Genes, Vaccines, Homemade Sunscreens, and More!

[Music] Welcome to 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 health care providers. Derms on Drugs is where cutting edge dirt meets a homeless comedy. A matzires and each week can join by my residency buddies, Drs Laura Fares and Tim Patten, who used 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 to have some fun listening. New episodes drop every Friday on Scholars and Medicine, Apple Podcasts, Spotify, and other major podcasts, platforms. And don't forget there is a video component that has the key figures and tables from the articles we talk about and the episode description has a link that will get you to the links to the articles and other resources we might discuss on the episode. So let's go ahead and get into it. We've got one of our Shraid Mark 6-Pack episodes and we are going to go ahead and start with Dr. Fares. Dr. Fares, what do you got? All right. So I have a paper that was recently published in the Lancet. So I thought that this was interesting. It's a clinical trial called Vital. I cannot pronounce like 50% of the words in this. So it is a drug called a treatment called Prada-Magine Zamacara cell. So we're going to call it PZ. And this is for the treatment of recessive dystrophic epidermalysis, bolosa, or wounds. Okay. So recessive RDEB, recessive dystrophic EB. This is an open label study where the patient was kind of their own control. So this is a FAME 3 study. And so first of all, what is RDEB? Little Board's review for everybody. It's a rare genetic skin disease. It's caused by a mutation in the collagen 7a1 gene, which is what encodes type 7 collagen. So basically, you don't make -- it's a mutation in type 7 collagen. So that gives you fragile skin. You get these big chronic wounds. These patients are pretty sick. These wounds predispose them to infection, deceptus, to anemia, and because of this constant wound healing thing, they get cutaneous squamous cell, carcinomas. And these are really aggressive cutaneous squames that can be lethal. Okay. So what is this drug? So basically, PZ are autologous gene modified cell sheets. So what they did is they took eight millimeter punch biopsies. They made keratinocytes from it. And then they used a retrovirus and transduced it with like wild type collagen 7a1 gene. So they have your own cells that they've grown up that now have normal collagen 7a. And so then what they did was patients had to have at least two wounds. And you know, they picked here's the treatment wound. And here's the control wound. And they only had 11 people in this study who were treated. And so they basically make this sheet. They put it on a piece of zero form. And then they can go it. They go in and sew it in. Patients are hospitalized. The other wound just gets wound care. And then they look to say, you know, what percentage of patients had at 50 and 70% healing from baseline or complete healing. And so they looked at this at week 12 and 24. And so if you look at, you know, complete healing, it was like 16% of the PC group versus zero in the control group. But if you look at who had like 50% from baseline, there's about 81% 80% at the two time points in the PC group in about 16, 17% in the control group. So that was pretty significant. And then they also like looked at pain. So the way that they looked at pain, so it's always hard when you do this with like a control your your own control. So they asked about pain during the dressing change. And the pain score went down by like three points in the PC group and by less than one in the control group. And that was statistically significant. So, you know, I thought this was kind of interesting. I mean, obviously this is labor intensive and like, you know, but now we're doing more personalized therapy. And you know, the other thing is like, this is a one time treatment that you sow this on. And then they had patients with you follow up of up to several years. And so this may be a way to actually sort of fix these wounds and patients. It's going to be a low number of patients. It's a one time treatment. So I thought that that was kind of interesting. We do have two other FDA approved treatments for recessive dystrophic eb. So one of them is called those zoovas. I don't know why they all have terrible names that are hard to pronounce, but it's a bridge bark. A derivative. And then the other one is called Vigue back or something. Or which is a topical gene therapy, which is basically HSV one transduced with the wild type gene. And so you can like put it on the wounds and you can basically try to get the wounds to make wild type college in seven, but you need lots of treatments. So I thought this was kind of cool. It's very, you know, personalized, but disease specific and, you know, rare, but debilitating