Firestein & Kelley’s Textbook of Rheumatology, 2-Volume Set

12th Edition - July 24, 2024
Imprint: Elsevier
Editors: Gary S. Firestein, Iain B. McInnes, Gary Koretzky, Ted Mikuls, Tuhina Neogi, James R. O'Dell
Language: English
Hardback ISBN:
9 7 8 - 0 - 3 2 3 - 9 3 5 4 0 - 1
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 3 5 0 5 1 - 1
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 3 5 9 0 - 6

**Selected for 2025 Doody’s Core Titles® with "Essential Purchase" designation in Rheumatology**With its comprehensive, global coverage of all aspects of diagnosis, screenin… Read more

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**Selected for 2025 Doody’s Core Titles® with "Essential Purchase" designation in Rheumatology**

With its comprehensive, global coverage of all aspects of diagnosis, screening, and treatment in both adults and children, Firestein & Kelley’s Textbook of Rheumatology remains your reference of choice in this evolving field. The fully revised 12th Edition retains the user-friendly, full color format, providing in-depth guidance in rheumatology with an ideal balance of basic science and clinical application. New editors, new chapters, and new illustrations keep you fully up to date on recent advances in genetics and the microbiome, current therapies, and other rapid changes in the field.

Instructions for online access
Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Preface
Volume I
Part 1. Structure and Function of Bone, Joints, and Connective Tissue
1. Developmental Biology, Organization, and Function of the Synovial Joints
Classification of Joints
Developmental Biology of Limb Diarthrodial Joints and Skeletal Elements
Organization and Physiology of the Mature Joint
Conclusion
2. Synovium
Structure
Function
Conclusion
3. Cartilage and Chondrocytes
Introduction
Cartilage Structure
Structure–Function Relationships of Cartilage Matrix Components
Morphology, Classification, and Normal Function of Chondrocytes
Interactions of Chondrocytes With the Extra-cellular Matrix
Angiogenic and Antiangiogenic Factors
Roles of Growth and Differentiation (Anabolic) Factors in Normal Cartilage Metabolism
Epigenetic Regulation of Cartilage Homeostasis
Role of the Chondrocyte in Cartilage Pathology
Conclusion
4. Development and Biology of Bone
Structure and Composition of Bone
Bone Remodeling
Conclusion
5. Muscle Anatomy, Physiology, and Biochemistry
Introduction
Structure
Muscle Architecture
Physiology
Energy and Biochemistry
Plasticity
Conclusion
6. Biomechanics
Introduction
Kinematics
Kinetics
Joint Mechanics
Joint Constraint and Stability
Mechanical Loading on Tendon
Mechanical Loading on Bursae
Conclusion
7. Regenerative Medicine and Tissue Engineering
Introduction
Extrinsic Repair: Current Therapeutic Interventions
Cell Therapy for Osteoarthritis
Intrinsic Repair
Conclusion
8. Proteinases and Matrix Degradation
Introduction
Extra-cellular Matrix–Degrading Proteinases
Regulation of Proteinase Activity
Joint Tissue Destruction in Arthritis
Conclusion
Part 2. Cells Involved in Autoimmune Diseases and Inflammation
9. Dendritic Cells
Introduction
Dendritic Cell Subsets and Development
Dendritic Cell Maturation and Activation
Antigen Processing and Presentation
Impairment of Dendritic Cell Biology in Diseases
Immunotherapeutic Strategies and Clinical Trials
Conclusion
10. Mononuclear Phagocytes
Introduction
Macrophage Origin: Nature Versus Nurture
Mononuclear Phagocytes in Rheumatoid Arthritis
Human Macrophage Heterogeneity: Where Do We Go From Here?
11. Neutrophils
Introduction
Neutrophils: Basic Principles
Neutrophil Functions
Heterogeneity
Role of Neutrophils, Low-Density Granulocytes, and Neutrophil Extra-cellular Traps in Rheumatic Diseases
Targeting Neutrophils and Neutrophil Extra-cellular Traps in Systemic Autoimmune Diseases
Conclusion
12. T Lymphocytes
Introduction
T Cell Development
Immunodeficiencies Resulting From Defects in T Cell Development
Peripheral Migration and Homeostatic Proliferation of T Cells
Activation of T Cells
Tolerance and Control of Autoreactive T Cells
T Cell Subsets
Inflammation Mediated by T Cells
Termination of T Cell Responses
Conclusion
13. B Cells
Introduction
Immunoglobulins: Structure and Function
Glycosylation
B Cell Development
B Cell Activation and Differentiation
Repertoire Selection
Molecular Triggers of Autoimmunity
Conclusion
14. Fibroblasts andFibroblast-like Synoviocytes
Introduction
What Is a Fibroblast?
Physiologic Characteristics and Functions of Fibroblasts
Role of Fibroblasts in Persistent Inflammation
Fibroblast-like Synoviocytes in Rheumatoid Arthritis
Lessons Learned From Cancer
Conclusion
15. Mast Cells and Basophils
Introduction
Mast Cells and Basophils in Ancient Innate Immunity
Distinguishing Features of Mast Cells and Basophils
IgE-Dependent Upregulation of FcεRI Expression and FcεRI-Dependent Function
Mast Cell and Basophil Heterogeneity
Genetic Approaches for Analyzing Mast Cell and Basophil Function
Immunoregulatory Functions of Mast Cells and Basophils
Biological Functions of Mast Cells and Basophils
Conclusion
16. Innate Lymphoid Cells and Natural Killer Cells
Introduction
Distinguishing Human ILCs and NK Cells
Target Recognition by NK Cells and Killer Immunoglobulin-like Receptors
Biology of ILCs and NK Cells
Role of NK Cells in Rheumatic Disease
Role of ILCs in Rheumatic Disease
Conclusion
