Marilynn Larkin
Vitamin D levels are unlikely to have an impact on the clinical features of eosinophilic esophagitis (EoE) in adults newly diagnosed with the chronic inflammatory disorder, new research suggests.
The substantial increase in EoE incidence and the association of low vitamin D levels with increased risk for allergic sensitization prompted the researchers to assess whether vitamin D levels were lower in patients newly diagnosed with EoE than in people without the disease, and whether the levels affected EoE clinical features.
“The findings were a little surprising to me because, based on prior literature, I thought there would have been more of a clinical difference between the groups, particularly in the severity or with the endoscopic findings,” Evan S. Dellon, MD, MPH, director, Center for Esophageal Diseases & Swallowing at the University of North Carolina at Chapel Hill, told Medscape Medical News. “That was our hypothesis.”
Instead, Dellon and colleagues found that while vitamin D levels were lower in patients with EoE, deficiency was similar to those without EoE, and for the most part, there was no association between vitamin D levels and clinical or endoscopic features of EoE.
The study was published online in Digestive Diseases and Sciences.
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Further Investigation Warranted
Researchers performed a secondary analysis of a prospective cohort study that used data and biosamples from adults who underwent outpatient esophagogastroduodenoscopy. Before each procedure, blood was obtained. Serum 25-hydroxyvitamin D3 (25(OH)D3) was measured by enzyme-linked immunosorbent assay (ELISA). Vitamin D levels for patients with EoE and control participants were compared at baseline. Among patients with EoE, vitamin D levels also were compared for clinical, endoscopic, and histologic measures.
EoE cases were defined by consensus guidelines, with a diagnosis requiring ≥ 15 eosinophils per high-powered field in esophageal biopsy specimens in the setting of symptoms of esophageal dysfunction, and exclusion of other causes of esophageal eosinophilia.
Controls were patients who underwent upper endoscopy and biopsy for upper gastrointestinal symptoms such as dysphagia, chest pain, or heartburn but who were not diagnosed with EoE.
The analysis included 40 patients with EoE, with a mean age at diagnosis of 38.2 years; 63% were men, 93% were White, 63% were atopic, and 38% were taking vitamin D supplements at diagnosis.
The 40 control participants had a mean age at diagnosis of 50.9 years; 33% were men, 75% were White, 38% were atopic, and 30% were taking vitamin D supplements at diagnosis.
The percentage of previous diagnosis of vitamin D deficiency was 10% in the EoE group and 13% in the control group.
The analyses showed that the mean serum 25(OH)D3 level was slightly lower in patients with EoE than in control participants (30.9 ng/mL vs 35.9 ng/mL).
After controlling for age, sex, and race, adjusted 25(OH)D3 levels were 10.8 ng/mL lower in patients with EoE. However, 25(OH)D3 deficiency (< 20 ng/mL) was similar in patients with EoE and the control group (20% vs 15%).
Furthermore, levels of 25(OH)D3 were not associated with differences in clinical or endoscopic features of EoE. For example, among patients with EoE, vitamin D levels were similar between those with and without atopy and with and without strictures. Additionally, the EoE Endoscopic Reference Score and peak eosinophil counts did not significantly correlate with 25(OH)D3 levels.
Among the 11 EoE cases in which lamina propria could be assessed on biopsy (seven with fibrosis and four without), 25(OH)D3 levels were lower in those with fibrosis (23.2 ± 9.6 vs 45.0 ± 17.7).
“Though only a subset of cases had lamina propria tissue for evaluation, vitamin D is known to have a crucial role in developing pulmonary fibrosis due to various molecular mechanisms,” the authors wrote. “Therefore, development of EoE fibrosis in the setting of vitamin D deficiency warrants further investigation.”
“Overall, our findings suggest that vitamin D is likely not a risk factor that impacts clinical presentation, but given other emerging data, its role in modifying EoE treatment response should still be investigated,” the authors concluded.
Because lower vitamin D levels were found in some patients with EoE, it’s important for clinicians with patients undertaking an elimination diet to collaborate with a dietitian to decide whether to check routine nutrition labs before and during the intervention, Dellon told Medscape Medical News.
“Dairy is the most common food excluded when treating patients with EoE, and obviously, it’s also a really good source of vitamin D,” he added.
‘One Piece of the Puzzle’
In a related editorial, Milli Gupta, MD, of the University of Calgary in Canada, and Albert Bredenoord, PhD, of the Academic Medical Center, Amsterdam, the Netherlands, addressed potential roles for vitamin D in EoE, a chronic type 2 immune-mediated disorder.
Vitamin D deficiency is associated with a more severe disease state in other chronic type 2 inflammatory disorders, such as asthma, atopic dermatitis, and atopic rhinitis, and supplementation improves the overall disease, Gupta and Bredenoord wrote. Because of these conditions’ shared pathway for inflammation and epithelial barrier disruption, it could be assumed that a larger number of atopic diseases would be linked with greater likelihood of low vitamin D levels, they added.
Although the current study did not show an association between EoE with atopy and vitamin D levels, it would be interesting to follow patients who have atopic EoE and receive vitamin D supplementation to see if their disease severity improves, Gupta and Bredenoord wrote.
“Due to this linked pathophysiology, it may be reasonable to suggest patients with EoE take vitamin D as a means to reduce their potential risk of disease progression,” they added.
Although Dellon and colleagues did not find an association with clinical endpoints, “there is enough evidence of the impact of vitamin D on type 2 [inflammatory] disorders to implicate EoE by association,” Gupta and Bredenoord wrote. “Further research in combination with novel treatments may help answer how best to incorporate vitamin D.”
Dellon agreed. “This is an area that needs more investigation, particularly with increasing vitamin D deficiency and the increasing EoE numbers that we’re seeing. Diet is an important factor. So, I think this study is just one piece of the puzzle, and really an initial piece. There will be more research on this going forward.”
Dellon and colleagues declared no conflicts of interest. Gupta participates on advisory boards and receives speaker fees from Sanofi/Regeneron, AVIR Pharma, Bausch Health, Takeda, and Astra Zeneca. Bredenoord received research funding from Norgine, Dr. Falk Pharma, Thelial, Sanofi/Regeneron, and SST, and received speaker and/or consulting fees from Laborie, Medtronic, Bristol Myers Squibb, Dr. Falk Pharma, Reckitt, Aqilion, Eupraxia, Alimentiv, Sanofi/Regeneron, and AstraZeneca.
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