TNR Grand Rounds - Evaluation Of Febrile Rheumatic Patients Part 1 Save

Hello. It is the April 14, and this is Tuesday night rheumatology, the grand round series. I'm Jack Cush, wearing my mask. It doesn't really fit, but I'm wearing my mask for a purpose. Everybody should be wearing these.

I don't know what the deal is. I was out twice today. I saw at least a third of the people in, you know, big box stores and in a grocery store not wearing a mask. Everyone's supposed to be wearing a mask in public. That's a CDC directive.

Doesn't have to be a N95 mask, it can be any mask, it can be a hanky that's you know, with that upper bands and as many easy ways to make facial coverings that cover the mouth and nose. Folks, we got to lead. In this crisis, we need leaders and we need people who are going to be led. You are the experts. People are looking to you for the information.

Why do we need to force this upon people? Because the numbers are still shocking. They're shockingly bad. You know, wrote on the website on the April 5 that we had nine thousand deaths in The United States. Five days later on the April 10, it was now over eighteen thousand.

And here we are on the April 14, and today it's over twenty five thousand. This is bad news stuff. Obviously, everybody should know that. And why someone can go to the store and not wear a mask and not be reprimanded for it. You should have heard me talk to the manager.

It wasn't nice. I was all over them like white on rice. So again, lead, make sure people are doing what they need to do in addition to social distancing and hygienic practice, it's all very, very important. I wanna bring to your attention one other important item before we get on with today's lecture, our grand round series for Tuesday night rheumatology. And that is the ACR has come out with COVID clinical care guidelines for rheumatic disease patients.

This was published on the eleventh after the executive committee approved the document that was formulated by a North American task force. That task force included 11 rheumatologists and four infectious disease specialists, and addressed a number of key clinical questions. I don't know how they did it, but they really came up with a pretty smart guidance document answering a lot of the questions that all of you had, a lot of the questions that we did address or tried to address in our town hall meeting. And I think you need to look at that. It's on our website.

I posted the link to the ACR website in the paper, in the publication on RheumNow. I sort of did a redo. I reordered their guidelines in accordance with the strength of recommendations. You should know that this was an expert consensus guideline because there are no guidelines on stuff like this. This is a crisis, this is an urgent situation for which data is going to be really in short supply.

So we need the consensus of experts. The things are graded as being either high consensus, moderate consensus or low. There were no low. There were some high, there was a lot of moderate or moderate to high consensus items. In general, they do support what we said all along, do not stop DMARDs because you're concerned about the Corona crisis or the COVID that's out there.

Again, for your patients who are stable, you're taking care of, you're doing telemedicine on, do not advise them to stop their medicines or stop their steroids or lower their steroids, or everybody should start hydroxychloroquine. Again, there's no evidence for any of that. They divided their recommendations up for people who are stable and who are either established patients who need ongoing care or new patients who have active disease who need ongoing care. And the bottom line is you treat them as you would normally treat them. The standards of care do not change and your job is to treat arthritis and immune diseases.

They have another category of patients who are, possibly positive and those who are definitely are suspected positive of having the corona, infection. And I think that there are some, important guidelines that you should look at. I think, again, you should read those on our website, on the ACR website. You should also read the report that we had from NICE in The United Kingdom. NICE came up with guidelines a week or so before the ACR that say some of the same things, they say some things differently.

And I like the way the NICE guidelines end. They end with the fact that you, the leaders, need to encourage your people, your coworkers, your employees, you need to maintain morale. You need to be the voice of reason, positivity and certainty, because everyone else doesn't really have those traits but you, because you're informed. Again, it's really easy to be confused and negative if you're listening to all the news. It's not so easy to step up and be positive and certain about what you're saying.

That's why we're doing these conferences, even having ran rounds. So today we're gonna talk about my favorite topic, febrile disorders in Still's disease, and how to evaluate febrile disorders in patients with rheumatic disease. So I'll start my talk by, sharing the screen and hopefully you'll see what I see. So this is our title slide. I'm the speaker Jack Cush from UT Southwestern, room now.

