Vitamin D supplementation in polymorphic light eruption

Polymorphic light eruption (PLE) is a common photodermatosis with a high prevalence of approximately 11 to 21% in the population. Similar to lupus erythematosus (LE), an UV-inducible systemic autoimmune disease, PLE has a female preponderance with a mean onset in the second to third decade of life. PLE lesions are very itchy and typically appear on sun-exposed body sites in spring or early summer. The quality of life in patients with PLE is often severely disturbed, as evidenced by high levels of anxiety and depression. For prophylaxis besides conventional sunscreens, photo(chemo)therapy is effective in many cases, when administered over several weeks for hardening in early spring before the first natural sun exposure takes place. However, because pro-longed treatment with UVB and/or photochemotherapy is potentially carcinogenic, the search for pathogenic mechanisms and new treatment options in PLE is ongoing. The exact pathogenesis of PLE is currently unknown but findings suggest an autoimmune-type background with resistance to UV-induced immune suppression and simultaneous immune reactions against skin photo-neoantigens. We have recently found that PLE patients had significantly reduced 1,25-(OH)2-vitamin D3 serum levels (13-14ng/ml) compared to the normal population (>30ng/ml). In addition, we were able to demonstrate in an intra-individual half-body trial that topical administration of an immunostimmulatory 1,25-(OH)2-vitamin-D3 analogue calcipotriol reduced PLE symptoms in an experimental study. In the proposed randomized double-blinded placebo-controlled trial we attempt to study the effect of oral vitamin D3 supplementation (40.000 IE given orally at week 0 and 2) on PLE symptoms. PLE patients will be subjected to experimental photoprovocation with solar simulated UV radiation over several days before and after vitamin D3 supplementation. Disease symptoms will be quantified with a newly established and validated PLE test score, (AA + SI + 0.4P [range, 0-12], where AA is affected area score [range, 0-4], SI is skin infiltration score [range, 0-4], and P is pruritus score on a visual analogue scale [range, 0-10]). We will also study the effect of oral vitamin D3 on abnormalities i) in levels and function of regulatory T cells, ii) chemotaxis of leucocytes, and iii) proinflammatory cytokines, i.e. alterations that we have previously linked to PLE pathogenesis. This will be done by i) FACS and co-culture T cell proliferation assays, ii) response of peripheral neutrophil leucocytes to the chemoattractants leukotriene B4 (LTB4) and formyl-methionyl-leucyl-phenylalanin, and iii) ELISA and immuno bead assay of patient serum. The results of the project will enlighten the mechanism of PLE and may establish the base of a novel prevention strategy via the vitamin D3 pathway.

Polymorphic light eruption (PLE) is the most common form of a sun allergy that occurs in approximately 10 to 20% of the population and particularly young women. The skin lesions of PLE are very itchy and appear on sun-exposed body sites after the first intense exposure in spring or early summer. The quality of life in diseased patients is often severely disturbed. The influence of UV radiation on the human body leads to suppression of the immune system, i.e. the overthrow of the body's own defense system. This immune suppression seems to have a defense function against the formation of PLE that is most likely directed against sun-produced, newly formed antigens. Patients with PLE exhibit an increased resistance against UV-induced immune suppression that allows an immune response to be mounted (that in normal subjects would be suppressed) and hereby the formation of PLE. The severity of skin symptoms of patients usually is abating as the season progresses as a result of subsequent sun exposures and a so called hardening effect. Such a hardening can also be achieved through medical photohardening with repeated exposure to artificial UV radiation over several weeks. In this project effectors were investigated in the course of the season, that if missing or dysfunctional, may be involved in the pathogenesis of PLE. In particular the role of vitamin D was addressed. In recent years besides the known influence of vitamin D on calcium and phosphate levels a crucial role of this vitamin in immune regulation was discovered. The results of this study revealed that approximately 30% of patients with PLE had in spring decreased vitamin D serum levels, which improved towards summer. Medical UV hardening resulted in a significant increase of regulatory T cells (Tregs) by approximately 30 to 60% in the blood of the patients. Tregs are crucial for the suppression of embroidered immune responses. This increase correlated with an increased function of those cells. A direct correlation between the elapsing time in the season and the serum levels of vitamin D was observed. However, there was no relationship of season or vitamin D with Treg levels and function. This indicates that Treg number and function are at least in PLE patients independent from vitamin D serum levels and rather depend from the input of UV radiation and/or other seasonal factors. Together this suggests that a beneficial effect in PLE can't be expected from medical vitamin D administration.