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.

IL-10-modulated dendritic cells from birch pollen- and hazelnut-allergic patients facilitate Treg-mediated allergen-specific and cross-reactive tolerance.

BACKGROUND: Approximately 70% of individuals allergic to birch pollen (Bet v 1.01 [Bet]) develop a secondary food allergy (e.g., hazelnut: Cor a 1.04 [Cor]), due to allergen cross-reactivity. However, standard immunotherapy for type I allergies often does not improve the food allergy sufficiently. We analyzed the allergen-specific and cross-reactive suppressive capacity of primary human regulatory T cells (Treg) induced by autologous IL-10-modulated dendritic cells (IL-10 DC) in vitro and in vivo. METHODS: CD4+ T cells of patients with birch pollen and associated hazelnut allergies were differentiated into Bet-specific or non-specific induced Treg (iTreg). After Bet- or Cor-specific restimulation the phenotype, proliferation, and suppressive capacity of iTreg subsets were analyzed. iTreg function was further investigated in humanized mouse models of airway and intestinal allergy, generated by engraftment of peripheral blood mononuclear cells from allergic donors into immunodeficient animals. RESULTS: After IL-10 DC priming and allergen-specific restimulation (Bet or Cor), non-specific control iTreg remained anergic, whereas Bet-specific iTreg proliferated extensively and exhibited a regulatory phenotype (enhanced expression of CTLA-4, PD-1, TNFR2, IL-10). Accordingly, activated Bet-specific iTreg displayed a high capacity to suppress Bet- and Cor-induced responder Th2 cell responses in vitro, indicating induction of both allergen-specific (birch) and cross-reactive tolerance (hazelnut). In vivo, the beneficial effect of Bet-specific iTreg was verified in humanized mouse models of allergic airway and intestinal inflammation, resulting in reduced allergen-induced clinical symptoms, and immune responses. CONCLUSION: Human IL-10 DC-induced iTreg facilitate allergen-specific and cross-reactive tolerance. Therefore, they are potential candidates for regulatory cell therapy in allergic and autoimmune diseases.

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

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

Current options in the management of tree nut allergy: A systematic review and narrative synthesis.

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.

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

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

Feasibility and Reaction Thresholds of Double-Blind, Placebo-Controlled Peanut and Nut Food Challenges Using Gingerbread Matrix.

INTRODUCTION: Double-blind, placebo-controlled food challenges are an important tool in diagnosing food allergies. PRACTALL recommends a dose-escalation schedule of 3-3,000 mg of food protein and a top dose of at least 2,000 mg to avoid false-negative results. This retrospective observational study tests the thresholds and feasibility using a previously published gingerbread matrix. METHODS: Data of food provocations with peanuts and nuts in children from 2015 to 2019 in the Reinier de Graaf Hospital were analyzed. We performed the food challenge following a schedule of 1, 3, 10, 30, 100, 300, 1,000, and 3,000 mg allergen protein. The feasibility of ingestion of the gingerbread matrix was determined by analyzing the amount of consumed gingerbread. RESULTS: 513 food challenges performed in 365 children (median age 6.9 years) were analyzed. Forty percent (204/513) of the food challenges were positive. Fifteen children already reacted at 1 mg protein (7%), 3 with a grade 3 reaction. The median cumulative amount of gingerbread matrix the children could eat on 1 day was 130.3 g. The median cumulative amount of allergen protein eaten was 2,585 mg; only 49% reached the minimum desired cumulative amount of 3,500 mg allergen protein. Despite that, there were no reported reactions at home in the 86% who introduced the allergen after a negative challenge. CONCLUSION: Seven percent of the children react on a starting dose of 1 mg of food protein. Therefore, when using the PRACTALL guidelines, early responders can be expected. Ingestion of a cumulative dose of 3,500 mg to reach a false-negative rate of maximum 5% is not feasible in most children using the gingerbread matrix. However, the cumulative dose may be reduced without increasing false-negative results, making challenges with the gingerbread matrix feasible for all age groups.

