What Lies Beneath - Uric Acid Deposition & Imaging Save

Hello everyone. Welcome to Tuesday night rheumatology. This episode of TNR is devoted to gout. Specifically, what lies beneath in gout? What's happening with urate?

How do we quantify it, how do we image it. This is going to be a really interesting session. I want to acknowledge the support of Sobe who's sponsoring or supporting the education about gout in this campaign month of July. We have a lot that's already up on the website and more coming your way. We'll be doing four Tuesday night rheumatology devoted to gout.

Tonight's session is again, devoted to uric acid deposition and imaging. I have a panel of experts here. I'm going to ask them to introduce themselves. I'm Jack Cush in Dallas, Texas. Doctor.

Dalbeth.

Hi, I'm Nicholas Elbeath, I'm a rheumatologist from Auckland, New Zealand.

And Doctor. Tedeschi.

Hi, I'm Sarah Tedeschi. I'm a rheumatologist at Brigham and Women's Hospital in Boston.

And Doctor. Fitzgerald.

Hi, I'm John Fitzgerald. I'm at UCLA and by my shirt also GLA, Greater Los Angeles Veterans Association. And I'm a self disclosed ultrasound enthusiast.

Excellent. All right, so we're going to go to, our presentations here for everyone to view. As I said, this program is, supported by Sobe. I want to remind you, the audience members, that you should ask your questions by clicking on the Q and A tab, and we'll address your questions throughout this webinar. So as you know, prior to these Tuesday night rheumatology sessions, we actually do surveys of rheumatologists.

With a one time email that went out Monday morning, we had 161 responses to eight questions coming from 25 countries, 60% of whom were from The United States. You can see from the respondents that 87 were rheumatologists, 6% were APPs and 4% were rheumatology fellows. We thank all of you for your input. When as you can see, we really have the expanse of experience being represented here with 40% in practice for thirty years, but 25% are really new to practice and 3% were fellows. I don't know why it's 3% over here and 4% over there, but it's close enough.

But a lot of you are young rheumatologists with 17% being in practice twenty to thirty years. We ask questions about diagnosis, about treatment, and about imaging and its role in gout. That's going to be the crux of our discussions in tonight's webinar. So we started out by asking this question, in what percentage of your new gout patients do you actually do arthrocetesis and crystal identification? You can see there's a real mix here.

When you see four quadrants of colors, that means there's no right answer, at least as far as the respondents go. I'm one of the people who were in orange, 27% who say, I don't do this anymore. I mean, I can do this. I don't have a microscope in my charity clinic where I do this, I'd have to send it off and ask for crystals and there are some issues there maybe, but the most popular answer is 29% saying about half my patients or more will I do Crystal ID. Twenty seven percent say, no, I'm not doing it.

Twenty five percent say, I do it in ten percent. Eighteen percent are doing it in about a quarter of their patients. Who wants to handle this? Why is the diagnosis of gout become very free form? Nicola?

Well, I'll talk about what I do. So I think I'm probably in about the ten to twenty five percent range. In my clinic, if there's a joint tap, that needs certainly if it needs injection, I'll aspirate it and I'll inject it in the clinic. And I'll if there's synovial fluid obtained, I'll send it to the lab. I don't do, arthrocentesis now or sorry, I don't do crystal identification in my clinic anymore.

I used to do that, but I think that in a busy rheumatology clinic, it just takes a lot of time and you really want to do it well and you want an accredited lab, you know, and actually have that properly documented. So, and sometimes there's also an issue about is there something else going on? Is there joint infection actually want a full synovial fluid analysis? So for all of those reasons, I would send the synovial fluid to the lab. I think there are situations where it is really useful.

And so I do certainly think that, if there is fluid to be tapped, it's it is worth tapping it if you're doing it in a in a clinical, you know, for a clinical indication. What I would say, though, is that I think for the vast majority of people with gout, gout is a clinical diagnosis. And we are physicians. We use our clinical method, history examination. And that ultimately is the core of how we diagnose most gout.

And of course, now we also have imaging, particularly ultrasound, which actually can often give us some really useful information if there's uncertainty. So I think certainly in my practice, I have moved much more to ultrasound. And I think that that is often really helpful, but I will certainly tap the joint, particularly if there's diagnostic uncertainty.

Sarah, what do you do?

My practice is pretty similar to Nicola's. And I also want to just take a step back and say that I think that where you practice may also, you know, this is going to affect what you do and what kind of patients are coming through your door. So for example, I mostly do research and I do not have very many clinic sessions. So it's rare for me to get somebody with a red hot joint walking into my clinic room. If I'm on the consult service in the hospital, that's a different situation.

But if it's a person coming to me because let's say their primary care doctor has referred them and they want advice, the chances are they're not coming in with a large effusion at the time that I'm seeing them. So like Nikola, if a person does come in with an effusion or if there's diagnostic uncertainty, that's when I go ahead and, aspirate the joint. Our microscope was actually just very recently removed from our clinic. And now we have one in the central lab in the hospital, but it takes time to walk over there. And so I often I'm sending the labs over to the hospital clinic.

