When the Data Get Personal

Welcome to season three of Derms on Drugs and Video Podcast brought to you by Scholars at Medicine the best education platform in dermatology and provided no cost and medical providers. Derms on Drugs is where cutting edge dermis in Miss Comedy. Dr. Matt Sires from Doc's Dermatology in each week and during my residency, buddies took to the Law of Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh and we use our 60 years of combined derm experience to discuss debate and dissect the hottest topics in dermatology. It is everything you need to know to be under cutting edge of derm and you'll have some fun listening. New episodes drive every Friday in Scholars and Medicine, Apple Podcasts, Spotify and other major podcast platforms and I highly recommend that you download the Scholars and Medicine app to access the full podcast video archive or the best educational term content out there. Not, you know, this farma driven what's the law that we're a new approach to know like actual coverage of useful topics right in all of dermatology supported by an amazing AI called Sotin 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. Ferris. What do you got? Okay, I have a paper that was published in JAD and this is the 40487 gene expression profile test guide systemic therapy selection to improve outcomes for patients with atopic dermatitis results from a prospective trial Jonathan Silverberg at all. Okay. 487 that's it 487 genes. I didn't even know that there were 487. But we only had like 250 genes total. It's kind of like the Baskin Robbins of gene expression profile. No, that was the F the other one. That's 31 flavor. Yeah, this is like I don't even know what has 487. It's like a video game or something. All right. Okay. Okay. 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 doopy or versus like who's going to do better on a jack inhibitor. So I think most people's algorithm is start with an antibody that if that doesn't work go to a jack inhibitor. But you know, we know there's probably TH2 driven atopic dermat and non TH2 driven. And so can you decide this, you know, a priori, can you decide this up front 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 invests you as a treating physician pit like, oh, I'm going to start you on, do you? Oh, I'm going to start you on, you know, this jack inhibitor. And so they enrolled 1181 patients. And this is, so this is just the AD paper. 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, he took a cure at scrape this lesional and non-lesional skin and did like some, some called RNA later. And then they did targeted RNA sequencing. 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 are 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 DOQI. 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 jack 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 and a given therapy class. And so they locked in that algorithm. And then they validated 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 jack inhibitor responder profile, about 70% had a TH2 profile. So if they looked at the jack inhibitor profile, the people who were like predicted to be jack 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 jack responder, you're going to do way better on a jack inhibitor. So if you're a jack responder and you get, do be only about 8% of those patients are going to have an easy 90, whereas if you're a jack responder and you get a jack 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 jack inhibitor, and they also did better on stringent endpoint. So 36.4 had an IGA of 0, 0% BSA versus none of the TH2, those people who were put on a TH2 targeted therapy. Also like more likely to have no itch, etc, etc. And the other notable thing is that everyone in that jack inhibitor responder group who hit easy 90 by three months did so on the lowest dose of jack inhibitor. So they didn't have to go up. How about the most of the people did have a TH2 profile? 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 basically are going to probably do about equally well on an antibody or a jack inhibitor. If you're a jack responder, you are going to do way better on a jack inhibitor than you are on an antibody. I thought that was interesting. I, my biggest criticism of this and maybe it's in there and I just did see it. There are some people in the top of your monetized 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. But how do you really feel? Patient after pay. Having done clinical trials and having a really good sense of what easy 75 looks like compared to easy 90. There's not a single easy 75 patient I've ever had who has wanted to switch trucks. 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 whatever, it's easy 75 is the endpoint that matters. Like they just for clinical care, E 75 is what matters. And I didn't think they reported E 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 Dan B from Yale did it where they did biopsies. And they showed that you could predict do be response based on essentially how much I'll 13 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. It's. 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 say that that beats having to do a skin biopsy in quantified aisle 13 right. I agree with that, but you should be able to do skin tape stripping for cytokine profiling. Yeah, but what's cheaper than than a cure. Right? I like the simplicity of this. It's not the cure. It's not the cure. You could probably do the cure writing as well for the cytokine profiling. The cost is in the gene. You're saying you're not saying it's the mechanism. You're saying it's look at aisle 13. Don't look at 487 genes. Yes, just look at like. Whatever it's cheap, but okay. Yes, that's the thing. Peter is cheap and it's what Castle's good at already. So I get it. And it makes sense. Like it's a good like, you know, I could see using it. 