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.

Development of peanut, sesame and tree nut allergy in Polish children at high risk of food allergy: a protocol for a cross-sectional study.

INTRODUCTION: Peanut allergies cause serious health problems worldwide. A strong finding has shown that the early introduction of peanuts into the diet of infants at high risk of food allergy reduces the prevalence of peanut allergy. Allergies to peanuts, sesame and tree nuts have been shown to coexist in 60% of cases and vary according to geographical location and dietary habits. Insights into the prevalence of nut and seed allergies in societies with varying consumption levels are essential for developing population-specific weaning guidelines. Understanding the age at which peanut allergy develops is paramount for successful early introduction strategies. METHODS AND ANALYSIS: We will perform a cross-sectional study at two tertiary allergy centres in Warsaw and Bydgoszcz. Two hundred forty children aged 4-36 months with eczema or egg allergy will undergo an extensive assessment of their peanut, sesame and tree nut allergy status through skin testing, specific IgE measurements and oral food challenges. The primary outcome is the prevalence of peanut, sesame and tree nut allergies in Polish children at high risk of food allergy. Additionally, the timing of the development of peanut, sesame and tree nut allergies in the first 3 years of life in a high-risk population will be assessed. ETHICS AND DISSEMINATION: The Ethics Committee of the Medical University of Warsaw, Poland approved this protocol (KB/86/2021). The results of this study will be submitted to a peer-reviewed journal no later than 1 year after data collection. The abstract will be presented at relevant national and international conferences.Although the authors may be able to commit to journal submission no later than 1 year after data collection, publication dates remain beyond their control. TRIAL REGISTRATION NUMBER: NCT05662800.

Predictors of anaphylaxis to peanut and tree nuts in a Mediterranean population.

Background: Peanuts (PN) and tree nuts (TN) are major causes of anaphylaxis worldwide. We aimed to determine the clinical and demographic characteristics associated with anaphylaxis in patients sensitized to PN and/or TN in a Mediterranean population. Methods: We conducted a retrospective study, which included 198 patients allergic to PN and/or TN (allergy symptoms plus specific immunoglobulin E [sIgE] sensitization), evaluated in consultations from January 2015 to December 2020. Univariate analysis and multivariate logistic regression models were developed, including demographic, clinical, and laboratory data as independent variables, and anaphylaxis to each PN and/or TN as a dependent variables. Results: Anaphylaxis was associated with an earlier age of onset of allergy to PN, cashew and/or pistachio, and pine nut allergy but not to other TN allergies. Gender, atopic comorbidities, and cofactors were not associated with PN and/or TN anaphylaxis. Anaphylaxis to PN, cashew and/or pistachio, and pine nut were associated with reactivity to a fewer number of PN and/or TN foods. Although sIgE sensitization to lipid transfer proteins (LTP) was highly prevalent in our population, only seed storage protein (SSP) positivity was associated with anaphylaxis in PN allergy. The absence of pathogenesis-related protein family 10 sensitization correlated with PN and hazelnut anaphylaxis. A higher level of sIgE to almond extract predicted anaphylaxis but the level of sIgE to other PN and/or TN extracts did not predict it. Conclusion: The high prevalence of sensitization to the pan-allergen LTP did not seem to have a significant impact in PN and/or TN allergy severity in our study. Instead, other factors, such as early age of onset and positivity for SSPs, seem to strongly associate with anaphylaxis to specific PN and/or TN. These findings may contribute to individual risk assessment in these populations.

Tree nut allergy: a systematic review.

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.

Organ-specific symptom patterns during oral food challenge in children with peanut and tree nut allergy.

