♪ ♪ Hi, I'm Dr. Matthew Zyerson. Welcome to Derms on Drugs. A video podcast brought to you by Scholars and Medicine. Derms on Drugs is where cutting-edge Derm meets the medical committee. I'm Matt Zyerson, each week. I'm joined by my residency buddies, Dr. Laura Ferris and Dr. Tim Patton. And we're going to use our 60 years of combined Derm experience to discuss, debate, and dissect the hottest topics in Dermatology. It's everything you need to know to be on the cutting-edge of Derm and it'll be the most fun you've ever had while learning something useful about the skin. So tune in every Friday when we drop a new episode only at Scholars and Medicine and Spotify at this point. And so we're going to go ahead and jump right into it. I know Dr. Ferris had a big night last night at the Duke UNC game. Now that she's chairwoman of Dermatology, I think she took some poor student seat. Told them it was not allowed in anymore. So, but, you know, let's go ahead and see what she's got to tell us about today. Dr. Ferris, once you go ahead. All right, hopefully I'll fare better than the tar heels did last night. But so the first paper that I'm going to talk about, it was just published in Nature Cancer, efficacy and tolerability of neo-adjuvant therapy with we're just going to call it Tiva because I can't pronounce the formal name. A cutaneous basal cell carcinoma is a phase two. It's the neo-BCC trial. And so this is a small study. It was 18 patients with, you know, what we would call difficult or what they call difficult to resect basal cell carcinoma. So that, you know, how do you determine, you know, which patients are difficult to, you know, to resect or what do you call is like locally advanced as always sort of this ongoing trial with basal cell. But 18 patients, open label study, they got six cycles of T-Vec. And then they had this sort of interesting primary endpoint, which is, was the tumor then resectable without the need for plastic surgery, reconstru, to do the reconstruction. So basically, didn't need a flap, did it need a graph. And so this actually was terminated early because it met that endpoint. And so what they found was that 50% of patients did not need a flap or a graft. They also were able to, there's a lot of basic signs in here. I'm going to kind of focus on the clinical aspect of this. But, you know, big thing in treatment of locally advanced tumors or neo-adjuvant therapy, particularly is what percentage of patients reach a pathologic complete response. It was a third of patients here. - Oh, wait, wait. - Here's hold on a second. So do you inject this stuff into the tumor? - Yes. - Or do you, okay. So it is, it's, so there-- - Intraternal delivery. - All right, so that's why-- - Well, T-Vec, just to remind people, HSB engineered to express GMCSF. Okay, so it's a herpes virus. - And you inject, so that's why they're studying it for basal cell because as I was looking at this, it's like, why the hell aren't they using this for, you know, pancreatic cancers and liver cancer and brain cancer? Because it's easy to inject it into the tumor. - You have to have accessible tumors. - So this is FDA approved for melanoma specifically. - All right, okay. - So, you know, so this is looking at it for basal cell, why basal cell, basal cell tends to be sort of a cold tumor microenvironment, they can be hard to treat. And so, you know, key, just to go not too deep into the science, but if you look at the patients who had good pathologic responses, they had increased levels of CD8 positive T cells, CD20 positive B cells, CD68 myeloid cells, and a decrease in CD4 positive T cells and particularly T-Rikes. They, the tumors that did not do well were infiltrative basal cells. And then the other thing that they said was, you know, they looked and said, what percentage of people had, you know, subsequent basal cells, it was two, which was lower than they would have expected. So, you know, their argument was, you know, potentially this is going to prevent future basal cells. Everybody kind of did better. All the tumors got smaller. Small study, hard to know what to do with it, but, you know, interesting and potentially this is a way to sort of change the microenvironment and basal cell carcinomas, maybe make them more likely to regress, regress, maybe even make them more likely to respond to other therapies too. - Do they get, this is going to sound stupid, and I say a lot of things like that. Like do they get, like do they get cold sores? - So interestingly, one patient had to, had an early termination because he had basically like pyraxia. So he was the one, and he did not have pre-existing IgG and IgM to HSV. So it was like getting a primary HSV. If this gets out of control, you can actually treat them with like a cyclovir as well. - So do people who have a history of herpes do better or worse, or did they not really talk about that? - They did not really talk about it. There may be data from the melanoma world, but I don't know. But you know, interesting, interleasional, on-calytic viral therapy, probably sort of where we're going to, I think, start moving with particularly non-melonomous skin cancers. - It's super cool if we ended up doing it for warts, like one virus and another virus, and see if it worked, hmm? All right, Pat, what do you do? - There are expensive warts there. - There are expensive warts therapy agree? - Yeah, okay. There are these, you know, difficult to resect basals. And so it's going to be interesting to see what wins out in the neo-adjuvant care, right? There's, they're studying intratumeral immune checkpoint inhibitor therapy. You know, the systemic therapy to shrink these guys before surgery is, it's just kind of toxic. It's hard to tolerate. So I think intratumeral treatment makes a lot more sense. Less toxicity. Right now it's going to be, is it going to be the T-VAC, or is it going to be the injector in the hip? - It's a metlamap, or will it be both? Maybe it'll be one on the other. - It would make sense to use them together. - Yeah. - All right, Pat, what do you got? - All right, I did the buried, a writless switch in alopecia riyada. So, - Oh wait, wait, wait. Before you start, I want to say last week, Pat and said, "Doesn't make sense to switch from one jack inhibitor to another." I remember that. I think, yeah. I don't know, is that what I said? - I thought he said that Ferris DeSend. - I said just stay on the jack. We were talking about, - All right. - Okay. - Basically stop if you walk into the response. - Okay, all right, all right. Pat, where'd you go? - I disappeared. There I am. - There you are. - Well, I mean, I'm the beauty of the show. You lose me. - Yeah. All right, 2020. December 2024, clinical and experimental dermatology. Efforty and safety of switching from bare-sitting to writless sitting have been severe alopecia riyada by Chen at Al. It was a retrospective case series, 15 patients. So these patients, three things. They had severe alopecia riyada had been, you know, so salt score of 50 or higher, had been on berry for at least six months, didn't want to continue or increase the dose, and had stopped berry for at least three months. So these weren't really switchers. These were, I stopped the medication and hate. You want to try this other one three months after you stopped it. Switching kind of implies like right away. - Yeah. - Not that that make a difference, but I think the point being berries washed out of your system. So this isn't a berry effect. This is writla, which may or may not be true. But anyways, they were placed on writla 50 milligrams daily, followed for 24 weeks. 60% of those 15 patients responded 40% did not. So, you know, something you can tell your patients, even if you haven't had a great response. And this one study, more people than not responded. - I mean, that's actually a little better than their phase three results of just treatment naive people. - Yeah, I think they were prime. I think the bear sitting up did prime these people a little bit. - Yeah, yeah. - So anyways, two graphs, median, salt score, median, DLQI, both improved with patients that started writla. Univariate analysis, if you had no response to the bear, you were much less likely to response to writla. And in no other factor like age, sex, comorbidities, duration of current AA, A-A-A-Tike was found to correspond to achieving a response. They have a table that really allows you to go through each patient's five patients had no response to berry, like 0% improvement in salt score while taking the berry. Four out of five of those patients had a zero improvement in salt while taking writla. So if a patient has absolutely no response to berry, it's not like there's a chance it really isn't going to work, but it's not looking good. The responder really responded, went from a salt of 100 to a salt of 11. A couple things about her, she was 12 years old, which was a lot younger than the other non-responders. And she was also on two milligrams, whereas the other non-responders were all on four. So I do think berry primed them a little bit. I know they stopped at three months, but you know, there was a discontinuation trial with berry in it.
three months, only 20% of patients lost their benefit. So I still think Barry was still having a biological effect. So I think Barry people may say, well, it's not really fair. If these people stayed on Barry, we probably would have seen the same responses and the same non responses. But you can switch. I did it with one patient. He was at six months. It was kind of like the study. And he wasn't really getting a great response. And you know, you know, Ritlis said, maybe knew it was available. And so we did switch him. I haven't seen him back yet. It's kind of cute story. He has alopecia universe Alice. And he doesn't care. He's married and has a kid, but his kid has AA. And so he was like testing himself out to see, you know, it was just a medication that he would like put his kid on. It's kind of hot. It's like a little, a little hallmarked movie. Now I'm going to, I'm going to announce it officially right now. People have now learned everything they need to know about Jack inhibitors for alopecia. He out of from terms on drugs. You don't need to listen to Brett King or any of those other supposed experts anymore. Ferris told us last week, you give him six months on a Jack. And it was riddle was the study. And if they haven't gotten better, they're not going to get better. And so now we know after the six months, if they've had no regrowth, yeah, it's not even re probably not even worth. So that's one. If you get six months of the Lumian at four milligrams, another happens is probably not even we're trying riddle. I mean, you still can. But you give him six months. They haven't gotten better. You switch. And there's a 60% chance they'll get better whenever you switch them. That's it. If they had some response. All you need to do right. So yeah, having a little like, like there's right with a little bit of a response. Right. If they get a little bit of a response, it's still reasonable to switch. But if they get absolutely no response at six months, probably not even worth trying the other one. Well, would you, what would you do in that? I think we talked about it last week. I hitting them with pred at that point, maybe make sense and keep them on the jack totally make sense. Hit them with the side would do like probably 20 for a month, 10 for a month, five for a month, you could do 40, 2010. That was the study. The right, the eight patient case series was doing that. And then all of those patients re grew and then maintain their regrowth. But I think you really are immunosuppress. I mean, hell, I wouldn't want to be on a jack plus prednisone. On his own. Yeah. You know, yeah. Okay. All right. Fair she got anything else? Nope. All right. Let's go. It's going to my study. So this was the treat. No, it wasn't treated with something else. I can't remember the name of the study. Check the next study. Chronic hand XMA in adults cross sectional survey, 60,000 people in Canada, France, Germany, Italy, Spain, and the UK. This basically confirmed. So this was a big study that basically confirmed everything we already knew. So now we can be pretty damn certain that the prevalence of hand XMA physician diagnosed hand XMA was a little lower than expected. So it was about 5%. Now if you use the Zitton non physician diagnosed, just hey, my good hand XMA, my hands get an itchy rash. The number goes up. But basically things that I thought were interesting. 20% of people had dermatitis at some point in their lives. 9% had hand XMA at some point in their lives. 6% reported hand XMA in the last 12 months, 4.7% physician diagnosed hand XMA in the last 12 months. Biggest things were as we already know, male versus female females have more than males. It was interesting. There was a big difference in in countries. So like in Germany, it was very low at 3.5% in the UK. It was high at 6.4%. People with jobs had more hand XMA. Interestingly, people in urban areas had more than rural areas, but the survey was like 80% urban 20% rural. So hard to know what to make of that. And then the highest prevalence was in people 30 to 39. And we can really see that in the forest plot, right? So it's a really 18 to 29. Then it goes up for 30 to 39 and then drops by decade up to the age of 60 to 69. Don't know that might be that like old people don't wash their hands or it might be the old people skin gets tougher, but kind of hard to understand because you would think of less barrier function in old people. They're not going to work. So they're not getting work exposure. Yeah, that makes way more sense than anything I said Ferris. So good. That's why it goes. So good work. So really nothing terribly new here. This is what we already thought, but it's a 60,000 person study. So really confirms and give this good stuff on it. Biggest pearl I have for hand XMA was during COVID. We actually got a number of good studies of like what mattered? What kind of soapy use doesn't matter much? How much moisturized doesn't matter much? So moisturizers don't help a whole lot. What does help is washing your hands in cold water and it goes back to we tell our patients don't shout, you know, if you don't take long super hot showers because it melts