Pick Your Own Treatment Adventure

Welcome to season three of Derms on Drugs and 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 for cutting edge dermis, serious comedy. I'm Dr. Matt Zyres from Doc's Dermatology and each week I'm Joe Memorazan, C. Buddy Stuck to Laura Fares from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh and we use our 60 years of combined experience to discuss, debate and dissect the hottest topics in dermatology. Does everything you need to know to be on the cutting edge of derm and you actually have some fun listening. New episodes drop every Friday on Scholars and Medicine, Apple Podcasts, Spotify and other major podcast platforms and I highly, highly recommend that you download the Scholars and Medicine app to access the full podcast video archive, explore the best derm educational content out there. Not this pharma-generated crap but actual real bread and butter dermatology and it's all supported by an amazing clinical consultant called Ask Simon. So before we get into our episode today, I just have to let our listeners know to keep Dr. Patton in your prayers. He is going to have to have open heart surgery later this summer. It's actually the first of a series of three procedures. Turns out they can only make your heart one size larger at a time. But actually, he is having heart surgery. He just have a aortic valve replacement. Dr. Patton, we're all wishing you the best, Dr. Patton. Appreciate that. Anything helps, I suppose. Okay. Let's get to the recording from the hospital. It's okay. We're not missing an episode over this. You're not going to have any. I don't agree. Turned down his pain meds. He needs to be a little more. All right. Fairies, what do you got? Okay. So my first six pack articles from the British Journal of Dermatology weekly versus daily bathing for people with eczema results of the eczema bathing online randomized control trial, Bradshaw at all. So I guess they get to call it eczema and not a topic dermatitis because they probably don't have such a hard time with prioroths like we do. Or we have to give it official name. Okay. So, you know, this is kind of interesting like we, you know, we make patients feel like, oh my god, don't wash your skin too much. You're going to get dry. But I otherwise you're going to be full of staff. So maybe take showers more and, you know, does it really matter who's going to do this clinical trial? Certainly not me. Nobody's going to get funded. So what they did was this was actually an appraigmatic online recruited randomized trial in the UK. So, you know, how did they get patients for this? They like recruited them on social media, eczema support networks, text general practice. And so people basically signed up to say, I'd like to be part of a clinical trial on bathing. So they screened about 880 people, 438 were ultimately randomized. So like 218 to 20 per arm. So kind of, you know, a good number and they were randomized either to bathe every single day or bathe once a week. And I was like, that was our kind of two extremes, right? Like, maybe every other day, what about a nice arm, but that was not it. And so, you know, was it blinded to it? Was it wasn't? Was it double blinded? Did the patients know how often they were bathing? All right. They put them in the shower and just made noise. But they did point out that this was not a double blinded. They washed them with placebo water. Which was actually like, orm's just, it was tough. But no, there was no blinding. And so they were, so the baseline was that people, you know, you're like, how often do people shower apparently 4.3 times per week? So they had to do either more or less. And so people were actually like pretty good in terms of when you asked them, like, you know, how adherent were you? Basically, like, the adherence was like 62% of people were adherent with it. So that would mean that like maybe they, you know, missed a shower or two or, you know, couldn't handle it and had to take an extra, you know, bath. Like, why did they do it? It was either like, my skin's too dry. I can't do this every day or gosh, my skin feels gross or I worked out and I didn't want to wait five more days to shower. So kind of like the, you know, what you would expect. So what was the efficacy? So their primary outcome measure was the poem score. And so basically, you know, this was all sort of patient reported. There was no easy scoring or things like that. There was no difference. So weekly showering, daily showering, zero difference in the poem score. And it was a four-week endpoint. This wasn't like 16 weeks. There was no like crossover arm or anything. There was no difference in itch. There was no difference in quality of life. Basically, shower, however often you want to shower. So, you