BACKGROUND: Peanut and tree nut allergies are common in childhood and often severe in nature. The clinical picture shows a wide variety of symptoms. OBJECTIVE: To analyze the distribution of clinical symptoms and severity during oral food challenges (OFC) in children. METHODS: Analysis of 1.013 prospectively recorded, positive OFCs with peanut (n = 607), hazelnut (n = 266), walnut (n = 97), and cashew (n = 43). Symptoms were categorized as immediate-type skin, gastrointestinal, upper and lower respiratory, cardiovascular symptoms, and eczema exacerbation. Symptom severity and treatment were recorded. RESULTS: Skin symptoms presented in 78%, followed by gastrointestinal (47%), upper (42%), and lower respiratory symptoms (32%). Cardiovascular symptoms presented in 6%. In three-quarter of the reactions, more than one organ was involved. Importantly, severe reactions occurred at every dose level. Peanut- and cashew-allergic patients had a higher relative risk of gastrointestinal symptoms compared with hazelnut- and walnut-allergic patients. Patients without vomiting had a 1.7 times higher risk developing immediate-type skin and/or lower respiratory symptoms. Three-quarter of the patients ever had eczema but worsening presented in only 10.5% of the OFCs. In patients with multiple food allergies, organs involved, eliciting dose and severity differed between allergens. CONCLUSION: Although comparisons between allergen groups with different clinical history, severity, comorbidities and laboratory data are difficult and might contain bias, our data confirm the high allergenic potential of peanut and tree nuts. The rare occurrence of eczema worsening emphasizes that avoidance diets of peanuts and tree nuts to cure eczema seem to be unnecessary and may hamper tolerance maintenance.

Onset of Nut Allergy in a Pediatric Cohort: Clinical and Molecular Patterns in the AFRUSEN Study.

BACKGROUND AND OBJECTIVE: Nut allergy is a growing problem, yet little is known about its onset in children. Objective: To characterize the onset of nut allergy in children in southern Europe. METHODS: The study population comprised consecutive patients up to 14 years of age who visited allergy departments with an initial allergic reaction to peanut, tree nut, or seed. The allergy work-up included a clinical history, food challenge, skin prick testing, determination of whole-extract sIgE, and ImmunoCAP ISAC-112 assay. RESULTS: Of the 271 children included, 260 were first diagnosed with nut allergy at a mean age of 6.5 years and at a mean (SD) of 11.8 (21.2) months after the index reaction. The most common culprit nuts at onset were walnut (36.5%), peanut (28.5%), cashew (10.4%), hazelnut (8.5%), pistachio (5.4%), and almond (5%). Onset of peanut allergy was more frequent in children ≤6 years and walnut in those aged >6 years (P=.032). In 65% of cases, the allergic reaction occurred the first time the patient consumed the nut, and 35% of reactions were anaphylactic. Overall, polysensitization to nuts was detected by skin prick testing in 64.9% of patients, although this rate was lower among walnut-allergic children (54.7%) and peanut-allergic children (54.1%) (P<.0001). Sensitization to 2S albumins was predominant (75%), especially Jug r 1 (52.8%), whereas sensitization to lipid transfer proteins was less relevant (37%). CONCLUSION: In the population we assessed, the onset of nut allergy occurred around 6 years of age, slightly later than that reported in English-speaking countries. Walnut was the main trigger, followed by peanut. 2S albumin storage proteins, especially Jug r 1, were the most relevant allergens. This study will help guide management and may contribute to preventive strategies in pediatric nut allergy.

Prevalence and early-life risk factors for tree nut sensitization and allergy in young adults.