disease. This is interesting stuff. I mean, this is what they were telling me in 1996 when I started medical school that this was right around the corner. It's only been 30 years, but we're finally getting there. Yeah, I mean, now if we can for how expensive it is to take care of these patients and how awful this disease is, I think it's, you know, interesting to think that we might have more personalized therapy. Yeah, very cool. All right. The late, yeah, like you said labor intensive, they actually had to like surgically enlarge some of the wounds because the sheet only comes in one size. It would be neat if they had evidence that you could actually cut the sheet and then you could put it on wounds of different size. They actually went to the OR and debriefed them so that whatever all sort they were treating was big enough. It's kind of it's almost like they enlarged it, which you would never want to do in an RDE patient. They made the wounds worse and still had these good results really. Right. And they didn't debris the control wound. They just, you know, like did that. And they had photos in the paper. If you look at it, the photos are actually kind of impressive. Like you look at it, you're like, wow, that looks significantly better. Yes. All right. Let's jump on to Dr. Patton's first paper, which has a much less impressive photo to go with it. Dr. Patton, what it went to tell us what you got. So I did uncovering the efficacy of a natural homemade sunscreen and protection from ultraviolet radiation by ints at all published online June 2025 Journal of photo chemical and photo biological sciences. It has what is easily going to win hands down the best graphical abstract that there is. I want to say that the authors like said we're not doing this and the journal is like you have to and they're like fine. And they just made a picture of a guy sitting at a computer using a monitor that has no dimensions of any monitor you've ever seen anywhere searching on how to make a homemade sunscreen. All right. So anyways, so do either of you have concerns about the safety of chemical sunscreens or effects that they may have on the environment. Does that like do you. I don't know. Like I don't like the fact that there's detectable levels of them in the bloodstream. I get that like if you look at the oxybenzone or you know benzophenone five studies you would need 100,000 times as much to get like you're in thickening and all that I get it all but I don't know like I feel like I worry about stuff more than I used to like I worry about microplastics. I would have thought that was a joke five years ago but I worry about everything now so a little bit. Yeah, and I think that's the that's kind of the environment. The of the world now like you know vaccines are bad and pasteurized milk and so chemical sunscreens are kind of falling into that same. I don't believe in either of those things. I know but like when you get on like the wellness bloggers that it's it's all it's unfair to say they're all like that but fair number of them are like this is why I do homemade sunscreen. This is why I'm not getting vaccinated. This is why I don't know who knows what else. I have zero concerns. I don't look at my sunscreen ingredients. I don't care. I put whatever I put on. It's not so I'm not saying like if a patient comes in I don't say oh you're being silly. I just tell them personally like knowing what I know about all of the data that's out there. None of this stuff concerns me. But if you do have these concerns and then I kind of point them to resources where if they have those but some of those resources are homemade sunscreens right so there was an article from 2020. In the journal of cosmetic dermatology looked at 15 different recipes for homemade sunscreens and the SPF and the PF UVA were pretty bad. They weren't in vivo studies it's testing進 on polymath nowhere really in was well not only Mathom Flyscreams like plates and most sunscreens that were tested from this homemade recipes have SPFs in the 1 to 2 range. The best one had an SPF of 5. But you know who knows how those numbers would relate to actual damage in the skin. But the current study compared the effectiveness of one particular home screen homemade sunscreen commercial product, I'm sorry homemade sunscreen to a commercial product. In this case banana boat dry balance SPF, which has all chemical sunscreens. I'm oscillating, octocryling, octosallate, and avobenzone. And what they did was they compared the homemade one to the commercial product on skin samples. So they were taking skin from surgeries that were done, they had leftover skin. So they took these little skin samples, they put on the sunscreen, subjected them to UV radiation. And then they did histologic exams of UV-induced damage. So figure 2B