title: A topical combination of rapamycin and tacrolimus for the treatment of angiofibroma due to tuberous sclerosis complex (TSC): a pilot study of nine Japanese patients with TSC of different disease severity.
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.
  
  
  OBJECTIVE
  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.affiliation: 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
authors.forename: M
authors.initials: M
authors.lastname: Wataya-Kaneda
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: I
authors.initials: I
authors.lastname: Katayama
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018322:Angiofibroma / Q000188:drug therapy* / Q000209:etiology; D002648:Child; D004338:Drug Combinations; D005153:Facial Neoplasms / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009824:Ointments; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage; D010865:Pilot Projects; D020123:Sirolimus / Q000008:administration & dosage*; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome; D014402:Tuberous Sclerosis / Q000150:complications*; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D007166:Immunosuppressive Agents; D009824:Ointments; D014677:Pharmaceutical Vehicles; D020123:Sirolimus; D016559:Tacrolimus