Weinstein Lovell and Winters Pediatric Orthopaedics 7e

L O V E L L A N D W I N T E R ’ S Pediatric Orthopaedics

S E V E N T H E D I T I O N

Pediatric Orthopaedics L O V E L L A N D W I N T E R ’ S S E V E N T H E D I T I O N Volume 1

E d i t o r s Stuart L. Weinstein, MD Ignacio V. Ponseti Chair and Professor of Orthopaedic Surgery Professor of Pediatrics University of Iowa Hospitals and Clinics Iowa City, Iowa John M. (Jack) Flynn, MD Professor of Orthopaedic Surgery University of Pennsylvania Associate Chief of Orthopaedic Surgery The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

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Copyright © 2014 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business Two Commerce Square 2001 Market Street Philadelphia, PA 19103 USA LWW.com All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the above-mentioned copyright. Library of Congress Cataloging-in-Publication Data  Lovell and Winter’s pediatric orthopaedics. — 7th ed. / editors, Stuart L. Weinstein, John M. Flynn.    p. ; cm.  Pediatric orthopaedics  Includes bibliographical references and index.   ISBN 978-1-60547-814-2 (hardback)  I. Lovell, Wood W., 1915- II. Weinstein, Stuart L. III. Flynn, John M.. IV. Title: Pediatric orthopaedics.  [DNLM: 1. Orthopedics. 2. Adolescent. 3. Child. 4. Infant. WS 270]  616.70083—dc23 2012017197 Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the authors, editors, and publisher are not responsible for errors or omis- sions 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 pub- lication. Application of the information in a particular situation remains the professional responsibility of the practitioner. The authors, editors, and publisher have exerted every effort to ensure that drug selection and dos- age set 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 of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug. Some drugs and medical devices presented in the publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings. It is the responsibility of the health care provider to ascertain the FDA status of each drug or device planned for use in their clinical practice. Printed in China

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10 9 8 7 6 5 4 3 2 1

C O N T R I B U T O R S

Michael C. Ain, MD Associate Professor Department of Orthopaedic and Neurosurgery Johns Hopkins Hospital Baltimore, Maryland Benjamin A. Alman, MD, FRCSC Distinguished James R. Urbaniak Professor Chair, Department of Orthopaedic Surgery Duke University Durham, North Carolina Alexandre Arkader, MD Assistant Professor of Clinical Orthopaedic Surgery University of Southern California Keck School of Medicine Director, Bone and Soft Tissue Tumor Program

Michael T. Busch, MD Chief Executive Officer, Children’s Orthopaedics of Atlanta Orthopaedic Surgery Fellowship Director, Children’s Healthcare of Atlanta Surgical Director of Sports Medicine, Children’s Healthcare of Atlanta Atlanta, Georgia

Haemish Crawford, FRACS Pediatric Orthopaedic Surgeon Department of Orthopaedics Starship Children’s Hospital Auckland, New Zealand

Luciano Dias, MD Professor Department of Orthopaedic Surgery Feinberg School of Medicine Northwestern University Attending Physician Department of Pediatric Orthopaedic Surgery Medical Director Motion Analysis Center Children’s Memorial Hospital Chicago, Illinois Matthew B. Dobbs, MD Professor Department of Orthopaedic Surgery Washington University School of Medicine St. Louis Children’s Hospital and Shriners Hospital for Children – St. Louis St. Louis, Missouri John P. Dormans, MD The Richard M. Armstrong Jr. Endowed Chair in Pediatric Orthopaedic Surgery Professor of Orthopaedic Surgery at the University of Pennsylvania School of Medicine Chief of Orthopaedic Surgery The Children’s Hospital of Philadelphia Division of Orthopaedic Surgery Philadelphia, Pennsylvania Amy L. Dunn, MD Associate Professor of Pediatrics Emory University/Children’s Healthcare of Atlanta Aflac Cancer and Blood Disorders Service Atlanta, Georgia

Children’s Orthopaedic Center Children’s Hospital Los Angeles Los Angeles, California

David D. Aronsson, MD Professor Department of Orthopaedics and Rehabilitation and Department of Pediatrics University of Vermont College of Medicine Burlington, Vermont

Donald S. Bae, MD Associate Professor Department of Orthopaedic Surgery Harvard Medical School Associate in Orthopaedic Surgery Department of Orthopaedic Surgery Boston Children’s Hospital Boston, Massachusetts

Frank R. Berenson, MD Pediatric and Adolescent NeuroDevelopmental Associates and Atlanta Headache Specialists Atlanta, Georgia

Richard E. Bowen, MD Clinical Professor

Department of Orthopaedic Surgery Geffen School of Medicine at UCLA Orthopaedic Institute for Children Los Angeles, California

v

vi

CONTRIBUTORS

Georges Y. El-Khoury, MD Professor

H. Kerr Graham, MD, FRCS(Ed), FRACS Professor of Orthopaedic Surgery The University of Melbourne Consultant Orthopaedic Surgeon/Director of Hugh Williamson Gait Analysis Laboratory The Royal Children’s Hospital Murdoch Childrens Research Institute Parkville, Victoria, Australia Matthew A. Halanski, MD Associate Professor, Pediatric Orthopedics Department of Orthopedics and Rehabilitation University of Wisconsin Madison, Wisconsin Drexel University College of Medicine St. Christopher’s Hospital for Children Philadelphia, Pennsylvania Andrew W. Howard, MD, MSc, FRCSC Director, Office of International Surgery Medical Director, Trauma Program Associate Professor Departments of Surgery and Health Policy, Management, and Evaluation University of Toronto The Hospital for Sick Children Toronto, Ontario, Canada Robert M. Kay, MD Professor of Orthopaedic Surgery Keck University of Southern California School of Medicine Vice Chief Martin J. Herman, MD Associate Professor of Orthopaedic Surgery and Pediatrics

