# Shedding Light on FIRE Syndrome: An Overview of a Novel Condition in Eosinophilic Esophagitis
## 2 Reported Cases of FIRE Syndrome: Insights from the Literature
### The Main Characteristics of Reported Cases  
The majority of current understanding regarding FIRE syndrome originates from the researchers who first described this phenomenon. In their study, [PERSON] et al. [16] used a questionnaire-based survey among EoE experts and patients to better characterize FIRE syndrome patients' profiles. It was estimated that symptoms consistent with FIRE syndrome occur in less than 5% to up to 20% for the adult EoE population. In contrast, patient-reported symptoms suggest a possible higher prevalence of almost 40% [16]. These estimates are based on subjective assessments rather than epidemiologic data, and should be interpreted as preliminary insights. Importantly, all FIRE syndrome cases have so far been self-reported by patients, and no data are currently available concerning the use of oral food challenges to formally assess this syndrome [16; 17; 18; 19]. As evidence is still emerging, available epidemiological data remain limited to small cohorts. For instance, [PERSON] et al. 's  
Figure 1: Overview of article identification and selection process for this review. study reported a prevalence of 1.2% in their cohort of pediatric patients, suggesting a potential age-related difference [19]. Given the small number of patients being surveyed and the observational nature of these case series, it remains unclear whether this difference is truly age-dependent. The following section aims to summarize key findings from the reported cases, highlighting the defining features observed in these patients. A total of 105 cases have been reported so far across the four articles included in the research [16; 17; 18; 19]. Their key characteristics are presented in Table 1.  
Of the total 105 patients, 103 were adults reported in two studies: 95 patients with a mean age of 46 years in the first study, and 8 patients with a mean age of 35 years in the second study [16; 17]. Furthermore, there were two cases reported in the pediatric EoE population of 9 and 16 years of age, respectively [18; 19]. The occurrence of FIRE symptoms appears to be linked to an earlier age of EoE diagnosis. Additionally, this syndrome seems to be more common among male patients with a history of food bolus impactions necessitating endoscopic intervention [16]. Regarding the correlation with EoE activity, FIRE syndrome symptoms appear to develop at variable stages in the course of the disease and may not be directly linked to active eosinophilic inflammation. In [PERSON] et al. 's patient cohort, only 28.4% reported having FIRE syndrome symptoms only in relation to active EoE, while almost 39% described this phenomenon independently of EoE activity [16]. Examining the temporal association between the initial FIRE syndrome manifestations and EoE diagnosis, data from the same study showed that in 31.6% of cases FIRE syndrome symptoms preceded EoE's clinical expression, in 24.2% they appeared after EoE onset, and only 15.8% of FIRE syndrome patients reported symptoms concomitant with EoE. Notably, 24.2% were unable to clearly define the timeline [16]. These observations suggest a heterogenous pattern, with a potential trend toward FIRE syndrome symptoms occurring early in the disease course, in some cases preceding EoE diagnosis. This temporal trend warrants further investigation as there are still insufficient data to establish FIRE syndrome as a predictive marker for EoE. If validated, FIRE syndrome could serve as a potential clinical red flag, prompting earlier diagnostic work-up for EoE. As for its persistence, symptoms remitted in 12.7% of patients after a median period of 4 years, allowing for speculation that FIRE syndrome may not be a permanent condition [16]. Additional data are necessary to make a definite conclusion in this regard. Another important aspect to consider is the broad atopic profile of FIRE syndrome patients. EoE is strongly linked to other atopic conditions [20].