What is Gout and How is it Treated?

Rheumatologist Dr. Manish Jain joins Cardiologist Dr. Michael Koren to break down what gout is, why it can be one of the most painful forms of arthritis, and why it can affect far more than the big toe. Dr. Jain explains gout's metabolic underpinnings, the role uric acid plays in the disease, and how systemic complications can affect the kidneys and beyond. The doctoral duo then discusses what uric acid levels mean, why some uric acid results may be misleading, and how important it is to control these levels for a gout patient. The duo finishes by reviewing standard treatments for gout, the importance of "not killing the patient to treat gout," and new treatments on the horizon in gout clinical trials.

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Transcript

Welcome And Meet The Guest

Announcer 0:00

Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts, hosted by cardiologist and top medical researcher, Dr. Michael Koren.

Dr. Michael Koren 0:11

Hello, I'm Dr. Michael Koren, the executive editor for MedEvidence! And we like to do something to help our patients understand disease processes better. And I'm really privileged to have Dr. Manish Jain to talk to all of us, including educating me, about gout, which is something that a lot of our patients have wondered about. And I think there are a lot of misconceptions out there in terms of what is gout, how do we treat it, and what's on the horizon to make the treatment even better. So, Manish, welcome to MedEvidence. Thank you for being part of this. And I'm really interested in picking your brain today about what the heck is gout and how do we do a better job of treating it. So, again, just uh introduce yourself real quickly in terms of who you are and your role, and we'll get right into it.

Dr. Manish Jain 0:55

Yeah, absolutely. So, my name is Manish Jain. I'm a Chicago-based rheumatologist. I'm in my lucky 14th year of practice, and I've cared for many, many, many patients with gout in that setting. I also uh am a clinical trialist. So I help run studies to bring new treatments to our patients as a care option for many diseases, including gout. So again, thanks so much for having me here.

What Gout Really Is

Dr. Michael Koren 1:20

That's great. So let's just jump right in. So, what the heck is gout? Explain to our patients what that really means.

Dr. Manish Jain 1:26

So, yeah, as a rheumatologist, I've you know had the pleasure of taking care of many, many, many patients with gout. There's probably a lot of people listening to this right now who've either been directly touched with gout or have had family and friends touch with gout. So, gout is actually the most common form of inflammation in the joints. We all know gout or kind of probably know it when we see it, right? Think about that red, hot, swollen, big toe. It's one of the most exquisitely painful maladies. It's actually used to be known as the disease of kings. Because we used to think that, you know, a diet played a huge, huge role in in gout in a diet like you know, like a king would drink red wine and eat steak. So most common form of joint inflammation. And it's a condition that we've actually recognized has a lot of systemic [issues]. So really, you know, problems that extend beyond the joint and into the heart, the kidneys, and you know, other systemic uh issues. So gout is driven by a crystal that's just a byproduct of being alive. It's called uric acid. And what happens with uric acid is it starts to deposit in the body, it deposits in the soft tissues, in the joints. And over time, the more of it that's kind of in the body, it can start triggering really uh uh troublesome attacks that can be really, really debilitating. So anyone who's you know listening to this who's struggled with a gout attack might resonate with it's really hard to live your life when you're having an active gout attack, red, hot, swollen joints, difficulty with mobility, difficulty just getting through your day. So yeah, that's gout.

Where Gout Strikes Beyond The Toe

Dr. Michael Koren 3:07

Yeah. So let me ask you a few questions about that. You know, we hear about a big toe hurting, and I think that's most people's perception, but it sounds like it's more than just the big toe. Can you tell us what other joints are affected and how often it's the toes versus other joints?

Who Gets Gout And Why

Dr. Manish Jain 3:20

Yeah, great question. So the most common place where we'll see gout attacks over time tends to be in the feet and in the hands. And that's because the feet and the hands actually run a little cooler than the core body temperature. And some of that coolness actually helps the gout crystals deposit a little bit more inside those extremities. But gout can affect any part of the body. Believe it or not, gout's actually a recognized cause of acute gout pain, uh, of acute back pain. And so we we actually have had patients in my practice, there's patients in the literature who have episodes of back pain. In the setting of gout, you treat the gout and they have less episodes of back pain. So, really, all that to highlight that any joint can be involved, starts off most commonly hands and feet, but as you let the disease kind of go on over time, there's there's no end to where it can attack the body.

