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- [00:03]
A
Welcome to season three of Derms on Drugs, a video podcast brought to you by Scholars of Medicine. The best educational platform in dermatology and provided at no cost to medical providers. Terms on drugs is where cutting edge term meets hit or miss comedy. I'm Dr. Matt Cyrus from Docs Dermatology and each week I'm joined by residency buddies Dr. Laura Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh. And we use our 60 years a combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of derm and you'll have some fun listening. New episodes drop every Friday on Scholars in Medicine, Apple Podcast, Spotify and other major podcast platforms that I highly recommend that you download the Scholars in Medicine app to access the full podcast video archive. Explore the best educational derm content out there. Not, you know, this pharma driven. What's the low there a new approach to no like actual coverage of useful topics right in all of dermatology supported by an amazing AI clinical consultant called Ask Simon. So this week we've got another one of our patented six pack episodes and we are going to go ahead and kick it off with Dr. Faris. What do you got?
- [01:14]
B
Okay, I have a paper that was published in JAD and this is the 4487 gene expression profile test guide. Systemic therapy selection to improve outcomes for patients with atopic dermatitis. Results from a prospective trial, Jonathan Silverberg et al.
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A
Okay, 487.
- [01:36]
B
That's 487 genes. I didn't even know that there were 487.
- [01:41]
C
I thought we only had like 250 genes total.
- [01:44]
A
It's. I know, kind of like the Baskin Robbins of gene expression profiling.
- [01:48]
B
Now that was the. That's the other one flavor. Yeah, this is like, I don't even know what has 487. It's like a video game or.
- [01:57]
A
All right, okay, let's go.
- [01:59]
B
So what is this? So basically what they wanted to do was just answer the question, you know, people with atopic dermatitis. Can we predict who is going to do better on a biologic, primarily DUPY or versus like who's going to do better on a JAK inhibitor. So I think most people's algorithm is start with an antibody, then if that doesn't work, go to a JAK inhibitor. But you know, we know there's probably TH2 driven atopic derm and non TH2 driven. And so can you decide this, you know, a priori, can you decide this upfront and then put them on the right drug? So, you know, what would that do? It would let you, you know, pick the right drug, let patients get better faster and you know, also kind of give you a little bit more rationale than just, you know, try fail, try fail. So what did they do? They, and I actually participated in this trial when I was at the University of Pittsburgh. So you have a patient, they've got ad, you're about to start them on a new drug, you as the invest, you as the treating physician picked like, oh, I'm going to start you on dupy or oh, I'm going to start you on, you know, this Jack inhibitor. And so they enrolled 11, 81 patients. And this is, so this is just the AD paper. They, they could be, they could have AD or psoriasis. So hopefully we'll see a psoriasis paper out of this too. And that at each visit they took these like, basically took a curette, scraped this lesional and non lesional skin into like some, something called RNA later, and then they did targeted RNA sequencing. And, and then they, so they, they came up with, they basically divided this into like a development set and a test set. And, and then they validated it on, you know, patients who were not in the development set. And then the measures that they looked at were things like easy, BSA, IgA, the promise itch score, flares and DLQI. Okay, so they used 321 patients who had been treated for AD or psoriasis to train. It interrogated expression of 487 genes across, you know, 12 inflammatory pathways. And they came up with like a TH2 profile or a JAK inhibitor responder profile. And then they, they used 66 AD just for the AD part, 66 AD patients who had at least a 50% improvement in easy in a given therapy class. And so they locked in that algorithm and then they validated in 110 AD patients age 12 and up, and they, they used 25. So using just like standard practice, basically, if they looked at sort of everybody like what was the outcome of these people who happened to get, you know, enrolled, 25.2% of them achieved an easy 90 by three months. So that's pretty much in line with what we would see in trials and in real life. So in the validation cohort they found that about 30% of AD patients had a JAK inhibitor responder profile, about 70% had a TH2 profile. So if they looked at the JAK inhibitor profile. The people who were like, predicted to be JAK Inhibitor responders, about 45% of them achieved an easy 90 by three months, compared to only about 8% if they were treated with a TH2 targeted biologic. So basically what they found is if you are a JAK responder, you're going to do way better on a JAK inhibitor. So if you're a jack responder and you get dupy, only about 8% of those patients are going to have an easy 90. Whereas if you're a JAK responder and you get a jak inhibitor, like 45.5% of those are going to achieve an easy 90. Now on. And they hit that endpoint faster, 3.8 times faster on a JAK inhibitor. And they also did better on stringent endpoints. So 36.4 had an IGA of.0, 0% BSA versus none of the TH2. Those people who are put on a TH2 targeted therapy also like, more likely to have no itch, et cetera, et cetera. And the other notable thing is that everyone in that JAK inhibitor responder group who hit easy 90 by 3 months did so on the lowest dose of JAK inhibitor, so they didn't have to go up. How about the. Those most of the people did have a TH2 profile. And, and for them, they basically had no statistically significant difference in easy 90 rates or speed of response or 0%. So if you're a TH2, you, you basically are going to probably do about equally well on an antibody or a JAK inhibitor. If you're a JAK responder, you are going to do way better on a JAK inhibitor than you are on an antibody. I thought that was interesting.
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A
My biggest criticism of this, and maybe it's in there, and I just didn't see it. There are some people in the atopic dermatitis world who really like to make a big deal out of the easy 90 response. That, like, that should be our endpoint. We shouldn't care about easy 75. And I think those people are dumb because patient after patient after patient.
- [07:40]
B
But how do you really feel patient
- [07:43]
A
after pay, having done clinical trials and having a really good sense of what Easy75 looks like compared to Easy90. There's not a single Easy75 patient I've ever had who has wanted to switch drugs. Every single one of them is happy with the response. Like, would they rather be easy 90? Sure. But if they'd rather be easy 100 and they'd rather be easy 120. Like, like, whatever. It's easy 75 is the endpoint that matters. Like, just for clinical care, E75 is what matters. And I didn't, I don't think they reported easy 75 in here, but overall, I thought the results were kind of expected. So there was a study a couple of years ago, I think Danby from Yale did it, where they did biopsies and they showed that you could predict doopy response based on essentially how much IL13 was in the biopsy, which was like, it was an interesting thing to me that, I mean, I know it's so, it's Castle. They do gene expression profiling. If you have a hammer, everything's a nail.
- [08:46]
B
It, Although I will say that it is just like scraping the skin into. It's better than. And it's a quicker test. Like, I, I say that that beats having to do a skin biopsy and quantifying IL13.
- [08:58]
A
Right, I agree with that. But you should be able to do skin tape stripping for cytokine profiling.
- [09:04]
B
Yeah, but what's cheaper than, than a curette, right? I, I like the simplicity of this. There's no fancy tape.
- [09:12]
A
It's not the curette that you could probably do the curetting as well for the cytokine profiling. The cost is in the, the gene.
- [09:20]
B
You're saying, you're not saying it's the mechanism, you're saying it's, look at IL13. Don't look at 487genes.
- [09:25]
A
Yes. Just look at like, you know, whatever.
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B
It's cheap.
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A
But okay, yes, that's the thing. PCR is cheap and it's what Castle is good at already. So I get it and it, but it, it makes sense. Like, it's a good, like, you know, I, I, I could see using it.
- [09:42]
B
So I'll tell you where I think that this could be helpful is, you know, well, one, if I could use it prospectively and say, I mean, 2/3 of the time it's going to say just start with an antibody. Right. But let's say my patients who are on DUPY and they're not doing great now, it's like, do you put them. It used to be like, okay, we're going to go to a JACK inhibitor. But, you know, now I have the option of like, do I want to put them on lebracizumab? Do I want to put them on nemalizumab? If I had this and it said like, they're a JACK inhibitor responder, I'd feel pretty good about just Switching them, I wouldn't feel. Or, you know, like, oh, I got to go to Trello now. Or, you know, I wouldn't feel like I needed to go through another antibody or two. I would feel good about putting them on a JAK inhibitor. I also like the fact that it also predicts that they're going to do fine on the low, the lower dose of the JAK inhibitor, which has a better safety profile.
- [10:36]
A
Once again, Farris, you're being the smart one. That actually makes tons of sense to me as a use at for dupy. Inadequate responders. If they're an IL13, they're not a Jack responder profile, but they didn't respond to dupy. That probably means they're more likely to respond to, you know, Lebry, Trelo, Nemo wildcard in this whole thing. Don't know, but that's really. That's interesting. I hadn't thought of it that way at all.
- [11:08]
B
So, yeah, should be interesting. I agree. I do not see that easy 75 is in there. Even trying to look at, like, supplemental data. So. Yes, we don't know that.
- [11:21]
C
But, yeah, I, I thought the same thing. Like, if, if you're a TH2 responder, like, if you have that profile, then theoretically it'd be like, doopy is totally designed for you. And 25% of patients, like, if you didn't know anything about easy 90, whatever you would say, geez, even if you're made to get dupy, only a quarter of patients really respond. Like, that is not true. Right? I mean, if you respond as I feel, great. This drug's great. You know, I don't know what that, what that objective measure is. Maybe it's the easy 75.
- [11:59]
A
It's roughly easy 75. It's. And it's actually even a little below easy 75, because when you look at drug survival, about 10% of people stop DUPY because it didn't work well enough. 90% of them stay on it long term.
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C
And the, the doopie failures, it's tricky, right? I mean, we. We had that atopic derm, and, like, what matters to patients, right? It was safety. That was the biggest thing. More efficacy, too. But yeah, that was the thing that patients. So if you say, look at. You're a. You're a Jackie responder, like, there's a good high likelihood you're going to respond to jack. They may say, well, side effect profile of that versus Libry, you know, because now you're on, like, the second level. And they may say, yeah, but it's not like there's no way lebry will work. Right. That's not. We don't have the data to say that to them. So it's, it's, it's still going to be more of a safety thing. Even if, you know, if they're a jack responder or a TH2. So it's a TR, like incorporating this. Like, do I see me doing it tomorrow? Like, if I had the test, would I use it for a DUPY failure? I don't know. I think I'd have that conversation first. And if they said, I'm, I'm done with my eczema, what do you think is going to be the most effective drug? It's going to be Jackie. I don't need the test to put them on that. And if they say those jacks that sound scary, then you're going to go on Libry. Even if the test said you're a Jackie? I don't know.
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A
You know, it'd be much better if they came out with a487,488 gene expression profile that predicted the risk of a heart attack or a blood clot on a Jack. Then you, then you could be like, you know, they could just include that in the test. They don't even need to do anything. Just put it in the test and when they give the response back. So you're, you're no elevated increased risk of having a heart attack because of the JAK inhibitor. Because we know that's just true for everybody.
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C
There you go.
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A
So they could just add it in. That works. This give.
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B
It's their baseline risk is what matters. Right? I. I don't know. I think that the reassurance of the lower dose is, is nice. I think that that's helpful. So I don't know. I thought this was good. I mean, you know, people didn't get randomized the treatments, but it's. I thought it was pretty compelling.
