The Changing Treatment Landscape of Plaque Psoriasis - Episode 1
As an introduction to a panel discussion on best practices using newer, novel therapies to treat plaque psoriasis, dermatology experts review what is now understood regarding the condition’s pathophysiology.
Andrew F. Alexis, MD, MPH: Welcome to this Dermatology Times® Viewpoints program titled “The Changing Treatment Landscape of Plaque Psoriasis.” I am Dr Andrew Alexis from Mount Sinai Morningside and Mount Sinai West in New York City. Our discussion today is going to focus on challenges in treating plaque psoriasis and the changing landscape of available therapeutics. Joining me in this discussion are Dr April Armstrong from the Keck School of Medicine at the University of Southern California in Los Angeles, California; Dr Andy Blauvelt from the Oregon Medical Research Center in Portland, Oregon; and Dr Erin Boh from the Tulane Medical Center in New Orleans, Louisiana.
We have a power-packed group of experts in psoriasis. It’s a pleasure to have all 3 of them here to share their thoughts and insights on the changing landscape of plaque psoriasis. To kick things off, I will turn to Dr Andy Blauvelt with my first question, which is a rather broad 1. Can you briefly review the pathogenesis of plaque psoriasis? What are the key immunologic and genetic factors that everyone should know? Go ahead, Andy.
Andrew Blauvelt, MD, MBA: Thank you, Andrew. Welcome to all the participants. Thanks for being here. When I describe the pathogenesis of psoriasis, I describe how it has changed over time because our understanding has increased over several decades. We used to think of psoriasis as a keratinocyte, mediated, or abnormal keratinocyte disease. That was prior to about 1980. That’s because when we look at the histology, the dominant thing we see are a thickened epidermis and activated epidermis. With the advent of the discovery of cyclosporin working in psoriasis and the advent of immunohistochemistry, we could actually immunophenotype cells within lesions.
Those things occurred in the 1980s. We realized that psoriasis was chock-full of immunocytes—white blood cells, T cells, macrophages, dendritic cells, and so forth. Our thinking evolved of it as more of an immunologic disease. Then it narrowed more to a Th1 disease when we have the Th1 vs Th2 disease paradigm that dominated the 1990s. Th1 cytokines are things like TMFL interferon gamma. The big discovery recently, though—the really important 1 for the field—is in the early 2000s a new type of T cell was described. Those were called Th17 cells, or TC17 cells, for CD8-positive T cells.
The reason they were labeled 17 is because they produced interleukin 17A as the dominant cytokine for this type of T cell. In those early years in 2000 to about 2010, psoriasis was identified as having a lot of Th17 cells, a lot of TC17 cells, and a lot of interleukin 17A being produced within skin lesions. That really was a major change because that led to new treatments being developed that target Th17 cells one way or another.
When we look at trying to target this new pathway that we think is the dominant 1 in psoriasis, we see targeting either interleukin 23 or interleukin 17. Those 2 are really closely related. IL-23 regulates proliferation and activation of Th17 cells. If we target IL-23, we see an effect downstream on Th17 cells and IL-17 production. Of course, we can target more downstream directly on IL-17, which also works wonderfully in psoriasis. That’s the overview of what we think of immunopathogenesis of psoriasis. Regarding genetics, I’d say it’s much more complicated. I don’t work in the field of psoriasis genetics, but I do keep an eye on it. We’re up to about 70 different genes that have been associated with psoriasis.
The key thing for the viewers to understand about genetics of psoriasis is that it’s not a monogenic disease. It’s not mendelian, we say, with autosomal dominant, autosomal recessive. It’s polygenic these multiple genes can play a role in susceptibility or in protection. They confer risk or protection. That’s why we don’t see psoriasis being easily tracked in families. It’s not half the children. About 10% of children of a psoriatic patient get psoriasis compared with about 2% of the general population. It is a risk factor to have a parent with psoriasis.
We do see monogenic or identical twins having concordance but not 100%. It’s about 70% of identical twins when 1 has it, and the other 1 has psoriasis. We do think of psoriasis as a genetic disease. It’s just not a classic 1 or an easily studied 1 because you have multiple genes contributing in different ways. We’re still in the early stages of fully understanding the genetics of psoriasis. We understand a lot more about the immunology now.
Andrew F. Alexis, MD, MPH: Thank you, Andy, for that very comprehensive answer. I like how you took it in historical context as far as our evolving understanding of this disease. That was excellent.