Primer on the

Rheumatic Diseases
THIRTEENTH EDITION
Primer on the
Rheumatic Diseases
THIRTEENTH EDITION

Edited by

John H. Klippel, MD
John H. Stone, MD, MPH
Leslie J. Crofford, MD
Patience H. White, MD, MA
John H. Klippel, MD John H. Stone, MD, MPH
President and CEO Associate Physician
Arthritis Foundation Massachusetts General Hospital
Atlanta, GA, USA Deputy Editor for Rheumatology
UpToDate
Leslie J. Crofford, MD Boston, MA, USA
Gloria W. Singletary Professor of
Internal Medicine Patience H. White, MD, MA
Chief, Division of Rheumatology & Chief Public Health Officer
Women’s Health Arthritis Foundation
University of Kentucky Atlanta, GA, USA
Lexington, KY, USA

Library of Congress Control Number: 2007925709

ISBN: 978-0-387-35664-8 e-ISBN: 978-0-387-68566-3

Printed on acid-free paper

© Springer Science+Business Media, LLC. 2008

All rights reserved. This work may not be translated or copied in whole or in part without the written
permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York,
NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in
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going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility
for any errors or omissions that may be made. The publisher makes no warranty, express or implied,
with respect to the material contained herein.

9 8 7 6 5 4 3 2 1

springer.com
 FOREWORD

The 13th edition of the Primer on the Rheumatic Diseases is an extraordinary hand-
book for clinical care. The Primer will educate trainees, update established clini-
cians, and help health care providers from all walks of the profession provide better
care for patients with arthritis and rheumatic diseases.
In achieving these purposes, the Primer continues a tradition of excellence dating
back more than 70 years. The Primer and its precursors have served as a major
learning tool for medical students, house officers, fellows, and allied health profes-
sionals since 1934, when the early publications of the American Committee for the
Control of Rheumatism included the Primer on Rheumatism: Chronic Arthritis in
1934. Since that work, which consisted of a 52-page brochure, the Primer has
evolved into a reference guide of nearly 90 chapters and 4 appendices.
The Primer is designed to provide up-to-date information about the major clini-
cal syndromes seen by primary care physicians, rheumatologists, orthopedic sur-
geons, as well as physician assistants, nurse practitioners, physical and occupational
therapists, and allied health professionals whose expertise contributes to patient
care. Emphasis on the evaluation of the patient, the physical examination including
musculoskeletal signs and symptoms, laboratory and imaging evaluations, and
current and novel therapeutic approaches are essential for all who work in this field.
Arthritis and other rheumatic diseases, which affect more than 46 million Ameri-
cans (including 300,000 children), remain a leading cause of disability and the most
common chronic illness in the United States.
I congratulate the editors on their superb work. In addition, the multiple con-
tributors—many of whom are members of the American College of Rheumatology—
should be thanked for their scholarly contributions to the Primer. Rheumatology
has never been more exciting than it is today, and there is no doubt that the 13th
edition of the Primer reflects this. I join clinicians and patients alike in thanking the
Arthritis Foundation for the continuing achievements of this book.

Michael E. Weinblatt, MD
Professor of Medicine
Harvard Medical School
Brigham and Women’s Hospital
Boston, MA, USA

v
 Preface

Students, residents, and fellows interested in learning about the rheumatic diseases
are faced with the daunting challenge of trying to integrate learning about a multi-
tude of fascinating and diverse clinical disorders with an ever-expanding and
complex body of basic science.
This need encapsulates the principal rationale for the major changes in the 13th
edition of The Primer on the Rheumatic Diseases. Although the first part of all
recent editions of The Primer have summarized succinctly the physiology of tissues
and cells that mediate inflammation and musculoskeletal disease, preparation of the
new edition resulted in the identification of two major problems with this “tried-
and-true” formula. First, for readers who really wished to understand the molecular
basis of rheumatic disease to the depth that would facilitate laboratory research and
improve patient care, the initial chapters no longer provided sufficient detail.
Second, for readers seeking an introduction or update within the clinical realm of
rheumatic disorders, the first part of The Primer bore virtually no relation to the
diseases described so engagingly in the rest of the book. In short, in this era of
increasing integration between the basic and clinical sciences, the preliminary
Primer chapters were at risk for becoming simply the pages thumbed through
quickly to get to the good stuff.
Therefore, in the 13th edition, the clinical descriptions that The Primer has
always done best have been augmented by including the clinically relevant basic
science components in the same sections. Thus, for each major rheumatic disease—
for example, rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and
idiopathic inflammatory myopathies—the chapter describing the clinical and epide-
miological features is accompanied by another chapter devoted to “Pathology and
Pathogenesis.” This second chapter incorporates the appropriate (and updated)
elements from previous Primer chapters entitled “Synovium,” “Articular Carti-
lage,” “The Complement System,” and “Muscle” that are essential to understanding
a particular disease today.
Moreover, this fundamental change in the contents is only the beginning of the
improvements to the 13th edition. Other changes include:

