Interactions between gastro-oesophageal reflux disease and eosinophilic oesophagitis

doi:10.1016/j.bpg.2015.06.009

Best Practice & Research Clinical Gastroenterology

Volume 29, Issue 5, October 2015, Pages 749-758

https://doi.org/10.1016/j.bpg.2015.06.009 Get rights and content

Abstract

Gastro-oesophageal reflux disease (GORD) is the most common oesophageal disorder, whereas eosinophilic oesophagitis (EoE) is an emerging disease unresponsive to PPI therapy. Updated guidelines in 2011 described proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE), a novel phenotype in EoE patients who were responsive to PPIs. This article aims to update the complex interplay between GORD, EoE and PPIs. Oesophageal mucosal integrity is diffusely impaired in EoE and PPI-REE patients. PPI-REE might occur with either normal or pathological pH monitoring. The genetic hallmark of EoE is overlapped in PPI-REE, but not in GORD. PPIs can partially restore epithelial integrity and reverse allergic inflammation gene expression in PPI-REE. Acid hypersensitivity in EoE patients may explain symptomatic but not histological response on PPIs. Unsolved issues with PPI-REE are whether oesophageal barrier impairment is the cause or the effect of oesophageal eosinophilia and whether PPIs primarily targets barrier integrity or oesophageal inflammation.

Section snippets

GORD, EoE and PPI-REE: who is who?

Updated similarities and differences between GORD, EoE and PPI-REE are summarized in Table 2.

GORD is a chronic condition that develops when the reflux of stomach contents, normally acid, causes troublesome symptoms and/or complications. The most common symptoms of GORD are heartburn and regurgitation, and to a lesser extent, dysphagia [23]. It mainly involves distal oesophagus and promotes a Th1 inflammatory response, with over expression of interleukin (IL)-8, monocyte chemoattractant protein

How do we define GORD in a patient with oesophageal eosinophilia?

GORD is one of the most common gastrointestinal disorders, affecting 10–20% of western population, typically males in their second to fifth decade of life. A presumptive diagnosis of GORD can be established upon typical symptoms (heartburn and regurgitation) and empirical PPI therapy can be prescribed accordingly [41]. Pathological oesophageal acid exposure, measured by pH monitoring, can be detected in 80% of patients with erosive GORD (ie, reflux oesophagitis) and 50% with non-erosive GORD

Interplay between GORD, EoE and PPI therapy

Of note, EoE adult patients are usually young males as well (3:1 ratio), so both diseases can largely coexist, with GORD in up to 30%–50% of EoE patients [20]. As such, coexistence of both disorders might occur within several clinical scenarios: 1) Both diseases coexist but unrelated; 2) GORD contributes to or causes EoE; 3) EoE contributes to or causes GORD [13]. The potential mechanisms whereby both disorders can interact are summarized in Table 3, as well as rationale basis for PPI therapy

Summary

GORD is the most common oesophageal disorder, usually responsive to PPI therapy, whereas EoE is an emerging disease unresponsive to PPI therapy. GORD and EoE were rigidly separated in 2007 guidelines according to oesophageal pH monitoring or response to PPI therapy. Updated guidelines in 2011 described a novel phenotype, proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE), referring to patients who appear to have EoE clinically, but who achieve complete remission after PPI

Conflict of interest

None.

Funding source

None.

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Treatment with high-dose proton pump inhibitors helps distinguish eosinophilic esophagitis from noneosinophilic esophagitis

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Cited by (21)

