Skin microbial dysbiosis is a characteristic of systemic drug-related intertriginous and flexural exanthema-like lesions induced by EGFR inhibitor

Objectives: To investigate the characteristics of the skin microbiome in severe afatinib-induced skin toxicity.Methods: Body site-matched skin surface samples were collected from the lesions on seven flexural sites of one lung cancer (Patient 1) with serious systemic drug-related intertriginous and flexural exanthema (SDRIFE)-like toxicity induced by EGFR-TKI and three healthy age/sex matched controls for whole metagenomics sequencing analysis. Lung cancer Patient 1 and Patient 2 were prescribed minocycline and followed up.Results: In SDRIFE-like toxicities induced by afatinib, lesion microbiota richness (ACE and Chao1 index: p < 0.001) and diversity (Shannon's and Simpson's diversity indices: p < 0.01) were reduced. Similarly, the beta diversity analysis (R = 1, p = 0.002 for ANOSIM) showed that the apparent difference in the microbiota composition was statistically significant. The microbial taxa composition in the patient showed an increased abundance of pathogenic bacteria and a decreased abundance of commensal bacteria. LEfSe analysis identified strong bacterial pathogenicity in the patient, while healthy controls exhibited enrichment in several pathways that are beneficial for skin commensal bacteria and skin physiology, including key amino acid metabolism, energy/lipid/glycan biosynthesis/metabolism, and cofactors/vitamins biosynthesis. Ultimately, the patients experienced significant improvement with minocycline.Conclusion: Microbial dysbiosis is a characteristic of severe SDRIFE-like toxicity induced by afatinib.