• New chapters on “Clinical Immunology” and “Applied Genetics” designed to

heighten the translational nature of the book.
• Color figures that are particularly important for depicting cutaneous findings and
histopathology.
• An expanded chapter on the cutaneous manifestations of disease, emphasizing
the types of disorders rheumatologists often see in consultation.
• A section devoted entirely to juvenile inflammatory arthritis, with individual
chapters on “Clinical Features,” “Pathology and Pathogenesis,” “Treatment and
Assessment,” and “Special Considerations.”
• Separate chapters on ankylosing spondylitis and the reactive and enteropathic
arthropathies, once lumped together (with psoriatic arthritis) as “seronegative
spondyloarthopathies.”
vii
v ii i P R E F A C E

• A tripling of the text devoted to psoriatic arthritis, an acknowledgement of the

substantial treatment advances in that disorder.
• Individual chapters (and more than doubling of the text) to the metabolic and
inflammatory myopathies, once included in the same chapter.
• Reorganization of the vasculitis section along more rational and all-inclusive
lines, with a chapter entitled “ANCA-Associated Vasculitis” that addresses
together Wegener’s granulomatosis, microscopic polyangiitis, and the Churg-
Strauss syndrome, disorders with striking similarities but important contrasts.
• Now entering its eighth decade, The Primer has rejected strongly the notion that
“If it ain’t broke, don’t fix it.” In view of the recent remarkable strides in under-
standing and treating rheumatic disease, students, trainees, and practicing clini-
cians all need a standard textbook that can change with the times and reflect
these advances. The Primer continues to fill that need. Read, learn, and enjoy.

John H. Klippel, MD
John H. Stone, MD, MPH
Leslie J. Crofford, MD
Patience H. White, MD, MA
 CONTENTS

Foreword by Michael E. Weinblatt . . . . . . . . . . . . . . . . . . . . . . . . . . . v

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii

Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv

1. Public Health and Arthritis: A Growing Imperative . . . . . . . . 1

Patience H. White and Rowland W. Chang

2. Evaluation of the Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

A. History and Physical Examination . . . . . . . . . . . . . . . . . . . 6

David B. Robinson and Hani S. El-Gabalawy

B. Laboratory Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Kerstin Morehead

C. Arthrocentesis, Synovial Fluid Analysis,

and Synovial Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Kenneth H. Fye

D. Imaging of Rheumatologic Diseases . . . . . . . . . . . . . . . . . . 28

William W. Scott, Jr., William J. Didie,
and Laura M. Fayad

3. Musculoskeletal Signs and Symptoms . . . . . . . . . . . . . . . . . . . 42

A. Monarticular Joint Disease . . . . . . . . . . . . . . . . . . . . . . . . . . 42

H. Ralph Schumacher and Lan X. Chen

B. Polyarticular Joint Disease . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Sterling West

C. Neck and Back Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

David Borenstein

D. Regional Rheumatic Pain Syndromes . . . . . . . . . . . . . . . . 68

Joseph J. Biundo, Jr.

E. The Fibromyalgia Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . 87

Dina Dadabhoy and Daniel J. Clauw

4. Molecular and Cellular Basis of Immunity

and Immunological Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Kevin Elias, Richard Siegel, and John J. O’Shea

5. Genetics and Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108

James Kelley and Robert P. Kimberly

6. Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114

A. Clinical and Laboratory Manifestations . . . . . . . . . . . . . 114

Christopher V. Tehlirian and Joan M. Bathon

ix
x CONTENTS

B. Epidemiology, Pathology, and Pathogenesis . . . . . . . . . . 122

Jean-Marc Waldburger and Gary S. Firestein

C. Treatment and Assessment . . . . . . . . . . . . . . . . . . . . . . . . 133

Alyce M. Oliver and E. William St. Clair

7. Juvenile Idiopathic Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142

A. Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142

Daniel J. Lovell

B. Pathology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . 149

Patricia Woo

C. Treatment and Assessment . . . . . . . . . . . . . . . . . . . . . . . . 154

Philip J. Hashkes and Ronald M. Laxer

D. Special Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163

Carol B. Lindsley

8. Psoriatic Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170

A. Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170

Dafna D. Gladman

B. Pathology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . 178

Christopher Ritchlin

C. Treatment and Assessment . . . . . . . . . . . . . . . . . . . . . . . . 185

Philip J. Mease

9. Ankylosing Spondylitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193

A. Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193

Désirée Van der Heijde

B. Pathology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . 200

Juergen Braun

C. Treatment and Assessment . . . . . . . . . . . . . . . . . . . . . . . . 209

John C. Davis, Jr.

