Double Trouble (10.23.2026) Save

Hi, everyone. It's 10/23/2026. This is the RheumNow podcast. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com.

What do you do when you find two different crystals in one joint? Should you worry about cryptococcus having a twofold higher risk with JAK inhibitors? You know there are patients out there that have myositis and scleroderma, and a Sjogren's patient who has early damage has a much greater than twofold risk of lymphoma, it's double trouble week on the RheumNow podcast. Welcome. A few FDA announcements.

The FDA has approved the new drug application for Evoxac, which is approved, as you know, as an oral pill for dry mouth of Sjogren's syndrome. The company called Cassette has been granted the right to sell oral liquid Evoxac as an alternative treatment option for those with dry mouth symptoms in Sjogren's. This is going to be available at the end of this year, it's not available right now, but I thought it was interesting. It's a new formulation of Evoxac and that might benefit a few people who have, as is often the case with Sjogren's, have a problem swallowing pills. The FDA is currently reviewing the Sun Pharma IL-twenty three inhibitor tildrakizumab.

We've seen trials on that. There have been phase three trials INSPIRE one INSPIRE two in PSA. So they're reviewing the application and the PDUFA date, the action date, is coming up next week, October 29. We'll be watching that and maybe we'll have another IL-twenty three inhibitor approved for psoriatic arthritis. It's getting crowded out there, is it not?

Many of you are using AI. I listened to a few presentations yesterday at medical schools where the overlying message was, Don't worry, doctors will always have jobs. AI will never replace you. It turns out that that may not be true, but that was the message. But doctors are needed for the empathy, and everyone was apologizing for, Don't worry, AI is here, but you'll always have a job.

You know what? AI makes you better. It makes you a much better physician. I use it all the time. I use it for organization, for step one research, and I saw this paper this week about open evidence.

I think this was published in JAMA, a study of nearly a million US clinicians, which included 560,000 MDs who submitted in a two and a half year period, submitted two seventy one million AI clinical queries in this two and a half years. MDs on average that use OpenEvents were submitting three seventy one queries a month. What? A third of it was for treatment insights, 14 was for diagnostic insights. The people who were the higher users of this AI tool, Open Evidence, were young MDs, oncologists, hematologists, internists, family medicine.

If you're not using Open Evidence, as Wendy Calabrese and I have been for a few years, I think you should be looking at it. It's a good way of... And I'll do research while I ask the same question of ChatGPT or Claw dot AI and OpenEvidence to see what they come up with. The thing about AI, well, you say, they lie, and there's that hallucination thing where it makes stuff up. If you're an expert in rheumatology, you'll spot the nonsense that AI will throw out at you.

I was in a chat ring with a bunch of my high school friends, and one guy who's very much involved with Atlanta Falcons says, hey, what happened? I heard that we lost, a game. Chat GP says that Savo High School lost, you know, 45 to 13. And I said, Chat GPT is wrong. Savo won that game.

So it does make mistakes, but it is incumbent upon you to be expert enough to spot them. Otherwise, it's going to make you much more efficient, in my opinion. A study on four eighteen patients with microscopic polyangiitis, I talked about this last week, the value in CBC information in this REVEAL study, high baseline neutrophil to lymphocyte ratio greater than 10 was associated with significantly higher disease activity measured by the Birmingham Vasculitis Activity Score, a higher risk of alveolar hemorrhage, renal dysfunction, reduced survival, and higher infection related mortalities, all from the CBC at first or baseline visit. Again, the other interesting thing about that study was a low NLR in those patients predicted a higher risk of ILD and UIP type ILD. So, again, it behooves us to figure out a way to program this information coming out of your CBC every day.

Otherwise, you've got to get your calculator out and do the math. Cryptococcus is rare. I found a study that says it's rare. It's a retrospective Trinetics analysis of RA patients who were starting either a JAK inhibitor or a TNF inhibitor. Over thirty-thirty two thousand people in each group.

And they looked at the risk of cryptococcus, JAKs versus TNF, JAKs versus non TNF, TNF versus non TNF. Turns out that crypto was seen very rarely, less than two percent, point two percent of people. That's two per thousand. I like to teach that things like cancer, TB, fungal infections are like one in a thousand, one in ten thousand at risk. I've never seen a cryptococcal infection in RA.

I have seen a cryptococcal meningitis complicate lupus, but they're rare events. In this study, they showed that there were significantly higher risk of cryptococcal infections in RA, a twofold higher risk in two different of those comparisons. And so that just means that JAKs don't have much in the way of opportunistic infections other than, as you know, shingles. That's because of its inhibition of interferon. But other than shingles, TB doesn't really happen here.

But it looks like from this analysis, and again, it's Trinetix, which is good and bad, depending on how you want to... What kind of mood you're in that day. But, yeah, you might consider that JAKs might be at increased risk for cryptococcal infections. Speaking of opportunistic infections, a Thai study looked at pediatric SLE patients. You know, they have more severe disease, do they not?

And they looked at a hundred and seventy seven pediatric SLE, thirty eight develop an opportunistic infection. Thirty eight out of one seventy seven. My goodness. That's like a sixteen, seventeen percent risk. Three point four events per one hundred patient years.

