Noting that gout is common yet under-recognized and undertreated, rheumatologist Kerstin Morehead, MD, presents a valuable update on risk factors, associated conditions, and treatments for both acute flares and chronic disease. She explains how to distinguish gout from rheumatoid arthritis; describes the potential consequences – such as severe joint damage – from lack of appropriate treatment; and provides essential info on medication safety and dosing protocols. Also: Learn gender-specific dietary modifications to offer patients.
thank you for having me here. I'm very excited to be talking about gout. Um I primarily work in clinical work at Parnassus um U. C. S. F. And I'm in charge of also resident education at Parnassus as well. So I see a lot of gout. I'm going to turn off my camera cause it's a little bit distracting and then we'll get underway. Alright I like talking about doubt not just because it's pretty under the microscope but also because it's a severely under recognized and undertreated disease. In fact with modern rheumatoid arthritis treatments I would say the patients that I see who have disabling joint damage or 24 more likely to be gout patients than R. A. Patients. And unfortunately there was a M. A. Guidelines that were published a couple of years ago that severely restricted treatment. So I'd like to sort of try to undo that. So the goals for this truck primarily since you all are on the front lines is to sort of put out on your radar especially gout that's turning into a chronic problem. So we'll talk a little bit about the differences between an acute attack and grow chronic out. Um Mostly because there are different treatment approaches for both. And I'll give you a few updates and path of physiology, diagnosis and treatment. Um But I'll keep the science at the minimum and I'll always show you sexy science. I really want this talk to be more of a practical for you guys. So I'll start out with a little bit of the path of physiology. Then we'll talk about risk factors and associated conditions because those play an important part not only in the genesis of gout but also on your considerations for treatment. Then we'll talk briefly about clinical presentations and some of the newer tools for diagnosis and finally we'll spend a good deal of time talking about approaches to treatment. Treatment is a little bit problematic when people have comorbidities and unfortunately most people with gout have comorbidities. So just sort of a snapshot of gout. It's very common and treatable inflammatory arthritis. It affects about 4% of people in the us. What happens is is that you get deposition of monosodium yuri crystals in and around tissues and joints and the way you get those crystals is that you have increased your aid concentration. Uric acid comes from de novo synthesis in the body also can be ingested and when cells turn over they release their D. N. A. Into the bloodstream and that's a major source of uric acid. What happens then is when the uric acid crystals deposit themselves that induces a really severe inflammatory response. In fact um they were just talking about a gout flare and the classic description is that it's so painful. You can't even have a sheet on the effective joint treatment of acute gout flares tends to be geared towards reducing the inflammatory response but to really treat chronic out to prevent destruction of joints and other comorbidities. You really want to reduce the uric acid burden and dissolve the crystals. So hyper your see me a sort of comes in a progression of um instances. The first one is people who have hyper see mia without crystal deposition. Then you can get crystal deposition but no symptoms. And then you get periodic acute intermittent arthritis of what we think of as a classic gout flare after time. This can become a chronic arthritis with deposition of crystals called trophy that are destructive to the joints and other tissues. And these also produce the radiographic changes that are classic of doubt. This is not a done deal. It's not necessarily a rule that things are going to progress this way. So hyperglycemia can be a little bit confusing to think about because it has sort of different clinical and physiologic implications. You really often need a serum uric acid level above eight mg per deciliter to have a gout flare. That's typically when they start to happen physiologically though, things start getting going when you have your gas at level of six or more milligrams per deciliter. And that's why that ends up being one of our treatment goals uric acid is typically excreted through the kidneys and the G. I. Track and the way that it builds up is typically because there's a fault in this expression. So these are under X creatures as we call them. And you can see this in renal disease and G. I. Disease. And as you know, the G. I can cause imbalances in the acid base metabolism which can then affect the kidneys. So it can be both that are effective in terms of the under excretion. I think I skipped this side. So the where and why and how and when crystals are formed has a lot to depend on the temperature. Um And the ph around that area and the salt concentration around that area, that's why paid agra. The large toe involvement is sort of the classic presentation and that's because that's a very cold joint, that's a small