Topical rapamycin for angiofibromas in patients with tuberous sclerosis: how does it work in clinical practice?

Abstract

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.

Keywords

Tuberous sclerosis / topical rapamycin / angiofibroma / clinical practice

References

[1] Osborne JP,Webb D.Epidemiology of tuberous sclerosis..Ann N Y Acad Sci1991;615:125-7

[2] Krueger DA.Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference.Pediatr Neurol2013;49:255-65

[3] Curatolo P,Jozwiak S.Tuberous sclerosis..Lancet2008;372:657-68

[4] Hofbauer GF,Corsenca A,French LE,Serra AL.The mTOR inhibitor rapamycin significantly improves facial angiofibroma lesions in a patient with tuberous sclerosis..Br J Dermatol2008;159:473-5

[5] Haemel AK,Teng JM.Topical rapamycin: a novel approach to facial angiofibromas in tuberous sclerosis..Arch Dermatol2010;146:715-8

[6] Mutizwa MM,Anadkat MJ.Treatment of facial angiofibromas with topical application of oral rapamycin solution (1mgmL(-1)) in two patients with tuberous sclerosis..Br J Dermatol2011;165:922-3

[7] DeKlotz CM,Singh S,MacGregor JL.Dramatic improvement of facial angiofibromas in tuberous sclerosis with topical rapamycin: optimizing a treatment protocol..Arch Dermatol2011;147:1116-7

[8] Truchuelo T,Rios L,Jaen P.Facial angiofibromas treated with topical rapamycin: an excellent choice with fast response..Dermatol Online J2012;18:15

[9] Kaufman McNamara E,Fleischer ABJr.Successful treatment of angiofibromata of tuberous sclerosis complex with rapamycin..J Dermatolog Treat2012;23:46-8

[10] Knopfel N,Bauza A.Topical 0.2% rapamycin to treat facial angiofibromas and hypomelanotic macules in tuberous sclerosis..Actas Dermosifiliogr2014;105:802-3

[11] Wataya-Kaneda M,Nakamura A,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 Dermatol2011;165:912-6

[12] Foster RS,Halbert AR.Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: a pilot study of four patients..Australas J Dermatol2012;53:52-6

[13] Salido R,Cuevas-Asencio I,Galán-Gutierrez M,Moreno-Giménez JC.Sustained clinical effectiveness and favorable safety profile of topical sirolimus for tuberous sclerosis - associated facial angiofibroma..J Eur Acad Dermatol Venereol2012;26:1315-8

[14] Tanaka M,Nakamura A,Katayama I.First left-right comparative study of topical rapamycin vs. vehicle for facial angiofibromas in patients with tuberous sclerosis complex..Br J Dermatol2013;169:1314-8

[15] Park J,Cho YS,Kim HU.Treatment of angiofibromas in tuberous sclerosis complex: the effect of topical rapamycin and concomitant laser therapy..Dermatology2014;228:37-41

[16] Tu J,Bint LJ.Topical rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: follow up of a pilot study and promising future directions..Australas J Dermatol2014;55:63-9

[17] Koenig MK,Roberson J,Slopis J,Northrup H.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..Drug R D2012;12:121-6 PMCID:PMC3585992

[18] Vasani RJ.Facial angiofibromas of tuberous sclerosis treated with topical sirolimus in an Indian patient..Indian J Dermatol2015;60:165-9 PMCID:PMC4372909

[19] Pynn EV,Hunasehally PR.Successful topical rapamycin treatment for facial angiofibromata in two children..Pediatr Dermatol2015;32:e120-3

[20] Knoll GA,Mallick R,Buenaventura CD,Barsoum R,Blydt-Hansen TD,Felipe CR,Gallon L,Glotz D,Guba M,Salgo R,Tedesco-Silva H,Watson C.Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data..BMJ2014;349:g6679 PMCID:PMC4241732

[21] Salido-Vallejo R,Garnacho-Saucedo G,Llorca D,Moreno-Giménez JC.Facial Angiofibroma Severity Index (FASI): reliability assessment of a new tool developed to measure severity and responsiveness to therapy in tuberous sclerosis-associated facial angiofibroma..Clin Exp Dermatol2014;39:888-93