Discussion

To our knowledge, this is the first study to investigate FIA attributed to plant-proteins recommended for individuals seeking to adopt PBDs (plant allergens; PAs) using data from a large cohort of FIA collected by the AVN over a 23-year period (2002–2024). Although prior publications have utilized the same dataset, this work focuses exclusively on PAs and provides a novel characterization of clinical phenotypes in adolescents and adults.21,32,33

Interestingly, our results showed that the total PA-related FIA cases remained stable in adults, whereas in adolescents they increased significantly after approximately 2017. The reasons for this increase are unclear. It may reflect changing dietary patterns in this age group driven by ethical and environmental concerns.34 Policy measures such as the French legislation mandating a weekly vegetarian meal in school canteens could be a contributing factor by increasing awareness of PBDs among adolescents.35 However a direct link between such policies and FA has not been established. Alternatively, the increase might partly reflect case-recording biases inherent to registry-based data, including changes in reporting practices over time.

In our study, eleven allergens accounted for 85% of all PA-related FIA cases. Wheat-induced FIA in this cohort followed a recognizable, well-described clinical phenotype. Wheat was the leading elicitor, particularly in early and middle-aged adults, and reactions were modulated by cofactors, consistent with wheat dependent exercise-induced anaphylaxis.15,36,37 While PE remained the predominant cofactor in adolescents, combination of cofactors, including alcohol and medication use were common in adults. Atopic comorbidities were uncommon but more frequent in adolescents, than in adults, aligning with prior age-related observations.36 Recurrent reactions, including urticaria or anaphylaxis, were common in both age groups and appears to be an important diagnostic consideration. Sensitization to ω-5 gliadin predominated across both age groups (CRD available for 60% of cases in both age groups), reinforcing its role as a key molecular marker of wheat-induced anaphylaxis. Additionally, isolated sensitization to lipid transfer protein (Tri a 14) was also observed in a few cases, particularly among adolescents consistent with previous reports describing Tri a 14 sensitization in younger patients.38

Within the legume family, peanut-induced anaphylaxis in our cohort followed a well-established age-dependent phenotype, occurring predominantly in adolescents and young adults with a pre-existing peanut-allergy.15,39 Soy is a major ingredient in plant-based foods due to its high protein content.40 Consistent with previous reports, soy-induced anaphylaxis in adults was associated with BPA, PR-10 sensitization (Gly m 4, Bet v 1), and ingestion of large quantities, most commonly soy beverages.15,41 Our data extends these findings by identifying a possible adolescent phenotype. This phenotype was characterized by reactions in the context of pre-existing legume-allergy and a relative predominance of sensitization to seed storage proteins (Gly m 5 and Gly m 6) which may suggest cross-reactivity. However, given the small adolescent sample size and the incomplete CRD data, this age-specific phenotype would need confirmation in future AVN data. Lupin also emerged as a frequent elicitor of FIA, particularly in adults.42, 43, 44, 45, 46 In our cohort, lupin-induced FIA showed a female predominance in adults. In adolescents it occurred predominantly in those with pre-exisitng legume allergy. This female predominance warrants confirmation in larger studies. Possible contributing factors include sex-hormone influences, greater PBD adoption among women leading to differential dietary exposure, and cutaneous sensitization via lupin-derived ingredients in dermocosmetic products, though these remain unproven.47, 48, 49 Other legumes used in PBDs, such as pea and lentil, were less frequently implicated in anaphylaxis among both adolescents and adults. This is consistent with the currently available evidence on pea and lentil allergy, which is mostly reported in pediatric age groups.50, 51, 52 Their lower frequency as triggers of FIA in older age groups suggests that peas and lentils may represent relatively lower-risk plant protein options from adolescence onwards. 50, 51, 52

Buckwheat, a gluten-free pseudocereal increasingly used in Europe as a sustainable alternative to traditional cereals, is an emerging allergen.32,53, 54, 55 Buckwheat-induced anaphylaxis was more frequently reported in middle-aged adults than in adolescents. Aside from a higher proportion of adolescents with pre-existing buckwheat-allergy, no other major differences were observed between the 2 age groups. Overall, no clear association with cofactors or BPA was identified, and reactions can occur at both small-large quantities, with no distinct clinical phenotype emerging.

Among tree nuts relevant to PBDs, hazelnut was a common FIA elicitor in both age groups with no clear age-specific clinical differences. Reactions were often cofactor-associated, and BPA was common, consistent with birch pollen-driven sensitization via PR-10.56 Whereas earlier studies reported cashew allergy predominantly in children,15,57 our data extend these findings by showing that in adolescents cashew-induced anaphylaxis mainly occurred in individuals with pre-existing cashew allergy, while in adults reactions were more often associated with cofactors. Walnut-induced anaphylaxis showed no distinct age-specific patterns apart from higher rates of pre-existing allergy in adolescents. Across both age groups, cofactors were frequently implicated. Consistent with previous reports, almond-induced anaphylaxis occurred predominantly in adults, typically following ingestion of larger amounts.57

Seeds have gained prominence due to their high nutritional value.58 Among them, sesame is the most frequent elicitor of FIA across both adolescents and middle-aged adults, with no clear clinical phenotype. Cofactors were involved in approximately one-third of cases, while pre-existing sesame-allergy was more common in adolescents. Pine nut is the second most frequent seed-related elicitor of FIA, affecting adolescents and young adults at similar rates. Cofactor involvement, mainly alcohol, was more often reported in adults.

Most reactions followed exposure to small amounts (<1 teaspoon–1 tablespoon), primarily involving peanut, tree nuts, sesame, pine nut. Reactions to unidentified allergen were reported in up to 22.3% of peanut, lupin (19%), pine nut (19.2%), buckwheat (16.7%) and sesame (14.6%) cases. Particular attention is warranted for pine nut and buckwheat in absence of mandatory allergen labeling in the European Union.59

Adoption of PBDs in food-allergic or atopic individuals may benefit from consideration of age-specific clinical patterns. In adults, BPA was common among FIA involving soy typically following larger exposures. Hazelnut and almond-related FIA in adults were also frequently associated with BPA and could be triggered by small to large exposures. Wheat was the most frequent elicitors in adults. Across these PA-related FIA, reactions commonly occurred in the presence of diverse cofactors, often combined, including alcohol, medications and PE. In adolescents, PE was typically the main cofactor in most of the PA-related FIA cases. Peanut, cashew, walnut, sesame and buckwheat anaphylaxis more often occurred in the context of pre-existing allergy to the culprit allergen. Soy and lupin anaphylaxis occurred commonly in individuals with a known legume-allergy. Similar to adults, hazelnut reactions were common in individuals with BPA. Clinical phenotype of wheat-related reactions were similar to adults.

For sesame, pine nut, and buckwheat heterogeneous clinical presentations limited the ability to draw age-specific phenotypes.

Thus, distinct clinical patterns emerged across certain PA triggers of FIA, allowing differentiation between allergens with age-specific clinical phenotypes and those with heterogeneous presentations. This distinction is clinically relevant, as it provides a framework for dietary counseling in food-allergic or atopic adolescents and adults considering adoption of PBDs (Fig. 5).