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\begin{document}

\title{Prognosis of infantile food protein-induced enterocolitis syndrome to
wheat: A case series}



\author[1]{Noriyuki Yanagida}%
\author[1]{Makoto Nishino}%
\author[1]{Sakura Sato}%
\author[1]{Ken-ichi Nagakura}%
\author[1]{Kyohei Takahashi}%
\author[1]{Kiyotake  Ogura}%
\author[1]{Motohiro Ebisawa}%
\affil[1]{Kokuritsu Byoin Kiko Sagamihara Byoin}%


\vspace{-1em}



  
  \date{May 18, 2024}


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\textbf{Prognosis of infantile food protein-induced enterocolitis
syndrome to wheat: A case series}

Makoto Nishino\textsuperscript{1,2} \textbar{} Noriyuki
Yanagida\textsuperscript{1,3,*} \textbar{} Sakura
Sato\textsuperscript{1} \textbar{} Ken-ichi
Nagakura\textsuperscript{3,4} \textbar{} Kyohei
Takahashi\textsuperscript{3} \textbar{}Kiyotake
Ogura\textsuperscript{3}\textbar{} Motohiro Ebisawa\textsuperscript{1}

\textsuperscript{1} Clinical Research Center for Allergy and
Rheumatology, National Hospital Organization Sagamihara National
Hospital, Kanagawa, Japan

\textsuperscript{2} Department of Pediatrics, Ushiku Aiwa General
Hospital, Ibaraki, Japan

\textsuperscript{3} Department of Pediatrics, National Hospital
Organization Sagamihara National Hospital, Kanagawa, Japan

\textsuperscript{4} Department of Pediatrics, Jikei University School of
Medicine, Tokyo, Japan

\textsuperscript{\textbf{*}}\textbf{Corresponding author:} Noriyuki
Yanagida

Department of Pediatrics, National Hospital Organization Sagamihara
National Hospital,

18-1, Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan

E-mail:\emph{sagami@foodallergy.jp}

\textbf{Word count:} 1,191

\textbf{Number of figures:} 2 \textbf{Number of tables:} 1

\textbf{Prognosis of infantile food protein-induced enterocolitis
syndrome to wheat: A case series}

\textbf{Conflict of interest:} Motohiro Ebisawa and Sakura Sato have
received speaker honoraria from Viatris. The other authors declare that
they have no conflicts of interest.

\textbf{Financial support:} This research received no specific grant
from any public, commercial, or not-for-profit funding agency.

\textbf{Keywords:} Food protein-induced enterocolitis syndrome;
Tolerance; Prognosis; Wheat

To the Editor,

Food protein-induced enterocolitis syndrome (FPIES) is a type of
non-IgE-mediated food allergy characterized by repetitive vomiting 1--4
h after ingestion of any food.\textsuperscript{1}FPIES is commonly
caused by foods such as cow's milk, soy, hen's egg, fish, rice, and oat,
varying in prevalence by geographical region; however, wheat-induced
FPIES (wheat-FPIES) is relatively rare.\textsuperscript{2-4} In Japan,
the incidence of wheat-FPIES has been reported to be increasing, along
with FPIES to cow's milk, egg, and soy.\textsuperscript{5} However, to
our knowledge, no study has reported the clinical features and tolerance
acquisition of wheat-FPIES. Therefore, this study aimed to describe the
clinical characteristics of wheat-FPIES and the prognosis at the age of
5 years.

We retrospectively reviewed children who visited our hospital from May
2012 to July 2018 with a suspected diagnosis of wheat-FPIES. The
diagnostic criteria proposed by Nowak-W\selectlanguage{polish}ę\selectlanguage{english}grzyn et al. were used in the
study. Infants who either fulfilled the diagnostic criteria based on the
history of symptoms or symptoms observed during oral food challenge
(OFC) were defined as wheat-FPIES patients.\textsuperscript{1} Those who
were followed up to age 5 years were included in the study. Wheat- and
\selectlanguage{greek}ω-\selectlanguage{english}5-gliadin-specific immunoglobulin E (sIgE) levels were measured using
ImmunoCAP (Thermo Fisher Scientific/Phadia, Uppsala, Sweden) at the
first visit. Sensitization was defined as a sIgE level of [?]0.35.

