Sensitivity and specificity of the lymphocyte transformation test in drug reaction with eosinophilia and systemic symptoms causality assessment
Sensitivity and specificity of the lymphocyte transformation test in drug reaction with eosinophilia and systemic symptoms causality assessment
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DOI：
10.1111/cea.13076
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发表时间：
2018-03-01
影响因子：
6.1
通讯作者：
Bellon, T.
中科院分区：
文献类型：
--
作者：
Cabanas, R.;Calderon, O.;Bellon, T.
背景药物反应伴嗜酸性粒细胞增多和全身症状（DRESS）是一种严重的迟发性超敏反应。药物因果关系的确定是复杂的。据报道，淋巴细胞转化试验（LTT）在超过50%的DRESS病例中呈阳性。然而，LTT在DRESS中特异性的敏感性和特异性尚未确定。与罪犯药物的再激发是禁忌的，不能被用作金标准的灵敏度和特异性determination. Objectives估计的灵敏度和特异性LTT在一个临床定义的系列患者DRESS.MethodsSome 41例确诊为DRESS被列入研究。西班牙药物警戒系统的算法结果被用作正确诊断药物因果关系的标准。对急性或恢复期样本中的相关药物进行标准LTT。除β-内酰胺类（SI 3）和造影剂（SI 4）外，至少一种浓度的刺激指数（SI）2被视为阳性。结果DRESS恢复期LTT的敏感性和特异性分别为73%和82%，而急性期LTT的敏感性和特异性分别为40%和30%。皮肤试验和LTT的比较证实，LTT在DRESS中具有更高的敏感性和特异性。LTT显示抗惊厥药（S 100%，Sp 100%; P= 0.008）、抗结核药（S 87.5%，Sp 100%; P= 0.004）和β-内酰胺类药物（S 73%，Sp 100%; P= 0.001）的敏感性（S）和特异性（Sp）较高。ROC曲线显示，所有药物的最佳LTT阳性标准为至少一种浓度的SI 2，使总体敏感性提高到80%，β-内酰胺类药物的敏感性从73%提高到92%。结论和临床意义LTT是DRESS中药物因果关系的良好诊断工具，主要在恢复期进行。
BackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) is a severe delayed hypersensitivity reaction. The determination of drug causality is complex. The lymphocyte transformation test (LTT) has been reported positive in more than 50% of DRESS cases. Nevertheless, the sensitivity and specificity of LTT specifically in DRESS have not yet been established. Rechallenge with the culprit drug is contraindicated and cannot be used as gold standard for sensitivity and specificity determination.ObjectiveTo estimate the sensitivity and specificity of LTT in a clinically defined series of patients with DRESS.MethodsSome 41 patients diagnosed with DRESS were included in the study. The results of the algorithm of the Spanish Pharmacovigilance System were used as the standard for a correct diagnosis of drug causality. A standard LTT was performed with involved drugs in acute or recovery samples. A stimulation index (SI) 2 in at least one concentration except for beta-lactams (SI 3) and contrast media (SI 4) was considered positive. Contingency tables and ROC curves were used for analysis.ResultsSensitivity and specificity of LTT in the recovery phase of DRESS were 73% and 82%, respectively, whereas in the acute phase, they were only 40% and 30%, respectively. Comparison of skin tests and LTT confirmed a higher sensitivity and specificity of LTT in DRESS. LTT showed high sensitivity (S) and specificity (Sp) for anticonvulsants (S 100%, Sp 100%; P=.008), anti-TB drugs (S 87.5%, Sp 100%; P=.004), and beta-lactams (S 73%, Sp 100%; P=.001). ROC curves revealed that the best criteria for LTT positivity for all drugs are SI 2 in at least one concentration, increasing overall sensitivity to 80%, and for beta-lactams from 73% to 92%.Conclusions and clinical relevanceLTT is a good diagnostic tool for drug causality in DRESS, mainly when performed in the recovery phase.