Eosinophilic esophagitis (EoE) is a clinicopathologic condition of increasing recognition and prevalence. In 2007, a consensus recommendation provided clinical and histopathologic guidance for the diagnosis and treatment of EoE; however, only a minority of physicians use the 2007 guidelines, which require fulfillment of both histologic and clinical features. Since 2007, the number of EoE publications has doubled, providing new disease insight. Accordingly, a panel of 33 physicians with expertise in pediatric and adult allergy/immunology, gastroenterology, and pathology conducted a systematic review of the EoE literature (since September 2006) using electronic databases. Based on the literature review and expertise of the panel, information and recommendations were provided in each of the following areas of EoE: diagnostics, genetics, allergy testing, therapeutics, and disease complications. Because accumulating animal and human data have provided evidence that EoE appears to be an antigen-driven immunologic process that involves multiple pathogenic pathways, a new conceptual definition is proposed highlighting that EoE represents a chronic, immune/antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. The diagnostic guidelines continue to define EoE as an isolated chronic disorder of the esophagus diagnosed by the need of both clinical and pathologic features. Patients commonly have high rates of concurrent allergic diatheses, especially food sensitization, compared with the general population. Proved therapeutic options include chronic dietary elimination, topical corticosteroids, and esophageal dilation. Important additions since 2007 include genetic underpinnings that implicate EoE susceptibility caused by polymorphisms in the thymic stromal lymphopoietin protein gene and the description of a new potential disease phenotype, proton pump inhibitor-responsive esophageal eosinophila. Further advances and controversies regarding diagnostic methods, surrogate disease markers, allergy testing, and treatment approaches are discussed.
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.
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.
Food protein-induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available.
This clinical report reviews the nutritional options during pregnancy, lactation, and the first year of life that may affect the development of atopic disease (atopic dermatitis, asthma, food allergy) in early life.
BACKGROUND
For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy.
METHODS
In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months.
RESULTS
After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months.
CONCLUSIONS
These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.)
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