Introduction

Eosinophilic esophagitis (EoE) presents with varying histologic extents, yet the impact of comorbidities on eosinophilic distribution and the implications on disease progression and treatment response remains poorly understood.^1,2 This study aimed to investigate the prevalence of different EoE extents and their impact on disease progression and treatment response within a multicenter cohort.

Aims & Methods

Clinical, endoscopic, and histologic data from adult EoE patients actively followed up at four Italian referral centers from October 2022 to October 2023 were retrospectively collected. The primary endpoint was to assess the prevalence of different EoE histologic extents (proximal, distal, diffuse) based on the presence of a pathological eosinophilic infiltrate (³15 Eo/HPF) and evaluate their association with comorbidities (atopic diseases, gastroesophageal reflux disease), clinical characteristics, endoscopic features. The secondary objective was to compare treatment responses among different histologic extents of EoE.

Results

149 patients were included (median age: 37 years [IQR 25-51], 38.2% males). Proximal EoE was observed in 8.1% (12/149), distal EoE in 27.5% (41/149), and diffuse EoE in 64.4% (96/149) of patients. In proximal-EoE, male patients were significantly more prevalent (91.7% vs. 68.3% distal-EoE vs. 55.5% diffuse-EoE, P=0.03). No significant differences were found in the rate of autoimmune comorbidities (8.3%, 14.6% distal-EoE, 10.4% diffuse-EoE; P=0.8). Only allergic rhinitis was significantly more prevalent in the distal and diffuse-EoE groups compared to the proximal group (33.3% vs. 72.5% vs. 61.5%, P=0.049). The prevalence of asthma, atopic dermatitis, oral allergy syndrome, and gastroesophageal reflux disease was similar among the three EoE extent groups. Endoscopic inflammatory features at diagnosis were significantly more prevalent in the proximal-EoE group, compared to the distal and diffuse-EoE groups (91.7% vs 53.8% vs 66%; P=0.05). Endoscopic fibrotic features at diagnosis were similar between all the groups (proximal-EoE 50%, distal 42.5%, and diffuse-EoE 51.1%; P=0.6) The clinical response after first-line therapy was comparable in all groups (75.0%, 70.7%, and 69.8%, P=0.93) and proton pump inhibitors were the most frequently prescribed therapy (77.8%). The endoscopic fibrotic remission rate after first-line therapy was higher in the proximal-EoE compared to the distal and diffuse-EoE groups (100.0% vs. 35.7% vs. 13.8%, P=0.0001).

Conclusion

In adult patients with EoE, an increasing proximal-to-distal gradient of esophageal eosinophilic infiltrate was observed. There was no clear correlation between the histologic extent of EoE and comorbidities, development of fibrosis, and response to treatment.

References

1. Ghoz H, Stancampiano FF, Valery JR, et al. Extent of eosinophilic esophagitis predicts response to treatment. Endosc Int Open 2021;9:E1234-e1242.
2. Godat A, Mueller R, Schenker D, et al. Eosinophil Distribution in Eosinophilic Esophagitis and its Impact on Disease Activity and Response to Treatment. Clin Gastroenterol Hepatol 2023.

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and a peak eosinophil count of >15 cells per high power field (HPF). Recent studies suggest that mast cells play a key role in its pathophysiology. This study investigates the presence of mast cells in different groups of patients with EoE.

Aims & Methods

Biopsy samples from patients newly diagnosed with EoE were analyzed, and the Eosinophilic Esophagitis Histology Scoring System (EOEHSS) grade and stage scores were calculated. Biopsy samples were divided in two groups: t0 (before the starting of EoE therapy) and t1 (after EoE therapy). Mast cells were detected using tryptase immunohistochemistry, and the maximum number of mast cells counted in a high-power field (PMC), was recorded. Univariate correlation analysis were performed between PMC and peak eosinophil count (PEC), PMC and EOEHSS grade, PMC and EOEHSS stage, PMC and EREFS.

