A deadly reaction to antibiotics often used to treat acne, gout and seizures is flying under the radar because it’s so rare, but experts, activists and broken-hearted families are urging more awareness of the syndrome.
Izzy McKinney was a healthy American teenager who wrote poetry and also had acne. She tried topical medications and then antibiotics. Two weeks after starting a doctor-prescribed antibiotic – trimethoprim-sulfamethoxazole – she developed a mild fever.
Less than three months later, one month after her 16th birthday, her heart failed, and she died, reports The Washington Post.
An autopsy revealed the cause was DRESS – drug reaction with eosinophilia and systemic symptoms. It’s a rare but deadly condition triggered by the medications. 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 her daughter’s death nine years ago, Tolliver has been on a mission to warn other parents and doctors about DRESS, which affects as many as one 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 one 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.
Missed diagnoses
Experts agree that DRESS can fly under the radar, until it’s too late. Early symptoms can include a fever of up to 40 degrees, fatigue, enlarged lymph nodes and a rash that spreads quickly and typically affects the upper trunk and face, according to the DRESS Syndrome Foundation.
“There have definitely been cases where the diagnosis was missed,” said Steven Chen, who as director of in-patient dermatology consultation at Massachusetts General Hospital said his team saw patients referred to them with DRESS once every couple of weeks.
DRESS affects as many as one in 1 000 people exposed to several commonly prescribed medications. Of those, up to one in 10 may die, according to the American Academy of Allergy, Asthma and Immunology.
Elizabeth Phillips, the director of the Centre for Drug Safety and Immunology at Vanderbilt University, said the seven drugs most frequently associated with DRESS are: antibiotics trimethoprim-sulfamethoxazole, vancomycin and minocycline; anti-seizure medications lamotrigine, phenytoin and carbamazepine; and allopurinol, used to treat gout.
Symptoms may include fever, rash, fatigue, facial and lymph-node swelling, an elevated white blood count and inflammation of major organs.
Eosinophilia – abnormally high levels of eosinophils, a type of white blood cells – is a common marker of DRESS. “But it may not appear right away, and steroids could mask it,” Phillips said.
“Physicians should be suspicious when any patient presents with a new rash for a drug that has been on the market less than five years.”
DRESS symptoms may not appear until two to eight weeks after the first dose of medication, according to a JAMA Dermatology patient page, which warns that patients should have regular clinic checkups and blood tests for five years after their diagnosis.
“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 added. “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 Centre, Phillips estimates that more than 7 000 people in the US are suffering from DRESS at any time, and that up to 10% 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 said. “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. When someone 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 pre-existing medical problems are the most vulnerable, Phillips added, 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 said, “and drugs are often prescribed in a one-size-fits-all mode that leads to over-dosing in some women.”
Minority groups appear to be more vulnerable to bad outcomes from DRESS, 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% 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 said. “This is a drug safety concern – particularly in that patients move from system to system in the US.”
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), like Izzy McKinney, also took an antibiotic to treat acne – in her case, minocycline.
Nancy Szakacsy 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.
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, said 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 said.
They should also immediately seek care from their primary care physician, Phillips saids. 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 co-ordinating things,” she said.
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 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 said. 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,” said Phillips. “The only way to monitor this is to do careful follow-up of patients and be proactive about doing the electrocardiogram, echogram 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”, said John 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 said, 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 stigmatising disease, and treating it remains important,” said Barbieri.
But 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. That’s why in my practice I almost never use minocycline for acne.”
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