This transcript has been edited for clarity.
Stanley Cohen, MD: I am Dr Stanley Cohen and welcome to Medscape's InDiscussion series on psoriatic arthritis. This is episode five of the second season. Today, we'll be discussing the strategies for early diagnosis of psoriatic arthritis, as well as mimics of the disease and the various clinical patterns and domains of psoriatic arthritis. I'm very excited today to have as my guest Dr Dafna Gladman. She is senior scientist at the Krembil Research Institute at the University of Toronto. Dafna is well known by everyone in rheumatology for her tremendous efforts over the last few decades in helping us better understand the phenotypes of psoriatic arthritis, the natural history of the disease through her observational registry, as well as treatment responses that we see with our various new therapies in patients with psoriatic arthritis. It's a great honor to have her here today. And welcome, Dafna, and welcome to InDiscussion.
Dafna Gladman, MD: Thanks for having me.
Cohen: Now, happy to have you. I'm just curious, you obviously have a special interest in psoriatic arthritis and also lupus … [you've] done a great deal of work in lupus as well. What attracted you to psoriatic arthritis? What was your interest in getting involved in research in that particular disease?
Gladman: I was working in a small hospital in Toronto called Women's College Hospital, which was a center of dermatology. And the late Dr Ricky Schachter, who was the head of dermatology there, actually asked me to see patients that she was following in her psoriasis center that she said had arthritis and nobody was looking after them. And I did that while I was still in training. I would go there after work and see patients. And in the course of about 3 or 4 months, I saw about 40 patients with psoriatic arthritis who were actually quite severe. And I realized that what I had been taught about the disease was not quite correct and I set out to teach my teachers. And the only way you could do that is if you started an observational cohort and learned about the disease so that you could get some data to prove the point. And that's what I did, and that's how I got into it. Initially, I was just going to do one visit for the patients that came in, and then I realized that things were changing under my eyes. I figured I might as well do a longitudinal cohort and I set it up as a longitudinal cohort. It was set up on a protocol that was entered on computer, and eventually onto the web. And we've got over 1600 patients registered now in our psoriatic arthritis cohort. And then we developed a cohort for psoriasis without arthritis that we started in 2006. And we're following these people prospectively.
Cohen: That's fantastic. Having that longitudinal data really helps us better understand the natural history of the disease. Let's talk about the diagnosis. Psoriatic arthritis is a little more complicated than rheumatoid arthritis as far as heterogeneity. Let's talk about the different patterns of disease and what you've seen in your longitudinal registry as far as the presentation of psoriatic arthritis.
Gladman: There are two approaches to what you call the patterns. You know, the word "pattern" [in terms of psoriatic arthritis] was originally described by Moll and Wright in the sixties and seventies, and they described five different patterns: the distal joint disease, the oligoarticular disease, polyarticular that looks like rheumatoid arthritis, arthritis mutilans, and primarily back disease. However, what we've observed in our cohort and others have observed as well is that these patterns don't persist. Somebody may start with distal disease and develop polyarticular disease. Somebody may start with polyarticular disease and end up with oligoarticular disease. Some start with back disease only and then develop peripheral disease, and some start with peripheral disease and then develop back disease. In 2006, when we first established the GRAPPA recommendations for treatment of psoriatic arthritis, we realized that we really should be talking about domains. And the domains of psoriatic arthritis now include peripheral arthritis, which could be distal, oligoarticular, or polyarticular. And of course, arthritis mutilans could occur in any of those types of presentations. The next domain was axial disease. Then there's a domain of dactylitis, enthesitis, and then the skin and the nails. And the reason for considering all these domains is recognizing that the disease is not just musculoskeletal. We have to consider the skin disease as well, especially when we're talking about treatment. Of course in psoriatic arthritis, there's a substrate. The majority, 90% of patients, have psoriasis before the development of arthritis. And while the timespan may be quite varied, from zero (in other words, starting at the same time) to more than 30 years between the skin and the joints; on average, it's usually about 10 years. Now we've noted that the risk is actually linear. The risk continues throughout the lifespan of a patient with psoriasis. But on average, they develop it within the first 10 years. These are the important things to consider. And it's important that we look at these things when we make the diagnosis. And it's important that we look at the domains or assess the items that are included in the domains as we follow patients so that we can manage them properly.
Cohen: It's always fascinating when you see a patient in whom you have to search the body for one patch of psoriasis versus those who come in with a BSA … you know, a much [affected] higher body surface area.
Gladman: That's exactly correct. In fact, there was a study that came out, it's probably about 15 years ago now, from the Netherlands. They sent a couple of patients for, quote, consultations with twenty-three different rheumatologists. Some were senior, some were junior, and some were trainees. And it turns out that only about fifteen identified the correct diagnosis. And it turns out that the reason they didn't, mostly, is because they didn't undress the patients to look for hidden areas of psoriasis.
Cohen: For this 10% of patients or so who don't have psoriasis at the time of diagnosis, there are criteria, diagnostic criteria. Walk us through the CASPAR criteria and what your approach is to those patients who don't yet have psoriasis and how comfortable you are in making that diagnosis and initiating aggressive therapy if necessary.
Gladman: That's obviously a very important question. For the CASPAR criteria, the stem — in other words, what you need to have before you can even apply the criteria — is the presence of an inflammatory, musculoskeletal disease: a person who has either inflammatory arthritis, inflammatory back disease (spondylitis), or inflammatory enthesitis. If a person has one of these components, then you can apply the criteria. Now, the criteria are obviously psoriasis heavy. So if somebody has psoriasis currently, they get two points. If they have a personal history of psoriasis, they get one point. If there is a family history of psoriasis in either a first- or second-degree relative, they get a point. Now, if they have nail lesions, they get a point. If they have a negative rheumatoid factor, they get a point, but they don't get penalized for having a positive one. If they have dactylitis, that has to be present at the current examination or reported by a rheumatologist. And then if the x-rays show juxta-articular ossification, which I call "fluff," to differentiate it from osteophytes. So if they have current psoriasis, they get two; [for] the other points, they get one. They can only get one value for the skin. In other words, if they have current and past and family history, they only still get the two. And all you need is three out of the six possible points to be classified as having psoriatic arthritis with a very high sensitivity and specificity. So you can see that if you don't have psoriasis but say you have nail lesions and you have a negative rheumatoid factor and you have dactylitis, you certainly would qualify. If you have fluff on the x-ray in the area close to the joint, then you can classify as psoriatic arthritis, together with two other points. However, it's the clinical picture that helps us. So dactylitis is unique to the spondylarthritis group of diseases, particularly psoriatic arthritis. Sure, it could be confused with podagra. There are very few other reasons that give it dactylitis. So if a patient has dactylitis, it makes it a little bit easier; if they have distal joint disease, which is inflammatory, not bony but inflammatory, then that is helpful. If they happen to have peripheral joint disease and axial disease, that's helpful. If it's an asymmetric type of distribution, then it is less likely to be rheumatoid arthritis. These are hints that the patient may have psoriatic arthritis, not rheumatoid arthritis or osteoarthritis or other rheumatic diseases. Often we can tell the difference. It reminds me of my first patient that I saw with psoriatic arthritis. I was covering a professor's clinic the week that he died. A patient came in who was an immigrant from England. And he walks to the door, he sits down, and he says to me, "I finally got it." And I look at him and I say, "What do you mean, you finally got it?" He says that Professor Bywaters in England told him that he had psoriatic arthritis and he said to Professor Bywaters, "but I don't have psoriasis." [The professor] said to him, "You're going to get it." And so when he came to Toronto, he finally got it. But it was clear he had the typical deformities of a patient with psoriatic arthritis.
Cohen: Right. So again, rheumatoid factor negativity is one of the criteria, but we do know that rheumatoid factor can occur in about 10% to 15% of people over age 50. And a small percentage of people may have low levels of anti-citrullinated protein antibodies (ACPA). But it really is a clinical diagnosis. As far as axial disease, is it really very similar to what we used to call ankylosing spondylitis or what we now call radiographic axial spinal arthritis? [Can you] highlight the differences?
Gladman: The main differences are, number one, that it occurs at an older age in people with psoriatic arthritis. Whereas the classic radiographic axial spondyloarthritis occurs in the teens and twenties, psoriatic axial disease occurs in the late thirties, forties, or even later. The other difference is that there is less pain. Axial spondyloarthritis is characterized by inflammatory back pain. Patients with axial psoriatic arthritis often don't have a lot of pain. So that's another indicator that there may be a difference there. When you look at the x-rays, there is often asymmetry in the sacroiliitis, with one side being affected and the other not, or the score would be different between one side and the other, like one side might be two and the other might be four, and in general they are less severe. So if you took 100 patients with classic ankylosing spondylitis, a large proportion would have grade three and four. If you took 100 patients with axial psoriatic arthritis, a large proportion would have closer to two or two/three. The disease is less severe and then there's also a lower frequency of HLA-B27 [human leukocyte antigen B27]. There is an association with HLA-B8 in psoriatic spondylitis, which is not in ankylosing spondylitis. And there are a number of other genetic markers that are different between the two conditions. Interestingly, the interleukin (IL)-23 allele that occurs in ankylosing spondylitis is different from the IL-23 allele that occurs in psoriatic arthritis; even though they both have an increased frequency of IL-23, they are different alleles.
