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ANCA Vasculitis

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Slide 1 :

ANCA Vasculitis Erin Hummert February 20, 2008

Slide 2 :

Overview Clinical Manifestations of Wegeners ANCA Associated Diseases Patterns/Antibodies associated with ANCA Vasculitidies Diagnostic Accuracy of ANCA Treatment of Wegeners

Slide 3 :

Classification of Vasculitidies

Slide 4 :

Wegener’s Clinical Manifestations Upper airway/Sinus complaints Pulmonary involvement Renal Involvement Polyarthralgias/Myalgias Ocular symptoms Skin Nervous system Systemic symptoms

Slide 5 :

ANCA Associated Diseases Wegener’s granulomatosis 90% with active disease; 60% with limited disease Microscopic polyangiitis-70% positive Churg-Strauss syndrome-about 50% Renal limited (pauci-immune) vasculitis Drug-induced ANCA-associated vasculitis PTU, Hydralazine, Minocycline

Slide 6 :

Patterns of ANCA Immunofluorescence More sensitive than ELISA. Often screening test Patterns C-ANCA-often related to antibodies to PR3 P-ANCA-Antibody often directed against MPO Atypical pattern can be seen in connective tissue disorder, inflammatory bowel disease and autoimmune hepatitis. Can be confused with P-ANCA

Slide 7 :

Pitfalls of Immunofluorescence Subjective component Unstandardized No reference range for normal ranges Not highly specific for vasculitis C-ANCA >specificity than P-ANCA Specificity can be improved by ELISA for specific antibodies to PR3 and MPO

Slide 8 :

ANCA Antigens

Slide 9 :

How good of a diagnostic tool is ANCA? Large Multicenter European collaborative study Comparing 169 newly diagnosed and 189 previously diagnosed patients with idiopathic systemic vasculitis or RPGN with 184 disease controls and 740 healthy patients Combination of Immunofluorescence and ELISA increased sensitivity and specificity C-ANCA+PR3-73% sens, 99% specific for Wegeners P-ANCA+MPO-67% sens, 99% specific for MPA P-ANCA+MPO-82% sens, 99% specific for Churg-Strauss

Slide 10 :

Bottom Line Classic presenting symptoms plus a positive immunofluorescence and ELISA is likely vasculitis. However, most still recommend every attempt to obtain a histological diagnosis should be attempted Renal biopsy reveals segmental necrotizing glomerulonephritis that is pauci-immune Remember these diseases are not always ANCA positive

Slide 11 :

Treatment of Wegener’s Granulomatosis Initial therapy Daily cyclophosphamide and glucocorticoids Glucocorticoids + Monthly intravenous cyclophosphamide X 6 months Maintenance Methotrexate Azathriopine

Slide 12 :

Plasmapheresis Renal Disease Controlled trials have shown no benefit except for those requiring dialysis at presentation In patients with severe disease (Cr>5.7) did improve the rate of renal recovery Pulmonary Hemorrhage Retrospective study of 20 patients at UNC showed resolution of PAH in all patients Anti-GBM associated disease

Slide 13 :

References Hagen, ED, Daha, MR, Hermans, J, et al for the ED/BCR project for ANCA assay standardization. Diagnostic value of standardized assays for anti-neutrophilic cytoplasmic antibodies in idiopathicsystemic vasculitis. Kidney Int 1998; 53:743 Jayne, DR, Gaskin, G, Rasmussen, N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007; 18:2180. Jenette, JC, Wilkman, AS, Falk, RJ. Diagnostic predictive value of ANCA serology. Kidney Int 1998; 53:796 Klemmer, PJ, Chalermskulrat, Reif, MS, et al. Plasmapheresis therapy for diffuse alveolar hemorrhage in patients with small-vessel vasculitis. Am J Kidney Dis 2003; 42:1149 Nachman, PH, Hogan, SL, Jennette, JC, Falk, RJ. Treatment response and relapse in antineutrophil cytoplasmic antibody-associated microscopic polyangiitis and glomerulo

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Microscopic polyangiitis-70% positive; Churg-Strauss syndrome-about 50%; Renal limited (pauci-immun more Microscopic polyangiitis-70% positive; Churg-Strauss syndrome-about 50%; Renal limited (pauci-immune) vasculitis; Drug-induced ANCA-associated vasculitis ... less

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