Ectopic pregnancy a clinical casebook

Loomes, MDAssociate Professor of Pediatrics, Perelman School ofMedicine at the University of PennsylvaniaDivision of Gastroenterology, Hepatology and NutritionThe Children’s Hospital of

The 5-Minute Pediatric

Consult SIXTH EDITION

ASSOCIATE EDITORS

Louis M Bell, Jr., MD

Professor of Pediatrics at the University of Pennsylvania

Associate Chair of Clinical Activities

Chief, Division of General Pediatrics

The Department of Pediatrics

Children’s Hospital of Philadelphia

Perelman School of Medicine

Division of Pediatric Hematology

Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania

Kathleen M Loomes, MD

Associate Professor of Pediatrics, Perelman School of

Medicine at the University of Pennsylvania

Division of Gastroenterology, Hepatology and Nutrition

The Children’s Hospital of Philadelphia

ASSISTANT EDITOR Charles I Schwartz, MD

Clinical Assistant Professor of Pediatrics University of Pennsylvania School of Medicine Philadelphia, Pennsylvania

MANAGING EDITOR Cheryl Polchenko

General Pediatrics Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

The 5-Minute Pediatric

Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Acquisitions Editor: Rebecca Gaertner

Managing Editor: Nicole Walz

Project Manager: Bridgett Dougherty

Senior Manufacturing Manager: Benjamin Rivera

Marketing Manager: Kimberly Schonberger

Design Coordinator: Teresa Mallon

Production Services: Aptara, Inc.

5th Edition c 2008 by Lippincott Williams & Wilkins; 4th Edition c  2005 by Lippincott Williams & Wilkins

All rights reserved This book is protected by copyright No part of this book may be reproduced in any form

or by any means, including photocopying, or utilizing by any information storage and retrieval system withoutwritten permission from the copyright owner, except for brief quotations embodied in critical articles andreviews

The 5-Minute Logo is a registered trademark of Lippincott Williams & Wilkins This mark may not beused without written permission from the publisher

Printed in China

Library of Congress Cataloging-in-Publication Data

The 5-minute pediatric consult / [edited by] M William Schwartz; associate editors,

Louis M Bell, Jr [et al.]; assistant editor, Charles I Schwartz – 6th ed

p ; cm – (5-minute consult series)

Five-minute pediatric consult

Includes bibliographical references and index

ISBN 978-1-4511-1656-4 (hardback : alk paper)

or for any consequences from application of the information in this book and make no warranty, expressed

or implied, with respect to the currency, completeness, or accuracy of the contents of the publication.Application of this information in a particular situation remains the professional responsibility of thepractitioner

The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosageset forth in this text are in accordance with current recommendations and practice at the time of publication.However, in view of ongoing research, changes in government regulations, and the constant flow ofinformation relating to drug therapy and drug reactions, the reader is urged to check the package insert foreach drug for any change in indications and dosage and for added warnings and precautions This isparticularly important when the recommended agent is a new or infrequently employed drug

Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA)clearance for limited use in restricted research settings It is the responsibility of health care providers toascertain the FDA status of each drug or device planned for use in their clinical practice

The publishers have made every effort to trace copyright holders for borrowed material If they haveinadvertently overlooked any, they will be pleased to make the necessary arrangements at the first

WS: To Susan, David, Charlie, Brandie, Mitchell, Caroline, and Chloe LB: To my mom and dad, Deasue and Louis Thank you for all of the

intangibles

PB: For Nishan, at the beginning EC: In Memory of Dr Ed Baik Chung and Dr Okhyung Kang and

Dennis, Marissa and Emma Lee

DF: To Marisa, Elias, Henry, and Isabel KML: To my mother Joan

PM: To my family and patients MM: To my wonderful family Thanks for all your support RT: To Sarah, Meghan, Lauren, and my many teachers and mentors

T his sixth edition of The 5-Minute Pediatric Consult attests to

the continuing value to the readers of the content and

innova-tive format A sixth edition! Wow! I look back on the history of

this text and now website with pride and much pleasure When the

first edition was proposed in 1995, the new format of the 5-Minute

series intrigued me The innovative design, fitting well into the

evolv-ing computer technology, first Personal Digital Assistants and then

the internet, has led to wide acceptance of this presentation that

provides easy access to important information The popularity of The

5-Minute Pediatric Consult is a testimony to the excellent work of

the authors and editors who write the chapters, and to the editorial

and production staff who transform the pages into the final book

and website.

This edition contains many chapters rewritten by a group of new

authors as well as refinement of all chapters There are a number of

new topics written by child psychiatrists such as separation anxiety,

substance abuse, and obsessive compulsive disorders My thanks

to Pace Ducket for recruiting these authors We added new topics

such as narcolepsy, dental trauma, fragile X syndrome, thoracic

insufficiency syndrome, and vaccine reactions.

I have been fortunate to have a team of associate editors, many

have been on this project for all six editions, while others joined

us later but continued the high level of professionalism and

dedica-tion to this book I appreciate the efforts of Lou Bell, Peter Bingham,

Esther Chung, David Friedman, Kathy Loomes, Petar Mamula,

Maria Mascarenhas, and Ronn Tanel My gratitude to all of them

for their efforts to continue the reputation of high quality known in

The 5-Minute Pediatric Consult One of the principles for working

on this project is it should be fun I know it has been enjoyable for

me As the internet and notebooks become more popular, my old

fashioned bias for real books will continue despite the prediction

that books will be obsolete in the future I hope not.

Being involved in many ways with educating medical students

at Penn and residents at Children’s Hospital of Philadelphia, and

visiting many hospitals, I was able to see firsthand how this book was

helpful to trainees, primary care pediatricians, and nurses, and thus,

justifying the name of The 5-Minute Pediatric Consult The spread

of the book to other countries in many translations was gratifying

and exceeded my initial expectations.

not want to be remembered as the old man with a poor memory who stayed too long One day he got a tap on his shoulder; he knew what that meant Our memories of him remain positive On the other hand, our former chief of pediatrics would sleep through grand rounds and when prodded to answer a question, he began to talk about his favorite disease, even though it was not the topic of the session; so much for his reputation These contrasting obser- vations have helped form some of my professional philosophies I always made sure that I did not stay too long, mainly to allow for the next generation to have opportunities that I was fortunate to have

in my career Therefore, with this sixth edition, I am retiring from

editorship of The 5-Minute Pediatric Consult and look to the future

of the book under the new team.

Before I go, I do want to express my appreciation and special thanks to Cheryl Polchenko, managing editor and a good pal, who has held all the pieces together and assured the completion of these editions In every group there is a special person who quietly

stands out, Cheryl is that person Grazie mille! Likewise, that staff

at Wolters Kluwer Health (that was Lippincott that was Williams

& Wilkins) My friends and associates at Wolters Kluwer Health made working on this project a great pleasure Thanks to Sonya Seigafuse, Rebecca Gaertner, and Nicole Walz who worked on the sixth edition and to Tim Hiscock, Katie Millet, and Joyce Murphy from the past editions I appreciate them being so helpful Sandhya Joshi headed the production team that turned the manuscripts into

this book Molte grazie to all of them.

At this time of reflection, I also want to acknowledge people, most of whom are no longer with us but their influence on me remains First my parents who were book lovers and set a great ex- ample for the joys of reading and the value of education Then my teachers, mentors, and colleagues including Willis Hunt, an eccen- tric but lovable biology teacher, Isaac Starr, my research mentor who showed that one could be a first rate scientist as well a gentleman (I loved his advice that “all the easy things have been done already.”), Harold Farmer, a general internist who demonstrated an enthusiasm for teaching and for delving into medical history, and Francis Wood who set the example that excellent medical care has to be combined with compassionate doctor–patient communication My fond mem- ories of training at Children’s Hospital of Philadelphia include my

Akinyemi Ajayi, MD, FCCP, FAASM

Children’s Lung, Asthma and Sleep

Specialists and the Children’s Sleep

Laboratory

Orlando, Florida

Ali Al-Omari, MD

Pediatric Orthopaedic Fellow

Department of Orthopaedic Surgery

The Children’s Hospital of Philadelphia

Division of Endocrinology and Diabetes

The Children’s Hospital of Philadelphia

Professor of Clinical Pediatrics

The Perelman School of Medicine

UCSF Benioff Children’s Hospital San Francisco, California

Edward F Attiyeh, MD

Assistant Professor of Pediatrics Children’s Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

J Christopher Austin, MD, FAAP, FACS

Associate Professor Department of Urology Pediatric Urology Oregon Health and Science University Portland, Oregon

Oluwakemi B Badaki-Mukan, MD, CM

Instructor of Pediatrics Department of Pediatrics Pediatric Emergency Medicine Research Fellow

Department of Emergency Medicine

Department of Pediatrics The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Diane Barsky, MD

Attending Physician Division of Gastroenterology, Hepatology and Nutrition

Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Hamid Bassiri, MD, PhD

Clinical Associate and Attending Division of Infectious Diseases Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Suzanne E Beck, MD

Associate Professor of Clinical Pediatrics University of Pennsylvania School of Medicine

Miami, Florida

x r r r Contributing Authors

Anita Bhandari, MD

Assistant Professor of Pediatrics

Division of Pediatric Pulmonology

Connecticut Children’s Medical Center

Hartford, Connecticut

Sumit Bhargava, MD

Clinical Associate Professor

Department of Pediatrics

Stanford School of Medicine

Attending Pulmonologist and Sleep

Physician

Lucille Packard Childrens Hospital

Palo Alto, California

The Children’s Hospital of Philadelphia

Assistant Professor of Ophthalmology

The Perelman School of Medicine at the

University of Pennsylvania

Philadelphia, Pennsylvania

Mercedes M Blackstone, MD

Attending Physician

Pediatric Emergency Medicine

Children’s Hospital of Philadelphia

Assistant Professor of Clinical Pediatrics

Perelman School of Medicine at the

Christopher P Bonafide, MD, MSCE

Assistant Professor of Pediatrics

University of Pennsylvania

Division of General Pediatrics

The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania

James Boyd, MD

Assistant Professor of Neurology

University of Vermont College of Medicine

Burlington, Vermont

Laura K Brennan MD

Attending Physician

Division of General Pediatrics

The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania

Lee J Brooks, MD

Clinical Professor of Pediatrics University of Pennsylvania Attending Physician Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Jeffrey P Brosco, MD, PhD

