Skin prick test to egg white provides additional diagnostic utility to serum egg white-specific IgE antibody concentration in children

BACKGROUND: Levels of IgE antibody to egg white of greater than 7 kIU/L are highly predictive of clinical reactivity to egg, and lower levels often require evaluation with oral food challenge (OFC) to establish definitive diagnosis. OFCs have inherent risks, and diagnostic criteria indicating high likelihood of passing would be clinically useful. OBJECTIVE: We sought to determine whether the size of the skin prick test (SPT) to egg white adds diagnostic utility for children with low egg white-specific IgE antibody levels. METHODS: A retrospective analysis of clinical history, egg white-specific IgE antibody levels, SPT responses, and egg OFC outcomes was performed. RESULTS: Children who passed (n = 29) egg OFCs and those who failed (n = 45) did not differ significantly in age, clinical characteristics, or egg white-specific IgE levels. There were, however, significant differences between both egg white SPT wheal response size and egg/histamine SPT wheal index. Children who failed egg OFCs had a median wheal of 5.0 mm; those who passed had a median wheal of 3.0 mm (P = .003). Children who failed egg OFCs had a median egg/histamine index of 1.00; those who passed had a median index of 0.71 (P = .001). For egg white-specific IgE levels of less than 2.5 kIU/L, an SPT wheal of 3 mm or an egg/histamine index of 0.65 was associated with a 50% chance of passing. CONCLUSION: In children with low egg white-specific IgE levels, those with smaller SPT wheal responses to egg were more likely to pass an egg OFC than those with larger wheal responses. The size of the egg white SPT response might provide additional information to determine the timing of egg OFC. CLINICAL IMPLICATIONS: The size of the egg white SPT wheal response might provide the clinician with additional information to determine the timing of egg OFC in children with low egg white-specific IgE antibody levels.     

Road map for the clinical application of the basophil activation test in food allergy

The diagnosis of IgE‐mediated food allergy based solely on the clinical history and the documentation of specific IgE to whole allergen extract or single allergens is often ambiguous, requiring oral food challenges (OFCs), with the attendant risk and inconvenience to the patient, to confirm the diagnosis of food allergy. This is a considerable proportion of patients assessed in allergy clinics. The basophil activation test (BAT) has emerged as having superior specificity and comparable sensitivity to diagnose food allergy, when compared with skin prick test and specific IgE. BAT, therefore, may reduce the number of OFC required for accurate diagnosis, particularly positive OFC. BAT can also be used to monitor resolution of food allergy and the clinical response to immunomodulatory treatments. Given the practicalities involved in the performance of BAT, we propose that it can be applied for selected cases where the history, skin prick test and/or specific IgE are not definitive for the diagnosis of food allergy. In the cases that the BAT is positive, food allergy is sufficiently confirmed without OFC; in the cases that BAT is negative or the patient has non‐responder basophils, OFC may still be indicated. However, broad clinical application of BAT demands further standardization of the laboratory procedure and of the flow cytometry data analyses, as well as clinical validation of BAT as a diagnostic test for multiple target allergens and confirmation of its feasibility and cost‐effectiveness in multiple settings.     

Utility of food-specific IgE concentrations in predicting symptomatic food allergy

BACKGROUND: The double-blind, placebo-controlled food challenge is considered the gold standard for diagnosing food allergy. However, in a retrospective analysis of children and adolescents with atopic dermatitis and food allergy, discrete food-specific IgE concentrations were established that could predict clinical reactivity to egg, milk, peanut, and fish with greater than 95% certainty. OBJECTIVE: The purpose of this investigation was to determine the utility of these 95% predictive decision points in a prospective evaluation of food allergy. METHODS: Sera from 100 consecutive children and adolescents referred for evaluation of food allergy were analyzed for specific IgE antibodies to egg, milk, peanut, soy, wheat, and fish by using the Pharmacia CAP System FEIA. Food-specific IgE values were compared with history and the results of skin prick tests and food challenges to determine the efficacy of previously established 95% predictive decision points in identifying patients with increased probability of reacting during a specific food challenge. RESULTS: One hundred children (62% male; median age, 3.8 years; range, 0.4-14.3 years) were evaluated for food allergy. The diagnosis of food allergy was established by means of history or oral food challenge. On the basis of the previously established 95% predictive decision points for egg, milk, peanut, and fish allergy, greater than 95% of food allergies diagnosed in this prospective study were correctly identified by quantifying serum food-specific IgE concentrations. CONCLUSION: In a prospective study of children and adolescents referred for evaluation of food allergy, previously established 95% predictive decision points of food-specific IgE antibody concentrations for 4 major food allergens were effective in predicting clinical reactivity. Quantification of food-specific IgE is a useful test for diagnosing symptomatic allergy to egg, milk, peanut, and fish in the pediatric population and could eliminate the need to perform double-blind, placebo-controlled food challenges in a significant number of children.     

