The Position not the Presence of the Halogen in Corticosteroids Influences Potency and Side Effect

Many topical corticosteroids currently on the market contain a halogen substitution at the C6, C9, or the side-chain C21 position of the corticosteroid skeleton. These modifications have enhanced the efficacy of corticosteroids as compared to hydrocortisone as topical anti-inflammatory agents, but have often increased side effects such as skin atrophy, adrenal suppression, and telangiectasia. These side effects have been attributed to the presence of halogens in the corticosteroid molecule and have raised concerns regarding the safety of all halogenated corticosteroids. In this review, we assert that it is the position and nature of the halogen atom(s) in the corticosteroid molecule that determine potency/toxicity, rather than their mere presence. A greater understanding of the role of halogenation in determining corticosteroid potency and side effects will clarify why all halogenated steroids are not the same.