Join internal medicine and rheumatology specialist Siobhan Deshauer, MD, in unraveling a medical mystery. Can you figure out the diagnosis before it's revealed?
Following is a partial transcript (note that errors are possible):
Deshauer: Hey, guys. I'm Siobhan, an internal medicine and rheumatology specialist. Today I'm sharing with you a fascinating story of a middle-aged woman who came to the hospital with unusual symptoms.
Her medical team was at a loss, unable to pinpoint the underlying cause -- that is, until they ask the right questions and order one simple blood test to confirm the diagnosis. I want you to learn how to think like a doctor, so let's dive right into the video and together we'll unravel this medical mystery.
Meet Jennifer. She is a healthy, active 54-year-old woman, who is currently training for a 5 km run. Over the past few months she has been having increasing fatigue and some knee pain, but she figured it was from all the extra running she has been doing. The pain then spread from her knees down to her shins into her calves, so she decided to run a bit less and stretch a bit more, but the pain kept getting worse.
Then she started developing bruising at the back of her legs, but she didn't remember bumping into anything. Even more concerning, she started developing these tiny red dots on her legs. But they weren't itchy and they weren't painful, so she didn't want to bother her doctor about it. She was hoping the rash would go away on its own, but it just kept getting worse, and over the course of 2 weeks her legs became so painful that she was actually having difficulty walking. At this point, her family convinced her that she had to go to the hospital.
When she arrived at the emergency department, her heart rate was a bit fast at 103, but her blood pressure was fine and she didn't have a fever. She has never really liked hospitals, so she figured she was just a bit anxious, which was raising her heart rate.
After waiting for hours in the emergency department, she finally saw the doctor who ordered some blood work and closely examined her legs. He noticed the rash and found some mild swelling in her legs. But what really stood out is that whenever he would touch her calves, she would be wincing in pain, and the level of pain seemed way out of proportion compared to the rash and the degree of swelling.
As a doctor, you're trained to think about the most deadly conditions first -- the things that you absolutely cannot miss. When it comes to leg swelling and severe pain, you have to think about a blood clot, because if it's left untreated the blood clot can travel up into the lungs and that can be fatal.
Jennifer was sent for an ultrasound of her legs, which ended up being normal -- no signs of a blood clot. Then she went for x-rays. Could there be something with the bones, maybe a rapidly progressing infection or a fracture, or maybe a tumor? Nope, nothing wrong with the bones or the joints.
But the x-ray did show subcutaneous edema, which just means that there is fluid buildup, swelling, in the tissue of her legs. Usually when I see leg swelling, I'm thinking about problems with three main organ systems: the heart, the liver, and the kidneys.
But Jennifer's case doesn't fit those patterns and the degree of pain far outweighs the amount of swelling, which really concerns me. Plus, the rest of her physical exam and blood work doesn't go with heart failure or liver or kidney disease. It's really unusual. To better understand what's causing her pain and swelling, she went for an MRI of both her legs.
This is what the cross-section of her thighs looks like on MRI. See the white arrows pointing to that bright white area? That's abnormal fluid buildup in the skin and tissue. The black arrows are pointed to the same thing happening in the deep fascia.
Based on where the fluid is distributed in her leg and the amount of pain that she is in, it's most likely that this is all caused by an inflammatory process. But where is that inflammation coming from? Well, you certainly don't want to miss a hidden cancer, so the team ordered a CT scan of her chest, abdomen, and pelvis, which didn't show any signs of cancer. And the MRI of her legs didn't show a tumor, so we can pretty safely cross that one out. She wasn't in an accident and she doesn't have diabetes, which leaves infection and inflammation in the muscles as our top causes.
Next, she went for an EMG [electromyography], which is the test that measures the electrical activity produced by a muscle. These reports get super technical. But usually when there is muscle inflammation, there is something abnormal and it will help us figure out the cause. But shockingly this came back normal too. Jennifer is in pain. The MRI shows inflammation and yet we haven't been able to figure out the cause.
Just like when you're working on one of those thousand-piece jigsaw puzzles, if you get stuck in one corner, sometimes it's worth starting at the other corner and hoping that they'll connect. With no answer to her leg pain, let's switch to a different clue that we have from her blood work -- her anemia.
When she came to the hospital, her red blood cell levels were already low with a hemoglobin of 96. But alarmingly, while she has been in the hospital for 3 days, her hemoglobin continued to drop from 96 down to 73. That's a pretty big drop.
