Phenotypes of IgE-mediated food allergy in Turkish children.

Abstract

Data on food allergy-related comorbid diseases and the knowledge on factors associating specific food types with specific allergic outcomes are limited. The aim of this study was to determine the clinical spectrum of IgE-dependent food allergy and the specific food-related phenotypes in a group of children with IgE-mediated food allergy. Children diagnosed with IgE-mediated food allergy were included in a cross-sectional study. IgE-mediated food allergy was diagnosed in the presence of specific IgE or skin-prick test and a consistent and clear-cut history of food-related symptoms or positive open provocation test. Egg (57.8%), cow's milk (55.9%), hazelnut (21.9%), peanut (11.7%), walnut (7.6%), lentil (7.0%), wheat (5.7%), and beef (5.7%) were the most common food allergies in children with food allergy. The respiratory symptoms and pollen sensitization were more frequent in children with isolated tree nuts-peanut allergy compared with those with egg or milk allergy (p < 0.001); whereas atopic dermatitis was more frequent in children with isolated egg allergy compared with those with isolated cow's milk and tree nuts-peanut allergy (p < 0.001). Children with food allergy were 3.1 (p = 0.003) and 2.3 (p = 0.003) times more likely to have asthma in the presence of allergic rhinitis and tree nuts-peanut allergy, respectively. Interestingly, children with atopic dermatitis were 0.5 (p = 0.005) times less likely to have asthma. Asthma (odds ratio [OR], 2.3; p = 0.002) and having multiple food allergies (OR, 5.4; p < 0.001) were significant risk factors for anaphylaxis. The phenotypes of IgE-mediated food allergy are highly heterogeneous and some clinical phenotypes may be associated with the specific type of food and the number of food allergies.

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Phenotypes of IgE-mediated food allergy in
Turkish children
DO NOT COPY
S. Tolga Yavuz, M.D., Umit M. Sahiner, M.D., Betul Buyuktiryaki, M.D., Ozge U. Soyer, M.D.,
Ayfer Tuncer, M.D., Bulent E. Sekerel, M.D., Omer Kalayci, M.D., and Cansin Sackesen, M.D.
ABSTRACT
Data on food allergy–related comorbid diseases and the knowledge on factors associating specific food types with specific
allergic outcomes are limited. The aim of this study was to determine the clinical spectrum of IgE-dependent food allergy and
the specific food-related phenotypes in a group of children with IgE-mediated food allergy. Children diagnosed with IgE-
mediated food allergy were included in a cross-sectional study. IgE-mediated food allergy was diagnosed in the presence of
specific IgE or skin-prick test and a consistent and clear-cut history of food-related symptoms or positive open provocation test.
Egg (57.8%), cow’s milk (55.9%), hazelnut (21.9%), peanut (11.7%), walnut (7.6%), lentil (7.0%), wheat (5.7%), and beef
(5.7%) were the most common food allergies in children with food allergy. The respiratory symptoms and pollen sensitization
were more frequent in children with isolated tree nuts–peanut allergy compared with those with egg or milk allergy (p ? 0.001);
whereas atopic dermatitis was more frequent in children with isolated egg allergy compared with those with isolated cow’s milk
and tree nuts–peanut allergy (p ? 0.001). Children with food allergy were 3.1 (p ? 0.003) and 2.3 (p ? 0.003) times more
likely to have asthma in the presence of allergic rhinitis and tree nuts–peanut allergy, respectively. Interestingly, children with
atopic dermatitis were 0.5 (p ? 0.005) times less likely to have asthma. Asthma (odds ratio [OR], 2.3; p ? 0.002) and having
multiple food allergies (OR, 5.4; p ? 0.001) were significant risk factors for anaphylaxis. The phenotypes of IgE-mediated food
allergy are highly heterogeneous and some clinical phenotypes may be associated with the specific type of food and the number
of food allergies.
(Allergy Asthma Proc 32:e47–e55, 2011; doi: 10.2500/aap.2011.32.3481)
T
heterogeneity can be explained based on ethnic, nutri-
tional, and cultural differences among different popu-
lations as well as the differences in the study design
and methodology. It is generally believed that self-
reported prevalence tends to overestimate the preva-
lence of food allergy.1,3More recent studies based on
objective measures such as skin-prick tests, specific IgE
to foods, and, especially, double-blind placebo-con-
trolled food challenges (DBPCFCs) suggest that the
prevalence of food allergy ranges between 1 and
10.8%.1,2In Turkey food allergy shows a similar pat-
tern, parent-reported food allergy is 5.7% in children
aged between 6 and 9 years old; however the preva-
lence of food allergy confirmed by the DBPCFC is only
0.8%.4,5
Although there are geographical, social, and nutri-
tional differences, cow’s milk and eggs in infancy and
peanuts in older age groups are by far the most com-
he reported prevalence of food allergy shows great
variations among different populations.1,2This
mon foods causing allergic reactions in children.6,7In
recent years, prevalence of allergies to kiwi and sesame
seed has increased in some countries.8,9
In addition to providing epidemiologic data, these
studies have focused on the clinical manifestations in-
cluding anaphylaxis and on the factors that are predic-
tive of outgrowing food allergy.10–13Atopic dermatitis
with food allergy is the first manifestation of the atopic
march and asthma and allergic rhinitis appear later in
life.14The association of eczema and the development
of food allergy in infancy is documented in several
studies.15–17However, the data on food allergy–related
comorbid diseases other than atopic dermatitis such as
asthma and allergic rhinitis are limited. Similarly, there
is a gap in our knowledge on factors associating spe-
cific food types with specific allergic outcomes.
Therefore, in a cross-sectional study, we set out to
determine the clinical spectrum of IgE-dependent food
allergy and the specific food-related phenotypes in a
group of Turkish children with IgE-mediated food al-
lergy.
MATERIALS AND METHODS
Patients
Children with IgE-mediated food allergy who have
been followed at the Pediatric Allergy and Asthma
Unit, Hacettepe University School of Medicine, be-
From the Pediatric Allergy and Asthma Unit, Hacettepe University, School of Med-
icine, Ankara, Turkey
The authors have no conflicts of interest to declare pertaining to this article
Address correspondence and reprint requests to Cansin Sackesen, M.D., Pediatric
Allergy and Asthma Unit, Hacettepe University, School of Medicine, 06100 Ankara,
Turkey
E-mail address: csackesen@yahoo.com
Copyright © 2011, OceanSide Publications, Inc., U.S.A.
Allergy and Asthma Proceedingse47

