Breaking Dermatology Literature: A Probiotic for AD, A JAK Inhibitor for Pemphigoid & IL-23 Inhibitors for Guttate Psoriasis

[music] Welcome to season two at Derms on Drugs, a video podcast brought to you by Scholars in Medicine, the best educational platform in dermatology and provided are no cost to medical providers. Derms on Drugs is where cutting-edge dermi, it's in our Miss Comedy. I'm Matt Zyres in each week. I'm joined by residency buddies, doctors, law affairs, and Tim Patton to use our 60 years of combined derm experience to discuss, debate, and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of dermatology and you'll actually have fun listening. New episodes drop every Friday on Scholars in Medicine, Apple Podcasts, Spotify, and other major podcast platforms. And as a reminder, the video component has some of the key figures and tables from the articles we talk about every week. So this week, you're in for a special treat. We've got another one of our patented six-pack episodes where we are going to talk about the things that have grabbed this as most interesting in the literature recently. A bit of a "po-per-ree" if you might say, "Dr. Ferris, go ahead and get us started. What do you got?" All right, so I'm going to start off with something about psoriasis. And just by the way, after that, all of our listeners know how much paton and Ferris roll their eyes while I'm doing the intro. All right. I think we watch that's another reason to watch the video portion so you can actually really appreciate that and it's full glory. Okay, so speaking of glory, this is in the unproved glory straight out of the JAD. So the paper that I picked was "Sustained Remission of Gut Tate Psoriasis Flares" with short-term ILE23 Inhibition, a case series by Hotelin at all. So case series, nine patients who had flaring guttate psoriasis. So these were patients. Two of them had a history of plaque type psoriasis. The other seven did not. And eight of the nine had been tested for antistructalis and otiters and eight and all of them happened to be positive. So just to give you a flavor of who's in there, one of the plaque type psoriasis patients was actually on Otezla when they had their flare. So all these patients were started on SkyRizzi. On average about two months into their flare, sometimes it was as quick the earliest was started two weeks in, sometimes as late as six months. Most of them were also using topical steroid. So how do these patients do? So all nine of them went into remission after just two or three shots of SkyRizzi. And only one occurred and that was 16 months later and quite unfortunately after another strep infection. For everyone else, remission was pretty impressive. So they were duration of follow-up was like 11 months off drug and people stayed in remission. So why is this interesting if you are a SkyRizzi ILE23 clinical trials aficionado? You might have heard of the knockouts study. If you presented at AAD, if you go to HCP Live type things, you can see Andy Blow belt talking about it. So this was a randomized phase two trial where they basically said what if you have patients with psoriasis and you give them early high dose SkyRizzi. So 300 or 600 milligrams per dose at week 0, 4 and 16. And what they found was that patients had this high response rate when they looked in their skin, they knocked out their tissue resonant memory T cells. And so they theorized that ILE23 is important for knocking out memory T cells in the skin and maybe we could actually knock out psoriasis. So I thought this was interesting. It makes me think maybe if you're going to pick a biologic to hit a new guttate psoriasis patient with go with SkyRizzi or an ILE23 inhibitor, mechanism kind of makes sense. And maybe this is going to change how we think about treating psoriasis like we'd be starting with ILE23s. You know, these are like it's a proof of concept that sort of hypothesis generating it's not a randomized clinical trial, but I thought something helpful. All right, two quick questions here, Ferris. Number one, do you check and we've talked about this before in terms of drugs, but guttates, psoriasis is coming. Do you check an ASO tighter and all of your guttates, psoriasis people? Do you just put them on some amoxicillin or penicillin or do you not? Do you do neither? Yeah, I mean, if they have evidence of strap infection, like I have a strap, I have a really sore throat, I will get them tested. I don't test for the antibodies. And I will of course treat anything that is true strap. I don't proflactically test. I do feel like it's rare that I get the brand new guttates psoriasis patients, but I don't have about you guys. Patton, I don't chase symptoms, not I don't randomly order the antibody, you know, take the tighter. So Ferris, now technically, this is off-label use of skyreasy corrected is only approved for FDA approved for the treatment of guttates, psoriasis in these people. And these people. And the proflact type psoriasis and psoriatic arthritis, but we love off-label treatments on terms on drugs. So I think I would try and get this covered in insurance would say no, and they'd say you have to do this and I would do that. And then I would say that didn't work. And then like guttates, psoriasis would go away. And then I would get the sky-rizzy approved and they'd be like, I that's all gone now. Then you'd have it in your refrigerator and you could use it in my experience. Yeah, I do have a lot of samples. Yeah, don't tell anyone. Okay. I know. That's just between us. We know three. So so interest. So two or three two or three doses of skyreasy and their guttates, psoriasis was cured at least for the short term. Until they got strapped again. But yes, until they got strapped again. Okay. Well, that's cool. That's that that's a good one. Ferris. All right. That's better than your usual like smart person stuff. I'm never going to see in clinic. That's real shade right there. Yeah. As the kids say. I think it's probably shaded. Ferris. All right. Pat, what do you got? All right. I did an article from the June 2025 issue of the journal of the European Academy of Dermatology and Veneriology titled digital der Moscape follow up for acquired longitudinal millennium, NICIA by Moscarella et al. Some quick facts about nail unit melanoma for our listeners that accounts for one to three percent of all melanoma's worldwide. Absolute incidents is actually the same across all races. There's a higher relative rate for non Caucasian populations. More often affects the fingers and the toes. Most often affected digit. You guys got a guess. Thumb. Thumb. That's a thumb. There's actually a different ADC mnemonic for nail unit melanoma. So for A, they say age, it's peak incidence between the fifth