joint. And so the ph and salt concentration really predisposed towards being sort of the first place you and you end up getting a flare. Mhm. So this is a little bit of the path of physiology as we understand it now. It starts with the innate immune system. When monos sites ingest crystals, they then activate what's called an inflammatory zone. And basically what an inflammatory is is just an aggregate of polymers that induce the immune response. In this case the immune response is interleukin beta and also something called nets that we'll talk about in just a minute in order to produce the interleukin beta. However there has to be a second signal on the toll receptor. And let me see if I get my pointer here and I'll show you so you get the hyper your ischemia, you get the deposition of crystals. These are the crystals ingested by the macro on a site. this is the inflammatory zone. And here's a toll like receptor that then induces the inflammatory zone to make interleukin one beta. The second signal is very interesting. Um We think that it's probably fatty assets and oxidized LDL so that obviously has implications on what we think of the typical dietary. No nos for gout. So high fat foods, high cholesterol foods. Also another interesting thing is toll like receptors are very instrumental in the body's surveillance for cancer cells and also keeping those cancer cells in check. So there's a hypothesis that gout is actually a beneficial adaptation that really sends an alarm signal that there's something amiss in terms of cells that have uncontrolled growth. So these are nets and you see these lacy things here these are net stands for neutrophils extra cellular trap. And what happens is is that the neutrophils spew out this lacy material that entrap things. And here you can see they're entrapping bacteria when these nets are activated by the inflammatory zone they bind the uric crystals and you get resolution of their building up however they can also be activated without the inflammatory zone. And it's thought that these nets actually end up being the scaffolding for toll fraud. Yeah. So looking again at this slide you can see the uric acid is ingested, it activates the inflammatory zone you have a second receptor here you get interleukin beta Annette can come out and if it's with pro inflammatory molecules you get degradation of the uric acid crystals. But if you don't you just get uric acid crystals and a net you can get to five formation. There is also adaptive immunity involved in the gout response. Um T helper cells are activated and they produce aisle 22 and I'll 17 over expression. Um As you may or may not know these, I'll. Inner Lukens are very instrumental in psoriatic arthritis. So for psoriatic arthritis, patients have a double hit in terms of being at risk for gout, not only with this over expression, but also because high cell turnover is a large source of curing which then turns into uric acid. As the uric acid crystals build up, they become trophy, which also become erode sieve in bones. The flares tend to worsen and to last longer. And finally it's essentially one big flare. You get pain during intercourse. Ical periods. This takes about 10 years after the advance of an acute attack and typically the serum uric acid tends to be fairly high like above 10. You get to sit about 3-6% of men and 1-2% of women. And that's because estrogen is instrumental in helping clear your gas it through the kidneys. This prevalence will increase with age until people get about 70 and then it tends to level off. There are very strong associations with other disorders. Um the main one being hypertension and this is mostly because of oxidative stress, chronic kidney disease can also have an effect. And as you can imagine that it affects the way that your gas it is cleared. Obesity is also an interesting risk factor. It also was thought to be due to activate its stress and then there was that second toll like receptor hit that we saw with the fatty acids and diabetes as well for a variety of recent oxidative stress effect on kidneys and things like that. Um It is a risk factor for cardiovascular events. Ingestions are also independent of weight can precipitate effects fairly easy. Alcohol is a big one. Red meat is another one and sugary drinks again independent of weight can precipitate effects. Lead is also um sort of an ingestion. We it's called Saturn. I got we got this from the romans who used to line their wine vessels with lead and during saturnalia which was one of their big festivals there was a huge increase in gout. Um you can also see a lot of this with people immigrating from china drugs are a big risk factor for precipitating out effects diuretics for obvious reasons cyclists for in paris and um I'd ace inhibitors and a R. P. S. Are a little bit murky as they often are when the renal function is affected there very good at reducing hypertension so that helps gout but it's also they can affect. The kidneys which can hurt gout. Rihanna beer beta blockers and low dose aspirin which um affects the way the kidney clears uric acid. Other risk factors include age for a variety of reasons menopause again, because estrogen helps the kidneys clear uric acid psoriasis for a couple of reasons that we talked about him a geologic malignancies. Again, increased cell turnover, which leads to increased curing load anemia, which is usually involved with oxidative stress as is trauma. So one classic history that you can often get if someone has a repetitive injury that can precipitate a gout flare. So people going on hikes, people operating jackhammers, that sort of thing. Genetic risk factors are pretty obvious from the genome wide associations. It basically has to do with your metabolism. So you're a transporters metabolic pathways and that's why at this point serum uric acid control remains our key for preventing and treating chronic out. There are gene environment interactions that are not well understood just as their gene gender interactions as well and epi genetics. This work is just starting to get under way as an area of interest. So I think we're all familiar with the typical presentation of gout. Um paid agora, the great toe being the classic example. Gout can affect any joint in the body however. And here you see a large Tofas in the T spine. You can also get different atypical presentations of God. Um systemic symptoms are very common fever. Toaff. I can present before people have an actual flare that they recognize. Again, we think of it as affecting the peripheral small joints but it can also affect ask seal joints. You can get extra articular manifestations, particularly cardiovascular disease, kidney disease stroke and renal failure. Mhm. The gold standard for diagnostic evaluation remains being able to see crystals under the microscope. However, in reality this happens fairly infrequently. The serum uric acid level can be problematic during an acute attack because it is often seriously low. Nonetheless, we usually send it just to get another data point. You can sometimes see a model glucose psychosis and typically you do see elevations in the inflammatory parameters. The earth aside sedimentation rate and the c reactive protein. Tofu can show up on the soft tissues. Um So places like the ears are pretty classic. And here you see some examples of that tendons. So elbows and achilles are places where uric acid crystals often build up and cause problems and then when Tofik build up in the joint. That is what we think of as a gaudy erosion. That's actually a Tofas. Oops, sorry X rays are also helpful in evaluating it. You can see soft tissue swelling. You can see cystic changes in the bones which are sort of non specific but can be indicative of early erosive changes. There is the classic rat bite erosion that is a coordinated erosion that is away from the joint and that's to distinguish it from, say rheumatoid erosions where you they're not core dedicated and they're close to the joint line. However these changes can also look a lot like inflammatory osteoarthritis which is to say osteo fight formation with joint space narrowing and psoriatic arthritis where you get this kind of resort option of bone and erratic osteo fight growth here is um a classic a set of erosions. This is a slide from the A. C. R. But I actually have several of these in my collection here. You can see Kordic aged bone where you see it's wider than usual and it's got this classic kind of overhang like a rat bite. This is the joint line. This by the way is A. D. I. P. Um And here you can see another erosion Again the core dedication and the overhang shape of it. Here's another example where you see a really horrible Tofas here with soft tissue swelling and then in the metacarpal in mid foot you can see these cystic changes. Newer modalities include ultrasound where you see something called the double contour side which is a sort of a preto fi build up of uric acid along the joint line which is here. It's not Quite ready for prime time at this point it is very operated dependent and so it varies not only from institution to institution but also radiologists radiologists and it's not particularly sensitive. That's a wide base here but you know at best 80% probably more like 40-50% and it's also not entirely specific. Although it's a little bit has a little bit of specificity than than sensitivity. What's a little bit better is seeing both a Tofas and a double sign. So there's the Tofas there and that increases the sensitivity and specificity quite a bit. Again, not sure you're getting much more than a general radiographs about with this because once you see a tau phi that ship is sort of sailed and it's a little bit late for treat. I mean you definitely want to treat it but we do like to get people treated before they develop tau phi and erosions. One of the newer things is a dual energy ct which has a little bit more sensitivity and specificity than the ultrasound. And it can pick up Tau Phi. And people who are asymptomatic Lee, happy your ischemic. Um in fact on one study, 25% of a group I think of about 200 had had findings. So it's better for ultrasound than extra articular deposits. Um and that means deposits along the Tendon lines that you see. It does tend to underestimate the size of tofu and it doesn't detect inflammation. So it's a little bit difficult to know if that people have active disease, although an active gout attack is generally pretty obvious in early disease. Again, it's not quite as sensitive and so not quite as helpful in terms of really understanding if people have trophy or not. But it's pretty cool. This is what it looks like and you can see the trophy here and