your inner cellular inner intercellular lipid, let's get rents away. Same thing in hand XMA probably that the hotter the water, the more you can remove the intercellular lipid. That's the one pearl that I've got for people right now. You guys have anything anything else you want to chime in about this one before we bring our guests on? Do we think weather like Canada, UK had higher rates? Do you think weather matters in chronic XMA? That's actually a great question. So I think that changes in weather matter a lot. So going from hot to cold and cold to hot, right? Our skin isn't terribly well-divined for that. And I do actually think cold weather matters, but again because of the changes, right? So your our evolutionarily, our skin is never in the until the last 50 years. Our skin never experience going from 10 degrees to well kind of did, but from 10 degrees to 80 degrees, you know, 10 times a day as you went inside and outside. So when it's hot, when it's 90 and you come inside and it's 70, that's not nearly as big a switch as going from 10 degrees to 90 degrees or from, you know, from 10 to 70. So I do think temperature matters, but I'll be interested to hear what our guest thinks about this. Patent, what do you got? Anything? No, I wasn't quite sure what the point of this was. Like you said, it was kind of stuff that, okay, maybe you've never been studied on this big a patient, but is anything shocking here? I mean, Leo was one of the authors. So I think they're doing like a little pre-market-eant-type. They're really good. They're strong and they're sponsored and they're ready. They got a jack and hybrid coming for handexana. And so let's let's go ahead and bring our guest on. So we've got Dr. Yakub Thyssen, who is a professor of dermatology at the University of Copenhagen in Denmark. He was the lead author on the European Handexana Guidelines that came out several years ago. Now conflict of interest. Dr. Thyssen does work now doing R&D at Leo, but he is looking for new molecules, not really doing work on their existing molecules. So we're not really going to talk about Trailichinemab, i.e. adbree, or Delgocetna, which is the new handexana drug that is coming because those really aren't the errors that he's working on. But so Dr. Thyssen, great to have you on. Pleasure to be here. What a wonderful way to spend a Sunday afternoon in Denmark. So thanks for the invitation. You got it. So first, let's let's go right into kind of what Dr. Ferris has because I think it's a great question. So and I will again tell everyone, I think of Dr. Thyssen as the world expert on handexana, right? The European guidelines are comprehensive. The Danes have done the most work on handexana, sort of their classification system is what the whole world uses. So Dr. Thyssen, why don't you you know, what do you think is the role of weather and the seasonality of handexana? Let's kind of start there. It's such a good question. I'll tell you what, if you come to Denmark in the winter, you wear your sneakers out and you know, it goes from from plus like plus Celsius to minus Celsius, your skin will crack. Like your toes will crack, your fingers will crack, even though you have good mittens on. So the point is that cold is very, very important for skin barrier function and you have a bunch of animal studies showing this thing. But what's interesting is we have very big nationwide registry. So every day is basically recorded in the registries. If you pick up a topical corticosteroid or what happened in the in the pharmacy, you will be recorded. And we had a PITSD student from the US, Nathan, you just made all Americans nervous about Denmark. You will be recorded. But it's great for research. I will tell you, but we had we had Carson Hammond. So he's a dormitologist out of Phoenix, Arizona. He was here doing a PhD for a few years and he came up with the idea to study this. Like what's for 80 patients? Is there a higher consumption of topical medication and oral medication, systemic medication in the winner? And that was. And I'm fully with you. You know, that transition also is very important, what you just raised. And I know Peter Vise has done some very impressive studies showing when you take mice in and out of of humidity, it actually weakens the barrier and then you have more XM of prone skin. So I'm I'm right with you. - Okay. All right.
I usually monopolize our guests. So I'm gonna give Pat and Ferris to chance to ask some questions here before. I could sit here and pepper this in with questions for the next four hours. So I'll let the two of you jump in first. - Yeah, I guess my question would be how much of hand to Eczema do you think is, is really sort of either irritant or allergic contact related, right? So how much of this is, if we could actually change exposure or change what we're doing, how much of it do you think would get better and how much of it do you think is sort of more immunologic or genetic? - Yeah, so it's a great question. I'd say that irritant contact dermatitis, that's really the most important exposure that causes Eczema, whether you have atobic background or not. And then I think that at least in my country, if you go 30, 50, 70 years back, allergic contact dermatitis on the hands was something of great importance. But today when I saw my last patients about a year ago, I would rate it's about one out of 10 chronic hand to Eczema patient where allergic contact dermatitis could play a role, but that could also be in concert with irritant contact dermatitis, just remembering that many of these chemicals both at irritant and allergic potential. So what it brings me forward to is as a clinician, I mean, you have to take that interview and hear about irritant exposures and allergic exposures. You have to look at the hands, let's say you have a very localized lesion, just where the metal piece from a dog lesion something is exposed every day, and then you do the math. But I think that always keep in mind, it could be allergic contact dermatitis. Do advise your patient if you're suspect this to remove that could be fragrance allergens or a metal exposure, whatever. And if it doesn't solve or if you have easy access to patch testing, then absolutely, why not make the patch test? So that's the way I see it. But I mean, it's just my gut feeling, 10 to 15% of patient with have a relevance or have relevant allergic contact dermatitis, but not more to be honest. - Yeah, I can do you. So the thing that I have learned kind of helps my colleagues get this and helps patients get it. 'Cause I think that irritant contact dermatitis is a factor in essentially every single case of hand-exema. And the terminology, what I learned to say to people is imagine you got five showers a day. 