17. Platelets and Megakaryocytes
Introduction
Platelet Structure
Platelet Production
Platelets and Hemostasis
Signaling Pathways in Platelet Activation
The Platelet as an Immune Cell
The Megakaryocyte as an Immune Cell
Platelets, Megakaryocytes, and Rheumatic Diseases
Conclusion
Part 3. Effector Mechanisms in Autoimmunity and Inflammation
18. Principles of Signaling
Introduction
Receptors With Enzymatic Activity
Receptors That Recruit Molecules With Enzymatic Activity
Sphingosine 1-Phosphate
Innate Receptor Signaling
Intra-cellular Receptor Signaling
Adaptor Molecules
Signaling Pathways
Transcription Factors
Conclusion
19. Innate Immunity
Introduction
Evolutionary Origins of Innate Immunity
Pathogen Recognition by the Innate Immune System
PAMPs and DAMPs: Patterns for Innate Immune Recognition
Effector Mechanisms of Innate Immune Responses
Influence of Innate Mechanisms on Adaptive Immunity
Disease Associations Involving Innate Immunity
Conclusions
20. Adaptive Immunity
Introduction
Phylogenetic Appearance of the Adaptive Immune System
Cardinal Features of the Adaptive Immune System
Cells of the Adaptive Immune System
Development of Adaptive Immune Cells
Anatomic Organization of the Peripheral Adaptive Immune System
Trafficking of Adaptive Immune Cells
Cell-to-Cell Interactions That Support Development of an Immune Response
Consequences of Failed Development or Activation of the Adaptive Immune System
Conclusion
21. Immune Tolerance and Autoimmunity
Introduction
Definition and Classification of Pathogenic Autoimmunity
Animal Models of Autoimmunity
Tolerance Mechanisms
Theories of Autoimmunity
Immunological Mechanisms of Tissue Inflammation and Dysfunction
Pathophysiology of Autoimmune Rheumatic Diseases
Genetics of Autoimmune Diseases
Sex and Autoimmunity
Microbial and Other Environmental Triggers
Conclusion
22. Pre-clinical Autoimmunity
Introduction
Defining Pre-classification Autoimmunity: More Than Just Semantics
Population Epidemiology of Autoimmunity
Type 1 Diabetes as a Paradigm for Pre-classification Autoimmunity
Pre-classification Systemic Autoimmune Disease
Conclusion
23. The Microbiome in Rheumatic Diseases
Introduction
Microbiome Analyses
The Microbiota in Rheumatic Diseases
Microbiota Therapies
Conclusion
24. Genetics of Rheumatic Diseases
Introduction
Evidence for a Genetic Component to Rheumatic Diseases
Study Design
Susceptibility Genes in Rheumatic Disease
Clinical Translation
Identification of High-Risk Groups
25. Epigenetics of Rheumatic Diseases
Introduction
Epigenetic Regulation
Epigenetics and the Immune Response
Challenges Faced in Translational Epigenetics Research
Epigenetics in Rheumatic Diseases
Integration of Epigenetic Data Streams and Clinical Applications
Conclusion
26. Complement System
Introduction
Functions of the Complement System
Terminology to Describe Complement and Its Activation Fragments
Activation Pathways
Regulation of Complement Activation
Receptors for Complement Fragments
Functions of the Complement System
Complement Deficiency
Targeted Complement Therapeutics
Complement in Rheumatic Diseases
Conclusion
27. Prostaglandins, Leukotrienes, and Related Compounds
Introduction
Biosynthesis of Eicosanoids
Products of the Cyclooxygenase Pathway
Eicosanoid Receptors
Platelet-Activating Factor
Eicosanoids as Regulators of Inflammation and Immune Responses
Modulation of Eicosanoid Synthesis by Administration of Precursor Fatty Acids
28. Angiogenesis
Introduction
Endothelial Cells
Angiogenesis
Regulators of Angiogenesis
Hypoxia, Cell Metabolism, and Angiogenesis
Angiogenic Mechanisms in Rheumatoid Arthritis and Spondyloarthropathies
Targeting Angiogenesis
Conclusion
29. Cytokines and Chemokines
Introduction
Cytokine Receptors
Regulation of Cytokine Expression
Effector Function of Cytokines
Chemokines
Conclusion
30. Neuronal Mechanisms of Pain and Inflammation
Introduction
Peripheral Pain Pathways
Pain-Resolving Pathways in the Periphery
Interactions Between Peripheral Pain Pathways and the CNS
Systemic Factors Contributing to Pain Heterogeneity in Rheumatic Diseases
Efferent Actions of Nociceptive Pathways
Clinical Scenarios
Conclusions
Part 4. Broad Issues in the Approach to Rheumatic Disease
31. Clinical Research Methods in the Rheumatic Diseases
Data Sources for Research in Rheumatology
Measures of Occurrence
Measures of Association
Study Designs
Clinical Trial Considerations
Common Sources of Bias
Effect Measure Modification, Interaction, and Heterogeneity
Surveillance and Screening
Conclusion
32. Epidemiology and Impact of Rheumatic Diseases
Epidemiology of Arthritis and Other Rheumatic Diseases
Arthritis-Attributable Costs
Public Health Approaches to Arthritis Self-Management
Conclusion
33. Assessment of Health Outcomes
Introduction
Types of Outcomes
Evaluation and Endorsement of Outcomes
Review of Disease-Specific Outcomes
Measures That Address Symptoms and Individual Health Domains
Imaging and Biomarker Outcomes
Health Outcomes in Real-World Settings
Conclusion
34. Biomarkers in Rheumatology
Biomarker Definitions and Applications
Defining Patient Heterogeneity
Pitfalls in Translation From Biomarker Discovery to Clinical Utility
Surrogate Biomarkers
Companion Diagnostics Versus CLIA Regulatory Routes
Safety Biomarkers
Biomarkers in Rheumatic Diseases
Biomarkers in Osteoarthritis
Biomarkers in Rheumatoid Arthritis
