Clinical utility analysis of the Hoxb8 mast cell activation test for the diagnosis of peanut allergy.

BACKGROUND: Peanut allergy is among the most severe and common food allergies. The diagnosis has a significant impact on the quality of life for patients and their families. An effective management approach depends on accurate, safe, and easily implementable diagnostic methods. We previously developed a cell-based assay using Hoxb8 mast cells (Hoxb8 MCs) aimed at improving clinical allergy diagnosis. In this study, we assessed its diagnostic performance by measuring blinded sera from a prospectively enrolled and pre-validated peanut allergy cohort. METHODS: Hoxb8 MCs were passively sensitized with sera from peanut-allergic and peanut tolerant children and adolescents (n = 112). Degranulation of Hoxb8 MCs was quantified upon stimulation with dose-titrated peanut extract by means of flow cytometry, using CD107a as activation marker. The results from the Hoxb8 mast cell activation test (Hoxb8 MAT) were compared to established diagnostic assays such as the skin prick test (SPT), specific IgE (sIgE) levels, and the basophil activation test (BAT). Additionally, serum samples from BAT nonresponders were assessed with the Hoxb8 MAT. RESULTS: Hoxb8 MAT displayed a robust dose-dependent activation to peanut extract, with a cutoff value of ≤5.2% CD107a positive cells. The diagnostic accuracy was highest at allergen concentrations ≥100 ng/mL, with an area under the receiver operating characteristic curve (AUROC) of 0.97, 93% sensitivity, and 96% specificity, outperforming traditional SPT and sIgE tests. When compared to BAT, Hoxb8 MAT exhibited comparable diagnostic efficacy. Moreover, sera from BAT nonresponders were accurately classified into allergics and nonallergics by the Hoxb8 MAT. CONCLUSIONS: The Hoxb8 MAT demonstrated a very good diagnostic precision in patients prospectively assessed for peanut allergy comparable to the fresh whole blood-based BAT. Additionally, it demonstrated its value for accurate classification of BAT nonresponders into allergic and nonallergic individuals. Further investigations into its utility in the routine clinical setting are warranted.

Safety of Oral Food Challenge for Individuals with Low Egg White and Ovomucoid-Specific IgE Antibodies.

INTRODUCTION: During an oral food challenge (OFC), there is a risk of adverse reactions, including anaphylaxis. Therefore, the physician should carefully conduct the OFC. This study aimed to evaluate the OFC results in individuals with low levels of egg white (EW)- and ovomucoid (OVM)-specific immunoglobulin E (sIgE) and the safety of a hen's egg (HE) OFC in these individuals. METHODS: A total of 2,058 individuals with low EW- or OVM-sIgE underwent HE-OFC at two institutions in Kumamoto prefecture, located in the western area of Japan, between January 1, 2017, and December 31, 2021, within 1 year of recorded sIgE measurements. The ImmunoCAP systems were used to measure sIgEs. The HE-OFC test was performed according to the 2017 Food Allergy Guidelines in an open and unblinded method. RESULTS: Five hundred and one individuals (24.3%) had low EW-sIgE levels (class 2 or lower), and 926 (45.0%) had low OVM-sIgE levels (class 2 or lower). Individuals with low EW-sIgE had lower total IgE and OVM-sIgE than did those with high EW-sIgE (greater than class 2). Those with low OVM-sIgE had lower total IgE and EW-sIgE than did those with high OVM-sIgE (greater than class 2). Among the individuals with low EW-sIgE, 86.4% (433/501 cases) passed the OFC without symptoms. Among the individuals with low OVF-sIgE, 82.6% (765/926 cases) passed the OFC without symptoms. CONCLUSION: More than 80% of individuals with suspected IgE-dependent HE allergy and low levels of EW- or OVM-specific IgE were able to consume at least a small amount of HE. As the OFC results are independent of the loading dose in cases with low EW- or OVM-sIgE, a medium-dose HE-OFC may be performed safely in individuals with no history of anaphylaxis.

Clinical Features of Quail Egg Ingestion in Patients with Acquired Tolerance to Hen Eggs: A Case Series Study.

