Advertisement

Topical Everolimus for Facial Angiofibromas in the Tuberous Sclerosis Complex. A First Case Report

      Abstract

      Background

      Facial angiofibromas are present in most of the patients with the tuberous sclerosis complex and may cause severe disfiguration of the face. The tumor growth in tuberous sclerosis complex is promoted by the disinhibition of the mammalian target of rapamycin pathway. Thus, the systemic treatment with mammalian target of rapamycin inhibitors such as sirolimus and everolimus has recently been established to treat specific tuberous sclerosis complex–associated lesions. For patients who suffer from disfiguring facial angiofibromas only, there is a need for a topical use of mammalian target of rapamycin inhibitors. Sirolimus has been shown to be beneficial in treating facial angiofibromas. But the topical use of everolimus, which has the approval to treat tuberous sclerosis complex–associated tumors, namely giant cell astrocytomas and renal angiofibromas, has not been reported.

      Patients and Results

      We present a 10-year-old girl whose facial angiofibromas were successfully treated with an everolimus ointment without relevant side effects. In addition, we provide a short pharmacological overview of sirolimus and everolimus with focus on the topical use.

      Conclusions

      Topical everolimus seems to be a favorable and safe option for patients with facial angiofibromas who do not require systemic treatment.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Pediatric Neurology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Osborne J.P.
        • Jones A.C.
        • Burley M.W.
        • et al.
        Non-penetrance in tuberous sclerosis.
        Lancet. 2000; 355: 1698
        • Huang J.
        • Manning B.D.
        The TSC1-TSC2 complex: a molecular switchboard controlling cell growth.
        Biochem J. 2008; 412: 179-190
        • Franz D.N.
        • Belousova E.
        • Sparagana S.
        • et al.
        Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial.
        Lancet. 2012; 381: 125-132
        • Bissler J.J.
        • Kingswood J.C.
        • Radzikowska E.
        • et al.
        Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial.
        Lancet. 2013; 381: 817-824
      1. FDA Drug Approval and Databases: Everolimus for Tuberous Sclerosis Complex (TSC). Available at: http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm317490.htm. Accessed September 24, 2013.

      2. FDA Drug Approval and Databases: Everolimus 2012. Available at: http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm302081.htm. Accessed September 24, 2013.

