M Wataya-Kaneda1, M Tanaka, A Nakamura, S Matsumoto, I Katayama. 1. Department of Dermatology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. mkaneda@derma.med.osaka-u.ac.jp
Abstract
BACKGROUND: Dysregulation of mTOR signalling by mutations in tuberin and/or hamartin leads to the formation of tuberous sclerosis complex (TSC). Trials to treat TSC using mTOR inhibitors, including rapamycin, have been performed. Although rapamycin improves many TSC lesions, significant side-effects appear after systemic administration. Topical administration has been recommended. OBJECTIVES: The efficacy of rapamycin-tacrolimus ointment was examined for TSC-related angiofibroma. METHODS: Left-right comparisons of the tacrolimus ointments with/without 0·2% rapamycin was conducted in symmetrical facial angiofibromas in nine patients with definitive TSC. After the 3-month treatment, a cumulative score for redness, flatness and papule size was used to evaluate the efficacy of the treatment. Blood rapamycin levels were analysed by liquid chromatography-electrospray mass spectrometry (LC-ESI/MS). RESULTS: At the end of the treatment, all of the scores significantly improved for rapamycin-tacrolimus treatment compared with tacrolimus alone. No adverse reactions were noted and blood levels of rapamycin were below the detection limit in all cases. CONCLUSIONS: Topical application of rapamycin-tacrolimus ointment is a safe and useful treatment for TSC-related angiofibroma.
BACKGROUND: Dysregulation of mTOR signalling by mutations in tuberin and/or hamartin leads to the formation of tuberous sclerosis complex (TSC). Trials to treat TSC using mTOR inhibitors, including rapamycin, have been performed. Although rapamycin improves many TSC lesions, significant side-effects appear after systemic administration. Topical administration has been recommended. OBJECTIVES: The efficacy of rapamycin-tacrolimus ointment was examined for TSC-related angiofibroma. METHODS: Left-right comparisons of the tacrolimus ointments with/without 0·2% rapamycin was conducted in symmetrical facial angiofibromas in nine patients with definitive TSC. After the 3-month treatment, a cumulative score for redness, flatness and papule size was used to evaluate the efficacy of the treatment. Blood rapamycin levels were analysed by liquid chromatography-electrospray mass spectrometry (LC-ESI/MS). RESULTS: At the end of the treatment, all of the scores significantly improved for rapamycin-tacrolimus treatment compared with tacrolimus alone. No adverse reactions were noted and blood levels of rapamycin were below the detection limit in all cases. CONCLUSIONS: Topical application of rapamycin-tacrolimus ointment is a safe and useful treatment for TSC-related angiofibroma.
Authors: Mary Kay Koenig; Adelaide A Hebert; Joan Roberson; Joshua Samuels; John Slopis; Audrey Woerner; Hope Northrup Journal: Drugs R D Date: 2012-09-01
Authors: Lieke M C Gijezen; Marigje Vernooij; Herm Martens; Charlene E U Oduber; Charles J M Henquet; Theo M Starink; Martin H Prins; Fred H Menko; Patty J Nelemans; Maurice A M van Steensel Journal: PLoS One Date: 2014-06-09 Impact factor: 3.240