Rashes, Pre-cancers, and Cancers – we've got the answers!

Summary

Podcast Summary: Derms on Drugs

Episode: "Rashes, Pre-cancers, and Cancers – we've got the answers!"

Date: October 3, 2025
Hosts: Dr. Matt Zirwas (A), Dr. Laura Ferris (B), Dr. Tim Patton (C)

---

Overview

This energetic episode features the dermatology trio—Drs. Matt Zirwas, Laura Ferris, and Tim Patton—discussing noteworthy recent studies and clinical pearls on rare skin cancers, supplements, eczema therapies, seborrheic dermatitis, actinic cheilitis, and the evolving science on the skin microbiome in atopic dermatitis. True to the podcast’s promise, the group injects banter and candid opinions, making for an informative yet entertaining session.

---

Key Discussion Points and Insights

1. Merkel Cell Carcinoma Surveillance with Antibody Titers

[01:10 - 12:35]

• Study: Gunnell et al., JAMA Dermatology (Paul Nghiem’s Seattle group): Long-term surveillance data using Merkel cell polyomavirus (MCPyV) oncoprotein antibody titers (AMERK test).
• Core findings:
  • About 80% of Merkel cell carcinoma (MCC) patients harbor the polyomavirus.
  • Antibody presence = better recurrence-free survival at baseline ([05:52]); ideal is to have a positive but low titer.
  • Falling or negative titers: Strongly predictive (>99% NPV at 3 months) of recurrence-free status ([06:22]).
  • Rising titers: Signal substantially increased recurrence risk (up to 68% in 2 years, HR ≈50:1) and predate clinical/imaging recurrence by ~4 months ([06:22, 09:04]).
  • Circulating tumor DNA (ctDNA): Even more ominous if detectable—27-fold increased recurrence risk ([08:46]).
• Clinical Takeaways:
  • Monitoring titers can spare patients unnecessary scans if falling/negative; crucial to draw baseline within 3 months of diagnosis ([11:10]).
  • Sentinel lymph node biopsy is essential ("If you remember nothing else, remember that" – Ferris, [12:05]).
  • MOHS not first-line unless multidisciplinary; always consider surgical oncology.
• Quote:
  • “If your titer is falling and you go to a negative titer, you could potentially avoid getting…CT or PET/CT scans.” (Ferris, [06:22])

---

2. Does Collagen Supplementation Work?

[12:36 - 19:47]

• Meta-analysis: Myung & Park, Am J Med, Sept 2025—RCTs of collagen supplements for aging skin.
• Findings:
  • Collagen improves hydration, elasticity, and wrinkles—but only in industry-sponsored and low-quality studies ([15:04, 15:47]).
  • Fish collagen in drinks best (not pills/powders), per sub-analysis ([15:09]).
  • Non-industry, high-quality studies: No benefit ([15:47]).
• Hosts’ reactions:
  • Widespread skepticism (“I am telling my patients collagen supplements are very likely a waste of money.” – Patton, [15:47]).
  • Still, minimal downside if patients insist, and price is key; suggest cheapest options ([19:18]).
• Quotes:
  • “If the study was a high quality study, it did not show any benefits.” (Patton, [15:47])
  • “Go with the cheapest.” (Patton, [19:42])

---

3. New Therapies for Chronic Hand Eczema: Ruxolitinib and Delgocitinib

[19:48 - 30:57]

• Study: Ruxolitinib cream (Opzelura) vs. placebo for moderate-severe chronic hand eczema—excluded classic atopic dermatitis ([21:01]).
  • 53% IGA success rate vs. 11% placebo ([24:44]).
• Delgocitinib (Zupco/Enzupgo): Lower raw % in its trial, but strict endpoint and different population—“truly can’t compare” ([27:57]).
• Key insights:
  • “Chronic hand eczema” = often AD + irritant contact component ([22:24]).
  • Steroids can worsen barrier—JAK inhibitors likely avoid this ([24:57]).
  • No reason to chase multiple indications for drugs with overlapping domains; treat by best access ([26:54, 28:06]).
• Quotes:
  • “Topical steroids make irritant contact derm worse…Opzelura and Zupco don’t have that adverse effect on the barrier.” (Zirwas, [24:57])
  • “Both work…It ought to be which one’s easier to get.” (Zirwas, [27:57])

---

4. Oral Isotretinoin for Seborrheic Dermatitis

[31:24 - 36:19]

• Study: Demirbas et al., JAD (Turkey)—retrospective, 10 vs. 20mg daily dosing, 3–4.5 months.
• Findings:
  • 20mg dose = better control, higher patient satisfaction, less recurrence at 1 year ([33:31]).
  • More adverse effects with 20mg (notably myalgia, nosebleeds), though dry lips/skin higher in 10mg ([34:00]).
  • Benefits largely while on drug; recurrence is common after stopping ([35:06]).
• Bonus Clinical Pearl: Isotretinoin effective for sebaceous hyperplasia—higher dose, short course yields long-term benefit ([36:04]).

---

5. Best Treatments for Actinic Cheilitis

[36:22 - 43:04]

• Meta-analysis: Al Fartsi et al., Biomedicines, Aug 2025.
• High-efficacy options: CO₂ laser & imiquimod show best clearance and recurrence rates ([38:12]).
• Practical challenges: CO₂ laser rarely available; imiquimod regimens often too harsh, causing severe reactions ([39:26, 40:07]).
• Host practical approach: Use cautious, slow-start regimens if needed; cryotherapy for tolerability (Patton's real-world experience, [41:11]).
• Quotes:
  • “If you use field therapy on the lip, it is an absolute disaster…absolute disaster.” (Patton, [39:26])
  • On practical management: “It’s so tailored and individual with actinic cheilitis.” (Ferris, [42:35])

---

6. Imiquimod for Lentigo Maligna & Other Quick Studies

[43:10 - 47:43]

• Imiquimod vs. Radiation for Lentigo Maligna: Imiquimod 5% (up to 5 days/week for 12 weeks) gives ~92% success, especially for nonsurgical candidates—frequency titrated by patient tolerance ([43:10]).
• Discussion: Options must be individualized, balancing surgery, radiation, or topical approaches based on patient health/goals ([44:28]).
• Other brief updates:
  • Apremilast showed modest benefit for central centrifugal cicatricial alopecia ([47:07]).
  • Ongoing advocacy for oral roflumilast: “$6 a month on Mark Cuban’s Cost Plus Pharmacy...works just as well as apremilast” (Zirwas, [47:43]).