BACKGROUND: Tree nut allergy may cause anaphylaxis. There are limited population-based studies on prevalence and early-life risk factors. METHODS: We evaluated the prevalence of reported symptoms and allergic sensitization to tree nuts at age 24 years in the BAMSE population-based cohort study and assessed early-life factors associated with the development of tree nut allergy. We estimated tree nut allergy prevalence, by analysing questionnaire data on tree nut ingestion and symptoms at age 12, 16 and 24 years, and IgE sensitization at age 24 years to hazelnut, walnut, pecan, cashew, pistachio, Brazil nut, almond extracts and allergen molecules Cor a 1, 9, 14 (hazelnut), Jug r 1 (walnut) and Ana o 3 (cashew). We evaluated eczema, asthma, food allergies, inherited risk of allergy and gender as potential early-life risk factors. RESULTS: Data were available for 2215/4089 (54%) BAMSE study participants, for estimation of the prevalence of tree nut sensitization (21.2%), tree nut allergy symptoms (9.8%) and combined sensitization and symptoms (7.9%, 2.1% for storage protein sensitization and symptoms, 4.3% for any sensitization and non-mild symptoms). Sixty-three per cent of sensitized individuals (295/470) were asymptomatic, but only 76/470 (16%) storage protein sensitized individuals. Egg allergy (ORadj 8.50 95% CI 2.15-33.6), eczema (ORadj 2.53 95% CI 1.21-5.32) and asthma (ORadj 5.59 95% CI 2.35-13.3)) at pre-school age were associated with future development of tree nut symptoms and storage protein sensitization. At age 24 years, tree nut allergy was associated with current eczema and with markers of current asthma severity. Sensitization to storage proteins was more strongly associated with symptoms than sensitization to whole extract for all tree nuts evaluated. CONCLUSIONS: In this Swedish cohort, we found tree nut whole extract sensitization is common but usually asymptomatic. Storage protein sensitization is a more reliable indicator of tree nut symptoms. Tree nut allergy is associated with early onset, persistent and severe atopic disease.

An Updated Overview of Almond Allergens.

Tree nuts are considered an important food in healthy diets. However, for part of the world's population, they are one of the most common sources of food allergens causing acute allergic reactions that can become life-threatening. They are part of the Big Eight food groups which are responsible for more than 90% of food allergy cases in the United States, and within this group, almond allergies are persistent and normally severe and life-threatening. Almond is generally consumed raw, toasted or as an integral part of other foods. Its dietary consumption is generally associated with a reduced risk of cardiovascular diseases. Several almond proteins have been recognized as allergens. Six of them, namely Pru du 3, Pru du 4, Pru du 5, Pru du 6, Pru du 8 and Pru du 10, have been included in the WHO-IUIS list of allergens. Nevertheless, further studies are needed in relation to the accurate characterization of the already known almond allergens or putative ones and in relation to the IgE-binding properties of these allergens to avoid misidentifications. In this context, this work aims to critically review the almond allergy problematic and, specifically, to perform an extensive overview regarding known and novel putative almond allergens.

Primary and pollen-associated hazelnut allergy in school-aged children in Germany: A birth cohort study.

BACKGROUND: Primary hazelnut allergy is a common cause of anaphylaxis in children, as compared to birch-pollen associated hazelnut allergy. Population-based data on hazelnut and concomitant birch-pollen allergy in children are lacking. We aimed to investigate the prevalence of primary and pollen-associated hazelnut allergy and sensitization profiles in school-aged children in Berlin, Germany. METHODS: 1570 newborn children were recruited in Berlin in 2005-2009. The school-age follow-up (2014-2017) was based on a standardized web-based parental questionnaire and clinical evaluation by a physician including skin prick tests, allergen specific immunoglobulin E serum tests and placebo-controlled double-blind oral food challenges, if indicated. RESULTS: 1004 children (63.9% response) participated in the school-age follow-up assessment (52.1% male). For 1.9% (n = 19, 95%-confidence interval 1.1%-2.9%) of children their parents reported hazelnut-allergic symptoms, for half of these to roasted hazelnut indicating primary hazelnut allergy. Symptoms of birch-pollen allergy were reported for 11.6% (n = 116 95%-CI 9.7%-13.7%) of the children. Both birch-pollen allergy and hazelnut allergy associated symptoms affected 0.6% (n = 6, 95%-CI 0.2%-1.3%) of children. Assessment of allergic sensitization was performed in 261 participants and showed that almost 20% of these children were sensitized to hazelnut, being the most frequent of all assessed food allergens, or birch-pollen, the majority to both. CONCLUSIONS: Based on parental reports hazelnut-allergic symptoms were far less common than sensitization to hazelnut. This needs to be considered by physicians to avoid unnecessary changes in diet due to sensitization profiles only, especially when there is a co-sensitization to hazelnut and birch-pollen.

