Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial (original) (raw)
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JAMA dermatology, 2018
Facial angiofibromas occur in approximately 75% of individuals with tuberous sclerosis complex (TSC), causing substantial morbidity and disfigurement. Current therapies are partially effective, uncomfortable, produce scarring, and need repeating to treat recurrence. To evaluate the efficacy and safety of topical rapamycin for TSC-related facial angiofibromas. This prospective, multicenter, randomized, double-blind, vehicle-controlled trial with 6 monthly clinic visits enrolled 179 patients with TSC-related facial angiofibromas not treated within 6 months from May 2012 to March 2014 in 9 clinical sites in the United States and 1 in Australia. Patients were randomized (1:1:1) to topical formulation containing 0.3 g per 30 g (1%) rapamycin, 0.03 g per 30 g (0.1%) rapamycin, or vehicle alone. Participants applied 1.0 mL to designated areas daily at bedtime. Angiofibroma Grading Scale (AGS) change from baseline scored from photographs by independent masked dermatologists. Safety analyses...
Child Neurology Open
Facial angiofibromas, composed of fibrous tissue and blood vessels appearing on the face, are closely associated with tuberous sclerosis complex. Historically, oral rapamycin, a mammalian target of the rapamycin inhibitor of cell proliferation, has been used to treat visceral tuberous sclerosis–related tumors; however, the side effect profile of this medicine generally precludes its use in patients lacking significant internal involvement. The authors developed a novel topical formulation of rapamycin cream to treat the facial angiofibroma without exposing patients to possible systemic side effects. We followed 11 patients in a long-term, open-label, prospective study to evaluate the safety and effectiveness of rapamycin cream when used chronically. All of the patients showed an improvement in the appearance of their facial angiofibroma which was maintained in long-term follow-up without safety concerns or systemic absorption. The novel rapamycin cream was tolerated well by all pati...
Background and Objectives: Facial angiofibromas are disfiguring facial lesions, present in up to 80% of patients with tuberous sclerosis complex. Recent elucidation of the complex cell signaling pathways that are disrupted in tuberous sclerosis indicates that rapamycin may be successful in alleviating the appearance of these lesions. The objectives of the current study were to evaluate the safety of topically applied rapamycin in patients with tuberous sclerosis complex and to determine its potential effectiveness in treatment of facial angiofibromas. Patients and Methods: The study was a prospective, randomized, double-blind, placebo-controlled study performed at the University of Texas Health Science Center at Houston. Study subjects were recruited from the patient populations at the University of Texas Tuberous Sclerosis Center of Excellence. All subjects were over the age of 13 years and had a diagnosis of tuberous sclerosis complex. Subjects were excluded if they were using any...
Plastic and Aesthetic Research, 2016
How to cite this article: Palmetun Ekbäck M, Wiegleb Edström D. Topical rapamycin for angiofibromas in patients with tuberous sclerosis: how does it work in clinical practice? Plast Aesthet Res 2016;3:328-34. Aim: Topical rapamycin for angiofibromas has been reported to be a new promising treatment. This study aims to report the outcome in clinical practice. Methods: A retrospective clinical follow-up on twenty-three patients who had been prescribed an oral solution of 0.1% rapamycin, to be applied on facial lesions once a day. Results: Seventeen of 23 patients continued the treatment. Papules and nodules were improved in 8 patients (47%) and erythema in 12 (70%). Side effects, such as stinging and redness were reported in 35% of patients. Blood samples were taken from 5 patients and no rapamycin could be detected. All patients who paused the treatment relapsed. Conclusion: Topical rapamycin has a positive effect on angiofibromas with improvement in both erythema and papules even if only applied every second to third day, but continuous treatment is needed. ABSTRACT Article history:
Topical rapamycin (sirolimus) for facial angiofibromas
Indian Dermatology Online Journal, 2013
Rapamycin (sirolimus) is a fungal fermentation product that inhibits the proper functioning of a serine/threonine protein kinase in mammalian cells eponymously named mammalian target of rapamycin, or mTOR. Rapamycin is a novel class of anticancer and immunosuppressant drugs targeting the proteins at molecular level. Rapamycin (sirolimus) is routinely incorporated in drug-eluting stents used for cardiac angioplasty. In recent years, rapamycin was found to be efficacious in managing the symptom complex of tuberous sclerosis, i.e. renal angiomyolipoma, giant cell astrocytoma and pulmonary lymphangiomyomatosis. Various investigators have also proved that topically applied rapamycin causes regression of facial angiofibromas, giving better cosmetic results.
Advances in the therapeutic use of mammalian target of rapamycin (mTOR) inhibitors in dermatology
Journal of the American Academy of Dermatology, 2015
Significant developments in the use of mammalian target of rapamycin (mTOR) inhibitors (mTORIs) as immunosuppressant and antiproliferative agents have been made. Recent advances in the understanding of the mTOR signaling pathway and its downstream effects on tumorigenesis and vascular proliferation have broadened the clinical applications of mTORIs in many challenging disorders such as tuberous sclerosis complex, pachyonychia congenita, complex vascular anomalies, and inflammatory dermatoses. Systemic mTORI therapy has shown benefits in these areas, but is associated with significant side effects that sometimes necessitate drug holidays. To mitigate the side effects of systemic mTORIs for dermatologic applications, preliminary work to assess the potential of percutaneous therapy has been performed, and the evidence suggests that percutaneous delivery of mTORIs may allow for effective long-term therapy while avoiding systemic toxicities. Additional large placebo-controlled, double-blinded, randomized studies are needed to assess the efficacy, safety, duration, and tolerability of topical treatments. The objective of this review is to provide updated information on the novel use of mTORIs in the management of many cutaneous disorders.