Inherited Acantholytic Disorders

Abstract

Darier disease (DD) and Hailey–Hailey disease (HHD) are autosomal dominant disorders characterised by epidermal acantholysis. They have a similar molecular pathogenesis, with mutations in 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 characterised by loss of epidermal intercellular adhesion (acantholysis). DD may be accompanied by neuropsychiatric symptoms such as depression, epilepsy, learning disabilities or bipolar disease. 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.