INTRODUCTION: Patients with hen's egg allergy are often instructed to avoid consuming other avian eggs, such as quail eggs. However, it is unclear whether patients with an acquired tolerance to hen eggs continue to avoid consuming quail eggs. This study aimed to evaluate the clinical features of quail egg ingestion. METHODS: This prospective case series included children aged ≥1 year with hen's egg allergy who were recruited between October 2019 and February 2021 in our hospital. We conducted an oral food challenge (OFC) with three boiled quail eggs to evaluate the clinical features of quail egg ingestion in patients with acquired tolerance to hen eggs. The primary outcome was a positive OFC after ingesting three quail eggs. Secondary outcomes were cross-antigenicity between hen and quail eggs observed through the skin prick test (SPT) and pattern of quail egg allergy, comprising the onset of reaction, and severity. The correlation between the diameters of the wheals with SPT in hen and quail eggs was evaluated using the Pearson product-moment correlation coefficient. RESULTS: A total of 62 patients underwent the quail egg OFC. The median (interquartile range) age of the participants was 3 (2-5) years. Thirty-three (53%) patients had a history of anaphylaxis due to hen eggs. The median total immunoglobulin E (IgE) level in patients who underwent the OFC with half a heated whole hen's egg was 271 (98-593) IU/mL. The median specific IgE level in egg white and ovomucoid was 9.7 (3.2-21.5) and 4.4 (1.3-6.9) UA/mL, respectively. The quail egg OFC results revealed that none of the 59 patients who ate the three quail eggs completely had an allergic reaction. The SPT-positive and SPT-negative rates in raw and boiled hen and quail egg whites were both correlated. The diameters of wheals with SPT in raw hen and quail egg whites and yolks were positively correlated. CONCLUSION: Patients with an acquired tolerance to hen eggs may not be required to avoid consuming quail eggs.

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.

Peanut oral immunotherapy using an extensively heated and baked novel composition of peanuts.

BACKGROUND: Oral immunotherapy (OIT) is an increasingly acceptable therapeutic option for peanut-allergic (PA) children, despite significant side effects. Major peanut allergenic proteins are heat-resistant and are not rendered hypoallergenic after baking or cooking. Lyophilized peanut protein-MH (LPP-MH) is a novel composition from developing peanuts, enabling cooking-induced reduction in allergenicity. We aimed to explore the safety and efficacy of OIT, with extensively heated and baked (EHEB) LPP-MH in PA children. METHODS: In a single-arm, single-center, pilot study, PA children with a single highest tolerated dose of <100 mg peanut protein were placed on a 40-week OIT protocol with 300 mg daily of heat-treated LPP-MH. A repeat open peanut food challenge was performed after 40 weeks of treatment and at a 6-12 months of follow-up visit. RESULTS: Thirty-three children with PA were enrolled, with a mean cumulative tolerated dose (MCTD) of 71.2 mg PP (95% CI 45-100 mg). After 40 weeks, 32/33 patients were able to consume more than 300 mg of natural PP, with MCTD of 1709 mg (CI 365-3675 mg). There were no severe allergic reactions requiring epinephrine, during any of the observed LPP-MH challenges or any treatment related doses at home. After 6-12 months on daily maintenance, the MCTD was 8821 mg (95% CI 1930-13,500 mg). This enabled most children age-appropriate dietary inclusion of peanuts. CONCLUSION: An OIT protocol with heat-treated LPP-MH, a novel composition from developing peanuts, seems a potentially safe and efficacious OIT modality for PA children, enabling the introduction of dietary levels of peanut proteins in highly allergic PA children. Validation in randomized controlled studies is mandated.

A nomogram for predicting food allergy in infants with feeding problems and malnutrition.

