Alan: Hello, my name is Alan Simmons and it’s my pleasure to be on Psound Bytes™ today.
Kaleigh: And I'm Kaleigh Welch. We're here today to talk about comorbidities, also known as conditions related to psoriatic disease, some of which you may be familiar with and some you may not. 
Alan: Joining us for our discussion today is dermatologist Dr John Barbieri, who specializes in inflammatory skin diseases such as psoriasis, acne, rosacea, atopic dermatitis. He is an Assistant Professor at Harvard Medical School and the Director of the Advanced Acne Therapeutics Clinic at Brigham and Women's Hospital. His research is focused on exploring the role of patient reported outcomes to ensure the patient voice and their perspectives on their care is captured. He is a Co- Investigator of the “Prevention of Cardiovascular Disease and Mortality in Patients with Psoriasis and Psoriatic Arthritis Research Study”, also known as CP3, which is funded by the National Psoriasis Foundation.
Kaleigh: In addition to the CP3 study, Dr. Barbieri is the Principal Investigator for the “Smartphone Delivered Cognitive Behavioral Therapy for Adults with Psoriasis and Comorbid Depression Symptom Study” also funded by the National Psoriasis Foundation. I for one am grateful for your research efforts in this field.
Alan: So am I. Welcome Dr. Barbieri. Thank you for being here today. So I was diagnosed with psoriasis at 7 and psoriatic arthritis at 35, and I got to the point where I was almost walking with a cane. We know psoriasis is related to a number of comorbidities or in normal English that's a lot of other conditions that are related to it – like psoriatic arthritis, heart disease, diabetes, irritable bowel disease, and a whole lot of other things. Some of which we discussed in Episode 234 where dermatologist Dr. Chesahna Kindred. Can you provide an overview of why all of these diseases are related to psoriasis and is there any research going on that addresses these other conditions?
Dr. Barbieri: You bring up a great point that there can be other manifestations or things that go along with it and together this occurs for a couple of different reasons. The first is there can be shared, kind of pathways of inflammation that go on in psoriasis and these other conditions. For instance, with inflammatory bowel disease we often see elevations in these cytokines, these inflammation signaling molecules like TNF-alpha, and IL-17 and IL- 23. And these are some of the same kinds of inflammatory pathways that we can see if we look at the skin of someone with psoriasis. So sometimes these shared tendency towards immune dysregulation to certain kinds of inflammation going too much, can contribute to things like psoriasis and other related conditions like psoriatic arthritis or inflammatory bowel disease. In addition, when you have all this inflammation in the body from psoriasis or psoriatic arthritis, that inflammation itself can just make it so the body's not quite working in its tip top condition. This can cause metabolic dysfunction, and this may be one of the reasons why psoriasis and psoriatic arthritis are associated with conditions like diabetes and cardiovascular disease. That systemic inflammation can affect how our blood vessels work, how our cholesterol metabolism works, how our liver works, and can lead to other kinds of problems. Finally, there can be what we call maybe pleiotropy, which is there's a shared underlying kind of genetic microbiome or exposure, some kind of shared pathway, some factor that predisposes both psoriasis and other conditions. For instance, we know that psoriasis is more common in individuals who are overweight or obese. And of course, that can also be a contributing factor to other conditions like diabetes and cardiovascular disease. So that can be another way that certain things can become linked.
Alan: You mentioned cardiovascular disease and I'm very familiar with that. As a Co-Investigator for the CP3 study, what do you see as the primary cardiovascular issues that people with psoriasis have? 
Dr. Barbieri: The CP3 study, which maybe we'll have a chance to talk about a little bit later, which is led by Joel Gelfand at the University of Pennsylvania, and I'm fortunate enough to be a Co-Investigator together with him in that study. We're trying to understand how we can better prevent cardiovascular disease among those with psoriasis and what unfortunately we see is that individuals who have psoriasis, they have higher rates of having things like high blood pressure (hypertension), high cholesterol or hyperlipidemia, and diabetes. And of course, these can all be risk factors for things like heart attacks and stroke. And unfortunately, when we look at just the overall data, those with psoriasis have premature mortality. They die younger than those without psoriasis, and much of that is mediated by this associated cardiovascular disease. So this is a very important comorbidity condition that goes along with psoriasis that we need to really optimize how we treat and manage to prevent negative consequences from it.
