Molecular Changes Induced by Carbon Dioxide Laser in Hailey‐Hailey Disease: A Potential Mechanism Underlying Treatment Efficacy

ABSTRACT Introduction Hailey‐Hailey disease (HHD) is a rare genodermatosis caused by mutations in the ATP2C1 gene that codes for SPCA1, a calcium transporter in the epidermis. HHD impairs quality of life, and no curative treatment exists. Methods To confirm the efficacy and safety of CO 2 laser in HHD, we conducted a randomized, prospective, controlled study that included 10 patients with histologically confirmed HHD. A 4‐mm punch biopsy was taken from unaffected skin and the laser‐treated area before treatment. CO 2 laser treatment was performed under sedation, and after 6 months, new biopsies were taken at the same sites. Samples were used to extract RNA and analyze potential changes in gene expression. Results Laser treatment provided a significant reduction in the lesioned area ( p < 0.002). Gene expression analysis revealed reduced ATP2C1 expression in lesional skin and high expression of genes related to keratinocyte proliferation and IL‐17‐dependent inflammation. Interestingly, in affected skin after laser treatment, there was an enhancement of ATP2C1 with a reduced expression of genes related to keratinocyte proliferation and IL‐17‐dependent inflammation. Conclusions CO 2 laser is safe and effective in HHD. A plausible explanation could be molecular changes after treatment, especially ATP2C1 enhancement and IL‐17‐dependent inflammation decreased.