Are You Serious? Tattoos Prevent Melanoma and More Curiosities from the Literature

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 in no cost to medical providers. Derms on Drugs is where cutting edge Derm meets Cidermis comedy. Matt Zyrs from Doc's Dermatology and each week I'm joined by my residency buddies, Dr. Laura Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh. We use our 60 years of combined Derm experience to discuss debate and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of Derm and you'll have some fun listening. New episodes drop every Friday on Scholars and Medicine, Apple Podcasts, Spotify and other major podcast platforms and a reminder that the video component has the key figures or tables from the articles we talk about. So this week we're coming at you with one of our patented six pack episodes where we are going to be talking about the stuff that we found most interesting in the literature over the last few weeks or months here and Dr. Ferris, I'm going to kick it right over you to get us started. Okay, so I picked for my first paper, a recent paper in JAMA Dermatology, successful treatment of alopecia ariata with one Jack inhibitor after failure of other Jack inhibitors. And this is by Khalil Craiglow and King. These are the Jack inhibitor alopecia experts out of New Haven, Connecticut. I'm going to give this title, this paper, the subtitle, how to hit the jackpot for alopecia triata. I know. Now, before you go too far, we've kind of covered this topic before. So this is good. It's more information on it where we looked at people who like failed Barry and went who failed Aluminium and went on let full over vice versa or something. And I think the takeaway that we took then was that if the Jack worked some, then there was a but not great switching had a good chance of working. But if the Jack did, if one Jack did nothing, then it was pretty unlikely that switching jacks was going to help. I think that was our take away when we did an episode a few months ago. So that sound great to you, guys. It does. Yeah. I thought like the salt 100 people, which is basically like no hair. Yes. Right. Yeah. I was confused. Yeah. It's salt zero better salt 100 is worse. Yeah. Okay. Those patients typically didn't respond even after a switch, right? Yeah. So if they got no better, they typically didn't respond. So it'll be interesting to see if this kind of recapitulates that. Yeah. So this is definitely sort of a different. This is more of a case series. Okay. So just a reminder, you know, why does this matter? We now have three approved Jack inhibitors, bear a sitnab, i.e. Aluminant, Jack one, two, tick two inhibitor, rentless sitnab, i.e. lit fullo, Jack three tech kind of inhibitor, do rocks, do rocks, a litnab, i.e. lexelvy, Jack one, two inhibitor. Okay. So if you I didn't know a loomie and I didn't know a loomie and got tick two. I know. I didn't really either until I started doing a little reading on this and they said that it actually does. So I thought that was interesting. Yeah. It gets a little tick two. Okay. All right. And so in clinical trials, you know, we don't have had to heads, but we know 40, 45% of patients have a salt score of 20 are lower, which means you have 20% or less of your hair is gone at like roughly a year of treatment. Okay. So this was a retrospective case series out of Yale. So spanning 2014 to 23, 2023. It's only 13 patients with severe, so what they did was they picked people with severe alopecia, out of who failed one or more Jack inhibitors. So, you know, realize these guys were kind of the first people using Jack inhibitors. So they have they were using not just the approved ones, but tofacitnib, you've had a sitnab. And so what they did was they picked those people who failed one, but then succeeded on another one. So it's a little bit of a different question. So what they did do was they said, all right, their key inclusion criteria was they had to have had at least six months on the Jack and that oftentimes their first line Jack inhibitor was sort of an off label one. So you know, they didn't have the criteria of most clinical trials like no concomitant therapy, washouts, blah, blah, blah. So like 85% of these people were also on oral monoxidil and about a quarter of them also got concomitant interleational triumsonal. So you know, what did they find? So in every all these patients, they had failed one, two, and up to like three Jack inhibitors, sometimes, and then they achieved assault less than 20. So these were sort of the people who were like the exception. So they actually had people who went from salt 100 to salt zero. One person actually went through four rounds. They went to four Jack inhibitors before they had hair regrowth. So you know, the the take home here was that resistance to one Jack inhibitor doesn't really necessarily predefined resistance to another. Does it predict it based on other clinical trials? We would probably say yes, but that it can happen. So you know, this was like real world evidence. So I think it's worth it to move on to another Jack inhibitor. It also suggests that they're really not simply interchangeable, which is why I brought up the slightly different, you know, mechanisms of these drugs are