DISCUSSION
In this retrospective Portuguese pediatric study that included 98
patients, the most frequent nuts involved were peanut (63%), hazelnut
(59%) and walnut (53%). Mean age at first reaction was 5.8 years,
being younger in patients with peanut allergy comparing with other nuts
(4.6 years versus 6.7 years, p=0.02). We assume that it is a possible
consequence of a recent rising nuts consumption in pediatric population
in our country, predominantly of peanut. In Spain, Haroun-Díaz Eet al . reported these same three nuts (hazelnut, peanut and
walnut) as the most frequent nuts eliciting allergy.15Allergy prevalence for each TN seems to vary in different regions of the
world: hazelnut allergy is the most frequent in continental Europe;
peanut, brazil nut, walnut and almond are the most commonly reported in
the United Kingdom, and walnut and cashew allergies in the United
States. These differences are representative of the variations in nuts
consumption in each country, leading to different sensitization
patterns.8, 16,17
Most patients had history of atopy (n=86, 88%), including 44% with
eczema and 31% with egg allergy. Cetinkaya PG et al. reported a
higher frequency of these atopic conditions in patients allergic to
nuts, with 72% having atopic dermatitis and 50% egg allergy, probably
related to a higher number of involved children.18 The
epithelial barrier dysfunction characteristic of atopic dermatitis is a
confirmed risk factor for the development of allergic sensitization,
food allergy and other allergic diseases. Many epidemiological studies,
and recently also studies in animals, demonstrated the connection
between skin and digestive tract. Damaged keratinocytes produce IL-33,
that stimulates group 2 innate lymphoid cells (ILC2) in the small
intestine. These in turn produce IL-4 and IL-13, which leads to the
expansion of activated mast cells, resulting in an increment of
intestinal permeability and consequent transmission of allergens that
can trigger food allergy.19,20
Nut reactions may be severe on the first contact. About one third of our
patients presented with anaphylaxis, and more than half were
polysensitized to several nuts, which in accordance with recent data of
international cohorts.1, 18 Avoidance of all nuts has
been the rule for many years in patients allergic to one nut, but the
possible introduction of other nuts has recently been investigated in
several studies.21,22 In our study, 9 out of the 15
OFCs performed with non-culprit nuts to which patients were sensitized,
but not exposed to before, were negative, favoring the above-mentioned
idea of avoiding unnecessary nuts restrictions. Additionally, 31 (32%)
were monosensitized after allergological investigation (16 to peanut, 7
to walnut, 4 to cashew, 2 to hazelnut and 2 to pine nut).
IgE sensitization to pan-allergen LTP were the most prevalent in our
population, differently from a Spanish cohort that found the 2S albumin
family of the seed storage proteins as the most
frequent.1 It is, however, in line with recently
published Portuguese data.23
In our pediatric cohort, anaphylaxis was more common in patients with
chestnut and cashew allergies. Severe systemic reactions in patients
sensitized to cashew have been frequently reported in
Europe.9,12,14 A Portuguese study on TN anaphylaxis in
preschool age children concluded that cashew was the major culprit,
accounting for 11 of the 25 cases.24 Data on chestnut
allergy is sparce, especially considering prevalence and reaction’s
severity. Our results could be explained by Portuguese eating habits,
with chestnut being one of the most appreciated nuts, typical of the
colder months.
Allergological investigation proved to be useful in anaphylaxis risk
prediction. MPD should be valued not only for diagnosis but also for
anaphylaxis risk prediction. In our study, MPD was significantly higher
for almond, cashew and pistachio in patients with anaphylaxis to these
TNs. Other authors reported utility of ST in diagnosis prediction (MPD ≥
8mm), but not in anaphylaxis risk prediction.9,12 sIgE
did not differ significantly between groups. However, it should be taken
into account that there was limited availability of whole extract sIgE
for some of the nuts analyzed (namely cashew, pistachio, chestnut and
pine nut) and that not all patients did sIgE measurements. In addition,
as previously postulated,25,26 our study highlights
the important adding value that sIgE/total IgE ratio could bring to
clinical practice. For example, sIgE measurement for walnut was not a
good predictor of anaphylaxis but, when integrated in sIgE/total IgE
ratio, it reached statistical significance. Component-resolved diagnosis
was used as a study complement, showing interest in risk stratification,
particularly for peanut, with Ara h 2 and Ara h 6 being significantly
higher in patients with anaphylaxis, which is in line with other
reports.26
The present study has some limitations, such as the small sample of
patients, which limits extrapolation of the results, and its
retrospective design, that could itself weaken our findings. However, it
is the first Portuguese study which extensively characterizes a
pediatric population with TN and peanut allergy, analyzing the clinical
utility of ST, sIgE and mcIgE measurements and, importantly and sparsely
reported, sIgE/total IgE ratio in anaphylaxis prediction, and so the
authors believe that it could add significant value to clinical
practice.