"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.     

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.     

食物抗原特异性IgG和IgE在功能性胃肠病发病中的作用

背景：许多功能性胃肠病患者于进食某些食物后出现症状加重。目的：测定肠易激综合征（IBS）和功能性消化不良（FD）患者的血清食物抗原特异性IgG和IgE，探讨食物过敏在功能性胃肠病发病中的作用。方法：符合罗马Ⅱ标准的37例IBS患者、28例FD患者以及20例健康志愿者纳入本研究。以酶联免疫吸附测定（ELISA）检测受试者血清中14种食物抗原特异性IgG和IgE，同时测定血清总IgE水平。通过问卷调查行症状评分，分析血清食物抗原特异性IgG水平与症状总评分的相关性。结果：与健康对照组相比，IBS组血清中螃蟹、鸡蛋、河虾、大豆和小麦抗原特异性IgG水平显著升高（P〈0．05），FD组血清中鸡蛋和大豆抗原特异性IgG水平显著升高（P〈0．05）。三组间血清总IgE水平和食物抗原特异性IgE阳性率差异无统计学意义。IBS组和FD组血清食物抗原特异性IgG水平与症状总评分之间无明显相关性。结论：IBS和FD患者血清中部分食物抗原特异性IgG水平显著升高．提示IgG介导的食物过敏可能是功能性胃肠病潜在的发病机制之一。     

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 allergy: new insights into pathophysiology and clinical perspectives

Adverse reactions to food that result in gastrointestinal symptoms are common in the general population; while only a minority of such individuals will have symptoms due to immunologic reactions to foods, gastrointestinal food allergies do exist in both children and adults. These immune reactions are mediated by immunoglobulin E-dependent and -independent mechanisms involving mast cells, eosinophils, and other immune cells, but the complexity of the underlying mechanisms of pathogenesis have yet to be fully defined. Knowledge of the spectrum of adverse reactions to foods that affect the digestive system, including gastrointestinal food allergy, is essential to correctly diagnose and manage the subset of patients with immunologically mediated adverse reactions to foods. Potentially fatal reactions to food necessitate careful instruction and monitoring on the part of health care workers involved in the care of individuals at risk of anaphylaxis. New methods of diagnosis and novel strategies for treatment, including immunologic modulation and the development of hypoallergenic foods, are exciting developments in the field of food allergy.     

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.     

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.     

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.     

Patch test in the diagnosis of food allergy

Double-blind, placebo-controlled food challenges (DBPCFC) are the gold standard method for diagnosing food allergies. However, due to the difficulty of their performance on routine clinic, there is a need for laboratory tools in order to minimise the frequency of DBPCFC. Atopy patch test (APT) represents a promising manner of diagnosing delayed-type allergic reactions. The APT may identify patients with food allergies with negative specific IgE. However, the clinical relevance of positive APT reactions is still to be proven by standardised outcome definitions.     

HRQoL questionnaire evaluation in lactose intolerant patients with adverse reactions to foods

The occurrence of patients with gastrointestinal symptoms attributed either to food allergy or intolerance has significantly increased. Nevertheless, an accurate and detailed case history, a systematic evaluation and the outcomes of specific allergy tests to identify the offending foods, including “in vivo” and “in vitro” allergy tests, are often negative for food allergy and may indicate a lactose intolerance, which is a recurrent condition affecting about 50% of adults. The aims of our study were the following: (1) What is the real incidence of the food hypersensitivity and the primary lactose intolerance in patients with gastrointestinal symptoms, initially referred to allergy or food intolerance? (2) Does lactose intolerance affect the quality of life and compliance to the therapy program? We investigated 262 consecutive patients, 72 men and 190 women. An accurate and detailed history and clinical examination were completed to investigate the offending foods. The evaluation in each patient included: allergy tests, lactose H₂ breath test (LHBT) and the HRQoL questionnaire. Five years after the diagnosis of lactose intolerance, a questionnaire on the persistence of gastrointestinal symptoms after lactose ingestion and the diet compliance was distributed. Our results demonstrate an high prevalence of lactose intolerance, more frequent in women; in these patients, bloating and diarrhea are the most reported symptoms. We observe only a significant positive correlation between adverse drug reaction (ADR) and LHBT+ patients, but not an augmented prevalence of food allergy and a negative impact on the HRQoL questionnaire of lactose intolerance.     

Specific food intolerance: its place as a cause of gastrointestinal symptoms.

Thirteen out of 49 patients suspected of having specific food intolerance after withdrawal and reintroduction of specific foods, were further subjected to double blind placebo controlled food challenges. Only three of these subjects were thus shown to have proven specific food intolerance. Of the remaining 10, nine were strong 'placebo reactors'. The study suggests that a small number of patients with gastrointestinal symptoms have verifiable specific food intolerance but that a greater number have symptoms attributable to psychogenic causes.     

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.     

Symptoms discriminate irritable bowel syndrome from organic gastrointestinal diseases and food allergy

BACKGROUND: The value of specific gastrointestinal symptoms in discriminating irritable bowel syndrome (IBS) from organic disease has been documented. In contrast, there have been few attempts to identify symptoms that discriminate irritable bowel syndrome from food allergy, despite similarities in their respective symptom complexes. We aimed to investigate the value of symptoms in discriminating irritable bowel syndrome from organic disease and food allergy. METHODS: Subjects (n = 288) were recruited from consecutive patients presenting to the Internal Medicine, Gastroenterology and Allergy Units in Chieti. Patients completed the validated Bowel Disease Questionnaire (BDQ) prior to an independent diagnostic evaluation, which included endoscopy when appropriate. Food allergy was diagnosed using a 2-week elimination diet, followed by a placebo-controlled food challenge test, a skin prick test and serum RAST for specific IgE for suspected foods or additives. The results of the BDQ were not considered in formulating a diagnosis. In total, 99 patients were diagnosed with the IBS, 79 patients were diagnosed with organic disease and 22 patients were diagnosed with food allergy. A further 88 patients with extraintestinal allergies were included as a control group. RESULTS: Based on logistic regression analysis, six symptom items discriminated IBS from organic disease, while five symptoms discriminated patients with IBS from control subjects. A diagnosis of IBS compared to organic disease was positively associated with straining on defaecation (P=0.0001), diarrhoea (P=0.001) and abdominal bloating (P=0.01), but was negatively associated with pain in the upper abdomen (P=0.0004), reflux (P=0.0001) and appetite loss (P=0.004). A diagnosis of IBS compared to extraintestinal allergy was positively associated with pain relieved by bowel movement (P=0.0001), pain in the lower abdomen (P=0.0006), pain in both the upper and lower abdomen (P=0.003), frequent pain (P=0.001) and abdominal bloating (P=0.0009). In comparison between IBS and food allergy patients, a diagnosis of IBS was positively associated with pain in the lower abdomen (P=0.001), pain relieved by bowel movements (P=0.001), frequent pain (P=0.02) and abdominal bloating (P=0.03). CONCLUSION: Symptoms appear to be useful for discriminating IBS from organic gastrointestinal disease and food allergy.     

Food allergy to wheat flour in adults

Wheat flour is a basic foodstuff. Food allergy has been especially described in children, in the form of atopic dermatitis. Food allergy in adults is rare and especially described in the form of anaphylactic shock sometimes induced by effort. Four observations of adult food allergy are presented. The IgE dependent mechanism is documented. The positive oral provocation tests needed doses of 17 to 30 grams. One crossed sensitivity between rye and barley was seen. The major allergen was probably gluten, particularly gliadines. Sensitization was probably due to prolonged inhalation of wheat flour. The authors stress the possibility of food allergy to wheat flour by other mechanisms, the difficulty of diagnosis, needed for a diet without cereal and gluten that is now non reimbursable.     

Gastrointestinal Food Allergy in Infants

Food allergies are classified into three types, “IgE-mediated,” “combined IgE- and cell-mediated” and “cell-mediated/non-IgE-mediated,” depending on the involvement of IgE in their pathogenesis. Patients who develop predominantly cutaneous and/or respiratory symptoms belong to the IgE-mediated food allergy type. On the other hand, patients with gastrointestinal food allergy (GI allergy) usually develop gastrointestinal symptoms several hours after ingestion of offending foods; they belong to the cell-mediated/non-IgE-mediated or combined IgE- and cell-mediated food allergy types. GI allergies are also classified into a number of different clinical entities: food protein-induced enterocolitis syndrome (FPIES), food protein-induced proctocolitis (FPIP), food protein-induced enteropathy (Enteropathy) and eosinophilic gastrointestinal disorders (EGID). In the case of IgE-mediated food allergy, the diagnostic approaches and pathogenic mechanisms are well characterized. In contrast, the diagnostic approaches and pathogenic mechanisms of GI allergy remain mostly unclear.In this review, we summarized each type of GI allergy in regard to its historical background and updated clinical features, offending foods, etiology, diagnosis, examinations, treatment and pathogenesis. There are still many problems, especially in regard to the diagnostic approaches for GI allergy, that are closely associated with the definition of each disease. In addition, there are a number of unresolved issues regarding the pathogenic mechanisms of GI allergy that need further study and elucidation. Therefore, we discussed some of the diagnostic and research issues for GI allergy that need further investigation.     

Prevalence of allergen-specific IgE among patients with chronic fatigue syndrome.

The prevalence of atopy among patients having chronic fatigue syndrome (CFS) has been reported to be as high as 80% in published surveys of patients with this syndrome. However, many of the reports relied on self-assessment by patients for the presence of atopy or solely used total immunoglobulin E (IgE) levels to assess the likelihood of atopy. To more critically assess the presence of atopy among patients with CFS, testing was done for total IgE and allergen-specific IgE using the Pharmacia CAP system including 20 common allergens: trees (birch/oak/ash), grass (rye/blue), weeds (common/giant ragweed), molds (Penicillium/Aspergillus/Alternaria), dust mites (Dermatophagoides pteronyssinus/Dermatophagoides farinae), animal dander (cat/dog), and foods (egg white/milk/wheat/corn/peanut/shrimp). Testing of 50 patients having documented CFS indicated that 78% had total IgE < 100 IU/mL, among whom 26% had a positive test for allergen-specific IgE of class I or greater for one or more allergens. Among the 22% of CFS patients having a total IgE > 100 IU/mL, 73% had a positive test for allergen-specific IgE for one or more allergens. The most commonly positive allergens were dust mites (24-26%), whereas molds (0-6%) and foods (0-4%) were rarely positive. The overall frequency of positive results for the presence of allergen-specific IgE among CFS patients was 36%, not significantly different from the normal prevalence of these antibodies in the general population (20-35%). This assessment of the prevalence of allergen-specific IgE antibodies in patients with CFS fails to support a potential association between CFS and atopy.     

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.     

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 guidelines for food allergy 2020

Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible.