Background: Facial angiofibromas (FAs) are common skin manifestations of tuberous sclerosis complex (TSC) that occur in up to 80% of patients. Rapamycin seems to be effective in decreasing FAs. Objective: The aim of our study was to investigate the efficacy and safety of topically applied rapamycin in TSC patients with FAs. Methods: The methods and the results were carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. PubMed/MEDLINE, SCOPUS, and Cochrane database were systematically searched until April 21, 2022, using the PICO tool (Patient, Interventions, Comparisons, Outcome). Studies regarding efficacy and/or safety of topical sirolimus for the treatment of FAs in TSC with a published full-text in English were included. Safety was assessed based on adverse effects and sirolimus’ blood levels, and efficacy was documented by clinical improvement and reduction of Facial Angiofibroma Severity Index (FASI). For Meta-analysis, Review Manager (RevMan) 5.4.1 software was used, using random-effects model and standardized mean difference (SMD) with 95% confidence interval (CI). Results: Twenty-one final studies were included. Regarding safety, in the included studies the observed adverse effects were mainly local, while the blood levels of rapamycin were within safe limits, decreasing the likelihood of systemic immunosuppression. The meta-analysis revealed a statistically significant decrease in post-treatment FASI (SMD: -1.31, 95% CI: [-1.85,-0.77], p-value <0.00001). Subgroup and sensitivity analyses indicated similar findings. No publication bias was found to this association. Conclusion: The application of topical sirolimus to FAs can safely decrease their severity in patients with TSC.

Aim: Isotretinoin, the drug of choice for severe - nodulocystic acne, might be associated with an increase in insulin resistance. We aimed to investigate this association. Methods: We performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. A systematic search in PubMed/MEDLINE, SCOPUS and Cochrane databases was conducted until the 12th of January 2022 using the PICO tool (Patient, Intervention, Comparison, Outcome). Studies with a published full text in English regarding acne patients under isotretinoin were included. Insulin, glucose and adiponectin serum levels before and after isotretinoin treatment were recorded and insulin sensitivity was assessed using the homeostasis model assessment of insulin resistance (HOMA–IR). For Meta-analysis, the Review Manager (RevMan) 5.4.1 software was utilized. The quality assessment of the included studies was performed using the ROBINS-I tool. Results: Fifteen studies were included. The meta-analysis revealed a statistically significant increase in post-treatment adiponectin [SMD = 0.86; 95% confidence interval (CI) = 0.48 - 1.25, p-value <0.0001; I2 = 58%]. Subgroup analysis by study type revealed the same results [cohort studies pooled SMD = 1.2, 95% CI = 0.81 -1.61, p-value <0.00001; I2 = 8% and case-control studies pooled SMD = 0.53, 95% CI = 0.16 - 0.9, p-value=0.005; I2 = 27%)]. No statistically significant results were shown for insulin, glucose levels and HOMA-IR. Conclusion: Although isotretinoin exposure is not clearly associated with insulin resistance, it seems that it can increase serum adiponectin levels. Further research is needed to clarify this association.