Two-step algorithm improves cashew allergy testing
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A two-step algorithm improved the accuracy and reduced the need for oral food challenges in diagnosing cashew allergy in children, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
OFCs provide definitive diagnoses for food allergies, but their availability is limited, and they are expensive and labor-intensive, according to the researchers.
“We previously published a systematic review on the accuracy of diagnostic tests in food allergy and found that the cashew nut component Ana o3 performed more accurately than cashew skin prick or cashew-specific IgE alone,” Tim Brettig, MBBS, a pediatric allergist and immunologist at The Royal Children’s Hospital in Parkville, Australia, told Healio.
“This study arose from this observation, and I wanted to see whether different populations would display a similar outcome, where the populations and prevalence of cashew nut allergy are different,” said Brettig, who also is a research study doctor currently undertaking a PhD focused on the diagnosis and management of childhood tree nut allergy at Murdoch Children’s Research Institute in Parkville.
The researchers pooled individual-level data from six studies on the sensitivity, specificity and positive and negative predictive values for diagnostic tests for cashew allergy diagnosis including skin prick testing, cashew-specific IgE (sIgE) and Ana o3 sIgE.
A total of 567 participants from the studies underwent SPT, with 34.9% found allergic and 65.1% tolerant. According to the data, 58.4% required an OFC to determine their allergy status, and 97.2% were correctly identified as allergic or tolerant. False-negative results occurred in 2.3% of participants, while false-positive results occurred in 0.5%.
For the two-step algorithm — which used cashew sIgE and Ana o3 sIgE — the researchers used an upper-limit cutoff of at least 8.5 kUA/L for cashew sIgE, indicating cashew should be avoided. A lower-limit cutoff of 0.1 kUA/L or lower for cashew sIgE prompted home introduction, whereas participants with a result between the two cutoffs proceeded to Ana o3 IgE testing. A lower-limit cutoff of 0.1 kUA/L or lower for Ana o3 IgE also prompted home introduction and an upper-limit cutoff of at least 0.35 kUA/L lead to avoidance, whereas results between the two led to OFC testing.
A total of 271 participants underwent the two-step testing method, with 57.6% found allergic and 42.4% tolerant. In this cohort, 11.4% required an OFC to determine allergy status, which represented an 80.4% reduction compared with the SPT pathway.
Also, 74.5% of the participants who underwent the two-step algorithm required Ana o3 testing, and 91.1% were correctly identified as allergic or tolerant. Additionally, 1.1% had false-negative results, and 8.1% had false-positives.
The same 271 participants underwent cashew sIgE and Ana o3 sIgE testing individually. Ana o3 sIgE testing required OFC in 12.2% of participants and yielded 91.9% correct diagnoses. Cashew sIgE testing alone required OFC in 74.5% of participants with 98.2% correct diagnoses.
“Our initial hypothesis was that a two-step algorithm (cashew sIgE followed by Ana o3 sIgE) would provide greater diagnostic accuracy compared with cashew SPT alone. We did not expect Ana o3 sIgE alone to perform so well, in particular having the same proportion of false-negative results to the two-step algorithm,” Brettig said.
The greater diagnostic accuracy and reduced need to proceed to an OFC for a definitive diagnosis that results from Ana o3 and/or a two-step algorithm would be especially beneficial in settings with limited access to OFCs, Brettig continued. However, he added, the cutoffs used in these algorithms might not be optimal and they would need to be defined in future larger-scale prospective cohort studies.
Further, Brettig said, this protocol may be applicable to other food allergies.
“A two-step algorithm has been shown to reduce the number of oral food challenges required for diagnosis of peanut allergy or walnut allergy,” he said. “Given the limitations in diagnostic accuracy for other foods, especially tree nuts, it would be very reasonable to expect that similar approaches could be used.”
Future research will continue to explore the accuracy of diagnostic tools in the assessment of childhood food allergy, Brettig said.
For more information:
Tim Brettig, MBBS, can be reached at tim.brettig@mcri.edu.au.
References:
Dang, TD, et al. J Allergy Clin Immunol. 2012;doi:10.1016/j.jaci.2012.01.56.
Dunne J, et al. BJOG. 2021;doi:10.1111/1471-0528.17007.
Goldberg MR, et al. J Allergy Clin Immunol Pract. 2021;doi:10.1016/j.jaip.2020.09.041.
Perspective
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These results are not too surprising. We know that Ana o3 is probably a more specific test to diagnose peanut allergy than SPT and serum IgE to cashew. So, if you set up an algorithm that runs the test with the better specificity after a test with good sensitivity, you will probably increase diagnostic accuracy.
But the study did not show the cost of this method. Or why not do an SPT first and then Ana o3? It would probably be just as good as this study’s proposed method of serum and then Ana o3. Or for that matter, why not just do Ana o3? It seemed to perform just as well as the proposed two-step algorithm.
Although these results do line up with my experience, I don’t use the tests sequentially like that. But the reasoning does line up with how I practice. Allergists should be willing to challenge a patient if the diagnosis is ever in question and the family has a desire to pursue challenge, and it appears that Ana o3 is perhaps the most accurate test overall.
Based on this one report, though, I don’t think I will be checking sIgE to cashew and Ana o3 on all patients. I think you could convince me that based upon available data, Ana o3 is the best overall test, and perhaps it should be the test used if you are only going to order one.
However, in the end, we need cost-effective analysis to tell us how to best minimize testing and get to the correct diagnosis.
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