ANCA-associated Vasculitis: Diagnostic Therapeutic Strategy
Among small-vessel vasculitides, microscopic polyangiitis (MPA), Wegener's granulomatosis (WG), and allergic granulomatous angiitis (AGA) are known collectively as ANCA-associated vasculitis (AAV) because of the involvement of anti-neutrophil cytoplasmic antibodies (ANCA) as the common pathogenesis. Major target antigens of ANCA associated with vasculitis are myeloperoxidase (MPO) and proteinase 3 (PR3). MPO-ANCA is related to MPA and AGA, and PR3-ANCA is the marker antibody in WG.
... in WG. MPO-ANCA-associated vasculitis is more frequent in Japan, whereas PR3-ANCA-associated vasculitis is more common in Europe and USA. ANCA appears to induce vasculitis by directly activating neutrophils. Therefore, no immunoglobulins or complement components are detected in the vasculitis lesions; hence, AAV is called pauci-immune vasculitis (pauci = few! little). Untreated patients with severe AAV with multi-organ involvement have a poor prognosis, which is improved by combination therapy with cyclophosphamide and high-dose corticosteroid. Randomized controlled trials (RCT) regarding induction and maintenance of remission of AAV indicated that the rate of remission induction by the standard regimen is approximately 90% in 6 months, that maintenance of remission can be achieved with oral azathioprine as well as cyclophosphamide, and that methotrexate can be used only for nonrenal mild AAV. As these data were obtained mostly in patients positive for PR3-ANCA, caution must be taken in applying these findings to Japanese patients, most of whom are positive for MPO-ANCA. A prospective study is now underway to clarify the effectiveness of the standard regimen in Japanese patients with MPO-ANCA-associated vasculitis. This article describes the diagnostic criteria and the recent evidence-based therapeutic strategy of AAV.