Effects of Systemic Treatment with Liarozole on Cutaneous Inflammation, Epidermal Proliferation and Differentiation in Extensive Plaque Psoriasis

Abstract

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 the 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.

New Dermatological Agents for the Treatment of Psoriasis

“…For example, there is a decrease in the CD 11b-positive cell population (neutrophils, monocytes, and macrophages) and a decrease in epidermal ICAM-1 expression. 125 The side effects of liarozole include those of hypervitaminosis A. 125 Recently, more potent inhibitors in this class have been identified, such as R 115866.…”

“…125 The side effects of liarozole include those of hypervitaminosis A. 125 Recently, more potent inhibitors in this class have been identified, such as R 115866. 126 It remains to be determined whether a topical CYP26 inhibitor will be effective in the treatment of psoriasis.…”

Cell-Kinetic Evidence for Increased Recruitment of Cycling Epidermal Cells in Psoriasis: The Ratio of Histone and Ki-67 Antigen Expression Is Constant

“…The reproducibility and sensitivity using the MIB-1 antibody instead of the Ki-67 antibody is better, because of a reduction of non-specific cytoplasm staining. In addition, another indication of the reliability and usefulness of the Ki-67/MIB-1 antibodies as proliferation markers is their potential to reveal the reduction of Ki-67 expression following antipsoriatic treatments [12, 16, 19, 20, 21, 23, 24, 25, 26, 27]. However, the large interstudy variability makes the comparison of absolute counts difficult.…”

Antimycotics: Why Are They Effective in the Treatment of Seborrheic Dermatitis?

“…KET is a general inhibitor of P450 enzymes, of which some are necessary for the metabolism of steroid hormones including vitamin D compounds or for androgen biosynthesis. Consequently, it has been shown that imidazole-like compounds including liarozole that have been demonstrated to exert inhibitory effects on the 4-hydroxylation of retinoic acid (RA) and/or on the 1,25-dihydroxyvitamin D/24-hydroxylase are effective in the topical or systemic treatment of inflammatory skin diseases including psoriasis [16][17][18]. Liarozole is an imidazole-like compound that inhibits the RA 4-hydroxylasemediated breakdown of all-trans-RA, causing elevation of plasma and cutaneous levels of RA.…”

“…Liarozole is an imidazole-like compound that inhibits the RA 4-hydroxylasemediated breakdown of all-trans-RA, causing elevation of plasma and cutaneous levels of RA. Thus liarozole acts as a retinoid-mimetic drug and consequently has been found to be effective in the treatment of retinoid-responsive conditions such as chronic plaque psoriasis and ichthyoses [16][17][18].…”