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与用于治疗银屑病的富马酸酯相关的药物性范科尼综合征:病例系列

Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: a case series.

作者信息

Balak Deepak M W, Bouwes Bavinck Jan Nico, de Vries Aiko P J, Hartman Jenny, Neumann Hendrik A Martino, Zietse Robert, Thio Hok Bing

机构信息

Department of Dermatology , Erasmus Medical Center , Rotterdam , The Netherlands.

Department of Dermatology , Leiden University Medical Center , Leiden , The Netherlands.

出版信息

Clin Kidney J. 2016 Feb;9(1):82-9. doi: 10.1093/ckj/sfv114. Epub 2015 Nov 10.

Abstract

BACKGROUND

Fumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced Fanconi syndrome.

METHODS

Descriptive case series with two cases of Fanconi syndrome associated with FAE treatment diagnosed at two Dutch university nephrology departments, three cases reported at the Dutch and German national pharmacovigilance databases and six previously reported cases.

RESULTS

All 11 cases involved female patients with psoriasis. The median age at the time of onset was 38 years [interquartile range (IQR) 37-46]. Patients received long-term FAEs treatment with a median treatment duration of 60 months (IQR 28-111). Laboratory tests were typically significant for low serum levels of phosphate and uric acid, while urinalysis showed glycosuria and proteinuria. Eight (73%) patients had developed a hypophosphataemic osteomalacia and three (27%) had pathological bone fractures. All patients discontinued FAEs, while four (36%) patients were treated with supplementation of phosphate and/or vitamin D. Five (45%) patients had persisting symptoms despite FAEs discontinuation.

CONCLUSIONS

FAEs treatment can cause drug-induced Fanconi syndrome, but the association has been reported infrequently. Female patients with psoriasis treated long term with FAEs seem to be particularly at risk. Physicians treating patients with FAEs should be vigilant and monitor for the potential occurrence of Fanconi syndrome. Measurement of the urinary albumin:total protein ratio is a suggested screening tool for tubular proteinuria in Fanconi syndrome.

摘要

背景

富马酸酯(FAEs)是一种用于治疗银屑病和多发性硬化症的口服免疫调节药物,据传闻,它会因药物性范科尼综合征导致近端肾小管功能障碍。关于FAE诱导的范科尼综合征的临床结局,可用数据很少。

方法

描述性病例系列,包括在荷兰两个大学肾脏病科诊断的2例与FAE治疗相关的范科尼综合征病例、荷兰和德国国家药物警戒数据库报告的3例以及先前报告的6例。

结果

所有11例均为患有银屑病的女性患者。发病时的中位年龄为38岁[四分位间距(IQR)37 - 46]。患者接受长期FAEs治疗,中位治疗持续时间为60个月(IQR 28 - 111)。实验室检查通常显示血清磷酸盐和尿酸水平低具有显著意义,而尿液分析显示糖尿和蛋白尿。8例(73%)患者出现了低磷性骨软化症,3例(27%)发生了病理性骨折。所有患者均停用了FAEs,而4例(36%)患者接受了磷酸盐和/或维生素D补充治疗。5例(45%)患者在停用FAEs后仍有持续症状。

结论

FAEs治疗可导致药物性范科尼综合征,但这种关联报道较少。长期接受FAEs治疗的银屑病女性患者似乎尤其危险。治疗FAEs患者的医生应保持警惕,监测范科尼综合征的潜在发生情况。尿白蛋白:总蛋白比值的测定是范科尼综合征中肾小管蛋白尿的建议筛查工具。

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