In synthetic analogues, such as etretinate, acitretin, or tazarotene, a benzene ring substitutes the cyclohexane. The term “retinoid” concerns both natural and synthetic analogues of vitamin A. As an isoprenoid, it is characterized by a hydrocarbon chain containing an ending hydroxyl. Vitamin A (or retinol, a diterpene), a cardinal micronutrient in human metabolism, is a lipophilic molecule composed by isoprene units. Finally, we are hypothesizing future perspectives in the treatment of non-melanoma skin cancers, fungal infections, photoaging, and hand-foot skin reactions with trifarotene. No high-quality randomized clinical trials have evaluated the treatment of primary cutaneous lymphomas with trifarotene. Randomized trials evaluating trifarotene tolerability, safety, and efficacy in congenital ichthyosis and acne have demonstrated great results and mild side effects, leading to the approval by the FDA of trifarotene for the treatment of lamellar ichthyosis in 2014, and of acne vulgaris in October 2019. Only articles published in English language were included. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, ) from 2012 to today and reference lists of respective articles.

In this review, we reported the trials-both concluded and in progress-including the use of trifarotene in dermatological diseases. Trifarotene is a new fourth-generation retinoid with a selective action on RAR-γ. Retinoids have now reached the fourth generation, progressively reducing toxicity whilst increasing their efficacy. Retinoids have numerous applications in inflammatory, dyskeratotic, and oncohematology diseases.

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