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BACKGROUND: The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH)-formerly AR101-has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy-related quality of life. METHODS: We present a subset analysis of PALISADE-ARC004 participants (aged 4-17 years) who received 300 mg PTAH daily for a total of ~1.5 (Group A, n = 110) or ~2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double-blind, placebo-controlled food challenge (DBPCFC); skin prick testing; peanut-specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores. RESULTS: Continued maintenance with PTAH increased participants ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose-limiting symptoms. Immune biomarkers showed a pattern consistent with treatment-induced desensitization. Among PTAH-continuing participants, the overall and treatment-related exposure-adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life. CONCLUSIONS: These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response.

For doses up to 24 mg peanut protein, a mix of peanut and oat flour is used (4.6% peanut protein). The peanut baseline challenge starts with 0.3 mg peanut protein and continues stepwise up to 250 mg peanut protein (Table 1). Keywords: food allergy; peanut allergy; oral immunotherapy; treatment EN food allergy peanut allergy oral immunotherapy treatment 594 597 4 05/10/23 20230501 NES 230501 Key messages This is a study protocol for a trial of low-dose, slow up-dosing peanut oral immunotherapy. [Extracted from the article]

Background: There is substantial interest in immunotherapy and biologicals in IgE‐mediated food allergy. Methods: We searched six databases for randomized controlled trials about immunotherapy alone or with biologicals (to April 2021) or biological monotherapy (to September 2021) in food allergy confirmed by oral food challenge. We pooled the data using random‐effects meta‐analysis. Results: We included 36 trials about immunotherapy with 2126 mainly child participants. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5.–21.4, high certainty); cow's milk (RR 5.7, 1.9–16.7, moderate certainty) and hen's egg allergy (RR 8.9, 4.4–18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300 mg or 1000 mg peanut protein was 2. Oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0–1.2, low certainty) or severe reactions in peanut allergy (RR 1,6, 0.7–3.5, low certainty), but may increase (mild) adverse reactions in cow's milk (RR 3.9, 2.1–7.5, low certainty) and hen's egg allergy (RR 7.0, 2.4–19.8, moderate certainty). Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8–3.8, moderate certainty). Results were unclear for other allergies and administration routes. There were too few trials of biologicals alone (3) or with immunotherapy (1) to draw conclusions. Conclusions: Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow's milk and hen's egg allergy. More research is needed about quality of life, cost and biologicals. [ABSTRACT FROM AUTHOR]

Adverse reactions after food intake are commonly reported and a cause of concern and anxiety that can lead to a very strict diet. The severity of the reaction can vary depending on the type of food and mechanism, and it is not always easy to disentangle different hypersensitivity diagnoses, which sometimes can exist simultaneously. After a carefully taken medical history, hypersensitivity to food can often be ruled out or suspected. The most common type of allergic reaction is immunoglobulin E (IgE)–mediated food allergy (prevalence 5–10%). Symptoms vary from mild itching, stomach pain, and rash to severe anaphylaxis. The definition of IgE‐mediated food allergy is allergic symptoms combined with specific IgE‐antibodies, and therefore only IgE‐antibodies to suspected allergens should be analyzed. Nowadays, methods of molecular allergology can help with the diagnostic process. The most common allergens are milk and egg in infants, peanut and tree nuts in children, and fish and shellfish in adults. In young children, milk/egg allergy has a good chance to remit, making it important to follow up and reintroduce the food when possible. Other diseases triggered by food are non‐IgE‐mediated food allergy, for example, eosinophilic esophagitis, celiac disease, food protein‐induced enterocolitis syndrome, and hypersensitivity to milk and biogenic amines. Some of the food hypersensitivities dominate in childhood, others are more common in adults. Interesting studies are ongoing regarding the possibilities of treating food hypersensitivity, such as through oral immunotherapy. The purpose of this review was to provide an overview of the most common types of food hypersensitivity reactions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Peanut allergy (PA), a common food allergy, is increasing in prevalence and is associated with high rates of anaphylaxis. Prevalence of food‐related anaphylaxis is higher in children and adolescents than in adults, and the pediatric incidence is increasing. We conducted a systematic literature review and meta‐analysis to determine the incidence of peanut‐induced anaphylaxis in children and/or adolescents with PA. Methods: Literature searches were conducted using the PubMed database and through supplemental methods. Eligible articles for inclusion were peer‐reviewed studies published in English that reported the incidence of anaphylaxis in pediatric PA using the 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network criteria, sample size, and follow‐up duration. Incidence rates were calculated as person‐years at risk or a crude incidence rate was calculated. Meta‐analyses of pooled data were conducted using the I2 statistic as the measure of heterogeneity. Results: A total of 830 citations were screened; 8 met the study inclusion criteria and were selected for review. Pooled meta‐analysis estimates of the incidence of (1) anaphylaxis among children/adolescents with food allergies, (2) anaphylaxis among children/adolescents with PA, and (3) accidental exposure to peanuts among children/adolescents with PA were 3.72 cases per 100 person‐years (95% confidence interval [CI] = 2.35, 5.10), 2.74 cases per 100 person‐years (95% CI = 1.42, 4.05), and 12.28 cases per 100 person‐years (95% CI = 11.51, 13.05), respectively. Conclusions: The risks of anaphylaxis among children with food allergies and those with PA contribute to the serious overall burden of PA and food allergy for children and their families. [ABSTRACT FROM AUTHOR]