Oral food challenges: Special considerations

ObjectiveTo reinforce special considerations when offering and conducting oral food challenges (OFCs).Data SourcesPublished studies and reviews.Study SelectionsStudies concerning OFCs and their conduct.ResultsMultiple OFC protocols for various clinical situations and foods were reviewed.ConclusionOFCs are used for the definitive diagnosis of food allergy. Risk and benefit assessment guide the OFC procedure. The conduct of OFCs is influenced by multiple factors, including age, food, and goal of the challenge.     

Late eczematous reactions to food in children with atopic dermatitis

BACKGROUND: Food allergy is a common problem in patients with atopic dermatitis (AD), particularly in children. While immediate reactions to food are well characterized, the importance of food as a provocation factor for late eczematous reactions has been a subject of debate for several decades. OBJECTIVE: To investigate the importance of food for the induction of late eczematous reactions in children with AD and to correlate the clinical outcome to the results of specific IgE determinations and atopy patch tests (APTs). METHODS: One hundred and six double-blind placebo-controlled food challenges (DBPCFCs) to cow's milk, hen's egg, wheat and soy in 64 children with AD (median age 2 years) were analysed retrospectively. Total and food-specific IgE were determined by CAP RAST FEIA and APTs with native foodstuff were performed. The diagnostic values of specific IgE and APT results were calculated. RESULTS: Forty-nine (46%) of the challenges were related to a clinical reaction. An exacerbation of AD (late eczematous reaction) commonly occurred 24 h after the ingestion of food. Isolated late eczematous reactions were seen in 12% of all positive challenges. Forty-five percent of the positive challenges were associated with late eczematous responses, which followed immediate-type reactions. The sensitivity of food-specific IgE and the APT was 76% and 70%, respectively. Specific IgE and APT were often false positive, which resulted in low positive predictive values (64% and 45%, respectively). CONCLUSIONS: Late eczematous reactions may often be observed upon food challenge in children with AD. Due to the poor reliability of food-specific IgE and APT results DBPCFCs have still to be regarded as the gold standard for the appropriate diagnosis of food responsive eczema in children with AD.     

Diagnosis of food allergy based on rectal mucosal cytology]

We performed rectal and/or oral challenge tests on 8 patients with suspected but unproven diagnosis of food allergy based on detailed medical history and findings from radioallergosorbent tests (RAST). The cells appearing in the rectal mucosal smear serially for 48 hours after allergen challenge were examined. The following results were obtained: 1) Significant numbers of not only eosinophils but also mast cells appeared in the rectal smears after challenges with suspected-food allergens, but not with unrelated foods. This confirmed the antigen-specificity of the method. 2) In some cases, the appearance of mast cells and eosinophils was bimodal, suggesting the existence of a later allergic response in addition to an immediate-type reaction. 3) The food-specific appearance of mast cells and eosinophils was observed in association with clinical symptoms after challenge, even in patients whose IgE antibodies to the allergen were negative or commercially unavailable. In conclusion, we propose that rectal mucosal cytology in conjunction with rectal and/or oral challenge tests is a reliable and objective method to diagnose unproven or suspected food allergy.     

Interpreting IgE sensitization tests in food allergy

Food allergies are increasing in prevalence, and with it, IgE testing to foods is becoming more commonplace. Food-specific IgE tests, including serum assays and prick skin tests, are sensitive for detecting the presence of food-specific IgE (sensitization), but specificity for predicting clinical allergy is limited. Therefore, positive tests are generally not, in isolation, diagnostic of clinical disease. However, rationale test selection and interpretation, based on clinical history and understanding of food allergy epidemiology and pathophysiology, makes these tests invaluable. Additionally, there exist highly predictive test cutoff values for common allergens in atopic children. Newer testing methodologies, such as component resolved diagnostics, are promising for increasing the utility of testing. This review highlights the use of IgE serum tests in the diagnosis of food allergy.     

