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

11th Edition - July 5, 2020
Imprint: Elsevier
Authors: Gary S. Firestein, Ralph C. Budd, Sherine E Gabriel, Iain B. McInnes, James R. O'Dell
Editor: Gary Koretzky
Language: English
Hardback ISBN:
9 7 8 - 0 - 3 2 3 - 6 3 9 2 0 - 0
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 6 3 9 2 1 - 7

Through 10 outstanding editions, Kelley & Firestein’s Textbook of Rheumatology has provided authoritative, in-depth guidance in rheumatology with an ideal balance of basic sci… Read more

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

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Through 10 outstanding editions, Kelley & Firestein’s Textbook of Rheumatology has provided authoritative, in-depth guidance in rheumatology with an ideal balance of basic science and clinical application. The 11th Edition of this classic text continues this tradition of excellence, while keeping you abreast of recent advances in genetics and the microbiome, new therapies such as biologics and biosimilars, and other rapid changes in the field. It provides comprehensive, global coverage of all aspects of diagnosis, screening, and treatment in both adults and children, in a user-friendly, full color reference.

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. Biology of the Normal Joint
Classification of Joints
Developmental Biology of the Diarthrodial Joint
Interzone Formation and Joint Cavitation
Cartilage Formation and Endochondral Ossification
Development of Articular Cartilage
Development of the Joint Capsule, Synovial Lining, Menisci, and Intracapsular Ligaments
Development of Nonarticular Joints
Organization and Physiology of the Mature Joint
Synovium
Joint Innervation
Synovial Fluid and Nutrition of Joint Structures
Generation and Clearance of Synovial Fluid
Synovial Fluid as an Indicator of Joint Function
Lubrication and Nutrition of the Articular Cartilage
Mature Articular Cartilage
Subchondral Bone
Tendons
Ligaments
Bursae
Menisci
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. Biology, Physiology, and Morphology of Bone
Structure and Composition of Bone
Conclusion
5. Muscle: Anatomy, Physiology, and Biochemistry
Introduction
Structure
Events During Muscle Contraction
Transmission of Force to the Exterior
Energetics
Fatigue and Recovery
Plasticity
Aging
Conclusion
6. Biomechanics
Introduction
Kinematics
Kinetics
Joint Biomechanics
Joint Constraint and Stability
Mechanical Loading on Tendon
7. Regenerative Medicine and Tissue Engineering
Introduction
Intrinsic Repair
Emerging Clinical Applications Targeting Endogenous Repair
Extrinsic Repair: Current Therapeutic Interventions
Regenerative Medicine and Tissue Engineering in Arthritis
Conclusion
8. Proteinases and Matrix Degradation
Introduction
Extra-cellular Matrix-Degrading Proteinases
Regulation of Proteinase Activity
Inhibition of Proteinases by Endogenous Inhibitors
Part 2. Cells Involved in Autoimmune Diseases and Inflammation
9. Dendritic Cells
Introduction
Dendritic Cell Subsets and Development
New Developments in Dendritic Cell Classification
Impairment of Dendritic Cell Biology in Disease
Immunotherapeutic Strategies and Clinical Trials
Future Directions
10. Mononuclear Phagocytes
Introduction
Steady-State Development of Synovial Macrophages
Transcriptional Regulation of Synovial Macrophages
Synovial Macrophage Production of Cytokines and Chemokines
Conclusion
11. Neutrophils
Overview
Neutrophil Development, Morphology, and Content
Neutrophil Activation and Signal Transduction
Neutrophil Function
Heritable Disorders of Neutrophil Function
Neutrophil Relevance to Rheumatic Disease
Conclusion
12. T Lymphocytes
Introduction
T Cell Development
Peripheral Migration and Homeostatic Proliferation of T Cells
T Cell Subsets
Future Directions
13. B Cells
Introduction
Immunoglobulins: Structure and Function
B Cell Development
Sites of B Cell Homing and Activation
B Cell Activation and Differentiation
Repertoire Selection
B Cell–Mediated Autoimmunity
Conclusion
14. Fibroblasts and Fibroblast-like Synoviocytes
What Is a Fibroblast?
