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- [00:02]
A
Welcome to season two of Derms on Drugs, a video podcast brought to you by Scholars in Medicine. The best educational platform in dermatology and provided a no cost to medical providers. Derms on Drugs is where cutting edge sure meets hit or miss comedy. I'm Matt Zyrus from Docs Dermatology and each week I'm joined by my residency buddies, Dr. Laura Farris from the University of North Carolina, Dr. Tim Patton from the University of Pittsburgh, and we use our 60 years of combined derma experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be in the Canadian derm and you hopefully have some fun listening. New episodes drop every Friday on Scholarship Medicine, Apple Podcast, Spotify and other major podcast platforms. And 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.
- [00:54]
B
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. Ju et al. Sherry Lipner. Low dose naltrexone for treatment of dermatologic conditions. A clinical review because I feel like you always see like, oh, maybe naltrexone, maybe it works for this, maybe it works for that. So I, I thought it would be good to just go over like, what did they have? Also I want to post from there. There's a table that summarizes everything that I think is like just a great reference to have.
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A
Okay, before you start, have either of you ever prescribed low dose naltrexone?
- [01:32]
B
Yes.
- [01:33]
A
Yeah, so I've prescribed it twice. Both times the patients had such crazy dreams that they literally stopped the naltrexone. Because of the dreams. Yes, that was, it was bizarre. Bizarre.
- [01:48]
B
Vivid dreams is the, like the number one side effect of low dose naltrexone. So they have 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 me.
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A
Are they, are they usually bad dreams or can it be like, is it just normal dreams are going to be vivid?
- [02:07]
B
I don't know. We'll put you on some and you can let us know.
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A
Right.
- [02:10]
B
I think what you need, you need some low dose Naltrexone in your life.
- [02:13]
C
I may do that.
- [02:14]
A
I may try it. I put myself on disulfiram once just to see and then try drinking on it. And yes, I got hives and a cough. So maybe I'll try the naltrexone and then I'll report back.
- [02:26]
B
Sounds good. All right.
- [02:27]
A
All right. All right, let's go.
- [02:28]
B
What, what do we mean by net low dose naltrexone? It's basically 1 to 6 milligrams per day or per night, which is usually what's recommended. So a couple things that I learned here. So naltrexone if we is an opioid receptor blocker. So if you use it the full dose, 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 upregulates the endogenous opioids. So endorphins and kathlens and it increases Mu kappa and delta and opioid growth factor receptor expression. So that really shifts it more from being a kappa to a like shifts you from a kappa to a Mu profile. And so this is good for itch and neurogenic inflammation and also may enhance keratinocyte migration. It also blocks to like receptor 4. I did not know that. So you get sort of blocking a pro inflammatory cytokines like IL1IL6TNF. Okay, so where does it is.
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A
Is TOL receptor 4 the one that imiquimod activates?
- [03:49]
B
Yes. So it's like the anti amiquimod.
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A
Okay, all right.
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B
Fair.
- [03:53]
C
Okay.
- [03:53]
B
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 studies sort of in the 3 to 4 and a half milligram a day there's some know 30 to 100% clearance are and reduce pritis pain and flare frequency about in 8 patient 1 study, 8 patients, 77% improvement in body surface area. Another study showed really minimal. So I think it's something to consider adding. Now they're like, you know where it really works well is if you add it to dupixent. But I you know we recently looked at a dupixent in Haley Haley disease study that showed like dupixent is pretty effective. So it may have been more the dupixent. But I think something to think About Darier's disease. Sort of similar data that low dose now checks on. So I think it's something to consider. There is some data for just you know, pruritic, primarily paramedic pruritic diseases. So epidermolysis bullosa priginosa, three milligrams a day of, of naltrexone plus clobatazole. Improved symptoms, systemic sclerosis and a half milligrams per day for two months. Reduced pruritus in three out of three patients. So you know, something to think about some of those conditions where patients are really itchy. Standard dose 50mg daily can improve itch in patients in some studies too. So just think about that. Lichen planus and scarring alopecia. So there was some studies that showed reduction in basically like FFA, like in Plano Plaris at with 3 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 naltrexone plus clobatazol versus placebo alone. I'm sorry versus placebo plus clobazole. So everybody got clobazol. It's did you get naltrexone or placebo? And there really wasn't a difference for LPP like implanto pilaris. So it was really more the clobatazole doing. There was nail like implantus. They did show some improvement. They had some nice clinical pictures. So maybe nail like implantus is a place. They did 3 milligrams a day. A place to consider it. There is some data in psoriasis but the mean Pazi drop 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 excoriation onyophagia, TR onania. So you know it. So the I, 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, you know, when people are have those repetitive skin picking, it's really hard to know what to do with them. So 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. The most common ae, vivid dreams, insomnia, headache, 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. Don't use it with people who have. 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 Dirk 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 mg 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?
