Transcription:
The Axial Spondyloarthritis Continuum


Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine Podcast for physicians. I'm Melanie Cole. Joining me today is Dr. Eric Ruderman. He's the Associate Chief and Professor of Medicine in the Division of Rheumatology at Northwestern Medicine, and he's here to speak with us about what's new in spondyloarthritis. Dr. Ruderman, it's a pleasure to have you join us again. So, tell us a little bit about the prevalence of spondyloarthritis, the scope of what we're discussing here today.

Dr Eric Ruderman: Yeah. So, it's actually a very common problem, even though people don't think about it or realize it. When we talk about arthritis, the two things that come to mind for most people are osteoarthritis and rheumatoid arthritis. This sort of spondyloarthritis actually is more people ultimately than have rheumatoid arthritis. Probably somewhere between 1% and 2% of the population has some variant of this, and a lot of it goes unrecognized. And I think as we learn more and more about the disease, we're becoming aware of the people who have it that we just haven't thought of before.

Melanie Cole (Host): Well then, if it is a little bit different than osteo and rheumatoid, tell us a little bit about the clinical manifestations, the most common presenting symptoms and why it's sometimes underdiagnosed or there's not as much awareness of it.

Dr Eric Ruderman: So, the formal name for this is axial spondyloarthritis, which is kind of funny because axial refers to the spine and spondylo-, the root of the term is spine also. So, it's basically spine spine arthritis, which tells you what the primary manifestations are. These are people with largely back and neck problems. Now, they can get peripheral arthritis, they can get pain in other joints and in hands and wrists and shoulders and knees. But the big issue is really back. And I think part of the reason a lot of this goes unrecognized, is that there are lots of ways and reasons you can have back pain. And so, with people and docs and other healthcare providers who aren't really familiar as well as they should be with this disease, they tend to attribute back pain to all sorts of other stuff and not think about this.

Now, the key components of the axial spondyloarthritis that's different than other back pain are two things. Number one, it tends to start early. So lots of people as they get older, as they get into their 50s and 60s, get some disc disease, some wear and tear, and they get back pain, or people pull a muscle or, you know, pick something up or whatever. This tends to present in people who are under 45 because it is a genetic problem, it is a disease. It's not something that comes on that you don't get or exposed to or you have an injury. And so, it tends to sort of transpire earlier in life. And so, we look for pain that really starts early before the age of 45, sometimes as early as in their teens. It's a pretty persistent pain, so it's different than somebody who hurts their back lifting something and they hurt for a couple weeks and it eventually gets better. This is an ongoing pain, lasts more than several months. And most importantly perhaps, it's an inflammatory kind of pain. And what I mean by that is it's not just sort of muscular pain that hurts as you move or as you lean over or whatever it. The inflammatory pain says that the problem is inflammation in and around the spine. In many cases, it's sort of in the tendons around the spine and that inflammation actually hurts more at rest than when you're moving. And when you move, you actually loosen things up and people feel better. So, the common symptom that people talk about is that they wake up with a lot of pain in the morning, and then after an hour or two as they stretch and loosen up, the pain gets better. And that's very different from somebody who has a muscle problem or a disc or some other mechanical back pain because that tends to be better when you rest it and hurt more when you move around.

Melanie Cole (Host): That's so interesting. Now, tell us a little bit then about diagnosis, because as you're talking about these presenting symptoms and what providers should be aware of and alerted to as far as age and the way that it feels in the patients, then how is it diagnosed? How do we know definitively that's what it is?

Dr Eric Ruderman: Sure. So for the most part, like much of what we do in rheumatology and honestly in a lot of medicine, it's largely a clinical diagnosis that you use lab testing and x-rays and other imaging as supportive, but that's not how you make the diagnosis. And so for this, the first thing you have to do is have some degree of suspicion. Be aware that this is an issue and think about it. And the triggers for that would typically be somebody who comes to you with more than three months of back pain, persistent back pain at a young age, less than 45. That's kind of the classification criteria that we use for this. And then, you take the next step and say, "Okay. What's the nature of that pain? And is it more like the inflammatory pain that I just talked about? Are you stiff when you get up in the morning and then that loosens up as the day goes on?" That's very consistent. And so, those are first parts. That's sort of the stem of making the diagnosis. You have to start there.