---

7. Skin Microbiome & Atopic Dermatitis Targeted Therapies

[48:18 - 53:39]

• Study: JID commentary—comparison of JAK inhibitors, IL-13 pathway biologics, cyclosporine, and steroids on skin flora ([48:18]).
  • Dupilumab (Doopie) and JAK inhibitors improved skin microbiome (esp. staph reduction); cyclosporine & steroids did not ([48:18]).
• Quorum sensing: Once staph density is high, bacteria coordinate and trigger more aggressive pathogenicity ([50:27]).
• Clinical recommendation: For AD patients with recurrent infections, IL-13 pathway agents might offer special advantage ([50:41]).
• Quotes:
  • “Getting rid of the staph isn’t just because the disease got better—the drug does matter.” (Zirwas, [50:41])
  • “IL-13 inhibition...helps to get rid of staph.” (Zirwas, [50:41])

---

Notable Quotes & Memorable Moments

• Merkel cell antibody test:
  “If you remember nothing else, remember that [sentinel lymph node biopsy]” (Ferris, [12:05])
• Collagen supplements skepticism:
  “Pills and powders, not effective. You need to take collagen drinks...like fish collagen soda...disgusting.” (Patton, [15:09])
• Hand eczema drug choice:
  “Both [JAK inhibitors] work...should be which one’s easier to get...” (Zirwas, [27:57])
• Actinic cheilitis field therapy:
  “If you use field therapy on the lip, it is an absolute disaster.” (Patton, [39:26])
• Microbiome insight:
  “Quorum sensing: Once there’s enough of us, let’s go wild.” (Zirwas, [50:27])
• Podcast culture:
  “There’s a History of Rome podcast....I listened to the whole thing and then started it over.” (Patton, [51:17])

---

Timestamps for Key Segments

• [01:10] Merkel cell carcinoma antibody titers and surveillance
• [12:36] Collagen supplementation and industry bias
• [19:48] New hand eczema therapies: Ruxolitinib & Delgocitinib
• [31:24] Oral isotretinoin for seborrheic dermatitis
• [36:22] Actinic cheilitis best treatments
• [43:10] Imiquimod for lentigo maligna; minor studies round-up
• [48:18] Microbiome and atopic dermatitis targeted therapies
• [52:54] Clinical “itch” pathways and effect of different agents

---

Tone and Conclusion

The hosts deliver a fast-paced, insightful review of “six pack” new studies in dermatology, blending clinical pearls with dry humor and friendly jabs. Key takeaways: evidence must always be scrutinized for bias, the best drugs are often the easiest to access, and practical management beats perfection in complex real-world patients.

---

For feedback or questions: [e-mail]
Next episode drops Friday!

---

Transcript

[A]

Welcome to season two of Derms on Drugs, a video podcast brought to you by Scholars in Medicine, the best educational platform in dermatology and provided at no cost to medical providers. Germs on Drugs is where cutting edge derm meets or miss comedy. I'm Matt Ziers, and each week I'm joined by my residency buddies, Dr. Laura Faris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh, where we use our 60 years of combined derm experience to discuss, debate, and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of derm, and you'll actually have some fun listening. New episodes drop every Friday on Scholars in Medicine, Apple Podcasts, Spotify, and other major podcast platforms. And to remind everybody, there is a video component which has some of the key figures and tables from the articles that we talk about. So this week, we've got another one of our patented six pack episodes where we are going to go over what is the coolest, most interesting new stuff in the literature from our perspective. Dr. Farris, why don't you start us off?

[B]

All right, Matt, I'm going to start with Merkel cell carcinoma. Everybody's favorite neuroendocrine skin tumor. I know.

[A]

So this was actually a good question for you, too. First of all, if you had to ballpark it, how many Merkels have you, like, actually seen in your real life in your clinic? Pat, and you first one, Ferris.

[B]

I have diagnosed two and probably, like, followed about five or six patients.

[C]

All right, so I, I, I follow a couple Merkels, but like, okay, so coming into the office, doing the biopsy.

[B]

Of North Carolina in my first six months here.

[A]

Okay.

[B]

And I actually, it was on my differential, so it made me look like I knew what I was doing.

[A]

Okay.

[C]

I always put it on my differential.

[A]

Yeah, I've never diagnosed one.

[C]

Yeah, I feel like versus Merkel, you never know.

[A]

Talk about a ton, but they're just pretty darn rare whenever you really look at it. But all right, fairs, go ahead.

[C]

Yeah.

[B]

Okay, so this is Gunnel et al. This was in JAMA Dermatology. And this is polyomavirus antibodies for Merkel cell carcinoma recurrence detection. So this is Paul Neem's group in Seattle. They are sort of like the gurus of Merkel cell carcinoma. And so they have really like, you know, specialty Merkel cell. That's all I think that Paul does, as far as I know. And they really have the largest Patient population. So they are kind of like my go to experts for Merkel cell carcinoma.

[C]

Okay.

[A]

All right. Some credibility.

[B]

Yep, credibility. So they ran what I think is probably the most, you know, comprehensive study on Merkel cell polyomavirus oncoprotein antibody titers for Merkel cell carcinoma surveillance. So do you know what those are, Matt?

[A]

I. I. I mean, I do now, but I didn't, like, four days ago.

[B]

Yesterday. Yeah. Okay. So basically, you know, we know that. Interestingly, overall, from the study, about 80% of patients with Merkel cell carcinoma harbor Merkel cell polyoma virus.

[A]

But how many? 80%.

[B]

You said about 80%.

[A]

Okay.

[B]

Actually do. Now, in this paper, 50% of patients had the antibody, but when they went back and looked at all of them, there was sort of this 30% group that was antibody negative. But when they, you know, looked at their tumor, they could actually identify virus in there. So that's why I'm giving you that, you know, 80% number. Okay. So Merkel cell polyomavirus, basically, you know, we all have mcv. Most of us that we bet, that's like, it's around. It's just, it only kind of integrates in and causes Merkel cell carcinoma in a subset of patients.

[A]

It turns out that you said we all have mcv.

[B]

Merkel cell polyomavirus. Yeah.

[A]

Okay. Sorry. Yeah, got it. Merkel cell virus. Okay. I was like, we all have a mean corpuscular volume.

[B]

We also have that, but that's.

[A]

Yeah. Okay. All right, go ahead. So we've also. We've all got the virus, but most of us don't.

[B]

So most of us have been exposed the virus, but it doesn't, you know, we don't have Merkel cell carcinoma. Okay. So. So anyway, what happens is that when you are. When you have the virus that integrates and causes the cancer, it exposes this NEO epitope and you make an antibody to that. So that antibody is a marker that says, yes, you have Merkel cell carcinoma that is virally driven. So this can be useful in following patients.

