title: Improvement of tuberous sclerosis complex (TSC) skin tumors during long-term treatment with oral sirolimus.
abstract: BACKGROUND
  Oral mechanistic target of rapamycin inhibitors have been shown to reduce visceral tumor volume in patients with tuberous sclerosis complex (TSC).
  
  
  OBJECTIVE
  We sought to evaluate the cutaneous response to oral sirolimus in patients with TSC and an indication for systemic treatment, including long-term effects.
  
  
  METHODS
  A retrospective analysis of 14 adult patients with TSC prescribed sirolimus to treat lymphangioleiomyomatosis was performed. Serial photographs of angiofibromas, shagreen patches, and ungual fibromas taken before, during, and after the treatment period were blinded, then assessed using the Physician Global Assessment of Clinical Condition (PGA). Microscopic and molecular studies were performed on skin tumors harvested before and during treatment.
  
  
  RESULTS
  Sirolimus significantly improved angiofibromas (median treatment duration 12 months; median PGA score 4.5 [range 1.5-5]; Wilcoxon signed rank test, P = .018) and shagreen patches (median treatment duration 10 months; median PGA score 4.5 [range 3.5-5]; Wilcoxon signed rank test, P = .039), whereas ungual fibromas improved in some patients (median treatment duration 6.5 months; median PGA score 4.66 [range 2.75-5]; Wilcoxon signed rank test, P = .109). Clinical, immunohistochemical, or molecular evidence of resistance was not observed (range 5-64 months of treatment).
  
  
  CONCLUSIONS
  This was a retrospective analysis limited to adult women with lymphangioleiomyomatosis.
  
  
  CONCLUSIONS
  Oral sirolimus is an effective long-term therapy for TSC skin tumors, particularly angiofibromas, in patients for whom systemic treatment is indicated.
authors.affiliation: Department of Dermatology, Uniformed Services University of Health Sciences, Bethesda, Maryland; Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Neera
authors.initials: N
authors.lastname: Nathan
authors.affiliation: Department of Dermatology, Uniformed Services University of Health Sciences, Bethesda, Maryland.
authors.forename: Ji-an
authors.initials: JA
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Uniformed Services University of Health Sciences, Bethesda, Maryland.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Li
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Cowen
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mary
authors.initials: M
authors.lastname: Haughey
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
authors.affiliation: Department of Dermatology, Uniformed Services University of Health Sciences, Bethesda, Maryland. Electronic address: thomas.darling@usuhs.edu.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Darling
mesh_terms: D000152:Acne Vulgaris / Q000139:chemically induced; D000284:Administration, Oral; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D019226:Oral Ulcer / Q000139:chemically induced; D012189:Retrospective Studies; D038601:Ribosomal Protein S6 / Q000032:analysis; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome; D014402:Tuberous Sclerosis / Q000188:drug therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D038601:Ribosomal Protein S6; D020123:Sirolimus
keywords: angiofibromas; lymphangioleiomyomatosis; mechanistic target of rapamycin inhibitor; shagreen patch; sirolimus; tuberous sclerosis complex; ungual fibroma