Department of Radiology and Orthopaedics University of Iowa Carver College of Medicine Director, Musculoskeletal Section Department of Radiology and Orthopaedics University of Iowa Hospitals and Clinics Iowa City, Iowa John M. Flynn, MD Professor of Orthopaedic Surgery University of Pennsylvania Associate Chief of Orthopaedic Surgery The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Steven Frick, MD Professor Department of Orthopaedic Surgery University of Florida College of Medicine Chair Department of Orthopaedic Surgery Nemours Children’s Hospital Orlando, Florida

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 Mark C. Gebhardt, MD Frederick W. and Jane M. Ilfeld Professor of Orthopaedics Departmeny of Orthopaedic Surgery Harvard Medical School Orthopaedic Surgeon-in-Chief

Children’s Orthopaedic Center Children’s Hospital – Los Angeles Los Angeles, California

Department of Orthopaedic Surgery Beth Israel Deaconess Medical Center Boston, Massachusetts Michael J. Goldberg, MD Director, Skeletal Health Program Chief Skeletal Dysplasia Clinics Orthopaedic Surgeon

Geetika Khanna, MD Associate Professor, Radiology St. Louis Children’s Hospital Mallinckrodt Institute for Radiology Washington University School of Medicine St. Louis, Missouri Young-Jo Kim, MD, PhD Associate Professor Department of Orthopaedic Surgery Harvard Medical School Director Child and Adult Hip Program Boston Children’s Hospital Boston, Massachusetts

Department of Orthopaedics Seattle Children’s Hospital Seattle, Washington

J. Eric Gordon, MD Professor Department of Orthopaedics Washington University in St. Louis

School of Medicine St. Louis, Missouri

vii

CONTRIBUTORS

Mininder S. Kocher, MD, MPH Professor Department of Orthopaedic Surgery Harvard Medical School Associate Director

Yusuf Menda, MD Associate Professor Clinical Director, PET Center Department of Radiology University of Iowa Hospitals and Clinics Iowa City, Iowa José A. Morcuende, MD, PhD Professor Department of Orthopaedic Surgery and Rehabilitation and Department of Pediatrics University of Iowa Iowa City, Iowa

Division of Sports Medicine Children’s Hospital – Boston Boston, Massachusetts

Lawrence G. Lenke, MD Jerome J. Gilden Distinguished Professor of Orthopaedic Surgery Professor of Neurosurgery Chief of Spinal Surgery Department of Orthopaedic Surgery Washington University St. Louis, Missouri

Vincent S. Mosca, MD Professor of Orthopaedics

Department of Orthopaedics and Sports Medicine University of Washington School of Medicine Pediatric Orthopaedic Surgeon Director, Pediatric Orthopaedic Fellowship Seattle Children’s Hospital Seattle, Washington

Jennifer W. Lisle, MD Assistant Professor Department of Orthopaedics and Rehabilitation The University of Vermont College of Medicine Chief, Pediatric Orthopaedics Orthopaedics and Rehabilitation Health Care Service Fletcher Allen Health Care Burlington, Vermont Randall T. Loder, MD George J. Garceau Professor of Orthopaedic Surgery Department of Orthopaedic Surgery Indiana University Director of Pediatric Orthopaedics James Whitcomb Riley Children’s Hospital Indianapolis, Indiana Scott J. Luhmann, MD Associate Professor Department of Orthopaedics Washington University School of Medicine Chief of Spine Surgery Department of Orthopaedics Shriner’s Hospital for Children – St. Louis St. Louis, Missouri James J. McCarthy, MD Associate Professor Department of Orthopaedic Surgery Cincinnati Children’s Hospital Director Department of Orthopaedic Surgery Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio

Peter O. Newton, MD Clinical Professor Department of Orthopaedics

University of California at San Diego Chief of Orthopedics, Medical Practice Foundation Rady Children’s Hospital San Diego, California

Kenneth J. Noonan, MD Chief, Pediatric Orthopaedics University of Wisconsin Madison, Wisconsin

Tom F. Novacheck, MD Adjunct Associate Professor of Orthopaedic Surgery University of Minnesota Director, Jarmes R Gage Center for Gait and Motion Analysis Gillette Children’s Specialty Healthcare St. Paul, Minnesota

Norman Y. Otsuka, MD Joseph E. Milgram Professor Department of Orthopaedic Surgery New York University Director, Center for Children NYU Langone Hospital for Joint Diseases New York, New York

viii

CONTRIBUTORS

Alexander K. Powers, MD Assistant Professor Department of Neurosurgery, Orthopaedics, and Pediatrics Wake Forest University School of Medicine Winston-Salem, North Carolina Margaret M. Rich, MD Orthopaedic Surgeon Shriners Hospital for Children – St. Louis St. Louis, Missouri James O. Sanders, MD Professor of Orthopaedics and Pediatrics Department of Orthopaedics and Rehabilitation University of Rochester Chief, Division of Pediatrics Golisano Children’s Hospital at Strong Rochester, New York Jeffrey R. Sawyer, MD Associate Professor Department of Orthopaedic Surgery University of Tennessee Campbell Clinic Le Bonheur Children’s Hospital Memphis, Tennessee Perry L. Schoenecker, MD Professor Department of Orthopaedic Surgery Chief Department of Pediatric Orthopaedics Shriners Hospital for Children – St. Louis St. Louis, Missouri Suken A. Shah, MD Division Chief, Spine and Scoliosis Service Clinical Fellowship Director Attending Pediatric Orthopaedic Surgeon Nemours/Alfred I. duPont Hospital for Children Wilmington, Delaware Associate Professor

Kit Song, MD, MHA Clinical Professor Department of Orthopedic Surgery UCLA School of Medicine Chief of Staff Shriners Hospitals for Children – Los Angeles Los Angeles, California David L. Skaggs, MD, MMM Professor and Chief of Orthopaedic Surgery Children’s Hospital Los Angeles

University of Southern California Keck School of Medicine Children’s Hospital Chair of Pediatric Spinal Disorders Los Angeles, California Paul D. Sponseller, MD, MBA Sponseller Professor and Head, Pediatric Orthopaedics Johns Hopkins Bloomberg Children’s Center Baltimore, Maryland

Anthony A. Stans, MD Consultant Department of Orthopaedic Surgery Mayo Clinic Rochester, Minnesota Vineeta T. Swaroop, MD Instructor of Orthopaedic Surgery Northwestern University

Feinberg School of Medicine Children’s Memorial Hospital Chicago, Illinois

Pam Thomason, BPhty, M Physio Senior Physiotherapist and Manager

Hugh Williamson Gait Analysis Laboratory The Royal Children’s Hospital – Melbourne Parkville, Victoria, Australia George H. Thompson, MD Professor of Orthopaedic Surgery and Pediatrics Case Western Reserve University Director, Pediatric Orthopaedics Rainbow Babies & Children’s Hospital Vice-Chairman, Department of Orthopaedics University Hospitals Case Medical Center Cleveland, Ohio

Department of Orthopaedic Surgery Jefferson Medical College of Thomas Jefferson University Philadelphia, Pennsylvania Ernest L. Sink, MD Associate Professor Department of Orthopaedic Surgery

William C. Warner Jr, MD Professor of Orthopaedics Department of Orthopaedic Surgery University of Tennessee Campbell Clinic Le Bonheur Children’s Hospital Memphis, Tennessee

Weil Cornell Medical School Hospital for Special surgery New York, New York

ix

CONTRIBUTORS

Peter M. Waters, MD Orthopedic Surgeon in Chief Children’s Hospital Boston John E. Hall Professor of Orthopaedic Surgery Harvard Medical School Boston, Massachusetts Stuart L. Weinstein, MD Ignacio V. Ponseti Chair and Professor of Orthopaedic Surgery Professor of Pediatrics University of Iowa Hospitals and Clinics Iowa City, Iowa Pamela F. Weiss, MD, MSCE Attending Physician Division of Rheumatology Children’s Hospital of Philadelphia Assistant Professor

Dennis R. Wenger, MD Clinical Professor

Department of Orthopaedic Surgery University of California San Diego Director, Pediatric Orthopedic Training Program Rady Children’s Hospital San Diego San Diego, California

R. Baxter Willis, MD Head, Department of Surgery

Children’s Hospital of Eastern Ontario Professor of Surgery (Orthopaedics) University of Ottawa Ottawa, Ontario, Canada Burt Yaszay, MD Assistant Clinical Professor Department of Orthopaedics University of California at San Diego Orthopaedic Surgeon Rady Children’s Hospital San Diego, California

Department of Pediatrics University of Pennsylvania Philadelphia, Pennsylvania

P r e f a c e

his seventh edition of Pediatric Orthopaedics repre- sents a complete renovation and reorganization of the central textbook of pediatric orthopaedics. The editors and publishers have worked to incorporate into the main textbook the atlas material (which in the past stood as a separate volume) so that the surgeon can move seamlessly from background and indications to surgical technique and outcomes. The science of pediatric orthopaedics has now been married to its art, to create a comprehensive source for those who care for children and adolescents with musculoskeletal problems and injuries. Incorporating the atlas has been an immense task, relying on the hard work and patience of many: authors, editors, the artist, and production personnel. We are gratified to see that the final product accomplished our vision to meet the needs of the modern pediatric orthopaedist. Since the last edition, the field of pediatric orthopaedics has moved forward at a rapid pace and grown substantially in the number of orthopaedists who make caring for chil- dren the central part of their practice. Basic science work in molecular biology, genetics, and embryology continues to inform our understanding of etiology, but there is still much mystery and very little therapeutic intervention at this time. There have been innumerable advances and changes in stan- dard of care in many areas in the last few years: clubfoot, hip dysplasia, limb deformity, slipped capital femoral epiphysis, pediatric sports medicine, spinal deformity, musculoskel- etal oncology and infection, and upper extremity disorders. Meanwhile, trauma care has become more operative, achieving better results with more rapid mobilization. One clear trend in T

pediatric ­orthopaedics is subspecialization. To give readers the most evidence-based and cutting-edge information, we have enlisted the expertise of a large number of new authorities in many different pediatric orthopaedic subspecialties. We have asked these experts to synthesize the literature, provide the best indications for surgery, describe the best procedures in careful detail, and warn the reader about potential pitfalls in care. One unique strength that sets this pediatric orthopaedic textbook apart is the tremendous diversity of expertise from around the world. The authors of this edition hail from 28 dif- ferent centers of excellence and several countries from around the world. By inviting such a wide range of authors from so many different institutions, we have avoided a narrow, paro- chial approach to solving orthopaedic problems for children. In many cases, the chapters are coauthored by experts from different centers, so that each can critique the other when nec- essary. We live in an age where parents can learn more about a condition in twenty minutes on the Internet than most clini- cians could learn years ago sorting through textbooks and jour- nals for hours. We also live in an age where families and payers are demanding increased attention to quality and value. In this seventh edition of Pediatric Orthopedics , we have worked to assemble a single source of information so the pediatric ortho- paedist can deliver the highest quality and highest value care and satisfy the information needs of the most informed and sophisticated families they encounter.