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A
It was, yeah. Agree. All right, Patton, what do you got?
- [14:27]
C
My first six pack was published online January 2026 Jamaderm. It's titled Methotrexate and mycophenolate. Mofatil and Clinical Response in Juvenile Localized Scleroderma by Derosas et al. There's a retrospective study of 114 patients with juvenile linear scleroderma. Treatment of JLS has classically been prednisone and methotrexate. It's a protocol published here at the University of Pittsburgh 2012 by the Senior author on the paper that I'm doing. Dr. Katherine Torick. Do you know what. Katherine Torick. You know what name she goes by?
- [15:02]
B
Cassie.
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C
Cassie. That's a unique name for Catherine. I would have never guessed that.
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B
Yeah, it's a good one. I like it.
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C
Yep. Retrospective Study performed at UPMC Children's 2010-2023. 114 kids with JLS. 68 patients on methotrexate, 28 on mycophenolate, 18 on both. Baseline characteristics are in Table 1. Most baseline characteristics were similar, except the mycophenolate group had a longer disease duration and a higher PGAD score. So when they're doing scleroderma, they do PGaA, which is activity, erythema, induration. PGAD is damage, atrophy, hyperpigmentation, things like that. So at baseline, these were not the same patients. This is a retrospective study. Mycophenolate, longer disease duration, higher PGAD scores. Table 2 shows treatment response as measured by the modified Localized Scleroderma Skin Severity Index. And the response between methotrexate and mycophenolate was the same. No differences in flares of disease between the two groups. Table 3 examines adverse effects. And methotrexate had way more of those, like 60% versus like 15 or something with mycophenol. So nausea, fatigue, anxiety, anticipatory vomiting. That is a. That is a hell of a side effect. They vomit at the idea that they're going to get their methotrexate because it causes so much nausea.
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A
Did you used to have that problem with girls in high school?
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C
Yeah, this is on my, like, Tinder profile.
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B
May cause anticipatory laughing.
- [16:39]
C
Yeah, and it's a big turn off. And, you know, my dating life suffered because of it. Looking at the bar graphs in Figure 2, it actually looks like methotrexate's better. Like a higher proportion of improved, lower proportion of worsen. But I guess there were like more mf, mm mycophenolate patients that didn't follow up. So those numbers are somewhat distorted. Plus, the mycophenolate had longer disease duration, higher PGAD scores. So if you look at those bar graphs and be like, okay, they say in Table 1, they say they're the same, but these bar graphs, it really does look like methotrexate's better. A lot of that is just larger numbers of patients. And so the proportions are affected by that and also worse follow up in the mycophenolate. So that's it. I mean, you know, linear scleroderma, I think that is In a fair number of dermatologists, wheelhouse, you know, rheumatologists, like, they'll look at linear scleroderma and say, look, you don't have systemic sclerosis. This is a skin issue. Go see derm. I think standard is that prednisone methotrexate sort of protocol that Dr. Torick published in 2012. And, and I mean, that's a really nice paper. You talk about, like dupixent showing you how to taper prednisone in. In BP patients. That paper that Dr. Torick published, it's like, here's where you start. Here's when you start to taper, here's your starting dose, here's how long you continue the methotrexate. It's this two year protocol and it lays it out. I mean, that to me is standard of care. I thought it was interesting that even Dr. Torick at this point is saying mycophenolate is not a bad option. And with just the high rate of adverse effects that was in the methotrexate group, maybe we start there. Mycophenolate is like systemic sclerosis, which used to be methotrexate. Methotrexate. More and more rheumatologists are actually using mycophenolate for systemic sclerosis type, you know, like interstitial lung disease and things like that. They kind of like mycophenolate better than methotrexate. And I wonder if the same thing's going to happen in linear scleroderma. What do you guys think?
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B
Yeah, potentially. I mean, I thought that was interesting. I guess. One, I don't think of methotrexate as being that hard to tolerate.
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C
I was surprised at those numbers. Yeah, kids.
- [19:04]
B
Kids. Yeah, they're so persnickety sometimes.
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A
They were probably just. You were just faking it to get some extra ice cream and screen time.
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C
But then fake it with my cafe.
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B
Yeah.
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A
Shut up.
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B
He's just being mean.
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C
Shut up, shut up, he said. See, again the discourse.
- [19:24]
A
That's how you know when somebody's really winning the argument. When it's.
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C
Shut up, shut up, you're ugly.
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A
All right, let's move.
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C
You make me anticipate pory vomit.
- [19:35]
A
Let's move on to mine. All right, first one that I've got here. This was just a cool article, like, out of the blue. Wasn't expecting this. So, IL31 blockade elevates TARC by lifting lamp 3 plus CD1C positive mature dendritic cells. From CGRP, calcium neuroimmune suppression in atopic dermatitis. This was in the Journal of Allergy and Clinical Immunology and here is the summary. So super cool. So they looked at four patients who had cutaneous adverse events from nemalizumab. So right. It's a common thing that people talk about like oh Nemo, like made my patients itch like go away immediately. But their skin didn't get better or maybe their skin even got worse. And it's always been like why has that happened? Like is it just that it only works on the itch and it doesn't work on the, the inflammatory components early on? Well here's what they showed. That in your skin your itch neurons release cgrp, calcitonin gene related peptide. And the CGRP keeps your dendritic cells in a naive state. And whenever you turn off the itch neurons, they stop releasing the cjrp, your dendritic cells. And it's one particular type of dendritic cells. But who cares? Your dendritic cells now mature and start to make more tarc. And TARK is a cytokine that is thought to be one of the fundamental cytokines that is like upstream driving atopic dermatitis. And so it, it, if the, this could really explain it. Well because the expectation would be that the IL31, if the, the lack of itch, if it's not working well on the itch, then it's not going to cause the tark to go up. And so it's, it may actually be that the better it works on the itch, the more it makes TARC go up. And so the more likely you are to have like this skin flare early on that then is going to go away with time. So it was just mechanistically interesting that maybe there is a reason that we kind of see that with Nemo. And they said that they in their data that they'd seen it in 40% of patients. But the main takeaway is if once they're itches better, if you give them enough time, the TARK comes back down and then they do okay is at least the expectation. But just.
