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- [00:03]
A
Welcome to season three of Derms on Drugs, a video podcast brought to you by Scholars in Medicine, the best educational platform for dermatology and provided at no cost to medical providers. Germs on Drugs is where cutting edge derm meets hit or miss comedy. I'm Dr. Matt Zyrus from Docs Dermatology and each week I'm joined by my residency buddies, Dr. Laura Fares from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh. And we use our 70 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be against your term and you have some fun listening. New episodes drop every Friday on Scholars of Medicine, Apple Podcasts, Spotify and other major podcast platforms. And I highly recommend you download. The Scholars in Medicine app has a phenomenal set of video education, has all of our episodes in full color streaming video. You can see the crazy places that Patton gourds from, and overall, it's the best educational content out there. Real pharma independent coverage of all of derm, supported by an amazing AI clinical consultant called AS Simon. So this week I am super excited. We've got Dr. William Damsky on from Yale, whose work I have been following for several years, really has been bringing to the clinic a way to help us figure out kind of which biologic or which therapy approach might be most useful for our patients. Also, a deep expert in granulomatous diseases. Dr. Damski, great to have you on the show. And let's start by having you tell us a little bit about your background. Where did you train? How did you get into derm path? How did you get into kind of the figuring out the, you know, which. Which people are going to respond to what. What's the story?
- [01:53]
B
Great.
- [01:53]
C
Well, thanks. I really appreciate you guys having me. I listen every week and it's really an honor to be here. So, yeah, so I went to. I did my MD, PhD at the University of Vermont in Burlington, Vermont. I subsequently came to Yale where I was on the two plus two research track and derm residency. Initially, I studied melanoma, biology, immunology, and although I really enjoyed it quickly as a derm resident, I realized I wasn't the one giving, you know, immunotherapy to melanoma patients, giving radiation to patients with advanced melanoma, and I realized that inflammatory derm was so interesting. And so really, during residency, kind of got pulled towards inflammatory diseases and granulomatous diseases in particular because I found that treatment was so variable and treatment was so difficult for these patients.
- [02:42]
A
Yeah. Let me summarize that into what many people outside the world of derm would say is, originally you wanted to be a real doctor. Then you found out that in dermatology, we just made the diagnosis and sent it to the real doctor. So then you had to. You said, well, I can't do that to go back to being a real doctor. So then you were like, okay, eczema and psoriasis and the heart stuff. When did you finish residency?
- [03:05]
C
2014.
- [03:06]
A
Okay. All right, so we had better. You had better treatments in residency than we did, but still not great treatments.
- [03:13]
C
Correct. Correct.
- [03:14]
A
Okay. And then. So how'd you start to get into the. So that's kind of a. Nor a great jumping off point. And so it explains to me kind of what you've been doing over the last few years of trying to help us figure out, because these eczema patients, we still. It's such a heterogeneous disease. Right. So. And trying to figure it out more effectively. You know, even the distinction between, is it eczema or is it psoriasis, which is sometimes really easy, but sometimes really hard. But then, even if it is eczema, is dupilumab going to work or not? So, well, let's. Let's get started. Sergeant Ferris, I think, is going to kick us off. Dr. Farris, what do you got?
- [03:57]
B
All right, so thank you for joining us. So I have one of your papers, actually, which just came out in the chad, which is clinical utility of immune biomarker staining of skin biopsies and psoriasis and eczematous dermatitis, A single center retrospective analysis. So, you know, this basically gets to what Matt was just saying. Sometimes it's hard to. You know, it's definitely hard to know what drug to treat our patients with. But even taking a step back, there are those patients who are like, is this really exematous dermatitis? Is this more psoriasiform, even with histology? Sometimes we don't really. You know, we still have challenges of, A, making the right diagnosis and then B, picking the right treatment. So.
- [04:45]
A
All right, first, I got to interrupt for a basic, basic question.
- [04:48]
B
You have to. Yes.
- [04:50]
A
So, Bill, one of the things that I think a lot of people don't get is that, like, the way that you guys came up decades ago with the fundamental descriptions of different diseases in Dermpath was you take a classic cases of this and biopsy them, and if you. It's clinically classic, what's the path look like. And so that whenever we see cases that are not clinically classic and we biopsy them, the expectation should be, it's not going to be obvious, like, what is this? So it, it sort of makes sense that the, you know, because it's always like, why do I never get back a biopsy that just says lichen planus? Because when it's obvious lichen planus, you don't biopsy it.
- [05:30]
C
Right.
- [05:31]
A
Is that a reasonable way to think about this?
- [05:32]
C
Overall, I think you really hit on a key point. I mean, if it's difficult for the clinician, it's likely, but not always going to be difficult for the dermatopathologist. And so as you guys are aware, there are, you know, you can list 10 features of psoriasis, you can list 10 features eczema. Histologically, when you see five that go for psoriasis and you see five that go for eczema, and you're thinking about, how do I sign out this report? It's not always as straightforward as we'd like it to be. So, yeah, I mean, if it's difficult for the clinician, it's going to be sometimes difficult for the dramatopathologist. And that's a lot of what, you know, during my dramatopathology training, sort of seeing that, that's a lot of what led me to pursue this work.