SLW and JMF

xi

A c k n o w l e d g m e n t s

he editors would like to acknowledge the hard work and dedication of the authors, the skill of our medi- cal illustrator, and the commitment of our publisher to complete this important project. Stuart Weinstein would like to thank his wife Lynn and son Will for their support and encouragement over the years and his former collaborator Ray Morrissy for his guidance and T

inspiration on previous editions of Pediatric Orthopaedics and most importantly his friendship. Jack Flynn would like to acknowledge the patience and understanding of his wife Mary and children Erin, Colleen, John, and Kelly as he dedicated many hours to the project. They understand that Dad has homework too.

xiii

C O N T E N T S

Contributors v Preface xi Acknowledgments xiii

13 Bone and Soft-Tissue Tumors

426

Alexandre Arkader, Mark C. Gebhardt, and John P. Dormans

14 Cerebral Palsy

Volume 1 1 Embryology and Development of the Neuromuscular Apparatus José A. Morcuende and James O. Sanders 2 Genetic Aspects of Orthopaedic Conditions José A. Morcuende and Benjamin A. Alman 3 Imaging in Pediatric Orthopaedics

484

H. Kerr Graham, Pam Thomason, and Tom F. Novacheck

15 Myelomeningocele

1

555

Vineeta T. Swaroop and Luciano Dias 16 Other Neuromuscular Disorders George H. Thompson and Frank R. Berenson

587

41

17 Idiopathic Scoliosis 18 Congenital Scoliosis Suken A. Shah and Kit Song

629

56

Peter O. Newton, Dennis R. Wenger, and Burt Yaszay

Geetika Khanna, Georges Y. El-Khoury, and Yusuf Menda

4 The Pediatric Orthopaedic Examination

698

87

19 Kyphosis

David D. Aronsson and Jennifer W. Lisle 5 Evaluation of the Medical Literature 129 Mininder S. Kocher 6 Metabolic and Endocrine Abnormalities 140 Andrew W. Howard and Benjamin A. Alman 7 The Skeletal Dysplasias 177 Paul D. Sponseller and Michael C. Ain 8 Syndromes of Orthopaedic Importance 218 Benjamin A. Alman and Michael J. Goldberg 9 Localized Disorders of Skin and Soft Tissue 278 Haemish Crawford 10 Diseases of the Hematopoietic System 319 Michael T. Busch and Amy L. Dunn 11 Juvenile Idiopathic Arthritis 348 Pamela F. Weiss 12 Musculoskeletal Infection 369 Anthony A. Stans

739

William C. Warner Jr and Jeffrey R. Sawyer 20 Spondylolysis and Spondylolisthesis

791

Alexander K. Powers, Lawrence G. Lenke, and Scott J. Luhmann

21 The Cervical Spine

821

Randall T. Loder

Index I-1

Volume 2 22 The Upper Limb

895

Donald S. Bae and Peter M. Waters 23 Developmental Hip Dysplasia and Dislocation Stuart L. Weinstein 24 Legg-Calvé-Perthes Syndrome Stuart L. Weinstein 25 Slipped Capital Femoral Epiphysis

983

1112

1165

Robert M. Kay and Young-Jo Kim

xv

xvi

CONTENTS

26 Other Conditions of the Hip Matthew B. Dobbs and José A. Morcuende 27 The Lower Extremity 28 Limb-Length Discrepancy Matthew A. Halanski and Kenneth J. Noonan

32 The Principles of Pediatric Fracture and Trauma Care Martin J. Herman and James J. McCarthy 33 Upper Extremity Fractures in Children David L. Skaggs and Steven Frick 34 Thoracolumbar Spine and Lower Extremity Fractures

1222

1661

1261

Perry L. Schoenecker, Margaret M. Rich, and J. Eric Gordon

1694

1341

29 The Foot

1773

1388

Ernest L. Sink and John M. Flynn

Vincent S. Mosca 30 The Child with a Limb Deficiency 1526 Richard E. Bowen and Norman Y. Otsuka 31 Sports Medicine in the Growing Child 1596 R. Baxter Willis, Mininder S. Kocher, and Theodore J. Ganley

Index I-1

L O V E L L A N D W I N T E R ’ S Pediatric Orthopaedics

S E V E N T H E D I T I O N

C H A P T E R 11 Juvenile Idiopathic Arthritis

Pamela F. Weiss

OVERVIEW OF PEDIATRIC RHEUMATIC DISEASE ENCOUNTERED BY THE PEDIATRIC ORTHOPAEDIC SURGEON Joint pain is a common childhood complaint. Each year, as many as 1% of all children will be evaluated by a physician for joint pain (1). Approximately 15% of healthy children reported on a health questionnaire that they had episodes of musculoskeletal pain (2). Further, healthy children in day care centers have approximately one painful episode every 3 hours, arising from play, disciplining, or interaction with peers (3). The orthopaedic surgeon is often the first specialist to encoun- ter the child with joint, limb, or back pain. In a study of subspecialty referrals of juvenile arthritis, most children with pauciarticular juvenile rheumatoid arthritis (JRA) (62%) were referred to orthopaedic surgeons prior to referral to pediatric rheumatology care (4). Among children who are evaluated by a physician for pain in the joints, only 1 in 100 will eventually be diagnosed as having arthritis, but among those who present to an orthopaedist, the frequency of arthritis is surely higher. Accordingly, it is important that the orthopaedic surgeon be able to identify the most likely cause of the pain and either initiate treatment or refer the patient to an appropriate medi- cal specialist. The purpose of this chapter is to provide the orthopae- dic surgeon with an in-depth understanding of the presenta- tion, differential diagnosis, and management of children with arthritis. With this framework, the orthopaedic specialist should be able to identify children with juvenile arthritis and to differentiate arthritis from benign pains of childhood, psy- chogenic pain syndromes, benign musculoskeletal back pain, infection, malignancy, or other systemic autoimmune diseases (lupus, dermatomyositis, and vasculitis). Infectious, malig- nant, congenital, mechanical, or traumatic causes of arthralgias and arthritis are presented in order to contrast the symptoms with those of juvenile arthritis; detailed presentations on these conditions can be found elsewhere in this text.

