Rheumatology, 2-Volume Set - E-Book
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Written and edited by international leaders in the field, Rheumatology, 9th Edition, seamlessly blends the latest scientific advances in rheumatology with real-world clinical insights, making it an essential resource for rheumatology specialists and fellows. This comprehensive, two-volume reference uses an easy-to-follow, templated format with concise text and cutting-edge illustrations, covering key topics such as epidemiology, physical examination, pathogenesis, clinical features, therapeutic strategies, and management of both common and rare rheumatic diseases.
New contributing authors, new content throughout, and up-to-date coverage of new breakthroughs in the treatment of lupus, rheumatoid arthritis, and more keep you abreast of recent changes in this fast-changing field.Covers the epidemiology, pathogenesis, clinical manifestations, therapeutic approach, and management of all major as well as rarely encountered rheumatic and musculoskeletal diseasesContains new content on artificial intelligence and machine learning; sex/gender influences, environmental triggers, new and emerging diseases, the potential impact of clonal hematopoiesis to the field of rheumatology, and moreDetails new immunologic approaches such as cellular therapies, activation of T cell checkpoints, induction of tolerance, and pain pathways in synovial-based diseasesDiscusses clinical examination, imaging principles, differential diagnosis, established and novel therapies, perioperative evaluation, pain management, basic science, and genetics of rheumatic and musculoskeletal diseasesUses a consistent, logical, reader-friendly format with templated chapters, concise text, and large-scale, state-of-the-art illustrations for efficient visual referenceProvides access to high-quality videos depicting the use of ultrasound for diagnosis and treatmentAny additional digital ancillary content may publish up to 6 weeks following the publication date
Nánar um bókina
- Elsevier Limited (UK)
- 9780443283703
- 9780443283697
- ePub
- 9
- Marc C. Hochberg
- English
- 2026-12-28
- 10
- 2
- 2
Kaflar
- Instructions for online access
- Title of Book
- Cover image
- Title page
- Table of Contents
- Dedication
- Contributors
- Preface
- Acknowledgments
- Video Contents
- Volume One
- Scientific Basis of Rheumatic Disease
- A Anatomy and Physiology
- 1 The Synovium
- Key Points
- Definitions
- Embryology
- Structure
- Cell Types Found in the Synovium as Revealed by Single-Cell Analysis
- Intimal Cells
- Synovial Macrophages
- Synovial Fibroblasts and the Stroma
- Intimal Matrix
- Vascular Network
- Cell Origins and Recruitment
- Function
- Maintenance of the Tissue Surface
- Lubrication
- Chondrocyte Health and Nutrition
- Synovium as a Target for Immune-Mediated Disease
- Summary
- 2 The Articular Cartilage
- Key Points
- Overall Tissue Organization
- Aggrecan
- Collagen Fibrillar Networks
- Fibers With Collagen Type II as the Main Constituent
- Molecules Regulating Collagen Fiber Assembly
- Fibers and Networks With Collagen Type VI as the Main Constituent
- Molecules Interacting at the Cell Surface and Modulating Chondrocyte Behavior
- Integrin-Binding Proteins
- Discoidin Domain 2–Containing Receptor
- Hyaluronan
- Ligands for Heparin Sulfate/Syndecans
- Other Molecular Functions
- Binding and Sequestering Growth Factors in the Extracellular Matrix
- Other Molecules in the Extracellular Matrix
- Matrix Protein Fragments as Indicators of Disease
- Repair and Regeneration of Cartilage
- Replacing Cartilage
- Microfracture
- Implanted Cell-Based Therapies
- Autologous Chondrocyte Implantation
- Stem/Progenitor Cells of Other Tissues
- Progenitor Cells of Articular Cartilage
- Tissue-Engineered Cartilage
- 3 Bone Structure and Function
- Key points
- Macroscopic and Microscopic Organization of the Bone
- Collagen
- Mineral
- Water
- Additional Minor Components
- Cellular and Molecular Composition of Bone
- Growth, Modeling, Remodeling, and Repair
- Growth
- Modeling
- Remodeling
- Repair
- Mechanical Adaptation
- 4 Tendons and Ligaments
- Key Points
- Introduction
- Classification and Diagnosis of Disease Affecting Tendons and Ligaments
- Etiology of Tendinopathy, Enthesopathy, and Desmopathy
- Pathophysiology of Tendons and Ligaments
- Tendon and Ligament Extracellular Matrix in Health and Disease
- Inflammation Activation Pathways Show Plasticity in Tendon Disease
- Fibroblast Activation in Tendon Disease
- Fibrotic Progression in Healing Tendons
- The Tendons and Ligaments in High Resolution
- Diseased Tendons Show Dysregulated Resolution Responses
- Treatment of Tendon and Ligament Pathology
- Surgical Treatments
- Medical Treatments
- Evidence from Randomised Controlled Trials of Tendon Therapies
- Conclusions and Future Perspectives
- 5 Biomechanics of Peripheral Joints and Spine
- Key Points
- Introduction
- Biomechanics of Whole Joints and Spine
- Whole-Joint Movement
- Mechanical Function of the Spine
- Spinal Movements
- Statics and Dynamics
- Joint Lubrication
- Biomechanics of Tissues
- Structural and Material Properties
- Stress and Strain
- Viscoelasticity
- Forces Acting on the Spine
- Muscle Forces
- Intraabdominal Pressure
- Diurnal Variation
- Measurement of Spinal Loading in Vivo
- Intervertebral Disk Mechanics
- Resistance to Compression, Shear, Torsion, and Bending
- 6 The Neurobiology of Pain in Arthritis
- Key Points
- Introduction
- The Pain Pathway: An Overview
- The Nociceptive Pathway
- Pain Pathways in Rheumatic Diseases
- RMDs are Characterized by Signs of Sensitization of the Nociceptive Pathway
- Genetics of Pain in Rheumatic Diseases Suggest Underlying Neurobiological Mechanisms
- Emerging Insights into the Neurobiology of Pain in RMDs
- Sex Differences in Nociceptive Pathways
- Obesity and Adiposity as Pain–Driving Factors
- Conclusions
- B Immunology and Inflammation
- 7 Principles of Innate Immunity
- Key Points
- Introduction
- Sensing by innate immunity
- Signaling sensors
- Internalizing sensors
- Soluble sensors
- Phylogenetic comparison of the recognition system
- Critical functions of innate immunity
- Activation of adaptive immunity
- Antiviral responses
- Molecular mechanism of sensor signaling
- Sensors and diseases
- Toll-like receptors and autoimmunity
- Type I interferonopathies
- Toll-like receptors and metabolic diseases
- NOD-like receptors and inflammation
- Conclusion
- 8 Principles of Adaptive Immunity
- Key Points
- Introduction
- The Adaptive Immune System
- Clonal Selection and Expansion of Lymphocytes
- Antigen Receptors of Lymphocytes
- Generation of Diversity of Antigen Receptors
- B Cells and Humoral Immunity
- B-Cell Activation and Functions
- T Cells and Cell-Mediated Immunity
- Processing of Antigens for Presentation to T Cells
- T-Cell Development
- T-Cell Activation
- T-Cell Function
- Immunologic Tolerance and Autoimmunity
- Conclusion
- 9 Signal Transduction in Immune Cells
- Key Points
- Introduction
- Membrane-Permeable Ligands That Bind Intracellular Receptors
- Steroid Hormone Receptors With Ligand-Binding, DNA-Binding, and Transactivation Domains
- Receptors With Intrinsic Enzymatic Activity
- Receptors That Associate With Enzymes
- Type I and Type II Cytokine Receptors
- Antigen Receptors and FC Receptors: The Multichain Immune Recognition Receptor Family
- Tumor Necrosis Factor Receptor Superfamily
- Innate Recognition of Pathogens
- G Protein–Coupled Receptors
- Summary
- 10 Clonal Hematopoiesis and Rheumatologic Diseases
- Key Points
- Introduction
- Clonal Hematopoiesis: Terminology and Epidemiology
- Risk Factors for CH
- Adverse Outcomes in Clonal Hematopoiesis
- Systemic Inflammatory and Autoimmune Diseases (SIAD)
- Management of Clonal Hematopoiesis
- 11 Cytokines
- Key Points
- Introduction
- Interleukin-1 Receptor Family
- Family Members and Their Action
- Signal Transduction
- Tumor Necrosis Factor Receptor Superfamily
- Tumor Necrosis Factor–Family Receptor Signaling
- Tumor Necrosis Factor Receptor Family Members and Their Actions
- Type I and II Cytokine Receptors: Hematopoietin and Interferon Receptors
- Cytokines That Use Glycoprotein 130: Interleukin-6 as a Prototype
- Cytokine Receptors Using the β Chain: Interleukin-3, Interleukin-5, and Granulocyte-Macrophage Colony-Stimulating Factor
- Cytokine Receptors Using the γ Chain: Interleukin-2, Interleukin-4, Interleukin-7, Interleukin-9, Interleukin-15, and Interleukin-21
- Homodimeric Receptors
- Heterodimeric Cytokines
- Interferons
- Interleukin-10 Family
- Signaling by Type I/II Cytokine Receptors
- Interleukin-17 Receptors
- Transforming Growth Factor-β Receptor Family Cytokines
- Signaling
- Receptor Tyrosine Kinases
- Other Cytokines
- Chemokines
- Family Members and Their Actions
- The Immune Dictionary
- 12 Inflammation and Its Chemical Mediators
- Key Points
- Introduction
- The Cells of Inflammation
- Endothelial Cells Promote Leukocyte Ingress to Tissues
- Granulocytes Directly Attack Pathogens
- Macrophages Clear Pathogens and Maintain Homeostasis
- Platelets
- Regulation and Modulation of Inflammatory Cells
- Trained Immunity, or Innate Immune Memory
- Soluble Inflammatory Mediators
- The Complement System
- Lipid Mediators of Inflammation
- Vasoactive Amines
- Reactive Oxygen Species and Nitric Oxide
- The Nervous System in Inflammation
- Autonomic Influence on Inflammation
- Neuroendocrine Mechanisms
- Neuropeptides
- The Resolution of Inflammation
- Elimination of the Inciting Stimulus and Proinflammatory Signals
- Removal of Inflammatory Cells
- Lipoxins, Resolvins, and Other Soluble Antiinflammatory Mediators
- Tissue Repair after Resolution of Inflammation
- The Aging Inflammatory System: Immunosenescence and Inflammaging
- 13 The Complement System
- Key Points
- Classical Pathway 12
- Mannose-Binding Lectin Pathway 15
- Alternative Pathway
- Anaphylatoxins 22
- Regulation of the Complement System
- Complement in Disease
- Complement in Autoimmunity
- Complement in Inflammatory Diseases
- Strategies for Therapeutically Targeting Complement
- Conclusions
- 14 Osteoimmunology
- Key Points
- Introduction
- Current Concepts in Osteoimmunology
- Osteoclasts as Triggers of Arthritic Bone Erosions
- Molecular and Cellular Mechanisms of Inflammatory Bone Erosion
- Metabolic Regulation of Osteoclasts in Inflammatory Conditions
- Intraarticular and Systemic Bone Loss in Rheumatic Disease
- Osteoimmunologic Aspects of Bone Formation in Rheumatic Disease
- Bone Marrow as a Niche for B-Cell Differentiation and Autoantibody Formation
- Conclusion
- 15 Joint Tissue Destruction and Proteolysis
- Key Points
- Introduction
- Proteolytic Pathways of Connective Tissue Breakdown
- Extracellular Proteolysis
- Regulation of MMPs and Their Inhibitors by the ECM
- Other Proteinases Involved in Pathological Joint Destruction
- Serine Proteinases
- Intracellular Pathways
- Osteoclastic Bone Resorption
- Model Systems of Joint Destruction
- In Vitro, Ex Vivo, and Silico Models
- In Vivo Models
- Proteinase Deficiency in Murine Models of Arthritis
- Therapeutic Inhibition of Proteinases
- Repair of Connective Tissue Matrix
- Summary
- 16 Principles of Tissue Engineering
- Key Points
- Introduction
- Cell Sources
- Biomaterial Scaffolds and Scaffold-Free Approaches
- Biochemical and Biophysical Signals
- Tissue Engineering for Arthritis Management
- Rheumatoid Arthritis
- Osteoarthritis
- Emerging Trends of Tissue Engineering–Enabled Arthritis Therapies
- Acknowledgment
- C Systems Biology
- 17 Big Data Analysis
- Key Points
- What Is Big Data?
- Sources of Big Data in Rheumatology
- Clinical Data
- Challenges and Considerations in the Analysis of Big Clinical and Health Data
- Biological Data
- Application and the Future of Big Data
- Ethics and Governance
- 18 Artificial Intelligence in Rheumatology
- Key Points
- Introduction
- The Landscape of AI
- AI and Its Subfields
- Core AI Methods
- Overview of Core Methods
- Supervised Learning: Label–Guided Learning
- Unsupervised Learning: Discovering Hidden Structure
- Transfer and Semisupervised Learning (Leveraging Pretrained Models)
- Foundational Models: Architecture, Function, and Relevance in Modern AI
- Evaluating AI Models in Clinical Research and Practice
- Study Design Quality
- Metrics That Matter: Beyond Accuracy
- Best Practices in Validation and Reproducibility
- Quality Assessment of Clustering Approaches and Clinical Interpretability
- Assessing the Quality of LLM–Based Research
- Regulatory and Ethical Issues
- Ethical Considerations: Transparency, Accountability, and Algorithmic Bias
- Patient Privacy, Data Protection Laws, and Informed Consent
- Integrated AI Tools in Medicine and Rheumatology
- AI in Medicine: Current Landscape and Key Domains
- AI in Rheumatology: Applications and Developments
- Conclusion and Future Directions
- 19 Principles and Techniques in Molecular Biology
- Key Points
- Introduction
- The Human Genome Sequence and Biomedical Research
- Manipulation of DNA: Cloning Vectors and Cutting and Pasting DNA Using Enzymes
- Polymerase Chain Reaction
- DNA Sequencing
- Gene Transcription
- Gene Expression Profiling
- DNA Chip Microarrays
- Massively Parallel Sequencing of RNA
- Single Cell RNA Sequencing
- Spatial Transcriptomics
- Regulation of Gene Expression and Protein-DNA Interactions
- Analysis of Gene Function
- Genetic Manipulation of Mice
- Transgenic Mice
- Knockout Mice
- Mice With Cre/lox-Directed Targeted Disruption
- CRISPR-Cas9 and Genome Editing
- Analysis of Proteins
- Proteomics
- Chimeric Antigen Receptor T-Cell Therapy
- Molecular Biology: The New Pathology for Practicing Rheumatologists?
- 20 Proteomics
- Key Points
- Proteomics—A Powerful New Tool for Personalized Medicine
- Main Proteomics Technologies
- Expression Proteomics
- Interaction Proteomics
- Thermal Shift Proteomics
- Posttranslational Modification Proteomics
- Yeast Two-Hybrid Assay
- Mammalian-Membrane Two-Hybrid Assay
- Nucleic Acid Programmable Protein Arrays
- Affinity Proteomics
- How Can Proteomics Help Rheumatology?
- Outlook
- 21 Metabolomics in Rheumatology
- Key points
- We Are What We Eat: Metabolism Has Driven Our Development
- Metabolism Underpins Musculoskeletal Function
- Inflammation Perturbs Metabolism
- Metabolism and Immune Inflammation
- Metabolism in Rheumatology
- Metabolomics
- Acquiring Metabolomics Data
- Making Sense of the Data
- Applications of Metabolomics in Rheumatology
- Rheumatoid Arthritis
- Metabolomics and Other Rheumatic Diseases
- The Gut Microbiome
- Systemic Metabolic Effects
- Responses to Therapy
- Conclusions
- 22 Epigenetics
- Key Points
- What Is Epigenetics
- Transcriptional Control Through Epigenetic Mechanisms
- Molecular Epigenetics—The Basic Mechanisms
- Histone Modifications
- DNA Modifications
- Epigenetics in Disease
- The Origin of Epigenetic Alterations
- Rheumatic Diseases and Epigenetic Changes
- Systemic Lupus Erythematosus and Sjögren’s Disease
- Rheumatoid Arthritis
- Other Rheumatic Diseases
- 23 Polygenic Risk Scores and Rheumatic Diseases
- Key Points
- Introduction
- What Is Polygenic Risk Score?
- Development of PRSs
- Genetic Diagnostic Markers in Rheumatology
- PRSs in Rheumatic Diseases
- Rheumatoid Arthritis
- Ankylosing Spondylitis
- Systemic Lupus Erythematosus
- Systemic Sclerosis
- Gout
- Psoriatic Arthritis
- Osteoarthritis
- Osteoporotic Fracture
- Sjögren’s Syndrome
- Clinical Utility
- Conclusion
- 24 Precision Medicine in Rheumatology
- Key Points
- Introduction
- Potential Advances in Rheumatology by Way of Precision Medicine
- Stratifying and Treating Based on Molecular Patterns
- Identifying Shared Molecular Patterns and Treatment Options Across Conditions
- Novel Targets for Precision Medicine in Rheumatology
- T Cell and B Cell Receptor Clones
- Clones with Somatic Mutations
- NoveL Therapeutic Designs for Precision Rheumatology
- Bispecific Biologics
- Future Directions
- Acknowledgment
- 25 The Microbiome in Rheumatic Diseases
- Key Points
- Introduction
- The microbiome
- Mucosal barriers and host-immune interactions
- Dysbiosis as a trigger for autoimmunity
- Research methods for study of the human microbiome
- The microbiome in animal models of inflammatory arthritis
- The microbiome in human inflammatory arthritis
- Spondyloarthritis
- Inflammatory bowel disease–related arthropathy
- Psoriasis and psoriatic arthritis
- Rheumatoid arthritis
- The microbiome in systemic lupus erythematosus
- Pharmacomicrobiomics
- Manipulating the microbiome to modulate autoimmune disease
- Conclusion
- Section 2 Clinical Basis of Rheumatic Disease
- 26 Principles of Epidemiology
- Key points
- Introduction
- What can epidemiologic methods accomplish?
- What will be covered in this chapter?
- How to study and define populations
- Defining the pieces of an epidemiologic study
- Defining Outcome
- Descriptive epidemiology
- Analytic epidemiology
- Other study designs
- Measures
- Some notes about measures and modeling
- Types of bias
- Confounding
- Selection bias
- Immortal time
- Misclassification
- Generalizability
- Summary
- 27 Principles of Clinical Outcome Assessment
- Key Points
- Introduction
- Purpose of Measuring a Clinical Outcome
- Measurement Science Attributes
- Validity
- Reliability
- Responsiveness
- Interpretability
- Examples of Clinical Outcome Assessment
- Multidimensional Health Status Instruments
- Assessment of Adverse Reactions
- Measurement in Clinical Trials
- Conclusion
- 28 Principles of Health Economics
- Key Points
- Background
- The Concept of Economic Evaluation
- Perspective
- Methodology of Economic Evaluations
- Interpretation of Economic Evaluations
- Transferability of Health Economic Evaluations
- Healthcare Decisions
- Economic Evaluations and Efficiency in Daily Practice
- Conclusions
- 29 Principles of Genetic Epidemiology
- Key Points
- Introduction
- Familial aggregation
- Twin studies
- Gene mapping
- Looking beyond associations
- Next steps
- Acknowledgment
- 30 Interpreting the Medical Literature for the Rheumatologist
- Key Points
- Introduction
- Levels of Evidence
- Randomized Controlled Trials or Observational Studies?