10. Reactive and Enteropathic Arthritis . . . . . . . . . . . . . . . . . . . . 217

Robert D. Inman

11. Osteoarthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224

A. Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224

Paul Dieppe

B. Pathology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . 229

Francis Berenbaum

C. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Leena Sharma

12. Gout . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241

A. Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241

N. Lawrence Edwards
 CONTENTS xi

B. Epidemiology, Pathology, and

Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
Hyon K. Choi

C. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
Robert A. Terkeltaub

13. Calcium Pyrophosphate Dihydrate,

Hydroxyapatite, and Miscellaneous Crystals . . . . . . . . . . . . 263
Geraldine McCarthy

14. Infectious Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271

A. Septic Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271

George Ho, Jr.

B. Viral Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277

Leonard H. Calabrese

C. Lyme Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282

Linda K. Bockenstedt

D. Mycobacterial, Fungal, and Parasitic

Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
Steven R. Ytterberg

E. Rheumatic Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297

Stanford Shulman and Preeti Jaggi

15. Systemic Lupus Erythematosus . . . . . . . . . . . . . . . . . . . . . . . 303

A. Clinical and Laboratory Features . . . . . . . . . . . . . . . . . . . 303

Jill P. Buyon

B. Epidemiology, Pathology, and

Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
David S. Pisetsky

C. Treatment and Assessment . . . . . . . . . . . . . . . . . . . . . . . . 327

Susan Manzi and Amy H. Kao

16. Antiphospholipid Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . 339

Michelle Petri

17. Systemic Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343

A. Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343

Maureen D. Mayes

B. Epidemiology, Pathology, and Pathogenesis . . . . . . . . 351

John Varga

C. Treatment and Assessment . . . . . . . . . . . . . . . . . . . . . . . . 359

Maya H. Buch and James R. Seibold

18. Idiopathic Inflammatory Myopathies . . . . . . . . . . . . . . . . . . 363

A. Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363

Robert L. Wortmann
x ii CONTENTS

B. Pathology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . 368

Lisa G. Rider and Frederick W. Miller

C. Treatment and Assessment . . . . . . . . . . . . . . . . . . . . . . . . 375

Chester V. Oddis

19. Metabolic Myopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381

Alan N. Baer

20. Sjögren’s Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389

Troy Daniels

21. Vasculitides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398

A. Giant Cell Arteritis, Polymyalgia Rheumatica,

and Takayasu’s Arteritis . . . . . . . . . . . . . . . . . . . . . . . . . . 398
Cornelia M. Weyand and Jörg J. Goronzy

B. Polyarteritis Nodosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410

Keith T. Rott

C. The Antineutrophil Cytoplasmic

Antibody–Associated Vasculitides: Wegener’s
Granulomatosis, Microscopic Polyangiitis, and
the Churg–Strauss Syndrome . . . . . . . . . . . . . . . . . . . . . . 416
John H. Stone

D. Immune Complex–Mediated Vasculitis . . . . . . . . . . . . . 427

Philip Seo

E. Miscellaneous Vasculitis (Behçet’s Disease, Primary

Angiitis of the Central Nervous System, Cogan’s
Syndrome, and Erythema Elevatum Diutinum) . . . . . . 435
Kenneth T. Calamia and Carlo Salvarani

