Boosting Isotretinoin, Outsmarting Botox Resistance & Other Plot Twists

Welcome to season two of Derms on drugs and video podcast brought to you by scholars and medicine, the best educational platform in dermatology and provided to no cost to medical providers. Derms on drugs is we're cutting edge dirt meets the Edermis comedy. I'm Matt Zyres from Doc's dermatology in each week. I'm joined by my residency buddies, Dr. Laura Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh, where we use our 60 years of combined during 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 therapy and you have some fun listening. New episodes drop every Friday on scholars and medicine, Apple podcasts, Spotify and other major podcast platforms. And a reminder that we do have a video component that has the key figures and tables from the articles we talk about. This week we've got another one of our fabulous patented six pack episodes with the hottest new stuff off the literature. Dr. Ferris was adding new articles right up till the last minute. And then let's go ahead and get started. Dr. Ferris, what do you got? All right. So my first article is was in jamma dermatology, immunostimulatory herbal intake and auto antibody positivity in dermatomyocytus. This is Yang at all. So this is Vickiworth's group at Penn. Wait, what's your share? She's about to tell me that taking immunostimulatory herbs helps dermatomyocytus. No, I'm going to tell you it makes it worse. What? Can cause it? This, you know, this paper just came out, but when I was back at Pitt, Vickiworth came and she gave this lecture in rheumatology grand rounds and I went there and she was talking about this and I was like, wow, this is really like pretty amazing stuff and something that could be, I think, really easy to overlook. So when this came out, it was like current literature and I'm going to bring this up because I think we all need to have this like on our radar. So, you know, so it turns out that these, you know, immune boosting herbs that patients obviously just get it, you know, at the store with they're not really regulated and it really does turn out that they can have a role in dermatomyocytus. And they had already published that. So, you know, why did, like, so, you know, what did they show in this paper? What they did was they looked at 286 patients all with dermatomyocytus and all of them because they had seen this pattern had been screened for prior use of immunostimulatory herbs before they developed dermatomyocytus. And it turned out that 13% of them had used herbs. The median time from first herbal use to dermatomyocytus onset was basically a year, okay? The most common ones that were used, spirulina is the big one. So like, if you're only going to remember one, think about spirulina. Once I heard this, I would like go to, you know, go to get a smoothie or go look at things. Like, spirulina is all over the place. Like, you pay a dollar and you add spirulina to your smoothie. I almost started recommending spirulina because there was a study that showed it might have some benefit. They probiotic that had lactocase, a bacillus, remnosus and spirulina had some efficacy for acne. And forget that. I'm going to get rid of their acne and give them dramatic. Yeah. Don't do that. Maybe get them going the sun right after they take their spirulina to really clear it up. But now, so spirulina, 61% of the patients, that's what they took. The other one was elderberry, about a quarter and then ash goonda 11%. And then there were a few other ones that were that were in there. So, you know, the thing that was interesting here was what they were looking at was myocytus, myocytus specific antibodies and myocytus associated antibodies. And they compared the herbal intake to the non-erbal intake group. And there were significantly lower rates of antibody positivity in the group that had herbal intake associated dermatomyocytus. So, you know, this is why I thought it was important. So, if this looks like, man, that looks like dermatomyocytus, the biopsy suggestive, but they've got negative antibodies, you know, don't make sure that you're getting a good supplement of into, you know, history in these patients. So, they may have negative antibodies, but they've got the disease. So, here's what you, when I read this, I thought, hey, it's good to not have any antibodies. The antibodies probably make your atomizer worse or they're markers. You got cancer or whatever. So, the, the herbs are helping. They're getting rid of your antibodies. No, I don't think it's getting rid of your antibodies. I think, you know, antibodies, these antibodies are probably in very many ways markers. They're not necessarily the pathogenic antibody. And so, you know, it just, I don't think that it's a good thing. And you know, one of the things that they, with that I had asked her when she presented this at Pitt was, you know, what if they stopped their spirulina and it turns out that some people still do have persistent disease. So, I think it is the border. Ask it. What's that? But some people do get better. I mean, with, with anything, some people could get better. They don't have a good, they don't have a good study that I saw on like treatment resistance, right? So, you know, but I think it's important to ask about this. I think it is important. Certainly to have them stop it. There is some, you know, there are some like mechanistic, mechanistically plausible ways that this could happen. So, spirulina can increase to like receptor four