Analysis of current data on the use of topical rapamycin in the treatment of facial angiofibromas in Tuberous Sclerosis Complex

Abstract

Topical rapamycin can be considered a safe option for the treatment and the prevention of facial angiofibromas in younger patients, but the best formulation has not been established. Our review demonstrates that ointment and gel should be preferred, but it is not clear which concentration is optimal. Long-term and comparative studies between topical rapamycin and ablative techniques are required to establish which treatment has a better outcome and lower recurrence rate.

Cutaneous manifestations of tuberous sclerosis complex and the paediatrician's role

“…36 Treatment was associated with moderate to complete clearance of lesions in 94% of the cases identified. Furthermore, no recurrences were seen with continued use; the longest treatment duration was 30 months.…”

“…Studies demonstrate that topical mTOR inhibitors are effective for the management of several TSC skin lesions; [36][37][38][39][40] however, no formulation is currently commercially available.…”

Comparative Effects of Topical 0.2% Sirolimus for Angiofibromas in Adults and Pediatric Patients with Tuberous Sclerosis Complex

“…Among the hamartomatous skin lesions, facial angiofibromas occur in 80% of patients with TSC [2]. Although angiofibromas are usually asymptomatic, they can be cosmetically disfiguring, thus significantly affecting the quality of life [3]. Moreover, it is known to cause a negative psychological effect on pediatric patients with angiofibromas, especially between the ages of 2 and 5 years [2].…”

“…Sirolimus is an mTOR inhibitor, which is known to inhibit tumorigenesis activity in TSC [3]. Although the oral administration of sirolimus is effective in reducing tumor growths, many side effects can develop, such as leukopenia, thrombocytopenia, anemia, hypercholesterolemia, and hypertriglyceremia.…”

Formulation and characterization of a 0.1% rapamycin cream for the treatment of Tuberous Sclerosis Complex-related angiofibromas

“…Rapamycin concentration in the 38 cream was tested by HPLC and confirmed that it remained above 95% of the initial 39 For the last five years, more than ten formulations have been reported in different 68 pharmaceutical forms (ointment, creams, solutions, etc) at different concentrations 69 (0.003% -1%), from crushed tablets to oral solution, which are not optimal for their 70 tolerance and efficacy. However, all authors described patient improvement, with 71 minimal side effects (except with the solutions), inconsistent percutaneous absorption 72 and systemic diffusion, but recorded recurrence shortly after stopping treatment 73 (Madke et al, 2013;Balestri et al, 2015;Bouguéon et al, 2015). 74 We therefore decided to develop a topical treatment and focused our research on three 75 aspects.…”