oxford american handbook of rheumatology

Oxford American Handbook of
Rheumatology
Second Edition
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1
Oxford American
Handbook of
Rheumatology
Second Edition
Philip Seo
Director, The Johns Hopkins Vasculitis Center
Director, Johns Hopkins Rheumatology Fellowship
Associate Professor of Medicine
Division of Rheumatology
The Johns Hopkins University School of Medicine
with
Alan J. Hakim
Gavin P.R. Clunie
Inam Haq

3
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Library of Congress Cataloging-in-Publication Data
Seo, Philip.
Oxford American handbook of rheumatology / Philip Seo.—2nd ed.
p. ; cm.—(Oxford American handbooks)
Handbook of rheumatology
Adapted from: Oxford handbook of rheumatology / Alan J. Hakim,
Gavin P.R. Clunie, Inam Haq. 3rd ed. 2011.
Includes bibliographical references and index.
ISBN 978–0–19–990799–1 (alk. paper)
I. Hakim, Alan. Oxford handbook of rheumatology. II. Title. III. Title:
Handbook of rheumatology. IV. Series: Oxford American handbooks.
[DNLM: 1. Rheumatic Diseases—Handbooks. WE 39]
LCClassifi cation not assigned
616.7′23—dc23 2012035653

9 8 7 6 5 4 3 2 1
Printed in the United States of America
on acid-free paper
This material is not intended to be, and should not be considered, a sub-
stitute for medical or other professional advice. Treatment for the con-
ditions described in this material is highly dependent on the individual
circumstances. Although this material is designed to offer accurate infor-
mation with respect to the subject matter covered and to be current as
of the time it was written, research and knowledge about medical and
health issues are constantly evolving and dose schedules for medica-
tions are being revised continually, with new side effects recognized and
accounted for regularly. Readers must therefore always check the product
information and clinical procedures with the most up-to-date published
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disclaim, any responsibility for any liability, loss, or risk that may be claimed
or incurred as a consequence of the use and/or application of any of the
contents of this material.
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vii
Foreword
Patients with rheumatic disorders present so many different challenges
that almost every practicing physician needs some familiarity with rheu-
matology. An abbreviated litany of common rheumatic symptoms and
signs–arthralgias, myalgias, weakness, back pain, and neck pain–reinforces

the observation that rheumatic disorders are among the most frequent
reasons patients present to family physicians, general internists, geriatri-
cians, and orthopedists. Although many rheumatic diseases are temporary
nuisances, others can cause life-threatening, multisystem diseases that can
be encountered by hospitalists, critical care specialists, nephrologists, car-
diologists, neurologists, and a myriad of other consultants. Distinguishing
among the more than 150 different forms of arthritis, although often chal-
lenging, is important, given the recent dramatic increase in specifi c and
effective therapies that are now available.
Fortunately, this handbook will offer any physician substantial help in
meeting the challenges posed by rheumatic diseases. The liberal use of
bulleted summary points and tables makes this handbook both concise
and thorough. Physicians eager to improve their clinical skills will enjoy
the excellent photographs that illustrate important aspects of the muscu-
loskeletal physical examination. The chapter on rheumatic emergencies
will be especially useful to hospitalists.
I believe this handbook will allow many physicians to experience the joy
and sense of accomplishment that can come from diagnosing and treating
patients with rheumatic diseases.
David B. Hellmann, M.D., M.A.C.P.
Aliki Perroti Professor of Medicine
Vice Dean, Johns Hopkins Bayview Medical Center
Chairman, Department of Medicine Johns Hopkins Bayview
The Johns Hopkins University School of Medicine
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ix
Preface
Rheumatology is one of the last great frontiers in medicine. In this modern
era, in which we hear less about neck veins and more about BNP levels,
rheumatology remains the exception to the rule. Despite the growing

