DISCUSSION
To date, there is no data available regarding the prevalence of FIRE in both adult and pediatric cases with EoE. All the data we have on FIRE is derived from a survey study conducted on EoE experts and adult EoE patients, along with case reports of eight adults and one pediatric patient with EoE.4,5,7 Therefore, in our own EoE series, we questioned and investigated the presence of FIRE in cases aged ≥7 years old whom we believed could express their symptoms. In pediatric cases with EoE, the majority of recurrent immediate reactions to foods are associated with PFAS, and FIRE is quite rare.
In a face to face meeting on May 7th, 2017, pediatric and adult gastroenterologists and allergists, reached a consensus to assess a new phenomenon “food-induced immediate response of the esophagus” (FIRE) from the expert’s and patient’s perspective. Later, Biedermann et al. reported a survey study in which they used two seperate questionnaries composed of 20 items for physicians and patients, to assess the presence of FIRE in adult EoE patients. In this study, the unpleasant or painful retrosternal symptoms rapidly developing and recurring with the suspected foods or beverages contact with the esophageal surface were defined as FIRE. This definition does not include well-known EoE symptoms related to solid/dry/fibrous food dysphagia and symptoms consistent with gastroesophageal reflux disease.4 The majority of EoE experts estimated the prevalence of FIRE symptoms in the EoE population between <5% and 20%. On the other hand, the estimated prevalence of FIRE by EoE patients was 39.7%.4 Additionally, the reported FIRE cases so far have not provided information on whether they conducted a screening to identify these patients and if they did, how many patients were screened.5,7 In our study, we found FIRE in only one among 78 patients (1.2%). We do not know if our sample size is sufficient to demonstrate the prevalence of FIRE, however it is at least the first screening study conducted on this issue. Certainly, in order to determine the true prevalence of FIRE in EoE which is already known a rare disease, larger number of patients may need to be screened.
The pathogenesis of FIRE is not known yet. However, it is hypothesized to be IgE mediated due to rapid onset of symptoms after food exposure and association with allergic comorbidities in adult cases.4,5 Skin prick test (SPT) positivity with suspected foods was present in the single pediatric case and in half of the adult cases with FIRE.5,7 On the other hand diagnostic criteria of FIRE has not been clarified yet. Therefore, it is not clear whether a positive reaction to the suspected food in SPT is absolutely necessary for diagnosis. In this respect, esophageal prick tests in addition to SPT with suspected foods may provide input for immediate esophageal mucosal response both for pathogenesis and diagnosis of FIRE.9 It is also suggested that a chemical irritation of the inflamed esophageal mucosa may cause symptoms related to FIRE.4
In adult patients with EoE, another well-defined IgE-mediated reaction triggered by food is PFAS.10-12 However, data about the comorbidity of PFAS in children with EoE is limited.10,13 PFAS has been studied in two retrospective case series of pediatric EoE, with one reporting PFAS in 7 out of 137 patients (5.1%), while the other series did not report PFAS in any of the 372 cases (0%).10,13 Although it is not a primary aim of the study, we found that PFAS in children with EoE is not rare (15.3%) as previously reported.10,13 In addition, all of our patients with PFAS and one case with FIRE had comorbid AR. This was a similar finding to adult case series with FIRE.5 Therefore, we also believe that FIRE should be specifically questioned in EoE cases, particularly those with identified AR and/or PFAS.5 Despite their rapid onset and frequent co-existence, it is important to differentiate between PFAS and FIRE due to the completely different nature of their symptoms. On the other hand, FIRE symptoms should also be differentiated from well-known solid food dysphagia seen in EoE cases. Generally, EoE patients are more familiar with dysphagia related to solid foods, and they alleviate these symptoms by drinking water, jumping, chest pounding, inducing vomiting, or developing adaptive eating behaviors.14 These strategies except avoidance do not provide relief for FIRE symptoms and this can be used as a distinguishing question.
The most common food triggers for FIRE are fresh vegetables and fruits like PFAS. Differently, liquids such as wine, beer, and vinegar were defined by both patients and physicians and determined in two of eight adult cases as FIRE triggering foods.4,5 Because our patient with FIRE was able to consume fresh cucumber without any issues but experiencing symptoms triggered by pickled cucumber on at least three separate occasions, we hypothesized that vinegar could be the triggering food/beverage.
The sample size may be a limitation of the study. Although SPT positivity is not an obligation to diagnose FIRE according to previously reported adult cases, it would be better if our patient consented on the test. On the other hand, being the first screening study of FIRE in children with EoE in a referral center is the strength of our study.
In conclusion, although we can not comment on true prevalence of FIRE, we believe that it is not common as PFAS but deserves to be a routine part of EoE history as other allergic comorbidities especially in the presence of concurrent AR and/or PFAS. Future studies should concentrate on understanding the pathogenesis of FIRE and identifying diagnostic criteria.