title: Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan.
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. (Funded by the National Science Council of Taiwan and the Taiwan Drug Relief Foundation.).
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Pei
authors.initials: P
authors.lastname: Chen
authors.forename: Juei-Jueng
authors.initials: JJ
authors.lastname: Lin
authors.forename: Chin-Song
authors.initials: CS
authors.lastname: Lu
authors.forename: Cheung-Ter
authors.initials: CT
authors.lastname: Ong
authors.forename: Peiyuan F
authors.initials: PF
authors.lastname: Hsieh
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Yang
authors.forename: Chih-Ta
authors.initials: CT
authors.lastname: Tai
authors.forename: Shey-Lin
authors.initials: SL
authors.lastname: Wu
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Lu
authors.forename: Yung-Chu
authors.initials: YC
authors.lastname: Hsu
authors.forename: Hsiang-Yu
authors.initials: HY
authors.lastname: Yu
authors.forename: Long-Sun
authors.initials: LS
authors.lastname: Ro
authors.forename: Chung-Ta
authors.initials: CT
authors.lastname: Lu
authors.forename: Chun-Che
authors.initials: CC
authors.lastname: Chu
authors.forename: Jing-Jane
authors.initials: JJ
authors.lastname: Tsai
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Su
authors.forename: Sheng-Hsing
authors.initials: SH
authors.lastname: Lan
authors.forename: Sheng-Feng
authors.initials: SF
authors.lastname: Sung
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Lin
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Chuang
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Huang
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Pei-Joung
authors.initials: PJ
authors.lastname: Tsai
authors.forename: Hung-Ting
authors.initials: HT
authors.lastname: Liao
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Lin
authors.forename: Chien-Hsiun
authors.initials: CH
authors.lastname: Chen
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Chung
authors.forename: Shuen-Iu
authors.initials: SI
authors.lastname: Hung
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.forename: Chi-Feng
authors.initials: CF
authors.lastname: Chang
authors.forename: Luke
authors.initials: L
authors.lastname: Chen
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D002220:Carbamazepine / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D059910:HLA-B15 Antigen; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D013624:Taiwan; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D015235:HLA-B Antigens; C483536:HLA-B*15:02 antigen; D059910:HLA-B15 Antigen; D002220:Carbamazepine