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…     

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.     

Pearls and Pitfalls in Diagnosing IgE-Mediated Food Allergy

The term “food allergy” is used by many patients and clinicians to describe a range of symptoms that occur after ingestion of specific foods. However, not all symptoms occurring after food exposure are due to an allergic, or immunologic, response. It is important to properly evaluate and diagnose immunoglobulin E (IgE)-mediated food allergy as this results in reproducible, immediate onset, allergic reactions that can progress toward life-threatening anaphylaxis. Proper diagnosis requires understanding of the common foods that cause these reactions in addition to key historical elements such as symptoms, timing and duration of reaction, and risk factors that may predispose to development of IgE-mediated food allergy. Diagnostic testing for food-specific IgE can greatly aid the diagnosis. However, false-positive test results are very common and can lead to overinterpretation, misdiagnosis, and unnecessary dietary elimination. This review discusses important aspects to consider during evaluation of a patient for suspected IgE-mediated food allergy.     

Allergen Component Testing for Food Allergy: Ready for Prime Time?

Food allergies can cause life-threatening reactions and greatly influence quality of life. Accurate diagnosis of food allergies is important to avoid serious allergic reactions and prevent unnecessary dietary restrictions, but can be difficult. Skin prick testing (SPT) and serum food-specific IgE (sIgE) levels are extremely sensitive testing options, but positive test results to tolerated foods are not uncommon. Allergen component-resolved diagnostics (CRD) have the potential to provide a more accurate assessment in diagnosing food allergies. Recently, a number of studies have demonstrated that CRD may improve the specificity of allergy testing to a variety of foods including peanut, milk, and egg. While it may be a helpful adjunct to current diagnostic testing, CRD is not ready to replace existing methods of allergy testing, as it not as sensitive, is not widely available, and evaluations of component testing for a number of major food allergens are lacking.     

Oral Food Challenges in Children: Review and Future Perspectives

Food allergy is a lifelong condition with no known treatment or cure. Allergy tests such as skin tests and blood tests are not always accurate when positive and are not necessarily diagnostic of a food allergy. A food allergy takes into consideration both the history of exposure and the testing. The food challenge is considered the diagnostic gold standard for food allergy. However, recent evidence suggests that not enough challenges are being performed. Several techniques exist with which clinicians can challenge patients. Providers who perform challenges should be familiar with assessing signs and symptoms of a potential reaction and must be prepared to treat anaphylaxis. The magnitude of the serum and skin tests may be of assistance in stratifying a patient’s risk of passing a challenge, and newer diagnostic tests may help better stratify such risk of based on particular epitope recognition.     

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.     

Food allergy and food intolerance: diagnosis and treatment

Food allergy is a matter of concern because it affects about 0.5-3.8% of the paediatric population and 0.1-1% of adults, and as well may cause life-threatening reactions. Skin prick testing with food extracts and with fresh foods, the measurement of food-specific IgE, elimination diets and a double-blind, placebo-controlled food challenge are the main diagnostic procedures; many non-validated procedures are available, creating confusion among patients and physicians. The treatment of food allergy is still a matter of debate. Antihistamines, corticosteroids and, if necessary (in case of anaphylaxis), epinephrine, are the drugs of choice for the treatment of symptoms of food allergy. Sodium cromolyn may be used prophylactically even though there are no controlled studies certifying its efficacy. The only etiologic treatment of food allergy is specific desensitization. Sublingual-oral-specific desensitization has been used by our group for the treatment of food-allergic patients with a high percentage of success.     

