Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS) is a potentially fatal multiorgan inflammatory disease associated with herpesvirus reactivation and subsequent onset of autoimmune diseases^1,2,3,4. Pathophysiology remains elusive and therapeutic options are limited. Cases refractory to corticosteroid therapy pose a clinical challenge^1,5 and approximately 30% of patients with DiHS/DRESS develop complications, including infections and inflammatory and autoimmune diseases^1,2,5. Progress in single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect human disease pathophysiology at unprecedented resolutions⁶, particularly in diseases lacking animal models, such as DiHS/DRESS. We performed scRNA-seq on skin and blood from a patient with refractory DiHS/DRESS, identifying the JAK–STAT signaling pathway as a potential target. We further showed that central memory CD4⁺ T cells were enriched with DNA from human herpesvirus 6b. Intervention via tofacitinib enabled disease control and tapering of other immunosuppressive agents. Tofacitinib, as well as antiviral agents, suppressed culprit-induced T cell proliferation in vitro, further supporting the roles of the JAK–STAT pathway and herpesviruses in mediating the adverse drug reaction. Thus, scRNA-seq analyses guided successful therapeutic intervention in the patient with refractory DiHS/DRESS. scRNA-seq may improve our understanding of complicated human disease pathophysiology and provide an alternative approach in personalized medicine.

药物引起的超敏反应综合征/嗜酸性粒细胞增多和全身症状的药物反应 (DiHS/DRESS) 是一种潜在致命的多器官炎症性疾病，与疱疹病毒再激活和随后发生的自身免疫性疾病^1,2,3,4相关。病理生理学仍然难以捉摸，治疗选择有限。对皮质类固醇治疗无效的病例构成临床挑战^1,5，大约 30% 的 DiHS/DRESS 患者出现并发症，包括感染和炎症和自身免疫性疾病^1,2,5。单细胞 RNA 测序 (scRNA-seq) 的进展为以前所未有的分辨率剖析人类疾病的病理生理学提供了机会⁶，尤其是在缺乏动物模型的疾病中，例如 DiHS/DRESS。我们对难治性 DiHS/DRESS 患者的皮肤和血液进行了 scRNA-seq，将 JAK-STAT 信号通路确定为潜在目标。我们进一步表明中央记忆 CD4 ⁺T 细胞富含来自人类疱疹病毒 6b 的 DNA。通过托法替尼进行干预可以控制疾病并逐渐减少其他免疫抑制剂。托法替尼以及抗病毒药物在体外抑制了罪魁祸首诱导的 T 细胞增殖，进一步支持了 JAK-STAT 通路和疱疹病毒在介导药物不良反应中的作用。因此，scRNA-seq 分析指导了对难治性 DiHS/DRESS 患者的成功治疗干预。scRNA-seq 可以提高我们对复杂人类疾病病理生理学的理解，并为个性化医疗提供一种替代方法。