← Derms on Drugs
Derms on Drugs
Litfulo Lowdown: When to Wave Goodbye; Olumiant Showdown: Solo vs. Squad; Solar Shocker: More Sun Equals Less Death?
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- [00:18]
A
Welcome to Derms on Drugs, a new video podcast brought to you by Scholars in Medicine. Derms on Drugs is where cutting edge Durham meets mediocre companies. I'm Matt Zyrus, nowadays a private practice dermatologist in Columbus, Ohio. And each week I'm joined by my residency buddies, Laura Farris, who is now the chairwoman of dermatology at the University of North Carolina, and Tim Patton, who is faculty at the University of Pittsburgh, to use our 60 years of combined experience to discuss, debate and dissect the hottest topics in dermatology. It's everything you need to know to be on the cutting edge of dermatology. And it'll be the most fun you've ever had while actually learning something useful about dermatology. So tune in every Friday only at Scholars in Medicine. And with that said, we're going to jump into the first segment of our show. So, as you may know, we break our show down into the big three, where we talk about our three favorite articles of the week, then we go into our deep dive. And I could not be more excited to have somebody on who is going to hopefully make you have thoughts that you have never had before about the topic of ultraviolet light and its health impact. And then we're going to talk about a few more articles after that. So let's go ahead and get into it. Laura, I believe you've got our first article today, so go ahead and jump in.
- [01:44]
B
All right, so I am going to be talking about a publication that was in JAD, sustained hair regrowth with continued ritlecitinib through week 48 for patients with alopecia areata. So this is a post hoc analysis of the Allegro Phase 2B3 trial. So what did this show? So, you know, the first thing it showed was sort of what you might expect, which is that most people who are responders at week 24 still respond at week 48. So, you know, important to show. But I thought not the most interesting part of the study. I thought that the most interesting part was looking at what happens to people who are not responders at week 24 and if you continue them on drug, what happens at week 48? So if we define non responder as patients who do not achieve a Salt score of 20 or less. So salt score meaning the extent of your hair loss. So if they didn't reach only 20% hair loss, those were considered non responders. So first of all, who were these people? So you're less likely to be a responder if you're male. If you've got more extensive AA at the start, meaning either you had a higher salt score, like maybe a salt 100, you had complete hair loss, or if you had alopecia totalis or universalis universalis, longer duration of disease. And also if you had more eyebrow and eyelashes loss. And so, you know, what we can see is that basically a quarter to a third of non responders at week 24 actually did respond if you went out to week 48. And we also saw, you know, better eyebrow and eyelash regrowth too, from week 24 out to week 48. So, you know, can you determine who these people are going to be? Should you just say anybody should just go to week 48? It turns out that if you really saw like almost no hair regrowth at week 24, you weren't going to miraculously see a great response at week 48. So, you know, in general, you're looking for those people who may have, you know, 40, 50% of regrowth, but they haven't, you know, reached that salt 20. And so those are the people. So I thought this was helpful guidance. I think it's also helpful in terms of counseling patients. What do you guys think?
- [04:08]
A
So I thought that it was super useful to know that if you've had nothing at six months, it's basically probably time to switch up and try a different agent or do something else. And the other thing that's just fascinating me about alopecia areata is what a strong correlation there is between severity of disease and duration of disease in response to therapy and how that's kind of different from other diseases in derm that I don't think of it as being, oh, you've got 50 BSA of psoriasis, so you're less likely to do well, or you've had psoriasis since you were 30 and you didn't get it till you were 70. Like, it's been interesting, but that, that six month cutoff I found super useful.
- [04:55]
B
Patton.
- [04:57]
C
Yeah, except those curves were, they were still going down, right? I mean, we don't have any other options, right?
- [05:03]
A
Look at bear sitting this if.
- [05:06]
C
Well, so fine. But I think, you know, they're comparable JACK inhibitor, very close to the Jack mech or whatever they're. They're classifying real acid in a bass. I, I think if the patient was tolerating it and they, you know, they probably maybe have a little bit of peach fuzz, I think I would probably keep them on it. Right? I mean, we've seen this with the JACK inhibitors At alopecia area, it takes forever.
- [05:33]
A
I'm going to give you the two secret Zyrus hacks for alopecia areata. And these are relatively literature based. There was one study of eight people with alopecia universalis and totalis who they started all eight on prednisone along with Barry, tapered the prednisone over three months and all eight regrew and then maintained. And then there's also some good data looking at AT&AU using them using clobazole under a swim cap until you start to get regrowth. So now my. Because I didn't want to do either of those at the start, but now my spiel is if it's six months, you're not getting better. I'll add three months of prednisone or I'll try the clobatas all under occlusion.
- [06:16]
C
Yeah, sure, that makes sense. And I wonder, you know, topical immunotherapy, adding that to Jax, that seems like because they're anti inflammatory, maybe it would make that less effective.
- [06:27]
D
I don't know. Right.
- [06:29]
A
All right, let's go on to our. Let's go. Ferris, anything you want to finish on that one?
- [06:34]
B
No.
- [06:34]
A
All right, Matt, let's go on to our next one.
- [06:37]
C
All right, big three. Paper in the January jamaderm by Seneschal et al titled combination of baricitinib and phototherapy and adults with active vitiligo. A randomized clinical trial study was conducted in four hospitals in France. Consisted of 49 patients with active non segmental vitiligo. That did seem to be important. The patients either had to have new or expanding patches of vitiligo within months.
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A
Okay.
- [07:00]
C
They also had at LE5% bodice body surface area and the presence of hypochromic aspect or perifollicular. Like they really kind of selected these for like. These are active. Yeah, active. Active vitiligo. 12 patients took placebo for 12 weeks. 37 patients took Barry 4 milligrams for 12 weeks. And then both groups got into the narrowband.
- [07:23]
A
Did they have narrowband the first 12 weeks also?
- [07:26]
D
No.
