Dietary exposures and allergy prevention in high-risk infants.

Infants at high risk for developing a food allergy have either an atopic condition (such as eczema) themselves or an immediate family member with such a condition. Breastfeeding should be promoted and supported regardless of issues pertaining to food allergy prevention, but for infants whose mothers cannot or choose not to breastfeed, using a specific formula (i.e., hydrolyzed formula) is not recommended to prevent food allergies. When cow's milk protein formula has been introduced in an infant's diet, make sure that regular ingestion (as little as 10 mL daily) is maintained to prevent loss of tolerance. For high-risk infants, there is compelling evidence that introducing allergenic foods early-at around 6 months, but not before 4 months of age-can prevent common food allergies, and allergies to peanut and egg in particular. Once an allergenic food has been introduced, regular ingestion (e.g., a few times a week) is important to maintain tolerance. Common allergenic foods can be introduced without pausing for days between new foods, and the risk for a severe reaction at first exposure in infancy is extremely low. Pre-emptive in-office screening before introducing allergenic foods is not recommended. No recommendations can be made at this time about the role of maternal dietary modification during pregnancy or lactation, or about supplementing with vitamin D, omega 3, or pre- or probiotics as means to prevent food allergy.

A Novel Germline Heterozygous BCL11B Variant Causing Severe Atopic Disease and Immune Dysregulation.

B-cell lymphoma/leukemia 11B (BCL11B) is a C2H2 zinc finger transcription factor that is critically important for regulating the development and function of a variety of systems including the central nervous system, the skin, and the immune system. Germline heterozygous variants are associated with a spectrum of clinical disorders, including severe combined immunodeficiency as well as neurological, craniofacial, and dermal defects. Of these individuals, ~50% present with severe allergic disease. Here, we report the detailed clinical and laboratory workup of one of the most severe BCL11B-dependent atopic cases to date. Leveraging a zebrafish model, we were able to confirm a strong T-cell defect in the patient. Based on these data, we classify germline BCL11B-dependent atopic disease as a novel primary atopic disorder.

Evolving Interpretation of Screening and Diagnostic Tests in Allergy.

Diagnostic tests for allergy usually are performed to confirm a diagnosis of an allergic disease. If a food allergy suspected, a test can help to determine whether it is present, to monitor its activity over time, and to determine whether the allergy is resolving. In this way, tests are used for diagnosis, monitoring, screening, and prognosis. There are 2 schools of thought for using tests: Frequentist and Bayesian approaches. The Frequentist approach defines probability in terms of the frequency of an event if it were to be repeated numerous times and uses parameters such as sensitivity, specificity, and predictive values to make a diagnosis. In contrast, the Bayesian approach defines probability as the degree of belief or disbelief regarding the diagnosis and asserts that only data are real and that test parameters are to be inferred from the data. There are strengths and limitations to each approach; however, the Bayesian approach provides an algorithm leading to a disease probability. To use the Bayesian approach, test results need to be expressed as a likelihood ratio. This helps to determine how much the result of a test changes the probability of a particular diagnosis. Once a probability of disease is determined, decision thresholds need to be defined so that a treatment decision can be made. Using this Bayesian approach, the concept of a false-positive or false-negative test result becomes obsolete.

The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

Exome sequencing enables diagnosis of X-linked hypohidrotic ectodermal dysplasia in patient with eosinophilic esophagitis and severe atopy.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of ectodermal dysplasia. Clinical and genetic heterogeneity between different ectodermal dysplasia types and evidence of incomplete penetrance and variable expressivity increase the potential for misdiagnosis. We describe a family with X-linked hypohidrotic ectodermal dysplasia (XLHED) presenting with variable expressivity of symptoms between affected siblings. In addition to the classical signs of hypohidrosis, hypotrichosis and hypodontia, the index patient-a 5 year old boy, also presented with a severe atopy phenotype that was not observed in the other two affected brothers. Exome sequencing in the index and the mother identified a pathogenic nonsense variant in EDA (NM_001399.4: c.766 C>T; p. Gln256Ter). This study highlights how exome sequencing was crucial in establishing a precise molecular diagnosis of XLHED by enabling us to rule out other differential diagnoses including NEMO deficiency syndrome, that was initially presented as a clinical diagnosis to the family.

Poor Correlation of Oral Swabs with Esophageal Eosinophil Counts.

Eosinophilic esophagitis (EoE) is a chronic condition that requires repeated endoscopies/biopsies to track the disease and treatment response. This invasive procedure involves risk to the patient and has significant costs. We studied whether the detection of specific proteins (cytokines and eosinophil degranulation products) from oral swabs could serve as a minimally invasive test for EoE. Swabs of the oral cavity (buccal and oropharyngeal) were obtained prior to endoscopy/biopsies in patients with EoE, possible EoE, and non-EoE patients in addition to obtaining additional esophageal biopsy tissue. ELISAs measuring the levels of cytokines IL-5, IL-8, IL-13, and eosinophil degranulation products including major basic protein (MBP), eosinophil derived neurotoxin (EDN), and eosinophil peroxidase (EPO) were performed on the samples. Comparisons were made to peak esophageal eosinophil counts. Tolerability of the swabs was evaluated. 43 patients, 4-17 years old, participated in the study. Swabs were well tolerated and all showed measurable protein. 26 patients had EoE [14 active (> 15 eosinophils/high power field), 12 non-active], 17 patients did not have EoE. Results obtained from oral swabs showed poor correlation with those from esophageal tissue. Only measurement of eosinophil degranulation products EDN and EPO from esophageal tissues showed strong correlations with eosinophil counts. In this study, the levels of cytokines and eosinophil degranulation products detected from oral swabs did not correlate with esophageal eosinophilia, and their detection would be insufficient to displace endoscopy/biopsies.

IgE-Mediated allergy to wheat in a child with celiac disease - a case report.

INTRODUCTION: Celiac disease and immediate type hypersensitivity to wheat are immune responses with different pathogenic mechanisms. Both diseases are well known entities but their coexistence in the same patient is rarely reported. This is a unique case presentation of a patient with celiac disease who developed concomitant IgE-mediated wheat allergy and presented with immediate symptoms in two body systems. CASE PRESENTATION: We report the case of a girl with celiac disease who subsequently developed IgE-mediated hypersensitivity to wheat. The patient is a Caucasian female who was diagnosed with celiac disease at 18 months of age after presenting with recurrent vomiting and failure to thrive. Her anti-tTG antibody level was greater than 200 E.U. and biopsy results from endoscopy were consistent with celiac disease. Specific IgE antibody to wheat was negative at 2 years of age. Around seven years of age, she developed immediate symptoms of urticaria, cough and shortness of breath with accidental exposures to wheat. Specific IgE antibody testing was repeated and positive to wheat (42.5 kU/L), as well as rye (33.9 kU/L), barley (53.4 kU/L) and oat (11.3 kU/L). At 9 years of age, skin prick testing was positive to wheat, barley and rye but negative to oat. The patient has subsequently tolerated an open oral food challenge to oat. She continues to avoid wheat, rye and barley and carries an epinephrine autoinjector at all times. CONCLUSION: To our knowledge, this is the first report of a patient with celiac disease and concomitant IgE-mediated allergy to wheat presenting with immediate symptoms in two body systems. Although the pathophysiology of these diseases is different, this case demonstrates that they are not exclusive of one another. In patients who develop unexplained symptoms consistent with IgE-mediated allergy, an allergy assessment should be considered.