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Gout, the most common form of inflammatory arthritis, can wreak havoc on the body. The good news? It’s easily managed with the right help. Whether you’ve been recently diagnosed, care for someone suffering, or are a medical professional treating the disease, the Kicking Gout in the Acid podcast can help you learn more about how to manage gout.
In this episode of Kicking Gout in the Acid, Dr. Larry Edwards is joined by Gout Education Society International Advisory Council member Dr. Herbert Baraf, Senior Clinical Advisor at the National Institute of Health, educator at George Washington University and former practicing rheumatologist. The two discuss the progress of gout from its early stage to a more advanced stage, differences in management, and the importance of getting the disease under control early.
Key Takeaways:
- Advanced gout, also known as chronic gout, is characterized by increased frequency/duration of gout flares and tophi formations that deform joints and restrict mobility.
- Gout exists and advances in between flares; if left untreated, the disease will progress to a more advanced state.
- While treatment options, such as pegloticase and other pain management tools, exist for advanced gout, it’s better to get the disease under control early.
- Treatment efficacy should be closely monitored by medical professionals to ensure uric acid levels are treated to a target of 6.0 mg/dL.
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Kicking Gout in the Acid is sponsored by Sobi.
Podcast Transcript
Ian Ponitz
Hello, and welcome to Kicking Gout In The Acid, a podcast from the Gout Education Society. My name is Ian Ponitz, and I’m your host for this series. Kicking Gout In The Acid features conversations between Dr. Larry Edwards, chairman and CEO of the Gout Education Society, and experts on the disease.
Each episode will dive into important topics that you, the listener, should know about gout. The goal? To feel empowered to get gout under control. In this episode, Dr. Edwards will be joined by Dr. Herb Baraf, current Senior Clinical Advisor at the National Institute of Health, Clinical Professor at George Washington University, and former practicing rheumatologist. The goal of this episode is to discuss difficult-to-manage gout, commonly known as advanced or chronic gout. Advanced gout is a serious condition that requires specialized care and treatment. So we’ll spend today’s episode breaking it all down. Dr. Edwards, take it from here.
Dr. Larry Edwards
Thanks, Ian. I’m joined today by Dr. Herb Baraf, a member of the Gout Education Society’s International Advisory Council. He’s an internationally recognized expert in gout, and especially in the more difficult-to-treat forms of gout. Herb, can you give a little more description of who you are and what your tie to gout is?
Dr. Herbert Baraf
So I’m a clinical rheumatologist. I left private practice about two years ago after 40-plus years. I’m still a clinical professor of medicine at George Washington, and I’m involved in the teaching program of the Rheumatology Fellows at the National Institutes of Health. I’ve had an interest in gout since my fellowship, where, as a fellow, I was in charge of the Gout Clinic at the Duke-Durham VA’s Gout Clinic and became interested in that, and was always interested in teaching about gout. Then, in the early 2000s, having had a very active clinical trials program, we finally started getting involved in clinical trials with gout. And in that setting made a series of observations that took me from the private practice realm into a more national and international community of gout experts because of the observations that were made.
Dr. Larry Edwards
Yeah, we’ll talk a little bit about that aspect of gout treatment a little later on here. The topic of the podcast today is really looking at the natural progression of gout when it’s untreated or undertreated, and how we end up, if untreated, with a very bad, crippling form of arthritis.
In the second part of our podcast, we’ll go and look at how the approach to treating difficult-to-manage gout and advanced gout differs from early phases of the disease, and we really want your input a lot on that.
So let me ask you, Herb, if you could just kind of visualize for the listening audience here what the early stages of gout would look like in the gout clinic at the VA when you would see them there.
Dr. Herbert Baraf
Well, you know, I look at gout, and I think it’s useful for individuals with gout to understand it this way. I look at gout as basically two diseases. What comes to the gout patient’s consciousness initially is this acute, horrific pain, swelling, redness, often in the forefoot or the midfoot or the ankle, that leads to a trip to the emergency room or a middle-of-the-night phone call to the doctor to relieve the pain. And that’s caused by an acute arthritis in that particular joint, usually a single joint with a first attack.
But in truth, gout is two diseases. The first disease is actually a disease of the body’s metabolism, where one has difficulty in eliminating uric acid through the kidneys and through the digestive tract, and so it builds up. And uric acid is a chemical that, at a certain point, begins to crystallize in the serum, and those crystals deposit very gradually onto the joints.
And over time, the accumulation of those crystals from this metabolic disease, this persistent elevation of uric acid, begins to cause problems. And the problems are the attack of gout. So the first disease is a metabolic disease, and patients are really not aware of that, and it’s going on, and it’s under the surface for several years to even decades. And then this explosive onset of the arthritis. Now, the arthritis itself initially is just an occasional flare-up of severe pain that lasts for a few days, responds to simple medication, and gets better. But over time, these flare-ups occur more frequently, and multiple joints become affected. The mistake that most physicians fall into is thinking that by controlling the attack of gout, controlling the arthritis is sufficient in managing the patient. Whereas in truth, if you don’t fix the other disease, the metabolic disease, lower the uric acid to keep it from precipitating in the joints, gout will progress.
I think that’s a simplistic but reasonable way to talk about this journey. So if you can picture you as the patient showing up in an emergency room with a swollen great toe that awakens you in the middle of the night, and you go into, if you’re old enough to remember the Wayback Machine from Rocky and Bullwinkle, go back five years, and instead of going to the emergency room, have someone open your toe up in the operating room and look at it. Never had any problems with it, no pain, but you’re just sort of, in theory, looking at it. What does it look like? And what it looks like on the inside is that there is a caking of crystalline matter on the surface of the joint that hasn’t come to anyone’s attention until another five years going forward, coming back to the future, if you will. So this thing percolates the metabolic disease, the crystal deposits, over a long period of time until something happens that triggers the first attack. So two diseases, a metabolic disease and an arthritis.
Dr. Larry Edwards
Yeah, I think that’s a very important aspect of gout that certainly a large number of patients and a lot of physicians think that when the patient is symptomatic, they have gout and when they don’t have symptoms, they don’t have gout any longer, when in fact this process that you described very eloquently is going on all the time and causes a chronic inflammatory process that’s really the trigger for a lot of the other comorbid diseases that are associated with gout, like heart disease and strokes and kidney disease, etc. So, yeah, I think that’s an excellent point, that this is what we call intercritical phases of gout, so the time between the flares is very important, unrecognized by the patients, and part of the reason why the disease is undertreated.
So we’re in a phase after the first attack where these attacks occur once or twice a year, and if untreated, over time, over many years or a decade, they’ll stop being normal-feeling periods between the attacks and start slowly escalating to where there’s always pain there, and there’s swelling there. And we call this the advanced phase. Can you describe a little bit what that looks like?
Dr. Herbert Baraf
Over time, as these crystals accumulate above and beyond the attack, the second attack a year later, the third attack six months after that, the fourth attack six weeks after that, and then the ongoing pain, swelling, soreness, and stiffness in joints, you begin to form, not just in the joints, but in the soft tissues, lumps. And these lumps, these palpable physical lumps or nodules called tophi begin to erupt. And these can become, in some individuals, quite severe.
By the way, the attacks don’t always occur in the feet. They occur in the hands. They occur in the wrists. It’s not always one joint. It can be multiple joints. Sometimes the attacks are so severe they’re accompanied by high fever. And this is all the worse, the more profound the deposits are, the worse the joint complaints occur. And the frustrating thing about it all, for those who suffer it, is that the whole thing’s avoidable. The whole thing’s manageable by just simply lowering the serum uric acid.
