INTRODUCTION
Tree nut allergies are a significant public health concern due to their potential to cause severe reactions ranging from skin rashes, atopic dermatitis, allergic rhinitis, and asthma to life-threatening conditions such as anaphylaxis. Tree nuts account for 18–40% of all anaphylaxis cases and are responsible for 70–90% of anaphylactic deaths caused by food allergies, with peanuts being the most common culprit [1, 2]. Studies conducted globally, particularly in the United States, Europe, and Australia, have shown an increase in the prevalence of tree nut allergies [3, 4]. The clinical features of tree nut allergies typically manifest shortly after exposure and include skin reactions (urticaria, angioedema), gastrointestinal symptoms (abdominal pain, vomiting), respiratory symptoms (rhinitis, asthma), and in severe cases, anaphylaxis [5]. Specific IgE levels, skin tests, and oral food challenges are utilized to support the diagnosis of tree nut allergies [6].
Tree nut allergies typically do not resolve quickly and may persist into later life, or even throughout a person’s lifetime [7]. Avoidance of the allergenic substance is the primary approach in managing these allergies [7]. While initial recommendations involve avoiding the allergen, food immunotherapy may be employed when necessary [8]. Unfortunately, only about 10% of nut allergies fully resolve [9]. However, early introduction of peanuts has been shown to significantly reduce the risk of developing peanut allergies and has modulated the immune response to peanuts [10].
AIM
This study aims to retrospectively evaluate the clinical characteristics of children aged 0–5 years with tree nut sensitivities and contribute to the existing literature.
MATERIAL AND METHODS
This is a retrospective, descriptive study. All patients aged 0–5 years diagnosed with tree nut sensitivity in our clinic over a 2-year period were included in the study.
MEASURES
The clinical features, including age, gender, allergic disease clinic (urticaria, atopic dermatitis, gastrointestinal symptoms, asthma, allergic rhinitis, anaphylaxis), total IgE, eosinophil count, specific IgE levels, and skin prick tests, of patients who presented to the Pediatric Allergy and Immunology outpatient clinic between May 2022 and May 2024 and were diagnosed with tree nut sensitivity were retrospectively evaluated using hospital database records.
We utilized ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden) for allergen specific IgE measurements. Specific IgE levels for hazelnut, peanut, walnut, pistachio, almond, cow’s milk, egg, house dust mites, cat dander, and pollen were assessed. A specific IgE level of 0.35 kU/l or higher was classified as positive. Skin prick tests were conducted using hazelnut, peanut, walnut, pistachio, almond, cow’s milk, egg, house dust mites, cat dander, and pollen. Antihistamine medication was discontinued 10 days prior to testing with histamine (10 mg/ml) serving as the positive control and saline as the negative control. A test result showing induration of 3 mm or more, in the absence of induration or dermographism in the negative control, was considered positive.
STATISTICAL ANALYSIS
The statistical analyses and data recording were performed using the software SPSS Statistics 29.0. Descriptive data in the study were expressed using medians, minimum and maximum values, as well as numbers (n) and percentages (%). The conformity of continuous variables to a normal distribution was assessed using visual (histograms and probability graphs) and analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk tests). The Mann-Whitney U test was used to compare numerical data between two groups when the data did not follow a normal distribution. The χ2 test was used for the statistical comparison of categorical variables. A p-value of < 0.05 was considered statistically significant.
RESULTS
A total of 229 children with tree nut sensitivities were evaluated in this study. The median age of the patients was 10 months, with a minimum age of 1 month and a maximum age of 59 months. 67.7% of the patients (n = 155) were male. Sensitivity to a single tree nut was observed in 52.0% (n = 119) of the patients, while 48% (n = 110) had sensitivities to multiple tree nuts. Sensitivities were as follows: hazelnut in 71.2% (n = 163), peanut in 56.3% (n = 129), walnut in 20.5% (n = 47), pistachio in 13.1% (n = 30), and almond in 13.1% (n = 30) of the patients (Table 1).
