Eosinophil Cationic Protein Testing for Eosinophilic Esophagitis
Eosinophil cationic protein (ECP) testing is NOT a reliable predictor for diagnosing eosinophilic esophagitis and should not replace endoscopy with esophageal biopsy, which remains the only reliable diagnostic test for EoE. 1
Current Diagnostic Standard
Endoscopy with esophageal biopsy is the only reliable diagnostic test for EoE. 1 The diagnosis requires:
- ≥15 eosinophils per high-power field as the minimum threshold 1, 2
- 2-4 mucosal biopsies from both proximal and distal esophagus to maximize diagnostic yield 1
- At least 6 specimens total for optimal diagnostic accuracy 3
- Biopsies should be obtained even when the esophagus appears macroscopically normal, as 21% of children with EoE have normal-appearing esophagus on endoscopy 1, 4
Evidence on ECP as a Biomarker
While research has explored ECP as a potential non-invasive biomarker, the evidence shows significant limitations:
Serum ECP Performance
The most recent high-quality study found that serum ECP had 80% sensitivity and 92.8% specificity for diagnosing EoE with a cut-off value of 13.9 µg/mL 5. However, this single study's findings have not been incorporated into clinical guidelines, and several critical limitations exist:
- Serum ECP is not sensitive or reliable for evaluating eosinophilic inflammation in chronic conditions 1
- Circadian variation requires standardized collection times 1
- Promoter polymorphisms are major determinants of serum ECP levels, affecting baseline values 1
- Normal values vary between populations, with conflicting information on effects of smoking, atopy, and age 1
ECP for Treatment Monitoring
Research suggests serum ECP may correlate with treatment response to topical corticosteroids 6, and ECP levels correlate with food impaction and endoscopic severity (EREFS score) 5. One study found serum ECP decreased significantly after fluticasone therapy (from 15.6 to 5.5 μg/L) and correlated with histologic eosinophil counts post-treatment 6.
However, ECP measurements fail to reliably reflect treatment-related changes compared to direct eosinophil counts 1, and ECP does not predict response to corticosteroid therapy 1.
Why Guidelines Do Not Recommend ECP Testing
The consensus guidelines explicitly state that biomarkers and molecular signatures that aid in the diagnosis of EoE remain unknown 1. Despite research interest, no non-invasive biomarker has achieved sufficient validation for clinical integration 7.
The British Society of Gastroenterology (2022) does not mention ECP testing in their comprehensive diagnostic algorithm 1, and the 2011 consensus recommendations emphasize that endoscopy with biopsy remains the only reliable diagnostic test 1.
Clinical Pitfalls to Avoid
- Do not use ECP testing as a screening tool or diagnostic substitute for endoscopy 1
- Do not assume normal ECP excludes EoE, as the test lacks sufficient negative predictive value for clinical decision-making 7
- Do not delay endoscopy in symptomatic patients (dysphagia, food impaction, refractory GERD symptoms) based on ECP results 1
- Remember that 7-17% of EoE patients have macroscopically normal esophagus, making biopsy essential regardless of endoscopic appearance 1
When to Perform Endoscopy
Obtain esophageal biopsies in:
- All adults with dysphagia or food bolus obstruction, even with normal-appearing esophagus 1
- All children undergoing endoscopy for upper gastrointestinal symptoms sufficiently significant to warrant the procedure 1
- Children with typical GERD symptoms refractory to proton pump inhibitors 1
- Any patient with endoscopic signs associated with EoE (furrows, rings, white plaques, mucosal edema, fragile mucosa, narrow-caliber esophagus, strictures) 1