Q:

What is the false positive rate of RAST testing for peanut?

Is there a specific RAST level that you would avoid subsequent skin prick testing?
I have a 2 year old child that developed redness around the mouth and on the face immediately after eating peanut, which then self-resolved. He had a RAST level 2 to peanut. Would you consider skin testing for this patient?
When would you absolutely not skin test out of concern for an adverse event from the skin prick test itself?

A:

Thank you for your recent inquiry.

Copied below are three abstracts which relate to the question you pose. One of these discusses in vitro assays for serum-specific IgE. The term "RAST" is no longer applicable. It refers to a technique employing radioactivity to measure serum-specific IgE. New techniques do not employ radioactivity, and therefore this generic term cannot be applied to the measurement of serum-specific IgE to allergens. The answer below is assuming you employed the immunocap test for reasons noted below.

As you can see from reading these abstracts, the tests for serum-specific IgE do not correlate as well as we would like. Most of the studies defining "false-positive" and "false-negative" levels of serum-specific IgE have been done for the ImmunoCap assay. Therefore we are limiting our comments to your inquiry to the ImmunoCap.

In this regard, the other two abstracts copied below are referring to the use of ImmunoCap to correctly identify clinically significant levels of serum-specific IgE that would correlate with the ingestion of the allergen in question.

There are several points to be gleaned from these abstracts. First, a reaction to the ingestion of a food and the level of serum-specific IgE detected by ImmunoCap is a linear relationship. There is no completely trustworthy cut-off level at which point a reaction to the ingestion of the food can be guaranteed to be negative or positive. The same would be true regarding the relationship between the immunpcap and the skin test. However, if the level of serum-specific IgE is 15 kUa/L, it is highly likely that a reaction will occur upon the ingestion of peanut. There is no low level which guarantees no reaction, but reactions become far less likely if the level is less than 2 kUa/L. Nonetheless, reactions can occur with a negative ImmunoCap result.

From these studies you can see that an ImmunoCap of less than 2 kUa/L would indicate that this child has a good chance of being able to tolerate peanut ingestion, but certainly does not guarantee this. Since you did not state the specific test that you utilized to detect serum-specific IgE, of course, I cannot tell whether the level of "2" you described would give you any such reassurance.

I would have no problem skin testing this child. I have not yet seen a patient that I would "absolutely not skin test out of concern for an adverse event from the skin prick test itself." It is true that anaphylactic episodes have occurred to skin testing, but they are quite rare.

In the final analysis, the only true test of whether or not a child can ingest a food safely is an oral challenge. The in vitro test coupled with the clinical interpretation of the history simply serve as guidelines as to when it may be safe to perform an oral challenge. There is no specific in vitro serum IgE that would indicate a skin test would not be safe. In addition, there is no specific level that would guarantee the safety of ingestion or predict a positive reaction upon ingestion. The levels cited above offer some reassurance, but no guarantee.

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

The Journal of Allergy and Clinical Immunology
Volume 122 1, Issue , Pages 145-151, July 2008
Objectives: The purpose of this study was to determine the utility of food-specific IgE measurements for identifying symptomatic peanut, tree nut, and seed allergies and to augment what is known about the relationships among these foods.
Methods: Patients referred for suspected peanut or tree nut allergies answered a questionnaire about their perceived food allergies. Allergen-specific diagnoses were based on questionnaire, medical history, and, when relevant, skin prick tests and serum specific IgE levels. Sera from the patients were analyzed for specific IgE antibodies to peanuts, tree nuts, and seeds by using ImmunoCAP Specific IgE (Phadia, Inc, Uppsala, Sweden).
Results: Three hundred twenty-four patients (61% male; median age, 6.1 years; range, 0.2-40.2 years) were evaluated. The patients were highly atopic (57% with atopic dermatitis and 58% with asthma). The majority of patients with peanut allergy were sensitized to tree nuts (86%), and 34% had documented clinical allergy. The relationship between diagnosis and allergen-specific IgE levels were estimated by using logistic regression. Diagnostic decision points are suggested for peanut and walnut. Probability curves were drawn for peanut, sesame, and several tree nuts. High correlations were found between cashew and pistachio and between pecan and walnut.
Conclusions: Quantification of food-specific IgE is a valuable tool that will aid in the diagnosis of symptomatic food allergy and might decrease the need for double-blind, placebo-controlled food challenges.

