# Shedding Light on FIRE Syndrome: An Overview of a Novel Condition in Eosinophilic Esophagitis
## 1 Introduction  
Eosinophilic esophagitis (EoE) is a chronic, immune-driven esophageal condition associated with type 2 inflammation and characterized by esophageal eosinophil. It is frequently associated with other type 2 atopic conditions such as atopic dermatitis, IgE-mediated food allergy, and rhinitis, and it can possibly be interpreted as a late-stage manifestation of the allergic march [1].  
EoE is characterized by esophageal motility dysfunction symptoms associated with eosinophil infiltrate of the esophageal mucosa in response to food or environmental allergens [2]. Its diagnosis consists of an eosinophil count of >15 eosinophils per high-power field (HPF) or 60 eosinophils/mm\({}^{2}\) in esophageal biopsies, after excluding other common causes of esophageal eosinophil, such as gastroesophageal reflux disease (GERD), infections, eosinophilic gastrointestinal diseases (EGIDs), drug hypersensitivity reactions, connective tissue diseases, and hypereosinophilic syndrome [2].  
Since its initial reports in the literature, dating back to the late 1980s, EoE has been a subject of significant interest, positioned at the intersection of several medical specialties [3; 4]. In recent years, there has been a growing focus on this condition, showing a marked increase in its recognition, with EoE being the leading cause of dysphagia in children and adults [5]. The pooled incidence estimated in a recent meta-analysis was 6.6 per 100,000 per year in children and 7.7 per 100,000 per year in adults, alongside a global prevalence of 34.4 per 100,000 individuals [6]. The increased awareness of EoE with a higher frequency of esophageal biopsies during esophagogastroudoenoscopy may explain this observed trend. However, similar to other atopic conditions, evidence suggests that its incidence is genuinely increasing, independent of improved diagnostic recognition [7; 8].  
Recognition and diagnosis of EoE occur in individuals of all ages, including both adults and children. Its clinical presentation is defined by esophageal dysfunction, with solid food dysphagia and food impaction being the hallmark symptoms of this disease. The phenotypic expression of EoE seems to be highly age-dependent, considering that non-specific symptoms such as abdominal pain, vomiting, regurgitation, or feeding difficulties are more common in children [8; 9]. A recent systematic review reported that 13% to 75.3% of EoE patients suffered from feeding difficulties [10]. These patients developed modified eating behaviors, for instance, frequently drinking during meals, eating in small portions, or chewing excessively, all of which contributed to delayed diagnosis [8; 11; 12]. The mean diagnostic delay in patients with EoE has been found to be around 4 years, with longstanding inflammation leading to complications such as esophageal fibrosis with strictures. There is evidence suggesting that each additional year of untreated EoE increases the risk of stricture by 9% [13; 14; 15].  
Recent publications describe that a subset of EoE patients experience an immediate hypersensitivity-like response upon exposure to different foods or beverages, which appears to be distinct from the chronic delayed Th2-driven symptoms typically seen in EoE [16]. This novel entity has been characterized as Food-Induced Immediate Response of the Esophagus (FIRE) syndrome. FIRE syndrome presents with acute retrosteral pain, food impaction leading to a choking sensation, and dysphagia, which is different from classical dysphagia seen in EoE [16]. Unlike classic EoE, where symptoms worsen gradually over time, FIRE syndrome involves a rapid-onset, reproducible esophageal reaction upon exposure to different foods or beverages, raising important questions about its pathophysiology and optimal management [16; 17]. Given the lack of standardized diagnostic criteria and the low recognition of this syndrome in EoE population, further research is needed in order to identify it, understand the mechanisms that drive its clinical presentation, and develop tailored therapeutic approaches.