
Clinical Evaluation of the Child with Hematuria Nutrition
Isolated Glomerular Diseases with Recurrent Gross The Children’s Hospital of Philadelphia
Hematuria Philadelphia, Pennsylvania
Glomerulonephritis Associated with Infections Intestinal Atresia, Stenosis, and Malrotation
Membranous Nephropathy
Membranoproliferative Glomerulonephritis William F. Balistreri, MD
Glomerulonephritis Associated with Systemic Lupus Medical Director Emeritus, Pediatric Liver Care
Erythematosus Center
Henoch-Schönlein Purpura Nephritis Division of Pediatric Gastroenterology, Hepatology,
Rapidly Progressive (Crescentic) Glomerulonephritis and Nutrition
Goodpasture Disease Cincinnati Children’s Hospital Medical Center
Hemolytic-Uremic Syndrome Cincinnati, Ohio
Upper Urinary Tract Causes of Hematuria Morphogenesis of the Liver and Biliary System
Hematologic Diseases Causing Hematuria Manifestations of Liver Disease
Anatomic Abnormalities Associated with Hematuria Cholestasis
Lower Urinary Tract Causes of Hematuria Metabolic Diseases of the Liver
Introduction to the Child with Proteinuria Viral Hepatitis
Transient Proteinuria Liver Disease Associated with Systemic Disorders
Orthostatic (Postural) Proteinuria Mitochondrial Hepatopathies
Fixed Proteinuria
Nephrotic Syndrome Robert S. Baltimore, MD
Tubular Function Professor of Pediatrics and Epidemiology
Renal Tubular Acidosis Clinical Professor of Nursing
Nephrogenic Diabetes Insipidus Associate Director of Hospital Epidemiology (for
Bartter and Gitelman Syndromes and Other Pediatrics)
Inherited Tubular Transport Abnormalities Yale-New Haven Hospital
Tubulointerstitial Nephritis New Haven, Connecticut
Toxic Nephropathy Listeria monocytogenes
Cortical Necrosis Pseudomonas, Burkholderia, and
Renal Failure Stenotrophomonas
Carlos A. Bacino, MD Manisha Balwani, MBBS, MS
Professor of Molecular and Human Genetics Assistant Professor
Baylor College of Medicine Departments of Medicine and Genetics and
Chief, Genetics Service Genomic Sciences
Director, Pediatric Genetics Clinic Icahn School of Medicine at Mount Sinai
Texas Children’s Hospital New York, New York
Houston, Texas The Porphyrias
Cytogenetics
Christine E. Barron, MD
Robert N. Baldassano, MD Associate Clinical Professor
Colman Family Chair in Pediatric Inflammatory Department of Pediatrics
Bowel Disease and Professor of Pediatrics Brown University Alpert Medical School
University of Pennsylvania Perelman School of Rhode Island Hospital
Medicine Providence, Rhode Island
Director, Center for Pediatric Inflammatory Bowel Adolescent Rape
Disease
The Children’s Hospital of Philadelphia Karyl S. Barron, MD
Philadelphia, Pennsylvania Deputy Director
Inflammatory Bowel Disease Division of Intramural Research
Eosinophilic Gastroenteritis National Institute of Allergy and Infectious
Diseases
Keith D. Baldwin, MD, MSPT, MPH National Institutes of Health
Assistant Professor Bethesda, Maryland
Department of Orthopaedic Surgery Amyloidosis
University of Pennsylvania Perelman School of
Medicine Dorsey M. Bass, MD
Neuromuscular Orthopaedics and Orthopaedic Associate Professor of Pediatrics
Trauma Division of Pediatric Gastroenterology
Children’s Hospital of Philadelphia Stanford University School of Medicine
Philadelphia, Pennsylvania Palo Alto, California
Growth and Development Rotaviruses, Caliciviruses, and Astroviruses
Evaluation of the Child
Torsional and Angular Deformities
Common Fractures
viii Contributors

Mark L. Batshaw, MD Susanne M. Benseler, MD, PhD Joshua A. Blatter, MD, MPH
Professor and Chairman Associate Professor, Faculty of Medicine Instructor in Pediatrics
Department of Pediatrics University of Calgary Division of Pediatric Allergy, Immunology, and
Associate Dean, Academic Affairs Pediatric Rheumatologist, Section Chief Pulmonary Medicine
George Washington University Rheumatology Associate Director, Pediatric Lung Transplantation
School of Medicine and Health Sciences Alberta Children’s Hospital Center
Executive Vice-President Calgary, Alberta, Canada Washington University School of Medicine in
Chief Academic Officer and Physician-in-Chief Central Nervous System Vasculitis St. Louis
Children’s National Medical Center St. Louis, Missouri
Washington, DC Daniel Bernstein, MD Congenital Disorders of the Lung
Intellectual Disability Alfred Woodley Salter and Mabel Smith Salter
Endowed Professor in Pediatrics Archie Bleyer, MD, FRCP (Glasg)
Nerissa S. Bauer, MD, MPH Stanford University School of Medicine Clinical Research Professor
Assistant Professor Director, Division of Pediatric Cardiology Knight Cancer Center
Department of General and Community Pediatrics Lucile Packard Children’s Hospital Oregon Health & Science University
Section of Children’s Health Services Research Palo Alto, California Chair, Institutional Review Board for St. Charles
Indiana University School of Medicine Cardiac Development Health System
Indianapolis, Indiana The Fetal to Neonatal Circulatory Transition Portland, Oregon;
Developmental-Behavioral Screening and History and Physical Examination Professor of Pediatrics
Surveillance Laboratory Evaluation University of Texas MD Anderson Cancer Center
Epidemiology and Genetic Basis of Congenital Heart Houston, Texas
Michelle L. Bayer, MD Disease Principles of Treatment (Cancer and Benign Tumors)
Resident Physician Evaluation and Screening of the Infant or Child with The Leukemias
Department of Dermatology Congenital Heart Disease Congenital Disorders of the Lung
Medical College of Wisconsin Acyanotic Congenital Heart Disease: Left-to-Right
Children’s Hospital of Wisconsin Shunt Lesions Steven R. Boas, MD, FAAP, FACSM
Milwaukee, Wisconsin Acyanotic Congenital Heart Disease: Obstructive Director, The Cystic Fibrosis Center of Chicago
Disorders of the Mucous Membranes Lesions President and CEO, The Cystic Fibrosis Institute
Acyanotic Congenital Heart Disease: Regurgitant Glenview, Illinois;
Richard E. Behrman, MD Lesions Clinical Associate Professor of Pediatrics
Nonprofit Healthcare and Educational Consultants Cyanotic Congenital Heart Disease: Evaluation of Northwestern University Feinberg School of
to Medical Institutions the Critically Ill Neonate with Cyanosis and Medicine
Santa Barbara, California Respiratory Distress Chicago, Illinois
Overview of Pediatrics Cyanotic Congenital Heart Lesions: Lesions Emphysema and Overinflation
Associated with Decreased Pulmonary Blood α1-Antitrypsin Deficiency and Emphysema
Michael J. Bell, MD Flow Other Distal Airway Diseases
Professor Cyanotic Congenital Heart Disease: Lesions Skeletal Diseases Influencing Pulmonary Function
Departments of Critical Care Medicine, Neurologic Associated with Increased Pulmonary Blood Flow
Surgery, and Pediatrics Other Congenital Heart and Vascular Walter O. Bockting, PhD
University of Pittsburgh School of Medicine Malformations Professor of Medical Psychology (in Psychiatry and
Director, Pediatric Neurocritical Care Pulmonary Hypertension Nursing)
Director, Pediatric Neurotrauma Center General Principles of Treatment of Congenital Heart Research Scientist, New York State Psychiatric
University of Pittsburgh Medical Center Disease Institute
Pittsburgh, Pennsylvania Infective Endocarditis Division of Gender, Sexuality, and Health
Neurologic Emergencies and Stabilization Rheumatic Heart Disease Department of Psychiatry
Heart Failure Columbia University College of Physicians and
John W. Belmont, MD, PhD Pediatric Heart and Heart-Lung Transplantation Surgeons
Professor Diseases of the Blood Vessels (Aneurysms and New York, New York
Departments of Molecular and Human Genetics, Fistulas) Sexual Identity Development
Pediatrics, and Pathology and Immunology
Baylor College of Medicine Zulfiqar Ahmed Bhutta, MBBS, PhD, Neal F. Boerkoel, MD, PhD
Houston, Texas FRCPCH, FAAP National Human Genome Research Institute
Genetics of Common Disorders Professor of Paediatrics, Nutritional Sciences, and National Institutes of Health
Public Health Bethesda, Maryland
Daniel K. Benjamin Jr., MD, PhD, University of Toronto Faculty of Medicine Genetic Approaches to Rare and Undiagnosed
MPH Robert Harding Chair in Global Child Health and Diseases
Professor of Pediatrics Policy
Division of Pediatric Infectious Diseases Co-Director, SickKids Centre for Global Child Natalija Bogdanovic, MD
Faculty Associate Director, Duke Clinical Research Health Department of Psychiatry
Institute The Hospital for Sick Children Boston Medical Center
Duke University Medical Center Toronto, Ontario, Canada; Boston, Massachusetts
Durham, North Carolina Founding Director, Centre of Excellence in Women Mood Disorders
Principles of Antifungal Therapy and Child Health
Candida The Aga Khan University, South Central Asia and Mark Boguniewicz, MD
East Africa Professor of Pediatrics
Michael J. Bennett, PhD, FRCPath, Karachi, Pakistan Division of Pediatric Allergy-Immunology
FACB Innovations in Addressing Child Health and University of Colorado School of Medicine
Professor of Pathology and Laboratory Medicine Survival in Low-Income Settings National Jewish Health
University of Pennsylvania Perelman School of Salmonella Denver, Colorado
Medicine Acute Gastroenteritis in Children Ocular Allergies
Director, Michael J. Palmieri Metabolic Disease Adverse Reactions to Drugs
Laboratory Samra S. Blanchard, MD
Children’s Hospital of Philadelphia Associate Professor of Pediatrics Daniel J. Bonthius, MD, PhD
Philadelphia, Pennsylvania University of Maryland School of Medicine Professor of Pediatrics and Neurology
Disorders of Mitochondrial Fatty Acid ß-Oxidation Baltimore, Maryland University of Iowa School of Medicine
Peptic Ulcer Disease in Children Iowa City, Iowa
Lymphocytic Choriomeningitis Virus
 Contributors ix

Brett J. Bordini Cynthia Etzler Budek, MS, APN/NP, Miguel M. Cabada, MD, MSc
Assistant Professor CPNP-AC/PC Research Associate, Tropical Medicine Institute
Department of Pediatrics Pediatric Nurse Practitioner Universidad Peruana Cayetano Heredia
Medical College of Wisconsin Department of Pulmonary and Critical Care Lima, Peru;
Pediatric Hospitalist Medicine Adjunct Instructor of Medicine
Children’s Hospital of Wisconsin Transitional Care/Pulmonary Habilitation Unit Division of Infectious Diseases
Milwaukee, Wisconsin Ann & Robert H. Lurie Children’s Hospital of University of Texas Medical Branch at Galveston
Plastic Bronchitis Chicago Galveston, Texas
Chicago, Illinois Echinococcosis (Echinococcus granulosus and
Kenneth M. Boyer, MD Chronic Severe Respiratory Insufficiency Echinococcus multilocularis)
Woman’s Board Professor and Chairman
Rush Medical College of Rush University E. Stephen Buescher, MD Derya Caglar, MD
Chicago, Illinois Professor of Pediatrics Assistant Professor
Toxoplasmosis (Toxoplasma gondii) Eastern Virginia Medical School Department of Pediatrics
Medical Director, Infection Control University of Washington School of Medicine
Amanda M. Brandow, DO, MS Medical Director, Clinical Microbiology Attending Physician
Associate Professor of Pediatrics Laboratory Division of Emergency Medicine
Division of Pediatric Hematology/Oncology Children’s Hospital of the King’s Daughters Seattle Children’s Hospital
Medical College of Wisconsin Norfolk, Virginia Seattle, Washington
Milwaukee, Wisconsin Diphtheria (Corynebacterium diphtheriae) Drowning and Submersion Injury
Polycythemia
Non-Clonal Polycythemia Supinda Bunyavanich, MD, MPH Mitchell S. Cairo, MD
Anatomy and Function of the Spleen Assistant Professor Professor
Splenomegaly Departments of Pediatrics and Genetics and Departments of Pediatrics, Medicine, Pathology,
Hyposplenism, Splenic Trauma, and Splenectomy Genomic Sciences Microbiology and Immunology and Cell
Jaffe Food Allergy Institute Biology and Anatomy
†David Branski, MD Mindich Child Heath and Development Institute New York Medical College
Professor Emeritus Ichan School of Medicine at Mount Sinai Chief, Division of Pediatric Hematology, Oncology,
The Hebrew University–Hadassah School of New York, New York and Stem Cell Transplantation
Medicine Diagnosis of Allergic Disease Maria Fareri Children’s Hospital at Westchester
Jerusalem, Israel Principles of Treatment of Allergic Disease Medical Center
Disorders of Malabsorption New York Medical College
Chronic Diarrhea Carey-Ann D. Burnham, PhD Valhalla, New York
Assistant Professor of Pathology and Immunology Lymphoma
David T. Breault, MD, PhD Assistant Professor of Pediatrics
Assistant Professor of Pediatrics Washington University School of Medicine in St. Lauren E. Camarda, MD
Harvard Medical School Louis Instructor in Pediatrics
Division of Endocrinology Medical Director, Clinical Microbiology Northwestern University Feinberg School of
Boston Children’s Hospital Barnes-Jewish Hospital Medicine
Boston, Massachusetts St. Louis, Missouri Division of Pediatric Pulmonary Medicine
Diabetes Insipidus Diagnostic Microbiology Ann & Robert H. Lurie Children’s Hospital of
Other Abnormalities of Arginine Vasopressin Chicago
Metabolism and Action Gale R. Burstein, MD, MPH Chicago, Illinois
Clinical Professor Wheezing, Bronchiolitis, and Bronchitis
William J. Britt, MD Department of Pediatrics
Charles A. Alford Professor of Pediatric Infectious State University of New York at Buffalo Bruce M. Camitta, MD
Diseases School of Medicine and Biomedical Sciences Rebecca Jean Slye Professor of Pediatrics
Professor of Pediatrics and Microbiology and Commissioner Division of Pediatric Hematology/Oncology
Neurobiology Erie County Department of Health Medical College of Wisconsin
University of Alabama Birmingham School of Buffalo, New York Midwest Children’s Cancer Center
Medicine Adolescent Physical and Social Development Milwaukee, Wisconsin
Birmingham, Alabama The Epidemiology of Adolescent Health Problems Polycythemia
Cytomegalovirus Delivery of Healthcare to Adolescents Non-Clonal Polycythemia
The Breast Anatomy and Function of the Spleen
Angela R. Bryan, MD Menstrual Problems Splenomegaly
Fellow in Pediatric Rheumatology Contraception Hyposplenism, Splenic Trauma, and Splenectomy
Duke University Health System Sexually Transmitted Infections Anatomy and Function of the Lymphatic System
Durham, North Carolina Abnormalities of Lymphatic Vessels
Juvenile Idiopathic Arthritis Amaya L. Bustinduy, MD, MPH, FAAP, Lymphadenopathy
FRCPCH
Rebecca H. Buckley, MD Paediatric Infectious Diseases Research Group Angela J.P. Campbell, MD, MPH
J. Buren Sidbury Professor of Pediatrics (PIDRG) Medical Officer
Professor of Immunology St. George’s University of London Epidemiology and Prevention Branch, Influenza
Duke University School of Medicine London, United Kingdom Division
Durham, North Carolina Schistosomiasis (Schistosoma) National Center for Immunization and Respiratory
Evaluation of Suspected Immunodeficiency Flukes (Liver, Lung, and Intestinal) Diseases
The T-, B-, and NK-Cell Systems Centers for Disease Control and Prevention
T Lymphocytes, B Lymphocytes, and Natural Killer Atlanta, Georgia
Cells Influenza Viruses
Primary Defects of Antibody Production Parainfluenza Viruses
Primary Defects of Cellular Immunity
Primary Combined Antibody and Cellular
Immunodeficiencies

†Deceased
x Contributors

Waldemar A. Carlo, MD Jennifer I. Chapman, MD Christine B. Cho, MD

Edwin M. Dixon Professor of Pediatrics Assistant Professor of Pediatrics Assistant Professor of Pediatrics
Director, Division of Neonatology George Washington University School of Medicine Division of Pediatric Allergy and Clinical
University of Alabama, Birmingham Hospital and Health Sciences Immunology
Birmingham, Alabama Program Director, Pediatric Emergency Medicine National Jewish Health
Overview of Mortality and Morbidity Fellowship University of Colorado School of Medicine
The Newborn Infant Children’s National Medical Center Denver, Colorado
High-Risk Pregnancies Washington, DC Ocular Allergies
The Fetus Principles Applicable to the Developing World Adverse Reactions to Drugs
The High-Risk Infant
Clinical Manifestations of Diseases in the Newborn Ira M. Cheifetz, MD, FCCM, FAARC Robert D. Christensen, MD
Period Professor of Pediatrics and Anesthesiology Professor and Presidential Endowed Chair
Nervous System Disorders Chief, Pediatric Critical Care Medicine Divisions of Neonatology and Hematology/
Delivery Room Emergencies Duke University School of Medicine Oncology
Respiratory Tract Disorders Chief Medical Officer, Children’s Services Department of Pediatrics
Digestive System Disorders Associate Chief Medical Officer, Duke Hospital University of Utah School of Medicine
Blood Disorders Duke Children’s Hospital Director of Neonatology Research
Genitourinary System Durham, North Carolina Intermountain Healthcare
The Umbilicus Pediatric Emergencies and Resuscitation Salt Lake City, Utah
Metabolic Disturbances Shock Development of the Hematopoietic System
The Endocrine System
Wassim Chemaitilly, MD Andrew Chu, MD
Robert B. Carrigan, MD Director, Endocrinology Division Attending Physician
Assistant Clinical Professor St. Jude Children’s Research Hospital Division of Gastroenterology
Department of Orthopaedic Surgery Memphis, Tennessee Children’s Hospital of Pittsburgh of UPMC
University of Pennsylvania Perelman School of Physiology of Puberty Pittsburgh, Pennsylvania
Medicine Disorders of Pubertal Development Superior Mesenteric Artery Syndrome (Wilkie
Pediatric Hand Surgeon Syndrome, Cast Syndrome, Arteriomesenteric
Children’s Hospital of Philadelphia Yuan-Tsong Chen, MD, PhD Duodenal Compression Syndrome)
Philadelphia, Pennsylvania Professor Ileus, Adhesions, Intussusception, and Closed-Loop
The Upper Limb Departments of Pediatrics and Genetics Obstructions
Duke University Medical Center
Mary T. Caserta, MD Durham, North Carolina Michael J. Chusid, MD
Professor of Pediatrics Defects in Metabolism of Carbohydrates Professor of Pediatrics
Division of Pediatric Infectious Diseases Chief, Pediatric Infectious Diseases
University of Rochester School of Medicine and Russell W. Chesney, MD Medical College of Wisconsin
Dentistry Le Bonheur Professor and Former Chair Medical Director, Infectious Diseases
Rochester, New York Department of Pediatrics Children’s Hospital of Wisconsin
Roseola (Human Herpesviruses 6 and 7) University of Tennessee Health Science Center Milwaukee, Wisconsin
Human Herpesvirus 8 Children’s Foundation Research Institute Infection Prevention and Control
Memphis, Tennessee Other Anaerobic Infections
Denise Casey, MD Rickets Associated with Renal Tubular Acidosis
Medical Officer Bone Structure, Growth, and Hormonal Regulation Col. Theodore J. Cieslak, MD, FAAP,
Pediatric Oncology, Neuro-Oncology, and Rare Primary Chondrodystrophy (Metaphyseal Dysplasia) FIDSA
Tumors Team Hypophosphatasia Pediatric Infectious Diseases
Office of Hematology and Oncology Products Hyperphosphatasia San Antonio Military Medical Center
Food and Drug Administration Osteoporosis Department of Pediatrics
U.S. Department of Health and Human Services Fort Sam Houston, Texas
Silver Spring, Maryland Jennifer A. Chiriboga, PhD Biologic and Chemical Terrorism
Hereditary Spherocytosis Pediatric and School Psychologist
Assistant Professor Jeff A. Clark, MD
Ellen Gould Chadwick, MD Department of Counseling, Psychology, and Associate Professor
Irene Heinz Given and John LaPorte Given Chair Special Education Department of Pediatrics
in Pediatrics Duquesne University School of Psychology Wayne State University School of Medicine
Professor and Associate Chair for Education Pittsburgh, Pennsylvania Pediatric ICU Fellowship Director
Department of Pediatrics Anxiety Disorders Children’s Hospital of Michigan
Northwestern University Feinberg School of Detroit, Michigan
Medicine Yvonne E. Chiu, MD Respiratory Distress and Failure
Associate Director, Section of Pediatric, Assistant Professor of Dermatology and Pediatrics Respiratory Pathophysiology and Regulation
Adolescent, and Maternal HIV Infection Medical College of Wisconsin
Ann & Robert H. Lurie Children’s Hospital of Milwaukee, Wisconsin Thomas G. Cleary, MD
Chicago Morphology of the Skin Professor of Pediatrics (Retired)
Chicago, Illinois Evaluation of the Patient University of Texas Health Sciences Center
Acquired Immunodeficiency Syndrome (Human Eczematous Disorders Houston, Texas
Immunodeficiency Virus) Photosensitivity Shigella
Diseases of the Epidermis Escherichia coli
Lisa J. Chamberlain, MD, MPH
Assistant Professor of Pediatrics John David Clemens, MD
Stanford University School of Medicine Director
Center for Health Policy International Vaccine Institute
Center for Primary Care and Outcomes Research Seoul, South Korea
Stanford, California International Immunization Practices
Chronic Illness in Childhood
 Contributors xi

Bria M. Coates, MD Joseph A. Congeni, MD Robert S. Daum, MD, CM

Instructor in Pediatrics Director, Sports Medicine Center Professor of Pediatrics, Microbiology, and
Northwestern University Feinberg School of Akron Children’s Hospital Molecular Medicine
Medicine Akron, Ohio; University of Chicago Pritzker School of Medicine
Division of Pediatric Critical Care Medicine Associate Professor of Pediatrics and Sports Department of Pediatric Infectious Diseases
Ann & Robert H. Lurie Children’s Hospital of Medicine The University of Chicago Medicine Comer
Chicago Northeast Ohio Medical University Children’s Hospital
Chicago, Illinois Rootstown, Ohio; Chicago, Illinois
Wheezing, Bronchiolitis, and Bronchitis Clinical Associate Professor of Pediatrics and Haemophilus influenzae
Sports Medicine
Thomas D. Coates, MD Ohio University College of Osteopathic Medicine Loren T. Davidson, MD
Professor of Pediatrics and Pathology Athens, Ohio Assistant Clinical Professor
University of Southern California Keck School of Sports-Related Traumatic Brain Injury (Concussion) Department of Physical Medicine and
Medicine Cervical Spinal Injuries Rehabilitation
Head, Section of Hematology University of California, Davis
Children’s Center for Cancer and Blood Diseases Christine M. Conroy, BS Davis, California;
Children’s Hospital of Los Angeles Villanova University Director, Spinal Cord Injury
Los Angeles, California Villanova, Pennsylvania Shriner’s Hospital for Children
Neutrophils Arthrogryposis Sacramento, California
Disorders of Phagocyte Function Spasticity
Amber R. Cooper, MD, MSCI
Joanna S. Cohen, MD Assistant Professor Richard S. Davidson, MD
Adjunct Assistant Professor of Emergency Division of Reproductive Endocrinology and Clinical Professor
Medicine Infertility Department of Orthopaedic Surgery
George Washington University School of Medicine Department of Obstetrics and Gynecology University of Pennsylvania Perelman School of
Division of Pediatric Emergency Medicine Washington University School of Medicine in St. Medicine
Children’s National Medical Center Louis Attending Orthopaedic Surgeon
Washington, DC St. Louis, Missouri Children’s Hospital of Philadelphia
Care of Abrasions and Minor Lacerations Vulvovaginal and Müllerian Anomalies Philadelphia, Pennsylvania
The Foot and Toes
Mitchell B. Cohen, MD Ronina A. Covar, MD Leg-Length Discrepancy
Professor and Chair, Department of Pediatrics Associate Professor Arthrogryposis
University of Alabama at Birmingham Department of Pediatrics
Physician-in-Chief, Children’s of Alabama National Jewish Health H. Dele Davies, MD, MS, MHCM
Birmingham, Alabama University of Colorado School of Medicine Vice-Chancellor for Academic Affairs
Clostridium difficile Infection Denver, Colorado Dean for Graduate Studies
Childhood Asthma University of Nebraska Medical Center
Michael Cohen-Wolkowiez, MD Omaha, Nebraska
Associate Professor of Pediatrics James E. Crowe Jr., MD Chancroid (Haemophilus ducreyi)
Division of Pediatric Infectious Diseases Professor of Pediatrics and Microbiology and Syphilis (Treponema pallidum)
Duke University School of Medicine Immunology Nonvenereal Treponemal Infections
Durham, North Carolina Ingram Professor of Research Leptospira
Principles of Antifungal Therapy Director, Vanderbilt Vaccine Center Relapsing Fever (Borrelia)
Vanderbilt University Medical Center
Robert A. Colbert, MD, PhD Nashville, Tennessee Najat C. Daw, MD
Deputy Clinical Director Respiratory Syncytial Virus Professor
National Institute of Arthritis and Musculoskeletal Human Metapneumovirus Division of Pediatrics
and Skin Diseases University of Texas MD Anderson Cancer Center
Chief, Pediatric Translational Branch Steve J. Czinn, MD Houston, Texas
National Institutes of Health Professor and Chair Neoplasms of the Kidney
Bethesda, Maryland Department of Pediatrics
Ankylosing Spondylitis and Other University of Maryland School of Medicine Peter S. Dayan, MD
Spondyloarthritides Baltimore, Maryland Assistant Professor of Clinical Pediatrics
Reactive and Postinfectious Arthritis Peptic Ulcer Disease in Children Columbia University College of Physicians and
Surgeons
F. Sessions Cole III, MD Josep O. Dalmau, MD, PhD Associate Director and Fellowship Director
Assistant Vice-Chancellor for Children’s Health Research Professor ICREA-IDIBAPS Division of Pediatric Emergency Medicine
Park J. White Professor of Pediatrics Department of Neurology Morgan Stanley Children’s Hospital of New
Professor of Cell Biology and Physiology Hospital Clinic York–Presbyterian
Washington University School of Medicine in St. Barcelona, Spain; New York, New York
Louis Adjunct Professor of Neurology Acute Care of the Victim of Multiple Trauma
Chief Medical Officer University of Pennsylvania Perelman School of
Vice-Chairman, Department of Pediatrics Medicine Michael R. DeBaun, MD, MPH
Director of Newborn Medicine Philadelphia, Pennsylvania Professor of Pediatrics and Medicine
St. Louis Children’s Hospital Autoimmune Encephalitis J.C. Peterson Chair in Pediatric Pulmonology
St. Louis, Missouri Vice-Chair for Clinical Research
Diffuse Lung Diseases in Childhood Toni Darville, MD Pediatrics Director, Vanderbilt-Maherry Center of
Professor of Pediatrics and Microbiology and Excellence in Sickle Cell Disease
John L. Colombo, MD Immunology Vanderbilt University
Professor of Pediatrics University of North Carolina at Chapel Hill School Nashville, Tennessee
University of Nebraska College of Medicine of Medicine Hemoglobinopathies
Division of Pediatric Pulmonology Vice-Chair for Pediatric Research
Nebraska Regional Cystic Fibrosis Center Chief, Division of Pediatric Infectious Diseases
University of Nebraska Medical Center NC Children’s Hospital
Omaha, Nebraska Chapel Hill, North Carolina
Aspiration Syndromes Neisseria gonorrhoeae (Gonococcus)
Chronic Recurrent Aspiration
xii Contributors
David R. DeMaso, MD
George P. Gardner and Olga E. Monks Professor of
Child Psychiatry
Professor of Pediatrics
Harvard Medical School
Psychiatrist-in-Chief and Chairman of Psychiatry
The Leon Eisenberg Chair in Psychiatry
Boston Children’s Hospital
Boston, Massachusetts
Assessment and Interviewing
Psychological Treatment of Children and Adolescents
Psychopharmacology
Psychotherapy
Psychiatric Hospitalization
Somatic Symptom and Related Disorders
Rumination and Pica
Motor Disorders and Habits
Mood Disorders
Suicide and Attempted Suicide
Disruptive, Impulse-Control, and Conduct Disorders
Autism Spectrum Disorder
Childhood Psychoses
Mark R. Denison, MD
Craig-Weaver Professor of Pediatrics
Division of Pediatric Infectious Disease
Vanderbilt University Medical Center
Nashville, Tennessee
Coronaviruses
Arlene E. Dent, MD, PhD
Assistant Professor of Pediatrics
Division of Infectious Diseases
Case Western Reserve University School of
Medicine
Cleveland, Ohio
Ascariasis (Ascaris lumbricoides)
Trichuriasis (Trichuris trichiura)
Enterobiasis (Enterobius vermicularis)
Strongyloidiasis (Strongyloides stercoralis)
Lymphatic Filariasis (Brugia malayi, Brugia timori,
and Wuchereria bancrofti)
Other Tissue Nematodes
Toxocariasis (Visceral and Ocular Larva Migrans)
Trichinosis (Trichinella spiralis)
Robert J. Desnick, MD, PhD
Dean for Genetics and Genomic Medicine
Professor and Chair Emeritus, Genetics and
Genomic Sciences
Professor, Departments of Pediatrics, Oncological
Sciences, and Obstetrics, Gynecology, and
Reproductive Science
Icahn School of Medicine at Mount Sinai
New York, New York
Lipidoses (Lysosomal Storage Disorders)
Mucolipidoses
Disorders of Glycoprotein Degradation and
Structure
The Porphyrias
Gabrielle A. deVeber, MD, MHSc
Professor of Paediatrics
Director, Children’s Stroke Program
University of Toronto Faculty of Medicine
Staff Neurologist
Senior Scientist, Child Health Evaluative Sciences
The Hospital for Sick Children
Toronto, Ontario, Canada
Pediatric Stroke
Anil Dhawan, MD
Consultant Paediatric Hepatologist
Pediatric Liver Centre
King’s College London School of Medicine
King’s College Hospital NSH Foundation Trust
London, United Kingdom
Liver and Biliary Disorders Causing Malabsorption
André A.S. Dick, MD, MPH, FACS Kelly A. Dougherty, PhD
Assistant Professor of Surgery Assistant Professor of Pediatrics
Division of Transplantation University of Pennsylvania Perelman School of
University of Washington School of Medicine Medicine
Division of Transplant Surgery Division of Gastroenterology, Hepatology, and
Seattle Children’s Hospital Nutrition
Seattle, Washington Children’s Hospital of Philadelphia
Intestinal Transplantation in Children with Philadelphia, Pennsylvania
Intestinal Failure Nutritional Requirements
Brianne Z. Dickey, MD Alexander Doyle, MBBS
Resident Physician HHMI Postdoctoral Research Fellow
Department of Dermatology Institute of Genetic Medicine
Medical College of Wisconsin Johns Hopkins University School of Medicine
Milwaukee, Wisconsin Baltimore, Maryland
Morphology of the Skin Marfan Syndrome
Evaluation of the Patient
Eczematous Disorders Daniel A. Doyle, MD
Photosensitivity Chief, Division of Endocrinology
Diseases of the Epidermis Alfred I. duPont Hospital for Children
Nemours Children’s Health System
Harry C. Dietz III, MD Wilmington, Delaware
Victor A. McKusick Professor of Medicine and Hormones and Peptides of Calcium Homeostasis
Genetics and Bone Metabolism
Departments of Pediatrics, Medicine, and Hypoparathyroidism
Molecular Biology and Genetics Pseudohypoparathyroidism (Albright Hereditary
Investigator, Howard Hughes Medical Institute Osteodystrophy)
Director, William S. Smilow Center for Marfan Hyperparathyroidism
Syndrome Research
Institute of Genetic Medicine Jefferson J. Doyle, MBBChir, MHS,
Johns Hopkins University School of Medicine MA
Baltimore, Maryland Postdoctoral Research Fellow
Marfan Syndrome Institute of Genetic Medicine
Johns Hopkins University School of Medicine
Lydia J. Donoghue, MD Baltimore, Maryland
Director, Trauma Center Marfan Syndrome
Children’s Hospital of Michigan
Detroit, Michigan Patrick C. Drayna, MD
Tumors of the Digestive Tract Assistant Professor of Pediatrics
Division of Pediatric Emergency Medicine
Patricia A. Donohoue, MD Medical College of Wisconsin
Professor of Pediatrics Children’s Hospital of Wisconsin
Chief, Section of Endocrinology and Diabetes Milwaukee, Wisconsin
Medical College of Wisconsin Evaluation of the Sick Child in the Office and Clinic
Program Director, Endocrine and Diabetes
Children’s Hospital of Wisconsin Stephen C. Dreskin, MD, PhD
Milwaukee, Wisconsin Professor of Medicine and Immunology
Development and Function of the Gonads Division of Allergy and Clinical Immunology
Hypofunction of the Testes Department of Medicine
Pseudoprecocity Resulting from Tumors of the Testes University of Colorado School of Medicine
Gynecomastia Aurora, Colorado
Hypofunction of the Ovaries Urticaria (Hives) and Angioedema
Pseudoprecocity Resulting from Lesions of the Ovary
Disorders of Sex Development Beth A. Drolet, MD
Professor of Dermatology
Mary K. Donovan, RN, CS, PNP Medical College of Wisconsin
Pediatric Nurse Practitioner and Care Coordinator Children’s Hospital of Wisconsin
Shriners Hospital for Children Milwaukee, Wisconsin
Shriners Burns Hospital Principles of Therapy (Skin)
Boston, Massachusetts Hyperpigmented Lesions
Burn Injuries Diseases of Subcutaneous Tissue
Cold Injuries Disorders of the Mucous Membranes
Cutaneous Bacterial Infections
John P. Dormans, MD Cutaneous Fungal Infections
Professor and The Richard M. Armstrong Jr. Cutaneous Viral Infections
Endowed Chair Arthropod Bites and Infestations
Department of Orthopaedic Surgery
University of Pennsylvania Perelman School of
Medicine
Chief, Division of Orthopaedic Surgery
Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania
Growth and Development
Evaluation of the Child
The Hip
Common Fractures

