Fever Without a Cause

My boyfriend needs some more codeine for his headache, the caller said. Even over the phone, the edge in her voice told me something was terribly wrong.  Would you start at the beginning? I asked.  The woman took a deep breath and began. Two days ago my boyfriend came to your emergency room. He’d been having terrible headaches and fevers for five days before that. His temperature was 104 when the doctor saw him, so she thought he might have an infection in his head. . . .  Meningitis?  Yes. She did a spinal tap so she could get some fluid out of his spinal column to see if it was infected. So far all seemed in order. A man with a fever. A man with a headache. Meningitis might explain both symptoms, and it might kill him if it went untreated.  Then she told us that Timothy didn’t have meningitis. She said he had a bad virus and that his fevers and headaches would go away over the next few days.  And?  They haven’t. He’s getting worse. He’s sitting here shaking, his teeth chattering. He’s drenched in sweat and has a terrible headache. It’s been over a week now. Could you please call in a prescription for some codeine? The edge returned to her voice. But I was a bit skeptical of the scenario Timothy’s girlfriend had described; it would be somewhat unusual for a viral infection to make someone sick for so long. And not only was Timothy not getting better--it seemed he was getting worse.  Put him on the phone, I told the young woman. Timothy greeted me a few moments later, sounding tired.  Forget about the codeine, I said to him. We need to find out why you’re still having these fevers. He grunted in agreement. Come back to the emergency room right now.  Within an hour Timothy and his girlfriend arrived. He was 36 years old, ruggedly built, with chiseled features and chestnut brown hair. His pale face was partially covered with several days’ worth of beard, and his shirt was drenched in sweat. His temperature was 101.  I think my temperature’s broken for the time being, he said quietly. It comes twice each day--early in the morning and again in the evening. I take some aspirin and sweat it out. My teeth rattle like mad, and sometimes the whole bed seems to be shaking with me. He was describing what doctors call rigors--the severe, shaking chills that accompany high fevers.  I asked him to tell me his story again, then repeated it back to him to make sure I’d gotten all the details right. This was one of the things I loved about medicine: the search for details that, while they might seem completely mundane to a patient, when applied correctly might solve the riddle of his or her illness.  Timothy sat back in his chair, leaning his head against the wall. He told me that until a week earlier he had been in perfect health. He remembered the first moment he felt sick: he was walking to his car with his girlfriend after a meal at an Italian restaurant. A chill came over him and his teeth began to chatter. He went home, his head pounding, and stayed in bed for the next four days. His headaches came and went with his fevers. Then, two days ago, he had come to our emergency room.  At first I suspected endocarditis, an infection of the heart valves that can be caused by infection during dental work or by injecting drugs with dirty needles. One of its symptoms can be intermittent fevers. I asked whether Timothy had ever used intravenous drugs or had had any recent dental work. No, he answered gruffly. And he denied any risk factors for hiv infection. Thinking he might have contracted some animal-borne infection, I asked if he had any pets. But Timothy said he didn’t have any pets, and he assured me that he hadn’t been hiking in woods or fields where he might have been bitten by ticks. So tick-borne diseases, such as Lyme disease or Rocky Mountain spotted fever, seemed out of the question.  When I asked if he had traveled abroad recently, he said no. He mentioned that he had gone to Mexico six months earlier and to Thailand a year earlier, but he hadn’t become sick during either trip. It seemed unlikely that a parasitic infection or bacterial disease contracted abroad would manifest itself so dramatically 6 or 12 months later.  I then reviewed his dinner the night he got sick. Spaghetti and meatballs, salad, gelato; two glasses of red wine; a cup of coffee-- decaffeinated. His companions had eaten the same dishes and drunk the same wine; all were healthy. So food poisoning was unlikely.  When I asked about possible exposure to illnesses on the job, he told me he was a freelance writer. Little risk of febrile illness there.  I examined him thoroughly, listening long and hard to his lungs, heart, and abdomen. I pushed everywhere, pulled on his extremities, twisted his fingers, looking for some sign of the swelling and tenderness that can signify joint disease or an autoimmune disease such as lupus. I peered into his nose, mouth, and ears. All seemed in order.  Despite our growing reliance on expensive medical technology, common illnesses can usually be diagnosed simply by listening to a patient’s story, obtaining a medical history, and performing a physical exam. But in Timothy’s case, technology was all I had left. I began with the basic tests, sending Timothy to radiology for a chest X-ray and then to the laboratory for routine blood and urine tests for bacterial infection. His chest X-ray was normal--no sign of the haziness that fluid or inflammation in the lungs can produce. His urine was clean--free of bacteria and white blood cells--and his white blood count, which infection commonly elevates, was also normal.  I continued seeing patients while Timothy waited patiently for the lab test results. His fever had subsided and he had begun to look and feel better. Though a few more lab tests were still being performed on his blood, I decided to let him go home, where he would be more comfortable. But I made him promise to return the next morning, and I assured him that we would discover the cause of his fevers. While an unusual virus might still be at the root of his troubles, I was convinced that something else was going on. But I didn’t know what.  