Results

12 patients affected by EoE were divided in group 1, treated with PPIs [Esomeprazole 40 mg, bis in die (bid)] and group 2, treated with BOT (budesonide oral tablets 1 mg, bid). Univariate correlation analysis were performed at t0 and t1. Results from Pearson’s R for analysis at t0 are showed a positive linear correlation in PEC-PMC (0,567, p=0,043) and EOEHSS grade-PMC (0,559, p=0,047). At t1, EREFS-PMC had a positive correlation (0,726, p 0,005), like also EOEHSS grade-PMC (0,74, p=0,002) and EOEHSS stage-PMC (0,818, p<0,001).

Conclusion

PCM positively correlates with PEC, EOEHSS grade, EOEHSS stage and EREFS in untreated samples, supporting their role in EoE and type-2 inflammation. In treated cases, PMC correlate with PEC, EOEHSS grade, EREFS. A highly statistically significant strong positive linear correlation was found between PMC and EOEHSS stage, as the latter is more likely to reflect the whole esophageal histologic changes.
Our study suggests that mast cell count, alongside eosinophil counts, could be an important factor in evaluating anti-inflammatory therapeutic interventions and it may be a useful adjunct to existing endoscopic and histologic markers in assessing EoE severity, supporting their role in EoE and type-2 inflammation. To confirm these findings, further longitudinal prospective studies are required.

References

N. de Bortoli, P. Visaggi, R. Penagini et al., The 1st EoETALY consensus on the diagnosis and management of eosinophilic esophagitis – Definition, clinical presentation and diagnosis, Digestive and Liver Disease
Collins MH, et al. Eosinophilic esophagitis histology remission score: significant relations to measures of disease activity and symptoms. J. Pediatr. Gastroenterol. Nutr. 2020;70(5):598–603
Kanamori A, et al. Esophageal mast cells may be associated with the perception of symptoms in patients with eosinophilic esophagitis. Esophagus. 2023 Apr;20(2):333-341
Bolton SM, et al. Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis. Am J Gastroenterol. 2020 Feb;115(2):224-233.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, progressive, esophageal disease driven by type 2 inflammation. The Endoscopic Reference Score (EREFS) is a validated tool assessing 5 endoscopic features of EoE. In LIBERTY EoE TREET (NCT03633617), dupilumab improved histologic, symptomatic, and endoscopic features of EoE up to 52 weeks.

Aims & Methods

This analysis assessed the effect of dupilumab in adolescents and adults with EoE, according to their endoscopic profile at baseline. Patients with EoE aged ≥12 years were randomized 1:1 to 24 weeks of dupilumab 300 mg weekly (qw) or placebo in Parts A/B of LIBERTY EoE TREET. Eligible patients who completed Parts A/B entered Part C and received dupilumab 300 mg qw to Week (W)52. Patients were categorized according to their endoscopic profile at baseline: inflammatory ([edema or exudate or furrow] EREFS score ≥1 and [ring and stricture]=0) and mixed ([edema or exudate or furrow] ≥1 and [ring or stricture] ≥1) (patients with a fibrostenotic only profile were excluded due to small numbers). The proportion of patients achieving peak eosinophil count (PEC) ≤6 eosinophils per high-power field (eos/hpf), absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) score, EREFS total score, inflammatory (edema, exudate, furrow) and fibrostenotic (ring, stricture) subscores were assessed at W24 and W52. Patients from Parts A/B, and Parts A–C/B–C were pooled, respectively.

Results

Of 240 patients included, 32.9%/63.3% had an inflammatory/mixed endoscopic profile at baseline. Patients with a mixed profile were older than those with an inflammatory profile (mean 33.8 years [standard deviation 12.4] vs 20.7 [10.9], P<0.0001). At W24, the proportion of patients achieving PEC ≤6 eos/hpf was significantly higher with dupilumab vs placebo, regardless of endoscopic profile (inflammatory: 50.5% difference [95% confidence interval (CI) 32.1, 68.9]; mixed: 57.4% [44.8, 70.1]; both P<0.0001). Dupilumab also improved DSQ score vs placebo at W24, regardless of endoscopic profile (least squares mean difference [95% CI] −10.7 [−18.7, −2.7], P<0.01; −10.1 [−14.9, −5.3], P<0.0001). At W52, further improvements were observed in patients under continuous dupilumab; improvements were also reported in patients who switched from placebo to dupilumab at W24. Dupilumab treatment improved endoscopic features of EoE vs placebo at W24, as assessed by the EREFS total score and inflammatory subscore, regardless of endoscopic profile. EREFS fibrostenotic subscore improved in patients with evidence of fibrostenotic disease at baseline (mixed profile) vs placebo at W24.