and seventh. African Americans, Asians, Native Americans, higher relative rate. B is brown, black, discoloration, breath of three millimeters, variegated B borders. C is change in nail band or lack of change in nail morphology despite treatment. If you think it's fungus and you treat it for fungus and the pigment doesn't go away, then you start to think about melanoma. The D is the digit affected thumb. Number one, number two, index finger, number three, great toe. E is extension of pigment. That's Hutchinson sign. F is family or personal history of melanoma. A little bit of a different mnemonic I thought was always kind of cool. There's also a Domatoscopic criteria for early nail unit melanoma involvement of more than two thirds of the nail, brown, black, background, blurred borders, irregular lines, granular pigmentation and or nail dystrophy. Usually presents as longitudinal melanica, which is the most challenging aspect of nail unit melanoma because way more often than not, it is benign. Longitudinal melanica is benign. And performing a biopsy isn't like performing a biopsy pigment elusions. Technically hard to do. We're comparatively damaged in the nail. It's just like, I don't want to do this. So the goal of this paper was to see if there were any Domatoscopic changes that could be used to determine which longitudinal melanica could be followed clinically, which changes should prompt a biopsy, multi-center retrospective study. Patients had a pigmented band and were followed for at least one year and eventually had a biopsy of the band performed. Well, some of them did. So final analysis included 62 bands, 56 benign bands and 6 malignant bands. 27 biopsies were performed. That's what picked up the six melanomas. So, you know, most lesions, again, like we're benign. All of the six lesions that were biopsy, were malignant melanoma in C2. First table looked at the baseline characteristics of the bands. So they didn't biopsy all 56. So the 27 biopsies. Yeah. So they're 27 biopsies were done. Seven biopsies. So 26, seven biopsies were malignant. So it's possible. Wait, did you, I'm sorry, did you say seven biopsies total? 27. 27. Okay. So 21 benign biopsies. Okay. So that's good. I thought they biopsy like none of the benign ones, which I was like, well, how do they know they were benign, but okay. - I mean, they still don't know that, right? - Yeah, so they're saying, in their benign analysis, they're including things that weren't biopsy, so who knows? But first table looked at baseline characteristics. So this was kind of a, what can I use at baseline that would, that differentiates malignant from benign and there was nothing, right? So with of the band, color, granular pigmentation, irregularity, Hutchinson sign, nail dystrophy, most statistically significant differences between the two groups. After a median follow up as 17 months, 27 bands underwent biopsy, six melanomas all in sight too. What dermatoscopic changes occurred more often in the melanomas? If you had an increase in the number of colors, appearance of granular pigmentation and an increased intensity of pigmentation and they have some examples of it, we can put those up on the podcast. Those three things, again, increase in number of colors, appearance of granular pigmentation and an increased intensity of pigmentation, statistically significantly different between benign and malignant legions. Enlargement occurred in 50% of melanomas and only 23% of benign lesions, but that wasn't statistically significant. So that alone didn't help you. Like I said, they have some photos there. My takeaway is that if you're not really sure if longitude, malignant, and Nikki is benign or not, it's reasonable to take a dermatoscopic image, have the patients come back three to six months, compare baseline follow up dermatoscopic images. You see any of those changes that they mentioned, go ahead do the biopsy. You know, I think most of us have dermatoscopes capturing images can be a little bit tricky, but it's not like two technically challenging. You can get pretty good dermatoscopic images with your cell phone and a dermatoscope. If the baseline and follow up images are stable, I think it's okay to clinically follow. Some interesting points about the paper were raised in a letter to the editor about the article. One point raised, two lesions were diagnosed around five years after initial presentation. Another lesion was stable for one to two years before changes were noticed. So how long do you need to keep coming back? You know, I used to think like, oh, come back in three months, nothing changed. This is therefore not melanoma, but it did take longer for one of the particular lesions to undergo that change. So like what do we tell patients two years? Is your cut off? No changes in two years? I, you know, just kind of, I think I will definitely be doing this. It'd be nice to have a baseline difference where you could say because of these features. Half of the melanoma is involved less than one third of the nail plate. So over reliance on bandwidth should be discouraged. Big drawback to the study was all a bunch of weight at Italian people. You know, so skin of color, it would have been nice to see if they have similar sort of things that you can follow that would make you think more about biopsy to rely on melanoma. All right. So do you think, so first increase in the number of colors, I don't know if that's, that's like a pretty, so what did, like, is that like different? Yes, I don't know. It's objective on like dermoscopy. And again, they have photos of all these. It's not like, oh, maybe that increase. Like it's with photographic monitoring. It's like, so, you know, the examples they gave, you look at the baseline, it's like, I three, there's kind of three little medium brown lines that are there. And then, in one example, where the patient didn't come back for five years, which was great. They missed all their appointments, but came back in five years. And, you know, now you had that medium brown and some like brown and some dark brown. And, you know, it's like how many different colors were there at baseline? How many different colors were there on follow up? Yeah, fine, a little bit subjective, but not terribly so, right? And I mean, like, that's the beauty of having the photos. You can go, all right, that's like change. That's, you know, you're not trying to say, well, there was only light brown, but now there's light and dark and medium brown. Like, you know, trying to do it descriptively would be hard, but with photos, I think it's doable. That's, I photograph these and that's what I do. I mean, if I know it's melanoma, I biopsy it, but I photograph them because it is kind of morbid to get an L biopsy and I hate doing them. It's just hard to reason. I mean, technically hard. I've been doing it for how many years. I mean, the problem is we don't do it a lot. So I just don't have that same level of surgical confidence going in there. Yeah. Yeah. And then the other thing I thought was interesting is that, you know, like, we all see pigmented nail bands that were like, that's fine. You don't take a photo. None of those would have made the study, right? They only did it in cases where they had at least two photos and some clinical follow-up. So if you, they're not looking at the ones that we just dismissed outright. So these are sort of the more challenging ones. I would say, when I look at the pictures in this, the two that were melanomas that they took pictures of or at least melanomas in situ, like the baseline pictures, maybe I would have, maybe I wouldn't have, but like the follow-up one where they did the biopsy, both of those, I'm like, yeah, I would have biopsy that. That would be dramatically different. Yeah. I wouldn't need the baseline to be like, that one's pretty scary. Like, whereas the normal ones look pretty normal. Like, I just, I'm not, this didn't convince me that you need, the pictures didn't convince me that you need the, your microscopy. So you're saying, if you saw them at that second follow-up, that would be enough. Like, I'm doing the biopsy. Well, at least I'm sending them to somebody to do a biopsy or, you know, they're not your run of the male longitude in omelana nichias. Is what, is it, I guess what I would say? But we're not seeing every photo in this study, right? Yeah. We're not seeing every one of them and you're seeing the ones that are the best quality photo and maybe the best examples and so. And I think the point is that with the melanomas, when you look at the baseline, I don't think I would have biopsy, I mean, it was only the two examples that I wouldn't have biopsy either of those at the baseline. One of the whole point. Yeah, definitely wouldn't have biopsy figure three, figure two, maybe, but probably not. Yeah. So I think that's the point is this is probably the best way to manage these patients. It's fine. Less, right. You think, oh, this is really bad at that first visit. Right. So again, how long did you guys say you would probably separate them by a year, six months? Six months for me. That's usually what I say. And I mean, I always say to the patient, like, I oftentimes will say, like, take a picture. I'll take it with your phone. And if it changes, call me. Like, I'll get you in, but I can't ever remember anybody ever being like, oh, I swear it's changing. And then having them come back. I say six months. Yeah, that's a good, I have no idea. I think I probably have said three. Okay. Okay. The other like little pearl for nail unit melanoma is that there is an association with trauma and developing melanoma in that nail. So like, I had a patient who's like, oh, this is my nail, but it only looks like this because my bird bit it. And I was like, that's kind of crazy. That's not true. But then it actually, when I read up on it, there is actually an association. There's a higher risk of developing, or what, maybe that's not, that's too strong. There's an association between trauma to the nail and subsequent nail unit melanoma. So keep that in mind. So basically, it's if they say trauma, don't automatically be like, but yeah, cause, yeah. And I think I remember that, but the big thing with trauma is how long ago did it happen? So are you looking at blood or are you looking at pigment? Which usually it's pretty easy to tell. So a week ago, I'm going to think it's blood. But you know, if it was a couple years ago, just, you know, don't, don't do what I didn't dismiss it outright as not being associated cause there actually is the association. Okay. So I say Bob Marley never worried about his melanoma cause he was like, I injured that plane soccer. I remember. Yeah. I, it was Bob Marley was not the person I told that to. I just want to put that out there. Good. Yeah. Good for you, Ferris. You haven't been practicing that long, I guess. Yeah. Good for you. All right. So let's jump into mine. And as listeners from our last episode may recall, I am now doing a little something different for our six packs. And I'm going to be doing a little popery of my own of like three very quick hit or articles. Cause I'm kind of a believer if I can't summarize the article in like 15 to 30 seconds, it probably was too complicated to be clinically useful. So number one, if you could actually summarize anything in 15 seconds, I will be amazed. And I'll also point out we never happened. Yeah. You are from 12 or 14. So let's see. Let's go. Give it a whirl. So first, this was an article from a journal European Academy of Dermatology, Medinariology, efficacy and safety. So first, my first three or a topic dermatitis focused efficacy and safety of lebrachism, ab and a topic dermatitis over 24 weeks in analysis from the bio rep registry. Here is what was interesting here. They looked at people who are bio naive versus people who had failed dupe or people who had failed jack had an inadequate response to one of those. And those people still did well, but they did not do as well as people who had not previously failed one of the other two drugs. So the, and one of the interesting things, if we look at a low endpoint like easy 50, then it didn't seem to make much of a difference. But if we got up to things like easy 75 or easy 90, then it was a bigger difference of that the people who previously failed dupe or or a jack didn't do as well. They may have caught up some at a longer follow up point, we 24, but look like there was a lot of dropouts so hard to know. But basically confirms for us kind of what, you know, you would expect that people who fail one systemic agent are a little more recalcitrant to, you know, something else that does something similar. You know, and anything, any comments from the two of you on this one? Well, fits with every other psoriasis or whatever type study. Yes, you're selecting for patients with refractory, harder to treat disease. Yeah, the response and naive individuals. And it is interesting. We do have some data that suggests that inadequate dupe responders do not have a reduced response to jacks. So that, which kind of makes some sense because if you didn't respond to dupe, maybe it was a different pathway than I, all 13 and jacks hit a bunch of pathways. So it does make some sense to me that though now that if I've got somebody who failed dupe, I'm probably less likely to go to trailer or library than I am to go to a jack or to Nemo. And that again fits, we don't have a ton of data for that, but it kind of fits with the experience for psoriasis. All