Yigal Dror, MD, FRCP(C)
Professor of Paediatrics
University of Toronto Faculty of Medicine
Head, Hematology Section Director, Marrow
Failure and Myelodysplasia Program
The Hospital for Sick Children
Toronto, Ontario, Canada
The Inherited Pancytopenias
Howard Dubowitz, MD, MS, FAAP
Professor of Pediatrics
Chief, Division of Child Protection
Director, Center for Families
Department of Pediatrics
University of Maryland School of Medicine
Baltimore, Maryland
Abused and Neglected Children
J. Stephen Dumler, MD
Professor of Pathology and Microbiology and
Immunology
University of Maryland School of Medicine
Baltimore, Maryland
Spotted Fever Group Rickettsioses
Scrub Typhus (Orientia tsutsugamushi)
Typhus Group Rickettsioses
Ehrlichioses and Anaplasmosis
Q Fever (Coxiella burnetii)
Aubrey N. Duncan, MD
Resident Physician
Department of Pediatrics
University of Rochester Medical Center
Rochester, New York
Deformational Plagiocephaly
Janet Duncan, MSN, CPNP
Department of Psychosocial Oncology and
Palliative Care
Boston Children’s Hospital
Dana-Farber Cancer Institute
Boston, Massachusetts
Pediatric Palliative Care
Paula M. Duncan, MD
Professor
Department of Pediatrics
University of Vermont College of Medicine
Burlington, Vermont
Maximizing Children’s Health: Screening,
Anticipatory Guidance, and Counseling
Jeffrey A. Dvergsten, MD
Assistant Professor of Pediatrics
Duke University School of Medicine
Division of Pediatric Rheumatology
Duke University Health System
Durham, North Carolina
Treatment of Rheumatic Diseases
Michael G. Earing, MD
Professor of Internal Medicine and Pediatrics
Division of Adult Cardiovascular Medicine and
Division of Pediatric Cardiology
Medical College of Wisconsin
Director, Wisconsin Adult Congenital Heart
Disease Program (WAtCH)
Children’s Hospital of Wisconsin
Milwaukee, Wisconsin
Congenital Heart Disease in Adults
Matthew D. Eberly, MD
Assistant Professor of Pediatrics
Uniformed Services University of the Health
Sciences
Bethesda, Maryland
Primary Amebic Meningoencephalitis
Contributors xiii
Elizabeth A. Edgerton, MD, MPH Susan Feigelman, MD
Assistant Professor Professor, Department of Pediatrics
Departments of Pediatrics and Preventive and University of Maryland School of Medicine
Community Health Baltimore, Maryland
George Washington University School of Medicine Overview and Assessment of Variability
Division of Emergency Medicine Assessment of Fetal Growth and Development
Children’s National Medical Center The First Year
Washington, DC The Second Year
Interfacility Transport of the Seriously Ill or Injured The Preschool Years
Pediatric Patient Middle Childhood
Marie E. Egan, MD Marianne E. Felice, MD
Associate Professor of Pediatrics (Respiratory) and Professor
of Cellular and Molecular Physiology Departments of Pediatrics and Obstetrics and
Director, Cystic Fibrosis Center Gynecology
Yale School of Medicine University of Massachusetts Medical School
New Haven, Connecticut Principle Investigator, National Children’s Study
Cystic Fibrosis UMass Study Center
Worcester, Massachusetts
Jack S. Elder, MD, FACS Adolescent Pregnancy
Chief of Pediatric Urology Adolescent Rape
Massachusetts General Hospital
Boston, Massachusetts Eric I. Felner, MD, MSCR
Congenital Anomalies and Dysgenesis of the Kidneys Associate Professor of Pediatrics
Urinary Tract Infections Division of Pediatric Endocrinology
Vesicoureteral Reflux Director, Pediatric Endocrinology Fellowship
Obstruction of the Urinary Tract Program
Anomalies of the Bladder Director, Pediatric Clerkships
Neuropathic Bladder Emory University School of Medicine
Enuresis and Voiding Dysfunction Atlanta, Georgia
Anomalies of the Penis and Urethra Hormones of the Hypothalamus and Pituitary
Disorders and Anomalies of the Scrotal Contents Hypopituitarism
Trauma to the Genitourinary Tract
Urinary Lithiasis Edward C. Fels, MD
Pediatric and Adult Rheumatology
Dianne S. Elfenbein, MD Rheumatology Associates, PA
Professor of Pediatrics Portland, Maine
Director, Division of Adolescent Medicine Vasculitis Syndromes
St. Louis University School of Medicine
St. Louis, Missouri Kora N. Felsch, MD
Adolescent Pregnancy Hospitalist
Cardinal Glennon Children’s Medical Center
Stephen C. Eppes, MD, FAAP St. Louis, Missouri
Professor of Pediatrics Breast Concerns
Jefferson Medical College of Thomas Jefferson
University Thomas W. Ferkol Jr., MD
Philadelphia, Pennsylvania; Alexis Hartmann Professor of Pediatrics
Director, Pediatric Infectious Diseases Director, Division of Pediatric Allergy,
Christiana Care Health System Immunology, and Pulmonary Medicine
Wilmington, Delaware Washington University School of Medicine in
Lyme Disease (Borrelia burgdorferi) St. Louis
St. Louis, Missouri
Jessica Ericson, MD Primary Ciliary Dyskinesia (Immotile Cilia
Pediatric Infectious Diseases Fellow Syndrome, Kartagener Syndrome)
Duke University Medical Center
Durham, North Carolina Can H. Ficicioglu, MD, PhD
Candida Associate Professor
Department of Pediatrics
Alessio Fasano, MD University of Pennsylvania Perelman School of
Visiting Professor of Pediatrics Medicine
Harvard Medical School Director, Newborn Metabolic Screening Program
Chief, Division of Pediatric Gastroenterology and Children’s Hospital of Philadelphia
Nutrition Philadelphia, Pennsylvania
Associate Chief, Department of Pediatrics, Basic, Phenylalanine
Clinical, and Translational Research
Director, Center for Celiac Research Jonathan D. Finder, MD
MassGeneral Hospital for Children Professor of Pediatrics
Boston, Massachusetts University of Pittsburgh School of Medicine
Celiac Disease (Gluten-Sensitive Enteropathy) Attending Pediatric Pulmonologist
Division of Pediatric Pulmonology
Children’s Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania
Bronchomalacia and Tracheomalacia
Congenital Disorders of the Lung
xiv Contributors

Kristin N. Fiorino, MD Megan Culler Freeman, PhD Sheila S. Galbraith, MD

Assistant Professor of Clinical Pediatrics
University of Pennsylvania Perelman School of
Medicine
Attending Physician
Division of Gastroenterology, Hepatology, and
Nutrition
The Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania
Motility Disorders and Hirschsprung Disease
Philip R. Fischer, MD
Professor of Pediatrics
Mayo Clinic
Rochester, Minnesota
Adult Tapeworm Infections
Cysticercosis
Echinococcosis (Echinococcus granulosus and
Echinococcus multilocularis)
Veronica H. Flood, MD
Associate Professor of Pediatrics
Division of Pediatric Hematology/Oncology
Medical College of Wisconsin
Milwaukee, Wisconsin
Hereditary Clotting Factor Deficiencies (Bleeding
Disorders)
von Willebrand Disease
Thrombocytopenia from Acquired Disorders Causing
Decreased Production
Patricia M. Flynn, MD
Deputy Clinical Director
Arthur Ashe Chair in Pediatric AIDS Research
Director, Clinical Research, Infectious Diseases
St. Jude Children’s Research Hospital
Professor of Pediatrics and Preventive Medicine
University of Tennessee College of Medicine
Memphis, Tennessee
Infection Associated with Medical Devices
Cryptosporidium, Isospora, Cyclospora, and
Microsporidia
Joel A. Forman, MD
Associate Professor of Pediatrics and Preventive
Medicine
Vice-Chair for Education
Department of Pediatrics
Icahn School of Medicine at Mount Sinai
New York, New York
Chemical Pollutants
Michael M. Frank, MD
Samuel L. Katz Professor of Pediatrics, Medicine,
and Immunology
Duke University School of Medicine
Durham, North Carolina
Urticaria (Hives) and Angioedema
Melvin H. Freedman, MD, FRCP(C),
FAAP
Professor Emeritus of Pediatrics
University of Toronto Faculty of Medicine
Honorary Consultant, Hematology/Oncology
The Hospital for Sick Children
Toronto, Ontario, Canada
The Inherited Pancytopenias
Departments of Pediatrics and Pathology,
Microbiology, and Immunology
Vanderbilt University School of Medicine
Nashville, Tennessee
Coronaviruses
Melissa J. Frei-Jones, MD, MSCI
Assistant Professor of Pediatrics
Division of Pediatric Hematology/Oncology
University of Texas Health Sciences Center
Santa Rosa Children’s Hospital
San Antonio, Texas
Hemoglobinopathies
Deborah Friedman, MD
Assistant Clinical Professor of Pediatrics
Case Western Reserve University School of
Medicine
Cleveland, Ohio
Neonatal Lupus
Erika Friehling, MD
Assistant Professor of Pediatrics
University of Pittsburgh School of Medicine
Division of Pediatric Hematology/Oncology
Children’s Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania
Principles of Diagnosis (Cancer and Benign
Tumors)
Principles of Treatment (Cancer and Benign
Tumors)
The Leukemias
Donald P. Frush, MD
Professor of Radiology
Chief, Division of Pediatric Radiology
Duke University Medical Center
Durham, North Carolina
Biologic Effects of Radiation on Children
James T. Gaensbauer, MD, MSc
Assistant Professor of Pediatrics
University of Colorado School of Medicine
Divisions of Hospital Medicine and Infectious
Diseases
Children’s Hospital Colorado
Aurora, Colorado
Staphylococcus
Sheila Gahagan, MD, MPH
Professor and Chief
Academic General Pediatrics, Child Development,
and Community Health
Martin Stein Endowed Chair, Developmental-
Behavioral Pediatrics
University of California, San Diego
La Jolla, California
Overweight and Obesity
William A. Gahl, MD, PhD
Clinical Director, National Human Genome
Research Institute
Director, NIH Undiagnosed Diseases Program
National Institutes of Health
Bethesda, Maryland
Genetic Approaches to Rare and Undiagnosed
Diseases
Associate Professor of Dermatology
Medical College of Wisconsin
Children’s Hospital of Wisconsin
Milwaukee, Wisconsin
Hypopigmented Lesions
Diseases of the Dermis
Acne
William B. Gallentine, DO
Assistant Professor of Pediatrics
Duke University School of Medicine
Division of Pediatric Neurology
Duke University Health System
Durham, North Carolina
Central Nervous System Vasculitis
Paula M. Gardiner, MD, MPH
Assistant Professor
Department of Family Medicine
Boston University School of Medicine
Assistant Director, Integrative Medicine
Boston Medical Center
Boston, Massachusetts
Complementary Therapies and Integrative Medicine
Luigi R. Garibaldi, MD
Professor of Pediatrics
University of Pittsburgh School of Medicine
Clinical Director
Division of Pediatric Endocrinology
Children’s Hospital of UPMC
Pittsburgh, Pennsylvania
Physiology of Puberty
Disorders of Pubertal Development
Gregory M. Gauthier, MD, MS
Assistant Professor of Medicine
Division of Infectious Diseases
University of Wisconsin School of Medicine
Madison, Wisconsin
Blastomycosis (Blastomyces dermatitidis)
K. Michael Gibson, PhD
Allen I. White Distinguished Professor and Chair
Experimental and Systems Pharmacology
Washington State University College of
Pharmacology
Spokane, Washington
Genetic Disorders of Neurotransmitters
Mark Gibson, MD
Professor (Clinical) Emeritus
Department of Obstetrics and Gynecology
Chief, Division of Reproductive Endocrinology
University of Utah School of Medicine
Salt Lake City, Utah
Polycystic Ovary Syndrome and Hirsutism
Francis Gigliotti, MD
Professor of Pediatrics and Microbiology and
Immunology
Lindsey Distinguished Professor for Pediatric
Research
University of Rochester School of Medicine and
Dentistry
Division of Pediatric Infectious Diseases
University of Rochester Medical Center
Rochester, New York
Pneumocystis jiroveci (Pneumocystis carinii)
 Contributors xv

Walter S. Gilliam, MSEd, PhD Leslie B. Gordon, MD, PhD Larry A. Greenbaum, MD, PhD
Associate Professor Associate Professor of Pediatrics Research Marcus Professor of Pediatrics
Department of Psychology Warren Alpert Medical School of Brown University Director, Division of Pediatric Nephrology
Child Study Center Providence, Rhode Island; Emory University School of Medicine
Director, The Edward Zigler Center in Child Department of Anesthesia Children’s Healthcare of Atlanta
Development and Social Policy Boston Children’s Hospital Atlanta, Georgia
Yale School of Medicine Harvard Medical School Rickets and Hypervitaminosis D
New Haven, Connecticut Boston, Massachusetts; Vitamin E Deficiency
Childcare: How Pediatricians Can Support Children Medical Director, The Progeria Research Vitamin K Deficiency
and Families Foundation Micronutrient Mineral Deficiencies
Peabody, Massachusetts Electrolyte and Acid-Base Disorders
Salil Ginde, MD, MPH Hutchinson-Gilford Progeria Syndrome Maintenance and Replacement Therapy
Assistant Professor of Pediatrics Deficit Therapy
Division of Pediatric Cardiology Marc H. Gorelick, MD, MSCE Fluid and Electrolyte Treatment of Specific Disorders
Medical College of Wisconsin Professor of Pediatrics
Milwaukee, Wisconsin Medical College of Wisconsin Anne G. Griffiths, MD
Congenital Heart Disease in Adults Children’s Hospital of Wisconsin Instructor in Pediatrics
Milwaukee, Wisconsin Northwestern University Feinberg School of
Charles M. Ginsburg, MD Evaluation of the Sick Child in the Office and Clinic Medicine
Senior Associate Dean for Academic Hospitalist, Neonatal Intensive Care Unit
Administration Jane M. Gould, MD, FAAP Ann & Robert H. Lurie Children’s Hospital of
Professor of Pediatrics Associate Professor of Pediatrics Chicago
Marilyn R. Corrigan Distinguished Chair in Drexel University College of Medicine Chicago, Illinois
Pediatric Research Attending Physician, Infectious Diseases Chronic or Recurrent Respiratory Symptoms
University of Texas Southwestern Medical Center St. Christopher’s Hospital for Children
Houston, Texas Philadelphia, Pennsylvania Allison Grimes, MD
Animal and Human Bites Cryptococcus neoformans Fellow in Pediatric Hematology/Oncology
Histoplasmosis (Histoplasma capsulatum) University of Texas Health Sciences Center
John A. Girotto, MD, MMA, FAAP, Paracoccidioides brasiliensis San Antonio, Texas
FACS Zygomycosis (Mucormycosis) Abnormal Hemoglobins Causing Cyanosis
Associate Professor of Pediatrics, Neurosurgery, Hereditary Methemoglobinemia
and Plastic and Reconstructive Surgery Olivier Goulet, MD Hereditary Methemoglobinemia with Deficiency of
Director, Cleft and Craniofacial Anomalies Center Professor of Pediatrics NADH Cytochrome B5 Reductase
Golisano Children’s Hospital at Strong University of Paris V—René Descartes
University of Rochester Medical Center Head, Division of Pediatric Gastroenterology- Natalia M. Grindler, MD
Rochester, New York Hepatology and Nutrition Resident Physician
Deformational Plagiocephaly Hôpital Necker-Enfants Malades/AP-HP Department of Obstetrics and Gynecology
Paris, France Washington University School of Medicine in St.
Lisa Giulino-Roth, MD Other Malabsorptive Syndromes Louis
Assistant Professor of Pediatrics St. Louis, Missouri
Division of Pediatric Hematology/Oncology Deanna M. Green, MD, MHS Vulvovaginal and Müllerian Anomalies
Weill Cornell Medical College Assistant Professor of Pediatrics
New York, New York Division of Pediatric Pulmonary and Sleep Kenneth L. Grizzle, PhD
Lymphoma Medicine Associate Professor
Duke University School of Medicine Child Development Center—Brookfield
Frances Page Glascoe, PhD Durham, North Carolina Medical College of Wisconsin
Professor Cystic Fibrosis Brookfield, Wisconsin
Department of Pediatrics Childhood-Onset Fluency Disorder: Dysfluency
Vanderbilt University School of Medicine Michael Green, MD, MPH (Stuttering, Stammering)
Nashville, Tennessee Professor of Pediatrics and Surgery
Developmental-Behavioral Screening and University of Pittsburgh School of Medicine Veronique Groleau, MD
Surveillance Division of Pediatric Infectious Diseases Fellow
Children’s Hospital of Pittsburgh of UPMC Division of Gastroenterology, Hepatology, and
Denise M. Goodman, MD, MS Pittsburgh, Pennsylvania Nutrition
Professor Infections in Immunocompromised Persons Children’s Hospital of Philadelphia
Department of Pediatrics Philadelphia, Pennsylvania
Northwestern University Feinberg School of Thomas P. Green, MD Nutritional Requirements
Medicine Founders’ Board Centennial Professor and Chair Feeding Healthy Infants, Children, and Adolescents
Ann & Robert H. Lurie Children’s Hospital of Department of Pediatrics
Chicago Northwestern University Feinberg School of Andrew B. Grossman, MD
Chicago, Illinois Medicine Assistant Professor of Clinical Pediatrics
Wheezing, Bronchiolitis, and Bronchitis Physician-in-Chief University of Pennsylvania Perelman School of
Ann & Robert H. Lurie Children’s Hospital of Medicine
Alison Gopnik, PhD Chicago Co-Director, Center for Pediatric Inflammatory
Professor of Psychology and Affiliate Professor of Chicago, Illinois Bowel Disease
Philosophy Diagnostic Approach to Respiratory Disease The Children’s Hospital of Philadelphia
University of California at Berkeley Chronic or Recurrent Respiratory Symptoms Philadelphia, Pennsylvania
Berkeley, California Pulmonary Edema Inflammatory Bowel Disease
Cognitive Development: Domains and Theories
xvi Contributors

David C. Grossman, MD, MPH Scott B. Halstead, MD Lindsay A. Hatzenbuehler, MD, MPH
Senior Investigator Group Health Research Professor of Pediatrics and Medical Genetics Pediatric Infectious Diseases Fellow
Institute University of British Columbia Faculty of Medicine Baylor College of Medicine
Professor of Health Services British Columbia’s Children’s Hospital Texas Children’s Hospital
University of Washington School of Public Health Vancouver, British Columbia, Canada Houston, Texas
Adjunct Professor of Pediatrics Arboviral Infections in North America Tuberculosis (Mycobacterium tuberculosis)
University of Washington School of Medicine Arboviral Infections Outside North America
Seattle, Washington Dengue Fever and Dengue Hemorrhagic Fever Fern R. Hauck, MD, MS
Injury Control Yellow Fever Spencer P. Bass MD Twenty-First Century
Ebola and Other Viral Hemorrhagic Fevers Professor of Family Medicine
Alfredo Guarino, MD Hantavirus Pulmonary Syndrome Departments of Family Medicine and Public
Professor Health Sciences
Department of Pediatrics Margaret R. Hammerschlag, MD Director, International Family Medicine Clinic
University of Naples Federico II Professor of Pediatrics and Medicine University of Virginia School of Medicine
Napoli, Italy Director, Division of Pediatric Infectious Diseases Charlottesville, Virginia
Chronic Diarrhea SUNY Down State Medical Center Sudden Infant Death Syndrome
Brooklyn, New York
Reut Gurion, DO Chlamydia (Chlamydophila) pneumoniae Fiona P. Havers, MD, MHS
Pediatric Rheumatology Fellow Chlamydia trachomatis Epidemic Intelligence Service Office
Division of Rheumatology Psittacosis (Chlamydia psittaci) Epidemiology and Prevention Branch, Influenza
University Hospitals Case Medical Center Division
Rainbow Babies & Children’s Hospital Aaron Hamvas, MD National Center for Immunization and Respiratory
Cleveland, Ohio Raymond and Hazel Speck Barry Professor of Diseases
Miscellaneous Conditions Associated with Arthritis Neonatology Centers for Disease Control and Prevention
Head, Division of Neonatology Atlanta, Georgia
Lisa R. Hackney, MD Ann & Robert H. Lurie Children’s Hospital of Influenza Viruses
Assistant Professor of Pediatrics Chicago
Division of Pediatric Hematology/Oncology Northwestern University Feinberg School of Jacqueline T. Hecht, PhD
Cleveland Clinic Foundation Medicine Professor and Division Head
Cleveland, Ohio Chicago, Illinois Leah L. Lewis Distinguished Chair
Hereditary Stomatocytosis Diffuse Lung Diseases in Childhood Pediatric Research Center
Glucose-6-Phosphate Dehydrogenase Deficiency and Vice-Chair for Research
Related Deficiencies Abeer J. Hani, MD Department of Pediatrics
Resident Physician UT Health Medical School of Houston
Gabriel G. Haddad, MD Division of Pediatric Neurology Associate Dean for Research
Distinguished Professor and Chair Duke University Medical Center UT Health School of Dentistry
Department of Pediatrics Durham, North Carolina Houston, Texas
University of California, San Diego Seizures in Childhood General Considerations (Bone and Joint Disorders)
Physician-in-Chief Disorders Involving Cartilage Matrix Proteins
Chief Scientific Officer James C. Harris, MD Disorders Involving Transmembrane Receptors
Rady Children’s Hospital Professor of Pediatrics, Psychiatry and Behavioral Disorders Involving Ion Transporters
San Diego, California Sciences, Mental Health, and History of Disorders Involving Transcription Factors
Diagnostic Approach to Respiratory Disease Medicine Disorders Involving Defective Bone Resorption
Division of Child and Adolescent Psychiatry Disorders for Which Defects Are Poorly Understood
Joseph Haddad Jr., MD Director, Developmental Neuropsychiatry or Unknown
Howard W. Smith Professor and Interim Chair Johns Hopkins University School of Medicine
Lawrence Savetsky Professor Baltimore, Maryland Sabrina M. Heidemann, MD
Department of Otolaryngology—Head and Neck Disorders of Purine and Pyrimidine Metabolism Professor
Surgery Department of Pediatrics
Columbia University College of Physicians and Mary E. Hartman, MD, MPH Wayne State University School of Medicine
Surgeons Assistant Professor of Pediatrics Director, Intensive Care Unit
Director, Pediatric Otolaryngology—Head and Washington University in St. Louis Co-Director of Transport
Neck Surgery Pediatric Critical Care Medicine Children’s Hospital of Michigan
New York-Presbyterian Morgan Stanley Children’s St. Louis Children’s Hospital Detroit, Michigan
Hospital St. Louis, Missouri Respiratory Pathophysiology and Regulation
New York, New York Pediatric Emergencies and Resuscitation
Congenital Disorders of the Nose J. Owen Hendley, MD
Acquired Disorders of the Nose David B. Haslam, MD Professor
Nasal Polyps Associate Professor of Pediatrics Department of Pediatrics
General Considerations and Evaluation (Ear) University of Cincinnati College of Medicine University of Virginia School of Medicine
Hearing Loss Director, Antimicrobial Stewardship Program Charlottesville, Virginia
Congenital Malformations Clinical Director, Division of Infectious Diseases Sinusitis
External Otitis (Otitis Externa) Cincinnati Children’s Hospital Medical Center Retropharyngeal Abscess, Lateral Pharyngeal
The Inner Ear and Diseases of the Bony Labyrinth Cincinnati, Ohio (Parapharyngeal) Abscess, and Peritonsillar
Traumatic Injuries of the Ear and Temporal Bone Non–Group A or B Streptococci Cellulitis/Abscess
Tumors of the Ear and Temporal Bone Enterococcus
Frederick M. Henretig, MD
Joseph F. Hagan Jr., MD H. Hesham Abdel-Kader Hassan, MD Division of Emergency Medicine
Clinical Professor Professor of Pediatrics Children’s Hospital of Philadelphia
Department of Pediatrics Chief, Division of Pediatric Gastroenterology and Professor Emeritus of Pediatrics
University of Vermont College of Medicine Nutrition Perelman School of Medicine
Hagan, Rinehart, and Connolly Pediatricians, The University of Arizona College of Medicine University of Pennsylvania
PLLC Tucson, Arizona Philadelphia, Pennsylvania
Burlington, Vermont Cholestasis Biologic and Chemical Terrorism
Maximizing Children’s Health: Screening,
Anticipatory Guidance, and Counseling
 Contributors xvii