Director Pediatrics Program Professor of Clinical Pediatrics Department of Pediatrics University of Miami Miller School of Medicine

Miami, Florida

Kurt Brown, MD

Senior Director Clinical Research Group Director Neuroscience Therapeutic Area AstraZeneca

Wilmington, Delaware

Valerie I Brown, MD, PhD

Assistant Professor Division of Pediatric Hematology/

Oncology Department of Pediatrics Vanderbilt Children’s Hospital Vanderbilt-Ingram Cancer Center Nashville, Tennessee

Fletcher Allen Health Care Burlington, Vermont

Genevieve L Buser, MD, MSHP

Pediatric Infectious Diseases Fellow Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Francesca Byrne, MD

Department of Pediatric Cardiology University of California, San Francisco San Francisco, California

Michael D Cabana, MD, MPH

Professor of Pediatrics Epidemiology & Biostatistics University of California, San Francisco Department of Pediatrics

San Francisco, California

Andrew C Calabria, MD

Attending Physician Division of Endocrinology and Diabetes The Children’s Hospital of Philadelphia Assistant Professor of Pediatrics Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania

Robert M Campbell, Jr, MD

Director The Center for Thoracic Insufficiency Syndrome

Pediatric Orthopaedist Division of Orthopaedic Surgery The Children’s Hospital of Philadelphia Professor of Orthopaedic Surgery The University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania

Douglas A Canning, MD

Director Division of Urology The Children’s Hospital of Philadelphia Professor of Urology in Surgery Perelman School of Medicine, University

of Pennsylvania Philadelphia, Pennsylvania

William B Carey, MD

Director of Behavioral Pediatrics Division of General Pediatrics The Children’s Hospital of Philadelphia Clinical Professor of Pediatrics University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania

Vanessa S Carlo, MD

Assistant Professor of Pediatrics Thomas Jefferson University Philadelphia, Pennsylvania

Michael C Carr, MD, PhD

Associate Director Pediatric Urology Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Leslie Castelo-Soccio, MD, PhD

Attending Physician, Pediatrics and Dermatology

Section of Dermatology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Contributing Authors r r r xi

Elizabeth Candell Chalom, MD

Assistant Professor of Pediatrics

University of Medicine and Dentistry

of New Jersey

Chief, Pediatric Rheumatology

Saint Barnabas Medical Center

Livingston, New Jersey

Candice Chen, MD, MPH

Assistant Research Professor

Department of Health Policy

School of Public Health and Health

Child Abuse and Neglect Prevention

The Children’s Hospital of Philadelphia

Jefferson Medical College

Thomas Jefferson University

Rosalyn D´ıaz Crescioni, MD

Department of Gastroenterology Puerto Rico Children’s Hospital Bayam ´on, Puerto Rico

Randy Q Cron, MD, PhD

Professor of Pediatrics & Medicine Director of Pediatric Rheumatology University of Alabama at Birmingham Birmingham, Alabama

Kristin E D’Aco, MD

Fellow Clinical and Biochemical Genetics Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

George A Datto, MD

Department of Pediatrics Nemours

A I duPont Hospital for Children Wilmington, Delaware

Richard S Davidson, MD

Professor of Orthopedic Surgery Department of Orthopedic Surgery Children’s Hospital of Philadelphia University of Pennsylvania School of Medicine

Dennis J Dlugos, MD

Director Pediatric Regional Epilepsy Program The Children’s Hospital of Philadelphia Associate Professor of Neurology and Pediatrics

Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

Chief of Orthopaedic Surgery The Children’s Hospital of Philadelphia Division of Orthopaedic Surgery Philadelphia, Pennsylvania

Monica Dowling, PhD

Assistant Professor Clinical Pediatrics Clinical Psychology

University of Miami Miller School of Medicine Mailman Center for Child Development Miami, Florida

Naomi Dreisinger, MD, MS, FAAP

Director Pediatric Emergency Department Beth Israel Medical Center Asst Professor

Pediatrics Albert Einstein College of Medicine New York City, New York

Nancy Drucker, MD

Pediatric Cardiology Fletcher Allen Health Care Associate Professor University of Vermont College of Medicine Burlington, Vermont

xii r r r Contributing Authors

Sadiqa Edmonds, MD

Fellow

Division of Pediatric Emergency Medicine

Children’s Hospital of Philadelphia

Director of Health Services Research for

Women and Children

Department of Medicine and Obstetrics

Physicians and Surgeons

Doernbecher Children’s Hospital

Oregon Health and Science University

Portland, Oregon

Stephen J Falchek, MD

Instructor

Departments of Pediatrics and Neurology

Thomas Jefferson University

Interim Division Chief

Division of Pediatric Neurology

A.I duPont Hospital for Children

The Children’s Hospital of Philadelphia

and University of Pennsylvania

Perelman School of Medicine

Philadelphia, Pennsylvania

Kristen A Feemster, MD, MPH, MSHP

Assistant Professor of Pediatrics

Perelman School of Medicine

University of Pennsylvania

Division of Infectious Diseases

The Children’s Hospital of Philadelphia

New York City, New York

Pearlman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania

Kristin N Fiorino, MD

Assistant Professor Department of Pediatrics Attending Physician Division of Gastroenterology, Hepatology, and Nutrition

The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Brian T Fisher, DO, MSCE, MPH

Assistant Professor of Pediatrics The Children’s Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

Michael J Fisher, MD

Associate Professor Division of Oncology Department of Pediatrics Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Jonathan Fleenor, MD, FACC, FAAP

Pediatric Cardiology Children’s Hospital of the King’s Daughters

Norfolk, Virginia

John M Flynn, MD

Professor of Orthopaedic Surgery The University of Pennsylvania School of Medicine

Associate Chief of Orthopaedics The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Matthew Isaac Fogg, MD

Allergy and Asthma Specialists, PC Attending Allergist

St Christopher’s Hospital for Children Clinical Assistant Professor of Pediatrics Drexel University College of Medicine Philadelphia, Pennsylvania

Brian John Forbes, MD, PhD

Associate Professor Ophthalmology & Pediatrics Perelman School of Medicine at the University of Pennsylvania Department of Ophthalmology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

James P Franciosi, MD, MS

Assistant Professor Department of Gastroenterology University of Cincinnati

Cincinnati Children’s Hospital Cincinnati, Ohio

David F Friedman, MD

Clinical Assistant Professor of Pediatrics

at the University of Pennsylvania Perelman School of Medicine Division of Pediatric Hematology Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Joshua R Friedman, MD, PhD

Assistant Professor Department of Pediatrics The Children’s Hospital of Philadelphia The Perelman School of Medicine at the University of Pennsylvania

Philadelphia, Pennsylvania

Sarah M Frioux, MD

Major U.S Army Department of Pediatrics Tripler Army Medical Center Tripler AMC, Hawaii

Theodore J Ganley, MD

Director of Sports Medicine The Children’s Hospital of Philadelphia Associate Professor of Orthopaedic Surgery

The University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania

Ana Catarina Garnecho, MD

Developmental-Behavioral Pediatrics Neurodevelopmental Center Department of Pediatrics Memorial Hospital of Rhode Island Warren Alpert School Medical School of Brown University

Jackie P.-D Garrett, MD

Fellow Physician Division of Allergy and Immunology Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Contributing Authors r r r xiii

Jeffrey S Gerber, MD, PhD

Assistant Professor of Pediatrics

University of Pennsylvania School of

Medicine

Division of Infectious Diseases

The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania

Lynette A Gillis, MD

Associate Professor

Department of Pediatrics

Divisions of Pediatric Gastroenterology,

Hepatology, and Nutrition and Medical

Genetics

Vanderbilt University Medical Center

Nashville, Tennessee

Jenifer A Glatz, MD

Assistant Professor of Pediatrics

Pediatric Cardiology Children’s Hospital at

Dartmouth

Manchester, New Hampshire

Samuel B Goldfarb, MD

Division of Pulmonary Medicine

The Children’s Hospital of

UMass Memorial Health Care/

Hahnemann Family Health Center

Levine Children’s Hospital at Carolinas Medical Center

Charlotte, North Carolina

Marc Gorelick, MD, MSCE

Sr Associate Dean for Clinical Affairs Professor of Pediatrics, and Chief of Pediatric Emergency Medicine Medical College of Wisconsin Jon E Vice Chair in Emergency Medicine Children’s Hospital of Wisconsin Milwaukee, Wisconsin

Neera Goyal, MD, MSc

Assistant Professor of Pediatrics Division of Neonatology and Pulmonary Biology

Division of Hospital Medicine Cincinnati Children’s Hospital Medical Center

Cincinnati, Ohio

William R Graessle, MD

Associate Professor of Pediatrics Cooper Medical School of Rowan University

Camden, New Jersey

Ernie Graham, MD

Department of Gyn/Ob Johns Hopkins University School of Medicine

Baltimore, Maryland

Rose C Graham, MD, MSCE

Adjunct Assistant Professor of Pediatrics University of North Carolina School of Medicine

Chapel Hill, North Carolina Attending Physician Pediatric Gastroenterology Mission Children’s Specialists Asheville, North Carolina

Andrew B Grossman, MD

Clinical Assistant Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Attending Physician Division of Gastroenterology, Hepatology, and Nutrition

The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Blaze Robert Gusic, MD, FAAP

Las Vegas, Nevada

Chad R Haldeman-Englert, MD

Assistant Professor Department of Pediatrics Wake Forest Baptist Medical Center Winston-Salem, North Carolina