- [22:09]
B
So can I ask you, what do you give? Like, so I did some like the NEMO study. I probably had like one or two people in it. I didn't have like this wealth of experience watching it, but I do kind of remember like my one patient who ultimately did well, like not doing super well initially and then getting better later. Is that what you saw?
- [22:28]
A
Absolutely. I saw. Yes. But their itch was okay. Like, they were not. You looked at them and were like, you're not getting better. And they were like, oh, my God, I'm so happy. I'm so not itchy. If you give. If you just let it go, they will. Eventually their rash gets better. I had, like 30 people in that trial, and it, like, if you give them the time, it gets better.
- [22:49]
B
And we couldn't use topical steroids, if I recall, in the trial. But, like, what do you do in the real world when you're using Nemo and they start to get that rash? Are you, like, just hang in there. Here's some triumphant alone. Treat your rash like, this isn't a forever thing, or what do you say?
- [23:05]
A
Yes, that. Here's some. Here's some topical. Give us some time. If they're, like, really bothered by the way that it looks, I'll talk to them about a shot of kenalog. You know, talking about, oh, there's steroid side effects and the blah, blah, blah. It would be reasonable to give them some cyclosporine or, you know, some JAK inhibitor. But I usually end up just doing a shot of kenalog if they really want something. But the majority of the time I just give them tack and they're not that bothered by it because they're just so happy. They're not itchy anymore.
- [23:36]
B
Okay, that's great.
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A
Helpful study number two. This actually was not a study. It was more of a review. But I was so excited when it came out. So Decision making Factors for Systemic Therapies in Atopic Dermatitis. A clinical review. So this was something. And I was like, they did a pretty good job in this article. So I recently put together a lecture that was kind of exactly this. Like, how do you pick which drug? And I made a little scoring sheet that basically goes through the different factors. And it's a scoring system. Like, you get, this drug gets plus one for this, this drug gets minus two for that. And you just go through and ask these questions, and it tells you what's the best drug to put them on and the questions that you ask. And their study confirmed all of it. Number one, do they have atopic comorbidities? They do. Doopie gets a point. Do they have a history of staph infections? If yes, Dupy gets a point. And Adbree Ebglis get a point. Sebanco and Rimbo get a minus one. Warts from Aluskum. Doopie gets a plus one. Sabanco and Rimbo get a minus one. But. And you just, you go through a bunch of those. The other things that you ask, do they have cancer or a history of chronic infection? Do they have a history of arthritis, psoriasis, seb derm, or is it a psoriasiform rash? Do they have significant facial involvement? Do they have a history of ocular disease? Are they highly needle phobic? Is their itch out of proportion to their rash? Do they have any other autoimmune diseases? Do they have a history of HSV or vzv? Do they have a history of blood clots or extremely high cardiovascular risk? And are they a female of childbearing potential? And so those are all the factors that do go into this that I've always thought about. And, but you know, the question is, well, how do you weigh all of that? So that's why I put together this little scoring sheet. I totally made up the scores. So like the. Does this get. You get a plus one, a minus one, you get a plus five, a minus five, like, whatever. But just based on all of my clinical experience, we will have that live on the SIM somewhere. Scholars in medicine. So if anybody wants that, because it is like pretty darn useful to just go through with a patient like, check, check, check, check, check. And then here's a score. Like, each drug gets a score. And you can be like, okay, you scored best on like number four. So it can be helpful if you are somebody who struggles with that.
- [26:09]
B
I think that could be really great for patients just because, like, you know, like you said that like the. We try to like, give them all this information and they're like, I don't know, tell me what to do.
- [26:21]
A
Right?
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B
And like, you try to simplify it. And like, everybody loves those online quizzes, right? Like, answer these questions and we'll tell you what your best. You know what I mean? Like, what you should make for dinner tonight.
- [26:34]
A
What kind of car should you drive? Will you get anticipatory vomiting?
- [26:39]
B
Exactly. All those kinds of things. And so I like, I think, and to some degree, if it were an app, I think patients would like, trust it. Be like this says there's a validated algorithm. And it says, the best drug for me is blank.
- [26:55]
A
Yes. Well, it's only validated by Mad Zyrus, but it's okay.
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C
That's all I need.
- [27:01]
B
Well, and that paper sort of.
- [27:02]
A
But the paper doesn't give you a scoring system. It just is like, here are the factors. But it didn't feel like, here's how to use them. So that's the.
- [27:11]
B
That's okay. You're very compelling. Even without data, I think you can make it work.
- [27:15]
A
Wow, thanks, Ferris. That might be one of the nicest things you've ever said to me.
- [27:20]
B
It might be. It probably will still remain that way for a long time.
- [27:25]
A
All right, next study. Ferris, what do you got? I'm excited about this one. This one seemed really cool.
- [27:31]
B
Okay, this is a single arm phase two study of tvec because I can't say the whole name. Right. The tal. Yes, TVEC in patients with lower risk invasive cutaneous squamous carcinoma.
