Gout QD clinics - lessons from the Clinic QD307-QD311 Save

Hi there, and welcome to Gout QD Clinic. My name is Derek Mueller, PA from Saint Clair Shores, Michigan, and today's case is entitled senior year gout. So a 31 year old male presents for another opinion. This was a few years back regarding management of his known topaceous gout. So his first known flare of gout occurred at the age of 18, initially classic monoarthritis involving the toe joints with later involvement of his ankles and knees and ascension to his upper extremities throughout his late teens and early twenties, eventually developing gout in his elbows, his wrists, his MCP joints, his IP joints.

There wasn't many places where his gout was not by his early twenties. His medical history became complicated by depression, alcohol use disorder, obesity, deconditioning, chronic pain that, comes along with a gout of this severity. And the patient did not have any known inborn errors of uric acid metabolism such as Leishmanian syndrome and no underlying chronic kidney disease, at all. So this patient in his late teens and early twenties had consulted with several local rheumatologists as well as two major university centers. His past treatment included monotherapy of various urate lowering agents, including allopurinol, febuxostat, and Provenacid.

And for FLAIR treatment and prophylaxis, he was previously prescribed prednisone and colchicine, and he underwent surgical excision due to severity of several tophi on his body, involving his elbows, but these had recurred, with as time would pass with suboptimal management. He was at one point in time offered KRYSTEXXA in 2022 and also was co prescribed a low dose of methotrexate ten milligrams weekly. The patient only received about three infusions, and there was a question of a possible infusion reaction, which the patient described later on as, you know, may maybe the the IV line was infiltrated and his arm was just getting kinda itchy. So he eventually, this patient makes his way to to our our little clinic, for another opinion as he moved to our area of the state. On examination, this this young man has, again, at this point in his in his early thirties, has deformities and very bulky tophi of his feet, fist size draining tophi that are draining on his elbows, and innumerable tophi, upon his wrists, and fingers, and still having many severe flares and essentially requiring prednisone five to ten milligrams chronically.

So so at this point, we inherit a patient who's widely uncontrolled gout, tophaceous disease, chronic pain, multiple complex comorbidities. And the question is, how how are we gonna treat this guy? You know the list of what he's already been on. You know, you could say what has he not been on. And one of the patient's main questions is can he be retreated with KRYSTEXXA?

So I think this is a this is a very, difficult situation in in in that we know that an agent like, KRYSTEXXA or plugilodecase, is very effective for debulking agent and really a go to for a patient of this of this severity. However, there's this question of a of an of a possible infusion reaction. So I think retreatment really depends on the reason why the pegilodecase was initially discontinued. If it was a clear nonresponse, a rising serum uric acid after, after several levels of being very low or undetectable, or if a patient did have a verified infusion reaction that was serious or life threatening, I don't think we would even consider going back on pegyloticase therapy. But in this case, the patient had a questionable reaction history.

He received subtherapeutic probably or subefficacious dose of methotrexate prior. After hashing out the risks and benefits, we we decided to go for it. So methotrexate was initiated orally at about fifteen milligrams for about four weeks prior to his, retreatment pegilodecase, and he was also prescribed colchicine low dose zero point six milligrams daily for FLAIR prophylaxis. He received a total of three repeat, pegilodecase infusions. His baseline serum uric acid was 11.1 going down to 10.8, 10.5, and then later jumping back to 11.3.

So no, no no evidence of a reaction at any point in time, but but essentially at this point, we were calling the the uric therapy a failure. So you know what now? What's left to be done? So what would you do? I mean, in this situation, we think about combination therapy much like other rheumatic diseases.

Sometimes, one size does not fit all. This is a patient with severe refractory gout, so I think multiple mechanisms targeting the various pathways of of gout makes sense. So for him, we decided to combine xanthine oxidase inhibitor, allopurinol, as well as probenecid, uracosurc agent, and we targeted we titrated both agents, a combination of allopurinol six hundred milligrams as well as the probenecid to a thousand milligrams, twice a day through the course of, through the course of about five to six months. And what do you know? His uric acid goes from 5.7 to 5.6 over the last year, four point eight milligrams per deciliter, four point two, three point seven.

