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Rheumatoid Arthritis 11/05. Stephanie Boade Silas, M.D. Division of Rheumatology, UUMC. Objectives. Know the epidemiology and risk factors of rheumatoid arthritis. Have a basic understanding of the pathology and pathogenesis of RA.
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Rheumatoid Arthritis11/05 Stephanie Boade Silas, M.D. Division of Rheumatology, UUMC
Objectives • Know the epidemiology and risk factors of rheumatoid arthritis. • Have a basic understanding of the pathology and pathogenesis of RA. • Know the distinctive musculoskeletal and extraarticular clinical features of RA. • Understand how labs and imaging studies are used to make a diagnosis of RA.
Rheumatoid Arthritis • Chronic, systemic inflammatory disease • 1% of North American Caucasians • Peak incidence 4th to 6th decades • Females 2-3X > Males • Pathogenesis unknown
Pathogenesis • Synovial Hyperplasia • Hypercellularity • Inflammatory cells • Joint effusions • Pannus • Invasive synovium • Erodes cartilage and bone
Normal Synovium • Synovial lining • Loosely organized • 1-3 cell layers • Type A = MΦ • Type B = fibroblast • Subsynovium • Few cells • Scattered vessels, nerves, lymphatics
Rheumatoid Synovium • Synovial lining • Hyperplasia • 10 cell layers thick • Subsynovial • T cells: CD4>CD8 • Dendritic cells • MΦ • B cells/Plasma cells • RF • Vast blood supply
Rheumatoid Ankle -- Pannus • Unique to RA • Synovial fibroblast cells migrate over cartilage surface • Transformed phenotype • RANKL-RANK • Osteoclasts at interface
Pathogenesis of Rheumatoid Arthritis Choy, E. H.S. et al. N Engl J Med 2001;344:907-916
Inflammatory Mediators • Cytokines • Products of activated macrophages and fibroblasts • IL-1, TNF-α, IL-6 • Th-1 cell-driven disease • TNF-α, IL-2, IFNγ, IL-12 • Recruit/activate inflammatory cells • Angiogenesis • Adhesion molecule expression
Inflammatory Mediators • Chemokines • Cell surface proteins • Adhesion molecules, membrane bound TNF, RANKL • Costimulatory molecules • CD80 or CD86 on APC bind CD28 T cell • CTLA-4 on T cell also binds CD80/86 – inhibits costim. • Enzymes • Matrix metalloproteinases (MMPs) • Transcription factors • NF-κB, AP-1 • Complement/Immune complexes
Cytokine Signaling Pathways Involved in Inflammatory Arthritis Choy, E. H.S. et al. N Engl J Med 2001;344:907-916
Genetic Monozygotic twins 15-30% concordance HLA-DR4 Shared epitope HLA-DRB1 *0401, 0404, 0101 Homozygosity Increased risk Increased severity Gender Nulliparity 3 mo. after pregnancy Infections Proteus, Mycoplasma EBV, Parvo, HTLV-1 Cigarette smoking Age RA – Etiology/Risk Factors
RA -- Clinical Features • Morning stiffness = hallmark of inflammatory joint disease • Joint inflammation – Synovitis/Effusions • Warmth, swelling, (erythema) • Structural changes • Cartilage loss, bony erosions, periarticular damage
Joint Distribution • Predominantly peripheral synovial joints • Hand and Feet • Symmetric involvement • Hands predominate • Wrist • MCP’s • PIP’s • Not DIP’s
Ulnar deviation at MCP’s Radial deviation at wrists Swan-neck deformities Boutonniere deformities Tendon nodules Tendon rupture 3rd, 4th, and 5th extensor tendons Carpal tunnel syndrome Ulnar neuropathy RA Hand Deformity
RA - Knees • Symmetric lateral and medial joint space loss • Effusions • Synovial proliferation • Baker’s cyst • Posterior herniation of joint capsule • May rupture • Hx and U/S can distinguish • Crescent-sign on exam
RA - feet • MTP synovitis • Direct palpation • Global lateral/medial squeezing • MTP subluxation • Cock-up deformities of toes • Callous formation on soles • Ankles - synovitis/effusions • Tarsal tunnel syndrome -- medial foot and sole paresthesias
RA - Cervical Spine • Apophyseal joint destruction • C4-5 and C5-6 most common • Atlantoaxial Instability • C1-C2 • Tenosynovitis of transverse ligament of C1 • Erosion of odontoid process of C2 • Cranial settling • Neck/Occiput pain, Paresthesias, Pathologic reflexes
Constitutional sx’s Fever/fatigue/wt loss Osteopenia Muscle weakness Skin Eye Lung Kidney Cardiac Vascular Sjogren’s Neurologic Hematologic Felty’s RA—Extraarticular Features
Extraarticular Features • Rheumatoid nodules (15%) • Central necrosis surrounded by palisading fibroblasts and lymphocytes • Subcutaneous, bursal, tendon sheaths • Extensor surfaces / Pressure points • Forearms • Achilles • Ischial area • MTP’s • Flexor surface of fingers
Extraarticular manifestations • Vasculitis • Leukocytoclastic vasculitis • Palpable purpura • Vasculitic lesions on fingers • Mononeuritis multiplex • Visceral involvement (PAN)
Extraarticular RA -- Ocular • Sicca symptoms • Episcleritis • Scleritis
Extraarticular Manifestations • Pulmonary • Pleural effusions • Interstitial lung disease • Nodules • Cardiac • Pericarditis -- < 10% clinically • Myocarditis • Atherosclerosis – 3X increased risk of CAD
Hematologic • Anemia of chronic disease • Low Fe, Low TIBC, Ferritin > 40 - 100 • Felty’s syndrome • Triad • RA • Splenomegaly • Neutropenia • Frequent infections/Leg ulcers • Iron deficiency anemia (NSAIDs)