- [27:44]
A
Explain briefly what it is. Yes, sir.
- [27:47]
B
Okay, what is TVEC? It is a modified herpes HSV1 virus that expresses GM CSF and is sort of modified so that doesn't have uncontrolled replication. So TVEC is currently indicated, FDA approved for the intralesional treatment of melanoma mets. So you usually, like, when you're using tvec, you're using it in advanced like cutaneous or deeper mets of, of melanoma. So this is saying like, what if we just use this in sort of a really low risk, lower risk disease, like low risk cutaneous scc. Okay.
- [28:25]
A
Yep.
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B
Sing. Single arm, single site, phase two study at the University of Arizona Cancer Center.
- [28:32]
A
Wait, wait, I know, I know you. I'm sorry for interrupting.
- [28:35]
B
No, I love it when you please interrupt me.
- [28:38]
A
Explain a little bit. So it's, it's just a modified. It's just like a weaker herpes virus. Like what is it?
- [28:45]
B
It's modified. There's one of the genes and I can't remember off the top of my head what it is. So it's like, it's not like, you know, if you had never had HSV1 and I gave and I like injected a bunch of it into your skin. Like you get kind of a rip roaring HSB1. It could like, you know, spread, you know, it is modified to have like limit, like so that it really should only be replicating within tumor cells.
- [29:11]
A
Ah, so it's, it's, it Herpes. Okay, got it.
- [29:16]
B
But in theory you could still like, let's say it went out of control and I've never heard or seen this happening, but you could still treat it with like valley cyclovir if you needed to.
- [29:25]
A
Okay.
- [29:28]
B
Okay. Eligible tumors, 0.5 to 5 centimeters. So up to decent sized tumors, well to moderately differentiated. They could not have a thickness of greater than 2 millimeters. They could not have high risk things like perineural or vascular involvement. And interestingly, they did not treat ones that were on the face, neck, hands, nails or ankles. And each patient could have up to five confirmed invasive SCCs that could be treated as target lesions, which they call TLIs, which are targeted target lesions injected. And then they could also have untreated non target lesions so nearby squames that they just kind of follow for like abscopal effect. So small study 11 patients, 24 tumors. About 83% of those were, well, most of these were T1s and a few T2As. So the lesions averaged around 13 millimeters. So you know, they could be up to 5 centimeters, but most were 1.3 centimeters. They were injected every two weeks starting at, you know, the low dose and then going up to the high dose of TVEC and up to four injections per lesion. And they use like standard melanoma dosing. And they followed patients with in person visits up to 28 weeks after the last injection and then out to two years. They, they just did like record review because one of the things they didn't just look at like did these tumors clear? One of the end points they looked at was how about your like developing new tumors as well. So the Overall response rate 100% by patient and tumor. So every injected lesion responded. So complete response in 90.9% of patients and 95.8% of tumors. So 23 of 24 lesions and so one tumor was a partial response and stable median timed response, 35 days. Mostly they responded in the first one to two months. Median duration response was 212 days at the patient level and 209 at the lesion level with no recurrences. So you're like, oh, it only lasted 212 days. No, this was basically like, this was based on the study length. Like I actually think you would more report this as like median duration of response was not reached. Not that, you know, it was 212 days. That that time was not when half of the tumors came back. That was kind of based on when the study ended. So a little bit of a, a nuanced thing, but I think important safety wise, nobody dropped out from adverse events. They, you know, TVEC does give you some people's flu, like, you know, fatigue type syndrome. And they did see that most people's like grade 12 handled with NSAIDs. And so here's where it gets, I think kind of interesting. At two years after treatment, the number of new invasive cutaneous claims per patient was, was significantly lower than both the one and two years before. The tvec. So you know, if you looked at sort of, if you look at the sum of the two years, two years and one year before tvec. The. If you look at all at squams, all squams plus or if you look at just invasive squams, you would. They had 9.7 in the year in the two years before and then in the one in the two years after they had 5.5. So I thought. And that P value was significant. So I thought that was interesting. In the non injected lesions they had two. They had two lesions that had complete responses. So abscopal effect. So hypothesis generating. Interesting. Um, but you know this could be really helpful. And where could it be really helpful? Like transplant patients. Right?
- [33:51]
A
What did you call that? The ad scopal response.
- [33:53]
B
Abscopal effects response which is where you treat one tumor but you get a response in your non target tumor. And the idea is that you're generating an immune response and that is what is curing tumor. The, the uninjected tumor.
- [34:09]
A
So they, how many untreated? Two. You said two of them went away. How many were there altogether? Was there like 200 of them or were there like 5 or 10 or.
- [34:19]
B
It was few. I'll, I'll find you the exact number in just a moment.
- [34:25]
C
Abscopal. Abscopal effect is described in radiation. Right. Radiation oncology is probably where cuz you radiate the tumor and you get lysis of tumor antigens and that has an effect on tumors that aren't irradiated.
- [34:42]
A
Never heard of such a thing. I've heard like. I. It's so it's kind of like whenever you inject the mother wart with Candida and all of their warts go away.
- [34:50]
B
Yes, it is exactly the same thing.
- [34:53]
A
Okay, Abscopal effect.
- [34:55]
B
I'm gonna start using abscopal effect.
- [34:58]
A
I'm gonna start using that all over the place. There's a. Lots of, lots of places I can use that.
- [35:04]
B
Okay, so I think this is interesting. I think it is, you know, probably like there's a lot of interest now in intralesional therapy for tumors. So of course we know 5 Fu methotrexate cutaneous squamous cells. You know we, we've got decent data and I think a lot of people do that. The idea of like doing something that's more like immunotherapy intral is interesting. Particularly if you reduce the number of future tumors or you treat, treat more of them. There is an ongoing study that we are doing of intralesional simiflumab. The PD1 inhibitor for cutaneous squamous cells. I think that's going to be interesting. There is a Verica has an intral oncolytic peptide that they are using to study in basal cell carcinoma. The idea being that it also has like some immune immunostimulatory, you know, properties. So I think it's going to be interesting to see where this all leads. You know, is it as cheap as like ED&C or excision? Probably not, but you know, like, TVEC can be helpful in melanoma patients who really, like, are out of options. And you know, I think that this could be like, what do you do with your, you know, your transplant patients, for example? So this can be immunostimulatory, but it's not like a PD1 inhibitor where you're like, well, what if there's systemic impact and then they reject their organ? So I, I love the idea of this. I think it'll be interesting to see where this all leads.
- [36:39]
A
I think that the long term data were. Because those graphs were pretty impressive of like the coming down the number of lesions out to two years. Like, that was cool. Like. Yeah, that's cool. I mean, this is it just one injection into the tumor once or do you do it like once a month?
- [36:58]
B
No, they did several. They did them like, you know, I think up to like four injections per, per tumor.
- [37:05]
A
Okay, okay. It's good stuff. All right.
- [37:10]
C
It's technically difficult, right? Don't you need like a super duper freezer and like, you know, incorporating this into everyday practice is not straightforward, is it? I mean.
- [37:26]
B
No, it's not. So. So yes, like, you have to, you know, you have to have like certification to be able to do this. You have to be, you know, trained to handle this. This is not going to be like throw a vial in your fridge next to your candida and start doing this. Right. It's, it's going to be harder than, you know, intralesional methotrexate or 5fu. But if you're a big center where, you know, you're already doing tac, let's say for melanoma and there are derms that do that, then I think that this is going to be, I think it's going to be interesting. Right?
- [38:03]
C
Another indication.
- [38:04]
B
Yeah.
- [38:04]
A
Yeah.
- [38:06]
C
Cool.
- [38:08]
A
I could really see it also being useful. You know, I think people struggle with the patients who have like getting eight swings a year, like, and there's their surgical fatigue and they don't want to, you know, if you could Just treat. Hey, this year we're going to try doing this and maybe you'll stop getting squ like that. Be super useful in those people.
- [38:32]
B
Yeah. And there were only two target not injected lesions.
- [38:38]
A
And they both got better.
- [38:39]
B
And they both got better.
- [38:41]
A
Wow.
- [38:41]
B
Okay, so, yeah, I thought it was that, but I wanted to make sure, so. Yeah. Interesting.
- [38:48]
A
Let's go. Patton, what do you got?
- [38:50]
C
Second six pack from the March 2026 edition of oral Diseases titled Diagnostic Delay and Desquamative Gingivitis. An observational cohort study by Kajulia et al. There was also an author with the name Dentico, which. I mean, is that a great name for a dentist or what? That's like a dermatologist named Skinner. Do you know that has a name, that there's a term where your name matches, like, what you do for a living? You guys know what that word is?
- [39:21]
B
No, but I know you're gonna tell us.
- [39:23]
C
An atronym. That's an actual real world real word, I should say. All right, some interesting points. Like, it's an apt name for you. Actronym.
- [39:37]
B
Wow. Okay.
- [39:38]
C
Abscopal aptronym. Next week we move on to bees. All right, some interesting points in the introduction, 85% of dentists report difficulties in diagnosing discriminative gingivitis. We're just going to call that DG93. This is crazy. 93% neither perform biopsies nor consult colleagues. I mean, that's hilarious. Like, not for the patients, but you can't make diagnosis of, like, LPPV or MMP without biopsy. But these dentists. This was in a previous study. That was the survey. They said we're like, yeah, we don't biopsy or refer. We just kind of. I don't know what they do.
- [40:16]
B
What do you say? Like, just deal with it. I don't know what it is. I'm not gonna find out.
- [40:20]
C
There's no come back for a cleaning.
- [40:21]
B
I could help you.
- [40:23]
C
If you want a fluoride treatment, use
- [40:25]
B
your fluoride and I'll see you in six months.
- [40:27]
C
Anyhow, all of these factors contribute to diagnostic delay. And this paper kind of wanted to evaluate that and analyze factors associated with this delay. So it was a two year observational study conducted in Bari, Italy. These were patients that were referred from either public or private oral Health Centers. 86 patients total with a diagnosis of DG who were ultimately diagnosed with either LP, PV or MMP. So that was like inclusion criteria. They had to have one of those three diagnoses. To be included in the study. And what they did with those three diagnoses is it was all one guy that made the diagnosis and then he just went back and saw, like, where were you referred from what, how, when did you first notice symptoms to when I made this diagnosis. So it was kind of like a, you know, relied a lot on sort of the patient sort of recalling some things. The average diagnostic delay was about 10 months. Table 1 examined factors associated with delay and things like sex or age or whether you smoked or drank alcohol. None of those factors contribute to diagnostic delay. But if you lived farther from a clinic, there was a greater delay. That makes sense. And if you went to a public oral health clinic compared to a private oral health clinic, you had a shorter delay. So those are the factors. I mean, that's not a lot of things that we can control. I was hoping that, I don't know, there'd be something in this that would help dermatologists, but really this is an issue of getting these patients with discriminative gingivitis. Like, if you're not going to take the time to like, work them up or do the biopsy or do what needs to be done, get them to a specialty clinic. And it seems like that happens quicker and faster in sort of public oral health clinics versus private dental offices. Not a whole lot for dermatology in this one, but again, it was a paper that I started because I like the headline and I don't know, I don't know if we get gain anything from this.
