ANCA-associated Vasculitis: Diagnostic Therapeutic Strategy

Abstract

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.

Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis: the JMAAV study

“…Patients positive for MPO-ANCA, who had newly diagnosed MPA according to the diagnostic criteria for MPA of the Research Group of Intractable Vasculitis, MHLW of Japan [9], were screened for eligibility. ANCA was tested by enzyme-linked immunosorbent assay (ELISA) for MPO or PR3.…”

De novo myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis 31 years after living-donor kidney transplantation

“…ANCA reacts with myeloperoxidase (MPO) and proteinase 3 (PR3), and can be a specific disease marker [1]. MPO-ANCA-associated disease is common in Japan, whereas PR3-ANCA-associated disease is much more common in western countries [2]. The mean age of onset of MPO-ANCA-associated GN in Japan is reported to be 66.6 years old [3] and the annual incidence of ANCA-associated vasculitis is 22.6 per million adults [4].…”

Wegener’s granulomatosis presenting with life-threatening lung hemorrhage in a 7-year-old child

“…It usually onsets in adolescence and is rare in young children [2,3]. Its diagnosis is usually based on the presence of fever with arthralgia and weight loss, associated with symptoms of upper and/or lower respiratory tract and renal involvement [1][2][3][4]. Massive hemoptysis has been described with the other signs and symptoms and, when particularly acute, can be associated with a very poor prognosis [5][6][7].…”

“…Wegener's granulomatosis (WG) is an idiopathic systemic disease that is characterised by necrotising vasculitis predominantly involving the small vessels, associated with granulomatous inflammation, pauci-immune necrotising crescentic glomerulonephritis and, in most patients, antineutrophil cytoplasmic antibodies (ANCA) [1][2][3][4]. It usually onsets in adolescence and is rare in young children [2,3].…”