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Korean J Helicobacter  Up Gastrointest Res > Volume 25(2); 2025 > Article
Choi: Eosinophilic Esophagitis: Emerging Insights Into Diagnosis and Management

Abstract

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated, esophageal disease characterized by eosinophilic infiltration and symptoms such as dysphagia, food impaction, and esophageal dysfunction. Advances in diagnostic tools, including the EoE Endoscopic Reference Score and the Eosinophilic Esophagitis Histologic Scoring System, have improved disease characterization and monitoring. First-line treatments, such as proton pump inhibitors and topical corticosteroids, achieve significant histological and clinical remission rates. Dietary approaches, including the six-food elimination diet and step-up strategies, provide effective non-pharmacological options, although adherence remains a challenge. Esophageal dilation is a safe and effective therapy for relieving symptoms of dysphagia caused by strictures. Emerging biological therapies, such as dupilumab, show promise for targeting specific inflammatory pathways and addressing refractory cases. Although current therapies have demonstrated efficacy, gaps remain in the optimization of long-term disease control and treatment sequencing.

INTRODUCTION

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated, antigen-driven disease confined to the esophagus, and its global prevalence has been rising in recent years [1]. It is characterized by a T helper 2 cell (Th2)-mediated immune response, with food antigens recognized as the primary triggers [2]. The pathophysiological mechanisms underlying EoE, including Th2-driven inflammation, epithelial barrier dysfunction, and eosinophilic infiltration, are illustrated in Fig. 1 [3]. Although EoE affects only the esophagus, similar pathologies involving the stomach or small intestine are classified as eosinophilic gastroenteritis or enteritis, respectively. EoE is more commonly diagnosed in Western populations, whereas its prevalence in Asia remains low. However, recent studies in South Korea have revealed a trend toward increasing prevalence [4-8].
This review of the recent literature provides a comprehensive summary of the latest insights on the definition and diagnosis of EoE to help clinicians effectively manage patients with this condition.

DEFINITION OF EoE

EoE is a chronic disorder characterized by esophageal symptoms and histological eosinophilic infiltration. A diagnosis requires fulfillment of the following criteria: the presence of esophageal dysfunction symptoms, such as dysphagia, food impaction, and heartburn; histological evidence of ≥15 eosinophils per high-power field in esophageal biopsy specimens; and exclusion of other potential causes of esophageal eosinophilia, including gastroesophageal reflux disease (GERD), infection, drug reaction, connective tissue disease, and eosinophilic gastroenteritis [1,9-11]. Historically, the first consensus diagnostic criteria were introduced in 2007, defining EoE as a clinicopathologic condition requiring both histologic and clinical features for diagnosis [12]. In 2011, proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) was classified as a distinct entity, separate from EoE, leading to the exclusion of an EoE diagnosis in patients showing clinical and histological improvement with PPI therapy [13]. However, subsequent studies revealed that PPIs not only suppress gastric acid but also inhibit Th2-mediated inflammatory pathways, thereby reducing eosinophilic infiltration. This led to the discontinuation of the PPIREE concept, which is now recognized as a phenotype of EoE. According to the 2018 international consensus guidelines [14], a response to PPI therapy is no longer used as an exclusion criterion for EoE; PPI therapy has become an integral part of both the diagnostic and therapeutic approaches for this condition [15].

CLINICAL MANIFESTATIONS OF EoE

The clinical manifestations of EoE vary depending on the patient’s age, disease progression, and stage of inflammation or fibrosis [9,10,12,16-19]. In pediatric patients, the inflammatory pathophysiology characteristic of the early stages of EoE is prominent, and is often referred to as the inflammatory phenotype. Symptoms are generally nonspecific and inflammation-dominant, commonly including vomiting, abdominal pain, poor appetite, growth retardation, and failure to thrive. Feeding difficulties and reflux-like symptoms are prominent in infants, whereas behaviors such as refusal of solid foods and prolonged eating times are observed in school-aged children. These nonspecific symptoms frequently lead to delayed diagnoses.
In contrast, adult patients typically present with dysphagia and food impaction as primary symptoms. Persistent esophageal inflammation in adults often leads to fibrosis and stricture formation (the fibrostenotic phenotype). Symptoms such as chest pain or reflux symptoms that are unresponsive to PPI therapy may also be observed. Many adults develop compensatory behaviors, such as eating slowly or frequently drinking water to alleviate their symptoms.
The clinical presentation of symptoms varies depending on the stage of disease progression. During the early inflammatory phase, vomiting, abdominal pain, and reflux-like symptoms are commonly observed, particularly in pediatric patients. As the fibrosis progresses, structural complications, such as the strictures and dysphagia frequently seen in adults, may develop. Approximately 50%–70% of patients with EoE have comorbid atopic diseases, such as asthma, allergic rhinitis, or atopic dermatitis, which can serve as important diagnostic clues [1,9,17-19]. A thorough evaluation of the patient’s symptoms and medical history, with close attention to compensatory eating behaviors and changes in symptom patterns, is essential for the early diagnosis and effective management of this disease.

DIAGNOSIS OF EoE

Endoscopy

Endoscopy and biopsy are essential tools for diagnosing EoE [11,20,21]. The key endoscopic findings include edema, characterized by mucosal thickening with loss of the vascular pattern; trachealization, which involves the formation of rings (concentric structures in the esophageal wall) that may persist despite treatment in patients with advanced fibrosis; exudates presenting as whitish spots on the mucosal surface, suggestive of eosinophilic microabscesses; furrows that are longitudinal linear grooves along the esophageal mucosa; and strictures, defined as luminal narrowing resulting from advanced fibrosis. These findings can be evaluated using the edema, rings, exudates, furrows, and strictures (EREFS) system, which is widely used to assess disease severity and monitor treatment response (Table 1) [22]. Although endoscopic severity does not always directly correlate with histological severity, studies have shown that EREFS score improvements are associated with histological remission following treatment. Importantly, approximately 17% of patients with EoE may exhibit normal endoscopic findings [9]. This makes esophageal biopsies essential in symptomatic patients, such as those with dysphagia or food impaction, regardless of the endoscopic appearance. During endoscopy, at least six biopsy samples should be obtained from two or more sites, including the proximal and distal esophagus [10,23,24]. Additional biopsies from the mid-esophagus may improve the diagnostic yield because eosinophilic infiltration often shows a patchy distribution across the esophagus [9].

Histology

The histological hallmark of EoE is a significantly increased eosinophil density in the esophageal epithelium, with a diagnostic threshold of ≥15 eosinophils per high-power field in at least one esophageal biopsy specimen. This criterion demonstrates high sensitivity (100%) and specificity (96%) for diagnosing EoE [25]. However, focusing exclusively on eosinophil density may overlook other critical histological markers, such as basal cell hyperplasia, eosinophil microabscesses, eosinophil degranulation, and lamina propria fibrosis. Additional features, including dilated intercellular spaces and rete-peg elongation, contribute to the comprehensive characterization of EoE and help differentiate it from other conditions such as GERD.
Efforts to standardize the assessment of histological changes in EoE have led to the development of tools such as the Eosinophilic Esophagitis Histological Scoring System (EoEHSS) [2,9,11,26,27]. This scoring system evaluates eight key histological features of EoE, including eosinophilic inflammation, basal zone hyperplasia, and fibrosis, by assigning scores for both severity and extent. Studies have demonstrated that the EoEHSS exhibits high intra- and inter-rater reliabilities and is sensitive to changes following treatment, making it a valuable tool in clinical trials.

OTHER METHODS OF DIAGNOSIS

Esophagography

Esophagography is a valuable diagnostic tool for evaluating structural abnormalities in EoE, such as the presence of strictures and a narrow-caliber esophagus [2,9-11,28]. It is particularly effective for identifying strictures <15 mm in diameter, for which endoscopy has low sensitivity. Studies have indicated that esophagography can detect strictures missed by endoscopy in up to 50% of pediatric cases [29]. Additionally, it plays a key role in guiding treatment strategies, including esophageal dilation. Although esophagography does not reliably detect mucosal abnormalities and lacks standardized protocols for measuring esophageal diameters, it remains crucial for assessing fibrotic complications and informing individualized treatment approaches for patients with EoE.

Functional lumen imaging probe

A functional lumen imaging probe (FLIP) is a diagnostic tool that utilizes high-resolution impedance planimetry to evaluate esophageal geometry and wall distensibility in real time [2,9,10,28]. By measuring the esophageal diameter and wall stiffness during progressive volume distension, FLIP is particularly effective for detecting fibrostenotic manifestations of EoE, such as subtle strictures and a narrow-caliber esophagus. Unlike traditional endoscopy and esophagography, FLIP uniquely predicts the risk of food impaction. A prospective study involving 70 patients with EoE demonstrated that reduced esophageal distensibility was correlated with a greater need for dilation and an increased risk of food impaction [30]. Additionally, FLIP has been shown to provide valuable insights into disease activity, correlating more closely with clinical symptoms than histology. Recent studies have expanded the role of FLIP in characterizing the biomechanics of EoE. A 2023 study by a Chicago group introduced a novel physiomechanical classification of EoE, identifying seven distinct subtypes based on FLIP parameters [31]. This classification demonstrated significant correlation with symptom duration, endoscopic findings, and treatment responses, suggesting its potential for guiding therapeutic decisions. Another study from 2022 underscored the relationship between esophageal dysmotility and fibrostenotic disease severity in patients with EoE [32]. The findings indicated that FLIP-detected abnormal contractile responses were more frequently associated with reduced esophageal distensibility and more severe endoscopic ring scores, whereas mucosal eosinophilia alone did not predict dysmotility. The effectiveness of FLIP for monitoring therapeutic responses has also been documented, with improvements in distensibility observed after steroid treatment. Although its availability is limited, FLIP provides real-time data to guide therapeutic decisions, such as the need for dilation, and serves as a valuable metric for assessing persistent symptoms in patients undergoing optimal therapy.

Mucosal impedance

Mucosal impedance (MI) is a diagnostic tool that measures the integrity of the esophageal epithelial barrier and has been proposed to distinguish EoE from GERD, two conditions with overlapping clinical presentations [2,10,11]. MI is assessed using a specialized balloon catheter or an endoscopic impedance probe, with measurements inversely related to barrier dysfunction. Patients with EoE typically exhibit uniformly low MI throughout the esophagus or patchy distribution, whereas those with GERD are characterized by low MI in the distal esophagus, which normalizes proximally. Studies have demonstrated the high sensitivity (90%) and specificity (91%) of MI for identifying EoE, highlighting its potential as a noninvasive assessment tool [33]. However, MI is not yet widely available, and whether MI measurements can replace esophageal biopsies in routine clinical practice remains unclear.

High-resolution manometry

High-resolution manometry (HRM) is a valuable tool for evaluating esophageal motility and is recommended for patients with EoE who continue to experience symptoms despite histological remission and the absence of esophageal strictures [9,10,28]. Eosinophilic inflammation can disrupt esophageal motility through various mechanisms, leading to a range of motility disorders. Studies have revealed inconsistent motility patterns in patients with EoE, including ineffective or fragmented peristalsis, esophagogastric junction outflow obstruction, and, in rare cases, achalasia. A recent meta-analysis by Reddy et al. [34] analyzed esophageal dysmotility in patients with EoE using HRM, and found that 53% exhibited motility abnormalities, primarily minor peristaltic disorders such as ineffective esophageal motility and fragmented peristalsis. However, major motility disorders were rare, suggesting that EoErelated dysmotility may result from both inflammatory and fibrotic mechanisms rather than direct eosinophilic infiltration. These findings highlight the potential role of HRM in assessing persistent dysphagia despite histological or endoscopic remission. In a prospective study of 35 patients with EoE, 57% had normal HRM findings; in a larger multicenter cohort, 38% exhibited motility abnormalities, such as hypo- or hypercontractile disorders [33]. Although HRM findings are not specific to EoE, the test provides critical insights into esophageal dysmotility, which may contribute to symptoms such as dysphagia and chest pain [34]. Integrating HRM data with other diagnostic approaches enhances the comprehensive evaluation and management of EoE.

Minimally invasive esophageal sampling techniques

Minimally invasive esophageal sampling techniques are emerging as potential alternatives to traditional endoscopy examinations for diagnosing EoE. These methods aim to reduce the risks, costs, and inconveniences associated with standard endoscopy while maintaining diagnostic accuracy. Transnasal endoscopy is an office-based procedure that eliminates the need for sedation while providing direct visualization of the esophageal mucosa [9,11]. A study involving 22 children with EoE demonstrated high patient and parent preferences for this method, with biopsy specimens comparable in quality to those obtained via traditional endoscopy [35]. Similarly, a cytosponge assessment involves swallowing a gelatin capsule containing a compressed mesh that collects tissue samples when withdrawn [11]. In a pilot study of 20 patients, cytosponges were useful for identifying active EoE in 83% of cases and was preferred over endoscopy [36]. Finally, the esophageal string test collects esophageal secretions for analysis and was shown to distinguish active EoE from other conditions in a study of 41 children [11,37]. This test is well-tolerated and does not require anesthesia.
Although largely experimental, these innovative methods show significant promise for reducing the burden of multiple endoscopies in EoE management. They provide reliable sampling with high patient acceptance, particularly in pediatric populations. However, further research is needed to validate their utility across broader patient demographics and to integrate them into routine clinical practice [2].

TREATMENT

Proton pump inhibitors

PPIs are recommended as a first-line treatment for EoE and have proven effective for inducing both histological and clinical remission [1,9,11,19,38-40]. They reduce antigen exposure in the esophageal mucosa by suppressing gastric acid secretion. Additionally, they inhibit the Th2 cytokine pathway and downregulate eotaxin-3 expression, thereby mitigating eosinophilic inflammation. A meta-analysis of 33 predominantly small retrospective case series, involving 431 adults and 188 children, revealed partial clinical response rates of 60.8% and histologic response rates of 50.5% [41]. However, heterogeneity in study designs, dosing regimens, and remission definitions posed challenges for direct comparisons across studies. A more recent cross-sectional study based on the European registry (554 adults and 76 children) demonstrated a histological response in 48.8% of patients and a clinical response in 71.0% [9,42]. Notably, patients with inflammatory phenotypes exhibited higher response rates than did those with fibrostenotic disease. Patients prescribed high-dose PPI therapy (e.g., 20 mg omeprazole, twice daily) achieved a clinicopathological response rate of 50.8%, compared with only 35.8% in patients receiving standard- or lowdose regimens. An analysis of remission induction based on treatment duration showed that 8–10 weeks of therapy yielded a response rate of 50.4%, whereas extending the treatment beyond 10–12 weeks resulted in a response rate of 65.2%. Thus, a minimum treatment duration of 8–12 weeks of twice-daily PPI therapy is recommended before assessing the histologic response [9]. PPIs are also effective in maintaining remission in patients who achieve histologic responses. In one study, the long-term remission rate was 81% among patients who initially responded to PPI therapy [43]. Another study involving 630 patients treated with PPIs showed that 172 received maintenance therapy; among 103 patients with complete clinical and histologic follow-up data, 69.9% achieved sustained clinicopathologic remission [42]. Although further research is needed, the current evidence highlights the pivotal role of PPIs in both inducing and maintaining remission in patients with EoE.

Topical corticosteroids

Topical corticosteroids (TCS) are effective in improving symptoms and achieving histologic remission in patients with EoE [2,9,10,18,28,38-40]. A meta-analysis and systematic review of at least 11 randomized controlled trials demonstrated the efficacy of TCS. A large meta-analysis reported an odds ratio of 13.66 (95% confidence interval: 2.65–70.34) for histologic remission [44]. One study showed that treatment with fluticasone (880 μg, twice daily) resulted in a histologic remission rate of 62%, compared with 0% in the placebo group [45]. The budesonide orally disintegrating tablet (BOT), approved in Europe, is recommended for adult patients. Viscous budesonide demonstrated a higher histologic remission rate than did fluticasone (64% vs. 27%) [46]. Moreover, patients treated with BOTs achieved histologic remission rates of 57.6% at 6 weeks and 84.7% at 12 weeks [47]. The most commonly reported adverse effect is esophageal candidiasis, which is generally mild and rarely severe. Although long-term data are limited, TCS has shown efficacy and safety as a maintenance therapy. In a study examining 48 weeks of maintenance therapy with BOT, 73.5% of patients in the 0.5-mg twice-daily group and 75.0% in the 1.0-mg twice-daily group maintained remission, compared with only 4.4% in the placebo group [48].
In the United States, a budesonide oral suspension was approved by the U.S. Food and Drug Administration for EoE treatment in February 2024. Traditional inhaled corticosteroids, originally designed for asthma treatment, are less effective against EoE because of the inadequate esophageal contact time. In contrast, European guidelines recommend avoiding off-label corticosteroids when EoE-specific formulations are available [2]. Recent advancements include the development of novel formulations, such as orally disintegrating tablets and premixed suspensions, aimed at improving patient adherence and ease of use [28]. These innovations are expected to expand the treatment options for patients with EoE in the near future.

Dietary therapy

Dietary therapy reduces eosinophilic inflammation by eliminating specific antigens and is a valuable approach for patients seeking to avoid pharmacological treatment. The primary dietary strategies for managing EoE include the empiric elimination, elemental, and allergy testing–directed elimination diets. The six-food (milk, wheat, eggs, soy, peanuts/tree nuts, and seafood) elimination diet (SFED) has been demonstrated to achieve histologic remission rates of approximately 65%– 80% [2,9,11,17,19,28,38-40]. However, a recent randomized trial found that SFED led to histologic remission in 40% of patients after six weeks, which was not significantly different from the 34% remission rate achieved with a one-food (milk, only) elimination diet [49]. These findings suggest that a step-up dietary approach that starts with a less restrictive diet and escalates only if necessary may improve adherence while maintaining effectiveness. To address these limitations, simplified alternatives diets have been developed, including the two-(TFED) and four-food (FFED) elimination diets that target major allergens, including milk and wheat. These approaches achieve histological remission rates of approximately 40%–50% and are considered more practical for clinical use. A step-up strategy, beginning with a TFED and escalating to an FFED or SFED, if needed, has been shown to reduce the burden of dietary restrictions and endoscopic monitoring while maintaining therapeutic efficacy. An elemental diet achieves high histological remission rates (>90%); however, its poor palatability, high cost, and, in some cases, the need for enteral feeding limit its use. It is typically reserved for patients who do not respond to other dietary therapies or as an adjunctive treatment. The allergy testing-directed elimination diet, based on the theory that removing allergens identified through standard allergy testing can effectively treat EoE, has demonstrated low reliability and is generally less effective than empiric elimination diets.
Although dietary therapy can maintain long-term remission by addressing underlying triggers, adherence rates decline over time. Additionally, dietary therapy poses the risk of nutritional deficiencies, particularly in pediatric patients or those with preexisting dietary restrictions. Therefore, dietitian-led guidance is essential for educating patients on alternative food options and ensuring nutritional balance [9,40]. A multidisciplinary approach involving experienced dietitians, clinicians, and allergists is strongly recommended to optimize treatment outcomes and minimize risks. Although combining dietary therapy with pharmacological treatment is not routinely recommended, it may benefit patients who fail monotherapy [9,28].

