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.

Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient clinic survey.

BACKGROUND: Hazelnut allergy is birch pollen-driven in Northern/Western Europe and lipid transfer protein-driven in Spain and Italy. Little is known about other regions and other allergens. OBJECTIVE: Establishing a molecular map of hazelnut allergy across Europe. METHODS: In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP. RESULTS: Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen-driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium, plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen. CONCLUSIONS: In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established.

Sensitization to Cor a 9 and Cor a 14 is highly specific for a hazelnut allergy with objective symptoms in Dutch children and adults.

BACKGROUND: Component-resolved diagnosis has been shown to improve the diagnosis of food allergy. OBJECTIVE: We sought to evaluate whether component-resolved diagnosis might help to identify patients at risk of objective allergic reactions to hazelnut. METHOD: A total of 161 hazelnut-sensitized patients were included: 40 children and 15 adults with objective symptoms on double-blind, placebo-controlled food challenges (DBPCFCs) and 24 adults with a convincing objective history were compared with 41 children and 41 adults with no or subjective symptoms on DBPCFCs (grouped together). IgE levels to hazelnut extract and single components were analyzed with ImmunoCAP. RESULTS: IgE levels to hazelnut extract were significantly higher in children with objective than with no or subjective symptoms. In 13% of children and 49% of adults with hazelnut allergy with objective symptoms, only sensitization to rCor a 1.04 was observed and not to other water-soluble allergens. Sensitization to rCor a 8 was rare, which is in contrast to rCor a 1. Sensitization to nCor a 9, rCor a 14, or both was strongly associated with hazelnut allergy with objective symptoms. By using adapted cutoff levels, a diagnostic discrimination between severity groups was obtained. IgE levels to either nCor a 9 of 1 kUA/L or greater or rCor a 14 of 5 kUA/L or greater (children) and IgE levels to either nCor a 9 of 1 kUA/L or greater or rCor a 14 of 1 kUA/L or greater (adults) had a specificity of greater than 90% and accounted for 83% of children and 44% of adults with hazelnut allergy with objective symptoms. CONCLUSION: Sensitization to Cor a 9 and Cor a 14 is highly specific for patients with objective symptoms in DBPCFCs as a marker for a more severe hazelnut allergic phenotype.

Clinical thresholds to egg, hazelnut, milk and peanut: results from a single-center study using standardized challenges.

BACKGROUND: Large studies of individual thresholds and risk profiles for foods are sparse. Previous reports indicate that thresholds adjusted for the protein content in foods would be comparable. OBJECTIVE: To establish and compare clinical threshold values for egg, hazelnut, milk and peanut, and correlating them to severity of symptoms. METHODS: Seven hundred eighty-one challenges were performed in 487 patients (age range, 0.5-73.5 years). Using interval censoring survival analysis, the dose distribution of thresholds was fitted to a log-normal function. Symptom score was correlated to thresholds. RESULTS: Based on the 405 challenges resulting in objective signs, similar distribution of thresholds for hazelnut, milk, and peanut challenges were found, whereas individuals with egg allergy were bimodally distributed with a high or a low threshold. Eliciting dose in 10% (95% confidence interval) was 42.9 (24-76.8) mg whole eggs, 133.8 (95.9-186.6) mg whole hazelnut, 106.5 (59.7-190.6) mg roasted peanut, and 2.9 (1.5-5.4) mL milk. Adults showed more severe symptoms and signs than children, and peanut caused more severe reactions than the 3 other foods. CONCLUSION: Thresholds for the different foods were not comparable, and eliciting dose for the 4 foods differed, even if adjusted for protein content. Increasing age but not a low threshold dose is associated with severe symptoms on challenge. Peanuts elicit more severe reactions than the other foods.

A qualitative study of families of a child with a nut allergy.