shows how each sunscreen reduced the number of sunburn cells. So they all reduced them compared to no sunscreen at all. And commercial sunscreen was better than the homemade sunscreens. The difference in reduction didn't reach statistical significance between the one day old homemade sunscreen versus the commercial sunscreen. If you look at the graph, it's a huge difference. But I guess it just didn't reach statistical significance. All other studies, like the homemade sunscreen actually was comparable, which you know, that earlier study, if you have SPFs of 1 to 2, I mean they cooked these skin samples. It was 20 joules per centimeter squared. I think if you're outdoors at midday for 40 minutes, you're like a little bit above 10 joules. So they absolutely cooked these skin samples under this light. And when you look at the other things like the cyclobutine permitting dimers, that's sort of the footprint of UVB damage. There wasn't a huge difference between any of the sunscreen study. For the homemade sunscreen, they did one day old and three week old. They also looked at this 8-oxo-7-8 dihydro-2-deoxyguonazine. They shortened it to 8-oxo. That's your sort of UVA footprint damage. All the sunscreens, like were comparable. I would have expected that to be a lot worse. And I question maybe doing it in that lab setting with a little teeny skin sample that you're able to put a decent amount of the sunscreen on. That's not going to correlate to how you're using this in the real world where you're slattering on a much larger area. So in real world use, would this data be a lot worse? One would think. But I was kind of surprised that it wasn't as bad as I expected it. So you're going to start telling patients to make homemade sunscreen? No, because, and this is a lot from the, like if you talk to the chemists, or I watched a few videos on chemists, I went back to the lab muffin sciences with Dr. Michelle Wong. It is really, really hard to make topical medications and to make them effective where you don't have to worry about them getting contaminated, where you have controlled and have dispersed the active ingredient across the thing that you're putting on with these high sheer mixers. Like there was a blogger, another, a different chemist blogger. And for like one year, she tried to make her own sunscreen and then do like the legitimate in vivo SPF, you know, minimal air in the dose testing. And she said it was so hard and sometimes things that did make sense. One time she changed the fragrance and everything else was the same and the SPF went down. And she's like, I, that doesn't make any sense to me. I think that these companies are very highly regulated. They go through rigorous testing to be able to come out to the market and say what they say and sitting at home on a stove using non nano sized, you are zinc oxide powder. There's just no way that these could be anywhere near as good. If patients have the concern, you just point them towards the mineral or the inorganic sunscreens that are out there and they have lots and lots of choices. So yeah, for sure. That makes sense. I mean, so are people like buying powdered zinc oxide on Amazon and like thrown it into some survey and calling it sunscreen? That's one thing that they do. Yeah. But a lot of these recipes are these natural seed oils and other oils and and beeswax pellets and all these other things that they say also have anti-oxidant properties. And that's going to protect you from that would be mostly UVA damage. UVA is the one where it's like sort of indirect damage through these reactive oxygen species. So no, I wouldn't do it. I mean, it's like, I don't know, I'm just lazy. It's like everything else. You can make your own beer and I've done that. But man, just buy it. Well, the amount of beer you drink that would be. You have to go at your full time job. I didn't think we'd make this personal, but okay, fine. All right. So wait, can I ask you one more question on the sunscreen? What do we think? Polypodium, lucatoma, silio care? Anybody believe in that? Oh, definitely works. I think the protection from UV induced damage. Yeah. I think there's a decent data, right? Like MD testing data. Okay. There's other like set you if you go to like integrative dermatology sort of talks about natural things to do to protect yourself from potential sun damage. There's a fair number of things that are very little harm. Is it going to replace sunscreen? I wouldn't take a polypodium lucatomas and not put any sunscreen on. But I think in conjunction with everything else that we do to protect ourselves from the sun, it can help. That's yeah. The polypodium lucatomas is also interesting. I mean, there is some data that if you increase the dose, you increase the protection from sunburn. But I'm I there's not any