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

doi:10.1067/mai.2001.114708

Journal of Allergy and Clinical Immunology

Volume 107, Issue 5, May 2001, Pages 891-896

https://doi.org/10.1067/mai.2001.114708 Get rights and content

Abstract

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. (J Allergy Clin Immunol 2001;107:891-6.)

Section snippets

Study population

One hundred consecutive children and adolescents referred to the Johns Hopkins Pediatric Allergy Clinic for evaluation of suspected IgE-mediated food hypersensitivity were enrolled in the study. Patients ranged in age from 3 months to 14 years (median, 3.8 years), and the majority were boys (male/female = 62:38). Sixty-one percent of patients had atopic dermatitis, approximately one half had asthma, and about 90% came from atopic families. Evaluation consisted of an extensive history, physical

Results

One hundred children and adolescents with suspected food allergy were enrolled in the study. The diagnosis of food hypersensitivity was based on the outcome of DBPCFCs, a convincing history of clinical reactivity, or a suggestive history of reactivity with a food-specific IgE level that exceeded the previously established 95% decision points. As shown in Table I, the prevalence rates of allergic reactivity to individual foods in the prospective study compared with prevalence rates in the

Discussion

A number of studies have confirmed the poor positive predictive value of patient history and skin prick test and RAST results in the diagnosis of symptomatic IgEmediated food hypersensitivity.2, 12, 15, 17, 18 However, a number of studies have confirmed that negative skin prick test responses have excellent negative predictive values for excluding the presence of IgE-mediated food allergy.11, 14, 17 Consequently, the DBPCFC has become the gold standard for the diagnosis of food allergy, with

