Abstract
Background
To date, studies have mainly focused on the frequency and severity of the so-called big 8 foods; less is known about other foods.
Objective
We investigated the frequency and severity of allergy to all foods reported to cause food allergic symptoms.
Methods
Adult patients with symptoms within 2 hours after ingestion of any food were included. Sensitization was measured by skin prick test and/or specific IgE for the culprit food(s) when possible.
Results
A total of 1085 patients were included, of whom 66.9% had a probable food allergy (FA) (reported symptoms with sensitization) and 33.1% only a possible FA (reported symptoms, independent of sensitization). Patients reported symptoms to a total of 192 foods, and sufficient sensitization data were available for 45 foods. The ranking in frequency and severity of symptoms was comparable between probable and possible FA. Regarding possible FA, fruit was most commonly reported (68.8%), followed by nuts (63.0%), legumes (39.5%), vegetables (34.0%), and seeds or pits (14.4%). Severe symptoms were most frequently reported for seeds (39.8%), fish (39.2%), legumes (34.8%), nuts (31.9%), and crustaceans (31.3%), and least frequently for fruit (16.5%). Nevertheless, in absolute numbers, fruit ranked in position 3 (n = 125), with especially tropical fruit (eg, lychee) frequently causing severe symptoms. Regarding probable FA, severe symptoms were most common for sunflower seeds (80.0%), pine nut (66.7%), Brazil nut (60.0%), cashew (57.1%), and pistachio (51.7%).
Conclusion
Food allergies are caused by almost 200 different foods in adults. Although not mandatorily labeled, seeds most commonly cause severe symptoms, and fruit causes severe symptoms in a large number of patients. This study highlights the importance of food allergies outside the big 8.
Key words: Food allergy, severity, prevalence, coallergies, labeling, big eight, legumes, seeds, pits, fruit
Food allergy (FA) is an important global human health issue, and it imposes a growing societal burden.1 The estimated lifetime prevalence of FA in Europe has increased from 2.6% in 2000-12 to 3.5% in 2012-21,2 and it is expected to increase further in the future.1
Theoretically, any food can cause a FA, but prevalence studies have mainly focused on the so-called big 8 foods of cow’s milk, hen’s egg, wheat, soy, peanut, tree nuts, fish, and shellfish; less is known about the prevalence of FA for other foods.2, 3, 4, 5, 6 Two studies have shown that foods outside the big 8 that were traditionally not considered important are in fact highly relevant FAs, such as kiwi, peach, and apple.3,7 As a result of globalization, climate change, and a growing world population, there is change in dietary habits with a shift toward a more plant-based diet.4, 5, 6 As a result of this shift, it is expected that allergies to plant foods will increase. Furthermore, the introduction of novel foods can cause new FAs. Therefore, studies should not only focus on the big 8 but also on the prevalence and severity of food allergies for all foods, especially plant-based foods and novel foods.
Oral food challenge (OFC) remains the reference standard for diagnosing FA.8 However, in clinical practice, it is often not feasible to perform OFCs for all suspected foods in every patient. Sensitization tests support diagnosis, but for many foods, no commercial diagnostic tests are available. Diagnostic certainty can be improved through a detailed clinical history taken by an experienced allergology specialist. Additionally, one of our earlier studies demonstrated that the presence of oral allergy symptoms and allergic rhinitis are among the strongest predictors of probable FA.9 Studies often report data only for a limited number of foods for which both symptoms and sensitization are confirmed (probable FA). However, data on reported symptoms (possible FA) can be relevant as well. The lack of sensitization data for a number of foods reflects the diagnostic gap frequently encountered in clinical practice. In this study, we aimed to combine these categories to provide the best representation of all foods causing symptoms, based on clinical history taken by highly trained FA specialists, while incorporating sensitization data whenever available.
The aim of this study was to investigate the prevalence and severity of all foods that were reported to cause a reaction by adult patients at our outpatient allergology clinic.
Methods
Study population
All consecutive adult patients (≥ 18 years) who were referred to a tertiary-care center in the Netherlands, the allergology outpatient clinic of the University Medical Centre Utrecht, with reported symptoms to food within 2 hours after ingestion (possible FA) between July 2018 and September 2023 were included retrospectively. Patients were excluded if they reported symptoms after ingestion of a composite meal where the causative food ingredient was unclear, or if they objected to their data’s being used for research purposes.
