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Introduction: As the prevalence of food allergies (FAs) increases worldwide, our understanding of their pathophysiology and risk factors is markedly expanding. In the past few decades, an increasing number of genes have been linked to FA. Identification of such genes may help in predicting the genetic risk for FA development, age of onset, clinical manifestation, causative allergen(s), and possibly the optimal treatment strategies. Furthermore, identification of these genetic factors can help to understand the complex interactions between genes and the environment in predisposition to FA., Areas Covered: We outline the recent important progress in determining genetic variants and disease-associated genes in IgE-mediated FA. We focused on the monogenic inborn errors of immunity (IEI) where FA is one of the clinical manifestations, emphasizing the genes and gene variants, which were linked to FA with some of the most robust evidence., Expert Opinion: Genetics play a significant role, either directly or along with environmental factors, in the development of FA. As a multifactorial disease, it is expected that multiple genes and genetic loci contribute to the risk for FA development. Identification of the involved genes should contribute to the area of FA regarding pathogenesis, prediction, recognition, prognosis, prevention, and possibly therapeutic interventions.

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., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Several seeds have been increasingly incorporated in various food items, with consequent risk of hypersensitivity reactions that are often severe. Identification of the specific seed as the culprit is often not explored or is difficult to verify. In this article, we reviewed the English literature from January 1930 to March 2016 using PubMed and Google Scholar searching for publications relevant to hypersensitivity to common edible seeds, namely sesame, sunflower seed, poppy seed, pumpkin seed, flaxseed, and mustard seed. Considering the worldwide consumption of those seeds, the number of published articles on the subject was relatively small and was mainly as case reports rather than large series. Allergy to sesame was more reported than to other seeds, with an estimated prevalence of 0.1-0.2%. In this review, we summarize the information relevant to each of the six seeds and their oils regarding the manifestations, routes of exposure, identified major allergens, and cross-reactivity with other seeds or other foods. We also addressed the important role of a thorough history taking in suspecting seed allergy, the limited reliability of routine diagnostic procedures, and the importance of verification by appropriate challenge tests. At present, management is basically dietary avoidance and the use of symptomatic medications that may include epinephrine auto-injectors. We did not encounter any well-designed studies on immunotherapy for seed allergy, but it is hoped that such a gap be filled by the development of safe effective protocols in the near future., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To make recommendations based on a critical review of the evidence for the timing of the introduction of solid foods and its possible role in the development of food allergy., Data Sources: MEDLINE searches using the following search algorithm: [weaning AND infant AND allergy]/[food allergy AND sensitization]/[dietary prevention AND food allergy OR allergens]/[Jan 1980-Feb 2006]., Study Selection: Using the authors' clinical experience and research expertise, 52 studies were retrieved that satisfied the following conditions: English language, journal impact factor above 1 or scientific society, expert, or institutional publication, and appraisable using the World Health Organization categories of evidence., Results: Available information suggests that early introduction can increase the risk of food allergy, that avoidance of solids can prevent the development of specific food allergies, that some foods are more allergenic than others, and that some food allergies are more persistent than others., Conclusions: Pediatricians and allergists should cautiously individualize the introduction of solids into the infants' diet. With assessed risk of allergy, the optimal age for the introduction of selected supplemental foods should be 6 months, dairy products 12 months, hen's egg 24 months, and peanut, tree nuts, fish, and seafood at least 36 months. For all infants, complementary feeding can be introduced from the sixth month, and egg, peanut, tree nuts, fish, and seafood introduction require caution. Foods should be introduced one at a time in small amounts. Mixed foods containing various food allergens should not be given unless tolerance to every ingredient has been assessed.