Alpha‐gal syndrome should be suspected also in children in case of typical allergic symptoms in the evening or night during tick seasons and the event of recall urticaria. It is, however, still a challenge for both patients and clinicians. [ABSTRACT FROM AUTHOR]

Background: Allergic reactions to food allergens usually occur after ingestion. However, fear of reactions to airborne peanut is a common concern for people with peanut allergy. There are no scientific reports on severe reactions with airborne peanut allergen. Objective: To investigate the occurrence of allergic reactions in peanut‐allergic children undergoing airborne peanut challenge and to determine levels of airborne peanut protein in a separate experimental evaluation. Methods: Eighty‐four children with peanut allergy underwent an airborne peanut challenge, 0.5 m from a bowl of peanuts for 30 min under controlled conditions. In a separate experiment, airborne peanut proteins from roasted and dry‐roasted peanuts were collected at varying distances and at varying times with an electret SensAbues filter connected to an air pump. Collected airborne peanut proteins were extracted, dissolved and detected by ELISA. Basophil activation test was used to confirm biological activity. Results: No moderate/severe allergic reactions to airborne peanut allergens were observed. Two children (2%) had mild rhino‐conjunctivitis which required no treatment. The IgE‐antibodies to peanut or Ara h 2 did not predict a reaction. In the experimental set‐up, biological active peanut proteins were detected, in a very low amount, in median 166 ng/ml for dry‐roasted and 33 ng/ml for roasted peanuts and decreased dramatically when the collection occurred at a greater distance (0.5–2 m) from the peanut source. Increased exposure time did affect the amount of collected peanut protein at 0 m, and the highest median was obtained after 60 min (p =.012); for time trend p =.0006. Conclusions and Clinical Relevance: Allergic reactions to airborne peanut proteins are rare and cannot be predicted by high levels of IgE‐antibodies to peanut or Ara h 2. Only small amounts of biologically active peanut proteins were detected in the air and seem unlikely to trigger moderate/severe allergic reactions. [ABSTRACT FROM AUTHOR]

