Original article
Long-term treatment of cutaneous manifestations of tuberous sclerosis complex with topical 1% sirolimus cream: A prospective study of 25 patients

https://doi.org/10.1016/j.jaad.2017.04.005Get rights and content

Background

Data on long-term topical sirolimus treatment of the cutaneous manifestations of tuberous sclerosis complex are rare.

Objective

To evaluate the long-term benefit and tolerance of topical 1% sirolimus in tuberous sclerosis complex.

Methods

In this 18-month prospective single-center study, 1% sirolimus cream was applied daily to facial angiofibromas (FAs), fibrous cephalic plaques (FCPs), shagreen patches, hypomelanotic macules, and ungual fibromas. After complete clearance (CC) of FAs, we evaluated a maintenance protocol of 3 applications weekly.

Results

Twenty-five patients were enrolled. Fifty percent obtained CC of FAs within 9 months. Of 7 patients with CC (58%) who were following the maintenance protocol, 6 relapsed within 7 months and 1 was still responding at 1 year. Of 16 patients with FCPs, 7 (44%) remained stable at 12 months and 9 (56%) improved after 3 to 9 months of treatment. Only 1 of 5 patients treated for shagreen patches showed improvement at 12 months. Treatment was well tolerated with no serious adverse events.

Limitations

The small number of patients was a limitation.

Conclusions

Topical 1% sirolimus applied daily produced positive responses in treatment of FAs, FCPs, and facial hypomelanotic macules and was well tolerated. A 3-times-weekly maintenance protocol did not prevent FA relapses.

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

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    Funding sources: None.

    Conflicts of interest: None declared.

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