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Food allergy represents a significant public health concern, with its prevalence increasing in recent decades. Tree nuts are among major allergenic foods, and allergies to them are frequently linked to severe and potentially life-threatening reactions. Data on the prevalence and natural history of tree nut allergy are limited. Primary nut allergy typically presents with rapid-onset IgE-mediated symptoms. Diagnosis can be confirmed by demonstrating a positive skin prick test (SPT), specific IgE (sIgE), or through an oral food challenge. Component-resolved diagnostics (CRD) can identify those with a high risk of anaphylaxis. The main management strategy involves avoiding the culprit allergen and treating symptoms after accidental exposure. New therapeutic options, such as sublingual immunotherapy, oral food immunotherapy, with or without omalizumab, and other monoclonal antibodies, are being investigated to modify tree nut allergy. Tree nut allergy is a lifelong disease with a low likelihood of resolution. The aim of this paper is to present the current data on the prevalence, diagnosis, natural history, and management options for tree nut allergy.

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 analysed 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 1 g 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 desensitised. 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, desensitisation 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, emphasising the need for individualised OIT strategies.

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., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Systematic scoping review, focusing on randomized clinical trials of recent research addressing tree nut allergy., Recent Findings: This review addresses published, unpublished, and re-analyzed studies on tree nut allergy definition, epidemiology, etiology, diagnosis, prognosis, and therapy., Summary: The importance of tree nut allergy spans nations, economies, and cultures. While broad themes in epidemiology, etiology, diagnosis, prognosis, and therapy are emerging, the next major advance in tree nut allergy will require large, robust studies to deliver results important to patients and families., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Oral immunotherapy (OIT) is a treatment option for patients with milk, egg, and peanut allergy, but data on the efficacy and safety of cashew OIT are limited., Methods: A cohort of 50 cashew-allergic patients aged ≥4 years, who were consecutively enrolled into cashew OIT (target dose 4000 mg protein) between 4/2016 and 12/2019. Fifteen cashew-allergic patients who continued cashew elimination served as observational controls. Co-allergy to pistachio and walnut was determined. Full desensitization rate and associated immunological changes in both groups were compared. Patients fully desensitized to cashew were instructed to consume a dose of 1200 mg cashew protein for 6 months and were then challenged to a full dose. Patients with co-allergy to pistachio or walnut were challenged to the respective nut., Results: Forty-four of 50 OIT-treated patients (88%) compared to 0% in controls tolerated a dose of 4000 mg cashew protein at the end of the study (odds ratio 8.3, 95% CI 3.9-17.7, p < 0.001). An additional three patients were desensitized to 1200 mg cashew protein, and three patients stopped treatment. Three patients (6%) were treated with injectable epinephrine for home reactions. Desensitized patients had decreased SPT, sIgE, basophil reactivity, and increased sIgG4, following treatment. Following cashew desensitization, all pistachio (n = 35) and four of eight walnut co-allergic patients were cross-desensitized to the respective nut. All (n = 44) patients consuming a low cashew dose for ≥6 months following desensitization passed a full-dose cashew OFC., Conclusions: Cashew OIT desensitizes most cashew-allergic patients and cross-desensitizes to pistachio. Safety is similar to OIT for other foods., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose of Review: Tree nut (TN) and seed allergies are frequent, and their prevalence appears to be on the rise. Allergic reactions associated with these foods are more frequently severe, and these allergies tend to persist into adulthood, consequently affecting quality of life. In this review, we summarize recent advances in diagnostic modalities and management strategies for TN/seed-allergic patients., Recent Findings: Clinical manifestations of TN and seed allergy range from asymptomatic sensitization to severe anaphylactic reactions. The use of emerging diagnostic tools such as component resolved diagnostics (CRD) and the basophil activation test (BAT) can help better predict clinical reactivity, the latter being currently reserved for research settings. Strict avoidance of all TN is generally not required, as most patients can tolerate select TN despite co-sensitization. Oral immunotherapy (OIT) is a promising alternative treatment instead of complete avoidance of culprit allergens, as it can safely increase the allergy threshold., Summary: Our recent understanding of co-reactivity between various TN and seeds has shaped management opportunities, including select TN introduction and optimization of OIT, two strategies which may improve quality of life. There is a need for better minimally invasive diagnostic methods for TN and seed allergy, with CRD and BAT being promising tools., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

We present a case of walnut allergy in a 24-year-old man. The allergy work up revealed sensitization to walnut including a positive skin prick test and a high value of walnut-specific IgEs. The patient showed an anaphylactic reaction during the double blind placebo-controlled food challenge, to a cumulative dose of 3.723 g of walnut protein. The oral food challenge resulted in counseling regarding strict walnut avoidance and optimization of the emergency management. At follow-up the patient reported that having adhered to the recommended dietary measures resulted in no further allergic reactions., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

It has been common practice to tell patients with allergy to peanut or tree nuts to avoid all nuts. Evidence that unnecessary avoidance of peanuts and eggs is associated with increased risk for developing anaphylaxis to those foods has changed how allergists view previous recommendations to avoid foods that have not caused a reaction. In the absence of evidence, collaborative decision making between clinicians and families should be used to decide whether to avoid tree nuts and how to safely introduce tree nuts into the diet. This article discusses the options for introducing tree nuts to children with peanut allergy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cashew plant (Anacardium occidentale L.) is the most relevant species of the Anacardium genus. It presents high economic value since it is widely used in human nutrition and in several industrial applications. Cashew nut is a well-appreciated food (belongs to the tree nut group), being widely consumed as snacks and in processed foods by the majority of world's population. However, cashew nut is also classified as a potent allergenic food known to be responsible for triggering severe and systemic immune reactions (e.g. anaphylaxis) in sensitised/allergic individuals that often demand epinephrine treatment and hospitalisation. So far, three groups of allergenic proteins have been identified and characterised in cashew nut: Ana o 1 and Ana o 2 (cupin superfamily) and Ana o 3 (prolamin superfamily), which are all classified as major allergens. The prevalence of cashew nut allergy seems to be rising in industrialised countries with the increasing consumption of this nut. There is still no cure for cashew nut allergy, as well as for other food allergies; thus, the allergic patients are advised to eliminate it from their diets. Accordingly, when carefully choosing processed foods that are commercially available, the allergic consumers have to rely on proper food labelling. In this sense, the control of labelling compliance is much needed, which has prompted the development of proficient analytical methods for allergen analysis. In the recent years, significant research advances in cashew nut allergy have been accomplished, which are highlighted and discussed in this review.

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 kU A /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 desensitisation., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Hazelnut allergy (HA) is one of the more common food allergies (FAs) in Europe with a prevalence of 0.2%. The gold standard for diagnosing FA is oral food challenge (OFC) with the culprit food. Another purpose of OFC is to identify the "threshold level" of food as the dose that elicits symptoms. In this way it is possible to avoid a strict elimination diet and to determine the minimal quantity of the culprit food tolerated by the patient., Objective: The aim of our study was to assess the efficacy and tolerability of hazelnut low-dose OFC (H-LDOFC) in children with HA., Methods: From January 2015 to December 2016, we retrospectively analyzed the charts of patients referred to Allergy Unit of Meyer Children's Hospital, Florence, Italy for a history of HA. Prick by prick (PbP) and specific serum IgE (s-IgE) to hazelnut were performed. We proposed conducting an H-LDOFC to parents of children with HA. The H-LDOFC was considered completed when a cumulative dose of 2.5 g of hazelnut was reached. We divided the patients who underwent the H-LDOFC into an asymptomatic and a symptomatic group. For statistics we used SPSS for Windows version 16.0 and conducted a t test for comparing the averages, considering a p value of < 0.05 significant., Results: Forty-three out of 70 patients (61.4%) with HA underwent an H-LDOFC. The PbP to hazelnut (mean ± SD) was 7.2 ± 2.9 mm and the s-IgE to hazelnut 25.3 ± 32.5 kU/L. Twenty-eight out of the 43 patients (65.1%) who underwent H-LDOFC reached the cumulative dose of 2.5 g of hazelnut. During the H-LDOFC, 20/43 patients (46.5%) had no reactions and 23/43 patients had a total of 55 reactions: 34 (61.8%) oral allergy syndrome, 8 (14.5%) rash, 6 (10.9%) abdominal pain, 2 (3.6%) urticaria, 2 (3.6%) angioedema, and 3 (5.4%) dyspnea. Atopic dermatitis was found to present the only statistically significant difference (p = 0.002) in patients with symptoms compared to asymptomatic patients during H-LDOFC., Conclusions: To our knowledge, this was the first study to assess the efficacy and tolerability of H-LDOFC in a pediatric population. Our study suggests that in children with HA, H-LDOFC is well accepted and safe because adverse reactions are mild and the majority are represented by localized symptoms (oral allergy syndrome) and efficient, especially in terms of improvement of quality of life. For these reasons it could be more extensively used in the treatment of HA., (© 2018 S. Karger AG, Basel.)