The diagnosis and management of egg allergy

Egg allergy is a common food hypersensitivity in children. Atopic dermatitis represents the main clinical manifestation in infancy. On first exposure, many of these infants present with urticaria, angioedema, or anaphylaxis. The role of egg allergy in gastrointestinal conditions is less well understood. The “gold standard” for the diagnosis of egg allergy is the double-blind, placebo-controlled food challenge. Diagnostic cut-off levels have been defined for food-specific serum immunoglobulin E antibody level and skin prick test wheal diameter that predict an adverse challenge outcome. This has significantly reduced the need for formal food challenges. Atopy patch testing, in conjunction with immunoglobulin E-based tests, may further improve the accuracy of predicting a positive challenge. The treatment of egg allergy consists of dietary elimination, or a maternal elimination diet in breast-fed infants. Approximately two thirds of infants with egg allergy will become tolerant by 7 years of age.     

Symptoms of food allergy

Adverse reactions to foods can be due to many causes, but only those involving an immunological mechanism can be defined as food allergic disease. An increasing number of gastrointestinal and other diseases are being shown to involve food intolerances. Immediate reactions with symptoms within hours of eating a particular food are most readily shown to be due to food allergy and are often associated with the presence of food-specific IgE as shown by skin prick tests and RASTs. When reactions are delayed for 24 to 48 hours or more, underlying food intolerance is harder to recognize and much less often shown to be due to allergy. At present, diagnosis and management depends on dietary manipulation, showing that symptoms improve on food avoidance and are reproduced by food challenge (preferably double-blind). Further understanding of the mechanisms involved in food allergy, in Crohn's disease and irritable bowel syndrome may allow the development of simple tests to identify the foods concerned and perhaps, in the case of allergic disease, cure by the induction of tolerance.     

Meeting the nutritional needs of the low-birth-weight infant

Approximately 5% of young children and 3-4% of adults exhibit adverse immune responses to foods in westernized countries, with a tendency to increase. The pathophysiology of food allergy (FA) relies on immune reactions triggered by epitopes, i.e. small amino-acid sequences able to bind to antibodies or cells. Some food allergens share specific physicochemical characteristics that allow them to resist digestion, thus enhancing allergenicity. These allergens encounter specialized dendritic cell populations in the gut, which leads to T-cell priming. In case of IgE-mediated allergy, this process triggers the production of allergen-specific IgE by B cells. Tissue-resident reactive cells, including mast cells, then bind IgE, and allergic reactions are elicited when these cells, with adjacent IgE molecules bound to their surface, are re-exposed to allergen. Allergic reactions occurring in the absence of detectable IgE are labeled non-IgE mediated. The abrogation of oral tolerance which leads to FA is likely favored by genetic disposition and environmental factors (e.g. increased hygiene or enhanced allergenicity of some foods). For an accurate diagnosis, complete medical history, laboratory tests and, in most cases, an oral food challenge are needed. Noticeably, the detection of food-specific IgE (sensitization) does not necessarily indicate clinical allergy. Novel diagnostic methods currently under study focus on the immune responses to specific food proteins or epitopes of specific proteins. Food-induced allergic reactions represent a large array of symptoms involving the skin and gastrointestinal and respiratory systems. They can be attributed to IgE-mediated and non-IgE-mediated (cellular) mechanisms and thus differ in their nature, severity and outcome. Outcome also differs according to allergens.     

Sensitization to Common Food Allergens Is a Risk Factor for Asthma in Young Chinese Children in Hong Kong

Sensitization to aeroallergens is a major risk factor for asthma. Although patients frequently consider food ingestion as an asthma trigger, the relationship between serum food-specific IgE antibodies and childhood asthma in China remains unclear. We therefore conducted a case–control study on asthmatic children attending a university hospital-based outpatient clinic to investigate their pattern of food sensitization. Asthmatic patients underwent spirometric assessment, and peripheral blood was collected for serum-specific IgE antibodies to common food and inhalant allergens. Two hundred and thirty-one asthmatics (aged 9.3±4.3 years) and 79 age- and sex-matched controls were enrolled. The serum logarithmic total IgE concentrations in patients and controls were 2.49 and 1.92, respectively (p<0.0001). Subjects with increased serum total IgE level were significantly more likely to have food sensitization than those with normal values (33% vs. 16%; p = 0.001). Twenty-nine (52%) of 56 asthmatics younger than 6 years old and seven (27%) of 26 age-matched controls had food-specific IgE in their sera (p = 0.035). Asthmatics with food-specific IgE also used more doses of as-needed bronchodilator weekly (p = 0.005). Nonetheless, no association was found between asthma diagnosis and sensitization to individual food allergens. Significant food sensitization, with food-specific IgE level above 95% predictive values for clinical food allergy as proposed by Sampson, was only found in two patients for peanut and three subjects for egg white. In conclusion, a significant association was found between asthma and the presence of food-specific IgE antibodies in young Chinese children. Significant sensitization to common foods is rare in this cohort.     

