Introduction

Endoscopy abnormalities of eosinophilic esophagitis (EoE) are currently graded based on the EoE endoscopic reference score (EREFS) ranging 0 to 9. Research has shown that esophageal biopsies are often omitted in Europe in patients reporting dysphagia when the upper endoscopy (EGD) shows no abnormalities [1]. However, a proportion of patients with eosinophilic esophagitis (EoE) may have normal endoscopy (i.e., EREFS=0), making the diagnosis more difficult and increasing the risk of diagnostic delay.

Aims & Methods

We investigated predictors of a diagnosis of EoE when the EGD is unremarkable (i.e., EREFS=0). Consecutive adult patients (≥18 years) with dysphagia who had EREFS=0 at an EGD with six esophageal biopsies were prospectively enrolled. All patients underwent EGD while off any eosinophil-depleting treatment. EoE with EREFS=0 was diagnosed based on the presence of at least 15 eosinophils/high-power field in at least one of six esophageal biopsies. When all six esophageal biopsies showed <15 eosinophils/high-power field, patients were diagnosed with non-EoE dysphagia (NED). Demographics, diagnostic delay (i.e., interval time between symptoms onset and diagnosis), esophageal symptoms, and atopic comorbidities (i.e., allergic rhinitis, asthma, eczema) were collected for all patients. Pearson's Chi-squared test and Fisher's exact test were used for comparisons. Odds ratios (ORs) were calculated to quantify associations between disease states. Significance threshold was set at p<0.05.

Results

Of 133 included patients, 51 (38%) had NED, while 82 (62%) had EoE with EREFS=0. Patients with EoE were more commonly males (67% vs 35%; p<0.001) and younger (37 vs 46 years; p=0.005) compared to patients with NED. Patients with EoE were diagnosed with a significantly longer diagnostic delay than NED (28 vs 4 months; p<0.001). Heartburn, regurgitation, chest pain and dyspepsia had similar prevalence in the two groups. In contrast, patients with EoE had a significantly higher prevalence of atopic comorbidities compared to NED (83% vs 39%; p<0.001).
The presence of rhinitis, diagnostic delay longer than 12 months, any atopic comorbidity, age younger than 37 years, and male sex were associated with an increased risk of EoE with OR of 47.0, 11.6, 7.4, 3.8, and 3.7, respectively (p<0.01 for all).

Conclusion

EoE remains a possible diagnosis in patients reporting dysphagia even when endoscopy is normal. The presence of rhinitis and longer diagnostic delay, the presence of any atopic comorbidity, and younger age are associated with a diagnosis of EoE and are helpful to raise the suspicion of EoE and prompt endoscopists to collect esophageal biopsies.

References

[1] Tourlamain, G., Garcia-Puig, R., Gutiérrez-Junquera, C., Papadopoulou, A., Roma, E., Kalach, N., Oudshoorn, J., Sokollik, C., Karolewska-Bochenek, K., Oliva, S., Strisciuglio, C., Bauraind, O., Auth, M. K., Thomson, M., Otte, S., Rok, O., Dias, J. A., Tzivinikos, C., Urbonas, V., Kostovski, A., … ESPGHAN EGID Working group (2020). Differences in Management of Eosinophilic Esophagitis in Europe: An Assessment of Current Practice. Journal of pediatric gastroenterology and nutrition, 71(1), 83–90. https://doi.org/10.1097/MPG.0000000000002672

Introduction

Eosinophilic oesophagitis (EoE) is a chronic, progressive type 2 inflammatory disease. Proton-pump inhibitors (PPIs), swallowed topical corticosteroids (STCs), and elimination diets have been used as standard treatments for EoE patients. However, the real-world evidence (RWE) highlighting disease burden in Europe are limited.

Aims & Methods

To assess disease burden and treatment patterns among adolescent and adult patients with EoE in real-world practice.
Medical records were retrospectively reviewed for patients (aged ≥12 years) who were newly diagnosed with EoE between 1 January 2009 and 31 December 2019 (index) in Germany, France, Spain, and the United Kingdom. Patients with a peak eosinophil (eos) count (PEC) of ≥15 eos/hpf within 90 days of the index date and ≥1 follow-up endoscopy within 24 months of the index date were included. Demographics, clinical features, treatment patterns, and health outcomes were assessed from the 12-month pre-index period to the last medical record entry or death. Disease progression was assessed via physician-defined (based on symptoms, endoscopy findings, histology, need for dilation, and food impaction) and proxy-reported outcomes (dilation performed, strictures, dysphagia, evidence of food impaction, treatment initiation in treatment-naïve patients and switching/augmentation).

Results

Overall, 385 patients were included, with 70.1%–78.1% being male; the mean age was 27.8 to 33.9 years. At EoE diagnosis, the PEC was 35.3–46.1 eos/hpf, the endoscopic appearance of the oesophagus was abnormal in 73.7%–85.6% of patients, and dysphagia was present in 59.8%–82.8% of patients. Most of the patients across all 4 countries were treated with PPIs (61.5%–91.8%), STCs (56.7%–82.3%) and elimination diets (41.4%–55.2%) after EoE diagnosis. Of the patients with available data, abnormal histology (≥15 eos/hpf) was reported in 44.8%–72.0% of patients during the first 5 years after EoE diagnosis. The abnormal endoscopic appearance of the oesophagus was observed in 34.6%–83.3% of patients after approximately 2 years of EoE diagnosis and dysphagia was present in 10.2%–25.0% of patients after 4 years of EoE diagnosis across all 4 countries. While physician-defined disease progression occurred in 6.1%–16.1% of patients, 19.4%–35.1% of patients experienced proxy-reported outcomes of potential disease progression (including oesophageal dilation performed in 10.8%–21.7% of patients) after EoE diagnosis. An overview of patient and clinical characteristics at EoE diagnosis and treatment patterns and disease progression (physician-defined and proxy-reported) after EoE diagnosis across Germany, France, Spain, and the United Kingdom is provided in the Table.

Conclusion

Adolescent and adult patients with EoE chronically experienced substantial disease burden. A subset demonstrated disease progression, perhaps underrecognised despite treatment with PPIs, STCs, and elimination diets. Hence, successful EoE management may include proactive disease monitoring, treating underlying pathophysiology and prescribing maintenance therapies to achieve long-term clinical remission.

References

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Disclosure

Ulrike von Arnim: Consulting and/or speaker fees from Dr. Falk Pharma, Sanofi, Astra Zeneca, EsoCap, Abbvie, Janssen, Takeda, Pfizer, Bristol Myers Squibb.
Frank Zerbib: Consulting and/or speaker fees from Sanofi, Dr Falk pharma, Bristol Myers Squibb, Bioprojet, AstraZeneca.
Tiffany Pela, Juby A. Jacob-Nara, Gaelle Le-Bagousse-Bego, Sarette T. Tilton: Employees of Sanofi; may hold stocks and/or stock options in the company.
Bram P. Raphael, Amr Radwan, Ryan B. Thomas: Employees of Regeneron Pharmaceuticals, Inc.; may hold stocks and/or stock options in the company.
Rohan C. Parikh, Fareedat Bello: Employees of RTI Health Solutions, which received research funding from Sanofi to design and execute this study.
Funding: This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.
Acknowledgement: Medical writing support was provided by Akshata Rao and Ali Nasir Siddiqui, PhD, of Sanofi.