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Background: Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity.Objective: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission.Design: Randomized, controlled trial. Random assignments were computer-generated; allocation was concealed by faxing centralized treatment assignment to providers at the time of enrollment. Patients, investigators, and assessors of outcomes were not blinded to assignment.Setting: 42 centers in 12 European countries.Patients: 149 patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease.Intervention: Pulse cyclophosphamide, 15 mg/kg every 2 to 3 weeks (76 patients), or daily oral cyclophosphamide, 2 mg/kg per day (73 patients), plus prednisolone.Measurement: Time to remission (primary outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes).Results: Groups did not differ in time to remission (hazard ratio, 1.098 [95% CI, 0.78 to 1.55]; P = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87.7%). Thirteen patients in the pulse group and 6 in the daily oral group achieved remission by 9 months and subsequently had relapse. Absolute cumulative cyclophosphamide dose in the daily oral group was greater than that in the pulse group (15.9 g [interquartile range, 11 to 22.5 g] vs. 8.2 g [interquartile range, 5.95 to 10.55 g]; P < 0.001). The pulse group had a lower rate of leukopenia (hazard ratio, 0.41 [CI, 0.23 to 0.71]).Limitations: The study was not powered to detect a difference in relapse rates between the 2 groups. Duration of follow-up was limited.Conclusion: The pulse cyclophosphamide regimen induced remission of ANCA-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia.Primary Funding Source: The European Union. [ABSTRACT FROM AUTHOR]

BACKGROUND: Secondary vasculitis represents a rare extraintestinal manifestation of Crohn's disease (CD). Appropriate and prompt diagnosis is often delayed by uncertainties about the relationship of the vasculitic manifestations and CD. OBJECTIVE: To describe our experience with vasculitis in CD and review the literature with respect to different manifestations and pathophysiological aspects of extraintestinal vasculitic manifestations of CD. METHODS: We report 2 new cases of CD with secondary small-vessel vasculitis. We also extensively review the literature (1960-2007) using a broad range of key words related to secondary vasculitis in CD. Relevant publications were evaluated for the number of reported patients and manifestations of vasculitis. RESULTS: Vasculitis is a rare extraintestinal manifestation of CD. Different types of vasculitis affect large-, medium-, and small-sized vessels associated with CD. Common immunologic features include intestinal inflammation as well as an infiltration of gammadelta-T-cells and/or Th1-type cells into vessel walls. The 2 new cases of secondary vasculitis in CD reported here reflect 2 major types of CD-related inflammatory vascular disorders. The first involves the central nervous system, while the second represents circumscribed Musculus gastrocnemius involvement (so-called 'gastrocnemius myalgia syndrome'). Successful treatment of refractory secondary vasculitis in CD with an anti-tumor necrosis factor-alpha antibody is shown for the first time. CONCLUSION: Vasculitis secondary to CD is an uncommon finding. Therefore, it has to be carefully differentiated from other forms of primary or secondary vasculitis with intestinal involvement. Treatment with an anti- tumor necrosis factor-alpha antibody may prove a treatment option in vasculitis as an extraintestinal manifestation of CD. Copyright © 2009 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Standard therapy for antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV) with cyclophosphamide (CYC) and prednisolone is limited by toxicity. This unblinded, prospective, randomized, controlled trial was undertaken to determine whether methotrexate (MTX) could replace CYC in the early treatment of AASV. METHODS: Patients with newly diagnosed AASV, with serum creatinine levels <150 mumoles/liter, and without critical organ manifestations of disease were randomized to receive either standard oral CYC, 2 mg/kg/day or oral MTX, 20-25 mg/week; both groups received the same prednisolone regimen. All drug treatments were gradually tapered and withdrawn by 12 months. Followup continued to 18 months. The primary end point was the remission rate at 6 months (noninferiority testing). RESULTS: One hundred patients were recruited from 26 European centers; 51 patients were randomized to the MTX group and 49 to the CYC group. At 6 months, the remission rate in patients treated with MTX (89.8%) was not inferior to that in patients treated with CYC (93.5%) (P = 0.041). In the MTX group, remission was delayed among patients with more extensive disease (P = 0.04) or pulmonary involvement (P = 0.03). Relapse rates at 18 months were 69.5% in the MTX group and 46.5% in the CYC group; the median time from remission to relapse was 13 months and 15 months, respectively (P = 0.023, log rank test). Two patients from each group died. Adverse events (mean 0.87 episodes/patient) included leukopenia, which was less frequent in the MTX versus the CYC group (P = 0.012), and liver dysfunction, which was more frequent in the MTX group (P = 0.036). CONCLUSION: MTX can replace CYC for initial treatment of early AASV. The MTX regimen used in the present study was less effective for induction of remission in patients with extensive disease and pulmonary involvement and was associated with more relapses than the CYC regimen after termination of treatment. The high relapse rates in both treatment arms support the practice of continuation of immunosuppressive treatment beyond 12 months. [ABSTRACT FROM AUTHOR]

Antineutrophil cytoplasmic antibodies (ANCA) are generally believed to be strongly associated with some primary systemic vasculitides (PSV), such as Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS), which have some clinical manifestations in common and are 'pauci-immune' by immunohistology. This group of PSV has thus been termed 'ANCA-associated vasculitis' (AAV). By contrast, essential mixed cyroglobulinaemic vasculitides (EMC) are clinically heterogeneous and characterized immunologically by complement consumption and by immunocomplex depositions; they are also characteristically ANCA-negative. [ABSTRACT FROM PUBLISHER]

In 2011, the year that subtypes of ANCA-associated vasculitis (AAV) were officially renamed according to key pathological characteristics, important progress was made not only in differentiating these subtypes, but also in understanding—and treating—their eponymous manifestations. [ABSTRACT FROM AUTHOR]