Pharmacogenomics of Steven Johnson's Syndrome/ Toxic Epidermal Necrolysis
Steven Johnson's Syndrome/Toxic Epidermal Necrolysis Syndrome(SJS/TENS) is a serious cutaneous adverse events occurs in patients taking high risk drugs. The risks of SJS/TENS is vary depended on population, suggested the important role of host genetic in determination the occurrence of this adverse event. The number of SJS/TENS in Thailand is particularly high, catastrophic in some patients. Recently, a wave of genetic association studied identified HLA class I as an important risk factors for SJS/TENS
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Prevalence or rate of SJS/TENS in Thailand
Thai FDA data from 10 years surveillance suggest Thailand is among the top three countries in the world with SJS/TENS report. This might cause by the better detection system, but more likely cause might be the high prevalence of Carbamazepine induced SJS/TENS (Ranked no.2) and the Allopurinol induced SJS/TENS (yes, it induced SJS/TENS, not DRESS in Thailand). Annually, 700-800 SJS/TENS cases were reported to Thai FDA in the last ten years, the trends is stable despite awareness of the SJS/TENS problem in major hospitals in Thailand, especially the hospitals located in the Southern Part of Thailand.
Carbamazepine
HLA-B*1502 and Carbamazepine induced SJS/TENS
In 2004, researchers led by Prof. YT Chen in Academia Sinica, Taiwan discovered the association between Carbamazepine, an antiepileptic, induced SJS/TENS in Taiwan population.
This finding led to the waves of replication studies in other population, including Thais population. This association was confirmed in Thais population, form Central region and Northeastern regions, some of them are descendants of Chinese immigrants (Lohacharoen et al 2009, Tasaneeyakul et al 2010).
HLA-B*1502 prevalence in Asian Countries
HLA-B*1502 is common among Asian population, in some of Indonesian population, this allele is distributed with prevalence of nearly 20% (Yuriwulundari 2007). It is speculated that Southern Thais population should have about 10-15% prevalence of this HLA-B allele (Mahasirimongkol). In Japanese population, this allele is rare and it was not associated with CBZ-SJS/TENS in Japanese population.
Prospective testing for prevention of HLA-B*1502 associated toxic effect of Carbamazepine
Prospective trial in Taiwan had been investigated in Taiwanese population, due to the ethical reason, this study had been done based on comparison between the intervention (HLA-B*1502 tests) versus the historical control rate of SJS/TENS. This study is a prove of concept that HLA-B tests can prevent SJS/TENS from Carbamazepine (Chen et al 2011). This evidence provides the basis for implementation of this tests in other countries where HLA-B*1502 is common polymorphism in the populations.
Allopurinol
HLA-B*5801 and Allopurinol induced Severe Cutaneous Adverse Reaction (Allo-SCAR)
Prof. Yuan Tsong Chen led his team in Academia Sinica identified HLA-B*5801 associate with Allo-SCAR. This HLA-B allele is ubiquitous, it presents in 5-10% of general population, and help explain the global prevalent of this condition. Before 2010, alternatives to allopurinol is not as effective as allupurinol, an xanthine oxidase inhibiotr, in reducing blood uric acid, the most common indication of this medicaiton. Febuxostat is a newer hypouricemic agent that is good alternative for patients at risk of HLA-B*5801, no clinical study available for using feboxostat specific to the patients with HLA-B*5801, but it is likely that the side effects are not overlapped between these two medication.
Nevirapine
References
“Personalized Medicine for HLA-Associated Drug-Hypersensitivity Reactions: Carbamazepine-induced SJS/TEN & HLA-B*1502.”
http://www.medscape.com/viewarticle/730330_3.
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