Physiologic Characteristics and Functions of Fibroblasts
Fibroblasts in Rheumatic Diseases
Fibroblast-like Synoviocytes in Rheumatoid Arthritis
Conclusion
15. Mast Cells
Introduction
Basic Biology of Mast Cells
Role of Mast Cells in Health and Disease
Conclusions
16. Innate Lymphoid Cells and Natural Killer Cells
Introduction
Biology of ILCs and NK Cells
ILCs and Potential Contributions to Rheumatologic Disease
Summary
17. Platelets and Megakaryocytes
Introduction
Platelet Structure
Platelet Production
Platelets and Hemostasis
Signaling Pathways in Platelet Activation
The Platelet as an Inflammatory Cell
The Megakaryocyte as an Inflammatory 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
Innate Receptor Signaling
Intra-cellular Receptor Signaling
Adaptor Molecules
Signaling Pathways
Transcription Factors
Conclusion
19. The Immunologic Repercussions of Cell Death
Introduction
Types of Cell Death
Molecular Mechanisms of Caspase Activation
Molecular Pathways of Regulated Necrosis
Cell Death and Immunity
Conclusion and Clinical Potential
20. 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
Cell Types Mediating Innate Immunity
Influence of Innate Mechanisms on Adaptive Immunity
Disease Associations Involving Innate Immunity
Future Directions
Connection to the Clinic
21. 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
22. Autoimmunity and Tolerance
Introduction
Definition and Classification of Pathogenic Autoimmunity
Animal Models of Autoimmunity
Tolerance Mechanisms
Theories of Autoimmunity
Immunologic Mechanisms of Tissue Inflammation and Dysfunction
Pathophysiology of Autoimmune Rheumatic Diseases
Genetics of Autoimmune Diseases
Sex and Autoimmunity
Microbial and Other Environmental Triggers
Conclusion
23. The Microbiome in Health and Disease
The Human Microbiome
What Is the Microbiome?
Principles of Host-Microbiome Interaction
What Affects the Microbiome?
How Is the Microbiome Determined From a Sample?
How Are Microbiome Data Interpreted?
What Can the Microbiome Be Used for Today?
What Microbiome Principles From Other Areas of Medicine or Biology Can Be Applied to Rheumatology?
How Will the Microbiome Be Useful to Rheumatologists in the Future?
24. Metabolic Regulation of Immunity
Introduction
Metabolic Rewiring in Innate Immunity
Metabolic Rewiring in Adaptive Immunity
Mitochondria and Immunity
Metabolic Interplay in the Immune Microenvironment
Conclusion
25. Genetics of Rheumatic Diseases
Introduction
Evidence for a Genetic Component to Rheumatic Diseases
Study Design
Identification of High-Risk Groups
26. Epigenetics of Rheumatic Diseases
Introduction
Epigenetic Regulation
Epigenetics and the Immune Response
Challenges Faced in Translational Epigenetics Research
Epigenetics in Rheumatic Diseases
Epigenetic Modifications as Biomarkers of Rheumatic Disease
Future Directions
27. Complement System
Introduction
Functions of the Complement System
Terminology Used 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
28. 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
29. Chemokines and Cellular Recruitment
Introduction
Defining Membership of the Chemokine Family
The Chemokine Nomenclature System
The Inflammatory and Homeostatic Chemokine Model
The Chemokine Receptor Family
Atypical Chemokine Receptors
Chemokines in an Evolutionary Context
How Chemokines Attract Cells to Particular In Vivo Destinations
Chemokines and Their Receptors in Disease
Conclusion
30. Angiogenesis
Introduction
Endothelial Cells
31. Cytokines
Introduction
Classification of Cytokines
Assessing Cytokine Function In Vitro and In Vivo
Cytokine Receptors
Regulation of Cytokine Expression
Effector Function of Cytokines
Cytokine Effects Beyond Immune Regulation
Conclusion
32. Experimental Models for Rheumatoid Arthritis
Introduction
Arthritis Caused by Infectious Agents
Arthritis Caused by Bacterial Fragments
Adjuvant-Induced Arthritis
Cartilage Protein-Induced Arthritis
Spontaneous Arthritis
Use of Animal Models
Ethical Considerations
Conclusion
33. Neuronal Regulation of Pain and Inflammation
Introduction
Primary Afferent Fibers
Efferent Functions of Primary Afferent Fibers
Neuronal Regulation of Inflammation in Acute Inflammatory Models
Neuronal Regulation of Inflammation in Chronic Models of Inflammation
Sympathetic Effects on Peripheral Inflammation Are Time Dependent
Parasympathetic Effects on Peripheral Inflammation
Role of Pain in Inflammatory Disease
Part 4. Broad Issues in the Approach to Rheumatic Disease
34. Clinical Research Methods in Rheumatic Disease
Introduction
Measures of Disease Occurrence
Measures of Effect
Data Sources for Research in Rheumatology
Clinical Research Study Designs
Biases in Study Design
Effect Measure Modification
Screening
Conclusion
35. Economic Impact of Arthritis and Rheumatic Conditions
Introduction
Cost-of-Illness Studies of Arthritis and the Rheumatic Conditions
Summary
36. Assessment of Health Outcomes
Introduction
Health Outcome Assessments
What Needs to Be Measured: Defining Measurement Needs
Outcome Measures in Arthritis
Deciding on an Instrument for a Health Outcome Assessment
Examples of Arthritis Instruments
Areas of Growth in Health Outcome Assessment
Conclusion
37. 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
38. Occupational and Recreational Musculoskeletal Disorders
Introduction
Occupation-Related Musculoskeletal Disorders
Occupation-Related Rheumatic Diseases
Recreation- and Sports-Related Musculoskeletal Disorders
Performing Arts–Related Musculoskeletal Disorders
39. 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
40. Cancer Risk in Rheumatic Diseases
Introduction
Malignancy in Autoimmune Rheumatic Diseases
Rheumatoid Arthritis
Systemic Lupus Erythematosus
Systemic Sclerosis (Scleroderma)
Idiopathic Inflammatory Myopathy
Sjögren Syndrome
Vasculitis
Seronegative Spondyloarthritis
Cancer Risks Associated With Anti-rheumatic Drug Therapies
Nonbiologic DMARD Therapy
Biologic Response Modifiers
Cancer Screening in Patients With Rheumatic Disease
Conclusion
41. Introduction to Physical Medicine and Rehabilitation
Introduction
Rehabilitation Interventions
Specific Disorders
Alternative, Innovative, and Emerging Therapeutic Approaches
Conclusion
42. Pregnancy and Rheumatic Diseases
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 Antibody
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
43. History and Physical Examination of the Musculoskeletal System
History in a Patient With Musculoskeletal Disease
Systematic Method of Examination
Recording the Joint Examination
Interpreting the Joint Examination
Examination of Specific Joints
44. Ultrasound in Rheumatology
Introduction
Technical Aspects
Artifacts
Examination Technique
Ultrasound in Rheumatology Definitions
Rheumatoid Arthritis
Osteoarthritis
Crystalline Arthropathy
Gout
Calcium Pyrophosphate Dihydrate Crystal Deposition
Spondyloarthropathy
Polymyalgia Rheumatica
Giant Cell Arteritis
Sjögren’s Syndrome
Sclerosing Diseases
Non-inflammatory Conditions
Pediatric Rheumatology
Ultrasound in Rheumatology Intervention
Conclusion
45. Evaluation of Monoarticular and Polyarticular Arthritis
Introduction
Approach to the Patient With Arthritis
Synovial or Bone Biopsy
Differential Diagnosis
Formal Criteria and Their Role in Clinical Diagnosis
Preliminary Diagnoses, Working Diagnoses, Presumptive Treatments, Reassessments, and Future Perspectives
46. Skin and Rheumatic Diseases
Diagnosis of Skin Lesions Associated With Rheumatic Diseases
Psoriasis
Reactive Arthritis
Rheumatoid Arthritis
Juvenile Rheumatoid Arthritis/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
47. 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
48. Neck Pain
Epidemiology
Anatomy
Axial Neck Pain
Radiculopathy and Myelopathy
