An autopsy revealed the cause was DRESS — drug reaction with eosinophilia and systemic symptoms. It’s a rare but deadly condition triggered by medications often used to treat acne, seizures and gout.
Subtle at first and then terrifyingly intense, the syndrome isn’t well known. That makes it particularly dangerous.
“If you know what it is, you can diagnose and treat it,” says Izzy’s mother, Tasha Tolliver. “But it’s so uncommon that many physicians are confused.”
Ever since Izzy’s death nine years ago, Tolliver has been on a mission to warn other parents and doctors about DRESS, which affects as many as 1 in 1,000 people exposed to several commonly prescribed antibiotics and anti-seizure medications, including vancomycin, minocycline, lamotrigine, phenytoin and carbamazepine, as well as allopurinol, used to treat gout. DRESS is fatal in up to 1 in 10 cases.
Tolliver is haunted by two things: Her daughter’s death began with treatment for acne, something relatively benign. She also believes that clinicians’ misunderstanding of DRESS resulted in an avoidable delay in her daughter’s treatment.
“Losing my child continues to be a living hell that never gets easier,” she says.
Missed diagnoses
Experts agree that DRESS can fly under the radar — until it’s too late.
“There have definitely been cases where the diagnosis was missed,” says Steven Chen, who as director of inpatient dermatology consultation at Massachusetts General Hospital says his team sees patients referred to them with DRESS once every couple of weeks. He recalls one patient who said she had been hospitalized elsewhere for a “virus” after taking medication for acne. “She was one of the lucky ones,” Chen says. “She stopped the medication, and it went away on its own.”
“Most doctors should have learned about DRESS in medical school, but it can easily be overlooked if you’re not thinking about it frequently, especially since it’s relatively rare,” Chen adds. “It can get lost in the mix with all the other facts and information you are supposed to master.”
DRESS is one of several severe cutaneous adverse reactions (SCARs), the most well-known of which is Stevens-Johnson syndrome (SJS). But SJS primarily affects the skin, while DRESS involves internal organs, making it harder to quickly identify.
At Vanderbilt Medical Center, Elizabeth Phillips, the director of the Center for Drug Safety and Immunology, estimates that more than 7,000 people in the United States are suffering from DRESS at any time, and that up to 10 percent of those who experience the syndrome die within six months.
While most DRESS cases are mild, some survivors later develop autoimmune conditions including thyroid disease, lupus or diabetes. There is limited research about these risks, however.
“We desperately need long-term follow-up studies in the United States,” Phillips says. “Unfortunately, clinical trials are hard to do with DRESS because patients are so spread out. Patients need to be adequately followed to look for these complications,” she adds. “When a patient is diagnosed with an autoimmune disease after DRESS, the provider may not make the association between the DRESS and the autoimmune disease.”
Older people with preexisting medical problems are the most vulnerable, Phillips says, while women also seem to be slightly more prone to the syndrome than men, for reasons that are unclear. “One explanation may be because the severity of DRESS can depend on the dose,” she says, “and drugs are often prescribed in a one-size-fits-all mode that leads to over-dosing in some women.”
Minority group members appear to be more vulnerable to bad outcomes from DRESS, Phillips says, again for unclear reasons, although lack of access to high-quality medical care and specialists’ support might play a part.
“We do know that at least 20 percent of patients who have experienced DRESS do not have the culprit drug documented as an allergy on their record, and that minority groups may be at higher risk not to have DRESS documented as an allergy,” Phillips says. “This is a drug safety concern — particularly in that patients move from system to system in the U.S.”
Phillips is looking into hereditary factors that might make some people, including members of minority groups, more vulnerable to allergic reactions to medications. She hopes doctors may soon be able to offer genetic tests to screen patients for potential reactions to medications before they take the first pill.
Building awareness
In 2019, Tolliver co-founded the DRESS Syndrome Foundation, which she runs out of her home, with Nancy Szakacsy, whose daughter also died of DRESS-related heart failure.
Hannah Szakacsy, 17, had helped create an anti-bullying program and aspired to be a nurse practitioner. Like Izzy McKinney, Hannah also took an antibiotic to treat acne — in her case, minocycline.
Nancy Szakacsy, a licensed marriage and family therapist in Woodland Hills, Calif., describes Hannah’s subsequent 102-day ordeal in critical care, which included two open-heart surgeries, fasciotomies — cutting into the fascia, or connective tissue — in her legs, and the loss of her colon and part of her pancreas before her death, in a 2014 book called: “Hannah Was Here: DRESS, an Alarm That Must Be Heard.” Hannah wasn’t diagnosed with DRESS until after she died. Initially, doctors suspected she had mononucleosis before treating her for a drug reaction, according to her mother.
“If you know what it is, you can diagnose and treat it. But it’s so uncommon that many physicians are confused.”
— Tasha Tolliver, mother of Izzy McKinney, who died of DRESS at age 16
Tolliver and Szakacsy have assembled an archive of 640 patients, registered a National DRESS Syndrome Day (July 16, Hannah’s birthday), established a network of medical experts, created a video of interviews with survivors, helped fund and organize the first global DRESS Conference, and lobbied for more instruction about DRESS in medical schools. They regularly counsel people through their website, fielding one to three emails or calls a day, according to Tolliver.
“They’re like an international lifeline to so many patients, and they’re so spot on in what they do,” says Phillips, the foundation’s pro bono scientific adviser.
Hard lessons
DRESS was reportedly first described in the 1950s, when it was caused by anti-tuberculosis medications and referred to as anticonvulsant hypersensitivity syndrome. Its name changed a few more times over the years until DRESS was coined in 1996. Today, it’s also known as drug-induced hypersensitivity syndrome.
DRESS is a delayed reaction, experts warn, with symptoms appearing as much as two weeks after the first dose of medication.
Over his 12-year medical career, dermatologist Kyle Cheng, an attending physician at UCLA Health, says he has seen two patients die of the syndrome because they arrived in his care with their livers, lungs and hearts already failing.
“Patients shouldn’t be scared of taking these common medications, but if they develop rash or fever, they should stop the medication promptly,” he says.
They should also immediately seek care from their primary care physician, Phillips says. They may have a mild case, which can be treated with topical or oral steroids, or need more aggressive treatment.
“Communication between doctors is definitely important, so ideally one doctor, the primary care physician, is coordinating things,” she says.
Tolliver says she believes gaps in knowledge about the symptoms of DRESS led to differing opinions about her daughter’s treatment at VCU Health in Richmond, delaying critical treatment.
During her daughter’s first of two emergency room consultations, a dermatologist raised the possibility of DRESS, noting it in her records, Tolliver says. But a doctor later handling the case ruled out DRESS because Izzy didn’t appear to have eosinophilia — abnormally high levels of a type of white blood cell that is a common marker of DRESS, according to Tolliver. She said eosinophilia was detected only after Izzy’s death. Doctors treated Izzy for a Type-3 drug reaction, which is less severe than DRESS, Tolliver said.
A VCU Health spokesman declined to comment on the case, citing a confidentiality agreement related to a legal settlement. In court documents related to the settlement, the medical group associated with VCU Health denied “any and all negligence” in Izzy McKinney’s death.
“This is a drug safety concern — particularly in that patients move from system to system in the U.S. and the nature of a severe life-threatening reaction to a medication is not appropriately documented.”
— Elizabeth Phillips, the director of the Center for Drug Safety and Immunology at Vanderbilt University Medical Center
Late last year, the parents of a teenage girl who died of heart failure connected with DRESS after taking the anti-seizure drug lamotrigine sued Seattle Children’s Hospital for negligence and malpractice. Their lawsuit says hospital staff delayed treatment and downplayed the risks faced by their daughter, who was of South Asian descent, because of racism.
In legal filings, the defendants countered that the girl’s condition was “appropriately managed.”
“She was cared for and closely followed by multiple physicians,” their lawyers wrote. In an email, the family’s attorney, Martin McLean, said the case is set for trial in February 2025.
Steroids, careful follow-up
Treating DRESS may require steroid treatments for as long as a year, Tolliver says. In addition, experts warn that the heart should be closely monitored in all DRESS patients.
Heart issues “may go under the radar or only manifest upon cutting back steroids,” Phillips wrote in an email. “The only way to monitor this is to make sure to do careful follow-up of patients and be proactive about doing the electrocardiogram, echo [ultrasound of the heart] and measuring cardiac enzymes.”
In 2020, warnings about DRESS first appeared on labels for trimethoprim-sulfamethoxazole, according to an FDA spokesperson. Izzy McKinney had been prescribed the drug five years earlier. As of 2024, the American Academy of Dermatology (AAD) no longer recommends the drug for acne.
The AAD’s 2024 guidelines “make an effort to more strongly recommend against its use given the risks of acute respiratory failure and severe drug reactions,” says John S. Barbieri, a dermatologist at Brigham and Women’s Hospital who co-chaired the AAD’s acne guidelines working group.
The drug “may be associated with severe adverse reactions,” the AAD says, recommending further study.
AAD guidelines still recommend minocycline, the drug Hannah Szakacsy took, with advice that physicians should balance the benefits and risks.
“Acne is a very stigmatizing disease,” and treating it remains important, Barbieri says.
But, he adds, he feels minocycline is used too frequently, both because of a lack of convincing evidence of its effectiveness compared with other treatments and the risks of side effects including DRESS.
“These reactions are rare, but when they happen, they can be devastating,” Barbieri says. “That’s why in my practice I almost never use minocycline for acne.”
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