Melasma, and Vitiligo, and Warts, Oh My!

Welcome to season two of Derms on drugs, a video podcast brought to you by scholars and medicine, the best educational platform in dermatology and provided no cost medical providers. Derms on drugs is we're cutting it sure meets it or miscommunity. I'm Matt Syres from Dr. Botology in each week and joined by my residency buddies Dr. Laura Ferris from the University of North Carolina, Dr. Tim Patton from the University of Pittsburgh and we use our 60 years to combine derming experience to discuss debate and dissect the hottest topics in dermatology. It is everything you need to know to be in the Cain Gids at Derm and you'll hopefully have some fun listening. New episodes drop every Friday on scholarship medicine, Apple Podcasts, Spotify and other major podcast platforms that a reminder that there is a video component that has the key figures and tables from the articles we talk about. This week we've got another one of our patented six pack episodes where we are going to go over what are the coolest things we've seen in the literature recently. Let's go ahead to Dr. Ferris to kick it off. All right. So I am doing a review paper out of the job. So I know we like to do studies but I thought this was interesting. It was a review, you at all Sherry Lippner, Lotus now trek zone for treatment of dermatologic conditions, a clinical review. Because I feel like you always see like, oh, maybe now trek zone. Maybe it works for this. Maybe it works to that. So I thought it would be good to just go over like what did they have? So I want to post from there there's a table that summarizes everything that I think is like just a great reference to have. Before you start, have you ever ever prescribed Lotus now trek zone? Yes. Yeah. So I've prescribed it twice. Both times the patients had such crazy dreams that they literally stopped the now trek zone because of the dreams. Yes. That was bizarre. Bizarre, bizarre, vivid dreams is the like the number one side effect of low dose now trek zone. They get to tell patients that that might happen. I mean, I don't know if anybody's ever died of a vivid dream, but you know, scary dreams are scary. So it makes you are they are they usually bad dreams or can it be like, is it just normal dreams are going to be vivid? I don't know. We'll put you on some and you can let it know. Right. I think what you need, you need some low dose now trek zone in your life. I'm a try. I may try it. It's tough on a dichofoam once just to see and then try drinking on it. And yes, I got hives in a cough. So maybe I'll try the now trek zone and then I'll report back. Sounds good. All right. All right. Let's go. What what do we mean by net low dose now trek zone is basically one to six milligrams per day or per night, which is usually what's recommended. So a couple of things that I learned here. So now trek zone is just an opioid receptor blocker. So if you use it the full dose by 50 to 100 milligrams, it's really a continuous mu receptor blocker. However, at low doses, the block what you get is sort of brief, you know, on and off, like brief blockade. And so that paradoxically up regulates the endogenous opioids. So endorphins and caffalins and it increases mu capa and delta and opioid growth factor receptor expression. So that really shifts it more from being a capa to a, which like shifts you from a capa to a mu profile. And so this is good for itch and neurogenic inflammation and also may enhance care, tennis site migration. It also blocks to like receptor four. I did not know that. So you get sort of blocking a pro inflammatory cytokines like I'll one I'll six TNF. Okay. So where does it is totally receptor four, the one that in myquamad activates. Yes. So it's like the anti-emaquamad. Okay. All right. Fair. Okay. So where does it work? It seems like kind of some of the best data or are seemed and I mean, I use the term best data very loosely, Haley Haley disease. Okay. So different case series like retrospective study sort of in the three to four and a half milligram a day. There's some, you know, 30 to 100 percent clearance are and reduce parietus pain and flare frequency about an eight patient one study, eight patients, 77 percent improvement in body surface area. Another study showed really minimal. So I think it's time to consider adding. Now they're like, you know, where it really works well as if you added to do pixel, but I, you know, we recently looked at a do pixel and Haley Haley disease study that showed like do pixels pretty effective. So it may have been more than do pixel, but I think something to think about, dear A's disease sort of similar data that low dose now checks on. So they get something to consider. There is some data for just, you know, parietic primarily, parietic diseases. So epidermalysis below, so perigenosa, three milligrams a day of mal, of now checks on plus, clobate is all improve symptoms, systemic sclerosis, four and a half milligrams per day for two months, reduce parietic and three out of three patients. So you know, something to think about some of those conditions where patients are really itchy. After dose 50 milligrams daily can improve itch and patients in some studies too. So just think about that like in planis and scarring alopecia. So there was some studies that showed reduction in basically like FFA like in planopilaris at with three milligram dosing. So, so that was good. Now when you really got into the like randomized clinical trial, there was one of three milligrams of low dose now checks on plus clobate is all versus placebo alone. I'm sorry versus placebo plus clobate is also everybody got clobate is all. It's did you get now checks on or placebo and there really wasn't a difference for LPP like in planopilaris. So it was really more the clobate is all doing it. There was nail like in planis. They did show some improvement that some nice clinical pictures. So maybe nail like in planis is a place they did three milligrams a day of place to consider it. There is some data in psoriasis but the mean Pazidrop was like 18 to 13. So maybe something to consider obviously that's not our main you know, not the main thing that we would do. A few case reports on dermatomyositis Hs and also like body focused repetitive behaviors. So excoration on a chafasia, tricotelomania. So the theory behind that is that you sort of disrupt the mesolimbic reward system. And so you modulate that. So I think that that is something that is potentially you know, something to consider adding for some of those. When people have those repetitive skin picking, it's really hard to know what to do with them. What is just practical? Think about one to five milligrams once a day. You can start at low like a milligram a day and then titrate up by a milligram every one to two weeks. They most common A.E. Vivid dreams. Insomnia had a dry mouth vertigo. You do not need to do lab monitoring. Who should not get this? People who are on opioids. You're going to sort of negate that. You don't use it with people who are in people in liver failure. And also you do have to compound this to get one to five milligram capsules. That can be 35 to 50 bucks a month. So that can be expensive. However, there is a dark Elston hack, which is take five 50 milligram tablets, crush them up, put them into eight ounces of pure orange juice. And then that makes a one-meg per mil suspension that is stable for up to two months. And that's about $2.50 a month. So something to think about using. And I would say, look, if you want to use it, look at the nice table that is in this paper because it does a good job of sort of showing you what are the studies, how many patients, what was the dose, what was the result? Wait, fair. So I've got this. Was that was that a supplement? Because I've got the the paper itself pulled up and it's got a good table on like, uh, add stuff you got to warn them about and contraindications. But I didn't there was no table in the one that I know you're right. It I think it will I think that the table was actually a why follow the supplement to get it. Because yes, I did because I was like, why do they not put this in the body of the paper? This was like the best thing in there, not the adverse events. So if we can actually link to that on our website, that would be great because if you just proves the paper, you're not, you're going to miss it. But it's actually like the best part of the paper I thought. Yep. Okay. The I was I'm glad you brought up the Durk Elston thing. I was going to I remember that when it came out, I love that kind of stuff of like, crush it up and put it in whatever. Uh, so yeah, I thought I thought that was good. How much of either like I like is that I've prescribed it twice. I wasn't convinced it did anything the two times I prescribed it. Do either of you use it much? Much no. I think I've used it in Haley Haley. It was like, man, is it working? That's a disease where it's like you think something's working and then they flare and you know, so that's probably where I've used it most. I've maybe used it in like, um, pride. just like, you know, senile prayer or not, we shouldn't call senile prayers. What are we called? - Prayer. - Prayeritis among old people. - Crazy paritis. - There's the prayeritis. - And what? - Crazy person paritis is what we call. (laughing) Okay. So-- - I don't call them. - No, so right, I think like Dr. Ferris said, like just hard to treat things where you're like, you know, maybe you're a little better on this, maybe on that, I have something else to throw at you. - Right, I'm not blown away, but every once in a while, you know, you get a patient that comes back and it's like, you know, the plebades all works really well for flares. I do think that being on the low dose now, Trekzone has helped with those flares overall. Can you refill that? And you're like, yeah, okay. - Yeah, I think I would try it now for now. Like in plan as seeing, if you look at that paper, they've got some nice pictures. So, you know, I think that's a tough condition to treat unless you wanna go to like systemic, you know, not the trexator, acetate, and things like that, Jack and I better. So, maybe we're trying for that. - You did mention using it for like skin, picking disorders and that kind of stuff. That actually reminded me the, so my psych person had me start taking an acetylcystine. And he said, there's actually good data. Like it's a normal recommendation now, an acetylcystine for OCD, and he sees good efficacy and anxiety, you know, it's been published for skin picking disorder as well. And they have sort of figured out that it's not through its antioxidant effects. It's that it helps with glutamate processing in your brain. And so, the other thing, there's some data that an acetylcystine is hepatoprotective in heavy drinkers and may reduce the severity of hangovers if you take it before you drink by replenishing liver, whatever the sit, whatever the thing is that's the potent antioxidant that gets used up, which I'm blanking on at the moment. - That's interesting. Yeah, I do, I do for people who have a lot of skin picking, I do an acetylcystine a lot too, but it's sort of another thing to consider adding. All right, Patent, let's go on what he got. - All right, my first six-packed paper from November 2025, British Journal of Dermatology, titled "Metformin in Junction with Doxycycline is not superior to Doxycycline monotherapy." For hydride anditis, subvertiva, results of a phase three double-blind randomized placebo controlled trial. It was a research letter, first author, PIM Arts from the Netherlands, a Dutch study that always makes me think of that line from Austin Powers. There are only two things I can't stand in this world, people who are intolerant of other people's cultures and the Dutch. Always makes me laugh. We covered a trynetics study on an earlier episode showed that these crazy reductions in things like cardiovascular disease, cerebral infarction, death, et cetera, and H.S. patients that were treated with either an SGL T2 inhibitor and/or metformin. You guys remember that? I mean, it was like crazy numbers, like decrease in death of like 75% or something like that. Although, how do you decrease death? Everyone's gonna die. But I think it was probably during the time period of the study. And yes, the delay death. Yes, right. And so I was talking to another dermatologist after that episode aired and they were like, so are you gonna prescribe metformin to all your H.S. patients? 'Cause I don't really think it works that well in the treatment of H.S. And I was like, you actually listen to the podcast. So is metformin an effective treatment for H.S. The authors performed a double-blind randomized placebo control trial patients either received doxycycline 100 milligrams daily or in placebo, or they took doxy 100 milligrams a day, plus metformin, uptight traded from 500 milligrams daily to 1500 milligrams daily. 62 patients randomized, five patients discontinued the study. So final numbers, 29 patients in the doxy metformin group, 28 in the doxy-only group. Both groups showed statistically significant improvements compared to baseline. But there was no statistically significant differences between the groups and change of IHS-4, the IHS-455, high score 50 change in players, and count, DLQI and pain. So it didn't seem that metformin did much to help any of those sort of H.S. measures that are commonly used in studies. And the group taking metformin, metformin did what metformin does. There were decreases in BMI, laser-coferenced glucose levels. That's good. It was a six-month study. Maybe there would be more statistically significant differences that the study was carried out a bit longer. So the conclusion the authors, that they make seems reasonable to me. They said, quote, "Even though metformin therapy did not improve the clinical outcome, we still consider it in addition to H.S. treatment, armamentarium for the improvement of H.S. comorbidities." So am I gonna start it like in all my H.S. patients? I don't know. I don't think so. If patients' disease doesn't improve and maybe difficult to convince patients to remain on therapy, but if you can demonstrate objective improvements and other things like weight loss, glucose levels, waist or conference, maybe they would continue therapy. Like metformin was like kind of a poor man's, or like a poor person's, no need to be sexist. G-P-1 receptor agonist. I don't know, what do you guys think? - Yeah, I took it for a fairly long time, whenever it first came out that it might make you live longer, I did not lose any weight. - But you're still alive. - Yeah, he am still alive. But when I took a G-P-1, I did lose a lot of weight. So it, as most things that are a poor man's anything, it didn't work nearly as well as the rich man's version. - I love this podcast because like Matt has personal experience without 50% of the things that we talk about here. - It literally is a derm on drugs. It should just be derm on drugs. - One derm with two of his friends. - Yeah, I said. - What was I gonna say? My experience has been what, like the colleague that talked to me after the show. I mean, I met Foreman, it is not something where I think like, oh my gosh, this is gonna make your HS so much better. So I would say I don't prescribe it like very often at all. - I do a little bit for HS when I need like an adjunct therapy. And when like they need, they clearly would benefit from that form and from sort of a systemic disease. - Like comorbidities. - Like comorbidities, yeah. I mean, I keep thinking about it now more like, should I be do, like, you know, we see a lot of patients with CCCA, like should I be putting those patients on it after our podcast with Crystal and that great discussion that we had. But, you know, sometimes they're harder to say, you kind of need some met Foreman 'cause you're hemoglobin A once he's like nine anyway. So what's the harm, you know? But. - All right, there. - All right, it's like a nice, really kind of design trial. Does it help clinically with HS? No. - Right. - I mean, I thought it was a, like the studies that need to be done. It's kind of nice that somebody actually took the time and effort, randomized double blind placebo controlled. You know, it's not setting the world on fire, but it's nice to have studies done like this. And now we have kind of more clear data to say, it's not gonna help or it's gonna help with this other thing, but not really the HS. And so good for the Dutch. - No, and it's good. Like they didn't, they did look at things, like did it change like the flares and all that stuff. But I guess, you know, if you think about metformin as being anti-fibrotic, if it maybe, you know, you could imagine that what it might really do is prevent the scarring. And HS and so does it prevent progression? You know, I think like one of the key questions is, how do you prevent progression from a early stage progression, right? Because once you get, like you never go backwards in early stage. So if you can prevent going forward, I would love to see that data. That's a really hard study