Clinical Features
Diagnostic Evaluation
Differential Diagnosis and Treatment
49. Shoulder Pain
Introduction
Anatomy and Function
Diagnosis
Intrinsic Factors Causing Shoulder Pain
Extrinsic or Regional Factors Causing Shoulder Pain
50. Low Back Pain
Epidemiology
Anatomy
Clinical Evaluation
Differential Diagnosis
Spondylolisthesis
Spinal Stenosis
Diffuse Idiopathic Skeletal Hyperostosis
Treatment
Outcome
Conclusion
51. Hip and Knee Pain
Introduction
Knee Pain
Hip Pain
52. Foot and Ankle Pain
Introduction
Functional Anatomy and Biomechanics
Diagnostic Evaluation
Imaging
Differential Diagnosis of Ankle Pain
Differential Diagnosis of Foot Pain
Nonoperative Treatment
Operative Treatment
Conclusion
53. Hand and Wrist Pain
Introduction
Patient Evaluation
Physical Examination
Common Causes of Hand and Wrist Pain
54. Temporomandibular Joint Pain
Introduction
Arthritis of the Temporomandibular Joint
Internal Derangements
Neoplasms
Myofascial Pain and Dysfunction
Conclusion
55. 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
56. Synovial Fluid Analyses, Synovial Biopsy, and Synovial Pathology
Introduction
Synovial Fluid Analysis
Biochemical Analysis of Synovial Fluid
Synovial Biopsy
Synovial Pathology
Synovial Immunohistology
Conclusion
57. 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 Limbs Injections
Soft Tissue Injections: Upper Limbs
Soft Tissue Injections: Lower Limbs
Conclusion
58. Anti-nuclear Antibodies
Introduction
History
Relevance of Anti-nuclear Antibodies to Disease Pathogenesis
Methods of Detection
Interpretation of the FANA
Diseases Associated With Anti-nuclear Antibodies
Clinical Utility of Anti-nuclear Antibody Testing
59. Autoantibodies in Rheumatoid Arthritis
Introduction
Citrullination-Associated Autoantibodies
Antibodies to Citrullinated Proteins
Anti-citrullinated Protein Autoantibodies (ACPA)
Antibodies to Peptidylarginine Deiminase Enzymes
The Etiology and Pathogenesis of Citrullination-Associated Autoantibodies
Origin and Pathogenesis of Citrullination-Associated Antibodies
Mechanisms for Citrullination-Associated Autoantigen Production in the Rheumatoid Joint
Antibodies to Chemically Modified Antigens
Nonspecific Rheumatoid Arthritis Autoantibodies
Conclusion
60. 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
61. Imaging in Rheumatic Diseases
Introduction
Radiography
Computed Tomography
Magnetic Resonance Imaging
Other Imaging Modalities
Conclusion
Part 8. Pharmacology of Anti-rheumatic Drugs
62. 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
63. Glucocorticoid Therapy
Introduction
Characteristics of Glucocorticoids
Genomic and Nongenomic Modes of Action
Glucocorticoid Effects on Hypothalamic-Pituitary-Adrenal Axis
Glucocorticoid Effects on the Immune System
Pharmacology and Clinical Considerations
Glucocorticoid Therapy
Adverse Effects and Monitoring
Future Directions
64. Traditional DMARDs: Methotrexate, Leflunomide, Sulfasalazine, Hydroxychloroquine, and Combination Therapies
Methotrexate
Leflunomide
Anti-malarials
Combination DMARD Therapy in Rheumatoid Arthritis
65. Immunosuppressive Drugs
Introduction
Cyclophosphamide
Azathioprine
Mycophenolate Mofetil
Cyclosporine and Tacrolimus
Conclusion
66. Anti-cytokine Therapies
Introduction
Tumor Necrosis Factor
Interleukin-1
Interleukin-6
Interleukin-12/23
Interleukin-17
Dual Cytokine Inhibition
JAK-STAT Pathway
Monitoring When Treating With Cytokine Blockade
Pregnancy and Breastfeeding
Vaccinations
Conclusion
67. Cell-Targeted Biologics and Emerging Targets: Rituximab, Abatacept, and Other Biologics
Introduction
Targeting B Cells
Targeting Co-stimulatory Molecules
Targeting T Cells
Conclusion
68. Intra-cellular Targeting Agents in Rheumatic Disease
Introduction
Signal Transduction Pathways
p38 MAPK Inhibitors
MEK Inhibitors
Spleen Tyrosine Kinase Inhibitors
Janus Kinase Inhibitors
BTK Inhibitors
PI3K Inhibitors
