UBER Rheumatology Ride (3.6.2026) Save

It's 03/06/2026. This is the RheumNow podcast. Hi. I'm doctor Jack Cush with RheumNow. I'm gonna be your rheumatology Uber driver.

And on this trip, we're gonna discuss some of your favorite things and a few of my favorite things on our way to your destination. By the way, where was that again? Just punch it in and, let's let autopilot take us there. And in the meantime, I'll just talk up a storm. Don't you love it when the Uber driver just won't shut up?

Well, that's what's gonna happen here. So we're gonna begin with joint hypermobility. In fact, of these first three reports, one of them is my favorite You're gonna have to figure it out. Is it joint hypermobility? Well, this was from clinical rheumatology.

They did a cross sectional study. I think this was done in Kuwait. They studied 256 young adults. I think they were all either college students, I think they were medical students. And they did, you know, Baton scores on them and tried to find out how many had hypermobility.

And then what was the incidence of other features? Well, of the 256 adults, three quarters of them were female, they found hypermobility, in forty two percent. And they based this on the Bayton scores, you know, those, like, six or eight maneuvers that you do, including elbow hyperextension, knee hyperextension, bending your thumb back, etc. And they found that of these ones who met the joint hypermobility at the lowest level, eighty eight percent had some form of musculoskeletal pain, most of that chronic, and that meaning over time, not like I don't think they really had sustained chronic. Thirty eight did have acute musculoskeletal pain and they found that musculoskeletal pain was higher in those who had Bayton scores between four and six out of a potential of nine points.

So, again, the takeaway here is it's a young person's disease. It is far more likely to occur in women. And you've got to do the maneuvers and suspect this. You know, if I'm seeing someone who I think has juvenile or adolescent, fibromyalgia, I'm doing these Baton maneuvers to see if they don't also have, hypermobility. I think it's a good idea.

I love this report from, Denmark about open access arthralgia clinics. I thought this was great. You know what, I'm going to hold that until the end because I want to talk a lot about that. My next report is on, upadacitinib, an open label trial of upadacitinib being used in Behcet's. Now, I've seen a little bit of that done, I don't know that I've ever done it.

I like managing Behcet's, I think we have some better drugs other than steroids, we don't want to use too much steroids there. Anyway, in this open label experience in '27 Behcet's patients, average age was 36 years. The, activity score was, BDCAF score was four out of a two to seven range at six months. Response was seen in eighty five percent, sixteen having complete response, seven having partial response, with substantial reductions in BDCAF scores, CRP, sed rate, steroid dose, all by week twenty four. Of that total cohort of 27, three relapsed during the follow-up period.

This is encouraging, you know? I think that, I'd like to see a controlled trial done of this because I've seen way too many people get TNF inhibitors for Behcet's, which I don't think works at all for the joint and skin manifestations. For the eye manifestations, yeah, I think it's a good data for infliximab, but honestly, I'm not a big TNF inhibitor believer there. I like to see what a JAK inhibitor would do in a clinical trial. Well designed, controlled, either active controlled or placebo controlled trial.

Please, someone should do it. A retrospective analysis of three eighty one patients with EGPA Let me say it again: three eighty one. Again, this is a pan European trial, a collective experience over a six year period from a bunch of different countries. Out of the three eighty one, they classified them as either thirty six with prodromal EGPA, two twenty with eosinophilic phase, and one hundred and twenty five with vasculitic. The point here was that half of them did receive biologics, you were more likely to get it if you had the vasculitic phase or vasculitic predominance of EGPA.

Those people had the most amount of comorbidities, they had more clinical manifestations, and they were more likely to be hospitalized. All the people, everybody was on steroids, and again, biologics were more likely to be used in those with the vasculitic stage. A report from Journal of Rheumatology looked at the IBD is there arthritis question that we have discussed in the past. Again, depends on how you're looking, right? In the past when we looked at people who routinely screened either arthritis patients, AC SpA patients, with camera studies, or bowel studies they found, you know, a fair number of occult IBD, right?

Up to ten to twenty percent. Here they're looking at fifteen fifty three IBD patients, about eighty percent looked like about eighty percent with Crohn's disease, over three hundred with ulcerative colitis. And these patients were started on either biologics for IBD or a JAK inhibitor. So they all had five years or more of symptoms, and overall, what percentage do you think developed musculoskeletal symptoms? They didn't have musculoskeletal symptoms going in, that was an exclusion.

