Derm-it Trotter! Don't Swear About Skincare.
Feeling frustrated or overwhelmed with everything skin? Does the skinformation overload make you want to swear about skincare? Join Dr. Shannon C. Trotter, board certified dermatologist, as she talks with fellow dermatologists and colleagues in skincare to help separate fact from fiction and simplify the world of skin. After listening, you won’t swear about skincare anymore!
Derm-it Trotter! Don't Swear About Skincare.
Itching for Answers: Understanding PN Inside Out
Dr. Shannon Trotter sits down with Dr. Shawn Kwatra, a leading expert on chronic itch, to shed light on prurigo nodularis (PN)—a painful, often misunderstood condition frequently misdiagnosed as psychological.
Dr. Kwatra explains that PN is driven by a systemic inflammatory cycle between the immune system and nerves, creating an itch patients describe as worse than pain. He shares new insights into diagnosis, mental health impact, and cutting-edge treatments, including two FDA-approved biologics—dupilumab and nemolizumab—that offer real relief.
This episode brings awareness, compassion, and hope to those living with PN—and to the clinicians working to better treat it.
any of these types of skin lesions nodules, but also smaller bumps and some excoriations from scratching. And when we looked in the bloodstream of these patients, we found there's rampant inflammation in their bloodstream. So, even though there's skin lesions, it's actually, I think, a systemic disease. You also get a comprehensive metabolic panel to make sure there's no liver or kidney dysfunction. You can get a thyroid to make sure there's no thyroid disease as well. The macro of what you're seeing is that patients are scratching. This is an itch-scratch cycle, but what I call the micro-itch-scratch cycle.
Speaker 2:Welcome to Dermot Trotter Don't swear about skincare when host Dr Shannon C Trotter, a board-certified dermatologist, sits down with fellow dermatologists and skincare experts to separate fact from fiction and simplify skincare. Let's get started.
Speaker 3:Welcome to the Dermotrotter Don't Swear About Skin Care podcast. Today I've got a special guest on here, dr Sean Quatra. He's a board-certified dermatologist and the Joseph W Burnett Endowed Professor and Chair of the Department of Dermatology at the University of Maryland School of Medicine. He has over 300 publications and is a global leader in everything itchy, especially chronic itch. Welcome to the podcast, sean.
Speaker 1:Shannon, thank you so much for having me on today.
Speaker 3:We love having you here because we know anything itchy is right up your alley. One of the things that I really wanted to talk more with you about today is something that we call prigonodularis. That you know all too well, but some of our audience members may not even know that this is actually a clinical diagnosis or something that we treat in dermatology. Do you mind kind of explaining what paragonodularis is?
Speaker 1:Sure. So you know the word parigo just means itchy bump, and so now actually, the diagnosis paragonodularis is really wide encompassing. It can be a patient that presents with nodules or smaller bumps, papules or excoriations, and all you have to have is chronic itch for six weeks or longer. Any of these types of skin lesions nodules, but also smaller bumps and some excoriations from scratching. So it's actually incredibly common. Our group did some of the first studies on the population level incidents and found that it was a few hundred thousand people, but every year it keeps going up. And family medicine, internal medicine, nephrology, liver docs everyone's seeing these types of patients, and so I actually think that the disease is totally under-recognized and that it even could affect millions of people every year. Every doc is seeing these patients. Whether they know it or not, they're seeing these patients. You guys are all seeing these patients and super easy to make a clinical diagnosis biopsy not needed.
Speaker 3:And so you talked a little bit how it presents and sort of that. It can be lots of different presentations. A lot of people think it just has to be bumpy, but you described it can also just present as scratch marks or excreation marks. How do you most often see prigonodularis present in the patient and what are the symptoms I mean beyond maybe obviously itching, which might be quite obvious?
