Introduction
Eosinophilic esophagitis, abbreviated EoE, is a chronic immune-mediated inflammatory disorder of the esophagus. It is characterized by an eosinophil-predominant infiltrate in esophageal mucosa and is associated with clinical symptoms related to esophageal dysfunction. The condition has been increasingly recognized over the past three decades, with a corresponding rise in both diagnosis and research. EoE can affect individuals of all ages, but the highest prevalence is observed in young adults, especially males, and in children presenting with feeding or swallowing difficulties. Although it was once considered a rare disease, contemporary epidemiologic data suggest a prevalence that may reach 1–2 per 1,000 individuals in certain populations.
The disease course can vary widely: some patients experience intermittent flare‑ups, while others progress to strictures, rings, or food impaction. The pathogenesis of EoE is multifactorial, involving genetic predisposition, environmental exposures, allergic sensitization, and aberrant immune responses. Management strategies focus on controlling inflammation and relieving symptoms, using dietary interventions, pharmacologic agents, or endoscopic procedures. Long‑term treatment is typically required, and ongoing research seeks to refine therapeutic approaches and to elucidate underlying mechanisms.
Terminology and Etymology
The term “eosinophilic esophagitis” was first introduced in the early 1990s when a distinct group of patients with esophageal eosinophilia was described. The suffix “‑itis” denotes inflammation, while “esophag‑” refers to the esophagus, and “eosinophilic” indicates the predominant presence of eosinophils, a type of white blood cell. The abbreviation EoE is widely used in clinical, research, and educational contexts.
Historical descriptions of similar conditions date back to the early 20th century, but they were often classified under more general terms such as “gastro‑esophageal reflux disease” or “esophageal allergic disease.” The recognition of a separate eosinophilic phenotype has clarified diagnostic criteria and facilitated targeted management strategies.
Clinical Presentation
Symptoms
Patients with EoE commonly present with symptoms related to esophageal motility and structural changes. In children, feeding aversion, vomiting, abdominal pain, and failure to thrive are frequent manifestations. Adults more often report dysphagia, food impaction, chest discomfort, or a sensation of food sticking in the chest. The symptom spectrum can overlap with other esophageal disorders, necessitating careful evaluation.
Age of Onset
Onset typically occurs in childhood or early adulthood, though cases have been reported across the lifespan. The mean age at diagnosis is around 30 years, with a notable peak in the second decade for pediatric patients. Male predominance is observed, with a male-to-female ratio ranging from 2:1 to 4:1 in several studies.
Clinical Features
- Early symptom of food impaction or “stuck” sensation.
- Progression to rings, strictures, or eosinophilic infiltrates on endoscopy.
- Potential extra‑esophageal manifestations such as allergic rhinitis, asthma, or atopic dermatitis.
- Variable severity: some individuals remain asymptomatic with incidental findings on endoscopy, while others experience disabling dysphagia.
Pathophysiology
Immune Mechanisms
EoE is considered an allergic disease involving a Th2‑biased immune response. Key cytokines include interleukin‑5 (IL‑5) and interleukin‑13 (IL‑13), which promote eosinophil recruitment, activation, and survival. Epithelial barrier dysfunction, driven by down‑regulation of tight junction proteins, allows increased antigen penetration, further amplifying immune activation.
Eosinophil Migration and Activation
Upon recruitment, eosinophils infiltrate the esophageal mucosa and release cytotoxic granule proteins such as major basic protein, eosinophil peroxidase, and eosinophil cationic protein. These mediators contribute to tissue damage, fibrosis, and remodeling, which can manifest clinically as strictures or rings.
Genetic Factors
Familial clustering suggests a hereditary component. Genome-wide association studies have identified susceptibility loci, notably on chromosome 5q22 (encoding thymic stromal lymphopoietin) and 2p23 (encoding filaggrin). Polymorphisms in these genes may influence epithelial barrier integrity and immune responses.
Environmental Factors
Allergens commonly implicated include aeroallergens such as pollen, dust mites, and animal dander, as well as food allergens including dairy, wheat, soy, and eggs. Early life exposure, diet, and microbial colonization patterns are being explored for their roles in disease onset and progression.
Diagnostic Criteria
Endoscopic Assessment
During upper endoscopy, characteristic findings may include longitudinal furrows, rings (“trachealization”), white exudates, edema, and strictures. These features, while suggestive, are not definitive; histologic confirmation remains essential.
Biopsy and Histology
Multiple esophageal biopsies (typically 4–6 from proximal, mid, and distal esophagus) are recommended. A threshold of ≥15 eosinophils per high-power field (HPF) in any specimen is the most widely accepted criterion for EoE. Additional histologic features such as basal zone hyperplasia, papillary elongation, and lamina propria edema support the diagnosis.
Exclusion of Other Causes
Other potential causes of esophageal eosinophilia include gastro‑esophageal reflux disease, infections (e.g., viral or parasitic), drug reactions, eosinophilic granulomatosis with polyangiitis, and systemic disorders such as eosinophilic pneumonia. Appropriate testing for reflux (pH monitoring), infections, and autoimmune markers is often performed to exclude these conditions.
Diagnostic Workflow
- Clinical evaluation and symptom scoring.