Conclusion

Dupilumab 300 mg qw improved histologic, symptomatic, and endoscopic aspects of EoE at W24 vs placebo, with further improvements at W52, regardless of the patient’s esophageal endoscopic phenotype (inflammatory or mixed).

Disclosure

Savarino EV: AbbVie, Agave, Alfasigma, Biogen, Bristol Myers Squibb, Celltrion, Dr Falk, Eli Lilly, Fenix Pharma, Johnson & Johnson, JB Pharmaceuticals, Merck & Co, Nestlé, Pfizer, Reckitt Benckiser, Regeneron Pharmaceuticals Inc., Sanofi, SILA, Sofar, Takeda, Unifarco - consulting fees; AbbVie, Agave, AGPharma, Alfasigma, CaDiGroup, Celltrion, Dr. Falk, EG Stada Group, Fenix Pharma, Galapagos, Johnson & Johnson, JB Pharmaceuticals, Innovamedica/Adacyte, Eli Lilly, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco – speaker fees. Peterson K: AGA, Alladapt, Allakos, AstraZeneca, Bristol Myers Squibb, Ellodi, Invea, Lucid, Nexstone, Peerview, Regeneron Pharmaceuticals Inc., Takeda, WebMD – consultant. AGA, Allakos, Peerview, Regeneron Pharmaceuticals Inc., Takeda, WebMD – speaker fees. Allakos, Chobani – educational grants. Nexeos Bio – stock and optionsXia C, RaphaelBP, Radin, A: Regeneron Pharmaceuticals Inc. – employees and shareholders. Zaghloul S, Angello JT: Sanofi – employees, may hold stock and/or stock options in the company.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, type-2 inflammation-driven esophageal disease causing dysphagia and esophageal dysfunction. Patients with inflammatory bowel disease (IBD) or other type-2 inflammatory disorders may have an increased risk of EoE, but prevalence data are limited. This study examines the prevalence of dysphagia and EoE in patients with type-2 inflammatory diseases or IBD.

Aims & Methods

In this prospective, multicentric, questionnaire-based screening study, patients from the departments of gastroenterology, pulmonology, dermatology, and otolaryngology at the Medical University of Vienna, as well as from the Allergy Center Floridsdorf, were screened for dysphagia using the validated brief esophageal dysphagia questionnaire (BEDQ). The primary endpoint was the prevalence of clinically relevant dysphagia, defined as a BEDQ score ≥10 or a history of bolus impaction in the past year. Endoscopy was offered to symptomatic patients without recent biopsies. Patient characteristics and differences in absolute eosinophil count, eosinophilic cationic protein (ECP), and IgE levels were analyzed using independent-samples T-tests.

Results

A total of 690 patients (45.7% female, mean age 54.5 years) were screened; 54.4% had IBD, 20.2% allergic rhinitis, 16.4% asthma, 8.7% atopic dermatitis, 6.4% chronic rhinosinusitis with nasal polyps (CRSwNP), and 5.2% IgE-mediated food allergy with multiple diagnoses possible. Overall, 5.1% (n=35) exhibited clinically relevant dysphagia. EoE was previously diagnosed in 2.0% (n=14), including four patients with clinically relevant dysphagia. Among the remaining 31 patients, eight had prior endoscopies ruling out EoE, seven underwent endoscopy revealing two new EoE cases, and 16 are still awaiting gastroscopy. No significant differences in IgE, eosinophilic count, or ECP were found between patients with EoE, those with dysphagia, and asymptomatic individuals.

Conclusion

Patients with IBD and type-2 inflammatory diseases exhibit a high prevalence of dysphagia. While EoE is more common than in the general population, most dysphagia remains unexplained. Systematic dysphagia screening in this high-risk population may reduce diagnostic delay.