Therapeutic Modalities

The 3 main treatments for EoE are medication, dietary therapy, or mechanical dilation of the esophagus. Patients should be evaluated individually to address their most problematic complaints first, and therapy should be tailored based on patient preference. Debate exists among the medical community whether therapeutic goals should be defined by clinical or histologic remission with various reported thresholds of permissible esophageal eosinophilia.

Pharmacotherapy

Treatment with PPIs can be effective in up to 50% of patients when used as primary therapy for EoE, particularly in those with PPI-REE.4,6 Although some researchers believe this diagnosis is defined by the presence of both GERD and EoE, more investigation is necessary to find its etiology.


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Swallowed topical steroids are often considered as first-line therapy for EoE. Both swallowed fluticasone propionate (aerosolized) and budesonide (mixed with a thickener and sweetening agents) have been shown to be effective and well tolerated.7,8 These medications target the inflammatory response locally as they travel down the esophagus after ingestion. In a double-blind, placebo-controlled trial, fluticasone propionate was found to be 90% effective in pediatric patients.7  In another randomized, double-blind, placebo-controlled trial, oral budesonide for 15 days significantly decreased the number of eosinophils in the esophageal epithelium (from 68.2 eosinophils/hpf to 5.5 eosinophils/hpf) compared with placebo (from 62.3 eosinophils/hpf to 56.5 eosinophils/hpf).8  Although generally safe and tolerated, potential side effects from these medications can include development of Candida esophagitis, growth delay, adrenal insufficiency, reduced bone density, and cataracts, particularly with fluticasone.7  Oral systemic steroids ( eg, prednisone) are effective for EoE but are used sparingly due to their systemic side effect profile. In general, topical steroid therapy is effective for treating EoE, but medication duration is indefinite, as the root of the disease (ie, food allergy) has not been addressed.

Dietary Interventions

Dietary treatments for EoE include targeted elimination therapy, elimination therapies, and elemental dietary therapy. Targeted elimination therapy, also known as skin test-directed elimination, aims to exclude from a patient’s diet only the foods for which allergy testing is positive. Empiric elimination therapies can be further categorized into a milk elimination diet, 2-food group elimination diet, 4-food group elimination diet, and 6-food group elimination diet. Milk elimination, in which patients avoid milk protein without having previously tested positive for a milk protein allergy, is one of the newest empiric approaches to treating EoE.9 In a retrospective study assessing the effect of a cow’s milk elimination diet on children with EoE, Kagalwalla et al reported a clinical and histologic remission in 65% of the sample population.10

The 2-food, 4-food, and 6-food group elimination diets consist of initially removing the respective number of food proteins from the diet including those derived from milk, eggs, soy, wheat, peanuts/tree nuts, and/or seafood, which are the proteins most commonly associated with the development of food allergies and most commonly reported to cause esophageal injury in patients with EoE.9 In a step-up dietary treatment approach, patients who do not have a clinicohistologic response to a 2-food group elimination diet (eg, milk and gluten) are then offered to step up to a 4-group and subsequent 6-group elimination diet if necessary.9 Once patients achieve remission on any of the empiric diet therapies, they reintroduce an eliminated food group and then undergo re-evaluation via endoscopy and biopsy. Depending on the eosinophil count of the esophageal biopsy, a food group is deemed either tolerated and then retained in the diet or labeled as a trigger and removed from the patient’s diet indefinitely. Finally, the elemental dietary therapy uses formulas containing exclusively proteins that have been hydrolyzed into their simplest form, amino acids. These formulas are often associated with diet nonadherence in both children and adults who have previously tolerated a regular diet as they are often unpalatable and expensive. The use of the elemental dietary therapy in young children may provide the dual benefit of remission from EoE as well as complete nutrition for a short period; however, long-term use in this population may eventually impede oromotor function.11

With each of these diets, the goal is to methodically and sequentially advance a patient’s diet until achieving the one that is the least restrictive while maintaining clinical and histologic remission of EoE. When comparing each of these dietary therapies for pediatric EoE, Henderson et alfound the following: the elemental diet was the most effective with a 96% remission rate, the empiric 6-food elimination diet had an 81% remission rate, and the skin test-directed diet had a 65% remission rate.12 In the adult population, Peterson et al found a 75% histologic remission rate with an elemental diet but no symptom improvement and high drop-out rates.13 A 94% clinical response and a 70% histologic response were noted in an adult population with EoE tried on the 6-food elimination diet in a prospective study by Gonsalves et al.14 Adults with EoE were shown to have 68% improvement in symptoms and a 32% histologic response in a retrospective cohort study performed by Wolf et al.15 Dietary therapy ultimately identifies the root cause of EoE disease and often is preferred by patients reluctant to use medications indefinitely.

