Introduction
Eosinophilic esophagitis (commonly abbreviated as EoE) is a chronic, immune‑mediated disorder of the esophagus that is characterized by a persistent infiltration of eosinophils into the esophageal epithelium. The disease manifests as symptoms related to esophageal dysfunction, including dysphagia, food impaction, and, in pediatric patients, feeding difficulties and failure to thrive. Clinical awareness has grown rapidly over the past three decades, leading to increased recognition of the condition across age groups and geographies. The pathogenesis of EoE involves a complex interplay of environmental triggers, genetic predisposition, and dysregulated immune responses. Modern diagnostic protocols combine endoscopic evaluation with histologic assessment and exclusion of other eosinophilic gastrointestinal diseases. Therapeutic strategies encompass dietary elimination, topical steroids, systemic medications, and procedural interventions such as dilation. Ongoing research continues to refine the understanding of disease mechanisms and to develop targeted treatments.
History and Discovery
Early Observations
Clinical descriptions of esophageal eosinophilia date back to the early twentieth century, when pathologists noted eosinophilic infiltrates in biopsy specimens from patients with dysphagia. However, these findings were rarely distinguished from allergic reactions or other eosinophilic gastrointestinal disorders. It was not until the 1970s that clinicians began to recognize a distinct disease entity, particularly in pediatric populations with food allergy backgrounds.
Formal Recognition
The term “eosinophilic esophagitis” entered the medical lexicon in 1993, following a pivotal study that correlated esophageal eosinophilia with allergic phenotypes and dietary triggers. Subsequent consensus statements from gastroenterology societies in the early 2000s established diagnostic criteria, emphasizing the need for endoscopic biopsies and exclusion of other causes of esophageal eosinophilia. These milestones transformed EoE from a pathological curiosity into a recognized clinical syndrome, prompting the development of evidence‑based management guidelines.
Pathophysiology and Classification
Immunologic Basis
Central to EoE pathogenesis is a Th2‑dominant immune response. Allergen exposure, often through the gastrointestinal tract or inhalation, activates antigen‑presenting cells that release cytokines such as interleukin‑13 (IL‑13) and interleukin‑4 (IL‑4). These cytokines drive eosinophil recruitment, activation, and survival within the esophageal mucosa. The resulting eosinophilic inflammation leads to tissue remodeling, fibrosis, and the clinical manifestations of dysphagia.
Diagnostic Criteria
Diagnostic standards require a combination of clinical, endoscopic, and histologic findings. Endoscopically, the esophagus may display rings, furrows, exudates, or strictures. Histologically, a threshold of at least 15 eosinophils per high‑power field in the esophageal mucosa is typically required, after excluding other etiologies such as gastroesophageal reflux disease, infections, or medication‑induced eosinophilia. The criteria also consider the response to empiric therapies and the presence of atopic comorbidities.
Subtypes and Clinical Variants
Based on symptomatology and disease course, EoE is often divided into two major phenotypes: the “food‑intolerant” or “pediatric” phenotype, characterized by feeding aversion and growth concerns, and the “dysphagia” or “adult” phenotype, presenting primarily with swallowing difficulties. A third, less common variant involves esophageal motility disorders, where esophageal dysmotility coexists with eosinophilic infiltration. Understanding these subtypes assists clinicians in tailoring diagnostic work‑up and therapeutic approaches.
Clinical Presentation
Symptoms in Children
Children with EoE frequently present with poor oral intake, failure to thrive, and chronic abdominal discomfort. Feeding aversion may arise from esophageal irritation or from a fear of food impaction. In severe cases, children experience recurrent vomiting or regurgitation. The prevalence of EoE in pediatric populations is rising, reflecting increased recognition and diagnostic vigilance.
Symptoms in Adults
Adults with EoE commonly report dysphagia to solids, intermittent food impaction, and a sensation of a tight esophageal lumen. Some patients also experience chest discomfort or post‑prandial reflux‑like symptoms that do not respond to proton pump inhibitors. Long‑term untreated disease may lead to strictures and a reduced quality of life.
Diagnostic Evaluation
Endoscopy and Biopsy
Upper endoscopy remains the gold standard for evaluating suspected EoE. The procedure allows direct visualization of mucosal patterns and targeted biopsies from the mid‑to‑distal esophagus. Multiple biopsy samples are recommended to improve diagnostic yield, as eosinophil distribution can be patchy.