F. Kawasaki’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444

Barry L. Myones

22. Relapsing Polychondritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451

Harvinder S. Luthra

23. Adult-Onset Still’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455

John M. Esdaile

24. Periodic Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460

John G. Ryan and Daniel L. Kastner

25. Less Common Arthropathies . . . . . . . . . . . . . . . . . . . . . . . . . . 470

A. Hematologic and Malignant Disorders . . . . . . . . . . . . . 470

Adel G. Fam

B. Rheumatic Disease and Endocrinopathies . . . . . . . . . . 479

Peter A. Merkel

C. Hyperlipoproteinemia and Arthritis . . . . . . . . . . . . . . . . 484

Robert F. Spiera
 C O N T E N T S xii i

D. Neuropathic Arthropathy . . . . . . . . . . . . . . . . . . . . . . . . . 488

Ann K. Rosenthal

E. Dermatologic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 492

Jeffrey P. Callen

F. Hypertrophic Osteoarthropathy . . . . . . . . . . . . . . . . . . . . 504

Manuel Martinez-Lavin

26. Complex Regional Pain Syndrome . . . . . . . . . . . . . . . . . . . . . 509

Geoffrey Littlejohn

27. Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514

Edward S. Chen

28. Storage and Deposition Diseases . . . . . . . . . . . . . . . . . . . . . . 523

Duncan A. Gordon

29. The Amyloidoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533

Pasha Sarraf and Jonathan Kay

30. Neoplasms of the Joint . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 543

Andrew J. Cooper, James D. Reeves, and Sean P. Scully

31. Heritable Disorders of Connective Tissue . . . . . . . . . . . . . . . 549

Reed Edwin Pyeritz

32. Bone and Joint Dysplasias . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559

William A. Horton

33. Osteonecrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565

Thorsten M. Seyler, David Marker, and Michael A. Mont

34. Paget’s Disease of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 573

Roy D. Altman

35. Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 576

A. Epidemiology and Clinical Assessment . . . . . . . . . . . . . 576

Kenneth G. Saag

B. Pathology and Pathophysiology . . . . . . . . . . . . . . . . . . . 584

Philip Sambrook

C. Treatment of Postmenopausal Osteoporosis . . . . . . . . 592

Nelson B. Watts

36. Rehabilitation of Patients with Rheumatic

Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 599
Thomas D. Beardmore

37. Psychosocial Factors in Arthritis . . . . . . . . . . . . . . . . . . . . . . . 609

Alex Zautra and Denise Kruszewski

38. Self-Management Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . 614

Teresa J. Brady

39. Pain Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 620

John B. Winfield
x iv C O N T E N T S

40. Therapeutic Injections of Joints and Soft Tissues . . . . . . . 628

Juan J. Canoso

41. Nonsteroidal Anti-Inflammatory Drugs . . . . . . . . . . . . . . . . 634

Leslie J. Crofford

42. Glucocorticoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 644

Frank Buttgereit and Gerd-Rüdiger Burmester

43. Operative Treatment of Arthritis . . . . . . . . . . . . . . . . . . . . . . 651

Joseph A. Buckwalter and W. Timothy Ballard

44. Complementary and Alternative Therapies . . . . . . . . . . . . 664

Erin L. Arnold and William J. Arnold

Appendix I. Criteria for the Classification and Diagnosis

of the Rheumatic Diseases . . . . . . . . . . . . . . . . . . . . 669

Appendix II. Guidelines for the Management of

Rheumatic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . 683

Appendix III. Supplement and Vitamin and

Mineral Guide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 691

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 703
 CONTRIBUTORS

Roy D. Altman, MD Teresa J. Brady, PhD

Professor, Deparment of Medicine/Rheumatology and Senior Behavioral Scientist, Arthritis Program, Centers for
Immunology, University of California, Los Angeles, Los Disease Control and Prevention, Atlanta, GA, USA
Angeles, CA, USA
Juergen Braun, MD
Erin L. Arnold, MD Professor, Department of Rheumatology, Rheumazentrum
Partner/Rheumatologist, Illinois Bone and Joint Institute, Ruhrgebiet, Herne, Germany
The Center for Arthritis and Osteoporosis, Morton Grove,
IL, USA Maya H. Buch, MBchB, MRCP
Clinical Lecturer and Research Fellow, University of Michigan
William J. Arnold, MD Scleroderma Program, University of Michigan Health System,
Partner/Rheumatologist, Illinois Bone and Joint Institute, Ann Arbor, MI, USA; Academic Unit of Musculoskeletal
The Center for Arthritis and Osteoporosis, Morton Grove, Disease, University of Leeds, UK
IL, USA
Joseph A. Buckwalter, MS, MD
Alan N. Baer, MD Professor and Head, Orthopedic Surgery, Department of
Associate Professor, Department of Medicine, Chief, Section Orthopaedics and Rehabilitation, University of Iowa, Iowa
of Rheumatology, University at Buffalo, State University of City, IA, USA
New York, Buffalo, NY, USA
Gerd-Rüdiger Burmester, MD
W. Timothy Ballard, MD Professor, Department of Rheumatology and Clinical
Director, Joint Replacement Center, Department of Immunology, Charité University Hospital, Berlin,
Orthopaedics, Memorial Hospital, Chattanooga, TN, USA Germany
Joan M. Bathon, MD
Frank Buttgereit, MD
Professor, Department of Medicine, Director, Johns Hopkins
Professor, Department of Rheumatology and Clinical
Arthritis Center, Johns Hopkins University School of
Immunology, Charité University Hospital, Berlin,
Medicine, Baltimore, MD, USA
Germany
Thomas D. Beardmore, MD, FACP, FACR
Chief, Department of Rheumatology, Rancho Los Amigos Jill P. Buyon, MD
National Rehabilitation Center, Downey, CA; Professor, Professor, Department of Medicine, Division of Rheumato-
Department of Medicine, Keck School of Medicine, The logy, New York University School of Medicine, New York,
University of Southern California, Los Angeles, CA, USA NY; Director, Lupus Clinic, New York University Hospital
for Joint Diseases, New York, NY, USA
Francis Berenbaum, MD, PhD
Professor, Department of Rheumatology, Saint-Antoine Leonard H. Calabrese, DO
Hospital; University Pierre & Marie Curie, Paris, France Professor, Department of Rheumatic and Immunologic
Diseases, Cleveland Clinic Lerner College of Medicine of
Joseph J. Biundo, Jr., MD Case Western Reserve University, Cleveland Clinic
Clinical Professor, Department of Medicine, Tulane Foundation, Cleveland, OH, USA
University School of Medicine, Kenner, LA, USA
Kenneth T. Calamia, MD
Linda K. Bockenstedt, MD Associate Professor, Department of Medicine, Division
Professor, Department of Internal Medicine, Yale University of Rheumatology, Mayo Clinic College of Medicine,
School of Medicine, New Haven, CT, USA Jacksonville, FL, USA