[A]

So they don't. So even though we, most of us have the virus, we don't have that antibody. Okay. All right, Good.

[B]

Okay. So 503 patients with stage one to three Merkel cell carcinoma were followed for a median of a little over four years. They had blood tests every three to six months measuring titers of this antibody. This antibody is called a Merck. It is a test, by the way. You can order it if you you know, search a Merck, you can order it at the University of Washington. So you can, you know, order the test, your patient can get it drawn and they can send it off. So anyway, what they found in the study, so, you know, they followed patients from diagnosis and then every three to six months. And so what they found was one, the higher your baseline AMERC titers, the higher your chance of recurrence. They also just sort of, they also found that if you are a zero.

[A]

That was not what I took from that graph.

[B]

So the, that was baseline. Baseline.

[A]

Yeah, yeah. So probability of recurrence free survival. If you were seropositive, you had a higher probability of recurrence free survival. And if you were seronegative, you had a lower probability. So it was good to have the antibody.

[B]

It's good to have the antibodies. But now we're talking for the people who are positive, what is your titer of antibody?

[A]

Oh, so the higher your titer, so you want to be positive and low tighter. That would be the ideal.

[B]

Yes. So in seropositive patients, so the people who have the antibody having a falling or negative. So, so having falling titer. So either a negative titer. So we're talking now when we do are doing surveillance throughout your course, having a falling titer or going to a negative titer predicts like over a 99 chance of being recurrence free for three months and like a 98.8% chance of being recurrence free at six months. So low titer is good. And then on the flip side, if you have a single rising titer, your risk of recurrence goes up to like 36% in three months or up to like 68% in two years. So, so you know, basically you following these titers, it can be really helpful because it lets you know, like, who do I need to worry about and who do I not need to worry about? And I think sort of the end game of this, if your titer is falling and you're, you go to, particularly if you go to a negative titer, you could potentially like avoid getting, you know, CT scans or PET CT scans. In that situation. The titer that the, the rising titer also was helpful because it flagged recurrence before clinical or like image based detection in over half the cases with a median lead time of about four months. So rising tigers were not always like immediate imminent recurrence, but they did suggest that you were at risk of recurrence. And then they did this, they looked at it sort of like on a per test basis and also on a per patient basis. So, you know, patients who had substantially higher risk of recurrence. So they had a substantially higher risk of recurrence after a rising titer versus with a following titer with it, like a hazard ratio of like 50:1. Okay. So, yeah. So Then the other thing that was kind of interesting is that the same group recently had an ASCO Abstract where they also looked at circulating tumor DNA and a Merck in the same patient. So two different biomarkers, CT DNA is circulating tumor DNA. Now, that's going to be, you know, you, you. That's not virally dependent. So Merkel cell carcinoma that is virus negative can also have, you know, will also shed tumor DNA. But that what they wanted to do is look in the patients where they could follow both. And so they had 171 patients, over 700 paired samples. In that group, they had 38 recurrences. So what they found was actually that a positive CTDNA was actually sort of a more ominous or worse prognostic factor than a positive AMERC test. So the hazard ratio for recurrence was over 27 with CTDNA versus 5.8 with, you know, rising AMERC. So CTDNA positivity was more strongly associated with recurrence. This is an abstract, so if you're going to ask me, like, every last graph, I can't tell you. All right?

[A]

You've already told me more than I wanted to know.

[B]

Okay. One year positive predictive value, 73% for CTDNA versus in that series, 51% for a Merck. So putting that all together, it is, if your patient has a falling or negative a mark titer. Very reassuring. You could probably, you know, you could probably space out their surveillance. Are we going to be the one necessarily doing this? Probably for the average derm, no. But I think it's nice to know. And I also think it's helpful. You know, why do I think that this is helpful? This is a test that we can order. And, you know, particularly if your oncologist wants to be. Wants to use this, which many of them probably do, you can at least send out, you know, order the Amarc test, send the patient. So when they go to see oncology, they have a baseline. And I think that, you know, time is kind of of the essence when we have these tumors. So, you know, I thought that that was sort of helpful. Um, you know, what kind of imaging. The author said that they generally do PET CT because it's more sensitive and that Is their that preferred imaging if it's available, CT scan if you can't get, you know, pet ct. So it's kind of the liquid surveillance era.

[A]

All right, so the quick summary. When you're diagnosed with the Merkel cell, it's good if you've got the antibodies because you got a higher overall survival there right at the beginning. But then once you've got the Merkel cell, you want your titers to be stable or falling. If your titers are rising, that's bad. And if you've got tumor DNA in your blood, that's bad.

[B]

You got it.

[A]

All right. Patton, you got anything you want to add?

[C]

No, but right. I mean I think on call, like for us we have a Merkel refer to he Monc, maybe think about checking that a mark. Although last patient we had with this, like we like that we couldn't do that. Like our send out lab, our send out lab was like, what are you talking about? And then, and so it was like six months before we figured out how to do it. And they do recommend that that a mark initial test be done within three months of the initial diagnosis. Because if you cut out Merkel, like if you're the one excising it, titers like drop pretty quickly from what I understand.

[B]

So like I think within, like I think this is about within a month of starting therapy.

[A]

Do they get, do they get MOHS or do they get wide local excision with a sentinel lymph node biopsy?

[B]

A ladder.

[C]

Everybody gets. Well. Yeah. NCCN guidelines, everyone gets sentinel node. Yeah, there are MOHS people that take out Merkel.

[A]

Okay.

[B]

Yes, the guidelines would say so I think that's actually a good take home point for, you know, the derm. Not practicing in a big multi center, you know, oncology or big, you know, oncology center. You don't just send these patients to mohs. They really need to go to surgical oncology. Everybody should get sentinel node biopsy. If you remember nothing else, remember that.

[A]

All right.

[C]

I think they could go see Mo, but I think it's part of a multidisciplinary like decision.

[B]

Yeah. I'm not saying mo's cannot be the removal, but you don't want to just say mo. You don't need to sort of enter the surgical oncology path.

[C]

Agree? Agree. Yeah.

[A]

Okay, let's move on. Pat and I can't wait for you to talk about this one. When you, when you put it in the thing and I was like, oh, but I know a study that shows that collagen does and then I was.

[C]

Like, son of a. Yeah, well, so that's the problem. Not that I have a huge interest in collagen supplementation, but this is the stuff. This is like the walking out the door questions where patients are like, what's your favorite sunscreen? Or what do you recommend for this? What do you recommend for that? And you know, hey, what do you think about collagen supplements? So I was reading in the Wall Street Journal a few weeks ago because you guys know I am sophisticated. And I saw the headline wonder pills are waste of money. The new supplements promising youth and beauty. And of course my first thought was like, it's a huge waste of money. Of course. But none of the healthcare providers interviewed said it's a huge waste of money for some reason. They interviewed two people who are co founders of the companies that make the supplements. Like, why would you do that? Yeah, there was one dermatologist at the end of the article who said if you only take the supplements for a short period of time, it is going to be a waste of money. So there. Shout derms on drugs. Shout out to Dr. Hallie McDonald. I think she practices in Austin. Wall Street Journal. That was not my six pack. But it was just a little clever lead in to introduce my first six pack which is titled Effects of Collagen supplementation on Skin Aging A Systematic Review and Meta analysis of Randomized Controlled trials by Myung and Park. And it was in the American Journal of Medicine September 2025. I just read the Wall Street Journal article when I came across my six pack article. So it could not have come at a more timely time. Why even do this study? There were already two meta analysis of randomized controlled trials that showed collagen supplements improve skin hydration and elasticity. We don't need to do anymore. We've prov. It works. This particular meta analysis sought to perform the meta analysis focusing in on study quality as well as funding sources for the individual trials. 893 records they got down to 23 included over a thousand patients. Conclusions. Collagen supplements work people. They actually work. They significantly improve skin hydration, elasticity and wrinkles. I think I'll introduce one of my own and retire a gazillionaire. Except I'm neither clever or hard working enough to found a company. So that's not going to happen. True. So now we can comfortably tell our patients to start taking collagen supplements, right?

[B]

No, because that study showed that it was only in the industry sponsored studies.

[C]

Exactly. So the authors went through. They went through and did some subgroup analyses, couple of interesting subgroup findings. Okay, so one subgroup, they looked at the source of the collagen. Fish collagen worked. Cattle or chicken collagen didn't. Pills and powders, not effective. You need to take collagen drinks. So like fish collagen soda. Like yeah, Mountain E. Disgusting.

[A]

Come on.

[B]

Like what is the worst beverage you could ever have?

[C]

Yeah, you vomit. You vomit a lot. Which helps with weight loss too.

[A]

So.

[C]

But the most interesting subgroup analysis looked at funding source and study quality. If the study was not funded by a far pharmaceutical company, it didn't demonstrate any benefits. If the study was a high quality study, it did not show any benefits. And they had these quality metrics that have been, you know, accepted as established measures of quality. So I am telling my patients that collagen supplements are very likely a waste of money. And with everyone on TikTok saying how much better their skin looks because of collagen supplements, I know mice, my advice will have no effect whatsoever. What do you guys think I'm still.

[A]

Going to be telling people to take? The one that I like is called Verisol V E R I S O L. It's not a brand, it's a, it's a, like that's an ingredient. Mainly because it is extremely cheap. So it's like six bucks a month. You get like a jar of the powder and it's like three months worth for like 30 bucks or something. It's like 10 bucks a month. And they have a in themselves funded trial that is randomized, double blind, super controlled. But it was funded by them. So now.

[C]

Yeah. So I have a couple of observations. Concerns. Number one, you, if an industry does the study and like I don't think they're making shit up. Like I think they're doing a randomized, double blind, placebo controlled study. Why is it that their studies work and if a non, like somebody just goes in and says I'm going to, I'm going to look at this study, I'm going to look at this supplement on my own and it wouldn't work. How are they doing this like consistently from this paper? How are they able to show that their stuff works?

[A]

No idea.

[B]

It could be sample size, right? You can afford to do a bigger study. You can also afford to pick multiple different endpoints if you're an industry study. It takes money to do these things.

[C]

So a few episodes ago with Dr. Tarbox we talked about the hair supplements and I went back to those studies. Every single one is, is, is comp. Is industry funded, you know so whatever the supplement was, if you looked at who funded the study, Viviscal neutrophil, the, even the pumpkin seed extract, like they're all industry. So is this probably true across all supplements that are not like drugs and don't have to go through the rigorous FDA sort of process? My sense is yeah, probably. What do you think?

[B]

I don't know. I still like my creatine. I think it works.

[A]

I believe creatine is different.

[C]

So creatine actually has a fair number of independent evidence. I did look at that because I'm, I'm a creatine person too. I started doing that.

[A]

What's it do for you?

[C]

Build muscle, increase decrease fat weight, increase muscle weight, blah blah blah.

[A]

Okay. Okay. Well I'm still, I'm, I'm still going to be believing industry sponsored trials for supplements. I, I, I'm still, it's, yeah, yeah.

[B]

I'm only recommending things that have a marketer behind them because they're the only ones that work.

[A]

No, but I'm going to recommend it by, by price. That is absolutely. My defining factor is, is yeah. If it's pretty. Right.

[C]

Because may maybe this helps. Very little downsides to taking a collagen supplement. I mean.

[A]

Yep.

[C]

You know they have like the radio tracer rat studies. I mean ingested collagen does make it into tissue, you know what I mean?

[A]

Yep.

[C]

But does it actually show any clinical benefit? We don't know. So if you're going to spend money, go go with the cheapest.

[A]

Okay. All right. We're gonna move on to my part of the six. First part of the six pack.

[B]

Your own personal six pack.

[A]

That's right. I get three. What are you talking about? My core again. Thanks Ferris.

[C]

It's hard not to.

[A]

So first I've got some topicals here. So first two that I don't really want to talk about but just put out there granulomanulare. Topical reflumelast worked. My main thing there would be that was a case report. I think oral reflumelast should be first line treatment for GA in general. But if you could get topical covered which you won't be able to. It worked. And then granulomatous rosacea case report of that responding to tapiniroff. So you know for both aryl hydrocarbon receptor vitama and PDE4 receptors or Eve. Great. Some kind of pain in the butt things that they work for but doesn't really matter. You're not gonna be able to get em covered. Now let's get on to what's actually interesting here. So ruxolitinib and believe it or not, I was first author on this. So self promoting on the podcast part of Docs Dermatology, D O C S Dermatology.

[C]

I want how much of the article did you actually physically write done.