Gloria P. Heresi, MD Jeffrey D. Hord, MD Stephen A. Huang, MD

Professor of Pediatrics Director, Showers Family Center for Childhood Assistant Professor of Pediatrics
Director, Division of Pediatric Infectious Diseases Cancer and Blood Disorders Harvard Medical School
University of Texas Health Sciences Center Associate Chair of Pediatrics for Subspecialty Director, Thyroid Program
Houston, Texas Practices Division of Endocrinology
Campylobacter Akron Children’s Hospital Boston Children’s Hospital
Yersinia Akron, Ohio Boston, Massachusetts
Aeromonas and Plesiomonas The Acquired Pancytopenias Thyroid Development and Physiology
Defects of Thyroxine-Binding Globulin
Andrew D. Hershey, MD, PhD, FAHS B. David Horn, MD Hypothyroidism
Professor of Pediatrics and Neurology Assistant Professor Thyroiditis
University of Cincinnati College of Medicine Department of Orthopaedic Surgery Goiter
Endowed Chair, Division of Neurology University of Pennsylvania Perelman School of Hyperthyroidism
Cincinnati Children’s Hospital Medical Center Medicine Carcinoma of the Thyroid
Cincinnati, Ohio Attending Orthopaedic Surgeon
Headaches Children’s Hospital of Philadelphia Heather G. Huddleston, MD
Philadelphia, Pennsylvania Assistant Professor
Cynthia E. Herzog, MD The Hip Department of Obstetrics, Gynecology, and
Professor of Pediatrics Reproductive Sciences
University of Texas MD Anderson Cancer Center Helen M. Horstmann, MD University of California, San Francisco School of
Houston, Texas Associate Professor Medicine
Retinoblastoma Department of Orthopaedic Surgery San Francisco, California
Gonadal and Germ Cell Neoplasms University of Pennsylvania Perelman School of Polycystic Ovary Syndrome and Hirsutism
Neoplasms of the Liver Medicine
Benign Vascular Tumors Attending Physician Vicki Huff, PhD
Melanoma Children’s Hospital of Philadelphia Professor
Nasopharyngeal Carcinoma Philadelphia, Pennsylvania Department of Molecular Genetics/Cancer
Adenocarcinoma of the Colon and Rectum Arthrogryposis Genetics
Desmoplastic Small Round Cell Tumor University of Texas MD Anderson Cancer Center
William A. Horton, MD Houston, Texas
Jessica Hochberg, MD Professor Neoplasms of the Kidney
Assistant Professor of Pediatrics Department of Molecular Medical Genetics
Division of Pediatric Hematology, Oncology, and Oregon Health & Science University Denise Hug, MD
Stem Cell Transplant Director of Research Associate Professor
New York Medical College Shriners Hospitals for Children Department of Ophthalmology
Maria Fareri Children’s Hospital at Westchester Portland, Oregon University of Missouri—Kansas City School of
Medical Center General Considerations (Bone and Joint Disorders) Medicine
Valhalla, New York Disorders Involving Cartilage Matrix Proteins Children’s Mercy Hospital
Lymphoma Disorders Involving Transmembrane Receptors Kansas City, Missouri
Disorders Involving Ion Transporters Growth and Development (Eye)
Holly R. Hoefgen, MD Disorders Involving Transcription Factors Examination of the Eye
Fellow, Department of Obstetrics and Gynecology Disorders Involving Defective Bone Resorption Abnormalities of Refraction and Accommodation
Washington University School of Medicine in St. Disorders for Which Defects Are Poorly Understood Disorders of Vision
Louis or Unknown Abnormalities of Pupil and Iris
St. Louis, Missouri Disorders of Eye Movement and Alignment
Vulvovaginitis Peter J. Hotez, MD, PhD, FASTMH, Abnormalities of the Lids
FAAP Disorders of the Lacrimal System
Lauren D. Holinger, MD, FAAP, FACS Founding Dean, National School of Tropical Disorders of the Conjunctiva
Paul H. Holinger MD Professor and Interim Head, Medicine Abnormalities of the Cornea
Division of Otolaryngology Professor of Pediatrics and Molecular Virology and Abnormalities of the Lens
Department of Pediatrics Microbiology Disorders of the Uveal Tract
Northwestern University Feinberg School of Baylor College of Medicine Disorders of the Retina and Vitreous
Medicine Endowed Chair in Tropical Pediatrics Abnormalities of the Optic Nerve
Ann & Robert H. Lurie Children’s Hospital of Texas Children’s Hospital Childhood Glaucoma
Chicago Houston, Texas Orbital Abnormalities
Chicago, Illinois Hookworms (Necator americanus and Ancylostoma Orbital Infections
Congenital Anomalies of the Larynx, Trachea, and spp.) Injuries to the Eye
Bronchi
Foreign Bodies in the Airway Evelyn Hsu, MD Dennis P.M. Hughes, MD, PhD
Laryngotracheal Stenosis and Subglottic Stenosis Assistant Professor of Pediatrics Associate Professor of Pediatrics
Neoplasms of the Larynx, Trachea, and Bronchi Seattle Children’s Hospital University of Texas MD Anderson Cancer Center
Seattle, Washington Houston, Texas
Cynthia Holland-Hall, MD, MPH Liver Transplantation Melanoma
Associate Clinical Professor of Clinical Pediatrics
The Ohio State University College of Medicine Winston W. Huh, MD
Section of Adolescent Medicine Assistant Professor of Pediatrics
Nationwide Children’s Hospital University of Texas MD Anderson Cancer Center
Columbus, Ohio Houston, Texas
Adolescent Physical and Social Development Gonadal and Germ Cell Neoplasms
Transitioning to Adult Care Adenocarcinoma of the Colon and Rectum
The Breast
xviii Contributors

Stephen R. Humphrey, MD Tara Jatlaoui, MD, MPH Bridgette L. Jones, MD

Resident Physician Research Assistant Professor Associate Professor of Pediatrics
Department of Dermatology Department of Obstetrics and Gynecology Division of Allergy, Asthma, and Immunology
Medical College of Wisconsin The University of North Carolina at Chapel Hill University of Missouri—Kansas City School of
Children’s Hospital of Wisconsin Guest Researcher, Division of Reproductive Health Medicine
Milwaukee, Wisconsin Centers for Disease Control and Prevention Section of Clinical Pharmacology and Medical
Principles of Therapy (Skin) Atlanta, Georgia Toxicology
Contraception Children’s Mercy Hospitals and Clinics
David A. Hunstad, MD Kansas City, Missouri
Associate Professor of Pediatrics and Molecular M. Kyle Jensen, MD Principles of Drug Therapy
Microbiology Assistant Professor of Pediatrics
Washington University School of Medicine in St. University of Utah School of Medicine James F. Jones, MD
Louis Division of Pediatric Gastroenterology Research Medical Officer
St. Louis, Missouri Primary Children’s Hospital Viral Exanthems and Herpesvirus Branch
Animal and Human Bites Salt Lake City, Utah Division of Viral and Rickettsial Diseases
Viral Hepatitis National Center for Infectious Diseases
Carl E. Hunt, MD Centers for Disease Control and Prevention
Research Professor of Pediatrics Hal B. Jenson, MD, MBA Atlanta, Georgia
Uniformed Services University of the Health Founding Dean Chronic Fatigue Syndrome
Sciences Professor, Department of Pediatric and Adolescent
Division of Neonatology Medicine Marsha Joselow, MSW, LICSW
Walter Reed National Military Medical Center Western Michigan University Department of Psychosocial Oncology and
Bethesda, Maryland; Homer Stryker M.D. School of Medicine Palliative Care
Adjunct Professor of Pediatrics Kalamazoo, Michigan Boston Children’s Hospital
George Washington University School of Medicine Chronic Fatigue Syndrome Dana-Farber Cancer Institute
Washington, DC Epstein-Barr Virus Boston, Massachusetts
Sudden Infant Death Syndrome Human T-Lymphotropic Viruses (1 and 2) Pediatric Palliative Care

Anna K. Hunter, MD Chandy C. John, MD, MS Nicholas Jospe, MD

Assistant Clinical Professor of Pediatrics Ryan White Professor of Pediatrics Professor of Pediatrics
University of California, San Francisco Professor of Pediatrics, Microbiology and Division of Pediatric Endocrinology
UCSF Fresno Center for Medical Education and Immunology Golisano Children’s Hospital
Research Director, Ryan White Center for Pediatric University of Rochester Medical Center
Fresno, California; Infectious Diseases and Global Health Rochester, New York
Pediatric Gastroenterologist Indiana University School of Medicine Diabetes Mellitus
Children’s Hospital Central California Riley Hospital for Children at Indiana University
Madera, California Health Joel C. Joyce, MD
Pyloric Stenosis and Other Congenital Anomalies of Indianapolis, Indiana Pediatric Dermatology
the Stomach Health Advice for Children Traveling Internationally NorthShore University HealthSystem
Giardiasis and Balantidiasis Skokie, Illinois;
Stacey S. Huppert, PhD Malaria (Plasmodium) Clinician Educator
Associate Professor of Pediatrics University of Chicago Pritzker School of Medicine
University of Cincinnati College of Medicine Collin C. John, MD, MPH, FAAP Chicago, Illinois
Division of Gastroenterology, Hepatology, and Assistant Professor of Internal Medicine and Vesiculobullous Disorders
Nutrition Pediatrics Nutritional Dermatoses
Division of Developmental Biology Medical Director, West Virginia Birth Score
Cincinnati Children’s Hospital Medical Center Program Anna M. Juern, MD
Cincinnati, Ohio West Virginia University School of Medicine Division of Pediatric Dermatology
Morphogenesis of the Liver and Biliary System Morgantown, West Virginia Medical College of Wisconsin
Disorders of Lipoprotein Metabolism and Transport Milwaukee, Wisconsin
Patricia I. Ibeziako, MD Hyperpigmented Lesions
Assistant Professor of Psychiatry Michael V. Johnston, MD Cutaneous Bacterial Infections
Harvard Medical School Professor of Neurology, Pediatrics, and Physical Cutaneous Fungal Infections
Director, Psychiatry Consultation Service Medicine and Rehabilitation Cutaneous Viral Infections
Boston Children’s Hospital Johns Hopkins University School of Medicine Arthropod Bites and Infestations
Boston, Massachusetts Kennedy Krieger Institute
Somatic Symptom and Related Disorders Baltimore, Maryland Marielle A. Kabbouche, MD
Congenital Anomalies of the Central Nervous System Associate Professor of Pediatrics and Neurology
Samar H. Ibrahim, MBChB Encephalopathies University of Cincinnati College of Medicine
Assistant Professor of Pediatrics Division of Neurology
Division of Pediatric Gastroenterology and Richard B. Johnston Jr., MD Cincinnati Children’s Hospital Medical Center
Hepatology Professor of Pediatrics Cincinnati, Ohio
Mayo Clinic Associate Dean for Research Development Headaches
Rochester, Minnesota University of Colorado School of Medicine
Mitochondrial Hepatopathies Aurora, Colorado; Linda Kaljee, PhD, MAA
National Jewish Health Associate Professor
Richard F. Jacobs, MD, FAAP Denver, Colorado Department of Pediatrics
Robert H. Fiser Jr. MD Endowed Chair in Monocytes, Macrophages, and Dendritic Cells Prevention Research Center
Pediatrics The Complement System Wayne State University School of Medicine
Professor and Chair, Department of Pediatrics Disorders of the Complement System Detroit, Michigan
University of Arkansas for Medical Sciences Cultural Issues in Pediatric Care
Pediatrician-in-Chief
Arkansas Children’s Hospital
Little Rock, Arkansas
Actinomyces
Nocardia
Tularemia (Francisella tularensis)
Brucella
 Contributors xix

Deepak Kamat, MD, PhD, FAAP Virginia A. Keane, MD Judith R. Kelsen, MD

Professor and Vice-Chair of Education Associate Professor Assistant Professor of Pediatrics
Department of Pediatrics Department of Pediatrics University of Pennsylvania Perelman School of
Wayne State University School of Medicine University of Maryland School of Medicine Medicine
Designated Institutional Official Baltimore, Maryland Attending Physician
Children’s Hospital of Michigan Assessment of Growth Division of Gastroenterology, Hepatology, and
Detroit, Michigan Nutrition
Fever Gregory L. Kearns, PharmD, PhD The Children’s Hospital of Philadelphia
Fever Without a Focus Marion Merrell Dow / Missouri Chair of Medical Philadelphia, Pennsylvania
Research Foreign Bodies and Bezoars
Alvina R. Kansra, MD Professor of Pediatrics and Pharmacology
Assistant Professor of Pediatrics University of Missouri—Kansas City School of Kathi J. Kemper, MD, MPH
Medical College of Wisconsin Medicine Director, OSU Center for Integrative Health and
Division of Endocrinology Chief Scientific Officer and Chairman, Research Wellness
Children’s Hospital of Wisconsin Development and Clinical Investigation Professor of Pediatrics, Nursing, and Health and
Milwaukee, Wisconsin Associate Chair, Department of Pediatrics Rehabilitation Sciences
Hypofunction of the Ovaries Director, Pediatric Trial Network Ohio State University Wexner Medical Center
Pseudoprecocity Resulting from Lesions of the Ovary Children’s Mercy Hospitals and Clinics Nationwide Children’s Hospital
Kansas City, Missouri; Columbus, Ohio
Sheldon L. Kaplan, MD Clinical Professor of Pediatrics Complementary Therapies and Integrative Medicine
Professor and Vice-Chair for Clinical Affairs University of Kansas School of Medicine
Department of Pediatrics Kansas City, Kansas Melissa Kennedy, MD
Baylor College of Medicine Principles of Drug Therapy Attending Physician
Head, Department of Pediatric Medicine Division of Gastroenterology, Hepatology, and
Chief, Section of Infectious Disease Sarah E. Keesecker, MD Nutrition
Texas Children’s Hospital Postdoctoral Residency Fellow The Children’s Hospital of Philadelphia
Houston, Texas Department of Otolaryngology—Head and Neck Philadelphia, Pennsylvania
Osteomyelitis Surgery Malrotation
Septic Arthritis Columbia University College of Physicians and Meckel Diverticulum and Other Remnants of the
Surgeons Omphalomesenteric Duct
Aaron M. Karlin, MD New York, New York Intussusception
Clinical Associate Professor Congenital Disorders of the Nose Malformations
Department of Physical Medicine and Acquired Disorders of the Nose Ascites
Rehabilitation Nasal Polyps
Louisiana State University School of Medicine General Considerations and Evaluation (Ear) Eitan Kerem, MD
Section Head, Pediatric Rehabilitation Hearing Loss Professor and Chair
Ochsner Clinic Medical Center Congenital Malformations Department of Pediatrics
Ochsner Children’s Health Center External Otitis (Otitis Externa) Hadassah University Medical Center
New Orleans, Louisiana The Inner Ear and Diseases of the Bony Labyrinth Jerusalem, Israel
Management of Musculoskeletal Injury Traumatic Injuries of the Ear and Temporal Bone Effects of War on Children
Specific Sports and Associated Injuries Tumors of the Ear and Temporal Bone
Joseph E. Kerschner, MD, FACS,
Daniel L. Kastner, MD, PhD Desmond P. Kelly, MD FAAP
Scientific Director Professor of Clinical Pediatrics Professor of Pediatrics
National Human Genome Research Institute Vice-Chair for Academics, Department of Dean and Executive Vice-President
Distinguished Investigator Pediatrics Medical College of Wisconsin
Medical Genetics Branch University of South Carolina School of Medicine Milwaukee, Wisconsin
National Institutes of Health Greenville Otitis Media
Bethesda, Maryland Greenville, South Carolina
Hereditary Periodic Fever Syndromes and Other Neurodevelopmental Function and Dysfunction in Seema Khan, MD
Systemic Autoinflammatory Diseases the School-Age Child Associate Professor of Pediatrics
George Washington University School of Medicine
Emily R. Katz, MD Kevin J. Kelly, MD and Health Sciences
Clinical Assistant Professor Professor of Pediatrics Division of Gastroenterology and Nutrition
Department of Psychiatry and Human Behavior Division of Pediatric Allergy, Immunology, and Children’s National Medical Center
Brown University Alpert Medical School Rheumatology Washington, DC
Director, Consultation Liaison Service University of North Carolina School of Medicine Embryology, Anatomy, and Function of the
Hasbro Children’s Hospital Vice-Chair, Clinical Operations Esophagus
Providence, Rhode Island Pediatrician-in-Chief Congenital Anomalies: Esophageal Atresia and
Rumination and Pica North Carolina Children’s Hospital Tracheoesophageal Fistula
Chapel Hill, North Carolina Obstructing and Motility Disorders of the Esophagus
James W. Kazura, MD Immune and Inflammatory Lung Disease Dysmotility
Professor of Medicine in International Health Hiatal Hernia
Division of Geographic Medicine Matthew S. Kelly, MD, MPH Gastroesophageal Reflux Disease
Case Western Reserve University School of Pediatric Global Health Fellow Eosinophilic Esophagitis and Non–Gastroesophageal
Medicine Children’s Hospital of Philadelphia Reflux Disease Esophagitis
Cleveland, Ohio Philadelphia, Pennsylvania; Esophageal Perforation
Ascariasis (Ascaris lumbricoides) Princess Marina Hospital Esophageal Varices
Trichuriasis (Trichuris trichiura) Gaborone, Botswana, Africa Ingestions
Enterobiasis (Enterobius vermicularis) Community-Acquired Pneumonia
Strongyloidiasis (Strongyloides stercoralis) Jennifer S. Kim, MD
Lymphatic Filariasis (Brugia malayi, Brugia timori, Assistant Professor of Pediatrics
and Wuchereria bancrofti) Jaffe Food Allergy Institute
Other Tissue Nematodes Icahn School of Medicine at Mount Sinai
Toxocariasis (Visceral and Ocular Larva Migrans) New York, New York
Trichinosis (Trichinella spiralis) Diagnosis of Allergic Disease
Principles of Treatment of Allergic Disease
xx Contributors

Charles H. King, MD Robert M. Kliegman, MD Elliot J. Krane, MD, FAAP

Professor of International Health Professor and Chairman Emeritus Professor of Pediatrics, and Anesthesiology,
Center for Global Health and Diseases Department of Pediatrics Perioperative, and Pain Medicine
Case Western Reserve University School of Medical College of Wisconsin Stanford University School of Medicine
Medicine Children’s Hospital of Wisconsin Chief, Pediatric Pain Management
Cleveland, Ohio Milwaukee, Wisconsin Stanford Children’s Health
Schistosomiasis (Schistosoma) Refeeding Syndrome Lucile Packard Children’s Hospital at Stanford
Flukes (Liver, Lung, and Intestinal) Liver Abscess Stanford, California
Generalized Arterial Calcification of Infancy/ Pediatric Pain Management
Stephen L. Kinsman, MD Idiopathic Infantile Arterial Calcification
Associate Professor of Pediatrics Arterial Calcifications Caused by Deficiency of Peter J. Krause, MD
Division of Pediatric Neurology CD73 Senior Research Scientist
Medical University of South Carolina Female Genital Mutilation/Cutting Department of Epidemiology and Microbial
Charleston, South Carolina Reflex Seizures (Stimulus Precipitated Seizures) Diseases
Congenital Anomalies of the Central Nervous System Nodding Syndrome Yale School of Public Health
Department of Medicine and Department of
Adam Kirton, MD, MSc, FRCPC William C. Koch, MD, FAAP, FIDSA Pediatrics
Associate Professor of Pediatrics and Clinical Associate Professor of Pediatrics Yale School of Medicine
Neurosciences Medical College of Virginia / Virginia New Haven, Connecticut
University of Calgary Faculty of Medicine Commonwealth University Babesiosis (Babesia)
Director, Calgary Pediatric Stroke Program Richmond, Virginia
Alberta Children’s Hospital Research Institute Parvoviruses Richard E. Kreipe, MD, FACCP,
Calgary, Alberta, Canada FSAHM, FAED
Pediatric Stroke Patrick M. Kochanek, MD, MCCM Dr. Elizabeth R. McArnarney Professor in
Ake N. Grenvik Professor of Critical Care Pediatrics funded by Roger and Carolyn
Priya S. Kishnani, MD, MBBS Medicine Friedlander
C.L. and Sue Chen Professor of Pediatrics Vice-Chairman, Department of Critical Care Division of Adolescent Medicine
Chief, Division of Medical Genetics Medicine University of Rochester School of Medicine
Duke University Medical Center Professor of Anesthesiology, Pediatrics, Golisano Children’s Hospital
Durham, North Carolina Bioengineering, and Clinical and Translational Medical Director, Western New York
Defects in Metabolism of Carbohydrates Science Comprehensive Care Center for Eating
Director, Safar Center for Resuscitation Research Disorders
Robert L. Kitts, MD University of Pittsburgh School of Medicine Rochester, New York
Assistant Professor of Psychiatry Pittsburgh, Pennsylvania Eating Disorders
Harvard Medical School Neurologic Emergencies and Stabilization
Director, Child and Adolescent Psychiatry Steven E. Krug, MD
Fellowship Eric Kodish, MD Professor of Pediatrics
Boston Children’s Hospital Professor and Chairman Division of Pediatric Emergency Medicine
Boston, Massachusetts Department of Bioethics Northwestern University Feinberg School of
Rumination and Pica The Cleveland Clinic Foundation Medicine
Cleveland, Ohio Ann & Robert H. Lurie Children’s Hospital of
Martin B. Kleiman, MD Ethics in Pediatric Care Chicago
Ryan White Professor of Pediatrics Chicago, Illinois
Indiana University School of Medicine Stephan A. Kohlhoff, MD Emergency Medical Services for Children
Riley Children’s Hospital Assistant Professor of Pediatrics and Medicine
Indianapolis, Indiana Associate Director, Pediatric Infectious Diseases John F. Kuttesch Jr., MD, PhD
Coccidioidomycosis (Coccidioides species) SUNY Downstate Medical Center Chief, Division of Pediatric Hematology/Oncology
Brooklyn, New York Department of Pediatrics
Bruce L. Klein, MD Chlamydia (Chlamydophila) pneumoniae University of New Mexico School of Medicine
Visiting Associate Professor of Pediatrics Psittacosis (Chlamydia psittaci) Albuquerque, New Mexico
Johns Hopkins University School of Medicine Brain Tumors in Childhood
Associate Director, Pediatric Emergency Medicine Mark A. Kostic, MD
Director, Pediatric Transport Associate Professor of Pediatrics and Emergency Jennifer M. Kwon, MD, MPH
Johns Hopkins Children’s Center Medicine Associate Profess or of Pediatrics and Neurology
Baltimore, Maryland Division of Pediatric Emergency Medicine University of Rochester School of Medicine
Interfacility Transport of the Seriously Ill or Injured Medical College of Wisconsin Associate Director, Clinic for Inherited Metabolic
Pediatric Patient Associate Medical Director Diseases
Acute Care of the Victim of Multiple Trauma Wisconsin Poison Center Golisano Children’s Hospital
Milwaukee, Wisconsin Rochester, New York
Bruce S. Klein, MD Poisoning Neurodegenerative Disorders of Childhood
Professor of Pediatrics and Medical Microbiology
University of Wisconsin School of Medicine Linda E. Krach, MD Catherine S. Lachenauer, MD
Madison, Wisconsin Adjunct Professor Assistant Professor of Pediatrics
Blastomycosis (Blastomyces dermatitidis) Department of Physical Medicine and Harvard Medical School
Rehabilitation Division of Infectious Diseases
Michael D. Klein, MD, FACS, FAAP University of Minnesota School of Medicine Boston Children’s Hospital
Arvin I. Philippart MD Endowed Chair of President, Courage Kenny Rehabilitation Institute Boston, Massachusetts
Pediatric Surgical Research (part of Allina Health) Group B Streptococcus
Professor of Surgery Minneapolis, Minnesota
Wayne State University School of Medicine Severe Traumatic Brain Injury
Children’s Hospital of Michigan
Detroit, Michigan
Surgical Conditions of the Anus and Rectum
 Contributors xxi

Stephan Ladisch, MD Phillip S. LaRussa, MD Norma B. Lerner, MD, MPH

Professor of Pediatrics and Biochemistry/Molecular Professor of Pediatrics Special Advisor to the Director
Biology Columbia University Medical Center Division of Blood Diseases and Resources
Department of Pediatrics New York, New York National Heart, Lung, and Blood Institute
George Washington University School of Medicine Varicella-Zoster Virus Infections National Institutes of Health
Children’s Research Institute Bethesda, Maryland
Department of Hematology and Oncology J. Todd R. Lawrence, MD, PhD The Anemias
Children’s National Medical Center Assistant Professor Congenital Hypoplastic Anemia (Diamond-Blackfan
Washington, DC Department of Orthopaedic Surgery Anemia)
Histiocytosis Syndromes of Childhood University of Pennsylvania Perelman School of Pearson Syndrome
Medicine Acquired Pure Red Blood Cell Anemia
Stephen H. LaFranchi, MD Attending Orthopaedic Surgeon Anemia of Chronic Disease and Renal Disease
Professor of Pediatrics Children’s Hospital of Philadelphia Congenital Dyserythropoietic Anemias
Division of Pediatric Endocrinology Philadelphia, Pennsylvania Physiologic Anemia of Infancy
Oregon Health & Science University The Knee Megaloblastic Anemias
Portland, Oregon
Thyroid Development and Physiology Brendan Lee, MD, PhD Steven O. Lestrud, MD
Defects of Thyroxine-Binding Globulin Robert and Janice McNair Endowed Chair in Assistant Professor of Pediatrics
Hypothyroidism Molecular and Human Genetics Northwestern University Feinberg School of
Thyroiditis Professor, Department of Molecular and Human Medicine
Goiter Genetics Medical Director, Respiratory Care
Hyperthyroidism Baylor College of Medicine Ann & Robert H. Lurie Children’s Hospital of
Carcinoma of the Thyroid Houston, Texas Chicago
Integration of Genetics into Pediatric Practice Chicago, Illinois
Oren J. Lakser, MD The Genetic Approach in Pediatric Medicine Bronchopulmonary Dysplasia
Assistant Professor of Pediatrics The Human Genome
Northwestern University Feinberg School of Patterns of Genetic Transmission Donald Y.M. Leung, MD, PhD
Medicine Cytogenetics Edelstein Family Chair of Pediatric
Associate Clinician Specialist Genetics of Common Disorders Allergy-Immunology
Division of Pulmonary Medicine National Jewish Health
Ann & Robert H. Lurie Children’s Hospital of K. Jane Lee, MD, MA Professor of Pediatrics
Chicago Associate Professor University of Colorado School of Medicine
Chicago, Illinois Department of Pediatrics Denver, Colorado
Bronchiectasis Medical College of Wisconsin Atopic Dermatitis (Atopic Eczema)
Pulmonary Abscess Division of Pediatric Critical Care
Children’s Hospital of Wisconsin Chris A. Liacouras, MD
Marc B. Lande, MD, MPH Milwaukee, Wisconsin Professor of Pediatrics
Professor of Pediatrics Brain Death University of Pennsylvania Perelman School of
Division of Pediatric Nephrology Medicine
University of Rochester Medical Center J. Steven Leeder, PharmD, PhD Co-Director, Center for Pediatric Eosinophilic
School of Medicine and Dentistry Marion Merrell Dow / Missouri Endowed Chair in Disorders
Rochester, New York Pediatric Pharmacology The Children’s Hospital of Philadelphia
Systemic Hypertension Chief, Division of Pediatric Pharmacology and Philadelphia, Pennsylvania
Medical Toxicology Normal Digestive Tract Phenomena
Philip J. Landrigan, MD, MSc, FAAP Children’s Mercy Hospitals and Clinics Major Symptoms and Signs of Digestive Tract
Dean for Global Health Kansas City, Missouri; Disorders
Ethel H. Wise Professor and Chair, Department of Adjunct Professor Normal Development, Structure, and Function
Preventive Medicine Department of Pharmacology, Toxicology, and (Stomach)
Director, Children’s Environmental Health Center Therapeutics Pyloric Stenosis and Other Congenital Anomalies of
Icahn School of Medicine at Mount Sinai Kansas University School of Medicine the Stomach
New York, New York Kansas City, Kansas Intestinal Atresia, Stenosis, and Malrotation
Chemical Pollutants Pediatric Pharmacogenetics, Pharmacogenomics, Intestinal Duplications, Meckel Diverticulum, and
and Pharmacoproteomics Other Remnants of the Omphalomesenteric Duct
Gregory L. Landry, MD Motility Disorders and Hirschsprung Disease
Professor Rebecca K. Lehman, MD Ileus, Adhesions, Intussusception, and Closed-Loop
Department of Pediatrics Assistant Professor of Pediatrics Obstructions
University of Wisconsin—Madison Division of Pediatric Neurology Foreign Bodies and Bezoars
School of Medicine and Public Health Medical University of South Carolina Functional Abdominal Pain (Nonorganic Chronic
Madison, Wisconsin Charleston, South Carolina Abdominal Pain)
Epidemiology and Prevention of Injuries Neurologic Evaluation Malformations
Heat Injuries Chorea, Athetosis, Tremor Ascites
Female Athletes: Menstrual Problems and the Risk Peritonitis
of Osteopenia Michael J. Lentze, MD
Performance-Enhancing Aids Professor of Pediatrics Christopher W. Liebig, MD
Division of Pediatric Gastroenterology Pediatric Sports Medicine Fellow
Wendy G. Lane, MD, MPH, FAAP Medizinische Universität Bonn Akron Children’s Hospital
Assistant Professor Bonn, Germany Akron, Ohio
Departments of Pediatrics and Epidemiology and Evaluation of Children with Suspected Intestinal Sports-Related Traumatic Brain Injury (Concussion)
Preventive Medicine Malabsorption
University of Maryland School of Medicine Enzyme Deficiencies
Baltimore, Maryland
Abused and Neglected Children
xxii Contributors

Timothy P. Lindquist, MD Anna Lena Lopez, MD, MPH Joseph A. Majzoub, MD

Pediatric Ophthalmologist Research Associate Professor Thomas Morgan Rotch Professor of Pediatrics
Children’s Mercy Hospital Institute of Child Health and Human Development Professor of Medicine
Kansas City, Missouri University of the Philippines Manila—National Harvard Medical School
Growth and Development (Eye) Institutes of Health Chief, Division of Endocrinology
Examination of the Eye Clinical Associate Professor, Department of Boston Children’s Hospital
Abnormalities of Refraction and Accommodation Pediatrics Boston, Massachusetts
Disorders of Vision University of the Philippines College of Medicine Diabetes Insipidus
Abnormalities of Pupil and Iris Manila, Philippines Other Abnormalities of Arginine Vasopressin
Disorders of Eye Movement and Alignment Cholera Metabolism and Action
Abnormalities of the Lids
Disorders of the Lacrimal System Steven V. Lossef, MD Asim Maqbool, MD
Disorders of the Conjunctiva Head, Pediatric Interventional Radiology Assistant Professor of Pediatrics
Abnormalities of the Cornea Division of Diagnostic Imaging and Radiology University of Pennsylvania Perelman School of
Abnormalities of the Lens Children’s National Medical Center Medicine
Disorders of the Uveal Tract Washington, DC Division of Gastroenterology, Hepatology, and
Disorders of the Retina and Vitreous Pertussis (Bordetella pertussis and Bordetella Nutrition
Abnormalities of the Optic Nerve parapertussis) Children’s Hospital of Philadelphia
Childhood Glaucoma Pleurisy, Pleural Effusions, and Empyema Philadelphia, Pennsylvania
Orbital Abnormalities Pneumothorax Nutritional Requirements
Orbital Infections Hemothorax
Injuries to the Eye Chlyothorax Ashley M. Maranich, MD
Pediatric Infectious Disease
Andrew H. Liu, MD Jennifer A. Lowry, MD Director, Transitional Year Program
Professor Associate Professor of Pediatrics San Antonio Military Medical Center
Department of Pediatrics University of Missouri—Kansas City School of Fort Sam Houston, Texas
National Jewish Health Medicine Malassezia
University of Colorado School of Medicine Section Chief, Medical Toxicology
Denver, Colorado Division of Clinical Pharmacology and Therapeutic Mona Marin, MD
Childhood Asthma Innovations Medical Epidemiologist
Medical Director, Center for Environmental Health Epidemiology Branch, Division of Viral Diseases
Stanley F. Lo, PhD Children’s Mercy Hospitals and Clinics National Center for Immunization and Respiratory
Associate Professor of Pathology Kansas City, Missouri Diseases
Medical College of Wisconsin Principles of Drug Therapy Centers for Disease Control and Prevention
Co-Director, Clinical Laboratories Atlanta, Georgia
Co-Director, Biochemical Genetics Laboratory Nora T. MacZura, MD Varicella-Zoster Virus Infections
Technical Director, Chemistry and Point of Care Division of Gynecologic Oncology
Testing Laboratories Department of Obstetrics and Gynecology Joan C. Marini, MD, PhD
Children’s Hospital of Wisconsin Springfield Clinic Chief, Bone and Extracellular Matrix Branch
Milwaukee, Wisconsin Springfield, Illinois National Institute for Child Health and
Laboratory Testing in Infants and Children Neoplasms and Adolescent Screening for Human Development
Reference Intervals for Laboratory Tests and Papillomavirus National Institutes of Health
Procedures Bethesda, Maryland
Prashant V. Mahajan, MD, MPH, MBA Osteogenesis Imperfecta
Franco Locatelli, MD Professor of Pediatrics and Emergency Medicine
Professor of Pediatrics Carman and Ann Adams Department of Pediatrics Thomas C. Markello, MD, PhD
University of Pavia Wayne State University School of Medicine National Human Genome Research Institute
Pavia, Italy; Division Chief and Research Director National Institutes of Health
Director, Department of Pediatric Hematology and Director, Center for Quality and Innovation Bethesda, Maryland
Oncology Pediatric Emergency Medicine Genetic Approaches to Rare and Undiagnosed
IRCCS Ospedale Pediatrico Bambino Gesù Children’s Hospital of Michigan Diseases
Rome, Italy Detroit, Michigan
Principles and Clinical Indications of Hematopoietic Heavy Metal Intoxication Morri Markowitz, MD
Stem Cell Transplantation Professor of Pediatrics and Medicine
Hematopoietic Stem Cell Transplantation from Akhil Maheshwari, MD Albert Einstein College of Medicine
Alternative Sources and Donors Associate Professor of Pediatrics and Clinical Director, Pediatric Environmental Sciences
Graft-Versus-Host Disease, Rejection, and Pharmacology The Children’s Hospital at Montefiore
Venoocclusive Disease University of Illinois, Chicago Bronx, New York
Infectious Complications of Hematopoietic Stem Cell Chief, Division of Neonatology Lead Poisoning
Transplantation Director, Center for Neonatal and Pediatric
Late Effects of Hematopoietic Stem Cell Gastrointestinal Disease Kevin P. Marks, MD
Transplantation Medical Director, Neonatal Intensive Care Unit Clinical Assistant Professor
and Intermediate Care Nursery Department of Pediatrics
John H. Lockhart, MD Children’s Hospital of University of Illinois Oregon Health & Science University School of
Clinical Assistant Professor Chicago, Illinois Medicine
Departments of Orthopedics and Sports Medicine Diaphragmatic Hernia General Pediatrician
Seattle Children’s Hospital Foramen of Morgagni Hernia PeaceHealth Medical Group
Seattle, Washington Paraesophageal Hernia Portland, Oregon
Cervical Spinal Injuries Eventration Developmental-Behavioral Screening and
Digestive System Disorders Surveillance
Sarah S. Long, MD Blood Disorders
Professor of Pediatrics
Drexel University College of Medicine
Chief, Section of Infectious Diseases
St. Christopher’s Hospital for Children
Philadelphia, Pennsylvania
Pertussis (Bordetella pertussis and Bordetella
parapertussis)
 Contributors xxiii

Stacene R. Maroushek, MD, PhD, Dennis J. Matthews, MD Mary A. McMahon, MD

MPH Professor and Chair Assistant Professor
Assistant Professor of Pediatrics Department of Physical Medicine and Department of Pediatrics
Division of Pediatric Infectious Diseases and Rehabilitation University of Cincinnati College of Medicine
Immunology University of Colorado School of Medicine Director, Division of Physical Medicine and
University of Minnesota Medical School Medical Director Rehabilitation
Pediatric Infectious Diseases and General Children’s Hospital Rehabilitation Center Director, Physical Medicine and Rehabilitation
Pediatrics PPAARDI-in-Chief Residency Program
Hennepin County Medical Center Children’s Hospital Colorado Cincinnati Children’s Hospital Medical Center
Minneapolis, Minnesota Denver, Colorado Cincinnati, Ohio
Medical Evaluation of Immigrant (Foreign-Born) Principles of Rehabilitation Medicine Spinal Cord Injury and Spinal Cord Autonomic
Children for Infectious Diseases Crisis Management
Principles of Antimycobacterial Therapy Robert L. Mazor, MD
Clinical Associate Professor Asuncion Mejias, MD, PhD, MSCS
Kari L. Martin, MD Department of Pediatrics Assistant Professor of Pediatrics
Assistant Professor of Dermatology and Child University of Washington School of Medicine Section of Infectious Diseases and Immunology
Health Division of Critical Care and Cardiac Surgery The Ohio State University College of Medicine
Associate Residency Program Director Department Clinical Director, CICU The Research Institute at Nationwide Children’s
of Dermatology Seattle Children’s Hospital and Regional Medical Hospital
University of Missouri School of Medicine Center Columbus, Ohio
Columbia, Missouri Seattle, Washington Hansen Disease (Mycobacterium leprae)
Diseases of the Neonate Pulmonary Edema Mycoplasma pneumoniae
Cutaneous Defects Genital Mycoplasmas (Mycoplasma hominis,
Ectodermal Dysplasias Megan E. McCabe, MD Mycoplasma genitalium, and Ureaplasma
Vascular Disorders Assistant Professor urealyticum)
Cutaneous Nevi Department of Pediatrics
Disorders of Keratinization Yale School of Medicine Peter C. Melby, MD
Disorders of the Sweat Glands New Haven, Connecticut Professor of Internal Medicine (Infectious
Disorders of Hair Loss, Separation, and Bereavement Diseases), Microbiology and Immunology, and
Disorders of the Nails Pathology
Tumors of the Skin Susanna A. McColley, MD Director, Center for Tropical Diseases
Professor of Pediatrics University of Texas Medical Branch at Galveston
Wilbert H. Mason Jr., MD, MPH Northwestern University Feinberg School of Galveston, Texas
Professor Emeritus of Clinical Pediatrics Medicine Leishmaniasis (Leishmania)
University of Southern California Keck School of Director, Clinical and Translational Research
Medicine Stanley Manne Children’s Research Institute Alexandra N. Menchise, MD
Chief, Pediatric Infectious Diseases Ann & Robert H. Lurie Children’s Hospital of Pediatric Gastroenterology Fellow
Children’s Hospital of Los Angeles Chicago Cincinnati Children’s Hospital Medical Center
Los Angeles, California Chicago, Illinois Cincinnati, Ohio
Measles Pulmonary Tumors Metabolic Diseases of the Liver
Rubella Extrapulmonary Diseases with Pulmonary
Mumps Manifestations Diane F. Merritt, MD
Professor
Christopher Mastropietro, MD Margaret M. McGovern, MD, PhD Department of Obstetrics and Gynecology
Assistant Professor Professor and Chair Director, Pediatric and Adolescent Gynecology
Department of Pediatrics Department of Pediatrics Washington University School of Medicine in St.
Wayne State University School of Medicine Stony Brook University School of Medicine Louis
Associate Fellowship Director Physician-in-Chief, Stony Brook Long Island St. Louis, Missouri
Division of Critical Care Children’s Hospital History and Physical Examination (Gynecology)
Children’s Hospital of Michigan Stony Brook, New York Vulvovaginitis
Detroit, Michigan Lipidoses (Lysosomal Storage Disorders) Bleeding
Mechanical Ventilation Mucolipidoses Breast Concerns
Disorders of Glycoprotein Degradation and Neoplasms and Adolescent Screening for Human
Kimberlee M. Matalon, PhD Structure Papillomavirus
Associate Professor
Department of Health and Human Performance Heather S. McLean, MD Ethan A. Mezoff, MD
University of Houston Associate Professor of Pediatrics Pediatric Gastroenterology Fellow
Houston, Texas Duke University School of Medicine Cincinnati Children’s Hospital Medical Center
Aspartic Acid (Canavan Disease) Medical Director Cincinnati, Ohio
Pediatric Hospital Medicine Clostridium difficile Infection
Reuben K. Matalon, MD, PhD Duke Children’s Hospital
Professor Durham, North Carolina Marian G. Michaels, MD, MPH
Department of Pediatrics and Genetics Failure to Thrive Professor of Pediatrics and Surgery
University of Texas Medical Branch University of Pittsburgh School of Medicine
University of Texas Children’s Hospital Rima McLeod, MD Division of Pediatric Infectious Diseases
Galveston, Texas Jules and Doris Stein Research to Prevent Children’s Hospital of Pittsburgh of UPMC
Aspartic Acid (Canavan Disease) Blindness Professor of Ophthalmology Pittsburgh, Pennsylvania
Departments of Ophthalmology and Visual Infections in Immunocompromised Persons
Roshni Mathew, MD Sciences and Pediatrics
Clinical Instructor in Pediatrics Medical Director, Toxoplasmosis Center Mohamad A. Mikati, MD
Division of Pediatric Infectious Diseases University of Chicago School of Medicine Wilburt C. Davison Professor of Pediatrics and
Stanford University School of Medicine Chicago, Illinois Professor of Neurobiology
Stanford, California Toxoplasmosis (Toxoplasma gondii) Chief, Division of Pediatric Neurology
Central Nervous System Infections Duke University Medical Center
Brain Abscess Durham, North Carolina
Seizures in Childhood
Conditions That Mimic Seizures
xxiv Contributors

Henry Milgrom, MD Beth Moughan, MD Jayne M. Ness, MD, PhD

Professor of Pediatrics Professor of Clinical Pediatrics Associate Professor of Pediatrics
National Jewish Health Assistant Dean, Affiliate Faculty Development Division of Pediatric Neurology
University of Colorado School of Medicine Associate Chair, Clinical Affairs University of Alabama, Birmingham
Denver, Colorado Section Chief, Ambulatory Pediatrics Birmingham, Alabama
Allergic Rhinitis Temple University School of Medicine Demyelinating Disorders of the Central Nervous
Philadelphia, Pennsylvania System
E. Kathryn Miller, MD, MPH Sporotrichosis (Sporothrix schenckii)
Assistant Professor Kathleen A. Neville, MD, MS
Departments of Pediatrics and Allergy and James R. Murphy, PhD Associate Professor of Pediatrics
Immunology Professor of Pediatrics University of Missouri—Kansas City School of
Vanderbilt University School of Medicine Director, Pediatric Infectious Disease Research Medicine
Nashville, Tennessee University of Texas Health Science Center Director, Experimental Therapeutics in Pediatric
The Common Cold Houston, Texas Cancer
Rhinoviruses Campylobacter Department of Pediatric Hematology/Oncology
Yersinia Children’s Mercy Hospitals and Clinics
Jonathan W. Mink, MD, PhD Kansas City, Missouri
Frederick A. Horner MD Endowed Professor in Kevin P. Murphy, MD Pediatric Pharmacogenetics, Pharmacogenomics,
Pediatric Neurology Medical Director Pediatric Rehabilitation and Pharmacoproteomics
Professor of Neurology, Neurobiology and Sanford Health Systems
Anatomy, Brain and Cognitive Sciences, and Bismarck, North Dakota; Mary A. Nevin, MD
Pediatrics Medical Director, Gillette Children’s Specialty Associate Professor of Pediatrics
Chief, Division of Child Neurology Healthcare Northwestern University Feinberg School of
Vice-Chair, Department of Neurology Duluth Clinic Medicine
University of Rochester Medical Center Duluth, Minnesota Department of Pulmonary and Critical Care
Rochester, New York Management of Musculoskeletal Injury Medicine
Movement Disorders Specific Sports and Associated Injuries Ann & Robert H. Lurie Children’s Hospital of
Chicago
R. Justin Mistovich, MD Timothy F. Murphy, MD Chicago, Illinois
Clinical Fellow Distinguished Professor Pulmonary Hemosiderosis
Division of Pediatric Orthopaedic Surgery Director, UB Clinical and Translational Research Pulmonary Embolism, Infarction, and Hemorrhage
University of Pennsylvania Perelman School of Center
Medicine University at Buffalo, State University of New York Jane W. Newburger, MD
Children’s Hospital of Philadelphia School of Medicine and Biomedical Sciences Commonwealth Professor of Pediatrics
Philadelphia, Pennsylvania Buffalo, New York Harvard Medical School
The Spine Moraxella catarrhalis Associate Cardiologist-in-Chief, Research and
Education
Grant A. Mitchell, MD Thomas S. Murray, MD, PhD Director, Cardiac Neurodevelopmental Program
Professor of Pediatrics Associate Professor of Medical Sciences Director, Kawasaki Program
Division of Medical Genetics Quinnipiac University Frank H Netter MD School Children’s Hospital Boston
University of Montreal Faculty of Medicine of Medicine Boston, Massachusetts
Service de Genetique Medicale Hamden, Connecticut Kawasaki Disease
Hospital Ste-Justine Listeria monocytogenes
Montreal, Quebec, Canada Pseudomonas, Burkholderia, and Peter E. Newburger, MD
Tyrosine Stenotrophomonas Ali and John Pierce Professor of Pediatric
Hematology/Oncology
Esi Morgan-DeWitt, MD, MSCE René P. Myers, MD Vice-Chair for Research
Associate Professor of Pediatrics Chief Resident Department of Pediatrics
University of Cincinnati College of Medicine Department of Plastic Surgery University of Massachusetts Medical School
Division of Rheumatology University of Rochester Medical Center Worcester, Massachusetts
James M. Anderson Center for Health Systems Rochester, New York Leukopenia
Excellence Deformational Plagiocephaly Leukocytosis
Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio Mindo J. Natale, PsyD Linda S. Nield, MD
Treatment of Rheumatic Diseases Assistant Professor of Psychology Professor of Pediatrics
Sarcoidosis University of South Carolina School of Medicine Director, Pediatrics Residency Program
Senior Staff Psychologist West Virginia University School of Medicine
Anna-Barbara Moscicki, MD GHS Children’s Hospital Morgantown, West Virginia
Professor of Pediatrics Greenville, South Carolina Fever
University of California, San Francisco Neurodevelopmental Function and Dysfunction in Fever Without a Focus
Senior Director, Pediatric Glaser Clinic the School-Age Child
San Francisco, California Susan Niermeyer, MD, MPH, FAAP
Human Papillomaviruses William A. Neal, MD Professor of Pediatrics
Professor of Pediatrics Section of Neonatology
Lovern R. Moseley, PhD Division of Pediatric Cardiology University of Colorado School of Medicine
Department of Psychiatry West Virginia University School of Medicine Aurora, Colorado
Boston Medical Center Morgantown, West Virginia Altitude-Associated Illness in Children (Acute
Boston, Massachusetts Disorders of Lipoprotein Metabolism and Transport Mountain Sickness)
Mood Disorders
Disruptive, Impulse-Control, and Conduct Disorders Maureen R. Nelson, MD
Pediatric Subspecialty Services
Dell’s Children’s Medical Center of Central Texas
Austin, Texas
Birth Brachial Plexus Palsy

Zehava L. Noah, MD Jean-Marie Okwo-Bele, MD, MPH
Associate Professor of Pediatrics Director
Northwestern University Feinberg School of Immunization, Vaccines, and Biologicals
Medicine Department
Division of Pediatric Critical Care Medicine World Health Organization
Ann & Robert H. Lurie Children’s Hospital of Geneva, Switzerland
Chicago International Immunization Practices
Chicago, Illinois
Chronic Severe Respiratory Insufficiency Keith T. Oldham, MD
Professor and Chief
Lawrence M. Nogee, MD Division of Pediatric Surgery
Professor of Pediatrics Medical College of Wisconsin
Department of Pediatrics Children’s Hospital of Wisconsin
Division of Neonatology and Perinatology Milwaukee, Wisconsin
Johns Hopkins University School of Medicine Acute Appendicitis
Baltimore, Maryland Inguinal Hernias
Diffuse Lung Diseases in Childhood Epigastric Hernia
Robert L. Norris, MD, FACEP, FAAEM Joyce L. Oleszek, MD
Professor of Surgery Associate Professor
Chief, Division of Emergency Medicine Department of Physical Medicine and
Stanford University Medical Center Rehabilitation
Stanford, California University of Colorado School of Medicine
Envenomations Attending Physician
Children’s Hospital Colorado
Anna Nowak-Wȩgrzyn, MD Denver, Colorado
Associate Professor of Pediatrics Spasticity
Jaffe Food Allergy Institute
Icahn School of Medicine at Mount Sinai Scott E. Olitsky, MD
New York, New York Professor of Ophthalmology
Serum Sickness University of Kansas School of Medicine
Food Allergy and Adverse Reactions to Foods University of Missouri—Kansas City School of
Medicine
Stephen K. Obaro, MD, PhD, FRCPCH Section Chief, Ophthalmology
Professor of Pediatrics Children’s Mercy Hospitals and Clinics
Division of Infectious Diseases Kansas City, Missouri
University of Nebraska Medical Center Growth and Development (Eye)
Omaha, Nebraska Examination of the Eye
Nonvenereal Treponemal Infections Abnormalities of Refraction and Accommodation
Relapsing Fever (Borrelia) Disorders of Vision
Abnormalities of Pupil and Iris
Makram M. Obeid, MD Disorders of Eye Movement and Alignment
Clinical Fellow in Neurology Abnormalities of the Lids
Boston Children’s Hospital Disorders of the Lacrimal System
Boston, Massachusetts Disorders of the Conjunctiva
Conditions That Mimic Seizures Abnormalities of the Cornea
Abnormalities of the Lens
Hope L. O’Brien, MD Disorders of the Uveal Tract
Assistant Professor of Pediatrics and Neurology Disorders of the Retina and Vitreous
University of Cincinnati College of Medicine Abnormalities of the Optic Nerve
Director, Young Adult Headache Program Childhood Glaucoma
Division of Neurology Orbital Abnormalities
Cincinnati Children’s Hospital Medical Center Orbital Infections
Cincinnati, Ohio Injuries to the Eye
Headaches
John M. Olsson, MD, CPE
Theresa J. Ochoa, MD Professor of Pediatrics
Associate Professor of Epidemiology and Pediatrics Division Chief, General Pediatrics
The University of Texas Health Science Center at Brody School of Medicine
Houston East Carolina University
Houston, Texas; Greenville, North Carolina
Universidad Peruana Cayetano Heredia The Newborn
Lima, Peru
Shigella Amanda K. Ombrello, MD
Escherichia coli Staff Clinician
National Human Genome Research Institute
Robin K. Ohls, MD National Institutes of Health
Professor of Pediatrics Bethesda, Maryland
University of New Mexico School of Medicine Hereditary Periodic Fever Syndromes and Other
Albuquerque, New Mexico Systemic Autoinflammatory Diseases
Development of the Hematopoietic System Amyloidosis
Contributors xxv
Susan R. Orenstein, MD
Professor Emerita
University of Pittsburgh School of Medicine
Division of Pediatric Gastroenterology
Children’s Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania
Embryology, Anatomy, and Function of the
Esophagus
Congenital Anomalies: Esophageal Atresia and
Tracheoesophageal Fistula
Obstructing and Motility Disorders of the Esophagus
Dysmotility
Hiatal Hernia
Gastroesophageal Reflux Disease
Eosinophilic Esophagitis and Non–Gastroesophageal
Reflux Disease Esophagitis
Esophageal Perforation
Esophageal Varices
Ingestions
Walter A. Orenstein, MD, DSc (Hon)
Professor of Medicine and Pediatrics
Associate Director, Emory Vaccine Center
Emory University
Atlanta, Georgia
Immunization Practices
Marisa Osorio, DO
Acting Assistant Professor
Department of Rehabilitation Medicine
University of Washington School of Medicine
Seattle Children’s Hospital
Seattle, Washington
Ambulation Assistance
Patrick O’Toole, MD
Clinical Fellow
Division of Pediatric Orthopaedic Surgery
University of Pennsylvania Perelman School of
Medicine
Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania
The Neck
Judith A. Owens, MD, MPH
Associate Professor
Harvard Medical School
Director of Sleep Medicine
Boston Children’s Hospital
Boston, Massachusetts
Sleep Medicine
Seza Özen, MD
Professor of Paediatrics
Division of Paediatric Rheumatology
Hacettepe University
Ankara, Turkey
Behçet Disease
Charles H. Packman, MD
Professor of Medicine
University of North Carolina School of Medicine
Levine Cancer Institute, Hematologic Oncology
and Blood Disorders
Charlotte, North Carolina
Hemolytic Anemias Resulting from Extracellular
Factors—Immune Hemolytic Anemias
xxvi Contributors

Priya Pais, MBBS, MS Timothy R. Peters, MD Craig C. Porter, MD

Assistant Professor of Pediatrics
Division of Nephrology
Medical College of Wisconsin
Wauwatosa, Wisconsin
Lower Urinary Tract Causes of Hematuria
Introduction to the Child with Proteinuria
Fixed Proteinuria
Nephrotic Syndrome
Cortical Necrosis
Tonya M. Palermo, PhD
Professor
Department of Anesthesiology
University of Washington School of Medicine
Seattle Children’s Hospital Research Institute
Seattle, Washington
Pediatric Pain Management
Cynthia G. Pan, MD
Professor of Pediatrics
Section Head, Pediatric Nephrology
Medical College of Wisconsin
Medical Director, Pediatric Dialysis and Transplant
Services
Children’s Hospital of Wisconsin
Milwaukee, Wisconsin
Introduction to Glomerular Diseases
Clinical Evaluation of the Child with Hematuria
Isolated Glomerular Diseases with Recurrent Gross
Hematuria
Glomerulonephritis Associated with Infections
Glomerulonephritis Associated with Systemic Lupus
Erythematosus
Diane E. Pappas, MD, JD
Professor
Department of Pediatrics
University of Virginia School of Medicine
Charlottesville, Virginia
Sinusitis
Retropharyngeal Abscess, Lateral Pharyngeal
(Parapharyngeal) Abscess, and Peritonsillar
Cellulitis/Abscess
Elizabeth P. Parks, MD, MSCE
Assistant Professor of Pediatrics
Division of Gastroenterology, Hepatology, and
Nutrition
University of Pennsylvania Perelman School of
Medicine
Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania
Nutritional Requirements
Feeding Healthy Infants, Children, and Adolescents
John S. Parks, MD, PhD
Professor of Pediatrics
Division of Pediatric Endocrinology
Emory University School of Medicine
Atlanta, Georgia
Hormones of the Hypothalamus and Pituitary
Hypopituitarism
Maria Jevitz Patterson, MD, PhD
Professor Emeritus of Microbiology and Molecular
Genetics
Michigan State University College of Human
Medicine
East Lansing, Michigan
Syphilis (Treponema pallidum)
Associate Professor of Pediatrics Professor and Vice-Chair for Faculty
Section of Pediatric Infectious Diseases Department of Pediatrics
Wake Forest University School of Medicine Division of Nephrology
Winston-Salem, North Carolina Medical College of Wisconsin
Streptococcus pneumoniae (Pneumococcus) Milwaukee, Wisconsin
Upper Urinary Tract Causes of Hematuria
Larry K. Pickering, MD Hematologic Diseases Causing Hematuria
Senior Advisor to the Director Anatomic Abnormalities Associated with Hematuria
National Center for Immunization and Respiratory Transient Proteinuria
Diseases Orthostatic (Postural) Proteinuria
Executive Secretary Tubulointerstitial Nephritis
Advisory Committee for Immunization Practices Toxic Nephropathy
Centers for Disease Control and Prevention
Adjunct Professor of Pediatrics Diego Preciado, MD, PhD
Emory University School of Medicine Joseph E. Robert Jr. Professor of Otolaryngology
Atlanta, Georgia Children’s National Medical Center
Immunization Practices Associate Professor of Pediatrics and Surgery
George Washington University School of Medicine
Misha L. Pless, MD Washington, DC
Associate Professor of Neurology Otitis Media
Harvard Medical School
Chief, Division of Neuro-ophthalmology David T. Price, MD
Chief, Division of General Neurology Clinical Professor
Director, Neurology Urgent Access Center Department of Pediatrics
Massachusetts General Hospital East Carolina University
Boston, Massachusetts Greenville, North Carolina
Idiopathic Intracranial Hypertension/Pseudotumor Failure to Thrive
Cerebri
Charles G. Prober, MD
Laura S. Plummer, MD Professor of Pediatrics, Microbiology, and
Assistant Professor Immunology
Department of Ophthalmology Senior Associate Dean, Medical Education
University of Missouri—Kansas City School of Stanford University School of Medicine
Medicine Stanford, California
Children’s Mercy Hospital Central Nervous System Infections
Kansas City, Missouri Brain Abscess
Growth and Development (Eye)
Examination of the Eye David W. Pruitt, MD
Abnormalities of Refraction and Accommodation Assistant Professor
Disorders of Vision Department of Pediatrics
Abnormalities of Pupil and Iris University of Cincinnati College of Medicine
Disorders of Eye Movement and Alignment Medical Director, Inpatient Pediatric Rehabilitation
Abnormalities of the Lids Unit
Disorders of the Lacrimal System Director, Pediatric Rehabilitation Medicine
Disorders of the Conjunctiva Fellowship
Abnormalities of the Cornea Cincinnati Children’s Hospital Medical Center
Abnormalities of the Lens Cincinnati, Ohio
Disorders of the Uveal Tract Spinal Cord Injury and Spinal Cord Autonomic
Disorders of the Retina and Vitreous Crisis Management
Abnormalities of the Optic Nerve
Childhood Glaucoma Linda Quan, MD
Orbital Abnormalities Professor
Orbital Infections Department of Pediatrics
Injuries to the Eye University of Washington School of Medicine
Attending Physician
Andrew J. Pollard, MBBS, BSc, Division of Emergency Medicine
FRCP(UK), FRCPCH, PhD Seattle Children’s Hospital
Professor of Paediatric Infection and Immunity Seattle, Washington
Department of Paediatrics Drowning and Submersion Injury
Director of the Oxford Vaccine Group
University of Oxford Elisabeth H. Quint, MD
Honorary Consultant Paediatrician Professor of Obstetrics and Gynecology
Children’s Hospital Director, Fellowship in Pediatric and Adolescent
Oxford, United Kingdom Gynecology
Neisseria meningitidis (Meningococcus) Van Voightlander Women’s Hospital
University of Michigan Medical School
Ann Arbor, Michigan
Gynecologic Care for Girls with Special Needs