- Critical Appraisal I: Issues Pertaining to Randomized Controlled Trials
- Efficacy Versus Effectiveness
- Superiority Trials and Noninferiority Trials
- Statistical Power
- Intention-To-Treat Analysis
- Subgroup Analyses
- Critical Appraisal II: Issues Pertaining to Observational Studies
- Selection Bias
- Critical Appraisal III: Issues Pertaining to Randomized Controlled Trials and Observational Studies
- Missing Data
- Data Interpretation
- The Statistical Test
- Conclusion
- 31 Ethics in Clinical Trials
- Key Points
- Introduction
- “Ethical Guardrails” in Clinical Research
- Key Principles for Ethical Clinical Trials
- Selected Challenges in Clinical Trial Ethics
- Future Challenges in Clinical Trial Ethics
- Conclusion
- Section 3 Approach to the Patient
- 32 History and Physical Examination
- Key Points
- Introduction
- Screening assessment
- Screening history
- Screening examination
- Assessing a musculoskeletal problem
- The consultation to assess a musculoskeletal problem: key components
- Interpretation
- Joint problems
- Regional pain problems
- Generalized pain problems
- Neck or back problems
- Muscle problems
- Bone disorders
- Systemic problems with musculoskeletal symptoms
- Communicating the findings
- 33 Laboratory Tests in Rheumatic Disorders
- Key Points
- Introduction
- Laboratory Tests in Rheumatic Diseases
- Blood Cell Counts
- Platelets
- Red Blood Cells
- Biochemical Testing
- Alkaline Phosphatase
- Kidney Function Tests and Urinalysis
- Serologic Testing
- Complement
- Conclusion
- 34 Aspiration and Injection of Joints and Periarticular Tissue and Intralesional Therapy
- Key Points
- Indications for Aspirating or Injecting Musculoskeletal Tissues
- Key Practice Issues
- Aftercare
- Contraindications
- Corticosteroid Injections
- Other Therapeutic Injections
- Wrist and Hand
- First Carpometacarpal Joint
- Wrist (Radiocarpal and Midcarpal Joints, Distal Radioulnar Joint)
- Trigger Finger and Trigger Thumb
- Digital Flexor Tenosynovitis
- Carpal Tunnel Syndrome 45
- De Quervain Tenosynovitis 47
- Wrist Extensor Tenosynovitis
- Ganglia
- Elbow Region
- Olecranon Bursa
- Lateral Epicondylar Syndrome, or Tennis Elbow, and Medial Epicondylar Syndrome, or Golfer’s Elbow 49 , 50
- Shoulder Region
- Acromioclavicular Joint
- Subacromial Bursa
- Rotator Cuff Calcific Tendinopathy
- Long Head of the Biceps Brachii Tendon
- HIP Region
- Iliopsoas Bursa
- Trochanteric Syndrome
- Knee Region
- Baker Cyst
- Medial Knee Pain and Pes Anserinus Syndrome
- Ankle and Foot
- Subtalar Joint
- Metatarsophalangeal Joints
- Retrocalcaneal Bursa
- Posterior Tibialis Tendon (Ptt), Peroneal Tendon, Extensor and Flexor Tendon Sheath
- Plantar Fascia Calcaneal Enthesis 60
- Intermetatarsal Bursae
- Morton Neuroma 61
- Intralesional Corticosteroid Treatment
- 35 Synovial Fluid Analysis
- Key Points
- Macroscopic Characterization
- Microscopic Analysis
- Wet-Preparation Microscopy
- Cell Counts
- Crystal Detection
- MSU Crystals
- CPP Crystals
- BCP Crystals
- Lipids
- Glucocorticoid Crystals
- Other Crystalline Contents of SF
- Non-crystalline Particulate Matter
- Ragocytes
- Cytocentrifuge Preparation
- Bacterial and Septic Arthritis
- Non-bacterial Infections
- Synovial Fluid Cytology
- Future Directions
- Summary
- Acknowledgements
- 36 Minimally Invasive Procedures
- Key Points
- Introduction
- Arthrocentesis
- Biopsies
- Skin and Subcutaneous Tissue
- Abdominal Fat Pad Fine-Needle Aspiration
- Temporal Artery
- Muscle and Fascia
- Salivary Glands
- Synovium
- 37 The Skin in Rheumatic Disease
- Key Points
- Introduction
- Approach to the Patient
- Major Systemic Connective Tissue Disorders
- Dermatomyositis
- Systemic Sclerosis
- Sjögren Syndrome (Sicca Syndrome)
- Other Systemic Rheumatic Diseases
- Juvenile Idiopathic Arthritis
- Relapsing Polychondritis (Atrophic Polychondritis, Systemic Chondromalacia, Polychondropathia)
- Psoriatic Arthritis
- 38 Ocular manifestations of rheumatic diseases
- Key Points
- Introduction
- Uveitis
- Management
- Scleral Disease
- Management
- Retinal Vascular Disease
- Optic Nerve Disease
- Orbital Disease
- Corneal Disease
- Keratoconjunctivitis Sicca
- 39 The Cardiovascular System in Rheumatic Disease
- Key Points
- Introduction and Overview
- Coronary Artery Disease
- Prevention of Coronary Events in Rheumatologic Conditions
- Atypical Coronary Disease in SARDs
- Coronary Arteritis
- Functional Coronary Artery Disorders
- Hypertension
- Heart Failure and Direct Myocardial Involvement
- Valvular Heart Disease
- Pericarditis
- Arrhythmias
- Pulmonary Hypertension
- Medication and the Heart
- Conclusion
- 40 The Lungs in Rheumatic Disease
- Key Points
- Introduction
- Interstitial Lung Disease
- Pathologic and Radiologic Features in Interstitial Lung Disease
- Evaluation of Patients With Interstitial Lung Disease in the Rheumatic Diseases
- Radiographic Studies
- Pulmonary Function Testing
- Bronchoscopy
- Surgical Lung Biopsy
- Ancillary Studies
- Lung Involvement in Rheumatic Diseases
- Rheumatoid Arthritis
- Dermatomyositis and Polymyositis
- Systemic Lupus Erythematosus
- Sjögren Syndrome
- Interstitial Pneumonia With Autoimmune Features
- Drug-Induced Lung Injury
- Lung and Vasculitic Syndromes
- Treatment of Interstitial Lung Disease Associated With the Rheumatic Diseases
- Conclusion
- 41 The Gastrointestinal Tract in Rheumatic Disease
- Key Points
- Introduction
- Inflammatory Bowel Disease: Crohn Disease and Ulcerative Colitis
- Extraintestinal Manifestations of Inflammatory Bowel Disease
- Peripheral Arthritis and Arthralgia Associated With Inflammatory Bowel Disease
- Axial Arthritis Associated With Inflammatory Bowel Disease
- Bacterial Enteritis
- Celiac Disease
- Whipple Disease
- Polyarteritis Nodosa
- Henoch-Schönlein Purpura
- Behçet Disease
- Microscopic Colitis
- Conclusion
- 42 The Kidneys in Rheumatic Disease
- Key Points
- Introduction
- Approach to the Patient with Rheumatologic Disease and Suspected Kidney Disease
- Acute versus Chronic Kidney Disease
- Glomerular Disease: Nephrotic versus Nephritic
- Diagnostic Tools for the Identification of Kidney Disease
- Serum Creatinine
- Proteinuria: Urinary Albumin or Protein Excretion Rate
- Hematuria
- Leukocyturia, Eosinophiluria, and Urinary Casts
- Electrolytes and Acid–Base Status
- Plasma Complement Levels
- Imaging Studies
- Kidney Biopsy
- Kidney Involvement in Rheumatologic Diseases ( Table 42.3 )
- Infection-Related Rheumatic Diseases
- Spondyloarthritis and Psoriatic Arthritis
- Systemic Lupus Erythematosus and Related Diseases
- Systemic Sclerosis/Scleroderma
- Inflammatory Muscle Disease
- Vasculitides
- Other Systemic Illnesses
- Crystal-Related Arthropathies
- Nephrotoxicity of Antirheumatologic Pharmacologic Therapy
- Calcineurin Inhibitors: Cyclosporine and Tacrolimus
- Disease-Modifying Antirheumatic Drugs and Biologic Agents
- Rheumatologic Complications of Kidney Disease
- Etiologic Factors Specific to Kidney Failure and Their Associated Rheumatic Syndromes
- Clinical Features of CKD-MBD: Bone Disorder and Turnover
- Rheumatologic-Associated Issues Postkidney Transplantation
- 43 The Nervous System in Rheumatic Disease
- Key Points
- Introduction
- Peripheral Nervous System
- Distal Neuropathy
- Cranial Neuropathy
- Optic Neuropathy
- Trigeminal Neuropathy
- Facial Palsy
- Multiple Mononeuropathies
- Nonlength-Dependent Neuropathy
- Central Nervous System
- Meningitis
- Encephalitis
- Myelitis
- Conclusion
- 44 The Muscles in Rheumatic Disease
- Key Points
- Introduction
- Skeletal Muscle Anatomy and Architecture
- Normal Muscle Contractile Function
- Muscle Involvement in Rheumatologic Conditions
- Idiopathic Inflammatory Myopathies
- Metabolic Myopathies
- Cachexia Associated With Rheumatological Diseases
- Drug-Induced Myopathy
- Generalized Myalgia
- Clinical Assessment of Skeletal Muscle
- Muscle Biopsy
- Magnetic Resonance Imaging
- Manual Muscle Testing
- Acknowledgment
- Section 4 Evaluation of the Patient: Imaging Techniques
- 45 Conventional Radiography and Computed Tomography
- Key Points
- Conventional Radiography
- Uses
- Choice of Joints
- Techniques and Physics
- Computed Tomography
- Applications in Rheumatology
- Dual-Energy Computed Tomography
- 46 Magnetic Resonance Imaging
- Key Points
- Introduction
- Basic Principles
- T2 Relaxation
- T1 Relaxation
- Magnetic Resonance Imaging Contrast
- Image Quality
- Conventional Magnetic Resonance Imaging Methods
- Two-Dimensional Fast Spin-Echo Imaging
- Three-Dimensional Gradient-Echo Techniques
- Advanced Magnetic Resonance Imaging Techniques
- Parallel Imaging
- Balanced Steady-State Free Precession Imaging
- Three-Dimensional Fast Spin-Echo Imaging
- High-Field Magnetic Resonance Imaging
- Cartilage Thickness and Volume Mapping
- Magnetic Resonance Imaging to Demonstrate Physiologic Activity
- Positron Emission Tomography and Magnetic Resonance Imaging
- Artificial Intelligence, Machine Learning, and Super-Resolution
- Conclusion
- 47 Musculoskeletal Ultrasonography
- Key Points
- Introduction
- Musculoskeletal Ultrasound Imaging
- Ultrasound Equipment
- Education and Training
- Standard Views and Artifacts
- Musculoskeletal Ultrasonography in Rheumatology
- Tendon and Enthesis
- Dactylitis
- Muscle
- Bone Erosion and Osteophyte
- Cartilage
- Soft Tissue Calcification and Crystal-Induced Arthritis
- Noninflammatory Soft Tissue Disorders
- Spine and Sacroiliac Joint
- Intervention
- Nonmusculoskeletal Tissue Ultrasonography in Rheumatology
- Peripheral Nerves
- Vasculitis
- Parotid and Salivary Glands
- Skin and Nail
- Conclusion
- 48 Bone Scintigraphy and Positron Emission Tomography
- Key Points
- Introduction
- Bone Scintigraphy
- Uses
- Positron Emission Tomography
- Uses
- Practical Issues
- 49 Dual X-Ray Absorptiometry and Measurement of Bone
- Key Points
- Introduction
- Diagnosis of Osteoporosis
- Skeletal Sites to Measure
- Using Non-Dual X-ray Absorptiometry Technologies for Osteoporosis Diagnosis
- Technical Aspects of DXA
- Indications for Bone Mineral Density Testing
- Vertebral Fracture Assessment
- Fracture Risk Assessment
- Bone Mineral Density
- Clinical Risk Factors and Fracture Risk Assessment Tools
- Bone Turnover Markers
- Other Modalities for Fracture Risk Assessment
- Monitoring of Therapy
- Quantitative Computed Tomography and Peripheral Computed Tomography
- Quantitative Ultrasonography
- Biochemical Bone Turnover Markers
- Bone Turnover Markers After Discontinuing Therapy
- Evaluation of Cortical and Trabecular Bone
- High-Resolution Peripheral Quantitative Computed Tomography
- Finite Element Analysis (FEA)
- Bone Material Strength as Measured by Microindentation
- Bone Biopsy
- Conclusions
- 50 Use of Imaging as an Outcome Measure in Clinical Trials
- Key Points
- Introduction
- General Aspects for Clinical Trials
- Different Phases of Drug Development
- Readers
- Assessment of Reader Agreement
- Grouping of Films—Read Sessions
- Blinding Time Sequence
- Presentation of Data
- Statistical Handling of Missing Data
- Statistical Analyses
- Minimum Duration of Trial
- Placebo Versus Active Comparator
- Rheumatoid Arthritis
- Scoring Methods
- Magnetic Resonance Imaging and Ultrasonography
- Psoriatic Arthritis
- Scoring Methods
- Magnetic Resonance Imaging and Ultrasonography
- Axial Spondyloarthritis
- Magnetic resonance imaging and ultrasonography
- Principles of Management
- A General
- 51 The Patient Perspective on Health Care
- Key Points
- Introduction
- Patients’ Perception of Remission and Flares
- Patient-Centered Care
- Holistic Approach
- Patient-Reported Outcomes
- Shared Decision Making
- Self-Management
- Multidisciplinary Team Care
- Organization of Care
- Patient Education
- Conclusion
- 52 Treatment Recommendations and “Treat-to-Target”
- Key Points
- General Treatment Approaches to Rheumatic Diseases
- Incorporating Patient Preferences Through Shared Decision Making (SDM)
- Treat-to-Target Concept
- Treat-to-Target for Rheumatoid Arthritis
- Treat-to-Target for Psoriatic Arthritis
- Treat-to-Target for Axial Spondyloarthritis
- Treat-to-Target for Systemic Lupus Erythematosus
- Treat-to-Target for Osteoarthritis
- Treat-to-Target for Gout
- 53 Building a Therapeutic Alliance to Enhance Patient Education and Self-Management
- Key Points
- Introduction
- Provider-Patient Communication, Shared Decision-Making, and Patient Education
- Shared Decision-Making
- Factors Affecting Patient Adherence to Treatments
- Culture and Patient Outcomes
- Health Literacy and Patient Education and Self-Management
- Designing Patient Self-Management Programs
- Development of Arthritis Self-Management Programs: Content and Delivery Mode
- Technology and Arthritis Patient Self-Management
- Evidence for the Effectiveness of Self-Management Education Programs
- Team Care, Team Roles, and Approaches to Management
- Public Health Approaches to Patient Education in Arthritis
- Summary
- 54 Health Literacy a
- Key Points
- Background
- Development of Definitions and Conceptual Models of Health Literacy
- Approaches and Instruments to Measure Health Literacy
- Research on Health Literacy and Outcomes
- Addressing Patients’ Health Literacy Needs
- Future Steps in Health Literacy Research
- Summary
- 55 Principles of Rehabilitation: Physical and Occupational Therapy
- Key Points
- Rehabilitation and its role in people with disability caused by rheumatic diseases
- Rehabilitation adopts a biopsychosocial approach to patients and their needs
- Patient-centered care is a central tenet of rehabilitation
- Education of patients and caregivers is important to facilitate self-management and adherence to treatment recommendations
- Adherence to an individualized structured exercise program is fundamental to self-management
- Patients should be encouraged and supported to maintain or increase their general physical activity levels
- Aids, adaptive devices, and environmental modifications can maximize functional independence
- Joint protection and energy conservation are important to minimize symptoms
- Occupational rehabilitation is important for patients of working age
- Regular monitoring and follow-up are important
- 56 Multidisciplinary Approaches to Managing Chronic Pain in Arthritis
- Key Points
- Introduction
- Prevalence of Pain in Musculoskeletal and Rheumatologic Conditions
- Measurement of Pain
- Psychological Factors and Pain
- Psychological Factors Associated With Outcome
- Interventions
- Physical Activity for the Relief and Self-Management of Pain
- Lifestyle Management of Rheumatologic Pain
- Joint Protection Programs
- Arthritis Self-Management Programs
- Splinting for the Painful Hand
- Sleep
- Activity Pacing
- Relaxation
- Work
- Patient Education and E-Health
- Novel Interventions for Pain Relief
- Graded Motor Imagery Program
- Visual Illusions
- Conclusion
- 57 Placebo, Nocebo, Caring, and Healing in Rheumatology
- Key Points
- Introduction
- Biological Mechanisms
- Conclusions
- 58 Integrative Medicine
- Key Points
- Overview and Use
- Communication and Resources
- Types of Complementary Medicine Approaches
- Mind-Body Techniques
- Acupuncture
- Herbal Medicine
- Diet
- 59 Indications for and Long-Term Complications of Total Hip and Knee Arthroplasty
- Key Points
- Introduction
- Indications
- Clinical Presentation
- Contraindications to Total Joint Arthroplasty
- Age and Total Joint Arthroplasty
- Body Mass Index and Total Joint Arthroplasty
- Outcomes
- Complications
- Nonorthopedic Complications
- Orthopedic Complications
- Impact of Body Mass Index on Complications
- Impact of Age on Complications
- Conclusion
- 60 Outcomes and Perioperative Management of Patients With Inflammatory Arthritis and Systemic Lupus Erythematosus Undergoing Total Joint Arthroplasty
- Key Points
- Introduction
- Outcomes and Adverse Events
- Spondyloarthritis
- SLE
- Perioperative Management
- Perioperative Management of Comorbid Medical Conditions
- Venous Thromboembolism
- Antiphospholipid Syndrome
- Management of Antirheumatic Therapy
- Chronic Glucocorticoid Therapy
- Prevention of Postoperative Infection
- Conclusion
- 61 Medication Management During Preconception, Pregnancy, and Lactation
- Key Points
- Introduction
- Pregnancy
- Rheumatic Diseases and Pregnancy
- Aspirin and Other Nonsteroidal Antiinflammatory Drugs
- Glucocorticoids
- Antimalarials
- Sulfasalazine
- Immunosuppressive Agents
- Azathioprine
- Cyclosporine
- Mycophenolate Mofetil
- Tacrolimus
- Methotrexate
- Leflunomide
- Cyclophosphamide
- Intravenous Immunoglobulin
- Tumor Necrosis Factor-α Blockade and Inhibitors
- Rituximab, Belimumab, and Other Biologic Agents
- Small Molecules
- Inadvertent Teratogenic Medication Exposure
- Paternal Medications Before and After Conception
- Conclusion
- 62 Telemedicine in Rheumatology
- Key Points
- Definition, History, and Evolution of Telerheumatology
- Telemedicine Visits and Other Telehealth Modalities
- Synchronous Telehealth
- Asynchronous Telehealth
- Telemedicine Technical Aspects and Digital Literacy
- A Successful Telemedicine Visit Workflow
- Appropriateness of Telemedicine Visits in Rheumatology
- Telemedicine Advantages
- Telemedicine Disadvantages
- Effectiveness of Telemedicine in Rheumatology
- Telemedicine Practice: Legal Requirements and Reimbursement Policies
- Future Directions
- 63 Multimorbidity
- Key Points
- Introducing the Concept of Multimorbidity
- Assessment and Screening of Multimorbidity
- Impact of Multimorbidity
- Mortality
- Disease-Related Outcomes
- Prevalence of Multimorbidity
- Impact of Distinct Morbid Conditions
- Cancer
- Depression
- Respiratory Diseases
- Other Important Morbid Conditions
- Taking Care of Multimorbid Rheumatic Patients
- Conclusion
- 64 Infections in Rheumatoid Arthritis: Biologic Therapy and JAK Inhibitors
- Key Points
- Rheumatoid Arthritis and Burden of Infection
- Prednisone
- Biologic Therapies and Risk for Infection
- Tumor Necrosis Factor Antagonists and Risk for Infection
- Opportunistic Infections With Anti–Tumor Necrosis Factor Therapy
- Abatacept, Rituximab, Tocilizumab, and Anakinra
- Risk for Serious Bacterial and Opportunistic Infections
- JAK Inhibitors
- Prevention of Infection in Patients Treated With Biologics or JAK Inhibitors: Screening and Vaccination
- Intracellular Pathogens
- Conclusion
- Acknowledgment
- 65 Vaccinations in Patients With Autoimmune Rheumatic Diseases
- Key Points
- Rationale for vaccinations in autoimmune rheumatic diseases
- Vaccination concerns
- Types of vaccinations
- Recommended vaccinations
- Pneumococcal vaccination
- Human papillomavirus (HPV) vaccination
- Zoster vaccination
- Respiratory syncytial virus (RSV) vaccination
- COVID-19 vaccination
- Diphtheria, pertussis, and tetanus vaccinations
- Hepatitis A virus vaccination
- Hepatitis B virus vaccination
- Effects of immunomodulatory therapies on vaccination responses
- Immunosuppressants
- Biological DMARDS
- B Small Molecules
- 66 Pharmacologic Pain Management
- Key Points
- Introduction
- Opioid mechanisms
- The evidence
- Patient selection and medication management
- Prescription drug monitoring plans
- Informed consent
- Dosing
- Drug monitoring
- Adverse drug effects
- Driving and opioids
- Older adults and chronically Ill patients
- Acute-on-chronic pain
