[music] Welcome to Derms on Drugs. A video podcast brought to you by Scholars in Medicine. Derms on Drugs is where cutting-edge dirt meets low grade to mediocre comedy. I'm Matt Zieres and each week I'm joined by my residency buddies Laura Ferris and Tim Patton where we use our 60 years of combined Derm experience to discuss debate and dissect the hottest topics in dermatology. Everything you need to know to be on the cutting edge of Derm and it'll be the most fun you've ever had while actually learning something useful to an end every Friday and visit us at Scholars in Medicine, Spotify and Apple Podcasts. So let's go ahead and get into it. We've got a special episode this week so we're going to cover six articles that we thought were the most interesting in the literature in the recent weeks and we are going to start off by jumping right into Dr. Ferris with our first article. Dr. Ferris, take it away. All right. So the paper that I have is in JID Innovations and it is, I'm going to totally butcher the name Magliquitas at all but this is surgical debulking, modifies notch signaling and may improve vismodagib effectiveness for locally advanced basal cell carcinoma. So this is not a huge study. Wait, for just a second there, I was like, when you're like, I'm going to butcher this where I'm like, it's surgical, the first word is surgical. Like how are you going to put that was wrong with you? Okay. I could do that. Okay. So basically this is, this was four patients. So this is sort of a small proof of concept but these are patients who had locally advanced basal cell and you know, that's a term that gets thrown around a lot since we've got drugs approved for it. What's locally advanced and it's like, I don't know if it's like half your a les that locally advanced. I mean, these are like locally advanced. These are big tumors if you look at, you know, in the paper. So like five, six, nine centimeters. Okay. So you've watched the show, the last of us, is that the one with the fungus that comes out of people? That is what this woman's back looks like. That's exact. I thought the same exact thing. It is just it's a fungating lesion. I do not watch TV like you to do. So I will take it at your. We're not running. We're not running. We're not running. Yes, right. We're not chairs. Exactly. Exactly. Yes. So, so four patients locally advanced, basal cell, debulking, then vismodage. So after so after they're debulking, they got a week later, they got a punch biopsy so they could look at the tissue. And so what they found was, you know, interesting, just that process of the surgical sort of trauma from debulking, really upregulated, you know, a bunch of sick like notch and went signaling associated genes like patched and hay to and, you know, other other genes. But what was really impressive was the clinical response in these patients. So way better than you would think. So basically three patients had a significant clinical response. One was lost to follow up like a typical, luckily advanced basal cell patient. And then about a year later, one of the patients needed surgical intervention. But you know, we think about like, I think we traditionally think maybe I'll give them a bit of a bit of a bit of a shrink down that tumor, then I'll do some surgery. But this actually suggested that it might make sense to debulk it, then put them on medication, and then bring them back and think about doing surgery. And again, the idea is that the debulking causes the tumor to express stuff that makes it more responsive to the chemo. That's the idea. Yes. Yeah. So it actually makes it more likely to respond than if you didn't do the surgical debulking. I think we still need more data on this. But you know, and how much surgical debulking do you need to do? Can you eat, and see? But I like the idea of, you know, sort of this idea of sensitizing the tumor was something that's relatively straightforward. Yeah. I always thought sensitizing would be like a mikro-mod or, you know, the T-vec stuff that we were talking about, you just go in there and just shave it all down, right? Right. But what I wondered here is when they debulk this, how did they get it to stop bleeding? Like with that, I guess that new. Lots of hotter. Lots of aluminum chloride. The patients all have Alzheimer's now, but it's okay. They get their BCCs are better. I had a BCC. That's not. BCC's specific quality life is great. We're all going to get dementia whenever we're. We've even. We deserve it. We deserve it now. Right. All right, Pat, so the takeaway there, unlike one of our prior episodes where we decided that a miccuritage followed by a mikro-mod, not dermed on drugs approved, does look like pre-vizmodegeb debulking, provisionally approved. Provisionally approved. A weighting a study of greater than four patients. You know what? With RFK having gotten approved, we might be the new FDA. We could just. For all of dermatology. We could be the new FDA. Prove, not a. No, next. All right. All right, Pat. My first six-pack was a pre-proof article from the November, jad of last year titled COVID-19 Infection is associated with an elevated risk for autoimmune blistering diseases. While COVID-19 vaccination decreases the risk, a large-scale population-based cohort study of 112 million individuals, wordy, wordy title. It's by Kerman et al. In the intro of the author's refer to a meta-analysis from 2024, suggesting COVID vaccine could be associated with new onset or exacerbation of A-I-B-D autoimmune blistering diseases. So what do we tell our patients? I had patients with new onset BP after getting COVID vaccine and they would say, "Well, the booster flare might be P or not and I'd be like, maybe, and I'd be like, maybe a will or maybe a won?" And I'd be like, "Yeah." No, I needed a better answer than that, believe it or not. It was a retrospective cohort study that used trinetic software to study millions of patients in the United States. So starting date of January 2020 up through, I think, like May/June of 2024, three groups of patients diagnosed with COVID. These were received the COVID vaccine and control patients. So just had a health encounter without any documented history of COVID-19 or vaccination within six months of the index date. They then performed propensity score matching came up with three comparisons. So thought was, COVID-19 infection, it's going to be worse than controls. You get an infection, your immune system gets all fired up if it's getting to scientifically technical. I apologize. You get A-I-B-D as a result, right? And that's what the first forest graph shows, figured to a patient diagnosed with COVID-19, 50% more likely to develop an A-I-B-D as a result. Stronger association for PEMF is compared to with BP. Hasaratio for PEMF is really high. Hasaratio for BP was lower, but it was still statistically significant. Top three plots, primary analysis, authors did a bunch of sensitivity analyses. I'm not going to get into that just for a sake of time. The next forest plot is COVID infection versus vaccination. That's figure 2C. Overall, hazard ratio of 3.13, higher hazard ratio for PEMF is really high, like 5.5. So 5.5 hazard ratio of the infection versus vaccination of giving you an A-I-B-D, right? So why did I skip over figure 2B? Because it's the dramatic effect. This is the most exciting part of the paper, right? Like I said, I don't get out much. So figure 2B, COVID vaccine versus controls, risk of developing A-I-B-D was almost halfed by getting the vaccine compared to control patients. And that was surprising to me. You would think, you know, between a control group and the vaccine, vaccine is going to ramp up your immune system a little bit. And it's probably going to be a higher risk of A-I-B-D in those patients. And the opposite was true. It was mostly the result of PEMFIGUS because the hazard ratio for BP was numerically lower in the vaccinated patients, but it wasn't significant. So if patients are asking about COVID vaccine, will it increase my risk? You can tell patients we have one study. And it showed that with a particular condition, vaccination actually appeared to be protective and so take that RFK vaccine protected. So what is extended PSM? That's one of the things in the. So you propensity score match because you say, okay, I want. I need somebody who's white, who's the same age, you know, same ethnicity, same age. Few co-morbidities, I think their first PSM was. Okay. and the teen use, things like that. They just extended it. Liver disease, chronic fatigue. Yeah. But better matched than normal patients. Yeah. Matched them for more co-morbidities. Huh. This is. It's mechanistically really hard to think of how this, and yeah, I know you've mentioned this already, but it's hard to think of how this is possible. It just-- - Except the vaccine is, so I don't know that with trynetics, you're capturing every COVID positive case. - I think that, right, I think that explains it, right? These aren't controls in the sense of, didn't ever have COVID, right? They never saw their doctor about COVID. They never took a COVID test. But I mean, everybody got COVID. - Yeah, they could have taken it home, and they just, yeah. - But still, even if you think about that, you're comparing, so that group of patients, those control patients would be, okay, got COVID, but really weren't that sick. So basically didn't have significant immune activation. Whereas the, I mean, some people got pretty sick getting the vaccine. And again, remind me, was it that COVID was COVID compared with vaccination? Which one was, COVID was worse than vaccinated? - COVID was worse. - Or Pemphagos, they had that 5.5 hazard ratio. I mean, COVID was way worse, especially for Pemphagos, but it was worse for BP as well. - So anyway, it goes back to the answer we can always give, why did I get this? I must have been a virus. Your immune system responded to a virus and it