Speaker 1:Yeah, the itch is definitely the most dominant feature that leads to sleep loss and quality of life disruption, but oftentimes these lesions also sting a lot, they're painful and there's many different manifestations. Usually you see nodules or bumps on the upper and lower extremities. We did a study that showed that these are the most common areas where you develop these skin lesions. But it can happen anywhere on the body where you develop these skin lesions, but it can happen anywhere on the body. What's sad is sometimes patients are labeled as having itching. That's due to psychiatric factors.
Speaker 1:There's a term excoriation disorder or I really don't like this term and I don't think anybody should use it, but it is an ICD-10 code ICD-9 code neurotic excoriations which I think is not respectful of patient. But many of these patients who actually have prionage lyris have been inappropriately labeled as having their itch be all in their head. And I've seen these patients and the number one question to ask them is are you actually itchy? And if patients are itchy, then they warrant therapy with one of our multiple FDA approved therapies now for this condition and many more that are coming along, and I personally had many patients who for 10 years or more thought that it was just all in their head. They were very itchy, they got treated and then they were totally clear and I made it my mission to always talk about this that we can't label people, as you know, having psychiatric related itch. We have to treat them. Itch is really on this neuroimmune axis and it's worth it to try therapy One of our new safe therapeutics that we have approved for this condition.
Speaker 3:I really like that you highlight that because I think you're right. We see this a lot in patients that come in. You know, and you probably see this in patients multiple times a day with dealing with so many patients with paragonodularis. But they'll say, yeah, you know, they've told me I'm crazy. I've been to multiple doctors. Nobody seems to be able to figure out what I have.
Speaker 3:And I think that awareness that you talked about, that people just put this on their radar, that this is a true diagnosis and the downside is, as you talked about the mental health aspect, is just having itch for that long. Imagine the stress and anxiety or even depression it might cause a patient. And so, yeah, there is that connection to mental health. But exactly right to highlight how it's not really all in their head. This is a true thing going on in their skin physiologically. That explains that itch, that the the bumpy part you know a lot of patients will ask about they'll, and maybe you can clarify this a little bit. Do you kind of look at this as a primary process of the disease itself or do you feel like, because of that chronic itching scratching, it gets created throughout the process? Or is it a combination of both, because they're always asking how do you explain these bumps that are coming up on my skin?
Speaker 1:That's a great question, and oftentimes they're actually symmetrically located on the extremities. So there is a thought that there actually is a neural plexus and the origin of these lesions is related to those different points. But what we also know is that two-thirds of patients this is a study from our group are actually itchy, both in the nodules or skin lesions, but also in normal appearing skin, and when we looked in the bloodstream of these patients, we found there's rampant inflammation in their bloodstream. So even though there's skin lesions, it's actually, I think, a systemic disease process warranting a systemic therapy. And I think one of the biggest problems with the management of these patients is that sometimes providers stick with topicals only targeting these lesions for too long and not recognizing this is actually a systemic disease process.
Speaker 3:And that's fascinating because we were learning more and more about this in dermatology right in general, about the skin conditions we treat. We used to you know, not to use the cliche but I think they're only skin deep only to learn more about sort of this chronic inflammation and, like you mentioned, more systemic or widespread throughout the body. Now you mentioned that neuronal plexus component. Do you mind explaining that a little bit more for our listeners that are thinking well, what is he talking about? Nerves, like again, because some people hear that nerve component like again I'm not anxious about you know, or maybe I get anxiety from itching so much, but where does that nerve component kind of play a role for patients?
Speaker 1:Sure. So there's actually nerves that go all the way out to that outermost layer of the skin, the epidermis and the dermis. We call them thinly myelinated A-delta fibers and unmyelinated C fibers. Many of us learn this in neurology or anatomy. I think all those classes I struggled with having to memorize all the cranial nerves I don't know if you remember that.
Speaker 2:Oh yeah, oh yeah.
Speaker 1:I really struggled.
Speaker 1:I still remember being in the library in medical school going over them, but they are important.
Speaker 1:I actually thought they wouldn't be important, but they're very important to what we do as dermatologists because those nerves go from that outer layer of the skin to the dorsal ganglion, they cross over in the spinal cord and they go to the brain and that is how the impulse of itch is transmitted.
Speaker 1:And the macro of what you're seeing is that patients are scratching. This is an itch-scratch cycle, but what I call the micro-itch-scratch cycle is a variety of different immune cells that we have, like eosinophils and T-cells and basophils in the skin that secrete a lot of cytokines, like IL-4 and 13 or IL-31. They stimulate the nerves because their receptors are on there. The nerves release neuropeptides and the neuropeptides actually cause immune cells to secrete cytokines and you have this cycle, and so chronic itch and paragonidolaris is a combination of dysfunction of these immune cells and the nerves. And the nerves actually are the endpoint of transmitting itch, which is the debilitating symptom that the patient experiences. So your nerves are very central to the disease and in these patients you're trying to find a therapy that can tamp down on both the immune and the neural parties that are responsible for transmitting chronic itch.
Speaker 3:So fascinating too. I mean I think people again just think of it just being so simple. But the way you describe it, I think a lot of patients, as you know too, would put it on the same level of pain. You know where they've maybe had significant pain before, maybe an injury or surgery. And it's very impressive how people will just talk about, yeah, but this itch nothing compares to how impactful itch has been in my life. I mean worse than pain. I can remember treating patients with skin lymphoma when I was in fellowship and some of these folks itch to the extent of, you know, even contemplating suicide because of how terrible itching can be. You know, with itching you kind of talked about kind of that physiologic reason why we itch and again how it's a little bit different, you know, and prigonodular is, do you see some differences to with itching, with different skin types, kind of going along the spectrum of lighter skin to darker skin, and how itch impacts them maybe a little differently, and just the physiology of it.
Speaker 1:Yeah, no, it's a great question To start. Chronic itch, I absolutely agree, is incredibly debilitating and we did a study with our itch patients showing that a chronic itch patient has the disruption on quality of life equivalent to a patient who has chronic heart failure, who's had a stroke or is on hemodialysis. So that's very significant burden that our patients are experiencing. And I always ask patients what is the worst itch or the peak pruritus or itching that you've had in the last 24 hours at any moment, zero to 10? And that number, especially if it's a seven or higher, conveys severe itch, oftentimes inflammation in the blood. You know people are not sleeping well. That's a great marker in the blood. You know people are not sleeping well. That's a great marker.
Speaker 1:What we've also found is that itch can have different presentations in time. So we know, from atopic dermatitis and eczema in African-American patients, you can often have more bumpy or papular disease on extensor surfaces. Paragonagylaris in African-American patients oftentimes has more thickened lesions, more fibrotic lesions, almost even keloidal in terms of the degree of fibrosis. So it's very interesting, um, the significant skin thickening, um, so there's just a variety of different disease manifestations. Uh, we know the itch process is similar, but what's so special about paragonagularis is you also have the double whammy of not only having terrible itch, but also having these disfiguring nodules that can impair you psychosocially as well. It's really, you know, the worst of the worst.
Speaker 3:Yeah, I mean think about it, because you know people are staring at you if you see these bumps. I remember having patients come in with PN and they're constantly wearing you know sleeves to cover up their arms because they're embarrassed or they'll just get labeled a picker right, and lots of people are self-proclaimed pickers. But we know this is so much more than that and what our patients experience no-transcript patients more.
Speaker 1:It's a great question. So patients with prigonodularis have certain diseases that are more common, for example type 2 diabetes, and type 2 diabetes in particular, I think makes sense, because you have high blood glucose, you can have damage to the peripheral nerves and that can actually almost set off this itch-scratch cycle by having damage to the nerves that can then release neuropeptides that secrete cytokines from the immune cells. So type 2 diabetes is one of these common areas, but we know there's other things like even COPD, chronic obstructive pulmonary disease, hypertension, cardiometabolic diseases. We know that hepatitis C, hiv, are more common as well. Actually, our group did the first genetic study of paragonodularis patients and found that it's genetically encoded whether you're more likely to itch in general and develop skin lesions or nodules consistent with paragonodularis, or if you just have itching on normal appearing skin, and so that's why the workup for paragonodularis is exactly similar to the workup for itching without a rash. You're going to get a complete blood count to look at hematologic parameters. I also look at the eosinophil count always because that's a good indicator, if it's high, of good type 2 inflammation.
