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Rheumatology: Back to Basics: 2012

Rheumatology: Back to Basics: 2012. James Gillray “The Gout” 1799. Immune Mechanisms of Disease. Type I: Anaphylactic IgE eg. asthma Type II: Cytotoxic eg. AIHA Type III: Immune Complex eg. SLE Type IV: Cell-mediated/Delayed Hypersensitivity: T-cells eg. Contact dermatitis.

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Rheumatology: Back to Basics: 2012

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  1. Rheumatology: Back to Basics: 2012 James Gillray “The Gout” 1799

  2. Immune Mechanisms of Disease • Type I: Anaphylactic IgE eg. asthma • Type II: Cytotoxic eg. AIHA • Type III: Immune Complex eg. SLE • Type IV: Cell-mediated/Delayed Hypersensitivity: T-cells eg. Contact dermatitis

  3. GENETICS ENVIRONMENT Infections... AUTOIMMUNITY

  4. HLA: Disease Associations • HLA B27 (MHC Class I) - Ankylosing Spondylitis - Reiter’s/reactive arthritis - Psoriatic arthritis - IBD arthropathy • HLA DR4, DR1 (MHC Class II) - RA • HLA DR3 (MHC Class II) - SLE, Sjogren’s, Type I DM…

  5. We love our antibodies...

  6. Rheumatoid Factor • Anti-antibodies (Fc domain of IgG) • Rheumatoid Arthritis: - sensitivity = 70% - poor prognosis - extra-articular features • Non-specific: - other rheumatic diseases eg. Sjogren’s - chronic inflammatory diseases - chronic infections – SBE, Hep C - 10-20% over age 65

  7. Anti-Citrullinated Peptide Antibodies (CCP or ACPA) • More specific for RA • More sensitive than RF in early RA • Associated with worse prognosis

  8. Antinuclear Antibodies • Sensitivity for SLE 90%+ • Specificity low - other autoimmune diseases - family members - drugs - ...

  9. Cold, stress 3 phases: white blue red 5 of normals 90% - scleroderma Consider ANA when screening(SLE, CREST) Raynaud’s phenomenon

  10. ANA: Anti-centromere pattern:Limited Systemic Sclerosis (CREST)

  11. Other Autoantibodies • Anti-DNA(native, double-stranded) - SLE- sensitivity 60-70% - specificity ~ 100% - correlate with disease activity • Anti-SSA, SSB (Ro, La) - Sjogren’s, SLE - congenital complete heart block

  12. Antibodies to Ro/SSA • 30-35% of patients with Lupus • Associated with: - Sjogren’s syndrome - photosensitive rashes “subacute cutaneous lupus” - Neonatal lupus - transient rashes - congenital complete heart block

  13. Antibodies to Ro/SSA Adult: Subacute Newborn: Cutaneous Lupus Neonatal Lupus

  14. Antiphospholipid Antibodies • Anticardiolipin antibodies • Lupus anticoagulant • Associations: - thrombosis - recurrent pregnancy losses • SLE, other CTD’s, primary

  15. Patients with suspected vasculitis: - Wegener’s - pulmonary/renal - RPGN - cocaine Anti-Neutrophil Cytoplasmic Antibodies (ANCA) Cytoplasmic Perinuclear

  16. Anti-Neutrophil Cytoplasmic Antibodies (ANCA) • Patients with suspected vasculitis - pulmonary/renal syndromes • cANCA: Wegener’s Granulomatosus: - 80% sensitive and specific - specificity is for PR-3 • pANCA: less specific

  17. Specific Diseases…

  18. Osteoarthritis (OA) • The most common type of arthritis • Disease of cartilage (cf. RA) • Characterized by: - Cartilage degradation, loss - hypertrophic bone formation (osteophytes...