to do. But that was my only thought looking at this. - Okay. All right, let's jump over to my two articles. Keep these very quick. One was looking at a low salicylate diet in chronic urinary care. So interesting concept behind this. So we know that there's a significant number of people with chronic urinary care, who are made worse by salicylids, whether that's aspirin or NSAIDs or anything else. So these people said, well, and this was a title of the study, effective low salicylate diet and blood salicylate level on the symptom control of chronic spontaneous urinary care. As was done out of Korea, it was open label trials. So you know, cause it's really hard to do any kind of a, you know, double blind trial whenever you're talking about a dietary intervention. So that people follow a low salicylate diet for four weeks. They measured their blood salicylate levels before and after and they looked at their or the carriers scores. And the main takeaway was it made a difference. Their quality of life improved the measure that they use that improved by about 30%. The UAS 4, which is different, same idea as the UAS 7, UAS 7, you do seven days, UAS 4, you do four days. it in the end. decreased almost by half. So now this could all be placebo effect, right? That's one of the problems whenever you do a dietary intervention, you don't know is it just because people think they should get better. It did reduce their blood cellulite levels. So whatever they want on the diet. So the main takeaway here is this is another example of if you've got a patient with chronic or a caria who really is like pushing on, "What diet, diet? Should I go get allergy tested? Should I do this? Should I do that?" Your answer can be, "Well, we know that you're not allergic to any foods that doesn't show up as hives, but certain foods can make your mast cells, which are the cause of a caria, more sensitive." And so if you really want to try a diet, go online and look up a low-solicilite diet. And it's interesting stuff that's what's in the low-solicilite diet. So they will post a link to one in here, but it's there are certain nuts and seeds, like almonds are very high in silicilits. Whenever you talk about vegetables, endive and gercune, peppers, tomatoes, right? So tomatoes are very high in silicilits, so maybe that's why so many people say tomatoes make them worse, dried fruits, apricots, avocados, right? So normal foods. So just interesting. Do I think it's, you know, is it going to let me use this instead of Dupy or, you know, Rapsido? No. But I might use it in conjunction with them. Kind of my main takeaway. Any thoughts from either of you? Wasn't there, wasn't there something about if the patients were on something like four times dose anti-histamine or omolysmab and not getting better on that at all, that the silicilite level actually didn't change? Whereas if they got a little bit of a response, that's where you saw a drop in blood silicilates. And so kind of implying that like for the people to have no response, whatsoever to standard care, therapy, maybe it's not going to help them. Yes. But if they get a little bit better and are just kind of looking, what else can I add, maybe that's where you push it more. I don't know. I thought that was a weird. Yeah. And I think what I mainly took from that was the idea that like if you have horrible urticaria, this is not really going to help. But if you're like borderline, oh, your disease is almost getting better, it might tip you over the edge. Yeah. It was also a good reminder to me that when you have a patient who comes in with urticaria, make sure that they're not on aspirin, right? We know aspirin makes it worse. And sometimes I just forget to like go through their med list or it doesn't always show up on med list. Ask them if they're on aspirin. I've had a couple times where I've gone people that are simply by having them stop their aspirin. So okay. You know what, that's again something that I forget to do. I will outright say I forget to ask people. So yeah, thank you, Ferris. Okay. AI is going to take your job. AI will never never forget. Never forget. Never forget. That's right. It's true. The other article, this was just a, again, nice thing. So hyperthermia. So like putting a heating pad over warts or meliscoem, Ted Rosen has talked about this a little bit. It does work, but this was a study that looked at hyperthermia combined with hydrogen peroxide. And so it wasn't like the expensive, you know, 35% hydrogen peroxide that whatever the hell that stuff was that they came out with for SKs that nobody used. It was like, so they did hyperthermia, they would do it three. So just basically a heating pad set on high. So 44 degrees Celsius, which I can never remember what that is in Fahrenheit. It's somewhere around 120 degrees, I think, 100, around 110, 120 degrees. They did daily wet dressings, either normal saline or hydrogen peroxide and just normal 3% hydrogen peroxide for six weeks. And then the warp would get hyperthermia four days, one days, one 30 minutes each session, one session a day, for days one through three, days nine through 10 and days 16 through 17. And the combination was a little bit better. So the hyperthermia cleared about a third of warts and the hyperthermia plus H202 cleared about 50% of warts. So am I going to use this probably not, but like anything that's about warts and is something non-invasive that you can like give parents to do so that they feel like they're doing something is worth thinking about. Wait, we take me through, I was trying to read it and then I got like, I don't know, I've distracted. Like how, how do you tell a patient to do this? You got a heating pad. It's on high. Each week