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tween January 2002 and May 2009 are the subjects of
this study. All children and their parents were inter-
viewed and their demographic variables and physical
examination findings were recorded. Special effort was
given to determine a cause-and-effect relationship be-
tween the ingestion of a certain food and development
of symptoms.
Children were diagnosed as having IgE-mediated
food allergy when they fulfilled both of the following
criteria18,19:
DO NOT COPY
1. Presence of specific IgE to at least one type of food
as shown by elevated titers of specific IgE (?0.35
kU/L) or positive skin-prick test.
2. A consistent and clear-cut history of food-related
symptoms that developed in early phase after the
ingestion of a certain food or positive open food
challenge.
Children without a clear-cut history of food-related
symptoms had undergone an open food challenge test.
In children allergic to more than one food, children had
a clear history of food-related symptoms after con-
sumption of each food along with specific IgE positiv-
ity.
All study procedures were performed in accordance
with a protocol previously approved by the Ethics
Committee of Hacettepe University. All parents pro-
vided written informed consent for the study proce-
dures.
Study Measurements
Skin-prick tests were performed in all patients. In
children ?2years of age, a small panel including cow’s
milk, egg, wheat, peanut, walnut, hazelnut, sesame,
soy, and lentil was performed. In children ?2 years of
age, a battery of 33 food allergens including cow’s
milk, egg, peanut, walnut, soy, wheat, hazelnut, wal-
nut, pistachio, beef, fish, lentil (red and green), chick
pea, sesame seed, pea, corn, garlic, tomato, rice, kiwi,
carrot, celery, melon, banana, apple, cumin, chicken,
green beans, red capsicum, monilia, sunflower seed,
and potato were tested (Alyostal ST-IR; Stallergenes
SA, Antony, France) on the back of the children. Prick-
to-prick testing with fresh unprocessed food was done
for peaches and lettuce to the children with a history of
symptoms after these foods. Reactions with wheals 3
mm greater than negative control were considered pos-
itive. For patients ?2 years old, skin-prick testing was
performed with an additional panel of 30 aeroallergens
including tree, grass, and weed pollens; Dermatophagoi-
des farinae; Dermatophagoides pteronyssinus; cat, dog, and
horse dander; and molds on a separate day.
Total IgE levels and specific IgE to foods were mea-
sured in sera with Uni-Cap technology in accordance
with the specifications of the manufacturer (Pharma-
cia, Uppsala, Sweden). Food-specific IgE concentra-
tions of ?0.35 kU/L were considered positive.
Eosinophil counts were determined from a Coulter
Counter (Beckman Coulter, Fullerton, CA) leukocyte
measurements.
Diagnosis of Atopic Dermatitis
Atopic dermatitis is clinically defined by the pres-
ence of pruritus and a relapsing eczematous rash typ-
ically found over flexor surfaces.20In children with
atopic dermatitis, skin symptoms significantly dimin-
ished after elimination of incriminated food.
Diagnosis of Asthma
In children capable of doing spirometry, asthma was
diagnosed in the presence of reversible airway obstruc-
tion as defined by at least a 12% improvement in forced
expiratory volume in 1 second after bronchodilator
administration21or improvement in asthma symptoms
after inhaled steroid or leukotriene modifier agent
therapy. In younger children who could not cooperate
with spirometry, asthma was diagnosed by a history of
recurrent wheezing and/or cough and a favorable
therapeutic response to antiasthma treatment.22
Diagnosis of Anaphylaxis
Diagnosis of anaphylaxis was made according to the
previously published reports.23–25Clinically, anaphy-
laxis was defined as a severe, systemic syndrome in-
volving cutaneous, respiratory, and/or cardiovascular
symptoms and/or signs, such as stridor, wheezing, or
hypotension after ingestion of implicated food.
Diagnosis of Allergic Rhinitis
Allergic rhinitis is clinically defined by occurrence of
symptoms such as rhinorrhea, nasal obstruction, nasal
itching, and sneezing in children with aeroallergen
sensitivity.26
Pediatric allergy specialists made diagnoses of ac-
companying diseases.
Statistical Analysis
Statistical analyses were performed with SPSS 15.0
for Windows (IBM SPSS Statistics, Chicago, IL). All
data including age, age of onset of symptoms, eosino-
phil counts, total IgE showing nonnormal distribution,
and the data were given as median and interquartile
range, and all statistical comparisons were performed
using Mann-Whitney U test or ANOVA on ranks as
appropriate. A value of p ? 0.05 was considered sig-
nificant for all analyses.
We have performed both univariate and multivariate
logistic regression analyses to establish the factors that
were associated with asthma and anaphylaxis. In this
model, age, age of onset of symptoms, gender, family
e48 November–December 2011, Vol. 32, No. 6

