Inherited Acantholytic Disorders

Inherited acantholytic disorders represent a heterogeneous group of genodermatoses characterized by impaired keratinocyte adhesion, resulting in intraepidermal clefting and blister formation. These disorders, which include Darier disease, Hailey–Hailey disease, are primarily linked to mutations affecting desmosomal proteins, calcium pumps, or keratinocyte structural integrity. Clinical manifestations range from localized fragile vesicles and erosions to widespread keratotic papules and recurrent painful erosions, often exacerbated by heat, sweating, or mechanical trauma. Advances in molecular genetics have unraveled the pathogenic mechanisms, particularly the role of altered calcium homeostasis and defective desmosome assembly, offering valuable diagnostic insights. Current management remains symptomatic, focusing on reducing triggers, topical and systemic retinoids, and emerging targeted therapies.