- [06:07]
A
Okay, all right, fairs, go ahead. Faris.
- [06:09]
B
That's. It's disappointing. I always hope dermpath has like the final answer, but I found the long later I get in my career, the less I biopsy anything, but particularly inflammatory
- [06:20]
A
stuff, you know, who has the final answer? Patton.
- [06:24]
B
That's true.
- [06:24]
A
That's the. Whenever we can't figure it out.
- [06:27]
D
Yeah, I don't know either.
- [06:28]
B
All right, so this is about a stain which you guys called rish, which is RNA in situ hybridization based biomarking. Biomarker staining. So what is a RISH Panel? It's basically four biomarkers. You're looking for RNA to interferon gamma. So that's a TH1 signal, IL13, that's your TH2 signal. And then IL17A and NOS2, which is your TH17 signal. So I sort of look at this as you're saying, like immunologically, what does this dermatitis look like it is skewing toward. Okay, so what you did here was a retrospective analysis of patients who had rish testing in 2024, 2025. And importantly, this wasn't like, here's a Bunch of undifferentiated people. We're going to risk test them all and then follow this and do this. So this is retrospective. Retrospective. So the clinician had to request it. So just to kind of confirm with you, you guys don't ever do this, like, ah, gosh, I don't know. It's kind of examinous, kind of. Sorry. As from, let's do risk testing and see, you're. You wait for the clinician to ask we.
- [07:40]
C
Yeah, that's correct. I mean, sometimes if it's particularly challenging, we'll make a note that, you know, this testing is available if desired, but we don't ever go ahead and work on our own.
- [07:50]
B
Okay. Okay.
- [07:51]
A
But that does tell us you're kind of pulling out the easy ones. So if it's like an obvious psoriasis or an obvious eczema, the neuroendotopic dermatitis, it's unlikely that anybody's going to ask for RISH testing. And it's unlikely that you're going to be like, oh, we should do risk testing. These are sort of, by definition, the hard to figure it out cases.
- [08:12]
C
Correct? Yeah, I mean, I mean, we love the easy ones and we love to sign it out as psorias or eczema. But if you're biopsying, it's probably going to be difficult for us in many cases. But, yeah, I mean, most of our contributors here in Denmark are aware that we offer this testing, and so they've kind of learned when to ask for it. But, yeah, to answer your question, we don't order it ourselves.
- [08:30]
A
And just before I forget, if. If our listeners want to send you specimens, is there somebody they can email to be like, hey, can I, you know, I want to send some of path to Dr. Damsky, who'd be the. Is there some. Is there an email address you can give us that's, you know who they could reach out to? A lab coordinator or somebody?
- [08:50]
C
Yeah, totally. Yeah. I mean, if you Google Yale Dermpath, you'll come right to our website. And right at the top of that page, there's a tab called Submission Instructions, and it has detailed information, including an email address of how to submit samples. And we get a lot of consults from external institutions, so we're very used to it.
- [09:06]
A
Okay, so just Google Yale. So if you listen to this and you're like, damn it, I want to start sending specimens for that, just Google Yale Derm path and you'll be able to figure it out. Okay, sorry, Paris, go ahead.
- [09:17]
B
That's okay.
- [09:18]
C
And sorry to interrupt, but just in case I forget, part of the reason we don't order it off the bat is these get built through patient insurance. And in general we've had good luck getting it covered, but we don't want to in case that doesn't happen. We'd hate to order it when the clinician doesn't really want it and have the patient, you know, end up with a bill that seems like it doesn't happen very often.
- [09:36]
B
Okay, helpful information. Okay, so in getting back to the study data, this retrospective study, so you, you collected the indication for the risk testing, the pre diagnosis and post to sort of see what changed and then treatment within six months. So basically looking at did diagnosis change and did treatment change change? Focusing on topical and systemic therapy. Okay, so among se at 119 patients who had the testing, 92 men, inclusion criteria. These people were average age of 52. I think kind of good point that, you know, that it's really, I find like among the adult dermatitis population that it can become the most challenging. Now I also don't see kids, so that might be a little bias. Okay, and of your 92 people, 77 of them had post risk follow up. And so you guys found that RISH confirmed the suspected diagnosis in about 47%, clarified the differential in about a third and led to a new diagnosis in 17%. And only about 4% remained unclear. So treatment recommendation changes occurred in over half, 58%. And in those among those 60% explicitly were attributed to being to Risch treatment or to the Risch test results. So mo re Rish, which seems like the reason why ev indicated most commonly to distinguish basically eczematous dermatitis from psoriasis when clinical or histologic impression was discordant. And so among the dermatitis patients, 68% had a change in treatment recommendation. Dupilumab and Jak inhibitors were the most frequent recommendation. Among the psoriasis patients, 71% had new recommendation and 70% of those were documented as being due to RISH. So, you know, the, that was sort of the, that was interesting. If I look at your result table, you can see that the majority of patients who had their, who had a treatment changed actually were improved. So among the psoriasis, you know, you had 10 that nine patients who started a new treatment, five of them improved, three of them did not, one of them worsened. And then among the dermatitis patients, you had 19 who started a new treatment, 13 of those improved and then three did not. But none of Them got worse. So, you know, interesting study. Looks like, you know, the test actually did impact care and it looked like, you know, clinicians followed it, which is important. And then it looks like, you know, people did often, you know, get better. So I thought that was, I thought it was interesting. So I think, you know, the limitations here where it's not a prospective study, obviously, so, you know, people had to request the test. It wasn't sort of an unselected series of patients. Have you guys thought about, are you planning to do like some sort of prospective clinical trial with this or, you know, what do you see as like, next steps?
