Targeted therapy guided by single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: A case report

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS) is a potentially fatal multi-organ inflammatory disease associated with herpesvirus reactivation and subsequent onset of autoimmune diseases(1–4). Pathophysiology remains elusive and therapeutic options are limited. Cases refractory to corticosteroid therapy pose a clinical challenge(1,5), and approximately 30% of DiHS/DRESS patients develop complications including infections and inflammatory/autoimmune diseases(1,2,5). Progress in single-cell RNA sequencing (scRNAseq) provides an opportunity to dissect human disease pathophysiology at unprecedented resolutions(6), particularly in diseases lacking animal models, such as DiHS/DRESS. We performed scRNAseq on skin and blood from a refractory DiHS/DRESS case, found JAK-STAT signaling pathway as potentially targetable, and further identified that central memory CD4(+) T cells were enriched with HHV6b DNA. Intervention via tofacitinib enabled disease control and tapering of other immunosuppressive agents. Furthermore, tofacitinib, as well as anti-viral agents, suppressed culprit-induced T cell proliferation in vitro, identifying the JAK-STAT pathway and herpesviruses as potential therapeutic targets in DiHS/DRESS. Thus, scRNAseq analyses guided therapeutic decisions that enabled successful therapeutic intervention in this refractory DiHS/DRESS case. Employing scRNAseq analyses in human diseases may facilitate our understanding of complicated disease pathophysiology and further provide an alternative approach in personalized medicine.