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history of allergy, atopic dermatitis, allergic rhinitis,
specific food allergies that are present in ?5% of the
studied population (cow’s milk, egg, tree nuts, peanut,
lentil, beef, and wheat), presence of inhalant allergies,
presence of multiple food allergies, eosinophil counts,
and total IgE were examined in the univariate model.
The factors that were significant in the univariate re-
gression analysis or resulted in a shift in the odds ratio
(OR; of ?0.2) for the relationship were then included as
covariates in the multiple regression analysis.
RESULTS
Three hundred fifteen children aged between 1.2
months and 19 years who fulfilled the criteria for IgE-
mediated food allergy were included in the study (Table 1).
All children had evidence of specific IgE either by skin-
prick tests or serum-specific IgE. In 189 children (60%)
there was a consistent and clear-cut history relating a
specific food type with symptoms and, moreover, 82
(26%) children had a history of anaphylaxis after the
incriminating food exposure whereas in the remaining
126 (40%) children, an open challenge test was necessary
to confirm the diagnosis of IgE-mediated food allergy.
The majority of the children presented with cutaneous
symptoms (94%; eczema, urticaria, and angioedema) fol-
lowed by respiratory symptoms (30.2%; wheezing, dys-
pnea, rhinitis, cyanosis, and hoarseness), gastrointestinal
symptoms (19.4%; oral pruritus, nausea, vomiting, ab-
dominal cramping, and diarrhea), neurological symp-
toms (2.9%; dizziness, headache, and confusion), and car-
diovascular symptoms (1.3%; hypotension, tachycardia,
and bradycardia).
Implicated Food
Frequency of various food allergies is given in
Fig. 1, A and B. There was a striking difference in the
offending food between the children whose symptoms
began before (n ? 249) and after 1 year of age (n ? 66).
Egg and cow’s milk were by far the most common food
allergies in children ?1 year of age and hazelnut, pea-
nut, and walnut were the most common in children ?1
year of age (Fig. 1 C). Interestingly, the prevalence of
lentil allergy (7%) was higher than other relatively
more commonly reported causes such as wheat
(5.7%) and soy (3.8). Similarly, the prevalence of
allergy to sesame was equal to soy (3.8%) and higher
than fish (3.2%).
Food Type and Comorbid Conditions
To see whether there is any relationship between the
offending food and the clinical presentation, we ana-
lyzed isolated cases of three most common food aller-
gies, viz., cases with isolated allergies to cow’s milk,
egg, or tree nuts–peanut. The children with hazelnut,
peanut, walnut, and pistachio were pooled together.
The age of onset of symptoms and total IgE were
significantly higher (p ? 0.001 and p ? 0.001, respec-
tively); and respiratory symptoms were more frequent
in children with isolated tree nuts–peanut allergy (p ?
0.001; Table 2). On the other hand, atopic dermatitis
was significantly more frequent in children with iso-
lated egg allergy compared with isolated cow’s milk
and tree nuts–peanut allergy (p ? 0.001; Fig. 2).
Children with food allergy were 3.1 (OR, 3.12; 95%
CI,1.49–6.53; p ? 0.003) and 2.3 (OR, 2.34; 95% CI,
1.33–4.12; p ? 0.003) times more likely to have asthma
in the presence of allergic rhinitis and tree nuts–peanut
allergy, respectively. Interestingly, children with atopic
dermatitis were 0.5 (OR, 0.48; 95% CI, 0.29–0.80; p ?
0.005) times less likely to have asthma (Table E1; sup-
plementary material).
Aeroallergen Sensitization
Pollen sensitization was significantly more frequent
in children with tree nuts–peanut (55.6%) allergy than
in children with cow’s milk allergy (3.1%) and egg
allergy (3.6%; p ? 0.001; Fig. 3). Interestingly, there was
no house-dust mite sensitization among children with
tree nuts–peanut allergy.
Table 1 Characteristics of the patients with food
allergy (n ? 315)
DO NOT COPY
Age (current)
Gender (male/female)
Age of onset of
symptoms (yr)
Family history of allergy,
n (%)
Presenting symptoms, n (%)
Skin
Respiratory
Gastrointestinal
Neurological
Cardiovascular
Eosinophils/mm3
Total IgE (kU/L)
Patients with two or more
food allergies, n (%)
Concomitant atopic
dermatitis
Concomitant asthma
Concomitant allergic rhinitis
Aeroallergen sensitivity
House-dust mite
Pollen
Cat dander
*Median (interquartile range).
4.82 (2.1–8.2)*
220 (69.8%)/95 (30.2%)
0.5 (0.3–0.7)*
127 (40.3)
296 (94.0)
95 (30.2)
61 (19.4)
9 (2.9)
4 (1.3)
500 (296–863)*
118 (46–304)*
159 (50.5)
191 (60.6%)
104 (33.0%)
38 (12.1%)
14 (4.4%)
42 (13.3%)
10 (3.2%)
Allergy and Asthma Proceedingse49

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Mono versus Multiple Food Allergies
One hundred fifty-nine children (50.5%) were multi-
sensitized and 156 children (49.5%) were monosensi-
tized. Children with multiple food allergies had a
higher rate of positive family history, allergic rhinitis,
and atopic dermatitis and higher eosinophil counts and
plasma concentration of total IgE than monosensitized
children (Table 3).
Anaphylaxis
Of the 315 children, 129 (40.9%) had acute anaphy-
lactic reactions. Offending foods were cow’s milk
(62%), egg (45.7%), tree nuts–peanut (30.2%), meat
(9.3%), lentil (7.6%), fish (5%), wheat (4.7%), and
soy (4.7%). Multivariate logistic regression analysis
showed that asthma (OR, 2.32; 95% CI, 1.35–3.97; p ?
0.002) and having multiple food allergies (OR, 5.43;
95% CI, 2.79–10.61; p ? 0.001) were significant risk
factors for anaphylaxis (Table E2; supplementary ma-
terial).
DISCUSSION
Our study shows that the type of offending food has
significant influences on the targeted organs and asso-
ciated allergic disease. Children with isolated egg al-
lergy have a lower rate of respiratory allergies,
whereas children with tree nuts–peanut allergy have a
higher rate of pollen but not dust-mite sensitization
and a higher rate of asthma. The data also suggest that
multisensitized children have a more severe clinical
presentation including higher risk of anaphylaxis.
The spectrum of food allergies varies greatly accord-
ing to the geographical location and related dietary
habits. In the United States, the most frequent food
A.
57.8
55.9
60
80
100
21.9
11.7
7.6
7
5.7 5.7
0
20
40
%
B.
6.0
8.0
10.0
%%
3.8 3.8
3.2
2.5
1.9 1.91.61.3 1.3 1.3
11
0.60.3 0.3 0.3 0.3
0.0
2.0
4.0
CC.
66.3
69.9
42.4
50
60
70
80
<1 year (n=249)
≥1 year (n=66)
Onset of allergic symptoms
3
4.4
4.8
5.6
6.4
6.8
16.5
10.6
18.2
12.1
30.3
16.7
12.1
00
10
20
30
40
%
Figure 1. Frequency of food allergens in children with
IgE-mediated food allergy. (A) The most frequent food
allergens. (B) Uncommon food allergens responsible
for symptoms induced by food intake. (C) The most
frequent food allergens in children younger and older
than 1 year of age.
e50November–December 2011, Vol. 32, No. 6
DO NOT COPY