activation in vitro and patients with dermatomyocytocells when it's treated in vitro with spirulina. The other one that actually has come up to not necessarily in this one, but is isoline, which is this like weight loss alfalfa-based like natural weight loss product. And that has been associated with increased levels of tumor necrosis factor, interferon alfalfa and interferon beta. So, you know, why do we need to know this? You know, one, this doesn't make people's med lists. So, you have to actually ask about it too. If it looks like dermatomyocytus, but it's not perfect and you don't see, you know, any of the auto-anabodies think about the, you know, herbal supplements. And, you know, and then, you know, counsel patients, who are maybe like autoimmune diapyces type patients to avoid these, you know, these drugs. Now, one of the, you know, confounding factors that they acknowledged in this paper is that we know that things like viral infection can also trigger, you know, splares of most autoimmune diseases or, you know, autoimmune onset of new autoimmune activity. You know, might patients have had a viral infection and thought I'm going to take this spirulina echinacea to get better and was it, was it the herb or was it the infection that they were like self-treating with the herb? So, there could be, you know, that could be a confounding factor. But I think it's important to know, especially spirulina. And, you know, when you've got like young kids or, you know, children who like to get smoothies with all kinds of herbal things, I'm like, avoid spirulina. Okay. All right. I like it. Spirulina. Got to ask about stuff that's cheap, that's easy, and I'm a big fan of cheap and easy. Okay. All right. Dr. Patten. Dr. Patten, what do you got? My first six pack papers titled from inflammation to circulation, biologics reduced clot risk in hydrodynamic subvertiva by alam et al. In the November 2025 edition of the International Journal of Dermatology. I guess there was a 2024 JAD publication highlighting increased risk of venous thrombone and bellizum in H.S. patients. I can't say I specifically remember, but sure increased inflammation in H.S. and that leads to clots I can buy it. So these authors wanted to see if biologic therapy for H.S. had any effect on clotting. So they went to trinetics. Are we, do we like trinetics? Are we anti-trinetics? Are we still undecided? I mean, I'm becoming slowly anti-trinetics. I think it's when I like I said, I tried to do like a little bit of a study in it. It was just so the way they report the data that H.S. one you did where it was like, no, everybody, not everybody who's taking this drug is like, I couldn't, I couldn't, I can't figure it out. I can't figure it out. Yeah. Yeah. Too complex for math. If I can't figure it out, then it's not figure out. I know. It's not, it's not legitimate. Fares were you with trinetics? No, I, I am, we just got it at UNC. So I'm actually like when I get some free time, I want to learn it a little bit better, even better find a med student who will learn it a little bit better. And I want to play around with it. All right. Yes. So I'm excited for it. Okay. Well, once you're really running along with it, Fares, you're going to tell us if it's baloney. And obviously it's not baloney. It's real data, but just is the way the data is sifted. Like, can you make it? Like, how much do we trust it? Do we say, hey, yeah, there may be something there or I'm just going to ignore this, like Fares, right? Fares were done with. Yeah. Yeah. Completely. Yeah. Poppininess vaccine reporting side effects. Yeah. We're like that. Yeah. Okay. So trinetics hasn't reached that point yet. So still hope. All right. There were over 15,000 HS patients who received biologic therapy. This included the cannercept, that aluminum map and flicks and maps, Seki kinamab, Ustakinimab and even Anna Kinro, which I thought that was interesting. Bimmy was not on the list, I guess, because it was newer. These were matched with 1500, no, 15,000. HS patients who had not received biological therapy in the odds ratio for both venous thromboembolism and pulmonary embolism were low in the biological group odds ratio of 0.56 for VTE and 0.61 for PE. But that's in the table, I forget which table it is, but we'll have it on there. But the HS patients on biologics were just kind of like healthier overall. They had lower odds ratios for diabetes and chronic kidney disease and elevated cholesterol. They had an odds ratio of 0.4 for tobacco use. It seems that the propensity score matching like should have included that they just kind of did like age race. Maybe that would be harder to do. I don't know. I've never done trinetics. So yeah, the less you match on the more like matches you can get, but the less similar they'll be right. And so then you can do like logistic regression to try to adjust for all these different factors, but it's like then you're getting into complicated statistics. I mean, I think HS patients often want to go on biologics. It's not like you have to sell them on it. I will continue to prescribe it. I don't know them going to be strongly suggesting that hey, there's all these added benefits. You won't get blood clots if you go on biologics. There was this paper. And one of the biggest reasons why we looked at this with metformin, right, HS patients on metformin. I also think was trying that accident was like decrease risk of cardiovascular. I mean, it was like these really impressive numbers. But the problem is when you