[music] Welcome to season two of Derms on Drugs and Video Podcast brought to you by Scholars and Medicine, the best educational platform in dermatology and provided in no-cost medical providers. Derms on Drugs is where cutting-edge dirt meets, and hermit's comedy. I'm Matt Zires, and each week I'm joined by my residency buddies, Dr. Laura Ferris from University of North Carolina and Dr. Tim Patton from the University of Pittsburgh, where 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 on the cutting edge of Derm and you'll actually have some fun listening. New episodes drop every Friday on Scholars and Medicine, Apple Podcasts, Spotify, and other major podcast platforms. To remind everybody there is a video component which has some of the key figures and tables from the articles that we talk about. So this week we've got another one of our patented six-peck episodes where we are going to go over what is the coolest, most interesting new stuff in the literature from our perspective. Dr. Ferris, why don't you start us off? All right, Matt. I'm going to start with Merkel Cell carcinoma. Everybody's favorite neuroendocrine skin tumor, I know. So this was actually a good question for you too, first of all. If you had the ballpark it, how many Merkels have you like actually seen in your real life in your clinic patent you first? One, Ferris? I have diagnosed two and probably like followed about five or six patients. I follow a couple of Merkels, but like, so I mean, I'm doing the bio city of North Carolina in my first six months here. Okay, it was all my differential. So it made me look like I knew what I was doing. Okay, I always put it on my differential. Yeah, I've never diagnosed one. Yeah, we did. I feel like this is Merkel. You never know. Talked about a ton, but they're just pretty darn rare whenever you really look at it. But all right, Ferris, go ahead. Yeah. Okay, so this is GONNAL at all. This was in JAMA dermatology. And this is polyoma virus antibodies for Merkel cell carcinoma recurrence detection. So this is Paul Nemes group in Seattle. They are sort of like the gurus of Merkel cell carcinoma. And so they have really like specialty Merkel cell. That's all I think that Paul does as far as I know. And they really have the largest patient population. So they are kind of like my go to experts for Merkel cell carcinoma. Okay, so credibility. Yeah, credibility. So they ran what I think is probably the most, you know, comprehensive study on Merkel cell, polyoma virus, onko protein, antibody titers for Merkel cell carcinoma surveillance. So do you know what those are Matt? I do now, but I didn't like four days ago. Yeah, yeah. Okay, so basically, you know, we know that interestingly overall from the study about 80% of patients with Merkel cell carcinoma, Harbor Merkel cell polyoma virus. About 80% you said about 80% of the pension actually do. Now in this paper, 50% of patients had the antibody, but when they went back and looked at all of them, there was sort of this 30% group that was antibody negative. But when they, you know, looked out their tumor, they could actually identify virus in there. So that's where I'm giving you that 80% number. Okay, so Merkel cell polyoma virus. Basically, you know, we all have MCV, most of us that we that that's like it's around. It's just it only kind of integrates in and causes Merkel cell carcinoma in a subset of patients. It turns out that you said we all have MCV. Merkel cell polyoma virus. Yeah. Okay. Sorry. Got it. Merkel cell. Okay. I was like, we all have a mean corpuscular volume. We also have that, but that's yeah. Go ahead. So we've all got the virus, but most of us. So most of us have been exposed to the virus, but it doesn't, you know, we don't have Merkel cell carcinoma. Okay. So, so anyway, what happens is that when you are when you have the virus that integrates and causes the cancer, it exposes this neoepetope and you make an antibody to that so that antibody is a marker that says, yes, you have Merkel cell carcinoma that is virally driven. So this can be useful in following patients. So they don't, so even though we most of us have the virus, we don't have that antibody. Okay. All right. Good. Okay. So 503 patients with stage one to three Merkel cell carcinoma were followed for a median of a little over four years. They had blood tests every three to six months, measuring titers of this antibody. It's called a Merck. It is a test. By the way, you can order it. If you, you know, search a Merck, you can order it at the University of Washington. So you can, you know, order the test. Your patient can get a drawn and they can send it off. So anyway, what they found in the study. So, you know, they followed patients from diagnosis and then every three to six months. And so what they found was one, the higher your baseline, a Merck titers, the higher your chance of recurrence. They also just sort of, they also found that if you are a zero, that was not what I took from that graph. So the, that was baseline baseline. Yeah. So probability of recurrence free survival. If you were seropositive, you had a higher probability of recurrence free survival. And if you were seronegative, you had a lower probability. So the, the answer, it was good to have the antibody. It's good to have the antibodies, but when now we're talking for the people who are positive, what is your tighter? Oh, so the higher your tighter, so you want to be positive and low tighter. That would be the ideal. Yes. So in zero positive patients, so the people who have the antibody, having a falling or negative. So, so having falling titers. So either a negative tighter. So we're talking now when we do our doing surveillance throughout your course. Having a falling tighter or going to a negative tighter predicts like over a 99% chance of being recurrence free for three months and like a 98.8% chance of being recurrence free at six months. So low tighter is good. And then on the flip side, if you have a single rising tighter, your risk of recurrence goes up to like 36% and three months are up to like 68% in two years. So, so you know, basically you following these titers, it can be really helpful. Because it lets you know like, who do I need to worry about and who do I not need to worry about. And I think sort of the end game of this is if your tighter is falling and you're you go to particularly if you go to a negative tighter, you could potentially avoid getting, you know, CT scans or pet CT scans in that situation. The tighter that the rising tighter also was helpful because it flag recurrence before clinical or like image based detection and over half the cases with immediately time of about four months. So rising titers were not always like immediate imminent recurrence. But they did suggest that you were at risk of recurrence. And then this they looked at it sort of like on a protest basis and also on a per patient basis. So you know patients who had substantially higher risk of recurrence. So they had a substantially higher risk of recurrence after a rising tighter versus with a following tighter with it like a hazard ratio of like 51. Okay, so yeah. So then the other thing that was kind of interesting is that the same group recently had an ASCO abstract where they also looked at circulating tumor DNA and a mark in the same patient. So two different biomarkers CT DNA is circulating tumor DNA. Now that's going to be, you know, you that's not virally dependent. So Merkel, so carcinoma that is virus negative can also have, you know, will also shed tumor DNA. But what they want to do is look in the patients where they could follow both. And so they had 171 patients over 700 paired samples in that group that 38 recurrences. So what they found was actually that a positive CT DNA was actually sort of a more ominous or worse prognostic factor than a positive a mark test. The hazard ratio for recurrence was over 27 was CT DNA versus 5.8 with, you know, rising a mark. So CT DNA positivity was more strongly associated with recurrence. This is an abstract. So if you're going to ask me like every last graph. You've already told me more than I wanted to know. Okay, one year positive predictive values 73% for CT DNA versus in that series 51% for a mark. So putting that all together. It is, if your patient has a falling or negative a mark tighter, very reassuring, you could probably, you know, you could probably space out their surveillance. And I'm going to be the one necessarily doing this probably for the average term. No, but I think it's nice to know. And I also think it's helpful. You know, why do I think that this is helpful.
test that we can order. And you know, particularly if your oncologist wants to be, wants to use this, which many of them probably do, you can at least send out, you know, order the A-Mark test, send the patient. So when they go to see oncology, they have a baseline. And I think that, you know, time is kind of of the essence when we have these tumors. So, you know, I thought that that was sort of helpful, you know, what kind of imaging the authors said that they generally do PET CT because it's more sensitive. And that is their preferred imaging if it's available CT scan if you can't get, you know, PET CT. So it's kind of the liquid surveillance era. All right. All right. So the quick summary, when you're diagnosed with the merkle cell, it's good if you've got the antibodies, because you got a higher overall survival there, ready to be getting. But then once you've got the merkle cell, you want your titers to be stable or falling. If your titers are rising, that's bad. And if you've got tumor DNA in your blood, that's bad. You got it. All right. Pat, you got anything you want to add? No, but right. I mean, I think on call, like for us, we have a merkle preferred a hemonc maybe think about checking that A mark. Although last patient we had with this, like we like that we couldn't do that. Like our own send out lab. Our send out lab was like, what are you talking about? And then, and so it was like six months before we figured out how to do it. And they do recommend that that A mark initial test be done within three months of the initial diagnosis. Because if you cut out merkle, like if you're the one excising it, titers like drop pretty quickly. I think within, like I think they said about within a month of starting therapy. Do they get moose or do they get wide local excision with the sentinel lymphedobiopsy? A ladder. Everybody gets, well, yeah, and CC and guidelines, everyone gets sentinel node. Yeah. There are most people that take out marker. Okay. Yes, the guidelines would say, so I think that's actually a good take home point for, you know, the derm not practicing in a big multi center, you know, oncology or big, you know, oncology center. You don't just send these patients to moose. They really need to go to surgical oncology. Everybody should get a sentinel node biopsy. If you remember nothing else, remember that. All right. They could go see moose, but I think it's part of a multidisciplinary, like, decision. Yes. I'm not think moose cannot be the removal, but you don't want to just say moose. You don't need to sort of enter the surgical oncology path. Agreed. Agreed. Okay. Let's move on, Pat. I can't wait for you to talk about this woman. When you, when you put it in the thing and I was like, oh, but I know a study that shows that collagen, but then I was like son of a, yeah, well, so that's the problem. Not that I have a huge interest in collagen supplementation, but this is the stuff. This is like the walking out the door questions where patients are like, what's your favorite sunscreen or what do you recommend for this? What do you recommend for that? And get it. Hey, what do you think about collagen supplements? So I was reading in the Wall Street Journal a few weeks ago, because you guys know I am sophisticated and I saw the headline, wonder pills or waste of money, the new supplements promising youth and beauty. And of course, my first thought was like, it's a huge waste of money, of