Treatment Landscape for Epidermolysis Bullosa Simplex: A Review of Established and Emerging Therapies

Epidermolysis bullosa (EB) is a group of rare genetic blistering skin diseases, with EB simplex (EBS) being the most common subtype, accounting for around 70% of cases. Although there is no cure for EB, recent advancements led to the historic FDA-approvals of two treatments for dystrophic and junctional EB in 2023 and a third for dystrophic EB in 2025. However, no approved treatments exist for EBS despite its relative prevalence. Here, we outline established and emerging therapies for EBS. Supportive EBS management focuses on five key areas: skin-directed wound care, sweating reduction, keratoderma management, EBS-severe specific considerations, and blister reduction/prevention. Environmental measures target friction and moisture control to prevent blistering with the proper socks, footwear, and ambulation assistive device use. Wound care strategies include draining blisters without unroofing, nonstick dressing protection, and dilute vinegar or bleach baths to prevent infection and mitigate itch. Absorptive powders, glycopyrrolate, oxybutynin, and botulinum toxin target hyperhidrosis reduction. Painful keratoderma management, while challenging, includes mechanical debridement and topical keratolytic agents; targeted treatments including topical sirolimus have been explored in early phase study. A number of emerging treatments targeting EBS inflammatory pathways under investigation include apremilast, dapsone, diacerein ointment, deucravacitinib, and topical broccoli sprout extract. Tetracycline antibiotics are commonly used off-label for blister prevention. Ongoing bench research and gene-editing techniques like siRNA, TALEN, and CRISPR-Cas9 offer hope for translational advancements.