title: Apocytolysis, a proposed mechanism of blister formation in epidermolysis bullosa simplex.
abstract: 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.
authors.affiliation: Dermatology Department (Dermatopathology Unit), Faculty of Medicine, Cairo University, Kasr Al Aini Street, Cairo, 11562, Egypt.
authors.forename: Marwa S
authors.initials: MS
authors.lastname: El-Hawary
authors.forename: Mona R E
authors.initials: MR
authors.lastname: Abdel-Halim
authors.forename: Safinaz S
authors.initials: SS
authors.lastname: Sayed
authors.forename: Heba A
authors.initials: HA
authors.lastname: Abdelkader
mesh_terms: D000293:Adolescent; D017209:Apoptosis; D001768:Blister / Q000503:physiopathology*; D016022:Case-Control Studies; D053181:Caspase 8 / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016110:Epidermolysis Bullosa Simplex / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D007633:Keratins / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000502:physiology
chemical_list: D007633:Keratins; D053181:Caspase 8