Speaker 1:You also get a comprehensive metabolic panel to make sure there's no liver or kidney dysfunction. You can get a thyroid to make sure there's no thyroid disease as well, and then in certain patients with risk factors, you can get a comprehensive metabolic. You can get, in addition to a comprehensive metabolic panel, you can get the hepatitis testing tests for HIV. Those are all things that may be associated with the disease. But what I think actually, and where I think the science is taking us, some of the science that we're doing is that in a prigonodularis patient you have inflammation that's in your whole bloodstream, and I actually believe that a lot of these diseases that are associated with prigonagularis can occur or worsen if the disease is untreated. So we actually found that patients with prigonagularis are more likely to subsequently develop chronic kidney disease and have renal failure. So I actually think there's a missing piece here.
Speaker 1:It's not just that these diseases are associated with trigonodularis or itching, it's also that the uncontrolled inflammation from this disease can then cause damage to other organs, and I think that's a paradigm we're exploring and we've done studies with both dupilumab and emolizumab showing that they can reduce systemic inflammation in these patients, and really looking forward to more real-world studies that looks at this more in depth as well.
Speaker 3:That's going to be one of the key points, you know, I think, for people to take home from our conversation, because that is something I don't think that association there is in the minds of most you know practicing primary care physicians or somebody, and even just the of most you know practicing primary care physicians or somebody where, and even just the dermatologists you know, to really think of this condition beyond what we've known and really just apply it like we have to other, you know, skin conditions we treat like psoriasis or hidronitis sepharitiva or things like that. I do think people are really, you know, look at this superficially so that systemic piece and maybe how it worsens other internal issues. Hate to say it, we try to get away from internal medicine and derm, but I just don't think we can. You know these things are intimately connected. People try to run, we do sometimes, but I think it's going to catch up to us, especially with PN.
Speaker 3:Now that we've talked a little bit, you know, obviously, about kind of how it looks, a little bit on the pathophysiology sort of the diagnosis to it, I wanted to dive in a little bit deeper and talk kind of about the broad spectrum, you know, of treatment and how you might approach somebody that comes in and you're thinking, yeah, you clinically have prigonodularis. Where do you kind of start and how do you look at the different tools that are available to us to really control this disease for patients?
Speaker 1:So I pretty quickly, when I'm evaluating these patients, can get a good sense of how severe their disease is, and I think everybody should be using clinical bedside markers and asking people about their itch. Again, zero to 10, what's the worst itch you've had in the last 24 hours? You get a number. If it's seven or higher, even five, you know that you're having pretty severe disease and you need to be in the systemic realm. I think topical steroids are always reasonable as an adjunct therapy. Phototherapy is a reasonable therapy as well, but they're just slow.
Speaker 1:So to tell you the truth right off the bat, I'm usually going. If people have more than, say, 20 or so nodules, lesions and an itch around seven or higher, I'm immediately going to one of our two FDA approved therapies. So we have both dupilumab, which is an IL-4 receptor alpha blocker that blocks IL-4 and 13, which we know are increased in these patients, and then also recently we've gotten the FDA approval of nemolizumab, which targets the itchy cytokine IL-31, and it's a blocker of IL-30 and receptor alpha. We're very lucky to have multiple agents approved for prigonodular. Shannon, if I'd asked you that 10 years ago, I don't think you would have thought that was possible, would you no way, not at all yeah.
Speaker 1:It's amazing, and so we have these two drugs that actually don't require regular laboratory monitoring. They're very targeted, much safer, so we've tried in the past like methotrexate as a diaphragm any of these agents. So we're very, very lucky and what I'm trying to do is make sure that we decrease the amount of time that our patients are suffering, cause still I see patients every single clinic, even earlier today have gone years just with topical steroids and been suffering before they get to start on these systemic agents, other agents that we should know about. There's some off-label studies on oral JAK inhibitors. I actually presented some data on oral provacitinib and also topical ruxolinib that are being developed for this. So exciting to have new options in the pipeline. And then there certainly are different off-label therapeutics.
Speaker 1:Some things that people like to do are inject steroids. I think that's reasonable, especially if you have less number of spots that you can inject the steroids. Injection or intralesional corticosteroids are more effective in PN than topicals because, if you think about it, there's this dead layer of skin at the top, the hyperkeratosis it's very hard to get through that and the epidermal acanthosis to get to where the action is lower layers, the epidermis and dermis, where you have a lot of inflammation, the acinophils T cells, fibroblasts, that are releasing these cytokines. So that's's the reason that topical steroids don't work as effectively and oftentimes you can do the intralesional therapies. But especially a lot of skin and color patients, you worry about hypopigmentation in those patients.
Speaker 1:So in general, topicals are a little bit more challenging depending on the particular agent. I go for one of these two new FDA approved therapeutics and then adjunctive therapies like narrow band phototherapy can be helpful. It's just a little slow, I think, but reasonable adjunctive therapy for patients who have trouble getting insurance approval can always consider, you know, methotrexate therapy or cyclosporine for a very short period of time. Again, these agents are very untargeted and not really needed in this current landscape where we have more targeted therapeutics currently.
Speaker 3:And from the standpoint I don't know if you get this question a lot, I feel like often patients come in they're like, okay, I know about these options, Are there any other natural options or things that you think are worthwhile? Or should I be watching things in my diet? Or is there a supplement you would recommend? And again, knowing not always that is the evidence as strong as what we have, obviously, for our clinical trials and approved drugs Are there any types of, you know, treatments in that sort of arena that you entertain or may offer to patients as an option?
Speaker 1:You know, shannon, I'm gonna give you a story. I recently tried a lavender spray. My wife she's also a dermatologist yeah, she was like there's no way this works.
Speaker 3:I was having a little thing, they were telling me, you just want to prove her wrong Sean.
Speaker 1:They were saying hey, this will help you sleep. And my wife's like what are?
Speaker 2:you doing what do?
Speaker 1:you get, and I was like, no, I'm going to try it. And it knocked me out. And from that moment on too, I was like you know what? We're going to be really super open to all sorts of alternative things and I've been. I've been telling patients all about turmeric powder, all sorts of things. Um, but no, absolutely. I think that there's a role for alternative therapeutics. We have a study where we looked at the gut microbiome and found some very interesting results in prognodular patients that we're going to be publishing soon.
Speaker 2:But the one thing I tell these patients is we want to limit processed foods.
Speaker 1:So what we think is going on is that gut microbiome is actually signaling and can trigger itch by signaling through the vagal nerve, and what we are finding is that there's a lot of these fungal species that are upregulated in praga nodularis patients, and what we think is that they're tied to food deserts and processed foods. So I tell all my patients if you can have a handful of blueberries and eat some spinach or other greens and I'm talking to myself also, because I love french fries every day You're eating chips, I'm eating chips, but I'm telling people to eat blueberries and spinach. I'm a hypocrite. But as so we know that those things will help, will they cure you alone? No, probably not. But of course those are great things that you can do that can help a lot.
Speaker 1:I think the unbalanced diet has caused so many problems. We can see, with the rise of the dry night, a spur of tea, but I think probably go similarly as well. Whatever we can do to make ourselves healthier overall. But is there one alternative therapy? That's magic bullet? Maybe we just don't know what it is yet.
Speaker 3:Maybe it's lavender. I was going to say for sleep we found out.
Speaker 1:You have to try it. Oh my God.
Speaker 3:I do love lavender a little bit, the essential oil thing. I don't always know if it'll knock me out, but it does. It is relaxing, I'll give you that. I'll give you that. We've talked more about kind of the medical piece, anything you recommend if somebody is suffering from pregnenitis adjusting maybe the mental health aspect of how it impacts their life that you typically employ into your treatment strategy.
Speaker 1:I think it's really important to get help if you need it and to ask that question. You talked a little bit earlier about suicidal ideation. You talked a little bit earlier about suicidal ideation. I was giving a talk and a dermatologist came up to me and they said they had treated one of these patients with something we all use, a triamcinolone. We made a medium potency topical steroid you know most dermatologists use this very often and they'd had some time to see the patient back and they actually did commit suicide.
Speaker 1:Oh my, and it's very tough hearing that.
Speaker 1:I actually have a lot of patients that see me, that put a lot of pressure and say, hey, if you can't help me, I'm considering to kill myself, and it highlights how severe this disease is, how much of an impact we can make.
Speaker 1:But it also, I think to your question, highlights how important it is that we ask patients and refer them to get care and someone to talk to and someone to evaluate them and have a good relationship with psychologists and psychiatrists in our area and can refer patients and let them know that there's a huge mental burden. If you're itching and you can't sleep, of course you know you're more likely to have anxiety and depression and then that can be tough to get out of. Even if we get the itch better quickly, it's hard to get out of that. So I think, having that level of empathy and asking I know that we're very busy in our clinics, but simple questions there's anxiety and depression scales. A simple check-in takes a few seconds but it is important, I think, to do that and also to make sure that we're being aggressive with therapy. I think that's very important as well.
Speaker 3:Yeah, I like how you talk about that because it is a very holistic approach I think that we have to take as dermatologists. You can't silo out, you know, I think, all the skin diseases we treat, the impact they have on somebody's life, whether it's at work or their ability to sleep, or just their mood, or, you know, the development of depression or anxiety. You know, I think that's something we have to take very seriously because I think you know it's their busy days and people sometimes gloss over that or our patients don't maybe recognize it. So for us to be able to pull that out, get them to the right place, to add that into their treatment regimen, that really shows how we're committed to really treating disease and the patient entirely. So really love that.
Speaker 3:You highlight that. And before we kind of end here, I did want to ask where do you think we'll be in 10 years from now? You know we already talked about where we were 10 years ago. 10 years from now, in the treatment of PM, where do we think we'll be, or what do you think is the most promising treatment advancement that'll come forth?
Speaker 1:You know, now that we have a pipeline, I think that's the hardest thing to have a validated scale, approved drugs, a design of clinical trials. We're going to see a ton of new therapies and the mast cell has actually emerged as being very important. It's unregulated in the lesions of these patients and we know the mast cell releases all these itchy mediators and I think PN is going to be one of those diseases where we have mast cell modifying drugs being approved. There's multiple in development targeting brutinine, tyrosine kinase, also triptase and CKIT. There's many different angles of targeting the mast cell. So I'm very hopeful to look at that. I also think many of the drugs that are going to be approved for atopic dermatitis may also go in for pyrogonadularis things like OX40 and OX40 ligand inhibitors. Many of the other new monoclonal tri-specifics I think could be great for paragonadularis as well. So I'm very, very excited about all of the new therapeutics and to see how this field develops.
Speaker 3:And maybe lavender spray right.
Speaker 1:Lavender spray. Maybe I might do a clinical trial on it.
Speaker 3:Well, you'll just prove your wife right. She'll appreciate that, like all of us wives out there do. Well, thank you so much, sean, for coming on the podcast. This has been great to really get this broad overview of PN really help people understand, I think, this entity a lot better. It deserves a lot more attention than it's received in the past and it's exciting to finally see that people are really looking more into it and really providing patients with relief.
Speaker 1:For our listeners out there. If they want to find you, do you mind sharing with how they can locate you? Sure, I'm on LinkedIn at Dr Sean Quattro, also Instagram and X, so feel free to follow me.
Speaker 3:Well, thanks again for coming on the podcast and stay tuned for the next episode of Dermot Trotter. Don't swear about skincare.
Speaker 2:Thanks for listening to Dermot Trotter For more about skincare.
