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].

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.

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.

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 (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 (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 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].

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 (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 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].

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, 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.

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.