Food Matrix Composition Affects the Allergenicity of Baked Egg Products.

BACKGROUND: Egg allergy is common and caused by sensitization to ovomucoid and/or ovalbumin. Many egg-allergic patients are able to tolerate eggs baked into other foods, such as muffins. Although heating egg extensively reduces allergens, the effect of other food ingredients on allergenicity of eggs, or the "matrix effect," is less well studied. OBJECTIVE: We aimed to define how food matrices impact the matrix effect in egg allergenicity. METHODS: Enzyme-linked immunosorbent assay was used to quantify ovalbumin and ovomucoid in extracts from various baked egg products: plain baked egg without a matrix, and muffins baked using either wheat flour, rice flour, or a wheat flour/banana puree mix. Allergen-specific immunoglobulin E (IgE)-blocking enzyme-linked immunosorbent assays were performed using the egg product extracts on egg-allergic patient sera to determine whether the amount of extracted egg protein in each extract correlated with how well the extracts could bind patients' egg IgE. RESULTS: Baking eggs in any muffin matrix led to an increase in the amount of extractable ovalbumin and a decrease in the amount of extractable ovomucoid compared with plain baked egg. Compared with wheat muffins, rice muffins had more extractable ovalbumin and wheat/banana muffins had more extractable ovalbumin and ovomucoid. The egg allergens in the extracts were able to block egg-allergic patients' egg IgE. CONCLUSIONS: Food matrices affect egg allergen availability. Patients and families should be advised that substitutions in baked egg muffin recipes can affect the amount of egg allergens in foods and potentially affect the risk of food allergic reaction.

When leuprolide acetate is essential to care: A review of the literature and framework for assessing drug allergy.

Gonadotropin-releasing hormone agonists are uncommonly associated with hypersensitivity reactions. To date, there have been few reports of these cases by allergists and no clear published protocols on testing. Here, we report the case of a patient who had a potential reaction to leuprolide acetate depot and a framework for assessing for drug hypersensitivity with the available literature in mind.

Development of an innovative curriculum for paediatricians on peanut allergy prevention: How do we address current guidelines?

BACKGROUND: There exists strong evidence for the early introduction of peanut to at-risk infants for the primary prevention of peanut allergy. There is a need for educational initiatives to assist in dissemination and implementation of updated clinical guidelines on peanut allergy prevention. APPROACH: The aim for this project was to create an innovative curriculum for paediatricians on peanut allergy prevention. The Intervention to Reduce Early Allergy (Peanut) in Childhood (iREACH) study was leveraged to recruit paediatricians for a needs assessment. Materials from the iREACH study, including an educational YouTube video and knowledge survey, were evaluated. Applying findings from the needs assessment, an innovative curriculum was developed, and updated knowledge survey questions were developed. EVALUATION: The iREACH YouTube video had suboptimal viewing behaviours, and iREACH participants had high baseline knowledge scores that did improve after viewing the video. The majority of respondents to the needs assessment felt that all paediatricians needed access to an effective educational module on peanut allergy prevention, and they wanted a broadly accessible curriculum that incorporated quality media and content segmentation. An online, interactive curriculum was developed that includes clinical cases and games, and updated knowledge questions were created with associated internal structure and reliability evidence, as well as relation to other variables evidence. IMPLICATION: The next steps of this project will focus on curriculum implementation and evaluation through a randomised, prospective study with the aim to serve as an educational model for how to integrate specialty-specific guidelines into broader clinical practice through education.

Variation in the Guidelines for the Acute Management of Anaphylaxis in Pediatric Patients: An International Narrative Review.

OBJECTIVES: Evidence-based guidelines have been created and disseminated by multiple organizations to standardize the care of pediatric patients with anaphylaxis. Differences across these guidelines can cause confusion and potentially errors in clinical practice leading to patient harm. The aim of this study was to describe and identify patterns of variation in the current guidelines. METHODS: A narrative review with 3 major components was designed. First, a narrative review of current, peer-reviewed, guidelines published by national and international allergy and immunology, pediatric, and emergency medicine organizations was performed. That was followed by a gray literature review of guidelines by resuscitation councils and national health organizations. The third component focused on the translation of these guidelines at local and institutional levels by reviewing clinical pathways published by academic institutions. RESULTS: With regard to the fixed epinephrine autoinjector dosing, 50% (6 of 12) of the reviewed guidelines offered weight-based and 41.7% (5 of 12) age-based dosing recommendations. Furthermore, different weight cutoffs for the 0.15- and 0.3-mg autoinjectors were identified among guidelines. Variation was identified in the description of intramuscular epinephrine concentration ("1:1000," "1 mg/mL," or both), the recommended concentration for intravenous administration ("1:10,000" or "1:1000"), or the rate of infusion or titration. Eight of the 12 guidelines (66.7%) recommend a dose in milligrams, and 33.3% (4 of 12) in micrograms. Five of 12 (41.7%) used both milliliters and milligrams or micrograms. CONCLUSIONS: Notable variation in the current guidelines for the acute management of anaphylaxis in the pediatric population was identified. Flagging this variability could help inform a consensus-based approach toward harmonization of guidelines, which in turn could streamline the management of anaphylaxis in pediatric patients across the United States, Canada, Ireland, the United Kingdom, Europe, Australia, and New Zealand, and hopefully prevent errors and mitigate patient harm.

Validated anxiety assessments among pediatric patients with peanut allergy on oral immunotherapy.

BACKGROUND: Although efficacy, safety, and quality of life measures associated with peanut oral immunotherapy (OIT) have been studied, the relationship between peanut OIT and clinical anxiety has not yet been evaluated. The latter is important to help providers and families have an improved shared medical decision discussion around the benefits of initiating OIT. OBJECTIVE: To investigate the relationship between undergoing OIT and anxiety in patients with peanut allergy. METHODS: In this prospective cross-sectional cohort study, using validated and age-appropriate anxiety scales administered with electronic survey questionnaires, we used generalized linear regressions to compare anxiety between patients undergoing OIT and similar patients with peanut allergy but not on OIT (controls). RESULTS: In the younger cohort (<7 years, n = 80), there was generally a low prevalence of diagnosable anxiety across patients on OIT and controls. In the older cohort (>7 years, n = 125), there was a higher prevalence of anxiety but no clinically meaningful difference between anxiety scores of patients on OIT and controls. In the older cohort, patients with asthma were more likely to have higher mean anxiety scores (P = .04), as were female patients compared with male patients (P = .004). A subanalysis of separation anxiety scores in the older cohort revealed that younger age (7-12 years vs >12 years, P < .001), non-White race (P = .04), and eczema (P = .02) were found to be meaningful predictors of higher scores. A subanalysis of social anxiety on the older cohort pointed toward non-White race as a meaningful predictor of higher scores (P < .02). CONCLUSION: The clinical implications of these findings suggest that allergists should particularly consider screening children with food allergy for anxiety and anxiety subtypes among patients who are non-White, female, or have asthma.

Food Allergy Management Practices Utilizing Individual Patient Thresholds: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

The paradigm for food allergy management has been strict avoidance of the food allergen. There is literature supporting a "high-threshold" phenotype, those who tolerate a small-to-modest amount of allergen but react to larger amounts. There is no consensus for best practice for these "high-threshold" individuals. We sought to understand management practices of "high-threshold" reactors using a survey that was distributed to a random sample of fellows and members of the American Academy of Allergy, Asthma, and Immunology. There were 89 respondents from the United States and Canada (11% response rate), with 64 (72%) answering all questions. Participants worked in private (52%) and academic practice (38%) and saw a median of 30 food allergic patients monthly. Eighty-one percent of respondents reported management strategies other than strict avoidance. When threshold was known, strategies ranged from allowing ingestion up to a specified amount (57%), proactively advising ingestion to a certain amount (56%), or oral immunotherapy (47%). Participants were more likely to choose a permissive approach for a mild reaction in a high-threshold milk-allergic patient compared with a peanut-allergic patient (83% vs 71%, p=.01). Important factors that influenced the approach included severity of reaction (52%), comfort with family/patient using emergency medications (42%), and family/patient preferences (41%). These survey results suggest that food allergy management recommendations are no longer binary in nature, with clinicians solely recommending avoidance for those who are allergic and ingestion for those who may not be.

Recent Update in Food Protein-Induced Enterocolitis Syndrome: Pathophysiology, Diagnosis, and Management.

Food protein-induced enterocolitis syndrome (FPIES), though first reported in the 1970s, remains poorly understood and likely underdiagnosed. It is a non-immunoglobulin E (IgE)-mediated food allergy syndrome, most commonly identified in infancy and childhood. It can manifest as a constellation of symptoms following food ingestion, including repetitive and projectile emesis (1-4 hours), accompanied by pallor, lethargy, muscular hypotonia, and diarrhea (5-10 hours). In more severe reactions, significant leukocytosis with neutrophilia, thrombocytosis, metabolic derangements, methemoglobinemia, anemia, low albumin, and total protein may be present. Hypotension and ultimately hypovolemic distributive shock may occur in up to 15%-20% of cases. The diagnosis of FPIES is challenging and providers continue to face difficulties in management. This review article aims to highlight the most recent updates in epidemiology, natural history, pathophysiology, potential diagnostic markers, and guidelines for the management of FPIES.

A practical focus on wheat oral immunotherapy.

Wheat is a dietary staple in many cultures as well as a common food allergen. Although not as extensively studied as other forms of oral immunotherapy, the current literature suggests that wheat oral immunotherapy (WOIT) can result in successful desensitization. There has only been one multicenter, double-blind, randomized controlled trial of WOIT, along with several open-label nonrandomized trials. The trials were limited by several factors, including small sample sizes; demographic skew; and heterogeneity in dosing, duration, and outcomes. The majority of WOIT regimens results in desensitization, with literature that indicates that a longer duration and higher dosing may lead to more clinical success. WOIT has been associated with adverse events, including allergic reactions, but these events seem to decrease over time. Study on WOIT is underway, but evidence from trials suggests it can be successful and safe. Further studies will need to optimize dosing protocols to improve efficacy and safety.

A review of the safety of oral immunotherapy in clinical trial and real-world studies.

Safety concerns are a barrier to oral immunotherapy (OIT). This review aims to describe OIT safety events and explore potential risk factors and mitigating factors. Published clinical and real-world OIT studies were reviewed for data on safety outcomes in OIT. Gastrointestinal symptoms are one of the most common adverse reactions associated with OIT, and persistent symptoms can be associated with an eosinophilic response. Allergic reactions are increased in OIT compared with avoidance; however, these symptoms tend not to be severe and to decrease over time. Despite OIT, epinephrine usage persists in studies and life-threatening reactions (though rare) have occurred. High baseline food specific immunoglobulin E levels, aggressive dosing, uncontrolled atopic comorbidities, and poor adherence to protocols may contribute to the severity of adverse events. OIT remains a shared decision that incorporates best medical evidence and appropriate patient selection. It requires individualized care and action plans to ensure safe outcomes.

Wheat oral immunotherapy.

PURPOSE OF REVIEW: The prevalence of food allergy is increasing on a global scale, and therefore increased attention is being paid to specific food allergy epidemiology and management. There has been a large amount of progress made in the last decade on human trials of wheat oral immunotherapy (WOIT). RECENT FINDINGS: To date, there has been one multicenter, double-blind, randomized controlled trial of WOIT, one randomized, noncontrolled trial of WOIT, and several smaller, nonrandomized clinical trials of WOIT. WOIT trials are generally limited by smaller sample sizes, affecting the demographic skew of evaluated patients. In addition, there is minimal standardization of efficacy and safety outcomes between trial protocols, making head-to-head comparison challenging. However, some common themes emerge. The majority of WOIT regimens result in successful desensitization, and success is more likely with higher maintenance dosing for longer periods of time. Limited studies have looked at sustained unresponsiveness in WOIT. WOIT can induce allergic reactions, including anaphylaxis, but more severe reactions often have an associated augmenting factor, such as exercise. Lower maintenance doses likely are associated with less severe reactions, and food modification and/or adjunct therapeutics may also decrease the risk of reactions. SUMMARY: WOIT trials are ongoing and will optimize updosing protocols and maintenance doses to improve efficacy and safety.

The impact of food matrices on egg allergenicity.

Background: Although many studies show the impact of high and prolonged heating on allergenicity, scarce research exists that examined the impact of the food matrix effect. We presented a case that demonstrates the need for further investigation into this field. Case: An 8-month-old breast-fed girl with a history of moderate eczema presented with concern for food allergy. At 7 months old, she seemed to have difficulty with nursing after consumption of peanut butter, and her pediatrician recommended further avoidance. On presentation to allergy, she had not yet consumed eggs; therefore, skin testing was obtained for both peanut and egg. Her skin testing result to peanut was negative, whereas to egg was elevated at 5/20 mm. To further support clinical decision-making, blood work was obtained, and the egg white specific immunoglobulin E (IgE) value was elevated to 1.33 kU/L. It was recommended to the family to pursue home introduction of peanut and return for oral challenge to baked egg. At 14 months old, the patient returned for oral challenge and successfully tolerated one-half of a muffin. She was discharged with instructions to continue consumption of one-half of a muffin ideally three or more times a week, which the parents reported she continued to tolerate. Conclusion: When the patient was 24 months old, the mother decided, without consultation, to introduce banana-chocolate chip muffins. With the first two ingestions, she developed immediate urticaria. On the third consumption, she developed anaphylaxis, which required epinephrine, with rapid improvement. The patient subsequently returned to regular consumption of standard egg muffins (as well as bananas and chocolate individually), which she continued to tolerate. Based on our patient's ability to tolerate baked egg muffins without banana but significant reaction to baked egg muffins with banana, a potential explanation is that the addition of banana disrupted the egg-wheat matrix. This report points toward a continued need to investigate the role food matrices play on the allergenicity of foods. Furthermore, this case demonstrated the importance of adhering to allergist-prescribed recipes to prevent allergic reactions.

Idiopathic T cell lymphopenia identified in New York State Newborn Screening.

Quantification of T-cell receptor excision circles (TRECs) for newborn screening for SCID has advanced the diagnosis of severe combined immune deficiency (SCID). However, it has led to the identification of infants with T cell lymphopenia without known cause. The clinical characteristics, appropriate laboratory monitoring, and outcomes of patients remain unclear. We performed a retrospective review of clinical and laboratory studies for 26 infants collected from 7 New York State referral centers from 2010 to 2016 with low TRECs (mean, 70copies/µl) and subnormal CD3 counts (mean, 1150/cubicmm). Over time absolute CD3 counts increased in 17 and decreased in 9; 22 (85%) have done well clinically regardless of absolute T cell values. Additional infants with TCL will continue to be identified in newborn screening panels. While most patients seem to do well clinically, parameters for diagnosis and monitoring have yet to be formalized, and additional information needs to be collected, causes and outcomes reported.