Journal of Allergy and Clinical Immunology Vol. 121, Issue 5, Pages 1219-1224
Background: In vitro testing is commonly used to diagnose and manage allergies. Clinical reactivity has been correlated with food-specific IgE levels by using theImmunoCAP (Phadia, Uppsala, Sweden).
Objective: To determine whether IgE levels derived from different assays are equivalent to those measured by ImmunoCAP.
Methods: Fifty patients from the Mount Sinai Pediatric Allergy practice were prospectively enrolled. For each deidentified sample, specific IgE levels were measured to egg, milk, peanut, cat, birch, and Dermatophagoides farinae at different laboratories, each using a different assay system (PhadiaImmunoCAP, Agilent Turbo-MP, and Siemens Immulite 2000). Results were analyzed to determine whether IgE measurements were equivalent. Food allergen–specific IgE levels were correlated with clinical data and around empirically determined thresholds that predict probability of clinical disease in 50% or 95% of subjects.
Results: Variable degrees of agreement existed among the 3 assays. Immulite 2000 overestimated all specific IgE levels compared with ImmunoCAP. Turbo-MP overestimated for egg but underestimated for birch and D farinae. Differences for milk, peanut, and cat were observed, without a trend toward overestimation or underestimation. Furthermore, several values for the food allergens were discrepant around the 50% and 95% positive predictive values for clinical reactivity.
Conclusion: Discrepancies in specific IgE values from 3 different assays can potentially lead to altered management and treatment. The predictive values for clinical reactivity associated with food-specific IgE levels determined by ImmunoCAP should not be applied to results from other assays.

The Journal of Allergy and Clinical Immunology
Volume 100, Issue 4 , Pages 444-451, October 1997
Background: The double-blind, placebo-controlled food challenge (DBPCFC) is the “gold standard” for diagnosis of food hypersensitivity. Skin prick tests and RASTs are sensitive indicators of food-specific IgE antibodies but poor predictors of clinical reactivity. Previous studies suggested that high concentrations of food-specific IgE antibody were predictive of food-induced clinical symptoms. Because the CAP System FEIA (Pharmacia Diagnostics, Uppsala, Sweden) provides a quantitative assessment of allergen-specific IgE antibody, this study was undertaken to determine the potential utility of the CAP System FEIA in diagnosis of IgE-mediated food hypersensitivity. Methods: Sera from 196 patients with food allergy were analyzed for specific IgE antibodies to egg, milk, peanut, soy, wheat, and fish by CAP System FEIA. Sera were randomly selected from 300 stored samples of children and adolescents who had been evaluated by history, skin prick tests, and DBPCFCs. The study population was highly atopic; all patients had atopic dermatitis, and approximately 50% had asthma and allergic rhinitis at the time of initial evaluation. The performance characteristics of the CAP System FEIA were compared with those of skin prick tests and the outcome of DBPCFCs or “convincing” histories of anaphylactic reactions. Results: The prevalence of specific food allergies in the study population varied from 22% for wheat to 73% for egg. Allergy to egg, milk, peanut, and soy accounted for 87% of confirmed reactions. The performance characteristics of skin prick tests and CAP System FEIA (egg, milk, peanut, fish) were comparable, with excellent sensitivity and negative predictive accuracy but poor specificity and positive predictive accuracy. The performance characteristics of the CAP System FEIA for soy and wheat were poor. For egg, milk, peanut, and fish allergy, diagnostic levels of IgE, which could predict clinical reactivity in this population with greater than 95% certainty, were identified: egg, 6 kilounits of allergen-specific IgE per liter (kUA/L); milk, 32 kUA/L; peanut, 15 kUA/L; and fish, 20 kUA/L. Conclusions: When compared with the outcome of DBPCFCs, results of CAP System FEIA are generally comparable to those of skin prick tests in predicting symptomatic food hypersensitivity. Furthermore, by measuring the concentrations of food-specific IgE antibodies with the CAP System FEIA, it is possible to identify a subset of patients who are highly likely (>95%) to experience clinical reactions to egg, milk, peanut, or fish. This could eliminate the need to perform DBPCFCs in a significant number of patients suspected of having IgE-mediated food allergy. (J Allergy Clin Immunol 1997;100:444-51).

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology