D1.82 - Diagnostic challenges in amoxicillin-clavulanate anaphylaxis: an inconclusive in vitro study – Case Report

Background: Severe immediate hypersensitivity reactions approach includes skin prick (SPT) and intradermal (IDT) tests, which is not risk-free. In vitro tests offer a safer initial approach. Specific immunoglobulins E (sIgE) are available for β-Lactams antibiotics. Basophil activation test (BAT) could be a complementary tool when sIgE are inconclusive, or skin testing is not the safest. We present an anaphylaxis diagnostic approach following amoxicillin-clavulanate (AX-CLV) intake case, with undetectable sIgE levels and an indeterminate BAT.

Case Report: A 40-year-old healthy man presented to the emergency department with generalized pruritic maculopapular erythematous lesions 20 minutes after AX-CLV 875/125 mg for a dental abscess. He also exhibited lip edema without respiratory or hemodynamic compromise. Symptoms solved after intravenous antihistamines and corticosteroids. He was referred to an allergology appointment. Acute tryptase level was 24.2 µg/L (baseline: 4.85 µg/L). An anaphylaxis was assumed, in vitro testing was scheduled, and β-lactam avoidance was recommended. Penicillin G, penicillin V, ampicillin, amoxicillin, and cefaclor sIgE levels (singleplex immunoassay), collected post-recovery, were 0.02, 0.03, 0.03, 0.03, and 0.16 kUA/L, respectively. A BAT with AX-CLV extract (flow cytometry-based assay) was requested, within an optimal time window and resulting in a stimulation index (SI) ≥ 5, but only 1% activated basophils (CD63+), which suggest no significant activation. In vitro testing was not very enlightening, but it allowed SPT and IDT with cefoxitin and ceftriaxone that were negative, such as a cefuroxime oral provocation challenge, also negative.

Conclusion: Results did not exclude amoxicillin or clavulanate as culprit. AX-CLV, and structurally related β-lactams, strict avoidance remains necessary. We emphasize Cefaclor sIgE expressed a subthreshold sensitization, while BAT met one (SI ≥ 2) of the two EAACI criteria recommendations to a positive result. The lack of CD63 expression (> 5%) could be attributed to basophil response heterogeneity and marker sensitivity limitations. These findings posed diagnostic challenges and further testing is needed. Combining CD203c appears to improve BAT sensitivity for AX-CLV. A definitive diagnosis was not established, but assuming a false negative case, in vivo alternative testing tolerance is in line with literature, and most second- and third-generation cephalosporins are considered safe.