Therapeutic Potential of Botulinum Toxin in Hailey–Hailey Disease

Background Hailey–Hailey disease (familial benign chronic pemphigus) is a rare autosomal dominant genodermatosis caused by ATP2C1 gene mutations, leading to defective calcium‐dependent ATPase. The function of this protein is to regulate calcium sequestration in the Golgi apparatus. While the mutation leads to impaired desmosome function, causing acantholysis of the suprabasal epidermis in the skin. Clinically, it presents with vesicles, erosions, fissures and weeping plaques, primarily in intertriginous areas. Symptoms worsen with heat, sweat, friction, and trauma, while treatment options remain limited. Objectives The aim of this systematic review was to review the available literature to assess the efficacy and safety of botulinum toxin as a therapeutic option for the treatment of Hailey–Hailey disease. Methods A literature review was conducted in Embase and MEDLINE using keywords like “Hailey–Hailey disease,” “pemphigus,” and “botulin toxin.” The search followed PRISMA guidelines, incorporating EMTREE and MESH terms. Inclusion criteria covered original trials, case reports, and case series in English until July 2025. Of 28 identified studies, 21 were included after further manual review. Results Twenty‐one articles involving 68 patients described the use of botulinum toxin in HHD. Most patients achieved significant improvement and partial or complete remission of skin symptoms after injection or reinjection of botulinum toxin. Only one patient showed no improvement in target lesions. Combined botulinum toxin, photodynamic therapy, and dapsone yielded superior improvement with PDT + BoNT‐A showing better outcomes than BoNT‐A alone. No side effects were observed. Conclusions Botulinum toxin appears to be a promising therapeutic alternative in HHD with a very good tolerability, both as a complementary treatment and as an adjuvant to other forms of therapy, such as PDT. Larger studies are required to confirm its efficacy, long‐term effects, and also to establish the optimal doses and number of botulinum toxin injections resulting in a standardized treatment regimen.