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, two thirds of the time it's going to say just start with an antibody, right? But let's say my patients who are on do be 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 leberchism ad, do I want to put them on nemozim ad, if I have 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 Trilow 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 jack inhibitor. I also like the fact that it also predicts that they're going to do fine on the lower dose of the jack inhibitor, which has a better safety profile. It's again, Ferris, you're being the smart one. That actually makes tons of sense to me, as a use at for doopie inadequate responders, if they're if they're an IL-13, they're not a jack responder profile, but they didn't respond to doopie, that probably means they're more likely to respond to, you know, leberied Trilow, 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. So yeah, it 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, but. Yeah, I thought the same thing. Like if you're a TH2 responder, like if you had that profile, then theoretically it'd be like doopie 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 doopie, only a quarter of patients really respond." Like that is not true, right? I mean, if you'd respond as, "I feel great, this drug's great." You know, I don't know what that objective measure is, maybe it's the easy 75. It's roughly easy 75. It's to leave in a little below easy 75, because when you look at drug survival, about 10% of people stop doopie because it didn't work well enough. 90% of stay on a long term. And the doopie failures, it's tricky, right? I mean, we had that atopic-dermond, like what matters to patients, right? It was safety. That was the biggest thing. More efficacy too, but that was the thing that patients. So if you say, "Look at, you're a jacky 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 lebry." 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 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 like incorporating this, like, do I see me doing it to. Like if I had the test, would I use it for a doopy failure? I don't know. I think I'd have that conversation first. And if they said, "I'm done with my eczema. What do you think's going to be the most effective drug?" It's going to be jacky. 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 lebry, even if the test said you're a jacky." I don't know. You know what it would be much better if they came out with a 487, 488 gene expression profile that predicted the risk of a heart attack or a blood clot out of jack. Then you could be like, "You know, if 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, they say, "You're no elevated increase risk of having a heart attack because of the jack inhibitor because we know that's just true for everybody." And go. So they could just add it in. That works. This. It's their baseline risk is what matters. Right? I don't know. I think that the reassurance of the lower dose is nice. I think that that's helpful. So I don't know. I thought this was good. I mean, you know, the people didn't get randomized to treatment, but I thought it was pretty compelling. It was just. I agree. All right. Pat, and what do you got? My first six-pack was published online January 2026. Jamma Durham. It's titled, "Methodrexane and Microphenolate Moffatill and Clinical Response in Juvenile, Localized, Sckleroderma by Deroces at All." There's a retrospective study of 114 patients with juvenile linear Sckleroderma. Treatment of JLS has, classically, been prednisone in methodrexane. It's a protocol published here at the University of Pittsburgh, 2012, by the senior author on the paper that I'm doing. Dr. Catherine Torrick. Do you know what Catherine Torrick, you know what name she goes by? Cassie. Cassie. That's a unique name for Catherine. I would have never guessed that. It's a good one. I like it. Yep. Retrospective study performed at UPMC Children's, 2010 to 2003. 114 kids with JLS. 68 patients on methodrexane, 28 on Microphenolate, 18 on both. Baseline characteristics are in table one. Most baseline characteristics were similar, except the Microphenolate group had a longer disease duration and a higher PGAD score. So when they're doing Sckleroderma, they do PGAA, which is activity or thema-indiration. PGAD is damage, atrophy, hyperpigmentation, things like that. So at baseline, these were not the same patients. As a retrospective study, Microphenolate, longer disease duration, higher PGAD scores. Table two shows treatment response as measured by the modified localized Sckleroderma skin severity index. And the response between methodrexane and Microphenolate was the same. No differences in flares of disease between the two groups. Table three examines adverse effects in methodrexane had way more of those, like 60% versus like 15 or something with Microphenolate. 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 methodrexane because it causes so much nausea. Did you used to have that problem with girls in high school? Yeah, this is on my like tender profile. May cause anticipatory vomiting? Yeah, and it's a big turn off and you know, my dating life suffered because of it. Looking at the bar graphs and figure two, it actually looks like methodrexane is better, like a higher proportion of improved, lower proportion of worsened. But I guess there were more MMM, Microphenolate patients that didn't follow up. So those numbers are somewhat distorted. Plus the Microphenolate had longer disease duration and higher PGAD scores. So if you look at those bar graphs and be like, okay, they say in table one, they say they're the same, but these bar graphs it really does look like methodrexane is better. A lot of that is just the larger numbers of patients and so the proportions are affected by that and also worse follow up in the Microphenolate. So that's it. I mean, you know, linear scleroderma, I think that is in a fair number of dermatologist 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 Durham. I think standard is that prednisone methodrexane sort of protocol that Dr. Torrick published in 2012. And I mean, that's a really nice paper. You talk about like, do picks and showing you how to taper prednisone in in BP patients. That paper that Dr. Torrick 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 methodrexane. 