BACKGROUND AND OBJECTIVE: As oral food challenge (OFC) cannot be performed routinely in the general outpatient, this study aimed to construct a nomogram to predict the odds of food allergy in infants with idiopathic feeding problems and malnutrition. METHODS: From August 2018 to December 2021, 289 infants (median age, 6 months; P25-P75, 4-8) with idiopathic feeding problems and malnutrition were enrolled from seven hospitals in Shanghai, China. Food allergy was defined as a positive response to a skin prick test or OFC, with gastrointestinal, dermatologic, or respiratory symptom improvement after 4 weeks of avoidance of the suspected food. Demographic characteristics, Cow's Milk-related Symptom Scores (CoMiSS), and blood eosinophil amounts were evaluated for their associations with food allergy. Multivariable logistic regression analysis was used to identify variables to develop a nomogram model with the bootstrapped-concordance index as an assessment metric. RESULTS: Totally 249 of 289 infants had food allergy (86.2%). After logistic regression analysis, the feeding pattern (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 2.13-13.09), a family history of allergy (OR = 1.79, 95% CI: 0.71-4.51), CoMiSS (OR = 1.45, 95% CI: 1.19-1.77), and eosinophil percentage (OR = 1.33, 95% CI: 1.11-1.60) were used to develop the model, which had a good performance with an area under the curve of 0.868 (95% CI: 0.792-0.944) and a bootstrapped-concordance index of 0.868. CONCLUSION: Food allergy is common in infants with idiopathic feeding problems and malnutrition. The developed nomogram may help identify infants with food allergy for further diagnosis.

Is Component-Specific Antibody Testing Sufficient to Replace the Oral Food Challenge in the Diagnostics of Peanut-Sensitized Children? A Proof-of-Concept Study.

(1) Peanut allergy is associated with high risk of anaphylaxis which could be prevented by oral immunotherapy. Patients eligible for immunotherapy are selected on the basis of a food challenge, although currently the assessment of antibodies against main peanut molecules (Ara h 1, 2, 3 and 6) is thought to be another option. (2) The current study assessed the relationship between the mentioned antibodies, challenge outcomes, skin tests and some other parameters in peanut-sensitized children. It involved 74 children, divided into two groups, based on their response to a food challenge. (3) Both groups differed in results of skin tests, levels of component-specific antibodies and peanut exposure history. The antibody levels were then used to calculate thresholds for prediction of challenge results or symptom severity. While the antibody-based challenge prediction revealed statistical significance, it failed in cases of severe symptoms. Furthermore, no significant correlation was observed between antibody levels, symptom-eliciting doses and the risk of severe anaphylaxis. Although in some patients it could result from interference with IgG4, the latter would not be a universal explanation of this phenomenon. (4) Despite some limitations, antibody-based screening may be an alternative to the food challenge, although its clinical relevance still requires further studies.

Efficacy of very-low-dose oral food challenge in children with severe hen egg allergy: A retrospective, single-center case series.

BACKGROUND: To avoid complete elimination of hen eggs (HE) from diet, we introduced a very-low-dose (VLD) oral food challenge (OFC) in patients with severe HE allergy in 2019. Herein, we investigated the efficacy of VLD HE OFC for achieving the full dose OFC. METHODS: Patients with an overt allergic reaction to LD (1/32 HE [≤100 mg]) or less, egg white (EW) protein within 6 months were included. In the VLD group, patients not achieving full-dose OFC (1/2 HE: 1600 mg EW protein) within 2 years were excluded. We retrospectively compared the rate of passing a full-dose OFC between patients who underwent a LD OFC before 2019 (LD group) and those who underwent a VLD OFC (1/100 HE: 32 mg EW protein) after 2019 (VLD group). The period for passing the full-dose OFC was evaluated using Kaplan-Meier survival analysis. RESULTS: We enrolled 411 and 111 patients in the LD and VLD groups, respectively. The median age at OFC initiation was 2.2 [1.5-3.6] and 2.1 [1.4-3.2] years in the LD and VLD groups, respectively. EW- and ovomucoid-specific IgE levels were 38.3 (12.5-72.9) and 21.0 (8.3-46.2) kUA/L in the LD group and 49.8 [18.8-83.9] and 32.1 [15.6-67.8] kUA/L in the VLD group, respectively. Over 4 years, the LD and VLD groups passed the full-dose OFC at rates of 70 and 95%, respectively, with significant differences (log-rank test, P < 0.001). CONCLUSIONS: VLD HE OFC may contribute to passing a full-dose OFC in patients with severe HE allergies.

High-dimensional immune profiles correlate with phenotypes of peanut allergy during food-allergic reactions.

