Preventing Stevens-Johnson Syndrome from Carbamazepine with Genetic Testing

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• Asian Ancestry and SJS Risk
• The HLA-B*1502 Gene Mutation
• Symptoms of Stevens-Johnson Syndrome
• Clinical Trial Breakthrough in Taiwan
• The Genetic Testing Solution
• FDA Warning and Public Health Impact
• Precision Medicine in Action
• Full Transcript

Asian Ancestry and SJS Risk

Carbamazepine, sold under brand names like Tegretol, Carbatrol, and Equetro, is a widely prescribed anti-seizure medication. Dr. Esteban Burchard, MD, highlights a critical finding: individuals of Asian descent possess a special genetic susceptibility to a severe side effect from this drug. This risk is particularly high for people from China, Singapore, Malaysia, Taiwan, and Thailand. The side effect in question is Stevens-Johnson syndrome (SJS), a potentially fatal condition.

The HLA-B*1502 Gene Mutation

The specific genetic factor responsible for this increased risk is a mutation known as the HLA-B*1502 allele. This gene is located on the HLA locus, a region of DNA important for immune system function. Dr. Esteban Burchard, MD, explains that possessing this allele is a powerful predictor of an adverse reaction. The presence of this mutation does not cause disease on its own, but when a carrier takes carbamazepine, it triggers a catastrophic immune response.

Symptoms of Stevens-Johnson Syndrome

Stevens-Johnson syndrome and its more severe form, toxic epidermal necrolysis (TEN), are life-threatening skin reactions. Dr. Burchard describes the condition as one where "the skin of patients peels off on the outside and on the inside." This severe skin sloughing leads to massive fluid loss, pain, and a high risk of fatal infection, making it a major medical emergency that is extremely difficult to treat.

Clinical Trial Breakthrough in Taiwan

A pivotal clinical trial conducted in Taiwan was responsible for this discovery. Dr. Esteban Burchard, MD, notes that this research was crucial because clinical trials are often not done in diverse populations. The study, which was later published in the prestigious journal *Nature*, successfully identified the HLA-B*1502 allele as the genetic marker that predisposes Han Chinese and other Asian populations to a 4,000-fold increased risk of developing SJS from carbamazepine.

The Genetic Testing Solution

The implementation of preemptive genetic testing has been a monumental success in preventing this adverse drug reaction. Dr. Esteban Burchard, MD, emphasizes that the test itself is remarkably accessible and inexpensive, costing only about 10 cents. By screening patients of Asian ancestry for the HLA-B*1502 allele before prescribing carbamazepine, doctors can entirely avoid cases of SJS, choosing a safer alternative anti-epileptic medication instead.

FDA Warning and Public Health Impact

The findings from the Taiwan trial had a significant public health impact, leading to action by the U.S. Food and Drug Administration (FDA). The FDA issued a black box warning—the agency's strongest safety alert—on carbamazepine packaging. This warning explicitly states that individuals of Asian descent must be genetically tested for the HLA-B*1502 allele before initiating treatment with the drug to mitigate the risk of Stevens-Johnson syndrome.

Precision Medicine in Action

This case is a textbook example of precision medicine, where treatment is tailored to an individual's genetic makeup. Dr. Esteban Burchard, MD, strongly advocates for this approach, stating that if his child needed carbamazepine, he would demand the test. It demonstrates how a simple, cheap genetic test can prevent a life-threatening outcome, transforming patient safety for a common medication and underscoring the critical importance of considering genetic ancestry in diagnosis and treatment planning.

Full Transcript

Dr. Esteban Burchard, MD: Tegretol side effects in Asians include Stevens-Johnson syndrome, a potentially fatal skin sloughing condition. One mutation increases the risk of having this side effect of Tegretol, or carbamazepine, by 4,000 times. The genetic test costs 10 cents.

Carbamazepine is a widely prescribed anti-seizure medication with brand names like Carbatrol, Equetro, and Tegretol. People of Asian descent have a special gene mutation called the HLA-B*1502 allele, which predicts a high risk of side effects from Tegretol.

People from China, Singapore, Malaysia, Taiwan, and Thailand are at high risk for Stevens-Johnson syndrome. This is precision medicine in action.

Dr. Anton Titov, MD: How does individual genetic DNA ancestry influence the risk of getting certain diseases? Genetic DNA ancestry influences the probability of serious side effects from carbamazepine, a common anti-epilepsy medication. Please talk about that.

Dr. Esteban Burchard, MD: We have a similar situation with carbamazepine, a common medicine to treat epilepsy in children and one of the most commonly prescribed medicines for epilepsy. Clinical trials are usually not done in people of non-European DNA ancestry because they are more difficult to conduct.

A clinical trial was done in Taiwan on people of Asian descent. Scientists found a gene on the HLA locus that predisposes a person to a severe side effect of carbamazepine known as Stevens-Johnson syndrome, a life-threatening condition.

The skin of patients with Stevens-Johnson syndrome peels off on the outside and on the inside. This gene is common in people of Asian DNA ancestry, so if you have Asian DNA ancestry, you are 4,000 times more likely to have Stevens-Johnson syndrome as a side effect of epilepsy treatment with carbamazepine.

Han Chinese are at high risk of SJS and Toxic Epidermal Necrolysis. As a result of this clinical trial, patients with epilepsy throughout Asia who plan to receive carbamazepine must be genetically tested. This genetic carbamazepine test has stopped all cases of Stevens-Johnson syndrome in Asian patients with epilepsy because it is done before carbamazepine is prescribed.

Dr. Anton Titov, MD: This is a major accomplishment. Stevens-Johnson syndrome is a potentially fatal disease and a major dramatic event in a patient's life that is difficult to treat. Carbamazepine is often prescribed to patients with epilepsy around the world.

Dr. Esteban Burchard, MD: Yes, this genetic test is also important because a patient may not be entirely of Asian descent but could have Asian DNA ancestry in that particular gene, predisposing them to Stevens-Johnson syndrome. Then such a patient has a 4,000-fold increase in the risk of developing Stevens-Johnson syndrome when taking carbamazepine medication to treat epilepsy. This clinical trial has had a major public health impact.

That scientific clinical trial was published in the journal "Nature" and has significant public health impact. The US FDA wrote a warning in the instructions that come with carbamazepine pills, stating that if you are Asian or have Asian ancestry at that particular genetic location, you must have this genetic test before taking carbamazepine.

Dr. Anton Titov, MD: Can patients buy this genetic test? Is it expensive?

Dr. Esteban Burchard, MD: Yes, patients can purchase this genetic test, and it is cheap—it costs 10 cents. So a patient prescribed carbamazepine can buy this test for 10 cents and find out if they have a 4,000-fold increased risk of a potentially fatal side effect. This is personalized medicine.

If my child was going to need carbamazepine, I would demand to do this genetic test. Tegretol side effects in Asians include Stevens-Johnson syndrome and Toxic Epidermal Necrolysis, a severe skin sloughing disorder associated with the HLA-B*1502 allele mutation.