EoE arises from genetic and environmental factors. Genetic risk (~20%) involves TSLP and CAPN14 gene variants driving Th2 inflammation and epithelial dysfunction. Environmental triggers (pet exposure, C-section, low H. pylori) support the hygiene hypothesis. Rising EoE prevalence in developed nations has been linked to sanitation, diet, and microbial exposure shifts. Seasonal allergens (e.g., Aspergillus) suggest airborne antigen involvement. EoE integrates Th2 cytokines (IL-5, IL-13), drivers of fibrogenesis (TGF-β, periostin), and epithelial barrier defects. Eosinophil degranulation releases cytotoxic proteins, causing tissue damage and motility issues.

EoE is diagnosed based on clinical semiology, endoscopic findings, and histological findings. Dysphagia is the most common symptom, though patients may describe it variably [12, 20]. Many unconsciously adapt by altering eating habits, leading to compensated dysphagia, which may only be revealed through detailed history-taking [21]. Other frequent symptoms include heartburn, chest pain, and epigastric discomfort [17, 22].

Physical examination is generally not useful for diagnosing EoE. However, since nearly 50% of patients have coexisting allergic conditions, findings indicative of bronchial asthma, allergic rhinitis, or atopic dermatitis may be present [12].

Laboratory testing has limited diagnostic value for EoE. Peripheral eosinophilia occurs in ~30% of patients but is typically mild and counts pertain to just above the 500 eosinophils/μL threshold [12, 18]. Serum IgE is often elevated, but no specific allergen IgE has been consistently identified [17]. Attempts to establish reliable blood biomarkers, such as eotaxin-3 and IL-5, have been unsuccessful due to poor correlation with disease severity [23]. The esophageal string test, which collects esophageal secretions, is being explored as a non-invasive diagnostic tool [24]. Emerging non-invasive diagnostic methods, such as Cytosponge for esophageal cell collection and Raman spectroscopy-based eosinophil peroxidase detection, are under investigation [25, 26].

Endoscopic findings in EoE include concentric rings (trachealization), linear furrows, white plaques, and strictures, present in 70% of cases, but they are not pathognomonic [12, 20]. Additional features, such as fragile “crepe paper” mucosa and tissue firmness (tug sign), may aid diagnosis [22]. However, 30% of patients have a normal-appearing esophagus, making multiple biopsies essential [17]. The EoE Endoscopic Reference Score (EREFS) standardizes evaluation, thereby improving diagnostic consistency [27]. Given the patchy nature of inflammation, at least 5–6 biopsies from different esophageal sites are recommended [28]. Strictures can be missed on endoscopy, highlighting its diagnostic limitations [29].

EoE is confirmed by identifying ≥ 15 eosinophils per HPF in esophageal mucosal biopsies (Figure 1). Due to patchy distribution, at least five samples from different regions are recommended for accurate diagnosis [21]. Eosinophil infiltration is typically denser in distal esophageal regions with the presence of white plaques or furrows [12, 20]. Additional histological features include eosinophil degranulation, eosinophilic microabscess, basal cell hyperplasia, spongiosis, dilated intercellular spaces, and papillary elongation [30, 31]. Eosinophil counts vary widely due to differences in biopsy sampling, staining methods, and HPF definitions. Inter-observer variability among pathologists further complicates borderline cases. Endoscopic practices also differ, with inconsistent biopsy numbers and sites affecting diagnostic yield. Standardized protocols and training are essential to improve diagnostic reproducibility across centers.

In EoE, 30–40% of untreated patients develop strictures. EoE requires long-term treatment to prevent fibrosis and strictures [32]. The association between EoE and Barrett’s esophagus, especially in GERD patients, is debatable [33]. Patients also have an elevated risk of other EGIDs, necessitating routine surveillance [34].

The precise etiology of EoG remains unclear, but it involves genetic predisposition, immune dysregulation, and environmental triggers such as food allergens and infections. It is frequently associated with atopic disorders, including asthma, allergic rhinitis, and EoE, suggesting an underlying immunologic mechanism. EoG can affect the mucosal, muscular, or serosal layers of the stomach.

EoG symptoms range from mild nausea, vomiting, early satiety, and bloating to severe hematemesis, weight loss, and malnutrition, especially with extensive mucosal involvement. Non-responsiveness to proton pump inhibitors (PPIs) may suggest EoG. Antral or pyloric narrowing from inflammation or fibrosis can cause delayed gastric emptying. Coexistence with EoE or gastroenteritis complicates diagnosis. The mucosal form is associated with inflammation and ulceration, while the muscular form may cause gastric outlet obstruction due to hypertrophy. The serosal form is the rarest but can lead to ascites and peritoneal involvement [35].

Physical examination findings are generally nonspecific but may include epigastric tenderness, particularly in cases with active inflammation or ulceration. Signs of malnutrition, such as weight loss or hypoalbuminemia, may be present. Allergic manifestations, including eczema, asthma, or urticaria, can be seen in patients with a systemic atopic predisposition.

Laboratory findings support EoG suspicion but are not diagnostic. Peripheral eosinophilia (> 500 eosinophils/µL) occurs in ~50% of cases, often with elevated serum IgE in atopic patients. Hypoalbuminemia may indicate protein-losing enteropathy. Negative stool studies help exclude parasitic infections. CT/MRI may show gastric wall thickening, nodular mucosa, and mural stratification, but these findings overlap with Ménétrier disease and gastric lymphoma.

Endoscopic findings are often nonspecific and may include thickened gastric folds, erythema, friability, and nodularity. Pseudo polyps occur in nearly 25% of cases [36]. Mucosal ulcerations, particularly in the antrum, may lead to GI bleeding.

Histological examination of gastric mucosal biopsies is critical for diagnosis (Figure 2). Findings include eosinophilic infiltration (> 25–30 eosinophils per HPF), which is a commonly used diagnostic threshold [17]. There is crypt hyperplasia and mucosal edema, reflecting chronic inflammation. Fibrosis and smooth muscle hypertrophy are seen, particularly in the muscular form of the disease. As eosinophils can also be seen in other conditions (e.g., parasitic infections, IBD), diagnosis should be made in conjunction with clinical and endoscopic findings.

EoG prognosis depends on severity and treatment response. While some achieve remission with dietary changes or corticosteroids, others develop chronic relapsing disease. Complications include gastric strictures, fibrosis, dysmotility, and protein-losing enteropathy, leading to hypoalbuminemia and edema. Rarely, severe, untreated cases may result in gastric perforation [34]. Early diagnosis and treatment with elimination diets, corticosteroids, or biologicals improve outcomes and prevent complications. EoG shows relapse rates above 50% after treatment discontinuation. Beyond structural complications, persistent symptoms and dietary limitations significantly impair quality of life, underscoring the need for long-term management strategies.

The pathogenesis of EoD is incompletely understood, but it is thought to result from immune-mediated hypersensitivity reactions. Food allergens and environmental triggers induce an eosinophilic inflammatory response, leading to epithelial damage, smooth muscle dysfunction, and fibrosis. Patients with EoD frequently have comorbid atopic disorders such as asthma, food allergies, and atopic dermatitis, suggesting a systemic allergic component.

EoD causes nonspecific GI symptoms like pain, nausea, bloating, and diarrhea. Severe cases lead to weight loss, anemia, and protein-losing enteropathy. Extensive eosinophilic infiltration can cause strictures and motility issues. Associated with allergies, EoD affects mucosal (malabsorption, ulcers), muscular (fibrosis, obstruction), and serosal (inflammation, ascites) layers.

Physical examination in EoD is often nonspecific. Some patients may have epigastric or periumbilical tenderness, while severe cases show pallor, weight loss, edema, or muscle wasting from malabsorption. Rarely, palpable masses suggest fibrosis or strictures, and atopic signs may be present [37]. Diagnosis relies on endoscopic and histological evaluation.

Laboratory tests in EoD assess eosinophilia, allergic markers, and malabsorption, but again are not diagnostic. Peripheral eosinophilia (> 500 cells/μL) may be present but does not always reflect severity [17]. Elevated IgE suggests an allergic component, while normal/mildly elevated CRP and erythrocyte sedimentation rate (ESR) help distinguish EoD from Crohn’s disease. Hypoalbuminemia, anemia, and vitamin deficiencies indicate malabsorption. Low fecal calprotectin differentiates EoD from IBD [37]. Diagnosis requires histological confirmation via duodenal biopsy.

Endoscopic findings in EoD are often nonspecific and may include mucosal erythema, edema, nodularity, granularity, white exudates, and erosions, while severe cases can present with ulcerations, mucosal atrophy, or strictures. However, the duodenal mucosa may appear normal in some patients, making multiple biopsies essential for diagnosis [38].

Since EoD lacks specific clinical and endoscopic features, histological examination of duodenal biopsies is essential for diagnosis. However, no universally accepted eosinophil threshold exists for defining EoD. Histological confirmation requires ≥ 20 eosinophils per HPF, often accompanied by crypt abscesses, degranulation, and villous atrophy (Figure 3). Submucosal or muscular involvement is seen in refractory cases. Since EoD can mimic celiac disease, Crohn’s disease, and H. pylori-associated duodenitis, biopsies from multiple segments of the duodenum are necessary for accurate assessment and elimination of other differential diagnoses [37, 39].

EoD prognosis depends on severity and treatment response. Some achieve remission with dietary changes or steroids, while others develop chronic or relapsing disease requiring long-term therapy [39]. Early diagnosis and treatment help prevent complications like fibrosis, strictures, and malabsorption.

EoJ is classified as a subtype of EGID, an immune-mediated disorder driven by an exaggerated Th2-type immune response. The infiltration of eosinophils into the jejunal mucosa is often triggered by food allergens in genetically predisposed individuals, leading to chronic inflammation, tissue remodeling, and epithelial barrier dysfunction. The absence of infectious or autoimmune triggers suggests a primary dysregulation of mucosal immunity, with increased intestinal permeability allowing allergens to provoke an inappropriate immune response [40].

EoJ is diagnosed by symptoms, eosinophilic infiltration, and exclusion of systemic causes. Peripheral eosinophilia is absent in ~20%, complicating diagnosis. Symptoms mimic inflammatory or obstructive disorders. EoJ can be classified into mucosal (malabsorption, bleeding), muscularis (obstruction, cramping), and serosal (ascites, eosinophilia) forms as in EoG [40].

Despite advances in diagnostic techniques, EoJ remains a largely retrospective and histopathological diagnosis. Laboratory tests, including complete blood counts and stool analysis, may not always confirm the disease. In cases with ascites, infectious cultures, cell counts, and cytological analysis are necessary to exclude other causes. While no universally accepted diagnostic criterion exists for eosinophilic ascites, eosinophil counts as high as 88% have been reported in some cases [40–42].

Physical examination in patients with EoJ typically reveals diffuse abdominal tenderness without guarding or rebound tenderness. Bowel sounds are usually present in all quadrants, and mild abdominal distension may be observed, depending on the severity of the disease. However, vital signs are generally normal, making clinical detection difficult in the absence of further diagnostic workup.

Endoscopic findings in EoJ are often nonspecific, with common features including erythema, erosions, and ulcerations. Upper GI endoscopy with biopsy confirms the diagnosis in approximately 80% of cases involving the mucosal layer [40]. However, in patients with deeper muscular or serosal involvement, endoscopic biopsies may appear normal, necessitating a laparoscopic full-thickness biopsy for definitive diagnosis [41].

Histological analysis plays a critical role in diagnosis (Figure 4). While eosinophils are present throughout the GI tract (except the esophagus) under normal conditions, significant eosinophilic infiltration in the jejunum suggests EoJ. No universally accepted eosinophil threshold per HPF exists for diagnosis, though some studies suggest that counts exceeding 100 eosinophils per HPF are indicative of disease [42]. Variability in biopsy interpretation underscores the importance of expert pathological opinion.