Objectives: This study aimed to evaluate the relationship between food allergen sensitisation patterns and allergic manifestations in Omani patients and highlight the importance of specific immunoglobulin E (IgE) testing., Methods: This retrospective study included all patients referred due to allergic manifestations to the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, from November 2012 to November 2016. Specific IgE blood testing was performed to determine sensitisation to common foods known to cause allergic reactions., Results: A total of 164 patients were referred to SQUH over the study period, with 35.4% presenting with one allergic manifestation, 48.8% with 2-3 and 15.9% presenting with more than three manifestations. There was a family history of allergies in 70.7% of patients. Eosinophil counts and total and specific IgE levels were elevated in 18.9%, 54.9% and 73.2% of patients, respectively. Patients demonstrated sensitisation to cow milk (47.6%), wheat (41.5%), chicken eggs (34.8%), mixed tree nuts (34.1%), lentils (33.5%), peanuts (32.9%), soy (32.3%), shrimp (23.2%) and fish (15.2%). Overall, 19.5% were sensitised to a single allergen, 14% were sensitised to 2-3 and 39.6% were sensitised to more than three allergens. Almost one-third (29.3%) of patients suffered from food-induced anaphylaxis, of which 85.4% were prescribed self-injectable adrenaline., Conclusion: To the best of the authors' knowledge, this study is the first to describe food allergen sensitisation patterns among Omani patients with allergic manifestations. In conjunction with clinical symptoms, the correct interpretation of specific IgE levels is important to diagnose food allergies and make safe decisions about reintroducing foods., Competing Interests: CONFLICT OF INTEREST The authors declare no conflicts of interest.

Tree nut allergy is a potentially life-threatening disease that is increasing in prevalence, now affecting 1% of the general population in the United States. While other food allergies often resolve spontaneously, tree nut allergies are outgrown in less than 10% of cases. Due to the likelihood of cross-sensitization to multiple tree nut allergens, the current treatment guideline is strict avoidance of all nuts once one tree nut allergy has been diagnosed. For example, walnut and pecan are highly cross-reactive, along with cashew and pistachio, but the extent of clinical, IgE-mediated cross-reactivity among other tree nuts remains unclear, therefore making avoidance of all tree nuts a safe approach. There have been recent advances in immunotherapy for food allergies. For instance, there are investigational immunotherapies for milk, egg and peanut allergies, specifically oral immunotherapy, sublingual immunotherapy and epicutaneous immunotherapy. However, there are no large randomized controlled clinical trials for tree nut allergies. Even though there has been less research into tree nut allergy immunotherapies, the evidence of T-cell cross-reactivity among tree nuts exists in animal models and in T cells from allergic patients indicates that immunotherapeutic interventions may be possible. Here, we review the literature regarding epidemiology, allergen homology and cross-reactivity among tree nuts, and explore how current findings can be employed for effective therapy., (© 2018 John Wiley & Sons Ltd.)

The prevalence of food allergy has risen dramatically in the last two decades. Primary care providers encounter food-allergic children on a daily basis. Although the standard of care has traditionally been strict avoidance of the allergen and advisement to carry an epinephrine autoinjector in case of an accidental exposure resulting in a severe reaction, food allergy research has progressed in the past decade concerning various immunotherapies that may provide an alternate treatment strategy. Oral immunotherapy (OIT), performed under the supervision of an allergist, is the most widely studied of these therapies. In the past, OIT has been available in the realm of clinical trials, but it is now being offered by a small but increasing number of allergists in private practice throughout the United States. Pediatric primary care clinicians should be aware of both the risks and possible benefits of this treatment, because they are likely to encounter patients who may inquire about OIT in their practices. In this case report, use of OIT will be reviewed in the treatment of a food-allergic child., (Copyright © 2018 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Background: Concurrent sensitization to peanut (PN) and tree nuts (TN), the most dangerous food allergies, is common. Current oral immunotherapy (OIT) is not fully satisfactory., Objective: To determine whether the herbal formula B-FAHF-2 (BF2) ameliorates PN/TN OIT adverse reactions and enhances persistence of a tolerant state., Methods: Concurrently sensitized PN-, walnut- (WN) and cashew (CSH)-allergic mice received 1-day PN/WN/CSH rush OIT plus 3 weeks of maintenance dosing, with or without 3 weeks prior and 3 weeks BF2 co-treatment. Anaphylactic symptom scores, core body temperatures, plasma histamine levels, basophil numbers, antigen-specific IgE, cytokine levels, and IL-4, INF-γ and Foxp3 gene promoter DNA methylation status, and their correlation with final challenge symptom scores were determined., Results: BF2+OIT-treated mice experienced significantly fewer and less severe adverse reactions than OIT-only-treated mice (P<.01) during the 1-day rush OIT build-up dose phase. Both OIT-only and BF2+OIT mice showed significant desensitization (P<.01 and .001, respectively) at 1 week post-therapy challenge, being greater in BF2+OIT mice. All sham-treated and 91% of OIT-treated mice experienced anaphylaxis whereas only 21% of BF2+OIT-treated mice exhibited reactions during 5-6 weeks of dose escalation single PN and TN challenges. Greater and more persistent protection in BF2+OIT mice was associated with significantly lower plasma histamine and IgE levels, increased IFN-γ/IL-4 and IL-10/IL-4 ratios, DNA remethylation at the IL-4 promoter and demethylation at IFN-γ and Foxp3 promoters. Final challenge symptom scores were inversely correlated with IL-4 DNA methylation levels (P<.0002) and positively correlated with IFN-γ and Foxp3 gene promoter methylation levels (P<.0011) (P<.0165)., Conclusions and Clinical Relevance: Combined BF2/OIT therapy was safer and produced longer post-treatment protection and more tolerance-prone immunological and epigenetic modifications than OIT alone. BF2/OIT may provide an additional OIT option for patients with concurrent PN/TN and other food allergies., (© 2017 John Wiley & Sons Ltd.)

Peanut nut and tree nut allergy are characterised by IgE mediated reactions to nut proteins. Nut allergy is a global disease. Limited epidemiological data suggest varying prevalence in different geographical areas. Primary nut allergy affects over 2% of children and 0.5% of adults in the UK. Infants with severe eczema and/or egg allergy have a higher risk of peanut allergy. Primary nut allergy presents most commonly in the first five years of life, often after the first known ingestion with typical rapid onset IgE-mediated symptoms. The clinical diagnosis of primary nut allergy can be made by the combination of a typical clinical presentation and evidence of nut specifc IgE shown by a positive skin prick test (SPT) or specific IgE (sIgE) test. Pollen food syndrome is a distinct disorder, usually mild, with oral/pharyngeal symptoms, in the context of hay fever or pollen sensitisation, which can be triggered by nuts. It can usually be distinguish clinically from primary nut allergy. The magnitude of a SPT or sIgE relates to the probability of clinical allergy, but does not relate to clinical severity. SPT of ≥ 8 mm or sIgE ≥ 15 KU/L to peanut is highly predictive of clinical allergy. Cut off values are not available for tree nuts. Test results must be interpreted in the context of the clinical history. Diagnostic food challenges are usually not necessary but may be used to confirm or refute a conflicting history and test result. As nut allergy is likely to be a long-lived disease, nut avoidance advice is the cornerstone of management. Patients should be provided with a comprehensive management plan including avoidance advice, patient specific emergency medication and an emergency treatment plan and training in administration of emergency medication. Regular re-training is required., (© 2017 John Wiley & Sons Ltd.)

Allergy to tree nuts has grown widespread among patients, specifically in the pediatric population, in recent years. In this review, we evaluate and summarize the literature specific to development and treatment of tree nut allergy. The cause of tree nut allergy, such as most food allergies, is unknown; there are theories regarding maternal dietary factors as well as sensitization related to cross-reactivity to peanut allergens. The gold standard for the diagnosis of tree nut allergy is the double-blind, placebo-controlled, oral food challenge; however, simpler and more cost-effective diagnostic methods, such as the skin prick test and serum-specific IgE are often used as a supplement for diagnosis. Management of tree nut allergy consists of dietary avoidance and using epinephrine to manage serious allergic reactions. Alternative therapeutic methods, such as oral and sublingual immunotherapy and modification of allergenic proteins are being explored to develop safer, more effective and long-lasting management of tree nut allergy. We comment on the current studies involving risk factors for sensitization, diagnosis and management of tree nut allergy.

Allergy to peanut and tree nuts is a major worldwide health concern. The prevalence of these allergies may be increasing, but the reasons for these increases remain unclear. This group of foods accounts for a large proportion of severe and fatal food-allergic reactions. These allergies present most often during childhood but can occur at any age. Resolution is possible but uncommon, and frequent lifetime reactions caused by accidental ingestion are a serious problem. The major allergens of peanut and most tree nuts have been identified, allowing for insights into patient diagnoses, clinical outcomes, and potential future immunotherapies., (© 2015 S. Karger AG, Basel.)

Recent studies on cashew nut allergy suggest that the prevalence of cashew nut allergy is increasing. Cashew nut consumption by allergic patients can cause severe reactions, including anaphylaxis. This review summarizes current knowledge on cashew nut allergy to facilitate timely clinical recognition and to promote awareness of this emerging food allergy amongst clinicians. The goal of this study is to present a systematic review focused on the clinical aspects of allergy to cashew nut including the characteristics of cashew nut, the prevalence, allergenic components, cross-reactivity, diagnosis and management of cashew nut allergy. The literature search yielded 255 articles of which 40 met our selection criteria and were considered to be relevant for this review. The 40 articles included one prospective study, six retrospective studies and seven case reports. The remaining 26 papers were not directly related to cashew nut allergy. The literature suggests that the prevalence of cashew nut allergy is increasing, although the level of evidence for this is low. A minimal amount of cashew nut allergen may cause a severe allergic reaction, suggesting high potency comparable with other tree nuts and peanuts. Cashew allergy is clearly an underestimated important healthcare problem, especially in children., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: IgE-mediated allergic reactions to cashews and other nuts can trigger life-threatening anaphylaxis. Proactive therapies to decrease reaction severity do not exist., Objectives: We aimed to determine the efficacy of pepsin-digested cashew proteins used as immunotherapy in a murine model of cashew allergy., Methods: Mice were sensitized to cashew and then underwent challenges with digested or native cashew allergens to assess the allergenicity of the protein preparations. Using native or pepsinized cashew proteins, mice underwent oral or intraperitoneal sensitization protocols to determine the immunogenic properties of the protein preparations. Finally, cashew-sensitized mice underwent an immunotherapy protocol with native or pepsinized cashew proteins and subsequent provocation challenges., Results: Pepsinized cashew proteins elicited weaker allergic reactions than native cashew proteins but importantly retained the ability to stimulate cellular proliferation and cytokine production. Mice sensitized with pepsinized proteins reacted on challenge with native allergens, demonstrating that pepsinized allergens retain immunogenicity in vivo. Immunotherapy with pepsinized cashew allergens significantly decreased allergic symptoms and body temperature decrease relative to placebo after challenge with native and pepsinized proteins. Immunologic changes were comparable after immunotherapy with native or pepsinized allergens: T(H)2-type cytokine secretion from splenocytes was decreased, whereas specific IgG(1) and IgG(2a) levels were increased., Conclusions: Pepsinized cashew proteins are effective in treating cashew allergy in mice and appear to work through the same mechanisms as native protein immunotherapy., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

The hygiene hypothesis, which was put forward more than 20 years ago by Strachan, proposes that the recent increase in allergic and autoimmune diseases is due to increasing hygiene standards. Since then, numerous epidemiologic and animal studies have provided support for this hypothesis and showed that certain microorganisms, helminths in particular, have immunomodulatory effects. More recently, studies have led to the identification of some of the mechanisms underlying these immunomodulatory effects. Substances, or crude extracts, produced by worms and responsible for these effects have been analyzed. Clinical trials have been performed mainly with pig whipworm, which was chosen because it is likely to be nonpathogenic in human subjects. Eggs of the pig whipworm (Trichuris suis ova) have been shown to be safe in multiple studies. Efficacy has been demonstrated in patients with inflammatory bowel diseases and in 1 case of pecan allergy. Altogether, this information supports further investigation of T suis ova in patients with immune-mediated diseases, particularly in areas in which there is currently no therapy, such as food allergy., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

There is no approved therapy for food allergy. The current standard of care is elimination of the triggering food from the diet and accessibility to epinephrine. Immunotherapy is a promising treatment approach. While desensitization to most foods seems feasible, it remains unclear if a permanent state of tolerance is achievable. The research team at Duke is pioneering immunotherapy for food allergies. Work here has evolved over time from small open-label pilot studies to larger randomized designs. Our data show that immunological changes associated with immunotherapy include reduction in mast cell reactivity, decreased basophil responses, decreased specific-immunoglobulin (Ig)E, increased IgG4 and induction of regulatory T cells. Immunotherapy has generated much excitement in the food allergy community; however, further studies are needed before it is ready for clinical use., (© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.)