- Dual-action opioids
- Nonopioid Medications for Chronic Pain
- Tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and calcium channel blockers (gabapentinoids)
- Topical analgesics
- Cannabinoids
- Low-dose naltrexone
- 67 Nonsteroidal Antiinflammatory Drugs
- Key Points
- Introduction
- Mechanism of action
- Cyclooxygenase isozyme selectivity
- Pharmacokinetics and drug interactions
- Clinical efficacy
- Adverse effects
- Gastrointestinal
- Cardiovascular
- Renal
- Respiratory
- Hepatic
- Rational selection of nonsteroidal antiinflammatory drug therapy
- 68 Systemic Glucocorticoids in Rheumatology
- Key Points
- Nomenclature and Pharmacology
- Dosing
- Bioequivalence and Bioavailability
- Metabolism and Drug Interactions
- Clearance and Dose Timing
- Mechanisms of Glucocorticoid Action
- Efficacy
- Efficacy in Systemic Connective Tissue Disorders and Vasculitis
- Efficacy in Polymyalgia Rheumatica and Large-Vessel Vasculitis
- Adverse Effects
- Bone and Muscle
- Cardiovascular
- Dermatologic and Appearance
- Gastrointestinal
- Infectious Diseases
- Metabolic and Endocrine
- Neuropsychiatric
- Ophthalmologic
- Use in Pregnancy
- Practical Recommendations
- Perioperative and Stress-Dose Considerations
- Glucocorticoids in Children
- Glucocorticoid Withdrawal Regimens
- 69 Methotrexate
- Key Points
- Introduction
- Pharmacology
- Mechanism of Action
- Efficacy in Rheumatoid Arthritis
- Efficacy Compared With Other Disease-Modifying Antirheumatic Drugs
- Efficacy in Combination With Other Disease-Modifying Antirheumatic Drugs
- Effect of Methotrexate on Structural Damage
- Long-Term Studies
- Predictors of Response to Methotrexate
- Effect on Mortality
- Adverse Effects
- Hepatic Toxicity
- Pulmonary Toxicity
- Vaccination
- Other Adverse Effects
- Teratogenicity
- Folic Acid Supplementation
- Methotrexate Use in Rheumatoid Arthritis: Recommendations
- Methotrexate in Other Rheumatic Diseases ( Table 69.3 )
- Juvenile Idiopathic Arthritis
- Other Rheumatic Diseases
- Conclusions
- 70 Conventional Synthetic Disease-Modifying Antirheumatic Drugs Including Leflunomide
- Key points
- Introduction
- Sulfasalazine
- Pharmacology
- Mode of action
- Efficacy
- Safety and tolerability
- Fertility and breastfeeding
- Dosage, interactions, cautions, and monitoring
- Leflunomide
- Pharmacology
- Mode of action
- Efficacy in rheumatoid arthritis
- Monotherapy
- Combination therapy
- Combination therapy with biologic agents
- Efficacy in other rheumatic diseases
- Safety and tolerability
- Toxicity treatment
- Fertility and breastfeeding
- Dosing, interactions, cautions, and monitoring
- Hydroxychloroquine
- Pharmacology
- Mode of action
- Efficacy
- Additional csDMARDs
- 71 Immunosuppressive Agents: Cyclosporine, Cyclophosphamide, Azathioprine, Mycophenolate Mofetil, Tacrolimus, Avacopan, and Voclosporin
- Key Points
- Introduction
- Mechanisms of Action
- Cyclophosphamide
- Cyclosporine
- Mycophenolate Mofetil
- Tacrolimus
- Pharmacokinetics
- Azathioprine
- Cyclophosphamide
- Cyclosporine
- Mycophenolate Mofetil
- Tacrolimus
- Efficacy, Toxicity, and Therapeutic Use
- Cyclophosphamide
- Cyclosporine
- Mycophenolate Mofetil
- Tacrolimus
- Avacopan
- Efficacy, Toxicity, and Therapeutic Use
- Voclosporin
- Efficacy, Toxicity, and Therapeutic Use
- 72 Kinase Inhibitors and Other Targeted Synthetic Agents
- Key Points
- Introduction
- Tyrosine kinases
- Tyrosine kinase inhibitors
- JAK inhibitors for rheumatoid arthritis
- JAK inhibitors for other rheumatological indications
- Other kinase inhibitors
- C Biologic Agents
- 73 Overview of Biologic Agents
- Key Points
- Introduction
- Antibodies and the Humoral Immune Response
- Antibody Structure
- Structural Characterization of Approved Antibody Therapeutics
- Mechanisms of Action
- Placental Transfer of Biological Drugs
- Immunogenicity
- Specific MoA of Biological Drugs: Relating Structure to Function
- Cell Depletion: B Cells as an Example
- Targeting Cell–Cell Interactions
- Future Directions
- Alternative Structures
- Using Multiple Antibodies and Bispecific Molecules
- 74 Interleukin-1 Inhibitors
- Key Points
- Interleukin-1 Cytokines
- Interleukin-1 Plays a Critical Role in Inflammation
- Regulation of Interleukin-1β Maturation by the Inflammasome
- Therapeutic Inhibitors of Interleukin-1 in Rheumatic Diseases
- Rheumatoid Arthritis
- Ankylosing Spondylitis
- Psoriatic Arthritis
- Systemic Lupus Erythematosus
- Osteoarthritis
- Crystal-Induced Arthritis
- Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still Disease
- Interleukin-1 Inhibition for Periodic Fever Syndromes
- Other Autoinflammatory Disorders
- General Comments on Available Interleukin-1 Inhibitors
- 75 Interleukin-6 Inhibitors
- Key Points
- Discovery and action of IL-6
- Role of IL-6 in the pathogenesis of autoimmune and inflammatory diseases
- Large vessel vasculitis and polymyalgia rheumatica
- Still’s disease
- Systemic sclerosis
- Castleman disease
- Neuromyelitis optica
- Drug targeting on IL-6 and IL-6 receptor signaling
- Clinical efficacy and safety of IL-6 inhibitors in autoimmune and inflammatory diseases
- Rheumatoid arthritis: safety
- Large-vessel vasculitis (Takayasu and giant cell arteritis)
- Still disease
- Systemic sclerosis
- Castleman disease
- Neuromyelitis Optica
- Polymyalgia rheumatica
- COVID-19
- 76 Interleukin-17, Interleukin-12, and Interleukin-23 Inhibitors
- Key Points
- Potential cytokine targets in rheumatic diseases
- Interleukin-17
- Interleukin-17 in rheumatic disease
- Clinical trials of IL-17 blockade
- Interleukin-23
- Interleukin-12 and Interleukin-23 in rheumatic diseases
- Clinical trials of IL-12/IL-23 blockade
- Significant points
- Conclusion
- 77 Tumor Necrosis Factor Inhibitors
- Key Points
- Introduction
- Mechanism of Action
- Biologic Effects
- Clinical Use of TNF Inhibitors in RA, AS, and PsA
- Ankylosing Spondylitis
- Psoriatic Arthritis
- Approved Indications and Practical Use
- Adalimumab
- Pharmacology
- Indications and Use
- Adalimumab in RA Pivotal Trials
- Adalimumab in PsA and AS
- Etanercept
- Pharmacology
- Indications and Use
- Etanercept in RA Pivotal Trials
- Etanercept in PsA and AS
- Infliximab
- Pharmacology
- Indications and Dosing
- Clinical Efficacy of Infliximab in RA
- Infliximab in PsA and AS
- Certolizumab Pegol (Cimzia)
- Pharmacology
- Indications and Dosing
- Clinical Efficacy of Certolizumab Pegol in RA
- Certolizumab Pegol in PsA and AS
- Golimumab
- Pharmacology
- Indications and Dosing
- Clinical Efficacy of Golimumab in RA
- Golimumab in PsA and AS
- Dose Reduction or Discontinuation of TNF Inhibitors
- Tapering Trials in PsA and Axial SpA
- Immunogenicity
- Nonresponse to TNF Inhibitors
- Nonresponse to TNF Inhibitors in PsA and Axial SpA
- TNF Inhibitors in Different Clinical Situations
- TNF Inhibitors in Children
- TNF Inhibitors in Elderly Patients
- TNF Inhibitors in Patients With ILD
- TNF Inhibitors in Patients With Heart Failure
- TNF Inhibitors in Patients With Hepatitis B Infection
- TNF Inhibitors in Patients With Atherosclerotic Heart Disease
- TNF Inhibitors in Patients With Previous Malignancies
- TNF Inhibitors and Elective Surgery
- TNF Inhibitors and Fertility, Pregnancy, and Lactation
- TNF Inhibitors and Vaccination
- Other Indications in Which TNF Inhibitors Have Been Used
- Granulomatous Diseases
- Antineutrophil Cytoplasmic Cntibody (ANCA)–Associated Vasculitis
- Giant Cell Arteritis (GCA)
- Polymyalgia Rheumatica
- Sarcoidosis
- Pyoderma Gangrenosum
- Hidradenitis Suppurativa
- Takayasu Arteritis
- Noninfectious Uveitis
- Behçet’s Disease
- Adverse Events with TNF Inhibitors
- Infusion Reactions
- Injection Site Reactions
- Infections
- Tuberculosis
- Hepatitis B and C
- Herpes Zoster
- Other Opportunistic Infections
- Malignancy
- TNF Inhibitor Induced Lupus (ATIL) and Vasculitis
- Neurological Side Effects
- Congestive Heart Failure (CHF)
- Cytopenias
- Hepatotoxicity
- Cutaneous Side Effects
- Unusual Side Effects
- Monitoring
- Conclusion
- 78 Inhibitors of T-cell Costimulation
- Key Points
- Rationale for targeting T cells in rheumatoid arthritis
- Costimulatory signal in T-cell activation
- Abatacept
- Clinical efficacy
- Safety
- Safety of abatacept in routine clinical practice
- Real world effectiveness and safety
- Biologic effects
- Summary of the efficacy and safety of abatacept
- New costimulatory inhibitors
- Conclusions
- 79 Inhibitors of B Cells
- Key Points
- Introduction
- Roles of B Cells in Rheumatic and Musculoskeletal Diseases
- Targeting CD20
- Rituximab
- Rituximab Biosimilars
- Other Type 1 and 2 Anti-CD20 Molecules
- Efficacy for Rheumatoid Arthritis
- Radiographic Outcomes
- Outcome of Repeat Cycles
- Effect of Rituximab Dose
- Retreatment of Nonresponse
- Concomitant Conventional Synthetic Disease-Modifying Antirheumatic Drugs
- Factors Predicting Response to Rituximab
- Rituximab: Use in Connective Tissue Diseases
- ANCA-Associated Vasculitis
- Systemic Lupus Erythematosus
- Sjogren Disease
- Safety of Rituximab
- Screening Before Therapy
- Infusion Reactions
- Infections
- Low Immunoglobulin Levels Before and After Rituximab
- Vaccination Responses and Immunization Following Rituximab
- Progressive Multifocal Leukoencephalopathy
- Immunogenicity
- Rituximab in Chronic Lung Disease
- Malignancy
- Obinutuzumab
- Inhibition of B-Cell Survival Factors
- Efficacy and Safety of Belimumab in Systemic Lupus Erythematosus
- Future B-Cell Inhibition Approaches
- Summary
- 80 Interferons and Interferon Inhibitors
- Key Points
- The role of interferon in systemic lupus erythematosus
- Interferon biology
- Clinical trials with interferon inhibitors
- Early development of anifrolumab
- Late development of anifrolumab
- The anifrolumab long term extension
- Interferon and the kidney
- Additional analyses of the anifrolumab dataset
- Litifilimab
- Early development of litifilimab
- The approaches to inhibit IFN-1 are eclectic
- Summary
- 81 Biosimilars in Rheumatology
- Key Points
- Definitions
- Biomimics
- “Second-Generation” Biopharmaceuticals
- Development of Biosimilars
- Demonstration of Biosimilarity
- Biosimilars for Inflammatory Diseases and Osteoporosis
- Biosimilars in Development
- Immunogenicity
- Extrapolation of Indications
- Interchangeability
- Nomenclature
- Cost
- 82 Emerging Therapeutic Targets
- Key Points
- B-lineage cells
- CD19 CAR T cells
- Bispecific T-cell engagers
- Inebilizumab
- CD38
- B cell growth factors
- Neonatal Fc receptor
- T cells
- Anticytokine therapies
- Interferon alpha
- IL-17 axis
- IL-4/IL-13 axis
- Signaling pathways
- TYK2
- BTK inhibition
- Toll-like receptors
- Targeting complement
- Miscellaneous targets
- Lymphocyte migration
- Manipulating gene expression
- Vagal nerve stimulation
- Summary
- D Experimental Therapies in Man
- 83 Treatment of Rheumatic Diseases by CAR T-Cells and Other Cellular Therapies
- Engineering of Therapeutic Cells
- The Procedure of Autologous CAR T-Cell Therapy
- Unique Features of CAR T-Cells
- Adverse Effects of CAR T-Cells
- Clinical Outcomes of CAR T-Cells in Autoimmune Disease
- Immune Reset
- Challenges of CAR T-cell Therapy
- Other Forms of Cell Therapy in Autoimmune Disease
- Regulatory T Cells and CAR T Regs
- Mesenchymal Stem Cells
- Summary
- 84 Induction of Tolerance in Relation to Rheumatic Disease
- Key Points
- Introduction
- Immunological Tolerance and Autoimmune Diseases
- The Rheumatic Diseases
- Defining Autoimmune Disease
- Autoimmune Rheumatic Diseases
- Focused Immunotherapy in Autoimmune Diseases
- Inducing Immune Tolerance in Autoimmune Diseases
- Stage of Disease
- Identity of Autoantigens for ASIT
- MHC-Disease Association
- Tolerance-Induction Strategies
- Tolerance-Inducing Strategies for the Rheumatic Diseases
- Future Potential for Tolerance-Inducing Strategies in Rheumatic Diseases
- Section 6 Regional and Widespread Pain
- 85 Neck Pain
- Key Points
- Introduction
- Epidemiology
- Risk Factors
- Pathogenesis of Neck Pain
- Clinical Assessment
- Clinical Examination
- Clinical Examination
- General Examination
- Neurologic Examination
- Neck Movement
- Cervical Nerve Root Compression
- Clinical Features
- Clinical Examination
- Investigations
- Blood Tests
- Investigations Targeting Pain
- Treatment of Neck Pain
- Nonspecific Treatments
- Specific Treatments
- Treatment—Cervical Nerve Root Compression
- Treatment Modalities
- Whiplash
- Biomechanics
- Pathology
- Imaging
- Natural History
- Treatment of Acute Whiplash Injury
- Treatment of Chronic Whiplash
- Conclusion
- 86 Low Back Pain
- Key Points
- Epidemiology
- Impact
- Risk Factors
- Clinical Evaluation
- History
- Physical Examination
- Investigations
- Clinical Laboratory Tests
- Electrodiagnostic Studies
- Concerning Causes of Low Back Pain ( Box 86.3 )
- Cauda Equina Compression
- Abdominal Aortic Aneurysm
- Infections
- Herpetic Neuralgia
- Neoplasms
- Rheumatologic Causes
- Primary Bone Disorders
- Referred Pain
- Mechanical Causes of Low Back Pain
- Spondylolysis and Spondylolisthesis
- Intervertebral Disc Disorder and Vertebrogenic Low Back Pain
- Zygapophyseal (Facet) Joint Syndrome
- Lumbar Spinal Stenosis
- Management of Lumbar Spine Disorders
- Conservative Approaches
- Oral Drug Therapy
- Injection Therapy
- Complementary/Integrative Therapies
- Surgical Treatment
- Neuromodulation
- 87 The Shoulder
- Key Points
- Functional Anatomy
- The Glenohumeral Joint
- Acromioclavicular Joint
- Scapulothoracic Joint
- Sternoclavicular Joint
- Bursae
- Nerve and Blood Supply
- History and Physical Examination
- Examination
- Differential Diagnoses
- Rotator Cuff Tears, Tendinopathy, and Impingement
- Clinical Features
- Investigations
- Management
- Calcific Tendonitis
- Clinical Features
- Investigations
- Management
- Biceps Pathology and SLAP Tears
- Clinical Features
- Investigations
- Management
- Frozen Shoulder
- Clinical Features
- Investigations
- Management
- Glenohumeral Joint Instability
- Clinical Features
- Investigations
- Management
- Glenohumeral Arthritis
- Clinical Features
- Investigations
- Management
- Acromioclavicular Joint Instability
- Clinical Features
- Investigations
- Management
- Acromioclavicular Arthritis
- Clinical Features
- Investigations
- Management
- Lateral Clavicular Osteolysis
- Scapular Winging
- Scapulothoracic Crepitus
- Sternoclavicular Disorders
- 88 The Elbow
- Key Points
- Anatomy of the Elbow
- Clinical Evaluation
- Investigations
- Elbow Disorders
- Bone and Joint Conditions
- 89 The Wrist and Hand
- Key Points
- Introduction
- Clinical Evaluation
- Physical Examination
- Resting Posture
- Swelling and Deformity
- Differential Diagnosis of Joint Swelling
- Differential Diagnosis of Wrist and Hand Pain
- Specific Disorders of the Wrist and Hand
- Trigger Finger or Thumb (Stenosing Digital Tenosynovitis)
- de Quervain Syndrome
- Intersection Syndrome
- Ganglions of the Wrist and Hand
- Carpal Tunnel Syndrome
- Dupuytren Disease
- 90 The Hip
- Key Points
- Functional Anatomy
- Joint Capsule
- Hip Musculature
- Bursae
- Blood Supply
- Clinical Evaluation
- History
- Physical Examination
- Radiographic Evaluation
- Other Imaging
- Role of Imaging in Clinical Practice
- Specific Hip Disorders
- Hip Dysplasia
- Femoroacetabular Impingement
- Periarticular Soft Tissue Problems
- 91 The Knee
- Key Points
- Structure of the knee joint
- Soft tissue anatomy
- Neurovascular supply
- Menisci
- Clinical evaluation of a patient with knee symptoms
- Examination
- Imaging
- Specific disorders of the knee
- Early childhood
- Adolescence
- Adults
- Disorders occurring across the age spectrum from adolescence
- 92 The Ankle and Foot
- Key Points
- Introduction
- Epidemiology of foot and ankle problems
- Anatomy of the ankle and foot
- Ankle
- Foot
- Examination of the foot and ankle
- Imaging
- Other assessments
- Local ankle and foot problems
- Impingement syndromes
- Achilles tendinopathy
- Tibialis posterior tendon dysfunction and acquired adult flatfoot
- Flatfeet (pes planus) and high-arched feet (pes cavus)
- Nerve entrapments
- Heel pain
- Midfoot pain
- Forefoot pain
- Foot problems secondary to systemic conditions
- Psoriatic arthritis and seronegative diseases
- Juvenile idiopathic arthritis
- Osteoarthritis
- Connective tissue diseases
- Crystal arthropathies
- Hypermobility syndrome
- 93 The Temporomandibular Joint
- Key Points
- Epidemiology, Etiology, and Classification
- Functional Anatomy
- Clinical Features
- Management
- Nonsurgical Management
- Surgical Management
- Relationship to Other Chronic Pain Disorders
- Section 7 Rheumatoid Arthritis
- 94 Classification and Epidemiology of Rheumatoid Arthritis
- Key Points
- Classification of Rheumatoid Arthritis
- Disease Occurrence
- Incidence
- Prevalence
- Geographic Variation
- Time Trends
- Environmental Factors
- Nutrition
- Medications
- Infectious Agents
- Socioeconomic Status and Occupation
- Urban and Industrialized Environments
- Host Factors
- Race
- Birth Weight
- 95 Clinical Features of Rheumatoid Arthritis
- Key Points
- Introduction
- Clinical Evaluation
- Examination and Clinical Features of Specific Joints
- Diagnosis
- Natural History
- Patterns of Onset
- Patterns of Progression
- Clinical Course
- Prognosis
- 96 Extraarticular Features of Rheumatoid Arthritis
- Key Points
- Introduction
- Skin disease
- Hematologic abnormalities
- Felty syndrome
- Hepatic abnormalities
- Cardiac disease
- Ocular involvement
- Neurologic impairment
- Muscular involvement
- Renal abnormalities
- Amyloidosis
- Rheumatoid vasculitis
- Acknowledgment
- 97 Common Comorbidities in Rheumatoid Arthritis
- Key Points
- Introduction
- Measurement of comorbidity
- Cardiovascular disease and cardiovascular risk factors
- Venous thromboembolism
- Malignancy
- Metabolic disease
- Osteoporosis and osteopenia
- Mental health
- Fibromyalgia and central pain sensitization
- Frequent infections
- Gastrointestinal disease
- Chronic pulmonary disease
- Chronic kidney disease
- Screening and management of comorbidities in patients with rheumatoid arthritis
- Conclusion
- 98 Rheumatoid Arthritis-Related Lung Disease
- Key Points
- Introduction
- Interstitial Lung Disease
- Pathobiology
- Evaluation
- Treatment
- Airway Diseases and Bronchiectasis
- Pathobiology
- Evaluation
- Chest Imaging
- Pulmonary Function Tests
- Treatment
- Pleural Disease
- Pathobiology
- Clinical Presentation
- Evaluation
- Treatment
- Pulmonary Nodules
- Pathobiology
- Evaluation
- HRCT Imaging
- FDG-PET
- Lung Biopsy
- Treatment
- Conclusion
- 99 Imaging of Rheumatoid Arthritis
- Key Points
- Introduction
- Approach to Imaging and General Imaging Features
- Imaging Modalities
- Arthrography
- Ultrasonography
- Computed Tomography
- Magnetic Resonance Imaging
- Emerging Imaging Modalities
- Final Points
- 100 Genetics of Rheumatoid Arthritis
- Key Points
- Strength of Genetic Contribution
- The Role of Major Histocompatibility Complex Genes
- History
- Refining the Amino Acid Sites Driving Rheumatoid Arthritis Susceptibility
- The Biologic Function of HLA-DRB1 Risk Alleles
- Genetic Association Between Human Leukocyte Antigen Alleles and Anticyclic Citrullinated Peptide-Positive and -Negative Rheumatoid Arthritis
- Major Histocompatibility Complex: Disease Susceptibility or Severity?
