Are You Serious? Tattoos Prevent Melanoma and More Curiosities from the Literature

Summary

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Episode Summary: "Are You Serious? Tattoos Prevent Melanoma and More Curiosities from the Literature"

Podcast: Derms on Drugs
Hosts: Dr. Matt Zirwas (A), Dr. Laura Ferris (B), Dr. Tim Patton (C)
Date: October 31, 2025

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Episode Overview

In this "six-pack" episode, the Derms on Drugs trio each present and dissect two recent articles or curiosities from the dermatology literature. The theme: surprising findings, practical pearls, and controversial headlines—like whether tattoos might actually lower melanoma risk. The hosts maintain their trademark mix of clinical expertise and comedic banter while giving practical advice for dermatology providers. Each segment includes discussion of real-world implications, study methodology, and take-home messages.

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Highlights & Key Discussion Points

1. Switching JAK Inhibitors in Alopecia Areata

[01:14–09:31 | Laura Ferris]

• Study Brief: Yale case series (Khalil et al, JAMA Derm): 13 patients with severe alopecia areata who failed at least one JAK inhibitor, then responded to another.
• Key Finding: Some patients had dramatic responses after switching, even after multiple prior JAKs.
  • “One person actually went through four rounds. They went to four JAK inhibitors before they had hair regrowth.” – Laura Ferris [05:20]
• Clinical Nuances:
  • Not all JAKs are interchangeable; different subtypes may matter.
  • Real-world cases included adjunct therapies (oral minoxidil, intralesional steroids).
  • Weaknesses: small sample, retrospective, variable protocols.
• Pearl: Give at least 9 months on initial JAK and consider adjuncts before switching; oral minoxidil is safe and should be considered early.
  • “I think you add the oral minoxidil early and continue it on.” – Laura Ferris [07:52]
• Philosophy: Some prefer monotherapy, others combination—no consensus among the hosts.

2. Intralesional Therapies for Keloids & Hypertrophic Scars

[09:36–15:58 | Tim Patton]

• Meta-Analysis (Li et al): 24 RCTs comparing IL (only) therapies.
  • IL Botox and triamcinolone + 5-FU (TAC+5FU) performed best for efficacy and recurrence over triamcinolone alone.
  • Odds ratios: ~5 for Botox, ~4 for TAC+5FU.
• Practical Barriers: Logistics of compounding/administering 5FU are significant.
  • “There are a lot of logistics to it and I think a fair number of providers are like, I’m not dealing with any of that…” – Tim Patton [11:40]
• Protocols: Most use TAC (various strengths) and sometimes cryo; electron beam radiation for recurrent cases, but coverage varies.
• Memorable Moment: Banter about the “satellite dish” filter for drawing up 5FU and intra-institutional differences in practice.

3. Tattooing and Risk of Melanoma

[16:07–19:12 | Matt Zirwas]

• Utah Case-Control Study: Individuals with ≥4 tattoos had >50% lower melanoma risk; those with ≥3 large tattoos had 75% lower risk.
  • “Maybe you're priming people's immune system so that when they get a melanoma they already have some reactivity.” – Matt Zirwas [17:36]
• Host Skepticism:
  • Laura Ferris: “I’m glad it’s a video podcast so people can see me rolling my eyes...” [17:53]
  • Patton notes age confounding; Ferris posits detection bias (tattoos hide lesions).
• Takeaway: While fun to discuss and possibly a party fact, hosts don't change clinical practice based on this.

4. Tinted vs. Untinted Sunscreen for Melasma

[19:12–22:43 | Matt Zirwas with group discussion]

• Study: Randomized trial, tinted sunscreen (with iron oxide) vs. untinted, in melasma patients—the tinted group improved markedly over summer while the untinted group did not.
  • “The people who got the tinted sunscreen, their melasma got a heck of a lot better over the course of the summer, like impressively better as monotherapy.” – Matt Zirwas [20:40]
• Mechanism: Visible light appears to be a major trigger for melasma, especially in darker skin types.
• Practice Pearl: Strongly recommend tinted sunscreen, particularly in phototype III/IV.
• Open Question: Less clear if effect translates to very light-skinned individuals with melasma.

5. Dupilumab Exposure During Pregnancy

[23:11–32:23 | Laura Ferris with group discussion]

• Cohort Study (JAD): ~293 dupilumab-exposed pregnancies vs. matched controls—no elevated maternal risks; possible reduced risk in some adverse outcomes for women with type 2 inflammation.
  • “There was actually a reduction in… preterm labor… hazard ratio 0.11, which is pretty significant.” – Laura Ferris [28:38]
• Limitations: Could not assess neonatal/child outcomes, only maternal; timing/duration on drug varied.
• Practice Implication: Reasonable to continue dupilumab when trying to conceive; consider pausing during pregnancy unless significant disease flare.
  • “What I would probably do is hold your dupixent and then if your eczema starts to come back... restart.” – Matt Zirwas [30:08]
• Broader Point: Risks of stopping therapy (uncontrolled disease) also matter; treat type 2 inflammation during pregnancy.

6. Kappa Opioid Receptor Agonists for Uremic Pruritus

[32:27–38:04 | Tim Patton]

• BMJ Study: IV kappa agonist (Anarikafon)—primary and secondary endpoints met for pruritus reduction in dialysis patients; side effects similar to placebo except for dizziness.
  • “37%…reached the primary endpoint…compared to 15% in placebo.” – Tim Patton [34:30]
• Clinical Context: Most use now falls to nephrology; dermatologists see fewer cases due to new renal treatments.
• Bonus: Butorphanol (intranasal, Kappa agonist/Mu antagonist) historically effective but hard to prescribe now.

