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Contributors
Abby G. Abelson, MD Amjid Ashraf Ali, MB ChB, FRCS(Trauma & Dana P. Ascherman, MD
Clinical Assistant Professor of Medicine Orthopaedics) Professor of Medicine
Chair Consultants Shoulder and Elbow Surgeon University of Pittsburgh School of Medicine
. In ion T
Department of Rheumatic and Immunologic Diseases Trauma and Orthopaedics Pittsburgh, Pennsylvania
ed er s IN
Cleveland Clinic Lerner College of Medicine at Case Sheffield Teaching Hospitals Chapter 156, Clinical features, classification, and
Western Reserve University Sheffield, United Kingdom epidemiology of inflammatory muscle disease
Cleveland, Ohio Chapter 80, The elbow
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Sergei P. Atamas, MD, PhD
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Chapter 202, Management of osteoporosis
Kavitta B. Allem, MD Executive Director, Research
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Mary Abraham, MD, MBA Physician Discovery and Preclinical Development
Assistant Professor Division of Rheumatology Corbus Pharmaceuticals, Inc.
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Rheumatology Scripps Clinic/Scripps Green Hospital Norwood, Massachusetts
Department of Internal Medicine La Jolla, California Chapter 8, Principles of adaptive immunity
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NYU Langone Chapter 65, Immunosuppressive agents:
Manhattan, New York cyclosporine, cyclophosphamide, azathioprine, Timothy J. Atkinson, PharmD
Chapter 21, Precision medicine and mycophenolate mofetil, and tacrolimus Clinical Pharmacy Specialist
pharmacogenomics in rheumatology Pain Management
Mohammed Almehthel, MD, FRCPC, ABIM
ig 20 ith OT
Steven B. Abramson, MD
Professor of Internal Medicine
Department of Medicine
Clinical Associate Professor
Medicine
University of British Columbia
Pharmacy Service
VA Tennessee Valley Healthcare System
Murfreesboro, Tennessee
Chapter 60, Principles of pharmacologic pain
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Professor ht 2 ou Vancouver, British Columbia, Canada management
Department of Pathology Chapter 48, Dual x-ray absorptiometry and
Chair of the Department of Medicine measurement of bone Maha A. Azeez, MB BCh BAO, BSc, MD, MRCPI
,
ig se ES
Vice Dean for Education Consultant Rheumatologist

Faculty and Academic Affairs Mohammed Almohaya, MD, MHSc Oxford University Hospitals NHS Foundation Trust
NYU Grossman School of Medicine Endocrinologist Nuffield Department of Orthopaedics
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New York, New York Obesity, Endocrine and Metabolism Center Rheumatology and Musculoskeletal Sciences
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Chapter 22, The microbiome in rheumatic King Fahad Medical City University of Oxford
diseases Riyadh, Saudi Arabia Oxford, United Kingdom
op er A
Al ht s
Chapter 48, Dual x-ray absorptiometry and Chapter 70, Tumor necrosis factor inhibitors
Jonathan D. Adachi, BSc, MD, FRCPC
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measurement of bone
Actavis Chair in Rheumatology for Better Bone Alan N. Baer, MD, FACP, MACR
©
Health Elena Riera Alonso, MD Professor of Medicine

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Professor Rheumatologyst Division of Rheumatology

Department of Medicine Division of Rheumatology Johns Hopkins University
McMaster University Hospital Mútua Terrassa Director
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Michael G. DeGroote School of Medicine Barcelona, Spain Jerome L. Greene Sjögren’s Syndrome Center
Hamilton, Ontario, Canada Chapter 173, Adult-onset Still disease Baltimore, Maryland
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Chapter 203, Glucocorticoid-induced osteoporosis Chapter 146, Sjögren syndrome

Mary-Carmen Amigo, MD, FACP, MACR,
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Rohit Aggarwal, MD M Bioeth Xenofon Baraliakos, MD, PhD

Professor of Medicine Professor Professor
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University of Pittsburgh School of Medicine, Rheumatology Service Rheumatology

Pittsburgh, Pennsylvania American British Cowdray (ABC) Medical Center Rheumazentrum Ruhrgebiet Herne
Chapter 156, Clinical features, classification, Mexico City, Mexico Ruhr-University Bochum
and epidemiology of inflammatory muscle Chapter 147, Antiphospholipid syndrome: Bochum, Germany
disease pathogenesis, diagnosis, and management Chapter 124, Imaging in spondyloarthritis
Shizuo Akira, MD, PhD Martin Aringer, MD Thomas Bardin, MD

Professor Professor of Medicine (Rheumatology) Emeritus Professor of Rheumatology
Laboratory of Host Defense Department of Medicine III Université de Paris
WPI Immunology Frontier Research Center Division of Rheumatology Paris, France
Osaka University University Medical Center and Faculty of Medicine Chapter 215, Miscellaneous arthropathies
Osaka, Japan Carl Gustav Carus at the TU Dresden
Chapter 7, Principles of innate immunity Dresden, Germany Leslie Barnsley, B.Med.Hons, Grad.Dip.Epi., PhD,
Chapter 9, Signal transduction in immune cells FRACP, FAFRM(RACP)
Daniel Aletaha, MD, MSc, MBA Senior Staff Specialist
Professor and Head Elizabeth V. Arkema, ScM, ScD Department of Rheumatology
Division of Rheumatology Associate Professor Concord Hospital
Medical University of Vienna Department of Medicine Solna Associate Professor
Vienna, Austria Karolinska Institutet Medicine
Chapter 99, Assessment of the patient with Stockholm, Sweden Sydney University
rheumatoid arthritis and the measurement of Chapter 23, Principles of epidemiology Sydney, New South Wales, Australia
outcomes Chapter 175, Sarcoidosis Chapter 77, Neck pain
vii
viii CONTRIBUTORS
Andrew J. Barr, MBBS, PhD, MRCP Francis Berenbaum, MD, PhD Markus Böhm, MD
Consultant Rheumatologist Professor of Rheumatology Professor
Leeds Teaching Hospitals NHS Trust AP-HP Saint-Antoine Hospital Dermatology
Leeds, United Kingdom Sorbonne Université—INSERM University of Münster
Chapter 187, Imaging of osteoarthritis Paris, France Münster, Germany
Chapter 191, Emerging treatments for Chapter 34, The skin in rheumatic disease
Joan M. Bathon, MD osteoarthritis
Professor of Medicine Michael Bonelli, Assoc. Prof, Priv. Doz, Dr.
Chief Brian Berman, MD Division of Rheumatology
Division of Rheumatology Professor Emeritus of Family and Community Department of Internal Medicine III
Columbia University Irving Medical Center/ Medicine Medical University of Vienna
New York Presbyterian Hospital University of Maryland School of Medicine Vienna, Austria
New York, New York Baltimore Maryland Chapter 9, Signal transduction in immune cells
Chapter 101, Management of rheumatoid arthritis Chapter 56, Complementary and alternative
in patients with prior exposure to conventional medicine Dimitrios T. Boumpas, MD, FACP
. In ion T
synthetic disease-modifying antirheumatic drugs
Professor of Medicine
Bonnie L. Bermas, MD 4th Department of Internal Medicine
ed er s IN
(csDMARDs)
Professor of Medicine Attikon University Hospital and Joint Academic
Jill J.F. Belch, MBChB, MD (Hons), FRCP, FRS Division of Rheumatic Diseases Rheumatology Program
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UT Southwestern Medical Center National and Kapodistrian University of Athens
c. .
Professor of Vascular Medicine
Division of Clinical and Molecular Medicine Dallas, Texas Medical School
se se rm P
Ninewells Hospital and Medical School Chapter 59, Medication management during Affiliated Investigator
Dundee, United Kingdom preconception, pregnancy, and lactation Immunobiology
re El pe R
Chapter 154, Raynaud phenomenon
Biomedical Research Foundation of the Academy of
Alice Elizabeth Berry, PhD, MSc, BSc Athens
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Research Fellow Athens, Greece
Teresita Bellido, PhD
Faculty of Health and Applied Sciences Chapter 144, Management of renal lupus
Professor and Chair
University of the West of England
Department of Physiology and Cell Biology
Bristol, United Kingdom Aline Bozec, PhD
Professor
Chapter 54, Multidisciplinary approaches to Professor of Rheumatology and Immunology
ig 20 ith OT
Department of Internal Medicine
Division of Endocrinology
Department of Orthopedic Surgery
University of Arkansas for Medical Sciences
managing chronic pain in arthritis
George Bertsias, MD, PhD

Department of Internal Medicine 3
Friedrich Alexander University (FAU)
Erlangen, Germany
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Associate Professor of Rheumatology and Clinical Chapter 13, Osteoimmunology
Little Rock, Arkansas
ht 2 ou
Chapter 3, Bone structure and function
Immunology
Medical School University of Crete Richard D. Brasington, Jr., MD
,
Herakleio, Greece Emeritus Professor of Medicine and Ophthalmology

ig se ES
Ami Ben-Artzi, MD and Visual Sciences

Chapter 144, Management of renal lupus
Division of Rheumatology Division of Rheumatology
Cedars-Sinai Medical Center Suleman Bhana, MD, FACR Washington University School of Medicine in
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Los Angeles, California

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Senior Medical Director, Rheumatology St. Louis

Chapter 93, Imaging of rheumatoid arthritis Inflammation & Immunology, North America St. Louis, Missouri
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Medical Affairs Chapter 90, Clinical features of rheumatoid arthritis

Fabrizio Benedetti, MD Pfizer, Inc.
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Professor Jürgen Braun, Prof.Dr.

New York, New York
Department of Neuroscience Elisabethgruppe
Chapter 180, The epidemiology of coronavirus
©
University of Turin Medical School

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disease 2019 (COVID-19) and rheumatic Rheumazentrum Ruhrgebiet

Turin, Italy Ruhr-University Bochum
disease
Director Herne, NRW, Germany
Medicine & Physiology of Hypoxia Shamik Bhattacharyya, MD, MS Chapter 124, Imaging in spondyloarthritis
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Plateau Rosà, Switzerland Physician

Chapter 55, Placebo, nocebo, caring, and healing Neurology Elisabeth Brouwer, MD, PhD
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in rheumatology Brigham and Women’s Hospital Professor

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Department of Rheumatology and Clinical

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Harvard Medical School

Kim L. Bennell, BAppSci(physio), PhD Boston, Massachusetts Immunology
Professor of Physiotherapy
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Chapter 40, The nervous system in rheumatic University Medical Center Groningen
Director disease University of Groningen
Centre for Health, Exercise & Sports Medicine Groningen, The Netherlands
University of Melbourne Yelda Bilginer, MD Chapter 162, Biology and immunopathogenesis of
Melbourne, Australia Hacettepe University vasculitis
Chapter 53, Principles of rehabilitation: physical and Ankara, Turkey
occupational therapy Chapter 169, IgA vasculitis (Henoch–Schönlein Jacques P. Brown, MD, FRCPC
purpura) Clinical Professor of Medicine
Sarah E. Bennett, PhD, MSc, BSc Medicine
Research Associate Jane F. Bleasel, MBBS, PhD, MHPE, FRACP Université Laval
Faculty of Health and Applied Sciences Professor Senior Clinical Researcher
University of the West of England Sydney Medical School Rheumatology
Bristol, United Kingdom University of Sydney CHU de Québec-Université Laval
Chapter 54, Multidisciplinary approaches to Sydney, Australia Quebec City, Quebec, Canada
managing chronic pain in arthritis Chapter 210, Hemophilia-associated arthritis Chapter 205, Paget disease of bone
Roberta A. Berard, MD, FRCPC, MSc Joel A. Block, MD Matthew A. Brown, MBBS, MD, FRACP, FAHMS, FAA
Associate Professor The Willard L Wood MD Professor and Director Chief Scientific Officer
Pediatrics Division of Rheumatology Genomics England
Western University Rush University Medical Center Professor of Medicine
London, Ontario, Canada Chicago, Illinois King’s College London
Chapter 107, Management of juvenile idiopathic Chapter 183, Clinical features of osteoarthritis London, United Kingdom
arthritis Chapter 122, Genetics of axial spondyloarthritis
CONTRIBUTORS ix
Matthew L. Brown, MD Joel N. Buxbaum, MD Ricard Cervera, MD, PhD, FRCP

Cooper University Hospital Professor Molecular Medicine Emeritus Head of the Department of Autoimmune
Camden, New Jersey The Scripps Research Institute Diseases
Chapter 82, The hip La Jolla, California Hospital Clínic
Chapter 177, The systemic amyloidoses Professor of Medicine
Maya H. Buch, MBChB, FRCP, PhD University of Barcelona
Professor of Rheumatology Vivian P. Bykerk, MD Barcelona, Catalonia, Spain
Centre for Musculoskeletal Research Professor of Medicine Chapter 142, Management of nonrenal and
Division of Musculoskeletal and Dermatological Weill Cornell Medical College non–central nervous system lupus
Sciences Cornell University
School of Biological Sciences Rheumatologist Christopher Chang, MD, PhD, MBA
Faculty of Biology Hospital for Special Surgery Professor of Medicine
Medicine & Health New York, New York Division of Rheumatology, Allergy and Clinical
The University of Manchester Chapter 64, Synthetic disease-modifying Immunology
Manchester, United Kingdom antirheumatic drugs and leflunomide University of California, Davis
. In ion T
Honorary Professor of Rheumatology Davis, California
Leeds Institute of Rheumatic & Musculoskeletal Cassandra Calabrese, DO
ed er s IN
Medical Director
Medicine Physician Division of Pediatric Immunology and Allergy
Faculty of Medicine & Health Rheumatologic and Immunologic Diseases Joe DiMaggio Children’s Hospital
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c. .
University of Leeds Physician Hollywood, Florida
Leeds, United Kingdom Infectious Disease Professor of Pediatrics
se se rm P
Chapter 100, Management of rheumatoid arthritis in Cleveland Clinic Foundation Pediatrics
csDMARD-naïve patients Cleveland, Ohio Florida Atlantic University
re El pe R
Chapter 179, Immune-mediated complications of Boca Raton, Florida
Christopher D. Buckley, MBBS, DPhil
checkpoint inhibitors Professor of Pediatrics
Kennedy Professor of Translational Rheumatology
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Pediatrics
Kennedy Institute of Rheumatology Leonard H. Calabrese, DO Florida International University
University of Oxford Roosevelt Drive Professor of Medicine Miami, Florida
Headington Oxford Cleveland Clinic Lerner College of Medicine Chapter 87, Complex regional pain syndrome
Chapter 1, The synovium
ig 20 ith OT
William D. Bugbee, MD
Attending Physician
Case Western Reserve University
Vice Chairman
Department of Rheumatic and Immunological
Diseases
Joyce C. Chang, MD, MSCE
Assistant Professor of Pediatrics
Division of Immunology
Department of Orthopaedic Surgery
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R.J. Fasenmyer Chair of Clinical Immunology Boston Children’s Hospital and Harvard Medical
Scripps Clinic
ht 2 ou Theodore F. Classen DO Chair of Osteopathic School
La Jolla, California
,
Chapter 82, The hip

Research and Education Boston, Massachusetts
ig se ES
Cleveland Clinic Foundation Chapter 109, Systemic autoimmune rheumatic

Gerd-Rüdiger Burmester, MD Cleveland, Ohio diseases in children
Professor of Medicine Chapter 113, Viral infections
Benjamin C. Chaon, MD
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Immunology Jeffrey P. Callen, MD Assistant Professor
Professor of Medicine (Dermatology) Uveitis and Ocular Immunology
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Charité-Universitätsmedizin Berlin
Al ht s
Berlin, Germany Chief Johns Hopkins University Wilmer Eye Institute

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Chapter 30, Laboratory tests in rheumatic disorders Division of Dermatology Baltimore, Maryland
University of Louisville School of Medicine Chapter 35, Ocular manifestations of rheumatic
©
Jane C. Burns, MD Louisville, Kentucky diseases

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Professor of Pediatrics Chapter 170, Cutaneous vasculitis and panniculitis

Director Prateek Chaudhary, DO
Kawasaki Disease Research Center Andrew J. Carr, DSc, MA, ChM, FRCS Colorado Center for Arthritis and Osteoporosis LLC
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University of California San Diego School of Nuffield Professor of Orthopaedic Surgery Longmont, Colorado
Medicine Head Nuffield Department of Orthopaedics, Chapter 145, Systemic lupus erythematosus in
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La Jolla, California Rheumatology & Musculoskeletal Sciences pregnant patients and neonatal lupus
University of Oxford
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Director
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Kawasaki Disease Clinic Oxford, United Kingdom Hyon K. Choi, MD, DrPH
Chapter 4, Tendons and ligaments Professor of Medicine
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Rady Children’s Hospital-San Diego

San Diego, California Division of Rheumatology, Allergy and
Chapter 168, Kawasaki disease John A. Carrino, MD, MPH Immunology
Professor Harvard Medical School
David B. Burr, PhD Radiology Professor of Medicine
Distinguished Professor Emeritus Weil Cornell Medicine Department of Medicine
Anatomy, Cell Biology and Physiology Vice-Chairman Director
Indiana University School of Medicine Radiology & Imaging Gout and Crystal Arthropathy Center
Distinguished Professor Emeritus Hospital for Special Surgery Director
Biomedical Engineering New York, New York Clinical Epidemiology and Health Outcomes
Indiana University-Purdue University, Indianapolis Chapter 208, Osteonecrosis Massachusetts General Hospital
(IUPUI) Boston, Massachusetts
Indianapolis, Indiana Sabrina Cavallo, BSc (OT), MSc, PhD Chapter 192, Epidemiology and classification
Chapter 3, Bone structure and function Assistant Professor of gout
Occupational Therapy Program
Frank Buttgereit, MD Université de Montréal Researcher Ernest H.S. Choy, MD, FRCP
Professor of Rheumatology Centre for Interdisciplinary Research in Professor of Rheumatology
Charité University Medicine Berlin Rehabilitation of Greater Montreal Institut CREATE Centre
Department of Rheumatology and Clinical Universitaire sur la Réadaptation en Déficience Section of Rheumatology
Immunology Physique de Montréal School of Medicine
Berlin, Germany Montréal, Québec, Canada Cardiff University
Chapter 62, Systemic glucocorticoids in Chapter 110, Rehabilitation and psychosocial issues Cardiff, United Kingdom
rheumatology in juvenile idiopathic arthritis Chapter 72, Inhibitors of T-cell costimulation
x CONTRIBUTORS
Lisa Christopher-Stine, MD, MPH Deputy Director Vivette D. D’Agati, MD
Associate Professor of Medicine (Rheumatology) National Institute for Health Research Professor of Pathology
and Neurology Leeds Biomedical Research Centre Columbia University College of Physicians and Surgeons
Director Leeds, United Kingdom Director
Johns Hopkins Myositis Center Chapter 187, Imaging of osteoarthritis Renal Pathology Laboratory
Johns Hopkins University School of Medicine Columbia University Medical Center
Baltimore, Maryland Cyrus Cooper, FMedSci New York, New York
Chapter 160, Metabolic, drug-induced, and other Professor and Director Chapter 136, Immunopathology of systemic lupus
noninflammatory myopathies MRC Lifecourse Epidemiology Unit erythematosus
University of Southampton
Lorinda Chung, MD, MS Southampton, United Kingdom David I. Daikh, MD, PhD
Professor of Medicine and Dermatology Chapter 198, Epidemiology and classification of Professor of Medicine
Division of Immunology and Rheumatology osteoporosis Division of Arthritis and Rheumatic Diseases
Stanford University School of Medicine Oregon Health and Science University
Palo Alto, California Wendy Costello Attending PhysicianDivision of Hospital and
. In ion T
Chapter 158, Clinical significance of autoantibodies Irish Children’s Arthritis Network (iCAN) Specialty Medicine
in inflammatory muscle disease Chapter 180, The epidemiology of coronavirus Portland VA Health Care System
ed er s IN
disease 2019 (COVID-19) and rheumatic Portland, Oregon
Francesco Ciccia, MD, PhD disease Chapter 137, Animal models of systemic lupus
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Full Professor
c. .
erythematosus
Department of Precision Medicine Karen H. Costenbader, MD, MPH
se se rm P
Rheumatology Unit Lupus Program Director Stephanie G. Dakin, PhD, BVetMed, MRCVS
University of the studies of Campania “Luigi Division of Rheumatology, Immunology and Associate Professor of Musculoskeletal Sciences
Allergy
re El pe R
Vanvitelli” Nuffield Department of Orthopaedics,
Naples, Italy Brigham and Women’s Hospital Rheumatology & Musculoskeletal Sciences
s 3. t FO
Chapter 166, Polymyalgia rheumatica and giant cell University of Oxford
arteritis Harvard Medical School Oxford, United Kingdom
Boston, Massachusetts Chapter 4, Tendons and ligaments
Daniel J. Clauw, MD Chapter 132, Epidemiology and classification of
Professor of Anesthesiology systemic lupus erythematosus Nicola Dalbeth, MBChB, MD, FRACP
Director ig 20 ith OT
Medicine (Rheumatology) and Psychiatry
Chronic Pain and Fatigue Research Center

George L.D. Cox, BMedSci, BMBS, MD, FRCS(T&O)
Consultant
Professor and Rheumatologist
University of Auckland
Department of Trauma & Orthopaedics
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University of Michigan Medical School
ht 2 ou Auckland, New Zealand
Ann Arbor, Michigan University Hospital Southampton Chapter 193, Etiology and pathogenesis of gout
Chapter 88, Fibromyalgia and related syndromes Southampton, United Kingdom
,
Chapter 79, The shoulder Aileen M. Davis, PhD

ig se ES
Jacqui Clinch, MBBS, MRCP, FRCPCH Professor

Consultant in Paediatric Rheumatology Paul Creamer, MD, FRCP Institute of Health Policy, Management and
Paediatric Rheumatology Consultant and Senior Clinical Lecturer EvaluationProfessor
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Bristol Royal Hospital for Children Department of Rheumatology Department of Physical Therapy
Bristol, United Kingdom North Bristol Trust University of Toronto
op er A
Bristol, United Kingdom Toronto, Ontario, Canada

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Consultant in Paediatric Pain

Bath Centre for Pain Services Chapter 207, Neuropathic arthropathy Chapter 188, Assessment of the patient with
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Royal National Hospital for Rheumatic Diseases osteoarthritis and measurement of outcomes
Bruce N. Cronstein, MD
©
Bath, United Kingdom

David P. D’Cruz, MD, FRCP
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Chapter 217, Hypermobility syndrome Paul R. Esserman Professor of Medicine

Division of Rheumatology Consultant Rheumatologist
Megan E.B. Clowse, MD, MPH New York University School of Medicine The Louise Coote Lupus Unit
New York, New York Guy’s Hospital
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Associate Professor of Medicine

Division of Rheumatology and Immunology Chapter 21, Precision medicine and London, United Kingdom
pharmacogenomics in rheumatology Chapter 36, The cardiovascular system in rheumatic
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Duke University Medical Center

disease
Durham, North Carolina
o
Raymond K. Cross, MD, MS

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Chapter 145, Systemic lupus erythematosus in Carlos Eduardo de Barros Branco, MD

pregnant patients and neonatal lupus Professor of Medicine
Researcher
o
Medicine
Valvular Heart Disease Unit
John (Gerry) Coghlan, MD, FRCP University of Maryland School of Medicine
Heart Institute—University of São Paulo Medical
Consultant Cardiologist Baltimore, Maryland
School
Cardiology Chapter 38, The gastrointestinal tract in rheumatic
São Paulo, Brazil
Royal Free Hospital disease
Chapter 115, Acute rheumatic fever
London, United Kingdom
Chapter 36, The cardiovascular system in rheumatic Jeffrey R. Curtis, MD, MS, MPH Berber de Boer, MD
disease Harbert-Ball Professor of Medicine Resident
Division of Clinical Immunology & Rheumatology Rheumatology
Robert A. Colbert, MD, PhD University of Alabama at Birmingham LUMC
Senior Investigator Birmingham, Alabama Leiden, The Netherlands
National Institute of Arthritis, Musculoskeletal and Chapter 92, Common comorbidities in rheumatoid Chapter 69, Interleukin-6 inhibitors
Skin Diseases arthritis
National Institutes of Health Ann-Sophie De Craemer, MD
Bethesda, Maryland Chris D’Adamo, PhD Faculty of Medicine and Health Sciences
Chapter 106, Etiology and pathogenesis of juvenile Director Department of Internal Medicine and Pediatrics
idiopathic arthritis Center for Integrative Medicine Ghent University
Assistant Professor Department of Rheumatology
Philip G. Conaghan, MBBS, PhD, FRACP, FRCP Department of Family and Community Medicine Ghent University Hospital
Director & Professor of Musculoskeletal Assistant Professor of Epidemiology and Public Molecular Immunology and Inflammation Unit
Medicine Health VIB Center for Inflammation Research
Leeds Institute of Rheumatic and Musculoskeletal University of Maryland School of Medicine Ghent, Belgium
Medicine Baltimore, Maryland Chapter 121, Pathogenesis and pathophysiology of
University of Leeds Chapter 56, Complementary and alternative medicine axial spondyloarthritis
CONTRIBUTORS xi
Adriana A. de Jesus, MD, PhD Edward F. DiCarlo, MD Paul Emery, MD, MA, FMedSci, FRCP
Staff Scientist Attending Pathologist Versus Arthritis
Translational Autoinflammatory Diseases Department of Pathology and Laboratory Medicine Professor of Rheumatology
Section Hospital for Special Surgery Leeds Institute of Rheumatic and Musculoskeletal
NIAID, NIH Professor of Clinical Pathology and Laboratory Medicine
Bethesda, Maryland Medicine University of Leeds
Chapter 174, Monogenic autoinflammatory Cornell University Medical College Director
diseases New York, New York NIHR Leeds Biomedical Research Centre
Chapter 185, Pathogenesis and pathology of Leeds Teaching Hospital NHS Trust
Salvatore De Vita, MD osteoarthritis Leeds, United Kingdom
Professor of Rheumatology Chapter 73, Inhibitors of B cells
Department of Medicine Oliver Distler, Prof., Dr.
University of Udine University Hospital Zurich Max R. Emmerling, MD, DDS
Chief Department of Rheumatology Attending in Oral & Maxillofacial Surgery
Rheumatology Clinic University of Zurich Cook County Health
. In ion T
Hospital S. Maria della Misericordia Zurich, Switzerland Chicago, Illinois
Chapter 153, Emerging therapies for systemic sclerosis
ed er s IN
Udine, Italy Chapter 85, The temporomandibular joint
Chapter 171, Cryoglobulinemia Pamela Donlan, PT, DPT, EdD, CLT-LANA
Gerard Espinosa, MD, PhD
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Assistant Clinical Professor
c. .
Maarten de Wit, PhD Department of Autoimmune Diseases
Bouve College of Health Sciences
Hospital Clínic
se se rm P
Independent Patient Researcher Department of Physical Therapy, Movement and
Centre for Patient Education Associate Professor of Medicine
Rehabilitation Sciences
Stichting Tools University of Barcelona
Northeastern University
re El pe R
Amsterdam, The Netherlands Barcelona, Catalonia, Spain
Boston, Massachusetts
Chapter 50, The patient perspective Chapter 142, Management of nonrenal and
Chapter 52, Arthritis patient education,
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non–central nervous system lupus
self-management, and health promotion
Chad L. Deal, MD Luis R. Espinoza†, MD
Associate Professor of Medicine Tracy J. Doyle, MD, MPH
Division of Pulmonary and Critical Care Medicine Professor and Chief
Cleveland Clinic Lerner College of Medicine at Case
Head ig 20 ith OT
Western Reserve University
Center for Osteoporosis and Metabolic Bone

Brigham and Women’s Hospital
Chapter 37, The lungs in rheumatic disease
Rheumatology Section
LSU Health Science Center
Louisiana State University
New Orleans, Louisiana
N
Disease ht 2 ou Hannah du Preez, BA (Hons), MA (Cantab.), BM Chapter 112, Mycobacterial, brucellar, fungal, and
Rheumatology Department of Radiology parasitic arthritis
Cleveland Clinic
,
St Bartholomew’s Hospital
Cleveland, Ohio
ig se ES
Barts Health NHS Trust Stephen Eyre, PhD

Chapter 202, Management of osteoporosis Professor
Chapter 211, Rheumatologic manifestations of Division of Musculoskeletal and Dermatological
Kevin D. Deane, MD, PhD
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hemoglobinopathies Sciences
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Professor of Medicine The University of Manchester

Division of Rheumatology George S.M. Dyer, MD Manchester, United Kingdom
op er A
Al ht s
University of Colorado School of Medicine Associate Professor of Orthopaedic Surgery Chapter 26, Principles of genetic epidemiology
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Aurora, Colorado Department of Orthopaedic Surgery

Chapter 98, Preclinical rheumatoid arthritis Brigham and Women’s Hospital Antonis Fanouriakis, MD
©
Harvard Medical School Assistant Professor of Internal Medicine-Rheumatology

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Paul F. Dellaripa, MD Cambridge Massachusetts Medical School National and Kapodistrian

Associate Professor of Medicine Orthopedic Surgeon University of Athens and Joint Academic
Harvard Medical School Brigham and Women’s Hospital Rheumatology Program
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Division of Rheumatology Boston, Massachusetts Athens, Greece

Brigham and Women’s Hospital Chapter 81, The wrist and hand Chapter 144, Management of renal lupus
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Richard Eastell, MD, FRCP, FRCPath, FMedSci Joshua Farber, MD
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Chapter 37, The lungs in rheumatic disease

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Professor of Bone Metabolism Senior Investigator

Department of Oncology and Metabolism Laboratory of Molecular Immunology, DIR
o
Elaine Dennison, MB, BChir, MSc, FRCP, PhD University of Sheffield National Institute of Allergy and Infectious
Professor of Musculoskeletal Sheffield, South Yorkshire, United Kingdom Diseases
Epidemiology Chapter 201, Biochemical markers of bone turnover National Institutes of Health
MRC Lifecourse Epidemiology Unit in postmenopausal osteoporosis Bethesda, Maryland
Southampton University Chapter 10, Cytokines
Southampton, United Kingdom Jan Ehrchen, Priv. Doz. Dr. med. Dr. rer. nat.
Professor of Clinical Research Department of Dermatology Anders Fasth, MD, PhD
School of Biological Sciences University Hospital of Münster Professor
Victoria University Münster, Germany Department of Pediatrics
Wellington, New Zealand Chapter 34, The skin in rheumatic disease University of Gothenburg
Chapter 198, Epidemiology and classification of Department of Pediatric Immunology
osteoporosis Dirk Elewaut, MD, PhD Senior Consultant
Professor of Rheumatology and Immunology Department of Pediatrics
Christopher P. Denton, PhD, FRCP Ghent University Queen Silvia Children’s Hospital
Professor of Experimental Rheumatology, Chair of the Department of Rheumatology Gothenburg, Sweden
Consultant Rheumatologist Ghent University Hospital Senior Consultant
Centre for Rheumatology Group Leader Servicio de Inmunología y Reumatología
University College London (UCL) Molecular Immunology and Inflammation Unit Pediátrica Hospital Nacional de Niños “Dr. Carlos
Royal Free Hospital VIB Center for Inflammation Research Sáenz Herrera”
London, United Kingdom Ghent, Belgium San José, Costa Rica
Chapter 149, Clinical and serologic features of Chapter 121, Pathogenesis and pathophysiology of Chapter 105, Clinical features of juvenile idiopathic
systemic sclerosis axial spondyloarthritis arthritis
†
Deceased.
xii CONTRIBUTORS
Eugen Feist, MD Lindsy Forbess, MD, MSc Nophar Geifman, PhD, MSc
Professor Assistant Professor of Medicine Professor
Rheumatology Division of Rheumatology School of Health Sciences
Helios-Clinic Cedars-Sinai Medical Center Faculty of Health and Medical Sciences
Gommern, Germany Los Angeles, California University of Surrey
Chapter 30, Laboratory tests in rheumatic disorders Chapter 93, Imaging of rheumatoid arthritis Guildford, United Kingdom
Chapter 163, Polyarteritis nodosa and Cogan Chapter 16, Big Data analysis
Candace H. Feldman, MD, MPH, ScD syndrome
Division of Rheumatology, Inflammation and Michael D. George, MD, MSCE
Immunity David A. Fox, MD Assistant Professor
Associate Physician Professor of Medicine Medicine
Brigham and Women’s Hospital Division of Rheumatology University of Pennsylvania
Assistant Professor of Medicine University of Michigan Medical School Assistant Professor
Harvard Medical School Ann Arbor, Michigan Biostatistics Epidemiology and Informatics
Boston, Massachusetts Chapter 71, Interleukin-17, interleukin-12, and University of Pennsylvania
. In ion T
Chapter 132, Epidemiology and classification of interleukin-23 inhibitors Philadelphia, Pennsylvania
Chapter 92, Common comorbidities in rheumatoid
ed er s IN
systemic lupus erythematosus
Tracy M. Frech, MD, MS arthritis
Ruth Fernandez-Ruiz, MD, MS Internal Medicine
M. Eric Gershwin, MD
rv vi is R
c. .
Post-doctoral Fellow Vanderbilt University Medical Center
Division of Rheumatology Nashville Tennessee Chief
se se rm P
Department of Medicine Adjunct Division of Rheumatology, Allergy and Clinical
NYU Grossman School of Medicine University of Utah Immunology
Internal Medicine
re El pe R
New York, New York Salt Lake City, Utah
Chapter 11, Inflammation and its chemical Chapter 152, Management of systemic University of California
Davis, California
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mediators sclerosis
Chapter 87, Complex regional pain syndrome
Andrew Filer, MBChB, PhD Elisa Frisaldi, PhD Jay Ghadiali, MD
Reader, Institute of Inflammation and Ageing Research Fellow in Neurophysiology Fellow
ig 20 ith OT
The University of Birmingham
Honorary Consultant Rheumatologist
Department of Rheumatology
University Hospitals Birmingham NHS Foundation
Neuroscience Department
University of Turin Medical School
Turin, Italy
Chapter 55, Placebo, nocebo, caring, and healing in
Rheumatology
University of Pennsylvania Perelman School of
Medicine
Philadelphia, Pennsylvania
N
Trust ht 2 ou rheumatology
Chapter 185, Pathogenesis and pathology of
Birmingham, United Kingdom osteoarthritis
Chapter 1, The synovium Cem Gabay, MD
,
ig se ES
Professor of Medicine Elisabeth Gilis, PhD

David F. Fiorentino, MD, PhD Head Faculty of Medicine and Health Sciences
Professor Division of Rheumatology Department of Internal Medicine and Pediatrics
w
Dermatology University Hospitals of Geneva Ghent University

yr u G
Stanford University School of Medicine Geneva, Switzerland Department of Rheumatology, Molecular

Redwood City, California Chapter 68, Interleukin-1 inhibitors Immunology and Inflammation Unit
op er A
Al ht s
Chapter 158, Clinical significance of autoantibodies VIB Center for Inflammation Research
Massimo Gadina, PhD
C th P
in inflammatory muscle disease Ghent, Belgium

Chief Chapter 121, Pathogenesis and pathophysiology of
Benjamin A. Fisher, MD(res), MBBS
©
Translational Immunology Section axial spondyloarthritis

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Senior Clinical Lecturer National Institute of Arthritis and Musculoskeletal

Rheumatology Research Group and Skin Diseases Deborah T. Gold, MEd, PhD
Institute of Inflammation and Ageing National Institutes of Health Professor Emerita of Medical Sociology
N MP
University of Birmingham Bethesda, Maryland Psychiatry & Behavioral Sciences

Honorary Consultant Rheumatologist Chapter 10, Cytokines Sociology
lr
Department of Rheumatology Duke University Medical Center

University Hospitals Birmingham Saviana Gandolfo, MD Durham, North Carolina
o
SA
NHS Trust Clinic of Rheumatology Chapter 199, Clinical evaluation and clinical features
Birmingham, The United Kingdom Department of Medicine of osteoporosis
o
Chapter 67, Overview of biologic agents Udine University Hospital S. Maria della
Misericordia Garry E. Gold, MD
John D. Fisk, PhD Udine, Italy Professor of Radiology
Psychologist Chapter 171, Cryoglobulinemia Radiology
Seniors Health Stanford School of Medicine
Nova Scotia Health Authority Daniela Garelick, MBBS, BSc Stanford, California
Associate Professor Dr Chapter 44, Magnetic resonance imaging
Psychiatry Rheumatology
Assistant Professor Sheba Medical Center Raphaela Goldbach-Mansky, MD, MHS
Medicine Ramat Gan, Israel Senior Investigator
Adjunct Professor Chapter 211, Rheumatologic manifestations of Translational Autoinflammatory Diseases Section
Psychology & Neuroscience hemoglobinopathies NIH
Dalhousie University Bethesda, Maryland
Halifax, Nova Scotia, Canada Steffen Gay, MD Chapter 174, Monogenic autoinflammatory diseases
Chapter 143, Management of central nervous Professor Emeritus of Experimental
system lupus Rheumatology José A. Gómez-Puerta, MD, PhD, MPH
Senior Consultant Head of the Department of Rheumatology
Martin F. Flajnik, PhD Center of Experimental Rheumatology Hospital Clínic
Professor Department of Rheumatology Associate Professor of Medicine
Microbiology and Immunology University Hospital of Zurich University of Barcelona
University of Maryland Baltimore University of Zurich Barcelona, Catalonia, Spain
Baltimore, Maryland Zurich, Switzerland Chapter 142, Management of nonrenal and
Chapter 8, Principles of adaptive immunity Chapter 20, Epigenetics non–central nervous system lupus
CONTRIBUTORS xiii
Susan M. Goodman, MD Ahmet Gül, MD Philip J. Hashkes, MD, MSc

Attending Physician Professor of Medicine Head
Division of Rheumatology Department of Internal Medicine Pediatric Rheumatology Unit
Hospital for Special Surgery Division of Rheumatology Department of Pediatrics
Professor of Medicine Istanbul University Shaare Zedek Medical Center
Department of Medicine Istanbul Faculty of Medicine Associate Professor of Pediatrics
Weill Cornell Medical School Istanbul, Turkey Hebrew University Hadassah School of Medicine
New York, New York Chapter 167, Behçet disease Jerusalem, Israel
Chapter 57, Outcomes and perioperative management of Chapter 107, Management of juvenile idiopathic
patients with inflammatory arthritis and systemic lupus Rao P. Gullapalli, PhD arthritis
erythematosus undergoing total joint arthroplasty Professor and Associate Vice Chair for Research
Department of Diagnostic Radiology & Nuclear Sarfaraz A. Hasni, MD, MSc
Caroline Gordon, MD, MA, FRCP Medicine Director
Emeritus Professor of Rheumatology University of Maryland School of Medicine Lupus Clinical Research
Rheumatology Research Group Baltimore, Maryland National Institute of Arthritis, Musculoskeletal, and
. In ion T
Institute of Inflammation and Ageing Chapter 45, Functional magnetic resonance imaging Skin Diseases
University of Birmingham National Institutes of Health
ed er s IN
Birmingham, United Kingdom Monica Guma, MD, PhD Bethesda, Maryland
Chapter 67, Overview of biologic agents Associate Professor Chapter 41, The muscles in rheumatic disease
rv vi is R
Medicine
c. .
Sharon Gordon, DDS, MPH, PhD UCSD Andrew Bassim Hassan, DPhil, FRCP
se se rm P
Associate Dean for Academic Affairs and Research La Jolla, California Head
Kansas City University College of Dental Medicine Chapter 129, Etiology and pathogenesis of psoriatic Sarcoma and TYA Oncology Unit
Kansas City, Missouri arthritis
re El pe R
NHS Department of Oncology
Chapter 85, The temporomandibular joint Oxford Haematology and Cancer Centre
Sarthak Gupta, MD
s 3. t FO
Laure Gossec, MD, PhD Assistant Research Physician Oxford University Hospitals Trust
Professor Lupus Clinical Trials Unit Professor of Medical Oncology
Rheumatology National Institute of Arthritis and Musculoskeletal Sir William Dunn School of Pathology
Sorbonne Université and Skin Diseases University of Oxford
INSERM
ig 20 ith OT
Institut Pierre Louis d’Epidémiologie et de Santé
Publique
Paris France
National Institutes of Health
Bethesda, Maryland
Chapter 139, Pathogenesis of systemic lupus
Oxford, United Kingdom
Chapter 218, Bone tumors
Lukas Haupt, MD
erythematosus
N
AP-HP
ht 2 ou Department of Rheumatology
Pitié-Salpêtrière Hospital Shuhong Han, PhD Hietzing Hospital
Division of Rheumatology, Allergy, & Clinical Vienna, Austria
,
Rheumatology Department
ig se ES
Immunology Appendix: Classification and diagnostic criteria

Paris, France
Chapter 127, Clinical features of psoriatic arthritis University of Florida College of Medicine
Gainesville, Florida Jonathan S. Hausmann, MD
Andrew J. Grainger, BM, BS, FRCR, FRCP Program in Rheumatology
w
Chapter 138, Autoantibodies in systemic lupus

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Consultant Radiologist erythematosus Boston Children’s Hospital

Cambridge University Hospitals NHS Foundation Trust Division of Rheumatology and Clinical
op er A
Al ht s
Cambridge, United Kingdom John G. Hanly, MD, FRCP(C) Immunology

