Eosinophilic oesophagitis (EoE) is an antigen-driven pan-oesophagitis that is defined by the presence of at least 15 eosinophils per high power field on oesophageal histology in conjunction with upper gastrointestinal symptoms. EoE is closely associated with atopic disorders, in particular with food allergy, and as for other atopic diseases in childhood, there is a strong preponderance of male patients who have this disorder. The mechanisms leading to EoE have been characterised at the molecular level. Eotaxin-3, interleukin-5 and interleukin-13 are the key effector molecules in EoE pathogenesis. EoE presents with a diverse range of gastrointestinal symptoms, including regurgitation, vomiting, feeding difficulties or feeding refusal in infancy, as well as heartburn, dysphagia and food bolus impaction in older children and adults. The diagnosis may also be ascertained as an incidental finding in patients undergoing gastroscopy for other suspected conditions, including coeliac disease. EoE is different from gastro-oesophageal reflux disease and does not improve in response to proton pump inhibitors. Therefore, EoE needs to be distinguished from so-called PPI-responsive oesophageal eosinophilia. The long-term prognosis of EoE remains poorly defined, and complications mainly relate to subepithelial remodelling and fibrosis that may result in dysmotility, dysphagia and oesophageal strictures. The treatment of EoE involves elimination diets and topical swallowed aerosolised corticosteroids, while biological therapies targeting molecular mechanisms have so far been unsuccessful. In children, elemental diets have proved highly effective, but multiple food elimination diets are more sustainable in the long term. Further randomised, controlled trials on dietary or pharmacological interventions are needed to inform the optimal long-term management of EoE.
Food allergy is a known trigger of anaphylaxis. Although the awareness of food allergies has improved, food-related allergic reactions and anaphylaxis still commonly occur. The recognition of anaphylaxis, its prompt treatment, and patient education are important for the prevention of future food reactions. Patients and health care providers should also recognize the importance of epinephrine as the primary treatment of anaphylaxis. When food-related anaphylaxis occurs, patients should receive education regarding their food allergies, an epinephrine auto-injector, and follow-up with a food allergy specialist to reduce the risk of future food-related reactions.
Dietary intervention is a crucial component of food allergy management but can negatively impact nutrient intake. A comprehensive nutrition assessment with appropriate intervention is warranted in all children with food allergies to meet nutrient needs and optimize growth. Nutrition assessment may also be indicated in adults with food allergy. Frequently, an elimination diet is absolutely necessary to prevent potentially life-threatening anaphylaxis. Allergen elimination can also improve chronic symptoms, such as atopic dermatitis, when a food is proven to trigger symptoms. Allergen elimination goals are to prevent acute and chronic food-allergic reactions in the safest and least restrictive environment to supply a balanced diet that promotes health in children and adults.
Among grains and legumes, wheat and soybean are the most frequent and well-characterized allergenic foods. Wheat proteins are divided into water/salt-soluble and water/salt-insoluble (gluten) fractions. The most dominant allergen in the former is α-amylase/trypsin inhibitor, which acts as an inhaled allergen causing baker's asthma. Gluten allergens, including ω-5 gliadin and high- and low-molecular-weight glutenins, contribute to wheat-dependent exercise-induced anaphylaxis in adults and immediate-type wheat allergies, including anaphylaxis, in children. Recently, wheat allergies exclusively caused by hydrolyzed wheat proteins or deamidated glutens have been reported, and the presence of unique IgE-binding epitopes has been suggested. Soybean allergens contributing to immediate-type allergic reactions in children are present in seed storage proteins, namely Gly m 5, Gly m 6 and Gly m 8. However, pollen-related soybean allergy in adults is caused by the Bet v 1 homolog of soybeans, Gly m 4. Taken together, the varying clinical manifestations of wheat and soybean allergies are predominantly caused by their different allergen components.
While first accounts of food allergy date back to antiquity, only in recent years has food allergy become recognized as one of the major allergic diseases. During the last decade the output of research papers on food allergy increased tremendously, and today, issues related to food allergies still attract a lot of attention among academics and the general public. Featuring contributions by world-renowned experts, this book presents the current concept, practice and recent advances in the field of food allergy. A comprehensive background section provides a historical retrospective and information on the immunological basis and epidemiology of food allergies. Main topics discussed include clinical aspects, diagnosis and management, allergen-based food allergies, and disease-based food allergies. Furthermore, nutritional aspects and diets, public policy and educational programs are covered as well as recent hot topics such as molecular-based allergen diagnosis, eosinophilic gastrointestinal food allergies and oral immunotherapy. Allergists, pediatricians, internists, dermatologists and general practitioners will find this publication an essential source of information as it provides in-depth insights into food allergies from childhood to adulthood.