C. Egla Rabinovich, MD, MPH Harold L. Rekate, MD, FACS, FAAP
Associate Professor of Pediatrics Professor of Neurosurgery
Duke University School of Medicine Hofstra Northshore School of Medicine
Co-Chief, Division of Pediatric Rheumatology Director, The Chiari Institute
Duke University Health System Harvey Cushing Neurosciences Institute
Durham, North Carolina Great Neck, New York
Evaluation of Suspected Rheumatic Disease Spinal Cord Disorders
Treatment of Rheumatic Diseases
Juvenile Idiopathic Arthritis Megan E. Reller, MD, PhD, MPH
Scleroderma and Raynaud Phenomenon Assistant Professor of Pathology, Medicine, and
Sjögren Syndrome International Health
Miscellaneous Conditions Associated with Arthritis Johns Hopkins University School of Medicine
Baltimore, Maryland
Leslie J. Raffini, MD Spotted Fever Group Rickettsioses
Associate Professor of Pediatrics Scrub Typhus (Orientia tsutsugamushi)
University of Pennsylvania Perelman School of Typhus Group Rickettsioses
Medicine Ehrlichioses and Anaplasmosis
Division of Hematology Q Fever (Coxiella burnetii)
Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania Jorges D. Reyes, MD
Hemostasis Assistant Professor of Surgery
Hereditary Predisposition to Thrombosis Division of Transplantation
Thrombotic Disorders in Children University of Washington School of Medicine
Disseminated Intravascular Coagulation Chief, Division of Transplant Surgery
Seattle Children’s Hospital
Octavio Ramilo, MD Seattle, Washington
Henry G. Cramblett Chair in Medicine Intestinal Transplantation in Children with
Professor of Pediatrics Intestinal Failure
The Ohio State University College of Medicine Liver Transplantation
Chief, Section of Infectious Diseases and
Immunology Geoffrey A. Rezvani, MD
Nationwide Children’s Hospital Assistant Professor
Columbus, Ohio Department of Pediatrics
Mycoplasma pneumoniae Drexel University College of Medicine
Section of Endocrinology, Diabetes, and
Denia Ramirez-Montealegre, MD Metabolism
Assistant Professor of Neurology St. Christopher’s Hospital for Children
University of Virginia School of Medicine Philadelphia, Pennsylvania;
Division of Pediatric Neurology Novo Nordisk, Inc.
UVA Children’s Hospital Princeton, New Jersey
Charlottesville, Virginia An Approach to Inborn Errors of Metabolism
Ataxias
Iraj Rezvani, MD
Asma Rashid, MD, MPH Professor of Pediatrics (Emeritus)
Department of Psychiatry Temple University School of Medicine
Boston Medical Center Adjunct Professor
Boston, Massachusetts Department of Pediatrics
Disruptive, Impulse-Control, and Conduct Disorders Drexel University College of Medicine
Section of Endocrinology, Diabetes, and
Giuseppe J. Raviola, MD Metabolism
Assistant Professor of Psychiatry and Global St. Christopher’s Hospital for Children
Health and Social Medicine Philadelphia, Pennsylvania
Harvard Medical School An Approach to Inborn Errors of Metabolism
Director, Psychiatry Quality Program Defects in Metabolism of Amino Acids
Boston Children’s Hospital
Boston, Massachusetts A. Kim Ritchey, MD
Autism Spectrum Disorder Professor of Pediatrics
Childhood Psychoses Vice-Chair for Clinical Affairs
Department of Pediatrics
Gerald V. Raymond, MD University of Pittsburgh School of Medicine
Professor of Neurology Division of Hematology/Oncology
University of Minnesota School of Medicine Children’s Hospital of Pittsburgh of UPMC
Chief of Pediatric Neurology Pittsburgh, Pennsylvania
University of Minnesota Medical Center, Fairview Principles of Diagnosis (Cancer)
Minneapolis, Minnesota Principles of Treatment
Disorders of Very Long Chain Fatty Acids The Leukemias
Ann M. Reed, MD Frederick P. Rivara, MD, MPH
Professor of Pediatrics Seattle Children’s Guild Endowed Chair in
Chair, Department of Pediatrics Pediatrics
Physician-in-Chief, Duke Children’s Professor and Vice-Chair, Department of Pediatrics
Duke University University of Washington School of Medicine
Durham, North Carolina Seattle, Washington
Juvenile Dermatomyositis Injury Control
Contributors xxvii
Elizabeth V. Robilotti, MD, MPH
Associate Director, Infection Control
Memorial Hospital Division of Infectious Diseases
Memorial Sloan Kettering Cancer Center
New York, New York
Legionella
Angela Byun Robinson, MD, MPH
Assistant Professor
Department of Pediatrics
Case Western Reserve University School of
Medicine
Program Director, Pediatric Rheumatology
University Hospitals Case Medical Center
Cleveland, Ohio
Juvenile Dermatomyositis
Miscellaneous Conditions Associated with Arthritis
Genie E. Roosevelt, MD, MPH
Associate Professor of Pediatrics
Department of Emergency Medicine
University of Colorado School of Medicine
Denver Health Medical Center
Denver, Colorado
Acute Inflammatory Upper Airway Obstruction
(Croup, Epiglottitis, Laryngitis, and Bacterial
Tracheitis)
David R. Rosenberg, MD
Professor and Chair, Department of Psychiatry
Miriam L. Hamburger Endowed Chair of Child
Psychiatry
Psychiatrist-in-Chief
Wayne State University and the Detroit Medical
Center
Detroit, Michigan
Anxiety Disorders
David S. Rosenblatt, MD
Holder, Dodd Q. Chu and Family Chair in Medical
Genetics
Professor, Departments of Human Genetics,
Medicine, Pediatrics, and Biology
Faculties of Medicine and Science
McGill University
Montreal, Quebec, Canada
Methionine
Valine, Leucine, Isoleucine, and Related Organic
Acidemias
Cindy Ganis Roskind, MD
Assistant Clinical Professor
Division of Pediatric Emergency Medicine
Columbia University College of Physicians and
Surgeons
New York, New York
Acute Care of the Victim of Multiple Trauma
A. Catharine Ross, PhD
Professor and Dorothy Foehr Huck Chair
Department of Nutritional Sciences
The Pennsylvania State University
University Park, Pennsylvania
Vitamin A Deficiencies and Excess
Mary M. Rotar, RN, BSN, CIC
Infection Prevention and Control Coordinator
Children’s Hospital of Wisconsin
Milwaukee, Wisconsin
Infection Prevention and Control
xxviii Contributors
Ranna A. Rozenfeld, MD Robert A. Salata, MD
Associate Professor of Pediatrics and Medical Professor and Executive Vice-Chair, Department of
Education Medicine
Northwestern University Feinberg School of Case Western Reserve University School of
Medicine Medicine
Division of Pediatric Critical Care Medicine Chief, Division of Infectious Diseases and HIV
Ann & Robert H. Lurie Children’s Hospital of Medicine
Chicago University Hospitals Case Medical Center
Chicago, Illinois Cleveland, Ohio
Atelectasis Amebiasis
Trichomoniasis (Trichomonas vaginalis)
Colleen A. Ryan, MD African Trypanosomiasis (Sleeping Sickness;
Instructor in Psychiatry Trypanosoma brucei complex)
Harvard Medical School American Trypanosomiasis (Chagas Disease;
Medical Director, Psychiatry Inpatient Service Trypanosoma cruzi)
Boston Children’s Hospital
Boston, Massachusetts Denise A. Salerno, MD, FAAP
Motor Disorders and Habits Professor of Clinical Pediatrics
Temple University School of Medicine
H.P.S. Sachdev, MD, FIAP, FAMS, Philadelphia, Pennsylvania
FRCPCH Nonbacterial Food Poisoning
Senior Consultant
Departments of Pediatrics and Clinical Edsel Maurice T. Salvana, MD
Epidemiology Clinical Associate Professor of Medicine
Sitaram Bhartia Institute of Science and Research University of the Philippines College of Medicine
New Delhi, India Director, Institute of Molecular Biology and
Vitamin B Complex Deficiencies and Excess Biotechnology
Vitamin C (Ascorbic Acid) National Institutes of Health
Manila, The Philippines;
Ramesh C. Sachdeva, MD, PhD, FAAP, Adjunct Professor of Global Health
FCCM University of Pittsburgh School of Medicine
Professor of Pediatrics (Critical Care) Pittsburgh, Pennsylvania
Medical College of Wisconsin Amebiasis
Milwaukee, Wisconsin; Trichomoniasis (Trichomonas vaginalis)
Associate Executive Director African Trypanosomiasis (Sleeping Sickness;
Medical Director, Quality Initiatives Trypanosoma brucei complex)
Director, Department of Subspecialty Pediatrics American Trypanosomiasis (Chagas Disease;
American Academy of Pediatrics Trypanosoma cruzi)
Elk Grove Village, Illinois
Quality and Safety in Healthcare for Children Hugh A. Sampson, MD
Kurt Hirschhorn Professor of Pediatrics
Manish Sadarangani, BM BCh, DPhil, Jaffe Food Allergy Institute
MRCPCH Icahn School of Medicine at Mount Sinai
Clinical Lecturer and Honorary Specialist Registrar New York, New York
Paediatric Infectious Diseases and Immunology Anaphylaxis
Children’s Hospital Food Allergy and Adverse Reactions to Foods
Oxford, United Kingdom
Neisseria meningitidis (Meningococcus) Thomas J. Sandora, MD, MPH
Assistant Professor of Pediatrics
Rebecca E. Sadun, MD, PhD Harvard Medical School
Adult and Pediatric Rheumatology Fellow Medical Director, Infection Prevention and Control
Departments of Medicine and Pediatrics Division of Infectious Diseases
Duke University School of Medicine Boston Children’s Hospital
Durham, North Carolina Boston, Massachusetts
Systemic Lupus Erythematosus Community-Acquired Pneumonia
Mustafa Sahin, MD, PhD Tracy L. Sandritter, PharmD
Associate Professor of Neurology Pharmacy Resident
Harvard Medical School Transplant Pharmacy
F.M. Kirby Neurobiology Center Children’s Mercy Hospitals and Clinics
Boston Children’s Hospital Kansas City, Missouri
Boston, Massachusetts Principles of Drug Therapy
Neurocutaneous Syndromes
Wudbhav N. Sankar, MD
Assistant Professor
Department of Orthopaedic Surgery
University of Pennsylvania Perelman School of
Medicine
Attending Orthopaedic Surgeon
Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania
The Hip
Eric J. Sarkissian, MD
Ben Fox Clinical Fellow
Department of Orthopaedics
Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania
The Knee
Ajit A. Sarnaik, MD
Assistant Professor
Department of Pediatrics
Wayne State University School of Medicine
Associate Director, Pediatric Residency Program
Children’s Hospital of Michigan
Detroit, Michigan
Respiratory Distress and Failure
Ashok P. Sarnaik, MD
Professor and Interim Chair
Department of Pediatrics
Wayne State University School of Medicine
Pediatrician in Chief
Children’s Hospital of Michigan
Detroit, Michigan
Respiratory Distress and Failure
Respiratory Pathophysiology and Regulation
Harvey B. Sarnat, MD, MS, FRCPC
Professor of Pediatrics, Pathology
(Neuropathology), and Clinical Neurosciences
Division of Pediatric Neurology
University of Calgary Faculty of Medicine
Alberta Children’s Hospital
Calgary, Alberta, Canada
Evaluation and Investigation (Neuromuscular
Disorders)
Developmental Disorders of Muscle
Muscular Dystrophies
Endocrine and Toxic Myopathies
Metabolic Myopathies
Disorders of Neuromuscular Transmission and of
Motor Neurons
Hereditary Motor-Sensory Neuropathies
Toxic Neuropathies
Autonomic Neuropathies
Guillain-Barré Syndrome
Bell Palsy
Minnie M. Sarwal, MD, PhD, FRCP,
DCH
Professor, Transplant Nephrology and Pediatrics
California Pacific Medical Center
Director, The BIOMARC Institute for Personalized
Medicine, Sutter Health Care
Director, The Sarwal Lab, CPMC-Research
Institute
San Francisco, California;
Consulting Professor
Stanford University
Palo Alto, California
Renal Transplantation
Laura E. Schanberg, MD
Professor of Pediatrics
Duke University School of Medicine
Co-Chief, Division of Pediatric Rheumatology
Duke University Medical Center
Durham, North Carolina
Systemic Lupus Erythematosus
Musculoskeletal Pain Syndromes
 Contributors xxix

Mark R. Schleiss, MD J. Paul Scott, MD Ala Shaikhkhalil, MD

Professor of Pediatrics Professor of Pediatrics Fellow
American Legion and Auxiliary Heart Foundation Division of Pediatric Hematology/Oncology Division of Gastroenterology, Hepatology, and
Research Chair Medical College of Wisconsin Nutrition
Director, Division of Pediatric Infectious Diseases Blood Center of Southeastern Wisconsin Children’s Hospital of Philadelphia
and Immunology Milwaukee, Wisconsin Philadelphia, Pennsylvania
University of Minnesota School of Medicine Hemostasis Nutritional Requirements
Minneapolis, Minnesota Hereditary Clotting Factor Deficiencies (Bleeding Feeding Healthy Infants, Children, and Adolescents
Principles of Antibacterial Therapy Disorders)
Principles of Antiviral Therapy von Willebrand Disease Raanan Shamir, MD
Principles of Antiparasitic Therapy Hereditary Predisposition to Thrombosis Professor of Pediatrics
Thrombotic Disorders in Children Sackler Faculty of Medicine
Nina F. Schor, MD, PhD Postneonatal Vitamin K Deficiency Tel-Aviv University
William H. Eilinger Professor and Chair Liver Disease Tel-Aviv, Israel;
Department of Pediatrics Acquired Inhibitors of Coagulation Chairman, Institute of Gastroenterology, Nutrition,
Professor, Department of Neurology Disseminated Intravascular Coagulation and Liver Diseases
Pediatrician-in-Chief Platelet and Blood Vessel Disorders Schneider Children’s Medical Center of Israel
Golisano Children’s Hospital Petach Tikvah, Israel
University of Rochester Medical Center Patrick C. Seed, MD, PhD Intestinal Infections and Infestations Associated with
Rochester, New York Associate Professor of Pediatrics Malabsorption
Neurologic Evaluation Division of Pediatric Infectious Diseases Chronic Malnutrition
Assistant Professor of Molecular Genetics and
Bill J. Schroeder, DO Microbiology Andi L. Shane, MD, MPH, MSc
Pediatric Emergency Medicine Duke University Medical Center Associate Professor of Pediatrics
Advocate Christ Medical Center Durham, North Carolina Division of Pediatric Infectious Diseases
Oak Lawn, Illinois The Microbiome and Pediatric Health Emory University School of Medicine
Envenomations Atlanta, Georgia
George B. Segel, MD Infections of the Neonatal Infant
James W. Schroeder Jr., MD, FACS, Professor of Medicine
FAAP Professor Emeritus of Pediatrics Bruce K. Shapiro, MD
Associate Professor University of Rochester Medical Center Professor of Pediatrics
Department of Otolaryngology—Head and Neck Rochester, New York The Arnold J. Capute MD, MPH Chair in
Surgery Definitions and Classification of Hemolytic Anemias Neurodevelopmental Disabilities
Northwestern University Feinberg School of Hereditary Spherocytosis The Johns Hopkins University School of Medicine
Medicine Hereditary Elliptocytosis Vice-President, Training
Ann & Robert H. Lurie Children’s Hospital of Hereditary Stomatocytosis Kennedy Krieger Institute
Chicago Paroxysmal Nocturnal Hemoglobinuria and Baltimore, Maryland
Chicago, Illinois Acanthocytosis Intellectual Disability
Congenital Anomalies of the Larynx, Trachea, and Enzymatic Defects
Bronchi Hemolytic Anemias Resulting from Extracellular Amanda N. Shaw, MD
Foreign Bodies in the Airway Factors—Immune Hemolytic Anemias Pediatric Endocrinology Fellow
Laryngotracheal Stenosis and Subglottic Stenosis Hemolytic Anemias Secondary to Other University of Texas Health Sciences Center
Neoplasms of the Larynx, Trachea, and Bronchi Extracellular Factors Houston, Texas
Campylobacter
Mark A. Schuster, MD, PhD Ernest G. Seidman, MDCM, FRCPC, Aeromonas and Plesiomonas
William Berenberg Professor of Pediatrics FACG
Harvard Medical School Professor of Medicine and Pediatrics Bennett A. Shaywitz, MD
Chief of General Pediatrics and Vice-Chair for Bruce Kaufman Endowed Chair in IBD Charles and Helen Schwab Professor in Dyslexia
Health Policy McGill University Faculty of Medicine and Learning Development
Department of Medicine Director, McGill Centre of IBD Co-Director, Center for Dyslexia and Creativity
Children’s Hospital Boston McGill University Health Center Chief, Child Neurology
Boston, Massachusetts Montreal, Quebec, Canada Yale University School of Medicine
Gay, Lesbian, and Bisexual Adolescents Immunodeficiency Disorders New Haven, Connecticut
Immunoproliferative Small Intestinal Disease Dyslexia
Gordon E. Schutze, MD Malabsorption in Eosinophilic Gastroenteritis
Executive Vice-Chairman Malabsorption in Inflammatory Bowel Disease Sally E. Shaywitz, MD
Professor of Pediatrics Audrey G. Ratner Professor in Learning
Martin I. Lorin MD Chair in Medical Education Janet R. Serwint, MD Development
Vice-President of International Medical Programs Professor Co-Director, Center for Dyslexia and Creativity
Baylor International Pediatric AIDS Initiative Department of Pediatrics Department of Pediatrics
Baylor College of Medicine Johns Hopkins University School of Medicine Yale University School of Medicine
Texas Children’s Hospital Baltimore, Maryland New Haven, Connecticut
Houston, Texas Loss, Separation, and Bereavement Dyslexia
Actinomyces
Nocardia Dheeraj Shah, MD, FIAP, MAMS Philip M. Sherman, MD, FRCP(C),
Tularemia (Francisella tularensis) Professor FAAP
Brucella Department of Pediatrics Professor of Paediatrics, Microbiology, and
University College of Medical Sciences Dentistry
Daryl A. Scott, MD, PhD Guru Teg Bahadur Hospital University of Toronto Faculty of Medicine
Associate Professor New Delhi, India Division of Gastroenterology, Hepatology, and
Department of Molecular and Human Genetics Vitamin B Complex Deficiencies and Excess Nutrition
Baylor College of Medicine Vitamin C (Ascorbic Acid) Senior Scientist, Cell Biology Research Program
Houston, Texas The Hospital for Sick Children
The Genetic Approach in Pediatric Medicine Toronto, Ontario, Canada
The Human Genome Other Malabsorptive Syndromes
Patterns of Genetic Transmission
xxx Contributors

Benjamin L. Shneider, MD Anne Slavotinek, MBBS, PhD David A. Spiegel, MD

Professor of Pediatrics Professor of Clinical Pediatrics Associate Professor
University of Pittsburgh School of Medicine University of California, San Francisco Department of Orthopaedic Surgery
Director, Pediatric Hepatology San Francisco, California University of Pennsylvania Perelman School of
Children’s Hospital of Pittsburgh of UPMC Dysmorphology Medicine
Pittsburgh, Pennsylvania Attending Orthopaedic Surgeon
Autoimmune Hepatitis Thomas L. Slovis, MD Children’s Hospital of Philadelphia
Professor Emeritus of Radiology and Pediatrics Philadelphia, Pennsylvania
Stanford T. Shulman, MD Wayne State University School of Medicine Hypermobile Pes Planus (Flexible Flatfeet)
Virginia H. Rogers Professor of Pediatric Infectious Department of Pediatric Imaging Toe Deformities
Diseases Children’s Hospital of Michigan Shoes
Northwestern University Feinberg School of Detroit, Michigan The Spine
Medicine Biologic Effects of Radiation on Children The Neck
Chief, Division of Infectious Diseases
Ann & Robert H. Lurie Children’s Hospital of P. Brian Smith, MD, MHS, MPH Helen Spoudeas, MD
Chicago Associate Professor of Pediatrics Honorary Senior Lecturer in Paediatric
Chicago, Illinois Division of Neonatology Endocrinology
Group A Streptococcus Duke University School of Medicine University College London
Durham, North Carolina Consultant in Neuro-Endocrine Late Effects of
Scott H. Sicherer, MD Candida Childhood Cancer
Elliot and Roslyn Jaffe Professor of Pediatrics, University College London Hospital
Allergy, and Immunology Mary Beth F. Son, MD Great Ormond Street Hospital
Jaffe Food Allergy Institute Instructor in Pediatrics London, United Kingdom
Icahn School of Medicine at Mount Sinai Department of Pediatrics Diarrhea from Neuroendocrine Tumors
New York, New York Harvard Medical School
Allergy and the Immunologic Basis of Atopic Disease Staff Physician, Division of Immunology Jürgen W. Spranger, MD
Diagnosis of Allergic Disease Boston Children’s Hospital Professor Emeritus of Pediatrics
Principles of Treatment of Allergic Disease Boston, Massachusetts University of Mainz School of Medicine
Allergic Rhinitis Kawasaki Disease Children’s Hospital
Childhood Asthma Mainz, Germany
Atopic Dermatitis (Atopic Eczema) Laura Stout Sosinsky, PhD Mucopolysaccharidoses
Insect Allergy Senior Research Scientist
Ocular Allergies Early Childhood Development James E. Squires, MD
Urticaria (Hives) and Angioedema Child Trends, Inc. Pediatric Gastroenterology Fellow
Anaphylaxis Bethesda, Maryland Cincinnati Children’s Hospital Medical Center
Serum Sickness Childcare: How Pediatricians Can Support Children Cincinnati, Ohio
Food Allergy and Adverse Reactions to Foods and Families Manifestations of Liver Disease
Adverse Reactions to Drugs
Joseph D. Spahn, MD Rajasree Sreedharan, MBBS, DCH,
Richard Sills, MD Professor MRCPCH
Professor of Pediatrics Department of Pediatrics Assistant Professor of Clinical Pediatrics
Director, Pediatric Hematology/Oncology National Jewish Health University of Pennsylvania Perelman School of
Upstate Medical University University of Colorado School of Medicine Medicine
Syracuse, New York Denver, Colorado Division of Gastroenterology and Nutrition
Iron-Deficiency Anemia Childhood Asthma The Children’s Hospital of Philadelphia
Other Microcytic Anemias Philadelphia, Pennsylvania
Rivkie Spalter Tubular Function
Mark D. Simms, MD, MPH Director Renal Tubular Acidosis
Professor of Pediatrics Mequon Jewish Preschool Nephrogenic Diabetes Insipidus
Medical College of Wisconsin Mequon, Wisconsin Bartter and Gitelman Syndromes and Other
Medical Director The Reggio Emilia Educational Approach and Child Inherited Tubular Transport Abnormalities
Child Development Center Development and Learning Renal Failure
Children’s Hospital of Wisconsin
Milwaukee, Wisconsin Mark A. Sperling, MD Raman Sreedharan, MD, DCH,
Language Development and Communication Professor and Chair Emeritus MRCPCH
Disorders Department of Pediatrics Clinical Assistant Professor of Pediatrics
Adoption University of Pittsburgh School of Medicine University of Pennsylvania Perelman School of
Division of Endocrinology, Metabolism, and Medicine
Eric A.F. Simões, MBBS, DCH, MD Diabetes Mellitus EHR Medical Director, Specialty Care
Professor of Pediatrics Children’s Hospital of Pittsburgh The Children’s Hospital of Philadelphia
University of Colorado School of Medicine Pittsburgh, Pennsylvania Philadelphia, Pennsylvania
Professor of Epidemiology Hypoglycemia Major Symptoms and Signs of Digestive Tract
Center for Global Health Disorders
Colorado School of Public Health Robert L. Spicer, MD Functional Abdominal Pain (Nonorganic Chronic
Division of Infectious Diseases Professor of Pediatrics Abdominal Pain)
The Children’s Hospital University of Nebraska Medical Center College of
Aurora, Colorado Medicine Nivedita Srinivas, MD
Polioviruses Clinical Professor of Pediatrics Clinical Instructor in Pediatrics
Creighton University School of Medicine Division of Pediatric Infectious Diseases
Kari A. Simonsen, MD Clinical Service Chief, Cardiology Stanford University School of Medicine
Assistant Professor of Pediatrics Children’s Hospital and Medical Center Stanford, California
Division of Infectious Diseases Omaha, Nebraska Central Nervous System Infections
University of Nebraska Medical Center Diseases of the Myocardium
Omaha, Nebraska Diseases of the Pericardium
Leptospira Tumors of the Heart
 Contributors xxxi

Margaret M. Stager, MD, FAAP Charles A. Stanley, MD Ronald G. Strauss, MD

Associate Professor Professor of Pediatrics Professor Emeritus
Department of Pediatrics University of Pennsylvania Perelman School of Departments of Pediatrics and Pathology
Case Western Reserve University School of Medicine University of Iowa Carver College of Medicine
Medicine Division of Endocrinology Iowa City, Iowa
Director, Division of Adolescent Medicine Children’s Hospital of Philadelphia Red Blood Cell Transfusions and Erythropoietin
MetroHealth Medical Center Philadelphia, Pennsylvania Therapy
Cleveland, Ohio Disorders of Mitochondrial Fatty Acid ß-Oxidation Platelet Transfusions
Violent Behavior Neutrophil (Granulocyte) Transfusions
Substance Abuse Bonita F. Stanton, MD Plasma Transfusions
Vice-Dean of Research Risks of Blood Transfusions
Erin D. Stahl, MD Professor of Pediatrics
Assistant Professor Wayne State University School of Medicine Gina S. Sucato, MD, MPH
Department of Ophthalmology Detroit, Michigan Associate Professor of Pediatrics
University of Missouri—Kansas City School of Overview of Pediatrics University of Pittsburgh School of Medicine
Medicine Cultural Issues in Pediatric Care Fellowship Director, Division of Adolescent
Children’s Mercy Hospital Childhood Psychoses Medicine
Kansas City, Missouri Catatonia in Children and Adolescents Children’s Hospital of Pittsburgh of UPMC
Growth and Development (Eye) Pittsburgh, Pennsylvania
Examination of the Eye Jeffrey R. Starke, MD Menstrual Problems
Abnormalities of Refraction and Accommodation Professor of Pediatrics
Disorders of Vision Division of Infectious Diseases Frederick J. Suchy, MD
Abnormalities of Pupil and Iris Baylor College of Medicine Professor of Pediatrics
Disorders of Eye Movement and Alignment Infection Control Officer Associate Dean for Child Health Research
Abnormalities of the Lids Texas Children’s Hospital University of Colorado
Disorders of the Lacrimal System Houston, Texas Denver, Colorado;
Disorders of the Conjunctiva Tuberculosis (Mycobacterium tuberculosis) Chief Research Officer and Director
Abnormalities of the Cornea Children’s Hospital Colorado Research Institute
Abnormalities of the Lens Barbara W. Stechenberg, MD Aurora, Colorado
Disorders of the Uveal Tract Professor of Pediatrics Autoimmune Hepatitis
Disorders of the Retina and Vitreous Tufts University School of Medicine Drug- and Toxin-Induced Liver Injury
Abnormalities of the Optic Nerve Boston, Massachusetts; Fulminant Hepatic Failure
Childhood Glaucoma Pediatric Infectious Diseases Cystic Diseases of the Biliary Tract and Liver
Orbital Abnormalities Baystate Children’s Hospital Diseases of the Gallbladder
Orbital Infections Springfield, Massachusetts Portal Hypertension and Varices
Injuries to the Eye Bartonella
Britta M. Svoren, MD
Amy P. Stallings, MD William J. Steinbach, MD Assistant Professor of Pediatrics
Assistant Professor of Pediatrics Associate Professor of Pediatrics and Molecular Division of Pediatric Endocrinology
Division of Pediatric Allergy and Immunology Genetics and Microbiology University of Rochester Medical Center
Duke University School of Medicine Duke University Medical Center Rochester, New York
Durham, North Carolina Durham, North Carolina Diabetes Mellitus
Urticaria (Hives) and Angioedema Principles of Antifungal Therapy
Aspergillus Stephen J. Swanson, MD
Virginia A. Stallings, MD Associate Professor of Pediatrics
Professor of Pediatrics Janet Stewart, MD Divisions of Global Pediatrics and Pediatric
Division of Gastroenterology, Hepatology, and Associate Professor Emerita Infectious Diseases
Nutrition Department of Pediatrics University of Minnesota Medical School
University of Pennsylvania Perelman School of University of Colorado School of Medicine Minneapolis, Minnesota
Medicine Spina Bifida Clinic Health Advice for Children Traveling Internationally
Director, Nutrition Center Children’s Hospital Colorado
Children’s Hospital of Philadelphia Denver, Colorado Moira Szilagyi, MD, PhD
Philadelphia, Pennsylvania Meningomyelocele (Spina Bifida) Professor of Pediatrics
Nutritional Requirements University of Rochester School of Medicine
Feeding Healthy Infants, Children, and Adolescents Barbara J. Stoll, MD Rochester, New York
George W. Brumley Jr. Professor and Chair Foster and Kinship Care
Kathryn C. Stambough, MD Department of Pediatrics
Resident Physician Emory University School of Medicine Libo Tan, PhD
Department of Obstetrics and Gynecology Director, The Pediatric Center of Emory and Postdoctoral Fellow
Washington University School of Medicine in St. Children’s Healthcare of Atlanta Department of Nutritional Sciences
Louis Atlanta, Georgia The Pennsylvania State University
St. Louis, Missouri Infections of the Neonatal Infant University Park, Pennsylvania
History and Physical Examination (Gynecology) Vitamin A Deficiencies and Excess
Gregory A. Storch, MD
Lawrence R. Stanberry, MD, PhD Professor of Pediatrics Robert R. Tanz, MD
Reuben S. Carpentier Professor and Chairman Washington University in St. Louis School of Professor of Pediatrics
Department of Pediatrics Medicine Division of Academic General Pediatrics and
Columbia University College of Physicians and St. Louis, Missouri Primary Care
Surgeons Diagnostic Microbiology Northwestern University Feinberg School of
New York, New York Polyomaviruses Medicine
Herpes Simplex Virus Ann & Robert H. Lurie Children’s Hospital of
Chicago
Chicago, Illinois
Acute Pharyngitis
xxxii Contributors

Nidale Tarek, MD Riccardo Troncone, MD Jon A. Vanderhoof, MD

Assistant Professor of Pediatrics Professor and Director Professor Emeritus of Pediatrics
University of Texas MD Anderson Cancer Center Department of Pediatrics University of Nebraska Medical Center
Houston, Texas University of Naples Federico II Omaha, Nebraska;
Retinoblastoma Napoli, Italy Lecturer in Pediatrics, Harvard Medical School
Neoplasms of the Liver Celiac Disease (Gluten-Sensitive Enteropathy) Staff Gastroenterologist, Children’s Hospital Boston
Boston, Massachusetts;
Cynthia J. Tifft, MD, PhD David G. Tubergen, MD Vice-President for Global Medical Affairs
National Human Genome Research Institute Medical Director for Host Program Mead Johnson Nutritionals
National Institutes of Health MD Anderson Physicians Network Evansville, Indiana
Bethesda, Maryland Houston, Texas Short Bowel Syndrome
Genetic Approaches to Rare and Undiagnosed The Leukemias
Diseases George F. Van Hare, MD
Margaret A. Turk, MD Louis Larrick Ward Professor of Pediatrics
Norman Tinanoff, DDS, MS Professor Director, Division of Pediatric Cardiology
Professor Departments of Physical Medicine and Washington University in St. Louis
Department of Orthodontics and Pediatric Rehabilitation and Pediatrics St. Louis Children’s Hospital
Dentistry State University of New York St. Louis, Missouri
Chief, Division of Pediatric Dentistry SUNY Upstate Medical University Syncope
University of Maryland School of Dentistry Syracuse, New York Disturbances of Rate and Rhythm of the Heart
Baltimore, Maryland Health and Wellness for Children with Disabilities
Development and Developmental Anomalies of the Jakko van Ingen, MD, PhD
Teeth David A. Turner, MD Clinical Microbiology Resident
Disorders of the Oral Cavity Associated with Other Associate Professor Radboud University Medical Centre
Conditions Department of Pediatrics Nijmegen, The Netherlands
Malocclusion Duke University School of Medicine Nontuberculous Mycobacteria
Cleft Lip and Palate Director, Pediatric Critical Care Fellowship
Syndromes with Oral Manifestations Program Heather A. Van Mater, MD, MS
Dental Caries Medical Director, Pediatric Intensive Care Unit Assistant Professor of Pediatrics
Periodontal Diseases Duke University Medical Center Duke University School of Medicine
Dental Trauma Durham, North Carolina Division of Pediatric Rheumatology
Common Lesions of the Oral Soft Tissues Shock Duke University Health System
Diseases of the Salivary Glands and Jaws Durham, North Carolina
Diagnostic Radiology in Dental Assessment Christina Ullrich, MD, MPH Scleroderma and Raynaud Phenomenon
Assistant Professor in Pediatrics Central Nervous System Vasculitis
James K. Todd, MD Department of Psychosocial Oncology and
Professor of Pediatrics and Microbiology Palliative Care Dick van Soolingen, PhD
University of Colorado School of Medicine Department of Pediatric Hematology/Oncology Professor of Translational Tuberculosis Research
Professor of Epidemiology Harvard Medical School Radboud University Medical Centre
University of Colorado School of Public Health Boston Children’s Hospital Nijmegen, The Netherlands;
Director, Epidemiology and Clinical Microbiology Dana-Farber Cancer Institute Head, Mycobacteria Reference Laboratory
Children’s Hospital Colorado Boston, Massachusetts National Institute for Public Health and the
Aurora, Colorado Pediatric Palliative Care Environment (RIVM)
Staphylococcus Bilthoven, The Netherlands
David K. Urion, MD Nontuberculous Mycobacteria
Lucy S. Tompkins, MD, PhD Charles F. Barlow Chair
Lucy Becker Professor of Medicine Department of Neurology Christine VanTubbergen, BA
Division of Infectious Diseases/Geographic Harvard University Former Coordinator, National Collaborative
Medicine Boston Children’s Hospital Congenital Toxoplasmosis Study
Stanford University School of Medicine Boston, Massachusetts The University of Chicago School of Medicine
Stanford, California Attention-Deficit/Hyperactivity Disorder Chicago, Illinois;
Legionella Current ORISE Fellow
Douglas Vanderbilt, MD Centers for Disease Control and Prevention
Richard L. Tower II, MD, MS Associate Professor of Clinical Pediatrics Atlanta, Georgia
Assistant Professor of Pediatrics Associate Professor of Occupational Science/ Toxoplasmosis (Toxoplasma gondii)
Division of Pediatric Hematology, Oncology, and Occupational Therapy
Transplant University of Southern California Keck School of Scott K. Van Why, MD
Medical College of Wisconsin Medicine Professor of Pediatrics
Milwaukee, Wisconsin Director, MCHB Developmental-Behavioral Medical College of Wisconsin
Anatomy and Function of the Lymphatic System Pediatrics Training Program Wauwatosa, Wisconsin
Abnormalities of Lymphatic Vessels Children’s Hospital Los Angeles Membranous Nephropathy
Lymphadenopathy Director, California Leadership Education in Membranoproliferative Glomerulonephritis
Neurodevelopmental Disabilities Program Henoch-Schönlein Purpura Nephritis
Michael L. Trieu, MD University Center for Excellence in Developmental Rapidly Progressive (Crescentic) Glomerulonephritis
Instructor in Psychiatry Disabilities Goodpasture Disease
Harvard Medical School Los Angeles, California Hemolytic-Uremic Syndrome
Assistant in Psychiatry Bullying, Cyberbullying, and School Violence
Boston Children’s Hospital
Boston, Massachusetts
Motor Disorders and Habits
Autism Spectrum Disorder
Childhood Psychoses
Schizophrenia Spectrum and Other Psychotic
Disorders
Acute Phobic Hallucinations of Childhood
 Contributors xxxiii

Andrea Velardi, MD Kelly J. Walkovich, MD Jason B. Weinberg, MD

Professor of Hematology Assistant Professor of Pediatrics and Assistant Professor of Pediatrics and Microbiology
Division of Hematology and Clinical Immunology Communicable Diseases and Immunology
University of Perugia Division of Pediatric Hematology/Oncology Division of Pediatric Infectious Diseases
Ospedale Santa Maria della Misericordia University of Michigan Medical School University of Michigan Medical School
Perugia, Italy Ann Arbor, Michigan Ann Arbor, Michigan
Principles and Clinical Indications of Hematopoietic Leukopenia Adenoviruses
Stem Cell Transplantation Leukocytosis
Hematopoietic Stem Cell Transplantation from Kathryn L. Weise, MD, MA
Alternative Sources and Donors Rebecca Wallihan, MD Program Director, Cleveland Fellowship in
Graft-Versus-Host Disease, Rejection, and Assistant Professor of Pediatrics Advanced Bioethics
Venoocclusive Disease Section of Infectious Diseases and Immunology Department of Bioethics
Infectious Complications of Hematopoietic Stem Cell The Ohio State University College of Medicine The Cleveland Clinic Foundation
Transplantation Nationwide Children’s Hospital Cleveland, Ohio
Late Effects of Hematopoietic Stem Cell Columbus, Ohio Ethics in Pediatric Care
Transplantation Genital Mycoplasmas (Mycoplasma hominis,
Mycoplasma genitalium, and Ureaplasma Pamela F. Weiss, MD, MSCE
Elliott P. Vichinsky, MD urealyticum) Assistant Professor of Pediatrics
Professor of Pediatrics University of Pennsylvania Perelman School of
University of California, San Francisco Heather J. Walter, MD, MPH Medicine
San Francisco, California; Professor of Psychiatry and Pediatrics Division of Rheumatology
Medical Director Vice-Chair, Department of Psychiatry Children’s Hospital of Philadelphia
Hematology/Oncology Programs Boston University School of Medicine Philadelphia, Pennsylvania
Children’s Hospital of Oakland Chief, Child and Adolescent Psychiatry Ankylosing Spondylitis and Other
Oakland, California Boston Medical Center Spondyloarthritides
Hemoglobinopathies Senior Lecturer on Psychiatry Reactive and Postinfectious Arthritis
Harvard Medical School
Brian P. Vickery, MD Senior Associate in Psychiatry Martin E. Weisse, MD
Assistant Professor of Pediatrics Boston Children’s Hospital Chief, Department of Pediatrics
University of North Carolina at Chapel Hill School Boston, Massachusetts Tripler Army Medical Center
of Medicine Assessment and Interviewing Honolulu, Hawaii;
Chapel Hill, North Carolina Psychological Treatment of Children and Adolescents Professor of Pediatrics
Eosinophils Motor Disorders and Habits Uniformed Services University of the Health
Psychopharmacology Sciences
Bernadette E. Vitola, MD, MPH Psychotherapy Bethesda, Maryland
Assistant Professor of Pediatrics Psychiatric Hospitalization Malassezia
Medical College of Wisconsin Mood Disorders Primary Amebic Meningoencephalitis
Children’s Hospital of Wisconsin Suicide and Attempted Suicide
Milwaukee, Wisconsin Disruptive, Impulse-Control, and Conduct Disorders Lawrence Wells, MD
Liver Disease Associated with Systemic Disorders Autism Spectrum Disorder Associate Professor
Childhood Psychoses Department of Orthopaedic Surgery
Judith A. Voynow, MD University of Pennsylvania Perelman School of
Professor of Pediatrics Julie Wang, MD Medicine
Virginia Commonwealth University Associate Professor of Pediatrics Attending Orthopaedic Surgeon
Edwin L. Kendig Jr. Chair, Division of Pediatric Jaffe Food Allergy Institute Children’s Hospital of Philadelphia
Pulmonology Icahn School of Medicine at Mount Sinai Philadelphia, Pennsylvania
Children’s Hospital of Richmond at VCU New York, New York Growth and Development
Richmond, Virginia Insect Allergy Evaluation of the Child
Cystic Fibrosis Anaphylaxis Torsional and Angular Deformities
The Hip
Linda A. Waggoner-Fountain, MD Stephanie M. Ware, MD, PhD, Common Fractures
Associate Professor of Pediatrics FACMG
Division of Infectious Diseases Associate Professor Jessica W. Wen, MD
University of Virginia Health System Department of Pediatrics Assistant Professor of Pediatrics
Charlottesville, Virginia University of Cincinnati College of Medicine University of Pennsylvania Perelman School of
Childcare and Communicable Diseases Co-Director, Cardiovascular Genetics Medicine
Associate Medical Director and Director of Attending Physician
Steven G. Waguespack, MD, FAAP, Research and Development The Children’s Hospital of Philadelphia
FACE The Heart Institute Diagnostic Laboratory Philadelphia, Pennsylvania
Professor and Deputy Department Chair Cincinnati Children’s Hospital Medical Center Chylous Ascites
Department of Endocrine Neoplasia and Cincinnati, Ohio Peritonitis
Hormonal Disorders Diseases of the Myocardium
University of Texas MD Anderson Cancer Center Diseases of the Pericardium Danielle Wendel, MD
Houston, Texas Tumors of the Heart Fellow
Thyroid Tumors Division of Gastroenterology, Hepatology, and
Adrenal Tumors Debra E. Weese-Mayer, MD Nutrition
Professor of Pediatrics Children’s Hospital of Philadelphia
David M. Walker, MD Northwestern University Feinberg School of Philadelphia, Pennsylvania
Division of Pediatric Emergency Medicine Medicine Feeding Healthy Infants, Children, and Adolescents
Yale University School of Medicine Division of Pediatric Neurology
New Haven, Connecticut Ann & Robert H. Lurie Children’s Hospital of
Principles Applicable to the Developing World Chicago
Chicago, Illinois
Congenital Central Hypoventilation Syndrome
xxxiv Contributors

Steven L. Werlin, MD Perrin C. White, MD Glenna B. Winnie, MD

Professor of Pediatrics (Gastroenterology) Professor of Pediatrics Director, Pediatric and Adolescent Sleep Center
The Medical College of Wisconsin Audre Newman Rapoport Distinguished Chair in Fairfax Neonatal Associates, PC
Milwaukee, Wisconsin Pediatric Endocrinology Fairfax, Virginia
Embryology, Anatomy, and Physiology (Pancreas) University of Texas Southwestern Medical Center Emphysema and Overinflation
Pancreatic Function Tests Dallas, Texas α1-Antitrypsin Deficiency and Emphysema
Disorders of the Exocrine Pancreas Physiology of the Adrenal Gland Pleurisy, Pleural Effusions, and Empyema
Treatment of Pancreatic Insufficiency Adrenocortical Insufficiency Pneumothorax
Pancreatitis Congenital Adrenal Hyperplasia and Related Pneumomediastinum
Pseudocyst of the Pancreas Disorders Hydrothorax
Pancreatic Tumors Cushing Syndrome Hemothorax
Primary Aldosteronism Chylothorax
Michael R. Wessels, MD Adrenocortical Tumors
John F. Enders Professor of Pediatrics Pheochromocytoma Harland S. Winter, MD
Professor of Medicine (Microbiology and Adrenal Masses Associate Professor of Pediatrics
Immunobiology) Harvard Medical School
Harvard Medical School John V. Williams, MD Director, Pediatric Inflammatory Bowel Disease
Chief, Division of Infectious Diseases Assistant Professor of Pediatrics and of Pathology, Center
Boston Children’s Hospital Microbiology, and Immunology MassGeneral Hospital for Children
Boston, Massachusetts Division of Pediatric Infectious Disease Boston, Massachusetts
Group B Streptococcus Vanderbilt University School of Medicine Chronic Diarrhea
Nashville, Tennessee
Ralph F. Wetmore, MD Adenoviruses Paul H. Wise, MD, MPH
Professor Rhinoviruses Richard E. Behrman Professor of Child Health and
Department of Otorhinolaryngology—Head and The Common Cold Society
Neck Surgery Professor of Pediatrics
University of Pennsylvania Perelman School of Rodney E. Willoughby Jr., MD Stanford University School of Medicine
Medicine Professor of Pediatrics Director, Center for Policy, Outcomes, and
E. Mortimer Newlin Professor and Chief Medical College of Wisconsin Prevention
Division of Pediatric Otolaryngology Pediatric Infectious Diseases Senior Fellow, Freeman-Spogli Institute for
Children’s Hospital of Pennsylvania Children’s Hospital of Wisconsin International Studies
Philadelphia, Pennsylvania Milwaukee, Wisconsin Stanford, California
Tonsils and Adenoids Rabies Chronic Illness in Childhood

Randall C. Wetzel, MD Michael Wilschanski, MBBS Joshua Wolf, MBBS, FRACP

Chairman, Department of Anesthesiology Critical
Care Medicine
The Anne O’M elveney Wilson Professor of
Critical Care Medicine
Children’s Hospital of Los Angeles
Professor of Pediatrics and Anesthesiology
University of Southern California Keck School of
Medicine
Director, The Laura P. and Leland K. Whittier
Virtual PICU
Los Angeles, California
Anesthesia, Perioperative Care, and Sedation
Isaiah D. Wexler, MD, PhD
Associate Professor
Department of Pediatrics
Hadassah University Medical Center
Jerusalem, Israel
Effects of War on Children
Elizabeth A. Wharff, PhD, LICSW
Assistant Professor of Psychiatry
Harvard Medical School
Director, Emergency Psychiatry Service
Boston Children’s Hospital
Boston, Massachusetts
Suicide and Attempted Suicide
A. Clinton White Jr., MD
Paul R. Stalnaker MD Distinguished Professor of
Medicine
Director, Infectious Disease Division
University of Texas Medical Branch
Galveston, Texas
Adult Tapeworm Infections
Cysticercosis
Echinococcosis (Echinococcus granulosus and
Echinococcus multilocularis)
Professor of Pediatrics Assistant Member
The Hebrew University–Hadassah School of Department of Infectious Diseases
Medicine St. Jude’s Children’s Research Hospital
Director, Pediatric Gastroenterology Unit Memphis, Tennessee
Hadassah University Hospitals Infection Associated with Medical Devices
Jerusalem, Israel
Embryology, Anatomy, and Physiology (Pancreas) Joanne Wolfe, MD, MPH
Pancreatic Function Tests Associate Professor of Pediatrics
Disorders of the Exocrine Pancreas Harvard Medical School
Treatment of Pancreatic Insufficiency Chief, Division of Pediatric Palliative Care
Pancreatitis Dana-Farber Cancer Institute
Pseudocyst of the Pancreas Director, Pediatric Palliative Care
Pancreatic Tumors Boston Children’s Hospital
Boston, Massachusetts
Pamela Wilson, MD Pediatric Palliative Care
Associate Professor
Department of Physical Medicine and James B. Wood, MD
Rehabilitation Clinical Fellow
University of Colorado School of Medicine Pediatric Infectious Diseases
Children’s Hospital Colorado Vanderbilt University Medical Center
Denver, Colorado Nashville, Tennessee
Meningomyelocele (Spina Bifida) Streptococcus pneumoniae (Pneumococcus)
Samantha L. Wilson, PhD Laura L. Worth, MD, PhD
Associate Professor Associate Professor of Pediatrics
Department of Pediatrics University of Texas MD Anderson Cancer Center
Medical College of Wisconsin Center Medical Director
Children’s Hospital of Wisconsin The Children’s Cancer Hospital
Child Development Center, International Adoption Houston, Texas
Clinic Molecular and Cellular Biology of Cancer
Milwaukee, Wisconsin
Adoption Joseph L. Wright, MD, MPH
Professor and Chair
Jennifer J. Winell, MD Department of Pediatrics
Attending Orthopaedic Surgeon Professor of Emergency Medicine
Department of Orthopaedic Surgery Howard University College of Medicine
Children’s Hospital of Philadelphia Washington, DC
Philadelphia, Pennsylvania Emergency Medical Services for Children
The Foot and Toes
 Contributors xxxv

Terry W. Wright, PhD JiaDe Yu, MD Lonnie K. Zeltzer, MD

Associate Professor of Pediatrics Resident Physician Distinguished Professor
Division of Pediatric Infectious Diseases Department of Dermatology Departments of Anesthesiology, Psychiatry, and
University of Rochester School of Medicine and Medical College of Wisconsin Biobehavioral Sciences
Dentistry Children’s Hospital of Wisconsin David Geffen School of Medicine at UCLA
Rochester, New York Milwaukee, Wisconsin Director, Children’s Pain and Comfort Care
Pneumocystis jiroveci (Pneumocystis carinii) Diseases of Subcutaneous Tissue Program
Mattel Children’s Hospital UCLA
Eveline Y. Wu, MD Marc Yudkoff, MD Los Angeles, California
Assistant Professor William T. Grant Professor in Pediatrics Pediatric Pain Management
Department of Pediatrics University of Pennsylvania Perelman School of
Division of Allergy, Immunology, and Medicine Klaus-Peter Zimmer, MD
Rheumatology Institute for Translational Medicine and Abt. Allgemeine Pädiatrie und Neonatologie
University of North Carolina at Chapel Hill Therapeutics Zentrum für Kinderheilkunde und Jugendmedizin
Chapel Hill, North Carolina Division of Developmental and Behavioral Universitätsklinikum Gießen und Marburg GmbH
Juvenile Idiopathic Arthritis Pediatrics Gießen, Germany
Sarcoidosis Children’s Hospital of Philadelphia Rare Inborn Defects Causing Malabsorption
Philadelphia, Pennsylvania
Pablo Yagupsky, MD Urea Cycle and Hyperammonemia (Arginine, Naama Zoran, PhD
Professor of Pediatrics and Clinical Microbiology Citrulline, Ornithine) Developmental Psychologist
Goldman School of Medicine International Educational Systems Consultant
Ben-Gurion University of the Negev Peter E. Zage, MD, PhD Mequon, Wisconsin
Beer-Sheva, Israel Assistant Professor of Pediatrics The Reggio Emilia Educational Approach and Child
Kingella kingae Section of Pediatric Hematology/Oncology Development and Learning
Baylor College of Medicine
Michael Yaron, MD Houston, Texas Barry S. Zuckerman, MD
Professor Neuroblastoma Professor of Pediatrics and Chair Emeritus
Department of Emergency Medicine Boston University School of Medicine
University of Colorado School of Medicine Ramia Zakhour, MD Boston Medical Center
Aurora, Colorado Pediatric Infectious Diseases Fellow Boston, Massachusetts
Altitude-Associated Illness in Children (Acute University of Texas Health Sciences Center Impact of Violence on Children
Mountain Sickness) Houston, Texas
Yersinia
Ram Yogev, MD
Susan B. DePree Founders’ Board Professor of
Pediatrics
Northwestern University Feinberg School of
Medicine
Director, Pediatric, Adolescent, and Maternal HIV
Infection
Ann & Robert H. Lurie Children’s Hospital of
Chicago
Chicago, Illinois
Acquired Immunodeficiency Syndrome (Human
Immunodeficiency Virus)
Preface
Whoever saves one life it is considered as if they saved an entire world.
— Babylonian Talmud
The 20th edition of Nelson Textbook of Pediatrics continues in its tradi-
tion of being an essential resource for pediatricians as they diagnose
and treat the infants, children, and adolescents of the 21st century. The
20th edition has been thoroughly revised, updated, and edited to keep
up with the growing data accumulated from basic, clinical, and
population-based research. The promise that translational medicine
will improve the lives of all children is greater than ever. Knowledge of
human development, behavior, and diseases from the molecular to
sociologic levels is increasing at fantastic rates, leading to greater
understanding of health and illness in children and substantial
improvements in health quality for those who have access to health
care. These exciting scientific advances also provide hope to effectively
address prevention and treatment of new and emerging diseases
threatening children and their families.
The field of pediatrics encompasses advocacy for all children
throughout the world and must address societal inequalities of impor-
tant resources required for normal development, as well as protection
from natural and manmade disasters. Unfortunately, many children
throughout the world have not benefited from the significant advances
in the prevention and treatment of health-related problems, primarily
because of a lack of political will and misplaced priorities. For our
increasing knowledge to benefit all children and youth, medical
advances and good clinical practice must always be coupled with effec-
tive advocacy.
This new edition of Nelson Textbook of Pediatrics attempts to provide
the essential information that practitioners, house staff, medical stu-
dents, and other care providers involved in pediatric health care
throughout the world need to understand to effectively address the
enormous range of biologic, psychologic, and social problems that our
children and youth may face. Our goal is to be comprehensive yet
concise and reader friendly, embracing both the new advances in clini-
cal science and the time-honored art of pediatric practice.
The 20th edition is reorganized and revised from the previous edition.
There are many additions of new diseases and new chapters, as well as
xxxvi
substantial expansion or significant modification of others. In addition
many more tables, photographs, imaging studies, and illustrative
figures, as well as up-to-date references, have been added. Although,
to an ill child and his or her family and physician, even the rarest
disorder is of central importance, all health problems cannot possibly
be covered with the same degree of detail in one general textbook of
pediatrics. Thus, leading articles and subspecialty texts are referenced
and should be consulted when more information is desired.
The outstanding value of the 20th edition of the textbook is due to
its expert and authoritative contributors. We are all indebted to these
dedicated authors for their hard work, knowledge, thoughtfulness, and
good judgment. Our sincere appreciation also goes to Kate Dimock
and Jennifer Shreiner at Elsevier and to Carolyn Redman at the Pedi-
atric Department of the Medical College of Wisconsin. In addition, we
thank Barbara Ruggeri for her excellent library science skills and for
keeping us up to date with the literature. We have all worked hard to
produce an edition that will be helpful to those who provide care for
children and youth and to those desiring to know more about children’s
health worldwide.
In this edition we have had informal assistance from many faculty
and house staff of the departments of pediatrics at the Medical College
of Wisconsin, Wayne State University School of Medicine, University
of Pennsylvania School of Medicine, and University of Rochester
School of Medicine. The help of these individuals and of the many
practicing pediatricians from around the world who have taken the
time to offer thoughtful feedback and suggestions is always greatly
appreciated and helpful.
Last and certainly not least, we especially wish to thank our families
for their patience and understanding, without which this textbook
would not have been possible.
Robert M. Kliegman, MD
Bonita F. Stanton, MD
Joseph W. St Geme III, MD
Nina F. Schor, MD, PhD
lxviii Contents

VIDEOS
Video 304-1 Live Echinococcus granulosus protoscole,
Video 598-1 Severely limited level of consciousness and
movement disorder in a patient with anti-
NMDAR encephalitis after herpes simplex
encephalitis
Video 598-2 Improved level of consciousness in patient
shown in Video 598-1 following
immunotherapy
Video 598-3 Intact cognition in patient shown in Videos
598-1 and 598-2 after immunotherapy and
prolonged follow-up
Nelson
TEXTBOOK of
PEDIATRICS

The Field of Pediatrics
Chapter 1 available within these countries; and (9) political focus and stability.
Overview of Pediatrics
Bonita F. Stanton and Richard E. Behrman
Pediatrics is the only discipline dedicated to all aspects of the well-
being of infants, children, and adolescents, including their health; their
physical, mental, and psychologic growth and development; and their
opportunity to achieve full potential as adults. Pediatricians must be
concerned not only with particular organ systems and biologic pro-
cesses, but also with environmental, social, and political influences,
which have a major impact on the health and well-being of children
and their families.
Children cannot advocate for themselves. As the professionals whose
entire purpose is to advance the well-being of children, pediatricians
must be advocates for the individual child and for all children, irrespec-
tive of culture, religion, gender, race, or ethnicity or of local, state, or
national boundaries. The more politically, economically, or socially
disenfranchised a population or a nation is, the greater the need for
advocacy for children. The young are often among the most vulnerable
or disadvantaged in society and thus their needs require special atten-
tion. As divides between nations blur through modern transportation,
communication and economics, through global climate change,
through contemporary means of warfare, and through uneven develop-
ment within and across countries, a global, rather than a national,
perspective for the field of pediatrics becomes both a reality and a
necessity. The interrelation of health issues across the globe has achieved
widespread recognition in the wake of the SARS (severe acute respira-
tory syndrome) and AIDS epidemics, expansions in the pandemics of
cholera and West Nile virus, war and bioterrorism, the tsunami of 2004,
the global recession beginning in 2008, the “Arab Spring” beginning in
2010, and the growing severity of hurricanes and cyclones.
More than a century ago, pediatrics emerged as a medical specialty
in response to increasing awareness that the health problems of chil-
dren differ from those of adults and that a child’s response to illness
and stress varies with age. In 1959, the United Nations issued the
Declaration of the Rights of the Child, articulating the universal pre-
sumption that children everywhere have fundamental needs and rights.
VITAL STATISTICS ABOUT CHILD HEALTH
(See Also Chapter 1.1)
From 1990 to 2010, the world population grew at an annual rate
of 1.3% per yr, down from 1.8% annually during the prior 20 yr.
The annual growth rate from 2010 to 2030 is expected to further
decline to 0.9%. Worldwide, children younger than age 18 yr account
for 2.2 billion (30%) of the world’s 7.02 billion persons. In 2010, there
were an estimated 135 million births worldwide, 121 million (90%) of
which were in developing countries. India, with 27.2 million births
annually, is home to the largest number, followed by China at 16.5
million.
Despite global interconnectedness, the health problems of children
and youth vary widely between and within populations in the nations
of the world depending on a number of often interrelated factors. These
factors include (1) economic considerations (economic disparities); (2)
educational, social, and cultural considerations; (3) the prevalence and
ecology of infectious agents and their hosts; (4) climate and geography;
(5) agricultural resources and practices (nutritional resources); (6)
PART
I
stage of industrialization and urbanization; (7) the gene frequencies
for some disorders; (8) the health and social welfare infrastructure
The state of health of any community is defined by the incidence of
illness and by data from studies that show the changes that occur with
time and in response to programs of prevention, case finding, therapy,
and surveillance. To ensure that the needs of children and adults across
the globe were not obscured by local needs, in 2000 the international
community established 8 Millennium Development Goals (MDGs) to
be achieved by 2015 (http://www.countdown2015mnch.org). Although
all 8 MDGs impact child well-being, MDG 4 (“Reduce by two-thirds,
between 1990 and 2015, the under-five mortality rate”) is exclusively
focused on children.
Great strides have been made toward achieving the MDGs. Globally,
there has been a reduction in under-5 mortality since 1990 from 90 to
48 deaths per 1,000 live births, with a reduction from 15 to 6 deaths in
developed countries and from 99 to 53 deaths in developing countries.
With the exception of sub-Saharan Africa and Oceania, all global
regions reduced their under-5 mortality rate by more than half from
1990 to 2012. There were nearly 13 million under-5 deaths in 1990;
2006 marked the first year that there were fewer than 10 million deaths
(9.7 million), which further decreased to 9.0 million in 2007, 8.8
million in 2008, 7.6 million in 2010, and 6.6 million in 2012. Despite
these substantial successes, the annual rate of reduction in the global
under-5 mortality rate of 3.9% remains below the MDG targeted rate
of 4.4%, necessary to achieve the goal of a 2 3 reduction in the 1990 rate
by 2015 (Fig. 1-1).
The infant mortality rate (deaths of children <1 yr) accounts for 83%
of the under-5 mortality rate in industrialized countries, but only 64%
of the rate in the least-developed nations. Neonatal (<1 mo) death
contributes substantially to the under-5 mortality rate, growing in
proportion as the under-5 death rate decreases. The neonatal mortality
rate has been slower to decline. Globally, the neonatal mortality rate of
23 per 1,000 live births represents 57% of the infant mortality rate of
40 per 1,000 live births and 40% of the under-5 death rate (up from
37% in 1990). The neonatal mortality rate is responsible for 50% of the
under-5 mortality rate in industrialized nations, 40% of the rate in
developing countries, but only 33% in the least-developed countries.
Most of the decline in infant mortality in the United States and
other industrialized countries since 1970 is attributable to a decrease
in the birthweight-specific infant mortality rate related to neonatal
intensive care, not to the prevention of low-birthweight births (see
Chapter 93).
Across the globe, there are significant variations in infant mortality
rates by nation, by region, by economic status, and by level of industrial
development, the categorizations employed by the World Bank and the
United Nations (Table 1-1; see also Figs. 1-8 and 1-9). As of 2012 three
nations in the world still have an under-5 mortality rate of ≥150 per
1,000 live births (Sierra Leone, 182; Angola, 164, Chad, 150), with
an additional 13 nations having ≥100 deaths per 1,000 live births.
Although these 3 nations are among the poorest in the world, many of
their economic matches have enjoyed greater improvements in child
survival in recent years, demonstrating that economics are important
but that other factors, such as political will, are also important. Simi-
larly, in 2012, the United States, with one of the 10 highest gross
national incomes in the world, had an under-5 mortality rate of 7 per
1,000 live births; 39 nations had lower under-5 mortality rates, with 9
countries having a rate of 3 and 2 countries having a rate of 2 per 1,000
live births.
Causes of under-5 mortality differ markedly between developed and
developing nations. In developing countries, 66% of all deaths resulted
from infectious and parasitic diseases. Among the 42 countries having
1
2 Part I ◆ The Field of Pediatrics

Sub-Saharan Africa 90% of childhood deaths, diarrheal disease accounted for 22% of
177 deaths, pneumonia 21%, malaria 9%, AIDS 3%, and measles 1%. Neo-
98 natal causes contributed to 33%. The contribution for AIDS varies
Southern Asia greatly by country, being responsible for a substantial proportion of
126 deaths in some countries and negligible amounts in others. Likewise,
58
there is substantial co-occurrence of infections; a child may die with
Oceania
HIV, malaria, measles, and pneumonia. Infectious diseases are still
74
55 responsible for much of the mortality in developing countries. In the
Caucasus and Central Asia United States, pneumonia (and influenza) accounted for only 2% of
73 under-5 deaths, with only negligible contributions from diarrhea and
36 malaria. Unintentional injury is the most common cause of death
South-Eastern Asia among U.S. children ages 1-4 yr, accounting for approximately 33% of
71 deaths, followed by congenital anomalies (11%), homicides (9%), and
30 malignant neoplasms (8%). Other causes accounted for <5% of total
Western Asia mortality within this age group (Table 1-2). Although unintentional
65 injuries in developing countries are proportionately less important
25 causes of mortality than in developed countries, their absolute rates
Northern Africa and their contributions to morbidity are substantially greater.
73 Just as economic status of a country as a whole is closely correlated
22
with child survival, so too is relative wealth within a country. Poorer
Latin America and the Caribbean
children in nations worldwide have higher death rates than their
54
19 wealthier national counterparts (Fig. 1-2).
Eastern Asia Causes of death vary by developmental status of the nation. In the
53 United States, the 3 leading causes of death among infants were con-
14 genital anomalies, disorders related to gestation and low birthweight,
Developed regions and sudden infant death (see Table 1-2). By contrast, in developing
15 countries, the majority of infant deaths are caused by infectious dis-
6 eases; even in the neonatal period, 24% of deaths are caused by severe
Developing regions infections and 7% by tetanus. Although immunization rates remain
99 higher in industrialized nations compared to developing nations, this
53 gap is closing. In 2010, immunization percentage rates against diph-
0 50 100 150 200 theria, pertussis, tetanus, measles, and polio were in the mid-90s; com-
1990 2012 2015 target parable levels in developing countries were in the mid-80s, with rates
Figure 1-1 Despite substantial progress, the world is still falling short in the least-developed countries very close. In developing countries,
of the MDG child mortality target. Under-5 mortality rate per 1,000 29% of neonatal deaths are caused by birth asphyxia and 24% are
live births, 1990 and 2012 (deaths per 1,000 live births). (From Millen- caused by complications of prematurity.
nium Development Goals Report, 2014. New York, 2014, United A consistently robust predictor of infant mortality across the globe
Nations, p. 24.) is a poor level of maternal education (consequently, another of the
MDGs addresses the need for universal access to schooling for girls;
Fig. 1-3). Other maternal risk characteristics, such as unmarried status,
adolescence, and high parity, correlate with increased risk of postneo-
natal mortality and morbidity and low birthweight.

