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HLA-B58 有助于临床决策是否在慢性肾功能不全患者中开始使用别嘌醇。

HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency.

机构信息

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Nephrol Dial Transplant. 2011 Nov;26(11):3567-72. doi: 10.1093/ndt/gfr060. Epub 2011 Mar 10.

Abstract

BACKGROUND

Although allopurinol is a very effective urate-lowering drug for complicated hyperuricemia, in some patients, it can induce severe cutaneous adverse reactions (SCARs). Recent investigations suggest that HLA-B5801 is a very strong marker for allopurinol-induced SCARs, especially in the population with a high frequency of HLA-B5801. Korea is one of the countries with a high frequency of HLA-B*5801 which is the only subtype of HLA-B58 in the Korean population. Objective. This study was conducted to find out the incidence of allopurinol-induced hypersensitivity on patients with chronic renal insufficiency (CRI) according to HLA-B58 and the clinical implications of HLA-B58 as a risk marker for the development of allopurinol-induced hypersensitivity.

METHODS

We retrospectively reviewed the medical records of patients with CRI who took allopurinol and carried out serologic human leukocyte antigen (HLA) typing for kidney transplantation between January 2003 and May 2010.

RESULTS

Among a total of 448 patients with CRI, 16 (3.6%) patients experienced allopurinol hypersensitivity. Nine of these patients (2.0%) were diagnosed with SCARs (two Stevens-Johnson syndrome and seven allopurinol hypersensitivity syndrome) and seven patients (1.6%) had simple maculopapular rashes. The HLA-B58 allele was present in all patients with allopurinol-induced SCARs, while the frequency of HLA-B58 was only 9.5% in allopurinol-tolerant patients (P < 0.05). The incidence of allopurinol-induced SCARs in CRI shows a wide disparity according to HLA-B58 [18% in HLA-B58 (+) versus 0% in HLA-B58 (-)]. Among patients without HLA-B58, most (98.2%) of the CRI patients were tolerant to allopurinol and only 1.8% experienced simple rashes after taking allopurinol.

CONCLUSIONS

In this study, the incidence of allopurinol-induced SCARs was considerably high in CRI patients with HLA-B58. This finding indicates that the presence of HLA-B58 may increase the risk of allopurinol-induced SCARs. Screening tests for HLA-B58 in CRI patients will be clinically helpful in preventing severe allopurinol hypersensitivity reactions.

摘要

背景

尽管别嘌醇是治疗复杂性高尿酸血症的非常有效的尿酸降低药物,但在某些患者中,它会引起严重的皮肤不良反应(SCARs)。最近的研究表明,HLA-B5801 是别嘌醇诱导的 SCARs 的一个非常强的标志物,尤其是在 HLA-B5801 频率较高的人群中。韩国是 HLA-B5801 频率较高的国家之一,HLA-B5801 是韩国人群中唯一的 HLA-B58 亚型。目的:本研究旨在探讨 HLA-B58 与慢性肾功能不全(CRI)患者接受别嘌醇治疗后发生过敏反应的相关性,以及 HLA-B58 作为别嘌醇诱导过敏反应发生风险标志物的临床意义。

方法

我们回顾性分析了 2003 年 1 月至 2010 年 5 月间接受肾移植的 CRI 患者的病历,这些患者均接受别嘌醇治疗,并进行了血清人类白细胞抗原(HLA)分型。

结果

在总共 448 名 CRI 患者中,有 16 名(3.6%)患者出现别嘌醇过敏反应。其中 9 名患者(2.0%)被诊断为 SCARs(2 例史蒂文斯-约翰逊综合征和 7 例别嘌醇过敏综合征),7 名患者(1.6%)出现单纯性斑丘疹。所有别嘌醇诱导的 SCARs 患者均携带 HLA-B58 等位基因,而在别嘌醇耐受患者中 HLA-B58 的频率仅为 9.5%(P<0.05)。根据 HLA-B58,CRI 患者中别嘌醇诱导的 SCARs 的发生率差异很大[HLA-B58(+)为 18%,HLA-B58(-)为 0%]。在没有 HLA-B58 的患者中,大多数(98.2%)CRI 患者对别嘌醇耐受,仅有 1.8%的患者在服用别嘌醇后出现单纯皮疹。

结论

在这项研究中,HLA-B58 阳性的 CRI 患者中别嘌醇诱导的 SCARs 发生率相当高。这一发现表明 HLA-B58 的存在可能增加别嘌醇诱导的 SCARs 的风险。在 CRI 患者中进行 HLA-B58 筛查试验将有助于临床预防严重的别嘌醇过敏反应。

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