Compartment-based biomarker integration for clinical monitoring in eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease in which symptoms correlate imperfectly with histologic and structural activity, necessitating repeated endoscopy for diagnosis and monitoring. As therapeutic options expand, including biologic agents, there is an increasing need for biomarkers that can inform clinical decision-making and support treat-to-target strategies. This narrative review synthesizes current evidence on tissue-based, circulating, and minimally invasive biomarkers in EoE and proposes a compartment-based clinical hierarchy to contextualize their performance in routine practice. While type 2 cytokine pathways define disease biology, their systemic measurement demonstrates limited diagnostic and monitoring value. By contrast, tissue transcriptomic signatures and esophageal-proximal assessments-particularly eotaxin-3 and eosinophil-derived granule proteins-show stronger correlation with mucosal inflammation and therapeutic response. Structural and epithelial markers further highlight that histologic remission does not necessarily equate to restoration of mucosal integrity. Across domains, biomarker utility follows a consistent gradient, with tissue and luminal assessments most closely reflecting active disease, whereas circulating markers serve adjunctive roles. Histologic scoring systems remain the reference standard; however, multimodal integration of molecular and minimally invasive tools may enable remodeling-aware monitoring and reduce endoscopy burden in selected clinical contexts. Prospective validation within clearly defined management algorithms is required before routine implementation.