Hazelnut allergy in children and adults: diagnosis and underlying mechanisms

Abstract

Hazelnut is a frequently consumed tree nut. This thesis shows that allergic symptoms to hazelnut are common but highly variable in severity, and they differ between children and adults. Hazelnut allergy in adults is generally limited to mild and local symptoms in the oral cavity, whereas in children, more severe symptoms such as angio-edema, urticaria and dyspnea are frequently observed. In adults, hazelnut allergy is associated with birch pollen allergy, whereas in children, it is often accompanied by atopic dermatitis. A correct diagnosis is important, to advise appropriate dietary restrictions and emergency medication. In adults, a history with only oral symptoms specifically attributed to hazelnut in combination with birch pollinosis is convincing to diagnose a hazelnut allergy. A history of allergic reactions with previous ingestion of hazelnut is often unknown in children, because many children have an elimination diet solely based on sensitization. Therefore, the diagnosis in children strongly relies on diagnostic tests. The skin prick test (SPT) with hazelnut extract is a better predictor of a hazelnut allergy in children than laboratory tests for specific IgE to hazelnut. Although the SPT with hazelnut extract can reduce the number of double-blind placebo-controlled food challenges (DBPCFCs), a DBPCFC remains necessary in the majority of children to diagnose a hazelnut allergy. IgE to hazelnut seed storage proteins Cor a 9 and Cor a 14 was shown to be highly specific for a severe hazelnut allergy in children and adults. Determination of IgE to these components may identify almost all children and half of the adults with a severe hazelnut allergy, which may lead to a significant reduction in the number of high-risk DBPCFCs. The amount of hazelnut needed to elicit objective symptoms was comparable between children and adults. Several patient characteristics such as age, SPT to hazelnut extract and IgE to Cor a 9 and Cor a 14 influenced the threshold distribution curve (TDC) to hazelnut. Labeling information based on eliciting doses may improve the product choice of individuals with a severe hazelnut allergy. Allergy to peanut is common in individuals with a hazelnut allergy. Almost half of the children and adults with a sensitization to hazelnut seed storage proteins were also sensitized to their homologous proteins in peanut. This was shown not to be the result of IgE cross-reactivity, whereas at T cell level, cross-reactivity between hazelnut and peanut major allergens was observed. This suggests that cross-reactivity at T cell level may lead to IgE antibodies to related allergens that are not cross-reactive. This may explain the frequently observed co-sensitization to multiple tree nuts and peanut and may provide a basis to develop an immunotherapeutic target. In conclusion, our data show differences in clinical aspects of a hazelnut allergy between children and adults. Measurement of IgE to Cor a 9 and Cor a 14 may improve the diagnosis of a severe hazelnut allergy, which may result in a reduction of the number of DBPCFCs and unnecessary elimination diets. Better understanding of the mechanism leading to a concomitant hazelnut and peanut allergy may provide a basis for the development of preventive or therapeutic strategies.