- The Role of Non-Major Histocompatibility Complex Genes
- Candidate Gene Association Studies in Rheumatoid Arthritis
- Genome-Wide Association Studies in Rheumatoid Arthritis
- Ethnic Differences in Rheumatoid Arthritis Susceptibility
- Insight Into the Pathogenesis of Rheumatoid Arthritis From Nonmajor Histocompatibility Complex Genetic Studies
- Gene and Environment Interactions
- Conclusion
- Summary
- 101 Animal Models of Rheumatoid Arthritis
- Key Points
- Introduction
- Mechanisms of Induction of Experimental Arthritis
- Response to Nonspecific Immunologic Stimuli
- Components of Infectious Agents
- Immune Complex-Induced Arthritis
- Anti-citrullinated Protein Antibodies (ACPAs) and Arthritis Models
- Gene Manipulation and Transgenic Models
- Standardization of Antigen-Emulsion Preparations for the Induction of Rheumatic Arthritis
- The Three “Rs”
- Conclusions
- 102 Autoantibodies in Rheumatoid Arthritis
- Key Points
- Introduction
- Rheumatoid factor and anti-citrullinated protein antibodies
- Anti-citrullinated protein antibodies
- Relevance of RF and ACPA determination for diagnosis and prognosis of RA
- IgA isotypes of RF and ACPA
- Antibodies to other posttranslational modifications
- Antibodies to carbamylated antigens
- Antibodies to acetylated antigens
- Potential added diagnostic value of Anti-CarP and AAPA
- Antibodies to unmodified antigens
- Anti-RA33 antibodies
- Novel candidate antigens
- Autoantibodies in the pathogenesis of RA
- The role of the mucosa
- The impact of immunoglobulin glycosylation on arthritis
- The AMPA-producing B cell response
- Pathogenic roles of ACPAs and RFs
- 103 Pathogenesis and Pathology of Rheumatoid Arthritis
- Key Points
- Introduction
- Normal Synovium
- Synovium in Rheumatoid Arthritis
- Pannus
- Histologic Subtypes of Rheumatoid Arthritis Synovium
- Mechanisms of Chronic Synovitis in Rheumatoid Arthritis
- Cellular Immunology of Seropositive Rheumatoid Arthritis and Genetic Risk Loci
- Cells of Rheumatoid Synovium
- Macrophages
- Synovial Fibroblasts
- Molecular Mediators in Rheumatoid Synovium
- Tumor Necrosis Factor
- The Tumor Necrosis Factor Superfamily
- Interleukin-1
- Interleukin-6
- Interleukin-18 and Other IL-1 Family Members
- Type I and Type II Interferons (Interferon-α, β, and γ)
- Interleukin-10
- Interleukin-17
- Transforming Growth Factor-β
- Other Cytokines
- Chemokines
- Arachidonic Acid Metabolites
- Ligands for Toll-Like Receptors
- Complement and Immune Complexes
- Angiogenesis in Rheumatoid Arthritis
- Vasculogenesis
- Regulatory Networks in Synovial Angiogenesis
- Perspectives on Targeting Angiogenesis
- Joint Destruction
- Matrix Metalloproteinases
- Collagenases
- Stromelysins
- Other Matrix Metalloproteinases and Related Enzymes
- The Role of Matrix Metalloproteinases in Inflammation
- Protease Inhibitors
- Cysteine and Serine Proteases
- Bone Destruction
- Seronegative Rheumatoid Arthritis
- Embracing the Complexity of Inflammation in Rheumatoid Arthritis
- Conclusion
- Acknowledgment
- 104 Preclinical Rheumatoid Arthritis
- Key Points
- Introduction and overview of rheumatoid arthritis development
- The pathophysiology of rheumatoid arthritis during pre-RA
- Systemic inflammation
- Cellular features
- Genes and environment
- Emerging: the mucosal origin hypothesis of RA development
- An overall model of the pathophysiology of pre-RA
- Caveats to the model of RA development
- Prediction of future rheumatoid arthritis
- Prevention of rheumatoid arthritis
- Clinical care recommendations for individuals in the at-risk state
- Conclusion
- 105 Assessment of the Patient With Rheumatoid Arthritis and the Measurement of Outcomes
- Key Points
- Introduction
- 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis
- Disease Process (“Disease Activity”) and Its Consequence (“Disease Outcome”)
- Evaluation Versus Prognostication
- Individual Measures Versus Composite Indices
- Definition and Evaluation of Treatment Targets in Clinical Practice
- Assessment Strategies in Clinical Trials
- Instruments for Assessing Disease Activity
- Core Sets of Disease Activity Variables
- Composite Indices of Disease Activity
- Improvement Criteria
- Remission Criteria
- Instruments for Assessing Physical Function
- Instruments for Assessing Structural Progression
- Other Imaging Modalities
- Other Instruments: Fatigue, Work Productivity, and Comorbidity
- Conclusion
- 106 Management of Rheumatoid Arthritis in csDMARD-Naïve Patients
- Key Points
- Introduction
- Early Diagnosis and Treatment
- Treating to Target
- Disease-Modifying Antirheumatic Drug (DMARD) Therapy
- Glucocorticoids
- csDMARD Strategies—Initial monotherapy Versus Combination Therapy
- Biologic/Targeted Synthetic DMARD Induction Strategies
- Biologic DMARD Induction Followed by Tapering
- Treatment Stratification in Early RA
- Non-DMARD and Nonpharmacological Management
- 107 Management of Rheumatoid Arthritis in Patients With Prior Exposure to Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs)
- Key Points
- Introduction
- Therapeutic overview
- Guiding principles of treatment
- Adjusting therapy to achieve targets
- Comparative efficacy of targeted DMARDs (tDMARDs)
- Treatment withdrawal
- General safety monitoring of DMARD therapies
- Nonclass-specific adverse events with targeted therapies
- Potential class-specific adverse events with tDMARDs
- Fertility and pregnancy
- Comorbid disease
- Cardiovascular disease
- Interstitial lung disease
- Conclusions
- 108 Multidisciplinary Nonpharmacologic Approach to Rheumatoid Arthritis
- Key Points
- Introduction
- Self-Management and Patient Education
- Exercise Therapy
- Hands-On Techniques and Physical Modalities
- Orthoses, Insoles, and Shoes
- Assistive Devices
- Nutrition
- Interventions Preventing Job Loss and Work Disability
- Multidisciplinary Team Care
- Digital Health Interventions
- Infection-Related Rheumatic Diseases
- A Infectious Arthritis
- 109 Bacterial Native Joint Arthritis
- Key Points
- Introduction
- Epidemiology and Origins of Bacterial Arthritis
- Bacterial Pathogens
- Clinical Presentation
- Differential Diagnosis
- Laboratory and Radiologic Diagnosis
- Management of Bacterial Arthritis
- Techniques for Lavage/Drainage
- Resection, Arthrodesis, or Amputation
- Systemic Antibiotic Treatment
- Total Duration of Antibiotic Therapy
- Supportive Therapy and the Need for Future Research
- Outcomes of Therapy
- Conclusion
- 110 Mycobacterial, Brucellar, Fungal, and Parasitic Arthritis
- Key Points
- Introduction
- Tuberculous Arthritis
- Pathophysiology
- Musculoskeletal Manifestations
- Spondylitis (Pott Disease)
- Peripheral Arthritis
- Osteomyelitis
- ReA (Poncet Disease)
- Soft Tissue Abscess and Panniculitis
- Diagnosis
- Imaging
- Spondylitis
- Peripheral Arthritis
- Osteomyelitis
- Treatment
- Prevention
- Leprosy and Other Mycobacterial Infections
- Microbiology
- Clinical Characteristics
- Diagnosis
- Treatment
- Prevention
- Brucellosis
- Microbiology
- Clinical Manifestations
- Diagnosis
- Treatment
- Prevention
- Fungal Musculoskeletal Infections
- Histoplasmosis
- Blastomycosis
- Paracoccidioidomycosis
- Coccidioidomycosis
- Cryptococcosis
- Aspergillosis
- Sporotrichosis
- Parasitic Arthritis
- Protozoans
- Diagnosis
- Helminths
- Cestodes
- Diagnosis
- Nematodes
- Diagnosis
- Trematodes
- Diagnosis
- Treatment
- 111 Viral Arthritis
- Key Points
- Introduction
- Human Immunodeficiency Virus
- Principles of Management of Inflammatory Diseases in the Setting of HIV
- Special Situations in Evaluating and Treating Patients With HIV and Rheumatic Disorders
- Parvovirus B19
- Clinical Manifestations
- Laboratory Investigation
- Treatment
- Hepatitis B Virus
- Clinical Manifestations
- Hepatitis C Virus
- Clinical Manifestations
- Chikungunya and Other Alphaviruses
- Clinical Manifestations
- Laboratory Investigation
- Treatment
- Human T-cell Lymphotropic Virus Type I
- Other Viruses
- B Other Infection-Related Disease
- 112 Lyme and Other Tickborne Diseases
- Key Points
- History
- Epidemiology
- Etiologic Agent
- Pathogenesis
- Clinical Manifestations
- Skin
- Nervous System
- Cardiac System
- Joints
- Diagnosis
- Other Tickborne Diseases
- Differential Diagnosis
- Treatment
- Post-Lyme Disease Symptoms
- Prevention
- 113 Acute Rheumatic Fever
- Key Points
- Introduction
- Epidemiology
- Rheumatic Fever Risk Factors
- Environmental Factors
- Host Factors
- Pathophysiology
- Molecular Mimicry and Epitope Spreading
- Humoral Immune response
- Cellular Immune Response
- Pathology
- Myocarditis
- Endocarditis
- Pericarditis
- Arthritis
- Chorea
- Clinical Manifestations
- Arthritis
- Carditis
- Sydenham Chorea
- Erythema Marginatum
- Subcutaneous Nodules
- Other Clinical Features
- Investigations
- Throat Cultures
- Rapid Antigen Detection Test
- Streptococcal Antibody Tests
- Acute-Phase Reactants
- Other Laboratory Findings
- Echocardiography
- Diagnosis
- Treatment
- Primary Prevention: GAS Vaccine
- Primary Prevention (Pharyngitis Treatment)
- Acute Rheumatic Fever
- Sydenham Chorea
- Secondary Prevention
- Endocarditis Prophylaxis
- Emergency Valve Procedure
- 114 Reactive Arthritis
- Key Points
- Introduction
- Epidemiology
- Pathogenesis
- Chlamydia-induced Reactive Arthritis (CiReA)
- Factors Affecting Host Resilience to Infection
- Clinical Features
- Investigations
- Treatment
- Prognosis
- COVID-19-Related Arthritis
- Conclusion
- Section 9 Spondyloarthritis and Psoriatic Arthritis
- 115 Classification and Epidemiology of Spondyloarthritis
- Key Points
- The historical concept of spondyloarthritis
- The evolution of axial spondyloarthritis
- Diagnosis and classification of axial spondyloarthritis
- Classification of peripheral spondyloarthritis
- Prevalence of spondyloarthritis
- Impact of gender
- Conclusion
- 116 Enthesopathies
- Key Points
- Introduction
- History
- Anatomy and Pathology
- Histopathologic Features and Cellular Basis for Enthesitis
- Enthesitis and the Pathogenesis of Spondyloarthritis
- Enthesitis and Osteitis
- Enthesitis and Anatomically Similar Structures
- An Enthesitis-Based Model of Spondyloarthritis
- Sites of Enthesitis
- Symptoms and Signs
- Differential Diagnosis
- Imaging
- Magnetic Resonance Imaging
- Conventional Radiography
- Ultrasonography
- Clinical Scores for Enthesitis Assessment
- Management
- First-Line Therapy
- Disease-Modifying Therapy for Enthesitis
- Conclusions
- 117 Inflammatory Back Pain
- Key Points
- Introduction
- Inflammatory Back Pain Criteria
- Inflammatory Back Pain in the Population
- Patient Referral Strategies
- Inflammatory Back Pain in Diagnosis
- 118 Clinical Features of Axial Spondyloarthritis
- Key Points
- Introduction
- Clinical features
- Arthritis
- Enthesitis
- Dactylitis
- Extra-musculoskeletal manifestations
- Other
- Physical examination findings
- Laboratory and imaging investigations
- Diagnosis and classification
- Clinical assessment of axSpA
- Burden of disease and prognosis
- 119 Pathogenesis and Pathophysiology of Axial Spondyloarthritis
- Key Points
- Introduction
- Axial spondyloarthritis: an autoinflammatory disease with ties to genetics, the microbiome, and environmental factors
- Key inflammatory mediators in spondyloarthritis
- Histopathology and new bone formation
- 120 Genetics of Axial Spondyloarthritis
- Key Points
- Genetic epidemiology of radiographic spondyloarthritis
- Major histocompatibility complex genes
- HLA-B27 and its subtypes
- Other major histocompatibility complex genes
- Non-major histocompatibility complex (non-MHC) genes
- Genetics of acute anterior uveitis
- Radiographic spondyloarthritis in East Asians
- Radiographic spondyloarthritis in Africans
- Summary and conclusions
- 121 Animal Models of Spondyloarthritis
- Key Points
- Introduction
- HLA-B27 transgenic animals
- HLA-B27 transgenic mice
- HLA-B27 transgenic rats
- TNF overexpression models
- Human TNF-transgenic mice
- TNF overexpression through deletion in the AU-rich elements
- tmTNF transgenic mice
- IL23/IL17 pathway
- Beta-glucan-induced disease in SKG mice
- Mechanical loading
- Selective A20 deficiency
- Microbiome
- Conclusion
- 122 Imaging in Spondyloarthritis
- Key Points
- Introduction
- Imaging of the sacroiliac joints
- Importance of imaging of the sacroiliac joints
- Conventional radiology
- Computed Tomography
- Scintigraphy
- Magnetic Resonance Imaging
- Differential diagnoses for involvement of the sacroiliac joint
- Imaging of the spine
- Conventional radiographs
- Computed Tomography
- Magnetic resonance imaging
- Definition of a positive magnetic resonance imaging of the spine
- Differential diagnoses for involvement of the spine
- Cauda equina syndrome
- Extravertebral manifestations of axial spondyloarthritis
- Future directions
- 123 Management of Axial Spondyloarthritis
- Key Points
- Historical Perspective
- Current Perspectives
- Assessment of the Efficacy of Treatment of Axial Spondyloarthritis
- Pooled Indices
- Specific Clinical and Laboratory Markers
- Physical Therapy
- Pharmacologic Therapy
- Glucocorticoids
- Conventional Synthetic Disease-Modifying Antirheumatic Drugs
- Targeted Synthetic Disease-Modifying Antirheumatic Drugs
- Biologic Disease-Modifying Antirheumatic Drugs ( Table 123.3 )
- Tumor Necrosis Factor-α–Blocking Agents
- Management of ExtraMusculoskeletal Manifestations
- Surgical Intervention in Ankylosing Spondylitis
- Spinal Surgery
- 124 Classification and Epidemiology of Psoriatic Arthritis
- Key Points
- Introduction
- Classification
- Epidemiology
- Risk factors for PsA among patients with psoriasis
- Comorbidities among patients with PsA
- Conclusions
- 125 Clinical Features of Psoriatic Arthritis
- Key Points
- Introduction
- History, epidemiology, and criteria
- Epidemiology
- Principles of the diagnosis of psoriatic arthritis
- Classification criteria used in psoriatic arthritis trials
- Key clinical features: skin and joints
- Transition from psoriasis to psoriatic arthritis
- Peripheral joint involvement
- Other musculoskeletal features
- Enthesitis
- Axial involvement
- Other extraarticular features
- Evaluation and follow-up
- Prognosis
- Comorbidities
- Investigations
- Imaging investigations
- Other imaging modalities of the peripheral joints
- 126 Extraarticular Manifestations and Comorbidities in Psoriatic Arthritis
- Key Points
- Introduction
- Extraarticular Manifestations
- Inflammatory Bowel Disease
- Ocular Manifestations
- Comorbidities
- Cardiovascular Risk Factors: Metabolic Syndrome, Obesity, Diabetes Mellitus, Dyslipidemia, and Hypertension
- Malignancy
- Liver Disease
- Kidney Disease
- Infections
- Osteoporosis
- Fibromyalgia and Central Sensitization
- Depression and Anxiety
- Gout
- 127 Etiology and Pathogenesis of Psoriatic Arthritis
- Key Points
- Introduction
- Genetic Factors
- Epigenetics
- Environmental Factors
- Trauma, Severity of Psoriasis, Obesity, and Diet
- Cells, Cytokines, and Pathways Involved in Skin and Joint Tissue Inflammation
- Tissue-Resident Memory T Cells and Local Immune Memory
- Immunopathology
- Psoriatic Plaque
- Nail Disease
- Synovium
- Enthesis
- Dactylitis
- Links Between Skin and Musculoskeletal Inflammation
- Pathologic Cartilage Resorption and Altered Bone Remodeling
- Altered Bone Remodeling
- Conclusion
- 128 Animal Models of Psoriatic Arthritis
- Key Points
- Animal Model Strategies and Concepts
- Challenges in the Development of Animal Models for Psoriatic Disease
- Animal Models of PsA
- Humanized Mouse Models
- Spontaneous Models of PsA
- Transgenic Approaches Toward PsA Models
- Induced Models of PsA
- Lessons Learned and Future Perspectives
- 129 Management of Psoriatic Arthritis
- Key Points
- Introduction
- Assessment of Disease Activity
- Comparison of Recommendations/Guidelines
- NSAIDs and Glucocorticoids
- Conventional Synthetic DMARDs
- Methotrexate
- Sulfasalazine
- Leflunomide
- Cyclosporin
- Biologic DMARD
- TNF Inhibitors
- IL-17A Inhibitors
- IL-12 and IL-12/23 Inhibitors
- CTLA4
- tsDMARDs
- JAK Inhibitors
- PDE4 Inhibitors
- Emerging Therapeutics
- Treat-To-Target
- Precision Medicine
- Difficult-To-Treat PsA
- Non-pharmacological Therapies
- Conclusion
- Volume Two
- Section 10 Systemic Lupus Erythematosus and Related Diseases
- 130 Epidemiology and Classification of Systemic Lupus Erythematosus
- Key Points
- Introduction
- Classification of Systemic Lupus Erythematosus for Clinical Studies and Trials
- Systemic Lupus Erythematosus Heterogeneity and Subtypes
- Descriptive Epidemiology of Systemic Lupus Erythematosus
- Sex
- Age
- Risk Factors for SLE
- Hormonal/Reproductive Factors
- Lifestyle Factors: Cigarette Smoking, Alcohol Consumption, Dietary Intake, and Obesity
- Environmental Exposures
- Vitamin D and Ultraviolet Light
- Psychosocial Stressors
- Infections and Immunizations
- Epidemiology of Adverse Outcomes Among Patients with Systemic Lupus Erythematosus
- Social Determinants of Health
- Conclusions
- 131 Preclinical Features of Systemic Lupus Erythematosus
- Key Points
- Introduction
- Importance of Understanding and Identifying Preclinical Lupus
- Healthy Individuals With Antinuclear Autoantibodies
- Clinical and Serologic Features of Healthy Individuals Who Transition to Systemic Lupus Erythematosus
- Risk Factors for Transition in Relatives of Patients With Systemic Lupus Erythematosus