OBJECTIVES: The aim of this study was to explore, using qualitative methods, the experiences of children and their parents living with nut allergy. METHODS: Children with a confirmed diagnosis of peanut allergy were identified from a database of patients maintained at an allergy clinic at a large teaching hospital. Interviews with 26 families were conducted involving 11 children, 25 mothers and 12 fathers. RESULTS: The diagnosis of nut allergy signalled a critical transition-or biographical disruption-in the life of the family. Parents took on the role of 'alert assistant' and sought to create 'safe places' where nuts were not permitted, but often struggled when outside the home environment. The option of 'passing as normal', often used by people with a chronic illness to avoid stigma, was not available to them. Consequently, parents often reported being treated as faddy, demanding, and neurotic, and children suffered from teasing and exclusion. The social consequences of nut allergy were worsened by poor labelling and control of foods and products containing nuts. DISCUSSION: In many ways, nut allergy may be considered a form of disability, because it imposes social barriers on participating fully in society.

Management of nut allergy influences quality of life and anxiety in children and their mothers.

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.

Impact of native, heat-processed and encapsulated hazelnuts on the allergic response in hazelnut-allergic patients.

BACKGROUND: Pollen-associated food allergy is common. However, systemic reactions or even life-threatening anaphylaxis are rare. OBJECTIVE: The aim of this study was to investigate the clinical impact of native, heat-processed and encapsulated hazelnuts (HN) in patients with proven HN allergy. METHODS: One hundred and thirty-two patients with a positive history of HN allergy were recruited. Sensitization was confirmed by a skin prick test (SPT) and sIgE against HN. After an HN-free diet, double-blind placebo-controlled challenges were performed with increasing amounts of native and roasted HN. A subset of patients were given HN capsules to circumvent the oral mucosa. Basophil activation was measured by flow cytometry before and after provocation but also ex vivo using native and roasted HN extracts. RESULTS: Three groups of HN-allergic patients were identified depending on their clinical reaction pattern. The dosages by which allergic reactions were elicitated varied for native HN from 0.01 to 2.0 g, with a median of 0.1 g, for roasted HN from 0.01 to 10.0 g, with a median of 0.23 g, and for encapsulated HN from 0.1 to 3.0 g, with a median of 0.3 g. Accordingly, the SPT was more frequently positive and resulted in greater weal reactions if native HN was used. This finding was confirmed by ex vivo basophil activation showing that significantly higher allergen extract concentrations (roasted>native) were necessary to induce 50% basophil activation. CONCLUSION: Our data show that heat processing of HN reduces its allergenicity. SPT but also the basophil activation test can be used to determine the reactivity of an allergen extract.

Hazelnut allergy: from pollen-associated mild allergy to severe anaphylactic reactions.

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 allergy in childhood.

Peanut and tree nut allergies present multiple challenges in their presentation and management. These challenges have become increasingly relevant in recent years, as these allergies appear to have become more common. An estimated 1-2% of the population in the USA is allergic to peanut or tree nuts. Peanut allergy typically presents with symptoms in one of the first few exposures to peanut. Diagnosis is based on clinical history along with skin prick test, or quantitation of allergen-specific immunoglobulin E (IgE), and oral food challenges when indicated. Once the diagnosis is confirmed, the only current management approach is strict avoidance of the food. This is clearly an imperfect option as it can be difficult to avoid completely peanut and tree nuts and accidental exposures are not uncommon. Only about 20% of those with peanut allergy, and <10% of those with tree nut allergy, are reported to acquire tolerance. Additionally, peanut allergy can recur, with one study finding a recurrence rate of 8%. Peanut and tree nuts are the foods most frequently associated with fatal episodes of anaphylaxis. This is of particular concern in adolescents and young adults, among whom life-threatening and fatal food allergy-related reactions are most common.

Differences in allergenic potential of food extracts following oral exposure in mice reflect differences in digestibility: potential approaches to safety assessment.

An animal model for food allergy is needed to assess genetically modified food crops for potential allergenicity. The ideal model must produce allergic antibody (IgE) to proteins differentially according to known allergenicity before being used to accurately identify potential allergens among novel proteins. The oral route is the most relevant for exposure to food antigens, and a protein's stability to digestion is a current risk assessment tool based on this natural route. However, normal laboratory animals do not mount allergic responses to proteins administered orally due to oral tolerance, an immunologic mechanism which specifically suppresses IgE. To circumvent oral tolerance and evoke differential IgE responses to a panel of allergenic and nonallergenic food extracts, female C3H/HeJ mice were exposed subcutaneously or orally with cholera toxin as an adjuvant. All foods elicited IgE by the subcutaneous route. Oral exposure, however, resulted in IgE to allergens (peanut, Brazil nut, and egg white) but not to nonallergens (spinach and turkey), provided that the dose and exposures were limited. Additionally, in vitro digestibility assays demonstrated the presence of digestion-stable proteins in the allergenic food extracts but not in the nonallergenic foods. Our results suggest that the subcutaneous route is inadequate to distinguish allergens from nonallergens, but oral exposure under the appropriate experimental conditions will result in differential allergic responses in accordance with known allergenicity. Moreover, those foods containing digestion-resistant proteins provoke allergic responses in this model, supporting the current use of pepsin resistance in the decision tree for potential allergenicity assessment.

Lipid transfer protein-linked hazelnut allergy in children from a non-Mediterranean birch-endemic area.

BACKGROUND: Hazelnut allergy in birch pollen-exposed areas is usually due to cross-reactivity (Cor a 1 and 2) and is usually mild in nature (oral allergy). In areas without birches, severe reactions are more prevalent and linked to sensitization to the lipid transfer protein (LTP) Cor a 8. OBJECTIVE: We sought to investigate whether sensitization to LTP plays a role in more severe (objective) hazelnut-induced symptoms in children from a birch-endemic area. METHODS: Sensitization to Cor a 8, Cor a 2, Cor a 1, and Bet v 1 was determined by means of RASTs and immunoblotting in hazelnut-sensitized children with (n = 8) and without (n = 18) objective reactions during double-blind, placebo-controlled food challenges. Additionally, samples from 191 hazelnut-sensitized nonchallenged children were analyzed. RESULTS: Children with objective reactions during double-blind, placebo-controlled food challenge had higher IgE titers to hazelnut (P < .001) and recognized more allergens on immunoblotting (P = .001) than those without such reactions. All children with objective symptoms were sensitized to Cor a 8 (0.51-23.3 IU/mL) compared with only 1 child without objective reactions (0.90 IU/mL). In a multivariate analysis only IgE against Cor a 8 remained as an independent risk factor (undefined odds ratio; P < .0001). In the group of nonchallenged children (n = 191), the prevalence of LTP sensitization was greater than 30%. Unexpectedly, sensitization to Cor a 1 was observed in children not sensitized to Bet v 1. CONCLUSION: Sensitization to hazelnut LTP is a risk factor for objective symptoms in children from a birch-endemic area.

The natural history of peanut and tree nut allergy.

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.

The natural history of tree nut allergy.

BACKGROUND: Although 20% of children outgrow peanut allergy, the natural history of tree nut (TN) allergy has not been well studied. OBJECTIVE: The goals of the study were to estimate the proportion of children who outgrow TN allergy and examine predictors of outgrowing it. METHODS: Patients with TN allergy, defined as a history of reaction on ingestion and evidence of TN-specific IgE (TN-IgE) or positive TN-specific IgE level but no history of ingestion, were evaluated. If all current TN-IgE levels were less than 10 kilounits of antibody (kU(A))/L, double-blind, placebo-controlled food challenges were offered. Patients who had undergone open TN challenges as part of routine clinical care were also included. RESULTS: Two hundred seventy-eight patients with TN allergy were identified. One hundred one (36%) had a history of acute reactions, 12 (12%) of whom had reactions to multiple TNs and 73 (63%) of whom had a history of moderate-to-severe reactions. Nine of 20 patients who had previously reacted to a TN passed challenges, so that 9 (8.9%; 95% CI, 4% to 16%) of 101 patients with a history of prior TN reactions outgrew TN allergy. Fourteen of 19 who had never ingested TNs but had detectable TN-specific IgE levels passed challenges. One hundred sixty-one did not meet the challenge criteria, and 78 met the criteria but declined challenges. Looking at specific TN-IgE cutoffs, 58% with TN-IgE levels of 5 kU(A)/L or less and 63% with TN-IgE levels of 2 kU(A)/L or less passed challenges. CONCLUSIONS: Approximately 9% of patients outgrow TN allergy, including some who had prior severe reactions. Although ideal cutoffs for challenge cannot be firmly recommended on the basis of these data, patients aged 4 years or older with all TN-IgE levels of 5 kU(A)/L or less should be considered for challenge.

Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans.

BACKGROUND: Hazelnut allergy can be a consequence of sensitization to cross-reactive pollen, especially from the Fagales family. However, severe allergic reactions after ingestion of hazelnuts without associated pollen allergy have been reported. In these cases, oral sensitization by hazelnut ingestion is plausible. OBJECTIVE: We have reported that antiulcer drugs promote oral sensitization to digestion-labile food allergens. Because hazelnut proteins were sensitive to gastric digestion in our in vitro assay, we aimed to analyze the effect of antiulcer treatment on oral sensitization to hazelnut proteins. DESIGN: BALB/c mice were fed hazelnut extract with or without antiulcer drugs. In parallel, gastroenterologic patients (n = 153) were screened during antiulcer treatment for specific immunoglobulin (Ig) E to hazelnut and inhalative allergens in vitro and in vivo. RESULTS: Mice fed hazelnut extract in combination with antiulcer drugs formed anaphylactogenic IgG1 toward hazelnut and developed type I skin reactivity to hazelnut extract. In the human study population, 5 of 153 (3.3%) patients developed hazelnut-specific IgE, 4 of 5 developed specific skin reactivity, 3 of 5 had a positive result to oral provocation, and 2 of 5 manifested a food allergy to hazelnut after a 3-mo course of antiulcer treatment. Immunoblot testing with recombinant allergens showed that hazelnut, but not Fagales pollen, was the genuine elicitor in mice and humans. CONCLUSION: Our experimental and epidemiologic data suggest that the intake of antiulcer drugs may lead to the induction of immediate-type food hypersensitivity toward hazelnut.

Sudden death associated with food and exercise.

Exercised-induced anaphylaxis occurs in conjunction with significant physical exertion. Anaphylaxis occurring when an individual exercise within a few hours of ingesting a particular food is an unusual variant. Cardiovascular symptoms can be the sole manifestation of exercise-induced food allergies, in which case death may mimic sudden cardiac death during physical exertion due to other pathologic causes. We report the sudden and unexpected death of an individual following the ingestion of hazelnuts and almonds, to which the individual was not previously known to be allergic. The decedent collapsed during vigorous dancing. The death was not associated with cutaneous or laryngeal manifestations of anaphylaxis. Awareness of the variable manifestations of food-precipitated anaphylaxis is necessary to correctly establish the diagnosis. An elevated serum tryptase level may be indicative of an allergic reaction, and allergen-specific IgE levels may be used to confirm the particular antigen.

Tree nut allergy.

Tree nuts are clinically associated with severe immunoglobulin E-mediated systemic allergic reactions independent of pollen allergy and with reactions that are usually confined to the oral mucosa in patients with immunoglobulin E directed toward cross-reacting pollen allergens. The latter reactions can progress to severe and life-threatening episodes in some patients. Many patients with severe tree nut allergy are co-sensitized to peanut. Clinical studies on cross-reactivity between the tree nuts are few in number, but based on reports to date, avoidance of the other tree nuts once sensitivity is diagnosed appears prudent unless specific challenges are performed to ensure clinical tolerance. Even then, great care must be taken to avoid cross-contamination. As with other severe food allergies, a recurrent problem in clinical management is the failure of physicians to prescribe self-injectable epinephrine to patients who are at risk of anaphylaxis.