Q:

4/23/2012
In the past it has been recommended that we don't do component testing for peanut allergy as we have not had enough information to state that the expense justifies its use on a regular basis. However, since there have been some additional publications now, is it something that should be done to predict response to oral challenge, etc. We just updated the expense and the test is now $300 and it is not covered by insurance. Thank you.

A:

Thank you for your inquiry.

Clearly your question is timely and pertinent. However, I cannot answer it definitively because although component testing can clearly be potentially helpful in discerning patients who are truly systemically allergic to peanuts from those, for example, who may only have oral allergy syndrome (pollen-fruit syndrome) to peanut ingestion, the decision as to the cost/benefit ratio is one that can only be made separately for each individual patient being evaluated. In addition, there are certain caveats involved regarding these tests.

First of all, you can see from the abstracts copied below that there is good evidence in the literature that component testing can be helpful as mentioned above. In addition, it appears as if in this country, Ara h 2 is perhaps the major allergen with Ara h 1 and Ara h 3 also culpable in regards to the risk for a true anaphylactic or systemic reaction. Other antigens are less likely to produce a systemic response, but can produce oral symptoms upon ingestion. Therefore, when one is faced with the question as to the distinction between the risk for only an oral versus a systemic response, component testing can clearly be of help.

The use, however, in any individual patient is dependent upon a cost/benefit analysis, and that can only be determined via a review of all the factors involved (the patient’s ability to pay, the potential severity of previous reactions if any, the presence only of oral allergy symptoms and no systemic reactions, et cetera. However, the science appears valid, and should the cost not be prohibitive, this test can be helpful in select cases.

It also should be remembered, however, that based upon literature to date (see several abstracts copied below), the universality of Ara h 1, 2, and 3 being the major allergens responsible for systemic reactions is challengeable. It appears in some geographical locations other allergens may also be responsible for systemic reactions. Therefore the ethnicity of the patient, where they were raised, and the present geographical area needs to be taken into consideration.

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

Allergy or tolerance in children sensitized to peanut: Prevalence and differentiation using component-resolved diagnostics
Journal of Allergy and Clinical Immunology, Volume 125, Issue 1, Pages 191-197.e13 2010 Abstract
Background: Not all peanut-sensitized children develop allergic reactions on exposure.
Objective: To establish by oral food challenge the proportion of children with clinical peanut allergy among those considered peanut-sensitized by using skin prick tests and/or IgE measurement, and to investigate whether component-resolved diagnostics using microarray could differentiate peanut allergy from tolerance.
Methods: Within a population-based birth cohort, we ascertained peanut sensitization by skin tests and IgE measurement at age 8 years. Among sensitized children, we determined peanut allergy versus tolerance by oral food challenges. We used open challenge among children consuming peanuts (n = 45); others underwent double-blind placebo-controlled challenge (n = 34). We compared sensitization profiles between children with peanut allergy and peanut-tolerant children by using a microarray with 12 pure components (major peanut and potentially cross-reactive components, including grass allergens).
Results: Of 933 children, 110 (11.8%) were peanut-sensitized. Nineteen were not challenged (17 no consent). Twelve with a convincing history of reactions on exposure, IgE ≥15 kUa/L and/or skin test ≥8mm were considered allergic without challenge. Of the remaining 79 children who underwent challenge, 7 had ≥2 objective signs and were designated as having peanut allergy. We estimated the prevalence of clinical peanut allergy among sensitized subjects as 22.4% (95% CI, 14.8% to 32.3%). By using component-resolved diagnostics, we detected marked differences in the pattern of component recognition between children with peanut allergy (n = 29; group enriched with 12 children with allergy) and peanut-tolerant children (n = 52). The peanut component Ara h 2 was the most important predictor of clinical allergy.
Conclusion: The majority of children considered peanut-sensitized on the basis of standard tests do not have peanut allergy. Component-resolved diagnostics may facilitate the diagnosis of peanut allergy

Nicolaos Nicolaou, MD, PhD Quantification of specific IgE to whole peanut extract and peanut components in predictionof peanut allergy letter to editor
J Allergy Clin Immunol March 2011 page 684.

Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions
The Journal of Allergy and Clinical Immunology
Volume 127, Issue 3 , Pages 603-607, March 2011
Background: Peanut allergy affects persons from various geographic regions where populations are exposed to different dietary habits and environmental pollens.
Objective: We sought to describe the clinical and immunologic characteristics of patients with peanut allergy from 3 countries (Spain, the United States, and Sweden) using a molecular component diagnostic approach.
Methods: Patients with peanut allergy from Madrid (Spain, n = 50), New York (United States, n = 30), Gothenburg, and Stockholm (both Sweden, n = 35) were enrolled. Clinical data were obtained either from a specific questionnaire or gathered from chart reviews. IgE antibodies to peanut extract and the peanut allergens rAra h 1, 2, 3, 8 and 9, as well as to cross-reactive birch (rBet v 1) and grass (rPhl p 1, 5, 7, and 12) pollen allergens, were analyzed.
Results: American patients frequently had IgE antibodies to rAra h 1 to 3 (56.7% to 90.0%) and often presented with severe symptoms. Spanish patients recognized these 3 recombinant peanut allergens less frequently (16.0% to 42.0%), were more often sensitized to the lipid transfer protein rAra h 9 (60.0%), and typically had peanut allergy after becoming allergic to other plant-derived foods. Swedish patients detected rAra h 1 to 3 more frequently than Spanish patients (37.1% to 74.3%) and had the highest sensitization rate to the Bet v 1 homologue rAra h 8 (65.7%), as well as to rBet v 1 (82.9%). Spanish and Swedish patients became allergic to peanut at 2 years or later, whereas the American children became allergic around 1 year of age.
Conclusions: Peanut allergy has different clinical and immunologic patterns in different areas of the world. Allergen component diagnostics might help us to better understand this complex entity