7. Oral JAK Inhibitors for Vitiligo

[38:07–42:59 | Matt Zirwas with group]

• Retrospective review: JAK inhibitors show modest efficacy for vitiligo; most patients also on UVB/topicals. Results improve with longer duration (but drop-off and observer bias likely).
  • “About half…got 25% repigmentation only 10% got 75% repigmentation…” – Matt Zirwas [39:28]
• Key Insight: JAKs less transformative than expected; uncertainty about durability (does repigmentation persist after stopping?).
  • “You took a patient that had vitiligo and turned them into a patient that has vitiligo. It’s better…but…” – Tim Patton [41:57]

8. Topical Timolol for Chronic Wounds and Hand Eczema Fissures

[42:59–45:52 | Matt Zirwas, group]

• Case Report & Theoretical Discussion: Cheap, accessible topical timolol (ophthalmic solution) appears helpful for chronic wounds and recalcitrant fissures.
  • “Topical Timolol is cheap, easy to get, and you just put a drop on the fissure…” – Matt Zirwas [43:50]
• Mechanism: Beta-adrenergic effects on keratinocytes.
• Caveat: Rare risk of allergic contact dermatitis.

9. Mendelian Randomization Studies—Skepticism

[45:56–46:49 | Matt Zirwas]

• Hosts note the mass retraction of Mendelian randomization studies; agree these are rarely conclusive for clinical practice and best regarded with skepticism.

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Notable Quotes

• “Switching jacks can help no matter how many jacks.” — Matt Zirwas [09:31]
• “Maybe you're priming people's immune system so that when they get a melanoma they already have some reactivity.” — Matt Zirwas [17:36]
• “There is pretty overwhelming evidence… that visible light is a big factor in melasma.” — Matt Zirwas [22:08]
• “There was actually a reduction…in preterm labor…if you had type 2 inflammatory disorders and you were on dupilumab…” — Laura Ferris [28:38]
• “You took a patient that had vitiligo and turned them into a patient that has vitiligo. It’s better…but…” — Tim Patton [41:57]
• “Topical Timolol is cheap, easy to get, and you just put a drop on the fissure…” — Matt Zirwas [43:50]
• “Maybe I’ll tell my patients to take nicotinamide and get three huge tattoos.” — Tim Patton [19:07]

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Timestamps for Major Segments

| Segment | Host(s) | Timestamp | |---------------------------------------------------|------------------------|-------------| | Switching JAK inhibitors in alopecia areata | Laura, Matt, Tim | 01:14–09:31 | | Intralesional keloid therapies | Tim, Laura, Matt | 09:36–15:58 | | Tattoos and melanoma risk | Matt, Laura, Tim | 16:07–19:12 | | Tinted vs. untinted sunscreen for melasma | Matt, Laura, Tim | 19:12–22:43 | | Dupilumab in pregnancy | Laura, Matt, Tim | 23:11–32:23 | | Kappa agonists for uremic pruritus | Tim, Matt, Laura | 32:27–38:04 | | Oral JAKs for vitiligo | Matt, Laura, Tim | 38:07–42:59 | | Topical timolol for chronic wounds/fissures | Matt, Laura, Tim | 42:59–45:52 | | Mendelian randomization skepticism | Matt | 45:56–46:49 |

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In the Hosts' Own Words (Memorable Banter)

• Laura Ferris [17:53]: “I’m glad it’s a video podcast so people can see me rolling my eyes and Patton smirking at this study.”
• Tim Patton [19:07]: “I know I’m gonna tell my patients to take nicotinamide and get three huge tattoos.”
• Matt Zirwas [22:08]: “Come on, Pat. There’s not some evidence. There is pretty overwhelming evidence to me at this point that visible light is a big factor in melasma.”

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Practical Pearls

• For severe alopecia areata, be patient with JAK inhibitors and consider adjuncts—switching is reasonable if no/poor response after 9+ months.
• For keloids, consider TAC+5FU for better efficacy/recurrence, but administrative logistics may limit use.
• Melasma patients (esp. Fitzpatrick III/IV): Tinted sunscreen is likely superior to untinted—make it your go-to recommendation.
• Pregnancy and dupilumab: No signal of increased maternal risk; balance disease control and fetal exposure—stop if possible but restart for flare.
• Severe uremic pruritus: If renal team has not tried a kappa agonist, suggest they consider it; butorphanol is rarely used now due to script restrictions.
• Vitiligo: Oral JAKs may take many months and results are less robust than biologic use in psoriasis—set expectations.

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Useful for Listeners Who Haven't Tuned In

If you missed this installment, you missed spirited, expert discussion on surprising dermatology findings. The hosts reviewed literature from practical pearls (tinted sunscreen, topical timolol) to quirky findings (tattoos vs. melanoma), all while offering plenty of clinical wisdom and real-world skepticism about overhyped results. The episode is a can’t-miss for anyone who likes their education mixed with laughter.

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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. Derms on Drugs is where cutting edge derm meets hit or miss comedy. I'm Matt Zyrus from Docs Dermatology and each week I'm joined by my residency buddies, Dr. Laura Faris from the University of North Carolina and Dr. Tim Pat from the University of Pittsburgh. 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 have some fun listening. New episodes drop every Friday on Scholars in Medicine, Apple Podcasts, Spotify and other major podcast platforms, and a reminder that the video component has the key figures or tables from the articles we talk about. So this week we're coming at you with one of our patented six pack episodes where we are going to be talking about the stuff that we found most interesting in the literature over the last few weeks or months here. And Dr. Farris, I'm going to kick it right over you to get us started.

[B]

Okay, So I picked for my first paper a recent paper in JAMA Dermatology. Successful treatment of alopecia areata with one JAK inhibitor after failure of other JAK inhibitors. And this is by Khalil, Craiglo and King. These are the JAK inhibitor alopecia experts out of New Haven, Connecticut. I'm going to give this title. This, this paper, the subtitle, how to hit the Jackpot for Alopecia. I know.

[A]

Now, before you go too far, we've kind of covered this topic before. So this is good. It's new. More information on it where we looked at people who, like, failed Barry and who failed Allumient and went on litfullo or vice versa or something. And I think the takeaway that we took then was that if the jack worked some, then there was a but not great switching. Had a good chance of working. But if the jack did. If one jack did nothing, then it was pretty unlikely that switching jacks was going to help. I think that was our. Our takeaway when we did an episode a few months ago. Does that sound right to you guys?

[B]

It does.

[C]

Yeah. I thought like the salt 100 people, which is basically like no hair.

[A]

Yes.

[C]

Right?

[A]

Yeah.

[C]

I always get confused.

[B]

Yeah.

[A]

Yes.

[C]

Is salt zero better. Salt 100. 100 is worse.

[B]

Yeah.

[C]

Yeah. Okay. Those patients typically didn't respond even after A switch, right?

[A]

Yeah. So if they got no better, they typically didn't respond. So it'll be interesting to see if this kind of recapitulates that.

[B]

Yeah, so this is definitely sort of a different. This is more of a case series. Okay, so just a reminder, you know, why does this matter? We now have three approved JAK inhibitors. Baricitinib, ie Illuminate, JAK1, 2 tick 2 inhibitor, ritlecitinib, ie Litfulo, JAK3 tech kinase inhibitor. Duroxolitinib, ie Lexelvi, JAK1, 2 inhibitor. Okay, so if you.

[A]

I didn't know a Lumion know Illumient got tick too.

[B]

I know. I didn't really either until I started doing a little reading on this and they said that it actually does. So I thought that was interesting.

[A]

Yeah, gets a little tick too. Okay, all right, good.

[B]

All right. And so in clinical trials, you know, we don't have head to heads, but we know 40, 45% of patients have a salt score of 20 or lower, which means you have 20% or less of your hair is gone at like roughly a year of treatment. Okay. So this was a retrospective case series out of Yale, so spanning 2014-23. 2023, it's only 13 patients with Seville. So what they did was they picked people with severe alopecia areata who failed one or more JAK inhibitors. So, you know, realize these guys were kind of the first people using JAK inhibitors. So they have, they were using not just the approved ones, but tofacitinib, Upadacitinib. And so what they did was they picked those people who failed one but then succeeded on another one. So it's a little bit of a different question. So what they did do was they said, all right, their key inclusion criteria was they had to have had at least six months on the Jak and that oftentimes their first line JAK inhibitor was sort of an off label one. So, you know, they didn't have the criteria of most clinical trials, like no concomitant therapy washouts, blah, blah, blah. So like 85% of these people were also on oral minoxidil, and about a quarter of them also got concomitant interlegional triamcinolone. So, you know, what did they find? So in, in every. All of these patients, they had failed 1, 2, and up to like 3 JAK inhibitors sometimes, and then they achieved a Salt less than 20. So these were sort of the people who were like the exception. So they actually had people who went from salt 100 to salt 0. One person actually went through four rounds. They went to four JAK inhibitors before they had hair regrowth. So, you know, the, the take home here was that resistance to one JAK inhibitor doesn't really necessarily predefine resistance to another. Does it predict it? Based on other clinical trials, we would probably say yes, but that it can happen. So, you know, this was like real world evidence. So I think it's worth it to move on to another JAK inhibitor. It also suggests that they're really not simply interchangeable, which is why I brought up the slightly different, you know, mechanisms of these drugs or different, you know, sort of, you know, sensit or specificities for the particular JAK subtypes. This was small, 13 patients. This was not a standardized protocol. Some they switched right at six months. Some, some were on for 18 months. Lots of concomitant therapy, you know, and so where, what are the weaknesses? So they do say, you know, we.

[A]

Know what the weaknesses are. By.

[B]

Well, no, but I will say there are data that would say, and we've talked about this in papers before, when do you give up? We actually like found that up to nine months, right? You can still see response. So six months is maybe too early. I think I would probably do nine. And you know, maybe the magic wasn't in switching, it was just in continued Jak inhibitor for longer than six months.

[A]

So the, the other interesting question we now, you know, we've talked about, we've got some Data that adding IMK, you know, once a month, 40 milligrams once a month for the first three months, like dramatically increases your response rate. Using clobatazole under occlusion can dramatically increase your response rate. So, you know, do you, would you start somebody, give them six months and if they're not doing better, think about doing one of those things or, you know, give them nine months. If they're not doing better, then switch them to another agent. And it's no easy answer to that. It's, it, you know, I guess you could talk to a patient about it and see which, which one they wanted to do. My guess is that adding steroid on whether topical or systemic probably has a higher faster response rate than does switching drugs. But especially if you're doing IMK or weekend dexamethasone or something like that, might be some risk with that.

[B]

Who knows, Maybe some. But you know, I also think it's hard to get patients switched. The approval process. I think it, I think it is worth it to give Them nine months, try adding adjunct. And then also, I thought this was just a good reminder. Like, add the oral minoxidil. I think when I first started using JAK inhibitor. I know when I first started using them, I didn't really think about that, but, you know, I think you add the oral minoxidil early and continue it on. Do you guys do that? When you treat with JACK inhibitors? Alopecia areata, do you also put them on oral minoxidil?

[C]

Not every patient.

[A]

Yeah, not at me.

[C]

Yeah, I like to go monotherapy. That's just my personal preference with everything. Like, find the one drug and then just do that one drug and max the dose before you add other things. Probably a different philosophy. I don't think it's any better. I just.

[A]

It's an interesting.

[C]

So if you don't have to use minoxidil, like, why?

[B]

Because it's so safe. And if you could have a higher dose of a JACK inhibitor or oral minoxidil and a JACK inhibitor.

[C]

I'll take a. I know I said it wasn't right.

[B]

I know. I'm here to beat that home. I am. Right. You are not.

[A]

It used to be an interesting question with, like, when methotrexate and cyclosporine were the only two drugs we had for psoriasis, would it have been safer to be on 25 of methotrexate or 10 of methotrexate plus 2 mgs per kg of cyclosporine? Yeah, like, probably the methotrexate, but maybe the. You know, who knows, right? It's an interesting question. All right, so takeaway. Switching jacks can help no matter how many jacks.

