Brough, H.A., J.-C. Caubet, A. Mazon, D. Haddad, M.M. Bergmann, J. Wassenberg, V. Panetta, R. Gourgey, S. Radulovic, M. Nieto, A.F. Santos, A. Nieto, G. Lack, P.A. Eigenmann, 2020. Defining challenge-proven coexistent nut and sesame seed allergy: A prospective multicenter European study. J Allergy Clin Immunol. 145:1231-9.
Background: Peanut, tree nut, and sesame allergies are responsible for most life-threatening food-induced allergic reactions. Rates of coexistent allergy between these foods have been from mostly retrospective studies that include only a limited number of tree nuts or were not based on oral food challenges. Objective: The Pronuts study is a multicenter European study (London, Geneva, and Valencia) assessing the challenge-proven rate of coexistent peanut, tree nut, and/or sesame seed allergy. Methods: Children aged 0 to 16 years with at least 1 confirmed nut or sesame seed allergy underwent sequential diagnostic food challenges to all other nuts and sesame seed. Results: Overall, the rate of coexistent peanut, tree nut, and sesame seed allergy was 60.7% (n 5 74/122; 95% CI, 51.4% to 69.4%). Peanut allergy was more common in London, cashew and pistachio nut allergies were more common in Geneva, and walnut and pecan allergies were more common in Valencia. Strong correlations were found between cashew-pistachio, walnut-pecan, and walnut-pecan-hazelnut-macadamia clusters. Age (>36 months) and center (Valencia > Geneva > London) were associated with an increased odds of multiple nut allergies. By pursuing the diagnostic protocol to demonstrate tolerance to other nuts, participants were able to introduce a median of 9 nuts. Conclusion: We found a higher rate of coexistent nut and sesame seed allergies than previously reported. Performing sequential food challenges was labor intensive and could result in severe allergic reactions; however, it reduced dietary restrictions. Age was a significant predictor of multiple nut allergies, and thus the secondary spread of nut allergies occurred in older children.
Moraly, T., D.P. de Chambure, S. Verdun, C. Preda, M. Seynave, A.C. Vilain, C. Chenivesse, C. Delebarre-Sauvage, 2019. Oral immunotherapy for hazelnut allergy: a single-center retrospective study on 100 patients. J Allergy Clin Immunol Pract. https://doi.org/10.1016/j.jaip.2019.10.045
BACKGROUND: Oral immunotherapy (OIT) protects patients with IgE-mediated food allergies from food-induced allergic reactions due to accidental exposure and may improve their quality of life. This approach has never been evaluated for hazelnut, a major cause of food allergy in Europe. OBJECTIVE: We sought to determine the proportion of hazelnut-desensitized patients after 6 months of OIT and to identify predictors of successful desensitization. METHOD: In a retrospective single-center study, we included patients under 18 years of age who underwent at least 6 months of hazelnut OIT for IgE-mediated allergy, defined by history of hypersensitivity reaction after hazelnut ingestion, positive hazelnut skin prick test (SPT) or specific IgE, and positive double-blind, placebo-controlled food challenge (DBPCFC). Patients able to tolerate 1635 mg of hazelnut protein (approximately 8 hazelnuts) were considered to be hazelnut desensitized. We determined the proportion of desensitized patients after 6 months of OIT, searched for associations between baseline variables and successful desensitization, and estimated the frequency and severity of OIT-related adverse reactions. RESULTS: One hundred patients were included (64% male, median age 5 years). History of severe reactions was noted in 7% of cases. At 6 months, the proportion of desensitized patients was 34% (95%CI: 25-44). The median eliciting dose (defined as the amount of hazelnut protein provoking a hypersensitivity reaction during the DBPCFC) increased from 106 mg [IQR: 51-249] at baseline to 523 mg [IQR: 190-1635] after 6 months of OIT (p<0.0001). With longer therapy, the proportion of desensitized patients increased. Using multivariate analysis, successful desensitization was associated with older age (OR: 1.5, 95%CI: 1.2-2.2), smaller hazelnut SPT wheal diameter (OR: 0.61, 95%CI: 0.4-0.8), lower hazelnut specific IgE level (OR: 0.86, 95%CI: 0.72-0.98), and absence of cashew allergy (OR: 0.42, 95%CI: 0.12-0.64). Adverse reactions occurred in 30% of patients; none were severe. CONCLUSION: In a cohort of 100 patients aged 3-9 years, our results show for the first time that hazelnut OIT is associated with hazelnut desensitization and may be safe in the majority of patients undergoing this therapy.
Elizur, A., M.Y. Appel, L. Nachshon, M.B. Levy, N. Epstein-Rigbi, B. Pontoppidan, J. Lidholm, M.R. Goldberg, 2019. Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study. Lancet Child Adolesc Health. 3(5):312-321.