Dr. Michael Koren 4:17

So, Manish, is this a disease of younger people? You said it was a disease of kings. Is this kings that are in their final decade of life? Or is it when they're brand new kings? Just give us a little bit of a men versus women. How about queens? Is it a disease of queens?

Dr. Manish Jain 4:31

Yeah. No, so you know, actually, um let's start with gender. So a third of our gout patients are women. That actually really surprises a lot of patients. In in women, gout often looks and feels a little bit different. It tends to be more postmenopausal. And it's because estrogen, as it drops over time, actually, estrogen is protective against uric acid. So as the uric acid levels go up over time. And and the pearl that I learned from you know, my my teachers and the one I still see in clinic every day is uh gout loves to hide in my my postmenopausal uh female patients' hands. So sometimes I'm looking at really lumpy, bumpy hands, and I'm just like, wait, is this just good old-fashioned wear and tear arthritis, osteoarthritis, or is there maybe some gout in these hands? In men, certainly you see a spike related to age, but but actually I see a lot of young patients with gout. My my average gout patient is a young male with with gout who's seeking specialty care. And it it just goes to show you that, you know, gout's often really not driven by by diet. Very common thing for me to mention in clinic to a, you know, let's say a 40, 35, 40-year-old guy, you're eating and drinking everything your buddies are eating and drinking, you're getting gout, and they're not. So it shows us there's this metabolic cause that's driving it for most of our patients.

Dr. Michael Koren 5:50

And statistically, would you say the feet and hands are 90% of it or 10% of it?

Dr. Manish Jain 5:56

Yeah, no, that's great. So 90% of gout patients in their career will have some degree of foot involvement. So overwhelmingly, have I seen some folks where it really started in a knee? I have. Have I seen some folks where it started in a in a different joint? I have. But again, hands and feet tend to be that most common. Probably another 90% of patients are going to have that effect.

Dr. Michael Koren 6:15

And symptoms you mentioned are pain and swelling. Anything else that is specific to gout versus other forms of arthritis, for example?

Dr. Manish Jain 6:23

Yeah, pain, swelling, loss of function. You know, I describe gout to patients as a habanero pepper. I have other diseases like rheumatoid arthritis, psoriatic arthritis that are a little bit more of like a jalapeno rather than a habanero. But gout's a habanero. It's red, it's hot, it's fiery. And again, these are patients in in real need of very urgent help.

Uric Acid Causes And Diet Myths

Dr. Michael Koren 6:46

Got it. So you mentioned the cause is uric acid. Is it always uric acid? I know in kidney stones, you can have uric acid stones and other stones, but how about gout?

Dr. Manish Jain 6:55

Yeah, gout really is driven by this single crystal, this single problem of high uric acid. What we've learned about more is there's many routes to a high uric acid. So, what what we used to do as a medical community is just admonish our patients for bad diet with gout. We know that you know, certain foods, alcohol, you know, anything, uh, steak, seafood, shellfish, believe it or not, Coca-Cola. So the fructose in Coca-Cola actually helps promote uric acid. What we've learned over time, though, is that yelling at patients about diet is actually a very low quality intervention. And now where our thinking is is listen, diet's a part of it, and we want to focus on diet, but but it's a lot of metabolic issues. You know, there's genetic issues where folks are inheriting or acquiring genes, they're just not peeing out uric acid correctly. And so, you know, we're we're getting to a point where we're yelling at patients less about diet and recognizing it as a core metabolic issue that that has its own types of treatment.

Dr. Michael Koren 7:58

Okay, so you so you're not using uh physical tactics in addition to yelling at patients.

Dr. Manish Jain 8:04

Exactly. Exactly.

Dr. Michael Koren 8:05

We're using now better psychology and better medicines. Yeah, yeah.

Dr. Manish Jain 8:10

And again, diet lifestyle plays a role.

Dr. Michael Koren 8:11

I'm joking, everybody.

