Eosinophilic Esophagitis: The New Kid on the Block

The Great GERD Imposter: How EoE Has Gained Fame

Gastrointestinal (GI) disorders are amongst the most prevalent conditions in the United States, resulting in millions of healthcare encounters on an annual basis.¹  Symptoms such as nausea, heartburn, indigestion, and dysphagia rank amongst the top ten symptoms prompting ambulatory care visits on an annual basis.¹ As a result, both gastroesophageal reflux disease (GERD) and reflux esophagitis are the third leading GI diagnoses in the United States.¹  Patients with symptoms of GERD, regurgitation, or dyspepsia often seek help first from their pharmacist, resulting in millions of recommendations each month for nonprescription acid suppressants and antacids.² While upper GI symptoms related to conditions such as GERD are highly prevalent, further investigation of symptomatic patients of over the last 20-30 years has resulted in the emergence of a previously unrecognized disorder referred to as eosinophilic esophagitis (EoE). While much is yet to be learned about EoE, its contribution to the development of upper GI symptoms and complications has resulted in an explosion of research into its causes and potential treatments. Given the increasing awareness of EoE, there is a need for us to get to know this new kid on the block. Below I will briefly summarize the current understanding of the disease process and the recommended treatments.

The Angry Eosinophil: Why the Esophagus is Targeted in EoE

Once thought to be a subtype of GERD, EoE is now recognized as chronic inflammatory disease of the esophagus characterized by eosinophilic infiltration into the esophageal mucosa.^3,4  The prevalence of EoE in Western countries is approximately 1 in 2500 individuals, and it occurs in both children and adults.³ The disease process is thought to be a Th2-mediated inflammatory response largely triggered by esophageal exposure to food or aeroallergens.^3-5  This may include all or some of the major food groups, such as dairy, wheat, soy, eggs, peanuts and tree nuts, and shellfish.⁵ The resulting eosinophilic infiltration initiates further recruitment of other immune cells, such as mast cells, basophils, Langerhans cells, B-cells, and myofibroblasts.⁵ These cells then initiate and propagate the release of various inflammatory mediators, such as interleukins, eotaxins, thymic stromal lymphoietin (TSLP), and transforming growth factor β (TGF- β), amongst others. ^3-5 Various receptors for these mediators are involved in the disease process, such as IL-4R, IL-5R, IL-13R, sialic binding Ig-like lectin-8 (Siglec-8), CRTH2, and integrin receptors.^3-5 The resulting ongoing inflammatory cascade leads to damage and fibrosis of the esophagus, resulting in dysmotility, stricture, and enhanced permability.⁵ The presence of other atopic diseases, such as asthma, allergic rhinitis, atopic dermatitis, and food allergies are found in up to 60% of patients with EoE.^3-5

The Clinical Conundrum: Identifying when it may be EoE

The clinical presentation of EoE is variable and may differ based on the patient’s age. In young children and infants, symptoms are often non-specific and may include failure to thrive, difficulty with feedings, heartburn, or vomiting. ⁴ Children may adopt a variety of coping behaviors related to eating, such as slow eating (resulting in extended duration of meals), extensive chewing of food, preferentially consuming liquids or soft foods, avoiding certain food textures such as meat, rice, and bread, and avoiding social dining due to fear of food getting stuck.^5.6 In adolescents and adults, food impaction and dysphagia are the most common presenting symptoms, and are typically indicative of established fibrosis and esophageal stricture or dysmotiliy.^5,6 The diagnosis of EoE cannot be made solely on the presence of symptoms, and requires the addition of endoscopy with biopsy of the esophageal mucosa and visualization of common complications. The presence of greater than 15 eosinophils per high powered field upon biopsy is considered diagnostic for EoE.^6,7

Treatment Approaches for EoE: It’s not All About the Acid

The approach to treatment of EoE involves endoscopic dilation, elimination diets, and pharmacologic interventions. In 2020 guidelines for the management of EoE were published to provide insight on the positioning and effectiveness of these interventions.⁷ Given the nature of the disease process, interdisciplinary collaboration amongst gastroenterologists, pharmacists, primary care providers, and dieticians is often required. Endoscopic dilation is most effective for patients with dysphagia and stricture.⁷ While effective in alleviating symptoms, dilation does not address the underlying inflammatory process, and thus is considered an adjunctive approach.

Food Fight! The Role of Dietary Interventions in the Treatment of EoE

Dietary intervention in EoE is largely focused on eliminating food triggers from the diet. This is accomplished by starting with either a strict elemental diet, or eliminating 2, 4, or 6 of the common food allergens (dairy, wheat, soy, eggs, peanuts and tree nuts, and shellfish) from the diet, and then re-introducing the foods one at a time to see if symptoms are triggered.^6-8 Each time a food group is re-introduced the patient must undergo endoscopy with biopsy to gauge if there is a reduction in esophageal eosinophil counts.  Adhering to elimination diets can be challenging for patients, particularly if elemental or 6-food elimination diets are used. Patients may also be placed at risk for nutrient deficiencies with higher number of foods that are eliminated. Here is a summary of the most common dietary approaches.

1FED Diet 

– Foods eliminated: DAIRY

– Potential deficiencies: PROTEIN, CALCIUM, VITAMIN D

4FED Diet 

– Foods eliminated: DAIRY, WHEAT, EGG, SOY

– Potential deficiencies: PROTEIN, IRON, FIBER, B VITAMINS

6FED Diet 

– Foods eliminated: DAIRY, WHEAT, EGG, SOY, PEANUT/TREE NUT, FISH/SHELLFISH

– Potential deficiencies: ESSENTIAL FATTY ACIDS

Elemental Diet 

– Foods eliminated: AMINO ACIDS

– Potential deficiencies: MICRONUTRIENTS

[FED = Food Elimination Diet]

Drug Treatment of EoE:  Trying to Hit the Right Target

Pharmacologic interventions in EoE are often used in conjunction with dilation and dietary interventions. While investigation into various therapies is ongoing, there are currently no FDA approved treatments for EoE. The most common drug classes used in the treatment of EoE are proton pump inhibitors (PPIs) and swallowed topical corticosteroids (STCs). PPIs are thought to possibly reduce chemokine expression in epithelial cells. While often used, the effectiveness of PPIs is lacking, with only approximately 40% of patients achieving a histologic response.⁴ Despite this, PPIs are considered a reasonable option to start given their relative overall favorable safety profile.⁷ Recommended doses are 20-40 mg twice daily of omeprazole equivalent.

Budesonide and fluticasone are the two most STCs used for EoE. Given there are no approved formulations of these products, patients are instructed to mix the budesonide solution with sucralose or use the fluticasone metered dose inhaler and swallow the contents of each spray. Typical doses for budesonide are 1 mg twice daily and 440-880ug twice daily for fluticasone.^4-7 The STCs are effective in approximately 65% of patients, however questions remain about sustainability of their long term use and challenges with patient use and adherence as well as third party reimbursement given the off-label use.

There are currently many other agents being studied focused on targeting some of the more specific inflammatory pathways involved in the pathophysiology of EoE, such as ILs and Siglec-8. While we anxiously await the results of these trials, we should have an enhanced awareness of the current approaches to managing this emerging disease state.

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