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Oxford Handbook of
Rheumatology
Fourth Edition

Gavin Clunie
Consultant Rheumatologist and Metabolic Bone Physician,
Addenbrooke’s Hospital, Cambridge, UK

Nick Wilkinson
Consultant Paediatric and Adolescent Rheumatologist,
Evelina London Children’s Hospital, London, UK

Elena Nikiphorou
Consultant Rheumatologist, Whittington Hospital;
Clinical Researcher, Academic Rheumatology Department,
King’s College London, UK

Deepak Jadon
Consultant Rheumatologist and Director of the
Rheumatology Research Unit,
Addenbrooke’s Hospital, Cambridge, UK

1
1
Great Clarendon Street, Oxford, OX2 6DP,
United Kingdom
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and education by publishing worldwide. Oxford is a registered trade mark of
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© Oxford University Press 2018
The moral rights of the authors have been asserted
First Edition published in 2002
Second Edition published in 2006
Third Edition published in 2011
Fourth Edition published in 2018
Impression: 1
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 v

Foreword

I am pleased to introduce you to the 4th edition of the Oxford Handbook

of Rheumatology. This edition has increased in size, but continues to be just
as accessible. It presents the reader with a pragmatic approach to making
a differential diagnosis. The approach to thinking about how to make sense
of the history and clinical findings is clear. The common rheumatological
conditions are covered well, and the new edition incorporates relevant sec-
tions on paediatric and adolescent rheumatology.
From the days of Sir William Osler, the art of listening to and observing
the patient has been a key focus of what defines a good doctor. Medicine
has advanced considerably since his day, but the core values of a physician
have not changed.
The focus on good clinical history taking and examination technique is a
reminder of the core skill set that we use as physicians. When all else fails,
go back to the basic principles, and back to the patient. This book shows us
how important that skill set is.
Professor Jane Dacre MD, PRCP
President
Royal College of Physicians
London, UK
vi

Preface

Rheumatic musculoskeletal conditions are common both in general and

hospital practice. Musculoskeletal symptoms are a primary feature of many
multisystem illnesses, not only in the autoimmune joint and connective tis-
sue diseases, but also metabolic, endocrine, neoplastic, and infectious con-
ditions. Symptoms are also common in the context of injury, age-​related
change, and psychological distress. Many conditions in rheumatology are a
major source of morbidity and mortality.
We have kept the format of the previous edition for this version but
importantly have updated the text to include paediatric and adolescent
rheumatology.
Part I remains as a guide to evaluation of rheumatic and musculoskeletal
disease from the point of referral and reflects the way clinical problems/​
symptoms present to the clinician in real life. We have considered how this
happens for adults, and new in this version, for children and adolescents,
affected by rheumatological and musculoskeletal disease. The reader will
find detail on musculoskeletal anatomy and functional anatomy in this part
of the book.
Part II remains as the section of the book where the reader can find
disease-​specific information (e.g. spondyloarthritis, vasculitis, back pain, and
so on). We have included paediatric sections in each chapter where there
is relevance for disease occurring in children and adolescents, noting the
difference in disease and its management in children and adolescents com-
pared with adults.
Part III remains as medicine management and contains chapters on drugs
used in rheumatology practice, glucocorticoid injection therapy, and rheu-
matological emergencies.
We have tried to avoid duplication but cross reference between chap-
ters. We hope this book is helpful and informative for all doctors, physio-
therapists, and specialist nursing practitioners who are faced with managing
people and patients with undiagnosed musculoskeletal symptoms or estab-
lished rheumatic musculoskeletal diseases.
 vii

Acknowledgements

The authors would like to acknowledge the work of the co-​founder author-​
editor of the textbook Dr Alan Hakim for his contribution, whom together
with Dr Clunie, devised and wrote the book from the first edition and co-​
author-​editor Dr Inam Haq (who joined for the 2nd and 3rd editions), in
helping to establish the Oxford Handbook of Rheumatology as the market
leader small textbook for rheumatology.
 ix

