Her lungs mysteriously shut down. How could this happen?

The 21-year-old gasped as she read the headline: “A 16-year-old girl who walks and eats tacos while on life support.” She looked at an article about a girl who had a mysterious illness that destroyed her lungs, and now she needed a machine to breathe for her. I need to do something, she told herself as she finished the article. She believed she knew she was killing this young girl because the story could have been her own six years earlier.

Then she was a high school student in the starting lineup of the women’s volleyball team. Just a few days into the new school year, she had a fever of 103 degrees and a sore throat. Her doctor in tiny Thief River Falls, Minnesota, suggested she had some sort of viral infection and predicted she would feel better after a few days of rest. He was wrong. The fever had gone, but was replaced by the worst fatigue the girl had ever known. Just getting out of bed, she was out of breath. Her mother took her to the nearest emergency room, 25 miles away.

When the nurse checked the young woman’s vital signs, she looked alarmed. The patient’s oxygen saturation, which would normally exceed 90 percent, was dangerously low at 60 seconds. The nurse put on an oxygen mask over her nose and mouth and reached for the attending physician. A chest x-ray showed a gray cloud infiltrating her lungs. Within minutes, she was in an ambulance bound for Sanford Medical Center in Fargo, North Dakota, the nearest hospital with a pediatric intensive care unit.

In Fargo, she was started on several broad-spectrum antibiotics. Doctors there didn’t know what germ was causing this pneumonia, but until they knew, they figured these antibiotics should protect her. But she got worse, and after a few days she had to be put on a ventilator.

When even that wasn’t enough, Sanford’s doctors contacted the Mayo Clinic in Rochester, Minnesota. Eight days after she entered the emergency room, the patient’s lungs were barely working. The next step was an artificial heart and lung machine known as ECMO, short for extracorporeal membrane oxygenation. This refrigerator-sized device acts like a lung, removing carbon dioxide from the blood and replacing it with oxygen, and then like a heart, returning oxygen-rich blood back to the body. The Mayo Clinic ECMO team flew to Fargo with their machine, connected the young woman to the device, and flew her back to the Mayo Clinic hospital. This machine breathed for her for the next 116 days.

Like the girl in the article, she too was walking while connected to a massive machine. She also ate while on the machine, though not tacos. The first thing that escaped her lips was the communion wafer when she finally felt well enough to walk at least part of the way to the hospital chapel, surrounded by a troop of doctors, nurses, and technicians. They never found out why her lungs failed. She spent months waiting in line for a transplant, waiting for new hearts and lungs to replace ones her doctors said would never recover. But they did. Finally, after seven months in the hospital, she was able to return home.

For several years after that, she came to Mayo every six months for a checkup. During these visits, she always stopped in the pediatric intensive care unit to see the nurses, who became like a second family to her during the months she was on the verge of death. During one visit, two years after her hospital stay, several nurses told her about a child whose illness was remarkably similar to her own.

Hours later, she and her parents met with the child’s parents, who told the story of their 12-year-old daughter, whose lungs simply stopped working after what looked like a viral illness. The families compared the records to see if there was any similarity between the lives and exposures of the two children. They lived in different environments – one rural, one urban – in different parts of the state. Nothing seemed to fit until, finally, the child’s parents revealed that their daughter had taken an antibiotic, trimethoprim-sulfamethoxazole (TMP-CMX), known by the brand name Bactrim, a few weeks before the hospital admission. The young woman gasped. She took this antibiotic (in her case for acne) – up until the day she went to the emergency room.

Since then, another family has contacted her and told her a familiar story: A healthy, active teenager fell seriously ill, his lungs were so damaged that he needed life support. She asked these parents if their son was taking TMP-SMX when he got sick. Yes, followed by a surprised answer. There were three cases in total. Maybe she found a real connection.

And now this young woman is on the news. Her name was Zei Uvadia. An article titled Dr. Jenna Miller as Pediatrician in the Intensive Care Unit of Children’s Mercy Hospital in Kansas City, Missouri who cared for Uwadia. The young woman found the doctor’s email address and immediately sent her a note. “I started taking Bactrim for acne about 3-4 weeks before [my] acute pulmonary insufficiency,” she wrote. “This happened to at least 3 children aged 12 to 20. [old]. … The similarities between our cases are striking.” She asked if Uvadia also took TMP-SMX.

Miller was amazed. Indeed, the girl was taking TMP-SMX when she got sick. Maybe there is a link? Miller turned to a friend, a doctor. Jennifer Goldman is a pediatrician trained in infectious diseases and clinical pharmacology. She studied adverse reactions to this drug for many years. TMP-SMX is effective, safe, and inexpensive, making it the sixth most commonly prescribed antibiotic in the country. It may be a coincidence that these four people, a small fraction of the millions taking this medicine on any given day, fell ill. However, doctors agree that they should investigate. The two pediatricians collected the medical records of the patient who sent the email and other cases she found. All were healthy young adults who developed severe lung injury after a brief flu-like illness, often accompanied by fever, sore throat or cough. And everyone was taking TMP-SMX.

What convinced the doctors that there was a connection was a biopsy of the affected lungs. Each showed the same unusual pattern of targeted destruction: the only cells in the lungs that were affected were those that took in carbon dioxide and supplied oxygen—the cells that do the most important work of breathing. In two, including the patient who first noted the link between her illness and the drug, these vital cells eventually grew back, allowing them to breathe on their own again. Others, whose lung tissue did not recover, required a lung transplant. Of these first cases, two died: a 12-year-old child whom the young woman met in Mayo, and Uwadia, a news girl.

In the four years since Miller received the patient’s email, she and Goldman identified a total of 19 patients, most of them under 20, who had this reaction after being treated with TMP-SMX. Six died. It is still unclear how the antibiotic causes this rare but devastating destruction. Goldman thinks it’s probably some kind of allergic reaction. But they still cannot predict who is at risk and why.

As an ICU doctor, Miller tells me she uses this drug frequently. While these cases are rare, the destruction they cause is horrendous. “Most of these people,” she says, referring to 19 cases, “was not treated for a life-threatening illness, and yet they were given this conventional medicine — and it ended their life or changed it forever.”

This original patient shares Miller’s mixed feelings. Now 26, she is a nurse caring for patients who have just had a heart and lung transplant. She regularly gives her patients TMP-SMX. And they need it – to treat diseases that they have, and to prevent diseases that they can get sick with. And yet she knows that because of her reaction to this drug, her lungs will never be the same again. She is able to play a friendly game of volleyball, but suffocates after climbing a couple of flights of stairs. However, she has a good life. And she’s proud to have made a contribution to science that she hopes will one day prevent this from happening to anyone else.

Lisa Sanders, MD, is the journal’s contributor. Her latest book is Diagnosis: Solving the Most Baffling Medical Mysteries. If you have a solved case to share, email her at Lisa.Sandersmdnyt@gmail.com.