What is the most accurate way to diagnose eosinophilic esophagitis (EoE)?

Diagnosis of Eosinophilic Esophagitis

The most accurate way to diagnose eosinophilic esophagitis is endoscopy with esophageal biopsies showing ≥15 eosinophils per 0.3 mm² (high-power field) in the context of symptoms of esophageal dysfunction, after excluding other causes of esophageal eosinophilia. 1

Essential Diagnostic Components

EoE is a clinicopathological diagnosis requiring integration of three elements 1, 2:

• Clinical symptoms of esophageal dysfunction (dysphagia, food impaction, chest pain, or heartburn) 1, 2
• Histologic threshold of ≥15 eosinophils per 0.3 mm² on esophageal biopsy 1
• Exclusion of alternative causes of esophageal eosinophilia (GERD, infections, hypereosinophilic syndrome, drug hypersensitivity, Crohn's disease, connective tissue disorders) 1, 2

Optimal Biopsy Protocol

Obtain at least 6 biopsies from a minimum of 2 different esophageal sites (proximal and distal, or distal and middle) to maximize diagnostic yield. 1

Why Multiple Biopsies Matter

The eosinophilic infiltrate in EoE is patchy in distribution, making single-site sampling unreliable 1, 3:

• 2 biopsies: 84% sensitivity 4, 2
• 3 biopsies: 97% sensitivity 4, 2
• 6 biopsies: 97-100% diagnostic accuracy 1

Biopsy Technique

• Combine targeted biopsies from visible mucosal abnormalities (white spots, furrows, rings) with non-targeted biopsies from normal-appearing areas 1
• Include both distal and middle esophagus as standard protocol, since isolated mid-esophageal disease occurs in up to 10% of cases 3
• Always biopsy even when mucosa appears normal, as approximately 10% of histologically confirmed EoE patients have normal endoscopic appearance 4, 2

Critical Pitfalls to Avoid

Endoscopic Appearance Is Insufficient

Do not rely on endoscopic findings alone for diagnosis. 4, 2 While characteristic features (rings, furrows, white exudates, edema, strictures, narrow-caliber esophagus) suggest EoE, only 38% of patients with suggestive endoscopic features have histologic confirmation, and 9.8% with normal-appearing esophagus have histologic disease 4, 2.

PPI Therapy Considerations

A PPI trial is NOT required for diagnosis in the current consensus. 1 However, you must consider concomitant therapy when interpreting results 1:

• Patients on PPI therapy with normal biopsies cannot be definitively ruled out for EoE, as their off-PPI status is unknown 1, 2
• For optimal diagnostic accuracy, consider withdrawing PPIs for at least 3 weeks prior to endoscopy if clinically appropriate 1
• EoE that responds to PPI is considered the same disease as PPI-refractory EoE 1
• GERD and EoE can coexist in the same patient 1

Peripheral Blood Testing Is Not Diagnostic

Do not use peripheral eosinophil counts for diagnosis. 4 Only 10-50% of EoE patients show modest elevations in blood eosinophils, and this finding is non-specific for allergic conditions 4. EoE is a localized mucosal immune reaction (IgG4-mediated), not a systemic eosinophilic disorder 4.

Histologic Reporting Standards

Pathologists should report 1:

• Peak eosinophil density per 0.3 mm² (standardized high-power field area)
• Additional histologic features supporting EoE diagnosis: basal cell hyperplasia, edema (spongiosis), eosinophil microabscesses, eosinophil layering, eosinophil degranulation, and subepithelial sclerosis 1

When to Obtain Additional Biopsies

Obtain gastric and duodenal biopsies 1, 2:

• Routinely in pediatric patients 1
• In adults when symptoms, endoscopic findings, or high suspicion suggests other eosinophilic gastrointestinal disorders 1, 2

Consider repeat endoscopy if initial histology was non-diagnostic but high clinical suspicion persists with suggestive endoscopic features or typical symptoms 1.