An autopsy determined the cause was DRESS (drug reaction with eosinophilia and systemic symptoms), a rare but fatal condition caused by drugs commonly used to treat acne, seizures and gout.
Subtle at first, then terrifyingly violent, this syndrome is not well known, which makes it particularly dangerous.
“If we knew what it was, we could diagnose it and treat it,” said Izzy’s mother, Tasha Toliver, “but it’s so rare that it stumps a lot of doctors.”
Since Izzy’s death nine years ago, Toliver has been on a mission to warn other parents. Tell your doctor or health care provider about DRESS. DRESS affects 1 in 1,000 people exposed to commonly prescribed antibiotics and antiseizure drugs, including vancomycin, minocycline, lamotrigine, phenytoin, carbamazepine, and allopurinol, which is used to treat gout. DRESS is fatal in up to 1 in 10 cases.
Tolliver is troubled by two things: that her daughter’s death began with a relatively harmless treatment for acne, and that she believes the delays in her daughter’s treatment, due to clinicians’ misunderstanding of DRESS, were inevitable.
“Losing a child continues to be a living hell that never gets any easier,” she said.
Missed diagnosis
Experts agree that DRESS can go unnoticed until it’s too late.
“We certainly had cases where the diagnosis was missed,” says Steven Chen, director of inpatient dermatology at Massachusetts General Hospital, whose team sees DRESS-referred patients once every two weeks. He recalls one patient who was admitted to another hospital with a “virus” after taking acne medication. “She was one of the lucky ones,” Chen says. “She went off the medication and it cleared up on its own.”
“Most physicians will have learned about DRESS in medical school, but it can easily be overlooked if you don’t think about it often, especially since it’s relatively rare,” Chen adds. “It can get lost in the mix with all the other facts and information you need to master.”
DRESS is one of several serious cutaneous adverse reactions (SCARs), the best known of which is Stevens-Johnson syndrome (SJS), but it can be difficult to immediately identify because SJS primarily affects the skin, whereas DRESS affects internal organs.
Elizabeth Phillips, director of the Center for Drug Safety and Immunology at Vanderbilt Medical Center, estimates that more than 7,000 people in the U.S. suffer from DRESS at any one time, and up to 10 percent of those who experience the syndrome die within six months.
Most DRESS cases are mild, but some survivors later develop autoimmune diseases such as thyroid disease, lupus and diabetes, although research into these risks is limited.
“Long-term follow-up studies are desperately needed in the U.S.,” Phillips says. “Unfortunately, clinical trials for DRESS are difficult because patients are so widely dispersed. You need to follow patients long enough to find these complications,” she adds. “If patients are diagnosed with an autoimmune disease after DRESS, health care providers may not be aware of the connection between DRESS and the autoimmune disease.”
Phillips said older people with pre-existing conditions are the most vulnerable, and for unknown reasons, women also seem to be more susceptible to the syndrome than men. “One explanation is that the severity of DRESS may vary with dosage, and medications are often prescribed in a uniform way, which could lead to overdosing in some women,” Phillips said.
Phillips said members of minority groups appear to be more vulnerable to poor outcomes from DRESS, for reasons that are unclear but could be due in part to less access to quality medical care and specialist support.
“We know that at least 20 percent of patients who experience DRESS do not have the medication that caused the allergy documented in their records, and minority groups may be at higher risk of not having DRESS documented as an allergy,” Phillips says. “This is a medication safety concern, especially as patients move between systems in the U.S.”
Phillips is investigating genetic factors that may make some people, including members of minority groups, more susceptible to allergic reactions to medications. She hopes that doctors will soon be able to offer genetic tests to screen for potential responses to drugs before patients take their first dose.
Raising awareness
In 2019, Tolliver co-founded the DRESS Syndrome Foundation, which he runs from his home, with Nancy Sacassy, who also lost her daughter to DRESS-related heart failure.
Hannah Sacasy, 17, helped create an anti-bullying program and aspired to be a nurse. Like Izzy McKinney, Hannah was taking antibiotics to treat her acne, in her case minocycline.
In her 2014 book, “Hannah Was Here: DRESS, the Alarm Clock That Needed to Be Heard,” Nancy Zacassy, a licensed marriage and family therapist in Woodland Hills, California, described Hannah’s ordeal of 102 days in intensive care, which included two open-heart surgeries, a fasciotomy (cutting the fascia or connective tissue) in her legs, and the loss of part of her colon and pancreas before her death. Hannah wasn’t diagnosed with DRESS until after her death; her mother said doctors initially suspected mononucleosis before beginning treatment for a drug reaction.
“If we knew what it was, we could diagnose it and treat it. But it’s so rare that it stumps a lot of doctors.”
— Tasha Toliver, mother of Izzy McKinney, who died at age 16 in DRESS
Tolliver and Sacasy have collected an archive of 640 patients, registered a National DRESS Syndrome Day (July 16, Hannah’s birthday), built a network of medical professionals, produced video interviews with survivors, helped fund and organize the first World DRESS Conference, and lobbied for more instruction on DRESS in medical schools. Tolliver says they regularly counsel people through their website, fielding one to three emails and phone calls a day.
“They’re like an international lifeline for a lot of patients, and they’re doing the right thing,” said Phillips, who is an unpaid scientific adviser to the foundation.
Harsh lessons learned
DRESS was first described in the 1950s and was caused by antituberculous drugs and was called anticonvulsant hypersensitivity syndrome. Its name subsequently changed several times before the name DRESS was coined in 1996. It is now also known as drug-induced hypersensitivity syndrome.
Experts warn that DRESS is a delayed reaction, meaning symptoms may not appear until up to two weeks after the first dose.
Kyle Chen, an attending dermatologist at UCLA Health, said that in his 12 years as a doctor, two patients he saw after their livers, lungs and hearts were already failing have died from the syndrome.
“Patients need not be afraid of taking these common medicines, but if they develop a rash or fever, they should stop taking the medicine immediately,” he says.
Phillips says patients should see their doctor immediately: While some cases may be mild and treatable with topical or oral steroids, others may require more aggressive treatment.
“Communication between doctors is absolutely important, so ideally one doctor, who is the patient’s primary care physician, acts as the coordinator,” she says.
Toliver said she believes a gap in knowledge about DRESS symptoms led to disagreements about her daughter’s treatment at VCU Health in Richmond and caused important care to be delayed.
Tolliver said that during the first of her daughter’s two emergency room visits, a dermatologist raised the possibility of DRESS and noted it in the records. But a doctor who subsequently looked after the case ruled it out because Izzy did not have eosinophilia, an abnormally high level of a type of white blood cell that’s a common indicator of DRESS. She said the eosinophilia was only discovered after Izzy’s death. Doctors treated Izzy for a Type 3 drug reaction, which Tolliver said is less severe than DRESS.
A VCU Health spokesman declined to comment on the matter, citing confidentiality agreements related to the legal settlement. In court documents related to the settlement, the medical group with ties to VCU Health said: ‘Any negligence’ in Izzy McKinney’s death
“This is a drug safety concern, particularly in the United States where patients are moved from system to system and the nature of serious, life-threatening reactions to drugs is not properly documented.”
— Elizabeth Phillips, 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 after taking the anti-seizure drug lamotrigine, linked to DRESS, sued Seattle Children’s Hospital for negligence and medical malpractice, alleging that hospital staff racially delayed treatment and downplayed the risks their daughter, who is South Asian, faced.
The defendants countered in legal papers that the girl’s condition was “appropriately managed.”
“She was under the care of multiple physicians and under close monitoring,” the lawyers wrote. The family’s lawyer, Martin MacLean, said in an email that the case is scheduled for trial in February 2025.
Steroids, careful follow-up
Treating DRESS may require up to a year of steroid therapy, Tolliver says, and experts warn that all DRESS patients’ hearts need to be closely monitored.
Cardiac problems “may go unnoticed or only become apparent when the steroids are tapered,” Phillips said in an email. “The only way to monitor this is to follow up patients closely and aggressively with EKGs, echocardiograms, and other tests.” [ultrasound of the heart] Measure cardiac enzymes.”
According to an FDA spokesperson, a warning about DRESS first appeared on trimethoprim-sulfamethoxazole’s label in 2020. Izzy McKinney was prescribed the drug five years ago. As of 2024, the American Academy of Dermatology (AAD) no longer recommends the drug for treating acne.
The AAD’s 2024 guidelines “seek to more strongly discourage its use, given the risks of acute respiratory failure and severe drug reactions,” said John S. Barbieri, a dermatologist at Brigham and Women’s Hospital and co-chair of the AAD’s acne guidelines working group.
“The drug may be associated with serious side effects,” the AAD said, and recommended further study.
The AAD guidelines still recommend the drug Hannah Sacasy took, minocycline, but advise doctors to weigh the benefits and risks.
“Acne is a very discriminatory disease,” and treating it remains important, Barbieri said.
But, he added, he feels minocycline is used too often. No convincing evidence of efficacy Comparison with other treatments, including DRESS, and risk of side effects.
“These reactions are rare, but when they do occur, they can be devastating,” Barbieri says, “which is why I rarely use minocycline to treat acne.”
