Advances in Clinical Management of Eosinophilic Esophagitis

doi:10.1053/j.gastro.2014.07.055

Gastroenterology

Volume 147, Issue 6, December 2014, Pages 1238-1254

https://doi.org/10.1053/j.gastro.2014.07.055 Get rights and content

Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsy specimens, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor–responsive esophageal eosinophilia. We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histological features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and proton pump inhibitor–responsive esophageal eosinophilia. It is also important to consider the epidemiology of EoE (with a current incidence of 1 new case per 10,000 per year and prevalence of 0.5 to 1 case per 1000 per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids, such as fluticasone and budesonide, or dietary strategies, such as amino acid–based formulas, allergy test–directed elimination diets, and nondirected empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenotic complications of EoE. There are a number of unresolved issues in EoE, including phenotypes, optimal treatment end points, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines; EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians.

Section snippets

Definition

EoE is a chronic, immune-mediated clinicopathologic disease.1, 2, 3 The following criteria are required for diagnosis: symptoms of esophageal dysfunction; eosinophilic inflammation localized to the esophagus, with at least 15 eosinophils/high-power field (hpf) in esophageal mucosal biopsy specimens; and exclusion of other recognized causes of esophageal eosinophilia, including proton pump inhibitor–responsive esophageal eosinophilia (PPI-REE).2, 3 To fulfill the last criterion, patients must be

Features in Children

Children typically present with one or more symptoms such as vomiting, regurgitation, nausea, epigastric or abdominal pain, chest pain, water brash, globus, or decreased appetite.⁹ Less common symptoms include growth failure and hematemesis. Infants and toddlers are more likely to present with difficulty feeding, manifest as gagging, choking, refusal of food, and vomiting. Dysphagia is not commonly seen until adolescence.10, 11 The evaluation of young children is necessarily affected by

Challenges

Although the criteria for diagnosis of EoE seem straightforward, there are a number of challenges in diagnosing this disorder. Esophageal eosinophilia is not specific to EoE, so other disorders on the differential diagnosis must be considered (Table 1).1, 2, 3 Eosinophilic gastroenteritis with esophageal involvement should be assessed by analysis of gastric and duodenal biopsy specimens. Hypereosinophilic syndrome is a concern when the peripheral blood eosinophil count is >1500 × 10⁹ cells/L.

Epidemiology

EoE is a global disease, with large numbers of cases reported in North and South America, Western and Eastern Europe, and Australia. Fewer cases have been reported in Asia and the Middle East, and no cases have yet been reported in India or Sub-Saharan Africa.⁸⁶ EoE affects patients of any age, although it is more common in children and adults younger than 50 years of age.2, 8, 12, 87, 88 Men are affected more commonly than women, consistently in a ratio of 3 to 4:1; most patients with EoE have

Treatment

Treatment of EoE is based on its pathogenesis.¹¹⁶ In brief, EoE is believed to be a T-helper 2 cell–mediated immune response (involving interleukin [IL]-4, IL-5, and IL-13) to food and/or environmental allergens. IL-5 supports eosinophil differentiation and maturation, and IL-5 and IL-13 stimulate the esophageal epithelium to produce eotaxin 3, a potent chemokine that recruits eosinophils into the esophagus. Activated eosinophils release multiple factors that promote local inflammation and

Emerging Concepts and Unresolved Issues

EoE is a dynamic field, and the pace of knowledge acquisition has been astounding for a recently recognized disease. The fact that 3 practice guidelines have been published within the past 6 years illustrates this point. As such, it is understandable that many questions remain.

Conclusions

EoE is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. A management algorithm is presented in Figure 6. Diagnosis is based on symptoms of esophageal dysfunction, demonstration of ≥15 eosinophils/hpf in esophageal biopsy specimens, and exclusion of competing causes of esophageal eosinophilia, including PPI-REE. Esophageal eosinophilia in and of itself

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Cited by (176)

Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis
2024, Clinical Gastroenterology and Hepatology
Dupilumab is approved for treatment of eosinophilic esophagitis (EoE), but real-world data are lacking. We aimed to determine the real-world efficacy of dupilumab in patients with severe, treatment-refractory, and fibrostenotic EoE.
We conducted a retrospective cohort study of EoE patients prescribed dupilumab and who were treatment-refractory to standard modalities. Patient demographics, clinical characteristics, EoE history, and procedural data (including the histologically worst, predupilumab, and postdupilumab endoscopies) were extracted from medical records. Symptomatic, endoscopic, and histologic responses were assessed for the worst and predupilumab endoscopies compared with the postdupilumab endoscopy.
We identified 46 patients with refractory fibrostenotic EoE who were treated with dupilumab. Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the predupilumab esophagogastroduodenoscopies. The peak eosinophil counts decreased markedly, and postdupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field and 6 or fewer eosinophils per high-power field, respectively, and the Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all). Although the proportion of strictures was stable, there was a significant increase in the predilation esophageal diameter (from 13.9 to 16.0 mm; P < .001). Global symptom improvement was reported in 91% (P < .001).
In this population of severe, refractory, and fibrostenotic EoE patients, most achieved histologic, endoscopic, and symptom improvement with a median of 6 months of dupilumab, and esophageal stricture diameter improved. Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials.
Endoscopic Ultrasound Can Measure Esophageal Remodeling in Eosinophilic Esophagitis
2024, Techniques and Innovations in Gastrointestinal Endoscopy
Although esophageal widening is a normal consequence of growth in pediatric individuals, esophageal remodeling plays a major role in the morbidity of pediatric and adult eosinophilic esophagitis (EoE). However, the disease is defined by esophageal dysfunction and mucosal eosinophilia. One potential explanation is the difficulty in quantitating remodeling.
This prospective, IRB-approved longitudinal study evaluated endoscopic ultrasound (EUS) in 78 children, adolescents, and young adults referred to a single academic medical center for esophageal indications. Patients with proven EoE had serial EUS exams that measured total wall thickness (TWT) and esophageal wall sublayers during routine endoscopies to manage their disease. Student t tests and mixed linear models were employed to compare groups.
TWTs from the distal (2.3 ± 0.5 vs 1.7 ± 0.3, P < .01) and mid esophagus (2.1 ± 0.5 vs 1.6 ± 0.3, P < .05) were increased in active EoE patients > 10 years of age compared with similarly aged controls. After achieving clinical and histologic remission, their TWTs were significantly decreased (distal: 1.9 ± 0.4 vs 2.3 ± 0.5, P < .05; mid: 1.7 ± 0.4 vs 2.1 ± 0.5, P < .05). Mixed linear models further demonstrated that during active EoE, TWTs, esophageal muscle layers, and the mucosa and submucosa were thickened in older adolescents at both sites (P < .05 for each). In remission, TWTs returned to control values.
This pilot study demonstrates that EUS, a unique application of point-of-care ultrasound, can identify the esophageal remodeling that occurs in older adolescents with active EoE. Furthermore, EUS has defined this remodeling as a transmural phenomenon that occurs in the mid and distal esophagus and can completely reverse with adequate treatment.
Higher Body Mass Index Is Associated With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis
2023, Clinical Gastroenterology and Hepatology
Understanding which eosinophilic esophagitis (EoE) patients will respond to treatment with topical corticosteroids (tCS) remains challenging, and it is unknown whether obesity impacts treatment response. This study aimed to determine whether treatment outcomes to tCS in EoE patients vary by body mass index (BMI).
This retrospective cohort study of the University of North Carolina EoE Clinicopathologic database assessed subjects age 14 years or older with a new diagnosis of EoE. Their BMI was calculated and histologic, symptom, and endoscopic responses were recorded after tCS treatment. The treatment response of obese (BMI, ≥30 kg/m²) and nonobese EoE status was compared using bivariate and multivariate analyses.
We identified 296 EoE patients treated with tCS. Baseline characteristics were similar, although obese EoE patients had more heartburn and hiatal hernias. Histologic response was higher for those who were nonobese compared with obese at fewer than 15 (61% vs 47%; P = .049) and 6 or fewer (54% vs 38%; P = .02) eosinophils per high-power field, respectively. In addition, nonobese patients had significantly greater endoscopic and symptomatic responses. On multivariate analysis, increasing BMI was associated independently with decreased histologic response after accounting for age, heartburn, dilation, and hiatal hernia whether BMI was assessed as a continuous variable (adjusted odds ratio [aOR], 0.93; 95% CI, 0.89–0.98), as nonobese vs obese (aOR, 0.38; 95% CI, 0.21–0.68), or in 4 categories (overweight vs normal [aOR, 0.46; 95% CI, 0.26–0.84] or obese vs normal [aOR, 0.26; 95% CI, 0.13–0.51]).
As BMI increases in EoE patients, the odds of histologic, symptomatic, and endoscopic responses to tCS decreases, with obese patients having an approximately 40% decrease in odds of response.
Development of a Practical Guide to Implement and Monitor Diet Therapy for Eosinophilic Esophagitis
2023, Clinical Gastroenterology and Hepatology
Dietary therapy for short- and long-term management of eosinophilic esophagitis is an effective yet poorly understood and underutilized treatment strategy. Despite several prospective trials demonstrating the efficacy of dietary therapies, successful clinical implementation is hampered by the need for a multidisciplinary approach including dietitian support and provider expertise. The availability of these resources is not readily available to most gastroenterologists. Without standardized guidance on starting or completing the diet for gastrointestinal providers and/or consulting dietitians, provider attitudes toward dietary therapy vary greatly depending on familiarity and knowledge gaps in using diet therapy. This review aims to summarize evidence in support of dietary therapy in eosinophilic esophagitis while providing guidance on initiation and implementation of dietary therapy for providers.
Eosinophilic Esophagitis: A Review for the Primary Care Practitioner
2023, Primary Care - Clinics in Office Practice
A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions
2022, Journal of Allergy and Clinical Immunology
Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE.
A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity.
Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system—the Index of Severity for Eosinophilic Esophagitis (I-SEE)—that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE.
A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated “I-SEE” to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.