Professor of Medicine and Pathology Beth Israel Deaconess Medical Center
C th P
Chapter 187, Imaging of osteoarthritis

Dalhousie University and Queen Elizabeth II Harvard Medical School
Rebecca Grainger, MBChB, BmedSci, PhD
©
Health Sciences Center Boston, Massachusetts

LE
University of Otago Halifax, Nova Scotia, Canada Chapter 180, The epidemiology of coronavirus
Wellington, New Zealand Chapter 143, Management of central nervous system disease 2019 (COVID-19) and rheumatic
Chapter 180, The epidemiology of coronavirus lupus disease
N MP
disease 2019 (COVID-19) and rheumatic disease

Eric P. Hanson, MD Gillian A. Hawker, MD, MSc
Ellen M. Gravallese, MD Associate Professor
lr
Theodore Bevier Bayles Professor of Medicine Professor of Medicine

Pediatrics, Microbiology and Immunology and Division of Rheumatology
o

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Medical and Molecular Genetics University of Toronto

Chief Indiana University School of Medicine Chair of Medicine
o
Division of Rheumatology, Inflammation and Indianapolis, Indiana

Immunity University of Toronto
Chapter 9, Signal transduction in immune cells Toronto, Ontario, Canada
Boulos Haraoui, MD, FRCPC Chapter 188, Assessment of the patient with
Associate Professor of Medicine osteoarthritis and measurement of outcomes
Chapter 97, Pathogenesis and pathology of Université de Montréal
Turid Heiberg, PhD
rheumatoid arthritis Montreal, Quebec, Canada
Regional Research Support
Chapter 64, Synthetic disease-modifying
Jeffrey D. Greenberg, MD, MPH Oslo University Hospital
antirheumatic drugs and leflunomide
Assistant Professor of Medicine Oslo, Norway
Division of Rheumatology John B. Harley, MD, PhD Chapter 102, Multidisciplinary nonpharmacologic
New York University School of Medicine Principal Investigator approach to rheumatoid arthritis
New York, New York Research Service
Chapter 21, Precision medicine and US Department of Veterans Affairs (USDVA) Simon M. Helfgott, MD, CM
pharmacogenomics in rheumatology Medical Center and Cincinnati Education and Associate Professor of Medicine
Research for Veterans Foundation Medicine
Luiza Guilherme Guglielmi, PhD Cincinnati, Ohio Harvard Medical School
Professor of Immunology Chapter 135, Genetics of systemic lupus erythematosus Director of Education & Fellowship Training
Heart Institute—InCor Division of Rheumatology
University of São Paulo School of Medicine Tayseer G. Haroun Brigham and Women’s Hospital
Institute for Immunology Investigation Northern Virginia Center for Arthritis Boston, Massachusetts
National Institute for Science and Technology Reston, Virginia Chapter 209, Rheumatoid manifestations
São Paulo, Brazil Chapter 145, Systemic lupus erythematosus in of endocrine and metabolic diseases and
Chapter 115, Acute rheumatic fever pregnant patients and neonatal lupus treatments
xiv CONTRIBUTORS
Rana S. Hinman, BPhysio, PhD Robert D. Inman, MD Douglas A. Jabs, MD, MBA
Professor of Physiotherapy Professor of Medicine and Immunology Director
Centre for Health Exercise & Sports Medicine University of Toronto Faculty of Medicine Center for Clinical Trials and Evidence
University of Melbourne Schroeder Arthritis Institute Synthesis
Melbourne, Australia University Health Network Professor of Epidemiology
Chapter 53, Principles of rehabilitation: physical and Professor of Medicine The Johns Hopkins Bloomberg School of Public
occupational therapy Medicine Health
University of Toronto Professor of Ophthalmology
Anna-Maria Hoffmann-Vold, MD, PhD Toronto, Ontario, Canada The Wilmer Eye Institute
Department of Rheumatology The Johns Hopkins University School
Chapter 116, Reactive arthritis
Oslo University Hospital of Medicine
Oslo, Norway Baltimore, Maryland
Chapter 153, Emerging therapies for systemic sclerosis Dai Inoue, MD, PhD
Chapter 35, Ocular manifestations of rheumatic
Assistant Professor
diseases
Christopher R. Holroyd, BM, FRCP, PhD Department of Radiology
. In ion T
Consultant Rheumatologist Kanazawa University Hospital
Ishikawa, Japan Judith A. James, MD, PhD
MRC Lifecourse Epidemiology Unit
ed er s IN
Chapter 178, IgG4-related disease Vice President of Clinical Affairs
University of Southampton
Oklahoma Medical Research Foundation
Southampton, United Kingdom
Oklahoma City, Oklahoma
rv vi is R
Zacharia Isaac, MD
c. .
Chapter 198, Epidemiology and classification of
Associate Vice Provost for Clinical and Translational
osteoporosis Division Chief
se se rm P
Science
Pain and Spine Care Oklahoma University Health Sciences Center
Cathy Holt, BEng, PhD Department of Physical Medicine and Oklahoma City, Oklahoma
re El pe R
Professor of Biomechanics and Orthopaedic Rehabilitation Chapter 133, Preclinical features of systemic lupus
Engineering Harvard Medical School erythematosus
s 3. t FO
School of Engineering Associate Chairman
Cardiff University Physical Medicine and Rehabilitation
Cardiff, Wales Bochra Jandali, MD
Brigham and Women’s Hospital Assistant Professor
Chapter 5, Biomechanics of peripheral joints and spine
Boston, Massachusetts Department of Internal Medicine
ig 20 ith OT
Audra Horomanski, MD
Assistant Professor
Division of Immunology & RheumatologyStanford
Chapter 78, Low back pain
John D. Isaacs, BSc (Hon), MB BS, PhD

University of Texas
Houston, Texas
Chapter 148, Classification and epidemiology of
N
University ht 2 ou Professor of Clinical Rheumatology systemic sclerosis
Stanford, California Translational and Clinical Research Institute
Chapter 158, Clinical significance of autoantibodies Newcastle University M. Kassim Javaid, MBBS, BMedSCI, PhD, FRCP
,
ig se ES
in inflammatory muscle disease Consultant Rheumatologist Associate Professor in Metabolic Bone

Newcastle upon Tyne Hospitals NHS Foundation Disease
Thomas W.J. Huizinga, MD, PhD Trust Botnar Institute of Musculoskeletal Sciences
Professor of Rheumatology Newcastle Upon Tyne, United Kingdom
w
yr u G
Leiden University Medical Center Chapter 74, Emerging therapeutic targets Oxford, United Kingdom
Leiden, The Netherlands Chapter 216, Heritable connective tissue
op er A
Al ht s
Chapter 69, Interleukin-6 inhibitors disorders

David Isenberg, MD, FRCP, FAMS
C th P
Professor
Frances Humby, PhD, MBBS, MRCP Rose-Marie Javier, MD
The Centre for Rheumatology Research
©
Centre for Experimental Medicine and Rheumatology Senior Lecturer

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William Harvey Research Institute Department of Medicine

Professor Rheumatology
Queen Mary University of London Medical University Louis Pasteur
London, United Kingdom Rheumatology/Medicine
University College London Senior Attending Physician
N MP
Chapter 33, Minimally invasive procedures

London, United Kingdom Rheumatology Unit
University Hospital Hautepierre
lr
M. Elaine Husni, MD, MPH Chapter 211, Rheumatologic manifestations of

hemoglobinopathies Strasbourg, France
Staff Physician
o
Chapter 213, Gaucher disease

SA
Orthopedic and Rheumatologic Institute

Vice Chair Maura D. Iversen, BSc, MPH, DPT, SD
o
Department of Rheumatic and Immunologic Diseases Roy Jefferis, BSc, PhD, FRSC, CChem, MRCP,
Professor and Dean FRCPath, DSc
Cleveland Clinic College of Health Professions
Director Professor Emeritus
Sacred Heart University Institute of Immunology & Immunotherapy
Arthritis and Musculoskeletal Center Fairfield, Connecticut
Department of Rheumatic and Immunologic University of Birmingham
Senior Instructor in Medicine Birmingham, The United Kingdom
Diseases Harvard Medical School Chapter 67, Overview of biologic agents
Cleveland, Ohio Behavioral Scientist
Chapter 126, Classification and epidemiology of Section of Clinical Sciences
psoriatic arthritis Matlock A. Jeffries, MD, FACP, FACR
Division of Rheumatology, Inflammation & Associate Member
Immunity Oklahoma Medical Research Foundation
Jonathan Hwang, MD
Brigham & Women’s Hospital Arthritis and Clinical Immunology Program
Michael G. DeGroote School of Medicine
Boston, Massachusetts Interim Section Chief of Rheumatology
McMaster University
Hamilton, Ontario, Canada Professor Emeritus Clinical Associate Professor of Medicine
Chapter 203, Glucocorticoid-induced osteoporosis
Bouve College of Health Sciences Adjunct Clinical Associate Professor of
Department of Physical Therapy, Movement and Microbiology and Immunology
Kimme Hyrich, MD, PhD Rehabilitation Sciences University of Oklahoma Health Sciences Center
Professor Northeastern University Department of Medicine, Division of Rheumatology,
Centre for Musculoskeletal Research Boston, Massachusetts Immunology, and Allergy
University of Manchester Chapter 52, Arthritis patient education, Oklahoma City, Oklahoma
Manchester, United Kingdom self-management, and health Chapter 186, Genetics and epigenetics of
Chapter 16, Big Data analysis promotion osteoarthritis
CONTRIBUTORS xv
Sindhu R. Johnson, MD, PhD Mariana J. Kaplan, MD Jennifer A. Kelly, MPH

Director Senior Investigator and Chief Research Program Director
Toronto Scleroderma Program Systemic Autoimmunity Branch Genes and Human Disease Program
Rheumatology Deputy Scientific DirectorIntramural Research Program Oklahoma Medical Research Foundation
University Health Network National Institute of Arthritis and Musculoskeletal Oklahoma City, Oklahoma
Associate Professor of Medicine and Skin Diseases Chapter 135, Genetics of systemic lupus erythematosus
Associate Director National Institutes of Health
Clinical Epidemiology & Health Care Research Bethesda, Maryland David Kendler, MD
Program Chapter 139, Pathogenesis of systemic lupus Professor of Medicine
Institute of Health Policy, Management & Evaluation erythematosus Medicine
University of Toronto University of British Columbia
Toronto, Ontario, Canada Timothy L. Karr, PhD Vancouver, British Columbia, Canada
Chapter 24, Principles of clinical outcome assessment Associate Research Professor Chapter 48, Dual x-ray absorptiometry and
The Biodesign Institute measurement of bone
Brian Johnstone, PhD Arizona State University
. In ion T
Professor Tempe, Arizona Randall E. Keyser, PhD
Orthopaedics and Rehabilitation Associate Professor
ed er s IN
Chapter 18, Proteomics
Oregon Health & Science University Rehabilitation Science
Portland, Oregon Dimitrios G. Kassimos, MD, MSc, PhD George Mason University
rv vi is R
Consultant Rheumatologist Fairfax, Virginia
c. .
Chapter 2, The articular cartilage
Rheumatology401 General Military Hospital of Athens Chapter 41, The muscles in rheumatic disease
Anna Helena Jonsson, MD, PhD
se se rm P
Athens, Greece
Associate Physician Chapter 207, Neuropathic arthropathy Munther A. Khamashta, MD, PhD, FRCP
Division of Rheumatology, Inflammation, and Emeritus Professor of Medicine
re El pe R
Immunity Daniel L. Kastner, MD, PhD King’s College London
Department of Medicine Scientific Director, Division of Intramural Research
s 3. t FO
Brigham and Women’s Hospital Metabolic, Cardiovascular and Inflammatory GSK-Gulf Medical Expert(Lupus)
Instructor in Medicine Disease Genomics Branch Dubai, United Arab Emirates
Harvard Medical School National Human Genome Research Institute Chapter 147, Antiphospholipid syndrome:
Boston, Massachusetts National Institutes of Health pathogenesis, diagnosis, and management
ig 20 ith OT
Chapter 97, Pathogenesis and pathology of
rheumatoid arthritis
Bethesda, Maryland
Chapter 174, Monogenic autoinflammatory diseases Dinesh Khanna, MD, MS
Andrew A. Joyce, MD Jeffrey N. Katz, MD, MSc
N
ht 2 ou Division of Rheumatology
Assistant Professor Professor of Medicine and Orthopedic Surgery University of Michigan Medical School
University of Utah School of Medicine Orthopedics and Medicine Ann Arbor, Michigan
,
Salt Lake City, Utah Harvard Medical School Chapter 151, Outcomes measures in systemic
ig se ES
Chapter 78, Low back pain Director sclerosis

Orthopedic and Arthritis Center for Outcomes Research
Michelle Jung, MD, FRCPC Department of Orthopedics and Division of Kiran Khokhar, MBBS, BSc, MRCP (UK)
w
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Clinical Assistant Professor Rheumatology, Immunology and Allergy Rheumatology Registrar

Division of Rheumatology Brigham and Women’s Hospital Leeds Institute of Rheumatic and Musculoskeletal
op er A
University of Calgary
Al ht s
Boston, Massachusetts Medicine & NIHR Leeds Biomedical Research Centre

Calgary, Alberta, Canada Chapter 58, Indications for and long-term Leeds, United Kingdom
C th P
Chapter 141, Assessing disease activity and outcome

complications of total hip and knee arthroplasty Chapter 187, Imaging of osteoarthritis
in systemic lupus erythematosus
©
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Mitsuhiro Kawano, MD, PhD David Kiefer, MD

Ruba Kado, MD
Professor Mr.
Clinical Instructor in Internal Medicine
Department of Rheumatology Rheumazentrum Ruhrgebiet
Division of Rheumatology
N MP
Graduate School of Medical Science Herne

University of Michigan Medical School
Kanazawa University Germany
Ann Arbor, Michigan
lr
Ishikawa, Japan Mr.

Chapter 71, Interleukin-17, interleukin-12, and
Chapter 178, IgG4-related disease Rheumatology
o
interleukin-23 inhibitors
SA
Ruhr-University Bochum
Tsuneyasu Kaisho, MD, PhD Jonathan Kay, MD Bochum, Germany
o
Professor Timothy S. and Elaine L. Peterson Chair in Rheumatology Chapter 124, Imaging in spondyloarthritis
Department of Immunology Professor of Medicine and of Population and
Institute of Advanced Medicine Quantitative Health Sciences Lauren K. King, MD, MSc
Wakayama Medical University Division of Rheumatology Rheumatologist
Wakayama, Japan Department of Medicine Medicine
Chapter 7, Principles of innate immunity
Division of Epidemiology St. Michael’s Hospital
Department of Population and Quantitative Health Unity Health Toronto
Natasha Kamal, MD Sciences Clinician Scientist Trainee
University of Maryland School of Medicine UMass Chan Medical School and UMass Memorial Medicine
GastroenterologyInternal Medicine Medical Center University of Toronto
Baltimore, Maryland Worcester, Massachusetts Toronto, Ontario, Canada
Chapter 38, The gastrointestinal tract in rheumatic Chapter 75, Biosimilars in rheumatology Chapter 188, Assessment of the patient with
disease Chapter 215, Miscellaneous arthropathies osteoarthritis and measurement of outcomes
David Kane, PhD, FRCPI Richard M. Keating, MD, MHS Margreet Kloppenburg, MD, PhD
Clinical Professor of Rheumatology Associate Program Director, Rheumatology Fellowship Professor
Department of Rheumatology Division of Rheumatology Department of Rheumatology
Trinity College Dublin Scripps Clinic/Scripps Green Hospital Professor
Consultant Rheumatologist La Jolla, California Clinical Epidemiology
Tallaght University Hospital Chapter 65, Immunosuppressive agents: Leiden University Medical Center
Dublin, Ireland cyclosporine, cyclophosphamide, azathioprine, Leiden, The Netherlands
Chapter 46, Musculoskeletal ultrasonography mycophenolate mofetil, and tacrolimus Chapter 190, Management of osteoarthritis
xvi CONTRIBUTORS
Sharon L. Kolasinski, MD Jay I. Lakkis, MD Ronald M. Laxer, MDCM, FRCPC
Professor of Clinical Medicine Assistant Professor in Clinical Medicine Professor of Pediatrics and Medicine
Division of Rheumatology Weill Cornell Medicine–New York-Presbyterian Division of Rheumatology
University of Pennsylvania Hospital University of Toronto Faculty of Medicine
Philadelphia, Pennsylvania New York, New York Toronto, Ontario, Canada
Chapter 190, Management of osteoarthritis Chapter 39, The kidneys in rheumatic diseases Chapter 107, Management of juvenile idiopathic
arthritis
Kathleen D. Kolstad, MD, PhD Robert B.M. Landewé, MD, PhD
Clinical Instructor Professor of Clinical Immunology & Suzanne C. Li, MD, PhD
Department of Medicine Rheumatology Professor of Pediatrics
Division of Rheumatology Amsterdam University Medical Center Division of Pediatric Rheumatology
University of California Los Angeles Academic Medical Center Joseph M. Sanzari Children’s Hospital
Los Angeles, California Amsterdam Hackensack Meridian School of Medicine
Chapter 158, Clinical significance of autoantibodies The Netherlands Hackensack, New Jersey
in inflammatory muscle disease Consultant Rheumatologist Chapter 109, Systemic autoimmune rheumatic
. In ion T
Zuyderland Medical Center diseases in children
Leah C. Kottyan, PhD
ed er s IN
Heerlen, The Netherlands
Associate Professor and Interim Director Chapter 27, Interpreting the medical literature for the Katherine P. Liao, MD, MPH
Center for Autoimmune Genomics and rheumatologist Associate Professor of Medicine and Biomedical
rv vi is R
c. .
Etiology Chapter 49, Use of imaging as an outcome measure Informatics
Cincinnati Children’s Hospital Medical Center in clinical trials Harvard Medical School
se se rm P
Cincinnati, Ohio Division of Rheumatology, Inflammation, and
Chapter 135, Genetics of systemic lupus Carol A. Langford, MD, MHS Immunity
re El pe R
erythematosus Director Brigham and Women’s Hospital
Center for Vasculitis Care and Research Rheumatology Section and the Massachusetts
s 3. t FO
Virginia Byers Kraus, MD, PhD Harold C. Schott Chair in Rheumatic and Veterans Epidemiology Research and Information
Mary Bernheim Distinguished Professor of Immunologic Diseases Center
Medicine Cleveland Clinic VA Boston Healthcare System
Adjunct Professor of Orthopaedics and Professor of Medicine Boston, Massachusetts
Pathology
ig 20 ith OT
Duke Molecular Physiology Institute
Duke University School of Medicine
Durham, North Carolina
Cleveland Clinic Lerner College of Medicine of
Case Western Reserve University
Cleveland, Ohio
Chapter 165, Takayasu arteritis
rheumatoid arthritis
Scott M. Lieberman, MD, PhD

N
Chapter 189, Preclinical and early osteoarthritis Associate Professor
ht 2 ou Marciana L. Laster, MD, MSCR Division of Rheumatology, Allergy & Immunology
Leo R.W. Kronberger, MD
,
Assistant Professor Pediatrics Stead Family Department of Pediatrics

ig se ES
Orthopedic Department David Geffen School of Medicine at UCLA Carver College of Medicine
Balgrist University Hospital Los Angeles, California University of Iowa
Orthopedic Clinic Chapter 204, Osteomalacia, rickets, and renal Iowa City, Iowa
w
Schulthess Clinic osteodystrophy Chapter 109, Systemic autoimmune rheumatic

yr u G
Zurich, Switzerland diseases in children

Chapter 111, Bacterial native joint arthritis Augustin Latourte, MD, PhD
op er A
Al ht s
Assistant Professor Jean W. Liew, MD, MS

Jeffrey M. Kroopnick, MD
C th P
Rheumatologist Section of Rheumatology

Division of Endocrinology Rheumatology Department of Medicine
©
Diabetes and Nutrition Hôpital Lariboisière Boston University School of Medicine

LE
Department of Medicine Paris, France Boston, Massachusetts

University of Maryland School of Medicine Chapter 212, Hemochromatosis Chapter 180, The epidemiology of coronavirus
Baltimore, Maryland disease 2019 (COVID-19) and rheumatic disease
N MP
Chapter 200, Pathophysiology of osteoporosis Arthur N. Lau, MD, MSc, FRCPC

Associate Professor Geoffrey O. Littlejohn, MBBS(Hons), MD, MPH
lr
Tore K. Kvien, MD, PhD Department of Medicine Clinical Professor of Medicine

Professor Emeritus of Rheumatology McMaster University Monash University
o
SA
University of Oslo Faculty of Medicine Hamilton, Ontario, Canada Emeritus Director

