NHANES, Numbers, & Risk (7.18.2025) Save

It's 07/18/2025, and this is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week on the podcast, we're gonna do a few questions from you, audience, and ask Cush anything. We're going to cover some autoimmune things, a bunch of studies like from the NHANES about rheumatoid arthritis, some Still's disease, and we'll end up with ILD.

I want to start out with an announcement of something you may have already noticed. Last week was our first week of something called Room IQ. Room IQ is a quiz tool that we've been working on for almost three years. And it's pretty involved, but the idea is to come up with an interesting, for you. And we'll be using it in a lot of different ways, but the basic way that we're going to use this is at the end of this week when you are hearing this podcast, probably a day or two after, you'll get an invitation to take the Room IQ weekly quiz.

I want to say that almost 800 of you took it in the first week, which was impressive. There was a Bell distribution. It's a pretty simple, easy quiz to take. It's almost modeled a little bit after Who Wants to Be a Millionaire. It's a multiple choice and sometimes true false question format.

It'll take you all of a minute or two. And you'll learn something from it and hopefully you'll like it. Give it a try. My suggestion is sign into or log into the RheumNow website and take that because then your name will be up there on the leaderboard and everyone will know how smart you are and this does get competitive at some point, does it not? Let's get back to the podcast.

Lupus is always a challenge in one way or another, but lupus and stroke is sort of an interesting topic. It brings to mind the issue of either neuropsychiatric lupus, used to call it lupus cerebritis, or antiphospholipid syndrome. In this one cohort study of forty lupus patients, versus one hundred and twenty controls, they looked at people who had stroke. So it's forty lupus with stroke versus one hundred and twenty controls who don't have lupus who had a stroke. And overall, having lupus in this mix is associated with poor outcomes, especially with regard to recovery, recurrence and mortality.

So, when you looked at the numbers and the outcomes, I think these people were followed for, on average, eight years, I want say, that the stroke mortality was higher in the lupus patients, although it did not achieve significance. But overall, all cause mortality was thirty seven percent in lupus, eight percent in controls. Recurrence of stroke, obviously higher in lupus, threefold higher, thirty percent versus nine percent. And the incidence of post stroke seizure was seven times higher, twenty three percent versus three percent. So stroke and lupus can be a bad thing.

Pregnancy is always a challenge in our patients. A cohort study from the Swedish birth registry looked at patients who had a diagnosis of systemic sclerosis, looked at their pregnancy history pre and post diagnosis. Prior to the diagnosis, were there ninety four pregnancies, I guess nine seventy eight afterwards. Bottom line is that post, diagnosis there was an increased risk in scleroderma patients for preeclampsia, 3.8 fold higher, preterm birth also three fold higher, and cesarean sections, 2.5 fold higher. What was not changed was maternal risk, maternal outcomes, neonatal death, and there was no differences in stillbirth.

Sjogren's Syndrome, another autoimmune disease, had an interesting report this week about the utility of serologic testing. You often will do SSA, SSB, Roe and LAW testing to establish the diagnosis, but it may actually have a greater import than diagnosis. It turns out that those who had SSB more so than SSA, and both were significant, tended to have an abnormal DLCO. That's fairly predictive, with an AUC of 0.8. Turns out that most of these people, were more likely to have lymphocytic interstitial pneumonitis.

And again, lung findings, low DLCO, lymphocytic interstitial pneumonitis was even more likely if you were quadruple positive. SSA, SSB, rheumatoid factor, and ANA positive. I got to say, I don't see much in the way of Sjogren's syndrome lung disease. But if I did see quadruple positive, would I worry more? Frankly, my answer would be no.

But I can't argue with you know, cohort based research, so now I'm more likely to take a look at this. Speaking of lung disease, one of the ones we do worry about in our patients with rheumatic disorders, autoimmune disorders, and immunosuppressive use is Pneumocystis, Uroveci, PJP pneumonia. Interesting studies showing that sulfasalazine is protective against Pneumocystis in RA patients. Now, my RA patients don't have much of a risk for PJP. Hence, even if they go on Rituximab, which is a risk factor for PJP infection, I'm not going to be putting them on prophylaxis.

I'm not. Not in The United States, not in Dallas, Texas. But where this study was done, which I believe was in Southeast Asia, five ninety four RA patients with eight hundred plus treatment episodes, almost two hundred on sulfasalazine, six hundred not on sulfasalazine with eight fifty patient years of follow-up. There were a total of twenty one episodes. This is a high risk population based on area or population.

Twenty one out of almost six hundred patients had PCP, PJP, three died. And it turns out if you were onesix of the population that was treated with sulfasalazine, there was a significantly lower risk, P. Three, rate ratio zero point five. I find that surprising but also encouraging. There is an antibiotic component, is there not, to sulfasalazine?

Maybe that's why you're seeing this. Two reports about NHANES. NHANES looked at over 38,000 patients, trying to see if there may be risk factors for developing RA based on commonly available labs like neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, monocyte to lymphocyte ratio, other things called systemic index or Siri. They looked at NPAR as well. NPAR is the neutrophil to albumin ratio.

Never seen this one before, but the results are interesting. Thirty eight thousand people at NHANES who have followed with questionnaires, for about a twenty year period, they found that an elevated NPAR, neutrophil to albumin ratio, was a significant risk factor for the development of RA. Comparing the top turtile to the bottom turtile, a twenty seven percent increased risk, especially if the NPAR value is over 13.6. It seems like a lot of letters and acronyms for what seems like a significant but small benefit. But this is the kind of data that you can apply to populations, that AI can apply to your population and tell you who might be at risk to develop rheumatoid arthritis.

Now this was done in all people in NHANES, nurses, women, but what if this same analysis were done in people who would clinically suspect arthralgia? Maybe they'd have the same things. I like that kind of data. I like that kind of thinking. And Haines also studied the risk of kidney stones in RA.

I'm adverse to this right from the start. I always teach there's a negative relationship between RA and gout. If you've got RA, you're not likely to get gout. If you've got gout, you're not likely to get RA. But you and I know because we're experts, right?

Are we not? We see tons of both. There are a few people that do have RA and gout. Estimated to be less than eight percent depending on where you're looking at RA populations, and probably less than that if you're looking at a gout population. I don't know.

It's kind of screwy. I like the teaching point you can't have both because I'm usually teaching primary care internists, people who don't see the volume we see, and they're just screwed up by the clinical presentation. Do a rheumatoid factor, do a uric acid, that'll help you figure it out. But here, NHANES, again nineteen thousand people followed for twenty years, almost fifteen hundred who had RA, the prevalence of kidney stones, which I often relate to uric acid and nephrolithiasis, was higher in RA. Seventeen percent of RA patients had nephrolithiasis versus eight percent in the population, a seventy seven percent increased risk, that was significant.

So, you know, that RA patient with flank pain, I'd still want to think, is it really RA? Could they have gout? But this says it can happen. Interesting. Another RA study I published this week, I published it because it says something I was saying fifteen years ago, twenty years ago, and that is an RA patient who goes in rapid remission on anything.

On, you know, sulfasalazine, methotrexate, a JAK inhibitor while playing Tetris, it don't matter. If they rapidly go into remission, they're going to have better outcomes. So rapid responses, I was trying to convince a company long, long ago, company and drug will remain unset. I did an impassioned plea. Rapid changes in -twenty eight CRP within six weeks would predict ACR 70 and better responses.

They never did the analyses. There have been a few reports that have sort of suggested that point. In this study, eight sixty five RA patients who were being treated. And the outcome measure they were looking for was a DAS ERP of less than 2.6 in less than twelve weeks, not necessarily rapid, but we'll just call it an early, maybe fast response, that occurred in twenty eight percent of this cohort of nearly nine hundred patients. And it turns out that those who met that criterion at week 12 were more likely to have better responses at week 26.

Rapid remission, again, dash 28 less than 2.6 by week 12 was associated with significant downstream five year benefits with better outcomes with regard to swollen joint count, tender joint count, fatigue, HAC pain, function, most patient reported outcome, PRO, measures. So I'm reporting it because I was right. And I like finding data that proves the story that's in my head. Report, by the way, stories that disprove the stories that I have running around inside of me, but this one was a win and let's be happy today. A study of two studies on Still's disease, one a biomarker and one, coming from a select population.

This is from the island of Martinique. It's in The Caribbean where they have largely an Afro Caribbean population. It's a mix of many cultures with a lot of African culture in there. This is a study of three fifty thousand individuals between 2000 and '4 and 'twenty two. They diagnosed and in this report, talk about, thirty three cases of Still's disease.

Seventy one percent female, it's usually half half, eighty percent with systemic disease, twenty percent with articular disease. You know, when it settles down into articular disease, that's no longer acute Still's. That's kind of like what happens in the twenty percent who continue to have arthritis after the systemic disease is dying out. But anyway, in their collective experience, it's eighty percent and twenty percent. Ninety one percent met Yamaguchi criteria.

Interestingly, the thing that really differed in this population was they did have more women. They did have maybe a few more older than 35. Half the population was age 35. I think it should be about eighty plus percent are 35. And we're seeing that in a lot of STILS reports in the last few years.

There's been a skew towards it being described in older people, which I don't necessarily buy as being valid. But if they meet Yamaguchi criteria, nine percent didn't here, and they're 53 years old with the onset, I guess I could go along with that. The other big finding here was they had a very high percentage with, pulmonary disease, and that's, was fifty one percent. Pulmonary disease as manifest as pneumonitis is going to be in less than twenty percent of adults with Still's disease, right? Pleuritis is going to be like thirty, forty percent.

But pulmonary disease, fifty one percent in this Afro Caribbean population, and those people were largely ninety five percent systemic pattern onset. The overall prevalence was seven per one hundred thousand. And again, those so a lot of this is really in agreement with the worldwide descriptions of Still's disease except for this, why do they have more women, why do they have more older people, and why do they have more lung disease? Again, we adults don't see a lot of lung disease other than pleuritis. The pediatricians that are seeing systemic JIAs, also called Still's disease, will teach us that this is a big problem, that it can be seen in up to twenty percent.

They worry that it could be a DRESS syndrome, a drug reaction, maybe to our IL-one or IL-six inhibitors. But the lung disease manifests in multiple ways. It's, you know, alveolar proteinosis, it's ILD, it's a whole bunch of different diets. Doesn't have one unified pathology or one clear cut risk factor or whatever, but they're seeing it and they're worried about it because the outcomes are not good. Pay attention to the lung disease.

When I did my first report on Still's disease, 21 patients from the University of Pittsburgh in 1984, my good buddy, Orrin Traum, was on the same podium talking about his 20 plus patients from UCLA, I believe is where, or LA County Hospital describing lung disease. So it's been out there a long time. Another study coming from a Chinese cohort looked at a new biomarker UBE2D1. Maybe you won't be able to fall asleep at night because I got that in your head. But this was identified by doing basically RNA seq and bulk RNA seq analyses in a good sized cohort, they found that this, marker that's a protein, that's found, the product of monocytes, it activates monocytes, it reflects enhanced monocyte activity, monocytes being the garbage pails that have tons of pro inflammatory cytokines and inflammatory mediators.

I'm not surprised it's elevated. But what they did find that this was not only correlated with systemic disease activity but was superior to other biomarkers including ones that you use, the S100 proteins like calprotectin, IL-eighteen which we might be using more in the future, and ferritin which you all do. I wonder if this UBE2D1 may be a marker for, MAS like ferritin and IL-eighteen can be when those are very, very high. But they actually suggested in the paper that that was not the case. So like finding biomarkers on a disease, that's hard to understand.

But anyway, let's move on. MDA-five dermatomyositis, interesting cohort, not restricted, geographically found worldwide. This study of 176 patients who were MDA-five positive versus fifty five controls looked at, with other diseases found that the presence of, type interferon or alpha interferon antibodies was seen in eighteen percent of MDA-five patients, and those who had it were more likely to be older, greater than 60. They were also more likely to have one of the worst manifestations of this particular cohort, and that is rapidly progressive ILD. It's found in the for those positive in sixty eight percent who are positive versus forty one percent in those negatives, so a fifty percent increase at least.

And they also had more pulmonary infections, seventy one percent versus forty six percent, and a high number of opportunistic and fungal infections that were significant. So I like this kind of research. I think we should be, I would like to have access to testing for how active is Type one Interferon and what's going on in my patients. I think it could help inform A, the treatments we might use and B, maybe the things we should worry about. Two more reports, one from the CDC and MMWR.

One in five patients with arthritis don't know their diagnosis. What? Again, NHANES study from 2020 that found that the overall prevalence of any kind of arthritis as reported by the patients in adults was sixty seven million. That's the highest number I've seen so far or twenty seven point nine percent of the population. Chronic arthritis is still around fifty two, fifty three million.

Who are these sixty seven million, that they're identifying in this survey? Thirty three million with osteoarthritis. You know, that's kind of on par with what's been reported before. Twenty seven million comes to mind. Psoriatic arthritis, about a million.

That's kind of on par. Rheumatoid arthritis, ten million. Ten point six. Uh-uh, sorry. Consistently for the last twenty years the number of people, prevalence of rheumatoid arthritis in The US is one point three, one point six, you know, not ten million.

So there's an inaccuracy here, is it not? So these are patients reporting on their diagnosed arthritis. But the interesting thing is that twenty one point six percent or one in five did not know their type of arthritis that they had. That amounts to fourteen plus million don't have a diagnosis. Not likely to know the kind of arthritis you have is higher still, a little bit higher, you know, five-ten percent higher if you're black, Hispanic, Mexican American, of low income, less education, and with no health insurance, where the percentages go up from twenty one percent to twenty seven-thirty six percent.

Again, this is disquieting. There's knowledge gaps here that only you and I can fix. But patients have to have the initiative to find out their diagnosis and we need to be clear. There's a lot of people being told they got rheumatoid when they ain't got rheumatoid according to data. What you need to know is that National Health Interview Survey projects that arthritis will increase by two thousand and forty to seventy eight million Americans.

My last report is on interstitial lung disease and the risk of cancer. I am featuring it here because I want to let you know that in the month of September, we're going to be doing a a month long campaign on interstitial lung and autoimmune lung disease. I think you're going to like it. We're working on it now. There's a lot of action in this area.

This JAMA report comes from the Swedish registry of 5,000,000 Swedes, amongst whom there were fourteen thousand six hundred plus with ILD. When you look at the risk of lung cancer, it's like twenty six per one hundred thousand if you don't have ILD in Sweden, but three fifty five per one hundred thousand if you do have ILD. After a lot of, you know, adjustments and analytics that the overall hazard ratio risk is a twofold increased risk. The point here is, you know, I don't want my patients to get ILD. I should be looking for it, and when it's there, not only should I consider what I can do to be aggressive or how I'm going to follow it, I think the findings should also prompt you to consider a risk of lung cancer.

And it turns out there's all kinds of lung cancer. We'll end with two, Ask Cush Anything reports. I'm going to just read them. Doctor. Magdi Iskander from Ohio, sent in a recording asking, What do I do about stopping and restarting upadacitinib in a patient who is of going to Peru and needs to receive a yellow fever vaccination, a live virus vaccine.

So this came up with the CDC and their advisory committee and vaccine advisory committee long ago when we had a live virus, zoster vaccine, and how would you do that? And I think the rules first apply in that the patient should be if there's a risk of reactivation based on the patients being immunosuppressed or the drugs that you're using, then you should be off the drug before you get the vaccine for up to thirty days, get the vaccine, and then restart the drug two weeks later to allow the vaccine to work. Again, the idea here is that anticipated immunosuppression raises the risk of dissemination of a live virus as opposed to the protection afforded by the vaccine. But now you've got to think of a few things. So I always teach people that if someone's going to get a yellow fever vaccine and they're going to a place where yellow fever still exists, where are they going?

Are they going to be staying at the Taj Mahal Hilton? Or are they going to be working in Calcutta with poor people where there's a much higher risk of getting it? They got to be a traditional tourist. They don't really need the yellow fever vaccine and you can write a letter that says, My patient's immunosuppressed. Taking immunosuppressives that are life saving to receive this vaccine poses much more risk.

This patient can travel without the vaccine. And that will suffice so that they can get their visa to go. Secondly is what are the rules here on a patient on a JAK inhibitor? JAK inhibitors are fast on, fast off drugs, much more so in TNFs and rituximab and things like that. And can this patient go off of a JAK inhibitor for three to four weeks.

Know, JAK inhibitors start to have their effect in two weeks. The people go off JAK inhibitors start to get worse at two weeks. So can your patient be off of a JAK inhibitor? I would use the rule I use for methotrexate. Meaning, I want to stop methotrexate for a week, give the vaccine and then a week later give the methotrexate and no one will flare with methotrexate.

With a JAK inhibitor, I'd want them to be off a JAK for a week. I'd give them a vaccine and I'd start a week later or two weeks later. But this is a live virus. Again, the question is what's the real risk of live virus infection and where they're going? If you don't know what else to do based on what I've said, ask an expert, ask a vaccination expert, ask an infectious disease colleague.

Another question and recording from, and thank you to Doctor. Iskander and also Doctor. Sumayya Shah from Pakistan. She asked a question about a patient with CKD who was unable to take a bisphosphonate was on denosumab, received I think up to ten years of therapy with improvement in the numbers. I would assume that means the DEXA scans.

But the question is what do you do after? What can you use? She says we can't give bisphosphonates. Bisphosphonates are cleared by the kidney. There are rules about using bisphosphonates in people with CKD.

If this patient can't get a bisphosphonate, can't give a bisphosphonate. But there is so a few things. Well, the first thing is I'm not an osteoporosis expert. When I have questions like this, I go to my partner, Katherine Dow, or I call Stan Cullen, or I call any of the great osteoporosis experts in our field, including Nancy Lane up in Sacramento. But, I do know enough to manage these situations.

I do know that denosumab has a really long half life and even after you stop it because you need to do a drug holiday, there's not much benefit to denote to a bisphosphonate after three years of use. And then, you know, three to six years, you should stop and do a drug holiday. But it's got a long half life, it sticks around. That's not the case with denosumab. You stop it, it's quickly out of the system, and then they have this rebound in bone loss and a higher incidence of fractures.

So you're right in saying these people need something else. So what are your options? One, refer to a CKD specialist. Two, refer to an osteoporosis expert. Consider the use of anabolic therapy post denosumab.

That would mean using a parathyroid hormone analog or Romacizumab. So again, I really worry about the rebound effects here.