CLASSIFICATION OF JUVENILE ARTHRITIS Juvenile arthritis is a term for persistent arthritis lasting > 6 weeks of unclear etiology. A diagnosis of juvenile arthritis is made by taking a thorough history, performing a skilled and comprehensive physical examination, utilizing directed labo- ratory tests and imaging procedures, and following the child over time. Over the past several decades, there have been three sets of criteria utilized for the diagnosis and classification of juve- nile arthritis (Table 11-1). The first set of criteria was pro- posed in 1972 by the American College of Rheumatology (ACR) and defined three major categories of JRA: oligoar- ticular (pauciarticular), polyarticular, and systemic (5).The ACR JRA criteria exclude other causes of juvenile arthritis, such as spondyloarthropathies [JAS, inflammatory bowel dis- ease (IBD)-associated arthritis, and related diseases], juvenile psoriatic arthritis, arthritis associated with other systemic inflammatory diseases [systemic lupus erythematosus (SLE), dermatomyositis, sarcoidosis, etc.], and infectious or neo- plastic disorders. The second set of criteria was formulated in 1977 by the European League Against Rheumatism (EULAR) and coined the term juvenile chronic arthritis (JCA) (6). JCA is differentiated into the following subtypes: pauciarticular, polyarticular, juvenile rheumatoid [positive rheumatoid fac- tor (RF)], systemic, juvenile ankylosing spondylitis (JAS), and juvenile psoriatic arthritis. The ACR and EULAR crite- ria, although similar, do not identify identical populations or spectra of disease. However, they have often been used inter- changeably, leading to confusion in the interpretation of stud- ies relating to the epidemiology, treatment, and outcome of juvenile arthritis. In 1993, The International League of Associations of Rheumatologists (ILAR) proposed (7) and revised (8) crite- ria for the diagnosis and classification of juvenile arthritis (Table 11-2). The term juvenile idiopathic arthritis (JIA) has been proposed as a replacement for both JRA and JCA. The

348

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CHAPTER 11  |  Juvenile Idiopathic Arthritis

Comparison of JRA, JCA, and JIA Classifications

TABLE 11-1

JRA

JCA

JIA

Committee Age at onset

ACR

EULAR < 16 yr > 3 mo

ILAR

< 16 yr > 6 wk

< 16 yr > 6 wk

Disease duration

Onset types

Pauciarticular Polyarticular Systemic

Pauciarticular Polyarticular RF-negative Juvenile rheumatoid arthritis Systemic Juvenile psoriatic arthritis Juvenile ankylosing spondylitis

Oligoarticular, persistent Oligoarticular, extended Polyarticular RF-negative Polyarticular RF-positive Systemic Psoriatic arthritis Enthesitis-related arthritis

Exclusions

Juvenile psoriatic arthritis Juvenile ankylosing spondylitis Inflammatory bowel disease Other forms of juvenile ­arthritis

Other forms of juvenile arthritis

Other forms of juvenile arthritis

RF, rheumatoid factor.

Criteria for Classification of JIA

TABLE 11-2

Exclusions a

Inclusion Criteria b

JIA Subtype Oligoarthritis  Persistent  Extended

1–5

≤ 4 joints during disease course > 4 joints after the first 6 mo

Arthritis affecting ≥ 5 joints during the first 6 mo Arthritis affecting ≥ 5 joints during the first 6 mo, plus RF positivity on two occasions more than 3 mo apart

Polyarthritis RF-negative Polyarthritis RF-positive

1–5

1–3, 5

Systemic

1–4

Arthritis with or preceded by daily fever of at least 2 weeks’ duration, accompanied by one or more of the following:  Evanescent, nonfixed erythematous rash  Generalized adenopathy  Hepatomegaly or splenomegaly  Serositis Arthritis and psoriasis, or arthritis and at least two of the following: a. Dactylitis b. Nail abnormalities (pitting or onycholysis) c. Family history of psoriasis in a first-degree relative Arthritis and enthesitis, or arthritis or enthesitis with at least two of the following: 1. SI joint tenderness and/or inflammatory spinal pain 2. Presence of HLA-B27 3. Family history of HLA-B27–associated disease in a first-degree ­relative 4. Onset of arthritis in a male after the age of 6 yr Children with arthritis of unknown cause that persists ≥ 6 wk Does not fulfill criteria for any of the other categories Fulfills criteria for ≥ 1 of the other categories

Psoriatic

2–5

Enthesitis-related

1, 4, 5

Undifferentiated

a Exclusions: 1, psoriasis in the patient or a first-degree relative; 2, arthritis in an HLA-B27 positive male beginning after the sixth birthday; 3, ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with IBD, Reiter syndrome, or acute anterior uveitis in a ­first-degree relative; 4, IgM RF on at least two occasions more than 3 mo apart; 5, presence of systemic JIA. b Inclusion criteria for all subtypes: 1, age at onset < 16 yr; 2, arthritis in one or more joints; 3, duration of disease is at least 6 wk. From Petty RE, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31(2):390–392.

