Overlooked Possibilities

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.

A Doctor Puts It Together

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.