Eosinophilic Esophagitis in Children

Educational Objectives

The goal of this program is to improve the diagnosis and management of eosinophilic esophagitis (EoE). After hearing and assimilating this program, the clinicians will be able to:

1. Diagnose EoE in patients presenting with clinical symptoms of esophageal dysfunction.
2. Use appropriate testing and imaging modalities in patients with suspected EoE.
3. Select an appropriate treatment option for EoE based on drug efficacy, associated risks, and indications in various age groups.

Summary

Eosinophilic esophagitis (EoE): a chronic immune-mediated esophageal disease; diagnosis requires clinical symptoms of esophageal dysfunction and pathologic findings (eosinophil-rich inflammation, defined as ≥15 eosinophils per high-powered field [HPF] in ≥1 biopsy); pathophysiology — normally, the esophagus should have no eosinophils per HPF; any count >0 indicates an issue; eosinophils are typically found farther down the gastrointestinal (GI) tract; EoE involves exposure to dietary or airborne allergens, causing eosinophils to accumulate at the surface of the tissue; eosinophils release inflammatory mediators, leading to esophageal dysfunction; age of onset — bimodal, with peaks in school-age children and adults in their late 20s to early 30s

Symptoms of EoE: include feeding difficulties, eg, poor eating habits and occasional vomiting; pain and swallowing issues are rare; in teenagers, swallowing difficulties or food sensation occurs; in adults (20s-30s), food impaction episodes (linked to the chronic nature of the disease) increase; EoE leads to chronic inflammation (esophagitis) and scarring (esophageal wall remodeling), causing fibrosis and strictures over time; ≤80% of food impactions in the emergency department result from underlying EoE

Presentation in pediatric patients: patients may have persistent reflux symptoms (become relevant when discussing gastroesophageal reflux disease [GERD]); if GERD-like symptoms persist in children, EoE should be considered; symptoms include vomiting, difficulty swallowing, and occasional food impaction; subtle signs might include slow eating, food cutting, water consumption with bites, and mealtime gagging; some might even refuse food or feel food movement from mouth to stomach; more common in boys but also occurs in girls; patients are often thin; atopy may manifest as asthma or known food allergies, often with a familial link; peripheral eosinophilia may be a clue but is not diagnostic; a cluster of atopic symptoms, seasonal allergies, wheezing, and family history are indicators; symptoms, including heartburn, overlap with GERD

Endoscopic features of EoE: direct esophageal examination is the definitive diagnostic approach for EoE confirmation; distinctive endoscopic features include rings, linear tracks, furrows, edema, white plaques (eosinophilic clusters), and exudates, which can appear alone or together; in contrast, a healthy esophagus appears pink, robust, and vascular

Histologic features: include degranulation and microabscesses; esophageal swelling is visible, with basal layer hyperplasia and dilated intracellular spaces; EoE affects the entire esophageal wall, signifying a transmural process

Initial evaluation: upper GI imaging is a reasonable initial diagnostic step especially for detecting strictures before endoscopy; guidelines suggest considering proton pump inhibitor (PPI) treatment for GERD symptoms, especially in teens with classic heartburn; consultation with a gastroenterologist is advised; some patients respond remarkably to PPIs, with complete elimination of eosinophils

Upper GI findings: classic findings include a small-caliber esophagus because of inflammation-induced constriction; ring-like structures may also be visible on imaging; the main goal is to exclude strictures or other causes

Diagnosis: establish the diagnosis before EoE treatment is initiated; biopsy is vital, as visual assessment alone is inadequate

Treatment Options for EoE

Pharmacologic therapy: PPIs benefit certain patients; topical steroids are notably effective, whereas systemic options, (eg, oral prednisone, methylprednisolone [eg, Depo-Medrol, Medrol, Solu-Medrol]) are rarely used because of the chronic nature of the disease; long-term use of systemic steroids is generally avoided; topical steroids can be a lasting therapy; biologics are now available; dupilumab was approved by the US Food and Drug Administration (FDA) in May 2022 for EoE in ages ≥12 yr; pediatric approval is sought for younger ages; dupilumab is also approved for eczema in children ≥6 mo of age

