What are the dermatological uses of sirolimus (Rapamune)?

From the Guidelines

Sirolimus has a specific use in dermatology, particularly in the prevention of cutaneous squamous cell carcinoma (cSCC) in organ transplant recipients, by converting from calcineurin inhibitors to mTOR inhibitors like sirolimus, which has been shown to reduce the risk of post-transplant skin cancer. This is based on the study by Blomberg et al. 1, which suggests that sirolimus may have a beneficial effect in preventing subsequent cSCC after the first post-transplant cSCC, although its use is limited by a relatively high rate of discontinuation due to side effects. The study found that low-dose sirolimus trials persisted in reducing the risk of keratinocyte carcinoma (HR 0.43,95% CI 0.24–0.78), while the risk of death was no longer statistically significant (HR 1.07,95% CI 0.81–1.41).

Some key points to consider when using sirolimus in dermatology include:

• Sirolimus has immunosuppressive and anticarcinogenic effects, making it a potential alternative to traditional immunosuppressant drugs 1
• The medication works by inhibiting the mammalian target of rapamycin (mTOR) pathway, which regulates cell growth and proliferation 1
• Common side effects of sirolimus include mild irritation, redness, or burning at the application site, though these are typically less severe than with systemic administration 1
• Sirolimus may be used in combination with other systemic agents, such as ciclosporin, to treat certain skin conditions like psoriasis and psoriatic arthritis, although this requires careful monitoring due to increased immunosuppression 1

In terms of specific dosing and administration, sirolimus may be considered for highly selected patients, such as those with aggressive cSCC disease, where benefits outnumber disadvantages. However, the optimal dosing and administration of sirolimus in dermatology require further study, particularly to determine the specific threshold at which prevention of skin cancer is balanced with minimization of adverse events 1.

From the Research

Uses of Sirolimus in Dermatology

Sirolimus has several uses in dermatology, including:

• Treatment of facial angiofibromas in tuberous sclerosis complex (TSC) 2, 3
• Treatment of psoriasis, particularly when used in combination with a subtherapeutic dose of cyclosporin 4
• Treatment of port-wine stains, with evidence of effectiveness for combined sirolimus and pulsed-dye laser 3
• Treatment of cutaneous vascular abnormalities, such as Kaposi's sarcoma 2, 5
• Treatment of other inflammatory and malignant disorders of the skin, such as angiofibromas and skin tumors 2, 5

Forms of Sirolimus Used in Dermatology

Sirolimus can be administered in various forms, including:

• Oral systemic therapy, with dosing regimens varying depending on the condition being treated 2
• Topical therapy, with concentrations ranging from 0.1% to 1% and formulations including creams, ointments, and gels 2, 3

Efficacy and Safety of Sirolimus in Dermatology

The efficacy and safety of sirolimus in dermatology have been demonstrated in several studies, with:

• Level 1 evidence for the efficacy of sirolimus in conditions such as TSC and GVHD prophylaxis 2
• Generally favorable outcomes and good tolerability in other indications, although data quality is mixed 3
• Common side effects including mucositis, cytopenias, lipid abnormalities, and nausea/vomiting with oral systemic therapy 2
• Common side effects including skin irritation and pruritus with topical therapy 3