EoE Concept And Epidemiology

Introduction

Eosinophilic esophagitis (EoE) is an inflammatory condition of the esophagus that, today, constitutes the most prevalent cause of chronic esophagitis after gastroesophageal reflux disease (GERD) and the leading cause of dysphagia and food impaction in children and young adults.

EoE

EoE represents a chronic, local immune-mediated esophageal disease, characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Other systemic and local causes of esophageal eosinophilia should be excluded. Clinical manifestations or pathologic data should not be interpreted in isolation.

Adult patients achieving clinical and histological remission on PPI therapy are part of the EoE continuum, rather than a separate entity. Responders and non-responders to PPI therapy show overlapping phenotypic, genetic, and mechanistic features. More data are required in children.

EoE and GERD are different entities and may coexist, either unrelated or interacting bidirectionally.

The incidence of EoE has increased and currently varies widely from 1 to 20 new cases per 100,000 inhabitants per year (mean value 7). Prevalence rates ranges between 13 and 49 cases per 100,000 inhabitants.

The frequency of EoE in adults with esophageal symptoms undergoing an upper endoscopy is 7%. This frequency may rise up to 23% and 50% in patients with dysphagia and food impaction, respectively. Further data in children are required.

EoE may occur at any age with a rising incidence in children with age and a peak in adults at 30–50 yrs.

Male gender is a strong risk factor for EoE both in children and adults.

Rhinitis, asthma and eczema are significantly more common in EoE patients compared to the general population. However, it remains unproven that atopy predisposes to EoE.

EoE is a distinct form of food allergy. IgE-mediated food allergies are common in EoE patients.

EoE and celiac disease are independent disorders.

EoE appears to have no causal or temporal relationship with hypereosinophilic syndromes, inflammatory bowel disease, esophageal atresia, and connective tissue disorders.

Diagnosis

In older children and adults with EoE solid food dysphagia, food impaction, and non-swallowing associated chest pain are the most commonly reported symptoms. In younger children and infants the most common symptoms reported are reflux-like symptoms, vomiting, abdominal pain, food refusal and failure to thrive.

At least six biopsies should be taken from different locations, focusing on areas with endoscopic mucosal abnormalities.

The accepted threshold for eosinophil density for the diagnosis of EoE is 15 eosinophils per high power field (standard size of ∼0.3 mm2) in esophageal mucosa, taken as the peak concentration in the specimens examined.

Hematoxylin-eosin staining is sufficient for histological assessment of EoE in routine clinical practice.

Besides peak eosinophil count, additional histological features may include eosinophil microabscesses, basal zone hyperplasia, dilated intercellular spaces, eosinophil surface layering, papillary elongation, and lamina propria fibrosis.

Currently, noninvasive biomarkers are not accurate to diagnose or monitor EoE. Some minimal invasive diagnostic tools show promise and merit further evaluation.

Symptoms do not correlate accurately with histologic disease activity, so histology currently continues to be necessary to monitor the disease.

Endoscopic findings alone do not reliably establish a diagnosis of EoE. Their value to assess disease activity needs further evaluation.

Natural history

Untreated EoE is usually associated with persistent symptoms and inflammation, leading to esophageal remodeling resulting in stricture formation and functional abnormalities. There is some evidence that effective anti-inflammatory treatment may limit progression.

EoE significantly impacts health-related quality of life of patients, impairing their social and psychological functioning.

There is no evidence so far that EoE is a pre-malignant condition.

Treatment

PPI therapy induces clinical and histological remission in a proportion of pediatric and adult patients with EoE.

In PPI responders, long-term PPI therapy is effective in maintaining remission.

Systemic steroids are not recommended in EoE.

Topical corticosteroids are effective for induction of histological remission in both pediatric and adult EoE patients.

In steroids responsive patients, long-term therapy with topical corticosteroids is effective in maintaining remission in a proportion of patients.

Swallowed topical corticosteroids seem to have a favorable safety profile in the treatment of EoE, with no serious side effects reported. Esophageal candidiasis, mostly incidental, may occur in up to 10% of patients.

There is a limited place for elemental diet in EoE, which should only be considered after failure of properly performed medical treatment and/or elimination diet. Elemental diet induces histologic remission in up to 90% of pediatric and adult EoE patients. There is limited information regarding symptoms.

Food allergy testing-based elimination diet induces histologic remission in less than one third of adult patients. This rate may be higher in pediatric patients.

The utility of allergy tests in the identification of food triggers of EoE is consistently low in adults and variable in children.

An empiric six-food group elimination diet induces histologic remission in around three quarters of pediatric and adult patients.

In adult patients, an empiric four-food elimination diet achieves remission in half of the patients, whereas a two-food elimination diet (animal milk and gluten-containing cereals) may be still effective in 40% of patients.

Prolonged avoidance of triggering foods may lead to drug-free sustained clinical and histological remission of EoE.

Endoscopic dilation improves dysphagia in up to three quarters of adult EoE patients with reduced esophageal caliber, without having an effect on the underlying esophageal inflammation.

Endoscopic dilation in EoE is a safe procedure, with a risk of esophageal perforation smaller than 1%.

PPIs, diet or topical steroids might be offered as first line anti-inflammatory therapy. The choice of therapy should be individually discussed with the patient and might be potentially interchangeable over time. The efficacy of any therapy should be checked by a follow-up endoscopy after a 6- to 12-week initial course. Endoscopic dilation should be considered in patients with dysphagia/food impaction unresponsive to anti-inflammatory treatment.

Azathioprine and 6-mercaptopurin might play a role in inducing and maintaining long-term remission in EoE in limited cases.

Sodium cromoglicate and antihistamines have no effect on symptoms or esophageal eosinophilia.

There is insufficient evidence to recommend montelukast, a leukotriene receptor antagonist, in patients with EoE.

First generation chemoattractant receptor- homologous molecule on Th2 cells (CRTH2) antagonists induces modest clinic and histologic improvement in EoE.

The anti-IL5 antibodies mepolizumab and reslizumab have no effect on symptoms and modestly reduce esophageal eosinophilia.

QAX576, an anti-IL13 antibody, has no effect on symptoms but reduces esophageal eosinophilia and downregulates EoE transcripts in a sustained manner.

Omalizumab, an anti-IgE antibody, has no effect on symptoms or esophageal eosinophilia.

Infliximab, an anti-tumor necrosis factor alpha antibody, has no effect on symptoms or esophageal eosinophilia.

                                    By: Dr.Arun Aggarwal Gastroenterologist