Demir Semra, Erdenen Fusun, Gelincik Asli, Unal Derya, Olgac Muge, Coskun Raif, Colakoglu Bahauddin, Buyukozturk Suna
Adult Allergy and Immunology Clinic, Istanbul Research and Training Hospital, Health Science University, Istanbul, Turkey,
Adult Allergy and Immunology Clinic, Istanbul Research and Training Hospital, Health Science University, Istanbul, Turkey.
Int Arch Allergy Immunol. 2019;178(2):167-176. doi: 10.1159/000494130. Epub 2018 Nov 16.
To investigate the potential risk factors in patients who have experienced anaphylaxis from drugs.
The study included 281 adult patients (median age 40 years; 76.5% female) who experienced immediate types of hypersensitivity reaction to a drug. The patients were divided into an anaphylaxis group and a nonanaphylaxis group. The anaphylaxis group was diagnosed according to the criteria of the World Allergy Organization. Skin testing with culprit drugs was performed. In the nonanaphylaxis group, drug provocation tests were performed with culprit drugs, including aspirin or diclofenac, to determine nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Atopy was determined by skin prick tests with the common inhalant allergens. Patients' demographics, clinical features, and baseline tryptase and total IgE levels were compared between the 2 groups.
The median interval between the last reaction in the patient's history and the study evaluation was 7 months (range 1-120 months). In 52.3% of the patients, reactions were defined as anaphylaxis. The most common culprit drugs were NSAIDs (56.9%) and β-lactams (34.7%). The culprit drugs were used parenterally in 13.2% of the patients. 34.9% of the patients had comorbid diseases and 24.6% used additional drugs, the most common being antihypertensives (10%). Atopy was determined in 28.8% and 28.1% of the patients were smokers. The median serum level of baseline tryptase and total IgE was 3.5 µg/L and 77 kU/L, respectively. In 46.3% of the patients, skin tests with culprit drugs were positive and the positivity ratio was higher in the anaphylaxis group (p = 0.002). Anapyhlaxis was more common in patients who were: hypertensive, atopic, using angio-tensin-converting enzyme inhibitors/angiotensin receptor blockers, and received the culprit drug parenterally (p = 0.034, p = 0.04, p = 0.03, p = 0.035, p = 0.013, and p < 0.001). In the multivariate analysis, it was observed that the parenteral usage of the drug and the presence of atopy were significantly higher in the anaphylaxis group (p < 0.001, odds ratio [OR] = 20.05, confidence interval [CI] 4.75-88.64; p = 0.012, OR = 2.1, CI 1.17-3.74). Age, smoking, family history, and serum levels of baseline tryptase and total IgE did not differ between groups.
The parenteral route and atopy increase the risk of drug-induced anaphylaxis. IgE-mediated sensitivity to the culprit drug seems to facilitate anaphylaxis.
调查发生药物过敏反应患者的潜在风险因素。
本研究纳入了281例成年患者(中位年龄40岁;76.5%为女性),这些患者对药物发生速发型超敏反应。将患者分为过敏反应组和非过敏反应组。过敏反应组根据世界过敏组织的标准进行诊断。对可疑药物进行皮肤试验。在非过敏反应组,对包括阿司匹林或双氯芬酸在内的可疑药物进行药物激发试验,以确定非甾体抗炎药(NSAID)超敏反应。通过对常见吸入性变应原进行皮肤点刺试验来确定特应性。比较两组患者的人口统计学特征、临床特征以及基线类胰蛋白酶和总IgE水平。
患者病史中最后一次反应与研究评估之间的中位间隔时间为7个月(范围1 - 120个月)。52.3%的患者反应被定义为过敏反应。最常见的可疑药物是NSAIDs(56.9%)和β-内酰胺类(34.7%)。13.2%的患者经胃肠外途径使用可疑药物。34.9%的患者患有合并症,24.6%的患者使用其他药物,最常见的是抗高血压药(10%)。28.8%的患者被确定为特应性,28.1%的患者为吸烟者。基线类胰蛋白酶和总IgE的中位血清水平分别为3.5 μg/L和77 kU/L。46.3%的患者对可疑药物的皮肤试验呈阳性,且过敏反应组的阳性率更高(p = 0.002)。过敏反应在以下患者中更常见:高血压患者、特应性患者、使用血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂的患者以及经胃肠外途径使用可疑药物的患者(p = 0.034、p = 0.04、p = 0.03、p = 0.035、p = 0.013和p < 0.001)。在多变量分析中,观察到过敏反应组中药物的胃肠外使用和特应性的存在显著更高(p < 0.001,比值比[OR] = 20.05,置信区间[CI] 4.75 - 88.64;p = 0.012,OR = 2.1,CI 1.17 - 3.74)。两组之间的年龄、吸烟、家族史以及基线类胰蛋白酶和总IgE水平无差异。
胃肠外途径和特应性增加了药物诱导的过敏反应风险。对可疑药物的IgE介导的敏感性似乎促进了过敏反应。