No DRESS rehearsal for life-or-death decision
It was just a rash.
Sandra Rosales of Stratford, Connecticut, noticed it on her leg one day at the end of May 2015. Just some little red spots that hadn’t been there the day before.
“I thought I had the flu,” she said. “I was like, ‘Oh, who knows, probably something I ate.’”
By the next day the rash had spread to her other leg. She went to a walk-in clinic to have it examined.
Rosales, then 37 years old, learned she had a condition called Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), a severe, but often treatable, drug allergy. It affects 1-5 patients per 10,000 exposed to certain medications and kills 5%-10% of them. Rosales had recently started taking minocycline, a commonly prescribed acne medication. It had triggered the reaction.
“Sandra’s case kept evolving,” said Brett King, M.D., associate professor of dermatology at Yale and one of Rosales’ physicians. “Her immune cells, called eosinophils, began attacking her heart. Later they attacked her spinal cord. It was an extreme case.”
DRESS triggers an immune system reaction that targets and infiltrates vital organs such as the heart, kidneys, and liver. In this case, DRESS rampaged through Rosales’ body over the next several months, severely damaging her heart, leaving her paraplegic, and nearly killing her. What saved her life was a bold move by King, who has a history of successfully treating a variety of skin diseases with a medicine best known for treating rheumatoid arthritis. The outcome suggests that for the first time an effective treatment may be possible for other patients suffering extreme DRESS.
The standard, but not always effective, treatment for DRESS involves large doses of prednisone, a synthetic steroid often used as an anti-inflammatory medication. King had initially prescribed this for Rosales.
But prednisone didn’t help. In fact, her condition worsened.
By the end of 2015 she had congestive heart failure, and at one point needed a balloon pump to help her heart function properly.
Rosales, a dental hygienist, was unable to work; her husband, Elkin Rodriguez, was holding down two jobs to make ends meet. The stress and worry continued to build.
“Psychologically speaking, I wasn’t there,” Rosales said. “It was too much for me.”
During hospitalizations, large doses of prednisone would temporarily quiet the DRESS immune reaction and Rosales would be able to go home, only to relapse a short while later. She developed a lung lesion; her heart had to be shocked back into proper rhythm twice. She was in the hospital more than she was at home.
“The medical community is at a loss for what to do when DRESS is this severe,” King said.
But he saw a way forward, far off the normal path.
In recent years, he had pioneered the use of JAK inhibitors — drugs that ease joint pain and swelling — for treating a variety of intractable skin diseases, including alopecia areata, eczema, and vitiligo. As part of his treatment plan for Rosales, King had prescribed tofacitinib, a medicine for rheumatoid arthritis and other autoimmune conditions.
“I had previously shown that tofacitinib suppressed bad-acting eosinophils in patients with a possibly similar disease called hypereosinophilic syndrome,” he said.
Then Rosales had a relapse coinciding with a period in which she was not taking tofacitinib.
“We connected the dots,” King said. “When she came off this medicine, bad things happened.”
After yet another period in which Rosales was not taking tofacitinib, she again started to become ill. King believed the solution was to restart the tofacitinib, ultimately at a higher dose, rather than treat Rosales again with large doses of prednisone. If he was wrong, the consequences for Rosales could be fatal — without prednisone the disease could attack her heart again. Rosales and her husband agreed to the approach, as did her Yale cardiologist, Dr. Tariq Ahmad.
“Within hours (of treating Rosales only with tofacitinib), the fever went away and she felt better,” King said. Within a week, the eosinophils in her system normalized.
“She has been well ever since, taking nothing but tofacitinib,” King said. She will likely need to take the medicine for the rest of her life.
There are no ongoing, large-scale studies to test the overall effectiveness of tofacitinib or similar medicines to treat DRESS — but that may change. King is in the early stages of planning such a study. In the meantime, Rosales’ case provides useful anecdotal evidence for other patients and physicians dealing with DRESS, King said.
“It was a really hard decision to make,” he said, reflecting with Rosales during an interview about her case. “There are no rules, because there aren’t enough cases in the medical literature, not enough guidance to create rules. You’re on your own.”
Rosales interrupted. “But I did great!” she said. “I’m here!”
King is an investigator and consultant for Pfizer, the manufacturer of tofacitinib, and participates in its speakers bureau.