From esophagus to colon: A narrative review of eosinophilic gastrointestinal disorders

Abstract

Eosinophilic gastrointestinal disorders (EGID) are a heterogeneous group of chronic diseases characterized by excessive infiltration of eosinophils in the gastrointestinal tract in the absence of identifiable secondary causes. Primary EGID includes eosinophilic esophagitis, eosinophilic gastroenteritis, and eosinophilic colitis. The purpose of this review is to provide a concise overview of the current understanding and management of EGID. The published data were extracted by a comprehensive literature search in PubMed/MEDLINE with keywords related to EGID. The retrieved data were analyzed and synthesized into a narrative review emphasizing clinical features, evaluation, and treatment strategies. A brief outline of the etiopathogenesis of the disease was also derived from the published literature. EGID, especially esophagitis, has demonstrated an increasing global prevalence, more frequent in men and those with other atopic conditions. The etiology of EGID remains poorly understood, though allergic mechanisms are heavily implicated. Sensitization to foods or aeroallergens is common, yet only a minority experiences food-induced anaphylaxis, suggesting distinct non-IgE-mediated pathways in disease pathogenesis. Genetic factors and dysregulation in gene expression related to eosinophil recruitment, notably eotaxin-3, are implicated as well. The clinical manifestations vary according to the site of gastrointestinal tract involvement. The diagnosis relies on endoscopic biopsies to reveal the tissue eosinophilia. The treatment strategies include dietary modification or elimination diets, steroids and other anti-allergic medications, proton pump inhibitors, and monoclonal antibodies targeting eosinophils or key inflammatory cytokines. Therapeutic endoscopic procedures might benefit patients with strictures, particularly those involving esophagus.

Key Words: Eosinophilic; Gastrointestinal diseases; Esophagitis; Gastritis; Gastroenteritis; Colitis; Proton pump inhibitors

Core Tip: Eosinophilic gastrointestinal disorders encompass a spectrum of chronic, immune-mediated conditions characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes. Despite its increasing prevalence, significant gaps remain in awareness, diagnosis, and treatment of the disease. The diagnosis mandates demonstration of tissue eosinophilia, typically on gastrointestinal endoscopic biopsies, together with exclusion of secondary causes. The treatment involves dietary modifications, corticosteroids, proton pump inhibitors, and emerging biologics targeting key cytokine pathways. The lack of standardized guidelines emphasizes the need for multidisciplinary care and further research to refine diagnostic thresholds and optimize treatment strategies.

INTRODUCTION

Eosinophilic gastrointestinal disorders (EGID) are a group of chronic, immune-mediated diseases defined by excessive accumulation of eosinophils within the layers of the gastrointestinal tract, in the absence of identifiable secondary causes of eosinophilia. Primary EGID include eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic gastroenteritis (EoGE), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). By definition, these conditions are considered primary when other etiologies of eosinophilia, such as parasitic infections, drug hypersensitivity reactions, systemic allergic disorders, autoimmune diseases, or underlying malignancies, have been excluded[1]. The clinical manifestations of EGID depend upon the primary site of involvement and the depth of eosinophilic infiltration within the gastrointestinal tract (Figure 1). Diagnosis relies on the demonstration of tissue eosinophilia on endoscopic biopsies; the threshold varies across segments of the gastrointestinal tract (Figure 1). Management includes dietary elimination of potential triggers and pharmacotherapy, with corticosteroids as the mainstay. This article delves into the intricacies of EGID to provide the reader with an overview of its clinical and therapeutic aspects, a rare yet increasingly reported entity[2-5].

Figure 1 Summary of clinical manifestations and diagnostic criteria for eosinophilic gastrointestinal disorders. ¹Eosinophil per high power field.

SEARCH STRATEGY

A comprehensive PubMed/MEDLINE literature search was conducted to identify relevant studies/trials, reviews, meta-analyses, and guidelines on EGID. The following search string was utilized to identify the relevant articles (“Eosinophilic Esophagitis”[Mesh] OR “eosinophilic esophagitis”[tiab] OR EoE[tiab] OR “eosinophilic gastritis”[tiab] OR “Eosinophilic Gastritis”[Supplementary Concept] OR “eosinophilic gastroenteritis”[tiab] OR “Eosinophilic Gastroenteritis”[Mesh] OR “eosinophilic enteritis”[tiab] OR “eosinophilic colitis”[tiab] OR “Eosinophilic Gastrointestinal Diseases”[tiab] OR “eosinophilic gastrointestinal disorder*”[tiab] OR EGID[tiab] OR EGIDs[tiab]) AND (epidemiolog*[tiab] OR pathogenes*[tiab] OR etiolog*[tiab] OR mechanis*[tiab] OR diagnos*[tiab] OR biopsy[tiab] OR histolog*[tiab] OR endoscop*[tiab] OR “eosinophil* per high power field”[tiab] OR treatment[tiab] OR therap*[tiab] OR management[tiab]) AND (english[lang]) AND (“2000/01/01”[Date-Publication]: “2025/10/31”[Date-Publication]). The following article filters were applied to narrow the search: Case reports, clinical study, clinical trial, controlled clinical trial, evaluation study, guideline, meta-analysis, multicenter study, observational study, randomized controlled trial, review. Reference lists of key articles and recent reviews were manually screened for additional relevant publications. The final search identified 2327 manuscripts. The data was screened by the authors and extracted on study design, population, diagnostic criteria, clinical presentation, histopathology, and management strategies. The narrative review was structured by anatomical site (esophagus, stomach, small intestine, colon) and by key clinical domains (epidemiology, etiopathogenesis, clinical features, diagnosis, and management). Given the objective of this manuscript, to provide a broad narrative overview rather than a quantitative synthesis, and due to substantial heterogeneity in study designs, populations, and outcome measures across the available literature, a systematic review was not undertaken. As a narrative review, this article may be subject to selection bias.

