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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 Arthritis 11/05


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    1. Rheumatoid Arthritis11/05 Stephanie Boade Silas, M.D. Division of Rheumatology, UUMC

    2. 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.

    3. Rheumatoid Arthritis • Chronic, systemic inflammatory disease • 1% of North American Caucasians • Peak incidence 4th to 6th decades • Females 2-3X > Males • Pathogenesis unknown

    4. Pathogenesis • Synovial Hyperplasia • Hypercellularity • Inflammatory cells • Joint effusions • Pannus • Invasive synovium • Erodes cartilage and bone

    5. Normal Joint Diagram

    6. Normal PIP joint

    7. Normal Synovium • Synovial lining • Loosely organized • 1-3 cell layers • Type A = MΦ • Type B = fibroblast • Subsynovium • Few cells • Scattered vessels, nerves, lymphatics

    8. 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

    9. Rheumatoid Ankle -- Pannus • Unique to RA • Synovial fibroblast cells migrate over cartilage surface • Transformed phenotype • RANKL-RANK • Osteoclasts at interface

    10. RA: Erosions

    11. Pathogenesis of Rheumatoid Arthritis Choy, E. H.S. et al. N Engl J Med 2001;344:907-916

    12. 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

    13. 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

    14. Cytokine Signaling Pathways Involved in Inflammatory Arthritis Choy, E. H.S. et al. N Engl J Med 2001;344:907-916

    15. 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

    16. 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

    17. Joint Distribution • Predominantly peripheral synovial joints • Hand and Feet • Symmetric involvement • Hands predominate • Wrist • MCP’s • PIP’s • Not DIP’s

    18. RA: Joint distribution

    19. Synovitis

    20. RA - hands

    21. 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

    22. Swan neck and Boutonniere

    23. Ulnar Deviation

    24. RA- extensor tendon rupture

    25. Carpal Tunnel Syndrome

    26. 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

    27. Popliteal Cyst

    28. Ruptured Baker’s Cyst

    29. 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

    30. MTP subluxation

    31. Cock-up deformity

    32. 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

    33. Atlantoaxial Instability

    34. 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

    35. 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

    36. Rheumatoid nodules

    37. RA - Chronic changes

    38. Extraarticular manifestations • Vasculitis • Leukocytoclastic vasculitis • Palpable purpura • Vasculitic lesions on fingers • Mononeuritis multiplex • Visceral involvement (PAN)

    39. RA - Vasculitis

    40. RA - Vasculitis

    41. Extraarticular RA -- Ocular • Sicca symptoms • Episcleritis • Scleritis

    42. Scleromalacia perforans

    43. Extraarticular Manifestations • Pulmonary • Pleural effusions • Interstitial lung disease • Nodules • Cardiac • Pericarditis -- < 10% clinically • Myocarditis • Atherosclerosis – 3X increased risk of CAD

    44. RA: Pulmonary nodules

    45. RA: Pulmonary fibrosis

    46. 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)