Biomedical subjects
Publications and source records attributed to L Guillevin.
Wegener's syndrome is a granulomatous angiitis with peri or extra-vascular granulomas. The complete form, includes glomerulopathy, pulmonary signs and lesions of the face. Prognosis improved with corticosteroids and immunosuppressors although appropriate administration modalities are still under debate.
OBJECTIVE: To test the effectiveness and tolerance of antiviral agents associated with short term immunosuppression in the treatment of polyarteritis nodosa (PAN) related to hepatitis B virus (HBV). METHODS: We conducted a prospective, nonblinded, multicenter trial in which patients with multisystemic PAN related to HBV were included. Every patient initially underwent a short term (2 weeks) treatment with prednisone and then received vidarabine (Vira A) and plasma exchanges. The end point of the study was control of the disease (recovery or remission) or death. RESULTS: Thirty-three patients were included. Every patient had histopathologic or arteriographic evidence of vasculitis and was infected with actively replicating HBV. Disease activity during the first 6 months was controlled in 26 patients (78.8%). Among the 25 patients still alive at the end of the study, 24 (72.7%) had completely recovered with no clinical or laboratory evidence of systemic vasculitis after at least 18 months without treatment. Eight patients died during the study period; 3 of treatment failure, usually early in the course of the disease. One patient died of fulminant hepatitis 3 months after the entry in the study at time of seroconversion. The survival curve showed that at 7 years, 76% of the patients were alive. HBeAg/anti-HBeAb seroconversion was observed in 12 patients (36.3%) after one Vira A cycle. When a 2nd cycle of Vira A or alpha interferon was prescribed, HBeAg/anti-HBeAg seroconversion occurred in 15 patients (45.4%). Two other patients who underwent a 2nd cycle of Vira A administration, had lost HBeAg and no longer expressed serological evidence of replication as assessed by HBV DNA spot hybridization. At the end of the study, 17 (51.5%) no longer expressed serological evidence of HBV replication. This treatment was effective and only minor side effects were noted. CONCLUSIONS: We conclude that this new therapeutic approach to PAN related to HBV effectively controlled systemic vasculitis and was associated with a higher number of recoveries from chronic HBV infections. The development of new antiviral agents, such as interferon alpha 2b, allows us to hope that antiviral therapy will have a role to play as a first line treatment regimen of virus induced vasculitis.
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Congenital heart blocks due to immunological causes are rare. A case is reported of a fetus with auriculo-ventricular block diagnosed at 22 weeks of amenorrhoea and intrauterine death at 32 weeks. The authors discussing the case find the most likely link: an anti-RO (SS-A) and anti-LA (SS-B) immunological block and they suggest that there are minor localised lesions in the nodal tissue which gives rise to benign disturbances of cardiac rhythm and they point out ways of preventing intrauterine auriculo-ventricular block.
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The sporadic observation of pneumocystosis in patients suffering from systemic diseases led us to investigate the role of treatment-induced lymphopenia, affecting in particular CD4 cells. We report the results of a retrospective study on 16 patients in whom infectious complications were sought and correlated with the number of lymphocytes.
OBJECTIVE: To define the most effective treatment for polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS). METHODS: We conducted a prospective, randomized, multicenter trial in which 78 patients were randomly assigned to receive either prednisone and plasma exchange (group A; n = 36) or prednisone alone (group B; n = 42) as first-line treatment of PAN and CSS. Patients with hepatitis B virus-related PAN were not included in this study. The end point of the study was control of the disease (recovery and remission) or death. RESULTS: Clinical symptoms and laboratory findings did not differ statistically in the 2 groups at study entry. Initial control of the disease was similar in both groups. The assigned treatment was stopped in 16 patients because of lack of efficacy. Oral cyclophosphamide or dapsone therapy reversed the disease evolution in 7 of these 10 group A patients and in 4 of these 6 group B patients. At 7 years of followup, 56 patients had completely recovered (27 in group A, 29 in group B), 7 patients were in clinical remission, and 15 patients had died (19.2%; 6 group A patients and 9 group B patients). The prednisone-plasma exchange combination was no more beneficial than corticosteroids alone in preventing relapses over the long term. There was no significant difference in the 7-year cumulative survival rates of the two groups (83% and 79%, respectively). CONCLUSION: Based on our data, we conclude that combined treatment with prednisone and plasma exchange is not superior to treatment with prednisone alone and must not be systematically employed for initial treatment of PAN and CSS. In most cases, cyclophosphamide as second-line treatment is effective and well tolerated.
The pharmacokinetics of vidarabine were studied in 8 patients with polyarteritis nodosa related to hepatitis B virus infection. The drug was administered by continuous infusion for three weeks at doses of 15 (1 week) and 7.5 (2 weeks) mg/kg per day, during which time 15 plasma exchanges were performed. Plasma was assayed for vidarabine and its principal metabolite, hypoxanthine arabinoside by high pressure liquid chromatography. Vidarabine was not detected in the plasma of any patients. Hypoxanthine arabinoside levels were used to evaluate vidarabine kinetics. The serum levels of hypoxanthine arabinoside ranged from 3.6 to 21.5 mg/l. The mean elimination half-life (+/- SD) was 3.0 +/- 1.7 h. The plasma clearance (mean +/- SD) was 195 +/- 270 ml/min when the dose was 7.5 mg/kg per day and 66.3 +/- 47 ml/min for a 15 mg/kg per day/dose (NS). Except for the elimination half-life, these results were not fully consistent with those observed in other studies. The influence of multiple plasma exchanges on vidarabine kinetics is limited and dosage adjustment is not required based on the continuous infusion of vidarabine.
The clinical and pathological features of a patient with giant cell arteritis of the uterus and ovaries are described. A 61 year old woman had fever and weight loss over a period of eight months. A hysterectomy with bilateral salpingo-oophorectomy was performed for a large cystic ovarian mass. Histological examination showed a benign ovarian cyst and unexpected giant cell arteritis affecting numerous small to medium sized arteries in the ovaries and myometrium. The diagnosis of temporal arteritis was confirmed by a random temporal artery biopsy, despite the absence of symptoms of temporal arteritis. This observation is compared with previously reported cases and the relation between granulomatous arteritis of the genital tract and temporal arteritis is discussed. The main differential diagnosis in this localisation was represented by Wegener's granulomatosis and periarteritis nodosa.
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To define the most effective treatment for polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS), we undertook 3 consecutive prospective therapeutic trials including 182 patients and tried to answer several important questions: should cyclophosphamide (CYC) be given as the first-line treatment? what is the place of plasma exchanges (PE) in the treatment of systemic vasculitis? does hepatitis B virus (HBV)-related PAN require specific treatment? Our first randomized trial in 71 patients compared the association of CYC with corticosteroids (CS) and PE to CS and PE, in order to evaluate the efficacy of CYC given as the first-line treatment to control disease activity and subsequent survival of PAN and CSS patients. Between December, 1983, and December, 1988, we conducted two trials simultaneously: one aimed at patients without HBV markers and the second at patients with HBV markers. In 78 patients without HBV markers, we compared prednisone and PE to prednisone alone as the initial therapeutic regimen. In 33 patients with PAN related to HBV, a new therapeutic strategy was applied as an alternative to long-term steroid and immunosuppressive therapy: short-term steroid therapy and PE were used to control the evolution of PAN and anti-viral therapy was administered to suppress the etiological agent of the vasculitis. Twelve years after the beginning of the trials on PAN and CSS patients, we think that the therapeutic strategy should be as follow: in PAN without HBV and CSS: Prednisone in association with CYC improves the control of the disease despite infectious side effects which may be reduced by better CYC dose adaptation. It is also possible that CYC could be more effective in some subgroups of PAN, for instance those with clinical symptoms of poor prognosis. We are presently attempting to optimize the CYC prescription (pulses of CYC) in PAN and CSS in the hope of improving prognosis; in PAN related to HBV: The first-line treatment should be the association of anti-viral agents and PE. This treatment was effective and cured a majority of patients within 2 to 3 months; half of them seroconverted. The length of HBV infection before its diagnosis, delay before initiation of treatment and previous immunosuppressive therapy led to a poor seroconversion rate; the role of PE in the treatment of systemic necrotizing angiitis: PE are obviously useful in PAN related to HBV where immune complex deposition has been demonstrated.(ABSTRACT TRUNCATED AT 400 WORDS)
In an attempt to establish the characteristics, circumstances leading to infection and development of polyarteritis nodosa (PN) related to hepatitis B virus (HBV), prognostic factors and outcome, and to define the most effective treatment, 66 patients observed between 1972 and 1989 were analyzed. Hepatitis was clinically present in 19/66 patients before PN. In most cases, PN occurred less than 6 months after infection. Clinical manifestations of PN were comparable to those observed in patients without HBV infection except for orchitis which was present in 13.6% and for pulmonary signs which were absent. Transaminases were normal in 38 cases for SGOT and 31 for SGPT and twice the normal range or more in the other cases. Antineutrophil cytoplasmic antibodies (ANCA) were tested in 22 patients and present in 2 (9%). Twenty-eight patients were treated with prednisone +/- oral cyclophosphamide +/- plasma exchanges. Thirty-eight patients were given a short-term treatment with prednisone followed by the association of vidarabine, 15 mg/kg bw/d for one week and 7.5 mg/kg bw/d for 2 weeks, and plasma exchanges: 14 sessions during the 3 weeks of vidarabine infusion, then tapered until stopping treatment after 2 to 3 months depending upon the clinical results obtained. The mean duration of follow-up was 50.3 +/- 46.1 months. At the end of follow-up, 13 of the 28 patients (46.4%) treated with steroids +/- cyclophosphamide +/- plasma exchanges died and 7/38 (18.4%) of those treated with vidarabine and plasma exchanges (p < 0.001) died. HBe/anti-HBe seroconversion was observed in 2 patients treated with prednisone +/- cyclophosphamide +/- plasma exchanges who were alive at the time of final analysis and in 16 patients receiving the other regimen. The outcome of patients treated with a few days of prednisone, vidarabine and plasma exchange was good and, therefore, we propose this protocol as the first viable treatment for polyarteritis nodosa related to HBV, surpassing the conventional treatment with steroids and cyclophosphamide, which stimulates viral replication.
We report on a case of acute renal failure secondary to relapse of a centrocytocentroblastic non-Hodgkin's lymphoma. Twenty-seven cases of acute renal failure due to lymphomatous infiltration of the kidneys have been so far reported. The clinical presentation is non-specific; the size of the kidneys appears normal or enlarged; diagnosis is confirmed by renal biopsy and/or CT scan examination. Chemotherapy and/or radiotherapy sometimes lead to dramatic improvement of renal function. However, prognosis is poor, mostly due to lymphomatous evolution.
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