course. But none of the healthcare providers interviewed said it's a huge waste of money. For some reason, they interviewed two people who are co-founders of the companies that make the supplements like that. Why would you do that? Yeah. There was one dermatologist at the end of the article who said, if you only take the supplements for a short period of time, it is going to be a waste of money. So this shot, Derms on Drug Shout-Out to Dr. Halty McDonald. I think he practices in Austin. Wall Street Journal, that was not my six pack, but it was just a little clever lead in to introduce my first six pack, which is titled "Effexive Collagen Supplementation on Skin Aging, a systematic review and meta-analysis of randomized controlled trials by Young and Park." And it was in the American Journal of Medicine September 2025. I just read the Wall Street Journal article when I came across my six pack articles, so it could not have come at a more timely time. Why even do this study? There were already two meta-analysis of randomized controlled trials that showed collagen supplements, improved skin hydration, and elasticity. We don't need to do anymore. We've proven it. It works. This particular meta-analysis sought to perform the meta-analysis focusing in on study quality, as well as funding sources for the individual trials. 893 records. They got down to 23, included over 1,000 patients, conclusions, collagen supplements, work, people. They actually work. They significantly improve skin hydration, elasticity and wrinkles. I think I'll introduce one of my own and retire a gazillionaire, except on neither clever or hardworking enough to found a company. So that's not going to happen. So now we can comfortably tell our patients to start taking collagen supplements, right? No, because that study showed that it was only in the industry sponsored studies. Exactly. So the author drew through. They went through and did some subgroup analyses. Couple of interesting subgroup findings. One subgroup they looked at the source of the collagen. Fish collagen worked. Cattle or chicken collagen didn't. Pills and powders. Not effective. Machine-a-ming. You need to take collagen drinks. Fish collagen soda. Yeah. Mountain EW. Casting. Come on. What is the worst beverage you could ever have? Yeah, you vomit. You vomit a lot, which helps with weight loss too. But the most interesting subgroup analysis looked at funding source and study quality. If the study was not funded by a pharmaceutical company, it didn't demonstrate any benefits. If the study was a high quality study, it did not show any benefits. And they had these quality metrics that had been accepted as established measures of quality. So I am telling my patients that collagen supplements are very likely a waste of money. And with everyone on TikTok saying how much better their skin looks because of collagen supplements, I know my advice will have no effect whatsoever. What do you guys think? I'm still going to be telling people to take the one that I like is called Verisol, V-E-R-I-S-O-L. It's not a brand. It's an ingredient. Mainly because it is extremely cheap. So it's like six bucks a month. You get a jar of the powder. It's three months worth for 30 bucks or something. It's like 10 bucks a month. And they have themselves funded trial. It is randomized double levels. It could drool, but it was funded by them. So now I'm. Yeah, so I had a couple of observations concerns. Number one, if an industry does the study, and I don't think they're making shit up, like I think they're doing a randomized double-wide placebo controlled study, why is it that their studies work? And if a non, like somebody just goes in and says, I'm going to look at this study, I'm going to look at this supplement on my own, and it wouldn't work, how are they doing this? Like consistently from this paper, how are they able to show that their stuff works? No idea. It could be sample size, right? You can afford to do a bigger study. You can also afford to pick multiple different endpoints if you're an industry study. It takes time for me to do these things. So a few episodes ago with Dr. Tarrbox, we talked about the hair supplements. And I went back to those studies. Every single one is industry funded. So whatever the supplement was, if you looked at who funded the study, Viviscale, Neutrophal, even the Pumpkin Seed Extract, they're all industry. So is this probably true across all supplements that are not like drugs and don't have to go through the rigorous FDA sort of process? My sense is, yeah, probably. I don't know. I still like my creatine. I think it works. I believe I create. A creatine is different. So creatine actually has a fair number of independent evidence. Wait, I did look at that because I'm a creatine person too. I started doing that. What's a do for you? Bill muscle increase, decrease fat weight, increase muscle weight blah blah blah. Okay. Okay. Well, I'm still going to be believing that industry sponsored trials for supplements. I'm still it's yeah. Yeah. I'm only recommending things that have a marketer behind them because they're the only ones that work. No, I'm going to recommend it by by price. That is absolutely my defining factor is if it's pretty. Right. Because maybe this helps very little downsides to taking a collagen supplement. I mean, you know, they have the radio tracer rat studies. I mean, ingested collagen does make it into tissue. You know what I mean? But does it actually show any clinical benefit? We don't know. So if you're going to spend money, go go with the cheapest. Okay. All right. We're going to move on to my part of the six first part of the six pack. Your own personal six pack. That's right. I get great. What are you talking about my core again? Thanks, Ferris. Well, I was talking about it. It's hard not to. So