evidence I've seen that it has doing that makes it more protective against skin cancer, which is the real concern. Or photoaging also a big concern. Yes. Yes. Yeah. You know, there's actually one study showing that if you added it to like narrow band and maybe a topical jack inhibitor, it improves the treatment of Vidaligus. I thought that was kind of interesting. So sort of decrease of reactive oxygen species. So, you know, I'm like, I'm hoping someday we're going to have something that's like an oral medication that can at least provide some sun protection or you know, some of the benefits. Yeah. That's interesting. Cool. All right. So let's jump over to my first six pack article, which was updated expert opinion guidelines regarding the effects of immunosupperson agents on patch testing. So, first, let me just summarize kind of what the recommendations are here for the topical medications. For the area you are going to put the patches on, minimum of seven days for anything that you want not a bit applied in for talking high potency, topical steroids. So, Clubeta's all you want at least 14 days between applying steroids and using the patches. Now, this was an expert opinion. So, there was a big range. I mean, there were some members of the North American contact dermatitis groups that day is fine. Other people said 14 days, but they sort of came to a let's vote and see what we come up with. And in the absence of, you know, the kind of studies that would take to figure this out, this is the best recommendations we're ever going to get. And then for systemic meds, for systemic steroids, recommendation was that people were off for seven days. The recommendation for intermuch of their trimes, synalones, at least 30 days between a shot of that and getting patches put on. Then most of the other drugs that we don't use much of anymore methotrexate in your hand cyclosporin, cell septal, those got seven days. Oral jacks got seven days. You would be phototherapy, seven days. Biologics for a topic, Durham, it said 14 days, but there were two asterisks there that said, you probably don't need to hold these. So it's there's conflicting evidence that they may affect the results of patching to some antigens, but not all. But really the data that's out there suggests they probably don't really affect patchest reactions much at all. And then so the article does have a footnote to that effect. So, I suggest you don't need to hold in a histamine, you don't need to hold. And then the other thing is, well, if you can't stop drugs because if they're just flair so bad that you can't patch test them, generally you can get a pretty accurate patch test on less than 10 milligrams a day. Preden as own, less than 15 milligrams a week of methotrexate, less than 3 milligrams a day of cyclosporin, cell sept, less than 1500 a day. So, biologics for a topic, Durham, says if the biology cannot be held, patch test can still be performed. Biologics may selectively impact patchest results of some allergens. And then for an oral jack inhibitor, the patch test can be performed. And the way that I really think about with Jack inhibitors is if they're on a low enough dose that they're getting some rash, then it means that the dose they're on is not enough to suppress. If the rash being caused by contact arm, the dose they're on is not enough to suppress it. And so you should be able to get a positive patch test to it. So these should not be the case for every single drug. Why Jack inhibitors to a very significant degree? That is how I think about it. If somebody's only partially controlled by a drug, it is very likely that you get a very accurate patch test with it. We just don't have a lot of data to really back that up. But from a perspective of just what's common sense that that makes a lot of sense. So not a ton to really talk about there, other than, you know, it's really useful information. I want to get it out there to everybody because that's a question that comes up frequently. Any other comments from the two of you? No, I like the minimum numbers that they give there, right? I mean, if the patient's miserable, you could say, all right, well, let's take it down this low and you can still get patch tested on that. And it's going to be relevant. It's useful. Yeah. Okay. All right. Let's move on to our next one, Dr. Ferris, what do you got? Okay. So this is from the most recent recently published in JAMA dermatology from Emily Winn and Nanday at all human HPV and actinic carotosis burden, the VAX act randomized clinical trial. So this was done in Denmark. And it was a randomized trial one to one of like 70 patients who were immunocompanied in adulthood, 15 or more AKs. They were randomized to either get GARDISL 9, which is a 9-valent alpha-papillomavirus vaccine or sham vaccine for