Evaluating the Safety and Efficacy of Sirolimus Topical Gel 0.2% to Treat Acanthosis Nigricans

BACKGROUND: There are currently no FDA-approved pharmacologic treatments for acanthosis nigricans (AN), a common dermatologic condition characterized by hyperpigmented, velvety plaques. AN disproportionately affects individuals with skin of color and is often associated with insulin resistance and obesity. There is a need for effective, safe, and well-tolerated treatments for AN. OBJECTIVE: To evaluate the safety and efficacy of sirolimus gel 0.2% in improving pigmentation, skin texture, and quality of life in patients with AN. METHODS: In this investigator-initiated, single-center, 12-week phase 2 pilot study, five adults with AN on the posterior neck applied sirolimus gel 0.2% twice daily. Assessments were conducted at baseline and weeks 4, 8, and 12. Efficacy was evaluated using a narrowband reflectance spectrophotometer and colorimeter to assess Melanin Index (M-index), Acanthosis Nigricans Scoring Chart (ANSC), Dermatology Life Quality Index (DLQI), Patient and Investigator Global Evaluations (PGE and IGE), and Treatment Satisfaction Questionnaire for Medication (TSQM). Safety and tolerability were monitored. RESULTS: At week 12, participants demonstrated a significant reduction in pigmentation, with a 19.7% ± 4.9% decrease in M-index (P=0.0037) and a 30.2% reduction in ANSC scores (P=0.0011). Improvements were observed as early as week 4. DLQI scores improved significantly from baseline (P=0.0086). No serious adverse events occurred; mild application-site dryness and erythema were the only reported side effects. CONCLUSION: Sirolimus gel 0.2% was safe and effective for AN, producing early improvements in pigmentation, texture, and patient-reported outcomes. Larger randomized controlled trials are warranted to validate these findings.  .