OBJECTIVES:To analyse the 10-year outcomes of 64 patients with non-HBV polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA) and Five-Factor Score-defined poor-prognosis factors enrolled (1994-2000) in the prospective, randomised, open-label CHUSPAN trial.METHODS:The 64 patients were randomised to receive 12 (33: 23 MPA, 10 PAN) or 6 (31: 17 MPA, 14 PAN) cyclophosphamide (CYC) pulses combined with glucocorticoids. Ten-year follow-up of these patients included times to relapse(s), failure(s) and/or deaths calculated from treatment onset. Data were censored after 120 months of follow-up.RESULTS:Eleven patients were lost to-follow-up (mean±SD follow-up: 61.9±35.2 months), with no between-group difference. As previously reported, baseline clinical characteristics and laboratory values were comparable for the 2 groups. After induction, 53/64 (83%) entered remission, with comparable percentages for both groups. The regimen was intensified for 11 initial non-responders: 4 achieved remission and 8 died before doing so. During extended follow-up, 26 patients experienced ≥1 relapse(s): 12 in the 12-pulse group and 14 in the 6-pulse group (p=0.47). At 10 years, overall and disease-free survival rates were 57.4% and 29.9%, with no between-group differences (p=0.185 and p=0.367, respectively). Factors associated with shorter disease-free survival were age ≥65 years and alveolar haemorrhage at diagnosis.CONCLUSIONS:Although the 3-year CHUSPAN trial results indicated the superiority of 12 vs. 6 CYC pulses, that early advantage progressively declined and became non-significant by 10 years.

OBJECTIVES:To describe the prevalence, characteristics, and outcome of cutaneous ischemia, and whether it can occur in systemic necrotizing vasculitides (SNVs), i.e., polyarteritis nodosa, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis. METHODS:We conducted a retrospective analysis of all patients with SNV who were included in the French Vasculitis Study Group cohort database between March 1963 and September 2007. We compared characteristics and outcomes for patients with and without cutaneous ischemia (digital necrosis and/or isolated necrotic cutaneous ulcers). RESULTS:Among the 1304 patients with a diagnosis of SNVs, 40 (3.1%) had digital necrosis and 25 (1.9%) had isolated necrotic cutaneous ulcers, with an equal distribution among SNVs. Presence of cutaneous ischemia was associated with past and/or current smoking [odds ratio (OR), 1.73; 95% confidence interval (95% CI), 1.02-2.95] and history of coronary artery disease (2.40; 1.01-6.00), as well as with other cutaneous manifestations (6.54; 3.21-8.67), gastrointestinal tract perforations (4.29; 1.41-13.07), and arthralgias (1.84; 1.10-3.07) during diagnosis. Ten patients with digital necrosis underwent extremity amputation, but no patient with isolated necrotic cutaneous ulcers (p = 0.007) underwent it. Smoking was the main risk factor of amputation (OR, 9.1; 1.7-48.9). At a mean follow-up of 10 years, cutaneous ischemia was identified as an independent predictor of vasculitis relapse (hazard ratio, 1.47; 95% CI, 1.05-2.05) and all-cause death (1.66; 1.01-2.74). CONCLUSIONS:Cutaneous ischemia is a rare manifestation of SNVs but is associated with an increased risk of relapse and mortality. Tobacco use is associated with amputation, which emphasizes the importance of managing conventional cardiovascular risk factors in SNV patients.

The antiviral molecule acyclovir can be responsible of severe renal dysfunction. Intratubular crystal precipitation of the drug may represent a major pathogenetic mechanism.Observation. - A 30-year old, immunocompetent woman was admitted in the neurology unit for a viral meningo-encephalitic syndrome. Intravenous acyclovir was delivered at the close of 45 mg/kg per day. Despite a neurological improvement, she developed an acute renal insufficiency with the serum creatinine increasing from 63 to 385 mu mol/L within 12 days. The urine study revealed great amounts of birefringent crystals which were typical of acyclovir derived crystals according to the spectrophotometric examination. Withdrawal of acyclovir treatment in combination with oral and parenteral hydration resulted in a complete recovery of the renal function. The conditions favouring acyclovir-induced nephrotoxicity are discussed. (C) 2009 Association Societe de nephrologie. Published by Elsevier Masson SAS. All rights reserved.

Objective. Because the optimal cyclophosphamide (CY) treatment duration for severe polyarteritis nodosa (PAN) without vir-us infection and microscopic polyangiitis (MPA) has not been established, we conducted a trial to compare the effectiveness of 6 versus 12 CY pulses given in combination with corticosteroids (CS).Methods. Sixty-five (18 PAN, 47 MPA) previously untreated patients were randomized to receive 12 (n = 34) or 6 (n 31) CY pulses combined with CS. PAN and MPA were histologically proven or met ACR criteria. All patients presented greater than or equal to1 factor of severity according to the five factor score (FFS). CY pulses were administered every 2 weeks for 1 month, then every 4 weeks. The end point of the study was the number of events (relapses and/or deaths) occurring in each group, analyzed according to an intention-to-treat strategy. The outcome was evaluated by Cox proportional hazards analysis.Results. The baseline characteristics were similar for both groups. The mean (+/- SD) followup was 32 +/- 21 months. Survival analysis showed a significantly lower relapse probability (P = 0.02; hazards ratio [HR] = 0.34) and higher event-free survival (P = 0.02, HR = 0.44) for the 12 CY-pulse group while the mortality rates were not significantly different (P = 0.47).Conclusion. These results suggest that 6 CY pulses are less effective than 12 CY pulses to treat severe PAN and MPA, particularly with respect to the risk of relapses.