Department of Rheumatology Chapter 203, Glucocorticoid-induced osteoporosis Monash Rheumatology
o
Division of Rheumatology and Research Monash Medical Centre

Diakonhjemmet Hospital Viktoryia Laurynenka, PhD Clayton, Victoria, Australia
Oslo, Norway Research Associate Chapter 206, Diffuse idiopathic skeletal
Chapter 102, Multidisciplinary nonpharmacologic Center for Autoimmune Genomics and hyperostosis
approach to rheumatoid arthritis Etiology
Cincinnati Children’s Hospital Medical Center Eva S. Liu, MD
Joshua LaBaer, MD, PhD Cincinnati, Ohio Assistant Professor of Medicine
Executive Director, Biodesign Institute Chapter 135, Genetics of systemic lupus Harvard Medical School
Director, Virginia G. Piper Center for Personalized erythematosus Division of Endocrinology
Diagnostics Brigham and Women’s Hospital
Professor, School of Molecular Sciences Robert A. Lavin, MD, MS Boston, Massachusetts
Arizona State University Associate Professor Chapter 204, Osteomalacia, rickets, and renal
Tempe, Arizona Neurology osteodystrophy
Chapter 18, Proteomics University of Maryland School of Medicine
Director of Chronic Pain Management Lawrence Lo, MD
Robert Lafyatis, MD Department of Neurology Division of Musculoskeletal Imaging and
Thomas Medsger, Professor of Medicine VA Maryland Health Care System Intervention
Division of Rheumatology and Clinical Adjunct Professor Department of Radiology
Immunology Department of Occupational Medicine Brigham and Women’s Hospital
University of Pittsburgh Medical Center Johns Hopkins University School of Medicine Harvard Medical School
Pittsburgh, Pennsylvania Baltimore, Maryland Boston, Massachusetts
Chapter 150, Etiology and pathogenesis of systemic Chapter 60, Principles of pharmacologic pain Chapter 43, Conventional radiography and
sclerosis management computed tomography
CONTRIBUTORS xvii
Rik J. Lories, MD, PhD Anne-Marie Malfait, MD, PhD Maureen D. Mayes, MD, MPH
Full Professor The George W Stuppy, MD, Chair of Arthritis, and Professor of Medicine
Skeletal Biology and Engineering Research Center Professor Division of Rheumatology
KU Leuven and Division of Rheumatology Division of Rheumatology University of Texas Health Science Center
University Hospitals Leuven Rush University Medical Center Houston
Leuven, Belgium Chicago, Illinois McGovern School of Medicine
Chapter 130, Animal models of psoriatic arthritis Chapter 183, Clinical features of osteoarthritis Houston, Texas
Thomas A. Luger, MD Tamir Malley, MRCP systemic sclerosis
Professor of Dermatology Specialist Registrar in Rheumatology
Department of Dermatology Rheumatology Department Timothy McAlindon, MD, MPH, MRCP
University of Münster Nuffield Orthopaedic Centre Professor of Medicine
Münster, Germany Oxford, United Kingdom Tufts University School of Medicine
Chapter 34, The skin in rheumatic disease Chapter 164, Antineutrophil cytoplasm Chief
antibody–associated vasculitis Division of Rheumatology
. In ion T
Ingrid E. Lundberg, MD, PhD Tufts Medical Center
Professor of Rheumatology Boston, Massachusetts
ed er s IN
Julia Manasson, MD
Division of Rheumatology Instructor Chapter 208, Osteonecrosis
Department of Medicine, Solna Medicine
rv vi is R
Karolinska Institutet Edward F. McCarthy, MD
c. .
Stockholm, Sweden NYU Grossman School of Medicine Professor of Pathology and Orthopaedic Surgery
se se rm P
Chapter 157, Etiology and pathogenesis of
New York, New York Pathology
inflammatory muscle disease (myositis)
Chapter 22, The microbiome in rheumatic
Johns Hopkins University School of Medicine
re El pe R
diseases
Baltimore, Maryland
Raashid A. Luqmani, B Med Sci, BM, BS, DM, Chapter 218, Bone tumors
FRCP, FRCPE
s 3. t FO
Professor of Rheumatology Lyn M. March, AM, MBBS, MSc (Epidemiology), Geraldine M. McCarthy, MD
Nuffield Department of Orthopaedics, PhD, FRACP, FAFPHM Mater Misericordiae University Hospital
Rheumatology and Musculoskeletal Science Liggins Professor of Rheumatology and School of Medicine
University of Oxford Musculoskeletal Epidemiology University College Dublin
Rheumatology ig 20 ith OT
Consultant Rheumatologist
Nuffield Orthopaedic Centre

University of Sydney and Kolling Institute
Professorial Rheumatology Department
Royal North Shore Hospital
St Leonards, New South Wales, Australia
Dublin, Ireland
Chapter 197, Basic calcium phosphate crystal
deposition disease
N
Chapter 51, Treatment recommendations and Michael F. McDermott, MB, BCh, BAO, MRCPI,
ht 2 ou
Chapter 164, Antineutrophil cytoplasm
“treat to target”
antibody–associated vasculitis DMed
,
Professor of Experimental Rheumatology

ig se ES
Pedro M. Machado, FRCP, PhD Alejandro Olivé Marqués, MD, PhD University of Leeds—St James’s University
Centre for Rheumatology & Department of Rheumatology Service Hospital
Neuromuscular Diseases Rheumatology National Institute of Health Research—Leeds
w
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University College London Hospital Universitari Germans Trias i Pujol Musculoskeletal Biomedical Research Unit
Department of Rheumatology & Queen Square Badalona Leeds Institute of Rheumatic and Musculoskeletal
op er A
Centre for Neuromuscular Diseases Barcelona, Spain

Al ht s
Medicine
University College London Hospitals NHS Chapter 173, Adult-onset Still disease Leeds, United Kingdom
C th P
Foundation Trust Chapter 174, Monogenic autoinflammatory

Department of Rheumatology Javier Márquez, MD, MSc diseases
©
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Northwick Park Hospital Rheumatologist

London North West University Healthcare NHS Trust Department of Internal Medicine Patrick J. McDonnell, JD
London, United Kingdom Hospital Pablo Tobon Uribe Principal
Chapter 180, The epidemiology of coronavirus Litigation
N MP
Medellin, Antioquia, Colombia

disease 2019 (COVID-19) and rheumatic disease Chapter 112, Mycobacterial, brucellar, fungal, and Law Offices of McDonnell & Associates
King of Prussia, Pennsylvania
lr
parasitic arthritis
Klaus P. Machold, MD Chapter 87, Complex regional pain syndrome
o
Associate Professor of Internal Medicine

SA
Paul Martin, PhD, MPhil, BSc

Department of Rheumatology Research Fellow Versus Arthritis Dennis McGonagle, PhD, FRCPI
o
Medical University of Vienna Centre for Musculoskeletal Research Professor of Investigative Rheumatology
Vienna, Austria University of Manchester Leeds Institute of Rheumatic & Musculoskeletal
Chapter 32, Synovial fluid analysis
Manchester, United Kingdom Medicine
Chapter 16, Big Data analysis
University of Leeds
C. Ronald MacKenzie, MD Leeds, United Kingdom
Attending Physician Chapter 118, Enthesopathies
Department of Rheumatology and Medicine Manuel Martínez-Lavín, MD
Chapter 129, Etiology and pathogenesis of psoriatic
C. Ronald MacKenzie Chair in Ethics and Medicine Chief
arthritis
Hospital for Special Surgery Rheumatology Department
Professor of Clinical Medicine and Medical Ethics National Institute of Cardiology Alexa Simon Meara, MD, MS
Department of Medicine and Medical Ethics Professor of Rheumatology Assistant Professor
Weill Cornell Medicine National Autonomous University Internal Medicine
New York, New York Mexico City, Mexico The Ohio State University
Chapter 57, Outcomes and perioperative Chapter 214, Digital clubbing and hypertrophic Columbus, Ohio
management of patients with inflammatory osteoarthropathy Chapter 179, Immune-mediated complications of
arthritis and systemic lupus erythematosus checkpoint inhibitors
undergoing total joint arthroplasty Eric L. Matteson, MD, MPH
Professor Emeritus of Medicine Jay J. Mehta, MD, MSEd
Tanya J. Major, PhD, BSc(Hons), BA Divisions of Rheumatology and Associate Professor of Clinical Pediatrics
Post-Doctoral Fellow Epidemiology Pediatric Rheumatology
Department of Biochemistry Mayo Clinic College of Medicine and Science Children’s Hospital of Philadelphia
University of Otago Rochester, Minnesota Philadelphia, Pennsylvania
Dunedin, New Zealand Chapter 91, Extraarticular features of rheumatoid Chapter 109, Systemic autoimmune rheumatic
Chapter 193, Etiology and pathogenesis of gout arthritis diseases in children
xviii CONTRIBUTORS
Andrew R. Melville, MA, MSc, MBBS, MRCP Jonathan J. Miner, MD, PhD Esperanza Naredo, MD, PhD
Clinical Research Fellow Associate Professor of Medicine Department of Rheumatology
Institute of Infection Immunity & Inflammation Division of Rheumatology Bone and Joint Research Unit
University of Glasgow Perelman School of Medicine at the University of Hospital Universitario Fundación Jiménez Díaz and
Glasgow, Scotland Pennsylvania Universidad Autónoma de Madrid
Chapter 100, Management of rheumatoid arthritis in Philadelphia, Pennsylvania Madrid, Spain
csDMARD-naïve patients Chapter 90, Clinical features of rheumatoid Chapter 31, Aspiration and injection of joints and
Chapter 154, Raynaud phenomenon arthritis periarticular tissue and intralesional therapy
Joseph F. Merola, MD, MMSc Deeba Minhas, MD Victoria Navarro-Compán, MD, PhD
Associate Professor Clinical Lecturer Rheumatology Department
Dermatology Rheumatology University Hospital La Paz
Brigham and Women’s Hospital University of Michigan IdiPaz, Madrid, Spain
Boston, Massachusetts Ann Arbor Chapter 120, Clinical features of axial
Chapter 128, Extraarticular manifestations and Michigan spondyloarthritis
. In ion T
comorbidities in psoriatic arthritis Chapter 88, Fibromyalgia and related syndromes
Barbara Neerinckx, MD, PhD, prof dr
ed er s IN
Robert G. Micheletti, MD Rikke Helene Moe, PhD, PT, MSc Rheumatology
Associate Professor of Dermatology and Medicine Researcher University Hospitals Leuven/Skeletal Biology and
rv vi is R
Perelman School of Medicine National Advisory Unit on Rehabilitation in Engineering Center KU Leuven
c. .
University of Pennsylvania Rheumatology Leuven, Belgium
se se rm P
Philadelphia, Pennsylvania Diakonhjemmet Hospital Chapter 123, Animal models of spondyloarthritis
Chapter 170, Cutaneous vasculitis and panniculitis Division of Rheumatology and Research Chapter 130, Animal models of psoriatic arthritis
re El pe R
Oslo, Norway
Laëtitia Michou, MD, PhD Amanda E. Nelson, MD, MSCR
Chapter 102, Multidisciplinary nonpharmacologic
Associate Professor of Medicine Associate Professor of Medicine
s 3. t FO
approach to rheumatoid arthritis
Université Laval Division of Rheumatology, Allergy, and Immunology
Endocrinology and Nephrology Unit Ingrid Möller, MD, PhD and Thurston Arthritis Research Center
CHU de Quebec Research Centre Instituto Poal de Reumatología University of North Carolina at Chapel Hill
Quebec City, Quebec, Canada Human Anatomy and Embryology Unit Chapel Hill, North Carolina
ig 20 ith OT
Chapter 205, Paget disease of bone
Rob Middleton, BM BCh, MA(Cantab), MRCS

Department of Experimental Pathology and
Therapeutics
Faculty of Medicine
Chapter 181, Epidemiology and classification of
osteoarthritis
Alessandra Nerviani, MD, PhD

Academic Clinical Fellow
N
ht 2 ou Bellvitge Campus Centre for Experimental Medicine and
Nuffield Department of Orthopaedics University of Barcelona
Rheumatology and Musculoskeletal Sciences Rheumatology
Barcelona, Spain
,
University of Oxford William Harvey Research Institute

Chapter 31, Aspiration and injection of joints
ig se ES
Oxford, United Kingdom Queen Mary University of London

and periarticular tissue and intralesional
Chapter 83, The knee
therapy
Chapter 33, Minimally invasive procedures
w
Disha Midha, BM, BCom, BSc, Diploma in

yr u G
Renuka Mopuru, MD Philippa J.A. Nicolson, BPhty, PhD

Innovation Management Assistant Professor Versus Arthritis Foundation Fellow
op er A
Dr
Al ht s
Department of Ophthalmology and Visual Nuffield Department of Orthopaedics,

Cardiology Sciences Rheumatology and Musculoskeletal Sciences
C th P
Royal Free London NHS Foundation Trust University of Texas Medical Branch University of Oxford
London, United Kingdom Galveston, Texas
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Chapter 36, The cardiovascular system in rheumatic Chapter 35, Ocular manifestations of rheumatic Chapter 53, Principles of rehabilitation: physical and
disease diseases occupational therapy
Jamal A. Mikdashi, MD, MPH, MBA Parisa Mortaji, BS, MD Ellen B. Nordal, MD, PhD
N MP
Associate Professor of Medicine Department of Medicine Senior Consultant

Division of Rheumatology and Clinical Immunology University of Colorado
lr
Department of Pediatrics
University of Maryland School of Medicine Aurora, Colorado University Hospital of Northern NorwayAssociate
o
Baltimore, Maryland
SA
Chapter 98, Preclinical rheumatoid arthritis Professor

Chapter 172, Primary angiitis of the central nervous
Department of Clinical Medicine
Alisa A. Mueller, MD, PhD
o
system
University of Tromsø
Rheumatology Fellow Tromsø, Norway
Frederick W. Miller, MD, PhD Division of Rheumatology, Inflammation and Chapter 105, Clinical features of juvenile idiopathic
Scientist Emeritus Immunity arthritis
Environmental Autoimmunity Group Brigham and Women’s Hospital
Clinical Research Branch Harvard Medical School Ulrich Nöth, MD
National Institute of Environmental Health Sciences Boston, Massachusetts Professor and Director
National Institutes of Health Chapter 63, Methotrexate Department of Orthopaedics and Trauma Surgery
Durham, North Carolina Evangelisches Waldkrankenhaus Spandau
Chapter 159, Management of inflammatory muscle Elena Myasoedova, MD, PhD Berlin, Germany
disease Associate Professor of Internal Medicine Chapter 15, Principles of tissue engineering and
Division of Rheumatology cell- and gene-based therapy
Kirsten Minden, MD Mayo Clinic College of Medicine and Science
Professor of Health Services Research Rochester, Minnesota Eleana Ntatsaki, MRCP (Rheumatology) (UK), MA,
Program Area Epidemiology and Health Services Chapter 91, Extraarticular features of rheumatoid MedED, FHEA
Research arthritis Consultant Rheumatologist
Deutsches Rheuma-Forschungszentrum Berlin Department of Rheumatology
Consultant in Pediatric Rheumatology Gauthier Namur, MD Ipswich Hospital
Charité Universitätsmedizin Berlin Dr Ipswich, United Kingdom
Department of Pediatric Respiratory Medicine Department of Nuclear Medicine Honorary Senior Clinical Lecturer
Immunology and Critical Care Medicine Centre Hospitalier Chrétien University College London Medical School
Berlin, Germany Liège, Belgium London, United Kingdom
Chapter 104, Classification and epidemiology of Chapter 47, Bone scintigraphy and positron emission Chapter 161, Classification and epidemiology of
juvenile idiopathic arthritis tomography vasculitis
CONTRIBUTORS xix
Tilman Obenhuber, MD Gisela Orozco, PhD Carlo Patrono, MD

Division of Infectious Diseases and Hospital Dr Professor of Pharmacology
Epidemiology Division of Musculoskeletal and Dermatological Catholic University School of Medicine
University Hospital Zurich Sciences Rome, Italy
Zurich, Switzerland The University of Manchester Chapter 61, Nonsteroidal antiinflammatory
Internal Medicine Manchester, United Kingdom drugs
Hospital Zollikerberg Chapter 26, Principles of genetic epidemiology
Zollikerberg, Switzerland Lourdes M. Perez-Chada, MD, MMSc
Chapter 111, Bacterial native joint arthritis Carl Orr, MB, BCh, BAO, MRCPI, BMedSci, MSc, Psoriasis and Psoriatic Arthritis Clinical Research
LMD, PhD Fellow
Chester V. Oddis, MD Consultant Rheumatologist Dermatology
Professor of Medicine St Vincent’s University Hospital and University Brigham and Women’s Hospital
Division of Rheumatology and Clinical Immunology College Dublin Boston, Massachusetts
University of Pittsburgh School of Medicine Dublin, Ireland Chapter 128, Extraarticular manifestations and
Pittsburgh, Pennsylvania Chapter 131, Management of psoriatic arthritis comorbidities in psoriatic arthritis
. In ion T
Chapter 156, Clinical features, classification, and
epidemiology of inflammatory muscle disease
ed er s IN
John J. O’Shea, MD Luc Pijnenburg, MD
Scientific Director Rheumatology
Alexis R. Ogdie-Beatty, MD, MSCE Medical University Louis Pasteur
National Institute of Arthritis and Musculoskeletal
rv vi is R
Associate Professor of Medicine
c. .
and Skin Diseases Attending Physician
Hospital of the University of Pennsylvania Rheumatology Unit
se se rm P
Associate Professor of Epidemiology in Biostatistics University Hospital Hautepierre
Bethesda, Maryland
and Epidemiology Strasbourg, France
Chapter 9, Signal transduction in immune cells
re El pe R
Philadelphia, Pennsylvania Chapter 213, Gaucher disease
Chapter 10, Cytokines
s 3. t FO
psoriatic arthritis
Caroline Ospelt, MD, PhD Michael H. Pillinger, MD
Ahmed Omar, MBBCh, MRCP, MSc Professor of Experimental Rheumatology Professor of Medicine and Biochemistry and
Staff Physician Center of Experimental Rheumatology Molecular Pharmacology
Mount Sinai Hospital Department of Rheumatology Division of Rheumatology
ig 20 ith OT
Toronto, Ontario, Canada
Chapter 116, Reactive arthritis
University Hospital of Zurich
University of Zurich
Zurich, Switzerland
NYU Grossman School of Medicine
Section Chief
Rheumatology
Chapter 20, Epigenetics
N
Michael J. Ombrello, MD VA New York Harbor Health Care System
ht 2 ou New York Campus
Principal Investigator Monika Østensen, MD
,
National Institute of Arthritis and Musculoskeletal Professor U.S. Department of Veterans Affairs
ig se ES
and Skin Diseases Consultant New York, New York

National Institutes of Health Rheumatology Chapter 11, Inflammation and its chemical
Bethesda, Maryland Department of Rheumatology Sorlandet sykehus mediators
w
yr u G
Chapter 17, Principles and techniques in molecular biology Kristiansand

Kristiansand, Norway Carlos Pineda, MD, PhD
op er A
Antonina Omisade, PhD General Director

Al ht s
Chapter 59, Medication management during

Psychologist preconception, pregnancy, and lactation Instituto Nacional de Rehabilitación
C th P
Acquired Brain Injury Mexico City, Mexico

Queen Elizabeth II Health Sciences Centre Seza Özen, MD Chapter 214, Digital clubbing and hypertrophic
©
LE
Halifax, Nova Scotia, Canada Professor osteoarthropathy

Chapter 143, Management of central nervous
Pediatrics
system lupus Nicolò Pipitone, MD, PhD
Hacettepe University Faculty of Medicine
Rheumatology Unit
N MP
Karen B. Onel, MD Ankara, Turkey

Chapter 169, IgA vasculitis (Henoch–Schönlein
Chief Azienda Ospedaliera ASMN
lr
purpura)
Division of Pediatric Rheumatology Istituto di Ricovero e Cura a Carattere
o
Hospital for Special Surgery (HSS)

