Differential Diagnosis in Nr-axSpA

Transcript: Sergio Schwartzman, MD: Centralized sensitization or centralized pain syndrome, as Daniel Clauw would call it, is probably the biggest challenge to us, particularly because this group of diseases is associated with enthesitis. I know that centralized sensitization is a very strong interest of yours, Philip, but can either you or Atul answer how you would go about objectively evaluating patients where that isn’t a differential diagnosis vs. inflammatory disease that is the enthesitis component?

Philip J. Mease, MD: As you alluded to, Sergio, it’s very tough. One of the things that we’re starting to move toward is the use of validated questionnaires that patients and physicians will fill out together, such as the Widespread Pain Index and symptom severity scale that was developed by Fred Wolfe, Dan Clauw, myself, and others. It was first published in 2010 and most recently updated in 2019. There are also a few questionnaires that have been used in other types of studies, including the painDETECT questionnaire and 1 called the FiRST [Fibromyalgia Rapid Screening Tool] questionnaire.

If you have an elevated number of responses in these questionnaires, then it’s suggestive that you have central sensitization. The most definitive way is not practical in clinical practice, and that is to do neuroimaging, fMRI [functional magnetic resonance imaging] scanning. There have been studies even with PET [positron emission tomography] scanning where you can see certain changes in the central nervous system that are consistent with central sensitization. But this is not practical for daily practice.

The other part is looking if there is any evidence of inflammation still going on. If the CRP [C-reactive protein] was originally elevated in the patient and now it is normalized, or if there was very active light up on an MRI [magnetic resonance imaging] scan and now it is normalized, that could be of interest in helping you understand how much you control the disease with immunomodulatory medicines. But even those have to be taken with a significant grain of salt.

For example, it’s not recommended that we do serial MRI scans looking for inflammation. It’s not recommended to always be doing CRP testing because oftentimes CRP is normal even in patients with very active inflammation. I’m afraid that you hit upon an area that we still are not quite there yet in terms of being able to accurately distinguish the presence of inflammation vs. central sensitization.

Sergio Schwartzman, MD: What about the use of ultrasound, Atul? You look like you’re going to jump out of your chair there.

Atul Deodhar, MD, MRCP: I was going to jump. Your question especially was about enthesitis. For enthesitis, Philip calls it sometimes enthesalgia, which is pain and tenderness when you press on these areas. I think the objective enthesitis I have seen is mostly in the heel, and that’s why the definition of enthesitis in the SS [Sjögren syndrome] classification criteria is in the heel. Patients who have central sensitization very rarely would have plantar fasciitis or Achilles tendon insertion area pain.

Again, some people would have it and very commonly, plantar fasciitis and at least tendon insertion pain can be because of obesity, being overweight and standing on your job. That also is not very specific. Rarely in these situations of patients with axial spondyloarthritis can you actually see evidence of inflammation by examining that area, and it is generally asymmetric. You can see 1 part of the Achilles tendon where it inserts literally bigger than the other side.

If you tap on their plantar fascia insertion into the heel into the calcaneum, they have tenderness more on 1 side than the other. That is, I would say, an objective evidence. Beyond those clinically, to differentiate between enthesitis because of an inflammatory rheumatologic condition vs. central sensitization is very difficult. Ultrasonography, as you rightly said, is 1 area where one has to be very skilled at that, and I do ultrasound myself.

I can find a needle when I’m doing joint injections into various parts, and I do hip injections and so forth with ultrasound. Having said that, the ultrasonography of enthesis is still an art, and a lot of education needs to go into that. There were certain parts of the human anatomy that are suitable to do ultrasound to find enthesitis. The axial skeleton is not 1 of them. Axial skeleton enthesitis, which is measure a part of the MASES [Maastricht Ankylosing Spondylitis Enthesitis Score] enthesitis tool, those are not very accessible or definitive whether you do ultrasound or even MRI scan for that matter, and that does not differentiate.

I just want to go back a little bit and about this discussion that Philip had about central sensitization and fibromyalgia. The difficulty that we have is that just because somebody has fibromyalgia doesn’t mean that they don’t have axial spondyloarthritis. You can have both and about 30%, 40% of patients have mentioned that’s 1 of the comorbidities. In that situation, if you have a patient who you know has fibromyalgia then you might be thinking, “Does this patient also have non-radiographic axial spondyloarthritis?”

In that situation, I would say that the bar is higher for us to show evidence of objective involvement of the musculoskeletal system in an inflammatory process. This is 1 of the difficulties in diagnosing, and why there is a delay in diagnosis. Rheumatologists are used to seeing swollen joints in the periphery. They are used to seeing fusions, synovitis, and so forth. Here, in nonradiographic axial spondyloarthritis, the area of interest or the joint of interest is in the spine, so you really cannot examine whether there is inflammation.

If somebody already has fibromyalgia and mechanical backache, then you have to look elsewhere to look for definitive evidence of inflammation clinically. One of those areas would be the heel and plantar fascia and other things like uveitis, IBD [inflammatory bowel disorder], psoriasis, and peripheral inflammatory arthritis again. That is 1 of the issues we face in daily practice, differentiating among fibromyalgia, central sensitization, and coexistence of nonradiographic axial spondyloarthritis or only 1 of them.

Sergio Schwartzman, MD: Thank you.

Transcript Edited for Clarity