right, number two for me. So as lots of people may know, I am, well, let's, I'm a kind of believer that the conjunctivitis with dupe and other I/O 13 inhibitors, there's some belief that maybe it's an immune shift, some belief that it's more the goblet cells, I believe more the goblet cell hypothesis, but the interesting thing here, large series of people who got it. And again, no real easily identifiable risk factors, but the big thing was this was people who, with dupe got it earlier, I'm sorry, got it later than people who got it on trailer, but it was probably worse than the people who got dupe because more of them, so a quarter of the dupe patients ended up decying because of it compared to 15% of the trailer patients who got it, you know, hard to know if that's really meaningful. But the most interesting thing was that they had a bunch of people who switched from dupe to trailer and a few people who switched from trailer to dupe and so even some people who switched from dupe to lebry or trailer to lebry, and no matter what, every single patient improved some. So the conjunctivitis was not as bad after they switched drugs. Maybe that was just, you know, tincture of time, but that was interesting. So if you do get conjunctivitis on an aisle 13 inhibitor switching to another aisle 13, if patients are like doing great, but as conjunctivitis, it tells me it does make some sense and reasonableness to try switching to a different aisle 13. So they'll probably continue to do well and there's a good chance that conjunctivitis will improve but it's hard to understand why that would happen. You know, that's the kind of takeaway there. Are there huge differences in the percentages between the 413 combo like dupe versus just the 13 blockers and the percentage of patients with conjunctivitis? - It's maybe a hair more common in dupe, but that's not like we don't really know because it's hard to write the dupe patients. The baseline dupe patients were so different from the patients in any other atopic dermatitis trial. So it's, we don't know. His is the big takeaway. And then number three was a new probiotic study that literally, why don't we say literally, if almost literally knocked my socks off. So, - Figuratively. - Title of this study, transforming atopic dermatitis management, probiotics is a game changer in immune modulation, a double blind placebo clinical trial. This was out of Italy, well done study, not a huge number of patients in it, but I think there were like 60 patients, roughly 80 patients in here. So randomized double blind placebo control, they were allowed to use topical steroids. It was nuts, how well this worked. I mean, just kind of nuts. So the decrease in the score add and these objective measures was like big. Like big, big. So it was really an interesting thing. Let me find the exact numbers here. So the exact numbers. So there was in the score add, the people who got the probiotic had an average decrease of roughly 25 and the people who got the placebo had a decrease of five points. Even more telling easy scores, the people who got the drug had a mean reduction of 13.7 points, not the drug, the probiotic, the people who got the placebo got a mean reduction in easy score of 3.1. And these were patients who, you know, the baseline easy scores were in the low 20s, so 23, 24. And so these were like clinical trial severity patients and they got a lot better on this probiotic. Now with probiotics, you gotta talk about the specific probiotic. And so this was a probiotic that is available in Italy, but it is specifically available in the US. It's called Vis Biome, VIS BIOME. And it costs about 70 bucks a month. Now the probiotic that I have always-- - Oral probiotic. - And oral probiotic. - With some of those topical, okay. - Nope, nope, nope, take it. - Vis Biome. - Vis Biome, VIS BIOME, and it's marketed more for GI disease. But 70 bucks a month. So expensive but not terrible for something that's got really strong data. Now the probiotic I've always recommended is called now probiotic 10. And it has seven, so there's eight strains in this Vis BIOME. There's eight species in it. The now probiotic has seven of the eight species. But that doesn't mean that it's definitely the-- You know, it doesn't-- I can't sit here and say, well, now probiotic works just as well. But if the $70 cost is an issue, then the now probiotic is like $8 or $9 a month. I would say I haven't seen this kind of a result with now probiotic. I wouldn't have said it was gonna be the big of a difference. But this Vis Biome randomized double blind procedure but could try to use it with topical steroids. A very reasonable thing now in my mind to offer to people who really don't want to do a drug or do it together with a drug. 'Cause we know that probiotics really have a lot of immuno modulating effects, thoughts, anything that really-- What do you think? I mean, I love the idea of it working. I do think like microbiome probably is-- I used to kind of think it was baloney, but now I think it probably does matter for a lot of diseases. So yeah, I mean people would love that. So how do you buy this stuff? Is it like you got to order it online? - You got to order it online. This Vis Biome, again, the IASB, BIOME. - They fund the study? - I don't know. I looked through the whole thing. I couldn't find-- - It's just-- - It's not believable, right? I mean, I'm not saying, oh, this, it's just that atopic dermatology is so hard to treat. We didn't know what to do before we got these Dupy and the Trailo and the Jack inhibitors and all those guys. And now we're supposed to believe that, oh yeah, this probiotic. Totally, like, totally make your eighth. It's, this is one of those, I would have to see it in like 10 patients before I'd be really convinced that yes, this actually works. - And it was randomized, right? It was randomized, it blinded. Randomized double blind placebo controlled. Like-- - Yeah, which I mean, like, what did they make up the data? I don't believe they did that. - And the steroid, the steroid was like, investigators choice, patients choice, or was it like, it wasn't like the microbiome group got clobatus all and then the other group got hydrocortisone. - No, no, no, the two steroids that they used were either hydrocortisone butyrate or mometozone. Those were the two possibilities. And the other thing that I don't, I'm looking to see if I don't remember being able to find it, 60 days. So they gave this two months. So totally a reasonable thing to do. If you've got somebody who doesn't wanna do a drug, or if you wanna try and save money, but even for your mild atopic derm patients, this now makes tons of sense. But it was, it's hard to believe. But, you know, there's now a lot of data around the