have patients on these therapies, let's say they've gone through every single biologic that there is and they're not any better. I can't see myself saying, well, look, you need to stay on it because of this decrease risk of clots that I read about in this one paper. So I don't know. I don't know what to make of the paper. I don't think it's, you know, like I said, you try biologics patients want to oftentimes go on them. I don't know that I'm going to be trying to sell patients on. There's other benefits aside from disease control. That's actually this super interesting question to me if the clinical efficacy of a biologic say we're talking about psoriasis where we know that biologics reduced cardiovascular morbidity mortality or they seem to. I don't know that we know that but we think yes, we think so that the efficacy predicts that's an impact on risk of this other stuff. So if it right. So if it doesn't get your HS better, it would be intuitive to me that it's not really going to help that much with your cardiovascular risk because it's not really reducing your inflammatory burden. Right. Kind of a deal like that. The other thing that was interesting fascinating to me looking at this was I still think that there is a huge component of no matter how well you try and match it. Somebody who is capable of getting on a biologic is different from somebody who's not capable of getting on a biologic like that is a marker for a level of health consumer sophistication. Right. Being able to get on a biologic and that a lot of they just they mentioned that confound you know those patients are coming into your office you're monitoring them much closer. They're seeing just doctor they're getting doctor care more than the patients not on the body. So all of that's going to benefit. Yes, it's not just the biologic. Yes, and even beyond the care that they're getting as part of the biologic in the HS they're just better healthcare consumers. Like their answer in their phone their understand how their insurance works they you know whatever they're just different. So even if you match them based on interaction with the healthcare system you'd still be like well the people who get on a biologic or it's a marker. Yeah, you know, okay, so good stuff. Let's jump over to my first two so I I am to AD not ADD Asian. I'm too superficial to go in depth into one thing. So instead I'm going to go shallow into two. Okay, so my two articles here for this first part number one the efficacy of combined oral isotretinone and desaloratidine or levosatyrzine versus isotretinone monotherapy and treating acne vulgaris and systematic review and man analysis randomized control trials. So I've been talking about this for at least 10 years. We're now up to in this they found 10 studies 675 people in randomized trials. Generally it was relatively lower dose isotretinone and then we usually use more like 20 milligrams a day or 0.25 mix per gig which is again about 20 milligrams per day. Although some of the studies use normal dose isotretinone but may take away here. This is super cheap and easy. So first all that's been studied is desaloratidine and levosatyrzine but loratidine gets metabolized to desaloratidine. So you should be able to use loratidine which is as close to free as you could possibly free and totally save as you could possibly get. And by adding desaloratidine to isotretinone they had 8 fewer inflammatory lesions at 12 weeks compared to people getting the same dose of isotretinone and they had a 50% reduction in the probability of getting key lightest. And so it is a thing to me like it's so cheap and easy. We probably ought to be like hey and by the way get some generic loratidine and start taking 10 milligrams of loratidine a day together with the isotretinone. Does it actually do anything or not that's clinically meaningful don't know but it's completely safe and extremely cheap is kind of like. I read these studies and like I know that's out there I'm always like yep I got to do this it's like just the habit right like it's so terrible the habits that we have that make us not do this like a couple times I've done it when somebody's complained about the tolerability or why is it not working why am I not respond you know you sometimes have those people you're like actually been on six months of a big per keg of isotretinone and like I feel like you're not budging so like I'll pull it out when I need something to get them through this the key lightest or to get them you know a little better efficacy but we should just start like putting it in our regular counseling right the script or whatever put it in your dot phrase and epic if you're an epic user like we just got to we should just do it it's like it's silly. There are two things we should be doing everybody with the we started I said treetone should be going on how to make a three fish oil good data that that reduces key light is in nosebleeds and loradadine the fish was harder to take their bigger pills they're more expensive but the loradadine is just so cheap and so easy even if it makes a little bit of a difference but yeah it's it's you know remembering to do it right and and you're trying to get you try to get them enrolled in i pledge trying to do talk about this talk about that and the blah blah blah it's like one of those things that like how much stuff can you throw into the visit you know is is a big part of the way you think about it yeah alright my second thing there was a quick hitter to stay kind of in the acne