J Allergy Clin Immunol. 2012 Apr;129(4):1056-63. Epub 2012 Mar 3.
Dang TD, Tang M, Choo S, Licciardi PV, Koplin JJ, Martin PE, Tan T, Gurrin LC, Ponsonby AL, Tey D, Robinson M, Dharmage SC, Allen KJ; HealthNuts study.
Source
Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
Abstract
Background: Measurement of whole peanut-specific IgE (sIgE) is often used to confirm sensitization but does not reliably predict allergy. Ara h 2 is the dominant peanut allergen detected in 90% to 100% of patients with peanut allergy and could help improve diagnosis.
Objectives: We sought to determine whether Ara h 2 testing might improve the accuracy of diagnosing peanut allergy and therefore circumvent the need for an oral food challenge (OFC).
Methods: Infants from the population-based HealthNuts study underwent skin prick tests to determine peanut sensitization and subsequently underwent a peanut OFC to confirm allergy status. In a stratified random sample of 200 infants (100 with peanut allergy and 100 with peanut tolerance), whole peanut sIgE and Ara h 2 sIgE levels were quantified by using fluorescence enzyme immunoassay.
Conclusion: Ara h 2 plasma sIgE test levels provide higher diagnostic accuracy than whole peanut plasma sIgE levels and could be considered a new diagnostic tool to distinguish peanut allergy from peanut tolerance, which might reduce the need for an OFC

By using the previously published 95% positive predictive value of 15 kU(A)/L for whole peanut sIgE, a corresponding specificity of 98% (95% CI, 93% to 100%) was found in this study cohort. At the equivalent specificity of 98%, the sensitivity of Ara h 2 sIgE is 60% (95% CI, 50% to 70%), correctly identifying 60% of subjects with true peanut allergy compared with only 26% correctly identified by using whole peanut sIgE. We report that when using a combined approach of plasma sIgE testing for whole peanut followed by Ara h 2 for the diagnosis of peanut allergy, the number of OFCs required is reduced by almost two thirds.Increasing the accuracy of peanut allergy diagnosis by using Ara h 2.

Int Arch Allergy Immunol. 2011;156(3):231-3. Epub 2011 Jun 29.
Component-resolved diagnostics: shedding light on the so-called 'squishy science' of food allergies?
Kim JS, Nowak-Węgrzyn A.
Int Arch Allergy Immunol. 2011;156(3):282-90. Epub 2011 Jun 29.
Evaluation of IgE antibodies to recombinant peanut allergens in patients with reported reactions to peanut.
Movérare R, Ahlstedt S, Bengtsson U, Borres MP, van Hage M, Poorafshar M, Sjölander S, Akerström J, van Odijk J.
Source
Phadia AB, Uppsala University, Uppsala, Sweden.
Abstract
Background: Peanut may cause severe reactions in allergic individuals. The objective was to evaluate IgE antibodies to various recombinant (r) peanut and birch pollen allergens in relation to IgE levels to whole peanut extract and severe allergic reactions to peanut.
Methods: Seventy-four Swedish peanut-allergic patients (age: 14-61 years) reported previous peanut exposure and associated symptoms using a questionnaire. Their IgE reactivity to peanut, birch pollen and individual allergen components was analyzed using ImmunoCAP.
Results: Of the 48 subjects sensitized to Ara h 1, 2 or 3, 60% had peanut-specific IgE levels >15 kU(A)/l, while 100% of the subjects without detectable IgE to these allergens had low peanut-specific IgE levels (<10 kU(A)/l). The levels of IgE to rAra h 8, rBet v 1 and birch pollen were highly correlated (r(S) = 0.94, p < 0.0001). Fifty-eight patients reported adverse reactions after accidental or deliberate peanut exposure (oral, inhalation or skin) of whom 41 had IgE to rAra h 1, 2 or 3. Symptoms of respiratory distress were associated with sensitization to Ara h 1, 2 or 3 (56 vs. 18%, p < 0.01). Two cases of anaphylaxis were reported among the individuals sensitized to Ara h 1-3. IgE to rAra h 8, rAra h 9, profilin or cross-reactive carbohydrate determinants were not associated with severe symptoms.
Conclusions: The results indicate that IgE reactivity to Ara h 1, 2 and 3 is associated with severe reactions after exposure to peanut in Swedish patients.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology