Doubting RS3PE (8.14.2026) Save

Hello, everyone. It's 08/14/2026. This is the Room Now podcast, and I'm doctor Jack Cush, executive editor of roomnow.com. This week on the podcast, cancer, deadly viruses, AI, more AI rules, but there's gonna be some poetry and good moon rising. Let's begin with numbers in medicine.

A report this week in JAMA talked about the number of internal medicine doctors that have dropped in The United States. I think the purpose of the article was to point out the consequences of recent immigration policies which are hurting healthcare. They looked at the twenty twenty six PGY one match rates and, showed that the number of non US citizens who are international medical graduates has reached a five year low, but say what you will, think what you might, the fact is that international medical graduates, in most instances, make up as much as a third of our healthcare delivery. We need them as much as they need us. Buried in there were some interesting numbers for rheumatologists.

It's always a bit of a puzzle as to how many rheumatologists are there in The United States. The ACR has numbers. They recently crested over 6,000 in their last release. In this report that looked at, I guess NPI and Medicare numbers, the number of rheumatologists in The United States is six thousand three hundred. How many of those are born locally or born internationally or where were they trained?

The greatest majority, 47% were US born, US trained, physicians. The next biggest lot is 37% were foreign born, foreign trained physicians. I am a US born international medical graduate. I graduated from St. George's University in Grenada.

We only make up 5% of the rheumatology workforce, and then non US born, foreign born, but trained in The United States is 11%. I think you belong to one of those groups. We all belong to the same group, the great group of rheumatologists. A biomarker sub study of the Senesse study, which as you know is a Nintedinib trial used for registration, of Nintedinib, for patients with scleroderma ILD, This looked at the biomarker studies that they did. They looked at a number of different things.

The two things that stood out in this sub study was the biomarker that's used all the time in pulmonary medicine, KL6, and is that KL6 or KL5? You look it up. Levels greater than a thousand at baseline was associated with greater risk and worsening of FVC, meaning you're at a greater, a higher risk category, you're more likely to progress and progress more rapidly. The other interesting thing I didn't know about was CA125 used in other cancer, as a cancer biomarker showed that that was associated, a decrease in CA125 as a result of treatment especially was associated with better responses to the study drug, which was entedinib. We do know that CA125 is produced in the lung.

You may want to consider doing these biomarkers in your patients in whom you worry about ILD, and I don't think it just applies only to scleroderma associated ILD. The Japanese put out a study this week looking at five predictive factors for cancer associated myositis. They had a cohort of three sixty four patients with meeting IIM criteria. Eleven percent of them or forty two had cancer associated myositis abbreviated CAM. Thirty of the forty two were diagnosed within one year of the diagnosis of myositis.

And generally, it's been said that the risk of cancer is three years around the diagnosis, plus or minus before or after a myositis diagnosis. But they showed in their study that the risk is highest in the first year, SIR of eight point six, and it's still high, at three years at two point five. The point of the study was how can you predict? There were five predictive factors: TIF1 gamma, elevated CRP, dermatomyositis, older age and a positive family history of cancer. Using those five, the AUC was 0.86, sensitivity 92.5, and specificity 65.

These are pretty good. As you know, we talked about the IMAX, risk stratification, I think two or three podcasts ago. I think this sort of complements that, especially who might be at high risk, and I like that, you know, these can easily be employed into practice, but I do want to say of those five factors, there's a disproportionate dominance of TIF1 gamma. TIF1 gamma antibodies was, if you look at the bar graph, was way out there to the right compared to everything else. So, again, myositis associated testing for antibodies, I think, is indicated, especially in older patients, especially in dermatomyositis.

Speaking of odd tests, anti coo antibodies. The good news is I can spell it, k u. The bad news is I've never ordered it because I've never seen the point, but the point of this paper was a study of a 154 anti coo antibody positive individuals showed some interesting data. First off, they were seen, one third of them were from myositis patients, and it is a myositis associated antibody. It is not a myositis specific antibody.