- [07:26]
A
So first 12 weeks were just placebo or drug. Then at 12 weeks everybody started narrowband.
- [07:34]
D
Right.
- [07:34]
C
And they continued to take either placebo or the baricitinib. All right, so the figure. Figure 2 shows improvement in the mean vasi in both groups. It's better in the berry. So a mean of, you know, 44.8% improvement in the VASI mean VASI compared to 9.2 in the placebo this was, you know, measured at weeks 30, week 36. And the supplementary material, there were some clinical photos showing improvements. And these were like obviously cherry picked by Eli Lilly. But you know, basically the person who got the placebo plus light. Her, her, her. This was a face. Vazi got worse. The other two had pretty decent responses. I thought it was interesting that the bottom picture, you could see the effect that goggles have on eyelid repigmentation.
- [08:22]
A
Never occurred to me.
- [08:23]
D
Goggles?
- [08:24]
C
I'm assuming that they didn't spec. I was looking for the protocol.
- [08:28]
A
Has to be.
- [08:28]
D
Yeah.
- [08:30]
C
Figure three, top three graphs, different measures. They had Vazi 50, Vazzi 75, face Vazzi 90, all of which better in the Berry group. And then figure 3D shows DLQI, which is about the same at 12 weeks. So that's kind of funny. Barry and, and placebo, uh, they both had slight improvements. And then you started to see a little bit of separation. It looks like 24, 36. It was a good separation, but the text says that it was only statistically significant at week 24. Interestingly, the other quality of life measures didn't show any difference between the groups. And then I think the. One of the big things they kind of brush by in the text because they're like adverse events was about the same, but one of the subjects in the Berry group had a pulmonary embolus.
- [09:18]
D
Hmm. Okay.
- [09:20]
A
So.
- [09:20]
C
So my interesting systemic jacks taking on vitiligo here in the US someday.
- [09:27]
A
So I just started doing the ritlecitinib trial for this and I'll say it is slow. So I'm not surprised nothing happened in the first 12 weeks in the Berry. Right. That their quality of life didn't get any better. I was mostly shocked by how lousy narrowband UVB worked on its own that 24 weeks twice weekly. So. But, but what you said of them selecting per people with perifollicular, people with some leukotricia. That makes more sense.
- [09:56]
C
Yeah. So that, that was their theory was Barry's going to stop the active disease from progressing. Then you hit them with a narrow band that's going to allow the repigmentation and things like that that we usually see.
- [10:07]
A
So yeah, and it makes sense to put together something to stop the immune attack and then something else to stimulate the melanocytes. Ferris, what are your thoughts? Anything?
- [10:16]
B
Yeah, I thought it was interesting. I have not done obviously, well, maybe not obviously systemic JAK inhibitors for vitiligo. I've done topical. I have found that they work better if I do it together with either eczema or narrowband. So it kind of supports that. I think to me, the question will be when do we go to a systemic jack versus a topical. But putting it together with uv.
- [10:41]
A
And just out of an interesting thought, it makes a lot of. I'm doing now for my primary treatment for facial vitiligo Opzelura. And then I'm using topical bimatoprost together with it because you can get the little generic bottles of bimatoprost eye drops, like really cheap. And so for three months, try and stimulate your melanocytes with that in addition. All right, so let's move on to our final big three article and this one, our first two were really looking at therapeutic interventions and how to use them most effectively. This one is totally different. And I'm so excited to go into this with our deep dive guest who is one of the authors and who's driving all this work. So higher ultraviolet light exposure is associated with lower mortality. And analysis of data from the UK Biobank cohort study. And so essentially, you know, the Biobank is, to my understanding, about 500,000 people that they've, you know, drawn blood, have genetic sequencing if they need it. All of these health questionnaires, they know their social determinants of health, like, like they are a very well categorized group and it makes it incredibly powerful because then you can really match people very well based on, you know, other potential confounders and hopefully rule them out. So that is what they did in this study. So they compared people, either people who said they used a sunbed, a sun, went tanning and then followed them over. I think it was about six years on average. And they also looked at the average UV radiation where you live based on sunlight. So using satellite data and that kind of stuff. And they showed a pretty dramatic reduction in all cause mortality with either tanning bed use or living in areas that have more sun. And it was kind of a linear relationship, this tanning bed use. We didn't have data on how much they use the tanning beds, but with the sun UV we did and there was a relatively linear relationship. The biggest effect is on cardiovascular disease. There's also a significant effect on cancer disease and cancer deaths and even on non cancer, non CVD deaths. So on every marker it improved overall survival. Now when we talk about skin cancer specific survival, the people who use the solarium or got more sun did get more melanoma, but they were, they were no more likely to die from melanoma. And so it, you know, the question becomes, do these advantages. So first, if these advantages in. When I say if, like, to me, it is very well proven now, but if these are real, which I believe they are, if they outweigh the, you know, the number of deaths from melanoma, it may turn out that it's a, you know, there's this risk benefit where it's actually, we should be telling people, get more UV might increase your risk of skin cancer, but it's gonna reduce your risk of dying from all this other stuff even more that it increases your skin cancer risk. And you can't get it from vitamin D. So vitamin D doesn't help with any of this stuff. And that's one of the crucial parts. So before we have our guest on and kind of start going into this whole topic bigger because there's a long body of literature on this, that this is sort of the capstone of Pat and Ferris. Any initial thoughts on this?
- [14:25]
B
I thought vitamin D is really more of like a biomarker of UV exposure than the, you know, what is actually mediating the response. The solarium use is tough because somebody has used a sunbed once versus, you know, has one in their basement like we see in the U.S. those are two very different, you know, two very different exposures. You know, I think it's. I think it's interesting. I think it's also really hard. There's collinearity, probably with using a tanning bed or being outside a lot, or tanning and exercise and some other things.
- [15:01]
A
I think they controlled pretty well with that stuff. I think they.