Mechanical Dilation

Esophageal dilation, a procedure during which a balloon is used to expand the diameter of the esophagus to allow for immediate symptomatic relief, is the least desirable means of treating EoE. However, it is the only treatment for narrow esophageal strictures. Due to the risk of chest pain, deep mucosal tears, esophageal perforation, and increased postendoscopic pain, dilation is not preferred as initial therapy. The goal of treating EoE early with medication or dietary therapy is to prevent fibrosis and strictures from occurring, thereby reducing the need for dilation therapy.

Regardless of the treatment implemented, one of the most challenging aspects of EoE from a patient’s perspective is the need for frequent endoscopies to monitor therapeutic efficacy, as this is time-consuming, costly, and associated with procedural risks. As such, judicious use of these procedures is recommended. Finding a noninvasive screening method to monitor treatment efficacy would be highly advantageous for patients.

Prognosis

EoE is a chronic relapsing and remitting disease without cure requiring long-term, routine therapy to prevent recurrence. Straumann et al followed 30 adult patients with EoE for 7 years and found that only 10% of patients experienced resolution of the disease.1 To make an important distinction from chronic GERD, EoE has not been associated with risk for esophageal cancer, nor is there evidence linking EoE to increased mortality. However, cases have been reported in which patients with EoE were also diagnosed with Barrett esophagus, a disease that predisposes patients to esophageal cancer.2

The risk of further stricture formation and narrowing of the esophagus causing subsequent food impaction should be considered when weaning or discontinuing a patient’s medication as the recurrence of esophageal symptoms is expected if treatment is discontinued. In fact, studies have reported a clinical and histologic recurrence of up to 90% among adult patients with EoE within 13 months of discontinuing topical steroid therapy.1 Although the entity of EoE is still in its early stages of clinical and scientific exploration, researchers aim to find more curative treatment options in the future.

Conclusion

The presentation of EoE can be similar to other gastrointestinal disorders, but the therapies that provide symptomatic and histologic remission are dissimilar. Therefore, it is important for medical practitioners to consider EoE in the differential diagnosis when evaluating dysphagia. Although the diagnostic criteria for EoE are straightforward, the various maintenance therapies and the need for frequent endoscopies can make disease management challenging for both patients and providers.

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Alison Miller, MPAS, PA-C, is a physician assistant at GI Care for Kids, and Seth Marcus, MD, MSCI, is a pediatric gastroenterologist at GI Care for Kids, in Atlanta, Georgia; Alicia Elam, PharmD, is an associate professor in the physician assistant department of Augusta University, in Augusta, Georgia.

References

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2. Richter JE, Castell JE. The Esophagus. 5th ed. Hoboken, NJ: John Wiley & Sons; 2011.  

3. Greenberger NJ, Blumberg RS, Burakoff R. Eosinophilic esophagitis. In: Current Diagnosis & Treatment Gastroenterology, Hepatology, & Endoscopy. 2nd ed. New York: McGraw Hill Medical; 2012:183-186.

4. Lucendo AJ, Molina-Infante J, Arias Á, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J. 2017;5(3):335-358.

5. Odiase E, Schwartz A, Souza RF, Martin J, Konda V, Spechler SJ.  New eosinophilic esophagitis concepts call for change in proton pump inhibitor management before diagnostic endoscopy. Gastroenterology. 2018;154(5):1217-1221.

6. Molina-Infante J, Katzka DA, Gisbert JP. Review article: proton pump inhibitor therapy for suspected eosinophilic oesophagitis. Aliment Pharmacol Ther. 2013;37(12):1157-1164.

7. Konikoff MR, Noel RJ, Blanchard C, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006;131(5):1381-1391.

8. Straumann A, Conus S, Degen L, et al. Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology. 2010;139(5):1526-1537.

9. Arias Á, González-Cervera J, Tenias JM, Lucendo AJ. Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis. Gastroenterology. 2014;146(7):1639-1648.

10. Kagalwalla AF, Amsden K, Shah A, et al. Cowʼs milk elimination: a novel dietary approach to treat eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2012;55(6):711-716.

11. Wechsler J, Schwartz S, Amsden K, Kagalwalla A. Elimination diets in the management of eosinophilic esophagitis. J Asthma Allergy. 2014;7:85-94.

12. Henderson CJ, Abonia JP, King EC, et al. Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2012;129(6):1570-1578.

13. Peterson KA, Byrne KR, Vinson LA, et al. Elemental diet induces histologic response in adult eosinophilic esophagitis. Am J Gastroenterol. 2013;108(5):759–766.

14. Gonsalves N, Yang G-Y, Doerfler B, Ritz S, Ditto AM, Hirano I. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 2012;142(7):1451–1459.e1.

15. Wolf WA, Jerath MR, McConville S, Shaheen NJ, Dellon ES. Su1842 dietary elimination therapy is an effective option for adults with eosinophilic esophagitis. Gastroenterology. 2013;144(5):S-488.