The occurrence of untoward physiological effects after systemic administration of cortisone and hydrocortisone provided a stimulus for investigators to develop hydrocortisone lotions and ointments for topical application. By applying hydrocortisone topically, the anti-inflammatory effects could be utilized without the risk of sodium and water retention, edema, and other undesirable physiological changes associated with systemic administration. In the three years since the introduction of hydrocortisone products for topical application, occurrence of systemic absorption after topical application has not been reported. During the past 15 months since we began evaluating the therapeutic effects of topically applied hydrocortisone in various concentrations and vehicles, we have become suspicious of possible systemic absorption of topically applied hydrocortisone. For example, in using the simultaneous paired comparison method, it was often noted that the area receiving the placebo lotion or ointment appeared to respond almost equally to the area receiving hydrocortisone. Also, it was observed in a
Fitzpatrick TB, Griswold HC, Hicks JH. SODIUM RETENTION AND EDEMA FROM PERCUTANEOUS ABSORPTION OF FLUDROCORTISONE ACETATE. JAMA. 1955;158(13):1149–1152. doi:10.1001/jama.1955.02960130003002
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