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. Torrick at this point is saying, Microphenolate's not a bad option and with just the high rate of adverse effects that was in the methodrexane group. Maybe we start there. Microphenolate is like systemic sclerosis, which used to be methodrexane, methodrexane. More and more rheumatologists are actually using Microphenolate for systemic sclerosis type, you know, like interstitial lung disease and things like that. They kind of like met, Microphenolate better than methodrexane. And I wonder if the same thing's going to happen in linear scleroderma. What do you guys think? Yeah, potentially. I mean, I thought that was interesting. I guess one, I don't think of methodrexane as being that hard to tolerate. I was surprised that the numbers. Kids. Yeah. Kids. Yeah. Kids, you know, they're so persnickety sometimes. They were probably just. They were just faking it to get some extra ice cream and screen time. But then fake it with Microphenolate. Now. Shut up. He's still being mean. Shut up. Shut up, he said. So again, the discourse, like you know, that's how you know it's somebody's really winning the argument. Shut up. Shut up. You're ugly. All right, let's move on. You make me anticipate poor vomit. Let's move on to my. 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, IL-31 blockade elevates TARC by lifting lamp 3 plus CD1C positive matured and and Drid excels from CGRP cows. the Ardeneroimmune Suppression in atopic dermatitis. This was in the Journal of Allergy and Tleglinology and here is the summary. So super cool. So they looked at four patients you had, Tennis Adverse Events from Memalizumab. So it's a common thing that people talk about, like oh, Nemo made my patients itch, like go away immediately, but their skin didn't get better. Maybe their skin even got worse. And it's always been like, why is that happen? Like is it just that it only works on the itch? And it doesn't work on the inflammatory components early on. Well, here's what they showed that in your skin, your itch neurons release CGRP, Cousin-Tonum-Gee-Ree-Lay-Peptide, and the CGRP keeps your dendritic cells in a naive state. And whenever you turn off the itch neurons, they stop releasing the CGRP, your dendritic cells, and it's one particular time it didn't drink cells, but who cares? Your dendritic cells now mature and start to make more torque. And torque is a cytokine that is thought to be one of the fundamental cytokines that is like upstream driving a topic dermatitis. And so it, if this could really explain it well because the expectation would be that the IL-31, if the lack of itch, if it's not working well on the itch, then it's not going to cost the torque to go up. And so it may actually be that the better it works on the itch, the more it makes torque go up. And so the more likely you are to have like this skin flare early on, that then it's 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 in their data is that they've seen it in 40% of patients. But the main takeaway is if once the reach is better, if you give them enough time, the torque comes back down and then they do okay, is at least the expectation. But just so-- - Can I ask you, what do you give? So I did some like the Nemo study. I'd probably 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? - Absolutely, I saw it. Yes, but they're itch was okay. Like they were not, you looked at them and were like, "Hmm, you're not getting better." And they were like, "Oh my God, I'm so happy, I'm so not itchy." If you just let it go, they will eventually their rash gets better. I had like 30 people in that trial. And it like you give them the time, it gets better. - 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? So 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? - Yes, that 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 catalogue. You know, I'm talking about, "Oh, there's steroids side effects in the blah, blah, blah." It would be reasonable to give them some cyclosporin or some Jack inhibitor. But I usually end up just doing a shot of catalogue. If they really want something with the majority of the time, they just give them a pack and they're not that bothered by it 'cause they're just so happy they're not itchy anymore. - Okay, that's great. - 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 a topic 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 is 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 a topic comorbidities? They do, Dupy gets a point. Do they have a history of staff infections? If yes, Dupy gets a point and add debris, Ebbglist gets a point, sabaco, rainbow, get a minus one. Words from a luscom, Dupy gets a plus one, sabaco, rainbow, get a minus one. But 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, subderm or is it a psoriasis form rash? Do they have significant facial involvement? Do they have a history of bichlorid disease? Are they highly needle phobic? Is there each 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 in order they have female of child bearing potential? And so those are all the factors that do go into this that I've always thought about. And, but the question is, 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 sims somewhere, scholars and medicines. So if anybody wants that, because it is pretty darn useful to just go through with the patient, like check, check, check, check. And then here's a score, like each drug gets a score and you can be like, OK, you scored best on number four. So it can be helpful if you are somebody who struggles with that. I think that could be really great for patients, just because like, you know, like you said, we try to give them all this information and they're like, I don't know, tell me what to do, right? 