Total serum IgE level influences oral food challenge tests for IgE‐mediated food allergies

Probability curves predicting oral food challenge test (OFC) results based on specific IgE levels are widely used to prevent serious allergic reactions. Although several confounding factors are known to affect probability curves, the main factors that affect OFC outcomes are currently unclear. We hypothesized that an increased total IgE level would reduce allergic reactivity. Medical records of 337 and 266 patients who underwent OFCs for 3.5 g boiled hen's egg white and 3.1 ml raw cow's milk, respectively, were examined retrospectively. We subdivided the patients into three groups based on total IgE levels and age by percentile (<25th, 25–75th, and >75th percentiles), and logistic regression analyses were performed on each group. Patients with higher total IgE levels were significantly less responsive. In addition, age did not significantly affect the OFC results. Therefore, total IgE levels should be taken into account when predicting OFC results based on food‐specific IgE levels.     

Predicting the outcome of oral food challenges with hen's egg through skin test end-point titration

Background Oral food challenge (OFC) is the diagnostic 'gold standard' of food allergies but it is laborious and time consuming. Attempts to predict a positive OFC through specific IgE assays or conventional skin tests so far gave suboptimal results.
Objective To test whether skin test with titration curves predict with enough confidence the outcome of an oral food challenge.
Methods Children ( n =47; mean age 6.2 ± 4.2 years) with suspected and diagnosed allergic reactions to hen's egg (HE) were examined through clinical history, physical examination, oral food challenge, conventional and end-point titrated skin tests with HE white extract and determination of serum specific IgE against HE white. Predictive decision points for a positive outcome of food challenges were calculated through receiver operating characteristic (ROC) analysis for HE white using IgE concentration, weal size and end-point titration (EPT).
Results OFC was positive (Sampson's score 3) in 20/47 children (42.5%). The area under the ROC curve obtained with the EPT method was significantly bigger than the one obtained by measuring IgE-specific antibodies (0.99 vs. 0.83, P <0.05) and weal size (0.99 vs. 0.88, P <0.05). The extract's dilution that successfully discriminated a positive from a negative OFC (sensitivity 95%, specificity 100%) was 1 : 256, corresponding to a concentration of 5.9 μg/mL of ovotransferrin, 22.2 μg/mL of ovalbumin, and 1.4 μg/mL of lysozyme.
Conclusion EPT is a promising approach to optimize the use of skin prick tests and to predict the outcome of OFC with HE in children. Further studies are needed to test whether this encouraging finding can be extended to other populations and food allergens.     

Characteristics of tree nut challenges in tree nut allergic and tree nut sensitized individuals

Background

Characteristics and outcomes of tree nut (TN) oral food challenges (OFCs) in patients with TN allergy or sensitization alone are poorly studied.

Do we have suitable in-vitro diagnostic tests for the diagnosis of food allergy?

PURPOSE OF REVIEW: Positive standardized food challenges represent the gold standard of diagnostic procedures in food-related reactions suspected to be of allergic nature. Skin prick testing and in-vitro diagnosis is helpful in most cases and can help to avoid cumbersome food challenges. This review considers recent progress in the use of in-vitro tests in the diagnosis of food allergy. RECENT FINDINGS: Recent studies have addressed the characterization of 'new' food allergens which might now be used more accurately in the in-vitro diagnosis of food allergy. Additionally, while in-vitro tests must always be interpreted in line with the allergen tested and the clinical history, levels of food-specific immunoglobulin E can be correlated with the outcome of challenges to foods such as tree nuts as well as egg, according to two recent studies. Finally, epitope binding patterns of specific food allergens might help to predict which patients will most likely outgrow their food allergy, or which patients are clinically tolerant. This might help to avoid food challenges, which carry a risk for a potentially severe outcome. SUMMARY: Recent studies of in-vitro diagnosis of food allergy have helped to provide safer and more accurate tests in the diagnosis and prognosis of food allergy.     

The relationship of allergen-specific IgE levels and oral food challenge outcome

BACKGROUND: Oral food challenges remain the gold standard for the diagnosis of food allergy. However, clear clinical and laboratory guidelines have not been firmly established to determine when oral challenges should be performed. OBJECTIVE: We sought to determine the value of food-specific IgE levels in predicting challenge outcome. METHODS: A retrospective chart review of 604 food challenges in 391 children was performed. All children had food-specific IgE levels measured by means of CAP-RAST before challenge. Data were analyzed to determine the relationship between food-specific IgE levels and challenge outcome, as well as the relationship between other clinical parameters and challenge outcome. RESULTS: Forty-five percent of milk challenges were passed compared with 57% for egg, 59% for peanut, 67% for wheat, and 72% for soy. Specific IgE levels were higher among patients who failed challenges than among those who passed (P 相似文献   

Food-specific serum immunoglobulin E measurements in children presenting with food allergy

