Pharmacogenetics of cutaneous adverse drug reactions
Article first published online: 22 FEB 2011
© 2011 Japanese Dermatological Association
The Journal of Dermatology
Special Issue: SPECIAL ISSUE: Severe Adverse Cutaneous Drug Reaction (pages 215-260)
Volume 38, Issue 3, pages 246–254, March 2011
How to Cite
AIHARA, M. (2011), Pharmacogenetics of cutaneous adverse drug reactions. The Journal of Dermatology, 38: 246–254. doi: 10.1111/j.1346-8138.2010.01196.x
- Issue published online: 22 FEB 2011
- Article first published online: 22 FEB 2011
- Received 24 November 2010; accepted 24 November 2010.
- adverse drug reaction;
- drug-induced hypersensitivity syndrome;
- Stevens–Johnson syndrome;
- toxic epidermal necrolysis
Drug-induced hypersensitivity reactions are of major medical concern because they are associated with high morbidity and high mortality. In addition, individual patients' reactions are impossible to predict in each patient. In the field of severe cutaneous adverse drug reactions (cutaneous ADR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DHIS) or drug rash with eosinophilia and systemic symptoms (DRESS), major advances have recently been gained through studies of an association between HLA alleles and drug hypersensitivity induced by specific drugs. The results of these pharmacogenomic studies allow prediction of the risk of adverse reactions in patients treated with certain drugs, including carbamazepine and other aromatic antiepileptic drugs, allopurinol and abacavir. However, different ethnic populations show variations in the genetic associations. A strong association between carbamazepine-induced SJS/TEN and HLA-B*1502 has been found in Southeast Asian patients but not in Caucasian and Japanese patients. Moderate associations between aromatic amine anticonvulsants and other HLA alleles have been proposed in Japanese patients. In contrast, HLA-B*5801 was found to be associated with allopurinol-induced cutaneous ADR, including SJS/TEN and DIHS/DRESS, in Caucasian and Asian patients, including the Japanese. These differences may, at least in part, be due to the differences in allele frequency in different ethnic populations. This article reviews the progress in pharmacogenomics, associated mainly with carbamazepine and allopurinol in different ethnic populations. Pharmacogenetic screening based on associations between adverse reactions and specific HLA alleles helps to avoid serious conditions associated with drug hypersensitivity.