[Music] Welcome to Derms on Drugs. Video podcast brought to you by scholars and medicine, the best platform for education and dermatology and provided or no cost to medical providers. Derms on Drugs is where cutting edge dirt meets hitter miscomedy. Matt Zyres in each week I'm joined by my residency buddies, Drs. Laura Ferris in Tim Patton, where 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 known in the cutting edge and you'll actually have some fun listening. New episodes drop every Friday on scholars and medicine, Apple Podcasts, Spotify and any other major podcast platform you might use. And just a reminder that this is a video podcast, so if you want to see the key figures from the tables, they're in the video part and then on the scholars and medicine platform, the links to all of the articles we talk about are there. So this week we've got one of our patented six pack episodes where we are going to go through what has been the coolest, most interesting stuff we've seen in the literature over the last few weeks and we are going to start off with Dr. Ferris. Dr. Ferris, what do you got? All right, thanks, Cyrus. So I have a paper from Lancet rheumatology, Hague and at all, local immunifactor cell associated toxicity syndrome and CAR T cell treated patients with autoimmune disease and observational study. So that's a lot. So I picked this because it's kind of interesting. It's a new, like newly described chemotherapy or drug toxicity. So we are going to call this lycat. Okay. So this is an observational study of thirty nine patients. First, wait, I got to stop you first just because I'm too far behind to even start here. What is what is CAR T? Like what is the therapy here? Are you going to get into that? Well, so the therapy are these modified T cells that are engineered to target CD-19. Okay. So instead of having like an antibody that depletes CD-19 T cells, you have the, sorry, instead of having an antibody that depletes CD-19 positive B cells, you have this modified T cell that does the same thing. Now this is sort of CAR T cells were originally developed to treat like hematologic, mostly malignancy. So it's basically an engineered T cell that attacks, in most cases, a tumor cell, but they've been engineered to actually attack CD-19 positive cells, which are going to be B cells. So these are T cells. I mean, this is like for the worst of the worst autoimmune conditions. They, like, take the patient's T cells out, genetically modify them, and then put them back in. Or these just some random persons T cells. No, it's not some random persons T cells. They are your own T cells. It would be dangerous. It would be a little bit different. I'm sorry. I need you a problem. I should have specified. Okay. All right. So this is almost the equivalent of retuximab, like, but instead of an antibody, we're giving people cell mediated, which should be denser and more effective. And longer, like, what's the -- Yes. It should be more targeted, more effective. And so interestingly, because it's relevant to this paper, what they say is these are better at penetrating into tissues, and depleting B cells within tissue. And that's why they think they're actually better at treating autoimmune disease. So you take harvest the patient's T cells. And then you -- You engineer them to react to CD-19. You then basically, like, cytodeplete these patients, right? So you give them, like, cytoxane and fluid aerobene. And then you give them back their these modified T cells. I mean, this is like serious business. This is not something we're going to start doing for every disease. But it is done. And I assume they use it -- When they use it for cancer, I assume that they can, like, make it to gen that is specific for that cancer. Yes. They could -- yeah, it's not all CD-19. So you can sort of modulate these to be, you know, specific to whatever disease you're treating. Pat, am I -- You might say that all right. Is there anything you'd modify to what I'm saying? No, that's right. Except, I mean, our isn't 90-some percent of CAR T cells, like, CD-19 is the target or -- I think that that is -- I think that there are more -- So CD-19 targeted CAR T cells can be used to treat the cell malignancies too. But, you know, there's also been, like, CAR T cells that have been proposed for treating other auto-inflammatory diseases or other malignancies. I think -- I guess I'm thinking of ones that are commercially available. I assumed it was only the 19s. I could be wrong then. Okay. Yeah. I have read about them in studies. I got to be honest. I've never had to look at doing this for a patient. So -- And this is different than tumor infiltrate, because I -- And cancer, they talk also about tumor infiltrating lymphocytes. This is different than Tills. Tills are your own tumor harvested. You take out the cells. You grow up and activate the cells and give those back. Okay. So those are going to be, like, polyclinel. So this is your own T cell modified to a TAC CD-19. All right. Okay. I'm all cut up there. Now I'm ready to hear about that. How you're ready. Okay. So this is looking at using these not-to-treat malignancy, but to treat, like, bad auto-immune disease. Observational study, 30 patients, 20 had SLE, 13 systemic sclerosis, 6 had idiopathic inflammatory myopathy. You know, like, 2/3 were women, as you might expect. So what they -- they described these local reactions, which they called lycats, which is local immune affector cell associated toxicity syndrome. Okay. So the reason I picked this is just like, this isn't something that I think about. And I think about toxicities to immunode or chemo, you know, to therapies or to any drugs. So they found that 77% of patients were affected by lycats with a median time of onset of about 10 days. Now, this differs from when you give car T cells, you think about something called cytokine release syndrome, which is basically like massive T cell activation in your tissues so you get, you know, massive inflammation, hypotension, these