Biomarkers in Systemic Lupus Erythematosus
Next Horizons for Biomarkers
35. Occupational, Environmental, and Recreational Musculoskeletal Disorders
Introduction
Occupation-Related Musculoskeletal Disorders
Occupation-Related Rheumatic Diseases
Recreation- and Sports-Related Musculoskeletal Disorders
Performing Arts–Related Musculoskeletal Disorders
36. Cardiovascular Risk in Inflammatory Rheumatic Disease
Introduction
Biologic Mechanisms: Relationship Between Inflammation and Cardiovascular Disease
Cardiovascular Morbidity and Mortality in Rheumatoid Arthritis and Systemic Lupus Erythematosus
Risk Factors for Cardiovascular Disease
Cardiovascular Mortality, Morbidity, and Risk Factors in Other Rheumatic Diseases
Managing Cardiovascular Risk in Rheumatic Disease
Cardiovascular Disease Risk Assessment
Conclusion
37. Cancer Risk in Rheumatic Diseases
Introduction
Malignancy in Autoimmune Rheumatic Diseases
Rheumatoid Arthritis
Systemic Lupus Erythematosus
Systemic Sclerosis (Scleroderma)
Idiopathic Inflammatory Myopathy
Sjögren’s Syndrome
Vasculitis
Seronegative Spondyloarthritis
Cancer Risks Associated With Anti-rheumatic Drug Therapies
Conventional (Traditional) Nonbiologic DMARD Therapy
Biologic Response Modifiers
Immune Checkpoint Inhibitors
Cancer Screening in Patients With Rheumatic Disease
Conclusion
38. Occupational Therapy, Physical Therapy, and Rehabilitation
Introduction
Role of Rehabilitation in Rheumatology
Components of Rehabilitation
Incorporating PT/OT Into Rheumatology Practice
Conclusion
39. General Principles of Pregnancy and Rheumatic Disease: Pre-pregnancy Assessment
Introduction
Interplay of Rheumatic Disease and Pregnancy Physiology
General Principles of Pregnancy and Rheumatic Disease: Pre-pregnancy Assessment
Systemic Lupus Erythematosus
Overlap Syndromes and Undifferentiated Connective Tissue Disease
Sjögren’s Syndrome
Antiphospholipid Syndrome
Inflammatory Arthritis
Inflammatory Myositis
Systemic Sclerosis
Vasculitis
Medications During Pregnancy and Breastfeeding
Paternal Medication Use
Pregnancy-Related Issues for Rheumatic Disease Patients
Conclusion
Part 5. Evaluation of Generalized and Localized Symptoms
40. History and Physical Examination of the Musculoskeletal System
History in a Patient With Musculoskeletal Disease
Systematic Method of Physical Examination
Recording the Joint Examination
Interpreting the Joint Examination
Examination of Specific Joints
41. Ultrasound in Rheumatology
Introduction
Technical Aspects
Artifacts
Examination Technique
Ultrasound in Rheumatology Definitions
Rheumatoid Arthritis
Osteoarthritis
Crystalline Arthropathy
Spondyloarthritis
Polymyalgia Rheumatica
Giant Cell Arteritis
Sjögren’s Syndrome
Fibrotic Diseases
Non-inflammatory Conditions
Pediatric Rheumatology
Ultrasound in Rheumatology Intervention
Conclusion
42. Evaluation of Monoarticular and Polyarticular Arthritis
Introduction
Approach to the Patient With Arthritis
Differential Diagnosis
Formal Criteria and Their Role in Clinical Diagnosis
Preliminary Diagnoses, Working Diagnoses, Presumptive Treatments, Reassessments, and Future Perspectives
43. Skin and Rheumatic Diseases
Introduction
Psoriasis
Reactive Arthritis
Rheumatoid Arthritis
Juvenile Rheumatoid Arthritis and Still’s Disease
Lupus Erythematosus
Neonatal Lupus Syndrome
Sjögren’s Syndrome
Dermatomyositis
Morphea, Systemic Sclerosis, and Other Sclerosing Conditions
Primary Vasculitis Involving the Skin
Infections
Panniculitis
Relapsing Polychondritis
Infiltrative Diseases
Miscellaneous Skin Diseases and Arthritis
44. The Eye and Rheumatic Diseases
Introduction
Ocular Anatomy and Physiology
Ocular Immune Response
Uveitis
Scleritis and Corneal Melt
Orbital Disease
Optic Neuritis
Medication-Related Ocular Toxicity
Conclusion
Part 6. Differential Diagnosis of Regional and Diffuse Musculoskeletal Pain
45. Neck Pain
Epidemiology
Anatomy
Axial Neck Pain
Radiculopathy and Myelopathy
Infection and Neoplasm
Clinical Features
Diagnostic Evaluation
Differential Diagnosis and Treatment
46. Shoulder Pain
Introduction
Anatomy and Function
Diagnosis
Intrinsic Factors Causing Shoulder Pain
Extrinsic or Regional Factors Causing Shoulder Pain
47. Low Back Pain
Introduction and Epidemiology
Anatomy
Clinical Evaluation
Differential Diagnosis
Treatment
Outcome
Conclusion
48. Hip and Knee Pain
Introduction
Knee Pain
Hip Pain
49. Foot and Ankle Pain
Introduction
Functional Anatomy and Biomechanics
Diagnostic Evaluation
Imaging
Differential Diagnosis of Ankle Pain
Differential Diagnosis of Foot Pain
Nonsurgical Treatment
Surgical Treatment
Conclusion
50. Hand and Wrist Pain
Introduction
Patient Evaluation
Physical Examination
Common Causes of Hand and Wrist Pain
51. Temporomandibular Joint Disorders
Introduction
Congenital and Acquired Temporomandibular Joint Disorders
Temporomandibular Joint Diseases
Arthralgia
Masticatory Muscle Pain
Neuroplasticity, Nociplasticity, and Chronic Pain
TMD Management Strategies
Conclusion
52. Fibromyalgia
Introduction
Historical Perspective
Diagnostic Criteria
Epidemiology
Clinical Features
Differential Diagnosis and Comorbidities
Assessment of Severity
Mechanisms of Disease
Social and Psychological Factors
Treatment Approaches
Outcome
Part 7. Diagnostic Tests and Procedures in Rheumatic Diseases
53. Synovial Fluid Analyses, Synovial Biopsy, and Synovial Pathology
Introduction
Synovial Fluid Analysis
Biochemical Analysis of Synovial Fluid
Synovial Biopsy
Synovial Pathology
Synovial Immunohistology
Conclusion
54. Arthrocentesis and Injection of Joints and Soft Tissues
Introduction
Indications, Contraindications, and Potential Complications of Arthrocentesis and Soft Tissue Injections
Drugs and Preparations Used for Injection
Procedures Description
Upper Limb Injections
Lower Limb Injections
Soft Tissue Injections: Upper Limbs
Soft Tissue Injections: Lower Limbs
Conclusion
55. Anti-nuclear Antibodies
Introduction
Methods of Detection
Relevance of Anti-nuclear Antibodies to Disease Pathogenesis
Diseases Primarily Associated With Anti-nuclear Antibodies
Specific ANA Clinical Scenarios
Recommendations for Anti-nuclear Antibody Testing
56. Autoantibodies in Rheumatoid Arthritis
Introduction
Citrullination-Associated Autoantibodies
Antibodies to Post-translational Modifications With Structural Similarity to Citrulline
Antibodies to Malondialdehyde-Acetaldehyde Adducts
Implications of the Anti-modified Protein Antibodies Concept
Other RA Autoantibodies
Conclusion
57. Acute Phase Reactants
Introduction
Acute Phase Response
Acute Phase Reactants in the Management of Rheumatic Diseases
Practical Use of Acute Phase Reactants
C-Reactive Protein and Health: Associations With Nonrheumatologic Conditions
58. Imaging in Rheumatic Diseases
Introduction
Radiography
Computed Tomography
Magnetic Resonance Imaging
Conclusion
Volume II
Part 8. Pharmacology of Anti-rheumatic Drugs
59. Therapeutic Targeting of Prostanoids
Introduction
History
Mechanism of Action
Pharmacology and Dosing
Therapeutic Effects
Adverse Effects
Effects of Concomitant Drugs, Diseases, and Aging
Choosing Anti-inflammatory Analgesic Therapy
Conclusion
60. Glucocorticoid Therapy
Introduction
Structure and Classification of Steroid Hormones
Release of Endogenous Glucocorticoids
Glucocorticoid Mechanisms of Action
Pharmacology of Glucocorticoids
Glucocorticoid Use in the Treatment of Autoimmune Rheumatic Diseases
Adverse Effects of Glucocorticoids
Glucocorticoid Use in Pregnancy and Lactation
Adrenal Insufficiency
“Stress-Dose” Glucocorticoids
Conclusion
61. Traditional DMARDs: Methotrexate, Leflunomide, Sulfasalazine, Hydroxychloroquine, and Combination Therapies
Methotrexate
Leflunomide
Sulfasalazine
Anti-malarials
Combination DMARD Therapy in Rheumatoid Arthritis
62. Immunosuppressive Drugs
Introduction
Cyclophosphamide
Azathioprine
Mycophenolate Mofetil
Cyclosporine, Voclosporin, and Tacrolimus
Conclusion
63. Anti-cytokine Biologics
Introduction
Tumor Necrosis Factor
Interleukin-1
Interleukin-6
Interleukin-17
Interleukin-12/23
Novel Cytokine Inhibition
Biosimilars
JAK–STAT Pathway
Monitoring
Pregnancy and Breastfeeding
Vaccinations
Conclusion
64. Cell-Targeted Biologics and Emerging Targets: Rituximab, Abatacept, and Other Biologics
Introduction
Targeting B Cells
Checkpoint Modulation
Conclusion
65. Janus Kinase and Other Intra-cellular Targets
Introduction
Signal Transduction Pathways
Janus Kinase Inhibitors
JAK Inhibitors for Other Rheumatic Diseases
Conclusion
66. Urate-Lowering Therapy
Introduction
Nonpharmacologic Treatment in Hyperuricemia
Xanthine Oxidase Inhibition
Febuxostat
Uricosurics
Uricases
Urate-Lowering Drugs in Development
67. Bisphosphonates
Introduction
Clinical Pharmacology
Chemistry of Bisphosphonates
Pharmacokinetics
Molecular Mechanism of Action
Treatment Effects and Indications
Adverse Effects and Tolerability
68. Analgesic Agents in Rheumatic Disease
Introduction
Physiology of Pain Perception (the Pain Experience)
Pain Classification
Pharmacologic Treatment of Chronic Pain
Opioids
Anti-depresssants
Anti-convulsants
Muscle Relaxants
Emerging Targets
69. Nutrition and Rheumatic Diseases
Introduction
Challenges in Studying Dietary Effects
Weight Loss
What Do We Know About Exclusion Diet in Inflammatory Arthritis?
What Do We Know About Mediterranean Dietary Pattern and Omega-3 Fatty Acids?
Specific Dietary Supplements
How to Deal With Diet in Patients With Inflammatory Arthritis: Practical Aspects
Diet and Other Types of Arthritis
Conclusion
Part 9. Rheumatoid Arthritis and Sjögren’s Syndrome
70. Etiology of Rheumatoid Arthritis
Introduction
How Rheumatoid Arthritis Begins
Genetic and Environmental Risk
Autoimmunity and Innate Immunity
Infectious Agents and the Microbiome
Microbiome
Changing Epidemiology
71. Pathogenesis of Rheumatoid Arthritis
Introduction
Synovial Features, Cell Types, and Biology
Synovial Fluid and the Synovial Fluid Cartilage Interface
Peripheral Blood Lymphocytes
Role of T Cell Cytokines
Macrophage and Fibroblast Cytokines
Signal Transduction and Transcription Factors
Cell Survival and Death in Rheumatoid Synovium
Synovial Vasculature
Cartilage and Bone Destruction
Conclusion
72. Clinical Features of Rheumatoid Arthritis
Epidemiology and Disease Burden
Pre-rheumatoid Arthritis
Clinical Presentations of Early Rheumatoid Arthritis
Course and Complications of Established Rheumatoid Arthritis
73. Treatment of Rheumatoid Arthritis
Introduction
Goal of Rheumatoid Arthritis Treatment
Classes of Medications
Treatment Approaches and Strategies
Managing Patients “At Target” Who Are Taking Disease-Modifying Anti-rheumatic Drugs
Prevention Trials: A Step in the Right Direction
Interpreting Radiographic Progression and the Use of Other Imaging Modalities
Adjuncts to Medications
