Her mother had fallen and was too weak to get up, the kind voice on the phone explained. The call from the young woman’s aunt sent her hurrying to her mother’s home, just a town away in rural Alabama. The 68-year-old woman was back in bed by the time her daughter arrived.
Although the mother had been sick for several years, it was still shocking to see the pale, wasted shadow she had become. She’d been to the E.R. of the local hospital many times. She had even seen specialists in Tuscaloosa. But no one seemed to have a clue what was wrong with her.
As the E.M.T.s loaded her mother into the ambulance, the daughter asked if they could drive all the way to Birmingham. When she was pregnant with her triplets the year before, she’d traveled the 50 miles to see specialists at the University of Alabama Hospital in Birmingham. Maybe the doctors there could help her mom.
The doctors in the emergency room in Birmingham gave her mother some fluids to bring up her blood pressure, and she perked up a little. More important, they persuaded the older woman, and her daughter, to follow up at the university’s outpatient clinic.
Dr. Jori May, an internist in her second year of training, introduced herself to the thin, pale woman and her two daughters a month later. They offered May a thick stack of medical records they’d brought, and she put them aside to look at after. First, she needed to understand what had happened.
It started years earlier, the older woman told her. Almost every night, she would get these crazy fevers. First came bone-rattling, shaking chills; she couldn’t get warm even under a pile of quilts. Then suddenly she would be roasting hot, with sweat pouring off her. Her temperature would spike to 102 or 103. And her whole body would hurt, right down to her bones. She popped Tylenol constantly just to keep her fever down.
Then an hour after the fever hit, she would start to feel sick and throw up until she had nothing left in her. This happened almost every night.
During the day, she felt weak and tired, and her bones hurt. It made any movement painful. Her doctors called it fibromyalgia. She also had a rash. Hives, the doctors told her. It didn’t itch, but no one could figure out why she had it. And, her daughters added, she had no appetite. The very thought of food made her want to vomit, the older woman told May. She’d lost over 80 pounds this past year.
May could see how the patient’s clothes, eyes and even skin looked a couple of sizes too large. Otherwise her exam was uninformative. She didn’t have a fever, and she didn’t have a rash. May told the patient she would go through the stack of records and come up with a plan.
Reviewing them, May saw that the patient had a persistently elevated white-blood-cell count. Normal is under 10; the patient’s was at nearly 20 — and had been for a couple of years. CT scans showed enlarged lymph nodes throughout her body. These findings could be from a chronic infection. Or from a cancer. But her hometown doctors found neither.
May decided to think about illnesses that her first doctors hadn’t tested for. The woman needed to be checked for H.I.V.; patients over 55 are thought to make up a quarter of all cases — diagnosed and undiagnosed — and they are much less likely to be tested for it. Another possibility was syphilis, called the great imitator for its variable presentation. And given her persistent gastrointestinal problems, May would look for celiac disease. She also sent off a test to look for a type of blood cancer called multiple myeloma, which attacks the blood and bones and is seen in patients over 50.
May waited anxiously as the results came back. It wasn’t H.I.V. It wasn’t syphilis or celiac disease. The patient didn’t have multiple myeloma either, though that test, which measures levels of one part of the immune system known as antibodies, was abnormal; one antibody, known as IgM, was high. May referred the patient to an infectious-disease specialist, who found no infection. The oncologist found no cancer. And the dermatologist merely confirmed what May already knew — the patient had hives, and it wasn’t clear why. She presented her puzzling patient to every smart doctor she knew when she walked down the hospital hallway and at educational conferences. Yet after seven months of testing and referring and discussing, May was no closer to a diagnosis than she was on Day 1.
It was part of May’s weekly routine to check the patient’s chart for any new consultant notes or test results. One afternoon she was surprised to see an 11-page note from a pathology resident who, as far as she knew, was not involved in the case. It was a meticulous summary of all the patient’s symptoms as well as the many tests performed so far. He went on to suggest that she had a disease May had never heard of — Schnitzler syndrome. It was, as the resident described it, a rare and poorly understood immune disorder.
In Schnitzler syndrome, according to current thinking, the most primitive part of the immune system — a type of white blood cell known as the macrophage — goes wild and instructs the body to act as if it is infected. The body responds with fever and chills, a loss of appetite, flulike body aches, hives and high levels of one specific type of antibody: IgM. Exactly why and how this occurs is still unknown.
The disorder was first described in 1972 by the French dermatologist Liliane Schnitzler, who subsequently identified five patients with hives, episodes of prolonged fever, bone pain and enlarged lymph nodes. These symptoms, plus an elevated level of IgM, Schnitzler proposed, defined a new disease.
May didn’t know the resident who proposed the diagnosis, Dr. Forest Huls, but she’d heard of him. Huls, although still in training, had a reputation for finding cases that stumped others and figuring out the diagnosis. “When I see people suffering and I know that if I took the time and effort, I could figure it out,” he told me, “then I have to do something.” He looks for unexplained pathological findings — in this case, the high level of IgM.
Huls hadn’t heard of Schnitzler syndrome, either. He came upon it by using the database PubMed to look for a disease that matched the patient’s symptoms. He made a list of her symptoms and abnormalities. To get the full picture, he combed through her earlier electronic medical records, now archived in an old electronic warehouse, and found that her symptoms had started maybe a decade earlier. Then he looked for a disease that fit. It took hours before articles on this strange disorder began to appear. As he read, he suspected that she had it.
After reading Huls’s note, May looked up Schnitzler syndrome. Doctors’ descriptions of patients with the disorder matched her patient exactly.
It was an important diagnosis to make, in part because there is now a very effective treatment. When the woman’s insurance company refused to pay for the new and very expensive drug, May appealed to the manufacturer, which agreed, after several months, to provide it. Once she started taking it, the shaking chills and fever disappeared. So did the nausea and vomiting, the hives and bone pain.
Looking back at her life with this illness, the patient can barely recognize herself. Before her illness, she’d prided herself on her get-up-and-go and her disinclination to sit still. All those years stuck on the sofa and ultimately in bed, too sick, too weak and in too much pain to move, seemed like a chapter in someone else’s life.
As for Huls, he is finishing up his fellowship at the hospital this summer. Wherever he ends up, he is certain he will find new cases to challenge his curiosity, cases he hopes to solve.