Clinical Predictors and Outcomes of Oral Food Challenges Illustrate Differences Among Individual Tree Nuts.

BACKGROUND: Although allergy to tree nuts is often considered a single entity, there is heterogeneity in patient reactivity and immune response to different tree nuts. OBJECTIVE: We sought to characterize tree nut oral food challenges (OFCs) in a pediatric population performed at a single center over a 12-year period and determine differences in OFC outcome to different tree nuts. METHODS: A retrospective chart review was conducted in patients (0-20 years) who completed an unblinded OFC to any tree nut from 2007 to 2019 at Lurie Chlildren's Hospital of Chicago. Differences among almond, cashew, hazelnut, and walnut challenges were compared, and probability curves were used to estimate positive predictive values (PPVs) of specific IgE at OFC. RESULTS: A total of 531 tree nut OFCs were included. The mean age at OFC was 7.77 years (standard deviation, 4.33). Overall, 74.0% of children passed clinically indicated OFCs. Of the 4 most commonly challenged tree nuts, almost all patients passed OFC to almond (97.3%) and hazelnut (87.9%). Pass rates were lower for cashew (65.3%) and walnut (57.0%), P < .0001. The odds of failure were 0.83 times lower for patients who were avoiding without a previous reaction compared with those who had previously reacted (P = .0025). CONCLUSIONS: The majority of patients pass low-risk almond and hazelnut OFCs. PPVs at the 50th percentile for walnut (2.84 kU/L) and cashew (3.35 kU/L) were lower than those previous studies have suggested.

The influence of cultural attitudes to nut exposure on reported nut allergy: A pilot cross sectional study.

Food allergies in children have become a common management and diagnostic concern and have a significant influence on general health-related quality of life. We investigated the prevalence of reported nut allergy between populations with different cultural attitudes to nuts during pregnancy and infancy. We conducted a survey to investigate the relationship between cultural differences in the consumption of nuts during pregnancy, breastfeeding and exposure to nuts in early childhood against the reported prevalence of nut allergy between three populations: Libyan, UK Libyan and a general UK population. The survey was administered to a representative sample of UK and Libyan parents with children aged between 3 and 16 years who were asked to report prevalence of nut allergy and to describe the factors that might affect this such as cultural behaviours and diet. A total of 1,123 parents responded. Nut allergy was defined as an allergic reaction that required medical treatment. The reported rates of nut allergy showed a significant difference in nut allergy between the Libyan populations and the general UK population with an increased odds ratio of nut allergy of ~10 when comparing the Native Libyan population to the UK population. The UK Libyan population reported the same low rate of allergic reactions as the Libyan population which were both significantly lower than the UK population (p < .0001). The Libyan populations showed significant differences from the UK population in exposure to nuts during pregnancy, breastfeeding and early infancy. The development of peanut and almond allergy through tolerance induction could be prevented by frequent and early ingestion of a moderate quantity of nuts during infancy and by maternal ingestion during pregnancy or lactation.

Prevalence and natural history of tree nut allergy.

OBJECTIVE: Tree nuts are common causes of food-related allergic reactions and anaphylaxis. Resolution of tree nut allergy is thought to be low, yet studies of the natural history of tree nut allergy are limited. This review summarizes the available literature regarding tree nut allergy prevalence and natural history and discusses emerging diagnostic and prognostic developments that will inform clinical management of tree nut allergy. DATA SOURCES: A comprehensive literature search using PubMed was performed. STUDY SELECTIONS: Peer-reviewed publications relating to tree nut allergy prevalence, resolution, and diagnosis were selected, and findings were summarized using a narrative approach. RESULTS: Tree nut allergy prevalence varies by age, region, and food allergy definition, and ranges from less than 1% to approximately 3% worldwide. Reports on the natural history of tree nut allergy data are limited to retrospective clinical data or cross-sectional survey data of self-reported food allergy, with reported resolution ranging from 9% to 14%. Component-resolved diagnostics and basophil activation testing offer the potential to improve the diagnostic accuracy and predicted prognosis of specific tree nut allergy, but studies are limited. CONCLUSION: Tree nut allergy remains an understudied area of food allergy research with limited region-specific studies based on robust food allergy measures in population cohorts with longitudinal follow-up. This currently limits our understanding of tree nut allergy prognosis.

Tree Nuts Anaphylaxis in Preschool Age Children.

Summary: Introduction. The incidence of food-induced anaphylaxis (FIA) is increasing in young children. Although the commonest culprits are cow's milk and egg, FIA to tree nuts (TNs) have been increasing. Objective. Characterization of children referred to our allergy department due to TNs-induced anaphylaxis (TNs-FIA) during preschool age. Materials and methods. We have retrospectively included 25 children with clinical history of preschool TNs-FIA, proven by allergological work-up. TNs sensitization was assessed by skin prick tests and/or specific IgE. Results. The mean age of the first anaphylactic episode was 3.1±1.2 years. The majority (92%) had an allergic disease (52% asthma). The implicated TNs were cashew (11 children), walnut (8), pine nut (5), hazelnut (2) and almond (1). The reaction occurred after the first known ingestion in 68%. In 92%, symptoms appeared within 30 minutes after exposure. The most frequent clinical symptoms were mucocutaneous (96%), respiratory (80%) and gastrointestinal (52%). Twenty-one children were admitted to the emergency department, although only 48% were treated with epinephrine. An underneath IgE-mediated mechanism was proven in all cases. Immunologic cross-reactivity with other TNs was identified in 84%, and with peanut in 36%. Overall, in our center, TNs-FIA represents 18% of all causes of FIA. Conclusions. In preschool age children with TNs-FIA, cashew and walnut were the commonest implicated nuts. Most reactions occurred briefly after exposure to minimal amounts of TNs, demonstrating the high potency of these allergens. About one-third also had peanut sensitization. Potentially life-threatening TNs allergy can occur early in childhood and adequate management should be undertaken.

Phenotypical characterization of tree nuts and peanut allergies in east Mediterranean children.

INTRODUCTION/OBJECTIVES: The characteristics of tree nuts (TNs) and peanut (PN) allergies vary in different regions of the world. We aim to identify the characteristics of TNs/PN allergies in Turkish children. PATIENTS AND METHODS: A total of 227 children [4.8 (3.2-6.8) years] with TN and/or PN allergies were included. The phenotypical features of TNs/PN allergic children and the risk factors for multiple TNs/PN allergies were evaluated. RESULTS: Allergy to TNs/PN developed at a median age of 12.0 (10.0-18.0) months. The most common TNs/PN responsible for food allergies were the hazelnut (63.9%) and the pistachio (54.6%). Of TNs/PN allergic children, 54.2% experienced reactions with at least two types of . Current ages 6-10 years [OR:2.455, 95% CI:1.255-4.852, p=0.009] and family history of atopy [OR:2.156, 95% CI:1.182-3.932, p=0.012] were the risk factors for multiple TNs/PN allergies. Most of the patients with cashew nut and pistachio allergies exhibited co-sensitization and co-allergy to both of these TNs/PN. Although the rarest TNs/PN allergy was seen with almond, the possibility of allergy to other TNs or PN was highly increased in the patients with almond allergy compared to other TNs/PN. CONCLUSIONS: Children with TNs/PN allergy living in an East Mediterranean region differ from the counterparts living in Western countries by an earlier age of onset of the TNs/PN allergy symptoms, increasing possibility to have multiple TNs/PN allergy at older ages, and different spectrum of TN/PN allergies (hazelnut followed by pistachio/cashew) that all indicate the consumption habits which are important determinants of TN/PN allergy development.

