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硫唑嘌呤类过敏样反应——一例病例报告及文献综述

Azathioprine hypersensitivity-like reactions--a case report and a review of the literature.

作者信息

Knowles S R, Gupta A K, Shear N H, Sauder D

机构信息

Division of Dermatology, Sunnybrook Health Science Centre, Toronto, Canada.

出版信息

Clin Exp Dermatol. 1995 Jul;20(4):353-6. doi: 10.1111/j.1365-2230.1995.tb01343.x.

Abstract

Azathioprine is used in a variety of dermatological conditions. However, because of its side-effect profile, azathioprine is limited for use in patients with severe disease. An unpredictable, rare and potentially fatal side-effect of azathioprine is the development of a hypersensitivity reaction, often consisting of fever, hypotension and oliguria. We describe a 17-year-old patient with leucocytoclastic vasculitis who was placed on azathioprine; within 15 days of start of therapy, she developed a fever. Azathioprine was discontinued and an evaluation for sepsis was undertaken; all cultures were negative and the fever abated. Azathioprine was restarted 5 days later. After a single dose, fever, nausea and vomiting, diarrhoea, hypotension, tachycardia and oliguria developed and the patient was admitted to an intensive care unit. Azathioprine was discontinued and investigations revealed no sign of an infection. All the above signs and symptoms abated within 24 h and the patient was discharged from hospital in 7 days. A review of 28 case reports in the literature of azathioprine-induced hypersensitivity reactions suggest that most commonly a fever and gastrointestinal symptoms occurred on initial presentation. In addition, a maculopapular rash, urticaria, vasculitis, erythema multiforme or erythema nodosum may occur. Hepatotoxicity and nephritis have also been reported. The aetiology of the reaction is unknown but sudden onset of fever and hypotension suggests that this reaction may be due to cytokine or mediator release induced by azathioprine. As azathioprine is metabolized to 6-MP, rechallenges to both should be avoided in patients who experienced an azathioprine hypersensitivity-like reaction.

摘要

硫唑嘌呤用于多种皮肤病。然而,由于其副作用,硫唑嘌呤在重症患者中的使用受到限制。硫唑嘌呤一种不可预测、罕见且可能致命的副作用是发生过敏反应,通常表现为发热、低血压和少尿。我们描述了一名17岁患有白细胞破碎性血管炎的患者,她开始使用硫唑嘌呤;在治疗开始后的15天内,她出现了发热。停用硫唑嘌呤并对败血症进行评估;所有培养结果均为阴性,发热消退。5天后重新开始使用硫唑嘌呤。单次用药后,患者出现发热、恶心、呕吐、腹泻、低血压、心动过速和少尿,随后被收入重症监护病房。停用硫唑嘌呤,检查未发现感染迹象。上述所有症状在24小时内消退,患者在7天内出院。对文献中28例硫唑嘌呤引起的过敏反应病例报告的回顾表明,初次出现时最常见的是发热和胃肠道症状。此外,可能会出现斑丘疹、荨麻疹、血管炎、多形红斑或结节性红斑。也有肝毒性和肾炎的报道。该反应的病因尚不清楚,但发热和低血压的突然发作表明这种反应可能是由于硫唑嘌呤诱导的细胞因子或介质释放所致。由于硫唑嘌呤可代谢为6-巯基嘌呤,对于经历过硫唑嘌呤过敏样反应的患者,应避免再次使用这两种药物。

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