different, but you know, sort of, you know, sensitive, our specificities for the particular Jack subtypes. This was small 13 patients. This was not a standardized protocol. Some they switched right at six months. Some were on for 18 months. Lots of concomitant therapy. You know, and so what are the weaknesses? So they do say, you know, we know what the weaknesses are, but well, no, but I would say there are data that would say, and we've talked about this in papers before. When do you give up? We actually like found that up to nine months, right? You can still see response. So six months is maybe too early. I think I would probably do nine. And you know, maybe the magic wasn't in switching. It was just in continued Jack inhibitor for longer than six months. So the other interesting question we now, you know, we've talked about we've got some data that adding I am K, you know, once a month, 40 milligrams, once a month for the first three months, like dramatically increases your response rate using Clubatus all under occlusion, can dramatically increase your response rate. So, you know, would you start somebody give them six months? And if they're not doing better, think about doing one of those things, or, you know, give them nine months if they're not doing better than switch them to another agent. And it's no easy answer to that. It's it, you know, I guess you could talk to a patient about it and see which, which when they wanted to do my guess is that adding steroid on whether topical or systemic probably has a higher faster response rate than switching drugs. But especially if you're doing I am K or weekend dexamethasone or something like that, it might be some risk with that, who knows? Maybe some, but I, you know, I also think it's hard to get patients switched the approval process. I think it I think it is worth it to give them nine months, try adding adjunct. And then also, I thought this was just a good reminder, like add the oral manoxidil. I think when I first started using Jack inhibitors, I know when I first started using them, I didn't really think about that, but, you know, I think you add the oral manoxidil early and continue it on. Do you guys do that when you treat with Jack inhibitor cell? I'll be sure you're ready to do also put them on oral manoxidil. Not every patient. Yeah, not even. Yeah, I like to go monotherapy. That's just my personal preference with everything. Like find the one drug and then just do that one drug and max the dose before you add other things. Probably a different philosophy. I don't think it's any better or just it's an interesting way. So if you don't have to use manoxidil, I like why? Because it's so safe. And if you could have a higher dose of a Jack inhibitor or oral manoxidil and a Jack inhibitor, I'll take a know I said it wasn't right. I know. I'm here to beat that home. I am right or not. It used to be an interesting question with like when methotrexate and sex porn were the only two drugs we had for psoriasis. Would it have been safer to be on 25 of methotrexate or 10 of methotrexate plus two makes per cake of cyclosporin? Yeah. Like probably the methotrexate, but maybe the you know who knows? It's an interesting question. All right, so take away switching jacks can help no matter how many jacks or cells in the past. Third one or a fourth one. Yeah. All right. Let's go patent. What do you got? My first six back paper was from September 2025 edition of aesthetic aesthetic. No, aesthetic surgery journal. Okay. Okay. It's called comparative efficacy and recurrence risk of intralesional therapies for hypertrophic scars and key loids. A network metanalysis by lie at all. So they performed a NMA on 24 randomized control trials for the treatment of key loids. They focused only on intralesional therapies. So if a study had like a lake. laser or cryo or other things, surgery, it wasn't included in the analysis. So this was strictly IL and IL only figure four shows the four's plot evaluating efficacy versus tac alone and Botox, which I mean, I've never done, but I was going like there's some decent data with Botox, but efficacy versus tac alone Botox and tac plus five FU shows better odds ratios for efficacy would compare to other intrelational therapies like BLEO, five FU alone and the RAPA male, which I like vaguely remember, but I never did it and maybe I was thinking I remembered and it wasn't true. So odds ratios of five for Botox and four for the tac plus five FU, compared tac alone. Does anybody actually do five FU and like it's a chemo drug? I think there's like this huge amount of like baloney that you have to do to be able to have it in your office and administer it. At least I think you're supposed to draw it up in a hood and sterile negative pressure. There are all these sort of regulations about drawing it up. There's something called a 503B pharmacy. Does anyone know what that means? It's basically a compounding pharmacy, but they can send it to you instead of sending it to the patient. So people have done that. We love this thing. There are a lot of logistics to it and I think a fair number of providers are like where I'm not dealing with any of that or I need to know way in advance and get enough patients to make it worth my while to