Topical treatment by urea reduces epidermal hyperproliferation and induces differentiation in psoriasis

The mechanisms of action of urea-containing ointments in the treatment of eczema, ichthyosis and psoriasis are only partly known and related to proteolysis and keratinolysis. In this study, we have examined the effects of topical urea on epidermal proliferation and differentiation in 10 patients with psoriasis. Plaque type lesions were treated for 2 weeks with an ointment containing 10% urea, with the vehicle alone, or left untreated. Clinical score, hydration of the stratum corneum, transepidermal water loss (TEWL), and immunohistochemical studies were performed. Epidermal proliferation was assessed using the Ki-S3 proliferation-associated nuclear antigen. For epidermal differentiation antibodies against involucrin and against keratins CK 5, 6, 17 and CK 1, 5, 10, 14 were used. The patients showed a reduction of the clinical score (> 50%), a 2-fold increase in stratum corneum hydration (p < 0.01), and a small decrease in TEWL (N.S.) on the urea- treated compared to the untreated site. Light microscopy studies revealed a 29% reduction in epidermal thickness (p < 0.01); epidermal proliferation was decreased by 51% (p < 0.005). The altered expression of involucrin and of cytokeratins (reduction of CK 5, 1 and 10 and induction of CK 6 and 17) was partially reversed. The ointment base also improved psoriasis, but urea was significantly better than the vehicle (urea: 40% reduction in epidermal proliferation vs. vehicle). In summary, these studies show that urea influences epidermal proliferation and differentiation in psoriasis.