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- [00:00]
Podcast Host
Welcome back to Run the List, a medical education podcast in internal medicine. As a quick disclaimer, this podcast is made for educational and informational purposes only and should not be understood as medical advice under any circumstances. Before we get to the show, a quick word on the sponsors for today's episode.
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Co-host or Sponsor Representative
This episode is brought to you by Open Evidence. Open Evidence is a really incredible resource for people in medicine. It's an AI powered medical information platform that can help you answer clinical questions, provide high quality literature and and so much more. You can ask questions like what are the classic imaging findings for gout? Or tell me about the landmark trials in lupus nephritis. They recently partnered with the New England Journal of Medicine so they have access to their text, figures and tables within Open Evidence. It's free and unlimited for healthcare professionals, so I highly encourage you to go check it out. Go to openevidence.com to learn more. I'm so excited to welcome today's guest, Dr. Michael Pillenger, whose long list of titles and accolades might take more time than we have today. But in brief, he's a professor of medicine at NYU and director of the Rheumatology Fellowship here as well. He's also the chief of Rheumatology at the VA in Manhattan and really just a phenomenal teacher who is beloved here at nyu. He has a particular interest in gout with, which is the focus of our episode today. So we're actually gonna split this topic up into two parts. The first being the presentation of gout and the initial workup, and then the second episode focusing more on treatment both in the acute setting and then also in the outpatient setting. Dr. Pillenger, thank you so much for joining us here today.
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Dr. Michael Pillenger
Thank you, Dr. Gutaski. It's a really great pleasure to be here with you.
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Dr. Gutowski
All right, so let's get into our case. Today we have Mr. G. He's a 55 year old gentleman with a history of hypertension and hyperlipidemia and he's coming to the emergency room with severe pain in his big toe. He says that his pain started yesterday and it's been getting worse and worse overnight with the toe becoming swollen and red. He tells you that this has happened before a couple times, once in the same place. But sometimes it also affects his knee, sometimes the middle of his foot. And he's not exactly sure what's causing it, but he thinks his dad might have had the same problem. Usually he'll take Tylenol, ibuprofen, or he'll put some ice on it, and it'll go away within a week or so. But this time the pain is really intolerable, and his wife is insisting that he get seen taking a look at his vitals. They are notable for a temperature of 99, a heart rate of 94, blood pressure of 145 over 90. He's clearly in pain and does not allow much of an exam. But just by looking at him, you can see a big, red swollen toe. But then, unfortunately, he gets whisked away to radiology for his X rays. So you go to the computer, you take a look at his chart, and you see that the emergency room has already obtained a set of basic labs as well as inflammatory markers. His CBC and CMP are within normal limits, but his ESR is elevated to 65 and his CRP is 12. They've also ordered a uric acid level, which is pending. So, Dr. Pillenger, how does this patient's history and presentation sound to you?
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Dr. Michael Pillenger
Well, Dr. Gutowski, you set me up for what sounds like an easy swing on a pitch, but it should never be considered easy when you're at the level of a patient. Right. So there are many classic features here for the disease of gout, which is mostly what we're here to talk about today. But if we break those features down, the differential diagnosis is going to be wide. So what am I really talking about here? There are a couple of important and salient facts. One of the facts is speaking generally is he has joint pain. So this is, in fact, an arthritis, and it's acute. So it's an acute arthritis, and it is swollen and red and it hurts. And so this is also inflammatory. I want to remind our listeners that. That we've worked really hard to get as far as we have in medicine, but some things don't change. If we go back, oh, about. About 2,000 years, we'll find the Greek physician Celsus, living in Rome, who was the first person to give a formal definition of inflammation. And what was it? Many of you know it was Calorubor, dolar et tumor, heat, redness, pain and swelling. And so I. I don't remember whether the joint was hot, but he has all of those things. And so this was the clinical impression of inflammation. So what have we got? We've got a monoarticular inflammatory arthritis that came on rather acutely. And this is a big setup for gout, or for a gout flare, allow me to say, but also a setup for a number of other potential diseases that are nearly as likely at this Point one of those is calcium crystal disease. Gout is a crystal disease. I think we'll talk about that. And any crystals can cause kind of the same effect. But the most important thing we want to be concerned about is in fact, the possibility of infection, because infections come on acutely. They're red hot, swollen and painful. And what's really bad about missing an infection is that infections damage or even destroy joints. So missing or failing to consider that diagnosis would be a real, kind of a real sin, frankly. There are other things that could be. But I won't go on. At length. One thing that's very important though here is that it's severe pain in the big toe. And as some of our listeners may realize, gout is often a disease of the big toe and certainly first attacks, and this is not a first attack most commonly happen in the big toe. Why that is, it's kind of interesting without a definite full answer, but that fact alone tips the balance here towards an acute gout flare without completely ruling out the other possibility. So that's kind of where I would stop, unless you have other thoughts yourself.