Cohen: That's fascinating … that's really interesting. I wasn't aware of those differences that you brought out. So let's talk about finding these patients, identifying these patients. We, in our clinic, see many patients now referred from dermatology. They're more much more experienced with our medications now for the more aggressive psoriasis. But when should the dermatologists send the patients over? I mean, what should be the trigger for them to say, "you need to see a rheumatologist"?
Gladman: So, the first thing dermatologists have to do is they have to go a little beyond the skin and at least ask the patients if they have any joint pain, any joint stiffness, any back pain or stiffness, at least to have a direction. And obviously, if they have any obvious deformities, they need to be sent to a rheumatologist. And as you know, there are now a number of screening tools that have been developed everywhere around the world, including one that we developed in Toronto, the ToPAS, that are very highly sensitive and specific for psoriatic arthritis. So dermatologists can administer these questionnaires in their clinic, and if a patient scores a high enough score on the questionnaire, they should be referred to a rheumatologist. My own philosophy is that patients who have joint pain should have the opportunity to see a rheumatologist at least once to determine whether they have an inflammatory or non-inflammatory arthritis. Because, obviously, the commonest form of joint disease in patients with psoriasis is still going to be osteoarthritis, but at least a rheumatologist should be able to distinguish and then decide whether a patient needs to be followed rheumatologically or whether a primary care physician can follow them together with the dermatologist. I think it's important for dermatologists to at least think about the possibility that a patient has a joint disease and refer people that complain.
Cohen: One of the biggest difficulties in clinic is when we do see these people, many times they're on medications for their psoriasis and their psoriasis is better and they're still having joint pain. And it's very hard to discriminate whether they have, especially with hand involvement, erosive osteoarthritis or severe osteoarthritis or whether it's psoriatic arthritis. I assume you have the same difficulties. And I'm just curious, what are your thoughts on how you try to work through that?
Gladman: So again, we look specifically for inflammatory changes, both looking clinically for swelling, looking for redness, and on x-rays; the x-rays do help us distinguish because erosions are not typical for osteoarthritis. And then we often discuss with the dermatologist whether or not another medication might be more appropriate. Some medications work better for skin, others work better for joints, but there are a number of medications that work just as well for both. And so we can address together what medication would be most appropriate for the patient. Sometimes we just need to add another medication. Sometimes even an NSAID is helpful, and occasionally adding methotrexate is helpful, even though methotrexate doesn't work as well in psoriatic arthritis as it does in rheumatoid arthritis. But sometimes adding it to another medication and to a biologic, let's say, it works. And as I say, sometimes a change in biologic would help.
Cohen: We have so many wonderful medicines for psoriatic arthritis now. And I think all of us do try to stratify the patients. I'll ask you the question as well: skin versus joints, it's a lot of skin. We might go IL-17, IL-23 with more joints. We stick with our old friends, the TNF [tumor necrosis factor] inhibitors and our new friends, possibly the JAK inhibitors. But where is methotrexate now in your clinic? Is it still initial therapy or have you moved on?
Gladman: We are limited by what the government lets us use, and most of the government and insurance companies in Canada insist on trying methotrexate and leflunomide before going to a biologic. But when we go to a biologic, then [we have] exactly the same considerations. If they have severe skin disease, we would go with an IL-17/23 [inhibitor]. If they have mostly joints, we might consider a TNF inhibitor if they have significant psoriasis.
Cohen: So we've only got about a minute left, but I'm just curious, Dafna … in RA [rheumatoid arthritis], we have a lot of efforts on pre-RA and whether we can prevent RA from developing. Multiple clinical trials are conducted with modest success. And what about it? Are there efforts? I know there's a lot of preclinical work, basic work, trying to understand why patients with psoriasis develop arthritis. Are there any clinical efforts to try to see if they can take a psoriasis patient who might be one at higher risk, with severe skin disease or whatever, and try to prevent them from developing psoriatic arthritis or is this a little bit too early?
Gladman: So, no, there is a study currently ongoing trying to use one of the biologic agents to, quote, prevent psoriatic arthritis. But as you know, it's going to take a long time and a large number of patients before we can actually solve that.
Cohen: This has been terrific. I've learned a great deal and I hope that our folks listening will as well. And so I want to thank you for being with us. It's great to have an expert like you with us. Thanks again, Dafna.
Gladman: Thank you.
Cohen: Thank you so much for joining us for episode five and I look forward to another great discussion in episode six.
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Cite this: Searching for Clues: Early Diagnosis of Psoriatic Arthritis - Medscape - Oct 20, 2022.