patients can get pretty sick. This is differentiated from that. So what they found is that this occurs exclusively during the B cell, a plasia phase. So basically, when you have all your B cells have been wiped out and you've got no B cells that you get this reaction. So it's only -- it's only involves the organs that were affected by the autoimmune disease. So yeah, so it's really interesting. So like if you had cutaneous manifestations of your disease, i.e., the SLE patients, you got skin toxicity. If you had lupus nephritis, you had renal toxicity. If you had myocytus, you had, you know, if you had myopathy or myocytus, you got muscle disease. So and most of these were actually like relatively mild. They went away with some prednisone. And only a couple were significant. And so if you compare this, you might be like, okay, well, we do this with like, we're tuxan, or, you know, CD-19 targeting antibodies. And it turns out that you don't get this. And the authors, you know, argue this is because they don't really deplete the B cells deeper in the tissue. And that this is something unique to the fact that, you know, you deplete the B cells and that that is, you know, driving this immunologic resetting and, you know, triggering a stable remission, but that in the process of this resetting, you can get this auto inflammatory. It seems more intuitive to me that when you give the antibody, the antibody just attaches to the bad cell and kills it. And, but this you're giving these cells that they then like, dock up and like release stuff that causes an inflammatory reaction that you wouldn't get with the antibodies. Why is that, that seemed like, yes, I think. So that is one, that is one, you know, potential. But the thing that's interesting is when they see this, the B cells are actually gone. So it's not like, oh, look, here's a T cell, B cell conjugate. Like they, there's no B cell, you know, present in the tissue at the time that they, like it's happens after that. So that's interesting. Now the other thing like later in the paper when they talk about what could this be, that they do talk about is that, you know, you're going to also be re-infusing some of the patients own T cells. And it may just be like, hey, now you're re, you know, you've given them cytoxin and fluid air being. And now you're actually, you know, putting back some of the pathogenic T cells. So you're almost getting a little graft versus host is easy. Yeah, sort of, except. No, not really. Yeah, yeah. Yeah. Okay. So yeah, interesting. So, so most, you know, most common things that they saw were transient worsening of renal function, progenuria, transient skin rashes, and then musculoskeletal. So if you have bad lupus arthritis, like you would get a little flare of like a transient musculoskeletal flare. hopefully are.
So I thought that that was sort of interesting. So of the skin 19, so they had 19 patients with skin manifestations. So it was like an arithematous rash swelling of oral mucosa, mucocytus and one. There's one that had these cutaneous nodules on the hands, one who had worsening of digital ulcerations. And the median time for skin manifestations was like 19 days. So median time to see lycats start at all was about 10 median time for skin was about 19. Most of them did not need anything more than like a prednisone treatment. They did have a couple patients that had skin biopsies as interesting as this rheumatology paper. And they're like, and there was kind of like not much inflammation. It was nothing. But then when you actually reared what they said, they said, you know, three patients skin biopsies were performed. So they had one patient who had a biopsy day 30 after getting their car T cells. And they saw interface dermatitis infiltrating CD4 and CD8 T cells and then myeloid cells as well. They had another one that was taken on day 70. They just saw some like CD 123 positive myeloid cells, no B cells. And then another one that was taken on day 35. And they showed like CD4 and CD8 positive T cells and not B cells. So at the time of biopsy, there was like really like B cell depletion in the peripheral blood. And there were no serologic signs of lupus, like no double stranded DNA. That was negative CD3 and CD4 were were also normal. So you know, just interesting because I think like we will potentially start getting called for this. I think it's something for us to be aware of. And they had some good pictures. You know, one of oral ulceration. You know, they the manifestations were not necessarily that dramatic. It was sort of that like, you know, erythematous papules on the face. There was a couple pictures that were of patients who had like what looked like these particular lesions on the fingers. But you know, after prednisone treatment, they all seem to go away. They also have like a CT scan of the lungs. So I thought, you know, this is interesting. This is sort of like an emerging dermatitis and just something we should know about. Yeah, that's cool. Pat, any final comments for going to your first paper? No, I haven't seen any autoimmune CAR T patients. I've seen lots of hematologic, but I don't think I've seen any autoimmune people. What are the hematologic people get kind of a similar thing? It's it's really non-specific, pretty pretty heterogeneous. They get more cytokine release syndrome though, right? Like they can get in toxic. Like they made the point that lycats was not seen in the hematologic. Yeah, right because they treated patients. Yeah, right. It's a totally different process. They get at this neuro. There's like a specific neuro reaction with the CAR T cell hematologic patients. Yes, it is called immune effector cell associated neurotoxicity syndrome or ICANNs. Yeah. Yeah, okay. Yeah, it's just something different to be aware of. All right, Pat, and what do you got? All right, my first six pack pre-proof article accepted May of 2025 in the journal, "Ocula Surface." We're all reading it. You guys know it. It's by win. It's by