"Atopy patch tests" in the diagnosis of delayed food hypersensitivity

The prevalence of atopic diseases is increasing worldwide. Food allergies are the earliest manifestation of atopy. Atopic eczema affects about 18% of infants in the first 2 years of life and the main cause is allergy to multiple foods. A strong association has been shown between atopic eczema and IgE mediated allergy to milk, egg or peanut, but more than two-thirds of patients intolerant to food proteins have no evidence of IgE sensitization to the relevant food protein. Recently, patch testing with proteins has been found to be helpful in diagnosing food allergy in cases where skin prick tests and estimation of specific antibodies have failed. The methodology of atopy patch test (APT) is unstandardized, and contradictory results have been reported. In contrast to the more standardized APT methodology with aeroallergens, the sensitivities and specificities of food allergens can easily be estimated with food challenge tests. With multiallergic children adding of APTs to the skin prick tests and specific antibody estimation tests give more information for planning a wide enough elimination diet to get the skin and gastrointestinal tract symptomless in order to perform the challenge test which remains the only reliable test for food allergy. Standardization of the APT materials and reading procedure will add to the reliability of this new test method.     

Diagnostic accuracy of atopy patch tests for food allergy in children with atopic dermatitis aged less than two years

BackgroundAtopy patch tests (APT) have been introduced as a valuable tool for the diagnosis of food allergy. However, interpretation of the readout of APT requires further clarification.ObjectiveTo investigate the accuracy of APT in identifying atopic sensitisation to hen's eggs (HE), cow's milk (CM), soybean and wheat in Chinese children with atopic dermatitis (AD) aged less than two years and to evaluate skin signs of APT for accurate diagnosis of food allergy.MethodsAPT was performed and food allergy confirmed by open oral food challenges with HE, CM, soybean and wheat in 150 Chinese AD children aged less than two years. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, positive (LR+) and negative likelihood ratio (LR−) of APT were calculated.ResultsErythema and infiltration were not sufficiently indicative of a positive APT. The PPV increased with the appearance of indurations and the number of papules. The true positive APT rate increased from scores of + to +++. The PPV and specificity were 100% while APT scores of +++ were obtained with HE, CM and wheat. The sensitivity of APT with HE, CM, soybean and wheat allergy ranged from 59.6% to 90.5%, while the specificity ranged from 82.1% to 92.4%.ConclusionThe APT is a suitable method for the diagnosis of AD in Chinese children aged less than two years with food allergies. Erythema and infiltration are not sufficient indicators of APT positivity. The PPV increases with indurations and the number of papules.     

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.     

Double-blind,placebo-controlled food challenges in Brazilian children: Adaptation to clinical practice

BackgroundA double-blind, placebo-controlled food challenge (DBPCFC) is considered the gold standard for diagnosing food allergy, but because of methodological difficulties it is rarely conducted in clinical practice, especially in paediatric patients. The purpose of the study was to propose a DBPCFC protocol that is adapted to our conditions for the diagnosis of an IgE-mediated cow's milk allergy (CMA) in a Brazilian reference centre for paediatric allergies.MethodsThis study includes the experimental phase (choice of materials, adjustments made to protocols described in the literature) and the test execution phase. DBPCFCs were performed in 58 patients aged 1–15 years who were separated into two groups: Group 1 (n = 39), sex 1.6 M:F, 5.3 years median age, suggestive history of IgE-mediated CMA; and Group 2 (n = 19), sex 1.4 M:F, 8.3 years median age with symptoms not associated with milk ingestion and laboratory data not compatible with IgE-mediated CMA.ResultsThe materials were standardised for testing: containers and disposable products, low-lactose cow's milk (CM) and vehicles, such as natural fruit juice, vegetable soup and soybean-based beverages. Each DBPCFC was performed in a single day with two blind, randomised phases with a 2-h interval between them. The milk doses were gradually increased and offered in regular intervals of 15–30 min. Following negative or inconclusive results, patients underwent an open oral challenge test with 200 mL of low-lactose CM.ConclusionsThe proposed adaptation for the DBPCFC allowed to implement this important test for the diagnosis of IgE-mediated CMA in a reference centre for paediatric allergies. It was considered feasible and safe if performed in an appropriate setting with physician supervision.     

