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\begin{document}

\title{FOOD-INDUCED IMMEDIATE RESPONSE OF THE ESOPHAGUS (FIRE) IN PEDIATRIC
EOSINOPHILIC ESOPHAGITIS}



\author[1]{Gizem Koken}%
\author[1]{Hacer Ertoy Karagol}%
\author[1]{Sinem Polat Terece}%
\author[1]{Zeynep Cavdar}%
\author[1]{Kenan Cetin}%
\author[2]{Odul Gurkan}%
\author[2]{Sinan Sari}%
\author[2]{Buket Dalgic}%
\author[1]{Arzu Bakirtas}%
\affil[1]{Gazi University Faculty of Medicine}%
\affil[2]{Gazi University Pediatric Eosinophilic Gastrointestinal Diseases Working Group}%


\vspace{-1em}



  
  \date{May 19, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
\emph{Background:} Food-induced immediate response of the esophagus
(FIRE) is a new phenomenon that has been described in eosinophilic
esophagitis (EoE) patients. It is suspected when unpleasant symptoms
occur suddenly on contact of the triggering food with the esophageal
surface and recur with repeated exposures. It can often be mistaken for
pollen-food allergy syndrome (PFAS) and solid food dysphagia. Data on
FIRE is limited to one survey study and case reports, and there are no
screening studies conducted on either adults or children with EoE. In
this study, we aimed to screen children aged [?]7 years old with EoE for
FIRE. \emph{Methods:} Demographic data were collected from medical
records. A questionnaire about FIRE was applied to all participants.
Skin prick tests (SPTs) were done on suspected patients to identify the
triggering foods. FIRE is defined as suitable clinical symptoms with
suspected food allergen exposure. \emph{Results:} Seventy-eight patients
(74.4\% male, median age: 13.5 years) were included. Unpleasant and
recurrent symptoms distinct from dysphagia with specific foods were
reported in \%16.7 of the patients, all of whom had concomitant allergic
rhinitis (AR). The symptoms described by almost all patients were
oropharyngeal itching and tingling (PFAS: 15.3\%) excluding only one
patient reporting retrosternal narrowing and pressure after specific
food consumption (FIRE: 1.2\%). \emph{Conclusions:} Although definitive
conclusions regarding the true prevalence of FIRE cannot be made, it
does not seem to be common as PFAS. However, it deserves questioning
particularly in the presence of concurrent AR and/or PFAS in children
with EoE.%
\end{abstract}%



\sloppy


\textbf{FOOD-INDUCED IMMEDIATE RESPONSE OF THE ESOPHAGUS (FIRE)}

\textbf{IN PEDIATRIC EOSINOPHILIC ESOPHAGITIS}

\textbf{SHORT TITLE: FIRE IN PEDIATRIC EOSINOPHILIC ESOPHAGITIS}

Gizem Koken,\textsuperscript{1,3} Hacer Ilbilge Ertoy
Karagol,\textsuperscript{1,3} Sinem Polat
Terece,\textsuperscript{1,3}Zeynep Cavdar,\textsuperscript{1,3} Kenan
Cetin,\textsuperscript{1,3}Odul Egritas Gurkan,\textsuperscript{2,3}
Sinan Sari,\textsuperscript{2,3} Buket Dalgic,\textsuperscript{2,3} Arzu
Bakirtas,\textsuperscript{1,3}

\textsuperscript{1}Department of Pediatric Allergy, Gazi University
Faculty of Medicine, Ankara, T\selectlanguage{ngerman}ürkiye

\textsuperscript{2}Department of Pediatric Gastroenterology, Gazi
University Faculty of Medicine, Ankara, Türkiye

\textsuperscript{3}Gazi University Pediatric Eosinophilic
Gastrointestinal Diseases Working Group

\textbf{ACKNOWLEDGEMENTS}

We acknowledge all patients and their parents participating in this
study.

\textbf{ABSTRACT}

Background: Food-induced immediate response of the esophagus (FIRE) is a
new phenomenon that has been described in eosinophilic esophagitis (EoE)
patients. It is suspected when unpleasant symptoms occur suddenly on
contact of the triggering food with the esophageal surface and recur
with repeated exposures. It can often be mistaken for pollen-food
allergy syndrome (PFAS) and solid food dysphagia. Data on FIRE is
limited to one survey study and case reports, and there are no screening
studies conducted on either adults or children with EoE. In this study,
we aimed to screen children aged \selectlanguage{english}[?]7 years old with EoE for FIRE.

