Updates in Understanding the Pathophysiology of Plaque Psoriasis

Alexa Hetzel,MS, PA-C: Andrea, how has our understanding of plaque psoriasis evolved, especially in regards to the pathophysiologies and this inflammatory cascade, and has it enabled more targeted therapeutic advancements?

Andrea Nguyen, PA-C, MS: That’s a great question, Alexa. When we talk about inflammatory cascade, it really alludes to some of the advancements that we’ve seen in understanding the pathophysiology about psoriasis. Historically, psoriasis was seen prior to the 1980s as really being an issue of hyperproliferation of keratinocytes, and it wasn’t until about 1982 that we identified that this is potentially a T cell–driven disease. From there we’ve really teased out a lot of the immunology that's associated with psoriasis and now we have evolved to seeing this really as being psoriatic disease. Like Jayme was saying earlier, you have psoriasis and psoriatic arthritis as potentially being manifestations of this pro-inflammatory state. And so, with understanding a little bit of the immunology aspect and understanding and teasing out some of the key cell players that involved from the 1980s we’ve really been able to tease out the key cells that are associated with driving this disease.

In the late 1990s, early 2000s, we were looking at potentially inhibiting TNF [tumor necrosis factor], and it’s been kind of a transition from there. In 2005, we identified the T17 cell line, and so from there, we've also teased out a lot of the involvement that interleukin-17, interleukin-23, and some of those driving aspects for this inflammatory pathway. And so, when you look at historic treatment for psoriasis, this is something that we used to treat many decades with things such as even arsenic. The current treatment landscape that we have today to treat psoriasis- we’ve made leaps and bounds in advancing treatments, not only from an efficacy standpoint, but as well, from a safety standpoint. It’s really only through the ability of being able to identify the key drivers of this inflammatory cascade that the treatments have been able to evolve to what they are today.

Douglas DiRuggiero, DMSc, PA-C: I love that original history that you brought up, because a really fun read, if you go find it in the New England Journal of Medicine, 1978, there were 2 Swiss rheumatologists who put an article in there that takes up a quarter of a page, it’s not even a full page, and they put 4 patients on cyclosporine. They had access to it because it was developed by Ciba-Geigy, although that company isn’t around any longer. They developed cyclosporine, and they’re based in Switzerland, and these Swiss rheumatologists put patients on it that had psoriasis and had joint disease and saw their psoriasis go away. They were the first, not dermatologists, but the first to propose that psoriasis was perhaps related to some type of T cell–driven disease because they knew the cyclosporine was a calcineurin inhibitor that impacted T-cells. That little article by Herrmann and Mueller, kind of, as you said, as we moved past into the early '80s, totally redirected the trajectory of this disease. So that’s a fun history to be reminded of.

Alexa Hetzel,MS, PA-C: Well, we used beg, borrow, and steal from other specialties, right? We used to use antirejection medications because we didn't have anything, or tar baths. Could you imagine a patient now going into the hospital for a tar bath? That’s crazy. We’re just so fortunate over the last just 5 years, 10 years, 15 years, to have so many more arsenal weapons to be able to treat our patients, like you said, Andrea, not only more effectively, but also a lot more safely.

Andrea Nguyen, PA-C, MS: What’s really interesting, too, is that we've seen this evolution within the past couple of decades where we have patients that we treat are familiar with what we used to use to treat, and they have seen the evolution in their own treatment and their own patient experience as far as what sort of efficacy outcomes they have, what type of tolerability they have, and their outcomes. So it’s been a lot of fun.

Alexa Hetzel,MS, PA-C: Go ahead, Jayme.

Jayme M. Heim, MSN, FNP-BC: When you were talking about tar baths you made reference to Goeckerman therapy, and I’ve had patients that have had psoriasis for years and they had Goeckerman therapy. When they talk about doing Goeckerman therapy, they literally weep. Tears just fall from their face because it was so traumatic for them. They were away from their family for days, in a tar bath, and then they were put in a sauna suit, and then put into light. It was very traumatic for them.

Alexa Hetzel,MS, PA-C: And especially because it wasn’t just a 1-shot deal. It’s not like it lasted that long. They would recurrently do this. It’s not like they got even a year of clearance, so it’s exactly what you said, it’s traumatic. So we’re very lucky to practice medicine now than we were 30 years ago.

Transcript edited for clarity