you're going to do three days in a row of 30 minutes of the heating pad. Yes. Then what do you do with that hydrogen peroxide? So what I will be telling people to do is basically take a band aid and get it wet with hydrogen peroxide and put it on. And it's an interesting question of like, is that actually doing it? Because the hydrogen peroxide in within probably minutes is just water, right? So it is not like a stable molecule once you put it on the skin. So like I think part of it is just apparently having, keeping the work wet is maybe bad for, I don't know, but it'll just be. But they did it with water and it didn't work as well. They did it with normal saline. It didn't work. Right. So the it's it's hard for me to understand why this worked. But you don't have to understand why. But how, like how would you practically have a patient replicate this? So I would just have them put enough drops of hydrogen peroxide on the pad of a band aid to get it like wet and then put that on, leave it on until it falls off. Put it on every day, leave it on until it falls off. That's. And then only three days a week do you do the heating pad? Three days in a row, heating pad on high 30 minutes. And then the other, but every day you put some hydrogen peroxide on a, on a, on a band aid on your ward. Yes. And I will be, I don't know, I don't know that they said this in the article, but I'll be telling them to put the band aid out like the days are going to heat put the band aid on and then right after you put the band aid on put the heat on to get the combined effect. But yeah, I don't know if that's, I don't think they said if they actually did it that way or not in the article, but that seems like it'll have more placebo effect. Would be my guess. All right, it's worth a try. It's worth a try. People need things that they can do at home, trying to like manage access in a big house system, like seeing people every month for warts doesn't seem like a good use of our resource. So if there is something that people can do at home that's cheap and safe, I like it. There was a discussion this week on board certified dermatology group about giving, using a disposable cure at to pair plant our warts and then giving the person the cure at to take home and let them continue to pair their own wart, you know, a couple of times a week. And people have said that that works great in their experience. Like either I'm like if you about giving somebody a sharp object to take home, but I'm pretty sure they can buy those themselves on Amazon. Yeah, that's okay. Right. So they probably all of knives at their house. So yeah, okay, fair. I'm not allowed to have them in my house, but I forget that's different. That's a whole different thing. It turns out you can buy curets on Amazon. Okay, fair. So you don't even have to give them to them. Okay, you can just tell them to go buy an Amazon. All right, exactly. Let's move on, Patent. Or I'm sorry, fairs, we're back to you. What do you got? You are back to me. Okay. So I decided to take on the knockout study. A randomised phase two clinical trial to treat moderate to severe plaque psoriasis patients with high induction dosing of risen kissy map. This is Andy Blowbelts. He's I've seen him present it. I think he's very excited about this. So this question is what happens if you hit hard with high dose sky-rizzy up front then stop? Can you knock out the T cells? And I feel like it's kind of interesting because I've liked to pay for some of them presented like, oh, yeah, I mean, that's like the way we can do this. But then you read it. You're like, did that really work? But okay. So what they did, single center randomised double blind study. It's a 100 week study, 20 adults, 10 in each arm. They either got sky-rizzy at double dose or four full dose. So 300 or 600 milligrams as their dose instead of, you know, the FDA approved 150 milligrams. So they got it at weeks, 0, 4 and 16. And then they got no more drugs. So their primary endpoint was not actually Pazzy score, but it was the change in epidermal resident tissue resident memory T cells. And I will not go into all the science because I'm not, I don't know enough of it to be able to explain it well. And I don't think it's what's going to be of interest. They also looked at like safety and Pazzy 100. Okay. So what did they find? So by weeks 16 after two doses, 100% of patients had a Pazzy 75 response, 94% Pazzy 90, 66% Pazzy 100. And at the week 28, those responses were like same 94% Pazzy 75, 94% Pazzy 93% Pazzy 100. nearly 90% had a deal QI-01 of zero-01, suggesting basically no impact on quality of life. Now interestingly, the 300 milligram group did better than the 600 milligram group. Then they looked at week 28 to 100, no further dosing. A bunch of people did drop out to pursue other therapies, which would tell you that this wasn't like it didn't truly knock out their psoriasis. But at week 52, so a year in 36 weeks after the last injection, 78% still at a PASI-75 and 44% still had a PASI-100. By week 102 of the six patients who like stayed in the study and made it that far, which was 11% of all the people who started the study still had a PASI-100. The mean improvement at week 100, so two years in was about 63% in their PASI score. Now still, there was not like a big separation between 300 and 600. Now they're like, "Well, the 600 milligram are actually at worst disease and more severe and have been longer standing, so maybe they were a harder to treat." So, this is sort of in the IBD realm anyway. So, nothing that was like crazy. What happens to resident memory T cells? I am not going to like go crazy on all these plots and all this stuff. But basically, they did see a reduction of T resident