This study was approved by the medical research ethics committee of the University Medical Centre Utrecht (protocol 22-983).
Data collection
Clinical questionnaire
Physicians systematically collected clinical information from all patients with a suspected FA during the first outpatient clinic visit using a standardized questionnaire. This involved demographics, allergic comorbidities, culprit food or foods, reported symptoms, severity, time interval, and prescription of emergency medication (antihistamines, prednisone, and/or epinephrine auto-injector).
Classification of severity
The validated oFASS-3 (Ordinal Food Allergy Severity Score 3) score was used to classify the severity; oFASS-3 grade 1 includes isolated oropharyngeal symptoms; grade 2 may include grade 1 symptoms, but at least symptoms of the skin, eye, upper airways, and/or digestive system, and grade 3 may include grade 1 and/or 2 symptoms, but at least symptoms of the lower airways and the cardiovascular and/or nervous system.10 Here we refer to a grade 1 reaction as mild, grade 2 as moderate, and grade 3 as severe.
Specific IgE measurements
Sensitization was measured by skin prick tests (ALK, Madrid, Spain), prick-to-prick tests, and serum-specific IgE (sIgE) tests (including component-resolved diagnostics) (ImmunoCAP; Thermo Fisher Scientific, Uppsala, Sweden) for foods for which tests were available. A mean wheal diameter of ≥3 mm and sIgE levels pf ≥0.35 kUA/L were considered positive, respectively. The tests performed in each patient were at the discretion of the physician and depended on factors such as the number of reported foods, the severity of the culprit food, availability of commercial tests for the food, and the patient’s wishes.
Definitions
Possible FA
Possible FA was defined as reported symptoms to food, independent of sensitization.
Probable FA
Probable FA was defined as reported symptoms and matching food sensitization.11 Probable FA was only investigated for foods for which sensitization was measured in at least 10 patients who also reported symptoms to these foods. Although using probable FA data is preferable over possible FA, diagnostic tests for many novel or less commonly consumed foods were unavailable and the diagnostic value of sIgE is not known for less common foods. Our aim was to assess the frequency and severity of all foods, and excluding patients with possible FA would implicate the loss of a significant portion of valuable real-word data. We investigated whether the severity differed between patients with a possible and probable FA for the foods for which diagnostic tests were available to see if severity could be generalized from possible FA to probable FA.
Food groups
To compare the frequency and severity of corresponding foods, the individual foods were classified into 14 food groups, as follows: (1) fruits, (2) nuts, (3) legumes, (4) vegetables, (5) seeds and pits, (6) dairy, (7) hen’s egg, (8) crustaceans, (9) fish, (10) grains, (11) mollusks, (12) spices and herbs, (13) meat, and (14) insects.
Coallergies
Coallergies were defined as reported symptoms to one food in patients who also reported symptoms to another food, regardless of their sensitization pattern.
Sensitization patterns in reactions to plant foods
Because plant foods are the most common allergenic sources in adults, and because this may become an even greater problem with a shift toward a more plant-based diet, the relationship between the severity of symptoms and the underlying molecular sensitization pattern of plant foods was investigated.
For this purpose, patients who reported symptoms to at least one plant food were divided into the following groups according to their sensitization pattern:
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PR-10 group: sensitization to only PR-10 protein and not to lipid transfer proteins (LTP) and seed storage proteins (SSP).
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LTP group: sensitization to only LTP and not to PR-10 and SSP.
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SSP group: sensitization to only SSP and not to PR-10 and SSP.
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PR-10/LTP group: sensitization to PR-10 and LTP and not to SSP.
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PR-10/SSP group: sensitization to PR-10 and SSP and not to LTP.
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LTP/SSP group: sensitization to LTP and SSP and not to PR-10.
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PR-10/LTP/SSP group: sensitization to PR-10, LTP, and SSP.
The following components were measured:
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PR-10: Cor a 1.0401 and/or PR-10 mix (Bet v 1, Que a 1, Mal d 1, Jug r 5, Ara h 8).
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LTP: LTP mix (Pru p 3, Tri a 14, Pha v 3, Lac s 1, Mal d 3, Jug r 3, Art v 3, Cor a 8, Ara h 9).