- [15:04]
B
I think it's hard to fully do it. It's hard to fully control for those things. But I know, I agree. I mean, I think it's very interesting. A patent.
- [15:14]
C
I think it's interesting. And, you know, I started to think, all right, I totally, completely buy into this. How would I change my life? I wouldn't change anything. I mean, I'm not horrified of the sun.
- [15:28]
A
What about your patients? What are you going to tell your patients?
- [15:31]
C
I think that you risk stratify. And I think that, you know, this was kind of brought up in the Australia, I think in January last year. January, February last year, they basically risk stratify their patients and they counsel them based on what type Fitzpatrick you are. It's a more reasonable counseling that I think makes more sense as opposed to just maybe saying what we tell our patients. You need to protect yourself from the sun and uv. That's the most important thing. But I also do think that America is Not England. There was another study out of Sweden. Like we just aren't the same as in terms of our sun exposure. So.
- [16:20]
D
Right.
- [16:20]
A
Is that, is it relevant to people who live in North Dakota only or is it also relevant to people who live in Ohio and Pennsylvania and North Carolina? Right, that. That's the other question. Well, let's. From there, because we got some interesting questions that I think we've got probably the best person in the world to answer them. So I want to introduce Dr. Weller. So he's Professor Richard Weller, dermatologist at the University of Edinburgh, who has been doing this work for decades. And I think every possible argument against it he has heard repeatedly. And I really can't wait to get into this. So, Dr. Weller, the first thing that I really want you to start with is because we got to get people to buy this as possible and so to start, explain the mechanism by which UV reduces cardiovascular morbidity and mortality and if vitamin D supplements help. And we're going to really stick to cardiovascular because I think that's got the best data. But let's start with that question. Just take your vitamin D pill and stay out of the sun.
- [17:32]
D
Yeah, Matt, great, thanks. And look, it's great to be here. I spent two years in Pittsburgh doing research, which is actually where a lot of this started off. So it's great to be back with some Pittsburghers discussing this. So. Yeah. So mechanisms. Well, I think so. I suppose the first thing to say is vitamin D is being hugely overplayed. It's got some benefits. It prevents rickets. And there's all these observational. Yeah, so there's all these observational studies. People with higher measured vitamin D levels are healthier in pretty much every way you can imagine. But correlation is not causation because we've now got the results of all the clinical trials. The biggest single one, of course, run in America, the vital study, the biggest of all, run by nih. And actually when you give people vitamin D, it doesn't do much. As you said, Laura, it's a biomarker for sunlight exposure which prevents rickets in children and probably doesn't do very much if you're going to believe randomized double blind placebo controlled clinical trials, which I think are a powerful tool that we should listen to. So if it's not the vitamin D, what could it be? And the mechanism I've really discovered is this nitric oxide release. So it turns out that the skin contains large stores of nitric oxide. I was studying this down a blind Alley in Pittsburgh. If you watch TED talks. I gave a TED talk on this. And we found the skin contains large stores of nitric oxide which have released which are photo released by UV when it hits the. When it hits the skin.
- [19:16]
A
A or B.
- [19:18]
D
Well so interesting in us in my original studies we use uva. That was really to show this was a vitamin D independent effect because vitamin D is made by UVB and I wanted to show that there's a vitamin. This is a vitamin D independent thing. So I used UVA lamps in my human studies. But I suspect UVB is actually as important if not more so. But we discovered it releases no into the circulation vasolylates, lowers blood pressure and high blood pressure is the biggest killer in the world today. You know, it accounts for. It's 18% of all deaths in America are directly related to high blood pressure. And we also showed then in later studies we did in America that actually skin color really matters. So we looked at dialysis patients mostly because they get their blood pressure measured three times a week, week in, week out, year in year out. And we took a data set by the Fresenius who run most dialysis units in America. And they've got 350,000 patients on dialysis in 2,000 different centers in America. And we could look at their blood pressure three times a week over three years in 2,000 different centers. We could then look at effects of wavelength UVA and B we could look at skin color. Really importantly we can look at temperature. And what we showed was that more UV lower blood pressure important. But that fall in blood pressure was much less marked in black Americans than white Americans. And of course skin color determines our response to uv. That's what it's about.
- [21:04]
A
Did you guys so were able to rule out in that that temperature wasn't the issue because you hear that all the blood your skin to your skin when it's warm. So you get. But that didn't show the same.
- [21:16]
D
We did indeed. So look. So about half the seasonal variation is due to temperature, but about half of it is independent of temperature. Okay. And that's really important. So it's not vitamin D. The clinical trials show that about half of it, about half of seasonal variation is temperature, but half of it is UV independently of temperature.
- [21:41]
A
I'm going to Laura, what do you. What's your. What's the first question you've got for Dr. Weller?
- [21:45]
D
Laura?
- [21:46]
B
You know I. I can understand. I mean I think that the data are interesting. There's a plausible mechanism for this. I guess my Question is like, how much does it take? Right. So patients always say, like, oh, I'm not. If I. You know, they're always worried about making vitamin D, which I think we can say that's actually not what you need to worry about. But it's like, what's, what's the dose response here and how, how can you get to it?
- [22:13]
D
Yeah, look, so the answer is we don't know because we haven't done the experiments. What I would say is that in northern Europe, the seasonal variation in blood pressure, so the difference between winter systolic blood pressure and summer systolic blood pressure is about 6 millimeters of mercury. Now, so if you were experiencing summer levels of sunshine instead of winter levels of sunshine, that would lower your blood pressure by 6 millimeters of mercury. Well, what does that mean? Well, that means a reduction in your risks of death from cardiovascular disease of 23%. That is huge, because cardiovascular disease is the biggest killer in North America, Europe and the world now. And this is huge. And so we have this. Look, it's currently mid winter here in Britain. We are having our usual winter bed crisis. When I was a young doctor, every winter you have a bed crisis. I have to say, the modern NHS, we have a bed crisis 12 months a year, but it used to be a seasonal thing and it. Progress, progress. We love it and we know that people are sicker in winter. Hippocrates described this two and a half thousand years ago. There's a kind of culture as an internal medicine doctor in Britain, that you don't take your holidays in winter because it's bad form, because everyone's bloody busy and if you're on vacation, you're dumping your colleagues in it. It's an unstated rule. It's just how the world is. And so nobody thinks about it. Why is everyone sicker in winter? Hippocrates observed it didn't explain it. And it looks like for cardiovascular disease, a big part of it is sunshine.
- [23:58]
A
All right, I got to ask this because I follow this literature pretty carefully, Laura. So there was that Korean study that people getting narrowband UVB for vitiligo got a 30% reduction roughly in cardiovascular. And that made me think, well, looks like getting two minutes of narrowband UVB two or three times a week is probably enough if you were to use this interventionally. If somebody was to be like, hey, Doctor, well, we think there's a trillion dollar business in America. People all love to be tan. We can't get them out of those damn tanning beds. Anyways, let's make narrowband UVB tanning beds. How often do you think people should go in to get most of the benefit?
- [24:44]
D
Yeah, really interesting. And I know that study very well. I reviewed that for the jid. So it was sent to the. Am I allowed to say this? I reviewed it, you know, years back when it came out and it was submitted to the jid. And I have to say it was really poorly analyzed when they first did it. They looked at people who had. So they compared people that got their vitiligo treated with narrowband UVB phototherapy versus people who had it treated with topical steroids and they took it from the health data in Korea. And the great thing about vitiligo, if you're looking at psoriasis, they've got so many bloody comorbidities. I mean psoriatics are unhealthy people so you can't do it there because the comorbidities kill it. But vitiligo, you don't really have comorbidities. It's a very clean population group. You're just treating them with uvb. And their initial analysis, they looked at people that got a bit of uvb, then a bit more than a bit more and looked at lifespan. But the problem, there's what's called a mortal time bias. You have to live a long time to get lots of uvb. So you know, it's. You reverse the argument. And the other reviewer and I went, no, no, no, you can't, you can't analyze it like this. Go and do a case control, look at people that have lots of. Versus steroids and just do that. And they, and a couple of iterations and you know, we were all lined up. The paper got better and better. Every time I have been earmarked to write an editorial on it and the jid, we were all lined up, the paper was great. And the authors thought, oh no, they're sending it back, they don't want it. And they sent it to a lower ranked journal. I won't look up the journal yourself. And what I would say to anybody out there writing papers is the reviewers are often on your side. If they're saying something. Yeah. If they're saying something when I don't like it, they want to make it better. And that paper's a damn good paper because I didn't. Yes.
- [26:41]
A
All right, so wait, let's finish this. So twice a week, you think that's enough?
- [26:48]
D
So, so look, so I don't. The answer is I don't know What I would say is don't get. But, but it's interesting. So look, we use UVB to treat inflammatory skin disease. You know, psoriasis, bit of X ray. It's a great treatment for inflammatory skin disease. My strong suspicion also based on work I'm doing at the moment is that actually it may well be a systemic anti inflammatory treatment and actually probably far more important than just an inflammatory skin disease treatment. So yeah, I think we're talking about that vitiligo study and wasn't it fascinating when you combine the Barry with the phototherapy, then you get the benefits and I mean so yeah, I think lots of.
- [27:31]
B
All right, just about like the level of exposure. So I like the vitamin D as a biomarker of UV exposure. Interestingly, I think it was nhis, but it was like from one of the health interview studies where they all said labs they looked and you know, people's reported sunscreen use and shade seeking behavior did not correlate with their vitamin D levels. So I guess one question is, can you still get, you know, beneficial exposure while still using some kind of shade seeking, like in some kind of sunscreen level that would prevent or reduce your risk of skin cancer specifically?
- [28:12]
D
Yeah, look, don't get sunburned is the, is the important message. I have to say. We've done some unpublished work where we showed that, you know, factor 50 SPF 50 sunscreen blocks no release. And that is more of a concern to me. I mean, that's a concern to me. The truth is we know that patients don't put enough sunscreen on, you know, so, you know, the SPF 50 is a, is a theoretical lab test. There's no relation to the SPF when it's applied. So I think sunscreen can be better than it is, I suppose.
- [28:43]
A
All right, Patton, what do you. So Tim is often our biggest skeptic of anything, so I. But maybe we got you already, Pat. And what's. What, what do you got?
- [28:53]
C
Oh, I, I am maybe skeptical on both sides. I think that, you know, the shield yourself from the sun, things like that. I think that's a bit much. I did, you know, in reading some of your, your papers and some of the references that you mentioned, I wound up chasing down this one paper, American Journal of Epidemiology 2013. And it was prospective study of UV radiation exposure and mortality risk in the United States where they actually, I mean, you know, they set their definition of how they were defining who got more UV versus less. But the patients who seem to get more UV by The way that they determined it actually had worse cardiovascular mortality. What was your comment on that? Did they not really look at what, like UV exposure?
- [29:47]
D
Yeah, look. So that's the. That's the only paper I've looked. I've looked really hard for papers on sun exposure. That is the only one I found.
- [29:55]
A
The one article in the world ever.
- [30:00]
D
And basically what they found was that people in Louisiana die more than people in New Jersey because they compared, I think, six states. Um, but what was interesting was the mortality was not cancer. The big cause of mortality was respiratory disease. Now, if we're saying that cancer's UV's great danger is melanoma, that's what we expect. Not at all. The big killer was you're far more likely to die of respiratory disease in Louisiana than you are in, you know, Ohio, Pennsylvania, and there were New England states. And actually the deaths from cancer. No increase in deaths from cancer in women, largely increased in men, but it was liver cancer. So, you know, so it's an observational study full of all the problems you have with observational studies. However, America's different. You know, you guys live a way lot further south than we do. New England is the same latitude as the Mediterranean coast of France. The Cote d', Azur, Florida is the same latitude as the Sahara Desert. So, you know, you guys live in a different UV environment. To us, white skin is very. Is not, you know, skin color. White skin in Europe and in China has evolved as an adaptation to the lack of sunlight there. It is not the skin color adapted to an American environment, particularly in the south of America. So, you know, maybe there is a difference there, but the data is not nearly as good as our biobank data. You mentioned the biobank study. We did. I mean, I was actually one of the subjects. Half a million subjects. The assessment at the start took three hours and it took three years for the assessment group to move around Britain recruiting these 500,000 people a mass. Hundreds of questions in the questionnaire, all sorts of measurements, and of course it's then linked in. We have a universal health service here. Everybody's records go into the same health service. Same death outcomes, same health outcomes, same cancer outcomes. We have incredibly robust data here for these population studies in. In Britain and in Scandinavia because we have these universal health services. And the. We adjusted that very carefully for the confounders that the sunbed use. We didn't call it sunbed. Yes, we call them sun seekers because we were looking at sunbed users as a behavioral marker because we know that behaviorally People that use sun beds seek the sun more, they sunbathe more, they expose more of their, you know, more of their skin to the sun. So that was really, we wanted a behavioral mark of a sunny dysplasia rather than. And as I always say to journalists, I am not saying sun beds make you live longer. This is an observational study. You need an interventional study to give causation. I am saying that sun seekers live longer. So there is something about being a sun seeker.
- [33:14]
A
So what do you tell? So patient, normal patient comes in, you know, they've got, you know, six moles that look a little funny but nothing terrible. They've got maybe an AK or two but haven't had skin cancer yet. So normal to low risk patient. What I want to hear what you tell them and then let's take a cardiac transplant patient who's had, you know, nine squames and two melanomas. Does your, does your what?
- [33:46]
D
What do you tell? They're com. They're completely different people. So your bog standard, Brit. Get some, don't get burnt, get sunshine. You know, we, we have. What's really interesting is this whole evolutionary thing how. What's fascinating is that white, pale skin has independently evolved in humans who move to low light areas. So the genetic variants leading to pale skin in China, predominantly there's about 20, 20, 25 genes affecting skin pigmentation, but it's three or four big ones. So independently kit LG, predominantly white skins evolved in people who moved to China. And independently white skin has evolved in people who moved to Europe, predominantly SLC 45A2. The point is humans who move to low light environments repeatedly and independently evolve pale skin to make up for the lack of sunshine. Because what skin color does is it determines your risk to sunshine. So as a day Adamson shows beautifully in America. If you've got dark skin in America, you have no risk of UV induced skin cancer. I've been working in Ethiopia on and off for the last 14, 15 years. My colleagues there and I've spent about nine months there. I suppose we see no UV induced melanoma, no UV induced STCs. Sure we see atrial melanomas, sure we see marginous ulcers. Those are not UV ones. So you have no risk of UV induced skin cancers if you've got dark skin. But the big things that kill black Americans are the blood pressure ones. Blood pressure is higher with it, stroke with it, heart disease. That is what kills black Americans. And you need far more UV to get that healthy fall and blood pressure. If You've got dark skin. And we are putting out this one size fits all message and it's, it's wrong.
- [35:45]
C
Do you like the, the, the Australian, like the new guidelines they put out last year or do you think even.
- [35:52]
D
Yeah, it's. So I think they're being a bit cautious. I mean, I know them all well. I'm Rachel Neal, who's the first author's coming to stay with me in August. And so, you know, I know those guidelines well. Yeah, so they've said get in. They've said sunlight's got health benefits. We need to think about that. And they've said skin color absolutely determines your response. I used to work in Australia as well. I was, I did internal medicine there 30 years ago and a bit of work for flying doctor service. Again, Aboriginal Australians, the original Australians have no UV induced skin cancer. They've been there for 60,000 years. They have a skin adapted to a, the UV environment. The, the message is for white Europeans who arrived there when we couldn't send convicts to the Americas, we shipped them off to Australia when you guys left. And so, and we had this, I have to say in Britain we have this. And of course they've got this, you know, slip, slap, slot, the whole uv that is for white Europeans in a real high UV environment. So I was a, an internal medicine kind of middle grade doctor in cairns in Queensland 30 years ago. And in Cairns, mid winter June, the UV index in the middle of the day is 7 for, for about an hour. In mid summer, the UV index is, is 14. So in, in Britain, in Scotland we copy the Australian sunlight, slip, slap, slot guidance. If you're out between 11 and three, you know, put on sunscreen. So last year the UV index in Scotland is that. No. Tim, how many weeks do you think the UV index hit? 7 in Scotland last year?
- [37:40]
C
Just throwing this, I'm gonna say eight weeks.
- [37:44]
D
Okay, well, Laura, any idea you maybe you don't know Scotland how you the sense. Okay, so it was the 24th of June, five minutes. Just after lunch.
- [37:57]
A
Just after lunch.
- [37:58]
D
And yeah. And yeah.
- [38:00]
C
Wow. And yeah, so I was close.
- [38:03]
D
The year before it was 10 minutes. The year before it was 10 minutes. So. And yet we copy the Australian slips up. Madness. It is madness.
- [38:17]
A
Well, Doctor, I want to thank you. So this has been so much fun and so hopefully enlightening for lots of our colleagues to at least start to think about this and think about, you know, baking your melanoma patient feel like they should never go outside again because that's often what we end up making them. Making these patients feel like. So I really enjoy, really enjoyed the discussion today, and I want to invite you to stay around while we move on to our trivia section. So the rules that Dr. Patton has set, we have to let him finish the question, and then as soon as he finishes the question, you just can shout out whatever. If you think you know the answer, shout it out. But you got to let them finish.
- [39:05]
C
All right, you guys ready? These are UV related trivia. All right. In what year did Hawaii's sunscreen ban targeting oxybenzone and octinoxate officially take effect?
