A Pilot Study to Examine the Efficacy and Tolerability of Sirolimus on Epidermal Nevi Lesions in Patients 6 Years Old and Above.

Epidermal nevi are skin growths that develop because of a genetic change that occurs after conception, meaning only some skin cells are affected. These growths appear as thickened, often darker areas of skin that form lines or swirls. On the arms and legs, they usually appear as straight streaks, while on the trunk and face they follow curved patterns called the lines of Blaschko, which reflect how skin cells develop before birth.

These skin changes are caused by specific genetic changes that turn on certain cell growth pathways inside skin cells. Most linear verrucous epidermal nevi involve one of two major pathways that control cell growth: the PI3K/AKT/mTOR pathway or the RAS/MAPK pathway. In more than 40% of cases, changes in the FGFR3 or PIK3CA genes cause constant activation of the PI3K/AKT/mTOR pathway, leading to excess skin growth.

Sirolimus (also called rapamycin) is a medication that blocks the mTOR pathway, slowing down cell growth and protein production. Medications like this are already used to treat certain cancers caused by overactive mTOR signaling.

Topical sirolimus is FDA-approved as a 0.2% gel (Hyftor) to treat facial angiofibromas in people with tuberous sclerosis complex (TSC). In TSC, genetic changes cause the mTOR pathway to be overly active, leading to skin growths called angiofibromas. Studies have shown that applying sirolimus to the skin can reduce the size and visibility of these lesions.

Inclusion criteria

• Patients 6 years of age or above with a non-inflammatory epidermal nevi
• Lesion(s) that have been present for at least 3 years and are relatively stable
• At least 2 cm in length (ideally continuous, but can be cumulatively)
• The lesions is raised, hyperpigmented compared to the surrounding skin, and is noninflammatory with a physician global assessment (PGA) of at least 3 (moderate).
• Agree to avoid emollient use at the nevus site throughout the study
• Agree to not bath or shower 2 hours post-application, knowing that the gel can be applied after bathing or showering.

Exclusion criteria

• Patients currently or recently (within past 4 weeks) using a topical keratolytic or topical anti-inflammatory medication at the lesional site (i.e. topical steroid, topical retinoid, alpha-OH acid)
• Pregnant or planning to become pregnant during the course of the study