Eosinophilic Esophagitis: Brief Review

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist, Fort Lauderdale, Florida

Eosinophilic esophagitis (EoE) is an eosinophilic inflammation of the esophagus which was first reported in 1978.

IL-5 is the predominant mediators in the EoE inflammation. Both IL-5 and IL-13 cause release of eotaxin which attracts eosinophils.

The receptors for IL-3, IL-5, and GM-CSF share a common β chain. All 3 cytokines stimulate the development of eosinophils.

Eosinophilic Esophagitis (click here to enlarge the image).

Clinical Manifestations

EoE is a common cause of dysphagia in children. Adult patients are usually men (3:1 M:F) in their 30s or 40s.

Presenting symptoms:
- dysphagia 93%
- food impaction 62%
- heartburn 24%

50-80% of the patients have a history of allergies. A family history of atopic disease is present in 74%.

Peripheral blood eosinophilia

31% have peripheral blood eosinophilia. Blood eosinophilia is not diagnostic and the correlation with disease activity is not established.

Total Immunoglobulin E (IgE)

Serum IgE levels are increased in 55% of patients but total IgE cannot serve as a marker for disease progression or resolution.

Natural History

EoE is a chronic disease with persistent or relapsing symptoms. Esophageal metaplasia (Barrett's esophagus or cardia-type metaplasia) has not been described in EE (different from GERD).


How to diagnose EoE?

EoE is diagnosed by a biopsy of the esophagus which shows more than 15 eosinophils per HPF. Biopsy specimens should be obtained regardless of the gross appearance of the mucosa.

A peak count of at least 15 intraepithelial eosinophils per HPF is an absolute minimum number to make the diagnosis of EoE. At least 1 HPF must contain at least 15 intraepithelial eosinophils.

Patients with GERD-related esophagitis have fewer than 10 eosinophils per HPF. Any eosinophil number larger than 0 in esophagus is abnormal.

Eosinophils ascend in number as one descends in the GI tract:

0 eosinophils in esophagus
2 eosinophils in stomach
5 eosinophils in small bowel
15-50 eosinophils in large bowel

This eosonophils distribution may have evolved in the evolution to protect the body against parasitic infections ("sitting there waiting for parasites").

Endoscopic findings (abnormal in 91% of patients):

- mucosal fragility 59%
- rings or corrugated lining 49%
- strictures 40%

A corrugated esophagus characterized by fine concentric mucosal rings is a hallmark of EE. One hypothesis explains this by acetylcholine release which contracts muscle fibers in the muscularis mucosae resulting in the formation of concentric esophageal rings.

The rings or corrugated lining make the esophagus look like trachea during EGD. Some authors have called eosinophilic esophagitis "asthma of the esophagus." The changes in esophageal mucosa are reminiscent of airway remodelling in asthma.

Allergic Evaluation

Patients with EoE have a higher incidence (50-80%) of allergic rhinitis, asthma, and atopic dermatitis. Some authors have called eosinophilic esophagitis "asthma of the esophagus." An evaluation by an allergist for other atopic diseases is recommended. Skin prick testing for foods and environmental allergens (aeroallergen) should be considered in all patients.

- Food allergy: multiple food sensitizations are found in 80% of patients
- Aeroallergens: multiple environmental sensitizations are found in 90% of patients

The presence of allergic rhinitis, sensitization to aeroallergens, or both ranges from 42% to 93% in children with eosinophilic esophagitis. In addition, dietary therapy has a role in EoE treatment. According to the most recent consensus document, children with eosinophilic esophagitis should be evaluated for food and aeroallergen sensitization (Liacouras CC, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011 (July); 128(1):3-20).

Peripheral Cytokines

Eotaxin-3 expression is a promising marker for distinguishing EoE from other causes of esophagitis. Both IL-5 and IL-13 cause release of eotaxin which attracts eosinophils.


Currently, there is no FDA-approved treatment for eosinophilic esophagitis. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation (Allergy, 2012).

Some treatment to eosinophilic esophagitis can be summarized by the following mnemonic: SADD

Steroids (local, PO)
Acid suppression with PPI
Diet (6- or 8-food elimination diet)
Dilatation of esophagus (if strictures)

Some experts advise to choose one course of therapy: medical OR diet.


Both systemic and topical corticosteroids are effective for therapy of EoE but pathological findings and symptoms reccur when discontinued.

When to use systemic corticosteroids in EoE?

In emergent cases such as dysphagia requiring hospitalization, dehydration because of swallowing difficulties, and weight loss.