SA
Scientifico
Professor of Clinical Pediatrics Elizabeth Park, MD Reggio Emilia, Italy
Instructor
o
Weill Cornell Medicine Chapter 166, Polymyalgia rheumatica and giant cell
New York, New York Division of Rheumatology arteritis
Chapter 103, Evaluation of children with Columbia University Irving Medical Center/
rheumatologic complaints New York Presbyterian Hospital Costantino Pitzalis, MD, PhD, FRCP
New York, New York Centre for Experimental Medicine and
Voon H. Ong, PhD, FRCP Chapter 101, Management of rheumatoid arthritis in Rheumatology
Senior Lecturer in Rheumatology patients with prior exposure to conventional synthetic William Harvey Research Institute
Centre for Rheumatology disease-modifying antirheumatic drugs (csDMARDs) Queen Mary University of London
University College London (UCL) London, United Kingdom
Royal Free Hospital Matthew J.S. Parker, MBChB, MRCP, FRACP Chapter 33, Minimally invasive procedures
London, United Kingdom Staff Specialist
Chapter 149, Clinical and serologic features of Department of Rheumatology Denis Poddubnyy, MD, MSc (Epi)
systemic sclerosis Royal Prince Alfred Hospital Professor of Rheumatology
Clinical Lecturer Rheumatology Unit
Philippe Orcel, MD, PhD University of Sydney Department of Gastroenterology, Infectious Diseases
Honorary Professor of Rheumatology Sydney, Australia and Rheumatology
University of Paris Faculty of Medicine Chapter 210, Hemophilia-associated arthritis Charité—Universitätsmedizin Berlin
Former Chief Head of the Spondyloarthritis Liaison Research
Department of Musculoskeletal Diseases Ejaz Pathan, MD, PhD, MRCP Group
Rheumatology and Bone Diseases Consultant Rheumatologist Epidemiology
Hospital Lariboisière, Assistance Publique–Hôpitaux Newcastle upon Tyne Hospitals NHS Foundation German Rheumatism Research Centre
de Paris Trust Berlin, Germany
Paris, France Newcastle upon Tyne, United Kingdom Chapter 125, Management of axial
Chapter 213, Gaucher disease Chapter 116, Reactive arthritis spondyloarthritis
xx CONTRIBUTORS
Janet E. Pope, MD, MPH, FRCPC Soumya Raychaudhuri, MD, PhD Bethan Richards, MBBS, MMed(ClinEpi),
Professor of Medicine Professor of Medicine and Biomedical Informatics M Sports Med, PhD
Medicine Harvard Medical School Head
Division of Rheumatology Associate Physician Department of Rheumatology
University of Western Ontario Divisions of Rheumatology and Genetics Royal Prince Alfred Hospital
Head Brigham and Women’s Hospital Camperdown, New South Wales, Australia
Division of Rheumatology Boston, Massachusetts Deputy Director
St. Joseph’s Health Care Institute Member Institute for Musculoskeletal Health
London, Ontario, Canada Medical and Population Genetics Sydney Local Health District
Chapter 141, Assessing disease activity and outcome Broad Institute Clinical Senior Lecturer
in systemic lupus erythematosus Cambridge, Massachusetts University of Sydney
Visiting Professor Sydney, New South Wales, Australia
Anna Postolova, MD, MPH UK Centre for Genetics and Genomics Versus Arthritis Chapter 51, Treatment recommendations and “treat
Allergy/Immunology/Rheumatology University of Manchester to target”
Menlo Medical Clinic Manchester, United Kingdom
. In ion T
Menlo Park, California Chapter 94, Genetics of rheumatoid arthritis Bruce Richardson, BS, MD, PhD
ed er s IN
Chapter 158, Clinical significance of autoantibodies Huetwell Professor of Medicine
in inflammatory muscle disease Anthony C. Redmond, PhD Medicine
Professor and Head University of Michigan
rv vi is R
Andrew J. Price, MB BChir, BSc, DPhil, FRCS Section of Clinical Biomechanics and Physical Medicine
c. .
Ann Arbor, Michigan
Professor of Orthopaedic Surgery Leeds Institute of Rheumatic and Musculoskeletal Chapter 140, Drug-induced lupus
se se rm P
Nuffield Department of Orthopaedics Medicine
Rheumatology and Musculoskeletal Sciences University of Leeds Pascal Richette, MD, PhD
re El pe R
University of Oxford NIHR Leeds Biomedical Research Centre Professor of Rheumatology
Consultant Orthopaedic Surgeon Leeds Teaching Hospitals NHS Trust Rheumatology
s 3. t FO
Nuffield Orthopaedic Centre Leeds, United Kingdom Hôpital Lariboisière
Oxford, United Kingdom Chapter 84, The ankle and foot Assistance Publique-Hôpitaux de Paris
Chapter 83, The knee Paris, France
Westley H. Reeves, MD
Chapter 212, Hemochromatosis
Katherine P. Pryor, MD, MS Marcia Whitney Schott Professor of Medicine
Clinical Fellow
ig 20 ith OT
Division of Rheumatology, Allergy & Clinical
Immunology
University of Florida College of Medicine
Christopher T. Ritchlin, MD, MPH
Center for Musculoskeletal Research
Gainesville, Florida
N
ht 2 ou University of Rochester Medical Center
Chapter 209, Rheumatoid manifestations of Chapter 138, Autoantibodies in systemic lupus Rochester, New York
endocrine and metabolic diseases and erythematosus Chapter 129, Etiology and pathogenesis of psoriatic
,
treatments
ig se ES
Elaine F. Remmers, PhD arthritis
Luca Quartuccio, MD, PhD Associate Investigator Susan Y. Ritter, MD, PhD
Prof Inflammatory Disease Section Associate Physician
w
National Human Genome Research Institute

yr u G
Department of Medicine Division of Rheumatology, Inflammation and

Rheumatology Clinic National Institutes of Health Immunity
Bethesda, Maryland
op er A
Academic Hospital Santa Maria della

Al ht s

Misericordia Chapter 17, Principles and techniques in molecular
Instructor in Medicine
C th P
University of Udine biology

Udine, Italy Luis Requena, MD Boston, Massachusetts
©
LE
Chapter 171, Cryoglobulinemia Professor of Dermatology Chapter 176, Relapsing polychondritis

Department of Dermatology
Lars Rackwitz, MD Philip C. Robinson, MBChB, PhD
Fundación Jeménez Díaz
Senior Consultant University of Queensland Faculty of Medicine
N MP
Universidad Autónoma
Department of Orthopaedics and Trauma Brisbane, Australia
Madrid, Spain
Surgery Royal Brisbane & Women’s Hospital
lr
Chapter 170, Cutaneous vasculitis and panniculitis

Evangelisches Waldkrankenhaus Spandau Metro North Hospital & Health Service
o
Berlin, Germany Gary Reynolds, BSc, MRCP, PhD

SA
Queensland, Australia
Chapter 15, Principles of tissue engineering and Clinical Lecturer Chapter 180, The epidemiology of coronavirus
o
cell- and gene-based therapy Translational and Clinical Research Institute disease 2019 (COVID-19) and rheumatic
Newcastle University disease
Helga Radner, MD Newcastle Upon Tyne, United Kingdom
Medical University Vienna William H. Robinson, MD, PhD
Chapter 74, Emerging therapeutic targets
Department of Internal Medicine III Professor of Medicine
Division of Rheumatology John A. Reynolds, MRCP, PhD, MBChB. BMedSc Division of Immunology and Rheumatology
Vienna, Austria Clinical Senior Lecturer Stanford School of Medicine
Chapter 42, Multimorbidity Rheumatology Research Group Stanford
Institute of Inflammation and Ageing Palo Alto, California
Aardra Rajendran, MD College of Medical and Dental Sciences Chapter 12, The complement system
Internal Medicine Resident University of Birmingham
Johns Hopkins Hospital Honorary Consultant Rheumatologist
Baltimore, Maryland Valerie J. Rogers, MBBS, MRCPCH, BA (Hons)
Rheumatology Department
Chapter 145, Systemic lupus erythematosus in QTS
Sandwell and West Birmingham NHS Trust
pregnant patients and neonatal lupus Consultant Paediatric Rheumatologist
Birmingham, United Kingdom
Department of Paediatric Rheumatology
Chapter 67, Overview of biologic agents
Sofia Ramiro, MD, PhD Bristol Royal Hospital for Children
Rheumatology Clio Ribbens, MD, PhD Bristol, United Kingdom
Leiden University Medical Center Head of Clinic Consultant in Paediatric and Adolescent Chronic
Leiden, The Netherlands Department of Rheumatology Pain
Rheumatology University Hospital of Liège Bath Centre for Pain Services
Zuyderland Medical Center Liège, Belgium Royal National Hospital For Rheumatic Diseases
Heerlen, The Netherlands Chapter 47, Bone scintigraphy and positron emission Bath, United Kingdom
Chapter 120, Clinical features of axial spondyloarthritis tomography Chapter 217, Hypermobility syndrome
CONTRIBUTORS xxi
Paul L. Romain, MD Jane E. Salmon, MD Hans-Georg Schaible, MD

Corresponding Member of the Faculty of Collette Kean Research Chair Director
Medicine Medicine-Rheumatology University Hospital Jena
Harvard Medical School Hospital for Special Surgery Institute of Physiologie I
Division of Rheumatology and Clinical Professor Jena, Germany
Immunology Department of Medicine Chapter 6, Scientific basis of pain
Beth Israel Deaconess Medical Center Weill Cornell Medical College
Boston, Massachusetts New York, New York Jose U. Scher, MD
Chapter 28, Ethics in clinical trials Chapter 136, Immunopathology of systemic lupus Associate Professor of Medicine
erythematosus Division of Rheumatology
Ivan O. Rosas, MD NYU Grossman School of Medicine
Professor of Medicine Isidro B. Salusky, MD Director
Baylor College of Medicine Distinguished Professor of Pediatrics Psoriatic Arthritis Center
Pulmonary, Critical Care and Sleep Section David Geffen School of Medicine at UCLA NYU Langone Health
Houston, Texas Los Angeles, California Director
. In ion T
Chapter 37, The lungs in rheumatic disease Chapter 204, Osteomalacia, rickets, and renal Microbiome Center for Rheumatology and
Autoimmunity (MiCRA)
ed er s IN
osteodystrophy
Ann K. Rosenthal, MD NYU Grossman School of Medicine
Associate Chief of Staff for Research and Carlo Salvarani, MD New York, New York
rv vi is R
c. .
Chapter 22, The microbiome in rheumatic diseases
Development Professor of Rheumatology
se se rm P
Clement J. Zablocki VA Medical Center Rheumatology Georg Schett, MD
Will and Cava Ross Professor of Medicine Azienda USL-IRCCS di Reggio Emilia and Professor of Rheumatology and Immunology
Chief of Rheumatology UNIMORE
re El pe R
Department of Internal Medicine 3
Associate Dean of Research Reggio Emilia, Italy Friedrich Alexander University (FAU)
Medical College of Wisconsin Chapter 166, Polymyalgia rheumatica and giant cell
s 3. t FO
Erlangen, Germany
Milwaukee, Wisconsin arteritis
Chapter 13, Osteoimmunology
Chapter 196, Calcium pyrophosphate deposition
disease (pseudogout) Linda J. Sandell, PhD Adam I. Schiffenbauer, MD
Professor Staff Clinician
Elka Rubin
ig 20 ith OT
Medical Student
University of Arizona
Orthopaedic Surgery
Washington University
St. Louis, Missouri
Environmental Autoimmunity Group
National Institute of Environmental Health Sciences
N
Tucson, Arizona ht 2 ou Chapter 2, The articular cartilage Bethesda, Maryland
Chapter 44, Magnetic resonance imaging Chapter 159, Management of inflammatory muscle
Vaneet K. Sandhu, MD disease
,
ig se ES
Martin Rudwaleit, MD Associate Professor

Professor of Rheumatology Rheumatology Alan L. Schiller, MD
Department of Internal Medicine and Loma Linda University Founding Chair of Pathology
Loma Linda, California Nova Southeastern University Medical School
w
Rheumatology
yr u G
Klinikum Bielefeld Assistant Professor Director

University of Bielefeld Medicine Pathology Residency Program
op er A
Al ht s
Bielefeld, Germany University of California, Riverside Miami, Florida

Riverside, California Irene Heinz Given and John Laporte Given
C th P

spondyloarthritis Chapter 134, Clinical features of systemic lupus Professorship of Pathology and Chair Emeritus
©
erythematosus Icahn School of Medicine

LE
The Mount Sinai Medical Center NYC

Bram A. Rutgers, MD, PhD
Maria Sandovici, MD, PhD New York, New York
Department of Rheumatology and Clinical Chapter 218, Bone tumors
Immunology
N MP
University Medical Center Groningen Immunology

University Medical Center Groningen
Naomi Schlesinger, MD
University of Groningen
lr
Groningen, The Netherlands University of Groningen
Chief
o
Chapter 162, Biology and immunopathogenesis of Groningen, The Netherlands

SA
vasculitis Chapter 162, Biology and immunopathogenesis of
Rutgers—Robert Wood Johnson Medical School
vasculitis
o
New Brunswick, New Jersey

Marite Rygg, MD, PhD Chapter 194, Clinical features of gout
Professor Anne-Lene Sand-Svartrud
Department of Clinical and Molecular National Advisory Unit on Rehabilitation in Benjamin E. Schreiber, MBBS, MA, MRCP
Medicine Rheumatology Consultant in Pulmonary Hypertension and
NTNU—Norwegian University of Science and Division of Rheumatology and Research Rheumatology
Technology Diakonhjemmet Hospital Rheumatology
Consultant Oslo, Norway Royal Free Hospital
Department of Pediatrics Chapter 102, Multidisciplinary Honorary Senior Lecturer
St. Olavs Hospital University Hospital of nonpharmacologic approach to rheumatoid Department of Medicine
Trondheim arthritis University College London
Trondheim, Norway London, United Kingdom
Chapter 105, Clinical features of juvenile idiopathic Carla R. Scanzello, MD, PhD Chapter 36, The cardiovascular system in rheumatic
arthritis Section Chief disease
Rheumatology
Kenneth G. Saag, MD, MSc Corporal Michael J. Crescenz VA Medical Daniella M. Schwartz, MD
Anna Waters Professor and Director Center Assistant Clinical Investigator
Division of Clinical Immunology and Associate Professor of Medicine Food Allergy Research Unit
Rheumatology Rheumatology Laboratory of Allergic Diseases
Department of Medicine University of Pennsylvania Perelman School of National Institute of Allergy and Infectious Diseases
University of Alabama at Birmingham Medicine National Institutes of Health
Birmingham, Alabama Philadelphia, Pennsylvania Bethesda, Maryland
Chapter 62, Systemic glucocorticoids in Chapter 185, Pathogenesis and pathology of Chapter 9, Signal transduction in immune cells
rheumatology osteoarthritis Chapter 10, Cytokines
xxii CONTRIBUTORS
Aziz Shaibani, MD Professor of Medicine Jeffrey A. Sparks, MD, MMSc
Director Dartmouth Geisel School of Medicine Assistant Professor of Medicine
Nerve and Muscle Center of Texas Hanover, New Hampshire Department of Medicine
Houston Neurocare Chapter 155, Localized scleroderma and Division of Rheumatology, Inflammation, and
Clinical Professor of Medicine scleroderma-like syndromes Immunity
Baylor College of Medicine Brigham and Women’s Hospital
Houston, Texas Nora G. Singer, MD Boston, Massachusetts
Chapter 55, Placebo, nocebo, caring, and healing in Professor of Medicine and Pediatrics Chapter 42, Multimorbidity
rheumatology Case Western Reserve University School of Chapter 175, Sarcoidosis
Medicine
Leena Sharma, MD Director John Stack, MD
Chang-Lee Professor of Preventive Rheumatology Division of Rheumatology Mater Misericordiae University Hospital
Professor of Medicine and Preventive Medicine The Metro School of Medicine, University College Dublin
Northwestern University Feinberg School of Health System Dublin, Ireland
Medicine Cleveland, Ohio Chapter 197, Basic calcium phosphate crystal
. In ion T
Chicago, Illinois Chapter 103, Evaluation of children with deposition disease
Chapter 182, Local and systemic risk factors for rheumatologic complaints
ed er s IN
incidence and progression of osteoarthritis David Stanley, MB, BS, BSc (Hons), FRCS
Emily Sirotich, BSc Consultant Orthopaedic Surgeon
Robert H. Shmerling, MD
rv vi is R
Parkhead Consultancy
c. .
Department of Health Research Methods, Evidence,
Corresponding Member of the Faculty of Medicine and Impact Sheffield, United Kingdom
se se rm P
Harvard Medical School McMaster University Chapter 80, The elbow
Division of Rheumatology and Clinical Immunology Hamilton, Ontario, Canada
Beth Israel Deaconess Medical Center Virginia D. Steen, MD
re El pe R
Canadian Arthritis Patient Alliance Professor of Medicine
Boston, Massachusetts Toronto, Ontario, Canada Medstar Georgetown University Hospital
s 3. t FO
Chapter 28, Ethics in clinical trials Chapter 180, The epidemiology of coronavirus
Rheumatology Division
disease 2019 (COVID-19) and rheumatic disease
Bernadette C. Siaton, MD Washington, DC
Assistant Professor of Medicine Chapter 152, Management of systemic sclerosis
Judith A. Smith, MD, PhD
Division of Rheumatology and Clinical Associate Professor of Pediatrics Allen C. Steere, MD
Immunology
ig 20 ith OT
University of Maryland School of Medicine
Baltimore, Maryland
Division of Allergy Immunology and
Rheumatology
University of Wisconsin School of Medicine and
Director
N
Chapter 86, Entrapment neuropathies and Public Health Translational Research in Rheumatology
ht 2 ou
compartment syndromes Madison, Wisconsin Massachusetts General Hospital
Chapter 108, The juvenile-onset
,
Richard M. Siegel, MD, PhD Boston, Massachusetts

ig se ES
spondyloarthropathies Chapter 114, Lyme and other tickborne diseases

Global Head, Translational Medicine
Autoimmunity, Transplantation and Inflammation
Stacy E. Smith, MD Coen A. Stegeman, MD, PhD
Novartis Institutes for BioMedical Research
Chief and Distinguished Barbara N. Weissman Professor
w
yr u G
Basel, Switzerland
Chair Department of Nephrology
Chapter 10, Cytokines
Division of Musculoskeletal Imaging and University Medical Center Groningen
op er A
Al ht s
Daniela Sieghart, PhD Intervention University of Groningen

Department of Radiology Groningen, The Netherlands
C th P
Junior Scientist
Medical University of Vienna Medical Director Chapter 162, Biology and immunopathogenesis of
©
Vienna, Austria Orthopaedic and Arthritis Center vasculitis

LE
Chapter 96, Autoantibodies in rheumatoid arthritis

Clinical Director
Quantitative Musculoskeletal Imaging Günter Steiner, PhD Prof
Group Director of the Ludwig Boltzmann Institute for
Stuart L. Silverman, MD
N MP
Imaging Director Arthritis and Rehabilitation

Clinical Professor of Medicine
STRATUS Center for Simulation in Medical Medical University of Vienna
Cedars-Sinai Medical Center
lr
Education Department of Medicine III

Clinical Professor of Medicine
Brigham and Women’s Hospital Division of Rheumatology
o
UCLA David Geffen School of Medicine

SA
Harvard Medical School Vienna, Austria

Boston, Massachusetts Chapter 96, Autoantibodies in rheumatoid arthritis
o
Chapter 199, Clinical evaluation and clinical features