- [39:18]
B
2018.
- [39:20]
A
2020.
- [39:22]
D
Recently. 2020 is my guess.
- [39:24]
A
I'm gonna go with 20. 2019.
- [39:26]
C
Then it was 2021. 2018 was when the. The law was passed, but they gave everybody two years. And Matt, you were just in Hawaii. Are there SWAT teams at the airport and on the beach confiscating sunscreens and stuff?
- [39:44]
A
You know what? I. I saw a lot of shady looking characters, but I wasn't sure what they. That's probably it.
- [39:51]
C
There's a whole black market. I'm sure. Right. All right, number two, which form of cutaneous tuberculosis did Niels Ryberg Finson successfully treat with concentrated light radiation leading to his Nobel Prize in 1903?
- [40:09]
D
Lupus miliary.
- [40:13]
C
It was lupus vulgaris. How would you treat those? Those patients are on death. It was Lucas Vulgaris.
- [40:20]
D
With a bronchoscope. With a bronchoscope. You just get in there and pour the UV in. Yeah.
- [40:26]
C
That was how Trump was going to fight Covid.
- [40:28]
D
I think that's the beach. It's going to work.
- [40:31]
A
Hey, there's. I'm not. It's a long dive, but there is very good evidence that UV substantially reduces your risk of COVID death. And Director Weller's done a fair amount of that work.
- [40:41]
C
No, no, I was watching another interview with Dr. Weller where he went over that data. Pretty interesting.
- [40:47]
D
Yeah.
- [40:48]
C
Okay. Yes, it was lupus vulgaris. We used to derms, used to win Nobel prizes, and now we sell 300 skincare lines. All right, number three, which popular sunscreen brand was created by World War II Airman Benjamin Green, who added coconut oil and cocoa butter to red veterinary petroleum?
- [41:08]
A
Copper tone.
- [41:11]
C
It was coppertone. That was a little bit of a tie between. Dr. Miller.
- [41:15]
D
Man.
- [41:16]
A
I'm taking it. I'm taking it. I got fair.
- [41:19]
D
It was the transatlantic link. I was there first. I really was.
- [41:24]
C
Exactly. That's why I'm giving you the benefit of the.
- [41:30]
D
Trading. Like on a trading floor. You Want your computer just next to the data hub because it gives you a millisecond lead.
- [41:39]
A
All right, well, Dr. Weller, thank you so much. This has been so much fun. And I'm certainly expecting we'll be having you on again in the future as this story continues to develop, because it's, it is fun to talk about.
- [41:52]
D
Well, thank you. I really enjoyed it. I hope to see you guys at the aad, perhaps.
- [41:56]
B
Yes, that would be great.
- [41:57]
C
We'll all be there.
- [41:58]
A
Yep. All right, well, let's, let's move on to the little three. So these are three more articles that we thought were important. There are three more topics, but not quite as important as the big three. I'm going to start us off and really I'm going to do three very three articles that are all very quick. So number one was that if you got immune checkpoint inhibitor induced rash and then you got dupilumab, your survival was better than if you didn't get an immune checkpoint inhibitor rash or if you got one but did not get dupilumab. Main takeaway from the article that the authors had was dupilumab works well for immune chicken point inhibitor rashes without making prognosis worse. My takeaway is it makes prognosis better by stimulating your IL4 system, but that's a pretty big jump. Second one was about the cardiometabolic safety of dupilumab. So this was a large database study in which it compared people on DUPY for AD to people on methotrexate for AD and people on DUPY for AD to people on cyclosporine with ad. And the main takeaway was that the cardiovascular risks were a little bit lower for the people on dupy. The main important thing here is I've always been a little concerned that blocking IL13 might increase cardiovascular risk because we know that coronary plaque macrophages are inhibited by IL13, so maybe blocking it increased cardiovascular risk. This seemed to not show that. And so there were a few that were even statistically significantly decreased. But I, you know, they were, I don't think it was multiplicity controlled and all that. But then the third one was dupilumab and neuropsychiatric outcomes in little kids. And it's kind of exactly what you would think all psychiatry, once you go on dupy, your risk of getting any psychiatric disorder as a child is cut by almost 50%. Specifically, neurodevelopmental and behavioral disorders, mood disorders, anxiety disorders, sleep disorders, learning disabilities were actually cut the most. And then for negative controls to make sure it wasn't just some weird, you're getting more care or something like that. They showed that accidental injury was not affected by dupilumab use. And they showed that conjunctivitis increased with dupilumab use. So just a bunch of data that three different articles all looking at either ancillary benefits or lacks of harm with dupy. You know, I don't know. Is there anything super interesting that you guys want to comment on that?
- [44:41]
B
I guess we don't have disclosure portion of this podcast.
- [44:45]
A
I get paid a lot of money, God damn it. Because I get. I'm dis.
- [44:52]
C
Do you not give enough talks for doopie?
- [44:54]
A
Like you're.
- [44:54]
C
This is a big lobbying thing. No. Great. We love doopie, I'm sure.
- [44:59]
D
Yeah. All right.
- [45:01]
B
It may be that people with bad immunotherapy rashes are more likely to get doopie and the more cutaneous immune related adverse events more severe, associated with better.
- [45:12]
D
Yeah.
- [45:13]
B
Cancer survival. And I was putting that out there. It also may be that duping saves. Yes. I'm not gonna. All right, I'll go on to the next.
- [45:21]
A
All right. All right.
