Tuberous Sclerosis Treatment with topical Rapamycin: Beyond treating Facial Angiofibromas

• Tuberous Sclerosis (TSC) is a multisytemic condition characterized by numerous skin signs (shagreen patch, ash leaf macules…). Of these, hypomelanotic macules are the most frequent sign and are present in 90% of patients with TSC. (Macules have to be 3 or more in number to fit in the diagnosis of TSC).

• The cause of TSC is unknown to this day but genetic mutations are present:
  • In TSC type 1 mutation of hamartin is found
  • In TSC2, mutation of tuberin is found

• Topical Rapamycin (Sirolimus), other than treating angiofibromas has been found to be effective in TSC.
  • it has been shown in a study of 6 patients (4 males, 2 females) in the treatment of hypomelanotic macules sun-exposed and non-sunexposed areas.
    • applied in a gel of 0.2% concentration 2 times a day for 12 weeks (this gel passes easily through the skin barrier)
    • satisfactory results (including full repigmentation) were recorded using a chromometer.  Histology shows increased melanin staining and electron microscopy shows and increased number of melanosomes.
  • Pathogenesis* although incompletely understood, it acts  probably by inhibiting mTORC1 and its subsequent signalling pathway. S6K is inhibited and its action on tumor growth and proliferation is suppressed.

Conclusion: topical Rapamycin (Sirolimus) appears to be a therapeutic tool in hypopigmented lesions of TSC

Contributors

Dr Christophe Hsu – dermatologist. Geneva, Switzerland

Source of information: Yang F et al. (Osaka). Plenary session. JSID Annual Meeting (Japanese Society of Investigative Dermatology, 日本研究皮膚科学会) 2014 – Osaka, Japan