Direct Single-Dose Drug-Provocation Test Is Safe for Delabelling Penicillin Low-Risk Reactions in Adults

Abstract

Background: Penicillins (PENs) are the most frequent drug-allergic reactions trigger. However, diagnostic work-up is complex and time-consuming: it requires skin testing (ST) and drug-provocation test (DPT), needing faster delabelling strategies. Although direct DPT without previous STs has shown to be safe, most of the studies are performed in children or in North American, Asian, or Oceanian adults, with few studies in the European adult population. We explored its safety in European adult patients with low-risk PEN allergy history and, additionally, analysed ST role and T-cell involvement by lymphocyte trans- formation test (LTT). Methods: We prospectively evaluated > 16 years of PEN-allergic labelled patients referred to Málaga Regional University Hospital during 2023. They reported non-immediate reactions without alarm signs and unknown reactions. Direct-single-dose DPT was performed in all patients. If positive, ST and LTT were carried out after reaction resolution. Results: We included 269 patients with the culprits being an unidentified PEN (36%), amoxicillin (AX) (32%), and AX-clavulanic acid (AX- CLV) (31%); and the symptoms maculopapular exanthema (MPE) (34%) and unknown reaction during childhood (23%). Only 16 (5.9%) had positive DPT, being 56% for AX and 44% for AX- CLV, 81% developing MPE, none severe. Most DPT-reacting patients reported cutaneous non-immediate reactions in the index reaction, and only one had an unknown childhood reaction. The mean day interval between drug administration and symptom development was lower (p = 0.002) in positive DPT than in the index reaction (2 vs 5 days). Moreover, ST was positive in only 19% and LTTs in 86.7% of positive DPT patients. Conclusions: Direct-single-dose DPT is safe for delabelling PEN allergy in non-immediate reactions without alarm signs and unknown reactions. ST had a poor diagnostic value and LTT had a high one, confirming a T-cell involvement.