Therapeutic Effects of Tazarotene on Psoriasis and Its Potential Action Mechanism in Inflammatory Angiogenesis

Ku, Bon Seok; Lee, Chae Wook; Kim, Ki Ho

Abstract

BACKGROUND: Psoriasis is characterized by chronic recurrent erythematous skin plaques that exhibit epidermal hyperplasia, inflammatory cell accumulation and abnormalities of the papillary dermal vasculature. Psoriatic skin lesions show enlargement and increased tortuosity of cutaneous microvessels without formation of new vessel sprouts, that is, inflammatory angiogenesis. Placental growth factor (PlGF) and Tie-2 were reported to be up-regulated during inflammatory angiogenesis. Tazarotene is the first receptor-selective retinoid and its effects include normalizing keratinocyte differentiation, reducing keratinocyte proliferation and reducing inflammation.
OBJECTIVE
Our study evaluated the clinical efficacy of topical tazarotene treatment and clarified histological changes and possible action mechanisms of this agent in respect of inflammatory angiogenesis.
METHODS
We selected patients with symmetric psoriatic lesions and applied 0.1% tazarotene gel (Tazorac(R)) versus calcitriol 3 microgram/g gel (Silkis(R)) twice a day for 12 weeks with a right-left comparison. We grouped the patients with treatment modalities. Clinical efficacy, which was measured by the overall lesional assessment (OLA) scores, was assessed at each visit in 2 week' intervals until treatment closed. Skin biopsies were performed before the treatment started and again at 4 weeks and 12 weeks after treatment. Immunohistochemistry of PlGF, Tie-2 and factor-VIII was performed to elucidate the anti-angiogenetic effect of tazarotene.
RESULTS
At the completion of 12 weeks of treatment, the OLA score of tazarotene-treated lesions was more reduced than that of calcitriol-treated lesions combined with phototherapy, it was more effective. Several histologic features such as epidermal hyperplasia, inflammatory cell infiltration and vessel dilation/tortousity were improved with decreased PlGF and Tie-2 expressions.
CONCLUSION
These results indicate that tazarotene is an effective topical agent for psoriasis by blocking inflammatory angiogenesis.