Relapse Of ANCA-associated Vasculitis Research Articles

Autoantibodies towards HFE and SYT5 in anti-neutrophil cytoplasm antibody-associated vasculitis relapse.

Identification of those at high and low risk of disease relapse is a major unmet need in the management of patients with ANCA-associated vasculitis (AAV). Precise stratification would allow tailoring of immunosuppressive medication. We profiled the autoantibody repertoire of AAV patients in remission to identify novel autoantibodies associated with relapse risk. Plasma samples collected from 246 AAV patients in remission were screened for novel autoantibodies using in-house generated protein arrays including 42 000 protein fragments representing 18 000 unique human proteins. Patients were categorized based on the occurrence and frequency of relapses. We modelled the association between these antibodies and relapse occurrence using descriptive and high dimensional regression approaches. We observed nine autoantibodies at higher frequency in samples from AAV patients experiencing multiple relapses compared with patients in long-term remission off therapy (LTROT). LASSO analysis identified six autoantibodies that exhibited an association with relapse occurrence after sample collection. Antibodies targeting HFE and SYT5 were identified as associated with relapse in both analyses. Through a broad protein array-based autoantibody screening, we identified two novel autoantibodies directed against HFE and SYT5 as candidate biomarkers of relapse in AAV.

Computable phenotype for real-world, data-driven retrospective identification of relapse in ANCA-associated vasculitis

ObjectiveANCA-associated vasculitis (AAV) is a relapsing-remitting disease, resulting in incremental tissue injury. The gold-standard relapse definition (Birmingham Vasculitis Activity Score, BVAS>0) is often missing or inaccurate in registry settings, leading...

Disease Activity and Tendency to Relapse in ANCA-Associated Vasculitis Are Reflected in Neutrophil and Intermediate Monocyte Frequencies.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases with inflammation affecting small blood vessels and includes granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). In this study, we investigated granulocyte and monocyte subsets in a large cohort of AAV patients with emphasis on disease activity and tendency to relapse. A cohort of 105 patients with GPA or MPA and 126 healthy controls (HCs) were included. Clinical and laboratory data were collected for all patients, including disease activity, tendency to relapse, and pharmacological treatment. Using flow cytometry, circulating eosinophils, basophils, neutrophils, and monocytes were assessed. The monocytes were subdivided into classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14-CD16+) monocytes. Mature (CD16high) or newly released (CD16dim) neutrophils were defined, as well as the frequency of CD177+ neutrophils. AAV patients displayed increased frequencies of intermediate monocytes, mature and newly released neutrophils, and an expanded population of CD177+ neutrophils compared to HC. MPA patients differed from GPA patients in terms of lower frequency of classical monocytes. No differences in cell frequencies regarding ANCA phenotype were observed. Paired data from 23 patients demonstrated that active disease was associated with an increased frequency of mature neutrophils and a decreased frequency of monocytes, in particular intermediate monocytes. Moreover, GPA patients with a tendency to relapse displayed an increased frequency of mature neutrophils with increased expression of CD177+. Relapsing MPA patients, on the other hand, showed decreased frequency of intermediate monocytes. Finally, rituximab treatment was associated with increased frequencies of classical and intermediate monocytes. In conclusion, AAV patients exhibit a skewing of different neutrophil and monocyte subpopulations that are associated with disease subtypes, disease activity, rituximab treatment, and propensity to relapse. These changes may contribute to the inflammatory process and could potentially be used as biomarkers for relapse prediction.

Anti-neutrophil cytoplasmic antibody patterns can predict clinical relapse in ANCA-associated vasculitis: overall population and subgroups.

In anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), relapses are cause of concern as they are unpredictable and predictors of poor prognosis. We aimed to assess the characteristic and predictors of clinical relapse in AAV. This retrospective study included 132 cases of AAV newly diagnosed from January 2016 through November 2021 in the Affiliated Hospital of Qingdao University. We reviewed clinical data of patients and analysed the risk factors for clinical relapse of overall population and subgroups by univariate and multivariate regression models and the K-M survival curve was plotted. The rate of relapse was highest in the positive conversion group than the others significantly (p<0.001). In overall population, ANCA patterns (p<0.001; persistent positive pattern: HR=3.352, 95%CI 1.463~7.678, p=0.004; positive conversion pattern: HR=4.760, 95%CI 2.094~10.820, p<0.001) and infections (HR =4.684, 95%CI 1.980~11.079, p<0.001) were significantly associated with clinical relapse. In myeloperoxidase (MPO)-AAV patients, ANCA patterns (p=0.001; persistent positive pattern: HR=4.495, 95%CI 1.508~13.396, p=0.007; positive conversion pattern: HR=7.404, 95%CI 2.652~20.671, p<0.001) and infections (HR=3.594, 95%CI 1.511~8.547, p=0.004) were significantly associated with clinical relapse. In renal involvement patients, ANCA patterns (p=0.004; persistent positive pattern: HR=3.618, 95%CI 1.364~9.592, p=0.01; positive conversion pattern: HR=4.492, 95%CI 1.778~11.352, p<0.001) and infections (HR=7.791, 95%CI 2.511~24.174, p<0.001) were significantly associated with clinical relapse, but were not in patients without renal involvement. Persistently positive and re-positive ANCA and infections predict clinical relapse in AAV, especially in patients with MPO-AAV and renal involvement. Regular ANCA monitoring should be carried out in high-risk populations.

Predicting relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis: a Systematic review and meta-analysis.

ObjectivesRelapses affect 30–50% of patients with ANCA-associated vasculitis (AAV) over 5 years, necessitating long-term treatment. Although there have been studies looking at predictors of relapse in AAV, this research has yet to translate clinically into guidance on tailored therapy. The aim of this systematic review was to identify and meta-analyse existing risk factors from the literature and produce a model to calculate individualised patient risk of relapse.MethodA search strategy was developed to include all studies identifying predictors of AAV relapse using multivariate analysis. Individual risk factors were extracted and pooled hazard ratios (HRs) calculated. A model to predict the time to first relapse based on identified risk factors was tested retrospectively using a cohort of patients with AAV.ResultsThe review of 2674 abstracts identified 117 papers for full text review, with 16 eligible for inclusion. Pooled HRs were calculated from significant risk factors, including anti-PR3 ANCA positivity [HR 1.69 (95% CI 1.46, 1.94)], cardiovascular involvement [HR 1.78 (95% CI 1.26, 2.53)], creatinine >200 µmol/l (relative to creatinine ≤100) [HR 0.39 (95% CI 0.22, 0.69)] and creatinine 101–200 µmol/l [HR 0.81 (95% CI 0.77, 0.85)]. Using data from 182 AAV patients to validate the model gave a C-statistic of 0.61.ConclusionAnti-PR3 ANCA positivity, lower serum creatinine and cardiovascular system involvement are all associated with an increased risk of relapse, and a combination of these risk factors can be used to predict the individualised risk of relapse. In order to produce a clinically useful model to stratify risk, we need to identify more risk factors, with a focus on robust biomarkers.

Ectopic Relapse of Anti-neutrophil Cytoplasmic Antibody-associated Pituitary Vasculitis with No Elevation of Anti-neutrophil Cytoplasmic Antibodies after Renal Remission.

The relationship between anti-neutrophil cytoplasmic antibody (ANCA) titer levels and relapse risk in patients with ANCA-associated vasculitis (AAV) following clinical remission remains controversial. We herein report a case showing ectopic relapse of AAV in the pituitary with no ANCA elevation after renal remission. Magnetic resonance imaging revealed an enlarged pituitary gland. A pituitary biopsy showed geographic necrosis with multinucleated giant cells. We diagnosed this case as relapse of AAV in the pituitary. One month after rituximab therapy, the pituitary gland volume had decreased. The intensification of therapy due to the possibility of vasculitis relapse may facilitate better control of AAV.

Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis

ObjectivesEvaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the...

Prognostic Factors for Survival and Relapse in ANCA-Associated Vasculitis with Renal Involvement: A Clinical Long-Term Follow-Up Study.

Aim We describe the clinical pattern of ANCA-associated vasculitis (AAV) and assess long-term prognostic factors of patients and renal survival and relapse. Methods Data from 85 patients with renal biopsy-proven AAV at a single center with up to 20-year [median 16.2 years (95% CI 14.9-17.7)] follow-up were retrospectively collected. Results Overall, 55% of the patients had microscopic polyangiitis (MPA) and 45% had granulomatosis with polyangiitis (GPA). The histopathological classes were focal in 35%, crescentic in 26%, mixed in 20%, and sclerotic glomerulonephritis in 19% of the patients. As induction treatment, a combination of cyclophosphamide and corticosteroids was given to 82%, while a combination of azathioprine and corticosteroids was maintenance therapy in 79%. The twenty-year patient survival was 45%. In a multivariable analysis, age ≥58 years [hazard ratio (HR) 7.64, 95% CI 3.44-16.95] and myeloperoxidase (MPO) ANCA (HR 2.12, 95% CI 1.08-4.17) were associated with shorter patient survival time. Renal survival was 68% overall: 88% in focal, 71% in crescentic, 56% in mixed, and 37% in sclerotic class (p=0.01). Female sex (HR 0.26, 95% CI 0.10-0.73) was a predictor of improved renal survival, whereas GFR <30 ml/min and MPO-ANCA were associated with worse renal survival (HR 4.10, 95% CI 1.35-12.49 and HR 3.10, 95% CI 1.21-7.95, respectively). Relapse-free survival at 20 years was 10%. MPA was associated with a lower risk for relapse (HR 0.48, 95% CI 0.28–0.82). Conclusion We confirmed the improved patient and renal survival in AAV patients with glomerulonephritis, while relapse remained the primary challenge. Histopathological classification may be relevant for survival.

A PERPLEXING CASE: ANCA-ASSOCIATED VASCULITIS COMPLICATED BY DIFFUSE ALVEOLAR HEMORRHAGE AND THROMBOTIC THROMBOCYTOPENIC PURPURA WITH COMPLETE RESPONSE TO PLASMA EXCHANGE

SESSION TITLE: Pulmonary Vascular Disease SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: The ANCA-associated vasculitides are a group of rare disorders that affect multiple organ systems and can present in a variety of ways, including as diffuse alveolar hemorrhage (DAH). Interestingly, there have also been reports of ANCA-associated vasculitis complicated by thrombotic thrombocytopenic purpura (TTP), although this is only described in case series. Common treatments for vasculitis flares include high-dose steroids plus either rituximab or cyclophosphamide. In severe refractory cases, there may be a role for plasma exchange (PLEX), although confirmation of these results from large trials is still pending. The following patient case illustrates a rare presentation of an ANCA-associated vasculitis flare complicated by DAH and TTP that resolved with PLEX. CASE PRESENTATION: An 82-year-old woman with microscopic polyangiitis presented to our hospital with hemoptysis. On admission, she required 4 liters of oxygen to maintain her saturation above 90%. Labs revealed a hemoglobin of 5.0g/dL and elevated myeloperoxidase (MPO) antibody with positive p-ANCA antibody. A CT of her chest was performed and showed diffuse, bilateral, alveolar infiltrates suggestive of DAH. She was admitted to the intensive care unit (ICU) and started on high dose methylprednisolone plus rituximab while also receiving red blood cells. Over the next two days of her stay, there was significant clinical improvement. However, on hospital day three, she again experienced hemoptysis with increasing oxygen requirements. At the same time, her hemoglobin and platelets both dropped significantly. Hemolysis was suggested by an elevated LDH and bilirubin with decreased haptoglobin. These findings led to further evaluation, which ultimately revealed a decreased ADAMTS13 value consistent with concurrent TTP. Given her worsening clinical status, failure of standard therapies, and development of TTP, the decision was made to start plasma exchange. After two sessions of PLEX, her overall clinical status rapidly improved with rising blood counts coupled with decreasing symptomatology and oxygen requirements. She ultimately finished seven PLEX sessions with complete resolution of her symptoms and has done well on subsequent follow-up. DISCUSSION: This case demonstrates the rare association between ANCA-associated vasculitis and TTP as well as the potential for plasma exchange to treat the co-occurrence of both diseases effectively. In the literature, there have been fewer than 20 case reports of an ANCA-associated vasculitis complicated by DAH and TTP, all of which were successfully treated with PLEX. CONCLUSIONS: In this case, the co-occurrence of TTP and relapse of ANCA-associated vasculitis in a critically ill patient drove the initiation of plasma exchange and ultimately led to rapid clinical improvement. Reference #1: 1. Jordan JM, Manning M, Bates Allen N. Multiple unusual manifestation of Wegener's granulomatosis: breast mass, microangiopathic hemolytic anemia, comsumptive coagulopathy and low erythrocyte sedimentation rate. Arthritis Rheum. 1986;29:1527-31 Reference #2: 2. von Baeyer H. Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies. Ther Apher. 2002;6:320-328. Reference #3: 4. Yamauchi Y, Nagatoya K, Okuno A, Fujii N, Inoue T. Successful treatment for thrombotic thrombocytopenic purpura complicated with myeloperoxidase anti-neutrophil cytoplasmic autoantibody-associated vasculitis. NDT Plus. 2010;3(3):279-281. https://doi.org/10.1093/ndtplus/sfq013. DISCLOSURES: No relevant relationships by Timothy Dempsey, source=Web Response No relevant relationships by Patricio Escalante, source=Web Response No relevant relationships by Tobias Peikert, source=Web Response

Renal relapse in antineutrophil cytoplasmic autoantibody-associated vasculitis: unpredictable, but predictive of renal outcome.

To determine predictors of renal relapse and end-stage renal failure (ESRF) in patients with ANCA-associated vasculitis. Data from four European Vasculitis Society randomized controlled trials, conducted roughly simultaneously between 15 March 1995 and 30 September 2002, was pooled to determine predictors of long-term renal outcome. The respective trial inclusion criteria covered the entire spectrum of disease severity. Baseline predictors of time to first renal relapse and time to ESRF were assessed by competing events analysis and Cox proportional hazards regression. The effect of renal relapse on time to ESRF was assessed by adding renal relapses to the competing events analysis as a time-varying covariate. The number of patients participating was 535; mean serum creatinine (±s.d.) at entry was 341 ± 321 µmol/l and 19.7% developed ESRF. One or more renal relapse(s) was experienced by 101 patients. Multivariable regression analysis demonstrated that, in addition to impaired baseline renal function, developing ⩾1 renal relapse was an independent risk factor for ESRF (subhazard ratio 9; 95% CI 4, 19; P < 0.001). No predictive factors for renal relapse were found. In addition to baseline renal function, the occurrence of renal relapses is an important determinant of ESRF in patients with ANCA-associated vasculitis. We did not find any clinical predictors for renal relapse itself, including disease activity elsewhere. In light of the silent nature of renal relapse in ANCA-associated vasculitis, we stress the need for long-term vigilant monitoring for early signs of renal relapse and propose performing 3-monthly urinalysis. This will enable timely treatment and help further improve renal outcome.

The Utility of Urinalysis in Determining the Risk of Renal Relapse in ANCA-Associated Vasculitis.

The significance of persistent hematuria or proteinuria in patients with ANCA-associated vasculitis who are otherwise in clinical remission is unclear. A post hoc analysis was conducted using participants enrolled in two randomized, placebo-controlled clinical trials who had active GN due to ANCA-associated vasculitis, had positive ANCA, and achieved remission by month 6. Dipstick and microscopic urinalyses were performed at each visit. Persistent hematuria or proteinuria for at least 6 months and the cumulative duration of hematuria were examined. Renal relapse was defined as new or worsening red blood cell casts and/or worsening kidney function according to the Birmingham Vasculitis Activity Score for Granulomatosis with Polyangiitis. There were 149 patients included in this study: 42% had persistent hematuria, and 43% had persistent proteinuria beyond 6 months. Persistent hematuria was associated with a significantly higher risk of relapse, even after adjusting for potential confounders (subdistribution hazard ratio, 3.99; 95% confidence interval, 1.20 to 13.25; P=0.02); persistent proteinuria was not associated with renal relapse (subdistribution hazard ratio, 1.44; 95% confidence interval, 0.47 to 4.42; P=0.53). Furthermore, greater cumulative duration of hematuria was significantly associated with a higher risk of renal relapse (adjusted subdistribution hazard ratio, 1.08 per each month; 95% confidence interval, 1.03 to 1.12; P<0.01). The median time to renal relapse was 22 months. In patients with ANCA-associated vasculitis and kidney involvement who achieve remission after induction therapy, the presence of persistent hematuria, but not proteinuria, is a significant predictor of future renal relapse.

Delta Neutrophil Index Is Associated with Vasculitis Activity and Risk of Relapse in ANCA-Associated Vasculitis.