[B]

A third one or a fourth one.

[A]

Yep, yep, yep, yep. All right, let's go. Patton, what do you got?

[C]

My first six pack paper was from September 2025 edition of Aesthetic. Aesthetic. Aesthetic. No Aesthetics. Surgery Journal.

[A]

Okay.

[C]

Okay. It's called Comparative Efficacy and Recurrence Risk of Intralesional Therapies for Hypertrophic Scars and Keloids. A network meta analysis by Lie et al. So they performed a NMA on 24 randomized control trials for the treatment of keloids. They focused only on intralesional therapies of a study had, like, laser or cryo or other things. Surgery. It wasn't included in the analysis. So this was strictly IL and IL only. Figure 4 shows the forest plot evaluating efficacy versus tack alone and Botox, which, I mean, I've never done, but I was going like, there's Some decent data with Botox, but efficacy versus tac alone. Botox and tac plus 5 fu showed better odds ratios for efficacy when compared to other intralesional therapies like Bleo5 Fu alone and Verapamil, which I like vaguely remember, but I, I never did it and maybe I was thinking I remembered and it wasn't true. So odds ratios of 5 for Botox and 4 for the tack plus 5 fu compared to tack alone.

[A]

Does anybody actually do 5 fu inject like it's a chemo drug? So I think there's like this huge amount of like baloney that you have to do to be able to, to, to have it in your office and administer it at least I think, well.

[C]

You'Re supposed to draw it up in a hood and sterile negative pressure. There are all these sort of regulations about drawing it up. There's something called a 503B pharmacy. Does anyone know what that means?

[A]

Yeah, yeah, it's like it's basically a compounding pharmacy. But they can send it to you instead of sending it to the patient.

[C]

So people have done that. Okay, but I think there are a lot of.

[B]

Go ahead.

[C]

There's a lot of logistics to it and I think a fair number of providers are like, or I'm not dealing with any of that, or I need to know way in advance and get enough patience to make it worth my while to kind of get this all set up.

[B]

Okay, so 5fe is super cheap. Right. But it's the drawing it up part. So here at the University of North Carolina, and I had never even knew this existed, there is some like device you can put on top of the vial and draw it out. It's like a little makeshift like fume thing. It looks like a satellite TV dish and you have to like put it on and then you have a filter and you pull it up. But we do this. And every time I'm like, I don't remember how to do it. Can somebody help me? But we actually do this and we just have it in our, you know, non hospital based clinic with not without a hood. We have to draw it up through this special thing and, and the people who know how to do it, it's a little bit of a pain. Like it's got to go into a certain, you know, got to waste it into a certain thing. But once you have the, the setup, you can actually do this. So we do a lot of IL5 fu for skin cancer.

[C]

This sounds like several violations. And maybe we have to edit this.

[B]

Part of the no, it is not. We follow the rules at the university.

[A]

I mean, the rules are very different from state to state. It's a state based thing, so. Yeah, yeah, yeah, it might be, you know, yeah. Whether that's legal in other states or not, who knows?

[B]

I mean, we are like a state institution, right? Like we over follow every rule and it is that has been looked at and it has been vetted. So there are ways to draw this up in your office.

[C]

I'm just going to say maybe I will. Maybe, yeah, send me that information. Maybe we can start doing it. Figure 5 was a force plot evaluating recurrence. And the only treatment that showed a statistically significant odds ratio for recurrence was tac +5 fu when compared to tac. So it seems like tac+5 fu is better for efficacy, better for recurrence, Just the logistics of doing it. What do you guys do for keloids? I mean, with me, I do iltac. I think cryotherapy makes a difference too, so that I do those two ielts.

[B]

What strength do you do?

[C]

I. It depends on, you know, how many treatments they've had, the color of their skin. Sometimes you're doing TAC 10 and if they have darker skin, it starts to lighten a little bit, so you decrease it. I would say if I was starting brand new Keloid, probably TAC 20, like try and get as much in there as you can and really soften it. And then I, I don't think I go higher than that. I've seen some people that go as high as Tac 40, but I don't go higher than Tac 20. And then when you can kind of give them more and you start to see the atrophy and the hypopigmentation, uh, I'll take it down to Tac 10, Tac 5. Smaller lesions, kind of, you know, they come back and most of the keloid's gone, but there's the edge of it that hasn't responded. So maybe there I'll go tac 5. I mean, it just. Do you have a standard?

[B]

I don't have a protocol. It's a little bit gestalt, but like sometimes like, you know, on the back of the ear, those really firm keloids, they'll be like, oh, let's do TAC 40 for the first couple, just to try to really smush them down a little bit.

[C]

But yeah, and I, I do have a guy here at University of Pittsburgh where, you know, the earlobe keloids, where they're so Happy because you shave off this huge keloid and you inject and they come back for, like one or two treatments, and then they come back a year later and they have huge keloids for those patients. I. If they do that, I'll be like, well, we're going to do this a little bit different, and I'll do shaving them again and getting them set up for electron beam radiation therapy. So that's my, like, recurrent keloids. This thing came back because the patient got lost to follow up or whatever, and they still want them treated. I just say, all right, second time around, we're going to do electron beam. And there's a guy here that, like, does it. He. He likes doing it.

[A]

You're able to get that covered by insurance?

[C]

No, I, I suppose they do. You'd have to ask him. I mean, I, I just. They. They like to actually do it the same day of the surgery. So we coordinate the care where I do the shave and then they get radiation therapy.

[A]

Wow.

[B]

Wow.

[A]

Yeah, it's impressive. Nice work, Patton.

[C]

Hey, man. Okay, I don't have the little fancy 5 fu satellite disk.

[B]

I'll send you guys a picture of it next time I'm drawing it up. It's cool. Or next time I'm having somebody else draw it up because I can't remember how to do it, but yeah.