Background: Hazelnut‐specific IgE antibodies (sIgEs) in serum support the diagnosis of hazelnut allergy, but extract‐based tests have low diagnostic specificity, commonly leading to over‐diagnosis. Measuring sensitization to individual allergen components may enhance the diagnosis of hazelnut allergy. We systematically examined data on diagnostic accuracy of sIgE to commercially available hazelnut components to compare their individual contributions in diagnosing hazelnut allergy. Methods: Seven databases were searched for diagnostic studies on patients suspected of having hazelnut allergy. Studies employing component‐specific IgE testing on patients whose final diagnosis was determined by oral food challenges were included in the meta‐analysis. Study quality was assessed as recommended by Cochrane. Results: Seven cross‐sectional studies and one case‐control study were identified, seven presenting data on children (N = 635), and one on a mixed age population. Overall, the diagnostic accuracies of sIgE to both Cor a 9 and Cor a 14 were significantly higher than for Cor a 1‐sIgE (P <.05). In children, the specificity of Cor a 14‐sIgE at 0.35 kUA/L cutoff was 81.7% (95% CI 77.1, 85.6), and 67.3% (60.3, 73.6) for Cor a 9‐sIgE. The specificities for Cor a 1‐sIgE and hazelnut‐sIgE were 22.5% (7.4, 51.2) and 10.8% (3.4, 29.8), respectively. The sensitivity of Cor a 1‐sIgE (60.2% [46.9, 72.2]) was lower than for hazelnut extract‐sIgE (95.7% [88.7, 98.5]), while their specificities did not differ significantly. Conclusion: sIgE to Cor a 14 and Cor a 9 hazelnut storage proteins increases diagnostic specificity in assessing hazelnut allergy in children. The combined use of hazelnut extract and hazelnut storage proteins may improve diagnostic value. [ABSTRACT FROM AUTHOR]

Background: Peanut oral immunotherapy (pOIT) has showed good short‐term outcomes, but allergic reactions may prevent effective up‐dosing and is a major cause of stopping OIT. In placebo‐controlled trials, omalizumab has been shown to facilitate allergen immunotherapy and increase tolerance to peanut. Objective: We hypothesized that by combining omalizumab with pOIT, and monitor treatment effects with basophil allergen threshold sensitivity tests (CD‐sens), peanut allergic patients could safely initiate pOIT and thereafter slowly withdraw omalizumab. Methods: This is the 2nd part of a one‐armed open phase‐2 study where peanut allergic adolescents (n = 23) started pOIT after an individualized omalizumab treatment. The pOIT dose was increased from 280 to 2800 mg peanut protein in 8 weeks followed by an individualized step‐wise withdrawal of omalizumab, based on clinical symptoms and CD‐sens levels. pOIT continued for 12 weeks followed by an open peanut challenge. Peanut CD‐sens and allergen‐binding activity (ABA) and IgE‐ab, IgG‐ab and IgG4‐ab to peanut and its components were measured during the study. Results: All 23 patients successfully reached the 2800 mg maintenance dose. Moderate/systemic allergic reactions were rare while receiving full‐dose omalizumab. Eleven of 23 (48%) successfully continued with pOIT after omalizumab was stopped. Compared to treatment failures, median baseline IgE‐ab to peanut components Ara h 1‐3 and CD‐sens to peanut were significantly lower among successfully treated patients and IgG4‐ab to peanut, Ara h 2 and 6 increased significantly more during treatment. Conclusions and clinical relevance: This study indicates that omalizumab is an effective adjunctive therapy for initiation and rapid up‐dosing of pOIT; however, adverse events from pOIT become more frequent as omalizumab doses are decreased. Clinical trials registration: ClinicalTrials.gov; NCT02402231. EudraCT; 2012‐005625‐78. [ABSTRACT FROM AUTHOR]

