Food Allergy: Our Evolving Understanding of Its Pathogenesis,Prevention, and Treatment

Food allergy is defined as an IgE-mediated hypersensitivity response to ingested food with allergic symptoms ranging from urticaria to life-threatening anaphylaxis. Food allergy is thought to develop because of (1) failed induction of tolerance upon initial exposure to food antigen or (2) breakdown of established tolerance to food antigen. We review current understanding of the pathogenesis, epidemiology, and natural history of food allergy, including the unconventional IgE-mediated food allergy to mammalian meat known as alpha-gal food allergy. We highlight emerging data on food allergy treatment and prevention, emphasizing the growing appeal of manipulating the gut microenvironment using probiotics and helminth products to blunt systemic allergic responses to food.     

IgE-mediated food allergy--extensive review of the literature

Adverse reactions to food, i.e. food allergy and intolerance have gained considerable attention. This overview focuses on the diagnosis and management of IgE-mediated food allergy that is believed to be responsible for most immediate-type food-induced hypersensitivity reactions. Clinically, these reactions are characterised by a variety of signs and symptoms that occur within minutes or hours after consumption of the offending food. Reactions may be limited or more generalised with involvement of the skin, nose, eyes, and/or lungs. In more severe cases, cardiovascular symptoms including hypotension, shock, cardiac dysrhythmias and death can occur. In food-allergic individuals, IgE is produced against naturally occurring food components, primarily glycoproteins that usually retain their allergenicity after heating and/or proteolysis. While adults tend to be allergic to fish, crustaceans, peanuts and tree nuts, children tend to be allergic to cow's milk, egg white, wheat and soy more frequently. "Emerging" food allergens include tropical fruits, sesame seeds, psyllium, spices and condiments. These allergies frequently represent a cross-allergy to an allergen derived from another source, e.g. pollens or natural rubber latex. The evaluation of IgE-mediated food allergy relies on a careful history, physical examination, appropriate skin testing or in vitro testing with food extracts, and/or double blind, placebo-controlled food challenges. Avoidance remains the mainstay of therapy. However, allergens may be "hidden" and labelling can be non-precise or misleading, thereby severely hampering prevention. Patients with severe allergies should keep at hand an emergency kit with adrenaline, an antihistamine and an injectable rapid onset-of-action corticosteroid. At present there is no evidence to support the use of immunotherapy, except for research purposes. Production of "hypoallergenic" food is hampered by incomplete methods for assessing the allergenic potential of such novel foods.     

Food allergy in Catalonia: Clinical manifestations and its association with airborne allergens

BackgroundFood allergy affects around 6% of the European population and its prevalence worldwide has been increasing in the last decades, but studies focused on investigating food allergy epidemiology in Europe are lacking.ObjectiveThe Cibus project was created to register the main culprit foods and their clinical manifestations in food allergic patients in Catalonia.MethodsA specific online database was designed. Allergists from eight different Catalan hospitals registered the new diagnoses of food allergy.Results618 food allergic patients were included. Egg and milk were the main elicitors in the early ages, while fruits and nuts were the most frequent in patients >14 years old. Fish was more frequent in children, while seafood and Anisakis allergy were more frequent in the >14-year-old group. Overall, peach was the most prevalent food eliciting an allergic reaction (10%). Food allergy diagnosis was reached using compatible clinical history and positive skin prick test to the involved food in 98% of cases. Globally, urticaria was the most frequently reported manifestation in our population (48.2%), followed by oral allergy syndrome (25.6%) and anaphylaxis (24.8%).ConclusionsThe Cibus project gives a full overview of the profile of food allergic patients in Catalonia and reinforces the predominance of plant food allergies in the Mediterranean area.     

Characterisation of immune mediator release during the immediate response to segmental mucosal challenge in the jejunum of patients with food allergy

BACKGROUND: Food allergy is a common complaint among patients with a broad spectrum of abdominal and extra-abdominal symptoms that must be distinguished from other more common non-immunological food intolerances. AIMS: To investigate whether human intestinal hypersensitivity reactions are associated with detectable release of inflammatory mediators from activated cells, which may serve as a biological marker of true allergic reactions. PATIENTS/METHODS: In eight patients with food allergy and seven healthy volunteers, a closed-segment perfusion technique was used to investigate the effects of jejunal food challenge on luminal release of tryptase, histamine, prostaglandin D(2), eosinophil cationic protein, peroxidase activity, and water flux. RESULTS: Intraluminal administration of food antigens induced a rapid increase in intestinal release of tryptase, histamine, prostaglandin D(2), and peroxidase activity (p<0.05 v basal period) but not eosinophil cationic protein. The increased release of these mediators was associated with a notable water secretory response. CONCLUSIONS: These results suggest that human intestinal hypersensitivity reactions are characterised by prompt activation of mast cells and other immune cells, with notable and immediate secretion of water and inflammatory mediators into the intestinal lumen. Analysis of the profile of markers released into the jejunum after food provocation may be useful for the objective diagnosis of food allergy.     

Prevalence of food allergy in 137 latex-allergic patients.

There have been reports of increased prevalence of certain food allergies in patients with Type I latex allergy (LA). A detailed food allergy history was obtained from 137 patients with LA. Latex allergy was defined by positive history of IgE mediated reactions to contact with latex and positive skin prick test to latex and/or positive in vitro test (AlaSTAT and/or Pharmacia CAP). Food allergy was diagnosed by a convincing history of possible IgE mediated symptoms occurring within 60 minutes of ingestion. We identified 49 potential allergic reactions to foods in 29 (21.1%) patients. Foods responsible for these reactions include banana 9 (18.3%), avocado 8 (16.3%), shellfish 6 (12.2%), fish 4 (8.1%), kiwi 6 (12.2%), tomato 3 (6.1%), watermelon, peach, carrot 2 (4.1%) each, and apple, chestnut, cherry, coconut, apricot, strawberry, loquat, one (2.0%) each. Reactions to foods included local mouth irritation, angioedema, urticaria, asthma, nausea, vomiting, diarrhea, rhinitis, or anaphylaxis. Our study confirms the earlier reports of increased prevalence of food allergies in patients with LA. We also report increased prevalence of shellfish and fish allergy not previously reported. The nature of cross reacting epitopes or independent sensitization between latex and these foods is not clear.     

The problems of the child with food allergies

In France, about 20% of schoolchildren are suffering from allergic diseases. Food allergy (FA) is steadily increasing for the last 20 years. Actually, 400,000 children are suffering from FA. Prevalence has increased this last decade. Frequency is estimated about 10% and increased twofold within 5 years. In France, the most common food allergens are: hen's egg (35%), peanut (24%), cow's milk (8%), mustard (6%), and fish (4%). Other food allergens as hazelnut, kiwi, wheat, sesame, seafood, and lupin. Cross reactivities to exist between fruits, vegetables pollen, latex and are more and more frequent. Multiple food allergies have recently been described.     

Hypersensitivity to Anisakis simplex: apropos of 36 cases

The authors report a group of 36 cases of hypersensitivity to Anisakis simplex, a fish parasite. They examined 11 boys and 25 girls who attended the Allergy service of the Central Hospital Marques of Valdecilla in Santander (Spain), between 12th May 1997 and 26th June 1998, for history of acute urticaria, most often after an aggravation of an allergic pathology. All were given an immunological examination that was composed of: food investigation, prick test, measurement of total and specific IgE and blood eosinophilia. In conclusion, the authors emphasize an increase in hypersensitivity to Anisakis simplex, masked by a food allergy and in spite of a nematode infection. Blood eosinophilia was normal in most cases.     

Asthma Symptoms and Bronchial Reactivity in School Children Sensitized to Food Allergens in Infancy

Food allergy in infancy usually disappears but is followed primarily by respiratory allergy. We hypothesized that children allergic to common food allergens in infancy are at increased risk of wheezing illness and bronchial hyperresponsiveness during school age. In a case-control study 69 children 7.2 to 13.3 years of age allergic to egg (N = 60) and/or fish (N = 29) in early life (first 3 years) who attended our allergy outpatient clinic were recruited. They received follow-up for 1 year and were evaluated by parental questionnaire, skin prick testing, spirometry, and metacholine bronchial challenge. Another 154 children (70 sensitized to inhaled allergens) recruited selectively from a general population sample with no history of food allergy during their first 3 years served as control subjects. Twenty-three children (38.3%) maintained their sensitization to egg and 19 (65.5%) to fish; the prevalence of sensitization to ≥ 1 inhaled allergen(s) increased from 59.4% to 71% during childhood. Current asthma symptoms were reported more frequently in the study group than in either control groups, sensitized to inhaled allergens and non-sensitized. Children of the study group showed a significantly increased frequency of positive response to metacholine bronchial challenge compared to the control group as a whole; the difference was statistically indicative when study groups separately were compared to the sensitized control subjects. Multivariate logistic regression analysis showed that bronchial hyperresponsiveness, as well as reported current asthma symptoms were associated with early wheezing and early sensitization to inhaled allergens but not with atopic dermatitis in infancy or persistence of egg or fish allergy. Children allergic to egg or fish in infancy are at increased risk for wheezing illness and hyperactive airways in school age; asthma and bronchial hyperresponsiveness development is mostly determined by wheezing and senzitization to inhaled allergens in early life regardless of atopic dermatitis in infancy or retention of food allergy.     

Study of food allergy in the Spanish population

BackgroundThe aim of the study was to investigate the prevalence of food allergy in patients referred to our Allergy Unit and to evaluate the diagnostic methods used.MethodsWe selected 674 patients referred to the Allergy Unit of our hospital from May 2002 to October 2004. The prevalence of symptoms was determined by a standardized questionnaire, prick-prick test, and serum specific IgE. In a second phase, double- blind oral challenge tests were administered.ResultsFood allergy was found in 106 patients (15.7%): 71 adults (67 %) and 35 children (33 %). The prevalence of food allergen sensitization was 14 % in adults and 20.8 % in children. A total of 89.6 % of the patients experienced symptoms immediately. Only 29.2% the patients of sought medical attention and adrenaline was administered to five (16.1 %). The foods most frequently involved in allergic reactions were fruits (56.6%) and tree nuts (22.6%).The most common symptoms were oral allergy syndrome (46.2 %), urticaria (32.1 %), and anaphylaxis (14.2 %).Combining the results of the questionnaire with those of prick-prick tests in patients whose allergy was confirmed by double-blind, placebo-controlled food challenge (9.1 %) showed a sensitivity of 95.5 %, a negative predictive value of 96 %, a specificity of 75 % and a positive predictive value of 73%.Conclusions1. The prevalence of food allergy in our sample was 9.1 %. 2. The foods most frequently involved in allergic reactions were fruits and tree nuts. 3. The most common symptoms were oral allergy syndrome, urticaria, and anaphylaxis. 4. Combining our questionnaire with in vivo tests allowed us to diagnose 75-96% of patients with no food allergy and 95 % of food allergy patients.     

Gastrointestinal food hypersensitivity: Symptoms, diagnosis and provocation tests.

As many as 25% of the general population in Western countries believe that they suffer from adverse reactions to food. However, the actual prevalence of food allergy is much lower. Food-induced allergic reactions cause a variety of symptoms including cutaneous, gastrointestinal and respiratory tract. Food allergy might be caused by IgE-mediated, mixed (IgE and/or non-IgE) or non-IgE-mediated (cellular) mechanisms. The clinical diagnosis is based on a careful history, laboratory findings (total and specific IgE), skin prick test, elimination diet and food challenges. New intestinal provocation tests have also been applied to pick up the allergic response of the duodenal mucosa by endosonography and external ultrasound. The management of food allergy continues to be a strict avoidance of the offending food item.     

The role of regulatory T cells in the acquisition of tolerance to food allergens in children

Food allergy is a pathological immune reaction that identifies certain harmless food proteins, usually tolerated by the majority of the people, as a threat. The prevalence of these food allergies is increasing worldwide and currently affects 8% of children. Exacerbated reactions to milk, egg and peanut are the most frequent in the pediatric population. It is well known that allergic diseases are a type 2 T-helper (Th2) immune response, characterized by the elevated production of IgE antibodies. However, little is known about the immune mechanisms responsible for the development of clinical tolerance toward food allergens. Recent studies have suggested the key role of regulatory T cells (Tregs) in controlling allergic inflammation. In this review, we discuss the importance of Tregs in the pathogenesis of food allergy and the acquisition of oral tolerance in children. Further investigation in this area will be crucial for the identification of predictive markers and the development of new therapies, which will represent a clinical and social benefit for these allergic diseases.     

Asthma and food allergy

PURPOSE OF REVIEW: Food allergy associated clinical and social burdens have increased substantially in prevalence in the past decade. Coexisting asthma is a significant problem as food reactions tend to be more severe when they involve the lung. Food allergy also increases asthma morbidity in adults and children. RECENT FINDINGS: Especially in early infancy, food allergy can be related to the development of future asthma. For diagnosis, cut-off values are very important for both specific IgE levels and skin-prick test when interpreting food allergy. For the treatment, oral immunotherapy is showing promise for refractory patients with IgE-mediated food allergies. SUMMARY: Food allergies can be classified as IgE-mediated or non-IgE-mediated. Besides foods, some additives and preservatives can also trigger asthma in certain people. Asthma may develop in about 5% of individuals who suffer from food allergy and current asthma may be triggered by foods among 6-8% of children and 2% of adults. Because of the difficulty of confirming diagnosis of food allergy, novel approaches are currently being investigated and new therapy modalities are being sought. For total asthma control and for better quality of life, steps should be taken to avoid foods in cases of food allergy.     

Japanese Guideline for Food Allergy

Food allergy is defined as “a phenomenon in which adverse reactions (symptoms in skin, mucosal, digestive, respiratory systems, and anaphylactic reactions) are caused in living body through immunological mechanisms after intake of causative food.”Various symptoms of food allergy occur in many organs. Food allergy falls into four general clinical types; 1) neonatal and infantile gastrointestinal allergy, 2) infantile atopic dermatitis associated with food allergy, 3) immediate symptoms (urticaria, anaphylaxis, etc.), and 4) food-dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate-type food allergy).Therapy for food allergy includes treatments of and prophylactic measures against hypersensitivity like anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be conducted only if they are inevitable because they places a burden on patients. For this purpose, it is highly important that causative foods are accurately identified. Many means to determine the causative foods are available, including history taking, skin prick test, antigen specific IgE antibodies in blood, basophil histamine release test, elimination diet test, oral food challenge test, etc. Of these, the oral food challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions such as anaphylaxis.     

Food Allergy and Quality of Life: What Have We Learned?

Health-related quality of life (HRQL) has become an emerging focus of interest in food allergy. Food allergy is a disease characterized by low mortality and symptoms which only occur during an allergic reaction. However, food-allergic patients continuously need to be alert when eating in order to prevent potentially severe allergic reactions, which may be fatal. Fear of such reactions and the need to be continuously vigilant may seriously compromise their HRQL. During the last decade, numerous studies have been published on food allergy and HRQL. The development of reliable, valid and responsive instruments for measuring HRQL in food allergic patients has facilitated this research even further. Such instruments have given insight into the specific problems a patient may face and the impact of food allergy-related interventions from the patient’s perspective. This paper focuses on the most significant findings regarding this topic since its first appearance in the literature in 2000.     

Diagnosis of Food Allergy Based on Oral Food Challenge Test

Diagnosis of food allergy should be based on the observation of allergic symptoms after intake of the suspected food. The oral food challenge test (OFC) is the most reliable clinical procedure for diagnosing food allergy. The OFC is also applied for the diagnosis of tolerance of food allergy. The Japanese Society of Pediatric Allergy and Clinical Immunology issued the 'Japanese Pediatric Guideline for Oral Food Challenge Test in Food Allergy 2009' in April 2009, to provide information on a safe and standardized method for administering the OFC. This review focuses on the clinical applications and procedure for the OFC, based on the Japanese OFC guideline.     

Allergies alimentaires précoces du nourrisson de 6 à 18 mois : étude de 69 cas

We report our findings on a group of 69 children without cow’s milk allergy who had one or several other food allergies between 6 and 18 months of age. Their initial symptoms were of moderate to severe intensity: 61 (88.5%) of them had had systemic symptoms, including angioedema (52%), generalized urticaria (36%), laryngeal edema (13%) and asthma (10%). In 11.5% of the patients, the first sign was severe acute eczema that did not respond to the usual treatment. The most important allergens, those identified with skin tests, serological assay for specific IgE antibody and labial or oral challenge tests, were egg (60.2%), peanut (50%), fish (10.3%) and cashew nut (5.8%). An atopic background was present in 90% of these infants. Of those allergic to eggs, 53% subsequently had no reaction to this food, whereas only one child allergic to peanuts and none of those allergic to cashew nuts or fish became symptom-free. Forty-three percent of the infants suffered from multiple food allergies, and asthma had developed in 33 (48%) of them. In conclusion, the early onset of food allergy and the presence of multiple sensitivities in this group of patients pointed to the seriousness and the unfavorable evolution of their allergic condition.     