Page 5

allergens in young children are cow’s milk, egg, pea-
nut, wheat, soy, tree nuts, fish, and shellfish,18whereas
in the Mediterranean area some legumes and sesame
seed are among the more frequent food allergies.27–29
Compared with other regions, sesame seed allergy is
more frequent in Israel and lentil allergy is more com-
mon in Spain.9,28Our study shows that lentil allergy
also emerges as a common cause in Turkey. According
to 2007 Food and Agriculture Organization reports,30
India (36%), Canada (17%), and Turkey (15%) are ma-
jor producers of lentil in the world. Traditionally, and
probably because of its high production, lentil is intro-
duced into the diet early in life, which may be respon-
sible for the relatively higher frequency of lentil allergy
in the Turkish population (7%). Similarly, sesame has a
frequency equal to that of soy and higher than fish.
This may also account for high levels of sesame in the
Turkish diet.
Our study shows that hazelnut, but not peanut, is
one of the major food allergens in Turkish children.
Turkey is the major producer of hazelnut and provides
77% of the world’s production.31Hazelnut consump-
tion is therefore very high in Turkey and replaces
peanuts in the United States in this regard.
Roughly, 50% of the children in our study had mul-
tiple food allergies. This observation supports previ-
ous reports that have shown that a significant por-
tion of food-allergic children have multiple food
allergies.10,11,27,32–34
In our cohort, children with multiple food allergies
had a more severe atopic phenotype as evidenced by
higher total IgE response; higher eosinophil counts;
and higher rates of atopic dermatitis, allergic rhinitis,
and anaphylaxis but not asthma. Although the mech-
anism of this association is not clear, it definitely indi-
cates that children with multiple food allergies need to
76.4
8080
90
100
isolated egg
p=0.001100 . 0<p100 . 0<p
23 6 23.6
35.4
29.2
51.9
63
37
40
50
60
70
%
isolated cow’s milk
isolated tree nuts & peanut
3.6 3.1
0
10
20
30
Atopic dermatitis Bronchial asthmaAllergic rhinitis
Figure 2. The frequency of atopic dermatitis, asthma,
and allergic rhinitis in children with isolated egg al-
lergy, isolated cow’s milk allergy, and isolated tree
nuts and peanut allergy.
Table 2 Comparison of the characteristics in children with isolated cow’s milk, egg, and tree
nuts–peanut allergies
DO NOT COPY
Isolated Cow’s Milk
(n ? 65)
Isolated Egg
(n ? 55)
Isolated Tree Nuts–Peanut
(n ? 27)
p
Age of onset (yr)*
Gender
Male
Female
Family history of allergy
Eosinophils/mm3*
Total IgE*
Presentation symptoms (%)
Skin
Respiratory
Gastrointestinal
*Median (interquartile range).
#Kruskal-Wallis test.
§?2-test.
¶Comparison between three groups were adjusted for age of onset of food allergy.
0.4 (0.0.5)0.4 (0.0.5)1.5 (1.3.0)
?0.001#
41 (63.1%)
24 (36.9%)
33.8%
487 (28657)
96.5 (51.7–181)
34 (61.8%)
21 (38.2%)
30.9%
500 (230–858)
66.4 (26.5–170)
22 (81.5%)
5 (18.5%)
55.6%
300 (176–522)
256 (83.5–558)
NS§
NS§
NS#
0.007#¶
90.8
29.2
21.0
96.4
7.3
7.3
85.2
51.9
14.8
NS§
?0.001§
NS§
Allergy and Asthma Proceedingse51

