1) Any additional recommendations regarding the use of component testing in peanut allergy from last year’s response (4/12)?

2) What is the current thinking regarding the early introduction of peanut into the diet of an infant to induce oral tolerance?


Thank you for your inquiry.

Both topics you mentioned are complex and open to some interpretation and sometimes, in regards to the second topic, controversy. Neither allows for a brief summary, and a comprehensive discussion of the issues involved go far beyond the scope of our website. So, the best we could do would be to refer you to a few readily accessible articles which discuss these issues in detail, and will supply you with the latest information of which I am aware in regards to each.

There are three abstracts of articles copied below that deal with component testing, and two abstracts that deal with the role of early introduction of food into the diet as a preventive technique. The article entitled "The Utility of Peanut Components in the Diagnosis of IgE-Mediated Peanut Allergy Among Distinct Populations" I think will be the most helpful to you in regards to component testing. The other two will also be very helpful.

There are two references regarding the role of early introduction of foods into the diet, and they, too, will offer you the latest thoughts regarding this topic.

Thank you again for your inquiry and we hope this response is helpful to you.

J Allergy Clin Immunol Pract. 2013 Jan;1(1):75-82. doi: 10.1016/j.jaip.2012.11.002. Epub 2012 Dec 27.
The Utility of Peanut Components in the Diagnosis of IgE-Mediated Peanut Allergy Among Distinct Populations.
Lieberman JA, Glaumann S, Batelson S, Borres MP, Sampson HA, Nilsson C.
Author information
Elliot and Roslyn Jaffe Food Allergy Institute, Division of Allergy and Immunology, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY.
Background: Increasing data suggest that analysis of IgE to peanut components can be clinically helpful and possibly more accurate than IgE to whole peanut. Not all studies examining this topic, however, have used prospective samples, multiple components, and peanut challenges.
Objective: We sought to determine the utility of peanut component testing, using a standardized, commercially available test done before oral peanut challenge in various populations of patients with suspected peanut allergy from 2 different countries.
Methods: IgE to whole peanut and the recombinant allergen components Ara h 1, 2, 3, and 8 were analyzed from serum samples drawn before double-blind peanut challenge from 4 distinct cohorts of patients with suspected peanut allergy from 2 nations (United States and Sweden).
Results: Patients (n = 167; median age, 11.7 years; interquartile range, 7.0-15.0 years) had serum analyzed for peanut components and completed an oral food challenge to peanut. Although IgE to peanut was the most sensitive test (0.93), Ara h 2 was the most specific (0.92) and provided the best positive predictive value (0.94) of all the tests. Ara h 2 was also the best overall diagnostic test by receiver operating characteristic analysis (area under the curve, 0.84; P < .05).
Conclusions: In patients with suspected peanut allergy, IgE to peanut is a sensitive test but is not specific. IgE to Ara h 2 is a more specific and more accurate diagnostic test in this sampling of patients with suspected peanut allergy. Given each tests attributes, a stepwise approach to testing may provide clinicians with a way to minimize the need for peanut challenges.

Clin Exp Allergy. 2013 Aug;43(8):967-74. doi: 10.1111/cea.12136.
IgE binding to peanut components by four different techniques: Ara h 2 is the most relevant in peanut allergic children and adults.
Klemans RJ, Liu X, Knulst AC, Knol MJ, Gmelig-Meyling F, Borst E, Pasmans SG, Knol EF.
Author information
Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
Background: Several studies have analysed the diagnostic value of specific IgE (sIgE) for individual peanut allergens. However, little is known about the concordance between different techniques available in both children and adults.
Objective: To evaluate the value of individual peanut allergens by different techniques, i.e. multi-plexed microarray, single-plexed IgE assay, skin prick test (SPT) and immunoblot in both peanut allergic adults and children.
Methods: Sensitization patterns to peanut allergens Ara h 1, 2, 3, and 8 were evaluated using four different techniques: multi-plexed microarray immunoassay, single-plexed IgE assay, SPT and immunoblot. Twenty-two peanut allergic adults and 15 children scored on clinical severity according to double-blind, placebo-controlled food challenges and 27 atopic control patients were included.
Results: Comparable sensitivity values were found between all four techniques in adults, with the highest sensitivity for Ara h 2 (76.2-95.5%, compared to 100% with all techniques in children). The multi-plexed assay to Ara h 1 (93.3%) demonstrated a higher sensitivity compared with the other three techniques (P = 0.04) in children, but absolute values were perfectly correlated. There were no differences between adults and children. The area under the receiver operating characteristic curve (AUC) of sIgE to Ara h 1 was higher with the multi-plexed assay compared with the single-plexed assay (0.91 vs. 0.75). In adults, sIgE to Ara h 1, 2, and 3 was correlated with clinical severity. No such correlation was found in children.
Conclusion and Clinical Relevance: In conclusion, the single- and multi-plexed assay, SPT and immunoblot perform equally in both peanut allergic adults and children, with Ara h 2 being most often recognized with all techniques. Specific IgE to Ara h 1, 2, and 3 in adults was correlated with severity.

