Outcomes of oral food challenges in a real-world setting, with predictors of outcomes.

BACKGROUND: Oral food challenge (OFC) remains the reference standard for food allergy (FA) diagnosis. OBJECTIVE: This study reports a single-center observational experience with all OFCs conducted over 3 years. METHODS: All OFCs performed at an outpatient office were tracked. The OFCs were conducted without strict prespecified inclusion or exclusion criteria. Demographic information along with results of diagnostic testing and results of the OFCs were recorded. RESULTS: A total of 1132 OFCs were performed, with a median age of 4 years (interquartile range = 2.0-10.0). Of the 1132 OFCs, 862 (76.1%) tolerated the food, whereas 232 (20.5%) experienced a reaction, and 38 (3.4%) did not complete the OFC because of food refusal. The highest percentage of tolerated food was shellfish (91.1%), with the lowest percentage of tolerated food being baked egg (66.1%). There were 66 (5.8%) OFCs that were deemed to be high risk, of which 35 (53.0%) tolerated the food. More than 50% of reactions occurred on the first or second dose, with the most common clinical symptom being urticaria or angioedema, with 29.2% of reactions treated with epinephrine. There were several factors that predicted tolerating an OFC, including the food challenge, the reason for food avoidance, older age at the time of OFC and less reactive skin prick testing, and lower food-specific immunoglobulin E levels. CONCLUSION: Certain factors can predict tolerating an OFC, and even those considered to be high risk can be safely completed in an outpatient setting, with most tolerating the food, and most reactions not requiring treatment with epinephrine.

Anaphylaxis knowledge gaps and future research priorities: A consensus report.

BACKGROUND: Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively. OBJECTIVE: We sought to systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact and feasibility. METHODS: We convened a 25-member multidisciplinary panel of anaphylaxis experts. Panelists formulated knowledge gaps/research priority statements in an anonymous electronic survey. Four anaphylaxis themed writing groups were formed to refine statements: (1) Population Science, (2) Basic and Translational Sciences, (3) Emergency Department Care/Acute Management, and (4) Long-Term Management Strategies and Prevention. Revised statements were incorporated into an anonymous electronic survey, and panelists were asked to rate the impact and feasibility of addressing statements on a continuous 0 to 100 scale. RESULTS: The panel generated 98 statements across the 4 anaphylaxis themes: Population Science (29), Basic and Translational Sciences (27), Emergency Department Care/Acute Management (24), and Long-Term Management Strategies and Prevention (18). Median scores for impact and feasibility ranged from 50.0 to 95.0 and from 40.0 to 90.0, respectively. Key statements based on median rating for impact/feasibility included the need to refine anaphylaxis diagnostic criteria, identify reliable diagnostic, predictive, and prognostic anaphylaxis bioassays, develop clinical prediction models to standardize postanaphylaxis observation periods and hospitalization criteria, and determine immunotherapy best practices. CONCLUSIONS: We identified and systematically appraised anaphylaxis knowledge gaps and future research priorities. This study reinforces the need to harmonize scientific pursuits to optimize the outcomes of patients with and at risk of anaphylaxis.

Severity grading system for acute allergic reactions: A multidisciplinary Delphi study.

BACKGROUND: There is no widely adopted severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions, thus limiting the ability to optimize and standardize management practices and advance research. OBJECTIVE: The aim of this study was to develop a severity grading system for acute allergic reactions for use in clinical care and research. METHODS: From May to September 2020, we convened a 21-member multidisciplinary panel of allergy and emergency care experts; 9 members formed a writing group to critically appraise and assess the strengths and limitations of prior severity grading systems and develop the structure and content for an optimal severity grading system. The entire study panel then revised the grading system and sought consensus by utilizing Delphi methodology. RESULTS: The writing group recommended that an optimal grading system encompass the severity of acute allergic reactions on a continuum from mild allergic reactions to anaphylactic shock. Additionally, the severity grading system must be able to discriminate between clinically important differences in reaction severity to be relevant in research while also being intuitive and straightforward to apply in clinical care. Consensus was reached for all elements of the proposed severity grading system. CONCLUSION: We developed a consensus severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions. Successful international validation, refinement, dissemination, and application of the grading system will improve communication among providers and patients about the severity of allergic reactions and will help advance future research.

Differences in oral food challenge reaction severity based on increasing age in a pediatric population.

BACKGROUND: Food allergy reactions range from mild to severe with differences in age appearing to be an important factor associated with reaction severity. OBJECTIVE: To define differences in oral food challenge (OFC) reaction severity in pediatric patients from infancy to adolescence using objective clinical outcomes and standardized reaction grading tools. METHODS: Retrospective review of all positive OFC results at 2 large institutions between September 2016 and February 2019. Reaction severity was defined by presence of cardiovascular, neurologic, lower respiratory, or laryngeal symptoms, epinephrine requirement, and grading using 2 established food allergy reaction scales. RESULTS: Infants and toddlers had fewer reactions involving cardiovascular, neurologic, lower respiratory, or laryngeal symptoms compared with older age groups. Epinephrine was also required less frequently during reactions in infants and toddlers, compared with older age groups. There was no difference in reaction severity in infants and toddlers based on clinical history of eczema. Increasing age was significantly correlated with increased epinephrine requirement (R2 = 0.12, P = .002), elevated Consortium of Food Allergy Research score (R2 = .012, P = .003), and approached significance for increased Practical Allergy score (R2 = .005, P = .05). History of asthma and sesame allergy were identified to be positively correlated with more severe reactions. CONCLUSION: Infants and young toddlers have less severe reactions during OFCs compared with older age groups supporting early food introduction practices. In children under 12 months of age, severe reactions are most rare calling into question screening practices using specific allergy testing before food introduction. Standardized reaction grading tools may be valuable instruments to categorize reaction severity during OFCs.

Food reactions during avoidance: Focus on peanut.

OBJECTIVE: Peanut allergy has historically been difficult to manage, with most cases persisting into adulthood. Novel therapies for peanut allergy treatment are on the horizon, yet allergists must maintain a robust understanding of the risks and benefits of the current standard of therapy, avoidance diet. DATA SOURCES: A comprehensive literature search using PubMed of reviews and clinical articles was performed. STUDY SELECTIONS: Articles discussing peanut or other food-related allergic reactions, accidental exposures or anaphylaxis pertinent to avoidance diet or comparative to oral immunotherapy trials were selected. RESULTS: Peanut remains a leading allergen associated with accidental ingestions responsible for food-related reactions, both mild and severe. Fatal reactions, however, are rare and measures such as anaphylaxis plans can significantly decrease the risk of accidental anaphylaxis. Patients may over estimate situations thought to increase risk for reactions to peanut, such as inhalation or contact through skin. In oral immunotherapy trials, the rate of anaphylaxis secondary to treatment was significantly higher than avoidance practices. CONCLUSION: Clinicians should continue to discuss avoidance as a viable option for long-term peanut allergy management and empower patients to differentiate relevant situations in which accidental reactions might occur.

Comparison of comorbid diagnoses in children with and without eosinophilic esophagitis in a large population.

BACKGROUND: Previous reports suggest a higher prevalence of comorbid diseases in patients with eosinophilic esophagitis (EoE), although few have systematically quantified comorbidities in pediatric patients. OBJECTIVE: To define the rate of comorbid diagnoses in pediatric EoE patients compared with rates in those without EoE. METHODS: Retrospective cross-sectional review of electronic medical records for patients seen in a single large pediatric primary care network between January 2007 and December 2016 (n = 456,148). International Classification of Diseases, Ninth and Tenth Revision codes were used to determine prevalence rates for coexisting diagnoses. RESULTS: A total of 428 patients held a diagnosis for EoE. Significant differences in rate of comorbid diseases included allergic rhinoconjunctivitis (60.0% of EoE cohort vs 17.4% of non-EoE cohort, P < .0001); asthma (59.8% of EoE, 21.4% of non-EoE, P < .0001); atopic dermatitis (17.8% of EoE, 6.6% of non-EoE, P < .0001); adrenal insufficiency (2.6% of EoE, 0.4% of non-EoE, P < .0001); autism spectrum disorder (7.5% of EoE, 1.9% of non-EoE, P < .0001); celiac disease (5.6% of EoE, 0.9% of non-EoE, P < .0001); connective tissue diseases (1.4% of EoE, 0.1% of non-EoE, P < .0001); cystic fibrosis (0.9% of EoE, 0.05% of non-EoE, P < .0001); inflammatory bowel disease (0.7% of EoE, 0.2% of non-EoE, P = .03); type 1 diabetes mellitus (1.2% of EoE, 0.3% of non-EoE, P = .0069). CONCLUSION: Children with EoE have markedly higher rates of both atopic and non-atopic diseases compared with children without EoE. These associations have important implications for comprehensive EoE care and future research regarding associated disease mechanisms.

Differences in egg and milk food challenge outcomes based on tolerance to the baked form.

BACKGROUND: Previous studies suggest inclusion of baked egg and milk in the diet of children with egg or cow's milk (CM) allergy might positively affect native tolerance. However, differences in native food reactivity based on historical baked tolerance are not fully understood. OBJECTIVE: To assess differences in native egg and CM oral food challenge (OFC) outcomes based on presenting history of tolerance and exposure to these foods in the baked form. METHODS: This study is a retrospective review of all egg and CM OFCs at the Children's Hospital of Philadelphia (Philadelphia, Pennsylvania) over 4 years (N = 580). History of baked ingestion was compared with OFC pass rate, eliciting dose, epinephrine use, reaction classification, and recent skin test reaction or specific immunoglobulin E level. RESULTS: There were 115 egg- and 70 CM-positive challenge reactions, with most eliciting anaphylaxis. Children tolerating baked egg passed OFC more frequently (75%) compared with children who avoided baked egg (58%; P = .01) or never ingested egg (45%; P < .0001). For positive reactions, children tolerant of baked egg reacted at higher eliciting doses of native egg (median 3.0 g, range 0.125-15.75 g) compared with those avoiding baked egg (median 0.69 g, range 0.13-10.0 g; P = .03) and those with no egg exposure (median 0.88 g, range 0.13-13.88 g; P = .01). Further, epinephrine use was lower in children tolerating baked egg (10%) compared with children avoiding baked egg (22%; P = .02) and compared with children who never ingested egg (32%; P = .0001). These differences were not observed for CM challenges. CONCLUSION: Children who historically tolerated baked egg were less sensitive to native egg during OFC compared with children whose baked reactivity was largely unknown.

Factors Associated With Noncompliance With Long-term Follow-up Care Among Pediatric Cancer Survivors.

Most childhood cancer survivors do not receive risk-based care through a survivorship program, but factors associated with dropping out of care are unclear. This study aimed to identify characteristics of pediatric cancer survivors who do not return to a cancer center survivorship program for recommended care after at least 1 visit compared with those who continue to attend. Patient characteristics (demographics, school functioning, psychiatric history) and treatment characteristics (diagnosis, treatment) were abstracted from medical records for all eligible patients. Unadjusted and multivariable logistic regression analyses examined the associations among patient and treatment characteristics and nonattendance. The charts of 400 eligible patients (children below 18, n=123; adults, n=277) were reviewed. Of these, 60.3% of patients had not been seen in clinic within 1 year of their last recommended follow-up appointment. Adult-aged survivors were less likely to return to clinic than child-aged survivors (P<0.001). For child survivors, longer time off treatment was associated with noncompliance with follow-up. For adult survivors, current age, nonwhite race, and longer time off treatment were associated with noncompliance. Additional methods to identify survivors at risk for noncompliance with follow-up and interventions for at-risk survivors are needed to improve survivorship care.

Graded Administration of Second Dose of Moderna and Pfizer-BioNTech COVID-19 mRNA Vaccines in Patients With Hypersensitivity to First Dose.

Two mRNA coronavirus disease 2019 (COVID-19) vaccines, Moderna and Pfizer-BioNTech, require 2 doses for maximum efficacy. This case series reports the safety and immunogenicity of a graded administration of the second dose of the Moderna and Pfizer-BioNTech COVID-19 vaccines in patients with immediate hypersensitivity reactions to the first dose.

Allergic Comorbidity in Eosinophilic Esophagitis: Mechanistic Relevance and Clinical Implications.

Allergic eosinophilic esophagitis (EoE) is a chronic, allergen-mediated inflammatory disease of the esophagus, and the most common cause of prolonged dysphagia in children and young adults in the developed world. While initially undistinguished from gastroesophageal reflux disease-associated esophageal eosinophilia, EoE is now recognized as a clinically distinct entity that shares fundamental inflammatory features of other allergic conditions and is similarly increasing in incidence and prevalence. The clinical and epidemiologic associations between EoE and other allergic manifestations are well established. In addition to exaggerated rates of atopic dermatitis, IgE-mediated food allergy, asthma, and allergic rhinitis in EoE patients, each of these allergic manifestations imparts individual and cumulative risk for subsequent EoE diagnosis. As such, EoE may be a member of the "allergic march"-the natural history of allergic manifestations during childhood. Several determinants likely contribute to the relationship between these conditions, including shared genetic, environmental, and immunologic factors. Herein, we present a comprehensive review of allergic comorbidity in EoE. We discuss areas of the genome associated with both EoE and other allergic diseases, including the well-studied variants encoding thymic stromal lymphopoietin and calpain 14, among other "atopic" regions. We summarize ways that environmental factors (such as microbiome-altering pressures and aeroallergen exposure) may predispose to multiple allergic conditions including EoE. Finally, we touch on some fundamental features of type 2 inflammation, and the resulting implications for the development of multiple allergic manifestations. We conclude with an analysis of the "type 2" biologics, and how mechanistic similarities between EoE and the other allergic manifestations have important implications for screening and treatment of the allergic patient.

Eosinophilic esophagitis during sublingual and oral allergen immunotherapy.

PURPOSE OF REVIEW: The aim of this review is to discuss the current evidence regarding the development of eosinophilic esophagitis (EoE) in individuals undergoing oral and sublingual immunotherapy (SLIT) for both food and environmental allergens. Cumulative incidence of EoE in patients on allergen immunotherapy for peanut, milk, and egg is estimated. RECENT FINDINGS: De novo development of EoE in patients undergoing oral and SLIT has been demonstrated on the scale of case reports and prospective randomized trials. However, few individuals with EoE-like symptoms during immunotherapy undergo endoscopy, and the long-term outcomes of immunotherapy-associated EoE are unknown. SUMMARY: Evidence exists to suggest that allergen immunotherapy could place individuals at risk for the development of EoE, the true incidence of which may vary depending on antigen exposure and methods used to define the condition.