kind of get this all set up. Okay. So five FU is super cheap, right? But it's the drawing it up part. So here at the University of North Carolina and I had never even knew this existed. There is some like device. You can put on top of the vial and draw it out. It's like a little makeshift like fume thing. It looks like a satellite TV dish and you have to like put it on and then you have a filter and you pull it up. But we do this and every time I'm like, I don't remember how to do it, can somebody help me. We actually do this and we just have it in our, you know, non-hospital-based clinic without a hood. We have to draw it up through this special thing and the people who know how to do it, it's a little bit of a pain. Like it's got to go into a certain, you know, got to waste it into a certain thing. But once you have the setup, you can actually do this. So we do a lot of IL-5FU for skin cancer. This sounds like several violations and maybe we have to edit this part of this. No, it is not. We follow the rules at the university. It's, I mean, the rules are very different from state to state. It is a state-based thing. It is a foul. Yeah. Yeah. It might be, you know, yeah, whether that's legal in other states or not, who knows? I mean, we are like a state institution, right? Like we over follow every rule and it is, that has been looked at and it has been vetted. So there are ways to draw this up in your office. I'm just going to say. Well, maybe I will, maybe yeah, send me that information. Okay. Okay. So we are doing it. Figure five was a force plot evaluating recurrence and the only treatment that showed a statistically significant odds ratio for recurrence was tack plus five FU when compared to the tack. So it seems like tack plus five FU is better for efficacy, better for recurrence, just the logistics of doing it. What do you guys do for key loads? I mean, with me, I do IL-TAC. I think cryotherapy makes a difference too. So that I do those two. IL-TAC, what strength do you do? It depends on, you know, how many treatments they've had, the color of their skin. Sometimes you're doing tack 10 and if they have darker skin, it starts to lighten a little bit. So you decrease it. I would say if I was starting brand new key, Lloyd, probably tack 20, like try and get as much in there as you can and really soften it. And then I don't think I go higher than that. I've seen some people that go as high as tack 40, but I don't go higher than tack 20. And then when you can kind of give them more and you start to see the atrophy and the hypopigmentation, I'll take it down to tack 10, tack five. Smaller lesions, kind of, you know, they come back and most of the key loads gone, but there's the edge of it that hasn't responded. So maybe there I'll go tack five. I mean, it just, do you have a standard? I don't have a protocol. It's a little bit gistult. But like sometimes like, you know, on the back of the ear, those really firm key loads will be like, oh, let's do tack 40 for the first couple just to try to really smush them down a little bit. But yeah. And I do have a guy here at University of Pittsburgh where, you know, the earlobe key loads where they're so happy because you shave off this huge key loit and you inject and they come back for like one or two treatments. And then they come back a year later and they have huge key loads. For those patients, if they do that, I'll be like, well, we're going to do this a little bit different and I'll do shaving them again and getting them set up for electron beam radiation therapy. So that's my like recurrent key loads. This thing came back because the patient got lost to follow up or whatever and they still want them treated. I just say, all right, second time around, we're going to do electron beam. And there's a guy here that like does it? He likes doing it. You're able to get that cover by insurance? Not. I suppose they do. You'd have to ask him. And I just they like to actually do it the same day of the surgery. So we coordinate the care where I do the shave and then they get radiation therapy that same day. Wow. Yeah. It's impressive. Nice work pattern. Hey, man. Okay. I don't have the little fancy five if you satellite this. I'll send you guys a quick show of it next time I'm drawing it up. It's cool. Next time I'm having somebody else draw it up because I can't remember how to do it. But yeah. All right, let's move out of my got a couple of ones that I'm going to try and do quickly here. So number one, this was interesting that if you get enough tattoos that apparently protects you from melanoma. So this was done in Utah. They used their cancer registry when you know, sent letters out to everybody who'd had a melanoma, got a 41% response rate, and then asked them about their tattoos. And it turns out that the people who got four or more tattoos had a over 50% reduction in their risk of any kind of melanoma or invasive melanoma and people who got three or more large tattoos had a 75% reduction in their risk of any kind of melanoma or invasive melanoma. So this was a really fascinating because it, you know, what it made me think immediately and they talked about this sum in this article was maybe when if you get enough tattooing, it is kind of like immunizing people against some of the antigens in your epidermis. It obviously would be a very weak way to do it because if it was happening a lot, we'd see people get little I go and stuff like that after tattoos, but that'd be kind of the next thing I'd be interested in. But maybe you're priming people's immune system so that when they get a melanoma, they already have some, you know, reactivity. But it was interesting, you know, it's a single study, you know, a 41% response rate, who knows maybe it is real, maybe it's not. I'm glad it's a video podcast so people can see me rolling my eyes and pat and smirking at this study. I may even, I'm like, maybe, maybe not. I just like the, I that you went the next level like, huh, here's what. Here's the mechanism. Was it, wasn't it just like, I mean, did they match for age? Don't younger kids have more tattoos? Yeah, they did a, they did matching and they did that. And rates and, you know, healthcare utilization, I was like, well, maybe they're just like, you know, you're not, you don't buy up seeing all the little ditzel melanomas and say to you because you can't see them because they're like all hidden in the tattoo saying this don't have overdiagnosis. Is the melanoma? Well, that's why they, that's actually why they broke it out to invasive and non-invasive or to overall and invasive to try and make sure and it didn't. So it's, it's something. I wasn't, I thought I saw something about they just, they're more con just skin care conscientious. Yeah, maybe I thought this was fun is now whenever you're doing a skin check on somebody who's got a lot of tattoos. All of our listeners will be smart enough to be like, Oh, you know, it's, it's interesting that you have all these large tattoos that might actually reduce your risk of melanoma. I know. I'm going to tell my patients to take nicotine of mine and get three huge tattoos. Right. All right. Right on. Right on. All right. Yeah. Number two one that I did. So we did a, the malasm episode not too long ago, I talked about ten, or talking about tenet sunscreens. So there was a good study. I don't know. It was good comparison of visible light. Oh, I should say the title. The last one that I talked about was tattooing and risk of melanoma population based case control study in Utah. This one was comparison of visible light protected protective tinted sunscreen to untinted sunscreen to protect malasm patients during summer. Another prospective randomized investigator blinded study. So basically 42 patients with malasm, half of them got regular sunscreen, half of them got and very, very, very similar sunscreen that had some iron oxide and regular titanium dioxide. The one, the other one that was non tinted just had nano titanium dioxide. No other treatment and what was fascinating was that so the people who got just sunscreen their Melasma stayed stable Over the five months of the study and there was no other treatment as far as I could tell the people who got the tinted Sunscreen their melasma got a heck of a lot better Over the course of the summer like impressively better as monotherapy and it it really kind of suggest to me that the reason We've seen Melasma be so recalcitrant to hydroquinone and steroids and retinoids and lasers and everything else is that unless you're using a tinted sunscreen You're not we're not taking away the the underlying problem It was really impressive to me how well the tinted sunscreens worked as monotherapy So visible light is driving Melasma Right, that's what they're blocking is the visible light so yeah The question did they have different Skin types and the study or was it all like fits like four and above four? 99% sure the study was done Yes, it was done in Europe and I think they did actually report that somewhere Let me look it up real quick here The question is because When we did those papers on visible light, I think it was Pretty restricted to darker skin types and the visible light the effect that visible light has on hyperpigmentation So does that mean with like light skin that has melasma? The tinted sunscreen don't matter that and that it's more driven by UV and not visible or is it visible no matter what your skin type? Interesting. I don't know so the by the way in this study it was 93% photo type 3 and 7% photo type 4 okay Yeah, because now I'm seeing those patients right the darker patients and I am mentioning tinted sunscreen You can match it to your skin color and there's some evidence visible light yet to block it But the letters and animations hadn't come on patent. There's not some evidence There is pretty overwhelming evidence to me at this point that visible light is a big factor in Mel in Mel Which is some I didn't say So so but I I don't know what to say to the lighter skin sort of brownish melasma people I could see I Just instead I just told them like for check because it's almost always women Like you just get a tinted sunscreen and make that like your make up your base routine for your makeup and then you're Yeah, I'm gonna help it well. Let's let's move on here. And while Ferris is Blathering on about some ridiculous article. It's too complicated for me. I'm gonna be looking for tinted sunscreen For people with light colored skin see what I can find online. Okay, go for it. This is right Okay, oh do I get to go all right? 