EoE

Epidemiology

EoE is defined by symptoms of esophageal dysfunction and eosinophil-predominant inflammation on biopsy, after exclusion of other causes of esophageal eosinophilia[6]. A 2023 global meta-analysis of 40 studies estimated a pooled incidence of 5 per 100000 per year and a prevalence of 40 per 100000, with prevalence rising from 8 per 100000 in 1976-2001 to 74 per 100000 in 2017-2022[7]. In the United States, a 2025 study estimated a national prevalence of 142.5 per 100000 (about 1 in 700), corresponding to roughly 472000 people living with EoE, with higher rates in men and among those aged 40 to 44 years[8]. Across Europe, a 2024 meta-analysis estimated a pooled prevalence of 32 per 100000 and showed rising incidence in both adults and children[9]. A 2025 Asia-focused meta-analysis estimated a pooled prevalence of about 34 per 100000 and showed a steady increase over the past decade[10]. In studies from the United States, 89% are European Americans, while African Americans and Asians account for only 10%. The reasons behind the stark ethnic and racial disparities are largely unclear; explanations include genetic factors, differences in clinical awareness and diagnostic practices[11]. Furthermore, prevalence is consistently higher in men and in individuals with atopic disease, with rates greater in high-income settings[7]. The incidence of EoE is rising, partly because of greater awareness and more frequent esophageal biopsies during endoscopy. Even after accounting for these factors, studies show an actual increase in incidence, similar to trends seen in other atopic diseases[12].

Etiopathogenesis

The underlying cause of EoE remains incompletely understood, although allergic mechanisms are strongly implicated. Most patients demonstrate sensitization to foods or aeroallergens, as shown by skin prick testing or radioallergosorbent test (RAST), yet only a small subset has a history of food-induced anaphylaxis. This suggests that EoE operates through pathways distinct from classical IgE mediated mast cell or basophil activation[13]. Evidence indicates that EoE is driven by a Th2 predominant immune response, with increased expression of eosinophil-activating cytokines such as interleukin (IL)-4, IL-5, and IL-13, as well as an accumulation of mast cells within the esophageal tissue. These findings highlight the interplay between allergic sensitization, Th2 cytokines, and eosinophilic inflammation across the respiratory tract and esophagus. Clinically, some patients report seasonal variation in symptoms, paralleling fluctuations in esophageal eosinophil counts[14,15].

Molecular studies using whole-genome microarray analysis have identified dysregulation of about 1% of the genome in EoE. Among these, eotaxin-3 is the most significantly upregulated gene, showing a 50-100-fold increase compared with controls. This gene expression pattern is consistent across allergic and nonallergic patients, suggesting a conserved effector pathway regardless of the initiating trigger. IL-13 appears to be a central mediator by promoting eotaxin-3 production in esophageal epithelial cells, which in turn recruits C-chemokine receptor-3 positive eosinophils. Unlike other eotaxins, eotaxin-3 is uniquely overexpressed in EoE, underscoring its specificity in disease pathogenesis. Mouse models reinforce this pathway: Deletion of STAT6 or IL-13 impairs allergen-induced EoE, and blockade of IL-5 attenuates eosinophilic infiltration. Collectively, these findings place IL-13-driven eotaxin-3 production and Th2 cytokine signaling at the center of EoE pathogenesis[16].

Approximately 10% of affected children have parents with esophageal strictures, and about 8% have biopsy-confirmed EoE. In large pediatric cohorts, multiple sibling cases have been documented, as have reports of affected adult siblings. The sibling recurrence risk ratio (λS) for EoE is estimated at about 80, far higher than that for common allergic diseases like asthma (λS approximately 2). This strikingly elevated risk underscores the significant contribution of genetic factors. One important candidate gene is eotaxin-3. A specific single-nucleotide polymorphism (SNP) in the 3′-untranslated region of eotaxin-3 has been associated with EoE, potentially influencing mRNA stability and cytokine responsiveness. This SNP resides in strong linkage disequilibrium with nearby variants, forming a haplotype block likely contributing to disease susceptibility[17].

Histologic studies in patients with EoE show deposition of major basic protein (MBP) in the esophagus, consistent with eosinophil degranulation. Eosinophil granule proteins, including Charcot-Leyden crystal protein and eosinophil-derived neurotoxin, exhibit cytotoxicity and may serve as noninvasive biomarkers. Indeed, correlations have been observed between EoE activity and blood levels of eosinophil-derived proteins and eotaxin-3. Besides eosinophils, lymphocytes, and mast cells also play roles in EoE. Both are increased in esophageal tissue, with upregulation of their signature genes. IL-5, produced by Th2 cells, appears central. Experimental ablation of IL-5 or treatment with anti-IL-5 antibodies significantly reduces allergen and IL-13-induced esophageal eosinophilia[18].

Clinical features

The clinical presentation of EoE varies by age group. Infants and young children often present with non-specific symptoms such as feeding difficulty, vomiting, abdominal or retrosternal pain, and poor growth. Adolescents and adults typically have solid food dysphagia with intermittent food bolus obstruction or food impaction, whereas heartburn, regurgitation, dyspepsia, and chest discomfort are relatively less specific. Roughly 50% of patients seen in the emergency department for an esophageal food impaction requiring endoscopic removal are ultimately diagnosed with EoE[19,20].

In patients with EoE, prolonged uncontrolled inflammation is associated with fibrostenotic remodeling, resulting in fixed esophageal strictures. A cohort study of 200 patients with EoE from Switzerland reported that, among patients with symptoms lasting more than 20 years at the time of diagnosis, esophageal strictures and fibrotic endoscopic features were identifiable in 70.8% and 87.5%, respectively. For patients with symptom duration of less than two years at the time of diagnosis, the corresponding proportions were 17.2% and 46.5%, respectively. It was estimated that for each additional year of diagnostic delay, the odds of stricture increased by 8%[21]. The strictures lead to dysphagia and recurrent food bolus impactions[21]. If not promptly disimpacted, these episodes can lead to esophageal perforation or, in exceptional circumstances, intramural esophageal dissection[22-26]. Patients with EoE often adapt their eating habits by chewing more carefully, consuming soft foods, and frequently drinking water during meals[22].

Diagnosis

The diagnosis of EoE requires a constellation of (1) Symptoms of esophageal dysfunction; (2) > 15 eosinophils per high power field (hpf); and (3) Exclusion of alternate cases of esophageal eosinophilia. The preferred diagnostic technique for suspected EoE is upper gastrointestinal endoscopy with biopsies. Endoscopic findings include trachealization with concentric rings, longitudinal furrows, white exudates, mucosal edema, and fixed stricture (Figure 2)[22]; however, the esophagus can appear normal in a minority of cases[24,25]. As the disease can be patchy, sampling for histology should be generous: At least six specimens from multiple sites in the proximal and distal esophagus, plus a targeted biopsy of the abnormal mucosa, if present[25]. The diagnostic threshold is at least 15 eosinophils per hpf in the most affected area of the esophageal biopsy (Figure 3). This cutoff reportedly has 100% sensitivity and 96% specificity for diagnosing EoE. Other microscopic findings include eosinophilic microabscesses, epithelial hyperplasia, spongiosis, and eosinophil degranulation. The EoE Histology Scoring System, helps in assessing the diseases extent and severity, as well for monitoring the disease activity over time. The scoring system takes into account the esophageal eosinophil count, eosinophilic abscess, eosinophil surface layering, basal zone hyperplasia, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis[26,27]. Tissue staining with eosinophil peroxidase can be used in patients with typical features, but eosinophil counts below the cut-off[28].

Figure 2 Endoscopic appearance in eosinophilic esophagitis[22]. A: White exudates; B: Concentric rings of the esophageal wall, properly termed trachealization; C: Loss of vascular markings reflecting edema of the esophageal mucosa; D: Longitudinal furrows; E: Fixed stricture; F: Combination of multiple inflammatory signs such as furrows, edema, and exudates. Citation: Straumann A, Schoepfer A. Update on basic and clinical aspects of eosinophilic oesophagitis. Gut 2014; 63: 1355-1363. Copyright© The Authors 2026. Published by BMJ Publishing Group. The authors have obtained the permission (Supplementary material).

Figure 3 Esophageal epithelium in long-standing eosinophilic esophagitis. Microphotograph shows a marked increase of fibrotic tissue in the subepithelial layer (white arrow)[22]. Citation: Straumann A, Schoepfer A. Update on basic and clinical aspects of eosinophilic oesophagitis. Gut 2014; 63: 1355-1363. Copyright© The Authors 2026. Published by BMJ Publishing Group. The authors have obtained the permission (Supplementary material).