Sphingosine-1-Phosphate Modulators
Phosphodiesterase Inhibitors
Conclusion
69. Urate-Lowering Therapy
Introduction
Nonpharmacologic Treatment of Hyperuricemia
Xanthine Oxidase Inhibition
Febuxostat
Uricosurics
Uricases
Future Directions
70. Bisphosphonates
Introduction
Clinical Pharmacology
Chemistry of Bisphosphonates
Pharmacokinetics
Treatment Effects and Indications
71. Analgesic Agents in Rheumatic Disease
Introduction
Physiology of Pain Perception (the “Pain Experience”)
Pain Classification
Pharmacologic Treatment of Chronic Pain
Opioids
Anti-depressants
Anti-convulsants
Muscle Relaxants
Emerging Targets
72. Nutrition and Rheumatic Diseases
Introduction
Nutrition and Inflammation
Specialized Proresolving Mediators and N-3 Fatty Acids
Nutrition in the Etiology of Rheumatic Diseases
Nutrition in the Management of Rheumatic Diseases
Conclusion
73. Evaluation and Management of Early Undifferentiated Arthritis
Introduction
Changing Definitions of Classifiable and Undifferentiated Arthritis
Definition of “Early” Arthritis
Evaluation of Early Undifferentiated Inflammatory Arthritis
Management of Early Undifferentiated Arthritis
VOLUME II
Part 9. Rheumatoid Arthritis
74. Etiology of Rheumatoid Arthritis
Introduction
How Rheumatoid Arthritis Begins
Genetic Risk
75. Pathogenesis of Rheumatoid Arthritis
Introduction
Synovial Disease 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
The Synovial Vasculature
Cartilage and Bone Destruction
Conclusion
76. Clinical Features of Rheumatoid Arthritis
Epidemiology and Disease Burden
Pre-clinical Rheumatoid Arthritis
Clinical Presentations of Early Rheumatoid Arthritis
Course and Complications of Established Rheumatoid Arthritis
77. Treatment of Rheumatoid Arthritis
Introduction
Goal of Rheumatoid Arthritis Treatment
Classes of Drugs
Treatment Approaches and Strategies
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
Research Agenda: Unmet Needs
The Horizon
78. 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
79. Etiology and Pathogenesis of Spondyloarthritis
Introduction
Etiology of Spondyloarthritis
Pathogenesis of Spondyloarthritis
Structural Damage in Ankylosing Spondylitis
Current and Future Therapeutic Targets in Spondyloarthritis
80. Ankylosing Spondylitis and Other Forms of Axial Spondyloarthritis
Introduction
Classification
Epidemiology
Genetics
Pathogenesis
Structural Remodeling and Ankylosis
Clinical Manifestations
Physical Examination
Laboratory Tests
Imaging
Diagnosis
Ankylosing Spondylitis in Males and Females
Outcome
Assessment and Monitoring
Conclusion
81. Reactive Arthritis
Reactive Arthritis
Undifferentiated Spondyloarthritis
82. Psoriatic Arthritis
Introduction
Epidemiology
Clinical Features
Differential Diagnosis
Laboratory Features
Radiographic Features
Musculoskeletal Ultrasound
Diagnosis and Classification Criteria
Clinical Course and Outcome
Comorbidities in Psoriatic Arthritis
Outcome Domains and Instruments
Pathogenesis
Pathogenesis Summary
Treatment
Biologics (boDMARDs and bsDMARDs)
Conclusion
83. 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
Assessing and Monitoring Disease Activity
Other Enteropathic Arthropathies
Part 11. Systemic Lupus Erythematosus and Related Syndromes
84. Etiology and Pathogenesis of Systemic Lupus Erythematosus
Introduction
Historic View of Lupus Pathogenesis
Genetic Contributions to Lupus Pathogenesis
Female Predominance of Systemic Lupus Erythematosus
Environmental Triggers of Lupus
Innate Immune System Activation in Systemic Lupus Erythematosus
Adaptive Immune System Alterations in Systemic Lupus Erythematosus
Autoimmunity in Systemic Lupus Erythematosus
Mechanisms of Target Organ Damage
Conclusion
85. Clinical Features of Systemic Lupus Erythematosus
Introduction
Epidemiology
Clinical Features
Diagnosis
Differential Diagnosis
Neonatal Lupus
86. Treatment of Systemic Lupus Erythematosus
