Vitamin D Levels as a Potential Modifier of Eosinophilic Esophagitis Severity in Adults.

BACKGROUND: Vitamin D deficiency is associated with atopic and immune-mediated diseases but has not been extensively assessed in eosinophilic esophagitis (EoE). We aimed to assess if vitamin D levels in newly diagnosed EoE patients were lower than in non-EoE controls and examine levels in relation to EoE clinical features. METHODS: This secondary analysis of a prospective cohort study used data and biosamples from adults who underwent outpatient esophagogastroduodenoscopy. Before each procedure, blood was obtained and stored at -80oC. Serum 25-hydroxy-vitamin D3 (25(OH)D3) was measured by ELISA. Levels for cases and controls were compared at baseline. Within cases, 25(OH)D3 levels were compared for clinical, endoscopic, and histologic measures. RESULTS: We analyzed 40 EoE and 40 non-EoE controls. Mean serum 25(OH)D3 level was slightly lower in EoE patients than controls (30.9 ± 15.3 ng/mL vs. 35.9 ± 15.4; p = 0.15). After controlling for age, sex, and race, adjusted levels were 10.8 ng/mL lower in EoE patients (95% CI: -19.0, -2.5), but 25(OH)D3 deficiency (< 20ng/mL) was similar in cases and controls (20% vs. 15%; p = 0.56). Levels of 25(OH)D3 were not associated with differences in clinical or endoscopic features of EoE, and EREFS and eosinophil counts did not significantly correlate with 25(OH)D3 levels (R of -0.28 [p = 0.08] and - 0.01 [p = 0.93], respectively). 25(OH)D3 levels were lower in EoE cases with lamina propria fibrosis (23.2 ± 9.6 vs. 45.0 ± 17.7; p = 0.03). CONCLUSIONS: After adjusting for age, sex, and race, 25(OH)D3 levels were lower in EoE cases than controls, but deficiency was not common. 25(OH)D3 levels were generally similar across most EoE disease features.

Increasing Age at the Time of Diagnosis and Evolving Phenotypes of Eosinophilic Esophagitis Over 20 Years.

BACKGROUND: The presentation of eosinophilic esophagitis (EoE) is heterogeneous, but trends over time are not known. AIM: To determine whether clinical and endoscopic phenotypes at EoE diagnosis have changed over the past 2 decades. METHODS: In this retrospective cohort study, adults and children with newly diagnosed EoE were phenotyped as follows: (1) inflammatory vs fibrostenotic vs mixed on endoscopy; (2) atopic vs non-atopic; (3) age at symptom onset; (4) age at diagnosis; (5) presence of autoimmune or connective tissue disease; and (6) responsive to steroids. The prevalence of different phenotypes was categorized by 5-year intervals. Multivariate analysis was performed to assess for changes in patient features over time. RESULTS: Of 1187 EoE patients, age at diagnosis increased over time (from 22.0 years in 2002-2006 to 31.8 years in 2017-2021; p < 0.001) as did the frequency of dysphagia (67% to 92%; p < 0.001). Endoscopic phenotypes were increasingly mixed (26% vs 68%; p < 0.001) and an increasing proportion of patients had later onset of EoE. However, there were no significant trends for concomitant autoimmune/connective tissue disease or steroid responder phenotypes. On multivariate analysis, after accounting for age, dysphagia, and food impaction, the increase in the mixed endoscopic phenotype persisted (aOR 1.51 per each 5-year interval, 95% CI 1.31-1.73). CONCLUSION: EoE phenotypes have changed over the past two decades, with increasing age at diagnosis and age at symptom onset. The mixed endoscopic phenotype also increased, even after controlling for age and symptomatology. Whether this reflects changes in provider recognition or disease pathophysiology is yet to be elucidated.

Feeding Tube Placement, Complications, and Treatment Responses in a Large Eosinophilic Esophagitis Patient Population.

OBJECTIVES: Feeding tubes can provide a temporary or long-term solution for nutritional therapy. Little is known regarding the use of feeding tubes in patients with eosinophilic esophagitis (EoE). We sought to describe the characteristics and outcomes in EoE patients requiring tube feeding. METHODS: This was a retrospective cohort study of EoE patients at a large tertiary care health system. Demographics, clinical characteristics, and endoscopic findings were extracted from medical records, and patients who had a feeding tube were identified. Patients with and without a feeding tube were compared. Details about the tube, complications, and treatment were extracted. Growth, global symptomatic, endoscopic, and histopathologic (<15 eos/hpf) responses were compared before and after the initiation of feeding tube therapy. RESULTS: We identified 39 of 1216 EoE patients who had a feeding tube (3%). Feeding tube patients were younger (mean age 6.3 years), reported more vomiting, and had a lower total endoscopic reference score than non-feeding tube patients ( P < 0.01 for all). Tubes were used for therapy for an average of 6.8 years, with most patients (95%) receiving both pharmacologic and formula treatment for EoE. An emergency department visit for a tube complication was required in 26%. Tube feeding improved body mass index z score ( P < 0.01), symptomatic response (42%), endoscopic response (53%), and histologic response (71%). CONCLUSIONS: Among EoE patients, only a small subset required a feeding tube and predominantly were young children with failure to thrive. Feeding tubes significantly improved growth and, when used in combination with other treatments, led to reduced esophageal eosinophilic inflammation.

Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: a multicentre, randomised, double-blind, placebo-controlled clinical trial.

OBJECTIVE: We aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE). METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6). RESULTS: Of 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4±18.1 with mepolizumab and 8.3±18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113±77 to 36±43) than placebo (146±94 to 160±133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and ≤6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3±18.1 points for mepo/mepo and 18.6±19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions. CONCLUSIONS: Mepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement. TRIAL REGISTRATION NUMBER: NCT03656380.