One of the central questions at the core of the Drug Allergy Clinic at Vanderbilt University Medical Center is this: What do you do when the drug you have reacted to in the past is the very drug that could save your life in the future?
The clinic, celebrating its 10th year, has seen groundbreaking discoveries in personalized care and diagnosis for allergy, especially delayed drug allergy, and has advanced discoveries in the optimal process to test patients for drug allergies, leading to the implementation of programs to tackle allergies at an institutional scale and resulting in significant changes in clinical practice in the field.
In addition to safely identifying and disproving low-risk allergies to various classes of antibiotics, those leading VUMC’s drug allergy clinic — Elizabeth Phillips, MD, Cosby Stone Jr., MD, MPH, and others — have been sought out by patients across the country as a center of excellence for patients with rare drug allergies that can be fatal.
Phillips, the John A. Oates Professor of Clinical Research and professor of Medicine, Dermatology, Pharmacology and Pathology, Microbiology and Immunology, is an expert in life-threatening delayed drug reactions such as DRESS (drug rash with eosinophilia and systemic symptoms), SJS (Stevens-Johnson Syndrome and TEN (toxic epidermal necrolysis).
Stone’s expertise is in anaphylaxis due to medications, a life-threatening reaction that affects multiple body systems.
“We’re studying why you can put something in your mouth or in your body and within 15 minutes to an hour, you’re suddenly in shock. You’re breaking out in hives; you’re swelling; and you end up in the emergency room being injected with epinephrine,” said Stone, assistant professor of Medicine in the Division of Allergy, Pulmonary and Critical Care Medicine.
The clinic, located within the Vanderbilt Asthma, Sinus and Allergy Program, has treated thousands of patients over the past decade, having established, developed and enhanced protocols for managing complex drug allergies that have changed practice guidelines.
Of 2,920 patients, 1,495 have been delabeled for penicillin, 907 for sulfonamide antibiotics and 847 for cephalosporins. A successful pediatric arm of the clinic, led by Allison Norton, MD, associate professor of Clinical Pediatrics, is also flourishing.
More than 100 fellows, residents and students have rotated through the clinic, including more than 35 allergy and immunology fellows who are trained in the clinic as part of their fellowship training program, many of whom have gone on to start their own programs, leading the way in practice-changing research and providing much needed services across the United States and other countries. Stone was one of those fellows.
“The clinic has pioneered many delabeling and other testing services and paved the way for many other centers in the U.S. and internationally to follow suit,” Phillips said. “It is still unique in the United States and even internationally in the collective expertise it offers to provide patient-centered approaches to drug allergy. We have been so fortunate to have a team of dedicated nurses and a responsive pharmacy service that have been absolutely critical to this cause — from delabeling multiple antibiotic allergies in one clinic appointment to assessing patients with high-risk and life-threatening reactions that threaten future health and medication/vaccine options to providing safe and personalized and precision medicine approaches.”
Penicillin remains the most frequently reported drug allergy, Stone said. Common reactions evaluated include hives, rash and itching, but severe reactions include anaphylaxis. Their research has shown that penicillin allergies are overreported and undertested, resulting in antibiotic treatments that are often less effective and more expensive for those who have been labeled allergic.
“The assumption for more than 80 years, since the introduction of penicillin, has been that if something happened when you took penicillin — a mild rash or you felt a little sick to your stomach — the next time is going to be the big one (reaction),” Stone said.
“At the time these concerns were warranted, as early penicillins administered were injectable drugs with less stringent manufacturing processes that more commonly led patients to be truly sensitized to penicillin. Over decades, however, with the advent of oral penicillins such as amoxicillin, patients are rarely sensitized to penicillins and very rarely develop severe reactions such as anaphylaxis.
“Most patients, even those that truly had an allergic reaction several decades ago, will lose the tendency to react at a rate of about 10% per year. The history the patient gives us is extremely valuable in telling us what risk category they are in and helps guide what type of testing we can use to safely disprove, but sometimes affirm, their allergy,” Stone said.
What Stone and his group have learned has enabled them to test patients at scale, first in the ICU setting in the hospital, at student health and in the clinic. “All of our studies where we have been implementing those programs in the hospital setting derived from that ability to separate those who have low-risk symptoms from those who might have a real allergy,” he said.
“If you look across the entire population of the U.S., about 15% of all patients report they have a penicillin allergy and 99.5% have never had that allergy tested. And that’s just one allergy,” Stone said. “Until more recently there was nobody systematically evaluating these patients to see whether they do or do not have allergies when we do test them.”
The drug allergy clinic is also investigating what happens in someone who has a true drug allergy. “Why did it happen to that individual? What’s different about their genetics and their risk factors?” Stone said.
About the same time the drug allergy clinic opened, in March 2014, the first patient was enrolled in a prospective biospecimen study for severe cutaneous adverse reactions ― DRESS and SJS/TEN. The patient happened to be the index case for the new genetic discovery Phillips’ group published between HLA-A*32:01 and vancomycin DRESS. SJS/TEN, which has an average mortality of 15-20%, and DRESS, which has a mortality of up to 10%, occur when the immune system overreacts to certain medications with symptoms taking a few days to six weeks to manifest after a person begins the problematic medication.
Symptoms of SJS/TEN include severe blistering skin disease and sloughing, with eye involvement with risk for blindness. Symptoms of DRESS include fever, rash, enlarged lymph nodes and organ failure. The treatment involves ceasing the suspected culprit medication immediately, and often steroids or other immunomodulatory drugs are required to stop the symptoms from progressing.
Stone and others in the drug allergy clinic are also helping colleagues in oncology manage patients who are allergic to their chemotherapy. Another patient population at VUMC that has benefited from drug allergy testing are patients who are undergoing transplant.
“If you’re ever going to benefit from having access to the right antibiotics, it’s when your immune system is compromised,” Stone said. “We’ve always prioritized transplant patients for our evaluations because we know within six months, they’re very likely going to benefit from the drugs we’ve freed them up to use.”
Stone said being able to help patients know what drugs they can and can’t take is rewarding.
“We all just want to know if a drug is safe for a patient to take or not and do this in a way that is a shared decision with the patient,” he said. “We’re all marching in the same direction, trying to find the safest and best options for patients. It’s a win-win situation not only for patients but for their providers, the hospital and the community at large.”