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Pediatric oral food challenges in the outpatient setting: A single-center experience
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Oral food challenge (OFC) is the criterion standard for diagnosing food allergy (FA). It is important to have parameters to aid in selecting ideal OFC candidates.
We sought to characterize outcomes and predictors of OFCs for common food allergens.
We completed a retrospective chart review of all OFCs for IgE-mediated FA performed at Duke University pediatric allergy clinics from June 2017 through May 2022. Patients were deemed eligible for milk, egg, and nut OFC if testing revealed a specific IgE level not exceeding 2 kU/L and a skin prick test (SPT) resulting in a wheal size not exceeding 5 mm. Different parameters were followed for selecting candidates for baked challenge.
A total of 663 OFCs were conducted on 510 patients (59% male). The most common foods challenged were peanut (26%), plain egg (23%), baked egg (8%), and milk (8%), with pass rates of 84%, 88%, 62%, and 84%, respectively. Of the patients who failed OFC, 84% had objective symptoms, 23% had multisystemic reactions, and 15% required epinephrine. Although the presence of a personal or family history of atopy or prior failed OFC was not associated with outcomes, a history of anaphylaxis (regardless of the trigger) was associated with increased risk of failure.
Although there are no established consensus guidelines, our study provides a benchmark illustrating that cutoffs of a specific IgE level not exceeding 2 kU/L and SPT finding not exceeding 5 mm result in a failure rate of approximately 13% for nonbaked milk, nonbaked egg, and nuts. The high rate of failed baked egg OFCs is likely related to selection bias, but our results illustrate the low negative predictive value of ovomucoid.
NOVEOS and ImmunoCAP Have Similar Performances for Diagnosing Food Allergies
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The clinical significance of newly available platforms for specific IgE measurement must be evaluated. However, data are lacking for NOVEOS (Hycor), especially for food allergens.
We compared the technical and clinical performance of two platforms (ImmunoCAP and NOVEOS) to measure specific IgE to 10 food allergens.
Sera from 289 clinically characterized patients were tested for IgE specific for six food allergen extracts (egg white, cow’s milk, peanut, hazelnut, fish, and shrimp) and four molecular allergens (Gal d 1, Bos d 8, Ara h 2, and Cor a 14). Specific IgE measurements were carried out using ImmunoCAP and NOVEOS methods. Food allergy diagnoses were established according to international guidelines.
A strong correlation (ρ > 0.9) was present between the two platforms whereas specific IgE concentrations measured with NOVEOS were consistently lower (mean, –15%) than with ImmunoCAP. NOVEOS and ImmunoCAP provided similar overall odds ratios and relative risks for food allergy diagnosis with both allergen extracts and molecular allergens. When all 10 allergens were considered, NOVEOS provided better receiver operating characteristic curves (P = .04). Finally, we found that the most discordant results were observed with hazelnut and peanut extracts and were related to cross-reactive carbohydrate determinants for these two with ImmunoCAP.
Specific IgE determination by either ImmunoCAP or NOVEOS (odds ratios of allergy, 25.1 or 33.0, respectively) is highly informative regarding the risk of allergy in the selected population. The NOVEOS platform presents the advantage of being less affected by unwanted reactivity owing to carbohydrate determinant-specific IgE while requiring a 10-fold lower test sample volume.
Epitope-Based IgE Assays and Their Role in Providing Diagnosis and Prognosis of Food Allergy
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With advances in molecular and computational science, epitope-specific IgE antibody profiling has been developed and recently brought into clinical practice. Epitope-based testing detects IgE antibodies that directly bind to antigenic sites of an allergen, providing increased resolution specificity and fewer false-positive results for diagnosing food allergy. Epitope-binding profiles may also serve as prognostic markers of food allergy and help predict quantities of allergen that would provoke a reaction (ie, eliciting dose, possible severity of a reaction after allergen ingestion, and outcomes of treatment options such as oral immunotherapy [OIT]). Future studies are under way to discover additional applications of epitope-specific antibodies for multiple food allergens.
The Value of Current Laboratory Tests in Diagnosing Food, Venom, and Drug Allergies
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An accurate diagnosis of IgE-mediated allergies is necessary to inform risk management for severe allergic reactions including anaphylaxis for food, venom, and drug allergies. The most widely available laboratory test for allergy is serum-specific IgE testing, which is routinely used for food allergy and insect sting allergy. Testing for specific IgE is limited by high sensitivity and low specificity, resulting in concern regarding overdiagnosis. Testing of allergen components has led to improved diagnosis for some food and venom allergens. Additional options for laboratory tests, such as epitope analysis, basophil activation, and mast cell activation, are being investigated for their potential to optimize diagnosis and provide predictors for reaction severity and treatment response. In contrast, laboratory testing for drug allergy is more limited because to date, there are no well-validated commercial assays in the United States. Furthermore, it is important to diagnose delayed reactions to medications, because these also significantly affect decision-making regarding therapeutic options for infectious disorders. Reliable tests for both immediate and delayed drug hypersensitivity are much needed, because drug allergy labels can significantly limit treatment options for patients. Research in this area is emerging.
History and Utility of Specific IgE Cutoff Levels: What is the Relevance for Allergy Diagnosis?
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Allergy is defined clinically, by symptoms on allergen exposure. A patient is considered sensitized when allergen-specific IgE (sIgE) antibody can be detected in serum or plasma or a skin test result is positive, even if no clinical reaction has been experienced. Sensitization should be regarded as a requisite and risk factor for allergy but is not synonymous with an allergy diagnosis. To provide a correct allergy diagnosis, test results regarding allergen-sIgE must always be considered in view of the patient’s case history and clinical observations. Correct assessment of a patient’s sensitization to specific allergens relies on the use of accurate and quantitative methods for detection of sIgE antibodies. The evolution of sIgE immunoassays toward higher analytical performance and the use of different cutoff levels in the interpretation of test results sometimes cause confusion. Earlier versions of sIgE assays offered a limit of quantitation of 0.35 kilounits of sIgE per liter (kU_A/L), which also became an established cutoff level for a positive test result in the clinical use of the assays. Current sIgE assays are capable of reliably measuring sIgE levels as low as 0.1 kU_A/L and can thereby demonstrate sensitization in cases in which previous assays could not. When the outcome of sIgE test results is evaluated, it is critically important to distinguish between the analytical data as such and their clinical interpretation. Even though sIgE may be present in the absence of symptoms of allergy, available information suggests that sIgE concentrations between 0.1 kU_A/L and 0.35 kU_A/L may be clinically relevant in some individuals, not least among children, although this should be further evaluated for various allergies. Moreover, it is becoming widely adopted that nondichotomous interpretation of sIgE levels may offer a diagnostic benefit compared with using a predefined cutoff level.
Safety of Multifood Oral Immunotherapy in Children Aged 1 to 18 Years at an Academic Pediatric Clinic
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Oral immunotherapy (OIT) aims to increase the reaction threshold to a food allergen and decrease the risk of a potentially life-threatening allergic reaction in the event of an accidental ingestion. Whereas single-food OIT is the most extensively studied, data on multifood OIT are limited.
Our study aimed to examine the safety and feasibility of single-food and multifood immunotherapy in a large cohort in an outpatient pediatric allergy clinic setting.
A retrospective review of patients enrolled in single-food and multifood OIT between September 1, 2019, and September 30, 2020, and data collection of those patients until November 19, 2021, were performed.
There were 151 patients who underwent either an initial dose escalation (IDE) or a standard oral food challenge. Seventy-eight patients were receiving single-food OIT with 67.9% reaching maintenance. Fifty patients were undergoing multifood OIT with 86% reaching maintenance to at least 1 OIT food and 68% reaching maintenance for all their foods. Of the 229 IDEs, there were low frequencies of failed IDEs (10.9%), epinephrine administration (8.7%), emergency department referrals (0.4%), and hospital admission (0.4%). Cashew accounted for one-third of failed IDEs. Epinephrine administration during home dosing occurred in 8.6% of patients. Eleven patients discontinued OIT owing to symptoms during up-dosing. No patients discontinued once reaching maintenance.
Desensitization to 1 food or multiple foods simultaneously through OIT appears to be safe and feasible using the OIT protocol that has been established. The most common adverse reaction causing discontinuation of OIT was gastrointestinal symptoms.

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^☆: Supported in part by a grants from Pharmacia/Upjohn Diagnostics, the National Institutes of Health Division of Research Resources grant MO1 RR00052, and the National Institute of Allergy & Infectious Disease, National Institutes of Health grant AI-24439.

^☆☆: Reprint requests: Hugh A. Sampson, MD, Department of Pediatrics; Box 1090, The Jaffe Institute of Food Allergy, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574.

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Food and Drug Reactions and AnaphylaxisUtility of food-specific IgE concentrations in predicting symptomatic food allergy☆,☆☆

Abstract

Section snippets

Study population

Results

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Pediatr

J Allergy Clin Immunol

A prospective study of cow milk allergy in Danish infants during the first 3 years of life

Allergy

Prospective appraisal of complaints of adverse reactions to foods in children during the first 3 years of life

Pediatrics

Food and Drug Reactions and Anaphylaxis
Utility of food-specific IgE concentrations in predicting symptomatic food allergy☆,☆☆