Sometimes I'll go over if I have extra time after clinic ends, and I'll look at it myself, but the realities of the clinical practice are real. And I also use ultrasound at the bedside as part of my first line diagnostics for patients when there is this uncertainty.

So I don't know, maybe ten, fifteen years ago when the lab started throwing CLIA certification and why you can't do it in the clinic and whatever. We dealt with that in the rheumatology division and then the lab asked me to teach the lab about how to diagnose crystals on polarized microscopy. The guy who's not CLIA certified was teaching the CLIA, it was crazy. John, what do you do? Does

Yeah, so I Yeah, I'm going to echo a lot of what Nikola and Sarah said. I have certainly done less over the last twenty years than I would have before. And that's largely because of ultrasound. Ultrasound, you know, it has to do with certainty. You have a certainty before you do something diagnostic, whether it's ultrasound or an aspiration.

And, you know, if it's mid certainty, then even after an ultrasound, I'm, you know, I'll do an aspiration. If there's an indication for a corticosteroid injection, then I'm doing an aspiration. But I like ultrasound for patient education. So patients will be surprised to see that they've got crystals in joints that have never had a gout attack. They'll be surprised to see erosions, and there's a high prevalence of erosions at presentation.

I think higher when they're getting referred to the rheumatologist. So are the main indications. So I'm doing less, but it's still valuable. I had to fight to get rid of the term crystal confirmed gout. I really hated that term when we had used that in one of our clinics for ages because it's not required to make the diagnosis.

So,

John, do you get carried away with ultrasound because you're a self declared maven? So when you are doing this, do you do just the joint that's under attack or will you actually then survey other joints as well?

I survey other joints. The ultrasound has a few uses. One, it will help me with the diagnosis, but two, I really like it as patient education. Having the doctor tell the patient you need to do this, but when you show a patient the crystals and the amount of crystals in a joint and the erosions and crystals where there's never been an attack or it's between attacks and patients don't expect it and they see it, it really changes the way they perceive their disease. Patients don't like seeing erosions on their bone.

And I have to always remind them that, you know, the screen is this big, the joint is, you know, is much smaller. So, it's like, you know, cars appear larger than or smaller, whatever that saying is on the mirror. But it's think it's very diagnostic. I think it's motivating to patients. It's been a study I've wanted to do forever to have to randomize patients to an ultrasound group and see if they are more adherent.

Jack, can I just add, I really agree with John's comments about the value of ultrasound patient education? And I think often in those conversations where people aren't sure about urate lowering therapy, actually seeing their images is very motivating or can be very motivating. I just, just with respect to your question about which joints, I tend to scan affected joints and then I'll always scan the first MTP joints particularly. And particularly when you're looking for erosions or deposits even in people with very early disease it's that medial metatarsal head, first metatarsal head where you often do see that. So you really wanna get right around and have a good have a good look at that as well.

And obviously you can look at many other areas as well. And and you will see deposition at multiple sites you know the Achilles often the you know patella you know patella tendon you know double contour in the knee. But, you know, I think definitely, if you're short of time, you want to be looking at those first MTP joints. And the last thing I just say is that there's a really great EULA guidelines or recommendations around the use of imaging for crystal arthritis. And that guideline, I think, has some quite interesting and controversial sort of suggestions, particularly, indicating that they do feel that, that task force felt that ultrasound or dual energy CT could or advanced imaging could replace arthrocentesis and and synovial fluid analysis in in many clinical situations.

And there's also some great advice about which joints to scan as well for crystal arthritis.

Yeah. We might get into this later but at sometimes, you know, particularly if it's not Padagra, you clinically, you can't tell CPBD versus MSU is the is the culprit and so, that's that's a good indication and then, the other thing, first, I'd like just to thank Doctor. Cush for selecting gout to to give it some attention but I think the title imaging below or or I forgot the exact wording but yeah, the if that made me think of like an iceberg. That's what I think of as a TOFIS because you see so much more with the ultrasound. And there's a lot beneath what's apparent to patients.

And I think the ultrasound helps with that.

I use that exact analogy about an hour ago when my last patient I saw who's got a lot of tophi. Doctor. Fung in Waco, Texas makes the comment that time wise, it's about the same to do arthrocentesis and crystal ID as it is to do ultrasound. But ultrasound does give you these other benefits. You identify erosions, you identify other joints, but then there's the exactness of MSU versus CPPD crystals.

So I think for people in practice, is a bit of a time efficiency and cost efficiency in work. Sarah, so how do you negotiate that with your or how would you teach your fellows on that?

Well, I think there's also a really important patient satisfaction kind of, or sort of appeal to the patient component here where if a person's coming in and they're actually feeling relatively okay that day, they're not going to necessarily want you to put a needle into their joint. It's very different if you're saying you're really suffering, I'm gonna take out some fluid and inject some glucocorticoids in here. But if this is a walkie talkie person, I think an ultrasound is much simpler to do. And then you have that education component right there in their face, just as doctors Dahlia and Fitzgerald have mentioned. So for Fell, I'd say that another part of this actually is, again, depending on where you're practicing, the use of ultrasound in our particular rheumatology clinic is not as robust as I wish that it were.