win at all. They just did their swimsuit issue on the leader. It's by Yen, I'm sorry, it's by win at all. And it's title, Janice Kainase inhibitors and the treatment of refractory cicatrisin conjuction. Psychiatrizing conjunctivitis and pempagoid retrospective chart review performed at UT Southwestern Opthemology and Dermatology clinics. Between 2015 and 2024, patients had sickatrizing conjunctivitis. We're treated with a Jack inhibitor, had six months follow up. Number of patients in the cohort was 32. Most of the patients, 71.9 had only ocular disease. The rest had a combination of ocular plus another skin or mucosal surface. Ormucosa was involved most frequently. Most eyes had moderate to severe disease. With eight eyes having only mild disease and 16 eyes having end stage disease. Previously failed therapies listed at the bottom of table one. Micophinal eight was the most frequently used therapy or tuxamabnexpose frequent, but still fewer than half of patients, which that's surprising to me. I try and get all of the scarring pempagoid patients on or tuxamab just because like, you don't want scarring to progress. So be aggressive. It would have been helpful if the authors explained corticosteroid use in more depth like systemic corticosteroid. I just, like I didn't even know if all the patients were on systemic steroids. It was kind of confusing because one of the target is there was a complete remission and then complete remission off steroids, which one would assume they're all on steroids, but they didn't explicitly say that. So that was kind of hard to follow. So in any event, patient were placed on berry or tofa. It was about a 70 30 split. And they were followed for an average of 18.9 months, figure two shows two swimmer's plots. It's the same exact data. They just put it in a different order. So lots of different numbers in the results. I think kind of the takeaway points are, they summarize them nicely in the discussion, 33 out of 34 patients had improvement after six months, 43.8. So a little under half of the patients with clinical remission at 12 months therapy was discontinued in four patients because of adverse events infections. There was a TIA. There was a PE four of the patients that achieved clinical remission or better relapsed. That happens a lot in immunobulose disease, unfortunately. And over half of the patients had only a partial response. So Jack inhibitors seem promising. I'd rather use them than cyclophosphamide, which I kind of use in all my patients as well. I'm still probably going to use Rituximab for ocular Pemphagoid patients, but right. I mean, the difference would be maybe we start subbing in Jack inhibitors for the cytoxan. I. Is the one cyclotryl Pemphagoid patient I have who like, I don't even like when she comes in for skin check, I'm like, Hey, how are your eyes? Like her eye doctor has around Rituxin or whatever. Yeah. And it didn't like make her disease go away. Like so it's maybe that is do you think this will be second line after Rituxin? Well, so what I do with these patients is I start them off on a corticosteroids, moderate doses with the plan to taper over several months. I get them set up for a tux mabb and I start psych toxan right away. And where I see Jack inhibitors coming in is maybe instead of the cytoxan I'm using a Jack inhibitor. Eyes that had higher foster stages. So that's just like a grading, you know, scarring, no scarring mild scarring moderate scarring severe end stage scarring. So eyes that had higher foster stages didn't respond as well. I think that is intuitive lower foster stage. So the key is and it is whether we're talking about Jack inhibitors or not is initiating when once you see scarring jump on those patients be aggressive. Initiating the Jack inhibitor in this particular study. Those patients tend to do better. So it just reinforces the idea of ocular pempagoid needs to be diagnosed and treated aggressively. The biggest barriers is obtaining the medication at this point. You know, they had to they had to do prior authorizations. They got insurance to pay for it in a few patients. Patient assistance programs, which I don't quite understand how they did because a lot of times patient assistance programs from the companies. It has to be an FDA approved indication. So I don't know how they did that. And then they had overseas pharmacies, which that's so interesting. But yeah, I mean, you know, small study retrospective. I was talking to Steve Devlui, who's like on the editorial board for Jack, Chad case reports. And he was like, we pretty much have decided we're not taking anymore case reports about Jack Jack inhibitors working for X Y. Like they did they work for everything. You can if you're going to send in a case report. It's got to be that a Jack inhibitor didn't work. Yeah, interesting. It's just yeah, but these are I think sometimes helpful data for us to have right like we're not yet a Jack inhibitor, sycotritional pempagoid study. So, you know, right. This is like important to have these things. And it's our only kind of leverage with pay or sometimes so. That's right. Yeah, it's going to be interesting to see how well they work in in scleroderma. There was just a report of tofa for morphea. I haven't looked at it yet to see like you'd have that pretty bad morphea to like warrant tofa. But it's going to be interesting to see. Because I think of that as the other disease that just it sucks. We don't have anything good for. So that's a fibrosing like you know there it's not just an inflammatory disease right and like do you think that there's some effect of the Jack inhibitors on the fibrosing or on the actual scarring or do you think it's just the anti-inflammatory effect or I mean, so we know that fibroblasts have the I.O. 4 I.O. 13 receptors on them and whenever you do whenever you block those you down regulate those go through the Jack stat pathway. So yeah, I think I think that the Jack inhibitors I would bet that they have some effect on on fire.
