Knee Pain Leads to Shocking Diagnosis: Medical Mystery Solved

— Siobhan Deshauer, MD, reviews a mystery diagnosis


Internal medicine and rheumatology specialist Siobhan Deshauer, MD, solves the case of Ravi, a 47-year-old man presenting to the emergency department with knee pain.

Following is a partial transcript of the video (note that errors are possible):

Deshauer: Today I'm going to tell you about Ravi. He is a 47-year-old man who lived in Toronto, who immigrated from India 16 years ago. Like many people his age, his knees started acting up a few years ago. He chalked it up to an old basketball injury and long hours sitting at his desk at work, but as you'll soon find out, Ravi wasn't your typical 47-year-old man and little did he know that his knee pain was actually a sign of something much more sinister.

Like so many other people, Ravi's knee pain flared up from time to time. When he felt the pain starting to come on, again, he did what he always did: rest, ice, and Advil. He didn't think much of it and expected it to improve over the next week or so like it always did.

But this time was different, the pain just kept getting worse. His knee was so swollen and painful that he couldn't even walk or straighten his leg. Nothing was touching the pain and eventually he couldn't even sleep. He really didn't want to go to the emergency department. He heard that the wait times were up to 18 hours, but he just couldn't hold off any longer, so he went to the hospital.

Of course, knee pain doesn't usually get prioritized in the emergency department, especially if it's not broken and you don't have a fever, so Ravi waited and waited until he finally saw a doctor about 10 hours later. On examination, the emergency doctor noted significant swelling of his right knee and severe pain with any movement.

This is really concerning for a septic joint, which is as bad as it sounds. Basically, bacteria start growing inside the lubricating fluid of your joint. Since we don't have many immune cells inside our joint to kill off bacteria, an infection can get out of hand really quickly. The emergency doctor ordered some blood work and an x-ray to get a closer look and this is where things get interesting.

Check this out. You don't have to be a radiologist to see that something is very wrong with Ravi's knee, so they did a CT scan to take an even closer look. It almost looks like someone or something took a bite right out of Ravi's bone. This is called an erosion and this one's particularly dramatic.

In the meantime, his physician reviewed his blood work. It was essentially normal, except for one test called the CRP, which indicates high levels of inflammation in the body. Now, we need to figure out what's destroying Ravi's knee and causing all this inflammation, and is it curable.

What we really need to get to the bottom of this is a sample of the fluid from Ravi's knee. This is actually a pretty common procedure called an arthrocentesis and I do it all the time as a rheumatologist, but some people definitely get a little squeamish. If you don't like needles, you may want to close your eyes for this next part. Basically, I sterilize and freeze the skin. Then I take a large needle and insert it deep into the knee joint.

In the lab, they ran the fluid through a cell counter, which showed high levels of white blood cells. Then they used a special microscope to look for crystals and it was crystal-clear. Finally, they used a Gram stain to look for bacteria and a special stain to look for tuberculosis. They found nothing, nada, not a single bacteria in sight, frustrating news for Ravi who was still in excruciating pain and just wanted to know the cause.

But the search for menacing bacteria doesn't end there. We still have to wait for the culture, which is when the lab tries to grow a bacterial colony out of the fluid sample, which usually takes a few days to come back. In the meantime, Ravi was admitted to hospital on IV antibiotics just to be safe.

Fast-forward a few days, the cultures still haven't grown any bacteria. Ravi is still on antibiotics and his knee is just as swollen and painful as ever. These are the moments you've just got to step back and think a little bit more broadly, so let's go back to the drawing board.

What's aggressively eating away at Ravi's knee and causing those huge erosions? It's definitely not the typical bacteria we see in a joint infection, but there are still some categories of bacteria and pathogens that don't get picked up on routine cultures and don't get killed by our strongest antibiotics, so we can't cross infection off just yet.

Could it be Ravi's immune system that's attacking the knee and eating away at the bone? Possibly, but it seems less likely. Blood work for specific antibodies came back negative, and after years of pain I would have expected other symptoms to develop in most autoimmune diseases. Crystals are also less likely, which brings us to cancer.

Ravi's doctors decided to scan his whole body for any tumors and it's a good thing they did, but not for the reason you might suspect. When the radiologist was scrolling through the images, no tumors or masses were seen, but something unexpected caught his attention. There were scars at the top of Ravi's lungs, finally another clue. But are they connected? What do his lungs have to do with his knee?

Ravi's doctor consulted the infectious disease specialist. She reviewed Ravi's case closely and three important clues stood out to her: 1) His knee pain had been going on for years, although this was by far the worst flare. 2) Ravi immigrated from India, which means as a child he was exposed to different infections that aren't common here in Canada. 3) Finally, he has scarring at the top of his lungs.

The infectious disease specialist called up the lab and asked them to run one more test on the fluid from Ravi's knee, a special test called PCR, which detects DNA from one particular bacteria that's extremely difficult to diagnose. When the test came back positive, Ravi was diagnosed with tuberculosis.

You might be thinking, "But the stain and the culture were both negative, how is this possible?" Well, as you'll see, TB is a super-sneaky bacteria. The stain is positive less than 40% of the time and the culture can take up to 8 weeks to grow, so we often turn to PCR to get a quick reliable answer while we're waiting for cultures. Okay. We have a diagnosis, but how did TB get in his knee? Isn't it normally a lung infection? If he caught the infection decades ago in India, why is he getting sick from it now?

Well, this is where things get really fascinating. Tuberculosis is a bacterial infection that has plagued humanity for millennia. We've even gone back and diagnosed Egyptian mummies with this disease. It ripped through Europe in the 17th to 19th centuries causing 25% of deaths. Think about that -- one in four deaths were caused by TB. We lost so many brilliant minds: Emily Brontë, Kafka, Thoreau, and Chopin, one of my favorite composers. Although they didn't know what caused it at the time, we now know that TB is a highly contagious airborne infection that's spread by coughing.

Most people develop respiratory symptoms -- cough, fever, and weight loss -- but it can also spread throughout the body. Even when the bacteria was discovered in 1882, it still took another 60 years to develop an effective treatment. In the meantime, people were sent to sanatoriums for rest and fresh air, which was considered the gold-standard treatment at that time.

Of course, fresh air wasn't the cure, but it was a really important public health intervention to isolate the affected people and prevent the spread, the same concept that was used in the COVID-19 pandemic when people were told to stay home. Fortunately, today we do have good treatments for TB, but it still remains one of the most difficult bacteria to identify and kill, but more on that later.

Let's get back to Ravi. How did tuberculosis end up in his knee? To explain that, we need to go back about 30 years when Ravi was growing up in India. As a teenager, he was exposed to a sick relative who had TB. The bacteria spread through the air and entered Ravi's lungs. Like 95% of people exposed, his immune system was able to contain the infection, so he had no symptoms. But don't be fooled. TB wasn't killed, it was just lying dormant like an undercover operative.

Here is what happened. When TB entered Ravi's body, it was quickly detected by his macrophages. Think of them like the immune system's security guards, always patrolling and looking for intruders. The macrophages acted according to protocol, engulfing TB and attempting to kill the bacteria. But TB came prepared with mycolic acid-armored plating. Not only was it able to resist these attacks, but it was able to live and replicate inside the macrophage, all according to its devious plan.

The macrophage sent out a distress signal and a whole army of immune cells came to the rescue. Ravi's immune cells literally squished together to form a tight spherical ball to wall off the infection and protect the rest of the body. This ball of inflammatory cells is called a granuloma. Think of it like a maximum-security prison to hold the intruder. Once TB is contained, it's not contagious anymore and we call this condition latent tuberculosis.

Believe it or not, 1.8 billion people worldwide are infected with latent tuberculosis. Many people live their whole lives with latent TB locked safely away in its granuloma prison, but for up to 10% of people, TB is able to break free when their immune system weakens and then it can wreak havoc on the body.

That's exactly what happened to Ravi 5 years ago. We don't know exactly what caused Ravi's immune system to weaken, but whatever it is, TB was able to escape from his prison, infiltrate into his blood vessels, and travel all the way down to his right knee, where it latched on and festered, slowly eating away at his bone until it looked like this.

Siobhan Deshauer, MD, is an internal medicine and rheumatology specialist in Toronto. Before medicine, she was a violinist, which is why is called Violin MD.