Clinical Course and General Treatment Strategy
Patient and Physician Preferences
Drugs Used in the Treatment of Systemic Lupus Erythematosus
Calcineurin Inhibitors
Other Nonbiologic Therapies
Biologic Therapies
Novel Biologics and Currently Tested Therapies
Management of Specific Systemic Lupus Erythematosus Manifestations and Treatment Algorithms
Special Issues: Treat-to-Target, Refractory Disease and Lupus in Pregnancy
Comorbidities
Women’s Health Issues
Evidence and Expert-Based Recommendations in Systemic Lupus Erythematosus
Current Trends and Future Perspectives
87. Antiphospholipid Syndrome
Introduction
Epidemiology
Etiology
Pathogenesis
Clinical Features
Diagnosis and Diagnostic Tests
Treatment
Outcome
Part 12. Systemic Sclerosis, Inflammatory Myopathies, and Overlap Syndromes
88. Etiology and Pathogenesis of Systemic Sclerosis
Introduction
Etiology
Infectious Agents and Viruses
Environmental Exposures, Dietary Factors, Drugs, and Radiation
Microbiome Alterations in Scleroderma or 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 Scleroderma or Systemic Sclerosis
Molecular Determinants of Fibrosis: Transforming Growth Factor-β
Cytokines, Growth Factors, Chemokines, and Lipid Mediators
The Scleroderma Fibroblast
Conclusion
89. Clinical Features and Treatment of Scleroderma
Historical Perspective
Epidemiology
Clinical Features
General Principles of Disease Evaluation
Clinical Manifestations
Treatment
Conclusion of Current Practical Recommendations for Treatment
90. Inflammatory Diseases of Muscle and Other Myopathies
Introduction
Epidemiology
Etiology of Myositis
Pathogenesis
Clinical Features
Classification and Diagnostic Criteria
Physical Findings
Laboratory Findings
Imaging
Electromyography
Pulmonary Function Tests
Differential Diagnosis
Management and Outcome
91. Overlap Syndromes
Introduction
Historical Background
Immunogenetics of Overlap Syndromes
Autoantibodies in Overlap Syndromes
Mixed Connective Tissue Disease
Patients Presenting With Undifferentiated Rheumatic Disease
Treatment of Overlap Connective Tissue Disease Syndromes
Part 13. Vasculitis
92. Classification and Epidemiology of Systemic Vasculitis
Introduction
Classification of Vasculitis
Epidemiology of Vasculitis
93. Giant Cell Arteritis, Polymyalgia Rheumatica, and Takayasu’s Arteritis
Introduction
Giant Cell Arteritis and Polymyalgia Rheumatica
Takayasu’s Arteritis
94. Anti-neutrophil Cytoplasmic Antibody–Associated Vasculitis
Introduction
Classification Criteria and Nomenclature
Epidemiology
Genetics
Clinical Manifestations
Diagnostic Testing
Treatment
Outcome
Pathogenesis
Conclusion
95. Polyarteritis Nodosa and Related Disorders
Polyarteritis Nodosa
Cogan’s Syndrome
Buerger’s Disease
Susac’s Syndrome
Virus-Induced Vasculitis
Infections and Vasculitis
96. Immune Complex–Mediated Small Vessel Vasculitis
Introduction
Pathogenesis
Cutaneous Manifestations
Pathology Features
Differential Diagnosis
Clinical Syndromes
97. Primary Angiitis of the Central Nervous System
Introduction
Epidemiology
Genetics
Clinical Features
Clinical Subsets
Diagnosis and Diagnostic Tests
Differential Diagnosis
Treatment
Outcome
Conclusion
98. Behçet’s Disease
Introduction
Epidemiology
Pathogenesis
Clinical Features
Diagnosis
Treatment
Prognosis
Part 14. Crystal-Induced and Inflammasome-Mediated Inflammation
99. Pathogenesis of Inflammasome-Mediated Diseases
Introduction
Inflammasome Biology
NLRP1
NLRP3
Pyrin
The Pathogenesis of Mevalonate Kinase Deficiency
NLRC4
Other Inflammasomes
Inflammasomes in Autoimmunity
Inflammasome-Targeted Therapies
Conclusion
100. Etiology and Pathogenesis of Hyperuricemia and Gout
Introduction
Evolutionary Considerations
Determinants of Serum Urate Levels
Crystal Formation: The Transition From Hyperuricemia to Gout
Acute Gout Flares: The Inflammatory Response to Monosodium Urate Crystals
Asymptomatic Hyperuricemia
101. Clinical Features and Treatment of Gout
Classification
Clinical Features of Gout
Gout Management
Outcome
102. Calcium Crystal Disease: Calcium Pyrophosphate Dihydrate and Basic Calcium Phosphate
Introduction
Epidemiology
Genetics
Etiology and Pathogenesis
Clinical Features
Articular Basic Calcium Phosphate Crystal Disease
Diagnosis and Diagnostic Tests
Treatment
Outcome
Conclusion
103. Familial Autoinflammatory Syndromes
Introduction
Differential Diagnosis
The Four ‘Classic’ Hereditary Autoinflammatory Syndromes
Other Hereditary Autoinflammatory Syndromes
Conclusion
Part 15. Cartilage, Bone, and Heritable Connective Tissue Disorders
104. Pathogenesis of Osteoarthritis
Introduction
Etiology
Pathology
Alterations in Cartilage Matrix Metabolism
Proteinases
Alterations in Matrix Synthesis
Chondrocyte Senescence
Biomechanics and Disease Mechanisms
Mechanotransduction and Gene Expression
Bone Abnormalities
Role of Inflammatory Mediators in Disease Progression
Conclusion
105. Clinical Features of Osteoarthritis
Introduction
Epidemiology of Osteoarthritis
Clinical Features
Diagnostic Testing
Outcome
Conclusion
106. Treatment of Osteoarthritis
Introduction
Therapeutic Pain Targets in Osteoarthritis
Approach to Management of Osteoarthritis
107. Metabolic Bone Disease
Introduction
Osteoporosis
Treatment
Glucocorticoid-Induced Osteoporosis
Osteomalacia
Paget’s Disease of Bone
Osteoporosis Induced by Other Medications
108. Proliferative Bone Diseases
Introduction
Diffuse Idiopathic Skeletal Hyperostosis
Hypertrophic Osteoarthropathy
SAPHO Syndrome
109. Osteonecrosis
Introduction
Epidemiology
Etiology
Clinical Variants
Staging Osteonecrosis
Pathogenesis
Diagnosis
The Natural History of Osteonecrosis
Treatment of Osteonecrosis
Conclusion
110. Relapsing Polychondritis
Introduction
Epidemiology
Pathology
Pathogenesis
Clinical Features
Associated Disorders
Differential Diagnosis
Diagnostic Tests
Treatment
Outcome
Conclusion
111. Heritable Diseases of Connective Tissue
Introduction
Skeletal Dysplasias
Defects in Extra-cellular Structural Proteins
Osteogenesis Imperfecta
Ehlers-Danlos Syndrome
Marfan Syndrome
Loeys-Dietz Syndrome
Congenital Contractural Arachnodactyly
Conclusion
Part 16. Rheumatic Diseases of Childhood
112. Etiology and Pathogenesis of Juvenile Idiopathic Arthritis
Introduction
Epidemiology
Histopathology
Environmental Triggers of Disease
Host Triggers of Disease
Subtype-Specific Pathogenesis
Conclusion
113. 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 andEnthesitis-Related Arthritis
Juvenile Psoriatic Arthritis
Systemic Juvenile Idiopathic Arthritis
Treatment
Treatment of Juvenile Idiopathic Arthritis Subtypes
Clinical Features and Management of Juvenile Idiopathic Arthritis-Associated Uveitis
Imaging
Outcome
Special Considerations in Children
Conclusion
114. Childhood-Onset Systemic Lupus Erythematosus, Drug-Induced Lupus in Children, and Neonatal Lupus
Childhood-Onset Systemic Lupus Erythematosus
Drug-Induced Lupus
Neonatal Lupus
115. Juvenile Dermatomyositis, Scleroderma, Vasculitis, and Autoimmune Brain Disease
Juvenile Dermatomyositis
Pediatric Scleroderma: Systemic and Localized Forms
Pediatric Vasculitis
Autoimmune Brain Disease
Central Nervous System Vasculitis
Central Nervous System Vasculitis
Autoimmune Encephalitis
Definition/Classification
Epidemiology
Clinical Manifestations
Diagnostic Evaluation
Treatment
Autoimmune Encephalitis Clinical Syndromes
Acquired Demyelinating Syndromes
Part 17. Infection and Arthritis
116. Bacterial Arthritis
Epidemiology
Etiology
Pathogenesis
Clinical Features
Diagnosis and Diagnostic Tests
Treatment
Prosthetic Joint Infections
Conclusion
117. Lyme Disease
Introduction
Ecology and Epidemiology of Lyme Disease
Ticks and Lyme Disease
Pathogenesis
Clinical Features
Lyme Arthritis and Other Musculoskeletal Manifestations of Lyme Disease
Diagnosis
Treatment and Outcome