The prognosis for EoJ is generally favorable, with most patients responding well to dietary modifications and corticosteroid therapy. However, chronic cases may require long-term management with immunosuppressive agents to prevent recurrent inflammation and complications. Severe cases involving intestinal obstruction or perforation may necessitate surgical intervention.

EoI involves excessive eosinophil infiltration of the ileum, causing chronic inflammation and tissue damage. It arises from an exaggerated Th2 response to allergens, environmental factors, or microbiota in genetically predisposed individuals. Elevated IL-5 and eotaxin-3 drive eosinophil recruitment, leading to barrier disruption, fibrosis, and motility issues. Depending on the affected layer, it can cause malabsorption (mucosal), strictures (muscular), or eosinophilic ascites (serosal). The absence of infectious or autoimmune causes classifies it as a primary immune-mediated disorder.

EoI presents with nonspecific GI symptoms, often mimicking Crohn’s disease. These include abdominal pain (commonly in the right lower quadrant), diarrhea, nausea, bloating, and weight loss [45]. Severe cases may lead to intestinal obstruction, perforation, or strictures due to transmural inflammation and fibrosis.

Findings vary depending on disease severity. Many patients appear normal, but in symptomatic cases, abdominal tenderness (often in the right lower quadrant), distension, and signs of malnutrition (weight loss, pallor, edema from protein-losing enteropathy) may be noted. In severe cases, palpable masses may indicate fibrosis, stricture formation, or thickened bowel loops.

Peripheral eosinophilia is present in about 50% of cases but is not diagnostic [46]. Elevated serum IgE may indicate an allergic component. Mildly elevated CRP and ESR can help differentiate EoI from Crohn’s disease, which typically shows a stronger inflammatory response. Hypoalbuminemia and iron-deficiency anemia suggest malabsorption and chronic inflammation. Fecal calprotectin is typically low, unlike in IBD [47, 48].

Endoscopic findings in EoI are nonspecific and may include ileal mucosal erythema, edema, friability, nodularity, or erosions. Ulcerations or strictures may occur in severe cases. White exudates or thickened folds, resembling eosinophilic gastroenteritis, may be present [46, 47]. Since endoscopic abnormalities may be absent, multiple biopsies are crucial for diagnosis.

Histology confirms the diagnosis with increased eosinophilic infiltration (> 30 eosinophils per HPF) in the ileal mucosa, muscularis, or submucosa (Figure 5). Other features include crypt abscesses, eosinophilic degranulation, and fibrosis, which may contribute to stricture formation [47–49].

EoI shows relapse rates above 50% after treatment discontinuation. The prognosis varies based on severity and response to treatment. Mild cases may resolve spontaneously or with dietary modifications, while chronic cases require steroids, immunomodulators, or biologicals. Severe cases with strictures, perforation, or obstruction may need surgical intervention. Early diagnosis and management are key to preventing complications.

The exact cause is unclear, though ~75% of patients have a history of allergy or atopy [27]. Cow’s milk and soy proteins are common triggers in infants, but cases have also occurred in exclusively breastfed infants. In adults, the role of IgE is debated, with some studies suggesting mast cell involvement while others indicate a non-IgE-mediated mechanism via STAT6-dependent T-cell activation [48]. Eotaxins and IL-5 contribute to eosinophil recruitment. Experimental models suggest GI exposure leading to widespread disease, whereas lung sensitization may cause isolated esophageal involvement [49, 50].

Symptoms depend on the affected intestinal layer: mucosal involvement leads to malabsorption, diarrhea, and protein-losing enteropathy; transmural disease causes colonic wall thickening and obstruction; serosal involvement manifests as eosinophilic ascites (up to 95% eosinophils). Acute cases may present with intestinal obstruction, cecal volvulus, intussusception, or perforation.

Clinical findings vary by severity. Infants may have distension and irritability, while older patients show abdominal tenderness. Severe cases present with dehydration, weight loss, and malnutrition. Rarely, fibrosis causes palpable masses. As symptoms often overlap with other GI diseases, the gold standard diagnostic modality remains biopsy evaluation.

