Mystery Diagnosis: Martin

Who gets to make a diagnosis? Do I have the authority? Who would believe me?

Martin’s story starts on December 28th, on a snowboarding vacation. He was a slender 18 at the time, healthy, athletic, and an avid snowboarder. He spent the first week in Idaho, and called me near the end of his second week of vacation, in Colorado. He had a fever of 102, had a really sore throat, and had been sick for a couple of days. Today he was much worse, and had vomited twice so far.

It was winter, he was staying with a big group of people, and he had different kinds of symptoms. Strep throat can cause sore throat and fever, but doesn’t usually cause vomiting. I suspected the flu. I told him to make sure he had lots of sips of clear fluid, and call again if he got worse in any way. He was scheduled to return home tomorrow, on the weekend, and I told him that if he wasn’t better, I would see him right away.

In the office, he told his story. He started getting sick about 9 days before. His first symptoms were fatigue and nausea. He vomited once that day and had no appetite. From that evening a week and a half ago, he has had a fever up to 103. He’s had muscle aches and backache. Then the rash appeared. It’s not itchy, but it kind of hurt a little when touched and gave him a strange sensation he couldn’t describe. As I questioned him about every possible part of his body, he recalled that it hurt just a little to pee from the beginning of the illness. Over the previous 24 hours or so, it’s been hurting to pee more consistently, though he was sure there was nothing unusual leaking out of there. He’s vomited once or twice a day, but hasn’t had diarrhea. He wonders about a curious thing that he doesn’t think is related. He last weighed himself about a month ago; in my office that day, the scale showed that he had lost 10 pounds. I asked him about everything he did and everyone he was with. I asked him again about every part of him, from his scalp to his toes.

He looked thin and tired. It would be a thorough exam and I asked him to put on a gown but leave on his shorts. His eyes were a little pink and had a hint of crust on the eyelashes. He had denied any eye symptoms. His nose was stuffy and there were flakes of dried blood I could see when I looked in there. He hadn’t mentioned that, either. His abdominal exam was normal, but I noticed something that he said he hadn’t. On his undershorts, there was a little dark brown stain that looked like a dried drop of blood. His skin rash was very faint but I could just barely feel it. It covered his arms like a delicate pink lace all the way from shoulders to hands.

I sent him to the lab for blood and urine testing, and started him on antibiotics.

The next day I saw him again. He had called and said that over the last 24 hours he has gradually developed joint pain. By the way, he added, he cannot straighten his arms.

I ordered more tests, and x-rays of his elbows.

By January 4, both ankles were swollen. Not his feet, not his legs, just his ankles. Even short walks caused intense pain in both ankles. It didn’t hurt to pee any more. He had some diarrhea. The following day his right eye started to hurt whenever he looked upward. I pushed appointments aside and made phone calls. I was able to convince a busy local ophthalmologist to see him right away, and an orthopedic surgeon to examine his joints, and perhaps put a needle in one of them to draw off some fluid for analysis.

Every night, I was driving to the medical library at UCSF. One by one, I eliminated the likely diagnoses and most of the unlikely ones. There was one that kept fitting in: Reiter’s Syndrome. One of the older reference books I found had this mnemonic: ‘The patient can’t see, can’t pee, can’t bend a knee.’ I learned that it is most common in young white men, like Martin.

I saw him again on January 8th. He said that sometimes his right eye ‘doesn’t work’ and the lid is mostly closed. He has to open the lid using his hand. His fever was gone now, and he felt generally better. His elbows were better and his ankles no longer swollen but still painful. He noticed some bumps today under the skin of both his hands. The bumps I felt were like firm BBs under the skin on the tendons of his hands and the back of the wrist.

As a pediatrician, I hadn’t seen or heard of Reiter’s Syndrome since medical school, and it had not naturally come to mind. But then, suddenly, the bumps under the skin. Martin mentioned a sore throat at the very beginning of the story. When I did my residency in Utah, I learned that though it’s quite rare in the United States, the Rocky Mountain states have the highest incidence of rheumatic fever in the country. No one understands why. This brought on a new surge of investigation and laboratory testing. Among others, I tested him for evidence of a past Strep infection. That was positive.

Rheumatic fever is a complication of Strep Throat infections. To diagnose it, the patient needs to have 2 of these 5 criteria:

• arthritis of joints that seems to move from one joint to another
• nodules under the skin
• a long-lasting red rash that usually begins on the arms
• uncontrollable muscle movements
• inflammation of the heart

Martin had 3 of the 5, plus a couple of other things, considered minor criteria for this diagnosis:

• fever
• raised inflammation factors in his blood
• raised infection-fighting cells in his blood
• evidence of strep infection

He had started to get sick on a visit to the Rockies. Rheumatic fever can cause permanent damage to heart valves, so I arranged an urgent echocardiogram, which was normal.

So this is what he had, right? Well, that eye trouble didn’t fit in just right. And what about that pain when he peed? That’s not on the menu for rheumatic fever.

Reiter’s syndrome is diagnosed by meeting 3 criteria, called the ‘clinical triad’:

1. arthritis of multiple joints
2. urethritis
3. conjunctivitis

Martin had all of those.

Rheumatic Fever can be serious when it causes permanent damage to the heart. Knowing Martin’s heart was OK reassures me that if that’s what he had, it shouldn’t bother him any more.

Reiter’s Syndrome is a little more mysterious, and there are reports that some people who have had this have recurring arthritis.

If I really get to make the diagnosis, maybe he had both at the same time. He seems to be better now.

Fever -- 8 hot days

In my last post, Fever, I urged parents not to ask a doctor 'What could it be?' The list of possibilities is invariably a long one, and includes some extremely scary diseases that your doctor—like most doctors—has never seen in person. Good physicians always have in mind that if it walks like a duck, quacks like a duck...it's probably a duck. Any sound of hoofbeats is much more likely to be from horses than from a herd of zebras.

So when Matthew's mother called me to say that her 21-month-old has had a fever for about 4 days, I wasn't particularly worried, and told her that. I cared much more about how the child was doing—how sick was he?

Not very, she said. He had a fever pretty much continuously, up to the mid 104's (40°C). He felt lousy at those times, but his mother said that he perked up right away when the Tylenol kicked in. He was eating, keeping up with his fluids, acting like his usual self when the fever was kept down. I didn't need to see him—what was I going to do for him? If he was OK, then I was OK.

On day 5 of the fever, I called the family to check on him. Nothing much was new. Still had high fevers, but nothing in particular was hurting. I told the parents that as a rule-of-thumb, I usually order some basic tests if a child has about 5 days of fever without giving us any clue of what its from.

Most of the time, we don't find anything when we do these tests. And very often, the tests come back normal just as the rash is starting. One of the most interesting and sometimes frustrating common diseases of toddlerhood is Exanthema Subitum, also known as Sixth Disease, also known as Roseola Infantum. It's probably a deep truth about medicine that if you or somebody you know has a disease which has 3 different medical names, it's a good bet that medicine doesn't know much about it. In the 19th century and earlier, the cause of most diseases was completely unknown. So the classification system was based not on the cause of an illness, but on how the physician would witness it progressing. These days, we think of illness as either from a cause of some sort. Back then, there were 6 numbered rashes of childhood. First Disease, for example, is measles. Sixth Disease was a longstanding mystery until 1988 when the viral cause of it was discovered. Luckily, it seems to be the least dangerous of the numbered diseases. What makes it frustrating, and often results in lab tests that turn out to be unnecessary, is the high fever for day after day. Just like Matthew, the kids aren't very sick when we control their fever, which can last for days—usually 3 to 5 days, but I've seen it go a week. Then, mysteriously, the fever goes away and the child gets an awful-looking red rash over their whole body in a matter of hours. The rash doesn't hurt, doesn't itch, and goes away in 1-2 days without a trace and without treatment.

So I knew it was just a matter of patience. The parents, both scientists, were fine with that when I explained the plan. We'd take it day by day, and wait for the rash to appear.

On the morning of day 6, I called for a report. Nothing much was new with Matthew. But in the back of my mind was the fact that this was a boy, with a father is of Asian descent. The longer he went without getting the rash, the more I needed to question if I was right. While I was on the phone, I asked his parents to look at him and tell me if he had any rash of any kind, or if his tongue looked odd or if his eyes were red. I made them describe to me the skin on his hands and fingertips.

About 6pm on day 6, I called and was told that his eyes were a little pink. I drove to their house to look at him. Matthew was watching TV with his older brother, eating a banana. The boys didn't look up when I came in. His eyes were, in fact, a little pink. He wasn't rubbing them, and there wasn't any goopy stuff in the eyes. Everything else looked just as usual. I told the parents that I could wait no longer, and insisted that they take him for a blood test first thing in the morning.

On the evening of day 7, his fever still going, I got the lab results. There wasn't any particular evidence of infection in his blood, but his platelets were about 550, about twice the normal level. That was enough for me. I told them to take him right then, as soon as we got off the phone, to the emergency room at Children's Hospital Oakland. I called the ER and spoke to the doctor in charge so they'd be prepared for him. I told them he had Kawasaki Disease.

I came to the hospital later that night. The treatment was just getting started. We give an intravenous product of filtered, donated human blood called IVIG [Intravenous Immunoglobulin]. It's a liquid packed with all the antibodies and immune cells and chemicals from lots of people, with all the other blood components removed. It's like an immune-system sponge, which vacuums the system of illness-causing agents. We also give them aspirin, the ancient concoction originally from willow bark. It keeps platelets from sticking together (which they are supposed to do in order to help stop bleeding and form blood clots). By day 8, the next day, his platelet count was 750. If it kept going higher, he could be in danger from so many platelets clumping together, making the blood sludge in narrow vessels and potentially causing damage to major organs or a stroke. Matthew was about 26 pounds or so, and we were giving him 4 adult aspirin a day.

Kawasaki disease has yet another mysterious feature. It can cause coronary aneurysms in children. Usually only seen in older adults, these can be serious. They are weaknesses in the walls of the blood vessels that provide the heart muscle with blood. They form bulges in the vessel wall. If the weakened vessel breaks, part of the muscle will not continue working.

This disease is baffling, and reminds me that in past generations there were always those who wondered why they didn't know the cause of some illness even with their incredibly sophisticated 'modern' technology. The disease was only really identified (by Dr. Kawasaki in Japan) in the 1960s. With every technique of current molecular biology, no one has any idea of what causes this.

Because it has occasionally appeared to occur in clusters, it might be something infectious. But if it is, it's very hard to get. It's a rare disease. Maybe some people have a genetic predisposition to be susceptibility to it—it's more common in boys than girls and about 10 times more common in children of Japanese ancestry than in average American children. It's more common in children of other Asian descent than Caucasian children, but less common than in Japanese. Some people think that it's a lot more common than we know. Maybe those old people with aneurysms had unexplained fevers when they were kids, and nobody made anything of it at the time. But it weakened their vessel walls and 60 or 70 years later, they come to the attention of a cardiologist. Maybe adults are getting this disease too, but their symptoms are different. Maybe in adults they're just tired, feel run down, and keep forgetting where they put their keys....

Matthew never got all the symptoms of the disease. Since we don't know what causes it, there's no test for it. By the time I saw him on the evening of day 8, his eyes were very red. Within 12 hours of starting treatment, his fever was gone and he felt fine. Fortunately, the examination of his coronary arteries showed no aneurysms. Who knows how his disease might have progressed if treatment had been delayed by a few days? It's remotely possible he could develop heart-related problems later on, and he will be getting follow-up from the cardiologists. He seems to be fine for now, and he takes a chewable aspirin every day.

Don't ask your kid's doctor what it could be. Just try to find a doctor who knows that there are zebras out there, and who might recognize one at a distance.

Fever

Fever is one of the things our bodies can do to fight infection. It isn’t fully understood, but we know that many bacteria and viruses find the higher temperature a less appealing environment. There are many, many causes. Infection is the most common, but it can be caused by other problems as well.

In the second year of medical school, students are taught about all kinds of diseases. Some, of course, are serious, and some are usually not a big deal. Some diseases are common, and some are very rare. But nearly every student gets ‘medical student disease.‘ Day after day, they hear about exotic diseases that start…with fatigue. Then there’s the feeling that it’s difficult to concentrate. Maybe occasional headaches. They can’t help but put 2 and 2 together and end up with 73. That’s about the time when they are taught a favorite expression among doctors. ‘When you hear hoofbeats in the distance, it’s much more likely to be horses than zebras.‘ Which is simply a way of saying that when your kid gets a bloody nose, it's probably not Congo-Crimean Hemorrhagic Fever. For this reason, and as I’ve said before, it’s a mistake to ask a doctor ‘what could it be?’ That’s what medical textbooks are for, and I use them as references when needed. ‘What could it be?’ could only be thoroughly answered with zebras (all 4 kinds), camels (both kinds), and an occasional Java Rhino. Of course, your kid doesn’t have any of the vanishingly rare diseases that a single symptom—fever, for example—could possibly be.

I get a lot of calls about fever. For the most part, I can be very reassuring. It’s the body’s natural way of fighting off an infection. Fever from illness, it is generally thought, doesn’t get high enough to cause brain damage. Even a high fever (to the 105’s (41C)).

Hyperthermia can. That’s when our bodies are exposed to heat way beyond what our bodies can generate on their own. People stranded in the desert, for example--there’s a reason they call it Death Valley; or those tragic stories we read about every summer about a baby left in a car. Our bodies usually do a reasonable job in keeping us cool, by sweating. But if we get dehydrated and don't sweat enough, we could be in trouble if it were hot enough. Hyperthermia, though it does cause an abnormally high body temperature, isn't a fever.

Fever , then, doesn’t generally worry me. But what’s causing the fever? If I treat the sick child, it will be for the underlying illness, not the fever. Here's the scenario I pose to parents. If your child has a fever, but looks OK, is breathing fine and playing and active as usual, would you worry? Something is causing the fever, so I'll concede the child might be coming down with something, but that wouldn't worry me. Compare that to your child acting in a worrisome way—complaining of pain, for example, or sleeping all day and refusing to walk—but not having any fever. Is that reassuring? To me, that's much more worrisome.

So why do we treat fever at all?

There are purists out there who think that we shouldn’t treat it, and let the child’s body fight off the natural infections as millenia has designed us to. There are conspiracy theorists who believe that the companies marketing fever medicine want to support the mass delusion that fever must be treated.

For me, trying to see this from the child’s point of view, an empathic approach, is helpful. True enough, treating the fever does nothing to help get the child better faster or treat whatever illness they might have. But whenever we have a fever, we feel really bad. Sometimes fever can cause a headache, but it can certainly worsen a headache. But even without any specific symptoms, fever makes us feel sick. When we reduce the fever, we just feel better. And making children feel better is, as I look at it, an important part of my job.

I think parents with sick children often feel helpless as they watch their sick child. The fever is the only objective marker of the illness, whatever it is, and so by lowering the fever they feel like they are taking a pro-active approach. And they get positive feedback when their children perk up as their body temperatures go down.

If the child has a fever but is OK, I think it's all right to watch them and not treat the fever. If they feel awful, I would treat the fever. I don't think making the child suffer accomplishes much from a medical standpoint. But there's a few points that should be mentioned.

All kid's fever medicines are not the same. There are generally 2 choices of ingredient: acetaminophen (in Tylenol and a lot of store brands), and ibuprofen (in Motrin and a few others). They both work in most people, but it does seem that one will work better than the other in some people. Acetaminophen is safe when the directions are followed. It shouldn't be used for more than a few days, however, because at doses much higher than we should be giving, it can be toxic. Besides, if your child is really having a fever for more than about 3 days, it's probably a good idea to try and figure out what the kid has. A doctor might be able to help with that.

About 1 in every 25 kids get febrile seizures. They don’t seem to have epilepsy, but when their temperature is high enough, they have a brief seizure. It’s almost always in toddlers. As you can imagine, this is really scary for the parents. Fortunately, it’s quite common (about 1 in 25 toddlers have one), and most of those who have one never have another. The seizures do not cause brain damage, usually only last less than a minute, and usually do not mean that the child will go on to have a seizure disorder.

Every now and then, I see a child with fever who has been covered in as many blankets as the parents can manage. This is not a difference in parenting philosophy—it's just wrong. When we have a fever, our bodies are too hot. Even if we feel cold or are even shivering. In order to relieve the symptoms of fever, we have to lower our temperature. So dress your child minimally, and get rid of the heavy quilt on the bed. One of the best techniques I have found is to put the child in a bath. Not a cold bath! That would annoy anybody, especially a sick child. So draw a regular-temperature bath for them. It will still be about 20 degrees below their elevated body temperature. After soaking for 15 minutes (with you there—don't leave them alone in the bath), the water will have absorbed some of their temperature, and they will feel much better. You can do this as often as needed, without concern of overdosing.

Fever that has been relentless for more than 3 days, say 4 or 5 days, is worthy of a doctor visit. I'm still not worried about the fever causing damage, but I am concerned about finding a cause.

Elvis Presley live: Fever


Fever does, in fact, usually go up at night.