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CHAPTER 11  |  Juvenile Idiopathic Arthritis

ILAR criteria allow for uniform interpretation of clinical and therapeutic data. Recent validation of the ILAR classification criteria has found that 80% to 88% of children could be clas- sified, and 12% to 20% were classified as “Undifferentiated” because they either did not fit into any category or fulfilled the criteria under two categories (9–12). As genetic risk factors and specific triggers of juvenile arthritis are identified, modifi- cations to the criteria can be made. In the remaining sections of this chapter, the emphasis will be on the JIA classification scheme. The terms JRA and JCA will be used only when refer- ring to specific epidemiologic, therapeutic, or outcome data. Oligoarthritis Definition.  Oligoarthritis is the most common subtype of JIA and is defined by arthritis in four or fewer joints during the first 6 months of disease. Oligoarticular JIA is further divided into persistent and extended course. Persistent oligoarthritis affects a maximum of four joints throughout the disease course. Extended oligoarthritis affects a total of more than four joints after the first 6 months of disease. Exclusions to a diagnosis of oligoarticular JIA include the following: (a) psoriasis or a his- tory of psoriasis in a first-degree relative; (b) arthritis in a first- degree relative after the age of 6 years; (c) ankylosing spondylitis (AS), enthesitis-related arthritis sacroiliitis with IBD, reactive arthritis, or acute anterior uveitis, or a history of one of these in a first-degree relative; (d) presence of IgM RF on at least two occasions, measured 3 months apart; and (e) systemic JIA (8). Epidemiology.  Most children with oligoarthritis present before 4 years of age and girls outnumber boys by a ratio of 4 to 1. Whites are affected more often than other races. It is the most frequent subtype of JIA, accounting for up to 40% of cases (13, 14). Prevalence is estimated at 60 per 100,000 children (15). Etiology.  The etiology of oligoarticular JIA is unknown, but associations with HLA-A2, DRB1*01, DRB1*08, DRB1*11, DRB1*13, DPB1*02, DQA1*04, and DQB1*04 have been reported (14, 16). Oligoarticular JIA is rarely familial. Approximately 70% of oligoarticular JIA patients are positive for antinuclear antibodies (ANA). Clinical Features.  Approximately 50% of children with oligoarticular JIA present with a single affected joint, most commonly the knee, followed by ankles and small joints of the hands. The hips and shoulders are rarely affected. Early wrist involvement is uncommon and may portend progression to a polyarticular or extended oligoarticular course. At presenta- tion, the majority of children have morning stiffness, gelling, and pain. However, up to 25% of children have painless arthri- tis at presentation (17). Most children with oligoarticular JIA have a mild and remitting course. However, in untreated children with long- standing unilateral knee arthritis, there can be overgrowth of the affected limb, resulting in a marked leg-length discrepancy (18, 19). Temporomandibular joint (TMJ) arthritis is present

in a majority of children at disease onset (20) and if untreated, may cause localized growth disturbances, micrognathia, mal- occlusion, and chewing difficulties (21–23). Chronic uveitis is the most common extra-articular complication seen in oli- goarthritis, is associated with ANA positivity, and occurs in approximately 20% of children. Periodic screening for uveitis is necessary as the inflammation is typically asymptomatic and unable to be detected without the use of a slit lamp. Untreated uveitis may result in cataracts, band keratopathy, secondary glaucoma, and blindness. Long-term, children with oligoarticular JIA have the great- est likelihood of remission of all JIA subtypes. In one study, 68% of persistent and 31% of extended oligoarticular JIA patients achieved long-term clinical remission off medication (24). Polyarticular Arthritis Definition.  Polyarticular JIA is defined by arthritis in five or more joints during the first 6 months of disease. Polyarticular JIA is further divided into RF-positive and -negative disease. RF positivity is defined as the presence of IgM RF on at least two occasions, measured at least 3 months apart. Exclusions to a diagnosis of polyarticular JIA include the following: (a) psoriasis or a history of psoriasis in a first-degree relative; (b) arthritis in a first-degree relative after the age of 6 years; (c) AS, enthesitis- related arthritis sacroiliitis with IBD, reactive arthritis, or acute anterior uveitis; (d) or a history of one of these in a first-degree relative; and (e) systemic JIA (8). Epidemiology.  RF-negative polyarthritis can occur at any age, with the median age of onset at 6.5 years (25), with girls outnumbering boys by a ratio of 3:1. RF-positive poly- articular JIA occurs most frequently in adolescent girls and is ­indistinguishable from adult rheumatoid arthritis (RA). Polyarticular JIA is the second most frequent subtype of JIA, accounting for up to 22% of cases (13, 14). Prevalence is esti- mated at 40 and 10 per 100,000 children for RF-negative and RF-positive subtypes, respectively (15). Etiology.  The etiology of polyarticular JIA is unknown. Multiple studies have examined the association of HLA genes and disease. RF-negative polyarticular JIA has been associ- ated with HLA-A2, DRB1*08, DQA1*04, and DPB1*03. Associations of RF-positive polyarticular JIA with HLA- DQA1*03, DQB1*03, and DRB1*04, a gene also associated with adult RA, have been reported (14). Clinical Features.  Polyarticular-onset JIA is character- ized by the insidious, but occasionally acute, onset of sym- metric arthritis in five or more joints. It can involve both large and small joints and frequently affects the cervical spine and TMJs. Mild systemic features such as low-grade fever, lymphadenopathy, and hepatosplenomegaly may be present at diagnosis. The fevers are not typically the high quotidian temperature spikes that are diagnostic of systemic arthritis, and rash is rarely seen (26).

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This RF-negative subgroup may be ANA positive (40% to 50%), and this is associated with an increased incidence of uveitis (5%) (27). Children with RF-positive polyarticular JIA are more likely to have a symmetric small-joint arthritis, rheumatoid nodules, and early erosive synovitis with a chronic course. However, these children rarely develop chronic uveitis. Children with RF-positive polyarticular JIA are at risk for a prolonged and destructive course. These children are typi- cally older girls with involvement of multiple joints (20 or more) including the small joints of the hands and feet, early erosions, and rheumatoid nodules. The presence of hip arthri- tis has been shown to be a poor prognostic sign and may lead to destruction of the femoral heads (28). If polyarthritis per- sists longer than 7 years, remission is unlikely. In a recent study, only 5% of RF-positive and 30% of RF-negative polyarticular JIA patients achieved long-term remission off medication (24). Systemic Arthritis Definition.  Systemic-onset juvenile arthritis (29) was first completely described by Still in 1897, and is therefore often referred to as Still disease . Systemic JIA is defined by arthritis in at least one joint, fever of at least 2 weeks’ duration that is docu- mented to be quotidian for at least 3 days, and at least one of the following: (a) evanescent and erythematosus rash (Fig. 11-1); (b) generalized lymphadenopathy; (c) hepatosplenomegaly; and (d) serositis. Exclusions to a diagnosis of systemic JIA include

