Evaluation of Prospective HLA-B*13:01 Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy
Evaluation of Prospective HLA-B*13:01 Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy
复制标题
前瞻性 HLA-B13:01 筛查预防麻风患者氨苯砜超敏综合征的评估
DOI：
10.1001/jamadermatol.2018.5360
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发表时间：
2019-06-01
期刊：
影响因子：
10.9
通讯作者：
Liu, Qiao
中科院分区：
文献类型：
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作者：
Liu, Hong;Wang, Zhenzhen;Liu, Qiao
氨苯砜超敏综合征（DHS）是与氨苯砜给药相关的最严重的不良反应，也是麻风患者死亡的主要原因之一，其标准治疗包括氨苯砜、利福平和氯法齐明的多药治疗（MDT）。尽管HLA-B*13：01多态性已被确定为中国人群DHS的遗传决定因素，但迄今为止尚未进行任何研究来评估前瞻性HLA-B*13：01筛查是否可以通过识别不应接受氨苯砜的患者来预防DHS。目的评价前瞻性HLA-B*13：01筛查对HLA-B*13：01阳性麻风患者排除氨苯砜治疗以降低DHS发病率的临床应用价值。设计、设置和样本一项前瞻性队列研究于2015年2月15日至2018年4月30日在中国21个省份进行。共有1539例新诊断的麻风患者入组，既往未接受过氨苯砜治疗。在排除了对砜类过敏或葡萄糖-6-磷酸脱氢酶缺乏的患者后，1512例患者接受了HLA-B*13：01基因分型。所有患者在治疗后的前8周内每周随访一次，以监测不良事件。HLA-B*13：01携带者被告知从治疗方案中排除氨苯砜，非携带者接受标准MDT。主要结局和指标主要结局是DHS的发生率。DHS的历史发生率（1.0%）用作对照。结果在1512例患者中（1026例[67.9%]男性，486例[32.1%]女性;平均[SD]年龄43.1 [16.2]岁），261例（17.3%）被确定为HLA-B*13：01等位基因携带者。在随访期间，共观察到384例患者的714起不良事件。在接受氨苯砜治疗的1251例HLA-B*13：01阴性患者中，没有一例发生氨苯砜超敏综合征，而根据每年1.0%的历史发病率，预计约有13例患者发生DHS（P=2.05x10（-5））。其他不良事件（包括皮肤病或其他事件）与HLA-B*13：01状态之间无显著相关性。结论前瞻性筛查HLA-B*13：01阳性的麻风患者，并在MDT中停用氨苯砜，可显著降低DHS的发生率。
ImportanceDapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone. ObjectiveTo evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01-positive leprosy. Design, Setting, and ParticipantsA prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events. ExposuresPatients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT. Main Outcomes and MeasuresThe primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control. ResultsAmong 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01-negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P=2.05x10(-5)). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status. Conclusions and RelevanceProspective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.