Endoscopic treatment

Esophageal dilation is a safe and effective therapeutic option for the management of dysphagia caused by strictures in patients with EoE. Studies have reported symptom improvement in 85%–95% of patients, with serious complications (e.g., perforations) occurring at a low rate (0.033%–0.610%) [11,38-40]. Both bougie and balloon dilation techniques have proven effective, and newer devices (e.g., the BougieCap) have also been demonstrated to be safe [40,50]. However, although esophageal dilation effectively relieves symptoms, it does not target the underlying inflammatory process. Consequently, combining dilation with anti-inflammatory therapy is crucial for minimizing the need for repeated interventions.
Because endoscopy may underestimate the presence of strictures, adjunctive diagnostic tools (e.g., EndoFLIP or esophagography) are recommended [9,40]. Empirical dilation may be considered for patients with histologic remission who continue to experience dysphagia despite the absence of visible strictures. For optimal outcomes, esophageal dilation should be personalized to the patient’s specific needs and integrated with pharmacological or dietary therapy as part of a comprehensive management plan for EoE.

Dupilumab

Dupilumab, a fully human monoclonal antibody, targets the interleukin (IL)-4 receptor alpha subunit to inhibit IL-4 and IL-13 signaling, key drivers of type 2 inflammation in EoE [28,40,51]. It is approved for patients aged 12 years and older, with recent approval extended to children aged 1 to 11 years [28]. Clinical trials have demonstrated its efficacy at a weekly dosage of 300 mg, with histologic remission rates of 60% compared with 5%–6% for placebo-treated patients [51]. Additionally, dupilumab has been shown to significantly improve Dysphagia Symptom Questionnaire scores. In patients aged 1–11 years, similar benefits in histological remission have been observed [52]. Side effects are generally mild, including injection site reactions and, less commonly, conjunctivitis and skin infections; serious adverse events are rare.
Dupilumab is particularly effective in patients with PPI-refractory EoE or those intolerant to other therapies, such as topical steroids or elimination diets. In cases involving comorbid type 2 inflammatory diseases, such as asthma or atopic dermatitis, dupilumab can serve as a dual-purpose treatment by addressing both EoE and associated conditions. Although often considered a second-line therapy, dupilumab can be used as a first-line option in select patients, i.e., those with severe symptoms or high comorbidity burdens [28,53]. Long-term trials and real-world studies continue to validate its safety and efficacy, reinforcing its role as a transformative option in EoE management. A summary of the currently available therapeutic options for EoE, including their mechanisms of action and recommended uses, is provided in Table 2.

Investigational treatments

The emerging therapies for EoE include several biological treatments that target specific inflammatory pathways. Cendakimab, an anti-IL-13 monoclonal antibody, has shown promise in phase II trials, demonstrating significant reductions in esophageal eosinophil counts, endoscopic severity, and dysphagia scores [54]. Phase III trials are ongoing to evaluate its efficacy in inducing and maintaining remission in both adults and adolescents [28]. Mepolizumab and reslizumab, anti-IL-5 therapies, have shown reduced eosinophil counts but have failed to improve clinical symptoms or histologic remission [40]. Similarly, benralizumab, which depletes eosinophils through IL-5 receptor activation, achieved high histologic response rates (>80%) but failed to improve symptoms, suggesting that targeting eosinophils alone may not address the complex pathogenesis of EoE [55]. Other investigational therapies include tezepelumab, a thymic stromal lymphopoietin-targeting monoclonal antibody already approved for asthma; this drug is now in phase III trials for EoE [40]. By contrast, omalizumab (anti-immunoglobulin E) and infliximab (anti-tumor necrosis factor) have not shown efficacy in clinical trials [2,9,28,39,40]. Additionally, cromolyn sodium and montelukast have not demonstrated meaningful benefits, with response rates comparable to those associated with placebo treatment. Vedolizumab, an anti-integrin antibody, has shown EoE management potential in two case reports, particularly in patients with concurrent inflammatory bowel disease [9,28]. Novel agents, such as sphingosine-1-phosphate receptor modulators and immunomodulatory chaperone proteins, have yielded promising results in phase II trials, highlighting their potential for future studies [28]. These findings reflect the evolving therapeutic landscape of EoE but emphasize the need for further research and validation to establish their roles in clinical practice.

CONCLUSION

EoE is a multifaceted disease that requires a comprehensive and individualized approach for diagnosis and management. Advances in diagnostic tools, such as the EREFS and EoEHSS, have significantly improved the assessment and monitoring of disease activity. Therapeutic strategies, including PPIs, TCS, and dietary elimination approaches, have demonstrated efficacy in achieving both clinical and histological remission. Emerging biological therapies (e.g., dupilumab) show promise for addressing refractory cases by targeting specific inflammatory pathways; they also offer the potential for more personalized treatment options. Despite these advancements, critical gaps remain in optimizing long-term disease control, determining the optimal therapeutic sequence, and integrating novel treatments into routine clinical practice. A thorough understanding of the clinical features, diagnostic criteria, and firstline therapies for EoE is essential for mitigating the long-term complications associated with persistent inflammation.

Notes

Availability of Data and Material

Data sharing not applicable to this article as no datasets were generated or analyzed during the study.

Conflicts of Interest

Hyun Ho Choi, a contributing editor of the Korean Journal of Helicobacter and Upper Gastrointestinal Research, was not involved in the editorial evaluation or decision to publish this article.