Page 6

be closely followed regarding the comorbid conditions
with these more severe phenotypes, especially anaphy-
laxis.
The results of the logistic regression analysis sup-
ported the comparison between children with mono-
and multisensitizations and showed that the presence
of multiple food allergies is strongly and indepen-
dently associated with anaphylaxis (OR, 5.43; 95% CI,
2.79–10.61; p ? 0.001). In this regard, the association
was much stronger than it is with asthma (OR, 1.16;
95% CI, 0.72–1.85; p ? 0.05), although multiple allergies
are well known to be associated with asthma.35–37
Another interesting finding in the multivariate logis-
tic regression analysis was that atopic dermatitis and
egg allergy were independently associated with a de-
creased risk of anaphylaxis. Atopic dermatitis, in ad-
dition to being associated with a lower risk of anaphy-
laxis, was also associated with a lower rate of asthma,
whereas allergic rhinitis and tree nuts and peanut al-
lergy were associated with a higher rate. The associa-
tions that we observed between atopic dermatitis,
asthma, and anaphylaxis are rather unexpected. Many
reports have shown that atopic dermatitis is associated
with increased rate of asthma.14,38,39However, it
should be noted that our observation is only valid for
this specific group of children with IgE-mediated food
allergy and therefore can not be extended to a general
population. This observation needs to be confirmed in
other populations and further investigated. Our study
was not designed to offer a mechanistic explanation for
this observation.
The presence of 156 monosensitized children al-
lowed us to determine if there are any distinguishing
clinical characteristics specific for the offending food.
In parallel with the findings of Wood et al.,10the chil-
dren with isolated egg allergy showed a high incidence
of atopic dermatitis and remarkably less involvement
of the respiratory and gastrointestinal system com-
pared with children with isolated milk or isolated tree
nuts–peanut allergy in our study. Although age may
obviously be a factor underlying the difference be-
tween the higher frequencies of respiratory involve-
ment in children with tree nuts and/or peanut allergy,
it can not account for the differences observed between
the children with milk and egg allergy. Although the
age of onset is similar in children with egg and milk
allergy, respiratory and gastrointestinal involvements
are much less common in children with egg allergy.
These data suggest that the type of offending food may
Table E1 Logistic regression analysis for asthma in children with food allergy
DO NOT COPY
Univariate AnalysisMultivariate Analysis
OR
p
OR
p
Age of onset (yr)
Gender
Allergic rhinitis
Atopic dermatitis
Cow’s milk allergy
Egg allergy
Wheat allergy
Beef allergy
Lentil allergy
Tree nuts–peanut allergy
Pollen sensitization
House-dust mite sensitization
Family history
IgE
Eosinophil count
More than one food allergy
1.10 (0.98–1.23)
0.64 (0.37–1.08)
4.22 (2.08–8.57)
0.52 (0.32–0.84)
0.70 (0.44–1.12)
0.52 (0.32–0.84)
1.31 (0.49–3.49)
2.69 (1.02–7.02)
2.15 (0.90–5.14)
2.41 (1.43–4.07)
2.87 (1.48–5.56)
2.10 (0.72–6.16)
1.54 (0.97–2.45)
1.00 (1.00–1.01)
0.99 (0.99–1.00)
1.15 (0.72–1.85)
NS
NS
?0.001
0.007
NS
0.007
NS
0.044
NS
0.001
0.002
NS
NS
0.047
0.022
NS
3.12 (1.49–6.53)
0.48 (0.29–0.80)
0.003
0.005
2.34 (1.33–4.12) 0.003
55.6
60
70
80
90
100
isolated egg
isolated cow’s milk
isolated tree nuts & peanut
p<0.001 NS
3.6 3.6
3.1
4.6
0
10
0
20
30
40
50
%
Pollen
sensitization
House dust mite
sensitization
Figure 3. The frequency of pollen and house-dust mite sensitiza-
tion in children with isolated egg allergy, isolated cow’s milk
allergy, and isolated tree nuts and peanut allergy.
e52November–December 2011, Vol. 32, No. 6