All the patients received OFCs with 52 or 390 mg of wheat protein in the
form of boiled udon noodles for diagnosis or to confirm tolerance to the
amount challenged. Patients who passed their initial OFC proceeded to
confirm if they could tolerate 2,600 mg (equivalent to the amount of
wheat protein in half a slice of bread) by receiving stepwise OFCs, by
gradually increasing the amount consumed at home, or by a combination of
the two. Stepwise OFCs were performed by sequentially increasing the
dose from 52 mg to 390, 1300, and [?]2,600 mg on separate days when the
preceding OFC was negative. When a patient failed any OFC, it was
repeated after 6--18 months. The children were considered to have
achieved tolerance when they could consume 2,600 mg without any
symptoms. All OFCs were performed in the hospital under the supervision
of a physician. The challenge amount was administered in a single dose
with monitoring for at least 5 hours. OFCs were determined to be
positive when vomit was induced after \textgreater{}1 hour, and no
IgE-mediated skin or respiratory symptoms were observed.

A total of 11 patients were suspected of having wheat-FPIES. Seven
patients fulfilled the diagnostic criteria based on their history of
symptoms, of which one patient was excluded because he had only been
followed up to the age of 2 years. Of the remaining 4 patients, one
presented with repetitive vomiting, lethargy, and pallor during OFC and
therefore fulfilled the diagnostic criteria based on symptoms during the
OFC. In total, 7 patients were included in the study (Figure 1).

Table 1 presents the characteristics of the 7 patients. The median age
at the onset of symptoms was 7 (range: 6--9) months, and the median age
at the first visit to our hospital was 13 (range: 8--17) months. The
patients had experienced a median of 4 episodes of vomiting before their
first visit. Data concerning wheat consumption before the first episode
of symptoms was available for 5 patients, and they had all previously
consumed wheat without any symptoms. Overall, 2 (29\%) patients had
comorbid atopic dermatitis, one had IgE-mediated egg allergy, and two
had FPIES to a different food. All patients were not sensitized to
\selectlanguage{greek}ω-\selectlanguage{english}5-gliadin; however, one patient had a slightly elevated wheat-sIgE
level of 0.42 kU\textsubscript{A}/L.

Initial OFCs were performed at a median age of 18 (range: 8--45) months.
The proportion of patients who became tolerant to wheat increased with
age, and at the age of 5 years, 6 (86\%) patients were confirmed to have
achieved tolerance, and the remaining patient was able to consume 52 mg
of wheat protein (Figure 2). The patient sensitized to wheat achieved
tolerance at the age of four. The patient who was not confirmed to have
achieved tolerance at the age of 5 years had a positive initial OFC to
52 mg at 45 months and underwent a repeat OFC with the same dose at 62
months, which was negative. Whether the patient could consume larger
amounts was not examined at the time because he refused to eat during
the following OFCs. Among the 6 patients who achieved tolerance, 2
patients gradually increased the amount consumed at home after a
negative OFC with 390 mg, 2 patients received stepwise OFCs up to 1,300
mg and then gradually increased the amount consumed at home, and 2
patients received stepwise OFCs up to [?]2,600 mg. The median age of the
last reaction to wheat was 18 (range: 8-45) months, and the median time
from the last reaction to when the patient was confirmed to have
acquired tolerance was 24 (range: 5-32) months.

In this study, although the number of patients is limited, we found that
most Japanese infants with wheat-FPIES achieved tolerance by 5 years.
Patients with solid FPIES have been considered to acquire tolerance
later than those with FPIES to cow's milk and soy.\textsuperscript{6-8}
However, recent studies from the US have reported tolerance for FPIES to
cow's milk at approximately 5 years of age.\textsuperscript{3,5}
Patients with solid FPIES to grains such as oat and rice have been
reported to acquire tolerance at a median age of 4 and 4.7 years,
respectively.\textsuperscript{3} In Spain, 75\% of patients with FPIES
to egg and fish have been reported to achieve tolerance by the age of 5
years .\textsuperscript{9} The rate of tolerance acquisition in Japanese
children with wheat-FPIES in our study was comparable to these previous
results, with 86\% of the patients acquiring tolerance by the age of 5
years. These results suggest that although a subset of patients may have
prolonged FPIES, most patients achieve tolerance before school age.

Caubet et al. have reported that for patients with FPIES to cow's milk,
sensitization to milk was a factor that predicted poor
outcomes.\textsuperscript{3} However, the patient sensitized to wheat in
our study achieved tolerance at the age of 4 years.

A study limitation is that owing to the retrospective nature, the age at
initial OFCs, the intervals between stepwise OFCs, and the rate at which
the dose consumed at home was increased varied across patients. In
addition, when OFCs were positive, they were repeated after a period of
6--18 months. Only after repeated OFCs were confirmed to be negative,
did the patients receive the proceeding stepwise OFCs and/or increase
the amount consumed at home to confirm tolerance. Thus, it took a median
of 24 months from the last reaction caused by wheat to the time
tolerance was confirmed. Therefore, some of the patients assumably
achieved tolerance earlier than it is described in our study.