memory cells in the skin and that was actually higher with the 600 milligram dose. So, if you had a mean 22 cells per sample at baseline, they dropped down to three cells per sample in the high dose group. They also talked about the different subtypes. So they had this T resident memory type 17, so there's the IL-17 producing ones and the T resident memory type one which are like interferon gamma ones, expressing cells. And so they actually showed a reduction in both of the cell types. So, how do we think about this? What are T resident memory cells doing? You ever notice you treat a patient with psoriasis? They get better, they're doing great. When it recurs, it almost always comes back and exactly the same plaques. And we think that's because T resident memory cells live in the skin and they're sitting there waiting to repopulate the skin. So the idea was what if it's like your local memory hard drive sitting in the skin, can you knock that out by just getting rid of as much IL-23 as possible? And the idea of it makes sense because we do know that IL-23 reduces T resident memory cells. Like, Kiselke-Mab studies, interestingly IL-17A blockers which are super effective in psoriasis, they do not deplete T resident memory cells. So I thought this was an interesting study. From a clinical perspective, it did not knock out the disease. But it was safe and you did get a better response than what you saw with like, you know, with the phase three studies with, you know, standard dosing skyrizzy. Do I think that this is going to be like the holy grail we're going to start doing this catch people early and we're going to knock out their psoriasis? I do not think that that is going to be the case. But it's interesting and maybe an IL-23 inhibitor combined with another drug that maybe will knock out the resident memory T cells may be the way to get longer lasting responses. I don't know. What did you guys think about this? Have you been hearing about the knockout study? Yeah. Pat, now let you go first. I thought the same thing. I'm reading the paper. It was like, is this how I'm going to start prescribing it? And I was like, probably not, but maybe I was missing something. And what was best, like, I've been hearing people talk about this for a long time and I was expecting it to work. But based on the way I heard people talk about it, I was like, oh, this is it. This is going to be like, you get it merly, you blast them with huge doses of skyreasy and we can cure their psoriasis. And this did not show that at all. Two people were cured at two years. One of them, they're like, oh, they were really, they're thin and they had, were like, had only had psoriasis for like less than a year. And that maybe that's it. But then the other person was like obese and had had psoriasis for a long time. So I'm like, all right, that wasn't the difference. So yeah. So it's been out there for a long time. Go ahead. Yeah, it kind of fed off the idea of the IL-23 super responders, which I think has been around for a long time. And if you're a super responder, then a higher dose, you're like a super duper responder. And it kind of seemed along that same sort of. In my reading of it, I did not see that there was some correlation. Like the people who did really well wiped out all their resident memory T cells or like that there was, and again, it's a small study and it's very intensive to try to do all these. And really it was at 52 weeks that they looked at everything. They didn't look at it. They didn't do the biopsies at 100 weeks. So, you know, I didn't get like the, the satisfying answer. I wanted like this is how we're going to do it. But I do think that the idea of maybe IL-23, which is important for resident memory T cells combined with something else might be the way. Maybe you can clear people, then do something to their skin to those areas to try to clear it. I don't know what that is, but. Patten, what do you got? My second six pack, September 2025 Journal of Cosmetic Dermatology, randomized clinical trial on the efficacy of oral tranacsemic acid versus topical tranacsemic acid in treatment of melasma, it was by Hadari at all. This was a single center randomized trial conducted in Iran, or as Zaire likes to say, Iran, quick review. How does an antifriberinolytic agent even work to treat melasma? UV increases keratinocyte production of plasma. Plasma releases arachidonic acid, leads to prostaglandin production. And apparently prostaglandin production can stimulate melanocytes. Plasma can also apparently increase melanocytes stimulating hormone activity. And TXA blocks the transformation of plasma's midagent to plasma. And so it inhibits all those effects. This paper also states that TXA may inhibit tyrosinase activity because of its structural similarity to tyrosine. Maybe? I don't know. What we do know is that oral tranacsemic acid is very, very effective for melasma. I've never personally used it because I scared the bejeebus out of patients by telling them that the drug is used to clot blood. Perhaps I need a more elegant and sophisticated approach to these patients, but anyone who knows me, I am neither elegant nor sophisticated. So the struggle is real, yo, I do use topical TXA all the time. You can get this through compounding pharmacies, pharmacy at eye use compounds it in 3% and 5% formulations. Back to the study, 25 patients were given oral TXA 250 milligrams daily. 