Systematic Review

The Association Between Eosinophilic Oesophagitis and Coeliac Disease

A. J. Lucendo; Á. Arias; J. M. Tenias

Disclosures

Aliment Pharmacol Ther. 2014;40(5):422-434. 

In This Article

Abstract and Introduction

Abstract

Background The relationship between eosinophilic oesophagitis (EoE) and coeliac disease (CD) remains controversial, with studies yielding varied results.

Aim To systematically review the evidence of a possible association between both diseases.

Methods Electronic searches were performed with keywords relating to EoE and CD in the MEDLINE, EMBASE and SCOPUS databases. Summary estimates were calculated. A random-effects model was used depending on heterogeneity (I 2). Publication bias was assessed with the aid of funnel plot analysis, along with the Begg–Mazumdar, Harbord and Egger tests.

Results The search yielded 197 references; 30 were included in the quantitative summary, with most of these presenting methodological inconsistencies. Significant publication bias in favour of short studies reporting positive associations between both diseases was documented. The prevalence of EoE in CD ranged from 0% to 10.7% (I 2 = 78.9%). Prevalence of CD in EoE varied between 0.16% and 57.1% (I 2 = 89%). One high-quality, prospective, randomly selected, population-based study documented a 1.1% prevalence of CD, with no patients presenting EoE. Clinical and methodological heterogeneity hindered the performance of quantitative summaries for prevalence data. A gluten-free diet was effective in achieving histological remission of EoE in 32.1% of coeliac patients (95% confidence interval, 14.9–52.2%; I 2 = 52.2%), which was similar to that expected for wheat elimination in EoE patients.

Conclusions While a lack of valid studies prevents us from completely ruling out a true association between EoE and CD, currently available evidence does not support this hypothesis. Indeed, the only epidemiological study with sufficient validity points to the independence of both diseases.

Introduction

Eosinophilic oesophagitis (EoE) and coeliac disease (CD) are distinct immunological entities affecting the upper gastrointestinal (GI) tract, both of which are triggered and maintained by exposure to food antigens, but with important differences in clinical and histopathological features.

Eosinophilic oesophagitis is an inflammatory disorder characterised by symptoms of oesophageal dysfunction and histological evidence of eosinophil-predominant inflammation in oesophageal mucosal biopsies, but with no involvement of distal GI segments. Diagnosis relies on the persistence of symptoms after the exclusion of other causes of oesophageal eosinophilia, especially gastro-oesophageal reflux disease.[1] EoE is frequently associated with atopic diseases such as bronchial asthma and rhinoconjunctivitis; in all three, a Th2-type immune response seems to be involved.[2] In fact, EoE is now recognised as a particular form of food allergy, after documented disease resolution was achieved through dietary modifications designed to reduce exposure to food antigens.[3,4]

For its part, CD is a chronic systemic disorder primarily affecting the GI tract, characterised by inflammatory changes in the small bowel that are triggered and maintained by a Th1-type immunological response provoked by exposure to gluten in the diet.[5] CD constitutes the main cause of malabsorption of nutrients in developed countries,[6] manifesting itself in genetically susceptible individuals and frequently leading to various associated disorders.[7] In fact, patients with CD are often susceptible to concomitant autoimmune diseases such as type 1 diabetes mellitus and autoimmune thyroiditis,[8] although their actual risk of developing other atopic diseases remains unclear.[9–12]

Up until 20 years ago, both diseases were considered to be of low prevalence. However, several recent epidemiological studies have clearly shown an increasing number of diagnosed cases in both children and adults. For example, a steady rise in diagnosed cases of CD has been observed over the past few years, with continuous growth in both incidence and prevalence rates over time[5,13,14] so that CD now constitutes a highly prevalent disease affecting between 1% and 3% of the European and US populations at some stage in life.[15] In those same populations, EoE is currently estimated to affect 1 of 1800 individuals,[16–18] constituting the second most common cause of oesophageal symptoms after gastro-oesophageal reflux disease (GERD) and being the main cause of dysphagia and food impaction in young patients.[19,20] It has also become clear that the increased incidence for both diseases cannot be exclusively attributed to better diagnostics or higher detection rates.[14,21]

In recent years, several case reports and cohort studies have suggested an association between EoE and CD. While this association was initially reported for paediatric patients,[22–26] it has since been reiterated in adult patients,[27] but not universally confirmed in large population-based studies.[28] Even though both diseases are caused by aberrant immune responses to ingested antigens and are potentially responsive to a food elimination diet, differences in the underlying pathophysiological mechanisms leading to each of them,[29,30] along with the absence of a genetic connection between EoE and CD, have prevented researchers from establishing a direct relationship. As a result, the elucidation of a true association between these disorders remains elusive.

The aim of this study was to evaluate, assess, and quantify the association between EoE and CD by conducting a systematic review of the literature on the relationship of the two disorders in both children and adults, including an evaluation of the efficacy of a gluten-free diet (GFD) in inducing EoE remission among coeliac patients.

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