Comorbidities and the Interactions of Rheumatologists With Primary Care Physicians
Perioperative Management of Rheumatoid Arthritis Medications
Patients With Rheumatoid Arthritis Are Doing Better
Conclusion
74. Sjögren’s Syndrome
Historical Perspective
Definitions and Classification Criteria
Epidemiology
Etiology and Pathogenesis
Clinical Features
Diagnosis and Diagnostic Tests
Treatment
Outcome
Conclusion
Part 10. Spondyloarthritis
75. Classification and Epidemiology of Spondyloarthritis
Introduction
Classification Criteria
Epidemiology of Spondyloarthritis
76. Axial Spondyloarthritis
Introduction
Classification Criteria for Ankylosing Spondylitis and Axial Spondyloarthritis
Epidemiology
Genetics and Pathogenesis
Clinical Manifestations
Imaging
Diagnosis
Prognosis and Outcomes
Monitoring and Management
Conclusion
77. Reactive Arthritis
Introduction and Historical Background
Epidemiology
Etiology and Triggering Organisms
Clinical Features
Laboratory, Radiographic, and Advanced Imaging Findings
Diagnosis
Treatment
Conclusion
78. Psoriatic Arthritis
Introduction
Epidemiology
Clinical Features
Differential Diagnosis
Laboratory Features
Radiographic Features
Diagnosis and Classification Criteria
Clinical Course and Outcome
Comorbidities in Psoriatic Arthritis
Outcome Domains and Instruments
Pathogenesis
Treatment
Conclusion and Future Research Agenda
79. Inflammatory Bowel Disease–Associated Arthritis and Other Enteropathic Arthropathies
Introduction
Inflammatory Bowel Disease–Associated Arthritis
Pathophysiology of Spondyloarthritis and Inflammatory Bowel Disease: From Gut Mucosa and Microbiome to Joint Disease
Clinical Manifestations and Diagnosis of Inflammatory Bowel Disease–Associated Arthritis
Assessment and Monitoring of Disease Activity
Management
Other Enteropathic Arthropathies
Part 11. Systemic Lupus Erythematosus and Related Syndromes
80. Etiology and Pathogenesis of Systemic Lupus Erythematosus
Introduction
Historic View of Systemic Lupus Erythematosus Pathogenesis
Genetic Contributions to Systemic Lupus Erythematosus Pathogenesis
Female Predominance of Systemic Lupus Erythematosus
Environmental Triggers of Systemic Lupus Erythematosus
Innate Immune System Activation in Systemic Lupus Erythematosus
Adaptive Immune System Alterations in Systemic Lupus Erythematosus
Autoantibodies in Systemic Lupus Erythematosus
Mechanisms of Target Organ Damage
Conclusion
81. Clinical Features of Systemic Lupus Erythematosus
Introduction
Epidemiology
Clinical Features
Diagnosis
Differential Diagnosis
Neonatal Lupus
82. Treatment of Systemic Lupus Erythematosus
Clinical Course and General Treatment Strategy
Patient and Physician Preferences
Drugs Used in the Treatment of Systemic Lupus Erythematosus
Management of Specific Systemic Lupus Erythematosus Manifestations and Treatment Algorithms
Special Issues: Treat-to-Target, Refractory Disease and Lupus in Pregnancy
Comorbidities
Evidence and Expert-Based Recommendations in Systemic Lupus Erythematosus
Current Trends and Future Perspectives
83. Antiphospholipid Syndrome
Introduction
Epidemiology
Etiology
Pathogenesis
Clinical Features
Diagnosis
Management
Outcome
Part 12. Systemic Sclerosis, Inflammatory Myopathies, and Overlap Syndromes
84. Etiology and Pathogenesis of Systemic Sclerosis
Introduction
Etiology
Infectious Agents and Viruses
Environmental Exposures, Dietary Factors, Drugs, and Radiation
Microbiome Alterations in Systemic Sclerosis
Microchimerism
Pathology
Organ-Specific Pathologic Findings
Animal Models of Scleroderma
Pathogenesis
Inflammation and Immune Dysregulation in the Pathogenesis of Systemic Sclerosis
Humoral Autoimmunity and B Cells
Fibrosis
Cellular Senescence and Fibrosis in Systemic Sclerosis
Molecular Determinants of Fibrosis: Transforming Growth Factor-β
Cytokines, Growth Factors, Chemokines, and Lipid Mediators
Scleroderma Fibroblast
Conclusion
85. Clinical Features and Treatment of Scleroderma
Epidemiology
Clinical Features
General Principles of Disease Evaluation
General Guidelines for Management
Raynaud’s Phenomenon
Skin Involvement
Interstitial Lung Disease
Pulmonary Hypertension
Renal Involvement
Gastrointestinal Involvement
Primary Cardiac Involvement
Musculoskeletal Involvement
Associated Disorders
Psychosocial Aspects
Conclusion and Practical Recommendations
86. Inflammatory Diseases of Muscle and Other Myopathies
Introduction
Epidemiology
Etiology of Myositis
Pathogenesis
Clinical Features
Classification and Diagnostic Criteria
Clinical Evaluation
Management and Outcome
87. Overlap Syndromes
Introduction
Historical Background
Immunogenetics of Overlap Syndromes
Autoantibodies in Overlap Syndromes
Mixed Connective Tissue Disease
Patients Presenting With Undifferentiated Rheumatic Disease
Overlap Syndromes With Dominant Features of Scleroderma
Overlap Syndromes With Dominant Features of Myositis
Sjögren’s Syndrome and Autoimmune Thyroid Disease
Treatment of Overlap Connective Tisue Disease Syndromes
Part 13. Vasculitis
88. Classification and Epidemiology of Systemic Vasculitis
Introduction
Classification of Vasculitis
Epidemiology of Vasculitis
89. Giant Cell Arteritis, Polymyalgia Rheumatica, and Takayasu’s Arteritis
Introduction
Giant Cell Arteritis and Polymyalgia Rheumatica
Takayasu’s Arteritis
90. Anti-neutrophil Cytoplasmic Antibody–Associated Vasculitis
Introduction
Classification Criteria and Nomenclature
Epidemiology