and then Tim, because you treat a lot of these patients, is there any benefit to any sort of topical therapy early on, or is it like you just got to go systemic? - For scarring, no, like topical, and most of the good ophthalmologists know that. Like if they see scarring, you know, they usually have them on some sort of topical, but they know, I mean, they're sending them to me because they know they need systemic therapy. - Okay. - See, I'm sending-- - You've been early on, there's no benefit, I guess. - Matt, that-- - I don't know if they have it until they're scarring. - Yeah, Matt, you said the ophthalm gives-- Like, I'm blown away by that. The ophthalmologists don't want to give like, DAPSONE, they'll give PrednaZone, but you know, it's the oddest interactions because the patients come to me, they have nothing wrong with their skin, even oral mucosa, derms do. But they come in with eye disease, and I'm like, I don't-- I think you're better, you look better to me. Like, you need to see the eye doctor to evaluate, and then they call me, and they're like, we need to be more aggressive, and it's very weird. - Yeah, Ohio State has some, I think there's one particular ophthalmologist here who's like, that's this thing. - Okay. - Yeah. - So, and not that's not to say, like, "UPMC opthop people are terrible." They're really good. (laughing) Where they do a lot of benefit is, once we get the scarring quieted down, they do some pretty crazy, like, surgical procedures and flaps and things like that, to correct, and tropian, and scarring, it's pretty impressive. I don't know, like your eyes, are eye surgery? - They're gonna start asking you to do that next? - Maybe. - I'll do it. (laughing) - All right, let's move on to my-- I'm actually, I'm gonna sneak into here. One was pretty straightforward, and it just confirms kind of what I thought. So, it was a long-term, real world effectiveness of DePilomab versus Upatacidinib in early treatment responders with Atop of Dermatitis, results from the Central European Health Fund Registry. So, this is a registry out of Poland, and participating in the registry is not optional. So, if you are like a hospital that has the Polish national, whatever, you gotta, your people gotta go in this. So, at 200 and roughly 15, 215 people who finished 40 weeks of Rhinvoke and 220 people who finished 40 weeks of Dupy, and it was literally just, hey, from this date, the next 200 people who finished 40 weeks were gonna get 'em, and the next 200 people who finished 40 weeks of that when were gonna get 'em. So, not a randomized trial or anything like that, but good, good solid number of people. One of the big things I wanted to make sure of was that the people who went on Rhinvoke hadn't previously been on Dupixent, and they hadn't like five of, less than five of them had been on Dupixent previously. So, it wasn't like these were Dupixent non-responders. And the main takeaway was that the efficacy of Rhinvoke was better early. So, by 16 weeks, they were pretty equal. Other than whenever we look at easy 100, Rhinvoke had more people at easy 100, statistically significant, a week 16, a week 24, but by week 40, Dupix was statistically significantly better. For easy 75, easy 90, and Rhinvoke and Dupix were equal. And so, because the real question has been like, we knew that, because the data, you know, Ab, these have been pretty careful to make sure they're trials only go to 16 weeks so that we didn't know if Dupix was gonna catch up or not, but sort of the expectation was, but you didn't know, did it catch up all the way close or what? And so, this makes it certainly not a randomized trial or something like that. So, I'm not gonna sit here and say, well, this proves Dupix better in the long term, but it shows me that the drugs become extremely similar in the long term. And then the second one was another Rhinvoke one that was just very interesting. So, this was a 24-week study on Spain. I think they had, like, maybe 60-some patients in here, but the thing that was interesting right, so great Rhinvoke worked, just like it does and everybody else, the numbers were about the same. But what was really fascinating, they looked at diagnostic delay. And that is one of my, to me, that's one of, one of, if not the biggest unmet needs in the dermatitis world, is from the day somebody first shows up at a doctor and says, I'm gonna need you rash until somebody says, oh, that's a topic dermatitis. How long is it? So, their average diagnostic delay was four and a half years. And my, I think it's even longer because I, because I think there are a lot of people who never get the diagnosis of a topic dermatitis. You know, they just don't onset. They don't have any topic comorbidities. It's not flexural. And so, they're just called derma-specified forever. So, it was interesting. This was the first data I've ever seen on diagnostic delay. And then second, and this was even more interesting, the longer your diagnostic delay, the less efficacy the RINVOC had through 24 weeks. And so, you know, we know in alopecia riyata that the longer you have it, the less likely you are to respond. But we really haven't had any data on that for a topic dermat. And this suggests that the longer that diagnostic delay, at a minimum, the longer it takes to get the full effect of the drug. And that kind of makes sense because we do think of there as being the barrier function, even when your skin looks normal and feels normal, it's not biophysical parameters are not normal. And it would make sense that the longer it's inflamed and damaged, the longer it's going to take for it to recover, it could also be that, you know, the people with longer diagnostic delay had a different, means your a topic dermat is weird. Maybe it's not really a topic dermat, maybe it's something else. So, it's hard to fair it out exactly why. But two things there that were really interesting and that, you know, to me, help point even more towards, there are a lot of these people who just recall them dermat unspecified and then they're stuck getting nothing but topical and systemic steroids. And not only is the steroid, too, me a little amount, maybe causing some issues for them, it's also making their, potentially also making their disease more recalcitrant. Are you arguing that they're getting lots of topical steroids? And now there's like totally destroyed their barrier and they're unsalvageable. If I would don't know if they're unsaid, because this only went out to 24 weeks, I would, I'm wondering if it went out longer, if it would, you know, if it went out to 40 weeks or 52, if we would get there. But harder to salvage is what I would say at this point. So, do you think that like this late stage, later in life, atopic derm is the exact same disease immunologically as like the people who get it classic, flexural as kids? Like, are you like, it's just the same disease. One person got it at 50 and one person got it at 40. Think they're two different diseases. So, I think that they, I think that the final state of, and I, because my definition of atopic derm is inadequate barrier function to resist normal environmental stressors. And I think the difference is childhood onset atopic derm, you genetically don't have a barrier. And when that, you don't have an adequate barrier, when that happens early on, your immune system gets exposed to antigens in a different way. Transcutaneous rather than transpecosyl. And so then the disease takes a different course. I think the people who don't get it to their own adult, we know this, that genetically they're normal. They don't have the genetic stuff that the kids have. It is the acquired through long-term exposure to chemicals and clothing, air pollution, laundry detergent, bathing, your old life, all of this stuff. So, you end up in the same place with an adequate barrier. But I do, I think they were pathophysiologically different diseases because of the, you know, my bet would be you don't have as much of a systemic TH2 shift in the adults. But, but it, so what do I, I wish there was like two separate diagnoses I could make, like genetic atopic derm and acquired atopic derm, because I think they're different diseases. But they respond the same to therapy. And so from a practical perspective, we should just call them all atopic derm, because then it opens up the therapeutic toolbox. And the, and the first paper that you covered. And I mean, I'm, I favor Dupy over Oopa. But if I were to argue in Oopa's behalf, did they break down 15 milligram versus 30 milligram dose? They did, but it wasn't, like they didn't, so they, they were allowed. So basically the drug was used according to label. So the physician could increase and decrease and change the dose. However, they wanted to. My recollection is that the majority of people were on 30, but not all of them. But they could go to 30 if they wanted to. So it was, you know, quote unquote real world use. And that's an interesting challenge. We've got an article submitted, uh, Abro. So, uh, Subinco did a try, it actually did a real trial like that where, like, I was an investigator. And you just, you could talk about 100 or 200. You could switch anytime you wanted. Uh, and it gets really hard to report that data. Like how do you.
You know what I mean? We basically said like, okay, two-thirds of people stayed on whatever they were on the whole time and about both doses. If you started a hundred, there was one-third chance you were gonna bump into two. If you started two, there was one-third chance you were gonna bump into that one. But it's a tough thing to figure out how to report that data. All right, next study. Ferris, we got. So I have from Jamma Dermatology, Zhao at all. Ivar misitnib for moderate to severe atopic dermatitis and adults and adolescents. So phase three randomized clinical trial. I was not part of this one, but you know, always interesting. So what is Ivar misitnib? It's a highly selective oral Jack 1 inhibitor developed to treat atopic dermatitis. And so, you know, what does that mean? In vitro studies, they say shows a nine-fold greater selectivity for Jack 1 over Jack 2. Jack 2 is the kind of Jack that we like to avoid because it is what, you know, inhibiting it is what increases the root, that increases the risk of anemia and neutropenia. So 16-week double-blind placebo controlled study, two doses of Ivar misitnib for and 8 milligrams, about 112 per group, patients for 12 to 75, typical inclusion criteria for an atopic dermat study. BSA 10% or more, easy 16 or more IGA, three or more worst-ish numeric rating score of at least four. And the primary endpoint was an IGA of zero or one. And so what percentage of patients got that? And the four milligram group, 36% and the eight milligram group, 42% and in the placebo group, nine percent, easy 75, response, 54% and the four milligram group, eight, and the eight milligram group, it was 66% and it was 21% in the placebo group. So what was the mean? I like to kind of look at data sometimes like that. placebo adjusted, least square mean change and easy score. Basically, how many points did your easy score go down by I actually like a better fits percent, but it was like six points for the four milligram group and 6.8 for the eight milligram group. 