know, why was this kind of cool? Like, you know, it was basically an online shower. They were like citizen scientists. So the patients, you know, had input into the design of this study. And, you know, you're going to try and recruit some of those citizen scientists to be faculty in UNC? Yes, because I don't have to pay them. I love faculty. I don't have to pay. That's my whole goal as a chair is how many people can I get to do work for as little money? That's not true at all. I don't do that at all. I'm not doing my faculty well and advocate for them to be paid well because they work incredibly hard. That's right. You know, basically kind of cool. Now we've got some data to guide us on how often people should bathe. And it doesn't matter. Do what you want. My favorite part of this article was when you look at the like forest plot of where the like, whatever, the people who fought that bathing daily was good for eczema, it worked amazingly for them. And the people who thought that bathing weekly was better, they tended like they were in that arm of favors weekly bathing. Yes. So it just goes what patients think work tends to be what works better for them. And that I will say that is honestly what I tell eczema patients, you know, when they're like, what moisturizers should I use? How I'm always like, if you think it helps put it on, if you don't think it helps, it doesn't really matter. Uh, tried, you know, different brands. It's everybody's different in terms of which one they like usually. Sarah V works the best, but you know, everybody's different blah, blah, blah. Because it's true. They were on a commercial for them. So there's a hat that might be it. They only ran that commercial like three times. So I'm kind of mad about it. Mostly in like South America, I think. But yeah. Yeah, they dubbed them. They overdubbed them. Hola. Mi si amo matruzitis. Because if you tell them like you have to moisturize, you have to moisturize, that makes them less compliant with the stuff that really does help. Like, we know the more stuff you tell people to do the less stuff that they actually end up doing. So that's the, you know, okay. No, it's fine. It doesn't work. So it was a good reminder of that, but yes, it doesn't matter how often you base, do what you believe in and it will work the best for you. That's great. That's right. It's all relative. There's no truth. Exactly. All right. Let's move on. Pat, and what do you got? Let's give us some truth. My first six pack papers from the March 2026 JAMA oncology and is titled morbidity and mortality outcomes of de PiliMembre for cutaneous immune related adverse events by block at Al. So some background, there's a 2025 paper in journal of immunotherapy of cancer, retrospective study done at mass gen and Dana Farber, I think that compared patients with bad, I'm going to call it ICI, immune checkpoint inhibitor rashes that got Dupy to two other cohorts, patients that got bad ICI rashes and didn't get Dupy and patients that didn't get bad ICI rashes. The take on points from that previous study where that Dupy worked like close to 90% of patients had complete or partial responses and there was no statistically significant difference and mortality between the groups. High-dose steroids associated with worse outcomes, blah, blah, blah. So the current paper is a trinetics study, so not believable at all. We're thinking. The authors took patients with ICI rashes that got Dupy and compared them to two groups. They compared them to patients with ICI rashes that didn't get Dupy and patients with ICI rashes that got systemic steroids. Propensity match scoring done to match patients for a bunch of stuff and the primary endpoint was all caused mortality at five years and the results are represented in the figure, just one figure, couple tables, one figure, just kind of crazy absurd hazard ratios, right? Dupy compared to non-Dupy, 0.31 versus the steroid controls. So that's close to 80% 70% improved mortality if you got Dupy for an ICI rash. They reran the data with the sensitivity analysis, still kind of crazy hazard ratios for mortality. So yeah, I mean, it's just it's it's not believable. I could see where doopy might help a little bit And I don't think it's really the fault of the authors. I think all the statistics probably check out It's just that I like I don't think trinetics is Providing anyone with like realistic data. I've got an alternative explanation coming patent. Oh, let's hear it Okay, so let's so we're we're gonna segue into my segment of Of the six pack so this was a study which I had never really seen this before The effective pre-existing atopic dermatitis on clinical outcomes of immune checkpoint therapy and so having a D made Immune checkpoint now. This is also a trinetic study. So