Update on hidden food allergens and food labeling.

This article is intended to review the current literature on "hidden" food allergens and the various ways in which sensitized individuals may be exposed to these allergens. A focus on advances in food labeling, and the Food Allergen Labeling and Consumer Protection Act (FALCPA) is also included, because it assists food-allergic consumers in the strict avoidance of specific foods. Article information was gathered primarily through a computer search of relevant data relating to human subjects. Our findings indicate that sensitized individuals can unknowingly be exposed to allergenic proteins in foods through cross-contact, food containing allergenic nonfood products, food additives, and cross-reactivity. Furthermore, food packaging and formulation errors, ingredient switching, and foods not covered under the FALCPA were also found to be sources of hidden food allergens. There are many ways in which hypersensitive individuals can be exposed to potentially dangerous allergens despite careful avoidance. Furthermore, health care providers should consider various sources of hidden allergens in food-allergic individuals with an unclear etiology. Food hypersensitivity has been identified as a significant medical dilemma in our society. Recent efforts to increase public awareness and strides made in labeling of food products are encouraging.     

Skin testing and food challenges for the evaluation of food allergy

Skin testing by prick technique has an excellent safety record in the evaluation of food hypersensitivity. Skin prick tests for the common food allergens are excellent tools for identifying those at very low risk of reaction on eating the food but are of variable value in identifying patients who will be positive on challenge. Intradermal skin tests to foods are less safe and appear to add no predictive information. Skin tests to less common food allergens, especially fruits, are less well characterized and may require use of the food item itself as the source of allergen rather than a commercial extract. For a few foods, the CAP system fluorescent enzyme immunoassay (Pharmacia, Peapack, NJ) recently has been shown to have good ability to identify patients at very high probability of reaction on oral challenge. Oral challenge remains the definitive method of demonstrating sensitivity or tolerance to a food. The double-blind, placebo-controlled food challenge is the gold standard of diagnosis, but in many situations, simpler open or single-blind challenge procedures may be substituted. With careful, incremental dosing and a low starting dose, oral challenges for food hypersensitivity have an excellent safety record. Skin prick tests are of little value in the evaluation of adverse food reactions not mediated by IgE. Oral challenge is relied upon in this situation for definitive diagnosis, but challenges may be cumbersome if the time course of the presumed reaction is not rapid.     

Management of Food Allergy in Japan “Food Allergy Management Guideline 2008 (Revision from 2005)” and “Guidelines for the Treatment of Allergic Diseases in Schools”

In 2005, the “Food Allergy Management Guideline 2005” was published. In order to encompass food allergy from infancy to adulthood, the project committee included not only pediatricians, but also internists, dermatologists, and otolaryngologists. After the release of the guideline, oral food challenge tests were approved as a medical examination on hospital admission by the national health insurance system in 2006, and the tests at outpatient clinics were also approved in 2008. As clearly stated in the guideline, it is essential for general practitioners to refer food allergy patients to specialists to receive accurate diagnosis. A specialist is needed because the oral food challenge test, which is sometimes required for accurate diagnosis, carries the potential risk of developing an adverse reaction. In 2008, the “Food Allergy Management Guideline 2008” was revised to update recent advances, such as the appropriate conditions needed to perform oral food challenge tests and probability curves for hen's egg and cow's milk developed in Japan. In the same year, “The Guidelines for the Treatment of Allergic Diseases in Schools” was published by the Japanese Society of School Health. In addition to the guideline, “School Life Management Certificate (for Allergic Diseases)” was developed in order to allow the verification of the diagnosis and encourage the discussion of countermeasures by parents/guardians and school teachers for students requiring special care. It is hoped that this review article will be useful for doctors treating food allergy and that the quality of life of food allergy patients and their parents will be improved.     

Food allergy: from diagnosis to treatment

Adverse food reactions, an adverse health effect arising from an immune or nonimmune response that occurs reproducibly on the exposure to a given food, can be divided into toxic and hypersensitivity reactions. When an immunologic mechanism has been shown, hypersensitivity food reactions should be referred to as food allergy that may be IgE- or non-IgE-mediated. Food allergy diagnosis is mainly guided by a correct and accurate history and physical examination, thus leading to prick test and elimination diets. The treatment gold standard is still represented by an elimination diet together with antihistamines and corticosteroid usage in order to reduce the gastrointestinal and potentially life-threatening systemic symptoms. Other treatments are currently under investigation with promising results.     

Immunotherapy for food allergy

Food allergy is an important cause of life-threatening hypersensitivity reactions. Avoidance of allergenic foods is the only method of prevention that currently is available for sensitized patients. This method of prevention is difficult and often impossible. With better characterization of allergens and better understanding of the immunologic mechanism, investigators have developed several therapeutic modalities that potentially are applicable to the treatment and prevention of food allergy. Therapeutic options currently under investigation include peptide immunotherapy, DNA immunization, immunization with immunostimulatory sequences, anti-IgE therapy, and genetic modification of foods. These exciting developments hold promise for the safe and effective treatment and prevention of food allergy in the next several years.     

The Likelihood of Remission of Food Allergy in Children: When Is the Optimal Time for Challenge?

Although diagnostic testing methods for food hypersensitivity have improved over time, both in vivo and in vitro methods are significantly flawed, especially as evidenced by the frequent occurrence of false-positive test results. Because of these limitations, oral food challenge testing remains an essential element in the diagnosis and management of food allergy. In fact, the double-blind, placebo-controlled food challenge remains the gold standard for the diagnosis of food allergy. In this review, we focus on the optimal timing of oral food challenges, especially for patients with a known food allergy, to determine if the food allergy may have been outgrown.     

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.     

Food allergy in gastroenterologic diseases： Review of literature

INTRODUCTION Food allergy is recognized as a common worldwide prob- lem, and, like other atopic disorders, its incidence seems to increase. Moreover, food-related allergic disorders are the leading cause of anaphylactic reactions treated in the emer- genc…     

Hidden fish substance triggers allergy.

Food allergy (hypersensitivity) is a form of adverse food reaction caused by an immunological response to a particular food. IgE-mediated food allergy is responsible for most immediate-type food-induced hypersensitivity reactions. The prevalence of food allergy in the general population, not including oral allergy syndrome, is about 1-2%. While adults might tend to be allergic to fish, crustaceans, peanuts, and tree nuts, children, on the other hand, tend to be allergic to cow's milk, egg white, wheat, and soy. Food is the most common eliciting factor of anaphylaxis (45%), followed by drugs (29%), and insect stings (21%). Our study describes a 3 1/2-year-old boy who is allergic to fish consumed via ingestion and inhalation. This case is a good example of how easily people with food allergies can unintentionally consume foods to which they allergic, and is a clear demonstration of the dangers of such effects.     

Food hypersensitivity reactions visualised by ultrasonography and magnetic resonance imaging in a patient lacking systemic food-specific IgE

BACKGROUND: Abdominal complaints related to food intake might be due to hypersensitivity. A firm diagnosis of food allergy is often difficult to establish, particularly in the absence of systemic food-specific IgE. Using ultrasonography and magnetic resonance imaging (MRI) we were able to visualise the intestinal response in one such case. METHODS: A 24-year-old female presented with self-reported food hypersensitivity, particularly related to the intake of egg. Nausea and diarrhoea were predominant symptoms. Double-blind placebo-controlled food challenge with raw egg was positive, but all other conventional tests of food hypersensitivity, including skin prick test, total and food-specific IgE in serum, were negative. A thorough investigation programme could not reveal any organic disease of the gastrointestinal tract. We extended the evaluation to include two new provocation tests, where intestinal wall thickening and the amount of luminal liquid were monitored by external abdominal ultrasound and MRI. RESULTS: Both ultrasound and MRI investigations indicated intestinal wall thickening and influx of large amounts of fluid into the proximal small intestines within 10 min of duodenal challenge with egg. The response was associated with abdominal pain and bloating. CONCLUSIONS: The response to provocation was typical of an immediate allergic reaction. Our results indicate that local food-induced hypersensitivity reactions can occur in the gut in the absence of systemic indications of IgE-mediated allergy. Abdominal ultrasonography and MRI might become valuable tools for documenting such responses.     

Detection of local mast-cell activity in patients with food hypersensitivity.

BACKGROUND: Mast cells play a central role in many inflammatory diseases and assessment of their activation may be of use to provide objective confirmation of the outcome of food challenge in the diagnosis of food hypersensitivity. However, to date, assessment of mast-cell activation using serum markers has been unsuccessful. OBJECTIVE: The aim of this study was to explore whether locally released tryptase could be detected in stool samples from patients with food hypersensitivity. METHODS: Nine patients (median age, 55 years; range, 26 - 68 years) with food hypersensitivity confirmed by double-blind placebo-controlled food challenge were included in the study. Tryptase concentration was assessed in stool samples collected before and after an open food challenge at home and symptoms were recorded throughout the study. Tryptase concentration was also assessed in stool samples from 16 apparently healthy individuals (median age, 44 years; range, 27 - 72 years). RESULTS: Measurement of fecal tryptase levels in 16 healthy control subjects revealed an upper limit of the normal range (mean + 2 SD of log transformed data) of 10 ng/g. Fecal tryptase levels exceeded 10 ng/g in 7 out of 9 patients in one or more samples obtained during the study. The tryptase levels varied between patients in response to the food challenge and the individual mean levels of tryptase correlated with the corresponding levels of the inflammatory marker eosinophil protein X (rho = 0.7500, P = .02). CONCLUSION: Measurement of tryptase levels in stool samples is feasible using the method described here. Our results revealed elevated concentrations of fecal tryptase in patients with food hypersensitivity. However, several factors, including food exposure, may account for the increase in fecal tryptase and further studies are necessary to elucidate the role of mast cells in food hypersensitivity.     

Patients with subjective food hypersensitivity: the value of analyzing intestinal permeability and inflammation markers in gut lavage fluid

BACKGROUND/AIM: Subjective food hypersensitivity is prevalent in the general population. The aim of this study was to seek objective evidence of food hypersensitivity by analyzing intestinal permeability and inflammation markers in gut lavage fluid. METHODS: Fifty-two patients with abdominal complaints self-attributed to food hypersensitivity were examined by skin prick test, serum IgE analysis, double-blind, placebo-controlled food challenge (DBPCFC), and intestinal lavage. The results were compared with those of 44 patients without food hypersensitivity. Neither the patients nor the controls had organic diseases that could explain their symptoms. Intestinal lavage was performed by administering 2 liters of isotonic polyethylene glycol (molecular weight 3,350 daltons) solution containing 50 microCi of [51Cr]EDTA through a nasoduodenal tube. The first clear fluid passed per rectum was collected and analyzed for histamine, eosinophilic cationic protein (ECP), tryptase, and calprotectin. The intestinal permeability was assessed by determining the 5-hour urinary excretion of [51Cr]EDTA. Calprotectin was also analyzed in native faecal samples. RESULTS: The ECP concentration in gut lavage fluid was significantly higher in the patients than in the controls (p = 0.007), but the overlap between groups was large. Food hypersensitivity was confirmed by positive DBPCFC in only 4 patients. On average, histamine and ECP concentrations were high in these patients. Tryptase, intestinal permeability, and faecal and lavage calprotectin levels were normal. CONCLUSIONS: Very few patients had objective evidence of food hypersensitivity. Analyzing intestinal permeability and inflammation markers in gut lavage fluid did not contribute to the diagnosis, but further studies on histamine and ECP are warranted.     

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.     

Can food protein induced enterocolitis syndrome shift to immediate gastrointestinal hypersensitivity? A report of two cases

Food protein induced enterocolitis syndrome (FPIES) is a food-related non-IgE-mediated gastrointestinal hypersensitivity disorder. Atypical FPIES is characterized by the presence of specific IgE for the causative food. The guidelines suggested for diagnostic oral food challenge in pediatric patients affected by suspected FPIES are different from the ones for children with IgE-mediated food allergy. We describe two cases of atypical FPIES that turned into IgE-mediated gastrointestinal anaphylaxis. Our experience suggests to adapt OFC according to the outcome of specific IgE for the causative food When causative food-related IgE werepositive, we suggest to follow the guidelines for IgE mediated food allergy.     

Food-protein-induced enterocolitis syndrome caused by fish

IntroductionFood protein-induced enterocolitis syndrome (FPIES) occurs in infants. Typical symptoms include profuse vomiting and/or diarrhea several hours after ingestion of a given food. The disorder is a non-IgE mediated food hypersensitivity. The most frequently involved foods are milk and soy, but some cases of FPIES induced by solid foods have been described. We report 14 patients with FPIES due to fish protein.Material and methodsHistory and physical examination, skin prick test (SPT) with fish allergens and Anisakis simplex, prick-by-prick test with implicated fish and determination of specific IgE antibodies against fish were performed. In eight children atopy patch test (APT) were also performed. In nine patients an open oral food challenge with the implicated fish was carried out.ResultsThere were six boys and eight girls, aged from 9 to 12 months at diagnosis, with between two and six reactions to the offending fish proteins before the diagnosis was established. Four patients had a previous history of atopy. Presenting symptoms included diarrhea in two patients, profuse vomiting in six patients, and recurrent vomiting and subsequent diarrhea in three patients. In addition to these symptoms, associated septic appearance, apathy and lethargy were present in the remaining three patients. Onset of symptoms occurred a few minutes after fish ingestion in two patients and from 60 minutes to 6 hours in the 12 remaining patients. SPT to fish were negative in all patients. Serum food-specific IgE antibodies were negative in all patients except one. APT was positive in three patients. Open oral challenge (OC) was performed in nine infants and was positive in all. The patients were followed-up for between 1 and 7 years after diagnosis, and follow-up OC tests were performed after fish had been eliminated from the patients’ diet for 3-4 years. Four patients became clinically tolerant to the causal food. Three patients currently tolerate only one type of fish (swordfish).ConclusionsWe report 14 patients with FPIES caused by fish protein. The symptoms suggest a form of cell-mediated, non-IgE mediated food hypersensitivity. The gold standard for diagnosis is OC, although caution should be exercised in infants with several reactions or a recent diagnosis. After a period of elimination of the causal food from the diet, tolerance can develop.     

Diagnosis of Food Allergy: Epicutaneous Skin Tests, In Vitro Tests, and Oral Food Challenge

Food allergy is becoming an increasingly common diagnosis. Because of this increase in prevalence, it is imperative that physicians evaluating patients with possible adverse reactions to foods understand the currently available assays and how they should best be used to accurately diagnose the disease. Simple tests such as skin prick testing (SPT) and serum food-specific IgE testing are the most commonly used diagnostic tests to evaluate for IgE-mediated food reactions. However, these tests, which measure sensitization and not clinical allergy, are not without pitfalls, and their utility must be appreciated to avoid over- and underdiagnosis. Although the physician-supervised oral food challenge remains the gold standard for food allergy diagnosis, a careful medical history paired with SPT and serum food-specific IgE testing often can provide a reliable diagnosis. In this review, we examine the usefulness and pitfalls of SPT and serum food-specific IgE levels, as well as examine atopy patch testing and other emerging tests, such as component-resolved diagnostics and the basophil activation test. Finally, we describe the use of the double-blind, placebo-controlled oral food challenge as the current gold standard for food allergy diagnosis.     