And in Europe, muscular skeletal ultrasound is part of rheumatology fellowship basically in all of Europe and at least in our institution, and I think in a lot of places in The United States, is not. And so the availability of rheumatologists to do the ultrasound in real time during that visit is somewhat limited. I would encourage the fellows to go through ultrasound training, but not all of our fellows do that is the reality. So I would say for fellows who are listening, I think this is an excellent skill that's going to enhance your personal practice and your patient satisfaction and your own satisfaction as you go through the rest of your rheumatology practice.

I'd just also like to add that this is not just for fellows. Actually, as someone who did ultrasound training much later in my career and didn't learn as a fellow, actually, it's really something that even in mid career can really enhance your rheumatology practice and make it really interesting to learn a new skill in middle age rather than when you're young.

I will echo that. I was not an early adapter. It's a fairly quick learning curve.

And it's almost become, I think, an essential skill, especially for the diagnosis of crystal arthritis. It's really amazing. We'll get into that. Let's ask- Jack,

sorry, if I can just add, know, for the small joint, you can also then ultrasound guide the injection which which is less pain. You know, like I'm entertained how I used to and how a lot of people used to try and get into the MTP joint like we could fancifully somehow go between the two bones and and I don't know what we were trying to do sample cartilage or whatever but there's really a lot of little pouches of fluid that you can identify and then get after with ultrasound.

I've always used the house of God rule, which said something like a strong-arm and a 14 gauge needle can get almost any place. So we really want to avoid that. We asked the question about how do you quantify urate deposition on the right here? A patient with gout who has TOFI, a high serum urate, what would you do? Actually, can see in green and blue, they're saying, no, I don't quantify.

That in green, they're saying, I aim for because they have TOFI, a uric acid of under five. And in blue, they're saying, no, I just escalate my urate lowering therapy. And only four percent said that they would quantify with a deck scan. Now this needs to be juxtaposed to the next question on the left, which says, which imaging modality best quantifies total body urate, to face this volume? And then 88, 87% say it's decked.

So it's not like we have to convince people of its value, right? With a minority less than nine percent saying three d MSK ultrasound, nobody's doing MRI. So I guess the question is, do you need to do a quantification of total body urate or at least that there's tissue deposition besides the tip of the iceberg that you see? Do you need to do that by other modalities or just assume it's there and power through with aggressive therapies? John, how would you handle that?

So I love deck for research. It's a great way to quantify, crystal deposition. In most situations, I don't use deck clinically. It's less sensitive in the early years. It's less sensitive for liquid tophi.

It works well for solid tophi. I will use it when, for example, I'm not clear if a wrist pain is, you know, chronic and or critical gout or there's another etiology. So, I'll look to see in an area where I may not suspect it, or I'm not sure if it's CPP deposition versus MSU to try and figure that out because it's quite good at distinguishing your rate from calcium.

But will you use then if you're not going to rely so much on deck, will you use other modalities? Will ultrasound do enough for you to know that it's more than what I'm seeing on my physical exam and on my laboratory assessment?

Yeah, I mean, I think ultrasound is very good for MSU deposition, especially, you know, when it's clinically significant. We MSU deposition in asymptomatic hyperuricemia. There was that great study called Sons of Gout and you know, my dad has gout and the fellows were scanning my foot for a decade and I was slowly watching a double contour sign grow in front of me and you know, so it led to interesting questions.

Well, Sarah, how do you approach this issue of extent of disease? Is it purely clinical? Is it made better or worse by labs? And where does imaging fit in?

Yeah, so starting with the question here, do I try to even quantify? I typically do not try to pursue imaging of multiple joints. And I think that's what this implies here is if you're looking for sort of a total body volume, you're gonna need to image many, many joints. And with DECT, that's certainly possible for a patient, they're gonna be billed for that. That's a lot of CT scans that they're getting if we start taking that approach.

And I think for how would it potentially change my practice is ultimately the question. If somebody has visible TOFI, you're gonna treat until you see those TOFI go away or they hopefully stop having flares over time. There certainly could be subclinical TOFI that remain. And I think that I would be very curious to hear what Nicola thinks about this. This is really one of her areas of expertise, but I might say clinically, if they're still there and the person's not flaring, I might be okay with that.

So I don't think for me that the visualization of the burden is so important. I think the one aspect in which it can be informative for clinical care is when the patient is saying, my serum urate is less than six or it's less than five, and why am I still having these flares? And it's like, well, okay, because you actually still have it in your body. That's why. But I don't usually go ahead and get a deck to prove it to them.

But I'm curious. So, Nicola, can I turn it over to you and ask

So so I've I've I've done a lot of gout research using dual energy? You know, I think it's an amazing research tool. I think it's really helped us to understand patterns of deposition, the interaction between joint damage and MSU crystallization, what happens to the tophis over time with urate lowering therapy. So I think from a understanding disease and response to therapy in a research setting, it's really, it's an amazing tool. Like John and Sarah, I use it very infrequently in my clinical practice.

