Ide Minako, Kato Takeo, Nakata Masatoshi, Saito Keiko, Yoshida Takeshi, Awaya Tomonari, Heike Toshio
Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Brain Dev. 2015 Sep;37(8):825-8. doi: 10.1016/j.braindev.2014.12.010. Epub 2015 Jan 22.
Rufinamide, a triazole derivative, is a novel antiepileptic drug (AED) chemically unrelated to other current AEDs. Previous studies on pediatric epilepsy treatment with rufinamide have demonstrated a frequency of leukopenia as an adverse event of 0.5%, and there has been no report of the development of agranulocytosis. Here, we report a patient with Lennox-Gastaut syndrome (LGS) who developed agranulocytosis associated with fever and skin rash with rufinamide. To the best of our knowledge, this is the first reported case of agranulocytosis induced by rufinamide.
A 10-year-old boy with a history of herpes encephalitis at the age of 1 year developed LGS, and was administered rufinamide as add-on therapy to valproate, lamotrigine, and clonazepam because of difficulties in controlling tonic seizures. Eighteen days after initiation of rufinamide, agranulocytosis developed associated with high fever and skin rash, all of which resolved after withdrawal of rufinamide. Bone marrow aspiration demonstrated normocellular marrow with selective decrease of mature myeloid series, and suggested that agranulocytosis was not related to malignancy or serious infection.
This case suggests that rufinamide may induce the potentially serious adverse effect of agranulocytosis. Patients should be monitored for clinical signs of agranulocytosis and consideration should be given to routine blood count determination for early detection of this.
卢非酰胺是一种三唑衍生物，是一种新型抗癫痫药物（AED），在化学结构上与其他现有抗癫痫药物无关。先前关于卢非酰胺治疗小儿癫痫的研究表明，白细胞减少作为不良事件的发生率为0.5%，且尚无粒细胞缺乏症发生的报告。在此，我们报告1例患有Lennox-Gastaut综合征（LGS）的患者，其在使用卢非酰胺后出现了与发热和皮疹相关的粒细胞缺乏症。据我们所知，这是首例报道的由卢非酰胺引起的粒细胞缺乏症病例。
一名10岁男孩，1岁时患过疱疹性脑炎，后发展为LGS，由于难以控制强直发作，在丙戊酸、拉莫三嗪和氯硝西泮基础上加用卢非酰胺进行治疗。使用卢非酰胺18天后，出现了与高热和皮疹相关的粒细胞缺乏症，停用卢非酰胺后所有症状均缓解。骨髓穿刺显示骨髓细胞正常，但成熟髓系选择性减少，提示粒细胞缺乏症与恶性肿瘤或严重感染无关。
该病例提示卢非酰胺可能诱发潜在的严重不良反应粒细胞缺乏症。应监测患者粒细胞缺乏症的临床体征，并考虑定期进行血常规检查以早期发现该病。
