Effectivity of mTOR inhibition in cutaneous sarcoidosis

Background: Sarcoidosis is an inflammatory condition that can affect various organs and tissue, causing the formation of granulomas and subsequent functional impairment. Cutaneous sarcoidosis lesions can appear as an initial manifestation of the disease or develop later in the clinical course. The origin remains unknown and treatment options are limited. mTOR activation is commonly observed in granulomas of patients across different tissues and induces sarcoidosis-like granulomas in mice. Methods: We conducted a single-center clinical study of persistent glucocorticoid-refractory cutaneous sarcoidosis in a n-of-1 crossover design with the mTOR inhibitor sirolimus as topical and systemic treatment. We included 16 patients of full age presenting persistent, histologically-proven, cutaneous sarcoidosis. Topical treatment. Patients applied 0.1% sirolimus in vaseline, or vaseline only, in a placebo controlled, double-blinded study design. Systemic treatment. The same patients received systemic sirolimus once daily for 4 months. The primary end point was the change in the Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) after topical or systemic treatment. As secondary endpoints we assessed sarcoidosis activity in various affected organs, safety profiles, health-related quality of life and cellular and molecular markers in the skin and peripheral blood. Results: While daily topical treatment did not alter cutaneous lesions, systemic treatment resulted in clinical and histologic remission of skin in 7/10 patients. We identified papular, nodular, plaques, scar and tattoo sarcoidosis as responding morphologies. Improvement of cutaneous lesions appeared long lasting up to 2 years after end of treatment. Systemic treatment showed improvement in additionally affected organs, including sarcoidosis of the lung, eyes and spleen. Conclusion: Short term treatment with sirolimus presents a safe and efficient new treatment option for persistent glucocorticoid-refractory cutaneous sarcoidosis with a long-lasting effect.