just got overworked in the whole thing. So it confirms for us, we can just make up, continue to use the virus excuse for everything. - Thanks for the easy. - So first, I think of you as our psoriasis expert, did so as the dermatitis guy, I saw tons of people who believed that their dermatitis got worse either after COVID or a COVID vaccine. I don't know. Like I would always agree, 'cause I was like, "Oh, you know your body better than me." You think the time it was right? Sure, I could imagine that. Did you feel like you saw that with psoriasis? - Not as much. Everybody just wanted to get an excuse to work from home 'cause they were on a biologic. That was my entire COVID life as the psoriasis person. - Would you give out the, I'll give an excuse for almost anything, 'cause-- - I know you well. - Yeah, it's generally easy. - I'm not that nice. Haven't you figured that out? - That's true. It's true, I will agree with that. (laughing) All right, so let's go on to my first article. So this one was just fascinating to me. So, right, diet and living environment is novel, ideological factors for melasma results from a retrospective case control study of 150 Chinese patients. First author was last name, Xi. And the things that jumped out at me here. So they looked at a lot of different aspects and some of them were a little bit odd like you remodeled your house, you didn't remodel your house, like whatever, I kind of weeded those ones out as hard for me to come up with any plausible explanation. But the things that were really interesting. So if you had an abnormal menstrual cycle, you were more likely to have melasma, okay fine. If you had a previous sunburn or exposure to sun two hours a day, you were more likely to have melasma, okay fine. Regular sunscreen user was more likely to have melasma. Now that's one that I think is probably reverse causation where people notice, maybe they're getting some bigmentation or something, so they start using lots of sunscreen cream. It's hard for me to buy that one. But the one that was most interesting, I'm gonna throw in one more that just kind of so cystic breast hyperplasia, so which I think is a hyperestrogenemic state, sure, melastrogen is a million of the type of response of, but alcohol intake. Now the number of people who were significant alcohol consumers was relatively low in the study, but the relative risk of melasma for people who consumed meaningful amounts of alcohol was 24 higher. And so it does now, whenever I see a patient who's got melasma, I am gonna ask them if they consume alcohol and I'm gonna recommend to them if they do drink and I'm not even talking like excessive drinkers, I'm just talking they drink. I'm gonna recommend to them that they cut that out as much as possible. 'Cause again mechanistically, alcohol has a lot of effects. I can imagine that it increases blood flow to your skin and that increases heat to your skin and that increases pigmentation, something like that. A lot of imagining. A lot of imagining. You're drinking their alcohol outside in the sun while remodeling their house and found it. Which is not safe, you should not be drinking anymore. Yeah, don't do that. So while getting a mammogram to find your cystic hyperrelasia, who knows? So there were a few things that protected. So, sebrary dermatitis patients were less likely to have melasma. People who drink soft drinks, less likely to have melasma. Let's see here. And then that was a vitamin C effect, right? Didn't they say a lot of the soft drinks have the vitamin C? Well, so I'm going with caffeine because coffee intake also reduced your risk of melasma. Interesting. So I'm going with, don't people use caffeine and skin brightening topical things too? Why didn't you even think about that? Yes. I thought the moving to a new place was kind of interesting because they said in the paper, when you move, most of the time you're moving like to a nicer place or you're moving like out of the city into a more sort of like not in the city and they felt that maybe the higher pollution and things like that in the city affected. It was an interesting paper. I mean, I, the alcohol interesting, maybe you'll mention it. I'll probably mention it. Right. Because I was looking for like what can I talk to people about? Because I'm not going to be like, well, did you move? Oh, you're shutting up. Like what? Do you remodel your house? Yeah, go back. Go back to your old place. So, but the alcohol things useful and then the caffeine intake I can buy that, we know that coffee has a lot of, there's a lot of data that coffee is beneficial for decreased cancer risk, decreased dementia. I can't remember decreased something. So maybe, you know, coffee intake might be good. But all right, that was our primary takeaway from there. So let's, let's alcohol maybe more coffee for your malasmapatients. And let's move on to our next study here, Dr. Ferris. All right. So this is the impact of antibiotic therapy in psoriasis patients with active streptococcal infection, a prospective study. So this is the journal of dermatology, bond, clanny at all. So this was, you know, we all-- - Wait, wait, wait. It was, it was banchiani. That's an eye not a nail. - Banchiani, okay. Okay, thank you for cracking. - Banchiani, banchiani. - Okay, a banchiani, okay. I was just reading it. Okay, so we all are taught, you know, strep infection is associated with psoriasis or guttate psoriasis or psoriasis flares. So they kind of tried to answer that question, but they had 155 psoriasis patients, and then they had, you know, sex matched dermatology patients who didn't have psoriasis at about the same period. And what they did was they came in, they did a throat swab to look for strep, and then they checked ASO titers. And so the patients who had strep infection with psoriasis received both topical treatment, which was basically beta-metamethasone calcibetrile, and an oral antibiotic, which was like a moxacillin or chlorythromycin or clindomycin. And the people who didn't have strep, they just got the topical. So they included strep infection as positive ASO or a positive throat swab. So these are not like people coming in with terrible sore throats. It's sort of just like did we find evidence of this. So, you know, I think the thing that was interesting was 25% of patients with psoriasis had a positive culture. Half of them were ASO positive, whereas only about 13% of healthy controls were positive for that. So more evidence of strep in the throat or positive ASOs and psoriasis patients. But they really did not see any, they didn't see more improvement with like antibiotics didn't make these patients do better. Now, they didn't have a control group. They decided it would have been unethical at an asymptomatic person who they happened to swab and have a positive test to not treat them. So they didn't have a control. Like, okay, this group gets antibiotics. This one didn't. So, you know, there was maybe some, the patients who got antibiotics, there's Pazzy scores were a little bit lower, didn't reach statistical significance. It, I don't feel like this really gave me a whole lot of answers, but, you know, interesting. I thought the most interesting thing was just higher prevalence of positive throat cultures. - And you guys, neither one of you does sort of empiric a moxacillin or anything else in your guttates or ASOs patients. - I don't. - No. Didn't Cress and English teachers did that? I feel like that's what we didn't resume.
I don't, I mean, Cress maybe, I don't think English, like if you weren't symptomatic, but maybe I'm misremembering. I don't remember. It was very traumatic training under him. No, no way. I'm putting it up plug. The two greatest dermatology educators in the history of dermatology were Joe English and Doug Cress. It's right. Amazing. We wouldn't be here. We wouldn't be there. We wouldn't be here without any normal people would have rejected all three of us. So we're very lucky. I'll still never forget that day when I found out my God, there's a DO coming to do residency with me like what? Where has my life gone? And it turns out patents. You've just lost your whole DO audience. Thanks. There's a, it's a, I had a story in the end. I can't do it. It was a stereotyping that was, I'd learned my lesson. Like, And this is the smartest of the three of us. Right. Interesting the strapped thing. You know, there's some data that like tons electomy may improve surrises. So there might be something there. I just think this wasn't the way to get out of it. But you know, I forgot about that. I've had some old dermatologists tell me that they had patients back, you know, back in the day when we didn't have like amazing drugs. Who they really saw tons electomy's not everybody. They didn't like tell their patients go get your tonsils out, but they had their experience over a long time was that a tons electomy made a substantial number of surrises patients surrises much easier to treat. Yeah, which is believable. It's believable. Okay. So we want to our next patient here. Our next study. So Dr. Patton, want you go ahead? Yeah. Second six pack was January edition of seminars in arthritis and rheumatism titled use of biologic drug in the treatment of localized sclerodermin systemic sclerosis in children, a scoping review by center et al. Why did I pick this? Because I do manage linear sclerodermin in adults from time to time, not kids, but I figured it would be relevant. My treatment algorithm combined steroids and metatrexate may be at my caffeine late somewhere down the line. So I saw the title and I'm like, huh, biologics. Like in my this, you know, prednisone metatrexate kind of old fashioned am I missing out like are there biologics I need to start thinking of this is the age of biologics. Even though the article discusses both localized sclerodermin systemic sclerosis, I was just going to focus on the linear scleroderm