Evolution of Guidelines on Peanut Allergy and Peanut Introduction in Infants: A Review.

Importance: The reported prevalence of peanut allergy among children in the United States has increased more than 3-fold in the last 20 years. Medical guidelines on the introduction of peanut as well as other allergenic foods have evolved with the emerging evidence that an early introduction to these foods is more beneficial than a delayed introduction. This review highlights the studies that have led to the evolving guidelines on peanut introduction in infants. Observations: The prevalence of peanut allergy has increased despite the publication of guidelines from the American Academy of Pediatrics in 2000, which recommended a delayed introduction of peanut. Since the 2000 guidelines, studies have provided evidence to support an earlier rather than delayed introduction. As a result, the American Academy of Pediatrics updated their guidelines in 2008 to promote peanut introduction during infancy. Current evidence continues to support the benefits of an earlier rather than delayed introduction. Conclusions and Relevance: Over the years, guidelines on the introduction of peanut have evolved, and recent literature suggests that an earlier rather than delayed introduction is beneficial to prevent peanut allergies in infants.

Interpreting IgE sensitization tests in food allergy.

Food allergies are increasing in prevalence, and with it, IgE testing to foods is becoming more commonplace. Food-specific IgE tests, including serum assays and prick skin tests, are sensitive for detecting the presence of food-specific IgE (sensitization), but specificity for predicting clinical allergy is limited. Therefore, positive tests are generally not, in isolation, diagnostic of clinical disease. However, rationale test selection and interpretation, based on clinical history and understanding of food allergy epidemiology and pathophysiology, makes these tests invaluable. Additionally, there exist highly predictive test cutoff values for common allergens in atopic children. Newer testing methodologies, such as component resolved diagnostics, are promising for increasing the utility of testing. This review highlights the use of IgE serum tests in the diagnosis of food allergy.

Risk factors in pediatric shrimp allergy.

BACKGROUND: The prevalence of shellfish allergy is ∼1.3% in the United States, with shrimp most commonly reported. Shellfish is one of the top causes of food-induced anaphylactic reactions, yet there are no reported rates of pediatric shrimp anaphylaxis in the literature. In previously reported adults with shrimp allergy, the rate of anaphylaxis to shrimp was 42%. OBJECTIVE: To describe the rate of anaphylaxis among children with shrimp allergy, demographics, clinical presentation, and cross-reactive sensitization. METHODS: Retrospective chart review of children ≤18 years old who presented with shrimp allergy to Texas Children's Hospital Allergy and Immunology Clinic over 11 years. RESULTS: Sixty-eight patients were identified with shrimp allergy (61% male, 39% female), with a median age of diagnosis at 5.6 years (range, 0.96-16.6 years). The rate of anaphylaxis was 12%, and mucocutaneous symptoms were most common (skin symptoms, 70%; urticaria, 58%; and angioedema, 58%). No factors were positively associated with anaphylaxis, whereas patients without anaphylaxis had a significantly higher rate of eczema compared with those with anaphylaxis (p = 0.02). African Americans and Asian Americans were disproportionately affected (p < 0.001). There were low rates of cross-sensitization for other crustaceans and for mollusks (57% and 26%, respectively). CONCLUSION: The rate of anaphylaxis to shrimp was significantly lower in children with shrimp allergy than in adults, and anaphylactic reactions were negatively associated with eczema. Cross-reactivity to other crustaceans and mollusks does not uniformly occur. Prospective studies with double blinded placebo-controlled food challenges are needed to further characterize patients with shrimp allergy.

Molecular diagnosis of egg allergy: an update.

Hen's egg allergy affects up to 2.5% of young children and is potentially life-threatening. Several phenotypes of egg allergy have been identified, including those who tolerate extensively heated egg in bakery products. Diagnosis and monitoring for resolution often requires oral food challenges, which can result in anaphylaxis. Newer approaches, such as component-resolved diagnostics, microarray analysis and epitope mapping, are being evaluated to determine if these strategies can replace or reduce the need for oral food challenges. Studies suggest that elevated levels of ovomucoid IgE indicate an inability to tolerate extensively heated forms of egg. Egg protein-specific IgE/IgG4 ratios may be helpful in predicting tolerance. Additionally, patients with conformational epitopes to hen's egg are more likely to resolve their allergy compared with those with IgE binding to sequential epitopes. The pairing of microarray technology to epitope mapping is a potential tool to improve diagnosis. This review examines the current body of literature on these tools.

PGM3 mutations cause a congenital disorder of glycosylation with severe immunodeficiency and skeletal dysplasia.

Human phosphoglucomutase 3 (PGM3) catalyzes the conversion of N-acetyl-glucosamine (GlcNAc)-6-phosphate into GlcNAc-1-phosphate during the synthesis of uridine diphosphate (UDP)-GlcNAc, a sugar nucleotide critical to multiple glycosylation pathways. We identified three unrelated children with recurrent infections, congenital leukopenia including neutropenia, B and T cell lymphopenia, and progression to bone marrow failure. Whole-exome sequencing demonstrated deleterious mutations in PGM3 in all three subjects, delineating their disease to be due to an unsuspected congenital disorder of glycosylation (CDG). Functional studies of the disease-associated PGM3 variants in E. coli cells demonstrated reduced PGM3 activity for all mutants tested. Two of the three children had skeletal anomalies resembling Desbuquois dysplasia: short stature, brachydactyly, dysmorphic facial features, and intellectual disability. However, these additional features were absent in the third child, showing the clinical variability of the disease. Two children received hematopoietic stem cell transplantation of cord blood and bone marrow from matched related donors; both had successful engraftment and correction of neutropenia and lymphopenia. We define PGM3-CDG as a treatable immunodeficiency, document the power of whole-exome sequencing in gene discoveries for rare disorders, and illustrate the utility of genomic analyses in studying combined and variable phenotypes.