[A]

But I, but I, I put together an outline. So we had a phone call and I made an, we did a detailed outline that was kind of the draft and then when they, you know, then they put it together and then I like like very carefully read it, made tons of changes and recommendations and the whatever. So I, I did a lot. I like all right. It was, I believe. Yeah, it wasn't like they wrote it and I like signed off on it like it was a lot of work. So the main takeaway here. So this was efficacy and safety of ruxolinib cream for the treatment of moderate to severe chronic hand eczema. Results from a 16 week multicenter randomized double blind study. So this was ruxolitinib versus placebo. Good old Opzelura. And their IGA success rate was 53%. So we can say most people. So the big thing about this study though, they excluded anybody with atopic derm. So it was supposed to be primarily, you know, hand eczema of unknown etiology. So probably a mix of ad, sorry of allergic contact, irritant contact and endogenous. But if you had atopic dermot, it was a pre existing diagnosis, you couldn't be in the study. So they, they right now.

[C]

So. Right. My big thing is chronic hand eczema is atopic term like it always has been. So like that.

[A]

I would, I would argue that chronic hand eczema is always irritant contact dermatitis with either superimposed eight with it's either ICD plus AD or ICD plus ACD or all three. But I, because right. If somebody came in and said with AD and you said well tell me about your bathing and they said I get six showers a day, you would say well you've got some irritant dermatitis. Let's see if you know, maybe that's what's going on here. And since we wash our hands six times a day, I think they all have some irritant derm. So. Right. And this gets it. You're getting into the problem with hand eczema is like should, if it's not ICD or acd, should we just call it ad? And I, I kind of agree that's a yes. But in A lot of the pharma stuff they talk about, they, they're only going to call it AD if they have AD affecting other areas. All right, so.

[B]

And I think AD is not all one disease, by the way. The young people who got it and they've got asthma. It's a different group than the old itchy people, but all ad, but different flavors of it.

[C]

So I, I guess if somebody came in with chronic hand eczema and they never had atopoderm anywhere else, it's like, all right, you, you're washing. I'd say they're a cook, right?

[A]

Yes.

[C]

Where you can see chronic hand eczema. You're, you're working with food, you're washing your hands. I know none of the other cooks have chronic hand eczema. So why do you have it? Because you probably epigenetic change and like to keep it simple. Like an epigenetic change in flagrin in their hand. Like so. Etiologically. Etiologically. It's, it's atopic derm. It happens to be localized to your hands. Yeah, I, I don't, I'm so baffled by this chronic hand eczema and they're like the first and only treat like there. I have a lot of things that I can use to treat chronic hand eczema that are FDA approved to treat chronic hand eczema because it's atopic derm.

[A]

I would argue that it is always, it's always an overlap of multiple types of dermatitis. It's either pure ICD or it's AD plus ICD or ICD plus acd.

[B]

We're talking irritant contact dermatitis, allergic contact dermatitis.

[A]

And the reason that matter soup here. And the reason that matters so much.

[B]

Is matters more to you than anybody else.

[A]

Very, it's very clinically relevant. So topical steroids make irritant contact arm worse. So they relieve the symptoms, but they make your barrier function worse. So you stop making lamellar bodies and you stop making intercellular lipids. So whilst clobazole will make your contact arm feel better, it makes the underlying disease worse. And the key thing with Opzelura and Zupco, the new Delgacitinib is specifically approved for chronic hand eczema is that they don't have that adverse effect on the barrier. So you're much more likely to actually get people better with these than with clobazole. Now, we don't have head to heads to prove that, but if clobazole worked great for hand eczema they wouldn't have been so excited to try and be pursuing this. But back to the study here. So rucks IGA success rate of 53% versus 11% for placebo. So most people got to clear. Almost clear. Now the big question, right? And so Ruck's HEXI 75 Hand Eczema Severity Index, 80% of people got 75% better versus 27% with placebo. How does that compare to in Zipco and Zip Go had an IGA success rate of only 25%. But there's a very good reason for all of this that I'm going to get to. So it only added a Hexi 75 rate of 50%. So by sheer numbers just looks like it's not as good as Opzelura. But number one, the two trials use different IGA scales. So clear, almost clear for the Opzelura trial could have redness and or scaling. So very minimal, barely visible scaling. For the end Zupco trial, you could only have barely perceptible erythema. If there was one flake, you were mild. So that is a big difference. Number two, the Delgo trial was done only in Europe. The absolute trial was done in Europe and the US and this was one of the first hand eczema trials in the US So none of us knew how to do the Hexi scores very well. And then finally, the Rux trial excluded a people with pre existing known atopic derm and Delgo didn't. And the people with known atopic derm were some of the worst responders to the Delgo, to the Adzubgo. So to some extent in the Rex trial they almost weeded out some of the hardest patients. So this is really a case where I don't, although by sheer numbers I would say it just looks like Abzelura was bad. You truly cannot. This, this is a situation where we're looking at different diseases, different endpoints, very different trial populations and investigators. You really can't look at this and say that, that Opsolur is better than in Zupgo. You can just say both because they both work for hand eczema. It probably ought to be like which one is easier to get is probably what should be driving which one we prescribe.

[B]

And does the patient have atopic dermatitis too? If they have atopic dermatitis too, you should use Opzelura. Would you say that?

[A]

I would say that. I think that whether they have, I mean, if they have atopic dermatitis as well, I guess you give them Opzelura and then. But in like a practical sense, I think they're pretty much identical drugs with the exception that the Nzupco doesn't have any propylene glycol in its vehicle. So that, so it. Yeah.

[C]

Do you anticipate ruxolitinib pursuing a che indication?

[A]

I don't think so.

[C]

I, I don't, I just, it wouldn't make any sense.

[A]

Yeah, I don't. It'd be like, I've always told that company, like, just like if I'm comfortable saying that if you got hand eczema, there's a component of AD to it. Unless it's pure allergic contact derm, where, okay, try, you know, changing to a fragrance, try, you know, using only CeraVe hydrating cleanser. And if your hands get better than fine or change your gloves. But if, if, you know, treating it as allergic contact term doesn't get them better, then I'm comfortable calling it AD already. So why, why spend hundreds of millions to get another indication?

[C]

It's, we, it's, it's kind of going to pose a weird situation which I don't anticipate will actually be this clinically difficult. But say you really want Anzipco. You've seen the data. You're like, yes, this is perfect. Chronic hand eczema. There's this FDA approved drug, you're, you have chronic hand eczema and the Delgo, it doesn't get them any better. And then you're like, I want to actually give you systemic medication. Your hand eczema is so horrible. I think doopie's really, really going to work. Well, we're just gonna have to change your diagnosis to atopic derm. Whereas like from the get go, it would be just like, this is atopic derm, there's a hand eczema predominant or maybe exclusive component to it.

