Seronegative RA Disease Activity (7.17.202) Save

It's 07/17/2026. This is the Room Now podcast. Hi. I'm doctor Jack Cush, executive editor of roomnow.com. I'm coming to you from the FSR meeting in Orlando, Florida Society of Rheumatology, always an excellent meeting.

I lectured here today on seropositive and seronegative RA, which one should you worry about? And tomorrow, I'm gonna be lecturing on moneyball rheumatology. I think I've I think you can find that on the podcast. So today, we're gonna talk about predicting cancer in dermatomyositis patients, saliva as home testing, and some scleroderma updates. Let's begin with genicular artery embolization, GAE.

I've talked about it before. There's been some encouraging data about its use in problematic knee OA. All the reports I've found and published on RheumNow in the last two years have been kind of positive, leading me to believe this was a potential underutilized therapy. However, there's a real reporting bias. If you look at the data and where others have looked at the data and reviewed the subject, it's kind of hit and miss.

This particular report was actually, a twelve month, sham controlled trial of GAE in painful neo A, and you know what? Pain got better in both groups but was not better with the intervention genicular artery embolization. So if I've intimated in the past that maybe this was a good idea, I think I'm recalling that. I want a do over. Some data on RA, the ARCTIC trial looked at seronegative and seropositive patients.

The ARCTIC trial was a, two thirty four patient, DMARDA naive study with less than two years of RA, where they were enrolled and followed, and they looked at different outcomes. Anyway, in this sub study, they looked at what happened to those who had seronegative RA at enrollment, and usually seronegative RA is not included in clinical trials, so that's kind of new here. Fifteen percent of their patients were seronegative, and they compared them to seropositives and what they looked like at enrollment. And this was one of the points of my lecture today. Seronegatives have more disease at the onset and at baseline, because they don't have the privilege of having a positive test to make it an easier diagnosis.

Hence, you need more disease. In this study, that was exactly the case. At enrollment, they had seronegatives, had higher swollen joint counts, 17 versus eight, higher dash 28 scores, 3.9 versus 3.4, higher ultrasound scores, 55 versus 25, and higher MD global assessments 49 versus 39, all of those being significant significant. Interestingly, no difference in HAC scores or Sharpe scores. So, but again, seronegative is, an interesting subset, especially at the outset, and they probably and there is a clear data on that they are they have a delay in diagnosis, But once they get into your hands, you have no delay in treating them, that's for certain.

International consortium from 10 European countries and almost four thousand RA patients looked at the associations of RA with major adverse cardiovascular events called MACE. This was between 1985 and 2012, twenty seven years, a total of one hundred and eighty four events. The MACE risk was really associated with disease activity, the dash 28 scores. If you had an elevated dash 28, it had an eighteen percent increase and that was significant, but it was not associated with, in this case, rheumatoid factor positivity or ACMA positivity. There are studies that do show seropositivity, especially in high titers, do increase the risk of cardiovascular events and cardiovascular death, but not in this study.

In this study, it was MACE. Other studies have suggested that the increase in cardiovascular risk with at least CCP is in fact related to disease activity. So I sort of believe this study, I think it's a well done study. Steroid use in five seventy four new newly diagnosed RA case patients. This is a review.

What do you think how many newly diagnosed RA patients are on steroids? You know, in clinical trials, the average number of patients entering clinical trial, to get into clinical trial, you have to have active disease, is about fifty, sixty percent. These are newly diagnosed. In this study, seventy five percent received steroids in the first year. Fifty five percent were on steroids at their very first visit.

Half of these people also received intra articular glucocorticoids. In this study, they did not show an association of, steroid use at low dose five to ten milligrams a day or less than ten milligrams a day, I should say, or up to ten milligrams a day, I should say, was not associated with increased risk of infection. A little bit increased, but not significantly so. A meta analysis of infection in patients with idiopathic inflammatory myopathy. I've said many times in the past when asked to talk about this, there's probably more steroid complications with inflammatory myositis than there is with systemic lupus.

Lupus, you get variable degrees of steroids. Inflammatory myositis, boom, everybody gets eighty milligrams to start with. At least that's the dose doctor Ziff taught us. That's a Ziffism, and I still think it's the right dose to start with. But because of steroids, because of immunosuppression, in this study of almost 15,000 patients, the prevalence was twenty four percent for infection.

Most of those being respiratory, including PJP, aspergillosis, and then herpes zoster being also another prevalent pathogen. Risk factors for infection with idiopathic inflammatory myopathy includes increasing age, being male, curse of being male, don't I know it, diabetes, hypertension, and having MDA five positive disease where with MDA five positive, there's a 3.4 fold increased risk and rapidly progressing lung disease part of the MDA five story. And again, once you get the lung involved, that's when you get all that pneumonia, and PJP, and that's where all the dirty stuff happens with these folks. Speaking of infection, one of the most common infections in our immunosuppressed patients is something we don't often talk about, and that is atypical mycobacterial infections, better termed nontuberculous mycobacterial infections, NTM. A retrospective study of fourteen twenty patients with, NTM infections between 2012 and 2024 showed that four point six percent of them or sixty six cases had RA.