apart. Systemical arros is often managed by room. So it was a review that was conducted on 29 articles. Text goes through a bunch of numbers and the tables are hard to understand they were for me. I'm not that smart. Almost all the patients were on or had been on corticosteroids and metatrexate and a lot of patients also tried my caffeine late. So it still looks like those are first and second eye agents for localized sclerodermin main points. There was a visual abstract most preferred biologic was a betisept 55 point two of patients a betisept is orrencia second most prefer. What's it do? Do you know what it's thing? A betisept is it's a CtLA4 protein hooked up with IGG. So the CtLA4 protein binds to CD80 and 86 on the antigen presenting cell. Basically not letting the antigen presenting cell interact with the T cell and activating it. Blocks costimulation. Thank you. I could have said it blocks costimulation. So it's like the opposite of the cancer chemotherapy drugs. Yep. Okay. All right. I got it. All right. Second most preferred drug was tosaluzumab. That is an anti-IAL6 antibody. That was used in 48.3% of localized sclerodermin patients. Main indication for using biologics was progressive skin disease. So it was kind of you know, derm relevant. That's why they did it most frequently is because they were on some of those other medications and the skin disease was getting worst. They list these improvement rates of betisept. 92.9% tosaluzumab. 77.4%. But like the number was really confusing for a betisept. The response rate was only reported on 33.3% of patients. So close to 70% of patients didn't have data on whether they improved or not. It's really hard to say that like you know, 92.9 like oh my gosh, that works awesome. But they didn't have data on 70% of the patients that were you know in this review. So tosaluzumab data was available for close to 90% of the patients. So even though the improvement rate was lower, that number might be a little bit more reliable. I don't know how helpful this article was. It reassured me steroids and methotrexate probably still the way to go. If you're not getting that response, maybe consider a betisept or tosaluzumab. But I've never given those drugs. So I don't know how easy it would be. They're not FDA approved. They have both been evaluated in controlled trials. There was a phase two multi-center randomized, a betisept published in 2020. The primary endpoint of an improved skin score wasn't reached or it didn't reach statistical significance. Let me say that right. And then there was a phase three trial tosaluzumab also published in 2020 primary skin fibrosis endpoint wasn't met either. So I don't know. What do you guys think? Well, the adult ones you're treating are they in kudasab or are they like over a joint or could be any of it? The last two that I treated, like I said, I don't treat a ton of this, but it was over. It was linear over a joint elbow hand affecting range of motion. Yeah. Okay. I do. I'm mostly sending these patients to rheumatology when they're at that point of like more needing more than methotrexate. Room is it can be weird though, right? I mean, some the last one I saw had seen room and the room to have their specialty. So they saw like maybe it was a DM specialty room person and said linear scalar derma's dorm like go and see them. Yeah, I guess I'm not given a betisept or tosaluzumab. No, I that's yeah, yeah, I get that point. I'd be working with them, but yeah, that's interesting. Maybe I'll think about it more. Yeah. So Pat, I got asked there was this beautiful cord diagram. Yeah, I know what it's gorgeous, but what I can't make heads nor tails of it. It was really about indications. And so it's easier if you go down to like infleximab where there was like one patient on infleximab or maybe it was retoximab. And the cords go out as why was that person given infleximab where there's three little cords to three different of indications progressive skin disease. Maybe it was pulmonary. So it was basically that whatever drug it was being attached to the indication for that particular drug. Honestly, I think that's why I picked the paper. That thing was I want to I want to get that on a t-shirt. And then I would wear it and people would come up to me and ask me about my cool t-shirt. That might happen. Yeah. All right. Patten easily dazzled. Pretty colors. That's that's to take away. All right. Let's get to our last paper of the six packs. This one was mine. As regular listeners are probably starting to figure out we are big proponents on Derbs on drugs of oral reflumalast. So this was a real world 24 week perspective cohort study. And really there are a couple of things that were useful here. So first how good is this drug. So oral reflumalast for anybody again who doesn't know about it. Think Otesla, but free and more effective. But also probably a little more GI side effects as the way that I think about it mechanistically it's