Causal Analysis Shows Evidence of Atopic Dermatitis Leading to an Increase in Vitamin D Levels

Drodge, Daniel; Budu-Aggrey, Ashley; Paternoster, Lavinia

doi:10.1016/j.jid.2020.09.013

Cited by 11 publications

(9 citation statements)

References 24 publications

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“…Interestingly, a recent MR study [37] showed that AD causes increased 25(OH)D, even after adjusting for VD supplementation. The mechanism for this observation is unclear but it has been proposed that an AD diagnosis may prompt behavioral changes that result in greater UV exposure or VD Fig.…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted that the authors of the MR study performed sensitivity analyses and ensured that the validity of MR instrumental variables as defined by key MR assumptions of relevance, independence, and exclusion restriction were not violated [37]. They employed genetic instruments strongly associated with exposure and were independent with no unmeasured confounders as well as investigating for horizontal pleiotropy [39].…”

Section: Discussionmentioning

confidence: 99%

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Effect of Vitamin D Serum Levels and Supplementation on Atopic Dermatitis: A Systematic Review and Meta-analysis

Ng¹,

Yew

2022

Am J Clin Dermatol

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Background Previous studies have shown that serum 25-hydroxyvitamin D (25(OH)D) may be associated with atopic dermatitis (AD), and that vitamin D (VD) supplementation may decrease AD severity. Objective The aim of this study was to investigate the association between serum 25(OH)D level and AD, and the effect of VD supplementation on AD severity, while providing stratified analyses based on latitude and region. Methods A systematic review was performed on all published studies in MEDLINE, Embase, and Cochrane Library databases that analyzed effects of serum 25(OH)D and VD supplementation on AD. Results This systematic review and meta-analysis includes 20 studies with 1882 cases of AD. We found significantly lower 25(OH)D levels in AD patients compared with healthy controls (HC) (p < 0.001), significantly lower 25(OH)D levels in severe AD compared with both mild and moderate AD (p < 0.001), and VD supplementation improved AD symptoms (p < 0.001). Limitations Factors like seasonal and environmental changes, sunlight exposure, and cultural practices may confound the relationship between serum 25(OH)D and AD severity. There are limited randomized controlled trials that assess this association. Conclusion Overall, lower serum 25(OH)D is associated with more severe AD, and VD supplementation may help lower AD severity. Further research is needed to confirm the presence and direction of causality of the relationship between VD and AD pathogenesis. Key PointsAtopic dermatitis (AD) patients had significantly lower 25-hydroxyvitamin D (25(OH)D) levels compared with healthy controls. Patients with severe disease had lower 25(OH)D levels than patients with mild and moderate disease. AD symptoms improved after vitamin D (VD) supplementation.Further research on efficacy and optimal dosage of VD supplementation in AD treatment is required.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Vitamin D Serum Levels and Supplementation on Atopic Dermatitis: A Systematic Review and Meta-analysis

Ng¹,

Yew

2022

Am J Clin Dermatol

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“…As another example of possible demographics-driven differences in trial and MR results, MR studies on the relationship between vitamin D levels and atopic dermatitis were conducted in the general population 74,75 , while RCTs were conducted separately in children in Mongolia 76 and Boston, USA 77 with winter atopic dermatitis and in adolescent and adult Iranians 78,79 .…”

Section: ) Source Populationmentioning

confidence: 99%

“…However, the best disease GWAS used to identify MR instruments often represent binary disease outcomes, which could potentially lead to differential conclusions due to reduced power to detect subtler therapeutic effects. While exercise is causally associated with reduced depression and depressive symptoms both in MR 68,69 and RCTs 55,67,[70][71][72][73] , the differences in outcome phenotypes could potentially contribute to null MR results 74,75 and positive effect of vitamin D on attenuating eczema symptoms in RCTs [76][77][78][79] .…”

Section: ) Outcomementioning

confidence: 99%

Systematic comparison of Mendelian randomization studies and randomized controlled trials using electronic databases

