Liarozole is a novel inhibitor of the
enzyme cytochrome P450 which has inhibitory effects on the 4-hydroxylation of
retinoic acid. Previous studies have shown that
liarozole is effective in the treatment of
psoriasis. We performed an immunohistochemical study on the lesional skin from 7 patients with extensive plaque
psoriasis, who were treated with systemic
liarozole 75 mg BID for a period of at least 2 months. The effects of
liarozole treatment on clinical and histological parameters were investigated. In particular, the effect of
liarozole on the
integrin markers CD11b and CD18 was studied. For immunohistochemistry, three consecutive biopsies were taken: before treatment, after 4, and after 8 weeks of treatment. Clinical scores and side effects were recorded before and during treatment. The medication was well tolerated and only mild side effects were reported, which were comparable with
hypervitaminosis A. After 2 months of treatment a statistically significant decrease of the extent of body involvement was observed. In the psoriatic plaque, markers for epidermal proliferation and cutaneous
inflammation decreased, and markers for epidermal differentiation increased to values comparable to normal skin. The first
therapeutic effects in the psoriatic plaque occurred after 4 weeks of treatment, and consisted of a decreased induration, accompanied by a decrease of the total number of inflammatory infiltrate cells and a decreased epidermal
ICAM-1 expression. Already after 4 weeks of treatment, a decrease of CD11b-positive cells was observed. Subsequently, after 8 weeks of treatment recruitment of cycling epidermal cells and the number of
involucrin-positive cell layers decreased. The present study demonstrates that
liarozole treatment of
psoriasis results in a reduction of aspects of cutaneous
inflammation and subsequently a reduction of epidermal proliferation and promotion of differentiation. After 4 weeks of treatment, effects are observed on the epidermal
ICAM-1 expression and on the CD11b-positive cell population.