Treatment Algorithm Suggestion for Hailey-Hailey Disease

Abstract

Hailey-Hailey disease is a rare genodermatosis, with an autosomal dominant inheritance pattern. Its incidence is estimated at 1/50,000. It is characterized by compromised adhesion between epidermal keratinocytes. It results from a heterozygous mutation in the ATP2C1 gene, causing the diagnostic triad: suprabasal acantholysis, loosely joined keratinocytes, and occasional dyskeratosis. Clinically, it presents between the third and fourth decades as blisters and flaccid vesicles, leading to the development of fissures, erosions, rhagades, and vegetations. Lesions are distributed symmetrically in flexural areas. It has a chronic relapsing course with periods of remission and exacerbation. There is no cure and therapeutic options remain limited. General non-pharmacological measures are crucial. Treatments include topical agents (corticosteroids, calcineurin inhibitors, antibiotics, calcitriol) and systemic agents (antibiotics, anticholinergics, retinoids, apremilast, dapsone, immunosuppressants, biologicals, naltrexone, vitamin D), as well as procedural therapy such as carbon dioxide laser, botulinum toxin, dermabrasion, photodynamic therapy, and surgery. Given the lack of evidence-based guidelines and large clinical trials, evaluating the effectiveness and safety of treatments is challenging. This review presents a systematic analysis of the literature with a focus on both established and emerging treatment options for Hailey-Hailey disease with the aim to provide a therapeutic algorithm. The evidence supporting each treatment option will be assessed, emphasizing the strength of the data to guide clinical decision-making.