Genetics
Clinical Manifestations
Diagnostic Testing
Treatment
Outcomes
Pathogenesis
Conclusion
91. Polyarteritis Nodosa
Definition and Classification
Epidemiology
Etiology and Pathogenesis
Clinical Features and Diagnostic Tests
Differential Diagnosis
Treatment
Outcome
Cutaneous Polyarteritis Nodosa
Monogenic Mimic of Polyarteritis Nodosa: Deficiency of Adenosine Deaminase 2
92. Immune Complex–Mediated Small Vessel Vasculitis
Introduction
Pathogenesis
Cutaneous Manifestations
Pathology
Differential Diagnosis
Clinical Syndromes
93. Primary Central Nervous System Vasculitis
Introduction
Epidemiology
Genetics
Clinical Features
CNSV Subsets
Diagnosis and Diagnostic Tests
Differential Diagnosis
Treatment
Outcome
Conclusion
94. Behçet’s Disease
Introduction
Epidemiology
Pathogenesis
Clinical Features
Diagnosis
Treatment
Prognosis
Part 14. Crystal-Induced and Inflammasome-Mediated Inflammation
95. Pathogenesis of Inflammasome-Mediated Diseases
Introduction
Inflammasome Biology
Functional Inflammasomes
Other Inflammasomes
Inflammasomes in Autoimmunity
Inflammasome-Targeted Therapies
Conclusion
96. Etiology and Pathogenesis of Hyperuricemia and Gout
Introduction
Evolutionary Considerations
Determinants of Urate Levels
Asymptomatic Hyperuricemia and the Biological Effects of Soluble Urate
Crystal Formation: The Transition From Hyperuricemia to Gout
Acute Gout Flares: The Inflammatory Response to MSU Crystals
Chronic Gouty Arthritis and Tophaceous Gout
Gout and Comorbidities
97. Clinical Features and Treatment of Gout
Classification Criteria
Clinical Features of Gout
Gout Management
Comorbidity Assessment and Management in Patients With Gout
Outcome
Strategies to Improve Gout Care
98. Calcium Crystal Disease: Calcium Pyrophosphate Deposition Disease and Basic Calcium Phosphate-Associated Syndromes
Introduction
Calcium Pyrophosphate Deposition Disease
Basic Calcium Phosphate–Associated Arthritis
99. Familial and Nonfamilial Autoinflammatory Syndromes
Introduction
Inflammasomopathies and IL-1-Driven Autoinflammatory Diseases
Interferonopathies
NF-κB-Related and/or Aberrant TNF Activity Autoinflammatory Syndromes
Ubiquitination Defects
Other Autoinflammatory Diseases
Diagnostic Approach to Autoinflammatory Diseases
Treatment of Autoinflammatory Diseases
Conclusion
Part 15. Cartilage, Bone, and Heritable Connective Tissue Disorders
100. Etiology and Pathogenesis of Osteoarthritis
Introduction
The Synovial Joint Is an Organ
Endogenous Joint Tissue Repair Processes
Osteoarthritis Risk Factors and Their Effects on Joint Physiology
Pain Experiences and Nociceptive Signaling in OA
Joint Tissue Damage
Conclusion
101. Clinical Features of Osteoarthritis
Introduction
Epidemiology of Osteoarthritis
Phenotypes in OA
Clinical Features
Diagnostic Tests
Outcome
Conclusion
102. Treatment of Osteoarthritis
Introduction
Therapeutic Pain Targets in Osteoarthritis
Approach to Management of Osteoarthritis
Experimental Osteoarthritis Therapies Under Development
103. Metabolic Bone Disease
Introduction
Osteoporosis
Treatment
Glucocorticoid-Induced Osteoporosis
Osteomalacia
Hypophosphatasia
Paget’s Disease of Bone
Osteoporosis Induced by Other Medications
104. Proliferative Bone Diseases
Introduction
Diffuse Idiopathic Skeletal Hyperostosis
Hypertrophic Osteoarthropathy
SAPHO Syndrome
105. Osteonecrosis
Introduction
Epidemiology
Etiology
Clinical Variants
Staging Osteonecrosis
Pathogenesis
Genetic and Epigenetic Regulation in Osteonecrosis
Diagnosis
The Natural History of Osteonecrosis
Treatment of Osteonecrosis
Conclusion
106. Relapsing Polychondritis
Introduction
Epidemiology
Pathology
Pathogenesis
Clinical Features
Associated Disorders
Differential Diagnosis
Diagnostic Tests
Treatment
Outcome
Conclusion
107. Heritable Diseases of Connective Tissues
Introduction
Skeletal Dysplasias: Overview
Specific Heritable Disorders of Connective Tissue
Conclusion
Part 16. Rheumatic Diseases of Childhood
108. Etiology and Pathogenesis of Juvenile Idiopathic Arthritis
Introduction
Epidemiology
Histopathology
JIA Pathogenesis
Subtype-Specific Pathogenesis
Conclusion
109. Clinical Features and Treatment of Juvenile Idiopathic Arthritis
Introduction
Classification Criteria for Juvenile Idiopathic Arthritis and Differential Diagnosis
Oligoarticular Juvenile Idiopathic Arthritis
Rheumatoid Factor–Negative Polyarticular Juvenile Idiopathic Arthritis
Rheumatoid Factor–Positive Polyarticular Juvenile Idiopathic Arthritis
Juvenile Spondyloarthritis and Enthesitis-Related Arthritis
Juvenile Psoriatic Arthritis
Systemic Juvenile Idiopathic Arthritis
Treatment—Medical Therapy
Treatment of Juvenile Idiopathic Arthritis Subtypes
Clinical Features and Management of Juvenile Idiopathic Arthritis–Associated Uveitis
Imaging
Outcomes
Special Considerations in Children
Conclusion
110. Childhood-Onset Systemic Lupus Erythematosus, Drug-Induced Lupus in Children, and Neonatal Lupus
Childhood-Onset Systemic Lupus Erythematosus
Drug-Induced Lupus
Neonatal Lupus
Conclusion
111. Juvenile Dermatomyositis, Scleroderma, and Vasculitis
Juvenile Dermatomyositis
Pediatric Scleroderma: Systemic and Localized Forms
Pediatric Vasculitis
Part 17. Infections and Rheumatic Disease
112. Bacterial Arthritis
Epidemiology
Nongonococcal Arthritis
Prosthetic Joint Infections
Conclusion
113. Lyme Disease
Introduction
Ecology and Epidemiology of Lyme Disease
Ticks and Lyme Disease
Pathogenesis
Clinical Features of Lyme Disease
Lyme Arthritis and Other Musculoskeletal Manifestations of Lyme Disease
Diagnosis
Treatment
Special Considerations
Outcomes
Post-treatment Lyme Disease Syndrome
Prevention
Conclusion
114. Mycobacterial Infections of Bones and Joints
Introduction
Clinical Scenarios
Diagnosis
Treatment
Osteoarticular Infections Caused by Nontuberculous Mycobacteria
Emergence of Nontuberculous Mycobacterial Infections During the Treatment of Rheumatic Diseases
115. Fungal Infections of Bones and Joints
Introduction
Coccidioidomycosis
Blastomycosis
Cryptococcosis
Candidiasis
Sporotrichosis
Aspergillosis
Histoplasmosis
Scedosporiosis
Treatment of Fungal Infection
Fungal Infection as a Consequence of Anti-rheumatic Therapy
116. Rheumatic Manifestations of Human Immunodeficiency Virus Infection
Introduction
HIV-Associated Bone and Joint Disease
HIV-Associated Muscle Disease
Diffuse Infiltrative Lymphocytosis Syndrome
Vasculitis Associated With HIV Infection
Thrombotic Thrombocytopenic Purpura
Primary Pulmonary Hypertension
HIV-Associated Musculoskeletal Infection
Response of Other Rheumatic Diseases to HIV Infection
HAART-Related Immune Reconstitution Syndrome
Laboratory Abnormalities Associated With HIV Infection
Conclusion
117. Viral Arthritis
Introduction
Examples of Arthritogenic Viruses
Arthritogenic Viruses Hijack the Innate Interferon Type I Response to Favor Persistence
Arthritogenic Viruses Engage Trojan Horse Scenario to Avoid Adaptive Immunity
Other Mechanisms Favoring Viral Persistence Inside Synovial Tissues
Mechanisms Involved in Chronic Arthralgias
Mechanisms Involved in Chronic Inflammatory Viral Arthritis Resembling Rheumatoid Arthritis
Treatment and Prevention
Conclusion
118. Rheumatic Fever and Post-streptococcal Arthritis
Introduction
Rheumatic Fever and Rheumatic Heart Disease
Post-streptococcal Arthritis
Conclusion
119. COVID-19 and Rheumatic Disease
Introduction
Risk of SARS-CoV-2 Infection
Impact of Immunosuppression on COVID-19 Outcomes
Multisystem Inflammatory Syndrome in Children and Adults
Autoantibodies and De Novo Autoimmune Disease in COVID-19
Strategies to Mitigate Poor COVID-19 Outcomes in Immunosuppressed Patients With Rheumatic Disease
Conclusion
120. Vaccination in Rheumatic Disease
Introduction
Influenza Vaccine
Pneumococcal Vaccination
Herpes Zoster Vaccination
SARS-CoV-2 Vaccination
Hepatitis B Vaccination
Human Papilloma Virus Vaccination
Tetanus Vaccination
Yellow Fever Vaccination
Conclusions
Part 18. Arthritis Accompanying Systemic Disease
121. Amyloidosis
Introduction
Diagnosis of Amyloidosis
AA Amyloidosis
Epidemiology of AA Amyloidosis
Genetics of AA Amyloidosis
Clinical Features of AA Amyloidosis
Other Important Types of Systemic Amyloidosis
Diagnostic Tests for AA Amyloidosis
Treatment of AA Amyloidosis
Outcomes
Conclusion
122. Sarcoidosis
Introduction
Classification Criteria
Epidemiology
Etiology
Genetics
Pathogenesis
Clinical Features
Diagnosis and Diagnostic Tests
Treatment
Outcome and Prognosis
Conclusion
123. Hemochromatosis
Introduction
Iron Metabolism in Health and Disease
Genetics
Epidemiology
Influence of Other Genes and Environment
Pathogenesis
Clinical Features
Differential Diagnosis
Diagnostic Tests
Screening
Treatment
Outcomes
Conclusion
124. Hemophilic Arthropathy
Introduction
Clinical Features
Diagnosis
Pathogenesis
Treatment of Hemophilia
Conclusion
125. Rheumatic Manifestations of Hemoglobinopathies
Introduction
Thalassemia
Sickle Cell Anemia and Related Disorders
Musculoskeletal Involvement: Sickle Cell Disease
Musculoskeletal Involvement: Thalassemia
Iron Metabolism
Comorbid Rheumatic Disease
Conclusion
126. IgG4-Related Disease
Introduction
Epidemiology
Classification Criteria
Pathology Features
Serum IgG4 Concentrations
Pathophysiology
B Cell Lineage
T Cells
T Follicular Helper Cells
CD4+ Cytotoxic T Lymphocytes
Clinical Manifestations
Proliferative Versus Fibrotic Subsets of Disease Manifestations
Differential Diagnosis
Treatment
127. Arthritis Accompanying Endocrine and Metabolic Disorders
Introduction
Adrenal Gland Disorders
Acromegaly
Hypothalamic–Gonadal Axis
Diabetes Mellitus
Bone Mineral Disease
Thyroid Disease
Hypothyroidism
Parathyroid Disease
Hyperparathyroidism
Lipid Disorders
128. Rheumatic Paraneoplastic Syndromes and Malignancies With Rheumatic Manifestations
Introduction
Paraneoplastic Arthritis
Palmar Fasciitis and Polyarthritis Syndrome
Remitting Seronegative Symmetric Synovitis With Pitting Edema
Pancreatic Panniculitis and Polyarthritis
Erythromelalgia
Paraneoplastic Vasculitis
Hypertrophic (Pulmonary) Osteoarthropathy
Eosinophilic Fasciitis
Tumor-Induced Osteomalacia
Cancer-Associated Myositis and Scleroderma
Malignancies With Musculoskeletal Manifestations
Cancer Treatments and Rheumatic Manifestations
Conclusion
129. Tumors and Tumor-like Lesions of Joints and Related Structures
Introduction
Non-neoplastic Lesions
Neoplasms
Malignant Tumors of the Joint
Primary Sarcomas of Joints
Secondary Malignant Tumors of the Joint
130. Autoimmune Complications of Immune Checkpoint Inhibitors for Cancer
Introduction
Immune-Related Adverse Events
Rheumatologic Immune-Related Adverse Events
Treatment of Rheumatologic Immune-Related Adverse Events
Pre-existing Autoimmune Disease and Immune Checkpoint Inhibitor Use
Index
Chapter Acknowledgments
Chapter Acknowledgments

