PMID- 9988537
OWN - NLM
STAT- MEDLINE
DCOM- 19990209
LR  - 20190704
IS  - 0007-0963 (Print)
IS  - 0007-0963 (Linking)
VI  - 139
IP  - 3
DP  - 1998 Sep
TI  - The effects of oral liarozole on epidermal proliferation and differentiation in 
      severe plaque psoriasis are comparable with those of acitretin.
PG  - 380-9
AB  - 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 plasma and skin. As part 
      of a large, double-blind, randomized clinical study, we investigated the cell 
      biological alterations in uninvolved and lesional skin of 20 patients with severe 
      plaque psoriasis, who were treated with either liarozole or acitretin. The extent 
      and severity of the skin lesions, as recorded by the Psoriasis Area and Severity 
      Index score, was significantly reduced (P </=0.05) after 12 weeks of treatment in 
      both the acitretin- and the liarozole-treated group. A significant decrease in 
      the markers for inflammation (neutrophils), epidermal proliferation 
      (Ki-67-positive cells), normal differentiation (transglutaminase) and abnormal 
      differentiation [cytokeratin 16 and skin-derived antileucoproteinase (SKALP), 
      also known as elafin] was seen in both groups. No significant differences were 
      noted in clinical scores or cell biological scores between the liarozole- and 
      acitretin-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 remaining positive. SKALP 
      levels in serum fell in both groups with similar kinetics and showed a 
      statistically significant correlation with clinical 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 spinous layers, which is not found in normal human skin. Although 
      the mechanism of action differs fundamentally, liarozole and acitretin show 
      similar effects with respect to clinical effects and cell biological changes in 
      the lesional and non-lesional skin.
FAU - Kuijpers, A L
AU  - Kuijpers AL
AD  - Department of Dermatology, University Hospital Nijmegen, The Netherlands. 
      a.kuijpers@derma.azn.nl
FAU - Van Pelt, J P
AU  - Van Pelt JP
FAU - Bergers, M
AU  - Bergers M
FAU - Boegheim, P J
AU  - Boegheim PJ
FAU - Den Bakker, J E
AU  - Den Bakker JE
FAU - Siegenthaler, G
AU  - Siegenthaler G
FAU - Van de Kerkhof, P C
AU  - Van de Kerkhof PC
FAU - Schalkwijk, J
AU  - Schalkwijk J
LA  - eng
PT  - Case Reports
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Imidazoles)
RN  - 0 (Keratolytic Agents)
RN  - 0 (Proteinase Inhibitory Proteins, Secretory)
RN  - 0 (Proteins)
RN  - 0 (Serine Proteinase Inhibitors)
RN  - K0Q29TGV9Y (liarozole)
RN  - LCH760E9T7 (Acitretin)
SB  - IM
MH  - Acitretin/*therapeutic use
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Double-Blind Method
MH  - Epidermis/*drug effects/pathology
MH  - Female
MH  - Humans
MH  - Imidazoles/*administration & dosage/pharmacology
MH  - Immunoenzyme Techniques
MH  - Keratolytic Agents/*administration & dosage/pharmacology
MH  - Leukocyte Count/drug effects
MH  - Male
MH  - Middle Aged
MH  - Proteinase Inhibitory Proteins, Secretory
MH  - Proteins/metabolism
MH  - Psoriasis/*drug therapy/pathology
MH  - Serine Proteinase Inhibitors/blood
EDAT- 1999/02/13 00:00
MHDA- 1999/02/13 00:01
CRDT- 1999/02/13 00:00
PHST- 1999/02/13 00:00 [pubmed]
PHST- 1999/02/13 00:01 [medline]
PHST- 1999/02/13 00:00 [entrez]
AID - 10.1046/j.1365-2133.1998.02399.x [doi]
PST - ppublish
SO  - Br J Dermatol. 1998 Sep;139(3):380-9. doi: 10.1046/j.1365-2133.1998.02399.x.