Small-Vessel Vasculitis

Jennette, J. Charles; Falk, Ronald J.

doi:10.1056/nejm199711203372106

Cited by 1,234 publications

(916 citation statements)

References 73 publications

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“…Of the patients in whom remission was achieved during the treatment period, 32 of 46 in the MTX group (69.5%) had a relapse, as compared to 20 of 43 in the CYC group (46.5%). Time to relapse from remission was longer in the CYC group than in the MTX group (P ϭ 0.023), as shown in Figure 4 (median 13 months [range [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] in the MTX group, and 15 months [range [4][5][6][7][8][9][10][11][12][13][14][15][16][17] in the CYC group) (hazard ratio for MTX versus CYC 1.85 [95% CI 1.06-3.25]). In the MTX group there were 14 major and 18 minor relapses; of the latter, 3 were followed by major relapses.…”

Section: Patientsmentioning

confidence: 83%

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Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody–associated vasculitis

Groot¹,

Rasmussen²,

Bacon³

et al. 2005

Arthritis & Rheumatism

715

400

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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 moles/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 All drug treatments were gradually tapered and withdrawn by 12 months.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.Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are the major categories of primary antineutrophil cytoplasmic antibody (ANCA)-

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Section: Patientsmentioning

confidence: 83%

“…They are characterized by necrotizing small vessel vasculitis and circulating antineutrophil cytoplasmic antibodies (ANCA) (2,3). Improved diagnostic procedures have enabled their earlier diagnosis and have improved awareness of these diseases (4).…”

mentioning

confidence: 99%

Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody–associated vasculitis

Groot¹,

Rasmussen²,

Bacon³

et al. 2005

Arthritis & Rheumatism

715

400

View full text Add to dashboard Cite

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“…A nti-neutrophil cytoplasmic autoantibodies (ANCA) are found in patients with systemic small-vessel vasculitis (1)(2)(3). A pathogenic role of ANCA interacting with ANCA-antigen-containing neutrophils and monocytes was suggested by numerous in vitro studies (4 -10).…”

mentioning

confidence: 99%

Membrane Proteinase 3 Expression in Patients with Wegener’s Granulomatosis and in Human Hematopoietic Stem Cell–Derived Neutrophils

Schreiber

Otto

et al. 2005

Journal of the American Society of Nephrology

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A large membrane proteinase 3 (mPR3)-positive neutrophil subset (mPR3 high ) is a risk for Wegener's granulomatosis (WG).The relationship between mPR3 expression and clinical manifestations was investigated in 81 WG patients and mPR3 expression was studied in CD34 ؉ stem cell-derived human neutrophils. The mPR3 high neutrophil percentage correlated with renal function, anemia, and albumin at the time of presentation. The mPR3 high neutrophil percentage and renal failure severity correlated directly after 5 yr. For elucidating mechanisms that govern mPR3 expression, studies were conducted to determine whether the genetic information that governs mPR3 expression resides within the neutrophils, even without stimuli possibly related to disease. CD34 ؉ hematopoietic stem cells were differentiated to neutrophils, and their mPR3 expression was determined. A two-step amplification/differentiation protocol was used to differentiate human CD34 ؉ hematopoietic stem cells into neutrophils with G-CSF. The cells progressively expressed the neutrophil surface markers CD66b, CD35, and CD11b. The ferricytochrome C assay demonstrated a strong respiratory burst at day 14 in response to PMA but none at day 0. Intracellular PR3 was detectable from day 4 by Western blotting. An increasing percentage of a mPR3-positive neutrophil subset became detectable by flow cytometry, whereas a second subset remained negative, consistent with a bimodal expression. Finally, human PR3-anti-neutrophil cytoplasmic autoantibodies induced a stronger respiratory burst, compared with human control IgG in stem cell-derived neutrophils. Taken together, these studies underscore the clinical importance of the WG mPR3 phenotype. The surface mPR3 on resting cells is probably genetically determined rather than being dictated by external factors.

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“…It is defined as a necrotizing small-vessel vasculitis with few or no immune deposits [6]. In other words, MPA is the pauci-immune SVV in the absence of evidence for GPA (WG) or EGPA (CSS) [25]. Current clinical methods have revealed that at least 80-90 % of MPA (mostly MPO-ANCA) and GPA (WG) (mostly PR3-ANCA) patients and approximately 40 % of EGPA (CSS) patients have ANCA [26].…”

Section: Small-vessel Vasculitismentioning

confidence: 99%

Vasculitis: do we know more to classify better?

Batu

Özen

2014

Pediatr Nephrol

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The systemic vasculitides are a heterogeneous group of disorders characterized by the inflammation of blood vessels. The development and implementation of advanced diagnostic tests and genetic studies have resulted in substantial improvement in our understanding of vasculitis pathogenesis, resulting in the revision of the nomenclature and classification for vasculitis. Multicenter, collaborative studies are currently underway to develop improved diagnostic criteria. In this review, the major nomenclature and classification systems for vasculitides are summarized, with special emphasis on those emerging from the recent 2012 Chapel Hill Consensus Conference (CHCC).

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Small-Vessel Vasculitis

Cited by 1,234 publications

References 73 publications

Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody–associated vasculitis

Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody–associated vasculitis

Membrane Proteinase 3 Expression in Patients with Wegener’s Granulomatosis and in Human Hematopoietic Stem Cell–Derived Neutrophils

Vasculitis: do we know more to classify better?

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