So he's had a very excellent response to combination oral therapy. So don't don't count out the old drugs. This patient is doing extraordinarily well. His Tophi are resolving. His flares are under much better control, and he's a happy guy at this point.

My key takeaways here, I mean this is a guy who's had very aggressive gout since his late teens with no underlying Sometimes we might go searching for an underlying etiology, but in this case none found. His comorbidities, and including him being a young guy with maybe questionable follow-up complicates the care. So we have to keep that in mind that these are sometimes people who have very busy lives and we have to try to work around that. It's also key that we know that pegilodecase, is sometimes our last ditch option. So we have to optimize that treatment as much as possible and the current evidence really, does point to stressing the importance of immunomodulation and improving, the odds of a positive outcome and long term treatment response with these patients.

So a respectable dose of methotrexate fifteen milligrams, weekly at least a month before is key. And then if all else fails, consider combination therapy of several tried and true agents to, achieve optimal urate lowering effect. Yeah. Very tough case, but thankfully, good outcome. So, so that's my case, and thank you for listening.

Be sure to tune in to rheumnow.com all July long for more gout content just like this.

Hey, everyone. My name is Brian Jaros. I am one of the rheumatologists at Northwestern University in Chicago, and today I'll be talking about a gout case that's a little bit bread and butter, but I think has some really important learning pearls that I wanted to discuss with you all. So this is a 71 year old male. He has a past medical history of high blood pressure, a remote history of MSSA bacteremia which ended up causing necrotizing glomerulone phritis.

A longstanding history of untreated gout at an outside hospital or institution, but presented to our hospital for three days of worsening joint pain. Was in his usual state of health when he developed very quick onset pain and swelling in his right ankle, similar to what he associated with prior gout flares but without a particular trigger. On exam, he was actually found to be febrile to 102 degrees Fahrenheit. His other vitals were normal, but he had an appreciable tophis over his left elbow as well as over the right patellar tendon kind of confirming the suspicion for longstanding gout. He had moderate warmth, tenderness, swelling of the right ankle that he was complaining about, but also actually of the right wrist and the right elbow.

And his labs showed a uric acid of 10, a very elevated CRP to 95 and ESR of 42. So although the suspicion was high for gout given the fevers, his history of bacteremia, he did undergo arthrocentesis of the right ankle which showed a massive number of white blood cells, 120,000. It did confirm gout crystals and cultures of that synovial fluid but also of the blood were negative at forty eight hours. So ultimately he was treated with colchicine and a prednisone taper with good success. When we were considering to initiate allopurinol, we obtained additional history from him that he was actually of Han Chinese ancestry.

And so initiation of allopurinol was deferred in favor of testing for HLA B5801. Two weeks later, this came back as positive. So that's one of the things I wanted to talk about today and take kind of a step back to talk about HLA B5801. I'll call it B58 for the purposes of this video so you don't have to keep listening to me say the full name. But refreshing ourselves on what HLA even is.

HLA stands for human leukocyte antigen and refers to a complex gene family that encodes proteins that are on most of our cell surfaces and they help our immune system distinguish between our own body and foreign invaders, so kind of a mechanism to help regulate against autoimmunity. There's three major genes, HLA A, B and C, and they contain different alleles or arrangements that are referred to by like a numbering system. And so most of us in rheumatology are probably familiar, for example, with HLA B27. These specific alleles then can confer individual risk for certain conditions, certain autoimmune disease, or even drug hypersensitivity. And so why is B5801 relevant to gout?

Well, this allele is actually associated with an increased risk of hypersensitivity reaction to allopurinol.

This is

one of the more potential serious adverse events of allopurinol use. So a 2025 meta analysis by Pham et al, looked at over thirteen thousand patients from 24 case control studies and found that carrying the HLA B5801 allele was associated with a massively increased risk of severe cutaneous reactions to allopurinol with an odds ratio of one hundred and seventeen point six compared to people without the allele. So, obviously, this is a really, really major risk factor. And it's relevant to us and our patients because these cutaneous reactions are more than just a little rash. They can really develop into serious manifestations, things like Stevens Johnson syndrome, TEN, DRESS, which as many of you know carries significant morbidity and actually even mortality.

