Eosinophilic esophagitis - more than eosinophils?

Eosinophilic esophagitis (EoE) is a chronic, type 2 inflammatory disease with a rapidly rising incidence and is a leading cause of solid-food dysphagia in young adults. While diagnosis has traditionally relied on esophageal eosinophilia, the central role of eosinophils in driving symptoms and disease activity has been increasingly questioned, as several non or low-eosinophilic EoE variants have recently been characterized. This review summarizes the current understanding of these emerging entities and their position within the EoE spectrum.

Current concepts support EoE as a Th2-mediated, multicellular disorder driven by genetic susceptibility, epithelial barrier dysfunction, and allergen-induced immune responses. Three EoE variants (EoE-like esophagitis, lymphocytic esophagitis, and nonspecific esophagitis) present with EoE-typical symptoms but fall below the diagnostic eosinophil threshold. Molecular and longitudinal data reveal distinct yet overlapping inflammatory signatures and demonstrate dynamic transitions between phenotypes, including progression to classical EoE in a subset of patients.

EoE variants demonstrate that clinically meaningful esophageal inflammation and structural remodeling can occur in the absence of significant tissue eosinophilia. Recognition of these entities has direct implications for biopsy strategy, histologic assessment beyond peak eosinophil counts, structured longitudinal monitoring and therapy to prevent fibrostenotic complications.