TABLE 1
Tree nuts and accompanying food and aeroallergen sensitivities of patients
| Parameter | N | % | |
|---|---|---|---|
| Nuts | |||
| Hazelnut | 163 | 71.2 | |
| Peanut | 129 | 56.3 | |
| Walnut | 47 | 20.5 | |
| Pistachio | 30 | 13.1 | |
| Almond | 30 | 13.1 | |
| Multiple nuts | 110 | 48.0 | |
| Food | |||
| Egg | 137 | 59.8 | |
| Milk | 36 | 15.7 | |
| Aeroallergens | |||
| House dust mite | 52 | 22.7 | |
| Pollen | 24 | 10.5 | |
| Cat dander | 23 | 10.0 | |
When examining other food sensitivities associated with tree nut sensitivity, egg sensitivity was present in 59.8% (n = 137) and milk sensitivity in 15.7% (n = 36) of the patients. Aeroallergen sensitivities included house dust mite in 22.7% (n = 52), pollen in 10.5% (n = 24), and cat dander in 10.0% (n = 23) of the patients (Table 1).
In 33.2% (n = 76) of the patients, atopic dermatitis was observed, while 16.7% (n = 37) had respiratory symptoms, 9.6% (n = 22) experienced anaphylaxis, 9.6% (n = 22) had gastrointestinal symptoms, and 5.2% (n = 12) presented with urticaria (Table 2).
TABLE 2
Clinical characteristics of patients
| Clinical feature | N | % |
|---|---|---|
| Atopic dermatitis | 76 | 33.2 |
| Respiratory symptoms | 37 | 16.2 |
| Anaphylaxis | 22 | 9.6 |
| Gastrointestinal symptoms | 22 | 9.6 |
| Urticaria | 12 | 5.2 |
The median eosinophil count was 420.0 × 103/µl (range: 0.0–2860.0), the median eosinophil percentage was 4.3% (range: 0.0–26.4%), and the median total IgE level was 149.0 IU/ml (range: 1.0–5585.0).
Multiple tree nut sensitivities were observed in 48.0% of the patients (n = 110). Laboratory characteristics were compared between patients with and without multiple tree nut sensitivities. The median IgE level was significantly higher in patients with multiple tree nut sensitivities (p < 0.001). However, no significant relationship was found between age, eosinophil levels, and the presence of multiple tree nut sensitivities (p > 0.05) (Table 3).
TABLE 3
Relationship between multiple nut allergy and age/laboratory parameters
The clinical characteristics of patients with and without multiple tree nut sensitivities were compared. The percentage of patients with gastrointestinal symptoms and anaphylaxis was significantly higher in those with multiple tree nut sensitivities (p < 0.047). However, there was no significant association between the presence of multiple tree nut sensitivities and the occurrence of atopic dermatitis, respiratory symptoms, or urticaria (p > 0.05) (Table 4).
TABLE 4
Relationship between multiple nut allergy and clinical features
| Parameter | Multiple nut allergy | P-value | |||
|---|---|---|---|---|---|
| No | Yes | ||||
| n | % | n | % | ||
| Atopic dermatitis | 45 | 37.8 | 31 | 28.2 | 0.122 |
| Respiratory symptoms | 17 | 14.3 | 20 | 18.2 | 0.424 |
| Anaphylaxis | 7 | 5.9 | 15 | 13.6 | 0.047 |
| GIS symptoms | 7 | 5.9 | 15 | 13.6 | 0.047 |
| Urticaria | 8 | 6.7 | 4 | 3.6 | 0.295 |
Among patients with multiple tree nut sensitivities, atopic dermatitis was observed in 28.2%, respiratory symptoms 18.2%, anaphylaxis 13.6%, and urticaria 3.4%. Among those with single sensitivities, for peanut sensitivity, atopic dermatitis was observed in 10.0%, respiratory symptoms 18.6%, anaphylaxis 1.5%, and urticaria 1.5%. For hazelnut sensitivity, atopic dermatitis was observed in 15.9%, respiratory symptoms 5.5%, anaphylaxis 1.2%, and urticaria 0.6%. No clinical symptoms were observed in almond, walnut, or pistachio sensitivity.
DISCUSSION
In this study, tree nut sensitivities were evaluated in 229 children. The average age was 10 months, and 67.7% of the patients (n = 155) were male.
Among the included patients, 52.0% (n = 119) had a sensitivity to a single type of tree nut, while 48.0% (n = 110) had multiple tree nut sensitivities. Another study reported that 36.7% (n = 76) of patients had multiple tree nut sensitivities [11]. The higher percentage of multiple tree nut sensitivities observed in our study might be related to the immune system developing sensitivity to multiple tree nut types at an early age. The higher prevalence of multiple tree nut sensitivities in our study (48%) compared to the previously reported prevalence (36.7%) could be influenced by the broader allergic profile of the studied population and regional geographic, genetic, and demographic factors.
Patients with multiple tree nut sensitivities most frequently presented with atopic dermatitis (28.2%, n = 31) and respiratory symptoms (18.2%, n = 20). Another study also identified atopic dermatitis as the most common accompanying condition [11]. These findings are consistent with previous research indicating a strong association between atopic dermatitis, respiratory symptoms, and tree nut sensitivity.
In our study, tree nut sensitivity was found as follows: 71.2% (n = 163) to hazelnuts, 56.3% (n = 129) to peanuts, 20.5% (n = 47) to walnuts, 13.1% (n = 30) to pistachios, and 13.1% (n = 30) to almonds. Hazelnuts and peanuts were the most common sensitivities, while studies conducted in European countries highlight hazelnuts and chestnuts [12]. Our study’s findings correlate with studies conducted in Europe, with hazelnut sensitivity being identified as the most common cause of multiple tree nut sensitivities.
A study has indicated that multiple food sensitivities are a risk factor for anaphylaxis [11]. In our study, the percentage of anaphylaxis and gastrointestinal symptoms was significantly higher in patients with multiple tree nut sensitivities (p < 0.047). This suggests that children with multiple tree nut sensitivities may experience more severe clinical outcomes and highlights the need for careful monitoring and the development of appropriate treatment strategies. However, more extensive studies are needed to better understand the relationship between multiple tree nut sensitivities and these clinical manifestations.
When examining food sensitivities, 59.8% (n = 137) of patients had an egg sensitivity, and 15.7% (n = 36) had a milk sensitivity. In another study from our country, 41.4% of patients had an egg sensitivity, and 28.1% had a milk sensitivity [13]. These data suggest that egg sensitivity is a common issue among children, and the high prevalence in our study may be due to the more severe allergic profile of the patient group. The high prevalence of egg sensitivity supports its status as one of the most common food sensitivities in childhood, while the relatively low rate of milk sensitivity may depend on the characteristics of the patient population, geographic factors, or dietary habits.
In our study, the median total IgE level in patients with multiple tree nut sensitivities was 273.5 (n = 110), compared to 79 in those without multiple tree nut sensitivities (n = 119). A significant increase in total IgE levels was observed in patients with multiple tree nut sensitivities (p < 0.001). Although there are limited studies in Türkiye and abroad, a study from the Ankara region reported a median total IgE level of 258 (n = 76) in patients with multiple tree nut sensitivities and 138 (n = 52) in those with single food sensitivities (p = 0.406) [13]. The significantly higher IgE levels in children with multiple tree nut sensitivities in our study suggest that this group may have a more robust immune response and higher sensitivity to allergens. This finding indicates that patients with multiple allergen sensitivities may exhibit a more aggressive allergic profile and should be monitored more closely. Despite the limited number of studies, this finding appears consistent with other research.
Regarding aeroallergen sensitivities accompanying tree nut sensitivities, sensitivity rates to dust mites, pollen, and cat allergens were found to be 22.7%, 10.5%, and 10.0%, respectively. These findings indicate that a significant portion of patients are sensitive to dust mites, suggesting that indoor allergens may be an important risk factor in children. In contrast, another study found sensitivity rates of 29.7% to pollen, 6.3% to dust mites, and 5.5% to cat dander [13]. The high prevalence of pollen sensitivity is often associated with seasonal allergies, but these differences between studies may reflect the impact of environmental factors on allergen profiles in different geographic regions.
Limitations of the study. Since our study focuses on the 0–5 age range, the results may be limited. Given the young age of our patients, the follow-up periods may not be sufficient for development of tolerance. An observational prospective study with a longer follow-up period could yield better results.
CONCLUSIONS
Our study highlights the association between multiple tree nut sensitivities, other allergic conditions, and elevated IgE levels. Further large-scale studies are needed to identify additional factors affecting the development of tree nut sensitivities in this age group, better understand these relationships, and develop more effective clinical approaches. Alongside parent education, regular monitoring of children’s nutrition and health is crucial. Given the possibility of cross-reactivity with multiple tree nut sensitivities, current guidelines recommend avoiding all tree nuts once a tree nut allergy diagnosis is made [14].
Our study, by identifying early detection of tree nut sensitivities, associated conditions, and relationships with inhalant and food allergens in children aged 0–5 years, aims to contribute to the application of environmental measures to prevent severe outcomes such as anaphylaxis and even death.
