Synthetic retinoids that have distinct therapeutic activity on psoriatic plaques act at least in part through the metabolic pathways of natural retinoids. The metabolism of retinol, retinal, and retinoic acid in human epidermis in general and psoriatic plaques in particular has not been previously analyzed. This appears to be an important issue, because enzymatic formation of retinoic acid from retinol within target cells is thought to be the source of biologically active retinoic acid therein and might be subjected to regulation. We found chat the enzymatic system that transforms (3H)retinol into (3H)retinoic acid is detectable in psoriatic plaques (0.33 +/- 0.07 pmol/h/mg protein) but only in trace amounts in normal epidermis. The activity due to alcohol deshydrogenase seems not to be involved in this process. (3H)retinal was found to be either reduced into retinol or oxidized into retinoic acid, depending on the ratio of NAD to NADH (the oxidized arid reduced nicotinamide-adenine dinucleotide, respectively); the former reaction was higher in psoriatic plaques than in normal epidermis.

The analogue of calcitriol calcipotriol (MC 903 Daivonex®) has been proven effective in the treatment of psoriasis, when given topically. However, the possible influence of cutaneously absorbed MC 903 on calcium metabolism is still unclear. We evaluated various parameters of calcium metabolism in 17 psoriatic patients treated for 5.4 ± 2.3 (mean ± SD) weeks with MC 903, on 16 ± 6% of the body surface. The dose administered (100 g of Daivonex corresponding to 5 mg of MC 903) decreased the PASI score by 40.9 ± 20.0% (p < 0.001). Among these patients, 12 were studied before and after MC 903 therapy. In none could be detected any change in protein-adjusted calcium, ionized Ca, plasma levels of creatinine, alkaline phosphatase, osteocalcin, intact parathyroid hormone (PTH), calcidiol and calcitriol, or in daily or fasting urinary excretion of Ca or cAMP. After an MC-903-free period, 9 patients received 1.5 μg/day of calcitriol orally for 7 days. Whereas this treatment did not control the skin relapse in most of the patients, it induced a significant increase in plasma levels of protein-adjusted Ca and calcitriol, and in 24-hour urinary Ca excretion, as well as a significant fall in PTH as compared with pretreatment values. These results indicate that 150 μg/day of MC 903 despite a possible 1% absorption i. e. a systemic dose of 1.5 μg did not produce any detectable alteration of Ca metabolism, whereas an equivalent dose of oral calcitriol was associated with significant changes. The threshold dose of topical calcipotriol that might induce alterations similar to 1.5 μg/day of oral calcitriol remains to be evaluated.

The topical application of 0.1% retinoic acid (RA) on human skin over a period of 4 days, whether or not under occlusion, did not increase either IL-1 alpha or beta immunoreactivity as determined by a sensitive enzymoimmunoassay. No down modulation was seen following the application of a potent topical corticosteroid. Occlusion increased the yield of IL-1 beta immunoreactivity. Immunoblot patterns of epidermal extracts revealed both the mature form of IL-1 (17 kDa) and the precursor (36 kDa) and were identical in amounts whether the specimens were from controls or from RA- or corticosteroid-treated skin. There was a slight modification in the pattern of high molecular weight proteins (52 kDa) probed by the anti-IL-1 alpha and beta sera. It appears that the IL-1 epidermal immunoreactive pools are barely amenable to modulation because they represent a storage form linked to end-stages of keratinocyte differentiation.

Background: The vitamin D₃ derivative calcipotriol (Daivonex®) is an efficient topical treatment of psoriasis. When applied at a dose of about 25 g/week over a mean body surface of 16%, it is not associated with any detectable change in calcium metabolism. Objective: Our purposes were (i) to analyze the effects of calcipotriol on various parameters of calcium metabolism when applied on a large body surface and (ii) to evaluate the usefulness of an oral calcium tolerance test in monitoring psoriatic patients under topical calcipotriol. Methods: In group 1, 10 patients with psoriasis affecting 67.0 ± 2.7% of total body surface (range 55–80%) were treated with calcipotriol for 6.5 weeks (mean 383 g/month). In group 2, 19 patients with psoriasis involving 15% of body surface were treated with calcipotriol for 9 weeks (mean 105 g/month). In group 3, 7 patients without topical calcipotriol for at least 1 week were given 1.5 μg of oral calcitriol for 7 days. An extended survey of blood and urinary parameters of calcium metabolism was performed before and after 45 days of treatment (group 1). Since one of the actions of vitamin D is to stimulate intestinal calcium absorption, an oral calcium-loading test (groups 1, 2 and 3) was done in order to detect more subtle changes possibly induced by calcipotriol. Results: We did not detect any significant change in various parameters of calcium metabolism in group 1 (large body surface treated) patients. The urinary calcium responses to the oral calcium load were identical to controls in both group 1 (large body surface treated) and group 2 (limited body surface treated), whereas in group 3 (oral calcitriol therapy) an increased urinary calcium response to the calcium load was identified. Conclusions: No significant changes in calcium metabolism were detectable when calcipotriol was administered once a day over a large body surface with doses up to 100 g/week. The oral calcium tolerance test appears to be a cheap, simple and sensitive test to monitor patients exposed to high doses of calcipotriol as it detects increased intestinal calcium absorption induced by 1.5 μg of oral calcitriol.