Topical glucocorticoids with improved benefit/risk ratio: do they exist?

Topical glucocorticoids are still among the dermatologicals most frequently used. This is due to their undebatable potency in inflammatory skin disease. Their use is limited by the fear of side effects both systemic and topical, especially skin atrophy. Hence, congeners with an increased benefit-risk ratio are urgently needed and research on new drugs no longer focuses on more active drugs but safer ones. Only recently, evidence has been forwarded that the goal is realistic. Some new glucocorticoids, especially the nonfluorinated double-ester type such as prednicarbate, appear promising. In fact, they seem to affect fibroblast growth in vitro as well as skin thickness in vivo less than equipotent conventional glucocorticoids. Pertinent findings in humans have been obtained with the use of ultrasound equipment. The relevant aspects of chemistry, pharmacology, clinical benefits, and toxicology of the various glucocorticoids old and new are reviewed, as are potential future alternatives.