basic science of probiotics in atopic dermatitis. Like a lot of data around it. And now this really supports that the right probiotic seems like it could make a huge difference. Let's move on to our next study, Ferris, where you got? - I have red light PDT with 10% ALA gel for superficial basal cell carcinomas, a randomized vehicle control double blind, multi center phase three study, todge, slushing her at all. Okay, so this study looked at 10% ALA gel and red. red light PDT and 187 patients randomized for to one to either get the ALA or vehicle placebo. So I kind of like it. You get actually randomized to, is this ALA or not? Multi-center study. So this is like legit study design. Everybody had biopsy proven treatment, naive superficial BCC, mostly tronkin extremities. I do want to say the title is a little, they're kind of lying in the title, right? So maybe they tried for this to be double blinded, but like people knew which one they got, right? It doesn't hurt more. Yeah. Because if you get the ALA, it hurts, and if you didn't get the ALA, it didn't hurt. So what really double blinded it? I probably want to call this. But you can have, you can have like, okay, it's at least single blinded. Yes. Okay. So patients got two cycles of PDT. So a cycle is two PDT sessions a week or two apart. And then the target lesion was surgically excised at 12 weeks. So it wasn't like, say you have histology. So what were the results? Clinical clearance after the last PDT cycle was 83% with the ALA gel versus 21% with vehicle. Estilage clearance, 76% versus 19%. So that's significant. And the other reason why I like that is we all know like a lot of BCCs just go way after biopsym. So there's studies where you don't have a control arm and it's like, oh, look, we treated it. And like, we have a curate at 90%. I'm like, well, what was your curate with biopsy? So now we know the curate with biopsy wasn't like, it wasn't just a biopsy response. And then composite endpoint, which is clinical and histologic clearance, 66% in the ALA arm. 89% of patients in the ALA treated arm had the investigator rate. It is very good or good cause mesis. 95% of patients said they do it again. It was the typical side effects of like, you know, local reactions, redness, parietus pain. And the mean pain score was four out of 10. So, you know, how does this stack up to the other modalities we have? Surgical excision, you know, 95 to 99% five year recurrence freeze survival or recurrence freeze, I guess survival is still the word. And you know, but more scar and most 99% curate, you know, amicwamod, 5FU 80 to 85%. So, you know, I thought this was interesting. It was nice to have sort of a more rigorous controlled study. So is it revolutionized what we're going to do? No. But, you know, I thought it was interesting. It's a name, you know, it's an option you could give to patients. Now, I would still argue, like EDNC is kind of up there with that curate and is a one and done thing, although maybe cosmetically not quite as not as effective. So the big benefits is the big thing here is you're getting a, I take away a lower cure rate than say EDNC or surgery in exchange for a better cosmetic outcome if you cure it. If you were to compare it to say amicwamod, you're getting less, you know, time of, you know, having the wound and all that kind of stuff. You could treat multiple, right? Like a lot of times people have like, oh, they've got a bunch of superficial BCCs on their back. So you could imagine like you could treat multiple lesions at once and be done. Not that you can't do that with EDNC, but, you know, okay. All right. What do you think you're going to start? I thought this was terrible. I thought this was like just, I think this is a bad treatment. I think it's inconvenient for the patient. I think they tried to make it sound as good as they possibly could because it was funded by the company that either makes ALA or makes the like unit or maybe makes both. I don't know. But everybody involved, well, they were clinical trial, but it was, you know, four authors worked for the actual company four or five authors. In the abstract, they didn't even talk about histologic clearance in the abstract. Is that insane? Since when do we treat cancer and say, well, clinically, look like it was gone? Like histologic clearance is the gold. Is the gold standard? I mean, do you look for histologic clearance after you do an EDNC? I don't know. If you want to look at it in the effectiveness of a new drug or what I'm not maybe not a new drug, but if you want to look at the effectiveness of a drug in the treatment of skin cancer, you don't put out a study that says clinically, they look like it was gone. Like clinically, it looked like she didn't have a syphilis. Yeah. Like get out of here. Just to know Pat and is not talking about Ferris, all right. Thank you. I appreciate that. Okay. And I don't. So how I feel about these pharma funded studies, I think this, this just really. There is no way to do these kinds of studies unless they are funded by the company that is going to make fun of it. That's fine, but they should be very, very honest that look, this wasn't that good. And it's actually more inconvenient for the patient. You call up a patient with a superficial basal carcinoma. Hey, go to the, go to the pharmacy, pick up your affidavits, use it twice a day for four weeks. You don't have to come back here. You don't have to decrease it. We don't have to sit there and like scrape it because they did like debris each lesion. And then we're going to put this on and then you have to hang out for three and a half to four hours. And then you come back and the light's going to hurt. But they also have like, you know, field, like, you know, field cancerization, right? So the way that I would see this is in the person who has a bunch of, you know, AKs, a bunch of, you know, I want to do a field therapy. This is an option. And there are patients who like PDT. I mean, I see them and they're like, yeah, I like that PDT. I do not like that affidavits. Creamy. You get me. So if I could say, like, kill two birds, sorry, feed two birds with one stone. That's how we say things in academia now because we don't kill birds, but we only fooled them. So, you know, we're harmed in the making of this. What did you say, Ferris? If you could feed two birds with one seed, no one's gone. A scone. A scone. Oh, like a muffin. Okay. So, you know, you get field treatment, you get treatment of your, of your BCCs. I, I think it's not a, it's a good number to have to know. And I, I guess what I don't love is a lot of times when you have like clinical clearance or an open or maybe histologic clearances done in most studies. But like a lot of times these like cancer therapy, you know, basal cell treatments, it's like a single right. It is, there's an, it's not randomized to anything. It's a single arm study. And as we know, based on actually studies, we did at Pittsburgh biopsy gets rid of a lot of basal cells. And I think like most, most surgeons would say that for low-risk skin cancers, a lot of times you go in and there is no visible tumor. So, you know, they actually did it the right way. Right. And they did take a bunch of stuff that had already been biopsyed off. No, and I think the biopsy, specifically they said like a little three millimeter punch. Like I don't expect that to actually clear a, right, asal cell. I shaved and yes or, but they did it in a specific way. So yes, fine design. But the numbers aren't good. I, I guess I'm just not a huge PDD fan. And I was going through NCC and guidelines. You know, so the NCC and guidelines for field cancerization, they actually say five FU is the preferred treatment and they actually like adding the calcipatrine to it. Now for superficial basal cell carcinoma, they actually say a mcguamod is the preferred therapy for superficial basal. And that's, that's probably my least favorite treatment. It is my least favorite treatment too. So, you know, if this were squamensite too, I would be like, I know that that's not going to be my, you know, PDT's not my choice. Superficial basal cells don't do that well with, you know, I, I think with either a mcguamod or five FU. Oh my god. It works great for five FU. And there's data to back that. Yeah, I feel like I feel like squamensin site to do better with the combination. And there was a head head study of five FU, mal PDT, a mcguamod and a mcguamod was superior to mal PDT. I think that's why I've got the NCC on guidelines like Goldstar recommendation and topical five FU was non inferior to mal PDT. It reminds me by the way, what's the brand name of the mal drug? Is that amelose? Amelose. Amelose, is this the bio, is it biofrontera or who's do you know who the company is? Biofrontera. Yeah. Okay. And that's, is that different from the people who do the carousel fixers at the same company? That's, that used to be do so, but I don't know. They, they've all changed ownerships. I'm so untainted in this unlike you, Matt, I don't even know who makes it. Yeah, I don't know. So, but amelose. Okay. That's, that's useful. Don't quote me on that. Okay. All right. So, let's, I would like to sponsor this episode in which case. So Patten, I would take your thing to be that you personally do not like PDT as a therapy. However, you would agree that this had an 80%-ish cure rate and what abs would be a reasonable -- 66, 64, whatever, percent cure rate. That was crap. You have to be histologically clear. If you were not histologically clear in 30 some percent of the cases, that is not 80% out of your -- No, it was not. It was 76% for the gel versus 19% for the -- That wasn't the number that I saw in the text, love. Six, six, seven. Here it is. The percentages of participants with complete clinical and histologic clearance were lower. 64.1% of participants in the 10 ALA group showed complete clinical and histologic clearance compared to 4.8%. That is 64.1%. Yes, but -- That is not 76%. No, but if -- just if you look at histologic clearance alone, so you had to guess, is this clinically clear? You could have things that were histologically clear even though the investigator wasn't sure it was -- it could be -- oh, I think it is still there. Then you take it out and histologically it is not. So that would be histologically clear but not clinically clear. Pat, but your main thing is you thought they oversold it in the abstract and article and they should have not have talked about it so positively. The editors should say, you can't put clinical and have that be the number in the abstract. We are talking about cancer. histologic clearance put that in there. It all depends how they wrote the protocol and what was your primary endpoint? Just saying. All right. Pat, let's -- Now we know what the data are. So basically, we know that this works. So if you -- it's a reasonable thing for a patient who was to be like, I don't want to put a cream on for a month and have like an open oozing sore for a month. And I don't want to get a surgery and have a big -- I want to minimize my scar while minimizing my downtime. That would be kind of the ideal patient for this. And I need field therapy anyway for all my AKs. So what the heck, let's try this. Things do and they're actually better than PDT2. Again, had to had New England Journal's medicine study. Yeah. I agree if you said what the better treatment for AKs, it's 5FU. With longer downtime. Right? I said this would be for somebody like I really don't want to have hamburger face for a month or two months or 21 days or whatever. Okay. Fine. Alright, Pat, let's go. What do you got? August 2025 issue, British Journal of Dermatology. Janice, kind of signal transducer and activator of the transcriptions signaling pathways involved in the immune mechanism of bull's pempagoid by Chung et al. So if you've been paying attention, you know, Dupy is now FDA approved for the treatment of BP. But if you were really paying attention, you would know that the numbers from the adept trial weren't spectacular. I think Dupy can be a great drug for some of our BP patients still in need for non-quitter crystalline therapy for the patients that don't have that great response. Jack inhibitors appear to be somewhat effective for every other disease in Derm. So wouldn't they work in BP as well? So first part of the paper, very basic sciencey, kind of quickly go through first experiment. What genes are differentially expressed in BP patients compared to controls? Jack III and staff III are in there. Interestingly, Jack I had a lower expression in BP patients compared to controls. I thought that was weird. Any know, histochemistry verified Jack III, staff III protein expression of BP patients compared to healthy controls, fluysis, etometry performed on both peripheral blood cells of BP patients and controls. Markers that were measured weren't really different. Blister fluid from BP patients showed high levels of these, I don't even know, CD 163, positive monocytes macrophages. I wasn't really clear with the significance of that population was. They looked at chemokine and cytokine levels in BP patients. Plasma blister fluid compared to plasma of controls and blister fluid of Stephen Johnson and T.E.N. and burn patients. You can see the differences in figure three. I'm not going to go into great detail. They did some even vitro testing with some of the Jack inhibitors, Tofa berry, Upa, Ritla, determined that Tofa and Ritla had better inhibitory effects compared to Upa. But