Update on the Systemic Risks of Superpotent Topical Steroids

July 2017 | Volume 16 | Issue 7 | Original Article | 643 | Copyright © 2017

Mio Nakamura MD,a Michael Abrouk MD,b Henry Zhu MD,c Benjamin Farahnik MD,d John Koo MD,a and Tina Bhutani MDa

aUniversity of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center, San Francisco, CA bUniversity of California Irvine School of Medicine, Irvine, CA cUniversity of Southern California Keck School of Medicine, Los Angeles, CA dUniversity of Vermont College of Medicine, Burlington, VT

Abstract

INTRODUCTION: The potential for systemic effects due to percutaneous absorption of superpotent topical steroids has been a longstanding concern. The Food and Drug Administration currently recommends limiting the use of superpotent topical steroids to 50g per week for 2 or 4 consecutive weeks depending on the formulation, which is mostly based on the exact duration with which phase 3 clinical trials were allowed to be conducted per the FDA. This article reviews all published clinical incidence of adrenal adverse effects in the medical literature, specifically Cushing’s syndrome (CS) and pathologic adrenal suppression (PAAS), to try to ascertain a more realistic limit for the safe use of superpotent topical steroids as it pertains to its potential systemic effects.

METHODS: Literature search was conducted using PubMed. Only cases of CS and PAAS secondary to the use of Class I superpotent topical steroids were included. Pediatric cases and full articles unavailable in English were excluded.

RESULTS: There were a total of 14 cases of CS and 5 cases of subsequent PAAS found in the current literature.

DISCUSSION: From our review of these cases, if the amount used per week is within FDA guidelines, it appears that patients needed to use superpotent topical steroids for far greater than 2 or 4 weeks to develop CS or PAAS. CS did not necessarily predict occurrence of PAAS, but in all cases CS appeared to be a prerequisite for developing PAAS. All cases of CS and all but one case of PAAS were reversible. If excessive amount of greater than 50g per week is avoided, it appears that superpotent topical steroids may be safe to use consecutively for months, perhaps even years, without causing systemic effects.

J Drugs Dermatol. 2017;16(7):643-648.

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INTRODUCTION

For many years, topical corticosteroids have remained a mainstay therapy for various inflammatory dermatologic conditions. Since their introduction, the potential for systemic effects caused by percutaneous absorption of the steroid has been a longstanding concern. Systemic absorption of large amounts of steroid can cause Cushing’s syndrome (CS) or exogenous hypercortisolism, which presents as central obesity, facial plethora, skin atrophy, striae formation, proximal muscle atrophy, weakness, glucose intolerance, hypertension, osteoporosis, and psychological changes.1 Suppression of the adrenal gland can occur, which is an appropriate physiologic response to exogenous cortisol due to the negative feedback loop of the hypothalamus-pituitary-adrenal axis (HPA-axis). However, suppression of the HPA-axis becomes clinically detrimental if the patient becomes symptomatic after discontinuing use of the exogenous steroid due to inability of the adrenal gland to promptly supply hormones. This can lead to adrenal insufficiency and even adrenal crisis.This is termed pathologic adrenal suppression (PAAS) in contrast to physiologic adrenal suppression (PHAS),2 and this state of hypocortisolism can manifest as hypotension, hypoglycemia, electrolyte abnormalities, weakness, and even death.3 Due to these concerns, the Food and Drug Administration (FDA) has limited the use of superpotent topical steroids in adults to up to 50g per week for durations of 4 weeks for clobetasol propionate 0.05% spray and 2 weeks for all other formulations. These warnings exist because phase 3 clinical trials conducted for FDA approval of superpotent topical steroids were of only 2 to 4 week duration due to FDA mandated restrictions. Of note, during this time period there were no reports of CS or PAAS.4-10 Another non-pivotal (ie, not for FDA approval) clinical trial by Carruthers et al (1975) evaluated the use of clobetasol propionate 0.05% cream for a duration of 10 weeks to 18 months and reported CS and subsequent adrenal insufficiency upon discontinuation of therapy only in subjects who used greater than 100g per week,11 which is double the current allowable limit of 50g per week per the FDA. However, specific symptoms of adrenal suppression were not described; therefore, the details regarding these cases are unclear. The FDA warnings with regard to CS and adrenal suppression have deterred many practicing physicians from using superpotent topical steroids outside of the scope of the FDA recommended guidelines. However, these guidelines may

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