ANTICONVULSANT HYPERSENSITIVITY SYNDROME - INVITRO ASSESSMENT OF RISK
ANTICONVULSANT HYPERSENSITIVITY SYNDROME - INVITRO ASSESSMENT OF RISK
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DOI：
10.1172/jci113798
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发表时间：
1988-12-01
影响因子：
15.9
通讯作者：
SPIELBERG, SP
中科院分区：
文献类型：
--
作者：
SHEAR, NH;SPIELBERG, SP
芳香族抗惊厥药（苯妥英、苯巴比妥和卡马西平）的氧化芳烃代谢物可能参与超敏反应的发病机制。我们通过将体外淋巴细胞暴露于小鼠肝微粒体系统产生的药物代谢物，研究了 53 名对抗惊厥药物具有临床敏感性的患者。当细胞毒性（死细胞百分比）比对照平均结果高出 3 个标准差时，对每种药物（苯妥英，n = 34；苯巴比妥，n = 22；卡马西平，n = 25）进行体外再激发，证实了超敏反应的诊断。注意到药物之间的交叉反应。接受全部三种抗惊厥药物治疗的 10 名患者中，有 7 名出现不良反应。对所有三种药物进行体外测试的 50 名患者中，有 40 名患者每种药物均呈阳性。抗惊厥药物之间的不良反应无法区分。皮疹（87%）、发热（94%）、肝炎（51%）和血液学异常（51%）是每种药物的常见临床特征。 62% 的反应涉及两个以上的器官。来自患者父母的细胞表现出的体外毒性介于对照和患者的值之间。体外测试可以帮助诊断抗惊厥药物的过敏反应。来自患者的细胞也可用于前瞻性个体化治疗，以降低不良反应的风险。主要抗惊厥药之间的交叉反应很常见，在决定替代疗法之前应考虑到。
Arene oxide metabolites of aromatic anticonvulsants (phenytoin, phenobarbital, and carbamazepine) may be involved in the pathogenesis of hypersensitivity reactions. We investigated 53 patients with clinical sensitivity to anticonvulsants by exposing their lymphocytes in vitro to drug metabolites generated by a murine hepatic microsomal system. The diagnosis of a hypersensitivity reaction was corroborated by in vitro rechallenge for each drug (phenytoin, n = 34; phenobarbital, n = 22; carbamazepine, n = 25) when cytotoxicity (% dead cells) exceeded 3 SD above the mean result for controls. Cross-reactivity among the drugs was noted. 7 out of 10 patients who had received all three anticonvulsants had adverse reactions to each. 40 out of 50 patients tested to all three drugs in vitro were positive to each. Adverse reactions were indistinguishable among anticonvulsants. Skin rash (87%), fever (94%), hepatitis (51%), and hematologic abnormalities (51%) were common clinical features of each drug. 62% of reactions involved more than two organs. Cells from patients'' parents exhibited in vitro toxicity that was intermediate between values for controls and patients. In vitro testing can help diagnose hypersensitivity to anticonvulsants. Cells from patients may also be used for prospective individualization of therapy to decrease risk of adverse reaction. Cross-reactivity among the major anticonvulsants is common and should be considered before deciding on alternative therapy.