奥卡西平皮肤不良反应与人类白细胞抗原基因相关性的研究进展

Progress on relation between human leukocyte antigen gene and oxcarbazepine induced cutaneous adverse drug reactions

奥卡西平是临床常用的新型抗癫痫药物,是卡马西平的结构类似物,常用作不能耐受卡马西平患者的替代治疗药物.尽管耐受性优于卡马西平,但其皮肤不良反应仍较常见,严重的不良反应常导致停药.与卡马西平相似,HLA-B﹡15：02基因多态性与奥卡西平诱发的严重皮肤不良反应相关,但与斑丘疹的发生不相关联.HLA-A﹡13：02、HLA-B﹡38：02和HLA-B﹡40：02等可能是与奥卡西平致斑丘疹相关的HLAⅠ类基因,而HLA-DRB1﹡04：03是第1个被发现的与奥卡西平斑丘疹相关的HLAⅡ类基因.目前奥卡西平皮肤不良反应的易感因素仍未完全明确,奥卡西平致斑丘疹与患者年龄、性别、体重和用药总剂量均不相关,而抗癫痫药物过敏史和非抗癫痫药物引发的过敏史可能为奥卡西平皮肤不良反应的危险因素.存在过敏史,特别是卡马西平过敏史的患者在使用奥卡西平前需要注意可能出现交叉过敏.对于出现斑丘疹的患者,在更换抗癫痫药物之前需进行HLA-B﹡15：02基因检测,而HLA-B﹡15：02阳性表达患者应避免使用芳香族类抗癫痫药物.

Oxcarbazepine（OXC）is a new antiepileptic drug developed through structural variation of carbamazepine and widely used for the patient who cannot tolerate carbamazepine. Although OXC has a lower risk of cutaneous adverse drug reactions（cADRs）than carbamazepine,it has been reported that OXC-induced cutaneous adverse drug reactions（OXC-cADRs）are prevalent and may lead to drug discontinua-tion. HLA-B﹡15：02 is associated with oxcarbazepine-induced SJS/TEN,but not maculopapule,which is similar to carbamazepine. In addition,HLA-A﹡13：02,HLA-B﹡38：02 and HLA-B﹡40：02 are HLAⅠtype genes which is related to oxcarbazepine-induced maculopapule（OXC-MPE）,and HLA-DRB1﹡04：03 was first HLA class Ⅱ gene found associated with OXC-MPE. The risk factor of OXC-cADRs is still not completely clear. Age,gender,weight and total dose of medication were not correlated with OXC-MPE. Allergy induced by antiepileptic drugs and non-antiepileptic drug induced allergy may be risk factors of OXC-cADRs. Attention should be paid to cross-allergic reactions before using oxcarbazepine for patients with a history of carbamazepine-induced allergy. Genetic test is not currently recommended in patients with maculopapule. Aromatic antiepileptic drugs should be avoided in patients with positive expression of HLA-B﹡15：02 gene.