The esophageal string test and the Cytosponge are two string-based minimally invasive tests that allow cell sampling from the esophagus. The retrieved cells are assessed for eosinophils to support the diagnosis of EoE[29]. Katzka et al[30] compared conventional histology with Cytosponge test for diagnosis of EoE. Cytosponge was shown to have 83% sensitivity and 57% sensitivity for diagnosing active EoE; it correlated well with histology[30]. Endoscopic ultrasound imaging has revealed thickening of esophageal layers in patients with EoE; however, the findings are non-specific[28]. The endoscopic functional luminal imaging probe (EndoFLIP) is a novel imaging modality that can identify the altered esophageal wall compliance and aid in diagnosis. The Eosinophilic Esophagitis Diagnostic Panel is a molecular model that detects expression of 96 genes altered in patients with EoE. The molecular panel has very high sensitivity and specificity for diagnosing EoE; it is especially used in patients in whom conventional tests are indeterminate[28].

Multiple serum biomarkers have been evaluated for the diagnostic role in patients with EoE. Peripheral eosinophilia and elevated serum IgE have been demonstrated in patients with EoE, but often fail to correlate with tissue eosinophilia[29]. Serological assays for periostin, eosinophil cationic protein, eosinophil-derived neurotoxin, and MBP have been evaluated to distinguish patients with EoE from healthy subjects; however, most have met with limited benefits[31]. Several other conditions can result in esophageal eosinophilia (Table 1) and should be excluded before confirming the diagnosis of EoE. Gastroesophageal reflux disease (GERD) shares clinical and histological features with EoE and poses a diagnostic challenge. Table 2 summarizes the key differences between EoE and GERD.

Table 1 Differential diagnoses of esophageal eosinophilia.

Diagnoses of esophageal eosinophilia
Gastroesophageal reflux disease
Achalasia
Crohn's disease
Parasitic infection
Drug hypersensitivity
Connective tissue diseases (e.g., scleroderma)
Celiac disease
Hypereosinophilic syndrome
Proton pump inhibitor-responsive esophageal eosinophilia

Table 2 Clinico-pathological comparison of eosinophilic esophagitis and gastroesophageal reflux disease.

	Eosinophilic esophagitis	Gastroesophageal reflux disease
Pathophysiology	Chronic immune mediated (Th2) disease of the esophagus	Acid-mediated mucosal injury from reflux of gastric contents
Age/gender	Children and young adults. Male predilection	All age groups, more common in adults. No sex predilection
Associations	Atopy, allergies	Obesity, pregnancy, hiatal hernia
Clinical symptoms	Dysphagia, food impaction	Heartburn, regurgitation
Endoscopic findings	Rings, linear furrows. White exudates, strictures	Erosions, erythema, ulceration, hiatal hernia
Distribution	Patchy; proximal, distal esophagus	Predominantly distal esophagus
Histologic criteria	≥ 15 eosinophils/hpf	< 15 eosinophils/hpf
Esophageal pH	Usually normal	Acid exposure
Treatment	PPI, swallowed corticosteroids, diet	PPI, H2RB, lifestyle modifications
Response to PPI	Variable: Partial or absent	Robust response
Response to dietary intervention	Good	Minimal
Complications	Fibrosis, strictures. Recurrent food impaction	Barrett’s esophagus. Adenocarcinoma

hpf: High power field; PPI: Proton pump inhibitors; H2RB: Histamine-2 receptor blockers.

Treatment

The therapeutic approach to EoE includes dietary, pharmacological, and endoscopic strategies[32]. While no agents are currently approved by the United States Food and Drug Administration (FDA) specifically for EoE, several options have shown benefit in clinical practice. Management often involves shared decision-making, weighing the advantages and limitations of each modality.

Diet

Dietary modification can induce histologic remission in patients, particularly children, and is a common first-line intervention. Three primary strategies are used: An elemental diet, empiric food elimination, and allergy test-directed elimination of food.

The elemental diet replaces all food intake with an amino acid-based liquid formula containing carbohydrates, fats, vitamins, and minerals. A meta-analysis of 43 studies involving 2825 patients reported a histologic remission rate of 94.5% with the elemental diet[33]. Despite its high efficacy, this approach is limited by high cost, poor palatability, and the social burden of complete food avoidance. When foods are reintroduced, it is typically done gradually under allergist supervision to minimize the risk of developing new IgE-mediated allergies[34].

Empiric elimination involves avoiding the six most common food triggers in EoE, namely milk, wheat, eggs, soy, peanuts, and fish or shellfish[35]. The six-food elimination diet has achieved histologic remission in 63.9% of patients in a recent meta-analysis of 43 studies[33]. Less restrictive variations, such as a four-food elimination diet (milk, wheat, eggs, and legumes) or a two-food elimination diet (milk and cereal), have been evaluated, showing remission rates of 56.9% and 42.1%, respectively[33]. In responders, food materials are reintroduced sequentially with interval endoscopic assessment to confirm sustained remission[35,36]. The choice between step-down and step-up elimination strategies should be made collaboratively with the patient, balancing efficacy with feasibility.