a form distribution things it's what's called ticked TYK ED off by rosacea in a string case series of rosacea associated with do kravacit nibb basically was just a case series of seven people who had pretty classic popular pusher their rosacea show up once they went on do kravacit nibb when I looked at these patients it actually looked to me even more like demodex than it did like typical popular pusher the rosacea and we just talked about an article a few weeks ago from the inflammatory bout disease literature where jack inhibitors caused like lots of people to get demodex infestations so although questionable if a tick you know is tick inhibitors having a jack inhibitor I don't know but just an interesting thing to have in the back of your mind if if you have a patient you start on a tick two inhibitor and they get something that looks like rosacea it could be from the tick two inhibitor and these patients had to come off of the drug they were bad enough that didn't be enough of their options that kind of stuff but fairs is this something that you you know flickular disorders are they like a real thing with with tiktus and psoriasis? Yeah I think you can see some of the jack like like jack knee type stuff with tick two inhibitors I have seen that before Tim have you seen that? I don't have too many people on tiktus and but the people I have that's not an issue yeah I mean I wouldn't say it's like common but I you know what I think is like did they they didn't look for demodex in these patients I did not see that they did demodex and I think they did like demodex preps in them so it would be interesting like I've seen patient you know what I mean like I've seen patients and like someone case like a guy who's on a course of prednisone and just got like florid demodex right and like we see that happens sometimes and I mean that's an easy thing to treat. They mentioned in the paper that if you decrease aisle 13 that's actually bad in terms of you know demodex population apparently aisle 13 helps us keep demodex growth in control but I'm not really aware of demodex being an issue with you know any of the drugs that we use that block in 2007. that was my leading theory for the Demadek for Dupy conjunctivitis. And then when Dupy red face came out, was it's, you know, Demadek's as a parasite, I/O13 is involved and it's in the label, we should be worried about parasite infections. These drugs are letting parasites run wild, but treating as dead, and there were actually a couple of publications hypothesizing this, but it hasn't played out as like that the I/O13's actually, I/O13 inhibitors actually seem to impact Demadek's at all. - I can remember one of my Dupy patients in Pittsburgh having horrible Demadek's after I started. Like, shit, bad E.D. never had rosacea came in, horrible rosacea, it was all like fluorid Demadek. So, and I was like, oh, this makes sense. I feel like I've had that, I've seen that a couple times. So it would fit. When the red face that started to come out, people really thought about it then as well, but I think it does happen, but the red face is usually more maliceasy and driven than it is Demadek's whenever we see the red face with Dupy. - I do think the pearl is like, particularly if somebody's on a new immunomodulatory are on an immunomodulatory drug. If all of a sudden they've got papula postularization, just like for Demadek's. And, you know, if you can treat that, and I did with this person, she was great, treated her through it. The Dupy was life saving for her bad E.D. Like, look for it 'cause you might be able to treat through it. - What's your demo next go to Ferris? - So I like oral Ibermectin. You know, I do it once a week for four weeks. I also do like the rosacea triple cream with Ibermectin metronizol and azaleic acid. - Yep, I do, I weekly Ibermectin combined with oral metronizol. There was a study like 15 years ago looking at this and it was more effective, substantially more effective than either one by itself. I think Ibermectin usually works, but when you put Ibermectin and metronizol, you get so it's Ibermectin, you know, every week. And then the metronizol, just, well, the study was 250 milligrams TID. You start it the same time you take your first dose of the Ibermectin, you do that for two weeks and then you're done and you transition them over to the triple cream. The other thing with Demadex is you wanna put the topicals on at night before they go to bed because the Demadex come out of their pores and walk around on the surface of their skin at night while they're asleep. - Is this a theory or is this a proofing? - No, I've seen it. - I think of that as true. - You think of that as true. That does not mean it is. - All right, I'm gonna look at it while you're in prison. - I've got one more pearl for Demadex, for you that I learned accidentally. If you'd like, when people, you cannot clear it, five floor uracel, give 'em FUdex. - Oh, right, it's toxic. - I learned that I had an old surgeon who was in Pittsburgh, who I'd given him topical FUdex and he come, like three months later, comes up into my office. Like I'd like to see Dr. Ferris and he was the kind of person who could do that. And he's like, this is my secretary. She had this bad rash. I gave her my cream. She's better, you need to investigate. It's like, oh, they're her chart. She had rosation, Demadex. He gave her FUdex and of course, it's like a, you know, intercalating agent. It's like if I bathed all of us in five floor years, so we would die