A Skin Testing Strategy for Non-IgE-Mediated Reactions Associated With Vancomycin

Abstract

Background: Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2, is the primary vancomycin-induced immediate drug reaction. Clinically, distinguishing the underlying drug-induced immediate drug reaction mechanisms is crucial for future treatment strategies, including drug restriction, re-administration, and pretreatment considerations. However, the lack of validated diagnostic tests makes this challenging, often leading to unnecessary drug restriction.

Objective: To determine whether intradermal tests (IDTs) and, separately, the basophil activation test (BAT) differentiate VIR from vancomycin-tolerant subjects.

Methods: This was a cross-sectional study of vancomycin-exposed adults with and without a history of VIR. Data on demographics, allergy-related comorbidities, history of vancomycin exposures, and VIR characteristics were collected. IDT with vancomycin was performed. IDT dose-response EC₅₀, IDT-related local symptoms, and BAT results were compared between groups.

Results: A total of 11 VIR and 10 vancomycin-tolerant subjects were enrolled. The most reported VIR symptoms were pruritus (82%), flushing (82%), hives (46%), angioedema (27%), and dyspnea (19%). The IDT dose-response mean EC₅₀ was 328 μg/mL (95% CI, 296-367) in the VIR versus 1166 μg/mL (95% CI, 1029-1379) in the tolerant group (P < .0001). All VIR subjects reported IDT-related local pruritus compared with 60% of tolerant subjects (P = .0185). The %CD63⁺ basophils were consistently less than 2%, without significant differences between groups (P < .54).

Conclusions: Variations in skin test methodologies could help identify other immediate drug reaction mechanisms beyond IgE. This skin test protocol holds the potential for identifying VIR, particularly in cases where patients have received multiple drugs while BAT is insufficient. Future studies will validate and delineate its predictive value, assessing the risk of VIR.

Keywords: Basophil activation test; Dose-response curve; Drug allergy; Immediate drug reaction; MRGPRX2; MRGPRX2 ligands; Non-IgE-mediated immediate drug reaction; Skin test; Vancomycin infusion reaction.