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.
Hippocrates is often credited with first recognizing that food could be responsible for adverse symptoms and even death in some individuals, but it was not until the seminal observations by Prausnitz ...that the investigation of food allergy was viewed on a more scientific basis. In the first half of the 20th century, there were periodic reports in the medical literature describing various food allergic reactions. In the mid- to late- 1970's, the studies of Charles May and colleagues began to penetrate the medical world's skepticism about the relevance of food allergy and how to diagnose it, since standard skin testing was known to correlate poorly with clinical symptoms. With May's introduction of the double-blind placebo-controlled oral food challenge, the study of food allergy became evidence-based and exponential strides have been made over the past four decades in the study of basic immunopathogenic mechanisms and natural history, and the diagnosis and management of food allergies. Today IgE- and non-IgE-mediated food allergic disorders are well characterized and efforts to treat these allergies by various immunotherapeutic strategies are well under way.
This review provides general information to serve as a primer for those embarking on understanding food allergy and also details advances and updates in epidemiology, pathogenesis, diagnosis, and ...treatment that have occurred over the 4 years since our last comprehensive review. Although firm prevalence data are lacking, there is a strong impression that food allergy has increased, and rates as high as approximately 10% have been documented. Genetic, epigenetic, and environmental risk factors are being elucidated increasingly, creating potential for improved prevention and treatment strategies targeted to those at risk. Insights on pathophysiology reveal a complex interplay of the epithelial barrier, mucosal and systemic immune response, route of exposure, and microbiome among other influences resulting in allergy or tolerance. The diagnosis of food allergy is largely reliant on medical history, tests for sensitization, and oral food challenges, but emerging use of component-resolved diagnostics is improving diagnostic accuracy. Additional novel diagnostics, such as basophil activation tests, determination of epitope binding, DNA methylation signatures, and bioinformatics approaches, will further change the landscape. A number of prevention strategies are under investigation, but early introduction of peanut has been advised as a public health measure based on existing data. Management remains largely based on allergen avoidance, but a panoply of promising treatment strategies are in phase 2 and 3 studies, providing immense hope that better treatment will be imminently and widely available, whereas numerous additional promising treatments are in the preclinical and clinical pipeline.
Immunology of Food Allergy Tordesillas, Leticia; Berin, M. Cecilia; Sampson, Hugh A.
Immunity (Cambridge, Mass.),
07/2017, Volume:
47, Issue:
1
Journal Article
Peer reviewed
Open access
Many consider food allergy as the “second wave” of the allergy epidemic following the “first wave” of respiratory allergy, i.e., asthma and allergic rhinitis, plaguing westernized countries, with up ...to 8% of young children and 2%–3% of adults in the United States now affected by hypersensitivity reactions to various foods. In the past decade, there have been great strides in our understanding of the underlying immunopathogenesis of these disorders, which have led to improved diagnostic techniques, management strategies, and therapeutic approaches. Here we will review the most recent understanding of basic mechanisms underlying IgE-mediated food allergies and novel therapeutic approaches under investigation for both the prevention and treatment of IgE-mediated food allergies.
Food allergies have increased exponentially in the last decades. Tordesillas et al. review the immune mechanisms of sensitization to foods and recent developments in the prevention of food allergies. In addidtion, they discuss efficacy of antigen-specific immunotherapies as well as other emerging therapeutic approaches.
Food allergies are increasing in prevalence at a higher rate than can be explained by genetic factors, suggesting a role for as yet unidentified environmental factors. In this review, we summarize ...the state of knowledge about the healthy immune response to antigens in the diet and the basis of immune deviation that results in immunoglobulin E (IgE) sensitization and allergic reactivity to foods. The intestinal epithelium forms the interface between the external environment and the mucosal immune system, and emerging data suggest that the interaction between intestinal epithelial cells and mucosal dendritic cells is of particular importance in determining the outcome of immune responses to dietary antigens. Exposure to food allergens through non-oral routes, in particular through the skin, is increasingly recognized as a potentially important factor in the increasing rate of food allergy. There are many open questions on the role of environmental factors, such as dietary factors and microbiota, in the development of food allergy, but data suggest that both have an important modulatory effect on the mucosal immune system. Finally, we discuss recent developments in our understanding of immune mechanisms of clinical manifestations of food allergy. New experimental tools, particularly in the field of genomics and the microbiome, are likely to shed light on factors responsible for the growing clinical problem of food allergy.