Background: The safety and efficacy of oral immunotherapy for tree nut allergy has not been demonstrated to date, and its effectiveness is complicated by the high prevalence of co-allergies to several nuts. This study aimed to investigate the use of walnut oral immunotherapy in the desensitisation of walnut and additional tree nuts in patients who are co-allergic to several nuts. Methods: In a single-centre, prospective cohort study (the Nut Co-Reactivity ACquiring Knowledge for Elimination Recommendations study) at the Institute of Allergy, Immunology, and Paediatric Pulmonology at the Yitzhak Shamir Medical Centre, we recruited patients aged 4 years or older who were allergic to walnut, with or without co-allergy to pecan, hazelnut, and cashew. The diagnosis of each food allergy was based on a positive skin prick test or specific serum IgE (≥0·35 kUA/L) to the corresponding nut together with a positive oral food challenge, unless an immediate (within 2 h of exposure) reaction in the past year had been documented. Patients with uncontrolled asthma or a medical contraindication to receive adrenaline were excluded. Patients were assigned to walnut oral immunotherapy or the control group (observation and strict dietary exclusion) on the basis of the order of presentation to the clinic. Oral immunotherapy began with a 4-day dose-escalation phase to establish the single highest tolerated dose, which was consumed daily at home for 24 days; subsequent monthly dose escalations were repeated until 4000 mg walnut protein was achieved. Patients who were desensitised to walnut continued to consume 1200 mg walnut protein daily for 6 months as maintenance. The primary outcome was walnut desensitisation (passing an oral food challenge with 4000 mg of walnut protein) at the end of the study, analysed by intention to treat. In patients who were co-allergic to pecan, hazelnut, and cashew, the proportion who achieved cross-desensitisation to these nuts in addition to walnut desensitisation was examined. Findings: 73 patients with a walnut allergy were enrolled between May 15, 2016, and Jan 14, 2018. 49 (89%) of 55 patients in the oral immunotherapy group were desensitised to walnut compared with none of 18 patients in the control group (odds ratio 9·2, 95% CI 4·3-19·5; p<0·0001). Following walnut desensitisation, all patients who were co-allergic to pecan (n=46) were also desensitised to pecan. Additionally, 18 (60%) of 30 patients who were co-allergic to hazelnut or cashew, and 14 (93%) of 15 patients who were co-allergic to hazelnut alone, were either fully desensitised or responded to treatment. 47 (85%) of 55 patients had an adverse reaction (mostly grade 1 or 2) during up-dosing in the clinic; eight patients required intramuscular epinephrine in response to a dose at home. Of 45 patients who had follow-up data for the maintenance phase, all maintained walnut desensitisation and one patient required epinephrine during this period. Interpretation: Walnut oral immunotherapy can induce desensitisation to walnut as well as cross-desensitisation to pecan and hazelnut in patients who have tree nut co-allergies, with a reasonable safety profile. A low daily dose of the allergen maintains desensitization.
Valcour, A., J. Lidholm, M.P. Borres, R.G. Hamilton, 2019. Sensitization profiles to hazelnut allergens across the United States. Ann Allergy Asthma Immunol. 122(1):111-116.
Background: Measurement of IgE antibody to hazelnut components can aid in the prediction of allergic responses to the food. Objective: To investigate the association between patient demographics (age, location) and patterns of allergic sensitization to hazelnut components across the United States and to investigate the degree of correlation between hazelnut sensitization with sensitization to other tree nuts, peanuts, and their components. Methods: Serum samples from 10,503 individuals with hazelnut extract specific IgE (sIgE) levels of 0.35 kUA/L or higher were analyzed for IgE antibodies to Cor a 1, 8, 9, and 14 by ImmunoCAP. A subset of these patients were analyzed for IgE antibodies to peanut, walnut, and cashew nut IgE along with associated components. Results: Among hazelnut sensitized individuals, children (<3 years old) were predominantly sensitized to Cor a 9 and Cor a 14. Conversely, Cor a 1 sIgE sensitization was much higher in adults than children, especially in the Northeastern United States. Cor a 8 sensitization was relatively constant (near 10%) across all ages. Cosensitization of hazelnut with other tree nuts and peanuts was related to correlation of IgE concentrations of individual component families. Conclusion: We conclude that sensitization to individual hazelnut components is highly dependent on age and/or geographic location. Component correlations suggest that cosensitization to hazelnut and walnut may be caused by their pathogenesis-related protein 10 allergens, nonspecific lipid transfer proteins, or seed storage proteins, whereas hazelnut and peanut cosensitization is more often caused by cross-reactivity of pathogenesis-related protein 10 (Cor a 1 and Ara h 8) and nonspecific lipid transfer proteins (Cor a 8 and Ara h 9).
