淋巴细胞转化试验在药物相关性嗜酸性粒细胞增多和全身症状因果关系评估中的敏感性和特异性。
Sensitivity and specificity of the lymphocyte transformation test in drug reaction with eosinophilia and systemic symptoms causality assessment.
机构信息
Department of Allergy, La Paz University Hospital Health Research Institute (IdiPAZ), Madrid, Spain.
PIELenRed Consortium, Madrid, Spain.
出版信息
Clin Exp Allergy. 2018 Mar;48(3):325-333. doi: 10.1111/cea.13076. Epub 2018 Jan 19.
BACKGROUND
Drug 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.
OBJECTIVE
To estimate the sensitivity and specificity of LTT in a clinically defined series of patients with DRESS.
METHODS
Some 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.
RESULTS
Sensitivity 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 RELEVANCE
LTT is a good diagnostic tool for drug causality in DRESS, mainly when performed in the recovery phase.
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很复杂。淋巴细胞转化试验（LTT）在超过 50%的 DRESS 病例中呈阳性报告。然而，LTT 在 DRESS 中的敏感性和特异性尚未确定。再用致病药物进行挑战是禁忌的，不能作为敏感性和特异性确定的金标准。
目的
评估 LTT 在一组临床定义的 DRESS 患者中的敏感性和特异性。
方法
研究纳入了 41 名诊断为 DRESS 的患者。西班牙药物警戒系统算法的结果被用作药物因果关系正确诊断的标准。在急性或恢复期样本中，对涉及的药物进行标准 LTT。除非β-内酰胺（SI ≥3）和对比剂（SI ≥4），否则至少一个浓度的刺激指数（SI）≥2 被认为是阳性。使用列联表和 ROC 曲线进行分析。
结果
DRESS 恢复期 LTT 的敏感性和特异性分别为 73%和 82%，而急性期仅为 40%和 30%。皮肤试验和 LTT 的比较证实了 LTT 在 DRESS 中具有更高的敏感性和特异性。LTT 对抗惊厥药（S 100%，Sp 100%；P =.008）、抗结核药物（S 87.5%，Sp 100%；P =.004）和β-内酰胺类药物（S 73%，Sp 100%；P =.001）具有较高的敏感性（S）和特异性（Sp）。ROC 曲线显示，所有药物 LTT 阳性的最佳标准是至少一个浓度的 SI≥2，将总体敏感性提高到 80%，β-内酰胺类药物的敏感性从 73%提高到 92%。
结论和临床相关性
LTT 是 DRESS 药物因果关系的一种良好诊断工具，主要在恢复期进行。
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