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\begin{document}

\title{Should cashew and pistachio be clinically considered as one allergen?}



\author[1]{Enrica Manca}%
\author[1]{Nidhal Touati}%
\author[1]{Maria De Filippo}%
\author[1]{Elena Carboni}%
\author[1]{Lucia Diaferio}%
\author[1]{Pascal Demoly}%
\author[1]{Davide Caimmi}%
\affil[1]{University Hospital Centre Montpellier}%


\vspace{-1em}



  
  \date{May 23, 2024}


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\textbf{Should cashew and pistachio be clinically considered as one
allergen?}

\textbf{Authors} (Last Name and First Name): Manca
Enrica\textsuperscript{1,2}, Touati Nidhal\textsuperscript{1}, De
Filippo Maria\textsuperscript{1,3}, Carboni Elena\textsuperscript{1,4},
Diaferio Lucia\textsuperscript{1,5}, Demoly Pascal\textsuperscript{1,6},
Caimmi Davide\textsuperscript{1,6}

\textbf{Affiliations} :

1. Allergy Unit of the Department of Respiratory Diseases, University
Hospital of Montpellier, France.

2. Pediatric Unit, University Hospital of Foggia, Italy.

3. Pediatric Unit, Fondazione IRCCS Policlinico San Matteo, University
of Pavia, Italy.

4. Pediatric Unit, Ospedale Maggiore, ASST Cremona, Italy.

5. Department of Pediatrics, Giovanni XXIII Hospital, Aldo Moro
University of Bari, Bari, Italy.

6. UMR-S 1136 INSERM-Sorbonne Universit\selectlanguage{ngerman}é, Equipe EPAR -- IPLESP, Paris,
France.

\textbf{Running title:} Allergy to cashew and pistachio

\textbf{Corresponding author:}

Davide Caimmi, MD, PhD

Allergy Unit, Département de Pneumologie et Addictologie

Hôpital Arnaud de Villeneuve, CHU de Montpellier, Univ Montpellier,
France

371, Avenue du Doyen Gaston Giraud -- 34090 Montpellier (France)

Phone number +33630061134

Email address:\emph{davide.caimmi@gmail}.com

Word count: 1191

Number of tables: 2

This research did not receive any funding.

The Authors declare no conflict of interest for the present paper.

\textbf{Keywords} : cashew nut, food allergy, oral food challenge,
pistachio, predictive values.

To the Editor,

The prevalence of food allergy has increased over the last decade,
affecting 1-3\% of the general population and 6-8\% of
children\textsuperscript{1}. Tree nuts are the cause of 18-40\% of
food-induced anaphylaxis events and of more than 25\% of food allergy
related deaths\textsuperscript{2}. Thus, the fear for a life-threatening
allergic reaction after accidental exposure to an allergen has a
significant impact on the quality of life of both patients and their
families\textsuperscript{1,3}. Among tree nuts, the prevalence of cashew
allergy is increasing, being reported to cause even more severe
anaphylactic reactions than peanut allergy\textsuperscript{1,4}.

Cashew (CN) and pistachio share a phylogenetic origin and are members of
the \emph{Anacardiaceae} family. Both serological and clinical
cross-reactivity have been observed and may be explained by a high
degree of homology of their seed storage proteins Ana o 1/Pis v 3 (7S
vicilin; 78\%), Ana o 2/Pis v 2 (11S legumin; 80\%), and Ana o 3/Pis v 1
(2S albumin; 70\%)\textsuperscript{5,6}. For these reasons, some authors
refer to patients suffering from allergy to these nuts as presenting
with the cashew/pistachio syndrome\textsuperscript{8}.In children with
CN sensitization, an elimination diet is prescribed for both foods,
although oral food challenges (OFC) are essential to confirm or exclude
allergy to both\textsuperscript{6}\textsubscript{.}

Through a retrospective chart review, we aimed to assess the safety of
reintroduction of one of these two nuts at home based on negative
allergy testing for the other one. Our secondary objective was to
determine the concordance and predictive values of skin prick tests
(SPT) with the prick by prick method for OFC outcomes.