Outcome
Prevention
Conclusion
118. 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
119. 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
120. Rheumatic Manifestations of HIV Infection
Introduction
HIV-Associated Bone and Joint Disease
HIV-Associated Muscle Disease
Diffuse Infiltrative Lymphocytosis Syndrome
Vasculitis Associated With HIV Infection
Primary Pulmonary Hypertension
HIV-Associated Musculoskeletal Infection
Response of Other Rheumatic Diseases to HIV Infection
Highly Active Anti-retroviral Therapy-Related Immune Reconstitution Syndrome
Rheumatologic Laboratory Abnormalities Associated With HIV Infection
Conclusion
121. Viral Arthritis
Introduction
Examples of Arthritogenic Viruses
Treatment and Prevention
Conclusion
122. Rheumatic Fever and Post-streptococcal Arthritis
Introduction
Rheumatic Fever and Rheumatic Heart Disease
Post-streptococcal Arthritis
Conclusion
Part 18. Arthritis Accompanying Systemic Disease
123. Amyloidosis
Introduction
AA Amyloidosis
Other Types of Systemic Amyloidosis
Diagnosis and Diagnostic Tests
Treatment of AA Amyloidosis
Outcome
Conclusion
124. Sarcoidosis
Introduction
Classification Criteria
Epidemiology
Etiology
Genetics
Pathogenesis
Clinical Features
Diagnosis and Diagnostic Tests
Treatment
Outcome and Prognosis
Conclusion
125. 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
Outcome
Conclusion
126. Hemophilic Arthropathy
Introduction
Clinical Features
Diagnosis
Pathogenesis
Treatment of Hemophilia
Treatment of Musculoskeletal Complications
Conclusion
127. Rheumatic Manifestations of Hemoglobinopathies
Introduction
Thalassemias
Sickle Cell Anemia and Related Disorders
Diagnosis
Treatment
Musculoskeletal Involvement: Sickle Cell Disease
Musculoskeletal Involvement: Thalassemias
Comorbid Rheumatic Disease
Conclusion
128. IgG4-Related Disease
Introduction
Epidemiology
Pathology Features
Serum IgG4 Concentrations
Pathophysiology
Clinical Manifestations
Differential Diagnosis
Treatment
129. Arthritis Accompanying Endocrine and Metabolic Disorders
Introduction
Adrenal Gland Disorders
Acromegaly
Hypothalamic-Gonadal Axis
Diabetes Mellitus
Hyperthyroidism
Hypothyroidism
Hypoparathyroidism
Hyperparathyroidism
Lipid Disorders
130. Rheumatic Paraneoplastic Syndromes—Links Between Malignancy and Autoimmunity
Introduction
Paraneoplastic Arthritis (PA)
Palmar Fasciitis and Polyarthritis Syndrome (PFPAS)
Remitting Seronegative Symmetrical Synovitis With Pitting Edema (RS3PE)
Pancreatic Panniculitis and Polyarthritis (PPP)
Erythromelalgia
Paraneoplastic Vasculitis
Cancer-Associated Myositis (CAM)
Hypertrophic (Pulmonary) Osteoarthropathy (HOA)
Tumor-Induced Osteomalacia (TIO)
Conclusion
131. Tumors and Tumor-like Lesions of Joints and Related Structures
Introduction
Non-neoplastic Lesions
Neoplasms
Malignant Tumors of the Joint
132. Autoimmune Complications of Immune Checkpoint Inhibitors for Cancer
Introduction
Immune-Related Adverse Events (irAEs)
Rheumatologic Immune-Related Adverse Events
Treatment of Rheumatologic Immune-Related Adverse Events
Pre-existing Autoimmune Disease and Immune Checkpoint Inhibitor Use
Index
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

Ralph C. Budd

Affiliations and expertise

Professor of Medicine and Microbiology and Molecular Genetics, Director, Vermont Center for Immunology and Infectious Diseases, University of Vermont College of Medicine Distinguished University Professor, The University of Vermont College of Medicine, Burlington, Vermont

Sherine E Gabriel

Affiliations and expertise

Professor and Dean, Rutgers Robert Wood Johnson Medical School, CEO, Robert Wood Johnson Medical Group, Emeritus Professor, Mayo Clinic, New Brunswick, New Jersey

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

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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