- Environmental Exposures and Life Experiences in the Preclinical Period That Associate With Future SLE Development
- Clinical Manifestations and Transition of Patients with Incomplete, Potential, or Latent Lupus
- Transition of Patients With Undifferentiated Connective Tissue Disease to Systemic Lupus Erythematosus
- Development of Systemic Lupus Erythematosus in Patients With Another Autoimmune Disease
- Conclusions
- 132 Clinical Features of Systemic Lupus Erythematosus
- Key Points
- Introduction
- Clinical Features
- General Manifestations
- Cutaneous Manifestations
- Musculoskeletal Features
- Renal Manifestations
- Neuropsychiatric Manifestations
- Gastrointestinal Involvement
- Lymphatic and Hematologic Involvement
- Pulmonary involvement
- Cardiac Manifestations of Systemic Lupus Erythematosus
- Accelerated atherosclerosis
- Endocrine
- Eye, Ear, nose, throat
- Malignancies
- Infections
- 133 Genetics of Systemic Lupus Erythematosus
- Key Points
- Introduction
- Female Dominance of Lupus
- Polygenic Lupus
- Genetic Mechanisms[Q9] Affected by Lupus Variants
- From Genetic Association to Causal Variant(s) and Affected Gene(s)
- Pathway Analyses Generated From Systemic Lupus Erythematosus Loci
- Monogenic Lupus
- Somatic Mutations
- Complexity and Genomics Beyond DNA Sequence Variation
- Mendelian Randomization Paragraphs
- Organ-Specific Genetics
- Environmental Contributions
- Epstein-Barr Virus Gene Products Interacting With Systemic Lupus Erythematosus Loci
- Closing Perspective
- 134 Immunopathology of Systemic Lupus Erythematosus
- Key Points
- Introduction
- Pathology
- Cutaneous Immunopathology
- Vascular Immunopathology
- Immunopathology of Lymphoid Organs
- Renal Immunopathology
- Central Nervous System Immunopathology
- Cardiac Immunopathology
- Pulmonary Immunopathology
- Properties of Immune Complexes
- Antibodies and Antigens
- Critical Properties of Immune Complexes
- Pathogenic Mechanisms
- Biology of Immune Complex Handling
- Role of Complement in Immune Complex Handling
- Receptors for the FC Region of ImmunoglobulinG
- Complement and Fcγ Receptor Function: Targets for Treatment
- 135 Animal Models of Systemic Lupus Erythematosus
- Key Points
- Introduction
- Spontaneous mouse models
- MRL/lpr and MRL/gld
- BXSB and TLR7 expressing strains
- Induced models of SLE
- Pristane induced SLE
- bm12 GVHD mouse model
- Immunizations with autoantigens
- Engineered mouse models
- Clearance of apoptotic cell debris
- Detection and degradation of nucleic acids
- Activation and survival of lymphocytes
- Murine models and lupus therapies
- Conclusions
- 136 Autoantibodies in Systemic Lupus Erythematosus
- Key Points
- Introduction
- Antinuclear antibodies
- Fluorescent ANA assay
- Techniques for detecting ANA specificity
- Antinuclear and anticytoplasmic autoantibodies
- “Antiphospholipid” autoantibodies
- Cell membrane antigens
- Autoantibodies as the initial manifestation of autoimmunity
- Mechanisms of autoantibody production in lupus
- How are lupus autoantigens selected?
- How do autoantibodies cause disease?
- 137 Pathogenesis of Systemic Lupus Erythematosus
- Key Points
- Genetic SUSCEPTIBILITY and Gender and Environmental Triggering factors
- Innate Immune Responses
- Neutrophils and Neutrophil Extracellular Traps (NETs)
- Dendritic Cells and Other Antigen-Presenting Cells
- Adaptive Immune Responses
- T Cells and Regulation of the Immune Response
- Local Factors Involved in Lupus Pathogenesis
- Concluding Remarks
- 138 Pathogenesis of Lupus Nephritis
- Key Points
- Epidemiology
- Genetics
- Immune-Mediated Mechanisms Underlying Pathogenesis of Lupus Nephritis
- Intrarenal Immune Complex Deposition Drives Local Immune Responses and Kidney Damage
- Innate and Adaptive Immune Cell Contributions to Lupus Nephritis
- Cellular Signaling Across Immune Cells
- Renal Cell Injury
- Linking the Pathogenesis of Lupus Nephritis to ISN/RPS Histological Classification
- Conclusion
- 139 Drug-Induced Lupus
- Key Points
- Introduction
- Etiology
- Drug Induced Cutaneous Lupus Erythematosus
- Epidemiology of DIL
- Age and Gender Contributions to Drug-Induced and Idiopathic Lupus
- Genetic Predisposition
- Pathogenesis
- Drug Transformation
- Epigenetic Dysregulation
- Role of DNA Methylation in T Cells
- T Cells, DNA Methylation, and Idiopathic Lupus
- T Cells, DNA Methylation, and the Environment
- Role of NETosis and the Innate Immune System
- Other Mechanisms of Autoreactivity
- Recombinant Biologic Agents
- Clinical Aspects
- Autoantibodies and Laboratory Findings
- Reversibility and Management
- Summary
- Acknowledgment
- 140 Assessing Systemic Lupus Erythematosus Disease Activity: Measures and Outcomes
- Key Points
- Introduction
- Global Disease Activity Indices
- Modified Versions of SLEDAI
- Additional Disease Activity Indices
- Organ-Specific Instruments
- British Isles Lupus Assessment Group Disease Activity Index
- Renal Outcome Measures
- Cutaneous Outcome Measures
- Disease State Measures
- Measurement of Improvement
- Measurement of Low Disease Activity State and Remission
- Measurement of Flares
- Damage
- Special Populations
- Pregnancy
- Miscellaneous
- Future Directions
- Conclusions
- 141 The Management of Nonrenal/Noncentral Nervous System Lupus
- Key Points
- Introduction
- Recommended Assessment and Monitoring of Systemic Lupus Erythematosus Patients With Nonrenal/Noncentral Nervous System Manifestations
- Management of Musculoskeletal Manifestations
- Arthritis
- Avascular Necrosis
- Myositis
- Management of Cutaneous Manifestations
- General Nonpharmacological Measures
- Topical Treatment
- Systemic Therapy
- Biologic Therapies and Experimental Drugs
- Hematological Involvement
- Management of Cardiopulmonary Manifestations
- Management of Other Nonrenal/Noncentral Nervous System Manifestations
- Treat to Target in Systemic Lupus Erythematosus
- 142 Management of Neuropsychiatric Lupus
- Key Points
- Etiology of Neuropsychiatric Systemic Lupus Erythematosus
- Clinical Manifestations of Selected Neuropsychiatric Events
- Headache
- Psychosis, Mood Disorders, and Anxiety
- Cerebrovascular Disease
- Seizures
- Demyelination, Transverse Myelopathy, and Chorea
- Peripheral Nervous System Disease
- Acute Confusional State
- Neurocognitive Disorders
- Diagnosis of Neuropsychiatric Systemic Lupus Erythematosus
- Neuroimaging in Neuropsychiatric Systemic Lupus Erythematosus
- Treatment of Neuropsychiatric Events in Patients With Systemic Lupus Erythematosus
- Ischemic-Mediated Injury
- Inflammation-Mediated Injury
- Supportive and Nonpharmacological Care
- Outcome of Selected Neuropsychiatric Events
- Acknowledgment
- 143 Management of Renal Lupus
- Key Points
- Introduction
- Therapeutic Agents in Lupus Nephritis
- Mycophenolate Mofetil/Mycophenolic Acid
- Calcineurin Inhibitors
- Biologic Agents
- B-cell Depleting Agents
- Treatment Strategy and Recommendations
- Proliferative Lupus Nephritis
- Class V Lupus Nephropathy
- Monitoring and Targets of Therapy
- Kidney Protective Treatment and Management of Chronic Kidney Disease
- End-Stage Kidney Disease and Kidney Replacement Modalities
- 144 Systemic Lupus Erythematosus in Pregnant Patients and Neonatal Lupus
- Key Points
- Introduction
- Fertility in Patients with SLE
- Pre-pregnancy Evaluation and Counseling
- Stratifying Pregnancy Risks Associated with SLE
- Stratifying Pregnancy Risks Associated with Comorbidities
- Medication Use in Pregnancy
- Maternal and Fetal Complications During Pregnancy
- Distinguishing Changes of Normal Pregnancy from Lupus Flares
- Lupus Nephritis and Preeclampsia
- Antiphospholipid Antibodies
- Neonatal Lupus
- Pregnancy and Systemic Lupus Erythematosus Management
- Labor and Delivery
- Lactation
- Postpartum
- 145 Sjögren Disease
- Key Points
- History
- Epidemiology
- Glandular Pathology
- Clinical Features
- Extraglandular Manifestations
- Systemic Autoimmunity
- Association with Other Autoimmune Diseases
- Lymphoproliferative Disease
- Natural History
- Classification Criteria
- Diagnostic Evaluation
- Ophthalmologic Examination
- Major Salivary Glands
- Labial or Parotid Gland Biopsy
- Assessment of Disease Activity
- Differential Diagnosis
- Pathogenesis
- Genetic Susceptibility
- Environmental Factors
- Role of the Target Tissue
- Immune Pathways
- Lymphomagenesis
- Management
- Extraglandular Manifestations
- Lymphoma
- 146 Antiphospholipid Syndrome: Pathogenesis, Diagnosis, and Management
- Key Points
- Antiphospholipid syndrome: definition and history
- Epidemiology
- Pathogenesis
- Mechanisms of thrombosis
- Mechanisms of pregnancy loss
- Clinical features
- Venous thrombosis
- Arterial thrombosis
- Pregnancy complications
- OAPS classification criteria concerns
- Nervous system abnormalities
- Cardiac valve abnormalities
- Skin manifestations
- Thrombocytopenia and hemolytic anemia
- Renal manifestations
- Catastrophic antiphospholipid syndrome
- Laboratory diagnosis
- Novel serologic assays for antiphospholipid syndrome
- Seronegative APS
- Importance of scoring systems in APS
- Management
- Pregnancy management
- General pregnancy care in women with obstetric antiphospholipid syndrome (OAPS)
- Pharmacologic management of antiphospholipid syndrome during pregnancy
- Recurrent early (preembryonic or embryonic) miscarriage
- Fetal death or prior early delivery due to severe preeclampsia or placental insufficiency
- Antiphospholipid syndrome with thrombosis
- Postpartum period
- Management of other manifestations of antiphospholipid syndrome
- Alternative therapies for refractory and difficult cases
- Hydroxychloroquine
- Statins
- Rituximab
- Complement inhibition
- Future treatments
- Section 11 Systemic Sclerosis
- 147 Classification and Epidemiology of Systemic Sclerosis
- Key Points
- Introduction
- Disease Classification
- Disease Diagnosis and the Very Early Disease Subset
- Epidemiology
- Disease Risk Factors
- Influence of Age, Sex, Ethnicity
- Sex
- Ethnicity
- Survival
- Survival Prognosis Factors
- Summary and Conclusion
- 148 Clinical and Serologic Features of Systemic Sclerosis
- Key Points
- Introduction
- Diagnosis and Classification
- Clinical Features
- Musculoskeletal
- Gastrointestinal Tract
- Heart
- Lungs
- Renal Scleroderma
- Digital Vasculopathy
- Neurologic Manifestations of Systemic Sclerosis
- Calcinosis
- Sexual Dysfunction
- Psychological and Social Impact of Systemic Sclerosis
- Serologic Features of Systemic Sclerosis
- Autoimmune Serology
- Autoantibodies in Overlap Systemic Sclerosis
- Other Serologic Markers in Systemic Sclerosis
- Risk Stratification
- Functional Autoantibodies in SSc and Individual Complications
- Conclusions
- 149 Etiology and Pathogenesis of Systemic Sclerosis
- Key Points
- Introduction
- Etiology
- Female Sex Bias in Systemic Sclerosis
- Genetic Studies in Systemic Sclerosis
- Single Cell–Level Analyses Reveal Complexity of Cell Phenotypes in Systemic Sclerosis
- Transcriptional Regulation of Gene Expression
- Infectious Agents in Systemic Sclerosis
- Environmental Exposure, Drugs, and Radiation
- The Pathologic Features of Systemic Sclerosis
- Vascular Pathology
- Tissue Fibrosis
- Organ-Specific Pathologic Findings in Systemic Sclerosis
- Pathogenesis: A Triad of Immunity, Vascular Injury, and Fibrosis
- Inflammation and Immunity
- Vascular Injury and Vasculopathy in Systemic Sclerosis
- Tissue Fibrosis
- Growth Factors and Chemokines That Trigger and Sustain Fibrosis
- Animal Models of Systemic Sclerosis
- Heritable Animal Models of Scleroderma
- Inducible Animal Models of Scleroderma
- Immunologically Induced Mouse Models of Systemic Sclerosis
- 150 Outcome Measures in Systemic Sclerosis
- Key Points
- Introduction
- Measuring Disease Activity, Damage, and Severity in Scleroderma
- Disease Activity in Scleroderma
- Assessment of Disease Damage
- Assessment of Disease Severity
- Outcome Measures in Scleroderma
- Measuring Skin Disease in Scleroderma
- Measuring Musculoskeletal Involvement in Scleroderma
- Measuring Cardiopulmonary Disease in Scleroderma
- Measuring Gastrointestinal Tract Disease in Scleroderma
- Measuring Vascular Disease in Scleroderma: Raynaud Phenomenon and Digital Ulcers
- Measuring Physical Function and Health-Related Quality of Life
- Composite Endpoints
- Biomarkers for Scleroderma
- Conclusion and Authors’ Perspective on Outcome Measure Development in Systemic Sclerosis
- 151 Management of Systemic Sclerosis
- Key Points
- Introduction
- Principles of Effective Management
- Clinical Trials in Systemic Sclerosis
- Disease-Modifying Therapies for Systemic Sclerosis
- Organ-Based Assessment and Treatments
- Raynaud Phenomenon
- Musculoskeletal Complications
- Skin Thickening
- Other Skin Manifestations
- Gastrointestinal Complications
- Lung Disease
- Renal Scleroderma
- Macrovascular Disease
- Cardiac Disease
- Summary
- 152 Emerging Therapies for Systemic Sclerosis
- Key Points
- Introduction
- Skin fibrosis as an outcome for clinical trials
- Change in clinical trial design for emerging therapies in systemic sclerosis
- Development of targeted therapies for systemic sclerosis
- Randomized clinical trials from 2020 to 2025 to identify emerging therapies in systemic sclerosis
- Interstitial lung disease as the primary outcome
- Skin as the primary outcome
- Composite response index in system sclerosis as the primary outcome
- Pulmonary hypertension as the primary outcome
- Gastrointestinal symptoms as the primary outcome
- Level of evidence for emerging therapies
- Summary
- 153 Raynaud Phenomenon
- Key Points
- History
- Nomenclature
- Epidemiology and Etiology
- Pathophysiology
- Neural Abnormalities and Mechanisms
- Vascular Abnormalities and Mechanisms
- Intravascular Abnormalities and Mechanisms
- Clinical Features
- Investigations
- Confirming Raynaud phenomenon
- Investigations for Secondary Causes
- Management
- General Measures
- Drug Treatment
- Surgery
- Conclusion
- 154 Localized Scleroderma and Scleroderma-Like Syndromes
- Key Points
- Localized Scleroderma (Morphea)
- Circumscribed Morphea
- Linear Morphea
- Generalized Morphea
- Pansclerotic Morphea
- Mixed Morphea
- Section 12 Inflammatory Muscle Disease
- 155 Clinical Features, Classification, and Epidemiology of Inflammatory Muscle Disease
- Key Points
- Epidemiology
- Incidence and Prevalence by Age, Race, and Sex
- Environmental Factors
- Genetic Factors
- Clinical Features
- Constitutional
- Skeletal Muscle
- Skin
- Calcinosis
- Joints
- Lung
- Heart
- Gastrointestinal Tract
- Peripheral Vascular System
- Kidney
- Differential Diagnosis
- Other Inflammatory Myopathies
- Malignancy and Myositis
- Investigations
- Serum Muscle Enzymes
- Electromyography
- Muscle Biopsy
- Magnetic Resonance Imaging
- Skin
- Serum Autoantibodies
- Overview of the Natural History and Disease Prognosis
- Prognostic Considerations
- Disability
- 156 Etiology and Pathogenesis of Inflammatory Muscle Disease (Myositis)
- Key Points
- Introduction
- Muscle Biology and Physiology
- Muscle Development and Regeneration
- Etiology
- Genetic Factors
- Environmental Factors
- Infections
- Ultraviolet Light and Vitamin D Deficiency
- Drugs
- Smoking
- Malignancy
- Pathogenesis
- Muscle Histopathologic Features
- Immunopathologic Features
- Cytokines and Chemokines
- Immune Mechanisms and Muscle Function
- Humoral Mechanisms
- Inclusion Body Myositis
- Conclusion
- 157 Clinical Significance of Autoantibodies in Inflammatory Muscle Disease
- Key Points
- Introduction
- Myositis-Associated Autoantibodies
- Anti-PM-SCL
- Anti-RO/SSA and Anti-LA/SSB
- Anti-KU
- Anti-U1-SNRNP
- Anti-PUF60
- Myositis-Specific Autoantibodies
- Anti-synthetase Antibodies
- Dermatomyositis-Specific Autoantibodies
- Anti-Mi-2
- Anti-MDA5
- Anti-TIF-1γ
- Anti-SAE
- Anti-NXP2
- Inclusion Body Myositis–Associated Antibody
- Immune-Mediated Necrotizing Myopathy–Associated Antibodies
- Anti-HMGCR
- Conclusion
- Acknowledgment
- 158 Management of Inflammatory Muscle Disease
- Key Points
- Introduction
- General management considerations in IIM
- Assessing disease activity and damage
- Overall treatment approach of IIM using immunosuppressive and immunomodulatory agents
- Corticosteroids
- First-line steroid sparing agents commonly used to treat myositis
- Methotrexate
- Azathioprine
- Mycophenolate mofetil
- Second-line steroid sparing agents
- Cyclosporine and tacrolimus
- Rituximab
- Cyclophosphamide
- Janus kinase inhibitors
- Treatment Algorithm based on Myositis Subgroups
- Immune-mediated necrotizing myopathy
- Inclusion body myositis
- Other therapies in idiopathic inflammatory myopathies (excluding IBM)
- Antimalarials
- Adrenocorticotropic Hormone Gel
- Emerging therapies in IIM excluding IBM
- Nonpharmacologic treatments
- Management of extramuscular manifestations
- Cardiac involvement
- Gastrointestinal involvement
- Calcinosis
- Conclusion
- 159 Metabolic, Drug-Induced, and Other Noninflammatory Myopathies
- Key Points
- Metabolic Myopathies
- Glycogen and Glucose Metabolism ( Fig. 159.1 )
- Defects of Glucose and Glycogen Metabolism
- Lipid Metabolism
- Fatty Acid Oxidation Disorders
- Mitochondrial Myopathies
- Myoadenylate Deaminase Deficiency
- Drug- and Toxin-Induced Myopathies
- Statins
- Colchicine
- Hydroxychloroquine
- Glucocorticoids
- Antiretroviral Therapy
- Immune Checkpoint Inhibitors
- Alcohol
- Endocrine Myopathies
- Cushing Syndrome
- Diabetes
- Muscular Dystrophies