Diagnosing EoC requires both clinical and histological confirmation, ruling out other causes of colonic eosinophilia like infections or IBD. Peripheral eosinophilia (> 500 cells/µL) is absent in ~20% of cases, and stool tests help exclude parasitic infections. Allergic skin tests (AST) and radioallergosorbent test (RAST) can detect IgE-mediated allergies but lack sensitivity [51–54]. CT findings in children often show predominant involvement of the cecum and ascending colon, with minimal small bowel involvement. In adults, nonspecific CT findings in 60–70% of cases include colonic wall thickening, nodularity, and the “araneid-limb-like” sign due to diffuse mucosal thickening [46, 55]. These findings must be differentiated from inflammatory and infectious colitis.

The colonic mucosa is endoscopically normal in about 70% of cases [55]. In a retrospective series encompassing a study of 37 patients with EoC, mucosal involvement was noted in 33% of cases, most of which were segmental, while pancolitis was observed in only 11% of cases. The right and left hemi-colon were the most commonly affected (44% of cases). Mucosal lesions were non-specific: erythema in 88% of cases, edema with a decrease in mucosal vascularization in 50% of cases, erosions or even ulcerations in 63% and 50% of cases, respectively [56].

EoC lacks standardized diagnostic criteria, with interobserver variability complicating histological assessment. A threshold of > 40 eosinophils per HPF in at least two colonic segments is suggested (Figures 6, 7), though sensitivity (60%) and specificity (50%) remain low. Histological features include lamina propria eosinophilic infiltrates, intraepithelial eosinophils (76%), eosinophilic microabscesses (21%), submucosal involvement (6.6%), and degranulation (51%) [57]. A standardized protocol should assess eosinophil count, distribution pattern, presence of activation markers, fibrosis, and inflammatory changes.

EoC in infancy generally has a favorable prognosis, often resolving spontaneously within days. Over time, affected infants may even tolerate previously implicated foods. In contrast, EoC in young adults tends to follow a chronic course, characterized by alternating periods of activity and remission [58, 59]. EGIDs represent a spectrum of chronic, immune-mediated conditions characterized by dysregulated Th2 responses triggered by genetic susceptibility factors such as TSLP and CAPN14, in concert with environmental exposures including food allergens and microbes. Central cytokines—IL-5, IL-13, and eotaxins—mediate eosinophil recruitment, driving tissue injury and remodeling. Clinically, EGIDs frequently coexist with atopic diseases, with nearly three-quarters of patients reporting asthma, allergic rhinitis, or eczema. Among subtypes, EoE predominates, accounting for more than 90% of cases. Symptoms and complications vary by anatomic site and depth of involvement, ranging from mucosal inflammation to transmural or serosal disease. Endoscopic findings are often subtle or nonspecific, and peripheral eosinophilia is absent in up to half of patients, limiting the diagnostic utility of blood tests. Currently, histopathology remains the gold standard, though biopsy thresholds for defining eosinophilia differ across GI segments. Management typically begins with dietary elimination and corticosteroids, with biologics such as anti-IL-5 agents (mepolizumab, benralizumab) reserved for refractory cases, and surgical intervention indicated only for complications like obstruction or perforation. Prognosis is variable, spanning spontaneous resolution to the need for chronic maintenance therapy. High clinical suspicion remains essential, particularly in patients with persistent GI symptoms and an atopic background despite normal endoscopic appearances. Because EGIDs remain diagnoses of exclusion, systematic evaluation—including targeted laboratory tests, parasite and H. pylori screening, celiac serologies, and careful elimination of mimics such as GERD and IBD—together with biopsy-based confirmation, is critical to ensuring accurate diagnosis and appropriate management.

A brief summary of the various subtypes of eosinophilic GI diseases, including clinical semiology, endoscopic findings, diagnostic features, key differential diagnoses with distinguishing features, and management protocols, has been tabulated in Table 1. A comprehensive overview of their reported long-term outcomes is provided in Table 2.