25 patients were given topical 5% TXA to apply twice daily. The results, it was kind of confusing and there's like some flat out errors. The endpoint was the reduction in the Mazee score at week 12. That's MASI, but the manuscript goes back and forth between MASI and MACI. They do it like a couple of times. Massey is a pretty standard melasma scoring thingy. They report that the percentage reduction of MASI was greater in the oral TXA group, but it wasn't. I mean, if you look at that graph, the oral TXA group went from a Mazee score of 6.8, 3 to 4.02. And the topical group went from 7. So it was almost 8 to 4. So again, systemic TXA 6.8, 3 to 4, topical group 8 to 4. The topical group did better. So where they got the numbers is that 4.02, which was the N Mazee score, that's 58% of the starting Mazee score, but that's not a reduction. And the 4.04 is 50% of 7.94, but those are not percent reductions. It was like TXA, you were at 50%, no, 58% of the starting Mazee. And when you did topical TXA, you were at 50% of the starting Mazee. So if you actually do percent reductions, it was 41% reduction in the oral group and 49% reduction in the topical. So some errors on reporting of the data, it's hard to believe that the topical was better than the oral form. Even if it may have not been statistically significant, I don't know. I still prescribe a magic mix of TXA, nice, cinema, and cogic acid, and probably continue to do so. But a couple things were off in the paper, so I don't know if I'm going to be telling patients to like, hey, they did the study and the topical was definitely better than the oral form because, yeah, the data was just incorrect the way they reported it. So do you, so you exclusively - Like do you more or less only use the topic a little at this point? The magic mix? - I'd never use systemic. I'm telling you, I brought it up, but I'm like, it's really, really good. And they're like, okay, side effects. I'm like, you die of a blood clot. - Yeah. - How well does the compounded stuff work? - Patients often ask for refills of it. They're like, I like that stuff. It seems to be working. Well, I'm not doing like official studies. It's one of those drugs where, you know, what you're doing skin checks on a regular basis. And they're like, oh, hey, you remember that stuff? Few parts of the crab. Can I get more of that? I really like it. It really did help kind of lighten my skin. I mean, it's got other things in it, right? Nice, cinema, nice anti-oxidant. Should be part of everybody's skin care regimen if you actually believe in that crap. Trent Noan, never bad, right? - Yeah. - Code, Kojik acid. - That's a legit tyrosanase inhibitor. Right? I mean, what's-- - It sounded funny. I almost did this paper, but I didn't. That was recently published in the scientific reports or whatever. And it was a randomized controlled trial of trannixemic acid with niacinamide versus hydroquinone, formalasma. So they actually, and they were like looking at some niosomal, like some formulation. And that didn't matter. But the take home point was trannixemic acid versus hydroquinone, similar efficacy, fewer side effects with the trannixemic acid. So I thought that was actually pretty good. Maybe I should have done that paper after all. - Yeah. So compare-- and this was hydroquinone, 4% cream. - Okay. - But yeah. - I think the biggest takeaway with melasma for me remains whatever we're doing. We need to have them use iron oxide containing sunscreens. That that is the sunscreens. The tinted sunscreens with iron oxide seems to make a huge difference with whatever-- whatever the heck else we're doing. That's the crucial thing. - Yeah. And make it topical trannixemic acid. - Yep. That's-- I'm switching over. I've done just-- the oral, I've never prescribed this topical. I'm going over to the topical now. You got-- - There was one patient in the topical that dropped out because of irritation. So that you-- and there were zero patients that dropped out because of side effects in the oral group. Even though there was like, I think 14% reported oligomeria, there was all females in the study. I can't imagine women having a problem with oligomeria, but maybe I am wrong about that. - So that was only in the oral group who got the oligomeria? - Yeah. - Okay, maintenance. Okay. Huh. 'Cause that's what-- Like it's-- I mean, it sounds a little bit weird, but it's got to come out some-- Like, it's-- Yeah, I'm confused about that. It says, I don't know what you make of that. - Yeah, well, 12 weeks study, I mean, short period of time, but-- - Okay, all right, all right. I'm gonna jump over to my last two. First one, just confirm something that you would have believed to be the case anyways. So randomized double blind treatment would draw or continuation with reccellinative cream and beta-ligo findings from the true V long term extension phase three study. So basically, right as you would expect here, what they did was once-- If people got better, they got randomized to either stop the-- Go on placebo cream instead of the absolute-- continuing the absolura, or to continue the absolura. And pretty much the main takeaway here. So reasonably big study, not huge, like 50 some patients in each group. And if you stopped it, the capillomire probability of maintaining Vassie 90, so your face got really, really better facial Vassie 90, your probability of maintaining it was only 24%. If you continued it, then your probability of maintaining it for a year via capillomire was about 75%. So as you would expect, the main takeaway is, if you give somebody absolura for facial beta-ligo and it gets better once they're better and they say, well, should I-- do I need to say, yes, you need to stay on it? Which is what you would have expected to be the case anyways. So that's just-- OK, that's what we thought anyways. The other one that I wanted to do that I thought was a lot more interesting was looking at long term follow-ups with penurises like anoidies. So this one was titled penurises like anoidies