Barry seemed to do pretty well too. So I don't know. Anyway, they retrospectively evaluated the efficacy of Tofa in A patients with refractory BP. Significant reductions in BP dye and NRS scores, numerical rating, itch scores. And all A patients, they seem to reach, see a complete remission within a few months of starting the Tofa. If you look at the BP dye and the NRS scores, significant improvements after starting the Tofa. They followed cytokine levels before and after a grand sign BCCL-17, CCL-18 improved, and BP-180 titers decreased. So I don't think this is a huge surprise that the Jack inhibitors could be something to think about with our BP patients. What do you guys think? I mean, it could be. It could be patent. Looking at the table. All the patients were put on 8 milligrams of methyl prednis alone, but that's kind of a low dose. I mean, it's like the numbers, right? The problem though with, if you look at the Dupy numbers from studies that were done like this, it's like 76% of patients with Dupy reach complete remission. And then when it was really rigorously studied and randomized controlled, it's nowhere near 76%. 8 out of 8, complete remission. 8 out of 8 complete remission. Right? I mean, that's in a month after starting the drug, the itch scores went from, you know, 7s, 8s and 9s to 1s and 2s. Yeah. It was. And you wouldn't see that with that steroid dose alone, right? Would you say that is not what you, the response you get in 100% of people? I mean, it's really. 8 milligrams of methyl prednis. That would be 8 milligrams, right? So like 8 milligrams. So methyl prednis alone is it five to four, right? That's how I think of it. So I think it's 10 milligrams of pred. Yeah. Isn't that? That, I don't know. Let's, let's, let's, I'll look it up here. Let me, well, let's, we, we, we, one of you look it up while I start with whenever I go over to do a mind. But I mean, this, to me, this was like, now I agree with you as well, not unexpected, right? But where, where this is going to be like super useful is when topha goes generic. Like right now, it doesn't, you never, ever going to get it, you know, topha approved. So really, you're limited to upa and, and the other drugs that we have. But it sounds like they thought topha would be better mechanistically. So, you know, since it's mostly a jack three inhibitor and upa and abro or mostly jack one, two inhibitors. So maybe this is the disease where so far it hasn't seem to make a difference like a jack is a jack clinically. But maybe this is the situation where it is. But topha should hopefully be generic before too long. And this will give us a great, you know, if the other stuff we've got doesn't work. I don't know. Do you think that five of topha is safety wise? Do you think that's going to compare to retuximab? I don't know. I have used topha before when, you know, like I had a patient with alopecia ariata and before the other ones came out, we did get topha approved for them. I mean, I wasn't too. He was young. He was healthy. Yeah. BP patients are not that. But, I mean, retuximab is very immunosuppressive, right? No. Okay. So. I've not seen horrible infections in those. Okay. You actually do okay. That's all right. That's all right. I think there was a good issue in COVID. All right. But so Pat, if you personally or your relative had to take either topha or retuximab, which one would you give them? Is it depend which relative? That does. Yeah. No. I think it would depend on severity disease. So I would say with kind of mild disease where they're not getting away from us, like, you know, we should bring dupy back into the picture. That's where dupy I think is. Yeah. I'm talking somebody who needs it. Somebody who needs it. So let's say they fail dupy. If they are blowing up and their titers are really high, I'm going to convince them to go get retuximab. But just because like you blast them with their tuximab, B cells go away, titers go down. They come off prednisone. It's really, really nice. If they were in between that mild and blowing up, I think and I could get them topha. I think I would talk them into that unless they had, I guess, I don't know, thromboembolic stuff. I don't know. I don't know. So you're basically sounds like you're saying from a safety perspective, you'd probably prefer topha over the retuximab. A little bit. I don't know. I'm pretty safe in my hands. I would certainly say, okay, patient doesn't want to go get IV. Topha over methotrexate cell septin, your ancyclofosamide. Like, yes. Maybe both. Have you used it in any BP patients yet? No. The only thing I've used is do crabocetin. but because I had patients with psoriasis and BP and I could get that FDA approved. Oh cool. Okay. Good results. Have you used much reflumolation and BP? No. It doesn't work for everything, Matt. It's, yeah, I bet it works for BP. Is there any evidence, Pat, on that other off the top of your head, do you know, is there any evidence for a premolation BP? Off the top of my head, I'm not aware. Okay. All right. All right. Well, that's a good, it's a good segue into my other, my next three articles. Number one, I'm going to start with here is a premolation. And anytime I say a premolation, you should hear that I am saying to use reflumolation. This was a 12-week open label, but randomized trial for Vidaligo. So they did a premolation. So standard therapy plus a premolation versus standard therapy. Without a premolation. And so it was open label. So hard to know like whatever. Now their standard therapies were tailored to the patient. So they had some people who got narrow bands, some people who got topical steroids, some people who got aero steroids, somebody got a lot of topical tackle line mispo. That was all pretty evenly balanced. Biggest takeaway, the premolation worked. So premolation was better. So about 90% of people, their disease was halted compared to 70% of standard therapy alone. But more importantly, repigmentation. About 90% of people 14 out of 16 had repigmentation going on compared to 2/3 of people getting standard therapy. So basically the takeaway here is that tells me the PD-4 inhibition. I don't know how well it works for Vidaligo. But this gives me some evidence that it does something. And so it now gives me yet another disease where I've got an easy, completely safe, extremely cheap drug that I can use as my first line agent. Listeners, regular listeners, you know that there was also recent evidence that plaque winel 200 milligrams once a day. So very low dose. S-Mephiccy in Vidaligo. So now we've got two non-eminosuppressive drugs that we could use as combination therapy. If we wanted to, in Vidaligo, staying very cheap and very safe. Confirming. Nobody got a topical jack in that study, right? Ooh, interesting. Let me see here. So the study was out of India. Let me see here. So here's what people got. So a couple of people got narrow band. Four or eight people got systemic steroids. Most of them got topical steroids. Most of them got topical tachyrilitis. One person got his a thiaprin. No, nobody got a topical jack. All right. So PDE4 inhibitors. Now we're going to stay there and go to another PDE4 inhibitor. Another PDE4 inhibitor article. So this time we're going to go to psoriasis, which is against regular listeners. We'll know I stay away from psoriasis. This was a study that was funded by the makers of a premalast. Title of it. Oh, and I didn't give the title of my last articles. Sorry, I asked if anybody wants to look it up. It was a premalast ad on benefits over conventional drugs in unstable non-segmental vitiligo a 12 week single center randomized controlled trial. This study is benefits of earlier a premalast initiation in patients with psoriasis and limited skin involvement results from a real world retrospective study. Here was to take away. People with a little bit of psoriasis. So mean BSA in this study was roughly 5%. The people who got a topical and never went on from a topical did not do as well as people who got a premalast and early a premalast initiators got dramatically better a lot faster than a lot earlier than later premalast initiators. And so then whenever you look at the data, if you had a little more BSA, you were more likely to get early a premalast. If you had less than 5%, you were less likely to get a premalast. Early the main takeaway was even for people with mild psoriasis, it makes a lot of sense to put them on a PDE4 inhibitor, even if they've got just a few percent BSA, you're much more likely to get them to clear or almost clear if you initiate a premalast early, which again in my mind means initiate reflumalast early. Even if people with mild psoriasis. Okay, I will also say it's harder to have a significant PASI response in people with more mild disease. So if you're like, oh, the people who, you know, and maybe they got it later, right? So if you got somebody with a PASI of 4 and somebody with a PASI of 8, it's easier to get a PASI 75 response in the PASI of 8 than in the PASI of 4. And the PASI of 8 is more likely to get drug early than the PASI of 4. Yes. And they actually did a good job here. They, and I should have said this, they used BSA as their main outcome measure in order to kind of account for that. So it was getting people down to, you know, less than 1% BSA or 75% improvement in BSA. And it just happened much sooner if you started a premalast sooner. So. And then patent anything you want to add there? Not another plug for a reflumalast. No, we love reflumalast. Yes, we do. We do. We do. For the LIGO psoriasis. Everything now. Yeah. Everything. And the my last one as another psoriasis AD1, this was just the first good article I've seen about. So this was characteristics and management of follicular events and contact dermatitis and patients using the PINROF cream for the treatment of a topic dermatitis. So this was kind of a deep dive into the follicular events in their clinical trials. Main takeaway, most common on the legs, it had an earlier onset in a topic dermatitis than it did in psoriasis. So in AD, the typical onset was about two to three weeks in psoriasis. It was at about a month. So then the things that seem to make it more likely are perspiration, occlusion or overuse. So using it like twice daily. And then there's no specific therapy recommendation. Basically, it was stopped the drug to the affected areas. If it goes away, which it will typically within a week or two, you can start the drug back up. If you want, you can try some topical steroids. You could try a chratalytic, especially in psoriasis. You could try, you know, OTC adapolline. But basically, it is temporarily discontinued. The PINROF, IE Vitama, assuming that it goes back, that it goes away, then you can restart one. Sit goes away. That's pretty much it. Now, if the disease went away, obviously, you don't need the discontinued or to restart it. But assuming the disease is still there, once the flick of their events are gone, you restart it. So nothing new here, really other than most coming on the legs. And it happened earlier in AD than it did in psoriasis. Those were kind of the two takeaways. Pat and I'm guessing you hate, I think I'm guessing you don't like Vitama. Or do you love Vitama? I think Vitama is great. Okay, Pat and the loves Vitama. Ferris, what do you know you like Vitama? Anything, any pearls from either of you with Vitama for either psoriasis or AD? No, I just, I think you just have to tell people here are the side effects that can occur. And like, if you get the folliculitis, don't be freaked out by it because patients do not like it when they get it. I don't know. I had some of the earliest cases in the trials. I tried like topical clendomycinemotion, didn't really. Yeah. Maybe it wasn't the most effective thing, but you know, we didn't. Maybe I would try a little topical steroid and just say, wait it out now. Yeah. And the, for anybody who's not familiar with it, it does, it looks more like carotosis pylaris than it does it rate like inflammatory KP than it does regular old folliculitis. The pearl that I usually use is that especially for people who've had psoriasis for a while and used topical steroids before, I will always give, tell them to use Clubatus O1sade and Fatama once a day for the first couple of weeks because otherwise I've had people come back and be like, I use this for like two weeks. I didn't see much. Clubatus O works much faster. So I just stopped it and use my Clubatus O instead. So it, I usually will do the two together for the first two weeks and then tell them once you're, you know, once it's a lot better, stop the Clubatus O use just the Fatama because we're trying to get the remit of effect where then you won't have to use anything for a long time. That's, that's my psoriasis Fatama pearl. All right. That I think does it for this week's episode and he last comments from either of you. Now it's hard to compete with six papers. Oh, oh, Ferris just because I said that you usually do things that are to erudite, erudite. What's, I don't even see that. That's how you know it. That's how you know if you're erudite or not. That's right, if you can pronounce it. If you can pronounce it. [LAUGHTER] All right, so thank you. I would say thank you all of our listeners for tuning in. I hope you learned a few things. I hope you laughed once or twice. And mostly I'm hoping you're planning to join us next week. Till then, I'm Matt Zyrus. I'm Tim Patton. And I'm Laura Ferris, and we are Derms on Drugs. [MUSIC PLAYING]