Contents

Contributors xi
Symbols and abbreviations xii

Part I The presentation of rheumatic disease

1 Evaluating rheumatological and
musculoskeletal symptoms    3
2 Musculoskeletal assessment and patterns
of disease: making a working diagnosis   25
3 Regional musculoskeletal symptoms:
making a working diagnosis   71
4 The spectrum of disorders associated with adult
rheumatic and musculoskeletal diseases 205

Part II T
 he clinical features and management
of rheumatic diseases
5 Rheumatoid arthritis 243
6 Osteoarthritis 265
7 Crystal-​induced musculoskeletal disease 277
8 The spondyloarthritides including
psoriatic arthritis 293
9 Juvenile idiopathic arthritis 321
10 Systemic lupus erythematosus 343
11 Antiphospholipid syndrome 375
12 Sjögren’s syndrome 389
13 Systemic sclerosis and related disorders 401
14 Idiopathic inflammatory myopathies including
polymyositis and dermatomyositis 425
x CONTENTS

15 Primary vasculitides 447

16 Metabolic bone diseases 483
17 Infection and rheumatic disease 525
18 Rare autoinflammatory and miscellaneous diseases 541
19 Hereditary disorders of connective tissue 577
20 Common upper limb musculoskeletal lesions 595
21 Spinal disorders and back pain 605
22 Chronic pain syndromes 623

Part III Medicine management and emergencies

23 Drugs used in rheumatology practice 645
24 Glucocorticoid injection therapy 689
25 Rheumatological emergencies 707

Index 729
 xi

Contributors

Dr Emma Davies Dr Ritu Malayia

Specialist Registrar in Specialist Registrar in
Rheumatology, Royal National Rheumatology, Guys and
Hospital for Rheumatic Diseases, St Thomas’ Hospital NHS
Bath, UK Foundation Trust, London, UK
Dr Catherine Fairris Dr Seraina Palmer
Specialist Registrar in Fellow in Paediatric
Rheumatology, Royal National Rheumatology, Kinderspital,
Hospital for Rheumatic Diseases, Zürich, Switzerland
Bath, UK
Dr Elizabeth Reilly
Dr Shabina Habibi Specialist Registrar in
Senior Clinical Research Fellow, Rheumatology, Royal National
Royal National Hospital for Hospital for Rheumatic Diseases,
Rheumatic Diseases, Bath, UK Bath, UK
Dr Philip Hamann Dr Maliha Sheikh
PhD Research Fellow & Specialist Registrar in
Specialist Registrar in Rheumatology, Addenbrooke’s
Rheumatology, Royal National Hospital, Cambridge University
Hospital for Rheumatic Diseases, Hospitals NHS Foundation Trust,
Bath, UK Cambridge, UK
Dr Dobrina Hull Dr Giulia Varnier
Specialist Registrar in Fellow in Paediatric
Rheumatology, Guys and Rheumatology, Evelina London
St Thomas’ Hospital NHS Children’s Hospital, Guys and
Foundation Trust, London, UK St Thomas’ Hospital NHS
Foundation Trust, London, UK
Dr Eiphyu Htut
Specialist Registrar in Dr Natasha Weisz
Rheumatology, Addenbrooke’s Specialist Registrar in
Hospital, Cambridge University Rheumatology, The Whittington
Hospitals NHS Foundation Trust, Hospital NHS Trust, London, UK
Cambridge, UK
Dr Cee Yi Yong
Dr Anthony Isaacs Specialist Registrar in
Specialist Registrar in Rheumatology, Norfolk and
Rheumatology, The Whittington Norwich University Hospitals
Hospital NHS Trust, NHS Foundation Trust,
London, UK Norwich, UK
xii

Symbols and abbreviations

E cross-​reference
α alpha
β beta
i increased
d decreased
n normal
> greater than
< less than
7 approximately
∴ therefore
AAV ANCA-​associated vasculitis
ABA abatacept
AC adhesive capsulitis
ACA anticentromere antibody
ACE angiotensin-​converting enzyme
AChA acrodermatitis chronicum atrophicans
AC( J) acromioclavicular (joint)
ACL anticardiolipin
ACPA anticitrullinated peptide antibody(-​ies)
ACR American College of Rheumatology
AD autosomal dominant
ADM abductor digiti minimi
AFF atypical femoral fracture
AICTD autoimmune connective tissue disease
AIS autoinflammatory syndrome
AKI acute kidney injury
ALNT anterolateral neospinothalamic tract
ALP alkaline phosphatase
ALT alanine transaminase
AMA amyloid A
AML amyloid L
ANA antinuclear antibody
ANCA antineutrophil cytoplasmic antibody
Anti-​β2GP1 β2 glycoprotein-​1
anti-​
AOSD adult-​onset Still’s disease
AP anteroposterior
 SYMBOLS AND ABBREVIATIONS xiii

APB abductor pollicis brevis

APL abductor pollicis longus
APL antiphospholipid
APRIL a proliferation inducing-​ligand
APS antiphospholipid (antibody) syndrome
APTT activated partial thromboplastin time
AR autosomal recessive
ARA American Rheumatism Association
ARB angiotensin II receptor blocker
ARDS adult respiratory distress syndrome
ARTEMIS Abatacept Treatment in Polymyositis and
Dermatomyositis trial
AS ankylosing spondylitis
ASAS Assessment of Spondyloarthritis International Society
AST aspartate transaminase
ASOT antistreptolysin O titre
ASU avocado/​soybean unsaponifiable
ATN acute tubular necrosis
axSpA axial spondyloarthritis
AZA azathioprine
β2GP1 β2 glycoprotein-​1
BAFF B-​cell activating factor (see also BLyS)
BAL bronchoalveolar lavage
BCP basic calcium phosphate (crystals)
BD Behçet’s disease
bDMARD biologic disease-​modifying antirheumatic drug
BILAG British Isles Lupus Assessment Group
BLyS B-​lymphocyte stimulator (see also BAFF)
BMC bone mineral content
BMD bone mineral density
BMI body mass index
BSR British Society of Rheumatology
BVAS Birmingham Vasculitis Activity Score
C cervical (e.g. C6 is the sixth cervical vertebra)
CA coracoacromial
CADM clinically amyopathic dermatomyositis
CAMPS CARD14-​mediated psoriasis
CANDLE chronic atypical neutrophilic dermatosis with lipodystrophy
and elevated temperature
cAPS catastrophic antiphospholipid syndrome
CAPS cryopyrin-​associated periodic fever syndromes
xiv SYMBOLS AND ABBREVIATIONS

CARD caspase activation and recruitment domain

CBT cognitive and behavioural therapy
CCP cyclic citrullinated peptide
CDAI Clinical Disease Activity Index
CHB congenital heart block
CHCC Chapel Hill Consensus Conference
CINCA chronic, infantile, neurological, cutaneous, and articular
syndrome
CK creatine kinase
CKD chronic kidney disease
CMC(J) carpometacarpal (joint)
CMP comprehensive metabolic panel
CMV cytomegalovirus
CNO chronic non-​bacterial osteomyelitis
CNS central nervous system
COMP cartilage oligomeric matrix protein
COX cyclooxygenase
CPP calcium pyrophosphate
CPPD calcium pyrophosphate deposition
CREST calcinosis, Raynaud’s, (o)esophageal dysmotility,
sclerodactyly, telangiectasia (syndrome)
CRMO chronic recurrent multifocal osteomyelitis
CRP C-​reactive protein
CRPS complex regional pain syndrome
CS congenital scoliosis
CSF cerebrospinal fluid
CT computed tomography
CTX collagen X-​link
cTnC cardiac troponin C
cTnT cardiac troponin T
CTS carpal tunnel syndrome
CWP chronic widespread pain
CXR chest radiograph
CYC cyclophosphamide
DAS Disease Activity Score
dcSScl diffuse cutaneous systemic sclerosis
DIC diffuse intravascular coagulation
DILE drug-​induced lupus erythematosus
DIP(J) distal interphalangeal (joint)
DIRA deficiency of IL-​1 receptor agonist
DISH diffuse idiopathic skeletal hyperostosis
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 Microbiology - Study Plan
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Date: July 28, 2025

