Pharmacogenetics of toxic epidermal necrolysis.
BACKGROUND
Toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS) are two of the most severe drug-induced cutaneous reactions. Advances in genome technologies have allowed researchers to identify genetic markers associated with this drug-associated event and these have provided a potential tool for prevention.


METHODS
Current updates of genetic biomarkers that have been identified as being associated with TEN/SJS induced by several drugs, and the associations of these markers in different populations, are discussed.


RESULTS
The strong association of HLA-B*1502 and carbamazepine (CBZ)-induced TEN/SJS have been reported by several independent studies. This association was mostly observed in patients of Southeast Asian ancestry; it was not observed in populations with low HLA-B*1502 allele frequency. Studies also suggest that drugs with a similar chemical structure to CBZ might also induce TEN/SJS in patients with HLA-B*1502. In addition to CBZ, HLA-B*5801 was also found to associate with allopurinol-induced TEN/SJS. This strongly suggests that the associations of these markers with TEN/SJS are drug specific.


CONCLUSIONS
The strong association between CBZ and HLA-B*1502 has prompted the US Food and Drug Administration to update the label for CBZ to include genetic information and to recommend genetic testing before prescribing CBZ. Patients with Asian ancestry or who are from regions prevalent in HLA-B*1502 should be screened before CBZ treatment.
Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, 11529 Taipei, Taiwan.
Ming Ta Michael
MT
Lee
Shuen-Iu
SI
Hung
Chun-Yu
CY
Wei
Yuan-Tsong
YT
Chen
D064420:Drug-Related Side Effects and Adverse Reactions; D005787:Gene Frequency; D005805:Genes, MHC Class I; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology
D005819:Genetic Markers; D015235:HLA-B Antigens