[A]

It's just weird. I think what, I think what's going to happen is that that initial diagnosis, you would call it dermatitis unspecified, treat them with ansupgo. And then when they didn't get better, you would say, okay, it's not unspecified anymore. Now I think it's atopic, but you.

[C]

Don'T get these letters. Like, there is no diagnosis of chronic hand eczema in the chart. Like I get those. I mean, not, not specifically che, but intrinsic atopic dermatitis. You just called it atopic dermatitis. Or, you know, it's, maybe it's just the, it's the, the insurance environment in western Pennsylvania.

[A]

If you're Going for an AD drug, you got to say it's AD of the hands, which I think is true in most cases, like generally true. There's no way to prove it's not. And if it's.

[C]

Yeah.

[A]

If you're going, I think you call it dermatitis unspecified of the hands.

[C]

But probably both like really good drugs, right?

[A]

Yes. I don't will never have a head to head, but I, my guess would be that they're going to work the same.

[C]

Okay.

[A]

In theory, it is important that it looks now like they both seem to touch tick 2 because tick 2 seems to be more important for irritant hand dermatitis than does JAK1 and JAK2. So just interesting thing. All right, let's, let's move on to our next article here. Dr. Farris, what do you got next?

[B]

So I went from the most serious to the least serious. So I have efficacy, safety and recurrence in seborrheic dermatitis. A dose dependent analysis of oral isotretinoin 10 milligrams versus 20 milligrams. This was, this paper was in. I didn't write it down. Was this in jad?

[C]

It's jad.

[B]

It's in jad. So I picked it because it was like an investigator initiated study. A drug that we use a lot of something we all see every day. And because it was done in Turkey and because the first author and the last author have the same last name. Demir boss.

[C]

Okay, that's a good derm name.

[B]

It is. It is like the boss of Derm. All right, so what they did was this was a retrospective study of 234 patients who were treated with oral isotretinoin 10 milligrams a day versus 20 milligrams a day. So kind of half and half, 100 a little more with the 10 milligrams a day for a minimum of three months. But an average of 4.2 months in the 20 milligram and 4.5 in the 10. Women, interestingly, were more likely to be on the high dose. And patients who'd had Seb derm longer were more likely to get 20 milligrams. Why did they pick to treat seb derm with isotretinoin? The oil thing would make sense. Why 10 or 20 milligrams? I have no idea, but they did. So what did they find? What do you think works better? Higher dose, 20 milligrams, better disease control, DLQI, patient satisfaction, all better. With 20 milligrams, the probability of being recurrence free. So we get to talk about recurrence free survival across both of my papers, but very different contexts. At one month was 83% on 20 and 42% on 10. And at a year, it was 36% from the 20 group and 14% in the 10 milligram group. So, you know, adverse events. Amazingly, they said there was actually more like myalgias and epistaxis in the 20 milligram group. I feel like that's. But interestingly, the 10 milligram group had more dry lips and skin. I feel like that's all kind of.

[C]

I don't know, like, nosebleeds. For the 20 milligram, it was 40.7%. That, that's. That's an insanely high number. For 20 milligrams of isotretinoin, they had.

[B]

To have been intentionally eliciting it. Like, it probably wasn't like, er, you know, nosebleeds.

[C]

Yeah. I just like when patients on acne doses of Accutane are complaining about dry lips and my nose is dry and this, I'm like, all right, we're gonna go down to 10. You're not gonna have any of those side effects and you're just gonna have to take it for a year. And you're right, maybe I'm not eliciting those. Well, how many. Is your dryness better or what? It's just right. Those numbers were surprising to me. What are they doing over there in Turkey?

[B]

Yeah, I don't know. I don't think I've ever done like 10 milligrams a day of isotretinone for anything. But. So, you know, there's probably a lot of selection.

[C]

Some acne patients are like, just can't. Everything's dry. Yeah.

[A]

So, but my, my. So the all right, takeaway was. Seems to work while you're on it.

[B]

Yeah, it sort of works while you're on it. If you're gonna do it, go big or go home and, you know, slightly no waste with no weight based dosing here.

[A]

Yes.

[B]

So, you know, what's your Anatolian average size? I don't really know. Just wanted to throw out that adjective.

[C]

So, yeah, I got Anatolians all the time.

[B]

I know.

[A]

For those of our listeners who, by context, I'm believing Anatolian means Turkish.

[B]

Yeah.

[A]

So the one thing this reminded me to throw out there is don't forget that, uh, for somebody who's got sebaceous hyperplasia, isotretinone is actually a very effective therapy. So there's some data out there. 40 milligrams a day for two months really shrinks them down. And, and they probably eventually do. I mean whenever I've used it they do eventually come back, but it can be like five years before they come back. The sebaceous hyperplasia, I think it's better for that than for September.

[B]

Agree. I agree. That is good. I've had that with like renal transplant patients who have been on like TUS and gotten lots of sebaceous hyperplasia. So yes, that's the take home message. It had nothing to do with the paper. All right, done.

[A]

Next study. Patton, what do you got?

[C]

It is from August 2025 issue of Biomedicines. I don't think I've ever read anything from Biomedicines. So excited. Actinic Chelitis A systematic review and meta analysis of interventions, treatment outcomes and adverse events by Al Fartsi et al. Some general background information on actinic cheilitis just for you know, general info. It is considered a precursor to SCC of the lip. I don't know why I wrote that down. Progression rates of 3.2 to 16.9 to invasive SEC. So AKs probably over treat. I'm not worried about most AKs. We could probably leave them alone without any significant consequence. This is in of course the non transplant patient Actiniculitis kind of worries me when patients come in and they have like the scaling and the cracking and this doesn't heal and you look at them and you're like this is probably a actinic cheilitis that I think probably deserves to be addressed More so than just run of the mill cutaneous AKS. Lip SCCs have a have a higher metastatic potential compared to cutaneous secs. So they went through this 2000 records after screening exclusions they included 36 studies in the final.

[A]

Blah blah, blah. Get to the point.

[C]

Efficacy was determined by clearance rates and recurrence rates. I was like meta analysized out at this point. I don't understand anything from meta analysis. They talked about generalized linear mixed model.

[A]

What works?

[B]

Talk about that on what works and.

[A]

What doesn't work and. Right. So assume that the thing is clearance is what's the likelihood it's going to get rid of it and then recurrence. What's the likelihood it's going to keep it from coming back. Right, right.

