In patients with generalized vasculitis, the withdrawal of cyclophosphamide and the substitution of azathioprine after remission did not increase the rate of relapse. Thus, the duration of exposure to cyclophosphamide may be safely reduced.

No abstract

Anti-neutrophil cytoplasmic antibodies (ANCA) are widely used as diagnostic markers for Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and idiopathic rapidly progressive glomerulonephritis (iRPGN). The objective of this study was to evaluate the diagnostic value of ANCA measurement by the indirect immunofluorescence (IIF) test, and by anti-PR3 and anti-MPO ELISA performed in different locations, in patients with idiopathic small vessel vasculitis. Fourteen centers participated in a standardization study of ANCA assays, and entered a total number of 169 newly diagnosed and 189 historical patients with idiopathic systemic vasculitis or iRPGN. Patients were classified according to a pre-defined diagnostic classification system. Results were compared with those of 184 disease controls and 740 healthy controls. The IIF test was performed according to standard methodology; ELISAs had been standardized among the participants in a previous phase of the study. The sensitivities of assays in patients were as follows. The sensitivity in WG was: cANCA 64%, pANCA 21%, anti-PR3 66%, anti-MPO 24%. In MPA the sensitivity was: cANCA 23%, pANCA 58%, anti-PR3 26%, anti-MPO 58%. Sensitivity in iRPGN was: cANCA 36%, pANCA 45%, anti-PR3 50%, anti-MPO 64%. The specificity of assays (related to disease controls) was: cANCA 95%, pANCA 81%, anti-PR3 87%, anti-MPO 91%. When the results of the IIF test were combined with those of the ELISAs (cANCA/anti-PR3 positive, pANCA/anti-MPO positive), the diagnostic specificity increased to 99%. The sensitivity of the combination of cANCA + anti-PR3 or pANCA + anti-MPO for WG, MPA or iRPGN was 73%, 67% and 82%, respectively. From this study we conclude that the value of the IIF test for ANCA detection can be greatly increased by the addition of a well standardized antigen-specific ELISA. In a significant number of patients with idiopathic small vessel vasculitis, however, the ANCA test results (either in IIF or ELISA) are negative.

tion than glomerulonephritis in relation to WG. This difference Renal histology in ANCA-associated vasculitis: Differences may be due to a delayed establishment of diagnosis in patients between diagnostic and serologic subgroups.with MPA compared to patients with WG. Both active and Background. Differences in renal histopathology between chronic lesions are more abundantly present in MPO-ANCAmicroscopic polyangiitis (MPA) and Wegener's granulomatopositive patients than in patients with PR3-ANCA-positivity, sis (WG), and between anti-neutrophil cytoplasm autoantibody which suggests that the pathogenesis of renal disease in these (ANCA) test results in patients with ANCA-associated vasculi-ANCA subsets could be different. Our results also suggest tis may provide insight into the differences in pathogenesis that ANCA test results may be useful in classifying ANCAand raise the opportunity of classifying the vasculitides more associated vasculitides. accurately. The possible differences in histopathology are investigated in this study.Methods. We report an analysis of 173 patients with renal disease in microscopic polyangiitis or Wegener's granulomato-Rapidly progressive deterioration of renal function sis. A total of 173 renal biopsies, performed at diagnosis, were is a frequent but clinically unfavorable feature of antiscored by two observers separately, using a previously stanneutrophil cytoplasm autoantibody (ANCA)-associated dardized protocol. Consensus on each biopsy was achieved during a central review.vasculitis, including microscopic polyangiitis, Wegener's Results. Normal glomeruli were more common in WG than granulomatosis, and renal limited vasculitis [1]. Usually, in MPA (P Ͻ 0.001). Glomerulosclerosis was more prominent this rapidly progressive deterioration of renal function in MPA than in WG (P ϭ 0.003). Interstitial fibrosis (P Ͻ is histopathologically accompanied by a pauci-immune 0.001), tubular atrophy (P Ͻ 0.001), and tubular casts (P ϭ crescentic necrotizing glomerulonephritis. However, the 0.005) were more frequently present and more severe in MPA than in WG. Presence of glomerulosclerosis was more extensive histopathological features vary among patients from mild in patients with myeloperoxidase (MPO)-ANCA than with focal segmental extracapillary proliferation to diffuse proteinase 3 (PR3)-ANCA (P ϭ 0.022). Interstitial fibrosis crescentic necrotizing glomerulonephritis with granulo-(P ϭ 0.008), tubular necrosis (P ϭ 0.030), tubular atrophy (P ϭ mas and tubular intra-epithelial infiltrates. In some cases, 0.013), and intra-epithelial infiltrates (P ϭ 0.006) were more extensive glomerulosclerosis is found [2]. frequently present and more severe in MPO-ANCA than in PR3-ANCA. The differences between microscopic polyangiitis and Conclusions. Glomerulonephritis in relation to MPA hasWegener's granulomatosis have been described as folmore characteristics of chronic injury at the time of presentalows [3,4]. Microscopic polyangiitis is characterized by a non-granulomatous systemic vasculitis that is as...

This analysis suggests that AAV encompasses five classes associated with different outcomes. As compared with the traditional GPA-MPA separation, this classification system may better reflect the phenotypic spectrum of AAV.