|Title:||Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan||Authors:||PEI-JER CHEN
|Issue Date:||2011||Publisher:||Massachussetts Medical Society||Journal Volume:||364||Journal Issue:||12||Start page/Pages:||1126-1133||Source:||New England Journal of Medicine||Abstract:||
BACKGROUND: Carbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA B*1502 allele. We sought to prevent carbamazepine-induced SJS-TEN by using HLA-B*1502 screening to prospectively identify subjects at genetic risk for the condition. METHODS: From 23 hospitals in Taiwan, we recruited 4877 candidate subjects who had not taken carbamazepine. We genotyped DNA purified from the subjects' peripheral blood to determine whether they carried the HLA-B*1502 allele. Those testing positive for HLA-B*1502 (7.7% of the total) were advised not to take carbamazepine and were given an alternative medication or advised to continue taking their prestudy medication; those testing negative (92.3%) were advised to take carbamazepine. We interviewed the subjects by telephone once a week for 2 months to monitor them for symptoms. We used the estimated historical incidence of SJS-TEN as a control. RESULTS: Mild, transient rash developed in 4.3% of subjects; more widespread rash developed in 0.1% of subjects, who were hospitalized. SJS-TEN did not develop in any of the HLA-B*1502-negative subjects receiving carbamazepine. In contrast, the estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P<0.001). CONCLUSIONS: The identification of subjects carrying the HLA-B*1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN. Copyright ? 2011 Massachusetts Medical Society.
|ISSN:||0028-4793||DOI:||10.1056/NEJMoa1009717||metadata.dc.subject.other:||carbamazepine; gabapentin; HLA B antigen; HLA B1502 antigen; imipramine; lamotrigine; naproxen; prednisolone; unclassified drug; adult; antigen detection; article; bipolar disorder; blister; clinical article; dizziness; drug eruption; drug fever; drug induced disease; epilepsy; fatigue; female; gastrointestinal disease; gene frequency; genetic risk; genetic screening; genotype; human; hypersensitivity; insomnia; maculopapular rash; male; mental disease; mouth ulcer; neuralgia; neuropathic pain; prevalence; priority journal; pruritus; screening test; sore throat; Stevens Johnson syndrome; Taiwan; tinnitus; toxic epidermal necrolysis; treatment duration; urticaria
|Appears in Collections:||臨床醫學研究所|
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