BackgroundIn children with food allergy, multiple food-specific serum IgE levels to common food allergens are frequently measured.ObjectiveTo compare food-specific serum IgE measurements among common food allergens in children with food allergy to determine the characteristics of the measurements, their ability to discriminate between foods associated and not associated with a presenting clinical reaction, and their change over time.MethodsA retrospective analysis was conducted of food-specific serum IgE to cow's milk, egg white and yolk, peanuts, almond, and soy, for up to 3 subsequent measurements, in 291 children with food allergy. A food-specific serum IgE level lower than 0.35 kU/L was considered a negative measurement. The correlation of IgE measurements with presenting symptoms was conducted for each food in 172 children.ResultsOf 1,312 food-specific serum IgE measurements, 69.8% were positive. The median (interquartile range) IgE level for foods associated with the presenting complaint was 7.3 kU/L (2.7–31) and that for foods not associated with a clinical complaint was 2.2 kU/L (0.38–13). The difference was statistically significant (P = .01) only for cow's milk. Specific IgE levels were highest for peanuts, followed by cow's milk, eggs, soy, and almonds, and trended upward over time.ConclusionIn children presenting with clinical symptoms of a reaction to a food allergen, measurements of food-specific serum IgE to other common food allergens are commonly positive. An increase in food-specific serum IgE occurs over time.     

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2007

This review highlights some of the research advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects that were reported primarily in the Journal in 2007. Advances in diagnosis include possible biomarkers for anaphylaxis, improved understanding of the relevance of food-specific serum IgE tests, identification of possibly discriminatory T-cell responses for drug allergy, and an elucidation of irritant responses for vaccine allergy diagnostic skin tests. Mechanistic studies are discerning T-cell and cytokine responses central to eosinophilic gastroenteropathies and food allergy, including the identification of multiple potential therapeutic targets. Regarding treatment, clinical studies of oral immunotherapy and allergen vaccination strategies show promise, whereas several clinical studies raise questions about whether oral allergen avoidance reduces atopic risks and whether probiotics can prevent or treat atopic disease. The importance of skin barrier dysfunction has been highlighted in the pathogenesis of atopic dermatitis (AD), particularly as it relates to allergen sensitization and eczema severity. Research has also continued to identify immunologic defects that contribute to the propensity of patients with AD to have viral and bacterial infections. New therapeutic approaches to AD, urticaria, and angioedema have been reported, including use of sublingual immunotherapy, anti-IgE, and a kallikrein inhibitor.     

Food allergy – accurately identifying clinical reactivity

Up to 25% of adults believe that they or their children are afflicted with a food allergy. However, the actual prevalence of food allergy is much lower: approximately 6–8% of children suffer from food allergy during their first 3 years of life, and many children then develop clinical tolerance. Food allergy encompasses a whole spectrum of disorders, with symptoms that may be cutaneous, gastrointestinal or respiratory in nature. Food disorders also differ according to the extent that they are immunoglobulin E (IgE)-mediated. Skin-prick testing is often used to identify food sensitization, although double-blind, placebo-controlled food challenge (DBPCFC) tests remain the gold standard for diagnosis. Recent evidence suggests that quantitative IgE measurements can predict the outcome of DBPCFC tests and can replace about half of all oral food challenges. When an extensive medical history is obtained in combination with IgE quantification, even fewer patients may require formal food challenges. It has also become possible to map the IgE-binding regions of many major food allergens. This may help to identify children with persistent food allergy, as opposed to those who may develop clinical tolerance. In future, microarray technology may enable physicians to screen patients for a large number of food proteins and epitopes, using just a few drops of blood.     

Review of 400 consecutive oral food challenges to almond

Background

Diagnosis of almond allergy is complicated by a high rate of false-positive test results. Accurate diagnosis of almond allergy is critical because almond is a source of nutrition and milk products for children with other food allergies.

Threshold levels in food challenge and specific IgE in patients with egg allergy: is there a relationship?

BACKGROUND: Previously published articles described a relationship between food-specific IgE and the outcome of food challenge in children with egg allergy. These investigations defined different levels of predictive values in different study populations and thus pointed toward the possibility of a certain level of specific IgE to egg white predicting a positive outcome in food challenge. OBJECTIVE: The purpose of this study was to determine the utility of specific IgE in estimating threshold level to predict a positive outcome in food challenge. METHODS: Fifty-six children were evaluated for egg allergy by titrated oral challenges. Sera were analyzed for specific IgE to egg white in 56 patients by using the Magic Lite test and 32 of 56 patients also by the CAP test. Values of specific IgE to egg white were compared to the outcome of challenges and the threshold level. RESULTS: The diagnostic level of specific IgE predicting clinical reactivity in this population with greater than 95% certainty was identified as 10.8 standardized units/mL (Magic Lite) and 1.5 kilounits of allergen-specific IgE/L (CAP), respectively. We found no significant relationship between the specific IgE concentration (egg white) and the challenge threshold level. CONCLUSION: Although the specific IgE concentration correlated to a positive outcome in food challenge, there was no significant relationship between the quantification of specific IgE and the challenge threshold level. Therefore the standardized food challenge still remains the gold standard in the diagnosis of food allergy.     