In conclusion, most Japanese infants with wheat-FPIES in our study
acquired tolerance by the age of 5 years. OFCs must be repeated to
assess tolerance, given that most patients outgrow their wheat-FPIES
before school age. Further prospective studies are warranted with
routine OFCs to determine a more accurate prognosis.

Makoto Nishino\textsuperscript{1,2}, MD; Noriyuki
Yanagida\textsuperscript{1,3}, MD; Sakura Sato\textsuperscript{1}, MD;
Ken-ichi Nagakura\textsuperscript{3,4}, MD, PhD; Kyohei
Takahashi\textsuperscript{3}, MD, PhD; Kiyotake
Ogura\textsuperscript{1}, MD, PhD; Motohiro Ebisawa\textsuperscript{3},
MD, PhD.

\textsuperscript{1} Clinical Research Center for Allergy and
Rheumatology, National Hospital Organization Sagamihara National
Hospital, Kanagawa, Japan

\textsuperscript{2} Ushiku Aiwa General Hospital, Ibaraki, Japan

\textsuperscript{3} Department of Pediatrics, National Hospital
Organization Sagamihara National Hospital, Kanagawa, Japan

\textsuperscript{4} Department of Pediatrics, Jikei University School of
Medicine, Tokyo, Japan

\textbf{Author Contributions}

Makoto Nishino: Conceptualization (lead); formal analysis (lead);
writing -- original draft (lead). Noriyuki Yanagida: Methodology
(equal); writing -- original draft (supporting); writing -- review and
editing (lead). Sakura Sato: Methodology (equal); writing -- original
draft (supporting); writing -- review and editing (lead). Kyohei
Takahashi: writing -- review and editing (equal). Nagakura: writing --
review and editing (equal). Kiyotake Ogura: writing -- review and
editing (equal). Motohiro Ebisawa: Methodology (equal); writing --
review and editing (lead).

\textbf{Acknowledgments}

We would like to thank Editage (www.editage.com) for their assistance
with English language editing. This research received no specific grant
from any funding agency in the public, commercial, or not-for-profit
sectors.

\textbf{Key Message}

The rate of tolerance acquisition in infants with food protein-induced
enterocolitis syndrome caused by wheat increased with age and resolved
in most patients by the age of 5 years. Oral food challenges should be
repeated regularly to assess for tolerance acquisition.

\textbf{Ethical Approval}

Written informed consent was obtained from the guardian of the patient
before each oral food challenge. The study was approved by the Ethical
Committee Board of Sagamihara National Hospital.

\textbf{Data Sharing and Data Accessibility}

The data that support the findings of this study are available on
request from the corresponding author. The data are not publicly
available due to privacy or ethical restrictions.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Nowak-W\selectlanguage{polish}ę\selectlanguage{english}grzyn A, Chehade M, Groetch ME, et al. International consensus
  guidelines for the diagnosis and management of food protein-induced
  enterocolitis syndrome: Executive summary-Workgroup Report of the
  Adverse Reactions to Foods Committee, American Academy of Allergy,
  Asthma \& Immunology. J Allergy Clin Immunol 2017;139:1111-1126.e4.
\item
  Cianferoni A. Food protein-induced enterocolitis syndrome
  epidemiology. Ann Allergy Asthma Immunol 2021;126:469-477.
\item
  Caubet JC, Ford LS, Sickles L, et al. Clinical features and resolution
  of food protein-induced enterocolitis syndrome: 10-year experience. J
  Allergy Clin Immunol 2014;134:382-389.
\item
  Ruffner MA, Ruymann K, Barni S, Cianferoni A, Brown-Whitehorn T,
  Spergel JM. Food protein-induced enterocolitis syndrome: insights from
  review of a large referral population. J Allergy Clin Immunol Pract
  2013;1:343-349.
\item
  Akashi M, Hayashi D, Kajita N, et al. Recent dramatic increase in
  patients with food protein-induced enterocolitis syndrome (FPIES)
  provoked by hen's egg in Japan. J Allergy Clin Immunol Pract
  2022;10:1110-1112.e2.
\item
  Lee E, Campbell DE, Barnes EH, Mehr SS. Resolution of acute food
  protein-induced enterocolitis syndrome in children. J Allergy Clin
  Immunol Pract 2017;5:486-488.e1.
\item
  Hwang JB, Sohn SM, Kim AS. Prospective follow-up oral food challenge
  in food protein-induced enterocolitis syndrome. Arch Dis Child
  2009;94:425-428.
\item
  Katz Y, Goldberg MR, Rajuan N, Cohen A, Leshno M. The prevalence and
  natural course of food protein-induced enterocolitis syndrome to cow's
  milk: a large-scale, prospective population-based study. J Allergy
  Clin Immunol 2011;127:647-53.e1-3.
\item
  Vazquez-Ortiz M, Machinena A, Dominguez O, et al. Food protein-induced
  enterocolitis syndrome to fish and egg usually resolves by age 5 years
  in Spanish children. J Allergy Clin Immunol Pract 2017;5:512-515.e1.
\end{enumerate}

\textbf{Table 1} . Characteristics of the seven patients with
wheat-induced food protein-induced enterocolitis syndrome\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
\begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Patient\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
7\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Sex\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Female\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Female\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Male\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Age of onset (months)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
7\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
9\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
9\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
7\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
7\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Age at first visit (months)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
9\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
13\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
17\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
16\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
17\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
11\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Fulfilled diagnostic criteria based on history\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Fulfilled diagnostic criteria based on OFC\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
History of symptoms owing to wheat consumption\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Vomiting 2--4 hours after eating a food containing wheat\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Two or more episodes of repetitive vomiting after eating the same
food\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Episodes of repetitive vomiting 1--4 hours after eating 2 or more
different foods\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Number of vomiting episodes before first visit\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Extreme lethargy with a suspected reaction\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Marked pallor with any suspected reaction\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Visit to emergency department due to a suspected reaction\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Requirement of intravenous fluid due to a suspected reaction\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Diarrhea (within 24 hours)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Hypotension\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Hypothermia\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
IgE-mediated skin and/or respiratory symptoms\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Total IgE (IU/mL)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
13.2\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
11.1\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}5.0\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
19.2\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
7.1\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
129\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
12.2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Wheat-sIgE (kU\textsubscript{A}/L)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.42\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\selectlanguage{greek}ω-\selectlanguage{english}5-gliadin sIgE (kU\textsubscript{A}/L)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.35\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Current complications\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Atopic dermatitis\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Recurrent wheezing\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
IgE-mediated food allergy\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
+ (egg)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
FPIES (other than wheat)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
+ (fish)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
+ (barley)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Age at last reaction to wheat (months)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
28\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
14\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
10\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
18\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
19\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
45\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Age at which tolerance was confirmed (months)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
44\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
34\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
42\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
48\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
47\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
NA\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
13\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Diagnostic criteria refer to those proposed in the international
consensus guidelines for the diagnosis and management of food
protein-induced enterocolitis syndrome. Patients who either met the
diagnosis criteria based on their history of symptoms or symptoms
exhibited during OFC were defined as wheat-FPIES patients.

Abbreviations: OFC, oral food challenge; FPIES, food protein-induced
enterocolitis syndrome; sIgE, specific immunoglobulin E; NA, not
applicable

\textbf{Figure Legends}

\textbf{Figure 1.} Selection of patients with wheat-FPIES included in
the study. Seven patients fulfilled the diagnostic criteria based on the
history of symptoms, of which one patient was excluded because they were
not followed up to the age of five. One patient presented with
repetitive vomiting, lethargy, and pallor during OFC and therefore
fulfilled the diagnostic criteria based on symptoms during OFC.

Abbreviations: FPIES, food protein-induced enterocolitis syndrome; OFC,
oral food challenge

\textbf{Figure 2.} Tolerance acquisition rate of the seven patients who
were followed up to the age of 5 years. Patients were defined to be
tolerant to wheat when they could consume 2,600 mg of wheat protein
(equivalent to the amount of wheat protein in half a slice of bread,).

The patient who was not confirmed to have achieved tolerance at the age
of 5 years was capable of consuming 52 mg but whether he could consume
larger amounts could not be determined because of refusal of eating
during the following OFCs.

\textbf{Hosted file}

\verb`Figure_1.pptx`  available at \url{https://authorea.com/users/368766/articles/595784-prognosis-of-infantile-food-protein-induced-enterocolitis-syndrome-to-wheat-a-case-series}

\textbf{Hosted file}

\verb`Figure_2.pptx`  available at \url{https://authorea.com/users/368766/articles/595784-prognosis-of-infantile-food-protein-induced-enterocolitis-syndrome-to-wheat-a-case-series}

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