Kaleigh: And Dr Barbieri, why do you think people who have psoriatic disease are more likely to go under diagnosed and under treated with cardiovascular risk factors? And what steps can be taken to address those issues? 
Dr. Barbieri: Unfortunately, although those with psoriasis are at higher risk of these cardiovascular risk factors, they as you point out Kaleigh are actually less likely to be screened or diagnosed for them. And part of this is an access issue. So when Dr. Gelfand and Arash Mostaghimi and I have looked at this question, we actually found that individuals who have psoriasis are less likely to have kind of a primary care doctor relationship and sometimes just people in the community. About a third of individuals who are seeing a dermatologist for psoriasis don't have a primary care provider. So sometimes we just assume that they're seeing us for psoriasis. I'm a dermatologist. I just assume they have a primary care doctor who's doing that stuff, but they may not. So one major issue is just access to primary care services, and we certainly have a growing primary care shortage in this country and that's a whole discussion of how we can improve that. Another issue is awareness and education. Many people think of psoriasis. even with all we've learned as primarily a skin disease. But as we discussed it can be associated with many other things, including cardiovascular disease. So it's very important that we raise awareness about this among dermatologists, rheumatologists, and other healthcare providers so that we can make sure that those when they present with psoriasis or psoriatic arthritis, that we’re having those conversations, that we’re making sure that they're getting appropriately screened and treated for cardiovascular risk factors. And we need better care coordination. I mentioned the many individuals with psoriatic disease don't have a primary care doctor. When they do, if I'm seeing them for psoriasis, we need to have good pathways and not fragmented care so that we can all work together and make sure that we're getting those things done. Because of course, I may not be an expert at lipid management or things like that, but I have colleagues who are, and being able to work together as an effective team for that individual with psoriatic disease is critical. And that's really what the CP3 study is all about. 
Kaleigh: Thank you so much for sharing that. As someone who has had psoriasis for basically her whole life and has dealt with comorbidities, I really only recently learned about the increased risk for cardiovascular health problems because of psoriasis. And so, with that being said, could you tell us more about the CP3 study you've spoken about, which is also known as the “Prevention of Cardiovascular Disease and Mortality in Patients with Psoriasis and Psoriatic Arthritis Research Study” and are those results so far promising?
Dr. Barbieri: So this study is really trying to get at that issue as mentioned before that many individuals may not be getting appropriately screened and may not have good care coordination to get those risk factors managed. So the study, the structure of this, is we’re taking just individuals and standard of care. We’re not trying to recruit them in a specific way, just individuals who come to see a dermatologist or a rheumatologist for psoriasis. We're having them get screened for risk factors so that in and of itself maybe as the interventions trying to standardize doing that screening. But what's really unique and special about this study is that those who have elevated risk of cardiovascular disease, who have a risk of greater than 5%, they interact with a care coordinator who provides some  counseling, who helps to coordinate care with their other health care providers to make sure that risk factors that are identified are addressed and treated, and then manage long term follow up with that person as well. So trying to bridge that gap between where someone is at the point of care with myself and other health care provider getting treated for psoriasis or psoriatic arthritis and making sure they get that screening and that treatment for those cardiovascular risk factors to address them. We previously completed a pilot study which we're very fortunate to get funded by the National Psoriasis Foundation to conduct where we did see some early preliminary findings of support that this model can be helpful in improving cardiovascular risk factors among those with psoriatic disease. And now we're running a larger more confirmatory trial with probably about 100 people in it who have elevated risk to see whether or not this intervention is able to decrease their cardiovascular risk scores throughout the course of the study and we’re optimistic that this is going to be a nice potential approach to bridge that gap in terms of going from we know that these people are at higher risk to actually getting the screening and the treatment that we need to prevent those complications of cardiovascular disease.
