Spironolactone affects steroid skin damage

April 22, 2015

It might seem unlikely, but researchers have found the antihypertensive drug spironolactone reduces skin atrophy from topical corticosteroid use.

It might seem unlikely, but researchers have found the antihypertensive drug spironolactone reduces skin atrophy from topical corticosteroid use.  

In a study published online February in the Journal of Investigative Dermatology, researchers from Inserm report on their hypothesis that skin atrophy, which results from corticosteroid-based dermatological creams, might be related to these topicals’ activation of mineralocorticoid receptors in the epidermis.

“These receptors, which are present in the kidney, heart, eye, and certain neurons in particular, reacted with aldosterone, a hormone that regulates the blood pressure. Moreover, previous studies also showed them to be highly sensitive to corticosteroids,” according to a release.

They found that corticosteroid application to cultured skin results in skin thinning. In six days, the epidermis’s thickness was reduced by one-third. To remedy the side effect, researchers induced a pharmacological receptor blockade by adding an antagonist to corticosteroid treatment. Spironolactone is a mineralocorticoid receptor antagonist.

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They tested a spironolactone-based treatment for 28 days in 23 healthy volunteers, applying creams of different compositions to four areas of the volunteers’ arms. The researchers applied a cream containing a corticosteroid used in dermatology; a cream containing spironolactone; a combination of both drugs; and a placebo. They found that by adding spironolactone to the corticosteroid, they significantly limited skin atrophy.

Inserm Research Director Nicolette Farman, M.D., Ph.D., writes in an email to Dermatology Times that, if the drug is eventually approved for topical use (because oral absorption is not efficient for this reason), dermatologists might use spironolactone topically in patients with skin diseases requiring short-term glucocorticoid application, as in some patients with eczema or psoriasis.

“We did not see any side effects after one month treatment of healthy volunteers; however, there is a need for extensive toxicity (local at the level of the skin surface, and, general, because of possibility of percutaneous absorption) in normal and diseased skin,” Dr. Farman writes. “The use of topical spironolactone to limit glucocorticoid-induced skin atrophy is not approved yet for dermatologists. We provided a proof of concept of efficacy, but much is still required before human use. It is necessary to reformulate spironolactone for topical use, to do toxicology assessments, and to perform clinical evaluation in patients with skin diseases. We have deposited a patent application, and we are now exploring the possibilities to progress towards future use of this kind of drug for patients.”

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References: Maubec E, Laouénan C, Deschamps L, et al. Topical Mineralocorticoid Receptor Blockade Limits Glucocorticoid-Induced Epidermal Atrophy in human Skin. J Invest Dermatol. 2015; [Epub ahead of print]

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