Food allergy Sicherer, Scott H., MD; Sampson, Hugh A., MD
Journal of allergy and clinical immunology,
02/2010, Volume:
125, Issue:
2
Journal Article
Peer reviewed
Adverse immune responses to foods affect approximately 5% of young children and 3% to 4% of adults in westernized countries and appear to have increased in prevalence. Food-induced allergic reactions ...are responsible for a variety of symptoms and disorders involving the skin and gastrointestinal and respiratory tracts and can be attributed to IgE-mediated and non–IgE-mediated (cellular) mechanisms. Genetic disposition and environmental factors might abrogate oral tolerance, leading to food allergy. Disease outcomes are influenced by the characteristics of the immune response and of the triggering allergen. Diagnosis is complicated by the observation that detection of food-specific IgE (sensitization) does not necessarily indicate clinical allergy. Therefore diagnosis requires a careful medical history, laboratory studies, and, in many cases, an oral food challenge to confirm a diagnosis. Novel diagnostic methods, including ones that focus on immune responses to specific food proteins or epitopes of specific proteins, are under study. Currently, management of food allergies consists of educating the patient to avoid ingesting the responsible allergen and to initiate therapy (eg, with injected epinephrine for anaphylaxis) in case of an unintended ingestion. Improved therapeutic strategies under study include oral and sublingual immunotherapy, Chinese herbal medicine, anti-IgE antibodies, and modified vaccines.
In this rostrum we aim to increase awareness of anaphylaxis in infancy in order to improve clinical diagnosis, management, and prevention of recurrences. Anaphylaxis is increasingly reported in this ...age group. Foods are the most common triggers. Presentation typically involves the skin (generalized urticaria), the respiratory tract (cough, wheeze, stridor, and dyspnea), and/or the gastrointestinal tract (persistent vomiting). Tryptase levels are seldom increased because of infant anaphylaxis, although baseline tryptase levels can be increased in the first few months of life, reflecting mast cell burden in the developing immune system. The differential diagnosis of infant anaphylaxis includes consideration of age-unique entities, such as food protein–induced enterocolitis syndrome with acute presentation. Epinephrine (adrenaline) treatment is underused in health care and community settings. No epinephrine autoinjectors contain an optimal dose for infants weighing 10 kg or less. After treatment of an anaphylactic episode, follow-up with a physician, preferably an allergy/immunology specialist, is important for confirmation of anaphylaxis triggers and prevention of recurrences through avoidance of confirmed specific triggers. Natural desensitization to milk and egg can occur. Future research should include validation of the clinical criteria for anaphylaxis diagnosis in infants, prospective longitudinal monitoring of baseline serum tryptase levels in healthy and atopic infants during the first year of life, studies of infant comorbidities and cofactors that increase the risk of severe anaphylaxis, development of autoinjectors containing a 0.1-mg epinephrine dose suitable for infants, and inclusion of infants in prospective studies of immune modulation to prevent anaphylaxis recurrences.