Dietary exclusions: complete removal of dietary proteins via an elemental diet (using amino acid [AA]-based formulas) can decrease eosinophils; however, relying solely on these formulas for lifelong management is not practical; some diets eliminate specific triggers; for older patients, dilation might be necessary for strictures, but this is less common in children

Steroids: topical steroids, primarily used for asthma, pose delivery challenges; innovative methods, eg, budesonide slurry, adhere to esophageal walls; instructing the patient to swallow the mist from an inhaler is another option; topical steroids decrease eosinophil counts, but the eosinophils return when the steroid is discontinued; topical steroids are also associated with esophageal candidiasis and adrenal suppression; systemic steroids are effective but limited to rare cases

Evolution of dietary restrictions: in 1995, Kelly et al found that patients with EoE benefited from AA-based formulas (reduced symptoms and eosinophils); studies from the Children’s Hospital of Philadelphia confirmed these benefits; discussions in the early 2000s highlighted the impracticality of long-term AA diets, leading to allergy-based directed elimination tests; empiric elimination diets are now favored; shifting from complete elimination, a newer approach targets a single food trigger; 8 common allergenic foods (now 9 with sesame) make up ≈90% of US food allergies; milk is the most common; US FDA regulations, labeling, and advanced tests (eg, skin prick, patch tests) enhance accurate allergic response assessment

Immunoglobulin E (IgE) mediation: EoE is primarily a non-IgE-mediated gut reaction; Th1 and Th2 reactions trigger EoE, with Th2 being more common

Empiric elimination diets: easier to initiate and seem to be more effective than directed elimination diets; the 6-food elimination diet targets key triggers, ie, milk, soy, egg, wheat, beef, fish; removing these for 6 wk reduces eosinophils; however, reintroduction challenges lead to eosinophil recurrence; most patients with EoE average 4 to 5 foods; elemental food diets are effective but intolerable for most patients; the 6-food elimination diet achieves 70% to 74% success, and 4-food elimination diet achieves ≈50%; Kagalwalla et al (2012) found that solely removing milk achieves a 65% response rate; the speaker primarily focuses on eliminating dairy products from the diet; the patient must still consume sufficient amounts of protein, calcium, and vitamin D; consult with a dietician; various dietary tools are available; elemental formulas benefit toddlers with EoE; older children may show subtle EoE symptoms despite being otherwise healthy

Readings

Benitez AJ, Hoffmann C, Muir AB, et al. Inflammation-associated microbiota in pediatric eosinophilic; Chehade M, Aceves SS. Food allergy and eosinophilic esophagitis. Curr Opin Allergy Clin Immunol. 2010;10:231-237; Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis: proceedings of the AGREE conference. Gastroenterol. 2018;155:1022-1033; Fujiwara Y. Symptom-based diagnostic approach for eosinophilic esophagitis. J Gastroenterol. 2020;55:833-845; Kagalwalla AF, Amsden K, Shah A, et al. Cow's milk elimination: a novel dietary approach to treat eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2012;55(6):711-716. doi:10.1097/MPG.0b013e318268da40; Kelly KJ, Lazenby AJ, Rowe PC, et al. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology. 1995;109(5):1503-1512. doi:10.1016/0016-5085(95)90637-1; Kim HP, Vance RB, Shaheen NJ, et al. The prevalence and diagnostic utility of endoscopic features of eosinophilic esophagitis: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10:988-996; Liu X, Xiao X, Liu D, et al. A meta-analysis on randomized controlled trials of treating eosinophilic esophagitis with budesonide. Ann Med. 2022;54:2078-2088; Murali AR, Gupta A, Attar BM, et al. Topical steroids in eosinophilic esophagitis: Systematic review and meta-analysis of placebo-controlled randomized clinical trials. J Gastroenterol Hepatol. 2016;31(6):1111-1119; Nhu QM, Aceves SS. Current state of biologics in treating eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2023;130:15-20.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Lightdale was recorded at the 55th Annual Advances and Controversies in Clinical Pediatrics, held May 31 to June 3, 2023, and presented by the University of California, San Francisco, School of Medicine. For more information about the upcoming CME activities from this presenter, please visit https://meded.ucsf.edu/ continuing-education. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

PD694001

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.