Toxic Epidermal Necrolysis and Pharmacogenomics

For those who don't know what TEN is. I have a picture for you.

Toxic epidermal necrolysis (TEN) is a clinical syndrome characterized by severe exfoliative skin changes, erosive mucosal involvement, and potentially life-threatening multisystem involvement. Although this syndrome is considered uncommon, its true incidence may be underestimated because of a spectrum of manifestations that may lead to misdiagnosis of milder forms of the disease. TEN most commonly occurs in adults and is seen slightly more often in females. All races are affected

Yesterday, the FDA issued guidance for pharmacogenomic testing of patients taking the medication carbamazepine. What is this drug? It is used in prevention of seizures treatment of mood disorders and schizophrenia.

More than 100 drugs have been implicated. Medications most often involved are systemic sulfonamides and other antibiotics, allopurinol (Zyloprim), antiepileptics, and nonsteroidal antiinflammatory agents . The time from the first dose of a drug to the first cutaneous manifestation is usually 1 to 3 weeks

This medication has now been flagged as a cause of TEN that has preventable testing. In addition to the novel testing of an HLA haplotype, the drug is metabolized by CYP 3A4. CYP testing is available for ultrarapid metabolizer status. However, that is not what causes TEN. No one knows exactly what causes TEN for sure.

But the biggest problem is the 30-40% of people with this disease die from it or it's complications. Now wouldn't it be great if we could at least test a sub population at risk for this before giving this medication?

We can. From the FDA

Significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502, this allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians. Genetic tests for HLA-B*1502 are already available.

The Sherpa Says:

Ladies and gentlemen, I submit, we are now moving in to the era of personalized medicine. This test is yet another example. If 2007 was the year of the personal genome, I say 2008 will be the year of the personalized medical care. I hope that we can accurately represent the utility of these services. Wingedpig once again comments on the shortcomings. Also, where are the BRCA SNPs? Has Myriad's attorneys knocked on 23andMe's door yet?