- Duchenne Muscular Dystrophy
- Becker Muscular Dystrophy
- Emery-Dreifuss Muscular Dystrophy
- Limb-girdle Muscular Dystrophies
- Myotonic Dystrophy
- Proximal Myotonic Myopathy
- Rippling Muscle Disease
- Myofibrillar Myopathies
- Infectious Myopathies
- Pyomyositis
- Gas Gangrene
- Psoas Abscess
- Influenza
- Human Immunodeficiency Virus
- Parasites
- Acknowledgment
- Section 13 The Vasculitides
- 160 Classification and Epidemiology of Vasculitis
- Key Points
- Introduction
- Definitions, Classification Criteria, and Diagnostic Criteria for Vasculitis
- Background
- American College of Rheumatology 1990 Classification Criteria
- Chapel Hill Consensus Conferences
- European Medicines Agency (EMA) Algorithm
- Criteria for Childhood Vasculitis
- ACR/EULAR 2022 Classification Criteria
- Disease-Specific Classification and Diagnostic Criteria
- Medium-Vessel Vasculitis
- Small-Vessel Vasculitis
- Immune Complex Vasculitis
- Immunoglobulin A Vasculitis (IgAV)
- Urticarial Vasculitis
- Variable Vessel Vasculitis
- Epidemiology of Vasculitis
- Large Vessel Vasculitis
- Takayasu Arteritis
- Medium-Sized Vasculitis
- Kawasaki Disease
- Primary Angiitis of the Central Nervous System (PACNS)
- Small-Vessel Vasculitis
- Granulomatosis with Polyangiitis and Microscopic Polyangiitis
- Eosinophilic Granulomatosis with Polyangiitis
- Immunoglobulin A Vasculitis (IgAV)
- Urticarial Vasculitis
- Behçet Disease
- Future Directions
- 161 Biology and Immunopathogenesis of Vasculitis
- Key Points
- Introduction
- The endothelium
- Endothelial cell activation
- Leukocyte–endothelial cell interaction
- Role of aging in leukocyte–endothelial cell interaction
- Endothelium, coagulation, and inflammation
- Damage and repair: angiogenesis
- Immunopathogenesis of small vessel vasculitis
- Immune complex–mediated small vessel vasculitides
- Antineutrophil cytoplasmic antibody–associated vasculitides
- Immunopathogenesis of major small vessel vasculitides
- Immunopathogenesis of vasculitides of medium- and small-sized arteries
- Polyarteritis Nodosa
- Kawasaki disease
- Immunopathogenesis of large vessel vasculitides
- Giant cell arteritis
- Takayasu arteritis
- Conclusion
- 162 Polyarteritis Nodosa and Cogan Syndrome
- Key Points
- Introduction
- Polyarteritis Nodosa
- Classification
- Epidemiology
- Clinical Features
- Pathology
- Investigations
- Differential Diagnosis
- Management
- Prognosis
- Cogan Syndrome
- Classification
- Epidemiology
- Clinical Features
- Assessment of Disease Activity and Investigations
- Differential Diagnosis
- Management
- Prognosis
- Conclusion
- 163 Antineutrophil Cytoplasm Antibody–Associated Vasculitis
- Key Points
- Definition
- Etiology and Pathogenesis
- Epidemiology
- Classification and Definitions
- Clinical Features
- Investigations and Differential Diagnosis of Antineutrophil Cytoplasm Antibody–Associated Vasculitis
- Pathology
- Clinical Assessment of Vasculitis
- Damage in Vasculitis
- Other Scores
- Assessing Function
- Therapies
- Treatments
- No Treatment
- Topical and Other Treatment of Upper and Lower Airways
- Systemic Glucocorticoid Therapy
- Immunosuppressive Agents
- Other Immunosuppressive Agents
- Outcomes
- 164 Takayasu Arteritis
- Key Points
- History
- Epidemiology
- Clinical Features
- Investigations
- Laboratory Investigations
- Radiographic Studies
- Differential Diagnosis
- Pathology and Pathogenesis
- Management
- Biologic Therapies
- Small Molecule Inhibitors
- Antiplatelet Therapy
- Nonmedical Interventions
- Management of Comorbid Features
- Outcome
- Pregnancy
- 165 Polymyalgia Rheumatica and Giant Cell Arteritis
- Key Points
- Introduction
- Epidemiology, Classification, and Diagnosis
- Relationship Between Polymyalgia Rheumatica and Giant Cell Arteritis
- Pathology
- Pathogenesis
- Role of Infectious Agents
- Immunogenetics
- Innate and Adaptive Immune Mechanisms
- Clinical Findings
- Cranial Symptoms
- Polymyalgia Rheumatica
- Laboratory Findings
- Imaging
- Giant Cell Arteritis
- Differential Diagnosis
- Treatment
- Polymyalgia Rheumatica
- Prognosis
- 166 Behçet’s Disease
- Key Points
- Introduction
- Epidemiology
- Pathogenesis
- Clinical features
- Mucocutaneous features
- Eye involvement
- Musculoskeletal features
- Cardiovascular involvement
- Neurologic involvement
- Gastrointestinal involvement
- Lung involvement
- Others
- Laboratory features
- Disease course and prognosis
- Differential diagnosis
- Management
- 167 Kawasaki Disease
- Key Points
- History
- Epidemiology
- Clinical Features
- Laboratory Assessments
- Pathologic Features
- Etiology and Pathogenesis
- Treatment and Management
- 168 Immunoglobulin A Vasculitis (Henoch–Schönlein Purpura)
- Key Points
- Definition
- Epidemiology
- Classification
- Etiology and Pathogenesis
- Environmental Factors
- Genetic Background
- Clinical Findings
- Cutaneous Involvement
- Joint Involvement
- Gastrointestinal Involvement
- Renal Involvement in Childhood IgAV
- Genitourinary Involvement
- Neurologic Involvement
- Pulmonary Involvement
- Malignancy
- Pregnancy
- Laboratory Features
- Differential Diagnosis
- Treatment
- Treatment of IgA-Associated Nephritis
- Outcome and Prognosis
- 169 Cutaneous Vasculitis and Panniculitis
- Key Points
- Vasculitis
- Clinical Features of Cutaneous Vasculitis
- Evaluation/Workup
- Selected Vasculitic Conditions with Prominent Cutaneous Disease
- Cutaneous Vasculitis in Patients with Rheumatic Diseases
- Cocaine- or levamisole-associated vasculitis/vasculopathy
- Management
- Panniculitis
- Clinical Features
- Differential Diagnosis
- Histopathologic Features
- Selected Subtypes of Panniculitis
- Evaluation/Workup
- Management
- Conclusion
- 170 Cryoglobulinemia and Cryoglobulinemic Vasculitis
- Key Points
- Epidemiology
- Clinical Manifestations
- Skin Manifestations
- Joint and Constitutional Manifestations
- Renal Manifestations
- Nervous Manifestations
- Liver Manifestations
- Lymphoproliferation
- Other Manifestations
- Outcome and Relapses
- Diagnosis and Classification
- Management and Differential Diagnosis
- Pathogenesis
- Therapy
- Monitoring of Response and Circulating B-Cell Clones
- 171 Primary Angiitis of the Central Nervous System
- Key Points
- History
- Case Definition and Criteria
- Epidemiology of PACNS
- Clinical Syndromes of Cerebral Vasculitis
- Pathogenesis
- Pathology
- Laboratory Investigations
- Brain Imaging
- Advanced Intracranial Imaging
- Brain Biopsy Procedure
- Differential Diagnosis
- Reversible Cerebral Vasoconstriction Syndromes
- Fibromuscular Dysplasia
- Cerebral Amyloid Angiitis and Inflammation Subtypes
- Paraneoplastic Angiitis
- Diagnostic Approach
- Treatment and Outcome
- Section 14 Other Systemic Illnesses
- 172 Adult-Onset Still’s Disease
- Key Points
- Introduction
- Epidemiology
- Pathogenesis
- Clinical Presentation
- Fever
- Arthritis
- Rash
- Other Frequent Findings
- Infrequent Findings
- Laboratory Findings
- Classification and Diagnosis
- Management
- First-Line Treatment: Nonsteroidal Anti-inflammatory Drugs and Glucocorticoids
- Second-Line Therapy: Immunosuppressants
- Third-Line Therapy: Biologic Agents
- Tumor Necrosis Factor Inhibitors
- Anakinra
- Canakinumab
- Rilonacept
- Tocilizumab
- JAK Inhibitors
- Special Issues Regarding Treatment
- Macrophage Activation Syndrome
- AA Amyloidosis
- Prognosis and Functional Outcome
- 173 Monogenic Autoinflammatory Diseases
- Key Points
- Introduction
- Interleukin-1 (and Interleukin-18)–Mediated Autoinflammatory Diseases
- Cryopyrin-Associated Periodic Fever Syndromes
- Genetics
- Pathophysiology
- Clinical Features
- Familial Cold Autoinflammatory Syndrome
- Muckle-Wells Syndrome
- Neonatal-Onset Multisystem Inflammatory Disease or Chronic Infantile Neurologic Cutaneous and Arthritis Syndrome
- Recurrent Fever Syndromes
- Phosphomevalonate Kinase Deficiency with Autoinflammation
- TNF-Receptor–Associated Periodic Syndrome
- NLRP1-Associated Autoinflammation with Arthritis and Dyskeratosis
- Monogenic Interleukin-1–Mediated Chronic Recurrent Osteomyelitis Syndromes
- Deficiency of the Intereukin-1 Receptor Antagonist
- Majeed Syndrome
- Loss of Interleukin-1 Receptor Type 1 Sensitivity to Interleukin-1 Receptor Antagonist
- Other Partially Interleukin-1–Mediated Disorders
- Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne Syndrome
- Conditions with High Serum Interleukin-18 Levels and Macrophage Activation Syndrome Predisposition
- Cell Division Control Protein 42–Mediated Autoinflammatory Disease
- Interleukin-18 Pulmonary Alveolar Proteinosis-Macrophage Activation Syndrome
- Treatment of High Interleukin-18 States
- Autoinflammatory Type I Interferonopathies
- The Aicardi-Goutières Syndromes
- STINGopathies: Stimulator of Interferon Genes–Associated Vasculopathy with Onset in Infancy and Coatomer Subunit Alpha [Q52]Syndrome
- Interferon-α/β Receptor 1 Signalopathies
- Other Interferonopathies with Autoantibody-Mediated Disease Manifestations
- Tumor Necrosis Factor and Nuclear Factor kB Signaling–Associated Diseases
- Haploinsufficiency of A20 (Monogenic Form of Behçet Disease)
- Otulin-Related Autoinflammatory Syndrome (ORAS)
- Receptor-Interacting Serine/Threonine-Protein Kinase 1 (RIPK1) Deficiency (Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome)
- Linear Ubiquitination Chain Assembly Complex–Mediated Diseases (HOIL [Heme-Oxidized IRP2 Ubiquitin Ligase 1-Like, Encoded by RBCK1], HOIP [HOIL-1L-Interacting Protein, Encoded by RNF31], SHARPIN [SHANK-Associated RH Domain Interacting Protein])
- Nemo Deleted Exon 5 Autoinflammatory Syndrome and Sterile Alpha Motif Domain Containing 9 Like-Associated Autoinflammatory Disease
- Signaling Modifiers Presenting with Prominent Neutrophilic Vasculitis
- Nonreceptor Tyrosine Kinase–Mediated Autoinflammatory Syndromes
- LYN Gain of Function: Lyn Kinase–Associated Vasculopathy and Liver Fibrosis
- Other Autoinflammatory Diseases
- Deficiency of Interleukin-36 Receptor Antagonist
- Caspase Recruitment Domain Family Member 14-Mediated Psoriasis
- Adaptor Related Protein Complex 1 Subunit Sigma 3-Mediated Pustular Psoriasis (AMPS)
- Laccase Domain Containing 1[Q78]-Mediated Monogenic Still Disease
- VI. Adult-Onset Autoinflammatory Diseases Caused by De Novo Mutations in Hematopoietic Stem or Precursor Cells (NLRP3, NLRC4, TRAPS, VEXAS) and Variable Disease Penetrance Including Monoallelic Expression
- 174 Familial Mediterranean Fever
- Key Points
- Introduction
- Epidemiology
- Clinical Manifestations
- Pathogenesis of FMF
- Genetics of FMF
- Genotype-Phenotype Correlation in FMF
- Diagnosis
- Diagnostic and Classification Criteria
- Treatment of FMF
- Complications - Amyloidosis
- Additional Complications
- Comorbidities
- 175 VEXAS Plus Diseases of Somatic Mutation
- Key Points
- Discovery of VEXAS
- Genetics of Disease
- Disease Pathogenesis
- Epidemiology
- Clinical Features of Disease
- Constitutional Symptoms and Acute Phase Reactants
- Cutaneous Disease
- Hematologic Disease
- Otorhinolaryngologic Disease
- Musculoskeletal Disease
- Respiratory Disease
- Ophthalmologic Disease
- Infectious Disease
- Gastrointestinal and Genitourinary Disease
- Treatment
- Treatment of Systemic Inflammation
- Treatment of Hematologic Manifestations
- Allogeneic Stem Cell Transplantation
- Prophylaxis
- Other Diseases of Somatic Mutations
- Conclusion
- 176 Sarcoidosis
- Key Points
- History
- Epidemiology
- Risk Factors
- Immunopathogenesis
- Step 1: Lymphocytic Alveolitis
- Step 2: Granuloma Formation
- Step 3: Granuloma Resolution
- Diagnostic Investigations
- Laboratory Tests
- Imaging
- Biopsy
- Additional Tests
- Differential Diagnosis
- Clinical Features
- Respiratory Involvement
- Ophthalmologic Involvement
- Cutaneous Involvement
- Cardiac Involvement
- Nervous System Involvement
- Musculoskeletal Involvement
- Other Organ System Involvement
- Childhood Sarcoidosis
- Sarcoidosis Associations with Comorbidities
- Natural History and Prognosis
- Management
- Monitoring of Therapy
- 177 Relapsing Polychondritis
- Key Points
- History
- Epidemiology
- Diagnosis
- Laboratory and imaging findings
- Role of genetic testing and VEXAS syndrome
- Evolving diagnostic paradigm
- Challenges in relapsing polychondritis diagnosis
- Impact of VEXAS on relapsing polychondritis diagnosis
- Limitations of biopsy in relapsing polychondritis diagnosis
- When to consider biopsy
- Clinical manifestations
- Musculoskeletal manifestations
- Inner ear involvement
- Ophthalmologic involvement
- Dermatologic manifestations
- Neurologic system
- Other clinical manifestations
- Overlapping syndromes
- Cogan syndrome
- Pathogenesis
- Clinical features and pathogenesis
- VEXAS and relapsing polychondritis: refining our understanding
- Immunologic studies: limitations and reevaluation
- Evaluations
- Dynamic computed tomography scan for airway disease
- Pulmonary function tests
- Audiology evaluation
- Echocardiogram for valvulitis
- ENT and ophthalmology evaluation
- Targeted studies for specific clinical features
- Management
- 178 The Systemic Amyloidoses
- Key Points
- Introduction
- Amyloidogenesis In Vivo
- Aggregation
- Tissue Deposition
- Tissue Compromise
- Host Responses
- Clinical Epidemiology
- AA Amyloid
- Clinical Features
- Diagnosis
- Treatment
- Aβ 2 -Microglobulin Amyloidosis (Aβ 2 m) (Dialysis-Related Amyloidosis, DRA)
- Clinical Features
- Diagnosis
- Treatment
- AL (Immunoglobulin L-Chain Amyloidosis)
- Epidemiology
- Clinical Features
- Diagnosis
- Treatment
- The Transthyretin Amyloidoses (ATTR)
- Epidemiology
- Clinical Features
- Diagnosis
- Treatment
- Attacking the Deposits
- 179 IgG4-Related Disease
- Key Points
- History and Overview
- Epidemiology
- Clinical Features
- IgG4-Related Type 1 Autoimmune Pancreatitis and Sclerosing Cholangitis
- IgG4-Related Ophthalmic Disease and Sialoadenitis
- IgG4-Related Kidney Disease
- IgG4-Related Respiratory Disease
- IgG4-Related Retroperitoneal Fibrosis (RPF), Periaortitis and Periarteritis
- Other Organ Manifestations
- Clinical Phenotypes
- Laboratory and Image Findings
- Histopathologic Findings
- Radiologic Imaging
- Pathogenesis 67
- Autoantigens
- Innate Immunity
- T-Cell Populations
- B Cells
- Fibrosis
- Diagnosis
- The 2020 Revised Comprehensive Diagnostic (RCD) Criteria for IgG4-RD 85
- The 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria for IgG4-RD
- Differential Diagnosis
- Management
- 180 Immune-Mediated Complications of Checkpoint Inhibitors
- Key Points
- Introduction
- Mechanism of Action/Review of T-Cell Activation
- CTLA-4 Antagonist
- PD-1 Inhibition
- Lag3 Inhibition
- Immune-Related Adverse Events
- Pathophysiology of IrAEs
- Overview of IrAE Toxicity Grades
- Treatment of Rheumatic irAEs
- Targeted therapies
- Anti–TNF–Directed Therapies
- Anti–IL-6–Directed Therapies
- Anti–B-Cell–Directed Therapies
- Anti–T-Cell–Directed Therapies
- Other Targeted Therapies
- Potential Adverse Effects from Targeted Therapies and Glucocorticoids
- Use of Checkpoint Inhibitors in Patients with Preexisting Autoimmune Disease
- Conclusion
- 181 The Epidemiology of Coronavirus Disease 2019 (COVID-19) and Rheumatic Disease
- Key Points
- Introduction
- Risk of COVID-19 Infection in Rheumatic Disease
- Vaccination and Risk of Breakthrough COVID-19 Infection
- Preexposure Prophylaxis
- Acute covid-19-Related Outcomes
- Long COVID
- Multisystem Inflammatory Syndrome in Children and Adults with COVID-19
- The Induction of Autoimmunity and Incident Autoimmune Disease After COVID-19
- Section 15 Osteoarthritis
- 182 Epidemiology and Classification of Osteoarthritis
- Key Points
- Introduction
- Definitions of osteoarthritis
- Radiographic osteoarthritis: Definitions
- Incidence and progression of radiographic osteoarthritis in other joint sites
- Symptomatic osteoarthritis: Definitions
- Mortality rate in osteoarthritis
- Conclusion
- 183 Systemic and Local Risk Factors for Osteoarthritis
- Key Points
- Introduction
- Nonmodifiable Systemic Risk Factors for Knee Osteoarthritis
- Sex/Gender
- Race/Ethnicity
- Genetics
- Anthropometric Measures
- Bone Mineral Density
- Modifiable Systemic Risk Factors for Knee Osteoarthritis
- Nutritional and Dietary Factors
- Occupational Activity
- Nonoccupational Physical Activity
- Smoking
- Social Factors
- Insomnia
- Nonmodifiable Local Risk Factors for Knee Osteoarthritis
- Anthropometric Measures
- Modifiable Local Risk Factors for Knee Osteoarthritis
- Tissue Abnormalities
- Biomechanical Factors
- Hip osteoarthritis
- Joint Morphology
- Hip Biomechanics
- Hand Osteoarthritis
- Hand Osteoarthritis Progression
- Risk Factors for Pain, Functional Limitation, and Disability in Osteoarthritis
- Biomechanical Factors
- Imaging Features Associated with Pain in Osteoarthritis
- 184 Clinical Features of Osteoarthritis
- Key Points
- Introduction
- Definition
- Classification Criteria, Not Diagnostic Criteria
- Symptoms
- Pain
- Joint Deformity and Swelling
- Stiffness
- Mechanical Symptoms
- Signs
- Crepitus
- Joint Swelling
- Observable Deformity
- Gait
- Somatosensory
- Clinical Presentations
- Knees
- Hips
- Hands
- Shoulders
- Feet
- Spine
- Other sites
- Miscellaneous Osteoarthritis Syndromes
- Evaluation
- Patient-Reported Outcome Measures
- Natural History and Mortality
- Conclusion
- 185 Animal Models of Osteoarthritis
- Key Points
- Introduction
- Why Do We Need Osteoarthritis Models?