BACKGROUND: Food challenges carry a burden of safety, effort and resources. Clinical reactivity and presentation, such as thresholds and symptoms, are considered challenging to predict ex vivo. AIMS: To identify changes of peripheral immune signatures during oral food challenges (OFC) that correlate with the clinical outcome in patients with peanut allergy (PA). METHODS: Children with a positive (OFC+ , n = 16) or a negative (OFC- , n = 10) OFC-outcome were included (controls, n = 7). Single-cell mass cytometry/unsupervised analysis allowed unbiased immunophenotyping during OFC. RESULTS: Peripheral immune profiles correlated with OFC outcome. OFC+ -profiles revealed mainly decreased Th2 cells, memory Treg and activated NK cells, which had an increased homing marker expression signifying immune cell migration into effector tissues along with symptom onset. OFC- -profiles had also signs of ongoing inflammation, but with a signature of a controlled response, lacking homing marker expression and featuring a concomitant increase of Th2-shifted CD4+ T cells and Treg cells. Low versus high threshold reactivity-groups had differential frequencies of intermediate monocytes and myeloid dendritic cells at baseline. Low threshold was associated with increased CD8+ T cells and reduced memory cells (central memory [CM] CD4+ [Th2] T cells, CM CD8+ T cells, Treg). Immune signatures also discriminated patients with preferential skin versus gastrointestinal symptoms, whereby skin signs correlated with increased expression of CCR4, a molecule enabling skin trafficking, on various immune cell types. CONCLUSION: We showed that peripheral immune signatures reflected dynamics of clinical outcome during OFC with peanut. Those immune alterations hold promise as a basis for predictive OFC biomarker discovery to monitor disease outcome and therapy of PA.

The role of basophil activation test and component-resolved diagnostics in the workup of egg allergy in children at low risk for severe allergic reactions: A real-life study.

BACKGROUND: The gold standard for diagnosing egg allergy in children is the oral food challenge (OFC). However, OFCs are time-consuming and risky procedures. Our study aimed to evaluate the utility of the basophil activation test (BAT) and component-resolved diagnostic in the diagnostic workup of children with egg allergy. METHODS: Overall, 86 children aged 6 months to 17 years, suspected of egg allergy, underwent OFC with boiled egg according to international standardized protocols. BAT and specific immunoglobulin E (sIgE) testing to component egg proteins (Gal d 1-4) were also performed. RESULTS: Of the 22 children who reacted to boiled egg, only one experienced anaphylaxis during the challenge. BAT was performed in samples obtained by 75 of the 86 patients of our cohort. Egg white and yolk protein extracts induced CD63 upregulation in the egg-allergic (EA) children compared with sensitized children that tolerated boiled egg (we registered an overall mean of CD63 expression in the EA population of 44.4% [SD 34.1] for egg white and 34.7% [SD 31.3] for egg yolk vs. 12.5% [SD 19.1] and 10.0% [SD 16.0] in sensitized children). BAT could discriminate between true egg allergy and egg sensitization in our population. As a second-line diagnostic step, the positivity of BAT for egg white or Gal d 1-sIgE resulted in a 40.9% OFC reduction, especially for those with a positive outcome. CONCLUSION: The BAT may be implemented in the diagnostic workup of egg allergy in children and, in a stepwise approach, separately or combined with Gal d 1-sIgE, may predict the allergic status and reduce the number of positive OFCs in children with egg allergy at low risk for severe reactions.

Relationship between serum allergen-specific immunoglobulin E and threshold dose in an oral food challenge.

BACKGROUND: Several studies have reported threshold doses for food allergens. However, evidence regarding potential risk factors for low threshold doses is limited. Moreover, the relationship between threshold dose and specific immunoglobulin E (sIgE) levels to causative foods remains unclear. This study examined the relationship and the risk factors for a low threshold dose. METHODS: We recruited children with food allergies and examined the risk factors for a positive oral food challenge (OFC) with a low threshold dose and anaphylaxis. RESULTS: We evaluated 2501 children with food allergies (1667 [67%] boys; median age, 4.9 years) to eggs (n = 1096), milk (n = 671), wheat (n = 370), peanuts (n = 258), walnuts (n = 65), and cashews (n = 41). Of these patients, 234 (9%) reacted to ≤30 mg protein of causative foods and 620 (25%) reacted to ≤100 mg protein of causative foods. The sIgE level to causative foods was a significant independent factor for positive OFCs with a threshold dose of ≤30 mg for milk, wheat, and peanuts; ≤ 100 mg for eggs, milk, wheat, peanuts, and cashews; and anaphylaxis from eggs, milk, wheat, peanuts, and walnuts. High sIgE levels to causative foods were associated with a lower threshold dose of the OFC and anaphylaxis during the OFC. CONCLUSIONS: Approximately 9% of patients reacted to ≤30 mg protein of causative foods. The potential risks of anaphylaxis should be considered during OFCs for patients with elevated sIgE levels.

