A remarkable food allergy in children: cashew nut allergy

Abstract

Objective:
The prevalence of cashew nut allergy is increasing. Clinical reaction to cashew nuts may be severe, including anaphylaxis. In this study, we aimed to evaluate the frequency of cashew nut sensitivity in a group of children with food allergy and the clinical features and course of cashew nut allergy.

Material and methods:
A retrospective chart review was performed on 516 children who presented with food allergy at a pediatric allergy department. Individuals sensitized to cashew nuts were examined.

Results:
Cashew nut sensitization was detected in 17 (64.7% male; mean age of symptom onset, 14 months) of 516 patients with food allergy. Skin symptoms were the most frequent clinical presentation, followed by gastrointestinal symptoms. Overall, 29.4% of the patients presented with anaphylaxis. All anaphylactic reactions were developed after the first consumption of cashew nuts. Of the cashew nut-sensitized patients, 82.3% were diagnosed with moderate-to-severe atopic dermatitis, and all of them had multiple food allergies. During the follow-up, 90% of the patients who had cashew nut sensitization and co-existing food allergies to cow's milk and/or hen's egg developed tolerance to cow's milk and/or hen's egg, but none of the patients could tolerate cashew nut ingestion.

Conclusion:
Cashew nut is a potent allergen, causing severe allergic reactions that persist long term compared with other food allergies. Early onset of moderate-to-severe atopic dermatitis and multiple food allergies are remarkable co-existing conditions in children who have been diagnosed with cashew nut allergy. Pediatricians should be aware of this emerging food allergy.

Full text

Turkish
Archiv es of
Pediatrics
ORIGINAL ARTICLE
DOI: 10.5152/TurkArchPediatr.2020.20111
A remarkable food allergy in children: cashew nut allergy
Ayşegül Ertuğrul , İlknur Bostancı , Serap Özmen
Department of Pediatric Allergy and Immunology, Health Science University Dr. Sami Ulus Maternity and Children Training and Research Hospital, Ankara,
Turkey
What is already known
on this topic?
• Recent studies on cashew nut
allergy suggest that the prev-
alence of cashew nut allergy
is increasing with raising con-
sumption. Clinical reaction to
cashew nuts may be severe,
suggesting high potency com-
parable with other tree nuts
and peanuts. The allergen-
ic potential of cashew nuts is
an underestimated important
healthcare problem.
What this study adds on
this topic?
• Most of the children in this study
were sensitized to cashew nuts
without ever consuming ca-
shew nuts in the infancy period.
Early onset of moderate-to-se-
vere atopic dermatitis and mul-
tiple food allergies are remark-
able co-existing conditions in
children who have been diag-
nosed with a cashew nut aller-
gy. Cashew nut allergy is asso-
ciated with a significant risk of
anaphylaxis; therefore, ana-
phylaxis should be considered
when evaluating children with
suspected cashew nut allergy.
Content of this journal is licensed
under a Creative Commons
Attribution-NonCommercial 4.0
International License.
Corresponding Author:
İlknur Bostancı
ilknurbirol@hotmail.com
Received: 20.05.2020
Accepted: 11.11.2020
Available Online Date: 12.01.2021
turkarchpediatr.org
ABSTRACT
Objective: The prevalence of cashew nut allergy is increasing. Clinical reaction to cashew nuts
may be severe, including anaphylaxis. In this study, we aimed to evaluate the frequency of ca-
shew nut sensitivity in a group of children with food allergy and the clinical features and course
of cashew nut allergy.
Material and Methods: A retrospective chart review was performed on 516 children who pre-
sented with food allergy at a pediatric allergy department. Individuals sensitized to cashew
nuts were examined.
Results: Cashew nut sensitization was detected in 17 (64.7% male; mean age of symptom onset,
14 months) of 516 patients with food allergy. Skin symptoms were the most frequent clinical pre-
sentation, followed by gastrointestinal symptoms. Overall, 29.4% of the patients presented with
anaphylaxis. All anaphylactic reactions were developed after the first consumption of cashew
nuts. Of the cashew nut–sensitized patients, 82.3% were diagnosed with moderate-to-severe
atopic dermatitis, and all of them had multiple food allergies. During the follow-up, 90% of the
patients who had cashew nut sensitization and co-existing food allergies to cow’s milk and/or
hen’s egg developed tolerance to cow’s milk and/or hen’s egg, but none of the patients could
tolerate cashew nut ingestion.
Conclusion: Cashew nut is a potent allergen, causing severe allergic reactions that persist long
term compared with other food allergies. Early onset of moderate-to-severe atopic dermatitis
and multiple food allergies are remarkable co-existing conditions in children who have been
diagnosed with cashew nut allergy. Pediatricians should be aware of this emerging food al-
lergy.
Keywords: Anaphylaxis, cashew nut, IgE-mediated allergy, sensitization, tree nut allergy
Cite this article as: Ertuğrul A, Bostancı İ, Özmen S. A remarkable food allergy in children: cashew nut allergy.
Turk Arch Pediatr 2021; 56(2): 131-5.
131
Introduction
Tree nut allergy aects over 2% of children (1). Recent studies on cashew nuts (CNs) suggest
that the prevalence of CN allergy is increasing with raising consumption (2). In the 2017–2018
season, CN production raised by 32% over the previous decade worldwide. The biggest ca-
shew consumers in the world are India, USA, Germany, Netherlands, and the United Kingdom
(3). Cashew nut allergy seems to have become a significant problem, not only in these places
but also in other regions, because of the increase in consumption over the past years (4).
Nuts are frequently consumed as snacks in Turkey. Sunflower seeds are the most commonly
consumed snacks, followed by mixed nuts (common constituents of mixed nuts: hazelnuts,
pistachios, almonds, walnuts, peanuts, and CNs) in the traditional eating habits of Turkey (5).
Parallel to the growing trend of CN consumption throughout the previous 10 years all over
the world, we suggest that the rate of CN sensitization is also likely to increase in Turkey as
reported in the previous studies (2).

132
Cashew nut allergy presents most commonly in the first five
years of life (range, 2 months to 27 years), with typical rap-
id-onset immunoglobulin E (IgE)-mediated symptoms (1, 2).
Clinical reaction to CNs may be severe, including anaphylaxis,
suggesting high potency comparable with other tree nuts and
peanuts (2, 6). The mainstay of therapy in CN allergy is avoid-
ance of CNs; however, this is not easy to provide in patients
with CN allergy because it exists in many food products (2). The
majority of children allergic to hen’s egg or cow’s milk often de-
velop tolerance over time, but CN allergy tends to show lifelong
persistence similar to other nuts (1).
Although CN allergy is a serious health problem in children,
it remains understudied in comparison to peanuts and needs
to be underscored as a potent food allergen. In this study, we
present the patients who were sensitized to CNs in a group of
children with food allergy attending a pediatric allergy clinic.
We assessed the clinical features and course of CN allergy.
Material and Methods
A retrospective chart review was performed on 516 children
less than 18 years of age who presented with food allergy over
a 24-month period at the pediatric allergy department of a ter-
tiary care children’s hospital. Food allergy diagnosis was based
on the combination of clear-cut history, typical clinical presen-
tation, positive skin prick test (SPT)/specific IgE, or oral food
challenge (OFC) test (7).
Skin prick test with CN was not applied to all children (n=516)
with food allergy. Among these children, those with a history
of allergic reaction to CNs and/or pistachios were evaluated
for CN allergy in the clinic, but others were not prick tested
with CNs routinely. A total of 17 patients sensitized to CNs (evi-
dence of nut-specific IgE shown by a positive SPT [Stallergenes,
France]) were recruited in the study. A positive SPT was defined
as a mean wheal diameter at least 3 mm greater than the neg-
ative control. We used the ratio defined as histamine equivalent
prick (HEP)-index diameter. We divided the average diameter
of allergen-induced wheal by the average diameter of hista-
mine-induced wheal.
Tolerance was defined for patients whose first OFC was posi-
tive and last OFC was negative during the follow-up. Anaphy-
laxis was defined according to the clinical criteria reported in
“Anaphylaxis: guidelines from the European Academy of Aller-
gy and Clinical Immunology” (8). Hannifin and Rajka criteria
were used to confirm the diagnosis of atopic dermatitis (AD)
(9). The SCORing Atopic Dermatitis (SCORAD) index is used to
assess the severity of AD. Scores below 25 were classified as
mild, scores 25–50 were classified as moderate, and scores
over 50 were classified as severe AD (10).
Ethical approval was received from Keçiören Training and Re-
search Hospital Ethics Comity (protocol number 2012-KAEK-
15/2090). The study was conducted in accordance with the
Declaration of Helsinki.
Statistical analysis
Among the descriptive statistics, continuous variables were
shown as mean and standard deviation (SD). For data not nor-
mally distributed, median with data range (minimum to max-
imum or interquartile range) was used. Categorical variables
are shown as number and percentages. The Mann-Whitney
U test was used for the comparison of continuous inter-group
values. All analyses were performed with IBM SPSS Statistics,
version 15.
Results
A total of 17 patients sensitized to CNs were recruited in the
study. Patients were diagnosed with CN allergy with the com-
bination of clear-cut history, typical clinical presentation, and
positive SPT or OFC. Patients with a history of anaphylaxis af-
ter CN ingestion (n=5) and positive SPT with CN were not chal-
lenged. Of 17 patients, four were not challenged because their
parents did not approve the OFC. All four patients had a posi-
tive SPT with CN with a wheal size greater than 10 mm, which is
the reported cuto value to predict clinical reactivity for CN (11).
Cashew nut sensitization was detected in 17 of 66 patients with
tree nut allergy. A flowchart of the patients is shown in Figure
1. Demographic and clinical characteristics of patients with CN
sensitization are shown in Table 1.
Clinical symptoms after CN intake are shown in Figure 2. Skin
symptoms were the most frequent clinical presentation, fol-
lowed by gastrointestinal symptoms. Of 17 patients, four never
consumed CNs. The parents of these four children did not ap-
prove the OFC, so they were still on an elimination diet. These
four patients had moderate-to-severe AD with multiple food
allergies, and two of them had anaphylaxis with hazelnut.
Anaphylaxis occurred in 9 of 66 patients who were diagnosed
with tree nut allergy. Of those, five were due to CN ingestion.
There was no identified biphasic reaction. None of the ana-
phylactic reactions required hospital admission longer than 24
hours.
Turk Arch Pediatr 2021; 56(2): 131-5Ertuğrul et al. Cashew nut allergy
Table 1. Demographic and clinical characteristics of children
with cashew nut sensitization
Total n (%) (N=17)
Gender
Male 11 (64.7)
Mean age (month)* 37 (11–66)
Mean age of symptom onset (month)* 14 (6–30)
Atopic disease
Atopic dermatitis 14 (82.3)
Anaphylaxis 9 (52.9)
Asthma 5 (29.4)
Sensitization of other tree nut allergy
Pistachio nut 14 (82.3)
Walnut 9 (52.9)
Hazelnut 9 (52.9)
Almond 5 (29.4)
Sensitization of peanut allergy 5 (29.4)
Co-existing food allergy
Egg 8
Cow’s milk 6
Mean total IgE (ku/L)* 309 (16–2.150)
Mean tryptase level (μg/L)* 6.7 (3.8–10.9)
*Minimum–maximum interval. IgE, immunoglobulin E.