I do research for a lot of companies, including companies that make some of the products I may speak about here. I'm a consultant for these same companies. It's up to you to decide whether there's a conflict there or not. Let's begin with a definition of febrile syndromes. There's a lot of things out there, including FUO, periodic fevers, auto inflammatory disease.

Auto inflammatory disease is important consideration here because we're talking about disorders where there's inflammation that is unrelated to infection, autoantibodies and antigen specific T cell activity. It's often driven by an innate immune response and an excessive inflamisome activity. These are often monogenic disorders that begin in children and sometimes are continued throughout childhood or into adolescence and sometimes even in adults. Now, periodic fevers are often a subset of auto inflammatory syndromes. And basically they imply that fever recurs at a certain rate or interval, has a certain periodicity.

These two, because they're often auto inflammatory, are hereditary and often monogenic, although it does include some disorders which we don't have the genetic basis for, but we consider to be polygenic. Again, there should be disease free intervals and a demonstration of recurrence. Fever of unknown origin, F U O, was popularized by Petersdorf back in 1960, another report back in the early eighties. The definitions here are usually two definitions. Fever greater than 101 Fahrenheit for at least two weeks, often documented, either in the hospital or as an outpatient, and after there's been an extensive evaluation.

Again, whether or not there's a hospitalization there is sort of up to the definition, and there are two of them out there. We're gonna consider fevers. And this is a dataset that's housed in Europe. It's the in fever sort of database, and it looks at the monogenic basis of many of these periodic and auto inflammatory disorders. And we're looking at the ones that are being collected, the cases that are being collected.

This is actually about seven or eight years old, So, but it still says the same thing. What's the most common thing we're seeing? MEFV gene rearrangements, that's what you see in familial manuscripting fever. Next with MVK, that's hyper IgD syndrome. Over here, disorders of NLRP3, NLRP7, that's the inflammasome activity.

And down on the bottom, this is what you see with the TRAP syndrome. Genetic disorders involving the type one TNF receptor. These are the kinds of things that are common in the auto inflammatory spectrum and there are many, many others. In fact, there's hundreds and actually many that even haven't yet been described. But we're talking about seeing this as a consult or in a patient that you're following, these high spiking fevers and whether they remain, with an elevated baseline or they return to normal, you're being asked to evaluate that person and say what they may or may not have.

So adults do get febrile disorders. You know, lupus actually doesn't give you much high fevers. It does when you have serositis, and CNS involvement, but most lupus can give you low grade fevers. The things that are most commonly give you fever is that AOSD, adult Still's disease, PMR, GCA, and sometimes other vasculitides, notorious for presenting as FUOs, okay? Patients with the hemophagocytic syndrome or macrophage activation syndrome or whatever cause, often due to JIA, Still's disease, but sometimes due to lupus and leukemia and infection.

SWEET syndrome, Kikuchi syndrome, lymphoma, leukemia, and Crohn's, I throw in, but they're like the long tail, meaning these are very small things in the distribution of what actually happens. When you look at the things that fall under the auto inflammatory spectrum, you know, for many of them, including traps on the bottom, FMF, familial Mediterranean fever, muckle wells, about twenty to thirty percent of those patients are occurring in the adult population. More typically, an auto inflammatory disorder that typically affects adults is Schnitzler syndrome. That's a disorder that occurs in adults that is associated with a gumopathy, usually a monoclonal, sometimes polyclonal gumopathy. DITRA, which is deficiency of the IL-thirty six receptor, is typically only in adults with a psoriatic and pustular skin disease like this disorder with fevers.

Cyclic neutropenia is usually seen in adults and Still's disease, because it is a pediatric disorder with an adult continuum, occurs in about a third of the cases are, occurring in adults, usually between the ages of 16 and 35. So let's talk about this case. A 23 year old white female was presented to the hospital with a six week history of fever of 104 degrees Fahrenheit spiking every day, a rash that was on her trunk and arms and legs. She had a prodromal sore throat in the three days prior to admission. She had on presentation myalgias, wrist pain, belly pain, had a rash on her trunk and extremities.

She had previously been hospitalized between the ages of nine and 12 for FUOs, hepatitis, even called rheumatic fever at one point, but obviously no consistency of diagnosis. Now, twenty years later, she shows up in the hospital with a high fever and this constellation. And while in the hospital, she develops pleuritis, pericarditis, generalized lymphadenopathy, splenomegaly, a white count of 40,000, and increased hepatic enzymes. I don't think it's hard for you at this point to realize that this patient has Still's disease. So what is Still's disease?

When it's in the adult, it's adult onset Still's disease. And that is a systemic inflammatory disorder, which occurs in children. And then when it's in young adults, it's usually up to age 35, suggesting it is the adult continuum of the pediatric disease, systemic onset JIA. Characterized by what? Quotidian fever, zevanescent rashes, polyarthritis, not monoarthritis, not oligo poly, prodromal sore throat, serositis, organomegaly, very crazy looking labs, high high white counts with a left shift, market elevations of sed rate CRP and ferritin, and there is no diagnostic test.

Hence, this is a diagnosis of exclusion. The problem is that when this was first diagnosed in '19, or first described in 1971 by Eric Bywaters, and then re described in 'seventy two by Joseph Bujak at the NIH, the stories of these patients were horrendous. Years and years of fevers and negative workups and no known diagnoses. Now the problem is the patient gets in the hospital and on a day three or day six, the ID person says, That's not one of my diseases, call a rheumatologist, it may be Still's disease. And now you have to make an earlier diagnosis, maybe with not the full disease being played out.

The disease is characterized by the last bullet, systemic onset with intervals of exacerbations of systemic disease, with or without development of chronic arthritis, and in some people, long disease free intervals. This is a rare, rare disorder, zero point one to two cases per one hundred thousand. And if you do the math in Dallas, we expect about twenty cases in this year. If you're in a small city like Fort Collins, Colorado, it's about two cases. If you're in a big city like New York, LA, and Houston, you might be seeing twenty or thirty or forty cases in a year.

Question is, are you seeing them, the rheumatologist, and who's making the diagnosis? So, first question. Adult onset Still's disease is the same condition as systemic onset JIA, true or false? I think I kind of let the cat out of the bag on that, but it is the same disorder. If you look at the comparison of clinical features that characterize these disorders, the frequency is roughly the same.

After the first year, more than ninety percent of people are gonna have the triad of quotidian fever, the Still's rash, and the polyarthritis. The only real difference is in the prodromal sore throat, not common in kids, but very common in adults. All the other features, serositis, the association with carpal ankylosis, even the genetic associations are roughly the same. This is a disorder of males and females, and especially those 35. You can see from this graph of males and females being stacked that most of the cases here, I think this is probably about eighty plus percent of the cases, are 35 but over the age of 17.

If we had kids included in here, would be a much bigger, hump going to your left. The challenge here is that this is the leading cause of autoimmune rheumatic FUO. By all series that have been described since the Petersdorf series, the second Petersdorf series, it makes up between six and eleven percent of all cases of FUO and making it the number one rheumatic cause. The problem is that somewhere over a third of patients are gonna develop erosive inflammatory polyarthritis that looks just like RA. It does have morbidities.

This condition shouldn't kill anybody, but it could based on the high dose of steroids being used, the febrile hospitalizations, and development of macrophage activation syndrome. The diagnosis really requires the diagnostic triad of quotidian fever, evanescent rash, and polyarthritis. So this is my patient admitted to me in 1983. She came in with spiking fevers up to 105. It spiked twice a day in the first few days and had a high baseline.

And then after we put her on salicylates in high doses, she went to a once a day spike, okay, over 102. And then when she went on prednisone, can see the fever curve starts to, dissipate and reduce in its magnitude. This is very typical of someone who has adult onset Still's disease or systemic onset JIA. By the way, we will take questions at the end of this lecture. You can ask questions along by using the Q and A tab, okay?

Quotidian fevers, that means arise above 102 and return to baseline once a day. The interesting thing about Still's disease is that this Quotidian fever is a true circadian fever. They occur at the same time in every person every day. Meaning that it's usually late in the evening. It can be late in the afternoon, seldom late in the morning, never at 7AM in the morning when you have your endogenous cortisol peak between five and 7AM.

So they said 10:00, 2AM, they get the spike. Tomorrow, they're gonna get the same spike. It starts with a shaking chill, followed by this spike that goes to a 102, a 103, a 104, maybe higher. And then after a few hours, it returns back to normal. They defrovest, drench their bed clothes, often have to change the sheets in their clothes and take a shower.

The rash is called a Still's rash. It's also called a JRA rash or rheumatoid rash. Not sure why it's called a rheumatoid rash, but it is what? Evonescent, meaning it comes and goes and changes daily, maybe maximal during febrile episodes. It is a salmon pink, morbilliform maculopapular rash, maybe with areas of coalescent.

It likes the trunk, neck, and extremities, never the palms, soles, or face. It has associated features of dermatographism shown on the right, where this young, man was scratching himself. Look at his belly, he has a protuberant belly from hepatosplenomegaly. He's got dermatographism, the development of rash and kebnerization rash where he has previously scratched himself. Urticaria and pruritus is quite common in patients with Still's disease, thirty to forty percent of patients.

And urticaria is a common manifestation of many auto inflammatory disorders. This is the, again, I don't know how it looks on your screen. This is supposed to be a faint red or a pinkish kind of rash. It likes to be on the trunk. It also likes the same distribution as you might see with dermatomyositis.

You can see on the right shoulder there, the woman, this is actually one of the mothers of one of the residents that was in my program. She's been scratching herself and now she has an exaggerated wheel and flare or dermatographism. Here's a more faint picture on the chest of one of my patients. Another multiple choice question. Which is true about joint involvement in the Still's disease?

Oligoarthritis is more common. Two, sacroiliitis in twenty percent. Three, seropositivity predicts erosions. And four, more than twenty five percent develop erosive polyarthritis. Again, you should know the answer to this because I've already said it twice.

It's number four. Up to a third of patients will get an erosive polyarthritis. It looks just like rheumatoid arthritis. It can have erosions, it has the same distribution, PIPs, MCPs, wrist, elbows, shoulders, knees, and then it settles down. But the distinctive thing is that with time, those with chronic arthritis, half of them are gonna have intercarpal ankylosis, first described by Tom Metzger at the University of Pittsburgh with Wally Christie in 1976, showing a pericapitate distribution of ankylosis.

Let me show you some pictures from University of Pittsburgh. And actually, these were Gerald Rodman's patients back in 1972. LK in August shows up with high fever, serositis, crazy looking labs, and wrist pain. This is his x-ray, looks pretty normal. This is his x-ray seven months later, and he clearly has ankylosis between the capitate and the metacarpals, also between the hamate, and also over here, with the lunate.

So this is fairly typical. And while you occasionally see this in psoriatic and rheumatoid disease, it's more common in Still's disease, but psoriatic and rheumatoid disease is way more common. So think of those three, certainly think of Still's. Weight loss can be profound. When these people are really sick with their high fevers, their weight is gonna drop like this with their anemia, with their albumin.

It all goes at the same, it's a cytokine storm going on here. Prodromal sore throat in seventy percent. Myalgia is in three quarters, hepatic dysfunction in three quarters. Lymphadenopathy is seen in two thirds and then everything else, hepatosplenomegaly and serositis between twenty and forty percent of patients. These are the distinctive features.

On top right is a patient of mine with myocarditis. The same patient with a very striking chest x-ray showing pleural effusions, pneumonitis, pericarditis, pericardial effusions. He went on to have an endomyocardial biopsy showing myocardial, inflammation, but also he needed a pericardial window to treat the serositis. The labs may be as striking as the patient appears. These people look septic, their labs are notably negative for serologies.

Their white count should be high with a big left shift. They quickly develop an anemia. The albumin will drop precipitously, sed rate and CRP are up in ninety plus percent. Everybody loves ferritin, but folks, it's only elevated in fifty percent of patients. It is not as predictive as you'd like it to be.

Look on the right, this is the distribution of white count with the peak distribution being here around twenty thousand in the middle. Look at the SED rate on the bottom. Fifty percent of patients have a SED rate greater than ninety. Ninety percent of patients have a SED rate greater than fifty. That's what I came up with.

Hyperferonemia, as many times I've seen it in my career and managing patients, inpatient, outpatient, I see more of what's on the left than Still's disease, which is on the bottom. Iron overload, hemochromatosis, liver disease, neoplasia. I've seen more cases with lupus and hyperferonemia than I've seen with Still's, and I've seen a lot of patients with Still's. Nonetheless, it's a good biomarker, but it's not the best biomarker. And I think you should consider these other causes if you see ferritins of 10,000 or 5,000 or more.

On the right, you could see that it's high in active disease, it's low in inactive disease. On the bottom right shows you what happens to systemic JIA patients and their ferritin levels as they are diagnosed and treated. It will drop. Now, when I see ferritin, I'm worried about macrophage activation syndrome. I mean, and again, this is serious because it carries up to a thirty eight percent chance of death.

The number one cause of macrophage activation syndrome, if you consider all causes, is going to be systemic onset JIA with adult stills not too far behind. But it can occur in other autoimmune diseases including lupus and vasculitis, and patients who have severe infections in DB and non Hodgkin's lymphoma. They present with hepatosplenomegaly, fevers, high LFT. So far it sounds like Still's disease. But where are they different?

Well, the LFT's rise. They get scary high. They develop their high white count becomes now a low white count. They can develop DIC. They develop thrombocytopenia, leukopenia, and hyperferonemia.

These are really bad prognostic signs. The sed rate drops owing to liver dysfunction, but the CRP continues to rise. Don't miss macrophage activation syndrome. Early intervention, if they're not already on an IL-one or IL-six inhibitor, give it to them. You can get macrophage activation syndrome on IL-one or IL-six inhibitors.

Cyclosporine and etoposide have been the, preferred ways of managing cytokine storm, and treatment of the underlying disease. But now we have an FDA approved drug for the inhibition of gamma interferon. It's called Gamafant or Emipalumab. We talked about this at ACR. It's been approved for use in HLH, and you could use this in your MAS patients who have either systemic JAA or Still's disease.

It's highly effective, and you should look at the data that we've previously published on that. The diagnosis of Still's rests on criteria. Many of you, I don't know why, will call this Still's disease when you see someone with a febrile disorder, necessarily documented, and you don't know what the cause is. And well, probably Still's disease. Well, it's not that easy folks.

You either need to meet the minor and major criteria either put forth by Yamaguchi in '92, or my criteria in 2000, or even Faltrell. ILAR has criteria. I don't expect you to know these. You could look them up on the internet, but I got a website for you. It's not called RheumNow, it's called StillsNow.

And this is a spot you can go to to find lectures and videos and papers on Stills disease. And in the far right, you can see something called a diagnosis calculator. Pull this up and all you gotta do is check a bunch of boxes like this, and the website will make the calculation for you as to whether the patient, in this case this case had what? Elevated sed rate, high white count, age less than 35, daily fevers, painful swollen joints, carpal ankylosis, sore throat, splenomegaly, sounds like Still's disease, well, didn't meet my criteria, did meet Yamaguchi criteria, and did not meet the ILAR criteria. So this can be a helpful tool in managing and diagnosing patients with Still's disease.

A multiple choice question. In patients who have chronic fevers, who would you order genetic testing? Let's say it doesn't meet criteria for Still's disease. The fevers aren't spiking daily, they're kind of intermittent and maybe 101. Would you do it in patients who have a family history of fevers and similar symptoms?

Would you do it if they don't have daily fevers? Would you do it in those not meeting Yamaguchi criteria? Or I've never ordered genetic tests and don't know how to or when to. Well, would say that items number two or three might be reasonable. Throw in number one, why not?

You can do genetic testing when the diagnosis is not certain and it's not quite so hard. But why do genetic testing when you can make the diagnosis of an undiagnosed periodic fever based on the duration of the fever at presentation? So look on the far left. If the person has fever that lasts for one day or less, that's very typical for the CAPS disorder, the cryopyrinopathy called familial cold autoinflammatory syndrome. Kids exposed to air conditioning, they get fever and rashes, Guess what?

They respond well to IL-one inhibition and you can do a genetic test for that. However, let's say the fever lasts for up to three days. You might consider FMF if it's an adult, if it's not. You might also consider Mucklewell syndrome. You could treat them in maybe an empiric trial of colchicine or anakinra, or an IL-one inhibitor will tell you, or you could do gene testing for the MEFV gene for FMF, or the inflammasome genes for, McClewell syndrome.

Three to seven days is typical in kids, more so than adults, hyper IgD and FAPA syndrome, also known as Marshall syndrome. They may respond to empiric trials, or you could look for the MVK gene, the mevalonic kinase gene, which is a very common disorder, again, seen in kids. This is called the hyper IgD syndrome. If it's about two weeks of fever, seven to twenty one days, you should consider traps. The TNF receptor rearrangement that leads to periodic fevers lasting daily for up to two or three weeks.

Etanercept works here. Actually IL-one inhibitors work probably better than does etanercept. But you can also do the genetic testing. And then if they have daily fevers, you should consider SOJA, adult stills, and Schnitzler syndrome in adults. There you can do an empiric trial, there is no genetic test.

How would I get genetic testing? Well, there are a lot of gene organizations like GeneDx here, where you can order a panel from these folks. This is what we did in one of my patients, and you get back a report on either one gene that you've looked for, or you can get back a report on seven or eight genes that might be associated with common auto inflammatory disorders. This one, you order it through them or through your commercial laboratory that you're linked to, can often cost thousands of dollars and take 18 letters and four to seven weeks to get back a result. It's a hassle.

My preferred way, instead of going with one of these companies, is for you to contact invitae.com. Invitae has an auto inflammatory panel of a 107 genes. They also sell this panel for thousands and thousands of dollars. But if you make this a direct pay, where the patient can pay for this, then you can get this for, I've gotten for as little as $75 Usually the prices, you can negotiate it down to a $100. All you have to do is make the order express to the company that the patient doesn't have any money, and we need a cash pay intervention here, that they don't have insurance that's going to pay for this.

And the company will contact the patient on how to get the blood drawn, and what samples. Can see a lot of genes here, including most of the common ones that you really wanna know about. The problem here is that often we don't have a genetic cause, even in patients who clearly have an auto inflammatory syndrome that is not Still's disease, or FMF, or one of the other known conditions. John Hausman tweeted, and by the way, want to thank Richard Stern here in Dallas, who told me, who was the one who told me about invitae.com in making a genetic diagnosis. John Houseman tweeted at last year's ACR that, the NIH's, Amanda Umbrella, was doing a presentation, and she said that sixty percent of the auto inflammatory patients followed in the NIH Auto Inflammatory Clinic do not yet have a diagnosis and are therefore considered undifferentiated, meaning that there's still a lot we don't know about auto inflammatory disease.

Doesn't mean we can't do the evaluations, doesn't mean we can't make the diagnosis or even treat it. So the keys to diagnosis here is a fever has to be about 39. It has to be circadian, it has to be same time every day or every afternoon, like clockwork. I mean, patients will tell you at 10:09 or 1AM or, you know, some number very exact. The Still's rash is very helpful.

And sometimes you need to ask the patient to take a picture of that if it only comes out at night. Use the criteria, don't go by your gut, because if you use the criteria, I don't expect you to know the criteria, either mine or Yamaguchi or ILR or Fortrell's, but use the Still's disease calculator that you can get at stillsnow.com. You could try an IL-one inhibitor and see if you get a diagnostic response. That's pretty good, but realize I've seen patients who had, flu or who had lymphoma, who had their fever go away when they were given anakinra. So it is not truly diagnostic.

And then if you're not certain about the diagnosis, don't be afraid to invoke genetic testing as a tool, to manage these patients. How do you follow them? I can tell you that if they have articular disease as shown on the top left, it's just like following RA. Synovitis, TJC, SJC, RAPID three, GaAs score, CDI score, set an acute phase reactants and usual monitoring labs. But systemic disease is more difficult.