      3. Swissmedic Prodcur Information Votubia. Available at: http://www.swissmedicinfo.ch. Accessed September 24, 2013.

        • Tanaka M.
        • Wataya-Kaneda M.
        • Nakamura A.
        • Matsumoto S.
        • Katayama I.
        First left-right comparative study of topical rapamycin vs. vehicle for facial angiofibromas in patients with tuberous sclerosis complex.
        Br J Dermatol. 2013; 169: 1314-1318
        • Wheless J.W.
        • Almoazen H.
        A novel topical rapamycin cream for the treatment of facial angiofibromas in tuberous sclerosis complex.
        J Child Neurol. 2013; 28: 933-936
        • Kaufman McNamara E.
        • Curtis A.R.
        • Fleischer Jr., A.B.
        Successful treatment of angiofibromata of tuberous sclerosis complex with rapamycin.
        J Dermatolog Treat. 2012; 23: 46-48
        • Koenig M.K.
        • Hebert A.A.
        • Roberson J.
        • et al.
        Topical rapamycin therapy to alleviate the cutaneous manifestations of tuberous sclerosis complex: a double-blind, randomized, controlled trial to evaluate the safety and efficacy of topically applied rapamycin.
        Drugs R D. 2012; 12: 121-126
        • Truchuelo T.
        • Díaz-Ley B.
        • Ríos L.
        • Alcántara J.
        • Jaén P.
        Facial angiofibromas treated with topical rapamycin: an excellent choice with fast response.
        Dermatol Online J. 2012; 18: 15
        • Wataya-Kaneda M.
        • Tanaka M.
        • Nakamura A.
        • Matsumoto S.
        • Katayama I.
        A novel application of topical rapamycin formulation, an inhibitor of mTOR, for patients with hypomelanotic macules in tuberous sclerosis complex.
        Arch Dermatol. 2012; 148: 138-139
        • DeKlotz C.M.
        • Ogram A.E.
        • Singh S.
        • Dronavalli S.
        • MacGregor J.L.
        Dramatic improvement of facial angiofibromas in tuberous sclerosis with topical rapamycin: optimizing a treatment protocol.
        Arch Dermatol. 2011; 147: 1116-1117
        • Foster R.S.
        • Bint L.J.
        • Halbert A.R.
        Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: a pilot study of four patients.
        Australas J Dermatol. 2012; 53: 52-56
        • Mutizwa M.M.
        • Berk D.R.
        • Anadkat M.J.
        Treatment of facial angiofibromas with topical application of oral rapamycin solution (1mgmL(-1)) in two patients with tuberous sclerosis.
        Br J Dermatol. 2011; 165: 922-923
        • Salido R.
        • Garnacho-Saucedo G.
        • Cuevas-Asencio I.
        • et al.
        Sustained clinical effectiveness and favorable safety profile of topical sirolimus for tuberous sclerosis - associated facial angiofibroma.
        J Eur Acad Dermatol Venereol. 2012; 26: 1315-1318
        • Wataya-Kaneda M.
        • Tanaka M.
        • Nakamura A.
        • Matsumoto S.
        • Katayama I.
        A topical combination of rapamycin and tacrolimus for the treatment of angiofibroma due to tuberous sclerosis complex (TSC): a pilot study of nine Japanese patients with TSC of different disease severity.
        Br J Dermatol. 2011; 165: 912-916
        • Haemel A.K.
        • O'Brian A.L.
        • Teng J.M.
        Topical rapamycin: a novel approach to facial angiofibromas in tuberous sclerosis.
        Arch Dermatol. 2010; 146: 715-718
        • Büch Guido
        Entwicklung von Arzneiformen zur dermalen und ophthalmologischen Applikation schwerlöslicher Immunsuppressiva.
        (Dissertation) Freie Universität, Berlin, Germany2007
        • Il’ichev Yuri V.
        • Alquier Lori
        • Maryanoff Cynthia A.
        Degradation of rapamycin and its ring-opened isomer: role of base catalysis.
        ARKTVOC. 2007; : 110-131
        • Junginger H.E.
        • und Bodde H.E.
        Gel structures of dermatological vehicles and their influence on drug release.
        Proc Int Congr Pharm Sci FIP. 1985; 45 (Top. Pharm. Sci.): 329-343
      4. Walther Kern, Theodor Cordes, Untersuchungen über Handelsvaselinen, Article first published online: 23 Sep 2006, http://dx.doi.org/10.1002/ardp.19432810104.

        • Gomes A.A.
        • Gomes Y.V.
        • Lima F.B.
        • Pessoa S.G.
        Multiple facial angiofibromas treated with high-frequency equipment.
        An Bras Dermatol. 2011; 86: S186-S189
        • Weiss E.T.
        • Geronemus R.G.
        New technique using combined pulsed dye laser and fractional resurfacing for treating facial angiofibromas in tuberous sclerosis.
        Lasers Surg Med. 2010; 42: 357-360
        • Boixeda P.
        • Sánchez-Miralles E.
        • Azaña J.M.
        • Arrazola J.M.
        • Moreno R.
        • Ledo A.
        CO2, argon, and pulsed dye laser treatment of angiofibromas.
        J Dermatol Surg Oncol. 1994; 20: 808-812
        • Weinberger C.H.
        • Endrizzi B.
        • Hook K.P.
        • Lee P.K.
        Treatment of angiofibromas of tuberous sclerosis with 5-aminolevulinic acid blue light photodynamic therapy followed by immediate pulsed dye laser.
        Dermatol Surg. 2009; 35: 1849-1851
        • Bae-Harboe Y.S.
        • Geronemus R.G.
        Targeted topical and combination laser surgery for the treatment of angiofibromas.
        Lasers Surg Med. 2013; 45: 555-557
        • Park J.
        • Yun S.K.
        • Cho Y.S.
        • Song K.H.
        • Kim H.U.
        Treatment of angiofibromas in tuberous sclerosis complex: the effect of topical rapamycin and concomitant laser therapy.
        Dermatology. 2014; 228: 37-41