Chapter 43, Conventional radiography and
of osteoporosis Andre F. Steinert, MD
computed tomography
Professor and Head
Julia F. Simard, ScD Department of Orthopaedics, Arthroplasty, Trauma
Associate Professor Josef S. Smolen, MD
and Shoulder Surgery
Departments of Epidemiology & Population Health, Emeritus Professor
Rhön-Klinikum Campus Bad Neustadt
and Medicine (Immunology and Rheumatology) Division of Rheumatology
Bad Neustadt, Germany
Stanford University School of Medicine Department of Medicine 3
Chapter 15, Principles of tissue engineering and
Stanford, California Medical University of Vienna
cell- and gene-based therapy
Chapter 23, Principles of epidemiology Vienna, Austria
Chapter 99, Assessment of the patient with George Stojan, MD
Barry P. Simmons, MD rheumatoid arthritis and the measurement of Global SLE Medical Affairs Director at UCB
Associate Professor of Orthopaedic Surgery outcomes Baltimore, Maryland
Harvard Medical School Chapter 160, Metabolic, drug-induced, and other
Chief Emeritus Daniel H. Solomon, MD, MPH noninflammatory myopathies
Hand and Upper Extremity Service Professor
Brigham and Women’s Hospital Division of Rheumatology Vibeke Strand, MD, MACR, FACP
Boston, Massachusetts Brigham and Women’s Hospital Adjunct Clinical Professor
Chapter 81, The wrist and hand Professor Division of Immunology/Rheumatology
Medicine Stanford University
Robert W. Simms, MD Harvard Medical School Palo Alto California
Emeritus Professor of Medicine Boston, Massachusetts Chapter 141, Assessing disease activity and outcome
Boston University School of Medicine Chapter 42, Multimorbidity in systemic lupus erythematosus
CONTRIBUTORS xxiii
Paul Sufka, MD Louise M. Topping, BSc, PhD Désirée van der Heijde, MD, PhD
Rheumatologist Kennedy Institute of Rheumatology Professor of Rheumatology
Rheumatology University of Oxford Rheumatology
HealthPartners Oxford, United Kingdom Leiden University Medical Center
St. Paul, Minnesota Chapter 95, Animal models of rheumatoid arthritis Leiden, The Netherlands
Chapter 180, The epidemiology of coronavirus Chapter 49, Use of imaging as an outcome measure
disease 2019 (COVID-19) and rheumatic disease Michael Toprover, MD in clinical trials
Assistant Professor of Medicine
James K. Sullivan, BA Division of Rheumatology Floris A. van Gaalen, MD, PhD
Medical Student Department of Medicine Associate Professor
Cleveland Clinic Lerner College of Medicine of NYU Grossman School of Medicine Department of Rheumatology
Case Western Reserve University New York, New York Leiden University Medical Center
Cleveland Ohio Chapter 11, Inflammation and its chemical mediators Leiden, The Netherlands
Chapter 58, Indications for and long-term Chapter 119, Inflammatory back pain
complications of total hip and knee arthroplasty Karina Torralba, MD, MACM
. In ion T
Chief Margot Van Mechelen, MD, PhD, Dr
Pawel Szulc, MD, PhD Division of Rheumatology
ed er s IN
Rheumatology
University of Lyon Department of Medicine University Hospitals Leuven/Skeletal Biology and
Lyon, France Loma Linda University Engineering Center KU Leuven
rv vi is R
Chapter 201, Biochemical markers of bone turnover
c. .
Loma Linda, California Leuven, Belgium
in postmenopausal osteoporosis Chapter 134, Clinical features of systemic lupus Chapter 123, Animal models of spondyloarthritis
se se rm P
erythematosus
Chen Tang, MD Ronald F. van Vollenhoven, MD, PhD
Division of Rheumatology Zahi Touma, MD, PhD
re El pe R
Professor and Chair
Cedars-Sinai Medical Center Associate Professor of Medicine Rheumatology and Clinical Immunology
s 3. t FO
University of Toronto Amsterdam University Medical Centers
Chapter 93, Imaging of rheumatoid arthritis Department of Medicine Director
Toronto Western Hospital Amsterdam Rheumatology Center
Shiyu Tang, PhD Toronto, Ontario, Canada Amsterdam, The Netherlands
Postdoctoral Fellow Chapter 24, Principles of clinical outcome assessment
Medicine ig 20 ith OT
Department of Diagnostic Radiology & Nuclear

Adriana H. Tremoulet, MD, MAS
Associate Director
Chapter 66, Kinase inhibitors and other synthetic
agents
Claire Y.J. Vandevelde, MD, MRCP

Baltimore, Maryland
N
ht 2 ou Kawasaki Disease Research Center Consultant Rheumatologist
Chapter 45, Functional magnetic resonance University of California San Diego School of Leeds Teaching Hospitals NHS Trust
imaging Medicine Leeds, United Kingdom
,
La Jolla, California
ig se ES
Peter C. Taylor, MA, PhD, FRCP Chapter 187, Imaging of osteoarthritis

Director
Professor of Rheumatology Kawasaki Disease Clinic
Nuffield Department of Orthopaedics,
John Varga, MD
Rady Children’s Hospital-San Diego Frederick G L Huetwell Professor of Internal
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Rheumatology and Musculoskeletal Sciences San Diego, California Medicine

University of Oxford Chapter 168, Kawasaki disease Chief
op er A
Botnar Research Centre

Al ht s
Headington, Oxford, United Kingdom Leendert Trouw, PhD
C th P

Chapter 70, Tumor necrosis factor inhibitors Associate Professor and Group Leader University of Michigan
Leiden University Medical Center
©
Robert Terkeltaub, MD Ann Arbor, Michigan

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Leiden, The Netherlands Chapter 150, Etiology and pathogenesis of systemic

Chief Chapter 96, Autoantibodies in rheumatoid arthritis
Rheumatology Section sclerosis
Medicine Rocky S. Tuan, PhD
N MP
VA Healthcare System Dimitrios Vassilopoulos, MD

Vice-Chancellor and President
Professor of Medicine Professor of Medicine (Rheumatology)
The Chinese University of Hong Kong
lr
Division of Rheumatology, Allergy, and Immunology National and Kapodistrian University of Athens
Institute for Tissue Engineering and Regenerative
School of Medicine
o
University of California, San Diego

SA
Medicine
San Diego, California Chair, 2nd Department of Medicine and
Hong Kong SAR, China
Laboratory
o
Chapter 195, Management of gout and Chapter 15, Principles of tissue engineering and
hyperuricemia Hippokration General Hospital
cell- and gene-based therapy
Athens, Greece
Afton R. Thomas, DO Ilker Uçkay, MD, Prof. Dr. med. Chapter 113, Viral infections
Assistant Professor of Medicine Infectiology
Division of Rheumatology and Clinical Balgrist University Hospital Douglas J. Veale, MD, FRCPI, FRCP(Lon)
Immunology Zurich, Switzerland Director of Translational Research
University of Maryland School of Medicine Chapter 111, Bacterial native joint arthritis
The Centre for Arthritis and Rheumatic Disease
Baltimore, Maryland St. Vincent’s University Hospital
Chapter 86, Entrapment neuropathies and Hisanori Umehara, MD, PhD Professor of Medicine
compartment syndromes Director of Rheumatology and Immunology University College Dublin
Nagahama City Hospital Fellow
Jennifer E. Thorne, MD, PhD Shiga, Japan Conway Institute of Biomolecular and Biomedical
Cross Family Professor Chapter 178, IgG4-related disease Medicine
Ophthalmology Dublin, Ireland
Johns Hopkins University School of Medicine Kornelis S.M. van der Geest, MD, PhD Chapter 131, Management of psoriatic arthritis
Professor Department of Rheumatology and Clinical
Epidemiology Immunology Gwenny M. Verstappen, PharmD, PhD
Johns Hopkins University Bloomberg School of University Medical Center Groningen Rheumatology and Clinical Immunology
Public Health University of Groningen University of Groningen
Baltimore, Maryland Groningen, The Netherlands University Medical Center Groningen
Chapter 35, Ocular manifestations of rheumatic Chapter 162, Biology and immunopathogenesis of Groningen, The Netherlands
diseases vasculitis Chapter 146, Sjögren syndrome
xxiv CONTRIBUTORS
Sebastien Viatte, MD, PhD Abdulla Watad, MD Departments of Medical & Molecular Genetics and
Lecturer in Genetics Doctor Medicine/Nephrology
Centre for Genetics and Genomics Versus Internal Medicine B IU-Simon Cancer Center
Arthritis and Lydia Becker Institute of Sheba Medical Centre Indiana University School of Medicine
Immunology Tel Aviv, Israel Indianapolis, Indiana
Centre for Musculoskeletal Research Senior Lecturer Chapter 3, Bone structure and function
The University of Manchester Division of Rheumatology
Manchester, United Kingdom Sheba Medical Center David J. Wilkinson, BSc, MRes, PhD
Chapter 94, Genetics of rheumatoid arthritis Tel Aviv University Department of Musculoskeletal Biology and Ageing
Tel-Hashomer, Israel Sciences
Tonia L. Vincent, MBBS, PhD, FRCP Chapter 118, Enthesopathies Institute of Life Course and Medical Sciences
Professor of Musculoskeletal Biology University of Liverpool
Nuffield Department of Orthopaedics, Richard A. Watts, MA, DM, FRCP Liverpool, United Kingdom
Rheumatology & Musculoskeletal Sciences Honorary Professor Chapter 14, Joint tissue destruction and proteolysis
Kennedy Institute of Rheumatology Norwich Medical School
. In ion T
Honorary Consultant Rheumatologist University of East Anglia David E. Williams, BEng, PhD Dr.
Norwich, United Kingdom School of Engineering
ed er s IN
Oxford University Hospitals Trust
Oxford, United Kingdom Chapter 161, Classification and epidemiology of Cardiff University
Chapter 184, Animal models of osteoarthritis vasculitis Cardiff, Wales
rv vi is R
Chapter 5, Biomechanics of peripheral joints and spine
c. .
Edward M. Vital, PhD, MRCP(UK) Michael E. Weinblatt, MD
Richard Williams, BSc, MSc, PhD
se se rm P
Associate Professor John R. and Eileen K. Riedman Professor of
Medicine Professor of Immunology
Honorary Consultant and NIHR Clinician
Kennedy Institute of Rheumatology
re El pe R
Scientist Harvard Medical School
Division of Rheumatology, Inflammation and University of Oxford
Leeds Institute of Rheumatic and Musculoskeletal
s 3. t FO
Medicine Immunity
Brigham and Women’s Hospital Chapter 95, Animal models of rheumatoid arthritis
University of Leeds
Leeds Biomedical Research Centre Boston, Massachusetts
Hannah Wilson, BM BCh, MA(Oxon), MRCS
Leeds Teaching Hospitals NHS Trust Chapter 63, Methotrexate
Research Fellow
ig 20 ith OT
Leeds, United Kingdom
Chapter 73, Inhibitors of B cells
Isabell S. von Loga, AB, MBBS

Matthew R. Weir, MD
Professor and Director
Division of Nephrology
Nuffield Department of Orthopaedics
Rheumatology and Musculoskeletal Sciences
N
Alumni ht 2 ou Medicine
University of Maryland School of Medicine, Chapter 83, The knee
Nuffield Department of Orthopaedics,
Rheumatology & Musculoskeletal Baltimore, Maryland
Kevin L. Winthrop, MD, MPH
,
Chapter 39, The kidneys in rheumatic diseases

ig se ES
Sciences Professor of Infectious Diseases and Public Health

Kennedy Institute of Rheumatology Department of Medicine
Michael H. Weisman, MD
University of Oxford OHSU-PSU School of Public Health
Adjunct Professor of Medicine
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Division of Immunology and Rheumatology Oregon Health & Science University

Chapter 184, Animal models of osteoarthritis Portland, Oregon
Stanford University
op er A
Chapter 76, Infections in rheumatoid arthritis:

Al ht s
Dawn M. Wahezi, MD Professor of Medicine, Emeritus

Division of Rheumatology biologic therapy and JAK inhibitors
C th P
Chief
Division of Pediatric Rheumatology Claudia M. Witt, MD, MBA
Distinguished Professor of Medicine, Emeritus
©
Director Professor and Chair

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Pediatric Rheumatology Fellowship Program David Geffen School of Medicine at University of

Institute for Complementary and Integrative
Associate Professor California, Los Angeles
Medicine
Albert Einstein College of Medicine Los Angeles, California
University Hospital Zurich and University Zurich
N MP
Chapter 134, Clinical features of systemic lupus

Bronx, New York Zurich, Switzerland
erythematosus
Chapter 109, Systemic autoimmune rheumatic Professor of Medicine
lr
diseases in children Pamela F. Weiss, MD, MSCE Center for Integrative Medicine
o

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Associate Professor of Pediatrics

Daniel J. Wallace, MD Perelman School of Medicine Baltimore, Maryland
Rheumatology Chapter 56, Complementary and alternative medicine
o
University of Pennsylvania
Attending Physician
Division of Rheumatology Gerhard Witzmann, MD
Chapter 134, Clinical features of systemic lupus Department of Rheumatology
Children’s Hospital of Philadelphia
erythematosus Hietzing Hospital
Philadelphia, Pennsylvania
Chapter 108, The juvenile-onset Vienna, Austria
Zachary S. Wallace, MD, MSc Appendix: Classification and diagnostic criteria
spondyloarthropathies
Clinical Epidemiology Program and
Rheumatology Unit Harriet Branford White, MB ChB, DPhil, FRCS John B. Wong, MD
Division of Rheumatology, Allergy, and (Tr & Orth) Professor of Medicine
Immunology Trauma and Orthopaedic Registrar Tufts University School of Medicine
Massachusetts General Hospital North West Thames Rotation Vice Chair of Academic Affairs
Harvard Medical School St Mary’s Hospital Chief Division of Clinical Decision Making
Boston, Massachusetts Imperial NHS Trust Department of Medicine
Chapter 180, The epidemiology of coronavirus London, United Kingdom Tufts Medical Center
disease 2019 (COVID-19) and rheumatic Chapter 218, Bone tumors Boston, Massachusetts
disease Chapter 25, Principles of health economics
Kenneth E. White, PhD
Gary Warburton, DDS, MD, FDSRCS, FACS David D. Weaver Professor of Genetics Anthony D. Woolf, BSc, MBBS, FRCP
Professor of Oral & Maxillofacial Surgery IUPUI Chancellor’s Professor Professor
Oral & Maxillofacial Surgery Director Bone and Joint Research Group
University of Maryland School of Dentistry Division of Molecular Genetics and Gene Royal Cornwall Hospitals Trust
Baltimore, Maryland Therapy Truro, Cornwall, United Kingdom
Chapter 85, The temporomandibular joint Vice-Chair for Research Chapter 29, History and physical examination
CONTRIBUTORS xxv
B. Paul Wordsworth, MA, MB, BS, FRCP Jinoos Yazdany, MD, MPH Md Yuzaiful Md Yusof, PhD, MRCP(UK)
Emeritus Professor of Clinical Rheumatology Professor of Medicine NIHR Academic Clinical Lecturer and LTHT
Nuffield Department of Orthopaedics, University of California, San Francisco Consultant Rheumatologist
Rheumatology and Musculoskeletal Sciences San Francisco, California Leeds Institute of Rheumatic and Musculoskeletal
University of Oxford Chapter 180, The epidemiology of coronavirus Medicine
Oxford, United Kingdom disease 2019 (COVID-19) and rheumatic disease University of Leeds
Honorary Consultant Rheumatologist Leeds Biomedical Research Centre
Department of Rheumatology David A. Young, PhD Leeds Teaching Hospitals NHS Trust
Nuffield Orthopaedic Centre Professor Leeds, United Kingdom
Headington, United Kingdom Skeletal Research Group Chapter 73, Inhibitors of B cells
Chapter 216, Heritable connective tissue Newcastle University
disorders Newcastle upon Tyne, United Kingdom
Chapter 14, Joint tissue destruction and proteolysis
Haoyang Zhuang, PhD
Huji Xu, MD, PhD Stephen P. Young, BSc(Hons), PhD Division of Rheumatology, Allergy, & Clinical
. In ion T
Department of Rheumatology and Immunology Reader in Experimental Rheumatology Immunology
Shanghai Changzheng Hospital Institute of Inflammation and Ageing University of Florida College of Medicine
ed er s IN
Second Military Medical University University of Birmingham Gainesville, Florida
Shanghai, China Birmingham, United Kingdom Chapter 138, Autoantibodies in systemic lupus
rv vi is R
Chapter 122, Genetics of axial spondyloarthritis Chapter 19, Metabolomics erythematosus
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se se rm P
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Contents
Volume One SECTION 2
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Clinical Basis of Rheumatic Disease
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SECTION 1 23. Principles of epidemiology
Julia F. Simard and Elizabeth V. Arkema
193
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Scientific Basis of Rheumatic Disease 24. Principles of clinical outcome assessment 198
se se rm P
Sindhu R. Johnson and Zahi Touma
A. Anatomy and Physiology 25. Principles of health economics 203
re El pe R
John B. Wong
1. The synovium 1
Andrew Filer and Christopher D. Buckley 26. Principles of genetic epidemiology 209
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Gisela Orozco and Stephen Eyre
2. The articular cartilage 8
Linda J. Sandell and Brian Johnstone 27. Interpreting the medical literature for the rheumatologist 215
Robert B.M. Landewé
3. Bone structure and function 18
David B. Burr, Teresita Bellido, and Kenneth E. White
28. Ethics in clinical trials 222
4.
5.
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Tendons and ligaments
Stephanie G. Dakin and Andrew J. Carr
Biomechanics of peripheral joints and spine

31
38
Paul L. Romain and Robert H. Shmerling
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David E. Williams and Cathy Holt
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6. Scientific basis of pain 49 SECTION 3
,
Hans-Georg Schaible
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Approach to the Patient

B. Immunology and Inflammation
7. Principles of innate immunity 55 29. History and physical examination 225
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Anthony D. Woolf
Tsuneyasu Kaisho and Shizuo Akira
8. Principles of adaptive immunity 62 30. Laboratory tests in rheumatic disorders 241

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Sergei P. Atamas and Martin F. Flajnik Eugen Feist and Gerd-Rüdiger Burmester
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9. Signal transduction in immune cells 72 31. Aspiration and injection of joints and periarticular tissue
Eric P. Hanson, Daniella M. Schwartz, Michael Bonelli, John J. O’Shea, and Martin Aringer and intralesional therapy 247
©
Esperanza Naredo and Ingrid Möller

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10. Cytokines 80
John J. O’Shea, Massimo Gadina, Daniella M. Schwartz, Richard M. Siegel, and Joshua Farber 32. Synovial fluid analysis 260
Klaus P. Machold
11. Inflammation and its chemical mediators 96
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Ruth Fernandez-Ruiz, Michael Toprover, and Michael H. Pillinger 33. Minimally invasive procedures 265
Alessandra Nerviani, Frances Humby, and Costantino Pitzalis
12. The complement system 109
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William H. Robinson 34. The skin in rheumatic disease 271

o
Markus Böhm, Thomas A. Luger, and Jan Ehrchen

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13. Osteoimmunology 115

Georg Schett and Aline Bozec 35. Ocular manifestations of rheumatic diseases 281
o
Renuka Mopuru, Benjamin C. Chaon, Jennifer E. Thorne, and Douglas A. Jabs

14. Joint tissue destruction and proteolysis 120
David J. Wilkinson and David A. Young
36. The cardiovascular system in rheumatic disease 290
15. Principles of tissue engineering and cell- and gene-based Disha Midha, Benjamin E. Schreiber, David P. D’Cruz, and John (Gerry) Coghlan
therapy 130 37. The lungs in rheumatic disease 299

Lars Rackwitz, Ulrich Nöth, Andre F. Steinert, and Rocky S. Tuan Tracy J. Doyle, Ivan O. Rosas, and Paul F. Dellaripa
38. The gastrointestinal tract in rheumatic disease 305

C. Systems Biology Natasha Kamal and Raymond K. Cross
16. Big Data analysis 137 39. The kidneys in rheumatic diseases 312
Paul Martin, Kimme Hyrich, and Nophar Geifman
Jay I. Lakkis and Matthew R. Weir
17. Principles and techniques in molecular biology 145
Elaine F. Remmers and Michael J. Ombrello
40. The nervous system in rheumatic disease 326
Shamik Bhattacharyya
18. Proteomics 158
Joshua LaBaer and Timothy L. Karr 41. The muscles in rheumatic disease 333
Sarfaraz A. Hasni and Randall E. Keyser
19. Metabolomics 165
Stephen P. Young 42. Multimorbidity 340
Helga Radner, Jeffrey A. Sparks, and Daniel H. Solomon
20. Epigenetics 171
Caroline Ospelt and Steffen Gay
21. Precision medicine and pharmacogenomics in rheumatology 178

Mary Abraham, Jeffrey D. Greenberg, and Bruce N. Cronstein
22. The microbiome in rheumatic diseases 183

Julia Manasson, Steven B. Abramson, and Jose U. Scher
xxxi
xxxii Contents
SECTION 4
66. Kinase inhibitors and other synthetic agents 527
Ronald F. van Vollenhoven
Evaluation of the Patient: Imaging Techniques C. Biologic Agents

67. Overview of biologic agents 535
43. Conventional radiography and computed tomography 345 Benjamin A. Fisher, John A. Reynolds, Roy Jefferis, and Caroline Gordon
Stacy E. Smith and Lawrence Lo
68. Interleukin-1 inhibitors 541
44. Magnetic resonance imaging 358 Cem Gabay
Elka Rubin and Garry E. Gold
69. Interleukin-6 inhibitors 548
45. Functional magnetic resonance imaging 367 Berber de Boer and Thomas W.J. Huizinga
Shiyu Tang and Rao P. Gullapalli
70. Tumor necrosis factor inhibitors 556
46. Musculoskeletal ultrasonography 373 Peter C. Taylor and Maha A. Azeez
David Kane
71. Interleukin-17, interleukin-12, and interleukin-23 inhibitors 578
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47. Bone scintigraphy and positron emission tomography 383 Ruba Kado and David A. Fox
Clio Ribbens and Gauthier Namur
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72. Inhibitors of T-cell costimulation 583
48. Dual x-ray absorptiometry and measurement of bone 393 Ernest H.S. Choy
Mohammed Almohaya, Mohammed Almehthel, and David Kendler
73. Inhibitors of B cells 587
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c. .
49. Use of imaging as an outcome measure in clinical trials 402 Md Yuzaiful Md Yusof, Edward M. Vital, and Paul Emery
Désirée van der Heijde and Robert B.M. Landewé
se se rm P
74. Emerging therapeutic targets 596
John D. Isaacs and Gary Reynolds
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75. Biosimilars in rheumatology 604
SECTION 5
Jonathan Kay
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76. Infections in rheumatoid arthritis: biologic therapy
and JAK inhibitors 617
Principles of Management Kevin L. Winthrop
A. General
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50. The patient perspective
Maarten de Wit
411
SECTION 6
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51. Treatment recommendations and “treat to target” 415
ht 2 ou
Lyn M. March and Bethan Richards
Regional and Widespread Pain
,
52. Arthritis patient education, self-management, and health

ig se ES
promotion 424 77. Neck pain 627

Pamela Donlan and Maura D. Iversen Leslie Barnsley
53. Principles of rehabilitation: physical and occupational therapy 430 78. Low back pain 638
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Rana S. Hinman, Philippa J.A. Nicolson, and Kim L. Bennell Andrew A. Joyce and Zacharia Isaac
54. Multidisciplinary approaches to managing chronic pain in arthritis 438 79. The shoulder 656
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Alice Elizabeth Berry and Sarah Bennett George L.D. Cox