[C]

Two forest plots that pretty much lay it all out. CO2 laser and Michel mod had the highest clearance rates. Figure 34 is plot for recurrence rates and once again, CO2 and a Miyomod come out on top. So I guess those are the top two most effective options. This wasn't anything that was surprising, but I hadn't read anything on actiniculitis in a while. And so it was kind of n to sort of reassure what I always thought. The problem is that most derms don't have a CO2 laser on hand, and so there'd have to be a referral. And one time I actually referred a patient with biopsy proven actiniculitis to get CO2 laser because I knew this other office had it. And they sent the patient back saying, this isn't actiniculitis. So that was a little frustrating. And the problem with that, they had.

[B]

Isotretinoin and it was just a dry wet.

[C]

It was the weirdest thing. I, I didn't know what to, to say to the. I'm like, I feel really bad. I mean, it was biopsy proven. We sent them the path, whatever.

[B]

Maybe it doesn't all I could take.

[C]

Maybe it doesn't get reimbursed and the patient didn't want to pay out of pocket. I don't know, maybe I missed something.

[A]

All right, so the takeaway would be ideal treatment according to this then is imiquimod. More so than 5 fu or other stuff that is accessible to us.

[C]

So 5 fu didn't even have a study. So it wasn't included. There was, I think there was a study in the recurrence, but there wasn't an efficacy. And the problem with a MI mod is like, I would never use a Michel mod. If you use field therapy on the lip, it is an absolute disaster. Those patients, like wind up in the ER with swollen, cracked, painful, can't eat lips. So I don't know what to do.

[A]

What if you just. So what I would do is unless they give a regimen here, I would have, I would be like, okay, try putting it on just once a week for a couple weeks. If it doesn't, it's not a disaster. Then try going like Monday, Thursday.

[C]

And if it's not, that's probably the way to go. It was interesting. So it was two studies that looked at the efficacy. So I went and looked up the studies. One of them, they did it daily for eight weeks. The other used it three times a week for four to six weeks. And both papers said when it got too bad, they told the patients to stop. And conclusions from both of the authors that did those two separate studies were like, we need A different regimen. These reactions are absolutely terrible, but they just kind of left it open. So I think you're right, Matt. I think like if you're going to use topical, it is just going to be the wimpiest sort of regimen that.

[A]

You would ever do. Right. Like once.

[C]

What I actually did ever. Yeah. What I actually did with that patient is I did cryotherapy. That was not part of the analysis, but we have that. That's easy to do. You can actually freeze the whole bottom lip. I actually did it in like thirds. The patient tolerated it well, as well as you tolerate any AK freezing. And it worked. She came back, the cracking was gone. It finally healed. She was very happy.

[A]

Why'd you do it in third? So that you could charge three visits, you know.

[C]

Absolutely. That's why I did it. Yeah.

[A]

No prescribed.

[C]

I prescribed a medication as well, like.

[A]

Tac so you could get a recovery level four.

[C]

I could get it up to a 214.

[A]

So. But you did it. You did a third of a lip at a time so that she could still eat through the other side. Sue. Whichever part. Yeah.

[C]

I thought it was a tolerance issue. I was patience first man with me. It's not funny.

[A]

The other thing that would be interesting here, of course we've talked about how we think. How the data seems to suggest that 5fu calcipatrine combination is highly effective in as long term efficacy. That that'd be another option to think of to use as a like. Okay. Try it a couple times a week to start. Blah, blah, blah.

[B]

That is what I do.

[A]

Okay. Do you do it, do you do it with like specifically?

[B]

Yeah, I have done. Yes, I will do it for actinic cheilitis. It. Everything's brutal with actinic cheilitis.

[A]

Do you have them taper up with it or do you, what do you do?

[B]

I just say do it. I, I tell them they can do it for like five days. And I'm like, if it just becomes too bad, just stop.

[A]

So five days and then you're done or five days on then I'll say.

[B]

Five days and then you're done and then cut. But I'll bring it back in a few months.

[A]

So why not do like five days a month? Like five days. Like do it for five days. Then next month do it for five more the next month do it for five more, then come back.

[B]

I, I feel like you got to just sort of see these people, do something, tell them do it. You're going to, it's going to be really bad. When it gets bad, stop and then let it heal and then come back and let me see. I feel like it's so tailored and individual with actiniculi.

[A]

Okay, okay.

[C]

Not that I want listeners to know, like, how bad my skin is, but I, I did that combo on a little AK above my eye, like, for five days. I was a mess for like two weeks. I mean, people coming in are like, oh, my gosh, what happened to you, huh?

[B]

Relax.

[C]

Okay. Yeah, maybe I'm just a sensitive person.

[A]

We know you're sensitive, Dr. Patton.

[C]

Thank you.

[A]

We know. All right, let's move on to my second batch here. I've got one main one that I want to get to, then a couple quickies, some more miquimod. So this was just a study of radiation versus imiquimod for difficult Lenigo maligna. Main takeaway was that imiquimod, 5% Monday through Friday for 12 weeks, tailored to putting on enough so that they got erythema without pain. So increasing or decreasing 92% success rate in treating Lenigo maligna. So really an interesting. Now two thirds required an adjustment of frequency or, you know, they didn't get erythema with five days a week, so they had to go at a retinoid or occlusion, but tailored it to where they got some, some irritation, but not, not where they had, you know, however, frequently you had to. So up to five days a week. So big question here. So the letting go, malignant, not letting go. Right. So I wasn't exactly sure if these were invasive or not. I don't think that I, I think they did invasive or non invasive. Do you guys offer this for Lenigo maligna or do you tell people to go get Moe's or what do you like? To me, this probably ought to be our first line treatment for Leno maligna. It's.

[B]

It's a discussion. I think each lentic, each Lentigo maligna is like its own discussion. Because if it's small enough and it can get mosed off, that's generally going to be the answer if the patient is super old.

[A]

If you have a surgeon who does it.

[B]

Yes. This is why everyone should stay in academia, because then you always have that. Yeah, no, I. But it is, I think it's just, it's just a discussion. Right. And like, there are 99 year olds who, like, we should maybe do nothing with, like, it's so individualized. I have a hard time saying, this is my protocol for lenticomaligna.

[A]

Patton, what do you Do?