There is currently no well-established disease-modifying treatment for food allergy, so management relies upon strict avoidance of food allergen(s), implementation of risk minimisation strategies to avoid inadvertent exposure and allergic reactions, and prompt management of acute allergic reactions, should they occur. The pharmacological management of acute food-induced allergic reactions is dependent on the underlying pathophysiology of the allergic reaction and the severity of clinical symptoms and signs. Mild to moderate symptoms of an immunoglobulin E-mediated acute allergic reaction may be treated effectively with an oral anti-histamine. In patients exhibiting the clinical features of anaphylaxis, adrenaline is the only first-line therapy recommended by expert consensus. Adjunctive therapies, including anti-histamines, beta-agonists and glucocorticoids, may be used in the subsequent management of immunoglobulin E-mediated anaphylaxis. Here, we present the current recommendations for the pharmacological management of acute food-induced allergic reactions, together with a summary of the evidence supporting these recommendations.
Fruit and vegetable allergies are the most prevalent food allergies in adolescents and adults. The identification of the allergens involved and the elucidation of their intrinsic properties and cross-reactivity patterns has helped in the understanding of the mechanisms of sensitisation and how the allergen profiles determine the different phenotypes. The most frequent yet contrasting fruit and vegetable allergies are pollen-food syndrome (PFS) and lipid transfer protein (LTP) syndrome. In PFS, fruit and vegetable allergies result from a primary sensitisation to labile pollen allergens, such as Bet v 1 or profilin, and the resulting phenotype is mainly mild, consisting of local oropharyngeal reactions. In contrast, LTP syndrome results from a primary sensitisation to LTPs, which are stable plant food allergens, inducing frequent systemic reactions and even anaphylaxis. Although much less prevalent, severe fruit allergies may be associated with latex (latex-fruit syndrome). Molecular diagnosis is essential in guiding the management and risk assessment of these patients. Current management strategies comprise avoidance and rescue medication, including adrenaline, for severe LTP allergies. Specific immunotherapy with pollen is not indicated to treat pollen-food syndrome, but sublingual immunotherapy with LTPs seems to be a promising therapy for LTP syndrome.
Food allergy includes a number of diseases that present with adverse immunological reactions to foods and can be IgE-mediated, non-IgE-mediated, or a combination of both mechanisms. IgE-mediated food allergy involves immediate hypersensitivity through the action of mast cells, whereas non-IgE-mediated food allergy is most commonly cell-mediated. These food allergies are thought to occur as a result of a breakdown in oral tolerance and, more specifically, from an aberrant regulatory T-cell response. Ongoing studies of experimental treatments for food allergy strive to induce oral tolerance and to teach us more about the pathogenesis of food allergy.
Among foods causing allergic reactions in children, peanut (a legume) and tree nuts (ie, walnut, hazel nut, Brazil nut, pecan) have attracted considerable attention for several reasons. Allergies to these foods are common, frequently have an onset in the first few years of life, generally persist, and account for severe and potentially fatal allergic reactions. Furthermore, the ubiquity of these foods in the diet makes avoidance difficult and accidental ingestions, with reactions, common. This review discusses recent and emerging information on the prevalence, clinical characteristics, natural history, genetic basis, and current treatment of these allergies. In addition, recent advances in the molecular and immunologic characteristics of these allergens, and novel therapeutic options under investigation in animal models, are reviewed.
The majority of research on food allergy has been bio-medical in orientation, focusing on issues such as the molecular structure of allergens, or aimed at methods of diagnosis. In the last decade, there has been a growing interest in the development of questionnaires that measure the impact of food allergy on health-related quality of life (HRQL). These studies have provided insight into the everyday burden of living with food allergy and have suggested ways that HRQL can be improved. The EuroPrevall project (europrevall@bbsrc.ac.uk) has given great impetus to research in the area of HRQL. In addition to clinical research on the prevalence, mechanisms and causes of food allergy, research output in the area of psycho-social impact has included HRQL measures for all age groups and examination of the socio-economic impact of food allergy. In this chapter, we review the literature on the impact of food allergy on children, teens and their parents; the majority of this data was generated over the life of the EuroPrevall project. We then examine both quantitative and qualitative research findings to provide an in-depth picture of the impact of food allergy on the concerns and everyday lives of children, teens, adults and parents. Research on factors that are related to and impact HRQL is also discussed. There is a strong emphasis throughout the chapter on developmental considerations of food allergy, spanning from infants to adults. We conclude by discussing methodological issues in relation to the measurement of HRQL in relation to food allergy. We offer some recommendations for future research and practice on HRQL so that HRQL measures can reach their full potential in research, practice and policy, with the help of the findings in this review. Overall, the findings suggest that food allergy has a strong impact on HRQL in terms of social, dietary, and psychological factors. 'Rules' and restrictions ostensibly apply to food, but because food is such an integral part of everyday life, these restrictions extend far beyond 'mealtimes'. Therefore, social events are experienced differently and have a different meaning for those living with food allergy, giving rise to feelings of exclusion and difference when compared to those without allergy. Children, teens, and parents need to cope with normal developmental changes as well as with the food allergy, placing them under increased psycho-social stress and leading to adverse effects on HRQL and coping. To address and attempt to alleviate such stressors, both quantitative and qualitative research suggests that targeting uncertainty should be a major goal for health professionals working with children, teens and families with a food allergy. Remarkable similarities in response to food allergy across countries suggest that policies and programmes that address quality of life issues may be relevant to many different populations. An in-depth understanding of the relationship between a diagnosis of food allergy and HRQL, as well as the factors that impact it, will ultimately lead to the promotion of earlier, more effective preventive strategies and interventions that are focused on maximising optimal health development and quality of life.
