The 28-year-old woman had just put her 6-week-old baby down for a nap when the now familiar sensations began. Cold descended on her body as if it were a frigid January in their small town of Bettendorf, Iowa, and not a golden April morning. Her teeth chattered and her arms and legs shook and jerked, shivering to heat this self-made winter. Minutes later the cold disappeared, replaced by an achy heaviness and heat. A thermometer confirmed what the new mother and her husband already knew. Her fever was back.
This had been a pattern, once or twice a day, for the past two weeks: bone-rattling cold quickly replaced by the heat of fevers that rose to 102 or 103 degrees and lasted until vanquished by acetaminophen. She already had been to the urgent-care center in Moline, Ill., just across the Mississippi River, where she was given a 10-day course of antibiotics. But that day she would take the last dose, and still the intermittent fevers raged on. Even when they subsided, as they always did, she still had some pain between her legs from the stitches she received when the baby was born. That pain disappeared a few days after she got home but suddenly reappeared with her fevers — a full month after her delivery.
That morning the worried young parents packed up their baby and headed to the OB-GYN clinic at the University of Iowa Health Care Medical Center in Iowa City where they had a previously scheduled follow-up visit.
Searching for an Infection
The midwife listened to their story and then gently examined the woman. It was clear that some of the stitches hadn’t held, and the torn skin, carefully sutured at the time of the birth, had reopened, oozing purulence in a couple of places. The whole area was exquisitely tender. She was admitted to the hospital and immediately started on two broad-spectrum intravenous antibiotics.
The next day, she was taken to an operating room and put to sleep so that the region could be examined more fully. Under the bright lights of the O.R., it was clear that the open areas of the suture line had been infected, but after the antibiotics, they appeared to be healing well. An examination of the cervix was unremarkable. Nor did her breasts show any signs of the inflammation that can complicate breastfeeding. It was all very reassuring to her doctors. And yet she continued to have these dramatic daily fevers as she remained in the hospital.
So where was the infection? Cultures from the surgical site were uninformative. Samples of her blood and urine grew no bacteria. A CT scan didn’t show any hidden areas of inflammation or clots that might have been seeded with germs. And the patient herself had no other complaints.
Dr. Daniel Livorsi reviewed the patient’s chart carefully before introducing himself. He was a specialist in infectious diseases, he explained, and he was there to help her team figure out where her fevers were coming from. Livorsi peppered her with questions looking for possible exposures. She had moved to the United States from India three years earlier. Too long ago, Livorsi thought, for her fevers to be caused by almost anything she might have brought with her. Her parents came to stay with her when the baby was born, but they were healthy. And she didn’t eat any of the foods they brought from home. Her exam was likewise unrevealing, like all the tests she’d had in the hospital.
Back in his office, he considered what he knew about the patient and where to go next. Her fevers came too late to be a complication of her delivery; she was fine for a month after her baby was born. Instead, this was something known in medicine as an F.U.O.: a fever of unknown origin. In infectious disease, these are the cases that require the doctor to put on his deerstalker cap to find a hidden culprit.
It could still be some kind of bacterial infection; there were organisms that didn’t grow well in laboratories. Livorsi ordered blood tests for tuberculosis and other unusual infections. He also had to check some of the hiding places favored by bacteria: an ultrasound to look for a bug growing in the heart, an M.R.I. to look for an abscess deep in her abdomen or pelvis. If these tests detected nothing, it probably wasn’t bacterial and they could stop the antibiotics. And if not a bacterium, maybe a virus. Epstein Barr, cytomegalovirus and their ilk could cause these kinds of persistent fevers. Livorsi ordered blood tests to look for an immune response to these and other viral possibilities.
Of course, infection was not the only cause of mysterious fevers. Autoimmune diseases could do this. So could certain cancers. The team had already reached out to rheumatology to look for immune disorders. He suggested they consult hematology to look for cancers in the blood.
Finally, if all else failed, they could perform a PET scan. This kind of imaging looks for cells that are more active than their neighbors. The test can’t tell you what’s causing the activity — whether an infection or a cancer — but it can tell you where. The tests and their results stretched out over days of disappointment. The ultrasound, the M.R.I. and the dozens of blood tests provided no clues.
An Ominous Lead
Finally, after a week of daily fevers and no answers, the PET scan was done. It didn’t supply the diagnosis, but it did provide an important finding: Bright colored nodules of hyperactive cells were scattered from neck to pelvis. These were the lymph nodes, apparently hard at work. The report from the radiologists suggested that this could be some kind of widespread inflammation, possibly caused by an infection or autoimmune disorder. Or it could be lymphoma, a cancer of the immune system.
When Livorsi came by for his visit that day, the patient was alone and scared by the results of the PET scan. The doctor settled on the windowsill next to the bed. He had spoken to the hematology service, he reassured the anxious mother. They were pretty sure this wasn’t cancer. But she was scheduled to get a biopsy the next day and that would show what was going on in these hyperactive lymph nodes.
The next day was Friday. A needle biopsy of one of the enlarged lymph nodes was done. The results wouldn’t be back until the following week. The husband worked hard to keep his wife distracted, but he could tell that she was afraid. He was too. When Livorsi came by to visit on Sunday, the doctor could feel their fear. “When will we know for certain if this is cancer?” the patient’s husband asked. The biopsy would provide the answer, he told them.
The results finally came back on Thursday. The pathology was clear: She had Kikuchi disease. This disorder is often mistaken for lymphoma or lupus and only a biopsy can prove it’s not cancer, and a negative test for autoimmune diseases, like the one she’d had, can prove it’s not lupus.
The team hurried to tell the patient. Kikuchi? “Is that some kind of cancer?” she asked. Not at all, they assured her. Kikuchi disease was thought to be an abnormal immune reaction, sometimes in response to a viral infection. But it was new enough and rare enough that it was still not well understood.
She’d had the classic symptoms: fevers, fatigue and lymph nodes swollen with remnants of destroyed immune cells. But the best news was that the disease usually went away without treatment within a few weeks. Her last fever had been four days earlier. After three weeks of daily fevers, it looked as if it were finally over for her.
She could go home, they told her, and if she spiked another temperature, she could come back. But she probably wouldn’t. She went home with her baby. She was worried — but the fevers never returned.
I spoke to the patient recently, and she feels great. She’s tired, of course. Her baby is only 4 months old, and even with the help of her husband and parents, caring for an infant is a hard job. But it is, she tells me in a weary, happy voice, a job she loves.
Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write to her at [email protected].
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