Successful treatment of angiofibromata of tuberous sclerosis complex with rapamycin

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome manifesting as hamartomatous growths in multiple organs. We present two cases of patients with TSC and associated facial angiofibromata treated with topical and oral rapamycin and discuss the role for rapamycin in the treatment of these disfiguring lesions. Our patients demonstrated decreased numbers of angiofibromata and less redness with this treatment. This is the first published report on the use of topical rapamycin for the treatment of angiofibromata.

Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial

“…However, the oral rapamycin solution that we used in this study has been shown to be an effective topical treatment for angiofibromas in TSC, without detectable levels of rapamycin in the serum [26]. A 1∶1 mixture of rapamycin solution 1 mg/ml in an emollient has also shown to be effective in TSC [27]. This indicates that rapamycin in this oral solution penetrates into the skin and that the concentration of rapamycin we used is sufficient to cause a clinical effect.…”

Treatment of Angiofibromas in Tuberous Sclerosis Complex: The Effect of Topical Rapamycin and Concomitant Laser Therapy

“…Since Haemel et al [6] first reported improvement of facial angiofibromas after applying 1% rapamycin ointment twice daily, several papers have reported the use of topical rapamycin to treat facial angiofibromas [2,3,4,5,6,7,8,9,10,11] (table 1). Although varying levels of improvement were recorded in the previous studies, most reported no significant systemic or local side effects during the treatment period (6 weeks to 9 months).…”

“…The concentration, vehicle material, application frequency and total treatment period differed among the studies. With regard to the concentration of ointment or solution, all previous studies reported clinical improvement with concentrations ranging from 0.003 to 1.0% in different vehicles [2,3,4,5,6,7,8,9,10,11]. Foster et al [7] demonstrated that topical rapamycin treatment had the same effect whether it was in an ointment base or in a water base, although the ointment base caused less skin irritation than the water base.…”

“…The recent technological development of an ointment base for specific material would be required to find the best vehicle material for the topical rapamycin ointment. With respect to application frequency, daily once or twice was common, application by 3 times weekly was also tried [2,3,4,5,6,7,8,9,10,11]. …”

“…This treatment is painless, and easy to perform compared to all present invasive treatment options including laser treatment. However, the observation periods in these previous studies were fairly short with most of them less than 6 months, and the employed methods such as concentrations of the drug and how to apply it to the skin are different according to the authors [2,3,4,5,6,7,8,9,10,11]. …”