Quoi de neuf en allergologie pédiatrique en 2004 ? Partie 3 : allergie cutanée,alimentaire, médicamenteuse et aux venins d'insectes (Une revue de la littérature internationale d'octobre 2003 à septembre 2004)

Severity and risk of persistence/relapse of atopic dermatitis are correlated with total IgE levels and food sensitization. Weaning to hypoallergenic formula improves SCORAD and gut barrier function in breastfed infants with persistent atopic dermatitis. Risk of anaphylaxis is high in children with cold-induced urticaria, and these children should be provided with an epinephrine autoinjector. Occult sensitizations are important risk factors for food allergy. The predictive values of serum egg-specific IgE levels are debated. The diagnostic value of atopy patch-tests with foods is confirmed in children with non-immediate food hypersensitivity reactions. Risk of persistence of food allergy is high in children with high specific IgE levels and/or with a low rate of decrease in food-specific IgE levels. Oral desensitization induces tolerance in children with persistent cow's milk allergy, except for children with very high levels of specific IgE. However, tolerance to anaphylactogenic food may be temporary, with the occurence of severe relapses after a few months. Ten per cent of children treated with penicillins are sensitized to these antibiotics. However, only a few of these children are at risk of developing allergy to penicillins. Non allergic hypersensitivity to non steroidal anti-inflammatory drugs is frequent in children. Sublingual immunotherapy may be efficient in children with latex hypersensitivity. A clinically important number of non-hyposensitized children do not outgrow hymenoptera venom allergy. In contrast, venom immunotherapy leads to a significantly lower risk of systemic reaction to stings. Thus, children with moderate to severe allergic reactions to hymenoptera stings should receive specific immunotherapy.     

Oral rush desensitization with tomato: a case report.

Adverse food reaction in which no immunological mechanism is demonstrated should be termed nonallergic food hypersensitivity or food intolerance. We present the case of a 12-year-old girl with a clinical history of abdominal pain, nausea, and general malaise after tomato intake which completely remitted with antihistamines. The patient underwent a complete allergy evaluation: skin prick tests, serum specific IgE and IgG4 tests to tomato, and double-blind placebo-controlled food challenge. Skin prick tests and specific IgE to tomato were negative while the food challenge was positive. At the end of the workup, the patient underwent an oral rush desensitizing treatment. At the end of the treatment the patient could eat a maintenance dose of 100 g of tomato daily with no side effects at all. This successful result suggests that the oral desensitizing treatment can be used in patients with nonallergic food hypersensitivity.     

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 Intolerances and Eosinophilic Esophagitis in Childhood

Food intolerance is an adverse reaction to a particular food or ingredient that may or may not be related to the immune system. A deficiency in digestive enzymes can also cause some types of food intolerances like lactose and gluten intolerance. Food intolerances may cause unpleasant symptoms, including nausea, bloating, abdominal pain, and diarrhea, which usually begin about half an hour after eating or drinking the food in question, but sometimes symptoms may delayed up to 48 h. There is also a strong genetic pattern to food intolerances. Intolerance reactions to food chemicals are mostly dose-related, but also some people are more sensitive than others. Diagnosis can include elimination and challenge testing. Food intolerance can be managed simply by avoiding the particular food from entering the diet. Babies or younger children with lactose intolerance can be given soy milk or hypoallergenic milk formula instead of cow’s milk. Adults may be able to tolerate small amounts of troublesome foods, so may need to experiment. Eosinophilic esophagitis (EE) is defined as isolated eosinophilic infiltration in patients with reflux-like symptoms and normal pH studies and whose symptoms are refractory to acid-inhibition therapy. Food allergy, abnormal immunologic response, and autoimmune mechanisms are suggested as possible etiological factors for EE. This article is intended to review the current literature and to present a practical approach for managing food intolerances and EE in childhood.