PurposeDelta neutrophil index (DNI) represents the immature granulocytes count associated with neutrophil-consumption. We investigated whether DNI might be associated with Birmingham vasculitis activity score (BVAS) at diagnosis and could predict relapse during the follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).Materials and MethodsWe reviewed the medical records of 97 patients having DNI results. Twenty patients had granulomatosis with polyangiitis (GPA), 58 had microscopic polyangiitis (MPA), and 19 had eosinophilic GPA (EGPA). We collected clinical and laboratory data including BVAS, five factor score (FFS), and DNI. The correlation coefficient and cumulative relapse free survival rate were obtained. The optimal cut-off of DNI was extrapolated by calculating the area under the receiver operator characteristic curve.ResultsDNI was significantly related to cross-sectional BVAS. Furthermore, among continuous variables, only DNI could reflect BVAS of GPA and MPA, but not EGPA. Severe AAV was defined as BVAS ≥20 (the highest quartile). At diagnosis, patients having DNI ≥0.65% had a significantly higher risk of severe GPA and MPA than those having not (relative risk 4.255) at diagnosis. During the follow-up, DNI ≥0.65% could predict the higher relapse rate.ConclusionDNI could reflect BVAS at diagnosis and furthermore, DNI ≥0.65% could not only identify severe AAV at diagnosis, but also predict relapse during the follow-up in patients with GPA and MPA.

Risks and Benefits of Glucocorticoids in ANCA-Associated Vasculitis

Purpose of Review Glucocorticoids are a cornerstone in the treatment of ANCA-associated vasculitis. However, the role of long-term, low-dose glucocorticoids for the prevention of relapses is uncertain and substantial practice pattern variation exists. In this review, we will explore evidence supporting or refuting the position that low-dose glucocorticoids modify the risk of relapse in ANCA-associated vasculitis. Recent findings Basic experimental studies suggest glucocorticoids could modify the course of ANCA-associated vasculitis and clinical studies suggest patients treated with longer courses of glucocorticoids are free of relapse for longer periods than patients treated with shorter courses. Some studies, however, are conflicting. Summary There continues to be a dearth of high quality evidence addressing the use of low-dose glucocorticoids in ANCA-associated vasculitis. Although ongoing trials will help inform this fundamental treatment question, large, high-quality trials are needed.

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.

Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild–moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray’s regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8–14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray’s model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different.

Repeat cycles of rituximab on clinical relapse in ANCA-associated vasculitis: identifying B cell biomarkers for relapse to guide retreatment decisions

ObjectiveTo assess clinical and B cell biomarkers to predict relapse after rituximab in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) using retreatment on clinical relapse strategy.Methods35 patients with AAV received treatment...

Metabolic syndrome in ANCA-associated vasculitis

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors and a major cause of morbidity and mortality in the western world. Despite the fact that cardiovascular diseases are a major cause of mortality in patients with ANCA-associated vasculitis (AAV), the relationship between MetS and AAV has not yet been explored. Thus it is the aim of this study to investigate the prevalence of MetS within a cohort of patients with AAV and to assess whether MetS in AAV is associated with a pro-inflammatory state. Ninety-one patients with AAV were compared with 89 healthy controls (HCs) in a cross-sectional study. Both groups underwent anthropometric measures and laboratory tests to determine the prevalence of MetS in accordance with the National Cholesterol Education Program Adults Treatment Panel III (NCEP-ATP-III) definitions. Furthermore, the clinical course of AAV was related to the occurrence of MetS. Within the AAV patient group, 39 (43%) fulfilled the NCEP-ATP-III criteria for MetS compared with 22 (25%) of the controls (P = 0.012). This difference in prevalence could not be explained by current or cumulative prednisone use in patients with AAV. Among patients with AAV, the presence of MetS was significantly associated with increased levels of CRP and neopterin. Finally, the relapse rate was higher in patients with MetS as compared with those without MetS. The prevalence of MetS is significantly increased in AAV. MetS is associated with a more pro-inflammatory state in AAV and might increase the risk of developing a relapse of AAV.

Reduced number of endothelial progenitor cells is predictive of early relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis

ANCA-associated vasculitis (AAV) is an inflammatory disorder of small- to medium-sized vessels with relapsing/remitting progression. Microvascular endothelial injury is a major feature of AAV. Circulating endothelial progenitor cells (EPCs) may provide an endogenous repair mechanism to counteract ongoing endothelial damage. We hypothesized that decreased capacity for endothelial regeneration paralleled by low EPC numbers could increase the risk of relapse in patients with AAV. The number of circulating EPCs was determined by a colony-forming assay in a cohort of 41 patients with AAV. The patients were stratified into three subgroups according to the initial EPC count (low, medium and high) and prospectively followed. The primary goal was to determine the association between baseline EPC level and the time to the first relapse of the disease. A total of 19 (46%) patients relapsed during the study period. The cumulative relapse-free survival increased stepwise across three increasing baseline levels of EPCs (P = 0.013). EPC levels were not predictive of progression of renal disease, number of organs involved or death from any cause. Low numbers of EPCs are associated with increased propensity for early relapse of AAV.