133
Of 17 CN-sensitized children, 14 had AD. According to the
SCORAD index, all of these patients were diagnosed as mod-
erate-to-severe AD. All patients with CN sensitization had
multiple food allergies. All patients with CN sensitization had
co-existing sensitization proven by positive SPT with at least
one of the tree nuts, as described in detail in Table 1. Overall,
58.8% of patients with CN sensitization had co-existing chal-
lenge-proved food allergies with cow’s milk and/or hen’s egg.
The mean±SD wheal diameter of SPT with CN was 10.3±6.9 mm.
The mean±SD HEP-index diameter of CN was 1.4±0.85. Patients
were divided into two groups (patients with anaphylactic and
non-anaphylactic CN reactions) according to the clinical re-
actions to CN based on international anaphylaxis guidelines
(8). There was no dierence in the HEP-index diameter or SPT
mean wheal diameter between these two groups (p>0.05). No
dierences were found concerning total IgE, basal tryptase
level, and absolute eosinophil count between the two groups
(p>0.05) (Table 2).
Patients whose parents refused OFC or patients with positive
OFC continued an elimination diet during the follow-up. During
the follow-up (minimum–maximum, 6–24 months), none of the
patients were re-challenged with CN. Two patients had eat-
en CNs in the follow-up period accidentally, and IgE-mediated
clinic symptoms were observed. All of the patients with CN sen-
sitization had still been on an elimination diet. Of the patients
with CN sensitization, 35.2% developed tolerance to some of the
other tree nuts (pistachio nut, walnut, hazelnut, almond, pea-
nut) rather than CN, as shown in Figure 3. Of the patients who
had co-existing food allergies to cow’s milk and/or hen’s egg,
90% developed tolerance to cow’s milk and/or hen’s egg.
Discussion
In this study, results show that CN is causing considerably se-
vere reactions among tree nuts, and CN allergy is associated
with a significant risk of anaphylaxis in children. Most of the
children were sensitized to CN without ever consuming CNs in
the infancy period. Early onset of moderate-to-severe AD and
multiple food allergies are remarkable co-existing conditions in
children who have been diagnosed with CN allergy.
In our study, we found that 3.2% of the 516 children diagnosed
with food allergy were sensitized to CN over a 24-month peri-
od. In Sweden, over a 10-year period, the estimated prevalence
of CN allergy was 6% of food allergic children (12). We suggest
that the dierence may be due to the eating habits and fre-
quency of CN consumption in dierent geographical areas and
awareness of the doctors for the diagnosis of CN allergy. In our
study, 26% of the nut allergic patients were sensitized to CN.
Davoren et al. (6) and Moneret-Vautrin et al. (13) indicated that
12.6% and 41%, respectively, of the nut allergic patients were
sensitized to CNs.
The median age of CN reaction was about 24 months in the
literature (14). In our study, the age of onset of allergic symp-
toms to CN varies between 6 and 30 months, with a mean age
of 14 months. For CN allergy, the ingestion of CNs seems to be
the principal sensitization path, although mechanisms associ-
Turk Arch Pediatr 2021; 56(2): 131-5 Ertuğrul et al. Cashew nut allergy
Table 2. Comparison of children with CN sensitization according to the clinical reactions to CN based on anaphylaxis
Patients Patients with anaphylactic reaction Patients with non-anaphylactic reaction p
Wheal diameter of SPT with CN 20 (10.5–21.5) 6 (5–9) 0.069
Mean HEP-index diameter of CN 1.40 (1.05–1.88) 1.09 (0.88–1.42) 0.268
Total IgE (ku/L) 106 (35–1.643) 74 (38–343) 0.794
Basal tryptase level (μg/L) 8.3 (5.2–8.3) 5.2 (3.8–7.8) 0.154
Absolute eosinophil count (microL) 350 (90–500) 205 (105–487) 0.799
CN, cashew nut; HEP, histamine equivalent prick; IgE, immunoglobulin E; SPT, skin prick test.
All values reported as median (interquartile range).
Figure 1. Flowchart of the study
In 24 months 516 patients were diagnosed as food allergy
Patients with tree-nut-allergy
66/516 (13%)
Patients without tree-nut-allergy
450/516 (87%)
Sensitized with cashew nut
17/66 (26%)
Not sensitized with
cashew nut
49/66 (74%)
Figure 3. Tolerance acquisition to tree nuts in patients with cashew nut
sensitization
Cashew Pistachio Walnut Hazelnut Almond Peanut Cow’s Hen’s
nut nut milk egg
Number of patients
On elimination diet Tolerant
18
16
14
12
10
8
6
4
2
0
Figure 2. Clinical symptoms after cashew nut ingestion
Skin symptoms
(Urticaria, angioedema, redness,
itchiness, atopic dermatitis
exacerbation)
13 patients (100%)
Gastrointestinal symptoms
(Nausea, vomiting, diarrhea)
4 patients (30%)
Respiratory symptoms
(Cough, wheeze, shortness of breath)
3 patients (23%)
4/17 had
never eaten
cashew nut
17 patients with
cashew nut
sensitization