Alan: Dr Barbieri, I am so thankful that you are investigating all this. I have a very close interest in this. Another thing that I'm also curious about is calcium buildup. Now I've had calcium buildup on my neck, my thyroid, in arteries. I've had calcium buildup everywhere for quite a while. Can you speak to why this might occur? And once you discover that you have this problem, what can you do about it?
Dr. Barbieri: Yeah, this is a really important issue and this is one way to also look for elevated risk of cardiovascular disease. There's stuff like coronary artery calcium scoring is sort of a emerging technique as a way to try to identify those who are at higher risk. And what we know is that chronic inflammation, we've talked about how psoriasis is not just in the skin, there's systemic inflammation too. That chronic inflammation can promote what we call atherosclerosis, those plaques of cholesterol and other things forming on our artery walls and our body kind of clogging them up and calcium then can deposit there. Then the other thing is psoriasis, it's an immune disorder. There's immune dysregulation and that immune overactivity also can cause endothelial dysfunction. The cells that line your artery walls aren't working properly. And then we start to get again that atherosclerosis, that buildup of cholesterol and calcification on the walls that can contribute to heart attack and stroke. And then the second part of this, when you have issues of atherosclerosis, what can be done about it? So of course, just standard strategies that we use for prevention of cardiovascular disease, like statins and those kinds of treatments can be helpful. And there's also some evidence that trying to address that systemic inflammation, treating that psoriatic disease, the psoriasis or psoriatic arthritis, may help reduce systemic inflammation, may help reduce some biomarkers that are associated with atherosclerosis and may be one way we can modulate this problem. There's a lot of ongoing research. Nehal Mehta and Joel Gelfand are leading a lot of it, to try to understand through the treatment of psoriasis and psoriatic arthritis, can we help prevent or address some of these issues when it comes to cardiovascular disease.
Kaleigh: In episode 220, we spoke about Crohn's disease and ulcerative colitis with gastroenterologist Dr. Lisa Malter. A disease that we haven't touched on is non-alcoholic fatty liver disease, or NAFLD. What is NAFLD, the symptoms, and what's the connection to psoriasis? I've heard there's a higher prevalence of NAFLD among people with psoriasis. 
Dr. Barbieri: You're right. Those with psoriasis, they have high rates of metabolic dysfunction and conditions like non-alcoholic fatty liver disease. And this condition it's characterized by fat accumulation in the liver in people who aren't consuming necessarily alcohol. Sometimes you think of liver disease as being related to alcohol. This is sort of liver dysfunction that's not related to that. It usually happens in the state of kind of metabolic issues and it's an asymptomatic condition typically. People don't necessarily know they have it unless they're screened for it. As you pointed out, the prevalence, the amount of people who have NAFLD can be maybe even up to 50% of people with psoriasis may eventually develop this. And this again ties back to that systemic inflammation and that metabolic dysfunction, which are known risk factors for NAFLD in general. So we have these shared risk factors. And then once let's say someone does have NAFLD,  I mean obviously this is multiple disciplinary care. This requires not just dermatologists and rheumatologists, but primary care physicians, liver doctors, cardiology doctors, and it comes down to trying to address the systemic inflammation. So treating psoriasis may be helpful for this and then trying to address the metabolic dysfunction so you're trying to be healthy weight and diet, physical activity. Sometimes certain kinds of medications that can help with metabolic dysfunction. And then there are certain kinds of testing that can be considered in those with psoriasis, especially those who have metabolic syndrome or obesity, to try to understand whether or not someone has NAFLD because as I mentioned before, this is typically asymptomatic. People don't feel it. So unless you're looking for it, you might not notice it. And the population that's at elevated risk, it's an important thing to be thinking about.
Alan: So Dr Barbieri, I have to know, are we any closer to understanding the correlation between psoriasis and psoriatic arthritis? Because not everyone with psoriasis gets psoriatic arthritis. Why is it so closely affiliated with psoriasis and is there any research that might indicate the link between the two?
