Understanding Non-Radiographic Axial Spondyloarthritis - Episode 14
Sergio Schwartzman, MD: : Philip, I think we’ve touched on this, but I’ll ask it in the interest of being complete. How can we increase recognition and understanding of nonradiographic axial spondyloarthritis to ensure a more timely and accurate diagnosis? What needs to be done to shrink that number to what it is in rheumatoid arthritis, which is actually less than a year from symptom onset to diagnosis of the disease?
Philip J. Mease, MD: Education, education, and education.
Sergio Schwartzman, MD: Great answer.
Philip J. Mease, MD: So it’s just what we’re doing now. We’re trying to share our experience, as well as our reading of the medical literature, and sharing all that information with other clinicians. I think I know that both Atul and I, Tiffany, as well as you, are vitally interested in getting this information out to nonrheumatologists because, really, the patient’s journey begins there. There needs to be at least an “aha” moment going on in the mind of a primary care clinician or an orthopedist to say, “Maybe this could be an inflammatory immunologic disease.”
We need to think about getting the patient to a rheumatologist. So that’s really it. I think that’s so key. There are going to be issues, such as, should a primary care doctor bother to get an HLA-B27 [human leukocyte antigen B27 test]? Should the primary care doctor or orthopedist bother to get an x-ray of the pelvis, etc? All of these are potentially useful screening tools. But the bottom line is simply pattern recognition and getting the patient triaged to a rheumatologist. But in Tiffany’s case, look what happened.
She bounced around among several different rheumatologists and, even there, there was not a consensus. It wasn’t until that rheumatologist coming back from the European congress saying, “Okay, finally I get it. There is this entity out there called nonradiographic axial spondyloarthritis, and you’re a classic case.” I thought that was great. So they had become educated.
Sergio Schwartzman, MD: She fit the pattern.
Tiffany Westrich-Robertson: I was finally not a mystery.
Sergio Schwartzman, MD: So, Atul, to that point and speaking with Tiffany’s example in the background for us, differentiating these patterns between nonradiographic axial spondyloarthritis and the other more common diseases that rheumatologists see, what words of wisdom can you impart to us?
Atul Deodhar, MD, MRCP: This is what they are. This, of course, fellows learn during their fellowship, and the classic rheumatoid arthritis pattern would be bilaterally symmetrical. Small joints of hands and feet involvement—MCP [metacarpophalangeal joints], PIP [proximal interphalangeal joint], and MTP [metatarsophalangeal joints]—distribution of the articular is very typical. If somebody comes with that type of swollen MCP, PIP, and MTP, 9 out of 10 times it is going to be rheumatoid arthritis. Perhaps only 1 out of 10 times it might be some type of a viral arthritis. But it’s very different. The presentation is very different.
Psoriatic arthritis, another very common disease, and axial spondyloarthritis share several characteristics, and that’s the reason both of these belong to the family of diseases, as I said earlier, called spondyloarthritis—nonradiographic axial spondyloarthritis is part of the axial spondyloarthritis, whereas psoriatic is the peripheral spondyloarthritis. But they have very common clinical patterns with asymmetric inflammatory arthritis, lower limbs more than upper limbs, and large joints more than small joints.
We also touched upon enthesitis a little bit. Enthesitis is quite specific to the spondyloarthritis family compared with rheumatoid arthritis. In fact, enthesitis is more important than synovitis in axial spondyloarthritis and also in psoriatic arthritis to a certain extent. Dactylitis, which I believe you mentioned earlier, is very typical in spondyloarthritis. These are all clinical features that make you think that this is not rheumatoid arthritis. If somebody has got more enthesitis, it’s asymmetric.
If there is dactylitis, there is psoriasis, there is this backache that nobody has really figured out the cause of, and there is inflammatory back pain, then that is not rheumatoid arthritis. So the involvement of the skeletal tissue, how it is involved and when it is involved, is why I said earlier that to me it is way more important than jumping onto doing MRI scans. This is what I insist and teach my internal medicine residents and fellows of the university.
The other important clinical difference…despite rheumatoid arthritis and axial spondyloarthritis both being inflammatory arthritides, one leads to mostly bony destruction, which is the work of arthritis, whereas psoriatic arthritis and axial spondyloarthritis have not only joint destruction but also new bone formation. There was a lot of research into this, and I think that boils down to the enthesitis part.
The new bone formation that we see in psoriatic arthritis and axial spondyloarthritis is mostly occurring as enthesitis first. The enthesitis starts with the mechanical trauma, with infection, with gut permeability changes, or all these other things. There is a lot of research being done in the microbiome and how the patients with axial spondyloarthritis have dysbiosis. So the gut problems or the mechanical trauma, as well as the infections, lead to the enthesitis.
That leads to a different type of cytokine milieu, mainly the prostaglandin E2 and the IL-23 [interleukin-23], IL-17 [interleukin-17] axis, which is very different than the axis that you see, the cytokine axis in rheumatoid arthritis. The prostaglandin secretion leads to the vasodilation and then efflux of the cells from the bone marrow near the enthesitis. There is a very classic prolific inflammatory response that you see in these patients with enthesitis. This inflammatory response then ultimately leads to the mesenchymal stem cells, which are also there in the perientheseal area.
But mesenchymal stem cells proliferate, and mesenchymal stem cells become osteoblasts, and osteoblasts make new bone. So the new bone formation is all linked to the different cytokine milieu that we see in spondyloarthritis compared with rheumatoid arthritis. That’s the difference between these 2 pathological levels: how inflammation can lead to joint damage as well as inflammation can lead to new bone formation.
Sergio Schwartzman, MD: Thank you.
Transcript Edited for Clarity