Journal of Investigative Dermatology 2015-07-01

Topical Mineralocorticoid Receptor Blockade Limits Glucocorticoid-Induced Epidermal Atrophy in Human Skin.

Eve Maubec, Cédric Laouénan, Lydia Deschamps, Van Tuan Nguyen, Isabelle Scheer-Senyarich, Anne-Catherine Wackenheim-Jacobs, Maud Steff, Stéphanie Duhamel, Sarah Tubiana, Nesrine Brahimi, Stéphanie Leclerc-Mercier, Béatrice Crickx, Claudine Perret, Selim Aractingi, Brigitte Escoubet, Xavier Duval, Philippe Arnaud, Frederic Jaisser, France Mentré, Nicolette Farman

Index: J. Invest. Dermatol. 135 , 1781-9, (2015)

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Abstract

A major deleterious side effect of glucocorticoids is skin atrophy. Glucocorticoids activate the glucocorticoid and the mineralocorticoid (MR) receptor, both present in the epidermis. We hypothesized that glucocorticoid-induced epidermal atrophy may be related to inappropriate occupancy of MR by glucocorticoids. We evaluated whether epidermal atrophy induced by the topical glucocorticoid clobetasol could be limited by coadministration of MR antagonist. In cultured human skin explants, the epidermal atrophy induced by clobetasol was significantly limited by MR antagonism (canrenoate and eplerenone). Blockade of the epithelial sodium channel ENaC by phenamil was also efficient, identifying a role of MR-ENaC cascade in keratinocytes, acting through restoration of clobetasol-induced impairment of keratinocyte proliferation. In the SPIREPI randomized double-blind controlled trial, gels containing clobetasol, the MR antagonist spironolactone, both agents, or placebo were applied on four zones of the forearms of 23 healthy volunteers for 28 days. Primary outcome was histological thickness of the epidermis with clobetasol alone or clobetasol+spironolactone. Spironolactone alone did not affect the epidermal thickness but coapplication of clobetasol and spironolactone significantly limited clobetasol-induced atrophy and was well tolerated. Altogether, these findings identify MR as a factor regulating epidermal homeostasis and suggest that topical MR blockade could limit glucocorticoid-induced epidermal atrophy.