Table 1-1 Child Health Indicators Worldwide by Region

Mortality Rate by Yr Per 1,000 Live Births
GROSS LIFE PRIMARY
INFANT NEONATAL NATIONAL PER EXPECTANCY SCHOOL
UNDER-5 MORTALITY MORTALITY CAPITA INCOME AT BIRTH ATTENDANCE
1990 2012 1990 2012 2012 2012 2012 2008-2011
Sub-Saharan Africa 177 98 107 64 32 $1,397 56 yr 77%
Eastern and Southern Africa 163 77 101 51 28 $1,729 59 yr 87%
West and Central Africa 195 118 115 76 37 $1,071 54 yr 68%
Middle East and North Africa 71 30 53 24 15 — 71 yr 90%
South Asia 129 60 92 47 32 $1,440 67 yr 93%
East Asia and Pacific 58 20 44 17 11 $5,592 74 yr 97%
Latin America and Caribbean 54 19 43 16 10 $9,212 75 yr 95%
CEE/CIS 47 19 38 16 9 $8,727 70 yr 96%
Least-developed countries 172 85 107 58 30 $779 61 yr 81%
World 90 48 63 35 21 $10,132 71 yr 91%
CEE/CIS, Central and Eastern Europe/Commonwealth of Independent States (formerly the USSR).
Adapted from UNICEF: The state of the world’s children 2014: Statistical Table, New York, 2012, UNICEF, Table 1, p. 35.
 Chapter 1 ◆ Overview of Pediatrics 3

Table 1-2 Leading Causes of Death and Numbers of Deaths, According to Age: United States, 2010
AGE AND PERCENT OF
RANK ORDER CAUSE OF DEATH NUMBER TOTAL DEATHS
Under 1 yr All causes 24,586 100%
Congenital malformations, deformations, and chromosomal abnormalities 5,107 21%
Disorders related to short gestation and low birthweight, not elsewhere classified 4,148 17%
Sudden infant death syndrome 2,063 8%
Newborn affected by maternal complications of pregnancy 1,561 6%
Unintentional injuries 1,110 5%
Newborn affected by complications of placenta, cord, and membranes 1,030 4%
Bacterial sepsis of newborn 583 2%
Respiratory distress of newborn 514 2%
Diseases of the circulatory system 507 2%
Newborn affected by maternal complications of pregnancy 472 2%
1-4 yr All causes 4,316 100%
Unintentional injuries 1,394 32%
Congenital malformations, deformations, and chromosomal abnormalities 507 12%
Homicide 385 9%
Malignant neoplasms 346 8%
Diseases of heart 159 4%
Influenza and pneumonia 91 1%
Septicemia 62 1%
In situ neoplasms, benign neoplasms, and neoplasms of uncertain or unknown behavior 59 1%
Certain conditions originating in the perinatal period 52 1%
Chronic lower respiratory diseases 51 1%
5-14 yr All causes 5,279 100%
Unintentional injuries 1,643 31%
Malignant neoplasms 916 17%
Congenital malformations, deformations, and chromosomal abnormalities 298 6%
Suicide 274 5%
Homicide 261 5%
Diseases of heart 185 4%
Chronic lower respiratory diseases 133 3%
Cerebrovascular diseases 90 2%
In situ neoplasms, benign neoplasms, and neoplasms of uncertain or unknown behavior 82 2%
Influenza and pneumonia 71 1%
15-24 yr All causes 29,551 100%
Unintentional injuries 12,341 30%
Homicide 4,678 16%
Suicide 4,600 16%
Malignant neoplasms 1,604 5%
Diseases of heart 1,028 3%
Congenital malformations, deformations, and chromosomal abnormalities 412 1%
Cerebrovascular diseases 190 <1%
Influenza and pneumonia 181 <1%
Diabetes mellitus 165 <1%
Pregnancy, childbirth, and the puerperium 163 <1%
Adapted from National Center for Health Statistics: Health, United States, 2013: with special feature on prescription drugs. Hyattsville, MD, 2014, Department of
Health and Human Services, Table 23, p. 98.

THE CHANGING PEDIATRIC WORLD
A profound improvement in child health within industrialized nations
occurred in the 20th century with the introduction of antibacterial
disinfectants, antibiotic agents, and vaccines. Efforts to control infec-
tious diseases were complemented by better understanding of nutri-
tion. In the United States, Canada, and parts of Europe, new and
continuing discoveries in these areas led to establishment of public
well-child clinics for low-income families. Although the timing of
control of infectious disease was uneven around the globe, this focus
on control was accompanied by significant decreases in morbidity and
mortality in all countries. The smallpox eradication program of the
1970s resulted in the global eradication of smallpox in 1977. The intro-
duction in the 1970s of the Expanded Program of Immunizations
(universal vaccination against polio, diphtheria, measles, tuberculosis,
tetanus, and pertussis) by the World Health Organization (WHO) and
United Nations Children’s Fund (UNICEF) has resulted in an esti-
mated annual reduction of 1-2 million deaths per year globally. Rec-
ognizing the importance of prevention of infectious diseases to the
health of children, several countries among the 50 ranked by the World
Bank as among the poorest nations (per capita income <$750/yr) have
invested heavily in infectious disease control through the development
of internal vaccine production capability. From 2000 to 2010, globally
there was a 74% decline (with sub-Saharan Africa witnessing an 85%
decline) in deaths caused by measles as a result of increased vaccina-
tion. As diarrheal diseases continued through the mid-1970s to account
for ≈25% of infant and childhood deaths in developing countries
(~4 million deaths per year at that time), attention turned to the
development and utilization of oral resuscitation fluids to sustain chil-
dren through potentially life-threatening episodes of acute diarrheal
diseases. Oral rehydration solutions are largely credited with the
current reduction of diarrheal deaths annually to 1.5 million. Substan-
tial improvements have been witnessed in malaria control (global
decrease of incidence by 17% and mortality rate by 25% since 2000).
There have been substantial increases in the percent of households
having insecticide-treated bed nets and in treatment of children with
fever in endemic areas receiving antimalarial drugs.
In the later 20th century, with improved control of infectious dis-
eases (including the elimination of polio in the Western hemisphere)
4 Part I ◆ The Field of Pediatrics

Latin America and the Caribbean through both prevention and treatment, pediatric medicine in indus-
2.8 trialized nations increasingly turned its attention to a broad spectrum
Southern Asia of conditions. These included both potentially lethal conditions and
2.7 temporarily or permanently handicapping conditions; among these
disorders were leukemia, cystic fibrosis, diseases of the newborn infant,
Eastern Asia (excluding China) and South-Eastern Asia
congenital heart disease, mental retardation, genetic defects, rheumatic
2.3
diseases, renal diseases, and metabolic and endocrine disorders.
Northern Africa and Western Asia Increasing attention has also been given to behavioral and social
2.1 aspects of child health, ranging from reexamination of child-rearing
Caucasus and Central Asia practices to creation of major programs aimed at prevention and man-
1.7 agement of abuse and neglect of infants and children. Developmental
Sub-Saharan Africa
psychologists, child psychiatrists, neuroscientists, sociologists, anthro-
1.7 pologists, ethnologists, and others have brought us new insights into
human potential, including new views of the importance of the envi-
Developing regions ronmental circumstances during pregnancy, surrounding birth, and in
1.8 the early years of child rearing. The later 20th century witnessed the
0 1 3 beginning of nearly universal acceptance by pediatric professional
societies of attention to normal development, child rearing, and psy-
Higher mortality Equal Higher mortality among chosocial disorders across the continents. In the past decade, irrespec-
among the richest the poorest 20%
20%
tive of level of industrialization, nations have developed programs
addressing not only causes of mortality and physical morbidity (such
Note: Analysis is based on 73 developing countries with data on under- as infectious diseases and protein-calorie malnutrition), but also
five mortality rate by household’s wealth quintile, accounting for 71 factors leading to decreased cognition and thwarted psychosocial
percent of total births in developing countries in 2010.
development, including punitive child-rearing practices (whether at
Figure 1-2 Ratio of under-5 mortality rate for children from the home or in school) and wife abuse, child labor, undernutrition, war,
poorest 20% quintile of households to children from the richest 20% and poor-quality schooling. Obesity is recognized as a major health
of households, 2000/2010. (From Millennium Development Goals risk not only in industrialized nations, but increasingly in transitional
Report, 2012. New York, 2012, United Nations, p. 28.) countries. Progress at the turn of the 21st century in unraveling the
human genome offers for the first time the realization that significant
genetic screening, individualized pharmacotherapy, and genetic
manipulation will be a part of routine pediatric treatment and preven-
Northern Africa and Western Asia tion practices in the future. The prevention implications of the genome
3.3 project give rise to the possibility of reducing costs for the care of illness
1.9 but also increase concerns about privacy issues (see Chapter 3).
Although local famines and disasters, and regional and national
Latin America and the Caribbean
wars have periodically disrupted the general trend for global improve-
3.3
ment in child health indices, it was not until the advent of the AIDS
1.6
epidemic in the later 20th century that the first substantial global
Southern Asia erosion of progress in child health outcomes occurred. This erosion
2.3 resulted in ever-widening gaps between childhood health indices in
1.5 sub-Saharan Africa compared to the rest of the world. From 1990 to
Eastern Asia (excluding China) and South-Eastern Asia 2002, life expectancy in sub-Saharan Africa decreased from 50 yr to
2.1 46 yr. However, as of 2008, it had returned to 52 yr and in 2012 was
1.3 56 yr. Wide distribution of effective antiretroviral therapy (Fig. 1-4),
aggressive HIV prevention education, and increased access to antitu-
Sub-Saharan Africa bercular drugs have been important in these successes, but continued
2.0 successes will require sustained international support. Despite this
1.4 positive news, children with HIV remain the least-likely group to
Developing regions receive antiretroviral treatment. Despite these gains, diseases once con-
2.7 fined to limited geographic niches, including West Nile virus, and
1.5 diseases previously uncommon among humans, such as the avian flu
virus, increased awareness of the interconnectedness of health around
0 1 2 3 4 the world and the impact of global warming. Formerly perceived as a
Higher Equal Higher mortality among children of less problem of industrialized nations, motor vehicle crashes are now rec-
mortality among educated mothers ognized as a major cause of mortality in developing countries.
children of
educated mothers MORBIDITIES AMONG CHILDREN
Adequately addressing special healthcare needs is important in all
Children of mothers with no education compared to children of
countries, both to minimize loss of life and to maximize the potential
mothers with secondary or higher education
of each individual.
Children of mothers with no education compared to children of In the United States, ≈70% of all pediatric hospital bed days are for
mothers with primary education
chronic illnesses; 80% of pediatric health expenditures are for 20% of
Note: Analysis is based on 78 developing countries with data on under- children. Approximately 14% of U.S. children have special healthcare
five mortality rates by mother’s education, accounting for 75 needs, ranging from 10% to 19.8% across the 50 states and the District
percent of total births in developing countries in 2010. of Columbia. One in 5 households with children had ≥1 children with
Figure 1-3 Ratio of under-5 mortality rate of children of mothers with special healthcare needs (see Chapter 42). Significantly, more poor
no education compared to the rate of children of mothers with higher children and minority children have special healthcare needs.
education. (From Millennium Development Goals Report, 2012. New Although there are numerous chronic conditions and the prevalence
York, 2012, United Nations, p. 28.) of these disorders vary by population, 2 of these morbidities—asthma

7 Chronic cognitive morbidities represent another substantial
6 attention-deficit/hyperactivity disorder has been identified in 5-12%
5 United States, New Zealand, Australia, Spain, Italy, Colombia, and
Number (in millions)
4 screening approaches or tools may account for some of the differences
3 environmental interactions may also play a role. Despite variations in
2
1 for attention-deficit/hyperactivity disorder are estimated to exceed $4
0 tion, these children are unlikely to fulfill their academic potential (see
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
Number of people receiving antiretroviral therapy
Number of deaths from AIDS-related causes
Figure 1-4 Number of persons receiving antiretroviral therapy and
deaths caused by HIV over time. (From Millennium Development Goals
Report, 2012. New York, 2012, United Nations, p. 41.)
and nutrition disorders—have an increasing presence worldwide and
are associated with substantial health consequences and costs.
More than 80% of asthma-related deaths occur among children
living in developing countries. The Centers for Disease Control and
Prevention estimated that 10% of U.S. children have asthma, with
particularly high rates among Puerto Rican and black children.
Between 2001 and 2009, the prevalence of asthma increased by 50%
among black children. The International Study of Asthma and Aller-
gies in Childhood has presented evidence for a substantial global
burden of childhood asthma, although rates vary substantially between
and within countries. The highest annual prevalence rates are in the
United Kingdom, Australia, New Zealand, and Ireland, with the lowest
rates in Eastern European countries, Indonesia, China, Taiwan, India,
and Ethiopia (see Chapter 144).
Chronic disorders of nutrition occur in a variety of forms. Long
recognized as a major threat to child welfare, malnutrition (undernu-
trition) has been steadily decreasing over the past decades. Children
in industrialized countries have greatly benefitted from a wide range
of supplemental feeding programs (see Chapters 45 and 46); malnutri-
tion in such nations is generally a result of selected deficiencies rather
than overall undernutrition. An estimated 1% of children in the United
States have some form of malnutrition. Moderate and severe malnutri-
tion continue to impact children in developing nations. Although great
progress has been made in this regard over the past several decades,
children in the poorest nations and children whose families are in the
lower economic quintile in a broader range of countries continue to
struggle. In the period 2011–2013, 14% of children younger than age
5 yr in developing countries and 25% of those in the least-developed
countries suffer from moderate/severe malnutrition; South Asia and
West/Central Africa suffer from the highest rates of moderate/severe
malnutrition at 42% and 23%, respectively. Rates of stunting (>2 SD
below median height for age) are higher, at 29% and 41%, for children
in developing and the least-developed countries, respectively (see
Chapter 46).
The global epidemic of overweight/obesity is also significant. In the
United States, 30% of children and adolescents are overweight or obese,
representing a 3-fold increase over the past 30 yr. Rates of obesity for
boys whose parents did not graduate from high school are 3-fold
higher than those whose parents received at least a bachelor’s degree;
for girls, the difference is 2-fold. Similar rates have been reported from
Australia and multiple countries in Europe, Egypt, Chile, Peru, and
Mexico (see Chapter 47). The WHO estimates that globally 42 million
children younger than the age of 5 yr are overweight; ~35 million of
these live in developing countries.
Chapter 1 ◆ Overview of Pediatrics 5
problem. Although different diagnostic criteria have been applied,
of children in countries across the globe, with a worldwide estimated
prevalence of 5.29%. Rates exceeding 10% have been reported in the
Great Britain. Variations in cultural tolerance and/or differences in
in prevalence of the disorder by country, but genetic and gene–
rate, the condition is universal. Beyond the personal and familial
stress caused by the disorder, costs to the educational systems are
considerable. In countries where they are available, drug costs are
considerable; in the United States, annual costs for drug treatments
billion. In developing countries without resources for special educa-
Chapter 33).
Mental retardation affects ≈1-3% of children in the United States,
with ~80% of these children having mild retardation. Rates are several
fold higher among very-low birthweight infants. In the United States,
there is substantial variation in rates of mild retardation by socioeco-
nomic status (9-fold higher in the lowest compared to the highest
socioeconomic stratum), but relatively equivalent rates of severe retar-
dation. A similar income-related distribution is found in other coun-
tries, including some of the most impoverished countries, such as
Bangladesh. Lower overall rates have been reported in some countries,
including countries ranging from Saudi Arabia to Sweden to China;
the difference is primarily in the prevalence of mild retardation (see
Chapter 36).
Posttraumatic stress disorder (PTSD) in children remains under-
recognized. PTSD can follow violent attacks and witnessed violence,
sexual abuse, natural disasters, motor vehicle accidents, kidnapping,
and domestic violence. Female gender, prior exposure to violence,
other psychologic disturbances, and low social support are also associ-
ated with its appearance after an exposure. The prevalence of child-
hood PTSD varies considerably around the globe, but in children with
substantial exposure to violence, the rates appear to be very high. After
the attacks on the World Trade Center towers and the Pentagon in
2001, 33% of U.S. children had experienced 1 or more symptoms of
PTSD. The prevalence of PTSD among children and adolescents
exposed to the tsunami of 2004 were 57%, 46%, 31%, 10%, and 7%
6 wk, 6 mo, 1 year, 18 mo, and 2 yr post exposure, respectively. Chil-
dren hit by the waves had significantly higher rates of PTSD.
SITUATIONAL SPECIAL-RISK POPULATIONS
Children at situational special risk have had their futures compromised
by actions or policies arising from their families, schools, communities,
nations, or the international community. These problems have several
causes, whether the end result is homeless children, runaway children,
children in foster care, or children in other disadvantaged groups.
Children in Urban Settings
Over half of the world’s population is urban dwellers. Although urban
settings historically have offered educational, medical, recreational,
and employment opportunities, an increasing number of urban dwell-
ers are living in marginal communities with a growing gap in access to
clean water, adequate sanitation or dependable electricity as the urban
population rapidly increases (Fig. 1-5). As has been seen in Port-au-
Prince, Haiti, after the devastating earthquake of 2010, national disas-
ters exact an especially high toll on children and families living in
makeshift homes on lands that are not intended for housing.
Children in Poverty
Family income is central to the health and well-being of children.
Children living in poor families, especially those located in poor com-
munities, are much more likely than children living in upper- or
middle-class families to experience material deprivation and poor
health, die during childhood, score lower on standardized tests, be
6 Part I ◆ The Field of Pediatrics
723
Rural 450
370
1,052
Urban 813
1,089
0 200 400 600 800 1,000 1,200
Population (millions)
Population gaining access to improved drinking water
Population gaining access to improved sanitation
Population growth
Source: WHO/UNICEF Joint Monitoring Programme, 2010.
Figure 1-5 In urban areas, access to improved water and sanitation
is not keeping pace with population growth. (From UNICEF, The state
of the world’s children, 2012: children in an urban world, New York,
2012, United Nations, p. 5.)
retained in a grade or drop out of school, have out-of-wedlock births,
experience violent crime, end up as poor adults, and suffer other unde-
sirable outcomes. As of 2010, worldwide, 22% of the population lives
below the international poverty line of U.S. $1.25 per capita per day;
47% of sub-Saharan and 50% of the least-developed nations live below
this amount. Poverty rates are higher for children than adults and are
highest for infants and toddlers. Higher in general in developing coun-
tries, within each country, the rate of infant mortality among the
poorest quintile of the population is about twice that of the wealthiest
quintile (see Fig. 1-2).
In the United States, from 1990 to 2000, the percentage of children
<18 yr living below the poverty line had decreased from 21% to 16%.
In 2010, 2 yr after the start of the recession, the rate had risen to 22%.
Black and Hispanic children consistently have had higher poverty rates
than Asian and white children. In 2010, 39% of black children and 35%
of Hispanic children lived in poverty, compared to 14% of Asian chil-
dren and 12% of white children. Sixty-six percent of black and His-
panic children compared to only 33% of Asian and 29% of white
children lived below 200% of the poverty level. Children who are poor
have higher-than-average rates of death and illness from almost all
causes (exceptions being suicide and motor vehicle crashes, which are
most common among white, nonpoor children). Many factors associ-
ated with poverty are responsible for these illnesses: crowding, poor
hygiene and healthcare, poor diet, environmental pollution, poor edu-
cation, and stress.
Poverty and economic loss diminish the capacity of parents to be
supportive, consistent, and involved with their children. Clinicians at
all times, but especially in the context of a national or global recession,
need to be especially alert to the development and behavior of children
whose parents have lost their jobs or who live in permanent poverty.
Fathers who become unemployed frequently develop psychosomatic
symptoms, and their children often develop similar symptoms. Young
children who grew up in the Great Depression in the United States and
whose parents were subject to acute poverty suffered more than older
children, especially if the older ones were able to take on responsibili-
ties for helping the family economically. Such responsibilities during
adolescence seem to give purpose and direction to an adolescent’s life.
The younger children, faced with parental depression and unable to do
anything to help, suffered a higher frequency of illness and a dimin-
ished capacity to lead productive lives even as adults.
The pediatric team should ask parents about their economic
resources, adverse changes in their financial situation, and the family’s
attempts to cope. Encouraging concrete methods of coping, suggesting
ways to reduce stressful social circumstances while increasing social
networks that are supportive, and referring patients and their families
to appropriate welfare, job training, and family agencies can signifi-
cantly improve the health and functioning of children at risk when
their families live in poverty. In many cases, special services, especially
social services, need to be added to the traditional medical services;
outreach is required to find and encourage parents to use health ser-
vices and bring their children into the healthcare system. Pediatricians
also have the responsibility to contribute to, and advocate for, safety
net services for impoverished children within and outside the bound-
aries of their own country. An increasing number of programs are
available to help children of greatest need worldwide, such as Project
Smile, CARE, Project Hope, and Doctors Without Borders.
Children of Immigrants and Racial Minority
Groups Including U.S. Native Americans
Immigrants comprise >15% of the population in >50 countries, includ-
ing many Western European countries. Thirteen percent of the U.S.
population is foreign-born; 24% of all children in the United States <17
yrs have immigrant parents. The United States is experiencing a wave
of immigration larger than that occurring in the early 20th century.
Until the mid-20th century, emigrants to the United States were pri-
marily white and from Europe. Such individuals now represent only
approximately 10% of immigrants; the remainder are overwhelmingly
of color and from throughout the world, including 29% from Mexico,
5% from China, and 4% each from India and the Philippines. Although
immigrants in the United States have faced discrimination and oppres-
sion throughout history, the potential for such discrimination is com-
pounded by the racial differences represented in the current immigrant
pool. In the United States, about 240,000 children legally immigrate
each year, and, through 2010, an estimated 50,000/yr entered the
country illegally. In recent years the number of children from Latin
American countries entering illegally has greatly increased, with esti-
mates of more than 90,000 such children entering in 2014 alone. An
estimated 5.5 million children have at least 1 illegal immigrant parent;
this number doubled from 2000 to 2010.
The immigrant population constitutes a substantial proportion of
the low-wage labor market. Immigrants represent 16% of all U.S.
workers but 20% of low-wage workers. Immigrants are twice as likely
as U.S.–born citizens to earn less than minimum wage. The poverty
rate of children in immigrant families is 50% greater than in U.S.–born
families; over the past decade children with 2 immigrant parents con-
sistently have a 15% greater likelihood of living below the poverty line
than children in nonimmigrant families. Contributing to the lack of
access to higher salaried jobs is the lack of proficiency in English (≈52%
of immigrants) and the lack of education (40% have not completed
high school). Immigrants account for 29% of the uninsured in the
United States.
Families of different origins obviously bring different health prob-
lems and different cultural backgrounds, which influence health prac-
tices and use of medical care. To provide appropriate services, clinicians
need to understand these influences (see Chapter 4). The high preva-
lence of hepatitis among women from Southeast Asia makes use of
hepatitis B vaccine essential for their newborns. Children from South-
east Asia and South America have growth patterns that are generally
below the norms established for children of Western European origin,
as well as high rates of hepatitis, parasitic diseases, and nutritional
deficiencies and high degrees of psychosocial stress. Foreign-born
children may surpass American-born children in some health out-
comes, but their health deteriorates as they become acculturated (see
Chapter 4).
Refugee children who escape from war or political violence and
whose families have been subjected to extreme stress represent a subset
of immigrant children who have faced severe trauma. These children
have a particularly high incidence of mental and behavioral problems
(see Chapter 39). Armed conflicts in 2011 resulted in an especially high
(4 million) number of refugees worldwide.
Linguistically isolated households, in which no one older than
14 yr of age speaks English, often present significant obstacles to pro-
viding quality healthcare to children because of difficulties in under-
standing and communicating basic concerns and instructions, avoiding
 Chapter 1 ◆ Overview of Pediatrics 7

compromising privacy and confidentiality interests, and obtaining

informed consent (see Chapter 4). Table 1-3 Deaths Rates for All Causes Among Children
The United States is home to multiple minority populations, includ- and Young Adults According to Sex, Race,
ing the 2 largest groups, Latinos and African-Americans. The nonwhite Hispanic Origin, and Age: 2010
minority groups will constitute >50% of the U.S. population by 2050. Deaths Per 100,000 Resident Population
Nonwhite children in the United States disproportionately experience
adverse child health outcomes (Tables 1-3 and 1-4). Infants that are UNDER 1 yr 1-4 yr 5-14 yr 15-24 yr
born to African-American mothers experience low birthweight and All persons 623.4 26.5 12.9 67.7
infant mortality rates twice those with white mothers (see Chapter 93).
Rates of these 2 adverse health outcomes are also substantially higher Male 680.2 29.6 14.6 97.6
among some groups of Hispanic infants and children, the rates are Female 564.0 23.3 11.1 36.4
particularly high among those of Puerto Rican descent (≈1.5 times the MALES
rates for white infants). In 2010, the overall infant mortality rate was White 584.3 27.4 13.8 91.8
6.4 per 1,000 live births, whereas that for non-Hispanic African- Black male 1206.5 42.9 19.6 142.8
America infants was 11.7; for Native Americans, 8.3; and Puerto (African-American)
Ricans, 7.1. Mexicans, Asians, Pacific Islanders, Central and South American Indian or 542.5 34.3 18.1 116.4
Americans, and Cubans were below the national average. Latino, Alaska Native
Native American, and African-American children are substantially Asian or Pacific 434.4 19.3 8.4 43.0
more likely to live in poverty than are white children. Islander
There are approximately 5.1 million Native Americans (including Hispanic or Latino 556.8 25.0 11.4 79.4
White not Hispanic 594.4 29.3 15.0 100.8
those with mixed races/ethnicities) and 566 federally recognized tribes.
or Latino
The Native American population increased by 26% from 2000 to 2010
compared to a national increase of only 9.7%. Approximately 60% of FEMALES
Native Americans live in urban areas, not on or near native lands. Like White 575.9 27.5 14.3 93.4
their minority immigrant counterparts, they have faced social and Black (African- 488.0 21.6 10.6 36.2
economic discrimination. The unemployment and poverty levels of American)
American Indian or 366.4 24.4 10.5 43.6
Native Americans are, respectively, 3-fold and 4-fold that of the white Alaska Native
population, and far fewer Native Americans graduate from high school Asian or Pacific 341.8 16.3 7.9 17.0
or go to college. The rate of low birthweight among Native Americans Islander
is more than the white rate but less than the black rate. The neonatal Hispanic or Latino 462.9 20.2 8.9 26.3
and the postneonatal mortality rates are higher for Native Americans White not Hispanic 480.4 21.8 10.9 38.4
living in urban areas than for urban white Americans. Deaths in the or Latino
first year of life from sudden infant death syndrome, pneumonia, and Adapted from National Center for Health Statistics: Health, United States, 2013:
influenza are higher than the average in the United States, whereas with special feature on prescription drugs, Hyattsville, MD, 2014, Department of
deaths as a result of congenital anomalies, respiratory distress syn- Health and Human Services, Table 25, pp. 103–106.
drome, and disorders relating to short gestation and low birthweight
are similar.
Unintended injury deaths among Native Americans occur at twice
the rate for other U.S. populations; deaths caused by malignant

Table 1-4 Infant, Neonatal, and Postnatal Deaths and Mortality Rates by Specified Race or Origin of Mother: United
States, 2009 and 2010
Mortality Rate Per 1,000 Live Births
RACE OF MOTHER YEAR(S) INFANT NEONATAL POSTNATAL
All races 2007 6.4 4.2 2.2
2008 6.1 4.0 2.1
White 2007 5.3 3.5 1.9
2008 5.2 3.5 1.8
Black or African American 2007 12.1 8.0 4.2
2008 11.2 7.3 3.9
American Indian or Alaska Native 2007 8.3 4.3 4.0
Asian or Pacific Islander 2007 4.3 3.0 1.3
Hispanic or Latino 2007 5.3 3.6 1.7
Mexican 2007 5.1 3.5 1.6
Puerto Rican 2007 7.1 4.8 2.3
Cuban 2007 3.8 2.9 2.1*
Central and South American 2007 4.4 3.0 1.4
Other and unknown 2007 6.1 4.0 2.1
Hispanic or Latino
Not Hispanic or Latino
White 2007 5.2 3.4 1.8
Black or African American 2007 11.5 7.5 4.0
Adapted from National Center for Health Statistics: Health, United States, 2013: with special feature on prescription drugs, Hyattsville, MD, 2014, Department of
Health and Human Services, Tables 11, p. 98, and 17, p. 71.
*2009.
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myself continually for my disobedience. I never disobeyed him
before, and I seem to see his eyes full of reproach fixed upon me,
and to hear his voice—Oh, Arthur! Arthur!”
“Let me see the letter, darling.”
Neva extricated it from the folds of her dress, and gave it to him.
They halted while he read it. A look of surprise, wonder and
incredulity mantled Lord Towyn’s face as he read. It was followed by
a sternness that well became his fair and haughty face.
“I pronounce the letter a forgery!” he declared. “May I keep it, Neva,
for the present? I desire to show it to Mr. Atkins, who shall give us
his opinion on the handwriting.”
“Yes; keep it,” assented Neva.
Lord Towyn carefully put it in his pocket.
“I pronounce the letter a forgery,” he repeated sternly. “How did it
come to you, darling?”
“Lady Wynde gave it to me on my return from France. Papa desired
her to retain it for a year. Who would forge such a letter, Arthur?”
“I don’t know. I am puzzled. One cannot suspect Lady Wynde, and
yet—and yet—I don’t know what to think, Neva. I don’t believe Sir
Harold ever saw Rufus Black.”
“Rufus says he never saw papa, or that he never spoke to him,” said
Neva. “And that remark made me doubt the letter. But Rufus never
forged it, Arthur. Rufus is a kind-hearted, but weak-willed boy—he is
no more. If he had more ‘backbone’ in his character, he would be
even noble. I like him, Arthur, and I know he never wrote that letter.
Lady Wynde did not. She is too good for that. It might have been
written by Craven Black. I do not like him, and think him quite
capable of the forgery, only so many of the words are papa’s own
that it seems wicked to doubt its authenticity.”
“I will prove it a forgery!” cried the young earl. “Sir Harold was
incapable of binding your fate in this manner to a man you never saw
before it was written. There is some foul conspiracy against you,
Neva, but we have outwitted your enemies. I am impatient to have
you under my own guardianship. The possibility that you have
enemies makes me afraid to trust you from me. Give up this visit to
Wynde Heights, darling.”
“It is too late, Arthur. We shall stay there but a fortnight, and I have
promised to go. Papa bade me love his wife and obey her, and
though she no longer bears his name, and I no longer owe her
obedience, yet I have given my word to go up to Yorkshire with her,
and must keep my promise.”
“But when you return, Neva, you will marry me? Do not condemn me
to a long probation. Let us be married quietly some morning at
Wyndham church, after due intimation to our friends. Shall it not be
so?”
Neva yielded a shy assent.
“We will be married a month hence, Neva?” whispered the ardent
young lover.
“Two months,” said Neva, smiling. “I must not be too lightly won,
Lord Towyn. And, besides, I must have the orthodox trousseau. I will
tell Mrs. Black of our engagement when I am with her at Wynde
Heights. Rufus is not going with us, nor is Artress.”
They had threaded the wood and come out upon the highway long
since while they were talking, and were now within sight of
Hawkhurst. Rufus Black was riding out of the great gates, on his way
to meet Neva. The tete-a-tete of the young pair was over for the
morning, and recognizing the fact, and not wishing to proclaim his
happy secret to his defeated rival, Lord Towyn made his adieus to
Neva, begging her to write him daily from Yorkshire, which she
promised to do, and, then raising his hat to Rufus Black, the young
earl spurred his horse and rode swiftly on toward Wyndham.
Neva returned home with Rufus.
On Monday morning, Mr. and Mrs. Craven Black, accompanied by
Miss Wynde, departed for Wynde Heights.
On Wednesday, Lord Towyn looked for a letter from his young
betrothed. None came. Thursday, Friday and Saturday went by, and
still there came no letter from Neva, announcing her safe arrival in
Yorkshire.
The young earl wrote every day, his uneasiness increasing as the
time passed. He communicated his alarm to Sir John Freise and Mr.
Atkins, and they telegraphed to the clergyman of the little town in
whose vicinity Wynde Heights was situated, begging him to call and
see if Miss Wynde was in good health.
The answer to this dispatch came promptly, and also by telegraph. It
was to this effect:
“Sir John Freise and Mr. Atkins: Wynde Heights is
untenanted, save by the housekeeper. Miss Wynde has
not been here, nor have Mr. and Mrs. Black.”
On receipt of this astounding message, the young earl posted up to
town, as did Sir John Freise and Mr. Atkins. They searched for the
missing heiress and her guardians, but their search was futile. Not a
trace of her could be found. She had come up to London with her
enemies, but no further clue to her could be found. She had
completely disappeared, and her fate was shrouded in dark and
horrible mystery!
 CHAPTER II.
THE PUZZLE OF NEVA’S WHEREABOUTS.

