PMID- 24910976 OWN - NLM STAT- MEDLINE DCOM- 20151006 LR - 20231110 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 6 DP - 2014 TI - Topical rapamycin as a treatment for fibrofolliculomas in Birt-Hogg-Dube syndrome: a double-blind placebo-controlled randomized split-face trial. PG - e99071 LID - 10.1371/journal.pone.0099071 [doi] LID - e99071 AB - BACKGROUND: Birt-Hogg-Dube syndrome (BHD) is a rare autosomal dominant disorder characterised by the occurrence of benign, mostly facial, skin tumours called fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax and an increased renal cancer risk. Current treatments for fibrofolliculomas have high rates of recurrence and carry a risk of complications. It would be desirable to have a treatment that could prevent fibrofolliculomas from growing. Animal models of BHD have previously shown deregulation of mammalian target of rapamycin (mTOR). Topical use of the mTOR inhibitor rapamycin is an effective treatment for the skin tumours (angiofibromas) in tuberous sclerosis complex, which is also characterised by mTOR deregulation. In this study we aimed to determine if topical rapamycin is also an effective treatment for fibrofolliculomas in BHD. METHODS: We performed a double blinded, randomised, facial left-right controlled trial of topical rapamycin 0.1% versus placebo in 19 BHD patients. Trial duration was 6 months. The primary outcome was cosmetic improvement as measured by doctors and patients. Changes in fibrofolliculoma number and size were also measured, as was occurrence of side effects. RESULTS: No change in cosmetic status of fibrofolliculomas was reported in the majority of cases for the rapamycin treated (79% by doctors, 53% by patients) as well as the placebo treated facial sides (both 74%). No significant differences between rapamycin and placebo treated facial halves were observed (p = 1.000 for doctors opinion, p = 0.344 for patients opinion). No significant difference in fibrofolliculoma number or change in size of the fibrofolliculomas was seen after 6 months. Side effects occurred more often after rapamycin treatment (68% of patients) than after placebo (58% of patients; p = 0.625). A burning sensation, erythema, itching and dryness were most frequently reported. CONCLUSIONS: This study provides no evidence that treatment of fibrofolliculomas with topical rapamycin in BHD results in cosmetic improvement. TRIAL REGISTRATION: ClinicalTrials.gov NCT00928798. FAU - Gijezen, Lieke M C AU - Gijezen LM AD - Department of Dermatology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands. FAU - Vernooij, Marigje AU - Vernooij M AD - Department of Dermatology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands. FAU - Martens, Herm AU - Martens H AD - Department of Dermatology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands. FAU - Oduber, Charlene E U AU - Oduber CE AD - Department of Dermatology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands. FAU - Henquet, Charles J M AU - Henquet CJ AD - Department of Dermatology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands. FAU - Starink, Theo M AU - Starink TM AD - Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands. FAU - Prins, Martin H AU - Prins MH AD - Department of Epidemiology, CAPHRI Research School for Public Health Primary Care, Maastricht University Medical Centre+, Maastricht, The Netherlands. FAU - Menko, Fred H AU - Menko FH AD - Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands. FAU - Nelemans, Patty J AU - Nelemans PJ AD - Department of Epidemiology, CAPHRI Research School for Public Health Primary Care, Maastricht University Medical Centre+, Maastricht, The Netherlands. FAU - van Steensel, Maurice A M AU - van Steensel MA AD - Department of Dermatology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands; Department of Clinical Genetics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands; Institute of Medical Biology, Singapore, Singapore. LA - eng SI - ClinicalTrials.gov/NCT00928798 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140609 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antibiotics, Antineoplastic) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Administration, Topical MH - Adult MH - Aged MH - Antibiotics, Antineoplastic/administration & dosage/adverse effects/*therapeutic use MH - Birt-Hogg-Dube Syndrome/*drug therapy/pathology MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Middle Aged MH - Sirolimus/administration & dosage/adverse effects/*therapeutic use MH - Skin/*drug effects/pathology MH - Skin Neoplasms/*drug therapy/pathology MH - Treatment Outcome PMC - PMC4049818 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/06/10 06:00 MHDA- 2015/10/07 06:00 PMCR- 2014/06/09 CRDT- 2014/06/10 06:00 PHST- 2013/11/22 00:00 [received] PHST- 2014/05/08 00:00 [accepted] PHST- 2014/06/10 06:00 [entrez] PHST- 2014/06/10 06:00 [pubmed] PHST- 2015/10/07 06:00 [medline] PHST- 2014/06/09 00:00 [pmc-release] AID - PONE-D-13-48906 [pii] AID - 10.1371/journal.pone.0099071 [doi] PST - epublish SO - PLoS One. 2014 Jun 9;9(6):e99071. doi: 10.1371/journal.pone.0099071. eCollection 2014.