Venous thromboembolism in ANCA-associated vasculitis--incidence and risk factors

In patients with ANCA-associated vasculitis (AAV), an increased incidence of venous thromboembolism (VTE), mainly during active disease, has been described. In a large cohort of AAV patients, we assessed the incidence of VTE and its relation with disease activity and classic risk factors for VTE. Patients newly diagnosed with AAV between 1990 and 2005 and treated with cyclophosphamide and corticosteroids were included. Data were retrospectively retrieved from charts and by questionnaire. The incidence of VTE associated with and following a diagnosis of AAV was calculated (VTE/100 person-years) and related to periods with active disease. One hundred and ninety-eight patients with AAV were followed for 6.1 (0.2-17.6) yrs. In 23 patients (12%), 25 VTEs (17 deep venous thromboses, 3 pulmonary emboli, 5 both) occurred in association with AAV, of which 52% occurred during active disease, defined as 3 months before and after diagnosis or relapse of AAV. Overall, VTE incidence was 1.8/100 person-years, increasing to 6.7/100 during active disease. VTEs occurred significantly less frequently in patients with WG than in patients with microscopic polyangiitis and renal limited vasculitis. Classic risk factors were present in most patients at some moment during follow-up. There were no significant differences in classic risk factors between patients with and without AAV-associated VTE. Patients with AAV have an increased risk of developing VTEs, especially when AAV is active. This finding could not be explained by classic risk factors, but is probably related to endothelial changes and hypercoagulability induced by AAV and its therapy.

Prolonged Treatment with Low-Dose Intravenous Pulse Cyclophosphamide May Reduce Rate of Relapse in ANCA-Associated Vasculitis

Background: Cyclophosphamide has transformed the outcome of ANCA-associated vasculitis, but it is highly toxic. Recent studies have suggested that pulsed intravenous cyclophosphamide (pCyc) is an effective alternative with less complications, but may lead to an increased rate of relapse. However, these studies used relatively short courses of treatment with cyclophosphamide. In this study we used a prolonged course of low-dose intravenous cyclophosphamide for 18–24 months for ANCA-associated vasculitis, evaluated the effectiveness of pCyc and analysed the outcome of a prolonged treatment on the rate of relapse. Methods: A retrospective analysis of all the patients treated with pCyc from 1995 to 2002 was performed. Results: Thirty-seven patients were followed for an average of 38 months. Thirty-four of 37 patients (91.9%) achieved complete remission at 3 months. Eight (21%) episodes of relapse occurred in 7 patients. The cyclophosphamide was well tolerated with a low rate of infections (18.9%) and 1 death (2.7%) due to sepsis whilst on cyclophosphamide. Conclusion: In this study, pCyc was effective in achieving rapid remission and had a low complication rate. If prolonged, this treatment may reduce the rate of relapse.

Outcome of patients with antineutrophil cytoplasmic autoantibody—associated vasculitis following cadaveric kidney transplantation

In this retrospective study, we report on the progress of eight patients with biopsy-proven systemic vasculitis following cadaveric renal transplantation. Extrarenal manifestations associated with antineutrophil cytoplasmic autoantibodies (ANCAs) were present in all but one case. All the patients were on cyclosporine A-based immunosuppression, and none of them had active disease at transplantation. The mean time from the last episode of vasculitis to transplantation was 46 months (range, 10 to 132 months). On the day of transplantation, all but one patient had detectable ANCAs, which ranged from 1:100 to 1:2,000 (perinuclear ANCAs [P-ANCAs], four patients; cytoplasmic ANCAs [C-ANCAs], three patients). There were three patients with Wegener's granulomatosis, none of whom relapsed. Of those patients with microscopic polyangiitis (P-ANCAs, three patients; C-ANCAs, two patients), only one presented with relapse episodes after transplantation; the episodes involved the lungs and the kidney graft, and were successfully treated by methylprednisolone pulses. This patient had the highest ANCA titer before (1: 2,000) and after (up to 1: 10,000) grafting, and received no immunosuppression prior to transplantation since vasculitis was diagnosed after she had developed end-stage renal failure. This study shows that a relapse of ANCA-associated vasculitis following successful cadaveric renal transplantation occurs infrequently in the cyclosporine A era (ie, 12%), despite the persistence of circulating ANCAs in these patients at the time of transplantation, and even afterward in some cases.