Eosinophilic oesophagitis

• Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated disease of the oesophagus in which a T-helper 2 (Th2) response to food (and sometimes aero-)antigens floods the oesophageal lining with eosinophils.
• It has become a leading cause of solid-food dysphagia and food impaction in both children and adults; prevalence worldwide is now of the order of 40 per 100,000 people. ^[3]
• Adults usually describe food "going down slowly" or sticking; children present with vomiting, feeding refusal and failure to thrive. The diagnosis rests on endoscopy with biopsies showing at least 15 eosinophils per high-power field. ^[1][2]
• PPIs, swallowed topical corticosteroids (such as budesonide or fluticasone), and diet are the three established first-line treatments; the biologic dupilumab is reserved for severe, fibrostenotic or treatment-refractory disease. ^[1][2][3]
• Untreated EoE progresses from inflammation to fixed rings and strictures, so early diagnosis and continued anti-inflammatory treatment matter as much as symptom relief. ^[4]

By the end of this page you should be able to:

1. Explain why type 2 inflammation and barrier dysfunction in EoE produce dysphagia and food impaction.
2. Recognise the age-dependent presentation and describe the adaptive eating behaviours adults develop.
3. State the diagnostic standard (symptoms plus biopsy) and the biopsy, threshold and endoscopic scoring rules.
4. Compare PPI, topical corticosteroid, elimination-diet and dupilumab therapy by suitability, expected histologic response and safety.
5. Outline follow-up and endoscopic thresholds for assessing treatment response.
6. Adapt management to children, older adults and low-resource settings.

EoE is not simply reflux. Gastro-oesophageal reflux disease (GORD) can produce mild eosinophilia, but the two conditions coexist and share pathways, and current concept papers treat PPI-responsive oesophageal eosinophilia as a subtype of EoE rather than a separate diagnosis. ^[4] The driver in EoE is a delayed, non-immunoglobulin E (non-IgE) allergic reaction to antigens, most often foods, with type 2 inflammation and oesophageal remodelling. ^[2]

EoE has risen from obscurity to a common diagnosis in about three decades. A 2023 systematic review and meta-analysis of population studies reported a pooled global prevalence of roughly 40 per 100,000 people and an incidence of roughly 5.31 per 100,000 person-years. ^[3] In the general population, histopathology-focused reviews put prevalence at closer to 30 to 52 per 100,000. ^[4] An Italian pediatric guideline gives Western estimates of up to 20 per 100,000 per year incidence and 1 per 1,000 prevalence, and notes that the annual burden keeps increasing. ^[1] These figures vary between studies and between adults and children, and the incidence appears to be outpacing improvements in disease recognition. ^[1][3]

Two demographic patterns matter at the bedside:

• Male sex. Males are affected roughly 2 to 3 times more often than females in pediatric series, and between 2 and 10 times more often in some adult referral populations. ^{[1][4] [2]}
• Atopy. Two-thirds of children with EoE have a history of atopy, and EoE sits in the type 2 family with asthma, allergic rhinitis, atopic dermatitis and chronic rhinosinusitis with nasal polyps. ^[1][2] The odds of these comorbidities in EoE versus controls range from 2.8 to 5.1 in pooled data. ^[1]

Presentation is also highly conditional on why the endoscopy was done: when endoscopy is performed for dysphagia or food impaction, EoE is found in 63 to 88% of children and in 10 to 15% of adults. ^[4] That is the clinical clue for a student: in a young person with these symptoms, EoE is not rare.

EoE is multifactorial: genetic susceptibility plus early-life and environmental exposure produces a chronic antigen-driven process.

• Genetic. Risk is familial and twin studies support strong clustering; variants in barrier genes (filaggrin, desmoglein 1, calpain 14) and Th2 signalling molecules (eotaxin-3, periostin, TSLP) are implicated. ^[3]
• Environmental early-life factors. Formula feeding, cesarean delivery, preterm birth, neonatal intensive care, and early exposure to antibiotics, acid suppressants and histamine-2 receptor blockers have all been associated with later EoE, plausibly through microbiome effects. ^[1][3]
• Atopic constitution. IgE-mediated food allergy, asthma and atopic dermatitis frequently coexist. ^[2]
• Antigen. The disease is driven by food antigen exposure; cow's milk, wheat and egg are the most common triggers in dietary studies. ^[3]

There is no known safe "lifestyle" prevention, and the rising incidence suggests that awareness alone does not explain the whole trend. ^[1][3]

Everything in EoE follows from three linked steps: a leaky barrier, type 2 inflammation, and progressive remodelling.

1. Barrier dysfunction. The oesophageal epithelium in EoE shows reduced desmoglein-1 and E-cadherin, so allergens penetrate more easily; epithelial cells then release alarmins such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and IL-25. ^[3]
2. Th2 inflammation. These alarmins activate antigen-presenting cells and type 2 innate lymphoid cells; naive T cells become Th2 cells that release IL-4, IL-5 and IL-13. IL-13 drives eotaxin-3 (CCL26), which recruits eosinophils via the CCR3 receptor; IL-5 supports eosinophil growth and activation. Mast cells and basophils add histamine and leukotrienes. ^[3]
3. Remodelling. Chronic inflammation leads to basal zone hyperplasia, dilated intercellular spaces, subepithelial fibrosis and eventually fixed rings and strictures; eosinophils can persist focally even when symptoms are mild. ^[3][4]

This disconnect between symptoms and histology is clinically important. Patients adapt their eating behaviour for years (extra chewing, drinking water with bites, avoiding fibrous foods), so they may not report dysphagia until a stricture is significant. ^[2] Functional luminal imaging and endoscopic scoring therefore assess disease more objectively than symptom scores alone. ^[3]

Adults and adolescents usually report:

• solid-food dysphagia, often episodic;
• food impaction, especially with meat and bread;
• adaptive eating behaviour (drinking with meals, cutting food small, prolonged chewing, avoiding hard textures, difficulty swallowing tablets); ^[2]
• chest pain or heartburn.

Infants and young children present more vaguely with reflux-like symptoms, vomiting, nausea, abdominal pain, food refusal and failure to thrive; dysphagia and impaction appear in school-age children. ^[1]

Atopic background. Asthma, allergic rhinitis, atopic dermatitis or IgE-mediated food allergy is common; a family history of dysphagia or EoE also raises suspicion. ^[2]

There is often nothing to find physically. The value is in the dietary and atopic history and in testing for coexisting allergic disease. Weight may be low in children. Abdominal and chest examinations are usually normal unless a complication has occurred.

A food bolus stuck in the oesophagus, or the inability to swallow saliva, is an emergency needing endoscopic removal; taking oesophageal biopsies at the same time is strongly encouraged. ^[2]

Endoscopy is required for diagnosis regardless of how normal the mucosa looks. Characteristic but not mandatory findings include oedema, fixed rings, white exudates, linear furrows, strictures and fragile "crepe-paper" mucosa. ^[2][4] The standardised way to report them is the EoE Endoscopic Reference Score (EREFS), which splits features into inflammatory (oedema, exudates, furrows) and fibrostenotic (rings, strictures) components. ^[2][3][5]

When EREFS is used to monitor treatment, improvement can be quantified: in the LIBERTY EoE TREET programme, dupilumab 300 mg weekly improved the worst-observed-region EREFS total score by a mean of 2.17 points compared with placebo at 24 weeks. ^[5]

• Threshold: at least 15 eosinophils per high-power field (per 0.3 mm2; equivalent to 60 eosinophils per mm2 in the international consensus definition). ^[1][2][4]
• Sampling: a minimum of 6 biopsies from at least 2 levels (distal, mid and proximal oesophagus); Canadian consensus phrasing asks for at least 2 biopsies per level from at least 2 segments, giving 4 to 6 in total. ^[1][2]
• Ancillary findings that strengthen the diagnosis: eosinophil microabscesses (clusters of at least 4 eosinophils), superficial layering, basal zone hyperplasia, dilated intercellular spaces, dyskeratotic cells and lamina propria fibrosis. ^[4]
• Scoring: the Histologic Scoring System (HSS) grades eight features from 0 (normal) to 3 (maximum), to a maximum of 24, capturing inflammation and remodelling more completely than eosinophil counts alone. ^[4]
• PPI handling: stop PPIs 3 to 4 weeks before biopsy collection to avoid transient suppression of eosinophilia. ^[1]

• Allergy testing (skin prick, specific IgE, patch tests) is useful for concurrent IgE-mediated food allergy and atopic comorbidity, but should not be used to select empirical elimination diets for EoE: it has low to moderate predictive value for true EoE trigger foods. ^[1][2][3]
• Blood tests and imaging are not diagnostic but help exclude mimics and assess nutrition.
• Non-invasive tools such as the oesophageal string test, Cytosponge and transnasal endoscopy are emerging and are reserved to centres with experience; they do not yet replace biopsy. ^[3]
• Motility testing is reserved for atypical presentations or poor response.

The diagnosis requires all three elements: symptoms of oesophageal dysfunction, oesophageal biopsy with at least 15 eosinophils per high-power field, and exclusion of other causes of eosinophilia. ^[1][2][4] A PPI trial is not needed for diagnosis. ^[1][2]

For historical context, high-dose PPI taken for 8 to 12 weeks can still be used as a therapeutic trial (remission in 30 to 50% of patients), because PPI-responsive oesophageal eosinophilia is now considered part of the EoE spectrum and PPIs have anti-inflammatory effects beyond acid suppression. ^[3][4]

The three elements of care are: control symptoms, suppress inflammation, and watch for fibrostenotic change. Shared decision-making with the patient (and, for children, the family) is central, because drug, diet and procedural options differ in efficacy, burden and acceptability.

PPIs are the preferred first-line in mild disease in the Italian 2025 pediatric guideline, at 2 mg/kg/day. ^[1] They work partly by reducing acid, and partly through anti-inflammatory effects on the oesophageal epithelium; symptom and histologic remission rates are 30 to 50% within 8 to 12 weeks. ^[3] In adults, high-dose regimens (often twice daily) are used; exact drug and dose should follow local guidance rather than a single global rule. Stopping PPIs is a shared decision because maintenance helps prevent fibrosis. ^[2][4]

These deliver drug to the mucosa with minimal systemic absorption and are the most reliably effective first-line class for histologic remission (60 to 95%). ^[3] Options include:

• budesonide orodispersible tablet, approved in Canada for adults; ^[2]
• viscous swallowed budesonide (off-label); ^[2]
• fluticasone metered-dose inhaler with the dose swallowed (off-label). ^[2]

Oral systemic corticosteroids are not recommended for routine EoE, because relapse is rapid and steroid toxicity follows long-term use. ^[2]

Because EoE is antigen-driven, removing the offending food can induce remission. Current consensus recommends a step-up approach rather than starting with six-food removal: begin with one (cow's milk) or two foods (milk plus wheat), then step up if needed, with dietitian support. ^[2][3] In the pooled data, cow's milk was the most common trigger (70.5%), followed by wheat (48.0%) and egg (27.6%); overall histologic remission with empirical elimination was 53.8%. ^[3] Elemental amino-acid formula achieves 90 to 95% remission but is unpalatable, expensive and usually requires tube feeding, so it is reserved for refractory cases. ^[3]

Prolonged dietary exclusion carries a real hazard in atopic patients: avoiding a food for long periods can permit IgE-mediated sensitisation and anaphylaxis on re-exposure, so transition periods and re-introduction should be supervised and allergy input sought where needed. ^[2]

Dilation relieves a stricture or narrow calibre but does not treat the underlying inflammation; it should therefore be used as an adjunct only, with medical or dietary therapy continued. ^[2] Most narrowings can be dilated, but perforation risk, although small, is real in a fragile oesophagus.

Dupilumab blocks the IL-4/IL-13 axis through the IL-4 receptor alpha subunit. It is licensed for EoE from 1 year of age in patients weighing at least 15 kg, at weight-based doses (200 mg every 2 weeks below 30 kg; 300 mg every 2 weeks for 30 to below 40 kg; 300 mg once weekly for 40 kg or more), and is generally reserved for disease refractory to, or intolerant of, standard therapy, or where another approved severe type 2 condition is present. ^[6] In LIBERTY EoE TREET it produced histologic remission in 60% versus 5% on placebo, with large peak eosinophil reductions and sustained dysphagia, EREFS and dispensability improvements through 52 weeks; post hoc data show improvements in both inflammatory and fibrostenotic endoscopic components. ^[3][5]

Endoscopy with biopsies should be repeated after a change in management, ideally at 6 to 12 weeks (many guidelines phrase 8 to 12 weeks). ^[1][2] Maintenance treatment is typically continued for years; the optimal duration once remission is achieved is not well defined and is guided by severity, phenotype and shared decision-making, because fibrostenotic risk accumulates silently. ^[2][4] Long-term monitoring every 1 to 2 years is advised even when symptoms have resolved. ^[1]

• Strictures and a narrow-calibre oesophagus from fibrostenotic remodelling; risk rises with untreated or delayed diagnosis. ^[2][4]
• Food impaction, sometimes needing endoscopic removal, and rarely perforation. ^[2][4]
• Growth failure and feeding aversion in children. ^[1]
• Malnutrition and vitamin or micronutrient deficiency on very restrictive diets. ^[2]
• Psychosocial burden of chronic dysphagia, including anxiety around eating. ^[2]

With appropriate therapy EoE usually achieves symptom and histologic control, and a disease-modifying strategy can slow or stop fibrostenotic progression, although long-term remission varies between individuals. ^[2][3] Cessation of treatment usually leads to recurrent inflammation and remodelling, which is why EoE is managed as a chronic disease rather than treated episodically. ^[3]

• Children. School presentation may be non-specific. Endoscopy should be performed in a pediatric setting where possible. Dietary steps dominate in atopic children; weight-based PPI dosing (2 mg/kg/day) applies. ^[1]
• Adolescents transitioning to adult care. This is a high-risk period for loss to follow-up and worsening fibrosis. ^[2]
• Older adults. Fibrostenotic phenotypes and comorbid reflux are more common, and polypharmacy changes PPI interactions; endoscopic dilation may be needed earlier. ^[2][4]
• Pregnancy. Safety data for swallowed topical steroids and PPIs are reassuring, and dupilumab's use in pregnancy should be discussed with obstetrics and gastroenterology; the priority is maintaining nutrition and avoiding impaction. ^[2]

• EoE is a chronic type 2 immune-mediated oesophageal disease driven by barrier dysfunction and allergic (usually food) antigen exposure.
• Adults present with solid-food dysphagia, food impaction and adaptive eating behaviour; children present with vomiting, feeding refusal and failure to thrive.
• Prevalence has risen to about 30 to 52 per 100,000, and the disease is roughly 2 to 3 times more common in males.
• Diagnosis requires symptoms plus at least 15 eosinophils per high-power field on biopsy; at least 6 biopsies from 2 or more levels are taken even if the mucosa looks normal.
• A PPI trial is no longer needed for diagnosis; PPIs (30 to 50% histologic remission at 8 to 12 weeks) are a first-line treatment.
• Swallowed topical corticosteroids achieve 60 to 95% histologic remission; oral systemic steroids are avoided.
• Diet is antigen-directed; step up from one food (cow's milk) or two, with dietitian support; elemental diet is reserved for refractory disease.
• Dupilumab is licensed for EoE from 1 year of age (body weight at least 15 kg), with weight-based dosing (300 mg weekly only at 40 kg or more), and is generally reserved for refractory or fibrostenotic cases. ^[6]
• Endoscopy is repeated 6 to 12 weeks after a change of treatment; monitoring continues every 1 to 2 years even if asymptomatic.
• Untreated EoE progresses from inflammation to fixed rings, strictures and food impaction, so treat early and continue therapy.

• Gastro-oesophageal reflux disease
• Functional dysphagia
• Atopic disorders and type 2 inflammation
• Endoscopic biopsy and histologic scoring
• Food allergy and elimination diets