Clinical and Molecular Characterization of Walnut and Pecan Allergy (NUT CRACKER Study).

BACKGROUND: Diagnostic methods for distinguishing walnut-allergic patients from walnut-sensitized but walnut-tolerant individuals are limited. Furthermore, characteristics of single walnut versus dual walnut-pecan allergy are lacking. OBJECTIVE: To provide clinical and molecular characteristics of walnut- and pecan-allergic patients. METHODS: A prospective cohort study of 76 walnut-sensitized patients was performed. Walnut skin prick test and serum measurements of specific IgE to walnut and its components were performed. Patients were challenged to walnut and pecan unless they regularly consumed walnut and pecan. RESULTS: Of the 76 patients studied, 61 were diagnosed as walnut-allergic and 15 as walnut-tolerant. IgE levels greater than or equal to 0.35 kUA/L to Jug r 1 or 4 provided the best diagnostic method for identifying walnut-allergic patients (accuracy, 0.93). Of the 61 walnut-allergic patients, 49 were pecan-allergic whereas 12 were pecan-tolerant. None of the walnut-tolerant patients was allergic to pecan. Dual allergic patients had significantly lower walnut reaction dose (median, 100 mg vs 1230 mg; P < .001). IgE levels greater than or equal to 0.35 kUA/L to Jug r 4, low-molecular-weight vicilins, or high-molecular-weight vicilins best segregated dual walnut-pecan-allergic patients from single walnut-allergic patients. Inhibition studies demonstrated that walnut pretreatment completely blocked IgE binding to pecan, whereas in some patients, pecan incubation only partially blocked IgE binding to walnut. CONCLUSIONS: Walnut components are helpful in diagnosing walnut allergy and in identifying patients with pecan coallergy. Competitive ELISA indicates that pecan comprises a subset of the allergenic determinants of walnut.

Food-induced anaphylaxis in infancy compared to preschool age: A retrospective analysis.

OBJECTIVE: Little is known regarding food anaphylaxis in infancy. We aimed to describe specificities of food anaphylaxis in infants (≤12 months) as compared to preschool children (1-6 years). METHODS: We conducted a retrospective study of all food anaphylaxis cases recorded by the Allergy Vigilance Network from 2002 to 2018, in preschool children focusing on infants. RESULTS: Of 1951 food anaphylaxis reactions, 61 (3%) occurred in infants and 386 (20%) in preschool children. Two infants had two anaphylaxis reactions; thus, we analyzed data among 59 infants (male: 51%; mean age: 6 months [SD: 2.9]); 31% had a history of atopic dermatitis, 11% of previous food allergy. The main food allergens were cow's milk (59%), hen's egg (20%), wheat (7%) and peanut (3%) in infants as compared with peanut (27%) and cashew (23%) in preschool children. Anaphylaxis occurred in 28/61 (46%) cases at the first cow's milk intake after breastfeeding discontinuation. Clinical manifestations were mainly mucocutaneous (79%), gastrointestinal (49%), respiratory (48%) and cardiovascular (21%); 25% of infants received adrenaline. Hives, hypotension and neurologic symptoms were more likely to be reported in infants than in preschool children (P = .02; P = .004; P = .002, respectively). Antihistamines and corticosteroids were more often prescribed in preschool children than in infants (P = .005; P = .025, respectively). CONCLUSION: Our study found that in infants presenting with their first food allergy, in a setting with a high rate of infant formula use, the most predominant trigger was cow's milk. As compared to older preschool children, hives, hypotonia and hypotension were more likely to be reported in infants. We believe that this represents a distinct food anaphylaxis phenotype that can further support developing the clinical anaphylaxis criteria in infants.