in University Department, Long term follow-up study. So this was done in Serbia and they looked for-- at long term follow-up, so penurises like anoidies patient, so $175, 135 kids. And they had long term follow-up in this. The median follow-up was like 10 years, 9.9 years. So a couple of things were interesting. So we're often told, or at least I was taught in residency, because this isn't like a disease that you see so much that I have like a good sense of like, oh, here's what happens long term. But in residency, I was pretty much taught that PLC can last a really long time and Plyva goes away pretty quickly. And that isn't exactly what it showed. So when you look at the-- and also that Plyva is more common in kids and PLC happens in sort of adults and elderly people. Again, not really what was seen. So when we look at PLC and Plyva, so there were 148 people with PLC, 43 with Plyva, and then 45 with mixed penurises like anoidies which kind of look like it could be either one. It was roughly a 50-- so Plyla was roughly 50/50 kids and adults. Plyva was roughly 50/50 kids and adults. The mixed was a little more kids, so it was more like two thirds kids in the mixed, one third adults. But the febro-osuertive mocha-haberman disease, like the horrendous Plypepinurisus-like anoidies, that was pretty much-- that was 85%. There were only like six cases of it. But five of them were kids and one was an adult. So the febro-osuertive version does seem to be more common in kids. But then the second thing-- duration of disease. So PLC, the median duration of disease was four and a half months, four months in kids, five months in adults. For Plyva, the median duration of disease was three months. So shorter-- so three months as opposed to 4.5, 3.2 months in kids, two months in adults. And so initially I looked at that and was like, oh, wow, they're about the same. But the range was very different. So PLC, the median-- the range of duration was zero months to 144 months or 12 years. In kids, it was zero months to 66 months. And in adults, it was zero months to 144 months. Whereas Plyva, the range was zero to 36 months. So-- and in kids, that was zero to 36 months. The range of adults was zero to 10. So I guess I would say that the longest Plyva went in anybody was three years, whereas PLC lasted up to 12 years. So even though the median's were about the same-- or not about the same-- but not that different-- three months versus four and a half, PLC does have more probability of lasting forever. The-- or not forever, but for all these are really, really long time. And then the fibroocerative actually lasted longer than I was expecting. So I expected that to be one that was like, happens in as horrible and it goes away quickly. No, that one, the median duration was five and a half months. And the spectrum, the range, was one to eight. So interesting, it sort of changed a little bit what I think about the difference between Plyva and PLC. So that was-- OK, great. The interesting thing to me and they didn't really talk about this was treatment. What do you do? So what do you guys do for Plyva and PLC patients? Pat-- I like math and track state. I've had patients. One of the last ones I had, I mean, I am catalog. I know we're always taught like, oh, that's such bad medicine. But like Q3 month, I am catalog 40, really kept turned or controls. So now I'm like, that's a very simple, safe thing to do. Phototherapy, you know, narrow band. And also those are kind of my go-to's. Yeah, math and track state, phototherapy. Maybe I am K. Pat, and what do you do? Isn't Doxie up there on Plyva? I think I've had patients where-- Yeah, sorry. Doxie, I do initially. I'm thinking more like long term. Yeah. And yeah, yeah, long term. Yeah. But I think Doxie up front, I've used a fair amount and have had decent responses with that. And I think in kids, we're supposed to use-- it's one of those deals where in kids, we're supposed to-- I'm supposed to use a Rithramisin, right? - Oh, yeah. - I think I remember that that I haven't treated kids in a long time, but I think I remember-- - Me neither. - You're like your first line as you try either a tetracycline or a Rithramisin, and then long term, yeah. I've treated a lot more PLC than I have believe of, like a lot more. So Bethatrix 8, low dose agree that's usually my go-to and then phototherapy if they can do it. But did you guys have the same like going into it? - I was surprised that the PLC, that the median duration was only four and a half months. I might-- - I'm surprised by that too. But it's-- - Yeah, it's not. - And like, patients always say like, how long is this gonna last, right? And like, you wanna have numbers. I don't think I'll give them four months. I'm gonna give them like two years. - Well, I'm gonna give them really variable. You know, in some studies, there have been people who've lasted over 10 years, but most people it's a lot shorter than that. It might be a couple years. That'll probably be my spiel. Plea while still, you know, I think I've seen three cases of Plea and my entire career that I was like, sure it was Plea, so that one I'll still be telling people, oh, generally goes away in like six months. But yeah, and there was just a study. I think we may have talked about it that a prema last works well for penurizes like an oedispectrum disease. So that brings up our favorite drug. Reflumalast may now be my first slide instead of methotrexate for all forms of penurisus like an oedis disease. All right. We will end it there. I wanna thank everybody for joining us today. Hope you laughed a few times. Hope you learned a thing or two, but mostly, hope in your plan 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.