Recent studies have suggested that the prevalence of food allergy is increasing in many parts of the world. However, many epidemiology studies have been based only on questionnaires without objective testing. The data from these studies do show that the pattern of food allergies is different across the world. In general, studies using objective testing reported a lower prevalence than those without objective testing. The most common food allergens are cow's milk, hen's egg, wheat, fish, shellfish, peanuts, and tree nuts. Recent evidence also suggested that some of these allergies might not persist longer than the childhood years. However, unlike milk and egg allergies, seafood allergy is more likely to persist into adulthood. Peanuts and tree nuts are some of the most common causes of anaphylaxis in developed countries, but these are rather rare in developing countries. Given the early evidence of an increasing prevalence of food allergies, continual monitoring of the changing prevalence and patterns in different countries should help us understand the true causes of food allergy.
Cow's milk allergy is among the more frequent food allergies in infants and children. Because its suspicion stems from a plethora of symptoms, it is frequently reported. However, the development of a rigorous diagnostic pathway will reduce the diagnosed children to less than 50% of those reported. Cow's milk allergy is the only specific food allergy for which an EBM guideline exists. According to the guidelines (Diagnosis and Rationale for Action against Cow's Milk Allergy), a diagnostic process based on the pre-test probability of this condition is available. Treatments include avoidance, the substitution of cow's milk with an appropriate formula, and in some cases, oral immunotherapy. Treatment choice is also guided by these guidelines.
Molecular allergology is a breakthrough science that enables the quantification of IgE antibodies against individual allergen protein components at the molecular level. The diagnosis of IgE-mediated allergic disorders is based on the clinical history and on sensitization demonstrated through an allergy test. Identifying whether the sensitization is primary (species specific) or due to cross-reactivity with proteins with similar protein structures helps the clinician to judge the risk of allergic reaction. This is possible today because allergen component tests for food allergy are now available for clinicians to use in everyday practice.
Despite a trend towards delayed weaning, food allergies (FAs) have increased in the past few decades and are now considered a public health concern, resulting in significant morbidity as well as occasional mortality. Whilst genetic factors are clearly important in the development of FA, a rise in FAs has occurred over a short period of time and is therefore unlikely to be due to germ-line genetic changes alone. Thus, it seems plausible that one or more environmental exposures may, via epigenetic changes, result in the interruption of the 'default immunologic state' of tolerance to foods. Strategies are therefore required for the prevention of FA: primary prevention seeks to prevent the onset of IgE-sensitisation; secondary prevention seeks to interrupt the development of FA in IgE-sensitised children; and tertiary prevention seeks to reduce the expression of 'end-organ' allergic disease in children with established FA. This chapter will outline the major findings in this field, with the aim of equipping the clinician with an evidence-based approach to a burgeoning yet poorly understood clinical problem. We also highlight the methodological challenges hindering the interpretation of existing FA studies. Fortunately, there are now robust studies underway, the results of which are expected to guide public health recommendations with respect to how and when to introduce major allergenic foods to children, regardless of allergic risk.