here and so we're getting these more and more and we're finding them fairly helpful one way in which they're very helpful and I've had a couple cases of this is that as you know, the differential diagnosis of a gout attack can be an infected joint, it can be pseudo gout, it can be rheumatoid arthritis, it can be psoriatic arthritis and all these things can coexist together. So I found it very helpful in people with psoriatic arthritis who also have gao determining what processes causing the destruction or both of them are causing the destruction. Because you won't see this light up and say just a regular erosion, calcium pyre phosphate disease. A little bit confusing. I can't quite get a straight answer from the radiologist about whether that shows up on gout or not. So I'm sorry, on the ct or not. So that I think is a work still in progress. But that would also be very helpful because calcium pyro phosphate deposition disease can really fake you out for things like rheumatoid arthritis and inflammatory osteoarthritis. So moving on to treatments and this will be the bulk of the talk because I think this is the most important part for us. Typically the teaching is you don't treat a symptomatic hyperglycemia, but we'll talk a little bit more about that because I do think there are instances when it should be addressed in acute attacks. Your ghoul is usually just to reduce the symptoms and make the patient more comfortable and the faster you can do that is usually the better for chronic treatment. What you're looking for is a long term reduction in the serum uric acid concentration. And when we define chronic that's defined as more than one flare per year or people who have tau phi either interoffice ius or cutaneous if they have greater than stage two kidney disease, it's often um thought that it's a good idea to go ahead and treat and if they have renal calculus i that are uric acid stones, obviously that's an indication as well. So asymptomatic hyper your see mia um the party line is that it's not recommended. However, if the uric acid is greater than 10, the thinking is you know, they don't have to find now they're definitely going to get trophy. And it's also if you can see if they have to fi even though they're asymptomatic then that's also an indication to treat and that's where the imaging becomes so important. So there's a lot of discussion about lifestyle modification and what to do about this goes in and out of fashion. Um over the years with different fads coming into play and that's because the data are very mixed and conflicting weight loss is always thought to be a good idea. But as a professor of mine used to say the body is not a chemistry set and especially the immune system. So you can often get paradoxical reactions in things that seem like a good idea. So weight loss actually leads to the um doesn't really affect the uric acid levels and you get the thinking behind it is that it leads to decrease denove appearance or in parenthesis. Excuse me. And also insulin can reduce renal pureeing excretion. That being said, there are some actually decent data on the dash or mediterranean diet. Um, it tends to be more effective in men than women and it tends to be more effective in people who have pretty high uric acid levels and it's also good for treating the associated diseases. So things like hypertension, diabetes, obesity, other lifestyle modification. We all hear that lagoons are precipitates of gout flares, but they're actually okay for everyone in moderation for women specifically, avoidance of red meat seems to have a positive effect on gout flares for men, vitamin C avoidance is seems to have a positive effect. And all people should avoid high dose high dose fructose. Other things that seem to have a trend towards being effective are low fat dairy. Um a low protein, low pureeing diet, increased intake of short chain fatty acids and that's probably because of the fiber in most of the carbs that are recommended with those and then polyphenols, which are things like barry and grains and that's probably where the whole cherry juice mythology comes from alcohol is a definite no, no, because it's a triple threat. It not only increases oxidative stress by converting A. T. P. Two and P. It's very dehydrating and it can cause a metabolic acidosis that affects the renal clearance of your eight beer ends up being a quadruple threat because it also delivers a huge pureeing load. So treatment for acute flares are pretty familiar probably to everyone except for the last one, the ill one inhibitors. Um Typically you start with Culture Scene or Nsaids and steroids tend to be reserved for people with comorbidities. Culture scene is a very interesting drug in terms of its history. It's been around for a very long time. There is evidence that the cro magnons people used it for probably gout flares. It comes from the statement of the crocus similar to saffron and it has um unfortunately even though it has an interesting history, it's not a particularly good drug and it has a lot of potential for toxicity. In fact every year in the hospital will have an Eminem about culture scene overdose it can cause renal failure, it can cause a paddock failure, it can cause a bland myopathy. Um it can cause neuropathy and with chronic use it can cause bone marrow suppression. It's also not a very effective drug you really need to start it, They say within 12 hours of onset, but probably the first tickle of a gout flare and most important, it doesn't alter the progression of disease. And so it only treats in the short term. And so it doesn't prevent things like toe five formation or monosodium your crystal formation. We used to say take it until you get diarrhea. Um So you can imagine that was pretty unpleasant, especially if you were taking enough to induce something like a myopathy. But a recent new protocol has been recommended and that's where you take two pills followed by one pill in an hour or so and then once a day until the flares of sides. This tends to have a lot fewer gi side effects. You do want to reduce the dose in kidney disease. Um And if people are using the cytochrome P. 4 50 inhibitors like macro lives antifungal zor HIV meds and you want to be very careful in people who have liver disease as well or who are using statins at the same time. N sets or another. Mainstay of treatment. The teaching is in the medicine is the go to drug but there's really no data for that. So it doesn't look like one class is better than another and I'm sure you all are aware of the potential side effects. So you can get gi irritation and bleeding P. P. I. S. Can help mitigate this but only in the upper G. I tract. You can get renal toxicity which becomes an issue for a lot of these patients. It can magnify or even induced hypertension. It's not good for congestive heart failure patients. It has anti platelet effects which make it an issue when people who are on prophylactic aspirin or warfarin. If you have a patient who was taking aspirin or in um what you want to do is make sure that they pace out the inset at least four hours before or after They take their aspirin because the inside will temporarily block that site where the aspirin binds on the play lives. There is one exception to using Nsaids with Warfarin and that celecoxib it doesn't it interacts so you have to keep an eye on the level but it doesn't block or or potentially eight its effect. And like all drugs that can also cause a rash in patients with kidney disease or hepatic disease, we often use steroids. Um injections are a nice way to get around any co morbidity obviously. But if there are multiple joints or if after a while a flare tends to become diffuse involving the soft tissues that ends up not being so effective. The standard oral dose for steroids is typically much higher and you have to use it for much longer than you would think. So we start out with 30-60 mg and do it for with a slow taper for two weeks or even 21-30 days. One trick is you can board an attack if you give someone 20 mg for three days. Again at the first hint of the attack, steroids again, have a very familiar and very disturbing list of side effects. They can potentially eight hypertension. They can induce chf obviously they cause hyperglycemia. And with long term use there's osteoporosis and this happens and as little as five mg for more than two weeks in most people. And it's very clear that osteoporosis happens early in the steroid treatment. And so there will be new guidelines coming out and when to institute prophylaxis like bisphosphonates when you give people steroids, it can cause skin changes, which can be very problematic and older people because it's an immunosuppressive if you get a skin infection that will take much longer to heal and a lot of people are very sensitive to the cns and facts and so you get sleep disturbance, you can get me uh you can get anxiety And immune suppression can happen and doses as little as 2-5 mg, especially in older folks. So that's something to be aware of it. Also, again, at those very low doses looks like it reduces the efficacy of immunizations. So the response to the immunization is greatly diminished. I have one inhibitors um have come on the scene in the last five years or so and we typically use these in the hospital because they're so expensive. But anna Kendra is very ineffective in controlling a flare. It's given as an injectable and you do that once a day for three days. And that typically knocks, knocks it out quite well. And this has been very handy. And you know, the diabetic patient with congestive heart failure and chronic kidney disease can accumulate app theoretically should do the same thing, but it hasn't been tested enough or approved for this. Anakin ra is mildly immunosuppressive. So pharmacists are very adamant about TB screening beforehand and aggressive immunization as well. And as I mentioned, it's very expensive, which makes it pretty much an inpatient drug because the cost is so prohibitive. So moving on to chronic therapy. So the indications for uric acid lowering therapy include, as I said, more than one flare a year. Uh Sophie and renal called july. So the serum uric acid gold depends on the severity of the disease. If they just have a few gout attacks and no evidence of tau phi the goal is serum uric acid, six mg per deciliter. However, if they have Tofas and of any size and or severe gout or frequent attacks, then the goal is closer to five mg per deciliter. And frankly I tend to try to shoot for four milligrams per deciliter. So the again, the party line is that you begin uric acid lowering therapy two weeks after an acute flare. And the thinking behind this is that most of these medicines can actually precipitate a flare because they're mobilizing uric acid and making it more available to the immune system. However, usually when you're starting uric acid lowering therapy, people are in either prolonged flares or constant flares and it can be hard to get in there to start it. So it's generally okay to start it as long as that flare is pretty much controlled because you're gonna need to use prophylaxis anyway, you do want to monitor this year America as it frequently. That's every month for the first couple of months until you get to the goal unfortunately, um there's a problem with adherence for most of these medications. One of the reasons is is that there's a misunderstanding that they're going to help an acute flare. And so patients often feel that the medicine isn't doing much for them. As I mentioned before, The flare can actually be precipitated by the uric acid lowering therapy. And um even if you're at goal usually six months or even up to a year, you're still going to have breakthrough flares, but the importance of it is that it not only prevents acute attacks, it also prevents damage and disability down the line. So there are sort of three flavors with this. There are the Xanthan oxidase inhibitors that cell appear in all and ferocious stat there. The Uruk Oc, your ex um and that's pretty much prevented sit here in this country and then there's peg elated your case, which is again, probably more of a hospital thing remains first line for uric acid lowering therapy, you started at dosages of 50 to 100 mg a day. You want to keep a close eye on people's renal clearance. Remember that? It's also had a toxic remember that it's gonna need prophylaxis at least for a couple of weeks or until you get to goal. And remember that there is a severe hypersensitive reaction that can happen where people can get a desk a mating rash and even die of that. And people who are more prone to that tend to have an H. L. A. B. 58 01. And we thought that that was mostly people from asia. But it's turned out that it's much more widespread in this country. Especially mostly because there's less mon informa tion the population, it's generally very safe and very well tolerated. But you do want to be cautious and aware that at higher dosages uh people obviously with renal disease especially fluctuating renal disease in people with hepatic disease in people who also use diuretics because that can potentially ate it. And in people who use statins again because of the potentially ation. So before you start out of paranoia you want to check a complete metabolic panel to look for renal and kidney dysfunction and I am more and more checking the H. L. A. B. 58 almost everybody just because you'd hate to miss it. Typically assuming everything is is okay. You begin 100 mg per day and check a level after a month both of the serum uric acid and the cmp typical dose is 300 mg per day. But as I mentioned in my last slide, you can actually go up to 800 mg with proper monitoring if a T. F. R. Is less than 30 you do want to start at 50 mg per day if it's less than that, you even want to go lower and slower to drug interactions that are very important to think about is a South I. Prin and warfarin heparin is an anti metabolite chemotherapy but it's also used in autoimmune diseases. It can permanently suppress the bone marrow if it's a too high dosages. And so Allah parallels interaction with it can be very dangerous or four in the same thing as potentially aided by al appear in all and it's not cleared as much and so you can really increase people's risk of bleeding. The second xanthan oxidation huber is called the bushes stat or york. Um It starts at 40 mg per day and can go up to 80. It's cleared hypothetically. Um And there's limited data on dozing for people with pretty severe chronic kidney disease. It's thought that it's probably okay. It also needs prophylaxis like al appear in all. There may be some cross reactivity with haloperidol hypersensitivity. Um So be aware that you can still get a rash with it. The H. L. A. B. 20 sorry B. 58 is not a risk factor for that. There was some data that there was an increased cardiovascular deaths with it. Um But that has now been muddied a little bit by recent studies. The main study that was done was published in the U. N. Indian Journal quite a while ago. It was a multi center randomized control style trial that was looking at cardiac deaths in patients who took haloperidol versus those who took a fictitious stat after 32 months. The rate was pretty much equivalent a little bit higher in the food bushes stat group. However, the hazard ratio for all cause of death was higher in fictitious stat and cardiovascular mortality was also higher as well and that's why it has a black box warning. As I said, there were two studies published last year suggesting that this isn't the case. Um They're not quite as robust as this study but they're also, the data is less confusing with them but this is that um there was, and this was probably by the manufacturer. There was some more that it was more effective than 300 mg of haloperidol that doesn't look like it's the case. There again, a couple of studies last year that suggested that it's not there is less concern about chronic kidney disease with it. However, it is much more expensive and we really don't have the data if it actually prevents erosions. We're assuming that it does to monitor it. Again, you want to check a complete metabolic panel. You begin at 40 mg per month and again monitor monthly until you get to goal. I also think shared decision making is a good idea. And so there should be a frank discussion about the risk versus the benefit probenecid is your sister york lowering agent. And you start out at 500 I'm sorry 105 100 mg twice a day. It is really excreted almost exclusively. So it's contraindicated with people with reduced granting clearances. It can also precipitate flares although we don't think about it as doing that that much. And it can precipitate your assets stones especially in people with toe fine. Um So it's typically avoided in people with sufficient scout. It can be used as monotherapy but it also is often combined with the santa knock season. So if you've maxed somebody out you could sometimes that prevents it. Sorry. Before starting. You do want to do a basic metabolic panel. I didn't start at the very lowest dose of 250 B. I. D. I. Monitor monthly and I counsel patients to increase their fluid intake. It can interact with aspirin and also with methotrexate. And so that becomes a concern in people who have psoriatic psoriasis and gout. Um And as we mentioned psoriasis is a risk factor for gout. We don't use methotrexate that much in treatment of psoriasis simply because there are better agents that are less toxic. But in some of the older folks who will see this, there was a medicine that was approved a while ago called Listerine Ad um and it was used usually as a combination pill with the sand stain oxidase inhibitors. Um It worked really well, but you needed to use it at pretty high dosage of 400 mg. However, it's been taken off the market because it's very toxic. Um So it's not available anymore in this country. You will however, see patients coming in from foreign countries who are bringing their medicines with them and they will be on it. So you do need to monitor their renal function quite close slowly to other agents that were never available in this country. But again, you will see people coming in from other countries, especially china are then Ben's bro Marone and sulfur pure zone. Um These are all very about a toxic um but there it's cleared originally. So that's why you keep an eye on the real function. Pig elated Fury case. Um As I mentioned is probably more of a hospital thing it's given in human logic malignancies to prevent kidney problems. However, after the first infusion, almost half patients have infusion reactions. Therefore, if we have to use this therapy chronically we tend to start people on methotrexate for a month beforehand and that seems to lower the incidents of infusion reactions. This is probably outside the scope of primary care a bit, I wanted you guys to hear about it. So prophylaxis. So when you start these uric acid lowering medicines, as I mentioned, you can precipitate a flare. So there are many strategies for preventing that culture scene is a good one. And people without kidney aerobatic disease. Um and you can start 1-2 pills every day and sets are also used. Although I have to say of all the medicines here and he's making the most uncomfortable in terms of their side effect profile. I like five mg to 10 mg of steroids. That can be very effective too. If the patient doesn't have diabetes, if you need more, you want to be slow on the uptake duration of it. The teaching is is that we're supposed to use it 3-6 months after you reach goal. However, in practical use, I think you know, you want to cut back on farm policy pharmacy. Um you want to improve compliance in the patients. So I tend to just use it until we hit goal. And although there is a subset of patients who will need these medicines as well as their uric acid lowering medicine to control their flares. And that's the people you continue indefinitely on other drugs that can have a mild effect on lowering uric acid are lost. Art in which is why there was the asterix next to a R. B. In our previous slide and fennel vibrate and this probably has to do with the way the gut functions. Um We talked a little bit about the metabolic balance of proper gut function. There are some new data to that the microbiome may affect the way uric acid is processed and cleared. So moving forward um as I mentioned, we're just starting to really take a close look at gout both in terms of its pathogenesis and hopefully that will lead to novel treatments. And hopefully the new imaging modalities will become sophisticated enough that we'll be able to really improve prognosis by having a quick and early diagnosis. So in summary acute gout and chronic out are a little bit different, both in terms of their presentation and treatment options and treatment implications. Do think about treating chronic out early reducing uric acid remains the cornerstone of therapy. And to sort of contradict myself from what I said a little bit earlier, no one ever died of gout especially not acute gout. So remember that all medications have potentially serious side effects. There will be a subset of patients who the only safe treatment will be paying control when you do start a medicine, you want to monitor closely, definitely consider their common abilities. And don't forget drug interactions