David Borenstein, MD Jeffrey P. Callen, MD

Clinical Professor of Medicine, The George Washington Professor, Department of Medicine (Dermatology); Chief,
University Medical Center; Arthritis and Rheumatism Division of Dermatology, University of Louisville School of
Associates, Washington, DC, USA Medicine, Louisville, KY, USA

xv
xvi CONTRIBUTORS

Juan J. Canoso, MD, FACP, MACR N. Lawrence Edwards, MD

Attending, American British Cowdray Medical Center, Professor and Vice Chairman, Department of Medicine,
Mexico City, Mexico University of Florida, Gainesville, FL, USA

Rowland W. Chang, MD, MPH Hani S. El-Gabalawy, MD, FRCPC

Professor of Preventive Medicine, Medicine, and Physical Professor, Department of Medicine, Arthritis Centre, Univer-
Medicine and Rehabilitation; Director, Program in Public sity of Manitoba, Winnipeg, Manitoba, Canada
Health, Northwestern University, Feinberg School of
Medicine, Chicago, IL, USA Kevin Elias, MD
Howard Hughes Medical Institute-National Institute of
Edward S. Chen, MD Health Research Scholar, Lymphocyte Cell Biology Section,
Assistant Professor, Department of Medicine, Division of National Institute of Arthritis, Musculoskeletal, and Skin
Pulmonary and Critical Care Medicine, Johns Hopkins Diseases, Bethesda, MD, USA
University School of Medicine, Baltimore, MD, USA
John M. Esdaile, MD, MPH
Lan X. Chen, MD, PhD
Scientific Director, Arthritis Research Centre of Canada;
Clinical Assistant Professor, Department of Medicine/
Professor, University of British Columbia, Vancouver, British
Rheumatology, University of Pennsylvania, Philadelphia, PA,
Columbia, Canada
USA

Hyon K. Choi, MD, MPH, DrPH, FRCPC Adel G. Fam, MD, FRCP(C), FACP
Associate Professor of Medicine and Mary Pack Arthritis Emeritus Professor of Medicine, Department of Medicine,
Society Chair in Rheumatology, Department of Medicine, Division of Rheumatology, Sunnybrook & Women’s College
Division of Rheumatology, The University of British Health Sciences Centre, University of Toronto, Toronto,
Columbia, Vancouver, British Columbia, Canada Ontario, Canada

Daniel J. Clauw, MD Laura M. Fayad, MD

Professor, Department of Internal Medicine, Division of Assistant Professor, The Russell H. Morgan Department
Rheumatology, University of Michigan, Ann Arbor, MI, of Radiology and Radiological Science, Johns Hopkins
USA University School of Medicine, Baltimore, MD, USA

Andrew J. Cooper, MD Gary S. Firestein, MD

Resident, Department of Orthopaedic Surgery, University of Professor, Department of Medicine, Chief, Division of
Miami, Miami, FL, USA Rheumatology, Allergy and Immunology, University of
California San Diego, School of Medicine, La Jolla, CA, USA
Leslie J. Crofford, MD
Gloria W. Singletary Professor of Internal Medicine, Chief, Kenneth H. Fye, MD
Division of Rheumatology & Women’s Health, University of Clinical Professor, Department of Medicine, University of
Kentucky, Lexington, KY, USA California, San Francisco, San Francisco, CA, USA