Topical corticosteroids

Topical corticosteroids are often helpful when used in the setting of EoE, 87% of children respond to topical budesonide.

Two inhaled corticosteroids have been used to treat eosinophilic esophagitis - fluticasone and budesonide.

The usual starting dose of budesonide in an adult is a 1 mg ampule mixed with a slurry of artificial sweetener (usually sucralose) using 10 packets, dependent upon taste, and swallowed b.i.d. In a child, 0.5 mg can be used in the same way, mixed with 5 packets.

Fluticasone is typically started at a dose of 440 mcg b.i.d. This can be lowered to 220 mcg b.i.d. subsequently.

Starting dose is 440-880 micrograms per day for children and 880-1760 micrograms per day for adolescents/adults. This regimen is continued for at least 6-8 weeks, depending on the response. Several studies have shown that the eosiniphilic infiltration returns when the swallowed steroids are stopped.

Leukotriene receptor antagonists (Singulair) and cromolyn are not useful for treatment of EE.

How to use steroids for topical treatment of EoE?

Patients should be instructed to use a metered dose inhaler (MDI) without a spacer. MDI is inserted in the mouth and sprayed with lips sealed around the device. The powder is swallowed and not rinsed (just the opposite of using MDI in asthma). Patients should not eat or drink for at least 30 minutes.

Acid Suppression

In patients with EoE, symptoms are unresponsive or only partially responsive to acid blockade with PPIs. PPI therapy is not a primary treatment for EE but rather a co-therapy. Children with eosinophilic esophagitis (EoE) treated with PPIs show an improvement in symptoms despite persistent eosinophilic inflammation. PPI treatment may be useful maintenance therapy in children with EoE (Annals of Allergy&Immunology, 2012).

Dietary Treatment

- Elimination diet (6-food elimination diet: peanut, milk, egg, soy, seafood, wheat)
- Elemental diet

Dietary therapy (specific antigens removal or elemental formula) can be useful in children with EoE. Skin prick testing for foods and environmental allergens (aeroallergen) should be considered in all patients.

Elemental diet "cures" 95% of EoE but is difficult to implement.

Esophageal Dilatation

Esophageal dilatation is useful for patients with fixed esophageal strictures causing food impaction. Medical therapy should be attempted first.

Monitoring of therapy in EoE

One approach is to perform repeated EGDs with biopsy every 4-6 months until esophageal eosinophilia is resolved.

What is the most potent chemokine (chemoattractant) for eosinophils?

(A) IL-5
(B) IL-8
(C) LTB4
(D) eotaxin
(E) IL-4
(F) IL-13

Answer: D.

Eotaxin is the most potent chemoattractant for eosinophils but IL-5 is the most specific stimulant of their production.


Eosinophilic Esophagitis. NEJM Images.
Potential pathogenesis and effects of tissue remodeling in patients with EoE. JACI Images, Nov 2011.
Eosinophilic esophagitis: the newest esophageal inflammatory disease. Atkins, D. et al. Nat. Rev. Gastroenterol. Hepatol. 6, 267–278 (2009) (PDF).
Eosinophilic Esophagitis. Harrison's Online.
Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. National Guideline Clearinghouse.
Eosinophilic disorders. JACI, Volume 119, Issue 6, Pages 1291-1300 (June 2007).
Eosinophilic oesophagitis. Alyson Kakakios and Ralf G Heine. MJA 2006; 185 (7): 401.
Eosinophilic Oesophagitis: A Common Cause of Dysphagia in Young Adults? Medscape, 11/2008.
Eosinophilic esophagitis after specific oral tolerance induction for egg protein http://goo.gl/fzmip


Eosinophilic Esophagitis. The DAVE Project - Gastroenterology.

Related reading

Proton-Pump Inhibitors (PPIs) Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel Use http://goo.gl/zANv
Repeating allergy testing in children with eosinophilic esophagitis whose original tests were negative. Ask the Expert, AAAAI, 2011.
Reslizumab (anti-IL5) led to improvements in histology, but not in symptoms in eosinophilic esophagitis. Medscape, 2012.
Eosinophilic Esophagitis treatment strategy relies on 3 D's: drugs, diets, dilation (free full text review), 2012.

Comments from Twitter

@DrSilge: Dr. Aceves says that they use 0.5 mg budesonide respules in 5 packets, not the 1 mg. If need higher dose, use 10 packets. She states that want the volume for surface area, moreso than the higher concentration of medication.

Dr John Weiner @AllergyNet: Not just hot topic, but burning, summarized superbly by @Allergy

Published: 08/09/2008
Updated: 05/21/2012

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