Expression, purification, characterization, and patient IgE reactivity of new macadamia nut iso-allergen.

Structural and functional information about food allergens is essential for understanding the allergenicity of food proteins. All allergens belong to a small number of protein families. Various allergens from different families have been successfully produced recombinantly in E. coli for their characterization and applications in allergy diagnosis and treatment. However, recombinant hexameric 11S seed storage protein has not been reported, although numerous 11S legumins are known to be food allergens, including the recently identified macadamia nut allergen Mac i 2. Here we report the production of a macadamia nut legumin by expressing it in E. coli with a substrate site of HRV 3C protease and cleaving the purified protein with HRV 3C protease. The protease divided the protein into two chains and left a native terminus for the C-terminal chain, resulting in a recombinant hexameric 11S allergen for the first time after the residues upstream to the cleavage site flipped out of the way of the trimer-trimer interaction. The 11S allergens are known to have multiple isoforms in many species. The present study removed an obstacle in obtaining homogeneous allergens needed for studying allergens and mitigating allergenicity. Immunoreactivity of the protein with serum IgE confirmed it to be a new isoform of Mac i 2.

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

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

Feasibility and safety of introducing cashew nut spread in infant diets-A randomized trial.

BACKGROUND: To reduce peanut allergy prevalence, infant feeding guidelines now recommend introducing peanuts in an age-appropriate form (such as peanut butter) as part of complementary feeding. However, due to a lack of randomized trial evidence, most infant feeding and food allergy prevention guidelines do not include tree nuts. The aims of this trial were to determine safety and feasibility of dosage consumption recommendations for infant cashew nut spread introduction. METHODS: This is a parallel, three-arm (1:1:1 allocation), single-blinded (outcome assessors), randomized controlled trial. General population term infants were randomized at 6-8 months of age to either a one teaspoon (Intervention 1 n = 59) or increasing dosage regime of one teaspoon at 6-7 months, two teaspoons at 8-9 months, and three teaspoons from 10 months of age onwards (Intervention 2 n = 67) cashew nut spread, both three times per week, or no specific advice on cashew introduction (Control n = 70). At 1 year of age, food challenge proven IgE-mediated cashew nut allergy was assessed. RESULTS: Compliance in Intervention 1 (92%) was higher than Intervention 2 (79%), p = .04. Only one infant had delayed (at 5 h) facial swelling and eczema flare to cashew introduction at 6.5 months, but no cashew allergy at 1 year. Only one infant (Control) had cashew allergy at 1 year, and this infant had not been introduced to cashew prior to 12 months of age. CONCLUSION: Regular infant consumption of one teaspoon of cashew nut spread three times per week from 6 to 8 months of age was found to be feasible and safe.

Citrin: a novel food allergen in citrus seeds and citrus-derived pectin that shows cross-reactivity with cashew and pistachio.

BACKGROUND: Patients exquisitely sensitive to cashew/pistachio are at risk for allergic reactions to citrus seeds and pectin. OBJECTIVE: In this study, we sought to evaluate whether pectin is contaminated with citrus seeds, to identify a culprit antigen in citrus seeds, and to assess for cross-reactivity among allergens in citrus seeds, citrus pectin, and cashew or pistachio. METHODS: Proteins from orange seed coats, orange seed endosperms, lemon seeds, grapefruit seeds, citrus pectin, apple pectin, and grapefruit pectin were extracted. Protein concentrations in all extracts were determined and visualized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis technique. Immunoglobulin E-binding capacity was determined with Western blot analyses and tandem mass spectrometry for the identification of the culprit allergen in citrus seeds and pectin. RESULTS: In subjects with citrus seed, pectin, and cashew allergies, there was strong immunoglobulin E-reactivity to bands between 17 to 28 kDa and 28 to 38 kDa. The tandem mass spectrometry analysis of these bands indicated the presence of citrin as the culprit allergen. Citrin and Ana o 2 are both 11S globulins belonging to the cupin superfamily, and significant homology was found between these proteins. CONCLUSION: Citrus pectin may be contaminated with citrus seeds. Citrin, a newly identified allergen in citrus seeds, seems to be the culprit antigen in citrus seeds and contaminated citrus pectin. Citrin is highly homologous with Ana o 2 in cashew and Pis v 2 in pistachio, suggesting potential for cross-reactivity and providing an explanation for co-allergenicity of cashew or pistachio, citrus seeds, and citrus pectin.