Food challenge procedure: optimal choices for clinical practice.

The diagnosis of food allergy depends on thorough medical history-taking that may be supplemented with trials of dietary eliminations, skin testing, and specific IgE antibody measurement. However, the reliability of such procedures is often suboptimal. For most cases, oral challenge testing is needed to confirm the diagnosis of food allergy and to identify the causative food(s). Though blinded challenges are ideal, open challenges can be appropriate in some cases, particularly in young children. An optimal design of the procedure would depend on the age of the patient, the anticipated symptoms, and the provoking food quantity. The test is much safer than many surgical and medical procedures being routinely performed. This article presents a practical guideline that can reliably and safely encourage an increased use of this important test in the diagnosis of food allergy.     

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-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.     

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.     

Predictive value of the sulfidoleukotriene release assay in oral allergy syndrome to celery, hazelnut, and carrot.

BACKGROUND: Patients sensitized to birch pollen frequently suffer from a food allergy to plant foods such as celery, carrots, or hazelnut. One of the main manifestations of birch pollen-related food allergy is the oral allergy syndrome. Skin tests and allergen-specific immunoglobulin (Ig) E determinations are poor predictors of such reactions when assessed by double-blind placebo-controlled food challenge (DBPCFC). OBJECTIVE: To investigate whether a cellular test based on leukotriene release from basophils, the cellular antigen stimulation test in combination with enzyme-linked immunosorbent assay (CAST-ELISA), is predictive of pollen-related food allergy. METHODS: Birch pollen-sensitized patients with positive DBPCFC to celery (n=21), hazelnut (n=15), and carrot (n=7) underwent skin tests along with determination of specific IgE and CAST-ELISA for the respective allergens. The results were compared with those of 24 birch pollen-sensitized patients with negative open food challenge to celery, hazelnut, and carrot. RESULTS: While skin prick tests had a sensitivity of 85%, 80%, and 29% for commercial extracts of celery, hazelnut, and carrot, respectively, prick testing with self-prepared extracts yielded sensitivities of 100%, 80%, and 100%, respectively. For specific IgE determinations, sensitivities were 71%, 73%, and 57%, respectively, and the respective specificities were 67%, 73%, and 60%. For CAST-ELISA with various sources and doses of allergens, the sensitivity varied from 71% to 95% for celery, 73% to 80% for hazelnut, and 43% to 86% for carrot. The respective specificities were 67% to 92%, 75% to 88%, and 77% to 91%. Analysis of the predictive value of CAST-ELISA with receiver operating characteristic curves showed that the results of the tests were more predictive of pollen-related food allergy than quantitative allergen-specific IgE determinations. CONCLUSIONS: CAST-ELISA is more specific than routine diagnostic tests for the diagnosis of pollen-related food allergy to celery, hazelnut, and carrot.     

Unproven techniques in allergy diagnosis.

Mainstream allergy diagnosis and treatment is based on classical allergy testing which involves well-validated diagnostic methods and proven methods of treatment. By contrast, a number of unproven tests have been proposed for evaluating allergic patients including cytotoxic food testing, ALCAT test, bioresonance, electrodermal testing (electroacupuncture), reflexology, applied kinesiology a.o. There is little or no scientific rationale for these methods. Results are not reproducible when subject to rigorous testing and do not correlate with clinical evidence of allergy. Although some papers suggest a possible pathogenetic role of IgG, IgG4 antibody, no correlation was found between the outcome of DBPCFC and the levels of either food-specific IgG or IgG4, nor was any difference seen between patients and controls. The levels of these and other food-specific immunoglobulins of non-IgE isotype reflect the intake of food in the individual and may thus be a normal and harmless finding. The so-called "Food Allergy Profile" with simultaneous IgE and IgG determination against more than 100 foodstuffs is neither economical nor useful for diagnosis. DBPCFC must be the reference standard for food hypersensitivity and any new test must be validated by it. As a result, all these unproven techniques may lead to misleading advice or treatments, and their use is not advised.     

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.     

Serum Gliadin Monitoring Extracts Patients with False Negative Results in Challenge Tests for the Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis

BackgroundChallenge testing with wheat plus exercise and/or aspirin is a gold standard for the diagnosis of wheat-dependent exercise-induced anaphylaxis (WDEIA); however, the test may often yield false-negative results. Our previous study suggested that an increase in serum wheat gliadin levels is required to induce allergic symptoms in patients with WDEIA. Based on this knowledge, we sought to extract the patients with false negative results in the challenge tests of WDEIA.MethodsThirty-six patients with suspected WDEIA were enrolled. First, group categorizations—Group I, challenge tests were positive; Group II, challenge tests were negative and serum gliadin were undetectable; Group III, challenge tests were negative and serum gliadin were detectable—were given according to the results of wheat plus exercise and/or aspirin challenge testing and serum gliadin levels. Second, diagnoses were made using retests and/or dietary management in Group II and III.ResultsPositive results for wheat plus exercise and/or aspirin challenge tests gave a diagnosis of definite WDEIA in 17 of 36 patients (Group I). Of the remaining 19 challenge negative patients, serum gliadin was undetectable in ten patients (Group II). Of the ten patients (Group II), three of them were diagnosed as definite WDEIA by retesting and six of them were diagnosed as probable WDEIA using a wheat elimination diet, whereas one patient was non-WDEIA. In the rest of the nine challenge negative patients, serum gliadin was detectable (Group III). No allergic episodes with a normal diet provided a diagnosis of non-WDEIA in seven of the nine patients, whereas the remaining two patients were probable WDEIA or had another food allergy because of repeated episodes.ConclusionsOur study revealed that serum gliadin monitoring during challenge testing is useful.     

Milk-induced wheezing in children with asthma

BackgroundFood allergy has been gaining increasing attention, mostly as causing gastrointestinal and cutaneous reactions. Its role in asthma seems to be under-recognised.ObjectivesThis study's aim is to explore the frequency of involvement of a common food, namely cow's milk, in childhood asthma.Methods32 children (5 months to 11 years; median 24 months; mean 34 months) with asthma and a suspected history of cow's milk allergy were studied. They underwent skin prick testing (SPT) and specific IgE (sIgE) testing to whole cow's milk (WCM), casein, α-lactalbumin, and β-lactoglobulin, followed by single-blind oral milk challenge.ResultsReactions to milk challenge occurred in 12 (37.5%) including wheezing in 5 (41.7%, or 15.6% of the whole group). Children who developed wheezing at the time of challenge were younger than those who had negative challenge (23.0 months vs. 34.8 months). Challenge was positive in 33.3% of subjects who had a positive SPT, and SPT was positive in 50% of challenge-positive subjects. Regarding sIgE, challenge was positive in 26.7% of sIgE-positive subjects, and sIgE was positive in 33.3% of challenge positive subjects. Skin or serum testing with individual protein fractions did not seem to add significant advantage over testing with WCM alone.ConclusionThis study shows that cow's milk can cause wheezing in children with asthma. Although SPT seemed to be more reliable than sIgE testing, both had suboptimal reliability. It is worth considering possible milk allergy in children with asthma, particularly when poorly controlled in spite of proper routine management.