Update on the Systemic Risks of Superpotent Topical Steroids

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