Page 7

be a determinant of the targeted organ. However, the
underlying pathological mechanisms remain to be dis-
covered.
In contrast to egg, the target organ for children with
tree nuts–peanut allergies was more commonly the
respiratory system. Several studies have shown that
allergies to tree nuts and peanuts are associated with
asthma and sensitization to inhalant allergens.32,35,40,41
In our cohort, children with tree nuts or peanut allergy
had a high rate of grass pollen sensitivity. As shown by
many studies, house-dust mite sensitivity is at least as
common as pollen sensitivity in this age group.42
Therefore, this association between tree nuts or peanut
allergy and pollen sensitization is unlikely to be caused
by an epiphenomenon related to the higher frequencies
of tree nuts, peanut allergy, and pollen sensitization in
older children. A more likely explanation would be the
cross-reactivity between peanut and grass pollen aller-
gens, as has been shown by some studies.43,44
Our study has several limitations. First, the popula-
tion of this study is an extremely selected one, com-
prised of children with IgE-mediated food allergy that
presented to or were referred to a tertiary care univer-
sity clinic and therefore does not reflect on the general
Table 3 Comparison of the characteristics in children with one food allergy and more than one food allergy
Allergy to One
Food Antigen
DO NOT COPY
Allergies to More
Than One Food Antigen
p
n (%)
Age of onset* (yr)
Family history of allergic disease (%)
Presentation symptoms (%)
Skin
Respiratory
Gastrointestinal
Asthma (%)
Allergic rhinitis (%)
Atopic dermatitis (%)
Total IgE* (kU/L)
Eosinophils/mm3*
*Median (interquartile ranges).
#Kruskal-Wallis test.
§?2-test.
156 (49.5)
0.5 (0.3–0.9)
32.1
159 (50.5)
0.5 (0.3–0.6)
48.4
NS#
0.003§
91.0
23.7
15.4
31.4
8.3
47.4
94 (43.6–192.8)
452 (265–700)
96.9
36.5
23.3
34.6
15.7
73.6
0.030§
0.014§
NS§
NS§
0.044§
?0.001§
0.001#
0.011#
153.0 (56.5–462.5)
596 (304–982)
Table E2 Logistic regression analysis for anaphylaxis in children with food allergy
Univariate AnalysisMultivariate Analysis
OR
p
OR
p
Age of onset (yr)
Gender
Asthma
Allergic rhinitis
Atopic dermatitis
Cow’s milk allergy
Egg allergy
Wheat allergy
Beef allergy
Lentil allergy
Tree nuts–peanut allergy
Family history
IgE
Eosinophil count
More than one food allergy
1.08 (0.97–1.22)
0.95 (0.58–1.54)
3.59 (2.20–5.87)
2.47 (1.33–4.95)
0.31 (0.19–0.49)
1.53 (0.97–2.41)
0.43 (0.27–0.68)
0.70 (0.26–1.93)
3.06 (1.12–8.38)
0.99 (0.40–2.45)
1.49 (0.89–2.47)
1.54 (0.97–2.45)
1.00 (1.00–1.01)
0.99 (0.99–1.00)
1.88 (1.19–2.96)
NS
NS
?0.001
0.011
?0.001
NS
?0.001
NS
0.03
NS
NS
NS
NS
0.004
0.007
2.32 (1.35–3.97)0.002
0.36 (0.20–0.65) 0.001
0.36 (0.18–0.69)0.002
5.44 (2.79–10.61)
?0.001
Allergy and Asthma Proceedingse53

Page 8

population. Second, the children have had a pretty
short duration of follow-up with a median of only 1.9
years (0.8–3.6 years) in our clinic. A longer follow-up
would probably increase the percentage of asthma and
allergic rhinitis in this population and thus may change
the associations. In addition, this relatively shorter du-
ration does not allow us to determine the factors that
are associated with outgrowing food allergy. Third,
and most importantly, the diagnosis of food allergy
was not based on DBPCFCs, which is the golden stan-
dard for the diagnosis of food allergy. However, we
believe that the presence of a clear-cut history or pos-
itive open challenge, together with demonstration of
the specific IgE either by skin testing or serological
testing, leaves little doubt on the diagnosis of IgE-
mediated food allergy in the majority of cases in a
clinical setting.
In summary, this cross-sectional study shows that
phenotypes of IgE-mediated food allergy is highly het-
erogeneous and the characteristics of food allergies
including type of food allergen and the number of food
allergies may be potential confounding factors for cer-
tain clinical phenotypes.
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