I got a gotta be honest. It could all still be baloney But having pre-existing a D Dramatic made you much more responsive to immune checkpoint inhibitor therapy. So they had a much higher rate of getting the adverse events So 5.93 hazard ratio of getting a container immune related event Increased rate of endocrine events increased rate of GI events But they had better substantially overall survival so Let's see here pre-existing a D had lower all cause mortality 0.56 so you were twice as likely or half as likely to die if you had a D and a Got immune checkpoint inhibitor therapy and they're they didn't really look at it in terms of like severity But it is meaningfully Suspected that that is an important part of it And so that I dug into this today because I was like that does not make any sense to me at all because I think of cancer as TH1 immunity and TH2 immunity like Smushes down your TH1 immunity and here's what I found out it turns out eocene fills they are learning Have a very significant anti-cancer activity and so there now is the number one eocene fills have anti-cancer activity and number two IgE is much more potent as a Comcolitic something or other than IgG and so now there are some reasons and and across the board I guess it's been known for a while that people with a D tend to get less cancer than people without a D But the immune checkpoint inhibitor thing they think the other thing is happening there is that the T regs are Acting as sinks for IL-2 and so when you've got a lot of T regs because apparently your body up regulates T regs to try and control the AD and I'm making all this up by the way in case anybody is like a basic scientist out there like But yeah, I could see Ferris twitching a little bit So I didn't but I didn't read up on this today so the The T regs act as a sink for IL-2 and Your whenever you do immune checkpoint therapy one of the things that happens is your T regs go down and when your T regs go down If you've upregulated your IL-2 because you had so many T regs now there's more IL-2 which is also anti-cancer So it it like there are multiple mechanisms By which being a topic might make you more responsive to mean checkpoint inhibitor and it may be that the Dupy is a just Marker of you have bad atopic dermatitis so these mechanisms are even more operative in you Yeah, I thought it was like it wasn't exactly contradictory, but it was like if if you looked at your paper and you said okay Having that sort of TH2 hyperactive immune system helps you fight cancer Dupy is anti-th2 so you would think okay Well like if we're gonna be consistent between the two papers It should show that Dupy actually makes cancer treatments worse And it was the opposite yes, and their takeaway was that The takeaway that I found when I was taking into this that the eos are probably the best explanation because Dupy is kind of Pro-eo like we know that when you start on Dupy you get a transient eosinophilia Because it the particular you know IL-5 is the eosinophil one and so Dupy doesn't block it at all so it it might be that it is Almost stimulating your the eosinophil part Of your immune reaction Actually, there are and I was looking there are a bunch of like Pretty much looking at Dupy in cancer treatments Yeah, a fair number. There's like five trials ongoing. They're like we're just gonna add Dupy to Standard immune checkpoint inhibitor, right? I mean we'll have the answer those companies needs to send me some checks because like a year ago I was like Dupy needs to do these In fact, I Lord the Lord's husband for an of our listeners is like in charge of cancer at the University of North Carolina And I told her to tell him so if there any trials going on at UNC I am taking full credit for that You got senior author status on every single one of them. You're good. I don't know if I told him We I talked about you a lot, but I did not you'll be acknowledged. You'll be an acknowledgement That would make a lot more sense. I don't want to have to read the papers I do I want to say You know Dupy's used to treat COPD, right? So what do people with COPD? They smoke they also get a lot of lung cancer I do believe that there's better survival and lung cancer patients on Dupy I or either that was a stud somebody was looking at or it's been shown so like that will be a really interesting place to look at the Dupy cancer thing we have looked at this a couple times like I think at the very least we can feel pretty darn comfortable Dupy does not increase cancer risk if patients have cancer we feel very safe Having them on Dupy whether it is to treat their side effects of immunotherapy or for their underlying disease since they have like 11,386 indications for Dupy now, so I think that's just generally good for you. That's