Department of Neurology, National Medical Center, Seoul, Korea.
Department of Neurology, Inha University Hospital, Incheon, Korea.
J Korean Med Sci. 2020 Feb 3;35(4):e17. doi: 10.3346/jkms.2020.35.e17.
Severe and life-threatening drug eruptions include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). One class of medications that has been highly associated with such drug eruptions is antiepileptic drugs (AEDs). We attempt to investigate drug eruptions associated with AEDs as a class, as well as with individual AEDs, in Korea.
We used the Korea Institute of Drug Safety and Risk Management - Korea Adverse Event Reporting System (KIDS-KAERS) database, a nationwide database of adverse events reports, between January 2008 and December 2017 to investigate the reporting count of all drug eruptions and calculated the ratio of DRESS/SJS/TEN reports for each AED.
Among a total of 2,942 reports, most were of rash/urticaria (2,702, 91.8%), followed by those of DRESS (109, 3.7%), SJS (106, 3.6%), and TEN (25, 0.85%). The common causative AEDs were lamotrigine (699, 23.8%), valproic acid (677, 23%), carbamazepine (512, 17.4%), oxcarbazepine (320, 10.9%), levetiracetam (181, 6.2%), and phenytoin (158, 5.4%). In limited to severe drug eruptions (DRESS, SJS, and TEN; total 241 reports), the causative AEDs were carbamazepine (117, 48.8%), lamotrigine (57, 23.8%), valproic acid (20, 8.3%), phenytoin (15, 6.3%), and oxcarbazepine (10, 4.2%). When comparing aromatic AED with non-aromatic AED, aromatic AEDs were more likely to be associated with severe drug eruption (aromatic AEDs: 204/1,793 versus non-aromatic AEDs: 37/1,149; OR, 3.86; 95% CI, 2.7-5.5). Death was reported in 7 cases; DRESS was the most commonly reported adverse event (n = 5), and lamotrigine was the most common causative AED (n = 5).
Although most cutaneous drug eruptions in this study were rash or urticaria, approximately 8% of reports were of severe or life-threatening adverse drug reactions, such as SJS, TEN, or DRESS. When hypersensitivity skin reactions occurred, aromatic AEDs were associated with 4 fold the risk of SJS/TEN/DRESS compared with non-aromatic AEDs. Our findings further emphasize that high risk AEDs should be prescribed under careful monitoring, and early detection and prompt interventions are needed to prevent severe complications.
严重且危及生命的药物疹包括药物反应伴嗜酸性粒细胞增多和全身症状（DRESS）、史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）。一类与这些药物疹高度相关的药物是抗癫痫药（AEDs）。我们试图在韩国调查 AED 类药物疹以及个别 AED 药物疹。
我们使用韩国药物安全与风险管理研究所-韩国不良事件报告系统（KIDS-KAERS）数据库，该数据库是一个全国性的不良事件报告数据库，涵盖 2008 年 1 月至 2017 年 12 月期间所有药物疹的报告数量，并计算了每种 AED 药物疹报告中 DRESS/SJS/TEN 的比例。
在总共 2942 份报告中，大多数是皮疹/荨麻疹（2702 份，91.8%），其次是 DRESS（109 份，3.7%）、SJS（106 份，3.6%）和 TEN（25 份，0.85%）。常见的致病 AED 是拉莫三嗪（699 份，23.8%）、丙戊酸（677 份，23%）、卡马西平（512 份，17.4%）、奥卡西平（320 份，10.9%）、左乙拉西坦（181 份，6.2%）和苯妥英（158 份，5.4%）。在仅限于严重药物疹（DRESS、SJS 和 TEN；共 241 份报告）中，致病 AED 是卡马西平（117 份，48.8%）、拉莫三嗪（57 份，23.8%）、丙戊酸（20 份，8.3%）、苯妥英（15 份，6.3%）和奥卡西平（10 份，4.2%）。当比较芳香族 AED 与非芳香族 AED 时，芳香族 AED 更易与严重药物疹相关（芳香族 AED：204/1793 与非芳香族 AED：37/1149；OR，3.86；95%CI，2.7-5.5）。报告了 7 例死亡病例；最常见的不良事件是 DRESS（n=5），最常见的致病 AED 是拉莫三嗪（n=5）。
尽管本研究中的大多数皮肤药物疹为皮疹或荨麻疹，但约 8%的报告为 SJS、TEN 或 DRESS 等严重或危及生命的药物不良反应。当发生过敏反应时，与非芳香族 AED 相比，芳香族 AED 与 SJS/TEN/DRESS 的风险增加了 4 倍。我们的研究结果进一步强调，应在密切监测下使用高危 AED，并需要早期发现和及时干预以预防严重并发症。