In fifty five of those cases, NTM was diagnosed after RA. Why am I telling you this? Well, NTM can be mild, can be severe, but having RA imparts a higher risk of respiratory death, a four fold higher risk of respiratory death, and a lower five year survival, seventy five percent versus ninety three percent. Most NTM infections are not as severe or need not be as severe as TB, pulmonary TB, but they're often undiagnosed. And because they're undiagnosed, there can be morbidity and mortality associated with that.

Some of that increase in death rate and lowered survival is partly explained by A, ILD in these RA patients and systemic inflammation adding to risk. The way to prevent infection, of course, would be with vaccination. A study of the Shingrix vaccine, the recombinant zoster vaccine, in seventy six immunosuppressed systemic sclerosis patients as compared to three zero four controls. These patients all and controls all received two RZV doses. They were very high seroconversion rates.

It works. It's great. But the point of the paper was that it's not as good in scleroderma as it is in controls. It's ninety three percent versus ninety nine point seven percent. I'm sorry, that's still pretty good even for the scleroderma patients.

It's a shade lower. They had a, lower overall concentrations or antibody levels, but when they looked at cell mediated immunity, it was equal between the groups. Overall, the patients with scleroderma had lower AE events related to the use of the Shingrix vaccine, seventy four percent versus eighty six percent. Everybody gets, you know, some kind of side effects and if not just muscle soreness and whatnot. Speaking of scleroderma, a recent review looked at twenty year trends on drug use in scleroderma showing that in a cohort of six thousand five hundred and eighty three scleroderma patients followed for a twenty year period from two thousand and five to 2025, endothelin receptor antagonists and prostanoids and prostacyclin drugs, went from really not being used three percent twenty years ago to being used in twenty eight percent currently.

While calcium channel blockers and phosphodiesterase five inhibitors has remained flat, the use of cyclophosphamide has been replaced by, greater reliance on a rituximab I'm sorry, mycophenolate first and then rituximab, and now there's more use of nintedinib. Steroids, thankfully, have decreased from fifty percent down to eighteen percent, and that's a good move by you, the rheumatologist. Lastly, a, a study looked at scleroderma and malignancy risk. We've reported this before, and this is pretty much more of the same. Yes, there's a higher risk of malignancy in systemic sclerosis.

31 studies, thirty two thousand patients showed a SIR, standardized incidence ratio, where you compare the risk of malignancy in the disease state scleroderma to a population risk. That's an SIR. The SIR here is 1.66, confidence intervals 1.32 to 2.08, a 66% increase in malignancies in systemic sclerosis. Highest were esophageal cancers, liver, cervical, lung, and hematologic malignancies, including lymphoma, leukemia. Heme malignancies, the SIR rate was three point three five.

Oh, I'm sorry. All those other ones that were high actually ranged from an SIR, a three point three five, threefold, to almost fourteenfold, thirteen point nine five. The, time from scleroderma diagnosis, cancer diagnosis in this study was a mean of seven point four years. So it doesn't take forever. I did report, an update, I think it was in New England Journal, on the management of restless leg syndrome.

You know, most of your patients have a sleep problem. If you can diagnose restless leg syndrome, oh my goodness, that's so great because there are so many good therapies that you can use. You just need to diagnose it. So, and that's understanding it. This is a really good review article that you should look at.

So whether it's chronic or intermittent restless leg syndrome, the article points out that you don't need to do, a sleep study. You don't need to do polysomnography, which is an extra time and expense and a hassle to set up. But they do say as a first step, check the iron levels. RLS is associated with, iron deficiency, and you don't even need to be anemic, and then when that's present, boom, then you, basically replace it and fix the problem. You should consider removing the exacerbators of RLS alcohol being one of the prime ones.

You should recommend walking, massage, heat. Drugs that they like are carbidopalevodopa combo, pramiflexol or ropinirole, and if necessary, low potency opioids are highly effective. I like this report that came out of the FDA, it's the one hundred and twenty year anniversary and the current acting director of the FDA did a nice two page review of the history of the FDA and its role in protecting your health. It's a good overview. It starts at the turn of the century when the FDA was known as the Bureau of Chemistry.

