Somatic forward (nonrevertant) mosaicism in recessive dystrophic epidermolysis bullosa.

angiofibromas.4 Successful treatment of nonangiofibroma cutaneous manifestations of TSC has been sparse. To our knowledge, topical rapamycin has not been used successfully to treat the ungual fibromas of TSC. In our case, the use of topical rapamycin was well tolerated and resulted in the resolution of subungual tumors and rapid normalization of the overlying nail distortion. The pathogenesis of TSC is characterized by an autosomal dominantmutation in TSC1 or TSC2 resulting in aberrant functioningofhamartinor tuberin, respectively.Tuberin, aGTPase-activatingproteinforRheb, functions inacomplexformed with hamartin. Rheb, which in turn activatesmTOR, is inhibited in the presence of a normal tuberin-hamartin complex.5 In TSC, the hamartin-tuberin complex is unable to form, resulting in the constitutive activation of the mitogenic mTOR pathway.Rapamycin suppresses this pathway through thedirect inhibition of mTOR. While not entirely understood, an unrestrained mTOR pathway leads toupregulationof vascular endothelial growth factor (VEGF). It is suggested that rapamycin may exert its therapeutic effect onTSC lesionsbydirectlykilling tumor cells inadditionto inhibitingVEGFproduction.6Therefore, thesame mechanism by which rapamycin reduces facial angiofibromas may also apply to nonangiofibroma cutaneous manifestations such as ungual tumors. Patients with periungual and subungual fibromas associatedwithTSCareoftenquite symptomatic andoftenhave significant distortion of the nail plate. Their treatment options have been quite limited to date.While further study is necessary, the experiencewith our patient suggests that topical rapamycin is a safe, well-tolerated, and potentially efficacious treatment forpatientswithungual tumorsassociatedwithTSC.