J Nina Ham, MD

Assistant Professor of Pediatrics Pediatric Diabetes and Endocrinology Section

Baylor College of Medicine Houston, Texas

Brian D Hanna, MDCM, PhD

Director Section of Pulmonary Hypertension Division of Cardiology

The Children’s Hospital of Philadelphia Clinical Professor of Pediatrics Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania

Jessica K Hart, MD

Pediatric Hospitalist Department of General Pediatrics Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Sandra G Hassink, MD

Director Nemours Obesity Initiative

xiv r r r Contributing Authors

David Hehir, MD

Assistant Professor of Pediatrics

Divisions of Cardiology and Critical Care

Children’s Hospital of Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin

Eugene R Hershorin, MD

Associate Professor of Clinical Pediatrics

Chief – Division of General Pediatrics

Associate Chair – Department of

Department of Emergency Medicine

Albert Einstein College of Medicine

Bronx, New York;

Research Director

Department of Emergency Medicine

Beth Israel Medical Center

New York, New York

Director, Clinical Toxicology

Emergency Services Institute

Sheikh Khalifa Medical City

Abu Dhabi, United Arab Emirates

Jessica Hoseason, MD

Resident

Doernbecher Children’s Hospital

Oregon Health and Science University

Pediatric Emergency Medicine

Director of Medical Education – DCMC

Cynthia R Jacobstein, MD, MSCE

Assistant Professor of Clinical Pediatrics Department of Pediatrics

Division of Emergency Medicine Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Douglas Jacobstein, MD

Attending Physician Division of Pediatric Gastroenterology and Nutrition

Sinai Hospital of Baltimore Baltimore, Maryland

Irfan Jafree, MD

Electrophysiology Fellow Department of Neurology University of Vermont College of Medicine Burlington, Vermont

John Lynn Jefferies, MD, MPF, FACC, FAAP

Associate Professor Pediatric Cardiology Director

Advanced Heart Failure, Cardiomyopathy, and Ventricular Assist Device Programs Co-Director

Cardiovascular Genetics Associate Director Heart Institute Research Core Cincinnati Children’s Hospital Medical Center

University of Cincinnati Cincinnati, Ohio

Anne K Jensen, BA

Medical Student Division of Ophthalmology Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Payal S Kadia, MD

Fellow Pediatric Emergency Medicine Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Binita M Kamath, MBBChir, MRCP, MTR

Staff Physician Division of Gastroenterology, Hepatology and Nutrition

The Hospital for Sick Children Associate Scientist

Research Institute Assistant Professor University of Toronto Toronto, Canada

Robert D Karch, MD, MPH, FAAP

Director Pediatric Hospital Medicine Nemours Children’s Hospital Orlando, Florida

Andrea Kelly, MD, MSCE

Assistant Professor of Pediatrics Division of Endocrinology & Diabetes Children’s Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

Janice Anne Kelly, MD

Clinical Associate Professor of Pediatrics University of Pennsylvania

Division of Gastroenterology and Nutrition Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Judith Kelsen, MD

Assistant Professor of Pediatrics The Children’s Hospital of Philadelphia Division of Gastroenterology

Philadelphia, Pennsylvania

Shellie M Kendall, MD

Clinical Fellow Pediatric Cardiology University of California, San Francisco San Francisco, California

Melissa Kennedy, MD

Attending Physician Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Contributing Authors r r r xv

Hans B Kersten, MD

Associate Professor of Pediatrics

St Christopher’s Hospital for

Children

Drexel University College of Medicine

Philadelphia, Pennsylvania

Leslie Kersun, MD, MSCE

Inpatient Medical Director

Division of Oncology

The Children’s Hospital of

Philadelphia

Assistant Professor of Pediatrics

Perelman School of Medicine at the

University of Pennsylvania

Philadelphia, Pennsylvania

Jason Y Kim, MD, MSCE

Division of Infectious Diseases

The Children’s Hospital of

Pediatric Medical Student Education

Department of Community Pediatric

Health

Children’s National Medical Center

The George Washington University

Pediatric Sleep Medicine Training Program

Children’s Hospital Boston Boston, Massachusetts

Renee K Kottenhahn, MD, FAAP

Clinical Associate Professor of Pediatrics Jefferson Medical College of Thomas Jefferson University

Philadelphia, Pennsylvania Associate Director Pediatric Practice Program and Attending Physician

Department of Pediatrics Christiana Care Health Services Wilmington, Delaware

Wendy J Kowalski, MD

Attending Neonatologist Department of Neonatology Lehigh Valley Hospital Allentown, Pennsylvania

Matthew P Kronman, MD, MSCE

Assistant Professor, Division of Infectious Diseases

Department of Pediatrics University of Washington/Seattle Children’s Hospital

David R Langdon, MD

Clinical Director Division of Endocrinology Children’s Hospital of Philadelphia Clinical Associate Professor University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania

Judith B Larkin, MD, FAAP

Instructor in Pediatrics Nemours Pediatrics, Philadelphia Thomas Jefferson University Hospital Philadelphia, Pennsylvania

A I duPont Hospital for Children Wilmington, Delaware

Dale Young Lee, MD

Fellow Pediatric Gastroenterology, Hepatology, and Nutrition

Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Rebecca K Lehman, MD

Assistant Professor Department of Neurosciences Division of Pediatric Neurology Medical University of South Carolina Charleston, South Carolina

xvi r r r Contributing Authors

Daniel H Leung, MD

Assistant Professor of Pediatrics

Gastroenterology, Hepatology, and

Nutrition

Texas Children’s Hospital

Baylor College of Medicine

Division of Adolescent Medicine

St Christopher’s Hospital for

Clinical Professor of Pediatrics

University of California, San Francisco

San Francisco, California

Atlanta, Georgia

Kathleen M Loomes, MD

Associate Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Division of Gastroenterology, Hepatology and Nutrition

The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania

Alexander Lowenthal, MD

Senior Echocardiography Fellow Lucile Packard Children’s Hospital at Stanford

Palo Alto, California

Sheela N Magge, MD, MSCE

Assistant Professor of Pediatrics University of Pennsylvania Perelman School of Medicine

Division of Endocrinology and Diabetes

The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania

Shannon Manzi, PharmD

Team Leader, Emergency Services Department of Pharmacy

Children’s Hospital Boston Boston, Massachusetts

Petar Mamula, MD

Associate Professor of Pediatrics University of Pennsylvania Perelman School of Medicine

Division of Gastroenterology, Hepatology and Nutrition

The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania

Yang Mao-Draayer, MD, PhD

Associate Professor Department of Neurology University of Michigan Ann Arbor, Michigan

Bradley S Marino, MD, MPP, MSCE

Associate Professor of Pediatrics University of Cincinnati College of Medicine

Director Heart Institute Research Core Director

Heart Institute Neurodevelopmental Clinic

Attending Physician Cardiac Intensive Care Unit Divisions of Cardiology and Critical Care Medicine

Cincinnati Children’s Hospital Medical Center

Cincinnati, Ohio

Jennifer A Markowitz, MD

Department of Neurology Children’s Hospital of Boston Boston, Massachusetts

Jonathan Markowitz, MD, MSCE

Director Children’s Center for Digestive Health Greenville, South Carolina

Oscar Henry Mayer, MD

Division of Pulmonology The Children’s Hospital of Philadelphia

Assistant Professor of Clinical Pediatrics

Perelman School of Medicine of the University of Pennsylvania Philadelphia, Pennsylvania

Erin E McGintee, MD

Attending Physician Allergy and Immunology ENT and Allergy Associates, LLP East Hampton, New York

Contributing Authors r r r xvii

Susan McKamy, PharmD, BCPS

Assistant Clinical Professor

Department of Clinical Pharmacy

School of Pharmacy

University of California, San Francisco

San Francisco, California

Clinical Lead Pharmacist

Miller Children’s Hospital of Long Beach

Long Beach, California

Heather McKeag, MD

Assistant Professor of Pediatrics

Tufts University School of Medicine

Associate Professor of Pediatrics

University of California San Francisco

San Francisco, California

Devendra I Mehta, MBBS, MSc, MRCP

Assistant Professor Department of Pediatrics Thomas Jefferson University Pediatric Gastroenterologist Department of Pediatrics Nemours Children’s Clinic Orlando, Florida

Michelle E Melicosta, MD, FAAP

U.S Army Health Center Wiesbaden, Germany

Heather L Meluskey, BS, BSN, RN

Pulmonary Hypertension Nurse Coordinator

Department of Cardiology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Laura M Mercer-Rosa, MD, MSCE

Assistant Professor in Pediatrics Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania

Kevin E C Meyers, MBBCh

Associate Professor of Pediatrics Nephrology Division

Department of Pediatrics The Children’s Hospital of Philadelphia University of Pennsylvania

Philadelphia, Pennsylvania

Monte D Mills, MD

Director Division of Ophthalmology The Children’s Hospital of Philadelphia Associate Professor

Ophthalmology Perelman School of Medicine, University

of Pennsylvania Philadelphia, Pennsylvania

Jane E Minturn, MD, PhD

Division of Oncology The Children’s Hospital of Philadelphia Assistant Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

Rakesh D Mistry, MD, MS

Assistant Professor of Pediatrics University of Pennsylvania School of Medicine

Attending Physician Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Kimberly Molina, MD

Assistant Professor of Pediatrics Division of Pediatric Cardiology University of Utah

Salt Lake City, Utah

Divya Moodalbail, MD

Pediatric Nephrology Fellow The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

xviii r r r Contributing Authors

Frances M Nadel, MD, MSCE

Associate Professor, Clinical Pediatrics

Department of Pediatrics

Perelman School of Medicine at the

University of Pennsylvania

Attending Physician

Division of Emergency Medicine

Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania

Luz I Natal-Hernandez, MD

Pediatric Cardiology

UCSF Medical Center

San Francisco, California

Neuroscience Therapeutic Area

Janssen Research and Development LLC

Janssen Pharmaceutical Companies of

Johnson & Johnson

Titusville, New Jersey

Jason G Newland, MD, Med

Associate Professor of Pediatrics

Children’s Mercy Hospitals & Clinics

University of Kansas City, Missouri

Jessica Newman, DO

Fellow

Division of Infectious Diseases

Department of Internal Medicine

University of Kansas Medical Center

Kansas City, Kansas

Ross Newman, DO

Assistant Professor of Pediatrics

University of Missouri-Kansas City

Children’s Mercy Hospital and Clinics

Kansas City, Missouri

Thomas Nguyen, MD

Assistant Program Director

Residency

Department of Emergency Medicine

Albert Einstein College of Medicine of

Veshiva University

New York City, New York

Sheila M Nolan, MD, MSCE

Global Medical Monitor

Vaccine Clinical Research

Pfizer Inc.