Sesame allergy in children: New insights into diagnosis and management.

Sesame is a potentially potent allergen that can trigger skin, gastrointestinal, and respiratory tract symptoms, and anaphylaxis. Only 20% to 30% of sesame-allergic children develop tolerance. The prevalence of sesame allergy depends on local diets and ranges from 0.1% to 0.9%. A high risk of accidental exposure to sesame has resulted in mandatory food labeling in many countries. More than half of patients with sesame allergy are also allergic to peanut/tree nuts. Serum-specific IgE testing with a quantitative Ses i 1 component can be performed safely and has higher clinical specificity and better positive predictive value for oral food challenge (OFC) than whole sesame extract or skin prick testing (SPT). Compared with SPT or OFC, in vitro Ses i 1 testing requires no special techniques and carries no risk of reactions. Diagnosis of suspected sesame allergy begins with a thorough history and physical examination. A positive sesame extract test (≥0.1 kUA /L) should prompt further testing. In patients with a high probability of reacting, results of component testing may facilitate a decision about performing an OFC. In a Japanese study of OFC and Ses i 1, there was a 5% probability of a positive OFC with Ses i 1 sIgE levels <0.13 kUA /L, and a 50% probability of a positive OFC with levels >32.0 kUA /L. Most patients could safely consume sesame if sIgE levels were <0.13 kUA /L. Ses i 1 testing can be used to guide appropriate management (avoidance, emergency medication, and oral immunotherapy).

Oral food challenge outcomes in children and adolescents in a tertiary centre: A 5-year experience.

AIM: Oral food challenges (OFC) are an important tool in the assessment of food allergy. We sought to identify factors available at initial assessment visit which were associated with successful outcome or challenge failure in Australian children. METHODS: We conducted a retrospective review of all paediatric patients who underwent OFC in our allergy service over a 5-year period. Clinical data comprising patient demographics, co-morbidities, skin prick test (SPT) results, nature of previous reactions, elapsed time since previous reactions and outcome at OFC were recorded. RESULTS: Four hundred and fifty-six OFCs were conducted, with 56 cases (12.3%) resulting in a reaction. Likelihood of reaction at OFC was significantly increased for patients with atopic dermatitis (odds ratio 1.99). When stratified by food substance, atopic dermatitis had the strongest association with reaction within the peanut group (odds ratio 3.2), and no association was demonstrated for soy or prawn. Increasing SPT wheal size (P < 0.001) and previous history of anaphylaxis to the challenge food (P < 0.001) correlated with failure at OFC. A low-risk group was identified, of patients with no clear history of prior reaction to the challenge food, and SPT result <3 mm. CONCLUSIONS: Factors identified at assessment visit which correlated with reaction at OFC are atopic dermatitis, prior history of anaphylaxis, and increasing SPT wheal size. Domiciliary OFC could be considered in a select low-risk group of patients undergoing food challenge. This study was performed at a single centre with limited sample size, further large-scale and multicentre study verification of our data will provide more accurate representation of the Australian demographic.

Does the severity of atopic dermatitis change with allergic sensitization? Is it real or a myth?

OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease that can occur at any age. This study aimed to evaluate the impact of food allergy on disease severity as well as clinical/laboratory findings in children with AD. METHODS: Clinical and laboratory data of AD patients evaluated for food allergy between January 2021 and December 2022 were examined retrospectively. RESULTS: Of the 52 patients evaluated, 32 (61.5%) were males, with a median age of 6 months (2-118 months). Among them, 26 (50%) had food allergies (FA) and five (9.6%) had inhalant allergen sensitivity. No significant difference in AD severity was observed between patients with and without FA. However, the FA group showed higher serum lactate dehydrogenase (LDH) levels (343.3 ± 81.5 U/L vs 297.7 ± 77.4 U/L; P = 0.011) and lower red cell distribution width (RDW). Inhalant allergen sensitivity was associated with higher AD severity. CONCLUSION: While guidelines recommend investigating food allergies in moderate to severe AD, this study found no significant difference in the relationship between AD severity and the presence of FA. However, inhalant allergen sensitivity was linked to increased AD severity. Therefore, a comprehensive patient history should include an evaluation of food allergies in children with AD, regardless of disease severity. Elimination and provocation tests related to suspected food items should be performed, and allergenic foods should be removed from the diet if they are found to contribute to the allergy.

Oral food challenge in children with contact urticaria in reaction to cow's milk.

OBJECTIVE: To evaluate the relationship between the occurrence of contact urticaria in reaction to cow's milk in infants and the diagnosis of cow's milk allergy (CMA) established by supervised oral food challenge. METHODS: In this cross-sectional study, we identified 184 children who had undergone 221 oral food challenge (OFC) at a CMA reference center between July 2015 and August 2019. Of these, 23 (12.5%) had a history of contact urticaria to cow's milk and underwent a total of 30 OFC. Baked cow's milk OFC were excluded, and 21 children were included in the study. All data from clinical history and allergy tests (serum-specific IgE dosages and skin prick test [SPT] with reconstituted cow's milk formula) were recorded on standardized forms. The challenge was conducted with reconstituted cow's milk formula in increasing volumes every 15-20 min. RESULTS: 24 OFC were performed; 13/24 (54.2%) for diagnostic purpose and 11/24 (45.8%) to evaluate cow's milk tolerance. Allergy tests were positive in 14 patients (87.5%). Positive oral challenge outcomes were identified in 7/24. One patient had a late flare of atopic dermatitis and five children presented with immediate urticaria (two generalized urticaria and three perioral urticaria). The median papule diameter was 6.5 mm in patients with a positive OFC and 3.75 mm in the negative group (P = 0.02). CONCLUSION: The occurrence of contact urticaria might be the only manifestation among infants sensitized to cow's milk with tolerance to oral ingestion. Reactions due to oral challenge were related to a larger wheal diameter on the SPT.

Food protein-induced enterocolitis syndrome due to buckwheat: A case report.

Buckwheat is a rare causative food for food protein-induced enterocolitis syndrome (FPIES). To date, it is unknown what laboratory data patients with FPIES caused by buckwheat show. We report a 4-year-old female with FPIES caused by buckwheat and the laboratory results. Skin prick, specific IgE antibody, and basophil activation tests were negative; however, the lymphocyte stimulation test (LST) revealed a 10.2-fold increase in activation compared with the negative control. In an open-label oral food challenge (OFC) of 80 g boiled buckwheat noodles, 3 hours after ingestion, vomiting occurred four times in a 2-hour duration. Therefore, we diagnosed the patient with FPIES caused by buckwheat. Her neutrophil count, C-reactive protein, and thymus and activation-regulated chemokine were elevated after the OFC. Moreover, the patient had a positive reaction to the LST, which may theoretically be useful in diagnosing non-immunoglobulin E-mediated gastrointestinal food allergies. FPIES caused by buckwheat is rare; however, we found that the same laboratory results were observed in a comparison of FPIES cases caused by other foods.

IgE-mediated Anisakis allergy in children.

Anisakids are nematodes responsible for different clinical patterns in humans. The well-known human-infecting Anisakis species include members of the Anisakis simplex (AS) complex. Humans usually contract anisakiasis through ingestion of raw or undercooked seafood containing Anisakis larvae. Once Anisakis has been ingested, patients may develop disease driven directly by Anisakis larvae and/or by allergic reaction due to this nematode. The capability of inducing allergic reactions depends on the expression of specific antigens by nematodes and host factors. This study aims to resume actual knowledge about AS and Anisakiasis with regard to epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment. Particular attention is paid to Anisakis allergens and their cross-reactivity on available diagnostic methods, and defining a diagnostic pathway for Anisakis allergy. Because only a few data are available in the literature about pediatric population, we focus on this group of patients specifically.

Updating the CoFAR Grading Scale for Systemic Allergic Reactions in Food Allergy.