J Allergy Clin Immunol. 2013 Jan;131(1):157-63. doi: 10.1016/j.jaci.2012.08.010. Epub 2012 Sep 29.
The diagnostic value of specific IgE to Ara h 2 to predict peanut allergy in children is comparable to a validated and updated diagnostic prediction model.
Klemans RJ, Otte D, Knol M, Knol EF, Meijer Y, Gmelig-Meyling FH, Bruijnzeel-Koomen CA, Knulst AC, Pasmans SG.
Author information
Department of (Paediatric) Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
Background: A diagnostic prediction model for peanut allergy in children was recently published, using 6 predictors: sex, age, history, skin prick test, peanut specific immunoglobulin E (sIgE), and total IgE minus peanut sIgE.
Objectives: To validate this model and update it by adding allergic rhinitis, atopic dermatitis, and sIgE to peanut components Ara h 1, 2, 3, and 8 as candidate predictors. To develop a new model based only on sIgE to peanut components.
Methods: Validation was performed by testing discrimination (diagnostic value) with an area under the receiver operating characteristic curve and calibration (agreement between predicted and observed frequencies of peanut allergy) with the Hosmer-Lemeshow test and a calibration plot. The performance of the (updated) models was similarly analyzed.
Results: Validation of the model in 100 patients showed good discrimination (88%) but poor calibration (P < .001). In the updating process, age, history, and additional candidate predictors did not significantly increase discrimination, being 94%, and leaving only 4 predictors of the original model: sex, skin prick test, peanut sIgE, and total IgE minus sIgE. When building a model with sIgE to peanut components, Ara h 2 was the only predictor, with a discriminative ability of 90%. Cutoff values with 100% positive and negative predictive values could be calculated for both the updated model and sIgE to Ara h 2. In this way, the outcome of the food challenge could be predicted with 100% accuracy in 59% (updated model) and 50% (Ara h 2) of the patients.
Conclusions: Discrimination of the validated model was good; however, calibration was poor. The discriminative ability of Ara h 2 was almost comparable to that of the updated model, containing 4 predictors. With both models, the need for peanut challenges could be reduced by at least 50%.

Curr Opin Allergy Clin Immunol. 2010 Jun;10(3):258-66. doi: 10.1097/ACI.0b013e328339ab25.
Avoidance or exposure to foods in prevention and treatment of food allergy?
Prescott SL, Bouygue GR, Videky D, Fiocchi A.
Author information
School of Paediatrics and Child Health Research, University of Western Australia, Perth, Western Australia, Australia.
Purpose of Review: To caution against premature proposals advocating change before epidemiological and clinical evidence warrants such a paradigm shift.
Recent Findings: Until 2007, all allergy societies advocated allergen avoidance for prevention and therapy in food allergy. Since then, new evidence has prompted careful re-evaluation of the literature. In primary prevention, delayed introduction of allergenic foods to prevent food allergy was removed from most recommendations. However, there is currently no evidence that allergenic foods ought to be introduced earlier than is recommended for complementary foods, at 4-6 months of age. Here we uphold the view against an emerging school of thought that early and deliberate exposure to allergenic foods may prevent or delay the onset food allergy. While notions of promoting early oral tolerance may have some merit in theory, in practice research remains inconclusive. Of recent development are treatment advances as regards established food allergy, using food allergens to induce tolerance in highly selected populations of allergic children. However, the investigators themselves strongly warn of significant risks and stress the need to optimize safety and understand longer-term implications before these trials can be applied to routine clinical practice. In this paper we endorse the current recommendation that children with confirmed food allergy should avoid foods implicated in immediate reactions.
Summary: It is currently inappropriate and potentially dangerous to advocate deliberate exposure to foods involved in serious reactions against current recommendations and particularly so among food allergic children until more basic and clinical research become available.

Curr Opin Allergy Clin Immunol. 2010 Jun;10(3):252-7. doi: 10.1097/ACI.0b013e328337bd3a.
Should avoidance of foods be strict in prevention and treatment of food allergy?
Kim JS, Sicherer S.
Author information
Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Purpose of Review: To discuss whether strict allergen avoidance is the most appropriate strategy for managing or preventing food allergy.
Recent Findings: The standard of care for the management of food allergy has been strict allergen avoidance. This advice is based upon the suppositions that exposure could result in allergic reactions and avoidance may speed recovery. Recent studies challenge these assumptions. Studies now demonstrate that most children with milk and egg allergy tolerate extensively heated forms of these foods. Moreover, clinical trials of oral immunotherapy show that oral exposure can lead to desensitization. Additionally, recent epidemiologic studies fail to support the notion that delaying introduction of highly allergenic foods to infants and young children prevents the development of food allergy. In fact, the data suggest that delays may increase risks.
Summary: Recent data indicate that strict allergen avoidance is not always necessary for treatment, exposure may be therapeutic, and extended delay in introduction of food allergens to the diet of young children may increase allergy risks. However, in many circumstances strict avoidance is clearly necessary for treatment. Additional studies are needed to determine the risks and benefits of exposure to tolerated allergen, including identification of biomarkers to identify patients who may benefit.

Phil Lieberman, M.D.

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