Systemic treatment of psoriatic patients with bexarotene decreases epidermal proliferation and parameters for inflammation, and improves differentiation in lesional skin.
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.


CONCLUSIONS
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.
Smit
Jürgen V
JV
Department of Dermatology, University Medical Center, Nijmegen, The Netherlands.
de Jong
Elke M G J
EM
van Hooijdonk
Candida A E M
CA
Otero
Marisol E
ME
Boezeman
Jan B M
JB
van de Kerkhof
Peter C M
PC
D000284:Administration, Oral; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D000077610:Bexarotene; D001707:Biopsy, Needle; D002454:Cell Differentiation / Q000187:drug effects; D003872:Dermatitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004817:Epidermis / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D019394:Ki-67 Antigen / Q000378:metabolism; D011565:Psoriasis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology / Q000627:therapeutic use*
D019394:Ki-67 Antigen; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene