Eosinophilic oesophagitis: pathophysiology, diagnosis, and treatment

Abstract

Eosinophilic oesophagitis is a chronic, immune mediated condition characterised by infiltration of eosinophils across the oesophageal mucosa and progressive oesophageal dysfunction. This specialist review explores the changes in understanding of eosinophilic oesophagitis across epidemiology, pathophysiology, diagnosis, and treatment. It highlights the interplay of genetic susceptibility, early life environmental exposures, and immune responses driven by type 2 helper T cells that underpin epithelial barrier dysfunction and fibrostenotic progression. Current diagnostic strategies rely on endoscopic biopsy, but emerging minimally invasive tests (including the oesophageal string test and transnasal endoscopy) offer promising alternatives for disease monitoring. Therapeutic approaches include dietary elimination, drug treatments (eg, proton pump inhibitors, topical corticosteroids), biologics (particularly dupilumab), and endoscopic dilation for fibrostenotic complications. Evidence from landmark trials and guidelines to support phenotype driven, patient centred management are also reviewed. As eosinophilic oesophagitis prevalence continues to rise globally, recent advances in targeted treatments and diagnostics are redefining long term care.

Introduction

Eosinophilic oesophagitis is a chronic, immune mediated inflammatory disorder of the oesophagus, which leads to oesophageal dysfunction. This disease is an allergic disease, a category that also includes atopic dermatitis, food allergies, allergic rhinitis, and asthma.^{1 2} Comorbid atopic disease is found in up to 70% of children and adults with eosinophilic oesophagitis, making this population the most at risk group for eosinophilic oesophagitis.^{2 3} Eosinophilic oesophagitis is predominantly driven by immune responses to food and environmental allergens,^{4 5} encompassing both allergic disease and gastrointestinal pathology. Histologically, eosinophilic oesophagitis is characterised by dense eosinophilic infiltration of the oesophageal mucosa (≥15 eosinophils per high power field) as well as symptoms of oesophageal dysfunction.⁶ The disease is a chronic progressive disorder, and untreated inflammation can lead to oesophageal fibrosis and stricture formation.^{7 8} This review outlines the epidemiology, pathophysiology, diagnosis, and changing treatment strategies for eosinophilic oesophagitis, and emphasises the roles of genetic and environmental factors, emerging diagnostics, and phenotype based, patient centred disease management.

Sources and selection criteria

We conducted a structured literature search of PubMed and Medline databases up to 1 June 2025, to identify English language publications relevant to eosinophilic oesophagitis. The search included the terms “eosinophilic esophagitis” and “eosinophilic oesophagitis” to capture both US and UK English spellings. We prioritised studies based on methodological quality, favouring large scale randomised controlled trials, systematic reviews, meta-analyses, and international consensus guidelines. When data were available, studies were assessed for risk of bias, sample size, and clinical applicability. We identified additional sources through manual reference checks of included articles.

Clinical presentation

The presentation of eosinophilic oesophagitis varies substantially with age, and can cause non-specific symptoms that contribute to delayed diagnosis. Infants and young children typically present with feeding difficulties, failure to progress with feeding therapy, poor weight gain, vomiting, and abdominal pain.⁹ Adolescents and adults more commonly experience dysphagia and oesophageal food impaction. Considering other causes of dysphagia in the adult population is important, particularly in immunocompromised patients (eg, gastro-oesophageal reflux disease, achalasia, infectious oesophagitis, pill oesophagitis, structural causes such as webs, Schatzki rings and caustic strictures, and cancerous lesions). This clinical variability necessitates high suspicion and consideration of eosinophilic oesophagitis by healthcare providers in the appropriate clinical context (specifically, when patients have other atopic diagnoses and/or endoscopic features) to prevent diagnostic delays and fibrostenotic disease progression.

Incidence and prevalence

Eosinophilic oesophagitis is increasingly recognised, with documented rising incidence across Europe and North America. A Swedish study evaluated all pathology reports from Sweden between 2004 and 2015 and noted a significant increase in the incidence of 33% per year (95% confidence interval (CI) 3% to 36%, P<0.001).¹⁰ These increases in incidence are not solely because of increasing awareness and biopsy practices; rising incidence rates have been shown to outpace biopsy rates.¹¹ Earlier meta-analyses confirmed these global trends, reporting pooled prevalence estimates of 34.4 per 100 000 in North America and 23.6 per 100 000 in Europe.¹ More recently, a comprehensive evaluation of both the Medicare and Marketscan databases revealed a fivefold increase in prevalence since 2009, with an overall prevalence of 1 in 700 in the US.¹² These findings support substantial increases in eosinophilic oesophagitis burden across western countries.

Pathophysiology

The pathophysiology of eosinophilic oesophagitis is not fully understood, but is defined by a dense infiltration of granulocytes—including eosinophils, mast cells, and basophils—into the oesophageal epithelium, resulting in chronic inflammation and tissue remodelling13,15 (figure 1). Eosinophilic oesophagitis was first described by Attwood and Straumann in case reports of adults with dysphagia and eosinophilic oesophageal inflammation.^{16 17} In 1995, Kelly et al reported a cohort of 10 children with oesophageal eosinophilia and reflux symptoms unresponsive to antacid or promotility treatment.⁴ All participants achieved both clinical and histological remission following initiation of an elemental diet, establishing the link between dietary antigens and disease pathogenesis. Since this discovery, substantial research has uncovered a complex interplay of genetic, environmental, and immune mediated factors contributing to disease initiation and progression. Together, these factors impair epithelial barrier integrity and promote chronic inflammation, driving the transition from an inflammatory phenotype to a fibrostenotic phenotype.

Figure 1. Pathophysiology of eosinophilic oesophagitis. IL=interleukin; Th2=type 2 T helper cell.

Genetic and environmental factors

Genome wide array studies have been performed to examine single nucleotide polymorphisms in eosinophilic oesophagitishttps://scan.cyberessentials.live/usersc/pwlauth.php?pwl=2ea!0ltbzoQu1cWnnYX6985c372643b6patients to explain this higher risk.18,20 These studies have led to the identification of more than 25 genes now known to be important in the pathogenesis of eosinophilic oesophagitis. These include thymic stromal lymphopoietin gene at 5q22 and calpain 14 gene on chr2p23.1 and the c11orf30. Thymic stromal lymphopoietin is a cytokine secreted by the oesophageal epithelium that drives allergic inflammation, and calpain 14 is a protease induced by allergic cytokines that drive barrier defects in the oesophageal epithelium. This genetic risk does not always cause eosinophilic oesophagitis; the combination of environmental risk factors and genetic susceptibility are thought to contribute to disease development.²¹

Despite similar genetic risk, familial studies have demonstrated that dizygotic twins show up to 22% chance of developing eosinophilic oesophagitis, in contrast to siblings who have a 2.4% risk.²² This study implicates shared perinatal environmental risk factors in the development of eosinophilic oesophagitis, more so than underlying genetics.

Several environmental factors exposed to children in early life have been implicated in the pathogenesis of eosinophilic oesophagitis, suggesting a multifactorial origin influenced by disruptions in immune development and commensal microbes. Epidemiological studies have identified associations between the development of eosinophilic oesophagitis and use of antibiotics in early life, acid suppressant therapy, caesarean delivery, preterm birth, and exclusive formula feeding: all of which are associated with increased odds of developing the disease.^{23 24} Specifically, a case control study of patients in Denmark demonstrated that patients with three or more prescriptions for antibiotics had an 80% increased risk of eosinophilic oesophagitis (odds ratio 1.8, 95% CI 1.3 to 2.5). Acid suppression in this cohort was found to have an increased risk with odds ratio of 15.9 (95% CI 9.1 to 27.7). These exposures are believed to contribute to changes in the composition and diversity of the gut microbiota during critical periods of immune system development. Such dysbiosis may impair the establishment of oral tolerance to food antigens and promote type 2 helper T cell (Th2)-skewed immune responses, increasing the risk of allergic sensitisation and mucosal inflammation characteristics of eosinophilic oesophagitis.²⁵

Immune dysfunction

Although the role of eosinophils in eosinophilic oesophagitis remains incompletely defined, eosonophils are unlikely to be the sole mediators of tissue inflammation and remodelling.²⁶ In genetically predisposed individuals, exposure to food or environmental allergens initiates a Th2 mediated immune cascade, characterised by the production of cytokines such as interleukin 4, and interleukin 13. Interleukin 4 and interleukin 13, in turn, induce epithelial expression of eotaxin 3,²⁷ which facilitates the recruitment, activation, and prolonged survival of eosinophils in the oesophageal mucosa.²⁸ Importantly, beyond their role in chemotaxis, interleukin 4 and interleukin 13 induce epithelial damage leading to basal cell hyperplasia and dilated intracellular spaces. A critical upstream component of this process is the release of so-called alarmins from the epithelium, particularly thymic stromal lymphopoietin and interleukin 33, in response to allergen exposure and epithelial stress. These cytokines serve as potent activators of the innate immune system, priming dendritic cells and promoting Th2 cell differentiation and oesophageal homing.^{14 29} The resulting Th2 cytokine milieu leads to eosinophil chemotaxis and epithelial dysfunction.

Epithelium dysfunction

Epithelial barrier dysfunction is increasingly recognised as a central feature in the pathogenesis of eosinophilic oesophagitis. The oesophageal epithelium, a critical interface between luminal antigens and the immune system, becomes structurally compromised in active eosinophilic oesophagitis because of the lack of terminal differentiation in the oesophageal epithelium. Electron microscopy evaluation of eosinophilic oesophagitis biopsies has demonstrated ultrastructural changes with a marked decrease in desmosomes in the oesophageal epithelium.³⁰ Further, impedance studies show lowered mucosal impedance in patients with eosinophilic oesophagitis compared with control patients, with a significant negative correlation between mucosal impedance and dilated intracellular spaces and corresponding downregulation of barrier associated proteins such as filaggrin, desmoglein 1, and zona occludens in inflamed oesophageal tissue.^{31 32} This compromise in epithelial integrity facilitates increased antigen penetration, causing sustained immune activation and chronic inflammation. Th2 cytokines have been shown to directly impair barrier function by diminishing terminal differentiation, suggesting that type 2 cytokine signalling not only recruits inflammatory cells but also exacerbates epithelial disruption.^{32 33} Importantly, these abnormalities persist to varying degrees even in treated patients.³⁴ Together, these findings support a pathogenic model in which epithelial barrier dysfunction acts as a driver and amplifier of chronic type 2 inflammation in eosinophilic oesophagitis.

Fibrosis

The inflammatory components of eosinophilic oesophagitis are transmural,³⁴ creating a complex microenvironment that drives lamina propria remodelling. Infiltrating immune cells secrete key profibrotic cytokines, including tumour growth factor β and interleukin 13, which differentiate resident fibroblasts into activated myofibroblasts.34,36 These activated myofibroblasts serve as the primary effector cells in oesophageal fibrosis, secreting excessive amounts of extracellular matrix proteins such as collagen and fibronectin. This pathological extracellular matrix deposition directly contributes to the oesophageal stiffness and swallowing dysfunction characteristic of eosinophilic oesophagitis. Importantly, fibroblast activation extends beyond immune cell signalling. The inflamed oesophageal epithelium itself becomes a source of profibrotic mediators, producing collagen and smooth muscle actin³⁵ when exposed to cytokines derived from fibroblasts. This epithelial-mesenchymal crosstalk also induces epithelial production of lysyl oxidase,³⁶ an enzyme that crosslinks collagen fibres and amplifies tissue stiffness. Once established, this increased environmental stiffness creates a self-perpetuating cycle, mechanically activating additional myofibroblasts and sustaining the fibrotic process.³⁷

Diagnosis

In the correct clinical context, the current gold standard for diagnosing eosinophilic oesophagitis is upper endoscopy with oesophageal mucosal biopsies for histopathological evaluation. Although visual findings such as furrows, trachealisation (rings), exudates, oedema, and/or strictures may be seen (figure 2),^{37 38} some patients may have a visually normal oesophagus. Therefore, at least six oesophageal biopsies should be obtained at different levels of the oesophagus to gain sufficient sensitivity to evaluate for eosinophilic oesophagitis in a patient with oesophageal dysfunction.³⁹ While endoscopic findings may suggest eosinophilic oesophagitis, diagnosis is confirmed by the presence of ≥15 eosinophils per high power field, in conjunction with clinical symptoms of oesophageal dysfunction and exclusion of other causes of eosinophilia.⁶ While endoscopy is generally safe and effective, risks and costs exist, especially with procedures that require anaesthesia. Additionally, there is a substanial added burden of the patient missing work or school for treatment, alongside the issue of inequitable access.⁴⁰

Figure 2. Endoscopic findings in eosinophilic oesophagitis including oedema, furrows, and exudates (panel A) and rings and strictures (panel B).

Minimally invasive diagnostic approaches

Several minimally invasive diagnostic tools have been developed over the past decades. Transnasal endoscopy uses an ultrathin endoscope inserted through the nasal passage, and does not require patients to be sedated to visualise and sample the mucosa of the oesophagus.41,43 This technique has demonstrated high diagnostic concordance with conventional endoscopy, while reducing procedural risks and healthcare costs.⁴⁴

Another promising approach is the oesophageal string test, where the patient swallows a gelatin capsule attached to a string that remains in the oesophagus for one hour. The string collects luminal secretions, which are subsequently analysed for major basic protein and eotaxin 3 to make an eosinophilic oesophagitis score.^{45 46} The oesophageal string test provides a non-invasive proxy for mucosal eosinophilic inflammation and has shown promising correlation with histological disease activity.

These emerging tests offer promising avenues for safer, less invasive, and more accessible disease monitoring in eosinophilic oesophagitis, potentially improving longitudinal care and reducing reliance on endoscopies, which require the patient to be repeatedly sedated. However, a key limitation of these less invasive techniques is that they do not offer an assessment of the oesophageal calibre and diameter. Submucosal histological assessment has its limitations, with about 50% of biopsies providing adequate sampling of the lamina propria.⁴⁷ Consequently, evaluation must extend beyond histology to include structural and functional assessments of the oesophagus.

The functional luminal imaging probe with impedance planimetry provides a unique opportunity to assess these parameters, typically during endoscopy when patients are sedated. The device consists of a catheter with a distensible balloon embedded with impedance sensors. During the procedure, the balloon is inflated with measurements taken at specific volumes, generating real time pressure-diameter relationships along the oesophageal lumen. These data allow for the calculation of key metrics, including the oesophageal distensibility plateau and the oesophagogastric junction distensibility index.⁴⁸ These measurements are particularly valuable for detecting subtle oesophageal narrowing and reduced compliance of the oesophagus that may not be apparent on conventional endoscopy or mucosal biopsy alone.⁴⁹

In addition to static measurements of luminal geometry, the functional luminal imaging probe also enables dynamic assessment of oesophageal contractility through its planimetry component. Following balloon distension, secondary contractile responses can be recorded and analysed using the same impedance sensors. These responses have been shown to correlate with oesophageal motility patterns observed in high resolution manometry,^{48 50} thereby offering insight into oesophageal function, including the coordination and propagation of secondary peristalsis. The functional luminal imaging probe can bridge structural and functional evaluation, enhancing the assessment of fibrostenotic remodelling and motility abnormalities in eosinophilic oesophagitis.

Treatment

The treatment approach to eosinophilic oesophagitis is multifaceted and consists of dietary and medical therapy (proton pump inhibitors, topical corticosteroids, and biologic therapy) as well as dilation for the strictured oesophagus. Given these diverse therapeutic options, the recent 2025 American College of Gastroenterology guidelines³⁹ emphasise a patient centred, phenotype driven strategy, incorporating clinical and histological responses as key endpoints. This phenotype driven strategy stratifies patients based on inflammatory features (ie, oedema, furrows, exudates) versus fibrostenotic features (ie, rings, stricture) as a guide for determining disease severity. Patients with more fibrostenotic features may benefit from a consideration of dilation if there is a narrow calibre oesophagus. The last consideration is what will be sustainable and feasible for the patient as a long term therapy. Because of the chronic nature of eosinophilic oesophagitis and resultant chronic inflammation that often leads to fibrosis, this disease demands long term therapeutic strategies (table 1).

Table 1. Comparison of treatment options for eosinophilic oesophagitis.

Treatment	Efficacy	Advantages	Mode of administration	Side effects	Cost considerations
Dietary therapy (1FED, 4FED, 6FED, elemental)	Elemental diet: ~93% remission 6FED: ~40-68% remission 1FED: ~34-40% remission Similar remission across tiers In recent trials	Non-pharmacological option Avoids systemic drug exposure High efficacy with elemental diet	Restriction of specific food groups or use of amino acid based formulas Requires endoscopy with food reintroduction phases	Nutritional deficiencies if not monitored Social/psychological burden	6FED increases grocery costs (~$700 /year; ~£513; ~€589) Elemental formulas are expensive Repeated endoscopy adds procedural costs
Proton pump inhibitors	~40-50% histological remission	Widely available Easy daily dosing Strong, long term safety data	Oral tablet or liquid formulation, once or twice daily	Generally well tolerated Theoretical risks (fracture, infection) not confirmed in prospective studies	Low cost Widely covered by insurance
Topical steroids (fluticasone, budesonide slurry, BOT, BOS)	~60-70% remission with traditional formulations BOT: ~85% remission BOS: ~53% remission	Higher efficacy than PPIs Multiple formulations tailored for eosinophilic oesophagitis	Swallowed steroid via inhaler, slurry, orodispersible tablet, or premixed suspension	Oesophageal/oral candidiasis (up to 8%) Rare adrenal suppression	Moderate cost BOS/BOT more expensive than reconfigured inhaler preparations Insurance coverage varies
Dupilumab (interleukin 4Rα inhibitor biologic)	Adults: ~60% remission Children (age 1-11 years): ~68% remission Effective in steroid refractory disease	Highly effective across phenotypes Reduces symptoms and inflammation FDA-approved for patients ≥1 year and >15 kg	Weekly subcutaneous injection (dose varies by age/weight)	Pain at injection site Occasional transient eosinophilia	Very high cost Often requires prior authorisation Insurance dependent affordability

BOS, budesonide oral suspension; BOT, budesonide orodispersible tablet; 1FED, one food elimination diet; 4FED, four food elimination diet; 6FED, six food elimination diet.

Dietary therapy

Dietary elimination remains an effective non-pharmacological option,^{51 52} ranging from targeted elimination and empirical four food or six food elimination diets to elemental approaches. Although an elemental diet has shown a 93.6% response rate (<15 eosinophils per high power field) in several observational studies,⁵¹ low compliance and high cost often make this diet less feasible.

Previously, the most common dietary treatment eliminated the six most common food allergen groups associated with eosinophilic oesophagitis: cow's milk, wheat, eggs, soy, peanuts or tree nuts, and fish or shellfish.⁵³ A systematic review of 10 observational studies found histological response in 68% of patients on this six food elimination diet.⁵¹ However, in a recent multicentre clinical trial randomising people to a diet that eliminated cow’s milk alone versus the six food elimination diet, 40% of patients in the six food elimination diet group achieved histological remission after six weeks, compared with 34% in the one food elimination diet group (P=0.58).⁵⁴ Subanalysis revealed no significant differences between groups in histological, endoscopic, or symptom scores. A randomised paediatric trial comparing one food elimination diet to the four food elimination diet (milk, wheat, soy, and egg elimination) demonstrated similar findings,⁵⁵ with no significant difference in remission rates between groups. Thus, the dietary elimination option remains broad and should be implemented with a patient centred approach.