- How Do We Model Osteoarthritis in Animals?
- What Components of Disease Are Being Modeled?
- Osteoarthritis Models: A Historical Perspective
- How Good Are the Osteoarthritis Models as Models of Human Disease?
- Current Rodent Osteoarthritis Models
- Chemical Induction of Osteoarthritis
- Surgical Induction of Osteoarthritis
- Genetic Modification
- Generation of Genetically Modified Mice
- Animal Model Limitations
- Conclusion
- 186 Pathogenesis and Pathology of Osteoarthritis
- Key Points
- Introduction
- The Normal Joint: Anatomy, Physiology, and Function
- Joint Pathology in Osteoarthritis
- Bone Pathology
- Synovial Pathology
- Meniscal Pathology
- Intraarticular Adipose (Fat Pad) Pathology
- Staging and Grading of Cartilage and Bone Pathology in Osteoarthritis
- Grading of Synovial Membrane Alterations in Osteoarthritis
- Imaging of Joint Pathology in Osteoarthritis
- Pathogenetic Concepts in Osteoarthritis
- Cartilage Matrix Degradation
- Chondrocyte Activation, Differentiation, and Loss
- Disease Risk Factors Inform Pathogenesis
- Aging
- Oxidative Stress and Mitochondrial Dysfunction
- Cellular Senescence and the Senescence-Associated Secretory Phenotype (SASP)
- Autophagy
- Biomechanics and Loading
- Mechanoreceptors
- The Pericellular Matrix (PCM)
- Neuromuscular Function and Proprioception
- Obesity and Metabolic Disease
- Metabolic Derangement and Inflammation
- Other Metabolic/Associated Conditions
- Genetics and Epigenetics
- Epigenetics
- Integration of “Omics” and Single-Cell Methods
- Synovial and Bone Response in OA
- Synovial Inflammation and Pain Sensitization in OA
- Bone Remodeling and Pain in OA
- Conclusion
- Acknowledgment
- 187 Genetics and Epigenetics of Osteoarthritis
- Key Points
- Introduction
- Early Heritability Studies
- Traits and Outcomes Studied in the Genetics of Osteoarthritis
- Twin and Family Studies
- Familial Aggregation Studies
- Familial Disorders Associated with Osteoarthritis
- Candidate Gene Studies in Osteoarthritis
- Genome-Wide Association Studies in Osteoarthritis
- Epigenetics of Osteoarthritis
- Candidate Gene DNA Methylation Studies in Osteoarthritis
- Genome-Wide Epigenetic Studies in Osteoarthritis
- Epigenetics as a Modulator of Genetic Risk
- Conclusions
- 188 Imaging of Osteoarthritis
- Key Points
- Introduction
- Conventional radiography
- Radiographic procedures
- What pathologic features can conventional radiography assess in osteoarthritis?
- Conventional radiography: Quantification and scoring methods
- Magnetic resonance imaging
- What pathologic features can magnetic resonance imaging assess in osteoarthritis?
- Magnetic resonance imaging: Quantification and scoring methods
- Quantitative MRI analysis
- Ultrasound
- What pathologic features can ultrasound assess in osteoarthritis?
- Ultrasound: quantification and scoring methods
- Other imaging modalities
- Positron emission tomography
- Artificial intelligence (AI) and machine learning (ML)
- Considerations for OA imaging in clinical practice
- Considerations for future research in OA imaging
- Summary
- 189 Assessment of the Patient With Osteoarthritis and Measurement of Outcomes
- Key Points
- Introduction
- Fundamental Differences Between Patient Assessment in Clinical Research Versus Routine Clinical Practice
- Selection of Measures for the Evaluation of Patients with Osteoarthritis in Clinical Research
- Core Sets of Measures in OA Research
- Interviewer-Administered Versus Patient-Completed Assessment
- Performance-based Assessment of Impairments and Activity Limitations
- Evaluation of Key Contextual Factors
- Assessing Change in Patient Status
- Interpretation of Measure Change Scores
- Other Explanations for Patient Status Improvement
- Conclusion
- 190 Preclinical and Early Osteoarthritis
- Key Points
- Definition of Preclinical and Early Osteoarthritis
- Evidence for Preclinical and Early Osteoarthritis
- Detection of Preclinical and Early Osteoarthritis
- Progression of Osteoarthritis
- Triggering Mechanisms
- Treatment Paradigms
- Potential Benefits to an Early Diagnosis of Osteoarthritis
- Summary
- 191 Management of Osteoarthritis
- Key Points
- Introduction
- Core Principles in Osteoarthritis Management
- Exercise
- Individualized Treatment
- Multidisciplinary Approach
- Behavioral, Psychosocial, and Physical Interventions
- Orthoses, Braces, and Assistive Devices
- Other behavioral, Psychosocial, and Physical Interventions
- Pharmacologic treatments
- Oral Agents
- Other Oral Agents
- Intraarticular Therapy
- Hyaluronate Preparations
- Surgical Interventions
- Issues Specific to the Management of Hand Osteoarthritis
- Core Principles of Hand Osteoarthritis Management
- Pharmacologic Treatments
- Surgical Interventions
- 192 Emerging Treatments for Osteoarthritis
- Key points
- Introduction
- Symptomatic treatments
- Biologics
- Small Molecules
- Lubricants
- Repurposed Drugs
- Long-Acting Intraarticular Corticosteroids
- Disease-Modifying Osteoarthritis Drugs
- Small Molecules
- Biologics and Synthetic Peptides
- Repurposed Drugs
- Gene Therapy
- H-Vaccine
- Cell Therapies
- Cell-Derived Concentrate
- Research Avenues in Therapeutics
- Section 16 Crystal-Related Arthropathies
- 193 Epidemiology and Classification of Gout
- Key Points
- Historical Perspective
- Westernization and Gout Trends
- Case Definitions and Classification Criteria
- Prevalence of Gout
- Incidence of Gout
- Risk Factors for Hyperuricemia and Gout
- Nonmodifiable Factors: Demographics: Sex, Age, Genetics, and Race and Ethnicity
- Modifiable Factors: Obesity, Insulin Resistance, LifeStyle, and Others
- Environmental and Ambient Exposure
- Key Mediating Mechanisms of Lifestyle Factors: Purine and Insulin Resistance
- Cardiovascular-Metabolic Conditions and Other Disorders
- Racial and Ethnic Disparities and Social Determinants of Health
- 194 Etiology and Pathogenesis of Gout
- Key Points
- Urate Physiology
- Forms of Urate
- Urate Production and Excretion
- Purine Metabolism and Urate Production
- Urate Excretion
- Hyperuricemia
- Classification of Hyperuricemia
- Monosodium Urate crystal Formation
- Articular Protein Interactions with Monosodium Urate Crystals
- The Gout Flare
- NLRP3 Inflammasome Activation
- Other Inflammatory Mediators
- Neutrophil Activation
- Termination of the Gout Flare
- Advanced Gout
- Tophus Formation
- Joint Damage
- The Genetics of Gout
- Transporter Genes
- Metabolic Genes
- Genes Influencing Crystal Formation and Crystal-Triggered Inflammation
- Rare Genetic Disorders
- Summary
- 195 Clinical Features of Gout
- Key Points
- Asymptomatic Hyperuricemia
- Gout Flares
- Intercritical Gout
- Chronic Gouty Arthritis
- 196 Management of Gout and Hyperuricemia
- Key Points
- Treatment of Arthritis and Hyperuricemia in Gout
- Therapeutic Targets for Gout
- Primary Treatment Objectives
- Choice of Drug and Treatment Regimens
- Colchicine and Other Antiinflammatory Drugs for Prophylaxis of Gout
- Interleukin-1 Inhibition for Treatment and Prophylaxis of Gouty Arthritis
- Treatment of Hyperuricemia in Gout
- Indications for Pharmacologic Oral Urate-Lowering Therapy for Gout and Drug Choices
- The Advantages of the “Treat-to-Target” ULT Strategy for Outcomes in Gout
- Treating Hyperuricemia in Severe Gout Refractory to First- and Second-Line Therapy
- Allopurinol
- Febuxostat
- Probenecid
- Pegloticase for Refractory Hyperuricemia in Severe, Chronic Gout
- Recent Developments
- 197 Calcium Pyrophosphate Deposition Disease
- Key Points
- Introduction
- Nomenclature
- Epidemiology
- Clinical Presentation
- Asymptomatic Chondrocalcinosis
- Acute Calcium Pyrophosphate Crystal Arthritis
- Osteoarthritis With Acute Attacks
- Osteoarthritis Without Acute Attacks
- Polyarticular Inflammatory Arthritis
- Neuropathic Arthritis
- Other Forms of Calcium Pyrophosphate Deposition Disease
- Crowned Dens Syndrome
- Extraarticular Calcium Pyrophosphate Deposition Disease Deposits (Tophaceous Calcium Pyrophosphate Deposition Disease)
- Involvement of Other Mineralized Tissues
- Triggers of Acute Attacks of Calcium Pyrophosphate Crystal Arthritis
- Bisphosphonates
- The Postoperative State
- Other Triggers
- Associated Diseases
- Hyperparathyroidism
- Hemochromatosis
- Hypomagnesemia
- Hypophosphatasia
- Gout
- Rheumatoid Arthritis
- Familial Forms of Calcium Pyrophosphate Deposition Disease
- Diagnostic Strategies
- Synovial Fluid Analysis
- Imaging
- Pathology
- Pathogenesis
- Treatment
- Acute Calcium Pyrophosphate Crystal Arthritis ( Box 197.4 )
- Conclusions
- 198 Basic Calcium Phosphate Crystal Deposition Disease
- History
- Intraarticular Basic Calcium Phosphate Crystal Deposition
- Epidemiology
- Articular Calcification
- Clinical Features
- Investigations
- Biochemical
- Synovial or Bursal Fluid
- Identification and Characterization of Basic Calcium Phosphate Crystals
- Differential Diagnosis
- Structure and Function of the Crystals
- Aetiology
- Crystal Formation
- Pathogenesis
- Tumoral Calcinosis
- Basic Calcium Phosphate Crystals and Osteoarthritis
- Cellular Mechanisms of Basic Calcium Phosphate Crystals
- Management
- Tumoral Calcinosis
- Articular Basic Calcium Phosphate Crystals
- Future Therapies
- Conclusion
- Section 17 Pediatric Rheumatology
- 199 Evaluation of Children with Rheumatologic Complaints
- Key Points
- History Taking for the Musculoskeletal System in Children
- Constitutional Features
- Joint Pain
- Joint Swelling and Stiffness
- Examination of the Musculoskeletal System
- Joint Assessment
- Differential Diagnosis
- Septic Arthritis
- Reactive or Postinfectious Arthritis
- Musculoskeletal Syndromes and Benign Limb Pains
- Regional Syndromes: Hip
- Legg-Calvé-Perthes Disease
- Slipped Capital Femoral Epiphyses
- Idiopathic Chondrolysis
- Acetabular Dysplasia, Impingement, and Developmental Dysplasia of the Hip
- Regional Syndromes: Knee
- Chondromalacia Patellae
- Bone Lesions that Mimic Mechanical Knee Disease
- Osgood-Schlatter Disease
- Other Knee Disorders
- Regional Syndromes: Foot
- 200 Classification and Epidemiology of Juvenile Idiopathic Arthritis
- Key Points
- Classification of Childhood Arthritis
- ILAR Classification and Criteria
- Ongoing Challenges
- Descriptive Epidemiology
- Incidence and Prevalence
- Geographic and Ethnic Variation
- Time Trends
- Descriptive Epidemiology of the Different Disease Categories
- Risk Factors
- Genetic Factors
- Course and Prognosis
- Summary
- 201 Clinical Features of Juvenile Idiopathic Arthritis
- Key Points
- Introduction
- General Clinical Features
- Laboratory Investigations
- Imaging
- Clinical Features of Different Categories of Juvenile Idiopathic Arthritis ( Table 201.3 )
- Oligoarthritis, Persistent and Extended
- Polyarthritis
- Psoriatic Arthritis
- Enthesitis-Related Arthritis
- Undifferentiated Arthritis
- Special Problems of Arthritis in Children
- Multidimensional Outcome
- Mortality, Cancer, and Severe Morbidity
- Continuous Activity, Inactivity, and Remission
- Risk Factors for Continuous Activity, Disability, and Damage
- Articular and Skeletal Damage
- Endocrine Damage
- Ophthalmologic Complications and Damage
- Physical Disability
- Quality of Life
- Transition of Care
- 202 Still’s Disease and Macrophage Activation Syndrome
- Definitions and Classifications
- Epidemiology
- Etiology
- Genetic Contribution
- Environmental Factors
- Pathogenesis
- Clinical Manifestations
- Fever
- Rash
- Musculoskeletal Disease
- Laboratory Examinations
- Imaging Features
- Differential Diagnosis
- Complications
- Pathophysiology
- Clinical Features
- Diagnosis
- Management of Macrophage Activation Syndrome
- Chronic Complications
- Pulmonary Complications
- Systemic Juvenile Idiopathic Arthritis Lung Disease Management
- Amyloidosis
- Treatment
- Evidence Supporting the Use of IL-1 and IL-6 Inhibiting Agents in Systemic Juvenile Idiopathic Arthritis
- Course of the Disease and Prognosis
- Patterns of Refractory Disease
- Refractory Systemic Juvenile Idiopathic Arthritis with Predominantly Persistent Arthritis
- Patients with Refractory Systemic Juvenile Idiopathic Arthritis with Predominantly Systemic Features
- Role for Hematopoietic Stem Cell Transplantation in Refractory Systemic Juvenile Idiopathic Arthritis
- 203 Etiology and Pathogenesis of Juvenile Idiopathic Arthritis
- Key Points
- Introduction
- Etiology
- Genetic Factors
- Environmental Factors
- Pathogenesis
- Pathogenesis of Oligo- and Poly-juvenile Idiopathic Arthritis
- Enthesitis-Related Arthritis
- Systemic Juvenile Idiopathic Arthritis
- Conclusion
- 204 Management of Juvenile Idiopathic Arthritis
- Key Points
- Introduction
- Treatment Recommendations for Juvenile Idiopathic Arthritis
- Oligoarthritis
- Polyarthritis Course (Regardless of Onset)
- Systemic Arthritis Without Macrophage Activation Syndrome
- Systemic Juvenile Arthritis With Macrophage Activation Syndrome
- Systemic Juvenile Arthritis and Lung Disease
- Enthesitis-Related Arthritis
- Active Sacroiliac Arthritis
- Juvenile Psoriatic Arthritis
- Uveitis
- Temporomandibular Joint Arthritis
- Nonsteroidal Antiinflammatory Drugs
- Corticosteroids
- Methotrexate
- Other Disease-Modifying Antirheumatic Drugs and Immunosuppressive Medications
- Biologic-Modifying Medications
- Abatacept
- Anti-interleukin-1 Medications
- Anti-interleukin-6 Medications
- Anti-interleukin-17 Medications
- Rituximab
- Janus Kinase Inhibitors
- Stem Cell Transplantation
- Studies of Disease-Modifying Antirheumatic Drug Versus Biologic Combination Therapy for Juvenile Idiopathic Arthritis
- Management of Pain
- Addressing Mental Health
- Rehabilitation
- Management of Growth Delay
- Complementary and Alternative Therapies
- Surgical Interventions
- Synovectomy
- Arthroplasty
- Adjunct Nonsurgical and Surgical Treatment of Temporomandibular Joint Deformities
- Conclusion
- 205 The Juvenile-Onset Spondyloarthropathies
- Key Points
- Classification and Epidemiology
- Clinical Manifestations
- Genetics
- Pathophysiology
- Evaluation of Disease Phenotype and Disease Activity
- Treatment Considerations
- Outcomes
- Conclusions
- 206 Systemic Autoimmune Rheumatic Diseases in Children
- Key Points
- Introduction
- Childhood-Onset Systemic Lupus Erythematosus
- Epidemiology
- Etiopathogenesis
- Clinical Presentation
- Assessment of Disease Activity and Monitoring of Outcome
- Management
- Management and Prevention of Comorbidities
- Clinical Severity and Outcome
- Neonatal Lupus Syndrome
- The Pediatric Inflammatory Myopathies: Juvenile Dermatomyositis
- Epidemiology
- Etiopathogenesis
- Clinical Presentation
- Assessment and Monitoring
- Treatment and Outcome
- Sjögren Disease in Children
- Epidemiology
- Etiopathogenesis
- Clinical Presentation and Features
- Making the Diagnosis
- Management
- Prognosis and Outcomes—More Questions Than Answers
- Pediatric Scleroderma
- Epidemiology
- Etiopathogenesis
- Clinical presentation
- Diagnosis and Management
- Treatment and Outcome
- Prognosis
- Section 18 Metabolic Bone Disease
- 207 Epidemiology and Classification of Osteoporosis