And then, you look for other supporting things. And the clinical supporting things might be, "Do you have arthritis in other joints?" Because sometimes they go together. "Do you have a history of psoriasis or inflammatory bowel disease like Crohn's?" Because genetically, those are all sort of linked. "Do you have a history of what's called uveitis or inflammation of the front part of your eye?" That also is connected? I mean, they're not necessarily part of the diagnosis of axial spondyloarthritis, but they go with it and make you think that that might be what's going on.

And then, you move into the testing story. And from a lab test perspective, there are not very many things that help. There's a tissue type that is called HLA-B27. It's basically the nature of somebody. It's a genetic sort of tissue type, like who you are, okay? And that can be helpful because people who have this disease or this diagnosis are more likely to have that kind of-- that's who they are, because it's a genetically-based disease. But the problem is that's not enough. And it turns out that in the general population, maybe 8% of people, that's their tissue type and they don't all have this disease, so it's just a piece of the puzzle, but it's not useful to say, yes, you have it or, no, you don't. Because in fact, some people who have it don't have that HLA-B27 tissue type. So, it's just supportive.

The only other lab test that really are helpful are a couple of markers of inflammation, and one is called the C-reactive protein. The other is the sedimentation rate and they're very non-specific. They don't point to a specific diagnosis, but they're very helpful markers of systemic, generalized inflammation that you sometimes see with this. And that's where it also gets complicated because perhaps only 30%, 40% of people will have elevations in one of those because they just don't always have that. But when it's there, it's helpful and it's supportive.

And then, you look at imaging and part of the challenge with the axial spinal arthritis is that, historically, the way we made the diagnosis when we looked at imaging was just an x-ray, because this goes back a long time, back to the early '80s when we didn't have advanced imaging like CT or MRI or what have you. And on an x-ray, what you look for is arthritis at the sacroiliac joints, which is where the spine and the pelvis come together. And that's really the key joint in this disease. And you start to see loss of cartilage in that joint. You can see erosions or damage to the joint. And eventually, when it goes on for a long time, the joint actually fuses because it's so damaged and sort of grows across it. So, that's what you look for. The problem has always been that, while that's helpful when you see it, it's not a terribly sensitive finding because not everybody has that. And so, you have to be sure what you're looking for. And if you don't see it, it doesn't absolutely rule that out. And in the last 15 years or so, there's been a re-looking at how we classify this disease to bring in newer imaging studies like CT scans or like an MRI that are much more sensitive and can pick up changes that you won't see on an x-ray. And so to make the diagnosis, you sort of put all of that together. There's not one single thing that is a yes or no. But when you put all that together, then you come up with, "This is what it looks like, and then we're going to head down the road of treatment."

Melanie Cole (Host): Dr. Ruderman, I'd like you to speak a little bit about the difference between non-radiographic axial spondyloarthritis and radiographic axial spondyloarthritis and some of the factors that would influence the development and progression of this disease.

Dr Eric Ruderman: That's interesting. That's a bit about what I just talked about when we think about the newer. Imaging techniques that we have for this. So historically, all we had was radiographic axial spondyloarthritis, which used to be called and sometimes still is ankylosing spondylitis. That was the diagnosis, but it was almost entirely based on having x-ray changes in the sacroiliac joints where the disease was. And about 15 years ago, as we got newer techniques for imaging, people said, "Well, maybe we're missing people. And let's revisit how we classify this and diagnose it." And they basically said, "Yes, there are now people who have some changes on an MRI, but their x-ray looks normal. But they still have the same story. They still have the same symptoms. So, they really are a part of this. But we wouldn't have made that call before." It's interesting because initially the thinking was, well, that was just early, that we were just catching people before they developed the x-ray changes.

What's become very clear is that there are some people who will never have changes on an x-ray, and yet you can see it on an MRI. That's non-radiographic axial spondyloarthritis because the radiographs, the x-rays, don't show the changes as opposed to somebody who has radiographic axial spondyloarthritis, where you have those changes and we would've called it ankylosing spondylitis in the past. And it turns out that if you sort of look at the whole universe of people who have axial spondyloarthritis who have this condition, it's about 50/50 in terms of who has x-ray changes and who doesn't. And that's fascinating because 20 years ago, half of those people, we never would've diagnosed without those x-ray changes.

The other interesting thing here that is always important and I think does get in the way a little bit in diagnosis, is that women, for some reason, and we don't really understand why, women get the disease, but are much less likely to have those radiographic changes. And so in fact, in the past, we used to think of ankylosing spondylitis, this sort of classic disease as 80% to 90% men. And what was happening was, yes, the people who had x-ray changes were men because that's who gets the x-ray changes. But we were missing a lot of people who had this but didn't have those x-ray changes. And now, when you look at the whole broad universe of this, it's more 50/50, the women get this just as much as men, but they don't get the x-ray changes so people don't think about it, one, because they don't see the x-ray changes, but two, they're not inclined to think about it because we always assume that this was not something that women got when, in fact, they did.

Melanie Cole (Host): That's so interesting, Dr. Ruderman. You're such a great guest. You always have such great information. Now, speak a little bit about the treatments and the current treatments, and you can summarize the guidelines that have recently been updated by the American College of Rheumatology.

Dr Eric Ruderman: So, the treatments and the guidelines, they go hand in hand. And there are guidelines from the American College of Rheumatology. There's also some recent guidelines from the European League Against Rheumatism, that's the European equivalent of that. And they all sort of say the same thing. And it's really sort of interesting because it's different than we look at some of our other diseases. So if I can turn for just a brief second to something like rheumatoid arthritis, the treatment of that has changed dramatically over the last 20 years with all of the biologic therapies and all the new drugs that we've got, and concurrent with that has been a big effort in rheumatoid arthritis to say you need to start treating people as soon as you make the diagnosis because the damage that results from the disease starts right away, and the earlier you treat them, the better you can prevent long-term damage and long-term functional problems.

That happens here. But the difference with the axial spondyloarthritis is we really don't have great data that says that the treatments that we have, as good as they are at reducing the symptoms and the pain and the impact of the disease, we really don't have great data that shows that they affect the progression of the disease. But what does that mean? What it means is it changes the way in which you look at the treatment paradigm or the sequence of treatments, because the initial focus is not on, "Let's stop this because we're going to have more problems later." It's more on, "Let's make it better now," okay? So, what does that mean? It means that, even in 2023, the first line of treatment for this disease are non-steroidal anti-inflammatory drugs like naproxen, diclofenac or Voltaren, ibuprofen, any of those. And because they're very effective for pain, they're very effective at reducing some of the inflammation that's causing the pain, they're very inexpensive and, for most people, they're very well tolerated and don't have a lot of side effects. And if they solve the problem, if people are better, if their disease is better, they feel better, they're more functional, they're less impacted, then that's all you need to do. Only when people don't do better do you move on to the next step, which are the biologic therapies, the same kinds of things that have worked in rheumatoid arthritis. They work here, but we just don't go there as early because we don't often need to. That's different than in rheumatoid arthritis where, at this point, non-steroidal anti-inflammatories like we might use here, are never the only treatment you would give someone because they don't stop the progression of the disease and we know that we can't. Here because we don't know that we can stop that progression, there isn't really an impetus to go to a more expensive, potentially more dangerous drug with more side effects because there's no advantage to it.

There's a little bit of data coming out that shows that with long-term use, some of these biologics may slow how quickly people progress with this disease, how much damage they get to their spine, but it's not clear that it changes it enough to warrant the medication for a long period of time.

Melanie Cole (Host): So then, speak a little bit about some of the things that go on. You're speaking to other providers and I've heard that undiagnosed depression is common. And you mentioned that this is more prevalent in women, so you know, that would seem to follow. Can you please speak to other providers about when they are recognizing this particular condition, the comorbidities, the things that go with it because it can be delayed in diagnoses, which can be very frustrating for patients? Maybe they can't work, their quality of life is affected. Speak about that aspect, that psychosocial aspect of this.

Dr Eric Ruderman: That's a great question and it's really important here. It's actually very important in a lot of our diseases, but significantly here. And what we've learned is that actually in rheumatology, it's very interesting, if we look across the disease spectrum, the people we take care of, pretty much everything we treat, about 25% of people have some degree of pain that isn't inflammation-driven. There's a lot of depression. There's a lot of depression because they don't feel well, they're functionally limited. And so, that's a big comorbidity and that can actually sort of make the symptoms worse. And so, we have to address that.

But there's also the second issue of non-inflammatory pain. Sometimes what we know, if it's isolated and it's by itself, we often call it fibromyalgia, central pain, there's a lot of terminology for it, but why it's important is that that kind of pain isn't going to get better with the kinds of things that we use to treat inflammation. The non-steroidal anti-inflammatories don't help. The biologics don't help that. And so, sometimes there's this thought that like somebody's got this disease, you're treating them, they're doing okay, but they're not as good as you want. They're still having a lot of pain. They're still having a lot of difficulty with function. And so, the initial instinct is, "Well, let's just change their medicine. Let's try different medicines, see if it works better." But it turns out that that's not going to help. What you need to do is address this non-inflammatory pain. And there are other things that help with that. Things that we often use for fibromyalgia, like a drug called Lyrica or Pregabalin, or a drug called duloxetine or Cymbalta. There's just different things that can help that kind of pain, that work through different pathways. And sometimes people need both. Sometimes they need something to address the big picture inflammatory pain. But then, if they continue to have symptoms, sometimes they need this as well to get that other bit of it.

And to your point about why we need to think about this, the fact that there are women with this makes it very important because it turns out women do tend to have more of this non-inflammatory pain. It's not so much as it's depression, it's just a different kind of pain. And unfortunately, I think a lot of times people sort of blow it off and they say, "Well, you're just complaining" or "You're just whining" or "It just hurts." And the answer is no. It's very real pain. It's not that they're not making it up. It's just different pain. And so, you have to bring that in when you think about your treatment decisions and what you have somebody on. Maybe you kind of have to approach it from two different directions at the same time to get people under control. And when you do that, people do great. And the really self-aware patients get this and they understand it, and they'll come in and they'll say, "Listen, I was doing great, now I'm not, and it's not the inflammation, I can tell. It's that other kind of pain" or vice versa. And then, that helps to sort of figure out, "Okay, now what do we do to get that under control?" But it's really important to consider that and make it part of the conversation because if you don't, you're not going to make anybody better.

Melanie Cole (Host): I'm so glad that you went into that because it is such an important aspect for other providers when they're treating the whole patient and not just the particular condition. As we wrap up, Dr. Ruderman, and you know that we've discussed that there's a notable lack of awareness among primary care providers. I'd like you to wrap up by saying how you would like to change that and what else you'd like rheumatologists to know about treating patients with axial spondyloarthritis.

Dr Eric Ruderman: Well, I'll start with the second part first because that's the simplest. I mean, I think rheumatologists increasingly are understanding this. I mean, where there's a breakdown is rheumatologists, particularly people who have been at it for a long time as our understanding of the different variations in the spectrum of disease has changed, people may not keep up. And so, you have to sort of be aware that this is not a one-size-fits-all disease and that the ankylosing spondylitis of 30 years ago is just a piece of the whole puzzle. And you have to look at all the rest of that to make sure you find the right people, identify the right people, get them on the right treatment, and make the management decisions that you need to.

For primary care providers, it's a challenge because the first step is they have to even understand that this is a thing, that there is a disease. And for many primary care providers who went through medical school years ago, they say, "Well, there's ankylosing spondylitis, which is a disease that men got, and women don't get that. And so, I have a lady in front of me who's had long-standing back pain and I don't know what it is, but they can't have that because that doesn't happen." And the answer is it does. And so, for us as rheumatologists, I think there's just a big educational component. I spent a lot of time trying to go in and talk to the residents and the house staff and the med students, because you got to catch people early. And it's not that they need to know a lot, a lot about this disease, they just need to know that it exists and how to just recognize that it's a possibility, then send them to me and I can make the diagnosis as a rheumatologist and I'll treat them as a rheumatologist. You're not expected to know and treat everything as a primary care doc, but just be aware of it, that possibility.

And the simplest piece for them to think differently remember is persistent pain in a relatively young person that has that inflammatory quality, that has stiffness and pain in the morning that gets better with the movement, that should be the light bulb moment that says, "You know, this is someone who needs to get a closer look at it." And it could be a woman. It doesn't have to be just a man that has this, and think about that and then send them to me to, let me take a look and see if we can figure out what's going on.

Melanie Cole (Host): Thank you so much, Dr. Ruderman, for joining us today. You're such a great guest and this was so informative. Thank you again. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/rheum to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine Podcast for physicians. I'm Melanie Cole.