背景:万古霉素输注反应(VIR),据报道,通过Mas相关G蛋白偶联受体X2(MRGPRX2)介导,是主要的万古霉素诱导的即时药物反应(IDR)。临床上,区分潜在的药物诱导的IDR机制对于未来的治疗策略至关重要,包括药物限制,重新管理,和预处理注意事项。然而,缺乏经过验证的诊断测试使得这具有挑战性,经常导致不必要的药物限制。
目的:为了确定皮内试验(IDTs)和,分开,嗜碱性粒细胞激活试验(BAT)将VIR与万古霉素耐受受试者区分开。
方法:对有和没有VIR病史的暴露于万古霉素的成年人进行横断面研究。人口统计,过敏相关的合并症,万古霉素暴露史,并收集了VIR特征。用万古霉素进行IDT。IDT剂量反应EC50,IDT相关局部症状,组间比较BAT和BAT。
结果:纳入11例VIR和10例万古霉素耐受受试者。报告最多的VIR症状是瘙痒(82%),冲洗(82%),蜂箱(46%),蜂箱(46%),血管性水肿(27%),和呼吸困难(19%)。在VIR中,IDT剂量反应平均EC50为328μg/mL(95%CI296,367)。耐受组1,166μg/mL(95%CI1029,1379)(p<0.0001)。所有VIR受试者报告IDT相关的局部瘙痒,而耐受性受试者为60%(p=0.0185)。CD63+嗜碱性粒细胞百分比始终<2%,组间无显著差异(p<0.54)。
结论:皮肤测试方法的变化可能有助于确定IgE以外的其他IDR机制。这种皮肤测试方案具有识别VIR的潜力,特别是在患者接受多种药物而BAT不足的情况下。未来的研究将验证和描绘其预测价值,评估VIR的风险。
BACKGROUND: Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2), is the primary vancomycin-induced immediate drug reaction (IDR). Clinically, distinguishing the underlying drug-induced IDR 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 if intradermal tests (IDTs) and, separately, the basophil activation test (BAT) differentiate VIR from vancomycin-tolerant subjects.
METHODS: Cross-sectional study of vancomycin-exposed adults with and without a history of VIR. Demographics, allergy-related comorbidities, history of vancomycin exposures, and VIR characteristics were collected. IDT with vancomycin was performed. IDT dose responses EC50, IDT-related local symptoms, and BAT were compared between groups.
RESULTS: 11 VIR and 10 vancomycin-tolerant subjects were enrolled. The most reported VIR symptoms were pruritus (82%), flushing (82%), hives (46%), hives (46%), angioedema (27%), and dyspnea (19%). The IDT dose response mean EC50 was 328 μg/mL (95% CI 296, 367) in the VIR vs. 1,166 μg/mL (95% CI 1029, 1379) in the tolerant group (p<0.0001). All VIR subjects reported IDT-related local pruritus compared to 60% of tolerant subjects (p=0.0185). The %CD63+ basophils were consistently <2%, without significant differences between groups (p < 0.54).
CONCLUSIONS: Variations in skin test methodologies could help identify other IDR 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.