Pearl River, New York

Robert Noll, MD, FAAP

Director Pediatric Hospital Medicine and Emergency Care

Department of Pediatrics Crozer-Chester Medical Center Chester, Pennsylvania

Clinical Assistant Professor of Pediatrics Jefferson Medical College of Thomas Jefferson University

Bruce A Ong, MD, MPH

Pediatric Pulmonary Fellow Division of Pulmonary Medicine and Cystic Fibrosis Center

The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Kevin C Osterhoudt, MD, MS, FAAP, FAACT, FACMT

Medical Director The Poison Control Center The Children’s Hospital of Philadelphia Associate Professor of Pediatrics and Emergency Medicine

The Perelman School of Medicine at the University of Pennsylvania

Philadelphia, Pennsylvania

Erica Pan, MD, MPH, FAAP

Associate Clinical Professor Department of Pediatrics Division of Infectious Diseases University of California, San Francisco San Francisco, California

Deputy Health Officer Director

Division of Communicable Disease Control & Prevention

Alameda County Public Health Department Oakland, California

Howard B Panitch, MD

Professor of Pediatrics Perelman School of Medicine University of Pennsylvania Director of Clinical Programs Division of Pulmonary Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Rita Panoscha, MD

Clinical Associate Professor Department of Pediatrics The Child Development and Rehabilitation Center and Oregon Health and Science University

Portland, Oregon

Juliann M Paolicchi, MA, MD

Director Pediatric Comprehensive Epilepsy Center Associate Professor

Weill Cornell Medical Center New York City, New York

Carolyn Paris, MD

Attending Physician Department of Emergency Medicine Seattle Children’s Hospital

Assistant Professor University of Washington School of Medicine

Department of Pediatrics University of South Florida

Christopher J Petit MD

Assistant Professor Lillie Frank Abercrombie Section of Cardiology

Department of Pediatrics Texas Children’s Hospital Baylor College of Medicine Houston, Texas

Virginia M Pierce MD

Fellow Division of Infectious Diseases Department of Pediatrics Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Contributing Authors r r r xix

Nelangi M Pinto, MD, MSCI

Division of Adolescent Medicine

Children’s Hospital of Pittsburgh

Jill C Posner, MD, MSCE

Associate Professor of Clinical Pediatrics

Department of Pediatrics

The Children’s Hospital of Philadelphia

Perelman School of Medicine

The University of Pennsylvania

Children’s Hospital of Philadelphia

University of Pennsylvania Perelman

Seattle Children’s Hospital Seattle, Washington

Anne F Reilly, MD, MPH

Associate Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

Assistant Professor of Pediatrics Jefferson Medical College Philadelphia, Pennsylvania

David C Rettew, MD

Associate Professor of Psychiatry and Pediatrics

Program Director Child & Adolescent Psychiatry Fellowship Director

Pediatric Psychiatry Clinic Vermont Center for Children, Youth, and Families

Burlington, Vermont

Michelle T Rook, MD, MSc

Assistant Professor Division of Gastroenterology, Hepatology and Nutrition

The Children’s Hospital of Philadelphia University of Pennsylvania

Philadelphia, Pennsylvania

Howard M Rosenberg, DDS, MSD, Med

Associate Professor Pediatric Dentistry Department of Preventive and Restorative Sciences

University of Pennsylvania School of Dental Medicine

Philadelphia, Pennsylvania

Marianne Ruby, MD

Clinical Instructor Department of Obstetrics and Gynecology

Thomas Jefferson University Philadelphia, Pennsylvania

Rebecca L Ruebner, MD

Department of Pediatrics Division of Nephrology Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Richard M Rutstein, MD

Medical Director Special Immunology Service Children’s Hospital of Philadelphia Professor of Pediatrics

Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

Matthew J Ryan, MD

Assistant Professor of Pediatrics

xx r r r Contributing Authors

Ann E Salerno, MD

Division Chief, Pediatric Nephrology

UMass Memorial Children’s Medical

Center

Assistant Professor of Pediatrics

University of Massachusetts Medical

School

Worcester, Massachusetts

Denise A Salerno, MD, FAAP

Pediatric Clerkship Director

Associate Chair for Undergraduate

C.S Motts Children’s Hospital

Ann Arbor, Michigan

Wudbhav N Sankar, MD

Assistant Professor of Orthpaedic Surgery

Children’s Hospital of Philadelphia

University of Pennsylvania School of

The Royal Children’s Hospital

Pediatric Gastroenterology Department

Monash Medical Centre

Charles I Schwartz, MD, FAAP

Assistant Clinical Professor of Pediatrics

University of Pennsylvania Perelman

Jefferson Medical College Thomas Jefferson University Philadelphia, Pennsylvania Nemours/Alfred I duPont Hospital for Children

Wilmington, Delaware

Edisio Semeao, MD

Attending Physician Department of Gastroenterology Division of Gastroenterology, Hepatology and Nutrition

The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Deborah Sesok-Pizzini, MD, MBA

Medical Director Blood Bank and Transfusion Medicine The Children’s Hospital of Philadelphia Associate Professor of Clinical Pathology and Laboratory Medicine

Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

Christine B Sethna, MD, EdM

Assistant Professor Hofstra School of Medicine Interim Divisional Director Pediatric Nephrology Cohen Children’s Medical Center of New York

New Hyde Park, New York

Kara N Shah, MD, PhD

Director Division of Dermatology Cincinnati Children’s Hospital Associate Professor

Departments of Pediatrics and Dermatology

University of Cincinnati College of Medicine

Cincinnati, Ohio

Samir S Shah, MD, MSCE

Director Division of Hospital Medicine Cincinnati Children’s Hospital Medical Center

Associate Professor Department of Pediatrics University of Cincinnati College of Medicine

Cincinnati, Ohio

Julia F Shaklee, MD

Division of Pediatric Infectious Diseases The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Raanan Shamir, MD

Chairman Institute of Gastroenterology, Nutrition and Liver Diseases

Schneider Children’s Medical Center of Israel

Professor of Pediatrics Sackler Faculty of Medicine Tel-Aviv University

Israel

Andi L Shane, MD, MPH

Assistant Professor Division of Infectious Diseases Emory University School of Medicine Atlanta, Georgia

David D Sherry, MD

Chief Rheumatology Section Professor of Pediatrics The Children’s Hospital of Philadelphia University of Pennsylvania

Philadelphia, Pennsylvania

Aseem R Shukla, MD, FAAP

Director Pediatric Urology Associate Professor of Urology and Pediatrics

University of Minnesota Amplatz Children’s Hospital

Minneapolis, Minnesota

Daniel Shumer, MD

Pediatric Chief Resident Vermont Children’s Hospital University of Vermont Burlington, Vermont

Alyssa Siegel, MD

Clinical Assistant Professor Division of General Pediatrics The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Hugh Silk, MD, MPH, FAAFP

Clinical Associate Professor University of Massachusetts Medical School

Department of Family Medicine and Community Health

Family Medicine Residency – Hahnemann Family Health Center

Worcester, Massachusetts

Contributing Authors r r r xxi

Michael J Smith, MD, MSCE

Assistant Professor of Pediatrics

University of Louisville School of Medicine

Louisville, Kentucky

Sabrina E Smith, MD, PhD

Adjunct Assistant Professor of Neurology

University of Pennsylvania School of

Medicine

Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania

Howard M Snyder, III, MD

Director of Surgical Teaching

Seattle Children’s Hospital/University of

Washington School of Medicine

Assistant Professor Department of Pediatrics Perelman School of Medicine University of Pennsylvania Attending Physician Division of Infectious Diseases The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Julie W Stern, MD

Clinical Associate Professor University of Pennsylvania Division of Oncology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Sheila Stille, DMD

Program Director General Practice Residency in Dentistry University of Massachusetts

Worcester, Massachusetts

Kathleen E Sullivan, MD, PhD

Chief Division of Allergy and Immunology Professor of Pediatrics

Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

John I Takayama, MD, MPH

Professor of Clinical Pediatrics Department of Pediatrics University of California San Francisco UCSF Benioff Children’s Hospital San Francisco, California

Ronn E Tanel, MD

Associate Professor of Pediatrics Department of Pediatrics UCSF School of Medicine Director

Pediatric Arrhythmia Center Division of Pediatric Cardiology UCSF Benioff Children’s Hospital San Francisco, California

Jesse A Taylor, MD

Assistant Professor Co-Director CHOP Cleft Team Plastic, Reconstructive, and Craniofacial Surgery

The University of Pennsylvania and Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

David T Teachey, MD

Assistant Professor Department of Pediatrics Divisions of Pediatric Hematology and Oncology

Blood and Marrow Transplant Children’s Hospital of Philadelphia University of Pennsylvania, School of Medicine

Michelle Terry, MD

Clinical Associate Professor Department of Pediatrics University of Washington Seattle, Washington

Sunil Thummala, MD, MBA

Neurologist Paris Regional Medical Center Paris, Texas

Leonel Toledo, MD

xxii r r r Contributing Authors

Professor of Clinical Pediatrics

University of Pennsylvania School of

Medicine

Medical Director

Emergency Transport Team

Associate Medical Director

Emergency Department

The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania

Shamir Tuchman, MD, MPH

Assistant Professor of Pediatrics

Division of Pediatric Nephrology

Children’s National Medical Center

George Washington University School of

Medicine

Washington, DC

Judith A Turow, MD, FAAP

Clinical Associate Professor of Pediatrics

Division of General Pediatrics

Thomas Jefferson University Hospital

Daniel Walmsley, DO, FAAP

Assistant Professor of Pediatrics Department of Pediatrics Jefferson Medical College/Nemours Pediatrics

Philadelphia, Pennsylvania

Katherine A Wayman, MD

Chief Resident Neurology Fletcher Allen Health Care Burlington, Vermont

Jessica Wen, MD

Assistant Professor of Pediatrics Division of Gastroenterology, Hepatology and Nutrition

The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Peter Weiser, MD

Assistant Professor Division of Pediatric Rheumatology Department of Pediatrics

Children’s Hospital of Alabama University of Alabama at Birmingham Birmingham, Alabama

Alexis Weymann

Pediatric Residency Program The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Terri Brown Whitehorn, MD

Assistant Professor of Clinical Pediatrics Perelman School of Medicine – University

of Pennsylvania Philadelphia, Pennsylvania

Sarah E Winters, MD

Attending Physician Primary Care The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Char M Witmer, MD, MSCE

Assistant Professor Department of Pediatrics Division of Hematology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Margaret Wolff, MD

Fellow in Pediatric Emergency Medicine University of Pennsylvania School of Medicine

Division of Emergency Medicine Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Tracie Wong, MD

Assistant Professor of Pediatrics University of Pennsylvania School of Medicine

Attending Physician Division of GI, Hepatology and Nutrition Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

George A (Tony) Woodward, MD, MBA

Chief Division of Emergency Medicine Medical Director

Transport Services Seattle Children’s Hospital Professor of Pediatrics University of Washington School of Medicine

Seattle, Washington

Paige L Wright, MD

Assistant Professor Department of Pediatrics University of Washington School of Medicine

Academic Faculty Emergency Services Department Children’s Hospital and Regional Medical Center

Seattle, Washington

Hsi-Yang Wu, MD

Associate Professor of Urology Stanford University Medical Center Lucile Packard Children’s Hospital Palo Alto, California

Albert C Yan, MD

Chief Section of Pediatric Dermatology Children’s Hospital of Philadelphia Associate Professor

Pediatrics and Dermatology Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

Contributing Authors r r r xxiii

Professor of Surgery in Urology

The Perelman School of Medicine at the

University of Pennsylvania

The John W Duckett Endowed Chair

The Children’s Hospital of

Karen P Zimmer, MD, MPH, FAAP

Assistant Professor Johns Hopkins School of Medicine Medical Director

ECRI Institute Baltimore, Maryland

Raezelle Zinman, MDCM

Clinical Professor of Pediatrics University of Pennsylvania Division of Pulmonary Medicine Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Kathleen M Zsolway, DO

Medical Director General Pediatrics Faculty Practice The Children’s Hospital of

Philadelphia Clinical Associate Professor of Pediatrics

University of Pennsylvania Philadelphia, Pennsylvania

Attention-Deficit/Hyperactivity Disorder (ADHD) 86

Autism/Pervasive Developmental Disorder (PDD)

Avascular (Aseptic) Necrosis of the Femoral Head

xxvi r r r Contents

Cavernous Transformation and Portal Vein

22q11.2 Deletion Syndrome (Digeorge Syndrome) 258

Disseminated Intravascular Coagulation 286

Functional Diarrhea of Infancy or ToddLer’s Diarrhea 350

Fungal Skin Infections (Dermatophyte Infections,

Human Immunodeficiency Virus Infection 432

Metabolic Diseases in Hypoglycemic Newborns 544

Metabolic Diseases in Acidotic Newborns 546

Metabolic Diseases in Hyperammonemic Newborns 548

Parvovirus B19 (Erythema Infectiosum, Fifth Disease) 622

Contents r r r xxix

Pneumoystic Jiroveci (Previously known as

Pneumocystic Carinii Pneumonis) 658

Porencephaly Cortical Dysplasia/Neuronal Migration

Disorders—Malformations of Cortical Development 674

Prion Diseases (Transmissible Spongiform

Protein-Energy Malnutrition (Kwashiorkor) 694

Severe Acute Respiratory Syndrome (SARS) 784

Sleep Apnea—Obstructive Sleep Apnea Syndrome 802

Transient Erythroblastopenia of Childhood 894

Transient Tachypnea of the Newborn (TTN) 896

The 5-Minute Pediatric

Consult SIXTH EDITION

ABDOMINAL MASS

Rose C Graham

BASICS

DEFINITION

An unusually enlarged abdominal or retroperitoneal

organ (i.e., hepatomegaly, splenomegaly, or enlarged

kidney) or a defined fullness in the abdominal cavity

not directly associated with an abdominal organ

EPIDEMIOLOGY

r60% of abdominal masses in children are due to

organomegaly

r40% of abdominal masses in children are due to

anomalies of development, neoplasms, or

– Hepatomegaly due to intrinsic liver disease:

◦ Hepatitis (viral, autoimmune)

◦ Metabolic disorders (Wilson disease, glycogen

storage disease)

◦ Congenital hepatic fibrosis

– Cystic disease (Caroli disease)

– Tumor (hepatic adenoma, hepatoblastoma,

hepatocellular carcinoma or diffuse neoplastic

process such as lymphoma)

– Vascular tumor (hamartoma, hemangioma,

hemangioendothelioma)

– Vascular obstruction/congestion (Budd–Chiari

syndrome, congestive heart failure)

– Focal nodular hyperplasia

rSpleen

– Storage disease (Gaucher, Niemann–Pick)

– Langerhans cell histiocytosis

– Leukemia

– Hematologic (hemolytic disease, sickle cell

disease, hereditary spherocytosis/elliptocytosis)

– Wandering spleen

rPancreas– Pseudocyst (trauma)– Pancreatoblastoma

rGallbladder/biliary tract– Choledochal cyst– Hydrops– Obstruction (stone, stricture, trauma)

rKidney– Multicystic dysplastic kidney– Hydronephrosis/ureteropelvic obstruction– Polycystic disease

– Wilms tumor– Renal vein thrombosis– Cystic nephroma– Mesoblastic nephroma

rBladder– Posterior urethral valves– Neurogenic bladder

rAdrenal– Adrenal hemorrhage– Adrenal abscess– Neuroblastoma– Pheochromocytoma

rUterus– Pregnancy– Hematocolpos– Hydrometrocolpos

rOvary– Cysts (dermoid, follicular)– Torsion

– Germ cell tumor

rPeritoneal– Ascites– Teratoma

rAbdominal wall– Umbilical/inguinal/ventral hernia– Omphalocele/gastroschisis– Trauma (rectus hematoma)– Tumor (fibroma, lipoma, rhabdomyosarcoma)

rOmentum/mesentery– Cysts

– Mesenteric fibromatosis

◦ Mesenteric adenitis– Tumors (liposarcoma, leiomyosarcoma,fibrosarcoma, mesothelioma)

rOther– Lymphangioma– Fetus in fetu– Sacrococcygeal teratoma

APPROACH TO THE PATIENT

When evaluating a pediatric abdominal mass, anorganized approach is paramount in determining itsetiology

rPhase 1: Determine the location of the abdominalmass and its association with intra-abdominalorgans via a thorough and careful abdominalexamination

rPhase 2: Perform diagnostic tests:

– Ultrasound is the most efficient way to start theevaluation

Hints for Screening Problems

rIn neonates, a palpable liver edge can be normal;the total liver span is most important

rIn infants, a full bladder is often mistaken for anabdominal mass

rIn infants, most abdominal masses are of renalorigin and nonmalignant

rSevere constipation in older children andadolescents can present as a large, hard massextending from the pubis past the umbilicus

rGastric distention should be considered in allchildren who present with a tympanitic epigastricmass

HISTORY

rQuestion: Weight loss?

rSignificance: Tumor, inflammatory bowel disease

rQuestion: Fever?

rSignificance: Abscess, malignancy

rQuestion: Jaundice?

rSignificance: Liver/biliary disease

rQuestion: Hematuria or dysuria?

rSignificance: Renal disease

rQuestion: Vomiting?

rSignificance: Intestinal obstruction

rQuestion: Frequency and quality of bowelmovements?

rSignificance: Constipation, intussusception,compression of bowel by mass

rQuestion: Bleeding or bruising?

rSignificance: Coagulopathy

rQuestion: History of abdominal trauma?

rSignificance: Pancreatic pseudocyst, duodenalhematoma

rQuestion: Sexual activity?

– In adolescent-aged girls, ovarian disorders,hematocolpos, and pregnancy are more commoncauses of abdominal masses

ABDOMINAL MASS

A

PHYSICAL EXAM

rFinding: General appearance?

rSignificance: Ill-appearance or cachexia point

toward infection or malignancy

rFinding: Location of abdominal mass?

rSignificance:

– Left lower quadrant: Constipation, ovarian

process, ectopic pregnancy

– Left upper quadrant: Anomaly of the kidney or

splenomegaly

– Right lower quadrant: Abscess (inflammatory

bowel disease), intestinal phlegmon, appendicitis,

intussusception, ovarian process, ectopic

pregnancy

– Right upper quadrant: Involves liver, gallbladder,

biliary tree, or intestine

– Epigastric: Abnormality of the stomach (bezoar,

torsion), pancreas (pseudocyst), or enlarged liver

– Suprapubic: Pregnancy, hydrometrocolpos,

hematocolpos, posterior urethral valves

– Flank: Renal disease (cystic kidney,

hydronephrosis, Wilms tumor)

rFinding: Characteristics of abdominal mass?

rSignificance: Mobility, tenderness, firmness,

smoothness, and/or irregularity of the surface of the

mass can provide clues to its significance

rFinding: Hard and immobile mass?

rSignificance: Tumor

rFinding: Extension of mass across midline or into

pelvis?

rSignificance: Tumor, hepatomegaly, splenomegaly

rFinding: Percussion of mass?

rSignificance: Dullness indicates a solid mass;

tympany indicates a hollow viscus

rFinding: Shifting dullness, fluid wave?

rSignificance: Ascites

rFinding: Skin exam?

rSignificance: Bruising and petechiae may occur with

coagulopathy related to liver disease and malignant

infiltration of bone marrow; caf ´e au lait spots are

associated with neurofibromas

rFinding: Lymphadenopathy or lymphadenitis?

rSignificance: Systemic process either malignant or

infectious

DIAGNOSTIC TESTS & INTERPRETATION

rTest: CBC

rSignificance: Anemia or hemolysis

rTest: Chemistry panel

rSignificance:

– Renal disease: BUN and creatinine levels

– Liver disease (bilirubin, ALT, AST, alkaline

phosphatase, GGT, albumin, PT/PTT)

– Gallbladder disease (bilirubin, GGT)

Imaging

rPlain abdominal radiographs:

– Rule out intestinal obstruction, identifycalcifications, fecal impaction

rCT scan:

– Can provide more detail when there is overlyinggas or bone; if malignancy is suspected should dochest, abdomen, and pelvis CT

rMRI:

– Vascular lesions of liver, major vessels, and tumors

rRadioisotope cholescintigraphy (HIDA) scan:

– Liver, gallbladder

◦ Meckel scan can identify gastric mucosacontained within a Meckel diverticulum orintestinal duplication

rVoiding cystourethrography or intravenousurography:

– Wilms tumor, cystic kidney disease, posteriorurethral valves, hydronephrosis

rUpper GI study and barium enema:

– May be of benefit when the mass involves theintestine

rThe remaining causes of abdominal masses requireurgent care and timely evaluation and referral toappropriate specialists

ISSUES FOR REFERRAL

Except for the diagnosis of constipation, the presence

of an abdominal mass requires immediate attention,and diagnostic studies should be performedexpeditiously at a facility capable of diagnosingpediatric disorders

– Pancreatitis (pseudocyst)

rThe remaining causes of abdominal masses requireurgent care and timely evaluation and referral toappropriate specialists

ADDITIONAL READING

rChandler JC, Gauderer MWL The neonate with an

abdominal mass Pediatr Clin North Am 2004;51:

rMahaffey SM, Rychman RC, Martin LW Clinical

aspects of abdominal masses in children Semin

Roentgenol 1988;23:161–174.

rMerten DF, Kirks DR Diagnostic imaging of pediatric

abdominal masses Pediatr Clin North Am.

r R16.0 Hepatomegaly, not elsewhere classified

r R16.1 Splenomegaly, not elsewhere classified

r R19.00 Intra-abd and pelvic swelling, mass andlump, unsp site

Recurrent attacks of periumbilical pain with nausea,

vomiting, anorexia, headache, and pallor

EPIDEMIOLOGY

Incidence

rOccurs mostly in children, with a mean onset at age

7 year (3–10 years)

rPeak symptoms 10–12 years of age

rMore common in girls (3:2)

Prevalence

rMay affect as many as 1–4% of children at some

point in their lives

rDeclining frequency toward adulthood

RISK FACTORS

Genetics

Parents of affected children often have history of

migraine headaches and motion sickness

ETIOLOGY

rMay involve neuronal activity originating in the

hypothalamus with involvement of the cortex and

autonomic nervous system

rSerotonin is implicated, and blockade of serotonin

receptors may prevent abdominal migraine

rMay involve some as yet ill-defined local intestinal

vasomotor factors

DIAGNOSIS

Rome III criteria—2 episodes within 12 months

meeting all of the following criteria:

rParoxysmal intense periumbilical pain that lasts

>1 hour

rIntervening episodes of health between episodes

rPain that interferes with activity

rPain associated with≥2 of the following: Anorexia,

nausea, vomiting, headache, photophobia, or pallor

rNo evidence of inflammatory, anatomic, metabolic,

or neoplastic process

HISTORY

rPain usually lasts<6 hours.

rPain can be located anywhere in abdomen, butmore often in upper quadrants

rNo abdominal pain between attacks

rRepetition of identical abdominal crises, anywherefrom 1 time per week to several times a year

rMigraine in the history of patient or relatives

rOccasionally, other migraine phenomena such asnausea, vomiting, perspiration, body temperaturechanges, focal paresthesias, radiation of pain to alimb, visual disturbances, or general malaise

rImpaired consciousness (some degree of lethargymay occur)

rAsk about a family history of migraine headache orunexplained bouts of abdominal pain as children

DIAGNOSTIC TESTS & INTERPRETATION

rEven if a patient meets most criteria for abdominalmigraine, studies as outlined below should bestrongly considered to ensure that a more seriousdisorder does not exist

rAbdominal migraine is a diagnosis of exclusion.

Diagnostic Procedures/Radiologic Imaging

rObstruction series to assess for intermittent orpartial bowel obstruction

rUpper GI to rule out anatomic abnormalities

rUS or CT scan to rule out mass lesion or chronicappendicitis

rRenal US to rule out ureteropelvic junction (UPJ)obstruction

rBarium enema (during painful crisis) to rule outintussusception

rEEG may help differentiate between abdominalmigraine and epilepsy

rVisual evoked response (VER) to red and whiteflashlight: Children with abdominal migraine maydisplay a specific fast-wave activity response

rRarely, brain imaging with CT or MRI may be usefulfor evaluating causes of intermittent hydrocephalus

– Abdominal epilepsy—but has a shorter duration

of pain (minutes), altered consciousness during

event, abrupt onset, abnormal discharges in EEG

in 80%

– Temporal lobe epilepsy

– Intermittent hydrocephalus (possibly secondary to

a 3rd ventricle colloid cyst)

ALERT

Because it is usually a diagnosis of exclusion, many

patients go through a large workup to rule out other

causes of pain, sometimes including laparotomy

TREATMENT

MEDICATION (DRUGS)

rMedications can be used to abort acute attacks or

be taken as daily prophylaxis

rFor most patients, risks of side effects and

complications from the use of these medications

may outweigh the relief of pain, especially in

children who are experiencing infrequent episodes

rLimited data exist on abortive agents for abdominal

migraines; however, several agents have shown

benefit in specialty-based clinical practice, including

metoclopramide, steroids, intranasal sumatriptan,

and NSAIDs (although the latter may be avoided if

there are clinical concerns for gastritis or peptic ulcer

disease) Consider benzodiazepines (i.e lorazepam)

and antiemetics (i.e odansetron) for vomiting

predominant symptoms

rSuggested prophylactic treatments are similar to

those for migraine headaches and include tricyclic

antidepressants (e.g., amitriptyline), topiramate,

propranolol, cyproheptadine, and valproic acid If

EEG or other data point to possible epilepsy, empiric

treatment with anticonvulsants may be considered

– Avoiding triggers is the most optimal strategy for

preventing recurrent attacks:

◦ Common triggers include caffeine, nitrites,

amines, emotional arousal, travel, prolonged

fasting, altered sleep, exercise, and/or flickering

r10% of children who have a diagnosis of migraineheadaches have previously suffered fromunexplained recurrent abdominal pain

rAdult migraine headache sufferers experienceabdominal pain more frequently than do tensionheadache sufferers

PATIENT EDUCATION

rTo help child during bouts of pain, allow the child to

do whatever makes him or her comfortable—rest,positioning, quiet

rWhether the patient should be excused from schooldepends on various factors:

– Frequency, severity, and duration of pain– Age, maturity, and coping skills of the child

ADDITIONAL READING

rCatto-Smith AG, Ranuh R Abdominal migraine and

cyclical vomiting Semin Pediatr Surg 2003;12(4):

254–258

rCuvellier JC, L ´epine A Childhood periodic

syndromes Pediatr Neurol 2010;42(1):1–11.

rLewis DW Pediatric migraine Neurol Clin.

2009;27(2):481–501

rLi BU, Balint JP Cyclic vomiting syndrome: Evolution

in our understanding of a brain-gut disorder Adv

Pediatr 2000;47:117–160.

rPopovich DM, Schentrup DM, McAlhany AL.

Recognizing and diagnosing abdominal migraines

J Pediatr Health Care 2010;24(6):372–377.

rRasquin A, Di Lorenzo C, Forbes D, et al Childhoodfunctional gastrointestinal disorders: Child/

adolescent Gastroenterology 2006;130:

1527–1537

rRussell G, Abu-ArafehI, Symon DN Abdominalmigraine: Evidence for existence and treatment

options Pediatr Drugs 2002;4:1–8.

rTan V, Sahami AR, Peebes R, et al Abdominalmigraine and treatment with intravenous valproic

acid Psychosomatics 2006;47(4):353–355.

rWeydert JA, Ball TM, Davis MF Systematic review of

treatments for recurrent abdominal pain Pediatrics.

rQ: What can I do to help my child during bouts ofpain?

rA: First, allow the child to do whatever makes him

or her comfortable This may mean resting,positioning, or being quiet Acetaminophen orNSAID based pain relievers may help to a certaindegree Whether the patient should be excused fromschool depends on various factors such as thefrequency, severity, and duration of the pain as well

as the age, maturity, and coping skills of the child

ABDOMINAL PAIN

Kurt A Brown

BASICS

DEFINITION

A child’s complaint of abdominal pain can originate

from GI and non-GI causes but also commonly can be

the manifestation of referred pain from

– Gastroenteritis (bacterial, viral or parasitic)

– Helicobacter pylori gastritis

– Intestinal foreign body

– Heavy-metal (i.e., lead) ingestion

– Inflammatory bowel disease– Intestinal adhesions– Mesenteric adenitis– Necrotizing enterocolitis– Pancreatitis