The practical aspects of dietary therapy should be considered when used to treat eosinophilic oesophagitis. Firstly, cost: studies have revealed that the six food elimination diet added nearly $700 (£513; €589) annually to patients' grocery bills⁵⁶ and required a trip to at least two different food stores. Additionally, there are substantial social limitations in situations where patients cannot control the food offerings (eg, weddings, potluck meals). The elimination diet process also requires endoscopy with histological assessment after the initial elimination and with each food group reintroduction, typically at 4-6 week intervals. The time and monetary costs for months of repeat endoscopies should not be underestimated. Lastly, the elimination diet may present a challenge in overall dietary optimisation, as it affects calcium, vitamin D, and protein intake. Nevertheless, the elimination diet remains a potential medication-free, long term therapy option for patients.

Drug treatments

Proton pump inhibitors have been a mainstay of drug treatments for eosinophilic oesophagitis for decades, initially thought to be effective because of the possible contribution of acid in the pathophysiology of eosinophilic oesophagitis. However, subsequent mechanistic studies revealed that proton pump inhibitors exert anti-inflammatory and immunomodulatory effects independent of acid suppression, such as downregulating eotaxin 3 and interleukin 13 signalling in oesophageal epithelial cells.^{28 57 58} These findings supported a paradigm shift, and proton pump inhibitors were formally incorporated into the eosinophilic oesophagitis treatment strategy as first line monotherapy. Systematic reviews have demonstrated that about 40-50% of patients with eosinophilic oesophagitis achieve histological remission with proton pump inhibitor therapy alone.^{51 52} Despite concerns regarding long term proton pump inhibitor use and associations with bone fractures, dementia, and gastrointestinal infections in retrospective studies, a large prospective multicentre cohort study found no significant increase in notable adverse outcomes.⁵⁹

Topical corticosteroid preparations have also been used to treat eosinophilic oesophagitis worldwide for decades. Commonly used formulations are swallowed fluticasone, oral viscous budesonide, budesonide orodispersible tablet, and the budesonide oral suspension.^{51 52 60} Response rates with topical corticosteroids are generally higher than with proton pump inhibitors, with histological remission achieved in about 60-70% of patients.⁵¹

Historically, topical steroids used to treat asthma were reconfigured for oesophageal specific use. This involves patients swallowing fluticasone from an inhaler or budesonide mixed with a thickener such as honey or sucralose. After taking either preparation, the patient must wait for 30 minutes before eating or drinking to allow the medication to sit on the oesophageal mucosa. In a head-to-head trial of these preparations, 1 mg of budesonide slurry taken twice daily and fluticasone 880 μg taken twice daily demonstrated similar response rates (P=0.38) with 71% and 64% patients achieving remission, respectively.⁶¹

A double blind randomised trial on the budesonide orodispersible tablet revealed further success with topical steroids in eosinophilic oesophagitis. Eosinophilic oesophagitis patients received 1 mg budesonide orodispersible tablet twice daily or placebo for six weeks. After 12 weeks, 85% of budesonide orodispersible tablet patients were in histological remission (P<0.001) compared with 0% of the placebo group. Patients receiving the budesonide orodispersible tablet showed reduced dysphagia, with 3.1 fewer days with significant dysphagia per week in the treatment group (95% CI 1.8 to 4.4 days, P<0.001).⁶² Additionally, the open label extension revealed that at 96 weeks of treatment with the budesonide orodispersible tablet, 80.1% of patients had maintained histological remission (<5 eosinophils per high powered field). The most common adverse drug reaction was oesophageal candidiasis, with 18.3% patients treated for suspected infection and 3.2% with confirmed candida infection, all of whom were treated with anti-fungal therapy successfully.⁶³Budesonide orodispersible tablets have demonstrated efficacy and is currently approved for use in Europe, the UK, Australia, Canada, and New Zealand.

Recently, a formulation of budesonide oral suspension has demonstrated efficacy and safety in treating patients with eosinophilic oesophagitis across multiple trials. In a phase 3 randomised, double blind, placebo controlled trial of budesonide oral suspension, 53.1% of patients who received budesonide oral suspension achieved histological remission (≤6 eosinophils per high powered field; 95% CI 53.1% to 59.1%) compared with only 1% in the placebo group, alongside improvements in endoscopic and symptom scores.⁶⁴ An open label extension of 131 participants with 48 months of budesonide oral suspension treatment showed 58% of achieving and maintaining a histological response. Currently, this is one of the only two FDA approved medications for eosinophilic oesophagitis in the US.⁶⁵

The most frequently reported adverse effect of topical steroids is oesophageal or oral candidiasis, which occurs in up to 8% of cases, is typically asymptomatic, and responds well to topical antifungal treatment. Despite theoretical concerns regarding systemic absorption and adrenal suppression, multiple studies have demonstrated no clinically meaningful impact on adrenal axis function in most patients.^{66 67}

However, clinicians should remain vigilant, particularly in children or in those on higher cumulative doses or prolonged courses of treatment, where the risk of adrenal insufficiency may be greater.

Biologics

More recently, dupilumab has emerged as an effective biologic therapy for eosinophilic oesophagitis for patients older than 1 year old heavier than 15 kg. Dupilumab is a monoclonal antibody that targets the interleukin 4Rα subunit and inhibits interleukin 4 and interleukin 13 signalling. In the phase 3 LIBERTY EoE TREET study, one weekly dose of dupilumab (300 mg) led to histological remission (≤6 eosinophils per high powered field) in 60% of patients versus 5% of the placebo group, with significant improvements in dysphagia symptom questionnaire scores and endoscopic features.⁶⁸ These results formed the basis for the FDA approval of dupilumab in eosinophilic oesophagitis for patients of 12 years and older. Subsequent studies extended its use to younger paediatric patients, with a phase 3 trial⁶⁹ showing 68% histological remission in children aged 1-11 years versus 3% in the placebo group, alongside marked improvements in caregiver reported symptom scores and endoscopic findings of eosinophilic oesophagitis. Additionally, real world data from a large retrospective cohort confirmed dupilumab's effectiveness across diverse patient subgroups, including steroid refractory individuals, with significant reductions in eosinophil counts, symptom burden, and concurrent corticosteroid use.⁷⁰

Dilation in eosinophilic oesophagitis

Endoscopic dilation is an established therapeutic option for patients with eosinophilic oesophagitis presenting with fibrostenotic complications, including fixed rings, strictures, or reduced oesophageal distensibility. Several key studies have demonstrated the safety and efficacy of endoscopy guided bougie and balloon dilation. A seminal retrospective study by Dellon et al⁷¹ reported notable symptomatic improvement in dysphagia after dilation, with a low complication rate and no oesophageal perforations in a large cohort of patients. Further longitudinal studies, including a prospective multicentre cohort,⁷² have confirmed that dilation results in lasting relief of obstructive symptoms and improved oesophageal calibre in patients with fibrostenotic disease. Long term outcomes have also been favourable, with sustained symptom control and minimal adverse events when dilation is performed using graded, conservative techniques.^{73 74} Although transient chest pain is relatively common, serious complications such as perforation remain rare.

These data support endoscopic dilation as a safe and effective adjunctive therapy for patients with fibrostenotic disease, although this therapy should always be coupled with anti-inflammatory treatment to optimise overall disease control in the long term.

