The untapped potential of oral vitamin E in lichen sclerosus: from immunobiology to real-life clinical experience.

Lichen sclerosus (LS) is a chronic dermatosis characterized by persistent inflammation, progressive fibrosis, and an elevated risk of vulvar squamous cell carcinoma. While ultra-potent topical corticosteroids remain the gold standard of care, the necessity for long-term maintenance therapy raises concerns regarding cumulative toxicity, underscoring the critical need for adjunctive therapies that target underlying pathogenic mechanisms. Vitamin E, traditionally recognized for its antioxidant and membrane-protective properties, has emerged as a promising candidate due to its broad immunomodulatory effects, including its regulatory impact on innate and adaptive immunity and its anti-inflammasome activity. However, the available clinical evidence remains limited to topical formulations, and corresponding efficacy data are scarce. In this Perspective article, we critically analyze the current clinical evidence on oral vitamin E in LS, delineate its immunological mechanisms, and incorporate insights from real-world clinical practice at a tertiary referral center, which should be interpreted as hypothesis-generating given the observational, uncontrolled design. Furthermore, we explore the potential of oral vitamin E formulations, address the pharmacokinetic challenges associated with conventional delivery, and propose future research avenues-such as optimized delivery systems and active metabolite formulations-to fully elucidate the therapeutic role of oral vitamin E in LS management.