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[静脉输注环磷酰胺治疗急性系统性红斑狼疮。价值与局限性]

[Treatment of acute systemic lupus erythematosus with intravenous infusions of cyclophosphamide. Value and limitations].

作者信息

De Bandt M, Goycochea M V, Meyer O, Delahousse M, Palazzo E, M'Bappé P, Kahn M F

机构信息

Service de Rhumatologie, Hôpital Bichat, Paris.

出版信息

Ann Med Interne (Paris). 1994;145(2):75-87.

PMID:8024184
Abstract

Monthly intravenous cyclophosphamide (IVCY) has been a recommended therapy for severe lupus nephritis or neurological flare-ups in lupus patients. But the optimal treatment regimen and duration remains unknown. We report our experience in an open study of 37 patients treated with monthly IVCY. Thirty-four women and 3 men, mean age 35.5 with a mean disease duration of 59 months, with a mean 5.7 ACR criteria for SLE were analysed. 27 (group I) had lupus nephritis (OMS Class III or IV) and 10 had neurological involvement (group II). In group I, after six months of IVCY, a significant improvement was noticed in the UCH-Middlesex clinical index (2.9 pts vs 7.8), the proteinuria (3.12 g/d vs 5.4), complement and split fractions (CH50 98.4 vs 48.9%; C3 877 vs 600 mg/l; C4 177 vs 128 mg/l), the level of anti-DNA antibodies (67.5 vs 775 UI/ml) and the daily dose of steroids (22 vs 44 mg/d). Kidney biopsies showed a reduction of the activity index despite a slight increase of the chronicity index (4.1 vs 6.3 pts and 5.5 vs 3.6 pts). Those results were not maintained at medium and long term. Moreover five patients presented with worsening of renal function during IVCY treatment and two patients relapsed after the end of the treatment. In group II significant improvement was noticed at six months concerning the clinical index (1.77 pts vs 7.17) and the daily dose of steroids, 3 patients died because of cerebral vasculitis refractory to IVCY. Adverse effects are frequent: infectious (25 among 20 patients), hemorrhagic cystitis (2 events in 1 patient), gastrointestinal side effects were common (12/37 patients). Were also noticed: neutropenia (5/37), transient amenorrhea (4/28), drug induced menopausis (2/28). Overall mortality is important (7/37), uneffectiveness of IVCY was noticed in 5 patients, flares occurred in 8 patient during or after stopping treatment. IVCY seems efficacious if given at the very beginning of the flare. Its usefulness is obvious at six months among clinical and biological data in patients with severe lupus nephritis or neurological flare. It seems that long term outcome on the renal function is not modified.

摘要

每月静脉注射环磷酰胺(IVCY)一直是狼疮患者严重狼疮性肾炎或神经发作的推荐治疗方法。但最佳治疗方案和疗程仍不清楚。我们报告了对37例接受每月IVCY治疗的患者进行的一项开放性研究的经验。分析了34名女性和3名男性,平均年龄35.5岁,平均病程59个月,平均符合5.7项美国风湿病学会(ACR)SLE标准。27例(第一组)患有狼疮性肾炎(世界卫生组织(OMS)III或IV级),10例有神经受累(第二组)。在第一组中,IVCY治疗6个月后,UCH-米德尔塞克斯临床指数(2.9分对7.8分)、蛋白尿(3.12g/天对5.4g/天)、补体及裂解片段(CH50 98.4对48.9%;C3 877对600mg/l;C4 177对128mg/l)、抗DNA抗体水平(67.5对775UI/ml)和类固醇日剂量(22对44mg/天)有显著改善。肾活检显示活动指数降低,尽管慢性指数略有增加(4.1对6.3分和5.5对3.6分)。这些结果在中长期未得到维持。此外,5例患者在IVCY治疗期间肾功能恶化,2例患者在治疗结束后复发。在第二组中,6个月时临床指数(1.77分对7.17分)和类固醇日剂量有显著改善,3例患者因对IVCY难治的脑血管炎死亡。不良反应常见:感染(20例患者中有25例)、出血性膀胱炎(1例患者发生2次)、胃肠道副作用常见(12/37例患者)。还注意到:中性粒细胞减少(5/37)、短暂性闭经(4/28)、药物性绝经(2/28)。总体死亡率较高(7/37),5例患者IVCY无效,8例患者在治疗期间或停药后发作。如果在发作刚开始时给予IVCY似乎有效。在严重狼疮性肾炎或神经发作患者的临床和生物学数据中,其在6个月时的有效性是明显的。似乎对肾功能的长期结果没有改变。

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