Dina Dadabhoy, MD
Dafna D. Gladman, MD, FRCPC
Clinical Lecturer, Department of Internal Medicine, Division
Professor, Department of Medicine/Rheumatology, University
of Rheumatology, University of Michigan, Ann Arbor, MI,
of Toronto; Senior Scientist, Toronto Western Research
USA
Institute; Director, Psoriatic Arthritis Program, University
Health Network, Toronto, Canada
Troy Daniels, DDS, MS
Professor, Schools of Dentistry and Medicine, University of
California, San Francisco, San Francisco, CA, USA Duncan A. Gordon, MD, FRCPC, MACR
Professor, Department of Medicine, University of Toronto;
John C. Davis, Jr., MD, MPH Rheumatologist, University Health Network, Toronto
Associate Professor, Department of Medicine, Division of Western Hospital, Toronto, Ontario, Canada
Rheumatology, University of California San Francisco, San
Francisco, CA, USA Jörg J. Goronzy, MD
Co-Director, Department of Medicine, Kathleen B. and
William J. Didie, MD Mason I. Lowance Center for Human Immunology, Emory
Fellow, Musculoskeletal Imaging, Department of Radiology, University School of Medicine, Atlanta, GA, USA
Johns Hopkins University, Baltimore, MD, USA
Philip J. Hashkes, MD, MSc
Paul Dieppe, MD Head, Section of Pediatric Rheumatology, Department of
Professor, Department of Social Medicine, University of Rheumatic Diseases, Cleveland Clinic Foundation, Cleveland,
Bristol, Bristol, UK OH, USA
 C O N T R I B U T O R S x vi i

George Ho, Jr., MD Carol B. Lindsley, MD

Professor, Department of Internal Medicine, Division of Professor, Department of Pediatrics, Director of Pediatric
Rheumatology, Brody School of Medicine at East Carolina Rheumatology, University of Kansas Medical Center, Kansas
University, Greenville, NC, USA City, KS, USA

William A. Horton, MD Geoffrey Littlejohn, MD, MPH, MBBS[Hon], FRACP,

Director, Research Center/Molecular and Medical Genetics, FRCP(Edin)
Shriners Hospital for Children; Professor, Oregon Health and Director of Rheumatology and Associate Professor of
Science University, Portland, OR, USA Medicine, Department of Medicine, Monash University at
Monash Medical Centre, Melbourne, Australia
Robert D. Inman, MD
Professor, Department of Medicine, Division of Rheuma- Daniel J. Lovell, MD, MPH
tology, University of Toronto, Toronto Western Hospital, Joseph Levinson Professor of Pediatrics, Division of
Toronto, Ontario, Canada Rheumatology, Cincinnati Children’s Hospital Medical
Center, Cincinnati, OH, USA
Preeti Jaggi, MD
Assistant Professor, Department of Infectious Diseases, Harvinder S. Luthra, MD
Department of Pediatrics, Ohio State University, Columbus, John Finn Professor of Medicine, Department of
OH, USA Rheumatology, Mayo Clinic College of Medicine, Rochester,
MN, USA
Amy H. Kao, MD, MPH
Assistant Professor, Department of Medicine, Division of Susan Manzi, MD, MPH
Rheumatology and Clinical Immunology, University of Associate Professor, Department of Medicine, Division of
Pittsburgh School of Medicine, Pittsburgh, PA, USA Rheumatology and Clinical Immunology, University of
Pittsburgh School of Medicine, University of Pittsburgh
Daniel L. Kastner, MD, PhD Graduate School of Public Health, Pittsburgh, PA, USA
Chief, Genetics and Genomics Branch; Clinical Director and
Director of Translational Research, National Institute of David Marker, BS
Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Medical Student, Rubin Institute for Advanced Orthopedics,
MD, USA Sinai Hospital of Baltimore, Baltimore, MD, USA

Jonathan Kay, MD Manuel Martinez-Lavin, MD

Associate Clinical Professor, Department of Medicine, Chief, Department of Rheumatology, National Institute of
Harvard Medical School; Director of Clinical Trials, Cardiology, Mexico, DF, Mexico
Rheumatology Unit, Massachusetts General Hospital, Boston,
MA, USA Maureen D. Mayes, MD, MPH
Professor, Department of Internal Medicine, Division of
James Kelley, PhD Rheumatology and Immunogenetics, University of Texas-
Postdoctoral Fellow, Department of Medicine, Division of Houston Medical School, Houston, TX, USA
Clinical Immunology and Rheumatology, University of
Alabama at Birmingham, Birmingham, AL, USA Geraldine McCarthy, MD, FRCPI
Associate Professor/Consultant Rheumatologist, Division of
Robert P. Kimberly, MD Rheumatology, Department of Medicine, University College
Howard L. Holley Professor of Medicine and Director, Divi- Dublin, Dublin/Mater Misericordiae University Hospital,
sion of Clinical Immunology and Rheumatology, Senior Asso- Dublin, Ireland
ciate Dean for Research, Department of Medicine, University
of Alabama at Birmingham, Birmingham, AL, USA Philip J. Mease, MD
Head, Seattle Rheumatology Associates; Chief, Division of
John H. Klippel, MD Rheumatology Research, Swedish Medical Center; Clinical
President and CEO, Arthritis Foundation, Atlanta, GA, Professor, University of Washington School of Medicine,
USA Seattle, WA, USA

