Psoriasis mechanism of disease: Genetic, environmental, and lifestyle factors
Featuring George Han, MD, PhD |
Chief of Teledermatology System Medical Director for Dermatology Icahn School of Medicine at Mount Sinai New York, NY
, Andrew Blauvelt, MD, MBA |
Investigator Oregon Medical Research Center Portland, OR
| Published September 13, 2023
Hi, my name is George Hahn. I'm director of clinical research at Northwell Health in New York. It is my absolute pleasure to be joined today by Dr. Andrew Blauvelt, investigator at Oregon Medical Research center. He is a giant in our field and has been involved in pretty much every single treatment we have for psoriasis. So it's our pleasure today to be talking about genetic, environmental and lifestyle factors, well as comorbidities. And it's a big, heavy topic, but I think we have the right guests today to talk about it. Thank you for joining us today, Dr. Belvel. I'm happy to be here, George. So why don't we start out by talking about the genetics of psoriasis? Because our patients always come in asking us who they should blame for their psoriasis. And of course, they like to blame their parents. They like to blame their genes. But what really is the role of genetics in the development of psoriasis? Yeah, it's a great question. We do get it a lot in the clinic. I agree. And I'm going to start quickly by giving a caveat in that 50 years ago, the first genetic study was published in psoriasis, and it was done by danish researchers in the Faroe Islands. And actually, this year, the International Psoriasis Council is holding a meeting in the Faroe Islands to commemorate the first psoriasis genetics paper. And basically, those researchers, 50 years ago said psoriasis was a genetic disease. There was evidence of genetics in that local population, that island population. Over the years, it's been a pretty complex nut to crack, I would say. I haven't personally worked in it, but I have kept a close eye on it because I have family history of psoriasis. And so it's very relevant to me. My father had severe psoriasis. My sister has psoriatic arthritis. I have a brother with plaque psoriasis. So two of the five children of my father with psoriasis, fortunately, I have not had it, but it's come up a lot, and I know kind of the basics. And another key, I think, study in this area was done by Stanford, and it was twin studies. And in the identical twins, if one had psoriasis, 70% chance of the other identical twin having psoriasis. So that was pretty strong evidence. If there was no genetic component whatsoever, it would have been a random two 3% of the other identical twin, but it was 70%. So that tells me two things. There is definitely a genetic component, but it's not 100%. It's not what we call mendelian disease, right, where it's black and white. If you have the gene, you don't. We normally think of psoriasis now as having genetic components or there's susceptibility genes. Right. So there's a bunch of those, there's up to 70 or 80 of those genes now that have been identified that either confer a risk for psoriasis or confer some protection in some way. So I usually tell patients, to get to your question, yes, there's a genetic component. About 40% of the patients have a family history, but it's certainly not the whole story. So it's sort of like a combo of genes from the parents kind of coming together. And even if they don't have any family history, I still say it's probably genetic due to kind of the combination of genes they've gotten from their parents. So very complex, but definitely a genetic component running through it, but not the whole story. Right. There's a lot of environmental influences as well. Right. And so speaking to those environmental influences, there's been a lot of work recently, I think, in kind of unraveling. What are those environmental influences, those first steps that make the psoriasis come out in perhaps a susceptible individual. So can you take us through maybe your thoughts about that? Yeah, sure. So another thing I want to just say quickly is that some folks say that there's two types or flavors of psoriasis in terms of genetics, the genes that tend to run in families. Hla Cw six is the most common one. We see an earlier onset of that in a peak, like in the late teens and early twenty s, and then what we call maybe type two psoriasis, analogous to type two diabetes, it occurs, it peaks more in the early forty s. And those patients tend not to have a family history, and it tends to be more associated with metabolic syndrome, diabetes, hypertension, and so forth. So a little bit of a by incidence curve there in terms of whether you do have family history or not, things that we all kind of know as dermatologists. Right. Stress infections like strep throat, especially certain medications, classic ones would be lithium, interferon stimulators. So aldera cream can stimulate psoriasis locally. Interferon alpha, that used to be given for hepatitis infection. So there's a number of things there. For me, the most common things that I actually see of my career have been strep throat stress, cold weather, usually. So I usually tell patients any kind of stress around the body, whether it's emotional stress or physical stress from temperature or stress from a medication or an infection can trigger that immune response of psoriasis. Yeah, certainly we see that a lot, like there have been published reports about the influence of weather on psoriasis. Are patients always coming in about the stress? And sometimes you see some of the patients retiring and actually the psoriasis getting better and definitely a lot to it. Why don't we shift gears a little bit and talk maybe a little more about the comorbidities that are associated with psoriasis? I mean, you mentioned already metabolic syndrome, which is something that I think is coming up more and more in our discussions about psoriasis. How do you envision that metabolic syndrome, cardiovascular disease, psoriatic arthritis, playing into the role of psoriatic disease in general. Right. If anybody has been paying attention to this area, George, like you and I have, we know that the list of comorbidities of psoriasis has become quite long. Right. It's a little bit overwhelming, all the different associations with psoriasis. And a lot of times when I speak know in front of audiences, they get overwhelmed and they don't know what to tell patients or what to look into. And I understand that. And our time is limited. So I tell folks that you should, at the first visit, always mention to me the two most important ones, and that's psoriatic arthritis because it's the most common. Right. And it impacts your treatment choice. Right. You're going to choose a different treatment if joints are involved versus just skin. And patients need to know about that. Right. They just need to know of that connection. And I still find psoriasis patients every now and then have never heard that they are at risk for arthritis. It just is not right. That should be the very first conversation or first visit with a patient. And the other one, out of all the long lists that I always mention is heart disease. And the reason I do that, and I put it right up front, is that it can kill you. Right. The impact is bad. We have so much literature now on psoriasis as an independent risk factor for heart disease. And I think it's super important. And again, I kind of go back to my father. He had severe psoriasis. He had two heart attacks and two strokes before he passed. And this was before we knew about cardiovascular disease and psoriasis link. And it's very personal to me. So I'm going to be mentioning that to all patients because I think the literature also suggests if we make an impact with a skin, we can reduce the risk of heart disease. So those are the two main ones. But I'm curious to hear what you have to say about that. Yeah, I mean, I think this is a really hot topic, especially because we're starting to see all the pieces come together. Right. When you have the pathogenesis psoriasis, you see some of those same cytokines being involved in the pathogenesis of atherosclerosis. It kind of makes sense that intervening upon one will lead to the other. I think that the literature has been mixed, mostly because, at least in my mind, our studies haven't been big enough or maybe they haven't been in kind of an enriched enough population to really get a signal. Do you think we'll get there one day where we actually can tell patients confidently, hey, this is your psoriasis? Maybe here are some markers we can measure for cardiovascular disease, and here are interventions that can help you with both. That's a really good point. It's the ideal. Right, George? So if we can tell patients, well, if you go on this therapy and you get this response, you will have x amount of decrease in the chance for heart attack. I agree with you, we're not quite there, but there's lots of pieces of evidence in my view of this. We have large databases that have been out there for a while suggesting that tnf blockade reduces the risk of events. We don't have that same kind of data yet, quite for seventeen s and twenty three s. But we have very interesting kind of going right up to more recently data where the folks at NIH, Nahal Meta and Joel Gelfan, where they put patients on biologics for a year, and they actually measured the atherosclerotic plaques. Right. The lumen size of the coronary arteries. And in those studies, it was il 17 blockers, actually, that came out as the best class of drugs in terms of improving atherosclerosis in a patient with psoriasis. And so 13%, 10% reductions in atherosclerosis over the course of one year. So it's not events, it's not preventing heart attack and stroke, but it's strong evidence that we're doing positive things with our therapies. We're definitely on the right track with that. Maybe in just our last few seconds, if we can talk a little bit about your thoughts on mental health and psoriasis, do you consider that as a strong comorbidity? And how do you kind of envision that in your approach to your patients? It's another great question. Back in the day, about 15 years ago, I was at the university, we started one of the first multidisciplinary clinics in the US for psoriasis. And so, of course, we had rheumatology, right, and dermatology. But we decided to have psychiatry, too. So we had psychiatry, rheumatology, derm clinic, starting in 2006, one of the first of its kind. And to be Frank with you, when we would ask patients about their mental health, of course I'm depressed. Of course I'm anxious because I have psoriasis. And basically, many of them did not want to do the referral because they first said, well, if you can just clear my psoriasis, I think I would be fine. So there is a component of the disease just causing lots of angst and depression because they have the disease. And then I do think there's people with true depression that needs to be treated. Right. But I think the first thing is to kind of assume, I think practitioners just assume that quality of life is impaired and patients are likely to be scoring poorly on quality of life measures or high in depression scales and so forth. And so not to ignore it, to keep an eye to it. I know we're not psychiatrists, but, yeah, I keep an eye and listen to what the patients are saying, look for clues of possibly more severe depression, maybe suicidal ideation. I think, again, we're not experts in this area, but we can listen. And keeping an eye out for those clues, I think, is important for us to do, too. Not listening, so important. Taking care of our whole patient. And that's what separates a great doctor from a good one. And thank you for teaching us and bringing all these great points to us today. I really enjoyed the discussion. Thanks a lot. Church.
In this installment of Discourses in Dermatology, Dr. George Han, Director of Clinical Research at Northwell Health in New York, sits down with Dr. Andrew Blauvelt, Investigator at Oregon Medical Research Center, to discuss the genetic, environmental, and lifestyle factors that influence psoriasis. They also explore the comorbidities associated with psoriasis and how they play into the role of psoriatic disease.
The role of genetics in psoriasis
Dr. Han begins by asking Dr. Blauvelt what role genetics really plays in the development of psoriasis.
Dr. Blauvelt references the first genetic study published on psoriasis, spearheaded by Danish researchers in the Faroe Islands in 1963, which found evidence of a genetic component to psoriasis in the local island population.
He also comments on a key study examining identical twins that revealed strong evidence in favor of a genetic component to psoriasis.
Dr. Blauvelt notes that while there is a genetic component to psoriasis, it’s not a Mendelian disease. Rather, there are 70 to 80 susceptibility genes that have been identified that either confer a risk for psoriasis or confer some protection.
With those factors considered, he explains to his patients that while there is indeed a significant genetic component, it does not account for the entire picture of psoriasis. He estimates that approximately 40% of patients have a family history of the condition but suggests that even those without a family history may still have a genetic predisposition due to a combination of genes inherited from their parents.
To summarize, he reiterates that psoriasis is a complex condition with a genetic component with other factors also involved in its development.
A seminal study demonstrating the genetics of psoriasis was conducted by Danish researchers on the Faroe Islands in 1963
Twin studies have also revealed strong evidence in favor of a genetic component to psoriasis
Psoriasis is not a Mendelian disease, but is influenced by 70 to 80 susceptibility genes
While there is a significant genetic component to psoriasis, it does not account for the entire picture
Environmental influences on psoriasis
Dr. Han continues the conversation by asking Dr. Blauvelt about the environmental influences on psoriasis that may encourage psoriasis in susceptible individuals.
Dr. Blauvelt replies by giving more background on the genetics of psoriasis, explaining that there are 2 types of psoriasis as it relates to genetics. The first type is a result of genes that tend to run in families, with HLA-Cw6 being the most common. With this type, there is usually an earlier onset in the late teens or early 20s.
The second type tends to manifest in the early 40s, and those patients tend not to have a family history of the condition. Rather, this type of psoriasis tends to be more associated with metabolic syndrome, diabetes, or hypertension.
Dr. Blauvelt then begins delving into some of the well-known influences on psoriasis, including stress, infections like strep throat, and certain medications. He specifically mentions lithium and interferon stimulators, remarking that Aldara cream can stimulate psoriasis locally.
He comments that the most common influences on psoriasis he has seen in his career have been strep throat, stress, and cold weather. He advises patients that any kind of stressor on the body, whether emotional or physical stress from temperature, medication, or infection, can trigger the psoriasis immune response.
Influences on psoriasis can include stress, infections, and certain medications
Lithium and interferon stimulators can affect psoriasis
Cold weather can also trigger the psoriasis immune response
Comorbidities of psoriasis
Dr. Blauvelt comments that the list of comorbidities associated with psoriasis has become quite long and can be overwhelming for healthcare providers who are unsure how to counsel patients on this topic.
He describes his approach to speaking with patients and how he always discusses the 2 most important psoriasis comorbidities, psoriatic arthritis and heart disease, at their first visit. When discussing psoriatic arthritis, he explains that it is the most common comorbidity and will affect treatment choice, and that is an important facet for patients to consider and understand. In his experience, some patients with psoriasis are unaware that they are at risk for arthritis and thus it should be discussed early on.
Dr. Blauvelt also makes sure to discuss heart disease with his patients and emphasize the seriousness of it. He references the literature that is now available on psoriasis as an independent risk factor for heart disease and says it also suggests that the risk of heart disease can be reduced if an impact can be made on the skin.
He mentions large databases that suggest TNF blockers may reduce the risk of cardiovascular events but that we don’t yet have that same kind of data for IL-17s and IL-23s. He also references studies conducted at the NIH that put patients on biologics for one year and measured their atherosclerotic plaques. Those studies demonstrated that IL-17 blockers were the best class of drugs in terms of improving atherosclerosis in patients with psoriasis. While they don’t prevent heart attack and stroke, it’s strong evidence that these therapies are having positive outcomes.
The long list of comorbidities associated with psoriasis can make it overwhelming to counsel patients
The 2 most important comorbidities to discuss with patients are psoriatic arthritis and heart disease
Psoriatic arthritis should be discussed with patients at their first visit, since it’s the most common comorbidity and can affect treatment choice
Literature suggests that psoriasis is an independent risk factor for heart disease and that the risk of heart disease can be reduced if an impact can be made on the skin
Large databases suggest TNF blockers may reduce risk of cardiovascular events
NIH studies demonstrated that IL-17 blockers were the best class of drugs in improving atherosclerosis in patients with psoriasis
Mental health as a comorbidity of psoriasis
Dr. Han continues the conversation by asking Dr. Blauvelt his thoughts on mental health and psoriasis and how he approaches this discussion with patients.
Dr. Blauvelt references his involvement in one of the first multidisciplinary clinics for psoriasis in the United States that included dermatology, rheumatology, and psychiatry. When he asked patients about their mental health, they often reported they were depressed and anxious due to the condition. He found many were hesitant to be referred to the psychiatry clinic because they felt that if their psoriasis cleared, their mental health would improve, which demonstrates there is a component to the condition that can cause angst and depression.
He remarks that practitioners can assume quality of life is impaired for patients with psoriasis and that patients are likely to score poorly on quality-of-life measures and depression scales. He emphasizes that this should not be ignored and that it’s important to listen to patients and monitor for signs of severe depression and suicidal ideation.
Dr. Han concludes by agreeing on the importance of listening and caring for the whole patient.
There is a component to psoriasis that can cause angst and depression among patients with the condition
Patients with psoriasis will often have impaired quality of life and score poorly on quality-of-life measures and depression scales
It’s vital to listen to patients and monitor them for signs of severe depression and suicidal ideation