Sobczyk

Smith

Gaunt

2022

Preprint

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Mendelian Randomization (MR) uses genetic instrumental variables to make causal inferences. Whilst sometimes referred to as "nature's randomized trial", it has distinct assumptions that make comparisons between the results of MR studies with those of actual randomized controlled trials (RCTs) invaluable. To scope the potential for (semi-)-automated triangulation of MR and RCT evidence, we mined ClinicalTrials.Gov, PubMed and EpigraphDB databases and carried out a series of 26 manual literature comparisons among 54 MR and 77 RCT publications. We found that only 11% of completed RCTs identified in ClinicalTrials.Gov submitted their results to the database. Similarly low coverage was revealed for Semantic Medline (SemMedDB) semantic triples derived from MR and RCT publications - 25% and 12%, respectively. Among intervention types that can be mimicked by MR, only trials of pharmaceutical interventions could be automatically matched to MR results due to insufficient annotation with MeSH ontology. A manual survey of the literature highlighted the potential for triangulation across a number of exposure/outcome pairs if these challenges can be addressed. We conclude that careful triangulation of MR with RCT evidence should involve consideration of similarity of phenotypes across study designs, intervention intensity and duration, study population demography and health status, comparator group, intervention goal and quality of evidence.

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“…13 Reverse causation was found in another Mendelian randomized analysis that evidenced genetic risk of atopic dermatitis with increased vitamin D levels. 14 Vitamin D deficiency was associated with higher levels of IgE sensitization in children and adolescents in the large, populationwide National Health and Nutrition Examination Survey (NHANES) in the United States. 15 We aimed to evaluate whether 25-hydroxyvitamin D status is related to specific IgE levels for the most frequent allergens in our community, regardless of clinical manifestations.…”

Section: Introductionmentioning

confidence: 99%

Association between vitamin D status and allergen sensitization in pediatric subjects in the Balearic Islands

Segovia‐Ortí

Bennasar

Sotto-Esteban

et al. 2021

Pediatric Allergy Immunology

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Introduction: Vitamin D has known effects on the immune system, and its deficiency has been associated with allergen sensitization. Material and methods: A retrospective study was performed to evaluate the association between 25(OH)vitamin D (25(OH)D) and specific IgE for the most frequent allergens in our area in children and adolescents. All subjects under 15 years of age with a determination of Phadiatop ® or Phadiatop Infant ® and close serum 25(OH)D determination were included, from 2012 to 2019. From this sample, demographic and analytical variables were collected: specific IgE to Dermatophagoides pteronyssinus;dog and cat dander; grass, olive, and pellitory pollens; egg white; and cow milk; as well as complete blood count analysis and immunoglobulins.Results: A total of 749 subjects were recruited. Clusters according to deficiency, insufficiency, or sufficiency of 25(OH)D showed an association with age, Phadiatop ® , D. pteronyssinus, cat and dog dander specific IgE, and a higher frequency of positive allergen sensitization (P < .05). Logistic regression, compared with vitamin D levels of greater than 30 ng/mL after age adjustment, showed that deficient 25(OH)D was associated with D. pteronyssinus (OR 1.90; 95% CI, 1.25-2.90) and dog dander (OR, 2.10; 1.10-4.02); whereas insufficient 25(OH)D was associated with cat dander (OR, 2.46;) and also with D. pteronyssinus (OR, 1.55; 1.06-2.29) (P < .05). No associations were found between 25(OH) D levels and other analytical parameters. Conclusion:Vitamin D status is associated with sensitization to D. pteronyssinus, and cat and dog dander in children and adolescents, and also with a higher number of positive specific IgE.

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Causal Analysis Shows Evidence of Atopic Dermatitis Leading to an Increase in Vitamin D Levels

Cited by 11 publications

References 24 publications

Effect of Vitamin D Serum Levels and Supplementation on Atopic Dermatitis: A Systematic Review and Meta-analysis

Effect of Vitamin D Serum Levels and Supplementation on Atopic Dermatitis: A Systematic Review and Meta-analysis

Systematic comparison of Mendelian randomization studies and randomized controlled trials using electronic databases

Association between vitamin D status and allergen sensitization in pediatric subjects in the Balearic Islands

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