too. - We would care too. - Yeah, so it's chemo, it's chemotherapy. But I actually have tried it a couple times when I bet people had recalcitrant Demadex and it's helped. So, all labeled. - You've said a lot of smart stuff over the years. That's my favorite thing ever. Five FU for Demadex right there. Oh, that's right. - That's right. - Okay. - That's right. All right. - All right. - We heard it here. - All right, all right, all right. Let's move on to our next article. - This is me. Okay, I'm back with one of my favorite drugs because it was back in the New England Journal of Medicine or one that I'm most excited about. This is oral Icochricinra for plaque psoriasis in adults and adolescents. So this was New England Journal of Robert Bisonette at all, New England Journal of Medicine. Iconically phase three studies. So Icochricinra, this is a targeted oral peptide that you take daily that blocks the IL-23 receptor. So, 684 participants, adults, they had to be adults or adolescents 12 or older, so about 10% of the people in the study were adolescents, the rest were adults, randomized two to one. Icochricinra, 200 milligrams once a day or placebo. People were excluded if they had failed or had an adverse event with the IL-23 targeting biologic in the past. They took the single tablet with water. They had to take it after waking and no food for 30 minutes after. But one interesting thing was that if they had, for adolescents who couldn't swallow tablets, they could actually just dissolve it into water and drink it. So I thought that was kind of interesting just because it's like, you know, kids don't like needles, kids can't swallow pills, what do you do with them? So I thought that was kind of interesting. So who were these patients? You know, BMI on average was 29 Pazzy scores of 19 to 20, which are high, but not as high as we used to see. They also did look at scalp disease. So, you know, the percentage of patients who had scalp disease was pretty high. And it was, and their IgAs were, you know, predominantly three, some fours. And say, okay, so co-primary endpoints, Pazzy 90 IgA zero or one at 16 weeks. So what did they see at week 16? IgA zero, one clear, almost clear. And 65% treated with Icochirkinra versus 8% with placebo. Pazzy 90 and 50% versus 4% with placebo. Pazzy 100 rates, you know, the thing that we really love to see 27% of treated patients versus less than 1%. Now, this was at week 16. And, you know, IgA zeroes were kind of similar. You know, if we look over time, 'cause they did study everyone out for 24 weeks, yeah. - Well, so when I was looking through this, which shockingly I looked at it ahead of time, are we now, are they now commonly reporting IgA zero ones as an outcome measure in psoriasis? We were, like, is that now considered on par with Pazzy? - Yes, yes, the FDA likes IgA zero one. And do you know, so an AD, I'm very comfortable saying, what IgA zero one means, IgA zero obviously, you don't have anything, IgA of one in AD means barely perceptible to a trained observer. We are trained observers, so it's barely perceptible to us, not perceptible to the patient. So somebody who's got an IgA of one, the patient says, I'm totally better. And we say, "Ah, you're not quite totally, "it's tiny bit of a big thing there." How do you clinically think of IgA one in psoriasis? - So it should be static, and it should be that erythema is, you know, barely perceptible, minimal elevation and minimal scale. I mean, IgAs in psoriasis, we don't like because they don't take into account body surface area. So, you know, to me, it's like, they're like, wow, look at that, you're so much better. Do you have any psoriasis? And it's like, you know, there is a little bit here in here and here, I'm like, okay, that's an IgA one, right? As long as those are not significant appearing plaques. If you really had very, very thin light red plaques over 90% of your body, I'd have a, I'd be our press to call you IgA one, even though if you're a sponsor of a study, I'm on, I know that it doesn't involve the body surface area. So, I looked it up while you were, and there is a report. So, you were very prescient in 2014 in the journal Cornia. They reported that 5FU was highly effective against Demodex Blyphoritis. - Wow. - So, you, okay, don't use it on the eyes though. I'm not recommending that. - I know it was eye drops and they was a, - Okay. - But the main takeaway was, so 5FU did kill the Demodex. So, good first, I'm impressed. - Thank you. - Okay. - Thank you. All right, so yeah, so that's that. I thought you were gonna be impressed by my IgA scoring. Okay, other like key things, adolescents, again, there weren't tons of them. Pazzy 90 rate was 70% versus 14% on placebo. So, I thought that was good. And then, you know, safety stuff was mild URIs. Okay, key things that I thought were really interesting here. 48 patients had latent TB infection at baseline. And of those 20 of them did not get treated for it. So, you could go into the study with latent TB, not get treated and none of them developed TB activation. Now, I get it's only 24 weeks, but I think like this may be a drug that we don't actually have to do TB testing for. So, I thought that was like one of the more interesting things. So, there wasn't a company editorial, there, you know, thing was, yes, that's great. Like 2% to 3% of the population has psoriasis. They don't like it. What are we going to do about the fact that this is going to be incredibly expensive? So from 97 to 20, 25, spending for psoriasis