An expert dermatologist, George Han, MD, PhD, provides a brief overview of the pathogenesis of plaque psoriasis and reviews some common environmental triggers.
Brad Glick, DO, MPH: Hello and welcome to this HCPLive® Peer Exchange titled, “Changing Treatment Approaches in the Management of Plaque Psoriasis.” I am Dr Brad Glick and I am a board-certified dermatologist and a clinical assistant professor of dermatology at the FIU [Florida International University] Herbert Wertheim College of Medicine in Miami, Florida. Joining me today in this discussion are my colleagues, Dr Neal Bhatia, who is director of clinical dermatology at Therapeutics Clinical Research in San Diego, California. I am also pleased to be joined by Dr Erin Boh, professor and chair of dermatology at the Tulane University School of Medicine, New Orleans. Finally, joining us is Dr George Han, associate professor of dermatology at the Zucker School of Medicine at Hofstra/Northwell, in New York. Welcome everyone. Our discussion today is about the standard of care in the management of plaque psoriasis, along with the newer interleukin-23 inhibitor class of biologic drugs. We shall also focus on the long-term safety and efficacy data of these interleukin-23 inhibitors. Welcome everyone, and let’s go ahead and get started. I am going to start off with Dr Han. Briefly review for us the pathogenesis of plaque psoriasis.
George Han, MD, PhD: Thank you, Dr Glick, and thanks for having me. It is a pleasure to be here today. I think that is a loaded question, but we will try to summarize. Our understanding of psoriasis has evolved considerably in the last 20 years or so. It used to be thought of as classically Th1 [T helper cell type 1] versus Th2 [T helper cell type 2], and now we have started to really understand and appreciate the importance of the Th17 [T helper 17 cells] pathway, partly because of our research in psoriasis. We like to think of psoriasis, nowadays, as the activation and perhaps the hyperactivity of what should be normal inflammatory mechanisms. In that sense, there are some corollaries to autoimmune disease processes. The real question has become, what is the trigger? There are some candidates out there for that: LL37…TSO.
There are various things that have been found in patients with psoriasis that seem to act as an autoantigen, triggering some of the inflammation we have seen, but nothing is so consistent yet. What we do know, though, is that whatever the trigger is, there are probably multiple hits of genetic susceptibility, plus an environmental trigger that makes the patient have these activated dendritic cells that then are a source of increased cytokines and T-cell activation, proliferation, and expansion that eventually results in this proinflammatory cascade. We have found that, in this proinflammatory cascade, the key mechanistic pathway seems to be IL [interleukin]-23–induced activation of Th17 cells leading to increased IL-17, and finally to keratinocyte hyperproliferation. There are various aspects of this feedback loop, including immune-like cells and other processes that occur to create this long-term, chronic disease that we know as psoriasis and worsening inflammation.
Brad Glick, DO, MPH: Environmentally speaking, what would you say are specific triggers for psoriasis?
George Han, MD, PhD: We have classical triggers, like medications; certain medicines we have thought of traditionally as triggers for psoriasis. For a large number of patients, stress certainly seems to be one that kicks off their psoriasis. Of course, we know for certain forms of psoriasis, like guttate psoriasis, certain infections like streptococcal infections can be at fault. But I think for the vast majority of patients, it is just that at some point, the disease activity becomes great enough that it starts manifesting on their skin and tends to be rather progressive in a lot of patients.
Brad Glick, DO, MPH: Dr Boh, would you like to add any comments there?
Erin Boh, MD, PhD, FAAD: No; I think that covers it very well. I do think some of the other stressors are some of the same comorbidities we see with psoriasis—for instance, obesity. Then, once you start this inflammatory cytokine cascade, it spills over into other disease processes, which then puts added stress on your body. I think it is so integrated that we must look at psoriasis as a whole, and not just skin or just 1 aspect.
Brad Glick, DO, MPH: If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox. Thank you, everyone. Have a great evening.
Transcript edited for clarity.