THE EFFECTS OF ORAL LIAROZOLE ON EPIDERMAL PROLIFERATION AND DIFFERENTIATION IN SEVERE PLAQUE PSORIASIS ARE COMPARABLE WITH THOSE OF ACITRETIN

The imidazole derivative liarozole is a potent inhibitor of cytochrome P450-dependent 4-hydroxylation of endogenous all-trans retinoic acid, thereby increasing the levels of all-trans retinoic acid in both plas ma and skin. As part of a large, double-blind, randomized clinical stu dy, we investigated the cell biological alterations in uninvolved and lesional skin of 20 patients with severe plaque psoriasis, who were tr eated with either liarozole or acitretin. The extent and severity of t he skin lesions, as recorded by the Psoriasis Area and Severity index score, was significantly reduced (P less than or equal to 0.05) after 12 weeks of treatment in both the acitretin-and the liarozole-treated group. A significant decrease in the markers for inflammation (neutrop hils), epidermal proliferation (Ki-67-positive cells), normal differen tiation (transglutaminase) and abnormal differentiation [cytokeratin 1 6 and skin-derived antileucoproteinase (SKALP), also known as elafin] was seen in both groups. No significant differences were noted in clin ical scores or cell biological scores between the liarozole- and acitr etin-treated group, None of the markers returned to the levels seen in uninvolved skin or in normal human skin. The expression of epidermal fatty acid binding protein (E-FABP) was only minimally decreased after 12 weeks of treatment, a substantial part of the stratum spinosum rem aining positive. SKALP levels in serum fell in both groups with simila r kinetics and showed a statistically significant correlation with cli nical scores, A remarkable finding in the uninvolved skin of patients treated with liarozole or acitretin was the distinct focal expression of SKALP in the granular layer and the expression of E-FABP in the spi nous layers, which is not found in normal human skin. Although the mec hanism of action differs fundamentally, liarozole and acitretin show s imilar effects with respect to clinical effects and cell biological ch anges in the lesional and nonlesional skin.