'Cause the average American watches their hands six times a day. So imagine you got six showers a day, got in there, hot water, soaked up. Would you not expect that every single person would be walking around with dry itchy, flaky skin. And so some people are watching their hands 10, 15 times a day, but even if, unless you're, so I actually think a big part of the reason men have less hand-examined than women. And I say this frequently on the show, I think men are disgusting. And we just don't want to. And we wash our hands like twice a day, whereas women wash their hands like 10 times a day. And so that's why the average is six because it's disgusting men and clean women. But all right, Patent, what do you got? - I was wondering, 'cause you've also done some work about topical steroids and systemic effects of topical steroids. With bad hand-exema, I just, I never thought that that would be an issue. The skin on the hands is very thick, systemic absorption. Even if you're putting on steroids twice a day, for two weeks straight and can only take a few days off, I kind of tell those patients, don't worry about it. The back of your hands might get a little bit thin and you're gonna see, you know, tillangic tages and things like that in atrophy. Am I under counting just how dangerous topical steroids can be or am I ignoring the side effects in those patients with hand-exema? - I think your guess is just as good as mine. There's no reshort time aware of that will show that okay, you'll get systemic exposure after putting a club ed assault on your hands for a certain number of times. But what I will say is if you have other skin areas, let's say, genital where we know the absorption is just enormous. There, you know, two, three weeks of club ed assault for leach and sclerosis, there you can have cushion syndrome. So I mean, we know these are very potent drugs. And in 80, I really do think that it matters for systemic absorption and exposure. And I think we have pretty good evidence for this. That is very, very good register-based studies, indicating this, but we also about a year ago ran a study where it was an RCT taking tech climbers versus a momentum-zone furate and show that, you know, with systemic or with a full body exposure for two weeks, you do see corticosteroids go into circulation and it will suppress insulin sensitivity. It will affect bone homeostasis. So for me, I think, yes, that we know, I'll just try to go down to my point. But my point for hand-examine is just that, you know, and this may be controversial when I'm saying now, but I try always more or less completely, unless it's hypercuritotic, X-Mine-2-Avoid club ed assault. I think in hand-examine, it works, but it's just too much, because it will relieve some symptoms here and there, but there is a price to pay and it comes down the line, because you will destroy the barrier. And that's my point. So I think steroids on the hands, you know what, they work great, but if you take two potent steroids, there is a price to pay for patients. That's my experience. Patent, before I got like nine follow-ups to all the things you had come just said, but before I jump in, Pat, and when you got any follow-ups, you want to ask them. No, no, take it away. Oh, goddammit. So all right. Fisson. Sorry, sorry, by the way, I apologize for just taking the Lord's name and name. So fisson. I think Patent's Catholic, he has five kids, so he's got to be. So this is so, all right, number one, you just said something that nobody in the world of Durham gets, right? So I'm sure you've seen the liest his papers from like back in the 90s that three days of club A does all, and you stop making and releasing lamellar bodies. So you stop making intercellular lipid, right? So for people who like think in terms of bricks and mortar, you stop making the mortar and you can't do bear repair after three days of club A does all, which is why topical steroids have never worked as well for a topic germ as we would think. Because while we're helping with the symptoms, we are reducing bearier functions that we're making the fundamental problem of the disease. Worst, but my response to that has not been to not use club A does all. It has been, I have people use club A does all for two days at a time. So since a liar showed three days, I tell people, you can use it for two days a week. And then the rest of the time, I got them on something else. Historically, that's been a TCI, which I don't think does a whole lot, but that's been my-- so do you use any steroids in handexamine? Is there like you use beta-methasone, you use mometasone, or you just stay away from them completely? No, no, no. I would say TCI, I don't use for handexamine. This is atopic handexamine and not really anything palmar. So dorsal, TCI is fine. The rest that has been for me, topical steroids, really the workhorse in and out, Wigan, Wigout. But I'm just saying that except for the hypercuratoric one, my experience is that club etusol is just too much. So I swear to beta-methasone, I swear to mometasone. So I take it down a notch. And then one of my favorite studies is in Nils' Vayan from 1994, I think, in the British Journal of Dermatology, showing you use mometasone for chronic handexamine. And then you can taper to twice a week or three times a week. I know it works fine both of them, but you do see more side effects if you use three times a week compared to twice a week. So for me, my clinical experience makes with evidence from the literature is that a European group of three steroids, so moderately or a potent topical called steroids, that's the one I prefer. But I'm not against club etusol. But when I teach-- when I talk my residence back in the day, I would always say, be careful. It's a very powerful tool. Yeah. Sorry. Great. And it is. Yeah. And for those of us in America, a high potent topical steroid is a class two or three, which I agree with the Europeans, by the way, that it should be low, medium, high, and ultra high. But then the other thing Patten brought up, which I think is a great question, right? So you've done the work showing that there is a direct correlation between the probability of getting diabetes and the total amount of topical steroid used and the probability of getting us to a process and the total amount of topical steroid used. Do you have anything in your head that is like a-- I guess the bigger question. Do you ever bring it up? Do you ever say to a patient like, hey, or does that risk ever influence you? Never. Never, Brad. Never whatsoever. But I will say caring for 80 patients where you have significant body surface area, there, it comes into mind. So I can have patients that I will treat it with not kilo after kilo of topical steroid. But I mean, when you have significant usage, and they are very disciplined, and they Do listen to your advice about
you know, put it on as soon as you can and then taper and go to twice weekly application. So very at-fueled discipline patient with large body service area. I'm like, even though it works fine for you, it's time to move you to a systemic or a biologic because it's not good in the long run. But I never had the conversation around diabetes and osteoporosis. It's something in my own internal algorithm. It's too much, I think, for patients to digest. Okay, so there was last big question for-so I was the-I'm going to be the first author on the phase two study that insight did on-and we're allowed to use brand names on this show. So, I'm Celura for Handexima. And I got to tell you, it was freaking insane how good it was. So like-and these people were supposed to be nonatopic just Handexima, whatever. And I was like, I-like it was an order of magnitude better than Clubators all would be my guess. And I was like, oh my god, like as I think this is because you don't have the barrier impairment. But I think Jack inhibitors and conflict of interest, right? Jacob works for Leo who's got a- Jack inhibitor is going to be coming to market for Handexima. But right, based on what I saw with Obelura, I was like, oh my god, this is-like, do you think Jack inhibitors are going to completely change the world of Handexima? Let me try to give a political answer with my bias here. I think what we see is the topical steroids, they have worked well for decades. Derms know how to use them. There is a certain element of patient fear, and it works well for most patients. But there is also a need because of TCS, reducing inflammation, but come at the cost of the barrier. I think there's a need for these innovative topicals, Jack's being one of them. And among the new innovative topicals, I would say that the Jack seems to be the most potent, you know, fast onset of action, very strong each reduction. And therefore, I also see that these can be very useful for chronic Handexima, where it looks like they will have the indication, or at least we see in Europe, that there is one topical, Jack inhibitor that has the indication for chronic Handexima. So, I see this is a very good combination for patients because it reduces inflammation, but not at the cost of barrier impairment. And do you guys have to pin her off in Europe like the camera? No, not yet. I don't know whether the organ on has any plans to take it to Europe. But that's also a good product when you look at the data. Yeah, and what's fascinating about it is that it's the aerohydrocarbon pathway is the only pathway I've ever seen that actually stimulates barrier formation beyond just you remove inflammation and barrier gets better. So, I'm picturing in my head that the most effective topical regimen I could ever imagine would be to pin her off once a day and a Jack once a day to pin her off to stimulate barrier recovery, Jack inhibitor, to take away the inflammation. I have one last question for you before you go. So, you have been you were sort of a mentee early in your career of Torqueaux, a mentee, correct? Yes. So, he is the one who's done the best work on dietary nickel. Yeah. I think dietary nickel is the most underdiagnosed thing in the world of dermatology. I think that it is one to two percent of the population I think is walking around with inflammatory something from dietary nickel. What do you having worked with Torqueaux and I've never actually talked to him about this? Do you think about dietary nickel on a regular basis with hand examin other patients or is it something where you're kind of like it exists but man, I'm not too worried about it. The answer is I don't, but let me just you know flip back 40, 50 years because it's interesting. There were two professors at the time. You had Torqueaux menae and then you had this nose wine actually the same guy I just spoke about before on the Omeda son furia and taper into twice weekly three times weekly. So, they had two ambitious career ahead of them and Torqueaux menae he chose to go into regulating nickel exposure from jewelry, from buttons, from syphos, what have you and that led to the European regulation on nickel exposure, limiting exposure, limiting nickel allergy prevalence to a bare minimum. Now, Nilsfine did the opposite. He believed very much in what you're talking about that oral nickel exposure leads to a lot of eczema to problems and he wanted to understand and study that. And it was very important at the time. So, he showed in very convincing studies how much it matters and how sick patients were and how changed when they had a you know a nickel-free diet. But what just happened in Europe over the years with the success of Torqueaux menae's work on regulatory efforts is that it became less and less relevant with the dietary exposure because patients and we've documented this they went from having you know very often three plus nickel test test reactions to two plus to one plus to now doubtful. So, you know, the severity of nickel allergy and then might just decrease the decade by decade by decade and the more decreased, you know, the cutaneous response. The less nickel, the less the less the less diet mattered. So, I mean, it's just that's right. You know, that part of it I never thought about that we've got pretty good data that the longer you go not being exposed to an allergen sort of the less the more it takes to wake up your memory effect or T cell. So, your allergy gets less you know intense and so it had an occurred. I was thinking of the nickel-regulacences just bringing down the prevalence of nickel allergy. It never occurred to me that it also you but it's obvious whatever you say it that it would also bring down the severity of nickel allergy. So, I think the message for listeners here or viewers is that if you have a very nickel allergic patient with a three plus or two plus reaction, it may matter. But if you have one of those it's a doubtful or three pluses in a row, you like don't worry about it. All right. Okay. How about Matt? Can you drop in for listeners? Where do you send them for nickel-free diet information? Yes. So, there's a website called www.thelonicoidiet.com. There's also a textbook or not a textbook, a cookbook of the same name called the "Lonico Diet" that's on Amazon. It's like 30 bucks. I wrote a chapter in there called about nickel dietary nickel four doctors that is literally because most dermatologists and allergists don't know shit about this. And so, it's to literally cop for the patient to copy it, take it into their doctor and it's got all the references, everything else. So, it really is the only diet that we have. So, so yeah, compared in the US when I have any nickel regulations, so nickel was still 20% of people horribly allergic to it. It's the only diet of all this anti-inflammatory diet, baloney, and the the paleo this and the whole 30 and the that and the whatever. There's no real evidence behind any of that. Lonico diet is rock solid proof. We know which cytokines we know like it has systemic effects. The Italians talk about this systemic nickel allergy syndrome. This is the only truly anti-inflammatory diet. If you and you can get a test, right, you get a true test. If you're allergic to nickel, the diet might help you. If you're not allergic to nickel, it's not going to help you. But www.thelonicodiet.com and the textbook called the "Lonico Diet" on Amazon. And I have no conflict of interest, although I wrote a chapter in the book. I don't get I don't make a penny. A penny. A penny. Not one. All right, so unlike Pat who's very conflicted, don't listen really to much of if he recommends anything, forget it. Yeah, horribly, horribly in bed with forma. Just on the open payments. You can compare. 19 stands over six years for Pat. I think I owe them money. I'm probably going to get kicked out of the shows. I just won anecdote before I leave. That's a case report from Japan with an old woman or a middle-aged woman who went out to her well every day to carry in water. And it was so much nickel in this water. And she would wash her head in and get actually got allergic nickel-dermatitis on her face. And it was diagnosed. And when she stopped using the well water, she was fine. You were kicked because I get asked all the time by patients, do I need to worry about whenever I shower? And I'm like, no, it is impossible. There'll be enough nickel in your water to get out. This one anecdote, yeah. One case. Listen. All right. So, Jacob, thank you for coming on today. This was so much fun. And I want you to stick around if you don't mind for a few more minutes. So Patent typically does some trivia for us. And it's kind of the three of us against each other. You're going to, we got to wait for Pat and to finish answering the question. Reading the question. And then once you finish reading the question, you just shout out the answer so far for the season. It's Ferris 2. Actually, Ferris 3's Iris 1. So she's 1 twice. And we tied once. I have yet to win a round of trivia. Let's see where we go here. All right. I struggled this week. These are the worst questions. So I'm just setting this up. Because I didn't like hand dermatitis. And then I started getting into allergens and zyres would have cleaned up there. I can't have it. We got two that kind of
focus on Denmark. So definitely favoring Yacht. I don't mind favoring our guests. And then one that I'll sit you benefit if I know the answer. Oh, yeah, you're, you're, you're, you're, you're, you're, you're, you're fairies in me. Yeah. Okay. Let's go. And then one does have to do with patch testing, but it's pretty obscure and it may actually be wrong. Okay. And I have already lost to Jacob several times in ping pong. And I think of myself, that's true. I think of myself as a very good ping pong player. And he just wiped the floor with me. Wow. Okay. All right, first question. These are a bit worthy. I couldn't shrink them down. My, my research team took off this week. All right. Number one, according to world population review, 68% of the population of Denmark is blonde, which put them at number six, when ranking countries according to the percentage of blonde people of the five countries ranked above Denmark, which is the only one that is generally not considered to be a Nordic country. Germany. Germany is not Nordic and it wasn't Germany. Switzerland. You said, which one's not Nordic? Yeah, not Nordic. It's five. So there's, there's Finland, Iceland, not Iceland. They all have a bunch. I, they, those people consider Iceland Nordic. They, you guys own, I, I know, you don't that's Greenland, you guys own. Well, for now, let's see about that one. So we have five countries, Iceland, Norway, Denmark, Sweden, Finland, that's five. And then you want a six one with blonde. Yeah, there's one in there. There's one in the top five that is not. Okay. Could that be Holland? No, no, because Pakistan. No, really. Switzerland was not it. It's in the neighborhood. It's close to contact. I don't know what's close to. Yeah. No. All right. I'm calling it. It's only. Yeah. Okay. All right. Estonia 70% of the patient apparently blonde population. If I patients just so they get sick more, no, population. Well blonde hair. Yeah. Sure. Okay. All right. So that was, I mean, that's a little bit. Okay. Let's move on. All right. Ready? That's a good question. Bruno Block is considered to be a pivotal figure in the development of patch testing. Yodasin is like the father of patch testing. Bruno Block worked under him. And he was the one who like standardized it. He's like, here's our standard panel. Here's how you do it. Here's how long you apply it. Before then, it was like, no, that people would just stick people on stick things on your skin and see if it was a reaction. Okay. So he developed the standard series of nine allergens. Of these original nine allergens, which one is still included in the European and American standard patch test series. Samarisa. No. What would you say? Yaka? Nikol. No. Samarisa. No. Chromium. No. Formal in. Oh, what? Yeah. Is that it? Yeah. From Althehide. Son of a bitch. You've got two. Okay. One world renowned patch tester here. Amphus. I'll never be back on this, Joe. Whatever we want. We can say what? Yeah. So the other ones were Mercury, Turpentine, Naphthalene, Arnica, a leaf, Iota form and quinine and Formaldehyde. That was his original nine past. You know, I was close with Thymarisaal. But Thymarisaal is actually not on the American standard panel anymore. So that though you're right, that didn't count. All right. You got a third and final question. So far, it's pharis one. This is an Enzyra zero. Okay. Okay. So last week we talked about Niels, Ryberg, Finson and his Nobel award-winning discovery of treating cutaneous TB with UV therapy. Remember? Yeah. The Nobel Prize in 1903, I think. Dr. Finson was born a subject of the Danish kingdom, but he wasn't born in Denmark. Where was he born? Farrow Islands. I knew, I knew Faris and Zeyer said no chance of getting Farrow Islands. They make good salmon. You get good salmon from there. Oh, no, is that the Farrow Islands? Yeah. Huh? Okay. So this, this and one, Faris one, Zeyer zero. I remain far behind. You remain defeated. You're very consistent. All right. That was that was good stuff. Yeah, I could thank you for coming on today. This was pleasure. This was a great time. And yeah, I could just, you know, last week our guest was Dr. Weller from the UK, because yeah, I could have been I've talked pretty frequently about the Sun and effects on mortality stuff. So the that new study that just came out, he that was a yeah, it's you Europeans know what you're talking about. Always great. I love that topic. Toppy. Great. Thanks for having me. It's a pleasure. Thank you. Thank you. Thank you. Thank you. We are now going to break into our final segment of the week. So I hope you enjoyed our first two earlier this week. And so this is the six pack where we're going to go over six more articles that we thought were interesting and clinically relevant. And so let's get right into it. So Dr. Ferris, once you tell us about article number one. So this was an article in JAMA dermatology of Babet at all. And this is a mcwamod cream preceded by superficial curatage versus excision for nodular basal cell carcinoma. So this was basically a randomized study of 145 patients. Half of them got a mcwam got superficial curatage, which is basically like curating to the level of the adjacent skin followed by a mcwamod 5% a week after curatage five days per week. So five days on two days off for six weeks versus you know standard surgical excision. So this was the five year study. This is a five year follow up at the one year follow up. They actually did kind of see the same thing, which is that surgery is better recurrence rate is higher at a year. But this was looking at five years. And so if you look at you know what percentage of patients were recurrence free, it was 77.8 in the curatage and mcwamod arm 98% in the excision arm. You know take away for this is that excision does seem to work better. They did say that you know investigators thought that the scar looked better for patients who had a mcwamod, but there was really no difference in patient rating. So kind of a long process to go through this for patients and maybe in the end excision is just sort of better and one and done. Yeah, it's hard it's hard to see using this instead of curatage EDNC or curatage and cryo can't hard to see any reason to do this instead of those patent any thoughts. No, right. I don't see a lot of patients going for however many weeks of putting a cream on, yeah, yeah, I'm with you. All right. So curatage and mcwamod out. Derms on drugs not recommended. All right. Patent. What's next? Trailow kinemab for BP January 2025 British Journal of Dermatology by Magliat L. Offlabel use of Trailow kinemab and the treatment of bulls-penfaglite case series is a retrospective series of five patients at two different tertiary referral centers. They were, they had BP, they were deemed to be bad candidates for immunosuppression or had failed immunosuppression or had an adverse event from a prior BP therapy. They did atopic dermatitis dosing and four of the five patients were also started on 0.5 migs per day of prednisolone that was tapered but they didn't really go into the details of that tapering which I think is the most important thing in how you manage BP patients with other therapy, you know, with whatever steroid therapy, you're going to put them on. So what was it? The figure one showed the clinical photos before and after and the patients that had a complete remission. Two other patients achieved partial remission on doses of prednisolone of five and seven and a half. The text actually said five migs per day but that had to be a type we would you would kill people on that dose. And they did it at 12 weeks of treatment and then they followed them out longer. So yeah, longer term follow up. One patient died. He had a soft of geol cancels are going into the treatment. Three of the other four had either complete or partial remission still required prednisolone albeit the low doses two and a half or five milligrams. So of the like the one guy take the guy who died out, you had three of the four patients that still need to prednisolone therapy. That's comparable to the adept liberty, you know, liberty BP adept study where 80% of patients treated with dupy still required. I mean, that's a totally unfair comparison because that was a very well natural trial. So the take so the takeaway is probably similar. Probably similar to dupy. Yeah, interesting to see if these other aisle 13 will go after that that indication. Yeah, interesting. But you would expect that they would work similarly in the treatment of BP just like they do in atopic terms.
Well, but it tells us at least that I owe four blockade maize doesn't appear to be necessary For Pemphagoid which was an interesting question And two years we can talk about should you switch from one to another for me? That's right switching Switching these days all about switching. That's right. All right, so we'll go on to the next one which was mine. This was interaction between blood pressure medication use and Skin why not skin cancer actinic heratosis and Essentially they did a trinit so this was a association between the use of anti-hypertensives and the treatment of actinic heratosis of trinetics population-based study by Mendoza et al in the jade And this was interesting so we've kind of known for a while that it looks like hydrochlorothiazide in particular Increases the risk of skin cancer probably because it's somewhat photosensitizing So they looked at a bunch of different blood pressure medications in the need for treatment for actinic heratosis and basically what they found was that hydrochlorothiazide did Increase your likelihood of getting treated for actinic heratosis probably increased it by about 20% So interesting Right pretty we now should be thinking if you've got somebody who's got tons of AKs and BCCs and squames And they're on hydrochlorothiazide they should probably go onto something else interestingly Look like there might have been a little bit of risk with some of the other ones, but not nearly as big so Beta blockers from atopra wall had a little bit of a risk glossartin had a little bit of a risk associated with it looks like the blood pressure meds that have the least risk Peer-to-be-diltiasum and conidine But really by takeaway is that other than I had to just kind of stay away from hydrochlorothiazide If you've got somebody who's got a ton of UV-induced Premilligency malignancy you guys have any other Real takeaways from this one or other thoughts on it because we now have like four or five articles that have that have confirmed hydrochlorothiazide Increases this risk Yeah, I think um it this just sort of brought a case into it is what most of the data was on squamous cell carcinoma specifically I counsel patients to try to get on something else if they're on hydrochlorothiazide and they've had a couple of Particularly squamous cells. Yeah, I'm I'm terrible at this. I really do need to get into the habit. I don't think I You know you know suppression sure, but I I really don't But that's not all my radar and it needs to be I pledge here forth Yeah, it doesn't it doesn't cross my mind doesn't It's something I tell PCPs like when you give those like derm lectures like derm pearls for PCPs throw this in there It's an important one for them to know cool Okay, all right. Let's go on to our next article dr. Ferris where you got So this was um basically AI is better at talking to patients than we are so this was um over a thousand You know clinical questions 59 messages basically either The the doctor responded or they they tested to a my AI models and they use the stanford AI GPT model And if you looked at patient satisfaction it was higher with the AI It responses than the physician ones interestingly The physician ones were liked better by patients when they were longer But the AI ones it didn't really make a difference if they were longer So you know, maybe we ought to think about having AI rewrite our patient portal messages But there was a huge difference in how long right the AI ones were like A thousand fifteen hundred words the physician ones were like two hundred words right that didn't two hundred words Do you I'm like Yes, it was characters. Yeah, okay, okay, and don't forget these 250 versus 14 They're 1500 and these were real these were real doctors not dermatologists Uh The now did they look as well at the quality of the messages because if it was like The course of patients are going to like it better if they're like hey, do I need to avoid McDonald's in the AI? No, they they do you don't need to make sure that they were like appropriate clinical Information so that was it it wasn't that you know that that the they were giving the wrong information and just telling people what they hear It's not like oh here you can have an antibiotic for your cold. It's what wasn't that kind of level of So Ferris are you going to be implementing this in the UNC Department of Dermatology? Uh, I don't know if we're going to be doing this for patient responses. We are going to be doing AI scribing like a lot of academic centers. So interested to see how that Pants out okay, we're gonna have to follow up on that after when you when you guys planning to implement Uh, within the next couple months. Oh, that'll be interesting to see if it saves you because right it I don't think it to people don't think it's going to help patient care. They think it's going to save money Is that is that correct? It's the time save time There's something like uh, and over an hour of pajama time per clinic day like where you sit in your chart and it saves that and chart closure rate goes up So there's a lot of interesting data. Do you guys already have scribes? We have we have human scribes for some of our encounters. Right. So that's going to be the question is is it because it really it shouldn't be better than a scribe I mean, maybe it will be but it shouldn't be I'll see we'll see all right patent. What do you got? Uh, I just wanted to bring up two things that I had learned about within like the last six months I didn't want to go into details with the studies. It was uh, two anti-perspiration medications. Uh, so two medications two two two one device one medication to treat hyperhydrosis in the exylo one was soft peronium Something something known as soft draw Um, it's basically like topical glycopyrolated. It's an M3 receptor blocker Um Got approved last year and it just kind of went under my radar completely It's $1200 on goodRx. I don't see us using a lot of this Uh, the other meant the other device was this brella device. So brella I just went to the international hyperhydrosis society website and was kind of like you know, here's all our therapies and I saw brella on there I'm like, I've never heard of brella. Uh, so brella is this sodium patch that you slap on the skin The sweat mixes with the sodium causes heat And then you kill off the sweat glands and so you don't sweat anymore Um, just something you know to be aware of I actually talked to the brella guy It's definitely more of a cosmetic sort of way that that they want to do it you buy a bunch of these pads for like a hundred bucks And then you charge patients 350 for the treatment Um, I don't think either one of them or any better than Botox I don't know how well softer is compared to just topical like a perillate which you can get a compound deformities I don't see myself using a lot of these but just something like I had not heard of these and just nice to be aware of Do you guys use so the biggest thing I was surprised about with the sopironium like it had a lot of side effects like dry mouth 14% of people vision blurred 9% Uh, midrhyasis, which is your pupil doing something with 7% like 20 30% of people had an anticholinergic side effect Uh, do you do you use glycopyralate or oxybutynein Uh, orally for sweating Yeah, like a perillate. Yeah, I will that's the one I is Patten you oxybutynein or glycopyralate glycopyralate I've switched a couple of people to oxybutynein because they you know, like a perillate wasn't working Yeah, yeah Yeah, I I have more use oxybutynein and I think it works better but I just saw new data that like a perillate does not have a dementia risk on oxybutynein does So I may be switching back to oxybutynein Uh, so last one was mine and as somebody who does little to no surgery I still found this interesting so right the basic thing they looked at was tearing through right so whatever year So reason I do a whole lot of surgery and a lot of great surgeons So tearing through was a very common event whenever I was doing surgery on old people Uh, so right when you put your suture in and then it pulls through the skin and the main takeaway was As you already would have expected like the bigger the suture the less tear through there is But the type of needle you use actually played a big difference So they compared cutting needle versus reverse cutting needle versus tapered And tapered versus a cutting needle or reverse cutting needle tapered was kind of meaningfully better So the the way that I think about this if you put a stitch through and then you pulled hard enough To lift up a can of coke The cutting needle would pull through but the tapered would not Before the tapered would pull up you'd have to put a stitch through and then pull hard enough to lift up a 16 ounce like a bottle of drinking water. So it was how hard you would pull for a coke Versus to lift a 12 ounce versus how hard you would pull to lift a 16 ounce. So the Uh, I don't know if there's a cost difference between the different needles But it it looks to me like the tapered needles are probably what we ought to be using if we're worried about tear through What I understand is reverse cutting or probably better if you're worried about Maximizing cosmetic outcome at least as well. They said in the article But that that was just a neat little pearl Uh, and I thought might be useful any comments No, I tried to price it out. I mean I figured okay these tapes
it must be a lot more expensive, but it didn't seem that way. But pricing, gum sutures is kind of goofy to look up online. Yeah. Ferris, we know you put your people in a bubble for two weeks after surgery. Are you going to do? I didn't even know what needle I used. Like I was like, I don't even know what the hell we've got in clinic. Mostly use reverse cutting. Mostly reverse. Probably what you're using. Yeah, that's what I, okay. All right. You're going to change what needle you use, Ferris. I don't know. Maybe I'll try it sometime, but I guess it only matters on like the thin skin, right? So like a 25 year old on the back. I don't know if it's worry about this. Yeah. I don't, tearing is not common with the people that I operate on, because I probably take the really, really difficult, more likely to have a complication, and I send them to much better surgeons than I am. Yeah. I hear you. All right. Well, guys, I think that is our last of the day. Now I really want to encourage people to get on for next week's episode. We have such a fascinating discussion coming with our deep dive. So we've got a cosmetic chemist and Dr. John Barbieri from Harvard coming on to talk to us about benzene and benzoyl peroxide. You know, is it, do you need to worry? Is this a real thing? And if you do need to worry, how much do you need to worry? Right? Because then, and even if you're like, I don't think this is a real, your patients at some point are going to ask you about it because it's out there. So this is going to be a fascinating discussion. You're really going to be surprised at what we talk about. So join us next week. Thanks for joining us this week. If you've got questions, comments, ideas for topics you'd like to see us cover. People you'd like to see us have on the show. Shoot us an email at
[email protected]. Again, that's
[email protected]. Hope you learned a few things. Hope you'll have to answer twice. And mostly, I hope you're going to join us next week. So until then, I'm Matt Cyrus. I'm Tim Patton. I'm Laura Ferris, and we are Dermsondrugs.
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