- Key Points
- Introduction
- History
- Definition of Osteoporosis
- Classification of Osteoporosis
- Assessment of Fracture Risk
- Prevalence and Incidence
- Risk Factors
- Impact of Osteoporotic Fracture
- The Relationship Between Bone Mineral Density and Fracture
- Fracture Epidemiology
- Hip Fracture
- Vertebral Fracture
- Distal Forearm Fracture
- Prior Fracture and the Risk of Subsequent Fracture
- Economic Burden of Fracture
- Implications for Prevention
- Secondary Prevention: Treating Those Who Have Already Had a Fracture
- Primary Prevention: Starting Treatment in Individuals at High Fracture Risk
- Future Projections
- Conclusion
- 208 Clinical Evaluation and Clinical Features of Osteoporosis
- Key Points
- Osteoporosis: Definition and Diagnosis
- Clinical Evaluation
- Bone Health Optimization Before Elective Orthopedic Surgery
- History
- History of a Patient on Therapy
- Physical Examination
- Investigations
- Vertebral Fracture Assessment
- Trabecular Bone Score
- Plain Radiography
- Repeat Dual-Energy X-Ray Absorptiometry
- Risk Algorithms
- Bone Turnover Markers
- Laboratory Studies
- Diagnosis
- Natural History
- Morbidity and Mortality
- Osteoporosis in Men
- Conclusion
- 209 Pathophysiology of Osteoporosis
- Key Points
- Introduction
- Inadequate Peak Bone Mass
- Pathophysiology of Bone Loss
- Gonadal Hormones
- Nongonadal Hormones
- Microbiome
- Chronic Diseases and Medications
- 210 Biochemical Markers of Bone Turnover in Postmenopausal Osteoporosis
- Key Points
- Introduction
- Bone Turnover
- Bone Remodeling
- Bone Turnover Assessment
- Bone Cells
- Practical Aspects
- Choice of Bone Turnover Markers
- Variability
- Diseases and Drugs
- Osteoporosis
- Prediction of Fractures
- Diagnosis of Osteoporosis
- Treatment of Osteoporosis
- Bone turnover marker measurements at the beginning of treatment
- Bone Turnover Markers in Males
- Conclusion
- 211 Management of Osteoporosis
- Key Points
- Introduction
- Recommendations for Treatment
- Evaluation for Secondary Osteoporosis
- Treatment
- Calcium and Vitamin D Supplementation
- Other Lifestyle Modifications
- Prevention of Falls
- Hip Pads and Other Assistive Devices
- Pharmacologic Interventions
- Estrogen Agonist-Antagonists
- Newer Estrogen Agonist-Antagonists
- Calcitonin
- Bisphosphonates
- Alendronate
- Risedronate
- Ibandronate
- Zoledronate
- Denosumab
- Side Effects of Antiresorptive Agents
- Teriparatide (Anabolic Therapy) Versus Antiresorptive Therapy
- Abaloparatide (PTHrP 1–34)
- Romosozumab
- Sequential Therapy
- Management of Vertebral Fractures
- Operative Management
- Summary
- 212 Glucocorticoid-Induced Osteoporosis
- Key Points
- Introduction
- Pathophysiology of Glucocorticoid Bone Loss
- Epidemiology
- Investigations
- Trabecular Bone Score
- Advanced Imaging
- Biochemical Markers
- Management
- Risk Stratification
- Current Recommendations
- Calcium and Vitamin D
- Calcitonin
- Bisphosphonates
- Risedronate
- Parathyroid Hormone
- Receptor Activator of Nuclear Factor κB Ligand Inhibition: Denosumab
- Sclerostin Inhibitor: Romosozumab
- Care Gap in the Screening, Prevention, and Treatment of Glucocorticoid-Induced Osteoporosis
- Conclusion
- 213 Osteomalacia, Rickets, and Renal Osteodystrophy
- Key Points
- Introduction
- Calcium, Phosphorus, and Vitamin D Metabolism
- Effect of Vitamin D on Bone Metabolism
- Causes of Osteomalacia and Rickets
- Consequences of Vitamin D Deficiency on Bone Mineralization, Mineral ion Homeostasis, and Growth
- Calcium Deficiency
- Phosphate Deficiency: Heritable and Acquired Disorders
- Fanconi Syndrome and Renal Tubular Acidosis
- Aluminum, Fluoride, and Heavy Metal Toxicity
- Drugs
- Clinical Evaluation of Osteomalacia and Rickets
- Biochemistry
- Clinical Findings
- Strategies for the Treatment and Prevention of Osteomalacia
- Renal Osteodystrophy
- Altered Calcium, Phosphate, and Vitamin D Metabolism in Chronic Kidney Disease–Mineral and Bone Disorder
- The Skeletal Defects of Renal Osteodystrophy
- Strategies for the Treatment of Chronic Kidney Disease–Mineral and Bone Disorder
- 214 Paget Disease of Bone
- Key Points
- Summary
- History
- Epidemiology
- Pathogenesis
- Environmental Factors
- Histopathology
- Clinical Features
- Skeletal Sites
- Imaging
- Laboratory Findings
- Differential Diagnosis
- Complications and Natural History
- Treatment
- Bisphosphonates
- Other Drugs
- Supportive Therapy
- Surgery
- Follow-Up and Retreatment
- Conclusion
- Section 19 Other Arthropathies and Miscellaneous Disorders
- 215 Entrapment Neuropathies and Compartment Syndromes
- Key Points
- Introduction
- Upper Extremity
- Ulnar Nerve Compression Syndromes
- Ulnar Tunnel Syndrome
- Median Nerve Compression Syndromes (Forearm Entrapment)
- Pronator Teres Syndrome
- Carpal Tunnel Syndrome
- Anatomy
- Etiology
- Clinical Features
- Tests
- Diagnosis
- Treatment
- Radial Nerve Compression Syndrome
- Lower Extremity
- Meralgia Paresthetica
- Anatomy
- Etiology
- Clinical Features
- Diagnosis
- Treatment
- Peroneal Nerve Entrapment
- Etiology and Clinical Features
- Diagnosis
- Treatment
- Tarsal Tunnel Syndrome
- Anatomy
- Etiology
- Clinical Features
- Diagnosis
- Treatment
- Morton Metatarsalgia (Morton Neuroma, Interdigital Neuritis)
- Anatomy
- Etiology
- Clinical Features
- Diagnosis
- Treatment
- Compartment Syndromes
- Acute Compartment Syndrome
- Chronic Compartment Syndrome
- 216 Complex Regional Pain Syndrome
- Key Points
- Introduction
- History of CRPS
- The Establishment of Pain as a “Fifth Vital Sign”
- Triggers
- Pathogenesis
- Inflammation
- Autoimmunity
- Neurological System Abnormalities
- A Psychological Component to CRPS
- Biomarkers
- Criteria for the Diagnosis of CRPS
- The Budapest Criteria
- Incidence of CRPS Based on Evolving Criteria
- Confusion with Other Diagnoses
- CRPS in Children
- Treatment of CRPS
- Nonpharmaceutical, Nonsurgical Approaches to CRPS
- Medications
- Surgical Intervention
- Integrative Medicine (IM) and Complementary and Alternative Medicine (CAMS)
- Peripheral Nerve Stimulation
- Controversial or Potentially Dangerous Therapies
- CRPS in the Courtroom
- Parallels With the Opioid Epidemic
- Conclusions
- 217 Fibromyalgia and Related Syndromes
- Key Points
- Introduction
- Nociplastic pain syndromes
- Epidemiology
- Genetics
- Observational studies
- Pathophysiology and pathogenesis
- Risk factors
- Cognitive factors
- Clinical features
- Differential diagnosis
- The continuum of fibromyalgia to fibromyalgianess
- Treatment
- Natural history
- 218 Diffuse Idiopathic Skeletal Hyperostosis
- Key Points
- History
- Epidemiology
- Criteria and Characteristic Description
- General Findings
- Clinical Features
- Investigations
- Differential Diagnosis
- Etiology and Pathogenesis
- Metabolic Factors
- Management
- Specific Interventions
- 219 Neuropathic Arthropathy
- Key Points
- History
- Etiology
- Syringomyelia
- Tabes dorsalis
- Leprosy
- Congenital Indifference to Pain
- Meningomyelocele (Spinal Dysraphism)
- Drug-Induced Neuropathic Arthropathy
- Other
- Clinical Features
- Imaging
- Other Imaging Techniques
- Laboratory Investigations and Histologic Analysis
- Differential Diagnosis
- Pathogenesis
- Management
- Acute Neuropathic Arthritis
- Chronic Neuropathic Arthropathy
- Conclusion
- 220 Osteonecrosis
- Key Points
- Introduction
- Epidemiology and Risk Factors
- Trauma
- Glucocorticoids
- Alcohol
- Acute Lymphoblastic Leukemia
- Coagulopathies and Hemoglobinopathies
- Decompression Disease
- Genetic Involvement
- Human Immunodeficiency Virus
- Systemic Lupus Erythematosus
- Transplantation
- Medication-Related Osteonecrosis of the Jaw
- Pathophysiology
- Pathogenesis
- Disturbances of Fat Metabolism
- Intravascular Occlusion
- Elevated Intraosseous Pressure
- Intramedullary Hemorrhage
- Osteocytotoxicity
- Other Participatory Processes
- Clinical Features and Diagnosis
- Differential Diagnosis
- Bone Infarct
- Subchondral Insufficiency Fracture
- Osteonecrosis During Pregnancy
- Imaging
- Plain Radiography
- Radionuclide Bone Scans
- Computed Tomography
- Magnetic Resonance Imaging
- Staging Systems
- Management
- Conservative and Nonsurgical Management
- Core Decompression
- Bone Grafting
- Osteotomy
- Joint Arthroplasty
- Conclusion
- 221 Rheumatoid Manifestations of Endocrine and Metabolic Diseases and Their Management
- Key Points
- Acromegaly
- Clinical Features
- Diabetes Mellitus
- Thyroid Disease
- Hyperparathyroidism
- Adrenal Disorders
- Ochronosis
- Lipid Disorders
- Statin Drug-Associated Muscle Syndromes
- Other Drug-Associated Musculoskeletal Manifestations
- 222 Hemophilia-Associated Arthritis
- Key Points
- Hemophilia
- Epidemiology
- Classification
- Etiology
- Von Willebrand Disease
- Current Issues in Treatment of Hemophilia
- Treatment Options: Current and Emerging
- Coagulation Factor Inhibitors
- Hemophilic Arthritis
- Non-joint-Related Disorders
- Diagnosis
- Imaging
- Pathogenesis of Hemophilic Arthritis
- Management
- Primary Prevention
- Management of Arthritis
- Complications of Hemophilic Arthritis
- Management of Joint Bleeding at Specific Sites
- Summary
- 223 Rheumatologic Manifestations of Hemoglobinopathies
- Introduction
- Sickle Cell Disease
- Diagnosis
- Clinical
- Imaging
- Treatment
- Thalassemia
- Clinical
- Imaging
- Treatment
- 224 Hemochromatosis
- Key Points
- Introduction
- The Hemochromatosis Arthropathy
- Chondrocalcinosis
- Spinal Involvement
- Radiologic Appearance
- Pathophysiology
- Osteoporosis
- Diagnosis
- Treatment
- General Management
- 225 Gaucher Disease
- Key Points
- Epidemiology
- Etiology
- Molecular Biology and Genetics
- Pathogenesis
- Clinical Features
- Hematologic Manifestations and Other Extraskeletal Disorders
- Skeletal Involvement
- Investigations
- Imaging
- Differential Diagnosis
- Management
- Enzyme Replacement Therapy
- Substrate Reduction Therapy
- Supportive Care Measuress
- Experimental Therapies
- 226 Digital Clubbing and Hypertrophic Osteoarthropathy
- Key Points
- History
- Epidemiology
- Classification
- Clinical Features
- Physical Findings
- The Primary Form
- Investigations
- Differential Diagnosis
- Clinical Significance
- Pathology
- Etiology and Pathogenesis
- Prostaglandins and Primary Hypertrophic Osteoarthropathy
- Management
- 227 Miscellaneous Arthropathies
- Key Points
- Cancer-Related Musculoskeletal Syndromes
- Associations of Rheumatologic Diseases with Cancer
- Musculoskeletal Manifestations of Cancer
- Neoplastic Conditions that Mimic Rheumatologic Disease
- Musculoskeletal Side Effects of Oncologic Drugs
- Other Systemic Syndromes with Rheumatologic Features
- Castleman Disease
- POEMS Syndrome
- Whipple Disease
- Syndromes With Predominantly Musculoskeletal Involvement
- Palindromic Rheumatism
- Fibroblastic Rheumatism
- SAPHO Syndrome
- Diabetic Muscle Infarction
- Retroperitoneal Fibrosis
- Foreign Body Synovitis
- Silicone Synovitis
- Pigmented Villonodular Synovitis and Tenosynovitis
- Primary Synovial Osteochondromatosis
- Synovial Hemangioma
- Lipoma Arborescens
- Musculoskeletal Syndromes Associated With Chronic Kidney Disease
- Arthritis and Periarthritis
- β 2 - Microglobulin Amyloidosis
- Gadolinium-Induced Fibrosis (Nephrogenic Systemic Fibrosis)
- Use of Antirheumatic Drugs in Patients Receiving Dialysis
- 228 Heritable Disorders of the Skeleton and Connective Tissues
- Key Points
- Introduction to Genetic Disorders of the Skeleton and Associated Soft Tissues
- Disorders of Bone Density
- Skeletal Dysplasias
- Marfan Syndrome (MIM154700) and Related Conditions
- Clinical Features of Marfan Syndrome
- Diagnosis of Marfan Syndrome
- Ehlers–Danlos Syndrome
- Disorders of Bone Density
- Osteopetrosis
- Osteoscleroses
- Skeletal Dysplasias and Related Conditions
- Osteogenesis Imperfecta (Brittle Bone Syndrome)
- Chondrodysplasias
- Type II Collagenopathies
- Other Miscellaneous Conditions
- Abnormalities in the G Protein Signaling System
- Activating Mutations in GNAS1
- Enzyme Defects and the Skeleton
- Hypophosphatasia
- Alkaptonuria (MIM 203500)
- Mucopolysaccharidoses
- 229 Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders
- Key Points
- Joint Hypermobility
- Hypermobility Assessment Scores
- Assessment of Joints Beyond Hypermobility Scores
- Joint Hypermobility and Musculoskeletal Pain
- Hypermobile Ehlers-Danlos Syndrome
- Clinical Features and Diagnostic Criteria
- Red Flags and Other Types of EDS and Heritable Disorders of Connective Tissue
- Hypermobility Spectrum Disorders
- Clinical Features and Diagnostic Framework
- HSD and hEDS in Younger People
- Comorbidities Associated with hEDS and HSD
- Evaluation and Management of hEDS and HSD
- Pain and Fatigue
- Musculoskeletal Concerns
- Skin Complications
- Gastrointestinal Dysfunction
- Cardiovascular Concerns
- Sleep Apnea and Other Sleep Disorders
- ENT and Dental Concerns
- Mast Cell Activation Disorder
- Urogynecology and Obstetric Concerns
- Psychological and Neurobehavioral (Neurodivergence) Aspects of Care
- Summary
- 230 Bone Tumors
- Key Points
- Introduction
- Metastatic Tumors
- Hematologic Malignancies in Bone
- Primary Bone Tumors
- Metastatic Carcinoma to Bone
- Radiographic Appearance
- Histologic Appearance
- Hematologic Malignancies
- Malignant Lymphoma
- Primary Bone Tumors
- Bone-Forming Neoplasms
- Osteoblastoma
- Osteosarcoma
- Cartilage Neoplasms
- Chondromyxoid Fibroma
- Enchondroma
- Osteochondroma
- Periosteal Chondroma
- Chondrosarcoma
- Fibrous-Like Neoplasms
- Fibrous Dysplasia
- Undifferentiated High-Grade Pleomorphic Sarcoma
- Giant Cell Tumor
- Ewing Sarcoma
- Osteofibrous Dysplasia and Adamantinoma
- Vascular Neoplasms
- Chordoma
- Classification and Diagnostic Criteria
- Acute Rheumatic Fever
- Adult-Onset Still Disease
- Antiphospholipid Syndrome
- Calcium Pyrophosphate Deposition Diseases
- Complex Regional Pain Syndrome
- Diffuse Idiopathic Skeletal Hyperostosis
- Fibromyalgia
- Gout
- Hemophagocytic lymphohistiocytosis
- Hypermobility
- IgG4-Related Disease
- Inflammatory Muscle Disease
- Polymyositis and Dermatomyositis
- Inclusion Body Myositis
- Immune-Mediated Necrotizing Myopathies
- Antisynthetase Syndrome
- Overlap Myositis
- Juvenile Idiopathic Arthritis
- Kashin–Beck Disease
- Osteoarthritis
- Psoriatic Arthritis
- Reactive Arthritis
- Relapsing Polychondritis
- Rheumatoid Arthritis
- Sarcoidosis
- Sjögren Syndrome
- Spondyloarthritis
- Peripheral Spondyloarthritis
- Systemic Lupus Erythematosus
- Systemic Sclerosis and Scleroderma
- Vasculitis
- Dermatologic Addendum to the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides
- Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
- Polyarteritis Nodosa
- Behçet Disease
- Cryoglobulinemia
- Henoch–Schönlein Purpura and Immunoglobulin A Vasculitis
- Childhood Henoch–Schönlein Purpura
- Hypersensitivity Vasculitis
- Kawasaki Disease
- Polymyalgia Rheumatica and Giant Cell Arteritis
- Takayasu Arteritis
- Primary Angiitis of the Central Nervous System
- Periodic Fever Syndromes
- Familial Mediterranean Fever
- Index