– Peptic ulcer or gastritis– Esophagitis or duodenitis

rFunctional– Depression– Functional abdominal pain– Malingering

– Munchausen syndrome (+/− by proxy)

– Stress

rMiscellaneous– Abdominal migraine– Cholelithiasis– Colic– Constipation– Dysmenorrhea– Ectopic pregnancy– Endometriosis– Ileus– Intestinal pseudo-obstruction– Irritable bowel syndrome– Lactose intolerance– Mittelschmerz– Nephrolithiasis– Ovarian cyst– Pregnancy– Porphyria– Sickle cell disease– Typhlitis

APPROACH TO THE PATIENT

rPhase 1: Careful and complete history andphysical exam to narrow this extensive differentialdiagnosis:

– Identify emergencies– Separate acute pain conditions from chronic pain

rPhase 2: Directed laboratory evaluations should bemade to support more likely portions of thedifferential diagnosis

HISTORY

rQuestion: Location and duration of pain?

rSignificance: Acute vs chronic illness

rQuestion: Onset and progression of symptoms?

rSignificance: Evolution of painful process

rQuestion: Presence of hematochezia?

rSignificance: Colonic bleeding or massive upper GIbleeding

rQuestion: Abdominal distention?

rSignificance: Distention of an abdominal viscus byair, stool, or fluid

rQuestion: Radiation of pain?

rSignificance: Certain entities characteristically haveradiation of pain (i.e., pancreatitis to the back,appendicitis to the right lower quadrant)

rQuestion: Pain relieved by bowel movements?

rSignificance: Etiology may be related to colonicdistension (by air or stool) or inflammation (colitis)

rQuestion: Bowel movement pattern: Decrease infrequency or change in caliber?

rSignificance: Constipation, tumor, or somethingelse?

rQuestion: Relationship to emesis?

rSignificance: Usually upper intestinal tractobstruction, liver or gall bladder disorders (painetiology—see Table 1)

rQuestion: Signs and symptoms of abdominal pain?

rSignificance: The farther the complaint of pain isaway from the periumbilical region, the more likelythe pain etiology represents organic disease Truenighttime waking with pain is more often correlatedwith organic disease than functional pain

PHYSICAL EXAM

rFinding: Location of pain?

rSignificance: See Table 1

rFinding: Re-examination by the same health careprovider for changing characteristics?

rSignificance: Evolution of abdominal process

rFinding: Rebound tenderness?

rSignificance: Peritoneal irritation from peritonitis orappendicitis; potential need for surgical intervention

rFinding: Rectal examination?

rSignificance: Peritoneal irritation, further localization

of pain, masses, presence and consistency of stool,and/or occult heme

DIAGNOSTIC TESTS & INTERPRETATION

rTest: CBC with differential

rSignificance: Total WBC count is nonspecific andmay be a poor indicator of intestinal inflammation.Anemia is seen in lead poisoning, malignancy, andbleeding Low platelets are seen in hypersplenism

rTest: Comprehensive metabolic panel

rSignificance: Sodium, potassium, chloride, carbondioxide, blood urea nitrogen, creatinine, glucose,total protein, albumin, alanine aminotransferase,uric acid, lactate dehydrogenase

TREATMENT

General Measures

rEvery effort should be made to ensure that thepatient is clinically stable

rFrequent evaluation of vital signs and physical exam

is a means of assessing evolving pain and ensuringthat the patient is well enough for potentialdischarge

ISSUES FOR REFERRAL

Persistent abdominal pain without clear etiology orchronic GI diseases should be referred to a pediatricgastroenterologist

ABDOMINAL PAIN

A

Table 1 Classic clinical findings in disorders characterized by abdominal pain

Disorder Typical clinical picture Definitive diagnostic test

Peptic ulcer disease Burning or sharp midepigastric pain that occurs 1–3 hours after meals and is

exacerbated by spicy food and relieved by antacids; family history of pepticulcer disease

Endoscopy

Pancreatitis Episodic left upper quadrant pain or epigastic that occurs 5–10 minutes after

meals, radiates to the back, and is exacerbated by fatty foods

Pancreatic ultrasound or CT scanSerum amylase and lipasis level (↑)Urinary tract infection Suprapubic pain, burning on urination, urinary frequency, urinary urgency Urine culture

UrinalysisRenal calculi Severe periodic cramping pain that occurs in the flank and occasionally radiates

to the groin; costovertebral angle tenderness; family history of renal calculi

UrinalysisRenal ultrasoundPeriappendiceal abscess Right lower quadrant pain; rebound and direct tenderness; anorexia and

Gallbladder disease Right upper quadrant pain that occurs 5–10 minutes after meals and is

exacerbated by fatty foods; family history of gallstones Gallbladder ultrasound

Functional abdominal pain

(irritable bowel syndrome)

Cramping periumbilical pain that is exacerbated by eating and relieved bydefecation

Trial with Metamucil

Lactose intolerance Cramping periumbilical pain that increases following ingestion of dairy products

and is accompanied by flatulence and bloating Trial with a milk-free dietBreath hydrogen study for lactose deficiencyInflammatory bowel disease Right lower quadrant cramping and tenderness; anemia; guaiac-positive stool Colonoscopy

Barium enemaUpper GI seriesESR (↑), platelet count (↑), WBC count (↑)Esophagitis Epigastric and substernal pain that is relieved by antacids and exacerbated by

lying down; history of iron deficiency; anemia; guaiac-positive stool

Endoscopy

Lead poisoning Abdominal pain; history of pica; microcytic anemia; basophilic stippling Serum lead level

Pancreatic pseudocyst Left upper quadrant pain; recurrent vomiting; history of abdominal pain Abdominal ultrasound

Sickle cell disease Periumbilical pain that responds to rest and rehydration Sickle cell preparation

Hemoglobin electrophoresisAbdominal epilepsy Periodic severe abdominal pain that is often associated with seizures Trial with anticonvulsants

Abdominal migraine Severe abdominal pain; family history of migraine; recurrent headache, fever, and

vomiting; unilateral or occipital headache; somatic complaints Trial with antimigraine medicationsDepression Social withdrawal; decreased activity; irritability; poor attention span; difficulty

sleeping

Trial with antidepressant medications

School avoidance Nonspecific abdominal pain; severe anxiety reaction; pain that is more severe on

weekdays and improves on weekends

CT, computed tomography; ESR, erythrocyte sedimentation rate; GI, gastrointestinal; NSAIDS, nonsteroidal antiinflammatory drugs; UTI, urinary tract infection; WBC, white blood cell;↑, increased

ADDITIONAL READING

rAlfven G One hundred cases of recurrent abdominal

pain in children: Diagnostic procedures and criteria

rCollins BS, Thomas DW Chronic abdominal pain.

Pediatr Rev 2007;28(9):323–331 [erratum appears

ABNORMAL BLEEDING

Char Witmer

BASICS

DEFINITION

Abnormal bleeding may present as:

rFrequent or significant mucocutaneous bleeding

(epistaxis, bruising, gum bleeding, or menorrhagia)

rBleeding in unusual sites such as muscles, joints, or

internal organs

rExcessive postsurgical bleeding

ETIOLOGY

Abnormal bleeding can be the result of a coagulation

factor deficiency, an acquired or congenital disorder of

platelet number or function, or inherited or acquired

collagen vascular disorders

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

Platelet disorders may be quantitative or qualitative,

collagen vascular disorders can be acquired or

inherited, and disorders of coagulation factors can be

◦ Drug-associated marrow suppression

◦ Virus-associated marrow suppression (e.g., HIV)

– Neonatal alloimmune thrombocytopenia

– Maternal autoimmune thrombocytopenia

– Drug induced (heparin, sulfonamides, digoxin,

chloroquine)

– Sepsis/disseminated intravascular coagulopathy

– Infection: Viral, bacterial, fungal, rickettsial

– Microangiopathic process (e.g., thrombotic

thrombocytopenic purpura/hemolytic uremic

– Drugs (e.g., aspirin, NSAIDs, guaifenesin,antihistamines, phenothiazines, anticonvulsants)– Uremia

– Paraproteinemia

rCoagulation disorders– Prolongation of activated partial thromboplastintime (aPTT):

◦ Deficiency of factor VIII, IX, XI, or XII

◦ Acquired inhibitor or lupus anticoagulant

◦ Von Willebrand disease (aPTT may benormal)

– Prolongation of prothrombin time (PT):

◦ Mild vitamin K deficiency

◦ Liver disease, mild to moderate

◦ Deficiency of factor VII

◦ Factor VII inhibitor– Prolongation of PT and aPTT:

◦ Liver disease, severe

◦ Disseminated intravascular coagulopathy

◦ Severe vitamin K deficiency

◦ Hemorrhagic disease of the newborn

◦ Deficiency of factor II, V, or X or fibrinogen

◦ Dysfibrinogenemia

◦ Hypoprothrombinemia associated with a lupusanticoagulant

– Normal screening laboratory tests:

◦ Von Willebrand disease

◦ Factor XIII deficiency

◦ Alpha-2-antiplasmin deficiency

◦ Plasminogen activator inhibitor-I deficiency

rVessel wall disorders– Congenital:

◦ Hereditary hemorrhagic telangiectasia

◦ Ehlers–Danlos syndrome

◦ Osteogenesis imperfecta

◦ Marfan syndrome– Acquired:

◦ Vasculitis (systemic lupus erythematosus,Henoch–Sch ¨onlein purpura, and others)

◦ Scurvy

APPROACH TO THE PATIENT

rPhase 1– Includes a thorough history and physical exam– Familial history specifically of bleeding orconsanguinity is an important component of thisphase

– Standard screening laboratory tests include PT,aPTT, and platelet count

rPhase 2– If a bleeding disorder is suspected but the initialscreening tests are negative, testing for vonWillebrand disease, factor XIII deficiency, anddysfibrinogenemia is warranted