drugs in the US increased by more than 2,000% in constant dollars. That's not adjusted. And the average wholesale price for the first year of therapy for most biologics exceeds $100,000. That is, again, micrometics red book. That's not including all the kick, whatever rebates and everything. But interesting study, interesting to me, the latent TB not being treated. I've never been able to do that in psoriasis study. So all right, Ferris, we've talked about a coach or kinder number of times now here on terms on drugs. And I know that you still nobody knows the actual answer to this. But where do you think it's going to fall efficacy-wise compared to-- does this give you any new information on where you think this drug's going to fall efficacy-wise, comparatively to our existing therapies? Yeah, I mean, it's going to be better than a Promoelastic rabbit, a Cittnib. It's probably going to be around the Stalara-ish efficacy. It's going to be better than-- I'm going to put it between Stalara and not quite trimphaya. OK. All right, Ferris. And oral and hopefully no labs and the whole thing. Do you have a no? Is there a pedophadate yet? Do we have an idea? I do not know. That does not mean that there's not one. I don't know. And in this study, it was once daily or twice daily. This was once daily. All right. And you do have to take it not with food or something. Yeah, so don't take it. It's fault water. Don't eat for 30 minutes. So again, an absorption thing. It's not like-- Yeah. Man, it's not going to hurt you. It's not a safety thing. It's an absorption thing. Yeah, it's an absorption thing. So you take it first thing in the morning before you-- yeah. OK. OK. There is no. There's similar data with TB in the biologics, isn't there? I mean, not that it was part of a trial. But definitely-- Not both, but definitely in trials. But yes. But definitely reports of latent-- and when we say latent TB, we're saying-- A positive amount of-- Their quant gold was positive. Their chest x-ray was negative. Yes. OK. Right. So I mean, I think that-- I don't know that I co-tracinarize safer than the biologic that block aisle 23. No, I don't know. I don't know if you're afraid of data. It's what are you going to get in your label from the FDA? Right. Yeah, right. Dermatologists do not like to check blood work. And you would not have a leg to stand on to put somebody on trim fire or sky-rizzy without a quantifier on gold. If-- You're a little bit too late. I'm sure it's going to be a little bit too late. If they developed it, you wouldn't-- I mean, it's in the label. You would not-- If they develop TB, A insurance won't let you do it, and B, if they develop TB, you would find somebody who would testify against you. This is on the right. If it's not in the label, and insurance cannot require it, and you can actually give patients a drug without having to check any blood work, that's going to make a lot of things really easier, a lot easier. I still say that is the whole reason why-- that has been behind much of the success of a Tesla. So-- Absolutely. Yeah. Absolutely. All right. Pat, what do you got? My second six pack was titled a Primalass for oral eucosal predominant resistant, pempagos vulgaris, a promising adjunct of treatment by Zangat Al. In the November, 2020, 2025 edition of oral diseases. Most of the authors are from Wuhan Hospital, which I think-- I would just say I'm from somewhere in China. People-- I'd be like-- Like the harbor people are like, where are you from? Boston? Where'd you go from? Yeah, right. I'd be like-- China. Somewhere in China, like the middle of it. You've never heard of it. Although one of the authors was from UNC. Oh. Dr. G. Liu, in my department. Yes. Cool. So Dr. Zang, the lead author, had published some other stuff about pempagos in a Primalass that didn't appear to be effective for moderate to severe PV, could be used as monotherapy for PF. There was a patient with IGA pempagos that had apparently a decent response. So definitely some sort of mixed evidence in the literature. But it kind of suggests certain phenotypes may respond better. I've definitely had pempagos patients that present with oremicosal disease exclusively, or oremicosal disease and skin. And after corticosteroids and retoxin lab, like skin lesions get a lot better. Orel disease also improves. But they continue to have these nagging erosions and gingival sloughing. It's like they're better, but it's not like-- the orel disease goes into a complete remission. And that's kind of tough, because what do you do in that instance? Like they're way better. It's not life threatening at this point. Do you go aggressive? Do you keep giving me more retoxin lab at IVIG? I don't know what to do with these patients. They can be tricky. So this was a prospective non-randomized study. Five patients, they had oral predominant PV. Some of them had skin, but it was pretty limited. And they continued to have active oremicosal disease despite 12 weeks of prednisone plus minus mycophinolate. Retoxin lab is like kind of standard of care, but none of the patients-- like they weren't called recalcitrant, but yet they hadn't received retoxin lab. So I thought that was a little bit odd. Anyway, each patient was then treated with a premalast standard dosing that we do, building up to 30 milligrams twice a day eventually. And prednisolone 0.5 makes per kick. Figure two at a bunch of line graphs, detailing improvements in the pantheogous disease severity index, Desmoline 3 and one titers. Prednisolone