Diagnosis: Solving the Most Baffling Medical Mysteries

Book Preface

The lights in the doctor’s office were almost too bright for the fifty-year-old woman to bear, but she forced herself to open her eyes. A young doc-tor knocked, entered the exam room, and introduced herself. She seemed sym-pathetic and interested as her patient described her miserable week and the travel that preceded it.
She hadn’t felt well since she and her kids had gotten back to Chicago from their two-week trip to her parents’ home in Kenya. This had been her first visit in nearly a decade—since before her kids were born. And now that they were old enough, she had been eager to show them where she grew up. She had gotten them all the right vaccines, and she had made sure they took the medi-cine to prevent malaria every single day. She didn’t want the trip, or their mem-ories of this place she loved so much, to be spoiled by illness. It was a great trip. But coming home had been brutal. Her children recovered after a day or two of jet lag. She didn’t.
She gave it a week, but every day she felt worse. She was tired, as if she hadn’t slept for weeks. She was nauseous. She felt hot and sweaty, like she had a fever. And her body ached like she had the flu. She called her doctor’s of-fice, but her doctor was out of town. So she found another who, miraculously, was able to see her the following day. And now here she was.
The patient paused, then added, “I think I’ve felt like this before.” When she was seven years old, living in Kenya, she had a bout of malaria. She thought maybe that’s what she had now. It sure felt like it.
The doctor nodded—it was a reasonable theory. Malaria is endemic in re-gions like sub-Saharan Africa and the most common cause of fever in travelers returning from there. And since she’d had it before, she knew the achy, flu-like symptoms of the blood-loving parasite.

Still, the doctor told her, she’d need a little more information. Any other medical problems? Absolutely not. Before her trip, she’d been completely healthy. She took no medications. Didn’t smoke or drink. Worked in an office. She was divorced and lived with her two children. She’d taken the preventive meds every day, starting two weeks before their trip, as prescribed.
The doctor moved the patient to the exam table. She didn’t have a fever, but she’d taken acetaminophen earlier that day. She was a little sweaty, and her heart was racing, but otherwise her exam was unremarkable.
Malaria made sense to the doctor. There is a type of malaria in parts of Kenya that isn’t killed by the usual prophylactic medications. And if she had al-ready had the infection for more than a week, it was important to start treat-ment quickly, the doctor told her. She gave the patient a prescription for a three-day course of antiparasitic medications. The woman took the prescription gratefully. She looked forward to feeling better at last.
This is the usual story of diagnosis. A patient feels sick. She recognizes that there is something wrong, but she may wait a day or two before seeking help. Things often get better on their own. But when they don’t, she will often seek help from her doctor.
From there, it’s the doctor’s job to solve the puzzle. Listening to the pa-
tient’s story is key. In nearly 80 percent of cases,*1 that is where the most im-portant clues can be found. An examination may offer additional clues. Some-times a test reveals even more. And it’s up to the doctor to put it all together and make the diagnosis.
Before I went to medical school, all I knew about diagnosis was what I’d seen on TV. It was an almost instantaneous one-liner dropped at a dramatic moment—just after the patient’s opening story of symptoms and suffering and just before they’re whisked away for a life-saving treatment. I believed that di-agnosis was a puzzle that I, once I was a doctor, could easily solve.
During med school, I put in the hours to learn the building blocks of diagno-sis—chemistry and organic chemistry, physics, physiology, pathology, and pathophysiology. As I finished my schooling and started on the apprenticeship component of my training, I developed a series of what doctors call “illness scripts”—detailed inventories of symptoms and their variations, progressions, and resolutions, which create a picture of a particular disease. Once these sce-narios were committed to memory and mastered, they could be deployed as needed. Nausea, vomiting, and diarrhea that rapidly sweeps through a family is a viral gastroenteritis. The sudden onset of fever, body aches, and congestion during flu season means the flu. Or in this case, those same symptoms in a traveler returning from Kenya likely mean malaria. We see the symptoms. We recognize the pattern and immediately know the diagnosis.
Fortunately, that is what happens most of the time—up to 95 percent of the
time, according to one study.*2 It is a skill set that delivers—most of the time. But what about those other cases? The 5 percent where the doctor has no an-swer. Or worse, the wrong answer?

The sick woman thought she had malaria. So did her doctor. But after the three days of pills, she felt even worse. She was so weak she could hardly move. She vomited nonstop. She felt feverish. Sweaty. Her heart pounded furi-ously. She couldn’t eat for four days and couldn’t even get out of bed for two. Finally, she called the doctor, who promptly sent the woman to the emergency room.
In the ER, an examination showed the woman’s heart was racing and her blood pressure was high. Her white-blood-cell count was dangerously low, and her liver showed evidence of injury. It wasn’t clear what was wrong with her, so she was admitted to the hospital.
The doctors in the hospital gave the woman medicine to stop the vomiting. That helped. But after several days it still wasn’t clear what had made her so sick in the first place. It clearly wasn’t malaria. She’d had three blood smears examined in the lab. And although she wasn’t running a fever when the blood was drawn—that’s when the test for malaria works best—none of these smears showed any sign of the parasite that causes this potentially deadly illness.
Her doctors hypothesized that her symptoms were a reaction to the medica-tions she’d been prescribed for the malaria they now knew she didn’t have. That seemed possible, especially since she was feeling a little better. Once she could eat, she was discharged from the hospital.
But back at home, the patient started throwing up again. She toughed it out for a week but finally dragged herself back to that same community hospital. The doctors there were worried enough by her condition to transfer her to Rush University Medical Center, where many of them had been trained. They were certain that their colleagues at Rush would be able to solve the puzzle.
The doctors at Rush consulted an infectious disease specialist—what else could this woman have? She was in the hospital for a week. She saw so many doctors. She had so many tests. When the vomiting was under control and she could eat, she was sent home and told to follow up as an outpatient with the in-fectious disease doctor. But after a few days she was back at Rush, just as sick as she’d been the first time.
More doctors, more tests. Tests of her urine, her stools, her blood. CT scans, MRIs. Even a biopsy of her liver. The results weren’t all normal, but they also didn’t seem to add up to a clear diagnosis. She was given half a dozen an-tibiotic, antiviral, and antiparasitic medications. If the doctors couldn’t figure out what she had, they could at least try treating her for what she might have. But none of the medications helped. What could she have picked up in Kenya?The dozens of doctors she saw were all asking that same question.
This is, perhaps, the most uncomfortable place to be in medicine, the land of uncertainty. It is uncomfortable for the patient—because not only are they still suffering from the symptoms that led them to seek care, they still don’t know the cause. Will it get better on its own? It hasn’t so far. Isn’t there a test for this? And yet dozens of tests, sometimes more, have been unrevealing. Will it kill them? How can anyone give a prognosis without a diagnosis?

It’s also uncomfortable territory for the doctor. One of the reasons that it may take doctors several tries before they discover the right diagnosis is that uncommon diseases often look a lot like their more run-of-the-mill counterparts early on. The body has only a few basic ways to let us know something’s wrong—what we call symptoms. But the possible causes of those symptoms are many. It’s like the relationship between letters and words—only twenty-six let-ters, but millions upon millions of words. In medicine there are dozens of symp-toms. But according to the International Classification of Diseases, there are nearly ninety thousand diagnoses.
Of course, no single doctor knows all ninety thousand—though some doc-tors know a lot more than others. Once the possibility of an unusual diagnosis is raised, there are a few ways to supplement the knowledge a doctor lacks. There’s the old-fashioned but often effective method of simply asking a col-league. Or there’s the much newer method of consulting the peripheral brain—the Internet.
But even when we have all the data, a condition can still go undiagnosed. A disease recorded on a page or in a database often looks very different from the same disease living in a patient. The earliest studies of diagnosis, done in the 1970s, showed that the doctor most likely to make a difficult diagnosis was the one who had seen the disease before, firsthand. Personal experience can be more important than book knowledge.
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After several weeks in and out of the hospital, the patient found herself at home, too weak and too sick to care for her children. She called her closest friend and asked her to stay with her and her children while she tried to re-cover. “Of course,” the friend told her, and quickly packed a bag. Upon arriving at the woman’s apartment, the friend was horrified by the woman’s appear-ance. Her face was thin and gray. Her lips were pale. “You have to call your doc-tor,” the friend said as soon as she heard the woman’s story. “Dr. Brown will know what to do.”
Dr. Marie T. Brown had been the woman’s physician for more than twenty years. The woman called the office and made an appointment later that week. Dr. Brown was also shocked by the appearance of this patient she knew so well. Normally she’d see her once a year for a routine physical. They’d catch up on life and health and then say goodbye until the next year. She always looked healthy and robust. But not now.
When Dr. Brown entered the exam room, the patient was hunched over a basin, and the acrid scent of vomit filled the air. She had clearly lost a lot of weight, and her eyes and cheekbones were prominent on her much thinner face. Her left leg trembled and jerked uncontrollably. What in the world hap-pened to you? the doctor asked.