Systemic treatment of psoriatic patients with bexarotene decreases epidermal proliferation and parameters for inflammation, and improves differentiation in lesional skin - 24/08/11
Nijmegen, The Netherlands
Abstract |
Background |
Bexarotene, a novel synthetic retinoid X receptor (RXR)–selective retinoid, has been reported to have antiproliferative and apoptotic stimulating effects in cutaneous T-cell lymphoma. In benign, hyperproliferative, and retinoid sensitive disorders, such as psoriasis, bexarotene has not been evaluated so far and no information on these parameters is available.
Objective |
In the present study, immunohistochemical parameters for proliferation, differentiation, inflammation, and apoptosis were investigated in a group of bexarotene-treated psoriatic patients.
Methods |
Twenty-nine patients with plaque-type psoriasis were treated for 12 weeks with oral bexarotene in four dose-defined treatment panels. Treatment was initiated in the following consecutive order: 1.0 mg/kg/day, 2.0 mg/kg/day, 0.5 mg/kg/day, and 3.0 mg/kg/day. Biopsies for immunohistochemical analysis were taken at the baseline and after 12 weeks of treatment.
Results |
Significant reductions in Ki-67, keratin 16, transglutaminase, dermal CD4, epidermal CD8, and inflammation scores were seen after bexarotene treatment in combination with a significant increase in keratin 10. No induction of keratin 13 and 19 and no alterations in apoptosis associated p53 expression were observed. Apart from a weak significant dose-response effect for Ki-67, no other significant dose-response effects were seen.
Conclusion |
We have demonstrated efficacy of oral bexarotene in psoriasis in doses up to 3.0 mg/kg/day during 12 weeks of treatment for proliferation, differentiation, and inflammation parameters. Studies investigating higher doses of bexarotene in a larger number of patients are necessary to reveal potentially dose-related immunohistochemical effects of this new rexinoid and to elucidate the role of RXR-signaling in retinoid-associated keratin expression.
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Funding sources: None. Conflicts of interest: None identified. A part of this work has been presented in a poster session at the Psoriasis From Gene to Clinic congress in London in December 1999, and as a plenary paper at the SID congress in Chicago in May 2000. |
Vol 51 - N° 2
P. 257-264 - août 2004 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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