Apocytolysis, a proposed mechanism of blister formation in epidermolysis bullosa simplex

Epidermolysis bullosa simplex (EBS) is caused by keratin 5 and 14 mutations. In vitro studies revealed that susceptibility to caspase 8-mediated apoptosis is increased in keratin 14 mutated keratinocytes. We aimed to investigate the role of apoptotic/inflammatory pathways in the pathogenesis of EBS by studying the expression of caspase 8 in lesional and non-lesional skin compared to controls. Ten EBS patients proved by electron microscopy and five age and sex matched healthy volunteers were the subjects of this case control study. Caspase 8 expression was studied by immunohistochemistry. Caspase 8 expression in lesional and non-lesional skin was significantly higher than in controls (p < 0.01 and p = 0.013, respectively) with no significant difference between lesional and non-lesional skin. Lesional skin had significantly higher density of dermal infiltrate (p = 0.02). Caspase 8 expression in lesional skin was significantly correlated with the extent of the disease, rate of blistering, and density of dermal infiltrate (r = 0.835; p = 0.003, r = 0.889; p = 0.001 and r = 0.776; p = 0.008 respectively). Caspase 8-mediated apoptosis is an integral component of an orchestra of events conducted by keratin mutation. Apo-cytolysis is proposed to better describe the mechanism of blistering in EBS. The small number of cases is a limitation.