**Background:** Hazelnut allergy is the most prevalent nut allergy in Europe, with symptoms ranging from mild oral allergy syndrome (OAS) to life-threatening anaphylaxis. The clinical presentation depends on sensitization profile: cross-reactive PR-10 proteins (Cor a 1) from birch pollen typically cause mild oropharyngeal symptoms, while primary sensitization to stable seed storage proteins (SSPs: Cor a 9, Cor a 14) and lipid transfer proteins (Cor a 8) is associated with systemic reactions. Unlike cow's milk or egg allergy, tree nut allergies tend to persist throughout life, with only approximately 10% of children outgrowing them. This review synthesizes current knowledge on natural history, diagnosis, and treatment of hazelnut allergy.
**Methods:** A literature search was conducted using PubMed and the Cochrane Library for articles published between January 2012 and December 2022 using keywords 'hazelnut' and 'allergy'. Article titles and abstracts were screened for relevance, duplicates removed, and additional references added during full-text review.
**Key Results:** Challenge-confirmed IgE-mediated tree nut allergy has a prevalence of less than 2%, with hazelnut being the most frequent trigger of hypersensitivity reactions in Europe. In Central and Northern Europe, Cor a 1 IgE is detected in 60-90% of hazelnut-sensitized individuals, typically associated with mild OAS. In the Mediterranean area, LTP sensitization (Cor a 8) prevalence ranges from 36-83%. Children under three years are predominantly sensitized to SSPs. Co-sensitization to multiple nuts occurs in 12-96.7% of patients, though more than half are clinically allergic to only 1-2 nuts. Sequence homology between hazelnut Cor a 14 and walnut Jug r 1 is 55%, with clinical cross-reactivity demonstrated. In 161 hazelnut-allergic subjects, 68% were also sensitized to peanuts, with clinical hypersensitivity in 45%.
For diagnosis, SPT wheal diameter >8 mm was associated with PPV >95% in one study but only 38% PPV in another. Hazelnut sIgE <0.35 kU/l had NPV of 88-100%, while PPV at ≥0.35 kU/l ranged from 37-57%. Component-resolved diagnosis showed that Cor a 14 and Cor a 9 have high NPV (>90% combined) for primary hazelnut allergy but low PPV. The basophil activation test combined with CRD showed 100% sensitivity and >97% specificity for Cor a 14.
For treatment, Enrique et al. conducted a DBPC SLIT trial in 41 adults showing mean eliciting dose increased from 2.29 g to 11.56 g, confirmed at one-year follow-up (mean 14.57 g). Moraly et al. reported 34% desensitization after 6 months of OIT in 100 children (median age 5 years), with increased success over longer therapy. Sabouraud et al. found 51.4% reached >120 mg tolerated dose after one year in 70 patients, though 2.9% had severe reactions and 24% developed hazelnut aversion. Walnut OIT produced cross-desensitization to hazelnuts in 53% of co-allergic patients (Elizur et al.) and 88% desensitization to multiple tree nuts (Scurlock et al.). Omalizumab adjunct therapy showed threshold increase from 13.8 mg to 35,328 mg in one pediatric case.
**Clinical Implications:** Distinguishing primary from cross-reactive hazelnut allergy is essential for appropriate management. Patients with sIgE to SSPs (Cor a 9, Cor a 14) and LTP (Cor a 8) require strict avoidance and epinephrine carriage due to risk of systemic reactions, while those with isolated Cor a 1 sensitization may tolerate cooked hazelnuts. Component-resolved diagnosis can reduce unnecessary oral food challenges. Allergen immunotherapy, though not yet standardized, shows promise for increasing tolerance thresholds and reducing reaction risk from accidental exposure. The combination of AIT with monoclonal antibodies like omalizumab may improve safety and efficacy, but evidence remains limited and long-term tolerance data are lacking.