[C]

Yeah. If it's a Lentigo malignant in a patient who will tolerate surgery, then I biopsy it and I send them to surgery. And if it's a Lentigo malignant in a patient where you're like, man, they would not tolerate surgery, a lot of times it's because that patient just is not in great shape. And, and I. So you don't even biopsy it. You just kind of say, this probably is lentigo malignant, and it's not unreasonable to just kind of watch it and make sure it doesn't become anything more. But I suppose if I did the biopsy and it came back with the diagnosis, I. Right. I. Like Farah said, you have the discussion. We don't need to do anything because these are not aggressive and we can follow it. If the patient's not going to tolerate surgery, you have these two options. The, the problem with both of those options is radiotherapy is not great because they have to go in for like, what was the average, 30 treatments. Right. So I could see the family saying, we're not going to do that. And then applying a Michael Mod little packets and putting it on twice a day.

[A]

Once a day.

[C]

Once a day for 12 weeks. They're. They're not going to do. You know, I. Is. Is the compliance going to be good there? It's. It's like, there's not a lot of great options. And so you have the discussions. And if the patients are like, I want to do the easiest thing, for me, it'd probably be a Michel Mod, and we could at least tell them that, hey, numbers are good. Do I expect them to be compliant with this particular protocol? Not really.

[A]

Okay. All right. All right, let's go. My other two quickies. So premolast in the treatment of central centrifugal cicatricial alopecia. An open label pilot study. So it's 20 patients, 15 patients finished it. Most of the endpoints were somewhat better at 24 weeks. It wasn't like, woo, but. Right.

[C]

I did. I said that when I read this.

[B]

What is like, serious? I think like prednisone or something or. Yeah.

[A]

So it at least gives us, you know, it suggests to me that oral reflumelast would work. Well, since we know oral reflumelast works better than a premolast, or at least we strongly think that. And it's cheap. Right. We said try. I try and get in some oral flumelas plugs every episode. $6 a month on Mark Cuban's Cost plus pharmacy. Last time I checked and works just as well as the premolast. Listen to some of our prior episodes.

[B]

About dosing on that. Like what's. What's his show. The. The. What's the show? The Sharks are all. Maybe you could suggest starting a oral reflumelast company and he would invest in it because everybody would buy through it. You could market. You could have a Speaker's Bureau. I think you. I. I think I see where you're going with this.

[A]

Yeah, I'm working on it.

[C]

Cyrus, you seem a little unstable, and for that reason, I'm out.

[A]

All right. And then my. My last one. This was actually in the Journal of Investigative Dermatology, so. Big time journal. This was actually a commentary about the real article. Drugs and bugs in atopic dermatitis. Benefits to the skin microbiome from targeted immunotherapies maintained they. They did four different arms. JAK inhibitor, one arm, Doopy, another arm, Sex sport, another arm, and topical steroids another arm. And basically what they showed was that Doopie and Jax improved the skin microbiome in addition to improving the disease, whereas cyclosporine did not improve the skin microbiome. Because it's been an interesting question of. Now, Doopie improved it more than the jaks. And that makes sense because IL13, whenever it signals it, reduces antimicrobial peptide production. That's why you get covered with staph and so Dupy, since it blocks IL13 more densely than Jaks, it improved the microbiome more, meaning it got rid of more staph than did Jaks. But what this really showed to me, since cyclosporine didn't do that, was that getting rid of the staph isn't just because the disease got better. The drug does matter. And if so, if you've got somebody who's got AD and getting a lot of infections, probably IL13 inhibition. We don't have any evidence that one of the drugs, you know, Doopie versus Adbri versus Eb Glis. We don't have any evidence that one of them is better at getting rid of STAPH than the other. But I've seen more data for Dupy and Trelo or. Sorry, DUPY and Adbri than I have for Lebri or ebglis. Sorry. But I imagine all three of them equally benefit your microbiome since we know that IL13 inhibition helps to get rid of staph. That's the main. That's the takeaway. The other thing that was interesting here, before I forget, I learned what quorum Sensing means I've been reading that in a lot of gut microbiome studies. So quorum sensing is that once a particular species of bacteria gets dense enough, gets enough population density, then they can detect each other, realize, hey, we've got enough of us here that we can do something. And then they start to secrete proteases or toxins or form a biofilm or whatever. And so just an interesting thing that if you've got a little bit of staff, it may behave completely differently than if you've got a lot, because once you get a lot, it then senses quorum and starts to make these proteases and toxins that damage your epidermis directly as a protease and drive inflammation as a toxin. So that was interesting, too.

[B]

It's like that scene in Gladiator where they're like, together we can survive. And they all get together and then they fight off the things that come at them.

[A]

That's right. All those chariots and whatever.

[B]

Yeah.

[A]

How many times a day do you think of ancient Rome, Patton?

[C]

A lot. Like, every day. I, I. There's a History of Rome podcast. It's got like 270 total episodes, and I listened to the whole thing, and then I started it over again and started listening again. So quite, quite nice. More than anyone that I know well wants me to.

[A]

Okay. What. When do you listen to them?

[C]

Running, exercising?

[A]

Oh, right now, actually.

[C]

It's way better than our podcast. If you're listening cars, I advise you to switch over to that one.

[A]

And I would, I, and I want to let everybody know that when I listen to our episodes, I listen to them on, like, 2x. I can't. Oh, my gosh. Do you listen to either of you listen to any podcasts at regular speed, or do you always speed them up?

[C]

I'm a 1.25x his history Rome I listened to.

[A]

Okay, yeah, 0.75.

[B]

So it goes on longer.

[A]

All right.

[C]

Oh, well, you know, what I was going to say is that the microbiome thing, it actually reminded me of, like, the hand eczema with the jacks. Right. It's like there's more to it than just calming down the inflammation. Right. And steroids hurt the, the barrier. And that's why, like, it can be okay, but why Jacks may be way better. And it's just a difference of cyclosporine and doopie. You have good responses to cyclosporine, right? You've had these atop patients, even cyclosporine, and they're like, okay, yeah, I'm better, but it's not the. This has totally changed my life that you get with Doopie and I. I wonder if it's because it's. It's addressing more than just the inflammation. It is addressing microbiome and you know what I mean.

[A]

In the itch sensitization, right? So the IL13, that is IL4 and IL13 that are expressed on itch neurons. So you're calming down the itch neurons. You're fixing the microbiome, whereas cyclosporine is kind of doing those things, but it's only doing them by removing the inflammation. It's not actively improving antimicrobial peptide production or reducing the hypersensitivity of the itch neurons. That's interesting. All right, well, we are going to wrap it up there. So I want to thank everybody for joining us this week. If you got, you know, questions, comments, ideas, you can shoot us an [e-mail] I hope you learned a few things. I hope you laughed once or twice. But mostly I'm hoping you're planning to join us next week. Until then, I'm Matt Zyrus.

[C]

I'm Tim Patton.

[B]

And I'm Laura Faris. And we are derms on drug.