Treatment of Hailey-Hailey disease with biologics and small molecule inhibitors: a systematic review

Abstract Hailey-Hailey disease (HHD) is a rare genetic dermatosis characterized by recurrent flaccid vesicles and blisters on erythematous skin in friction areas. The disease follows a chronic relapsing course and has a significant psychological and social impact. Currently, there is no standardized therapeutic regimen for HHD, posing a challenge for dermatologists in managing the condition. We performed this systematic review to investigate the therapeutic role of biologics and small molecule inhibitors in the treatment of HHD. A systematic search was conducted of the PubMed, Embase, Web of Science, Scopus, and Cochrane databases from inception to January 1, 2024. A total of 31 HHD patients from 18 articles were included in the analysis. Biologics and small molecule inhibitors, including dupilumab, apremilast, upadacitinib, abrocitinib, adalimumab, and etanercept were evaluated. Most reported cases demonstrated clinical improvement after treatment initiation with few major adverse events. However, some patients experienced recurrences. In conclusion, biologics and small molecule inhibitors may offer a treatment alternative for refractory HHD patients, but further confirmation is necessary through large-scale randomized controlled clinical trials.