identical. It's just higher potency as a PDE for inhibitor and went generic about a year or two ago. And so it's it's about six bucks a month. If you get it through Mark Cuban's cost plus pharmacy. No labs. No immunosuppression. So this was people who went on or reflumalast. And how many of them the key things here were how many got past 75 and how many got past 90. So if if we look at the past 75 it was over 50% of people. So it was between 50% and so between half and two thirds got past 75. So if we looked at it as observed it was modified in or I would basically as observed it was two thirds. If we looked at it as non responder imputation and to treat analysis of his half. And for passing 90 it was somewhere between a third and a half. So depending on how you look at the stats. So a good drug actually had better numbers there was a randomized double blind study or at least a randomized blinded study where they looked at method intramuscular method. Trekseid versus reflumalast and actually got more like 75% of people to pass 75 and about half to pass 90. So just goes back to another thing this is a really useful drug. If your patient has been on a biologic before they're probably not going to be happy on it because it's slow does give you some GI upset and doesn't work as well. But it's incredibly inexpensive no immunosuppression is very safe drug and so using it for psoriasis gives us the main reason I think it's interesting is it gives us an idea of how effective it is. The main places I'm using it are more like in planis granular a like in planopilot areas.
stuff like that where we don't have better drugs. And then occasionally in psoriasis, whenever I can't get a better drug covered, anything that either of you wanted to add about this. The main reason I wanted to do it was just it gives us again more of an idea of how effective this drug is as a general idea of how well is it going to work for L.P. or whatever. I like it. People say, "Oh, I like to add a Tesla to biologics." I can never get that covered. I will sometimes do this in combination with the biologic. I also thought baseline there are 58 patients. We 12, there are still 52 in there. That's not that bad of a drop-out rate for something that does have GI issues. I thought it was interesting. I like having it in the toolbox. Yep. I love having Riflumalast. I think we talked about it. For me, it is the new Methatrexate. We use Methatrexate for a bunch of stuff. It's a safe medication. I don't want to overblow the side effects of Methatrexate. But you do have to do monitoring and you have to go through all those potential side effects. Riflumalast is just, I love it. It's my Methatrexate. There's beta that it reduces cardiovascular morbidity and mortality in COPD patients. I don't know if I've mentioned this before, but there's one study where they gave it to young healthy people and it made it smarter. If you were smart enough, you would remember that you told us that. Clearly, you're not taking enough. I need to have my dose. It might help me. I have a friend who is on it. He had this crazy gingival plasma cytosis. Friable red gums bleeding anytime you ate anything. Trouble brushing his teeth because it was so bad. I was like, "Oh, I've got to get gingival hyperplasia. He went to see a good oral pathologist. The oral plasma cytosis," which he's like, "I've seen six cases ever. This is incredibly rare. I wish I could put them on a test like I think it would work." I was like, "Oh, but I can't get a cover." I was like, "Oh, try the Riflumalast. Worked amazingly, amazingly." He's a healthy, 53-year-old guy. He lost 40 pounds because it was just the GI, the nausea, the effects on the bathroom, the whole thing. It was miserable. It was interesting having a friend on it rather than a patient. I'm hearing what he had to say. Well, I want to thank everybody for joining us this week. Hopefully you found the articles in our six-pack interesting and that you will find them useful in your day-to-day practice. If you've got questions, if you've got comments, ideas for topics, we should cover on the show. Shoot us an email at
[email protected]. Again, that's
[email protected]. I do really want to recommend if you haven't been there. Go check out the scholars and medicine platform. If you just Google scholars and medicine, you will find it. They've got 80 hours of really well-done Derm lectures, a lot of content across the board in terms of meetings, abstracts, new stuff out of the journals. Just a fantastic educational platform that is at no cost to us as Derms, especially sending medical students, people new to Derm. MAs, people who, like I said, knew into Derm just great platform. But all right, I hope you learned a few things. I hope you laughed once or twice. And mostly, I hope you plan and enjoy this next week. Until then, I'm Matt Cyrus. I'm Tim Patton. I'm Laura Ferris and we are Dermsundrugs.
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