Food allergies have increased significantly over recent decades and are the most common cause of admissions for anaphylaxis in childhood, particularly in children under 5 years of age. Current management of food allergy is limited to strict food allergen avoidance together with education on the recognition and emergency management of allergic reactions, and in some cases provision of self-injectable adrenaline. Although this supportive management approach is generally effective, it is burdensome for patients and families, and in turn leads to reduced quality of life. Patients with food allergy would benefit greatly from a definitive treatment that could achieve long-term tolerance. Recent studies demonstrate that oral immunotherapy (OIT) can induce desensitization and modulate allergen-specific immune responses. However, it remains uncertain whether long-term tolerance can be achieved with current OIT regimens. Increased allergen dose, duration of OIT and/or inclusion of an immune modifying adjuvant may enhance the tolerogenic potential of OLT. Allergic reactions during OIT are common, although severe reactions are infrequent. Oral immunotherapy holds promise as a novel approach to the definitive treatment of food allergy.

Background: Tree nut allergy is one of the common potentially life-threatening food allergies in children and adults. Recombinant food allergens offer new perspectives to solve problems of clinical and molecular allergology in diagnosis, research, and therapy of food allergies. So far, superoxide dismutase (s) has been identified as a panallergen and studied in different allergenic sources. Manganese Superoxide Dismutase (MnSOD) has also been reported in pistachio that may cause allergic reactions in atopic subjects. The aim of this study was to describe the cloning, expression, and purification of MnSOD from pistachio nut., Methods: The pistachio MnSOD was cloned and expressed in E. coli BL21 (DE3) using a vector pET-32b (+). A recombinant protein was purified by metal precipitation. The protein immunoreactivity was evaluated using patients' IgE binding by means of ELISA and immunoblotting assays., Results: The MnSOD gene from pistachio was successfully cloned and expressed in E. coli. The purified pistachio MnSOD was recognized by IgE in 10 (40%) out of the 25 sera tested. Our results also showed that this protein might trigger some cross-reactions toward IgE antibodies and thus could be considered as a panallergen., Conclusions: For the first time recombinant manganese superoxide dismutase from nut source was expressed as a possible allergen. This pistachio allergen could be a possible basis for cross-reactivity with MnSOD from other sources.

Nut allergy is known to impact on the quality of life (QoL) and anxiety of both the allergic child and their parents, but little is known about how the management of food allergy is associated with these variables. To investigate the impact of nut allergy on QoL and anxiety in mothers and children with nut allergy in order to identify management strategies that may influence these factors. Forty-one nut allergic children (age 6-16 yrs) and their mothers completed questionnaires to assess maternal and children's QoL (PedsQL, WHOQOL-BREF, FAQL-PB), anxiety (SCAS, STAI) and perceived stress scale (PSS). Children also completed a nut allergy specific QoL questionnaire. Demographic data, details of previous reactions, test results and management plans were collected using parent-report questionnaires and hospital notes. Children with nut allergy had poorer emotional (p = 0.004), social (p = 0.043), and psychological (p = 0.006) QoL compared to healthy normative data. Maternal and child QoL and anxiety were not influenced by the severity of previous reactions. Mother and child reported lower anxiety (p = 0.043 and p < 0.001 respectively) when the child was prescribed an epinephrine auto-injector. Anxiety was not associated with whether the child carried the auto-injector or whether they strictly avoided traces of nuts in foods. Prescribing auto-injectors is associated with reduced anxiety for food allergic children and their mothers, but is not associated with improved adherence with medical management or reduced risk-taking behavior.

We report on 2 patients with anaphylaxis rom Macadamia nut. Temporal relationship between consumption of the nut strongly suggested the diagnosis. Clinical suspicion was supported by the presence of positive specific IgE and/or the positive skin test and/or and the basophil activation test.

Aim: To describe parent-reported prevalence and management of peanut and nut allergy in school entrant children., Method: A population-based, cross-sectional study in the Australian National Capital., Results: Out of 3851 children, parents reported 127 had a strong allergic reaction to peanuts and 19 to other nuts ever. Nut allergy ever prevalence was 3.8% (95% confidence interval 3.2-4.4%), and of peanut allergy ever 3.3% (2.8-3.9%). Children with nut allergy were more likely to have a general practitioner (odds ratio 2.64, 1.16-6.03), hay fever (3.78, 2.67-5.36), eczema (4.54, 3.15-6.56) and wheeze in the last 12 months (3.19, 2.22-4.59) and have been breastfed (2.68, 1.26-5.77) than those who did not. At follow up of 109 children with parent-reported allergy (75% response), 70% had diagnostic test-confirmed sensitisation, 32% had been prescribed an adrenalin autoinjector (6% had used one) and 46% were not eating peanut. Increasing severity of reported symptoms following consumption of peanut was associated with an increasing likelihood of recommended management. Based on parent report, the projected estimated diagnostic test-confirmed prevalence of peanut sensitisation was 2.4% (1.9%, 3.0%) for the entire sample., Conclusion: Among a highly representative sample of children at school entry, 1 in 30 parents reported their child to have a strong allergic reaction to nuts and over 1 in 50 are estimated to have diagnostic test-confirmed peanut sensitisation, based on parent report.

Purpose of Review: Hazelnut allergy can vary between mild oral symptoms and potentially dangerous anaphylaxis. There is a need to predict which subjects are at risk for severe reactions. In this study, possibilities for 'component-resolved diagnosis', based on sensitization to different allergens in hazelnut, are discussed., Recent Findings: One type of hazelnut allergy can be associated with sensitization to homologues of pollen allergens, predominantly birch, in hazelnut: Cor a 1 (Bet v 1) and Cor a 2 (profilin). These allergens account for relatively mild symptoms. However, subjects can also be sensitized to several other allergens in hazelnut that are related to more severe symptoms. These allergens are homologues of allergens in other nuts and peanut: Cor a 8 (lipid transfer protein) and Cor a 9 (11S globulin) and perhaps Cor a 11 (7S globulin). The clinical relevance of these and other potential hazelnut allergens has to be further defined. The diagnosis of hazelnut has to be confirmed by oral double-blind placebo-controlled food challenge., Summary: Sensitization to hazelnut can either be associated with mild oral symptoms, depending on sensitization to pollen, or with more serious allergic symptoms, related to sensitization to homologues of nut and peanut allergens.

Peanut and tree nut allergies were once thought to be permanent. Recent studies have shown that about 20% and 10%, respectively, of young patients may outgrow peanut and tree nut allergies. For the majority of patients, however, the natural history is not favorable. In addition, approximately 8% of patients who outgrow peanut allergy may suffer a recurrence. The rising prevalence of these allergies, coupled with the knowledge that allergic reactions to these foods have the potential to be severe or fatal and that accidental exposures are common, makes developing effective treatments to alter the natural history of peanut and tree nut allergies even more crucial for those who will not outgrow them. At this time, avoidance of the offending foods and being prepared to treat a potential reaction after accidental ingestion is the only treatment, but many promising therapeutic interventions are being investigated.

Anaphylaxis due to the ingestion of peanuts is a serious, common condition, known to both the general public and physicians. Recently, an increasing number ofpatients with an anaphylactic reaction after eating small amounts of cashew nuts have been reported. In three children, a boy aged 7 and two girls aged 9 and 10 years, respectively, with heterogeneous case histories involving allergic upper airway and conjunctival symptoms and constitutional eczema, allergy for cashew nuts was diagnosed in the first two and allergy for peanuts in the third. They were given dietary advice and an adrenaline auto-injector for emergencies. In most cases, a detailed food history, together with the demonstration of IgE against cashew nuts by means of serology or skin prick tests, are sufficient to establish the diagnosis. If the clinical relevance of a sensitisation to cashew nuts is unknown, a food provocation test may be necessary. The treatment consists of dietary intervention, and an adrenaline auto-injector is prescribed for a serious anaphylactic reaction. So far, three major allergens from the cashew nut (Anacardium occidentale) have been identified and purified.

Food allergies are more and more numerous, and frequent in children at all ages. At any moment, a clinical manifestation, quickly evolutive and alarming, must need the help call at phone 15, and the intervention of a medical team of SMUR. The departmental, free, cell to 15 for all medical emergencies note a regular increase of these specific calls since ten years, as this following case report shows it.

Purpose of Review: Food allergy may be life threatening and its management continues to consist of avoiding relevant allergens and, in the case of accidental ingestion, initiation of appropriate emergency therapy. The aim of this article is to describe current treatment approaches and discuss attempts to use specific immunotherapy for food-allergy treatment., Recent Findings: A recent study reports the use of sublingual immunotherapy for hazelnut food allergy in hazelnut-allergic patients. A significant increase in tolerance to hazelnuts after sublingual immunotherapy as assessed by double-blind, placebo-controlled food challenge, and good tolerance to this treatment, have been observed., Summary: The purpose of this review is to highlight the most promising novel approaches for treating food allergy beyond allergen avoidance. Some of these approaches alone, such as traditional Chinese herbal medicine, anti-immunoglobulin E therapy or sublingual immunotherapy for food allergy, or the combination of different approaches, would probably offer the best treatment option for food-allergic patients in the near future.

Nuts are a well-defined cause of food allergy, which affect approximately 1 % of the general population in the UK and the USA. There do appear to be differences in the frequency of nut allergy between different countries because of different dietary habits and cooking procedures. For example, in the USA and France, peanuts are one of the most frequent causes of food allergy, but in other countries, it seems to be less common. Genetic factors, in particular, appear to play a role in the development of peanut allergy. While the majority of nut allergens are seed storage proteins, other nut allergens are profilins and pathogenesis-related protein homologues, considered as panallergens because of their widespread distribution in plants. The presence of specific IgE antibodies to several nuts is a common clinical finding, but the clinical relevance of this cross-reactivity is usually limited. Allergic reactions to nuts appear to be particularly severe, sometimes even life-threatening, and fatal reactions following their ingestion have been documented. Food allergy is diagnosed by identifying an underlying immunological mechanism (i.e. allergic testing), and establishing a causal relationship between food ingestion and symptoms (i.e. oral challenges). In natural history investigations carried out in peanut-allergic children, approximately 20 % of the cases outgrew their allergy or developed oral tolerance. The treatment of nut allergies should include patient and family education about avoiding all presentations of the food and the potential for a severe reaction caused by accidental ingestion. Patients and families should be instructed how to recognise early symptoms of an allergic reaction and how to treat severe anaphylaxis promptly.

Background: Food allergy may be life-threatening, and patients affected need to receive accurate diagnoses and treatment. Hazelnut has often been implicated as responsible for allergic reactions, and trace quantities can induce systemic reactions., Objective: The aim of this study was to evaluate the efficacy and tolerance of sublingual immunotherapy with a standardized hazelnut extract in patients allergic to hazelnut., Methods: This was a randomized, double-blind, placebo-controlled study. Inclusion criteria were a history of hazelnut allergy and positive skin prick test and double-blind placebo-controlled food challenge results. Patients were then randomly assigned into 2 treatment groups (hazelnut immunotherapy or placebo). Efficacy was assessed by double-blind, placebo-controlled food challenge after 8 to 12 weeks of treatment. Blood samples were drawn for measurement of specific IgE, IgG(4), and serum cytokines before and after treatment., Results: Twenty-three patients were enrolled and divided into 2 treatment groups. Twenty-two patients reached the planned maximum dose at 4 days. Systemic reactions were observed in only 0.2% of the total doses administered. Mean hazelnut quantity provoking objective symptoms increased from 2.29 g to 11.56 g (P = .02; active group) versus 3.49 g to 4.14 g (placebo; NS). Moreover, almost 50% of patients who underwent active treatment reached the highest dose (20 g), but only 9% in the placebo. Laboratory data showed an increase in IgG(4) and IL-10 levels after immunotherapy in only the active group., Conclusion: Our data confirm significant increases in tolerance to hazelnut after sublingual immunotherapy as assessed by double-blind, placebo-controlled food challenge, and good tolerance to this treatment.

Background: There are few data on the long-term management of children with peanut/nut allergy. Advice is variable and often inadequate; further reactions are common. There is no consensus on the criteria for prescription of rescue medication, particularly adrenaline., Method: A longitudinal prospective and case-control study in a tertiary allergy clinic. Patients/parents/school staff of 747 children with confirmed peanut or tree nut allergy received detailed verbal and written advice on nut avoidance, training in recognition and (self-) treatment of reactions and a written treatment plan. The severity of nut allergy was graded (mild-severe) and emergency medication was allocated according to our criteria: all received oral antihistamines, injected adrenaline (EpiPen) was given to those with reactions with airway narrowing, milder reactions to low-dose exposure or concomitant asthma. At annual follow-up over 25 906 patient-months (median: 39 months) retraining was given and details of further reactions (frequency, severity and treatment) were obtained. Criteria for allocation of EpiPen were evaluated., Results: The worst reaction pre-enrolment was mild in 64% and moderate/severe in 36% (airway narrowing). Of 615 subjects followed up, 21% had a further reaction (eightfold reduction in frequency), mostly mild. There was a 60-fold reduction in the frequency of severe reactions. Of those with a moderate-severe initial reaction, 99.5% had no or a less severe follow-up reaction. No child with a mild or severe index reaction had a severe follow-up reaction. Only 1/615 (0.2%) had a severe follow-up reaction and only 2/615 (0.3%) used adrenaline, both successfully and had it available according to our criteria. Of mild-moderate reactions, 77% required oral antihistamines alone and 15% no treatment. Children who had follow-up reactions had more frequent and severe reactions pre-enrolment., Conclusion: The management plan greatly reduced the frequency and severity of further reactions and was successful for all children. Our criteria for selective prescription of EpiPen in the context of this management plan were appropriate. This is the first study to provide evidence on which to inform practice.