Systemic vasculitis

1. Systemic vasculitis Dr.

2. Overview • Introduction • Classification • Pathogenesis • Clinical features • Differential diagnosis • Management • Conclusions

3. Introduction • Systemic vasculitides are • Complex • Often serious group of disorders which, • While uncommon, require careful management in order to ensure optimal outcome • Primary systemic vasculitis has an incidence of • > 100 new cases per million Clinical and Experimental Immunology 2010;160:143–60

4. Introduction End Stage Renal Disease (ESRD)

5. Introduction • Despite a significant reduction in mortality as a result of • Standard immunosuppression, most patients experience • Poor quality of life, characterized by • Relapse, persisting low grade disease activity and increasing burden of drug toxicity Clinical and Experimental Immunology 2010;160:143–60

6. Vasculitis classification– the first step

8. Primary Systemic Vasculitis classification

9. Classification of systemic vasculitis

10. Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis • Small vessel vasculitis • Wegener’s granulomatosis • Churg-Strauss syndrome • Microscopic polyangiitis • Henoch-Schonlein purpura • Essential cryoglobulinemic vasculitis • Cutaneous leukocytoclastic angiitis • Medium-sized vessel vasculitis • Polyarteritis nodosa • Kawasaki disease • Large-vessel vasculitis • Giant cell (temporal) arteritis • Takayasu arteritis

11. Classification of systemic vasculitis • 2 major groups based on clinical and histopathological features of vasculitis 1. Large vessel vasculitis: aorta and major branches • Giant cell arteritis / temporal arteritis • Takayasu arteritis 2. Medium-sized vasculitis: medium arteries • Polyarteritis nodosa (PAN) • Kawasaki disease

12. Classification of systemic vasculitis 2. medium-sized vasculitis: arterioles, capillaries and venules • Wegener’s granulomatosis (WG) • Churg-Strauss syndrome (CSS) • Microscopic polyangiitis (MPA) 3. small vessel vasculitis: venules, capillaries • Henoch Schonlein purpura (HSP) • Cryoglobulinaemic vasculitis

14. Epidemiology Clinical and Experimental Immunology 2010;160:143–60

15. Epidemiology • Begin during the 5th, 6th, 7th decades of life • Male predominance • Caucasians have greater incidence than African Americans • Suspicion that Wegener’s more frequent in colder compared to warmer climates, and that microscopic polyangiitis has opposite trend

16. Pathogenesis of vasculitis J Allergy Clin Immunol 2009;123:1226-36

17. Pathogenesis of vasculitis • Antibody mediated inflammation • Wegener’s granulomatosis (WG) • Churg-Strass syndrome (CSS) • Microscopic polyangiitis (MPA)

18. Pathogenesis of vasculitis • Immune complex-mediated inflammation • Henoch SchÖlein purpura (HSP) • Cryoglobulinaemic vasculitis • Polyarteritis nodosa (PAN) • Cell-mediated inflammation • Giant cell arteritis • Takayasu arteritis • Wegener’s granulomatosis (WG) • Churg-Strass syndrome (CSS)

19. Pathogenesis • All three associated with the presence in serum of autoantibodies against components of the cytoplasm of neutrophils: ANCA • ANCA activates neutrophils, which then adhere to endothelial cells and release mediators of inflammation and cell injury

20. Clinical features J Allergy Clin Immunol 2009;123:1226-36

21. Definition – large vessel vasculitis Clinical and Experimental Immunology 2010;160:143–60

22. Definition – medium vessel vasculitis Clinical and Experimental Immunology 2010;160:143–60

23. Definition – small vessel vasculitis Clinical and Experimental Immunology 2010;160:143–60

24. Small vessel pauci-immune vasculitis • Wegener’s granulomatosis: • Necrotizing granulomatous inflammation, most often affecting respiratory tract • Churg-Strauss syndrome: • Occurs in association with asthma, eosinophilia, and necrotizing granulomatous inflammation • Microscopic polyangiitis: • Pauci-immune systemic vasculitis occurring in the absence of asthma and eosinophilia with no evidence of granulomatous inflammation