Dr. Larry Edwards
I think those are excellent points, Herb. I think you and I would both agree that, for the most part, treating gout in its earliest stages in the first year or two of symptoms, we can get almost everybody to the target that we want to, that we can calm things down within a year or so of treatment. As long as patients stay on therapy, they’re good to go. But all too many patients never get touched early on with uric acid-lowering therapies, and they just settle for treating the pain when it occasionally comes on. And then it gets to a stage where it’s a very difficult disease to treat.
Can you just go and kind of touch on both of those aspects, what we do early on for the treatment of gout as far as uric acid-lowering therapy and the medications we use, and then a little bit about the pain early on?
Dr. Herbert Baraf
So what medicines do we use? allopurinol and febuxostat are very effective in interfering with the production of uric acid. Where does uric acid come from? It comes from, for the most part, the breakdown of your own body’s cells. You’re constantly making new cells and breaking down old cells. And it occurs at a fairly steady rate, for the most part. Sometimes medicines interfere with excretion, and so you get high blood levels because you can’t excrete them. Or genetically, your kidney doesn’t have the proper apparatus to excrete it effectively, and that’s another source. Sometimes you have accelerated tissue breakdown for a variety of different reasons, some of which are genetic. However, this uric acid level is elevated. Getting it down with medicines that inhibit its production or enhance its excretion can be really quite effective.
So I mentioned allopurinol and febuxostat, and probenecid was actually the first gout medicine that was used to lower the serum uric acid level, and it’s been around for over 70 years. So this is a very controllable disease. I think the other point, and you touched on it, but the doctor may give you the drug, but then doesn’t check that it worked well. So, you know, if you’re on a cholesterol-lowering drug, you want to get the LDL cholesterol below 100. But if you’ve had a heart attack, you want to get it below 70.
Giving the right drug in the wrong dose and not achieving a target is useless in that situation. If you have high blood pressure and you’re given a blood pressure medicine, but no one checks your blood pressure again, you’re sort of out in the wilderness, and you don’t know if it’s working. And why would you treat blood pressure to decrease the risk of heart disease? Why would you treat high cholesterol to decrease the risk of cardiovascular disease or heart attack? So there are consequences to giving the right drug, but not monitoring it correctly.
If you took tests in high school or college, or professional school, and you had matching columns, you’ve got the right association of the disease and the drug, but it’s not whether you’re on the right drug; it’s whether you’re on the right drug at the right dose. And so the doctor has to play a role. And you’ve got to sometimes hold the doctor’s feet to the coals. You’ve got to say, Hey, I know you’ve got me on this drug, but how do we know if it’s working or not? And be very cognizant of what your blood uric acid level is. You want to get it below six. And in more severe cases, you want to get it below five.
Dr. Larry Edwards
I think that’s an important part of both this whole treatment is the patient’s role in their own care, and I think knowing your number, knowing your uric acid level is a very important thing that, as you say, you’re not going to make much headway, you’re not going to make any headway, in treating the clinical symptoms of gout over time unless you really abide by this treat-to-target approach. So I think that’s right.
Dr. Herbert Baraf
By the way, you and I could switch roles. Because not only do we agree, but we’ve dealt with the same reality.
Dr. Larry Edwards
Exactly. Well, I think we’ve all seen this. The thing with uric acid-lowering therapies is that, as you mentioned, there are some of them, like allopurinol and febuxostat, that block the formation of uric acid. There’s another type of them that enhances the kidney’s ability to excrete uric acid. We call those uricosurics.
There is another type of drug, and this is the one that you were involved in bringing into the limelight, and that’s one that actually breaks up uric acid molecules, and that’s an easily eliminated compound once that happens. So, that’s something that we think about predominantly with people with some form of advanced disease or somebody who just can’t respond or take the allopurinol and febuxostat.
Can you describe the step between treating kind of normal gout, and then do patients get referred to a rheumatologist, then for this more recent drug?