Methods: Demographic data were collected from medical records. A
questionnaire about FIRE was applied to all participants. Skin prick
tests (SPTs) were done on suspected patients to identify the triggering
foods. FIRE is defined as suitable clinical symptoms with suspected food
allergen exposure.

Results: Seventy-eight patients (74.4\% male, median age: 13.5 years)
were included. Unpleasant and recurrent symptoms distinct from dysphagia
with specific foods were reported in \%16.7 of the patients, all of whom
had concomitant allergic rhinitis (AR). The symptoms described by almost
all patients were oropharyngeal itching and tingling (PFAS: 15.3\%)
excluding only one patient reporting retrosternal narrowing and pressure
after specific food consumption (FIRE: 1.2\%).

Conclusions: Although definitive conclusions regarding the true
prevalence of FIRE cannot be made, it does not seem to be common as
PFAS. However, it deserves questioning particularly in the presence of
concurrent AR and/or PFAS in children with EoE.

\textbf{KEY WORDS}

Eosinophilic esophagitis (EoE), food-induced immediate response of the
esophagus (FIRE), pediatrics, pollen-food allergy syndrome (PFAS)

\textbf{INTRODUCTION}

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease,
characterized by eosinophilic inflammation of the esophagus and clinical
symptoms associated with esophageal dysfunction.\textsuperscript{1,2} It
is diagnosed by histopathological evaluation as \selectlanguage{english}[?]15 eosinophils per high
powered field (hpf) in the presence of recurrent or persistent
gastrointestinal symptoms and excluding secondary
causes.\textsuperscript{1,3} The main gastrointestinal symptoms are
solid food dysphagia and food impaction in adolescents and
adults.\textsuperscript{1} On the other hand, children may present
different symptoms such as abdominal pain, nausea, vomiting, food
refusal.\textsuperscript{2,3}

Recently, a new phenomenon has been described in adult EoE patients
called food-induced immediate response of the esophagus
(FIRE)\textsuperscript{4}. It is suspected in the presence of unpleasant
even painful symptoms that occur suddenly on contact of the triggering
food with the esophageal surface and recur with repeated exposures to
the same food.\textsuperscript{4} These symptoms are unrelated to solid
food dysphagia and food impaction, which are well described by patients
with EoE. In contrast in case of FIRE, patients usually complain about
narrowing, choking and pressure in the esophagus and/or retrosternal
region immediately after ingestion of the triggering
food.\textsuperscript{4,5}

However, FIRE can often be mistaken for and coexist with pollen-food
allergy syndrome (PFAS), so it is important to differentiate between the
two.\textsuperscript{4,5} Similar to PFAS, FIRE is often triggered by
fresh fruits and vegetables and develops
rapidly.\textsuperscript{4}Unlike PFAS, symptoms such as itching,
tingling, and numbness which typically occur in the oropharyngeal
cavity, are not observed in FIRE.\textsuperscript{4,6}

So far, FIRE has been reported in eight adult
cases\textsuperscript{5}and in only one pediatric
case\textsuperscript{7} and first described in a survey based study on
EoE experts and patients.\textsuperscript{4} In this study, for the
first time, we screened children with EoE aged \selectlanguage{english}[?]7 years old for FIRE.

\textbf{METHODS}

\textbf{Design of the study and participants}

The study was conducted at a single referral center for pediatric EoE
patients in Turkiye, Children \selectlanguage{english}[?]7 years old with a diagnosis of EoE were
included. The demographics of the participants were taken from medical
records. A questionnaire consisting of 14 questions on the symptoms and
characteristics of FIRE was applied by the same investigator (GK) to the
participants or to their parents when appropriate (Supplement 1). The
study was approved by the instutional Ethics Committee (2023-731)
Informed written consent and/or assent were obtained according to the
participant's age.

\textbf{Definitions}

Eosinophilic esophagitis (EoE): The diagnosis of EoE was based on
symptoms associated with esophageal dysfunction and the presence of
intraepithelial eosinophils in the esophagus (\selectlanguage{english}[?]15 eosinophils/hpf),
after excluding secondary causes of esophageal
eosinophilia.\textsuperscript{1,3}

Food-induced immediate response of the esophagus (FIRE) : FIRE is
defined as reproducible unpleasant symptoms occuring immediately after
intake of certain foods, unrelated to the well-characterized swallowing
diffuculties in EoE.\textsuperscript{4}

Pollen-food allergy syndrome (PFAS): PFAS was diagnosed in pollen
sensitized patients who demonstrated oropharyngeal symptoms
(itching/tingling, mild erythema, mild angioedema) triggered with pollen
cross-reactive food(s).\textsuperscript{6,8}

\textbf{Statistical analysis}

Statistical analysis was performed using the SPSS (Statistical Package
for Social Sciences) for Windows 22.0 (SPSS Inc, Chicago, IL).
Categorical variables were presented as numbers and percentages.
Continuous variables were presented as mean +- standard deviation or
median (interquartile range) depending on its distribution.

\textbf{RESULTS}

A total of 98 EoE patients aged \selectlanguage{english}[?] 7 years old were screened. Twenty
patients were excluded from the study because of lost to follow-up,
unreachability, and neurodevelopmental disorder. Finally, seventy-eight
patients (74.4\% male) with a median age of 13.5 years (IQR:8 years)
were included in the study. (Figure 1). Unpleasant and recurrent
symptoms that were distinct from dysphagia with certain foods were
described in 13 patients (76.9\% male). (Figure 1). The median age at
the onset of symptoms of these 13 patients was 12.5 years (IQR: 7
years). All of them had concomitant allergic rhinitis (AR) (23.1\%
perennial, 76.9\% seasonal) and two patients had ongoing IgE-mediated
food allergy (patient 9: anaphylaxis with tree-nuts, patient 12:
anaphylaxis with fish).

The symptoms existed before and after the EoE diagnosis in 10 patients
(77\%) and three patients (23\%), respectively. Almost all patients
described oropharyngeal itching and tingling. The most common triggering
foods were kiwi and hazelnut, respectively. The median time from food
ingestion to symptom onset was five minutes (IQR: 4 minutes), and the
median duration of symptom relief was 30 minutes (IQR: 15 minutes)
(Table 1).

PFAS was diagnosed in 12 patients, and FIRE in one patient (Figure 1).
This patient (patient 10) was a 16-year-old girl who described narrowing
and pressure in the retrosternal area after consuming pickled but not
fresh cucumber on repeated exposures. She had not experienced a similar
complaint before the diagnosis of EoE. The triggering foods of PFAS were
different from the ones responsible for anaphylaxis in two patients
(patient 9 and patient 12).

\textbf{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.\textsuperscript{4,5,7} Therefore, in our own EoE
series, we questioned and investigated the presence of FIRE in cases
aged \selectlanguage{english}[?]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.\textsuperscript{4} The
majority of EoE experts estimated the prevalence of FIRE symptoms in the
EoE population between \textless{}5\% and 20\%. On the other hand, the
estimated prevalence of FIRE by EoE patients was
39.7\%.\textsuperscript{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.\textsuperscript{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.\textsuperscript{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.\textsuperscript{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.\textsuperscript{9} It is also suggested that a
chemical irritation of the inflamed esophageal mucosa may cause symptoms
related to FIRE.\textsuperscript{4}

In adult patients with EoE, another well-defined IgE-mediated reaction
triggered by food is PFAS.\textsuperscript{10-12} However, data about
the comorbidity of PFAS in children with EoE is
limited.\textsuperscript{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\%).\textsuperscript{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.\textsuperscript{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.\textsuperscript{5} Therefore, we also believe that FIRE should be
specifically questioned in EoE cases, particularly those with identified
AR and/or PFAS.\textsuperscript{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.\textsuperscript{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.\textsuperscript{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.

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
  Steinbach EC, Hernandez M, Dellon ES. Eosinophilic Esophagitis and the
  Eosinophilic Gastrointestinal Diseases: Approach to Diagnosis and
  Management. J Allergy Clin Immunol Pract. 2018;6:1483-1495.
\item
  Licari A, Votto M, D'Auria E, et al. Eosinophilic Gastrointestinal
  Diseases in Children: A Practical Review. Curr Pediatr Rev.
  2020;16:106-114.
\item
  Egritas Gurkan O, Ozturk H, Karagol HIE, et al. Primary Eosinophilic
  Gastrointestinal Diseases Beyond Eosinophilic Esophagitis in Children.
  J Pediatr Gastroenterol Nutr. 2021;72:294-299.
\item
  Biedermann L, Holbreich M, Atkins D, et al. Food-induced immediate
  response of the esophagus-A newly identified syndrome in patients with
  eosinophilic esophagitis. Allergy. 2021;76:339-347.
\item
  Holbreich M, Straumann A. Features of food-induced immediate response
  in the esophagus (FIRE) in a series of adult patients with
  eosinophilic esophagitis. Allergy. 2021;76:2893-2895.
\item
  Carlson G, Coop C. Pollen food allergy syndrome (PFAS): A review of
  current available literature. Ann Allergy Asthma Immunol.
  2019;123:359-365.
\item
  Votto M, Naso M, De Filippo M, et al. Food-induced immediate response
  of the esophagus: A first report in the pediatric age. Allergy.
  2022;77:711-712.
\item
  Poncet P, Senechal H, Charpin D. Update on pollen-food allergy
  syndrome. Expert Rev Clin Immunol. 2020;16:561-578.
\item
  Warners MJ, Terreehorst I, van den Wijngaard RM, et al. Abnormal
  Responses to Local Esophageal Food Allergen Injections in Adult
  Patients With Eosinophilic Esophagitis. Gastroenterology.
  2018;154:57-60.e2.
\item
  Cross-reactive food and pollen allergens most commonly involved in
  oral allergy syndrome in adults with eosinophilic esophagitis. Shim,
  Jane et al. Journal of Allergy and Clinical Immunology, Volume 151,
  Issue 2, AB90
\item
  Letner D, Farris A, Khalili H, et al. Pollen-food allergy syndrome is
  a common allergic comorbidity in adults with eosinophilic esophagitis.
  Dis Esophagus. 2018;31(2).
\item
  Mahdavinia M, Bishehsari F, Hayat W, et al. Association of
  eosinophilic esophagitis and food pollen allergy syndrome. Ann Allergy
  Asthma Immunol. 2017;118:116-117.
\item
  Sessions J, Purington N, Wang Y, McGhee S, et al. Pediatric
  eosinophilic esophagitis outcomes vary with co-morbid eczema and
  pollen food syndrome. Front Allergy. 2022;3:981961.
\item
  Ertoy Karagol H\selectlanguage{polish}İ, \selectlanguage{english}Yapar D, E\selectlanguage{polish}ğ\selectlanguage{english}rita\selectlanguage{polish}ş \selectlanguage{english}G\selectlanguage{ngerman}ürkan Ö, et al. Reliability and
  Validity Study of Turkish Version of Pediatric Eosinophilic
  Esophagitis Symptom Scores® (Tr-PEESS v2.0) Led to Development of a
  New Pediatric Eosinophilic Esophagitis Scale: GaziESAS. Turk J
  Gastroenterol. 2021;32:365-373.
\end{enumerate}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllllllll@{}}
\toprule
\begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{Patient}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{1}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{2}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{3}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{4}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{5}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{6}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{7}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{8}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{9}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{10}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{11}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{12}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{13}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Sex}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Female\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Female\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Female\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Male\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Age at symptom onset (years)}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15.4\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
13.5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
11.8\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
12.5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
17.9\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
14.5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
9.7\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
18\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8.8\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
16\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
7.7\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8.1\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
7.1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{AR\textsuperscript{++} (SAR\textsuperscript{§}/
PAR\textsuperscript{¶})}\selectlanguage{ngerman}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
SAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
PAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
SAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
SAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
SAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
SAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
PAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
SAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
SAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
SAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
SAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
SAR\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
PAR\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Symptoms}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Narrowing, pressure\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Itching, tingling\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Symptom} \textbf{region}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Retro-sternal area\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Oro-pharyngeal cavity\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Time to onset (minutes)}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
10\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Duration time (minutes)}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
10\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
30\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
30\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
30\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
30\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
30\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
30\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
20\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
30\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
20\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\selectlanguage{ngerman}\textbf{Severity\textsuperscript{¥} (1-10)}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Culprit foods}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Kiwi\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Banana Hazelnut Walnut Pistachio\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Hazelnut\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Eggplant\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Kiwi Orange Tangerine\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Persimmon\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Eggplant\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Kiwi\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Pumpkin seed\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Pickled cucumber\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Kiwi Banana Persimmon Hazelnut\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Carrot Cucumber Apple Walnut Almond\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Strawberry Kiwi Orange Tangerine Spinach\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{TABLE 1} Characteristics of children with EoE+ exhibiting
immediate, unpleasant, and recurrent symptoms associated with spesific
foods

\emph{\textsuperscript{\textbf{+}EoE: Eosinophilic esophagitis; ++AR:
Allergic rhinitis; §SAR: Seasonal AR; ¶PAR: Perennial AR; ¥Raiting on a
scale from 1-10, with 10 being the strongest}}\selectlanguage{ngerman}

\selectlanguage{english}\textsuperscript{+PFAS: Pollen-food allergy syndrome; ++FIRE:
Food-induced immediate response of the esophagus}

\textbf{FIGURE 1} Study population

\selectlanguage{english}
\FloatBarrier
\end{document}