Gastrointestinal food allergies present during early childhood with a diverse range of symptoms. Cow's milk, soy and wheat are the three most common gastrointestinal food allergens. Several clinical syndromes have been described, including food protein-induced enteropathy, proctocolitis and enterocolitis. In contrast with immediate, IgE-mediated food allergies, the onset of gastrointestinal symptoms is delayed for at least 1-2 hours after ingestion in non-IgE-mediated allergic disorders. The pathophysiology of these non-IgE-mediated allergic disorders is poorly understood, and useful in vitro markers are lacking. The results of the skin prick test or measurement of the food-specific serum IgE level is generally negative, although low-positive results may occur. Diagnosis therefore relies on the recognition of a particular clinical phenotype as well as the demonstration of clear clinical improvement after food allergen elimination and the re-emergence of symptoms upon challenge. There is a significant clinical overlap between non-IgE-mediated food allergy and several common paediatric gastroenterological conditions, which may lead to diagnostic confusion. The treatment of gastrointestinal food allergies requires the strict elimination of offending food allergens until tolerance has developed. In breast-fed infants, a maternal elimination diet is often sufficient to control symptoms. In formula-fed infants, treatment usually involves the use an extensively hydrolysed or amino acid-based formula. Apart from the use of hypoallergenic formulae, the solid diets of these children also need to be kept free of specific food allergens, as clinically indicated. The nutritional progress of infants and young children should be carefully monitored, and they should undergo ongoing, regular food protein elimination reassessments by cautious food challenges to monitor for possible tolerance development.
In young children, food allergy is usually acquired via the gastrointestinal tract and directed toward egg and milk. Adolescent and adult patients, however, mainly acquire food allergy via primary sensitization to inhalant allergens on the basis of cross-reactivity between proteins in inhalant sources and in food. This type of food allergy is frequently mediated by sensitization to broadly represented allergens, or so-called panallergens. Food allergic reactions in adult patients - similar to those in children - range in severity from very mild and local symptoms, as in contact urticaria of the oral mucosa, to systemic symptoms involving distal organs, to a fatal outcome. Plant foods, such as fruits, nuts, and vegetables, are the most prevalent allergenic foods in this age group.
The currently known food allergens are assigned to a relatively small number of protein families. Food allergens grouped into protein families share common functional and structural features that can be attributed to the allergenic potency and potential cross-reactivity of certain proteins. Molecular data, in terms of structural information, biochemical characteristics and clinical relevance for each known allergen, including isoforms and variants, are mainly compiled into four open-access databases. Allergens are designated according to defined criteria by the World Health Organization and the International Union of Immunological Societies Allergen Nomenclature Sub-committee. Food allergies are caused by primary sensitisation to the disease-eliciting food allergens (class I food allergen), or they can be elicited as a consequence of a primary sensitisation to inhalant allergens and subsequent IgE cross-reaction to homologous proteins in food (class II food allergens). Class I and class II allergens display different clinical significance in children and adults and are characterised by different molecular features. In line with this, high stability when exposed to gastrointestinal digestion and heat treatment is attributed to many class I food allergens that frequently induce severe reactions. The stability of a food allergen is determined by its molecular characteristics and can be influenced by structural (chemical) modifications due to thermal processing. Moreover, the immunogenicity and allergenicity of food allergens further depends on specific T cell and B cell epitopes. Although the T cell epitope pattern can be highly diverse for individual patients, several immuno-prominent T cell epitopes have been identified. Such conserved T cell epitopes and IgE cross-reactive B cell epitopes contribute to cross-reactivity between food allergens of the same family and to clinical cross-reactivity, similar to the birch pollen-food syndrome.
Although awareness that food can cause adverse symptoms and even death in some individuals has been present since the times of Hippocrates, it was not until the seminal experiment of Prausnitz that the investigation of food allergy had 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. Until the studies of Charles May and colleagues in the mid- to late '70s, there was a great deal of skepticism in the medical world about the relevance of food allergy and how to diagnose it, since standard skin testing was known to correlate poorly with clinical symptoms. With the introduction of the double-blind, placebo-controlled oral food challenge by May, the study of food allergy has become evidence based, and tremendous strides have been made in the study of basic immunopathogenic mechanisms and natural history as well as in the diagnosis and management of food allergies. Today, various IgE- and non-IgE-mediated food allergic disorders have been well characterized, and efforts to reverse these allergies using various immunotherapeutic strategies are well under way.
Given its increasing prevalence and potential severity, food allergy not only negatively impacts the health and quality of life of affected individuals but also carries a significant economic burden. To address these problems, a community approach including efforts to increase awareness of food allergy among the general public and the implementation of appropriate public policies to keep affected individuals safe is required. This chapter reviews the general public's knowledge and perceptions of food allergy, the disease's psychosocial impact on affected individuals, and the current state and future directions of food allergy public policy.
Food allergy is a potentially life-threatening condition affecting almost 10% of children, with an increasing incidence in the last few decades. It is defined as an immune reaction to food, and its pathogenesis may be IgE mediated, mixed IgE and non-IgE mediated, or non-IgE mediated. Potentially all foods can cause food allergy, but a minority of foods are responsible for the vast majority of reactions reported. A good clinical history is crucial for an accurate diagnosis. Allergy tests, including the skin prick test and measurement of specific IgE antibodies, are useful tools in the case of IgE-mediated or mixed allergy but have not been shown to be of any help in delayed allergic reactions to foods.
