Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disorder with a complex pathogenesis including genetic, immunologic, hormonal and environmental factors. Among environmental modulators of SLE, vitamin D has been increasingly investigated over the years. Such interest derived from several observations: 1) SLE patients are particularly prone to vitamin D insufficiency due to the avoidance of sun exposure, but in some cases also because of the renal involvement of the disease or medications; 2) in vitro studies have demonstrated that vitamin D is able to modulate several different cell types (dendritic cells, T and B cells) with effects that may be beneficial in autoimmune diseases; 3) animal models of SLE have shown disease amelioration upon supplementation with vitamin D.
Recent review papers and meta-analyses confirmed that vitamin D insufficiency is widespread in SLE, affecting 38–96% of the patients. What needs to be still clarified is the relationship between low levels of vitamin D and disease activity/severity and whether vitamin D supplementation can be useful to positively influence the course of the disease. There is trend toward an inverse relationship between vitamin D insufficiency and higher disease activity, although many studies failed to describe it. In addition, vitamin D insufficiency seems to be related to cardiovascular events in SLE patients, although this association may be mediated by “traditional” cardiovascular risk factors. Interventional studies are still limited in number and did not reach definite conclusions in terms of optimal vitamin D supplementation to be applied in SLE patients.
It should be acknowledged that different results across studies may be due to methodological issues. In fact, the outcomes of a study investigating the role of vitamin D can be affected by many variables: demographic factors (age, ethnicity, body mass index, nutritional intake), sample size of the cohort and study design, compound used for supplementation (cholecalciferol vs. ergocalciferol), dosage and timing (low vs. high dose; daily/weekly/monthly schedule), outcomes of the study (variations in indices of SLE disease activity, cytokines and lymphocyte populations, inflammatory and hemostatic markers, or IFNalfa signature). By measuring 25-OH vitamin D levels, clinical studies do not get a direct picture of the actual activity of the vitamin D system. Additional relevant information may come from the evaluation of the active form 1,25-OH vitamin D and from the analysis of the polymorphisms of the vitamin D receptor.
In the clinical setting, every SLE patient should be assessed for circulating levels of 25-OH vitamin D. Supplementation should be tailored upon the individual vitamin D status and other characteristics (obesity, renal failure, etc.). Especially in those patients taking steroids and at a higher risk of osteoporosis, vitamin D levels should be kept in the range of sufficiency (above 30 ng/ml). The fascinating immunomodulatory role of vitamin D needs to be confirmed in the clinical setting in order to support a more intensive treatment with vitamin D in SLE patients. Nonetheless, it should be considered that vitamin D is a cheap intervention with an excellent safety profile, so the routine use of moderate doses of cholecalciferol (1000–2000 UI/day) in SLE patients should not raise any major concern.
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Disclosure of Interest None declared
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