Effects of food allergens on asthma exacerbations in schoolchildren with atopic asthma

Although the prevalence with which food causes asthma is not well known, food allergy is implicated in a variety of respiratory symptoms. Eighty-two asthmatic children aged 6–16 years with doctor-diagnosed sensitization to inhalants and presenting with asthma exacerbation participated in this study of food allergies linked to asthma exacerbations. The diagnosis of food allergy was established using a questionnaire, clinical criteria, serum-specific IgE antibody measurements, and an atopy patch test. Asthma exacerbation was determined using fractional exhaled nitric oxide management after the children were admitted to the hospital. On the basis of questionnaire data, suspected food allergy was identified in 59.8% children. The positive and negative rates of serum food-specific IgE tests were 54.9% and 45.1%, respectively. The results of atopy patch tests in radioallergosorbent-positive participants were 88.9% positive and 12.5% negative. Food allergy is a risk factor for asthma exacerbation, and evaluation of food allergy in selected patients with asthma is indicated.     

Food allergy diagnostics: scientific and unproven procedures

PURPOSE OF REVIEW: The accurate diagnosis of food allergy is crucial not only for the right treatment but also for the avoidance of unnecessary diets. The diagnostic work-up of suspected food allergy includes the measurement of food-specific IgE antibodies using serologic assays, the skin prick test, elimination diets and oral provocation tests. In addition, some approaches are either under further rigorous investigation (the atopy patch test) or are already in widespread use, particularly by practitioners of alternative or complementary medicine, but are considered unproven. These diagnostic methods include specific IgG to foods, provocation/neutralization testing, kinesiology, cytotoxic tests and electrodermal testing. This review covers some of the most common scientifically validated and unproven approaches used in the diagnosis of food allergy. RECENT FINDINGS: For specific serum IgE and the SPT, decision points have been established for some foods, allowing prediction of clinical relevance. The APT may be helpful, especially when considered in combination with defined levels of specific IgE. In regard to other approaches, most scientific studies do refute the usefulness of these approaches. SUMMARY: In most patients, controlled oral food challenges remain the gold standard in the diagnostic work-up of suspected food allergy. The skin prick test and measurement of specific IgE antibodies to food extracts, individual allergens or allergenic peptides are helpful in the diagnostic approach. Food-specific IgG continues to be an unproven or experimental test. The other alternative and complementary techniques have no proven benefit and may endanger patients via misdiagnosis.     

Food protein-induced enterocolitis syndrome oral food challenge: Time for a change?

ObjectiveFood protein-induced enterocolitis syndrome (FPIES) is typically diagnosed based on a characteristic clinical history; however, an oral food challenge (OFC) may be necessary to confirm the diagnosis or evaluate for the development of tolerance. FPIES OFC methods vary globally, and there is no universally agreed upon protocol. The objective of this review is to summarize reported FPIES OFC approaches and consider unmet needs in diagnosing and managing FPIES.Data SourcesPubMed database was searched using the keywords food protein-induced enterocolitis syndrome, oral food challenge, cow milk allergy, food allergy, non-immunoglobulin E–mediated food allergy and FPIES.Study SelectionsPrimary and review articles were selected based on relevance to the diagnosis of FPIES and the FPIES OFC.ResultsWe reviewed the history of FPIES and the evolution and variations in the FPIES OFC. A summary of current literature suggests that most patients with FPIES will react with 25% to 33% of a standard serving of the challenged food, there is little benefit to offering a divided dose challenge unless there is suspicion of specific immunoglobulin E to the food being challenged, reactions typically appear within 1 to 4 hours of ingestion, and reactions during OFC rarely result in emergency department or intensive care unit admission.ConclusionInternational standardization in the FPIES OFC approach is necessary with particular attention to specific dose administration across challenged foods, timing between the patient’s reaction and offered OFC to verify tolerance, patient safety considerations before the OFC, and identification of characteristics that would indicate home reintroduction is appropriate.