And I think whenever I'm ordering a test, I really need to be thinking how's this going to change my management? Is it going to alter my diagnosis or my management plan? And in reality, if I'm seeing people who have clinically evident TOFI, I know they have a very high MSU crystal burden. And I know that I'm going to want to treat that with intensive urate lowering therapy, get the serum urate below five milligrams per deciliter or, zero point three millimoles per liter. So, you know, it's not actually going to alter my management.

The, you know, I would maybe in my practice order a dual energy once or twice a year. I'm doing ultrasound for most of the patients I'm seeing in my clinic. So that I guess kind of shows you how infrequently I'm doing dual energy. And then the probably the couple of areas where I've done it recently where, I was just like, I think dual energy would be really useful here is first of all in that situation, Sarah said, where you've got someone who's actually had a low serum urate often for actually a long time, not just, you know, this year, but actually over a number of years and are still experiencing flares. Now in that situation, I'll often do an ultrasound first and if I see, you know, a double, you know, double contours or obviously a big tofus, I'm going to be saying, well, actually, you know, I'm happy.

I think we just need to keep going and continuing with the plan. Sometimes it's, you know, if they're having a lot of midfoot or sort of ankle, particularly midfoot, involvement, it's actually quite difficult to be sure, and you can get these little deposits which are present within the midfoot which you can't really see very well on ultrasound. And again in that situation that's a situation where actually I found dual energy really helpful. But again that's really, you know, one or two patients over the last few years. The other situation where I think it's really useful is where you have a patient who maybe presents with a nodule.

It's not, you know, it can't be needled for whatever reason. They've got hyperuricemia and you're thinking, is this a tofus or is this something else? And again, in that situation, a diagnostic perspective, I think it's really, it's very, very useful. Because if you see a whole lot of MSU on the dual energy, you're just like, yeah, this is great. But I wouldn't do a serial dual energies in that setting.

So, everyone's clearly indicated this is a research tool and there are exceptions to the rule where you might use it maybe a few times a year at the most. Many of the practitioners would say, this is not routinely available in my imaging centers that I have to refer to. They're not on-site, someone's got to go across town, whatever. How essential is it that the average practitioner have access to deck? I would say not at all, but I wanna know what you think.

I I guess what I'd say is that they may not be aware that their that their radiology provider has dual energy, but most of the CT systems now actually do have dual energy as part of their sort of routine system. So it may be just worth just that with their radiology provider because certainly, you know, most of the big vendors, their CT scanners will have dual energy capacity.

Yeah, the coronary artery calcium score is a dual energy scan. It's just, it's the same dual setting. So it's the same energy. It's getting the software that the companies charge for the add on. And I had a tough time getting our university to get it.

That was ten years ago probably, and we don't have it across the Street at the VA.

So John, you answered Doctor. Fung's question about the liquid TOFI. Do you want to tell the audience why you're using terms we know nothing about?

Yeah. Patients will sometimes express liquid TOFIS. It has also been called toothpaste. The other term that is a horrible term, and I would recommend never using it in front of a patient, is gout milk. But the dual energy CT can't see the suspended crystals in the joint fluid, even with those, what I refer to as liquid TOFAS rather than solid tophis.

So it needs to be dense enough for the voxel to see the crystals. The voxel is just a cubic pixel. Trying not

There's use so much about gout that's so dramatic. I mean, that taste that comes out on the microscope, that makes for a great mural over the couch in your living room. They'll get me started. So anyway, we have more. Let's go to treatment.

What treatment should you the rheumatologist use to treat and resolve gouty tophi? This was a case I just saw, 50 year old guy who has had gout for, I don't know, ten, fifteen years, never treated. He came to me after he was hospitalized for bilateral septic knee arthritis. Yeah. With underlying tophaceous gout in many joints.

And it's a disaster. He's got tons of tophye. And right now, I won't give you my answer. But when I asked the rheumatologist, thirty percent will use higher doses of allopurinol, twenty five percent will use allopurinol, meaning that there's another subset who are willing to go higher. For buxastatin seventeen percent and a uricase agent, twenty eight percent of you are willing to use it to resolve multiple gouty tophi.

Do these answers, surprise you, Sarah?

They do. I think that the uricase percentage in particular, just thinking across there, there are about 40 rheumatologists in our practice. And I think thousands and thousands of patients and the number on pegilotta case is like probably five across all those doctors. And so I think that this is probably an overestimate of realistic use. I do think that there's a role for using uricase therapy.

And I'm actually curious about, you said your patient has never been treated, is that right? Never,

we just started febuxostat two months ago, and today we escalated the dose.

Okay. I think it's still gonna depend too on like how disfiguring are these Tofi, where are they? Are they on their fingertips and the person can't hold a pencil? They can't do their activities of daily living? Are they getting infected?

We have surgeons that we incorporate into some of our patients care, especially for those, a single toe where it's rupturing through or something. So that's not on the list here, but I think it's worth adding to the list is having your surgeon deal with maybe one of them. But I would start here with allopurinol and I would go up, unless they ended up that they're getting like rupturing through the fingers and affecting function right now.

