Answer:
I had some difficulty with the use of the pronoun “she” as I may have misinterpreted as referring to the 4 year-old patient and some of the information may have been related to the 4 year-old’s mother. If I misinterpreted, I apologize.
As I understand the situation, your patient has a positive prick skin test to green pea and peanut, a negative in vitro component test to peanut and a history of a reaction to ingestion of green pea but no ingestion history with respect to peanut. There is a past history of a positive test to soy and egg but no allergic symptoms with ingestion.
The degree of cross reactivity between peanut and green pea is documented, but I would have expected a positive in vitro test to peanut vicillin (Ara h 1) [1]]. I am not convinced that the child is clinically sensitive to peanut but a challenge would be required to prove. I think the next course of action would be predicated on the patient’s mother’s concerns. Is she comfortable with not knowing for sure and avoiding peanut or would she be more comfortable knowing there was no risk with peanut. I generally delay open challenges with foods with a tendency for more severe allergy until the child is able to communicate symptoms. I would assume this 4 year old could do so; therefore, one option would be an open, progressive challenge to peanut, continued avoidance of green pea and an epinephrine autoinjector. There is high likelihood of a failing a peanut challenge with a wheal response to prick testing of greater than 6-8 mm (2,3,4,5). I would feel comfortable with an open challenge in a clinic prepared and equipped to treat anaphylaxis, although a double-blind, placebo controlled challenge would be more definitive. It is also reasonable to delay the challenge and repeat the prick test with specific IgE testing before making the decision to challenge. Ultimately I would also consider challenging with green pea, but I would delay for the near future and continue to avoid.
I will share your question with a veritable international food allergy expert, Dr. Wesley Burks. I will provide his response when available.
1. Wensing, Marjolein, et al. "Patients with anaphylaxis to pea can have peanut allergy caused by cross-reactive IgE to vicilin (Ara h 1)." Journal of Allergy and Clinical Immunology 111.2 (2003): 420-424.
Abstract
Background: Serologic cross-reactivity among legumes has been described; however, it is rarely clinically significant. In this study 3 patients with a history of anaphylaxis to pea are described who subsequently had symptoms after ingestion of peanut.
Objective: We investigated whether the peanut-related symptoms were due to cross-reactivity between pea and peanut proteins.
Methods: Peanut-related symptoms were documented according to case history or double-blind, placebo-controlled food challenge results. Skin prick tests were performed, and specific IgE levels were determined for pea and peanut with the CAP system FEIA. IgE-binding proteins in pea and peanut were identified by using immunoblot analysis. Cross-reactivity was studied by means of immunoblot and ELISA inhibition studies with whole extracts and purified allergens.
Results: Peanut-related symptoms consisted of oral symptoms in all patients, with additional urticaria and dyspnea or angioedema in 2 patients. All patients had a positive skin prick test response and an increased IgE level to pea and peanut. Immunoblotting revealed strong IgE binding to mainly vicilin in pea extract and exclusively to Ara h 1 in crude peanut extract. Immunoblot and ELISA inhibition studies with crude extracts, as well as purified proteins, showed that IgE binding to peanut could be inhibited by pea but not or only partially the other way around.
Conclusion: Clinically relevant cross-reactivity between pea and peanut does occur. Vicilin homologues in pea and peanut (Ara h 1) are the molecular basis for this cross-reactivity. (J Allergy Clin Immunol 2003;111:420-4.)
2. Hill, David J., Ralf G. Heine, and Clifford S. Hosking. "The diagnostic value of skin prick testing in children with food allergy." Pediatric allergy and immunology15.5 (2004): 435-441.