44% had at least a four point reduction in their itch. Safety wise, they're all of the eight adverse events of special interest were serious infection. There was one case of a reseller, one case of sepsis in the four milligram group, one COVID-19 pneumonia and the placebo group. There were, let's see, other things that they saw, they saw typical kind of lab shifts that we see with Jack inhibitors, CBK elevations LDL, triglycerides and then decrease of plateslets and neutrophils relative to placebo transient and self limited. They saw acne and folliculitis, particularly in the high dose group at eight milligrams mouth ulcers. There was there were no mace events and no thrombo embolic events. So, you know, I thought it was interesting, you know, I'm not curious because I think you think about Jack inhibitors all day long. What do you think about this like relative to the other jacks that we have at our disposal and how to important is this Jack one selectivity. So, don't think it's important at all. So, Subinco is highly is more Jack one selective than this. Renvoque is about two thirds Jack one one third Jack two, tofaceted. It was primarily a Jack three inhibitor. So, and these numbers just they're they're top line number of how many people got. And IGA success or easy 75 success were almost identical to all the other Jack trials so far it's playing out that at least in efficacy terms. It doesn't seem to matter with what Jack you block like Jack one Jack two Jack three. We don't know about tick in a topic. Derm nobody's really studied it yet, but Jack one Jack two Jack three doesn't seem to matter. You seem to get the same efficacy and whether there's a safety benefit to only doing Jack one. We're probably going to find out because insight povo, which is their Jack one selective molecule that they're doing for H s they're pushing the dose a little bit higher than were used to in order to try and get more efficacy in H s. And so we'll see if that has a different looking safety profile you imagine the higher they push the seems so far it seems with all of the Jacks the higher you push the dose the more minute suppression you get. But mason vte who knows. Yeah, serious infections, the only ones that were there was two in the low dose. Iver group so in then you know it's interesting like there I mean this isn't a huge study but no me snow thrombone ball of events now when you put 12 year olds in your study that helps a lot too. Obviously it's a little you know versus like if you look at no adult population. So but just thought I put it out there at the people's radar another Jack and I would. Interesting. Alright, Pat and what do you got my second six pack was from the journal social science and medicine was titled public preferences for skin cancer prevention policy policies a discrete choice experiment in three European countries. It was by box spelled at all is available on you. How did you even find like did they come out with a swimsuit issue to and that was the. I can neither confirm or deny that I will neither confirm or no comment it's a veil it came across my little search thing that I have. You're okay. Okay. It's available online as of May 2025 the researchers wanted to see what sort of skin can the headline grabbed me I just kind of like yeah. It's going through the paper. I'm like what did I do the researchers wanted to see what sort of skin cancer prevention policies would be preferred by the general population of three countries spain. And other lands in Austria they did this through an online survey using what is called discrete choice experiment or respondents had to choose between two packages that had different policies matched with the effects and cost that the policies would have an example is given in figure one. And so if you look at it you know patients I'm sorry respondents would basically look and it was you know campaigns banning the sale of solar beds banning tanning beds a 30% price reduction in sunscreen free. Provide provision of sunscreen in public spaces and a free skin cancer detection app so like those were the options like these are the policies that we would institute. And then they would have theoretical like if this one decreased cases by 10% this one decreased deaths by 15. Here's how much it would cost. And you would just pick one of the two and then they would change everything and you would go through that 12 times so it's very like a statistically sort of Matthew driven way of this is what epidemiologists do. It would be a blast to hang out with the epidemiologist is what I took a lot of epidemiology tender. Yeah. Yes. Right. Slightly left swiping. Yeah. Exactly. It would be very well studied tender. They were really over 1000 respondents completed the surveys. The authors did a bunch of maths and that's when I realized this was a huge mistake. They're like tables with 50 numbers that have five decimal places. But you don't have to actually go through the tables because they sort of make these other graphs that put that data and clearly so figure two a basically shows it's a bar graph. Additional taxes that is the least favorite attribute and the most important like that that was kind of front and center that's where the emphasis was for these respondents. How much is this going to cost that was the same in all three countries. Table four shows what are called these MRS instruments. What is the it's marginal. Sorry. marginal rate of substitution. Yes. And so really what that is is it's a number and that's what patients say I would be will I would accept this much in taxes. For this particular product. So the top three measures in each country. For which respondents would accept higher taxes were information campaigns 30% reduction in sunscreen and a free skin cancer detection app. Countries differ on what they would accept the highest increase for Austria information campaigns. Netherlands and Spain. It was the 30% reduction in sunscreen price. Netherlands overall a little bit cheaper not to discharge Dutch people are Dutch listeners. But come on guys. Overall less willing to pay more in taxes for each of the measures. Bands on the sales of tanny beds and tanny bed prohibitions were the least favorite option in all three countries. I think that is kind of interesting. Given you look at what the Academy American Academy dermatology and how they've had those those campaigns and I just figure three shows mediums and means of that MRS estimates based on the reductions of new cases and deaths. I mean everything differs. But what I would stood out to me was the median. So like what most of the population feels. So it was like this panel B most of the popular.
