Ozaki Shoichi
Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Allergol Int. 2007 Jun;56(2):87-96. doi: 10.2332/allergolint.R-07-141. Epub 2007 May 1.
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. 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 non-renal 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.
在小血管炎中，显微镜下多血管炎（MPA）、韦格纳肉芽肿病（WG）和变应性肉芽肿性血管炎（AGA）因抗中性粒细胞胞浆抗体（ANCA）参与共同发病机制而统称为ANCA相关性血管炎（AAV）。与血管炎相关的ANCA主要靶抗原是髓过氧化物酶（MPO）和蛋白酶3（PR3）。MPO-ANCA与MPA和AGA相关，PR3-ANCA是WG中的标记抗体。MPO-ANCA相关性血管炎在日本更为常见，而PR3-ANCA相关性血管炎在欧洲和美国更为普遍。ANCA似乎通过直接激活中性粒细胞来诱发血管炎。因此，在血管炎病变中未检测到免疫球蛋白或补体成分；因此，AAV被称为寡免疫性血管炎（pauci = 少/几乎没有）。未经治疗的严重多器官受累AAV患者预后较差，环磷酰胺和大剂量皮质类固醇联合治疗可改善预后。关于AAV诱导缓解和维持缓解的随机对照试验（RCT）表明，标准方案在6个月内的诱导缓解率约为90%，口服硫唑嘌呤和环磷酰胺均可实现缓解维持，甲氨蝶呤仅可用于非肾性轻度AAV。由于这些数据大多是在PR3-ANCA阳性患者中获得的，因此在将这些结果应用于大多数为MPO-ANCA阳性的日本患者时必须谨慎。目前正在进行一项前瞻性研究，以阐明标准方案对日本MPO-ANCA相关性血管炎患者的有效性。本文介绍了AAV的诊断标准和最新的循证治疗策略。