Funding Statement

None

Acknowledgements

None

Fig. 1.
Pathophysiological mechanisms of eosinophilic esophagitis. Exposure to food allergens and immune adjuvants (including microbial dysbiosis) triggers the release of alarmins, including TSLP and IL-13, from the esophageal epithelium. These cytokines activate Th2, which subsequently produce IL-4, IL-5, and IL-13, driving a cascade of inflammatory responses. IL-4 and IL-13 contribute to epithelial barrier dysfunction by inducing dilated intracellular spaces and disrupting epithelial integrity. CXCL16 expression facilitates the recruitment of iNKT cells, reinforcing Th2-driven inflammation. IL-5 promotes the recruitment and activation of eosinophils, leading to the release of MBP and TNF, which contribute to tissue damage and fibrosis. Additionally, mast cells and basophils become activated, further amplifying inflammation and promoting fibrotic remodeling through TGF-β. These processes collectively contribute to chronic esophageal inflammation, tissue remodeling, and clinical manifestations (e.g., dysphagia and stricture formation). Adapted from Zhang et al. Front Cell Infect Microbiol 2023;13:1206343. [3], under the terms of the Creative Commons License (CC BY). TSLP, thymic stromal lymphopoietin; IL, interleukin; Th2, T helper 2 cell; CXCL16, CXC chemokine motif ligand 16; iNKT, invariant natural killer T; MBP, major basic protein; TNF, tumor necrosis factor; TGF-β, transforming growth factor-beta; TLRs, toll-like receptors.
kjhugr-2025-0013f1.jpg
Table 1.
Eosinophilic Esophagitis Endoscopic Reference Score System
Feature Grade 0 (none) Grade 1 (mild) Grade 2 (moderate) Grade 3 (severe)
Edema Normal vascular pattern Loss of vascular markings Diffuse edema
Rings None Subtle concentric ridges Distinct rings (permit passage of an endoscope) Distinct rings (do not permit passage of an endoscope)
Exudates None <10% esophageal surface involvement >10% esophageal surface involvement
Furrows None Presence of longitudinal furrows Deep, extensive furrows
Stricture None Present
Table 2.
Therapeutic options for eosinophilic esophagitis
Treatment Mechanism of action Efficacy Limitations
Proton pump inhibitors Suppress gastric acid secretion; inhibit Th2 cytokine signaling and eotaxin-3 expression Histologic remission approximately 50%, clinical response Variability in response, not FDA- approved specifically for EoE
Topical corticosteroids Local anti-inflammatory effect; reduces eosinophil infiltration approximately 60% to 70% High histologic remission (60%–80%) Risk of esophageal candidiasis, relapse upon withdrawal
Dietary therapy (elimination & elemental diets) Remove food allergens or replace with amino-acid formula to reduce antigen-driven eosinophilic inflammation SFED: approximately 40% to 80% remission, FFED: approximately 50%, TFED: approximately 40%, elemental diet: >90% remission Requires multiple endoscopies, risk of nutritional deficiencies, elemental diet has poor palatability and high cost
Biologic therapy (dupilumab, cendakimab, etc.) Target Th2 cytokines (IL-4, IL-5, IL-13) to reduce eosinophilic inflammation Varies by target pathway Expensive, limited long-term data, not widely available
Esophageal dilation Mechanically widens strictures to improve swallowing Symptom relief in fibrostenotic EoE (85%–95%) Does not treat underlying inflammation, requires repeated procedures

Th2, T helper 2 cells; IL, interleukin; SFED, six-food elimination diet; FFED, four-food elimination diet; TFED, two-food elimination diet; EoE, eosinophilic esophagitis; FDA, U.S. Food and Drug Administration.

