RheumNow Podcast – To Celiac Test or Not (9.4.20) Save

It's the 09/04/2020. This is the Room Now podcast. Hi. I'm doctor Jack Cush, executive editor of roomnow.com. This week, we deliver on a promise.

Back talk has finally made it to the program. Yes. Viewer questions at the end of our news. Let's start with a meta analysis. So 11 studies that looked at, something that's been out there a while, and the question is, does hip osteoarthritis injections are they of any value?

Do they work? What if you use steroids, plat platelet rich plasma, hyaluronic acid? These have all been advocated, all been used. Turns out in this meta analysis of almost 1,400 patients shows it's not any better than placebo looking at long term outcomes and patient pain. So, again, while we often do these as temporizing measures, what do you do while you're waiting to do surgery?

It turns out this is not all that effective. Similarly is a report from a large finished database looking at the efficacy of arthroscopic partial meniscectomy. This was done in a hundred and forty six patients who had medial meniscal disease that was degenerative, and they underwent either, sham surgery or the partial meniscectomy. They looked at five year outcomes here in this fairly large cohort. It's large for an orthopedic study, and it showed that those who had the partial meniscectomy had really no significant increase in X-ray damage, but a trend towards a little bit more degenerative joint disease, almost so that if they had larger numbers, they might have actually been able to prove that menasectomy does cause DJD, is what we know.

We know full menasectomy does that. The question is whether partial meniscectomy does it. But more importantly, at five years, there was certainly no clinical benefit to having the procedure or a sham procedure. This goes along with the trend that we've seen in recent years where orthopedists are a little less inclined to do arthroscopic meniscectomies and partial meniscectomies in our patients and rather go for more conservative approaches. You know, there's some crazy data out there.

Learned this from looking at all the COVID data that you could actually look at COVID, bacterium or viral counts in sewage in large cities to figure out what the trends are going to be on COVID infection rates. It's a little scary. It's a little big brother like. It's a little disgusting, but it actually works. Similarly, there are studies showing cell phone use and location data during the pandemic shows that you can correlate cell phone activity with what happens about whether you're shopping, whether you're staying home, and it's really quite surprising, how, we can find surrogate measures of the impact of the coronavirus on society.

So speaking of coronavirus, last week, we talked about the meta analysis from Lancet Rheumatology showing that hydroxychloroquine certainly wasn't the big bad dangerous drug. It was certainly shown not to have any improvement in mortality. And when combined with azithromycin, may have been associated with more mortality. While another meta analysis was published, this time including chloroquine, hydroxychloroquine, and looking at the addition of azithromycin comes up with the same data. The antimalarials did not reduce mortality or relative risk of zero point eight three with the standard confidence intervals crossing over one showing really no effect.

Not a positive one, not a negative one, and that was in patients who are hospitalized with the coronavirus. But when you look to patients who received the combo of hydroxychloroquine and azithromycin, there was a significantly increased hazard ratio or relative risk for mortality of being one point two seven or twenty seven percent higher. Now, again, you could rush to judgment and say, hey. Hydroxychloroquine and azithromycin are dangerous. No.

It just means that they don't work. And then when you're given to the worst patients, who do you give combination therapy to? The worst patients. These are observational trials at this point. None of this data is head to head trials, one drug versus another with a six or twelve month outcome.

No. That's coming up. We're gonna get that in the next quarter. But right now, these are all the the uncontrolled observation reports all saying the same thing. Antimolarials don't work.

People got antimalarials, you're basically earmarking those who are more sick, more likely to be hospitalized, more likely to have bad outcomes. Same thing when you add on, or add in the antibiotic Zithromax or azithromycin. Bad news for an IL-six inhibitor Kevzara. You know, Sanofi has been developing this. They had one early phase two trial where it looked like only the patients received the four hundred milligram dose of Kevzara had better outcomes with regard to ventilation, death, discharge in the hospital.

So they suspended, their studies with two hundred milligrams, and they've gone ahead and they've done a phase three trial. The phase three trial did not meet its primary and secondary endpoints. Hence, Sanofi has announced that they're suspending the development of cerilumab two hundred or four hundred milligrams for use in COVID nineteen. Now this goes along with some of the data about IL-six inhibitors where some of it looked really, really good and some of it somewhat disappointing, especially in light of the fact that we've been talking about IL-six inhibitors as one of the solutions for the cytokine storm syndrome. I wanna remind you all the trials thus far with IL-six inhibitors, whether it be tocilizumab or sorrelimab, were not done in cytokine storm syndrome where it probably would work quite well.

And there will be trials that will show that data plus or negative. But these trials were basically looking at what happened when you gave any IL six inhibitor to people who are sick and in the hospital or had impending respiratory failure. And it's a mixed bag. It doesn't quite look as good as we had hoped for. It may be that IL-six inhibition should be reserved for people who have, the cytokine storm syndrome, not those who are necessarily very sick and about to go on a respirator.