The allele is more frequent in certain ancestral populations. So, specifically, those of Southeast Asian descent populations, like Han Chinese, Korean, Thai, Filipino, as well as people of African descent. And so as a result, the ACR 2020 clinical practice guidelines for gout actually conditionally recommend testing for this allele in at risk people of Southeast Asian descent and African American patients prior to starting allopurinol. They determined that testing in these at risk populations is probably a cost effective strategy, but actually conditionally recommend against universal testing in all populations, probably due to a lower prevalence of the allele and then an unclear cost benefit. So in our patient, we found this allele, we know he's at higher risk for allopurinol cutaneous reactions.

So how do we proceed? Clearly he needs long term treatment for tophaceous gouts. And the consideration here is febuxostat. So febuxostat is a non purine xanthine oxidase inhibitor, similar but not identical in mechanism to allopurinol, and is effective to reduce uric acid levels and gout. The typical starting dose is around forty milligrams and you

can

uptitrate this to the FDA dose of eighty milligrams, but some countries use all the way up to one hundred and twenty milligrams daily. So the question would be if this works like allopurinol and is effective, why is this also not a first line option that we typically use for gout? And the answer is there's a concern about additive cardiovascular risk with use of febuxostat. So in early trials of febuxostat, there was maybe a modest signal of a higher rate of cardiovascular events compared to allopurinol use in gout patients. And so the FDA actually mandated a post marketing study of febuxostat, which came out in 2018 and that was called the CARE study.

And this sought to examine whether febuxostat was non inferior to allopurinol with regards to MACE safety and gout. It was a massive study, over six thousand patients with gout and with a history of cardiovascular disease were randomized to either febuxostat or allopurinol with the primary endpoint being a composite of MACE essentially. And in brief summary, the median follow-up was thirty two months and febuxostat actually was non inferior to allopurinol with regards to the primary composite MACE endpoint. However, when they broke that composite into individual components, febuxostat actually demonstrated a higher rate of cardiovascular death, so four point three percent in the febuxostat group versus three point two percent in the allopurinol group. And then this drove a higher all cause mortality compared to allopurinol.

So as a result, an additional black box warning was added by the FDA for febuxostat for overall mortality in addition to cardiovascular risk and emphasized judicious use in select populations really when allopurinol could not be used. Some context and important things to note about the trial and criticisms would be that there was a very, very high rate of discontinuation of drug over fifty percent of people and also a large number were lost to follow-up around forty five percent. It's also worth noting that while the patients had a history of cardiovascular disease, so we're a high risk population, many of the patients were still not on risk optimizing medications, for example, like lipid lowering treatment. And mechanistically, it really remained unclear why febuxostat specifically would increase cardiovascular death compared to allopurinol. So do we have other data replicates this finding?

The answer is we have other data but actually challenges this finding. So in 2020, a European group published the FAST trial, which was prospective and randomized. It was open label, but blinded to the endpoint and non inferiority. I won't go for time sake into the whole ins and outs of this study, but it's worth noting that these were patients with cardiovascular risk factors but not necessarily disease, so a little bit of a lower risk population compared to CARES. It was similarly a huge study with over 6,000 patients, a long follow-up median treatment of three point six years.

And in their study, febuxostat was non inferior both for the primary composite endpoint, but also showed no increased cardiovascular death or all cause mortality, which was a difference compared to the finding in CARES. And notably in PHAST, there was a much, much lower follow-up loss to follow-up rate, so only about five point eight percent of patients were lost to follow-up. Also, I'll mention systemic meta analysis in 2021 by Gao et al also found no difference between febuxostat and valapurinol in terms of cardiovascular mortality. So at this point, are a little bit left to kind of make determinations, you know, whether febuxostat really carries this increased cardiovascular risk or not. My current practice is to follow the FDA guidelines to limit febuxostat use to those who are intolerant or who fail allopurinol and I will use it cautiously in patients who have a CV history with a lot of effort to control any risk factors that are modifiable.

I would also point out that we know we have emerging data that pretty solidly suggests that gout flares themselves are a risk factor for cardiovascular events. So ultimately, we need to get adequate control in these people regardless of the agent and if they can't take allopurinol then I think febuxostat really remains a viable option. And so in our patient, he was started on febuxostat forty milligrams, ultimately uptitrated to eighty milligrams daily and now with a serum uric acid of 4.1, which is below our goal of five for tophaceous gout and he's doing well, without further flares. So I hope this was, an interesting case, a little bit of a review of HLA B5801 and the risk for allopurinol hypersensitivity and also of febuxostat dosing, safety considerations, when to use it and what precautions we might take. Thanks for listening and take care everybody.

Hello everyone. Welcome to Gout QD Clinics. I'm Doctor. Richard Conway from Dublin, Ireland, and I'm going to present to you a case today called cellulitis and paradoxes. So this is the case of a man I was asked to see on the Rheumatology Consult Service.

He was 40 years old. He was a healthy, young man, normal body weight, no other real medical problems. And he had come into the hospital for the second time within a month with cellulitis. And this is odd, right? So you don't get cellulitis multiple times as a young person without something causing it, some immune deficiency or diabetes or something.

He didn't have any of these things. So I went up to see this man and I walked in to see him and had a look at this cellulitis in his leg, and my immediate reaction was, this is gout. This clearly is gout. Joints are swollen, they're red. There is cellulitis there.

And remember, cellulitis is inflammation of the skin. So while the commonest causes infection, other things, including crystal arthritis, can cause cellulitis. And I talked to this guy some more about his first episode. He said it was very similar to this, his right mid foot and his ankle, and then extending up his leg. And they'd given him intravenous antibiotics for a couple of weeks, went away about a week into the treatment, and then he went home and was okay.

And then he had a sudden recurrence of this again, came back in, was on intravenous antibiotics again. So obviously his primary team had had some inkling that this was a bit strange. They were asking a rheumatologist to come and see him. They thought there might be something rheumatic going on here. They'd even thought it might be gout.

So they had sent a serum urate on him, and this had come back at three twenty micromoles a liter, which is five point four milligrams a deciliter. And so they said, can't be gout, this is a normal urate, which indeed it is. It's below the crystallization point. So their reaction was, Yeah, can't be gout, we'll ask rheumatology if there's something else going on. And my reaction on seeing this was, But this is gout.

It's clearly what it is clinically. We should treat it as that, which is what we did with some steroids and he got better. So then the question is, why is his serum urate normal and why does he have gout? So his serum urate, you would think is normal as can happen during an acute flare. You get this paradoxical drop in the urate.

And I'm not sure we really know why that happens, but it does. It's quite a frequent thing and it can be very pronounced. So this guy has potentially dropped a bit into the normal range, but I've certainly seen patients where it drops down to two or three milligrams a deciliter from very high values. That can be a very pronounced paradoxical drop. We went and I had a kind of deeper chat to him about gout and this.

And he told me that he had once been diagnosed with gout. He had an episode of podagra about four or five years before this. So I looked back, saw what his, thankfully, a urate on at that time, with his primary care physician, and that urate was four thirty six micromoles a liter, which is seven point three milligrams a deciliter. So that fits okay. So we have him, he has what appears to be gout, he's on steroids, he's getting better.

I brought him back to my clinic and said, let's check your serum urate again. And this time it was three sixty two micromoles a liter, which is six point one milligrams a deciliter. So that's just about good enough for gout. It's odd to get gout at that level, but just about good enough. So I said, look, it's above the threshold.

You have gout clearly clinically. We're gonna start you on some allopurinol, one hundred milligrams, bit of colchicine. We'll bring you back in four to six weeks and recheck this uroagency where we've gotten to. So that's what we did. He came back to me, said he'd been fine, no more flare ups on the colchicine.

He'd kind of felt a little tingly, kind of maybe an impending flare at times, but seemed like the colchicine was suppressing it. Again, and we're supportive if needed it, that this is gout. We rechecked his urate, so he's on the allopurinol one hundred milligrams. I'm 100% sure this guy is taking it. His urate is now three seventy five micromoles a litre or six point three milligrams a decilitre.

So it's gone up despite being on allopurinol. So what's happening here? Possibilities, he not be taking the allopurinol. I don't think that's happening, so I have confidence in him. The allopurinol might not be working.

