Altered immune cell profiles and impaired CD4 T-cell activation in single and multi-food allergic adolescents.

BACKGROUND: Approximately 5% of adolescents have a food allergy, with peanut and tree nut allergies the most common. Having two or more food allergies in adolescence also doubles the risk of any adverse food reaction, and is associated with increased dietary and social burden. Investigations of immune function in persistently food allergic children are rare. OBJECTIVE: In the present study, we aimed to investigate the immune mechanisms that underlie food allergy in adolescence. METHODS: We used high-dimensional flow cytometry, unsupervised computational analysis and functional studies to comprehensively phenotype a range of non-antigen-specific immune parameters in a group of well-characterized adolescents with clinically defined single peanut allergy, multi-food allergy and aged-matched non-food allergic controls. RESULTS: We show that food allergic adolescents have higher circulating proportions of dendritic cells (p = .0084, FDR-adjusted p = .087, median in no FA: 0.63% live cells, in FA: 0.93%), and higher frequency of activated, memory-like Tregs relative to non-food allergic adolescents (p = .011, FDR-adjusted p = .087, median in no FA: 0.49% live cells, in FA: 0.65%). Cytokine profiling revealed that CD3/CD28 stimulated naïve CD4 T cells from food allergic adolescents produced less IL-6 (p = .0020, FDR-adjusted p = .018, median log2 fold change [stimulated/unstimulated] in no FA: 3.03, in FA: 1.92) and TNFα (p = .0044, FDR-adjusted p = .020, median in no FA: 9.16, in FA: 8.64) and may secrete less IFNγ (p = .035, FDR-adjusted p = .11, median in no FA: 6.29, in FA: 5.67) than naïve CD4 T cells from non-food allergic controls. No differences between clinical groups were observed for LPS-stimulated monocyte secretion of cytokines. CONCLUSIONS: These results have important implications for understanding the evolution of the immune response in food allergy throughout childhood, revealing that dendritic cell and T-cell signatures previously identified in early life may persist through to adolescence.

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.

[Kounis syndrome - allergic myocardial infarction. a case report].

Kounis syndrome or allergic myocardial infarction is an acute coronary syndrome in the course of an allergic reaction. In allergic patients in response to a specific condition - nourishment, inhalation, environmental substances, drug or insect bite there is an allergic reaction involving many different cells and mediators that can cause coronary artery spasm or initiate the process of rupture and activation of atherosclerotic plaque resulting in acute coronary syndrome. The paper describes a case of a young man with allergy to pollen and confirmed sensitization to nuts, who developed a full-blown anaphylactic shock after eating the nut mix and experienced a rapidly passing acute coronary syndrome with troponin up to 4.7 µg/L. An increased concentration of tryptase (15 µg/L), total IgE (> 3,000 IU/mL) and specific anti-nut IgE (55.1 kUA/L) were found. Based on the course of the disease and the results of allergic and cardiac tests, allergic type 1 myocardial infarction, i.e. caused by coronary artery spasm, was diagnosed. During the hospitalization, the patient's condition improved quickly and after a few days he left the hospital without the signs of permanent damage to the heart muscle.

Risk Factors and Clinical Features in Cashew Nut Oral Food Challenges.

BACKGROUND: Cashew nuts (CN) are capable of causing severe allergic reactions. However, little has been reported about the details of CN oral food challenges (OFC). METHODS: CN-specific IgE (sIgE) levels were measured for 1 year in 66 patients who underwent an OFC with >3 g CN for diagnosis or confirmation of tolerance acquisition between June 2006 and August 2014. We retrospectively analyzed the OFC and patient background. RESULTS: The median (IQR) age of the 66 patients (48 boys/men and 18 girls/women) was 7.0 years (5.7-8.8). Twelve patients (18.2%) had a positive OFC result; 6 of 8 (75%) patients with a history of an immediate reaction to CN failed the OFC. Anaphylaxis was experienced by 5 of these 12 (42%) patients. A history of an immediate reaction to CN and the CN sIgE levels were significantly different for patients with a positive or negative OFC result (p < 0.01). Among patients without a previous immediate reaction to CN, the 95% positive predictive value (PPV) for the CN sIgE level for a positive OFC result was 66.1 kUA/L. CONCLUSIONS: A history of an immediate reaction to CN and high CN sIgE were risk factors for a positive OFC result. The number of positive OFC results was relatively low, but there was a high probability of anaphylaxis. We should consider the indication of OFC carefully for patients with a history of immediate reactions to CN and avoid OFC for patients without such a history whose CN sIgE values are >66.1 kUA/L (95% PPV).

