- 期刊
嚴重藥物過敏基因檢測HLA-B*1502臨床應用的實證醫學觀點
An Eevidence-Based Medicine Point of View Regarding Clinical Application of HLA-B*1502 Test and Severe Drug Hypersensitivity
摘要
藥物副作用是臨床上的一個重要課題，輕微的藥物過敏可能只是皮膚搔癢或紅疹，但嚴重時可能發生急性休克、肝腎衰竭及致命的「史帝文生-強生症候群」或「毒性表皮溶解壞死」等，造成嚴重的殘疾甚至死亡，在台灣由藥物引發的過敏及不良反應也非罕見。這些藥物過敏反應不僅對病人和家屬都帶來非常痛苦的經驗，也衍生了許多的醫療糾紛，耗費不少醫療及社會資源。隨著新科技的發展，服藥前先做基因檢測，瞭解有無嚴重藥物過敏體質，可以減少致命性藥害的發生。引發嚴重過敏的藥物或其發生率，在不同國家有些許差異，根據臨床統計最易引發國人嚴重藥物過敏反應的前二名藥物分別是：降尿酸藥（Allopurinol）和抗癲癇用藥（Carbamazepine）。本文就藥物過敏基因檢測之臨床應用的實證醫學觀點，就偵測之敏感度，特異度，陽性與陰性預測值，概似比等注意事項提出探討。
並列摘要
Drug hypersensitivity reaction is an important clinical issue. Mild maculopapular drug eruption is a common clinical problem. However, severe cutaneous adverse drug hypersensitivity reactions (shock, liver/kidney failure, Stevens-Johnson syndrome and toxic epidermal necrolysis) are associated with significant morbidity and mortality. Severe drug hypersensitivity reactions of patients also cause an increased financial burden for society and an increased number of lawsuits. Several recent studies have reported strong genetic associations between HLA alleles and susceptibility to severe drug hypersensitivity. The genetic associations can be drug or ethenity specific, such as HLA-B*1502 being associated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) and HLA-B*5801 with allopurinol-induced severe cutaneous adverse reactions are the leading drug in Taiwan. The high sensitivity and specificity of some genetic markers provides a plausible basis for developing tests to identify individuals at risk for drug hypersensitivity. Application of HLA genotyping as a screening tool before prescribing drug could be a valuable tool in preventing drug-induced SJS/TEN. The present article reviews the recent literature on the identification of human leukocyte antigen (HLA) alleles as major susceptible genes for drug hypersensitivity and discusses the clinical applications from an evidence-based point of view regarding sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio, and other points deserve of further discussion.