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55. Placebo, nocebo, caring, and healing in rheumatology 443 80. The elbow 671
Elisa Frisaldi, Aziz Shaibani, and Fabrizio Benedetti David Stanley and Amjid Ashraf Ali
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56. Complementary and alternative medicine 447 81. The wrist and hand 676
Brian Berman, Claudia M. Witt, and Chris D’Adamo George S.M. Dyer and Barry P. Simmons
57. Outcomes and perioperative management of patients 82. The hip 684
N MP
Matthew L. Brown and William D. Bugbee

with inflammatory arthritis and systemic lupus erythematosus
undergoing total joint arthroplasty 455 83. The knee 693
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Susan M. Goodman and C. Ronald MacKenzie Hannah Wilson, Rob Middleton, and Andrew J. Price
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58. Indications for and long-term complications of total hip 84. The ankle and foot 707
and knee arthroplasty 462 Anthony C. Redmond
o
James K. Sullivan and Jeffrey N. Katz

85. The temporomandibular joint 718
59. Medication management during preconception, pregnancy, Gary Warburton, Sharon Gordon, and Max R. Emmerling
and lactation 467 86. Entrapment neuropathies and compartment syndromes 721
Bonnie L. Bermas and Monika Østensen
Afton R. Thomas and Bernadette C. Siaton
B. Small Molecules 87. Complex regional pain syndrome

Christopher Chang, Patrick J. McDonnell, and M. Eric Gershwin
732
60. Principles of pharmacologic pain management 475
Robert A. Lavin and Timothy J. Atkinson 88. Fibromyalgia and related syndromes 740
Deeba Minhas and Daniel J. Clauw
61. Nonsteroidal antiinflammatory drugs 482
Carlo Patrono
62. Systemic glucocorticoids in rheumatology 490
SECTION 7
Kenneth G. Saag and Frank Buttgereit
63. Methotrexate 501

Alisa A. Mueller and Michael E. Weinblatt
Rheumatoid Arthritis
64. Synthetic disease-modifying antirheumatic drugs and leflunomide 509
Vivian P. Bykerk and Boulos Haraoui
89. Classification and epidemiology of rheumatoid arthritis 749
Katherine P. Liao
65. Immunosuppressive agents: cyclosporine, cyclophosphamide,
azathioprine, mycophenolate mofetil, and tacrolimus 518 90. Clinical features of rheumatoid arthritis 756
Kavitta B. Allem and Richard M. Keating Richard D. Brasington, Jr. and Jonathan J. Miner
Contents xxxiii
91. Extraarticular features of rheumatoid arthritis 763 112. Mycobacterial, brucellar, fungal, and parasitic arthritis 967
Elena Myasoedova and Eric L. Matteson Javier Márquez and Luis R. Espinoza
92. Common comorbidities in rheumatoid arthritis 771 113. Viral infections 982
Jeffrey R. Curtis and Michael D. George Dimitrios Vassilopoulos and Leonard H. Calabrese
93. Imaging of rheumatoid arthritis 778

Chen Tang, Lindsy Forbess, and Ami Ben-Artzi B. Other Infection-Related Disease
94. Genetics of rheumatoid arthritis 789 114. Lyme and other tickborne diseases 989
Sebastien Viatte and Soumya Raychaudhuri Allen C. Steere
95. Animal models of rheumatoid arthritis 799 115. Acute rheumatic fever 996
Richard Williams and Louise M. Topping Carlos Eduardo de Barros Branco and Luiza Guilherme Guglielmi
96. Autoantibodies in rheumatoid arthritis 805 116. Reactive arthritis 1007

Daniela Sieghart, Leendert Trouw, and Günter Steiner Ejaz Pathan, Ahmed Omar, and Robert D. Inman
97. Pathogenesis and pathology of rheumatoid arthritis 815
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Ellen M. Gravallese and Anna Helena Jonsson
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SECTION 10
98. Preclinical rheumatoid arthritis 835
Parisa Mortaji and Kevin D. Deane
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99. Assessment of the patient with rheumatoid arthritis and the
measurement of outcomes 841 Spondyloarthritis and Psoriatic Arthritis
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Daniel Aletaha and Josef S. Smolen
117. Classification and epidemiology of spondyloarthritis 1023
100. Management of rheumatoid arthritis in csDMARD-naïve patients 852 Martin Rudwaleit
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Andrew R. Melville and Maya H. Buch
118. Enthesopathies 1027
101. Management of rheumatoid arthritis in patients with prior
s 3. t FO
Dennis McGonagle and Abdulla Watad
exposure to conventional synthetic disease-modifying
antirheumatic drugs (csDMARDs) 860 119. Inflammatory back pain 1036
Floris A. van Gaalen
Elizabeth Park and Joan M. Bathon
102. Multidisciplinary nonpharmacologic approach to rheumatoid 120. Clinical features of axial spondyloarthritis 1039
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arthritis
Turid Heiberg, Anne-Lene Sand-Svartrud, Rikke Helene Moe, and Tore K. Kvien
869
Sofia Ramiro and Victoria Navarro-Compán
121. Pathogenesis and pathophysiology of axial spondyloarthritis

Dirk Elewaut, Elisabeth Gilis, and Ann-Sophie De Craemer
1045
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122. Genetics of axial spondyloarthritis 1051
ht 2 ou Matthew A. Brown and Huji Xu
,
123. Animal models of spondyloarthritis 1056

Volume Two
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Barbara Neerinckx and Margot Van Mechelen
124. Imaging in spondyloarthritis 1061

Xenofon Baraliakos, David Kiefer, and Jürgen Braun
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SECTION 8 125. Management of axial spondyloarthritis

Denis Poddubnyy
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126. Classification and epidemiology of psoriatic arthritis 1087

Pediatric Rheumatology
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M. Elaine Husni and Alexis R. Ogdie-Beatty
103. Evaluation of children with rheumatologic complaints 875

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127. Clinical features of psoriatic arthritis 1092

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Nora G. Singer and Karen B. Onel Laure Gossec
104. Classification and epidemiology of juvenile idiopathic arthritis 884 128. Extraarticular manifestations and comorbidities in psoriatic
Kirsten Minden arthritis 1100
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Lourdes M. Perez-Chada and Joseph F. Merola

105. Clinical features of juvenile idiopathic arthritis 894
Ellen B. Nordal, Marite Rygg, and Anders Fasth 129. Etiology and pathogenesis of psoriatic arthritis 1108
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Monica Guma, Christopher T. Ritchlin, and Dennis McGonagle

106. Etiology and pathogenesis of juvenile idiopathic arthritis 907
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Robert A. Colbert 130. Animal models of psoriatic arthritis 1118

Rik J. Lories and Barbara Neerinckx
107. Management of juvenile idiopathic arthritis 913
o
Roberta A. Berard, Philip J. Hashkes, and Ronald M. Laxer 131. Management of psoriatic arthritis 1122
Douglas J. Veale and Carl Orr
108. The juvenile-onset spondyloarthropathies 929
Pamela F. Weiss and Judith A. Smith
109. Systemic autoimmune rheumatic diseases in children 936

Joyce C. Chang, Suzanne C. Li, Scott M. Lieberman, Dawn M. Wahezi, and Jay J. Mehta
110. Rehabilitation and psychosocial issues in juvenile SECTION 11

idiopathic arthritis 951
Sabrina Cavallo Systemic Lupus Erythematosus and Related Diseases
132. Epidemiology and classification of systemic lupus erythematosus 1131
Candace H. Feldman and Karen H. Costenbader
SECTION 9 133. Preclinical features of systemic lupus erythematosus

Judith A. James
1139
134. Clinical features of systemic lupus erythematosus 1147

Infection-Related Rheumatic Diseases Vaneet K. Sandhu, Michael H. Weisman, Daniel J. Wallace, and Karina Torralba
135. Genetics of systemic lupus erythematosus 1166

A. Infectious Arthritis Viktoryia Laurynenka, Leah C. Kottyan, Jennifer A. Kelly, and John B. Harley
111. Bacterial native joint arthritis 961
Leo R.W. Kronberger, Tilman Obenhuber, and Ilker Uçkay 136. Immunopathology of systemic lupus erythematosus 1177
Jane E. Salmon and Vivette D. D’Agati
xxxiv Contents
137. Animal models of systemic lupus erythematosus 1192 159. Management of inflammatory muscle disease 1387
David I. Daikh Adam I. Schiffenbauer and Frederick W. Miller
138. Autoantibodies in systemic lupus erythematosus 1198 160. Metabolic, drug-induced, and other noninflammatory
Westley H. Reeves, Haoyang Zhuang, and Shuhong Han myopathies 1395
Lisa Christopher-Stine and George Stojan
139. Pathogenesis of systemic lupus erythematosus 1205
Sarthak Gupta and Mariana J. Kaplan
140. Drug-induced lupus 1211

Bruce Richardson
141. Assessing disease activity and outcome in systemic lupus SECTION 14

erythematosus 1220
Michelle Jung, Janet E. Pope, and Vibeke Strand The Vasculitides
142. Management of nonrenal and non–central nervous
161. Classification and epidemiology of vasculitis 1405
system lupus 1227 Richard A. Watts and Eleana Ntatsaki
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José A. Gómez-Puerta, Gerard Espinosa, and Ricard Cervera
162. Biology and immunopathogenesis of vasculitis 1418
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143. Management of central nervous system lupus 1235 Elisabeth Brouwer, Maria Sandovici, Coen A. Stegeman, Kornelis S.M. van der Geest, and
John G. Hanly, Antonina Omisade, and John D. Fisk Bram A. Rutgers
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144. Management of renal lupus 1241 163. Polyarteritis nodosa and Cogan syndrome 1427
c. .
Antonis Fanouriakis, George Bertsias, and Dimitrios T. Boumpas Lindsy Forbess
se se rm P
145. Systemic lupus erythematosus in pregnant patients and 164. Antineutrophil cytoplasm antibody–associated vasculitis 1438
neonatal lupus 1247 Raashid A. Luqmani and Tamir Malley
re El pe R
Aardra Rajendran, Tayseer G. Haroun, Prateek Chaudhary, and Megan E.B. Clowse
165. Takayasu arteritis 1449
146. Sjögren syndrome 1254 Carol A. Langford
s 3. t FO
Alan N. Baer and Gwenny M. Verstappen
166. Polymyalgia rheumatica and giant cell arteritis 1455
147. Antiphospholipid syndrome: pathogenesis, diagnosis, and Carlo Salvarani, Francesco Ciccia, and Nicolò Pipitone
management 1272
Mary-Carmen Amigo and Munther A. Khamashta 167. Behçet disease 1467
ig 20 ith OT Ahmet Gül
168. Kawasaki disease

Jane C. Burns and Adriana H. Tremoulet
1475
SECTION 12
N
ht 2 ou 169. IgA vasculitis (Henoch–Schönlein purpura) 1480
Seza Özen and Yelda Bilginer
170. Cutaneous vasculitis and panniculitis 1486

Systemic Sclerosis
,
ig se ES
Robert G. Micheletti, Luis Requena, and Jeffrey P. Callen
148. Classification and epidemiology of systemic sclerosis 1283 171. Cryoglobulinemia 1496
Bochra Jandali and Maureen D. Mayes Salvatore De Vita, Saviana Gandolfo, and Luca Quartuccio
w
yr u G
149. Clinical and serologic features of systemic sclerosis 1289 172. Primary angiitis of the central nervous system 1502
Christopher P. Denton and Voon H. Ong Jamal A. Mikdashi
op er A
Al ht s
150. Etiology and pathogenesis of systemic sclerosis 1302

Robert Lafyatis and John Varga
C th P
151. Outcomes measures in systemic sclerosis 1319

SECTION 15
©
Dinesh Khanna
LE
152. Management of systemic sclerosis 1326

Tracy M. Frech and Virginia D. Steen Other Systemic Illnesses
N MP
153. Emerging therapies for systemic sclerosis 1338

Oliver Distler and Anna-Maria Hoffmann-Vold 173. Adult-onset Still disease 1511
Elena Riera Alonso and Alejandro Olivé Marqués
lr
154. Raynaud phenomenon 1345

174. Monogenic autoinflammatory diseases 1519
o
Andrew R. Melville and Jill J.F. Belch

SA
Adriana A. de Jesus, Michael F. McDermott, Daniel L. Kastner, and Raphaela Goldbach-Mansky

155. Localized scleroderma and scleroderma-like syndromes 1351
175. Sarcoidosis 1547
o
Robert W. Simms
Jeffrey A. Sparks and Elizabeth V. Arkema
176. Relapsing polychondritis 1557

Susan Y. Ritter
SECTION 13 177. The systemic amyloidoses

Joel N. Buxbaum
1562
178. IgG4-related disease 1572

Inflammatory Muscle Disease Hisanori Umehara, Dai Inoue, and Mitsuhiro Kawano
156. Clinical features, classification, and epidemiology of 179. Immune-mediated complications of checkpoint inhibitors 1582
inflammatory muscle disease 1357 Alexa Simon Meara and Cassandra Calabrese
Rohit Aggarwal, Dana P. Ascherman, and Chester V. Oddis
180. The epidemiology of coronavirus disease 2019 (COVID-19)
157. Etiology and pathogenesis of inflammatory muscle and rheumatic disease 1589
disease (myositis) 1371 Jean W. Liew, Rebecca Grainger, Zachary S. Wallace, Jonathan S. Hausmann, Emily Sirotich,
Ingrid E. Lundberg Wendy Costello, Suleman Bhana, Paul Sufka, Pedro M. Machado, Jinoos Yazdany, and
Philip C. Robinson
158. Clinical significance of autoantibodies in inflammatory
muscle disease 1381
Kathleen D. Kolstad, Audra Horomanski, Anna Postolova, Lorinda Chung, and David F. Fiorentino
Contents xxxv
SECTION 16
204. Osteomalacia, rickets, and renal osteodystrophy 1796
Marciana L. Laster, Isidro B. Salusky, and Eva S. Liu
205. Paget disease of bone 1803

Osteoarthritis Laëtitia Michou and Jacques P. Brown
181. Epidemiology and classification of osteoarthritis 1595

Amanda E. Nelson
182. Local and systemic risk factors for incidence and

progression of osteoarthritis
Leena Sharma
1605 SECTION 19
183. Clinical features of osteoarthritis 1614 Other Arthropathies and Miscellaneous Disorders
Joel A. Block and Anne-Marie Malfait
206. Diffuse idiopathic skeletal hyperostosis 1811
184. Animal models of osteoarthritis 1620 Geoffrey O. Littlejohn
Isabell S. von Loga and Tonia L. Vincent
. In ion T
207. Neuropathic arthropathy 1818
185. Pathogenesis and pathology of osteoarthritis 1628 Dimitrios G. Kassimos and Paul Creamer
ed er s IN
Jay Ghadiali, Edward F. DiCarlo, and Carla R. Scanzello
208. Osteonecrosis 1824
186. Genetics and epigenetics of osteoarthritis 1645 Timothy McAlindon and John A. Carrino
rv vi is R
c. .
Matlock A. Jeffries
209. Rheumatoid manifestations of endocrine and metabolic
187. Imaging of osteoarthritis 1652 diseases and treatments 1833
se se rm P
Kiran Khokhar, Andrew J. Barr, Claire Y.J. Vandevelde, Andrew J. Grainger, and Philip G. Conaghan Katherine P. Pryor and Simon M. Helfgott
188. Assessment of the patient with osteoarthritis and 210. Hemophilia-associated arthritis 1840
re El pe R
measurement of outcomes 1667 Matthew J.S. Parker and Jane F. Bleasel
Lauren K. King, Aileen M. Davis, and Gillian A. Hawker
s 3. t FO
211. Rheumatologic manifestations of hemoglobinopathies 1848
189. Preclinical and early osteoarthritis 1673 Daniela Garelick, Hannah du Preez, and David Isenberg
Virginia Byers Kraus
212. Hemochromatosis 1853
190. Management of osteoarthritis 1679 Pascal Richette and Augustin Latourte
ig 20 ith OT
Sharon L. Kolasinski and Margreet Kloppenburg
191. Emerging treatments for osteoarthritis

Francis Berenbaum
1684
213. Gaucher disease
Philippe Orcel, Luc Pijnenburg, and Rose-Marie Javier
214. Digital clubbing and hypertrophic osteoarthropathy

1857
1863
N
ht 2 ou Manuel Martínez-Lavín and Carlos Pineda
215. Miscellaneous arthropathies 1868

,
SECTION 17
Thomas Bardin and Jonathan Kay
ig se ES
216. Heritable connective tissue disorders 1882

B. Paul Wordsworth and M. Kassim Javaid
Crystal-Related Arthropathies 217. Hypermobility syndrome 1902
w
yr u G
Jacqui Clinch and Valerie J. Rogers

192. Epidemiology and classification of gout 1693
Hyon K. Choi 218. Bone tumors 1907.e1
op er A
Al ht s
Edward F. McCarthy, Alan L. Schiller, Harriet Branford White, and Andrew Bassim Hassan
193. Etiology and pathogenesis of gout 1700
C th P
Tanya J. Major and Nicola Dalbeth

©
194. Clinical features of gout 1713 Appendix: Classification and Diagnostic Criteria 1907.e17
LE
Naomi Schlesinger Lukas Haupt and Gerhard Witzmann
195. Management of gout and hyperuricemia 1716

Robert Terkeltaub Index I1
N MP
196. Calcium pyrophosphate deposition disease (pseudogout) 1724

Ann K. Rosenthal
lr
197. Basic calcium phosphate crystal deposition disease 1735

o
SA
John Stack and Geraldine M. McCarthy

o
SECTION 18
Metabolic Bone Disease
198. Epidemiology and classification of osteoporosis 1743
Christopher R. Holroyd, Elaine Dennison, and Cyrus Cooper
199. Clinical evaluation and clinical features of osteoporosis 1752

Stuart L. Silverman and Deborah T. Gold
200. Pathophysiology of osteoporosis 1760

Jeffrey M. Kroopnick
201. Biochemical markers of bone turnover in postmenopausal

osteoporosis 1765
Richard Eastell and Pawel Szulc
202. Management of osteoporosis 1774

Chad L. Deal and Abby G. Abelson
203. Glucocorticoid-induced osteoporosis 1788

Arthur N. Lau, Jonathan Hwang, and Jonathan D. Adachi
The skin in rheumatic disease
Markus Böhm • Thomas A. Luger • Jan Ehrchen 34
Key Points combination of specific and nonspecific skin changes in the presence of an
■ Skin is frequently involved in rheumatic diseases. associated skin disorder may establish the final diagnosis of a rheumatic dis-
ease. Description of the skin lesions encountered in patients with rheumatic
. In ion T
■ Skin manifestations can be hallmark features in rheumatic diseases, especially lupus
erythematosus, dermatomyositis, and systemic sclerosis.
diseases requires precise terminology. Box 34.1 lists and explains common
ed er s IN
dermatologic terms encountered in this chapter.
■ Skin changes in rheumatic diseases are specific when characterized by a distinct
A minimally invasive procedure may be helpful to determine the nature of
clinical and histopathologic picture.
a skin lesion in patients with rheumatic disease. Although most skin lesions
rv vi is R
c. .
■ Nonspecific skin changes occur in a variety of diseases but not exclusively in a
can easily be assessed by punch biopsies, involvement of deeper skin layers
distinct rheumatic disorder.
such as in lupus panniculitis requires deep incisional biopsies to not miss
se se rm P
■ Skin manifestation can be a preceding sign of internal organ involvement and can the diagnosis. Whereas routine processing of skin biopsy specimens with
alert the clinician to a different course, therapeutic approach, and prognostic outcome paraformaldehyde fixation is usually sufficient to establish the diagnosis
re El pe R
in a patient with rheumatic disease. by histopathology, cryopreservation is needed to visualize immunoglobulin
deposits by specific staining. It is important to note that immunosuppressive
s 3. t FO
INTRODUCTION or immunomodulatory treatment (systemic and topical) can mask the natu-
ral histopathologic picture of a specific skin lesion. Because of the turnover
Skin changes occur in a variety of rheumatic diseases and are of relevance rate of human epidermis, cessation of any such treatment for at least 3 weeks
for clinicians dealing with such diseases for several reasons. First, skin can is recommended before skin biopsy.
ig 20 ith OT
be the initial site of involvement in a rheumatic disease, thereby providing
the physician with important clues to the correct diagnosis. Second, skin
involvement in a rheumatic disease may serve as an easy-to-access indica-
tor of both systemic involvement and prognostic outcome of the disorder.
MAJOR SYSTEMIC CONNECTIVE TISSUE
N
Third, because skin is the outermost organ of the body, disease burden and
ht 2 ou DISORDERS
impaired quality of life may be substantial in patients with rheumatic disease
SYSTEMIC LUPUS ERYTHEMATOSUS
,
with skin involvement. Fourth, skin changes may be induced in a patient

ig se ES
with rheumatic disease after therapy. The rapid advancement in the field of The key dermatologic signs of SLE are acute and chronic cutaneous lesions,
biologics and targeted therapies (e.g., kinase inhibitors or biologics) for the oral ulcers, and nonscarring alopecia as listed in the Systemic Lupus
treatment of rheumatic diseases requires pharmacovigilance for the skin as Erythematosus International Collaborating Clinics (SLICC) classification
w
yr u G
a frequent site of adverse effects. Finally, elucidation of the pathobiology of criteria (Box 34.2).1 The diversity of chronic LE skin lesions is unfortunately
skin manifestations can provide important clues into the pathogenesis of not well reflected in the 2019 ACR-EULAR classification criteria, which
op er A
rheumatic disorders, possibly promoting novel therapeutic approaches. include only subacute-cutaneous and discoid lupus lesions.2 Importantly, all
Al ht s
This chapter describes skin manifestations of the major systemic connec- of the cutaneous LE (CLE) lesions listed in Box 34.2 may occur in patients
C th P
tive tissue disorders: systemic lupus erythematosus (SLE), dermatomyositis with SLE. CLE, localized or generalized, can involve the epidermis, dermis,
(DM), systemic sclerosis (SSc), and Sjögren syndrome (SjS). This is fol- or subcutaneous fat of the skin.
©
LE
lowed by a variety of other systemic rheumatic diseases: rheumatoid arthritis Skin involvement is the second most common manifestation of SLE after
(RA), psoriatic arthritis (PsA), systemic-onset juvenile rheumatoid arthritis arthralgias. In approximately 25% of patients with SLE, skin is the first site
(SOJRA), and relapsing polychondritis (RP). The chapter starts with a sec- of disease involvement. The majority of patients with SLE develop skin
tion describing the general approach to patients with skin manifestations of lesions during the course of their disease. Some patients with SLE have no
N MP
a rheumatic disease. signs of skin involvement, a condition called lupus sine lupo.
Classification of the various forms of CLE remains challenging. The dif-
lr
ferent subtypes of CLE can occur both in patients with SLE and in patients
APPROACH TO THE PATIENT
o
SA
with no systemic involvement.