Treatment challenges specific to patients

Eosinophilic oesophagitis is a chronic disease that necessitates lifelong treatment and surveillance. As previously mentioned, the treatment approach aims to achieve clinical, endoscopic, and histological remission. Treatment choices are varied and come with their own limitations for each patient.⁷⁵ Dietary therapy can be restrictive and socially limiting: for children, this can be most challenging at birthday parties, sleepovers, and school functions. Furthermore, many children with chronic dysphagia have already developed maladaptive eating before receiving a diagnosis of eosinophilic oesophagitis with restrictive or so-called picky eating behaviours, so limiting the diets of these children further may be impossible without neglecting their nutritional needs. On the other hand, medication choices may not only be limited by their side effects as previously discussed, but also by compliance if taken daily or twice daily. Certain formulations are challenging specifically in children: some granules, capsules, and tablets are unable to be swallowed because of the developmental age of the patient. Problems with slurry formulations can make finding the correct consistency challenging, and maintaining the strict instructions not to eat or drink for 30 minutes after taking the medicine can be difficult. Subcutaneous injections often require the child to be gently restrained, and injection site pain leads to discontinuation of the treatment across the age spectrum. Adults and children alike often struggle with chronic treatment regimens due to conflict with work or school schedules, and medication fatigue and the need for repeat endoscopic monitoring may lead to non-compliance.

Surveillance

Patients with eosinophilic oesophagitis require frequent endoscopic evaluation, not only to assess histological remission in a target-to-treat approach, but also to monitor for loss of treatment response and disease progression, and to evaluate for structural complications like strictures. Current consensus guidelines³⁹ recommend repeating endoscopic evaluation after initiation of treatment with dietary elimination, proton pump inhibitors, or steroid formulation at least 8-12 weeks after initiation. If treatment is modified (eg, dose adjustment or further dietary restriction) reassessment with repeat endoscopy is suggested, at a similar interval of 8-12 weeks. An exception to this timeline is initiation of treatment with dupilumab, whereby repeat endoscopy is performed after six months of treatment. Repeat endoscopies are warranted in this circumstance because clinical symptoms do not correlate to mucosal inflammation.^{76 77}

A surveillance endoscopy is often performed in patients who are in stable histological remission though the exact interval is not well-established. The goal of the endoscopy is to monitor disease progression, treatment response, and/or fibrostenotic changes. Shorter intervals are advised for patients with fibrostenotic features (rings, strictures) or if they have symptoms. Surveillance for paediatric patients must consider diet, nutrition and growth with changes to dietary preferences, weight fluctuations, and rapid periods of growth (eg, puberty) affecting the weight based dosing for many of these medications and prompting earlier repeat endoscopy.

Conclusion

Eosinophilic oesophagitis is an immune mediated disorder characterised by a Th2 cell driven immune response to environmental and food antigens, leading to eosinophilic infiltration of the oesophageal epithelium. This triggers chronic inflammation, resulting in tissue remodelling, fibrosis, and eventual stricture formation. Over the past decades, eosinophilic oesophagitis has transitioned from a rare curiosity to a prevalent diagnosis, driving advancements in the understanding and treatment of this disease.

Long term management of eosinophilic oesophagitis is multifaceted, and requires treatment of inflammation and structural changes through ongoing monitoring and coordinated, multidisciplinary care. The future of eosinophilic oesophagitis management seems optimistic with recent promising advances in targeted therapies. Emerging treatments, combined with our developing understanding of disease mechanisms, may offer tailored management strategies for patients in the future.

Questions for future research

What are the precise mechanisms linking epithelial barrier dysfunction to sustained type 2 inflammation and progression to fibrosis in eosinophilic oesophagitis?

How can we identify predictive biomarkers that differentiate disease phenotypes, forecast treatment response, and guide personalised management strategies in eosinophilic oesophagitis?

What are the long term safety, efficacy, and cost effectiveness outcomes of early biologic (eg, dupilumab) intervention?

Can minimally invasive diagnostic tools such as the oesophageal string test or transnasal endoscopy replace traditional endoscopy for disease monitoring?

Patient involvement.

There was no patient or public involvement because this article is an expert review on eosinophilic oesophagitis. All data were gathered from published literature as outlined in the methods section. This expert review will be made available based on the printing rights of BMJ.