Denise Kruszewski, MS Peter A. Merkel, MD, MPH

Graduate Student/Research Assistant, Department of Associate Professor, Department of Medicine, Section of
Psychology, Arizona State University, Tempe, AZ, USA Rheumatology, Boston University School of Medicine,
Boston, MA, USA
Ronald M. Laxer, MD, FRCPC
Vice President, Education and Quality, The Hospital for Frederick W. Miller, MD, PhD
Sick Children; Professor, Department of Pediatrics and Chief, Environmental Autoimmunity Group, Office of
Medicine, The University of Toronto, Toronto, Ontario, Clinical Research, National Institute of Environmental Health
Canada Sciences, National Institutes of Health, Bethesda, MD, USA
x v ii i C O N T R I B U T O R S

Michael A. Mont, MD Ann K. Rosenthal, MD

Director, Rubin Institute for Advanced Orthopedics, Sinai Professor, Department of Medicine, Division of Rheumato-
Hospital of Baltimore, Baltimore, MD, USA logy, Medical College of Wisconsin/Zablocki VA Medical
Center, Milwaukee, WI, USA
Kerstin Morehead, MD
Assistant Clinical Professor, Department of Medicine, Keith T. Rott, MD, PhD
Division of Rheumatology, University of California, San Assistant Professor, Department of Medicine, Division of
Francisco, San Francisco, CA, USA Rheumatology, Emory University School of Medicine,
Atlanta, GA, USA
Barry L. Myones, MD
Associate Professor, Pediatric Rheumatology Center, Baylor John G. Ryan, MB, MRCPI
College of Medicine/Texas Children’s Hospital, Houston, TX, Clinical Fellow, Genetics and Genomics Branch, National
USA Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health, Bethesda, MD, USA
Chester V. Oddis, MD
Professor, Department of Medicine, Division of Rheumato- Kenneth G. Saag, MD, MSc
logy and Clinical Immunology, University of Pittsburgh School Associate Professor, Director, Center for Education and Re-
of Medicine, Pittsburgh, PA, USA search on Therapeutics of Musculoskeletal Disorders, Division
of Clinical Immunology and Rheumatology, University of
Alyce M. Oliver, MD, PhD Alabama at Birmingham, Birmingham, AL, USA
Fellow in Rheumatology, Department of Medicine, Division
of Rheumatology and Immunology, Duke University Medical Carlo Salvarani, MD
Center, Durham, NC, USA Director, Division of Rheumatology, Hospital S. Maria
Nuova, Reggio Emilia, Italy
John J. O’Shea, MD
Scientific Director, National Institute of Arthritis and Muscu- Philip Sambrook, MD, FRACP
loskeletal and Skin Diseases; Chief, Molecular Immunology Professor, Department of Rheumatology, University of
and Inflammation Branch; Chief, Lymphocyte Cell Biology Sydney, Sydney, NSW Australia
Section, National Institutes of Health, Bethesda, MD, USA
Pasha Sarraf, MD, PhD
Michelle Petri, MD, MPH Fellow, Department of Medicine, Division of Rheumatology,
Professor, Department of Medicine, Johns Hopkins University Allergy and Immunology, Massachusetts General Hospital,
School of Medicine, Baltimore, MD, USA Boston, MA, USA

David S. Pisetsky, MD, PhD H. Ralph Schumacher, MD

Chief, Department of Medicine, Division of Rheumatology Professor, Department of Medicine/Rheumatology, Univer-
and Immunology, Duke University School of Medicine, sity of Pennsylvania; VA Medical Center, Philadelphia, PA,
Durham, NC, USA USA

Reed Edwin Pyeritz, MD, PhD William W. Scott, Jr., MD

Professor, Department of Medicine and Genetics, Hospital of Associate Professor, The Russell H. Morgan Department
the University of Pennsylvania, Philadelphia, PA, USA of Radiology and Radiological Science, Johns Hopkins
University School of Medicine, Baltimore, MD, USA
James D. Reeves, MD
Resident, Department of Orthopaedic Surgery, University of Sean P. Scully, MD, PhD
Miami, Miami, FL, USA Professor, Department of Orthopaedics, Miller School of
Medicine, University of Miami, Miami, FL, USA
Lisa G. Rider, MD
Deputy Chief, Environmental Autoimmunity Group, Office James R. Seibold, MD
of Clinical Research, National Institute of Environmental Professor, Department of Internal Medicine/Rheumatology,
Health Sciences, National Institutes of Health, Clinical Director, University of Michigan Scleroderma Program,
Research Center, Bethesda, MD, USA University of Michigan Health System, Ann Arbor, MI, USA

