Overview of Psoriatic Arthritis



Anthony M. Turkiewicz, MD: Hello and welcome to this HCPLive® Peer Exchange titled, “Biologics and Advanced Therapies in the Management of Psoriatic Arthritis.” I’m Dr Anthony Turkiewicz of Rheumatology Associates here in Birmingham, Alabama. Joining me today in this discussion are my colleagues: Dr Steven Feldman of Wake Forest School of Medicine in Winston-Salem, North Carolina; Dr Hillary Norton of Santa Fe Rheumatology in Santa Fe, New Mexico; and Dr John Tesser of Arizona Arthritis & Rheumatology Associates in Phoenix, Arizona.

We’ll start this discussion today with you, John. If you don’t mind, give a high-level overview of the pathophysiology of psoriatic arthritis [PsA]. Please bring up the unique role that perhaps genetics, environmental factors play in this disease.

John Tesser, MD: Similar to all of our systemic autoimmune diseases, we identify genetic susceptibility and then environmental hits that lead to the clinical development of these diseases. With psoriatic arthritis there have been more than 11 gene types that have been identified, and that’s as of 2011, that confer genetic susceptibility. And although we all look to HLA-B27 as being the most prominent one, it in fact is only one of many.

Interestingly enough, HLA-B27 is not associated with spondylitis and sacroiliitis and PsA, as of course it is in ankylosing spondylitis. Having said that, the genetic susceptibility and environmental factors need to be put into the context of site matters. With PsA, as we all understand it being a systemic disease not just arthritis, we can look to joint, synovium, but also skin and gut, and also the enthesis, which is the most prominent musculoskeletal site that grabs our attention.

The environmental hit of biomechanical stress on the enthesis leads to an outpouring of interleukin-23 [IL-23}. It’s the interleukin-23/17 access that drives this disease. Now with psoriatic arthritis as opposed to rheumatoid arthritis, we’re not looking at T- and B-cell interaction so much, which helps to understand why there are no autoantibodies that we’ve identified in the pathophysiology of the disease.

And yet, when we think about what happens, we see that IL-23 is very prominently involved, of course as I mentioned, in the enthesis and enthesitis, but also in the skin. For example, damaged keratinocytes release DNA that simulates IL-37 that leads to plasmacytoid cells releasing interferon, that in turn effects other plasmacytoid cells to release IL-17 to drive T cells to go to lymph nodes that come back to the skin, and then to drive the IL-17 pathophysiologic role in the development of the psoriasis that we see. And in the gut, we looked at dysbiosis that affects all of this.

As I mentioned, in the joints the target is the enthesis, and we see how that is important to release IL-23, and that leads to the whole chain of IL-23, IL-17 events. There’s a lot more to this that is very complex, but that gives us an overview about what’s going on outside of the cell.

Now, what’s interesting is how IL-17 affects what goes on inside the cell. We’ve been focused on intracellular signaling in RA [rheumatoid arthritis], where we see IL-6 and other gamma chain cytokines that will allow for the JAK/STAT signaling intracellularly to cause DNA stimulation for further cytokine production. But in this disease, we’re seeing IL-17 that affects the TRF/ERK intracellular signal in cascade and chain.

What is important to understand is that there is an analogy of how all of these systems work, but there are different players in the system that allow for the clinical development of the disease that we see, which is the psoriasis, the enthesitis, the arthritis, and when there’s the inclusion of the gut, we have colitis. This gives a rather broad overview of what’s going on.

Anthony M. Turkiewicz, MD: Thanks John, there’s definitely a complex interplay in our PsA pathophysiology. Moving on, when you think about disease burden and prevalence, particularly here in the US with psoriatic arthritis, variations perhaps in PsA based on gender, race, age, do they play a role in the prevalence? Hillary, can you give some insights into this please?

Hillary E. Norton, MD: Psoriatic arthritis affects approximately 1% to 2% of the US population, which is about 1 million adults, including about 30% of patients with psoriasis. There’s an equal prevalence between men and women, and the onset is generally between the ages of 30 and 50. But many patients remain undiagnosed for many years.

Most patients develop psoriasis first, but approximately 10% of patients will develop the arthritis first, leading to potentially further delay in diagnosis. Caucasians are more commonly affected, and psoriatic arthritis is less frequently reported in Asians, African Americans, and LatinX populations, but the distribution across the ethnicities has not been well studied.

Transcript Edited for Clarity

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