Eosinophilic Esophagitis without Eosinophils: Do You Want to Mock Me?

Background: Eosinophils and eosinophil infiltration are the hallmark for the diagnosis of eosinophilic esophagitis (EoE), which represents the most common cause of solid food dysphagia in young adults. However, the role of eosinophils in the pathogenesis of EoE has been increasingly questioned. Summary: It is now well accepted that EoE is a Th2-mediated disorder with a myriad of inflammatory processes being involved rather than a single cell disease. In recent years, several nuances of EoE, so-called EoE variants, have been described, among which are EoE-like esophagitis, nonspecific esophagitis, lymphocytic esophagitis, and potentially also mast-cell esophagitis. These variants appear to have distinct molecular fingerprints sharing pronounced traits of EoE. Of note, there is a considerable flux between the variants (with frequent transitions) and eventual progression to EoE over time. Thus, EoE variants and EoE appear to be a spectrum disorder, where EoE only represents the most extreme phenotype. Key Messages: This review summarizes current knowledge about these different variants and discusses future directions and open questions.