Dr. Barbieri: Yeah, this is a really fascinating question. There's obviously genetic overlap between psoriatic arthritis and psoriasis. There's common immune pathways that are involved, like IL-23, IL-17, and TNF alpha. So they have some shared mechanisms. I think the question is like, well, why is one happening in the skin and one happening in the joints? And I'm not sure we fully understand that. There's certainly a number of ideas around this. You know, psoriasis, sometimes there can be a phenomenon called Koebner Phenomenon where there's kind of a friction or injury can lead to a psoriasis spot appearing on the skin. And joints, they undergo a lot of stress. They're having to bear our weight of our movements and things like that, and maybe that stress on those tissues in the setting of someone who has predisposition to these kinds of inflammatory pathways might make something appear on the joints. But I think this is really an area of active investigation and try to understand exactly your question. Why do some people only have psoriatic arthritis? Some people only have psoriasis. Why do some people have both? There's certainly lots of things that overlap, but what are those unique factors that lead to one or the other. 
Alan: So with psoriasis and psoriatic arthritis comes pain and itch which can disrupt your sleep. I've heard that people with psoriasis are also at a higher risk for sleep disorders, such as obstructive sleep apnea, which is something that I have also personally dealt with. What sleep disorders could occur with psoriasis, and can you explain why this occurs?
Dr. Barbieri: So one kind of sleep disorder just can happen is just trouble sleeping, so kind of insomnia issues. Psoriasis and psoriatic arthritis that can be painful, it can be itchy. Those things can make it more difficult to fall asleep and stay asleep so they can lead to sort of classic type of insomnia problems or tiredness. And then there is some association between obstructive sleep apnea and psoriasis. A challenge with this kind of association is what mediates it? Is it related to chronic inflammation? Like maybe some of the cardiovascular disease things. Or is it maybe related to some underlying factors. We talked earlier about how obesity is associated with psoriasis, that's also associated with obstructive sleep apnea. So there might be some sort of shared upstream kind of thing that causes both psoriasis and obstructive sleep apnea rather than kind of one lean to the other. So that's sort of another area where we need some more research to try and tease apart how these things are related, but those are some ways where they might be, certainly psoriasis and psoriatic arthritis can absolutely impact sleep, to really meaningful ways.
Kaleigh: So you mentioned lack of sleep and we know that this can also impact psychological health. We also know that just having psoriasis places one at a higher risk for developing depression and anxiety. I personally was diagnosed with anxiety a few years ago, and I've recently learned that the connection between depression and anxiety and psoriasis may be due to shared pathways with the skin brain axis. Can you please explain why this occurs? 
Dr. Barbieri: Yeah, our brains we have hormones that get secreted when we're stressed and things like that, like cortisol. There are ways that our body, our skin, and our brain can be connected to each other. There’s obviously nerves that are directly connecting them. So things that are happening in the skin and the brain can impact each other. Obviously psoriasis and psoriatic arthritis, they can cause quite a bit of symptoms. And when you're having those symptoms, that in itself can lead to depression and anxiety. When you're worried about whether or not something's going to get better or get worse or these different things that might go along with it that can contribute to mental health, comorbidities, can impact our psychological health. So these things can be related in a lot of ways, and there's some interesting research from Ali Choi in Singapore where they looked at people with a variety of chronic skin diseases, and what they found is that those who have lower levels of resilience, which is sort of a psychological health thing, they have worse quality of life for the same degree of skin disease. If you counted up how much psoriasis or different skin diseases on their body. So our psychological health, our skin health, and our interpretation of both of those can be very closely linked.
