Dilantin Stevens-Johnson Syndrome Risk May Have Genetic Link: Study

New research suggests that genetics may play a role in the risk of Stevens-Johnson syndrome associated with the antiepileptic drug Dilantin, which may provide a means of predicting which users face the greatest risk of suffering the disfiguring and potentially life-threatening skin reaction associated with several medications. 

In a study published in the Journal of the American Medical Association (JAMA), researchers from Taiwan identified one gene variant that is crucial in determining whether a Dilantin side effects cause users to develop Stevens-Johnson syndrome or other severe skin reactions.

The findings raise questions about whether genetics may provide a key in better understanding the Stevens-Johnson syndrome reaction risk, potentially helping individuals avoid the serious condition.

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Stevens-Johnson Syndrome ( SJS) is a painful and debilitating reaction, which cause the skin to burn, producing blisters, severe rashes and the skin may begin to separate from the body. When the skin lesions from SJS affect more than 30% of the body, the condition is typically referred to as toxic epidermal necrolysis (TEN). Treatment in a hospital Intensive Care Unit (ICU) or Burn Unit is often required, and the conditions can be fatal in many cases.

Side effects of Dilantin and several other medications have been linked to the development of SJS In November 2008, the FDA issued a warning about the potential risk of Stevens-Johnson Syndrome from Dilantin and Phenytek, but a number of product liability lawsuits have been filed against various drug makers over failure to adequately warn about the risk of the severe skin reaction.

In this new study, researchers conducted a case-control trial involving 105 cases from 2002-2014 involving patients who took Dilantin and suffered severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, the related toxic epidermal necrolysis, and drug reactions with eosinophilia and systemic symptoms as well. They also looked at 130 patients who tolerated Dilantin well and a control of 3,655 subjects not on the drug from Taiwan, Japan, and Malaysia.

Suspecting a genetic link, the researchers used data from a genome-wide association study. They found that those with certain variants of the CYP2C gene appeared to be more likely to suffer severe skin reaction when taking Dilantin.

“This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous reactions,” the study’s authors concluded. “These findings may have potential to improve the safety profile of phenytoin in clinical practice and offer the possibility of prospective testing for preventing phenytoin-related severe cutaneous reactions. More research is required to replicate the genetic association in different populations and to determine the test characteristics and clinical utility.”

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