- [13:08]
C
Yeah, it's a, you know, it's a really important question and thank you for bringing it up. I mean, you know, we have a lot of people ordering this test. A lot of other institutions are actually starting to offer for this testing and there's really was nothing in the literature about how this actually impacted care. And so Tara, who was a postgraduate or medical student in my laboratory, really dug into the charts and this is a very hard study to do practically, but really we wanted to see, like, how are people using this? Is it impacting care? And, you know, we didn't have a agenda going into it. We were just kind of curious. And so it was a learning experience for us. We thought we'd put it out in the literature for others that are trying to do this. You know, again, I mentioned insurance coverage and it's helpful, helpful to have something out there, I think showing that this is useful. It would be great to prospectively validate this. And we had discussed prospectively validating it, but we've actually been pivoting to a different non invasive approach that, you know, we can talk about if you want, that actually doesn't require a biopsy.
- [14:08]
B
Yeah.
- [14:08]
C
So I mean, the great are that we can do it with a biopsy. We can do it with a biopsy that was performed five years ago. But doing the staining is expensive, doing the interpretation is laborious and it's intrinsically low plex. So we can, you know, do four or five stains on a case and we can give some immunologic information. Like we really tried to drill down on the most important biomarkers, but, you know, the immune system is a lot bigger than four markers. And so we're looking to, you know, switch over to something that's sort of higher plex. And rather than prospectively validating this, although we'd like to, we kind of switched over to this new approach that we're working on. Oh, that's great.
- [14:47]
A
What's the new approach? Come on.
- [14:49]
B
Yeah. Is it scrapings or tape strips or. What are you guys looking at?
- [14:54]
C
Neither.
- [14:55]
B
Okay.
- [14:56]
C
Yeah, but. But, you know, we thought about those things when we put this together. So the approach that we've developed actually uses two detergents. So it's something that solubilizes the epidermis. So it's like two detergents with some other stuff in it. And you put a drop of this stuff on the patient's skin, and then you basically take a swab and you rub it for about a minute. And we've developed conditions where it solubilizes the full thickness of the epidermis. So it samples more deeply, we think, than curettage and certainly tape stripping. And then you get, like, a protein soup out of it. And we subject that to proteomic analyses where we can measure with absolute quantification all the different proteins that are in patient skin.
- [15:39]
A
So just for. What did you guys come up? Like, I've never heard of. It's. Intuitively, it makes amazing sense, and it basically sounds like a cult. You're doing a culture of your cytokines. Like, I know that's ridiculous on what you're actually doing, but like this. Did you guys come up with this idea of a way to do this?
- [15:59]
C
Yeah, we kind of pulled some things out of the literature. I mean, this is something we spent a lot of time thinking about over the last five years or so. And so we hit the literature, and we didn't use AI at the time. We probably would use AI now, and it probably maybe would have led us to the same place. I don't know. But yeah. And, you know, it took a lot of optimization to actually get it working well. But, you know, from, you know, at face value, it's really straightforward.
- [16:23]
D
How big is the area? And when you say it solubilizes the epidermis, does that leave, like, a little. A little erosion? A little scar?
- [16:33]
C
Yeah, it leaves a little erosion. So we've done this probably in over 800 patients so far.
- [16:38]
B
Oh, wow.
- [16:39]
C
And it's really well tolerated. I've had it done to myself more times than I can count. It's really. It's really pretty easy. And we optimize the conditions. So we basically get down right to the dermal epidermal junction. So why we tried for that was that we wanted to get the full thickness of the epidermis. We didn't want to leave a scar. We didn't want it to bleed one. It would make it easier. And two, we didn't want the, you know, the blood contaminating the samples that we're collecting. Collecting.
- [17:05]
A
This is the coolest. So first, you are speaking my language. You've done it to yourself a bunch of times. That is. That is the right way to go. Every.
- [17:14]
B
Every new drug should be tested. Every new intervention.
- [17:19]
C
What.
- [17:20]
A
What kind of solvents are you using? What are you using that you're dissolving the entire epidermis away?
- [17:26]
C
Yeah, I mean, it's really simple. And we use a combination of two detergents. These are detergents that are in a lot of cosmetic products. They're well tolerated. They're just at a little bit higher concentration and they're, you know, not applied gently with your hands in the shower or in the sink. They're, you know, rubbed with a Q tip.
- [17:45]
A
You know what you're. What you were making me think is, like, you put this stuff all over your face, rub the shit out of it. You could have, like a whole new version of chemical peel here.
- [17:57]
C
Right.
