Characterization and Management of Facial Angiofibroma Related to Tuberous Sclerosis Complex in the United States: Retrospective Analysis of the Natural History Database

Abstract Background: Facial angiofibroma is the most predominant cutaneous manifestation of tuberous sclerosis complex (TSC), a rare autosomal dominant genetic disorder impacting the mechanistic target of rapamycin (mTOR). Facial angiofibroma can bleed spontaneously, impair eyesight, and cause aesthetic disfiguration causing psychological and social stress. To date, there is little or no evidence on the demographics, and other TSC features associated with facial angiofibroma or the use of mTOR inhibitor for the management of facial angiofibroma. This is a retrospective study of TSC Alliance’s Natural History Database aimed to characterize facial angiofibroma and to evaluate features associated with a higher risk of facial angiofibroma or the use of topical mTOR inhibitors for management of facial angiofibroma. Data in the NHD was obtained from 18 clinical sites in the US since 2006.Results: Of the 2240 patients, 2088 patients were enrolled in the US and data from 2057 patients were included in this analysis. Patient features associated with a higher risk of facial angiofibroma or the use of topical mTOR inhibitors. Facial angiofibroma was noted in 1329 (64.4%) patients with TSC. Patients with facial angiofibroma were older on average. TSC2 mutation was more common, and the burden of other TSC-related manifestations was significantly higher in patients with facial angiofibroma. The 6–17 and the 18–45 -year-old age groups, TSC2 mutation, angiomyolipoma, and renal cysts were significantly associated with a higher risk of facial angiofibroma. Topical mTOR inhibitor use was noted for 329 (24.8%) patients with facial angiofibroma. Being white and presence of angiomyolipoma were significantly associated with higher use of a topical mTOR inhibitor.CONCLUSIONS: Patients with facial angiofibroma were older and more commonly had a TSC2 mutation. The higher burden of TSC-related manifestations in patients with facial angiofibroma illustrates the importance of accurate diagnosis by dermatologists and referral to a comprehensive multi-disciplinary TSC Clinic for surveillance and management of other TSC manifestations. About one-fourth of patients with facial angiofibroma used a topical mTOR inhibitor.