An alternate dietary approach is an allergy test-targeted elimination of food. This approach uses skin prick tests, patch testing, or serum IgE assays to identify potential triggers for removal. Due to the non-IgE-mediated nature of EoE, the effectiveness of this approach is limited, with recent evidence indicating histologic remission rates of approximately 40%, which are lower than those achieved with empiric or elemental diets[33].

Pharmacotherapy

The medical management of EoE primarily involves proton pump inhibitors (PPI) and swallowed topical corticosteroids, with combination regimens reserved for refractory cases.

Initially used to distinguish EoE from PPI-responsive esophageal eosinophilia, PPI are now recognized as a therapeutic option[6]. In addition to gastric acid suppression, PPI can exert anti-inflammatory effects through cytokine modulation, inhibition of immune cell function, and antioxidant activity[37]. Meta-analyses report histologic remission rates of approximately 40%-42%, with symptom improvement in around 60% of patients[38]. PPI are generally well tolerated, cost-effective, and convenient, making them a reasonable first-line therapy. Potential long-term risks include enteric infections and micronutrient deficiencies, although current evidence for causality is limited and effect sizes are small[39].

Swallowed topical corticosteroids, most commonly fluticasone (administered via metered-dose inhaler and swallowed) and budesonide (oral viscous suspension or oral dispersible tablet), are considered the mainstay of pharmacologic therapy for EoE[40,41]. Randomized controlled trials have shown histologic remission rates exceeding 90% with oral budesonide formulations[40]. Typical adult dosing regimens include fluticasone 880 µg twice daily or budesonide 1-2 mg twice daily. Observational studies of standard therapies have shown that approximately 57% of patients experience symptomatic recurrence within one year after cessation of topical steroid therapy, with histologic relapse occurring in up to 78% over the same period[42]. Adverse effects are usually mild; esophageal candidiasis occurs in approximately 12%-20% of cases and is often asymptomatic, while adrenal suppression is rare[40,41].

For patients with persistent disease despite monotherapy, combination regimens incorporating dietary elimination, PPI, and topical corticosteroids can be considered. Small observational cohorts suggest symptom control rates exceeding 80% with combination strategies, although the relative contribution of each treatment component is often unclear[43]. Additionally, combination therapy increases cost and complexity, potentially affecting adherence[43].

Monoclonal antibodies targeting eosinophils or key inflammatory cytokines such as IL-4 and IL-13 are in advanced clinical stages and may benefit patients with refractory disease or concomitant atopic disorders. Agents like dupilumab, cendakimab and lirentelimab have shown promising histological and symptomatic improvements in randomized trials, current guidelines recommend restricting their use to clinical trial settings until further safety and efficacy data are available[44].

Maintenance therapy, either dietary or pharmacologic, is generally recommended for individuals with a history of strictures, severe narrowing, or rapid symptom recurrence. Long-term use of budesonide orodispersible tablets has resulted in sustained remission in over 70% of patients[45].

Endoscopic treatment

Endoscopic esophageal dilation is indicated for patients with fibrostenotic changes, high-grade strictures, or persistent dysphagia despite medical therapy. It widens the esophageal lumen and provides symptomatic relief in about 95% of cases, with a median duration of benefit of 12 months[46]. In a meta-analysis of 37 studies involving 2034 dilations in 977 patients with EoE, post-procedural chest pain occurred in 23% of cases, making it the most frequent adverse event[46]. Serious complications, such as esophageal perforation, remain very rare: < 0.05%[47]. As endoscopic esophageal dilation does not address the underlying eosinophilic inflammation, it is ideally performed in conjunction with anti-inflammatory therapy to achieve both structural and histologic disease control[48].

EoGE

Epidemiology

EoGE encompasses a spectrum of rare, eosinophilic inflammatory disorders involving the stomach and intestines. First described in 1937, this rare disorder continues to be diagnosed sporadically, with an estimated prevalence of 8-28 per 100000 in the United States[49]. It is more frequent in the pediatric population; affected adults are typically in their third to fifth decade of life. A slight male predominance has been reported in published literature[50].

Etiopathogenesis

The precise etiopathogenesis of the disorder remains to be elucidated, but it is primarily attributed to sensitivity reactions. IgE-mediated allergic responses to a myriad of food materials have been implicated in the pathogenesis, with cow’s milk, wheat, and eggs being the frequent offenders[51]. Patients often report a personal or family history of immunoallergic disorders in 45% to 63% and 64%, respectively, further emphasizing the role of IgE in the pathogenesis[49].

Alternatively, a Th2-mediated response with IL-5 release could trigger eosinophil chemotaxis. Once in the tissue, eosinophils can release IL-5, IL-3, and leukotrienes, which promote eosinophil recruitment[49,50]. Gastrointestinal tissue eosinophilia could also develop secondary to parasitic infections, inflammatory bowel disease (IBD), malignancies, autoimmune diseases, and drug allergies. Familial clustering of cases also points to possible underlying genetic predisposition[49].

