Tolerance of peanuts and tree nuts in Spanish children with exclusive sensitization to lipid transfer proteins.

BACKGROUND: Allergy to peanuts and tree nuts is a common cause of food allergy in Spain, with lipid transfer proteins (LTP) being the most frequently recognized panallergen. LTP sensitization often leads to multiple food group sensitivities, resulting in overly restrictive diets that hinder patient's quality of life. This study aimed to assess the tolerance of peanuts and tree nuts (hazelnuts and walnuts) in children sensitized to LTP, potentially mitigating the need for such diets. METHODS: This prospective study enrolled individuals diagnosed with allergy to peanuts, hazelnuts, or walnuts. Data were collected from medical records, including demographics and clinical history. Allergological assessment comprised skin prick tests using commercial extracts and the nuts in question, alongside measurements of total and specific IgE to nuts and their primary molecular components. Participants showing positive LTP sensitization without sensitization to seed storage proteins underwent open oral nut challenges. RESULTS: A total of 75 individuals labeled as allergic to peanuts, 44 to hazelnuts, and 51 to walnuts were included. All of them underwent an open oral provocation test with the incriminated nut, showing a high tolerance rate. Peanut was tolerated by 98.6% of patients, 97.72% tolerated hazelnut, and 84.3% tolerated walnut. CONCLUSION: The findings suggest that the majority of patients allergic to peanuts, hazelnuts, or walnuts, due to LTP sensitization and lacking IgE reactivity to seed storage proteins, can tolerate these nuts. This supports the need for personalized nut tolerance assessments to avoid unnecessary dietary restrictions.

Poppy Seed Allergy: Molecular Diagnosis and Cross-Reactivity With Tree Nuts.

BACKGROUND: Poppy seed (PS) can be a cause of severe allergic reactions, especially in individuals with concurrent allergy to tree nuts and other seeds, but diagnostic criteria and sensitization patterns are lacking. OBJECTIVE: To assess the role of PS extract and individual allergens in diagnosing PS allergy and their cross-reactivities with tree nuts and buckwheat. METHODS: Our retrospective study included 36 PS-sensitized patients; 10 with a positive and 26 with a negative oral food challenge (OFC). We identified individual PS allergens and compared the diagnostic performance of specific IgE (sIgE) to PS extract with its allergens. Cross-reactivities between PS and related allergens from other seeds were assessed by a competitive enzyme-linked immunosorbent assay. RESULTS: We identified 4 novel PS allergens: Pap s 1 (vicilin), Pap s 1 (27-424) (α-hairpinin), Pap s 2 (legumin), and Pap s 3 (small hydrophilic seed protein). A positive OFC correlated with higher PS-sIgE levels and elevated sIgE levels for the PS allergens, except for Pap s 3. PS and α-hairpinin-sIgE effectively differentiated allergic from tolerant patients, with area under the curve values of 0.95 and 0.94. PS-sIgE >10.00 kUA/L exhibited 90% sensitivity and 73% specificity, whereas α-hairpinin-sIgE >2.60 kUA/L showed 100% sensitivity and 77% specificity. PS vicilin and legumin highly cross-reacted with hazelnut and buckwheat homologs, whereas α-hairpinin-sIgE cross-reacted with the related almond allergen. CONCLUSIONS: This is the most extensive study on PS allergy to date. PS and α-hairpinin-sIgE are highly sensitive indicators of clinical reactivity to PS, whereas vicilin and legumin-sIgE contribute to concurrent sensitization to hazelnut and buckwheat.

Validation of the NUT CRACKER Diagnostic Algorithm and Prediction for Cashew and Pistachio Co-Allergy.

BACKGROUND: Because of the high cross-sensitization among tree nuts, the NUT CRACKER (Nut Co-reactivity-Acquiring Knowledge for Elimination Recommendations) study proposed a diagnostic algorithm to minimize the number of required oral food challenges (OFCs). OBJECTIVE: To validate the algorithm for cashew and pistachio allergy and determine markers for allergic severity. METHODS: Patients (n = 125) with a median age of 7.8 (interquartile range, 5.9-11.2) years with suspected tree nut allergy were evaluated prospectively with decision tree points on the basis of skin prick test (SPT), basophil activation test (BAT), and knowledge of the coincidence of allergies. Validation of allergic status was determined by OFC. Markers of clinical severity were evaluated using the combined original and prospective cohort (n = 187) in relationship to SPT, BAT, and Ana o 3-sIgE. RESULTS: Reactivity to cashew in SPT, BAT, and Ana o 3-sIgE and the incidence of abdominal pain on challenge were significantly higher in dual-allergic cashew/pistachio patients (n = 82) versus single cashew allergic patients (n = 18) (P = .001). All 3 diagnostic tests showed significant inverse correlation with log10 reaction doses for positive cashew OFC. The algorithm reduced overall the total number of OFCs by 72.0%, with a positive predictive value and negative predictive value of 93.0% and 99.0%, respectively. Cashew false-positives were observed primarily in hazelnut-allergic patients (P = .026). In this population, Ana o 3-specific IgE could diagnose cashew allergy with a sensitivity of more than 90% and a specificity of more than 95%. CONCLUSIONS: The NUT CRACKER diagnostic algorithm was validated and reduced the number of diagnostic OFCs required. Markers for severity phenotypes may guide oral immunotherapy protocols, improving the risk/benefit ratio for patients.