[A]

All right, let's move on to my. Got a couple of ones that I'm going to try and do quickly here. So, number one, this was interesting that if you get enough tattoos, it apparently protects you from melanoma. So this was done in Utah. They, you know, used their cancer registry when, you know, sent letters out to everybody who'd had a melanoma, got a 41% response rate, and then asked them about their tattoos. And it turns out that the people who got four or more tattoos had a over 50% reduction in their risk of any kind of melanoma or invasive melanoma. And people who got three or more large tattoos had a 75% reduction in their risk of any kind of melanoma or invasive melanoma. So this was a really fascinating. Because it, you know, what it made me think immediately, and they talked about this some in the, in this article was maybe if you get enough tattooing, it is kind of like immunizing people against some of the antigens in your epidermis. It obviously would be a very weak way to do it because if. If it was happening a lot, we'd see people get vitiligo and Stuff like that after tattoos. But that'd be kind of the next thing I, I'd be interested in. But maybe you're priming people's immune system so that when they get a melanoma they already have some, you know, reactivity. But it, it was interesting. You know, it's a single study, low response, you know, 41% response rate. Who knows? Maybe it, it is real, maybe it's not.

[B]

I'm glad it's a video podcast so people can see me rolling my eyes and pat and smirking at this study.

[C]

I didn't even, I'm like, maybe, maybe not. I just like the idea that I, that you went the next level. Like, huh, here's why, here's the mechanism. Was it, wasn't it just like, I mean, did they match for age? Don't younger kids have more tattoos?

[A]

Yeah, they did, they did matching and they did that.

[C]

Okay.

[B]

Race and, you know, healthcare utilization. I was like, well, maybe they're just like, you know, you're not, you're not biopsying all the little ditzel melanomas in situ because you can't see them because they're like all hidden in the tattoo. So you just don't have over diagnosis is the melanoma.

[A]

Well, that's, that's why they, that's actually why they broke it out to invasive and non invasive or to overall and invasive to try and make sure. And it didn't. So it's, it's something wasn't.

[C]

I thought I saw something about they just, they're more conscious. Skin care conscientious.

[A]

The main reason I thought this was fun is now whenever you're doing a skin check on somebody who's got a lot of tattoos, all of our listeners will be smart enough to be like, oh, you know, it's interesting that you have all these large tattoos that might actually reduce your risk of melanoma.

[C]

I know I'm gonna tell my patients to take nicotinamide and get three huge tattoos.

[A]

Right. All right, right on, right on evidence Anal medicine number two one that I did. So we did a melasma episode not too long ago talking about tinted or talking about tinted sunscreens. So there was a good study.

[B]

I don't know.

[A]

It was good comparison of visible light. Oh, I should say the title. The last one that I talked about was tattooing and risk of melanoma Population based case control study in Utah. This one was comparison of visible light protected protective tinted sunscreen to untinted sunscreen to protect melasma. Patients during summer, a prospective randomized investigator blinded study. So basically at 42 patients with melasma, half of them got regular sunscreen, half of them got. And very, very, very similar sunscreen that had some iron oxide and regular titanium dioxide. The one, the other one that was non tinted just had nano titanium dioxide. No other treatment. And what was fascinating was that. So the people who got just sunscreen, their melasma stayed stable over the five months of the study. There was no other treatment. As far as I could tell. The people who got the tinted sunscreen, their melasma got a heck of a lot better over the course of the summer, like impressively better as monotherapy. And it, it really kind of suggests to me that the reason we've seen melasma be so recalcitrant to hydroquinone and steroids and retinoids and lasers and everything else is that unless you're using a tinted sunscreen, you're not, you're not taking away the, the underlying problem. It was really impressive to me how well the tinted sunscreens worked as monotherapy.

[B]

So visible light is driving melasma. Right. That's what they're blocking is the visible light.

[C]

So, yeah, the question, did they have different skin types in this study or was it all like, fits, like 4.

[A]

And above, or 99% sure this study was done. So it was done in Europe, and I think they did actually report that somewhere. Let me look it up real quick here.

[C]

The question is because when we did those papers on visible light, I think it was pretty restricted to darker skin types and the visible light, the effect that visible light has on hyperpigmentation. So does that mean with like, light skin that has melasma, the tinted sunscreens don't matter then, that it's more driven by UV and not visible, or is it visible no matter what your skin type?

[A]

Interesting. I don't know. So, by the way, in this study, it was 93% phototype 3 and 7% phototype 4.

[C]

Okay.

[B]

Yeah.

[C]

Because now I'm seeing those patients, right, the darker patients. And I am mentioning tinted sunscreens, and you can match it to your skin color and there's some evidence, visible light yet to block it. But the lighter skin patients.

[A]

Come on, Pat. There's not some evidence. There is pretty overwhelming evidence to me at this point that visible light is a big factor in malaria, which is some.

[C]

I didn't say so.

[A]

So.

[C]

But I, I don't know what to say to the lighter skin, sort of brownish melasma people.

[A]

I could See, I, I have been.

[B]

Told that just instead I just tell them like for check because it's almost always women like just get a tinted sunscreen and make that like your makeup, your base routine for your makeup and then you're.

[C]

Yeah, I'm gonna.

[A]

Well here, let's, let's, let's move on here. And while Ferris is blathering on about some ridiculous article that's too complicated for me, I'm going to be looking for T screen for people with light colored skin. See what I can find online.

[B]

Sounds good.

[C]

Okay, go for it.

[A]

This is right.

[B]

Okay. Oh, do I get to gonna do like 18 papers?

[C]

No, no, no, you're good. He, he's doing two, we do one, he does two.

[B]

He's always twice as, you know, special as we are. So that all fits. Okay.

[C]

Exactly. Yep.