- [42:21]
A
Is it in Italy?
- [42:23]
C
Italy, yeah.
- [42:24]
A
So that's the. I think the biggest advice I would give is find an oral pathologist. Like look up the term oral pathologist. And if there's none of those anywhere even remotely nearby, then look up oral maxillary facial surgeon. Who are the people who are both dentists and doctors? Those are your best bets. We've got a guy in, in my group down in Cincinnati who's a. Both a dentist and a dermatologist. And he does like, he gives us lectures on oral disease names. Drawer Eisen, really cool guy. But yeah, he does is a dentist and a dermatologist. We need more dental dermatologists.
- [43:13]
C
Yeah, we had a dentist who was also a physician, Elizabeth Billido, and she left Pitt and that was a huge loss because she was the same thing. She was a dentist, but she had a medical degree. And they just understand oral medicine way better than just a person with a dental degree. No knock on them. I'm sure there's very good dentists that understand this stuff. But she would do the biopsies if they needed to be done. She understood the medicine behind it. She knew to do direct immunofluorescence testing and where to take that sample to get the diagnosis. That's a huge resource. And yeah, I don't know. I mean, you know, I don't know how many patients actually listen to the podcast, but yeah.
- [43:59]
A
What do you do gingival biopsies?
- [44:03]
C
I do, but not if I can avoid it. So I'll do a gingival biopsy if they're like, what, I traveled two hours. I heard you were a pemphigus or pemphigoid expert. What do you mean you're not going to do it? So I'm going to do the biopsy. It's very challenging. More often than not, like, I get a good sample that gives us an answer like, dur, you know, direct immunofluorescence for mmp. That's the big one. Because patients are just referred and like, I think they have MMP and like, there's no tissue, no biopsy. If they live close by, I will say, look, a dental specialist surgeon is going to get a better piece of tissue than I can. You know, I'll call them and we'll get you in soon. But if it's like they made a two hour trip, I'll do it. And I mean, it's just you, you get your needle in and you raise up a bleb and so you kind of swell up the gingiva and then you take like a 3 millimeter and just bury it like as far down as you can go. And then you get scissors and just kind of get underneath it and snip it. You try and avoid grasping the tissue, like with pickups as, as much as you can, because that's when you'll just obliterate the tissue. Or you separate the epidermis from the, or not epidermis. You separate the mucosal epithelium from the submucosal tissue. And the DIF is completely worthless at that point. So I'll do it. I, I do try and avoid it as much as possible, but sometimes you're just trying to help the patient and, and you want to give them an answer.
- [45:44]
A
Are you just. How do you make it stop bleeding?
- [45:49]
C
You give them, you roll up a piece of gauze and you jam it up there like big league chew. Remember they got that gum. You jam it up there and you say, I'll see you later. It stops.
- [46:00]
B
I think you can also use Dental rolls. Like, like there are these dental rolls that are like rolled cotton.
- [46:06]
C
Yeah, I make my own I, I homemade roll.
- [46:10]
A
It.
- [46:10]
B
It's a, it's like hand rolled cigarettes versus like marble red. Okay.
- [46:15]
C
Yeah. They, they appreciate the, the hand. Yeah.
- [46:19]
A
The provenance. Yeah. Okay.
- [46:22]
C
Yeah.
- [46:23]
A
All right, let's. We'll move on to my last two. So these were two, what I thought were phenomenally good articles. So first one we will do is about JAK inhibitors and ctcl. And so basically this was a article out of Europe. So mycosis fungoides, Cesare syndrome and systemic Janus kinase inhibitor is a real world retrospective study on behalf of the EORTC cltg, which I could look up what that stands for, but I know it means smart people who do lymphomas in the Europe. So they did a few different groups of people here. So they looked at like people with gvhd, people with myelofibrosis who got like JAK inhibitors for other stuff. But the patients that were relevant for us are seven patients who are initially diagnosed as atopic dermatitis. And so to just very quickly go through them. First patient had it for four years, went on up, diagnosed with MF six months later. Somebody who had it for two years went on dupy, then Barry, then upa, then diagnosed somebody else who had it for a year, went on Trelo, then abroad, Somebody had it for two years, went on dupy, then a Jack. Somebody who had it for four years, just went straight on up. Somebody who had it for two people at it for three years, went on upa. And five out of the seven patients had biopsies prior to treatment initiation that showed dermatitis and basically ruled out ctcl. But the, so the takeaway was, number one, a biopsy is not helpful or, you know, understandable that it doesn't, you know, to prove that it's not ctcl. So the thing was, this kind of goes along with the idea that we think with DUPY that it doesn't cause ctcl, it reveals underlying ctcl. And it's kind of been like, why are we seeing cases with JAK inhibitors? Well, now we are. It just took a little while for it to work its way through the literature. Again, no indication or one way or the other if it affects the prognosis. But. So what do you do about it? That's our next paper. So our next paper was a CTCL expert consensus. So this one was also out of Europe. So this one was cutaneous T cell lymphomas and dupilumab. For atopic dermatitis. A systematic review and expert consensus. So they had 37 experts, 18 were CTCL people, 19 were AD people. And I'm just going to tell you what their consensus recommendations were. So number one, dupilumab likely unmasks pre existing CTCL rather than causing it to that got 83% said yes dupilumab may worsen pre existing CTCL 80% said yes avoid dupilumab in known MF 100% said yes avoid dupilumab in mogamulizumab associated rash. Mogamulizumab is a treatment for CTCL that often causes a rash. You do not need to screen every patient prior to starting dupilumab. 97% agreement on that. They said do screen if AD onset is after age 40 94% said that do screen if no personal atopic history 97% on that do screen if atypical features meaning like a weird distribution or the rash doesn't look right 100% said that screening means. What were you going to ask? What does screening mean Exactly. So what? Here's, here's what screening means.
