Food allergy is an important public health problem that affects children and adults and may be increasing in prevalence. Despite the risk of severe allergic reactions and even death, there is no current treatment for food allergy: the disease can only be managed by allergen avoidance or treatment of symptoms. The diagnosis and management of food allergy also may vary from one clinical practice setting to another. Finally, because patients frequently confuse nonallergic food reactions, such as food intolerance, with food allergies, there is an unfounded belief among the public that food allergy prevalence is higher than it truly is. In response to these concerns, the National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy. These Guidelines are intended for use by a wide variety of health care professionals, including family practice physicians, clinical specialists, and nurse practitioners. The Guidelines include a consensus definition for food allergy, discuss comorbid conditions often associated with food allergy, and focus on both IgE-mediated and non-IgE-mediated reactions to food. Topics addressed include the epidemiology, natural history, diagnosis, and management of food allergy, as well as the management of severe symptoms and anaphylaxis. These Guidelines provide 43 concise clinical recommendations and additional guidance on points of current controversy in patient management. They also identify gaps in the current scientific knowledge to be addressed through future research.

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Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report

Methods We randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test — one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age. Results Among the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P<0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P = 0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy. Conclusions The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00329784.)

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Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy

This review focuses on advances and updates in the epidemiology, pathogenesis, diagnosis, and treatment of food allergy over the past 3 years since our last comprehensive review. On the basis of numerous studies, food allergy likely affects nearly 5% of adults and 8% of children, with growing evidence of an increase in prevalence. Potentially rectifiable risk factors include vitamin D insufficiency, unhealthful dietary fat, obesity, increased hygiene, and the timing of exposure to foods, but genetics and other lifestyle issues play a role as well. Interesting clinical insights into pathogenesis include discoveries regarding gene-environment interactions and an increasing understanding of the role of nonoral sensitizing exposures causing food allergy, such as delayed allergic reactions to carbohydrate moieties in mammalian meats caused by sensitization from homologous substances transferred during tick bites. Component-resolved diagnosis is being rapidly incorporated into clinical use, and sophisticated diagnostic tests that indicate severity and prognosis are on the horizon. Current management relies heavily on avoidance and emergency preparedness, and recent studies, guidelines, and resources provide insight into improving the safety and well-being of patients and their families. Incorporation of extensively heated (heat-denatured) forms of milk and egg into the diets of children who tolerate these foods, rather than strict avoidance, represents a significant shift in clinical approach. Recommendations about the prevention of food allergy and atopic disease through diet have changed radically, with rescinding of many recommendations about extensive and prolonged allergen avoidance. Numerous therapies have reached clinical trials, with some showing promise to dramatically alter treatment. Ongoing studies will elucidate improved prevention, diagnosis, and treatment.

https://www.jacionline.org/article/S0091-6749(13)01836-8/pdf

Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence-based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non-life-threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/all.12429

EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy

Background: Several indicators suggest that food allergy in infants is common and possibly increasing. Few studies have used oral food challenge to measure this phenomenon at the population level. Objective: To measure the prevalence of common IgE-mediated childhood food allergies in a population-based sample of 12-month-old infants by using predetermined food challenge criteria to measure outcomes. Methods: A sampling frame was used to select recruitment areas to attain a representative population base. Recruitment occurred at childhood immunization sessions in Melbourne, Australia. Infants underwent skin prick testing, and those with any sensitization (wheal size ≥1 mm) to 1 or more foods (raw egg, peanut, sesame, shellfish, or cow's milk) were invited to attend an allergy research clinic. Those who registered a wheal size ≥1 mm to raw egg, peanut, or sesame underwent oral food challenge. Results: Amongst 2848 infants (73% participation rate), the prevalence of any sensitization to peanut was 8.9% (95% CI, 7.9-10.0); raw egg white, 16.5% (95% CI, 15.1-17.9); sesame, 2.5% (95% CI, 2.0-3.1); cow's milk, 5.6% (95% CI, 3.2-8.0); and shellfish, 0.9% (95% CI, 0.6-1.5). The prevalence of challenge-proven peanut allergy was 3.0% (95% CI, 2.4-3.8); raw egg allergy, 8.9% (95% CI, 7.8-10.0); and sesame allergy, 0.8% (95% CI, 0.5-1.1). Oral food challenges to cow's milk and shellfish were not performed. Of those with raw egg allergy, 80.3% could tolerate baked egg. Conclusion: More than 10% of 1-year-old infants had challenge-proven IgE-mediated food allergy to one of the common allergenic foods of infancy. The high prevalence of allergic disease in Australia requires further investigation and may be related to modifiable environmental factors.

https://www.jacionline.org/article/S0091-6749(11)00135-7/pdf

Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants.

Background Despite guidelines recommending avoidance of peanuts during infancy in the United Kingdom (UK), Australia, and, until recently, North America, peanut allergy (PA) continues to increase in these countries. Objective We sought to determine the prevalence of PA among Israeli and UK Jewish children and evaluate the relationship of PA to infant and maternal peanut consumption. Methods A clinically validated questionnaire determined the prevalence of PA among Jewish schoolchildren (5171 in the UK and 5615 in Israel). A second validated questionnaire assessed peanut consumption and weaning in Jewish infants (77 in the UK and 99 in Israel). Results The prevalence of PA in the UK was 1.85%, and the prevalence in Israel was 0.17% (P Conclusions We demonstrate that Jewish children in the UK have a prevalence of PA that is 10-fold higher than that of Jewish children in Israel. This difference is not accounted for by differences in atopy, social class, genetic background, or peanut allergenicity. Israeli infants consume peanut in high quantities in the first year of life, whereas UK infants avoid peanuts. These findings raise the question of whether early introduction of peanut during infancy, rather than avoidance, will prevent the development of PA.

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Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy

milk protein of a camel, pig or zebra [7]. We noted that those animals with the more closely related casein genes (i.e., the goat, sheep, cow, deer, pronghorn, buffalo) are “kosher” animals, while the camel, mare and pig represented “non-kosher” animals. “Kosher” animals are listed in the Old Testament (Leviticus 11) as animals that the Jews are allowed to eat, and are generally described as animals that have split hooves (artiodactyls) and chew their cud (ruminants). We examined the hypothesis that once an individual is allergic to cow’s milk protein, he or she is sensitized to milk from all kosher animals but not to milk from non-kosher animals. In the present study we examined the sensitization to milk from ibex, deer and pig among 24 patients with cow’s milk allergy. The ibex and deer are kosher but the pig is not.

Cross-sensitization between milk proteins: reactivity to a "kosher" epitope?

Background A family history of atopy has been considered an independent risk factor for atopic diseases in children. Objective To relate the risk of an infant developing IgE-mediated cow's milk allergy (IgE-CMA) to the atopic status of parents. Methods Assessment of the parental atopic status of children with IgE-CMA (n = 66) previously identified in a large-scale prospective study was compared with the parental atopic status of a control group of healthy infants (n = 156). The atopic status was identified both by self-reporting and skin prick tests (SPTs). Results Analysis for the risk for infants to develop IgE-CMA depended on the assessment method used. No significant differences were noted in self-reported parental atopic status between the IgE-CMA patients and the control group. However, among the subgroup of infants with persistent IgE-CMA (n = 25), maternal but not paternal self-reporting for atopy was more likely compared with parents of the control group ( P  = .04). In contrast, when analyzed by SPT, in both this persistent subgroup and the total allergic cohort, no significant differences were noted whether analyzed by single parent or both parents and whether the parent tested singly or multiply positive on the SPT. Conclusion In families with children with persistent IgE-CMA, self-reporting of atopy by parents may be biased. Furthermore, the demonstration of IgE-mediated responses to allergens in parents is insufficient by itself, in a general population cohort, to predict which infants are at greatest risk of developing IgE-CMA.

Role of parental atopy in cow's milk allergy: a population-based study.

Recent evidence from mouse models indicates that neonatal exposure to lipopolysaccharide (LPS) can prevent experimentally induced allergic disease. Furthermore, we noted that human cord blood mononuclear cells (CBMC) have an increased proliferative response to LPS relative to their respective maternal peripheral blood mononuclear cells (PBMC). We sought, therefore, to examine the cytokine expression profile induced by LPS in CBMC and its relationship to the LPS-mediated proliferative response. CBMC and maternal PBMC were evaluated for IL-10, IL-4, IL-13, IL-12α, and IFN-γ expression after LPS stimulation by real-time PCR. IFN-γ secretion was detected by enzyme-linked immunosorbent assay. LPS increased IFN-γ and IL-13, but decreased IL-4 expression in CBMC (P < 0.024, P < 0.014, and P < 0.027, respectively). In PBMC, however, no significant changes in expression were noted after LPS stimulation. Stimulation by LPS significantly increased the secretion of IFN-γ in CBMC compared with PBMC at the two concentr...

https://www.atsjournals.org/doi/pdf/10.1165/rcmb.2007-0143OC

Correlation of Th1-Type Cytokine Expression and Induced Proliferation to Lipopolysaccharide

Despite an attenuated proliferative response in human cord blood mononuclear cells (CBMCs) to activation of its TCR in vitro, the neonate is capable of mounting a mature T(h)1-type response to BCG vaccination. We hypothesized that in the context of other innate triggers, activation of the TCR can be restored. In order to test this hypothesis, we analyzed CBMC response to LPS, with LPS serving as a surrogate activator of the innate system. We performed proliferative assays on 34 maternal-neonatal pairs of PBMCs and CBMCs, respectively. In all, 30/34 (88%) of CBMCs proliferated in response to LPS (10 microg ml(-1), P < 2.7 x 10(-7)), in contrast to only 10/32 (31%) of their respective maternally derived PBMCs, despite having a comparatively greater response to PHA than did their CBMC counterparts (P < 0.0002). LPS synergized with immobilized anti-human CD3epsilon mAb (1.25-10 microg ml(-1)) to augment the proliferative response in CBMCs but failed to do so in maternally derived PBMCs. LPS responsiveness and its synergy with activation of the TCR in CBMCs were independent of accessory cells. These results are the first evidence that LPS and anti-CD3 mAb are synergistic, demonstrating a critical link between the innate and adaptive immune systems.

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Galia Zadik-Mnuhin

Papers

Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy

Cross-sensitization between milk proteins: reactivity to a "kosher" epitope?

Role of parental atopy in cow's milk allergy: a population-based study.

Correlation of Th1-Type Cytokine Expression and Induced Proliferation to Lipopolysaccharide

Synergy between LPS and immobilized anti-human CD3ϵ mAb for activation of cord blood CD3+ T cells