Background Peanut allergy is common, life-threatening, and without therapeutic options. We evaluated peanut epicutaneous immunotherapy (EPIT) by using Viaskin Peanut for peanut allergy treatment. ...Objective We sought to evaluate the clinical, safety, and immunologic effects of EPIT for the treatment of peanut allergy. Methods In this multicenter, double-blind, randomized, placebo-controlled study, 74 participants with peanut allergy (ages 4-25 years) were treated with placebo (n = 25), Viaskin Peanut 100 μg (VP100; n = 24) or Viaskin Peanut 250 μg (VP250; n = 25; DBV Technologies, Montrouge, France). The primary outcome was treatment success after 52 weeks, which was defined as passing a 5044-mg protein oral food challenge or achieving a 10-fold or greater increase in successfully consumed dose from baseline to week 52. Adverse reactions and mechanistic changes were assessed. Results At week 52, treatment success was achieved in 3 (12%) placebo-treated participants, 11 (46%) VP100 participants, and 12 (48%) VP250 participants ( P = .005 and P = .003, respectively, compared with placebo; VP100 vs VP250, P = .48). Median change in successfully consumed doses were 0, 43, and 130 mg of protein in the placebo, VP100, and VP250 groups, respectively (placebo vs VP100, P = .014; placebo vs VP250, P = .003). Treatment success was higher among younger children ( P = 0.03; age, 4-11 vs >11 years). Overall, 14.4% of placebo doses and 79.8% of VP100 and VP250 doses resulted in reactions, predominantly local patch-site and mild reactions ( P = .003). Increases in peanut-specific IgG4 levels and IgG4 /IgE ratios were observed in peanut EPIT-treated participants, along with trends toward reduced basophil activation and peanut-specific TH 2 cytokines. Conclusions Peanut EPIT administration was safe and associated with a modest treatment response after 52 weeks, with the highest responses among younger children. This, when coupled with a high adherence and retention rate and significant changes in immune pathways, supports further investigation of this novel therapy.
Background Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated food allergy. FPIES diagnosis is frequently delayed because of the absence of classic allergic symptoms and lack ...of biomarkers. Objective We sought to characterize the clinical features and resolution of FPIES in patients evaluated in our practice. Methods Subjects 6 months to 45 years of age with FPIES were prospectively recruited for oral food challenges (OFCs). Medical records were searched to identify the subjects who did not participate in OFCs. Results Among 160 subjects, 54% were male; median age at diagnosis was 15 months. We performed 180 OFCs to 15 foods in 82 subjects; 30% of the study population had FPIES confirmed based on OFC results. The most common foods were cow's milk (44%), soy (41%), rice (22.5%), and oat (16%). The majority (65%) reacted to 1 food, 26% reacted to 2 foods, and 9% reacted to 3 or more foods. The majority were atopic, and 39% had IgE sensitization to another food. Thirty-nine (24%) subjects had positive specific IgE levels to the food inducing FPIES. Among children with specific IgE to cow's milk, 41% changed from a milk FPIES to an IgE-mediated phenotype over time. The median age when tolerance was established was 4.7 years for rice, 4 years for oat, and 6.7 years for soy. Median age when milk tolerance was established for subjects with undetectable milk-specific IgE levels was 5.1 years, whereas none of the subjects with detectable milk-specific IgE became tolerant to milk during the study ( P = .003). Conclusion FPIES typically resolves by age 5 years. Milk FPIES, especially with detectable food-specific IgE, can have a protracted course and eventually transition to acute reactions.
Food allergy is increasingly common in children, affecting about 4%‐8%. The mainstays of management remain allergen avoidance and emergency preparedness to treat allergic reactions with emergency ...medications. Unfortunately, these approaches are unsatisfactory for many patients and their families as the restrictions, constant vigilance, and unpredictable severity of allergic reactions negatively impact quality of life. In recent decades, there has been significant interest in developing treatments for food allergy that lead to desensitization to increase thresholds for triggering allergic reactions and decrease the risk of reacting to allergen‐contaminated food products. Epicutaneous immunotherapy (EPIT) is a novel therapy that is currently under investigation, delivering allergen via repeated applications to the skin and targeting antigen‐presenting cells in the superficial skin layers. Murine models have demonstrated that allergen uptake is an active process by skin dendritic cells with subsequent migration to draining lymph nodes. Allergen exposure to the non‐vascularized epidermis limits systemic absorption, contributing to the high‐safety profile. Results from murine experiments showed that EPIT has comparable efficacy as subcutaneous immunotherapy in terms of challenge outcomes, airway hyper‐responsiveness, and immunologic parameters. Several clinical trials of EPIT have recently been completed or are ongoing. Results support the high safety and tolerability of this approach. Efficacy data suggest that the change in threshold eliciting dose following 1 year of therapy is less than that seen compared to high‐dose (2‐4 g peanut protein) oral immunotherapy, but more prolonged treatment with EPIT appears to lead to increasing desensitization. Additional data from larger‐scale studies should provide a more robust assessment of safety and efficacy of EPIT.
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