the following: (a) psoriasis or a history of psoriasis in a first- degree relative; (b) arthritis in a first-degree relative after the age of 6 years; (c) AS, enthesitis-related arthritis sacroiliitis with IBD, reactive arthritis, or acute anterior uveitis, or a history of one of these in a first-degree relative; and (d) presence of IgM RF on at least two occasions, measured 3 months apart (8). Epidemiology.  Systemic JIA is one of the least common JIA subtypes, accounting for approximately 10% of all JIA cases (13). Onset can occur at anytime during childhood but peaks between 1 and 5 years of age (25). Boys and girls are affected equally. Prevalence of systemic JIA is estimated at 10 per 10,000 children (15). Etiology.  Etiology of systemic JIA is unknown. HLA asso- ciations that have been reported include DRB1*04, DRB1*11, and DQA1*05 (14). Non-HLA genetic associations have been found with macrophage migration inhibitory factor (30) and a variant of the interleukin-6 (IL-6) gene (8). Clinical Features.  The fever of systemic JIA is typically daily or twice-daily, usually to 39°C or higher (31). In between fever spikes, the temperature is often below normal. Children frequently appear quite ill while febrile but recover in between fevers. The fever often responds poorly to nonsteroidal anti- inflammatory drugs (NSAIDs) but will typically respond well to corticosteroids. In most children, the fever is accompanied by a characteristic rash that consists of discrete, transient, non- pruritic erythematous macules (Fig. 11-2) (32). The rash is typically more pronounced on the trunk but may occur on the extremities and the face. The most commonly involved joints are the knee, wrist, and ankle (33). Many children with systemic JIA will have extra-articular manifestations, including hepatosplenomegaly, pericarditis, pleuritis, lymphadenopathy, and abdominal pain. The extra-articular features may be pres- ent for weeks, months, and, occasionally, years prior to the onset of arthritis. Usually, the extra-articular manifestations of systemic JIA are self-limiting and will resolve spontaneously or with corticosteroid therapy. Occasionally, the pericarditis can result in tamponade. The prognosis of systemic JIA is determined predomi- nantly by the course of arthritis. Approximately 50% of children with systemic arthritis will have a mild oligoarticu- lar course, and in most of these children, the arthritis will ultimately remit. The remaining half of the children with systemic onset will develop a polyarticular arthritis that can remit, but progresses in approximately 50% of the cases (25% of all systemic-onset JIA) to a severe, unrelenting, and destructive course despite all currently available therapeutic interventions (34). Chronic anterior uveitis is extremely rare in systemic arthritis. Systemic amyloidosis, usually presenting with the onset of proteinuria and hypertension, can occur as a result of any chronic inflammatory disease. Approximately 8% of European children with systemic JIA have been shown to develop this life-threatening complication (35). The inci- dence of amyloidosis in North America is significantly lower

Figure 11-1.  Rash associated with systemic-onset juvenile ­idiopathic arthritis.

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CHAPTER 11  |  Juvenile Idiopathic Arthritis

A B Figure 11-2.  Juvenile psoriatic arthritis. A: Nail pitting associated with psoriasis. B: Swelling of a single DIP joint in a child with juvenile psoriatic arthritis.

Etiology.  The etiology of psoriatic arthritis is unknown but genetic associations with HLA-Cw6, DRB1*01, and DQA1*0101 have been demonstrated (14, 43). There is often a strong family history of psoriasis or psoriatic arthritis in affected children. Clinical Features.  The arthritis in psoriatic JIA is often an asymmetric mono- or polyarthritis affecting both large and small joints. At onset, patients may have pitting of the nails (67%) (Fig. 11-2) and a family history of psoriasis (69%) or dactylitis (39%), while less than one-half of the children have the rash of psoriasis (13% to 43%) (25, 44, 45). JIA criteria do not require the development of psoriasis to confirm a diagnosis of psoriatic arthritis (Table 11-2) (46). In children younger than 5 years, the presentation is often characterized by the ­involvement of a small number of fingers or toes that are relatively asymptomatic, but leading to marked overgrowth of the digit(s). Children with psoriatic arthritis may have chronic life- long arthritis that follows a relapsing and remitting course. Arthritis mutilans and severe distal interphalangeal (DIP) joint disease are unusual. However, many of the children will have prolonged polyarthritis that may result in irreversible joint damage (47). Amyloidosis has been reported in the European literature as having resulted in the deaths of at least three chil- dren (47, 48). Chronic anterior uveitis has been observed in up to 17% of the children (44, 45) and is associated with a positive ANA titer; the uveitis associated with psoriatic JIA is clinically indistinguishable from the uveitis in oligoarticular and polyarticular JIA. Enthesitis-Related Arthritis Definition.  The JIA criteria for classification of ERA describe a group of arthritides that includes undifferentiated spondyloarthritis, JAS, and IBD-associated arthritis. The JIA criteria include many of the children who were previously diagnosed with a syndrome of seronegativity, enthesopathy,