26. Clinical Manifestations

27. General symptoms • Fever • Malaise • Anorexia • Weight loss • Myalgias • Arthralgias

28. Renal involvement *less frequent in Churg-Strauss *hematuria, proteinuria and renal failure *renal failure usually has characteristics of rapidly progressive glomerulonephritis

29. Skin *Purpura most common in lower extremities, occurs as recurrent crops. *Nodular lesions occur more frequently in Churg-Strauss and Wegener’s

30. Upper and lower respiratory tract *pulmonary hemorrhage *nodular or cavitary lesions in Wegener’s and Churg-Strauss *subglottic stenosis, sinusitis, rhinitis, otitis media, ocular inflammation most common in Wegener’s

31. Cardiac *identified in 50% of pts with Churg-Strauss *<20% in Wegener’s and microscopic polyangiitis *transient heart block, ventricular hypokinesis, infarction, myocarditis, endocarditis, pericarditis

32. Gastrointestinal *typically abdominal pain, blood in the stool, mesenteric ischemia and rarely perforation *can also mimic pancreatitis and hepatitis

33. Diagnosis

34. Update on vasculitis: J Allergy Clin Immunol 2009

35. Update on vasculitis: J Allergy Clin Immunol 2009

38. Differential Dx of Vasculitis • Fibromuscular dysplasia • Cholesterol emboli • Atrial myxoma with emboli • Infective endocarditis • Malignancies,ie lymphamatoid granulomatosis • Bacteremia • Rickettsial dz • Amyloid • SLE

39. Differential Diagnosis: Pulmonary-Renal Syndrome • Goodpasture’s disease • SLE • Henoch-Schoenlein purpura • Behcet’s syndrome • Essential mixed cryoglobulinemia • Rheumatoid vasculitis • Drugs: penicillamine, hydralazine, propylthiouracil • Acute renal failure with hypervolemia • Severe cardiac failure • Severe bacterial pna with renal failure • Hantavirus infection • Opportunistic infections • ARDS w/ renal failure in multi-organ failure • Paraquat poisoning • Renal vein/IVC thrombosis w/ PE

40. Differential of Pulmonary Renal Syndrome Goodpasture’s Disease Systemic Vasculitis Wegener’s Granulomatosis Microscopic Polyangiitis Churg-Strauss Syndrome Cryoglobulinemia Henoch-Schonlein Purpura Connective Tissue Disease Polymyositis/Dermatomyositis Progressive Systemic Sclerosis SLE Primary Glomerular Disease IgA Nephropathy Post-Infectious GN Membranoproliferative GN

41. Anti-neutrophil cytoplasmic autoantibodies • Serologic testing for ANCA is useful diagnostic test, but should be interpreted in the context of other patient characteristics • Testing should include both indirect immunoflourescence microscopy (IFA) and enzyme immunoassay (EIA) • Sensitivity for pauci-immune small vessel vasculitis and GN is 80-90% • ¼- 1/3 of patients with anti-GBM crescentic GN and ¼ of patients with idiopathic immune-complex crescentic GN are ANCA positive • Pts with concurrent ANCA and anti-GBM antibodies have worse prognosis than those with ANCA alone

42. Anti-neutrophil cytoplasmic autoantibodies

44. Pathologic diagnosis • Biopsy of involved site • Skin • Muscle • Nerve • Gut • Kidney

45. Size of vessel involvement • Glomerular vasculitis • Focal necrosis, crescents • Rapidly progressive glomerulonephritis • Extra-glomerular vasculitis • Arteritis of small/medium/large renal arteries

46. Takayasu’ s arteritis Polyarteritis nodosa

48. Crescentic glomerulonephritisClassification by immune deposits

49. Rapidly Progressive glomerulonephritis (RPGN) • Definition and disease associations • The kidney in ANCA vasculitis • Pathogenesis • Treatment and outcomes