- [08:38]
A
Wait, first. 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 stuff you gotta warn them about and contraindications. But I didn't. There was no table in the one that.
- [08:57]
B
I know, you're right. It. I think it. Well, I think that the table was actually. I followed the supplement to get it because. Yes, I did, because I was like, why did they not put this in the body of the paper? This was like the best thing in there, not the adverse event. So. Okay, if we can actually link to that on our website, that would be great because if you just peruse the paper, you're not. You're going to miss it. But it's actually like the best part of the paper, I thought.
- [09:20]
A
Yep. Okay. The. I was. I'm glad you brought up the Dirk Elston thing. I was gonna. I remember that when it came out. I love that kind of stuff of like crush it up and put it in whatever. So, yeah, I thought. I thought that was good.
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B
How.
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A
How much of either of you like, I. Like I said, 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?
- [09:43]
B
Much? No, I think I've used it in Haley. Haley. It was like, meh. 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 pritus, like, you know, senile prayer. We shouldn't call it senile prioritis. Whatever we call it pruritus among old people.
- [10:09]
C
And what crazy person. Pruritus is what we call it.
- [10:14]
B
Okay, so I don't call it.
- [10:17]
C
No, I, So. Right. I, 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 and. Right. I'm not blown away, but every once in a while, you know, you get a patient that comes back and is like, you know, the, the betazole works really well for flares. I do think that being on the low dose naltrexone has helped with those flares overall. Can you refill that? And you're like, yeah, okay.
- [10:47]
B
Yeah, I think I would try it now for nail lichen. Plan is seeing if you look at that paper, they've got some nice pictures. So, you know, I think that's a tough, a tough condition to treat unless you want to go to like systemic, you know, methotrexate or acetran or things like that, JAK inhibitor. So maybe worth trying for that.
- [11:06]
A
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 N acetylcysteine and he said there's actually good data, like it's a normal recommendation now. N acetylcysteine 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 the. It's, 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 N acetylcysteine is hepatoprotective in heavy drinkers and may reduce the severity of hangovers if you take it before you drink by replenishing liver, whatever the sip, whatever the thing is, that's the potent antioxidant that gets used up, which I'm blanking on at the moment.
- [12:14]
B
Interesting. Yeah, I do, I do. For people who have a lot of skin picking, I do an acetylcysteine a lot too. But this is sort of another thing to consider adding.
- [12:25]
A
All right, Patton, let's go on. What do you got?
- [12:28]
C
All right. My first six pack paper from November 2025 British Journal of Dermatology titled Metformin in conjunction with doxycycline is not superior to doxycycline monotherapy for hydradinitis supper tiva results of a phase 3 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. Yeah, always makes me laugh. We covered a trinetic study on an earlier episode showed that these crazy reductions in things like cardiovascular disease, cerebral infarction, death, etc in HS patients that were treated with either an SGLT2 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 going to die. But I think I. It was probably during the time period.
- [13:29]
A
Of the study and yes, delay death.
- [13:32]
C
Yes. Right. And so I was talking to another dermatologist after that episode aired and they were like, so are you going to prescribe metformin to all your HS patients? Because I don't really think it works that well in the treatment of hs. And I was like, you actually listen to the podcast. So is metformin an effective treatment for hs? The author's preferred performed a double blind randomized placebo controlled 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. 5 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 in, you know, change of IHS4, the IHS4, 55 high score, 50 change in flares, an count, DLQI and pain. So it didn't seem that metformin did much to help any of those sort of HS measures that are commonly used in studies. And the group taking metformin Metformin did what metformin metformin does. There were decreases in bmi, waist circumference, glucose levels.
- [14:51]
B
That's good.
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C
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, 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 HS treatment armamentarium for the improvement of HS comorbidities. So am I going to start it like in all my HS patients? I don't know. I don't think so. If patient's disease doesn't improve, it may be difficult to convince patients to remain on therapy. But if you can demonstrate objective improvements and other things like weight loss, glucose levels, waist circumference, 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. GP1 receptor agonist. I don't know. What do you guys think?
- [15:45]
A
Yeah, it's, it's. I took it for a fairly long time whenever it first came out that I might make it live longer. I did not lose any weight.
- [15:55]
B
But you're still alive.
- [15:56]
A
Yeah, I am still alive and I, but I took a GLP one. I did lose a lot of weight. So it, it as most things that are a poor man's anything, it didn't work nearly as well as the rich man's version.
- [16:11]
B
I love this podcast because, like, Matt has personal experience. Without 50 of the things that we.
- [16:16]
C
Talk about here, it literally is a derm on drugs. It should just be derm on drugs with two of his friends.
- [16:25]
B
Yeah.
- [16:29]
C
What was I going to say? I, you know, my experience has been what? Like the colleague that talked to me after the show, I, I mean, I. Metformin. It is not something where I think like, oh my gosh, this is going to make your HS so much better. So I, I would say I don't prescribe it like very often at all.
- [16:47]
B
Yeah, I do a little bit for HS when I need like an adjunct to therapy and when like they need. They clearly would benefit from metformin from sort of a systemic disease 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, you know, podcast with Crystal and that great discussion that we had. But, you know, it. Sometimes they're harder to say, you kind of need some metformin because your hemoglobin A1C is like 9 anyway, so what's the harm? You know.
- [17:26]
C
But all right, it's nice like a Nice. Really kind of designed trial. Does it help clinically with hs? No.
- [17:37]
B
Right.
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C
I mean I thought it was, you know, these are 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, 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 just to say it's not going to help or it's going to help with this other thing, but not really the HS and so good for the Dutch.
- [18:03]
B
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 in hs. And so does it prevent progression? You know, I think like that one of the key questions is how do you prevent progression from. Of 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.
- [18:41]
A
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 urticaria. So interesting concept behind this. So we know that there's a significant number of people with chronic urticaria who are made worse by salicylates, whether that's aspirin or NSAIDs or anything else. So these people said, well, and this was titled the study effect of low Salicylate diet and blood Salicylate level on the symptom control of Chronic Spontaneous Urticaria. This was done out of Korea. It was open label trials because 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 urticaria scores. And the main takeaway was it, it made a difference. Their quality of life improved. The measure that they used, it improved by about 30% the UAS4, which is different. Same idea as the UAS7. UAS7, you do seven days. UAS4, you do four days. It increased, 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 salicylate levels. So whatever, they went on the diet. So the main takeaway here is this is another example of if you've got a patient with chronic urticaria who really is like pushing on, well, 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 urticaria, more sensitive. And so if you really want to try a diet, go online and look up a low salicylate diet. And you know, it's interesting stuff. That's what's in the low salicylate diet. So we'll post a link to one in here. But it's. There are certain nuts and seeds like almonds are very high in salicylates. Whenever you talk about vegetables, endive and gherkin peppers, tomatoes. Right. So tomatoes are very high in salicylates. So maybe that's why so many people say to tomatoes make them worse. Dried fruits, apricots, avocados. Right. So, so normal foods. So just interesting. Do I think it's, you know, is it going to use this instead of dupy or you know, rhapsody? No, but I might use it in conjunction with them. Kind of my main takeaway. Any, any thoughts from either of you?
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C
Wasn't there, wasn't there something about if the patients were on something like 4 times dose antihistamine or omalizumab and not getting better on that at all, that the, the salicylate level actually didn't change, whereas if they got a little bit of a response, that's where you saw a drop in blood salicylates. And so kind of implying that like for the papers they had no response whatsoever to standard urticaria therapy. Maybe it's not going to help them.
- [22:15]
A
Yes.
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C
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 there was a weird.
- [22:24]
A
Yeah. And it, it, 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 borderliney, oh, your disease is almost getting better, it Might tip you over the edge.
- [22:40]
C
Yeah.
- [22:41]
B
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 gotten people better simply by having them stop their aspirin. So.
- [23:03]
A
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.
- [23:15]
C
AI is going to take your job. AI will never forget.
- [23:18]
B
Never forget.
- [23:18]
A
Never forget. That's right. It's true. The other article, this was just, again, nice thing. So hyperthermia. So like putting a heating pad over warts or molluscum. 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, and 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 more 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 wart 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 day 16 through 17. And the combination was a little bit better. So the hyperthermia cleared about a third of warts and the hyperthermia plus H2O2 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.
- [25:00]
B
Wait, we take me through. I was trying to read it and then I got like, I don't know, 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 gonna do three days in a row. Of 30 minutes of the heating pad.
- [25:15]
A
Yes.
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B
Then what do you do with that hydrogen peroxide?
- [25:19]
A
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. Because the hydrogen peroxide in within probably minutes is just water. Right. So it. It is not like a stable molecule once you put it on the skin. So it, like. I think part of it is just apparently having. Keeping the wart wet is maybe bad for. I don't know, but it'll just.
- [25:49]
B
They did it with water and it didn't work as well. Or they did it with normal saline.
- [25:53]
A
It didn't work right. So the. It's. It's. It's hard for me to understand why this worked, but.
- [25:58]
B
Okay, you don't have to understand why. But how. Like, how would you practically have a patient replicate this?
- [26:04]
A
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 till it falls off.
- [26:15]
B
That's. And then only three days a week do you do the heating pad three.
- [26:18]
A
Days in a row, heating pad on high, 30 minutes.
- [26:22]
B
And then the other. But every day you put some hydrogen peroxide on a gauze or on a band aid on your ward.
- [26:29]
A
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 like the days are during the 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.
- [26:52]
B
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 health 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.
- [27:09]
A
There was a discussion this week on board certified dermatology group about giving a disposable curette to pair plantar warts and then giving the person the curette 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 if either. I don't know, I'm like, iffy about giving somebody a sharp object to take home.
- [27:35]
B
But I'm pretty sure they can buy those themselves on Amazon.
- [27:38]
A
Yeah, that's okay.
- [27:39]
B
Right? So. And they probably all have knives at their house, so.
- [27:42]
A
Yeah, okay, fair. I'm not allowed to have them in my house, but I forget.
- [27:49]
B
Yeah, that's different. That's a whole different thing. It turns out you can buy curettes on Amazon.
- [27:54]
A
Okay, okay, fair. So you don't even have to give them to them. Okay. You just tell them, go buy it on Amazon. All right, Exactly. Let's move on, Patton, or I'm sorry, Farris, we're back to you. What do you got?
- [28:04]
B
You are back to me. Okay, so I decided to take on the Knockout study, a randomized phase 2 clinical trial to treat moderate to severe plaque psoriasis patients with high induction dosing of risen Kizumab. This is Andy Blauvelt. He's. I've seen him presented. I think he's very excited about this. So this question is, what happens if you hit hard with high dose Skyrizi upfront, then stop, can you knock out the T cells? And I feel like it's kind of interesting because I feel like this paper's been 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 randomized double blind study. It's a 100 week study, 20 adults, 10 in each arm. They either got Skyrizia double dose or four fold dose. So 300 or 600 milligrams as their dose instead of, you know, the, 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 Pazi 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 pazi 100. Okay, so what did they find? So by week 16, after two doses, 100% of patients had a pasi 75 response, 94% pasi 90, 66% pasi 100 and at the week 28 those responses were like same. 94% pazi 75, 94% pasi 90, 83% pasi 100. Nearly 90% had a DLQ DLQI 01 of 0 and 1, suggesting basically, you know, 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 had a Pazi 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, the mean improvement at week 100, so two years in was about 63.3percent in their Pazi score. Now like still there was not like a big separation between 300 and 600. Now they're like, well, the 600 milligram arm actually had worse disease and you know, more severe and had been longer standing, so maybe they were harder to treat. Safety. Kind of interesting to say. What do we see about safety? There was really no new safety signal. 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 it, and that was, it was actually higher with the 600 milligram dose. So if they, if you had a mean 22 cells per at baseline, they dropped down to 3 cells per sample in the high dose group. They also talked about the different subtypes. So they had this T resident memory type 17s, those are the IL17 producing ones. And the inter and the T resident memory type 1, which are like interferon gamma ones expressing cells. And so they actually showed a reduction in both of the cell types. So, you know, how do we think about this? You know, what are T resident memory cells doing? You know, you ever notice you treated patients with psoriasis? They get better, they're doing great. When it recurs, it almost always comes back in 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, you know, to repopulate the skin. So the idea was, what if, like, it's like you're your local memory hard drive sitting in the skin. Can you knock that out by just getting rid of as much aisle 23 as possible? And the idea of it makes sense because we do know that IL23 reduces T resident memory cells. We know this from, like, selkimab studies. Interestingly, IL17a blockers, which are super effective in psoriasis, they do not deplete T resident memory cells. So, you know, 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, the phase three studies with, you know, standard dosing. Skyrizi, 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 IL23 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?
- [34:06]
A
And yeah, Pat, and I'll let you go first.
- [34:12]
C
I thought the same thing. I'm. I 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.
- [34:25]
A
And what was best. Like, I've been hearing people talk about this for a long time and I was expecting it to work, like, based on the way I'd heard people talk about it. I was like, oh, this is it. This is gonna be like, you get them early, you blast them with huge doses of Skyrizi and we can cure their psoriasis. And this did not show that at all.
- [34:47]
B
Two people were like cured at two years. One of them, they're like, oh, they were had really, they were 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.
- [35:03]
A
So, yeah, so, yeah, it's been out there for a long Time. Go ahead.
- [35:11]
C
Yeah, it kind of fed off the idea of the IL23 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.
- [35:28]
B
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. 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 aisle 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 and to those areas to try to clear it. I don't know what that is, but.
- [36:12]
A
Patton, what do you got?
- [36:15]
C
My second six pack. September 2025, Journal of Cosmetic Dermatology. Randomized clinical trial on the efficacy of oral tranexamic acid versus topical tranexamic acid in treatment of melasma. It was by Hadari et al. This was a single center randomized trial conducted in Iran, or as Iris likes to say, Iran. Quick review. How does an anti fibrinolytic agent even work to treat melasma? UV increases keratinocyte production of plasmin. Plasmin releases arachidonic acid, leads to prostaglandin production, and apparently prostaglandin production can stimulate melanocytes. Plasmin can also apparently increase melanocyte stimulating hormone activity. And TXA blocks the transformation of plasminogen to plasmin, 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 tranexamic acid is very, very effective for melasma. I've never personally used it because I scare the bejes out of patients by telling him 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 that I use compounds it in 3% and 5% formulations. Back to the study, 25 patients were given oral TXA 250 mg daily. 25 patients were given topical 5% TXA to apply twice daily. The results, it was kind of confusing and there, there's like some flat out errors. The endpoint was the reduction in the Mazi score at week 12. That's Masi. But the manuscript like goes back and forth between Mazi M A S I and maci and they do it like a couple times. Mazi is a pretty standard melasma scoring thingy. So they report that the percentage reduction of Mazi 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 Massey score of 6.83 to 4.02 and the topical group went from 7 point. So it was A, almost 8 to 4. So again, systemic MAT, systemic TXA 6.83 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 end Mazi score. That's 58% of the starting Mazi 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 mazi. And when you did topical TXA, you were at 50% of the starting massie. 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 have been statistically significant. I don't know. I still prescribe a magic mix of txa, niacinamide, tretinoin and Kojic 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 like, hey, they did the study and the topical was definitely better than the oral form because yeah, it just, the data was just incorrect the way that they reported it.
- [39:55]
A
So do, do you, so you exclusively, like, do you more or less only use the topical at this point? You're the, the magic mix.
- [40:06]
C
I've never used systemic. I'm telling you, like I brought it Up. And 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.
- [40:15]
A
How. How well does the compounded stuff work?
- [40:21]
C
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. It's. It's one of those drugs where, you know when you're doing skin checks on a regular basis and they're like, oh, hey, you remember that stuff you prescribed? 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? Niacinamide. Nice. Antioxidant. Should be part of everybody's skin care regimen if you actually believe in that crap. Tretinoin. Never bad, right?
- [40:53]
B
Yeah.
- [40:53]
C
Cogic acid. That's a legit tyrosinase inhibitor. Right. I mean, it's funny, I almost did.
- [41:01]
B
This paper, but I didn't. That was recently, like, published in big scientific reports or whatever. And it was a randomized controlled trial of tranexamic acid with niacinamide versus hydroquinone for melasma. So they actually. And they were like, looking at some niosome, like some formulation, and that, that didn't matter. But the take home point was tranexamic acid versus hydroquinone, Similar efficacy, fewer side effects with the tranexamic acid. So I thought that was actually pretty good. Maybe I should have done that paper after all.
- [41:44]
C
Yeah.
- [41:46]
B
So compare. And this was hydro hydroquinone, 4% cream.
- [41:49]
A
Okay.
- [41:50]
C
Yeah.
- [41:51]
B
Yeah.
- [41:51]
A
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 tinted sunscreens. Definitely. Yep. The tinted sunscreens with iron oxide seems to make a huge difference with whatever, whatever the heck else we're doing. That's the, that's the crucial thing.
- [42:11]
B
Yeah. And make it topical. Tranexamic acid.
- [42:15]
A
Yep. That's. I'm gonna. I'm. I'm switching over. I've done just.
- [42:20]
C
Oral.
- [42:21]
A
I've never prescribed the topical. I'm going over to the topical now. You got.
- [42:25]
C
There was. There was one patient in the topical that dropped out because of irritation, so that you did. 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 oligomenorrhea. There was all females in the study. I can't imagine women having a problem with oligomenorrhea, but maybe I am wrong about that.
- [42:50]
A
So that was only in the oral group who got the oligomenaria.
- [42:54]
C
Yeah.
- [42:54]
A
Okay. Yeah, that makes sense.
- [42:56]
C
Okay.
- [42:57]
A
Huh. Because that's, that's what, like it's, it's. I mean sound a little bit weird, but it's got to come out some. Like it, it's. It. Yeah, I'm confused about that. It's, that's. I don't, I don't know what to make of that.
- [43:12]
C
Yeah. 1212 week study. I mean, short period of time, but.