than that seen in Europe. The reason for this discrepancy remains unclear. Macrophage activation syndrome (MAS), also termed hemophagocytic lymphohistiocytosis , is a severe, potentially life- threatening complication seen nearly exclusively in systemic arthritis. It is characterized by macrophage activation with hemophagocytosis and is associated with hepatic dysfunc- tion, disseminated intravascular coagulation with a precipitous fall in the erythrocyte sedimentation rate (ESR) secondary to hypofibrinogenemia, and encephalopathy (36). It has been suggested that anti-inflammatory medications and viral infec- tions can induce this syndrome. High-dose corticosteroids, cyclosporine A, and IL-1 inhibition have been shown to improve the ­outcome of MAS (37–39). Psoriatic Arthritis Definition.  Psoriatic arthritis is defined as the presence of arthritis and psoriasis, or arthritis and at least two of the fol- lowing: (a) dactylitis, (b) nail pitting or onycholysis (Fig. 11-2), and (c) psoriasis in a first-degree relative. Exclusions to a diag- nosis of psoriatic JIA include the following: (a) arthritis in a first-degree relative after the age of 6 years; (b) AS, enthesitis- related arthritis sacroiliitis with IBD, reactive arthritis, or acute anterior uveitis, or a history of one of these in a first-degree relative; (c) presence of IgM RF on at least two occasions, mea- sured 3 months apart; and (d) systemic JIA (8). Epidemiology.  Psoriasis occurs in approximately 0.5% of the population (40), 20% to 30% of whom have associated arthritis (41, 42). There is a bimodal distribution of age of onset with a peak in the preschool years and again around 10 years of age. Girls are slightly more affected than boys. Psoriasis often begins after the onset of arthritis, usually within 2 years. The prevalence of psoriatic JIA is estimated at 15 per 100,000 children (15). Psoriatic arthritis accounts for 5% to 7% of JIA (13).

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plantar fascia insertion into the metatarsal heads. One study suggested that “pathologic” enthesitis be defined as the pres- ence of three tender entheses at the following sites: SI joints, inferior patellar pole, Achilles tendon insertion, and plantar fascia insertion into the calcaneus (52). The primary extra-articular manifestation of ERA is acute anterior uveitis, which can occur in up to 27% of children with AS (53). The uveitis is manifested by an acute, painful, red, photophobic eye. ERA-associated uveitis may resolve with no ocular residua, but some of the children will have a persis- tent uveitis that is relatively resistant to therapy and can result in blindness (54, 55). Juvenile Ankylosing Spondylitis Definition.  The definition of ERA overlaps with that of spon- dyloarthropathies, a group of conditions that includes JAS and reactive arthritis. Radiographic evidence of bilateral sacroiliitis is necessary to fulfill the New York criteria for AS (Table 11-3). Epidemiology.  JAS most often presents in late childhood or adolescence. Boys outnumber girls by a ratio of 6 to 1 (56). There is a high frequency of JAS in Pacific Canada Indians (57) and a low incidence in African Americans (58). Etiology.  The similarities between JAS and reactive arthritis, in which gastrointestinal and genitourinary infections trigger disease, suggest a role for infection. There is a strong genetic component to disease as AS occurs up to 16 times more fre- quently in HLA-B27–positive family members of patients with AS than in HLA-B27–positive individuals in the population at large (59). Further, children with JAS and SI involvement are frequently HLA-B27 positive (82% to 95%) (56). Clinical Course.  Children with early JAS often fulfill the diagnostic criteria for ERA. Episodic arthritis of the lower extremity large joints, enthesitis, and tarsitis within 1 year of symptom onset predicts of progression to JAS (60). The pre- sentation of JAS is most remarkable for the absence of axial involvement. Only 12% to 24% of children with JAS have pain, stiffness, or limitation of motion of the SI or lumbosacral spine at disease onset. A peripheral arthropathy or ­enthesopathy, Clinical criteria Limited lumbar motion in all three planes History or presence of lumbar spinal pain ≤ 2.5 cm of chest expansion at the 4th intercostal space Definite AS Grade 3 or 4 bilateral radiographic SI changes plus at least 1 clinical criterion Grade 3 or 4 unilateral or grade 2 bilateral ­radiographic SI changes plus clinical criterion 1 or criteria 2 and 3 Probable AS Grade 3 or 4 bilateral radiographic SI changes without any clinical criteria TABLE 11-3 New York Criteria for AS

and arthropathy (SEA syndrome) who were shown to be at increased risk for development of classic spondyloarthritis or JAS (49, 50). ERA is defined as arthritis and enthesitis or arthritis or enthesitis with at least two of the following: (a) the presence or a history of sacroiliac (SI) tenderness or lumbosa- cral pain; (b) HLA-B27 antigen positivity; (c) onset of arthritis in a male after age of 6 years; (d) acute anterior uveitis; and (e) history of AS, ERA, sacroiliitis with IBD, reactive arthritis, or acute anterior uveitis in a first-degree relative. Exclusions for a diagnosis of ERA include (a) psoriasis or a history of psoriasis in the patient or a first-degree relative; (b) presence of IgM RF on at least two occasions, measured 3 months apart; and (c) systemic JIA. Epidemiology.  Unlike the other subtypes of JIA, ERA is more common in boys. Disease onset is typically after the age of 6 years. Prevalence is estimated at 50 per 100,000 children (15). Etiology.  The presence of HLA-B27 is part of the diag- nostic criteria for ERA. In these children, molecular mimicry is thought to contribute to the pathogenesis. Other HLA genetic associations that have been found are HLA-DRB1*01, DQA1*0101, and DQB1*05 (14). Clinical Features.  ERA is often associated with enthesi- tis and arthralgias or arthritis long before any axial skeletal involvement is identified (50). Enthesitis is identified when marked tenderness is noted at the 6, 10, and 2 o’clock posi- tions on the patella, at the tibial tuberosity, iliac crest, or the attachments of the Achilles tendon or plantar fascia (Fig. 11-3) (51). However, in ERA not all entheses are created equal; some entheses are more prone to trauma and mechanical damage such as in Sinding-Larsen-Johansson syndrome while other entheses are frequently tender in normal children such as the

Figure 11-3.  Achilles tendonitis and enthesitis in a child with enthesitis-related arthritis. (Courtesy of Dr. Ruben Burgos-Vargas.)