Clinical features

The clinical manifestations of EoGE are heterogeneous and depend on the location, depth, and extent of eosinophilic infiltration. Klein et al[3] classified EoGE into mucosal, muscular, and serosal diseases based on the predominant site of inflammatory infiltration, the mucosal variant being the most common. Mucosal disease: Diarrhea, emesis, malabsorption, weight loss[49]. Serosal disease: The least common variant, presents with ascites[49]. Muscular disease: Manifests as colics and intestinal obstruction[49].

Concomitant involvement of multiple layers is not infrequent, raising the possibility of the disease being a progressive pathology extending centrifugally from the mucosa. Uncommon presentations include pyloric stenosis, appendicitis, bowel perforation, and obstructive pancreatitis[50]. Predominant involvement of the gastroesophageal junction, or concurrent EoE, may present with dysphagia.

Diagnosis

The diagnosis of EoGE requires: (1) Presence of gastrointestinal symptoms; (2) Demonstration of pathologic tissue eosinophilia; and (3) Exclusion of secondary causes of eosinophilia. No single laboratory test is diagnostic. Peripheral eosinophilia is observed in up to 70% of patients, while elevated IgE levels are documented in up to two-thirds of patients[49]. Other non-specific laboratory abnormalities include anemia, micronutrient deficiencies, and hypoalbuminemia. Ascitic fluid analysis in serosal disease can demonstrate eosinophilic cellularity. Secondary causes must be excluded with stool/serum assays for parasitic infections and evaluation for IBD or neoplasia[52]. Allergy testing shows positive responses in up to 50% of patients, but results are non-specific and not diagnostic[49].

Endoscopy with biopsy is the preferred modality of tissue sampling. Gross findings are often non-specific: Mucosal erythema, erosions, ulcers, and polyps. However, in large-scale studies, the most frequent finding is a normal mucosa[53,54]. Because involvement may be patchy, multiple-site biopsies are necessary. Since endoscopic biopsies usually include only mucosa, muscular or serosal disease may be missed. In cases with high suspicion, repeat or deeper biopsies, endoscopic mucosal resection, or endoscopic ultrasound-guided biopsy may be required[49,55]. The recommended thresholds for tissue eosinophilia for diagnosis of EoGE are: Stomach: ≥ 30 eosinophils/hpf[52,53]; Duodenum: ≥ 52 eosinophils/hpf[52,53]; Ileum: ≥ 56 eosinophils/hpf[52,53].

Cross-sectional abdominal imaging can identify bowel wall thickening and ascites, while also ruling out alternative causes. Technetium-99m hexamethylpropylene amine oxime-labeled white blood cells scintigraphy may be used to demonstrate areas of eosinophilic infiltration[52].

Treatment

There are no widely accepted consensus guidelines for EoGE. Current therapeutic strategies are empirical and adapted from those used in EoE or other allergic disorders. Options include dietary therapy, PPI, and immunoallergic medications.

Diet

Dietary modifications have been evaluated in patients with EoGE to exclude allergens that could trigger an eosinophilic response.

Elimination diets: The 6-food elimination diet, milk, eggs, wheat, nuts, seafood, and soy, is most common, while the 7-food elimination diet additionally excludes red meat[56]. Studies report variable response, more evident in pediatric patients and those with mucosal EoGE[56-58]. A prospective study by Gonsalves et al[57] reported improvement in symptoms, histology, and peripheral eosinophilia in 57.1% of adults with EoG after a 6-food elimination for 6 weeks.

Elemental diets: Unlike in EoE, the data on the role of elemental diet in EoGE are limited. In a prospective trial by Gonsalves et al[59], an elemental diet for six consecutive weeks resulted in clinical, endoscopic, and histological responses in patients with EoGE. However, the patients relapsed with the reintroduction of a regular diet[59].

Pharmacotherapy

PPIs and various molecules targeting immunoallergic pathways have been evaluated with varying degrees of success in patients with EoGE.

PPI: Lansoprazole or pantoprazole has been reported to reduce eosinophilia, possibly via acid suppression and modulation of Th2 cytokines[60,61]. The data, however, are sparse, and the postulated mechanisms remain unproven, limiting recommendations regarding the use of PPI.

Corticosteroids are often considered first-line treatment. Retrospective studies have demonstrated an excellent response to prednisone, either alone or in combination with other therapies, with the latter yielding superior results[5,62]. The recommended induction dose of prednisone is 0.5-1 mg/kg, followed by a gradual taper over 6 to 8 weeks. Steroid dependence is reported in as high as 20% of responders[49]. Budesonide is a safer alternative with fewer systemic effects, owing to high hepatic first-pass metabolism[63-65]. The recommended induction dose is 9 mg/day, which could be later tapered and continued for a longer duration with less toxicity[49].

Montelukast has shown benefit, especially as a steroid-sparing agent. Trials in pediatric and adult patients show symptomatic relief, but relapse is common after discontinuation[58,66,67]. Cromolyn sodium, a mast cell stabilizer, has shown benefits in case reports, but lacks large-scale studies[68-70]. In a small case series, Ketotifen, an antihistaminic agent, provided symptomatic relief and improvement in serum IgE levels and tissue eosinophilia[71].

Monoclonal antibodies targeting IgE (omalizumab), IL-5 (mepolizumab), and tumor necrosis factor-alpha (infliximab, adalimumab) have been evaluated in a handful of cases with variable responses[49]. Interferon-α, intravenous immunoglobulin, and suplatast tosilate (Th2 response inhibitor) have shown benefit in refractory cases[49,72-74].

EoC

Epidemiology

EoC is a rare inflammatory disease of the colon characterized by primary eosinophilic infiltration of the colonic wall[58,75]. The true prevalence is difficult to determine due to the absence of standardized diagnostic criteria. A United States population-based study estimated the prevalence at 2.1 per 100000 individuals, higher in adults (2.3/100000) than children (1.6/100000), with a slight female and Caucasian predominance[76]. Some reports suggest a bimodal age distribution, peaking in neonates and adults[5,77].

Etiopathogenesis

The development of EoC is likely multifactorial, involving genetic predisposition, microbial imbalance, and environmental factors. In infants, EoC appears to be IgE-mediated and associated with food proteins, whereas in adults, it is more often driven by Th2-mediated immune responses. EoC is more common in urban and suburban populations and is associated with allergic diseases such as asthma, rhinitis, eczema, dermatitis, food allergies, and urticaria[5]. Also, they are linked to autoimmune diseases such as IBD, celiac disease, systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis[78-83].

Eosinophils are typically abundant in the intestinal lamina propria and play roles in defense against pathogens, regulation of the microbiome, and tissue maintenance[84,85]. Their activation is mediated by cytokines secreted by Th2 lymphocytes and mast cells. Once activated, eosinophils release cytotoxic proteins, leukotrienes, and cytokines that influence immune function, including dendritic cell activation and IgA class switching[86].

Clinical features

The clinical manifestations of EoC are heterogeneous. Infants typically present acutely with bloody diarrhea, often food-related, resolving after allergen elimination. Adults usually present more insidiously with abdominal pain, watery diarrhea, weight loss, and sometimes concomitant upper gastrointestinal symptoms. Atopic conditions are common comorbidities. The severity of the disease depends on the depth of eosinophilic infiltration: Mucosal (Type 1): Most common; diarrhea, bleeding, protein-losing enteropathy; chronic continuous course; transmural (Type 2): Involves full wall thickness; can cause obstruction, strictures, volvulus, or perforation; relapsing-remitting course; subserosal (Type 3): Rarest; presents with eosinophilic ascites; usually a single, self-limited episode[87,88].

Diagnosis

Endoscopic findings in EoC are often nonspecific, as the colonic mucosa may appear normal in many cases. When present, abnormalities can include loss of the vascular pattern, erythema, mucosal granularity, or superficial ulcerations, though these changes are typically subtle[79,88]. The diagnosis relies on histological evaluation from multiple colonic biopsies. The absence of standardized criteria and the patchy distribution of eosinophils within the mucosa often make the diagnosis challenging[89]. Eosinophils are most frequently identified in the lamina propria but may also extend through the muscularis mucosa into the submucosa. In some cases, infiltration can involve the muscularis propria, leading to eosinophilic crypt abscesses or lymphoid nodular hyperplasia[90,91]. Collins et al[90] recommended obtaining multiple biopsies from different colonic sites and submitting them separately to pathology with precise labeling of the site of origin. Colonic eosinophilia is defined as having an eosinophil count greater than the upper limit of normal in at least one colonic site, > 100 eosinophils/hpf in the ascending colon, > 84 eosinophils/hpf in the transverse and descending colon, > 64 eosinophils/hpf in the rectosigmoid colon[90].

Adjunctive diagnostic tools may provide additional support. Peripheral eosinophilia does not consistently correlate with tissue eosinophilia[88]. Allergy testing, including patch, prick, or RAST, can help identify IgE-mediated forms linked to food or inhalant allergens[87]. In children, computed tomography frequently demonstrates colonic, often cecal, and ileal wall thickening, as well as pneumatosis involving the rectum[91]. In adults, imaging may reveal bowel wall thickening, strictures, polypoid or ulcerative lesions, a stiff ileocecal valve, and mucosal fold irregularities. Characteristic radiographic patterns include the “halo sign”, reflecting submucosal edema, and, in mucosal EoC, the “araneid limb-like sign”, which is also seen in EoN[92]. Colonic eosinophilia may be secondary to other diseases (Table 3) and must be excluded before diagnosing primary EoC; thus, it remains a diagnosis of exclusion.

Table 3 Differential diagnoses of colonic eosinophilia.

Parasitic infections	Strongyloides stercoralis, Enterobius vermicularis, Trichuris trichiura
Drugs	Clozapine, carbamazepine, rifampicin, gold, NSAIDs, tacrolimus
Transplant-related	Prolonged immunosuppression (e.g., tacrolimus in liver transplant recipients)
Systemic disorders	Hypereosinophilic syndrome, Churg-Strauss, autoimmune diseases
IBD overlap	Eosinophilic infiltration may mimic or precede ulcerative colitis
Others	Radiation colitis, Tolosa-hunt syndrome

IBD: Inflammatory bowel diseases; NSAIDs: Nonsteroidal anti-inflammatory drugs.

Treatment

Dietary modification and pharmacotherapy are the most frequently adopted treatment strategies.

Diet

In children, dietary elimination of trigger foods is often sufficient to control symptoms and inflammation. In adults, however, the response to dietary modification has been inconsistent, and usually pharmacological therapy is necessary.

Pharmacotherapy

Corticosteroids are considered the first-line therapy and act by suppressing eosinophil-stimulating cytokines[93]. Prednisone typically induces remission within two weeks, but relapse may occur during tapering, leading to steroid-dependent disease that requires maintaining the lowest effective dose. Budesonide, particularly in controlled ileal-release form, is an alternative for maintenance due to its strong local effect and lower risk of systemic side effects[63].

Immunomodulators like azathioprine or 6-mercaptopurine are second-line options for severe, refractory, or steroid-dependent cases[94]. Leukotriene receptor antagonist, montelukast, has shown benefit in maintaining remission in steroid-dependent EoC.

Surgical intervention is reserved for complications such as obstruction or perforation, particularly in muscular-type EoC. A case report described remission following fecal microbiota transplantation combined with steroids in a refractory patient, though no formal recommendations currently exist[95].

NOVEL THERAPIES IN EGID

Multiple therapeutic molecules are being evaluated in the management of EGID, especially EoE. Most of these medications are currently used off-label, with varying degrees of evidence and success. As of October 2025, only two molecules have received FDA approval for treatment of EoE: Dupilumab and budesonide oral suspension (Eohilia^®). Interestingly, there are no FDA-approved molecules for the treatment of other EGID to date.

Dupilumab was the first agent to be approved for the treatment of EoE in May 2022. Dupilumab is a monoclonal antibody that binds to IL-4 receptor alpha, thereby blocking IL-4 and IL-13 signaling, a key step in the Th2 inflammatory pathway[96]. The LIBERTY EoE TREET study, a randomized, multicenter, double-blind study, demonstrated improvements in the histological, symptomatic, and endoscopic domains of EoE at 24 weeks of dupilumab therapy. The favorable response was maintained or continued to improve to 52 weeks[97]. The recommended dose is 300 mg every week, administered as a subcutaneous injection, for adults weighing ≥ 40 kg. In 2024, the approval for the agent was extended to use in children older than 1 year, following the EoE KIDS Trial[98].

The FDA approved Budesonide oral suspension (Eohilia^®) in February 2025 for the treatment of EoE. It is approved for use in patients aged 11 years or above. Hirano et al[99] demonstrated histologic, symptomatic, and endoscopic improvements in patients aged 11 to 55 years. The recommended dose of budesonide oral suspension in EoE is 2 mg, twice daily for 12 weeks. The other molecules being evaluated in the management of EGID are summarized in Table 4.

Table 4 The emerging molecules in management of eosinophilic gastrointestinal disorders.

Molecule	Mechanism	Development phase
Cendakimab	Anti IL-13. Reduce eotaxin-3 mediated eosinophil recruitment	Phase 2
Mepolizumab	Anti IL-5. Reduces eosinophil survival/activation	Phase 2
Benralizumab	Anti IL-5Rα. Induces near-complete eosinophil depletion	Phase 3
Tezepelumab	Anti-TSLP. Blocks epithelial “alarmin” TSLP upstream of Th2 cascade	Phase 3
Lirentelimab	Anti-Siglec-8. Depletes eosinophils and inhibits mast cells	Phase 2/3

IL: Interleukin; TSLP: Thymic stromal lymphopoietin; Th2: T helper type 2.

CONCLUSION

EGID are increasingly recognized as immune-mediated diseases. Diagnosis remains challenging due to overlapping clinical features, patchy involvement, and the necessity to exclude secondary etiologies. Dietary interventions, PPI, and corticosteroids form the mainstay of therapy, though most scientific data is based on EoE and subsequently extrapolated to the spectrum of disease. Further well-designed clinical trials and consensus guidelines are needed to refine diagnostic thresholds, establish standardized treatment algorithms, and explore novel therapeutic targets. Emerging biologics targeting key cytokine pathways hold promise, particularly for refractory disease, though long-term efficacy and safety remain under investigation.