Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin
Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin
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DOI：
10.1136/annrheumdis-2014-205577
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发表时间：
2015-12-01
影响因子：
27.4
通讯作者：
Hung, Shuen-Iu
中科院分区：
文献类型：
--
作者：
Chung, Wen-Hung;Chang, Wan-Chun;Hung, Shuen-Iu
目的别嘌呤醇（Allopurinol）是一种抗高尿酸血症药物，是引起严重皮肤不良反应（SCAR）的常见原因之一，包括嗜酸性粒细胞增多性药疹（DRESS）、Stevens-Johnson综合征（SJS）和中毒性表皮坏死（TEN）。别嘌呤醇相关性SCAR的预后因素尚不清楚。本研究旨在探讨剂量，肾功能，血浆水平的oxypurinol和颗粒溶素（一种细胞毒性蛋白的SJS/TEN），疾病的严重程度和死亡率在别嘌呤醇-SCAR.Methods我们前瞻性地纳入48例别嘌呤醇-SCAR患者（26 SJS/TEN和22 DRESS）和138别嘌呤醇耐受对照组从2007年至2012年。结果别嘌呤醇-SCAR与HLA-B*58：01基因型密切相关（P < 0.05），与HLA-B *58：01基因型密切相关（P < 0.05），与HLA-B *58：01基因型密切相关（P < 0.05）。
Objective Allopurinol, an antihyperuricaemic agent, is one of the common causes of life-threatening severe cutaneous adverse reactions (SCAR), including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The prognostic factors for allopurinol-related SCAR remain unclear. This study aimed to investigate the relationship of dosing, renal function, plasma levels of oxypurinol and granulysin (a cytotoxic protein of SJS/TEN), the disease severity and mortality in allopurinol-SCAR.Methods We prospectively enrolled 48 patients with allopurinol-SCAR (26 SJS/TEN and 22 DRESS) and 138 allopurinol-tolerant controls from 2007 to 2012. The human leucocyte antigen (HLA)-B*58:01 status, plasma concentrations of oxypurinol and granulysin were determined.Results In this cohort, HLA-B*58:01 was strongly associated with allopurinol-SCAR (p