And because of, you know, crazy sales of potions and things that were killing people, The, was a Pure Drug and Food Act, in nineteen o six. In 1930, the FDA got its name. In 1938, the Food, Drug, and Cosmetics Act expanded the role of the FDA. And of course, you know, the 1960s, the FDA was involved in denying thalidomide, and think of all that that did in protecting patient safety. When I was on the FDA advisory committees, when I went through my orientation, they recommended a book that I recommend to you.

I've read this book three times in the last twenty years. It's called Protecting America's Health. It's by Richard Hilts. I have the link on the show notes. I think you'd like that.

As you know, this is gout month. We had a lot of good count gout content this week. Great article by doctor Johnston today about the association between gout and renal disease. That's a really good read. I like this quote from Mary Wortley Montague, like people with three names.

People wish enemies people wish their enemies dead, but I do not. I say give them the gout, give them the stone. She sounds like fun, doesn't she? In 2010, colchicine fell under patent protection, and the price rose 16 fold, used to be pennies and went to like 5¢ went to $5 or more. The out of pocket cost to patients increased almost five fold.

Colchicine decreased 27% while allopurinol steroids and gout visits to the ER and to the rheumatologist all increased as a result of this legislative move. I stopped using colchicine in 2010. I barely ever use it. Now, I know many of you like it, but that's my protest. I can easily manage gout and other disorders without it.

I got a few, so don't get on me for not using it, but, I was out to make a point and I'm using it here on this platform. I liked a few reports this week, one of which I wrote, but not this one, that you can do make a diagnosis of gout by retinal scanning. There's an interesting report that using retinal scanning, just looking at photographs of the, of the fundus, high quality photographs, the study in over a 107,000 patients showed you can make diagnoses, with good certainty, receiver operating curves AUCs or diabetes of 0.83, gout 0.83, osteoporosis 0.78, hypertension zero point seven four, hyperlipidemia zero point seven four, and thyroid disease zero point six nine. Wouldn't I mean, that should be a part of every visit. You go in, your medical assistant does a, a non dilated picture of the fundus.

It gets scanned by AI. Your risks are put into your chart. It could be used as follow-up. Again, medicine is changing. You should be a part of the change.

Should you be advocating home testing for gout? You know, such a thing exists. So I wrote an article this week about saliva and uric acid testing because I read the Journal of Bio Resources and Bioproducts, had to write that down because I didn't remember it, that describes, and these are, I think, Japanese investigators that described how you can use filter paper that's, soaked in fluorescent microparticles that change color in the presence of uric acid. The darker the paper, the more the uric acid. And they can very accurately quantify this and show good correlation between serum levels.

The article talks about how you can do this at home or in in your garage almost. I don't think we're quite ready for that, But this led me to look for, home testing, via saliva. And there's there is one out there called MyFitStrip. MyFitStrip. And, I guess it's MyFit Products.

And it's basically like a urine test strip where, you put saliva on it, and again, it's got an accuracy that's probably like point eight or something like that or correlation with serums, and, it's really quite good. It's good for serial assessment and whatnot. A kit with 25 strips costs about $25, meaning you can do this at $1 a clip each time you wanna test it. Why not do it? Our last report is on spotting cancer in patients with dermatomyositis.

There was an article this week that tested the, international IMAX guidelines. We've wrote it we've talked about that before. Oroyd and colleagues presented this at ACR. It was a plenary session. I gave him a hard time about it, but I think it was a great article, a great, re report.

It's been a publication. I think it was published in 2023, where it draws a line in saying we should be doing these tests and you should test on the basis of risk. Don't do much in the way of people, for people at low risk, you do more and more people at higher risk, right? Using the IMAX guidelines, a study of four thirteen patients with known, inflammatory myositis, including clinically active, amyopathic dermatomyositis, they found that six point something percent of people had a ultimate cancer risk, that the application of these guidelines in high risk people had a yield of eight point eight percent. That was pretty good, in intermediate risk it was five point five, in low risk it was two point five.

Maybe you wanna look at those guidelines and incorporate those into your practice as to who and how you screen your myositis patients. That's it for this week on the podcast. Tune in for more. Go to the website to check out these citations and more. Check out our great gout content.

We had a fabulous Tuesday night rheumatology this week with Sarah Tedeschi, John Fitzgerald, and Nikola Dalbeth talking about urate deposition and imaging, both ultrasound and dex, and how to diagnose gout. It's a great one hour. These people are brilliant. They wouldn't let me get a word in edgewise, which is probably why you should listen to it. Next week, our webinar is gonna be equally good.

We're gonna be talking about Lisa Stamps gonna be on this one. I think Mike Pillinger is on this one and Ted Mickels. And I can't remember who the fourth person was. My apologies. We're gonna be talking about, upgrading and modernizing your approach to current urate lowering therapy.

What are you doing with allopurinol and febuxostat that actually is out of date according to the Gallup Mavens? Tune in on Tuesday night to find out. Take care.