- [17:58]
B
So how many different proteins are. Can you. I mean, I like. So, you know, just for, like, listeners thinking about this, like the study I did, that's RNA that you're looking at, right? So that's what's being transcribed. But, you know, there's nuances to, you know, what, you know, transcription versus translation. The protein is like, what's there and active. So I kind of like this. It's also novel. Like, most of the tests that you do, really more look at gene expression or rna, not at the actual protein. How many different proteins are you looking at?
- [18:29]
C
Yeah, so for our panel that we're validating clinically, we look at 45 different proteins, okay. But we've actually done it with as many as 3,000 different proteins. I mean, the more you do, the more the cost is. And we think that we really actually only need like, 10 or 12 to do what we want to do with eczema and psoriasis. But they're part of this 45 cytokine panel. And I agree with you. I think the proteins are more important than MRNA. So, like IL13, IL17A, like, there's pretty good correlation between MRNA transcript level and protein activity. But for other things, there's not, like, TNF, io1.
- [19:01]
A
And for. For our listeners who are not scientists, who are not basic science people at all, cytokines are proteins. So, like, whenever we say so, protein could mean everything from filagrin and keratin to collagen. But IL13, IL4, IL31, IL17, Interferon. These are all proteins. So you're able to measure the actual. And that's so much more robust than kind of the idea of tapes. You know, Tapestry has been around for a long time and the whole thing, but it's very limited in what's going to get through the stratum corneum, man.
- [19:37]
B
So how about, like, patients who just have very undifferentiated disease and you're like, I don't know, like. I'm not saying, is it eczema? Is it psoriasis? You're like, this is just a weird dermatitis. Like, I. But I know now I've got. You know, I don't know. I've lost track of how many cytokines or molecules we can target. Right. So, like, could you theoretically use this beyond just the. Is it eczema? Is it Sarai.
- [20:05]
A
Oh, my God. He's about to replace all derm paths. All derm paths. We're just. We're gonna solubilize a little skin, filled it. Filled it into Dr. Damsky's.
- [20:14]
B
No, but it was like, this is what's going on. And this is like. And even more importantly, you know, we think this is so IL17 driven, or TNF Alpha driven. And here's probably where you'd want to start therapeutically.
- [20:30]
C
Yeah. I mean, even going back to our rich testing, I mean, we realized even since we put that paper together that a lot of people are ordering when they don't know what the diagnosis is. Maybe it's lichenoid and spongiotic. Maybe they're not, you know, sorry. As for, like, anoid, they want to know, is there IL17 there? Is there IL13 there? And almost at that point, as long as it's not MF or something, you know, the diagnosis becomes less important. What they can target therapeutically becomes more important.
- [20:53]
D
So, Bill, the. The paper that Dr. Ferris was talking about, these biopsies that were done, was this done on, like, before patients got any therapy with the clinician saying, I don't know what this is or what's this done on a biopsy of? Hey, I have them on this therapy. They don't really seem to be responding to what I have them on. I'm going to biopsy them and then get this rich testing. And does if. Does therapy? Like, how much does that affect the risk?
- [21:20]
C
Yeah, thanks. Yeah, it was a mixed bag. So we did this study on the first 120 or so cases that were received for testing. So as it was, everything it was a mix of patients that were new diagnosis. Mostly it was patients that had failed therapy. And some of them were on therapy at the time of the biopsy. Some of them were not on systemic therapy at the time of biopsy. So it really was a mixed bag. But we really wanted to just try to take a very focused look at how clinicians were using this to answer the more specific question. For sure, therapy can affect the profiles that we see. So as you know, TH2 inhibitors can skew to TH17, TH1, vice versa, TH17 havers consecutive TH2. So we definitely take that into account. But yeah, this was a very mixed bag. It was retrospective. It was the first 120 cases or so that we got and kind of took all comers.
- [22:12]
A
That is so freaking cool. When are you, are you getting close to publishing about this or like when's.
- [22:19]
C
Yeah, we've got a pre print up. You know, what's been difficult about this is we're very actively working on this. And so we've got one version of a pre print up and then all of a sudden we've got 100 new samples in. You know, our algorithms improve and our, you know, but, but it's submitted to a journal now and we're waiting to get some peer review back, but there, there's a preponent on met archive.
- [22:41]
A
Oh, I can't. I'll be emailing you to get the link for that. I'm so, I'm so excited right now.
- [22:47]
B
All right, Matt, why don't you do your paper?
- [22:49]
A
Yeah, yeah, let's, let's move on, Pat. Let's, let's talk about something a little more directly relevant to what people are going to see next week. So for our listeners, Dr. Davski is one of the leading national experts on gramulomatous diseases and just published a great piece on granuloma. Dr. Patton, let's go.
- [23:07]
D
All right, so yeah, my deep dive paper, it's available online June of 2026 from the JAD. Dr. Damski is a senior author. The title is Granuloma Annular An Updated Review of Epidemiology, Molecular Pathogenesis and Management by Faruhar et al. So after a quick little intro, paper gets into the epidemiology of GA more common in females. More often, 75% of the time it's localized GA. 25% of the time it's generalized medication induced GA can happen, but most often it's idiopathic disease. Associations are listed along with a recommendation for workup in Figure 1. Recommendations. Checking blood pressure TSH, HEMIN, A1C lipids, TSH, LFTs in everyone, as well as additional testing in patients with certain clinical features. So ra, anti, ccp, ANA in patients with things like joint pain. I typically, like, never work up GA patients. I mean, like, good, good review of systems, but outside of any review of system, like, I'm not doing anything. What do you like? Laura and Matt, what's your workup for GA patients?
