Topical use of mammalian target of rapamycin inhibitors in dermatology: A systematic review with meta-analysis.

BACKGROUND:Systemic mammalian target of rapamycin (mTOR) inhibitors are currently used in many dermatologic indications. Their topical use is recent and poorly codified. OBJECTIVE:To provide an overview of the topical use of mTOR inhibitors in dermatologic conditions and evaluate their efficacy and safety. METHODS:A literature search was performed in January 2017. Reports of all studies investigating the use of topical mTOR inhibitors in any dermatology diseases were included. The exclusion criteria were systemic use and mucosal administration. RESULTS:We included 40 studies with a total of 262 patients. In all, 11 dermatologic conditions were found, the most frequent being angiofibromas linked to tuberous sclerosis complex (157 patients). Topical mTOR inhibitors were significantly more efficient than placebo for angiofibromas (relative risk, 2.52; 95% confidence interval, 1.27-5.00; I2 = 0%). The median concentration of sirolimus was 0.1%, with a median treatment duration of 12 weeks. Topical mTOR inhibitors were well tolerated, with only mild or moderate local side effects (mostly irritative) reported. Blood level of sirolimus was not detected in 90% of patients. LIMITATIONS:High heterogeneity in most studies. CONCLUSION:This systematic review supports the efficacy of topical sirolimus for angiofibromas linked to tuberous sclerosis complex, with only local side effects reported. Other indications require further research.