Gout Lessons from the Clinic Part 2 Save

Hi, it's Doctor. Janet Pope. This is Acuity Clinic talking about gout. So this is entitled, Can Rheumatoid Arthritis and Gout Manifest Simultaneously? I hope you like this case.

And if you do, you can follow me as well at Janet Burdope on X. So this is a true case. 54 year old man with seropositive RA. In past, he was strongly seropositive and ACRA positive. He had nodular erosive rheumatoid arthritis onsetting when he was 22 years old.

He was stable on methotrexate and hydroxychloroquine for years, as back then we didn't have advanced therapies. However, we will fast forward. So he's 54. When he was 44, he lost his job. There was downsizing at his factory, and he became a bit depressed.

He said that he was getting more complaints recently of Achilles nodules and lumps on his toes. On exam, he had what appeared to be tophi over some MTPs and on his toes proximally, and his first MTP on one foot was slightly chronically swollen. He denied any pink or red joints and none were pink or red today. Other joints were all excellent. So it was a swollen joint count of one.

So being the detective, I asked what's been going on. So he's had this poor mood. He hasn't been working for ten years. So he said he admitted to drinking 10 to 12 beers a day for probably the last eight or ten years. He had a high uric acid left level when I ordered it, and we certainly gave a lot of counseling about methotrexate.

And he did admit to being fairly noncompliant with methotrexate because he had been in remission with RA for years. So the questions are, does he have RA? Is there a negative association between RA and gout? Or is it actually contrary to what we were taught way back when? Is it actually an increased association?

And is beer worse than other alcohol? So yes, he had RA for decades. I went back and confirmed his positive serology. I couldn't find old x rays, but we did new x rays that showed a classic area first MTP erosion. Old X rays were reported, but not viewable from years ago as having a small erosion at ulnar stylet in second MCP on the radial side, which would go with RA.

And RA was stable for years. So I'm concerned about his alcohol use and abuse and obviously his mood and the use of methotrexate. So is this gout? Yes. He's had a recent change in his status, heavy alcohol use, a very high uric acid.

He has TOFI and he's been a heavy drinker. His feet are involved and not other areas. So why would it be a beer causing worse problems? So beer is rich in purines. So consuming beer, we know conversing gout, so can other alcohol.

But there is data that basically alcohol from beer is worse for gout. And then it might be the yeast, it might be the amount of purine load and the fermentation. It's really hard to know. It's also the sugar content. So I did look it up.

Beer has the highest purine content and in wine and spirits, it's low. The impact on uric acid for beer is far stronger than wine or spirits. So we used to think that rheumatoid arthritis and gout did not coexist or existed rarely. Why? RA more common in women back in the day, it was women of childbearing years, so premenopausal.

Now our population is older and living longer. And also women back in the day drank less alcohol. And in general, we advise against some alcohol use or certainly any moderate alcohol use when people are taking methotrexate. So what's different now is women are often onsetting perimenopausal in our early rheumatoid arthritis or CATCH cohort. The mean age of onset is 55.

That's the same with The US cohort brass and it's fairly similar to in The UK and in France, it's early fifties. So it's a different age distribution. Our patients used to be mostly normal weight. Now the whole population has more metabolic syndrome. And two thirds of our patients with rheumatoid arthritis in many studies, including our early arthritis study, two thirds of our patients are overweight.

So one third obese, one third overweight, one third normal weight. The other thing is our patients are getting more comorbid as they live longer. Hypertension is increased in patients with RA. Probably two thirds of RA patients over time will develop hypertension. Our guidelines say use diuretics as first line.

There's more heart failure as they get older and more coronary artery disease. Starting aspirin might exacerbate gout and also if not in steady state going up and down on the doses. CKD is slightly increased in RA, but also increased if using NSAIDs and from the comorbidities. Also alcohol became fashionable in the baby boomers having their red wine, a drink a day. And it's going down again in usage, but that could increase gout.

The other thing is with metabolic syndrome, there's more SGLT2 use if they have concomitant type two diabetes. SGLT2 inhibitors act like allopurinol. They break down purines so you get more gout before you can get less gout over time. Also, maybe there's misclassification because we have more seronegative RA about thirty to forty percent in many early RA cohorts and it can present as pseudo RA. So what about the frequency of gout in RA?