all. Yes, right? All right, jump quickly to my other one. This one's just a fun one granuloma anulare One of you know, I like looking for like weird treatments for weird stuff. So GA There was a paper hyperthermia for granuloma anulare and basically and I reached out to these Chinese authors to find out like the specific Regimen that they used so they use local hyperthermia 44 degrees centigrade Which I think is like 120 degrees Fahrenheit or 110 120 patent looked at up At for granuloma anulare pilot randomized controlled trial so they did 30 minutes once a week on the most recently developed lesion and They did like randomized controlled trial, but there were like four people in each arm. So like kind accounts It was like stunningly effective like the pictures they have it's like wow And so apparently heating up granuloma anulare Makes it go away and even some of the patients who had like widespread did one of them had widespread disease and they got a lot of their wide spread GA Got better it somehow affected the systemic immune response So right if this was like a $10,000 thing no, I wouldn't be like who we should all be doing this But you get a heating pad from what I could tell when I looked it up was basically said the heating pad to medium Put it on your GA lesion for 30 minutes once a week do that for three months usually they were better within like a month It was so once a week heating pad so maybe the full body see the problem is I saw somebody with GA today I was like I guess I'm just gonna inject it Because I had to work all day you just sit and pick papers all day and you didn't have uploaded for me to read I'm the only derma and drug who works on monday so I'm gonna put that out there um and so You get on some more drugs there it's gotta be something I have a heart problem I would like to Thank you you've got an excuse for now till you get surgery then I want well He's always had a heart problem now there's a structural problem with his heart as well Um, okay, so then like I you know, I think I remember seeing this paper like I wonder if you put people and you know like those Sauna's right? infrared sauna Oh my gosh first that for like the people with widespread GA that's genius You write them a script for and then they can use their HSA dollars Uh to to pay to go to the infrared sauna it wasn't an infrared device that they said they used in the study Yeah, that's that's actually more literature supported than the heating pad The it's 112 degrees and I do want to point out that one of the patients had a lesion on the penis I don't know about that I don't think I'd be like yeah peeing it up Yeah, this maybe it was it was that it was the syphilitic variant Uh But so that's it just so the fairest such genius the infrared sauna for widespread GA because people are paying in the butt to treat And for localized yay Just you know do a heating pad at home The back of their hand the top of their foot whatever I they did just one lesion they didn't do all of them But it was it was impressive like it was impressive those pictures easy to get cheap All right, everybody's got to try it now. We're going to report back to see if it works. Okay, all right. We're in. All right, let's move on to our next paper, Dr. Fares, what do you got? Okay, I'm going on the kind of sort of AD theme, which is a paper in JAMA dermatology also out of, I believe, China's you at all safety and efficacy of ICP-332 for moderate to severe atopic dermatitis phase two, RCT. Okay, what's ICP-332? This is a tick-2 inhibitor. You're like, well, don't we have a bunch of tick-2 inhibitors? This one's different because it binds to the GH1 catalytic domain. So everybody who's been to like a do-crabacetinoptock or anything from like Takeda, you're like, you know the word alistairic inhibitor, like, you know, the back of your hand. So you know that those don't bind to where the ATP binds. It binds, but this one's different. It binds to the catalytic domain. What does that mean? It binds like the catalytic domain is not just in tick two, it's in Jack 1, 2 and 3. So this drug does have some Jack 1 activity unlike the typical tick twos, but it's like 40 times more selective for tick two than Jack 1, but the other ones will be like we are 5,000 times more selective. So what's it doing? So it's kind of got like a tick-2 favored, it's like a tick-2 strong Jack inhibitor. And so this was a double-blind placebo-controlled phase two trial 19 centers in China. So there it is all Chinese people, their eczema, their e-topic germs, probably different, you know, than what you see in like sort of the broad spectrum US population. 