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.