- [24:16]
A
Nothing.
- [24:16]
B
Yeah, okay. Review systems. Yeah.
- [24:18]
A
I don't even know if I do review systems.
- [24:20]
B
Well, that is not surprising, being a bad doctor.
- [24:23]
D
Yeah.
- [24:23]
B
Yeah.
- [24:24]
D
It involves talking to the patients and car about them, so I can understand why you would want them to do that.
- [24:29]
A
I just look from the door.
- [24:30]
D
So clinical features are reviewed. Papules, annular plaques, patches. There's a perforating form I don't think I've ever seen. GA can be itchy or painful. In 25 of patients, that 25 was really high. I mean, for. For me, like, having symptoms with it is actually kind of rare. That kind of makes treatment a little bit tricky because patients are like, this looks terrible. And I'm like, well, is it. Does it hurt or is it itchy? And they're like, like, no. And it's like, maybe say that it hurts so we can get some things approved. 50% of cases of GA spontaneously remit within two years. Compared to adults, kids can be more likely to develop sub Q lesions. I did not know that before I read this paper. I don't see kids. Like Dr. Farah said, I don't see kids either. Histologically, palisaded and an interstitial form. Studies on pathophysiology support a T cell driven process mostly th1 interfere on TNF sort of picture that drives recruitment of monocytes, differentiation into macrophages. I mean, I still think we don't have a great idea regarding pathophysiology. You know, patients want to know what's going on here. And I like, say your. Your skin's inflamed and seems to be attacking. Maybe, you know, this stuff called collagen got a little bit damaged and. And the body thinks that that's something bad and so it's attacking it. That's kind of. That always seemed to satisfy them. So before we get into therapy, anything you would want to add to that?
- [25:58]
C
No, I just want to give a shout out to a couple colleagues, one whose name John Barbieri, and the other is Jeff Cohen, who's here at Yale, who have really done population EPI studies on GA for the first time. And have kind of clarified the incidence, prevalence in these comorbidities which influence the screening recommendations that we gave in the paper. And I get it about not screening patients, but metabolic comorbidities definitely seem to be important in these patients and pretty prevalent. I mean, the main thing that I like to point out is that there's often this question of, like, you know, does this patient with generalized GA have paraneoplastic ga? And you know, John Barbarian, like, what kind of workup do I need to do for this patient? Do I need to give it CT from head to toe? Do I need to do nothing?
- [26:44]
A
If you're about to tell us we need to start doing CTs on GA patients.
- [26:50]
C
Good.
- [26:51]
D
Yeah.
- [26:51]
C
Don't. Yeah, I mean, there's very good population level data now that solid malignancies are not increased in patients with ga, including at all ages, and that hematologic malignancies are increased as much as they are in patients with eczema and psoriasis, other chronic inflammatory disease.
- [27:07]
A
Anytime a patient ever says to me or anybody asks for a disease that's not. Has it, that doesn't. I was there was. Could I. Could this be cancer? I'm always like, well, you definitely could have cancer, but you are no more likely to have cancer than anybody else in the world. Like, is the. You know, I'm trying. Trying to be a little silly whenever I answer, but it's, you know that. Because when you. Well, there was a case report of someone who had bile duct malignancy and they'd be, yeah, that happened. You know, it's a coincidence. Yeah.
- [27:38]
D
All right, so paper gets into therapy. Nice flowchart. Figure 4, localized disease. Aisle steroids make the most sense to me. You could try topical, some topical non steroid meds. Algorithm splits at that point. So, yeah, I kind of like the. The algorithm because it was like, you know, we tried the steroids. Do you want to be more aggressive? Does it really not bother you? And so it kind of splits and they want to be more aggressive. TNF alpha inhibitors jacks less significant disease. Hydroxychloroquine is first line. Narrow band uvb make sure they don't have photo distributed disease. I totally did this once. Like, I was like, okay, ga and I, I really didn't appreciate that. It like stopped where her sleeves were and I threw her in the light box and it was like I doubled her bsa. I think oral row flumelast would be high on my treatment option list. I was wondering if you've watched our show, you've seen us talk about oral flumelast. Where do you think that would fall? Have you ever tried, even if not refumelast, have you ever been able to give eprima last any of these patients?
- [28:44]
C
Yeah, I mean, you know, without the, you know, like, real formal evidence. My personal experience is that oral refumilast, and yes, we do use it, probably is better than oral a premolast in terms of efficacy. And I.
- [28:58]
A
Definitely better. Definitely better in terms of pocketbook.
- [29:02]
C
True. For sure.
- [29:03]
A
Yeah.
- [29:03]
C
Yeah. I mean, I kind of think about them as similar to hydroxychloroquine. So it's not going to be a home run, probably for their ga, but it might, you know, in a baseball analogy, be a base hit or a double. Like it, it's. It's going to make it better, probably, but I haven't seen patients, like, totally clear on it.