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SSP: Ara h 2, peanut storage mix (Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 7), Cor a 9, Cor a 14, nut storage protein mix (Ana o 3, Jug r 1, Ber e 1), Tri a 19.
IgE measurement for classifying the plant food groups was performed with customized immunoblots (EUROLine, EUROIMMUN, Lübeck, Germany). Sensitization was assessed according to the standard manufacturer’s instructions using the EUROBlotOne. The EUROLine intensity units (EL) were evaluated using the EUROLineScan software. Results of EAST class 1 or higher were considered positive.
Because immunoblots have been routinely measured in every patient since March 2022, the analyses of the subgroups that were based on sensitization patterns were performed on patients visiting our clinic from March 2022.
In addition to the abovementioned classification based on the immunoblot where multiple food mixes were measured, a classification based on ImmunoCAP was made for individual foods. For valid conclusions based on component-resolved diagnostics, all allergen families, or at least the most important allergen families, must be measured for the culprit food. Therefore, only those foods for which both PR-10 and non–PR-10 components were measured by ImmunoCAP were used.
Statistical analysis
Data were extracted from the hospital’s electronic health records. Continuous variables were described as means with standard deviation when normally distributed and as medians with interquartile range (Q1, Q3) when not normally distributed. Categorical variables were described as frequency and percentages. Patient characteristics were described for the total population.
The highest severity score per patient was defined and described. The frequency of reported symptoms and associated severity of the foods were ranked from most common to least common.
In patients with a plant FA, the severity of the different underlying molecular sensitization groups was compared by the chi-square trend test (linear-by-linear association) to account for the ordinal structure of the severity classification. P ≤ .05 was considered statistically significant.
Analyses were performed by SPSS Statistics v29.0 (IBM, Armonk, NY) and R v4.2.2 (www.r-project.org).
Results
Clinical characteristics
A total of 1085 adult patients reporting symptoms to 192 foods within 2 hours after ingestion (possible FA) were enrolled. Of these, 70.8% were female. Characteristics of these patients are listed in Table I. The most common atopic comorbidity was allergic rhinitis, which was present in 85.9% of patients. The median number of foods reported to cause a reaction within a patient was 5, with a maximum of 31. Of all the foods that were reported to cause a reaction per patient, the most severe reaction was mild in 17.6% of the patients, moderate in 40.8%, and severe in 41.6%.
Table I.
Patient characteristics with reported symptoms to foods within 2 hours after ingestion
| Characteristic | Possible FA | Probable FA |
|---|---|---|
| No. of patients | 1085 | 726 |
| Age (years), mean [standard deviation] | 37 [14] | 36 [14] |
| Female sex | 768 (70.8) | 494 (68.0) |
| History of atopic comorbidities∗ | ||
| Allergic rhinitis | 911 (85.9) | 660 (92.4) |
| Allergic asthma | 472 (44.9) | 355 (50.1) |
| Atopic eczema | 579 (55.0) | 433 (61.0) |
| Medication∗† | ||
| Antihistamine | 973 (93.1) | 681 (96.2) |
| Prednisone | 633 (66.5) | 463 (72.0) |
| Adrenaline auto-injector | 480 (55.8) | 347 (60.3) |
| No. of foods, median [IQR] | 5 [2-8] | 6 [3-9] |
| Highest severity score‡ | n = 1056 | n = 713 |
| Mild | 186 (17.6) | 116 (16.3) |
| Moderate | 431 (40.8) | 207 (37.9) |
| Severe | 439 (41.6) | 327 (45.9) |
| Fastest onset of symptom | n = 1085 | n = 726 |
| <5 minutes | 906 (83.5) | 649 (89.4) |
| 5-30 minutes | 138 (12.7) | 66 (9.1) |
| 30-120 minutes | 41 (3.8) | 11 (1.5) |
Data are presented as nos. (%) unless otherwise indicated. IQR, Interquartile range.
Percentage of available information.
Medication could be prescribed to treat FA and/or comorbidities.
Severity was defined as follows: mild, isolated oropharyngeal symptoms; moderate, symptoms of skin, eye, and/or upper airways with or without digestive system with or without mild symptoms; and severe, symptoms of lower airways, cardiovascular symptoms with or without nervous system with or without mild/moderate symptoms.
Because there is likely to be overreporting if only data on possible FA are taken into account, we also assessed probable FA (reported symptoms + sensitization). Enough sensitization data were available for 45 foods in 945 patients, of whom 726 were sensitized, resulting in 76.1% of patients with at least a probable FA (Table I). Data regarding age, sex, atopic comorbidities, medication, number of foods, highest severity score, and onset of symptoms were comparable between patients with possible and probable FA, supporting the value of data on possible FA.
Frequency and severity of allergic reactions in patients with a possible FA
Individual foods
Of the patients with a possible FA, apple allergy was most commonly reported, at 44.4% (see Table E1 in the Online Repository available at www.jaci-global.org). About a third of the patients reported symptoms to kiwi, hazelnut, walnut, or peanut; about a quarter to cherry; and a fifth to almond, peach, or pear. Almost 80% of the reported symptoms were caused by 30 foods and 20% by the remaining 162 foods, of which 35 foods were only reported once. Although mandatorily labeled, symptoms were uncommon for lupine (0.1%), fish (0.1-1.9%), crustaceans other than shrimp (0.2-1.4%), mustard (1.1%), and celery (2.5%).
When focusing on the frequency of severe symptoms of the individual foods for which at least 15 patients reported symptoms, pine nut, sunflower seed, peanut, cashew nut, and salmon most frequently caused severe symptoms (38.9-50.9%) (Table E1). However, in absolute numbers, peanut, hazelnut, walnut, almond, apple, and kiwi most commonly caused a severe reaction (51– 117 patients) because of the high number of patients reporting symptoms to these foods.
Food groups
The 192 foods were classified into 14 food groups (Fig 1). Plant-based foods most commonly caused symptoms: 68.6% of the patients reported symptoms to fruit, 63.0% to tree nuts, 39.5% to legumes, 34.0% to vegetables, and 14.4% to seeds and pits. These were followed by the animal foods dairy (13.7%), hen’s egg (7.7%), crustaceans (7.6%), and fish (6.8%). Fewer patients reported symptoms to grains (5.8%), mollusks (3.9%), spices and herbs (3.4%), meat (1.7%), and insects (0.1%).
Fig 1.
Frequency and severity of food groups reported to cause symptoms from least to most common. Patients could report symptoms for foods in more than one group, so total number of patients does not equal sum of patients with symptoms for each food groups. For severity score, only patients with known severity score were included.
Regarding severity, seeds and pits (39.8%) and fish (39.2%) most commonly caused severe reactions, followed by legumes, nuts, and crustaceans, to which about a third of patients reported severe reactions (Fig 1). When looking at absolute patient numbers, severe reactions were most frequently seen for nuts (n = 252), legumes (n = 218), and fruits (n = 149). This means that in absolute patient numbers, fruit belongs to one of the food groups most frequently causing severe reactions even though it is generally seen as a food causing mild symptoms.
Tree nuts and legumes
Food groups most frequently causing severe symptoms in absolute numbers were tree nuts and legumes. Therefore, these two groups are described in more detail.
The within-group differences in frequency were large for both groups, but the within-group differences in severity were small for tree nuts and large for legumes. Frequency and severity for each tree nut are shown in Table E2 in the Online Repository available at www.jaci-global.org. Symptoms to hazelnut were most common (58.3%), followed by walnut (47.5%), almond (32.2%), cashew nut (21.1%), and pecan nut (13.7%). Symptoms to Brazil nut, coconut, chestnut, beech nut, and kemiri nut were less common (<10%). On the basis of percentages, there was no large difference in severity, with almost all tree nuts causing severe symptoms in one third of patients.
Frequency and severity of legumes are shown in Table E2. Symptoms to peanuts were by far most common (73.9%), followed by soy dairy (16.8%) and other soy products (12.1%). Symptoms to bean, pea, lentil, chickpea, and lupine were less common (<10%). Peanut most often caused a severe reaction (41.1%), followed by soy dairy (34.4%), bean (27.9%), pea (25.0%), and lentil (22.2%). However, several foods did not cause any severe symptoms, particularly the more processed soy products like soy burger and tempeh, but also asparagus bean, tamarind, black bean, capuchins, and lupine. More than 1.5 times as many patients had severe symptoms to soy dairy than to other soy products.
