Mogami Yukiko, Takahashi Yukitoshi, Takayama Rumiko, Ohtani Hideyuki, Ikeda Hiroko, Imai Katsumi, Shigematu Hideo, Inoue Yushi
National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Japan.
Brain Dev. 2012 Jun;34(6):496-503. doi: 10.1016/j.braindev.2011.09.003. Epub 2011 Oct 11.
Patients with epilepsy after encephalitis/encephalopathy (EAE) often have refractory seizures, resulting in polytherapy with the risk of adverse reactions due to anti-epileptic drugs (AEDs). We focused on the characteristics of cutaneous adverse reaction (CAR). In this retrospective study, the medical records of 67 patients who were diagnosed as having EAE in our hospital were reviewed and the clinical characteristics were analyzed. Immunological biomarkers including cytokines, chemokines, granzyme B, soluble tumor necrosis factor receptor 1 (s-TNFR 1), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured in 22 patients. CARs attributed to AEDs were observed in 16 of 67 EAE patients (23.9%) (CAR group). High CAR rates were observed with phenytoin, lamotrigine, phenobarbital, and carbamazepine. Severe CARs were found in three of 67 patients (4.5%). The frequencies of CARs were significantly higher in patients with encephalitis onset older than five years of age. CAR occurred only in patients who had onset of EAE within 6 months after encephalitis. The durations from acute encephalitis to CARs were within one year for almost all AEDs, except lamotrigine. The proportion of patients with serumregulated on activation normal T cell expressed and secreted (RANTES) levels higher than the upper limit of normal range was significantly higher in CAR group than in non-CAR group. Patients in the early stage of EAE and patients with encephalitis onset older than five years of age may be at higher risk of CARs to AEDs, especially to phenytoin, lamotrigine, phenobarbital, and carbamazepine. RANTES may be a biomarker for susceptibility to CARs in EAE patients.
脑炎/脑病（EAE）后癫痫患者常出现难治性癫痫发作，导致多药联合治疗，存在抗癫痫药物（AEDs）不良反应风险。我们重点关注皮肤不良反应（CAR）的特征。在这项回顾性研究中，我们回顾了我院67例诊断为EAE患者的病历，并分析了其临床特征。对22例患者检测了包括细胞因子、趋化因子、颗粒酶B、可溶性肿瘤坏死因子受体1（s-TNFR 1）、基质金属蛋白酶-9（MMP-9）和金属蛋白酶组织抑制剂-1（TIMP-1）在内的免疫生物标志物。67例EAE患者中有16例（23.9%）观察到归因于AEDs的CARs（CAR组）。苯妥英、拉莫三嗪、苯巴比妥和卡马西平的CAR发生率较高。67例患者中有3例（4.5%）出现严重CARs。脑炎发病年龄大于5岁的患者中CARs的发生率显著更高。CAR仅发生在脑炎后6个月内发生EAE的患者中。除拉莫三嗪外，几乎所有AEDs从急性脑炎到CARs的持续时间均在1年内。CAR组血清中正常T细胞表达和分泌调节趋化因子（RANTES）水平高于正常范围上限的患者比例显著高于非CAR组。EAE早期患者和脑炎发病年龄大于5岁的患者可能发生AEDs所致CARs的风险更高，尤其是对苯妥英、拉莫三嗪、苯巴比妥和卡马西平。RANTES可能是EAE患者发生CARs易感性的生物标志物。
