How Does Your Garden Grow (9.26.2025) Save

It's the 09/26/2025. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. It's the end of the summer.

I hope you've enjoyed it. It still may be good enough to go out back. Look at that pool. You know? You could exercise.

You could qualify as hydrotherapy. But, you know, if you don't have a pool, you got a garden. Look at the garden. Look at those tulips. Oh my goodness.

You know? But what if you have fibrosis in your garden? How does your garden grow? We're going to discuss these existential issues in this week's podcast. First, lupus.

A nice study from Australia looked at the relative frequency of autoimmune disease. This is a meta analysis, I think it was, of 47 studies looking at incidence and prevalence rates in Australia for, a number of different conditions of concern to you. Leading the list is lupus at fifty seven point nine per hundred thousand, people, and I think that's important to note, because now we can compare other disorders to lupus. So lupus nephritis, it's eleven point two per hundred k. That means about one in six lupus patients may develop should develop lupus nephritis.

Scleroderma, not as high as lupus, but higher than lupus nephritis. I was surprised at twenty five or twenty six per hundred k. ANCA associated vasculitis is about the same incidence as lupus nephritis as is inflammatory idiopathic myositis, roughly around ten, per hundred thousand. So anyway, interesting relative comparison of frequencies looking at prevalence rates in Australia that I think it's instructive. I like this study about comorbidities in, lupus and asked the question, should we be scoring comorbidities using the Charlson Comorbidity Index?

In my patient visits, I got a questionnaire and it asks for comorbidities that patients can check, and I can do an informal Charlson Comorbidity Index. This Japanese study did a meta analysis of three studies of 100 and not 100, 1,100, SLE patients and showed that having a high CCI or comorbidity index was associated with worse outcomes. It predicted all cause mortality, and overall just worse disease. If you had a, it could be as high as fourfold higher, mortality rates based on the Charlson comorbidity index. You know, this has been shown for RA.

I assume it would apply to other disorders. It wouldn't hurt for you to do an informal comorbidity index in patients that you're treating, meaning that you see multiple comorbidities. Uh-oh. This is now a new category of disease. Yes, you should be aggressive.

An interesting study from Canada and the University of Toronto looked at whether antimalarial exposure, affected the risk of lupus nephritis. So it's an inception cohort study of, almost seven hundred patients who did not have lupus nephritis. They were 34 years of age at baseline, twenty three percent developed lupus nephritis on median a follow-up of three and a half years. Overall, antimalarials did not lower the risk of future lupus nephritis. The hazard ratio is 0.98, and it was the same if you look at those who had serologically active SLE and whether or not they received hydroxychloroquine.

This is a little, in conflict with other data that's out there. The data that being on hydroxychloroquine prevents lupus nephritis, I don't think it's so clear and this further muddies it up and says maybe it doesn't. The data on whether if you have lupus nephritis and you're on hydroxychloroquine, that seems to be clear that it does improve all outcomes if you have lupus nephritis. So it depends on which way you look at this particular problem. Of course, we know everybody with lupus should be on hydroxychloroquine for its many benefits, diabetes, lipids, antithrombotic effect, pregnancy benefits, etcetera.

What about, the time it takes for derm to send you the psoriasis patient and is this psoriatic arthritis? A study from Turkey looked at almost eight hundred patients with psoriasis and looked at the interval it took for them to not be referred, but to be diagnosed. So thirty percent of their patients had a concurrent onset of both psoriasis and psoriatic arthritis, I think the window was within a year of diagnosis, thirty percent. That means seventy percent there's going to be this delay. And we've often talked about the delay being, you know, seven to fifteen years or whatever.

In their study, seventy percent had a long transition time, they called it, of around thirteen years, and factors that were associated with prolonged transition to psoriatic arthritis included depression, fatigue, scalp psoriasis, nail psoriasis. Scalp psoriasis, sevenfold higher odds, of progressing or transitioning. Nail psoriasis, threefold higher odds. And then having a positive family history of psoriasis or enthesitis anywhere gave you a twofold higher risk. If you had a positive family history of psoriatic arthritis and you had psoriasis, it was much higher risk of progressing to psoriatic arthritis.

Pretty cool study. Thank you, Turkey. Canakinumab, how do you treat it? I'm sorry. Vexis, how do you treat it?

And this report is on the efficacy of IL-one inhibition, especially canakinumab. You know, Vexis can be treated with drugs for myelodysplasia, JAK inhibitors, biologics. I'm not really clear about what's the best therapy. In this one small cohort study of forty seven males who had Vexis, forty four were treated with anakinra, nine were treated with, canakinumab, and six were treated with both. And the efficacy between anakinra and canakinumab, anakinra loses, canakinumab wins.

Response at one month, thirty four percent for anakinra, a hundred percent for canakinumab, response at three months, twenty two percent anakinra, seventy eight percent for Canakinumab. Drug survival is fifty four months with Canakinumab and only, that's Canakinumab three hundred milligrams once a month. It was only seven months at one hundred fifty once a month. So it looks like you need the higher dose. It's only one month with anakinra.

I think that if you're gonna go and you can use IL-six inhibitors, TNF inhibitors. I don't think I don't I'm not impressed by that. But if you're gonna use an IL-one inhibitor, I think canakinumab is going to win over anakinra, and the higher dose should be the advised dose. A study from the arthritis power group looked at the incidence of non serious infections in RA. This is a registry.

They looked at three fifty one patients and their survey reporting of what happened to them. Thirty one percent of their patients overall had non serious infections, the most common being upper respiratory infections. Very, very, very few of these resulted in emergency room visits or hospitalizations, but they did by getting this NSIE, non serious infectious event, they were more likely to miss work, have drug interruptions in a quarter of patients and more fatigue. And then there was a trend towards more disease flares, because of missing work and drug interruptions that qualifying as a flare. I've always been very interested in this because half of our patients are going to have NSIEs and it complicates therapy.

I say never stop a biologic or advanced therapy for the sniffles, cold, the UTI. No, it's never happened in the clinical trials. It should not happen in practice. Moreover, there's no data and I've tried to get this data, but couldn't get cooperation from companies to look at this. People who developed NSIEs, URIs, UTIs, etcetera, did they go on to develop serious effects events, hospitalized for that problem or get a pneumonia?

Or if they had repeated NSIEs, did they have more serious? And the answer is, in my opinion, no, but there's not good data on this, but maybe this report kind of hints to what I've been saying all along. Primary CNS angitis, not something often seen, a retrospective study of forty nine patients looked at correlations of vessel size to outcomes. So patients were diagnosed by imaging and by neuroradiologists and with the overall picture that came out of this was that small vessel involvement was the bad kind, meaning nine out of the forty nine had small vessel involvement. They were more likely to have positive brain biopsies.

They were more likely to get cytotoxin, have functional decline, and have more relapses of their disease. So finding a specific vessel size, especially small vessel disease, that is helpful and can tell you maybe where you should be going, how much you should be worried. A very simple study was came from PLOS, this this year, this week. This is a study of medical interventions in knee OA. So it's a systematic review of 139 clinical trials, and looked at 12 non medicinal treatment options for knee OA.

This included laser therapy, TENS, diathermy, electricity, I don't know what that means. Ultrasound, lateral wedge insoles, knee braces, exercise hydrotherapy. Yeah. Get out in the pool. Kinesio taping, extracorporeal shockwave therapy.

Really? Well, anyway, they showed that the simple things probably work best. For pain and function in NEO A, the knee brace was the best followed by exercise and an ultrasound was worse. For overall Womack improvement, which is the standard, outcome measure in OA trials, best was hydrotherapy, then exercise, then laser therapy, interestingly. Shortwave diathermy was worst.

So this these would be adjunctive measures that you would be using in addition to what you're doing medicinally or surgically. Retroperitoneal fibrosis. Have you ever seen one? Have you ever I've tried a diagnosis maybe two or three times in my career. I've never diagnosed one, never seen one.

Makes me think I've probably missed a few. I'm gonna guess that you haven't. But the question is, what's the therapy that you should use? An open label study of sixty patients with newly diagnosed idiopathic retroperitoneal fibrosis, with, a GFR, meaning a kidney, disease not being too bad, greater than 30 cc's per, per minute. They were treated with low dose methotrexate and prednisone versus prednisone alone.

What's the outcomes? At nine months, remission was seen in ninety percent on methotrexate prednisone and eighty one percent on prednisone. You could say this was probably non inferior, although this was not a non inferiority trial, this is just a report. The time to remission, was also better, in the same way as was thickness of the fibrosis. So maybe the one thing that was better was that prednisone use was overall lower when methotrexate was being used and that was significant.

So methotrexate prednisone, who knew? I hope you're diagnosing it. I certainly have missed opportunity. Scandinavian Journal of Rheumatology asked the question, how are we doing at screening for, interstitial lung disease? I'll remind you, September is ILD month.

We have a campaign on ILD, lots of great content on ILD. Hopefully, you're enjoying that. We've had great Tuesday night rheumatology meetings, including a great journal club last week that featured Sherwin Asasi and, Toby Maher from u USC on the two pivotal trials in ILD, the RECITAL trial, rituximab and cyclophosphamide. And then the other trial was the five Brineer trial with Nirandomolast from New England Journal in June. Great session, you should look at it.

But here's a report asking about how are we doing a screening, which is the subject of next week's Tuesday at Rheumatology. So they did a meta analysis of nine studies, thirteen eighty RA patients. The prevalence of RA ILD range from seven to forty three percent. When diagnosed by high res CT scans, it was nineteen percent. So while these studies did not look at risk factors, and we know there are some risk factors, especially for RA ILDs, the three S's, remember three S's, smoking, seropositivity, and sex, sex being males, males, smokers who are seropositives, much higher risk for ILD, especially UIP ILD.

They didn't look at this in a study, but they did show that being male and smoking was, twelve percent higher compared to those that, were otherwise. And then, disease onset of RA was seven years later in RAILD patients. It turns out in their study, disease activity, assessments overall didn't matter in risk of future RAILD. A prospective French study looked at telomeres and there's a buzz about short telomeres being a risk factor for, ILD. It's been seen in other forms of ILD.

This is a study in one hundred and one RA ILDs who are older, age 66, and they looked for short length telomeres. These are found in WBCs. It was seen in forty three percent of patients and was associated with lower FVCs, eighty two percent versus ninety three percent are predicted. Lower total lung capacity is forty nine percent versus sixty three percent, greater decline in both FVC and DLCO over time, meaning twelve months, and overall lung progression was worse if you had short telomeres. Not something we do or talk about, it's a buzz in the pulmonary literature.

I'll point you to a nice written by Janet Pope asking the question, what is iPath? It's a nice quick read, very clear cut as only Janet can be. Idiopathic interstitial pneumonia with autoimmune features is called IPAF. These are people who don't meet criteria for a CTD ILD. If they did, it would be called a SARD, systemic autoimmune rheumatic disease with ILD.

SARD is what we use in rheumatology. Pulmonology quite isn't using that term yet. They're still using CTD ILD. And this was, you know, a diagnosis that's based on one, having interstitial pneumonia, pneumonitis on a high res CT. Two, excluding other causes like drugs and environment, etcetera.

And three, not meeting criteria for a CTD. And lastly, having one feature, having at least one feature from two out of three domains, clinical domains, that's like arthritis, mechanics, hands, Raynaud's, or an imaging domain we talked about, or a serologic domain, and that includes ANA, CCP, Row, Row 52, etcetera. So what's important about this is that it is not in and of itself, it's a diagnosis, but it really is, a population that needs study. IPAF is to CTD ILD or SARD ILD as UCTD is to, what will ultimately become lupus or scleroderma. So it's a disease in transition.

Elena Yorns, we published a report, I think last week, about her look at IPAF patients and how they behaved over time. They behaved really poorly. They had really bad outcomes just as if they had a SARD ILD. So this is a term that we should be using and diagnosing. Last report is about polypharmacy, being very bad for RA outcomes.

This is from a early RA trial in France called the ESpA trial. This trial included four ninety seven early RA patients, and the goal was to achieve treating them with DMARDs and the goal was to achieve DAS remission. And at one year, after these people were treated with their first DMARD, if you were a polypharmacy patient, and that was people who were on two or more drugs not related to their arthritis, they achieved remission at one year, only thirty two percent. If you weren't a polypharmacy patient, you achieve remission in sixty eight percent, more than double the odds. That was almost significant.

And that was at one year. At five years, it was significant. Remission was forty five percent versus fifty six percent in the polypharmacy versus non polypharmacy groups. So again, I think it's important to note that polypharmacy lowers your odds of getting to remission at five years by forty percent, same at ten years. More importantly, being a polypharmacy patient doubled your odds of serious adverse events.

Eighty six percent versus forty nine percent. That seems really very, very high to me. Worry about polypharmacy. It's not it's not just in people who are older. It can be in any age group, but it's more prevalent in the elderly.

I wanna remind you that we have a new podcast called Derm on RheumNow. We have an August podcast, a September podcast. You may not be interested, but your your best friend, the dermatologist, should know about it. We do all the dermatology related reports on psoriasis, cutaneous lupus vasculitis, hidradenitis, etcetera. I wanna remind you this week, upcoming September, 7PM, Tuesday night rheumatology.

The subject is diagnosis screening and monitoring of ILD. We got a great panel. Doctor Shane Shapira from University of Toronto, a very wise, practical, great teacher pulmonologist. Elena Bernstein from Columbia in New York, and Brian Englund from University of Nebraska. It's gonna be a great session.

Be there. We'll talk next week.