A novel approach for the evaluation and treatment of psoriasis. Oral or topical use of 1,25-dihydroxyvitamin D3 can be a safe and effective therapy for psoriasis.

We investigated the effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) on cultured fibroblasts and keratinocytes from patients with psoriasis and treated 17 patients with psoriasis with orally or topically administered 1,25-(OH)2-D3. Cultured fibroblasts from three of five patients showed a normal response to the antiproliferative activity of a physiologic dose of 1,25-(OH)2-D3, whereas fibroblasts from the other two had a partial resistance to the drug. Cultured keratinocytes from two patients with psoriasis possessed nuclear receptors for 1,25-(OH)2-D3 and the drug caused a dose-dependent inhibition of proliferation and induction of terminal differentiation of these cells similar to effects in normal cultured keratinocytes. Ten of 14 patients with moderate to severe psoriasis who received oral 1,25-(OH)2-D3 showed significant clearing of their hyperkeratotic plaques. Three patients had complete clearing that was sustained with maintenance therapy, but four patients received little or no benefit from the therapy. By the administration of 1,25-(OH)2-D3 as a single oral dose at bedtime, larger doses of the drug could be tolerated without evidence of hypercalciuria or hypercalcemia. Three patients who received topical 1,25-(OH)2-D3 showed a rapid response with complete clearing after 6 weeks of therapy. Therefore, these preliminary findings suggest that orally or topically administered 1,25-(OH)2-D3 may be a safe and effective alternative therapy for the treatment of psoriasis.