134
ated with poor skin barrier function such as AD have also been
highlighted as an increasing risk factor for the development of
CN allergy (4). Crealey et al. (15) reported that 76% of those
reacting to CNs had eczema (65% of those developing it in the
first six months of life). Compatibly, most of our patients had
moderate-to-severe AD in early life and were sensitized to CNs
without ever consuming them. Our patients’ data supported the
mechanism associated with disrupted skin barrier integrity and
transcutaneous sensitization.
Most of the reported clinical reactions to CNs are moderate to
severe, and fatalities have also been reported (5). Gastrointes-
tinal symptoms are common after skin involvement and more
frequent in comparison to peanut and other tree nut allergies
(16, 17). In this study, skin symptoms were the most common,
followed by gastrointestinal and respiratory symptoms, which
corresponds to previous reports (18). In our study group, five
of 17 patients (29.4%) sensitized with CN presented with ana-
phylactic reaction after ingestion of CNs. Anaphylactic reac-
tion was developed after the first consumption of CNs. Three
of these patients were younger than 12 months, and four of
them had a history of severe AD. Crealey et al. (15) reported
that 53% of children with clinical reaction to CNs presented
with anaphylaxis, and Clark et al. (19) reported more severe
symptoms (more bronchoconstriction and more cardiovascular
symptoms) to CNs compared with peanut allergy. Anaphylaxis
occurring without cutaneous features has previously been re-
ported, but none of our patients presented without cutaneous
features (6). The SPT’s mean wheal diameter, HEP-index di-
ameter, total IgE, basal tryptase level, and absolute eosinophil
count did not dier significantly among patients with anaphy-
lactic and non-anaphylactic CN reactions. The small number
of patients may limit the analysis. Cetinkaya et al. (20) showed
that asthma, egg white allergy, higher serum basal tryptase
levels, and female gender were independent risk factors for
anaphylaxis in children with tree nut allergies.
The cashew plant
(Anacardiumoccidantale L)
, pistachio nut
(Pistaciavera)
, and mango
(Mangiferaindica)
belong to the
Anacardiacea family, and previous studies demonstrated
cross-reactivity to CNs and pistachio (21). Of the patients with
CN sensitization, 82.3% had co-sensitization with pistachio
nut in our group. Because the consumption of mango is very
rare in Turkey, mango allergy was not evaluated. van der Valk
et al. (22) reported in their study evaluating 29 children that
co-sensitization between CNs and pistachio nuts was 98%, but
pistachio nut sensitization was clinically relevant in 34% of the
children. Unless a negative OFC is demonstrated, avoidance of
pistachio nuts must be advised. The other related tree nut aller-
gens should be investigated before avoidance (2).
There were no patients with CN allergy alone; all patients had
multiple food allergies in our study. Overall, 58.8% of our pa-
tients clinically reacted to another food with cow’s milk and/or
hen’s egg. Recent data show that early-onset severe eczema
and egg allergy is a significant risk factor for peanut allergy
(23-25). Most of our patients with CN sensitization had ear-
ly-onset moderate-to-severe eczema, and more than half of
them had hen’s egg and/or cow’s milk allergy. We propose that
not only peanut but also CN allergy is alarming for this group
of patients.
Over 36 months, all of the patients with CN sensitivity were still
on a CN elimination diet, although 90% of these patients devel-
oped clinical tolerance to cow’s milk and/or hen’s egg. During
follow-up with patients in whom OFCs were performed, there
were no patients who developed tolerance to CNs. Prevention
and detection of CN allergy in clinical practice is highly import-
ant, because this potent allergen seems to be responsible for
the long-lived allergy (1).
This study projects experiences in a tertiary allergy clinic but
has some limitations because of the retrospective composi-
tion. The most important limitation of the study was the small
number of participants. The specific IgE level of CNs was not
measured because of the insuciency of the hospital’s labora-
tory. However, in a recent study, it is indicated that SPT with CN
is more predictive than specific IgE for positive OFC (11). Oral
food challenges were not performed on the patients whose
parents did not give written informed consent. In spite of these
facts, it is a real-life study pointing to the life-threatening se-
vere reactions after CN intake in children.
Cashew nut is a potent allergen causing severe and systemic
allergic reactions that persist long term compared with other
food allergies. Cashew nut allergy is associated with a signifi-
cant risk of anaphylaxis; therefore, anaphylaxis should be con-
sidered when evaluating children with a suspected CN aller-
gy. There is a vigorous prevalence of atopy among CN allergic
subjects. Children who have a food allergy to hen’s egg and/
or cow’s milk, with early onset of moderate-to-severe AD, seem
to be at risk.
Ethical Committee Approval: Ethics committee approval was received
for this study from the ethics committee of Keçiören Training and Re-
search Hospital (2012-KAEK-15/2090).
Informed Consent: Patient consent was not obtained due to the retro-
spective design of the study.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept – A.E., İ.B., S.Ö.; Design – A.E., İ.B., S.Ö.;
Supervision – A.E., İ.B., S.Ö.; Funding – A.E., İ.B., S.Ö.; Materials – A.E.,
İ.B., S.Ö.; Data Collection and/or Processing – A.E., İ.B., S.Ö.; Analysis
and/or Interpretation – A.E., İ.B., S.Ö.; Literature Review – A.E., İ.B., S.Ö.;
Writing – A.E., İ.B., S.Ö.; Critical Review – A.E., İ.B., S.Ö.
Conflict of Interest: The authors have no conflicts of interest to de-
clare.
Financial Disclosure: The authors declared that this study has received
no financial support.
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