Fixed Drug Eruptions (FDE) are an intriguing disease as lesions uniquely reappear at the same anatomic site upon re-exposure to a culprit drug. Disease pathogenesis is poorly understood. To illuminate the immunobiology of FDE, we performed high-throughput TCR sequencing, transcriptional profiling and tissue staining with microscopy of skin specimens from FDE patients and healthy controls. TCR sequencing revealed immunodominant clones, either monoclonal or oligoclonal pattern, in lesional skin that were absent in control skin taken from the same patient. Transcriptional profiling suggested that central memory type or peripheral type T cells recruited into skin were potentially key protagonists in FDE. Data favored Th1 polarization of T cells, with CXCL9, CXCL10, CXCL11 and STAT1 significantly up-regulated and GATA3 down-regulated, and cytotoxic CD8+ T cells producing TNFα and cytotoxic granules containing perforin and granzymes. Comparatively, granulysin and Fas/FasL were not differentially expressed. NK cell receptor activation pathway was upregulated, suggesting a potential alternative or addition to standard MHC:TCR signaling. Moreover, the JAK3/STAT1 pathway was upregulated, identifying a possible alternative approach to steroids for targeted treatment. Findings suggested previously unappreciated roles for NK cells and several antigen presenting cell subsets in disease. Immunohistochemical and immunofluorescence analysis confirmed a heavy T cell infiltrate of both CD4 and CD8 T cell subsets, that were  not  type, but also supported a significant non-T cell infiltrate. This study illuminates the immunologic complexity of FDE and provides a strong platform for future immunologic studies.

ESDRLB008 - Insights on the immunologic complexity of Fixed Drug Eruptions

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING