Eosinophilic Esophagitis (EoE)

How to Cite This Chapter: Collins A, Armstrong D, Horvath A, Bartuzi Z. Eosinophilic Esophagitis (EoE). McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.4.67. Accessed May 24, 2024.
Last Updated: July 25, 2019
Last Reviewed: September 19, 2019
Chapter Information

Definition, Etiology, PathogenesisTop

Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal disease affecting up to 1 in 2000 people in Europe and North America and, nowadays, the second most common esophageal disease, after gastroesophageal reflux disease (GERD). It occurs in all age groups but is more prevalent in White men from childhood to midlife. Clinically, EoE is characterized by symptoms of esophageal dysfunction and histologically, by eosinophil-predominant esophageal inflammation. EoE is distinct from other systemic and local causes of esophageal eosinophilia and from GERD, although EoE and GERD may coexist.

In many patients EoE is associated with concomitant atopic diseases, such as asthma, allergic rhinitis, and atopic dermatitis. In EoE food and environmental antigens stimulate a Th2 inflammatory response, which leads to the production of eotaxin-3, a potent chemokine that recruits eosinophils to the esophageal mucosa. Activated eosinophils secrete proinflammatory and profibrotic mediators, causing tissue damage and with time also fibrosis and remodeling that may ultimately progress to esophageal dysmotility and stricture.

Although EoE is considered to be an immune-mediated disease, the underlying pathogenetic mechanisms remain unclear. Whilst the therapeutic response to glucocorticoids and elimination diets in many patients is consistent with EoE being an immune-mediated disease, the improvement produced by proton pump inhibitors (PPIs) suggests that there may be other, non–immune-mediated mechanisms at play in some patients who have esophageal eosinophilia. When PPI-responsive esophageal eosinophilia (PPI-REE) was first reported, it was thought to be different from EoE. Now it appears that this condition is comparable to EoE and distinct from GERD with respect to clinical, pathologic, and genetic features of EoE. As a result, PPI-REE is no longer considered to be a separate diagnostic entity, distinct from EoE.

Clinical FeaturesTop

There are no specific symptoms diagnostic of EoE. In young children, the most common symptoms are vomiting, abdominal pain, feeding difficulties, refusal of food, and failure to thrive. In older children and adults, dysphagia, food impaction, GERD-like symptoms, and chest pain predominate; in this age group, EoE is now the most common cause of dysphagia and food bolus impaction. Assessment of symptom severity is hampered by patients’ attempts to minimize symptoms by avoiding foods that are difficult to swallow, chewing their food for prolonged periods, and drinking more fluids when eating.


Diagnostic Tests

In patients with clinical features consistent with EoE, diagnosis is based on upper endoscopy and esophageal biopsies confirming esophageal eosinophilia. Currently, there are no noninvasive tests that are sufficiently accurate to diagnose EoE or evaluate response to therapy. Absolute serum eosinophil counts correlate with the degree of esophageal eosinophilia at baseline and after glucocorticoid therapy but their diagnostic accuracy is insufficient for use in clinical practice. Similarly, other biomarkers associated with EoE pathogenesis have proved inadequate, alone or in combination, for diagnosis or disease monitoring.

1. Endoscopy: The 5 key endoscopic features of EoE are highlighted in the endoscopic reference score, a standardized tool which uses the acronym EREFS to grade the severity of exudates (whitish plaques), rings (trachealization), edema (loss of vascular pattern), furrows (longitudinal markings), and strictures. However, these features have only modest accuracy for the diagnosis of EoE and the esophageal mucosa may be normal in ~10% of adult patients. A diagnosis of EoE must therefore be confirmed by histology; because inflammation is variable, ≥6 biopsies should be taken from 2 different sites in the esophagus and, in particular, from areas that are endoscopically abnormal. Gastric and duodenal biopsies should also be taken at the initial diagnostic endoscopy to exclude eosinophilic gastroenteritis and other conditions.

2. Histology: Histologic assessment, using hematoxylin-eosin (HE) staining, identifies typical EoE features including eosinophils in the epithelium and other layers of the esophageal wall, eosinophilic clusters (microabscesses), dilated intercellular spaces, basal cell hyperplasia, expansion of the papillae, and fibrosis of the lamina propria. However, apart from esophageal eosinophilia and microabscesses, the other histologic features are not specific for EoE; furthermore, low-grade esophageal eosinophilia also occurs in GERD (usually <5 eosinophils per high power field [HPF]). The histologic diagnostic criterion is the finding of >15 eosinophils per HPF (~60 eosinophils/mm2), which has a sensitivity of 100% and a specificity of 96% for the diagnosis of EoE.

3. Contrast radiography: Barium esophagography may occasionally be helpful to evaluate dysphagia, because EoE strictures, when present, tend to be longer and more tapered than the localized distal strictures associated with GERD (as such, they can be missed at endoscopy).

4. Allergy testing: Skin prick tests to evaluate mast cell–bound IgE in the context of immediate allergic reactions and atopy patch tests to evaluate non-IgE cell-mediated reactions to potential food triggers of EoE have shown consistently low utility in adults and variable utility in children, with a poor positive predictive value (on average <50%) and only moderate to good negative predictive value (40%-90%). Elimination diets based on skin allergy testing lead to histologic remission in less than a third of adult EoE patients. Skin allergy tests are therefore not sufficiently accurate for use in clinical practice to determine food elimination or reintroduction strategies for EoE patients.

Diagnostic Criteria

The most recent consensus publication states that a diagnosis of EoE requires all 3 of:

1) Symptoms of esophageal dysfunction.

2) Esophageal biopsy findings of >15 eosinophils per HPF (~60 eosinophils/mm2).

3) Exclusion of non-EoE disorders associated with esophageal eosinophilia (causes of esophageal eosinophilia other than EoE and GERD; see below).

The efficacy of PPIs in reducing esophageal eosinophilia and EoE symptoms, limited correlation between esophageal acid exposure and PPI response, clinical and pathophysiologic similarities between PPI-responders and nonresponders, and coexistence of EoE and GERD as distinct conditions in the same patient have all recently led to the consensus recommendation that a trial of PPI therapy is no longer required to fulfill the diagnosis of EoE and recognition that a diagnosis of EoE cannot be excluded definitively in patients by normal biopsy results if they are taking PPIs at their initial endoscopy.

Differential Diagnosis

There are many diagnoses that should be considered in a patient with features of EoE, the most common being GERD. There are several epidemiologic and clinicopathologic features that differ between EoE and GERD (Table 1), but currently there is no single test that can reliably distinguish between these two conditions. A definitive diagnosis may be difficult, as EoE and GERD may occur concurrently in the same patient.

The differential diagnosis for EoE includes other causes of symptoms, such as dysphagia and chest pain, and other causes of esophageal eosinophilia (Table 2).


The mainstays of treatment are elimination diets, PPIs, or topical glucocorticoids (Table 3). In general, the choice of therapy is guided by the nature and severity of symptoms, comparative evaluation of the potential harms and benefits of each therapy, and patient preferences, with PPIs recommended as early or initial treatment by recent practice guidelines. There are limited data comparing these different therapies individually,Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and indirectness. Tomizawa Y, Melek J, Komaki Y, Kavitt RT, Sakuraba A. Efficacy of Pharmacologic Therapy for Eosinophilic Esophagitis: A Systematic Review and Network Meta-Analysis. J Clin Gastroenterol. 2018 Aug;52(7):596-606. doi: 10.1097/MCG.0000000000000878. PubMed PMID: 28787360. and there are no data on the use of 2 or more treatments in combination, either for those who have not responded to initial therapy or those who have concurrent GERD and EoE.

The goals of therapy are alleviation of symptoms and histologic remission (<15 eosinophils/HPF) in the short term, maintenance of remission and prevention of recurrent food bolus impaction in the medium and long term, and prevention of progressive fibrosis and strictures in the very long term.

Regardless of treatment, it is recommended that the effect of any therapeutic change should be evaluated by endoscopy and biopsy (usually after 6-12 weeks of treatment), because of the poor correlation between symptoms and histologic features. However, it should be recognized that this may be considered a significant burden by the patient and the payer.

Nutritional Management

Dietary therapy to prevent exposure to foods that trigger the immune response and inflammation is a common initial approach, particularly in children. Adults are usually less motivated to follow a precise, very restricted diet, which may have a substantial detrimental effect on the patient’s social life, nutritional status, financial commitments, and quality of life. Prolonged avoidance of food triggers may lead to sustained drug-free remission, but symptoms and inflammation commonly recur after diet discontinuation.

Elimination diets:

1) Hypoallergenic elimination diets involve the elimination of up to 6 most frequent sources of food allergens: milk, egg, fish/shellfish, nuts/peanuts, soy, and wheat (Table 3). An empiric six-food elimination diet (SFED) leads to histologic remission in about three-quarters of patients; stepwise food reintroduction may then identify the specific food triggers. Four-food (FFED) and two-food (TFED) elimination diets lead to histologic remission in about a half and one-third of EoE patients, respectively, but they are also less restrictive.

2) The targeted elimination diet is individually tailored to the patient on the basis of history, results of skin prick tests, and elimination and provocation tests. It leads to histologic remission in less than one-third of adult EoE patients.

3) The elemental diet is a particular type of commercial diet. Although it is well balanced and free of allergens, some patients cannot tolerate its taste. After 4 to 6 weeks of following the diet and achieving remission, individual foods are reintroduced one by one. The elemental diet is recommended only in case other elimination diets and pharmacotherapy have failed. In adults, the elemental diet should usually be supplemented with pharmacologic treatment.


1. PPIs: Currently there is limited information suggesting that PPIs (mostly esomeprazole) are comparable in efficacy to topical glucocorticoids.Evidence 2Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and indirectness. Tomizawa Y, Melek J, Komaki Y, Kavitt RT, Sakuraba A. Efficacy of Pharmacologic Therapy for Eosinophilic Esophagitis: A Systematic Review and Network Meta-Analysis. J Clin Gastroenterol. 2018 Aug;52(7):596-606. doi: 10.1097/MCG.0000000000000878. PubMed PMID: 28787360. However, there is a large body of observational evidence that PPIs relieve symptoms and reduce esophageal eosinophilia in EoE and this—along with the low cost, convenience, and good safety profile of PPIs—supports their use for initial treatment.

A standard-dose PPI, taken bid for 8 weeks, results in clinical remission in 60% of patients and histologic remission in 50% of patients. Maintenance treatment used for ≥1 year extends remission in 75% of patients who responded to treatment. In case of recurrence, in some patients the dose of the PPI may be increased.

2. Topical glucocorticoids: No agents are specifically designed for use in patients with EoE. Oral administration of inhaled glucocorticoid formulations is used: budesonide (2-4 mg/d, usually in divided doses; oral solution is prepared using nebulization suspension [0.5 mg/mL] mixed with sucralose 5 mg to increase viscosity) or fluticasone (1000-2000 microg bid via metered-dose inhaler; instruct the patient to activate the inhaler while holding their breath to deposit the drug in the mouth, and then to swallow the medication, which minimizes the amount of the drug delivered to the lungs). After administering these agents, the patient should not eat or drink for 30 to 60 minutes. Esophageal candidiasis is a possible adverse effect. Systemic glucocorticoids should not be used, as they are no more effective than topical therapy but are associated with more adverse events.

3. Nonglucocorticoid immunosuppressive drugs: There are case reports that azathioprine and 6-mercaptopurine may induce and maintain remission in a few patients but other medications, including disodium cromoglicate, antihistamines, montelukast, anti-interleukin (IL)-5 antibody, anti–IL-13 antibody, anti–tumor necrosis factor (TNF) antibody, and anti-IgE antibody, have all been ineffective.

Endoscopic Treatment

EoE patients who have an esophageal stricture that affects swallowing and do not respond to medical therapy should be offered endoscopic esophageal dilation. This is a generally safe procedure with a risk of perforation <1% and a mean duration of response typically >1 year.


EoE is a chronic disease that usually responds to therapy in the short term, but if treatment is stopped, most patients experience recurrent symptoms leading to reduced quality of life and possibly esophageal strictures. Long-term maintenance therapy seems appropriate for those with persistent symptoms, although there are very scarce data on long-term outcomes in EoE patients in the presence or absence of long-term therapy.


Table 7.2-1. Features differentiating EoE and GERD

Characteristic features



Coexisting atopic diseases


As in general population

Food hypersensitivity


As in general population


M > F

M = F

Dysphagia (particularly with allergenic foods)




Normal in most



Frequent lesions, characteristic appearance

Normal in 40%-60%



Distal esophagus

Proximal esophagus

Lesions present

Lesions present

Lesions present

Normal findings

Epithelial hyperplasia



Mucosal eosinophilia

>15 per HPF

0-7 per HPF



H2 blockers

Useful in some

Useful in some


Useful in some




No effect

Elimination diet


No effect

EoE, eosinophilic esophagitis; F, female; GERD, gastroesophageal reflux disease; HPF, high-power field; M, male; PPI, proton pump inhibitor.

Table 7.2-2. Conditions associated with esophageal eosinophilia (other than EoE or GERD)

Associated conditions


Eosinophilic gastritis, gastroenteritis, or colitis

With esophageal involvement

Crohn disease

With esophageal involvement

Esophageal motor disorders

– Achalasia of cardia

– Esophagogastric outlet obstruction

– Esophageal body dysmotility


Viral, fungal, bacterial


– Drug hypersensitivity reactions

– Pill esophagitis

Autoimmune disorders

– Connective tissue disorders

– Vasculitides

Dermatologic conditions

– With esophageal involvement

– Pemphigus vulgaris

Graft-versus-host disease


Mendelian disorders

– Marfan syndrome type II

– Hyper-IgE syndrome

– PTEN hamartoma tumor syndrome

– Netherton syndrome

– Severe atopy metabolic wasting syndrome


– Primary (neoplastic) HES

– Secondary (reactive) HES

– Idiopathic HES

Hypermobility syndromes

Ehlers-Danlos syndrome

EoE, eosinophilic esophagitis; GERD, gastroesophageal reflux disease; HES, hypereosinophilic syndrome; PTEN, phosphatase and tensin homolog.

Table 7.2-3. Medical treatment for eosinophilic esophagitis



Acid suppression


– Dexlansoprazole

– Esomeprazole

– Lansoprazole

– Omeprazole

– Pantoprazole

– Rabeprazole

Standard-dose PPI:

– Once daily or bid

– 8-12 weeks

Glucocorticoids (topical)

Fluticasone propionate:

– Metered-dose inhaler

– Spray (swallowed)

Infants: 44 microg inhaler 2 puffs bid

Children: 110 microg inhaler 2 puffs bid

Adults: 220 microg inhaler 2 puffs bid


– Nebulizer solution

– Swallowed as solution or in viscous sucralose slurry

Children: 0.25-0.5 mg bid

Adults: 1-2 mg bid

Dietary therapy

Elemental diet

– Amino acid–based formula (antigen-free)

– Oral intake: Poor adherence due to taste

6-food elimination diet

– Eliminate eggs, milk, nuts, seafood, soy, and wheat for 6 weeks

– If effective, reintroduce food groups individually every 6-8 weeks; repeat endoscopy and biopsy to evaluate response

4-food elimination diet

– Eliminate eggs, milk, soy, and wheat for 6 weeks

– If effective, reintroduce food groups individually every 6-8 weeks; repeat endoscopy and biopsy to evaluate response

2-food elimination diet

– Eliminate milk and wheat for 6 weeks

– If effective, reintroduce food groups individually every 6-8 weeks; repeat endoscopy and biopsy to evaluate response

bid, 2 times a day; PPI, proton pump inhibitor.

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