To assess skin involvement of a patient with rheumatic disease, a full-body Sontheimer and coworkers originally divided LE-specific skin disease
o
inspection, including the scalp, anogenital area, and mucous membranes, based on its acuity into acute CLE (ACLE), subacute CLE (SCLE), and
should always be performed because the skin manifestations of rheumatic chronic CLE (CCLE) (Box 34.3).3 These subtypes were further specified
diseases often have a predilection for distinct body sites that can otherwise according to the extent of their skin involvement (local vs generalized),
easily be overlooked. Examples of such situations are mucosal lesions in morphology, and localization of the inflammatory infiltrate in the skin
the oral cavities of patients with lupus erythematosus (LE) or intertriginous (e.g., LE panniculitis indicating LE-specific infiltration of adipose tissue).
involvement by psoriasis in patients with arthritis. Inspection of all skin Importantly, in patients with SLE, different forms of LE-specific skin lesions
appendages (i.e., hair and nails) is also an integral part of any routine derma- can be present simultaneously (e.g., a butterfly rash as a manifestation of
tologic inspection. For example, nail changes can be an indicator of PsA, and localized ACLE plus chilblain LE as a variant of CCLE). All of these cutane-
scarring alopecia may be a disfiguring skin manifestation of LE. Full-body ous LE forms can be found in the SLICC classification criteria but in a more
inspection enables the physician to determine the precise extent and severity descriptive form to avoid the troublesome acronyms.
of skin involvement in a rheumatic disease. Scores to assess the extent and The hallmark skin lesion in patients with SLE is malar rash, which is
severity of skin involvement have been developed, for example, for LE, SSc, a reddish maculopapular eruption in a characteristic butterfly distribution
and psoriasis, and should be used to determine the disease dynamics and (“butterfly rash”) on the face. In most cases patients recall induction or exac-
monitor treatment efficacy. erbation of the rash by exposure to ultraviolet (UV) light, thus indicating
The skin changes in systemic rheumatic diseases are specific when they that photosensitivity is an important pathogenetic component. Importantly,
display characteristic and sometimes even pathognomonic features along lesion development is delayed after UV exposure (approximately 1 week).4
with a typical histopathology encountered only in a distinct rheumatic Lesions usually last from several days to weeks and heal without scarring.
disease. On the other hand, cutaneous manifestations are nonspecific and Occasionally, poikiloderma (characterized by dyspigmentation, prominent
occur in a diversity of rheumatic and nonrheumatic systemic diseases. It is blood vessels, and thinning of the skin) can occur. The malar rash may
also well established that some skin diseases have an increased incidence precede the multisystem involvement of SLE. Less common are general-
in patients with selected systemic rheumatic diseases. These dermato- ized forms (Fig. 34.1). Bullous and toxic epidermal necrolysis variants are
ses are best referred to as associated skin diseases. In some cases, only the fulminant forms of generalized ACLE in which a massive epidermal injury
271
272 SECTION 3 Approach to the Patient
BOX 34.1 FREQUENTLY USED DERMATOLOGIC TERMS BOX 34.3 CLASSIFICATION OF LUPUS ERYTHEMATOSUS–SPECIFIC
SKIN LESIONS
Erosion—a superficial tangential defect of the epidermis
Erythema—generalized erythema of the skin A. Acute cutaneous lupus erythematosus (ACLE)
Koebner phenomenon—induction of specific skin lesions by nonspecific trauma 1. Localized ACLE
such as scratching 2. Generalized ACLE
Macule—a localized discoloration of the skin; when the discoloration is red, it is 3. Toxic epidermal necrolysis–like ACLE
called erythema 4. Bullous ACLE
Onychodystrophy—disturbed growth of the nail plate B. Subacute cutaneous lupus erythematosus (SCLE)
Onycholysis—separation of the nail plate from the nail bed (hyponychium) 1. Annular
Papule, nodule, or plaque—a raised, localized, solid skin lesion; when the 2. Papulosquamous
raised lesion has spread horizontally, it is referred to as a plaque C. Chronic cutaneous lupus erythematosus (CCLE)
Pathergy phenomenon—induction of specific skin lesions by intracutaneous 1. Discoid lupus erythematosus (DLE)
injection of sterile NaCl or as a result of venipuncture a. Localized
Poikiloderma—a combination of hyperpigmentation, hypopigmentation, b. Generalized
. In ion T
telangiectasia, and skin atrophy 2. Hypertrophic or verrucous lupus erythematosus
Pruritus—itch 3. Lupus erythematosus tumidus
ed er s IN
Purpura or petechia—localized intradermal hemorrhage; when less than 3 mm 4. Lupus panniculitis or profundus
in diameter, it is called petechial 5. Chilblain lupus erythematosus
rv vi is R
c. .
Pustule—a vesicle filled with pus 6. DLE–lichen planus overlap
Sclerosis—induration of the skin
se se rm P
Adapted from Sontheimer RD. Skin manifestations of systemic autoimmune connective tissue disease:
Squama—localized area of abnormal shedding of the corneal layer of the diagnostics and therapeutics. Best Pract Res Clin Rheumatol 2004;18:429–62.
epidermis
re El pe R
Ulcer—a defect of the epidermis and deeper layers of the skin (dermis,
subcutaneous tissue); it inevitably leads to scar formation
s 3. t FO
Urtica or wheal—a transient raised skin lesion attributable to dermal edema;
the center of the lesion is pale and the borders are erythematous
Vesicle or bulla—a localized, raised lesion of the skin filled with exudate, either
serous or hemorrhagic fluid; when larger than 0.5 cm in diameter, a vesicle
ig 20 ith OT
is called a bulla
BOX 34.2 CUTANEOUS LE SIGNS AS LISTED IN THE SLICC

N
ht 2 ou
CLASSIFICATION CRITERIA
1. Acute cutaneous lupus including lupus malar rash
,
ig se ES
bullous lupus
toxic epidermal necrolytic variant of SLE
maculopapular lupus rash
w
photosensitive lupus rash

yr u G
or subacute cutaneous lupus FIG. 34.1 Generalized acute cutaneous lupus erythematosus. Note the typical distri-
2. Chronic cutaneous lupus including classical discoid rash (localized or
op er A
bution with sparing of the knuckles.

Al ht s
generalized)
C th P
hypertrophic (verrucous) lupus

lupus panniculitis (profundus)
©
mucosal lupus
LE
lupus erythematosus tumidus

chilblain lupus
discoid lupus/lichen planus overlap
N MP
3. Oral ulcers
4. Nonscarring alopecia
lr
Data adapted from Petri M, Orbai AM, Alacron GS, et al. Derivation and validation of the Systemic
o
SA
Lupus Erythematosus International Collaborating Clinics classification criteria for systemic lupus
erythematosus. Arthritis Rheum. 2012;64:2677–2686.
o
occurs, possibly because of severe alterations in the dermoepidermal junc-

tion and subsequent apoptosis. Oral lesions are a common mucocutaneous
manifestation in patients with SLE. Typically, they consist of painful aph- FIG. 34.2 Subacute lupus erythematosus (annular subtype). Note the characteristic
thoid lesions and ulcerations, especially on the lips and buccal and pala- localization on the upper part of the trunk (V shape).
tal mucosa, but they may be localized elsewhere in the oral cavity. Palatal
lesions may be asymptomatic.
Patients with clinical features of SCLE usually have circulating anti-Ro but hypopigmentation or depigmentation as a result of postinflammatory
and anti-La antibodies and display the HLA-B8 and HLA-DR3 haplotype. destruction of epidermal melanocytes is a common complication during the
SLCE may be induced by drugs, including antihypertensives, antifungals, healing process of these skin lesions (Fig. 34.3), especially in patients with
thiazide diuretics, angiotensin-converting enzyme inhibitors, calcium chan- darker skin phenotypes. A substantial proportion of patients with SCLE
nel blockers, and gemcitabine.5 This drug-induced type of SCLE does not exhibit mild systemic symptoms, especially arthralgias and musculoskeletal
differ clinically, histopathologically, or immunologically from idiopathic complaints. Severe organ manifestation is less frequent; however, patients
SCLE. Two clinical variants of SCLE have been identified: an annular (or with SLCE have an increased risk to develop SLE.
arcuate) variant consisting of slightly raised erythema with central clearing The classical skin lesion of CCLE is the discoid rash. It may be localized
and a papulosquamous variant consisting of psoriasis-like or eczema-like or generalized and consists of erythematous discoid plaques that become
lesions, both typically located on UV-exposed skin, including the lateral hyperkeratotic, finally leading to atrophy and scarring. Scarring alopecia
aspects of the face, the V of the neck (often with sparing of the area under may develop on the scalp. CCLE occurs more often in Black individuals
the chin), the upper ventral and dorsal part of the trunk (Fig. 34.2), and the than in White individuals. Dyspigmentation, including hypopigmentation
dorsolateral aspects of the forearms. SCLE lesions never lead to scarring, and hyperpigmentation, is common and more commonly encountered in
CHAPTER 34 The skin in rheumatic disease 273
. In ion T
FIG. 34.3 Residual vitiligo-like skin lesions in a patient with subacute cutaneous FIG. 34.4 Lupus erythematosus tumidus. Note the urticarial plaques on the face
ed er s IN
lupus erythematosus. and neck.
rv vi is R
c. .
patients with darker skin phototypes. Discoid lesions have a predilection for
se se rm P
the face, ears, and neck but may be widespread without a clear-cut relation-
ship to UV exposure. Disfigurement can be a serious problem, especially in
re El pe R
patients with facial involvement. Mucosal membranes, including the lips,
mucosal surfaces of the mouth, nasal membranes, conjunctivae, and genital
s 3. t FO
mucosa, may also be involved, with characteristic discoid lesions resembling
leukoplakia. Although DLE is considered primarily a form of CLE without
systemic involvement, patients with SLE can have classic DLE lesions. Long-
term follow-up of patients with DLE is also necessary because according to a
ig 20 ith OT
number of studies, SLE can develop in 5% to 17% of patients in the course of
the disease, especially in patients with generalized skin lesions and positive
ANA titers.
As outlined in Boxes 34.2 and 34.3, several other subtypes of chronic
N
cutaneous lupus can occur in patients with SLE.
ht 2 ou
In hypertrophic/verrucous CCLE, epidermal hyperkeratosis is prominent
,
and results in lesions with thickening of the stratum corneum. FIG. 34.5 Chilblain lupus erythematosus of the toes.
ig se ES
Lupus erythematosus tumidus is a rarer variant of CLE characterized

by photosensitive erythematous, sometimes urticarial plaques and nodules
without epidermal hyperkeratosis or follicular plugging. Lesions are usually
w
yr u G
located on the face, upper part of the trunk, and extremities (Fig. 34.4). The
majority of patients with LE tumidus do not have antinuclear antibodies, involvement, LE-specific histologic changes can be subtle. ACLE lesions
op er A
and the diagnosis relies mainly on the clinical and histomorphologic picture. show vacuolar degeneration of the dermoepidermal junction, dead kerati-
Al ht s
Because the course and prognosis of LE tumidus is generally more favorable nocytes (“Civatte bodies”), and a sparse lymphohistiocytic infiltrate of the
C th P
than in other subtypes of CLE, this CLE may be considered as a separate upper dermis. Dermal blood vessels are dilated with extravasation of eryth-
subtype in the spectrum of cutaneous manifestation of LE (“intermittent rocytes. In SCLE, these findings are often associated with epidermal atro-
©
LE
subtype of CLE”).6 phy. The lymphohistiocytic infiltrate is located in the upper dermis with an
Lupus erythematosus panniculitis is a chronic CLE subtype consisting interface and perivascular pattern. Classic DLE lesions have additional epi-
of intense inflammation within the adipose tissue of the skin that results in dermal hyperkeratosis and thickening of the dermoepidermal and follicular
indurated plaques and lipoatrophy. Lesions are commonly seen on the face, basement membranes. The lymphohistiocytic infiltrate is often prominent
N MP
proximal parts of the extremities, upper part of the trunk, and buttocks and and involves hair follicles, which may also show hyperkeratotic plugging.
can be disfiguring. When the overlying dermis and epidermis are involved Mucin is usually deposited in the dermis. Deeper forms of CCLE are charac-
lr
in LE panniculitis, it is called LE profundus. In the majority of cases, LE pro- terized by a lymphohistiocytic infiltrate situated in the lower dermis, often
o
SA
fundus is not associated with any systemic organ involvement.7 with mucin deposits (LE tumidus), but in lupus panniculitis the infiltrate is
Another variant of CCLE is chilblain LE, which denotes pernio-like skin located primarily in the subcutaneous fat tissue. Direct immunofluorescence
o
lesions (i.e., red to violaceous plaques located on the distal parts of the extrem- (DIF) can be used to assess the presence of immunoglobulin (IgG, IgM, and
ities—fingertips, toes, and occasionally other parts of the body) that are typi- rarely IgA) and complement (C3) along the dermoepidermal junction in
cally induced and aggravated by exposure to cold (Fig. 34.5). These patients frozen sections of CLE lesions. In patients with SLE, this test (“lupus band
should be monitored carefully because SLE may develop in up to 24%.8 test”) is typically positive even in nonlesional, sun-protected skin. However,
In rare cases, patients with SLE can present with tense blisters resem- DIF studies currently provide little benefit to the overall diagnosis and clas-
bling autoimmune bullous diseases. Autoantibodies directed against colla- sification of LE and may be used only to discriminate between CLE and skin
gen 7 can be detected by immunofluorescence staining in skin lesions of diseases with similar histopathologic findings.
these patients. Skin lesions can precede development of systemic disease The differential diagnosis of ACLE lesions includes erythema solare (sun-
manifestations.9 burn), photoallergic and phototoxic drug eruptions, DM, atopic eczema,
In the past, CLE disease activity has been assessed by various outcome seborrheic dermatitis, contact eczema, and rosacea. SCLE lesions need to
measurements and scores. A Revised CLE Disease Area and Severity Index be distinguished from photoallergic and phototoxic drug eruptions, as well
(RCLASI) has been introduced.10 This modified outcome instrument now as from other forms of annular erythemas (erythema annulare centrifugum,
includes the various CLE subtypes, as well as disease activity parameters erythema gyratum repens, granuloma annulare, atopic dermatitis, psoriasis,
(e.g., edema, scaling, hypertrophy, or dyspigmentation). The RCLASI may and tinea). Leukoderma in patients with SCLE must not be mistaken for vit-
be used especially in clinical trials of patients with CLE to precisely assess iligo and hyperpigmented skin lesions in patients with chronic DLE (CDLE)
skin involvement. have to be distinguished from other forms of hyperpigmentary skin diseases.
Histopathologic examination of a biopsy specimen from specific skin In addition to the previously described LE-specific skin lesions, a vari-
lesions is recommended for a correct diagnosis in a patient with LE. ety of nonspecific skin signs and associated skin diseases can be present in
However, proper classification of the various CLE subtypes is based primar- patients with SLE. These include vascular changes such as nail-fold abnor-
ily on macroscopic skin morphology, while the diagnosis of SLE relies on malities (large and tortuous capillaries together with areas of avascularity),
the overall clinical picture, including possible other organ manifestations, as well as more serious complications such as vasculitis (leukocytoclas-
laboratory and autoimmune serologic analysis. In acute forms of cutaneous tic vasculitis, urticarial vasculitis, nodular vasculitis) and other forms of

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Vice Dean for Education Consultant Rheumatologist

Health Elena Riera Alonso, MD Professor of Medicine

Professor Rheumatologyst Division of Rheumatology

Chapter 203, Glucocorticoid-induced osteoporosis Chapter 146, Sjögren syndrome

Rohit Aggarwal, MD M Bioeth Xenofon Baraliakos, MD, PhD

University of Pittsburgh School of Medicine, Rheumatology Service Rheumatology

Shizuo Akira, MD, PhD Martin Aringer, MD Thomas Bardin, MD

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Medical Affairs Chapter 90, Clinical features of rheumatoid arthritis

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University of Turin Medical School

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in rheumatology Brigham and Women’s Hospital Professor

Department of Rheumatology and Clinical

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Chapter 82, The hip

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Associate Professor of Medicine

Duke University Medical Center

Raymond K. Cross, MD, MS

Chapter 145, Systemic lupus erythematosus in Carlos Eduardo de Barros Branco, MD

Center for Osteoporosis and Metabolic Bone

Barts Health NHS Trust Stephen Eyre, PhD

Professor of Medicine The University of Manchester

Aurora, Colorado Department of Orthopaedic Surgery

Harvard Medical School Assistant Professor of Internal Medicine-Rheumatology

Paul F. Dellaripa, MD Cambridge Massachusetts Medical School National and Kapodistrian

Division of Rheumatology Boston, Massachusetts Athens, Greece

Chapter 37, The lungs in rheumatic disease

Professor of Bone Metabolism Senior Investigator

Professor of Medicine Elisabeth Gilis, PhD

Dermatology University Hospitals of Geneva Ghent University

Stanford University School of Medicine Geneva, Switzerland Department of Rheumatology, Molecular

in inflammatory muscle disease Ghent, Belgium

Translational Immunology Section axial spondyloarthritis

Senior Clinical Lecturer National Institute of Arthritis and Musculoskeletal

University of Birmingham Bethesda, Maryland Psychiatry & Behavioral Sciences

Department of Rheumatology Duke University Medical Center

Susan M. Goodman, MD Ahmet Gül, MD Philip J. Hashkes, MD, MSc

Immunology Appendix: Classification and diagnostic criteria

Chapter 138, Autoantibodies in systemic lupus

Consultant Radiologist erythematosus Boston Children’s Hospital

Cambridge, United Kingdom John G. Hanly, MD, FRCP(C) Immunology

Chapter 187, Imaging of osteoarthritis