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. What kind of car should you drive? Will you get anticipatory vomiting? Exactly. All those kinds of things. And so I like, I think in 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. Yes. Well, it's only validated by Mads Iris, but it's OK. That's all I need. Well, in that paper, sort of is-- The paper doesn't give you a scoring system. It just is like here are the factors. But it didn't give you a like, here's how to use them. So that's-- That's OK. You're very compelling even without data. I think you can make it work. Wow. Thanks, Ferris. There? That may be one of the nicest things you've ever said to me. It might be. It probably will still remain that way for a long time. All right. Next study, Ferris. What do you got? I'm excited about this one. This one seemed really cool. OK. This is a single arm phase two study of T-VAC. Because I can't say the whole name, right? The talum-- yes, T-VAC. Inpatients with lower risk invasive cutaneous squamous, but fascinating. Just explain briefly what it is. Yes, Ferris. OK. What is T-VAC? It is a modified Herpes HSB1 virus that expresses GMCFF and is sort of modified so that doesn't have uncontrolled replication. So T-VAC is currently indicated, FDA approved, for the intrelusional treatment of melanoma mats. So usually like when you're using T-VAC, you're using it and advanced like cutaneous or deeper mats of melanoma. So this is saying like, what if we just use this in sort of a really lower risk disease, like low risk cutaneous SCC? OK. Mm-hmm. Yep. Single arm, single-site phase two study at the University of Arizona Cancer Center. Wait, wait, wait. I'm sorry. I know you did. I'm sorry for interrupting. No, I love it when you're at it. Please interrupt more. Explain a little bit. So it's just a modified, it's just like a weaker Herpes virus. Like, what is it? 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 HSB1 and I gave-- and I like injected a bunch of it into your skin. Like you get kind of a rippering HSB1. It could like, you know, spread, you know. It is modified to have like limit-- so that it really should only be replicating within tumor cells. Ah. So it's-- it's-- it's-- you heard me, OK. Got it. 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 cyclobiography needed to. OK. Got it. OK. OK. Eligible tumors, 0.5 to 5 centimeters. So up to decent sized tumors, well-demodderately differentiated, they could not have a thickness of greater than 2 millimeters. They could not have high risk things like perinermal or our vascular involvement. And interestingly, they did not treat ones that were on the face neckhands, nails or ankles. And each patient could have up to 5 confirmed invasive SCCs that could be treated as tariff. which they call TLI's, which are 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 a small study, 11 patients, 24 tumors, about 83% of those were, well, most of these were T1s in a few T2As. So the lesions averaged around 13 millimeters. So, you know, they could be up to five 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 TVAC. 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 just did like record review. Because one of the things they didn't just look at like to these tumors clear. One of the end points that 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 in 95.8% of tumors. So 23 of 24 lesions. And so one tumor was a partial response and stable. Median time 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 nuance thing, but I think important safety wise. Nobody dropped out from adverse events. So you know, TVAC does give you some people a flu like, you know, fatigue type syndrome. And they did see that most people's like grade one to handle with and says. And so here's where it gets, I think kind of interesting at two years after treatment. The number of new invasive ketaneous swamies per patient was significantly lower than both the one in two years before the TVAC. And so you looked at sort of, if you look at the sum of the two years, two years in one year before TVAC. If you look at all at squames, all squames, plus, or if you look at just invasive squames, 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 that and that P value was significant. So I thought that was interesting. And then non injected lesions. They had to, they had two lesions that had complete responses. So abscobal effect. So hypothesis generating interesting. But you know, this could be really helpful and where could it be really helpful like transplant patients, right? What did you call that the ad scopal response? Abscobal effects of 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 un injected tumor. And then you see 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 five or 10 or so? It was few. I'll find you the exact number in just a moment. Abscobal effect is described in radiation, right? Radiation oncology is probably where. Because you've radiated the tumor and you get lysis of tumor antigens. And effect on tumors that aren't irradiated. Never heard of such a thing. Like it's so it's kind of like whenever you inject the mother of work with Canada and all of their work go away. Yes, it is exactly the same thing. Abscobal effect. Abscobal effect. I'm going to start using that all over the place. There's a lot of places I can use that. So I think this is interesting. I think it is. You know, probably like there's a lot of interest now and intralesional therapy for tumor. So of course we know five FU met the tracks eight cutaneous squamous cells. 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, particularly is interesting, particularly if you reduce the number of future tumors or you treat more of them. There is an ongoing study that we are doing of interleasional submithlamab, the PD one inhibitor for cutaneous squamous cells. I think that's going to be interesting. There is a. Varica has an intralesional, um, an oncologic 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 and C or excision, probably not. But you know, like T that 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 PD one inhibitor where you're like, well, what if there's systemic impact and then they reject their organ. So I love the idea of this. I think it'll be interesting to see where the saw leads. I think that the long term data where because those graphs were pretty impressive like the coming down the number of lesions out the two years. Like that was cool. Like that's cool. I mean, this is just one injection into the tumor once or do you do it like once a month? No, they did several. They did them like, you know, I think up to like four injections per, um, per tumor. Okay. Okay. It's good stuff. 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 straight forward. Is it? No, it's not. So, um, so yes, like you have to, um, 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 Canada and start doing this, right? It's, it's going to be harder than, you know, interleasional methotruxate or five of you. But if you're a big center where, you know, you're already doing TVAC, let's say for melanoma and there are germs that do that. Then I think that this is going to be, um, I think it's going to be interesting, right? Another indication. Yeah. Cool. Yeah. I could really see it also being useful. You know, I think people struggle with the patients who have like, again, eight squames a year. Like in their, 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 squit like that. Super useful in those people. Yeah, and there were only, um, two target not injected lesions and they both got better. And they both got better. Wow. Okay. Yeah, I thought it was that, but I wanted to make sure. So yeah, interesting. Let's go pat and what do you got? Second six pack from the March 2026 edition of oral diseases titled diagnostic delay and discriminative gingivitis. An observational cohort study by cajulia at all. There was also an author with the name denta co, 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. No, but I know you're going to tell us an acronym. That's an actual real world. Real word, I should say. All right, some interesting points. What's a call. Like it's an apt name for you, acronym. Wow. Okay. Abscopal, acronym. Next week, we move on to bees. All right, some interesting points in the introduction. 85% of dentists report difficulties and diagnosing discriminative gingivitis. We're just going to call that DG. 93%. This is crazy. 93%. neither perform biopsies nor cons. I mean, that's hilarious, like not for the patients, but you can't make diagnosis of like LPPV or MNP 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, oh, you just kind of, I don't know what they do. - What do you say? Like just deal with it. I don't know what it is. I'm not gonna find out. - Come back for cleaning. - I think I could help you. - Do you want a fluoride treatment? - Use your fluoride and I'll see you in six months. - 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 LPPV or MNP. 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 sought like, where were you referred from? What, 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 one examine factors associated with the 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 discramid of 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 'cause I like the headline and I don't know, I don't know if we get gain anything from this. - Is it in Italy? - Italy, yeah. So that's the, I think the biggest advice I would give is find an oral pathologist. Like look up to a 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. And those are your best bets. We've got a guy in my group down in Cincinnati who's a both a dentist and a dermatologist. And he gives us lectures on oral disease and he's a drawer, eyes and really cool guy. But yeah, he does, he's a dentist and a dermatologist. We need more dental dermatologists. - Yeah, we had a dentist who was also a physician Elizabeth Bildo and she left pit 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 if you do - I'm gonna do a few patients. - Actually listen to the podcast, but yeah. - Do you do gingable biopsies? - I do, but not if I can avoid it. So I'll do a gingable biopsy if they're like, what, I traveled two hours. I heard you were a pemphagus or a pemphagoid expert. What do you mean you're not gonna do it? So I'm gonna do the biopsy. It's very challenging. More often than not, like I get a good sample that gives us an answer. Like 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 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 three 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 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 coastal epithelium from the subucosal tissue and the DIF is completely worthless at that point. So I'll do it. I do try and avoid it as much as possible. But sometimes you're just trying to help the patient and you want to give him an answer. Or you just, how do you make it stop bleeding? - You give him a, you roll up piece of gauze and you jam it up there like a big lead chew. Remember that got that gum? You jam it up there and you say, "I'll see you later." - It's not. - I think you can also use dental rolls. Like there are these dental rolls that are like rolled cotton. - Yeah, I make my own. I homemade roll it. It's like, it's like hand rolled cigarettes. - Yeah, like the Marvel Red. - Yeah, they appreciate the hand. - Yeah, the provenance. Yeah, okay. - Yeah. - All right, 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 Jack inhibitors and CTCL. And so basically this was a, article out of Europe. So my co-sus van Goides, Slesesary syndrome and systemic