Kaleigh: Thank you so much for explaining that connection. So like Alan, I was also diagnosed at a young age and I also have some of the related conditions we've been talking about. I was diagnosed with Crohn's disease at 8 years old. I have anxiety.  The list goes on, right? There's other stuff always seemingly around the corner. It really is a head to toe disease. So, in addition to the physical effects, one of my biggest concerns is the emotional load that comes with having yet another disease on top of psoriasis, such as psoriatic arthritis. I remember a couple years ago sitting in the doctor and them telling me, hey, you're pre- diabetic and just thinking “Oh, I can't add one more thing to the list. The list is full already.”  It's hard not to feel scared when something new comes along. And I'm sure there are others that feel the same way. So what do you say to your patients who now may have IBD, heart disease or any of these comorbidities we've been discussing? How do you help them navigate the emotional impact, maybe the anxiety of managing psoriasis, compounded by other diseases that may have this bi-directional effect? 
Dr. Barbieri: Yeah, this is again where this collaborative care is so important. Because I'm a dermatologist, I'm pretty good at skin disease things. I know a little bit about mental health strategies like cognitive behavioral and things, but I'm certainly not an expert at those kinds of techniques. And so working together with their mental health professionals, I think is so important because addressing the psychological health aspects of this is not only going to improve mental health, it may actually improve the skin disease side of things too.  There's evidence in psoriasis and also atopic dermatitis that just actually addressing, using mental health interventions can improve the skin disease too. So it's really critical, just like we talked about working together to address cardiovascular disease risk. The same thing is true of addressing mental health factors as well. And we actually have a study funded by the National Psoriasis Foundation, this mindset trial, which we're really fortunate to be able to be doing this pilot study right now. Looking at a smartphone based cognitive behavioral therapy intervention with also coach assisted to try to see if we can make it more accessible to people to get mental health services because we have such a huge challenge right now both from a cost standpoint and from a access standpoint being able to get access to mental services. So if we can find a scalable model that is low cost that you can easily get the people that can help to address some of these really challenging psychological health factors that can go along with psoriasis that could be, I think, incredibly valuable to those with psoriatic disease.
Alan: Well, I really appreciate your response on that. Anxiety, stress, multiple diseases. It's hard. I'm coming up on 42 years that I've lived with this. So it's been an interesting ride. I started way back in the day before there were ever biologic and I was using coal tar and all this other kind of stuff. So let's turn to what can be done. There's some research that indicates the use of biologics can positively impact risks associated with cardiovascular disease. Can you talk about some of that research?
Dr. Barbieri: Yeah I think this is as I was talking a little bit about earlier. A lot of this work has been led by Nehal Mehta and Joel Gelfand where they've looked at in randomized trials with a variety of different biologics on risk of cardiovascular disease. Or looking at biomarkers or looking at coronary artery calcification, vascular kind of factors. And in general, it's hard to show large effects, but I think there is some kind of aspects of these studies that are promising. That this strategy may be helpful, but this is definitely an area of a lot of ongoing research where we need to learn more about how to do this effectively, but I hope that over time we'll find some strategies that can help us both effectively treat psoriasis and address some of the systemic inflammation, cardiovascular disease risk at the same time.
Alan: And could the same be said about psoriatic arthritis? I have done a little bit of research into all of the scary little black label warnings about using systemic and biologic treatments. And we may have a lot of listeners out there that are scared about some of that. As far as the role of medications as opposed to dietary changes, can we actually manage our disease through just only our diet?
Dr. Barbieri: I think that can play a role. So we know that some of the psoriasis is associated with things like obesity. So addressing that can certainly potentially play a role and modulate disease severity. We, you know, we see associations between increasing weight and increasing disease severity. So that potentially can be a part of management. But I do think especially for psoriatic arthritis, which can really be progressive and destructive where if you don't adequately address it early on, it may be hard to address it later on. You know, making sure that whatever treatment we're doing is working and not necessarily being afraid of some of these treatments, which can be incredibly targeted now. Historically, the way we treated it with medicines is kind of just like suppress people's immune system in general. And now we have so much more targeted approaches that are really directed to the specific aspects of the immune system that are really dysregulated. They're not functioning properly in psoriasis and psoriatic arthritis and trying to get those to be a bit more normalized. So I do think diet that can be a helpful part of an overall treatment strategy for psoriasis and psoriatic arthritis, but especially for psoriatic arthritis, which can be really progressive and debilitating, it is important just to be thought of if we're doing something like that, is it actually working enough or do we need to maybe add something else to help with that.
Kaleigh: So with our discussion today, it brings up the question is risk a certainty? What can we do to reduce the risks associated with these comorbidities, such as, what we've heard today, we've talked about diet, but are there other actions that can be done?
Dr. Barbieri: Yeah, in some of  our preliminary pilot study we did as part of that CP3 study, for people who are at elevated risk of cardiovascular disease, starting a statin had a huge impact often on cardiovascular risk. And of course, we know that from more broadly in medicine that statins can really have meaningful effects in terms of preventing cardiovascular disease. And there's a number of other medications sort of now that we use for cardiovascular risk progression as well. But you know appropriately treating cardiovascular metabolic risk factors I think is really important for preventing cardiovascular disease, and that goes beyond diet. In addition, for some of these other comorbidities like mental health, making sure that we're asking people about it, that we're thinking about steps that we can take to address any mental issues, which I think again are going to feedback to skin and other parts of the body. So that's really important. And then for other comorbidities, I think looking for them and then addressing them when they're there. It probably doesn't make sense to try to, like proactively treat someone who has psoriasis on their skin and they're able to manage it with topical treatments to be like “we should give you a biologic that's going to prevent inflammatory bowel disease”. That's probably not a practical approach because the rate of it happening might not be high enough - if that makes sense. But I think just making sure that we're thinking about whether or not any of these comorbidities are there, that we're looking for them, and that we're addressing them early if they do occur.
Kaleigh: Thank you for sharing. You know, I think based on all that we've talked about today, we really can see that psoriasis is so much more than just a skin disease. And so how can we encourage people to realize that the body's defense system has gone rogue and treating the disease itself is key to controlling all of the aspects associated with psoriasis? 
Dr. Barbieri: I think you bring up a really key point which is in psoriasis, the immune system, our defense against viruses and bacteria, it's really not quite doing its job. And so it's going to cause problems that you see in the skin or the joints as the psoriasis or psoriatic arthritis, but there's a systemic inflammation. Theres other issues. So it is important to try to adequately, I think, treat disease not just because it’s bothersome, improves quality of life, but because it may also help address some of the systemic inflammation aspects of things. So we really do wanna be aiming for really true like clearance and good control of things. And fortunately now we have such incredible treatments that we’re often able to achieve that. So we should hold ourselves to a high bar in terms of our treatment expectations and aim for those.
Alan: It sounds like the future of psoriatic disease really is taking a holistic approach or looking at the whole entire body. I'm so glad you were here today, Dr Barbieri. Do you have any final comments or thoughts that you would like for our listeners to take away from all the things that we've talked about today?
Dr. Barbieri: I think one of the main things getting to your point about a holistic approach is that you know psoriasis and psoriatic arthritis, they're more than just the skin and the joints. It's important that we're being thoughtful of all the ways that they can influence someone's life, whether that be mental health effects, cardiovascular comorbidities, or other kinds of issues. And we want to make sure that we're working together as a team both in the healthcare system and outside of it to deliver really high quality and comprehensive care to those with psoriasis and psoriatic arthritis.
Kaleigh: Thank you Dr Barbieri for being here for our discussion about psoriasis and related conditions. I continue to learn daily new things associated with my chronic illnesses. And so the information today is really helpful for me personally and I know will help a lot of other people as well. The future sounds promising as we learn more about the connections between different diseases and the impact of treatment. I look forward to learning more about the success of the CP3 and the Smartphone Study.
Alan: And for our listeners, whether you're looking for treatment options, community, or tips to help live a more active, healthy life, contact the National Psoriasis Foundation by emailing our Patient Navigation Center at education@psoriasis.org. You can get free resources. You can get individualized recommendations, and answers to a lot of your questions.