On going up to town with Sir John Freise and Mr. Atkins to engage in
the search for Neva Wynde, who had so strangely and mysteriously
disappeared, Lord Towyn had left orders with the steward of his
marine villa to forward to him in London without delay any and all
letters that might arrive to the address of the young earl. And so,
while he prosecuted his researches with desperate energy, Lord
Towyn half expected by every post some news from his young
betrothed.
The three guardians of Neva’s estate were sadly puzzled and
thoroughly alarmed, but for Neva’s own sake they kept the mystery
to themselves. Mr. Atkins urged that no detectives be taken into their
confidence, and that no newspapers be permitted to publish the
strange story.
“We shall do as well as any detectives,” said the attorney, “and if
there is any game afoot, we will not set the villains who are at work
in it upon their guard.”
“Villains?” echoed Sir John Freise disapprovingly. “The thing is
mysterious, Mr. Atkins, but it is susceptible of explanation. Had it not
been for Miss Wynde’s promise to write daily to Lord Towyn, and her
failure to comply with that promise, we should have suspected no
harm. ‘Villains’ is a strong word to apply to Miss Wynde’s
companions. Miss Wynde may have fallen ill on the way to Wynde
Heights, or the plan of the tour may have been changed. In fact, one
of these alternatives doubtless contains the truth. But ‘villains,’ Mr.
Atkins—the word troubles me. To whom do you apply it? Certainly
not to the beautiful lady who was the wife of our friend Sir Harold
Wynde, and who was so loved and trusted by him that he constituted
her the sole personal guardian of his beloved daughter?”
“And who so appreciated her husband’s love and noble qualities,”
said Mr. Atkins dryly, “that in one year from his tragic death she was
receiving the loving attentions of a Craven Black, and in fifteen
months after Sir Harold’s death became the wife of a Craven Black!
Bah! I was never deceived in Lady Wynde, not even when Sir Harold
brought her home to Hawkhurst. She is a bold, designing,
unscrupulous creature, and it is as well that Sir Harold died before
she broke his heart.”
“Mr. Atkins, your harsh judgment amazes me—”
“I imagine, Sir John Freise,” said the attorney, “that in your secret
soul your opinion of Mrs. Craven Black is much higher than mine.
Have you been blind to the insatiable vanity, and the vulgarity and ill-
taste of the widow of Sir Harold Wynde, who, fifteen months after
losing the noblest husband the sun ever shone on, converts that
husband’s house into a ball-room, and sets his church bells ringing
and his tenantry dancing at her marriage with a gambler and
adventurer, unworthy even to breathe the same air with Sir Harold’s
pure young daughter? You look shocked, Sir John. If it were
necessary, I could give you my further opinion concerning Mrs.
Craven Black, but you are sufficiently shocked already.”
“You said, Mr. Atkins,” said Lord Towyn, “that you thought Mrs. Black
unscrupulous. I cannot believe her as base as you think, but I have a
question to submit to you and Sir John. When I asked Miss Wynde to
become my wife, she told me that it had been her father’s last wish
that she should marry Rufus Black—”
“Impossible!” cried Sir John and Mr. Atkins, in a breath.
“Miss Wynde showed me a letter purporting to have been written by
Sir Harold the night before his sudden death,” said Lord Towyn. “I
have the letter with me, and a study of it may throw light upon a
matter that certainly looks dark to me. I could almost make oath that
the deceased baronet never wrote this letter. It deceived Neva
completely, if it prove, as I have declared it, a forgery.”
He produced the letter, and gave it into the hands of Mr. Atkins. The
attorney read it aloud, weighing each phrase and turn of sentence.
“Sir Harold wrote it,” declared Sir John Freise, without hesitation. “I
have heard him express himself in those quaint, oddly turned
sentences a hundred times. Those pet names for his daughter, so
tender and poetical, were surely written by him. Miss Wynde
accepted the letter as genuine, and I do the same without question.”
“And you, my lord?” inquired Atkins.
“It seems to me a forgery,” said Lord Towyn. “Rufus Black confessed
to Neva that he had had no personal acquaintance with Sir Harold
Wynde.”
“That is odd,” declared Sir John, puzzled. “Perhaps Sir Harold was
not quite in his right mind when he wrote the letter. His presentiment
of approaching death may have unsettled his judgment; but that is
preposterous. I can’t explain the incongruities, but I persist in my
opinion that Sir Harold Wynde wrote the letter.”
“What is your opinion, Mr. Atkins?” demanded Lord Towyn.
“Where is Rufus Black?” asked the lawyer abruptly.
“Down at Hawkhurst. He remains there during the absence of the
bridal party,” answered the young earl in surprise.
“And Rufus Black has confessed to Miss Wynde that he was not
personally acquainted with Sir Harold Wynde?” mused the attorney.
“My opinion about young Black is, that he is a well-meaning but
weak-souled lad, just the person to be made a dupe or instrument in
the hands of more unscrupulous and daring souls. I don’t dislike the
boy. If he were his own master, or had a different father, he’d be a
decent fellow.”
“What do you think of his father, Atkins?” inquired Sir John.
“I think he’s a villain.”
“And what do you think of this letter, Atkins?” asked Lord Towyn.
“I think,” said Atkins quietly, “that it is a forgery. More, I know that it is
a forgery. Sir Harold Wynde was too tender a father to attempt to
control his daughter’s choice of a husband in a manner so singular.
The truth is, Craven Black has begun some sort of game against the
Wyndes, and if it don’t date further back than Sir Harold’s death, I
am mistaken. I see you look distressed, Sir John, so I will keep my
ideas to myself until I can prove their value. Lord Towyn, will you
allow me to retain this letter for the present, to study at my leisure?”
The young earl assented, and Atkins secured the letter on his
person.
“And now what are we to do?” asked Sir John.
“I shall take a turn up into Yorkshire, and have a look at Wynde
Heights for myself,” said Atkins. “You had better remain here, Sir
John, and not expose yourself to useless fatigue.”
“I shall go with you, Atkins,” declared the young earl.
Sir John Freise was anxious to accompany them, but he was
scarcely able to bear the fatigue of so hurried a journey, and
permitted himself to be overruled. He agreed to remain at their hotel,
the Langham, until the return of his friends from the north, and that
very evening Lord Towyn and Mr. Atkins departed for Yorkshire.
They arrived in due time at Wynde Heights, a lofty hill, crowned with
a beautiful, wide spreading villa, built after the Italian style, and
having long colonades. There were ample grounds attached to the
villa, a hundred acres or more in extent. Lord Towyn and Mr. Atkins
drove out to the place in a cab, and alighting at the carriage porch
rang loudly for admittance.
An old housekeeper, a Yorkshire woman, with a broad face and quiet
manners, and with but little of the usual Yorkshire burr in her speech,
opened the door cautiously after a long delay, and peeped out at
them with apparent timidity.
“How do you do, ma’am?” said the lawyer, raising his hat to her
respectfully. “We have called to see Miss Wynde and Mrs. Craven
Black.”
“The leddies are not here, sir,” answered the housekeeper.
“Not here!” exclaimed Atkins. “But Mrs. Black said they were coming
here.”
“Her leddyship wrote to me to have the house ready for her, after her
new marriage,” said the housekeeper, “and to engage servants,
which I did. And about two weeks ago I got a letter from her
leddyship, telling me to dismiss the servants and shut up the house,
as her leddyship had decided not to come to the Heights, and I
obeyed orders.”
“Will you show us that letter?” demanded the lawyer. “We are the
guardians of Miss Wynde’s estate, and find it necessary to see the
young lady at the earliest possible moment. We expected to find her
here, but the letter may afford us some clue to her whereabouts.
This gentleman is Lord Towyn, and I am William Atkins, the attorney
of the Wynde family.”
The housekeeper threw wide open the door of the house. Both
names were familiar to her, and she welcomed the visitors as those
having a right to the hospitalities of the place.
“Come in, my lord; come in, sir,” she exclaimed. “I will get the letter
for you.”
The visitors followed her into a cool, unused parlor, and seated
themselves, while the woman hurried away in quest of the letter of
which she had spoken.
“I had an idea that the Blacks might be stopping here secretly,” said
Atkins, in a low voice; “but I’ve changed my mind, my lord. They
have not been here. The housekeeper’s face is honesty itself. We’ll
have to look elsewhere. I’m sorry we’ve wasted time on the wrong
tack.”
The housekeeper reappeared with the letter. Lord Towyn and Mr.
Atkins read it. It had been written by Mrs. Craven Black, and was to
the effect that she had changed her mind, and that the bridal party
would not come north that season, and ordering the newly engaged
servants to be dismissed, and the house to be again closed.
Atkins sighed, as he restored the letter to the housekeeper.
“We are much obliged to you ma’am,” he said, “and now we must
hasten back to London. If you hear from your mistress, be kind
enough to drop me a line at my address. There’s my card. But it’s not
likely you will hear from Mrs. Black before we do.”
The visitors bade the housekeeper good morning, and hurried back
to the railway station in their cab, catching the down train, and
speeding on their way to London.
“I don’t believe our party is in England,” said Atkins musingly, as they
steamed swiftly down the line to the southward. “It would be like the
Blacks, if they had any game afoot, to make for the Continent. Our
next point is to make inquiries at the docks, or at the railway
stations.”
They arrived in London in the morning, and hastened to the
Langham hotel, where they had an interview with Sir John Freise,
who was looking worn and ill under all this suspense and anxiety.
The three gentlemen devoted the day to visiting the various railway
stations and offices of the Continental boats. They visited also the
foreign packet-boats lying in dock, and toward evening learned from
the steward of an Ostend boat, that a party such as was described,
consisting of two ladies and one gentleman, had crossed the
Channel to Ostend at about the time indicated by Atkins.
“Thank Heaven! We are on the track!” breathed Sir John.
“Atkins and I will start for Ostend by way of Dover this very night,”
said Lord Towyn, all ardor and impatience.
Atkins drew out a golden sovereign, which he held tantalizingly
before the eyes of the steward.
“Answer a few more questions,” said the attorney, “and this is yours,
my good fellow. Describe the gentleman who accompanied the two
ladies.”
The steward hesitated, eyeing the coin with greedy eyes.
“He was tall and fair, with mustaches,” he said slowly, as if fearing
the description would not suit his interlocutor, “and he was dressed in
black.”
“That would describe Craven Black well enough,” murmured Sir
John.
“And the ladies?” questioned Atkins. “How did they look?”
“One was some years older than the other, and was dark, with black
eyes. The young lady had lighter hair. They were going on to
Brussels, and I took it that the elder lady and gentleman were newly
married,” said the steward, “they were that sickish, begging your
pardon.”
“There’s no doubt we are on the right track,” cried Sir John, in a tone
of relief.
Atkins paid the steward the promised sovereign, and led the way
ashore and to the waiting cab.
“To the hotel,” he ordered.
The gentlemen entered the vehicle and hastened back to the
Langham. Atkins was very thoughtful and silent during the journey,
but as they drove up to the hotel he said:
“We are tired Lord Towyn, and must have rest. I propose that we
sleep here to-night, and go on to Dover and Ostend in the morning. I
know how anxious and impatient you are, but we must not overtask
our strength. You look quite worn out.”
“It is with anxiety then,” said the young earl. “I am eager to go on, Mr.
Atkins, but will wait till morning as you counsel.”
The three gentlemen ascended to their private parlor which they
shared in common. As they entered the room, a man who was
standing at one of the windows, looking out, turned and came
forward to meet them.
He was the steward of Lord Towyn’s marine place.
“You here, Sewel?” exclaimed the young earl. “Is anything the
matter?”
The steward, an elderly man, with a rugged countenance, as gnarled
as an old oak, yet full of kindly warmth, shook his head as he
answered:
“There’s nothing wrong, my lord; but you ordered any letters to be
sent to you, and knowing how anxious you were, I feared the letter
might miscarry, and here it is. I brought it myself.”
“A letter!” cried the three gentlemen in chorus, having no thought of
any letter save the one they so much desired.
“It’s in a lady’s hand, and that’s why I brought it,” said the steward.
He took out his pocket-book and drew from it a small square
envelope, daintily addressed and sealed.
Lord Towyn uttered a cry of joy, recognizing the handwriting at once.
“It is from Neva!” he ejaculated.
He hurried with it to a window, turning his back on his friends, and
tore open the envelope, disclosing a four-page letter, signed with the
name of Neva Wynde.
“Ah!” he cried aloud. “It is dated Brussels.”
“We were on the right track then,” said Atkins exultantly.
The young earl perused his letter with a glad heart.
It was very tender and very sweet, full of delicate allusions to their
betrothal, and was indeed such a letter as only a woman could write,
yet the young lover was not satisfied. The letter lacked the
straightforward simplicity that distinguished Neva, and it seemed to
Lord Towyn to lack also sincerity. It had been written from the head
rather than from the heart, and his first great joy and gladness gave
way to a sudden and terrible sense of disappointment.
The steward, seeing that he was not wanted, went quietly from the
room, intent upon securing his dinner.
Mr. Atkins and Sir John Freise approached our hero, and the baronet
laid a kindly hand upon the young earl’s shoulder.
“Forgive us for interrupting your happy reverie, Lord Towyn,” he said,
“but we are very anxious. Miss Wynde writes from Brussels, and in
good spirits? We have been troubling ourselves for nothing?”
The young earl did not look around, nor did he speak. He only
clutched the letter tighter in his fingers.
“We have got into a panic for nothing,” said Atkins, smiling. “We will
keep the joke to ourselves. I would not have Mr. Black curling his
cynical lips over our folly, not for worlds. No doubt Miss Wynde
satisfactorily explains her previous silence, my lord, and we are free
to return home again, wiser if not better men?”
The young earl turned to his companions now, and they started
when they saw how deadly pale he was, and what a look of terror
and anguish gleamed from his warm blue eyes.
“Miss Wynde is not ill?” cried Sir John.
Lord Towyn raised his arm, waving the letter in the air.
“This letter is in Neva’s handwriting, and signed with her name,” he
said, in a strained voice. “It purports to come from her, but, before
God, I believe it to be a forgery! My instinct tells me that Neva never
wrote it. We are upon the wrong track. Neva is not at Brussels.
Perhaps she is not out of England. She is in the hands of her
enemies, who have formed some foul conspiracy against her, and
we, O God! are powerless to save her!”
 CHAPTER III.
AN ADVERTISEMENT QUICKLY ANSWERED.

As the hour drew near for the arrival of the expected guest at Sandy
Lands, a suppressed excitement pervaded the pert little villa from
basement to attic. The servants had all received orders to wait upon
Mrs. Wroat with the utmost alacrity, and some notion of her wealth
and eccentricity had been conveyed to them, together with the idea
that Mr. and Mrs. Blight entertained “expectations” of inheriting the
old lady’s fortune at her death.
Mr. Blight had remained at home upon this day, in order that his
aunt-in-law might not conceive herself neglected by him. He was
dressed in his Sunday garments, and was practising a smile of
welcome, which had somewhat a sickly look, contrasted as it was
with his anxious eyes, and uneasy, apprehensive manner.
“Everything hangs upon this visit,” he muttered to himself, as he
stood at the parlor window, watching the road. “The old creature is a
bundle of whims and caprices, and if she should leave her money to
a charity we are undone. Our expenses are so heavy that I can no
longer meet them. The old woman must make her will in my favor!”
Mrs. Blight had attired herself in a tightly fitting gown of red silk,
through which her rotund figure threatened to burst at any moment,
and she wore a massive gold chain, a necklace, bracelets and
brooch, so that she might have personated at a fancy ball the
character of an animated jeweller’s shop.
“What have you got on all that jewelry for?” demanded Mr. Blight,
glancing at his wife, as she complacently surveyed the reflection of
her stout person and flushed face in the long mirror.
“Why?” said Mrs. Blight, with a degree of worldly wisdom for which
her husband, it is to be feared, had never given her credit, “there’s
nothing like making the old woman think we are prosperous. Money
brings money. If Aunt Wroat sees us haggling about the butcher’s
bills and the school bills, she may think her money is going into a
bottomless bucket. But if she sees us apparently rich, and without
money cares, she will be more anxious to leave her money to us.”
“That’s so,” said Mr. Blight. “I wish she’d come. Upon my soul, I do.
Why didn’t my uncle leave me his money, and give his wife an
annuity? In that case, I shouldn’t have cared what became of her,
and I certainly would not have been dancing attendance upon her.
All our care,” he added sourly, “and all our flattery will go for nothing
if the children are not kept out of the way. And there the young
savages come pellmell down the stairs.”
“The ‘young savages!’” moaned Mrs. Blight, in terrible reproach.
“Have you the soul of a father? Can you call your own offspring
savages, as if they were the children of a red Indian, or of cannibals?
I’ll send the poor dears back to the school-room. Between you and
your horrible old aunt, the poor darlings are in terror of their lives.”
Mrs. Blight hastened out into the hall, but it was now empty. The
young governess and the nurse had captured all of the refractory
brood save Leopold, and had conveyed them back to the school-
room. Leopold had made good his escape into the garden, and was
now careering about like a young colt, shouting at the top of his
voice.
Mrs. Blight, hearing the noise made by her offspring, was full of
terror lest her guest should arrive, and encounter the terrible infant at
the gate of Sandy Lands. She rang the bell violently, and ordered
Miss Bird to take charge of her pupil immediately. Lally descended to
the garden to obey this command, and at the very moment when he
chose to yield to her persuasions and be led away captive, a heavily
laden cab drove up to the garden door, and the garden bell was rung
violently.
The smart housemaid hastened to give admittance to the visitor, and
the youthful Leopold, greatly excited at the prospect of seeing Mrs.
Wroat, whom he detested, but cordially loved to annoy, struggled in
Lally’s grasp. The young girl drew her charge into the shadow of a
clump of trees, and stood there, panting and flushed, just as the
visitor’s luggage was brought in in advance of the visitor herself.
First came three large trunks, a bandbox in a green cotton bag, a
parrot in a cage, who croaked and chattered and muttered hoarse
threats, and a blue silk family umbrella.
And then followed the queerest old lady Lally had ever seen. She
leaned upon the arm of a tall, angular, hatchet-faced woman, her
maid and constant attendant, who spoke to her mistress with a
loving gentleness a mother might exhibit toward her child, but which
sounded strangely from her thin, compressed lips, and who guided
the faltering steps of her mistress with the tenderest care.
It was the old lady, however, upon whom Lally’s gaze was fixed with
strange intensity. She was thin and withered and bent, a mere wreck
of a woman who had been in her day handsome, graceful and
spirited. She was nearly eighty years of age, and her hands, incased
in black knitted mittens, through whose open meshes her bony
fingers showed, clasped a gold-headed staff, which partially
supported her, the maid giving her an arm.
The old lady wore an old-fashioned brocade gown, a big traveling
cloak, a white frilled cap, and a huge scuttle-shaped bonnet, such as
had been worn in her early prime. But her eyes were black and keen
and penetrating, full of sparkle and brightness; her hooked nose was
prominent like an eagle’s beak; and her mouth was curled habitually
in a strangely cynical smile or sneer.
The old lady gave a quizzical glance up at the doorway, in which
stood Mr. and Mrs. Blight with outstretched arms, and then looked
toward Lally. The young girl shrank back, and hurried in at the rear
porch and up stairs with her young charge, just as Mrs. Wroat came
in at the front door and was received by her connections with loud
exclamations of welcome.
The visitor was installed in her own apartments, and she did not
emerge from them for the remainder of the day. Mr. Blight went to his
office. A supernatural stillness reigned throughout the villa. Mrs.
Wroat chose to appear at dinner, which was served at Sandy Lands
at seven o’clock; and Mr. Blight was then at home to give her his arm
into the dining-room, and to pay her all necessary attentions.
She looked, as Mrs. Blight privately remarked to her husband, “like a
witch of Endor,” in her dinner costume of black velvet, with a scarlet
velvet circular cloak thrown about her thin bent figure, and with her
keen black eyes peering sharply out of her sallow face. She only
needed a scarlet hood over her gray, wild looking hair, to complete
her resemblance to one of the witches who are fabled to meet in
lonely wood at midnight, to stir devilish messes in boiling caldrons.
But then she wore a set of very fine diamonds, and even a “witch of
Endor,” with diamonds, would have been handsomely treated by
Mrs. Blight.
The old lady was not as courteous as a female Chesterfield. In fact
she snapped out spiteful remarks with the utmost unconsciousness
of the rising anger of host or hostess, taking a malicious pleasure in
stirring up their evil passions, knowing that they dared not give vent
to them. It may be that she comprehended their time-serving,
speculating natures, and realized that they paid court to her only for
her money.
“Miserable wine!” she commented, with a wry face, as she set down
her glass. “Gladstone, isn’t it, Charles? It comes at four and six the
dozen bottles, I believe. I never buy it myself. I prefer to take
wormwood and vitriol undiluted.”
The lawyer flushed. He prided himself on being a connoisseur of
wines, and having the choicest cellar in Canterbury.
“That’s real port, Aunt Wroat,” he exclaimed—“of the vintage of ’42.”
“Oh, they told you that, did they?” asked the old lady. “These cheap
wine dealers are up to all sorts of tricks. I am surprised that you
should have been taken in so, nephew Charles. At your time of life a
man should have some judgment of his own.”
Mr. Blight bit his lips furiously, and his wife fancied she heard the old
lady chuckle softly to herself, but a glance at her did not confirm the
impression.
Presently the old lady opened an attack upon the lawyer’s wife. She
looked at her though a quizzing-glass, and exclaimed suddenly, with
apparent astonishment:
“Laura, do you think it good taste to wear all that Brummagem? If I
could not get real gold, I wouldn’t put on servant’s ornaments; I
wouldn’t indeed.”
“But these are real gold, Aunt Wroat,” said Mrs. Blight, her voice
trembling with annoyance.
“Tut, tut,” said the old lady severely. “Don’t contradict me. I have
been used to good jewelry all my life, and ought to know it when I
see it. Good gold! Ha, ha! If you don’t know good gold, ask your
cook.”
Mrs. Blight nearly choked with rage, and sulked during the remainder
of the dinner, or until her husband threw her a warning glance that
reminded her that she could not afford to quarrel with their eccentric
relative.
Several times during the repast the host and hostess were stirred to
anger they dared not exhibit, and several times Mrs. Blight fancied
she heard the old lady chuckle to herself, but of this she could not be
quite sure. The Blights fawned upon their wealthy guest, swallowed
her insults, and smiled distractedly at her deadliest thrusts. But both
drew a sigh of relief when the old lady had been carried back into the
drawing-room.
“May be she’ll go to her room now?” whispered Mrs. Blight to her
husband, as the old lady fanned herself vigorously, and appeared
oblivious of their existence.
“No such good luck,” returned the lawyer ill-naturedly. “She ought to
be shut up in a lunatic asylum, the old nuisance. If it wasn’t for her
money, she might die in an alms-house before I’d give her shelter.”
The whisper was not low, but then Mrs. Wroat was supposed to be
“as deaf as a post,” and of course she could not hear a sound so
faint and indistinct. Mr. and Mrs. Blight had frequently vented their
opinions much more loudly before her. But there was an odd snap in
her eyes on this occasion, as they thus whispered to each other, and
again Mrs. Blight fancied she heard a malicious chuckle, but the old
lady fell to coughing in a frightful manner, and the lawyer’s wife had
no time for fancies, believing the old lady likely to die on the spot.
When the paroxysm was over, and Mrs. Wroat began to breathe
freely, Mrs. Blight said, not without nervousness:
“You have a terrible cold, Aunt Wroat. Don’t you do anything for it?”
“It’s a cold that’ll last me my days,” said Mrs. Wroat. “It’s
consumption.”
“Do you employ a doctor for it?” asked the lawyer.
“Death is the best doctor,” answered the old lady, with grim
facetiousness. “He’ll cure it for nothing. This is my last visit to you,
Charles. I sha’n’t last much longer.”
“Oh, I hope you will live twenty years yet, and visit us every year!”
cried Mrs. Blight. “Dear Aunt Wroat, we love to have you with us.”
“Yes, I know it,” said Mrs. Wroat, with another odd snap in her witch-
like eyes. “I know it, my dear. It’s time to settle my affairs. I am
thinking of making my will soon.”
The Blights tried to look unconcerned, but failed. Their curiosity and
anxiety displayed themselves in their features.
“Shall you leave your money to a charity, dear Aunt Wroat?” inquired
Mrs. Blight caressingly.
“No, no! I shall leave it to—But don’t ask me. You’ll know in good
time.”
The lawyer looked significantly at his wife.
“She means to leave it to us!” he whispered. “The old nuisance will
pay us for our trouble at last.”
It was singular that just then another fit of coughing attacked the old
lady. When it was over, she said sharply:
“I’ll go to my room. I want to be composed, or I sha’n’t sleep a wink
to-night. We’ll visit to-morrow, but I am tired after my journey. I
should like some one to play a little music for me in my room, but I
don’t want any sentimental songs from your girls, Laura.”
“The governess will sing and play for you, dear Aunt Wroat,” said
Mrs. Blight. “She has orders to obey you during your visit, and you
can command her at any or all hours.”
“Then send her to me in half an hour. Charles, you can carry me up
stairs.”
The lawyer obeyed the intimation, carrying the old lady up to her own
room and depositing her in her armchair. The maid was in
attendance, and the lawyer and his wife bade their guest an affecting
good-night, and retreated to the drawing-room to speculate upon
their prospects and the state of Mrs. Wroat’s health.
“Shut the door, Peters,” said the old lady. “And you might open the
windows and air the room after those people’s presence.”
Peters obeyed. She was wont to humor all the whims of her
mistress.
“Did you find them the same as usual, ma’am?” she asked.
“Just the same, Peters,” and the old lady sighed. “They call me ‘an
old cat’ and ‘a nuisance’ in whispers, and ‘dear Aunt Wroat’ out
aloud. Miserable hypocrites! I wanted to give them a last chance, but
they have ruined their prospects with me. Bah! A pair of fawning,
treacherous cats! They will never get a penny of my money beyond a
guinea to buy a mourning ring.”
“What shall you do, ma’am? Leave your money to a charity?”
“No, I won’t do that. I won’t have it scattered and doled out in
sixpennies and shillings, when the whole sum might go to enrich
some deserving person. I’ll leave you an annuity, Peters. You’re the
only true friend I have on earth.”
The woman caressed the withered hand of her old mistress with
genuine affection.
“Have you given up all hope of finding your own relatives, ma’am?”
she asked. “You tracked your niece until after her marriage with a
corn-chandler, and have discovered that she died, leaving one child,
a daughter, and that her husband died also. The girl may live,
ma’am. She’s the last of your blood, and surely it’s better to give to
your own kin than to undeserving connections or to strangers.”
“But I can’t find the girl,” sighed the old lady. “I’d adopt her and leave
her my money, if she was deserving of it; but I’ve set detectives to
look for her, and they have failed to discover anything except that her
moonstruck parents named her the ‘The Vailed Prophet,’ or ‘Lalla
Rookh,’ or some such nonsense. They did find out that she had been
educated like a lady—her mother was a lady—and that she had
taught music, or drawing, or something. But she may be dead by this
time.”
“We might advertise for her,” cried the maid all enthusiasm. “We
could say, if Miss So and So would call at such a place, she would
hear of something to her advantage. I do wish you would leave your
money to some nice young lady, instead of these people below. I’ll
write the advertisement immediately. What is the name of your great-
niece, Mrs. Wroat?”
“It’s Kubla Khan, or Lalla Rookh Bird,” answered the old lady. “There
was a crack in my niece’s brain, as was shown by her marriage with
a corn-chandler, and by the naming of her child. I wonder what kind
of a bird the corn-chandler was,” and Mrs. Wroat laughed queerly.
“He left his daughter not one penny to bless herself with. Write the
advertisement, Peters, at once. What geese we were not to have
thought of an advertisement before. If I can find and cage my Bird,
Peters, and it turns out a good and worthy Bird, I’ll leave her the
whole of my fifty thousand pounds, and you shall have an annuity,
Peters, and live with her and take care of her. She’s only a child—not
over seventeen.”
Peters brought out her mistress’ portable writing-desk, and sat down
before it to pen the required advertisement. Being unused to
composition, she spoiled a dozen sheets of paper before she
produced the following, which she read aloud to her mistress:
“If Miss Lalla Bird will apply to the undersigned she will
hear of something to her advantage. M. W., Mount street,
London, W.”
“That will do,” cried Mrs. Wroat delighted. “M. W.—Maria Wroat. Very
good. We’ll have it in all the London papers. Make a dozen copies of
it, and address them to a dozen different papers. You shall get the