二巯丙磺钠注射液致肝豆状核变性患者过敏反应危险因素及其预测价值分析

Risk factors of anaphylaxis caused by sodium dimercaptopropane injection in patients with hepato⁃lenticular degeneration and an analysis of its predictive value

目的分析二巯丙磺钠(DMPS)注射液致肝豆状核变性(HLD)患者过敏反应的危险因素及其对过敏反应风险的预测价值。方法收集2019年1月至2021年12月因HLD首次在安徽中医药大学第一附属医院住院且接受DMPS治疗患者的电子病历,记录患者基本信息、应用DMPS前有关实验室指标检查结果、DMPS日剂量及过敏反应发生情况、治疗和转归。根据是否发生DMPS相关过敏反应将患者分为过敏组和对照组,比较2组患者临床特征,采用二元logistic回归法分析DMPS致过敏反应的危险因素,计算比值比(OR)及其95%置信区间(CI);将所有独立危险因素合并为联合预测因子,应用受试者工作特征(ROC)曲线分析单个危险因素和联合预测因子对过敏反应发生风险的预测价值。结果纳入分析的患者共477例。过敏组124例,男性80例,女性44例,年龄1~51岁,<18岁者55例;对照组353例,男性237例,女性116例,年龄2~66岁,<18岁者106例。过敏组124例患者共发生过敏反应191例次,主要表现为皮肤瘙痒(67例次、35.1%)和药物性皮炎(58例次、30.4%);发生过敏反应的时间为用药第1~5个疗程,发生在第1、2个疗程者分别为74例(59.7%)和31例(25.0%)。发生过敏反应后所有患者均停用DMPS,5例因症状轻微未予其他干预,其余患者予抗过敏治疗后症状均消退。2组患者比较,年龄、入院前DMPS用药史、药物过敏史,以及应用DMPS前外周血淋巴细胞计数、铜蓝蛋白、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶、碱性磷酸酶(ALP)、γ-谷氨酰转移酶、乳酸脱氢酶和血尿素氮水平差异有统计学意义(均P<0.05)。二元logistic回归分析显示,药物过敏史(OR=3.698,95%CI:2.233~6.124,P<0.001)、用药前ALT水平(OR=1.004,95%CI:1.000~1.007,P=0.044)和ALP水平(OR=1.003,95%CI:1.002~1.005,P<0.001)是DMPS致HLD患者过敏反应的独立危险因素。ROC曲线分析显示,用药前ALT水平曲线下面积(AUC)为0.613(95%CI:0.553~0.673),截断值50 U/L,敏感度0.419,特异度0.788;用药前ALP水平AUC为0.600(95%CI:0.537~0.663),截断值202 U/L,敏感度0.411,特异度0.816。将过敏史与用药前ALT、ALP水平经logistic回归模型转换生成联合预测因子,ROC曲线分析结果显示,联合预测因子AUC为0.703(95%CI:0.648~0.757),截断值0.465,敏感度0.685,特异度0.657。结论药物过敏史、用药前ALP和ALT水平是DMPS致HLD患者过敏反应的独立危险因素,联合预测因子对DMPS致HLD患者过敏反应的发生有预测价值。

Objective To analyze the risk factors of anaphylaxis caused by sodium dimercapto-propane sulfonate(DMPS)in patients with hepatolenticular degeneration(HLD)and its predictive value.Methods The electronic medical records of patients who were hospitalized for the first time in the First Affiliated Hospital of Anhui University of Chinese Medicine due to HLD from January 2019 to December 2021 and received DMPS treatment were collected.The basic information,relevant laboratory test results before the application of DMPS,daily dose of DMPS,and occurrence,treatment and outcome of allergic reac⁃tions in patients were recorded.The patients were divided into allergy group and control group based on whether DMPS⁃related anaphylaxis occurred.The clinical characteristics in patients in the 2 groups were compared.The risk factors of DMPS⁃induced anaphylaxis were analyzed using binary logistic regression,and the odds ratio(OR)and its 95%confidence interval(CI)were calculated.All independent risk factors were merged into joint predictor and the predictive value of individual risk factors and joint predictor for risk of anaphylaxis were analyzed using receiver operating characteristic(ROC)curve.Results A total of 477 patients were enrolled in the study,including 124 patients in the allergy group and 353 patients in the control group.Among the 124 patients in the allergy group,80 were male and 44 were female,aged 1⁃51 years,with 55 patients<18 years of age.Among the 353 patients in the control group,237 were male and 116 were female,aged 2⁃66 years,with 106 patients<18 years of age.A total of 191 times of allergic reactions occurred in patients in the allergy group,the main manifestations were pruritus(67 times,35.1%)and drug⁃induced dermatitis(58 times,30.4%).The allergic reactions occurred during the 1st to the 5th course of treatment,with 74(59.7%)and 31 cases(25.0%)occurring in the 1st and 2nd course of treatment,respectively.DMPS was discontinued in all patients.Of them,5 patients did not receive any intervention because of mild symp⁃toms and the rest were treated with glucocorticoids and/or antihistamines,and the symptoms of anaphylaxis subsided.The differences in age,DMPS medication history before admission,drug allergy history,and peripheral blood lymphocyte count,ceruloplasmin,alanine aminotransferase(ALT),aspartate aminotransferase,alkaline phosphatase(ALP),γ⁃glutamyltransferase,lactate dehydrogenase,and blood urea nitrogen levels before DMPS application between the 2 groups were statistically significant(all P<0.05).Binary logistic regression analysis showed that the history of drug allergy(OR=3.698,95%CI:2.233-6.124,P<0.001),the level of ALT before medication(OR=1.004,95%CI:1.000-1.007,P=0.044)and the level of ALP before medication(OR=1.003,95%CI:1.002-1.005,P<0.001)were independent risk factors for allergic reactions caused by DMPS in HLD patients.ROC curve analysis showed that the area under the curve(AUC)of ALT level before medication was 0.613(95%CI:0.553-0.673),the cutoff value was 50 U/L,the sensitivity was 0.419,and the specificity was 0.788;the AUC of ALP level before medication was 0.600(95%CI:0.537-0.663),the cutoff value was 202 U/L,the sensitivity was 0.411,and the specificity was 0.816.Allergy history,ALP and ALT levels before medication were converted into joint predictor by logistic regression model.ROC curve analysis showed that the AUC of joint predictor was 0.703(95%CI:0.648-0.757),the cutoff value was 0.465,the sensitivity was 0.685,and the specificity was 0.657.Conclusions The history of drug allergy,the level of ALT and ALP before medication are independent risk factors of anaphylaxis induced by DMPS in HLD patients.The joint predictor has good predictive value for anaphylaxis induced by DMPS in HLD patients.