Depends On Where You’re Looking (8.9.2024) Save

It's 08/09/2024. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. We're smack dab in the middle of summer.

Hope you're enjoying yours. Hot fun in the summertime, as they say. Today on the podcast, the title is Depends on Where You're Looking. There are several of these reports that I'm going to go over where the conclusion of the research may not be right because the results were skewed by who they're looking at and how they looked at the data. I think you need to be careful about interpreting some of these articles, and know what they really mean, and I'll try to comment on that along the way.

Let's begin with a straightforward article from New Zealand, where the Rheumatology Association of New Zealand did an audit of three fifty five new seropositive patients referred, for care. And the question at hand here is, are they getting referred in a timely manner and are they being started on a DMARD or a biologic within six weeks of, the referral date? And, what they showed in the three fifty five patients, that sixty five percent met the stated New Zealand goals that they should be starting on a DMARC within six weeks. The question is what, influenced that? And the main takeaway here was it was manpower.

And they showed that if you had at least one or more rheumatologists per 100,000 population, eighty percent of people were starting on a DMARD within six weeks. If it was less than one, it was gonna be less than sixty five percent, which is what the takeaway was for the overall study. So it's manpower that determines referrals and determines how quickly they get on DMARR therapy. They also said rurality, meaning patients in rural environments were less likely to get referred and get seen, was my take on that. So this informs, our many important manpower decisions that we have worldwide.

New Zealand, Australia, Europe, South America, and North America as well. A study that caught my eye this week was a study of the association between RA and periodontal disease. As you know, that the similarities in the biology between inflammatory synovitis and the periodontal tissues, same cells, same cytokines, same, destructive potential, etcetera. And we do know that periodontal disease is a, forerunner or harbinger of RA or worse RA. And the question is, if you treated, periodontal disease, would RA get better?

I haven't seen a lot of good studies on that. And this is an exploratory smaller study of twenty two patients with moderate to severe periodontal disease. And they were seen at regular intervals by dentists, got regular treatment for periodontal disease, and everybody that got treatment got better as far as their periodontal disease. But did that influence the RA outcomes? It turns out not so for, the moderate, RA patients, or moderate periodontal disease patients, but the ones who had severe periodontal disease had a significant reduction in dash 28 scores and also in CCP levels.

I thought that was important. So I think that the take home on this is that as part of your joint exam, you should be looking inside their mouth as part of your counseling. You should recommend losing weight, stop smoking and fix your teeth. That's an important part of RA management. A retrospective study from Tokyo looked at one hundred and ninety four Behcet's patients.

How many Behcet's patients do you have? And I like these numbers because you don't see these kind of numbers, but in their review of their Behcet's cohort, they found that twenty five percent of patients had evidence of intestinal Behcet's, which obviously is, more aggressive, maybe harder to manage, and Behcet's itself is hard to manage. What they, showed in this study was that, and this is sort of this head scratcher here, is that the if the Behcet's patients were on PPIs, that, it significantly increased the odds of having intestinal Behcet's. Now what's the connection between gastric acidity and intestinal Behcet's? I don't know.

I mean, there's ulcers here that are involved with gastric ulcers and duodenal ulcers and the need for PPIs, which is not the same as the ulcerations that are seen in the mouth and gastric mucosa or GI mucosa in Behcet's, but maybe there is. I think this is one of those issues about where you're looking. Behcet's patients who are on PPIs, you're looking at their GI tract, their GI symptomatology, and hence, you're more likely to diagnose intestinal Behcet's. I must say that in my many Behcet's over the years, a real minority, and I gotta say ten percent or less, probably five percent or less, actually had proven Behcet's with, colonic usually it's colonic ulcerations that I found, and rarely gastric ulcerations. But nonetheless, I think this is a quizzical issue and one that's open to interpretation that can be solved by a better study, and actually endoscopic, evaluations of these patients who really know the true incidents.

Another sort of head scratcher comes from California, and a cohort study of nineteen thousand three hundred and forty rheumatic disease patients. And they basically showed that those patients who had cardiovascular events in their history, one point four percent of that nineteen thousand, or anti phospholipid syndrome in five point five percent, these people had a greater risk of adverse pregnancy outcomes, obviously had to be a woman and had to be pregnant, and have either cardiovascular events or antiphospholipid. No problem with cardiovascular events. We certainly know they're linked to adverse pregnancy outcomes. That's really important.

But cardiovascular events, influencing pregnancy outcomes, I don't know about that. I think really what this is saying is that if you've got a rheumatic disease with cardiovascular events, you're more likely to have more severe disease. And more severe disease, we do know, is associated with worse, adverse pregnancy outcomes, APOs, if you're a pregnancy maven. A large prospective vasculitis study in patients with Takayasus, another large number, two thirty six patients, found ninety two percent of the women that they were 36 years of age on average and had a disease duration of less than three years. The important point of this study was that they found evidence of vascular damage at baseline in eighty percent or more of patients.

But what they were really doing was that they were looking at a tool called the VDI, the vascular damage index, which is a listing of like 64 items, each of which has some relationship to vascular damage, but in and of itself is not evidence of vascular damage. And so I don't know what that really means using this tool because you don't use the vascular damage index in your assessment of patients. And I and but I do think that what was important was that even at the onset, these patients may have vascular damage, but more importantly, they will, a high percentage, thirty, forty percent will develop vascular damage, in the next few years. The question is, and the reason maybe why I bring this up, is how do you assess vascular damage in Takayasus? I know the way I do it.

I try to get imaging at baseline. I try to get, MRAs, and or actually angiograms of the arch and whatnot. I do detailed pulse examinations, but you could use a tool like this to assess damage. And then how do you assess the difference of vascular damage, which may not be modifiable, versus vascular inflammation, which, you know, your pulse assessments can change. The angiographic, stuff may change as well.

So I think this is a real big challenge, and I really am looking to the vasculitis mavens to come up with better tools that are actually more useful for those of us in practice in managing patients with MPA, GPA, EGPA, large vessel vasculitis like Tachyasis and GCA. I think that's really important. And you know, it's an important thing right now in in patients with GCA and with PMR to be thinking about doing vascular imaging. Certainly, newly diagnosed GCA needs extended vascular imaging at the outset. That's part of the new guidelines.

An EU study, it's a U STAR study and another European cohort study combined their data for fifty two patients with systemic sclerosis to look at how often they get, early immunosuppressive use. That would be methotrexate, mycophenolate, etcetera. And what they showed was that the patients who did get early treatment, which they defined as the first three years of scleroderma, I think that maybe is a little too late, but nonetheless, about half of them met this criteria. It was fifty two percent and those that did get earlier treatment were more likely to be male, have diffuse disease, and that the most common drug used was methotrexate in sixty percent of that five hundred forty seven patients. Only one point seven percent at that point had received a biologic.

What they did show was that, ILD was found in these patients in half the patients after three years. And so I think that the idea is that maybe we need to like we're worried about RA and manpower leading to RA referrals and earlier institution. I think the same goes true for systemic sclerosis where we do need earlier interventions. A quick, note about MAS, a systematic review that I'll list for you, 57 reports, eleven forty eight MAS patients, almost nine hundred of those from JIA, one hundred and thirty seven from lupus, showed that the most effective therapies by the analysis was high dose glucocorticoids, IL-one inhibitors effective in eighty three percent of patients, and gamma terferon inhibitors, that's emapalumab, there's only one that's on the market, emapalumab, effective in ninety three percent. And these were especially so when these studies were largely done in systemic JIA patients.

They do say there's good evidence, that supports the use for the calcineurin inhibitors, cyclosporine, etoposide, and even JAK inhibitors, and they specifically mentioned ruxolitinib. You may have seen, the gout forecast data from Lancet Rheumatology that by this is a sidebar to the global burden of disease study that came out in 2021, that they are estimating that by 2050, let's see, this is 2024, next twenty five years, there's going to be a seventy percent increase in the number of gout patients. So there's ten point three million in The United States with gout. As of 2020, there's fifty six million people globally who have gout. The prevalence of that is six fifty nine per one hundred thousand, and that was already a twenty two percent increase over the 1990 numbers.

So they're suggesting this, fifty five, fifty six million is going to go up to ninety six million alright, by 2050, and they say that the main reason for that is population growth. That's the main reason. Obesity is an important contributor, we have an obesity epidemic and also as is chronic kidney disease. Three more reports, the UK Biobank, did an eleven year study of gout and they said things that you know, but I think a few things worth, repeating. We do know that beer and cider champagne, increased beer, cider, who drinks cider, champagne, and, do increase the gout risk almost at any goat, certainly beer.

But they did show in this study of five thousand seven hundred people that in women, light alcohol use was actually associated with a lower risk, a twenty two percent lower risk. And you know alcohol is anti inflammatory, even though it may impair renal handling of uric acid. Maybe in women, it doesn't drive the risk so much, if they stay away from beer. And then also that light red wine, use also reduced gout risk, not to the same degree. So maybe that affects some of your counseling, maybe it doesn't.

Two studies about spondylitis, a study of one hundred and thirty six patients referred, with low back pain found that the cause was degenerative disc disease in seventy one, DSH, diffuse idiopathic skeletal hyperstosis in thirty eight, and, looks like twenty percent, twenty seven patients had axial spondyloarthritis. The important part of this review of consecutive patients referred with low back pain is that the features that you find with one may be seen in the other two. So they kind of in a very confusing way did show that, when they looked at things like SPA like evidence or evidence of SPA on imaging, degenerative disc disease on imaging, bone marrow edema, fatty lesions, that basically the spa like image features on radiography found in one quarter of the patients would dish. Then by MRI, bone marrow edema, all the patients, a third of the patients had evidence of bone marrow edema, suggesting a lot of things that we hang our hat on in the diagnosis of low back pain may not be so specific. For instance, we do know the most specific MRI finding in spondylitis is going to be SI erosions more so than bone marrow edema.

We talked about that in the past. The other, article I really liked I'm going to end with comes from Walter Maximovich and, his colleagues. They did a very large study where they, two different cohorts, where they were studying three sixty three patients, and these patients were patients that were being seen in dermatology clinic for psoriasis, in ophthalmology clinic for uveitis, and in GI clinic for inflammatory bowel disease. And if any one of those clinics had patients with low back pain, they were automatically referred to the rheumatologist. Rheumatologist did his thing, with a clinical assessment, Sedrate, CRP, B27, conventional radiography, and if warranted, MRI.

So not everybody in the first cohort got MRI, I think was about half, but everybody in the second, cohort got MRIs. And the surprising thing was that even though these patients were being seen and largely primarily followed in the derm, ophthalmology, and GI clinics, that sacroiliitis was found, on X-ray in thirty four, to sixty percent of patients. Ankylosing spondylitis I'm sorry, axial spondyloarthritis, the definition by EULAR criteria, forty seven to sixty two percent in one cohort, twenty three to fifty eight percent in another cohort. And and the finding of spondylitis was highest in the uveitis group. Right?

I think we you you might have guessed that already. But, and often a lot higher than in the, in the IBD or where it's about twenty percent maybe or in the, psoriasis group where it's probably less than twenty percent. Bottom line is that if they also had b twenty seven, it significantly increased the odds of axial spondyloarthritis ranging from, I think, about sixty to eighty nine percent. And they did, not surprising, because Walter's an imaging guy and he's the expert on the, use of MRI. The one of the takeaways was that MRI did increase the odds of a diagnosis of spondylitis.

The point of the study is for psoriasis, uveitis, and acute anterior uveitis and inflammatory bowel disease, the presence of low back pain should warrant referral and a deeper investigation for the possibility of spondylitis. Anyway, that's it for this week on the podcast. You can go to the website to check out these citations and more. Remember, hot fun in the summertime. We'll see you next week.