Is sirolimus effective to sarcoidosis?
December 16, 2020 / Cutting edges
Sarcoidosis is a multi-systemic noncaseous granulomatous disease of unknown etiology. It is a designated intractable disease with the prevalence at 8-10 per 100,000 population in Japan. Corticosteroid medication is the standard therapy, but it is problematic that tapering is hard in some patients with severe disease. Moreover, lung fibrosis is progressive in some patients with long-term follow-up. Recent studies on an animal model and exome analysis of familial cases demonstrated a role of activated mTOR signaling in the pathogenesis of sarcoidosis. Sirolimus forms a complex with FK-binding protein-12 that binds to and inhibit mTOR activity. Consistently, in actual clinical reports, sirolimus improved lung involvements radiographically and reduced laryngeal granulomas. A clinical trial of sirolimus to cutaneous sarcoidosis is on going by Medical University of Vienna.
References
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Exome sequencing and pathogenicity-network analysis of 5 French families implicate mTOR signalling and autophagy in familial sarcoidosis
Alain Calender, Clarice X. Lim, Thomas Weichhart, Adrien Buisson, Valérie Besnard, Pierre Antoine Rollat-Farnier, Claire Bardel, Pascal Roy, Vincent Cottin, Gilles Devouassoux, Amélie Finat, Stéphane Pinson, Serge Lebecque, Hilario Nunes, Dominique Israel-Biet, Abderazzaq Bentaher, Dominique Valeyre, Yves Pacheco in the frame of GSF (Group Sarcoidosis France)
European Respiratory Journal 2019; DOI: 10.1183/13993003.00430-2019 -
Successful Response to Treatment with Sirolimus in Pulmonary Sarcoidosis
Nishant Gupta, Jack H Bleesing, Francis X McCormack Am J Respir Crit Care Med
. 2020 Nov 1;202(9):e119-e120.doi: 10.1164/rccm.202004-0914IM. -
Treatment-recalcitrant laryngeal sarcoidosis responsive to sirolimus
Karen J Kelleher, John Russell, Orla G Killeen, Timothy Ronan Leahy
BMJ Case Rep. 2020 Aug 26;13(8):e235372. doi: 10.1136/bcr-2020-235372.