So, a cohort analysis looked at patients with ANCA associated vasculitis, about two hundred fifty one specifically. They either had MPA or GPA. That's a comparative retrospective analysis of what happened when these patients with ANCA associated vasculitis and severe renal disease received either induction therapy with Cytoxan or Rituxan. And then there's another sub analysis that looked at what happens when you add it in plasma exchange or PLEX. Well, it turns out that remission rates were equally achieved by either Cytoxan or Rituxan, no big difference.

And at the addition of PLEX, now as a retrospective analysis, who's gonna get PLEX? The sickest of patients. Well, it turns out that in the sickest of patients, then PLEX did not add anything to the overall outcomes. The predictors of end stage renal disease and or renal death was really the GFR being less than 15 cc's. So again, this is good news for what we're seeing in rheumatology where we can probably move away from the use of cytotoxin and use more Rituxan, and MMF with really good outcomes in patients with GPA, MPA, ANCA associated vasculitis.

So another orthopedic journal looked at falls with total hip arthroplasty. You know, I've heard about this, we've talked about this. I've never been sure about the numbers. Well, in this study, it's a small study, a 108 patients followed prospectively. They had, osteoarthritis of the hip.

They underwent total hip arthroplasty. Their average age was 72 years old and within twelve months of having had their hip surgery, twenty three percent had an outpatient fall. Half of these fifty six percent of these falls occurred within six to twelve months, of their surgery suggesting that well I guess half of them occur in the first six months the other half occur in the second six months. Well, I don't know if that helps you but it does say that there's a fairly high rate of falls here and one maybe the only predictor for those who are gonna have falls or those who had prior joint replacement surgery prior to this. I don't know what that indicates.

Maybe the generalized ability, maybe it goes along with age. It's really hard to say but the idea is it falls are really quite common here. A question came up this week about extra intestinal manifestations of Crohn's disease and how it should be managed. So I found a very nice, review that I posted for you and some of the takeaway message in this. EIM, extraintestinal manifestations of IBD are quite common with IBD.

They're more likely to be seen with long standing disease. You don't get them right away. It's really with long it's like RA and extra articular manifestations. And you're more likely to have it with more severe disease activity, another RA parallel. And then it turns out that some of these EIMs, peripheral arthritis, enodosum, sweet syndrome, oral ulcers, and episcoritis are associated with activity.

So that's all I think helpful information. Other axial activity for instance and, pyoderma gangrenosum not necessarily associated with activity. So there are a number of drugs. The classic drugs that are eligible for use with management of these EIMs is the TNF inhibitors, the integrin, drugs like betelizumab, the JAK inhibitors, and the IL-twelve twenty three drug ustekinumab. We know that the TNF inhibitors work very well at, the arthritis and the ocular manifestations of, IBD.

They are also good at pyoderma gangrenosum and other skin manifestations of IBD. The integrin, vedalizumab drugs are somewhat effective at arthritis and arthralgia, we reviewed that in the past and also at enodosum, but have not been shown to be effective at pyoderma gangrenosum. That's vedalizumab and nadalizumab. The JAK inhibitors, as you know are now being approved for use in higher doses, if that's allowable or not with ulcerative colitis. Anyway, we know these work in psoriatic disease, psoriatic arthritis.

More recently, it looks like in the psoriasis and maybe even in spondyloarthritis with the recent use, upadacitinib data shown at EULAR showing that that works. Tofacitinib is back in studies looking at its effects on spondyloarthritis. And the JAKs, as you know, have been surprisingly effective in a lot of different skin disorders and such has been the case with skin disorder associated IBD. Lastly, ustekinumab seems to work, when all other therapies fail, especially arthritis, cutaneous, and ocular manifestations, consider those. So, seroprevalence in healthcare workers, we talked about this.

A nice report from the CDC and MMWR, a study of almost 1,300 patients, sorry, healthcare personnel showed that, in this large cohort, six percent were positive for antibodies suggesting the presence of prior SARS CoV-two infection and that twenty nine percent of patients who had SARS CoV two antibodies were asymptomatic in the months preceding that. And then most patients who were found to be seropositive had never received the diagnosis of SARS CoV two. So, you know, my hospital is not doing routine or regular screening of health care workers, and I've often wondered whether we should. I don't know about you, but we have to answer a questionnaire every day. You know, have you been exposed?

We have to have a temperature taken every day. I do think periodic monitoring of healthcare workers makes sense because you wanna keep your patients safe. So we have two questions for BackTalk. BackTalk, can find, the icon for it on our email, and also on our website. You go there, you click on the button, you have to do it your computer, you can't do it on your phone.

