Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial.

BACKGROUND: Vitamin D (VD) deficiency is common among patients with atopic dermatitis (AD) and often associated with severity. However, randomized trials of VD supplementation in AD have had equivocal results, and there is little information regarding the effect of VD supplementation on type 2 immunity in AD patients. OBJECTIVES: To investigate the efficacy of VD supplementation to decrease severity of AD and to alter type 2 immunity biomarkers. METHODS: We performed a randomized, double-blind, placebo-controlled trial. We randomly assigned 101 children with AD to weekly oral vitamin D3 (VD3) or placebo for 6 weeks. The primary outcome was the change in the Severity Scoring of AD (SCORAD). RESULTS: Mean age of subjects was 6.3 ± 4.0 years, and baseline SCORAD was 32 ± 29. At baseline, 57% of children were VD deficient, with no difference between groups. Change in 25(OH)D was significantly greater with VD3 than placebo (+43.4 ± 34.5 nmol/L vs. +2.3 ± 21.2 nmol/L, p < 0.001). SCORAD change at 6 weeks was not different between VD and placebo (-5.3 ± 11.6 vs. -5.5 ± 9.9, p = 0.91). There were no significant between-group differences in change of eosinophil counts, total IgE, Staphylococcal enterotoxin specific IgE, CCL17, CCL22, CCL27, LL-37 or Staphylococcus aureus lesional skin colonization. Vitamin D receptor (VDR) gene single nucleotide polymorphisms FokI, ApaI and TaqI did not modify subjects' response to VD supplementation. CONCLUSIONS: Among children with AD, weekly VD supplementation improved VD status but did not modify AD severity or type 2 immunity biomarkers compared to placebo (ClinicalTrials.gov NCT01996423).

Oral vitamin D modulates the epidermal expression of the vitamin D receptor and cathelicidin in children with atopic dermatitis.

Although vitamin D (VD) is known to have multiple effects on the skin and immunity, its effects on atopic dermatitis (AD) severity remain unclear. We investigated whether oral cholecalciferol (VD3) supplementation changes stratum corneum expression of the vitamin D receptor (vdr), and the epidermal alarmins Cathelicidin Antimicrobial Peptide (camp/LL-37) and Thymic Stromal Lymphopoietin (tslp) in children with AD. We conducted an open-label supplementation study with weekly oral VD3 for six weeks in children with AD. Serum 25-hydroxyvitamin D (25OHD), lesional Staphylococcus aureus colonization, and AD severity evaluated by SCORAD index were evaluated before and after supplementation. Tape stripping (TS) was performed on non-lesional and lesional skin to measure mRNA expression of vdr, camp, and tslp through RT-qPCR and LL-37 peptide by ELISA. Twenty-two children with moderate-severe AD received weekly oral VD3 for six weeks. Total serum 25OHD increased from 45.1 ± 23 to 93.5 ± 24.3 nmoL/L (p < 0.0001), while SCORAD decreased from 41.4 ± 13.5 to 31.5 ± 15.8 (p < 0.0001). After treatment, epidermal gene expression of camp increased significantly in non-lesional (p = 0.014) and lesional (p = 0.0007) tape stripping samples, while vdr only increased in lesional skin samples (p < 0.0001). LL-37 peptide increased significantly only in lesional skin samples (p = 0.008). Gene expression of tslp did not change after oral VD3 treatment. In children with AD, oral VD3 supplementation was associated with improved VD status and AD severity, as well as increased VDR and Cathelicidin expression in lesional skin, which provide mechanistic clues on its effects.

Vitamin D status and supplementation in Antarctica: a systematic review and meta- analysis.

Living at high latitudes is associated with vitamin D (VD) deficiency. An ideal setting to study this is the Antarctic continent, which has temporary inhabitants, but the magnitude of the effect of living in Antarctica and the effects of VD supplementation on this population remain unclear. We performed a systematic review and meta-analysis to assess the effect of temporary residence in Antarctica and impact of VD supplementation on VD status of this population. Random-effects meta-analyses were performed to assess serum 25-hydroxyvitamin D (25(OH)D) concentration changes after Antarctic residence (13 studies, 294 subjects) and after VD supplementation (5 studies, 213 subjects). Serum 25(OH)D mean difference after temporary residence in Antarctica was -15.0 nmol/L (95%CI: -25.9, -4.2; I²=92%). Subgroup meta-analyses of studies evaluating Antarctic summer and winter stays showed 25(OH)D only decreases when overwintering (winter 25(OH)D change -17.0 nmol/L [95%CI: -24.1, -9.8; I²=83%] vs. summer 25(OH)D change 1.3 nmol/L [95%CI: -14.6, 17.1; I²=86%]). The meta-analysis of VD supplementation studies in Antarctica showed a mean 25(OH)D increase after supplementation of 10.8 nmol/L (95%CI: 3.3, 18.3; I²=88%). In conclusion, VD status significantly worsens after inhabiting Antarctica, particularly when over-wintering. VD supplementation can prevent worsening of VD status and should be considered in this population.

Vitamin D modulates the allergic phenotype of dendritic cells in children with atopic dermatitis.

Vitamin D (VD) deficiency has been associated with increased incidence and severity of atopic dermatitis (AD), but the mechanisms through which VD may ameliorate AD are unclear. We compared the phenotypic characteristics of circulating myeloid and plasmacytoid dendritic cells (mDCs and pDCs, respectively) of children with AD vs healthy controls (HC) and evaluated if VD can modulate the allergic phenotype of circulating DCs in AD patients. Although there was no difference in frequency of circulating DCs between groups, among children with AD there was an inverse correlation between SCORAD and circulating total DCs and mDCs. In AD, serum IgE concentration correlated with FcεRI and surface-bound IgE expression on mDCs and pDCs; pDCs expressing FcεRI and IgE were significantly increased compared to HC. Ex vivo, 1,25(OH)2 D3 significantly decreased FcεRI expression on mDCs and surface-bound IgE on mDCs and pDCs. Oral VD supplementation reduced expression of surface-bound IgE on pDCs in children with AD. In summary, VD decreases the allergic phenotype of circulating DCs in children with AD, a potential mechanism for how VD supplementation may improve AD severity. Future studies are needed to further assess the role of VD supplementation as an immunomodulatory therapy for AD.