[B]

So I picked a paper from jadv. Depilumab shows no elevated risk for maternal adverse pregnancy outcomes by, I'm going to call PR et al, whatever that weird looking be that looks like a beta at the end of it. However that is pronounced in German. So sorry Dr. Prus, but you may be Dr. Pru. Okay, so we all know that, you know, we, a lot of times we have, we're treating, you know, women who are of childbearing potential with dupilumab. We don't really have like, we got like, you know, this general sense of well, dupixent's really safe and there's some good case reports. So you know, I think it's fine to be on in pregnancy. Or maybe we say I'm not super psyched about you being on this, we should switch you to topicals. But this gives us some, you know, kind of bigger data. So before this paper that I'm going to talk about, what was the largest study to date? It was 29 women exposed to dupilumab during pregnancy and they reported no significant, you know, drug associated risk or adverse pregnancy outcomes. So what was this? This is from our old friend Trinetics. So they looked at women aged 12 to 55 with documented pregnancy and you know, one of the type 2 inflammatory mediated diseases for which dilumab is FDA approved who received dupilumab during pregnancy. And then they created a one to one propensity score matched of, you know, pregnant women with, with similar diseases and comorbidities who did not get to dupilumab. So the primary window of interest was during pregnancy. But they also did some analyses for like dupilumab up to 6 months preconception and then in the pregnancy and postpartum periods, they looked at a couple outcomes for which that might have mattered. So final cohort 200, 293 dupilumab exposed pregnancies matched to 293 controls for the in pregnancy analysis. And, you know, matched as much as they could. Like demographic, pretty well matched for comorbidities, demographics, other concurrent medicines like steroids, other biologics, et cetera. So, you know, what they looked at were, was a composite measure of maternal adverse pregnancy outcomes within 270 days of pregnancy diagnoses. So these were, you know, preterm labor, gestational hypertension, proteinuria, gestational diabetes, spontaneous abortion, and genital urinary infection. So these Kaplan Meier curves. Yes.

[A]

Were these just women who stayed on DUPY through pregnancy, or was it like, if you were on dupy, got pregnant and stopped it, you know, at week four, you know, as soon as you found out you were pregnant, Could. Were, were they still included or was this people who stayed on it through pregnancy? Did they specify that?

[B]

Not. I mean, they had to be. They had pregnancy exposure. I gotta be honest, I'm not sure how long. If they had to be on the entire thing. For some of them, they were because they also had this cohort that was on like throughout and then up to six months after. Okay, so I don't know how long you had to be. I can.

[A]

All right, let me.

[C]

Yep. I'll.

[A]

I'll see what I can figure out here.

[B]

Okay. So the, the top line. Results, Results. No elevated risk of any maternal adverse pregnancy outcomes that they looked at in patients treated with dupilumab. Now, they also did look at women who had type 2 inflammatory disease. You know, they had this group that was overall and. And the dupilumab. And so one of the things that was interesting was that there was actually a reduction in some of the adverse pregnancy outcomes, so specifically in those women who got dupilumab. So specifically, if you had type 2 inflammatory disorders and you were on dupilumab, you had a lower risk of preterm labor hazard ratio, point 11, which is pretty significant. And if they looked at the composite, like any adverse pregnancy outcome, that hazard ratio was 0.53. They also looked at breast infection. So I think this is like, do you get mastitis if you stay on depilumab? And the post pardon period? And there was no increase in that either. So, you know, large database propensity score matching, you know, an important result. So, you know, what are the limitations? So this is prescription records. So Adherence and exact timing are uncertain. You know, they said in there. And then you're of course, like depending on coding. And then really, I think the key weakness here is that they did not not look at neonatal or child long term outcomes. So this is only maternal records. And they said like for privacy. I think it's probably because it's really hard to match. So what we don't know is like, what happened to the babies. Right. Did they have any problems with, you know, development? Do they have any issues? Did they not get into Ivy League colleges? We don't know. So, yes. So we can say this is reassuring. We can't say this is 100% safe. But, you know, the things like preterm labor or spontaneous abortion are concerns. And the fact that that was a little lower I thought was interesting too.

[A]

Okay. It's an interesting thing to keep in mind that there is a risk of having especially uncontrolled type 2 disease, you know, through pregnancy. So it's not like there's not a downside to stopping it.

[B]

Yeah, right.

[C]

Yeah, I thought that was into that. Figure 4, which is basically increased risk for adverse pregnancy outcomes in patients with type 2 disease compared to patients without. So if you have a type 2 disease, no matter what it was, asthma, esophagitis, they actually have worse pregnancy outcomes compared to people that don't. So.

[B]

Yeah, so there's like two cohorts.

[C]

Strongly encourage them.

[B]

Yeah, yeah. Treat. At least treat your. Yes, treating your disease makes sense.

[A]

And they said in the article the reason you. So the reason you didn't know is that they had a throwaway line somewhere in there that said we couldn't tell if people stayed on it through pregnancy or stopped it.

[B]

Yeah, no, and they kind of said that as a weakness. Like, we couldn't. We can't really tell the timing. So. Yeah, because I think they have prescription data, but not necessarily like they don't have administration data. I don't even know if they're filling data.

[A]

Yeah.

[B]

So, yeah.

[A]

So the most important thing here is it tells us that it is safe to be on DUPY while you're trying to get pregnant. And then what I'll probably be doing is telling people, you know, if they get pregnant or doing great on dupy, like the data suggests, there's no risk and it might be beneficial to stay on it. But you know, what I would probably do is hold your dupixent and then if your eczema starts to come back, the second it starts getting worse, restart your dupixent. You know, see if I can get them off, but then don't let them get a whole bunch of type 2 inflammation going on. Which, you know, is where I think the risk probably comes in.

[B]

Yeah. And I think it's also important to remember that like you get active transport, transplacental transport of antibodies around and I don't. It's like, it's. It's well into the second to close to third trimester. Right. So like you really shouldn't be getting trans placental transmission of an antibody like dupixent early on. So, you know, I used to think about, I mean, I not used to. I think about this with women in psoriasis. If you have a drug that's dosed every, you know, two or three months, you know, maybe just avoiding the last few months of pregnancy and dosing means that you have minimal fetal exposure, but you still, you know, probably don't have bad disease activity. So I think that's another important consideration. So first 12 weeks you're not getting exposure anyway.

[A]

It'd actually be an interesting topic to have a guest on to talk about treating women with, you know, managing the woman of childbearing potential and the woman who is pregnant because it really is, you know, changes the discussion a little bit. Whenever you start to think about that there is probably not even. Probably there is risk to having uncontrolled disease. So it's not like, well, we should stop the drug to be safe. Stopping the drug might have be like, yeah.

[B]

And of course there are drugs where this is not the case. Where, like methotrexate, Obviously not the case. Back inhibitors, very clearly not the case. We gotta make sure that those are stopped.

[A]

But biologics. Biologics, basically what we're talking about.

[C]

About.

[A]

Yes. All right, let's move on. Patton, what do you got?

[C]

All right, second six pack article, August 2025 edition of the BMJ titled Efficacy and safety of Anaphon and Reopon. I don't know.

[A]

Need to stop letting you pick your own papers.

[C]

Damn it. I don't know why I picked this one. This is more for renal people, but let's just move on. Efficacy and safety of an RON in patients with pritus undergoing hemodialysis multicenter, double blind, randomized placebo, controlled phase three trial. They. They misspelled hemodialysis multicenter and randomized in the title. It was by Lou et al.

[A]

Not that's called proper English.

[C]

It was not Rebecca Lou. She was a third year resident. She just graduated. So I saw that Name. I was excited it wasn't her. Uremic pruritus very hard to treat. Don't really know what causes it. Maybe an imbalance of kappa opioid and mu Mu mu.

[A]

There you go.

[C]

Mu. Opioid receptor signaling. More moo. Opioid receptor activation. That's why morphine can make people itchy and you have a downregulation maybe of kappa opioid receptor signaling. So somehow peripheral kappa opioid receptor activation can decrease the sensation of itch. So there are two kappa opioid receptor agonists that are available IV diffilic.

[B]

3 hour AD boards on diethylcaphalin.

[C]

Diphyllo Cathaline was approved in 2021. It's given as an IV medication three times a week. With the patient's hemodialysis there's actually an oral kappa opioid receptor but that's only available in Japan. Anyway. This was a multi center double blind randomized placebo controlled trial. Patients got either in a and ricathon 0.3 mics per kg IV three times a week or placebo for 12 weeks. And then there was an open label 40 week where everyone got drug. Primary endpoint percentage of patients achieving a reduction of 4 or more points in a weekly mean 24. Worst itch numerical rating scale score from compared to baseline little over 250 patients in each group. Primary endpoint was reached by 37% of patients receiving the drug compared to just 15 in the placebo. This was statistically significant. Secondary endpoints similarly statistically significantly better for the Anarika Fawn compared to placebo. Adverse events were similar between the two groups in the double blind. Maybe more dizziness with an Ricaphon. I just wanted to revisit kappa and mu opioids and their role in itch. And this is more often obviously going to be managed by their renal docs. You know it's weird, I will say I haven't seen uremic pruritus in a long time and maybe that's because more and more of these patients are getting these kappa opioid receptors and so we don't see them anymore.

[A]

First the diphelic is reasonably new drug. The last couple of years it's been on the market. I think the renal people just kind of stopped sending them to us because we weren't much help.

[C]

The.

[A]

The, you know the, the, the, the practical aspect of this whole topic. The kappa and mu opioids is intranasal butorphanol which is the, the most effective itch drug we had Prior to Doopie and Nemo, I really, it's, it's gotten so hard to write opioids, like, I don't know, use it anymore. But that was a, it's a combined Kappa agonist Mu antagonist. It's almost impossible. It's extremely hard to get like hooked on it. You don't get withdrawal, nothing. But it's still really hard to write because it's an opioid. But it, it, for most people, it worked really well for itch.

[C]

Do you, have you seen Doopy Nemo work on like consistently well, not work at all in uremic pruritus or do you see a mix of that small.

[A]

Number of patients that I have seen, but that has worked well and it's in the literature as well as working.

[C]

Well, it seems like it was small case reports. They have like a case series on that.

[A]

I, I, I'm pretty sure there's a case series about it, but I am not 100% sure.

[C]

And you're talking both Doopie and Nemo.

[A]

Nemo. I don't think there's anything in the literature about it, but I'd be flabbergasted if it didn't, if it didn't work. And so there was a, In August of 2025, there was a retrospective observational study looking at DUPY in renal pruritus. Shoot. I cannot. But what I remember from looking at that and I'm okay, good. I just got it pulled up. It works very well. But let me pull it up here and see if I can get a.11 of 12 patients. After eight weeks, 11 of 12 patients experienced at least a three point itch reduction. Now it's open label, not randomized, blah, blah, blah. So there's, you know, significant placebo effect or whatever, but it worked very well in them. And it may have been, let's see, I don't know if these people had to have atopic dermatitis as well. Doesn't look like they did though. Okay, so yeah, 12, 12 patient case series at least.

[B]

All right, so it's a maybe.

[C]

I'm convinced.

[A]

Yep. Yeah, should work. All right, moving on to my last two. So first one was an open labels thing about Jack inhibit oral JACK inhibitors for vitiligo. Main takeaway for me was not that impressive. So this was a retrospective series. They had about 96 people who got either Tofa or Rinvoak or Riddle or, you know, what are the JAK inhibitors we know about? Let's see here, about half of people got 25% repigmentation only 10% got 75% repigmentation and most of them had concomitant therapy as well. So most of them were getting narrowband UVB and topicals and whatever. So the, the biggest thing though was that assuming they do work, which I do think, I think they do, it's very duration dependent. So when they looked at if people got at least 25% repigmentation. So like anything, if you were on the jack for three to six months you had about a one in three chance of it working, getting some repigmentation from six to nine months. Now you were like okay, almost two out of three, we're getting some repigmentation. Same thing up to 12 months, still two out of three. Up to two years it was still two out of three. But then by the time you got to more than two years, of the four patients who had more than two years, three out of four had at least some repigmentation. Now some of that is wrong.