- [45:22]
B
Okay. So this is a little bit of follow up to sort of what do you do with patients on biologics? Do you switch between classes? Do you stay within the class? Last week we talked about a paper, you know, looking at people who moved from one IL23 inhibitor to another, showing that they, you know, in general had a pretty good response. So this was a J eadv nam and this is out of sole and comparative analysis of switching basically between IL23A and IL17. This wasn't a huge study. There were basically. And they compared them to patients who were starting naive. And so most people. Most common biologic was about half of patients were on risankizumab, about a third on gselkumab and about 3, 17, 18% on ixekizumab. Most people, they just were not switching and then basically like 21 switched intraclass and then 22 switched interclass. And so what you can see here is that basically the patients who switched between classes were more likely to reach a PASI 90 or PASI 100 response than the patients who switched to another drug within their. Within their same class. So, you know, I think it. It's sort of. It doesn't detract from what we saw before. I also still think you have pretty good darn good PASI responses even if you stay on an aisle 23. But some data that if you really are looking for improvement, you're more likely to get it when you switch mechanisms first.
- [46:59]
A
Did it matter? And I know they were small numbers. Did IL23 to IL17 work just as well as IL17 to IL23?
- [47:10]
B
That's a good question. I don't think they dissected it out like that enough to be able to tell, but basically somebody else read that and saw better.
- [47:18]
A
So the takeaway that I now have is intraclass switching can work, but it's a higher probability that inter class switching is going to work.
- [47:28]
B
That is correct.
- [47:29]
C
I think we talked last week like, we like aisle 23s. And so if somebody was failing Rizan Kizumab, would you switch. Switch them up to the other 23.
- [47:40]
A
Trim fire. Damn it, Patton, use the grand name.
- [47:43]
C
And I think we all kind of said back then, probably stick with trim 5 because we like the 23s. Does it. Would this change anything or would you kind of have that conversation with the patient? Like, look, there's data that suggests you really want to get that really, really good Pasi score. Let's switch you over to 17, I would say.
- [48:04]
B
And again, like, nobody had less than a Pasi 75 response.
- [48:08]
C
Yeah.
- [48:08]
B
Okay, so these weren't like bad non responders. I would still go to one more aisle 23. If that didn't work, I go to an aisle 17. If they're on an aisle 17, I'd say, let's go to an aisle 23. Just because I like the efficacy, safety, blah, blah, blah.
- [48:22]
C
We still heart, aisle 23s.
- [48:25]
B
Yep. Heart.
- [48:26]
A
They just say they're just safer.
- [48:29]
B
Exactly.
- [48:30]
C
All right.
- [48:31]
A
Had you.
- [48:33]
D
What?
- [48:34]
A
Nothing. Nothing. You don't do any drug talks. I forget how pure you are.
- [48:37]
C
Okay, well, I wouldn't go that far, but I mean, that's fine. My little three paper was from 2024. Jamaderm. No, 2025.
- [48:48]
A
2025.
- [48:50]
D
Yeah.
- [48:50]
C
Gunter et al titled C reactive protein in response to adalima patients with high hydradinitis separativa. Post hoc analysis of two randomized controlled trials. So they looked at the data from the Pioneer 1 and Pioneer 2 that compared adalimumab versus placebo in patients with moderate to severe HS. And they wanted to see if CRP levels were associated with responses. And they put all the data in Table 2, which was a totally confusing table. I feel bad. I called Ferris on Saturday. I'm like, I don't. I literally don't understand these numbers. They're all over the place.
- [49:27]
A
The point being adeliminal residencies Just like resident. You don't understand Jacquard Ferris.
- [49:32]
C
Exactly. Elevate overall elevated CRP associated with lower odds ratio of clinical response. Adalimumab had a higher odds ratio of clinical response compared to placebo in both CRP high and normal CRP patients. And then the higher the crp, the reduced odds odds ratio of clinical response. I don't know what to take away from this paper. I didn't think it was terribly useful. I mean, if you had higher BMI and more severe cutaneous disease, you had higher crp. So basically worse disease is going to be less responsive to adalimumab. I don't think that's a huge surprise. I don't know if this helps us manage these patients at all.
- [50:15]
A
Yeah, I was hoping it was going to be something like, if their CRP is this high, then you should use it. But no, it was basically, it's more, the higher their crp, the worse their disease. Like that was.
- [50:26]
B
It's a marker of bad disease and high CRP patients just aren't as likely to respond. But it's still better to put them on adalimumab than placebo. It's not like they're non responders to the drug. They just have worse disease that's harder to treat.
- [50:40]
C
Right. And you kind of, you know that from, you know, your heavier patients, you're like this, this may not work. We might have to bump up the dose or try and go to infliximab, which is weight based dosing. And the more severe disease, you're kind of like, I don't know if how well adalumumab is going to work. So it was almost like a reflection of the patients that you know are going to be harder to treat, but that doesn't stop you from, from treating them.
- [51:03]
A
Yeah. All right, we're going to jump on to our next segment. The Baby three. These are all three supposed to be quick hitters. My first one was looking at pregabalin versus gabapentin for itch. And here's what was interesting. They work the same for each improvement. Maybe, maybe that gabapentin was a little bit even better for itch improvement according to the 5D pruritus scale. But for DLQI, it really looked like gabapentin was better. And that was primarily because pregabalin caused more dizziness. And it's a real issue with these drugs, pregabalin and gabapentin. I rarely use any of them anymore because there's now data that they increase the Risk of hip fractures in elderly patients because of falls. So I use mirtazapine almost all the time. I rarely use gabapentin because of dizziness and feeling like a zombie. Anything different, anything else you guys would take from that? Just that it kind of confirmed for me lots of dizziness and, and that kind of side effect with these drugs.
- [52:11]
B
I never use pregabalin, so I mean rarely. Gabapentin, some Mirtaz. I agree. Mirtazapine, it also makes people more hungry so they put on weight.
- [52:20]
A
But that's which is often good for old people.
- [52:22]
C
Patton, I use gabapentin all the time.
- [52:26]
A
Have you ever used mirtazapine?
- [52:29]
C
I have, but it's usually in patients that fail gabapentin and I've not had had great results with it.
- [52:37]
A
It's much easier to use in gabapentin.
- [52:40]
C
15Mg QHS, probably a habit thing. The hip fracture thing is definitely something I'm going to think about more.
- [52:48]
D
Yeah.