Gary S. Firestein

Gary Firestein, MD, is a board-certified rheumatologist who diagnoses and treats patients with autoimmune conditions as well as diseases of the joints, muscles and bones. A professor at UC San Diego School of Medicine, Dr. Firestein is distinguished for his research and serves as director of the Altman Clinical and Translational Research Institute and the senior associate vice chancellor for health sciences. Dr. Firestein's research interest focuses on the pathogenesis and treatment of rheumatoid arthritis. Dr. Firestein is the recipient of many awards and honors, including the Arthritis Foundation's Jane Wyman Humanitarian Award in 2010 for his contributions to rheumatology; the Arthritis Foundation Lee C. Howley Sr. Prize for Arthritis Research; and the American College of Rheumatology Distinguished Investigator Award. He has been elected to the American Society for Clinical Investigation and the Association of American Physicians. He has served as an editor for the Textbook of Rheumatology for since the 7th edition (2004).

Affiliations and expertise

Distinguished Professor of Medicine, Senior Associate Vice Chancellor for Health Sciences, Director, Altman Clinical and Translational Research Institute, USA

Iain B. McInnes

Iain McInnes is Director of the Institute of Infection, Immunity and Inflammation at the University of Glasgow, UK. He has extensive experience in leading multicenter programs nationally and internationally. He is Director of the Scottish MRC Clinical Pharmacology and Pathology Clinical PhD Training Program, Chief Investigator for the Scottish Early RA Cohort (SERA) and the related SMS-IC biomarker discovery program (PROMISERA), and chief investigator of numerous global phase II and III clinical trials of novel immune therapies. He has served as member or chair of numerous national grant-funding panels and as chair of several European League Against Rheumatism (EULAR) scientific committees – he is now Treasurer and President Elect of EULAR serving on its Steering Committee. He is formerly Chairman of the Foundation for European Rheumatology Research (Foreum) Scientific Committee and leads the EULAR-supported European Roadmap Program that is defining the research agenda for rheumatology for the next decade.

Affiliations and expertise

Muirhead Professor of Medicine, Arthritis Research UK Professor of Rheumatology, Director of Institute of Infection,Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom

Gary Koretzky

Gary Koretzky, MD, PhD is Professor of Medicine at Weill Cornell Graduate School. Dr. Koretzky’s research aims to better understand the signal transduction events that occur following engagement of the T cell antigen receptor. He has been continuously funded by the National Institutes of Health since establishing his independent research group, as the laboratory has expanded its interests to study more globally the molecular events important for immune cell development, differentiation and function. Dr. Koretzky has published more than 200 research articles. He is a past President of the American Society of Clinical Investigation (2000) and Councilor of the Association of American Physicians (2008-2012), is a Fellow of the American Association for the Advancement of Science (2004), a member of the Institute of Medicine of the National Academies (2008), a Fellow of the American Academy of Arts & Sciences (2012) and serves as the Editor-in-Chief of Immunological Reviews (2002-present).

Affiliations and expertise

Vice Dean at Weill Cornell Medical College, Frank H.T. Rhodes Distinguished Professor of Cardiovascular Biology and Genetics, USA

Ted Mikuls

Dr. Mikuls is a rheumatologist and epidemiologist with research interests focused on the epidemiology, pathogenesis, and outcomes of rheumatoid arthritis (RA) and gout. He is actively engaged in clinical/translational research activities and has received research funding from the NIH, U.S. Department of Defense, Veterans Affairs, the Rheumatology Research Foundation, and industry. He has extensive experience conducting multi-center / multidisciplinary trials, serving as the Principal Investigator (PI) for the multicenter Veterans Affairs Rheumatoid Arthritis (VARA) registry since its inception in 2003. He has served on multiple national study sections including those convened by the NIH, VA, and the Rheumatology Research Foundation. He previously chaired the American College of Rheumatology (ACR) Subcommittee for Practice Guidelines, served on the US FDA’s Arthritis Advisory Committee, and was the Lead Editor for the textbook A Color Handbook – Rheumatology.

Affiliations and expertise

Stokes Shackleford Professor and Vice-Chair for Research, Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, USA

Tuhina Neogi

Tuhina Neogi is a rheumatologist and epidemiologist whose research has focused primarily on risk factors for knee osteoarthritis and gout, pain mechanisms in knee osteoarthritis, as well as methodologic issues of relevance for rheumatic diseases. Dr. Neogi has had continuous peer-reviewed foundation and NIH funding since 2003 and has over 250 peer-reviewed publications to date. She is a past chair of the FDA Arthritis Advisory Committee, serve(d) on the boards of two international societies: Osteoarthritis Research Society International (OARSI) and Gout, Hyperuricemia, and Crystal-Associated Diseases Network (G-CAN), and on committees for the American College of Rheumatology (ACR) and International Association for the Study Pain (IASP), among others. Her work has been recognized with the prestigious 2014 ACR Henry Kunkel Young Investigator Award for outstanding and promising independent contributions to rheumatology research and she has also engaged in developing new classification criteria for a number of rheumatic diseases.

Affiliations and expertise

Section Chief of Rheumatology, Rheumatology, Professor, Rheumatology, Boston University School of Medicine, USA

James R. O'Dell

James R. O’Dell, MD is the Stokes Shackleford Professor of Internal Medicine, Vice-Chairman of Internal Medicine and Chief of the Division of Rheumatology at the University of Nebraska Medical Center (UNMC) in Omaha. Dr. O’Dell founded and has directed the Rheumatoid Arthritis Investigational Network (RAIN) for the last 25 years. Dr. O’Dell is the PI of the large multinational RA research study based at the VA through their cooperative studies program. Dr. O’Dell has published extensively, mostly in the area of rheumatoid arthritis. He has presented frequently at national and international meetings and has more than 100 published articles in top-level rheumatology journals. He has served on numerous American College of Rheumatology (ACR) committees over the last 20 years, including time on both the ACR and REF BOD, as well as a two-year term as President of the Research and Education Foundation of the ACR and was President of the College (2011-2012). Additionally, he is Editor-in-Chief of Up To Date for Rheumatology.

Affiliations and expertise

Bruce Professor and Vice Chairman of Internal Medicine, University of Nebraska Medical Center, Chief of Rheumatology, Department of Medicine, Omaha Veterans Affairs, Omaha, Nebraska, USA

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Gary S. Firestein

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James R. O'Dell

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