dose was able to be decreased in all the patients. It's probably worth a try. I mean, when patients are combined with systemic corticosteroids, it's always hard to figure out. And if you're not significantly decreasing Desmoline 3 antibodies, like the change in the antibody titers just really weren't that impressive. There was maybe one patient where Desmoline 1 was a huge difference. But the Desmoline 3, it's kind of like maybe a little bit less than this guy stayed about the same. So if you can't decrease antibodies, how effective is a medication going to be for pantheogous? We always kind of learn that if the antibody's there, it doesn't have to activate complement. It just binds to Desmoline 3 and that's sort of what triggers the disease. If you're not getting rid of the antibodies, can you really effectively manage pantheogous? There was a few sentences in the discussion about how a premalast may strengthen the cytoskeleton, counteracting the effects of antibody binding. I mean, right, a premalast, and we would probably use Rolf Luma last because they-- I wish we did have a Rolf Luma last sponsor. It's just not going to happen, is it? Because generic. Oh well. But these are tricky patients, like I said. And Rolf Luma last is easy to give, tolerated relatively well. I don't think it's unreasonable to try. I just wouldn't be surprised if the response wasn't fantastic, because they did give the patients prednisolone at the same time. And that's always hard to tease out what the non-prednisolone treatments are actually doing. And there is definitely data that PDE4 is inhibition is good for your cytoskeleton. So I could certainly at least buy that it's working by protecting the cells a little bit from the effects of the antibodies rather than getting rid of the antibodies. Yeah. Like that's viable. Like I would see it. OK. Do you think you'll be using Rolf Luma last early in Pemphagos at all? Is there any chance of that or is it-- No, really where I see this is just in this case. I was talking-- I think Donna Colton was on our show earlier. And she was talking about what do we do with these patients? They don't really have high titers, but they continue to have a world disease. I talked to her. She had actually been starting like intreligional retoxamab just in the mouth, maybe trying to get some resident B cells out of the way. And maybe that's what's causing disease. So no. I wouldn't start this initially. But for those patients where they just have this persistent-- every time they brush their teeth, they're bleeding. Or if they eat a certain food, it's like, ah, I really hurt when I ate this particular food. And oral erosions and ulcers-- that's just miserable, right? At this ulcer, it makes your life miserable for the one or two weeks that it's there. Just imagine that being like constant. It's a lot of morbidity, even though you say their life because they came and covered in blisters or talks about a prednisone, they're way better. But they're really miserable. So I'm going to try it. OK. All right, fair. All right, let's jump onto my last two. So first one, fascinating to me. So reversal of partial botulinum toxin A resistance, Following Janice Caini's inhibition with tooth is Cidinib, a C-C-C-S-E-R-E. So there's two cases of people who had been getting various toxins, and the toxins were working less and less. By the time it got to the point of these C-Series, it was only working for three weeks, and then they gave them Tofacidinib for a couple of weeks, and gave them more toxin and lasted for three months. So the problem with this, right? Obviously from the first idea of like, are we going to have somebody potentially toxic drugs so that their Botox will last longer? It mechanistically truly doesn't make any sense, because if the toxin is just being neutralized by an antibody, if you put them on a jack inhibitor for three to six months, sure, I could see your antibody titers going down, but this just, it shouldn't work. It shouldn't have any impact on the antibodies within a couple of weeks, but it was just interesting and something that I was like, "Oh, I want to talk about that on the podcast. Could we improve our cosmetic injection outcomes by giving people jack?" And now those drugs don't really be a reason to have them if they can help make Botox last longer. Finally, just not be resistant to it, right? It didn't really make it. It wasn't like, "Oh, it's not making it last longer." Well, it was longer in the patients in whom it was only lasting three weeks, but it didn't get right in normal people. It wasn't like it made it go from three months to six months or six months to nine months or something. Yes, I would agree. Yeah, this was all done in Bayroot, Lebanon. I mean, I'm trying to imagine trying to do this here. And they put people on methotrexate. One person was put on methotrexate. Yeah, to see if they could get their Botox to work better. It's trying to get that through insurance. I thought the woman that got methotrexate had out Peeche, Ariana, and that's why they were giving her methotrexate. And that's why she actually got the jack too. Yes, that actually was true. I just saw the methotrexate and I was like, "This is kind of crazy stuff." Yeah, that doesn't make a whole. But just letting our listeners know it's out there now, in case a patient comes. It's the kind of thing now that I could see a patient looking up. Botox doesn't work in me anymore. What can I do? They come in wanting to be on Zelljams. The other one was just