- [29:20]
B
Are you able to get patients oral JAK inhibitors? I mean, it seems like the data would suggest that's probably our best option. I just have not been successful in getting them covered.
- [29:30]
C
Yeah, I mean, what I didn't realize early in my career was that TNF alpha inhibitors are really, really effective for ga. And so, you know, when I talk to residents, I often say, like, you see your patient with GA, they have 10, 20, 30% BSA. Like, imagine this is psoriasis. Is that a candidate for TNF alpha inhibitor? And usually the answer is yes. And so you should also think about that in ga, of course, you've got to get the TNF inhibitor. So I do usually use that, like, first line if we're going to go like the biologic advanced therapy route, especially with the metabolic comorbidities in the GA patients. But in my experience, probably 8 to 10 patients do really well. The TNF inhibitor, they're definitely a subset that don't respond, whereas JAK inhibitors pretty much always seem to work. And, you know, Cost Plus Drugs now offers generic topacity.
- [30:14]
A
Oh, my God. That's what I'm just gonna. I thought I was. I thought I might know before you, I was gonna be like, did you know tofacitinib is now 25 bucks a month?
- [30:22]
D
It's cheap.
- [30:23]
B
That's great. It's great.
- [30:26]
C
Yeah, it's huge.
- [30:27]
A
That's. That is. I mean, it's such a game changer. Like, it's going to be. Well, if there's one of these that affects your cardiovascular risk, this is it. But, like, you're miserable. I think it'll be okay.
- [30:38]
C
But that's.
- [30:38]
A
Yeah, it's like, oh, it's crazy. So it's been interesting. My experience with reflu molass for oral review as for GA is I've seen it work amazingly in the short term, but then it's not been rare that I've had. People like, kind of started to come back. I. I've heard that. I don't know. Have you guys heard that at all? You have from patients?
- [30:59]
B
I think I've had like an n of 1 on it, so I don't have a good feel.
- [31:04]
D
I have a couple people on it. And no, I don't have the. Like, it has lost effectiveness. I haven't seen that.
- [31:12]
A
Okay, fair. Yeah, it's right. It's one of those hard things. Like there's just not. If we could get every dermatologist in America together, we could probably get 100 cases of. Of generalized GA treated with refluvalast and find out. But yeah, the, the. So. Well, so bull. Patton, go. Go back to the flow diagram and like, in a, in a normal setting, what's for each of you guys, what is your first line? When there's like nothing special about the patient. Nothing. They. I've got ga. I hate this. I really want to buy, you know, I don't have diabetes. I don't have blah, blah, blah, like a normal healthy person. Patton, what's your first line?
- [31:53]
D
Hydroxy. Hydroxychloroquine. I. I would make it Roflumalast, but, like, reflumelast is just a longer visit. Right. I mean, you have to talk to them about cost plus and they have to sign up for it, whereas this other one is like hydroxychloroquine. It's a relatively safe medication. Talk to them about giving eye exams. I don't do labs for hydroxychloroquine. And you just send that to the pharmacy, like what the patients are normally used to. So that's the first one I use.
- [32:21]
A
I got to just say for our listeners, patents, most people do labs on hydroxychloroquine.
- [32:29]
B
I probably most people do labs, to be honest.
- [32:32]
A
Interesting.
- [32:32]
C
Okay.
- [32:33]
B
I kind of do you do labs with hydroxychloroquine?
- [32:38]
C
Probably after three to six months. And then if there, there are no changes, then you don't. Okay, I think it's enough for me.
- [32:45]
D
I may be a really terrible doctor with not ordering labs. I. I really need to think about lab this issue. All right, I'm gonna think about that tonight. I'll get back to you all.
- [32:56]
A
So I. I'll say I don't get a baseline eye exam. So I, I say let's wait and see if this is going to work. And then if it's, if you're going to be on it for a while, then we'll, we'll do an eye exam because it's, it can't hurt your eye. Even if you had an eye problem to begin with, like, it can't hurt your eyes. It's, it still takes forever to get deposited into your retina.
- [33:14]
D
Yeah. I tell them we'll get the eye exam after you've been on it for a little bit.
- [33:19]
A
Yeah. So, Bill, what about you? What's your, what's your first line?
- [33:25]
C
I mean, it depends what's going on with the patient. I mean, I, I, I think that I'm really biased by the referrals I get. I mean, a lot of patients come to see us in our GA clinic, and they've often tried and failed a lot of things like hydroxychloroquine. I mean, not to say hydroxychloroquine can't be great for a lot of patients, but a lot of patients I've seen have often failed it. Outside of that, you know, I feel like I can look a patient in the eye and say, like, I know a TNF alpha inhibitor is probably going to work for you. I know a JAK inhibitor is probably, almost definitely going to work to you, but you may or may not be a good candidate for it. And there's safety issues we need to talk about. And if you're not crazy about those options, which, you know, some patients aren't, like hydroxyl chloroquine, refumilast, supremolast. I mean, those are good starting points, and they, you know, they could work.