18 papers. No, no, you're good. He's doing two. We do one. He does Okay, it's always twice as you know special. Yeah, so that all fit. Okay. Yep. So I picked a paper from J.E.A.D.V DePillium app shows no elevated risk for maternal adverse pregnancy outcomes by I'm gonna call Prusch at all whatever that weird look and be that looks like a beta at the end of it. However, that is pronounced in German So sorry, Dr. Prusch, but you may be Dr. Prue. Okay, so we all know that you know We a lot of times we have we're trading You know women who are of childbearing potential with DePillium app. We don't really have like we got like you know This general sense of well DePixens really safe and there's some good case reports So you know, I think it's fine to be on in pregnancy or maybe we say I'm not super psyched about you being on this You we should switch to topicals, but this gives us some you know kind of bigger data So before this paper them to talk about what was the largest study to date? It was 29 women exposed to DePillium app during pregnancy and they reported no significant You know drug associated risk or adverse pregnancy outcome. So what was this? This is from our old friend Trinetics So they looked at women aged 12 to 55 with documented pregnancy and you know one of the type 2 inflammatory mediated diseases for which DePillium app is FDA approved Who received to do pillium app during pregnancy? And then they created a one-to-one propensity score matched of You know pregnant women was sit with similar diseases and comorbidities who did not get to DePillium app so the primary window of interest was during pregnancy But they also did some analyses for like DePillium app up to six months pre-conception and then in the pregnancy Emphosphardom periods they looked at a couple outcomes were for which that might have mattered so final cohort 200 but 293 DePillium app exposed pregnancies matched to 293 controls for the in pregnancy analysis and You know matched as much as they could like demographic pretty well matched for comorbidities demographics other concurrent medicines like steroids other Biologics etc So, you know what they looked at were it was a composite measure of maternal adverse pregnancy outcomes within 270 days a pregnancy Diagnosis so these were you know pre-term labor gestational hypertension Protonuria gestational diabetes spontaneous abortion and general urinary infection so these papal mire curves yes Were these just women who stayed on doopy through pregnancy or was it like if you were on doopy got pregnant and stopped it you know at week four You know as soon as you found out you were pregnant Could were they still included or was this people who stayed on it through pregnancy did they dispecify that? Not I mean they had to be they had pregnancy exposure I got to be honest. I'm not sure how long it had to be on the entire thing for some of them They were because they also have this cohort that was on like throughout and then up to six months after Okay, I don't know how long you had to be all right Let me just get up. I'll see what I configure out here. Okay So bit the the top line results results no elevator risk of any maternal adverse pregnancy outcomes that they looked at Impatience treated with to pill you map now they also did look at women who had type two inflammatory Disease, you know they had this group that was overall and and the dopilium ab and so one of the things that was interesting was that there was actually a reduction in some of the adverse pregnancy outcomes so specifically in in those women who got to pill you map so specifically if you had type two inflammatory disorders and you were on dopilium ab you had a lower risk of preterm Labor has a ratio 0.11 which is pretty, you know significant and if they looked at the composite like any adverse pregnancy outcome That hazard ratio was 0.53 They also looked at breast infections. I think this is like do you get mastitis if you stay on dopilium ab and the postpartum period And there was no increase in that either so you know large database propensity score matching You know an important result so you know what are the limitations? So this is prescription Records so adherence and exact timing are uncertain, you know, they said in there and then you're of course like depending on coding And then really I think the key weakness here is that they did not look at neonatal or child long-term outcomes So this is only maternal records and they said like for privacy I think it's probably because it's really hard to match so what we don't know is like what happened to the babies, right? Did they have any problems with you know development? Yeah, they have any issues. Did they knock it into Ivy League colleges? We don't know so yes So we can say this is reassuring We can't say this is a hundred percent safe, but you know the things like preterm labor or spontaneous abortion are concerns and the fact that that was a little lower I thought was interesting too Okay, the it and it yeah, it's an interesting thing to keep in mind that there is a risk of having especially uncontrolled type 2 disease You know through pregnancy So it's not like there's not a downside to stopping it. Yeah, right? I thought that was into that figure four which is basically increased risk for adverse pregnancy outcomes and patients with type 2 disease Compared to patients without so if you have a type disease What it was as most off agitists? They actually have worse pregnancy outcomes compared to people that know so yeah, so there's like two cohorts wrongly encouraged them. Yeah, yeah treat at least treat your yes Treating your disease makes sense And they said in the article the reason you so the reason you didn't know is that they had a throwaway line somewhere in there that said We couldn't tell if people stayed on it through pregnancy or Stopped it. Yeah, no, and they kind of said that as a weakness like we couldn't we can't really tell the timing so Yeah, because I think they have prescription data, but not necessarily like they don't have administration data and even if they feel data. Yeah. So the most important thing here is it tells us that it is safe to be undupied while you're trying to get pregnant. And then what I'll probably be doing is telling people, you know, if they get pregnant or don't grade undupied, like the data suggests there's no risk and it might be beneficial to stay on it. But you know, what I would probably do is hold your dupe sent. And then if your exema starts to come back, the second it starts getting worse, restart your dupe sent. You know, see if I can get them off. But then don't let them get a whole bunch of type two inflammation going on, which, you know, is where I think the risk probably comes in. Yeah. And I think it's also important to remember that like you get active transport, um, trans placental transport of antibodies around. And I don't it's like you it's it's well into the second to close to third trimester, right? So like you really shouldn't be getting trans placental transmission of an antibody like dupe sent early on. So, you know, I used to think about, I mean, I don't use to I think about this with women and with psoriasis. If you have a drug that's dosed every, you know, two or three months, you know, maybe just avoiding the last few months of pregnancy and dosing means that you have minimal fetal exposure, but you still, you know, probably don't have bad disease activity. So I think that's another important consideration. So first 12 weeks, you're not getting exposure anyway. Actually, being an interesting topic to have a guest on to talk about, uh, treating women with, you know, managing the woman of childbearing potential and the woman who is pregnant, because it really is, you know, changes the discussion a little bit whenever you start to think about that there is probably not even probably there is risk having uncontrolled disease. So it's not like, well, we should stop the drug to be safe. Stopping the drug might have, you know, say, yeah. And of course, there are drugs where this is not the case where like methotrexate obviously not the case yakine predators very clearly not the case. So you got to make sure that those are stuck. The biologics, the biologics patient, they're what we're talking about. Yes. All right, let's move on. Pat and what he got. All right. Second six pack article August 2025 edition of the BMJ titled efficacy and safety of Ann Rureka Fon and Rika Fon. I don't know. You need to start letting you pick your own papers. Uh, I don't know why I picked this one. This is more of a renal people, but let's just move on. Efficacy and safety of Ann Rika Fon in patients with paritis undergoing hemodiosis. Multi-center double blind randomized placebo controlled phase three trial. They they misspelled hemodiosis multi-center and randomized in the title. It was by Lou at all. Not Rebecca proper English. It was not Rebecca Lou. She was the third year resident. She just graduated. So I saw that name. It was excited. It wasn't her. Uh, Euremic paritis very hard to treat. Don't really know what causes it. Maybe an imbalance of kafa opioid and mu mu. There you go. Mu opioid receptor signaling. More mu opioid receptor activation. That's why morphine can make people itchy and you have a down regulation. Maybe of kafa opioid receptor signaling. So somehow peripheral kafa opioid receptor activation can decrease the sensation of itch. So there are two kafa opioid receptor agonist that are available. IV, Diffolic. I feel like I'm not feeling in the end. Diffolic. I feel like feline. Three hour adboards on Diffolic. Kafa. Diffolic. Kafa. Lone was approved in 2021. It's given as an I.V. medication three times a week with patients hemodiosis. There's actually an oral kafa opioid receptor, but that's only available in Japan. Anyway, this was a multi-center double blind randomized placebo controlled trial. Patients got either an an ric if on 0.3 m. Perkig IV three times a week or placebo for 12 weeks. And then there was an open label 40 week where everyone got drug primary endpoint percentage of patients achieving a reduction of four or more points and a weekly mean 24 worst itch numerical rating scale score from compared to baseline. Little over 250 patients in each group primary input was reached by 37% of patients received in the drug compared to just 15 in the placebo. This was statistically significant secondary end points similarly statistically significantly better for the an ric ifon compared to placebo. Adverse events were similar between the two groups in the double line. Maybe more dizziness with an ric ifon. I just wanted to revisit kapa and mu opioids in their role in itch. And this is more often obviously going to be managed by their renal docs. You know, it's where I will say I haven't seen uremic paritis in a long time and maybe that's because more and more of these patients are getting these kapa opioid receptors. And so we don't see him anymore. First, the diefellic cacalen is reasonably new drug the last couple of years has been on the market. I think the renal people just kind of stop sending the two of us because we weren't much help. The you know, the the the practical aspect of this whole topic, the kapa and mu opioids is intranasal butorphenol, which is the most effective itch drug we had prior to dupy and Nemo. I really it's gotten so hard to write opioids like I don't use it anymore. But that was a it's a combined kapa agonist, mu antagonist. It's almost impossible to get extremely hard to get like hooked on it. You don't get what draw nothing, but it's still really hard to write because it's an opioid, but it it for most people it worked really well for itch. You have you seen dupy, Nemo work like consistently well, not work at all in uremic paritis or you see a mix of that small number of patients that I have seen, but that has worked well and it's in the literature as well as working well. It seems like it was small case reports. They have like a case series on that I'm pretty sure there's a case series about it, but I am not a hundred percent sure and you're talking both dupy and Nemo. Nemo, I don't think there's anything in the literature about it. But I'd be flabbergasted if it didn't if it didn't work and so there was a in august of 2025, there was a retrospective observational study looking at dupy in renal paritis shoot a can of that. But I remember from looking at that and I'm okay, good, I just got to pull it up. It works very well, but let me pull it up here and see if I can get a 11 of 12 patients after eight weeks, 11 of 12 patients experienced at least a three-point introduction. Now it's open label, not randomized, blah, blah, blah. So there's significant placebo effect or whatever, but it worked very well in them and it may have been, I don't know if these people had to have a topic of meditis as well. It doesn't look like they did though. Okay, so yeah, 12 patient case series at least. All right, so maybe I'm convinced. Yep, yeah, it should work. All right, move it on to my last two. So first one was an open label thing about oral jack inhibitors for Velligo. Main takeaway for me was not that impressive. So this was a retrospective series. They had about 96 people who got either TOFA or Rinvoke or Riddle or you know, what are the jack inhibitors we know about. Let's see, or about half of people got 25% repigmentation, only 10%, got 75% repigmentation and most of them had concommonent therapy as well. So most of them were getting Naraband UVB and topicals and whatever. So the biggest thing though was that assuming they do work, which I do think I think they do is very duration dependent. So when they looked at if people got at least 25% repigmentation, so like anything, if you were on the jack for three to six months, you had about a one in three chance of it working, getting some repigmentation from six to nine months. Now you were like, okay, two, almost two out of three, we're getting some repigmentation, same thing, up to 12 months, still two out of three, up to two years, it was still two out of three. But then, but the time you got to more than two years of the four patients who had more than two years, three out of four, had at least some repigmentation. Now some of that is too long. I think nine months are our Jack window, 66 to 75%. Yeah, I would, yeah, I would agree. And the two year number, right? Well, it's like, well, three out of four who did for two. Yeah, but for people who it wasn't working after a year and a half and dropped out, like they're not gonna show up in here. Right. So there's, but my main takeaway was I was kind of expecting them to work better. And the big question with the Jacks and Bitalagos, what happens if you do repigment? Can you stop it or is it like alopecia area to where you lose all your hair? I think that's gonna be. Well, right. And then is it like the same thing with narrow band UVB, right? If you do narrow band UVB and somebody repigments, if you stop the narrow band UVB, they're likely to depigment again. And these numbers that I'm talking about, the majority of these people were getting concomitant narrow band UVB. It's gonna be really interesting when we start to get the face three trials, reporting their data with, you know, Jacks as, you know, standalone therapy in Bitalagos, do they work when I, I don't know if World Jacks are gonna work or not? Is it an interesting question? Yeah, I'm curious. Like I know how much it impacts patients, especially when it's on the face. And I think that's probably, that can be very difficult to live with. Are they like, if they got 50% better? Are they like, you know, this is actually easier managed. I have to put less cover up makeup. Or are they like, this didn't get rid of my Bitalagos, I'm just considering it to be not working? I don't know that they did. Like a vaseline or anything. Quality of life stuff in here. Yeah. Let's see here. Even when they show like, "Opsilore," I mean, I've seen these lectures on opselore and they're like, "Look at how much better their Bitalagos." And I'm like, "Yeah, but they still have Bitalagos." Like you took a patient that had Bitalagos and turned them into a patient that has Bitalagos. It's better, but that person would never walk in the room. I mean, like psoriasis, it's like, you can take somebody who has psoriasis to like, you don't have psoriasis for all intents and purposes. Then with a lot of the Bitalagos therapies, you're not doing that. You're not getting rid of the disease. And so what are patients going to be willing to expose themselves to what sort of risks are they going to be willing to expose themselves to? Bitalagos is very. And there are some patients that their Bitalagos truly does not bother that. So it's just, it's a very interesting. We could have a whole deep dive on Bitalagos. We should do that one day. No, we should do that at some point. That would be good. That day. With that. With Bitalagos. We go on to your next day. No, with a patient, I agree. That patient reported part of the interesting. All right. And then the last one is just a case report, but I know there's ongoing work with this. It's interesting. So, topical timelol, eye drops, right, are used, I don't know, for something optimologically, but they are cheap. And they have some kind of interesting vascular effects, right? So we know they work on. In Fatal and Angiomas, they seem to help some benefit in red scrotum syndrome. There's also some evidence. So there's actually pretty strong evidence that they really help with healing of chronic wounds. This is. There's also a report of them helping with the chronic fissures in erosions of hand-exema. And that is usually the hardest part of hand-exema to get better, so especially with the new topical jacks that we have. But this would make a lot of sense as an add-on therapy to a topical jack or whatever you're using if you've got people with recalcitrant fissures or people who get the little fingertip fissures and cracking. Topical timelol is cheap, easy to get, and you just put a drop on the fissure, or one to two times a day, and it may make a big difference for people. And there are the beta-adginergic receptors are present on keratinocytes, so it certainly makes sense from a mechanistic perspective. Yeah, I thought that was cool. That was my maybe favorite paper. I was like, "You just want something you can do for these patients." Yes. Have you ever patch tested really bad eye-lid dermatitis to their drops? And haven't you seen positive pastor reactions to timelol? So timelol can cause allergic contact dermatitis, I think the probability of inducing contact dermatitis by doing this, so I could see it more if you were using it on stasis ulcers. Which is why I have a little hesitant to talk about it in lower extremity wounds, but yes, it exists, but it's like vanishingly uncommon. I just remember testing and of all the things she had like antibiotic drops and all the, I'm like, the timelol's such a benign, whatever drug that's never going to cause a reaction and her reaction was horrible. Yeah, the interesting thing to patch testing, ophthalmic drugs, is that you want to kind of braid the stratum corneum, like vigorously rub it with gauze or something before you put the patches on. If you're testing to their drops directly in particular. You said stratum corneum and I heard cornea. I'm like, "Man, you do that." But you get to the right answer. They're blind, so it doesn't matter. I don't need to worry. I like it, right? Please sit still. We're patch testing, man. That's a whole new approach for getting your vanillaigo patients better, Pat. Oh, it's, yeah, you're better. It's totally cleared up. You're good. And you blinded them. And then one last thing just to throw in, this was funny to me. So a journal called Skin Research Technology, one day had like 15 articles that they retracted that were all Mendelian randomization studies. And it's just, it is interesting. So I've done a lot of kind of digging at times into Mendelian randomization studies to see if like they're really believable. And it's a general rule I would say they're not. In very specific instances, I think they can be, where there's like an obvious, like, this and this are clearly associated. Here's how they're associated. Here's the biologic mechanism. Here's the whole thing. And now we can, this Mendelian randomization will maybe help us figure out as a causative or not. But people use them all the time for all kinds of stuff. And yeah, it was just interesting. A whole bunch of them retracted. Just, yeah, interesting. But so we're going to stop it there for the week. I want to thank all of our listeners for joining us today. Hope you learned a few things. Hope you laughed once or twice. And mostly we're hoping you're playing to join us next week. Until then, I'm Matt Zyres. I'm Tim Patton. And I'm Laura Ferris, and we are Derms on Drugs.