75 patients total in the study 25 per arm, so small study. Placibo, 80 milligrams or in 120 milligrams a day. Primary endpoint? Four weeks, okay. So this is also like a super short study. It is, so yeah, what does that mean? Like the single oddball event can throw off the results, like the single oddball super responder, the weird, you know, whatever, AE. So the efficacy parts kind of interesting. At week four, reduction in easy score was 78% and with the 80 milligrams dose and 72% with 120 milligrams dose. Like that's a pretty darn fast significant easy response. Yeah. And so and it was 16.7% with the placebo. So not nothing but like that's a pretty big difference. Okay. That is the technical term, Dr. Ferrison, ginormous. ginormous delta. Yes ginormous delta. Okay, how about easy 75? The placebo adjusted easy 75 responses 56% and so if you look at like what that means like easy 75 of drug minus placebo. And so like what does that look like for a jack inhibitor? That's like kind of up there with like you pat a sitenibs at 12 to 16 12. I think their primary endpoints are 12 weeks. So you know that is, this is not a, you know, had to compare some blah blah blah. But like it's pretty, you know, impressive. Common AE's, the things that you would expect. The one weird standout AE was decreased fibroinogen levels, which occurred in 24%. We never looked at that in our like jack inhibitor studies that I could see. So I don't really know like so in theory I was like what would decrease fibroinogen do? So again, we worry about like clotting events, but really decreased fibroinogen would maybe be associated with increases in bleeding. So you know, but there wasn't like bleeding in here. It's just like that was like their thing decreased fibroinogen levels. So there was one case of rabdo and the 120 milligram dose. Interestingly, the 80 milligram dose seemed to work better than the 120, but 25 patients. We don't know what that means for arm. So there was one case of rabdo and like every single jack inhibitor study, what did they say? Well, that person was really exercising a lot. So people in jack inhibitor studies decide to take up exercising a lot. So that's really what it was. So, you know, small study early time point, you know, I just think it's going to be interesting to see where this goes. You know, and if you look at some of their other like BSA, like decrease in BSA was like, you know, from baseline, like 20, I'm trying to see what their baseline, I didn't like look at what their baseline was, but like while the baseline was decry by the decrease in baseline in BSA four weeks was like 5% in the placebo group. It was like 25 to 30% in the in the active treatment in the the tick two inhibitor group. You know, patient, send to patients getting to like IGA 01 was like 36%. It's pretty good. So mechanistically, this is pretty similar to breppo, brepo, sitnib, is that that's the dermatitis I just want to say that that's like that jack one tick two, right? Yeah. Right. And that drug has been like spectacularly effective for dermatitis. So I wonder if like that mix of jack one and tick two is like some magic, you know, you block those two and woo. Yeah, interesting to see if they try that. I mean, even just tick two, if you look at do crab, a sitnib, it's probably better in like, you take like connective tissue disease like lupus that or dermato than it maybe even is in psoriasis. So, you know, I don't know. I think it's interesting. We got a bunch of tick twos coming out. Might they be the answer in atopic, derm? Perhaps they will be I will say that also in the study, they did like follow people after their four weeks, they withdrew the drug and then followed them. Itch went up, easy score went back up, BSA went back up like they did it. It wasn't a sustained, you know, response, but it but they did, you know, it wasn't it also did what you would expect. So I just thought this was an interesting one. Don't companies freak out with lab abnormalities? Like isn't that enough to like shut down a drug? There was a a brutal on tiresy and kindness inhibitor. I think it was fennabrutinib for CSU and it worked great, but they were getting like these little bumps in LFTs and the company was like, yeah, forget it. We're not even going to try. So I don't know, we're low fiber in agents sounded scary to me and it was in both it was in both arms. It was in the 80 and the 120 and it was up to a quarter of patients. Yeah, it's a high number. I guess I don't know enough about the clinical significance of that to know. And you know, I don't do all our tick two inhibitors do the same thing. We don't check it. And I've never seen, I went back like, you know, to look and see like, do we have this in the de-cravissant of studies? It wasn't monitored. It was specifically monitored here. I think it was based on data from another study. So yeah, that's the thing is they had to be a reason they're monitoring it because it's not like a normal thing anybody would be monitoring. Yeah, maybe it's measuring the synthetic capacity of your liver. Something like that. Yeah. Yeah. And they're like, their liver function otherwise was normal. So, you know, it also made me again, because we've got all these other tick two inhibitors, a round, but not being really pushed for psoriasis or in development, like maybe a topic derm will be the next you know, frontier for them. This segment about fiber in agents making me think like if aliens were like listening to the podcast and we're like, these are the three dermatology experts in America. And we're like, Oh, for pretty, I don't, you could be out. I don't know. Is it clinically relevant? Yeah, we're the experts. That's that's that's great. I never thought about our Spotify metrics as listeners. It's all good. But if they don't have like accounts, it doesn't matter. We don't need them. All right. Let's move on, Pat. And what do you got? All right. My second six pack British journal dermatology March 2026 titled Baph April blockade with telatacet and Pemphagosfoliacis two cases by Wang at all. So what are Baph and April Baph is B cell activating like, I guess it's a factor. There's two Fs, but it's called B cell activating factor. So no, B cell activating. I think that's good. We'll go with that. It's also known as B lymphocyte stimulator. So it's sometimes abbreviated as blis VLYS. April is a proliferation inducing ligand and Baph and April are cytokines that buy the B cells influencing their activity and survival. One of the receptors to which they both bind is known as tassi TACI. So telatacet is a fusion protein Fc portion of an IgG and the tassi receptor. And it's so sort of kind of sucks up Baph and April, the two cytokines theoretically not allowing in divine to B cells. So the paper reviews two cases of Pemphagosfoliacis 22 year old female, 44 year old female, both refused systemic corticosteroids. Like, man, Pemphagos, like, I don't know how you could ever get a patient better, not using systemic corticosteroids. So this is kind of monotherapy. They were both on minicycle, and I don't really think the tetracyc and antibiotic do much for pempagus. One was also on some weird like Chinese medicine thing. Both patients were given telatastasept 160 milligrams weekly by subcue injection and both patients improved. So PD/AIP/DI measure of pempagus severity dropped to zero in both patients, one by week eight, one by week ten, that's pretty quick. And the anti-desmaglean one antibody titers dropped, one patient they went from 596 down to two, and the other one it was 209 down to two. So maybe a promising drug, I mean it was kind of a dumb paper, I'm known for this, it's not FDA approved to treat anything. It is actually approved in China to treat SLE, rheumatoid arthritis, and generalized my stenia gravis. So it's being studied for some autoimmune conditions, I think it got fast tracked here for showburns. And so maybe a promising future pempagus treatment, I mean it's almost like you do have to hit B cells, right? You look at retoximab, you get you hit B cells. This is kind of like a softer hit on the B cells, but maybe an effective therapy. So nothing that's clinically useful for anyone outside of China, so you're welcome. Good night. It's a good B cell tap. For somebody who's looking to do a little medical tourism, you know, just get on that 14 hour flight to China, and you get there, get your tepolacolidlib. That's exactly what it's called. Good. I'd like someone to go to China and ask for that. They'd be like, go back, we don't have that. There is no such thing. But Dr. Zaire said. Exactly. I think I'm banned in China to be honest. That's likely China and Iran. Those are my two. All right. Remove it onto my last two. So first one, just interesting. So this was a study out of, believe Indonesia, where they were looking at scabies and then people who after they got treated for scabies, how long their it's persisted. So relatively small study, you know, reasonable chance that these people had like co-other stuff going on, whatever. But the, I mean, I'm pretty fascinated by this. So the main takeaway, people who had a long term post-cubedic itch, universally, not really universally, but have really high IGE at baseline. So you could measure IGE at baseline. And then that predicted very effectively that you were going to have a prolonged post-cubedic itch. And that's very plausible to me. So like I think of it as being that, you know, scabies might were allergic to them. It certainly is possible that people who are atopic or driving more allergy to them. And it's going to take longer for the inflammation in the itch to like resolve. If this was like a super hard test to get, yeah, I'd be like, like, I don't know, or if it was expensive or you got to send it off or whatever. But like this is easy. You do, you know, an IGE test. If it's, if their IGE level was super elevated, you then you tell them, this might take a while. Or you know, so just thought it was interesting. Then the other one that was even probably more interesting to me, but it's mostly mechanistic, was about sort of a different approach to food allergy and atopic dermatitis. So the idea is that with chronic skin inflammation, high alarmons, so IO33TSLP, you drive, and this, I think Ferris has talked about this a little bit. You drive TH2 sensitization to weak allergens, especially in the gut. And so essentially you become cutaniously and maybe maybe be a gut route sensitized to things like propylene glycol or propolis or whatever. And then that's driving a systemic TH2 inflammatory state that you could in theory get better via dietary avoidance. And this would go to some extent against my frequently repeated, like thing. Look, just put people on the IGE 13 inhibitor. And if they get better, you know, it was a topic, Durham. Well, no, if it's because right because contact dermatitis, TH1 disease. Well, but if there's this other type of TH2 contact, or associated specifically with systemic contact, or that then doopy would work for that. And then maybe those are people we could get better with a avoidance diet. However, my final take on the whole thing is if avoidance diets worked, we would not need statins and we would not need blood pressure meds. We would just say avoid, you know, foods that are bad for you and people wouldn't die of heart attacks. But instead we have all those drugs and we have cabbages and we have cats and the whole thing. So I'm still a blip if you told me like we could do all of this testing. You do all of these avoidance diets and be super careful with what you eat for the rest of your life and you won't need to whatever. And it's going to take a year to figure out if you're one of those people, I would be like, just give me the doopy. Don't care. Like I'd give myself a shot every two weeks and if my insurance is paying for it, then we can come back and try and figure this shit out. Like that would still be my take on it. But I'm not be everybody's take just an interesting thing. I'm not sure what to do because kind of what they recommend is at to be patch testing, which is like sort of a modified normal patch test, especially their patch testing people to different stuff and you're reading the patch test a little bit differently. But like nobody does this. There's probably like 10 people in the country who do it. So like, you know, unless other people start going it, even if this is real, it's hard to like figure out other than going in purec food avoidance. Yeah. And there's no like ordering a test to the food, right? Like, you know, no, no, it's so hard when people come in like, Oh, look at this. I got the, I saw the allergist and I'm allergic to 18 foods. So like, yes, or even better if they went to the, yes, they went to the functional medicine doctor and got food, IGG testing. And like any allergist you talk to is like, IGG literally means you are not allergic to it. You get IGG that is specifically like we test that to prove like you're not allergic. But like since it's a positive test, people get, whoa, I mean, a positive test to the, you know, corn. Yeah. But so just mechanistically interesting. These guys, I've had a strongly held belief about this TH 2 skewing stuff as baloney. They convinced me that it's at least like possibly not baloney. I know I now give it real credibility that we couldn't have this as another contributing factor to the rise in a topic of appetite is over the last 40 years. So yeah, I mean, it does like also like kind of back up like that. And we've had Peter Lee along to talk about the gut skin access. And I was like off the gut skin access. Like maybe it's real, right? Like there are some now explanations that there may be, I don't still don't know what I think about leaky guts, but you know, maybe there is something to all of this. Oh, it's, I still think of the microbiome as the, you know, intestinal microbiome is the best. But that's maybe there yet. It's, it's complicated. It's complicated. It's, it's like our kids, no, no, my kids probably know you guys as kids either. Some of the normal kids dating lives. It's complicated. That's what we'll go with. All right, we're ending the episode there. I want to thank everybody for joining us this week. I hope you learned a few things. Hope you laughed once or twice, but mostly we hope you're planning to join us again next week. And until then, I'm Matt Zyrus. I'm Tim Patton. And I'm Laura Ferris and we are Derms on drugs. [BLANK_AUDIO]