Antibiotics, anticonvulsants, and antivirals are commonly prescribed for several conditions and illnesses. Yet, many of these widely taken drugs may induce an uncommon but severe immune reaction — and the medical community is still learning why.
Severe cutaneous adverse drug reactions (SCARs) are immune-related conditions whose delayed and severe onset can cause hospitalization and even death. Although usually treatable, these conditions — which includes DRESS Syndrome — are widely misunderstood. We need more research into the mechanisms of these diseases to ensure that patients receive appropriate diagnoses and treatments. Luckily, several committed physicians and researchers are dedicated to decoding the genetic and immune processes of these severe drug reactions.
Today, we’re interviewing Dr. Elizabeth Phillips, scientific advisor of the DRESS Syndrome Foundation (DSF). She's also founder and director of Vanderbilt University Medical Center’s Center for Drug Safety and Immunology (CDSI). As a global expert on SCARs, Dr. Phillips is working to identify genetic factors associated with DRESS and SJS.
DRESS Syndrome Foundation (DSF): You are a world leader in SCARs research and founded VUMC’s Center for Drug Safety and Immunology. What has motivated you to pursue this mission?
Dr. Elizabeth Phillips: My mission started when I was training in infectious diseases and I saw frequent reactions to medications that no one understood how to manage. My passion to pursue infectious diseases started early when I saw the power of being able to recognize and treat something through to a cure. Many myths about drug reactions existed at this time. Caring for patients with HIV was particularly humbling because it required managing drug toxicities while also keeping patients medicated long enough to have some effect. Beyond that, patients with HIV were 100x more likely to have reactions to common medications, such as Bactrim, which was lifesaving in preventing pneumonia.
I was fortunate to find a center for excellence in drug safety in Toronto, where I had already trained in Infectious Diseases and Microbiology. I spent additional time doing a research fellowship in drug allergy while developing my own research niche in HIV drug safety and starting a clinic. At this time in Toronto, I took over the Clinical Pharmacology Training program and Division Head Position of Clinical Pharmacology. Here, I realized that physicians were not well trained to recognize severe drug reactions nor remove false allergy labels (like penicillin). This began what would unfold over time to be several layers of my career.
DSF: Why is it important to identify genetic associations with adverse drug reactions, such as Vancomycin and DRESS?
Dr. Elizabeth Phillips: Understanding genetic risk is a first step in personalizing therapy and making medications safer for patients. Only a small portion of those carrying genetic risk will develop a severe hypersensitivity reaction such as DRESS. However, knowing about genetic risk for DRESS Syndrome is a useful tool for healthcare providers, who may choose to avoid the medication or follow the patient carefully.
I was fortunate to be involved in implementing a routine prescription screening test to prevent hypersensitivity to the antiviral drug abacavir. Thanks to this test, health care providers who trained after 2008 have almost never seen a case of abacavir hypersensitivity! In other words, the widespread use of this genetic test transformed abacavir into a newer and safer medication that saved many lives.
DSF: Do you expect your research findings to eventually influence how clinicians prescribe drugs?
Dr. Elizabeth Phillips: The research is moving quickly, and I think the findings will lead to new insights and ways of preventing, diagnosing, and treating these terrible drug reactions. Recognizing when and how to use testing is important, and recognizing a reaction early before it can cause harm to the patient is also important. We are developing tools to understand how to reduce drug hypersensitivity reactions globally, as well as reduce the short- and long-term effects they produce.
DSF: What are some of the most significant barriers to your research?
Dr. Elizabeth Phillips: This is still a small and largely under-recognized field that does not have dedicated funding. Clinical education is so important, and in the United States, there is huge energy surrounding drug allergy that is influencing a new generation of clinicians. While this is important, we also need infrastructure and support to mentor physician scientists who will lead the way in transforming many aspects of science. I would like to see dedicated funding to address false antibiotic allergy labels and drive the science of severe drug hypersensitivity reactions such as DRESS Syndrome.
DSF: What does it mean for a patient who tests positive for having a genetic factor that can influence a SCAR reaction? How might they move forward?
Dr. Elizabeth Phillips: Right now, knowing the results of a genetic test is like a safety filter. While it’s unlikely that someone with a positive genetic test will develop a hypersensitivity reaction, recognizing this risk can bring them some peace of mind. Particularly, if other drugs exist that are equally effective, this personalized medicine approach is ideal and can help patients totally avoid toxicity. However, a negative genetic risk factor does not completely rule out the risk of a drug hypersensitivity reaction, even with the drug in question. For patients who have experienced a drug hypersensitivity reaction, learning about a genetic risk factor may reassure them about their risk for future reactions. This result can be a huge relief and weight off them by alleviating fears of taking future medications.
DSF: Genetic testing is rapidly evolving. What types of genetic/drug association testing do you see on the horizon, and how do you expect this to impact the incidence of SCARs?
Dr. Elizabeth Phillips: Hypersensitivity risk associated with specific drugs is like a mosaic puzzle. We are starting to get much more clarity, but we still have some missing pieces. And these missing pieces will define the strategy.
Genetic testing has come down in cost and feasibility, so we can do simple, very inexpensive genetic tests in less than 3 hours. For some drugs, there may not be just one genetic risk factor across a diverse and heavily admixed population in the US. Therefore, the future may mean each patient will have a panel of genes available to clinicians so they can understand the safest prescription approach. This is somewhat similar to how the medical community currently approaches cancer and is not that far away in the future. Aside from prevention, genetic testing will be useful in classifying risk , making diagnoses, and correlating drugs and their reactions.
DSF: Is there anything else you would like to share about your work or CDSI?
Dr. Elizabeth Phillips: It feels like it has been small baby steps, but I believe we are in line with and getting to our mission, which is extremely gratifying. Our mission is to grow international research in all aspects of drug safety to promote advancing the science and education of drug hypersensitivity reactions. We have had success in prevention and are getting closer to advancement in new frontiers, such as earlier diagnosis and identifying new drug targets. These advancements could transform both drug hypersensitivity and other aspects of medicine that depend on this research. Seeing such an explosion of new interest in this field gives me confidence that these problems will be solved soon, and we just need the persistence, grit, and funding to get there!
I am so grateful to Tasha Tolliver, Nancy Szakacsy, Deanna Lorianni, and others at the DSF for their energy, passion, drive — and all they do to raise awareness and contribute to drug hypersensitivity education. The intersection and interactions with the community is one of the most gratifying and rewarding elements of being a physician scientist in this field.
Call to Action: Researchers Need More Government Funding
A major takeaway Dr. Elizabeth Phillips wishes to share is increased recognition and funding for clinical care associated with severe drug reactions. To date, no dedicated government funding exists for SCARs research, unlike many other diseases. Without funding, the research community will be forever held back in their ability to make strides in understanding and eradicating SCARs like DRESS Syndrome. It’s our aim to continue sounding the alarm about the importance of government, institutional, and industry funding — and to help charge a path toward adequately backed research.