[B]

That's too long. I think nine months is our jack window. 66 to 75% get it.

[A]

I would, yeah, I would, I would agree in the two year number. Right. While I was like well three out of four who did for two.

[B]

Yeah.

[A]

But for people who it wasn't working after a year and a half and dropped out like they're not going to show up in here. Right. So there's, but the, my main takeaway was I was kind of expecting them to work better.

[B]

And they question with the Jackson vitiligo is what happens if you do repigment, can you stop it? Or is it like alopecia areata where you lose all your hair? I think that's going to be.

[A]

Right. And then is it like the same thing with narrowband uvb? Right. If you do narrowband UVB and somebody repigments, if you stop the narrowband uvb they're likely to depigment again. And, and these numbers that I'm talking about, the majority of these people were getting concomitant narrowband uvb. It's going to be really interesting when we start to get the phase three trials reporting their data with you know, Jacks as you know, standalone therapy and vitiligo. Do, do they work? And I really, I, I don't know if oral jacks are going to work or not. It's an interesting question.

[C]

Yeah, I, I'm curious like I know how much it impacts patients especially when it's on the face and I think that's probably that can be very difficult to, to live with. Are they had like, if they got 50 better, are they like, you know, this is actually easier to manage. I, I have to put less cover up makeup or are they like, this didn't get rid of my vitiligo. I, I'm just considering it to be not working.

[A]

I don't know that they did like fazzy or anything. Quality of life stuff in here. Yeah, let's see here.

[C]

Even when they show like Opsalor, I mean, you see, I've seen these lectures on Opsalor and they're like, look at how much better their vitiligo is. And I'm like, yeah, but they still have vitiligo. Like you took a patient that had vitiligo and turn them into a patient that has vitiligo. It's. It's better. But you would never, that person would never walk in the room. I mean like psoriasis. It's like you can take somebody who has psoriasis to like, you don't have psoriasis for all intents and purposes. And with a lot of the vitiligo therapies, you're not doing that. You're. You're not getting rid of the disease. And so what are patients going to be willing to expose themselves to? What sort of risks are they going to be willing to expose themselves to? Vitiligo is very. And there are some patients that their vitiligo truly does not bother them. So it's just, it's a very interesting. We could have a whole deep dive on vitiligo. We should do that one.

[A]

Well, we should do that at some point. That, that would be good.

[B]

No, with a patient. The patient reported part would be interesting.

[A]

All right. And then the last one is, is just a case report, but I know there's ongoing work with this. It's interesting. So topical timolol eye drops. Right. Are used, I don't know, for something ophthalmologically, but they are cheap and they have some kind of interesting vascular effects. Right. So we know they work on infantilemangiomas. They seem to have some benefit in red scrotum syndrome. There's also some evidence, so there's actually pretty strong evidence that they really help with healing of chronic wounds. This is. There's also a report of them helping with the chronic fissures and erosions of hand eczema. And that is usually the hardest part of hand eczema to get better. So especially with the new topical jacks that we Have. But this would make a lot of sense as an add on therapy to a topical jack or whatever you're using. If you've got people with recalcitrant fissures or people who get the little fingertips fissures and cracking. Topical Timolol is cheap, easy to get, and you just put a drop on the fissure, you know, one to two times a day, and it may make a big difference for people. And there are the, the, the beta adrenergic receptors are present on keratinocytes. So it certainly makes sense from a, you know, mechanistic perspective.

[B]

Yeah. I thought that was cool. That was my maybe favorite paper. I was like, because you just want something you can do for these patients.

[A]

Yes.

[C]

Haven't you, have you ever patch tested really bad eye lid dermatitis to their drops? And haven't you seen positive past reactions to Timolol?

[A]

So Timolol can cause allergic contact dermatitis? I think the probability of, you know, inducing contact dermatitis by doing this. So I could see it more if you were using it on, like, stasis ulcers, which is why I'm a little hesitant to, like, talk about it in lower extremity wounds. But, yes, it exists, but it's, like, vanishingly uncommon.

[C]

I. I just remember testing, and of all the things she was taking, she had, like, antibiotic drops and all that. I'm like, the, the Timolol is such a benign whatever drug that's never going to cause a reaction. And her reaction was horrible.

[A]

Yeah. The interesting thing to patch testing ophthalmic. Ophthalmic drugs is that you want to kind of abrade the stratum corneum, like vigorously rub it with gauze or something before you put the patches on. If you're testing to their drops directly.

[C]

In particular, you said stratum corneum, and I heard cornea. I'm like, man, you do that, but.

[B]

You get to the right answer. They're blind, so it doesn't matter.

[A]

I don't need the doctor back.

[C]

Please sit still. We're. We're patch testing, man.

[A]

That's a whole new approach for getting your vitiligo patients better. Patton, right? Oh, it's. Yeah, you're better. It's totally cleared up. You're good because you blinded them. And then one last thing just to throw in. This was funny to me. So a journal called Skin Research Technology one day had like, 15 articles that they retracted that were all Mendelian randomization studies. And there's just. It is interesting. So I've done a lot of kind of digging at times into Mendelian randomization studies to see if like they're really believable. And as a general rule I would say they're not in very specific instances, I think they can be where there's like an obvious like this and this are clearly associated. Here's how they're associated, here's the biologic mechanism, here's the whole thing. And now we can. This Mendelian randomization will maybe help us figure out is it causative or not. But people use them all the time for all kinds of stuff and yeah, it was just interesting. A whole bunch of them retracted. Just. Yeah, interesting. But so we're, we're going to stop it there for the week. I want to thank all of our listeners for joining us today. Today I hope you learned a few things. Hope you laughed once or twice. Mostly we're 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 Drugs.