something that I think Derms, we need to just be very aware of. I don't think it's anything we're actually going to do. But it was just interesting. So Scalp cooling therapy in chemotherapy induced alopecia, addressing variability in cooling, duration, and efficacy. So the basic idea here, and this has been around for quite a long time, that if you put like a cooling cap on somebody's head before the chemo starts, and then while the chemo's being infused, and then for a little while after they get the chemo, you can really reduce the severity of the chemo induced alopecia. The assumption, of course, is at least mine, is that you're restricting blood supply at the Scalp. And so as a result, you're not getting as much chemo that's going to be toxic to the rapidly proliferating hair cells. This really was just back to the old idea that it's a reasonable assumption most of the time to say that more is better, but it's actually not the case here. So first two different main types of chemo used in breast cancer. So there's taxains and anthrocyclins. This is cooling is highly effective with taxains. So like 90% of women in breast cancer. So in these are using the cancers of the breast cancer too, but the studies are all in breast cancer. Basically 100% of people who get a taxain will lose all their hair when they get treated for breast cancer. But if you do the cooling, about 90% of them will protect the majority of their hair. But that, you know, some of these protocols, they're doing it for like four hours after your infusion. You're supposed to sit there with the cold thing on your head. Really, the data is 30 minutes before the infusion, then 30 to 45 minutes after the infusion, seems to be just as good as doing it longer. And then the other one, anthrocyclins, it's much less effective. So again, about 100% of people will get severe alopecia with an anthrocycling. These cooling things. So 90 minutes of post infusion, again, you do probably 30 minutes before in the 90 minutes of post infusion reduces like severe total alopecia down to 50% and if by 50% and if we do it for 150 minutes, two and a half hours, instead of an hour and a half, it reduces total alopecia by 70%. However, the frequency of North needing to cover the scalp with something was still 70%. So meaning it prevented people from going like completely bald, but made their hair thin enough that like they still were wearing a wig or wearing a scarf or a hat or something like that. So the anthrocyclins that take away is it doesn't work as well for those, but still is worthwhile. And it's just an interesting thing and something that I've actually talked to a few friends who, you know, got breast cancer, was like, oh, make sure you talk to your oncologist about, you know, doing the scalp cooling so that you don't lose your hair. It really did make a very big difference for them in their quality of life. So it's just, it's definitely worth us's germs knowing that this is out there. And I thought it was just interesting that it wasn't necessarily the case that more was better. Take away. Yeah, I think these are actually covered by insurance now for women undergoing came out therapy for breast cancer. I think in some places it's covered. So do the cancer centers typically provide these devices or is it something that the patients have to kind of get on their own? No, I think it's a device that they literally have in the infusion center because you're you're there in the, it has to be be it's not like you don't have to do it like every day. So do they offer it to every like or is it, I'm just surprised that a person would be like, yeah, I don't want that. When isn't everyone getting this then? It's a good question. So let me end them. I'm going to AI that right now does every breast cancer patient get offered scalp cooling and is it covered by insurance? I can literally feel the AI making me dumber as we speak. Yeah. Yeah, no, I think that well, I don't know the coverage, but I think it's good for patients to know to ask about it and it's good to have actually like, you know, data to say, you know, how long to do it. I think people actually have to get them have to get them like as their own device. I don't think that it is like here here's your IV and here's your cooling camp. Like I think people have to actually have to have them. So see, let's see, or does it need a prescription and all that I believe. Okay. So interesting. Let me see what AI agrees with Ferris or not here. Let's see here. Depends to get their own device. It is the center. Have it. Come on. I'm just going to ask you that. How many times in your life do you have you guide then guided by the theory that, you know, if less is good, more is better. I feel like, yeah, I feel like this is like one of your guiding principles. Anyone who knows you well, it explains a whole hell. It does. So most patients use a device provided by the infusion center, but some systems require patients to rent or purchase their own cold caps and bring them to treatment. Yeah, looks, I mean, it's probably site. It looks like the one at UPMC. I mean, they have a whole page here. They probably mark it up. Yeah, we offer cooling therapy to people receiving chemo. Okay. Okay. Interesting. All right. I want to thank our listeners for joining us this week. I hope you learned a few things. We hope you laughed once or twice and mostly we're hoping you're planning to join us next week. Till then, I'm Matt Zyrus. I'm Tim Patton. And I'm Laura Farris and we are Derms on Drugs.