Right? But forty six had lupus, thirty had Sjogren's, and twenty seven had scleroderma. Thirty nine percent of these coo positive patients had ILD and those people with coo were more likely to progress. Seventy five percent of them had progression of their ILD, especially in males. So, could CU antibody regardless of diagnosis be a marker for ILD that maybe you should order and be unlike me?

And I was about to write that because that was a takeaway of the paper, and then I started, you know, playing on open evidence and looking for what's the story on coo, but coo is rare rare rare. Even in myositis, it's less than four percent. You know, it's one to four percent. It's not specific as this paper says. It's seen in almost as many people with lupus as there is with myositis.

It doesn't have clear clinical implications, although that's what this paper would want you to believe And then there are other myositis associated antibodies that you don't often order in myositis like row fifty two, row sixty, u one RNP, and PM slash SCL, another test I've never ordered. Maybe it got ordered inadvertently. The point is, this is interesting data, I don't think it's gonna change my practice. What do you think? The CDC put out a report this week.

Actually, my editor, found a report on Medscape, which references the CDC release this week, saying that patients treated with anti CD20 monoclonal antibodies are at a higher risk for severe arboviral disorders, arboviral infections, especially that affect the neurologic system and that there are, is a forty percent risk of death, there's a high risk of serious neurologic sequelae, and we use anti CD20, do we not? Rituximab, ocrelizumab, ofatumumab, obentuzumab, just recently approved, these are in that category. Now, what I don't like about well, first off, the most common arboviral infection noted was West West Nile virus. The other ones were so uncommon, they don't even list them, but there are a number of, you know, Eastern Equine, encephalitis virus, you don't do that, but, you know, arboviruses are alpha viruses. I think that includes the viruses that cause chikungunya and Zika and other things.

And we do know that B cell inhibition, especially monoclonal antibody B cell inhibition, is associated with more viral infections including herpes zoster, right? Rituximab is associated with, PJP infection. Well, that's not a virus, that's a fungus, but, the point is that if you're going to use B cell inhibition, there is a risk of serious infection, some of which may not be overt bacterial infections. So, you wanna be aware of this, and watch for this. The other thing about that CDC report, they don't give any numbers.

You know, tell me this was for three thousand people in Wisconsin and I'd be worried, but there are no numbers and there's no numbers on mortality rates or hospitalization rates. Maybe that'll get flushed out in the future, but this point, it's just a warning that's designed to scare rather than instruct. And, of course, I'm reporting it. I'm part of the problem. A study this week of glucocorticoids and depression.

You know, I don't know about you, but when I prescribe, when I prescribe steroids in my patients, my objective is primarily to treat the patient and what's urgent that's so much so they need a steroid. My other very close second objective is to scare the hell out of them about steroids. I'm gonna give you this drug. It's gonna make you feel wonderful. Steroids are the best drug and the worst drug.

Worst drug, what do you mean? Yes, if you stay on steroids, you're gonna get fat, you're gonna get ugly, you're gonna get hypertensive, you're gonna get diabetic, you're gonna get cataracts, you're gonna have muscle weakness, you're gonna get stretch marks, you're gonna have a higher risk of infections, and I mean, mild infections, serious infections, hospitalisable infections, kill you infections, and you'll have a higher death rate. And then, of course, the patient at this point is like, woah, woah, woah, Cush, what are you doing to me? Well, that's what I've done. I've now motivated them to get off of steroids.

Well, this interesting study and we always talk about the CNS side effects of steroids. I think we talk about steroid psychosis a little too much. I rarely I maybe have seen one really good steroid psychosis. It does play games with the head. Mania is way more common.

If you have an underlying, you know, psychiatric problem, psychological problem, that'll get worse. But is there an association with depression? And clearly, I think there is. This UK clinical practice research database study of thirty one hundred people on steroids who were thirty one hundred who have depression in that large UK database, thirty one hundred of them were on steroids. They matched them against other patients who were not on steroids.

So glucocorticoid use was associated with a significantly higher risk of starting a SSRI antidepressant drug. That's kinda interesting. Sort of fortifies the association. This applies to starting a recent glucocorticoid where the odds went up fifty three percent or previously or in the past, you've been on glucocorticoid where the odds go up forty percent. Those are significant.

So, is this depression that's linked to the disease, having pain and severe disease and chronic disease gives you more depression, or is this depression linked to and therapy for depression linked to the use of the glucocorticoid. Yes and yes, and yes, we should be worried about depression in our patients. Another study, from NHANES, looked at the prevalence of, arthritis in adults who have depression. So these are, fifteen thousand depressed patients with a PHQ-nine score of greater than 10. Of those people that had arthritis, RA was most prevalent and when they looked at this, NHANES from 2005 to 2018, the thirteen year period, the RA prevalence went up in depressed patients from seven point eight percent to almost eighteen percent.

Interestingly, psoriatic arthritis, unknown association with depression, declined from seven point two to one point seven and OA remained unchanged about ten or eleven percent over this span having, depression if they had OA. So, in the end, the risk of depression was highest with RA, forty percent higher, forty four percent higher with psoriatic arthritis. So, that associated psoriatic arthritis is real, but maybe the heightened awareness of that has led to better treatment or I'm not sure exactly what but I like that the numbers did go down. Again, PHQ-nine was the identifier in this study. There's a PHQ-two, these are either nine question, survey question, test or a two question PHQ-two that you can incorporate into your survey or in your patient intake so that you can identify patients who have depression and then manage that.

Pollution was in the news. A Korean study showed that RA activity, and flares is increased by pollution. A thousand patients, I think it was on PLOS1, were assessed for disease activity in their RA and they looked at pollutants that were prevalent in the era and the location of the patient. We're talking about sulfur dioxide, nitrous oxide, ozone, carbon monoxide, particulate matter 10, that's 10 microns or up to 10 microns or particulate matter 2.5, PM 2.5. So, these pollutants, PM 2.5 have the most greatest risk of flare, eleven percent increased risk of flare if they're exposed to particulate matter, and also increases in dash 28 CRP, Cdye, TJC, and SJC.

This was seen more so in women who were non smokers. So, again, made that, one of my, program lectures in past RheumNow Live lectures you know, it's a really hot topic, think. Environmental rheumatology, what are the things that surround us besides diet, which affects microbiome, and smoking, which affects the lungs, and pollution, you know, and probably there are others that we are not yet focusing on because these become modifiable risk factors, do they not? Did I mention RheumNow Live? Oh, yeah, it's coming.

January thirty and thirty first in Dallas, a day and a half meeting, the best meeting in rheumatology, the most interactive meeting in rheumatology. You can register now for RheumNow live. The POETIC PSA one study, it's also sometimes called the POET study because no one can pronounce poetic which ends with a t y k. This was the registration trial that got ducravacitinib approved. It's a trial in biologic naive PSA patients with active disease, six seventy patients who are randomized to receive ducravacitinib, a selective, oral TYK2 inhibitor, and the pay in PSA and patients, did really very well with ACR twenty, ACR 50, ACR 70, and, other measures as well.

The ACR twenty response was fifty four percent versus a 34% placebo response, a delta of 20% that is significant in this day and age, and that higher placebo response is significant in this day and age for reasons that we've already discussed. Again, these were biologic naive RA patients who had erosive disease. The other readout on this was radiographic benefit and ducravacitinib, a TYK2 inhibitor was shown to retard X-ray progression in these patients both at week sixteen, very early, and at the, at the longer endpoint week fifty two. Good data finally published, we talked about it for almost two years on RheumNow. New data coming from Moon Lake, that's a good moon reference right there, and they announced their phase three data of their IZAR-one studies.

It's a randomized controlled trial of sonolizumab. Sonolizumab, their dual, IL-17AF inhibitor that's not yet approved for CPSA, but this trial showed significant responses at week sixteen. An ACR 20 of sixty six percent, an ACR 50 of forty two percent, an MDA of forty one percent, a PSA ninety of sixty one percent. These are all very favorable data. There is a phase two ISAR two trial that's in progress.

I would expect to see another dual AF inhibitor on the market sometime in the future. A sub study of 131 patients from the ADA registry, that's the auto inflammatory disease, registry, looked at responses to canakinumab and in that one hundred and thirty one patients with Still's disease, kids and adults, thirty eight percent were underdosed according to package insert. Sixty two percent were appropriately dosed, and not surprisingly, the underdosed patients had a lower odds of achieving remission or being able to achieve or discontinue canakinumab in the future. Discontinuation of canakinumab meaning that they went into remission, you no longer need the drug. So discontinuation was three point nine percent overall in the under dose and nineteen percent in those that were appropriately dosed.

I want to remind you if you're treating Still's disease, you may have a dose in mind for an IL-six inhibitor or an IL-one inhibitor, but look up the data or look up what I've said about this in the past. Sometimes you need more than the usual dose. A hundred milligrams of anakinra may not be enough. Three hundred milligrams of canakininab may not be enough. Four to eight milligrams per kilogram of Actemra tocilizumab is definitely not enough.

In the tender trials for systemic JIA, they used up to twelve milligrams per kilogram. The point is at the outset when they're red hot in the hospital, in the ICU, crazy scary labs, don't be afraid to go a little high, get control of the disease, have some background steroid and then wean down the therapy. Speaking of scary diseases, Kawasaki disease report becomes instructive this week from, Japan looking at the incidence of Kawasaki from 1975 to 2025, a 16 fold increase. Woah. And in 2023 and 2024, they roughly had fourteen about fifteen thousand cases annually of Kawasaki's disease in Japan.

But a big part of this report was that the number of Kawasaki patients dropped significantly during COVID. And even after COVID, it was still ten thousand in 2022. It was much lower in 2020, 2021, but it rebounded post COVID when all the restrictions on kid exposure from masking to being out of school, etcetera. Infants and infant rates did not change during COVID, but kids five to nine, school age kids showed the greatest increase. All the point being here that that this is probably a communicable, infection related or airborne related phenomenon or at least in part is, and this should help researchers who are working on this.

We put up a report from JAMA this week with updated guidance and these are JAMA rules on the use of AI. They cite that despite increasing use of AI in society by everyone, including you, me, and your mother who still doesn't know how to operate an a VCR, who has a VCR, In the journal world, the medical literature world, AI disclosure is rarely noted in the methods or in the paper. There's a bit of a problem here. You know, we note it in RheumNow, as a checkbox that and I use and my team uses a lot of AI. We use AI for, research, organization, first drafts.

It's all but then we disclose it and that's something you'll see that when you look at the disclosures on things that I write or appear in RheumNow. Here are the rules, the new rules for, AI on JAMA. AI must not be used to generate references. If you've ever looked at references generated by AI, it's funny. They're not even close.

Do references the right way. AI cannot be used and should not be used to generate opinion articles, letters to the editor, or online comments. How lazy are you? You're not even writing a real a real full length paper. You're writing a letter to the editor and you're using AI?

Come on. Clinical images, illustrations, and AI generated video or audio should not be used unless it's necessary for the kind of research you're doing. Disclosure is mandatory and must be placed in the acknowledgments, if not other areas, but at least in the acknowledgments and methods sections and the other one that really I found surprising and new is people using AI to review articles. So, I get invited by the Journal of Irreproducible Results to, review an article that I wrote anonymously on Still's disease and it gets sense to me to review it, but I'm too lazy. I take the article and put it into Claude or Gemini or Copilot or ChatGP nine and really?

People are doing that? Again, it's lazy. It's prohibited. Okay? If they catch you doing it, they're gonna hang you up by your thumbs.

Two more reports, the ZEUS trial is a cardiology trial. It's got nothing to do with rheumatology but it's got everything to do with the concept that the cardiologists have been playing with that inhibition of inflammation will lead to better cardiovascular outcomes. So, have, an IL-six inhibitor, ziltavecumab, ziltavecumab, and they did a phase three trial of over six thousand patients who were high risk. They had atherosclerotic cardiovascular disease, and CKD and an elevated high, sensitivity CRP. Hence, the population was enriched for people who would likely have an elevated CRP and likely benefit from IL-six inhibition, right?

And guess what? IL-six inhibition dramatically lowered IL-six levels and lowered CRP levels, but didn't change cardiovascular outcomes. All cause mortality did not improve, hazard ratio 0.99, even in a highly enriched population. There was no change in MI, stroke, or cardiovascular death. Now, follows on the heels of other well known trials, the CERT trial with methotrexate, the CANTOS trial with canakinumab and IL-one inhibition, two colchicine trials that basically have shown that, well, the colchicine trials did show benefit, but the IL-one and the IL-six inhibition trials did not show benefit, Cantos and Sert and methotrexate.

So, again, I think this is data that you need to know about. It's great maybe to lower acute phase reactants in heart failure, but they're going to have to do other things and do the things that they typically do. An article written this week by Lee and Macris, and coworkers, was a review article from late June in JAMA on evaluating inflammatory joint pain in older adults. Really popular, got tons of reads. The takeaways here are that there's a significant diagnostic delay in the elderly that should not happen, but it may happen because of atypical presentations or symptoms being ascribed to, oh, you're just old, it's aging, get over it, or problems with labs.

They want you to say that a lot of the they want you to know that seronegative RA can mimic PMR and vice versa, and that you can distinguish between the two based on, hand and risk synovitis and elevated inflammatory markers and, dysfunction favors RA over PMR. They want you to think about mimics here that could be misdiagnosed, including CPPD, inflammatory OA, and RS3PE. Let me come back to that in a second. There is a lot of suspect and worry and inaccuracy about laboratory testing in the elderly. They have a threefold higher rate of autoantibodies, ANA and, rheumatoid factor and CCP.

SED rate and CRP are falsely elevated by age, especially, SED rate where the formula is your SED rate upper limit should be, the SED rate divided by two if you're male, If you're female, it's your I'm sorry. So your age divided by two if you're male. Female, your age plus 10 divided by two. So an 80 year old woman, plus 10, that's 90, the upper limit is 45, so that's not elevated for an 80 year old woman, and they're, you know, they want you to use other diagnostic tests like ultrasound, not just radiography, especially if you are suspecting, this. Lastly, the big point is the elderly are undertreated when it comes to DMARDs.

Age should not be a contraindication of methotrexate use, or biologic use, but yet all studies show it is you seem to have a hesitancy because maybe they have comorbidities. Well, comorbidities are prevalent all the time and not just restricted to age. Let me say something about RS3PE. I have never seen one. I joked about this back when Dan McCarty wrote about it during my fellowship.

Not that I was joking about Jan McCarty, a giant, I worshiped the ground he walked on, but he described this, seronegative symmetric synovitis with pitting edema RS3PE as a unique syndrome, possibly crystal related, but honestly, nobody knows what it is. I don't think you've ever seen it. I think if you follow them long enough, they become something else. There is no epidemiology on this. I did some research because I want to fortify my being a curmudgeon on this.

There are no numbers on this. Even with the most rare disorders, I can give you the exact epidemiology on Still's disease. There are no numbers on this, but it's rare. They don't even say it's very rare. If I've never seen it, it's very, very rare, and hence, I'm not even, sure that I know what it is except in this article, they say if you diagnose RS3PE, recent reports suggest that you should be thinking about an occult malignancy.

So we don't know the cause. It could be something, some crazy variant of RA, which is probably 39 disorders, not one, seropositive, seronegative. You should it's been described with, immune checkpoint inhibitor related, adverse events. It's got linkage to HLA B27 and HLA A2. So, despite my protestations, there's still a science here that's unresolved.

I don't know. I just want to be a good rheumatologist. So, let me end with that. A great quote, one of my favorite quotes from the comedian Steve Martin as he was coming up in the business said, be so good they can't ignore you. I like that.

Be so good they can't ignore you. It means there are no shortcuts to greatness. It means that be so good that they can't ignore you. That applies to your career, your family, your people you work with, your group, and why not your patients? Be so good with your patients that they have to say, oh, yeah, I have the best rheumatologist in the whole world.

God bless you and God bless rheumatologists.