Atopy patch test in children with cow's milk and hen's egg allergy: Do clinical symptoms matter?

Introduction and objectivesSince early 2000s, atopy patch test (APT) has been used to determine non-IgE and mixed-type food allergies. Previous studies have reported conflicting results about the diagnostic value of APT in food allergies, due to non-standardized methods.We aimed to determine the diagnostic efficacy of APT compared to open oral food challenge (OFC) in patients diagnosed with cow's milk allergy (CMA) and hen's egg allergy (HEA) manifesting as atopic dermatitis (AD) and gastrointestinal system symptoms.Materials and methodsIn patients with suspected AD and/or gastrointestinal manifestations due to CMA and HEA, the results of OFC, APT, skin prick test (SPT) and specific IgE (sIgE) were reviewed. Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of sIgE, SPT, APT and SPT + APT were calculated.ResultsIn total 133 patients with suspected CMA (80) and HEA (53) were included in the study.In patients with CMA presenting with gastrointestinal symptoms, APT had sensitivity of 9.1%, specificity of 100%, PPV of 100% and NPV of 48.7%. In atopic dermatitis patients, sensitivity of APT was 71.4%, specificity 90.6%, PPV 62.5% and NPV 93.6%.In patients diagnosed with HEA, the sensitivity, specificity, PPV and NPV values of APT were 72.0%, 78.6%, 47.2% and 75.0%, respectively. In patients diagnosed with HEA presenting with AD, sensitivity of APT was 87.5%, specificity 70.6%, PPV 73.7% and NPV 85.7%. Atopy patch test had lower sensitivity (44.4%) and higher specificity (90.9%) in patients diagnosed with HEA presenting with gastrointestinal symptoms than those presenting with AD.ConclusionOur study showed that APT provided reliable diagnostic accuracy in atopic dermatitis patients. However, APT had low sensitivity in patients with gastrointestinal symptoms.     

Allergy to hazelnut in adults: A two-step study

BackgroundAlthough hazelnut consumption is very high in Turkey, the prevalence of hazelnut allergy is still unknown. This study's objective was to investigate the prevalence of hazelnut sensitisation and to verify its clinical importance using double-blind, placebo-controlled challenge (DBPCFC) in an adult population.MethodsPrick-to-prick skin tests were performed with fresh hazelnut in 904 patients admitted to the allergy department. Among the 904 subjects, 20 patients with a history of allergic reactions to hazelnut and/or positive skin tests were recalled for further evaluation. Specific IgE was measured in these subjects. Eleven (11/20) patients accepted to undergo DBPCFC with hazelnut.ResultsAmong the 904 individuals, the history of reactions to hazelnut was positive in 16 subjects (1.8%); prick-to-prick skin tests were positive in 13 (1.4%); prick tests with the commercial product were positive in nine (0.9%); and history plus skin tests were positive in 16 (1.8%). Specific IgE to hazelnut was positive in only three patients. DBPCFC was conducted in 11 subjects with a positivity rate of 63.6% (7/11). We observed six mild and one moderate systemic reactions during the DBPCFC. Among seven subjects with a positive DBPCFC, six (85.7%) had a history of hazelnut allergy, and five (71.4%) had both history and skin test positivity.ConclusionSkin test sensitisation to hazelnut was found to be 1.76% (16/904) which is similar to the sensitisation rate in previous reports. However, DBPCFC was positive in 63% of cases with a history of hazelnut allergy and/or positive skin tests in this study. These results indicate that the presence of history with a positive skin test can be suggestive of hazelnut allergy; however an oral food challenge is needed to confirm the diagnosis.     

Double blind, placebo controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms.

BACKGROUND: The mechanisms for adverse reactions to foods in the gastrointestinal tract are poorly understood. There is conflicting evidence in the literature on the role for IgE mediated allergy in gastrointestinal reactions to staple foods. AIM: The aim was therefore to study the role of IgE mediated allergy in a group of patients with a history of gastrointestinal symptoms related to staple foods (cows' milk, hens' egg, wheat and rye flour) verified in double blind placebo controlled challenges (DBPCFC). PATIENTS: Fifteen patients with DBPCFC, identified by screening of 96 consecutive patients referred to our allergy clinic for investigation of suspected gastrointestinal symptoms due to staple foods. METHODS: The screening included diaries as well as elimination diets and open and blinded food challenges. The frequency of atopy were compared between the double blind positive and double blind negative patients. RESULTS: The positive DBPCFC in the 15 patients included eight patients with milk intolerance, four with wheat flour, two with egg, and one with rye flour. There was no indications of an allergic pathogenesis in all 15 patients with positive DBPCFC, as the skin prick test and radioallergosorbent test were negative for the relevant allergens. The frequency of atopy was four of 21 (19%) in the double blind negative group and three of 15 (20%) in the double blind positive group. CONCLUSION: In adult patients with staple food induced gastrointestinal symptoms, objectively verified by DBPCFC, there were no indications of IgE mediated allergy to the relevant foods suggesting other mechanisms in adults than in children. Future studies may include measures of local events in the shock organs in relation to food intake, for instance utilising inflammatory markers in jejunal fluids.     

特异性口服免疫耐受治疗食物过敏的研究进展

儿童食物过敏(food allergy,FA)发病率有逐年增高趋势,双盲安慰剂激发试验是诊断食物过敏的金标准,回避不适宜食物是目前治疗食物过敏的标准方法.但严格的食物回避依从性较差,可能导致营养不良,长期饮食回避可增加意外摄入时产生严重过敏反应的风险.特异性口服免疫耐受(specific oral tolerance induction,SOTI)通过口服使患者过敏的蛋白抗原,刺激机体形成对该抗原无应答状态,是治疗食物过敏的新方向.由于缺乏双盲安慰剂激发试验,其有效性、安全性以及经济效益仍受到置疑.本文通过对特异性口服免疫耐受的方法、机制以及与传统治疗方法相比较,探讨其临床应用可能性.     

Methodological issues in the diagnostic work-up of food allergy: a real challenge.

The standard of reporting in diagnostic studies has generally been low. Fortunately, this issue has begun to be addressed in recent years through the discussion of important methodological issues in educational series, textbooks, and checklists. Double-blind, placebo-controlled, oral food challenges (DBPCFC) are considered to be the gold standard for diagnosis of food allergy. However, there is no consensus regarding how to interpret the outcome and how to define positive and negative provocations in DBPCFC. Furthermore, since most theories on the diagnosis of food allergy rely on the assumption that the DBPCFC has a high accuracy, this accuracy must be formally statistically evaluated. In this review, we discuss essential methodological issues for diagnostic accuracy studies in general and for oral food challenges in particular and discuss the importance of methodological issues as a guide for forthcoming studies of diagnostic procedures.     

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.     

Low efficacy of atopy patch test in predicting tolerance development in non-IgE-mediated cow's milk allergy

Background

The food atopy patch (APT) test has been used in previous studies to help the diagnosis of non-IgE mediated food allergies (FA). The aim of this study was to evaluate the efficacy of different cow's milk APT preparations to predict oral tolerance in children with previous non-IgE-mediated cow's milk allergy (CMA) diagnosis.

Éducation de l’allergie alimentaire sévère

Families consisting of children with food allergies have significant deficiencies in their knowledge of how to avoid allergen exposure and how to manage allergic reactions. Although an educational program can considerably improve a family's ability to manage allergic reactions to food and reduce the number of reactions, this approach is used too infrequently, even for children who have severe food allergies. A precise diagnosis is essential before undertaking such a program. It can result in reduction of the number of foods to be avoided and improvement in the child's quality of life. We will propose educational objectives for patients with severe food allergies and means to attain these objectives.     

Seafood allergy

Products of the sea are important source of food. Increase in consumption, due to their nutritive value has also led to a great frequency of reactions, including those that are immunologically mediated. Although hypersensitivity reactions to sea products are often easy to identify and can be confirmed by specific in vitro and in vivo tests, some patients can only be diagnosed by double-blind provocation test against placebo (DBPCFC). An atypical or incomplete clinical history suggests, always, contamination with toxins and/or parasites such as Anisakis. Crossed reactivity between different sea products is frequent. However, there are clinical differences between allergy to molluscs, crustaceans and fishes. From precise evaluation of the reactions to sea produce, will result a reduced and reasoned suppression from this type of allergens at food levels.     

Double-blind food challenges in children in general paediatric practice: Useful and safe,but not without pitfalls

ObjectiveTo describe results of double-blind placebo-controlled food challenges (DBPCFC) with cow's milk, hen's egg, soy, peanut and hazelnut in general paediatric practice.MethodsFood challenges were performed between January 2006 and June 2011, in children 0–18 years of age, on two half-day hospital admissions with a one-week interval. Tests were performed in a double-blind fashion following a standardised protocol with validated recipes.ResultsOverall, 234 food challenges were performed in 209 children: 160 with cow's milk, 35 with peanut, 21 with hen's egg, 11 with hazelnuts, and 7 with soy. In two thirds of the cases, the DBPCFC was negative (cow's milk: 57.5%; peanut: 40.0%; hen's egg: 66.7%, hazelnut: 90.9%, soy: 100%). The only patient characteristic significantly associated with a positive DBPCFC was the presence of symptoms from three different organ systems (p = 0.007). Serious systemic allergic reactions with wheeze or anaphylaxis occurred in only two children (0.9%). Symptoms were recorded on 29.3% of placebo days. In 30/137 children with a negative test (22%), symptoms returned when reintroducing the allergen into the diet, mostly (66.7%) transient. Of the 85 tests regarded as positive by the attending physician, 19 (22.4%) did not meet predefined criteria for a positive test. This was particularly common with non-specific symptoms.ConclusionA DBPCFC can be safely performed in a general hospital for a range of food allergens. The test result is negative in most cases except for peanut. Non-specific symptoms may hamper the interpretation of the DBPCFC, increasing the risk of a false-positive result.     

Non–IgE-Mediated Gastrointestinal Food Allergies: Distinct Differences in Clinical Phenotype Between Western Countries and Japan

Non-IgE-mediated gastrointestinal food allergies, including food-protein-induced enterocolitis, enteropathy, proctocolitis and allergic eosinophilic gastroenteritis, seem to be increasing in several regions in the world. However, unlike the case of IgE-mediated food allergy, development of diagnostic laboratory tests and our understanding of the immunological mechanisms involved in non-IgE-mediated gastrointestinal food allergies lag. Although the clinical entities in Western countries have been well established, the clinical phenotypes might differ somewhat among the human races and geographical regions. In Japan, non-IgE-mediated gastrointestinal food allergies have increased sharply since the late 1990s, and clinicians have sometimes experienced confusion because of differences in the clinical phenotypes from those seen in Western countries. Aiming to solve this problem, we performed clinical research and determined a useful method for dividing patients into four clusters with distinctive clinical symptoms. We are confident this method will help in diagnosing and treating these patients. We also tried to clarify the differences between these patients in Japan and Western countries.     

The use of patch testing in the diagnosis of food allergy

Diagnosing food allergies can be challenging to the practitioner. Our armamentarium includes standardized skin prick testing, radioallergoimmunosorbent (RAST) testing, and food challenges. These methods have certainly been helpful in the IgE-mediated disorders, including urticaria and anaphylaxis. However, diagnosing patients who have the non-IgE (cellmediated) or mixed (IgE and cell-mediated) disorders remains challenging with our current diagnostic methods. Recent studies have examined the use of patch testing for these foodallergic patients, specifically those with atopic dermatitis and eosinophilic esophagitis. In this article, we review literature regarding patch testing: its methods, its statistical usefulness, and its potential future role.     

Mastocytosis and adverse reactions to biogenic amines and histamine-releasing foods: what is the evidence?

BACKGROUND: It has been suggested that normal concentrations of biogenic amines and 'histamine-releasing foods' may exacerbate symptoms in mastocytosis. The purpose of this study was to look for scientific evidence in the literature on diets restricted in biogenic amines and histamine-releasing foods in the treatment of mastocytosis. METHODS: Medline (1966 to 2004), Cinahl (1982 to 2004) and the Cochraine Library were searched for double-blind placebo-controlled food challenge (DBPCFC) studies with biogenic amines and/or histamine-releasing foods in mastocytosis. RESULTS: No studies employing DBPCFC with dietary biogenic amines or histamine-releasing foods in mastocytosis were found. Only a few in vitro studies in other diseases, animal studies and studies in humans in which histamine-releasing agents were incubated directly with duodenal tissues were found. One case was reported of severe adverse reactions to alcohol in mastocytosis, objectified by an open challenge. CONCLUSION: Despite the widespread belief that biogenic amines and histamine-releasing foods may cause allergy-like, non-IgE-mediated symptoms in certain patients, the role of diets restricted in biogenic amines and histamine-releasing foods in the treatment of mastosytosis remains hypothetical but worthy of further investigation. There is some evidence for adverse reactions to alcohol in mastocytosis.     