How To Read Uric Acid Labs

Dr. Manish Jain 8:13

Yeah, diet lifestyle plays a role. Don't want to underestimate that, but but you know, by the time a gout patient gets to my office and they've had a couple flares in in a year or or more, or they have other signs of serious gout, other signs are what we call TOPHI, T-O-P-H-I, where you actually get the hard uric acid deposits that are starting to actually form large accumulations of crystals that could be in the feet, in the hands, in the elbows. I call them lumpy bumps. Like how many lumpy bumps do you have from your gout? And and they do damage actually, they erode into the cartilage, into the bone. So, you know, there's there's a number of these issues that the uric acid crystal itself causes.

Dr. Michael Koren 8:57

Now, when we draw a routine laboratory test, blood test, we get a uric acid back. Is there any level of uric acid back that will predict gout or that will certainly cause it in most people? Or explain a little bit more about those levels.

Dr. Manish Jain 9:12

Yeah, will do.

Dr. Michael Koren 9:12

So how do we manage that?

Dr. Manish Jain 9:14

Yeah, great question. So high uric acid predisposes to, but doesn't equal gout. So meaning, like if a patient has an elevated uric acid level, I'll kind of go through those levels in a second, that patient is going to be at higher risk for gout. Let's say you just have a high uric acid and you haven't yet had a gout attack. We call that asymptomatic hyperuricemia. So we're on call, right? And that's again where we're pushing diet and lifestyle and weight loss and you know, taking a hard look at a patient's medications, but we're not necessarily jumping in with special gout treatments at that point. Any level with uh serumuric acid level above six means that your body has a net influx of uric acid into it. So any level above six technically can predispose a patient over time to gout. The higher the number, the greater the risk. So if I'm looking at a patient with a uric acid level uh in the nines and the tens, is that is that milligrams per deciliter? Just just exactly milligrams per deciliter. So it if I'm looking at a level in that range, my average patient actually has a 10% year-over-year risk to develop gout. That's pretty high. And there are a lot of folks out there living with uric acids that high.

Dr. Michael Koren 10:30

Right. Now, if you have a sort of normal uric acid level, let's say four, does that prevent gout all the time, or do people still get gout at with normal uric acid levels?

Dr. Manish Jain 10:41

Yeah, great question. So peep I have seen gout with uh with normal uric acid levels. There's a couple of reasons for that. So, first of all, some people just continue to deposit, you know, not every patient reads the textbook. So, you know, there are some people that kind of can deposit uric acid even at slightly lower levels. But I'll tell you, one of the most common things I see though is uric acids most often checked in the setting of a gout attack. It's just like the most common time, but doctors are thinking about gout and checking it. When uric acid's checked during that acute red-hot habanero flare, it often is falsely low. It's actually low in about 50% of patients. And in the way I kind of describe it to patients, it's hiding in your joints. So we're not picking it up in the blood. It's actually a little more complicated, but when we see acute gout and have a lot of inflammation from acute gout, your one of your body's responses is actually to pee out the uric acid in response to that inflammation. So, anyway, uric acid levels, not very reliable in the setting of that acute gout attack. I often will have to wait two or three weeks after the acute gout attack is resolved to get the truest sense of where where the uric acid lives.

Long Term Control With Allopurinol

Dr. Michael Koren 11:52

Interesting. So tell us about the treatment.

Dr. Manish Jain 11:54

Yeah, so a lot of treatments, right? And again, don't want to downplay diet and exercise and and uh lifestyle changes are really important. You know, I've seen some patients really do well with with diet and lifestyle alone. A minority, you know, really a minority. I've had patients with massive amounts of weight loss, you know, let's say, you know, hundred-pound weight loss, where I've really seen gout kind of exit that patient's life. I've had patients who really consumed a lot of alcohol and then, you know, went to teetotaling. And so that I've seen some dramatic improvements. But again, really low on my Rolodex of patients over 14 years. My my average patient in the long run is going to need some type of medication to attack gout at its root and and to actually start eliminating or at least decreasing the production of uric acid over time. We have a lot of conventional treatments out there. The most common one is called allopurinol. And so allopurinol, great drug. Been using it forever. It's our first line treatment. We have some issues with allopurinol, though. Allopurinol, at the most commonly used doses that doctors feel comfortable outside of a specialty setting of writing for the drug, probably only gets about 50% of our patients to their goal, uric acid. And so we have some gaps in care, and that's why it's important that we have new medications that we're bringing to the forefront to help out patients.

Dr. Michael Koren 13:20

Now, I was taught, I don't know if this is still considered true, is that using allopurinol during an acute gout episode is probably not a good idea. Is that still the thinking?

Best Meds For Acute Flares

Dr. Manish Jain 13:33

That's my thinking. So, yes, you know, the uh uh so the problem with mucking around with uric acid during an acute flare is you're you're pushing uric acid in and out of the joints. And so you would what happens, you know, we we get concerned that we may prolong a gout flare by starting allopurinol during the flare. The problem on a population health level is we stink at getting patients on allopurinol and dosing it correctly over time. So, where our guidelines have gone is to get allopurinol start. Patients in the hospital, they're having gout flare, start the allopurinol with the hopes of capturing more patients. We have some low quality emphasis on low quality data to show that, oh, maybe it increases the gout flare a little bit, but doesn't meet statistical significance. That being said, in my practice, decades and you know, decades of conventional wisdom, you know, from from seasoned docs like yourself, Dr. Koren, yeah, we I typically am loathe to start out purol during an acute flare. What I do use that acute flare is as a great education point for the patient. Statistically, you're gonna be in my office again having a flare. We've got to do something about this. This is no way to live. Let's get your acute gout cooled down and then start to work on it. And we work on it by working on the uric acid.

Dr. Michael Koren 14:56

Excellent. So tell us just about some of the things you do for the flare symptoms themselves. I assume it's typical anti-inflammatory type agents. So, but why don't you break that down? Are there some that are better than others for the acute flares?

Dr. Manish Jain 15:09

Yeah, we we've got we've got a little bit of new stuff for flares, but but it most of it is pretty conventional. We we have kind of three classes of medicines, and I'll go in kind of descending order of how I'm using them in my clinical practice. So I used to say, oh my gosh, anti-inflammatory, non-steroidal anti-inflammatories were the first line treatment. We've actually moved away from that a little bit. So we've found that systemic steroids, which are have their own problems with long-term use, but in the short term, right? You think about like a medrol dose pack, a six-day steroid dose pack, actually is non-inferior to and better tolerated than the non-steroidal anti-inflammatories. There's a Cochrane review about that, maybe five, six years ago, that kind of help uh bring that to light. So my average first-line treatment is going to be just a steroid, you know, some type of a steroid. Occasionally I'll inject it. More commonly, I'll just give it systemic because when I give it systemically, it it kind of gets into the soft tissues. I'm more confident rather than just pumping it into a single joint. So that's typically where I start. But, you know, I have to think about the whole patient when I'm selecting the treatment. If I have a patient who's a diabetic and especially one who's having issues around blood sugars, I'm gonna skip the steroids. I work a lot with training doctors. And so the first thing I teach them is don't kill your patient to treat their gout, right? So we got to think about the whole patient holistically and use the other comorbidities to kind of help drive what we're selecting. So, all right, so let's say the patient's not right for steroids. My second line treatment is non-steroidal anti-inflammatories, the the you know, medicines like ibuprofen and and neproxin. The classic one that was studied was Indomethacin. It's where the first studies were done. There's nothing special about Indomethacin. Every, you know, every other non-steroidals have have worked. But but again, as I teach my trainees, if a patient's got a little bit of kidney disease, don't use a little bit of an NSAID. Move on to a different therapeutic option. All right, we we cannot kill our patient to treat their gout, right? So we got to think about the whole patient. My third line agent is a drug called Colchicine. Colchicine's a pretty good drug in other phases of gout. I use it a lot for prophylaxis, and we can talk about that in in a few minutes. For acute gout, it's just okay. You know, it's it's usually is the reason it's my third line. And then we have some advanced therapy. Actually, Dr. Koren, this lives in your world, canakinumab. It's a uh biologic that blocks interleukin one. Some really interesting data about heart disease prevention in the, I think it was the Cantos trial. But we we use it in acute gout, and it's an incredible drug for acute gout, really effective when I can't use steroids and I can't use NSAIDs. And then I have those patients, right? If I have a patient with kidney disease and and diabetes, which describes a lot of my patients, that that might be a patient I'm reaching for canakinumab.

Dr. Michael Koren 17:58

Got it. Narcotics, I assume, are just masking the problem. You don't use those, is that correct?

Dr. Manish Jain 18:03

I I don't. Yeah. And again, I'm all for whatever makes patients feel better. I I can't say I've ever met a patient five years into prescribing narcotics, that that uh thank you, doctor, for that thoughtful decision. But yes, yeah, typically, right, I'm using one of those medicines that I mentioned, but a lot of education that this is going to keep happening, it's gonna keep getting worse. The attacks are over time gonna get harder to break unless we act at the primary problem.

New Gout Drugs And Trials

Dr. Michael Koren 18:28

Excellent. Now you mentioned that you do a lot of work in clinical research, as do I. So you're state of the art. You know what's coming down the pike, as they say. So, what is on the horizon for the treatment of gout? What do you what do you predict we'll be seeing over the next two to five years?

Dr. Manish Jain 18:43

So, because gout is so common, and because we know we're overall doing kind of a cruddy job of treating it in our population of patients, there's actually a lot of development that's that's coming out there. A little bit is in the acute flare realm. So I referenced that canakinumab, that advanced treatment that we're using. The issue with canakinumab, it's it's an injection. So, in the pipeline, there are studies looking at oral versions of canakinumab, which again might be a little bit easier to treat that acute gout. Where we're also seeing a lot of innovation is in medications that will help drop the uric acid. And so there's actually three trials I have going on right now at my research site in Chicago. Two are for an oral agent called deniterad. And so deniterad is a new take on an old medicine. The old medicine's probenicid. And what probenicid does is it helps, it helps prevent the under-excretion of uric acid. So it's allowing the body to better pee out uric acid. Uh, probenicid's just an okay medicine. It's not all that effective. And so dotinurad is like a super probenicid, very, very effective. It's already approved in other countries, and we've seen rates of like 90% treat to goal with it. So we have two studies going on right now for that at my Ravenswood site. We we have another take on maybe a slightly older drug. The older drug is called Pegloticase. It's it goes under the brand name Krystexxa. And Kristexxa is a really potent, really powerful drug that rapidly helps clear uric acid in the body. The problem with Kristexxa, it's an every two-week infusion. It's hard. I take that corner, I take care of patients who work. And so, as I'm sure you do too, and it's it's hard, right? To come in and you give up your work a half a day from work to come into my office and get an infusion. So we're actually studying the subcutaneous version, a version that a patient could do at home. So really, really exciting and just, you know, it it's good to have good drugs, but if you don't have good drugs that patients can actually take, what are we doing? Interesting.

Dr. Michael Koren 20:47

Yeah, those are the studies that's much more an effective drug that becomes much more convenient and accessible for patients when they can give themselves subcutaneously. Yeah.

Final Advice And How To Learn More

Dr. Manish Jain 20:55

Absolutely.

Dr. Michael Koren 20:56

Cool. Exciting stuff. Manish, any final words of wisdom for people listening in on us about gout and and how they should approach it?

Dr. Manish Jain 21:06

Yeah, I would say think about gout as a systemic disease. And you know, we didn't get as much into the you know the heart and sort of the kidney risk, but really feel like it's a systemic disease that that deserves your full-time attention and not just the attention during the flares. If you don't feel like your gout care is going the way it needs to go, a rheumatologist can certainly be helpful. And just a lot of advanced treatments, a lot of great opportunities, not just to potentially help yourself with gout, but to help all patients with gout.

Dr. Michael Koren 21:37

Manesh, this has been delightful. On behalf of our listeners and our viewers, thank you for this information. And uh, for those of you that may be interested in clinical trials, there'll be some connection with this podcast so that you may find a center near you that is looking at this issue through an expert clinical trialist. Thank you very much.

Announcer 21:57

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