Erythroderma and Epidermal Necrosis Induced by a Type of Proton Pump Inhibitor in Beagle Dogs

Abstract

Reddish skin covering the entire body (erythroderma) was observed in a preliminary one-week oral toxicity study of a type of proton pump inhibitor in Beagle dogs. Histologically, full-thickness epidermal necrosis accompanied by apoptosis, evidenced by an immunohistochemical positive reaction to cleaved caspase-3, and detachment of the epidermis were observed in the skin. In the epidermis and upper dermis, a slight infiltration of mononuclear cells was seen, which was predominantly positive for MAC387 (macrophages) and partly positive for CD3 (T lymphocytes). These findings have some similarities to drug-induced severe skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and may represent incipient changes of such lesions. The skin lesions observed in these dogs are being considered as a potential animal model of cutaneous drug reactions.