Involvement of the adherens junction – actin filament system in acantholytic dyskeratosis of Hailey‐Hailey disease

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Abstract
Hailey‐Hailey disease is a blistering genodermatosis that shows acantholytic dyskeratosis throughout the epidermis. The aim of our study was to investigate the involvement of adherens structures and cytofilaments in this particular type of acantholysis. Both lesional and non‐lesional skin from 18 patients was studied histologically and ultrastructurally. Additionally, the samples were stained for desmosomes, adherens junctions, keratin filaments, actin filaments, and actin‐associated proteins, and finally investigated with an electron and a confocal laser scanning microscope (CLSM), respectively. Acantholytic dyskeratosis was not only confined to lesions, but was also focally detectable in clinically unaffected skin. Despite disruption and internalization of the desmosomes, keratinocytes remained linked together by well‐preserved adherens junctions. Staining for actin filaments with fluorochrome‐labeled phalloidin showed a remarkable formation of actin stress fibers in these keratinocytes. Thus, incomplete acantholysis, as demonstrable in both lesional and non‐lesional skin of Hailey‐Hailey patients, may be due to a cohesive function of the adherens junction‐actin system succeeding the dissolution of desmosomes. Most remarkably, none of the adnexal epithelia expressed the intrinsic defect of cell adhesion. This finding offers an explanation for the successful treatment of Hailey‐Hailey disease by dermabrasion, which after complete removal of the involved epidermis results in reepithelialization from skin appendages.