Christopher Ritchlin, MD Philip Seo, MD, MHS

Associate Professor, Department of Medicine, Division of Co-Director, Johns Hopkins Vasculitis Center, Division of
Allergy, Immunology and Rheumatology, University of Rheumatology, Johns Hopkins University School of Medi-
Rochester Medical Center, Rochester, NY, USA cine, Baltimore, MD, USA

David B. Robinson, MD, MSc, FRCPC Thorsten M. Seyler, MD

Associate Professor, Department of Medicine, Arthritis Center for Joint Preservation and Reconstruction, Rubin
Centre, University of Manitoba, Winnipeg, Manitoba, Institute for Advanced Orthopedics, Sinai Hospital of
Canada Baltimore, Baltimore, MD, USA
 C O N T R I B U TO R S xi x

Leena Sharma, MD Jean-Marc Waldburger, MD, PhD

Professor, Department of Internal Medicine, Division of Post-Doctoral Scholar, Department of Medicine, Division
Rheumatology, Feinberg School of Medicine at Northwestern of Rheumatology, Allergy, and Immunology, University of
University, Chicago, IL, USA California San Diego School of Medicine, La Jolla, CA,
USA
Stanford Shulman, MD
Chief, Department of Infectious Diseases; Professor, Nelson B. Watts, MD
Department of Pediatrics, Northwestern University Feinberg Professor, Department of Internal Medicine, University of
School of Medicine/The Children’s Memorial Hospital, Cincinnati College of Medicine, Cincinnati, OH, USA
Chicago, IL, USA
Sterling West, MD
Richard Siegel, MD, PhD Professor, Department of Rheumatology, University of
Principal Investigator, Immunoregulation Group, National Colorado Health Sciences Center, Denver, CO, USA
Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health, Bethesda, MD, USA Cornelia M. Weyand, MD
Co-Director, Kathleen B. and Mason I. Lowance Center for
Robert F. Spiera, MD Human Immunology, Department of Medicine, Emory
Adjunct Clinical Instructor, Department of Medicine/ University School of Medicine, Atlanta, GA, USA
Rheumatology, Mount Sinai School of Medicine, New York,
NY, USA Patience H. White, MD, MA
Chief Public Health Officer, Arthritis Foundation, Atlanta,
E. William St. Clair, MD GA, USA
Professor, Department of Medicine, Division of Rheuma-
tology and Immunology, Duke University Medical Center, John B. Winfield, MD
Durham, NC, USA Smith Distinguished Professor of Medicine Emeritus,
Department of Medicine, University of North Carolina,
John H. Stone, MD, MPH Chapel Hill, NC, USA
Associate Physician, Massachusetts General Hospital; Deputy
Editor for Rheumatology, UpToDate, Boston, MA, USA Patricia Woo, BSc, MBBS, PhD, MRCP, FRCP, CBE
Professor, Department of Immunology and Molecular
Christopher V. Tehlirian, MD Pathology, University College London, London, UK
Post-Doctoral Fellow, Department of Medicine, Division of
Clinical and Molecular Rheumatology, Johns Hopkins Robert L. Wortmann, MD, FACP, FACR
University School of Medicine, Baltimore, MD, USA Professor and C. S. Lewis, Jr., MD Chair of Medicine,
Department of Internal Medicine, The University of
Robert A. Terkeltaub, MD Oklahoma College of Medicine, Tulsa, OK, USA
Chief, Rheumatology Section, Department of Medicine,
Veterans Affairs Medical Center San Diego; Professor, Steven R. Ytterberg, MD
Department of Medicine, University of California San Diego Associate Professor, Department of Medicine, Division of
School of Medicine, San Diego, CA, USA Rheumatology, Mayo Clinic College of Medicine, Rochester,
MN, USA
Désirée Van der Heijde, MD, PhD
Professor, Department of Rheumatology, University Hospital Alex Zautra, PhD
Maastricht, The Netherlands Foundation Professor, Department of Psychology, Arizona
State University, Tempe, AZ, USA
John Varga, MD
Gallagher Professor of Medicine, Department of Medicine,
Division of Rheumatology, Northwestern University Feinberg
School of Medicine, Chicago, IL, USA