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Abstract：
BACKGROUND: 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.
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.
BACKGROUND: ClinicalTrials.gov NCT00928798.
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.
BACKGROUND: ClinicalTrials.gov NCT00928798.
摘要：
背景：Birt-Hogg-Dubé综合征（BHD）是一种罕见的常染色体显性疾病，其特征是良性，主要是面部,皮肤肿瘤称为纤维囊瘤，多发性肺囊肿,自发性气胸和肾癌风险增加。纤维囊瘤的当前治疗具有高复发率并且具有并发症的风险。希望有一种可以防止纤维叶瘤生长的治疗方法。BHD的动物模型先前已显示哺乳动物雷帕霉素靶蛋白(mTOR)的失调。局部使用mTOR抑制剂雷帕霉素是结节性硬化症中皮肤肿瘤（血管纤维瘤）的有效治疗方法。其特征还在于mTOR放松管制。在这项研究中，我们旨在确定局部雷帕霉素是否也是BHD纤维囊瘤的有效治疗方法。
方法：我们进行了双盲，随机化，在19例BHD患者中使用0.1%局部雷帕霉素与安慰剂的面部左右对照试验。试验时间为6个月。主要结果是医生和患者测量的美容改善。还测量了纤维囊瘤数量和大小的变化，副作用的发生也是如此。
结果：在接受雷帕霉素治疗的大多数病例中，纤维囊瘤的美容状态没有变化（79%由医生报告，53％的患者）以及安慰剂治疗的面部侧（均为74％）。观察到雷帕霉素和安慰剂治疗的面部半部之间没有显着差异（医生意见p=1.000，患者意见p=0.344)。6个月后，纤维囊瘤的数量或大小变化均无显着差异。雷帕霉素治疗后的副作用（68％的患者）比安慰剂治疗后（58％的患者；p=0.625）更常见。一种灼热的感觉，红斑,瘙痒和干燥是最常见的报道。
结论：这项研究没有提供证据表明，局部用雷帕霉素治疗BHD的纤维叶瘤可改善美容效果。
背景：ClinicalTrials.govNCT00928798。
方法：我们进行了双盲，随机化，在19例BHD患者中使用0.1%局部雷帕霉素与安慰剂的面部左右对照试验。试验时间为6个月。主要结果是医生和患者测量的美容改善。还测量了纤维囊瘤数量和大小的变化，副作用的发生也是如此。
结果：在接受雷帕霉素治疗的大多数病例中，纤维囊瘤的美容状态没有变化（79%由医生报告，53％的患者）以及安慰剂治疗的面部侧（均为74％）。观察到雷帕霉素和安慰剂治疗的面部半部之间没有显着差异（医生意见p=1.000，患者意见p=0.344)。6个月后，纤维囊瘤的数量或大小变化均无显着差异。雷帕霉素治疗后的副作用（68％的患者）比安慰剂治疗后（58％的患者；p=0.625）更常见。一种灼热的感觉，红斑,瘙痒和干燥是最常见的报道。
结论：这项研究没有提供证据表明，局部用雷帕霉素治疗BHD的纤维叶瘤可改善美容效果。
背景：ClinicalTrials.govNCT00928798。
