【摘要】 目的:探讨在携带HLA-B~*13:01基因的难治性皮肤病患者中，通过严密监测使用氨苯砜(DDS)治疗并早期识别、干预氨苯砜综合征(DHS)的可行性。方法:选取2例HLA-B~*13:01阳性、常规治疗无效的皮肤病患者(分别诊断为疱疹样皮炎和荨麻疹性血管炎)，在知情同意后予以DDS治疗，并进行每日体温监测。若出现发热(>37.5℃)，立即停药，进行血常规及肝肾功能检测，并给予甲泼尼龙治疗。同时采用酶联免疫斑点法(ELISpot)检测患者外周血中DDS特异性T细胞免疫反应。结果:2例患者分别在服药第22天和第38天出现发热伴肝功能异常，及时停药并接受糖皮质激素治疗后症状缓解，未进展为重症DHS。ELISpot检测显示两例患者外周血在DDS刺激后导致IFN-γ分泌增加，证实DDS为致敏药物。结论:对HLA-B~*13:01阳性且缺乏替代治疗方案的难治性皮肤病患者，在充分知情同意和严密监测下使用DDS，可实现原发病的有效治疗，并通过早期识别与干预避免DHS进展，为携带易感基因患者的个体化用药提供了临床参考。更多还原

【Abstract】 Objective: To explore the feasibility of utilizing dapsone( DDS) under intensive clinical monitoring for the treatment of refractory dermatoses in patients carrying the HLA-B~*13: 01 allele,with a focus on the early identification and intervention of dapsone hypersensitivity syndrome( DHS). Methods: Two patients with HLA-B~*13: 01 and refractory skin diseases( diagnosed with dermatitis herpetiformis and urticarial vasculitis,respectively) were selected. After providing informed consent,they were administered DDS and subjected to daily body temperature monitoring. Upon occurrence of fever( >37.5℃),DDS was discontinued immediately. Complete blood count and liver/kidney function tests were performed,followed by methylprednisolone treatment. Concurrently,the enzyme-linked immunospot( ELISpot) assay was employed to detect DDS-specific T-cell immune responses in peripheral blood. Results: The two patients developed fever accompanied by liver function abnormalities on day 22 and day 38 of medication,respectively. Prompt discontinuation of DDS and initiation of glucocorticoid therapy led to symptom resolution without progression to severe DHS. ELISpot assays demonstrated increased DDS-specific IFN-γ secretion in both patients,confirming DDS as the causative drug. The primary diseases were controlled post-treatment,with no severe adverse reactions observed. Conclusion: For HLA-B~*13: 01-positive patients with refractory dermatoses lacking alternative treatment options,the use of DDS with thorough informed consent and stringent monitoring can achieve effective management of the primary disease. Early recognition and intervention can prevent the progression of DHS,providing a clinical reference for the personalized use of this medication in patients carrying susceptible alleles.更多还原