Timothy thanked me for my efforts and headed out the door. I sat down at the computer and began reviewing his lab results. They were normal- -I hadn’t missed anything. Even technology was failing me.  A moment later, the last of his blood tests appeared on the computer screen. These tests screened for enzyme activity in the liver, and they were slightly elevated. The elevation was so minimal, in fact, that I wouldn’t have paid attention to it in another patient. I stared at the screen for several minutes. That slight rise might indicate inflammation in the liver. These slightly abnormal blood tests were the only clue I had to the cause of Timothy’s fevers.  I leaped out of my chair.  I’ll be right back, I said to one of the other er physicians. I rushed out of the ambulance bay doors and jogged toward the parking lot. At the far end of the huge lot I saw a head of chestnut brown hair slowly making its way down an aisle. I caught up with Timothy just as he and his girlfriend were getting in her car.  You need to come back, I said. His girlfriend rolled her eyes. Twice we had failed to diagnose Timothy’s illness, and here I was chasing them through a parking lot just after telling them to go home.  I tried to explain about the liver tests. They looked skeptical. It’s all we have, I pleaded. I want you to stick around a little longer so that we can have the radiologists perform an abdominal ultrasound. They’ll use sound waves to get a look at your liver and gallbladder, to see if there’s something there.  Like what? Timothy asked, tilting his head to one side.  I’m not sure. I’m groping, but it’s all we have to go on. I looked into the eyes of a young man who had barely been sick a day in his life. Like most people suddenly struck ill, he just wanted an answer, a cure, and to get on with his life.  Look, I’d really like to get home and get some rest, he said, eyeing his girlfriend’s car. About 14 hours of sleep would feel good right now. I’ll come back in the morning.  It’s important you come back now, I repeated. I felt foolish for having let him go before all his lab tests were back. Now I stood in the parking lot begging him to return for more tests that still might not provide an answer. He stared at me, then glanced over at his girlfriend. He shrugged, pivoted, and began walking slowly back toward the emergency room.  One hour after I’d sent Timothy up for his abdominal ultrasound, the radiologist called. I hope you put this guy’s admission papers in, he said, because he’s a keeper if ever I’ve seen one.  I swallowed hard.  What did you find?  There’s an abscess the size of a volleyball in the right lobe of his liver, one of the biggest I’ve ever seen, he replied calmly.  Timothy returned to the emergency room a few minutes later. I put him on a gurney, and a nurse started an iv line.  What’s that thing in my liver from, Doctor? Timothy asked.  Apparently it’s filled with fluid, probably pus. It could be a bacterial infection that spread from your colon into your liver or spread from somewhere else in your body. I thought about his travels--a trip to Mexico six months earlier and Thailand a year earlier. Or it could be from an infection that you picked up in another country.  That evening, Timothy spiked another high fever and looked extremely ill. Because the test results identifying the infecting organism would not be back for several days, the doctors caring for Timothy assumed he had a bacterial liver abscess and ordered that a catheter be put into his liver to allow it to drain. They also started him on an antimicrobial drug that would clear any parasitic organisms. With Timothy as ill as he was, compulsivity might pay off.  Two days later I stopped in to see Timothy. He looked much better and tossed a friendly smile my way. He said his catheter was going to be pulled out that day.  You were persistent, he observed, and I thank you for that.  I only wish we had a better idea of what caused this thing, I told him.  Amoebas is what they tell me, he said, chuckling. They think I might have picked them up in Mexico six months ago. Until now, I didn’t have any idea I was infected.  When Timothy’s blood tests finally came back, they were positive for exposure to Entamoeba histolytica, an amoebic parasite that feeds on red blood cells in the human gut. The parasite passes from host to host in capsules shed in the feces. People tend to become infected when they ingest these capsules, either through fecal contamination of water or food or by direct fecal-oral contact. After the capsule is eroded in the intestine, the parasite invades the intestinal lining, usually causing diarrhea, abdominal pain, and bloating. This form of infection, called amebiasis, is common in Mexico and other developing countries. Something as simple as a garden salad might have been the source of Timothy’s infection.  But people suffering amoebic infections can sometimes be symptomless for months. And in rare cases, the amoebas can spread from the colon to the liver, as they had in Timothy. When this happens, the body mounts an immune response to try to wall off the organism and prevent it from spreading to other tissues. The result is a pus-filled abscess.  In most cases of amoebic abscess, patients develop symptoms within three or four months. But Timothy was his own patient, not a statistic, and it had taken more than six months for the abscess to make him ill. Even more surprising was that the huge abscess hadn’t provoked any tenderness over his liver. Presumably it had grown so slowly that it hadn’t caused any noticeable pain.  As is so often the case, the answer to a puzzling ailment had been in the patient’s medical history. I realized now how vital Timothy’s travels outside the country were to understanding his mysterious fevers. Fortunately, Timothy was recovering rapidly and would be discharged in a few days. When I stopped by for a last visit, he bore no resemblance to the weakened, haggard man I had met in my er room. I looked at him, restored to health by a simple antimicrobial treatment, and smiled.