Pine nut allergy in Korean children: Clinical characteristics and diagnostic values of specific IgE against pine nuts.

BACKGROUND: Hypersensitivity reactions to pine nuts in children have been occasionally encountered recently, although reports on pine nut allergy cases are rare worldwide. The study aimed to feature clinical and laboratory findings pertaining to pine nut allergy in Korean children. METHODS: Forty-two subjects were enrolled through a retrospective review of medical records, from September 2010 to December 2015, at the Department of Pediatrics in Ajou University Hospital. The demographic profiles, clinical characteristics, and laboratory findings were evaluated. RESULTS: Twenty-four patients showed immediate-type reactions after exposure to pine nuts (the allergic group), while the remaining 18 were atopic controls, who exhibited no allergic symptoms (the tolerant group). The median age of the subjects in the allergic group was three years. More than half of the subjects in this group experienced allergic symptoms within 5min, and seven of them experienced anaphylaxis. The median level of pine nut-specific immunoglobulin E (sIgE) in the allergic group (1.62kUA/L) was significantly higher (p=0.014) than that in the tolerant group (0.11kUA/L), with an optimal cut-off level of 0.40kUA/L (sensitivity, 66.7% and specificity, 77.8%). The positive decision point of pine nut-sIgE (specificity, 100%) to distinguish the allergic and tolerant groups was 2.84kUA/L. However, there was no difference in pine nut-sIgE levels between the anaphylaxis and non-anaphylaxis cases. CONCLUSION: About 30% of children with pine nut allergy experienced anaphylaxis. The optimal cut-off level of pine nut-sIgE to distinguish the allergic and tolerant groups was 0.40kUA/L and the positive decision point was 2.84kUA/L.

Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy.

BACKGROUND: Food Allergy Herbal Formula-2 (FAHF-2) is a 9-herb formula based on traditional Chinese medicine that blocks peanut-induced anaphylaxis in a murine model. In phase I studies FAHF-2 was found to be safe and well tolerated. OBJECTIVE: We sought to evaluate the safety and effectiveness of FAHF-2 as a treatment for food allergy. METHODS: In this double-blind, randomized, placebo-controlled study 68 subjects aged 12 to 45 years with allergies to peanut, tree nut, sesame, fish, and/or shellfish, which were confirmed by baseline double-blind, placebo-controlled oral food challenges (DBPCFCs), received FAHF-2 (n = 46) or placebo (n = 22). After 6 months of therapy, subjects underwent DBPCFCs. For those who demonstrated increases in the eliciting dose, a repeat DBPCFC was performed 3 months after stopping therapy. RESULTS: Treatment was well tolerated, with no serious adverse events. By using intent-to-treat analysis, the placebo group had a higher eliciting dose and cumulative dose (P = .05) at the end-of-treatment DBPCFC. There was no difference in the requirement for epinephrine to treat reactions (P = .55). There were no significant differences in allergen-specific IgE and IgG4 levels, cytokine production by PBMCs, or basophil activation between the active and placebo groups. In vitro immunologic studies performed on subjects' baseline PBMCs incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 levels, and increased numbers of regulatory T cells than untreated cells. Notably, 44% of subjects had poor drug adherence for at least one third of the study period. CONCLUSION: FAHF-2 is a safe herbal medication for subjects with food allergy and shows favorable in vitro immunomodulatory effects; however, efficacy for improving tolerance to food allergens is not demonstrated at the dose and duration used.

Walnut allergy in peanut-allergic patients: significance of sequential epitopes of walnut homologous to linear epitopes of Ara h 1, 2 and 3 in relation to clinical reactivity.

