This document summarizes the case of a 56-year-old Thai woman who presented with hemoptysis and renal failure. She has a history of tuberculosis as a child and rheumatoid arthritis. On examination, she had coarse lung crepitations and signs of renal impairment. Tests showed p-ANCA positivity. She was diagnosed with microscopic polyangiitis and treated with plasma exchange, antibiotics, and steroids. Her condition gradually improved with treatment.

1. Interesting case conference A woman with hemoptysis and renal failure ประจำวันที่ 27 ตุลาคม 2553 นำเสนอโดย : นพ . ปรัชญา ภัสสรานนท์

9. 21/01/51 28/09/53 30/09/53 3/10/53 11/10/53 16/10/53 21/10/53 26/10/53

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13. CBC 99 / 4.5 89 / 4.3 89 / 4.2 86 / 4.0 53 / 4.3 5.8 / 0.5 BUN/Cr 28 PTT 12 PT 26.6 25.9 26.4 26.1 12.3 22.4 RDW 81.9 77.3 75.3 75.8 83 93 61 MCV 103,000 100,000 64,000 30,000 100,000 136,000 225,000 Platelet 4% 6% 5% 10% 16 19% 7% L% 93% 91% 91% 84% 81 70% 85% N% 10800 9760 8230 10310 7300 4100 7830 WBC 26.1 26.9 23.5 29.1 15 31.2 22.6 Hct 2/10/53 1/10/53 30/9/53 28/9/53 21/9/53 27/10/52 22/12/51

17. What to do next? Bronchoscope? CT scan? Dexamethasone? hemodialysis? Plasma exchange? Continue antibiotic? Kidney biopsy? Doppler ultrasound? Consult nephro? V/Q scan? CPR? Factor VIIa ? Echo? Cyclophosphamide? S p u t u m P C R - T B

18. 28 29 30 1 2 3 4 Pip/Taz FOB

20. What to do next? Bronchoscope? CT scan? Dexamethasone? hemodialysis? Plasma exchange? Continue antibiotic? Kidney biopsy? Doppler ultrasound? Consult nephro? V/Q scan? CPR? Factor VIIa ? Echo? Cyclophosphamide? S p u t u m P C R - T B

22. 28 25 11 18 4 Pip/Taz dexa 5q8 meropenem colistin// colistin Methyl P x3 GTC PRES WBC  , schistocyte PT,PTT  , haptoglobin <10 Sputum – A.baum tracheostomy levofloxacin dexa 5q6 vanco ampho dexa 5q12 Sputum – MRSA yeast P.Ex x7

24. Hct WBC Plt

25. 21/01/51 28/09/53 30/09/53 3/10/53 11/10/53 16/10/53 21/10/53 26/10/53 ไข้ Sputum – A.baum, S.maltophilia

26. 21/01/51 28/09/53 30/09/53 3/10/53 11/10/53 16/10/53 21/10/53 26/10/53

27. 21/01/51 28/09/53 30/09/53 3/10/53 11/10/53 16/10/53 21/10/53 26/10/53 ยังมีเสมหะปนเลือด ,Hct 25 Cr 3.9

28. 21/01/51 28/09/53 30/09/53 3/10/53 11/10/53 16/10/53 21/10/53 26/10/53 รู้ตัวดี ไม่มีไข้ Sputum - MRSA

29. Microscopic polyangiitis

34. 1994 Chapel Hill nomenclature Arthritis Rheum . 1994 Feb;37(2):187-92. Microscopic polyangiitis

35. Clincical Dx primary vasculitis WG surrogate marker Upper airway - bloody nasal discharge/crusting > 1 mo. - sinusitis, otitis media, mastoiditis > 3 mo. - retro-orbital mass or inflammation - subglottic stenosis - Saddle nose, destructive sinonasal disease Lower airway - fixed pulm. infiltrates, nodules, cavity > 1 mo. - bronchial stenosis Ann Rheum Dis . 2007 February; 66 (2): 222–227 classificaton algorithm

37. Indirect immunofluorescence assay

38. cANCA

39. Granulocyte antigen of ANCA MPA, SLE, RA, UC, CD, PSC, AIH Clin Exp Rheumatol 2000: 18: 629-635.

40. Problem with pANCA detection Perinuclear staining by ANA granulocyte-specific ANA? Epitope conformation

42. does ANCA has role in pathogenesis ? I have no MPO Anti-MPO Pauciimmune NCGN Systemic vasculitis lipopolysaccharide Now I have MPO Anti-PR3 and pauciimmune glomerulonephritis ! Normal mice reduced leukocyte rolling augmented adhesion and transmigration across the endothelium Nat Rev Rheumatol . 2010 Nov;6(11):653-64.

43. What does ANCA do with body ? Kelly’s textbook of Rheumatology, 8 th ed.

44. Nat Rev Rheumatol . 2010 Nov;6(11):653-64.

45. Nat Rev Rheumatol . 2010 Nov;6(11):653-64.

46. RITUXIVAS N Engl J Med . 2010 Jul 15;363(3):211-20 N Engl J Med . 2010 Jul 15;363(3):221-32. RAVE Steroid Rituximab x 4 weeks IVCY x 2 pulses Steroid IVCY x 3-6 mo. Azathioprine New Dx AAV and renal involvement Non-blind RCT severe new or relapse 148 WG, 24 MPA double - dummy, noninferiority db-RCT Stone JH. Massachusetts General Hospital . USA Jones RB. Addenbrooke's Hospital . UK Pulse + pred 5 mo. Rituximab x 4 weeks placebo CY Pulse + pred 5 mo. oral CY x 3-6 mo. placebo Rituximab Placebo Aza Azathioprine noninferior I M 18% 18% mortality 36% 42% Severe AE 82% 76% remission Cy (11) Ritu (33) 62% 67% MPA 41% * 57% DAH pt. 42% * 67% relapse pt. 53% 64% Remission without pred Cy (98) Ritu (99) 66% 66% Renal 24% 27% DAH 54% 52% Pulmonary Cy (98) Ritu (99)

47. Where ANCA come frome ? Nat Rev Rheumatol . 2010 Nov;6(11):653-64.

50. Autoimmun Rev . 2010 Oct;9(12):812-9

51. Clinical presentation Murray and Nadel’s Textbook of Respiratory Medicine, 5 th ed. 10–50% of patients . Mononeuritis multiplex reported cerebral infarction Neuro 35–60% of patients . Commonly purpura skin 35–55% of patients . Pain, bleeding, ischemia . Rare visceral aneurysms . GI 10–15% of patients . CHF and pericarditis have been described . Cardiac 0–30% of patients . Scleritis, episcleritis, uveitis . eyes Arthralgias and myalgias in at least 50% of patients musculoskeletal 5–30% of patients, with sinus disease most common Upper airway Segmental necrotizing glomerulonephritis and RPGN is almost universal . renal 25–55% of patients . 10–30% with diffuse alveolar hemorrhage . Fibrosis, focal infiltrates, effusions, pulmonary arterial hypertension pulmonary

52. Pathology Neutrophilic capillaritis without granuloma, fibrinoid necrosis and arterial wall disruption, intra alveolar RBC and hemosiderin-laden macrophages Focal segmental necrotizing glomerulonephritis

53. Murray and Nadel’s Textbook of Respiratory Medicine, 5 th ed.

56. Radiology . 2010 May;255(2):322-41

57. Radiographics . 2002 Jul-Aug;22(4):739-64 consolidation with interlobular septal thickening Ground-glass opacity

58. fine reticular pattern superimposed on a background of groundglass attenuation that is the crazy-paving pattern J Comput Assist Tomogr . 2004 Sep-Oct;28(5):710-6

59. F 74y MPO. F/U HRCT show new honeycombing at 5 months 3 mo.

60. M 60Y MPO resemble IPF CT show GGO and reticulation in subpleural region VAT Bx shows irregular interstitial fibrotic thickening, hemosiderin laden macrophages Radiology . 2010 May;255(2):322-41

62. Arthritis Rheum . 1999 Mar;42(3):421-30

66. Induction Maintenance WG MPA oral cyclophophamide+bactrim steroid oral CY

67. Induction Maintenance WG MPA oral cyclophophamide+bactrim steroid pulse IVCY  less SE Azathioprine = oral CY Methotrexate = Aza MTX = oral CY non-organ threatening AAV NORAM 2005 CYCLOPS 2009 Rituximab = IVCY RITUXIVAS 2010 Rituximab > oral CY relapse AAV, DAH RAVE 2010 PE > methylpred severe renal AAV MEPEX 2007 Etanercept add-on WGET 2005 oral CY CYCAZAREM 2003 Pagnoux 2008 Leflunomide > MTX more AE Metzler 2007 MMF > IVCY mild renal MPA IMPROVE (terminated) Weixin 2010 open RCT n=35 MMF < Aza Bactrim add on Nat Rev Rheumatol. 2010 Nov;6 ( 11 ): 653-64 .

69. Thank You