So there are some studies, there's studies out of Korea, a population cohort, and they found that gout was almost threefold higher in RA than the general population age and sex match. Similar from Israel, it was about a double prevalence compared to non RA patients. So we have a large rheumatoid arthritis registry, the Ontario Best Practice Research Initiative or OBRI. So almost three thousand six hundred patients, a hundred and thirteen with gout plus RA. And how are they different, the gout plus RA patients?

They're more common in men. So women are overall about seventy nine percent, whereas it's only fifty two percent women in the gout group. They're older. The gout patients on average in a prevalent cohort were 66 years old. The other RA patients were 58 years old.

And not surprisingly, they had more metabolic type problems, cardiovascular disease, diabetes, hypertension, and they were one point eight times more likely to be obese. So what are the take home messages? Gout can coexist in RA. It's approximately three percent of our prevalent RA population. There's more of the traditional risk factors in those who have gout and there's a little bit more glucocorticoid use and those who have concomitant gout and that might be because they have two kinds of inflammatory arthritis instead of one and address the comorbidities.

But think of safe treatments if your patient with RA does have gout. I hope you enjoy watching our program on so many topics, including gout this month. Thank you.

Hello, and welcome to Gout QD Clinics with RheumNow. My name is Doctor. Rinalini Day and I'm based in London in The UK. And today's case that we'll be discussing is called gout, sepsis, or both. So I'd like to tell you about a gentleman whom I saw during an on call shift in rheumatology.

So, he was a 60 year old man who was admitted to hospital after an upper gastrointestinal bleed. And just before this, he had been newly diagnosed with chronic myeloid leukemia. He also had end stage kidney disease requiring hemodynamicsis. And early in his admission, he had been treated with almost two weeks of broad spectrum intravenous antibiotics for presumed sepsis of unknown source. So there's plenty of things going on, very, very complex.

Just as he was beginning to improve, the medical team became concerned about both of his knees. So they were swollen, particularly on the left hand side, and an ultrasound showed that there was bilateral knee effusions with synovitis. So, rheumatology was asked whether this was an inflammatory arthritis and whether aspiration or steroid injection might help. So as we can see, the picture is not really straightforward. When I went to see him, he told me he'd had knee pain on and off for years, but the swelling was new.

When I examined him, both of the knees were swollen but cool, with surprisingly good range of movement. It was unclear from the history if there had been any redness or warmth prior to this. Looking at his blood tests, his inflammatory markers were still quite high, although they were falling, and his white cell count continued to remain high, but of course, he'd just been diagnosed with CML, so the usefulness of this was limited. So would you assume this was gout? Would you continue treating as possible septic arthritis?

Or would you insist on aspirating the joint, which is, of course, the gold standard in these cases? Now, the difficulty was that both diagnoses were entirely plausible. It could have been a partially treated septic arthritis, or gout, or both. He had several strong risk factors for gout. So I've mentioned that he was dialysis dependent, he had a documented hyperuricemia, and had newly diagnosed leukemia with increased cell turnover.

So that's important to consider. But he also had every reason to make us worry about infections, specifically septic arthritis. So he'd recently been septic, he'd already received prolonged antibiotics, which could partially treat septic arthritis, and he remained systemically unwell. The obvious next step was joint aspiration. But unfortunately, on this occasion, and subsequently to me seeing him, he kept refusing.

He'd had a painful aspiration many years ago and was adamant he didn't want another one, despite a long discussion about why it would be so important, which left us with a genuine diagnostic dilemma. Management wasn't easy either. So normally, we have several options for treating a gout flare, as you'll be aware, but in his case, almost all of them were problematic. So his end stage kidney disease meant colchicine wasn't appropriate. His recent gastrointestinal bleed meant that non steroidal anti inflammatories and systemic steroids were unattractive options.

And without excluding infection, even an intra articular steroid injection wasn't really something we could confidently offer, in addition to the fact he was refusing the procedure. So, we continued antibiotics as planned by the treating team, encouraged him to reconsider the aspiration, and planned treatment around whatever additional diagnostic information we could obtain. So, what are the teaching points from this case? The first is probably the most important, and that is never let the diagnosis of gout stop you from thinking about septic arthritis. In fact, even if aspiration had shown the presence of monosodium urate crystals, it would of course still be prudent to check the Gram stain and cultures.

Crystal arthritis and septic arthritis can coexist. In fact, in around one in twenty people with crystal arthritis, septic arthritis is also present. And of course, finding crystals never excludes infection. Secondly, it's important to remember that risk factors don't always point in one direction. So, this gentleman had multiple reasons to develop GAPT, but equally, he had multiple reasons to develop septic arthritis.

And that's exactly the sort of person in whom aspiration becomes even more valuable. Finally, diagnosing gout is often easier than treating it. So, patients with advanced kidney disease, recent gastrointestinal bleeding, malignancy, or other multiple comorbidities frequently can't receive our standard therapies. So, choosing a safe treatment requires just as much thought as making the diagnosis. So, all in all, aspiration remains crucial in the diagnosis and management of the hot joint, including for gout.

The presence of crystals does not exclude infection. The final lesson from this case is that diagnosing gout is really only half the battle. Treating gout in medically complex patients often requires us to rethink our usual approach. This gentleman had dialysis dependent kidney failure, a recent gastrointestinal bleed, and a new diagnosis of CML. Nonsteroidal anti inflammatories were inappropriate, colchicine carried a high risk of toxicity in the context of renal failure, and prolonged high dose steroids were far from ideal in someone where infection remained on the differential and who was about to start treatment for a hematological malignancy.

In these situations, there often isn't a perfect option. The key is to balance efficacy against safety, involve the wider multidisciplinary team and individualise treatment rather than reaching automatically for what we would consider a standard regimen. Thank you for listening and do look out for more from the Gout QD clinics on RheumNow. Thank you.

Hi there and welcome to RheumNow Gout QD clinic. My name's Derek Mueller, PA from Saint Clair Shores, Michigan, and my case today is titled pegloidicase immunomodulation, what's on the menu? So patient I saw recently, a 64 year old black male with a past medical history of end stage renal disease secondary to hypertension and diabetes presented for management of uncontrolled gout. So this patient had typical episodes of acute gout for the last twenty years involving his MTP joints initially with progressive, ascension into his, his ankles, his knees, his wrists and elbows, throughout the subsequent years. The patient had a remote history of treatment with allopurinol, was previously treated with prednisone and colchicine as needed for flares.

At the initial visit when I saw this gentleman, he was on the combination of colchicine and probenecid, the colbenemid combination pill. It's five hundred milligrams of probenecid and zero point five milligrams of colchicine. He was on this medication daily by an outside center despite his current GFR being at 15. When I examined this man, he had marble sized tophi, all over the place involving his toes, ankles, elbows, and wrists. And he had reported for the past few years about three to four flares on average.

And his baseline serum uric acid at the time of the initial visit was 11.4. So very uncontrolled gout in this patient. And to throw a wrench in it too, the end stage renal disease, his nephrologist was also talking about starting dialysis in the very recent future. So there was already a surgery date for his fistula creation. So we deemed it necessary that this patient was a candidate for uricase therapy, and of course the addition of immunomodulation would be the best chance of success for this patient to control his gout and sustain a serum uric acid level of less than six.

So in this case, we're thinking what's the next best step, with his end stage renal disease and plan for dialysis. This may narrow our options for immunomodulation. So with that being said, let's go ahead and quickly review the options that we have on the table. It's certainly apparent that immunomodulation drastically increases the success of uricase therapy. Our biggest evidence basis for this is the with the use of methotrexate, specifically, the more recent MIRROR trial that included, a comparison of patients treated with pegilodecase plus fifteen milligrams of methotrexate weekly versus pegilodecase alone without methotrexate.

And again, the dose that was utilized in this trial was fifteen milligrams of methotrexate with a run-in of about four weeks prior to first infusion. And that was a trial of 152 patients. And the primary outcome was a six month responder rate. So serum uric acid of less than six, eighty percent of visits throughout six months. And that responder rate was seventy one percent in the methotrexate and peglodecase treatment arm versus, thirty nine percent on peglodecase alone.

One thing of note was that in the MIRROR trial, patients with an eGFR of less than 40 were excluded from the trial. However, some, analyses have shown in that trial that there were similar responder rates in those with mild CKD, so between, forty and sixty. In this case, methotrexate is really not an option for our patient with end stage renal disease and that plan for dialysis, given the significant risk of toxicity with methotrexate. That's a no go here. So what else is on the menu?

Mycophenolate mofetil. This is another potentially, useful option that we do have some data for to improve the success of uricase therapy. And this is based on a smaller trial, the ReCePI trial, and this was published back in 2021. So small trial of about 32 patients. One group treated with pegilodecase and MMF one thousand milligrams twice a day with a two week run-in prior to infusion number one, versus monotherapy with pegilodecase.

The endpoint was the persistent achievement of serum uric acid of less than six milligrams per deciliter at the twelve week point that was 80 6% achieved in the MMF arm versus 40% no MMF. And then at the twenty four week endpoint, this was sixty eight percent in the MMF arm and thirty percent in the pegylodecase alone. Other options, azathioprine, the data for this is, very weak, only small case studies suggest its efficacy as a immunomodulating agent. And then the last option on the menu here that I wanna bring attention to is leflutamide. There are also small case reports suggesting that this is an effective immunomodulator.

One of the key benefits of leflutamide as an immunomodulator, this is a medication that is not necessarily heavily renally metabolized. This medication also does have a very long half life, so the active metabolite of leflunomide has teraflunomide. This has an eighteen to nineteen day half life, so quite impressive. And I know that patient compliance is sometimes an issue. This is also a patient who's on a plethora of other drugs for controlling his diabetes and hypertension and manifestations of end stage renal disease.

So a single dose pill that if potentially missed a few doses could confer a very, substantial advantage if we're trying to maximize the effectiveness of uricase therapy. So some cons, there is some, concern that because leflutamide does have uricosuric properties, that this might that this may impact this monitoring of serum uric acid on pegylodecase treatment. We really don't know the magnitude of the uricosuric effect of leflunomide. This could potentially be mitigated by having a run-in period of leflunomide prior to treatment, seeing where that serum uric acid lies after a month of treatment so we have an understanding of the magnitude of that decrease, while we are monitoring patients moving forward. So in this case, the patient ended up, starting on hemodialysis.

And in the meantime, he was treated with, we had a plan to institute leflunomide as a immunomodulating agent. So we started leflunomide at twenty milligrams once a day. His serum uric acid was then checked a few weeks later. There was not a significant change in his serum uric acid. He then successfully went on to receive a total of 14 pegylodecase infusions

with

an undetectable serum uric acid, less than one point zero milligrams per deciliter at every pre every single infusion. And, essentially, his he had some mobilization flares from the get go as one would expect. These were, managed with intra articular steroids and at one point a single dose of canakinumab. This patient was deemed a success after fourteen infusions with no, well well con great control of his flares and the resolution of his of his toe fibre burden that he had. And the patient was later transitioned from this combination to allopurinol, which was titrated to a goal maintaining his serum uric acid of less than six.

So this was a big time success, maybe not a very conventional approach, but in this case, the importance was to maximize this therapy. And although methotrexate remains the most evidence based option, the patient's past medical history and comorbidities, were such that we needed to think outside the box. So yes, MMF does have the second largest basis of evidence for immunomodulation, but this patient had a very large pill burden and this, for compliance reasons, we, had considered another option, which in this case was leflunomide. Not as evidence based, but I think that there is mechanistic advantages, compliance advantages to using leflunomide, and this is something that our clinic does have more experience with and, hope hopefully something that can be replicated in formal formal trials moving forward. So that's my case.

Thank you so much for listening and tune in to roomnow.com for more gout content just like this.

Hello, everyone. Welcome to Gout QD Clinics. I am Doctor. Richard Conway from Dublin, Ireland, and I'm presenting a case to you today that I've titled Don't Presume on IL-one. So this is the case I was asked to see by one of my nephrology colleagues.