Yeah, I first got some topicals here. So first two that I don't really want to talk about, but just put out there, granulomane ULARA, topical reflumalast worked. My main thing there would be, and that was a case report, I think oral reflumalast should be first line treatment for GA in general. But if you could get topical covered, which you won't be able to, it worked. And then granulomadast rosacea, case report of that responding to tapineroth. So for both arrow hydrocarbon receptor vatama and PDE4 receptors or reef, great, some kind of pain in the butt things that they work for, but that didn't really matter, and I could be able to get them covered. Now, let's get on to what's actually interesting here. So Ruxilitinib and Believerna, I was first author on this article. So Ruxil, - So we're voting on the problem. - Uh huh, I'm part of doc-starmetology, D-O-C-S dermatology. I want, how much of the article did you actually physically write? - Done, but I, but I, I, I put together an outlet, so we had a phone call, and I made, and we did a detailed outline that was kind of the draft, and then when they, you know, then they put it together, and then I, like, like very carefully read it, made tons of changes and recommendations and the whatever. So I did a lot. I like, all right. - I believe it. - I believe it. - Yeah, it wasn't like they wrote it, and I like signed off on it. Like, there was a lot of work. So the main takeaway here. So this was efficacy and safety of Ruxilitinib cream for the treatment of moderate to severe chronic hand-examine, results from a 16-week multi-center, randomized double-blind study. So this was Ruxilitinib versus placebo, good old obsulara, and their IgA success rate was 53%. So we can say most people, and so, so the big thing about this study, though they excluded anybody with a topic, Derm. So it was supposed to be primarily, you know, a hand-examine of unknown etiology. So probably a mix of AD, sorry, allergic contact, irritant contact and endogenous. But if you had a topic, Derm, it was a preexisting diagnosis, you couldn't be in the study. So they, they, right now. - Right, so my big thing is chronic hand-examine is a topic, Derm. Like, it always has been. - So like that, right? I would argue that chronic hand-examine is always irritant contact dermatitis with either superimposed, with, you see, their ICD plus AD, or ICD plus ACD, or all three. But I, 'cause right, if somebody came in and said, with AD, and you said, well, tell me about your bathing, and they said, I get six showers a day. You would say, well, you've got some irritant dermatitis. Let's see if, you know, maybe that's what's going on here. And since we wash our hands six times a day, I think they all have some irritant dermatitis. So right, and this gets it, you're getting into the problem with hand-examine. It's like, should, if it's not ICD or ACD, should we just call it AD? And I kind of agree that's a yes. But in a lot of the pharmacists, they talk about it. They're only gonna call it AD if they have AD affecting other areas. All right, so. And I think AD is not all one disease, by the way. Young people who get it, and they don't have one. There's a different group than the old itchy people, but all OOD, but different flavors of it. Yeah, I guess if somebody came in with chronic hand-examine, they never had a top-derm anywhere else. It's like, all right, you're washing, you have to say they're a cook, right? Yeah. That's where you can see chronic hand-examine. You're working with food, you're washing your hands. I know none of the other cooks have chronic hand-examine. So why do you have it? Because you probably epigenetic change, and to keep it simple, an epigenetic change in flagrant in their hand. So it's etiologically. That's a example. It's etiologically. Etiologically, it's a topic term. It happens to be localized to your hands. Yeah. I'm so baffled by this chronic hand-examine. So they're like a first and only treat. I have a lot of things that I can use to treat chronic hand-examine. That are FDA approved to treat chronic hand-examine, because it's etiopic term. It's-- I would argue that it is always-- it's always an overlap of multiple types of dermatitis. It's either pure ICD, or it's AD plus ICD, or ICD plus ACD. ICD. We're talking irritant contact dermatitis allergic contact. Yes. And the reason that matter-- About how that soup here-- And the reason that matter so much is that-- Matters is more than anybody else out of-- It's very clinically relevant. So topical steroids make irritant contact arm worse. So they relieve the symptoms, but they make your barrier function worse. So you stop making lamellar bodies, and you stop making intercellular lipids. So while it's clubatus, all will make irritant contact arm feel better, and makes interline disease worse. And the key thing with obsulara and in zupco, the new delgocidinib, specifically, approved for chronic hand-examine, is that they don't have that adverse effect on the barrier. So you're much more likely to actually get people better with these than with clubatus. Now, I've had the heads to prove that. But if clubatus won't work great for hand-examine, they wouldn't have been so excited to try and be pursuing this. But let's back to the study here. So Rux, IGA's success rate of 53%, versus 11% for placebo. So most people got to clear or almost clear. Now, the big question-- so Rux, hexi-75, hand-examine severity index, 80% of people got 75% better, versus 27% with placebo. How does that compare to in zupco? In zupco had an IGA's success rate of only 25%. But there's a very good reason for all of this that I'm going to get to. It only had a hexi-75 rate of 50%. So by sheer numbers, it just looks like it's not as good as obsolera. But number one, the two trials use different IGA scales. So clear or almost clear for the obsolera trial could have redness and or scaling. So very minimal, barely visible scaling for the inzupco trial. You can only have barely perceptible error theme. If there was one flake, you were mild. So that is a big difference. Number two, the delgo trial was done only in Europe. The obsolera trial was done in Europe and the US. And this was one of the first hand-examine trials in the US. So none