Risk of Fatal Drug Allergy Can Now Be Assessed Through Genetic Testing
Posted on Nov 26, 2013 by Ailee Slater (G+)
In the past 20 years, our understanding of the human genome has lead to many advances in medicine. Health care workers are now able to test a patient for genetic susceptibility to an inherited disease such as breast cancer or Huntington’s disease. In the future, gene therapy may even make it possible to avoid a disease altogether. At the moment, genetic advances are small yet significant. Most recently, a study conducted by researchers from China and Singapore discovered how genetic testing might be able to predict which patients will and won’t experience a drug allergy – an allergy so severe that it usually proves fatal.
The drug is called dapsone. Dapsone is an antibacterial medicine used to treat bacterial infections as well as to stop swelling in the brain or other body parts. In patients with HIV, dapsone is often prescribed to prevent or treat the lung infection pneumocystis pneumonia, as well as to prevent the brain infection known as toxoplasmosis. Patients with other autoimmune disorders such as lupus may also take dapsone to treat infections, and the drug is likewise prescribed to patients experiencing leprosy or a similar skin disease. Dapsone may even be used to treat the poisonous bite of a brown recluse spider.
Dapsone is highly effective, but side effects can be severe, and a small number of people taking the drug will experience a hypersensitive reaction: fever, anemia and a rash, and eventually, severe damage to internal organs, and death. Researchers estimate that Dapsone Hypersensitivity Syndrome (DHS) affects up to 3.6 percent of all patients treated with the drug, and DHS will be fatal to nearly 10 percent of those people affected. A patient with DHS may be unaware that they are experiencing abnormal side effects and fail to seek medical treatment; and making the drug sensitivity more dangerous still is the fact that symptoms might not manifest for up to six months after the patient has stopped taking the drug.
The recent study on DHS and genetics was funded by the National Natural Science Foundation of China and the Medical Leading Scholar of Shandong Province Project, along with the Agency for Science, Technology, and Research of Singapore, and others. Researchers looked at 872 patients who had taken dapsone as a treatment for leprosy. Of those patients, 39 had demonstrated evidence of dapsone hypersensitivity. After looking at the genotype of all participants, as well as evaluating an additional 31 people who had previously experienced DHS, researchers concluded that individuals who carry one copy of the genetic molecule HLA-B*13:01 are 34 times more likely to be afflicted by DHS than individuals who do not carry that molecule. People with two copies of the HLA-B*13:01 are around 100 times more likely to experience dapsone hypersensitivity.
This study may have big implications for the future of genetic testing, and how it can be used to prevent adverse drug reactions. Prior to this DHS study, doctors had no way of knowing if a patient might experience a hypersensitive reaction to dapsone. Starting now, genetic testing can be used to assessed a patient’s DHS risk factor; if the patient has two or even just one copy of the HLA-B*13:01 molecule, her physician might consider a different course of treatment. More research into other drug reactions and their potential basis in genetics could lead to great advancements in pharmaceutical safety.
Being able to genetically test for DHS susceptibility will mean medical efforts to prevent the syndrome, rather than searching for a treatment. Antibiotics are not able to stop DHS, and although glucocorticoid type drugs are usually recommended in DHS treatment, these medications can have a number of worrisome side effects: glaucoma, cataracts and osteoporosis, to name a few. With genetic testing, however, a patient can discover his DHS risk before ever taking dapsone, eliminating the need for DHS treatment (and harmful side effects of that treatment) altogether.
Another interesting finding of the China/Singapore DHS study was that different ethnicities showed different likelihoods of carrying the HLA-B*13:01 molecule. The allele was mostly absent from study participants of European or African descent, and much more common in people from Asia. Researchers reported that HLA-B*13:01 is found in 2 to 20 percent of people with a genetically Chinese origin; in 1.5 percent of those from Japan; in 1 to 12 percent of people from an Indian origin; and in 2 to 4 percent of those with Southeast Asian heritage.
Could other drug allergies be detected in the same way? It certainly seems likely. Genetic testing already allows many women to assess their breast cancer risk, and take preventative actions (a mastectomy, normally) to avoid this inherited disease. In the future, genetic research such as the recent study into DHS susceptibility may offer even more options for people looking to understand more about their genetic risks, and take actions to prevent an allergic reaction or even a disease before it occurs.