Genetic predisposition of life-threatening antiepileptic-induced skin reactions.
BACKGROUND
Recent advances in pharmacogenetic studies have uncovered increasingly more genes that predispose individuals to adverse drug reactions. Aromatic antiepileptic drugs (AEDs) are a frequent cause of severe cutaneous adverse reactions (SCAR). A strong genetic association between HLA-B*1502 and carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) has been shown in Han Chinese patients.


METHODS
This article reviews and updates genetic information associated with CBZ and other AEDs causing SCAR in different ethnic populations.


RESULTS
Independent studies from different countries confirmed that patients carrying the HLA-B*1502 are at high risk of SJS/TEN when exposed to CBZ. The US FDA and similar regulatory agencies in Canada and Taiwan have updated the CBZ drug label to include the genetic information. Available data also suggest that HLA-B*1502 is a risk allele for SJS/TEN caused by other aromatic AEDs with a similar structure to CBZ.


CONCLUSIONS
Screening for HLA-B*1502 allele before starting treatment with CBZ is justified in patients from high-risk populations as recommended by regulatory agencies. Similar chemicals should also be avoided in individuals who test positive for HLA-B*1502.
Chung
Wen-Hung
WH
Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Department of Dermatology, Tung-Hwa North Road, Taipei 10507, Taiwan.
Hung
Shuen-Iu
SI
Chen
Yuan-Tsong
YT
D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects*; D004348:Drug Labeling; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000009:adverse effects*; D059910:HLA-B15 Antigen; D006801:Humans; D044469:Racial Groups / Q000235:genetics; D012871:Skin Diseases / Q000139:chemically induced / Q000235:genetics; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced* / Q000235:genetics*
D000927:Anticonvulsants; D015235:HLA-B Antigens; C483536:HLA-B*15:02 antigen; D059910:HLA-B15 Antigen; D002220:Carbamazepine