Researchers in Taiwan have delved into the genetics of Stevens Johnson Syndrome for answers about this rare but serious drug reaction. Their research may shed some light on a major risk factor for developing SJS from drugs like Onfi and Dilatin.

Stevens Johnson Syndrome is a type of allergic reaction. With allergic reactions, the immune system malfunctions and attacks the patient’s own body the way it would normally attack viruses or bacteria.

In the case of Stevens Johnson Syndrome, the immune system attacks the largest organ of the body, the skin. SJS symptoms start with fever, chills, and muscle aches, but it rapidly escalates to a debilitating rash with sores, blisters and ulcers. SJS symptoms can spread to the eyes and internal organs, causing blindness and death.

The most severe cases of SJS can become a related disorder called Toxic Epidermal Necrolysis, or TEN. TEN patients’ skin dies and sloughs off in patches, leaving burn-like wounds. The mortality rate for TEN is higher than some strains of the Ebola virus. SJS and TEN are both relatively rare, which makes it hard for medical researchers to study it. Despite this, nearly all cases of SJS and TEN can be traced to exposures to drugs like Onfi and Dilantin.

In this study, researchers performed a case-control study. In this type of study, researchers identify a group of patients with a disease, in this case, Stevens Johnson Syndrome. Researchers then find a very similar group of people who do not have the disease and compare them to try and find risk factors.

In this case, the researchers took DNA samples from 61 people who developed SJS and TEN from a drug called Dilantin, 78 people who had a milder autoimmune drug reaction, 130 people who had tolerated Dilantin with no reaction, and 3,655 people from the general population.

Researchers found that patients that developed SJS or TEN from Dilantin had changes to a certain gene. In a healthy person, a gene called CYP2C holds the design for an enzyme. Cells in the liver produce this enzyme and use it to break down about 5 percent to 10 percent of known drugs.

This includes both Onfi (clobazam) and Dilantin (pheytoin). In people who developed SJS or TEN from Dilantin had various “nonsense mutations” to this gene. This means that a mutation in their CYP2C genes effectively derails the gene and keeps it from producing a working version of the enzyme.

While this study focused on patients that took Dilantin, the same CYP2C enzyme also breaks down Onfi in the body, meaning that this same type of mutation could have a similar impact on patients taking this drug. In fact, the FDA issued a Safety Announcement in late 2013 that stated the federal agency had received case reports of SJS in patients taking Onfi, including cases that were fatal and caused permanent blindness.