Basophil CD63 assay to peanut allergens accurately diagnoses peanut allergy in patient with negative skin prick test and very low specific IgE.

To the Editor, Fatal food anaphylaxis commonly occurs amongst patients who had previously only reported mild symptoms.1 An accurate diagnosis of food allergy is crucial. Current diagnostic practice relies on evaluating the strength of clinical history and seeking objective validation from the level of IgE sensitisation, investigated by skin prick test (SPT) or serumspecific IgE (sIgE). However, single timepoint sensitisation assays are usually sensitive but not specific— in particular, black ethnicity has been associated with raised levels of sIgE to peanut that are often clinically irrelevant.2 Oral food challenges (OFCs) are routine in clinical practice, exposing large numbers of patients to further food allergic reactions.3 Functional assays such as the basophil activation test (BAT) can discriminate between sensitisedtolerant and sensitisedallergic patients because it more closely resembles the pathological reaction of effector cells towards the culprit allergen.4,5 We have shown that the BAT is the single most accurate test to diagnose peanut allergy (PA) with enhanced specificity and retained sensitivity when compared to sensitisation tests.6 BAT investigation alongside serum and skin sensitisation testing can reduce the number of children who would be required to undergo OFC testing by two thirds.6 Other clinical presentations may prove of particular relevance. Herein, we report a case with negative SPT and very low allergen sIgE who nevertheless reacted on OFC to roasted peanuts and demonstrated activation of basophils on stimulation with peanut extract, Ara h 1, Ara h 2 and Ara h 6. A 12yearold girl of AfroCaribbean descent presented to our clinic to ascertain whether she needed to avoid nuts. At 4 years of age, she had drunk a freshly made fruit drink containing peanut and developed facial angioedema afterwards, although the exact time course was not remembered. On a second occasion, she developed conjunctivitis when a friend ate peanuts whilst being sat next to her. She had no history of allergic rhinitis. Investigations revealed a negative SPT to peanut (0 mm) and very low sIgE to peanut (0.15 kUA/L) and to Ara h 2 (0.11 kUA/L). SIgE to Ara h 1, Ara h 3, Ara h 8 and Ara h 9 was undetectable. Her baseline tryptase was 3.0 μg/L, and there was no wheal to any of the other eight tree nuts skin tested in clinic. An open incremental OFC was scheduled with the aim to rule out PA. The patient tolerated the first four doses. However, after eating the last open dose totalling a cumulative portion of 32 grams of dry roasted peanuts (8 g of peanut protein), she developed nasal congestion and prominent swelling of her eyelids, brow and lips. She reported subjective difficulty in breathing; however, her voice was clear, her oxygen saturations remained over 98% and there was no increase in her respiratory rate or blood pressure. She was treated with 10 mg of cetirizine followed by 120 mg of fexofenadine and her reaction subsided. She was advised to avoid peanut. Basophil activation test performed after the OFC demonstrated a significant response to peanut extract, Ara h 1, Ara h 2 and Ara h 6 but no response to Ara h 3 or Ara h 8 (Figure 1). The result of BAT to peanut was above the diagnostic cutoff previously defined in our patient population.6 A dosedependent increase in CD63 and CD203c expression with increasing concentrations of peanut extract, Ara h 2 and Ara h 6, was observed (Figure 2). On the same day as the BAT, she did not show sIgE to any of the 112 allergens tested on ImmunoCAP ISAC other than Ara h 2 and Ara h 6 (rAra h 2=0.3 ISU; rAra h 6=0.6 ISU). The results of Ara h 2specific IgE were low before and after the OFC. This clinical case shows that BAT was more sensitive than SPT (which showed no wheal for this patient), sIgE and even component testing and can be useful when there is discrepancy between the clinical history and IgE sensitisation tests. Although the patients' ethnicity could have suggested that the sIgE results were not clinically relevant, the history of possible peanut reactions led us to decide for an OFC, which should be considered gold standard care for patients with discrepant history and sensitisation results. This case also highlights the need for further investigation amongst patients who report reactions to the allergen with negligible sensitisation. Before BAT can replace OFC in this setting, a larger case series with sufficient power to confirm this would be valuable. However, in previous studies, we have already observed that although peanut allergic with low level of sensitisation is a minority (e.g. 9% in the overall population studied by Santos et al6), BAT is positive in a significant proportion of these cases (e.g. 73%), allowing to confirm the diagnosis of peanut allergy and deferring an OFC that would otherwise have been positive. Without using BAT or OFC, this patient would have had no confirmation of PA and be at risk of further allergic reactions in the community.