RETINOIDS IN PSORIASIS AND DISORDERS OF KERATINIZATION

Synthetic retinoids, particularly the aromatic retinoid etretinate (Tigason, Europe; Tegison, United States), have had an established role in the treatment of psoriasis and a variety of ichthyosiform disorders for more than a decade. Isotretinoin (Accutane), which was released at approximately the same time, plays a less important role in these disorders. The mechanism of action of etretinate is still incompletely understood although, like retinoic acid, it is thought to interfere with the terminal differentiation of keratinocytes. The recent detection of nuclear retinoic acid receptors may lead to a unifying theory of retinoid effects and provide the means for more targeted use of this class of compounds. The substantial amount of data on the clinical effectiveness of etretinate was obtained empirically from numerous multicenter trials and individual reports; its indications, dosimetry, pharmacokinetics, and side effects are well established. The main adverse effect associated with etretinate is its teratogenicity (common to all retinoids), which is of particular concern because the lipophilic compound is stored in fat tissue, resulting in an elimination half-life of as many as 120 days. To avoid this problem the much less lipophilic unesterified acid of etretinate, acitretin, has been made available and has now replaced etretinate in many countries. Acitretin represents the active principle of etretinate and has an elimination half-life of 2 days. No significant clinical differences have been observed between these two compounds. Partial in vivo conversion of acitretin into etretinate, however, has been described in some patients. Both compounds are standard treatment for pustular and erythrodermic psoriasis. Plaque-type psoriasis responds less well and generally requires additional therapeutic measures to achieve complete clearing. Maintenance therapy for a few months after clearing results in a significantly decreased relapse rate. The severe plaque-type psoriasis (> 15% of body surface) should be treated with synthetic retinoids. Most types of ichthyoses, Darier's disease, some types of palmoplantar keratoderma, and pityriasis rubra pilaris are responsive to etretinate and acitretin. However, only severe manifestations of hereditary disorders of keratinization should be treated with retinoids because maintenance of therapeutic effects is possible only with continued administration of the drug.