Background: Ingestion is the principal route for food allergens, yet some highly sensitive patients may develop severe symptoms upon skin contact., Case Report: We describe five cases of severe food allergic reactions through skin contact, including inhalation in one., Methods: The cases were referred to a university allergy clinic, and evaluation comprised detailed medical history, physical examination, skin testing, serum total and specific IgE, and selected challenges., Results: These cases were found to have a strong family history of allergy, early age of onset, very high total serum IgE level, and strong reactivity to foods by skin prick testing or RAST. Interestingly, reactions occurred while all five children were being breast-fed (exclusively in four and mixed in one)., Conclusions: Severe food allergic reactions can occur from exposure to minute quantities of allergen by skin contact or inhalation. Food allergy by a noningestant route should be considered in patients with the above characteristics.

Objective: This presentation is designed to critically review information on presentations of food hypersensitivity reactions that may be considered unusual regarding the source or nature of allergen, route of exposure, or clinical manifestation., Data Sources: Information has been gathered primarily through a thorough search of the English literature relevant to human subjects. Some clinical cases were also included from the author's own clinical experience., Study Selection: Information summarized here was critically selected on the basis of proven or acceptable scientific validity., Results: The findings indicate that food allergy presentation can be unusual in three main aspects. First, the offending allergen may not be the obvious food that was ingested or be a food protein incorporated in a nonfood product. Second, systemic reactions can be provoked by very minute quantities of food allergens that may even get access through noningestant routes, eg, inhalation, odor, skin contact, or mucous membrane contact. Third, the clinical manifestations are not limited to the few gastrointestinal, cutaneous, and respiratory symptoms with which we are generally familiar., Conclusions: The extent of food allergy presentation is more than has been generally realized. Our awareness of such unusual presentations adds new knowledge and should prompt our interest in carefully evaluating patients with obscure allergic reactions for possible food allergy.

Because food allergy treatment is basically avoidance of the offending food(s), identification of the latter becomes the cornerstone for management. At present, the elimination-challenge test is the most definitive procedure for verification of a cause-and-effect relationship between a particular food and a certain reaction, allergic or not. The oral challenge test is most reliable when conducted in a double-blind, placebo-controlled manner. In routine clinical practice, however, single-blind testing is satisfactory in most cases. Open challenge testing might be acceptable in young children or for screening the least suspected foods. It would be prudent to avoid the test, in any of its forms, in instances where a specific food caused a life-threatening reaction. Caution needs to be practiced in planning, conducting, and interpreting the results of challenge tests. Difficulties may be encountered in disguising the test food, choosing a placebo, reproducing the natural exposure, incorporation of possible associated factors, and avoiding any bias on the patient's or observer's part.

The past few decades have witnessed an increasing understanding of the role of food allergy in human disease. Nevertheless, controversies still exist in several aspects of this area. One such controversy concerns the body systems that can be the target of food hypersensitivity reactions. Another is the role of noningestant exposure to food in a nonoccupational setting. Both of these aspects are vividly demonstrated in the case presented here.

The role of food allergy in the respiratory tract is often underestimated. A wide variety of food-induced respiratory symptoms has been described. In some patients, a food additive rather than a food protein is the offending agent. This presentation focuses on food-induced asthma and milk-induced chronic pulmonary disease in infants.

Food allergy is one of several causes of adverse reactions to foods. The underlying immunologic mechanism varies from one manifestation to another, hence no current single laboratory test can be expected to be positive in every case. The diagnosis could be suggested by information gathered from the medical history or screening procedures, such as trials of elimination diets, the food/symptom diary, skin testing, and in vitro-specific IgE antibody measurement. All foods suspected by any of the aforementioned methods should be subjected to verification by appropriate elimination-challenge testing, preferably in a double-blind, placebo-controlled manner. Basically, treatment is dietary elimination, and its success requires identification and avoidance of all offending foods and control of other contributory factors.

Interest in food allergy has increased among physicians as well as the public. The symptoms are mainly in the gastrointestinal tract, the skin, and the respiratory system. Other organs are less commonly affected. The offending food can be suspected from the medical history, by skin testing, or by serum-specific IgE antibodies (RAST). Verification, however, depends on documentation of disappearance of symptoms after avoidance of the offending food and their recurrence on reintroduction of that food. Treatment is mainly dietary avoidance. Its success, however, depends on many factors. Pharmacologic agents may be needed in some cases for symptomatic relief and possibly for prophylaxis. The awareness on the part of the primary physician of the manifestations of food allergy and its diagnosis should enhance the physician's expertise in dealing with such patients regarding further management.

The increasing awareness by the medical profession, as well as the public, of food allergy imposes the parallel task of accurate diagnosis and proper treatment. A carefully obtained medical history and a properly conducted elimination-challenge test are the most valuable as well as the least expensive procedures for diagnosis. Other selected in vivo and in vitro tests may enhance the diagnostic ability and may verify the immunologic basis of the food-induced reaction. Treatment is basically dietary avoidance, and its success depends on several factors. Pharmacologic agents may be needed for symptomatic treatment, and in certain instances for prophylaxis. The need still exists for developing an effective procedure of hyposensitization.

To date the most reliable procedure for the diagnosis of milk hypersensitivity is a properly conducted elimination-challenge test. Several in vitro tests have been developed but because of the diverse underlying mechanisms of hypersensitivity reactions to milk developing a single laboratory test that can be universally positive in every patient would be rather difficult. However, with a better categorization of milk-sensitive patients, together with the development of relevant, standardized and practical tests, the laboratory diagnosis of milk allergy should become more reliable. Milk hypersensitivity can be effectively treated and is largely preventable. Avoidance is the most effective mode of treatment and results in a good prognosis. In instances where the desired degree of avoidance cannot be attained pharmacologic agents may be of help. The need still exists for developing an effective procedure of hyposensitization. For prevention, prolonged breast feeding should be recommended, especially in infants of atopic families.

The mainstay of successful management of food allergy is the identification of the offending food(s), as verified by the elimination-challenge test. Dietary elimination is the most effective and inexpensive method, but its success depends on several factors. Initially, dietary elimination may need to be strict, but later certain patients may discover that they can tolerate limited quantities or certain preparations of the offending food without significant symptoms. In certain cases, provision of a substitute or a nutritional supplement may be needed. Food allergy in infants who are exclusively breast-fed requires elimination of the offending food from the mother's diet. Because of cross-antigenicity, certain patients may also need to avoid other members of the food family. This phenomenon is especially noticeable among seafoods. In certain patients who have mild to moderate sensitivity to multiple foods that cannot be completely avoided, rotation diets may be both effective and more convenient. In a few patients, conventional elimination diets may be followed for limited time periods until all offending foods are identified. In addition to symptomatic treatment, pharmacologic agents may be taken for prophylaxis. Antihistamines, oral cromolyn and possibly other medications, when taken before an anticipated exposure or on a regular basis, may prevent or minimize the symptoms in certain patients. At present, no adequate evidence supports the use of hyposensitization therapy with food extracts. The prognosis of food allergy is more favorable in children than in adults. Most food-sensitive infants and young children will tolerate the offending food after 1-2 years of avoidance.

Milk hypersensitivity is a problem that can have substantial health, financial and social implications. The condition is underdiagnosed by some physicians and overdiagnosed by others probably because its symptoms are varied and shared with many other diseases. The gap in our knowledge on the pathogenesis of various manifestations of CMA has been only partly bridged by the information accumulated in recent years. It has become clear that milk-sensitive patients are heterogeneous, both regarding symptomatology and underlying pathogenic mechanisms.

Food sensitivity is only one of several types of food-related reactions. Symptoms are not pathognomonic; hence, a broad differential diagnosis is often considered. Unless the anticipated reaction is systemic anaphylaxis, the role of any food suspected (by history, skin testing, and/or radioallergosorbent test) of causing the patient's symptoms should be verified by elimination-challenge testing. Dietary elimination is the most effective treatment, but its success depends on several factors.