three doses. And so what they looked at was the percent reduction in baseline AKs at 269 and 12 months from the first vaccine on. And then from there, they looked at like total AK numbers, thick lesions and new AKs over a year. So at baseline, looking at these patients, as you can imagine, most of them, because they have AKs, are patients who are white. However, there are actually a lot more type one skin patients in the vaccine group and more type three skin patients in the control group, which could, you could imagine could have an impact on AK number over a year. So the patients in the control group had more skin cancers in the previous three years. But they both had a civil and number of AKs at baseline. So the other thing to know is that they said, due to ethical concerns, we could not leave AKs untreated for a year. So they both had cryotherapy basically to any Olsen grade two or three AKs in the test area at month six and nine. So there was some cryo, so not like the cleanest thing in the world. But basically, reduction in baseline AKs, basically the HPV group had a higher reduction. So at month two, 35% reduction versus 25% in the sham group, month six, 47% versus 29 in the sham group, at a year, 58% versus 47% although the number, I was like, the number is wrong in the table. Well, to send a letter to jam the derm. Yeah, I saw that it said 4% in a minute 40%. 0.07% it's 47%. The median number, total number at the end of the observation was lower in the HPV vaccinated group. So looked at it, they got fewer new ones. They also had fewer thick AKs. Now did they have fewer skin cancers? No, they did not. It did not that over a 12-month period. That's a short period of time. But they did not. So what do we think? So based on the sort of percent reduction in baseline AKs, there's maybe a 10 to 18% difference in the vaccinated versus sham group. So maybe this is helpful. Maybe it's not, they said maybe this could be adjunct therapy to AK. I know. Other things. People to use sunscreen, right? That alone couldn't treat some AKs. It's hard to count AKs. I've done like one or two AK studies and it's like hard to count to screen AK numbers. They didn't test for HPV in their AKs. So we don't know. And the data on HPV within AKs is more like, I think that's more of an issue and immunocompromised patients, but these are all immunocompetent. And then the other thing was that 76% of patients actually got field treatment outside of the target area of the face or whatever. So you know, could getting PDT or 5FU or a MICWAMOD on your arms impact, could you have an abscule pull effect on your face? We don't know. So it was so bizarre. They said because of ethical concerns about leaving photo damaged people untreated. That's not an ethical concern. No, I thought that was like a little over the top. Like that period of six months. They're going to be okay. We call that like the whole thing in North Carolina. Yes. Photo damaged people untreated for six to 12 months. So yeah, I thought that that was, I mean, I get like you, we will biopsy things that look like scatwarsis vicious for skin cancer, but I think that they sort of made it hard to find a meaningful endpoint. So I don't know that we're going to start doing HPV vaccines. It doesn't really make sense that HPV vaccine much later in life to something that makes antibodies to capsid protein should make a difference and establish HPV disease. But you'll have, you'd have to have decreased number of cancers as you're at point, right? I mean, decrease in the number of AKs. I mean, fine. Yeah. But yeah, if in the end, you're not decreasing the number of skin cancers that these patients get, that ought to be like the only thing that concerns us. I agree. I agree. Yeah. So I thought it was worth the discussion because I think people are going to go, maybe we should be doing HPV vaccines. I don't think it was enough for me to say I'm going to even think about this with the foundation. I'm so happy that the paper exists because, right? I mean, you're kind of thinking what can we do for those horrible patients? But a lot of those patients are also immunosuppressed and that wasn't the population study either. So, right. Okay. All right. Next paper, Dr. Patton. Treatment algorithm suggestion for Haley Haley disease by Giannappolo et al. In the June 2025 Journal of Cutenius Medicine and Surgery. Just a nice quick review, Haley Haley treatments, including conservative measures, topical agents, systemic agents. And they basically came up with a recommended algorithm that I thought was pretty straightforward. So the algorithm there, and I think that makes sense. Before I talk about the paper more quickly, what's like my take on Haley Haley is patients usually come in when it's pretty flared. It's pretty, it looks pretty impotogenized and infected. I typically swab the areas and whatever grows out, those are my systemic antibiotics and when Haley Haley patients flare, that's what I use. And I'll include a viral culture in there as well. I mean, that's how I think of the hairs that I'm going to keep a fair number of my Haley Haley patients under long term. I don't want to say control because they still flare. But that's kind of it. I don't know that I have like a maintenance for these patients. They call when they flare and I give them whatever the antibody cocktail was that I was able to culture. Whatever the antibiotic, not antibody. Sorry. Back on my immunobulose stuff. Do you guys manage Haley Haley any differently? I do not culture them. I can't remember the last time I cultured somebody. I think if they look impotogenized, I kind of just default to doxycycline. Maybe I could be culturing them. Like sometimes you get a gram negative. And then you like to see what the sensitivities are. I have found it to be helpful. But yeah, you're right. Imperic therapy may be enough. And then do you repeat culture them every time they flare or do you kind of treat them according to that original culture? I treat them according to the original culture. And if they didn't respond, I would have them come in because a lot of times they send a message. They're like pretty sure I Haley Haley flaring. I'm like, okay, we'll start these and then let's do a follow up in a couple weeks. So recommendations beyond antibiotics, anything maintenance, like do you do acetretten? Do you do not routinely? Because I hope that between flares they're fine and they're not going to take it. I mean, I can't look, I don't have hundreds of Haley Haley patients, but it's not like I've never not seen it. And that's like that sort of management plan that seems to work. In my experience, I'm maybe completely not recognizing everybody that I'm treating. poorly. That seems to do fine. So basically systemic antibiotics whenever they need them, do you even do TCI's like maintenance therapy kind of nothing when it's long as they're? If I do maintenance, I would probably give them a steroid and say use this a couple times a week when you're not active. But again, like I don't know if they're going to do maintenance. If they have tons of flares, but I've just been lucky with most of my patients. Some other treat, so the algorithm, like I said, is pretty straightforward. Some of the treatments not shown in the algorithm, but discussed in the article I thought were worth talking about really quickly oral anticholinergics because they do have Botox in the algorithm. So for frequent flares, control sweating, maybe sweating acts as a trigger for the onset of disease. Sure. Oral a primalast was mentioned. I think they pulled out like 16 patients reported in the literature 10 with improvement. DAPSONE, but there was only a couple of cases. Immunosuppressants like cyclosporomethetrexate, the litomide, I have not had to do that with my haily, haily people. Apparently, DUPI had some good results. The article of 11 patients treating with DUPI, an improvement was seen in 10. So maybe it's a TH2, like a lot of things are turning out to be. They touch on a blade of techniques, dermabrasion CO2 laser, photodynamic therapy. I would throw in superficial radiotherapy only because I have an article that I published on treating a haily, haily patient. And she was Recalstron. We kind of done all these. It was both. I'd done both. Oh, okay. Yeah. The area is we had the patient with the full body. This was a patient with haily, haily only in a few areas. And she got a lector on beam therapy. It wasn't mentioned in the article. It worked really well for her. There were also a couple other case reports demonstrating the effectiveness of superficial radiotherapy. So if you have a radiologist that's willing to kind of treat those patients, I think that would be a pharmacologist, right? The radiologist. Yeah, what I say? Yeah, radiologist. They can see T-scan. Yeah. Radiation oncologist, they could do the superficial radiotherapy. It worked really, really well for that patient that we published on. Okay. How about, do you think about this like, Darius? How do you think about it? Separately, then haily, haily. It's, yeah, it's, it's kind of a similar type story. Although, I don't culture my Darius. I, you know, Darius, I do think like maintenance, acetretin, I have my Darius on that stuff more frequently. Haily, haily does seem to be, again, for me, bacterial flaring it and treat the, whatever's flaring it. I don't think it Darius as the same way of like flares or caused by this. I, Darius, those patients have disease like in between flares where haily, haily, in my experience, doesn't. All right. Let's move on to our last article here. And this is