ANCA-associated vasculitis: diagnostic and 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. 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.
Ozaki
Shoichi
S
Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan. ozk@marianna-u.ac.jp
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D001379:Azathioprine / Q000627:therapeutic use; D001688:Biological Products / Q000627:therapeutic use; D015267:Churg-Strauss Syndrome / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D014890:Granulomatosis with Polyangiitis / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D053146:Myeloblastin / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014657:Vasculitis / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology / Q000628:therapy*
D000305:Adrenal Cortex Hormones; D019268:Antibodies, Antineutrophil Cytoplasmic; D001688:Biological Products; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009195:Peroxidase; D053146:Myeloblastin; D001379:Azathioprine; D008727:Methotrexate