The diagnostic accuracy of the skin prick test (SPT) in food allergy is controversial. We have developed diagnostic cut-off levels for SPT in children with allergy to cow milk, egg and peanut. Based on 555 open food challenges in 467 children (median age 3.0 yr) we defined food-specific SPT weal diameters that were ‘100% diagnostic’ for allergy to cow milk (=8 mm), egg (=7 mm) and peanut (=8 mm). In children <2 yr of age, the corresponding weal diameters were =6 mm, =5 mm and =4 mm, respectively. These SPT cut-off levels were prospectively validated in 90 consecutive children =2 yr with challenge-proven food allergy. In young infants under 6 months of age who have not previously been exposed to a particular food item, the SPT were often negative or below the diagnostic cut-off but reached the diagnostic cut-off at the time of challenge in the second year of life. We assessed the diagnostic agreement between food-specific immunoglobulin E (IgE) antibody levels and SPT in a cohort of 820 infants and children under 2 yr of age (median age 13.1 months) with suspected allergy to cow milk, egg or peanut. When applying published 95%-positive predictive CAP values, the diagnostic accuracy of SPT and IgE antibody levels was similar for cow milk, but SPT was more sensitive in diagnosing allergy to egg (p < 0.0001) and peanut (p < 0.0001). Further studies are required to define age-specific diagnostic IgE antibody and SPT cut-off levels use in infants under 2 yr of age with suspected food allergies.
3. Van Ree, R., et al. "Profilin is a cross-reactive allergen in pollen and vegetable foods." International archives of allergy and immunology 98.2 (1992): 97-104.
Abstract
Background: Peanuts and soybeans are the major legumes involved in human food allergy; however, scarce data exist on adverse reactions to other temperate legumes, such as lentils.
Objective: The purpose of this study was to identify patients who are allergic to lentils, to assess clinical features and other associated food allergies, and to characterize allergens in lentil extract.
Methods: Twenty-two children each with a history of adverse reactions to lentils were enrolled in the study. The diagnosis of lentil allergy was based on food challenges or a convincing history of anaphylaxis, with positive skin tests and/or specific serum IgE to lentils. Lentil components were characterized by SDS-PAGE immunoblotting.
Results: Twenty of 22 subjects had symptomatic allergy to lentils at the diagnostic time. The most frequent symptoms were oropharyngeal symptoms (40%) and acute urticaria (30%); 3 patients also reported symptoms when they were exposed to steam from cooked lentils. In 18 patients, symptoms after lentil ingestion started under 4 years of age (median, 2.7 years). Nine patients had allergic reactions to other legumes: chick peas (6 patients), peas (2 patients), and green beans (1 patient). Immunoblotting patterns obtained with patients’ sera showed IgE-binding bands ranging from 14 to 84 kd. Five sera recognized 9 or more IgE-binding bands, and more than 50% of patients who were tested have specific IgE antibodies to 7 components in lentil extract.
Conclusion: Allergic reactions to lentils started early in life, usually below 4 years of age; oropharyngeal symptoms and acute urticaria were the most common symptoms through ingestion, and symptomatic reactivity to chick peas is frequently associated. (J Allergy Clin Immunol 1999;103:154-8.)
4. Roberts, Graham, and Gideon Lack. "Diagnosing peanut allergy with skin prick and specific IgE testing." Journal of allergy and clinical immunology 115.6 (2005): 1291-1296.
Background: Food allergy is common in childhood. It has been suggested that the magnitude of a skin prick test or specific IgE result can improve diagnostic usefulness, but this has been addressed in only a few tertiary challenge-based studies.
Objective: To determine the predictive value of a wheal = 8 mm or serum specific IgE = 15 kUA/L for clinical allergy and investigate whether results are generalizable.
Methods: All subjects, up to 16 years of age, who had been investigated with a peanut or tree nut food challenge were eligible for the study. Subjects were referred from either a tertiary allergy clinic or a community birth cohort. All subjects with a history suggestive of food allergy were offered a challenge unless there were features of anaphylaxis. Details of challenges were prospectively recorded. Results were modeled by using logistic regression.