Dr. Herbert Baraf
Sure, I would hope so. When these crystalline deposits become so severe as to form lumps in the tissues, fingers, toes, elbows, knees, actually can even occur in the internal organs, then you need to take the bull by the horns. And I was fortunate enough to be invited to, I think you were in this trial also, the first phase-two trials with what we called at the time Puricase. So I was lucky enough to be involved in the first studies of an intravenous drug, the generic name is pegloticase. It is a uric acid-destroying molecule. So what does that mean?
The fact is that man and some of the great apes are the only living things that I’m aware of that don’t have this enzyme, uricase. And what does uricase do? It turns uric acid into something else. So it destroys it, it breaks it up. And with something else, it turns it into something else called allantoin. It’s very easily excreted by the kidneys. It doesn’t precipitate. It’s very, very soluble.
What we saw with the first patient that I treated, who had lumps on his hands, is that at 12 weeks, they were gone. Something that none of us had seen occur in anything less than five years. So we got this very accelerated, maybe 20 times what you would expect with oral treatment, very accelerated response. Some of these patients had not just lumps, but the lumps were broken out, and they were oozing. They couldn’t get their shoes on because of lumps on their feet and toes. And at 12 weeks, gone.
One of our colleagues in Ohio describes this drug as being Drano for the joints, just breaks everything up and makes it go away, and it’s rather remarkable. And for patients who are so severely afflicted with gout, not just the attacks, but also these unsightly lumps that interfere with ordinary function, they’re better, and their lives have changed.
Dr. Larry Edwards
Ya, I think, Herb, this is a good example that on our treat-to-target, the target that got set by most guidelines around the world is 6.0 mg/dL. That’s kind of a minimal target that we now know because of these studies of pegloticase that if you really, really, really lower the uric acid level, this resorption this reversal of the years and decades of uric acid accumulating can be treated much more rapidly than if you’re just sitting at 6.0, if you get it down to less than 1.0 or undetectable like you say.
So I think the whole approach to how we treat more aggressively with any form of uric acid-lowering therapy really kind of hinged on these studies. We’ve talked about uric acid-lowering for these people who have chronic pain because of the tophi present, because of the joint destruction that has occurred, and because of the chronic inflammation. How different is their pain management?
Dr. Herbert Baraf
One of the paradoxical things that goes against what your intuition would tell you is that when you start to lower your uric acid, actually, the risk of having an acute attack or a flare-up in your arthritis increases. And so when you begin to lower a patient’s uric acid, when your uric acid begins to fall, you might have more attacks. And we know this. I used to say to my patients that doesn’t mean I’m a bad doctor. This is actually a sign of improvement, and we prepare for it.
Typically, we’ll use colchicine, which is an ancient drug that inhibits inflammation caused by these crystals, and we’ll use it for a period of time. I usually, when starting allopurinol or febuxostat or pegloticase, will start the patient on it and will keep it going on a daily basis for at least six months or six months since the last attack, whichever that was. If the last attack was yesterday and you’ve been on it for five-and-a-half months, and you’re my patient, you’ve just earned another six months of treatment.
The goal is to control your pain and get this stuff out of your system. So realistically, that comes with a price of an increased risk of flare-ups, and you’ve got to get that under control as well. Now, colchicine isn’t the only drug we use. We use ibuprofen. We use naproxen, Celecoxib, standard anti-inflammatory drugs. Sometimes you need steroids, and for the most severe flare-ups, if those things don’t work, sometimes injecting the joint with a steroid or giving a high dose of steroid by mouth, and then tapering it over a few days, we’ll get it under control. In the rarest circumstance, there are a couple of drugs, one is on-label, one is not on-label, that are called IL-1 inhibitors. They are very effective, particularly in the most refractory, most difficult-to-manage flare-ups of gout.
Dr. Larry Edwards
I think that we do as physicians, kind of weigh our therapeutic approach to just how advanced the gout stages are in the patient. I think that we’ve given a pretty good overview of how one patient with gout progresses from the very earliest stages to these advanced stages that you’ve described. Our therapies get adjusted as we go along, from fairly easy management of a painful situation, and if we do it correctly and lower the uric acid, there are relatively few of those flares, and as long as the patient stays on therapy, they can essentially be cured of this disease.
I think the important part is that treating gout early, and being aggressive enough to get it under control, and then to maintain that over the years and decades, is the right way to do it.
Dr. Herbert Baraf
It’s a life-long commitment. You know, if you say, I’ve had this for five years, I haven’t had an attack, I’m feeling great, so I’m gonna stop it. What do I need to take these pills for? Then in three years, it’ll come roaring back.
I think the hardest thing about controlling gout, and I say this facetiously, is, my wife reminds me, men don’t follow directions well. And most people with gout, about 80, 90% of patients with gout, are male. I might also add that gout is very unusual prior to the age of 25 and pretty common after the age of 60. It’s very unusual in young women. I can think of only two young women I treated for proven gout. You know, you can prove gout by finding crystals in the joint, pulling them out, and looking at them under the microscope. But once a woman reaches the menopause, the incidence of gout, the risk for gout begin to parallel that of males. So the onset or incidence of gout becomes very similar to what it is in males after the age of 50 or 60.
It’s not a pediatric disease; it’s an adult disease. And as adults, we have to act as adults and take our medicine. Eat the spinach, as it were.
Dr. Larry Edwards
So we have good treatments for both the early stages and the late stages of gout. The important thing is to get on therapy and make sure your uric acid levels are suppressed. In today’s discussion, I think we’ve showcased that this is a progressive disease if it’s not treated well. It’s not something that should be put off and wait another year or two before I start uric acid-lowering therapy. This is the time to start it. The recommendations from the American College of Rheumatology are that everybody who’s had two attacks of gout should be on uric acid-lowering therapy. And if your uric acid at baseline is above 9.0, or you have chronic kidney disease or kidney stones, then all you need is one attack, and you should be placed on these uric acid-lowering therapies. I, and I’m sure you, fully agree with those indications for the disease.
I think we’ve pointed out that treating it early is so much easier than holding off and treating it as a well-established disease in you with lots of pain and destruction.
Herb, are there other topics that you’d like to mention here before we sign off from this podcast today?
Dr. Herbert Baraf
Interestingly, since leaving practice, I’ve had more time to read, so I just finished a biography of Benjamin Franklin. He was supposed to be in the Second Continental Congress and help work on the Constitution. He gave the job to Jefferson. They carried Franklin in. He was in a chair. They carried him by four people on rungs because he wanted to be there, but his gout was so horrible that he couldn’t walk into Constitution Hall.
Gout’s played a big role in history. Franklin had a number of flirtations in his life, and he wrote an essay to one of his lady friends called “Conversations with the Gout” because it often interfered with his amorous exploits. But he wrote this long conversation with the gout about how he should eat better and behave, and how he felt about dealing with the gout, with the accusations he made against this personification of the gout.
It’s played quite a role in history. There are many examples, both recently and two, three, four, five, six hundred years ago, that are rather eye-opening. The history and lore that surround gout are fascinating. So what I would say to you if you are out there with gout is that you are in good company. And just take care of yourself.
Dr. Larry Edwards
And more and more people are getting gout all the time. The incidence of it worldwide is steadily increasing. I’d like to thank you for coming in and shedding a lot of light on the problem of advanced gout and talking about how treatment changes over time. The historical vignettes, I think, are great.
We’re gonna hand it back to you, Ian.
Ian Ponitz
Thanks both for having this fruitful discussion today that can help those with gout, their caregivers, and medical professionals alike kick gout in the acid. If you have gout or treat gout, you can learn more through the website: gouteducation.org
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We’ll be back next month with another episode of Kicking Gout In The Acid. Until then, make sure to like, subscribe, and follow our shows on Apple Podcasts, Spotify, and other major platforms.
Thanks for listening in.
