Non-endoscopic Biomarkers and Sampling for Diagnosis and Monitoring of Adult Eosinophilic Esophagitis: A Systematic Review and Pooled Analysis

Eosinophilic esophagitis (EoE) typically requires endoscopic biopsy for diagnosis and disease monitoring, but less invasive tools may offer clinical utility. This systematic review evaluated the diagnostic performance and treatment responsiveness of non-endoscopic biomarkers and sampling techniques in adult EoE. Sixteen studies met the inclusion criteria. Diagnostic biomarkers such as eosinophil-derived neurotoxin (EDN), major basic protein (MBP), and eosinophilic cationic protein (ECP) showed inconsistent performance across studies. Absolute eosinophil count (AEC) was significantly elevated in active EoE, though reported in only one study. Minimally invasive sampling tools, including cytosponge and liquid-based cytology (LBC), demonstrated moderate sensitivity (70-75%) and specificity (56-86%) for the diagnosis of EoE. For monitoring treatment response, pooled analysis revealed significant reductions in AEC, ECP, and EDN following therapy, while MBP, eotaxin-3, IL-5, and IL-13 showed no meaningful change. Risk of bias was moderate, largely due to variability in biomarker thresholds and lack of treatment stratification. These findings suggest non-endoscopic tools may complement standard histologic evaluation but require prospective validation in larger cohorts before routine clinical use.