Results: There was a total of 161 peanut challenges. Recent skin prick (longest wheal diameter) and specific IgE data were available for 135 and 136 challenges, respectively. The results suggest that a skin prick result = 8 mm and a specific IgE = 15 kUA/L have predictive values of 95% (95% CI, 76.2% to 99.9%) and 92.0% (74.0% to 99.0%), respectively, for a positive challenge. Age, the type of nut, and referral pattern of the subject did not appear to alter this relationship.
Conclusion: These data suggest that a skin prick result = 8 mm or a specific IgE = 15 kUA/L have a high predictive value for clinical allergy to peanut and that these cutoff figures appear generalizable to different populations of children undergoing an assessment for peanut allergy.
5. Rancé, Fabienne, Michel Abbal, and Valérie Lauwers-Cancès. "Improved screening for peanut allergy by the combined use of skin prick tests and specific IgE assays." Journal of allergy and clinical immunology 109.6 (2002): 1027-1033.
Abstract
Background: The diagnosis of peanut allergy must be based on reliable, safe criteria. Double-blind, placebo-controlled food challenges (DBPCFCs) are the gold standard but are costly and dangerous because they can trigger severe reactions.
Objective: The aim of this study was to develop a new strategy for diagnosing peanut allergy while reducing the need for DBPCFCs.
Methods: We studied 363 children referred for an evaluation of suspected food hypersensitivity. They all benefited from the same diagnostic strategy, which included, in order, clinical history, a skin prick test (SPT), and a specific IgE assay. DBPCFCs were performed on all the children by personnel who were unaware of the results of the other tests. To assess the performance characteristics of the SPT (comparing commercial and raw peanut extracts) and the specific IgE assay, we compared the results with those provided by the DBPCFCs. For SPTs and specific IgE assays, we sought to determine the cutoff values required to exclude false-positive and false-negative results.
Results: According to DBPCFC results, 177 children were allergic to peanut, and 186 were not. The performance characteristics of the SPTs were superior with the raw extract because the negative predictive value was 100% (95% confidence interval [CI], 97.5-100). If the skin reaction with the raw extract was less than 3 mm, we could be quite certain that the child was not allergic. On the other hand, if the SPT resulted in a wheal diameter of larger than 3 mm, we could only be 74% certain that the children were allergic. Furthermore, if the SPT resulted in a wheal diameter of 16 mm or larger, we could be quite certain that the child was allergic because the positive predictive value was 100% (95% CI, 86.8-100). Specific IgE concentrations of 57 kUA/L or greater were associated with a positive predictive value of 100% (95% CI, 87.2-100). The combined use of the tests resulting in a positive diagnosis if the SPT result was 16 mm or larger or specific IgE concentration was 57 kUA/L or greater and in a negative diagnosis if the SPT result was less than 3 mm and the specific IgE concentration was less than 57 kUA/L allowed us to classify subjects with almost complete certainty as being allergic or not because the predictive values were 100%.
Conclusion: Commercial extracts could not be used to reliably predict tolerance of peanut. Peanut DBPCFCs can be avoided when SPTs with raw extracts resulted in wheals with a largest diameter of less than 3 mm and a specific IgE concentration of less than 57 kUA/L and also when wheal diameters were 16 mm or larger or specific IgE values were 57 kUA/L or greater. Otherwise, DBPCFCs were indispensable for the unequivocal diagnosis of peanut allergy. (J Allergy Clin Immunol 2002;109:1027-33.)
I heard from Dr. Burks:
I think your answer is all good; the likelihood of this child reacting to peanut is really very low. With a negative serum IgE and components and on 4 mm SPT, most all of those patients will be negative challenges. For the SPT guidelines, in general most of the literature is more toward the 8 mm and above for predicting a positive challenge. I agree on the pea also to challenge at some point and there is not a need to avoid the other legumes.
I hope this information is of use to you and your patient.
All my best.
Dennis K. Ledford, M.D., FAAAAI