Inherited Acantholytic Disorders

Abstract

Darier disease (DD) and Hailey–Hailey disease (HHD) are autosomal dominant disorders characterized by epidermal acantholysis. They have a similar molecular pathogenesis, with mutations in the intracellular calcium pumps of the endoplasmic reticulum (SERCA2) and Golgi (SPCA1), respectively. DD presents with persistent, hyperkeratotic papules in a seborrhoeic distribution, associated with nail changes and palmar pitting. HHD presents with painful, mainly flexural, erosions. In both, secondary infection is common and hypertrophic flexural disease can be disabling. Histologically, both are characterized by loss of epidermal intercellular adhesion (acantholysis). In DD, acantholysis is predominantly suprabasal and there is overlying dyskeratosis. In HHD, acantholysis is more diffuse. First line topical treatment is with emollients, antimicrobials and corticosteroids. Oral antibiotics are often necessary for exacerbations; other systemic options include retinoids and ciclosporin. Physical measures such as laser resurfacing, photodynamic therapy, botulinum toxin and surgical interventions can be considered in refractory cases.

Carcinoma in situ Arising in a Case of Hailey-Hailey Disease

“…It was first described by the Hailey brothers in 1939. [ 1 ] Intraepidermal neoplasms are conditions which result from dysplasia of the intraepithelial portion of skin or mucosal surface. [ 2 ] The predisposing factors for the development of intraepidermal neoplasia include arsenic consumption, ionizing radiation, skin injury following chronic inflammation such as lupus vulgaris and lupus erythematosus.…”