Shedding Light on FIRE Syndrome: An Overview of a Novel Condition in Eosinophilic Esophagitis

Food-Induced Immediate Response of the Esophagus (FIRE) is a newly described syndrome observed in eosinophilic esophagitis (EoE) patients. It is defined by an immediate hypersensitivity reaction of the esophagus that occurs when specific foods and beverages interface with esophageal mucosa. The available data regarding this topic is scarce. Therefore, we aimed to review relevant publications in order to better characterize the main aspects of this syndrome and hypothesize about potential mechanisms underlying FIRE syndrome and possible future therapeutic approaches. We searched PubMed, Embase, and Web of Science databases for relevant articles published before February 1st, 2025. The results were narrowed down to four articles describing a total of 105 cases of FIRE syndrome. These patients had a distinct clinical presentation, characterized by retrosternal discomfort or pain, differentiating it from solid food dysphagia or pollen-food allergy syndrome (PFAS). Currently, diagnosis is based on clinical presentation, with no diagnostic tests or biomarkers available. Emerging evidence suggests that IgE-mediated hypersensitivity, mast cells, and neuroimmune interactions may play a central role in the pathogenesis of FIRE syndrome. The therapeutic approaches remain speculative, with trigger avoidance being the main option. This article brings to the forefront the need for continued research to address current knowledge gaps regarding FIRE syndrome, which is important for optimizing patient management.