genus kinase inhibitors, a real world retrospective study on behalf of the EORTCLTG, 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 mylofibrosis, who got like Jack inhibitors for other stuff. But the patients that were relevant for us are seven patients who are initially diagnosed as a topic dermatitis. It's sort of just very quickly go through them. First patient had it for four years, went on OPA, diagnosed with MF six months later. Somebody had it for two years, went on Dupy, then Barry, then OPA, then diagnosed. Somebody else had it for a year, went on trail oath and abro. Somebody had it for two years, went on Dupy, then Ajack. Somebody had it for four years, just went straight on OPA. Somebody had it for two people, went it for three years, went on OPA. And five out of the seven patients had biopsies prior to treatment initiation. That showed dermatitis and basically ruled out CTCL. But so the takeaway was, number one, a biopsy is not helpful or understandable that it doesn't, 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 jack inhibitors, what 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 a Futanias T cell lymphomas and duplomab for atopic dermatitis, a systematic review and expert consensus. So they have 37 experts, 18 were CTCL people, 19 were AD people. And I'm just gonna tell you what their consensus recommendations were. So number one, duplomab likely unmasks pre-existing CTCL rather than causing it. That got 83% said yes. Duplomab may worsen pre-existing CTCL. 80% said yes. Avoid duplomab and known MF, 100% said yes. Avoid duplomab and Mogemulizumab associated rash. Mogemulizumab is a treatment for CTCL. some causes of rash. You do not need to screen every patient prior to starting DuPilla Mab. 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 rest, it doesn't look right. 100% said that. What's screening means? All right, guys, what were you going to ask? What does screening mean exactly? So what here's what screening means? I didn't, I wasn't reading ahead. Sorry. Screen means at least one biopsy that you request T cell clonality on. If a next, if a Rithriderma is greater than 50% BSA, add flow cytometry and peripheral T cell genuary arrangement, reassess the AD diagnosis if a typical worsening on DuPilla Mab. Like that's one of the ones that people often don't get. It's like if you put somebody in DuPi 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 DuPi immediately if the CT cell is confirmed. If it's non-aggressive CT cell, you can actually wait 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 wait starts CT cell treatment, 88% agreed with that. I'm not sure what the other 12% thought. If aggressive features, CT cell immediately 100% reported to the pharmacovigilance authorities, 100% said that. If biopsy is inconclusive, close monitoring, repeat three months, 100% said that. Consider switching to method trexate, 91%, consider switching to phototherapy, 97%. Avoid Jack inhibitors, 85%. Avoid cyclospor in 91%. And then build a dedicated database for these cases. 100% said that. So you need to start your own database if you see what it is people. But the things that there were no consensus on. Switching to trail-o, the safe 52% thought that was okay. Switching to lebrachism app, 61% thought that was okay. So this was what- - Why would one be any different than the other? That doesn't- - The one person went up to go get a cookie during the vote, I think. - And if there's so the theoretical mechanism, if there is one is that you push IL-13 into the type two receptor and that may promote survival and proliferation of these malignant lymphocytes. And if that's the case, lebris should actually do it worse than trail-o. But 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 it was really well done, like really useful. - Matt, do you know, like if you go back for these people who 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 implamatory. Do we not know the answer? - 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 when I talked about where the Jack and Hiveters, five out of seven patients had biopsies beforehand, they did not like go back and run clonality on them. So I don't know if there's like a time limit on how long they can like sit in four-bellen before you do that or like, but I have not seen that done anywhere. - 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 clonier looking for. - Yeah, and it is a, as I was researching this, you're looking stuff up for this. If you now search duPixant and CTCL, you get ads from lawyers. There are a number of lawsuits now going on that, you know, basically they're saying, dupe hasn't warned people, and because they didn't warn people, dermatologists didn't know that if you didn't get better on dupe, 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, like, into AI, I was like, those are both, we know for sure, and it was just 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 duPi 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 all that it does is make the CTCL diagnosable, right? - Right. - Yeah, so that's it. Any other, any last comments? - No. - Right, I'm gonna 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. It's going to be going to the Dominican Republic to teach literacy, and I will be going down once every three months to stay in an all inclusive resort and claim that I am there to visit my daughter. So. - You're so supportive, such a good parent. (laughs) - 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." She was like, "No, okay, fine." But the Dominican Republic, they were okay with. So. - Good, that's awesome. Congratulations. - That makes sense. All right, I want to thank everybody for tuning in this week. I hope you had laughed once or twice so if you learned a few things, but mostly we'll hope you plan on to join us next week. And until then, I'm Matt Zyrus. I'm Tim Patton. - And I'm Laura Ferris, and we are Derms on drugs.