I don't think that's really a thing. It might not work well enough, but it certainly shouldn't be going the other way. So 100% I believe what was happening here is that we're seeing kind of a sustained paradoxical response that actually the urate is still rising back to its actual level. And so we are seeing an effect of the allopurinol. It would be higher if he wasn't on allopurinol.

It's just confusing because of the paradoxical drop at the time

of the

flare. So we increased his allopurinol two hundred milligrams and bring him back four to six weeks, and his urate has now dropped down again, but it's still around three sixty or six milligrams a deciliter. So increased the allopurinol again up to three hundred, bring them back in another six weeks. His urate is now back down to three twenty micromoles a litre, or five point four milligrams a decilitre. So I think we are seeing here the the proper effect of the allopurinol in suppressing the uric acid.

So we left him like that. He's now been another good few months. Haven't heard from him. He is due back in my clinic in a few months more time. I presume his gout is doing good and he's still taking his allopurinol and his colchicine.

So I've been Richard Conway and keep an eye on RheumNow for all the gout cutie clinics in this gout month.

Hello. Welcome to Gout QD clinics on RheumNow. Artie Cavanagh from San Diego. And my title is Lifestyle and Gout. That's the title I was originally came up with.

And then just as I was preparing for this, I thought maybe I would call it gout. Is it the journey or the destination? So it's a case. So it's a case of a gout patient that I have had for actually quite a while now. So this is Mr.

J. He is a very typical patient with gout, very strong family history, from The Philippines, had gout since the when he was in his thirties. Risk factors definitely included diet. He would always, very sheepishly tell me when he went to trips to The Philippines and the things he had eaten there, which he knew would set off his gout. The gout had been kind of a problem over some years.

When I first saw him, he was in his mid forties, and he was on a diuretic for heart failure. He had the dietary issues, as I said, a little bit of alcohol. Diet was an important one, family history, but also weight. So he was a good twenty five, 30. And so we talked about the reversible issues and the irreversible issues, and we had Mr.

J on allopurinol, and he had his the uric acid pretty close to goal. It was, at best, kind of in the high sixes, but he was having fairly frequent flares of gout. And by that, I mean, about every one or two months. And he knew the routine. We knew the routine.

We used nonsteroils. We used colchicine judiciously, kept

him

on his allopurinol, maximized the dose of that, use prednisone both orally and injectable as needed. And he did okay on this, except it was still not satisfying to either of us because he had the still the frequent episodes of gout. Then there was a hiatus of time. I didn't see him, and I figured he moved and went to another position. But then he came back after about four months, and he had lost somewhere between ten and fifteen pounds.

And I said, this is great. How did you do it? And he said, well, just eating sensibly and avoiding carbs and taking smaller portions and trying to avoid foods that I know will upset the gout. And the amazing part was that by this time now, he is not having flares of gout. So he still has gout.

He still had some tophi. Those were getting better. He's still on his medication. But I remember him very, very clearly and really used him as an example when I talked to other gout patients and told them that, listen, you're forty pounds overweight. You don't need to get to your high school weight.

You don't need to get to your fighting weight. If you lose a portion of your overweight, you were probably going to do much better using him as an example. And indeed, he did do very well, and I took that advice and tried to share it with patients. Of course, it was always very difficult. So then he was doing so well, like, we saw each other less frequently and then hadn't seen him for quite some time.

This is probably after about six, seven, eight years. See him again pretty recently, and he comes in now. And he's still doing well, and he's still doing good things diet wise that we had talked about, still maintained on his urate lowering therapy. But he brings in his son, and his son has had his first episode of gout in his late 20s. And his son is a good forty to fifty pounds overweight.

So, pretty soon, this being this day and age, we have the discussion of, what about those medications, the GLP-one receptor agonists? And what about using those for gout? And boy, this really got me thinking, and that's the subject of my gout QD clinics. The father did really great with lifestyle modification, which is very difficult and is achieved by only a small portion of patients, but he did really great by doing that. What about using the GLP-1s?

I think it's gout is maybe one of the most prominent conditions that we see for which these therapies could be really dramatically beneficial. But we've all had patients on the GLP-1s where the weight comes down, and it's miraculous, and the weight comes down, and then they stop, and the weight goes back up, and they're on that seesaw. And I got to thinking about this. Discussing with the father and his now my patient also, his son, I really wish that he would be able to do what his dad did and do it without the medications because I don't know what's going to happen. I know the GLP-1s may have other benefits and may be immune modulating and certainly have benefits across a number of diseases, not all of which are related to the weight loss.

But in this case, because they have seen people rebound, I wonder it's what would be better in the long run? Now, if you think of other chronic diseases, someone with high blood pressure, we don't tell them, well, gosh, lose weight and don't eat any salt, and your blood pressure would be lower, which it probably would. But we say, here, treat with these blood pressure lowering medications. The same thing with other types of approach to diabetes. We don't tell people that just do it naturally, and that's somehow better than the therapies that we have.

But I think it is pause when you think of some conditions for which people have had difficulty maintaining the lifestyle issues that have been healthy to them and proven healthy in larger populations. And so is it the journey, or is it the destination? I think maybe the journey might matter, and some journeys might be more successful than others. Although, as we're talking about weight, I think it is the destination. And getting there quick, getting a success is, I think, important for lots of patients.

So with gout, it's a condition I think we've known about for a very long time. I think we have great approaches to our patients. And now I think we have more ways to approach them, including lifestyle, but also some of the newer medications. So this is Arti Kavanaugh for the gout QD clinics for RheumNow.

Hello, welcome to another QD clinic for gout month brought to you by RheumNow. And I'm going to talk to you about when there's doubt in gout. This is a patient, a 63 year old patient with long standing diabetes on insulin for about the past fifteen years. He has been under really good control of diabetes. His a one c's have been right about six and hasn't had significant complications related to his diabetes.

He presented to an orthopedic physician with severe midfoot pain and diagnosed with Charcot arthropathy. Charcot foot is a diabetic neuroarthropathy. It's progressive. It's destructive. It's usually related to the neuropathy that's present in diabetes where you lose sensation, leading to a kind of repetitive, unrecognized trauma that causes inflammation, usually bone loss, eventually fractures, dislocation, subluxations, and and significant deformity, usually associated with diabetes, also attributable sometimes to things like alcohol or other forms of neuropathy.

It's usually warm, swollen erythematous. This was it's usually not painful despite the extensive damage that's there. He sees the orthopedic doctor, he's got midfoot destruction, he has a classic rocker bottom of the foot leading to this diagnosis. It is, however, moderately painful. It's not severely painful, the way we often think about for gout, but it's also not painless.

He's treated for the shark of the foot with immobilization in a boot, planned for surgical reconstruction, but he sees his endocrinologist, he says, I haven't really had significant issues with neuropathy. My diabetes has been under really good control, granted it has been a long standing disease. Is this really Charcot arthropathy? And so he gets some labs done. His uric acid comes out at ten.

And so he comes to see me with a question of, is this really Charcot, or could this be Gaudi arthropathy? And there's not necessarily one swollen joint or anything to aspirate, And so it's a little hard to say, could this be gouty erosive destruction from it? Again, not kind of that traditional pain. Again, maybe there's neuropathy that's also numbing that as well. So we go ahead and we do a a DEX scan, the dual energy CT scan, which highlighted that there was quite a bit of of monosodium urate crystals, the guided crystals present within his body, which is not a surprise when his uric acid is 10, but in particular, it highlighted that specifically on the midfoot there was extensive deposits that were there.

And so that really helped us indicate that this seems to be a gouty problem that we think is driving it. And so when you're not sure in gout, the teaching point, number one, is to think about using the dual energy CT scan. For him, it helped make the presumptive diagnosis that helped us get him started on urate lowering therapy. We got him under goal. His uric acid is now very well controlled.

He's had stabilization of his disease. He's had a surgical reconstruction of his foot, and there's been no signs of any progress of the disease either from the Charcot neuroarthropathy or from gout. But nut number two, seeing the Charcot arthropathy, which is something that we don't necessarily always see in rheumatology, but, having it under differential, that gout can sometimes mimic this. So interesting case for me that I learned a lot from and and a satisfying case when you make the diagnosis, you you see those, you know, those green deposits on that DEX scan, and you intervene with a treat to target approach. So I hope you appreciate this case.

Check-in with RheumNow for a lot more of QD clinics and other material for gout month.