- [43:16]
A
Okay, all right, all right, all right. I'm gonna jump over to my last two. First one just confirms something that you would have believed to be the case. Anyways. So randomized double blind treatment withdrawal or continuation with ruxolitinib cream and vitiligo. 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, if people got better, they got randomized to either stop the go on placebo cream instead of the absolute continuing the opzelura or to continue the opzelura. And pretty much the main takeaway here. So reasonably big study, not huge, like 50 some patients in, in each group. And if you stopped it, the Kaplan Meier probability of maintaining VASI 90. So your face got really, really better facial VASI 90, your probability of maintaining it was only 24%. If you continued it then your probability of maintaining it for a year via Kaplan meier was about 75%. So as you would expect, the main takeaway is if you give somebody opzelure for facial vitiligo 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. Okay, 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 pityriasis lichenoides. So this one was titled Pityriasis like anoides. A university department long term follow up study. So this was done in Serbia and they looked for at long term follow up. So pityriasis like anoides patients, 107 adults, 135 kids and they had long term follow up in this the median follow up was like 9, 10 years, 9.9 years. So couple 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, you know, I was pretty much taught that PLC can last a really long time and PLEVA goes away pretty quickly. And that isn't exactly what it showed. So when you look at the. And also that PLEVA 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 Pleva, so there were 148 people with PLC, 43 with Pleva, and then 45 with mixed pityriasis lichenoides, which kind of look like it could be either one. It was roughly a 50, 50. So PLC was roughly 50, 50 kids and adults. Pleva was roughly 50, 50 kids and Adults. The mixed was a little more kids. So it was more like 6, you know, 2/3 kids in the mixed, 1/3 adults. But the febro ulcerative Mucha Haberman disease, like the horrendous pteriasis, like Anoides, 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 ulcerative 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 Pleva, 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, so wow, they're about the same, but the range was very different. So PLC, the median, the range of duration was 0 months to 144 months or 12 years. In kids it was 0 months to 66 months. And in adults it was 0 months to 144 months. Whereas Pleva, the range was 0 to 36 months. And in kids that was 0 to 36 months. The range in adults was 0 to 10. So it, it, I will. I guess I would say that the longest PLEVO went In anybody was three years, whereas PLC lasted up to 12 years. So even though the medians were about the same or not. 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 these are a really, really long time. And then the febro ulcerative actually lasted longer than I was expecting. So I expected that to be one that was like happens and is 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 you know, interesting. It sort of changed a little bit what I think about the difference between PLEVA and plc. So that, that was. Okay, great. The interesting thing to me and they didn't really talk about this was, you know, treatment. What do you do? So what do you guys do for. For PLEVA and PLC patients? Pat?
- [49:09]
B
I like methotrexate. I've had patients. One of the last ones I had like did. I mean I am Kenalog. I'm not like, I know we're always taught like oh, that's such bad medicine. But like Q3 month. I am, you know, Kenalog 40 really kept her under control. So now I'm like, that's a very simple, safe thing to do. The phototherapy, you know, narrowband.
- [49:33]
A
Okay.
- [49:33]
B
So those are kind of my go to's.
- [49:35]
A
Yeah. Methotrexate, phototherapy, maybe imk. Patton, what do you do?
- [49:40]
C
Isn't doxy up there on pleva?
- [49:43]
B
I think I've had patients where doxy. I do initially I'm thinking more like long term. Yeah.
- [49:48]
C
And yeah, yeah, long term. Yeah. But I think doxy up front. I've used a fair amount and have had decent responses with that.
- [49:56]
A
And it's, I think in kids we're supposed to use. It's one of those deals where in kids were supposed to use erythromycin. Right. Yeah, I think I remember that. That I, I haven't treated kids in a long time but I think I remember like your first line is you try either a tetracycline or erythromycin and then long term. Yeah, I've treated a lot more PLC than I have pleva. Like a lot more.
- [50:18]
C
Yeah.
- [50:19]
A
So methotrexate, low dose.
- [50:20]
B
Agree.
- [50:21]
A
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.
- [50:37]
B
Surprised by that too. But it's.
- [50:40]
C
Yeah.
- [50:40]
B
And like patients always say like how long is this gonna last? Right. And like you to have numbers. I'm. I don't think I'll give them four months. I'm going to give them like two years.
- [50:50]
A
Well, I'm going to give them really variable. You know in some studies there have been people. It's lasted over 10 years. But most people it's a lot shorter than that. Might be a couple years. That'll probably be my my spiel. Ple still, you know, I think I've seen three cases of plea in my entire career that I was like, sure it was Pleva. So that one I'll still be telling people 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 premolast works well for pityriasis like anoid spectrum disease. So that brings up our favorite drug reflu Malast may now be my first line instead of methotrexate for all forms of pyriasis lichenoides disease.
- [51:38]
B
All right.
- [51:39]
A
We will end it there. I want to thank everybody for joining us today. Hope you laughed a few times. Hope you learned a thing or two, but mostly hoping you're planning to join us next week. And until then, I'm Matt Zyrus.
- [51:53]
C
I'm Tim Patton.
- [51:54]
B
And I'm Laura Farris. And we are derms on drug.