Abstract
This review summarizes the off-label applications of topical sirolimus (rapamycin) for dermatological conditions beyond its approved use for angiofibromas associated with tuberous sclerosis, focusing on efficacy, safety, and reported adverse effects. Off-label use of mammalian target of rapamycin inhibitors like sirolimus has shown promising potential in dermatology. We analyzed the literature on the efficacy and safety of topical sirolimus for a range of dermatological conditions, including inflammatory eruptions, genodermatoses, bullous disorders, neoplasms, and others. Publications on topical sirolimus for other vascular anomalies, such as lymphatic malformations, were excluded to maintain focus on other lesser-known dermatological uses, except for studies involving post-laser combination therapies for vascular lesions. Topical sirolimus demonstrated notable efficacy in several genetic and benign proliferative skin disorders, including pachyonychia congenita, trichilemmomas, trichoepitheliomas, and Kaposi sarcoma, with a generally favorable safety profile and minimal systemic absorption. However, variability in formulations, dosing regimens, and the predominance of small-scale studies limit definitive conclusions. Further research is warranted to standardize treatment protocols and validate these findings.