Department of Pain Medicine, Singapore General Hospital, Singapore.
Anesthesiology and Perioperative Sciences Academic Clinical Program, Duke-NUS Graduate Medical School.
Pharmacogenet Genomics. 2024 Jul 1;34(5):154-165. doi: 10.1097/FPC.0000000000000531. Epub 2024 Mar 22.
This umbrella review was conducted to summarize the association between HLA*1502 allele with antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Pubmed, Scopus and EMBASE were searched for eligible reviews in May 2023. Two authors independently screened titles and abstracts and assessed full-text reviews for eligibility. The quality of meta-analyses and case-control studies was appraised with Assessing the Methodological Quality of Systematic Reviews 2 and Newcastle-Ottawa Scale, respectively. Narrative summaries of each antiepileptic drug were analyzed. Preestablished protocol was registered on the International Prospective Register of Systematic Reviews Registry(ID: CRD42023403957).
Included studies are systematic reviews, meta-analyses and case-control studies evaluating the association of HLA-B*1502 allele with the following antiepileptics. Seven meta-analyses for carbamazepine, three meta-analyses for lamotrigine (LTG), three case-control studies for oxcarbazepine, nine case-control studies for phenytoin and four case-control studies for phenobarbitone were included. The findings of this umbrella review suggest that there is a strong association between HLA-B-1502 with SJS/TEN for carbamazepine and oxcarbazepine and a milder association for lamotrigine and phenytoin.
In summary, although HLA-B1502 is less likely to be associated with phenytoin or lamotrigine-induced SJS/TEN compared to carbamazepine-induced SJS/TEN, it is a significant risk factor that if carefully screened, could potentially reduce the development of SJS/TEN. In view of potential morbidity and mortality, HLA-B1502 testing may be beneficial in patients who are initiating lamotrigine/phenytoin therapy. However, further studies are required to examine the association of other alleles with the development of SJS/TEN and to explore the possibility of genome-wide association studies before initiation of treatment.
本伞式综述旨在总结 HLA*1502 等位基因与抗癫痫药诱导的史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）的相关性。
于 2023 年 5 月在 Pubmed、Scopus 和 EMBASE 上检索合格的综述。两位作者独立筛选标题和摘要，并评估全文综述的纳入标准。使用评估系统评价方法学质量 2 版（AMSTAR 2）和纽卡斯尔-渥太华量表（Newcastle-Ottawa Scale）分别评估荟萃分析和病例对照研究的质量。对每种抗癫痫药物进行叙述性总结分析。预先制定的方案已在国际前瞻性系统评价注册库（ID：CRD42023403957）上注册。
纳入的研究是评估 HLA-B*1502 等位基因与以下抗癫痫药相关性的系统评价、荟萃分析和病例对照研究。纳入了 7 项卡马西平的荟萃分析、3 项拉莫三嗪（LTG）的荟萃分析、3 项奥卡西平的病例对照研究、9 项苯妥英的病例对照研究和 4 项苯巴比妥的病例对照研究。本伞式综述的结果表明，HLA-B-1502 与卡马西平、奥卡西平所致 SJS/TEN 密切相关，与拉莫三嗪和苯妥英所致 SJS/TEN 相关程度较轻。
总之，与卡马西平引起的 SJS/TEN 相比，HLA-B1502 与苯妥英或拉莫三嗪引起的 SJS/TEN 的相关性较低，但它是一个重要的危险因素，如果经过仔细筛查，可能会降低 SJS/TEN 的发生风险。鉴于潜在的发病率和死亡率，在开始拉莫三嗪/苯妥英治疗时，HLA-B1502 检测可能对患者有益。然而，还需要进一步研究以检验其他等位基因与 SJS/TEN 发生的相关性，并在开始治疗前探索全基因组关联研究的可能性。