- [06:25]
Dr. Gutowski
I think that was a perfect discussion of the differential diagnosis here. And I think moving forward, we'll assume that we've confidently ruled out these other causes of monoarthritis. Since we are discussing gout today, why don't we take a little step back and go back to the basics? And I know, Dr. Pillenger, you enjoy talking about the basics and the complexities of gout. Can you kind of give us an overview of what exactly happens in the body during a gout attack and what causes gout?
- [06:53]
Dr. Michael Pillenger
Yeah, I'd be happy to. Not just the basics, but the beginning. So I've already told you about the Greek physician Celsus, but even the earlier the Greek physician Hippocrates knew about gout. So this is a very old disease, and the core basic facts of it have become pretty straightforward over the centuries. The actual biology is a lot more complicated. So what are the basics? Gout is a crystal disease, and it starts therefore with the formation of crystals. And much like any of you listening, if you ever made rock candy when you were a kid and you put too much sugar into solution and supersaturated it, And I was taught to tie a string to a pencil and drop the string into the glass or the beaker, crystals form here. The source of crystals is in fact monosodium urate, or uric s. And so this is a disease of uric acid, first as hyperuricemia, which has Its own biological implications. And then as the formation of crystals. The formation of crystals is complicated. It is basically about supersaturation. But there are people walking around, people listening to us right now, whose serum urates, and urates in their joints are high and are not forming crystals, and others who are not that high, but high enough to form crystals. So we have to start with this concept of hyperuricemia that leads to urate crystallization. Hyperuricemia is its own set of complexities. When you sort of peel the onion back like. Like Donkey and Shrek, right? When you start to look at how hyperuricemia happens, there's a lot of biology there. And in fact, this disease goes back more than 2,000 years. It goes back 20 million years to a set of mutations which are uniquely human, although shared by primates. And that's because back then, while we were metabolizing our purines into actually allantoic acid to get rid of them, a mutation happened. And that mutation blocked the conversion of this molecule, uric acid, which is basically a purine derivative, into a molecule called allantoic acid. What happened? Two things happened, as far as we know. The first one was it probably helped us survive. And I won't go into too many details, but one of the things it probably did was keep our blood pressures up. It's thought that soluble serum urate, as raised by that mutation, may have resulted in the normalization of blood pressure. Certainly it can be shown to do that in rats and in human beings, urate can be shown to be a contributor to hypertension. That can actually be reversed in some studies by lowering the serum urate. So we started thinking it 20 million years ago by raising this urate very close to the point where these crystals form, but not quite there. And after that, other things have to happen. That's where we are. But then if our urates go above the level of solubility, which is 6.8 milligrams per deciliter, they become susceptible to crystallization. And this happens in a lot of people, about 30 million people in the United States alone. Why does it happen again? Peel it back. And it gets complicated. Some of it has to do with sex hormones. And so men post puberty have higher urates than women post puberty. Women after menopause have urates go up. And so somehow sex hormones regulate the production, or more likely, the excretion of urate. And so we men tend to be at risk for higher urate and therefore at higher risk for gout. On top of that, we're going to add in foods that may be high in urate, conditions that may cause urate to be overproduced, and kidney diseases that make urate hard to get rid of, including some genetic mutations that don't look like kidney disease, but raise the serum ureate levels. And when you put all of that together, some percentage of humans will have a urate high enough to start to form those crystals.
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Dr. Gutowski
That is a fascinating history lesson, bringing us back to the 21st century. Taking a look at this patient and typical patients with gout, what elements of their history, exam labs and or imaging, can we use to help clinch the diagnosis?
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Dr. Michael Pillenger
Yeah, so that's great. So he has all sorts of things going for him. He's male, he's 55 years old. Hippocrates pointed out that gout doesn't start in men until after puberty, but the prevalence goes up over time. He has hypertension. I will bet you he has a little bit of low level kidney disease. Even though the CMP is within normal limits, he's got all of the right parameters to be patient with gout. Now, how do we look at him, though? We look at him in the setting of what he cares about. What he cares about is that his toe is killing him. And why did that happen and how did that happen? Well, the easiest metaphor here is just that once these splinters appear in your joint, they're really tiny, they're microscopic. But imagine 10,000 little wood splinters in your joint. You'd have a really acute inflammatory reaction. And these crystals are actually designed in a number of ways to really provoke inflammatory reactions. These attacks come on very quickly, which is very characteristic of gout. And that's what this patient has had. They resolve and then they recur and they're just exquisitely painful and they tend to come on at night, which also happened to him for reasons that we don't understand very well. It's very interesting. It could be circadian rhythms, changes in blood ph, changes in blood volume, something we really don't know very well. Anyway, Mr. G doesn't care about any of that, does he? He wants to feel better. And so that's what we're going to need to address if we're going to make him feel better.
- [13:36]
Dr. Gutowski
As I mentioned, he doesn't really allow much of an exam. You see a big swollen red toe. But if he were a patient who did allow an exam, or a patient who was seeing you in clinic, not during an acute gout flare, what kinds of things are you looking for on your Exam that might tell you that this is a patient who has a diagnosis of gout.
- [13:54]
Dr. Michael Pillenger
Yeah, it's certainly easier in the big toe because it's a little more available. But this is a disease, I want to say, that can affect virtually any joint. Toe most common midfoot and ankle common, knee common, but also the upper extremities. I can certainly look for deposits of uric acid, monosylvium, urate, elsewhere in the body. That would give me a hint that this was gout. We call these Tophi. They tend to be late in disease, but not always. So we should always look for, for them, a classic place for them that's easy to see is actually on the top of the ears, also at the elbows and sometimes at the metacarpal phalangeal joint. So if you see those, you're going to be very confident that this is a gouty attack. Then we're going to look at the labs and the X rays, which I know are pending at this point. Unless we want to assume that they've gotten back.
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Dr. Gutowski
Yes, you've just been notified that the uric acid just came back at 5.7. So. So taking that into account with the elevated inflammatory markers, can we talk a little bit about this patient's labs as well as labs in general in gout patients?
- [15:04]
Dr. Michael Pillenger
You bet. Every patient that I see with gout, I always get a cbc. I always get at least a metabolic panel, and I always get a sedimentation rate and a C reactive protein, and I always get a uric acid level. The reason we're doing this is not necessarily to unequivocally define gout, but to try to lend support to gout or possibly to put some weights on the non gout side of the diagnostic scale. Now, a lot of these things are less helpful than we would like them to be, quite honestly. So, for example, we're going to get a CBC primarily because if the patient has an infected joint is more common in large joints like knees than toes, but they're likely to have an elevated white count. What about gout? Well, it can be a highly inflammatory disease, and sometimes the white count is elevated in gout patients, too. Not as high as an infection, but there's no line here. And so we have to use judgment, interpreting the level of the white count. I'm going to look on the metabolic panel for one thing. I'm going to see if there's an acidosis, because that could imply infection. But one of the confusing things about gout is that things like infection that cause Acidosis actually tend to spur attacks. So sometimes patients have more than one thing. Life's not simple. The other thing I'm looking at is to define a level of renal insufficiency. And again, there is no hard, fast rule here. But patients with renal disease tend to have higher urates, tend to be at higher risk for gout and gout flares than patients who don't. Now, what about that sedimentation rate and the C reactive protein? Well, gout is a highly inflammatory disease. In gout, patients often have very high sedimentation rates, very high C reactive proteins. It is not uncommon to see a sedimentation rate above 100 in a patient with gout. So these are highly inflammatory states. The problem is that so is a septic knee, for example. And so these labs don't help us that much distinguishing gout from infection.
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Dr. Gutowski
In this case, this patient doesn't have a visible or at least large enough effusion to be able to aspirate. But sometimes we'll see patients come in with a big swollen knee and ask them if we can put a needle inside their knee. So what are we looking for there?
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Dr. Michael Pillenger
Yeah, so that is the most important thing to do for patients. And there are several reasons why we may not do it. One is we may not have the skill to do it. We rheumatologists, we're trained to do this. Orthopedists are trained to do it, but maybe one of us is not available. So sometimes it's just not feasible. A lot of the time, the patient says no. And so the patient saying no is another reason not to do it, obviously. And the third reason is sometimes you remain unconvinced that there is, as you say, Dr. Gutowski, an effusion to aspirate. That is mainly true in a small joint with gout, such as this first MTP that Mr. G has. It's almost never a reason not to aspirate a joint like the knee. And we aspirate both to diagnose gout and also to rule out other things, once again, especially to rule out infections. So what are we looking for when we take the fluid out? Well, if it's inflammatory, we expect to see leukocytes, usually neutrophils, polymorphonucleotide neutrophils. And these can range from somewhere above 3,000 neutrophils per cubic millimeter, all the way up to. To 200,000. And these are ranges that you also see in infected joints. Now, infected joints tend to be on the higher side. If a patient has an aspirated joint and the white count is above 50,000. It remains our burden to prove that it's not infected. What else are we looking for, though? Well, we're looking for the presence of those crystals and we use a polarizing microscope to make it easier to see those crystals or other crystals, such as calcium based crystals. Then we go looking for the infection. And even if we see crystals, we still give consideration to the infection because they can occur at the same time. So it's pretty simple. A gram stain and a culture. And if the white count isn't too high and the gram stain is negative, you are in pretty good shape. If the gram stain is negative but the white count is very high, you are probably going to wait for that culture to make a definite decision. And so again, we always have to contextualize. This is the joy and the dilemma of practicing rheumatology. I don't have a single test that gives me an unequivocal answer. Everything is interpretation. So for the past decade or so, we've had the convenience of classification criteria for gout. Not for gout flair, but for gout. And there's a distinction between diagnostic criteria and classification criteria. Classification criteria are a set of rules that a bunch of big poobahs sitting in a room have made to enter people in studies. And so they're more specific than diagnostic criteria. And in rheumatology, we mostly don't make diagnostic criteria. But if a patient meets classification criteria, we can have a fairly high degree of certainty that they do indeed have the disease of gout. They may have gout even without meeting those criteria, but we will be left to our judgment to make that diagnosis. And so if you want to know what these criteria are, a lot of them look like the things we've already described. Does the patient have a history of one or more of these attacks? Have any of them been in the toe? Have they come on quickly and gone away fairly quickly with treatment? What do the X rays show? Or ultrasound or dual energy CT which lets us look at urate? Do they have those tophi? We look at all of these things and you can add up the points and see if you get to such a diagnosis. There's no doubt that Mr. G, if we added up those points, would make it. If you just Google gout classification criteria calculator, you can actually plug your patient in. If the patient meets those criteria, they could have gout and an infected joint today. This doesn't mean that this is gout, but at least we know they have Gout, and we can decide whether this is a gout flare or something else.
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Dr. Gutowski
Thank you for taking us through that. You mentioned imaging as part of our classification criteria. I want to just briefly go over some of the imaging modalities that we can use both in a chronic case of gout and also in a gout flare.
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Dr. Michael Pillenger
So imaging is much more valuable for defining the chronic case of gout than for diagnosing the gout flare. Therefore, to see things that are convincing for gout, it often requires a patient in a fairly late stage of disease, at least, at least several years of gout without treatment. So what are we looking for? Well, this patient, Mr. G, rolls into the ER and we get a foot X ray. If there's nothing else, we'll see on the X ray what we see in the er, which is soft tissue swelling. The footprints of gout will be different. And one of the footprints of gout is the development of urate deposits, tophi, which is a word for stone within the bones under the cartilage. And so we see these in soft tissue I mentioned in the ear, but they also appear in the bone and they destroy the bone. And they have a characteristic look that we call a punched out lesion. And that looks almost, almost literally like a hole punch had gone right near the edge. Very characteristically, there's what we call an overhanging edge, which is almost like the top of this gouty lesion has popped open. That is really pathognomonic for a chronic state of gout. It's just not always seen in everybody. But in poorly treated patients, it will be very common. X rays take us only so far. Ultrasound is increasingly valuable. You need an operator who is good at it and can interpret it. You may have a radiologist who can do it. Many rheumatologists are trained to have a good look. And there are several things you can see when you use ultrasound. One of the most characteristic is you can see those tophi, those lumps of urae. Another is something called a double contour sign. What this is is a deposition of urate on the cartilage surface within the joint, almost like icing on a cake. And over a number of years, with a high urate burden, urate will precipitate on the surface of the cartilage and ultrasound can see that. And then finally there's something called a snowstorm sign, which represents urate within the joint. Often seen during flares, but sometimes in between flares looks a little like static on an old black and white television. There's just stuff in there. So ultrasound can be very, very helpful. I think the favorite imaging of gout clinicians everywhere is dual energy ct. Some of our listeners may know about dual energy CT as used for looking for kidney stones. Dual energy CT technology is not in every hospital, unfortunately, but we can use this to actually look directly for urea deposited in the joints or the tissues. And that's an unequivocal way for us to define urate. And you get these fantastic pictures with these basically these green lumps of urate. It's gone past being experimental, but it's certainly not universal. And it's not needed in a setting like this to know that this patient was going to need to be treated.
- [25:50]
Co-host or Sponsor Representative
This wraps up the first part of our two part series on gout, focusing on the initial presentation and workup. Part two, we'll focus more on treatment, both of this acute flare. And then we'll also meet our patient again when he comes back to see us in clinic. We'll talk about urate lowering therapy and how to prevent him from having a flare like this again. So definitely come back and join us for part two. Until then, thank you so much, Dr. Pillenger, and we will talk to you soon.
- [26:27]
Podcast Host
Some content from this episode was generated with the assistance of artificial intelligence.