title: 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 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.
authors.affiliation: Department of Dermatology, University Hospital Nijmegen, The Netherlands. J.vanPelt@Derma.AZN.NL
authors.forename: J P
authors.initials: JP
authors.lastname: van Pelt
authors.forename: E M
authors.initials: EM
authors.lastname: de Jong
authors.forename: E S
authors.initials: ES
authors.lastname: de Bakker
authors.forename: P C
authors.initials: PC
authors.lastname: van de Kerkhof
mesh_terms: D000328:Adult; D015415:Biomarkers; D001706:Biopsy; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D003872:Dermatitis / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004817:Epidermis / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D009426:Netherlands; D011446:Prospective Studies; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D015415:Biomarkers; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D019394:Ki-67 Antigen; C061121:liarozole