- [52:49]
A
All right, let's go on to our next one. Let's see here. I think this is Ferris.
- [52:55]
B
Yeah. Risk. This is risk of different subtypes of psoriasis following an episode of gut test psoriasis. This is Creedin et al from Lubeck. And so this was a Trinetics database study. Basically you follow patients who were diagnosed, never had a psoriasis diagnosis, diagnosed with guttate psoriasis between 2003 and 23 and then looked at their lifetime risk of developing psoriasis. Turns out that about a 12.5% lifetime risk of getting plaque psoriasis, 7.7 for psoriatic arthritis and then around 2.9 for like GPP, pulmoplantar, pustulosis, nail erythrodermic. Most of that risk seems to be in the first one or one to five or zero to five years after their gutate diagnosis. So previous estimates were like 25%. This was lower. But this is probably more rigorous and less bias than previous studies.
- [53:56]
A
So useful thing to be able to say to people, 80% chance this is going to be a one time thing and go away. 20% chance that it's going to come, you're going to get something like this back.
- [54:05]
B
I really only like at most a 12 and a half percent chance.
- [54:07]
A
So Patton, what do you, what do you, what do you do when you see gutate psoriasis? Shot of kenalog, some amoxicillin, what do you, you know, methotrexate, what do you, if they got bad gutate that you need to do something with.
- [54:21]
C
I'll see if they can come in and get the light box. Topical tack. Who knows, maybe I'd give them a sample of Bemzalex. Right. That's going to be a one time shot. They'll be clear.
- [54:33]
A
Do you get my Moxis, Ferris? Do, do you empirically give people Moxicillin?
- [54:37]
B
I don't, I don't know if, I mean, if they had a, you know, strap. Yeah, yeah, I don't. I, you know, I try. I agree. If they could do narrowband. I like narrowband. I'll try to kind of hit them with like methotrexate even sometimes just as we can do for, you know, three to six months and then try to take them off. So.
- [54:54]
A
Okay, do you guys check, do you send them to urgent care or somewhere to get a strep test?
- [55:00]
D
No. No.
- [55:01]
A
Okay. Interesting. All right, let's, let's finish it up. So Patton, what's our last one?
- [55:08]
C
Yeah, you know what, I didn't write down the journal in the, the author.
- [55:13]
A
I think it was in Durham. I think it was in Durham.
- [55:15]
D
Scottish.
- [55:17]
A
Yeah, let me see here. It was comparison of infection rate between steroid on sterile gloves during MOHS updated systemic review and meta analysis. Sardo et al. Journal of Cutaneous Medicine and Surgery.
- [55:28]
C
Thank you. Thank you. So meta analysis, four studies, about 3,000 Mohs cases with non sterile gloves. Infection rate was 2%. About 7,500 Mohs cases with sterile gloves. Infection rate was 3.1. Essentially no difference. And non sterile gloves are 10 times cheaper. So I am taking this data to my chair and I'll take a cut of how much money we save and I will be rich beyond my wildest dreams. I can't wait.
- [55:54]
B
I think it was, did you say that? The opposite. Non sterile, 3.1 sterile.
- [55:59]
D
Right.
- [55:59]
A
So, no, it was a lower rate of infection with the non sterile glove.
- [56:02]
B
It was a higher rate. Okay.
- [56:04]
C
Yeah, it was, you know, statistically insignificant, but yeah, technically it was 2% versus 3.1.
- [56:11]
B
Okay. Yeah, so I, the only thing I would say when I see these is Mohs is almost all on the head and neck. It's really rare to get infections, you know, is it different if you're looking at the lower leg?
- [56:23]
C
I learned that Ferris essentially puts her people in like a bubble, like bubble boy. He's like, you will not get infected. Stay in your bubble for two weeks.
- [56:34]
A
Don't touch it. Don't talk to your kids, Stay away from your pets.
- [56:37]
B
Exactly.
- [56:38]
A
There's a month off work. Lmfa I mean, you know, I, yeah.
- [56:44]
C
I, you probably don't need to do the sterile gloves. But I think it's a good point that Ferris brings up. The Mohs on the head and neck, they, they don't get infected. Lower leg, trunk. I mean, I don't, I, I don't think those infections come from the gloves. Right. I mean, I, no, you're right.
- [57:00]
B
I think they come from wound care.
- [57:01]
C
Using. My takeaway is using sterile gloves for the stuff that we do actually probably doesn't make sense. And it is expensive.
- [57:08]
A
Yeah, I could say it's like 2 bucks a surgery. Pair of sterile gloves is like 225. Pair of non sterile gloves is like a quarter. They're not even a quarter. Pair of non steroid gloves, like 3 cents. What am I talking about?
- [57:19]
C
10 times cheaper.
- [57:20]
D
Yeah.
- [57:21]
A
All right. So want to thank everybody for joining us today. This was a really fun episode. Next week we are going to have on Dr. Jakob Thyssen from Denmark. So we're continuing our very hoity toity tour of people doing cool stuff in Europe.
- [57:39]
C
I will badmouth Europeans last week. You're lucky we still have an audience.
- [57:47]
A
And I have to admit something. So I will actually openly admit in eczema. So I, I believe in my heart of hearts that I'm the smartest person in the world when it comes to. I know that's not true, but I still believe it. Jacob, this is smarter than I am, knows more than I am. I literally, if we're gonna be talking about a hand XM in particular, I cannot wait to hear what he's got to say. I think there's gonna be some really cool stuff. But so I want to again thank everybody for joining us today. You know, derms on drugs. Well, thank you. And, and if by, if you got questions, comments or ideas for topics you wish cover on the show, shoot us an email@questionsurmsondrugs.com and I hope you learned a few things. I hope you laughed a few times. And mostly I hope you plan to join us next week. Until then, I'm Matt Zyrus.
- [58:39]
C
I'm Tim Patton.
- [58:40]
B
And I'm Laura Farris. And we are derms on drug.