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柳氮磺胺吡啶治疗盘状红斑狼疮:11例报告

[Treatment of discoid lupus erythematosus with sulfasalazine: 11 cases].

作者信息

Delaporte E, Catteau B, Sabbagh N, Gosselin P, Breuillard F, Doutre M S, Broly F, Piette F, Bergoend H

机构信息

Service de Dermatologie A, Hôpital Claude-Haried, CHRU, Lille.

出版信息

Ann Dermatol Venereol. 1997;124(2):151-6.

PMID:9740825
Abstract

INTRODUCTION

Antimalaria agents and thalidomide are two reference drugs for discoid lupus erythematosus. In non-responders or after secondary resistance or contraindications, there are a number of alternative therapeutics which are less effective and more toxic. We therefore conducted an open study in patients with discoid lupus erythematosus treated with sulfasalazine.

PATIENTS AND METHODS

Seven men and four women (mean age 40 years) with severe discoid lupus erythematosus (mean duration of disease 14 years) were treated with sulfasalazine (2 g/d). This treatment was initiated after a previous failure or contraindication of antimalarial drugs or thalidomide. The acetylation phenotype was predicted in all patients with N-acetyltransferase 2 genotyping. Genome DNA was tested for mutations causing an N-acetyltransferase deficiency. Homozygous individuals or those with heterozygous composites for the tested mutations were predicted slow acetylators and those with a homozygous or heterozygous genotype for an allele carrying a normal sequence at the mutation sites were predicted rapid acetylators.

RESULTS

We had 7 complete responses, 1 partial response and 3 failures. Mean delay to efficacy was 7 weeks, longer for lesions involving the scalp (4 to 5 months). Six of the 8 responders were given sulfasalazine exclusively. The effect was suspensive and dose-dependent; the minimal effective dose was 1.5 g/d. Excepting light sensitization requiring discontinuation, there were no clinically significant side effects. Neutropenia occurred in one patient and moderate and transient live enzyme movements did not require treatment withdrawal. The only immunoallergic side effect (light sensitization) observed occurred in a slow acetylator. All responders except one were rapid acetylators.

DISCUSSION

Salazosulfapyridine, or sulfasalazine, is composed of a derivative of 5-aminosalicylic acid and a sulfamide fraction, sulfapyridine. It is only marginally used in dermatology except for psoriasis. Its efficacy in chronic lupus erythematosus has been reported in one case. We confirmed the role of this compound in the treatment of chronic lupus erythematosus. The rare observations of induced lupus and development of antinuclear antibodies are not a contraindication, but require close regular clinical and biological surveillance. The potential risk is that possible hypersensitivity could lead to reserving sulfasalazine for severe resistant chronic lupus erythematosus after failure with antimalarials and thalidomide. Nevertheless, our study demonstrates that the slow acetylator phenotype predicts immunoallergic events, as observed by other authors, and would be a factor predicting nonresponse. If these results are confirmed by other studies, it would be possible to propose sulfasalazine as a treatment for discoid lupus erythematosus in rapid acetylators.

摘要

引言

抗疟药和沙利度胺是盘状红斑狼疮的两种参考药物。对于无反应者、继发耐药或存在禁忌证的患者,有许多疗效较差且毒性更大的替代疗法。因此,我们对接受柳氮磺胺吡啶治疗的盘状红斑狼疮患者进行了一项开放性研究。

患者与方法

7名男性和4名女性(平均年龄40岁)患有重度盘状红斑狼疮(平均病程14年),接受柳氮磺胺吡啶治疗(2克/天)。此前抗疟药或沙利度胺治疗失败或存在禁忌证后开始此治疗。对所有患者进行N - 乙酰转移酶2基因分型以预测乙酰化表型。检测基因组DNA中导致N - 乙酰转移酶缺乏的突变。检测突变的纯合个体或杂合组合个体被预测为慢乙酰化者,突变位点携带正常序列等位基因的纯合或杂合基因型个体被预测为快乙酰化者。

结果

我们有7例完全缓解、1例部分缓解和3例治疗失败。起效的平均延迟时间为7周,累及头皮的皮损起效时间更长(4至5个月)。8例缓解患者中有6例仅接受柳氮磺胺吡啶治疗。疗效具有持续性且呈剂量依赖性;最小有效剂量为1.5克/天。除因光敏感需停药外,无具有临床意义的副作用。1例患者出现中性粒细胞减少,中度且短暂的肝酶波动无需停药。观察到的唯一免疫过敏副作用(光敏感)发生在一名慢乙酰化者身上。除1例患者外,所有缓解者均为快乙酰化者。

讨论

柳氮磺吡啶,即柳氮磺胺吡啶,由5 - 氨基水杨酸衍生物和磺胺吡啶组成。除银屑病外,它在皮肤科的应用较少。其在慢性红斑狼疮中的疗效曾有过1例报道。我们证实了该化合物在慢性红斑狼疮治疗中的作用。罕见的药物性狼疮及抗核抗体产生并非禁忌证,但需要密切定期进行临床和生物学监测。潜在风险在于可能的超敏反应可能导致在抗疟药和沙利度胺治疗失败后,仅将柳氮磺胺吡啶用于重度耐药慢性红斑狼疮。然而,我们的研究表明,如其他作者所观察到的,慢乙酰化表型可预测免疫过敏事件,且可能是预测无反应的一个因素。如果这些结果得到其他研究的证实,对于快乙酰化者,有可能将柳氮磺胺吡啶推荐为盘状红斑狼疮的一种治疗方法。

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