John, what was your quote about your case therapies?

Your case therapies, I've called them over marketed and underutilized. Just when you look at national data, it's not used that much. And there's probably a lot of patients who could benefit from it. You know, I mean, I go very much with high dose allopurinol or a high dose combination therapy with xanthine oxidase inhibitor and a uricosuric to really try and push it down, push the urate level down. There was a very nice study by Doctor.

Perez Ruiz who looked at urate levels and the rapidity of Tofus resolution. And the lower the urate level, the faster the Tofi resolved. But that was measured in, you know, fractions of millimeters per month. So, the Tofi actually, I mean, they respond faster than the inflammatory disease because you'll see in trials that the TOFA gets better within the first year and the inflammatory disease might take a little longer to really settle down. So dose escalation works quite well.

Now I'll work with the patient to see how quickly they want it down. If there is an indication for debulking, for example, very painful tofus in plantar fascia where walking is limited. I would rather not do surgery because healing can often be difficult after a tofus resection. And so that's a good indication for your case agent.

The problem as I see it is one is you say the under utilization and a little bit of a hesitancy on using uricase therapies. But last week in our journal club on gout, we asked the audience about, will you escalate or what's the highest dose of allopurinol you use? It was like forty something percent of rheumatologists were afraid to escalate or weren't going to be escalating allopurinol in the face of renal insufficiency. And these are rheumatologists that are answering this question. So there's a lot of educational needs here that might be better.

We have one uricase drug on the market pegilodecase and we were about to have the nano encapsulated sirolimus pedrocase, but that's been put on hold pending a manufacturing issue that's being addressed with the FDA. But if we have another drug in the marketplace, hopefully there'll be more education and maybe there'll be more use. But, Nicola, how do we overcome this or are we just fine?

Well, I guess I'd just note and I know you have an international audience. You know, I work in a, I work outside The US. We have no access to peglodecase or uricase therapy at all. You are in a very lucky position compared to the rest of the world, in that respect. And so it's certainly in, you know, in countries where we don't have access to uricase, we get, I think, probably somewhat better at actually using oral therapies, particularly allopurinol and febuxostat.

And certainly in many Asian countries also, bensperomerone is very widely used as well. And that's a very effective urate lowering medication as well. I think I would just say is, is, you know, we have really good data, particularly from work done by Lisa Stamp that actually, you know, allopurinol often does need higher doses above three hundred milligrams daily to achieve even a serum rate target below six milligrams per deciliter. And we, you know, for someone who's got multiple TOFI, we need to be consistently getting that urate below five or zero point three zero millimoles per liter. So, you know, that does often require doses of allopurinol of five hundred, six hundred milligrams, and or addition of uricosuric therapies, and combination or combination of febuxostat with uricosuric, drugs.

So, you know, I think especially once you've got people who have extensive trophaceous disease, it often takes years with oral therapy, especially if you're not really getting that serum urate down. And TOFI are very disabling. They have a major impact on joint function. They're actually very distressing psychologically for patients as well because of the cosmetic issues, you know, when they're getting infected and know, a, we should be trying to avoid them with earlier urate lowering therapy. But once they're there, we do need to absolutely treat them intensively.

And we can get the serum urate down to target with oral therapy. We've shown that in our trials. But it does require, you know, some proactive dose escalation and not just sitting at allopurinol three hundred milligrams, one hundred milligrams.

Yeah, those studies that Nicola was referencing, it's body weight and pretreatment urate, which I consider a very cheap genetic test for urate transporters. And that's what drives the dose that's going to be needed. It's less renal function. Renal function is important because you don't want to start with a high dose, but the daily clearance, it is going be driven by other factors.

And I would also add in that, we don't have a nephrologist here, but I think that there is a subset of nephrologists that have a very big interest in gout and using synthetic oxidase inhibitors and feel very friendly towards these higher doses of allopurinol that we're talking about. So I think if there's a potential concern that the medication itself is going to harm the kidney, that is not the concern. And we're worried potentially in the beginning part about having allopurinol hypersensitivity syndrome, and therefore we're starting the initial allopurinol is a lower dose. But think I that again, nephrologists are recognizing more and more that we can escalate safely and is not going to cause renal damage. Anybody else to contribute to that?

I want to interject into the discussion here, something non script and that is the gigantic problem of education. Twelve point one million Americans have gout, but only one point three percent will be seen by rheumatologists. And that means gout is being managed by people who know less than rheumatologists where their average dose of allopurinol is three hundred milligrams. And what's the average dose of allopurinol by rheumatologists? Three hundred milligrams.

So I'm just gonna ask each of you, I'm giving you a magic educational wand. Where would you start? What's the one thing you would do to substantially change education on gout and its management? And we'll start with Nicholas, Sarah, and then John. Nicola, what would you do?

I'd train nurses to do it, because I think we have really good data that nurses, nurse led care is much better than probably anyone else's care. Rheumatologists, primary care physician, you know, if we actually have trained nurses delivering education, we've seen that in clinical trials that leads to incredibly impressive outcomes. So that would be my intervention.

Excellent, Sarah.

Mine is a bit of a different flavor of the same, which is with pharmacists. And I think from a systems level, if you can get the pharmacist to print onto the label, after one month, call your rheumatologist, ask them for either a blood test or a higher dose or something, then you've got the pharmacist just pushing it to the patient. Oh, I'm getting the refill. I've got to call my doctor and ask them maybe they need to call their nurse instead, but put it on the label.

John, what would you do if you're gonna change gout within the VA system?

So the VA has a database that's been set up by the San Francisco group where we can look at who's on who's on urate lowering and what their uric acid levels are. And we can do QI programs on that. We've had we've had nurses work on that. There's a clinical trial that's using pharmacists in the VA to do this. And I expect that that's gonna be very good.

Adherence is a really important issue. And I think the goal and the key to adherence is patient education and understanding. And that's both a lot of nurse visits in The UK study, educated patients, pharmacists being involved to educate patients. Patients will frequently say, I wish I started my treatments earlier. That's when they've, you know, years later have been educated.

So, I think patient education is the key and anything that improves patient education is going to be helpful.

Okay, let's go on with our next questions. These have to do with what specific and what sensitive in imaging. So in established gout, which imaging is most specific? Best answer was thirty eight percent said DECT, thirty seven percent said I don't need imaging in established gout. And then sixteen percent thought ultrasound was most specific and then eight percent said x-ray is specific enough.

Sarah, what do you think is most specific in established gout? Assuming that you're going to do it or have to do it, whatever, what is most specific as far as established gout?

I mean, I think this is asking about if you have a joint from which you've taken synovial fluid and you know that the fluid had crystals. I mean, I think that that's how a lot of the studies report these So we're not using the physician diagnosis as the standard we're using like synovial fluid as the reference test and DECT is very highly specific. Ultrasound is also very specific. I don't know if I actually don't know off the top of my head head to head which one, they're both in the high 90s. DECT is in the, I think the very high 90s.

No one knows better, but I think that the you know, decked has its there's a potential for, you can have a false negative, but it's, for somebody who has established, you know, long standing gout, it's this is not about sensitivity. This is like you see something there, and it's a green color coded on your software versus it's absent, I think I think decked.

John, you noticed that she's picking a fight with you. Right?

No. DECT is more specific. You can be confused aggregates. You can't tell if there's CPPD or MSU aggregates. The double contour is more specific, but of course there's something called the pseudo double contour.

The CPB crystals form in the cartilage or the fibrocartilage, the MSU crystals are more likely on top of the cartilage. Within cartilage, it gets very hard to decide in or on top of. So yeah, the ultrasound is less specific.

Excellent. Nicole, what do you think is about this other question about what's most sensitive? And this is an early disease.

Yeah, And John I alluded to

the fact that DECT is not so good in early disease. And they said it's the double contour sign is probably the

most Yeah, think that's fair. I think certainly there are, I think we do certainly see in people with very early presentations, which is really where you're probably using imaging for diagnostic purposes, is, it's not that unusual to have a totally normal dual energy. And again, that's for the reasons that John was talking about that you really need a large enough volume of crystals clumped together to actually see a deposit, with dual energy. So I think ultrasound does have higher, sensitivity. And I think the double contour is certainly something that does is present very early, early on.

So that is, I think that would be I think the majority rule is, correct. And I think the other thing just really to say here is, I think the audience here is very aware that the imaging features of joint damage, so arose of disease, really occur so late in disease presentation, most of the time that that's really not useful diagnostically, unless you're trying to exclude some other condition, maybe psoriatic arthritis where you may see some very early erosive disease, but ultimately that's the most of the conditions we treat. Know, plain radiography is not going to be that useful diagnostically.

I like that the audience said that in early disease, imaging is not required. That was a selection by ten, nine percent of people. I think that that's true. But should imaging be required in people who have a diagnosis of gout for whether it be x-ray or ultrasound or even that? Doctor.

So I might just come back to my, my initial comment about we are physicians and we incorporate when we're making diagnoses, we incorporate all relevant information, and integrate and synthesize that into a diagnosis. I think there are certainly many situations where actually, you know, it's looks like classic gout, you know, a person who's presenting with recurrent episodes of podagra, who, has hyperuricemia, where there's that typical time period of, you know, painless and critical periods, you know, I think in that situation, I would be quite comfortable to make a diagnosis of gout without imaging. If a patient presents with classic tophaceous disease, actually, I think that's so clinically typical that you don't need imaging. So I think, I think there are many situations where actually we need neither arthrocentesis or imaging personally.

And I think sometimes where we've talked about this already, but just to go back to the sort of the bedside ultrasound or just really having imaging as a teaching tool for a patient, I agree with Nickel very much that there's clinical scenarios that are so common that we don't need imaging, but then there are also patients who say, well, I don't wanna take medication. And if you can show them, look, you already have damage in your bone, you already have this, look at this snowstorm looking aggregate on your toe, this is a problem, this is underneath your skin. That can be convincing in terms of starting treatment.