of us knew how to do the hexi scores very well. And then finally, the Rux trial excluded people with preexisting known atopic derm and delgo didn't. And the people with known atopic derm were some of the worst responders to the delgo, to the inzupco. So to some extent, in the Rux trial, they almost weeded out some of the hardest patients. So these is really a case where I don't-- although by sheer numbers, I would say, it just looks like obsolera was bad. You truly cannot-- this is a situation where we're looking at different diseases, different endpoints, very different trial populations and investigators. You really can't look at this and say that obsolera is better than in zupco. You can just say both work for hand-examine. It probably ought to be like, which one is easier to get? Is probably what should be driving, which one we prescribe. And does the patient have atopic dermatitis too? If they have atopic dermatitis too, you should use obsolera, which you say that. I would say that I think that whether they-- I mean, if they have atopic dermatitis as well, I guess you'd give them obsolera. But in a practical sense, I think they're pretty much identical drugs with the exception that the inzupco doesn't have any propylene glycol in its vehicle. So that-- Narcola? So yeah. Do you anticipate Ruxilit nib pursuing a CHE indication? I don't think so. Yeah, it wouldn't make any sense. Yeah, I don't-- it'd be-- like I've always told that company, like just-- I'm comfortable saying that if you've got a hand-examine, there's a component of AD to it, unless it's pure allergic contact or where, OK, try to change into a fragrance, try using only CERN-V hydrating cleanser. And if your hands get better than fine or change your gloves, but if treating it as allergic contact term doesn't get them better, then I'm comfortable calling it AD already. So why spend hundreds of millions to get another indication? It's kind of going to pose a weird situation, which I don't anticipate. It'll actually be this clinically difficult. But say you really want inzupco. You've seen the data. You're like, yes, this is perfect chronic hand-examine. There's this FDA-approved drug. You have chronic hand-examine. And the delgo, it doesn't get them any better. And then you're like, I want to actually give you systemic medication. Your hand-examine is so horrible. I think Dupy's really, really going to work well. We're just going to have to change your diagnosis to a topic term. Whereas from the get-go, it would be just like this is a topic term. There's a hand-examine predominant, or maybe exclusive component to it. It's just weird. I think what's going to happen is that in the end,
initial diagnosis, you would call it dermatitis unspecified, treating with ends up go. And then when they didn't get better, you would say, okay, it's not unspecified anymore. Now I think it's a topic. You don't get these letters like there is no diagnosis of chronic handexema in the chart. Like I get those. I mean, not specifically CHE, but intrinsic atopic dermatitis. You just called it a topic dermatitis. Maybe it's just the insurance environment in Western Pennsylvania. If you're going for an AD drug, you gotta say it's AD of the hands, which I think is true and most cases, generally true, there's no way to prove it's not. And if you're going for CHE, I think you call it dermatitis unspecified of the hands. But probably both like really good drugs, right? Yes. I will never have a head to head, but I guess would be that they're going to work the same. In theory, it is important that it looks now like they both seem to touch tick two, because tick two seems to be more important for irritant hand dermatitis than Jack one and Jack two. So just an interesting thing. All right, let's move on to our next article here. Dr. Ferris, what do you got next? So I went from the most serious to the least serious. So I have efficacy, safety and recurrence in subariet dermatitis, a dose dependent analysis of oral isotretin Owen, 10 milligrams versus 20 milligrams. This was this paper was in, I didn't write it down, so this is in JAD. It's JAD. So I picked it because it was like an investigator initiated study, a drug that we use a lot of something we all see every day and because it was done in Turkey. And because the first author and the last author have the same last name, Demir Boss. Okay. That's a good Germany. It is. It is like the boss of Durham. All right. So what they did was this was a retrospective study of 234 patients who were treated with oral isotretin Owen, 10 milligrams a day versus 20 milligrams a day. So kind of half and half, a little more with the 10 milligrams a day. For a minimum of three months, but an average of 4.2 months in the 20 milligram and 4.5 in the 10. And interestingly, we're more likely to be on the high dose and patients who had had subderm longer were more likely to get 20 milligrams. Why did they pick to treat subderm with isotretin Owen, the oil thing would make sense. Why 10 or 20 milligrams? I have no idea. But they did. So what did they find? What do you think works better? Higher dose, 20 milligrams. Higher disease control, DL, QI, patient satisfaction, all better with 20 milligrams. The probability of being recurrence free. So we get to talk about recurrence free survival across both of my papers, but very different context. At one month was 83% on 20 and 42% on 10. And at a year, it was 36% from the 20 group and 14% in the 10 milligram group. So adverse events, amazingly, they said there was actually more like myalgyz and epistaxis in the 20 milligram group. I feel like that's, but interestingly, the 10 milligram group had more dry lips and skin. I feel like that's all kind of putting up. Like nose bleeds for the 20 milligram. It was 40.7%. That's an insanely high number for 20 milligrams of isotrope, no, and I intentionally eliciting it. Like it probably wasn't like ER nose bleeds. Yeah, I just like when patients on acne doses of acutane are complaining about dry lips and my nose is dry and I'm like, all right, we're going to go down to 10. You're not going to have any of those side effects and you're just going to have to take it for a year. And you're right. Maybe I'm not listening to those. Well, how many is your dryness better or what it's just, those numbers were surprising to me. What do they do over there in Turkey? Yeah, I don't know. I don't think I've ever done like 10 milligrams a day of isotretinone for anything. But so, you know, there's probably a lot of select. Acne patients are some acne patients are like just can't tell. Everything's dry. But my, so the, all right, takeaway was seems to work while you're on it. Yeah, it sort of works while you're on it. If you're going to do it, go big or go home and, you know, like there's no waste, no weight based dosing here. Yes. So, you know, what's your anotoline average size? I don't really know. So I wanted to throw out that adjective. So, yeah, I got out in the poolines all the time. I know. For those of our listeners who by context, I'm believing anotoline means Turkish. Yes. So the one thing this reminded me to throw out there is don't forget that for somebody who's got subacus hyperplasia, isotretinone is actually a very effective therapy. So there's some data out there, 40 milligrams a day for two months, really shrink some down. And they probably eventually do that. We whenever I've used it, they do eventually come back, but it can be like five years before they come back. The subacus hyperplasia. I think it's better for that than for subgarb. Agree. I agree. That is good. I've had that with like renal transplant patients who have been on like type of linus and gotten lots of subacus hyperplasia. So, yes, that's the take home message. It had nothing to do with the paper. All right. One. Next study, Pat, and what do you got? It is from August, 2025 issue of biomedicines. I don't think I've ever read anything from biomedicines. So excited. Actitic key lightest, systematic review and metanalysis of interventions. Treatment outcomes and adverse events by Al Fartsy at Al. Some general background information on actinic key lightest just for, you know, general info. It is considered a precursor to SEC of the lip. I don't know why I wrote that down. It's of 3.2 to 16.9 to invasive SEC. So, AKs probably over treat. I'm not worried about most AKs. We could probably leave them alone without any significant consequence. This is in, of course, the non transplant patient. Actinic key lightest kind of worries me when patients come in and they have like the scaling and the cracking and this doesn't heal and you look at them and you're like, this is probably a actinic key lightest. I think probably deserves to be addressed more so than just run of the milk, katanias, AKs. Lip SECs have a higher metastatic potential compared to katanias SECs. So they went through this 2,000 records. After screening exclusions, they included 36 studies in the final exam. I get to the point. Efficacy was determined by clearance rates and recurrence rates. I was like metanalisized out at this point. I don't understand anything from metanalysis. They talked about generalized linear mixed model. That's it. I'll talk about that. Let's talk about that on. What works and what doesn't work. So, I assume that the thing is clearance is what's the likelihood it's going to get rid of it and then recurrence, what's the likelihood it's going to keep it from coming back. Right. Two forest plots that pretty much lay it all out. CO2 laser and mico mod had the highest clearance rates. Figure three, forest plot for recurrence rates. Once again, CO2 and mico mod come out on top. So I guess those are the top two most effective options. This wasn't anything that was surprising, but I hadn't read anything on an actinic lightest in a while and so it was nice to reassure what I always thought. The problem is that most germs don't have a CO2 laser on hand. And so there have to be a referral and one time I actually referred a patient with biopsy proven actinic lightest to get CO2 laser because I knew this other office had it and they sent the patient back saying this isn't actinic lightest. So that was a little frustrating and the problem which I know and it was just a dry light. It was the weirdest thing. I didn't know what to say to the I'm like I feel really bad. I mean, if it's biopsy proven, we sent them the path, whatever. Maybe it doesn't. Maybe it doesn't get reimbursed and the patient didn't want to pack it. I don't know. Maybe I missed something. The takeaway would be ideal treatment according to this then is a mico mod more so than 5FU or other stuff that is accessible to us. So 5FU didn't even have a study. So it wasn't included. I think there was a study in the recurrence, but there wasn't an efficacy. And the problem with a mico mod is like I would never use a mico mod. If you use field therapy on the lip, it is an absolute disaster. Those patients like wind up in the ER with swollen, cracked, painful, can't eat lips. So I don't know what to do. What if you just, so what I would do is, unless they've given regimen here, I would be like,
like, okay, try putting it on just once a week for a couple of weeks. If you didn't, it's not a disaster, then try going like Monday, Thursday. And if it's not, that's probably the way to go. It was interesting. So it was two studies that looked at the efficacy. So I went and looked up the studies. One of them, they did it daily for eight weeks. The other used it three times a week for four to six weeks. And both papers said, when it got too bad, they told the patients to stop. And conclusions from both of the authors that did those two separate studies were like, we need a different regimen. These reactions are absolutely terrible, but they just kind of left it open. So I think you're right, Matt. I think like if you're gonna use topical, it is just gonna be the wimpiest sort of regimen that you would ever do. - Right. - Like once you try to do whatever. - Yeah, what I actually did with that patient is I did cryotherapy. That was not part of the analyses, but we have that, that's easy to do. You can actually freeze the whole bottom lip. I actually did it in like thirds. The patient tolerated it well as well as you tolerate any AK freezing. And it worked. She came back, the cracking was gone. It finally healed. She was very happy. - Why'd you do it in thirds so that you could charge three visits? - You know, absolutely. That's why I did it. (laughs) - No, it's a secret. - And I prescribed a medication as well, like TAC. - So you could get a level four. - I could get it up to a two, one, four. - So you did a third of a lip at a time so that she could still eat through the other suit, whichever part of it. - Yeah, I thought it was a tolerance issue. I was a patient's first man with me in stomp money. - The other thing that would be interesting here, of course, we've talked about how we think, how the data seems to suggest that five FU, Cousapetraine combination is highly effective in as long term efficacy. That'd be another option to think of to use as a like, okay, try it a couple of times a week to start, blah, blah, blah. - How does what I do? - Okay, do you do it with like, - Specifically, - Very well. - Fruity or any key lightest? - Yeah, I have to, yes. I will do it for actinacillitis. Everything's brutal with actinacillitis. - Do you have from paper up with it or do you, what do you do? - I just say, do it, I tell them they can do it for like five days and I'm like, if it just becomes too bad, just stop. - So five days and then you're done or five days are on, then-- - I'll say five days and then you're done. And then, they all bring them back in a few months and see-- - So why not do like five days a month, like five days, like do it for five days, then next month, do it for five more, the next month, do it for five more, then come back? - I feel like you gotta just sort of see these, do something, tell them do it. You're gonna, it's gonna be really bad when it gets bad stop and then let it heal and then come back and let me see. I feel like it's so tailored and individual with actinacillitis. - Okay, okay. - Not that I want listeners to know like, how bad my skin is, but I did that combo on a little AK above my eye. Like for five days, I was a mess for like two weeks. I mean, people coming in are like, oh my gosh, what happened to you? - Huh. - Well, I like-- - Okay. - Yeah. - Maybe I'm just a sensitive person. - No, you know you're sensitive Dr. Pat. - Thank you, we know. - All right, let's move on to my second batch here. I've got one main one that I want to get to that a couple of quickies. Some more amicwamod. So this was just a study of radiation versus amicwamod for difficult lentego maligna. Main takeaway was that amicwamod 5% Monday through Friday for 12 weeks tailored to putting it on enough so that they got air a theme without pain. So increasing or decreasing, 92% success rate in treating lentego maligna. So really an interesting, two thirds required an adjustment of frequency or they didn't get air a theme with five days a week so they had to go at a retinoid or occlusion but tailored it to where they got some irritation but not where they had, you know, however frequently you had to. So up to five days a week. So big question here. So this is lentego maligna, not lentego, right? So I wasn't exactly sure if these were invasive or not. I don't think they, I think they did invasive or not invasive. Do you guys offer this for lentego maligna or do you tell people to go get mose or what do you, like to me, this probably ought to be our first line treatment for lentego maligna. It's a discussion. I think each lentego maligna is like its own discussion because if it's small enough and it can get mosed off, that's generally going to be the answer. If the patient is super old. If you have a more surgeon, who does it? Yes, this is why everyone should stay in academia because then you always have that. No, but it is, I think it's just a discussion, right? And like there are 99 year olds who, like we should maybe do nothing with. Like it's so individualized. I have a hard time saying this is my protocol for lentego maligna. Pat, what do you do? Yeah, if it's a lentego maligna in a patient who will tolerate surgery, then I biopsy it and I send them to surgery. And if it's a lentego maligna in a patient where you're like, man, they would not tolerate surgery. A lot of times it's because that patient just is not in great shape. And so you don't even biopsy it. You just kind of say this probably is lentego maligna and it's not unreasonable to just kind of watch it and make sure it doesn't become anything more. But I suppose if I did the biopsy and it came back with the diagnosis, I write, like Ferris said, you have the discussion. We don't need to do anything because these are not aggressive and we can follow it. If the patient's not gonna tolerate surgery, you have these two options. The problem with both of those options is, radio therapy's not great 'cause they have to go in for like, what was the average 13 treatments, right? So I could see the family saying, we're not gonna do that. And then applying a MicoMod little packets and putting it on twice a day. Once a day. Once a day. Once a day for 12 weeks, they're not gonna do. You know, is the compliance gonna be good there? It's like, there's not a lot of great options. And so you had the discussions and if the patients are like, I wanna do the easiest thing for me, it'd probably be a MicoMod. And we can at least tell them that, hey, numbers are good. Do I expect them to be compliant with this particular protocol? Not really. - Okay, all right. All right, my other two quickies. So a prema last in the treatment of central centrifugal secretarial alopecia and open label pilot study. So there's 20 patients, 15 patients finished it. Most of the end points were somewhat better at 24 weeks. It wasn't like, woo. But I said that when I read this. - Why? It was like, woo. (laughing) - It's serious. - I think like, right now zone or something. Or yeah. - So it at least gives us, you know, it suggests to me that oral reflumalas would work well since we know oral reflumalas works better than a prema last or at least we strongly think that and it's cheap, right? We say, try and get in some oral reflumalas plugs every episode, $6 a month and Mark Cuban's Cosplus Pharmacy last time I checked and works just as well as a prema last. Listen to some of our prior episodes about dosing. - I'm going to bring you on that like, what's this show? What's the show? - The sharks are all on shark. (laughing) - Maybe you could suggest starting a oral reflumalas company. And he would invest in it because everybody would buy through it. You could market, you could have a speaker's bureau. - Sure. - I think I see where you're going with this. - Yeah, that's I'm working on it. The iris you see me a little unstable and for that reason I'm out. (laughing) - All right, and then my last one, this was actually in the Journal of Investigative Dermatology. So big time journal, this was actually a commentary about the real article, "Druggs and Bugs in Atopic Dermatitis Benefits to Skin Microbiome from Target Immunotherapy's. Maintain, they did four different arms, Jack and Hibiter, one arm, Dupy and other arms, like sport and other arm, Topical steroids and other arm. And basically what they showed was that Dupy and Jacks improved the skin microbiome in addition to improving the disease, whereas cyclosporin did not improve the skin microbiome. Because it's been an interesting question of, now Dupy improved it more than the Jacks. And that makes sense because I'll 13, whenever it signals it reduces the antimicrobial peptide production, that's why you get covered with staff. And so Dupy, since it blocks out 13 more densely than Jacks, it improved the microbiome more, meaning it got rid of more staff than it Jacks. But what this really showed to me since cyclosporin didn't do that was that getting rid of the staff isn't just because the disease got better. The drug does matter. And if, so if you've got somebody who's got AD and getting a lot of infections, probably IL-13 inhibition, we don't have any evidence that one of the drugs, Dupy versus AdBree versus Ebbaglus, we don't have any evidence that one of them is better at getting rid of staff than the other. But I've seen more data for Dupy in Trello, or sorry, Dupy and AdBree than I have for Lebbury, Ebbaglus sorry, but I imagine all three of them equally benefit your microbiome since we know that IL-13 inhibition helps to get rid of staff.
That's the main, that's the takeaway. Any, the other thing that was interesting here is before I forget, I learned what quorum sensing means. I've been reading that a lot of microbiome, gut microbiome studies. So quorum sensing is the one, say, particular species of bacteria gets dense enough, gets enough population density, then they can detect each other, realize, hey, we've got enough of us here that we can do something. And then they start to secrete proteases or toxins or form a biofilm or whatever. And so just an interesting thing that if you've got a little bit of staff, it may behave completely differently than if you've got a lot. Because once you get a lot, it then senses quorum and starts to make these proteases and toxins that damage your epidermis and directly as a protease and drive inflammation as a toxin. So that was interesting too. It's like that scene in Gladiator where they're like together, we can survive and they all get together and then they fight off the things that come out of them. That's right, all those chariots and whatever. Yeah. How many times a day do you think of ancient Rome, Pat? A lot, like every day. There's a history of Rome podcast. It's got like 270 total episodes and I listened to the whole thing and then I started it over again and started listening again. So quite, quite more than anyone that I know well wants me to. Okay. When do you listen to them running, exercising? Oh, nice. The one right now. Oh, actually. It's way better than our podcast. If you're listening to ours, I advise you to switch over to that. I want to let everybody know that when I listen to our episodes, I listen to them on like 2x. I can't. Oh, my gosh. Do you listen to either of you listen to any podcast at regular speed or do you always speed them up? I'm a 1.5x history. History Rome, I listen to. Okay. 0.75 so it goes on longer. All right. Well, you know what I was going to say is that the microbiome thing, it actually reminded me of like the hand exima with the jacks, right? It's like there's more to it than just calming down the inflammation, right? And steroids hurt the barrier and that's why it can be okay, but like jacks may be way better. And it's just a difference of cyclospor and dupy. You have good responses to cyclospor. You've had these a talk of creation, you can cyclospor and they're like, okay, yeah, it's not better, but it's not the, this has totally changed my life that you get with dupy. And I wonder if it's because it's it's addressing more than just the inflammation. It is addressing microbiome and, you know what I mean? In the itch sensitization, right? So the I/O 13 that is I/O 4 and I/O 13 that are expressed on itch neurons. So you're calming down the itch neurons, you're fixing the microbiome, whereas cyclospor and it's kind of doing those things, but it's only doing them by removing the inflammation. It's not actively improving antimicrobial peptide production or reducing the hypersensitivity of the itch neurons. That's interesting. All right, well we are going to wrap it up there. So I want to thank everybody for joining us this week. If you got, you know, questions, comments, ideas, you can shoot us an email at
[email protected]. I hope you learned a few things. I hope you laugh once or twice, but mostly I'm hoping you plan to join us next week. Until then, I'm Matt Zyris. I'm Tim Patton. And I'm Laura Ferris and we are Derms on Drugs.
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