BACKGROUND: Immunotherapy is promising as an efficacious treatment for food allergy. Other food allergy treatments are also under development. However, adverse allergic events during treatment, as well as during oral food challenges, are common and reporting is not standardized. OBJECTIVE: A more nuanced grading scale is needed to create a comprehensive and universal system to categorize adverse events and their severity for food allergy clinical trials. METHODS: Starting with the 2012 Consortium for Food Allergy Research (CoFAR) Grading Scale and the World Allergy Organization Grading System, we developed the CoFAR Grading Scale for Systemic Allergic Reactions, Version 3.0, in collaboration with industry partners with expert opinion. RESULTS: The revised CoFAR Grading Scale for Systemic Allergic Reactions has 5 levels of increasing severity, ranging from generalized urticaria, localized angioedema, rhinitis, and abdominal pain (grade 1) to death (grade 5). Systemic reactions are further categorized within each grade by relevant organ system. Mild, single-system reactions are differentiated from mild, multisystem reactions. Lower respiratory tract symptoms are graded on the basis of response to therapy; those that are refractory to standard treatment (eg, requiring >3 doses of intramuscular epinephrine, continuous intravenous epinephrine infusion, and continuous albuterol nebulization) and respiratory compromise requiring mechanical ventilation are classified as grade 4, life-threatening reactions. CONCLUSIONS: Universal and consistent use of the revised CoFAR Grading Scale beyond the CoFAR centers would allow for better data aggregation and safety comparisons in clinical trials for food allergy.

[AN ADOLESCENT CASE OF HAE-NL-C1INH (WHO WAS) MISDIAGNOSED WITH WHEAT ALLERGY AND MULTIPLE DRUG ALLERGIES].

Hereditary angioedema (HAE) is frequently misdiagnosed as drug allergy. It is essential to differentiate HAE from allergy. Diagnosing HAE-normal-C1INH (conventional HAE type III), presenting normal C1-INH, is even more difficult. Here, we report a case of a 17-year-old female diagnosed with HAE and having labeled wheat and multiple drug allergies. She had been suffering from skin edema and abdominal symptoms since childhood. After taking wheat at 13 years old, she had multiple episodes of the same symptoms. Wheat allergy was suspected, and she started eliminating wheat. Multiple attacks were observed after several drug use, and drug allergy was labeled. However, her attacks did not improve after eliminating wheat and the suspected drugs. Her C4 and C1-INH activity was normal, but we diagnosed her with HAE-normal-C1INH based on her family history, multiple attacks after dental procedures, ineffective antihistamines, and significant efficacy of C1-INH infusion. A double-blind, placebo-controlled wheat challenge test at our hospital was negative, and wheat removal was lifted. Drugs could be de-labeled by allergic tests and history. Repeated attacks of unexplained edema and abdominal pain should be differentiated from HAE and lead to an appropriate diagnosis.

Evaluation of the Clinical Characteristics of Patients with Food Protein-Induced Enterocolitis Syndrome: A Multicenter Study.

INTRODUCTION: Food protein-induced enterocolitis syndrome (FPIES) is a rare non-IgE, cell-mediated food allergy disorder. We aimed to report the demographic characteristics, clinical features, and management of pediatric patients with FPIES. METHODS: This retrospective study included all children diagnosed with FPIES at the pediatric allergy departments of the participating twelve study centers from January 2015 to November 2020. RESULTS: A total of 73 patients (39 males, 53.4%) with a male/female ratio of 1.1 were included in the study. The median (interquartile ranges) age at symptom onset was 6 months (0.5-168, 4-9.5). The most frequent offending foods were cow's milk, egg's yolk, fish, and egg's white, identified in 38.4% (n = 28), 32.9% (n = 24), 21.9% (n = 16) and 20.5% (n = 15) of the patients, respectively. The total number of reported FPIES episodes was 290 (3.9 episodes per child). Oral food challenge (OFC) was performed in 54.8% (n = 40) of the patients, and tolerance was detected in 17 OFCs (42.5%) at a median age of 15 months (range 8-132 months). CONCLUSION: FPIES is a non-IgE-mediated food hypersensitivity that commonly affects infants and is often misdiagnosed. The pathophysiology of the disease remains unclear and the low awareness of FPIES among physicians and parents highlights the need for more education.