Identification and Structure of Epitopes on Cashew Allergens Ana o 2 and Ana o 3 Using Phage Display.

BACKGROUND: Cashew (Anacardium occidentale L.) is a commercially important plant. Cashew nuts are a popular food source that belong to the tree nut family. Tree nuts are one of the eight major food allergens identified by the Food and Drug Administration in the USA. Allergies to cashew nuts cause severe and systemic immune reactions. Tree nut allergies are frequently fatal and are becoming more common. AIM: We aimed to identify the key allergenic epitopes of cashew nut proteins by correlating the phage display epitope prediction results with bioinformatics analysis. DESIGN: We predicted and experimentally confirmed cashew nut allergen antigenic peptides, which we named Ana o 2 (cupin superfamily) and Ana o 3 (prolamin superfamily). The Ana o 2 and Ana o 3 epitopes were predicted using DNAstar and PyMoL (incorporated in the Swiss-model package). The predicted weak and strong epitopes were synthesized as peptides. The related phage library was built. The peptides were also tested using phage display technology. The expressed antigens were tested and confirmed using microtiter plates coated with pooled human sera from patients with cashew nut allergies or healthy controls. RESULTS: The Ana o 2 epitopes were represented by four linear peptides, with the epitopes corresponding to amino acids 108-111, 113-119, 181-186, and 218-224. Furthermore, the identified Ana o 3 epitopes corresponding to amino acids 10-24, 13-27, 39-49, 66-70, 101-106, 107-114, and 115-122 were also screened out and chosen as the key allergenic epitopes. DISCUSSION: The Ana o 3 epitopes accounted for more than 40% of the total amino acid sequence of the protein; thus, Ana o 3 is potentially more allergenic than Ana o 2. CONCLUSIONS: The bioinformatic epitope prediction produced subpar results in this study. Furthermore, the phage display method was extremely effective in identifying the allergenic epitopes of cashew nut proteins. The key allergenic epitopes were chosen, providing important information for the study of cashew nut allergens.

Measurement of IgE to hazelnut allergen components cannot replace hazelnut challenge in Dutch adults.

BACKGROUND: Component-resolved diagnostics (CRD) help predict hazelnut allergy (HA) in children, but are of unknown diagnostic value in adults. This study aimed to evaluate the diagnostic accuracy of IgE to hazelnut extract and components in adults. METHODS: A Dutch population of consecutively presenting adults suspected of HA, who underwent a double-blind placebo-controlled food challenge, were included. Serum IgE to hazelnut extract and Cor a 1, 8, 9, and 14 was measured on ImmunoCAP. Diagnostic accuracy was assessed by area under the curve (AUC) analysis. RESULTS: Of 89 patients undergoing challenge, 46 had challenge-confirmed HA: 17 based on objective and 29 based on subjective symptoms. At commonly applied cutoffs 0.1 and 0.35 kUA /L, high sensitivity was observed for IgE to hazelnut extract and Cor a 1 (range 85-91%), and high specificity for IgE to Cor a 8, 9 and 14 (range 77-95%). However, the AUCs for hazelnut extract and components were too low for accurate prediction of HA (range 0.50-0.56). Combining hazelnut extract and component IgE measurements did not significantly improve accuracy. Higher IgE levels to Cor a 9 and 14 were tentatively associated with HA with objective symptoms, but the corresponding AUCs still only reached 0.68 and 0.63, respectively. CONCLUSIONS: Although hazelnut allergic adults are generally sensitized to hazelnut extract and Cor a 1, and hazelnut tolerant adults are usually not sensitized to Cor a 8, 9, or 14, challenge testing is still needed to accurately discriminate between presence and absence of HA in adults from a birch-endemic country.

Cashew oral immunotherapy for desensitizing cashew-pistachio allergy (NUT CRACKER study).

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.

Tree nut introduction in a peanut-allergic child: To eat, to screen, or to avoid?

There is no defined standard of care around tree nut introduction in a peanut-allergic child, and the role of screening prior to tree nut introduction is controversial. There is some evidence that peanut-allergic children are at increased risk of tree nut allergy, with approximately 23-68% of children with co-existent peanut/tree nut allergy. In some studies, it has been shown that tree nut allergy in children has the potential to be a severe allergy. However, this appears to be age-specific as infant anaphylaxis in general tends to be milder, and there has been no fatality reported on the first ingestion of an allergen in infancy. Familial hesitancy has been identified as a possible condition for undertaking screening tests prior to allergen introduction. Indeed, there has been limited evidence that caregiver hesitancy may exist in peanut-allergic families with tree nut introduction. However, pre-emptive screening has the potential to overdiagnose tree nut allergy and delay introduction (which could paradoxically increase risk). As a result, the decision is best made in the context of shared decision-making and patient preference-sensitive care.

Ana o 3 sIgE testing increases the accuracy of cashew allergy diagnosis using a two-step model.

BACKGROUND: Measurement of cashew-specific IgE (sIgE) is often used to confirm sensitization but does not reliably diagnose clinical allergy. Ana o 3 is the dominant cashew allergen detected in 75-100% of patients with cashew allergy but not currently used in clinical practice. OBJECTIVES: To determine if component-resolved diagnostics using specific IgE to the 2 S albumin from cashew, Ana o 3, improves the accuracy of diagnosing cashew allergy, thereby circumventing the need for an oral food challenge (OFC) in some patients. METHODS: A population-based sample of 5276 children was recruited at age 1 year and followed up at age 6 years. Children with positive cashew skin prick test at age 6 underwent an OFC to clarify allergy status. Forty-seven children (mean age 5.02 ± 0.2) (33 cashew-allergic and 14 cashew-tolerant) had cashew sIgE and Ana o 3 sIgE quantified by ImmunoCAP System FEIA. RESULTS: A cutoff of >0.32 kUA/L for Ana o 3 sIgE provided 95% specificity and 90% sensitivity and correctly identified 90% of clinical cashew allergy. At the same specificity, the sensitivity for cashew sIgE (>8.5 kUA/L) was only 26%. Sequential measurement of cashew sIgE followed by Ana o 3 sIgE diagnosed 90% of children with cashew allergy without the need for an OFC. CONCLUSION: Ana o 3 sIgE testing provides higher diagnostic accuracy than cashew sIgE. Sequential measurement of cashew sIgE followed by Ana o 3 removed the need for a food challenge from 66% down to 12.8% (5-fold) of children compared with cashew sIgE testing alone.

Macadamia nut-specific IgE levels for predicting anaphylaxis.

BACKGROUND: Despite the high risk of anaphylaxis in patients with a macadamia nut allergy (MdA), little is known about the significance of macadamia nut-specific immunoglobulin E (Md-sIgE). Thus, this study aimed to investigate the utility of Md-sIgE for predicting anaphylaxis. METHODS: Children with suspected MdA who visited our hospital were included. MdA was defined as either failing the 3-g macadamia nut (Md) oral food challenge (OFC) or confirming obvious immediate symptoms following Md ingestion. Non-MdA was defined as passing the 3-g Md OFC. RESULTS: A total of 41 children (29 [71%] males) with a median age of 7.7 years were included. The median Md-sIgE level was 2.23 kUA /L. Among the 21 children diagnosed with MdA, eight and 13 children did (An group) and did not (non-An group) develop anaphylaxis. Twenty children were included in the non-MdA group. The Md-sIgE level was significantly higher in the An group relative to the others (7.97 vs. 1.92 kUA /L, p < .001). Furthermore, the Md-sIgE level was significantly higher in the An group than in the non-An group (7.97 vs. 1.92 kUA /L, p = .02). However, there was no significant difference in the Md-sIgE between the non-An and non-MdA groups (1.92 vs. 1.90 kUA /L, p > .99). The area under the curve for predicting anaphylaxis in Md-sIgE was 0.92 (95% CI: 0.83-1.00), and the optimal cut-off value was 3.76 kUA /L. CONCLUSION: Md-sIgE levels were useful in predicting anaphylaxis. Above the cut-off value, we emphasize paying careful attention to the risk of anaphylaxis.

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.

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.

Optimizing tools for evaluating challenge outcomes in children with cashew nut allergy.

BACKGROUND: The incidence of cashew nut anaphylaxis is increasing and there is a need for accurate diagnostic tests. Age-specific cutoffs in children are lacking. Changes in serum tryptase levels are not well documented in pediatric food allergy, except in anaphylaxis. OBJECTIVE: To evaluate the ability of various tests to diagnose cashew nut allergy and to predict reaction severity. We also investigated changes in tryptase and their correlation to reaction severity. METHODS: We performed an open cashew nut challenge on 106 children (aged 1-16 years), who were sensitized to cashew nut with either previous allergic reaction to cashew nut or no known exposure. We analyzed the accuracy of Ana o 3 immunoglobulin E (IgE), cashew nut IgE, skin prick test, basophil activation test (BAT), and combinations thereof to diagnose cashew nut allergy and to predict reaction severity. Tryptase level was measured at the baseline and during an allergic reaction. RESULTS: A total of 72 children had positive challenge outcomes. Ana o 3 IgE seemed to be the best single test to diagnose cashew allergy, with a 0.97 kU/L cutoff exhibiting 94.1% specificity and 61.1% sensitivity. Though BAT values of at least 22.8% best predicted reaction severity, with 91.7% specificity and 60.7% sensitivity, the cutoffs were age-specific. Tryptase levels increased substantially 1 to 2 hours after the first allergic symptoms compared with baseline. CONCLUSION: Ana o 3 IgE seems to be the best diagnostic test in pediatric cashew nut allergy, and test combinations do not seem to improve the diagnostics. Cutoffs are age-specific. BAT is promising in predicting reaction severity. Tryptase levels should be measured 1 to 2 hours after initiation of an allergic reaction.

Characteristics of patients with spontaneous resolution of sesame allergy.

BACKGROUND: The prevalence of sesame allergy is increasing; strict avoidance is the mainstay of therapy. Lately, sesame oral immunotherapy was presented as an alternative treatment, with a high rate of success. Therefore, data on the natural history and the clinical characteristics of patients with persistent sesame allergy are important for the management of patients with sesame allergy. OBJECTIVE: To describe the natural history of patients with sesame allergy and the clinical characteristics of patients with spontaneous resolution of sesame allergy compared with patients with persistent sesame allergy. METHODS: In our retrospective study, electronic health records of patients with sesame allergy diagnosis were reviewed for demographic and clinical data. Statistical analysis of clinical characteristics of patients with spontaneous resolution compared with persistent sesame allergy was performed. RESULTS: A total of 190 patients with sesame allergy were followed for 3.86 ±4.43 years. Of these patients, 61 (32.1%) had spontaneous resolution of sesame allergy. Patients with mild, early (before the age of 10 months) first sesame allergic reaction, with smaller than 7-mm skin prick test and without concomitant tree nut allergy had better resolution rate (56.1%). CONCLUSION: Sesame allergy spontaneously resolved in approximately one-third of our patients and in more than half of the patients with mild first reaction (grade 1) at a young age (<10 months), with small skin prick test (<7 mm) and no concomitant tree nut allergy. Larger prospective studies with longer follow-up period are needed to better characterize the sesame allergic patients with persistent allergy who may need oral immunotherapy.