REFERENCES

1. Furuta GT, Katzka DA. Eosinophilic esophagitis. N Engl J Med 2015;373:1640–1648.
crossref pmid pmc
2. Fernandez-Becker NQ. Eosinophilic esophagitis: incidence, diagnosis, management, and future directions. Gastroenterol Clin North Am 2021;50:825–841.
pmid
3. Zhang X, Zhang N, Wang Z. Eosinophilic esophagitis and esophageal microbiota. Front Cell Infect Microbiol 2023;13:1206343.
crossref pmid pmc
4. Yang EJ, Jung KW. Role of endoscopy in eosinophilic esophagitis. Clin Endosc 2025;58:1–9.
crossref pmid pmc pdf
5. Kim GH, Jung KW, Jung HY, et al. Diagnostic trends and clinical characteristics of eosinophilic esophagitis: a Korean, single-center database study. J Neurogastroenterol Motil 2018;24:248–254.
crossref pmid pmc
6. Kim GH, Park YS, Jung KW, et al. An increasing trend of eosinophilic esophagitis in Korea and the clinical implication of the biomarkers to determine disease activity and treatment response in eosinophilic esophagitis. J Neurogastroenterol Motil 2019;25:525–533.
crossref pmid pmc
7. Chang YH, Shin CM, Lee DH, Yoon H, Park YS, Kim N. Association between Helicobacter pylori infection and eosinophilic esophagitis. Korean J Gastroenterol 2023;82:122–126.
crossref pmid
8. Kim SJ, Park MI, Kim GH, et al. Practice patterns for eosinophilic esophagitis patients in Busan and Gyeongnam: a Korean multicenter database study. J Neurogastroenterol Motil 2021;27:71–77.
crossref pmid pmc
9. Dhar A, Haboubi HN, Attwood SE, et al. British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut 2022;71:1459–1487.
crossref pmid pmc
10. de Bortoli N, Visaggi P, Penagini R, et al. The 1st EoETALY consensus on the diagnosis and management of eosinophilic esophagitis - definition, clinical presentation and diagnosis. Dig Liver Dis 2024;56:951–963.
crossref pmid
11. Straumann A, Katzka DA. Diagnosis and treatment of eosinophilic esophagitis. Gastroenterology 2018;154:346–359.
crossref pmid
12. Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007;133:1342–1363.
crossref pmid
13. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011;128:3–20.e6; quiz 21-22.
pmid
14. Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis: proceedings of the AGREE conference. Gastroenterology 2018;155:1022–1033.e10.
pmid
15. Nonevski IT, Myburgh SJ. Eosinophilic esophagitis for the advanced practice provider. iGIE 2023;2:575–580.
crossref
16. Schoepfer AM, Safroneeva E, Bussmann C, et al. Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology 2013;145:1230–1236.e2.
crossref pmid
17. Kim SJ, Choi CW, Hwang CS. Diagnosis and treatment of eosinophilic esophagitis. Korean J Gastroenterol 2022;79:99–108.
crossref pmid
18. Lee H. Clinical review of eosinophilic esophagitis. Korean J Helicobacter Up Gastrointest Res 2018;18:3–12.
crossref pdf
19. 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;5:335–358.
pmid pmc
20. Falk GW. Top tips for high-quality endoscopy in eosinophilic esophagitis. Gastrointest Endosc 2023;98:237–240.
crossref pmid
21. Dellon ES, Khoury P, Muir AB, et al. A clinical severity index for eosinophilic esophagitis: development, consensus, and future directions. Gastroenterology 2022;163:59–76.
crossref pmid pmc
22. Hirano I, Moy N, Heckman MG, Thomas CS, Gonsalves N, Achem SR. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut 2013;62:489–495.
crossref pmid
23. Dellon ES, Muir AB, Katzka DA, et al. ACG clinical guideline: diagnosis and management of eosinophilic esophagitis. Am J Gastroenterol 2025;120:31–59.
crossref pmid
24. Aceves SS, Alexander JA, Baron TH, et al. Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy consensus conference. Gastrointest Endosc 2022;96:576–592.e1.
crossref pmid
25. Dellon ES, Speck O, Woodward K, et al. Distribution and variability of esophageal eosinophilia in patients undergoing upper endoscopy. Mod Pathol 2015;28:383–390.
crossref pmid pmc pdf
26. Collins MH, Martin LJ, Alexander ES, et al. Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Dis Esophagus 2017;30:1–8.
crossref pmid pmc
27. Ma C, Jairath V, Feagan BG, et al. Responsiveness of a histologic scoring system compared with peak eosinophil count in eosinophilic esophagitis. Am J Gastroenterol 2022;117:264–271.
crossref pmid
28. Alsohaibani FI, Peedikayil MC, Alzahrani MA, et al. Eosinophilic esophagitis: current concepts in diagnosis and management. Saudi J Gastroenterol 2024;30:210–227.
crossref pmid pmc
29. Menard-Katcher C, Swerdlow MP, Mehta P, Furuta GT, Fenton LZ. Contribution of esophagram to the evaluation of complicated pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 2015;61:541–546.
crossref pmid pmc
30. Nicodème F, Hirano I, Chen J, et al. Esophageal distensibility as a measure of disease severity in patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2013;11:1101–1107.e1.
crossref pmid pmc
31. Carlson DA, Hirano I, Gonsalves N, et al. A PhysioMechanical model of esophageal function in eosinophilic esophagitis. Gastroenterology 2023;165:552–563.e4.
crossref pmid pmc
32. Carlson DA, Shehata C, Gonsalves N, et al. Esophageal dysmotility is associated with disease severity in eosinophilic esophagitis. Clin Gastroenterol Hepatol 2022;20:1719–1728.e3.