- [34:10]
A
Do you ever think that, like, the old school, like pentoxifyne niacinamide. Yeah. Like, do you think of that as basically placebo, or do you think they actually do work at times?
- [34:29]
C
I don't know. I mean, I've seen them, seen them work. I've seen dapsone work. I don't, I try to avoid prescribing doxycycline in general for acne patients, if I can avoid it. So it's just, I mean, a lot of the patients I see have generalized GA for 5 years, 10 years, 20 years. I mean, I don't know. I don't want to put them on doxycycline for the rest of their life, even if it does help them.
- [34:52]
A
So I've got a question that occurred to me. So I was talking to Ted Rosen recently and he was talking about how they'll do the scarification. Well, they'll take the little diabetes lancet and like jab it a lot. And I was thinking they've. I don't know if they, if you've ever seen these like on Amazon, they have these mic. They have these micro needle rollers that are like, you know, 1 millimeter deep and it's first wrinkles or hair loss or whatever. Just seems to. Do you, do you ever do like the cryo, the scarification, the. There was just that study out of China using heating pads. Do you ever try the physics? I mean, you're probably getting people, people who are like, you know, 60 of your body's covered in GA. But just. I gotta ask.
- [35:37]
C
Yeah, no, it's, it's a good question. I, I haven't. Yeah, I saw that heat therapy study. I think it's provocative.
- [35:46]
A
That's how I get, that's how I get described frequently.
- [35:50]
C
Cryotherapy is interesting. I mean, I just know from the literature, I haven't tried it myself, but I think from a scientific standpoint, they're very interesting. Okay. Yeah, but I haven't done it.
- [35:59]
A
All right, fair. And, and pat, I got to say before, I liked your description because it's exactly what I always say to people is, I think that your body thinks there's something damaged in your skin and it's trying to basically eat it and get rid of it for you. It's almost a foreign body reaction. You know, type idea is always my
- [36:22]
C
idea with a taste of autoimmunity. I mean, I think that gives us some insight that, you know, patients often have thyroiditis and, you know, the RA sle. There's, you know, other autoinflammatory autoimmune.
- [36:33]
A
I'm going to use that. A taste of autoimmunity. Oh, you've got a whiff, right? A whiff of autoimmunity. I like it.
- [36:41]
B
I have to say, I don't go to TNF inhibitors often, but this has made me think that should be more my first line. They're also much easier and much cheaper to get now with biosimilar adalimumab. So I think that's a great tip.
- [36:59]
C
Yeah.
- [37:00]
A
Are you able to get it? I mean. Right. And for our listeners, it's a, it's a kind of a known thing that if you get something covered off label a lot, you get better and better at it and it gets easier and easier. So Dr. Damsky, is probably about to say, yeah, we don't really have any problem getting it covered. Whereas if you go out and try and get it covered for the first time, you're going to be like, I had to write 19 letters and make nine phone calls and it, blah, blah, blah. But any pearls for getting it covered for off label use?
- [37:29]
C
No, I guess just being persistent. I mean, it's a frustration of practicing medicine. Yeah, I don't have any real pearls other than to cite the studies that are out there for TNF inhibitors. There was a really nice study from France that was published this year in the JAD. It's the biggest one we've had, which is 16 patients.
- [37:48]
B
Huge.
- [37:49]
C
We have 14 out of the 16 responded. And there's some other stuff in the literature. So cite that when it's appropriate. I'll have the patient write a letter of how GA is affecting their life. And, you know, I'll write a letter and.
- [37:59]
A
Okay.
- [38:00]
B
All right, that's great.
- [38:02]
A
Patton, you got anything left?
- [38:04]
D
No, that's the paper.
- [38:06]
A
Okay. All right, well, let's. Patton, do you have trivia for us this week?
- [38:09]
D
I do. It's really bad.
- [38:14]
A
You say that every week. Let's, let's see. We'll be the judge of it.
- [38:17]
B
Pulling up the trivia. I just want to ask. Ask you, Bill. I thought Matt was going to go into this, so I'm going to do it. You know, Castle Biosciences has this test now where they, you can send off scrapings and they do gene expression profiling of like, I don't know, 4,500 million and then tell you what drug your, your patient might respond to.
- [38:41]
C
Do you.
- [38:42]
B
Can you tell me, like, how. What do you think of that test? Are you guys using it? And how is, like, your testing different from that?
- [38:53]
C
Yeah, thanks for asking that. So I haven't ordered the Castle test. My impression from reading the literature and from talking to others that have ordered it is that, you know, most patients are a TH2 profile. And if you get a TH2 profile, patients do just about as well, whether they take a TH2 inhibitor or JAK inhibitor. So it doesn't really help too much there. If you get a JAK inhibitor profile, you get it, but it doesn't mean you can't respond to dupilumab. And I think most people would rather use or, you know, the other drugs in that class. I think most dermatologists probably would use that first line if they don't have a compelling reason to otherwise. So my personal opinion and the opinion you you know, others that I've spoken with is that it's just, it's not answering the critical question of like, I feel like we want to know who's going to do well with the TH2 inhibitor. It doesn't really. Doesn't really.