population don't seem willing to accept higher taxes if deaths were reduced. Like if they said deaths were reduced by 10% Most of the population like the median you had these outliers because the means did change But for the median population they're like you reduce them by 10% I'll pay this if you if it's 25% I'm still like I still only want to pay what the 10% was if I was reading all these graphs right Figure four shows overall populations in all three countries did favor policy actions It went up so they tested they asked them that question do you favor government policies that would reduce skin cancers and Before they did this discrete choice experiment majority of each country said yes, we do After it it all it went up in all three countries So you know overall if you're into the policy stuff emphasis should be from if you took this Paper at face value emphasis should be information campaigns lowering the cost of sunscreens Minimizing the amount of taxes that would have to be levied to implement these policies or don't increase taxes at all and Don't go after the tanning booth. That's the least favored sort of policy When you look at the populations So interesting you think that'd be the cheapest thing is to just say No more like to ban Solariums are like the tanning beds, right? Yeah, I mean that's like what we're most of our advocacy has focused Through a D through like state organizations. It's not I mean It's really been on like not allowing minors to tan People under 18 right. It's like why we don't let people under 18 get tattoos, right? Like you don't make It's almost like a psych a lot like people don't People like being said hey, uh, we encourage you to do these things that will help skin cancer I just reflexively people it seems like they don't like being told what not to do Um, you know, uh, though a band it's not like that's free, right? If you have to institute a band and police it and regulate it It's gonna cost a little bit money, right? And that you know, there's this thing called the sun What? May make banning tanning. It's kind of silly. Yeah, so I don't know I thought it was a cool paper. I was gonna be on that that was gonna be my campaign gonna run for a D present on banning fun Yeah, that was a Simpson's episode Mr. Burns put up a big canopy over the whole city I had I had two main thoughts in this thing number one I would love to have known how they chose the countries Like because I do think it was a good spread. I mean, I think of it is like when I think of Spain I think of is kind of laid back kind of lazy-ish people Ciescestas and all that when I took when I think about uh The Dutch I think about like very libero a let's smoke weed. Let's have a red light district Woo, and then whenever I think about the Austrians they're just like the Germans so very like uptight It's follow the rules and let's have rules and the whole that like if that's why they chose these three countries Was to try and get like a spectrum of stuff I like you've ascended half of Europe and one yeah, right. Let's keep going Yeah, let's maybe move it eastern. What do you say about the Indians? But would they have the other thing? I thought was that these people discrete choice experiments are always weird to me because right the to to get sunscreen to be 30% less They basically the mean taxes people were willing to pay with 70 dollars a year Just spend more just you're gonna You're there's no way you're gonna save 70 if you're gonna pay 70 bucks it just buy the sunscreen at the price It's at now Yeah, that right it was like we'll make it cheaper, but your taxes are gonna be higher. Well yeah, right Just pay don't change my taxes at all and I'll pay for that more expensive sunscreen Right you'd you'd I did the math and you'd have to buy like $600 a year worth of sunscreen before it became like economically beneficial To have to tax yeah if if you were asking me I would be like I would accept zero dollars in a tax increase to make something cheaper I would just don't tax in it all That you're like you're spreading that Yeah, that's it right To help in the open the less I'm I'm in this for me okay on yeah, I would I would pay a little To if they put free sunscreen in all the public places so that when I got there and we're like oh damn I forgot to bring sunscreen like there would be some sunscreen at the park or the beach or whatever I was surprised that that one wasn't higher. Yeah, yeah, yeah, it's weird. It's a neat Yeah, buddy. Yeah, I was in I think I was very interesting I was I was not expecting that banning that the tanning beds was gonna be like the least favor because yeah Well, I feel like most people don't go to a tanning bed. So why that why would you care like yeah go ahead ban it whatever I don't care yeah weird yeah, yeah, all right. Let's let's go out of my last one which is uh A little bit kind of a about an interesting thing of what's happening in the world So these were the most recent North American contact dermatitis Group results in North American contact dermatitis group patch test results 2021 And the most interesting thing in this every year is like what's going up and what's going down because it's it we don't really actually have any good data on How often patch tests are relevant right? So the the vast majority of people when you find a relevant positive patch test They don't get better right that's the what the data is so it's it's hard to know like Okay, these actually meaningful or not but the number of people with a positive test that's a meaningful thing So you can compare is it going up or down and the main takeaways were this all of the metals nickel cobalt golden chrome 8 from 2020 2021 and one went up uh, so that suggests there's more metal sensitization going on maybe that's more tanning or not more tanning more piercing sorry Benz alconium chloride went up so that is suggestive of more hand sanitizer use because Benz alconium chloride is one of the ingredients in hand sanitizer It's also used some in as a preservative in some products uh, and then at the other two preservatives that were interesting so brunel Paul went up Which is a vaguely from out of high related one but not much not very from out of high related benzoates went up Those are a replacement for for amount of hide And isothia zolanone and so it it leads to the because then isothia zolanones and for amount of hide both went down And so what's happening is they're taking the isothia zolanones and the for amount of hide out of products and putting in Benz alconium chloride so allergy to those is going up and that is the same thing that happened with isothia zolanones They tried to get rid of from out of high by adding this phyzolylonus and it turned out oh my god I suppose all the knowns are even worse than from out of hide So we're we're seeing a little bit of that same phenomenon happening the other ones that were interesting uh, so three different non sulfate surfactants So olyneopropyl olyopropylum dip- olyp- o- p- d- m dimethylamine apropylamine and ammonium per- Amid oamine which are all markers for uh, bettain allergy went up Uh, and so that suggests that the whole thing with sulfate free products is Causing an increase in allergy to other surfactants because companies want to put sulfate free on the label And they got to put something else in that makes it lather up and then the last ones Some fragrances went up some fragrances went down again. That's just expected because Like what's popular in a fragrance changes. So like you know perfumes that people are buying now don't smell like your grandma's perfume And so like summer going up summer going down that's expected But then the other one that was very interesting we just started patch testing widely to ammonium per sulfate a few years ago and it More than double almost double so one from 1.9 percent positive patch system 3.4 percent And that is believed to be Due to people using hot tubs more so hot because the about the only place people really get exposed to per sulfates It is the shock treatment Used in hot tubs and there's two main ways you can shock you can use like a ton of chlorine Or you can use per sulfates when you use a ton of chlorine like it makes it smell more chemically And you got to stay out of it for like a day when you use the per sulfates. It doesn't smell chemically Uh, and you can get back in it quicker And so it looks like the per sulfate allergy is rising because of both increased hot tub used potentially somewhat related to the pandemic and People just switching from chlorine to the per sulfates the the one pearl I would give from here is if you get somebody gets a new one set widespread sponge germ Assume if they have a hot tub and if they do they need to stay out of the hot tub for like a couple months if their rash gets better They get back in the hot tub And you have then confirmed that they have That's this per sulfate allergy and then they have to switch to sulfate free per sulfate free shock for their hot tub Uh, that's one of the most commonly missed causes of widespread dermatitis is per sulfate allergy in hot tubs Thoughts from you guys on uh, it's just it's interesting what's changing is the biggest thing that is
that I always find with this. - All right, it's interesting. That's good to know what's changing. How about the one that I think I mentioned a few episodes ago, propolis from-- - Yes. - What's that doing? - So it dropped precipitously, 'cause it was like ludicrously high. It was like a 10%. And that was like there was like no way that has to be false positives. And they think it was that the allergen that was being used was too strong or something weird about the allergen. So propolis went from 8.7% down to 2.2%. For our listeners, propolis is an allergen in beeswax. And it's one of the things. If you see somebody you think has a allergic contact or a dermatitis of the lips, you wanna make sure that they use nothing but either Vaseline or Serovie healing weightment. The two things you do there, you switch to nothing, but those two things on your lips and then you switch to a flavor-free toothpaste because those are the-- That's almost all allergy for lips or those three things flavor in toothpaste. Favorite toothpaste for that, by the way, is Cleor, CLE, URE, and then making sure that you don't use anything except for Serovie healing weightment or plain Vaseline on your lips. Is the sodium laurel-free, sulfate, SLS-free toothpaste? Is that, I think, for lip derm or not? - No. - Okay. - So SLS, - Sodium laurel sulfate. - Yeah, nobody's allergic to SLS. It can be irritating. So there are some people who get like irritate, like they'll get oral ulcers or oral pain from SLS, but it doesn't cause allergic contact dermatitis on your lips. - Okay. - That I must have been thinking of the oral. - Yes. - All of their stuff, yeah. - Yeah, but there is-- There is some suspicion that eosinophilic esophageitis may be partially caused by sodium laurel sulfate in toothpaste because now whenever you brush your teeth with sodium laurel sulfate, you swallow some of it. And so now you're getting the sodium laurel sulfate that's breaking down the protective lining of your esophagus. And that makes you susceptible 'cause something happened, right? Eosinophagositis didn't exist when we were medical students. - I thought we have due pixen that we need to put other degrees for-- - That's what they're diagnosing it. We all have. - It's like restless leg syndrome or whatever, but like never used to be a thing until we had a drug for it. - So we had a drug then, it's the thing. - Those eczema of eurosophagus, all right? - Yes, that's how I think of eocenema of eosophagus or asthma of eurosophagus, you can think of it that way too. But yeah, that's what's the hot new thing in the contact nerve world where these results. And it's definitely interesting. The immunompersolvates the main clinical probe take away from the whole thing. - Good, when I think hot, I think the patch testing contact dermatitis world, so that's good, thank you. - All right, it's popular as the swimsuit edition of ocular surface. - Exactly. - You can't hear the picture of the eye. You can't see the suit, but we promised they're wearing one. - They're wearing one. All right, well that was a great six pack episode. I want to thank everybody for joining us. If you've got questions, comments, topics, things which cover on the show, shoot us an email at
[email protected]. We hope you learned a few things, but black ones are twice, and mostly we're hoping you're planning to join us next week. Until then, I'm Matt Cyrus. - I'm Tim Patton. - And I'm Laura Ferris, and we are Dermsend Drugs. (upbeat music)
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