BACKGROUND: Peanut allergy is a frequent and potentially life-threatening food allergy. Despite the large taxonomic distance between the plants, peanut-allergic patients often react to tree nuts such as walnuts. While the allergens of peanut and walnut have a high degree of homology in their amino-acid sequences, it is unknown whether this similarity is responsible for the observed co-reactivity. Therefore, we analyzed the binding of specific IgE antibodies to sequential epitopes of peanut and walnut in peanut-allergic patients with and without walnut allergy. METHODS: The IgE binding to previously described sequential epitopes of peanut and the homologous regions of walnut was assessed in 32 peanut-allergic patients using a peptide microarray technology. Twelve patients had a clinically relevant walnut allergy and 20 were tolerant to walnut. Inhibition assays with peanut peptides and corresponding walnut sequences were performed to show specific binding to sequential epitopes. RESULTS: No differences in the recognition of sequential epitopes could be found between peanut-allergic patients with or without walnut allergy. Only a few patients showed IgE binding to walnut sequences that corresponded to sequential epitopes of peanut. In the inhibition assays, no relevant cross-reacting IgE antibodies could be detected for the peptides analyzed. CONCLUSION: Our results indicate that although they share a rather high degree of homology with the corresponding regions of walnut allergens, the sequence stretches previously identified as sequential IgE binding epitopes of Ara h 1, Ara h 2 and Ara h 3 have no IgE binding equivalents in walnut allergens.

What do asthmatics have to fear from food and additive allergy?

International studies report marked increases in the prevalence of food allergy, along with increases in hospital admissions and emergency presentations for severe allergic reactions due to foods. The prevalence of self-reported food allergy is common, but generally exceeds that which can be verified from challenge studies, although nut allergies appear to be an important exception to this rule. Studies examining food allergy deaths suggest that those who die of food allergy usually have co-existent asthma. Adolescents and young adults are at most risk, and adrenaline auto-injectors are sub-optimally used. Food chemical sensitivity is very commonly reported but not usually verified by challenge testing. However, the exception to this is sulphite sensitivity, which can elicit reproducible reactions in some. The increasing prevalence of severe food allergies and awareness of its risk in those with asthma demands an especially rigorous approach to the diagnosis and management of co-existent food allergy and asthma, especially in young people who appear to be at most risk from death from severe food allergy.

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.

Factors predicting anaphylaxis to peanuts and tree nuts in patients referred to a specialist center.

BACKGROUND: Although acute allergic reactions after ingestion of peanuts and tree nuts are common, fatalities are rare. Other than patients with coexisting asthma, it is currently not possible to predict which patients are most likely to develop severe reactions. OBJECTIVE: The aim of this study was to determine which clinical and laboratory parameters best predict the likelihood of severe allergic reactions. METHODS: From 1992 to 2004, we collected detailed information on the clinical severity and allergy test results of 1094 patients with peanut and tree nut allergy attending a regional allergy center. In a subgroup of 122 patients, sera were assayed for activity of enzymes involved in the catabolism of bradykinin. RESULTS: Severe pharyngeal edema was 3.8 (2.1-6.9) times more common in patients with severe rhinitis and 2.6 (1.8-3.7) more common after ingestion of tree nuts compared with peanuts. Patients with serum angiotensin-converting enzyme concentrations <37.0 mmol/L had a 9.6 (1.6-57)-fold risk of severe pharyngeal edema. Life-threatening bronchospasm was most likely in patients with severe asthma (relative risk, 6.8 [4.1-11.3]) and less so in patients with milder asthma (2.7 [1.7-4.0]). Altered levels of consciousness were more likely in patients with severe eczema (3.1 [1.1-8.4]). CONCLUSION: Severity of coexisting atopic diseases predicted which patients attending a tertiary referral clinic were most likely to develop life-threatening allergic reactions to peanuts and tree nuts. Patients with the lowest serum angiotensin-converting enzyme concentrations were more likely to develop life-threatening pharyngeal edema, suggesting that this complication may be partly mediated by bradykinin.

[A move meat beginning...and evolutive]. / Un début de repas mouvementé...et évolutif.

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.

Anaphylaxis due to Brazil nut skin testing in a walnut-allergic subject.

The diagnosis and management of nut allergy can be difficult because of the possible severity of the clinical manifestations and the cross reactivity between different species. We report a case of anaphylaxis due to skin testing in a young adult with clinically ascertained walnut allergy. After an episode of anaphylaxis due to walnut ingestion, a routine diagnostic workup was carried out, involving skin prick test with commercial extracts, prick by prick with fresh food and CAP-RAST assay for different nuts. Immediately after pricking with fresh Brazil nut, a severe episode of anaphylaxis occurred, that required epinephrine and intravenous steroids. The subject had never eaten Brazil nut before. Therefore we hypothesize a cross reactivity effect, since this phenomenon is well known for tree nuts. Our case suggests that in vivo diagnosis, especially if fresh nuts are used, should be performed only if adequate equipment to treat anaphylaxis is available.

Anaphylaxis--a patient perspective.

In order to help us better understand our patients' experiences, Australian Family Physician is pleased to introduce the first in a series of articles written by people who are willing to share their stories. Ella was requested to write this article by AFP's Editor in Chief. Ella is now a year 11 student at Williamstown High School, Victoria.

Tree nut allergy: risk factors for development, mitigation of reaction risk and current efforts in desensitization.

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.

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.

[Diarrhea as manifestation of allergic diseases. The difficult search for the allergen]. / Diarrhö als Manifestation allergischer Erkrankungen. Die schwierige Suche nach dem Allergen.

Allergy is a very uncommon cause of diarrhoea. Other mechanisms, medical diseases and infections, psychological and pseudoallergic reactions, intolerance reactions, and enzyme defects/deficiency, and many other conditions are much more common. If food allergy is strongly suspected diagnosis may be difficult, even for allergologists, as it requires a mosaic of history, skin and in vitro tests, diagnostic diet, and even provocation tests. It is important to recognise diarrhoea "accompanying" allergic urticaria and anaphylactic reactions as part of the symptomatology of the primary dermatological or allergic disease and to refer the patient to the appropriate specialist.

Fatal food allergy and opportunities for risk minimisation.

IgE-mediated food allergy affects up to 6% of children and 2% of adults. Fatal food allergic reactions are rare. Management of food allergy requires accurate identification of allergen(s), risk assessment, education on allergen avoidance / management of allergic reaction, and follow up. A case of fatal allergic reaction to cashew ingestion is reported, illustrating the importance of these aspects of management.

Specific IgE to common food allergens in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis is a major public health problem, often starting in early childhood and sometimes followed by other allergic diseases. Although hypersensitivity to foods is assumed to play an essential role in the development of atopic dermatitis in some patients, little is known about common food allergens in Iranian children with atopic dermatitis. OBJECTIVES: This study was designed to identify probable food allergens in Iranian children with atopic dermatitis and find the relationship between food sensitization and the severity of atopic dermatitis. METHODS: This study included 90 children aged 2-48 months with atopic dermatitis. Skin prick tests for cow's milk, hen's egg, almond, potato and soybean were done. Serum specific IgE to 20 food allergens was also screened. RESULTS: Among children with atopic dermatitis, the frequency of food sensitization was 40% by skin prick test and 51% by food-specific IgE. Children with atopic dermatitis were most commonly sensitized to cow's milk (31%), hen's egg (17.7%), tree nuts (17.7%), wheat (12.2%), potato (11.1%), tomato (8.8%) and peanut (8.8%). In 42 children with moderate to severe eczema, sensitivity to food allergens was 78.5% by skin prick test and 88% by serum specific IgE evaluation. CONCLUSION: Our results showed that cow's milk, hen's egg and tree nuts were the most common food allergens in Iranian children with atopic dermatitis. Sensitization to foods was much higher in patients with moderate to severe atopic dermatitis. Determining specific IgE in children with atopic dermatitis can be helpful in managing these patients.