- [39:47]
A
And my take on it, they like to, to frame it as what identifies who's 2h2 dominant, who's not th2. It does not. Basically they fed in a whole bunch of genes and said what's turned on, what's turned off. And maybe that predicts who's going to respond to a doopie versus a jack versus who's maybe it respect. But it's not telling us who's th2 dominant and who's not th2 dominant. It's just this pattern of genes with it. Like it. It I. Tests like that I'm extremely skeptical of until they have a really like solid, you know, prospective big numbers of people. Like, maybe it works. But the, the prospective study they did was so small, it doesn't really prove to me at all that it works. And when it doesn't have a biological plausibility reason, like what you're doing, which cytokines are elevated. Okay, that should predict which cytokines we should block. Like it makes sense in the same way that a hemoglobin A1C makes sense. Like, well, if you're, if, if, if your hem, if your glucose is higher, your hemoglobin A1C is going to be higher and it's probably damaging your eyes and whatever. Like it makes sense. There's it. And yeah, that it's. It frustrates me how kind of it, how, how muddied that water gets of. Like, you know, it's fair enough the way I would put it.
- [41:12]
C
It's a lot of genes and, you know, a lot of immune programs. But yeah, I mean, I, I still like, if I had a biopsy in front of me and we look at the histologic features, we look, look at the cytokines. Like there's a lot of IL13, maybe there's a little interfering gamma. I mean, still, at the end of the day, I can't say absolutely this patient will respond to dupilumab or they absolutely won't respond to dupility map. But a lot of times clinicians, like, say you have a patient with eczema, they treat it to pilumab, they fail it, they do a biopsy. Like, sometimes it's just helpful to know like, yes, this is eczema. No, it's not MF. No, it's not psoriasis. Like we have some IL13 expression. We've got maybe a lot of interferon gamma expression. Like this patient has eczema, but maybe we see why they didn't respond to pilumab and they take that next step. But I think like on a one off patient before treatment, with the risk testing, it's hard to. To know. But we're hoping that this other approach that we're developing will be able to answer that question. Yeah.
- [42:05]
B
So you'll look at all the big cytokines with your protein assay?
- [42:08]
C
Yeah.
- [42:09]
B
Okay. Yeah, very cool. And do you try to target like here are the proteins to which we actually have, you know, targeted therapies. Let's look at those. And then hopefully, then you could prospectively test and say, yes, you Got lots of IL13, I think this is the drug, or you got lots of interferon. Therefore, I think this is going to be, you know, driven. Right.
- [42:32]
C
Yeah. Working on setting of external validation. So we'd like to get this in the hands of others who can test it in their hands without our influence and see how like it's working for them. So we're going to use our models to, to prospectively evaluate this or validate it hopefully at other institutions.
- [42:46]
B
Great. All right. Sorry, I didn't mean to derail the trivia.
- [42:50]
A
No, no, I dropped the ball.
- [42:51]
D
I forgot we wanted to talk about that, so we did. Reviewing the show notes. We don't have show notes. All right, all right, let's go. This is granuloma eponyms. Number one.
- [43:07]
A
Okay, okay.
- [43:08]
D
This Australian pathologist described GA like lesions that occurred primarily in sun exposed skin.
- [43:16]
A
O'. Brien.
- [43:16]
D
Yeah. O' Brien's actinic granuloma.
- [43:20]
B
Wow.
- [43:21]
D
1975. Published in Archives. All right. In 1883, this Italian dermatologist described a deep chronic infection of the hair follicles.
- [43:32]
B
Mayaki.
- [43:33]
D
Mayaki's granuloma. Dominico was his name. Good Italian.
- [43:38]
B
Okay, we didn't give you all the the lowdown. Now we've each scored a point on you, but if, when he finishes now,
- [43:46]
A
we'll tell you the rules.
- [43:46]
B
Just scream out the answer.
- [43:49]
D
Oh, wait. Let's start over. Okay, number one. All right, number three. In 1947, this Swiss dermatologist described the well defined nodular aggregates of histiocytes arranged around a slit like space seen in erythe. In a doome.
- [44:06]
C
Me sure.
- [44:06]
D
Me.
- [44:08]
B
Yeah.
- [44:09]
D
See, it's a three way tie.
- [44:10]
C
Thank God we didn't.
- [44:11]
B
A three way.
- [44:11]
A
Thank God we didn't tell him the rules at the beginning.
- [44:14]
B
I know we would have.
- [44:17]
D
All right. Three way tie. Those are rare, but it happens.
- [44:22]
A
Okay. I'm glad I knew.
- [44:23]
D
O'.
- [44:24]
A
Brien. All right. So, Bill, thank you for coming on the show. This was, this was a phenomenally good discussion. And I am, like, really excited to, to see where what you guys are working on goes. I think it's, it just sounds incredible. This is great. Just a fun discussion. But so, you know, I want to thank all of our listeners for tuning in. We hope you laughed once or twice. We hope you learned a few things, but mostly, we hope you're planning to join us next week. Until then, I'm Matt Zyrus.
- [44:54]
D
I'm Tim Patton.
- [44:55]
B
And I'm Laura Faris. And we are Derms on drug.