Diagnosis of immediate reactions to amoxicillin: Comparison of basophil activation markers CD63 and CD203c in a prospective study

Abstract

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.

Biomarkers of immediate drug hypersensitivity

“…and CD203c, in a prospective evaluation of amoxicillin (AX) and CLV allergic patients showed that the best sensitivity and specificity was obtained for CD203c (46.6% and 94.6%), with good positive predictive value and like-hood ratio. 43 These results are in line with those obtained by Abuaf et al 44 However, another recent study in IDHRs to AX obtained lower sensitivity (23%) when selecting a high specificity (95%). 45 All this suggests that methodological or analytical variations in the classical procedure could be useful to improve the diagnostic value of BAT.…”

Reply to correspondence to ‘Diagnosis of immediate reactions to amoxicillin: Comparison of basophil activation markers CD63 and CD203c in a prospective study’

“…Finally, we thank the authors for the figure S2 observation. 2 Certainly, part A does not correspond to individual results, it has beenamistakeandtherepresentationcorrespondstoSIresultsin-stead%results.ThecorrectgraphisshowninFigure 1B.…”

Correspondence to “Diagnosis of immediate reactions to amoxicillin: Comparison of basophil activation markers CD63 and CD203c in a prospective study”

“…We read the paper by Céspedes et al 1 with interest. However, we respectfully disagree with their generalizing proposal placing the basophil activation test (BAT) as a primary diagnostic in the diagnostic algorithm to document immediate hypersensitivity to amoxicillin.…”

“…From the literature, it has emerged that 90% of “penicillin‐allergic” patients tolerate the alleged culprit(s) 6–9 . However, the authors 1 document an immediate allergy to amoxicillin (AX) or clavulanic acid in 66% of their patients. This likely relates to their study population.…”

“…Moreover, calculating positive and negative predictive values taking into account the prevalence of β‐lactam allergy in the general population would be more informative. Therefore, the evidence provided by Céspedes et al 1 for placing the BAT as a primary test in the diagnosis of immediate amoxicillin hypersensitivity needs critical interpretation and verification.…”