What in the world? Most common operative cystic infections were Candida twenty seven percent, Aspergillus thirteen point five percent, CMV thirteen point five percent, with skin and lung being the most likely organ systems involved with these opportunistic infections. Other risk factors included getting pulse steroids, not low dose steroids or up to ten milligrams steroids, but pulse steroids, and a SLETE I2K of greater than eleven mg, or as you would expect, disease activity would be a higher risk. Kids might be at higher risk, but kids may have more severe disease. More severe disease may bring a risk of opportunistic infections.

Two reports on gout. This report basically is making the point that patients with gout who are on allopurinol, you know what, if they have LFTs, don't worry about it. Monitor the LFTs, keep the allopurinol. One hundred and fifty patients, 56 years of age, twenty one percent on alcohol, thirty percent obese, five percent with metabolic associated steatohepatitis. And they were all on allopurinol.

Twenty percent had an increased AST or ALT. Eighty seven percent of those were mild. None of them were severe. None of them led to drug discontinuation. And again, you can continue the allopurinol without significant changes in AST and ALT.

And I think that's comforting because that's kind of what I do. Allopurinol, when LFT elevations were found, allopurinol was not deemed to be the primary cause. It was things like obesity, taking statins at the same time, etc. Another study out of Tokyo looked at one hundred and seven patients, mean age 86, and they all had synovial fluid aspiration. One hundred and seven patients.

And they all had what was the number Most of them had uric acid. I think maybe all of them had uric acid. But seventeen or sixteen percent of them had CPPD crystals also. In this cohort of one hundred and seven, there were a few people who had a history of gout and hyperuricemia, so that was seventeen out of the one hundred and seven. Half of them, forty percent of them, had a history of gouthypercemia that would explain the crystals maybe being together.

Nobody was treated for gout here. They were all treated for CPPD. Well, the good news is that the treatments are the same, are they not, for the most part? But the point is that you need to look for the crystals yourself, and identification of both could have importance as to what happens further down the road. This is a short follow-up study.

It'd be interesting to know what happens to people after two years. We did a report this week about scleroderma patients, systemic sclerosis patients who have myositis. And the cohort that we showed showed that myositis when found in systemic sclerosis was associated with an increased risk of cardiac involvement, including heart failure. Basically, those people had very little risk of ILD. Not having myositis made you have a greater risk of ILD.

Pretty interesting. Part of the double trouble story here on the podcast. An interesting study this week from JAMA about treating refractory carpal tunnel syndrome with, and I guess they just had splinting. So thirty nine patients, sixty three carpal tunnel injections, and they either had ultrasound guided hydrodissection with normal saline, no steroid. And then the second one was people who just had steroid injection, and the third group had ultrasound saline hydrodissection.

The idea is that you give the saline, it's supposed to move around the median nerve and get it to a happier spot. But they got ultrasound, saline and steroid. At week twenty four, the groups that got saline were superior to steroid alone, eighty six and ninety percent. Not much added benefit of using steroid on top of saline. Are you willing to do that?

I don't know. I'd like to see this study repeated. It's only thirty nine patients, but I think it's interesting that you may not need to use steroids. A Portuguese study looked at patients with primary Sjogren's disease and showed that early damage, as assessed by survey questionnaires, the SSDI and the SSDDi. These are things that look at what organs are involved in Sjogren's.

But if you have early organ involvement, hence damage, that they saw with those two different tools, either a 12 fold or 14 fold increased risk of lymphoma. What? Two zero eight patients, follow-up of fourteen years, damage was seen in about eighty percent of people. Mortality was linked to age, but not to damage. Lymphoma was linked to early findings of damage.

You might want to consider that. Two studies on RA, a Polish study compared the comorbidity frequency between RA and PSA. While in their cohorts, RA patients had an older age in general, and especially at diagnosis, 61 years versus 44 years for PSA, and maybe that older age could drive the higher rates of comorbidities. RA patients had significantly more comorbidities seventy four percent in RA, including hypertension, ischemic heart disease, cardiovascular disease. Comparing RA to PSA, hypertension eighteen percent to twelve percent, ischemic heart disease eleven percent versus six percent, Cerebral vascular disease, four percent versus two percent.

I've often thought that PSA, because of its association with obesity and metabolic derangement, probably had more comorbidities. But there are other studies that do point out pound for pound, RA has got more comorbidity. It's just one of the things that you're good at managing. The Italian GISEA, G I S E A, an early RA registry of thirteen oh four patients, looked at the retention rates on JAK inhibitors. Retention rates at six months, eighty one percent.

Twelve months, seventy five percent. That's pretty good. At twenty four months, uh-oh, sixty one percent. So, it's not much better than TNF inhibitors if you were to do historic comparisons. Who's not going to do well and not stay on the JAK inhibitor?

Patients who start out with glucocorticoids at baseline. Those who have high disease activity, those who have high pain scores. They're the ones who are going to bail out on the JAK inhibitor before two years. That's it for the podcast. I want to remind you, RheumNow live registration is open for the 2027 meeting.

It is January 3031 in Dallas, Texas. You can look at the agenda that's there. You can register early. There's early bird registration. We're going to have sessions on obesity, on CAR T cell, on JAK inhibitors, on lupus, I think you're going to like the program.

We'll see you there. Take care.