In conclusion, both tree nuts and legumes most commonly caused severe symptoms, with almost all tree nuts causing severe symptoms in 30% of patients and legumes having a wider distribution of severity.
Other food groups
Detailed information about the frequency and severity of the other food groups is available in Tables E3-E14 in the Online Repository available at www.jaci-global.org. We discuss the most notable results here.
The fruits to which patients most frequently reported severe reactions were mostly tropical, with a severe reaction to lychee in 66.7%, papaya in 50.0%, jackfruit in 45.5%, both persimmon and pomegranate in 33.3%, fig in 31.8%, and mango in 20.3%. Except for mango and fig, these were fruits for which patients were less likely to report symptoms to (n < 15).
When patients reported symptoms to seeds and pits, it was mostly to sesame (n = 77) and pine nuts (n = 58), with severe symptoms in 37.9% and 50.9%, respectively. Symptoms to sunflower seeds and mustard were less common (n = 24 and n = 12, respectively) but just as severe, with 42.9% and 40.0% of the patients reporting symptoms, respectively.
Coallergies
Coallergies between food groups and within food groups are shown in Fig 2 and in Tables E15 to E20 in the Online Repository available at www.jaci-global.org. The most remarkable results are discussed here in more detail.
Fig 2.
Coallergy in patients with reported symptoms to seeds or pits.
The frequency of coallergies between the different seeds and pits was in general low (<45%) (Fig 2, Table E17). Adult patients with symptoms to sesame had low frequency of coallergies to other seeds and pits, with coallergy for pine nut being most common (20.8%). The highest rate of coallergies was seen for sunflower seed and poppy seed with sesame (41.7% and 45.5%, respectively), sunflower seed with pine nut (37.5%), and pumpkin seed with sunflower seed (38.9%). Of the patients with symptoms to seeds and pits, 79.5% also reported symptoms to tree nuts. Conversely, only 18.1% of patients with symptoms to tree nuts also reported symptoms to seeds and pits.
In the legume group, patients who reported symptoms to soy, beans, peas, lentils, and chickpea often had a coallergy for peanut (23.6-47.8%) (Table E16). Contrarily, patients who reported symptoms to peanut less often had a coallergy for the other legumes (0-5.7%). Coallergies between beans, peas, lentils, and chickpeas ranged between 11.1% and 55.0%.
Of the patients reporting symptoms to tree nuts, 29.5% to 52.8% of patients also reported symptoms to peanut, but among patients with symptoms to peanut, only 7.9% to 34% of the patients also reported symptoms to tree nuts, mainly to hazelnut, walnut, and almond (Table E18).
Within the fruit and vegetable group, there were relatively fewer coallergies than in the other food groups (Table E19 and E20). Related foods showed often coallergies. This was particularly noticeable for fruits like Rosaceae, berries, and citrus fruit. Other noteworthy coallergies were seen between the tropical fruit mango and jackfruit, persimmon and lychee, and fig and date.
Frequency and severity of allergic reactions in patients with probable FA
Enough sensitization data were available for 45 foods. However, the ranking of the frequency and severity of the different foods for patients with probable and possible FA were comparable (see Tables E21 and E22 in the Online Repository available at www.jaci-global.org). The most notable results are discussed below.
Frequency and severity of allergic reactions
Of the patients with a probable FA, apple allergy was most common (37.2%), followed by hazelnut (30.5%), peanut (24.8%), kiwi (22.0%), peach (15.9%), walnut (13.4%), and almond (12.7%). Almost 70% of the food allergic reactions were caused by these 7 foods and 30% by the remaining 38 foods. Although mandatorily labeled, a probable FA was uncommon for salmon (0.7%), codfish (0.6%), lobster (0.4%), krab (0.3%), and tuna (0.2%).
When focusing on the frequency of severe symptoms of the individual foods for which at least 5 patients were allergic, sunflower seeds, pine nut, Brazil nut, cashew nut, and pistachio most frequently caused severe symptoms (51.7-80.0%). However, in absolute numbers, peanut, hazelnut, apple, walnut, and almond most commonly caused a severe reaction (33-84 patients) because of the high numbers of patients reporting symptoms to these foods.
