Lanctôt K L, Ghajar B M, Shear N H, Naranjo C A
Psychopharmacology Research Program, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
J Clin Pharmacol. 1994 Dec;34(12):1228-33. doi: 10.1002/j.1552-4604.1994.tb04736.x.
The differential diagnosis of idiosyncratic adverse drug reactions (ADRs) is difficult because symptoms are seldom pathognomonic. The authors compared the performance of two new diagnostic aids in the differential diagnosis of 27 cases of skin reactions associated with sulfonamide therapy. One test, the Bayesian Adverse Reaction Diagnostic Instrument (BARDI), calculates the posterior probability (PsP) of a drug being the etiology of an idiosyncratic ADR. The other, the lymphocyte toxicity assay (LTA), is a biochemical test that determines the percent of cell death because of toxic metabolites of a drug. Cases were assessed independently and blindly by BARDI and then the LTA. Skin reactions consisted of 19 exanthematous eruptions, 2 vasculitis, 1 erythema multiforme, and 5 urticarial rashes. BARDI indicated that the drug was very likely associated with 20 adverse events (PsP = 0.59 to 0.99); and unlikely to have caused 7 (PsP = 0.02 to 0.38). The LTA showed that 19 patients (70%) were test positive, and 8 were test negative. Comparing BARDI to LTA showed that BARDI had 79% sensitivity and 67% accuracy, but only 38% specificity. However, when the results of the LTA were incorporated into the calculation of the PsP based on this comparison, BARDI indicated that the drug was very likely associated with 18 reactions (PsP = 0.61 to 0.99) and unlikely to have caused 9 reactions (PsP = 0.003 to 0.47). The agreement increased from 67% to 96%. These findings indicate that the accuracy of diagnosis of idiosyncratic ADRs improved when the results of BARDI and LTA were combined. These findings also crossvalidate the results obtained by using BARDI.
特异质性药物不良反应（ADR）的鉴别诊断很困难，因为症状很少具有诊断特异性。作者比较了两种新的诊断辅助方法在27例与磺胺类药物治疗相关的皮肤反应鉴别诊断中的表现。一种测试是贝叶斯不良反应诊断工具（BARDI），它计算药物作为特异质性ADR病因的后验概率（PsP）。另一种是淋巴细胞毒性试验（LTA），这是一种生化试验，可确定因药物毒性代谢产物导致的细胞死亡百分比。由BARDI和LTA分别独立且盲法评估病例。皮肤反应包括19例皮疹、2例血管炎、1例多形红斑和5例荨麻疹。BARDI表明，药物很可能与20例不良事件相关（PsP = 0.59至0.99）；不太可能导致7例（PsP = 0.02至0.38）。LTA显示，19例患者（70%）检测呈阳性，8例检测呈阴性。将BARDI与LTA比较发现，BARDI的敏感性为79%，准确性为67%，但特异性仅为38%。然而，基于该比较将LTA结果纳入PsP计算时，BARDI表明药物很可能与18例反应相关（PsP = 0.61至0.99），不太可能导致9例反应（PsP = 0.003至0.47）。一致性从67%提高到96%。这些发现表明，将BARDI和LTA的结果结合时，特异质性ADR的诊断准确性得到提高。这些发现也对使用BARDI获得结果进行了交叉验证。
