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氨甲环酸诱导的中毒性表皮坏死松解症。

Tranexamic acid-induced toxic epidermal necrolysis.

机构信息

Department of Dermatology, School of Medicine, University Clinic of Navarra, Pamplona, Spain.

出版信息

Ann Pharmacother. 2013 Mar;47(3):e16. doi: 10.1345/aph.1R637. Epub 2013 Feb 27.

Abstract

OBJECTIVE

To report a case of toxic epidermal necrolysis (TEN) induced by orally administered tranexamic acid in a patient with liver cirrhosis and acute rectal bleeding.

CASE SUMMARY

A 67-year-old male with a history of liver cirrhosis due to alcohol consumption with ascitic decompensation, esophageal varices, and multifactorial renal insufficiency presented with rectal bleeding. The patient was prescribed oral tranexamic acid (1000 mg every 8 hours), with partial resolution of symptoms. Ten days after treatment with tranexamic acid began, a purplish macular rash appeared over the patient's trunk. The dose of tranexamic acid was reduced to 1000 mg every 12 hours, adjusting for renal function. In the following days the lesions extended and became confluent with blisters and epidermal necrosis. Multiple mucosal surfaces were also affected. He denied allergies to any medications and had no history of tranexamic acid exposure. Treatment with tranexamic acid was suspended and fluid replacement therapy, oral prednisone therapy (0.4 mg/kg per day), and N-acetylcysteine 2 g every 6 hours was started, with the empiric diagnosis of TEN. Results of a skin biopsy were compatible with TEN. Resolution of the skin lesions was favorable, but after 2 weeks the patient died secondary to acute renal failure, respiratory infection, and multiorgan failure.

DISCUSSION

TEN is a rare, severe mucocutaneous adverse reaction. Although infrequent, TEN has a significant impact on public health because of its high mortality. Its pathogenesis is unclear, but it seems to be a form of delayed hypersensitivity. To our knowledge, a well-documented case of TEN following tranexamic acid use has not been reported (MEDLINE search to June 2012). There have been recent reports of skin hypersensitivity reactions through different mechanisms (immunologic and nonimmunologic). The Naranjo probability scale indicates a probable relationship between the development of TEN and tranexamic acid use in our patient.

CONCLUSIONS

This appears to be the first report of a case of TEN that occurred in a patient being treated with oral tranexamic acid. Clinicians should be made aware of this potential severe cutaneous adverse reaction that may be caused by tranexamic acid administration.

摘要

目的

报告 1 例肝硬化合并急性直肠出血患者口服氨甲环酸引起中毒性表皮坏死松解症(TEN)。

病例总结

1 例 67 岁男性,因饮酒导致肝硬化合并腹水、食管静脉曲张和多因素肾功能不全,出现直肠出血。给予患者口服氨甲环酸(每 8 小时 1000mg)治疗,症状部分缓解。氨甲环酸治疗 10 天后,患者躯干出现紫色斑片状皮疹。根据肾功能调整氨甲环酸剂量为每 12 小时 1000mg。随后,皮损扩展并融合成水疱和表皮坏死。多个黏膜表面也受到影响。他否认对任何药物过敏,也没有氨甲环酸暴露史。停用氨甲环酸,给予补液、口服泼尼松(0.4mg/kg/天)和每 6 小时给予 N-乙酰半胱氨酸 2g 治疗,经验性诊断为 TEN。皮肤活检结果符合 TEN。皮肤病变消退良好,但 2 周后患者因急性肾衰竭、呼吸道感染和多器官功能衰竭死亡。

讨论

TEN 是一种罕见的严重黏膜皮肤不良反应。尽管不常见,但 TEN 对公共卫生的影响很大,因为它的死亡率很高。其发病机制尚不清楚,但似乎是一种迟发型超敏反应。据我们所知,(截至 2012 年 6 月 MEDLINE 检索)尚未有报道称使用氨甲环酸后出现 TEN 的明确病例。最近有报道称,通过不同机制(免疫和非免疫)发生皮肤过敏反应。Naranjo 概率量表表明,在我们的患者中,TEN 的发生与氨甲环酸的使用之间存在可能的关系。

结论

这似乎是首例报告的口服氨甲环酸治疗患者发生 TEN 的病例。临床医生应意识到氨甲环酸可能引起这种潜在的严重皮肤不良反应。

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