crossref pmid pmc
33. Katzka DA, Ravi K, Geno DM, et al. Endoscopic mucosal impedance measurements correlate with eosinophilia and dilation of intercellular spaces in patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2015;13:1242–1248.e1.
crossref pmid
34. Reddy SB, Ketchem CJ, Dougherty MK, Eluri S, Dellon ES. Association between eosinophilic esophagitis and esophageal dysmotility: a systematic review and meta-analysis. Neurogastroenterol Motil 2023;35:e14475.
pmid
35. Friedlander JA, DeBoer EM, Soden JS, et al. Unsedated transnasal esophagoscopy for monitoring therapy in pediatric eosinophilic esophagitis. Gastrointest Endosc 2016;83:299–306; e1.
crossref pmid pmc
36. Katzka DA, Geno DM, Ravi A, et al. Accuracy, safety, and tolerability of tissue collection by Cytosponge vs endoscopy for evaluation of eosinophilic esophagitis. Clin Gastroenterol Hepatol 2015;13:77–83.e2.
crossref pmid
37. Furuta GT, Kagalwalla AF, Lee JJ, et al. The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis. Gut 2013;62:1395–1405.
crossref pmid pmc
38. Hirano I, Chan ES, Rank MA, et al. AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters clinical guidelines for the management of eosinophilic esophagitis. Gastroenterology 2020;158:1776–1786.
crossref pmid pmc
39. Rank MA, Sharaf RN, Furuta GT, et al. Technical review on the management of eosinophilic esophagitis: a report from the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters. Gastroenterology 2020;158:1789–1810.e15.
crossref pmid pmc
40. de Bortoli N, Visaggi P, Penagini R, et al. The 1st EoETALY consensus on the diagnosis and management of eosinophilic esophagitiscurrent treatment and monitoring. Dig Liver Dis 2024;56:1173–1184.
crossref pmid
41. Lucendo AJ, Arias Á, Molina-Infante J. Efficacy of proton pump inhibitor drugs for inducing clinical and histologic remission in patients with symptomatic esophageal eosinophilia: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2016;14:13–22.e1.
crossref pmid
42. Laserna-Mendieta EJ, Casabona S, Guagnozzi D, et al. Efficacy of proton pump inhibitor therapy for eosinophilic oesophagitis in 630 patients: results from the EoE connect registry. Aliment Pharmacol Ther 2020;52:798–807.
crossref pmid pdf
43. Gómez-Torrijos E, García-Rodríguez R, Castro-Jiménez A, Rodríguez-Sanchez J, Méndez Díaz Y, Molina-Infante J. The efficacy of stepdown therapy in adult patients with proton pump inhibitor-responsive oesophageal eosinophilia. Aliment Pharmacol Ther 2016;43:534–540.
crossref pmid
44. Sawas T, Dhalla S, Sayyar M, Pasricha PJ, Hernaez R. Systematic review with meta-analysis: pharmacological interventions for eosinophilic oesophagitis. Aliment Pharmacol Ther 2015;41:797–806.
crossref pmid
45. Alexander JA, Jung KW, Arora AS, et al. Swallowed fluticasone improves histologic but not symptomatic response of adults with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2012;10:742–749.e1.
crossref pmid
46. Dellon ES, Sheikh A, Speck O, et al. Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis. Gastroenterology 2012;143:321–324.e1.
crossref pmid pmc
47. Lucendo AJ, Miehlke S, Schlag C, et al. Efficacy of budesonide orodispersible tablets as induction therapy for eosinophilic esophagitis in a randomized placebo-controlled trial. Gastroenterology 2019;157:74–86.e15.
pmid
48. Straumann A, Lucendo AJ, Miehlke S, et al. Budesonide orodispersible tablets maintain remission in a randomized, placebo-controlled trial of patients with eosinophilic esophagitis. Gastroenterology 2020;159:1672–1685.e5.
pmid
49. Kliewer KL, Gonsalves N, Dellon ES, et al. One-food versus six-food elimination diet therapy for the treatment of eosinophilic oesophagitis: a multicentre, randomised, open-label trial. Lancet Gastroenterol Hepatol 2023;8:408–421.
crossref pmid pmc
50. Schoepfer AM, Henchoz S, Biedermann L, et al. Technical feasibility, clinical effectiveness, and safety of esophageal stricture dilation using a novel endoscopic attachment cap in adults with eosinophilic esophagitis. Gastrointest Endosc 2021;94:912–919.e2.
crossref pmid
51. Dellon ES, Rothenberg ME, Collins MH, et al. Dupilumab in adults and adolescents with eosinophilic esophagitis. N Engl J Med 2022;387:2317–2330.
crossref pmid
52. Chehade M, Dellon ES, Spergel JM, et al. Dupilumab for eosinophilic esophagitis in patients 1 to 11 years of age. N Engl J Med 2024;390:2239–2251.
crossref pmid
53. Aceves SS, Dellon ES, Greenhawt M, Hirano I, Liacouras CA, Spergel JM. Clinical guidance for the use of dupilumab in eosinophilic esophagitis: a yardstick. Ann Allergy Asthma Immunol 2023;130:371–378.
pmid
54. Dellon ES, Collins MH, Rothenberg ME, et al. Long-term efficacy and tolerability of RPC4046 in an open-label extension trial of patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2021;19:473–483.e17.
crossref pmid
55. Rothenberg ME, Dellon ES, Collins MH, et al. Eosinophil depletion with benralizumab for eosinophilic esophagitis. N Engl J Med 2024;390:2252–2263.
crossref
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