Diagnosis and Management of Pollen Food Allergy Syndrome to Nuts.

Oral allergy syndrome or pollen food allergy syndrome (PFAS) represents a common clinical conundrum when the reported trigger food is a tree nut (usually almond or hazelnut) or peanut. The PFAS may give rise to uncertainty about the potential severity of the future reactions, indications for prescribing epinephrine, and the extent of the necessary dietary avoidance. As a food allergy, secondary to cross-reactivity with airborne pollen, PFAS usually manifests toward the end of the first decade of life as contact urticaria of the oropharyngeal mucous membranes. Molecular allergology facilitates diagnosis and risk stratification by establishing the profile of sensitization. Exclusive sensitization to pathogenesis-related proteins family 10 (PR10) and profilins indicates that signs and symptoms are due to PFAS, whereas sensitization to seed storage proteins with or without sensitization to PR10 and profilins may indicate a more severe primary nut allergy phenotype. Management relies on avoidance of the specific nut trigger, advice on the likelihood of more severe local or systemic symptoms, and treatment of reactions according to the severity. Future studies are needed to better delineate the risk of systemic reactions in individuals with nut PFAS and to establish the role of food or pollen allergen immunotherapy for the prevention or moderation of this condition.

Prevalence of tree nut allergy in Europe: A systematic review and meta-analysis.

In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published the first systematic review that summarized the prevalence of food allergy (FA) and food sensitization in Europe for studies published 2000-2012. However, only summary estimates for tree nut allergy (TNA) were feasible in that work. In the current update of that systematic review, we summarized the prevalence of tree nut allergy/sensitization to individual tree nuts. Six databases were searched for relevant papers published 2012-2021 and 17 eligible studies were added to the 15 studies already identified between 2000 and 2012, giving a total of 32 studies. Of the investigated tree nuts, meta-analysis was possible for hazelnut, walnut, almond, and in few cases, for cashew, and Brazil nut. The lifetime self-reported prevalence was 0.8% (95% CI 0.5-1.1) for hazelnut and 0.4% (0.2-0.9) for walnut. The point self-reported prevalence was 4.0% (2.9-5.2) for hazelnut, 3.4% (2.0-4.9) for Brazil nut, 2.0% (1.1-2.9) for almond, and 1.8% (1.1-2.5) for walnut. Point prevalence of food challenge-confirmed TNA was 0.04% (0.0-0.1) for hazelnut and 0.02% (0.01-0.1) for walnut. Due to paucity of data, we could not identify any meaningful and consistent differences across age groups and European regions.

The Severity and Frequency of Systemic Reactions to Hazelnut Are Significantly Higher in Hazelnut Allergic Patients Monosensitized to Cor a 8 than in Patients Polysensitized to Cor a 1, Cor a 8, and Cor a 9.

INTRODUCTION: Hazelnuts are a leading trigger of food allergy. To date, several molecular components of hazelnut are available for component-resolved diagnosis. However, little is known about how simultaneous sensitization to multiple allergens affects the severity of the hazelnut-induced reaction. In a previous study, our group demonstrated a lower risk of systemic reactions to peach in patients sensitized to both Pru p 3 and Pru p 1 than in the patient monosensitized to peach LTP. We aimed to assess whether this was also true in hazelnut allergy in a cohort of adult patients. METHODS: Patients were selected based on a history of symptoms such as urticaria, vomiting, diarrhea, asthma, and anaphylaxis indicative of hazelnut IgE-mediated food allergy and graded according to a clinical severity scale. For all patients, specific IgE was determined for Cor a 1 and Cor a 8 and, for most patients, also Cor a 9. Patients were offered an oral food challenge in open format (OFC) with a cocoa-based roasted hazelnut spread on a voluntary basis in order to prescribe an appropriate diet. RESULTS: A total of two hundred and fourteen patients were recruited. Among these, 43 patients were monosensitized to Cor a 8. One hundred and seventy-one patients were sensitized to Cor a 1 (79.9%), and, among them, 48/171 (28.1%) were also Cor a 8 positive. Cor a 9 was evaluated in 124/214 patients, testing positive in 21/124 (16.9%). Patients monosensitized to Cor a 8 experienced systemic reactions more frequently than those sensitized to Cor a 1 ± Cor a 8 (p < 0.00001), with significantly more severe reactions (p < 0.0005) and testing more frequently positive at OFC (p < 0.0001). Regarding Cor a 9, the sensitized patients were significantly younger (p = 0.0013) and showed reactions of similar severity to patients who tested Cor a 9 negative, and these reactions were milder than in patients monosensitized only to Cor a 8. DISCUSSION/CONCLUSION: Sensitization to Cor a 1 seems to protect from the development of the severe systemic reactions induced by Cor a 8 sensitization, Cor a 9 does not influence the severity of symptoms in adult patients. The OFC with roasted hazelnut may help in dietary guidance.

