“…On the basis of the studies on intra dermal metabolism of corticoids, it has been established for human skin that this type of esterolytic reaction occurs in the skin [Pannatier et al, 1978;Cheung et al, 1985;Tauber and Rost, 1987], Alongside enzymatic ester hydrolysis, nonenzymatic conversions, especially of C l7 monoesters, can apparently also take place in the epidermis [Bundgaard and Hansen, 1981;Yip et al, 1983]. In contrast to this, halogen substituents, most often in position Cftalpha and Gjalpha, increase the affinity of the gluco corticoid molecule to the intracellular recep tor protein and thus lead to an increase in the intrinsic activity of the steroid on the one hand; on the other hand halogen substituents cause a delay of the systemic metabolism [Myles et al, 1957;Wolff, 1979]. By means of highly potent, sometimes multiple-halogenated glucocorticoids, strong local effects can often be caused even with only small amounts of substance penetrating the deeper layers of the skin; this holds also true, however, of the amount of substance reaching the systemic circulation, which invalidates one of the es sential arguments for a purely locally oriented form of therapy.…”