It is a man who is 64 years old. He has a history of gout and looking at him, he clearly has polyarticular, tulphaceous gout. He's tophi everywhere, complete mess. Now he's seeing nephrology, which would give a suggestion of why he has gout. So this guy has stage four chronic kidney disease.

He has a urate of five thirty three, which is high, so five thirty three micromoles a liter, which is probably around seven, seven point five milligrams a deciliter, and high enough to cause gout, not outrageously high, but we do see that some people with urates that actually aren't that high do get quite severe tofacious disease and there are genetic and other factors involved in that. So I think this guy in some ways is just unlucky. He has kind of an expected urate level for his level of chronic kidney disease, but it's affecting him quite severely. And as well as a tophi, he actually has severe disease in terms of his disease activity. So they've called me because he's constantly flaring.

Love my nephrology colleagues, they are very multi skilled, so they've been managing his gout. They've been treating this with steroids and some colchicine, which is great to see. This place has level of kidney disease. They've been happy to use that. And they're able to settle him with high doses of steroids and a bit of colchicine, but they can't get the steroids down, he keeps flaring up.

He was previously on allopurinol, but he had a severe cutaneous reaction to this, so that was stopped despite it being dosed appropriately cautiously by our nephrology colleagues. And he's then being commenced on febuxostat by then. So he's on eighty milligrams of febuxostat and they rang me asking, What do we do now? We can't settle this man's gout. The specific question was, Do we need to give him Rasburicase?

And my reaction to that was, well, maybe you could give him Rasburicase. He's lots of tophi. It'll help get rid of them, but it actually isn't going to help what his and your actual problem is, which is that he's flaring all over the place and you can't get his steroids down and his steroid side effects are accumulating rapidly. So it's not a terrible idea, but it's probably not the solution to the question that you are actually asking here. As yours has come down really nicely with the febuxostat, so it's down to two forty, which is a four milligrams a deciliter, so that's good enough.

We'd be happy with that. So what further complicating factor arose here is that this man, which always has multiple medical problems, is actually homeless. He's living in a hostel. He's not completely living on the streets, but he is homeless, which can complicate medication administration and other things. You'll always be a little bit concerned about adherence as well.

But I think we know from what urate his has done and how it's responded that he is actually taking his medication as he should. So we consider this again. We figured what are our options for actually controlling the flares of this disease? So yeah, the steroids work, but he's had too much of them. We can't keep doing this.

We can't really give him any more. Polchicine with his chronic kidney disease, we definitely can't give him NSAIDs with his chronic kidney disease. So the option we settled on was IL-one inhibitor. Now, where I work, we are unfortunate in this way in that we only have one IL-one inhibitor in the country, which is anakinra daily injection. We do not have canakinumab available, so anakinra is our only option here.

We did have fears about doing this. We've got a self injection medicine on a daily basis that you're giving to someone who is in homeless accommodation, that this maybe isn't going to work out well. There are going to be administration and logistical challenges here. But we talked to the man. He was happy to try it.

He thought he was going to be able to do it. So he said, let's give this a try. Let's start on a Kinra. So he started anakinra, brought him back to clinic a couple of weeks later and he's doing brilliantly. He's the best he has been in years.

He has no pain. He's doing his Anakinra successfully. He's had no injection site reactions or anything. He's happy. His steroids have come down to ten milligrams of prednisone from about thirty milligrams beforehand.

Make a plan to get them off further. Say we continue the anakinra for as long as it takes, because we don't want to be going back on steroids. We think until these tofae are gone, this guy is going to keep flaring. So, we have had him on anakinra now for a good number of months. He's done really well.

His steroids are gone. He's still on his febuxostat and he's happy out. He's still a stophy. We're still continuing the anakinra for as long as we need to. He's happy with that.

So I think the big lesson here in this case is, well, that you treat the actual problem in front of you. If the problem is the gout flares, you do not need more urate lowering therapy for somebody who is already at target and that we really shouldn't presume what patients can or can't do or will be willing to do without asking them. And this man, despite his challenging accommodation situation, he was actually very happy and willing and capable of doing these daily injections. So I'm Mr. Conway, and do check out RheumNow for all the activities over this Goutament.