We included all patients admitted to the Allergy Unit of the University
Hospital of Montpellier, between January 2006 and March 2020, for
suspected allergy to CN and/or pistachio, based on clinical history
and/or positive SPT, who underwent open OFC for CN and/or pistachio. We
defined as ``allergic'' those patients with a positive OFC, based on
international guidelines for assessing OFC outcomes\textsuperscript{7}.
In each patient, we evaluated age, sex, comorbidities (asthma and atopic
dermatitis), results of SPT (positive when wheal size was \selectlanguage{english}[?] 3 mm),
specific IgE and OFC. Ana o 3 IgE were considered positive when
\textgreater{} 0,1 kUA/L. The study was approved by a local ethic
committee (IRB MPL202000401, Clinical Trial NCT04304586). Missing data
were included in the determination of PPV and NPV and were considered
MAR.

We included 115 patients, with a median age of 9 years (3 years-20
years); 65 of them were males (56.5\%). Eighty-seven patients (75.7\%)
had positive SPT to CN, 99 (86.1\%) to pistachio and 77 to both
(67.0\%). Cashew SPT data were missing for 3 patients, and pistachio SPT
was missing for 3 additional patients. Of 24 patients with a negative
SPT to CN, 20(83.3\%) had a positive SPT to pistachio. On the other
hand, 9(69\%) of the 13 patients with a negative SPT to pistachio had a
positive SPT to CN. Based on our results, the Positive and Negative
Predictive Value (PPV and NPV) of SPT to CN and pistachio are shown in
Table 1.

Among the 115 patients who underwent an OFC, 37 were tested to both
nuts, 41 only to cashew and37 only to pistachio (Table 2). OFC was
positive for both nuts in 5 patients (4.3\%), who presented non-severe
cutaneous reactions in 3 cases during both tests, whereas the other 2
presented anaphylactic reactions during both OFC.

Among our patients with a positive OFC to cashew (32), only 4 had
negative IgE for Ana o 3. However, using a cut-off level of 2 kUA/L, we
found that Ana o 3 had a PPV of 64.3\% (35.1-87.2\%, 95\%CI) for a
positive CN OFC, considering 11 missing data of Ana o 3 level. Eleven
patients (34.3\%) did not have a prior history of clinical reactivity to
CN, 11 (34.3\%) reported a history of anaphylaxis, and 10 (31.2\%)
reported non-severe cutaneous reactions.

Of the 46 patients with negative CN OFC, 22 underwent OFC to pistachio.
All of them were negative. Among these patients, 20 (91\%) had positive
pistachio SPT and IgE, 1 (4.5\%) had positive pistachio SPT but negative
IgE and 1 (4.5\%) had negative both SPT and IgE. Of the other 24
patients who weren't challenged, 11 (45\%) had positive allergic workup
(both SPT and IgE) to pistachio, 4 (16.7\%) had positive SPT only, 2
(8.3\%) had negative SPT but positive IgE and 5 (20.8\%) had negative
SPT.

Among 19 patients (16.5\%) who had a positive pistachio OFC, 15 (78.9\%)
had no reported history of allergic reaction to pistachio, 3 (15.8\%)
had prior non-severe cutaneous reactions and 1 (5.3\%) reported a
history of anaphylaxis (Table 2).

Among the fifty-six patients with a negative pistachio OFC, 11 (14.7\%)
had a positive CN OFC and 22 had a negative CN OFC. Among these 22
patients, 17 (77\%) had positive CN SPT and IgE with Ana o 3 positive in
4 (18.2\%) patients and negative in 7 (41\%).

Moreover, 18 (94.7\%) of the 19 patients with a positive pistachio OFC
had positive CN SPT, but only 5 of these had a positive CN OFC; on the
contrary, 34 of the 56patients with negative pistachio OFC (60.7\%) had
a positive CN SPT, and, among these, only 11(32\%) had a positive CN
OFC.

Considering missing data, PPV and NPV of OFC are shown in Table1.

By presenting these data, we want to highlight the differences in both
sensitization and allergy between CN and pistachio. As reported in the
Improvement of Diagnostic mEthods for Allergy assessment (IDEAL) study,
98\% of cashew-sensitized patients were co-sensitized to pistachio, and
CN is often the primary sensitizer (the first nut the patient is
sensitized to)\textsuperscript{6}. Compared to this study, our results
demonstrated a lower rate of 67\% cashew/pistachio co-sensitization.

In accordance with findings from prior publications, in our study, serum
IgE to Ana o3 showed an excellent diagnostic accuracy, suggesting that
Ana o3 may be used in clinical practice to predict the likelihood of
clinical reactivity and outcomes of an OFC to
cashew\textsuperscript{8,9}. However, using a cut-off level of 2 kUA/L
as described by Lange et al, only 9 of our 32 patients (28.1\%) allergic
to CN would have correctly been identified without an OFC, whereas 12
(37.5\%) would have been incorrectly classified as tolerant.
Nevertheless, the cut-off level was accurate in predicting tolerant
patients, among which only 1 of 46 (2.2\%) had higher level of Ana
o3\textsuperscript{9}.Furthermore, our results did not demonstrate a
statistically significant correlation between the severity of reaction
and the levels of IgE to Ana o 3.

In conclusion, we could say that it is safe to introduce pistachio at
home if patients have a negative OFC to CN, independently from its SPT
and IgE, and that when an OFC to pistachio is positive, the patient is
highly likely to be allergic to CN as well. Nevertheless, the data we
present come from a single center, are retrospective, and should be
strengthen and possibly confirmed by a prospective analysis. Therefore,
the safest conclusion, so far, is that CN and pistachio should be
considered as two different sources of allergens and a complete allergy
work-up for both, including OFC, should be performed, before authorizing
a safe reintroduction at home.

Manca E\textsuperscript{1,2}, Touati N\textsuperscript{1}, De Filippo
M\textsuperscript{1,3}, Carboni E\textsuperscript{1,4}, Diaferio
L\textsuperscript{1,5}, Demoly P\textsuperscript{1,6}, Caimmi
D\textsuperscript{1,6}

1. Allergy Unit of the Department of Respiratory Diseases, University
Hospital of Montpellier, France.

2. Pediatric Unit, University Hospital of Foggia, Italy.

3. Pediatric Unit, Fondazione IRCCS Policlinico San Matteo, University
of Pavia, Italy.

4. Pediatric Unit, Ospedale Maggiore, ASST Cremona, Italy

5. Department of Pediatrics, Giovanni XXIII Hospital, Aldo Moro
University of Bari, Bari, Italy.

6. UMR-S 1136 INSERM-Sorbonne Universite, Equipe EPAR - IPLESP, Paris,
France.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Sanchiz A, Cuadrado C, Dieguez MC, Ballesteros I, Rodriguez J, Crespo
  JF, et al. Thermal processingeffects on the IgE-reactivity of cashew
  and pistachio. Food Chem 2018;245:595-602.
\item
  Bock SA, Munoz-Furlong A, Sampson HA. Further fatalities caused by
  anaphylactic reactions to food, 2001-2006. J AllergyClinImmunol
  2007;119:1016--1018.
\item
  Smeekens J.M., Bagley K., KulisM. Tree Nut Allergies: Allergen
  Homology, Cross-Reactivity, and Implications for Therapy. Clin
  ExpAllergy 2018;48:762-772.
\item
  Saba L, Clerc-Urmes I, Delahaye C, Chevillot E, Jarlot-Chevaux S,
  Dumond P, et al. Predictive factors of allergy to pistachio in
  children allergic to cashew nut. Pediatr Allergy Immunol
  2020.\emph{Online ahead of print.}
\item
  Bastiaan-Net S, Reitsma M, Cordewener JHG, Van der Valk JPM, America
  TAHP, Dubois AEJ, et al. IgE Cross-Reactivity of Cashew Nut Allergens.
  Int Arch Allergy Immunol 2019;178:19-32.
\item
  Van der Valk JPM, Bouche RE, Gerth van Wijk R, de Groot H, Wichers HJ,
  Dubois AEJ, et al. Low percentage of clinically relevant pistachio nut
  and mango co-sensitisation in cashew nut sensitised children.
  ClinTransl Allergy 2017;7:8.
\item
  Bindslev-Jensen C, Ballmer-Weber BK, Bengtsson U, Blanco C, Ebner C,
  Hourihane J, et al. Standardization of food challenges in patients
  with immediatereactions to foods -- position paper from the European
  Academyof Allergology and Clinical Immunology. Allergy
  2004;59:690\selectlanguage{english}-697.
\item
  Savvatianos S, Konstantinopoulos AP, Borga A, Stavroulakis G,
  LidholmJ, Borres MP et al. Sensitization to cashew nut 2S albumin, Ana
  o 3, is highly predictive of cashew and pistachio allergy in Greek
  children. J Allergy Clin Immunol 2015;136:192-194.
\item
  Lange L, Lasota L, Finger A, Vlajnic D, Busing S, Meister J, et al.
  Ana o 3-specific IgE Is a Good Predictor for Clinically Relevant
  Cashew Allergy in Children. Allergy 2017;72:598-603.
\item
  Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA,
  Branum A, et al. Second symposium on the definition and management of
  anaphylaxis: summary report- Second National Institute of Allergy and
  Infectious Disease/Food Allergy and Anaphylaxis Network Symposium. J
  Allergy Clin Immunol 2006;117:391-397.
\end{enumerate}

\textbf{Table 1} -- Predictive Values for SPT and OFC found in our
study.\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
& & & \emph{Predictive values} & \emph{95\%CI*}\tabularnewline
\midrule
\endhead
SPT & Positive for CN & PPV & 35.6\% for CN allergy &
25.6-46.6\%\tabularnewline
& & & 88.5\% for positive SPT to pistachio & 79.9-94.3\%\tabularnewline
& Positive for pistachio & & 19.2\% for pistachio allergy &
12.0-28.4\%\tabularnewline
& & & 77.8\% for positive SPT to CN & 68.3-87.5\%\tabularnewline
& Negative for CN & NPV & 16\% for negative SPT to pistachio &
4.6-35.9\%\tabularnewline
& Negative for pistachio & & 30.8\% for negative SPT to CN &
9.1-61.4\%\tabularnewline
OFC & Positive for CN & PPV & 15.6\% for a positive OFC to pistachio &
5.3-32.8\%\tabularnewline
& Positive for pistachio & & 26.3\% for a positive OFC to CN &
9.1-51.2\%\tabularnewline
& Negative for CN & NPV & 47.8\% for a negative OFC to pistachio &
32.9-63\%\tabularnewline
& Negative for pistachio & & 19.6\% for a negative OFC to CN &
26.5-53.2\%\tabularnewline
\bottomrule
\end{longtable}

\textbf{Legend} -- SPT: Skin Prick Tests; OFC: Oral Food Challenge; PPV:
Positive Predictive Value; NPV: Negative Predictive Value; CN: Cashew
Nut; CI: Confidence Interval; Positive SPT: wheal size \textgreater{}3
mm.

* Exact method

\textbf{Table 2} -- Clinical characteristics of patients undergoing OFC
to pistachio and cashew.\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Pistachio OFC: positive n=19 (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Pistachio OFC: negative n=56 (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\emph{p-value}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Cashew OFC: positive n=32 (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Cashew OFC: negative n=46 (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\emph{p-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Socio-demographic characteristics Sex Male Female Age during test

\subsection*{[?] 12 years old}

{\label{years-old}} \textless{}12 years old\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
16(21.3) 3(4) 6 (5.2) 13 (11.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
29(38.6) 27(36) 15(13.1) 39(33.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.01 0.75\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
18(23) 14(17.9) 5(6.5) 27(35)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
25(32) 21(26.9) 12(15.6) 33(42.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.87 0.25\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Comorbidities Asthma Yes\\
No Eczema Yes No\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
13(17.3) 6(8) 4(5.3) 15(20)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
35(46.7) 21(28) 13(17.3) 43(57.3)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.8 1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
18(23) 14(17.9) 11(14.1) 8(10.3)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
30(38.5) 16(20.5) 21(26.9) 38(48.7)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.42 0.08\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Reported reaction in clinical history+ Absent Grade I Grade II and
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
15(20) 3(4) 1(1.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
45(60) 6(8) 5(6.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.78\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
11(14.1) 10(12.8) 11(14.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
31(39.7) 7(9) 8(10.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.01}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Pistachio OFC Negative (n=56) Positive (n=19) Not performed (n=40)
Negative Pistachio SPT\\
Lost during follow-up\\
Not performed yet\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
11(0.9) 5(4.3) 17(14.7) 2 (4.9) 3 (7.3) 11 (26.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
22(19.8) 0(0) 24(20.8) 6 (14.6) 2 (4.9) 16 (39)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.008}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Pistachio wheal size \textless{} 3 mm\\
[?] 3 mm Pistachio IgE (KUA/l) \textless{} 4.14\\
[?] 4.14\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0(0) 19(25.3) 16(21.3) 3(4)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4(5.3) 52(69.3) 51(69.3) 4(5.3)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.56 0.36\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4(5.3) 27(36) 25(38.5) 5(7.7)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
8(10.7) 36(48) 31(47.7) 4(6.1)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.75 0.72\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Cashew OFC Negative (n=46) Positive (n=32) Not performed (n=37) Negative
CN SPT\\
Lost during follow-up\\
Not performed yet\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0(0) 5(6.7) 14(18.7) 1 (2.7) 3 (8.1) 10 (27)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
22(29.3) 11(14.7) 23(30.7) 16 (62.2) 2 (5.4) 5 (13.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.008}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Cashew wheal size \textless{} 3 mm\\
[?] 3 mm Cashew IgE (KUA/l) \textless{} 1.125\\
[?] 1.125 Ana o 3 IgE (KUA/l) \textless{} 2\\
[?] 2\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1(1.3) 18(24.3) 10(15.9) 9(14.3) 4(11.1) 6(16.7)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
20(27) 33(44.6) 31(49.2) 13(20.6) 24(66.7) 2(5.6)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{0.08} 0.25 \textbf{0.002}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0(0) 31(40.3) 15(20.2) 14(18.9) 12(24) 9(18)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
8(10.4) 38(49.3) 29(39.1) 16(21.6) 28(56) 1(2)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{0.02} 0.27 \textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Cut-off for specific IgE levels are based on the articles by Lange et
al. and Cetinkaya t al. {[}4,9{]}. +Grading of anaphylaxis based on the
article by Sampson et al {[}10{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Cut-off for specific IgE levels are based on the articles by Lange et
al. and Cetinkaya t al. {[}4,9{]}. +Grading of anaphylaxis based on the
article by Sampson et al {[}10{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Cut-off for specific IgE levels are based on the articles by Lange et
al. and Cetinkaya t al. {[}4,9{]}. +Grading of anaphylaxis based on the
article by Sampson et al {[}10{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Cut-off for specific IgE levels are based on the articles by Lange et
al. and Cetinkaya t al. {[}4,9{]}. +Grading of anaphylaxis based on the
article by Sampson et al {[}10{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Cut-off for specific IgE levels are based on the articles by Lange et
al. and Cetinkaya t al. {[}4,9{]}. +Grading of anaphylaxis based on the
article by Sampson et al {[}10{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Cut-off for specific IgE levels are based on the articles by Lange et
al. and Cetinkaya t al. {[}4,9{]}. +Grading of anaphylaxis based on the
article by Sampson et al {[}10{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Cut-off for specific IgE levels are based on the articles by Lange et
al. and Cetinkaya t al. {[}4,9{]}. +Grading of anaphylaxis based on the
article by Sampson et al {[}10{]}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Legend} -- OFC: Oral Food Challenge.

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