Background: Specific immunoglobulin E (IgE) sensitization to wheat is more common than a doctor's confirmed wheat allergy and is also frequently observed in grass pollen-allergic patients (pollinosis patients). Thus, the objective of this study was to investigate the level and feature of serological IgE cross-reactivity between grass pollen and wheat in a cohort of pollinosis subjects with no diagnosis of wheat allergy. Methods: Seventy-two children, aged 5–17 years, with a doctor's diagnosis of pollinosis, IgE towards grass pollen, and currently eating wheat were recruited. Serum samples were analyzed for IgE against wheat, timothy grass/wheat-specific allergen components, Pru p 3, and cross-reactive carbohydrate determinants (CCD) and specific IgE-binding inhibition experiments were performed. Results: Sixty percent of the grass pollen subjects were sensitized to wheat with a median of 0.5 kUA/L. Wheat-sensitized subjects were more often sensitized to the two allergens, Phl p 12 and CCD, known to be cross-reactive between grass and wheat. Sensitizations to seven wheat-specific allergens derived from the gluten fraction were, with the exception of one individual, only found in wheat-sensitized subjects. These subjects also more often reported current and past history of allergy to staple foods (milk, egg, wheat, soy, and fish). Conclusion: Wheat sensitization caused by cross-reactivity but also by sensitization to wheat-specific allergens was common in the grass-allergic children and also associated with allergy to staple foods other than wheat. The results indicate the presence of a subgroup of pollinosis patients with simultaneous sensitization to wheat and food allergy not only caused by cross-reactions. [ABSTRACT FROM AUTHOR]

Correct management and classification of anaphylaxis is mandatory. Records of emergency department (ED) visits to any of the three pediatric hospitals in Stockholm, because of reactions to foods during 2007, were identified. A retrospective analysis of clinical ED records of 371 children with 381 unique occasions of reactions to foods was performed. Symptoms/signs of reactions to foods recorded for classification of anaphylaxis were related to those presented in the EAACI Taskforce position paper on Anaphylaxis in Children (Allergy 2007; 62: 857). Forty-six different symptoms/signs of reactions to foods were retrieved. Several severe signs or symptoms from the respiratory tract and signs indicating reduced brain perfusion were not described in detail in the EAACI paper, hampering correct classification of anaphylaxis including grading of severity in our material. After modification of the EAACI classification including such signs and symptoms, we were able to classify 128 (35%) children with anaphylaxis. Seventy children (19%) did not fulfill our modified EAACI's criteria for anaphylaxis. They had been given adrenaline before or at arrival to hospital, possibly preventing anaphylaxis. Another 173 (47%) children/ adolescents had neither been given adrenalin, nor fulfilled the criteria for anaphylaxis. Classification of food-induced anaphylaxis and severity grading should be built on signs and symptoms to facilitate diagnosis. The existing EAACI tool is helpful, but for Swedish children it is not quite applicable, in particular because of the lack of description of some respiratory, neurological or possible cardiovascular signs and symptoms. [ABSTRACT FROM AUTHOR]

The article explores the impact of one year of oral immunotherapy on the gut microbiota and plasma metabolome of peanut-allergic young children. The study found that oral immunotherapy increased gut microbiota richness and Clostridia abundance, while plasma acylcarnitines and fatty acids showed different trajectories in treated and untreated children. The research suggests that these changes may be linked to peanut desensitization and expands our understanding of the mechanisms underlying peanut oral immunotherapy in young children. [Extracted from the article]

Background: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.Methods: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.Results: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older.Conclusions: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .). [ABSTRACT FROM AUTHOR]

Availability of "exotic" foods is steadily increasing. In this report, we describe the first case of anaphylaxis to crocodile meat. The patient was a 13-year-old boy with severe immunoglobulin E-mediated allergy to chicken meat. When tasting crocodile meat for the first time, he developed an anaphylactic reaction. Cross-reactivity between chicken and crocodile meat was suspected to have triggered this reaction. Basophil activation and immunoglobulin E testing confirmed the boy's allergic reaction to crocodile meat proteins. Molecular analysis identified a crocodile α-parvalbumin, with extensive sequence homology to chicken α-parvalbumin, as the main cross-reactive allergen. We conclude that crocodile meat can be a potent food allergen and patients with allergy to chicken meat should be advised to avoid intake of meat from crocodile species. Both foods and people travel around the world and accessibility to exotic foods is steadily growing. As a result, novel allergic cross-reactivities are likely to become a challenge in the management of food allergy and, as our report illustrates, cross-reactivity has to be considered even between foods that might not intuitively be perceived as related. [ABSTRACT FROM AUTHOR]