Original articleLong-term treatment of cutaneous manifestations of tuberous sclerosis complex with topical 1% sirolimus cream: A prospective study of 25 patients
Section snippets
Study design
From June 2015 to December 2016, we prospectively included all patients who requested and received topical sirolimus treatment for TSC skin manifestations at the Regional Center of Competence of Tuberous Sclerosis Complex of the University Hospital of Montpellier. Our local ethics committee approved the study protocol (IRB 15/06.06, dated June 9, 2015).
Inclusion criteria
Eligible patients were consecutively included if they had a diagnosis of TSC based on validated criteria5 from the 2012 International Tuberous
Patient characteristics
Twenty-eight patients met the criteria for enrollment, but 3 were excluded because they missed the first 2 compulsory follow-up visits (2 patients) or showed poor compliance (1 patient) (Fig 1). Pertinent characteristics of the 25 patients are summarized in Supplemental Table II (available at http://www.jaad.org). The median age was 14 years (range 4-47), including 17 children younger than 18 years; 16 (64%) were female and 9 were male (36%). Autism and intellectual disability were noted in 20%
Discussion
This study confirmed that once-daily application of 1% sirolimus cream can be a useful and well-tolerated long-term treatment for the FAs of TSC. We limited sirolimus application to once per day in the evening to encourage better compliance, which is similar to the usual practice in topical acne treatment,33, 34 because it appears that topical sirolimus efficacy is dependent on regular, long-term application. We also wanted to facilitate application of sunscreen to the face in the morning, as
References (38)
- et al.
International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference
Pediatr Neurol
(2013) - et al.
Topical rapamycin solution to treat multiple facial angiofibromas in a patient with tuberous sclerosis
Actas Dermo-Sifiliográficas
(2012) - et al.
Topical use of mammalian target of rapamycin (mTOR) inhibitors in tuberous sclerosis complex—a comprehensive review of the literature
Pediatr Neurol
(2016) - et al.
Topical 0.2% rapamycin to treat facial angiofibromas and hypomelanotic macules in tuberous sclerosis
Actas Dermo-Sifiliográficas
(2014) - et al.
Improvement of tuberous sclerosis complex (TSC) skin tumors during long-term treatment with oral sirolimus
J Am Acad Dermatol
(2015) - et al.
A randomized controlled pilot study of strategies to increase adherence in teenagers with acne vulgaris
J Am Acad Dermatol
(2011) - et al.
Acne in recipients of renal transplantation treated with sirolimus: clinical, microbiologic, histologic, therapeutic, and pathogenic aspects
J Am Acad Dermatol
(2006) Identification and characterization of the tuberous sclerosis gene on chromosome 16
Cell
(1993)- et al.
Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34
Science
(1997) - et al.
Loss of heterozygosity in tuberous sclerosis hamartomas
J Med Genet
(1996)
Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance
Int J Dermatol
Effect of angiofibromas on quality of life and access to care in tuberous sclerosis patients and their caregivers
Pediatr Dermatol
First left-right comparative study of topical rapamycin vs. vehicle for facial angiofibromas in patients with tuberous sclerosis complex
Br J Dermatol
A novel topical rapamycin cream for the treatment of facial angiofibromas in tuberous sclerosis complex
J Child Neurol
Successful treatment of angiofibromata of tuberous sclerosis complex with rapamycin
J Dermatol Treat
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 RD
Facial angiofibromas treated with topical rapamycin: an excellent choice with fast response
Dermatol Online J
A novel application of topical rapamycin formulation, an inhibitor of mTOR, for patients with hypomelanotic macules in tuberous sclerosis complex
Arch Dermatol
Dramatic improvement of facial angiofibromas in tuberous sclerosis with topical rapamycin: optimizing a treatment protocol
Arch Dermatol
Cited by (46)
Use of mTOR inhibitors (rapalogs) for the treatment of skin changes in tuberous sclerosis complex
2022, Archives de PediatrieCitation Excerpt :Wataya-Kaneda and colleagues, by far the most prolific authors in this topic, do not use it but another score combining AF size reduction and lessening of redness instead [17]. Anyway, to our knowledge, 4 controlled trials have been published between 2015 and 2020 [15,22,23,25], in addition to 7 large prospective, open-label or retrospective series [17–21,24]. The Table 1 summarizes the design and main findings for the trials found in the literature from 2015 onward.
Validation of the Index for Facial Angiofibromas: A new scoring tool to assess facial angiofibromas in the tuberous sclerosis complex
2022, Journal of the American Academy of DermatologyChemoprevention of cutaneous squamous cell carcinoma and its precursors in solid organ transplant recipients using topical sirolimus: A randomized, double-blind, placebo-controlled pilot trial
2022, Journal of the American Academy of DermatologyUpdated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations
2021, Pediatric NeurologyCitation Excerpt :Skin lesions that are smaller and flatter appear to respond better to topical sirolimus than bulky lesions, so early treatment is recommended. Long-term therapy will likely be required to maintain benefit.153,154 Adverse effects of topical sirolimus are generally mild, such as application-site skin irritation, dry skin, or acne.154
Long-Term Effects of Sirolimus on Human Skin TSC2-Null Fibroblast‒Like Cells
2021, Journal of Investigative DermatologyCitation Excerpt :These cells (Darling et al., 2010) were used to study the effect of sirolimus, estrogen, and chloroquine on cell proliferation and size. It has been reported previously that there is an increase in AML tumor size and also in the size of skin lesions after withdrawal of sirolimus (Bissler et al., 2008; Darling, 2018; Malissen et al., 2017). To obtain further insight into the cellular and molecular aspects of sirolimus treatment and withdrawal, we studied the effects of sirolimus on the proliferation of TSC2−/− skin tumor fibroblasts.
Phakomatoses
2019, Dermatologic ClinicsCitation Excerpt :Ungal fibromas are especially known to recur.205 Topical mTOR inhibitors have shown benefit for angiofibroma, fibrous plaques, and hypomelanotic macules.213,236,272–274 A twin study even showed a possible prophylactic benefit to mTOR inhibitors in preventing angiofibroma formation,275 which may counter the current guidance to only treat fibromas after adolescence.214
Funding sources: None.
Conflicts of interest: None declared.