one that I chose just because it was really interesting and something that was just fascinating to me. So, title of the article was, Jack and Hibiter would draw, causes transient pro-inflammatory cascade of potential mechanism. And they think this might even be related to mace events. So essentially, here's the idea that whenever, that, you know, and we're all kind of familiar with the idea that the way that Jack inhibitors work and the Jack pathway works, the two sides of the cytokine receptor come next to each other that brings two jacks next to each other and they fuss fourially at each other and that puts them in an active state. And in that active state, they then bind ATP and transfer to staff, activating staff. Essentially, all the Jack inhibitors that we have with the exceptions of Rital-Sit-Nib and Dukravisit-Nib, which is not really a Jack inhibitor, they bind to the site that binds the ATP that's going to transfer to staff, but they only bind that site after the Jack is activated. So the Jack has already, it's activated itself, it's been fuss fourulated, so that opens up, it sort of, you can think of it, that opens up its binding site for the other fuss fourulation. Well, when that opens up, that's when the Jack inhibitor binds to it. And so it sort of locks the Jack into an active state. And so as you are on the Jack inhibitor, you're accumulating this Jack enzymes that are sitting there locked in the active state, but unable to do anything because the inhibitor is blocking the site that needs to bind. The fuss fourulation. Well, if you then miss a dose or stop the drug, as it starts to get cleared intracellularly, it, as it comes off, you now have all of this Jack that is built up in the active state. And so it, you get this almost like little spike of Jack's dad activation. And that may be why we see people who will tell me like, oh, if I miss a dose in the morning, that night I can already tell I'm starting to flare and get itchy to which I was always like, man, that is like crazy. Like usually, you don't even see that with like bread in the zone or something where somebody flares that quickly. And so this was just fascinating to me mechanistically the idea of how this might work. So that, does it mean anything terribly clinically relevant? Not sure, maybe we should be really telling our patients, hey, try not to miss any doses. Because it could cause you to have a quick inflamed inflammatory reaction. But I just thought it was really cool mechanistically the idea that we're sort of accumulating the Jack in the active state intracellularly. Just thought it was cool. That's it. I think there's any danger in that? Like could this make people more likely to have like thrombotic events or anything? That's, they suggested that that was possible. That the, there's an increase in urokinase and an increase in interferon that are part of this. And that that might be related to the thrombotic effect. But as you guys have probably heard me talk about whenever I really look at all the data, the the jacks that we have in dermatology, there's no data that suggests that there's actually an increased risk of any of those things. Now, is there an increase risk of those things? I suppose it's imaginable. But we've got a lot of data now around the Jack inhibitors in Durham and there really hasn't been any any indication of a Mesa VTE signal. Remains the case of the reminor suppressive drugs. So that is absolutely the truth. But otherwise, nothing that really is highly suggestive to me. So should we be tapering jacks instead of stopping them? It's a really interesting question, like a really interesting question. And it, you know, how are you going to tape for like go down to 15 and then like you can't do a half a pill. You know, doing every other day wouldn't make any sense. So it's so quick you're saying it's like a fact. Yes. So going in every other day, you might like just be causing this reaction to happen every other day. It's just it's really interesting. We don't know what to make of it. We don't know if it means anything. It is clinically relevant other than this makes blame why people seem to relapse very quickly. At least some patients seem to relapse very quickly if they even miss a single dose. So that's it. Just thought it was cool and interesting. And with that, we're going to close today's episode one of our shortest ever, which is very impressive for us. And so I want to thank everybody for joining us this week. If you got questions, comments or ideas for top cover on the show, shoot us an email of questions at termsondrug.com. Hope you learned a few things. Hope you laughed once you placed and mostly we're hoping you'll plan to join us next week. Until then, I'm Matt Cyrus. It's in pattern. And I'm Laura Ferris and we are termson drugs.