  19. Primary (idiopathic) OA • Peripheral Joints: - hands - DIP, PIP (cf. RA) - 1st C-MC - feet - 1st MTP - large weight-bearing joints - hips, knees • Spine - apophyseal joints - intervertebral discs

  20. OA: Heberden’s (DIP) Bouchard’s (PIP) Nodes

  21. Joint space narrowing Subchondral sclerosis Osteophytes Osteoarthritis: X-ray 1st C-MC Joint

  22. Prevalence 1:100 small joint, symmetric polyarthritis + AM stiffness chronic (>6weeks) Path = synovial inflammation Extra-articular features Rheumatoid Arthritis

  23. DIPs  (spared) • PIPs  • MCPs 

  24. Deformities Nodules Periarticular osteopenia Marginal erosions Rheumatoid Arthritis

  25. RA: Extra-articular Features • Skin - sc nodules, vasculitis... • Eyes - sicca, scleritis, episcleritis • Lungs - pleurisy/effusion - interstitial fibrosis - nodules • Cardiac - pericarditis, nodules • Hematologic - anemia, - Felty’s (neutropenia…) • Neurologic - peripheral neuropathy...

  26. Scleritis

  27. RA: Nodules

  28. RA: Factors Associated with Poor Prognosis • RF, anti-CCP (ACPA) positivity • HLA-DR4 haplotype • Degree of disease activity at onset • …  Early aggressive therapy

  29. RA: Treatment • Symptomatic - rest, education - splints, orthotics - ASA, NSAID’s, Coxibs • Disease Modifying Anti-Rheumatic Drugs (DMARDs)

  30. RA: Common DMARD’s • Methotrexate • Hydroxychloroquine • Sulfasalazine • New Biologics...

  31. RA: New Therapies - Biologics • anti-TNF • soluble TNF receptor • Concerns: - cost - parenteral - risk of infections, TB

  32. Systemic Lupus Erythematosus • Affects 1:1-2000 individuals • African American blacks > Asian > Caucasian • Females : Males = 9:1 • Any age - usually young females in their reproductive years

  33. Malar rash Photosensitivity Discoid rash Mucosal ulcers Arthritis Serositis “Pleurisy” Renal CNS Hematology: anti-WBC anti-platelet anti-rbc Immunologic: anti-DNA anti-phospholipid anti-Sm Antinuclear antibodies Lupus: Criteria

  34. SLE: Organs Affected • Joints: 80-90% • Skin: 70%, often photosensitive • Serositis: 50% • Kidneys: 25-50% • CNS: 15%

  35. Plaques Photosensitive Often head & neck Scarring 10% develop SLE Discoid Lupus

  36. Lupus: Treatment • Sunscreens, sunprotection • Anti-inflammatory drugs • Anti-malarial drugs • Steroids • Immunosuppressants • Mycophenolate mofetil

  37. Systemic Sclerosis (Scleroderma):Skin thickening, tightening

  38. Scleroderma • Disorder of: - small blood vessels = SPASM, ischemia + - overproduction of connective tissue (collagen) = FIBROSIS

  39. Systemic - Diffuse - Limited (CREST) - anti-centromere Localized - morphea - linear scleroderma Scleroderma: Types

  40. Scleroderma • Lungs - fibrosis - Pulmonary hypertension • GI - GERD... • Renal - malignant hypertension - microangiopathic anemia - renal failure - ACEI !!!!!!!!!!!!!!!!!!!

  41. Limited Scleroderma (CREST) Calcinosis Telangiectasias

  42. Infection Crystal (gout, pseudogout) Spondyloarthropathy Acute Monoarthritis (in absence of trauma)

  43. Synovial Fluid Testing • Cell count, differential WBC: 200-2000 = non-inflammatory 2000-100,000 = inflammatory >75,000 = septic • Gram stain, C&S • Crystals

  44. Ankylosing Spondylitis Reiter’s/reactive arthritis Psoriatic arthritis Inflammatory Bowel Disease Axial and/or peripheral joints HLA-B27 Path = enthesopathy Inflammatory back pain Extra-articular: - uveitis etc. RF negative Spondyloarthropathies

  45. Enthesitis Erosion Calcaneal Spur

  46. Inflammatory low back pain? • Insidious onset • Worse with rest • Better with activity • Morning stiffness • Family history Bilateral Sacroiliitis

  47. Ankylosing Spondylitis

  48. HLA-B27: Disease Associations • Ankylosing Spondylitis >90% • Reiter’s syndrome/ reactive 80% • Inflammatory bowel disease 50% • Psoriatic Arthritis - with spondylitis 50% - with peripheral arthritis 15% • Caucasians 8% • Inuit 25%

  49. Reactive Arthritis: Concept • A sterile inflammatory arthritis - triggered by an infection - at a distant site (GI or GU) - in a genetically susceptible host • An inflammatory reaction to a persistent organism or antigen(s)

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