For 64.0% of the foods that were reported <15 times, patients reported more frequently moderate or severe symptoms than mild symptoms, while this percentage was 36.4% for foods that were reported at least 50 times. This indicates that patients are more likely to have a more severe reaction to foods that less frequently cause symptoms.
Association between sensitization pattern and severity in plant-based FA
Sensitization patterns were measured by immunoblot from March 2022. From this date, a total of 358 patients reported symptoms to foods, of whom 337 reported symptoms to plant-based food, and in 291 patients, sensitization was measured by immunoblot. Of the 291 patients in whom sensitization was measured, 78.7% patients were sensitized to PR-10, 26.8% to SSP, and 10.7% to LTP, and 15.5% were not sensitized to PR-10, SSP, and LTP. Monosensitization to PR-10 was the most common, occurring in half of the patients. For SSP and LTP, monosensitization occurred in 4.1% and 1.0% of patients, respectively. In total, 27.8% of the patients recognized a combination of the 3 allergen groups of which sensitization to PR-10/SSP was most common, at 65.4%.
The severity of reactions for the different sensitization groups is shown in Table E23 in the Online Repository available at www.jaci-global.org. There was no significant difference in severity between the groups (P = .278). Severe reactions were seen in 32.7% of the patients in the PR-10 group and in 50.0% of the patients in the SSP group. In the PR-10/SSP combination group, 35.8% had a severe reaction, which was higher than the PR-10–only group, but lower than the SSP-only group. The LTP group was too small for comparison.
For only 4 foods, component-resolved diagnostics were measured for multiple allergen families, namely hazelnut, peanut, apple, and kiwi. For hazelnut and apple, around 80% of the patients were monosensitized to PR-10, and for peanut and kiwi, this was 44.9% and 58.1%, respectively (see Table E24 in the Online Repository available at www.jaci-global.org). For hazelnut and peanut, patients monosensitized to non–PR-10 components had significantly more commonly severe symptoms compared to patients monosensitized to PR-10 components. However, this was not seen for apple and kiwi. For apple and kiwi, there was a numerical trend toward more severe symptoms for those monosensitized to the PR-10 components than those monosensitized to non–PR-10 components.
To conclude, around 80% of our study population recognized PR-10 protein, which is explained by the study’s location in a birch-endemic area. Sensitization to non–PR-10 proteins cause, especially in peanut and hazelnut, more often severe symptoms compared to sensitization to PR-10 proteins. However, PR-10 monosensitization can also cause severe symptoms.
Discussion
To our knowledge, this is the most comprehensive study to date investigating almost 200 foods that caused a possible FA and 45 foods that caused a probable FA in an outpatient allergology clinic. Although data on probable FA are preferred over possible FA, the ranking of foods in terms of frequency and severity was comparable in both groups. Therefore, to get the best estimate of all foods and food groups that contribute to the burden of FA, we also included foods causing possible FA. Almost 80% of the reported symptoms were caused by only 30 foods. Fruit, tree nuts, and legumes most commonly caused an allergy and insects, meat, and spices or herbs least commonly. Severe symptoms were most frequently reported for seed or pits, nuts, and legumes. Fruit was one of the most common causes of a severe reaction because of the high frequency of symptoms to these foods. The differences in severity were large for the different legumes, whereas in tree nuts there was no large difference in severity. Peanut-allergic patients often did not report symptoms to other legumes, whereas patients with symptoms to other legumes often experienced reaction to peanut.
Fruit and vegetables are relevant food allergies
The food groups that most commonly caused symptoms were all plant-based foods, with fruits, tree nuts, and legumes ranking highest. It is difficult to compare our data with other studies, because, as far as we know, there are no studies that have included so many foods. The EuroPrevall (Prevalence, Cost, and Basis of Food Allergy Across Europe) study investigated the frequency of 24 priority foods and other foods that caused symptoms between 2006 and 2009.12 We performed a post hoc analysis with the Dutch EuroPrevall outpatient clinic data for comparison (see Table E25 in the Online Repository available at www.jaci-global.org). Results were largely comparable: the 17 most commonly reported foods were similar (except for cow’s milk). Fruit, nuts, peanut, and vegetables topped the list. This confirms that foods outside the big 8, especially fruits and vegetables, are also important sources of food allergies.
