Pathogenesis of Plaque Psoriasis and Triggering Factors

Transcript:

Mark Lebwohl, MD: Hello and welcome to this HCPLive® Peer Exchange®, “Practical Approaches to the Management of Plaque Psoriasis.”

I am Dr Mark Lebwohl, from the Icahn School of Medicine at Mount Sinai in New York.

Joining me today in this discussion are my colleagues Dr Erin Boh of Tulane University School of Medicine in New Orleans; Dr Leon Kircik, also from the Icahn School of Medicine at Mount Sinai in New York; and Dr James Song, North Sound Dermatology in Mill Creek, Washington.

Our discussion today will focus on the currently available biologic options to treat plaque psoriasis. In addition, we will discuss some real-world cases and the practical considerations to help manage plaque psoriasis in these patients.

Let’s get started.

Dr Kircik, I’m going to ask you to start for us and briefly review the pathogenesis of plaque psoriasis. Discuss the role of genetics. What are the other triggering factors for psoriasis. Leon?

Leon Kircik, MD: Mark, thank you for inviting me to this panel. Our understanding of pathogenesis of psoriasis has been ever evolving. The more we are learning, the more we find out that we know less. In the old days we thought the Th1 pathway was involved in pathogenesis of psoriasis. Now we know that IL-17 is the major cytokine that plays an important role in pathogenesis of psoriasis. Then we thought that IL-17, coming from Th17 cells, and the Th17 cells are propagated by IL-23.

Now we know that IL-17 is actually coming not only from Th17 cells but from many other cells including mast cells, microphages, lymphoid cells, and you name it. There’s a huge different resource of IL-17 that comes in.

Then we found out that now it’s not only IL-78 but also IL-17F and IL-17C play a major role, because when we do a biopsy from a psoriatic plaque, we found out that those cytokines are also increased in those lesions.

What do you think, Erin? Do you want to add something else to that? James?

Erin Boh, MD, PhD, FAAD: I do think that pathogenesis circles around this, these inflammatory cytokines. But we have to also keep in mind that other things can trigger that immune response. Looking at the whole picture, each individual is a prototype of which cytokines are in higher levels than in others. That’s why we see our clinical response variances in patients with the same phenotype psoriasis. It’s going to unfold and be quite interesting as we start looking at the individual and which pathogenic cytokine they make. Our targeted therapy will become very exquisite in the future if we can figure that 1 out.

Mark Lebwohl, MD: Absolutely. I agree.

James Song, MD, FAAD: I would just mention that what’s interesting about psoriasis now is that we understand there’s this chronic feedback loop. Once it gets started, it’s really hard to shut that off. Even for patients who are well controlled on their biologic, when you stop therapy, those plaques seem to come back in the same areas. I think that speaks to the sense that there’s something more that’s going on. We’re understanding these resident memory T cells just lie resident in the skin. Even though they’re clearly invisible, you still may have those inflammatory cells there at the skin level. That will be really interesting, to see if we could get rid of some of those cells as well.

Leon Kircik, MD: That’s a really great point, James, that you brought up. That’s a hard issue: the scar of psoriasis, what’s going on underneath that we don’t see. The lesion is gone, but really it’s not. That brings up the issue of those several hundred dysregulated genes that we have in psoriasis patients, either up or down.

Now we’re getting some data with new biologics that actually these dysregulated genes are being regulated, and that’s why we’re seeing these longer clinical results that we see with the geobiologics that we have.

Transcript Edited for Clarity