- [50:37]
C
I didn't, I wasn't reading ahead.
- [50:38]
A
Sorry. Screening means at least one biopsy that you request T cell clonality on. If next if erythroderma is greater than 50% BSA, add flow cytometry and peripheral T cell gene rearrangement. Reassess the AD diagnosis if a typical worsening on dupilumab. I think that's one of the ones that people often don't get is like if you put somebody on dupy and they don't get better, you should like, like rethink about it. Reassess the AD diagnosis if the rash changes during treatment reassess, consider another clonality workup. Stop dupy immediately if the CTC was confirmed. If it's non aggressive ctco, you can actually wait through three months before you decide if you do anything because it might just go away. If that was 91% agreed with that. If no improvement after watching weight start CTCL treatment 88% agree with that. I'm not sure what the other 12% thought. If aggressive features treat CTCL immediately 100% report it to the pharmacovigilance authorities 100% said that if biopsy is inconclusive close monitoring repeat in three months 100% said that consider switching to methotrexate 91% consider switching to phototherapy 97% avoid JAK inhibitors 85% avoid cyclosporine 91% and then build a dedicated database for these cases. 100% said that. So you need to start your own database if you see one of these people. But the things that there were no consensus on. Switching to Trello 50 is safe. 52% thought that was okay. Switching to Lebricizumab 61% thought that was okay. So this was.
- [52:34]
B
Why would one be any different than the other? The one person like went up to go get a cookie during the vote, I think.
- [52:42]
A
And if there. So the theoretical mechanism, if there is one, is that you push IL13 into the deep, the type 2 receptor and that may promote survival and proliferation of these malignant lymphocytes. And if that's the case, Lebry should actually do it worse than Trelo. So but the, this was one of the rare instances where like one of these Delphi things like this was actually super useful of like very concrete. Like, who should you screen? Do you need to screen everybody? How should you screen them? But should like it was, it was really well done, like really useful.
- [53:26]
B
Matt, do you know, like, if you go back for these people who, you know, end up with a diagnosis of CTCL and they had a biopsy and it did not look like ctcl. Do we know if you go back and do TCR gene rearrangements on them, do you find like, huh, look at that. It was there. It just totally did not present anything like ctcl. But those T cells were there just causing something that looked inflammatory. Do we not know the answer?
- [53:54]
A
I do not know the answer to that. I do not think that the answer to that is known in the. I know in the first one I talked about with the JAK inhibitors, five out of seven patients had biopsies beforehand. They did not like go back and run clothes clonality on them. So I don't, I don't know if there's like a time limit on how long they can like sit in formalin before you do that or like. But I have not seen that done anywhere.
- [54:21]
B
It would be really interesting to know the answer. Right? Like, that I feel like would help us get at like what did it unmask or was it, did it, you know, develop on. I don't know. I think it'd be interesting to know especially once they have a diagnosis of ctcl. You actually know what clone you're looking for.
- [54:38]
A
Yeah. And it's, it is a. As I was researching this or looking stuff up for this. If you now search dupixent and ctcl, you get ads from lawyers. There are a number of lawsuits now going on that, you know, basically they're saying Doopee hasn't warned people. And because they didn't warn people, dermatologists didn't know that if you didn't get better on dupy, it could be ctcl. Now they're also trying to argue, oh, it caused the ctcl. They're trying to argue it made the CTCL prognosis worse. But I was like, those, like into AI, I was like, those are both. We know for sure neither of those is true. AI was like, well, even though, you know it's true, they might be able to convince a jury and even if they can't convince a jury of that, they might try and say that since DUPY didn't make it a known warning, it led to dermatologists not knowing that they should do a biopsy if it didn't get better. So whether those will go anywhere or not, it seems to me like the kind of thing that is why everybody hates lawyers because like all of the medical science says that nobody has been hurt by this. That it. All that it does is make the CTCL diagnosable. Right.
- [56:05]
B
Right.
- [56:06]
A
Yeah. So that's it. Any other. Any last comments? No, no. I'm going to throw one more thing out there. I mentioned this guys to you guys, but I'm just so proud. My daughter, my oldest daughter Margaret got accepted into the Peace Corps, is going to be going to the Dominican Republic to teach literacy. And I will be going down once every three months to stay at an all inclusive resort and claim that I am there to visit my daughter.
- [56:36]
B
You're so supportive. Such a good parent.
- [56:40]
A
She wanted to go to Africa, but she got medically denied because she has asthma. And they were like, if you're in Africa in the middle of nowhere and you get an asthma attack, you literally could die. And she was like, okay, fine. But the Dominican Republic, they were okay with. So good.
- [56:57]
B
That's awesome. Congratulations.
- [56:59]
A
I'm excited. All right. I want to thank everybody for tuning in this week. I hope you laughed once or twice, hope you learned a few things, but mostly we hope you're planning to join us next week. And until then, I'm Matt Zyrus.
- [57:11]
C
I'm Tim Patton.
- [57:12]
B
And I'm Laura Farris. And we are derms on drug.