For years, Stevens-Johnson syndrome (SJS) was viewed as one of the most unpredictable adverse drug reactions. A patient would begin taking a prescription drug, only to develop a rare but potentially life-threatening condition days or weeks later.
Researchers now know that some cases may not be entirely unpredictable. As scientists have learned more about why some patients develop Stevens-Johnson syndrome while others taking the same drug do not, genetics has emerged as one of the most promising areas of research.
Scientists have identified specific genetic variations that dramatically increase the risk of developing Stevens-Johnson syndrome or toxic epidermal necrolysis (TEN) after taking certain drugs. In some parts of the world, genetic screening before prescribing high-risk drugs has become routine. In the U.S., testing is recommended for patients with particular ancestries.
While genetic testing can’t prevent every case of SJS, growing research suggests it may help identify some patients before a dangerous drug is ever started.
Certain Genes Can Increase the Risk of Stevens-Johnson Syndrome
Stevens-Johnson syndrome remains rare, even among people taking drugs that have been linked to the condition. Researchers believe genetics may help explain why some patients develop SJS while most do not.
Most of the research has focused on genes within the human leukocyte antigen (HLA) system, which helps regulate the body's immune response. Certain HLA gene variants appear to make the immune system far more likely to trigger the abnormal immune response that leads to SJS and TEN.
Among the best-studied genetic markers are:
- HLA-B*15:02, strongly associated with carbamazepine-related SJS/TEN
- HLA-B*57:01, associated with hypersensitivity reactions to abacavir
- HLA-B*58:01, linked to severe reactions involving allopurinol
Researchers continue to identify additional genetic markers that may increase the risk of severe reactions involving other drugs.
Genetic Screening Has Already Reduced Some Cases of SJS
One of the clearest success stories involves carbamazepine, which is commonly prescribed to treat epilepsy, certain nerve disorders, and bipolar disorder.
Studies found that people carrying the HLA-B*15:02 genetic variant were far more likely to develop Stevens-Johnson syndrome after starting carbamazepine. Following those discoveries, several countries began recommending or requiring genetic screening before prescribing the drug to patients with ancestry in populations where the gene is more common.
Research has shown that screening programs can dramatically reduce, and in some studies nearly eliminate, carbamazepine-induced SJS among patients who test positive for HLA-B*15:02.
The U.S. Food and Drug Administration also recommends genetic testing before prescribing carbamazepine to patients with certain Asian ancestries because of this increased risk.
Why Isn't Genetic Testing Recommended for Everyone?
For most medications prescribed today, routine genetic screening isn't recommended because researchers haven't identified genetic markers that reliably predict Stevens-Johnson syndrome. Instead, current recommendations focus on certain high-risk drugs and patient populations where testing has been shown to reduce the risk of severe reactions.
Before prescribing those medications, healthcare providers may consider a patient's ancestry, current FDA recommendations, professional guidelines, and the availability of validated genetic testing. When a patient carries a known high-risk genetic variant, physicians may recommend an alternative treatment.
Even with these advances, genetic testing can't prevent every case. Many drugs associated with SJS don't have established screening recommendations, and many patients who develop the condition have no known genetic risk factor. Researchers believe immune responses, infections, dosage, and additional genetic factors that have not yet been identified may also influence who develops it.
As a result, healthcare providers continue to rely on careful prescribing practices, patient education, and early recognition of SJS symptoms alongside genetic screening when appropriate.
Could Failure to Order Genetic Testing Raise Legal Questions?
The availability of genetic screening has also raised new questions about medical standards of care. Whether a healthcare provider should have ordered genetic testing depends on numerous factors, including the medication involved, the patient's medical history, current prescribing guidelines, FDA recommendations, and the information reasonably available at the time treatment was provided.
Not every case of Stevens-Johnson syndrome involves medical negligence. Many cases occur even when healthcare providers follow accepted medical practices.
However, legal questions may arise if a healthcare provider failed to follow established prescribing recommendations, overlooked known risk factors, or prescribed a drug without recommended genetic screening when testing was indicated. Each case depends on its own medical facts and should be evaluated individually.
Genetic screening is unlikely to eliminate Stevens-Johnson syndrome, but it represents one of the most promising advances in preventing certain drug-induced cases. As researchers identify additional genetic risk factors and testing becomes more widely available, physicians may have more tools to identify patients at increased risk and select safer treatment options.
Even so, early recognition remains essential. Patients who develop flu-like symptoms, painful skin changes, blistering, or other signs of Stevens-Johnson syndrome after starting a new drug should seek immediate medical attention, as stopping the suspected drug promptly can significantly improve outcomes.
