Rheumatology: Back to Basics: 2010

1. Rheumatology: Back to Basics: 2010

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

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

8. Antinuclear Antibody (ANA) Test Results in a Hypothetical Population. Although the ANA may be present before the development of SLE, current estimates of disease incidence and test sensitivity and specificity suggest that most positive results are of uncertain (or no) clinical significance.Antinuclear Antibody (ANA) Test Results in a Hypothetical Population. Although the ANA may be present before the development of SLE, current estimates of disease incidence and test sensitivity and specificity suggest that most positive results are of uncertain (or no) clinical significance.

9. Anti-centromere Antibodies:Limited Systemic Sclerosis (CREST)

10. 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

11. Anti-DNA (double stranded) Sensitivity for SLE: ~60% Specificity: ~ 100% Levels: may correlate with; - disease activity - hypocomplementemia - renal disease

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

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. Wegener�s: cANCA (PR-3) Medium + small vessels Granulomatous Upper +/- lower respiratory Renal

18. Specific Diseases�

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

20. 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

21. OA: Heberden�s (DIP) Bouchard�s (PIP) Nodes

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

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

24. DIPs ? (spared) PIPs ? MCPs ?

25. Rheumatoid Arthritis Deformities Nodules Periarticular osteopenia Marginal erosions

26. 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...

28. RA: Nodules

29. RA: Factors Associated with Poor Prognosis Rheumatoid factor positivity HLA-DR4 haplotype Degree of disease activity at onset � ??? Early aggressive therapy

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

31. RA: Common DMARD�s Methotrexate Hydroxychloroquine Sulfasalazine New Biologics...

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

33. 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

34. Lupus: Criteria 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

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

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

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

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

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

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

41. Raynaud�s phenomenon Cold, stress 3 phases: white ?blue ? red 8-10% of normals 90% - scleroderma Consider ANA when screening (SLE, CREST)

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

43. Limited Scleroderma (CREST)

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

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

46. Question 1: What did Ramses II have, besides riches and fame?

47. Answer: Ankylosing Spondylitis

48. Spondyloarthropathies 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

49. Enthesitis Reiter�s - erosion at Achilles insertion into calcaneus and extra bone at site of plantar fasciitisReiter�s - erosion at Achilles insertion into calcaneus and extra bone at site of plantar fasciitis

50. Achilles tendinitisAchilles tendinitis

51. Inflammatory low back pain? Insidious onset Worse with rest Better with activity Morning stiffness Family history

53. 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%

54. 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)

55. Bacteria that Trigger Reactive Arthritis Post-venereal: Chlamydia trachomatis Post-dysenteric: Salmonella Shigella flexneri Yersinia enterocolitica Campylobacter Clostridium difficile

56. HLA-B27: Reactive Arthritis

57. Spondyloarthropathies: Extra-articular features Skin: Psoriasis, E. nodosum, pyoderma gangrenosum... Eyes: iritis, conjunctivitis Lungs: apical pulmonary fibrosis Cardiac: aortic insufficiency, conduction abnormalities Neurologic: cauda equina...

59. Reiter�s Syndrome

60. Gout Acute monoarthritis - lasts days - recurrent attacks Uncontrolled hyperuricemia ? tophi ? polyarthritis

61. Gout: uric acid crystals Needle-shaped Strong negative bireringence Phagocytosed by PMN�s

62. Gout: Treatment Asymptomatic hyperuricemia ? none Acute attack - NSAID�s - colchicine - steroid�s Indications to lower uric acid - allopurinol - renal stones - frequent attacks - tophi

63. Pseudogout - CPPD Acute monoarthritis Knees, wrists Chondrocalcinosis Pyrophosphate crystals: - rhomboid - weak positive birefringence

64. Vasculitis: Classification Small Vessel Hypersensitivity Medium Vessel: - necrotizing = Polyarteritis nodosa - Kawasaki�s Large Vessel: - Giant Cell (Temporal) arteritis - Takayasu�s (Aortic Arch Syndrome)

65. Vasculitis: ClassificationNB! can have overlap... 1. Large Vessel Vasculitis 2. Medium Vessel Vasculitis 3. Small Vessel Vasculitis

66. Large Vessel Vasculitis - Giant Cell Arteritis - Takayasu�s (Aortic Arch Syndrome)

67. Medium Vessel Vasculitis - Polyarteritis nodosa (PAN) - Kawasaki Disease - Primary CNS Vasculitis

68. Small Vessel Vasculitis - ANCA Associated: - Wegener Granulomatosis - Churg-Strauss Syndrome - Microscopic Polyangiitis (MPA) - Henoch-Sch�nlein Purpura (HSP) - Vasculitis with connective tissue diseases - Vasculitis/essential mixed cryoglobulinemia (Hep C) - Hypersensitivity vasculitis (leukocytoclastic) - Vasculitis with viral infections (Hep B, C, HIV, CMV, parvo-B19)

69. Palpable purpura Most common vasculitis Leukocytoclastic vasculitis Ag (eg. Infection, drug) + Ab ? immune complex Rule out other organ involvement (kidney, lung�)

70. Wegener�s Granulomatosis Small + medium vessels Granulomatous Upper +/- lower respiratory (ulcers, sinuses...) Renal

71. Anti-Neutrophil Cytoplasmic Antibodies (ANCA) Patients with suspected vasculitis: Pulmonary - renal: - Wegener - ...

72. ANCA Immunofluorescence cytoplasmic - cANCA perinuclear � pANCA Solid Phase Assays (ELISA�) : pANCA = anti-MPO (myeloperoxidase) cANCA = anti-PR3 (proteinase 3)

73. cANCA (anti-PR3) Highly sensitive, specific for Wegener�s granulomatosis Specificity: 95%

74. Giant Cell Arteritis (GCA) Age >50 years - mean = 70 years Symptoms related to arteries: - headache, scalp tenderness - visual loss - jaw claudication

75. Giant Cell (Temporal) Arteritis

76. Giant Cell (Temporal) Arteritis Diagnosis: - CBC - anemia of chronic disease - ESR - markedly elevated, often >100 - Biopsy temporal artery Treatment: URGENT! (prevent visual loss) - steroids - prednisone 60mg daily...

78. Fibromyalgia Prevalence 3% widespread pain, tender points sleep disturbance Absence of inflammatory markers� Exclusion of other systemic disorders Treatment: - education - exercise - low dose tricyclic - New = pregabalin, duloxetine

79. NSAIDs, Coxibs

80. Toxicity: ASA and NSAIDs GI: ulcers, bleeding CVS: hypertension, increased risk MI, stroke Renal: Na retention, edema, renal failure CNS platelet effects contraindicated ASA hypersensitivity avoid if possible - pregnancy and lactation

81. Cox-2 �specific� Inhibitors (coxibs) improved GI safety no effect on platelets efficacious in RA, OA, pain ?? Increased risk MI, stroke renal effects like other NSAID�s ? caution! - elderly - hypertension - cardiac disease - renal disease