Endoscopic and histological characteristics in patients with eosinophilic esophagitis responsive and non-responsive to proton pump inhibitors
2020, Jornal de Pediatria
Citation Excerpt :
However, the correlation between eosinophilic infiltration of the esophagus with EoE and GERD was shown to be much more complex. Therefore, a third diagnostic category named PPI-responsive eosinophilic esophagitis (PPIREoE) was created, referring to the subgroup of patients with typical symptoms of EoE, but without GERD and with clinical and histological improvement after treatment with PPIs.10,11 Additionally, EoE and GERD can coexist in the same patient.
To compare endoscopic and histologic features of pediatric patients with eosinophilic esophagitis (EoE) responding to proton pump inhibitor (PPI) to those not responding to PPI.
Endoscopic reports and photographs of patients with symptoms of esophageal dysfunction and ≥15 eosinophils per high-powered field (eos/hpf) in esophageal biopsies prior to PPI trial were reviewed. Patients were classified as responsive to PPI (PPIREoE) or non-responsive to PPI (PPINREoE) according to response totreatment (<15 eos/hpf) at second endoscopy after 8 weeks.
Of the 231 patients (72.3% male), 64 (27.7%) were responsive to the proton pump inhibitors. Edema (77.3% vs. 62.5%, p = 0.031) and vertical lines (69.5% vs. 51.6%, p = 0.014) were more frequent in PPINREoE patients. An eosinophil count in the mid-esophagus ≥ 35 eos/HPF (25.1% vs. 12.5%) was more frequent in these patients (p = 0.001). Those with eosinophil count < 15 eos/HPF in the mid-esophagus at the first endoscopy were more likely to respond to treatment with proton pump inhibitors compared to patients with 15-34 eos/HPF (p = 0.004, OR: 3.26, 95% CI: 1.46-7.24) and to patients with ≥ 35 eos/HPF (p = 0.006, OR: 3.20, 95% CI: 1.39-7.41).
Edema and vertical lines at the endoscopy and a higher eosinophil count in the mid-esophagus were more frequent in patients who were non-responsive to proton pump inhibitors. As there were no significant differences in the other findings between the groups, it cannot be affirmed that these characteristics are sufficient to differentiate between PPINREoE and PPIREoE patients.
Comparar características endoscópicas e histológicas entre pacientes com esofagite eosinofílica responsiva (EoERIBP) e não responsiva (EoENRIBP) ao tratamento com inibidores de bomba de prótons.
Avaliados laudos e imagens endoscópicas de pacientes com sintomas de disfunção esofágica associados a contagem ≥15 eosinófilos por campo de grande aumento (eos/CGA) em biópsia do esôfago. Os pacientes foram classificados em responsivos (EoERIBP) ou não responsivos (EoENRIBP) aos inibidores de bomba de prótons conforme resposta ao tratamento na segunda endoscopia (<15 eos/CGA) após 8 semanas.
Dos 231 pacientes (72,3% masculino), 64 (27,7%) foram responsivos aos inibidores de bomba de prótons. Edema (77,3% vs. 62,5%, p = 0,031) e linhas verticais (69,5% vs. 51,6%, p = 0,014) foram mais frequentes nos EoENRIBP. A contagem de eosinófilos em esôfago médio ≥35 eos/CGA (25,1% vs. 12,5%) foi mais frequente nesses pacientes (p = 0,001). Os que apresentaram contagem de eosinófilos <15 eos/CGA no esôfago médio à primeira endoscopia apresentaram maior chance de responder ao tratamento com inibidores de bomba de prótons em comparação aos pacientes com 15-34 eos/CGA (p = 0,004; OR: 3,26; IC95%: 1,46 - 7,24) e aos pacientes com ≥35 eos/CGA (p = 0,006; OR: 3,20; IC95%: 1,39 - 7,41).
Edema e linhas verticais à endoscopia e maior contagem de eosinófilos em esôfago médio foram mais frequentes nos pacientes não responsivos aos inibidores de bomba de prótons. Uma vez que não houve diferenças significativas nos outros achados entre os grupos, não se pode afirmar que essas características sejam suficientes para distinguir pacientes com EoENRIBP dos pacientes com EoERIBP.
How to improve the diagnosis of eosinophilic esophagitis: Experience from a case series in Mexico
2017, Revista de Gastroenterologia de Mexico
La esofagitis eosinofílica (EEo) es un padecimiento crónico e inmunológico mediado por antígenos habitualmente alimentarios. Comparte síntomas inespecíficos con la enfermedad por reflujo gastroesofágico (ERGE). En México es rara vez reportada, tal vez por las características raciales de la población o por una sospecha diagnóstica insuficiente.
Describir una cohorte mexicana con EEo. Evaluar la utilidad de la historia clínica y de la endoscopia para diagnosticar EEo al compararla con ERGE.
Estudio retrospectivo de las características clínicas, hallazgos por endoscopia e histopatología de pacientes con EEo. Se realizó además un estudio de casos y controles con ERGE. Las imágenes obtenidas por endoscopia fueron interpretadas de forma ciega y aleatorizada por 4 gastroenterólogos, antes y después de otorgarles información sobre las alteraciones características de la EEo. Las biopsias esofágicas también fueron cegadas a 2 patólogos para evaluar su correlación diagnóstica. El análisis estadístico fue elaborado por pruebas exacta de Fisher y U de Mann-Whitney.
Se incluyeron 14 pacientes con EEo, 10 (71%) del sexo masculino de 35 años en promedio. En el grupo de EEo hubo más sujetos con historia personal de asma (p = 0.0023) e impactación alimentaria (p = 0.04). La evaluación inicial de los hallazgos endoscópicos mostró el 53% de interpretaciones acertadas para EEo incrementando al 96% en la segunda revisión (sensibilidad 100%, especificidad 71%, VPP 65%, VPN 100%).
Los pacientes con EEo en México tienen características similares a los de series occidentales. La sospecha clínica incrementa el diagnóstico por endoscopia hasta en un 40% cuando se mejora el conocimiento acerca de la enfermedad.
Eosinophilic esophagitis (EoE) is a chronic, immune disorder mediated largely by food antigens. It shares nonspecific symptoms with gastroesophageal reflux disease (GERD). EoE is rarely reported in Mexico, perhaps due to the racial characteristics of the population or because of insufficient diagnostic suspicion.
Our aim was to describe a Mexican cohort with EoE and evaluate the usefulness of the clinical history and endoscopy in the EoE diagnosis, in comparison with GERD patients.
A retrospective study was carried out on the clinical characteristics and endoscopic and histopathologic findings in patients with EoE, along with a case-control study on patients with GERD. The endoscopic images obtained were interpreted in a blind and randomized manner by 4 gastroenterologists, before and after providing them with information on the characteristic alterations of EoE. The esophageal biopsies were also blinded to 2 pathologists that evaluated their diagnostic correlation. The Fisher's exact test and Mann-Whitney U test were used in the statistical analysis.
Fourteen patients with EoE were included in the study. Ten (71%) of them were men and the mean age of the patients was 35 years. There were more subjects with a personal history of asthma (p = 0.0023) and food impaction (p = 0.04) in the EoE group. The initial evaluation of the endoscopic findings showed 53% correct EoE interpretations and rose to 96% in the second revision (sensitivity 100%, specificity 71%, PPV 65%, NPV 100%).
Mexican patients with EoE have similar characteristics to those of patients in western case series. Clinical awareness of the disorder increases endoscopic diagnosis in up to 40% of cases.
Mechanisms and clinical management of eosinophilic oesophagitis: an overview
2023, Nature Reviews Gastroenterology and Hepatology
Clinical Manifestations of Eosinophilic Esophagitis in Children and Adolescents: A Single-Center, Matched Case-Control Study
2020, Pediatric Gastroenterology, Hepatology and Nutrition
Pharmacological treatments for eosinophilic esophagitis: current options and emerging therapies
2020, Expert Review of Clinical Immunology
Clinical translational application of Raman spectroscopy to advance Benchside biochemical characterization to bedside diagnosis of esophageal diseases
2019, Journal of Gastroenterology and Hepatology (Australia)