Exercise 1: Key terms and definitions

Learning Objective 1: Literature review and discussion
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Learning Objective 2: Ethical considerations and implications
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Learning Objective 3: Theoretical framework and methodology
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Learning Objective 4: Study tips and learning strategies
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Learning Objective 5: Current trends and future directions
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Learning outcomes and objectives
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Important: Practical applications and examples
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Historical development and evolution
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Experimental procedures and results
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Theoretical framework and methodology
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Methodology 2: Experimental procedures and results
Important: Interdisciplinary approaches
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Problem-solving strategies and techniques
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Practical applications and examples
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Fundamental concepts and principles
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 14: Diagram/Chart/Graph]
Note: Case studies and real-world applications
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 15: Diagram/Chart/Graph]
Key Concept: Experimental procedures and results
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 16: Diagram/Chart/Graph]
Key Concept: Ethical considerations and implications
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Critical analysis and evaluation
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 18: Diagram/Chart/Graph]
Key Concept: Learning outcomes and objectives
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Example 19: Fundamental concepts and principles
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Results 3: Historical development and evolution
Definition: Interdisciplinary approaches
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Assessment criteria and rubrics
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Remember: Statistical analysis and interpretation
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Critical analysis and evaluation
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Literature review and discussion
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 25: Diagram/Chart/Graph]
Key Concept: Interdisciplinary approaches
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Assessment criteria and rubrics
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Case studies and real-world applications
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Theoretical framework and methodology
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Critical analysis and evaluation
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Background 4: Critical analysis and evaluation
Remember: Learning outcomes and objectives
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Note: Historical development and evolution
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Comparative analysis and synthesis
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Study tips and learning strategies
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 34: Diagram/Chart/Graph]
Key Concept: Historical development and evolution
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 35: Diagram/Chart/Graph]
Key Concept: Key terms and definitions
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 36: Diagram/Chart/Graph]
Note: Experimental procedures and results
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 37: Diagram/Chart/Graph]
Note: Research findings and conclusions
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Experimental procedures and results
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Practice Problem 39: Ethical considerations and implications
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 40: Diagram/Chart/Graph]
Methodology 5: Statistical analysis and interpretation
Example 40: Best practices and recommendations
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 41: Diagram/Chart/Graph]
Important: Problem-solving strategies and techniques
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 42: Diagram/Chart/Graph]
Remember: Key terms and definitions
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Important: Comparative analysis and synthesis
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Theoretical framework and methodology
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 45: Diagram/Chart/Graph]
Practice Problem 45: Key terms and definitions
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Definition: Learning outcomes and objectives
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 47: Literature review and discussion
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Important: Interdisciplinary approaches
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Statistical analysis and interpretation
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Background 6: Current trends and future directions
Note: Critical analysis and evaluation
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Practice Problem 51: Historical development and evolution
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Interdisciplinary approaches
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 53: Diagram/Chart/Graph]
Example 53: Research findings and conclusions
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 54: Diagram/Chart/Graph]
Important: Historical development and evolution
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Comparative analysis and synthesis
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Statistical analysis and interpretation
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Critical analysis and evaluation
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 58: Diagram/Chart/Graph]
Remember: Ethical considerations and implications
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Best practices and recommendations
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
[Figure 60: Diagram/Chart/Graph]
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