You wanna watch for the triad symptoms, fever, rash, and arthritis. But if they have other things, hepatosplenomegaly, serositis, lymphadenopathy, those are all signs of active systemic disease. Articular disease is treated just like articular disease in RA. Systemic disease, high dose steroids and cytokine inhibitors, with or without methotrexate is the way to go. Sed rate in CRP is elevated and more telltale in over ninety percent of patients with Still's.

Ferritin, while it is somewhat specific, only fifty percent. The neutrophil to lymphocyte ratio, you could look at the bottom, on the right hand side, you can see it has a very high predictive value there. And I think you should consider using that. We don't use it often enough, and it should be greater than three. If it's almost six or more, that's what you see in MAS or impending MAS patients.

Aldolase, we've treated this, just recently. Aldolase is a very good biomarker in patients who have auto inflammatory diseases, especially if they are IL-one driven. And, Aldolase, what what their CPKs are normal. It reflects hepatic activity. So draw the Alloplase, it'll be high, and usually not like, you know, 9.7 or 10.6, they'll be really high, like fifteen, twenty or 30.

And it is something that you can follow. Their CPKs will be normal. Their LFTs may not be normal. There are other things that are out there, but they're experimental, and I wouldn't recommend them at this point. If you have a patient who says they have fever, but you have no documentation, you have no chart that says that they do, go to amazon.com.

Look for these wireless smart thermometers. And this is something that you can do to monitor a baby's temperature, but you get these little pads that are sticky. You stick it under the armpit of the patient, and it it is Bluetooth connected to their cell phone, and you can get a 20 fourseven monitoring of fever. And these last, I think, for two to three weeks at a time, and they give you enough to last for six weeks. You can get a really good estimation of a person's fever before you institute expensive therapies in someone who may or may not need it.

Last multiple choice. After starting high dose steroids in someone with Still's disease, what drug would you then next use if they weren't quite controlled? Would you use methotrexate, a TNF inhibitor, number two, three, an IL-one inhibitor, four, an IL-six inhibitor, five, something else? Well, we actually did a survey of this and had over three fifty responses from you, the rheumatologist, and we showed that half of you were gonna use a biologic, and the other half were gonna use methotrexate. Of those that use biologic, three quarters believe that this is an IL-one driven disease, and therefore are more likely to use anakinra, and about a quarter believe that IL-six is what's behind this, and we're more likely to use an IL-six inhibitor like tocilizumab or ceruleumumab.

So management of systemic disease is steroids with or without methotrexate, and then either an IL-one or IL-six inhibitor, articular disease on the right, nonsteroidals, methotrexate, other DMARDs, combinations DMARDs. And then if you need to, the same thing you would do with RA. Biologics, TNF, non TNF, or JAK inhibitors, all are very reasonable. You get there a number of IL-one and IL-six inhibitors that you can choose from, and then you make the decision based on if they're doing better. There are others including JAK inhibitors, which seem to work, somewhat on gamma interferon production and interferon production in general.

Calcineurin inhibitors, cyclosporine tacrolimus have been used in some patients with systemic disease as well. I want to end by saying we have grand rounds coming up next Tuesday, all part of Tuesday night, rheumatology. Alvin Wells is gonna be talking next week about telemedicine, and what are we gonna do next? He's already done three videos for us. We're gonna get another video from Alvin.

The week after, the twenty eighth, Artie Cavnau's gonna do journal club on the Annals Rheumatic Disease article, withdrawal of low dose steroids in lupus. Doctor. Calibre is gonna talk about IL-six signaling in health and disease. On the twelfth, Joan Merrill's gonna talk about what does COVID nineteen have to do with lupus. And she's not gonna be talking about hydroxychloroquine, nonetheless an interesting talk.

Philip Robinson, one of the guys who started the Global Rheumatology Alliance in the COVID room covid.org registry, that's almost enrolled 300 patients at this point. And I would encourage you, if you have one of your patients with what looks like suspected coronavirus infection or proven, enroll them in this registry. We need that data. He's gonna talk on the nineteenth live from Queensland. And then on twenty sixth, John Kay is gonna talk to us about biosimilars and what we need to know about biosimilars.

We'll probably continue this into the June and then take a summer vacation and then resume back after the summer. I hope you found that lecture to be useful.