Which means that SJS/TEN should be almost entirely preventable.
As Wasun Chantratita from Mahidol University puts it, it's “the low-hanging fruit of genomic medicine.” To deal with it, you don't need to edit genes, or turn to stem cells, or prescribe drugs that target mutations in a patient's DNA. You just need to screen people for the risky variants and withhold the triggering drugs.
But, as is often the case, things aren't that straightforward. The case of SJS/TEN shows how the promise of genomic medicine, even in simple cases, can be stymied by mundane obstacles.
Back in 2002, SJS/TEN was a regular feature in the dermatology ward of Taiwan's Chang Gung Memorial Hospital. “Two patients were admitted every week and this disease was supposedly ‘rare,’” recalls Wen-Hung Chung, then a newly minted attending physician. Chung noticed that everyone who got the condition had taken either carbamazepine, used to treat epilepsy and seizures, or allopurinol, used to treat gout. But he didn't know why some people absorbed these medicines calmly, while others reacted disastrously.
To Chung's wife, the immunologist Shuen-Iu Hung, the condition looked like some kind of berserk immune response, and the duo wondered if some patients had genes that predisposed them to such violent reactions. The HLA genes were the most likely candidates. These make proteins that grab suspicious molecules and brandish them for the immune system to inspect. They come in a vast smorgasbord of variants, each one shaped to recognize a different molecule. Perhaps some people have HLA variants that grab onto drugs, triggering misplaced immune assaults. And since the drugs typically diffuse throughout a patient's body, these assaults lead to systemic inflammation.
By sequencing the HLA genes in their patients, Chung and Hung found one variant—HLA-B*15:02—that shows up in every single person who developed SJS/TEN after taking carbamazepine, compared to just 3 percent of patients who tolerated the drug. That result, published in 2004, became a classic example of pharmacogenomics—the study of how our genes affect our responses to drugs.
More examples followed. Chung and other scientists soon identified many other drugs that trigger SJS/TEN, including anti-HIV medications like abacavir and nevirapine, and anti-convulsants like phenytoina and lamotrigine. Each drug is associated with its own particular risky HLA variants.
The obvious solution would be to phase out these drugs and, to an extent, that's happened. In Taiwan, carbamazepine prescriptions have fallen by around 70 percent in the last decade, as doctors have swapped to a safer second generation of anti-epileptics. But since these newer drugs are also more expensive, some countries like Thailand have found it harder to make the switch. “In developed countries, you’d use the new drug first,” says Chantratita. “But in our country, the majority of medications are old drugs.”