Now, when I approach a patient with anemia, one of the first things I look for is the size of the red blood cells because this can be an important clue. For example, if you're low in iron, your red blood cells tend to be small. Whereas if you're low in vitamin B12, your red blood cells tend to be too big. In Jennifer's case, her red blood cells were a normal size, which is also useful information. Since her red blood cells are normal, you then wonder, is her body producing enough red blood cells?
Her doctors ordered a special test called a reticulocyte count, which measures exactly this, how many new red blood cells are being made. Her reticulocyte count was high, which means that her bone marrow is doing the right thing by pumping out extra red blood cells to make up for her anemia.
This really narrows things down. If she is making enough red blood cells, then either she is bleeding somewhere and we just can't see it or something is causing the red blood cells to break up and die early, which we call hemolysis.
Blood tests were sent off to check for hemolysis, but those tests came back normal as well. OK, so we can cross hemolysis off the list, and now we're left with early blood loss. What is happening here? I mean, we can see that she has got some bruises on her legs, but there are no other signs of bleeding. And for her hemoglobin to drop by 20 points means you've actually lost quite a lot of blood. But where is it going?
For now, let's focus on her third and final clue -- her rash. These little red dots are called petechiae and they're caused by red blood cells seeping out of the tiny little capillary blood vessels in her skin. That's interesting, right? I mean, she has got a rash that's caused by little blood vessels bleeding and then she is also mysteriously losing large amounts of blood. These two things must be connected.
Why would blood leak out of these tiny blood vessels? I think that it's either a problem with the blood vessels -- so they're weak -- or there is a problem clotting. Normally, the cells and the proteins in your blood that form a blood clot and stop bleeding aren't working properly.
Now, Jennifer has already had a lot of blood work done, so we're already able to cross off a lot of these conditions. Her platelet levels are actually a bit high, so that's not the issue. Her kidneys, liver, and clotting tests were all normal. On physical exam, she doesn't have any signs of these genetic connective tissue diseases.
The nice thing about rashes is that it's easy to take a sample of the skin and send it to the lab, so that's exactly what her doctors did. They did a skin punch biopsy with a kit like this. All you do is freeze the skin and then push down while turning this round blade, and voila. You've got a sample ready to send off to the lab. This will tell us if there is inflammation in the blood vessels -- like an autoimmune disease -- or a hidden infection. But unfortunately, it takes days, even sometimes over a week, to get the results back, and we can't wait that long. If Jennifer's red blood cells continue to drop further, she is going to start needing blood transfusions.
OK, so we may not know exactly what's going on, but we have done a lot of work to eliminate and rule out important causes. Now we have a relatively small list of potential causes, it's time to go back and chat with Jennifer again [and] ask her detailed questions to try to get to the bottom of this.
When her doctors went back to speak with her, it happened to be around lunchtime, and they noticed that Jennifer left a lot of food on her tray and she wasn't touching it, so they asked her why. She explained that over the last 2 years she has been worried about allergies and intolerances to foods, so slowly she's been restricting her diet and cutting out foods that she suspected were causing her issues. At this point, she stopped eating all fruits and most vegetables without taking any new supplements. Suddenly all the pieces start coming together and her symptoms can be explained by one rare diagnosis, one that many people assume is a thing of the past, and that's scurvy from vitamin C deficiency.
Thinking back, we can explain all of Jennifer's symptoms. She first became fatigued, and there are a few theories about how vitamin C plays into this. Vitamin C is needed to create L-carnitine, which turns fat into energy called ATP. Jennifer's body literally had less energy to work with. Plus, vitamin C is involved in creating norepinephrine, which is very similar to adrenaline, which gives you that fight-or-flight response.
Then there is the bruising and the rashes on her skin. Your body needs vitamin C to make collagen. Collagen is this critical structural support for so many things like your skin, blood vessels, muscles, bone, [and] cartilage. Just imagine how vitamin C deficiency wreaks havoc on your body. Without vitamin C to make strong collagen, blood vessels become weak and they start to bleed easily, which is how you get bruising and that distinct petechial rash that we saw on Jennifer.
Tiny blood vessels heading to the knees also get affected, which explains her joint pains. Now, looking back at the MRI of her legs, we can connect the dots. Scurvy leads to abnormal connective tissue, and that causes the fascia, the tissue, and the muscle to bleed. Our body does not like blood in those areas, so it leads to this huge inflammatory response. Part of that is fluid buildup, and that's what we saw in the MRI. All that inflammation from the blood caused the pain. It also explains why her hemoglobin kept dropping and why her blood work suggested she had early blood loss even though we couldn't see her losing blood anywhere.
Siobhan Deshauer, MD, is an internal medicine resident in Toronto. Before medicine, she was a violinist, which is why is called Violin MD.