I can't do it on an iPhone, but you can do it on an Android phone. But generally do it on your computer and you record your question to me or to others there. It would be great if you could tell me who you are, where you're from, and what kind of rheumatology you practice because I really only want this to be questions from rheumatologists. So let's see what happens when we take a few questions. First question is going to be from Sandra.

I hope you can hear this. If not, we'll work on, putting this in but here's a question from Sandra.

How does Doctor. Cush feel about withdrawing hydroxychloroquine for senior patients?

Sandra, good question. Thank you very much. If you followed RheumNow this past week, I didn't cover it in this podcast, but on RheumNow this week, there was an article written, and actually I tweeted this about two weeks ago and this past week, MedPage today wrote an article for us, about a study in New York City of lupus patients who are older over the age of 60, who, had to stop their hydroxychloroquine. It was like, I don't know, 40 or so patients, and they showed that you could successfully withdraw hydroxychloroquine in these 40 or so patients who had to stop the therapy usually because of eye problems or retinal problems detected on screening. There are other toxicity issues and this was just in elderly people.

So Sandra, I don't know if your question had to do specifically with lupus patients taking hydroxychloroquine or even RA patients. But basically, the longer you're on hydroxychloroquine, the more you have the risk of developing eye toxicity. And if you're following patients long enough, you'll see more eye toxicity. So yes, you can safely stop hydroxychloroquine. You can stop it abruptly.

And I guess in many patients, at least in these lupus patients that were followed, they were on other background therapies. So stopping hydroxychloroquine did not make a big difference in overall lupus activity. If it's your only drug for either lupus or RA, you may have to substitute other DMARTs, consider that. Another question, this one's from Matthew.

So my question for Jack is this, when you do an extensive workup with somebody who's referred to you for a positive ANA and especially a positive ANA that's like one to three twenty or higher, where does celiac disease screening fit into the differential? I know there's some obvious facets where maybe there's a rash that looks like dermatitis, hepatiformis or GI symptoms. But where do you find celiac disease screening to be helpful? Because obviously it's not a great test with regard to positive antibodies being present. Of course it is better on the negative side.

So just kind of curious about that and seeing what your thoughts are especially if you do an extensive amount of screening elsewhere and you don't find rheumatoid arthritis or other antibodies that would be consistent with an autoimmune condition. Thank you.

Thank you, Matthew. Interesting question. So his question has to do with, you refer to patient with an ANA, solid ANA one to three twenty. When would you do testing for, celiac disease? And, you know, here we're talking about the TTG antibodies, endomycin antibodies, EMA's, and deaminated gliadin peptides or DGP antibodies.

You know, number one, I don't do further testing on people who are sent to me with an ANA that can't be explained. That usually is people hunting for a diagnosis and obviously we know in rheumatology that such consults are kind of easy because most of them never have anything or they have an ANA with a demonstrable cause like miscarriage or prior thyroid disease or prior liver disease or even age. There's a number of different reasons why someone have a positive ANA. The bottom line is one in ninety ANAs have are gonna be lupus, and after that, there's usually not much, you're gonna find and hence most ANAs that are positive aren't useful. The same can be said about testing for celiac disease.

The guidelines out there on celiac disease testing basically are don't do any testing unless you have GI symptoms. If you're gonna do that battery of celiac antibody tests for people with strange symptoms and non enteric symptoms thinking you're gonna identify some kind of systemic disease, well, that's a pipe dream. That ain't gonna happen. You know, it's sort of like it's less effective than ordering TSH and T4 when you're trying to explain someone's arthralgias and myalgias. I don't know about you, I've done that about 20,000 times in my career and found it to be useful twice.

Now I know the data on occult thyroid disease and lupus and RA and blah blah blah, but again, fishing for the cause of symptoms with a test that's not usually otherwise indicated, like you shouldn't order TFTs unless there's clear cut clinical evidence of thyroid disease. You wouldn't use that to explain musculoskeletal complaints and the same can be said about celiac disease testing. Again, it does speak to the bigger issue of when you should do testing, and again I think it's the lawyer in me that says, and I'm not a lawyer, but I've learned from lawyers, don't ask a question unless you know what you're gonna do with the answer. And that's the problem with doing tests like celiac disease testing. Hence, yes, I've done hundreds of them and I can think of one interesting case, where the GI person had to do a small bowel biopsy and whatnot and that's how you make the diagnosis of celiac disease, not with these antibodies.

These antibodies have some utility in people with proven disease but are useless in finding disease or occult disease. That's it for this week on the podcast. Go to our website to check out, these citations and more. You can click on back talk and give me some back talk and give me some questions. That would be okay for our next podcast.

Next week, we're gonna be off. We're not gonna do a podcast. It's gonna be a reprise. Next week, we're doing, a series of reports on reproductive health. Look for that.

But we'll take more of your questions in the future. Take care.