Reduced induction of human β‐defensins is involved in the pathological mechanism of cutaneous adverse effects caused by epidermal growth factor receptor monoclonal antibodies

Abstract

Summary Epidermal growth factor receptor inhibitors (EGFRIs) frequently cause cutaneous adverse effects such as papulopustular eruptions. However, the mechanism of the reactions remains unclear. To assess the pathological mechanism of cutaneous adverse reactions caused by EGFRIs, we investigated whether EGFRIs have an influence on the innate immune response of the skin. Levels of human β‐defensins (hBDs), which serve as the first line of defence against infection by pathogenic microorganisms, in the stratum corneum samples of patients treated with EGFR. monoclonal antibodies were measured before and after starting therapy. There were no obvious trends in hBD production in patients without eruptions, whereas a significant decrease in hBD1 and hBD3 production and a nonsignficant decrease in hBD2 production were observed in patients who developed papulopustular eruptions. Our results suggest that a reduction in hBD contributes to the increased incidence of papulopustular eruptions.

Persistent alteration of the skin microbiome in patients with skin rash after receiving EGFR inhibitor treatment

“…A potential mechanism underlying persistent dysbiosis is disturbed keratinocyte differentiation caused by EGFRIs, which may impair skin homeostasis. EGFR blockade reduces the expression of filaggrin, tight junctions, and antibacterial peptides 2,7,8 . As filaggrin plays a role in skin barrier function by maintaining the acidity and hydration of the stratum corneum, 9 the decreased expression will cause major disruption to skin homeostasis; Impaired tight junction induces the penetration of external virulence and moisture leakage of internal skin 10 ; and decrease of antibacterial peptides, such as human β‐defensins and cathelicidin, promotes to the invasion and colonization of various microbe including pathogens 11 .…”

Skin microbiome in cancer patients with pruritus and other skin toxic reactions related to anticancer therapy: A review

“…Так, R. Ommori и соавт. показали снижение содержания бета-дефензинов 1, 2 и 3-го типа у пациентов с акнеформной сыпью на фоне терапии ингибиторами EGFR [19]. У пациентов без акнеформных высыпаний начало терапии не сопровождалось снижением содержания дефензинов в роговом слое, что может свидетельствовать о потенциально существенной роли лекарственно индуцированного изменения микробиоты в развитии кожных токсических реакций на фоне противоопухолевой терапии.…”