Topical sirolimus for the treatment of facial angiofibromas in tuberous sclerosis patient: a case report


  • Ankit Bhardwaj Department of Pharmacology, University College of Medical Science, Dilshad Garden, Delhi, India
  • Mukesh Manjhi Department of Dermatology and Venerology, Hamdard Institute of Medical Sciences and Research, New Delhi, India



Tuberous sclerosis complex, Angiofibroma, mTOR inhibitors, Sirolimus


Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disorder seen in 1/6000 births. Facial angiofibroma is the most common cosmetic disfiguring cutaneous manifestation of it. Therapeutic modalities include cryotherapy, podophyllotoxin application, electrocoagulation, surgery and laser therapy associated with their own high risk of complications and sequelae. Sirolimus is a lipophilic lactone isolated from Streptomyces hygroscopicus (soil bacteria), found to have anti-T-cell properties and classifies as an anticancer drug from the mammalian target of rapamycin (mTOR) inhibitors. Sirolimus binds with mTOR and causes inhibition of mTOR activity and VEGF‑stimulated endothelial cell proliferation. Topical preparation produced by crushing tablets of sirolimus 1 mcg and mixing in an aqueous base emollient or the solution form of sirolimus has been used with beneficial effects in the treatment of angiofibroma, especially in younger patients. Here we reported a case of a 34-year-old male, a known case of TSC with facial angiofibroma in which the topical 0.1% sirolimus had been used with beneficial effects and clinical outcomes.



Chopra M, Lawson JA, Wilson M, Kennedy SE, Taylor P, Buckley MF, et al. An Australian tuberous sclerosis COHORT: are surveillance guidelines being met? J Paediatr Child Health. 2011;47(10):711-6.

Wheless JW, Almoazen H. A novel topical rapamycin cream for the treatment of facial angiofibromas in tuberous sclerosis complex. J Child Neurol. 2013;28(7):933-6.

National Organization for Rare Disorders (NORD). Fact sheet: Tuberous sclerosis. Available at: Accessed on 14 May 2022.

Schwartz RA, Fernández G, Kotulska K, Jóźwiak S. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007;57(2):189-202.

Webb DW, Clarke A, Fryer A, Osborne JP. The cutaneous features of tuberous sclerosis: a population study. Br J Dermatol. 1996;135(1):1-5.

Salido R, Garnacho-Saucedo G, Cuevas-Asencio I, Ruano J, Galán-Gutierrez M, Vélez A, et al. Sustained clinical effectiveness and favorable safety profile of topical sirolimus for tuberous sclerosis – Associated facial angiofibroma. J EurAcad Dermatol Venereol. 2012;26(10):1315-8.

Paghdal KV, Schwartz RA. Sirolimus (rapamycin): From thesoil of Easter Island to a bright future. J Am Acad Dermatol. 2007;57(6):1046-50.

Ng KH, Ng SM, Parker A. Annual review of children with tuberous sclerosis. Arch Dis Child Educ Pract Ed. 2015;100(3):114-21.

Tonekaboni SH, Tonekaboni SH, Tousi P, Ebrahimi A, Ahmadabadi F, Keyhanidoust Z, et al. Clinical and para clinical manifestations of tuberous sclerosis: a cross sectional study on 81 pediatric patients. Iran J Child Neurol. 2012;6(3):25-31.

Krueger DA, Northrup H; International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex surveillance and management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49(4):255-65.

Birca A, Mercier C, Major P. Rapamycin as an alternative to surgical treatment of subependymal giant cell astrocytomas in a patient with tuberous sclerosis complex. J Neurosurg Pediatr. 2010;6(4):381‑4.

Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, et al. Everolimus for subependymal giant‑cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010;363(19):1801‑11.

Li S, Takeuchi F, Wang JA, Fan Q, Komurasaki T, Billings EM, et al. Mesenchymal‑epithelial interactions involving epiregulin in tuberous sclerosis complex hamaratomas. Proc Natl Acad Sci U S A. 2008;105(9):3539‑44.

Hofbauer GF, Marcollo‑Pini A, Corsenca A, Kistler AD, French LE, Wüthrich RP, et al. The mTOR inhibitor rapamycin significantly improves facial angiofibroma lesions in a patient with tuberous sclerosis. Br J Dermatol. 2008;159(2):473‑5.

Haemel, AK, O’Brian AL, Teng JM. Topical rapamycin: a novel approach to facial angiofibromas in tuberous sclerosis. Arch Dermatol. 2010;146(7):715‑8.

Koenig M, Hebert A, Roberson J, Samuels J, Slopis J, Woerner A, et al. Topical rapamycin therapy to alleviate the cutaneous manifestation of tuberous sclerosis complex-a double blind, randomised, controlled trial to evaluate safety and efficacy of topically applied rapamycin. Drugs R D. 2012:12(3):123‑6.