Abstract
Hailey-Hailey disease (HHD) is a rare autosomal dominant blistering disorder caused by mutations in the ATP2C1 gene, which impair keratinocyte adhesion through disrupted calcium signaling. While traditionally considered a structural defect, recent studies suggest that Th2-mediated inflammation may exacerbate disease pathology. Interleukin (IL)-4 and IL-13, central mediators of type 2 inflammation, have been implicated in barrier dysfunction in other dermatoses, yet their role in HHD remains poorly defined.
This retrospective study employed immunohistochemistry to assess IL-4 and IL-13 expression in lesional skin from patients with HHD (n = 7) compared to age-, sex-, and site-matched atopic dermatitis (AD) controls (n = 6) and healthy control samples (n = 4).
IL-4 expression was significantly elevated in the epidermis of HHD compared to negative control tissue (mean 3966 cells/mm
vs. 808 cells/mm
, p = 0.0219), whereas IL-13 expression was markedly increased in the dermis (mean 5288 cells/mm
vs. 629 cells/mm
, p < 0.0001), relative to healthy controls. No statistically significant difference was observed between AD and HHD samples.
These findings highlight a potential role for IL-4 and IL-13 in the pathogenesis of HHD, supporting the therapeutic relevance for targeting type 2 cytokines. Agents such as dupilumab and potentially JAK inhibitors may offer new avenues for effective disease management.