Lethal or life-threatening allergic reactions to food.

Fatal or life-threatening anaphylactic reactions to food occur in infants, children and adults. Atopic individuals with bronchial asthma and prior allergic reactions to the same food are at a particularly high risk, whereby even the mere inhalation of the allergenic food can be fatal. Not only peanuts, seafood and milk can induce severe, potentially lethal anaphylaxis, but indeed a wide spectrum of foods, according to the different patterns of food sensitivity in different countries. Foods with "hidden" allergens and meals at restaurants are particularly dangerous for patients with food allergies. Similarly, schools, public places and restaurants are the major places of risk. However, the main factor contributing to a fatal outcome is the fact that the victims did not carry their emergency kit with adrenaline (epinephrine) with them. In cases of death where food anaphylaxis is suspected, it is important for forensic reasons to preserve uneaten portions of the food in order to identify (hidden) allergens. It is also important to determine postmortem specific serum IgE, tryptase and histamine levels to document the anaphylaxis. There is a need to raise awareness of the diagnosis and treatment of anaphylaxis among doctors, those called upon to administer emergency medical care, and the public, and also to provide increased support for those with potentially fatal food allergies through the help of patients' organizations, and national and international medical societies. The food industry should ensure a policy of comprehensive labelling of ingredients so that even the smallest amount of potentially lethal foodstuffs can be clearly identified. Finally, the pharmaceutical industry should be persuaded to reintroduce an adrenaline inhaler onto the market.     

Discrepancies between reported food intolerance and sensitization test findings in irritable bowel syndrome patients

OBJECTIVE: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with clinical signs typical of "intestinal" food allergies or intolerance. The aim of this study was to characterize the clinical features of IBS patients suspected of suffering from adverse reactions to food. METHODS: The study involved 128 consecutive IBS patients divided into four groups according to their main symptom on presentation at our outpatient clinic. A detailed medical history was recorded, paying particular attention to any allergies and reported intolerance to food. Each patient was screened for allergies; intestinal permeability tests was performed in randomly selected patients from different groups. Findings were analyzed using the chi2 test. RESULTS: Adverse reactions to one or more foods were reported by 80 patients (62.5%); skin prick tests (SPT) were positive in 67 patients (52.3%) with no significant differences between patients complaining of different symptoms. Patients who reported a food intolerance had more positive SPTs than those who did not (47 of 80 [58.7%] vs 20 of 48 [41.7%]); this difference was not statistically significant, although it suggests a trend (p < 0.0610). There was little consistency between the specific foods reported to cause intolerance and those resulting from the tests (11 of 80 patients, 13.7%). The intestinal permeability test was normal in 29 of 33 patients (87.9%). CONCLUSIONS: More than 50% of IBS patients were found sensitized to some food or inhalant without any typical clinical signs. Patients were unable to identify potentially offending foods. The lack of a correlation between SPT results and reported food allergies needs further investigation to clarify the pathophysiology and improve the diagnosis of intestinal food allergies.     

Genetics of food allergy

Allergic reactions to foods are an important medical problem throughout the industrialized world. The occurrence of food allergy appears to be strongly in.uenced by genetics, but the basis of the genetic predisposition to food allergy has not been differentiated from that for atopy in general. In addition, genetic susceptibility alone does not explain the prevalence of food allergy satisfactorily, leaving ample room to consider the importance of environmental in.uences (external, maternal, and gastrointestinal environment) and interactions between the host and the environment. Several features of food allergy are highlighted in this review: 1) patients with severe food allergies are overwhelmingly atopic, but food allergy occurs only in approximately 10% of patients with other atopic diseases; 2) most patients are clinically reactive to a single food, and although a substantial minority have multiple food allergies, the variety of bonefide food allergies in a given individual is limited; 3) foods contain multiple proteins whereas only a small subset are allergenic; 4) there is likely an important contribution of the environment, becoming manifest in genetically susceptible individuals.