View all citing articles on Scopus

: Conflicts of interest The authors disclose the following: E.S.D. has received research funding from AstraZeneca and Meritage and is a consultant for Aptalis, Novartis, Receptos, and Regeneron. C.A.L. is a member of the speaker bureau for Abbott Nutrition.

: Funding Supported in part by National Institutes of Health grant K23DK090073 (to E.S.D.).

: Author names in bold designate shared co-first authorship.

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Reviews and PerspectivesReviews in Basic and Clinical Gastroenterology and HepatologyAdvances in Clinical Management of Eosinophilic Esophagitis

Section snippets

Definition

Features in Children

Challenges

Epidemiology

Treatment

Emerging Concepts and Unresolved Issues

Conclusions

Gastroenterology

J Allergy Clin Immunol

Gastroenterology

Gastroenterology

Clin Gastroenterol Hepatol

J Allergy Clin Immunol

J Allergy Clin Immunol

Gastrointest Endosc Clin North Am

J Allergy Clin Immunol

Gastrointest Endosc

Gastroenterology

Gastrointest Endosc

Clin Gastroenterol Hepatol

Gastroenterology

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

Gastrointest Endosc Clin North Am

J Allergy Clin Immunol

Gastroenterology

Gastrointest Endosc

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

J Pediatr

Ann Allergy Asthma Immunol

Clin Gastroenterol Hepatol

Gastrointest Endosc

Gastroenterology

J Allergy Clin Immunol

Gastroenterology

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

Gastroenterology

Gastroenterol Clin North Am

Gastroenterology

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

J Allergy Clin Immunol

Gastroenterology

ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis

Am J Gastroenterol

Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome

Dig Dis Sci

Idiopathic eosinophilic esophagitis: a frequently overlooked disease with typical clinical aspects and discrete endoscopic findings

Schweiz Med Wochenschr

Variability in diagnostic criteria for eosinophilic esophagitis: a systematic review

Am J Gastroenterol

Eosinophilic esophagitis: a subset of eosinophilic gastroenteritis

Curr Gastroenterol Rep

Eosinophilic esophagitis

N Engl J Med

14 years of eosinophilic esophagitis: clinical features and prognosis

J Pediatr Gastroenterol Nutr

Reviews and Perspectives
Reviews in Basic and Clinical Gastroenterology and Hepatology
Advances in Clinical Management of Eosinophilic Esophagitis