TreEAT trial: Protocol for a randomized controlled trial investigating the efficacy and safety of early introduction of tree nuts for the prevention of tree nut allergy in infants with peanut allergy.

INTRODUCTION: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy; however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi-nut oral food challenge (OFC) compared with standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. METHODS AND ANALYSIS: TreEAT is a 2-armed, open-label, randomized, controlled trial (RCT). Infants (n = 212) aged 4-11 months with peanut allergy will be randomized 1:1 at peanut allergy diagnosis to either a hospital-based multi-tree nut (almond, cashew, hazelnut, and walnut) OFC using multi-nut butter or standard care (home introduction of individual tree nuts). All infants will be assessed at age 18 months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine the allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion, and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety, and allergy-related healthcare visits from randomization to 18 months of age. Analyses will be performed on an intention-to-treat basis. ETHICS AND DISSEMINATION: TreEAT was approved by the Royal Children's Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT04801823.

Real-World Safety Analysis of Preschool Tree Nut Oral Immunotherapy.

BACKGROUND: Our group previously described preschool peanut oral immunotherapy (OIT) in a real-world, multicenter setting, suggesting that this therapy is safe for most preschoolers. OBJECTIVE: To examine the safety and tolerability of tree nut (TN) OIT in preschoolers in the real world. METHODS: As part of a Canada-wide quality improvement project, TN-OIT (cashew/pistachio, walnut/pecan, hazelnut, almond, and macadamia nut) was performed in preschoolers who had (1) a skin prick test wheal diameter greater than or equal to 3 mm or a specific IgE level greater than or equal to 0.35 kU/L and a convincing objective IgE-mediated reaction or (2) no ingestion history and a specific IgE level greater than or equal to 5 kU/L. Dose escalations were performed every 2 to 4 weeks till a maintenance dose of 300 mg of TN protein was reached. Symptoms were recorded and classified using the modified World Allergy Organization Subcutaneous Immunotherapy Reaction Grading System (1, mildest; 5, fatal). RESULTS: Of the 92 patients who started TN-OIT from 2018 to 2021, 79 (85.9%) underwent single-food TN-OIT and 13 (14.1%) underwent multifood TN-OIT to 2 (10.8%) or 3 (3.3%) TNs. Eighty-nine (96.7%) patients reached maintenance, and 4 (4.3%) dropped out. Sixty-five (70.7%) patients experienced reactions during buildup: 35 (38.0%) grade 1 reactions, 30 (32.6%) grade 2 reactions, no grade 3 or 4 reactions, and 2 (2.17%) received epinephrine. CONCLUSIONS: Preschool TN-OIT in a real-world, multicenter setting appears safe and tolerable, with results comparable with our previously reported peanut OIT findings.

Structure and IgE Cross-Reactivity among Cashew, Pistachio, Walnut, and Peanut Vicilin-Buried Peptides.

Peanut and tree-nut allergies are frequently comorbid for reasons not completely understood. Vicilin-buried peptides (VBPs) are an emerging family of food allergens whose conserved structural fold could mediate peanut/tree-nut co-allergy. Peptide microarrays were used to identify immunoglobulin E (IgE) epitopes from the N-terminus of the vicilin allergens Ara h 1, Ana o 1, Jug r 2, and Pis v 3 using serum from three patient diagnosis groups: monoallergic to either peanuts or cashew/pistachio, or dual allergic. IgE binding peptides were highly prevalent in the VBP domains AH1.1, AO1.1, JR2.1, and PV3.1, but not in AO1.2, JR2.2, JR2.3, and PV3.2 nor the unstructured regions. The IgE profiles did not correlate with diagnosis group. The structure of the VBPs from cashew and pistachio was solved using solution-NMR. Comparisons of structural features suggest that the VBP scaffold from peanuts and tree-nuts can support cross-reactivity. This may help understand comorbidity and cross-reactivity despite a distant evolutionary origin.