The most noticeable difference was that more than twice as many patients in our study reported symptoms to tree nuts, pits, and tropical fruit compared to the EuroPrevall study. This might be explained by the change in consumption. Dutch consumption data showed a shift toward a more plant-based diet between 2007-10 and 2019-21: an increase of >20% of the consumption of legumes, fruit, vegetables, tree nuts, and seeds.13 In our study, around 85% had a probable plant FA, which was mainly associated with birch pollen–associated FA. The change in diet over years, and therefore the potential change in allergy, warrants regular monitoring of FA over the years.14
Foods that are mandatorily labeled do not always cause frequent or severe symptoms, and vice versa
Mandatory labeling is meant to protect allergic consumers.15 There are still undeclared allergens that potentially cause serious health risks.16,17 The frequency from high to low of our adult patients to the 14 labeled foods or food groups is listed in Table II.18
Table II.
Frequency from high to low of 14 labeled foods or food groups in adult study patients
| Rank | Food | Possible FA (%) | Probable FA (%) |
|---|---|---|---|
| 1 | Tree nuts | 52.6 | 41.5 |
| 2 | Peanut | 29.2 | 24.9 |
| 3 | Cow’s milk | 13.4 | 3.1 |
| 4 | Soy | 10.4 | 6.7 |
| 5 | Hen’s egg | 7.7 | 4.1 |
| 6 | Crustaceans | 7.6 | 4.2 |
| 7 | Sesame | 7.1 | 4.9 |
| 8 | Fish | 6.8 | 2.8 |
| 9 | Cereal | 5.3 | 1.2 |
| 10 | Celery | 2.5 | 1.0 |
| 11 | Mustard | 1.1 | NA |
| 12 | Mollusks | 0.7 | NA |
| 13 | Lupin | 0.1 | NA |
| 14 | Sulfur dioxide | —∗ | —∗ |
NA, Not applicable.
Additive; uncommon.
When comparing the 14 foods that require labeling with our results, it is noticeable that some foods causing frequent or severe reactions are not mentioned, and vice versa. For example, we have shown that pine nut and sunflower seed (both for patients with a probable and possible FA) most frequently cause severe symptoms and are not labeled, whereas symptoms were neither frequent nor (often) severe for lupine, fish, crustaceans other than shrimp, mustard, and celery. Because seeds and pits are not only consumed as a whole but rather are widely used in industrially produced compound foods, further attention needs to be paid to their relevance as a potential hidden allergen.
It is important to note that these numbers represent the patients in one European country, whereas food labeling applies across the whole European Union, and severity could be different elsewhere. For example, a celery allergy in Swiss subjects is severe in 31.6% of patients.19 This highlights the importance of prevalence and severity data for all food allergies for appropriate labeling in different countries.
Common fruits cause severe reactions in high absolute numbers and tropical fruits in high percentages
Fruit was one of the most common causes of a severe reaction as a result of the high frequency of symptoms to these foods. Although the literature states that fruit allergy is mostly mild, several studies have showed that it can also be severe.20, 21, 22 A study of 218 cases of food-induced anaphylaxis showed that fruits can cause anaphylaxis, with pitted fruit (not further specified), kiwi, and banana being the culprit foods.23 Another study investigating 250 cases of fruit-only–induced anaphylaxis showed that kiwi, banana, and mango were the leading causes of anaphylaxis.22 These reports are roughly in line with our findings, with kiwi, apple, cherry, peach, strawberry, and banana being the most frequently reported fruits, in absolute terms, that are linked to severe symptoms.
In relative terms, our adult patients reported most frequently severe symptoms to tropical fruits such as lychee, papaya, jackfruit, persimmon, pomegranate, fig, and mango. It is expected that consumption of exotic fruits will rise as a result of an increased availability by import,24 a growing interest in new flavors and fruit varieties,24 and travel. This may cause a rise in frequency and severity of food allergies to exotic fruits.
Large differences in frequency and severity of FA within the legume group
Because peanut allergy is one of the most frequent and severe food allergies, it is important to know whether consumption of other legumes puts peanut-allergic patients at high risk of a reaction. This is especially important because legumes are an important alternative protein source, and it is expected that consumption will rise in the future. We showed that only a minority of patients who reported symptoms to peanut also experienced a reaction to other legumes. However, patients with reactions to other legumes often also had symptoms to peanut. Within the legume group, there were large differences in frequency and severity of an allergy to the individual legumes.
