915 Acneiform eruptions caused by EGFR inhibitors may result from reduced expression of human β-defensin-3 induced by S. epidermidis

EGFR inhibitors (EGFRIs) frequently cause cutaneous adverse events such as acneiform rashes. However, the pathogenetic mechanism of remains unclear. We previously reported that EGFRIs suppressed expression human β-defensin-3 (hBD3) in patients treated with and cultured keratinocytes induced by S. epidermidis via Toll-like receptor 2 (TLR2). Because staphylococci are commonly detected skin lesions, we hypothesized commensal maintain innate immune response inducing hBD3 EGF-signaling pathway. To clarify pathogenesis EGFRI-induced eruptions, analyzed whether exposed to produce EGF. First, determine ligands induce hBD3, were administered into keratinocyte culture medium. The well epidermidis. Furthermore, markedly increased TGF-α. and/or TGF-α administrated medium presence or absence EGFRI verify suppressive effects on was stimulated increase completely inhibited EGFRI. Next, is TLR2, TLR2-knockdown epidermidis,and levels measured. significantly keratinocytes. In addition, also inhibition TLR2. Our results suggest under normal condition, but EGFRIs, decreased, resulting eruptions.