Japanese Guideline for Food Allergy 2014

A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food."Various symptoms of food allergy occur in many organs. Food allergies are classified roughly into 4 clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type food allergy (urticaria, anaphylaxis, etc.), and (4) food dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate food allergy).The therapy for food allergies includes treatment of and prophylactic measures against hypersensitivity such as anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be used only if necessary because of the patient-related burden. For this purpose, it is very important that causative foods be accurately identified. There are a number of means available to identify causative foods, including the history taking, a skin prick test, detection of antigen-specific IgE antibodies in the blood, the basophil histamine release test, the elimination diet test, and the oral challenge test, etc. Of these, the oral challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions, such as anaphylaxis.     

Food allergy as a risk factor for asthma morbidity in adults.

BACKGROUND: The objective of this study was to evaluate the relationship between food allergy and asthma morbidity in adults. METHODS: We interviewed a cohort of persistent asthmatics from an inner-city clinic. Allergies to food were assessed by patient report of convincing symptoms of acute allergic reactions. Outcome variables included health resource utilization and medication use. RESULTS: The prevalence of allergy to fish, peanut, tree-nut, shellfish, and seed allergies were 3%, 3%, 3%, 13%, and 1%. Patients with allergies to > 1 food had increased asthma hospitalizations, ED visits, and use of oral steroids (p < 0.05 for all comparisons). Specifically, allergy to fish was associated with a greater risk of health resource utilization and increased frequency of oral steroid use (p < or = 0.03 for all comparisons). CONCLUSIONS: Self-reported allergy to foods was associated with worse outcomes, suggesting that food allergy may be a risk factor for increased asthma morbidity in adults.     

Food hypersensitivity in patients with seasonal rhinitis in Ankara

BackgroundFood hypersensitivity (FH) affects 1-2% of the adult population and is more common in atopic individuals. The aim of this study was to determine the frequency of FH and risk factors for its development in patients with seasonal rhinitis (SR) in our allergy clinic.MethodsWe performed a retrospective study based on the medical records of 774 patients out of 955 patients diagnosed with SR in an adult allergy clinic between 1 January 1991 and 31 December 2003.ResultsThe mean age of the patients was 29.1 ± 9.29 and 62.7 % were females. The most common major complaints were due to nasal symptoms in 82.3 %. The mean duration of SR was 6.8 ± 6.8 years. Patients were symptomatic for a mean of 3.5 ± 1.7 months per year. Skin prick tests (SPT) with common aeroallergens were positive in 685 patients (90.3 %), and the most common sensitivity was against timothy (85.1 %). The most common accompanying allergic disease was FH in 14%. FH according to history and the results of SPT performed with food allergens were discordant. The most common clinical manifestations of FH were oral allergy (49.1 %) and cutaneous symptoms (38.9 %). Risk factors for the development of FH in patients with SR were dermatological symptoms, rhinitis duration > 5 years, symptom duration > 3 months per year, SPT reactivity to Artemisia vulgaris, tree pollen allergens (Corylus avellena, Betula verrucosa), and bee allergy.ConclusionFH was the most common (14 %) accompanying allergic disease in patients with SR. SPT with food allergens have limited diagnostic value for food allergy and/or intolerance. Risk factors for developing FH in patients with SR in Turkey were dermatological symptoms, duration of rhinitis > 5 years, duration of rhinitis symptoms > 3 months per year, and SPT reactivity to Corylus avellena.     

Food specific oral immunotherapy: a potential treatment for food allergy

Food allergy is a potentially life-threatening condition affecting up to 8% of children and up to 2% of adults in westernized countries. There are currently no approved treatments for food allergy apart from avoidance. The apparent increase in incidence of food allergies over the past few decades calls attention to the need for effective, disease-modifying therapies for food allergies. Oral immunotherapy (OIT) is a promising experimental treatment in which food allergic patients consume increasing quantities of food in attempt to increase their threshold for allergic reaction. Studies are ongoing to determine whether OIT is capable of safely inducing not only desensitization but also tolerance to the allergenic foods. This article focuses on recent relevant studies of OIT for the treatment of common food allergies.