Gijezen Lieke M C, Vernooij Marigje, Martens Herm, Oduber Charlene E U, Henquet Charles J M, Starink Theo M, Prins Martin H, Menko Fred H, Nelemans Patty J, van Steensel Maurice A M
Department of Dermatology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands.
PLoS One. 2014 Jun 9;9(6):e99071. doi: 10.1371/journal.pone.0099071. eCollection 2014.
Birt-Hogg-Dubé 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.
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.
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.
This study provides no evidence that treatment of fibrofolliculomas with topical rapamycin in BHD results in cosmetic improvement.
ClinicalTrials.gov NCT00928798.
Birt-Hogg-Dubé综合征（BHD）是一种罕见的常染色体显性疾病，其特征为出现良性的、大多位于面部的皮肤肿瘤，即纤维毛囊瘤，还有多个肺囊肿、自发性气胸以及肾癌风险增加。目前针对纤维毛囊瘤的治疗复发率高且有并发症风险。若能有一种可防止纤维毛囊瘤生长的治疗方法将是很理想的。BHD的动物模型此前已显示雷帕霉素哺乳动物靶点（mTOR）失调。局部使用mTOR抑制剂雷帕霉素是结节性硬化症皮肤肿瘤（血管纤维瘤）的有效治疗方法，结节性硬化症同样以mTOR失调为特征。在本研究中，我们旨在确定局部使用雷帕霉素对BHD中的纤维毛囊瘤是否也是一种有效治疗方法。
我们对19例BHD患者进行了一项双盲、随机、面部左右对照试验，比较0.1%局部雷帕霉素与安慰剂。试验持续时间为6个月。主要结局是由医生和患者评估的美容改善情况。还测量了纤维毛囊瘤数量和大小的变化以及副作用的发生情况。
在大多数病例中，雷帕霉素治疗的面部（医生评估为79%，患者评估为53%）以及安慰剂治疗的面部（均为74%），纤维毛囊瘤的美容状态均未改变。雷帕霉素治疗的面部与安慰剂治疗的面部之间未观察到显著差异（医生意见p = 1.000，患者意见p = 0.344）。6个月后，纤维毛囊瘤数量或大小变化均未观察到显著差异。雷帕霉素治疗后副作用发生频率（68%的患者）高于安慰剂（58%的患者；p = 0.625）。最常报告的是烧灼感、红斑、瘙痒和干燥。
本研究没有证据表明BHD中局部使用雷帕霉素治疗纤维毛囊瘤能带来美容改善。
ClinicalTrials.gov NCT00928798