number of diagnostic tests we have at our disposal, they remain a mere
adjunct to the patient evaluation. This is one of the last subspecialties in
which it is not only common, but appropriate, to ignore a positive ANA or
joint space narrowing, and instead listen to what the patient has to say.
That said, rheumatology is a fi eld in transition. Long behind us are the days
in which clinical trials compared the effi cacy of one NSAID to another.
The advent of biologic agents in particular has led to a new era in thera-
peutics in which largely nonspecifi c immunosuppressive drugs are being
replaced by progressively more nuanced agents. The day that molecular
phenotyping of patients joins clinical phenotyping as a way of selecting
treatment strategies cannot be far behind.
During the last few years, the rate of transitions has occurred at break-
neck speed. Since the publication of the fi rst edition, new classifi cation
criteria have been published for systemic lupus erythematosus, Sj ö gren’s
syndrome, polymyalgia rheumatica, and rheumatoid arthritis. For the fi rst
time, we have FDA-approved agents for the treatment of both systemic
lupus erythematosus and ANCA-associated vasculitis. Finally, we are start-
ing to see oral biologic agents hit the market, allowing patients to take
advantage of our most advanced therapeutics without subjecting them
to the needle.
For the present, rheumatology encompasses a dizzying amount of infor-
mation; no book can be expected to replace years of clinical experience.
I believe and hope, however, that this book will fi nd a home in many
white-coat pockets, from the attending who just needs to refresh his or
her memory on a few details, to the trainee who is looking for some way
of getting a toehold in this daunting fi eld.
More than anything else, this book is meant to provide you with an
approach to the patient, and a framework on which you can build. This
book represents just the beginning of a continually evolving, continuously
changing story that never fails to fascinate.

Philip Seo, MD, MHS
Director, the Johns Hopkins Vasculitis Center
Director, Johns Hopkins Rheumatology Fellowship
Associate Professor of Medicine
Johns Hopkins University School of Medicine
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xi
Acknowledgments
Last year, I became Director of the Rheumatology Fellowship at Johns
Hopkins, and with that new position came a deep sense of obligation to
improve my general understanding of rheumatology—no small feat after
many years of seeing only patients with systemic vasculitis.
My new position has allowed me to work even more closely with my col-
leagues, and has left me awestruck by the depths of both their knowledge
and their generosity.
As I have said before, the greatest gift that a fellow academic can give is
his or her time. I am therefore pleased to thank publicly my friends and
colleagues who graciously reviewed these chapters during airport layo-
vers and other moments stolen from far more deserving obligations: Alan
Baer, Clifton (Bing) Bingham, Lisa-Christopher-Stine, Fred Wigley, Grant
Louie, Laura Hummers, Khalil Ghanem, Michelle Petri, Geeta Sood, and
Sangeeta Sule.
This motley crew gently (or not so) informed me when I was woefully
misinformed—which was more often than I would like to admit—and
credit for many of the improvements to this second edition really belongs
to them.
I also wish to thank Antony Rosen and David Hellmann, whose avuncular
support has provided my career with a second act.
I continue to be grateful to Alan Hakim, Gavin Clunie, and Inam Haq, who
wrote the original Oxford Handbook of Rheumatology, and provided the

backbone (and much of the meat) for this current edition. Also, I would
be remiss if I did not thank Andrea Seils, Senior Editor of Clinical Medicine
at Oxford University Press, whose encouragement and support have been
invaluable.
Finally, I dedicate this work to my family, who mean more to me with each
passing year: Kyung Hwa Seo, Hae Ja Yoon Seo, Susan Seo, and Ellen Seo. I
also dedicate this work to my niece and nephew, Avery Pusey and Jackson
Pusey, who—as they pointed out to me—I had neglected to name in the
fi rst edition, but are never far from my heart.
Philip Seo
Baltimore
February 2013
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xiii
Contents
Detailed contents xv
List of color plates xxi
Symbols and abbreviations xxiii
Part 1: The presentation of rheumatic disease
1 Evaluating musculoskeletal pain 3
2 Regional musculoskeletal conditions: making a
working diagnosis 11
3 Patterns of disease presentation: making
a working diagnosis 149
4 The spectrum of presentation of rheumatic
disease 195
Part 2: The clinical features and management
of rheumatic diseases
5 Rheumatoid arthritis (RA) 235
6 Osteoarthritis (OA) 261

7 The crystal arthropathies 271
8 The spondyloarthropathies 283
9 Juvenile idiopathic arthiritis (JIA) 309
10 Systemic lupus erythematosus (SLE) 329
11 The antiphospholipid (antibody)
syndrome (APS) 351
12 Sj ö gren’s syndrome (SS) 361

13 Systemic sclerosis and related disorders 373
14 Idiopathic infl ammatory myopathies—
polymyositis (PM) and dermatomyositis (DM) 397
15 Primary vasculitides 417
xiv
CONTENTS CONTENTS
16 Metabolic bone diseases and disorders
of collagen 443
17 Infection and rheumatic disease 481
18 Miscellaneous conditions 499
19 Common upper limb musculoskeletal lesions 529
20 Back pain 537
21 Complementary and alternative medicine
in rheumatology 553
22 Rheumatologic emergencies 561
Index 577
xv
Detailed contents
List of color plates xxi
Symbols and abbreviations xxiii
Part 1 The presentation of rheumatic disease
1 Evaluating musculoskeletal pain 3

Introduction 4
Localization of pain and pain patterns 6
Changes in pain on examination 8
The assessment of pain in young children 9
2 Regional musculoskeletal conditions: making
a working diagnosis 11
Introduction 12
Neck pain 14
Shoulder pain 22
Pain around the elbow 34
Wrist pain 40
Symptoms in the hand 46
Upper limb peripheral nerve lesions 58
Thoracic back and chest pain 64
Low back pain and disorders in adults 70
Spinal disorders in children and adolescents 84
Pelvic, groin, and thigh pain 92
Knee pain 104
Lower leg and foot disorders (adults) 118
Child and adolescent foot disorders 132
Corticosteroid injection therapy 142
Principles of rehabilitation 146
3 Patterns of disease presentation: making a working
diagnosis 149
Monoarticular pains in adults 150
Oligoarticular pains in adults 152
xvi
DETAILED CONTENTS
Oligoarticular pains in children and adolescents 162
Widespread pain in adults 170

Widespread pain in children and adolescents 186
4 The spectrum of presentation of rheumatic disease 195
Skin disorders and rheumatic disease 196
Skin vasculitis in adults 202
Skin vasculitis in children and adolescents 206
Cardiac manifestations 210
Pulmonary manifestations 214
Renal manifestations 216
Endocrine manifestations 220
Gut and hepatobiliary manifestations 224
Malignancy 230
Part 2 The clinical features and management
of rheumatic diseases
5 Rheumatoid arthritis (RA) 235
Disease criteria and epidemiology 236
Incidence, prevalence, and morbidity 238
The clinical features of rheumatoid arthritis 239
Organ disease in rheumatoid arthritis 240
The evaluation and treatment of rheumatoid arthritis 244
Rheumatoid factor positive polyarthritis in childhood 259
6 Osteoarthritis (OA) 261
Introduction 262
Clinical features of OA 264
The investigation of OA 266
The management of OA 268
7 The crystal arthropathies 271
Gout and hyperuricemia 272
Calcium pyrophosphate dihydrate (CPPD) disease 278
Basic calcium phosphate (BCP) associated disease 281
Calcium oxalate arthritis 282

xvii
DETAILED CONTENTS
8 The spondyloarthridities 283
Introduction 284
Diagnostic criteria and clinical subsets 286
Ankylosing spondylitis 290
Psoriatic arthritis 296
Reactive arthropathy 300
Enteric arthropathy 302
Undifferentiated spondyloarthritis 303
SAPHO 304
Spondyloarthridities in childhood 306
9 Juvenile idiopathic arthritis (JIA) 309
Introduction 330
Oligoarthritis 312
Systemic arthritis 316
Rheumatoid factor negative polyarthritis in childhood 321
Rheumatoid factor negative polyarticular JIA 322
Rheumatoid factor positive polyarticular JIA 324
Juvenile psoriatic arthritis 325
Enthesitis related arthritis 326
Chronic, infantile, neurological, cutaneous, & articular
syndrome (CINCA) 327
Still’s disease 328
10 Systemic lupus erythematosus (SLE) 329
Introduction 330
The clinical features of SLE 334
Antiphospholipid (antibody) syndrome and SLE 338
Pregnancy and SLE 339
Diagnosis and investigation of SLE 340

Drug-induced lupus erythematosus (DILE) 342
The treatment of SLE 344
Prognosis and survival in SLE 348
Childhood SLE 349
Neonatal SLE 350
xviii
DETAILED CONTENTS
11 The antiphospholipid (antibody) syndrome (APS) 351
Introduction 352
Epidemiology and pathology 353
Clinical features of APS 354
Treatment of APS 356
Catastrophic APS (CAPS) 358
12 Sj ö gren’s syndrome (SS) 361
Epidemiology and pathology 362
Clinical manifestations of SS 364
Investigation of SS 368
Treatment of SS 370
13 Systemic sclerosis and related disorders 373
Epidemiology and diagnostic criteria 374
Cutaneous features of scleroderma and
their treatment 380
Systemic features of the disease, investigation,
and treatment 384
Antifi brotic and immunosuppressive therapies for systemic
sclerosis 390
Summary—the approach to systemic sclerosis 392
Scleroderma-like fi brosing disorders
394
14 Idiopathic infl ammatory myopathies—

polymyositis (PM) and dermatomyositis (DM) 397
Epidemiology and diagnosis 398
Clinical features of PM and DM 400
Investigation of PM and DM 404
Autoantibodies in myositis 406
Treatment of PM and DM 410
Inclusion-body myositis (IBM) 413
PM and DM in children 414
15 Primary vasculitides 417
Introduction 418
Large-vessel vasculitis 421
DETAILED CONTENTS
xix
Takayasu’s arteritis 422
Polymyalgia rheumatica and giant cell arteritis 424
Polyarteritis nodosa 429
Granulomatosis with polyangiitis (Wegener’s granulomatosis) 430
Other forms of AAV: microscopic polyangiitis (MPA) and
eosinophilic granulomatosis with polyangiitis (EGPA) 434
Small-vessel and single organ vasculitis 438
Kawasaki disease 442
16 Metabolic bone diseases and disorders of
collagen 443
Osteoporosis 444
Osteomalacia and rickets 454
Parathyroid disease and related disorders 458
Paget’s disease of bone 466
Miscellaneous diseases of bone 470
Molecular abnormalities of collagen and fi brillin 474
17 Infection and rheumatic disease 481

Introduction 482
Pyogenic nongonococcal and gonococcal arthritides 486
Mycobacterium tuberculosis 490
Osteomyelitis 492
Lyme disease 494
Rheumatic fever 496
18 Miscellaneous conditions 499
Beh ç et’s disease 500
Sarcoidosis 504
Miscellaneous skin conditions associated with arthritis 508
Chronic regional pain syndrome 514
Relapsing polychondritis 516
Miscellaneous disorders of synovium 518
Amyloidosis 520
Fibromyalgia and chronic widespread pain 524
xx
DETAILED CONTENTS
19 Common upper limb musculoskeletal lesions 529
Shoulder (subacromial) impingement syndrome 530
Adhesive capsulitis (AC) 533
Lateral epicondylitis (tennis elbow) 534
20 Back pain 537
Conditions causing acute or subacute back
pain in adults 538
Management of chronic back pain 544
Management of back pain in children and adolescents 546
21 Complementary and alternative medicine in
rheumatology 553
Introduction 554
Herbal remedies (phytotherapy) 555

Physical and hands-on therapies 556
Homeopathy 557
Other CAMs 558
22 Rheumatologic emergencies 561
Septic arthritis 562
Infections in patients taking anti-TNF -A drugs 566
Acute SLE 568

Systemic vasculitis 574
Scleroderma (Scl) crises 575
Methotrexate-induced pneumonitis 576
Index 577
xxi
List of color plates
Plate 1 MR scan of the neck showing loss of height and signal affecting
several discs with multisegmental spondylotic bars, compression of the
cord from protrusion of the C5/6 disc and myelopathic changes (high sig-
nal) in the cord.
Plate 2 Patterns of radiographic abnormality in chronic SAI: sclerosis and
cystic changes in greater tuberosity.
Plate 3 Dactylitis, nail changes, and DIP joint arthritis in psoriatic arthritis.
Plate 4 (a) Normal nailfold capillaries. (b) Nailfold capillaries in sclero-
derma showing avascular areas and dilated capillaries in an irregular orien-
tation (original magnifi cation 65x).
Plate 5 Diffuse arm and hand swelling in chronic regional pain syndrome
(refl ex sympathetic dystrophy).
Plate 6 Slight fl exion of fourth and fi fth fi ngers as a result of an ulnar
nerve lesion at the elbow. The area of sensory loss is indicated by the
dotted line.
Plate 7 Psoriatic spondylitis: Nonmarginal and “fl oating” (nonattached)

syndesmophytes.
Plate 8 Spondylolysis. The defect in the pars interarticularis (black arrows)
may only be noted on an oblique view. The patient has had a spinal fusion
(open arrows).
Plate 9 Testing passive hip fl exion and rotational movements (a) and
hip abduction (b).The pelvis should be fi xed when testing abduction and
adduction.
Plate 10 Bone scintigraphy showing osteonecrosis of the left femoral head
(on the right-hand side as this is an anterior view). Photopenia (an early
sign) corresponds to ischemia.
Plate 11 The “patellar tap” test. Any fl uid in the suprapatellar pouch is
squeezed distally by the left hand. The patella is depressed by the right
hand. It will normally tap the underlying femur immediately. Any delay in
eliciting the tap or a feeling of damping as the patella is depressed suggests
a joint effusion.
Plate 12 Injection of the glenohumeral joint via the anterior route.
Plate 13 Injection of the subacromial space.
Plate 14 Injection of tennis elbow (lateral humeral epicondylitis/enthesitis).
xxii
LIST OF COLOR PLATES
Plate 15 Injection of the carpal tunnel to the ulnar side of the palmaris
longus tendon.
Plate 16 Nodules associated with joint diseases. (a) RA: typically over
extensor surfaces and pressure areas. (b) Chronic tophaceous gout: tophi
can be indistinguishable clinically from RA nodules though may appear as
eccentric swellings around joints (image provided courtesy of Dr. R. A.
Watts). (c) Multicentric reticulohistiocytosis: nodules are in the skin, are
small, yellowish-brown, and are often around nails. (d) Nodal OA: swelling
is bony, typically at PIPs and DIPs.
Plate 17 Bone scintigraphy (

99m
Tc MDP) of a 65-year-old man with wide-
spread bone pain and weakness suspected to have metastatic malignancy.
Undecalcifi ed transiliac bone biopsy confi rmed severe osteomalacia.
There was coincidental Paget’s disease (arrowed lesions).
Plate 18 Increased growth of the left lower limb due to chronic knee
infl ammation in (RF-) JIA.
Plate 19 Lupus pernio presenting as a bluish-red or violaceous swelling of
the nose extending onto the cheek.
Plate 20 Nailfold capillaries, demonstrating normal capillary loops.
Magnifi ed 300x. Photograph used with the kind permission of Graham
Dinsdale, Tonia Moore, and Ariane Herrick.
Plate 21 Nailfold capillaries, demonstrating abnormal capillary loops,
including capillary loop dilatation and dropout. Magnifi ed 300x. Photograph
used with the kind permission of Graham Dinsdale, Tonia Moore, and
Ariane Herrick.
xxiii
Symbols and abbreviations
1 alert/warning
p Primary
s Secondary
i increase/raise
d decrease/reduce
4 male(s)
5 female(s)
9 plus or minus
A Alpha
B Beta
ACA Anticentromere antibody
AC(J) Acromioclavicular (joint)

ACR American College of Rheumatology
ADM Abductor digiti minimi
ALP Alkaline phosphatase
ALT Alanine transaminases
ANA Anti-nuclear antibody
ANCA Antineutrophil cytoplasmic antibody
AP Anteroposterior
APB Abductor pollicis brevis
APL Abductor pollicis longus
APS Antiphospholipid (antibody) syndrome
ARA American Rheumatism Association
AS Ankylosing spondylitis
AST Aspartate transaminase
ASOT Antistreptolysin O titer
ASU Avocado/soybean unsaponifi able
AZA Azathioprine
BCP Basic calcium phosphate (crystals)
bid Twice daily
BJHS Benign joint hypermobility syndrome
xxiv
SYMBOLS AND ABBREVIATIONS
BMC Bone mineral content
BMD Bone mineral density
BSR British Society of Rheumatology
C Cervical (e.g., C6 is the sixth cervical vertebra)
CA Coracoacromial
CBC Complete blood count
CINCA Chronic, infantile, neurological, cutaneous, and
articular syndrome
CK Creatine phosphokinase

CMC(J) Carpometacarpal (joint)
CMP Comprehensive metabolic panel
CMV Cytomegalovirus
CPPD Calcium pyrophosphate deposition (arthritis)
CREST Calcinosis, Raynaud’s, Esophageal dysmotility,
Sclerodactyly, Telangiectasia (syndrome)
CRP C-reactive protein
CS Congenital scoliosis
CSS Churg–Strauss syndrome
CT Computed tomography
CTS Carpal tunnel syndrome
CXR Chest radiograph
dcSScl Diffuse cutaneous systemic sclerosis
DEXA/
DXA
Dual-energy X-ray absorptiometry
DIP(J) Distal interphalangeal (joint)
DISH Diffuse idiopathic skeletal hyperostosis
DLCO Diffusion capacity for carbon monoxide
DM Dermatomyositis
DMARD Disease-modifying antirheumatic drug
DVT Deep vein thrombosis
EA Enteropathic arthritis
EBV Epstein–Barr virus
ECG (EKG) Electrocardiogram
ECM Erythema chronicum migrans