Goldberg, M.R., M.Y. Appel, K. Tobi, M.B. Levy, N. Epstein-Rigbi, M. Holmqvist, J. Östling, L. Nachshon, J. Lidholm, A. Elizur, 2024. Validation of the NUT CRACKER diagnostic algorithm and prediction for cashew and pistachio co-allergy. J Allergy Clin Immunol Pract. 12(5):1273-1282.
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.
Cuadrado, C., C. Arribas, A. Sanchiz, M.M. Pedrosa, P. Gamboa, D. Betancor, C. Blanco, B. Cabanillas, R. Linacero, 2024. Effects of enzymatic hydrolysis combined with pressured heating on tree nut allergenicity. Food Chem. 451:139433. https://doi.org/10.1016/j.foodchem.2024.139433
Hazelnut, pistachio and cashew are tree nuts with health benefits but also with allergenic properties being prevalent food allergens in Europe. The allergic characteristics of these tree nuts after processing combining heat, pressure and enzymatic digestion were analyzed through in vitro (Western blot and ELISA) and in vivo test (Prick-Prick). In the analyzed population, the patients sensitized to Cor a 8 (nsLTP) were predominant over those sensitized against hazelnut seed storage proteins (Sprot, Cor a 9 and 14), which displayed higher IgE reactivity. The protease E5 effectively hydrolyzed proteins from hazelnut and pistachio, while E7 was efficient for cashew protein hydrolysis. When combined with pressured heating (autoclave and Controlled Instantaneous Depressurization (DIC)), these proteases notably reduced the allergenic reactivity. The combination of DIC treatment before enzymatic digestion resulted in the most effective methodology to drastically reduce or indeed eliminate the allergenic capacity of tree nuts.
Gutiérrez-Díaz, G., D. Betancor, J. Parrón-Ballesteros, R.G. Gordo, E.S. Castromil-Benito, E. Haroun, M. Vázquez de la Torre, J. Turnay, M. Villalba, J. Cuesta-Herranz, C. Pastor-Vargas, 2024. Identification of new allergens in macadamia nut and cross-reactivity with other tree nuts in a Spanish cohort. Nutrients. 16(7):947. https://doi.org/10.3390/nu16070947
The consumption of macadamia nuts has increased due to their cardioprotective and antioxidant properties. However, this rise is consistent with an increase in the cases of macadamia nut allergy, leading to severe reactions. Although two Macadamia integrifolia allergens (Mac i 1 and Mac i 2) have been identified in Australian and Japanese patients, the allergenic sensitization patterns in Western European populations, particularly in Spain, remain unclear. For this purpose, seven patients with macadamia nut allergy were recruited in Spain. Macadamia nut protein extracts were prepared and, together with hazelnut and walnut extracts, were used in Western blot and inhibition assays. IgE-reactive proteins were identified using MALDI-TOF/TOF mass spectrometry (MS). Immunoblotting assays revealed various IgE-binding proteins in macadamia nut extracts. Mass spectrometry identified three new allergens: an oleosin, a pectin acetylesterase, and an aspartyl protease. Cross-reactivity studies showed that hazelnut extract, but not walnut extract, inhibited macadamia nut oleosin-specific IgE binding. This suggests that oleosin could be used as marker for macadamia-hazelnut cross-reactivity. The results show an allergenic profile in the Spanish cohort different from that previously detected in Australian and Japanese populations. The distinct sensitization profiles observed highlight the potential influence of dietary habits and environmental factors exposure on allergenicity.
Pasioti, M., P. Xepapadaki, A.G. Mathioudakis, J. Lakoumentas, E. Efstathiou, N.G. Papadopoulos, 2024. Current options in the management of tree nut allergy: A systematic review and narrative synthesis. Pediatr Allergy Immunol. 35(5):e14132. doi: 10.1111/pai.14132.
Tree nut allergy is a lifelong and potentially life-threatening condition. The standard of care is strictly avoiding the culprit nut and treating accidental reactions symptomatically. To evaluate potential therapeutic options for desensitizing patients with IgE-mediated tree nut allergy, we systematically searched three bibliographic databases for studies published until January 2024. We looked for active treatments of IgE-mediated allergy to tree nuts (walnut, hazelnut, pistachio, cashew, almond, pecan, macadamia nut, and brazil nut). We focused on allergen-specific immunotherapy (AIT) using oral (OIT), sublingual (SLIT), epicutaneous (EPIT), or subcutaneous (SCIT) delivery, or other disease-modifying treatments. We found 19 studies that met our criteria: 3 studies investigated sublingual immunotherapy, 5 studied oral immunotherapy to a single tree nut, and 6 used multi-food oral immunotherapy with or without omalizumab. The remaining studies investigated the effectiveness of monoclonal antibodies or IgE-immunoadsorption in multi-food allergic patients, including patients with tree nut allergy. The heterogeneity of the studies prevented pooling and meta-analysis. Oral immunotherapy, single or multi-nut, with or without omalizumab, was the most studied approach and appears effective in conferring protection from accidental exposures. Omalizumab monotherapy is the only approved alternative management for reducing allergic reactions that may occur with accidental exposure.
Goh, S.H., G.C. Yap, H.Y. Cheng, W.C. Chiang, J.Y. Soh, K.W. Chong, A. Goh, E.H. Tham, A. Tyebally, S. Ganapathy, I. Ibrahim, B.W. Lee, 2024. Trends in Childhood Anaphylaxis in Singapore: 2015-2022. Clin Exp Allergy. 54(8):585-595. doi: 10.1111/cea.14528.
Background: There has been limited data regarding the incidence of anaphylaxis in Asia. We aim to describe patterns in patient characteristics, triggers and clinical presentation of childhood anaphylaxis in Singapore. Methods: This was a retrospective review of emergency electronic medical records of children with anaphylaxis. Patients with the allergy-related diagnoses of anaphylaxis, angioedema, allergy and urticaria based on ICD-9 codes were screened. Cases fulfilling the World Allergy Organization criteria for anaphylaxis were included. Results: A total of 1188 cases of anaphylaxis were identified with a median age of 6.3 years. Extrapolating data from the study sites, from 2015 to 2022, the incidence rate of childhood anaphylaxis emergency visits in Singapore doubled from 18.9 to 38.8 per 100,000 person-years, with an incidence rate ratio (IRR) of 2.06 (95% confidence interval [CI] 1.70-2.49). In 2022, the incidence rate of food anaphylaxis was 30.1 per 100,000 person-years, IRR 2.39 (95% CI 1.90-3.01) and drug anaphylaxis was 4.6 per 100,000 person-years, IRR 1.89 (95% CI 1.11-3.25). The incidence rate in children aged 0-4 years quadrupled during the study period. Common triggers were egg (10.4%), peanut (9.3%), tree nut (8.8%), milk (8%), shellfish (7.8%) and non-steroidal anti-inflammatory drug (4.4%). The majority (88.6%) of patients were treated with intramuscular adrenaline. Total number of allergy-related visits did not increase over time between 2015 and 2019. Rates of severe anaphylaxis, namely anaphylactic shock and admission to high-dependency and intensive care, did not increase over time, with a mean incidence of 1.6, IRR 0.85 (95% CI 0.40-1.83) and 0.7, IRR 1.77 (95% CI 0.54-5.76) per 100,000 person-years, respectively. Conclusion: While the number of emergency visits due to childhood anaphylaxis has increased, the number of cases of allergy-related visits, anaphylactic shock and anaphylaxis requiring high-dependency and intensive care did not rise.
De Agrela-Mendes, I., M. Pedrosa, C. Gómez-Traseira, E. Phillips-Anglés, M. Rodríguez-Álvarez, S. Quirce, 2024. Tolerance of peanuts and tree nuts in Spanish children with exclusive sensitization to lipid transfer proteins. Pediatr Allergy Immunol. 35(7):e14204. doi: 10.1111/pai.14204.
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.
Turner, P., N. Dowdall, 2024. Flying with nut and other food allergies: unravelling fact from fiction. Arch Dis Child. 2024-327848. https://doi.org/10.1136/archdischild-2024-327848
There is a common perception that peanut/tree nut particles can be transmitted through aircraft ventilation systems and pose a significant risk to passengers with food allergies. In fact, food- induced allergic reactions are around 10–100 times less common during flights than ’on the ground’, perhaps because of the multiple precautions food- allergic passengers take when flying. We review the evidence for strategies to help prevent accidental allergic reactions while travelling on commercial flights (review registered at PROSPERO, ref CRD42022384341). Research studies (including aircraft simulations) show no evidence to support airborne transmission of nut allergens as a likely phenomenon. Announcements requesting ’nut bans’ are not therefore supported, and may install a false sense of security. The most effective measure is for passengers to wipe down their seat area (including tray table and seat- back entertainment system). Food proteins are often ’sticky’ and adhere to these surfaces, from where they are easily transferred to a person’s hands and onto food that might be consumed. Airline companies can help to facilitate this through pre- boarding. Passengers at risk of anaphylaxis should be prescribed two adrenaline [epinephrine] autoinjector devices, to carry on their person at all times—including when flying. Airlines should consider including a separate supply of ’general use’ adrenaline autoinjectors in the onboard medical kit for use in an emergency. All airlines should have clear policies relating to food allergies which are easily available from their websites or on request. These policies should be applied consistently by both ground staff and cabin crew, in order to provide reassurance to food- allergic passengers and their caregivers.
Shwe Yee, N., H.K. Ng, J. Zeng, J. Bao, D.E. Campbell, P.J. Turner, N.A. Lee, 2024. Development of cashew and pistachio ladders through a food-processing approach. Foods. 13(21):3440. https://doi.org/10.3390/foods13213440
Following successful oral immunotherapy (OIT) for peanut allergy using boiled peanuts (BOPI trial), this study investigated the potential of wet-thermal-processing-induced allergen modifi cation, specifically soaking and boiling (1–4 h) to reduce the allergenicity of cashew and pistachio allergens. In addition, this study provides a foundation of understanding for developing safer forms of cashew/pistachio administration for application in OIT by gradual exposure to increasing doses of modified allergens with reduced potency as an “allergen ladder”. An SDS-PAGE analysis and an intrinsic-fluorescence spectroscopy revealed altered tertiary structures of the allergens, leading to their denaturation and even degradation. Notably, the reduction in both allergen-specific polyclonal IgG and human-specific IgE (sIgE) binding correlated with the treatment time, with the most significant decrease observed after 4 h of boiling. In contrast, shorter soaking treatments showed negligible effects on the IgE-binding capacity of these nuts, therefore indicating a further need for optimization. These findings indicate that extended boiling effectively reduced the amounts of the highly potent allergenic component Ana o 3 in cashew and Pis v 1 in pistachio, as confirmed by ELISA using polyclonal anti-Ana o 3 antibodies, and an immunoblot showed decreased IgE epitope binding in cashew and pistachio allergens, which further modified their allergenic profiles. This approach shows promise as a viable method for offering a safer therapeutic option for cashew/pistachio allergy.
Breiding, M., M. Soomann, M. Roth, J. Trück, F. Bellutti Enders, 2024. Safety of oral immunotherapy for cashew nut and peanut allergy in children – a retrospective single-centre study. Swiss Med Wkly. 154(11):3691. https://smw.ch/index.php/smw/article/view/3691
AIM OF THE STUDY: Oral immunotherapy (OIT) is increasingly used for the treatment of childhood food allergies, with limited data available on cashew nut OIT. This real-life study investigated the safety and feasibility of cashew nut OIT, comparing it with peanut OIT, with a focus on the up-dosing process. METHODS: We analyzed cashew nut (n = 24) and peanut (n = 38) OIT cases with treatment initiated between 2018 and 2022 at the University Children’s Hospital Basel. All patients who commenced therapy within this time frame were enrolled without prior selection. Two different starting protocols were used. Within the up-dosing protocol, the nut intake was incrementally increased by 20–30% every 2 weeks until reaching a maintenance dose of 1g of nut protein. After consuming the maintenance dose regularly for 18–24 months, a second oral food challenge was performed. Patients who passed this challenge were considered desensitized. The safety of the therapy was evaluated based on the severity of adverse reactions during the up-dosing phase. Symptom severity was evaluated using the validated ordinal food allergy severity scale (o-FASS-5). RESULTS: Over the study period, 33% of cashew nut-allergic and 63% of peanut-allergic patients experienced mild to moderate allergic reactions. Severe allergic reactions occurred in five peanut-allergic children with high baseline allergen-specific IgE levels. Six patients with peanut, and none with cashew nut OIT, discontinued the therapy due to adverse reactions. The mean duration to reach the maintenance phase was longer for children with asthma or another food allergy. Among children who already underwent the second oral food challenge, desensitization was achieved in 91% (11 out of 12) of cashew nut- and 73% (11 out of 15) of peanut-allergic patients. CONCLUSION: Cashew nut OIT had a low severity of adverse reactions and was generally well-tolerated. However, patient characteristics influenced side effect risk and treatment duration, emphasizing the need for individualized OIT strategies.
Arribas, C., A. Sanchiz, M.M. Pedrosa, S. Perez-Garcia, R. Linacero, C. Cuadrado, 2024. Impact of heat and pressure processing treatments on the digestibility of peanut, hazelnut, pistachio and cashew allergens. Foods. 13(22):3549. https://doi.org/10.3390/foods13223549
Abstract: Food processing can alter protein biochemical properties, impacting immunoreactivity and allergenicity. A key feature of food allergens is their resistance to enzymatic digestion, particularly by pepsin and trypsin. This study compares the digestomes of raw and heat- and/or pressure-treated peanuts, hazelnuts, pistachios and cashews using the INFOGEST harmonized digestion protocol and analyzing their IgE-binding capacity through in vitro methods. Protein patterns from controls and digestomes were resolved by SDS-PAGE and tested with sera from allergic patients, confirmed by competitive ELISA for hazelnuts and peanuts. The results indicate that processing methods differently affect the gastrointestinal (GI) digestion of these allergens. Simulated GI digestion caused a significant destruction of protein structures, reducing but not eliminating IgE reactivity for all four nuts. Boiling for 60 min did not change the SDS-PAGE profiles, but it did stimulate enzymatic activity, decreasing IgE binding capacity. In contrast, applying heat and pressure led to a nearly complete inhibition of allergenic potential during simulated digestion. These findings suggest that employing intense food processing techniques and investigating the gastrointestinal effects of highly allergenic nuts could be crucial steps toward developing new hypoallergenic formulations.
