Effects of systemic treatment with liarozole on cutaneous inflammation, epidermal proliferation and differentiation in extensive plaque psoriasis. 1998

J P van Pelt, and E M de Jong, and E S de Bakker, and P C van de Kerkhof
Department of Dermatology, University Hospital Nijmegen, The Netherlands. J.vanPelt@Derma.AZN.NL

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.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D009426 Netherlands Country located in EUROPE. It is bordered by the NORTH SEA, BELGIUM, and GERMANY. Constituent areas are Aruba, Curacao, and Sint Maarten, formerly included in the NETHERLANDS ANTILLES. Holland,Kingdom of the Netherlands
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D011565 Psoriasis A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. Palmoplantaris Pustulosis,Pustular Psoriasis of Palms and Soles,Pustulosis Palmaris et Plantaris,Pustulosis of Palms and Soles,Psoriases
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D003872 Dermatitis Any inflammation of the skin. Dermatitides
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme

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