Over time, five plus years follow-up, it's almost seven percent, six point eight percent. And one third of those, which is really only two point five percent, less than two point five percent, developed or diagnosed with ax SpA. Occult axSpA in well diagnosed IBD less common than occult IBD in well diagnosed axSpA. Predictors of developing disease was being B27 positive, where it was almost a four fold higher risk, and having higher Mayo Clinic scores for ulcerative colitis activity. About a fifty seven percent increased risk hazard ratio 1.57.

It wasn't higher with the Crohn's disease activity score, the CDAI, that was not a predictor. So why only in ulcerative colitis and not in Crohn's? Anyway, the point is that it does occur, right? Arthritis does occur, and that maybe that's the number of consults you should be getting from your GI colleagues. We know that IL-twenty three inhibitors are a big deal in IBD, what about in GCA?

We've had mixed reports about IL-17s in GCA and PMR failing in GCA in phase three trials, but showing some positive early, signals for PMR. It's still confused, we don't know. But IL-twenty three, what's the story with that? Well, here is a pilot study of fifty three GCA patients, thirty six I'm sorry, is it thirty five were given guselkumab, the IL-twenty three inhibitor, and eighteen were given placebo. At week twenty eight, no better outcomes with the IL-twenty three inhibitors.

Same amount of glucocorticoid free remissions, thirty five to forty percent, also similar flare rates, thirty one or thirty nine percent. This doesn't look favorable for IL-twenty three inhibition as a future therapy for giant cell arteritis. Diocerin. Have you heard about diocerin over the years? I mean, ever since I was a fellow I've heard about reports on diocerin, wondered why it wasn't being used in The United States or in Canada.

JAMA Internal Medicine article reported the results of DiaSerin, an oral IL-one beta inhibitor, compared to placebo in a randomized controlled trial of knee OA, but they had to have inflammation to get in, measured in a few different ways, and they had to have knee pain. So two sixty two patients, the primary endpoint was six months, almost ninety percent completed the trial, and compared to placebo no real difference in knee pain. That was the primary endpoint. They had the same amount of adverse events, forty two percent had adverse events, most of that being GI symptoms, and GI symptoms were more common with diasiran forty two percent, then placebo twenty five percent. Again, this drug is approved, this study was done in Australia, where it is approved.

It's commonly used in Southeast Asia and a few European countries. I think it's available in Mexico. Why not United States? Well, it was never developed, I think mainly because I don't think IL-one inhibition is its sole mechanism of action. And secondly, it's got a lot of GI side effects.

Diarrhea in half the patients, etc. I think those who evaluated this, and also maybe there was a patent issue, who knows? Anyway, we're not going to see that in The United States, but it is available worldwide, but it doesn't look like it works very well in osteoarthritis, hence don't do it. What about should you do in osteoarthritis? Well, you always recommend weight loss and exercise and whatnot.

Does weight loss work? Yes, we know it works. Right? Does exercise work? Uh-oh.

That's this report. Met analysis of five review studies, eight thousand six hundred patients in 28 trials show little or no proof that exercise benefits OA outcomes. In some of the studies, exercise had a small, very short term effect compared to placebo, or no treatment at all. But it was very small, very short term, almost not even worth mentioning. And again there's moderate evidence suggesting no effect on hip pain and small effects on hand OA.

Now, does this surprise you? I mean, I know you recommend exercise, but really to recommend I mean, think for exercise to work in OA, especially hip and knee OA, I think they'd have to lose weight. I think they'd have to get substantially stronger. Do most of your patients who do take your advice, who do exercise, do they really get stronger? I thought in my clinic I would post a gigantic sign out in the waiting room about, you know, the goal this year is to be strong.

That's the goal. The stronger you are, the less pain you're going to have. The more you're going to be able to move. And making that my primary message really enforces this idea of weight loss and getting stronger and exercising, because I think it's a lot of lip service. Now, were trials that were done, hopefully it was more than lip service, but this was a big disappointment.

More data about gout comes from the NHANES, a national survey that's done periodically in The United States, looked at the association of RA and gout. I don't know about you, but I've been teaching for years, yes, mostly to primary care audiences, that you can't have RA and gout, that they are the inverse of each other. And if you think it's RA and gout, well, order uric acid, order a rheumatoid factor or CCP, and the lab will decide for you, because how good are people at making a diagnosis of RA and gout if they're not rheumatologists? But if you're a rheumatologist, can say, wait, wait, wait, wait, I have seen people, and yes, I know there is. And this survey now you're relying on what patients are told and what they believe these are not backed up by chart reviews but nonetheless, according to this NHANES survey, gout prevalence is increased in RA patients compared to non RA controls.

Gout is found in ten point three percent of RA patients and less than five percent of controls, that being highly significant. Moreover, over time the risk of gout has gone up in RA patients and that RA seems to be an independent risk factor for gout with an odds ratio of two point six seven. Strongest for seronegative RA. I gotta say, there's still some confusion here. Seronegative RA could that not be gout?

How do they know it was RA? RA is stable over time, but the risk of gout in RA is increasing and trending over time. Well, isn't the odds of gout increasing over time in association with the obesity epidemic? Yeah, there's still some cloudiness here. Yes, if you're an expert rheumatologist, you can diagnose both, although I do like the idea of letting labs make up part of the decision, or letting imaging make up part of the decision, or ultrasound, if you will, because they're kind of different, are they not, by those parameters.

Nonetheless, I do think that it's worth considering that diagnosis. What else can you do in gout patients? This is a meta analysis of eight studies, two thousand six hundred gout patients shows that predictors of acute future acute gout attacks would be and you know what, they didn't put uric acid in this paper. I don't know why. But they did go on and on and on about an elevated neutrophil to lymphocyte ratio, NLR.

And the same for the platelet to lymphocyte ratio, the PLR. The NLR number should be like greater than four. I don't know what the PLR cutoff is. But if those numbers are high, your patients are probably at higher risk for future, or coming up soon, a gout attack. We're going to end with a whole lot of lupus studies and then open access.

So, prevalence of lupus in Australia. What do you think it is? The United States? I know what the Lupus Foundation says: it's five million, ninety five million, they're equating ANA positivity with lupus. That's wrong.

You know, most of the epidemiologic studies in The United States say it's somewhere between two nineteen and two ninety nine zero in The United States who have lupus. In Australia, which has one what is that? Onethirteenth the population in The United States, the prevalence of lupus is twenty six thousand seven hundred and eighty eight. Sixteen thousand it's certain, ten thousand less certain. So the incidence between twenty ten and 2022 went from seventy seven to one hundred and twenty seven per one hundred thousand and that's looking at certain diagnoses.

About half of the patients with lupus in Australia are being managed in an outpatient setting. These numbers, by the way, are on par with the same kind of incidence rates in The United States. Arthritis Care and Research had an important study this week about cause of death in lupus. It's a CDC study that looked at death certificates over a five year period where they found almost fifteen thousand SLE deaths. Forty three percent of the death certificate, lupus was the primary cause of death.

When you look at the mortality rate per million, it was six times higher in females than males almost six versus one point one in females versus one point one in males. It's over ten point it's ten point seven per million in African Americans. What are the causes of death? Heart disease was double the rate of cancer, and double the rate of COVID, and all this occurred during the COVID era, so that's why they're using that as a reference point. A lot of lupus patients must have died from COVID.

Hydroxychloroquine, a report about, from British Columbia showing that adherence to hydroxychloroquine in either RA or lupus was associated with a significantly lower risk of hospitalization. Again, you might have remembered I wrote an article, within the last four months about everybody with RA should be on hydroxychloroquine as part of a combination, because it has the same benefits in RA that it does in lupus, where we know it, you know, it lowers glucose and insulin resistance, it lowers lipids and it lowers cardiovascular events, and so on, and better for pregnancy outcomes. Again, the same thing holds true, I think, in RA, and here's more evidence of that. Other lupus news: the FDA this week granted fast track designation to Johnson and Johnson's FcRn drug, the neonatal Fc receptor blockade called nipocalimab. As you know, that's been studied in Sjogren's, it's been studied in RA.

Looked good in Sjogren's in Phase two, not so plus minus in RA. It's a positive Phase two, the Phase two JASSMIN study looked good, and now it's in a phase three trial in lupus. So again, it's a fast track for its use in lupus. It'll be interesting to see how that comes out. We also had a nice review article written by, Doctor.

Ervi Zala. Doctor. Zala is a resident at Northwestern who wrote a nice review of calcineurin inhibitors in lupus nephritis. Most of us don't use calcineurin, yet there's three out there. There's cyclosporine, Arne Cavanagh and I and Peter Lipsky were using that back in our lupus clinic at Parkland back in the late 80s in our difficult cases.

Tacrolimus is out there, and more recently FDA approved is voclosporin. As you know, the lupus nephritis guidelines talk about the use of calcineurin inhibitors. If you have stage threefour disease, that they want you to be on triple therapy, that includes steroids, mycophenolate and either belimumab or calcineurin inhibitor. But if you have pure stage five, the lupus guidelines say that you should get steroids, mycophenolate and a calcineurin inhibitor, but not if the eGFR is less than 45 per minute, meaning if they're CKD3B or worse, you probably don't want to use it because of the chance of nephro toxicity. So, these are important adjuncts that we should be using.

As you know, package insert says that the indication for use of the lone CalcinoRin inhibitor, FDA approved voclosporin, is in the treatment of adults with lupus nephritis as part of a regimen that involves an immunosuppressant. And lastly, I've a few more things. Open access, arthralgia clinics. This was a great report coming out of Denmark. And in this study they had where is my data?

A single center retrospective study of a five year experience. And what they were trying to do was facilitate referrals of arthralgia patients from primary care to rheumatologists or to the early arthritis clinic. And they inserted this in between the primary care and the early arthritis clinic to make these fast track, ten minute evaluations done by experienced rheumatologists. Over a five year period they did seven sixty one open access arthralgia clinic evaluations. And again, they just get referred with or without labs, with or without imaging, and in this five years, twenty percent of the patients were referred directly to the early arthritis clinic.

Eighty percent were discharged. Of the ones that went to the early arthritis clinic, eleven percent had inflammatory arthritis and half of them had RA. A total of thirty two new onset RA patients were diagnosed, with one in five or twenty percent of them coming from the open access arthralgia clinic. Why do I like this? I did this as a screening tool to get patients into a study.

I was trying to recruit for OA of the knee for an NIH study, the glucosamine, the gait study. And we did these basically open access arthralgia clinics. We advertised it in the paper as free arthritis clinic evaluations, diagnoses or prescriptions would be provided, meaning no they're going get a fast evaluation. And we saw in, you know, I think we did six of these, and we saw like 60 people every afternoon, and they got about a five minute evaluation. And we saw the same kind of results, except I was able to recruit, you know, like 80 or 90 people, for my OA study, but, you know, we had a bunch of people that got referred to our early arthritis clinic, or to our regular rheumatology clinic, and then we referred people to other wares for other things.

Point being that why aren't we doing this in practice? When I was teaching about the advantages of doing an early arthritis clinic, I had lots of positive responses, but nobody did it, because it really means that you would have to open up a slot and leave a slot empty for Wednesday afternoon that, your primary care people could refer to. Maybe two slots during the week, two hours each. My point was, leave them open and then you're gonna fill them because there's always people calling for appointments. And if you don't fill them, then you're going to see someone with fibromyalgia earlier than six months.

But, you know, if it's a new early RA referral, great. If it's a new onset even better! And by the way, these people are fast evaluations. You're great at pattern recognition. I think everybody should be doing this.

Congratulations to the Danish investigators who did this. A few more things. One, if you have dermatology colleagues, make sure you refer them to the Derm on RheumNow podcast. I do that monthly. It's, you can see it on the website, you can see it on YouTube, it's on our podcast channels.

It's basically a compilation of all the dermatology content for the dermatologists that I have already shared with you because you're a rheumatologist or you're room interested. Another thing: RheumNow Live is done, but if you missed it, now's the time to get it even still. You can now get RheumNow Live on demand by going to roomnow.live. It's two days of the best and most recent clinical updates with the best faculty. You can download all the materials, you can view all the slides, all the sessions.

You can listen to them or watch them, can do it whenever you want. There's pre learn downloads, there's actual lecture downloads. Again, all of it can be accessed either in the show notes or by going to roomnow.live. One more. I've been holding this one back for a few weeks because we're so busy, but I want to get to it today.

This is coming from Ask Cush, Anything from the website. You can go to the website, lower right hand corner, click on there and dictate or record your case, and I'll discuss it here on the podcast. This one comes from, Gita Fatemi. Gita is a rheumatologist in Camarillo, California, and she sent me a case that she knew I couldn't resist. It's about Still's disease.

A 42 year old thin woman diagnosed with Still's disease, it looks like twenty years ago. Onset of rash, didn't say what kind, sore throat, arthritis, fevers up to 103, hepatosplenomegaly lymphadenopathy, we said a prodromal sore throat, seronegative for RF and ANA, ferritin at times greater than 40,000, and evidence of transaminitis. You'd say, well it sounds like Still's disease. Well, she plugged it in, I said, well go back and plug it into go to stillsnow.com, put it in the Still's calculator. She said it didn't meet the Cush criteria for Still's disease, but it did meet the Yamaguchi criteria, and we all know that the Yamaguchi criteria are very good.

And you can imagine what I might say about the Cush criteria. But nonetheless, you know, this patient had, by my criteria, eight points, you need 10 points. If the patient had the classic rash, the evenescent salmon pink, rash, then she'd be at nine points. If she had the quotidian fever, that was classic, she'd have, you know, again, maybe 10 points. If the arthritis was more than one joint and it was a polyarthritis, it might have met Cush criteria.

But that's not why she's writing me. She's writing me because the patient is difficult to treat, meaning that in spite of being treated with Anakinra, Ectemra, Anakinra in double dose, Ectemra in high doses, Canakinumab, Methotrexate, Infliximab, and even a JAK inhibitor, Tofacitinib, she cannot get the patient's steroids below twenty milligrams a day. Question. So more recently the patient has been, only been able to get down to like 25 twenty milligrams of prednisone a day, while on methotrexate fifteen a week, plus canakinumab three hundred every other week, And again, they tried replacing the methotrexate with tofacitinib ten once a day or ten, twice a day, still unable to wean the steroids. And anyway, my answers back to Geeta was, one) Does it meet the criteria?

Two) When you encounter what you think is difficult to treat, Still's disease, my first go to is to call someone who treats a lot of Still's disease. By the way, that includes the pediatric rheumatologists who are way better at this than we adults, because they see it all the time. Pediatric Still's is the same disease as adult Still's. Or call in your community rheumatologist that you know see a lot of Still's. Or if you don't know, call me, or send me an email like Geeta did and I'll always respond back to you or present it here on the podcast.

But when you get difficult to treat Still's disease, and they're really not behaving, as they should when you use your strongest drugs, then the first thing I do is genetic testing. Meaning, I'm going to send off a panel of genes that look for auto inflammatory conditions. So, I said to Geeta, in my clinic, and I've seen hundreds of referrals from rheumatologists from all over the country, all over the world. And of all the referrals I've ever gotten, and these coming from very smart, great rheumatologists like yourself, only forty percent have Still's disease by criteria, by my criteria, or Yamaguchi. But I don't feel bad about that, because if I were working with Raffaella Golbakmanski and Dan Kastner in their auto inflammatory clinic at the NIH, we would know that only sixty percent of our auto inflammatory patients have a defined diagnosis, and there's forty percent that we're just not going to know, but we're going to manage them.

So, get a gene panel, maybe you get another insight as to what this could algorithm here begins with: are you treating systemic disease or are you treating arthritis? If you're treating arthritis with stills, then treat it as if it's RA. Are you treating systemic disease? And by that I mean high fevers, irresistance, high white counts, very high sed rates and CRP. I don't hang my hat on ferritin only fifty percent of patients have an elevated ferritin, and only ten percent have that hyperferritinemia that you all think is so pathognomonic when it really isn't.

But it's great if I see hyperferonemia, I'm worried about MAS. And yes, Still's is a cause of MAS. So, are you treating systemic disease? And if you do, European and PRINTO guidelines and ACR guidelines say use an IL-one inhibitor or IL-six inhibitor first. And that steroids, you know, aren't the first line therapy, Okay?

And in my experience, again, it's IL-one or IL-six often in high doses, right? Maybe higher than what you're prepared to use. Not a hundred, once a day of anakinra, but maybe a hundred twice a day, or two hundred QHS because IL-one is secreted at night when they're asleep. Same thing with IL-six, the tender trial, use doses, and this is in kids, with systemic GIA, use doses up to twelve milligrams per kilogram, and you're playing around with four, or maybe eight. Again, wouldn't want to be on twelve for a long period of time, but at least to get control of disease.

And then I like using JAK inhibitors, but we need to see clinical trials of JAK inhibitors. My experience has been positive and everybody's probably on a background of methotrexate if they have problematic disease. I wrote down to Geeta, I don't think there's any value in trying for systemic disease, trying rituximab, abatacap, colchicine, or even more steroids. For me the jury's out about adjunctive use of azathioprine, hydroxychloroquine or a calcineurin inhibitor. Anyway, you got a case?

Go to the website bottom left hand corner. Click on Ask Cush Anything and, we'll discuss your case in the future here on the podcast. Oh, we've arrived at your destination. The bill is, as shown on the meter. Take care.