View all citing articles on Scopus

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6Interactions between gastro-oesophageal reflux disease and eosinophilic oesophagitis

Abstract

Section snippets

GORD, EoE and PPI-REE: who is who?

How do we define GORD in a patient with oesophageal eosinophilia?

Interplay between GORD, EoE and PPI therapy

Summary

Conflict of interest

Funding source

Gastroenterology

J Pediatr Surg

Gastroenterology

Gastroenterology

J Pediatr

Clin Gastroenterol Hepatol

Gastroenterology

Gastroenterology

Mod Pathol

Hum Pathol

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

Gastrointest Endosc

Ann Allergy Asthma Immunol

Mucosal Immunol

Gastroenterology

Eosinophilic esophagitis

AJR Am J Roentgenol

Eosinophilic esophagitis, a rare manifestation of eosinophilic gastroenteritis

Schweiz Med Wochenschr

Esophageal involvement in eosinophilic gastroenteritis

Pediatr Radiol

Intraepithelial eosinophils in endoscopic biopsies of adults with reflux esophagitis

Am J Surg Pathol

Clinical and laboratory correlates of esophagitis in young children

J Pediatr Gastroenterol Nutr

Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome

Dig Dis Sci

Idiopathic eosinophilic esophagitis: a frequently overlooked disease with typical clinical aspects and discrete endoscopic findings [in German with English abstract]

Schweiz Med Wochenschr

Eosinophils in the oesophagus: peptic or allergic eosinophilic esophagitis? Case series of three patients with oesophageal eosinophilia

Am J Gastroenterol

Thoughts on the complex relationship between gastroesophageal reflux disease and eosinophilic esophagitis

Am J Gastroenterol

High intraepithelial eosinophil counts in oesophageal squamous epithelium are not specific for eosinophilic esophagitis in adults

Am J Gastroenterol

Treatment with high-dose proton pump inhibitors helps distinguish eosinophilic esophagitis from noneosinophilic esophagitis

J Pediatr Gastroenterol Nutr

Comparison of esomeprazole to aerosolized, swallowed fluticasone for eosinophilic esophagitis

Dig Dis Sci

Eosinophilic esophagitis: updated consensus recommendations for children and adults

J Allerg Clin Immunol

6
Interactions between gastro-oesophageal reflux disease and eosinophilic oesophagitis