The Clinical Efficacy and Mechanism of Action of Alitretinoin in the Treatment of Alopecia Areata

Background: Alitretinoin, a pan-retinoid receptor agonist approved for chronic hand eczema, exhibits immunomodulatory effects that may benefit alopecia areata (AA).However, clinical evidence for its use in AA is limited.Objective: To evaluate alitretinoin's clinical efficacy and immunological mechanism in patients with AA.Methods: We reviewed retrospectively twenty-one patients with AA who were treated with alitretinoin, either as monotherapy (n=9) or add-on therapy (n=12).Treatment response was assessed using the Severity of Alopecia Tool (SALT) scores, and in vitro studies used human outer root sheath cells stimulated with interferon-γ and polyinosinic:polycytidylic acid to investigate the drug's effects on inflammatory pathways.Results: Both groups showed significant reductions in SALT scores (p=0.04 and p=0.02, respectively).Patients with baseline SALT scores below 50 demonstrated superior improvement.Adverse events were mild, with headache (33.3%) and cheilitis (4.8%) being the most common.In vitro, alitretinoin suppressed interleukin-6 and tumor necrosis factor-α expression, decreased phosphorylation of signal transducer and activator of transcription (STAT) 1/STAT3, and downregulated major histocompatibility complex class I expression, suggesting restoration of hair follicle immune privilege.Conclusion: Alitretinoin appears to be a safe and potentially effective treatment for patients with mild to moderate AA unresponsive to conventional therapies.Its role as a monotherapy or adjunctive option in selected cases warrants further investigation through larger controlled studies.