Schlienger R G, Shapiro L E, Shear N H
Division of Clinical Pharmacology, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada.
Epilepsia. 1998;39 Suppl 7:S22-6. doi: 10.1111/j.1528-1157.1998.tb01681.x.
We systematically reviewed and analyzed published and unpublished cases of Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN) associated with lamotrigine (LTG) therapy to identify characteristics of these reactions.
We performed a MEDLINE search (January 1985 to April 1998) and citation tracking for published reports. In addition, reports were requested from the Uppsala Monitoring Centre of the World Health Organization (WHO). Published and WHO cases of LTG-associated SJS or TEN were included if the causal relationship was assessed as either possible, probable, or definite.
We identified a total of 57 cases (43 cases of SJS, 14 cases of TEN), of which 13 (23%) were published. Cases in the SJS group were significantly younger than in the TEN group (21 years vs. 31 years). The median time to onset (17 days for SJS and TEN) and the median dosage at onset (50 mg vs. 87.5 mg) for SJS and TEN did not differ significantly. Concomitant use of valproate (VPA) was reported in 74% of the SJS cases and 64% of the TEN cases. In three cases, TEN was the cutaneous manifestation of the antiepileptic drug hypersensitivity syndrome (AHS).
The main features of severe cutaneous drug reactions, such as dosage, onset, and concomitant VPA use, do not differ in patients with LTG-induced SJS or TEN. SJS or TEN may also be the cutaneous manifestations of LTG-induced AHS. Further epidemiologic studies are needed to identify the incidence of severe LTG-induced cutaneous adverse reactions and the relative risk compared with other AEDs.
我们系统回顾并分析了已发表和未发表的与拉莫三嗪（LTG）治疗相关的史蒂文斯-约翰逊综合征（SJS）或中毒性表皮坏死松解症（TEN）病例，以确定这些反应的特征。
我们对1985年1月至1998年4月期间发表的报告进行了MEDLINE检索和引文追踪。此外，还向世界卫生组织（WHO）乌普萨拉监测中心索取报告。如果因果关系被评估为可能、很可能或肯定，则纳入已发表的以及WHO的与LTG相关的SJS或TEN病例。
我们共识别出57例病例（43例SJS，14例TEN），其中13例（23%）已发表。SJS组的病例比TEN组的病例明显年轻（21岁对31岁）。SJS和TEN的中位发病时间（均为17天）以及发病时的中位剂量（分别为50毫克和87.5毫克）差异不显著。74%的SJS病例和64%的TEN病例报告了同时使用丙戊酸盐（VPA）。在3例病例中，TEN是抗癫痫药物超敏反应综合征（AHS）的皮肤表现。
LTG诱发的SJS或TEN患者中，严重皮肤药物反应的主要特征，如剂量、发病情况以及同时使用VPA等方面并无差异。SJS或TEN也可能是LTG诱发的AHS的皮肤表现。需要进一步的流行病学研究来确定严重LTG诱发的皮肤不良反应的发生率以及与其他抗癫痫药物相比的相对风险。