You really should have, every rheumatologist should have one of those Christmas snow globes in the exam room.

That's probably a shape like a toe.

We'll start marketing that. But your answer answered this question from one of our attendees who said, patients wanna know, can they stop their allopurinol? But I think that when you have that imaging says, do you really wanna stop the allopurinol with what I'm showing you here? Do you think that? Because obviously my patients don't wanna know, they just go ahead and do it, right?

That's our biggest problem. And that goes to John's quest for patient education, which is I think the holy grail in gout management.

All right. Yeah, have been studies, it was called the dirty dish hypothesis. If you clean the joint well enough, what happens when you come off your urate lowering medicine? And it all depends on what your uric acid is when you come off. And so if you've made other changes, med changes, you know, you're off your thiazide, now you're on an SGL two eye, you know, and you know, if you've you've lost weight, you know, if you've done things that can change, you know, you can't change, I tell patients, you can't change your parents.

So, genetics can't get changed. The transporters don't change but if there are other things you've done so that now, your urate could be below six, you're very unlikely to have a flare again if you can keep if the uric acid is low after whatever's whatever changes have been made.

But I'd also say that the majority of the time when people stop their ULT, it's time you're at most immediate one of

the week. Streaming back.

High level, and then they're at risk of forming crystals again. Yeah. So, yeah.

But there is hope and I love it when you can give patients hope goals and roles, especially when managing gout. But they obviously need to rely on you for their next move. We alluded to this earlier, John, you want to explain this why calcium pyrophosphate disease may get confused with gout on ultrasound?

Yes, so calcium pyrophosphate has hyperechoic aggregates as well. They also have suspended aggregates in synovium, which is the snowstorm description. And then, as I mentioned, the double contours, you know, there's a pseudo double contour. So, that can be difficult. I actually don't know the perineural hypervascularity.

I think I made that one up. Okay.

I'm glad I didn't make up an answer on that then.

Well, but how do you distinguish pseudo from real double contour signs? Is it experience?

So some of it is location. So if it's in the knee and you have thick enough cartilage, you can see if it's in the cartilage versus on the cartilage. That's kind of a Sesame Street thing that we're trying to figure out there. The other is the capsule will have CPP deposition, and the capsule sitting on the cartilage can look like an MSU double contour sign that's on top of the cartilage. And if you move the joint there's a nice video with this one example showing that the cartilage MSU crystals move with the cartilage because they're attached to the cartilage, and the CPB crystals stay where the joint capsule is.

So those don't move. So there's little tricks, but it's, I mean, caution. And know, after you've made a number of mistakes, you start becoming more humble about how certain you are. So, yeah, caution and experience, I think, help.

Excellent. Can I maybe just ask John and Sarah, who are the sort of do a lot more of a lot more ultrasound expert than me? So how often would it be that you would see in a person with, you know, where you're uncertain whether they've got gout or CPPD? Presumably most of the time with CPPD, you're going to see typical deposits within the femoral articular cartilage, you know, that and other features of CPPD, not just a sort of single double contour. Yeah,

I was just thinking as John was speaking, the joint really matters. So if it's person has the first MTP affected, just clinically, it's very unlikely to be CPBD in that joint. I think the knee is a very canonical joint for the ultrasound. And in addition to the location of the crystals being different in gout and CPBD, the appearance of the deposits is also somewhat different. With gout, the layering of the monosodium array is a little bit smoother on top of the cartilage, whereas the CPP deposits are more like chunky or stippled within the cartilage.

So that's a nice bedside test that just as you said that in your clinic for anybody with gout, you'll look at the first MTP, which I think is very, you know, very nice to do. If you're looking at the knee, if you're looking at somebody with an undifferentiated potentially crystalline arthritis, looking at both knees is an excellent test. And then also the wrist for CPP crystals. If you'd be looking at the triangular fibrocartilage complex in the wrist and you see something that's hyperechoic, that would be unlikely by the location to be monosodium urate.

And it's not uncommon to have both. Would just point that out as one doesn't rule out the other.

So we have but a few more questions. If the audience has any final questions for our panel, please get them into the Q and A box. But we're gonna end with two survey questions on gout. How often are people using? And I agree with what's been said here that seems like very few of us are using it and 51% said they don't use deck scanning, 28% they sometimes use deck scanning almost as if to say, know I should answer yes here, but I'm not sure what I should say.

18% of you said rarely, and there's this number here, which is probably around four percent say that they're doing it often. We also ask what are the limitations and we've talked about that before. The audience correctly said it's cost, it's insensitivity and early disease. These are the two big factors, availability or payment and then insensitivity at the right time, radiation exposure, and six percent thought artifacts and false positives were a big issue. Why don't each of you take a stab at some of the claims that are made on this slide as we wrap this up?

John, why don't you begin?

So I think I was, sorry, I was trying to also read some of the questions in the Q and A. So the limitations of DECT is I think the early sensitivity, it's the access to the machine. You can usually get I usually am able to get the insurers to pay for a single extremity deck. The radiologist always want me to order bilateral because they're going to do it anyway. And that never gets approved.

Were there other, what was the other question

you had? No, that's good. I want you to just pick out one important point. I think that's a very important one. Sarah, what stands out for you?

I think the use of DECT, we've already heard from the audience about limitations of availability, but I think to the points that we've been discussing today that we can use ultrasound as a first line modality. And even if you yourself are not performing it, hopefully people have access to musculoskeletal radiologists or general radiology group that's able to do an ultrasound as of first line test.

Okay, and Nicole?

Yeah, I just talked, I'd like to talk a little bit more about the artifacts because I think that's a real issue with dual energy. And I think you really want to be looking at these images yourself. It's very common to see green signal, particularly around nails, around thickened skin. Often there's quite a lot of other sort of beam hardening and other movement artifacts. So I think if you're getting a signal, you want to be really sure that it's actually a typical signal that is consistent with dual energy.

So you want with MSU, I should say. So you really want a radiologist who's used to looking at these, and you want to be looking at the images yourself and actually thinking, is this deposit actually within a nail bed or is this a deposit within the first MTP joint at a site where I know that this person's actually had symptoms? So I think again, you know, as with all imaging, it's that, you know, correlation and aligning with your clinical assessment as well, which is really important, particularly when it comes to dual energy CT.

And I think that's important. There's some innovative thoughts on imaging spine and discs and costo cartilage and heart and those all get much more challenging and figuring out fact from fiction. Yeah. Gets it gets very difficult because yeah. Yeah.

And that's where you ideally want some crystal confirmation when you're thinking along those lines.

I put a little factoid up this month on the website about axial gout and that depending on how you do it, it can be seen like ten to twenty percent of the time and whatnot. Is this a realistic issue that you mavens deal with? And how do you prove the point?

So I think there

is definitely diagnosis of this guidance.

Definitely gout can present in the spine or in the SI joints. That's typically in people with really severe tophaceous gout, where the diagnosis of gout is, you know, in question. And then the question really is, is this acute presentation of back pain, due to gout or something else? And I think in that situation, just conventional CT or dual energy CT can be really helpful. I think there are a lot of studies of dual energy CTs, in people with gout without gout, where as John has indicated, you see a whole lot of green signal in the costal cartilage intervertebral disc, in the SI joints.

I think probably most of that is artifact rather than true MSU crystal deposition based on the on our studies and my reading of the studies. But I think there's a bit of there's a bit of sort of variable views on that. But I think you again, you really need to be thinking about it in the clinical context.

So Doctor. Fung throws back onto us our title, What lies beneath? What do you do when someone has asymptomatic hyperuricemia? Will all this imaging change your mind? No attacks, uric acid of nine, should you be doing ultrasound to look for double contours, or deck scanning?

If it was positive, are you going to treat or is this a tree falling in the woods and no one caring?

So there's a couple, I think interesting paths there. I think I'm remembering the data correctly here. Thirty percent of patients with asymptomatic hyperuricemia never go on to develop gout. And that's from population studies. Japanese guidelines, however, say if your urates greater than nine, you ought to start therapy.

There have been a lot of randomized controlled trials trying to find benefits of allopurinol for other indications. You know, renal effects, cardiovascular effects, and those those have been disappointing over the years. You know, I I don't think we've given up on that. You know, the I I'm a fan of of of having patients weigh in on how much they want to avoid a medicine versus avoid an attack and then, Doctor Dolbeth is hopefully going to have evidence based answers on this shortly.

Yeah. So we've done a couple of we've of run a couple of studies on this. We did a dual energy CT study, and we've also got the longitudinal tiger study. And what we know is that sort of twenty to thirty percent of people with asymptomatic hyperuricemia with a serum rate sort of above eight will have MSU crystal deposition on, on ultrasound or dual energy. And the question, the big question, which I think your, panellists or your, Doctor.

Fong is really trying to address is, you know, should the do those people actually have gout and should they be treated with urate lowering therapy? And, and I think we don't really have any good evidence of benefit. Urate lowering therapy is associated with some risks, you know, including allopurinol hypersensitivity. So we need to be really sure that there's a good evidence base for people to be prescribed these therapies. And I think to date, the data really don't support treating in that very early stage.

As part of our tiger study, we've also asked patients about their views about whether they'd be willing to take a urate lowering medicine, if they have asymptomatic hyperuricemia, and most don't think it's necessary. And, and so I think given what we know already about adherence with urate lowering therapy, even in people with established gout, I think the uptake would probably be very low. And I think we really want would want to have much more compelling data to support that before we actually recommended that. So at the moment, it's not recommended.

Okay. All right. I want to, thank our audience for, spending their Tuesday night with the titans of gout. Our panel has been fabulous tonight. Thank you so much for your contributions.

I wanna remind the audience next Tuesday night, we have another panel, Ted Mickels, Mike Pillinger and Lisa Stamp who was referenced here quite a bit tonight. We're gonna talk about upgrading and maximizing your use of classic therapies in gout. That's next Tuesday night. We'll see you then. Thanks so much.

Bye bye.

Bye bye.

Bye.