BackgroundAmoxicillin (AX) combined or not with clavulanic acid (CLV) is frequently involved in IgE‐mediated reactions. Drug provocation test (DPT) is considered as the gold standard for diagnosis, although contraindicated in high‐risk patients. Basophil activation test (BAT) can help diagnose immediate reactions to beta‐lactams, although controversy exists regarding the best activation marker. We have performed a real‐life study in a prospective cohort to analyze the real value of BAT as diagnostic tool and the best activation marker, CD63 and CD203c, for the evaluation of immediate reactions to these drugs.MethodsWe prospectively evaluated patients with a clinical suspicion of immediate reactions after AX or AX‐CLV administration during a 6‐year period. The allergological work‐up was done following the EAACI recommendations. BAT was performed in all patients using CD63 and CD203c as activation markers.ResultsIn AX‐allergic patients, both activation markers, CD63 and CD203c, showed similar SE values (48.6% and 46.7%, respectively); however, specificity was of 81.1% and 94.6%, respectively, with CD203c showing good positive predictive value and like‐hood ratio. In CLV‐allergic patients, CD203c showed higher SE (50%) than CD63 (42.9%), maintaining the same value of SP (80%). Combining the results of both markers can slightly increase the sensitivity (51.4% for AX and 54.8% for CLV), although decreasing the specificity (79.7% and 73%, respectively). Interestingly, all patients with an anaphylactic shock showed a positive BAT to CLV using CD203c.ConclusionsBAT using CD203c showed a good confirmatory power, especially for AX allergy. Placing BAT as a first step in the diagnostic procedure can help reduce the need of performing a complete allergological work‐up in 46.6% of patients, diminishing the risk of reinducing allergic reactions.

Background Immediate drug hypersensitivity reactions (IDHRs) to clavulanic acid (CLV) have increased in the last decades due to a higher consumption alongside amoxicillin (AX). Due to its chemical instability, diagnostic procedures to evaluate IDHRs to CLV are difficult, and current in vitro assays do not have an optimal sensitivity. The inclusion of the specific metabolites after CLV degradation, which are efficiently recognised by the immune system, could help to improve sensitivity of in vitro tests. Methods Recognition by dendritic cells (DCs) of CLV and the synthetic analogues of two of its hypothesised antigenic determinants (ADs) was evaluated by flow cytometry in 27 allergic patients (AP) and healthy controls (HC). Their ability to trigger the proliferation of T cells was also analysed by flow cytometry. Results The inclusion of synthetic analogues of CLV ADs, significantly increased the expression of maturation markers on DCs from AP compared to HC. A different recognition pattern could be observed with each AD, and, therefore, the inclusion of both ADs achieves an improved sensitivity. The addition of synthetic ADs analogues increased the proliferative response of CD4+Th2 compared to the addition of native CLV. The combination of results from both ADs increased the sensitivity of proliferative assays from 19% to 65% with a specificity higher than 90%. Conclusions Synthetic ADs from CLV are efficiently recognised by DCs with ability to activate CD4+Th2 cells from AP. The combination of analogues from both ADs, significantly increased the sensitivity of DC maturation and T‐cell proliferation compared to native CLV.

Background:The diagnosis of allergic reactions to penicillins (AR-PEN) is very complex as there is a loss of sensitization over time, which leads to negative skin tests (STs) and specific IgE in serum, and even to tolerance to the drug involved. However, STs may become positive after subsequent exposure to the culprit drug (resensitization), with the risk of inducing potentially severe reactions. The exact rate of resensitization to penicillins is unknown, ranging from 0% to 27.9% in published studies. Objectives:To analyze the rate of resensitization in patients with suggestive AR-PEN by repeating STs (retest) after an initial evaluation (IE). Material and Methods:Patients with suspected AR-PEN were prospectively evaluated between 2017 and 2020. They underwent STs, and a randomized group also underwent a drug provocation test (DPT) with the culprit. Only patients with negative STs and/or DPT were included. All included cases were retested by STs at 2-8 weeks.Results: A total of 545 patients were included: 296 reporting immediate reactions (IRs) and 249 non-immediate reactions (NIRs). Eighty (14.7%) cases had positive results in retest (RT+): 63 (21.3%) IRs and 17 (6.8%) NIRs (p < 0.0001). The rate of RT+ was higher in anaphylaxis compared with all other reactions (45.8% vs 9.1%, p < 0.0001). The risk of RT+ was higher from the fifth week after IE (OR: 4.64, CI: 2.1-11.6; p < 0.001) and increased with the patient's age (OR: 1.02; CI: 1.01-1.04; p = 0.009). Conclusions:Due to the high rate of resensitization, retest should be included in the diagnostic algorithm of IRs to penicillins after an initial negative study, especially in anaphylaxis, to avoid potentially severe reactions after subsequent prescriptions of these drugs.