Laboratory Tests
Serologic testing for IgE antibodies against common food allergens may guide dietary management but is not definitive for EoE. Complete blood counts may reveal peripheral eosinophilia in some patients; however, normal eosinophil counts do not exclude the disease. Other laboratory investigations are employed to exclude differential diagnoses, such as tests for parasitic infections or celiac disease.
Imaging Studies
High‑resolution esophageal manometry can identify motility abnormalities that coexist with eosinophilic inflammation. Barium swallow studies may demonstrate structural changes, including strictures or narrowing, but are less sensitive than endoscopy for detecting mucosal disease.
Histopathologic Features
Histologic evaluation focuses on eosinophil counts per high‑power field, the presence of eosinophilic microabscesses, basal zone hyperplasia, and papillary elongation. Additional staining for eosinophil peroxidase or major basic protein can provide insight into eosinophil activation status. The histologic pattern supports the diagnosis and can indicate disease severity.
Management and Treatment
Dietary Interventions
Elimination diets aim to remove foods that provoke eosinophilic inflammation. The most common approach is the six‑food elimination diet, which excludes milk, eggs, soy, wheat, nuts, and seafood. Successful dietary trials often involve re‑introductions to identify specific triggers. In cases where dietary restrictions are burdensome, elemental formulas composed of free amino acids may be prescribed, though compliance can be challenging.
Pharmacologic Therapy
Topical corticosteroids delivered via swallowed viscous solutions or capsules have become a mainstay of therapy. Prednisolone or fluticasone preparations reduce eosinophil infiltration and improve symptom scores. Systemic corticosteroids are reserved for refractory or severe disease due to the risk of adverse effects. Recent studies have examined biologic agents targeting IL‑5 or IgE pathways, though their efficacy remains variable across patient cohorts.
Endoscopic Therapy
Mechanical dilation addresses esophageal strictures that impede swallowing. The procedure involves graded balloon or bougie dilation, performed under endoscopic guidance. While dilation can relieve symptoms, it does not address underlying inflammation; therefore, it is usually combined with medical or dietary therapies to prevent recurrence.
Emerging Therapies
Targeted biologic agents that block key cytokines implicated in Th2 responses are under investigation. Dupilumab, an antibody that inhibits IL‑4 receptor alpha, has shown promise in reducing esophageal eosinophil counts and improving patient‑reported outcomes. Other investigational agents focus on TSLP, eotaxin‑3, and integrin pathways, reflecting the evolving understanding of disease mechanisms.
Prognosis and Outcomes
Long‑term prognosis depends on disease control and the prevention of complications such as strictures. With effective therapy, most patients achieve symptom remission and normalization of histologic findings. However, a subset of patients develops chronic fibrosis that can limit functional improvement. Regular follow‑up with endoscopy and symptom assessment is recommended to monitor disease activity and adjust treatment accordingly.
Research and Future Directions
Genetic studies have identified susceptibility loci, including variants in the genes encoding thymic stromal lymphopoietin and filaggrin, suggesting a link between barrier dysfunction and immune dysregulation. Microbiome research explores the role of esophageal flora in disease initiation and progression, offering potential for microbiota‑based interventions. Biomarker discovery focuses on non‑invasive tests, such as stool or blood eosinophil‑derived proteins, to monitor disease activity without repeated biopsies. The integration of multi‑omic data is expected to refine patient stratification and identify novel therapeutic targets.
Epidemiology
Incidence estimates of EoE vary globally, with higher rates reported in North America and Europe compared to Asian populations. The prevalence in pediatric populations ranges from 10 to 20 per 10,000 children, while adult prevalence is estimated at 15 to 35 per 10,000 individuals. Risk factors include a family history of atopy, male sex, and concurrent allergic diseases such as allergic rhinitis, asthma, or atopic dermatitis. Temporal trends indicate an increasing number of diagnoses, reflecting improved awareness and diagnostic capabilities rather than a true rise in disease frequency.
Societal Impact and Awareness
EoE imposes significant healthcare costs due to repeated endoscopies, dietary consultations, and medication use. Quality‑of‑life assessments demonstrate considerable symptom burden, especially in children with feeding difficulties and adults experiencing food avoidance. Patient advocacy groups and professional societies have launched educational initiatives to promote early recognition and standardized care pathways. These efforts have contributed to reduced diagnostic delays and improved treatment outcomes in many regions.
See Also
- Esophageal disorders
- Allergic diseases
- Immunoglobulin E–mediated hypersensitivity
- Th2 immune response
- Biologic agents in gastroenterology
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