Coallergies between seeds and pits variable
Seeds or pits was the food group that most commonly caused severe symptoms. We have shown that patients with symptoms to seeds or pits often also reported symptoms to tree nuts (in 80%), but not vice versa (18%). Studies of coallergies among tree nuts and seeds are limited. Brough et al25 showed that patients with a positive OFC to pine nut and sesame were more likely to have a positive OFC to tree nuts (8.3-83.3%) than vice versa (9.6-28.6%). This is in agreement with our findings. Therefore, patients reporting symptoms to seeds and pits have a higher chance of symptoms to tree nuts than the other way around.
Less is known about coallergies between seeds and pits. We showed that when patients reported symptoms to seeds or pits, they most often also reported symptoms to sesame. Other common coallergies were between pumpkin seed and sunflower seed (38.9%) and sunflower seed with pine nut (37.5%). More research is needed to determine the clinical reactivity between seeds and pits, especially because these have become increasingly popular as a result of their favorable nutritional profile.26
Strengths and limitations
The main limitation of this study was that we only had enough sensitization data for 45 foods, rather than for all 192 foods, and that OFC data were not included. Therefore, the results should be interpreted with caution. Nevertheless, the availability of sensitization data for 45 foods is quite substantial. Moreover, the majority of patients with possible FA also had probable FA, so they are experienced in recognizing and reporting food allergic symptoms. Unfortunately, for many foods, no commercial diagnostic tests are available, and prick-to-prick tests are not standardized. In addition, especially for less common foods, the diagnostic value of sIgE tests is unknown, and false-negative results are not uncommon.8,27,28 Because we are particularly interested in the prevalence of these less common foods and novel foods, we also investigated possible FA. A previous pan-European study investigated the predictive value of patient history and showed that reporting of oral allergy symptoms and allergic rhinitis comorbidity were strong predictors of probable FA. In our outpatient clinic, highly trained FA specialists took the patient history; because in our study population 85.7% reported allergic rhinitis and 75% reported oral allergy symptoms, and because we only selected patients who exhibited reaction within 2 hours, including 83.5% who exhibited reaction within 5 minutes after ingesting the food, FA likely occurs in the majority of our patients.9 Furthermore, we also investigated patients with probable FA and showed that the frequency of symptom severity with probable FA was comparable to patients with possible FA. Another limitation was that we excluded patients who reported symptoms after ingestion of a composite meal where the causative food ingredient was unclear, which could give rise to information bias. However, the potential bias was limited because most of the causative food ingredients were known for most patients. Last, the retrospective design of this daily practice study resulted in missing data—regarding sensitization, for example—but the inclusion of over a thousand patients ensured a rich and representative dataset.
To our knowledge, this is the first study that provides a comprehensive overview of all the foods that cause symptoms with corresponding severity in more than a thousand patients. We focused not only on the big 8 foods but on all foods that cause symptoms, including less commonly reported and novel foods.
Conclusions
FA can be caused by almost 200 different foods in adult patients. Seeds or pits, which are not mandatorily labeled, most frequently cause severe symptoms and are a common FA. Large differences in frequency and severity of FA were observed within the legume group. In absolute numbers, fruit is one of the most common foods causing severe reactions, with tropical fruit in particular causing severe symptoms in high percentage of patients. This study highlights the need for more knowledge about food allergies outside the big 8, preferably by a prospective study.
Key messages.
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Nearly 200 foods cause allergies.
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Seeds or pits and fruits often cause severe reactions, and legume allergies vary in frequency and severity.
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Studies investigating allergens outside the big 8 are important.
Disclosure statement
Disclosure of potential conflict of interest: R. van Ree reports consultancies for HAL Allergy BV, Citeq BV, Angany, Reacta Healthcare, Mission MightyMe, AB Enzymes, and The Protein Brewery; speaker fees for HAL Allergy, Thermo Fisher Scientific, and ALK; stock options from Angany. The rest of the authors declare that they have no relevant conflicts of interest.
Acknowledgments
We thank EUROIMMUN (Lübeck, Germany) for providing us with the customized immunoblots used for IgE measurement.
Supplementary data
References
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