– Consider platelet aggregation studies

rPhase 3– Any abnormal screening tests need furtherevaluation with additional testing to define thespecific disorder (e.g., factor assays)

HISTORY

By taking into account the patient’s age, sex, clinicalpresentation, past medical history, and family history,the most likely cause of bleeding can be usuallydetermined

rQuestion: Sex of patient?

rSignificance: Hemophilia is X-linked.

rQuestion: Family history of bleeding?

rSignificance: Suggests an inherited bleeding disorder

rQuestion: Bleeding in unusual places withoutsignificant trauma (intracranial, joints)?

rSignificance: May indicate significant factordeficiency—hemophilia

rQuestion: Several surgeries in the past withoutbleeding?

rSignificance: An inherited bleeding disorder is lesslikely

rQuestion: Poorly controlled epistaxis?

rSignificance: Localized trauma (nose-picking) cancause unilateral epistaxis

rQuestion: Purpura or petechiae?

rSignificance: May signify platelet disorders, vonWillebrand disease, or vasculitis

rQuestion: Recent medications?

rSignificance: Aspirin and NSAIDs (e.g., ibuprofen)affect platelet function

rQuestion: Presence of renal or liver disease?

rSignificance:

– Azotemia contributes to bleeding

– Liver disease reduces clotting factors

rQuestion: Severe malnutrition?

rSignificance: May lead to scurvy, vitamin Kdeficiency, or decreased hepatic synthesis ofcoagulation factors

rQuestion: Sudden onset of petechiae?

rSignificance: May indicate idiopathicthrombocytopenia

PHYSICAL EXAM

rFinding: Petechiae in skin and mucous membranes?

rSignificance: Disorder of platelet number orfunction, von Willebrand disease, or vasculitis

rFinding: Small bruises in unusual places?

rSignificance: Possible platelet disorder or vonWillebrand disease

rFinding: Large bruises or palpable bruises?

rSignificance: Coagulation deficiencies, severeplatelet disorders, or von Willebrand disease

rFinding: Delayed wound healing?

rSignificance: Factor XIII deficiency ordysfibrinogenemia

rFinding: Purpura localized to lower body (buttocks,legs, ankles)?

rSignificance: Henoch–Sch ¨onlein purpura

ABNORMAL BLEEDING

A

DIAGNOSTIC TESTS & INTERPRETATION

rTest: Phase 1: Initial laboratory screening

– Definitive platelet testing includes platelet

aggregation and adenosine triphosphate release

studies with ristocetin, collagen, thrombin,

arachidonic acid, and adenosine 5-diphosphate

rSignificance: Qualitative platelet defect suspected

– Factor VIII:C

– Von Willebrand factor antigen (VIIIR:Ag)

– Von Willebrand factor activity (ristocetin cofactor)

– Von Willebrand factor multimeric analysis—only

send after the diagnosis of von Willebrand disease

has been established

– Thrombin time and fibrinogen assay to screen for

afibrinogenemia or dysfibrinogenemia

– Factor XIII deficiency suspected: Factor XIII assay

(urea clot lysis study)

rSignificance: Von Willebrand disease suspected

rTest: Phase 3: Discriminating laboratory studies for

abnormal phase 1 tests

rSignificance:

– When thrombocytopenia is present:

◦ Inspection of blood smear (screening for bone

marrow diseases)

– Mean platelet volume (may be normal or elevated

in destructive causes, elevated in congenital

macrothrombocytopenias, low in Wiskott–Aldrich

syndrome)

– Bone marrow aspiration (rarely necessary)

– When disseminated intravascular coagulopathy is

suspected (infection, liver disease, massive

trauma, PT and aPTT prolonged):

◦ Fibrinogen

◦ D-dimer or fibrin split products

◦ Peripheral smear inspection for RBC fragments

– Prolonged aPTT (inhibitor screen [50:50 mixing

study of patient’s and normal plasma]):

– If aPTT fully corrects with mixing, this is consistent

with a factor deficiency:

◦ Assess for specific factor deficiencies: Factor

VIII, IX, XI, XII

– If partial or no correction after mixing study:

◦ Inhibitor is present

◦ Confirmatory test for the presence of a lupus

anticoagulant with a platelet-neutralizing

bruises on more than one body part

rUncommon sites for bruising for all ages include theback, buttocks, arms, and abdomen

rThe aPTT may be extremely prolonged in patientswith deficiencies of the contact factors (prekallikrein,high molecular weight kininogen [HMWK], factorXII) These deficiencies do not result inbleeding

rImproper specimen collection including heparincontamination or underfilling of the specimen tubecan result in artificially prolonged clotting times

rDo not forget to consider nonaccidental injury as acause of increased bruising

rFactor XII deficiency and lupus anticoagulant are notassociated with abnormal bleeding

ALERT

Pitfalls of testing:

rPFA-100– Low specificity and sensitivity– Affected by medications (NSAIDs)– Not recommended as a screening test

rBleeding time– Prolonged when platelets<100,000/mm3

– Affected by medications such as aspirin,NSAIDs, antihistamines

– Does not correlate well with bleeding risk– Accurate result depends on proper technique

– Not recommended as a screening test

rPT and aPTT– Normal ranges are age dependent

– Polycythemia (hematocrit 65%) or underfilling

of the specimen tube may result in a spuriouslyprolonged result

– Heparin contamination results in a spuriouslyprolonged result

rVon Willebrand disease studies– Values fluctuate over time and may beperiodically normal in affected individuals

– May require repeated testing to make diagnosis

TREATMENT

General Measures

rPressure on wound

rElevation

rTopical application of thrombin

rTopical application of clot-activating polymers

ADDITIONAL READING

rBuchanan GR Bleeding signs in children with

idiopathic thrombocytopenic purpura J Pediatr

Hematol Oncol 2003;25(Suppl 1):S42–S46.

rKhair K, Liesner R Bruising and bleeding in infants

and children: A practical approach Br J Haematol.

2006;133:221–231

rKoreth R, Weinert C, Weisdorf DJ, et al.

Measurement of bleeding severity: A critical review

Transfusion 2004;44:605–617.

rLillicrap D, Nair SC, Srivastava A, et al Laboratory

issues in bleeding disorders Haemophilia 2006;12:

68–75

rManno CS Difficult pediatric diagnoses—bruising

and bleeding Pediatr Clin North Am 1991;

rAfter acute overdose, a serum acetaminophen level

above the treatment line of the Rumack-Matthew

acetaminophen poisoning nomogram should be

considered possibly hepatotoxic

rAcetaminophen is sold under many brand names

and is often an ingredient in combination pain

reliever preparations

rSerious hepatotoxicity after a single acute overdose

by young children is rare compared with that by

adolescents

rMost toddlers with acetaminophen hepatotoxicity

suffer repeated supratherapeutic dosing

EPIDEMIOLOGY

rAnalgesics are the most common drugs implicated

in poisoning exposures among children younger

than 6 years

rAcetaminophen preparations make up∼48% of all

analgesic poisoning exposures reported to poison

control centers

Incidence

In 2003, acetaminophen poisoning was responsible

for 1/2 of all adult cases of acute liver failure

rAcetaminophen should be stored with

child-resistant caps, out of sight of young children

rProper use of acetaminophen products should be

taught to patients with pain or fever

PATHOPHYSIOLOGY

rMost absorbed acetaminophen is metabolized

through formation of hepatic glucuronide and

sulfate conjugates

rSome acetaminophen is metabolized by the

CYP450 mixed-function oxidase system, leading

to the formation of the toxic

– Drug elimination half-life becomes prolonged

– Proportionately more NAPQI is produced

– Glutathione supply cannot meet detoxificationdemand

– Hepatotoxicity or renal toxicity may ensue

ETIOLOGY

rSingle acute overdose of>150 mg/kg or 10 g

rRepeated overdose of>100 mg/kg/d, or 6 g/d, for

>2 days

COMMONLY ASSOCIATED CONDITIONS

rAcetaminophen is often marketed in combinationwith other pharmaceuticals, which may complicate adrug overdose situation

rAdolescents frequently overdose on more than 1drug preparation

DIAGNOSIS

HISTORY

rMedical history of pain or fever:

– Acetaminophen ingestion should be explored inany patient being treated for pain or fever

rAmount of acetaminophen ingested:

– A single, acute ingestion of<150 mg/kg (≤10 g

in adolescents) is unlikely to cause significanttoxicity among otherwise healthy individuals

rSigns and symptoms:

– Initially may be clinically silent– Vomiting

rSerum acetaminophen level:

– Allows application of the Rumack-Matthewnomogram after acute overdose– Rumack-Matthew nomogram applies only tosingle, acute acetaminophen overdose scenarios

rHepatic transaminases:

– Aspartate aminotransferase (AST) is the mostsensitive of the widely available measures toassess acetaminophen hepatotoxicity and begins

to rise 12–24 hours after significant overdose

rLiver and kidney function tests:

– As the AST rises, it is important to follow liver andkidney function with tests such as serum glucose,prothrombin (PT) and partial thromboplastin (PTT)times, serum creatinine, plasma pH, and serumalbumin

– The PT and PTT may be slightly elevated owing todirect effect of elevated blood acetaminophen

concentrations or N-acetylcysteine therapy,

without signifying liver injury

– The decline of an elevated serum AST may indicateeither liver recovery or profound liver failure andmust be interpreted in context

rSingle acute overdose:

– Activated charcoal, 1–2 g/kg (maximum 75 g),may be administered if acetaminophen is judged

to be present in the stomach or proximal intestine(usually within 2 hours of ingestion)

– N-acetylcysteine should be administered if a

serum acetaminophen level obtained>4 hours

after overdose falls above the treatment line ofthe Rumack-Matthew nomogram

– Patients presenting to medical care>7 hours

after overdose should be given a loading dose of

N-acetylcysteine while waiting for the serum

acetaminophen level result