- Upper endoscopy with targeted biopsies.
- Histologic analysis of eosinophil counts and architectural changes.
- Assessment for reflux, infection, and systemic disease.
- Confirmation of diagnosis based on established criteria.
Management and Treatment
Dietary Therapy
Allergen avoidance remains a cornerstone for many patients. Common dietary strategies include the six‑food elimination diet (eliminating milk, wheat, soy, eggs, peanuts/tree nuts, and seafood), elemental diets using amino acid formulas, and customized elimination based on allergy testing.
Pharmacologic Therapy
Topical swallowed corticosteroids, such as fluticasone propionate or budesonide, are first‑line treatments. The formulation is typically a slurry or suspension that patients swallow without swallowing the entire dose to limit systemic absorption. Long‑term therapy can achieve remission in a substantial proportion of patients.
Proton pump inhibitors (PPIs) are used both to treat concomitant reflux and, in some cases, as a diagnostic therapeutic trial to exclude PPI-responsive esophageal eosinophilia.
Endoscopic Therapy
In patients with luminal narrowing, dilation is performed to relieve dysphagia. Endoscopic injection of corticosteroids or balloon dilation may be employed for refractory strictures. However, repeated procedures carry risks of perforation and restenosis.
Emerging Therapies
Biologic agents targeting Th2 cytokines, such as anti‑IL‑5 antibodies (mepolizumab, reslizumab) and anti‑IL‑13 antibodies (lebrikizumab), have shown promise in controlled trials. Small‑molecule inhibitors of the eotaxin‑CCR3 axis and the Janus kinase pathway are also under investigation.
Prognosis and Outcomes
Natural History
Without treatment, EoE can lead to progressive fibrosis and stricturing, increasing the risk of dysphagia and food impaction. Symptom severity may fluctuate, with periods of remission and exacerbation. Longitudinal studies indicate that early intervention may reduce progression to irreversible strictures.
Remission and Relapse
Remission rates vary depending on the treatment modality. Topical steroids have demonstrated sustained remission in up to 50% of patients after 6–12 months of therapy. Dietary therapy may produce similar outcomes but requires stringent adherence. Relapse frequently occurs upon discontinuation of treatment, necessitating ongoing monitoring.
Complications
- Stricture formation leading to progressive dysphagia.
- Food impaction requiring emergency endoscopy.
- Potential systemic side effects of long‑term steroid use, such as adrenal suppression or osteoporosis.
- Psychological burden due to chronic disease management.
Epidemiology
Incidence and Prevalence
Incidence estimates range from 0.2 to 4.9 cases per 100,000 person‑years, depending on geographic region and diagnostic criteria. Prevalence figures vary widely, with reported values from 0.1% to 1% in certain cohorts. The apparent increase over recent decades may reflect heightened awareness, improved diagnostic protocols, and better reporting.
Demographics
Men are affected more frequently than women, with a male predominance that may reflect both biological and environmental exposures. Children with atopic dermatitis or asthma are at higher risk, supporting the link between atopy and EoE. Ethnic variations have been noted, with higher rates reported among Caucasians compared to other groups, though data are limited.
Geographic Variation
Urban centers and developed countries exhibit higher reported prevalence, likely due to greater diagnostic resources and surveillance. Rural or resource-limited settings may underreport EoE due to limited endoscopic availability. Environmental factors, such as dietary patterns and allergen exposure, are hypothesized to contribute to regional differences.
Research and Future Directions
Clinical Trials
Large randomized controlled trials are underway to assess the efficacy of biologic agents and novel therapeutic approaches. Phase III studies of anti‑IL‑5 and anti‑IL‑13 antibodies aim to define optimal dosing, patient selection, and long‑term safety.
Biomarkers
Non‑invasive biomarkers, such as fecal eosinophil‑derived neurotoxin or blood eosinophil counts, are being evaluated for diagnostic and monitoring purposes. The development of reliable biomarkers could reduce the need for repeated endoscopy.
Personalized Medicine
Integrating genomic, proteomic, and immunologic data may allow for individualized treatment plans, targeting specific pathways active in a given patient. Precision medicine approaches may improve outcomes and reduce treatment burden.
Public Health Initiatives
Educational programs for clinicians and patients emphasize early recognition, referral pathways, and multidisciplinary care models. Efforts to standardize diagnostic criteria and reporting practices aim to enhance epidemiologic accuracy.
Societal and Psychological Impact
Quality of Life
Patients with EoE often report reduced health‑related quality of life, citing limitations in diet, social eating, and sleep disturbance. Symptom burden correlates with emotional distress and anxiety. Validated questionnaires such as the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) and the Eosinophilic Esophagitis Activity Index (EoE‑AI) are used to quantify impact.
Psychosocial Aspects
Children may experience bullying or social isolation due to dietary restrictions. Adults report feelings of frustration and helplessness from chronic disease management. Psychological support, counseling, and peer support groups are recommended components of comprehensive care.
Economic Burden
The cost of EoE management includes endoscopic procedures, medication, specialized diets, and indirect costs such as missed work or school days. Health‑economic analyses suggest that effective disease control can reduce overall expenditures by limiting complications and hospitalizations.
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